A TEXTBOOK OF ORGANIC CHEMISTRY* The English Translation from the German of A. BERNTHSEN, Ph.D. EDITED AND REVISED tO DATE BY J. J. SUDBOROUGH, Ph.D., D.Sc., F.I.C. Professor of Organic Chemistry in the Indian Institute of Science, Bangalore NEW YORK D. VAN NOSTRAND COMPANY EIGHT WARREN STREET PREFACE The present edition is on much the same lines as the former, but contains the following new chapters: XL VIII. Fermen- tation and Enzyme Action ; XLIX. Catalytic Action of Finely- divided Metals and Metallic Oxides; L. Unsaturation; LI. Ali- phatic Diazo- and Triazo-compounds. The Chapters on Alkaloids, Terpenes and Camphors, and Proteins have been rewritten. The earlier Chapters give an outline of General Systematic Organic Chemistry, and the later ones deal in somewhat more detail with some of the problems which have attracted a considerable amount of attention within recent years. Numerous references to original papers are given in the text, and the following works are recommended for special study : Meyer and Jacobson. Handbuch der organischen Chemie. Lassar-Cohn. Arbeitsmethoden. Th. Weyl. Die Methoden der organischen Chemie. Werner. Lehrbuch der Stereochemie. Landolt. Das optische Drehungsvermogen. 0. Aschan. Chemie der alicydischen Verbindungen, E. Fischer. Aminosduren und Polypeptide, 1906. Do. Purin Gruppe, 1907. Do. Kohlenhydrate und Fermente, 1909. Cain. The Diazo-compounds. Smiles. Relations between Chemical Constitution and Physical Properties. iii IV PREFACE Stewart. Stereo-chemistry. Do. Eecent Advances in Organic Chemistry. Sidgwick. Organic Chemistry of Nitrogen. Harden. Alcoholic Fermentation. E. F. Armstrong. Simple Carbohydrates and Glucosides. Bayliss. Enzyme Action. Schryver. Proteins. Valuable Summaries of certain fields of Organic Work, such as Combustion, Diazo-compounds, Grignard's Reagents, Cam- phor, Tautomerism, Stereo-chemistry of Nitrogen, &c., will be found in the Reports of the British Association since 1900, and also in Ahren's Sammlung chemischer und chem.-technischer Vortmge from 1897 onwards. J. J. SUDBOROUGH. BANGALORE, March, 1912. ABBEEVIATIONS A. = Liebig's Annalen der Chemie. Abs. = Journal of the Chemical Society. Abstracts. Am. = American Chemical Journal. Annales Annales de Chemie et de Physique. Arch. f. Phys. = Archivfur Physiologic. B. = Berichte der deutschen Chemischen Cfesellschaft. B. A. Rep. = British Association Report. Bull. Soc. Chirn. = Bulletin de la Socitte Chimique a Paris. C. C. = Chemisches Central-Uatt. C. R. = Comptes rendus de I' Academic des Sciences. J. A. C. S. = Journal of the American Chemical Society. J. C. S. = Journal of the Chemical Society. Transactions. J. Ind. = Journal of the Society of Chemical Industry. J. pr. = Journal fur praktische Chemie. M. = Monatshefte fiir Chemie (Wien). P. = Proceedings of the Chemical Society. Phil. Mag. = Philosophical Magazine. Rec. = Recueil des Travaux Chimiques des Pays Bas. S. J. = Sudborough and James's Practical Organic Chemistry. Walker, Phys. Chem. = James Walker's Introduction to Physical Chemistry. Zeit. phys. = Zeitschrift fiir physikalische Chemie. n = normal. 0-ether = Oxygen ether. N-ether = Nitrogen ether. B.-pt. = Boiling-point. M.-pt. = Melting-point. d = dextro. I = Isevo. r = racemic. = symmetrical. i = inactive. R = alkyl radical. Me = Methyl, CH 3 . Et = Ethyl, C 2 H 6 . Ph = Phenyl, C 6 H 6 . o = ortho. m = meta. p = para. TABLE OF CONTENTS INTRODUCTION Page Qualitative Analysis ...-..-. 2 Quantitative Analysis - 4 Calculation of the Empirical Formula - .... 7 Determination of Molecular Weight - - 7 Polymerism and Isomerism - 12 Chemical Theories - - - 13 Explanation of Isomerism; Determination of the Constitution of Organic Compounds 16 Rational Formulae - - 19 The Nature of the Carbon Atom 19 Homology ........ ... - 20 Radicals - - 22 Classification of Hydrocarbons Physical Properties of Organic Compounds - - - - 21 CLASS I. ALIPHATIC OR OPEN -CHAIN COMPOUNDS i. HYDROCARBONS - - . 30 A. Saturated Hydrocarbons, C n H2n +2 30 B. Olefines, CnH^ - 42 c. Acetylene Series, C n H 2n -2 ... 49 D. Hydrocarbons, C n H 2n -6 * " ^3 ii. HALOID SUBSTITUTION PRODUCTS OF THE HYDROCARBONS - 54 A. Halogen Derivatives of the Paraffins - - - 54 B. Halide Derivatives of Unsaturated Hydrocarbons - - 64 vii vili CONTENTS Page in. MONOHYDRIC ALCOHOLS OK ALKYL HYDROXIDES 65 A. Monohydric Saturated Alcohols, C n H 2n+1 OH - - 66 B. Monohydric Unsaturated Alcohols, C n H 2 n_iOH - - 81 C. Monohydric Unsaturated Alcohols, C n H 2n _3OH - - 82 iv. DERIVATIVES OF THE ALCOHOLS 83 A. Ethers Proper or Alkyl Oxides 83 B. Thio-alcohols and Thio-ethers 87 c. Esters of the Alcohols with Inorganic Acids, and their Isomers 91 Esters of Nitric Acid 93 Derivatives of Nitrous Acid 94 Esters of Sulphuric Acid 98 Derivatives of Sulphurous Acid 99 Alkyl Derivatives of Hydrocyanic Acid - - - 101 D. Amines or Nitrogen Bases of the Alkyl Radicals - - 104 Hydroxylamines, Hydrazines - - - - - 111 E. Alkyl Derivatives of Phosphorus, Arsenic, &c. - - 113 F. Organo -metallic Compounds 118 v. ALDEHYDES AND KETONES - - 121 A. Aldehydes 122 B. Ketones 131 Aldoximes and Ketoximes - - - = - - 137 vi. MONOBASIC FATTY ACIDS 139 A. Saturated Acids, C n H 2n O 2 '- - - - 139 B. Unsaturated Acids, C n H 2n -zO-2 - - 161 C. Propiolic Acid Series, C n H 2n - 4 O2 - - 166 D. Halogen Substitution Products of the Monobasic Acids - 167 vii. ACID DERIVATIVES - - - .-**,- . - 171 A. Esters of the Fatty Acids ,;. -r V r ! - - - 172 B. Acid Chlorides, Bromides, &c. - /. ' ,?* , -- ' * " 178 C. Acid Anhydrides - ; w j ;. . - - 180 D. Thio-acids and Thio-anhydrides - .. * - - 181 E. Acid Amides and Hydrazides - - - 182 F. Amido- and Imido-chlorides - 185 G. Thiamides and Imido-thio-ethers - - 186 H. Amidines and Amidoximes - . -c - ; - - - 187 CONTENTS IX Page VIII. POLYHTDRIC ALCOHOLS- . ; "iJ .'* r ' ^'i-.-'n^' S .*;;.!/.. ,': 188 A. Dihydric Alcohols or Glycols '.-' i ; "v^.,/.^.-..! . jgg B. Trihydric Alcohols *' '' ''. - ''"''"" - :< ' '' - 19 ? c. Tetra-, Penta-, and Hexahydric Alcohols - - 201 ix. HYDROXY MONOBASIC ACIDS AND COMPOUNDS RELATED TO THEM ... - '''--''''-' v^- r.>' : -$ >. . 205 A. Monohydroxy Fatty Acids - - '' '"'-'-**"' - 205 B. Polyhydric Monobasic Acids 218 c. Hydroxy-aldehydes - - ->~n --4MO- - 220 D. Dialdehydes ' i j " : ^ /ij s;- )L> , ' ^ - ' - - 221 E. Diketones - - ...... - - - 221 p. Aldehydic Monobasic Acids 222 G. Monobasic Ketonic Acids 222 x. DIBASIC ACIDS - ' - 231 A. Saturated Dibasic Acids, or Oxalic Series - - 231 B. Unsaturated Dibasic Acids 241 C. Hydroxy Dibasic Acids 247 D. Dihydroxy Dibasic Acids .... - 249 Stereo-isomerism of the Tartaric Acids - - - 250 E. Polyhydroxy Dibasic Acids .... - 259 p. Dibasic Ketonic Acids ..-.-.- 260 xi. POLYBASIO ACIDS 261 A. Saturated and Unsaturated Polybasic Acids - - - 261 B. Hydroxy Polybasic Acids 262 xii. CYANOGEN COMPOUNDS - - - - - - 263 A. Cyanogen and Hydrocyanic Acid 266 B. Halogen Compounds of Cyanogen 272 C. Cyanic and Cyanuric Acids - - 273 D. Thiocyanic Acid and its Derivatives .... 275 E. Cyanamide and its Derivatives - - 277 xin. CARBONIC ACID DERIVATIVES 279 A. Esters - 279 B. Chlorides - 280 X CONTENTS Page C. Amides, Ureides, Purine Group - - - - - 261 D. Sulphur Derivatives of Carbonic Acid - - - 295 K. Amidines of Carbonic Acid - . . . 297 xiv. CARBOHYDRATES - 298 A. Monosaccharoses 300 B. Di- and Trisaccharoses - - 314 C. Polysaccharoses - 317 CLASS II. CHEMISTRY OF THE CYCLIC COMPOUNDS xv. INTRODUCTION ... 321 CARBOCYCLIC COMPOUNDS XVI. POLYMETHYLENE DERIVATIVES 322 xvii. BENZENE DERIVATIVES Introduction 327 Characteristic Properties of Benzene Derivatives - 328 Isomeric Relations 329 Constitution of Benzene 332 Determination of Positions of Substituents - 337 Occurrence of Benzene Derivatives 340 Formation of Benzene Derivatives, &c. ... 341 xvni. BENZENE HYDROCARBONS 344 A. Homologues of Benzene, C n H2n-6 344 B. Unsaturated Benzene Hydrocarbons .... 353 xix. HALOGEN DERIVATIVES - . '- . " . . - 354 A. Additive Compounds - - .... 354 B. Substituted Derivatives --./-- - - - 354 XX. NlTRO- SUBSTITUTION PRODUCTS OF THE AROMATIC HYDRO- CARBONS - -- '*'/.-''-' ' - - - 359 Nitroso-derivatives ,- - 1 : : ; - - - - 365 xxi. AMINO-DERIVATIVES OR ARYLAMINES - 366 A. Primary Monamines . v ' .. i . . . 367 B. Secondary Monamines 375 c. Tertiary Monamines 377 CONTENDS XI Page Do The Quaternary Bases - - '- ' '='* ; '; - '' * '> ' - - 379 E. Diamines, Triamines, &c. - f '- ; - -'- ' lT3&fi'iiO - - 380 Acyl Derivatives of Arylamines ----- 381 Primary Amines with the Amino-group in the Side Chain 383 XXII. DlAZO- AND AZO-COMPOUNDS ; HYDEAZINES - "' "' ' ' ''-~ 384 A. Diazo-compounds - - - ; : ..- .,..*. " 384 B. Diazo-amino-compounds -- : .- - - 392 C. Azo-compounds and Compounds intermediate between Nitro- and Amino-compounds ._'..'!'. - - 394 D. Hydrazines - - - - -.. ' ' - - - 397 E. Azo-dyes - * - - 399 F. Phosphorus Compounds, &c.; Organo-metallic Derivatives 402 xxiii. AROMATIC SULPHONIO ACIDS- '-''""' '"' '' '"' ^^' > . } . 403 xxiv. PHENOLS -,-- - - 407 A. Monohydric Phenols - - 410 B. Dihydric Phenols - .- -- - - - - 417 c. Trihydric Phenols - - 419 xxv. AROMATIC ALCOHOLS, ALDEHYDES, AND KETONES - - - 421 A. Aromatic Alcohols . - 421 B. Aromatic Aldehydes - - 423 C. Aromatic Ketones - .".... 427 D. Hydroxy or Phenolic Alcohols, Aldehydes, and Ketones 429 E. Quinones 430 F. Quinone Chlorimides, Quinone Aniles, and Anilino- quinones 433 G. Pseudo-phenols. Methylene-quinones - 434 xxvi. AROMATIC ACIDS 435 A. Monobasic Aromatic Acids 442 1. Monobasic Saturated Acids 444 2. Monobasic Unsaturated Acids - - - - 454 3. Saturated Phenolic Acids 456 4. Alcohol- and Keto-acids 461 5. Unsaturated Monobasic Phenolic Acids - - - 463 B. Dibasic Acids ...-.--- 464 c. Polybasic Acids - 470 v PREFACE Stewart. Stereo-chemistry. Do. Recent Advances in Organic Chemistry. Sidgwick. Organic Chemistry of Nitrogen. Harden. Alcoholic Fermentation. E. F. Armstrong. Simple Carbohydrates and Glucosides. Bayliss. Enzyme Action. Schryver. Proteins. Valuable Summaries of certain fields of Organic Work, such as Combustion, Diazo-compounds, Grignard's Eeagents, Cam- phor, Tautomerism, Stereo-chemistry of Nitrogen, &c., will be found in the Reports of the British Association since 1900, and also in Ahren's Sammlung chemischer und chem.-technischer Vortmge from 1897 onwards. J. J, SUDBOROUGH. BANGALOKE, March, 1912. ABBEEVIATIONS A. = Liebig's Annalen der Chemie. Abs. = Journal of the Chemical Society. Abstracts. Am. = American Chemical Journal. Annales = Annales de Chemie et de Physique. Arch. f. Phys. = Archiv filr Physiologic. B. = Berichte der deutschen Chemischen Cfesellschaft. B. A. Rep. = British Association Report. Bull. Soc. China. = Bulletin de la Socie'te' Chimique a Paris. C. C. = Chemisches Central-Uatt. C. R. = Comptes rendus de VAcaddmie des Sciences. J. A. C. S. = Journal of the American Chemical Society. J. C. S. = Journal of the Chemical Society. Transactions. J. Ind. = Journal of the Society of Chemical Industry. J. pr. = Journal filr pralctische Chemie. M. = Monatshefte fur Chemie (Wien). P. = Proceedings of the Chemical Society. Phil. Mag. = Philosophical Magazine. Rec. = Recueil des Travaux Chimiques des Pays Bas. S. J. = Sudborough and James's Practical Organic Chemistry. Walker, Phys. Chem. = James Walker's Introduction to Physical Chemistry. Zeit. phys. = Zeitschrift fur physikalische Chemie. n = normal. 0-ether = Oxygen ether. N-ether = Nitrogen ether. B.-pt. = Boiling-point. M.-pt. = Melting-point. d dextro. I = Isevo. r = racemic. = symmetrical. i inactive. R = alkyl radical. Me = Methyl, CH 3 . Et = Ethyl, C 2 H 6 . Ph = Phenyl, C 6 H 6 . o = ortho. m, = meta. p = para. TABLE OF CONTENTS INTRODUCTION Page Qualitative Analysis - , .. ; ..^r 2 Quantitative Analysis : , - 4 Calculation of the Empirical Formula ir .-...i -,..r- /,,*A 7 Determination of Molecular Weight - - 7 Polymerism and Isomerism ' - <-.if* r, "'O^rfTf " * 12 Chemical Theories - . ,. ?/ ,,j .;,,.- , ; . i ,.'..,. ^ ,.. ; - 13 Explanation of Isomerism; Determination of the Constitution of Organic Compounds 16 Rational Formulae 19 The Nature of the Carbon Atom 19 Homology 20 Radicals 22 Classification of Hydrocarbons 23 Physical Properties of Organic Compounds - - - - -21 CLASS I. ALIPHATIC OR OPEN -CHAIN COMPOUNDS i. HYDROCARBONS - - 30 A. Saturated Hydrocarbons, CnH^+a 30 B. Olefines, C n H2n - 42 c. Acetylene Series, C n H 2 n-2 - 49 D. Hydrocarbons, C n H 2n _ 6 - 53 ii. HALOID SUBSTITUTION PRODUCTS OF THE HYDROCARBONS - 54 A. Halogen Derivatives of the Paraffins - - 54 B. Halide Derivatives of Unsaturated Hydrocarbons - - 64 vii Vlll CONTENTS Page in. MONOHYDEIC ALCOHOLS OK ALKYL HYDROXIDES 65 A. Monohydric Saturated Alcohols, C n H 2n +iOH - - 66 B. Monohydric Unsaturated Alcohols, C n H 2n _iOH - - 81 0. Monohydric Unsaturated Alcohols, CnH^.sOH - - 82 iv. DERIVATIVES OF THE ALCOHOLS ...... 83 A. Ethers Proper or Alkyl Oxides ..... 83 B. Thio-alcohols and Thio-ethers ..... 87 c. Esters of the Alcohols with Inorganic Acids, and their Isomers ......... 91 Esters of Nitric Acid ....... 93 Derivatives of Nitrous Acid ..... 94 Esters of Sulphuric Acid ...... 98 Derivatives of Sulphurous Acid ..... 99 Alkyl Derivatives of Hydrocyanic Acid - - - 101 D. Amines or Nitrogen Bases of the Alkyl Kadicals - - 104 Hydroxylamines, Hydrazines ..... Ill E. Alkyl Derivatives of Phosphorus, Arsenic, &c. - - 113 F. Organo-metallic Compounds ...... 118 v. ALDEHYDES AND KETONES - - ..... 121 A. Aldehydes ......... 122 B. Ketones ......... 131 Aldoximes and Ketoximes - - - - - - 137 vi. MONOBASIC FATTY ACIDS ....... 139 A. Saturated Acids, C n H 2 nO 2 - - - 139 B. Unsaturated Acids, C n H 2n _ 2 O 2 . - 161 C. Propiolic Acid Series, C n H 2n _ 4 O2 - A, *I 1 *.: - 166 D. Halogen Substitution Products of the Monobasic Acids - 167 vn. ACID DERIVATIVES ..... . -171 A. Esters of the Fatty Acids - fr/JI-i -' - - 172 B. Acid Chlorides, Bromides, &c. -.'>.;'* & * '-, - - 178 C. Acid Anhydrides ..... .; ' * . - - 180 D. Thio-acids and Thio-anhydrjdes - .-.- - 181 E. Acid Amides and Hydrazides - - - - - 182 F. Amido- and Imido-chlorides - 185 G. Thiamides and Imido-thio-ethris - 186 H. Amidines and Amidoximes - _-- - 187 CONTENTS IX Page viii. POLYHYDRIC ALCOHOLS- ^ -.qh^'i " . .-?v;r>jtfir. .;..., , iss A. Dihydric Alcohols or Glycols r -. : . 188 B. Trihydric Alcohols - - -V - ' ' - ;s - 197 c. Tetra-, Penta-, and Hexahydric Alcohols - - 201 ix. HYDROXY MONOBASIC ACIDS AND COMPOUNDS RELATED TO THEM - - - - - -' : ''' ; "'-*" '"'^ r i^ r<"4 ' . . 205 A. Monohydroxy Fatty Acids - - -'-*'-.' . 205 B. Polyhydric Monobasic Acids - - - - - - 218 c. Hydroxy-aldehydes - ; ' -~' : '* ' ^ v ->1 ; -.*i'. - - 220 D. Dialdehydes ' 1 ! ' : '. s - : J: ' . . . - - 221 E. Diketones - - - - *.. * r^rnj.^ivy 221 F. Aldehydic Monobasic Acids 222 G. Monobasic Ketonic Acids - ' ' *r' a * t $ ... 222 x. DIBASIC ACIDS - - - - - - - . - - 231 A. Saturated Dibasic Acids, or Oxalic Series - - 231 B. Unsaturated Dibasic Acids 241 C. Hydroxy Dibasic Acids 247 D. Dihydroxy Dibasic Acids .... . 249 Stereo-isomerism of the Tartaric Acids - - - 250 E. Polyhydroxy Dibasic Acids .... - 259 F. Dibasic Ketonic Acids 260 xi. POLYBASIG ACIDS 261 A. Saturated and Unsaturated Polybasic Acids - - - 261 B. Hydroxy Polybasic Acids 262 xn. CYANOGEN COMPOUNDS -....--- 263 A. Cyanogen and Hydrocyanic Acid 266 B. Halogen Compounds of Cyanogen - ... 272 C. Cyanic and Cyanuric Acids ... - 273 D. Thiocyanic Acid and its Derivatives .... 275 E. Cyanamide and its Derivatives ... . 277 xin. CARBONIC ACID DERIVATIVES 279 A. Esters - 279 B. Chlorides 280 X CONTENDS Page c. Amides, Ureides, Purine Group - - - - - 261 D. Sulphur Derivatives of Carbonic Acid - 295 E. Amidines of Carbonic Acid - - - - - 297 xiv. CARBOHYDRATES - 298 A. Monosaccharoses 300 B. Di- and Trisaccharoses - - - - - - 314 c. Polysaccharoses 317 CLASS II. CHEMISTRY OF THE CYCLIC COMPOUNDS xv. INTRODUCTION ... 321 CAEBOCYCLIC COMPOUNDS XVI. POLYMETHTLENE DERIVATIVES .... - 322 xvii. BENZENE DERIVATIVES Introduction ..... 327 Characteristic Properties of Benzene Derivatives - 328 Isomeric Relations 329 Constitution of Benzene .... . 332 Determination of Positions of Substituents - 337 Occurrence of Benzene Derivatives 340 Formation of Benzene Derivatives, &c. - - - 341 xviii. BENZENE HYDROCARBONS 344 A. Homologues of Benzene, C n il2n-6 344 B. Unsaturated Benzene Hydrocarbons .... 353 xix. HALOGEN DERIVATIVES ... .... 354 A. Additive Compounds 354 B. Substituted Derivatives -'..-- - . - 354 XX. NlTRO- SUBSTITUTION PRODUCTS OF THE AROMATIC HYDRO- CARBONS ... . . ,./ ... . . 359 Nitroso-derivatives - - - - - - - 365 xxi. AMINO-DERIVATIVES OR ARYLAMINES - 366 A. Primary Monamines * <.- . 367 B. Secondary Monamines - - -. - - - -375 c. Tertiary Monamines - - - r . -V - - 377 CONTENDS XI Page Do The Quaternary Bases - : "' ':- ' ' '-^:^~i >.;-.'? - - 379 E. Diamines, Triamines, &c. - :; '. - ; ^ - j ;-... ;i<': . . 350 Acyl Derivatives of Arylamines - - - - - 381 Primary Amines with the Amino-group in the Side Chain 383 XXII. DlAZO- AND AZO-COMPOUNDS ; HTDEAZINES - ' ' ; "- L 384 A. Diazo-compounds - - ,, ,._,..._...- -,. - 384 B. Diazo-amino-compounds ^ . 7 r - - - 392 c. Azo-compounds and Compounds intermediate between Nitro- and Amino-compounds - . - ', - - - 394 D. Hydrazines - - - - -_ - ' ''<.', - - 397 E. Azo-dyes - - - ... *^ - - 399 F. Phosphorus Compounds, &c.; Organo -metallic Derivatives 402 xxm. AROMATIC SULPHONIO ACIDS- '''"" '"' ''' " ;"- : ''* ''' 403 xxiv. PHENOLS ..-.... . 407 A. Monohydric Phenols - . Jl * *'*' . . 410 B. Dihydric Phenols - - - :' - - - - 417 c. Trihydric Phenols - - 419 xxv. AROMATIC ALCOHOLS, ALDEHYDES, AND KETONES - - - 421 A. Aromatic Alcohols 421 B. Aromatic Aldehydes 423 c. Aromatic Ketones - - :""''* - 427 D. Hydroxy or Phenolic Alcohols, Aldehydes, and Ketones 429 E. Quinones 430 P. Quinone Chlorimides, Quinone Aniles, and Anilino- quinones 433 G. Pseudo-phenols. Methylene-quinones - 434 xxvi. AROMATIC ACIDS 435 A. Monobasic Aromatic Acids 442 1. Monobasic Saturated Acids 444 2. Monobasic Unsaturated Acida - - - - 454 3. Saturated Phenolic Acids - 456 4. Alcohol- and Keto-acids - - - - 461 5. Unsaturated Monobasic Phenolic Acids - - - 463 B. Dibasic Acids ...---.. 464 c. Polybasic Acids - 470 xii CONTENTS Page xxvu. COMPOUNDS CONTAINING TWO OR MORE BENZENE NUCLEI; DIPHENYL GROUP - 470 XXVIII. DlPHENYL-METHANE GROUP 474 XXIX. DlBENZYL GROUP 477 xxx. TRIPHENYL-METHANE GROUP 480 Triphenyl-methane Dyes 482 1. Amino- and Diamino-triphenyl-methane Group 483 2. Rosaniline Group 484 3. Aurine Group 490 4. Eosin Group - 491 xxxi. COMPOUNDS WITH CONDENSED BENZENE NUCLEI- - 494 Naphthalene Group 494 xxxn. ANTHRACENE AND PHENANTHRENE GROUPS- - 504 A. Anthracene 504 B. Phenanthrene 510 C. Complex Hydrocarbons 512 HETEROCYCLIC COMPOUNDS xxxm. INTRODUCTION - - " - - - - - 513 xxxiv. FURANE GROUP ... - 515 xxxv. COMPOUNDS FORMED BY THE CONDENSATION OF A BENZENE NUCLEUS WITH A FURANE, THIOPHENE, OR PYRROLE RING- - ;-, r- v 'Oi>M';:K. * " 52 Indole Group - 521 Indigo and Related Compounds - - 525 xxxvi. PYRAZOLE GROUP - - / '-. - ': -... 528 A. Pyrazole Group - .;;-.;" J - 528 B. Thiazole Group - 529 XXXVII. SlX-MEMBERED HETEROCYCLIC RlNGS - 530 A. Pyrones ----- 531 B. Pyridine - - - - -. ., r. " ; - 533 CONTENTS Xiii Page XXXVIII. QUINOLINE AND AOBIDINE GROUPS - *41 A. Quinoline Group 541 1. Chromone Group - 541 2. Quinoline and its Derivatives - 542 3. Iso-quinoline - - T^ , ,;; . . 547 B. The Acridine Group - - ^ i * '> X . 547 XXXIX. SlX-MKMBEEED HETEROCYCLIO COMPOUNDS WITH POUK CAB- BON ATOMS IN RING - - 549 The Diasines - - . . . . 550 Phenoxazines and Phenthiazines - ' '" ' - 1 " - 554 XL, ALKALOIDS ..... . 554 A, Alkaloids related to Pyridine - "V 557 B. Bases derived from Quinoline - 558 c. Bases derived from Iso-quinoline - - - 560 D. The Morphine Group - - 564 E. Strychnine Bases 565 F. Solanine Bases - .... 565 XLL TERPENES AND CAMPHORS- ...... 567 A. Open Chain Olefinic Terpenes and Camphors 568 BO Monocyclic Terpenes and Camphors 572 o. Complex Cyclic Terpenes and Camphors - .581 D. Compounds related to Terpenes - - - 589 XLII. RESINS; GLUCOSIDES 591 A. Resins ...... 591 B. Glucosides- .... * =592 XLIII. ALBUMINS; PHYSIOLOGICAL CHEMISTRY - 593 xxiv. REDUCTION 601 A. Nascent Hydrogen ....... 601 B. Other Chemical Methods - - - - - -609 C. Catalytic Reduction 610 D. Electrolytic Reduction - * - - 614 XIV CONTENTS Page XLV. OXIDATION ... * . * 616 A. Permanganate - 618 B. Chromic Acid Derivatives - 620 c. Nitric Acid - >>- 621 D. Sulphuric Acid - ...... 622 B. Peroxides ...... 622 r. Oxygen and Ozone 623 G. Other Oxidizing Agents 625 H. Electrolytic Oxidation - - 626 XLVI. STEREOCHEMISTRY OF SULPHUR, SELENION, TIN, AND NITRO- GEN COMPOUNDS- - - - 627 A. Sulphur Compounds - 628 B. Selenion Compounds - 628 o. Tin Compounds - - 629 D. Silicon Compounds .... . 629 E. Nitrogen Compounds ...... 631 p. Phosphorus Compounds - - - - 634 G. Cobalt Compounds 634 H. Carbon Compounds, with Semicyclic Double Linkings 63$ XLVH. RELATIONSHIPS BETWEEN PHYSICAL PROPERTIES AND CHEMICAL CONSTITUTION - . 635 A. Boiling-point -'-"''.. 635 B. Melting-point ---..-.. 638 0. Molecular Volume - ' ' " J - "'"- 4 - - 639 D. Molecular Refraction - 641 E. Molecular Magnetic Rotation - " - - 644 p. Absorption Spectra - - - .-'."-. . 647 G. Anomalous Electric Absorption - . - . . 655 H. Optical Activity -656 Asymmetric Synthesis - - - .... 660 The Walden Inversion - - 661 1. Electrical Conductivity " - -"--. -663 XLVIIL FEBMENTATION AND ENZYME ACTION a: C- >*:. - - 666 A. Alcoholic Fermentation - - . i .V ; . . 666 B. Enzyme Action . 671 CONTENTS XV Page XLIX. CATALYTIC ACTION OP FINELY -DIVIDED METALS AND METALLIC OXIDES - - 674 Oxidations 674 Dehydration ... - 674 Esterification - > - - 677 Formation of Amines, Thiols, Ketones .... 677 L. UNSATURATION 678 A. Types of Unsaturation 678 B. Properties of Unsaturated Acids as affected by the position of the Double Bond 679 c. Compounds with Conjugate Double Bonds - - - 681 D. Compounds of Di- and Trivalent Carbon - - - 683 Carbon Monoxide - - -' - - - 683 Carbylamines - - - - - - - 684 Metallic Cyanides - - - - - - 684 Keactions of Metallic Cyanides. Formation of Nitriles and Carbylamines - - 685 FulminicAcid ....... 687 Tervalent Carbon : Triphenyl-methyl - - - 690 E. Ketens - 691 P. Unsaturation and Physical Properties - 693 LL ALIPHATIC DIAZO- AND TRIAZO-COMPOUNDS - 694 A. Diazo-compounds ....... 694 B. Triazo-compounds 695 INDEX ...... . * . 697 ORGANIC CHEMISTRY INTRODUCTION Organic Chemistry is the Chemistry of the Carbon Com- pounds. Formerly those compounds which occur in the animal and vegetable worlds were classed under Organic, and those which occur in the mineral world under Inorganic Chemistry, the first to adopt this arrangement having been Ltmfoy in his Cours de Chimie (1675). After the recognition of the fact that all organic substances contain carbon, it was thought that the difference between organic and inorganic compounds could be explained by saying that the latter were capable of preparation in the laboratory, but the former only in the organism, under the influence of a particular force, the life force vis vitalis (Berzelius). But this assumption was rendered untenable when Wohler in 1828 synthetically pre- pared urea, CON 2 H 4 , a typical secretion of the animal organism, from cyanic acid and ammonia, two compounds which were at that time held to be inorganic; and when, shortly afterwards, the synthesis of acetic acid, by the use of carbon, sulphur, chlorine, water, and zinc, was effected. Since then so many syntheses of this kind have been achieved as to prove beyond doubt that the same chemical forces act both in the organic and inorganic worlds. The separation of the two branches, Organic and Inorganic Chemistry, from each other is, however, still retained for con- venience sake, although the original reasons for this separation, which at the time was more or less a matter of necessity, have since been found to be erroneous. In consequence of the great capacity of combining with one another which carbon atoms possess, the number of organic compounds is extraordinarily large, and in order to be in a position to study them, it is necessary to have a knowledge of the other elements, including (B480) 1 A this htetal?.: -This 'garbojx compounds, many of the most im- portant bf which ntain k only carbon and hydrogen, or carbon, hydrogen, and oxygen, also stand in a closer relationship to each other than do the compounds of the other elements. Partly upon grounds of convenience, carbon itself and some of its principal compounds, such as carbonic acid, which is so widely distributed in the mineral kingdom, are treated of under Inorganic Chemistry. The expressions "organic" and "organized" substances should not be confused; organized substances, e.g. leaves, nerves and muscles, and also the life-processes which go on in the interior of the organism, are treated of under Physiology and Physiological Chemistry. Constituents of the Carbon Compounds Many organic substances are composed of carbon and hydro- gen only, and are then termed hydrocarbons, for instance, ethylene, benzene, petroleum, naphthalene, and oil of turpen- tine; a vast number consist of carbon, hydrogen, and oxygen, for instance, wood spirit, alcohol, glycerine, aldehyde, oil of bitter almonds, formic acid, acetic acid, stearic acid, tartaric acid, benzoic acid, carbolic acid, tannic acid, and alizarin; many compounds contain carbon, hydrogen, and nitrogen, for instance, prussic acid, aniline, and coniine; as examples of compounds containing carbon, hydrogen, nitrogen, and oxygen, may be taken urea, uric acid, indigo, morphine, and quinine. In addition to these, sulphur, chlorine, bromine, iodine, phosphorus, and, generally speaking, the larger number of the more important elements, are also frequent constituents of the carbon compounds. Qualitative Analysis of Organic Compounds The presence of Carbon in a compound is often proved by the "carbonization" of the latter, e.g. starch, sugar, &c., when heated in a glass tube, or when warmed with concentrated sulphuric acid. Carbon compounds which readily volatilize, e.g. alcohol, chloroform, acetic acid, do not give these tests, but many of them deposit carbon when their vapours are led through a red-hot tube. The best proof of the presence of carbon is obtained by completely oxidizing the organic com- pound by either heating it with copper oxide (see below), or QUALITATIVE ANALYSIS 3 by leading its vapour over the glowing oxide. The carbon present is thus converted into carbon dioxide, and the Hydro- gen into water. Nitrogen in organic compounds is recognized (a) Frequently by a smell resembling that of burnt hair, upon heating; (b) Frequently by the presence of red fumes, or by explosion, upon heating (nitro- and diazo-compounds); (c) In many cases by the liberation of ammonia upon heating with soda-lime (Wohler)-, (d) In all cases by heating with potassium (and in most cases with sodium), and testing the metallic cyanide formed (see Cyanogen Compounds) by dissolving the fused mass in water, adding a few drops of ferrous sulphate solution, boiling, and acidifying with hydrochloric acid (formation of Prussian Blue) ; or by converting the cyanide into thiocyanate, and proving the presence of the latter by means of the blood- red coloration with ferric chloride. [See tests for hydrocyanic acid (Lassaigne).] If sulphur be likewise present, iron filings must be added. Testing for the Halogens. Direct precipitation by nitrate of silver is usually not practicable; thus, no chlorine can bo detected in chloroform even upon boiling it with AgN0 3 . The halogens are therefore tested for: (a) By heating the substance on a platinum wire with cupric oxide in the Bunsen flame, or by causing the vapour of the compound to pass over glowing copper gauze; in this way chlorine gives first a blue and then a green flame coloration, and iodine a green (Beilsteiri) ; (b) By heating the substance strongly with pure lime, and testing the solution of the naloid calcium salt produced with silver nitrate; (c) By heating in a sealed tube with fuming nitric acid and nitrate of silver, when the haloid silver salt is produced (Carius). Testing for Sulphur: (a) In many cases, upon boiling with an alkaline solution of lead oxide, brown sulphide of lead is formed (e.g. white of e gg); (b) By heating with sodium, and testing the resulting sodium sulphide with water upon a silver coin (black stain); or by means of sodium nitroprusside solution (purple-violet colora- tion) (Schonri); 4 INTRODUCTION (c) By complete oxidation in the dry way, by fusing with potassium carbonate and nitre, or by heating with mercuric oxide and sodium carbonate; or in the wet way, by fuming nitric acid (Carius), and testing the sulphuric acid produced, by barium chloride solution. In like manner Phosphorus is converted by complete oxida- tion into phosphoric acid; or, upon heating with powdered magnesia, and moistening the resulting mass with water, the presence of phosphuretted hydrogen can be recognized (Schonn). All the other Elements are tested for, after complete oxida- tion of the compound (preferably by Carius' method), in the usual way. Another method (B. 1904, 37, 2155) is to heat a small amount of the substance with sodium peroxide and twenty- five times its weight of naphthalene or cinnamic acid in an iron tube, and then test for haloids, sulphates, phosphates, &c. Quantitative Organic or Elementary Analysis Estimation of Carbon and Hydrogen (Combustion). The substance is oxidized by heating it to redness with cupric oxide (Liebig), or with other substances which readily give up oxygen, such as lead chromate, platinum and oxygen (Denn- stedt)* &c., in a tube of difficultly fusible glass, which is open either at one or at both ends. The carbon dioxide, thus produced by the oxidation of the carbon, is absorbed by a concentrated solution of caustic pot- ash contained in specially shaped bulbs,* and the water, pro- duced by the oxidation of the hydrogen, in a U-shaped calcic chloride tube, both tubes being weighed before and after the combustion. If the substance (0'2 to 0*3 grm.) is solid, it is either mixed with fine, dry copper oxide (Liebig, Jlunsen), or placed in a porcelain or platinum boat and burnt in a stream of air or oxygen (open tube). Liquids are weighed out in small tubes or thin sealed glass bulbs. When nitrogen is present, a coil of tightly -rolled copper-wire gauze is placed in the front part of the combustion tube and heated to red- ness, in order to reduce any oxides of nitrogen which may be formed in the subsequent combustion. In the presence of sulphur or of the halogens, lead chromate, which has been * For details see Sudborough and James' Practical Organic Chemistry, Chap. V, B. QUANTITATIVE ANALYSIS 6 fused and then powdered, is used instead of copper oxide, so as to convert any Cl, S0 2 , &c., into PbCl 2 , PbS0 4 , &c., and thus prevent them from passing into the potash solution. When only halogens, without sulphur, are present, the combustion is carried out with copper oxide, a copper, or still better a silver spiral, which is kept cool, being placed in the fore-part of the tube to retain the halogens. In the presence of alkalis or alkaline earths (which would retain carbon dioxide), lead chromate mixed with -^ of its weight of potassic bichromate is used; the chromic acid then expels all the carbonic acid. Explosive compounds must be burnt in a vacuum. From the weights of carbon dioxide and water found, the percentages of C and H are readily calculated: C = AC0 2 ; H = i Hs(X Estimation of Nitrogen. This estimation is either relative or absolute. In the former case the proportion between the nitrogen and the carbon dioxide evolved is determined (LieUg, Bunsen); in the latter the nitrogen is either estimated as such volumetrically, or as ammonia. The conversion into Ammonia is effected by heating the substance strongly with soda-lime (Will, Farrentrapp), or by creating it with strong sulphuric acid and permanganate of potash (Kjeldahlj Z. Anal. Ch. 22, 366; also B. 19, Kef. 852; 24, 3241; 27, 1633). The ammonia is then either titrated directly by absorption in standard acid, or transformed into ammonium platinichloride, (NH 4 ) 2 PtCl 6 , which is weighed, or else ignited, and the weight of the residual metallic pla- tinum noted. In the Gasometric Estimation of Nitrogen the substance is mixed with copper oxide, a copper spiral being also used in the front part of the tube, and the combustion is carried out in the usual way, but in a stream of carbon dioxide; the C0 2 is either generated from magnesite in the tube itself, or led through it. The nitrogen is collected over mercury and aqueous caustic potash (Dumas), or directly over potash (ZulkowsJcy, Schwarz, Scliiff, &c.), in some special form of nitrometer. Its percentage is obtained by reducing the volume to the volume at normal temperature and pressure, determining the -weight of this volume of nitrogen from the fact that 1 c.c. of 6 INTRODUCTION dry nitrogen at and 760 mm. weighs 1*2489 mg., and ex- pressing the result in percentage. The Gasometric method may be used for all classes of nitrogen compounds, but the Soda-lime method cannot be used for nitro compounds, certain bases, and various other groups of compounds, as the nitrogen of these is not completely transformed into ammonia upon heating with soda-lime. For the simultaneous determination of carbon, hydrogen, and nitrogen the combustion must be carried on in a stream of pure oxygen, the mixture of gases escaping from the potash bulbs being collected over a solution of chromous chloride, which absorbs the oxygen, but not the nitrogen (A. 1886, 233, 375). Estimation of Sulphur and Phosphorus. The Sulphur is estimated as sulphuric acid, being converted into this (a) In the wet way, by heating the substance with fuming nitric acid at 150-300 in a sealed tube (Carius), or in a com- bustion-tube in a mixed stream of nitric oxide and oxygen (Claessori), or nitric acid vapour (Klasori). (b) In the dry way (and this method is only available in the case of the less volatile compounds) by fusing the sub- stance with potassic hydroxide and nitre, or with soda and chlorate or chromate of potash, also by heating with soda and mercuric oxide, or with lime in a stream of oxygen. Phosphorus is estimated by analogous methods. Estimation of the Halogens. Here also the organic sub- stance is completely decomposed (a) After Carius, as above, in a sealed tube, with fuming nitric acid and solid silver nitrate, by which means the halogen is converted into its silver salt; (b) By heating the compound strongly with pure lime in a hard glass tube, or in two crucibles, one of which is inverted in the other, or with sodic carbonate and nitre in a tube. The chloride formed is precipitated with silver nitrate in the usual way; (c) By the action of nascent hydrogen (sodium and alcohol), the halogen in the organic substance can frequently be con- verted into its hydrogen compound (Stepanow). Dennstedt, B. 1897, 30, 1590, 2861, has described methods for estimating C, H, Cl, and S in one operation. Metallic and acidic radicals, contained in organic salts, can often be estimated directly by the usual methods. Oxygen is almost invariably determined by difference j direct DETERMINATION OF MOLECULAR WEIGHT 7 methods of estimation have been proposed by Baumhauer, Laden- burg, Stromeyer, and others. The carbon estimation is usually too low (0"05 O'l), owing to leakage and incomplete absorption, that of hydrogen too high (0-1 0'2), owing to the difficulty of completely drying the cupric oxide. Nitrogen estimations are also usually too high, owing to the difficulty of completely freeing the carbon dioxide from air. The Calculation of the Empirical Formula The same principle applies here as in the case of inorganic compounds, i.e. the percentage numbers found are divided by the atomic weights of the respective elements, the relative pro- portions of the quotients obtained being expressed in whole numbers. For instance, acetic acid being found to contain 40-11 p.c. carbon, 6 '80 p.c. hydrogen, and, consequently, 53*09 p.c. oxygen, the quotients are to each other as 3-34 : 6 -80 : 3 -32 = 1:2:1. The simplest analysis-formula of acetic acid would therefore be CH 2 0. Sometimes figures are obtained which correspond with equal nearness to different formulae, between which it is therefore impossible, without further data, to choose. For instance, a sample of naphthalene yields on analysis 93-70 p.c. carbon and 6 '30 p.c. hydrogen; the quotient pro- portion here is 7 -81 to 6'30 = 1-239:1, which corresponds equally well with the numbers 5:4 or 11:9. The formula C 5 H 4 requires 93'75 p.c. carbon and 6-25 p.c. hydrogen, and the formula C n H 9 , 93-62 p.c. carbon and 6*38 p.c. hydrogen, the deviations from the actual numbers found being in both cases within the limits of experimental error. Therefore other considerations must be taken into account here, in order to decide between the two formulae. The formula derived from the results of analyses is termed the Empirical Formula, and expresses the simplest numerical relationship between the atoms of the elements present. The actual molecular formula may be a multiple of this, and has to be determined according to special principles. Determination of Molecular Weight 1. BY CHEMICAL METHODS. Our chemical formulae (e.g. CH 2 0) express not merely a 8 INTRODUCTION percentage relation, but at the same time the smallest quantity of the compound which is capable of existing as such, i.e. a molecule of it. This molecule is ideally no longer divisible ' * mechanical means, but only by chemical, and then into its J stituent atoms. If the formula CH 2 were the correct on/f( acetic acid, then the amount of oxygen (or carbon) contained ii a molecule would be indivisible, and that of hydrogen divrsibl only by 2. Since, however, it has been observed that ; on< fourth of the total hydrogen in acetic acid is replaceable, e.l by a metal, with the formation of a salt, it is obvious that ' ' quantity of hydrogen in the molecule must be divisible and so the formula must contain at least 4 atoms of hydro^ and must therefore be C 2 H 4 2 , or some multiple of it. 1 is, in fact, the case. Acetate of silver contains 64 '67 p.c. sil 1 and therefore 35*33 p.c. of the acetate radical; or, to 1 aton silver =108 parts by weight, there are 59 parts by weigh] the acid radical. This 59, together with 1 atom of hydro! = 1, makes the molecular weight of acetic acid 60, = 2 x = 2 x CH 2 0, = C 2 H 4 2 . This is a determination of molecular weight by chemi means. Such determinations are carried out in the easel acids generally by means of their silver salts; these are iisi normal salts, are easy to purify, are almost always from water of crystallization, and are readily analysed, is, however, absolutely necessary to know whether the is mono- or polybasic. In the case of a di-, tri-, &c., basic the above calculation must be made with reference to 2, &c., atoms of silver, whereas acetic acid being monobasic! contains only one replaceable atom of hydrogen, which \ therefore exchanged for one atom of silver. Consequent^, its formula cannot be a multiple of C 2 H 4 2 . In the determination of the molecular weights of Bases, theii platinichlorides are similarly made use of, these being almost always constituted on the type of ammonium platinichloride : (NH 3 ) 2 H 2 PtCl 6 : i.e. they contain two molecules of a mono- acid base such as ammonia combined with one atom of platinum. To determine the molecular weights of Neutral Compounds, derivatives must be prepared and examined for the proportion of the total hydrogen which is replaceable, e.g., by chlorine. For example, by the action of chlorine upon naphthalene, there is first formed the substance monochloronaphthalene, which contains 73'8 per cent 0, 4 -3 per cent H, and 21-9 per DETERMINATION OF MOLECULAR WEIGHT 9 cent Cl, these numbers giving the formula C 10 H r Cl. In the same way benzene yields the compound C 6 HcCl. In both these cases the halogen ajts by replacing hyarogen, and at least one atom of the latte in the molecule must be replaced, since fractions of an atom are necessarily out of the question. If, then, the compound oltained has the formula C 10 H 7 C1, it follows that |^th of the H present has been replaced by Cl, and there must consequently be 8, 8 X 2, or 8 X 3, &c., atoms of hydrogen in the compound, and likewise 10 atoms, or some multiple of 10, of carbon. But a multiple of 8 or 10 may be rejected, since no compounds have been observed which would indicate the replacement of T Vth of the total hydrogen. This leads to the formula C 10 H 3 for naphthalene, the other possible formula got by analysis viz. C n H 9 (see p. 7), being now untenable. In a similar way the formula of benzene is found to be C 6 H 6 . 2. BY PHYSICAL METHODS. (a) By Estimating the Fapour Density. According to the law of Avogadro (1811) and Ampere (1814), all gases under similar conditions, i.e. in the perfectly gaseous state and under the same temperature and pressure, contain in equal volumes equal numbers of molecules. It follows from this that the weights of equal volumes of different gases are proportional to the weights of equal numbers of their con- stituent molecules, in other words, the molecular weight is proportional to the specific gravity of the gas. Thus, if M x be the molecular weight of any given substance required, M that of oxygen, S the vapour density or specific gravity of the former as compared with oxygen taken as 16*, M X :M = S:16. And since M = 32, M x = S X 2. To determine, therefore, the molecular weight of a gas or vapour, one has only to find its density, and to multiply this by 2. To take an example, the specific gravity of acetic acid vapour being found to be 30, then M = 60, and the mole- cular formula is C 2 H 4 2 = 60. * Oxygen is taken as standard (0 = 16) for vapour density, since it is now customary to take it as standard in atomie-weight determinations. For all practical purposes, one may take the density compared with hydrogen as unity. 16 INTRODUCTION It is essential to the application of this method that the temperature of the vapour shall be so high above the boiling- point of the substance that the latter is in the perfectly gaseous state, remaining at the same time undecomposed. The only common method employed in the chemical labora- tory for vapour-density determinations is that due to Victor and Carl Meyer. In this process the small tube containing the substance is dropped into a vertical glass tube, the lower and wider part of which is cylindrically shaped and sealed. This is kept warm at a constant temperature, being surrounded by a long glass mantle in which a suitable liquid boils, the upper part of the mantle itself serving for the condensation of the vapour. The displaced air alone escapes, and is collected over water and measured. No determination, therefore, of the temperature of the vapour of the substance in question is required. Only about Ol grm. substance is required. In all cases the vapour density is the weight of the vapour, divided by the weight of an equal volume of hydrogen (see note, p. 9), which can readily be calculated in the usual manner. If, instead of having the apparatus filled with air, hydrogen is employed, the greater molecular velocity of the latter allows of the conversion of substances into vapour at 30-40 below their ordinary boiling temperatures (V. Meyer and De- muth, B. 1890, 23, 311). Until a few years ago, the determination of molecular weights by physical means was restricted to the different modifications of the method which has just been described, and consequently it could only be carried out with substances which were either already gaseous, or which could be rendered so without decom- position. The recent important researches of van't Hoff, Eaoult, Ar- rhenius, Ostwald, and others, upon the nature of solution in particular, the proof that the laws of Boyle, Gay-Lussac, and Avogadro are applicable to solutions as well as to gases now permit, however, of the ready determination of the molecular weights of substances in solution, and therefore of compounds which could not be volatilized without decomposition. This is accom- plished as follows : (b) By Measuring the Depression of the Freezing Tempera- ture of Solutions, or Cryoscopic Method. This method is based upon the following data : Each solvont has a perfectly definite freezing-point (e.g. water 0, benzene, DETERMINATION OF MOLECULAR WEIGHT 11 5'0, and glacial acetic acid, 16-75), but the introduction of a solute into such a solvent lowers the freezing-point, and within certain limits the lowering is directly proportional to the con- centration of the solute. Raoult has shown that gram mole- cules of different substances dissolved in equal weights of the same solvent lower the freezing-point of the solvent to. the same extent, or " equimolecular solutions have the same freezing-point ". The molecular lowering of the freezing-point is the lowering which would be produced when ,the gram molecule (M) of the substance was dissolved in 100 grams of solvent, and is usually denoted by C. This varies for different solvents, and may be determined experimentally by using substances of known molecular weight, e.g., p grams of a sub- stance of molecular weight M dissolved in 100 grams of solvent caused a depression of A in the freezing-point of the solvent. 'A = depression for p grams in 100 grams of solvent M 100 . C = M|- The value C may also be calculated theoretically from van't 2T 2 Hoffs equation C = , where T =. absolute freezing- 100 L point of the solvent, and L is the latent heat of fusion of the solvent. Having determined the value C (for water C = 18-5, for glacial acetic acid 39, and for benzene 50), we may use the same equation C = M- or M = 9? p A for calculating M when A = lowering of the freezing-point produced by dissolving p grams of a substance of unknown molecular weight M in 100 grams of solvent. It is obvious that this method cannot be employed with satisfactory results for determining the molecular weights of electrolytes in ionizing media. It has also been found that certain hydroxylic substances give abnormal values in benzene solution, owing to the fact that benzene tends to cause the association of molecules of such compounds. Ebulliscopic Method. Molecular weights may also be determined by the raising of the boiling-point of a suitable 12 INTRODUCTION solvent produced by the introduction of known weights of the substance into a given weight (or volume) of the solvent. The principles involved are exactly the same as those dis- cussed above in the cryoscopic method, but the forms of apparatus are different. (J. C. S. 1898, 73, 502.) Descriptions of apparatus employed in these physical methods are given in Sudborough and James' Practical Or- ganic Chemistry, Chap. VIII. (c) By Measurement of the Osmotic Pressure. According to van't Hoff (Z. phys. Chem. I. 481), equimole- cular solutions exert the same osmotic pressure, or are isotonic, equality of temperature being assumed. From this it follows, by reasoning analogous to that in section (&), that the mole cular weight of a compound can be ascertained by measuring the osmotic pressure of its solution. The method is rarely used in chemical laboratories. (Ladenburg, B. 1889, 22, 1225; M. Planck, Z. phys. Chem., 1890, 6, 187.) (d) By Measurement of the Lowering of the Vapour Pressure. According to Eaoult, the same generalizations hold for the lowering of the vapour pressure of a solvent by the introduc- tion of a solute, as for the lowering of the freezing-points or the raising of the boiling-point. Three methods of applying the principle for the determination of molecular weights have been described. This law can be deduced theoretically from the preceding one (c), and it also stands in theoretical continuity with that of (b). (See Will & Bredig, B. 1889, 22, 1084; Barger, J. C. S. 1904, 85, 206; Perman, ibid. 1905, 87, 194; Blacbnan, ibid. 1474.) (e) By Measuring the Decrease in Solubility. (Nernst, B. 23, Eef. 619. See also Ostwald-Luther.) Polymerism and Isomerism The determination of molecular weight is of the first im- portance, because different substances very frequently have the same percentage composition and therefore the same empirical formula, and yet are totally distinct from one another. This difference is often due to differences in the complexities of the molecules. Thus formic aldehyde, CH 0; acetic acid, C 2 H 4 2 ; lactic acid, C 3 H 6 3 ; and grape-sugar, C 6 H 12 G , have all the same percentage composition; as have also ethylene, C 2 H 4 ; THEORY OF VALENCY 13 propylene, C 3 H 6 ; and butylene, C 4 H 8 . Compounds standing in such relation to each other are termed polymers. Very frequently, however, substances which are totally distinct from each other possess both the same percentage composition and the same molecular weight; that is to say, these com- pounds are made up not only of the same elements, but also of an equal number of atoms of these elements; such sub- stances are termed isomers or metamers. (See Ethers.) Thus, for instance, common alcohol and methyl ether, the latter of which is obtained by heating methyl alcohol with sul- phuric acid, have one and the same molecular formula, C 2 H 6 0. The striking phenomenon of isomerism is most readily ex- plicable on the assumption that for the molecule of each com- pound there is a definite arrangement of the atoms, and that this arrangement or grouping is different in the molecules of the two isomerides. This difference in grouping may be con- sidered as being due to a difference in the linking powers of the atoms, as is indicated by the dissimilar chemical behaviour of isomers, and explained by the theory of valency. Chemical Theories; the Theory of Valency After the fall of the Electro - Chemical theory, unitary formulae in contradistinction to the earlier dualistic formulae were much used; thus alcohol had the formula C 4 H 6 2 (using the old equivalent weights). The necessity for com- paring substances of complicated composition with simpler ones, taken as " Types ", had already repeatedly led to the propounding of new theories for representing the constitution of organic compounds, e.g. the older Type theory (Dumas), and the Nucleus theory (Laurent). These obtained a firmer basis through Gerhardfs Theory of Types, which received support more especially from the dis- covery of ethylamine and other ammonia bases (Wurtz, 1849, and Hofmann, 1849, 1850), the proper interpretation of the formulae of the ethers (Williamson, 1850), and the discovery of the acid anhydrides (GerharcU, 1851). All compounds, inorganic as well as organic, were in this way compared with simpler inorganic substances taken as " Types", of which Gerhardt named four, viz. \ H\ H1 SUr I ClI H/ || N 14 INTRODUCTION" The first two of these really belong to the same type. Thus the following formulae were arrived at: : g} 5) Potassium chloride Ethyl chloride Acetyl chloride )0 1)0 N H }0 Potassium hydroxide Nitric acid Alcohol Acetic acid Potassium oxide Nitric anhydride Ether Acetic anhydride C 2 H 6 ) C 2 H 3 0) H ^N H VN H J H J Ethylamine Acetamide &c. &c. Organic compounds could thus, like inorganic, be referred to inorganic types by assuming in them the presence of Radicals (e.g. ethyl, C 2 H 5 ; acetyl, C 2 H 3 0, &c.), i.e. of groups of atoms which play a part analogous to that of an atom of an element, and which can be transferred by double decom- position from one compound to another. Thus ethyl chloride, C 2 H 5 C1; alcohol, C 2 H 0; ethylamine, C 2 H 7 N; ether, C 4 H 10 0; &c., were represented as containing the same radical C 2 H 5 , ethyl, and the close relationship existing between these com- pounds now found expression in the type formulae. Sulphuric acid, H 2 S0 4 , was derived from the double water- type, thus and chloroform, CHC1 3 , and glycerin, C 3 H 8 3 , from the triple hydrochloric acid and water types the assumption being made that the radicals (C 2 H 5 )', (S0 2 )", (CH)"', and (C 3 H 5 )"' could replace a number of hydrogen atoms corresponding with the number of accents (') marked upon them, %,e. that they were monatomic, diatomic, &c. To the above THEORY OF VALENCY 16 three types KekuU afterwards added a fourth, of especial im- portance as regards the carbon compounds, viz. It was then found that many compounds could be referred equally well to one or another of these types, methylamine, for instance, either to CH 4 or to NHg, thus CH,} or H IN. The assumption, already mentioned, of the atomic groups (radicals) which in these types replaced hydrogen, led further to more exact investigations of the chemical value, i.e. the replaceable value, of those groups as compared with that of hydrogen. In this way chemists Learnt to distinguish between mono-, di-, tri-, &c., valent groups, and, generally speaking, to pay more attention to equivalent proportions. As the outcome of his researches upon organo-metallic com- pounds, Frankland formulated in 1852 (A. 85, 368) the law that the elements nitrogen, phosphorus, arsenic, and antimony tend to form compounds which contain three or five equivalents of other elements. KekuU then, in 1857-58 (A. 104, 129; 106, 129), proceeded to show that a more profound idea (the " Type idea ") lay at the root of the types themselves, viz., that there are mono-, di-, tri-, and tetra valent, &c., elements, which possess a corre- sponding replacing or combining value as regards hydrogen; and that hydrogen is therefore monovalent, oxygen divalent, nitrogen trivalent, carbon tetravalent, and so on. With the introduction of the CH 4 type by Kekuli, and the establishment of the tetravalent nature of the carbon atom accompanying this, were connected the endeavours of Kolbe to derive the constitution of organic compounds from carbonic acid (according to Kolbe C 2 4 , C = 6, = 8), by the ex- change of oxygen for organic radicals (A. 113, 293); see also, for further details, Kopp's " Entwickelung der Chemie in der neueren Zeit" (Oldenbourg, Munich, 1873), and E. V. Meyer's 16 INTRODUCTION " History of Chemistry " (Macmillan, 1891), Schorlemmer's "Rise and Development of Organic Chemistry " (Macmillan). The question of the valency of elements, a point which it Is often difficult to decide in inorganic chemistry, is infinitely easier of determination in the case of the carbon compounds, because the carbon atom is tetravalent towards hydrogen as well as towards chlorine and oxygen. Since the atom of hydrogen, as the unit of valency, is monovalent, and, further, since the divalence of the oxygen atom cannot reasonably be doubted, the valency of the three " organic " elements hydrogen, oxygen, and carbon may be considered as resting upon a sure basis, as may also the conclusions drawn therefrom, and this all the more since the most important carbon compounds are made up of those three elements. Within the past few years the divalency of the oxygen atom in many organic compounds has been brought into ques- tion. The readiness with which many oxy-derivatives form definite compounds with mineral acids and with metallic salts would appear to indicate that in many cases the oxygen atom can even be tetravalent (see Oxonium Salts). In certain com- pounds it has also been suggested that the carbon atom may be trivalent (see Triphenylmethyl). Explanation of Isomerism; Determination of the Constitution of Organic Compounds The phenomenon known as isomerism is elucidated to a great extent by the theory of valency. If two substances have the same molecular formula, i.e. both contain the same elements and the same number of atoms of the respective elements in their molecules, then the obvious conclusion to be drawn is that in the two molecules the atoms are differently arranged. The methods adopted in determining the manner in which the atoms are linked together, or, as it is called, the determination of the chemical constitution of the compound, is usually based on the following points: (a) The respective valencies of the atoms constituting the molecule. A compound C 9 EL must have the structural formula H-)CC^-H, or, as H/ X H it is often more shortly written, CH 3 CH 3 , if each atom of carbon is to be represented as tetravalent, and each hydrogen atom as monovalent. Similarly the compound CH 4 must be DETERMINATION OF CONSTITUTION 17 TT TT represented as TTX^XO _ H' or ^ 3 ' ^"^ ^ ^ e car ^ on atom j^ tetravalent, the oxygen atom divalent, and the hydrogen atoms monovalent. (b) A study of the more important methods of formation and of the chemical reactions in which the com- pound in question can take part. To select as an example ethyl alcohol, C 2 H 6 0. We can start from ethane, CH 3 CH 3 , and by the action of chlorine replace one of the hydrogen atoms by a chlorine atom, and thus obtain the compound CH 3 .CH 2 C1. When this is boiled with dilute alkalis (KOH), it gives potassic chloride and ethyl alcohol, C 2 H 5 C1 + KOH = C 2 H 6 -f KC1. From this it is obvious that the monovalent chlorine atom becomes replaced by an atom of oxygen and an atom of hydrogen. This can be readily understood if we assume that these two atoms enter in the form of the monovalent hydroxyl group, O H, and the constitutional Hv /H formula for ethyl alcohol would then be H-^C C^-H W X) H CH 3 CH 2 OH. This formula is further supported by a study of most of the chemical reactions in which ethyl alcohol can take part. It can react with metallic sodium, yielding a com- pound, sodic ethoxide, C 2 H 5 NaO; however much sodium is employed, only one of the six hydrogen atoms present in the alcohol molecule can be replaced by sodium, and this atom is presumably the one differently situated from the remaining five, namely, the one attached to oxygen. The presence of the hydroxyl, H, group is further confirmed by the action of hydric chloride or of phosphorus trichloride on the alcohol, when an atom of chlorine takes the place of the OH group. or and 3CH 3 .CH 2 .OH + PC1 3 = 3CH 3 .CH 2 C1 + P(OH) 3 . Isomeric with ethyl alcohol is the substance known as dimethyl ether. Although it has the same molecular formula, it differs altogether from ethyl alcohol in its chemical and physical properties. The only other possible method of link- ing up the atoms 2C, 6H, and 0, is H^C O C^H, in which the two carbon atoms are not directly united to one another, and in which the six hydrogen atoms are all similarly (B480) B 18 INTRODUCTION situated. The chemical reactions of dimethyl ether are in per- fect harmony with this constitutional formula. It does not react with metallic sodium, and hence presumably does not contain an OH group. When acted upon by hydriodic acid, under suitable conditions, the molecule is ruptured, as repre sented by the following equation: CH a .O.CH 3 -f HI = CH 3 I + CH 3 .OH. Similarly, whenever the oxygen atom is removed a rupture of the molecule occurs, and the two carbon atoms in the mole- cule become separated. The constitutional formula for acetic acid is written H \ O H-pC C^Q TT- This formula corresponds perfectly with the chemical behaviour of acetic acid and explains the fol- lowing facts: (a) that one of the hydrogen atoms of the acid possesses properties different from those of the three others, the first-named being easily replaceable by metallic radicals; (b) that the two oxygen atoms behave differently, not being equally readily exchangeable for other radicals; (c) that dif- ferent functions appertain to the two carbon atoms, so that one of them being already joined to two atoms of oxygen easily gives rise to carbonic acid, while the other connected as it is with three atoms of hydrogen readily passes into methane or methyl compounds. On account of the innumerable cases of isomerism which have been observed, simple molecular formulae alone are in most cases insufficient for the discrimination of organic com- pounds; it generally requires the constitutional formulae to give a clear idea of their behaviour and of their relations to other substances. Careful study has made it possible within the last few decades to find out the mode in which the atoms are combined in the molecules of most organic compounds, and from this to deduce new methods for their preparation. The constitutional formulas thus arrived at are sometimes very simple, sometimes, however, very complicated, as, for instance, in the cases of citric acid and grape-sugar (which see). NATURE OF CARBON ATOM 19 Rational Formulae Great latitude is permissible as regards the mode of writin* constitutional formulae, according to the particular points which it is desired to emphasize. A formula on paper is not as a rule intended to represent the symmetrical or spatial arrangement of the atoms in a compound. A shortened constitutional formula, which indicates more chemical relations than an empirical one does, is called a rational formula; e.g. C 2 H 5 OH, alcohol; (CH 3 ) O, methyl ether. For acetic acid, instead of the constitutional formula already given on page 18, the following rational formulas may be used: CH 3 -C<OH, CH 3 -CO.OH, CH 3 -C0 2 H, CH 3 .C0 2 H, (CH 3 .CO)OH, C S H 3 O.OH, H^A); and so on. The Nature of the Carbon Atom The theoretical views and the knowledge thereby gained of the nature of the carbon atom may be expressed somewhat as follows : 1. The carbon atom is tetravalent. 2. Its four valencies are all equal; a mono-substituted deri- ative of methane exists in only one form, that is, isomerism is ot met with. 3. The atoms or atomic groups which are held bound by hese four valencies cannot readily exchange places with each ther (the Le Bel-van 't Ho/ law, 1874). Proof: there are in early every case two physically different tetra-substitution roducts, C, a, b, c, d of methane (see Stereochemistry). 4. Several carbon atoms can be connected together by either ne, two, or three valencies (see p. 23): CC, C:C, C:C. 5. Similarly, three or more carbon atoms may be united, rming in this way the so-called "carbon chains" (see p. 32), nus The number of the atoms so linked together may be very irge, in some cases probably several hundreds. 6. These carbon atoms form either open or ring-shaped losed chains. 20 INTRODUCTION Open chains are those which have separate constituent atoms at either end, as in (5). In closed chains or rings, on the con- trary, the first and last constituent atoms are linked together (although there may at the same time be subsidiary branches from them), thus A /x /V A i, ^ A A. \- c-c-c. 7. The atoms of other elements, with the exception, of course, of monovalent ones, may likewise take part in the formation of such chains, both open and closed; for example: C Cv C Cv sC (X c <y c c/ \c-cx The above figures (the hexagon, &c.), which are made use of to represent such chains or rings, are merely meant to be pictorial (schematised) and not geometrical; the question of the spatial arrangement of atoms in compounds will be dealt with later. Homology In the study of carbon compounds it is customary to grou together all the compounds with similar chemical structur and similar chemical properties, and to arrange the member of such a group, or homologous series as it is termed, accordin to the order of their molecular complexity, i.e. according t the number of carbon atoms contained in the molecule. For example: Paraffins. Fatty acids. methane ...... CH 2 O 2 formic ethane ...... C 2 H 4 O 2 acetic propane ...... C 3 H 6 O 2 propionic o butane ...... C 4 H 8 2 butyric &c. It is found that in any such homologous series a number c generalizations can be drawn. Some of the more important c these are : 1. For each homologous series we can write a general f& HOMOLOGOUS SERIES 21 mula which will represent the composition of all the members of the series; for example, the general formula for the paraffins is C n H 3n+2 , and for the saturated fatty acids Cyi.^^ 2. If any particular member in a series is selected, it is found to differ in composition from the member immediately preceding, and also from the one immediately succeeding, it by a definite amount, namely, CH 2 . Or, expressed in other words, any member of the series may be regarded as derived from the member immediately preceding it by the introduction of a methyl group, CH 3 , for an atom of hydrogen. It follows, therefore, that all the members of the paraffin series may be regarded as derived from GEL by the addition of a given number of CH 2 groups, and the general formula is for this series CH 4 -f- CH 2 , or more simply 0^3^+ a- 3. The chemical properties of the different members of the series vary but slightly, so that a description of the chemical properties of any one member may be taken, as a rule, to apply to the other members. 4. In studying the physical properties, well-marked grada- tions are observed as the number of carbon atoms increases. In the case of liquids, the boiling-point is found to rise as the complexity of the molecule increases. In certain series, e.g. the paraffins, the first few members are gases, then follow liquids with gradually increasing boiling-points, and ultimately solids with extremely high boiling-points. Other physical data, such as melting-point, specific gravity, solubility, &c., are affected in very much the same manner. In the paraffin series the grouping together of the carbon atoms must be conditioned by themselves, since hydrogen, as a monovalent element, cannot be the cause of it. In all^the higher hydrocarbons the carbon atoms are therefore combined together in the form of a chain, as shown in the following graphical representations : C C C, C, C'C-C'C, or C'C; and so on. C C C in C 2 H 6 in C 3 H 8 in C 4 H 10 Various cases can occur in the mode of combination of the carbon atoms (Isomers). (See Hydrocarbons of the Methane Series.) Law Q f Even Numbers of Atoms. The u^ ber of hydrogen 22 INTRODUCTION atoms in the above hydrocarbons is always divisible by two. Should they therefore be partially replaced by other elements, the sum of these latter, if their valencies are expressed by odd numbers, e.g. Cl, N, and P, and of the remaining hydrogen atoms taken together must, as a necessary consequence of the law of equivalent proportions, remain an even number. Radicals According to LieUg, radicals were groups of atoms capable of a separate existence, which played the parts of elements, and, like these latter, could combine among themselves and be exchanged from one compound to -another. Later on, the postulate that such radicals must also be capable of existing in the free state was allowed to lapse, and they were frequently defined shortly as "the residues left un- attacked by certain decompositions ". Now, however, it is usual to designate as radicals only those atomic groups which are found repeating themselves in a comparatively large number of compounds derived from one another, and which play in these compounds the part of a simple element, e.g. CH 3 , methyl; C 2 H 3 0, acetyl; by this defi- nition the question of their existence or non-existence in the free state does not arise. The radical methyl, for example, is not known in the free state, since, when its formation might be expected, ethane (dimethyl), CH 3 CH 3 , is obtained instead (see p. 37). Such radicals may be mono-, di-, or tri- valent, &c., according to the number of monovalent atoms which they are capable either of replacing or of combining with, so as to form a saturated compound; for instance, (CoH 4 )", ethylene, is divalent; (CgHg)'", glyceryl, trivalent; (CH)'", methine or methenyl, likewise trivalent, &c. The monovalent residues, C n H 2n+1 (methyl, ethyl, &c.), which form the radicals of the monovalent alcohols, CJEt^OH, are frequently termed alJcyls, or alphyls, while the divalent residues, CaHay are known as alkylenes. At the present time it is also customary to speak of single atoms as radicals; e.g. we have the chloride or iodide radical, and further, the hydric radical which is characteristic of acids. CLASSIFICATION 23 Classification of the Hydrocarbons, &c. The hydrocarbons which have already been described are termed "saturated" compounds, since they cannot take up more hydrogen. But besides these there are hydrocarbons, &c., poorer in hydrogen, or " unsaturated ", such as C 2 H 4 , ethylene, and C 2 H 2 , acetylene, corresponding with which there are numerous homologous series. The constitution of these is explained, as will be seen later, by the assumption of a double or triple bond between neigh- bouring carbon atoms, for instance C 2 H 4 is written CH 2 :CH^ C a H 2 is written CH'CH. From these different hydrocarbons, as starting-points, the most various substitution products, such as alcohols, aldehydes, ke tones, acids, amines, &c., are derived by exchange of the hydrogen for halogen, oxygen, nitrogen, &c. To another class of hydrocarbons belongs that most impor- tant compound benzene, C 6 EL which contains eight atoms of hydrogen less than hexane, C 6 H 14 . With regard to its con- stitution, the theory of the existence of a closed chain of six carbon atoms has been advanced. (See Benzene Derivatives.) From benzene are derived an immense number of the most different homologous and analogous hydrocarbons and substi- tution products, alcohols, aldehydes, acids, and so on. Thus benzene, like methane, is the mother substance of numerous organic compounds. What has just been said with regard to benzene also holds good for various other compounds, which are characterized from a chemical point of view by containing a closed (ring) chain. These are : (a) Trimethylene, C 3 H 6 ; Tetramethylene, C 4 H 8 ; and Penta- methylene, C 5 H 10 . (b) Pyridine, C 5 H 5 N, a strongly basic nitrogenous compound, but one which at the same time resembles benzene closely in many respects. (c) Furane, C 4 H 4 0; Pyrrol, C 4 H 5 N; Thiophene, C 4 H 4 S; Pyrazole, C 3 H 4 N 2 ; Thiazole, C 3 H 3 NS; &c. Some of these fatter compounds are extremely like benzene, others like pyridine ; several of them are as yet only known in the form of derivatives. Like benzene, they are all mother- substances of in many cases long series of compounds. 24 INTRODUCTION Organic chemistry is therefore divided into the following sections : 1. Chemistry of the Methane Derivatives or Fatty Com- pounds, or Aliphatic Compounds (from dAoi^, fat), so called because the fats and many of their derivatives belong to this group. This section comprises all carbon compounds with open chains. A few compounds, which are really closed-chain or ring compounds, will be mentioned in this section on account of their close relationship to certain open- chain compounds; as an example, we may take succinic anhydride CH 2 .CO\ GH 2 which is formed by the elimination of water from succinic acid, OH-CO.CH 2 .CH 2 .CO.OH. 2. Cyclic or closed-cnain compounds. This section is usu- ally divided into two sub-sections. (a) Chemistry of the carbocydic compounds, which comprises the study of all compounds built up of a ring of carbon /~1TT atoms. As examples we have 2 ^>CH 2 , Trimethylene ; CH 2 ' Tetramethylene carboxylic acid; Benzene ; &c - (b) Chemistry of the heterocyclic compounds, comprising the study of all ring compounds which contain other atoms, in addition to carbon atoms, as part of the ring, e.g. CH.CH, CH.CH, OTT 8 E Furane Thiophene Pyridine Physical Properties of Organic Compounds The physical properties of organic compounds are often of the greatest importance for their characterization, and physical data are frequently made use of in determining the purity of a chemical compound. Solubility. The carbon compounds vary enormously as regards their solubility in various solvents. As a rule, a given solvent dissolves those substances which are chemically closely allied to it. As example of this, we have the fact that water tends to dissolve hydroxylic compounds, especially if SPECIFIC GRAVITY 25 there are several hydroxy groups in the molecule, e.g. mannitol, glucose, and pyrogallol. Benzene tends to dissolve most hydrocarbons, and ether dissolves the majority of simple organic compounds, with the exception of salts of acids. The usual method of determining the solubility of the given sjubstance is to prepare a saturated solution of the substance at the temperature required. This is accomplished by one of two methods : (a) Shaking the finely-divided solute for some time in contact with the solvent at the given temperature, care being "taken that there is always some undissolved solute left over. (b) If the solute is more soluble in hot than in the cold solvent, a concentrated hot solution is prepared, and is then allowed to cool down to the temperature required, care being taken to stir the solution so that the excess of solute crystallizes out and a supersaturated solution is not obtained. A known weight or volume of the clear saturated solution is taken, and the solvent removed by evaporation, and the residual solute weighed. The result is usually expressed in the form 100 grams of solvent dissolve x grams of solute at f . Specific Gravity and Specific Volume. The specific gravity of a liquid is an important criterion for the purity of the sub- stance. This is usually determined in a specific-gravity bottle, Sprengel tube, or Pyknometer. The pyknometer is filled with pure water at a given temperature (usually 4 or 15) and carefully weighed. It is then dried, filled with the liquid at a fixed temperature, and again weighed. The ratio w ' 1( ^ U1 is the specific gravity. It is usual in giving the specific gravity to denote the temperature at which the deter- mination was made, as this varies with the temperature, and also the temperature of the water, e.g. d-^- denotes the specific gravity of the liquid at 20 compared with that of water at 4. The reciprocal of the specific gravity is known as the specific volume, and the product of this and the mole- cular weight as the molecular volume. Melting-Point. Each fusible compound has a fixed definite melting-point, and this constant is often made use of in deter- mining the purity of a solid, as the introduction of even small amounts of impurities lowers the melting-point considerably. When appreciable amounts of impurities are present, the 26 INTRODUCTION melting-point is not sharp, but ranges over a number of degrees. The melting-point is best defined as the temperature at which the liquid and solid phases of the compound are in equilibrium. The most direct and most accurate method of determining the melting-point is to place a thermometer in the molten substance and allow it to partially solidify, and note the temperature at which the mercury remains constant when the mixed solid and liquid is stirred by the thermometer. As this method involves the use of a relatively large amount of the substance, the determination is usually made by intro- ducing a very small amount of the finely-divided substance into a narrow capillary tube closed at one end. This tube is then attached to a thermometer, the substance being at the same level as the middle of the bulb of the thermometer, and the two are carefully heated in a bath of sulphuric acid. Just before the melting-point is reached the flame is removed occa- sionally, so that the temperature rises very slowly, and the melting-point can be read accurately to within -5 or -25 of a degree. As a rule, a short thermometer is used, so that the whole thread of mercury is in the bath, otherwise a correction has to be made for the length of the mercury thread which is not immersed in the hot bath. Boiling - Point. The purity of a volatile substance can usually be determined by means of the boiling-point, i.e. the temperature at which the vapour pressure of the substance is equal to the atmospheric pressure. It is usually determined by placing the bulb of the thermometer in the vapour, and if a short thermometer is employed, and the whole of the mercury thread is surrounded by the vapour, no correction is required. In each case the barometric pressure should be stated, and also whether the thread of mercury was completely immersed in the vapour. Many substances which decompose when heated under atmospheric pressure, may be distilled without undergoing decomposition under reduced pressure. This is accomplished by attaching the flask, condenser, and receiver to a mercury or water pump and exhausting. When the pressure is suffi- ciently reduced the substance is distilled, care being taken that the pressure under which the distillation occurs is mea- sured by means of a manometer. As a rule, considerable difficulty in avoiding bumping is encountered in distillations under diminished pressure; this is most readily got over by placing a piece of porous material (unglazed pot) in the liquid, STEAM DISTILLATION 27 or by slowly aspirating bubbles of air through the boiling liquid. (Compare Auschutz and fieilter, Brochure. Bonn, 1895). Fractional Distillation. Two miscible liquids with widely differing boiling-points, e.g. alcohol, 78, and aniline, 185, can be separated by the process of fractional distillation, as the lower boiling liquid distils over first. In all cases an inter- mediate fraction consisting of a mixture of the substances is obtained, but, as a rule, the greater the difference between the boiling-points of the two substances the smaller is this fraction. In many cases where the boiling-points are not very far re moved, e.g. benzene, 80, and toluene, 111, the two compounds cannot be separated by a single fractionation; it is thus cus tomary to collect fractions every 5 and to subject each oi these fractions to further distillation, using the same flask for distillation, and again collecting every 5. It is then found that there is a large fraction boiling at 80-85 and consisting of nearly pure benzene, and a large fraction, 110-111, consist- ing of pure toluene, and a number of small fractions boiling at 85-90, 90-95, &c., and consisting of mixtures of benzene and toluene. The process is often quickened by using some form of fractionating column. This consists of a long tube with bulbs blown on, and serves to lengthen the neck of the flask. The Linneman tube contains small wire -gauze cups in the constricted parts, and in these drops of the higher boiling liquid collect, and thus all the vapour has to pass through or be washed by these drops. The same purpose is served in the Glynsky tube by placing a glass ball in each constriction. (See S. Young, "Fractional Distillation". London, 1903.) It is not always possible to separate liquids by fractional distillation, for example, when the boiling-points are very close, or when the two substances form a mixture of definite boiling-point. When dilute nitric acid is distilled, water first passes over, and then a mixture of water and nitric acid, until the residue in the flask is 68 per cent nitric acid, and then it boils constantly at 126, since the vapour and the liquid in the flask have the same composition. Mixtures of constant boiling-point are always characterized by the fact that they have a vapour pressure either higher or lower than that of either of the constituents, or than that of any other mixture of the same compounds. Steam Distillation. This is the process frequently resorted to in the separation of a compound readily volatile in steam 28 INTRODUCTION from other substances, e.g. tars or inorganic salts, which are not volatile. It consists in blowing steam through the mixture, and condensing the steam and volatile compound by means of a Liebig condenser. Very often the volatile compound is prac- tically insoluble in water, and separates as an oil or solid in the distillate. The rapidity with which a given substance distils with steam depends on the vapour pressure of the sub- stance at the given temperature, and also on its molecular weight or vapour density compared with that of water. Thus a mixture of nitro-benzene and water, which may be regarded as non-miscible liquids, boils at 99; i.e. the vapour pressure of the mixture at 99 is 760 mm. The vapour pressure of water at 99 is 733 mm., and therefore the partial pressure of the nitro- 733 benzene is 27 mm. In a given volume of the mixed vapours j 27 . will consist of steam and -- of nitro-benzene, and the relative 760 weights of these volumes will be the volumes x relative den- sities, i.e. 9 * 733 : 61 * 27 i.e. 4 : 1; or, in other words, Uh 760 760 by weight of the total distillate will consist of nitro-benzene. Other methods very frequently used in the purification of solid compounds are crystallization and fractional crystalliza- tion. The method employed is essentially the same as that made use of in purifying inorganic compounds, except that organic solvents, e.g. alcohol, chloroform, benzene, carbon disul- phide, and low -boiling petroleums, are largely used. Often a mixture of two solvents is more serviceable than a single one, e.g. substances are often crystallized by solution in warm alcohol and addition of water, or solution in benzene and addi- tion of petroleum, until a slight turbidity ensues. The fact that a substance crystallizes from a given solvent in well- defined crystals does not necessarily indicate that the substance is a single chemical individual, as numerous examples of mixed crystals with definite melting-points are known, and these are not resolved when repeatedly crystallized from the same solvent. Extraction with Ether, Benzene, &c, Partition Coefficient, An organic compound can often be separated from other substances, especially inorganic salts, by shaking out with ether, separating the ethereal layer by means of a separating funnel, drying the solution with granular calcium chloride or some other suitable drying agent, and removing the ether by EXTRACTION WITH ETHER, ETC. 29 distillation. The method gives very good results when the compound to be extracted is much more soluble in ether than in water, and when the substances from which it is to be separated are insoluble in ether. When there is no marked difference in the solubilities of the given compound in ether and in water, the extraction must be repeated a number of times, in some cases even twenty, since for each compound . cone, of ethereal solution . the ratl cone, of aqueous solution ls a constant ' and ls usuall y termed the partition coefficient or coefficient of distribution of the particular substance between the two solvents. In extractions with ether it must be borne in mind that ether dissolves to an appreciable extent in water, and also water in ether.. Other liquids, such as benzene, carbon-disulphide, chloroform, &c., may be used in place of ether. When the amount of solvent to be used is limited, it is more economical to extract two or three times with small amounts of solvent rather than only once with the whole amount. As an illustration. 11 grams of a substance and 1 litre each of the non-miscible liquids, water and benzene. The solubility of the substance in benzene is ten times its solubility in water, and it has the same molecular weight in both solvents. Case /. Extracting at once with the litre of benzene, cone, of benzene solution 10 , , - j - i -. = -=-, i.e. iVth of the whole, or cone, of water solution 1 ' 1 gram, remains in the water. Case //.Extract twice with 500 c.c. of benzene. After first extraction, suppose x grams passes into the benzene, then cone, of aqueous solution is 11 x, and of the benzene 2x t = -y-, or x = 9 (approx.), and 2 grams are left .. - I I " ' in the water. After extraction with second quantity of benzene, y grams go into the benzene. Then ^ _ = y, or y 1'7 (approx.), and only 0'3 gram remains in the aqueous solu- tion. Whereas, after the single extraction with a litre of benzene 1 gram was left. For applications of this method in determining the relative strengths of acids and amines, compare Farmer and Warth (J. C. S. 1904, 1713). CLASS L ALIPHATIC OE OPEN-CHAIN COMPOUNDS I. HYDEOCAEBONS A. Saturated Hydrocarbons, cyi^ This constitutes the simplest homologous series of carbon compounds, and all the saturated open-chain compounds may be regarded as derived from these. The following list includes the more important normal hydrocarbons : Formula. Name. Melting- point. Boiling- point. Specific gravity. CH 4 C 2 H 6 Methane Ethane 186 -172 164 -84 0-415 at b.-p. 0-446 at cX Propane -37 0-536 at C 4 H 10 Butane +1 0-600 at ^6-^-12 Pentane 37 0-627 at 14 C 6 H 14 Hexane 69 0-658 at 20 C 7 H 16 Heptane 98 0-683 at 20 CoHjo Octane 125 0-702 at 20 n TT O 9 1 20 Nonane -51 150 0-718 at 20 n TT V - J '10 X - L 22 Decane 31 173 0-730 at 20 C n H24 TJndecane -26 195 0-774 at m.-p. ^12^-26 Dodecane -12 214 0-773 at ni.-p. C 14 H 30 Tetradecane +4 252 0-775 at m.-p. ^16^-34 Hexadecane 18 287 0-775 at m.-p. C 2 oH 42 Eicosane 37 205* 0-778 at m.-p. ^21-^-44 Heneicosane 40 215* 0-778 at rn.-p. ^23^48 Tricosane 48 234* 0779 at m.-p. C 31 H 64 Hentriacontane 68 302* 0-781 at m.-p. ^36-^-72 Pentatriacontane 75 331* 0-782 at m.-p. ! r< TT v ^60 rL 122 Hexacontane 101 * Under 16 mm. pressure. The first members of the series, including those with about four atoms of carbon, are gases, which gradually become more easily condensable as the number of carbon atoms in the mole- cule increases. The members which follow are liquid at the SATURATED HYDROCARBONS 31 ordinary temperature, their boiling-point rising with increasing number of carbon atoms. An increase of CH 2 in the mole- cular formula does not necessarily denote a definite increase in the boiling-point. The difference in boiling-point between hexane and heptane is 29, and between undecane and dode- cane only 19: thus with compounds of high molecular weight an increase of CH 2 does not produce so marked an effect on the boiling-point as with simpler compounds. The higher homologues, from about C 16 H 34 (melting-point 18) on, are solid at the ordinary temperature, and their melting-point gradually rises up to about 100. The highest members can be distilled under diminished pressure only. The methane homo- logues are almost or quite insoluble in water; alcohol dissolves the gaseous members to a slight extent, the liquid members easily, and the solid with gradually increasing difficulty. Their specific gravities at the melting-point increase with increasing number of carbon atoms from 0'4: up to 0*78, which is the maximum limit. This value is already almost reached by the hydrocarbon C n H 24 , so that for the higher members of the series the following law holds good: "the molecular volumes are proportional to the molecular weights " (Krafft). They are incapable of combining further with hydrogen or halogens (see p. 23), and absorb neither bromine nor sulphuric acid. They are therefore termed the Saturated Hydro- carbons. Even fuming nitric acid has little or no action upon the lower members of the series; thus, methane is not attacked by a mixture of fuming nitric and sulphuric acids, even at 150. They are also very indifferent towards chromic acid and permanganate of potash in the cold,* when oxidation does take place, they are mostly converted directly into car- bonic acid. The name of " The Paraffins " (from parum affinis), which was originally applied only to the solid hydrocarbons from lignite, has therefore been extended to the whole homo- logous series. By the action of the halogens (01, Br), substitution takes place, the substituted hydrogen combining with an amount of halogen equal to that which has entered the hydrocarbon (see Substitution products of the Hydrocarbons) : CH 3 H + C1C1 = CH,C1 + HC1. As the number of carbon atoms increases, the percentage composition of these hydrocarbons approaches a definite limit, * With the exception of compounds containing the grouping R'R"R"'CH. 32 I. HYDROCARBONS viz. that of the hydrocarbons, C n H 2n , or CH 2 , as is shown by the following table : Per cent. CH 4 C 2 H 6 C 3 H 8 C 6 H U C]cHs4 C^HIS C^H^ CssHre Limit Value, CnHfc, c H i 75-00 25-00 80-00 20-00 81-82 18-18 83-72 16-28 84-60 15-40 85-16 14-84 85-21 14-79 85-36 14-64 85-71 14-29 It is therefore impossible to distinguish by elementary analysis between two of the neighbouring higher homologues, e.g. C 22 and C 24 , C 24 and C 30 ; the only reliable data here are the methods of formation from compounds in which the number of carbon atoms in the molecule is already known, and the melting-points. homers. Only one representative each of the formula! CH 4 , C 2 H 6 , and C 3 H 8 is known, but of C 4 H 10 there are two, of C 5 H 12 three, and of C 6 H 14 already five isomers, and most of the higher hydrocarbons are known in various isomeric forms. From this the conclusion is drawn that in these different isomers the carbon atoms are differently combined, in the one case in a straight line without branching, like the links of a chain; in the other, with the formation of a branching chain. (This is of course not to be taken as meaning that they ar grouped together in space in straight lines.) Thus: or The first of these hydrocarbons, with a non-branching chain, are termed the normal hydrocarbons; the last, the iso-hydro- carbons. The principles by which such constitutional formulae are arrived at will be explained under Butane and Pentane. Only those homologues are comparable whose constitutions are similar, as in the case of the normal hydrocarbons. Occurrence. The hydrocarbons of the paraffin series occur naturally in great variety. Thus, methane is exhaled from the earth's crust, as "fire-damp" and as marsh-gas. The next higher homologues are found dissolved in petroleum, which also contains the higher hydrocarbons in large amount. Solid hydrocarbons occur as ozokerite or earth-wax. By the frac- tional distillation of petroleum a large number of these com- MODES OF FORMATION 33 pounds have been isolated. Heptane and hexadecane are also found in the vegetable kingdom. Modes of formation. A. Various members of this series are obtained by the distillation of lignite (Boghead, Cannel coal), wood, bituminous shale, and, in very much smaller quantity, from pit coal. Paraffins are also obtained by dissolving car- bide of iron in acids, and by heating wood, lignite, and coal, but riot graphite, with hydriodic acid. B. From substances containing an equal number of carbon atoms in the molecule. 1. From the halogen alkyls,* C n H 2n+1 X, and, generally speaking, from the substitution products of the hydrocarbons by exchange of the halogen for hydrogen (inverse substitu- tion). This is effected by the action of reducing agents, that is, agents which give rise to nascent hydrogen. Some of the commoner reducing agents " employed for such purposes are sodium amalgam and water, zinc and a dilute acid, zinc and water at 160, the copper-zinc couple in presence of water and alcohol (Gladstone-Tribe), aluminium- or magnesium-amal- gam and alcohol, and one of the most vigorous reducing agents, concentrated hydriodic acid at high temperatures, especially in contact with red phosphorus, which serves to continually renew the hydrogen iodide. (See chapter on Reduction.) 2. From monohydric alcohols, CnR,^ OH, polyhydric alco- hols, C n H 2n (OH) 2 , CJHs^OH)* &c., also from aldehydes, C n H ta+1 'CHO, ketones, C n H ta+1 .COC ll H an . tl , and other com- pounds containing oxygen, by heating with hydriodic acid and red phosphorus at relatively high temperatures. In all these reactions the oxygen is ultimately removed as water. 3. From hydrocarbons poorer in hydrogen, i.e. unsaturated hydrocarbons (see these), by the addition of hydrogen; e.g. ethane from ethylene or acetylene and hydrogen, either in presence of platinum black or finely-divided nickel or by heat- ing the mixture of gases to 400-500. Also by heating with hydriodic acid (Kraffl\ or by addition of halogen or halogen hydride, and exchange of the halogen for hydrogen, according to 1. Thus: = C 2 H 6 , f C 2 H 4 + HBr = C 3 H 6 Br, C;HI O + 2HI = C 6 H 12 + I 2 ; \C 2 H 6 Br + 2H = C 3 H fl + HBr. * The monovalent residues, C n Ha n .M, methyl, ethyl, &c., which are at the same time the radicals of the monohydric alcohols, CnHjn + iOH, are fre- quently termed alkyl groups, (B480) C 34 L HYDROCARBONS 4. By decomposing the organo-zinc compounds (zinc-alkyls) with water (Fmnkland) Zn(C 2 H 6 ) 2 + 2H 2 = Zn(OH) 2 + 2C 2 H fi . Or more readily by decomposing Grignard's organo-magnesium compounds with water. Thus ethyl iodide and magnesium, in presence of dry ether, yield ethyl magnesium iodide, C 2 H 6 MgI, and this with water evolves ethane: C 2 H 6 .Mg.I-t-H.OH = C 2 H 6 -f OH-Mg.L C. From acids containing more carbon, with separation of carbon dioxide. Thus, by heating acetate of calcium with soda-lime, methane and carbonic acid are formed: (CH 3 COO) 2 Ca + Ca(OH) 2 = 2CH 4 + 2CaCO s . In the case of the acids of higher molecular weight, this separation of carbonic acid is conveniently effected by heating with sodic ethoxide. D. By the combination of two radicals containing a smaller number of carbon atoms. 1. By the action of sodium upon the alkyl iodides in ethereal solution (Wurtz)\ or by heating with zinc in a sealed tube (Frankland): 2 CH 3 I -f 2 Na = C 2 H G + 2 Nal. By this method also two different radicals can be combined, e.g. C 2 H 5 I + C 4 H 9 I give C 2 H 5 + C 4 H 9 = C 6 H 14 , ethyl-butyl (Wur&s "Mixed Radicals"). 2. By the electrolysis of solutions of the potassic salts of fatty acids (Kolbe, 1848). The anions, for example, CH 3 .COO, when discharged at the anode, break up into CH 3 and C0 2 , and two of the CH 3 groups immediately combine to form a molecule, CH 3 CH 3 , viz. ethane. The hydrogen is here evolved at the cathode, and the hydrocarbon at the anode; the carbon dioxide is to a large extent retained in the solution. Methane, CH 4 (Folta, 1778). Occurrence. As an exhalation from the earth's crust, more especially at Baku in the neigh- bourhood of the Caspian Sea (the "Iloly Fire" of Baku)j from the large gas wells at Pittsburg, in North America, and in numerous other places; in the exhalations from mud volcanoes, for instance at Bulganak in the Crimea, where the gas is almost pure methane (Bunsen); and as pit gas or "fire-damp" in mines, where, when mixed with air, it is apt to cause explosions. As marsh-gas, together with carbon dioxide and nitrogen, METHANE 35 by the decomposition of organic substances under water; further, by the fermentation of cellulose, e.g. by river mud, by means of Schizomycetes (fission-fungi). It is also found in rock-salt (the Knistersalz of Wieliczka), and in the human intestinal gases (up to 57 per cent CH 4 after eating pulse). The illuminating gas obtained by the destructive distillation of coal contains about 40 per cent methane. Modes of preparation. 1. Methane is formed synthetically by the direct union of carbon and hydrogen. Pure sugar carbon freed from all traces of hydrogen by treatment with chlorine is heated in a current of dry hydrogen in a porcelain tube, and the issuing gas is found to contain one per cent of methane (Bonezud Jerdan, J. C. S., 1897, 41; 1901, 1042; Pring, 1910, 489; Pring and Fairlie, 1911, 1796, 1912, 91); and is also formed by the decomposition of ethane, ethylene, and acety- lene at moderate temperatures (Bone and Coward, 1908, 1197). 2. When carbon monoxide and hydrogen are passed over reduced nickel at 200-250. The nickel acts as a catalytic agent, and apparently undergoes no change. Carbon dioxide may be substituted for the monoxide. (Sabatier and Sender ens.) The reactions are: CO + 3H 2 = CH 4 + H 2 and C0 2 + 4H 2 = CH 4 + 2H 2 3. By leading sulphuretted hydrogen and carbon bisulphide vapour over red-hot copper (Saihelot); CS 2 -f 2H 2 S -f 8Cu = CH 4 -f 4Cu 2 S. Steam may be substituted for the sul- phuretted hydrogen. 4. It is usually prepared by heating anhydrous sodic acetate with baryta, or, less advantageously, with soda-lime (cf. p. 34), ethylene, C 2 H 4 , and hydrogen (up to 8 per cent) being formed at the same time. 5. Pure methane is obtained from magnesium methyl iodide and water, CH^-Mg-I + H-OH = CH 4 + OH-Mg-I; also (see B, 1) by the reduction of methyl iodide, CH 3 I, e.g. in alcoholic solution by means of zinc in the presence of pre- ni-rv!4ri4-<->s3 f.f\-r\-r\r\m /V./-k ffl n J0ir\m a^ / 7 T /n/7n> " r~!rrnpT_7.Tnp. liOlTnlft i t"*" cipitated copper (the Gladstone-Tribe "Copper-zinc Couple"), also by the inverse substitution of chloroform, CHCl^ or carbon tetrachloride, CC1 4 . Properties. -It is a gas with a dersity = 8 (H = 1), and is condensed under a pressure of ^0 atmospheres at 0. It boils at 164, and solidifies at 186. Absorption coefficient in cold water about 0'05, in cold alcohol 0'5. It burns with a 36 I. HYDROCARBONS pale and only faintly luminous flame, yielding carbon dioxide and water, and when mixed with air or oxygen in certain pro- portions forms an explosive mixture. It is decomposed by the electric spark into its elements, and a similar decomposition occurs when the gas is led through a red-hot tube; but there are formed at the same time C 2 H 6 , C 2 H 4 , C 2 H 2 , and, in smaller quantity, C 6 H 6 , benzene, C 10 H 8 , naphthalene, and other pro- ducts. The first three hydrocarbons just mentioned, ethane, &c., behave similarly. Combustion of Hydrocarbons. When methane and hydro- carbons generally are burnt or exploded with excess of air or oxygen, the final products are carbon dioxide and water vapour, and the reaction is generally represented, e.g., by the equation CH 4 -f 2 2 = C0 2 -f 2 H 2 0. This undoubtedly represents the final products which are formed, and also their relative amounts, but does not give an idea of the mechanism of com- bustion. Numerous investigators have conducted experiments on combustion, especially on combustion in the presence of limited amounts of oxygen. The conclusion was first drawn that with a defective supply of oxygen the hydrogen is oxi- dized in preference to the carbon. Somewhat later, Kersten (1861) suggested the preferential burning of the carbon, since when ethylene is exploded with its own volume of oxygen, carbon monoxide and hydrogen are the chief products. (Cf. Smitkdls, J. C. S. 1892, 61, 220.) The recent work of Bone and others on the slow combustion of methane, ethane, ethylene, and acetylene (J. C. S. 1902, 535; 1903, 1074; 1904, 693, 1637; Proc. 1905, 220; B. A. Eeport, 1910, 469), shows that by passing a mixture of methane and oxygen in a continuous stream through a tube filled with porous material (pot or magnesia), at a fixed temperature between 350 and 500, appreciable amounts of formaldehyde are obtained. Gaseous products are also obtained, but these are probably due to secondary reactions, e.g. either the further oxidation of the aldehyde to carbon monoxide, carbon dioxide, and steam, or the thermal decomposition of the aldehyde into carbon monoxide and hydrogen. Thus : ^^*CO + H a + H 2 CH 4 > CH 2 (OH) a OH, :0+H a O < C^^Thermal decomposition .Oxidation * CO, 4- H 2 + H 2 Thermal decomposition. ETHANE 37 By the expression thermal decomposition is meant that at the temperature mentioned the aldehyde is unstable, and imme- diately decomposes into the simpler products, CO and H 2 . Ethane behaves similarly, and the reactions can be repre- sented by the following scheme : CH 3 .CH 3 CH 3 .CH(OH) 2 -* CH 3 .CH:0 + ELO o a o, OH.CH 2 .C0 2 H i CH 2 :0-hCO + H 2 0. Secondary reactions are the thermal decompositions of the formaldehyde into CO and H 2 ,. and of the acetaldehyde into CH 4 and CO. In reality some 80 per cent of the ethane can be collected as formaldehyde. With ethylene the reactions are probably CH 2 :CH 2 OH.CHrCH-OH 2CH 2 :O H-CO 2 H , O 2 00 OH-CO-OH, and the thermal decomposition products of the formaldehyde, formic acid, and carbonic acid, viz. H 2 , CO, C0 2 , H 2 0. It is thus obvious that at the temperatures mentioned (350- 500) combustion consists primarily in the addition of oxygen and the production of hydroxylic compounds, which then yield aldehydes. It is highly probable that reactions of a similar nature occur during explosive combination ana detonation at high temperatures (B. A. Report, 1910, 492). Ethane, C 2 H 6 , occurs in crude petroleum and constitutes the gas of the Delamater gas well in Pittsburg, and is there utilized for technical purposes. Preparation. By the electrolysis of acetic acid (Kolbe, 1848), and therefore formerly called " methyl " since it was supposed to be CH 3 ; subsequent molecular-weight determinations proved it to have the double formula C 2 H 6 . It is also obtained from, ethyl iodide, alcohol, and zinc dust, or from zinc ethyl (Frank- land), hence the name "ethyl hydride". "Ethyl hydride" and " methyl ", which were formerly supposed by FranHand and Kolbe to be different substances, were proved to be identical by Schorlemmer in 1863 by their conversion into C 2 H 5 C1, which may be prepared from both in exactly the same way. It is a gas which can be condensed under a pressure of 46 atmospheres at 4, and is somewhat more soluble than 88 L HYDROCARBONS methane in water and alcohol. It burns with a faintly- luminous flame. Propane, C 3 Hg, and the two butanes, C 4 H 10 , are also gaseous at the ordinary temperature, and are present to a certain ex- tent in crude petroleum. Theoretically propane can exist in only one form, represented by the constitutional formula CH 3 CH 2 CH 3 , as this is the only manner in which three carbon and eight hydrogen atoms can be grouped up if we assume that the carbon atoms are tetravalent and the hydrogen atoms monovalent. ISOMERISM, NOMENCLATURE, CONSTITUTION To determine whether the next homologue, C 4 H 10 , can theoretically exist in more than one modification, we can start a /3 a with propane, CH 3 CH 2 'CH 3 , and replace one of the eight hy- drogen atoms by "a methyl group. It is obvious that we can obtain two distinct compounds according to whether we re- place one of the six terminal hydrogens (a) or one of the central hydrogens (/?). The two compounds would have the respective formulae CH 3 .CH 2 .CH 2 .CH 3 and and are known as normal butane and iso-butane (or trimethyl methane). Two compounds having the formula C 4 H 10 are actually known, and their constitutional formulae derived from their methods of formation agree with the two formulae CH 3 CH 2 CH 2 -CH 3 and (CH 3 ) 2 : CH CH 3 , as the ^compound may be obtained by the action of zinc on ethyl iodide, CH 3 CH 2 T, and the ^so-compound by the reduction of tertiary butyl iodide, (CH 3 ) 2 :CI.CH 3 . All the succeeding hydrocarbons can, according to theory, exist in various isomeric modifications. The number of modi- fications possible can be derived in exactly the same manner as already described for the butanes. As an example, take the hydrocarbons C 5 H 12 , the pentanes. a /3 B a Starting with n-butane, CH 3 CH 2 'CH 2 -CH 3 , and replacing one H atom by a CH 3 group, we can get either (1) CH 3 .CH a .CH 2 .CH 2 .CH 3 or (2) NOMENCLATURE 3$ according as we replace an H atom in the a or ft position. Starting from iso-butane, We can similarly get :'' (3) >CH.CH 2 .CH s or (4) but formulae (2) and (3) are identical, and the three isomerides possible are therefore CH 3 .CH 2 -CH 2 .CH 2 .CHo, (CHA>:CH. CH 2 .CH 3 and (CH 3 ) 2 :C:(CH 3 ) 2 . Of hydrocarbons with six carbon atoms, five isomers are possible, and they are all known. Of the nine possible heptanes, C^H 16 , the existence of five has already been proved. The number of theoretically possible isomers increases very rapidly with the number of carbon atoms, so that, according to Cayley, 802 isomeric hydrocarbons of the formula C 13 H 28 are possible. Of these isomers only one can be normal, i.e. can have a single chain of carbon atoms, in which each of the two terminal carbon atoms is combined with three atoms of hydrogen, and all the middle ones with two, according to the formula, CEL (CH 2 ) n .CH 3 . A convenient Nomenclature for the more complicated paraffins is arrived at by making methane the starting-point for all of them, that carbon atom from which the branching chain ema- nates being considered as originally belonging to CH 4 , in which the hydrogen atoms are supposed to be wholly or partially re- placed by hydrocarbon radicals, thus: = dimethyl-ethyl-methane. The names of the well-known lower hydrocarbon radicals (alkyls) are also frequently used as a basis; for instance, the group (CH 3 ) 2 CH is termed isopropyl (see Isopropyl Alcohol), hence the compounds: : di-isopropyl. The boiling-points of the normal hydrocarbons are alway* 40 I. HfJJiiOC ARSONS higher than those of the isomers; indeed the boiling-point becomes lowered continuously the more the carbon atom chain is branched, i.e. the more methyl groups are gathered together in the molecule. The Constitution of the higher paraffins can in most cases only be arrived at with certainty from their synthetical formation (e.g. normal butane and hexane), or from their chemical rela- tion to oxygenated derivatives whose constitution is already known, especially to the ketones and acids. (See Ketones.) If, for instance, by the action of PC1 5 upon acetone, for which the constitution CH 3 COCH 3 is proved, the substance CH 3 CClg CH 3 (acetone chloride) be formed, and this be then treated with zinc methyl, the resulting hydrocarbon, a pentane, will have the constitution (CH 3 ) 4 C: = ZnCl 2 + (CH 3 ) 2 :C:(CH 3 ),. As a second example, we have w-hexane, which can be ob- tained by the action of metals upon w-propyl iodide, as repre- sented by the equation : 2CH 3 .CH 2 .CH 2 I + Zn = ZnI 2 The system of nomenclature suggested by the International Congress at Geneva is as follows: The normal paraffins re- tain their present names. Thus hexane means the compound CH 3 (CH 2 ) 4 CH 3 . In the case of those with branching chains the longest normal chain gives the name, the branches being regarded as substituents, and the position of substitution being indicated by the successive numbering of the atoms of the carbon chain (the carbon atom which is nearest to the point of ramification is numbered 1; should there be more than one branching say, a longer and a shorter then No. 1 begins with the end carbon atom which stands nearest to the shorter branching). Trimethyl-methane is therefore called 2-methyl- propane; dimethyl-ethyl-methane, 2-methyl-butane ; and tetra- methyl-methane, 2 : 2-dimethyl-propane. The following paraffins have been obtained from crude petroleum: n- and eso-pentane, 7i-hexane and an isomer, and n-heptane, all these being present in the so-called " gasoline ", which is obtained by the distillation of petroleum, and is used for carburetting coal-gas; further, normal Heptane, n-Octane,* n-Nonane, and 7i-Decane, besides an isomer of each, and in * The petroleum ether and ligroin of commerce consist principally of the hydrocarbons C 6 H 14 , C7H 1G , and C 8 H 18 . PETROLEUM 41 addition to these (as also from the distillation of cannel and Boghead coal), a large number of the higher hydrocarbons. In all probability these products are not chemical individuals, but mixtures of homologues and isomers standing very near to each other, as is shown by a comparison with the artificially- prepared normal hydrocarbons. P. Krafft has prepared those normal hydrocarbons from C n H 24 to C 35 H 72 , which are mentioned in the table on p. 30, from the acids C^, C 14 , C 16 , and C 18 of the acetic acid series (see these), for which the normal constitution, i.e. non-branching carbon chain, has been demonstrated; and also from the ketones, C n H 2u O, which are obtained by subjecting the barium salts of these acids to dry distillation, either alone or together with acetate or heptoate of calcium; and which, as a consequence of their mode of formation, yield normal hydrocarbons. (See Ketones.) Krafft has further isolated the normal hydro- carbons C ]r H 36 to C 23 H 48 , also C 24 H 50 , C 26 H 54 , and C^EU, by subjecting the paraffin obtained from lignite to fractional dis- tillation in vacua. These are, from about C 16 H 34 (m.-pt. 18) on, solid at the ordinary temperature. When distilled under atmospheric pressure, or heated with AlBr 3 + HI, the higher hydrocarbons partially decompose into lower ones of the formulae CJSan+a an d C n H to ; this process is known as "cracking". But they may be distilled in a vacuum, whereby their boiling-points are reduced by 100 or more. (See table.) Petroleum, Mineral Oils. These are probably produced by the decomposition of animal or vegetable organisms* (Engler, C. C. 1906, II, 1017), and are found between Pittsburg and Lake Erie in America; between Lake Erie and Lake Huron in Canada; in Hanover, Holstein, and Elsass in Germany; in Boryslaw in Galicia; in the Crimea; in the Caucasus; in Borneo, &c. The American oil consists mainly of paraffin hydrocarbons, whereas the Eussian oil contains large quantities of hydrocarbons of the general formula CJl,^. These latter have been shown to be closed- chain compounds, they are known as naphthenes, and are isomeric with the olefines. The American and Russian oils are worked up on a large scale for the preparation of commercial products. The crude petroleum is a thick, oily liquid of dark colour and sp. gr. 0'8 to 0-92. It is usually washed with alkalis and sulphuric acid, * This view is supported by the fact that many paraffin oils have a slight optical activity. 42 I. HYDROCARBONS and then subjected to fractional distillation. The fraction 50-60 is termed petroleum ether or petrol, the fraction 70-90 is termed benzoline or benzine, ligroin is the fraction 90-120. Burning oil is the fraction 150-300, and from the higher frac- tions are obtained lubricating oils, vaseline, and paraffin-wax. Paraffin- Wax, obtained by Eeichenbach in 1830 from wood tar, is got by the distillation of lignite or peat. It also is a mixture of many hydrocarbons, about 40 per cent of it con- sisting of the compounds C 22 H 46 , C 24 H 50 , CggH^, and C 28 H 58 . Liquid Paraffin (Reichenbach's " Eupion ") and the butter-like Vaseline are high -boiling distillation products of lignite or petroleum, and the same applies to many lubricating oils. Ozokerite, green, brown, and red, and of the consistency of wax, melting-point 60-80, is a natural paraffin found at Boryslaw in Galicia, at Tscheleken near Baku (also called Neftgil), on the Caspian Sea, and forms the ceresine of com- merce when bleached. Asphalt, or Earth Pitch, found in India, Trinidad, Java, and Cuba, is a transformation product of the higher-boiling mineral-oils, produced by the action of the oxygen of the air just as paraffin absorbs oxygen and becomes brown upon pro- longed heating in the air. It is used for cements and salves, and in asphalting, photo-lithography, &c. B. defines OP Hydrocarbons of the Ethylene Series (Alkylenes): CJI^ There are two series of hydrocarbons of the general formula CnHan, the members of which differ from the corresponding paraffins by containing two atoms of hydrogen less in the molecule. The one series is that of the Olefines, of which ethylene, C<>H 4 , is the first member; the other is that which contains Trimethylene, Tetramethylene, Hexamethylene, &c. (Cf. Polymethylenes.) The properties exhibited by these two series are so different that different constitutions must be accorded to them. The olefmes form additive compounds with exceptional facility, being thus converted into the paraffins or their derivatives; from this the conclusion is drawn that, like the latter, they contain an open carbon chain. The names given to the hydrocarbons are similar to those for the paraffins, except that the termination ane is replaced by ene, or often by yUne. OLEFINES SUMMAKY 43 Melting-point. Boiling-point. Ethylene CUL 169 .10*? Propylene CH 48 Butylene (3>: fa G.HJ 8 -5 4-1 Amylene (5) ... 17 C,H in * -6 _|_39 OK 68 Heptylene . QK Octylene E 124 Nonylene CalLo 153 Decylene.. .. r H 172 TJndecylene . . . . CJI 195 Dodecylene 31 {96t Tridecylene . . . 3 2 I 2 2 j 233 Tetradecylen e 12 {127 Pentadecylene .. . FT 247 Hexadecylene (Cetene).. Octadecylene . . . CicHga C 18 H,, +4 18 / 274 \{155 (179 Eicosylene P 18 rf 3n Cerotene tiX 58 Melene . . 62 The general formula C n H 2n for this series indicates that each member differs from the corresponding member of the paraffins by two hydrogen atoms. In their physical properties they resemble the methane homologues very closely. C 2 H 4 , C 3 H 6 , and C^Hg are gases, C 5 H 10 a volatile liquid, the higher members liquids with rising boiling-point and diminishing mobility, while the highest are solid and similar to paraffins. The boiling-points of members of both series containing the same number of carbon atoms, and whose constitutions are comparable, lie very close together, but the melting-points of the olefines are somewhat the lower of the two; e.g. C ]6 H, 4 , m.-pt. 21, b.-pt. {157, and C 16 H 32 , m.-pt. 4, b.-pt. {155. * The melting- and boiling-points given from C 5 Hi on, are those of the normal hydrocarbons, t { signifies boiling-point under 15 mm. pressure. 44 I. HYDROCARBONS Most of the olefines are readily soluble in alcohol and ether, but insoluble in water, only the lower members dissolving slightly in the latter. The specific gravities of the normal olefines, determined at the melting-points, rise from about O63 upwards, and approach with increasing carbon to a definite limit, viz. about 0'79. In their chemical relations, the olefines differ materially from the paraffins. Most of their special chemical characteristics are undoubtedly due to the presence of a double or olefine bond in the molecule, e.g. ethylene, CH 2 :CH 2 . (Cf. Con- stitution of Olefines.) (a) They combine readily with nascent hydrogen, with chlorine, bromine, iodine, and their hydracids, fuming sul- phuric acid, hypochlorous acid, nitrous acid, and, generally speaking, with two monad atoms or monovalent groups, whereby members of the methane series or their derivatives ensue; hence their name of " Unsaturated Hydrocarbons". - as- = C 2 H 6 (S0 4 H). In the formation of these additive compounds the double bond present in the molecule becomes converted into a single bond, and the two monovalent groups (e.g. Br, H,.OH, &c.) add themselves on to the two carbon atoms between which the double bond previously functionated, e.g. CH 2 :CH 2 + Br 2 gives CH 2 Br'CH 2 Br. Thus by the addition of bromine to an olefine the two bromine atoms must always be attached to two adjacent carbon atoms. (Cf. Polymethylene Hydrocarbons.) Combination with hydrogen is sometimes effected, e.g. in the case of ethylene, by the aid of platinum black at the ordinary temperature, by means of finely-divided nickel at a higher temperature, or by heating the olefines or their dichlor-, &c., additive products with fuming hydriodic acid and phosphorus. (Cf. Modes of Formation of the Saturated Hydrocarbons.) Ethylene chloride, C 2 H 4 C1 2 , obtained by the combination of ethylene with chlorine, was formerly called the oil of the Dutch chemists, hence the name of "Olefines" for the whole class of hydrocarbons C n H 2n (Guthrie). Chlorine adds itself on more easily than iodine, but hydro- chloric acid less readily than hydriodic, bromine and hydro- MODES OF FORMATION 45 bromic acid standing midway. When a halogen hydride is used, the halogen attaches itself to that carbon atom to which the smaller number of hydrogen atoms are already united, *e.g. CH 3 .CH:CH 2 + HI = CH 3 .CHI.CH 3 . Particular olefines, e.g. isobutylene, also combine slowly with water to alcohols under the influence of dilute acids. Ethylene combines with fuming sulphuric acid at the ordinary temperature, and with the concentrated acid at 160-170. Amylene forms with nitrogen tetroxide, N 2 4 , amylene nitrosate (A. 248, 161); nitrogen trioxide and nitrosyl chloride also unite directly with the olefines. (b) They readily polymerize, especially in presence of sul- phuric acid or zinc chloride. "Thus amylene, C 5 H 10 , in presence of sulphuric acid yields the polymers C 10 H 20 , C, H 30 , and C 20 H 40 ; and tertiary butyl alcohol, warmed with acid of a definite strength, di-isobutylene. (c) Unlike the paraffins, they are readily oxidized by KMn0 4 or Cr0 3 , but not by cold HN0 3 . In this reaction, two hydroxyl groups are added to the molecule of the olefine if a dilute (1 per cent) solution of 'per- manganate is used, and a dihydric alcohol (a glycol) is formed. CH 2 :CH 2 T* OH.CH 2 .CH 2 .OH. But if stronger solutions are used, or if chromic anhydride is employed, the molecule of the olefine is ruptured at the point where the double bond exists and a mixture of simpler acids or ketones is obtained. The readiness with which unsaturated compounds discharge the colour of acidified permanganate is frequently made use of as a qualitative test for such compounds. The "official name" (p. 40) of the olefines is formed by replacing the last syllable " ane " of the paraffins by " ene ". The position of the double bond is denoted by the number of the carbon atom from which it proceeds. In a branching chain the numbering is the same as in the case of the corre- sponding saturated hydrocarbons; in a normal chain it begins at the end carbon atom which is nearest to the double bond. Example: * 2 8 * is 4-methyl-2-pentene. Modes of formation. (a) Together with paraffins by the destructive distillation of many substances, such as wood, *Cf. Michael, J. pr. 1888, [ii] 37, 524; 1903, 68, 487; B. 1906, 39, 2138, 46 I. HYDROCARBONS lignite, and coal, and also by the distillation of the higher paraffins (process of "cracking", p. 41); illuminating gas con- sequently contains the olefines C 2 H 4 , C 8 H 6 , C 4 H 8 , &c. (b) By abstraction of water from the alcohols, CnH^^OH, by heating them with sulphuric acid, phosphorus pentoxide, zinc chloride, anhydrous formic acid, syrupy phosphoric acid, &c. When sulphuric acid is used, an alkyl-sulphuric acid, e.g. ethyl hydrogen sulphate, C 2 H 5 S0 2 OH, is first formed, and this decomposes upon further warming into alkylene and sul- phuric acid. This method is especially applicable in the case of the lower homologues. Many alcohols yield olefines when heated alone, or with finely divided solids (Chap. XLIX). The palmitic esters of the higher alcohols, when distilled under somewhat diminished pressure, yield palmitic acid and an olefine. (c) By heating the halogen compounds C n H 2n+1 X with alco- holic potash, or by passing their vapour over red-hot lime or hot oxide of lead, &c. ; sometimes by simple distillation : C 6 H n I + KOH = C 6 H 10 + KI + H 2 0. The iodine and bromine compounds are particularly suited for this. The reaction may be regarded as the elimination of a molecule of halogen hydracid from the molecule of the com- pound, the halogen coming from the one carbon atom and the hydrogen from an adjacent. (Cf. also Nef, A. 1901, 318, 3.) (d) Sometimes from the haloid compounds CnH^X, by ab- straction of the halogen,* e.g. ethylene from ethylene bromide by treatment with zinc, magnesium, or zinc dust and alcohol: C 2 H 4 Br 2 + Zn = C 2 H 4 + ZnBr 2 . (e) By the electrolysis of potassic salts of dibasic acids 01 the succinic acid series; thus succinic acid itself yields ethy- lene: C 2 H 4 (COOH) 2 = C 2 H 4 + 2C0 2 + H 2 . The complex anion CO CH 2 CH 2 CO 0, when discharged decomposes into ethylene and carbon dioxide. Constitution of the Olefines. For ethylene the following for mulae may be given: CH 3 CH 2 - CH 2 * Only when the halogen atoms are attached to adjacent carbon at*#is. ]] METHYLENE U 47 . ^_^v ft t*W 1^0^ In the formulae I and II, two free carbon bonds or valencies are assumed in the ethylene molecule. Formula III follows from the assumption that the bonds which are not used up in attaching the hydrogen atoms to carbon are used in uniting the carbon atoms themselves. Now the ethylene bromide which is formed by the addition of bromine to ethylene has, for reasons which will be given under that compound, the constitution CH 2 BrCH 2 Br, and likewise the compound obtained by the addition of C10H (i.e. Cl and OH), viz. glycol chlorhydrin, the constitution CH 2 C1CH 2 OH; consequently formula I, according to which these substances would have the constitutions CH 3 CHBr 2 and CH 8 .CHC1(OH), is excluded. Formula III is more probable than formula II: (a) Since methylene, CH 2 :, appears to be incapable of existence; all attempts to isolate it have yielded ethylene, C 2 H 4 (see below), so that free valencies attached to the carbon atom probably cannot exist. (b) Because the free affinities to be assumed according to II are never found singly (which should in that case be possible), but invariably in pairs only, and indeed only on neighbouring carbon atoms. This is proved from the constitution of the compounds obtained by the addition, for instance, of Br 2 . Unsaturated compounds containing only one carbon atom, and unsaturated hydrocarbons containing an odd number of hydrogen atoms, are unknown. It is therefore to be concluded that in ethylene and its homologues a double carbon bond, corresponding with formula III, exists. By this term " double bond " is not, however, to be under- stood a closer or more intimate combination. The defines, on the contrary, are more readily oxidized than the paraffins, being thereby attacked at the point of the double bond. Other properties, especially physical ones, also give indications that a double bond between two carbon atoms is looser, and therefore more easily broken, than a single one. (Cf. Bruhl, A. 211, 162.) 1. Methylene (Methene), CH 2 , does not exist. Numerous attempts to prepare it, e.g. by the withdrawal of hydrogen and chlorine from methyl chloride, or of iodine from methylene jodide, have invariably yielded ethylene, thus: 2CH 3 C1 -2HC1 = C 2 H 4 . / \~\ ^"Nl .* - z- 48 I. HYDROCARBONS Here the two resulting CH 2 -residues have united together, in the same way as the two methyl-groups coalesced to ethane (p. 34). 2. Ethylene (Ethene), olefiant gas, CH 2 :CH 2 . This compound was discovered in 1795 by four Dutch chemists. Its formula was established by Dalton. Illuminating gas generally contains 4 to 5 per cent of ethy- lene. For formation from elements see Pring and Fairlie, J. C. S. 1911, 99, 1806. It is usually prepared by heating alcohol with excess of concentrated sulphuric acid, with addi- tion of sand, a mixture of equal portions of the two liquids being subsequently dropped into the evolution flask; sulphur dioxide, &c., are produced at the same time by secondary re- actions. A better method is to heat alcohol with syrupy phosphoric acid at 200 (Newtli). Small quantities can be conveniently prepared from ethylene bromide and zinc or magnesium. It is further formed by heating ethylidene chloride, CH 3 -CHC1 2 , with sodium. It may be liquefied at under a pressure of 44 atmos., is very slightly soluble in water and alcohol; burns with a luminous flame, and forms an explosive mixture with oxygen. When rapidly mixed with two volumes of chlorine and set fire to, it burns with a dark-red flame, with formation of hydro- chloric acid and deposition of much soot. It is converted at a red heat into methane, CH 4 , ethane, C 2 H 6 , acetylene, C 2 H 2 , &c., with separation of carbon. (See p. 36.) It combine! with hydrogen in presence of spongy platinum to ethane, C 2 H 6 . " 3. Propylene (Propene), C 3 H 6 , CH 2 :CH-CH 3 . Only one olefine, C 3 H 6 , is theoretically possible and only one is known, viz. methylethylene. It can be prepared from isopropyl iodide and caustic potash, or by heating glycerol with zinc dust. It is isomeric with trimethylene (see Polymethylenes). 4. Butylene, C 4 H 8 . Three butylenes are possible according to theory, and three are known. All of them are gaseous, their boiling-points lying between 6 and +3. Butylene and pseudo-butylene are derived from normal butane, and iso- butylene from isobutane, since they severally combine with H 2 to form these hydrocarbons. The first, a-butylene, is prepared from normal; the second, /3-butylene, from secondary; and the third, y-butylene, from tertiary butyl iodide, by the action of caustic potash upon these; the last can also be obtained from isobutyl alcohol and sulphuric acid. The isomerism of the two V 'a ACETYLENE HYDROCARBONS 49 butylenes derived from normal butane is explained by the assumption of a double bond at different points, thus: CH 2 : CH . CH 2 CH 3 CH 3 CH : CH CH 3 a-butylene (l-butene) /3-butylene (2-butene). Isobutylene has the formula (CH 3 ) 2 C : CH 2 (methylpropene). The behaviour of these isomers upon oxidation is in accordance with the above formulae, the oxidation always taking place at the point of the double bond. The butylenes are isomeric with tetra-methylene (cydo- butane, see Polymethylenes). 5. Amylene, C 5 H 10 . A large number of isomeric amylenes are known, among them being Amylene (b.-pt. 35), which is obtained, together with an isomer, Iso-amylene, by heating ordinary amyl alcohol with chloride of zinc. For it the con- stitutional formula (CH 3 ) 2 C : CH CH 3 ( = trimethylethylene) is assumed. This is known in the pure form under the name of "pental". The higher defines of normal constitution, with 12, 14, 16, and 18 atoms of carbon, have been prepared by Kraft accord- ing to method b. Cerotene and Melene (m.-pt. 62) are obtained by the distil- lation of Chinese wax and bees'- wax respectively. They are like paraffin in appearance, and are only sparingly soluble in alcohol. C. Hydrocarbons, C n H 2n _ 2 : Acetylene Series The hydrocarbons of this series again differ from those of the preceding by containing two atoms of hydrogen less. In physical properties they closely resemble both the latter and those of the methane series; thus the lowest members up to C,H 6 are gaseous, the middle ones liquid, and the highest solid, and in their melting- and boiling-points they do not differ to any extent from those of the other series with an equal number of carbon atoms. The specific gravities of the normal hydrocarbons C 12 , C 14 , C 16 , and C 18 , at the melting- point, gradually approach with increasing carbon to a definite limit (0-80), and are somewhat higher than those of the corre- sponding members of the ethylene series throughout. ^ Constitution. Upon grounds similar to those which have already been explained under ethylene, the constitutional for- mula for acetylene, C 2 H 2 , is assumed to be CH-CH, according to which the carbon atoms are joined together by a triple bond. ( B 480 ) P 50 I. HYDROCARBONS For a compound C 3 H 4 , the two following constitutional for- mulae are possible : CH : C CH 3 (allylene) and CH 2 : C : CH 2 (allene). As a matter of fact, two hydrocarbons C 3 H 4 do exist, only one of which, allylene, yields metallic compounds. It is therefore to be considered the true homologue of acetylene, containing a triple bond, according to the first of the two above formulae, while to allene the second formula, with the two double bonds, is to be ascribed. The constitution of the tetrabromopropanes, which are formed from these by the addition of bromine, agrees with this conception. In their chemical relations the acetylenes stand nearer to the olefines than to the paraffins, in so far that they are un- saturated and therefore capable of forming additive products. 1. A molecule of an acetylene can combine either (a) with two atoms of hydrogen or halogen, or with one molecule of halogen hydride, to olefines or their substitution products, thus : CH:CH + 2H = CH 2 :CH 2 CHiCH + HBr = CH 2 :CHBr (vinyl bromide) CH:CH + Br 2 = CHBnCHBr; ' or (b) with four atoms of hydrogen or halogen, or two mole- cules of halogen hydride, to paraffins or paraffin substitution products, thus: CH 3 .C:CH + 4H = CH 3 .CH 2 .CH 3 (in presence of platinum black) CH : CH + 2 Br, = CHBr 2 CHBr 2 CH 3 -C:CH + 2"HI = CH 3 .CI 2 .CH 3 . Like many of the olefines, various members of this series combine with water under the influence of dilute acids, thus allylene, C 3 H 4 , gives acetone, C 3 H 6 0; and acetylene, C 2 H 2 , gives crotonic aldehyde, with intermediate formation of acetic aldehyde. The combination with water may be accomplished (a) by the action of sulphuric acid when, as in the case of the olefines, alkyl hydrogen sulphates are formed as intermediate products; (b) by means of mercuric chloride solution; or (c) by directly heating the hydrocarbon with water at 300 in sealed tubes. HgCl 2 and other mercury salts also induce such hy- dration : CH:CH-fH 2 O = CH 3 .CHO CH 3 -C:CH + OH 2 = CH 3 .CO-CH 3 . FORMATION OF ACETYLENE HYDROCARBONS 51 2. Many of the acetylene hydrocarbons are readily poly- merized; thus, acetylene is transformed into benzene when led through a red-hot glass tube. This is an important syn- thesis of benzene: 3C 2 H 2 = CJH,. At the same time the compounds C 8 H 8 , 10 H 8 , &c., are formed. Similarly allylene, C 3 H 4 , gives mesitylene, C 9 Hi 2 , in contact with sulphuric acid and a little water. (See Ben- zene Derivatives.) 3. Acetylene and some of its homologues react even at the ordinary temperature, in a manner which is peculiar to them, with an ammoniacal solution of cuprous or argentic oxide, to form reddish - brown or yellow-white precipitates, e.g. CCu: CCu; CAgiCAg; CH 3 C:CAg, &c., which are explosive, and which are decomposed by acids, such as HC1, with regeneration of the hydrocarbon. The hydrogen of acetylene can be replaced by potassium or sodium; thus, when the hydrocarbon is heated with sodium, the compounds C 2 HNa and C 2 Na 2 are obtained. These are decomposed by water or acids with evolution of acetylene. All the hydrocarbons CJE^^ do not, however, give such metallic compounds, but only the true homologues of acetylene containing the grouping C : CH. Hydrocarbons such as allene, CH 2 :C:CH 2 , which do not contain a triple bond, and even acetylene compounds such as CH 3 C C CH 3 , where no hydrogen atoms are attached to the C atoms between which the triple bond is supposed to exist, do not yield these metallic derivatives. In the case of the higher homologues, isomerism may be due either to the difference in position of the triple carbon bond in the molecule, or to the presence and different positions of the two double bonds. The constitution of a compound is fixed by the formation or otherwise of metallic derivatives, and by its behaviour upon oxidation. (See Oxidation of the Butylenes, p. 49.) The official name of the acetylene homologues proper, with a triple carbon-linking, ends in "ine"; that of the isomeric hydrocarbons, with two double bonds, in "diene". Formation. 1. They are obtained, together with the hydro- carbons already described, by the distillation of wood, lignite, coal, &c.; thus illuminating gas contains acetylene, allylene, and crotonylene. 52 I. HYDROCARBONS 2. By treating the haloid, preferably the bromine, com- pounds C n H 2n X 2 and CyB^^X with alcoholic potash or sodium ethoxide (C 2 H 5 ONa): H \ / Br H^C-Cr-H 2HBr = HC:CH. Br/ \H With alcoholic potash, even when excess is used, the re- action tends to stop at the first stage, and a brominated olefine is formed, e.g. vinyl bromide (p. 65) from ethylene dibromide; with sodic ethoxide, the elimination of hydric bromide pro- ceeds more readily. Further, from the unsaturated alcohols, CJE^^'OH, by the separation of the elements of water from them. 3. By the electrolysis of potassium salts of the acids of the fumaric acid series (KekuU). 4. Certain acetylene hydrocarbons, R-CiC-CH 3 , when heated with sodium, pass into the sodium compounds of their isomers, R-CH 2 C:CH; on the other hand, when the latter are warmed with alcoholic potash, the opposite reaction takes place (Faworsky, B. 20, Ref. 781; 25, Ref. 81; 25, 2244). Acetylene (Bibine), C 2 H 2 , was first obtained impure by E. Davy from calcium carbide in 1839, and pure by Berthelot in 1849. Illuminating gas contains 0'06 per cent. It is syn- thesised from its elements, when an electric arc is caused to pass between two carbon poles in an atmosphere of hydrogen (Berthelot), but other hydrocarbons are formed at the same time (Bone and Jerdan, J. C. S. 1901, 1042; cf. also Button and Pring, 1906, 1591). It may be obtained from ethylene bromide and sodium ethoxide solution ; also by the incomplete combustion of many carbon compounds, for instance, when the gas in a Bunsen lamp burns at the base; and from ethane, ethylene, and methane at a red heat, or by the action of the induction spark. (See pp. 36 and 48.) The simplest method of preparation is by the action of water on calcium carbide, the water being allowed to drop gradually on to the carbide : C 2 H 2 . It becomes liquid at 1 under a pressure of 48 atmospheres, burns with a luminous and very sooty flame, and has a peculiar disagreeable smell. Its flame has a high illuminating power- when burnt in specially-constructed burners, and is now largely made use of as an illuminating agent. It dissolves in its own DIPROPARGYL 53 volume of water, and in six times its volume of alcohol; is poisonous, combining with the hsemoglobin of the blood, It is decomposed into its elements with detonation by ex- plosive fulminate of silver, and also by the electric spark, It combines with hydrogen to ethane, when heated with the latter in presence of platinum black, or to ethylene, upon treat ing its copper compound with zinc and ammonia. A mixture of acetylene and oxygen explodes violently when a light is applied to it. Chromic acid oxidizes acetylene to acetic acid, and permanganate of potash to oxalic acid. It combines with nitrogen under the influence of the induction spark to hydro- cyanic acid (see this), and detonates upon being mixed with chlorine, but additive products, e.g. C 2 H 2 C1 2 , can, however, be prepared. As little as ^J<y milligramme of it can be detected by the formation of the dark-red copper compound C 2 Cu 2 . This latter explodes when struck, or when heated to a little over 100. Allylene (Propine), C 3 H 4 , or CH 3 C:CH, can be prepared from propylene bromide, CH 3 CHBr CH 2 Br. It resembles acetylene. Allene (Propadiene), C 3 H 4 , or CH 2 :C:CH 2 , is obtained by the electrolysis of itaconic acid. It is gaseous, and does not yield metallic compounds. Diallyl (Hexa-l : 5 -diene), CH 2 : CH . CH 2 . CH 2 CH : CH 2 , is obtained from allyl iodide, CH 2 :CHCH 2 I, and sodium. ^ Isomeric with these hydrocarbons are certain hydro-deriva- tives of aromatic hydrocarbons, e.g. tetrahydrobenzene, C 8 H 14 ; decahydronaphthalene, C 10 H 18 . (See Aromatic Compounds.) D. Hydrocarbons C n H, 2n- Di-acetylene (Butadiine), C 4 H 2 , or CH-C-C-CH. This is prepared by heating the ammonic salt of diacetylene-dicar- boxylic acid (see this) with ammoniacal copper solution, whereby it is transformed into the cuprous compound of di- acetylene, and then warming this with potassium cyanide. It is a gas of a peculiar odour, which yields a violet-red copper compound and a yellow silver one, the latter exploding upon bromide, and the subsequent elimination of four molecules of hydric bromide from each molecule of the tetra-bromide; b.-pt. 64 II. HALOID SUBSTITUTION PRODUCTS 85. It gives copper and silver compounds, and takes up eight atoms of bromine, &c. It possesses an especial interest, as it is isomeric with benzene. Another isomeride is 2 : 4:-Hexadiine, CH 3 . C i C C : C CH 3 . (B. 20, R. 564.) II. HALOID SUBSTITUTION PRODUCTS OF THE HYDROCARBONS A. Halogen Derivatives of the Paraffins These are to be regarded as paraffin hydrocarbons in which one or more hydrogen atoms have become replaced by one or more halogen atoms. General Properties. Only a few of these compounds, e.g. CH 3 C1, C 2 H 5 C1, and CH 3 Br, are gaseous at the ordinary tem- perature, most of them being liquid, and those with a very large number of carbon atoms in the molecule solid, e.g. cetyl iodide, C 16 H 33 I. The introduction of a halogen atom in any hydrocarbon in place of an atom of hydrogen always tends to raise the boiling-point; the introduction of iodine has the most marked effect, and chlorine the least (cf. Table, p. 56). Such, also, as contain a large number of halogen atoms, e.g. CI 4 , C 2 C1 6 , are solid. Under comparable conditions, the boiling- points of the iodides lie, for each atom of halogen, about 50 (40-60), and those of the bromides about 22 (20-24), above those of the chlorides. The lowest members of the series have, in the liquid form, at first a higher specific gravity than water, e.g. CH 3 I, sp. gr. 2*2, C 2 H 5 Br, sp. gr. 1'47. With an increasing number of carbon atoms, however, they become more like the paraffins, the influence of the halogen diminishes, and they are lighter than water. The halogen substitution products of the hydrocarbons are very sparingly soluble in water, but readily in, and therefore miscible to any extent with, alcohol or ether; they also dissolve in glacial acetic acid. They often possess a sweet ethereal odour, but this becomes less marked with diminishing vola- tility. Most of them are combustible; thus methyl and ethyl chloride burn with a green-bordered flame, while ethyl iodide and chloroform can only be set fire to with difficulty. Many MODES OF FORMATION 55 members of the series containing one or two atoms of carbon produce insensibility and unconsciousness when inhaled, e.g. CHClg, C 2 H 3 C1 3 , C 2 H 5 Br, and C 2 HC1 5 . The liquid iodine derivatives are readily decomposed, and on exposure to light turn deep-brown in colour, owing to the liberation of free iodine, e.g. ethyl iodide liberates iodine and gives C 4 H 10 . In all these compounds the halogen is more firmly bound than in inorganic salts, so that, for instance, when silver nitrate is added to an aqueous solution of a chlorine com- pound, e.g. chloroform, it causes no precipitation of AgCl. Nevertheless, the halogen is in most cases readily exchangeable for other elements or groups, a circumstance of the utmost importance for many organic reactions. This is especially true for the iodine and .bromine compounds, which react more readily than the chlorides, and, on account of their lesser volatility, are easier to work with; thus C 2 ILBr reacts with AgN0 3 at the boiling temperature, and C 2 H 5 I in the cold even. In all these halogen compounds the halogen can be again replaced by hydrogen by inverse substitution, e.g. by sodium amalgam, by zinc dust and hydrochloric or acetic acid, or by heating with hydriodic acid. (See p. 33.) Of fluorine compounds, only a few are known as yet; CH 3 F and C 2 H 5 F are gases. Nomenclature. The best system of nomenclature is to regard them as derived from the corresponding hydrocarbons, e.g. CHClg trichloro-methane, CH 3 I mono-iodo-methane, and if necessary to indicate the carbon atoms to which the halogen radicals are attached, e.g. CH 2 C1CH 2 C1 1 : 2-dichloro-ethane, CH 3 .CHBr 2 l:l-dibromo-ethane, CH 2 Br.CH 2 .CH 2 Br l:3-di- bromo-propane, CH 3 . CH(CH 3 ) . CHBr . CH 2 CH 2 Br 2-methyl- 3 : 5-dibromo-pentane. The following are some of the most important methods em- ployed for the preparation of these halogen derivatives : - 1. By Substitution. Chlorination and Bromination. Chlorine and bromine act for the most part as direct substituents (see p. 31) With the gaseous hydrocarbons their action even in the cold is an extremely energetic one (e.g. chlorine mixed with methane easily causes an explosion, so that dilution with C0 2 is necessary); the higher members require to be heated. 56 II. HALOID SUBSTITUTION PRODUCTS HALOGEN SUBSTITUTION PKODUCTS Saturated Compounds (a) Mono-substituted Derivatives. Chloride. B.-p. -237 + 12-2 46-5 365 78 Sp. gr. 0-952 0-918 0-912 0-882 0-907 Bromide. Iodide. Siy] Ethyl w-Propyl iso-Propyl Prim. n-Butyl (b) Di-substituted Derivatives. Chloride. B.-p. Sp. gr. Methylene... 42 1-337 Ethylene 84 T260 Ethylidene... 58* M89 (c) Tri-substituted Derivatives. Chloroform. CHX 3 b.-p. 61 B.-p. +4-5 38-4 71 60 101 Sp. gr. 1-732 1-468 1-383 1-340 1-305 B.-p. +45 72-3 102-5 89 130 Sp.gr 2-293 1-944 1-786 1-744 1-643 Bromide. B.-p. Sp. gr. 97 2-498 131 2-189 110 2-080 Iodide. B.-p. Sp. gr. 180 3-292 solid; m.-p. 81-82 r 178 2-84 Bromoform. lodoform. b.-p. 151 melts at H9 C sublimes (d} Tetra-substituted Derivative. Chloride. Bromide. CX 4 76 solid; m.-p. 92; b.-p. 189 Carbon tetra- Unsaturated Compounds Chloride. Vinyl, CH 2 :CHX -18 Allyl, CH 2 :CH.CH 2 X 46 Bromide. Iodide. +23 56 70 101 Trichlorethylene boils at 88, tetrachlorethylene at 121. Monochlor- and monobrom-acetylene are gaseous. Compounds of the type CCl 3 Br, CCl 2 Br 2 , CC1 2 I 2 , &c., arc also known. The first halogen atom enters most easily into the com- pound, the substitution becoming more difficult as the number of those atoms present increases. In the case of the higher hydrocarbons there usually result two isomeric mono-substi- tution products. The action of the halogens is further facili- tated by sunlight, and by the presence of iodine, this latter acting as a carrier of chlorine by the alternate formation of IC1 3 and IC1, thus: IC1 3 = IC1 + 2 Cl. Antimony penta- FORMATION OF HALOGEN DERIVATIVES 57 chloride and ferric chloride act in the same way (and also for brominating and iodating, B. 18, 2017; A. 231, 195); iron wire is especially useful in brominating (B. 24, 4249). When complete chlorination is required, the substance in question is repeatedly saturated with chlorine in presence of iodine, and heated in a tube to a high temperature. From methane are formed the whole series of substitution products up to CC1 4 . Ethane first yields ethyl chloride, C 2 H 5 C1, then ethylidene chloride, C 2 H 4 C1 2 , and so on up to C 2 C1 6 . From propane is first produced normal propyl chloride, 3 H 7 C1, and finally C 3 C1 8 . The latter decomposes, upon vigorous chlorination, first into C 2 C1 6 and CC1 4 , and the perchloro-ethane subsequently into two molecules CC1 4 . On chlorinating butane and the higher hydrocarbons strongly, an analogous splitting up of the molecule is effected. Strong chlorination or bromination readily gives rise at the same time to hexachloro- or hexabromo-benzene. Iodine seldom acts as a direct substituent, since by this reaction hydrogen iodide would be formed, which would then reduce the iodine compound back to the hydrocarbon. (See p. 33.) To induce the action, therefore, the HI formed must be removed by HI0 3 or HgO. The iodine substitution products of the hydrocarbons are usually prepared indirectly (according to 2 or 3). 2. From Unsaturated Hydrocarbons. These combine readily with halogen or halogen hydride. (See p. 44.) Ethylene gives with hydrochloric, hydrobromic, and hydri- odic acids, ethyl chloride, &c., i.e. mono-substitution products of ethane; with chlorine, &c., it gives di-substitution products. The compound C 2 H 4 C1 2 , obtained by the action of chlorine, is called ethylene chloride, has the constitutional formula CH 2 C1.CH 2 C1, and is isomeric with the ethylidene chloride CH 3 .CHC1 2 , obtained by the chlorination of C 2 H 5 C1. (For an explanation of this isomerism, see p. 62.) Propylene combines with hydriodic acid to isopropyl iodide, C 3 H 7 I, which is reconverted into propylene by elimination of HI. But the same propylene results from a compound isomeric with isopropyl iodide, viz. normal propyl iodide (and also, of course, from the above-mentioned normal propyl chloride), by the elimination of hydrogen iodide (or chloride), so that by this reaction normal propyl iodide can be transformed into iso- propyl iodide. (See p. 60.) From the three butylenes there 58 II. HALOID SUBSTITUTION PRODUCTS are formed two butyl iodides, viz. secondary and tertiary, which, as well as the two other existing butyl iodides, yield these butylenes again with alcoholic potash; in this way the two last-mentioned butyl iodides are convertible into their isomers, the two first (see p. 61). A study of the constitution of the compounds formed, shows that in these additive reactions the halogen invariably attaches itself to that carbon atom with which are combined the least number of hydrogen atoms, e.g. CH 3 CH : CH 2 -f HI = CH 3 CHI CH 3 (not CH 3 CH 2 CH 2 I) ; from C 3 H 7 X onwards, therefore, we obtain only " secondary " and " tertiary " * compounds. 3. From Compounds containing oxygen. (a) From the alcohols C^H^OH. In these the OH is readily exchangeable for chlorine, bromine, or iodine by the action of halogen hydride, thus: C 2 H 6 OH + HBr ^ C 2 H 6 Br + H 2 0. In such exchange the halogen takes the place of the hy- droxyl, so that the constitution of the haloid product corre- sponds with that of the alcohol used. These reactions are reversible or balanced, and a state of equilibrium is reached; according to the law of mass action, it is therefore necessary either to use a large excess of halogen hydride (e.g. to saturate with the gas or to heat in a sealed tube), or to remove the water formed, by sulphuric acid, zinc chloride, &c. Methyl and ethyl chlorides are easily prepared by distilling the corresponding alcohol with common salt and sulphuric acid, or by leading hydrochloric -acid gas into the warmed alcohol containing half its weight of zinc chloride in solution (Groves). The chlorides of phosphorus are also applicable for the sub- stitution of OH by Cl, since they react in the same way with alcohols as with water, thus : POL + 3 HOH = P(OH) 3 4- 3 HC1 PC1 3 4- 3C 2 H 6 OH = P(OH) 3 4- 3C 2 H 6 C1. * The names "primary", "secondary", and "tertiary" compounds are founded upon those of the alcohols primary, secondary, and tertiary ir question, from which they can be prepared according to method 3, a. MONO-SUBSTITUTION PRODUCTS 59 Phosphorus pentachloride is most frequently used for this purpose, PC1 6 H- C 2 H 6 OH = C 2 H 6 C1 + HC1 + POC1 3 . Phosphorus oxychloride itself is also sometimes employed. Of especial importance here is the application of the halogen compounds of phosphorus in the production of bromine and iodine compounds. The former need not be prepared before band, the end being achieved by gradually bringing phosphorus and iodine or bromine together in presence of the alcohol: 3CH 3 OH + P + 31 = 3CH 3 I This is the method usually employed for the preparation of methyl and ethyl iodides. (b) The halogen -derivatives may also be prepared from polyhydric alcohols, e.g. trichlorhydrin, C 3 H 6 C1 3 , from gly- serol, C 3 H 5 (OH) 3 , and PC1 5 ; isopropyl iodide, C 3 H 7 I, or allyl iodide, C 3 H 5 I, from glycerol and PI 3 according to the con- ditions of the experiment (see p. 60); hexyl iodide, C 6 H 13 I, f rom mannitol, C 6 H 8 (OH) 6 and HI, the latter acting here as t reducing agent also. (c) From aldehydes and ketones (see these), dichloro-sub- stitution products are formed by the action of PC1 5 , e.g. ethyli- lene chloride, CH 3 .CHC1 2 , from aldehyde, CH 3 .CH:0; ace- tone chloride, CH 3 CC1 2 CH 3 , from acetone CH 3 -CO-CH 3 . 4. Chlorine and bromine compounds are frequently formed Tom the corresponding iodine or bromine ones by direct ex- change, e.g. isopropyl bromide from the iodide, or methylene >romide from methylene iodide ; (also by treatment with mer- curic chloride, stannic chloride, or fuming hydrochloric acid). Conversely the chlorides and bromides may be transformed nto the iodides by heating with sodium iodide in alcoholic jr acetone solution (B. 18, 519), dry calcium iodide (B. 16, 392), or with fuming hydriodic acid. MONO-SUBSTITUTION PKODUCTS The methyl and ethyl compounds are usually obtained from fche corresponding alcohols by one or other of the following methods: (a) Grove's method (p. 58); (b) action of concen- trated sulphuric acid and sodium halide; (c) phosphorus and halogen. Methyl chloride is often obtained by heating trimethy- lamine hydrochloride at 360. (For physical properties, see 60 II. HALOID SUBSTITUTION PRODUCTS Table.) Methyl chloride is used for the production of artificiE cold, for extracting perfumes from flowers, and for methylal ing dyes in the colour industry. It burns with a greer bordered flame. Ethyl Fluoride, C 2 H 5 F. A gas of ethereal odour, whic liquefies at 48; it burns with a blue flame, and does no attack glass. Each Propyl halide, C 3 H 7 X, exists in two isomeric form* the normal propyl and the isopropyl compounds, the forme boiling at a somewhat higher temperature than the latter. T the normal compounds the constitutional formula CH 3 'CH 2 CH 2 X is ascribed, and to the iso-compounds the formul CH 3 CHX'CH 3 , since they are derivable respectively fror normal propyl alcohol and from isopropyl alcohol or acetone the constitutions of which can readily be determined. According to theory only these two cases are possible, sine propane, CH 3 CH 2 'CH 3 , contains but two types of hydroge atoms, viz.: (1) six combined with the end carbon atoms, an< (2) two combined with the middle ones. For the transform* tion of the normal into the iso-compounds, see p. 57. Isopropyl iodide, 2-iodopropane, is prepared from glycero phosphorus, iodine, and water (see p. 59); allyl iodide (p. 65 is formed as intermediate product, and at the same time som propylene (p. 48): C 3 H 6 (OH) 3 + SHI - 3H 2 = C 3 H 6 I 3 = C 3 H 6 I + I 2 . C 3 H 6 I + HI = C 3 H 6 + I 2 . C 3 H 6 I -f 2 HI = C 3 H 7 I + I 2 . Each Butyl-haloid compound, C 4 H 9 X, is known in for isomeric forms, which differ from one another in boiling-poir (up to 30). Four isomers are theoretically possible; thus from norm? butane, CH 3 -CH 2 .CH 2 .CH 3 , are derived: (a) CH 3 .CH 2 .CH 2 .CH 2 I and (b) CH 3 .CH 2 .CHI.CH 3 Normal butyl iodide (I-iodobutane) Secondary butyl iodide (2-iodobutane according to whether a " terminal " or " central " hydroge atom is replaced; similarly from trimethylmethane, CH(CH 3 ) are derived: (c) 3>CH.CH 2 I and (d) ]|j>CI.CH 3 Is'obutyl iodide Tertiary butyl iodide (Z-methyl-B-iodopropane) (Z-methyl-Z-iodopropane). The constitutions of these four compounds follow fror Y DI-SUBSTITUTION PRODUCTS 61 hose of the four corresponding butyl alcohols (p. 67), from hich they can be prepared by the action of halogen hydride. For transformations, see p. 58. Isobutyl bromide changes nto the tertiary compound when heated at 230-240, prob- bly owing to the intermediate formation of butylene. The Isobutyl compounds are the easiest to prepare (from sobutyl alcohol). The Tertiary readily react with H 2 to orm the alcohol and halogen hydride, this taking place even n the cold in the case of the iodide. These mono-halogen derivatives are one of the most impor- ant groups of reagents employed by the organic chemist, on ccount of the readiness with which the halogen atoms may >e replaced by other radicals. ome of the more characteristic reactions are: I. Eeplacement of halogen by hydrogen. Inverse substi- , 1C ution (see p. 33). , e 2. Eeplacsment of halogen by OH (hydroxyl) (p. 71), C 2 H 5 I + H 2 = C 2 H 6 OH + HI, generally by the aid of aqueous alkali, moist silver oxide, or ead oxide and water. 3. Alkalis in alcoholic solution, or alcoholic solutions of odium methoxide (CH 3 ONa) or sodium ethoxide (C 2 H 5 ONa), is a rule, eliminate halogen hydracids, and yield olefines, 3H 2 ICH 3 HI = CH 2 :CH 2 . For the reaction it is neces- ary that the halogen derivative contain at least two carbon atoms, and that a hydrogen atom should be attached to a car- )on atom adjacent to the one to which the halogen is united. 4. The halogen may be replaced by the amino group .NH 2 by the aid of ammonia under pressure, by the nitro group or nitrite radical .0N:0 (p. 94), and by the nitrile radical .C|N (p. 100). For their use as synthetical reagents, see pp. 121, 228, 237. DI-SUBSTITUTION PRODUCTS Methylene chloride, CH 2 C1 2 , Methylene bromide, CH 2 Br 2 , ind Methylene iodide, CH 2 I 2 , are colourless liquids which ire obtained either from the tri-haloid substitution products Dy inverse substitution, or from the mono-substitution pro- lucts by the introduction of more halogen. (See table, 56.) 62 II. HALOID SUBSTITUTION PRODUCTS The compounds C 2 H 4 X 2 are known in two isomeric forms, to which are assigned the constitutional formulae: CH 2 X-CH 2 X (ethylene) and CH 3 -CHX 2 (ethylidene). The former result from the addition of halogen to ethylene, or from the action of halogen hydride or phosphorus haloids upon glycol, C 2 H 4 (OH) 2 (see this), e.g. ethylene bromide, by passing ethylene into bromine and water at the ordinary temperature. The ethylene compounds yield acetylene with alcoholic potash, or better, alcoholic solution of sodium ethoxide, and are transformed into glycol by exchanging their halogen atoms for hydroxyl under the influence of potassium carbonate solu- tion. Glycol, CH 2 (OH).CH 2 .OH, with hydrochloric acid yields glycol mono-chlorhydrin, CH 2 C1 CH 2 OH, and this on oxidation yields mono-chloracetic acid, CH 2 C1-COOH. In this acid it can be shown that the chlorine and hydroxyl radicals are attached to distinct carbon atoms; hence in glycol the two hydroxyl groups, and in ethylene dibromide the two bromine atoms, are almost certainly united to distinct and not to the same carbon atoms. The Ethylidene compounds are obtained from aldehyde (para-aldehyde) by exchange of the oxygen for halogen by means of phosphorus chloride, &c. Ethylidene chloride, also called ethidene chloride, or 1:1- dichloroethane, is, however, most conveniently prepared with phosgene, COC1 2 , thus: CH 3 .C<J + COC1 2 = C It is also formed by the further chlorination of CgHgCl, and is a by-product in the manufacture of chloral. Its boiling-point (57) is lower than that of ethylene chloride (84). It is an anaesthetic. Propylene chlorides, C 3 H 6 C1 2 , bromides and iodides, are likewise known. One group is formed by the addition of halogen to propylene, and thus has an unsymmetrical con- stitution, e.g. propylene chloride, 1:2- dichloropropane, CH 3 CHC1 CHgCl. Isomeric .with this group are the sym- metrically-constituted Trimethylene derivatives, of which tri- methylene-bromide, 1 : 3-dibrorno-propane, CH 2 Br CH 2 CH 2 Br, results from the addition of hydrobromic acid^to allyl bromide ; = CH 2 Br.CH 2 .CH 2 Br. CHLOROFORM, ETC. 63 TRI-SUBSTITUTION PRODUCTS Chloroform, CHC1 3 (Liebig and Soubeiran, 1831; formula established by Dumas, 1835). Fwmation. 1. From methane and methyl chloride (see p. 57). 2. By heating alcohol, or even better, acetone, with bleaching -powder and water. When alcohol is used, the bleaching-powder probably first oxidizes it to aldehyde, then chlorinates to chloral, and ultimately hydrolyses (see below) to chloroform. 3. Together with alkali formate by warming chloral or chloral hydrate with aqueous alkali: CCl 3 .CHO + NaOH = CHC1 3 + HC0 2 Na. This last method of formation is the best for the preparation of pure chloroform. It is a colourless liquid of a peculiar ethereal odour and sweetish taste, is sparingly soluble in water, and solidifies below -70. B.-pt. 61-2. Sp. gr. 1-527. It dissolves fats, resins, caoutchouc, iodine, &c., and is also a most valuable anaesthetic (Simpson, Edinburgh, 1848). The carbylamine reaction (see Iso-nitriles) furnishes a deli- cate test for the presence of chloroform. Bromoform, CHBr 3 , is sometimes present in commercial bromine. lodoform, CHI 3 (Serullas, 1822; formula established by Dumas), is prepared by warming alcohol with iodine and ulkali or alkaline carbonate: C 2 H 5 OH + 4 1 2 + 6 KOH = CHI 3 + HCO 2 K + 5 KI + 5 H 2 O. It can also be prepared in the same way from acetone, aldehyde, lactic acid, and, generally, from compounds which "contain the group CH 3 CH(OH) - C, or GHg-GQ-G (Ueben). An electrolytic method consists in passing an electric current through a solution containing potassium iodide, sodium car- bonate, and alcohol, the temperature being kept at 65. Some 85 per cent of the potassium iodide is thus converted into iodoform. It crystallizes in yellow hexagonal plates, melts at 119, has a peculiar odour, is volatile with steam, and is an^ important antiseptic. It contains only 0'25 per cent H, which at first caused the presence of the latter to be overlooked. Methyl chloroform, CH 3 -CC1 3 . This compound, the tri- chloride of acetic acid, also acts as an anaesthetic. 64 II. HALOID SUBSTITUTION PRODUCTS Glyceryl chloride, Trichlorhydrin, l:2:3-trichloropropane, CHgCl-CHCl-CHjCl, is obtained from glycerol and PC1 5 (p. 59). B.-pt. 158. The corresponding bromine compound is also known, but not the iodine one, C 3 H 5 I 3 , which decom- poses in the nascent state (i.e. when glycerine, phosphorus, and iodine react together) into allyl iodide, C 3 H 5 I, and I 2 . HIGHER SUBSTITUTION PRODUCTS Carbon tetrachloride, CC1 4 . Can be prepared from chloro- form or carbon disulphide and chlorine. It is a colourless liquid, boils at 77, and is used as a solvent for fats, &c. Perchloro-ethane, C 2 CI 6 . Ehombic plates of camphor-like odour. Melts and sublimes at 185. The chemical properties of these polyhalogen derivatives are somewhat similar to those of the monohalogen derivatives. They may be reduced, transformed into the corresponding alcohols, or the halogen atoms replaced by NH 2 radicals, &c. The action of alkalis on the polyhalogen derivatives, in which the halogen atoms are attached to the same carbon atom, OTT is interesting, e.g. CH 2 C1 2 gives not CH 2 <^QTT, but CH 2 :0 formaldehyde and H 2 0; CHC1 3 gives not CH(OH) 3 , but this compound water, viz. 0:CHOH, formic acid. Similarly, C01 4 gives not C(OH) 4 , but C0 2 + 2H 2 0, and CH 3 .CHBr 2 gives CH 3 .CH(OH) 2 - H 2 0, i.e. CH 3 .CHO. Many of these reactions require high temperatures; the substances must be heated with the alkali in sealed tubes under pressure. It is characteristic of carbon derivatives that compounds which contain two or more hydroxyl radicals attached to the same carbon atom are unstable, and, as a rule, immediately eliminate water yielding an aldehyde, acid, &c. Ammonia and chloroform at a red heat yield HCN and HC1. B. Haloid Derivatives of the Unsaturated Hydrocarbons These compounds are obtained either by partially withdraw- ing halogen or halogen hydride from the halogen derivatives of the saturated hydrocarbons, or by incompletely saturating the hydrocarbons poorer in hydrogen with halogen or halogen hydride, e.g. : C 2 H 4 Br 2 - HBr = C 2 H 3 Br. C 2 H 2 -f HBr = C ? H 3 Br. III. MONOHYDRIC ALCOHOLS 65 The allyl compounds, C 3 H 5 X, are obtained from ailyl alcohol and halogen hydride or phosphorus haloids. These unsaturated products are very similar to the corre- sponding saturated ones, but they are, of course, capable of combining further with halogen or halogen hydride, and they exist in stereo-isomeric modifications. (See Fumaric Acid.) In the unsaturated compounds the halogen atoms are, as a rule, not so readily replaced by other radicals, e.g. OH, NH 2 , as in the saturated halogen derivatives. The following may be mentioned : Vinyl bromide, bromo-ethylene, CH 2 :CHBr; is usually pre- pared from ethylene di-bromide and alkali. Allyl -chloride, -bromide, and -iodide, 3-iodo-l-propene, CH 2 :CH.CH 2 X. These are of importance on account of their relation to the allyl compounds found in nature, e.g. oil of mustard and oil of garlic. The iodide is prepared from glycerol, phosphorus, and iodine, and from it, by means of HgCl 2 , the chloride. Isomeric with these are the propylene compounds, e.g. a-chloro-propylene (I-chloro-l-propene), CHC1:CHCH 3 . III. MONOHYDRIC ALCOHOLS, OR ALKYL HYDROXIDES Alcohols may be regarded as paraffins in the molecules of which one or more hydrogen atoms have been replaced by one or more monovalent hydroxyl groups, H. The H group is thus characteristic of alcohols. For the proof of the presence of the OH group, see p. 17. They are usually divided into groups, according to the number of such radicals contained in the molecule: d%dnc,e.g.C 2 H 4 (OH) 2 ; trihydric, e.g. C 3 H 5 (OH) 3 ; hemhydric, e.g. C 6 H 8 (OH) , &c. The monohydric alcohols are either saturated or unsaturated, according to the hydrocarbons from which they are derived. The unsaturated closely resemble the saturated, except that they are capable of forming additive compounds. (B480) 66 III. MONOHYDRIC ALCOHOLS A. Monohydrie Saturated Alcohols, C n H to+1 OH (See Table, p. 67.) The lowest members of this series are colourless mobile liquids, the middle ones are more oily, and the highest from dodecyl alcohol, C 12 H 25 OH, onwards are solid at the ordi- nary temperature, and like paraffin in appearance. Gaseous alcohols are unknown; and it is thus obvious that the intro- duction of OH for H raises the boiling-point of a substance. Compare B.-p. B.-p. CH 4 -164 CH 3 OH 66 CH, -93 C 9 H 5 OH 78 C! 2 H 6 (OH) 78 C;H 4 (OH) 2 197 With compounds of analogous constitution the boiling- point rises with tolerable regularity; in the case of the lower members by about 19, and higher up in the series by a smaller number. The lowest members are miscible with water, but this solubility rapidly diminishes as the molecular weight in- creases; thus butyl alcohol requires 12 parts, and amyl alco- hol 40 parts of water for solution, while the higher members are no longer soluble in water. The former can be separated or "salted out" from their aqueous solution by the addition of salts, e.g. K 2 C0 3 and Ca01 2 . The specific gravity is always < 1. The highest members (over C 16 ) can be distilled undecomposed only in a vacuum; at the ordinary pressure they break up into olefine and water. The lowest members possess a spirituous odour, those with more than five C atoms an odour of fusel, and both have a burning taste, while the highest members are like paraffin in appearance and without either taste or smell. CONSTITUTION AND ISOMERS; CLASSIFICATION OF THE ALCOHOLS Propyl alcohol, C 3 H 7 OH, and the higher members exist in different isomeric modifications; thus there are two propyl, four butyl, and eight amyl alcohols, &c. The number of isomeric forms theoretically possible can be determined by taking the formulae for the corresponding satu- rated hydrocarbons, and seeing in how many different positions MONOHYDRIC SATURATED ALCOHOLS 67 tqoooooqooccco6qooooo ;-> : i ! : : : I I Si O O b O 00 00 00 ooooooooooo ss sssssss * O5 O O 00 i i 00 1^ 00 66 6 oo !> 66 w M9 oo W"W M oo ?'?'?'? ^ - CC W O C3 C fl ^H^-ftft i 22 PL(Pk 1 1 i i i W i !JH II !1K a ;-p 68 III. MONOHYDRIC ALCOHOLS the OH group can be introduced, e.g. CH 3 CH 2 CH 3 , propane, can obviously give CH 3 .CH 2 .CH 2 .OH and CH 3 .CH(OH).CH,, two distinct propyl alcohols. Butane exists in two forms : CH 3 CH 2 CH 2 CH 3 or normal and (CH 3 ) 3 CH or iso. From the n we can get CH 3 .CH 2 .CH 2 .CH 2 .OH and CH 3 .CH 2 .CH(OH)-CH 3 ; from the iso (CH 3 ) 2 CH CH 2 OH and (CH 3 ) 3 C OH; but no more. Of these isomerides, some only are oxidizable to acids, C n H 2n O 2 , containing an equal number of carbon atoms, an aldehyde, C n H 2n O, being formed as intermediate product. Such alcohols are termed primary alcohols (primary propyl, butyl, and isobutyl alcohols, &c.). Another class of alcohols is not oxidizable to acids with an equal number of atoms of carbon, but to ketones, C n H 2n O, by the removal of 2 atoms of hydrogen, e.g. isopropyl alcohol yields acetone, C 3 H 6 0. These are termed secondary (secon- dary butyl alcohol). Upon further oxidation the ketones do indeed yield acids, which, however, contain not an equal but always a smaller number of carbon atoms, the carbon chain having thus been broken up. Lastly, the third class of alcohols, the tertiary, yield upon oxidation neither aldehydes, ketones, nor acids with an equal number of carbon atoms, but only ketones or acids containing fewer atoms of carbon. Constitution of the Alcohols. In the molecule of a mono- hydric alcohol one of the hydrogen atoms plays a part different from that of the others; thus it is replaceable by metals (K and Na), and by acid radicals, and, together with the oxygen atom, combines with the hydrogen of a halogen hydride to form water, while the other hydrogen atoms of the alcohol remain unchanged. This hydrogen atom, which has already been formulated under the Theory of Types apart from the others, is called the "typical" or "extra-radical" hydrogen atom. It is not joined directly to the carbon atom, but through the oxygen one, a conclusion which is confirmed by CONSTITUTION OF MONOHYDRIO ALCOHOLS 69 the formation of alcohols by the action of alkalis (KOH) on monohalogen derivatives of the paraffins. (See p. 71.) This point has been previously discussed (p. 17) for ethyl alcohol. The alcohols therefore contain a hydroxyl group, OH, and their general constitutional formula is (C n H 2n+1 ) OH. According to theory, this hydroxyl can either replace an atom of hydrogen in a methyl group, in which case an alcohol containing the group CH 2 OH (one carbon atom being joined to the other by a single bond) results, e.g. CHg'CHg'OH. Or it can replace the hydrogen of a CH 2 : group in a hydro- carbon, so that the resulting compound contains the group :CH'OH, the carbon being here joined to two other carbon atoms. Or, lastly, it is possible that in a hydrocarbon with a branching carbon chain, the hydrogen of a methine group CH* may be replaced by hydroxyl, when the resulting alcohol would contain the group :COH, in which one carbon atom is joined to three others. TT Now, it is easy to see that the group m G^\r\ 2 ii can ) by further oxidation, be transformed into *G\Q.jj- The latter, which is termed carboxyl, is contained in the acids CJI^O^ or Cn.jHgn^COOH, which are formed by the oxidation of the primary alcohols. Consequently it is the primary alcohols which contain the group CH 2 OH. The group :CH-OH can likewise be changed into :C:0 (i.e. C<Cojj H 2 0\ which is the characteristic group of the ketones, by oxidation. A further introduction of or OH, whereby acids containing the group CO'OH would ensue, is not possible in this case without a rupture of the carbon chain, since the carbon atom is tetravalent. Since then it is the secondary alcohols which upon oxidation yield ketones, and not acids with an equal number of carbon atoms, the group :CH-OH is characteristic of these. Finally, the group jC-OH already contains the maximum of oxygen which can be combined with a carbon atom already linked to 3 other atoms of carbon. A compound, therefore, in which this atomic group is present, cannot yield, when oxi- dized, an aldehyde, acid, or ketone with an equal number of carbon atoms in the molecule, but the result of such oxidation must be the breaking of the carbon chain, and the formation of acids or ketones containing a smaller number of carbon 70 III. MONOHYDRIC ALCOHOLS atoms in the molecule. This being the behaviour of tertiary alcohols, the group iC-OH is peculiar to them. The existence of the three classes of alcohols finds in this \vay a thoroughly satisfactory explanation from theory. The secondary and tertiary alcohols were predicted by Kolbe in 1859 from theoretical considerations (A. 113. 301: 132, 102). Among the isomeric alcohols the primary possess the highest, and the tertiary the lowest boiling-points (cf. p. 67). Similar generalizations appear to hold good for other physical pro- perties, e.g. specific gravity, specific refractive indices, and capillarity constants. The tertiary have the highest melting- points. Determination of Constitution. The determination of the con- stitution of any special alcohol is based largely on its method of formation and on its products of oxidation. E.g. Isopropyl alcohol may be obtained by the reduction of acetone (CH 3 ) 2 C:O, and must therefore have the constitutional formula (CH 3 ) 2 .CH.OH, and not CH 3 .CH 2 -CH 2 .OH. This is con- firmed by the fact that on oxidation it yields the ketone acetone, and must necessarily be a secondary alcohol with the grouping :CH-OH. Similarly isobutyl alcohol must be represented as (CH 3 ) 2 - CHCH 2 'OH, since on oxidation it yields zso-butyric acid, the constitution of which is known to be (CH^-CH-CO-OH. Occurrence. Different alcohols are found in nature combined with organic acids as esters in ethereal oils and waxes; e.g. methyl, ethyl, butyl, hexyl, and octyl alcohols, and also those with 16, 27, and 30 carbon atoms; ethyl alcohol also occurs in the free state. /. General Methods of Formation. 1. By " saponification " or "hydrolysis" of their esters, i.e. by boiling these. with alkalis or mineral acids, or by the action of superheated steam, thus: C 6 H 5 .CO-OC 2 H 6 -f KOH = C C H 5 .(X).OK + C 2 H 6 OH. Ethyl benzoate Potassium benzoate. Some esters, e.g. ethyl hydrogen sulphate, decompose when simply warmed with water: /SO 2 VOH"+H-OH = C 2 H f) .OH + SO 2 (OH) 2 . Most of these processes of hydrolysing require some little time, and the ester is boiled with the alkali (KOH solution) in a flask fitted with a reflux condenser. METHODS OF FORMATION 71 2. From the halogen compounds C n H 2n+1 X, and therefore indirectly from the paraffins and olefines (pp. 55 and 57). In the latter case secondary or tertiary alcohols, from C 3 on, are obtained since the halogen of the haloid compounds becomes attached to that carbon atom to which the smaller number of hydrogen atoms are united. (a) By warming these, especially the iodides, with excess of water to 100; sometimes by simply allowing the mixture to stand (tertiary iodides) : C 2 H 6 };+HX)H = C 2 H 5 .OH-f HI. When but little water is used, a state of equilibrium is reached as the reaction is reversible. These halogen com- pounds may also be termed the esters of the halogen hydracids, so that, strictly speaking, the mode of formation 2 a is in- cluded in 1. (b) Frequently by digesting with moist silver oxide (which acts here like the unknown hydroxide, AgOH), or by boiling with lead oxide and water: OH = C 2 H 6 .OH (c) Upon warming with silver or potassium acetate, the acetate of the alcohol in question is formed, and this is then hydrolysed : C 2 H 5 I + CH, COO Ag = CH 3 - COOC 2 H 6 + Agl CH 3 .COOC 2 H 5 + HOK = C 2 H 6 -OH + CH^COOK. 3. By the fermentation of the carbohydrates (e.g. grape-sugar), the alcohols with 2, 3, 4, 5, and, under certain conditions, even 6 atoms of carbon are produced. (Yeast fermentation.) 4. On treating the primary amines (see these) with nitrous acid: 5. From polyhydric alcohols by replacing several of the hydroxyl groups by halogen atoms, and then reducing the halogen derivative: C 3 H 6 (OH) 3 + 2HC1 = C 3 H 6 C1 2 (OH) + 2H 2 O. Glycerol Dichlor-hydrin. C 3 H 6 (OH)C1 2 + 4H = C 3 H r .OH + 2HC1. Isopropyl alcohol. Secondary alkyl iodides are often obtained by the action 72 III. MONOHYDRIC ALCOHOLS of HI and P on polyhydric alcohols, and these on hydrolysis yield secondary alcohols, e.g.: C 3 H 6 (OH) 3 C 3 H r I C 3 H 7 .OH. Glycerol s-Propyl iodide s-Propyl alcohol. C 4 H 6 (OH) 4 C 4 H 9 I C 4 H 9 .OH. Erythritol s-Butyl iodide s-Butyl alcohol. II. Special Metlwds of Formation. 1. Primary alcohols are obtained from aldehydes by reduction with sodium amalgam and very dilute sulphuric acid (Wurtz); or with acetic acid and zinc dust, when the alkyl acetates are formed : CH 3 .CH:0+2H = CH 3 .CH 2 .OH. This reaction is somewhat similar to the reduction of an olefine to a paraffin. In both cases a double bond is converted into a single bond, and an atom of hydrogen is added on to each atom between which the double bond originally existed. Similarly from acid anhydrides (or esters, but not the free acids) and nascent hydrogen, or by the reduction of the acid chlorides, when an ester of the alcohol is formed by the action of the unreduced chloride on the alcohol. 2. Secondary alcohols are formed by the action of nascent hydrogen (sodium amalgam) on the ke tones, CJS.^0: CH 3 .CO.CH 3 + 2H = CH 3 .CH(OB>CH 3 . Pinacones are obtained here as by-products. (See Ketones.) 3. Secondary alcohols are also formed by the action of aldehydes on dry ethereal solutions of magnesium alkyl halides (p. 120), and treating the product which results with water or dilute acid: CH 3 CH : + CH 3 . Mg I = CH 3 . CH(OMgl) . CH 3 CH 3 CH(OMgl) . CH 3 + H OH = CH 3 CH(OH) - CH 3 + 1 Mg OH. 4. Tertiary alcohols are formed by the action of (a) ketones, (b) acid chlorides, or (c) esters of organic acids, on magnesium alkyl haloids (Grignard, Ann. Chem. Phys. 1901, 24, 433), and decomposing the products with water : (a) o + C 2 H 6 .Mg.Br = (6) CH 3 - CO Cl -f 2 CH 3 Mg I = (CH 3 ) 3 C - O - Mgl + MglCl. (c) CH 3 .C BEHAVIOUR OF THE ALCOHOLS 73 A somewhat similar reaction is that between acid chlorides and zinc alkyl compounds an older and less effective method due to Butleroff. 5. Secondary or tertiary alcohols sometimes ensue by the direct combination of an olefine with water, e.g. tertiary butyl alcohol, (CH 3 ) 3 COH, from isobutylene. This often gives a simple method for converting a primary into a secondary or tertiary alcohol. The Nomenclature of the alcohols, especially of the secondary and tertiary, is based upon a comparison of them with methyl alcohol, also called carbinol. They are looked upon as carbinol, CH 3 -OH, in which the three hydrogen atoms are wholly or partially replaced by alkyl radicals, thus: Tertiary butyl' alcohol, (CH,) 3 C-OH = triraethyl carbinol: Secondary butyl alcohol, CH 3 .CH 2 .CH(OH).CH 3 , = CH(OH)(CH 3 )(C 2 H 6 ), = methyl-ethyl carbinol The systematic name of the alcohols terminates in "ol", As examples: CH 3 CH 2 CH 2 CH 2 OH Butanol . CH(CH 3 ) CH(OH) CH 3 2 : 3-Dimethylpentan-4-ol. Behaviour. 1. The typical hydrogen atom (p. 68) is replace- able by metals, e.g. readily by K or Na, less readily by Ca, Mg, or Al, with formation of alcoholates, EtONa, Mg(OEt) 2 , &c. : 2 C 2 H 6 OH + 2 Na = 2 C 2 H 6 ONa + H 2 . These react with water, giving rise to a state of equilibrium as represented in the equation Et-ONa + H-OH ^ Et-OH + Na-OH. Briihl (B. 1904, 37, 2066) has described a method for pre- paring the compound CH 3 ONa free from water and alcohol. Primary and secondary, but not tertiary, alcohols combine with baryta and lime to alcoholates at 130. Crystalline com- pounds are formed with calcium chloride, so that this salt cannot be used for drying the alcohols; these compounds are decomposed by water. 2. They enter into the composition of many compounds, as " alcohol of crystallization ". (See pp. 75 and 79.) 3. They react with acids both mineral and organic in some- 74 III. MONOHYDRIC ALCOHOLS what the same manner as metallic hydroxides do, yielding '-alkyl salts or esters and water (cf. Esterification) : CH 3 .COOH = CH 3 .COOK + H 2 O, Acetic acid. OOH ^ CH 3 .COOC 2 H 5 + H 2 0. The methyl and ethyl esters derived from certain substituted benzole acids, e.g. paranitrobenzoic acid, N0 2 C 6 H 4 C0 2 H, are solids with definite melting-points, and are sometimes used in identifying small amounts of these alcohols. 4. Dehydrating agents convert them into defines. 5. With halogen hydracids or phosphorus halides, they yield monohalide derivatives of the hydrocarbons (p. 58). 6. For the behaviour of primary, secondary, and tertiary alcohols upon oxidation, see p. 68 et seq. Methyl alcohol is oxidized to carbon dioxide as the primary product (formic acid) is itself readily oxidized. 7. The primary, secondary, and tertiary alcohols can also be distinguished from one another by the behaviour of the nitro compounds, which are formed by the action of silver nitrite on the iodides (cf. Meyer and Jacobson, I, p. 221). 8. Halogens do not substitute but oxidize. 9. Many alcohols when heated with excess of soda lime yield the sodium salts of the corresponding acids. Methyl alcohol, Methanol, Wood Spirit, CH 3 OH, was' dis- covered in wood-tar by Boyle in 1661, and its difference from ordinary alcohol recognized in 1812 by Phillips Taylor. Its -composition was established in 1834 by Dumas and Peligot. It occurs as methyl salicylate in Gaultheria pivcumbens (oil of winter green, Canada), as butyric ester in the unripe seeds of Heradeum giganteum, and as ester of benzoylecgonin in cocain. Formation. 1. By chlorinating methane, CH 4 , and hydro- lysing the resulting methyl chloride (Berthelot}. Methyl iodide may be hydrolysed in a similar manner. 2. By the destructive distillation of wood (beech wood) at about 350. By this distillation there are obtained (a) Gases (CH 4 , C 2 H 6 , C 2 H 4 , C 2 H 2 , C 3 H 6 , C 4 H 8 , CO, C0 2 , H 2 ). (b) An aqueous dis- tillate of " pyroligneous acid", containing methyl alcohol (1-2 per cent), acetic acid (10 per cent), acetone (0-1-0-5 per cent), methyl acetate, allyl alcohol, &c. (c) Wood-tar, containing para- ffins, naphthalene, phenol, guaiacols, &c. (d) Wood charcoal. 3. Also by the dry distillation of vinasse. ETHYL ALCOHOL 75 It is prepared commercially from the crude pyroligneous- acid by repeated distillation after neutralization with lime, and is purified by formation of the CaCl 2 compound, which is a solid, and stable at 100; or, better, by transformation into the oxalic or benzoic ester, both of which are easy to purify and hydrolyse. Properties. It is a colourless liquid, boils at 66, and has a specific gravity about O8. The alcohol of commerce usually contains acetone. It burns with a non-luminous flame, dis- solves fats, oils, &c., and acts as an intoxicant like ethyl alcohol. It also enters into the composition of compounds as "alcohol of crystallization", e.g. BaO + 2CH 4 0; MgCL + 6CH 4 0; CaCl 2 + 4 CH 4 O (six-sided plates). It is readily oxidized to formic aldehyde and formic acid, being also con- verted into the latter when heated with soda-lime. Potassium methoxide, CH 3 OK, is a white crystalline powder, and forms a definite crystalline compound CH 3 OK -f CH 3 OH. The anhydrous alcohol dissolves a small amount of dehy- drated cupric sulphate to a blue -green solution. Distilled over heated zinc dust, it decomposes almost quantitatively into CO + 2 H 2 . Uses. For tar colours (also as CH 3 I and CH 3 C1); as methyl ether in the manufacture of ice; for polishes and var- nishes; as Wiggersheim's preservative liquid; for methylating spirits of wine, &c. Ethyl alcohol, Ethanol, Spirits of Wine, C 2 H 5 OH. Liquids containing spirits of wine have been known from very early times, and their concentration either by distillation or by dehydration with carbonate of potash is also an old art. We read of it as " alcohol " in the sixteenth century. Lavoisier arrived at the qualitative, and de Saussure in 1808 the quanti- tative composition of alcohol. In the vegetable kingdom alcohol is only found occasionally, as ethyl butyrate, but in the animal kingdom it occurs in various forms, e.g. in diabetic urine. It is also present in small quantity in coal-tar, bone oil, wood spirit, and bread, fresh English bread containing 0'3 per cent. Formation. 1. From C 2 H 6 by conversion into C 2 H 5 C1 and hydrolysis of the latter according to modes of formation 1 and 2. 2. Ethylene and concentrated H 2 S0 4 react at 160, yielding ethyl hydrogen sulphate, C 2 H 4 + H 2 S0 4 = C 2 H 5 HS0 4 ; 76 III. MONOHYDRIC ALCOHOLS and this when boiled with water gives ethyl alcohol. (See pp. 44 and 70.) This method was discovered by Faraday, and corroborated in 1855 by Berthelot. 3. By the reduction of acetaldehyde CH 3 .CH:O + 2H = CH 3 .CH 2 -OH. 4. Preparation by the Alcoholic Fermentation of Sugar. Directly from grape and fruit sugars, C 6 H 12 6 , and indirectly from cane- sugar, C^H^Ojp after previous hydrolysis to two molecules of C 6 H 12 6 ; also indirectly from malt-sugar, from starch, &c. Fermentations are peculiarly slow decomposition-processes of organic substances which are accompanied, as a rule, with libera- tion of gas and evolution of heat, and which are induced by micro-organisms, or by complex organic nitrogenous substances (enzymes) of animal or vegetable origin. The alcoholic fer- mentation of sugar, i.e. the fermentation which produces spirit, is caused by the varieties of the genus Saccharomyces, the yeast ferment, which forms small oval microscopic cells, multiplying by gemmation. As plants, these require for their sustenance inorganic salts, e.g. phosphates, potassium salts, and nitrogen in the form of ammonium salts, but, as non-assimilating fungi, no carbon dioxide. In the vinous fermentation 94 to 95 per cent of the sugar breaks up into alcohol and carbon dioxide, C 6 H 12 6 = 2C 2 H 6 + 2C0 2 , with 2-5 to 3-6 per cent glycerol, C 3 H 5 (OH) 3 , and 0'4 to 0*7 per cent succinic acid, C 4 H 6 4 , as invariable by-products. In addition to these, most of the higher homologues of ethyl alcohol are also formed the so-called fusel oil the latter re- sulting largely from the presence of foreign micro-organisms. The chief constituent of fusel oil is fermentation amyl alcohol (isobutyl carbinol), C 5 H n OH, but it has also been proved to contain the two propyl alcohols (chiefly isopropyl), normal, iso, and tertiary butyl alcohols, normal and active amyl alcohols, together with higher homologues and esters. They can be separated by means of their hydrobromic esters. Conditions of Fermentation. Fermentation can only go on between the limits of 3 and 35, the most favourable tempera- ture being between 25 and 30. The solution must not be too concentrated, as the organism cannot live in a solution of alcohol of greater concentration than 14 per cent; the presence of air is not strictly necessaiy, but it has a favouring influence, ALCOHOLIC FERMENTATION 77 Yeast loses its activity upon the addition of any reagents which destroy the cells, also when it is thoroughly dried, when heated to 60, when treated with alcohol, acids, and alkalis; the addition of small quantities of salicylic acid, phenol, corrosive sublimate, &c., also prevents fermentation. For a number of years it was thought that the presence of the living yeast plant, or of some other similar organism, was essential for the production of alcoholic fermentation. The recent work of E. Buchner (B. 1897, 32, 2086, 2372; 1898, 33, 971, 2764) has shown that the fermentation is brought about by an enzyme called Zymase, which is contained in the cell. If the yeast cells are crushed with " Kieselgiihr " (a siliceous earth) and water, so that the cell walls are broken, and the mass then filtered through a Chamberland filter under considerable pressure, an extract is obtained which, although practically free from yeast cells, can yet induce alcoholic fer- mentation. The zymase is relatively unstable and easily de- composed, e.g. when the solution is heated or even kept for some time, but it may be preserved by the addition of certain antiseptic substances, such as chloroform, thymol, &c., which readily kill the yeast plant itself. (Compare Chap. XL VIII.) Buchner's researches indicate that fermentations induced by organized ferments are probably due to certain unorganized ferments (enzymes) contained in the cells of the organism. The following materials are used for the preparation of alcohol or of liquids containing alcohol: (a) Grape-sugar, fruit-sugar, i.e. grapes and other ripe fruits, for wine, &c. (b) Cane or beet sugar and molasses for brandy. Solutions of cane-sugar are fermented by yeast, since ordinary yeast always contains small amounts of an enzyme (invertase), which can hydrolyse cane-sugar to glucose and fructose : C 12 H 22 O n + H 2 = C 6 H 12 6 + C 6 H 12 6 , and these are then directly fermented by the yeast organism, (c) The starch of cereals for beer and corn brandy, and of potatoes for potato brandy. The starch is first converted into malt-sugar and dextrine under the influence of diastase, or into grape-sugar, by boiling with dilute acids, and these sugars are then fermented. The transformation of starch into malt-sugar (maltose) and dextrine is a typical example of fermentation by an enzyme, the special enzyme in this case being diastase, a complex organic nitrogen derivative produced during the germination of the 78 III. MONOHYDRIC ALCOHOLS barley in the process of malting. The transformation of the starch into maltose, &c., is in reality a process of hydrolysis induced by the ferment. The maltose C 12 H 22 O n in its turn is hydrolysed by a second ferment (maltose) to grape-sugar, CpHi 2 6 , which is then transformed into alcohol and carbon dioxide. A wine of medium strength contains 8J to 10 per cent alcohol, port wine 15 per cent, sherry up to 21 per cent, champagne 8 to 9 per cent, and beer an average of 2 to 6 per cent. The different varieties of brandy or spirits obtained by " burning ", i.e. by distilling fermented liquids, contain 30 to 40 per cent alcohol, and cognac even over 50 per cent. Purification of alcohol. It is difficult to separate alcohol completely from water by distillation, since their boiling-points are only 22 apart from one another. Even after repeated rectification the distillates are found to contain water. The same reason applies to the difficulty of separating alcohol from its higher homologues (fusel oil). From an alcohol containing 30 per cent of water the fusel oil can be extracted by chloro- form. On the large scale this separation is excellently effected by the use of dephlegmators or fractionating columns, which are based upon the principle of partial volatilization and partial cooling of the vapours (Adam and JBerard; improved by Savalle, Pistorius, Coffey, and others). In this way an alcohol containing 98 to 99 per cent can be obtained. Aqueous alcohol can be deprived of the greater part of its water by the addition of strongly heated carbonate of potash or anhydrous copper sulphate, or by distillation over quick- lime, and the last portions can be extracted by baryta, or by several additions of metallic calcium and repeated distillation. Alcohol containing water becomes turbid on being mixed with benzene, carbon bisulphide, or liquid paraffin oil, and it gives a white precipitate of Ba(OH) 2 on the addition of a solution of BaO in absolute alcohol, and is capable of restoring the blue colour to anhydrous copper sulphate. Alcohol free from water is termed absolute alcohol. Ordinary absolute alcohol usually contains at least 0*2 per cent of water.' Contraction takes place on mixing alcohol and water together, 53-9 volumes alcohol + 49 -8 volumes water giving, not 103-7, but 100 volumes of the mixture. The percentage pf alcohol in any spirit is determined either from its specific PROPERTIES OF ALCOHOL 79 gravity by reference to a specially -calculated table, or by areometers of particular construction, or by its vapour tension as estimated by Geissler's vaporimeter. Properties. It is a colourless mobile liquid with character- istic spirituous odour; boils at 78 - 3, or at 13 under 21 mm. mercury pressure. Solidifies at 112'3, and has sp. gr. 0*79 at 15. It burns with an almost non- luminous flame, is exceedingly hygroscopic, and miscible with water and with ether in all proportions. Forms several cryo-hydrates with water ( + 12Aq., + 3Aq., -j-JAq.). Is an excellent solvent for many organic substances such as resins and oils, and also dissolves sulphur, phosphorus, &c., to some extent. With concentrated sulphuric acid it yields, according to the con- ditions, ethyl hydrogen sulphate, ether, or ethylene. It dif- fuses through porous membranes into a dry atmosphere more slowly than water, and coagulates albumen, being therefore used for preserving anatomical preparations. It is very readily oxidized by the oxygen of the air, either in presence of finely-divided platinum or in dilute solutions in presence of certain ferments, first to aldehyde and then to acetic acid; thus, beer and wine become sour, but not the pure alcohol itself. K 2 O 2 O r or Mn0 2 + H 2 S0 4 oxidize it in the first instance to aldehyde; fuming nitric acid attacks it with explosive violence, yielding numerous products; but, by the action of colourless concentrated HN0 3 , ethyl nitrate can be obtained under suitable conditions; in dilute solution glycollic acid is formed. Alkalis also induce a gradual oxidation in the air; thus, alcoholic potash or soda solutions quickly become brown with formation of aldehyde resin, this latter resulting from the action of the alkali upon the alde- hyde first produced. Alcoholic potash therefore frequently acts as a reducing agent, e.g. upon aromatic nitro-compounds. (See these.) Chlorine and bromine first oxidize alcohol to aldehyde and then act as substituents. (See Chloral.) Chlorinated alcohols can therefore only be prepared indirectly (cf. Ethylene chlorhydrin). When the vapour of alcohol is led through a red-hot tube, H, CH 4 , C 2 H 4 , C 2 H 2 , CgHg, C 10 H 8 , CO, C 2 H 4 0, C 2 H 4 2 , &c., are formed. Of the compounds containing alcohol of crystallization may be mentioned, KOH + 2 C 2 H 6 0, LiCl + 4 C 2 H 6 0, CaCl 2 + 4C 2 H 6 0, and MgCl 2 + 6C 2 H 6 O. Sodium ethoxide, C 2 H 5 ONa, is of special importance among the alcoholates. It is formed by the action of sodium upon 80 III. MONOHYDRIC ALCOHOLS absolute alcohol. The crystals of C 2 H 5 -ONa + 2 C 2 H 6 0, at first obtained, lose their alcohol of crystallization at 200 and change into a white powder of C 2 H 5 ONa. (See also Bruhl.) Sodium ethoxide is of especial value for syntheses, and can frequently be employed in alcoholic solution. This compound is sometimes termed sodium ethylate, but the better name is ethoxide, in order to indicate its close relationship to sodium hydroxide, NaOH. When taken in small quantity alcohol acts as a stimulant, in larger quantity as an intoxicant. Absolute alcohol is poisonous, and quickly causes death when injected into the veins. The presence of considerable amounts of fusel oil has detrimental physiological effects. Detection of Alcohol. 1. By the iodoform reaction* (see lodo- form), when 1 part in 2000 of water can be recognized. 2. By means of benzoyl chloride, CgH 5 COCl, which yields with alcohol the characteristically smelling ethyl benzoate; or of jp-nitrobenzoyl chloride, which yields ethyl ^?-nitrobenzoate melting at 57; the corresponding methyl ester melts at 97. Propyl alcohols, C 3 H 7 OH. 1. Normal propyl alcohol, 1-Propanol, CH 3 . CH 2 . CH 2 OH (Chancel, 1853), is obtained from fusel oil by means of its hydrobromic ester (Fittig), or directly by fractionation. It has also been obtained from propionic aldehyde and propionic anhydride by reduction with sodium amalgam (Rossi). It is a liquid with a pleasant spirituous odour, and boils 19 higher than ethyl alcohol. It is miscible with water in all propor- tions, but may be salted out on addition of calcium chloride. Its constitution follows from that of propionic acid, into which it is converted on oxidation. Of the higher alcohols, w-butyl alcohol, CH 8 .CH 2 .CH 2 . CH 2 'OH, may be obtained from the fusel oil formed when certain special species of yeast (Saccharomyces ellipsoidius) are used in the alcoholic fermentation. Isobutyl carbinol, (CH 3 ) 2 :CH.CH 2 .CH 2 .OH, is the chief constituent of the so-called " fermentation amyl alcohol " obtained by fractional distillation of fusel oil, the other con- stituent being secondary butyl carbinol, C 2 H 6 .CH(CH 3 ).CH 2 .OH. This latter, on account of its action on polarized light, is * Acetaldehyde, acetone, and isopropyl alcohol also givo this reaction, but not methyl alcohol. MONOHYDRIC UNSATURATED ALCOHOLS 81 fenerally known as active (i.e. optically active) amyl alcohol, b is Isevo-rotatory, i.e. rotates the plane of polarization to the left (cf. active valeric acid), and has [a] D 5 '9 at 20. Normal hexadecyl- alcohol, or cetyl alcohol, forms as palmitic ester the chief constituent of spermaceti. The cetyl alcohol of commerce contains, in addition, a homologous alco- hol, C 18 H 38 0. Ceryl alcohol, Cerotin, C 26 H 63 OH, forms as cerotic ester Chinese wax. Melissic, or miricyl alcohol, C 30 H 61 OH or C 31 H 63 OH, is present as palmitic ester in bees'-wax and in Carnauba wax, and is most conveniently prepared from the latter. The alcohols are obtained from all these esters (wax varieties) by hydrolysis with boiling alcoholic potash. B. Monohydrie Unsaturated Alcohols, CnH^OH These are very similar to the saturated alcohols both in physical properties and in general chemical behaviour, but are sharply distinguished from the latter by the formation of addi- tive compounds with hydrogen, halogens, halogen hydracids, &c. 5 e.g.-. CH 2 : CH CH 2 OH + Br 2 = CH 2 Br CHBr CH 2 OH. They thus resemble the olefines owing to the presence of a double bond, and the products are saturated alcohols or their halide derivatives, the latter of which cannot be prepared directly by substitution of the alcohols. These unsaturated alcohols are to be considered as olefines in which an atom of hydrogen is replaced by hydroxyl. According to theory, the existence of alcohols which contain the hydroxy-methylene group, :CH(OH), linked to a Carbon atom by a double bond, might be predicted. To this class belongs" vinyl alcohol (ethenol), CH:CH-OH, which occurs in commercial ether, but which has not yet been isolated (B. 22, 2863), although derivatives of it are known. By the reactions in which one would expect it to be formed, its isomer, CH 3 .CHO (acetaldehyde), is formed; in fact, the grouping :C:CH-OH is usually unstable, passing as it does into the more stable one, :CH-CH:0, a transformation which is most readily explained upon the assumption that water is taken up and again split off. Similarly, instead of the group CH 2 :C(OH).CH 3 , we always get CH 3 .CO.CH 3 . ( B 480 ) 82 III. MONOHYDRIC ALCOHOLS Allyl alcohol (l-Propene-3-ol), CH 2 :CH.CH 2 OH (Cahours and Hofmann, 1856), is present to the extent of O'l to 0'2 per cent in wood spirit, and is formed (1) from allyl iodide; (2) by reduction of its aldehyde, acrolein (see this); (3) by heating glycerol, C 3 H 5 (OH) 3 , with oxalic or formic acid and a little ammonium chloride to 220. The reaction is somewhat similar to the production of formic acid, and in both cases the same product is first formed, viz. glyccryl monoformate CH 2 -OH CH 2 .OH CH 2 .OH CH-OH CH.:OH j CH /"YD" ^\TT ^ITT ' /~\ "/"V^ 'TT* /^ITT V^Jj-2 * vy-CL ^-^-2 * ^ * v/w ; Jtl; V^i2j and this when heated to the required temperature, 220, decomposes into C0 2 , H 2 0, and allyl alcohol. Allyl alcohol is a mobile liquid of suffocating smell, having almost the same boiling-point (97) as rc-propyl alcohol; like the latter, it is miscible with water. It does not take up nascent hydrogen directly, but chlorine, bromine, cyanogen, hypochlorous acid, &c. If cautiously oxidized, it yields glycerol, but stronger 3xidation converts it into its aldehyde., acrolein, and acid, acrylic acid, containing the same number of carbon atoms, and it is therefore a primary alcohol; hence the above con- stitutional formula. C. Monohydrie Unsaturated Alcohols, Cyi^.g.OH These alcohols are derivatives of acetylene and its homo- logues. The compounds possess: (1) The characteristic pro- perties of alcohols. (2) The properties of unsaturated com- pounds. Each molecule of such an alcohol can combine with 1 or 2 molecules of a halogen or halogen hydracid. (3) Most of them possess the further peculiarity of forming explosive compounds with ammoniacal copper and silver solutions, e.g. C 3 H 2 AgOH, the former being coloured yellow and the latter white; acids decompose these compounds into the un- saturated alcohol. Those of them which do not yield such metallic compounds contain, not a triple bond, but two double ones between the carbon atoms. The most important of these alcohols is Propargyl alcohol, OT propinyl alcohol (l-Propin-3-ol) t C 3 H 3 OH, = CH-C-CHsOH, ETHERS 83 a mobile liquid of agreeable odour, lighter than water, and boiling at 114, i.e. somewhat higher than normal propyl alcohol. For further examples of unsaturated alcohols, see Open- chain Terpenes (Chap. XLI, A). IV. DERIVATIVES OF THE ALCOHOLS These may be classed in the following divisions : _ A. Ethers of the alcohols, or alkyl oxides, e.g. C 2 H 5 .0C 2 H 5 , ethyl ether. B. Thio-alcohols and ethers, or alkyl hydrosulphides and sulphides, e.g. C 2 H 5 -SH and (C 2 H 5 ) 2 S. C. Nitrogen bases of the alcohol radicals. D. Other metalloid compounds of the alcohol radicals. E. Metallic compounds of the alcohol radicals, or organo- metallic compounds. A. Ethers Proper (Alkyl- or Alphyl-Oxides) The ethers of the monohydric alcohols are compounds of neutral character derived from the alcohols by elimination of the elements of water (1 molecule water from 2 molecules alcohol). They can frequently be prepared by treating the alcohols with sulphuric acid, and are distinguished from the latter by not reacting with acids to form esters, and by being substituted and not oxidized by the halogens, &c. Only the lowest member of the series is gaseous, most of them are liquid, and the highest are solid. The more volatile ethers are characterized by a peculiar odour which is not shown by the higher members. Constitution. The hydrogen atoms cannot be replaced by sodium or other metallic radicals (see p. 18), and are all presumably attached to carbon. Their structure as alkyl oxides, or anhydrides of mono- hydric alcohols (cf. metallic oxides), follows largely from modes of formation 2 and 3, from the non-reactive character of the hydrogen atoms, and from reactions 4 and 5, p. 85. K;OH C 2 H 5 OH _ C 2 H 5 ^ c 2 H 6 o;n - ^ The alkyl groups contained in them may either be the same, as in ordinary ether and in methyl ether, (CH 3 ) 2 0, in 84 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS which case they are termed "simple ethers"; or they may be different, as in methyl-ethyl ether, CH 3 -0'C 2 H 5 , when they are known as "mixed ethers". Ethers derived from tertiary alcohols are not known. Modes of Formation. 1. By heating the alcohols, C n H 2n+1 OH, with sulphuric acid. The reaction proceeds in two phases, e.g.: (a) C 2 H 5 .OH + OH-S0 2 .OH = OH.S0 2 .OC 2 H 5 + H-OH. (6) OH.S0 2 .OC 2 H 6 +C 2 H 5 .OH = OH.S0 2 .OH In phase a an alkyl hydrogen sulphate is formed, which, when further heated with alcohol, as in b, yields ether and regenerates sulphuric acid. The latter is therefore free to work anew, and in this way to convert a very large quantity of alcohol into ether. This process is theoretically a continuous one, but practi- cally it has its limits, through secondary reactions, such as the formation of S0 2 , &c. A modification of the method consists in heating the alcohol with benzene - sulphonic acid C 6 H 5 S0 2 OH in place of sulphuric acid. No sulphur dioxide is formed, and the reaction becomes in reality continuous. The method is only suitable for primary alcohols; secondary and tertiary under similar conditions yield defines. Hydrochloric, hydrobromic, and hydriodic, among other acids, act similarly tc sulphuric acid; thus ether is obtained when alcohol is heated with dilute hydrochloric acid in a sealed tube to 180, ethyl chloride, C 2 H 5 C1, being formed as an intermediate product When alcohol is heated with hydrochloric acid, a state of equilibrium is established between the alcohol, ether, ethyl chloride, hydrochloric acid, and water, after which the same quantity of each of these products is destroyed as is formed in unit of time. 2. By the action of alkyl halides on sodium -alky late, or also upon alcoholic potash: 3. From alkyl halides and dry silver oxide, Ag 2 (also HgO andNa 2 0): 2C 2 H 6 I Modes of formation 1 and 2 yield mixed as well as simple ethers, e.g.: C 2 H 6 .S0 4 H + CH 3 -OH = C 2 H 5 .O.CH, + H 9 S0 4 . CVE U I + CH 3 ONa = C 6 H U . O CH 3 -f Nal. ETHYL ETHER 85 Properties. 1. The ethers are very stable, e.g. ammonia, alkalis, dilute acids, and metallic sodium have no action upon them, nor has phosphorus pentachloride in the cold. 2. When superheated with water in presence of some acid, such as sulphuric, the ethers take up water and are retrans- formed into alcohols, the secondary more readily than the primary; this change also proceeds, but extremely slowly, at the ordinary temperature. 3. When warmed with concentrated sulphuric acid, alcohol and ethyl hydrogen sulphate are formed : .OH + C 2 H 6 .HS0 4 . 4. When saturated with hydriodic acid gas at 0, the ethers yield alcohol and alkyl iodide : C 2 H 6 .O.C 2 H 5 + HI = C 2 H 6 .OH + C 2 H 6 L When the ethers are " mixed ", the iodine attaches itself to the smaller alkyl group; further interaction yields, of course, two molecules of alkyl iodide. 5. When heated with phosphorus halides the oxygen atom is replaced by two halogen atoms, and two molecules of an alkyl halide are formed. 6. Like the alcohols, the ethers are oxidized by nitric and chromic acids, but halogens substitute in them and do not oxidize; in this latter respect they resemble the hydrocarbons. 7. Many ethers form definite compounds with acids, especially complex acids like H 4 FeC 6 N 6 (B. 190-1, 34, 2688); also with bromine, with metallic salts, &c. (J. C. S. 1904, 85, 1106; Proc. 1904, 165). Ethyl ether, Ethane-oxy-ethane, "Ether" (C 2 H 5 ) 2 0, was dis- covered by Valerius Cordus about 1544, and possibly before that time by Raymond Lully. It was also called " sulphuric ether ", and " vitriol ether ", on account of its being supposed to contain sulphur. Its composition was established by Saus- sure in 1807, and Gay-lMssac in 1815, Preparation. By the continuous process from ethyl alcohol and sulphuric acid at 140, with gradual addition of the alcohol, according to Boullay. It is freed from alcohol by shaking with water, and dried by distillation over lime or calcium chloride, and finally over metallic sodium. Theories of the Formation of Ether. At first the action of the sulphuric acid was considered to consist in an abstraction of water. Later on, it was thought that the acid gave rise to 86 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS a contact action (Mitscherlich, Berzelius), but Liebig showed that this view was incorrect, since ethyl hydrogen sulphate is formed. Liebig assumed that the ethyl hydrogen sulphate decomposed, when heated, into ether and S0 3 ; but Graham, on the other hand, proved that the acid gives no ether when heated alone to 140, but only when heated along with more alcohol. After this, Williamson propounded the theory of etheri- fication at present held, a theory based on the opinion of Laurent and Gerhardt that ether contains two ethyl radicals. Its correctness was proved by mode of formation 2, and also by the preparation of mixed ethers. Properties. It is a mobile liquid with powerful ethereal odour, and is very volatile, even at the ordinary temperature. It melts at -113, boils at + 34'9, has specific gravity = 0'72 at 17 '4, and at 120 has a vapour pressure of 10 atmospheres. It produces considerable lowering of temperature when evapo- rated. It is easily inflammable, and therefore dangerous as a cause of fire, from the dissemination of its very heavy vapour; a mixture of it with oxygen or air is explosive. It is some- what soluble in water (1 part in 10), and, conversely, 3 volumes of water dissolve in 100 volumes of ether; the presence of water can be detected by the milkiness which ensues upon the addition of carbon disulphide. Ether is an excellent solvent or extractive for many organic substances, and also for I 2 , Br 2 , O0 3 , FeCl 3 , AuCl 3 , PtCl 4 , and other chlorides. It forms crystalline compounds with various substances, e.g. the chlorides and bromides of Sn, Al, P, Sb, and Ti, being present in them as " ether of crystallization ". When dropped upon platinum black it takes fire, and when poured into chlorine gas an explosion results, hydrochloric acid being set free. In the dark, however, and in the cold, sub- stitution by chlorine is possible; the final product of the substitution, perchloro- ether, C 4 C1 10 0, is solid and smells strongly like camphor. Ether was first employed as an anaesthetic by Simpson in 1848, but this property had been previously observed by Faraday. It is further used as an extractive in the colour industry, as Hofmann's drops when mixed with 1 to 3 volumes of alcohol, for ice machines, and for the preparation of collo- dion, &c. Methyl ether, (CH 3 ) 2 (Dumas, Peligoi\ closely resembles common ether, is gaseous at the ordinary temperature, but ISOMERISM OF ETHERS 87 liquid under 20, and is prepared on the large scale for the production of artificial cold, Ethyl-cetyl- and dicetyl ethers are solid at the ordinary temperatures. Several ethers with unsaturated alcohol radicals are also known, e.g. allyl ether, (C 3 H 5 ) 2 0, and vinyl -ethyl ether, C2H 3 .O.C 2 H 5 . B.-pt. 35-5. These can combine directly with bromine. Isomers. The general formula of the saturated ethers is CnELjn+aO. Isomerie with each ether is a saturated alcohol, thus C 2 H 6 = methyl ether or ethyl alcohol, C 4 H 10 = di- ethyl ether or butyl alcohol. From C 4 H 10 on, however, several different isomeric ethers are not only possible, but are also known, e.g. di-ethyl ether, (C 2 H 5 ) 2 0, is isomeric with methyl - propyl ether, CH 3 -0'C 3 H 7 ; similarly methyl -amyl ether, CH 3 .O.C 5 H n , ethyl-butyl ether, C 2 H 5 .O.C 4 Hg, and dipropyl-ether, C 3 H 7 0-C 3 H r , are all isomeric. Isomerism of this kind depends upon the fact that the alkyl radicals and hydrogen are homologous, so that if the numbers of carbon atoms are equal, so also must be the numbers of hydrogen. Such isomerism in which the compounds belong to the same class and differ only in the nature of the alkyl group present is termed metamerism. The determination of the constitution of the ethers is based upon (a) their syntheses according to modes of formation 1 or 2, and (b) their decomposition by HI according to Keaction 4. Varieties of Isomerism. The cases of isomerism which have been mentioned up to now are of three kinds. The first was the isomerism of the higher paraffins, which, since it is based upon the dissimilarity of the carbon chains, is often termed cham-isomerism. The isomerism between ethylene and ethyl- idene chlorides or between primary and secondary propyl alcohols depends upon the differences in position of the substi- tuting halogen or hydroxyl in the same carbon chain, and is termed position isomerism. In addition to these there is the third kind, metamerism. Further cases will be spoken of under the Benzene derivatives. B. Thio-aleohols and -ethers The relationship between oxygen and sulphur, indicated by their positions in the periodic classification of the elements, is supported by a study of their carbon derivatives. We have 88 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS a group of sulphur compounds analogous to the monohydric alcohols. These are known as thio-alcohols or " thiols ". Similarly a group corresponding with the ethers is known as the thio- ethers or alkyl sulphides. These are liquids of a most unpleasant and piercing odour, something like that of leeks ; they are nearly insoluble in water, and the lower mem- bers are very volatile. The higher homologues are not so soluble in water, but continue to be soluble in alcohol and ether, and their smell is less strong on account of the rise in the boiling-point. They are readily inflammable. The thio-alcohols, also called mercaptans or alkyl hydro- sulphides, e.g. mercaptan, ethan-thiol, Q 7 H 5 SH, although of neutral reaction, possess the chemical characters of weak acids and are capable of forming salts, the " mercaptides ", especially mercury compounds. The name " mercaptan " is derived from " corpus mercurio aptum ". They are soluble in a strong solu- tion of potash, and their boiling-points are distinctly lower than those of the corresponding alcohols. The thio-ethers, also termed alkyl sulphides, e.g. ethyl sulphide, (C 2 Hg) 2 S, are on the other hand neutral volatile liquids without"acid char- acter. Both classes of compounds are derived from hydrogen sulphide by the replacement of either one or both atoms of hydrogen by alkyl groups, just as alcohol and ether are derived from water: The boiling-points are methyl mercaptan 6, ethyl mercap- tan 36, methyl sulphide 37, ethyl sulphide 92. The constitution of these compounds follows at once from their modes of formation. Formation. The mercaptans may be obtained 1. By warming an alkyl halide or sulphate with potassium hydrosulphide in concentrated alcoholic or aqueous solution : C 2 H 6 Br + KSH = C 2 H 6 .SH + KBr. 2. By heating alcohol with phosphorus pentasulphide, the oxygen being thus replaced by sulphur (KekuU). The thio-ethers are similarly obtained 1. From an alkyl halide or potassium alkyl sulphate and normal potassium sulphide: 2C 2 H 5 .S0 4 K + THIO-ETHERS 89 2. By treating ethers with phosphorus pentasulphide. " Mixed sulphides ", comparable with the " mixed ethers ", can also be prepared,.^. methyl-ethyl sulphide, C 2 H 5 -S.CH 3 . Behaviour. A. The Mercaptans. 1. Sodium and potassium act upon the mercaptans to form sodium and potassium salts, white crystalline compounds, which are decomposed by water. The mercury salts are ob- tained by warming an alcoholic solution of mercaptan with mercuric oxide, e.g. mercuric mercaptide, Hg(C 2 H 5 S) 2 (white plates). With mercuric chloride sparingly soluble double com- pounds are formed, e.g. (C 2 H 5 S)Hg Cl, a white precipitate. The lead salts are yellow-coloured, and are formed when alco- holic solutions of a mercaptan and of lead acetate are mixed. 2. When oxidized with nitric acid the mercaptans are transformed into alkyl-.sulph.onic acids: C 2 H 6 .SH + 30 = fSQ (ethyl-sulphonic acid). 3. The mercaptans in the form of sodium salts are oxidized by iodine or by sulphury! chloride, S0 2 C1 2 (B. 18, 3178), and also frequently in ammoniacal solution in the air to disulphides, e.g. ethyl disulphide, (C 2 H 5 ) 2 S 2 , thus : 2C 2 H 6 S.Na + I 2 = C 2 H 6 .S.S.C 2 H 6 + 2NaI. These are disagreeably-smelling liquids, which have much higher boiling-points than the mercaptans. They are reduced by nascent hydrogen, and with nitric acid yield disulphoxides, e.g. ethyl disulphoxide, (C 2 H 5 ) 2 S 2 2 . B. The Thio-ethers. 1. They yield additive compounds with metallic salts, e.g. (C 2 H 5 ) 2 S, HgCl 2 , which can be crystal- lized from ether. 2. They are capable of combining with halogen or oxygen. Thus ethyl sulphide forms with bromine a dibromide, (C 2 H 5 ) 2 S : Br 2 , crystallizing in yellow octohedra, and with dilute nitric acid, diethyl sulphoxide, (C 2 H 5 ) 2 S:0, a thick liquid soluble in water, which combines further with nitric acid to the compound, (C 2 H 5 ) 2 SO, HN0 3 . Concentrated nitric acid or potassic permanganate oxidizes the sulphides or sulphoxides to sulphones, e.g. ethyl sulphide to (di)-ethyl sulphone, (C.,H 5 ) 2 S0 2 , and methyl-ethyl sulphide to methyl- ethyl sulphone, (CH 3 )(C 2 H 5 )S0 2 . The sulphones are solid well -characterized compounds which boil without decom- position. 90 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS The sulphoxides are reduced by nascent hydrogen to sulphides, but not the sulphones. 3. The behaviour of the sulphides towards the alkyl haloids is of especial interest. Thus the substances (CH 3 ) 2 S and CH 3 I combine even in the cold to the white crystalline triinethyl- sulphine iodide, (CH 8 ) 3 SI, or trimethyl-sulphonium iodide, as it is now generally called in order to emphasize its similarity to the ammonium salts; this is soluble in water, and when heated is resolved into its components. It behaves exactly like a salt of hydriodic acid, and yields with moist silver oxide (but not with alkali) an oily base, trimethyl-sulphonium hydroxide, (CH 3 ) 3 S-OH, which cannot be volatilized without decomposition. This is as strong a base as caustic potash, and resembles the latter so closely that it absorbs carbon dioxide, cauterizes the skin, drives out ammonia, and gives salts with acids even with hydrogen sulphide; these latter closely resemble the alkali sulphides, e.g. they dissolve Sb 2 S 3 (Oefde, 1833; Cahours). The compounds just described are of particular interest with regard to the question of the valency of sulphur. The readiness with which these sulphur compounds are oxidized, and the ease with which they yield additive com- pounds, is undoubtedly due to the readiness with which the S atom passes from the di- to the tetra- or hexa-valent state; for example: ;;;:,, gg>S + Br, gives The sulphoxides are the sulphones \ the sulphonic acids OH /OH or and the sulphonium compounds s C 2 H 6 \ g /'C 2 H 6 ESTERS OF INORGANIC ACIDS 91 Since in ethyl sulphide both the alkyl radicals are bound to the sulphur, this will also be the case in ethyl sulphone, otherwise the sulphones would manifestly be easily saponi- fiable. (See Ethyl-hydrogen sulphite.) The sulphonium hy- droxides also can only be explained very insufficiently as molecular compounds, on the assumption of the divalence of sulphur. The formula (CH 3 ) 2 S + CH 3 OH for trimethyl- sulphine hydroxide does not indicate in the least the strongly basic character of this substance, since it is not explicable why the mere addition of the neutral methyl alcohol to the equally neutral methyl sulphide should produce such an effect. With respect to isomers, the same general conditions prevail in the sulphur as in the corresponding oxygen compounds. SULPHIDES OF UNSATURATED ALCOHOL RADICALS Allyl sulphide, (C 3 H 5 ) 2 S (Wertlieim, 1844), present in the oil of Allium sativum oil of garlic, in Thlasp arvense, &c., may be prepared from allyl iodide and K 2 S (Hofmann, Cahours). B.-pt. 140. Analogous alkyl selenium and tellurium compounds are also known. They are in part distinguished by their exces- sively disagreeable, nauseous, and persistent odour. C. Esters of the Alcohols with Inorganic Acids and their Isomers The esters or alkyl salts may be considered as derived from the acids (see p. 74) by the exchange of the replaceable hy- drogen of the latter for alkyl radicals, just as metallic salts result by exchanging the hydrogen for a metallic radical: KN0 3 . (C 2 H 6 )N0 3 . ethyl chloride. Monobasic acids yield only one kind of ester, "neutral or normal esters", which are analogous to the normal metallic salts of those acids. Dibasic acids yield two series of esters (1) acid esters and (2) neutral esters corresponding respectively with acid and normal salts; thus, C 2 H 6 -HS0 4 and (C 2 H 5 ) 2 :S0 4 are the acid 92 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS and normal ethyl esters of sulphuric acid. Tribasic acids yield three series of esters, &c. The composition of the esters or alkyl salts is therefore exactly analogous to that of metallic salts, so that in the definition of polybasic acids their behaviour in the formation of esters may also be included. The normal esters are mostly liquids of neutral reaction, and often of very agreeable odour, with relatively low boiling- points, and volatilize, eventually in a vacuum, without decom- position. Most of them are very sparingly soluble in water. The acid esters, also called ester-acids, on the other hand, are of acid reaction, without smell, usually very readily soluble in water, much less stable than the neutral esters, and not volatile without decomposition. They act as acids, i.e. form salts and esters. All esters are able to combine with water, and are by this means resolved again into their components, namely, alcohol and acid, e.g. C 2 H 5 NO 3 + H 2 O = C 2 H 6 OH + HN0 3 . This process occurs when the ester is boiled with alkalis or acids, or when heated with steam to over 100, e.g. 150-1SO, and is termed hydrolysis, or saponification, when alkalis are used (see Soaps, p. 158). The reaction is usually conducted in a flask fitted with a reflux condenser, but in a few cases the reaction takes place when the ester is mixed with water at the ordinary temperature. General Modes of Formation. 1. The simplest method for obtaining an ester is by the action of the acid on the alcohol, water always being formed as a by-product. As the reactions are reversible, C 2 H 5 .OH + O:N-OH ^ C 2 H 5 .0-N:0 + H-OH, it is essential that the water formed should be removed from the sphere of action by the aid of concentrated sulphuric acid, fused zinc chloride, &c., or that a large excess of acid should be employed, otherwise after a short time a state of chemical equilibrium is reached, all four compounds are present, and the direct and reverse reactions are proceeding at the same rate; even prolonged heating will then not transform any further amounts of acid and alcohol into ester. Esters are therefore often prepared by adding an excess of ESTERS OF NITRIC ACID 93 concentrated sulphuric acid to a mixture of the alcohol and sodium salt of the acid. 2. The alcohol is heated with the acid chloride, thus : -2C 2 H 6 .OH = 3. The silver salt of the acid is heated with an alkyl iodide; this is a method of very general application, although it often leads to isomers of the expected ester (see also p. 94): CgHs-I + OiN-OAg = O:N-OC 2 H 5 -f Agl. Besides the true esters, there are also included in this division several other classes of acid derivatives isomeric with them, but distinguished from them by not being readily hydrolysed, i.e. by being more stable, e.g. nitre-compounds, sulphonic and phosphinic acids, &c. The hydrocyanic deri- vatives of the alcohols will also be described here for the sake of convenience. These, also, are not hydrolysed in the normal manner into alcohol and acid, but are decomposed in quite a different manner. ESTERS OF NITRIC ACID Methyl nitrate, CH 3 ^0N0 2 , is a colourless liquid, boiling at 66. Ethyl nitrate, C 2 H 5 .0-N0 2 (Millori), is a mobile liquid of agreeable odour and sweet taste, but with a bitter after-taste; it boils at 86, and burns with a white flame. Both esters are soluble in water. The latter is prepared directly from the alcohol and acid, with the addition of urea in order to destroy any nitrous acid as fast as it is formed. Nitric esters contain a large proportion of oxygen in a form in which it is readily given up; they therefore explode when suddenly heated. They are very readily hydrolysed to nitric acid and the alcohol when boiled with alkalis. Tin and hydro- chloric acid reduce them to hydroxylamine : C 2 H 5 .O-N^ + 6H = C 2 H 6 -OH + H 2 N-OH + H 2 O. These two reactions indicate that the nitrogen atom is not directly united to carbon, as it is so readily removed either as nitric acid or as hydroxylamine. 94 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS DERIVATIVES OF NITROUS ACID The compound C 2 H 5 2 N exists in two isomeric forms, repre- sented by the formula C 2 H 5 .0N:0 and C 2 H 5 -N^Q. The former is termed ethyl nitrite, as it is the true ester of nitrous acid, H0N:0; the isomeride is termed nitro-ethane, as it contains the nitro group *N^/^ attached to carbon. a. Alkyl nitrites. These are obtained by the action of nitrous fumes (from arsenious oxide and nitric acid), or of potassium nitrite and sulphuric acid, or of copper and nitric acid upon the alcohols. They are neutral liquids of aromatic odour, with very low boiling-points, and are readily hydrolysed to the corresponding alcohol and acid. When reduced they yield the alcohol, ammonia, and water. Methyl nitrite is a gas; ethyl nitrite boils at 18, has a characteristic odour, and in the impure state, as obtained from alcohol, copper, and nitric acid, is used medicinally under the name of "sweet spirits of nitre". Amyl nitrite, C 5 H n -0N:0, is a pale-yellow liquid boiling at 96, and is used in medicine; it produces expansion of the blood-vessels and relaxation of the contractile muscles. ft. The Nitro-derivatives are colourless liquids of ethereal odour, practically insoluble in water, and boiling at tempera- tures some 100 higher than their isomers. Like the latter they distil without decomposition, and occasionally explode when quickly heated. They are fundamentally distinguished from the alkyl nitrites by not being readily hydrolysed, and by yielding aniino-compounds (see these) on reduction, the nitrogen remaining attached to carbon: -6H = CH 3 .NH 2 + 2H 2 0. Nitro-methane boils at 99-101. Nitro-ethane, C 2 H 5 -N0 9 (V. Meyer and Stub&r, 1872), boils at 113-114, burns with a bright flame, and the vapour does not explode even at a high temperature. Formation. 1. The nitro -compounds may be obtained by treating an alkyl iodide with solid silver nitrite (V. Meyer). When methyl iodide is used nitro-methane alone is formed, with ethyl iodide about equal weights of nitro-ethane and ethyl nitrite, and the higher homologues in regularly decreas- NITRO-DERIVATIVES 95 ing amounts as compared with those of their isomers, from which, however, they may be readily separated by distillation. Tertiary alkyl iodides do not yield mtro-coinpounds : Nitromethane is most readily prepared by the action of sodium nitrite solution on sodium chloroacetate, carbon di- oxide being eliminated, 2. The nitro-derivatives of the lower paraffins cannot be obtained by the direct action of nitric acid on the hydro- carbons, but with some of the higher derivatives this is pos- sible, e.g. heptane, octane, &c. With decane a 30-per-cent yield of a mono-nitro-derivative may be obtained by means of fuming nitric acid. (W&rstall, Am. 1898, 20, 202; 1899, 21, 211; Konowalo/, Abs. 1905, i, 764; 1907, 1, 1.) This method is largely employed in the aromatic series (see Nitrobenzene). The constitution of the nitro-compounds is based on the fact that they are not readily hydrolysed, and that the nitrogen is not removed during reduction, but remains directly bound to carbon in the resulting amines (see these). Consequently the nitrogen of the nitro-compound is directly joined to the alkyl radical i.e. to carbon; for instance: / CH 3 .N< I, or more probably CH 3 -N .N< I X) Nitrogen which is attached directly to an alkyl radical is therefore not removed by hydrolysing agents. Since the nitrogen of the isomeric alkyl nitrites, on the other hand, is easily split off from the alkyl radical either by hydrolysis or by reduction, it is manifestly riot directly combined with the carbon but with the oxygen. The alkyl nitrites, therefore, receive the constitutional formula R-O-NiO, where R repre- sents the alkyl radical. From this follows for the hypothetical hydrated nitrous acid the formula H-O-NrO, and for the anhydride the for- mula (N0) 2 0. The aromatic hydrocarbons, e.g. benzene, C 6 Hg, yield with nitric acid nitro-compounds, thus : C 6 H 6 .H + HN0 3 = C 6 H 6 .N0 2 -f H 2 0. Nitric acid, therefore, contains a nitro- group bound to hydroxyl, corresponding with the formula H0N0 2 . Behaviour. 1. They yield primary amines with acid reduc- ing agents, e.g. iron and acetic acid, tin and hydrochloric acid, 96 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS &c., substituted hydroxylamines being formed as intermediate products (V. Meyer, B. 1892, 25, 1714). 2. Primary (.CH 2 -N0 2 ) and secondary (:CH-N0 2 ) nitro- compounds can yield metallic derivatives, and hence possess certain acidic properties. For example, nitro-methane and mtro-ethane react with alcoholic sodium hydroxide, yielding sodium compounds, CH 2 Na.N0 2 and CH 3 CHNa N0 2 . It is almost certain that these sodium salts are not true derivatives of the nitro-compound, but are derived from an isomer, the so-called iso-nitro- compound CH 2 :N^Vv TT, and thus sodic nitro-methane has the constitutional formula CH 9 :NO'ONa (Hcllemann, B. 1900, 33, 2913). The nitro-derivatives are t/hus not true acids, but pseudo acids (Hantzsch, B. 1899, 32, 1)77; see also Phenylnitromethane)> These sodium salts are crystalline solids, and are highly explosive. Tertiary nitro-compounds (:C-N0 2 ) contain no hydrogen joined to the carbon atom which is united to the nitro-group, and they have not an acid character; the acidifying influence of the nitro-group does not, therefore, extend to those hydrogen atoms which are attached to other carbon atoms. The hydrogen in the primary and secondary nitro-deriva- tives, which is attached to the same carbon atom as the N0 2 group, can also be replaced by bromine. So long as hydrogen, as well as this bromine and the nitro-group, remains joined to the carbon atom in question, the compound is of a strongly acid character; but when it also is substituted by bromine, the compound becomes neutral, e.g. dibromo-nitro- ethane, CH 3 -CBr 2 .N0 2 , is neutral. The reactivity of the hydrogen atoms of the CH 2 X0 2 and ^>CHN0 2 groups, characteristic of primary and secon- dary nitro-compounds, is exemplified in the reactions of these compounds with aldehydes in the presence of sodium carbonate. A primary nitro-compound can combine with one or with two molecules of formaldehyde, yielding com- pounds of the types - CH(N0 9 )CH 2 . OH and -C(N0 2 ) (CH 2 .OH) 2 . 3. The primary nitro-compounds yield, with concentrated hydrochloric acid at 140, acids of the acetic series containing an equal number of carbon atoms, and hydroxylamine. 4. The reaction of the nitro-compounds with nitrous acid is very varied, The primary yield nitrolic acids and the ESTERS OF SULPHURIC ACID 97 secondary pseudo-nitrols, while the tertiary do not react with it at all. Thus from nitro-ethane, CH 3 .orfJ^ , ethyl- TVT f"\"llT ^^^2 nitrolic acid, CH 3 .C^ N Q , an acid crystallizing in light- yellow crystals and yielding intensely red alkali salts, is formed. Normal nitro-propane acts similarly. Secondary nitro- propane, (CH 3 ) 2 : CHN0 2 , gives, on the contrary, propyl-pseudo-nitrol, (CH 3 ) 2 C(NO)(N0 2 ), a white crystalline, indifferent, non-acid substance, which is blue either when fused or when in solution. These reactions, which are only given with compounds of low molecular weight (in the primary up to C 8 , and in the secondary up to C 5 ), are specially appli- cable for distinguishing between the primary, secondary, or tertiary nature of an alcohol (see p. 74). The nitre-hydro- carbons, which are readily prepared from the iodides, are dis- solved in a solution of potash to which sodium nitrite is added, the solution acidified with sulphuric acid and again made alkaline, and then observed for the production of a red coloration (primary alcohol), a blue coloration (secondary alcohol), or no coloration (tertiary alcohol). Chloropicrin, CC1 3 N0 2 , a heavy liquid of excessively suffo- cating smell, b.-pt. 112, is formed from many hydrocarbon coiri pounds by the simultaneous action of nitric acid and chlorine, chloride of lime, &c. It is best obtained from jpicric acid and bleaching-powder. Polynitro -derivatives are also known. Dinitromethane, CHo(N0 2 ).j, an unstable yellow oil; dinitroethane, CH 3 CH (N0 2 ) 2 , obtained from CH 3 CHBr.N0 2 and potassium nitrite, b.-pt. 185; trinitromethane or nitroform, CH(N0 2 ) 3 , colour- less crystals, m.-pt. 15; tetranitromethane, C(N0 2 ) 4 , colour- less crystals, m.-pt. 13 and b.-pt. 126, is prepared by the action of nitric acid (D = T53) on acetic anhydride (Chatta- way, J. C. S. 1910, 2100). Good yields (50 per cent) of dinitro- compounds of the type N0 2 .[CH 2 ] n .N0 2 can be obtained from the corresponding di-iodo-derivatives and silver nitrite (Fan Bmun and SolecU, B. 1911, 44, ii526) provided n > 3. The compounds are stable and react with bromine, nitrous acid, &c., in much the same manner as mono-nitro-compounds. They are accompanied by alkylene dinitrites, 0:N-0[CH 2 ] n .O'N:0, and nitro-nitrites, N0 2 -[CH 2 ] n -O.N:0, from which they can be separated by fractional distillation. The dinitro-compounds can be used for the preparation of dialdehydes, since when ( B 480 ) Q 98 IV. DERIVATIVES OF MONOHVDRIC ALCOHOLS reduced with stannous chloride they yield dioximes, and these on hydrolysis give dialdehydes: N0 2 .[CH 2 ] 5 -N0 2 -> OH.N:CH.[CH 2 ] 3 .CH:N.OH -> 1:5 Dinitro pentane : CH [CH 2 ] 3 CH : O Glutaric aldehyde. ESTERS OF SULPHURIC ACID As a dibasic acid sulphuric acid can give rise to both neutral or normal esters, e.g. (C 2 H 5 ) 2 S0 4 , and acid esters or alkyl hydrogen sulphates, e.g. C 2 H 5 HS0 4 . The neutral esters are formed by the three general methods : (a) from fuming sulphuric acid and alcohol; (b) from silver sulphate and alkyl iodide; (c) from sulphury! chloride and alcohol : S0 2 C1 2 + 2C 2 H 6 OH = S0 2 (OC 2 H 6 ) 2 + 2HC1 The acid esters of the primary alcohols are generally pre- pared directly from their components. Secondary and tertiary alcohols do not yield them. Ethyl sulphate, (62115)2804, is a colourless oily liquid of an agreeable peppermint odour, insoluble in water, and solidi- fying on exposure to a low temperature. It boils at 208, is quickly hydrolysed with boiling water, but only slowly with cold water, yielding alcohol and sulphuric acid. Methyl sulphate, (CH 3 ) 2 S0 4 , is a syrupy oil, b.-pt. 188, it is extremely poisonous, does not adhere to glass, and is a common reagent used instead of methyl iodide for the forma- tion of methyl derivatives of phenols, alcohols, and amines (cf. S. J., Exp. 127). Ethyl hydrogen sulphate, C 2 H 5 O.S0 2 -OH (Dabit, 1802), is obtained from a mixture of alcohol and sulphuric acid, but not quantitatively, on account of the state of equilibrium that ensues. It is also formed from ethylene and sulphuric acid at a somewhat higher temperature. It differs from sulphuric acid by its Ba-, Ca-, and Pb-salts being soluble, and it can therefore be easily separated from the former by means of BaC0 3 , &c. It yields salts which crystallize beautifully, e.g. KC 2 H 5 S0 4 , but which slowly decompose into sulphate and alcohol on boiling their concentrated aqueous solution, espe- cially in presence of excess of alkali. These salts are frequently used instead of ethyl iodide for the preparation of other ethyl derivatives (process of ethylation). SULPHONIC ACIDS AND DERIVATIVES 99 The free acid ester is prepared by adding the requisite amount of sulphuric acid to the barium salt. It is a colourless oily liquid which does not adhere to glass, and which slowly hydrolyses when its solution is evaporated or kept. When heated alone it is decomposed into ethylene and sulphuric acid; with alcohol it yields ethyl ether and sulphuric acid. DERIVATIVES OF SULPHUROUS ACID a. Alkyl Sulphites. Ethyl sulphite, S0 3 (C 2 H 5 ) 2 , is an ethereal liquid of peppermint odour, which can be prepared from alcohol and thionyl chloride, SOC1 2 , and which is rapidly hydrolysed by water. It has b.-pt. 161, and its probable con- stitution is: 0:S(OEt) 2 . Ethyl Hydrogen Sulphite. The very unstable potassium salt, OEt-S0 9 K, is formed by the action of dry sulphur di- oxide on potassium ethoxide (Rosenheim, B. 1905, 38, 1301). It is decomposed by water, yielding alcohol and potassium sulphite. The action of sodium hydroxide on ethyl sulphite does not hydrolyse the ester to sodium ethyl sulphite, but to sodium ethyl sulphomite, C 2 H 5 S0 2 ONa. (B. 1898, 31, 406.) 13. Sulphonic Acids. Sulphonic acids contain the mono- valent group .S0 2 -OH. They are colourless oils or solids, extremely hygroscopic, readily soluble in water, and are strong monobasic acids. They are much more stable than the iso- meric alkyl hydrogen sulphites; for example, they are not hydrolysed when boiled with aqueous alkalis or acids, but are decomposed when fused with potash. They are non-volatile with steam, and when strongly heated decompose. Ethyl-sulphonic acid, C 2 H 5 .S0 2 .QH (Lowig, 1839; H. Kopp, 1840), is a strong monobasic acid, and yields crystalline salts, e.g. C 2 H 5 .S0 3 K + H 2 (hygroscopic), C 2 H 5 .S0 3 Na + H 2 0. Methyl-sulphonic acid, CH 3 .S0 3 H, is a syrupy liquid, and was prepared by Kolbe in 1845 from trichloro-methyl-sulphonic chloride, CC1 3 .S0 2 C1 (produced from CS 2 , Cl, and H 2 0). Modes of Formation. 1. From sodium or ammonium sulphite and alkyl iodide (or alkyl hydrogen sulphate: Sulphonic esters are formed by the action of alkyl iodides on silver sulphite: 2C 2 H 5 I + Ag 2 S0 3 = (C 2 H 6 ) 2 S0 3 + 2AgI. 100 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS 2. By the oxidation of mercaptans by KMn0 4 or HN0 3 : C 2 H 6 -SH + 30 = C 2 H 5 -S0 3 H. The sulphonic acids yield chlorides with PC1 5 , e.g. ethyl- sulphonic acid gives ethyl-sulphonic chloride, C 2 H 5 'SOgCl, a liquid which boils without decomposition at 177, fumes in the air, and is reconverted by water into ethyl-sulphonic and hydrochloric acids. Nascent hydrogen reduces it to mercaptan, and with zinc dust it yields the zinc salt of a syrupy, readily soluble acid, viz. ethyl-sulphinic acid, C 2 H 5 S0 2 H, which may also be reduced to mercaptan. Sodium ethyl sulphinate yields ethyl sulphone when treated with ethyl bromide, C 2 H 5 Br. When esterified the acid forms an unstable ester, isomeric with ethyl sulphone (B. 24, 2272). Ethyl Ethyl-sulphonate, C 2 H 5 -S0 2 'OC 2 H 5 , is isomeric with ethyl sulphite, and, being an ester of the more stable ethyl- sulphonic acid, can only be partially hydrolysed. It is pre- pared from silver sulphite and ethyl iodide. It boils at 213, and the sulphonic esters generally have considerably higher boiling-points than the isomeric alkyl sulphites. Constitution. From the formation of the sulphonic acids from mercaptans by oxidation, and the (indirect) reversibility of this reaction, it follows that the sulphur in them is directly attached to the alkyl radical; if, then, sulphur is regarded as hexavalent, ethyl-sulphonic acid has the constitution C 2 H 6 .S0 2 -OH = This constitution is in perfect harmony with the reaction of the acids with phosphorus pentachloride and also with their monobasicity. From this we might conclude, assuming that the conversion of metallic sulphites into sulphonic acid deriva- tives is a simple exchange of alkyl and metallic radicals, that the constitution of sodium sulphite is Na-S0 2 ONa, of the hypothetical sulphurous acid HS0 2 OH, and of sulphuric acid OH-S0 2 OH. The alkyl sulphites formed from thionyl chloride probably have the alkyl groups attached to oxygen, e.g. ethyl sulphite, SO(OC 2 H 6 ) 2 . Esters of phosphoric acid PO(OK) 3 , PO(OE) 2 (OH), and PO(OR)(OH) 2 , (K = alkyl), exist, as do also similar com- pounds of phosphorous and hypophosphorous acids. The phosphinic acids, &c., are related to the two last-mentioned classes. Esters of boric and silicic acids are also known. REACTIONS OF NITRIDES; ; >>"h " ^^1 ALKYL DERIVATIVES OF HYDROCYANIC ACID Hydrocyanic acid, HCN, yields two classes of derivatives by the exchange of its hydrogen atom for alkyl radicals, neither of which can be regarded as esters, in the sense that they are hydrolysed to the acid and alcohol. a. Alkyl Cyanides or Nitriles, E-C-N. These are either colourless liquids, which volatilize without decomposition, or solids, with an ethereal odour slightly resembling that of leeks; they are lighter than water, and are relatively stable. The lower members are miscible, with water, but the higher ones not, and they boil at about the same temperatures as the corresponding alcohols. Formation. 1. By heating an alkyl iodide with an alcoholic solution of potassium cyanide, or potassium ethyl -sulphate with potassium ferrocyanide : CH 3 I + KCN = Kl-f CH 3 . ON (methyl cyanide). 2. From fatty acids, e.g. acetic acid, CH 3 -CO.OH. The ammonium salt when distilled loses water and yields the acid amide, e.g. : CH 3 .CO-ONH 4 = H 2 O + CH 3 .CO-NH 2 (acetamide). The amide when heated with a dehydrating agent, e.g. P 4 10 , loses a second molecule of water and yields the cyanide : CH 3 -CO.NH 2 = H 2 O + CH 3 -C:N. As a consequence of this mode of formation these com- pounds are also termed nitriles of the monobasic acids, e.g. CHg-CN, methyl cyanide or aceto-nitrile ; C 2 H 5 -CN, propio- nitrile, &c. 3. The higher nitriles, in which C>5, are formed from the amides of acids of the acetic series containing 1 atom of carbon more in the molecule, and also from the primary amines with the same number of carbon atoms, upon treatment^with bro- mine and caustic-soda solution (Hofmann). See Amides. 4. From the oximes of the aldehydes, by warming with acetic anhydride. See Aldoximes. Reactions. The nitriles are chemically active. Most of the reactions are of an additive nature, and are somewhat similar to those characteristic of the olefines. These reactions are in harmony with the constitutional formulae usually attributed to the nitriles, e.g. R.C|N, according to which a triple bond exists between a nitrogen and a carbon atom. 102 . 'f.V.ERrtfATIYES OF "MONOHYDRIC ALCOHOLS 1. When hydrolysed with acids or alkalis, or superheated with water, they take up water (2 mols.) and yield the ammonium salts of fatty acids (with alkalis, the alkali salt, and free ammonia). The reaction undoubtedly proceeds in two distinct stages, and an acid amide is first formed: CH 3 .CO-NH 2 -fH 2 = CH 3 .CO.ONH 4 . It is generally impossible to stop the hydrolysis at the first stage in the case of aliphatic nitriles, but this is readily accomplished with aromatic cyanides. This is a reaction of considerable interest, as it enables us to pass from a saturated alcohol, C n H 2n+1 -OH, to the aliphatic acid, C n H ta+1 COOH, which contains 1 atom of carbon more than the alcohol: CH 3 .OH -> CH 3 I - CH 3 .CN CH 3 .COOH. 2. Just as acetamide is formed by the taking up of water, so is thio-acetamide by the addition of sulphuretted hydrogen, 3. By the addition of hydrochloric acid, amido-chlorides or imido-chlorides are formed ; by the addition of ammonia bases, amidines. Halogens also form decomposable additive-products. 4. Primary amines are obtained by the reduction of nitriles with sodium and alcohol (p. 106): CH 3 .C!N + 4H = CH 3 .CH 2 .NH 2 (ethylaimne). 5. Metallic potassium or sodium frequently induces poly- merization; thus methyl cyanide yields in this way cyan- methine, a mono-acid base crj^stallizing in prisms. Aceto-nitrile, Ethane-nitrile, CH 3 CN, b.-pt. 82 is present in the products of distillation from the vinasse of sugar beet and in coal-tar. Propio-nitrile; (Propane-nitrile), C 2 H 5 'CN, butyro- nitrile, C 3 H 7 'CN, and valero-nitrile, C 4 H 9 CN, are liquids of -agreeable bitter-almond-oil odour; palmito-nitrile, C 15 H 31 CN, is like paraffin. P. Isocyanides, Isonitriles or Carbylamines. These are colourless liquids readily soluble in alcohol and ether, but only slightly soluble in water. They have a feeble alkaline reaction, an unbearable putrid odour, and poisonous proper- ties, and boil somewhat lower than the isomeric nitriles. Formation. 1. By heating an alkyl iodide with silver cyanide instead of potassium cyanide (Gautier), a double com- CONSTITUTION OF CYANIDES AND ISOCYANIDES 103 pound with silver cyanide being first formed, according to Wade : Ag-N:C: + EtI = EtANzC: = AgI + Et-N:C: I' (ethyl carbylamine). 2. In small quantity, along with the nitrile, when a potassium alkyl-sulphate is distilled with potassium cyanide. 3. By the action of chloroform and alcoholic potash upon primary amines (Hofmann, 1869) (see pp. 63 and 108): CH 3 .NH 2 + CHC1 3 + 3KOH = CH 3 .N:C + 3KC1 + 3H 2 O. Behaviour. 1 . The isonitriles differ fundamentally from the nitriles in their behaviour with water or dilute acids. When strongly heated with water, or with acids in the cold, they decompose into formic acid and a primary amine containing an atom of carbon less than themselves: Unlike the nitriles, they are very stable towards alkalis. 2. The isonitriles are also capable of forming additive pro- ducts with the halogens, HC1, H 2 S, &c., compounds different from those given by the nitriles; thus, with HC1 they yield crystalline salts which are rapidly decomposed by water into amine and formic acid. 3. Some of the isonitriles change into the isomeric nitriles when heated. According to Wade this change does not occur at all readily in the fatty series if the carbylamines are thoroughly dry. (J. C. S. 1902, 81, 1596.) Methyl isocyanide, CH 3 -NC, boils at 58, and ethyl iso- cyanide, C 2 H 5 NC, at 82. Constitution of the Nitriles and Isonitriles. The constitution of the nitriles follows from the readiness with which they can be hydrolysed to acids of the acetic series. In acetic acid we know that we have a methyl group directly attached to a carbon atom, e.g. CH 3 CO OH, and since methyl cyanide on hydrolysis yields acetic acid, it also presumably contains the methyl group attached to carbon. The nitrogen atom, on the other hand, is eliminated, and is thus probably not directly bound to the alkyl radical. Consequently aceto-nitrile has the constitution CH 3 C:N. This constitutional formula is supported by a study of the product formed on reduction, namely CH 3 CH 2 NH 2 . 104 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS In the case of the isonitriles, however, it is the nitrogen which must be directly bound to the alkyl radical, as their close connection with the amine bases shows, the amines being easily prepared from and reconverted into the isonitriles. The carbon atom of the cyanogen group, on the contrary, is eliminated as formic acid on decomposition with acid, and is consequently not directly united to the alkyl radical, but only through the nitrogen. The constitutional formula of methyl isocyanide is therefore either CH 3 N:C or CH 3 -N:C:, with an unsaturated carbon atom (cf. Chap. LII). D. Amines or Nitrogen Bases of the Alkyl Radicals By the introduction of alkyl radicals in place of hydrogen into the ammonia molecule, the important class of ammonia bases or amines is formed. The amines containing small alkyl groups bear the closest resemblance to ammonia, and are even more strongly basic than the latter. They have an ammoniacal odour, give rise to white clouds with volatile acids, combine with hydro- chloric acid, &c,, to salts with evolution of heat, and yield platini- and auri-chlorides. Their aqueous solutions precipitate insoluble hydroxides from solutions of the salts of the heavy metals, and these precipitates are frequently soluble in excess. The lowest members of this class are combustible gases readily soluble in water. The next are liquids of low boiling- point, also at first readily soluble; but the solubility in water, and also the volatility, decrease with an increase in molecular weight, until the highest members of the series, such as tricetyl- amine, (C 16 H 33 ) 3 N, are at the ordinary temperature odourless solids of high boiling-point, insoluble in water but soluble in alcohol and ether, and readily combining with acids to form salts. All amines are considerably lighter than water. The quaternary ammonium hydroxides are solid and very hygroscopic, and exceedingly like potash in properties. Classification. The bases are divided into primary, secondary, tertiary, and quaternary bases, according as they contain 1, 2, 3, or 4 alkyl radicals; the three first are derived from am- monia, and the last from the hypothetical ammonium hy- droxide, NH 4 .OH. Characteristic of primary amines is the amino group, 'NHg, of secondary, the imino group, :NH, and of tertiary, the N radical attached to three alkyl groups. FORMATION OF AMINES 105 The system of nomenclature is simple, as indicated by the following examples: CH 3 NH 2 , methylamine ; C 3 H 7 'NH 2 , propylamine; (C 2 H 5 ) 2 NH, di-ethylamine; (CH 3 ) 3 N, trimethyl- amine; and N(C 2 H 5 ) 4 I, tetraethylammonium iodide. The alkyl radicals may be either saturated or unsaturated. Modes of Formation. 1. Primary amines, e.g. methylamine, ethylamine, are obtained by heating alkyl cyanates with potash solution (Wurtz, 1848), just as cyanic acid itself yields ammonia and carbon dioxide : 2. By the direct' introduction of the alkyl radical into ammonia by heating a concentrated solution of the latter with methyl iodide, chloride, or nitrate, ethyl iodide, &c. In this reaction an atom of hydrogen is first exchanged for an alkyl radical, and then the base produced combines with the halogen hydride, formed at the same time, to a salt, thus : (I) NH 2 H + CH 3 I = NH 2 .CH 3 , HI. From the methylamine hydriodide thus produced, free methylamine can readily be obtained by distillation with potash : NH 2 (CH 3 ), HI + KOH = NH 2 (CH 3 ) + KI + H 2 O. The methylamine can now combine further with methyl iodide to hydriodide of dimethylamine : (II) NH 2 (CH 3 ) + CH 3 I = NH(CH 3 ) 2 HI, tthich, in its turn, yields the free base with potash. This latter can again combine with methyl iodide: (III) NH(CH 3 ) 2 + CH 3 I = N(CH 3 ) 3 HI, the salt so produced yielding trimethylamine as before. Finally, the trimethylamine can once more take up methyl iodide : (IV) N(CH 3 ) 3 + CH 3 I = N(CH 3 ) 4 I. The compound obtained, tetramethylammonium iodide,^ is, however, no longer a salt of an amine, but of an ammonium base, and is not decomposed on distillation with potash solu- tion. The velocities of formation of quaternary ammonium iodides from tertiary amines and alkyl iodides have been determiner! bv Menwhutkin. The reaction has been shown 106 IV. DEBIVATIVES OP MONOHYDRIO ALCOHOLS to be a bimolecular one. The velocity varies with the alkyl iodide employed, decreasing as the alkyl group becomes more complex. The solvent employed, for example, acetone, hexane, methyl alcohol, &c., also affects the velocity of formation to an enormous extent, e.g. the combination of ethyl iodide and try-ethylamine takes place some 250 times as readily in ethyl alcohol as in hexane solution. Primary and secondary bases can also be transformed into secondary and tertiary by warming with potassium alkyl- sulphates (B. 1891, 24, 1678). When, several alkyl iodides are used in place of methyl iodide, mixed amines, i.e. amines containing different alkyl ups in the molecule, are obtained, e.g. methyl-propylamine, H(CH 3 )(C 3 H 7 ), methyl-ethyl-propy'lamine, N(CH 3 )(C 2 H 5 ) (C 3 H r ). The reactions I to IV given above do not in reality follow each other in perfect order but go on simultaneously, the bases being partly liberated from the hydriodides by the ammonia, and so being free to react with more alkyl haloid. The pro- duct obtained by distillation with potash is therefore a mixture of all the three amines and ammonia. These cannot be separated by fractional distillation, and so their different behaviour with ethyl oxalate, OEt-CO-CO-OEt, is made use of for the purpose. Methyl amine reacts with this ester to form chiefly (1) dimethyl-oxamide, CH 3 NH. CO -CO- NK CH 3 (solid), and (2) some methyl-oxamie ester, OEt CO CO-NH-CH 3 (liquid); dimethylamine yields (3) the ethyl ester of dimethyl-oxamic acid, OEt-CO-CO-N(CH 3 ) 2 (liquid), while trimethylamine does not react with the ethyl oxalate. Upon warming the product of the reaction on the water-bath, the latter base distils over, and the remaining compounds can then be separated by special methods (for which see B. 3, 776; 8, 760), and individually decomposed by potash, (1) and (2) yielding methylamine, and (3) dimethylamine. 3. The nitro-compounds yield primary amines when treated with acid reducing agents (see p. 95), thus : CH 3 .N0 2 -f 6H = CH 3 .NH 2 + 2H 2 0. 4. The nitriles, including hydrocyanic acid, are capable of taking up four atoms of hydrogen (see p. 102) and forming primary amines (Menditis, 1862): CH 3 .C:N + 4H = CH 3 -CH 2 .NH 2 (ethylamine). PROPERTIES OF AMINES 107 5. Primary amines, in which C < 6, are prepared according to Hofmann's method, by the action of bromine and caustic- soda solution upon the amides of acids containing 1 carbon atom more than themselves (see Amides). 6. Primary amines likewise result from the reduction of the oximes or hydrazones (see pp. 127 and 135): for example, acetaldoxime : CH 3 .CH:N.OH-]-4H = CH 3 .CH 2 .NH 2 + H 2 O. 7. See p. 463 for preparation of amines from phthalimide. Isomers. Numerous isomers exist among the amines, as the following table shows : C 2 H 7 N. C 3 H 9 N. C 4 H n N. Isomers NH 2 (C 2 H 5 ) NH(CH 3 ) 2 NH 2 (C 3 H 7 ) NH(CH 3 )(C 2 H 6 ) N(CH 3 ) 3 NHo(C 4 H 9 ) NH(CH S )(C 8 H T ) and NH(C 2 H 5 ) 2 N(CH 3 ) 2 (C 2 H 6 ) This kind of isomerism is the same as that of the ethers (p. 87), i.e. metamerism. From (C 3 H r ) onwards, isomerism can also occur in the alkyl radicals. According to theory, as many amines C n as alcohols C n+1 are capable of existence. Behaviour. 1. The amines combine directly with acids (or- ganic or inorganic) to form salts in exactly the same way as ammonia; the quaternary ammonium bases, however, react with acids, forming salts and eliminating water like potassium or ammonium hydroxide : CH 3 .NH 2 + HC1 = CH 3 .NH 2 , HC1 = CH 3 .NH 3 CL (CH 3 ) 4 N.OH + HC1 = (CH 3 ) 4 N.C1 + H 2 O. The salts so obtained are white, crystalline compounds, readily soluble in water, and frequently hygroscopic. The chlorides form, with platinic chloride, sparingly soluble platini- chlorides analogous to ammonium platinichloride, (NH 4 ) 2 PtCl 6 , e.g. methylamine platinichloride, (CH 3 NH 3 ) 2 PtCl 6 . The same applies to the aurichlorides, e.g. C 2 H 5 NH 3 AuCl 4 . Strong alkalis, e.g. potassium hydroxide, decompose all the salts with the exception of the quaternary ammonium com- pounds yielding the free bases (and not ammonia). 2. Hydrolysing agents such as alkalis and acids do not affect the nitrogen bases of the alcohol radicals. 3. The different classes of amines are distinguished from 108 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS each other by the primary having 2 hydrogen atoms, the secondary 1, but the tertiary none replaceable by alkyl groups; the same applies to acid radicals (acyl groups). The ultimate products obtained from isomeric amines by the action of methyl iodide are distinguished from one another by ana- lysis. Thus of the three isomeric amines C 3 H 9 N, propylamine gives with methyl iodide, C 8 H 7 .N(CH 3 ) 3 I, propyl-trimethyl- ammonium iodide = C 6 H 16 NI; methyl-ethylamine gives C 2 H 5 N(CH 3 ) 3 I, ethyl-trimethylammonium iodide = C 5 H 14 NI; and trimethylamine gives N(CH 3 ) 4 I, tetramethylammonium iodide = C 4 H 12 NI. An iodine estimation in the final product would immediately enable us to settle the constitution of the original amine. The primary bases further differ from the others in their behaviour with chloroform, carbon disulphide, and nitrous acid. 4. Only the primary bases react with chloroform and alco- holic potash, with formation of isonitriles (p. 103). 5. When warmed with carbon disulphide in alcoholic solu- tion, the primary and secondary, but not the tertiary, bases react to form derivatives of thiocarbamic acids. (See Carbonic Acid Derivatives.) Should the amines be primary ones, the characteristically smelling isothiocyanates are produced upon heating the thiocarbamic derivatives with a solution of HgCl 9 (" Senfol " reaction). 6. Nitrous acid reacts with the primary amines, forming alcohols, e.g. A molecular rearrangement is occasionally met with, e.g. the production of isopropyl alcohol from ?i-propylamine. Secondary bases yield with nitrous acid nitroso-compounds, e.g. " diinethyl-nitrosamine " : (CH 3 ) 2 NH + NO.OH = (CH 3 ) 2 N.NO + H 2 0. These nitrosamines are yellow-coloured volatile liquids of aromatic odour (Geuther). When reduced with acid-reducing agents, or when heated with alcohol and hydrochloric acid, they regenerate the secondary amines. Weak reducing agents, however, convert them into hydrazines (p. 112). The nitros- amines are frequently of great service in the purification of the secondary bases. Nitrous acid has no action upon tertiary amines. 7. By the indirect action of nitric acid (B. 22, Ref. 295), PROPERTIES OF AMINES 109 nitr amines result, i.e. amines in which an amino-hydrogen atom has been replaced by the nitro- group, e.g. CH 3 .NH.N0 2 , methyl-nitramine. Similarly, by the indirect introduction of an amino-group, hydrazines are formed, e.g. CH 3 NHNH 2 , methyl-hydrazine. 8. While the amines are liberated from their salts by alkalis, the free bases of the quaternary ammonium salts, e.g. tetra- methylammonium iodide, cannot be prepared from these by treatment with potash, because the products are soluble and non-gaseous, and hence an equilibrium is attained. The salts behave normally in aqueous solutions, for example, the iodides yield precipitates with silver nitrate, and are good electrolytes, The corresponding hydroxides, e.g. N(CH 3 ) 4 OH, are obtained most readily by acting upon the iodides with moist silver oxide. These hydroxides are extraordinarily like caustic potash. They are colourless hygroscopic solids, readily soluble in water, and abstract carbon dioxide from the air. The solu- tions have strongly alkaline properties, are good electrolytes, and precipitate metallic hydroxides from solutions of their salts. When distilled they decompose, yielding the tertiary base, the tetramethyl base yielding in addition methyl alcohol, and the homologous bases olefine and water (Braun, A. 382, 1): N(CH,),.OH = N(CH 3 ) 3 +CH 3 .OH. N(C 2 H 6 ) 4 .OH = They are of importance for the study of the valency of nitrogen. Their formation and general properties are most in harmony with the assumption of a penta- or quinque-valent PTT / 3 nitrogen atom, e.g. 3 />N-CH 3 , and not as a so-called mole- cular compound, N(CH 3 ) 3 , CH 3 I. (Cf. Trimethyl-sulphonium hydroxide.) The fact that the salts N(CH 8 )(C 2 H 6 ) + C^Cl and N(CH 3 )(C 2 H 5 ) 2 + CH 3 C1 are identical, is in agreement with the former assumption. (Meyer and Lecco.) Lastly, optically active isomers are met with among the quaternary ammonium salts, a point which receives its readiest explanation from the asymmetry of the molecule containing a quinquevalent nitrogen atom. (See Stereochemistry of Nitrogen Derivatives.) 9. The quaternary iodides are resolved into tertiary base and alkyl iodide when heated. They combine with 2 or 4 atoms of bromine or iodine to tri- and penta-bromides or -iodides, e.g. N(CH 3 ) 4 .U 4 (dark needles), and N(C 2 H 5 ) 4 M 2 110 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS (azure-blue needles). Such periodides readily lose the excess of iodine, and are hence relatively unstable. Hepta- and Ennea- iodides also exist. The following table gives the boiling-points of the various amines:- Primary. Secondary. Tertiary. Methyl . . 6 7 3'5 Ethyl 19 56 90 ft-Propyl 49 98 156 w-Butyl . . 76 160 215 7i-0ctyl 180 297 366 Methylamine, CH 3 NH 2 , occurs in Mercurialis perennis and annua (" mercurialin "), in the distillate from bones and wood, and in herring brine. It is produced in many decom- positions of organic compounds, e.g. from alkaloids, as when caffeine is boiled with barium hydroxide; also by heating trimethylamine hydrochloride to 285. It is most readily prepared from acetamide, caustic soda, and bromine. (B. 18, 2737.) It is more strongly basic and even more soluble in water than ammonia, has a powerful ammo- niacal and at the same time fishlike odour, and burns with a yellowish flame. Its aqueous solution, like that of ammonia, precipitates many metallic salts, frequently redissolving the precipitated hydroxides; unlike ammonia, it does not dissolve Ni(OH)2 and Co(OH),. The hydrochloride, CH 3 NH 2 , HC1, forms large glistening plates, is very hygroscopic and readily soluble in alcohol; the platinichloride crystallizes in golden scales, and the sulphate forms an alum. Dimethylamine, (CH 3 ) 2 NH, occurs in Peruvian guano and pyroligneous acid, and is formed by decomposing nitroso-di- methyl-aniline by caustic-soda solution. Trimethylamine, (CH 3 ) 3 N, is widely distributed in nature, being found in considerable quantity in Chenopodium vulvariu, also in Arnica montana, in the blossom of Cratcegus oxyacantlw, and of pear, and in herring brine. (Werthdm.) It is a decomposition product of the betaine of beet-root, and therefore along with ammonia, dimethylamine, &c., methyl alcohol and aceto - nitrile by the distillation of II YDBOXYL AMINES AND HYI'BAZISES 111 vinasse. It has an ammoniacal and pungent fishlike odour. The tertiary amines can be oxidized by means of hydrogen peroxide to compounds of the type (CH 3 ) 3 N : 0, trimethyl- amine oxide, whijh are colourless crystalline bases. Tetramethylammonium iodide, N(CH S ) 4 I, is obtained in large quantity directly from IS[H 3 + CH 3 I. It crystallizes in white needles or large prisms, and has a bitter taste. Tetramethylammonium hydroxide, N(CH 3 ) 4 OH, crystallizes in hygroscopic needles, and can be obtained by the action of alcoholic potash on an alcoholic solution of its chloride; potas- sium chloride is precipitated, and the hydroxide remains in solution. It forms salts, e.g. a platinichloride, sulphide, poly-' sulphide, cyanide, &c. Ethylamine, C 2 H 6 NH 2 . Crude ethyl chloride (obtained as a by-product in the manufacture of choral) is used for its pre- paration. It has a strongly ammoniacal smell and biting taste, mixes with water in every proportion, and burns with a yellow flame. It dissolves A1(OH) 3 , but not Fe(OH) 3 ; also Cu(OH) 2 with difficulty, but not Cd(OH) 2 . With bleaching powder it yields ethyl-dichloro-amme, C 2 H 5 'NC1 2 , as a yellow oil of a most unpleasant piercing odour. Tri-ethylamine, (C 2 H 5 ) 3 N, is an oily strongly alkaline liquid. The precipitates which it gives with solutions of metallic salts are mostly insoluble in excess of the precipitant. HYDROXYLAMINES ; HYDRAZINES The Alkyl-hydroxylamines, which are derived from hy- droxylamine, NH 2 OH, just as the amines are from ammonia, belong to two different series, in accordance with the constitu- tion of hydroxylamine, thus : NH 2 .OCH 3 and CHg-NH-OH a-Methyl-hydroxylamine /3-Methyl-hydroxylamine. The compounds of the first series, which are obtained from the oxime ethers (p. 138), are as ethereal compounds toler- ably stable, and do not reduce Fehling's solution. Those of the second series, which likewise result from certain pxime derivatives, but at the same time also from the reduction of the nitro-hydrocarbons (p. 96), very readily undergo change, reduce Fehling's solution even in the cold, and yield primary amines when further reduced (B. 23, 3597; 24, 3528; 25, 1714). E. Fischer (A. 190, 67; 199, 281, 294) has given the name of hydrazines to a series of peculiar bases, mostly liquid and 112 IV. DERIVATIVES OF MONOHYDRIO ALCOHOLS closely resembling the amines, but containing two atoms oi nitrogen in the molecule, and differing from the latter espe- cially by their capability of reducing Fehling's solution, for the most part even in the cold, and by the ease with which they are oxidized. They are derived from "Diamide" or "Hydra- zine", NH 2 -NH 2 (Curtius and Jay, J. pr. Oh. 1889, (2), 39, 27) They are formed by the action of nascent hydrogen on the nitrosamines (p. 108): (CH 3 ) 2 N.NO + 4H = (CH 3 ) 2 N.NH 2 + H 2 0. Primary, secondary, tertiary, and quaternary hydrazines are known, according as 1, 2, 3, or 4 of the hydrogen atoms in NH 2 NH 2 are replaced by alkyl groups. The secondary hydrazines exist in two isomeric forms, namely, NHR NHR arid NH 2 NR 2 , which are known respec- tively as symmetrical and unsymmetrical secondary hydrazines. Methyl-hydrazine, CH 3 .NH.NH 2 (cf. A. 1889, 253, 5). An excessively hygroscopic liquid, which fumes in the air, and has an odour similar to that of methylamine. B.-pt. 87. Ethyl-hydrazine, C 2 H 5 .NH-NH 2 . When di-ethyl urea is treated with nitrous acl J a nitroso-compound is formed, which, on reduction with zinc dust and acetic acid, yields the so-called " diethyl-semicarbazide ", and this decomposes, when heated with hydrochloric acid, into carbon dioxide, ethylamine, and ethyl-hydrazine : 2 H 6 N(NO).C 2 H 5 \N(NH 2 ).C 2 H 5 Di-ethyl-urea Nitroso-compound Diethyl-semicarbazide. Ethyl-hydrazine is a colourless mobile liquid of ethereal and faintly ammoniacal odour, boiling at 100. It is very hygroscopic, forms white clouds with moist air, dissolves in water and alcohol with evolution of heat, and corrodes cork and caoutchouc. Diethyl-hydrazine, (C 2 H 5 ) 2 N NH 2 , is prepared from di- ethylamine by transforming it into diethyl-nitrosamine by the nitrous-acid reaction, and then reducing the latter. It resembles ethyl-hydrazine closely: (C 2 H 5 ) 2 N-NO + 4H = Tetra-ethyl-tetrazone, (C 2 H 5 ) 2 :N'N:N.N:(C 2 H 5 ) 2 , PHOSPHINES 113 colourless, strongly basic oil, volatile with steam, is formed when diethyl-hydrazine is heated with mercuric oxide. The constitution of the hydrazines follows from their modes of formation. Since in diethyl-nitrosamine, (C 2 H 5 ) 2 NNO, for instance, the nitroso-group NO must be attached to the nitrogen of the amine and not to the carbon, judging from the ease with which it can be separated (p. 108), so the same linking of the atoms must be assumed in the hydrazines, which are formed from the nitroso-compounds by reduction, i.e. by exchange of for 2H. The readiness with which di- ethyl-hydrazirie is oxidized to diethylamine, e.g. by alkaline cupric oxide, is an agreement with such a formula. The hydrazines are relatively stable towards reducing agents. For aliphatic Diazo and Triazo Compounds, see Chap. LI. E. Alkyl Derivatives of Phosphorus, Arsenic, &c. 1. PHOSPHORUS Just as amines are derived from ammonia, so from phos- phuretted hydrogen, PH 3 , are derived primary, secondary, and tertiary phosphines by the exchange of hydrogen for alkyl radicals, and to these must likewise be added quaternary compounds, the phosphonium bases. The phosphines corre- spond closely with the amines in composition and in some of their properties, e.g. they are not saponifiable. But they differ from them in the following points : 1. Like phosphuretted hydrogen itself, the alkyl phosphines are only feebly basic; thus ethyl phosphine does not affect litmus, and its salts are decomposed by water. The salts of the secondary and tertiary compounds are not decomposed, thus showing that the presence of alkyl radicals tends to strengthen the basic properties of the compound. 2. Like phosphuretted hydrogen they are readily inflam- mable, and they are consequently rapidly oxidized in the air and readily take fire of themselves. 3. As the phosphorus atom in these compounds shows a tendency to pass' from the ter- to the quinque-valent state, many of the phosphines behave as unsaturated compounds; they combine with oxygen, sulphur, halogens, &c., for ex- ample, (CH 3 ) 3 PO, (CH 3 ) 3 PS, (CH 3 ) 3 PC1 2 , and a compound (CH 3 ) 3 P, CS 2 , in the form of red plates. The products ob- tained on oxidation are characteristic, and may be regarded (B480) B 114 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS 03 derived from phosphoric acid, 0:P(OH) 3 , by the replace- ment of one or more OH groups by one or more alkyl radicals : CHg-PHg, with nitric acid,, yields CH 3 -PO.(OH) 2 , methyl phos- phonic acid. (CH 3 ) 2 PH, with nitric acid, yields (CH 3 ) 2 PO OH, dimethyl phos- phinic acid. (CH 3 ) 3 P, on oxidation in the air, yields (CH 3 ) 3 PO, trimethyl phos- phine oxide. 4. Corresponding with the disagreeable smell of phos- phuretted hydrogen, they possess an excessively strong stupefying odour; thus ethyl phosphine has a perfectly over- powering smell, and excites on the tongue and deep down in the throat an intensely bitter taste. Formation. 1. The tertiary phosphines and quaternary compounds are formed directly from phosphine and an alkyl iodide. (Of. Amines, formation 2.) PH 3 + 3C 2 H 6 I = P(C 2 H 6 ) 3 + 2. According to Hofmann (1871), primary and secondary phosphines are formed by heating phosphonium iodide and an alkyl iodide with zinc oxide, e.g. : 2C 2 H 6 I + 2PH 4 I -f ZnO = 2P(C 2 H 6 )H 2 , HI + ZnI 2 + H 2 0. They can be separated from one another by decomposing the salts of the primary phosphines by water, as already mentioned. 3. The tertiary phosphines are produced from calcium phosphide and an alkyl iodide, a reaction first observed by Thenard in 1846; 4. Also from phosphorus trichloride and zinc methyl, or magnesium alkyl iodides (Auger and Billy, C. 1904, 139, 597). 5. The phosphonium salts are formed by the combination of tertiary phosphines with an alkyl haloid, and closely resemble the corresponding ammonium compounds. Tri-ethyl phosphine, P(C 2 H 5 ) 8 , has no alkaline reaction. When concentrated it possesses a stupefying, and when dilute a pleasant hyacinth-like odour. Tetramethyl- phosphonium hydroxide, P(CH 8 ) 4 OH. Un- like the analogous ammonium hydroxide, this compound de- composes into trimethyl-phosphine oxide and methane when heated: P(CH 3 ) 4 OH = P(CH 3 ) 3 O + CH 4 . The tetra-ethyl compound decomposes in a similar manner. /,;_ ARSINES 115 2. ARSENIC The similarity of arsenic to phosphorus and nitrogen is further exemplified by the analogous compounds which it forms with alkyl radicals. In virtue, however, of the more metallic character of arsenic, it does not show the same ten- dency to combine with alkyl radicals and hydrogen at the same time, but forms derivatives containing alkyl groups and electro -negative elements like chlorine or oxygen. Arsenic analogues of methylamine have been recently prepared, and are very unstable. Trimethyl-arsine, analogous to trimethyl- amine and trimethylphosphine, is well known. As primary and secondary compounds we have methyl-arsine dichloride, CH 3 AsCl 2 , dimethyl-arsine chloride, (CH 3 ) 2 AsCl, and analo- gous substances. They are colourless liquids of stupefying odour, exerting in some cases an unbearable irritating action upon the mucous membrane. They do not possess basic pro- perties. In addition to these there exist also quaternary com- pounds, arsonium salts, which are exactly analogous to the quaternary phosphonium salts. The halogen of the chlorine compounds is easily replaceable by its equivalent of oxygen. Thus, corresponding with the compound BAsCl 2 there is an oxide EAsO and a sulphide R.AsS, and with the chloride E 2 AsCl an oxide (R 2 As) 2 0. These oxides, liquid or solid, are compounds of stupefying odour, and behave like basic oxides; hydrochloric acid recon- verts them into the corresponding chlorides. Here, also, the tendency of arsenic to change from the tervalent to the quinquevalent state is especially marked. The above chlorides and trimethyl-arsine itself all combine with two atoms of chlorine to compounds of the type AsX . The above oxygen compounds of the type AsX 3 and also tri- methyl-arsine are consequently oxidizable to compounds con- taining one atom or two OH groups more, acids or oxides which are also formed from the chlorides of the type AsX 5 by exchange of halogen for or OH, e.g. cacodyl oxide, (Me 2 As) 2 0, to cacodylic acid, Me 2 As<^ . These products are therefore completely analogous to the phosphonic and phosphinic acids and phosphine oxides already described. The compounds As(CH 3 ) x Cl c _ x , of the type AsX 5 , when heated, decompose into methyl chloride and compounds As(CH 3 ) x . 1 Cl 4 _ x , of the type AsXg, this elimination of methyl 116 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS chloride taking place the more readily the fewer methyl groups are present in the molecule; thus As(CH 3 ) 3 Cl 2 breaks up when somewhat strongly heated, As(CH 3 ) 2 Cl 3 at 50, and As(CH 3 )Cl 4 at 0, i.e. the last-named is only stable when in a freezing -mixture. When, therefore, chlorine acts upon As(CH 3 )Cl 2 at the ordinary temperature, the reaction appears to be one of direct exchange of alkyl for chlorine, thus : As(CH 3 )Cl 2 -f C1 2 = AsCl 3 + CHjCl. It is interesting to note that, like free " methyl " (CH 3 ), the radical As(CH 3 ) 2 has no separate existence; cacodyl pos- sesses the doubled formula As 2 (CH 3 ) 4 (" Di-arsene-disnethyl rj ). The tertiary arsines are formed : 1. From sodium arsenide and alkyl iodide (Cahours ard Riche): AsNa 3 -f SCgHfil = As(C 2 H 6 ) 3 + 3NaL 2. From arsenious chloride and (a) zinc alkyl (ffofmann),, or (b) magnesium alkyl haloid (Pfeiffer, B. 1904, 37, 4620; Sauvage, C. 1904, 139, 674). Trimethyl-arsine, As(CH 3 ) 3 , and triethyl-arsine, As(C 2 H 5 ) 3 , are liquids sparingly soluble in water. They fume in the air, and are thereby oxidized to tri-methyl- or -ethyl-arsine oxide. The secondary arsines are obtained from cacodyl and cacodyl oxide, which are formed when a mixture of potassic acetate and arsenious oxide is distilled (Cadet, 1760): The distillate of cacodyl and cacodyl oxide so obtained, and termed " alkarsin ", fumes in the air and is spontaneously inflammable (Cadet's "fuming arsenical liquid"). Hydro- chloric acid acts upon it to form cacodyl chloride (Bunsen, 1838), and caustic-potash solution gives pure cacodyl oxide, As 2 (CH 3 ) 4 0, a liquid of stupefying odour which produces nausea and unbearable irritation of the nasal mucous mem- brane; it boils without decomposition, and is insoluble in water and of neutral reaction. It yields salts with acids, e.g. cacodyl chloride with hydrochloric acid: 0(AsMe 2 ) 2 + 2HC1 = 2 AsMe 2 Cl + H 2 O. The chloride is a liquid of even more stupefying odour and violent action than the oxide, and its vapour is spontaneously STIBINES 117 inflammable. When heated with zinc clippings in an atmos- phere of carbon dioxide, it yields the free cacodyl, As 2 (CH 8 ) 4 (from /caKw&ys, "stinking"), a colourless liquid insoluble in water and boiling undecomposed at 170, and of a horrible nauseous odour which produces vomiting. It is as readily inflammable in the air as the vapour of phosphorus, yielding the oxide when slowly brought in contact with it, and also combining directly with sulphur, chlorine, &c. Cacodyl plays, therefore, even down to the most minute particulars, the part of a simple electro-positive element; it is a true "organic element" (Bunseri). PTT O Cacodylic acid, 3 x As \' is crvstalline > sduble in water, odourless, and poisonous. It forms crystallizable salts. SUMMARY Compounds with Chlorine. Oxides. Acids. Primary .. Methyl- arsine dichloride, Methyl- arsine tetra- chloride, Methyl- arsine oxide, Methyl- arsonic acid, 0:AsMe(OH) 2 . AsMeCl 2 . AsMeCl 4 . AsMeO. Solid plates. B.-p. 133. B.-p. 95. Secondary Cacodyl chloride, Cacodyl trichloride, Cacodyl oxide, Cacodylic acid, AsMe 2 Cl. AsMe 2 Cl 3 . (AsMe 2 ) 2 0. O:AsMe 2 -OH. B.-p. 100. B.-p. 150. Prisms. M.-p. 200. Tertiary... Trimethyl- Trimethyl- Trimethyl- arsine, arsine arsine AsMe 3 . dichloride, oxide, B.-p. 70. AsMe 3 Cl 2 . AsMe 3 O. Solid. 3. ANTIMONY, BORON, AND SILICON COMPOUNDS Antimony also forms compounds with the alkyls precisely similar to those of arsenic; primary and secondary compounds do not exist. Trimethyl-stibine, Sb(CH 3 ) 3 (Landolt), is a highly disagreeable and spontaneously inflammable liquid of onion-like smell; and Antimony pentamethyl, Sb(CH 8 ) 5 , an oily liquid of weak odour, which can be distilled, and is not 118 IV. DERIVATIVES OF MftOHYDRtC ALCOHOLS spontaneously inflammable. Tetramethyl - stibonium - hy- droxide, Sb(CHo) 4 OH, is very like caustic potash. Bismuth yields tri-alkyl derivatives, e.g. Bi(CH 3 ) 3 , which are relatively unstable. No bismuthonium compounds are known. Boron tri-ethyl, B(C 2 H 5 ) 3 (Frankland), is a spontaneously inflammable liquid which burns with a green flame with deposition of much soot; and boron trimethyl, B(CH 3 ) 3 , an analogous gas of an unbearable stinking smell. The silicon compounds (Friedel and Crafts), in contradis- tinction to the foregoing, resemble methane and the paraffins rather than the spontaneously inflammable silicon hydride, and are very stable in the air. Tetramethyl silicane, Si(CH 3 ) 4 , is a mobile liquid similar to pentane, and floats on water. Tetraethyl silicane or Silico- nonane, SiEt 4 , is also known, and gives rise to numerous derivatives corresponding with those of tetraethyl methane, e.g. SiC 8 H 19 Cl, SiC 8 H 19 .O.CO-CH 3 , SiC 8 H 19 -OH, Silicononyl alcohol, &c. Compare B. 1911, 44, 2640. F. Organo-Metallie Compounds Most of the important metals form definite compounds with alkyl groups. The composition of these organo-metallic or metallo-organic compounds almost always corresponds with that of the metallic chlorides from which they are derived by the replacement of halogen by alkyl. They are colourless, mobile liquids which boil without decomposition at relatively low temperatures; they often decompose violently with water and burn explosively in the air, but in other cases they are stable, both in water and air. To the former category belong the magnesium, zinc, and aluminium alkyls, and to the latter the mercury, lead, and tin compounds. As most of the com- pour^s are volatile, their molecular weights can be deter- mined, and hence the valencies of the respective metals deter- mined, as, the alkyl radicals are monovalent. Examples are : ZnMe 2 , CdMe 2 , HgEt 2 , AlMe 3 , PbMe 4 , SnEt 4 , &c. Compounds are also known which contain halogen as well as alkyl radicals combined with a metal. They behave like salts. The halogen in them can be replaced by hydroxyl, whereby basic compounds result, compounds which are often much more strongly basic than the corresponding metallic hydroxides, in accordance with the electro-positive character O&GANO-METALLIC COMPOUNDS 119 of the alcohol radical. Such hydroxides or oxides cannot be volatilized without decomposition. Compounds of this type, e.g. CH 3 Mg-I, are very readily prepared from their com- ments (Mg + CH 3 I) in dry ethereal solution, and are ily made use of as synthetical reagents. tie organo-metallic compound may be prepared 1. By treating the alkyl haloid with the metal in question- In this way zinc-, magnesium-, and mercury-alky Is are got: = Mg(CH 3 ) 2 + MgI 2 . The mixed organo-metallic compounds (p. 121), e.g. CH 3 'Mg-I or C 2 H 5 'Zn'I, are probably formed as intermediate products. 2. Numerous metallic compounds have been prepared by double decomposition between zinc-alkyl and the metallic chloride, or more recently by the action of the mixed mag- nesium compounds on the metallic chloride. Pfeiffer (B. 1904, 37, 319, 1125, 4617) has prepared numerous tin, lead, and mercury compounds by this method: 2Zn(C 2 H 5 ) 2 +SnCl 4 = Sn(C 2 H 5 ) 4 + 2ZnCl 2 . 2C 2 H 6 .Mg.I + HgCl 2 = Hg( Potassium- and Sodium methide, K(CH 3 ) and Na(CH 3 ), and Potassium- and Sodium ethide, K(C 2 H 5 ) and Na(C 2 H 5 ), are not known in the free state. When metallic sodium is added to zinc ethyl (or ethide), zinc separates out and a crystalline compound of sodium ethide and zinc ethide is formed, from which, however, the former cannot be prepared pure, since decomposition sets in upon warming. On distilling in a stream of carbon dioxide, the potassium methide combines with the latter to form potassic .acetate; the ethyl compound behaves in a similar way. Zinc methyl or methide, Zn(CH 3 ) 2 (FranHand, 1849), is prepared according to method 1: (I) CH 3 I + Zn = Zn(CH 3 I); (H) 2Zn(CH 3 )I = Zn(CH 3 ) 2 + ZnI 2 . The first stage is completed upon warming, and the second upon distilling the resulting product. The zinc is conveniently used in the form of the "copper-zinc couple", and the reaction is facilitated by the addition of ethyl acetate, the reason for this not being known. Zinc methyl is a colourless, mobile, strongly refracting liquid of very piercing and repulsive smell. 120 IV. DERIVATIVES OF MONOHYDRIC ALCOHOLS B.-pt. 46; sp. gr. 1-39. It is spontaneously combustible, and burns with a brilliant reddish-blue flame (the zinc flame), with formation of zinc oxide, but may be distilled in an atmosphere of carbon dioxide. When the supply of oxygen is limited, zinc methoxide, Zn(OCH 3 ) 2 , is formed. It reacts violently with water, yielding methane and Zn(OH) 2 , and with methyl iodide gives ethane. It is employed in the preparation of secondary and tertiary alcohols and of ketones. Iodine con- verts it into zinc-methyl iodide, ZnCH 3 I, white plates (see above), and methyl iodide; an excess of iodine yields zinc iodide and methyl iodide. Zinc ethyl, Zn(C 2 H 5 ) 2 , b.-pt. 118, sp. gr. 1-18, closely resembles zinc methide. The mercury compounds, HgMe 2 and HgEt 2 , are produced by method of formation 1, also by method 2. They are colourless liquids of peculiar sweetish and unpleasant odour, and boil respectively at 95 and 159. They are permanent in the air, but inflammable, and both especially the methyl compound are very poisonous. Aluminium methyl, A1(CH 8 ) 3 , is spontaneously inflammable and decomposes violently with water. B.-pt. 130. For vap. dens, see B. 22, 551. Lead tetramethyl, Pb(CH 3 ) 4 , and ethyl, Pb(C 2 H 5 ) 4 (Cahours). These are formed according to method 2, curiously with separation of lead: 2PbCl 2 + 2Zn(CH 3 ) 2 = Pb(CH 3 ) 4 -f Pb + 2ZnCa,j. They are stable in the air, and are interesting from the lead in them being tetravalent. The hydroxide, Pb(CH 3 ) 3 .OH, forms pointed prisms, smells like mustard, and is a strong alkali; thus, it saponifies fats, drives out ammonia from its salts, precipitates metallic salts, &c. The compound Pb 2 (C 2 H 5 ) 6 is also known. The tin compounds are similar (Ladenburg, Frankland). Tin tetramethyl, Sn(CH 3 ) 4 , Tin tetraethyl, Sn(C 2 H 5 ) 4 , Tin triethyl, Sn 2 (C 2 H 5 ) 6 , Tin dimethyl, Sn 2 (CH 3 ) 4 , &c., are of in- terest as indicating the tetravalence of tin. For a number of years the zinc alkyl compounds were largely used for the synthesis of various groups of compounds, viz. hydrocarbons, tertiary alcohols, and ketones (see these). To a large extent these compounds are now replaced by Gri- gnard's reagents (C. 1900, 130, 1322; 1901, 132, 336, 558). V. ALDEHYDES AND KETONES 12l Any alkyl haloid, when added to dry magnesium powder sus- pended in pure anhydrous ether, yields a compound of the type CHg'Mg'I. This reaction occurs in ethyl ether, amyl ether, and in dimethylaniline, but not readily in solvents like benzene unless ether or dimethylaniline is also present. It would appear that the ether forms a definite compound, with the magnesium alkyl compound, of the type CH 8 Mg-I, (C 2 H 5 ) 2 0. Probably c 2 2 '>< 3 ( E ^ er and B. 1902, 35, 1201). These Grignard compounds in ethereal solution are extremely reactive. They have been largely made use of for the preparation of hydrocarbons; primary, secondary, and tertiary alcohols; aldehydes, acids, thio-acids, &c. (see these); also for the detection and estimation of hydroxyl groups (B. 1902, 35, 3912, and Hibbert and Sudborough, J. C. S. 1904, 85, 933) by measuring the volume of methane evolved when a given weight of the hydroxyl compound is mixed with an excess of the Grignard reagent dissolved in amyl ether. They may also be used for differentiating between primary, secondary, and tertiary amines (Sudb&rough and Hibbert, Proc. 1904, 20, 165). V. ALDEHYDES AND KETONES, CJ3J) The aldehydes and ketones are substances which are re- spectively formed by the oxidation of the primary and secondary alcohols, the oxidation consisting in the elimination of two atoms of hydrogen from each molecule of alcohol. The aldehydes are formed from the primary alcohols, and are easily converted by further oxidation into the correspond- ing acids containing an equal number of carbon atoms, oxygen being taken up. They possess in consequence strongly reduc- ing properties. The ketones result from the oxidation of the secondary alcohols, and are more difficult to oxidize further; they do not possess reducing properties. Their oxidation does not lead to acids containing an equal number of carbon atoms in the molecule, but to others containing a smaller number, the carbon chain being broken. The lower members of both classes are neutral liquids of peculiar smell, readily soluble i water and readily volatile, only CH 2 being gaseous. As the number of carbon atoms 122 V. ALDEHYDES AND KETONES increases they become less soluble, and their odour becomes less marked with rise of boiling-point until the highest mem- bers are solid, odourless like paraffin, and only capable of being distilled under reduced pressure. The aldehydes closely resemble the ketones as regards modes of formation and also in many of their properties. Both groups of compounds contain the carbonyl :C:0 group, but in the aldehydes this is always attached to a hy- drogen atom, and also to an alkyl group or a second hydrogen, e.g. CHg.CO-H and H-CO-H, whereas in a ketone it is at- tached to two alkyl groups, e.g. C 2 H 5 CO C 2 H 5 . A. Aldehydes The homologous series of the aldehydes, C n H 2n O, corre- sponds exactly with that of the acids, G^H-^f)^ They form a group of compounds exactly intermediate between the primary alcohols and the fatty acids. Each primary alcohol by the loss of hydrogen yields an aldehyde, and this by the addition of oxygen yields a fatty acid : H.CH,.OH -2H +0 / CH 3 .CH 2 -OH CH 3 .C CH 3 .C t , &c. Their boiling-points are decidedly lower than those of the corresponding alcohols, and rise, in the normal aldehydes, at first by about 27 for each CH 2 , and later on by a less amount. Nomenclature. The name aldehyde is derived from alcohol), <&%d(rogenatus), i.e. an alcohol from which hydrogen has been removed. The various aldehydes are named accord- ing to the acids to which they give rise on oxidation. For example, H-CHO formaldehyde, CH 3 CHO, acetaldehyde, &c. According to the Geneva Congress, the aldehydes receive names ending in al, e.g. ethanal for acetaldehyde. Modes of Formation. 1. By the regulated oxidation of the primary alcohols, CnH^OH, by potassium dichromate or manganese dioxide and dilute sulphuric acid; often slowly by atmospheric oxygen, especially in the presence of bone-black or platinum: ISOMERISM OF ALDEHYDES 123 2. From the acids of the acetic series, by distilling a mixture of their calcium or barium salts with calcium or barium formate (Limpricht). The foimic acid acts in this instance as a reduc- ing agent, producing calcium carbonate, thus: CHg-COOca -f- HCOOca = CH 3 .CHO + CaCOg. (ca = } Ca.) 3. From the dihalogen substitution products of the hydrotf carbons containing the group tCHX 2 , by superheating with water or by boiling with water and PbO: CH 3 .CHC1 2 + H 2 O = CH 3 .CHO + 2HCL 4. From Grignard reagents (p. 120), and ethyl formate or ethyl orthoformate. Also by heating alcohols with metals or metallic oxides (Chap. XLIX). Constitution. In the oxidation of the primary alcohols, R.CH 2 OH, to their corresponding acids, R-CO-OH, the alkyl radical R remains unaltered. It must consequently also remain unchanged in the intermediate products of the oxida- tion, viz. the aldehydes, which therefore possess the constitu- tion R-CHO: CH 3 .CH 2 -OH CH 3 .CHO CHg-CO-OH Alcohol Aldehyde Acetic acid. The aldehydes thus contain the group CHO, either -C-OH or C^TT. The former is not correct, since the aldehydes do not give the reactions characteristic of compounds containing hydroxyl radicals. All their properties point to the presence of the :C:0 group. The characteristic grouping of all alde- hydes is thus the *C^Q group. This is confirmed by the fact that an acid chloride R-C<Qj on reduction yields a primary alcohol and undoubtedly an aldehyde as an intermediate product: homers. Isomerism in the aldehydes is caused solely by isomerism in the alkyl radicals R, which are combined with the group -CHO, and 'therefore contain an atom of carbon less. Otherwise the aldehydes from C 3 H f) on are isomeric with the ketones, with the oxides of the defines (e.g. aldehyde with 124 V. ALDEHYDES AND KETONES ethylene oxide, C 2 H 4 0), and with the alcohols of the allylic series. Behaviour. The aldehydes are distinguished by being exceptionally chemically active. 1. The aldehydes are very readily oxidizable, slowly even by the air alone, and quickly by chromic acid, salts of the noble metals, &c. They consequently reduce an ammoniacal solution of silver and often one of copper; this reaction is characteristic and is especially delicate in the presence of caustic-soda solution. (Formation of silver mirror.) 2. The aldehydes are easily reduced by nascent hydrogen, e.g. sodium amalgam and dilute acid or zinc dust and glacial acetic acid, to the primary alcohols from which they are derived by oxidation, e.g.: CH 3 .CHO + 2H = CH 3 .CH 2 .OH. A glycol is formed as a by-product, e.g. butylene glycol, C 4 H 8 (OH) 2 , from C 2 H 4 O. 3. Phosphorus pentachloride and trichloride convert the aldehydes into ethylidene chloride and analogous dichloro- substitution products of the hydrocarbons: CH 3 -CHO - CH 3 .CHC1 2 . 4. Additive reactions. According to Perkin (J. C. S. 1887, 808), a solution of acetaldehyde in water contains a certain amount of the hydrate, CH 3 -CH(OH) 2 . (Cf. Chloral hydrate.) This compound is extremely unstable, and has never been iso- lated in a pure form. In those reactions in which it might be formed, its anhydride (acetaldehyde) is invariably produced, e.g. CH 3 -CHC1 9 with alkali yields CH 3 .CH:0 as final product, and not CH.uH(OH)j, although this is probably formed as an intermediate substance. Thus we conclude that two hydroxyl groups attached to the same carbon atom cannot as a rule exist together, but a molecule of water is eliminated, and an aldehyde or ketone is formed. In particular cases only can compounds with two such hy- droxyl groups exist (see Chloral). If, in place of water, NaHS0 3 , NH 3 , HCN, &c., be employed, direct addition to the aldehydes is readily observed, and in all these reactions it is concluded that the addition occurs at the expense of the doubly-united oxygen atom. A hydrogen atom of the substance in question attaches itself to the oxygen of the aldehyde, with formation of a hydroxyl group, while ADDITIVE COMPOUNDS OF ALDEHYDES 125 the residual X (e.g. NH 2 ), which was originally bound to the afore-mentioned H atom, becomes united to the carbon: CH 3 -CH: Cf. additive reactions of the defines (p. 44). The most important additive reactions are: (a) Combination with water, which would lead to a dihydric alcohol, does not as a rule take place, for the reasons already given. Should the alkyl radical of the aldehyde, however, contain several negative atoms, e.g. Cl, then the hydrates are capable of existence, for instance chloral hydrate: CC1 3 .CHO + H 2 O = CC1 3 .CH(OH)2. But even in these cases the tendency for water to separate is too great to allow of such hydrates behaving as dihydric alcohols; they react rather, for the most part, exactly like the aldehydes themselves. (Cf. Pyroracemic and Mesoxalic acids.) (b) Occasionally, compounds with alcohol or acetic acid, e.g. R.CH(OEt)(OH), or R.QH(OH)(OAc), are met with. They are, however, extremely unstable. When the aldehyde is heated with alcohol or acetic anhydride, stable ethers or esters of the hypothetical glycols are obtained : CH 3 .CHO + 2C 2 H 5 .OH = CH 3 .CH(OC 2 H 6 ) 2 + H 2 O. CH 3 .CHO + (C 2 H 3 0) 2 = CH 3 .CH(OC 2 H 3 2 ) 2 . The compounds obtained from alcohols, the so - called "acetals" (see p. 129), are also formed by the partial oxidation of primary alcohols, and are hydrolysed by sulphuric acid. (c) The aldehydes combine wit^i sodium hydrogen sulphite, NaHS0 3 , &c., to crystalline compounds, readily soluble in water but sparingly in alcohol, e.g. C 2 H 4 0, NaHS0 3 , JH 2 0. These are to be regarded as sulphite derivatives of the ethylidene glycols, for instan^, CH 8 .CH(OH)(.O.S0 2 Na). They are almost invariably decomposed when heated with alkalis or acids and regenerate the aldehydes. They are, therefore, of great importance for the separation of aldehydes from mixtures. (d) The aldehydes combine with ammonia to aldehyde- ammonias, e.g. aldehyde-ammonia, (CH 3 .CHO,NH 3 ) 3 . These are crystalline compounds, for the most part readily soluble m water, sparingly in alcohol, and insoluble in ether. Like the bisulphite compounds, they are advantageously used for the 126 V. ALDEHYDES AND KETONES purification of aldehydes, as they readily yield the aldehydes when warmed with dilute acid. (See p. 128.) (e) The aldehydes combine with hydrocyanic acid to form nitriles of higher acids; thus, acetic aldehyde yields the com- OTT pound CH 3 CH<^Q^, ethylidene cyanhydrin. This reaction is largely made use of in the preparation of certain hydroxy acids, as the cyanhydrins, when hydrolysed, yield hydroxy QTT acids, e.g. CH 8 CH<^QQQTT, lactic acid. (f) An interesting additive reaction is that between an aldehyde and a Grignard compound (p. 121). Thus acetal- dehyde and magnesium ethyl iodide yield Q j| ^>CH OMgl, 2 OFT and this with water gives methy 1-ethyl-carbinol, Q T| ^>CH OH^, (Cf. Secondary Alcohols.) 5. The aldehydes show great tendency to polymerize. (See pp. 12 and 45.) In the case of formaldehyde this poly- merization occurs spontaneously at the ordinary temperature. Acetaldehyde is polymerized upon the addition of small quan- tities of hydrochloric, sulphuric, or sulphurous acid, zinc chloride, carbonyl chloride, &c., to para-aldehyde, C 6 H 12 3 , = (C 2 H 4 0) 3 , at the ordinary temperature, and to meta-alde- hyde, (C 2 H 4 0) 3 , at 0. Why the above-mentioned substances should induce this polymerization is not known. Another type of polymerization is the aldol condensation (see pp. 127 and 131). 6. Towards alkalis the aldehydes behave differently. Alde- hyde and several of its hornologues, when heated with caustic- soda solution, are transformed into a reddish - brown resin termed aldehyde-resin, a product insoluble in water but soluble in alcohol, and possessing a peculiar odour. Other aldehydes are transformed by alkalis into a mixture of equivalent amounts of alcohol and acid, thus : 2ECOH -f H 2 = 7. The aldehydes show a great tendency to form condensation products with aldehydes, ketones, acids, &c. (See Crotonic Aldehyde, Cinnamic Acid, &c.) (a) CHo.CHO + CHo.CHO = CEL-CHiCH-CHO + H 2 O. (6) CH 3 .CO.CH 3 -f E-CHO = CH 3 .CO.CH:CHE + H 2 O. TESTS FOR ALDEHYDES 127 It is probable that in all these condensations direct addition first occurs ; for example, in (a) aldol, CH 3 CH(OH) . CH 2 CHO, is first formed, and then by the loss of- water forms croton aldehyde, CH 3 - CH : CH ; CHO. (See p. 131.) 8. With hydroxylamine the aldehydes yield the so-called Aldoximes, water being eliminated (V. Meyer , B. 15, 2778). HaiN-OH = CH 3 .CH:N.OH -fH 2 O. For the conditions under which oximes are formed, see B. 23, 2769. 9. The aldehydes react with hydrazines to form the so- called Hydrazones, water being eliminated. Phenylhydrazine is the reagent usually employed: Hg.CHiO + Ha-N.NHCA = CH 3 .CH:N.NH.C 6 H 6 + H 2 O Aldehyde-phenyl-hydrazone. Most of the phenylhydrazones are somewhat sparingly soluble in alcohol, crystallize very readily, and are made use of in identifying different aldehydes. On reduction they yield primary amines: CH 3 .CH:N.NH.C 6 H 5 -f 4H = CH 3 .CH 2 .NH 2 + NH 2 .C 6 H 6 . 10. Moist chlorine and bromine act upon the aldehydes as substituents; thus, from acetaldehyde chloral is obtained: CH 3 .CHO + 3C1 2 = CClg-.CHO + 3HGL 11. Sulphuretted hydrogen converts the aldehydes into thio- aldehydes. These are compounds of unpleasant aromatic odour, which show the same peculiarities of polymerization as the aldehydes (Klinger). (Cf. E. Baumann, B. 23, 60; 24, 1419, 3591.) Eeactions 8 and 9 may also be regarded as condensations. It is possible that in all these reactions direct addition first occurs, and that water is subsequently eliminated. Tests for aldehydes: (1) Behaviour with ammoniacal silver-nitrate solution (p. 124, and also B. 15, 1629). (2) Behaviour with alkaline bisulphites (p. 125). (3) Behaviour with phenyl - hydrazine and hydroxylamine (see above). (4) Aldehydes colour a solution of f uchsine which has been 128 V. ALDEHYDES AND KBTONES decolorized by sulphurous acid (Schi/'s reagent) an intense violet-red; some ketones and chloral, but not chloral hydrate, produce the same effect. (B. 13, 2343; Bull. Soc. Chim. 1894, 11, 692.) Formaldehyde, Methanal, HCH:0, may be regarded as the oxide of the divalent methylene radical, CH 2 :. It is obtained dissolved in water and excess of methyl alcohol by leading the vapour of the latter, mixed with air, over a glowing platinum or copper spiral or platinum asbestos (Hofmann, 1869). Other oxidizing agents lead directly to formic acid. It is a gas, condensible by cold to a clear mobile liquid, which boils at 21. A solution of about 40 per cent is an article of trade, and is known as formalin. In solution it has apparently the hydrate formula, CH 2 (OH) 2 , and is used as an antiseptic and disinfectant. Its chief polymeric forms are : (1) Para-formaldehyde, probably (CH 2 0) 2 , a white mass soluble in water; (2) trioxy-methylene, probably (CH 2 0) 8 , a crystalline compound which passes into formaldehyde again when volatilized; (3) formose (which see), a mixture of several compounds of the nature of glucose. On account of this facility for undergoing polymerization, formic aldehyde in all proba- bility plays an important part in assimilation by plants. It does not form an additive compound with ammonia, but con- denses to the complex compound C 6 H 12 N 4 , hexamethyleneamine. By its combination with hydrochloric acid, chloro -methyl alcohol (chloro -metlianol), CH 2 C1(OH), and hydroxy-chloro- methyl ether (cUoromethane-oxy-methanol), CH 2 C1 CH 2 OH, are formed. Both of these are colourless liquids, which react in many respects like formic aldehyde itself. Methylal, CH 2 (OCH 3 ) 2 (see Acetals, p. 125), is frequently made use of instead of formaldehyde, for carrying out conden- sation reactions. It is employed in medicine as a soporific, and is also used as an extractive for certain scents. B.-pt. 42. Acetaldehyde, Ethanal, Aldehyde, CH 3 CHO, was formerly termed "acetyl hydride", C 2 H 3 0H (Fourcroy and Vauquelin, 1800; composition established by LieUg in 1835). It is pre- pared by passing ammonia gas into an ethereal solution of the crude aldehyde, obtained by oxidizing alcohol with K 2 Cr 2 O r -f- H 2 S0 4 and drying over CaCl 2 , washing the precipitated aldehyde-ammonia with ether, and finally distilling it with dilute sulphuric acid. It is obtained in large quantity as a by- product in the first portions of the distillate " First Runnings " ACETAL, 'CHLORAL, ETC. 129 in the manufacture of spirit. For its production in place of vinyl alcohol, C 2 H 3 OH, from acetylene, see pp. 50 and 81. It is a colourless mobile liquid, boils at 21, and has sp. gr. about 0'8. Its odour is aromatic and suffocating, and pro- duces a kind of cramp in the chest when inhaled. It burns with a luminous flame, dissolves sulphur, phosphorus, and iodine, and is readily soluble in water, alcohol, and ether. Para-aldehyde, C 6 H ]2 3 , is a liquid sparingly soluble in water. It melts at 10, and boils at 124, i.e. more than 100 above that of aldehyde, and is used as a soporific. Meta-aldehyde, (C 2 H 4 O 3 ) 8 , crystallizes in white prisms in- soluble in water, j,nd sublimes at a little over 100, but is partially reconverted into aldehyde. (B. 14, 2271; 40, 4341.) Meta-aldehyde is changed back again into ordinary alde- hyde by prolonged heating to 115 in sealed tubes, and also, as is the case with para-aldehyde, by distillation with some- what dilute sulphuric acid. Para-aldehyde reacts in the same way as ordinary aldehyde with PC1 5 , but not with NH 3 , NaHS0 3 , AgN0 3 , and NH 2 OH. The constitution of para- aldehyde may be represented as: (KdnM and Zincke). (The union of three molecules of aldehyde by means of the valencies of carbon atoms cannot be assumed, on account of the readiness with which para-aldehyde breaks up into aldehyde.) With regard to these and other polymeric compounds, the general rule has been proved to hold that, in the case of bodies of similar constitution, the one of simpler composition is the more soluble, possesses the lower melting-point, and is the more easily vaporized. Acetal, CH 3 .CH(OC 2 H 5 ) 2 , boils at 104. It is usually ob- tained by the partial oxidation of ethyl alcohol with man- ganese dioxide and sulphuric acid, the acetaldehyde first formed condensing with the alcohol with the production of acetal. This, as well as methylal, is frequently used instead of aldehyde for the carrying out of condensation reactions (see p. 126). Propylaldehyde, C 2 H 5 .CHO, is present in wood-tar. Nor- mal heptylic aldehyde (cenanthol), C 7 H 14 0, is obtained by the dry distillation of castor-oil under diminished pressure, &c. Chloral, 2 - trichloro - ethanal, CC1 3 -CHO, is a liquid which boils at 98, and which when impure easily changes into (B480) J 130 V. ALDEHYDES AND KETONES a solid polymeric modification, meta-chloral, hut is regenerated from this upon heating. It combines readily with water to chloral hydrate, CC1 3 .CH(OH) 2 (see p. 125, a), and with alcohol to chloral alcoholate, CC1 3 . CH(OH)(OC 2 H 5 ), and tri- chloro-acetal, CC1 3 .CH(O.C 2 H 5 ) 2 . The end product of the action of chlorine upon alcohol consists chiefly of the last three substances. They are all colourless crystalline compounds, which are converted into chloral by distilling with sulphuric acid, and rectifying over lime. Chloral is an oily liquid with a sharp, characteristic odour. It combines with sodium bisulphite, ammonia, hydrocyanic acid, and acetic anhydride, and reduces an ammoniacal solution of silver oxide. It is readily oxidized to trichloracetic acid, and decomposed by alkali into chloroform and an alkali for- mate: CC1 3 -CHO + HKO = CC1 3 H -f Chloral hydrate, CC1 8 CH(OH) 2 , forms large colourless crystals readily soluble in water, melting at 57, and boiling with dissociation at 97. It acts as a soporific and antiseptic Sulphuric acid converts it into chloral. UNSATURATED ALDEHYDES Acrolein, Acrylic aldehyde, propenal, CH 2 :CH'CHO, is pro- duced by the oxidation of allyl alcohol, by the distillation of fats, and by heating glycerol with potassium hydrogen sulphate. It is a liquid boiling at 52, of pungent odour (the smell of burning fat being due to it), and of violent action upon the mucous membrane of the eyes. It unites in itself the proper- ties of an aldehyde and of an unsaturated carbon compound, and therefore combines with ammonia and with bromine; it also unites with hydrogen bromide to bromopropyl aldehyde, CH 2 Br.CH 2 .CHO. When distilled, acrolein - ammonia yields picoline, C 6 H 7 N (see Pyridine bases); and crotonic aldehyde-ammonia, by an analogous reaction, collidine, C 8 H U N. Acrolein can combine with two atoms of bromine to acrolein dibromide (dibromopropyl aldehyde), CH 2 Br CHBr CHO, a compound which is of importance in the synthesis of the sugars. (See Synthesis of Monoses.) Crotonic aldehyde, CH^CHiCH-CHO. When acetal- dehyde is left for some time in contact with dilute hydro- chloric acid or sodium hydroxide, polymerization occurs, and FORMATION OF KETONES 131 a substance termed aldol, or a-hydroxy-butyraldehyde, is obtained, CH S CH(OH) . CH 2 . CHO. The constitution of aldol follows from its properties. It cannot be readily con- verted back into acetaldehyde, and in this respect differs from the other polymeric forms, viz. meta- and para-aldehyde. This difference is due to the fact that in the aldol condensation the union of the molecules has been brought about between carbon atoms, and hence the relative stability. Aldol when distilled or in presence of dehydrating agents yields croton- aldehyde, water being eliminated. CH 3 .CH(OH).CH 2 .CHO = CH 3 .CH:CH.CHO + H 2 O. On oxidation it yields crotonic acid. B. Ketones The lowest member of the series, Acetone, contains three atoms of carbon. The higher members, from C 12 on, are solid. They are all lighter than water; e.g. the sp. gr. of acetone is 0-81 at 0. Occurrence. Acetone is present in urine, methyl-nonyl ketone in oil of rue (Ruta graveolens). Modes of Formation. 1. By the oxidation of secondary alcohols; just as in the conversion of a primary alcohol to an aldehyde, this oxidation consists in the withdrawal of two hydrogen atoms from each molecule of the alcohol: CH 3 .CH(OH).CH S + O = CH 3 .CO.CH 3 + H 2 Iiopropyl alcohol Acetone. Many primary and secondary alcohols are decomposed into hydrogen and aldehyde (or ketone) when heated in contact with a catalyst (see Chap. XLIX). 2. By the dry distillation of the calcium or barium salts of fatty acids, the metallic carbonate being also formed: Some of the ketones of high molecular weight may be ob- tained by heating fatty acids with phosphorus pentoxide (Kipping): 132 V. ALDEHYDES AND KETONES When two different acids are employed, mixed ketones, i e, ketones containing different alkyl radicals, are formed, thus : Calcium acetate and propionate Methyl-ethyl ketone. As a rule, in addition to the mixed ketone, the two simpl( ketones, e.g. (CH 8 ) 2 CO and (C 2 H 5 ) 2 CO, are also formed. 3. From dichlorides containing the group CCC1 2 C: (CH 3 ) 2 CC1 2 + H a O = (CH 3 ) 2 CO + 2HC1 Acetone chloride Acetone. It is probable that the chlorine atoms are first replaces by hydroxyls, yielding the glycol, CMe 2 (OH) 2 , which imme diately eliminates H 2 0, yielding the ketone, CMe 2 0. 4. By the action of zinc alkyl upon an acid chloride, e.g acetyl chloride, CH 3 -COC1. X)ZnCH 3 An additive compound is first formed, CH 3 C^-CH 3 Cl which must be quickly decomposed by water, otherwise ter tiary alcohols are produced: OH: = CH 3 .CO-CH 3 + HCl-f CH 3 .Zn.OH. \;Ci H; This method of formation, which was devised by Freund ii 1861, allows of the preparation of any possible ketone by usinj the requisite zinc alkyl and acid chloride. At the same time it elucidates, together with method 2, tht constitution of the ketones from the constitution of the corre spending acids. Conclusions regarding constitution based 01 the latter method must be accepted with a considerable amoun of reserve unless supported by other arguments, since in re actions which occur at high temperatures intramolecular re arrangements can readily occur. Theoretically, therefore ketones are compounds which contain the carbonyl group CO, linked on both sides with an alkyl radical, R-CO-E. I the alcohol radicals are the same, "simple" ketones result and if different, "mixed" ketones. A compound with les than 3 C atoms is thus impossible, NOMENCLATURE OF KETONES 133 Ketones have been synthesised by the action of organo- magnesium compounds on nitriles or acid amides, e.g.: x + E'H, : ^ and these with water yield R-CO-R'. (Blaise, C. 1901. 132, 38, 133, 299.) 5. From the ketonic acids or their esters, e.g. acetoacetic ester, CH 3 CO - CH 2 CO OC 2 H 5 , by warming with moderately dilute sulphuric acid or with dilute alkalis. This important re- action will be treated of at greater length under acetoacetic ester. 6. By the addition of water to homologues of acetylene, CH 3 .C:CH + H 2 = CH 3 .CO.CH 3 . This reaction occurs at relatively high temperatures, or may be brought about indirectly by the aid of sulphuric acid, or solutions of mercuric salts. homers. The ketones exhibit the same isomerism as the secondary alcohols. This isomerism depends on the one hand upon the isomerism within the alkyl groups, e.g. dipropyl ketone and di-iso-propyl ketone, which are linked together by the CO group, and on the other by the position of the oxygen atom in the carbon chain (position isomerism) ; thus, C 4 H 9 CO CH 3 is isomeric with C 3 H 7 CO C 2 H 5 . The aldehydes containing an equal number of carbon atoms in the molecule are always isomeric with the ketones, since both classes of compounds are formed from isomeric alcohols by the withdrawal of 2 H. Further, acetone is isomeric with allyl alcohol. Such an isomerism of a saturated with an unsaturated compound is termed "saturation isomerism" (cf. p. 87). Nomenclature. The usual name is formed by adding the suffix ketone to the name of the alkyl groups present; e.g. (C 2 H 5 ) 2 CO, diethyl ketone; CH 3 -CO.C 2 H 5 , methylethyl ketone, &c. The names of the simple ketones are also derived from the acids which yield them, e.g. "Valerone" (C 4 H 9 ) 2 CO, from valeric acid. The systematic names of the ketones are formed by taking the name for the corresponding hydrocarbon, adding the suffix one to indicate the O replacing "2 H, and then a number to indicate the position of the atom, e.g. CH 8 .CO.CH 2 'CH 3 , butan-2-one, &c. 134 V. ALDEHYDES AND KETONES Behaviour. 1. Reagents which give rise to nascent hydrogen reduce the ketones to secondary alcohols : (CH 3 ) 2 CO + 2 H = (CH 3 ) 2 CHOH. Small amounts of pinacones (see these) are formed. at the same time. 2. Oxidizing agents, e.g. K 2 O 2 7 , and dilute H 2 S0 4 , slowly convert the ketones into acids or ketones containing a smaller number of carbon atoms in the molecule (not as in the case of the aldehydes into acids containing an equal number), the carbon chain being broken: CH 3 .CO.CH 3 + 40 = C Since the carbon atom is tetravalent, the CO group in the ketone, being already linked to 2 alkyl radicals, can only yield the COOH group, characteristic of acids (p. 140), by the re- moval of one of the alkyl groups. In this process of oxidation of a mixed ketone the molecule usually becomes ruptured in such a manner that the CO group remains attached to the smaller alkyl group. Thus CH 3 CO: C 3 IL on oxidation yields mainly acetic CH 3 C0 2 H and propionic CoH 5 C0 2 H acids; but at the same time a small amount is oxidized to a mixture of carbonic and butyric acids (B. 25, R. 121). Since the acids formed by oxidation bear no reciprocal relation to the ketone, and the oxidation process is more complicated than in the case of the aldehydes, it is easy to understand why the ketones do not possess reducing pro- perties. 3. Phosphorus pentachloride, PC1 5 , converts the ketones into the corresponding dichlorides, acetone, for instance, into acetone chloride, (CH 3 ) 2 CC1 2 . 4. Additive reactions, (a) The ketones do not as a rule combine with water and alcohol, for the reasons given under the aldehydes and at p. 132. (b) With ammonia they yield complex condensation pro- ducts, e.g. di - acetone - amine, C 6 H 13 NO, tri - acetone - amine, CgH^NO (Heintz) ; this reaction is more complicated than that with the aldehydes, 2 or 3 molecules of acetone combining with 1 molecule of ammonia, with elimination of water. (c) The ketones which contain the group CH 8 CO, and a few other relatively simple ketones, combine with sodium hydrogen sulphite to crystalline compounds, e.g. acetone tc (CH 8 ) 2 C<\Q OQ -AT , H 2 0, which can be converted back intc the ketone by distillation with sodium-carbonate solution. This REACTIONS OF KETONES 136 very important reaction is made use of in separating and puri- fying the ketones. Stewart has recently (J. C. S. 1905, 87, 185) studied the comparative rates at which some of these compounds are formed. (d) With hydrocyanic acid they yield hydroxy-nitriles, as in the case of the aldehydes; e.g. (GE^fk^- (e) Ketones readily form additive compounds with Grignartfs reagents, and when decomposed with water these yield tertiary alcohols (see p. 72) : Me 2 CO + MeMgI H = Me 3 C.OH + OH-Mg-I. 5. The ketones, unlike the aldehydes, do not possess the property of polymerizing, but they form condensation products. Just as aldehyde is converted into crotonic aldehyde, so is acetone, by the action of many reagents e.g. CaO, KOH, HC1, and H 2 S0 4 converted, with elimination of water, into mesityl oxide, C 6 H 10 0, phorone, C 9 H U 0, or mesitylene, C 9 H 12 , accord- ing to the conditions (see these substances): 203^0 = C 6 H 10 + H 2 O. . 3C 3 H 6 = C 9 H U O -}- 2H 2 O. 3C 3 H 6 O = C 9 H 12 + 3H 2 O. Analogous condensations also ensue with other ketones or aldehydes under the influence of dilute caustic soda or of sodium ethoxide (B. 20, 655). In this way the more compli- cated ketones are formed (A. 218, 121). 6. Sulphuretted hydrogen converts the ketones into thio- compounds, e.g. acetone into thio-acetone, CH 3 -CS'CH 3 (B. 16, 1368), or their polymers. 7. Halogens give rise to substitution products. 8. Like the aldehydes, the ketones even C 35 react with hydroxylamine, yielding oximes, which are termed Ketoximes (V. Meyer, B. 15, 1324, 2778; 16, 823, 1784, &c.): (CH 3 ) 2 C : p+'H 2 ;N.OH = H 2 O + (CH 3 ) 2 C:N.OH(acetoxime). 9. They react in an analogous manner with phenyl-hydrazine, C 6 H 5 .NH.NH 2 (E. Fischer, B. 17, 572), with the formation of phenyl-hydrazones (p. 127): (CH 3 > 2 C:N.NH.C 6 H 6 + H 8 0. Aceton e-phenyl-hy drazone. 136 V. ALDEHYDES AND KETONES Phenyl-hydrazine and hydroxylamine are therefore of great value for the recognition of the aldehydic or ketonic character of a substance. Semicarbazide, NH 2 .CO-NHNH 2 , reacts in an analogous manner (A. 1898, 303/79), and it or its hydro- chloride is now largely used as a reagent for aldehydes and ketones, as the products (semicarbazones) crystallize well and have definite melting-points: (CH 3 ) 2 CO + NH 2 .NH.(X).NH 2 = H 2 + (CH 3 ) 2 C : N NH CO NH 2 . Acetaldehyde-semicarbazone melts at 162, and acetone-semi carbazone at 187. 10. Nitrous acid (ethyl nitrite and sodium ethylate) gives rise to iso-nitroso-ketones, e.g. iso-nitroso-acetone, CH 3 -CO' CH:NOH, by replacement of H 2 by the group :N*OH (oximino). When hydrolysed, the :NOH group is replaced by oxygen, and diketones or aldehydo-ketones are formed. Acetone, 2-Propanone, CH 3 COCH 3 . The formula was established by Liebig and Dumas in 1832. It is present in very small quantity in normal urine, in the blood, in serum, &c., but in much larger quantity in pathological cases such as acetonuria and diabetes mellitus. It is produced, among other ways, by the distillation of sugar, gum, cellulose, &c., and is therefore present in wood spirit; also by the addition of water oo allylene, C 3 H 4 (p. 50). On the large scale it is prepared by the dry distillation of calcium acetate. It is a liquid of peculiar pungent odour j boils at 56, and has sp. gr. 0*81 at 0. It is soluble in water, but may be salted out from its aqueous solution, and is also miscible with alcohol and ether. KMn0 4 does not oxidize it in the cold, but Cr0 3 converts it into acetic and carbonic acids. Metallic sodium reacts with acetone, yielding the derivative CH 8 .C(ONa):CH 2 . Detection. Acetone may be detected by the formation of indigo when its solution in sodium hydroxide is warmed with o-nitro-benzaldehyde. Sulphonal, (CH 3 ) 2 : C(S0 2 C 2 H 5 ) 2 , is formed when a mixture of acetone and mercaptan is treated with hydrochloric acid, and the mercaptol, (CH 3 ) 2 C(SC 2 H 5 ) 2 [a derivative of the hypothetical acetone-glycol, (CH 3 ) 2 C(OH) 2 ], which is thus formed, is oxidized by potassium permanganate to the corre- sponding sulphone. It crystallizes in prisms, melts at 125 and acts as a soporific. ALDOXIMES AND KETOXIMES 137 Mesityl oxide, C 6 H 10 0, = CH 3 . CO OH : C(CH 3 ). 2 (Kane, 1838; Baeyer), is a liquid of aromatic odour, boiling at 132. Phorone, C 9 H 14 0, = (CH 3 ) 2 C : CH . CO . CH : C(CH 3 ) 2 , forms readily fusible yellow crystals. Both of these compounds are obtained by saturating acetone with hydrochloric acid gas (A. 180, 1). Methyl ethyl ketone (2-Butanone), CH 3 CO'C 2 H 5 , is present in crude wood spirit, and is also formed by the oxidation of secondary butyl alcohol. B.-pt. 81. Pinacoline (2-Dimethyl-3-bufanone), methyl tertiary-butyl ketone, CH 3 CO C(CH 3 ) 3 , is produced by the action of dilute sulphuric acid upon pinacone (p. 193). This involves a characteristic rearrangement known as the "pinacoline reaction". B.-pt. 106. A number of ketones have been obtained from the higher fatty acids. These have been converted by Krafft into the corresponding paraffins, by first transforming them into the chlorides, C n H 2n Cl 2 , by means of PC1 5 , and then heating the latter with hydriodic acid and phosphorus. ALDOXIMES AND KETOXIMES The aldoximes and ketoximes are the compounds obtained by the action of hydroxylamine on the aldehydes and ketones respectively. They both contain the bivalent oximino group ; N OH attached to carbon, e.g. : CH 3 .CH:N.OH and (CH 3 ) 2 C:N.OH Acetaldoxime Acetoxime. They are either colourless crystalline compounds or liquids, and are both basic and acidic in properties. With metallic hydroxides they yield salts of the type CH 3 -CH:NOK; with mineral acids they form salts in much the same manner as ammonia does, e.g. CMe 2 :NOH, HC1. The oximes are fairly readily hydrolysed by dilute acidjs, yielding hydroxylamine and either an aldehyde or a ketone. On reduction they all yield primary amines, :N OH-*NH 2 . Dehydrating agents, e.g. acetic anhydride or acetyl chloride, transform the aldoximes into nitriles, water being eliminated: GH 8 .C;H;:Nv()BG = CH 3 .C:N + H 2 O. The ketoximes with acetyl chloride undergo an interesting intramolecular rearrangement known as the Bedcmann transfor- mation, the final product being an acid amide or anilide. It 138 V. ALDEHYDES AND KETONES is probable that the hydroxyl group of the oxime changes place with one of the alkyl groups attached to the carbon atom, and this then leads to a wandering of a hydrogen atom and a shifting of the double bond: R-C-R' E.G. OH K.C:O N.OH " N.R' NHR'. Constitution. In the formation of the oximes the water eliminated is undoubtedly formed from the oxygen of the carbonyl group and the hydrogen atoms of the hydroxylamine, otherwise the reaction would be of the type H 2 O, and an aminoketone would result. There are two possible* ways in which water can be thus eliminated, yielding a com pound CMe 2 :NOH or CMe 2 <J . That the first of these two formulae is correct is demonstrated b the fact that when an alkyl derivative, :C:NOR or :C\ | , is hydrolysed X N-R with hydrochloric acid an alkyl derivative of hydroxylamine, NH 2 'OR, is obtained, and hence the alkyl group is presum- ably attached to oxygen in the alkylated oxime, and the oxime itself thus contains an OH group. This constitution formula is in perfect harmony with the reactions character- istic of oximes. The oxime derived from an aldehyde or ketone often exists in isomeric forms. This is especially true of those derived from aromatic aldehydes and from mixed (unsymmetrical) ketones of the aromatic series. According to Goldschmidt and V. Meyer, these isomers are structurally identical, and are stereo-isomeric (i.e. the isomerism is due to the spatial relationship of the various atoms and radicals). According to Hantzsch and Werner, the isomerism is readily explicable if we assume that two of the three valencies of the nitrogen atom, when N is united by a double bond to C, lie in the same plane, but that the third valency lies outside this plane. Thus R.C.H N SATURATED MONOBASIC ACIDS 139 with the oxime derived from an aldehyde, if the two valencies attaching N to C lie in a plane at right angles to the plane of the paper, then the OH radical must fall either close to the alkyl group R or to the H atom; in fact, two configurations are possible, viz. : R.C.H B-C.H N.OH HO.N. These are known (1) as sy?i-aldoximes when the H and OH are close together, and as a rule they readily lose water, yielding nitriles; (2) as anti-aldoximes when the H and OH are far removed from one another. As a rule, these yield acetyl derivatives, and not nitriles, on treatment with acetyl chloride. The oximes derived from unsymmetrical ketones also often exist in stereo-isomeric forms, which can be explained in a similar manner: R-C-R' R-C-R' N.OH HO-N. No isomerism should occur, and so far none has been met with, in the case of the oxime derived from a symmetrical ketone when R = R'. The configurations of these isomeric ketoximes are generally derived from a study of the Beckmann transformation. R.C-R' R.C-R' gives R CO NHR' and || gives NHR CO R N-OH OH-N (See also Aromatic Aid oximes and Ketoximes.) VI. MONOBASIC FATTY ACIDS A. Saturated Acids, C.H.A, or CJWCO.H (See Table, p. 140.) The monobasic fatty acids are formed by the oxidation of the saturated primary alcohols or of their corresponding aldehydes. These acids are monobasic, i.e. contain in the 140 VI. MONOBASIC FATTY ACIDS molecule only one replaceable atom of hydrogen, since, as a rule, they give rise to only one series of salts or of esters. They are known as the fatty acids, because many of them are contained in fats or are formed from fats by processes of oxidation or hydrolysis. They are often spoken of as acids of the aliphatic series. The characteristic group of the monobasic acids is the carboxylic group 'C^Q TTJ and it is the hydrogen of this group which becomes replaced in the formation of salts. The basicity of an acid, as a rule, depends on the number of such carboxylic groups present in the molecule. NORMAL FATTY ACIDS AND THEIR PHYSICAL DATA i-COgH, where C^H^+i is a normal alkyl group. Mclting-pt. Boiling-pt. CHnO. 8'3 101 Acetic acid. C 9 H,O 17 118 Propionic acid CoH.O, 36 141 Butyric acid C 4 H 8 O 2 8 162 Valeric acid . . aH, n o 9 186 Caproic acid CH + 8 205 Heptoic acid CH 10 224 Caprylic acid CcH ir O, -1- 16 236 CH 12 254 r TT r? 31 269 TJndecylic acid C^HgoOo 28 -{213 Laurie acid C 19 H 9d O 2 - 43 {226 Tridecylic acid C H 40 236 Mrristic acid . 54 248 Pentadecylic acid 51 257 Palmitic acid 63 (269 Margaric acid p ic S 32 2 2 60 1277 Stearic acid 69 {287 Nondecylic acid C,oHooOo 66 {298 A rachidic acid p TT n 75 C H 83 Lignoceric acid cXA 80 78 Melissic acid C*HO! 90 The lower members of the series are liquids of pungent FORMATION OF FATTY ACIDS 111 odour and corrosive action, and boil without decomposition. They dissolve readily in water, and the aqueous solutions exhibit a strongly acid reaction, although most of the anhydrous acids are without action on dry litmus paper. The intermediate members have an unpleasant smell like that of rancid butter or perspiration, and are oily and but slightly soluble in water. Mobility, odour, and solubility diminish as the percentage of carbon increases. The higher members, from C 10 , are solids, like paraffin, insoluble in water, and can only be distilled without decomposition in a vacuum. Their acid character no longer finds expression in their reaction with litmus, but in their capability of forming salts with bases. These higher acids are readily soluble in alcohol, and especially in ether. In this series the boiling-point rises regularly for each increase in the number of atoms in the molecule. The rise is roughly 19 for each increment of CH 2 . The melting- points do not exhibit the same regularity: the melting-point of any acid containing an even number of C atoms in the mole- cule is higher than the melting-point of the acid with an odd number of C atoms which immediately succeeds it. Similar phenomena have been observed in other homologous series. (See section on Physical Properties and Constitu- tion.) The specific gravity of the liquid acids is at first > 1, and from C 3 onwards < 1, and it decreases continuously to about 0'8, the paraffin character of the hydrocarbon radical becoming preponderant. Occurrence. Many of the acids of this series are found in nature in the free state, but more frequently as esters, viz. : (a) esters of monohydric alcohols (see wax varieties), (b) esters of glycerol or glycerides, in most of the vegetable and animal fats and oils. For further particulars see pp. 157 and 158. Formation. 1. By the oxidation of the primary alcohols, R.CH 2 .OH, or their aldehydes, R.C<Q, by means of K 2 Cr 2 O r or Mn0 2 and dilute H 2 S0 4 , or by the oxygen of the air in presence of platinum or of nitrogenous substances, e.g. acetic acid from alcohol. The acids thus formed contain the same number of carbon atoms as the alcohol or aldehyde. Many complex carbon compounds, e.g. ketones, unsaturated compounds, &c., when oxidized yield acids containing a smaller number of carbon atoms. The higher acids of this series are converted into their lower homologues when oxidized. 142 VI. MONOBASIC FATTY ACIDS 2. Several acids have been prepared from the halogen com- pounds containing the group CX 8 , e.g. : HCC1 3 + 4KOH = H-COaK + 3KC1 + 2H 2 O. We should expect an exchange of the three chlorine atoms for three hydroxyls, with formation of the intermediate com- pounds CH(OH) 3 or RC(OH) 8 . Such compounds are, how- ever, extremely unstable, and immediately eliminate water, yielding the acids (cf. p. 124): OH :H = But derivatives of these trihydric alcohols, or ortho-acids as they are termed, are known; for example, ethyl ortho-formate, HC(OC 2 H5) 3 , a neutral liquid of aromatic odour, insoluble in water, and boiling at 146. 3. From the alkyl cyanides or nitriles, (^EL^CN. The cyanides, which are prepared by warming the alkyl iodides with cyanide of potassium, are converted into the fatty acids and ammonia by hydrolysis with potassium hydroxide solu- tion, with dilute or concentrated hydrochloric acid, or with sulphuric acid diluted with its own volume of water. The reaction may be regarded as the addition of two mole- cules of water to each molecule of nitrile : CH S .C:N CH S .(X).NH 2 CHa-CO-ONE^ + H 2 +H,0 first yielding the acid amide, and then the ammonium salt of the acid, which is decomposed by the hydrolysing agent employed. The process, in the case of aromatic nitriles, can be stopped at the point when the acid amide is formed, but in the aliphatic series this is almost impracticable. The reaction is the exact reverse of the formation of nitriles from the ammonium salts of fatty acids: CH 3 .CO-ONH 4 CH 3 .CO-NH 2 CH 3 .C:N. -H 2 -H 2 O The great importance of this reaction, by means of which we can obtain an acid C n+1 from an alcohol C n , has been already indicated (p. 101). And since the acids can be con- verted indirectly by reduction into the corresponding alcohols, FORMATION OF FATTY ACIDS 143 it is thus possible to build up synthetically, step by step, the alcohols richer in carbon from those poorer in carbon, a cir- cumstance which is of especial importance in the case of the normal alcohols (Lieben and Eossi). As an example: qa 3 .OH CH 3 I CH 3 .CN CHg-COOH CHg-CHO P and I KCN Hydrolysis With calcium formate CH 3 .QH 2 OH Reduction. 4. The acids may be regarded as resulting from the par- affins, e.g. acetic acid from CH 4 and C0 2 , and formic acid from H 2 and C0 2 . The two components can be made to combine indirectly; thus, carbon dioxide and sodium methyl (p. 119) combine when heated together (Wanklyn)-. CH 3 Na + C0 2 = CH 3 .C0 2 Na. Formic acid is obtained in an analogous manner from hydrogen and carbon dioxide, under the influence of the silent electric discharge: H 2 + CO, = H.C0 2 H; or from hydrogen, potassium, and carbon dioxide, when the potassium is placed in a bell-jar filled with moist carbon dioxide (Kolbe and Schmitt, 1861); or by treating carbonate of am- monia, &c., with sodium amalgam. 5. By passing carbon monoxide over heated caustic alkali or alcoholate, thus: CH 3 -ONa -f CO = CH 3 -C0 2 Na (at 160). H-ONa + CO = H.C0 2 Na. 6. By the action of carbon dioxide on ethereal solutions of organo-magnesium haloids, a magnesium compound, C n H 2n+1 .Mg.I is obtained, which gives the free acid on the addition of dilute sulphuric acid (C. 1904, 138, 1048). 7. By the addition of hydrogen to unsaturated acids, e.g. propionic acid, CH 3 -CH 2 .C0 2 H, from acrylic acid, CH 2 :CH- C0 2 H. This addition of "hydrogen may be effected (a) directly by hydriodic acid and phosphorus, sodium amalgam and water, or by the aid of hydrogen and reduced nickel at a temperature of about 100 (Abstr. 1903, 1, 547), or hydrogen and colloidal 144 VI. MONOBASIC FATTY ACIDS palladium at the ordinary temperature, Chap. XLIX; (b) in- directly, by addition of hydrobromic acid and inverse substi- tution. Unsaturated acids also yield saturated ones contain- ing fewer carbon atoms when fused with potash, e.g. 1 mol. crotonic acid, C,H 6 2 , yields 2 mols. acetic acid, C 2 H 4 2 . 8. From the nydroxy acids, by reduction with hydriodic acid: CH 3 .CH(OH).C0 2 H + 2HI = CH 3 .CH 2 .CO 2 H + I 2 -f H 2 O Lactic acid Propionic acid. 9. From many polybasic acids, by the elimination of C0 2 , for example, formic from oxalic, COOH;COOH, and acetic from malonic, iC0 2 ;H CH 2 C0 2 H. 10. Aceto-acetic ester syntheses. The homologues R.CH 2 .COOH and can be prepared from acetic acid by first converting the latter into aceto-acetic ester, CH 3 CO CH 2 COOC 2 H 5 , introducing alkyl groups into this, and then decomposing the compound so obtained by concentrated alcoholic potash. (Cf. Aceto- acetic Ester, p. 228; and Malonic Ester, p. 238.) Separation. Natural fats are nearly all glycerides, i.e. esters derived from the trihydric alcohol, glycerol, and various fatty and other acids, so that a mixture of acids is obtained when any natural fat is hydrolysed. This mixture may be separated into its components as follows : (a) By fractional distillation in a good vacuum; (b) by fractional precipitation of an alcoholic solution of the acids by means of magnesium acetate, calcium chloride, &c., the acids richer in carbon being precipitated first; (c) by frac- tional solution: the dry barium salts of formic, acetic, pro- pionic, and butyric acids are very differently soluble in alco- hol, the solubility increasing rapidly with the number of carbon atoms; (d) by fractional neutralization, and distillation of the non-combined acid. Behaviour. 1. Salts. The acids are monobasic, and thus form normal salts, e.g. CHgC0. 2 Na. They also yield acid salts the so-called per-acid salts from the existence of which we might feel inclined to doubt their monobasic nature. These salts can, however, be crystallized from a strongly acid solution only; they decompose on the addition of water, and a]so lose their excess of acid when heated. The formation of CONSTITUTION OF FATTY ACIDS 145 such acid salts is now usually regarded as being due to the tetravalency of one of the oxygen atoms, e.g. : All the other chemical characteristics of the acids go to prove their monobasicity, especially the non-formation of acid esters. 2. The monobasic acids give rise to different groups of deri- vatives in much the same manner as the monohydric alcohols. The typical hydrogen atom is replaceable by an alkyl group with formation of an ester or alkyl salt, e.g. CH 3 CO OC 2 H 5 , ethyl acetate, or by a second acid radical with formation of an anhydride ; the hydroxyl may further be replaced by halogen, especially chlorine, to an acid chloride, by SH to a thio-aeid, by NH 2 to an amide, &c. (See Acid Derivatives, p. 171.) 3. Halogens act upon the acids as substituents (see p. 167). 4. When the alkali salts are heated with soda lime, or fre- quently when the silver salts are heated alone, carbon dioxide is eliminated and*a paraffin formed (see e.g. Methane). Paraffins are also formed when the alkali salts are electrolysed (see Ethane). 5. Most of the acids are relatively stable towards oxidizing agents, formic acid alone being readily oxidized to carbonic acid, and thus possessing strong reducing properties. 6. When the lime salts of the acids are heated with calcium formate they are reduced to aldehydes, and when heated for a lengthened period with hydriodic acid and phosphorus, tc paraffins. Qa. When the lime salts are distilled alone, or are heated with phosphorus pentoxide, they are transformed into the ketones, (C n _ 1 H 2n _ 1 ) 2 CO. Constitution. It follows from their modes of formation, especially 3, 4, and 6, and also from their behaviour (see 4 above), that acetic acid and its higher homologues contain alkyl radicals. The conversion of the alcohols into acids containing 1 atom of carbon more, by means of the cyanides, is especially strong proof of this. The latter contain the alkyl radical bound to the nitrile group CiN, and when they are hydrolysed the alkyl radical remains unchanged, and the tervalent nitrogen is replaced by 0" and (OH)', both of these attaching themselves to the carbon atom of the original cyanogen, and so forming the group (B480) 146 VI. MONOBASIC FATTY ACIDS Consequently all the oxygen in the acid is united to a single carbon atom in the form of the group C0 2 H. This group, which is termed carboxyl, is characteristic of the existence of acid properties. Further proof of the presence of the carboxyl group is based largely on the reactions of the acids. The alkyl group which they contain must be directly attached to C, as it is not removed by the action of acids or alkalis. We thus have C n H ?n+1 C. The presence of an OH group follows from the reaction of the acids with PC1 3 or PC1 5 , when an atom of and an atom of H become replaced by an atom of Cl, and they must presumably therefore be present in the form of the univalent 0H group. There is only 1 oxy- gen atom left over to account for, and this is presumably attached to the C by a double bond, and thus we have The monobasic acids may therefore be re- garded as compounds of the alkyl radicals with carboxyl, or, in other words, as derived from paraffins by the replacement of one hydrogen atom by a carboxyl group, thus : Formic acid is, in this way, the hydrogen compound of carboxyl, H-COoH. The acids are distinguished as primary, secondary, or tertiary, according as the alkyl radicals which they contain are pri- mary, &c. Thus: Primary Secondary Tertiary E-CH 2 .CO 2 H EE'CH.C0 2 H EE'E"C-C0 2 H. There is no room for doubt that it is the hydrogen atom of the carboxyl group, the so-called "typical" hydrogen atom, which is replaced by metals in the formation of salts, for the foregoing acids are all monobasic, and consequently the number of hydrogen atoms present in the alkyl radical is of no moment for the acid character. In the di- and polybasic acids, the presence of two or more carboxyls can usually be demonstrated. If the composition of the primary alcohols, E-CH 2 'OH, is compared with that of the corresponding acids, E-COOH (E = alkyl or hydrogen), the latter are seen to be derived from the former by the exchange of two atoms of hydrogen for one atom of oxygen] The character of the original FORMIC ACID 147 substance is thus completely changed by the entrance of the electro- negative (acidifying) oxygen. Nomenclature. The names for the first five acids are special; from C 6 onwards, with a few exceptions, the names for the normal acids indicate the number of carbon atoms, e.g. hexoic, heptoic, or heptylic, &c. The systematic name (Geneva Con- gress) of the normal compound is obtained by adding the word acid to the name of the paraffin containing the same number of carbon atoms, e.g. acetic acid = ethane acid. The monovalent radicals left when OH is removed from the molecule of each acid are often spoken of as acid or acyl radicals. (Cf. Alkyl Eadicals.) The commonest of these radicals are CH 3 CO., acetyl; C 2 H 5 CO., propionyl; C 3 H r .CO., butyryl; &c. The aldehydes may be looked upon as hydrogen compounds of the acyl radicals, and the ketones as compounds of the latter with alkyl radicals, thus : (CH 3 .CO)H (aldehyde) (CH 3 .CO)CH 3 (acetone). The constitution of aldehydes and ketones, and of compounds derived from them, is based on the constitution of the mono- basic acids. homers. The acids of the acetic series show the same iso- merism as the alcohols containing 1 atom of carbon less, since they are formed from these by means of the cyanides. Thus we have 1 propionic acid, 2 butyric acids corresponding with the 2 propyl alcohols, 4 valeric acids corresponding with the 4 butyl alcohols, and so on. Formic acid (Methane acid), acidum formidcum, CH 2 2 (Samuel Fisher and John Wray, 1670; Marggraf), occurs free in ants, especially Formica rufa, in the processionary cater- pillar (Bombyx processionea), in the bristles of the stinging nettle, the fruit of the soap-tree (Sapindus saponaria), and in tamarinds and fir cones; also in small quantity in various organic liquids, in perspiration, urine, and the juice of flesh. Formation. From HCN, CHClg, CH 3 OH, C0 2 , &c. (See General Methods of Formation.) Its salts are obtained by the reducing action of sodium amalgam upon ammonium carbonate or solutions of the alkali hydrogen carbonates (Lieben); the free acid by the dry distillation or oxidation of many organic substances, e.g. starch (Scheele). Preparation. 1. Sodium formate is obtained by absorbing carbon monoxide in soda lime at 210 (Merz). 148 VI. MONOBASIC FATTY ACIDS 2. When oxalic acid is heated, formic acid is obtained in small quantity together with carbon monoxide, carbon dioxide, and water, and the same effect is produced by the direct action of sunlight upon its aqueous solution containing uranic oxide : C 2 H 2 4 = CO 2 + CH 2 O 2 . This decomposition is best effected by heating crystallized oxalic acid with glycerol to 100-110 (Berthelot, Loriri), the formic acid produced combining with the glycerol to an ester, monoformin (see Glyceryl Esters) : CH 2 .OH CH 2 .OH CH.OH = CH-OH -f H 2 O. This remains behind in the flask, and practically only water and carbon dioxide pass over. The monoformin is then hy- drolysed either by boiling it with excess of water or by the addition of more oxalic acid, the water of crystallization of the latter acting as the hydrolysing agent. The formic acid distils over with the water, and then the anhydrous oxalic reacts again with the glycerol, yielding monoformin and carbon dioxide, the process repeating itself time after time, a very small amount of glycerol being thus sufficient to convert considerable quantities of oxalic into formic acid. (B. 15, 928.) The anhydrous acid is obtained by decompos- ing the solid lead or copper salt with sulphuretted hydrogen. Properties. It is a colourless liquid which solidifies in the cold and fumes slightly in the air. M.-pt. +9; b.-pt. 101; sp. gr. .1*22. It has a pungent acid and ant-like odour, acts as a powerful corrosive, and produces sores on the soft parts of the skin. It is a much stronger acid than acetic acid, is a powerful antiseptic, and decomposes completely into carbon monoxide and water when heated with concentrated sulphuric acid: CH 2 2 = CO + H 2 0. Salts. Potassium-, HC0 2 K, sodium-, HC0 2 Na, and am- monium formate, HC0 2 NH 4 , form deliquescent crystals. The first two yield oxalates when strongly heated, with evolution of hydrogen (see Oxalates); the ammonium salt yields form- amide and water at 180: HC0 2 .NH 4 = H.C ACETIC ACID 149 The lead salt, Pb(HC0 2 ) 2 , forms glistening, sparingly soluble needles, the copper salt, Cu(HC0 2 ) 2 + 4H 2 0, large blue mono- clinic crystals, and _the silver salt colourless crystals. The last-mentioned deposits silver when warmed, consequently a solution of nitrate of silver is reduced when heated with formic acid. A solution of the soluble mercuric salt, Hg(HC0 2 ) 2 , evolves carbon dioxide when gently warmed, and yields free formic acid together with the sparingly soluble mercurous salt, Hg 2 (HC0 2 ) 2 , which separates in white plates; on further heating, carbon dioxide, formic acid, and metallic mercury are obtained. Similarly an aqueous solution of mercuric chloride is reduced by formic acid to the mercurous salt, Hg 2 Cl 2 . Formic acid is thus a strong reducing agent, and in this respect differs from the other members of the series : HCO-OH == C0 2 + 2H. It decomposes into carbonic acid and hydrogen when heated alone to 160, or when brought into contact with finely-divided rhodium. This power of reduction may be attributed to the alde- hydic grouping contained in its constitutional formula, H-O-CHrO. Acetic acid (Ethane add), CH 3 COOH, was known in the dilute form, as crude wine vinegar, to the ancients. Stahl prepared the concentrated acid about 1700. Glauber mentions wood vinegar (1648). Its constitution was established by Berzelius in 1814. Salts of acetic acid are found in various plant juices, especially those of trees, and in the perspiration, milk, muscles, and excrementa of animals. Esters of acetic acid also occur, e.g. triacetin in cro ton-oil (see p. 158, and also under Grlycerol). Formation (see p. 140 et seq.).It, is the final product of the oxidation of a great many compounds, and also of their treat- ment with alkalis. The following synthesis is of historical interest: Perchloro- ethylene, C 2 C1 4 , which is prepared from CC1 4 , i.e. from Cl and CS 2 , yields with chlorine in presence of water in direct sun- light trichloracetic acid, carbon hexachloride, C 2 C1 6 , being obviously formed as intermediate product (Kolbe, 1843): = CC1 3 .C0 2 H 150 VI. MONOBASIC FATTY ACIDS The latter acid is reduced to acetic by nascent hydrogen (Melsens). Preparation. 1. From alcohol. A dilute aqueous solution of alcohol, containing up to 15 per cent, is slowly converted into acetic acid on exposure to the oxidizing action of the air and in presence of certain low forms of plant life known as bacteria, especially Bacterium aceti. These organisms are con- tained in the air, and hence become deposited in alcoholic liquors exposed to the air, and thus produce the souring of wines, &c. For the growth of the micro-organisms it is essential that nitrogenous matter, phosphates, &c., shall be present, and hence pure alcohol mixed with water does not turn sour. In the "quick process" dilute alcoholic liquors are allowed to trickle over beechwood shavings which have been previously coated with the required bacteria (mother of vinegar), and the temperature is kept at about 35. Vinegar is an aqueous solution of acetic acid, usually con- taining only 3 to 5 per cent, but containing also small quan- tities of alcohol, of the higher acids, e.g. tartaric and succinic, the ethyl esters of the acids, albuminoid matters, &c. 2. From wood. The dry distillation of wood, which is con- ducted in cast-iron retorts, yields: (1) gases, e.g. hydrogen 15 per cent, methane 11 per cent, carbon dioxide 26 per cent, carbon monoxide 41 per cent, and higher hydrocarbons 7 per cent; (2) an aqueous solution known as pyroligneous acid, which, in addition to acetic acid, contains methyl alcohol, acetone, homologues of acetic acid, and strongly smelling combustible products (empyreuma); and (3) wood-tar, which contains compounds of the nature of carbolic acid. The pyroligneous acid is worked up for acetic acid by converting it into the sodium or calcium salt, heating these the former up to its melting-point and the latter to 200 to get rid of empyreu- matic substances, and then distilling with sulphuric acid. Properties. Acetic acid is a strongly acid liquid of pungent odour, which feels slippery to the touch and burns the skin, and which solidifies on a cold day to large crystalline plates melting at 17; (glacial acetic acid). It boils at 118, and its vapour burns with a blue flame; sp. gr. at 15, 1*055. When mixed with water, contraction and consequent increase in den- sity ensue, the maximum point corresponding with the hydrate CH 3 .C0 2 H -f H 2 0, = CH 3 -C(OH) 3 (ortho-acetic acid), which contains 77 per cent acid and has a sp. gr. of 1'075 at 15*5; after this, the specific gravity decreases with further addition ACETATES 161 of water, so that a 50-per-cent acid has almost the same density as one of 100 per cent. The amount of acid present in a solu- tion is determined either by its sp. gr., this contraction being borne in mind, or by titration with standard alkali, using phenolphthalein as indicator, or with very concentrated acid by a careful determination of its melting- (freezing-) point in the Beckmann apparatus. The vapour density near the boiling- point is much higher than that required by theory, but is normal above 250. The high values are due to the associa- tion of the molecules at the lower temperatures, and in the liquid state the molecular formula is undoubtedly (C 2 H 4 2 ) X , &c. The acid is hygroscopic, and stable towards chromic acid and cold permanganate of potash. It dissolves phosphorus, sulphur, and many organic compounds, is corrosive, and gives rise to painful wounds on tender parts of the skin. Salts. All the normal acetates are soluble in water. The following potassic salts are known : (a) KC 2 H 3 2 , (b) KC 2 H S 2 , HC 2 H 3 2 , and (c) KC 2 H 3 O 2 , 2 HC 2 H 3 2 . Sodium acetate, CH 3 COONa, 3 H 2 0, forms transparent readily soluble rhombic prisms. Ammonium acetate, CH 3 - CO ONH 4 , resembles the potassium salt. It is used in medi- cine as a sudorific (liquor ammonii acetici). Its solution loses ammonia on evaporation, and it yields acetamide when dis- tilled. Ferrous acetate, Fe(C 2 H 3 2 ) 2 , is largely used in the form of " iron liquor " as a mordant in dyeing. The normal ferric salt, Fe (C 2 H 3 2 ) 3 , which is employed for the same pur- pose, is obtained when a soluble ferric salt is mixed with sodium acetate. Its solution is deep red in colour, and deposits the iron as basic salt, CH 3 CO OFe(OH) 2 , when heated with excess of water. It is used in medicine as "liquor ferri acetici". The analogous aluminic acetate is known only in solution, and finds a wide application as " red liquor " mordant in calico printing and dyeing. Its use depends upon the fact that it is readily hydrolysed by water, e.g. when exposed to the action of steam, and on the insolubility of the compound (lake) formed from the residual alumina and the colouring matter. It is employed in small doses as an astringent in cases of diarrhoea, &c. Lead salts. (1) Normal lead acetate or sugar of lead, (CH 3 .COO) 2 Pb + 3H 2 0, is manufactured from sheet-lead and acetic acid. It forms colourless lustrous four-sided prisms, which are poisonous and of a ^ nauseous sweet taste. It combines with lead oxide to (2) basic salts of alkaline reaction, termed sub-acetates. 152 VI. MONOBASIC FATTY ACIDS The simplest basic salt has the composition OHPb0 CO-CH 3 , but there also exist others, e.g. OH-Pb-O-Pb-p- CO-CHg, &c. Two molecules of acetic acid can combine with as many as 5 molecules of lead oxide. These basic acetates are used as Goulard's lotion, and on the large scale for the preparation of white-lead, &c. Cupric acetate, Cu(C 2 H 3 2 ) 2 + 2H 2 0, dark-green crystals, also forms basic salts (verdigris). Silver acetate, AgC 2 H 3 2 , forms characteristic glistening needles. Detection of Acetic Acid. (1) When an acetate is heated with alcohol and sulphuric acid, the pleasant-smelling ethyl acetate is formed; (2) by means of the silver salt; (3) by the odour of cacodyl produced upon heating the potassium or sodium salt with arsenious oxide. (See p. 116.) Propionic acid, CH 3 .CH 2 -C0 2 H (Gottlieb, 1844), may be obtained by the reduction of acrylic or lactic acid (see pp. 143 and 144); also from lactate or malate of calcium by suit- able Schizomycetes fermentation (Fitz). It is usually prepared by the hydrolysis of ethyl cyanide (propionitrile) with alkalis. (See pp. 101 and 142.) Calcium chloride separates it from its aqueous solution in the form of an oil, whence its name TT/OWTOS, the first, and TTIWV, fat; the first oily acid. Butyric acids, C 4 H 2 . 1. Normal butyric acid, butane add, ethylacetic acid, CH 8 CH 2 CH 2 C0 2 H, occurs free in perspiration, in the juice of flesh, in the contents of the large intestine, and in the solid excrementa; as hexyl ester in the oil of the fruit of Heracleum giganteum, as octyl ester in Pastinaca sativa, and to the extent of 2 per cent as glyceride in butter (Chevreul, 1822). Formation. (See also General Modes of Formation.) It is produced (1) by the decay of moist fibrin and of cheese (being therefore contained in Limburg cheese); (2) by a Schizo- mycetes fermentation of glycerol, and of carbohydrates (Pelouzc and Gelisj Fitz; see below); (3) by the oxidation of albu- minoids with chromic acid, of fats with nitric acid, of coniine, &c., and (4) by the dry distillation of wood. Preparation. In the "butyric fermentation" of sugar or starch by fission ferments (e.g. Bacillus butyUcus), CaC0 3 or ZnO being added at the same time, to neutralize the acid formed. If the fermentation is brought about by impure material BUTYRIC AND VALERIC ACIDS 153 (decaying cheese, &c.), lactic acid is first produced by other micro-organisms, this being then converted into butyric acid by the butyric bacillus. Properties. It is a thick liquid of unpleasant rancid odour, in presence of ammonia like that of perspiration, is miscible with water, and separates from its aqueous solution on the addition of salts. B.-pt. 163. The calcium salt, Ca(C 4 H 7 2 ) 2 -f- H 2 0, forms glistening plates, and is characterized by being more soluble in cold than in hot water; it therefore separates on warming the concentrated cold aqueous solution. On pro- longed heating of the solution, however, it is transformed into the calcium salt of isobutyric acid. 2. Isobutyric acid, 2 - methyl - propane acid, dimethyl - acetic acid, (CH 3 ) 2 : CH C0 2 H, is present in the free state in the carob (Redtenbacher), in the root of Arnica montana, and as esters in Pastinaca saliva and Roman chamomile oil. It is obtained from isopropyl cyanide (Erlenmeyer), by the oxidation of isobutyl alcohol, by the aceto-acetic ester syn- thesis (p. 229), &c. It resembles w-butyric acid, but is more sparingly soluble in water (1 in 5), and boils 9 lower, i.e. at 154. Unlike the latter, however, it is easily oxidized to acetone or acetic acid, and carbonic acid. The calcium salt, Ca(C 4 H 7 2 ) 2 , differs from its isomer in being more^oluble in hot water than in cold. The solution is accompanied by a slight absorption of heat, whereas the solution of the salt of the 7i-acid is accompanied by a slight evolution of heat. Valeric acid, C 5 H 10 2 , exists in the four different modifica- tions which are theoretically possible: 1. Normal Valeric acid (Pentane acid), propyl-acetic acid, CH 3 .(CH 2 ) 3 .C0 2 H, from normal butyl cyanide (Helen and Rossi, 1871), is best prepared from propyl-malonic acid. (See B. 21, Ref. 649; also malonic ester synthesis.) It boils at 185, and is soluble in 27 parts of water. 2. Isovalerio acid, 3 -methyl -butane acid, isopropyl - acetic acid, (CH 3 ) 2 : CH I CH 2 C0 2 H, is obtained from isobutyl cyanide. It is found in the free state and in the form of esters in the animal kingdom and in many plants, especially (free) in the valerian root (Valeriana officinalis), and in the angelica root (Angelica archangelica), from which it is obtained by boiling with soda; further, in the blubber of the dolphin (Chevreul, 1817), in the berries of Viburnum opulus, in the perspiration from the foot, &c. The natural acid is usually mixed with the active valeric acid, and is therefore optically 154 VI. MONOBASIC FATTY ACIDS active; the oxidation of fermentation amyl alcohol by chromic acids yields a similar mixture. When pure it is optically in- active, boils at 175, and has an unpleasant pungent acid odour, like that of old cheese, and a corrosive action. It is used in medicine. 3. Methyl -ethyl -acetic acid, active valeric add, 2- methyl- /~1 TT butane acid, Q jj 3 ^>CHC0 2 H, occurs in nature, as already mentioned, and results from the oxidation of the active ( ) amyl alcohol; it is in this case (+) optically active, while, if prepared synthetically, e.g. by the aceto-acetic ester re- action, it is optically inactive, but can be resolved by suitable methods into a -j- valeric acid and a valeric acid. [For determination of optical activity, see section on Physical Properties.] There are thus three distinct acids, one dextro-rotatory, one Isevo - rotatory, and the third optically inactive, which have to be represented by the same structural formula, viz.. As regards their ordinary chemical and physical properties, the two active acids are exactly alike, and differ only in their action on* polarized light. This difference is not due to the different arrangements of the molecules, as all three are liquids, and in liquids the molecules are not usually regarded as having definite arrangements. A further proof that the cause of the activity, and hence of the isomerism, is to be sought for in the molecules themselves, and not in any special arrange- ments of the molecules, is the fact that the optical properties of the acids in the gaseous state are similar to those in the liquid. The investigations of Pasteur, Le Bel, and VaiHt Hoff have shown that this kind of isomerism, which is now usually termed stereo-isomerism, is due to the fact that the com- pound contains a carbon atom to which 4 different radicals are attached; in the case of valeric acid these are, H, CH 3 , C 2 H 5 , C0 2 H. Such a carbon atom is usually termed an asym- metric carbon atom. (This expression does not mean that the carbon atom itself is asymmetric in shape, but that it is attached to four distinct radicals, and as we shall see later this pro- duces an asymmetric molecule.) Varit Hoff showed that if we assume that these radicals are arranged around the carbon atom, not in a single plane, but in the three dimensions of space, then every compound con- STEREO-ISOMER1SM 155 taining a single asymmetric earbon atom should exist in the modifications represented by the figures 1 and 2. b I I. 2. Such modifications are not identical, since they cannot be brought to superposition (this can be shown readily by the aid of models), but they are very similar; in fact, they stand in the relationship of the right to the left hand, or, in other words, in the relationship of an asymmetric object to its mirror image. The spatial relationship of the radicals is often expressed by stating that if the asymmetric carbon atom is situated as the centre of a regular tetrahedron, then the four radicals occupy the solid angles of the tetrahedron. The arguments in favour of the spatial representation of the molecules of carbon compounds are largely based on a consideration of the number of isomeric forms in which simple carbon deriva- tives occur. For example, no simple compound of the type Caabb is known to exist in more than one modification. If, however, the radicals and carbon atom were arranged in a single plane, we should expect the two modifications: b but with the spatial or tetrahedral arrangement we can get but the one modification. a 156 VI. MONOBASIC FATTY ACIDS An examination of models* will clearly show that in what- ever way we exchange the radicals a and b, we always arrive at a figure which can be superimposed on the one depicted. Similarly with regard to compounds C a a b c, in which 2 of the 4 radicals are alike. The tetrahedral arrangement allows of one modification only, and in these cases only one is actually known. When, however, all four radicals are distinct, e.g. Cabcd, the spatial arrangement, as we have already seen, admits of two configurations, which are in the relationship of object to mirror image, and these two modifica- tions undoubtedly represent the two optically active isomerides, in which almost every compound of the type Cabcd has been shown to exist. An examination of the models repre- senting the two modifications shows that they are both asym- metric, i.e. a plane of symmetry cannot be drawn through them, and the optical activity which such compounds exhibit when in the liquid state, or in solution, is undoubtedly con- nected with the asymmetry of their molecules. Since the two configurations contain the same radicals and are very similar, in the one case containing the 4 radicals arranged in what we may term a positive, and in the other, in the opposite or negative direction, we should expect the molecules of the two compounds to produce rotations of the polarized ray equal in magnitude but of opposite sign. This is the case with the two optically active valeric acids: the pure dextro- acid has a rotation of + 17 '85, and the laevo-acid 17-85. In addition to the two optically active modifications, a third isomeride is usually known which is optically inactive. As it can be synthesised by mixing together equal weights of the d and I compounds, it follows that such a compound is either a mixture or a definite compound of the two active isomerides, i.e. its optical inactivity is owing to the fact that the two components are present in equal quantities. Such isomerides are often spoken of as racemic compounds, and are optically inactive by external compensation. Such racemic compounds may be resolved into their optically active components by * In using models it must be remembered that the models are not sup- posed to represent in the least the actual shapes of the atoms, but merely their spatial relationships. It must also be borne in mind that the atoms and radicals in the molecules are in a state of motion, and the fixed posi- tion represented in the model may be supposed to represent the mean position of the centre of gravity of any particular atom in its oscillatory motion, or the position which the centre of gravity would occupy at absolute zero. HIGHER FATTY ACIDS 157 several methods, most of which were devised by Pasteur. (See Kacemic Acid.) Relationship between Asymmetry of the Molecule and Optical Activity. Since the two isomerides of the type Cabcd are optically active, it should follow that any derivative of valeric acid in which the four radicals attached to the central carbon atom are still different should be also optically active, but that a derivative in which two of the radicals become similar should become inactive. This question has been examined by Le Bel in the case of some forty derivatives of active amyl C H H alcohol, Q H^^^CH OH' ^ e a l c hl i ts chloride, amine, all its esters, its oxidation product, viz. valeric acid, and all its salts, esters, &c., are optically active: the hydrocarbon C H H Q jj^C^CH ^ ta ^ ne( ^ ky reducing the chloride is, however, op- tically inactive, and cannot be resolved into active components. 4. Trimethyl-acetie acid, pivalic acid, (CH 3 ) 3 CC0 2 H, can be prepared from tertiary butyl cyanide (Butleroff, 1873). It melts at 35, boils at 164, and has an odour like that of acetic acid. Of the hexylic acids, eight are theoretically possible, and of these seven are already known. The most important among them is normal caproic acid, CH 3 (CH 2 ) 4 - C0 2 H (Cheweul, 1 822), which is found in nature, e.g. in cocoa-nut oil, Limburg cheese, and as a glyceride in the butter made from goats' milk, and is produced in the butyric fermentation of sugar, and by the oxidation of albuminous compounds and of the higher fatty acids, &c. Like valeric acid, it has a very unpleasant and per- sistent odour of perspiration and rancid butter. B.-pt. 205. The higher acids which are found in nature are all of normal constitution, and contain for the most part an even number of carbon atoms. Goats' butter contains the acids C 6 , C 8 , and C 10 , hence the names caproic, caprilic, and capric acids, and cocoa-nut oil in addition to those three the acid C 12 . This last, lauric acid, is contained more especially in oil" of laurels (Laurus nobilis) ; myristic acid, 0^ is present in oil of iris and nutmeg butter (from Myristica moschata); arachidic acid, C 20 , in the oil of the earth-nut (Arachis hypo- gcea); behenic acid, C 22 , in oil of ben (Moringa oleifera); cerotic acid, C 26 , forms in the free state the chief constituent of bees'-wax, and as ceryl ester that of Chinese wax. Pal- mitic acid, C 16 H 32 2 , and stearic acid, C 18 H 36 O 2 (pp. 158 and 161), are very widely distributed, being nearly always accom- 158 VI. MONOBASIC FATTY ACIDS panied by a third acid poorer in hydrogen, viz. oleic acid, CjoH^Og (see Unsaturated Acids). Most animal and vegetable fats and oils, e.g. tallow, suet, butter, palm, olive and seal oils, consist almost entirely of a mixture of the glyceryl esters of palmitic, stearic, and oleic acids, these esters being termed, for the sake of brevity, palinitin, C 3 H 5 (O.CO.C 15 H 31 ) 3 , stearin, C 3 H 5 (0 CO C ir H 35 ) 3 , olein, C 3 H 5 (0 CO C ir H 33 ) 3 . Palmitin and stearin being solid and olein liquid, the consistence of a fat or oil depends on the preponderance or otherwise of the solid esters. The consti- tution of the fats was elucidated by Chevreul in 1811. Eancidity consists, in the case of many fats, of a partial sa- ponification, whereby strongly smelling fatty acids are set free. Most of the varieties of wax are, on the contrary, esters of monohydric alcohols; thus bees'-wax consists of the melissic ester of palmitic acid, C 30 H 61 CO C 15 H 31 , together with free cerotic acid, Chinese wax (from Croton sebiferum, the tallow- tree) of the ester C^H^O CO C 26 H 53 , and spermaceti (Ceta- ceum, in the skull of Physiter macrocephalus) of the ester C 16 H 33 O.CO.C 15 H 31 . From all these esters the acids are obtained in the form of potassium salts by saponification with alcoholic potash, thus : C 3 H 6 (O.CO.C 17 H 36 ) 3 + 3KOH = 3C ir H a5 C0 2 K + C 3 H 6 (OH) 3 Stearin Potassic stearate Glycerol. The separation of the acids is effected by fractional crystal- lization, fractional precipitation with magnesium acetate, or by fractional distillation either of the fats themselves or of their esters in a vacuum. Oleic acid can be separated from palmitic and stearic by taking advantage of the solubility of its lead salt in ether. The stearine candles of commerce consist of a mixture of palmitic with excess of stearic acid, some paraffin or wax being usually added to prevent them becoming crystalline. The manufacture of candles depends upon the saponification of the solid fats, especially of beef and mutton tallow, by means of water and lime, of concentrated sulphuric acid, or of super- heated steam. Soaps consist of the alkaline salts of palmitic, stearic, and oleic acids, hard soaps containing sodic salts, chiefly of the solid acids, while soft soaps contain potassic salts, principally oleate. By the addition of common salt to a solution of a potassic soap, the latter is converted into a sodic soap, which is insoluble in SOAPS 159 a solution of sodic chloride. This process is usually termed "salting out", and is analogous to the precipitation of sodic chloride by the addition of hydric chloride to its saturated solution. (Cf. Walker, "Phys. Chem.", p. 314.) These alkali soaps dissolve to a clear solution in a little water, but with excess of water are hydrolysed to a certain extent, yielding free alkali and free fatty acid or acid salt, analogous to potassic peracetate. The cleansing action of soap is usually attributed to the presence of the small amount of free alkali thus formed : + NaOH. This hydrolysis is similar to that observed in the case of inorganic salts derived from a feeble acid and a strong base, and increases with increasing dilution. The production of free alkali (or free hydroxyl ions) can be readily understood by aid of the theory of ionization. The salt RC0 2 Na, when dissolved in water, may be assumed to be ionized to a certain extent in the normal manner, thus giving rise to cations Na and anions RC0 2 . But water itself is ionized to a slight + + extent to H and OH ions, and we should thus have H and RC0 2 ions in the same solution; the acid from which the sodic salt is derived is a feeble acid, and hence shows little tendency to ionize, and thus the H and R'C0 2 ions will unite to form non-ionized molecules RC0 2 H. This implies removal of hydrions from the sphere of chemical action, and a certain number of water molecules will be ionized in order to supply fresh hydrions ; these will again unite with the acid ions, and the two reactions will proceed until a state of equilibrium is established. In this state of equilibrium we shall have R.C0 2 , Na, H, OH ions and R-C0 2 H and H 2 molecules; but it is obvious that the OH ions will be largely in excess of the H ions, since a considerable number of these latter have been used up in forming non-ionized molecules of acid. The solution, as a whole, will thus possess more or less pronounced alkaline properties. (Cf. Walker, "Phys. Chem.", p. 290.) The calcium, barium, and magnesium salts are insoluble in water, but partly crystallizable from alcohol. The preci- pitates produced by the action of hard waters on soaps consist 160 VI. MONOBASIC FATTY ACIDS largely of those insoluble salts. The lead salts are prepared by boiling fats with lead oxide and water, and form the so- called plaisters or lead plaisters. The higher acids with an uneven number of carbon atoms, C n , C 13 , C 15 , and C 17 , are prepared synthetically from the acids containing 1 atom of carbon more, by transforming them into the ketones C^H^^CO'CHa (p. 131), and oxidizing these, when acids C n _ 2 H 2n _ 3 COOH are obtained. (Krafft.) On these reactions a method for proving that the higher fatty acids, e.g. palmitic and stearic, are normal in constitution has been based. (See Caution, p. 132.) The acid C 15 H 31 C0 2 H is converted into the ketone C 15 H 31 COCH 3 ; this on oxidation yields C 14 H 29 C0 2 H and acetic acid. The conversion into ketone and subsequent oxidation is re- peated, and an acid, C 13 H 27 -C0 2 H, obtained. The processes are repeated until an acid, CH 3 (CH 2 ) 7 C0 2 H, ?i-nonylic acid, is obtained. This can be shown to have a normal structure by synthetical methods, and hence all the higher acids must also have a normal structure, since if the acid C 13 H 2lr 'C0 2 H had not a normal structure, but contained a side chain, e.g. Q jj 3 ^>CHC0 2 H, on conversion into the ketone and sub- sequent oxidation it would not yield the acid, C 12 H 25 -C0 2 H, but a ketone, CH 3 CO C n H 23 , or the oxidation products of this ketone. Dissociation constant. One of the most characteristic physical constants of the organic acids is what is termed the dissociation or affinity constant K, which is derived from the equation k = -, =, where v = volume of solution v (1 a) in litres containing 1 gram mol. of the acid, a is the amount ionized, and 1 a the amount not ionized. This equation is based on the law of mass action. In the case of any feeble organic acid, e.g. acetic acid, where we have 1 gram molecule dissolved in v litres of solution, a state of equilibrium repre- sented by the equation + CH 3 .COOH ^ CH 3 "COO + H occurs. Then if ^ and Jc 2 represent the velocity constants of the direct and reverse reactions, we have, according to Guld- berg and Waage's law, at the stage of equilibrium: *, X !^ = k X ? X or ^ = | = * v v v v(l a} UNSATURATED ACIDS 161 The extent of ionization in a solution containing 1 grain molecule in v litres is determined by electrical conductivity determinations, a = , i.e. the degree of ionization at a dilution v is the ratio of the molecular conductivity at this dilution to the molecular conductivity at infinite dilution when all the acid molecules are ionized. (Cf. Walker, pp. 232-235.) For a weak acid, k remains constant, and affords a convenient measure of the strength of an organic acid. As a rule, the constant is usually taken as 100 times k, or K = 100 k. Acid. K. Formic. Acetic. Propionic. 7i-Butyric. iso-Butyric. 0-0214 0-00180 0-00134 0'0015 0'00144 Formic acid is obviously much the strongest of the fatty acids, but they are all comparatively weak acids compared with the strong mineral acids. Close comparison cannot be a? drawn between the two groups, as the equation k = n__ a \ v does not hold good for strong acids. Palmitic acid (hexadecane acid), CH 3 '(CH 2 ) 14 .C0 2 II, is most conveniently prepared from palm-oil, which is a mixture of palmitin and olein; also by fusing oleic acid or cetyl alcohol with potash. M.-pt. 60. Stearic acid, CH 3 .(CH ? ) 16 'C0 2 H, is formed, among other methods, by reducing oleic acid, and is also obtained from the so-called shea-butter or from mutton suet. M.-pt. 68. "Artificial ivory" consists of gypsum which has been saturated with liquid stearic acid. B. Unsaturated Acids, C u H 2n _A or CJL Melting-pt. Boiling-pt, Acrylic acid CoH^Oo 7 140 (la 72 182 Crotonic acids, C 4 H 6 O 2 Jib Li 15 16 172 160 Angelic acidl n TT n Tiglicacid ) G 5 H 82- 45 65 185 198 Olpir* arirt (7 hi ()> 14 Erucic acid CXofJ^O? . 33 ( B 480 ) 162 VI. MONOBASIC FATTY ACIDS These acids are known as the acids of the oleic series. In their physical properties they closely resemble the saturated acids, apart from differences in melting-point, which are some- times considerable. They have the chemical properties char- acteristic of monobasic acids; they yield salts, esters, amides, &c., in much the same manner as the saturated acids; but in addition they resemble the olefines in the readiness with which they yield additive compounds with hydrogen, halo- gens, or halogen hydrides, thus forming fatty acids or their substitution derivatives. Thus oleic acid, C 18 H 34 2 , when treated with H 2 in presence of colloidal Pd, yields steanc acid, C 18 H 36 2 , and with bromine, dibromo - stearic acid, C 18 H 34 Br 2 2 . In this way they characterize themselves as derivatives of the unsaturated hydrocarbons of the ethylene series, from which we may imagine them to be formed by the replacement of an atom of hydrogen by carboxyl. They may therefore be termed olefine-carboxylic acids. Upon the addition of halogen hydride, the halogen does not always attach itself to that carbon atom to which the smaller number of hydrogen atoms is united. The presence of the double bonds renders them much more sensitive to oxidizing agents than are the fatty acids. When a very dilute oxidizing agent is employed, e.g. 1 per cent permanganate, dihydroxy derivatives of fatty acids are ob- tained : CH 3 .CH:CH.C0 2 H + + H 2 = CH 3 .CH(OH).CH(OH).CO 2 H; but if stronger oxidizing agents are employed, a rupture of the molecule occurs at the position where the double bond exists, and a mixture of acids is obtained: CH 3 CH : CH CH 2 . CO 2 H CH 3 CO 2 H and C0 2 H CH 2 CO 2 H. This affords an excellent method for determining the position of the double bond in the molecule of the acid. Fusion with caustic alkalis also causes a breaking up of the molecules, and the formation of a mixture of fatty acids; but this reaction is of no use for determining the position of the double bond, as treatment with alkali tends to shift the double bond, if possible, nearer to the carboxylic group. Fittig (B. 1891, 24, 82, &c.) has studied the action of dilute alkalis on a number of un- saturated acids, and always observed the same effect, e.g. bydrosorbic aci4, CH 3 CH 2 CH : CH CH 2 COOH, passes into FORMATION OF UNSATURATED ACIDS 163 OH 3 CH 2 . CH 2 CH : CH . COOH (2 - hexene - 1 - add). Such changes, which are termed " molecular transformations ", are sxplained by the assumption that atoms or radicals (in this sase the elements of water) are added on to the original compound, and then eliminated in a different manner, e.g. : CH 3 .CH:CH.CH 2 .CO 2 H GHo.CH 2 .CH(OH).CH 2 .C0 9 H -> CH 3 .CH 2 .CH:CH.C0 2 H. The presence of the double bond in the molecule has a con- siderable effect upon certain properties of the acid; for ex- ample, the dissociation constant and the rate of esterification )y the catalytic method. Fichter and Pfister have shown (Abs. 1904, i. 965) that the ntroduction of a double bond usually increases the strength of an acid, and that the effect is most marked when the double xmd is in the /2-y-position, e.g. butyric acid, K = '00 154; cro- ;onic acid, K = 0-00204; and for vinyl acetic, K = 0-00383. Sudborough (J. C. S. 1905, 1840; 1907, 1033; 1909, 315, 975) has shown that the introduction of the double bond in the a-position greatly retards esterification. The rates for hydrocinnamic, C 6 H 5 GEL CH 2 C0 2 H, and for cinnamic acid, 6 H 6 .CH:CH.C0 2 H, are as 40:1. Modes of Formation. 1. By oxidizing the corresponding Icohols or aldehydes, e.g. acrylic acid from allyl alcohol or acrolein. CH 2 :CH-CH 2 .OH CH 2 :CH-CHO -> CH 2 :CH.C0 2 H. 2. From the unsaturated alcohols or their iodides, by con- verting them into nitriles and hydrolysing these, e.g. crotonic acid from allyl iodide (intramolecular rearrangement, p. 164). CH 2 :CH.CH 2 I CH 3 .CH:CH.CN CH 3 -CH:CH.CO 2 H. Both these methods of formation are analogous to those of .he fatty acids. 3. From the monohalogen substitution products of the satu- rated fatty acids, by warming with alcoholic potash, sometimes upon simply heating with water. This reaction is analo- gous to the formation of the olefines from alkyl haloids ; it occurs in the case of those substituted acids which contain the halogen in the ^-position to the carboxyl (see p. 167 164 VI. MONOBASIC FATTY ACIDS 4. From the halogen substitution products of the unsati rated acids by inverse substitution: CH 3 .CH:CC1.CO 2 H CH 3 .CH:CH.C0 2 H. 5. By the elimination of water from hydroxy fatty acids. CH 2 (OH).CH 2 .COOH = CH 2 :CH.(X) 2 H + H 2 O Ethylene-lactic acid Acrylic acid. This reaction corresponds with the formation of the olefine from monohydric alcohols. Constitution and homers. The constitution of the unsaturate< acids, C n H 2n _2O2, follows from their behaviour as monobasi acids and as unsaturated compounds, and the position of th double bond is ascertained by the process of oxidation. Th number of isomeric acids, C m K< im _i C0 2 H, is the same as th number of isomeric unsaturated alcohols, C^H^^-OH. Acrylic acid, propene acid, ethylene-carboxylic acid, CH 2 :CH C0 2 H (Redtenbacher), is prepared by the oxidation of acrolei by oxide of silver, or by the distillation of /3-iodopropioni acid with oxide of lead. (Cf. mode of formation 3.) It i very similar to propionic acid. Mixes with water and readil polymerizes. It is reduced to propionic acid when warmei with zinc and sulphuric acid, and is decomposed when fuse< with alkali into acetic and formic acids. Acids, C 4 H 6 2 . Four isomeric acids with this formula ar known. 1. Ordinary or solid crotonic acid (2-Buten-l-acid] CH 3 CH : CH C0 2 H, occurs along with isocrotonic aci< in crude pyroligneous acid, and is prepared from allyl iodid by means of the cyanide, which, instead of having the antici pated formula, CH 2 : CH CH 2 CN, has the isomeric one CH 3 'CH:CHCN; this affords another example of molecula transformation. It is also prepared by heating malonic acid with para aldehyde and glacial acetic acid: It crystallizes in large prisms, melts at 72, boils at 189, ha an odour like that of butyric acid, and is fairly soluble ii water. On reduction it yields ?i-butyric acid, and on carefu oxidation, oxalic acid, hence the constitution. 2. Isocrotonic acid, CH 3 -CH:CH.C0 2 H, obtained by tin OLEIG AClt> 165 tction of sodium amalgam upon chloro-isocrotonic acid, melts it 15, boils .at 172, and changes into ordinary crotonic acid it 180. It is present in croton-oiL For preparation of the mre acid see Morrell and Cellars, J. C. S. 1904, 345. Isocrotonic acid was formerly regarded as CH 2 :CHCH 2 }0 2 H, but it shows almost the same chemical behaviour as 3rotonic acid, e.g. on reduction and oxidation, or on addition )f hydrogen bromide, and is now regarded as having the same .tructural formula as, but being stereo-isomeric with, solid TO tonic acid. (Cf. Fumaric and Maleic acids.) 3. Meth-acrylic acid, 2-methyl-2-propene-l-actd, CH 2 : C<^QQ Vr, s found in small quantity in Eoman chamomile oil, and may be obtained by the withdrawal of HBr from bromo-isobutyr.c icid: t smells like decaying mushrooms, and melts at 15. 4. Vinyl-acetic acid, CH 2 : CH . CH 2 C0 2 H, 1-ButeneA-acid., nay be obtained synthetically. Angelic acid, CH 3 CH : C(CH 3 )C0 2 H, is present in the an- gelica root, and, together with its stereo-isomer, tiglic acid, in .ioman chamomile oil. (Cf. A. 250; 259, 24; 272, 1; 273, 127.) PIC relationship of these two acids is exactly the same as that of crotonic and isocrotonic acids. Oleic acid, C 18 H 34 2 (Chevreul), is present as olein (glyceryl oleate) in the fatty oils especially, e.g. olive, almond, and train oils. It is a colourless oil, solidifies to white needles in the cold, melts at 14, and cannot be volatilized without decom- position. It is tasteless and odourless, and has no action upon litmus, but quickly becomes yellow and acid by oxi- dation in the air, and also acquires a rancid odour. Its lead salt is soluble in ether, and by this means the acid ^ may be separated from numerous other organic acids. It yields, on fusion with potash, the saturated acids, palmitic and acetic. Nitrous acid converts it into the stereo-isomeric crystalline elai'dic acid, melting at 45. It contains a normal chain, since on reduction it yields stearic acid. When carefully oxidized, it yields pelargonic acid, CH 3 (CH 2 ) 7 C0 2 H, and azelaic acid, C0 2 H.(CH 2 ) 7 -C0 2 H, and hence the constitu- tional formula: CH 3 .(CH 2 ) 7 -CH:CH.(CHo) 7 .C0 2 H. 166 VI. MONOBASIC FATTY ACIDS Erucic acid, C 22 H4 2 2 , occurs in rape-seed oil, melts at 33' and on treatment" with nitrous acid yields the stereo-isomeri brassidic acid, melting at 60. The constitution is probably : CH 3 [CH 2 ] 7 CH : CH[CH 2 ] n CO 2 H. iFor the stereo-chemistry of the unsaturated acids, see Fumari <and Maleic acids. C. Propiolic Acid Series, C n H 2u _/> 2 The acids of this series again contain two atoms of hydroge; less than those of the former, and are to be regarded as cai boxylic acids of the acetylene hydrocarbons, e.g. propiolic acid CH:CC0 2 H, as acetylene-carboxylic acid. They can ac cordingly be prepared by the addition of C0 2 to the sodiur derivatives of the acetylenes (analogously to mode of formatioi 4 of the saturated acids, p. 143). They closely resemble the unsaturated acids which have beei already described, but differ from them by the fact that eac" molecule of such an acid can combine with either 2 or 4 atom of hydrogen, chlorine, bromine, &c., and can yield explosiv compounds with ammoniacal silver and copper solutions There are, however, acids of the formula C n H 2n _ 4 2 which d not possess this last peculiarity, viz., those which are derived not from the homologues of acetylene proper, but from thei isomers, and which therefore contain two double bonds instea* of a triple one. (Compare Acetylene Hydrocarbons, p. 51.) The most important member of the series is propiolic o propargylic acid, pi-opine add, CH:C-C0 2 H, which corn sponds with propargyl alcohol, and is prepared by warmin an aqueous solution of the acid potassium salt of acetylene-d carboxylic acid, the latter being itself obtained from dibronu succinic acid. (See p. 241, also B. 18, 677.) In its physic* properties it resembles propionic acid, forms silky crystal below 6, and boils at 144. It is readily soluble in wate and alcohol, and becomes brown in the air. It gives, even i dilute solution, the characteristic explosive silver precipitate, Tetrolic acid, CH 3 'C:C-C0 2 H, is obtained from /3-chlor< crotonic acid and aqueous potash, and melts at 76. Sorbic acid, CH 3 .CH:CH.CH:CH.C0 2 H, is contained i the juice of the unripe sorb apple (Sorbus Aucuparia), and ha relatively high melting- and boiling-points. I o < o 53 c3 ,Q O s a - o W "cc 1 g I g J> fl ^ O !^ 2 S3 0} 5 "" O5 CQ ^^ r ^ = ' w ^ S) J -2 73 o W g 1 O rt< 00 CO i i O 00 O O i i O 10 # CO . .t-r^O <? T" f <? - 1 : :<?wp o o o .-H o o o o (M O5 . . . O . : : : p : eo O CO CO G> O) G<J CT G^ ' OOOOO ,_, o o o o CM CO w w ^^S6 ,' <N' C* wPQ MpcjMH oooo ^ cdfldooPgP OP4so:j.tt^Qi.a aoa. 167 168 VI. MONOBASIC FATTY ACIDS The acids poorer in hydrogen also yield similar substitution products, e.g. CH 2 : CC1 C0 2 H, a-chlor-acrylic acid; CHBr: CH.C0 2 H, -brom-acrylic acid; CH 3 - CH : CC1 C0 2 H, a-chlor- crotonic acid; CI:CC0 2 H, iodo-propiolic acid, &c. All these halogen derivatires have the properties of mono- basic acids; in many respects they resemble the parent sub-- stances, but as a rule are much stronger acids. This is ex-* tremely well shown in a comparison of the dissociation con- stants K. (See table.) Since their acid nature remains unaltered, they still contain the carboxyl group; the halogen has therefore replaced the hydrogen of the hydrocarbon radical. They may also be looked upon as haloid substitution products of the hydro- carbons, in which 1 atom of hydrogen is replaced by carboxyl : CH 3 C1 (chloro-methane) CH 2 C1 C0 2 H (chlor-acetic acid). The modes of formation and properties of these substituted acids also coincide with this view. Tkus, while they show a behaviour perfectly analogous to that of the non-substituted acids, forming salts, esters, chlorides, anhydrides, and amides, their halogen atoms are as readily exchangeable for OH, CN, or S0 3 H, as are those of the substitution products of the hydrocarbons. (See p. 61.) homers and Constitution. While in each case only one mono-, di-, &c., halide acetic acid exists, two isomeric monohaloid propioni'c acids are known. This is readily explicable from the fact that in propionic acid, CH 3 CH 2 C0 2 H, the two a-hy- /3 a drogen atoms are differently situated from the three /?- ones, the former being attached to the carbon atom nearer to the carboxyl, and the latter to that one farther from it. According to theory, therefore, with which the observed facts agree, the following two isomers are possible : CH 3 .CHX.C0 2 H and CH 2 X.CH 2 -C0 2 H a-Haloid-propionic acid jS-Haloid-propionic acid. These acids yield two isomeric lactic acids by exchange of their halogen for hydroxyl, thus : GH 3 .CH(OH).C0 2 H and CH 2 (OH).CH 2 .CO 2 H Common lactic acid Ethylene-lactic acid. The constitution of both of these lactic acids follows from their other modes of formation (see p. 207, et seq.). The FORMATION OF HALOID FATTY ACIDS 169 positions of the halogens in the a- and ft- substituted propionic acids are thus also fixed. Those substituted acids which contain the halogen attached to the a-carbon atom, i.e. to the same carbon atom to which the carboxyl group is united, are termed a-acids, and the others /?, y, &c., acids, the successive carbon atoms in their order from the carboxyl group being designated as a, /?, y, &c. We thus distinguish, for instance, between a-, /3-, and y- chloro-butyric acids, aa-, aft-, and fifi- dibromo-propionic acids, &c. Two stereo-isomeric forms of the a- or /?- mono-chloro- and -bromo-crotonic acids are known (A. 248, 281), being derived from crotonic and isocrotonic acids respectively. Formation. (a) Of the saturated substituted acids. 1. Chlorine and bromine can substitute directly, the halogen taking up the a-position to the carboxyl. The reaction is often carried out in sunlight and in the presence of a halogen carrier. One of the commonest methods is to transform the acid into the acid bromide by the aid of phosphorus and bromine, and then to brominate. The pro- duct obtained, e.g. CH 3 CHBr COBr, on treatment with water yields the a-bromo acid, CH 3 CHBr.C0 2 H. This is generally known as the Hell-VoUmrd-Zelinsky method. Trimethyl acetic acid, CMe 3 C0 9 H, which contains no a-hydrogen atom, cannot be brominated in this manner (B. 1890, 23, 1594). 2. From hydroxy acids of the gly collie series by the action of PC1 5 , HBr, &c., e.g. : CH 3 .CH 2 .CH(OH).CO 2 H -> CH 3 .CH 2 .CHC1.C0 2 H. 3. By the addition of halogen or halogen hydride to the unsaturated acids. (b) Of the unsaturated substituted acids. These are often prepared by the elimination of HC1, HBr, or HI from poly- halogen derivatives of the fatty acids: CH 3 - CHBr- CHBr- CO 2 H -> CHs-C or by the addition of hydrogen halide to propiolic acids. Behaviour. 1. For the replacement of chlorine, bromine, and iodine by hydroxyl, see p. 206. This exchange takes place with more difficulty in the a-monochloro-substituted acids than in the corresponding bromine and iodine com- pounds, but more easily than in the case of the alkyl chlorides, and it is effected by means of moist silver oxide, 170 VI. MONOBASIC FATTY ACIDS or frequently by prolonged boiling with water alone (A. 200, 75). In this way monochlor-acetic yields glycollic acid: CH 2 C1.C0 2 H + H 2 O = OH.<JE 2 .CO 2 H /2-halogen acids, on the other hand, lose halogen hydride when boiled with water, and yield unsaturated acids, together with C0 2 and olefines C n _ 1 H 2n _ 2 . y-halogen acids break up under these conditions (even with cold soda solution) into HC1, &c., and a lactone, i.e. an anhydride of a y-hydroxy-acid (see p. 217; cf. Fittig, A. 208, 116). 2. When boiled with an alcoholic solution of potassium cyanide, cyano-fatty acids are produced: CH 2 C1.C0 2 K These compounds are on the one hand monobasic acids, and on the other nitriles, and they consequently yield dibasic acids when hydrolysed. In the above case malonic acid, C0 2 H.CH 2 .C0 2 H, is formed. 3. They form sulphonic acids with sodium sulphite, e.g. : CH 2 a.C0 2 Na + Na.S0 3 Na = NaSOj-GHj-OOjNa + NaCl. These latter are compounds which, apart from the acid character they derive from the carboxyl group, are actual sul- phonic acids, like ethyl-sulphonic acid, and are thus dibasic. Their sulpho-group can, however, be replaced by OH on boiling with alkalis. 4. With AgN0 2 , under favourable conditions, nitro-deriva- tives of the fatty acids are formed, and these yield amino- acids on reduction, e.g. NH 2 - CH 2 C0 2 H. (B. 1910,43,3239.) Chloroformic acid, Cl C0 2 H, has so far not been prepared, although derivatives of it are known. (Cf. Chloro-carbonic acid.) The chlorinated acetic acids are formed by the direct sub- stitution of acetic acid, or better, of acetyl chloride, chlori- nated acetyl chlorides ensuing in the latter case as inter- mediate products. Monochlor-acetic acid (Chloro-ethane acid), CH 2 C1C0 2 H, is prepared by chlorinating acetic acid, preferably in the pre- sence of acetic anhydride, sulphur, or phosphorus. It forms rhombic prisms or tables and corrodes the epidermis. Di- chlor- acetic acid, CHC1 2 C0 2 H, is more conveniently ob- tained by warming chloral hydrate with potassium cyanide (B. 10, 2120), and trichlor- acetic acid, CC1 3 C0 2 H, by ACID DERIVATIVES 171 oxidizing chloral hydrate with nitric acid. The former de- composes with boiling alkali to oxalic and acetic acids, and the latter to chloroform and carbon dioxide. Inverse sub- stitution reconverts tri-, di-, and monochlor-acetic acids into acetic acid (Melsens, 1842). Sulpho-acetic acid, S0 3 HCH 2 C0 2 H, forms deliquescent prisms containing 1J mols. H 2 of crystallization. Its salts crystallize well. Cyano-acetic acid, CN.CH 2 .C0 2 H, is a crystalline substance melting at 65-66 and readily soluble in water; it decomposes into aceto-nitrile, CH 3 CN, and C0 2 when heated, and yields malonic acid on hydrolysis. a-Chloropropionic acid, CH 3 CHOI C0 2 H, is obtained by the action of PC1 5 upon lactic acid, and decomposition of the lactyl chloride, CH 3 CHC1 COC1, by water. /Modopro- pionic acid, CH 2 I CH 2 C0 2 H, is prepared by acting upon gly eerie acid, CH 2 (OH) . CH(OH) C0 2 H, with iodide of phos- phorus (exchange of 2 OH for 21 and of I for H); also by acting on acrylic acid with hydriodic acid. It forms colour- less six-sided tables of a peculiar odour; m.-pt. 82. The two cyanopropionic acids, C 2 H 4 (CN) C0 2 H, give the two succinic acids when hydrolysed. Chloro- and Bromo-crotonic acids, /3-Chloro-crotonic acid (2-Chlwo-2-JButene acid) (m.-pt. 94) and the stereo -isomeric /3-Isochloro-crotonic acid (m.-pt. 59-5) are formed by the action of PC1 5 on ethyl acetoacetate, and treatment of the product with water. The /3-chlor-iso-acid volatilizes with steam, but the /?-chloro-acid does not. VII. ACID DERIVATIVES A general idea of the kind of derivatives to which acids give rise is obtained by comparing these derivatives with cor- responding derivatives of the saturated monohydric alcohols, e.g. those of acetic acid with those derived from ethyl alcohol: CH 3 -CH 2 .OH Alcohol. CH 3 CH 2 ONa Sodium ethy late. CH 3 CH 2 Cl Ethyl chloride. CH S .CH 2 .SH Mercaptan. CH 3 .CH 2 'NH 2 Ethylamine. CH 3 CO OH Acetic acid. CH S CO ONa Sodium acetate. CH 3 *CH i X >0 Eth y 1 acetate - (CH 8 -CO) 2 Acetic anhydride. CH 8 CO Cl Acetyl chloride. CH 8 - CO SH Thiacetic acid. CHa-CO-NHz Acetamide. 172 VII. ACID DERIVATIVES It is seen that as regards formulae there is a close resem blance, the acetyl group taking the place of the ethyl group. Stated generally, the acid derivatives contain acyl radicals in place of the alkyl groups contained in the corresponding derivatives of alcohols. These derivatives are obtained by methods many of which are perfectly analogous to the modes of formation of the cor- responding alkyl derivatives, but they differ characteristically from these by being less stable towards hydrolysing agents. A number of other derivatives, viz. amido- and imido- chlorides, thiamides, imido-thio-compounds, and amidines, are peculiar to the acids: CH 8 CC1 2 - NHR*Amido-chlorides. CH 8 CC1 : NR Imido-chlorides. CH,.CS-NH 3 Thiamides. CH 8 .C(NH)OH Iimno-compounds. CH 8 .C(NH)SR Imino-thio- CH 8 .C(NH)(NH 2 ) Amidines. These compounds are also characterized by being readily hydrolysed. A. Esters of the Fatty Acids We have already seen that mineral acids readily give rise to esters by the replacement of their acidic hydrogen radicals by alkyl groups, e.g. S0 2 (OH) 2 S0 2 (OEt) 2 . In exactly the same manner the typical hydrogen of the fatty acids can be replaced by alkyl groups, and we get esters derived from the fatty acids, e.g. ethyl acetate, CH 3 C0 2 Et. Since these esters correspond with the metallic salts, they are sometimes termed alkyl salts. (Of. CHg . C0 2 K and CH 8 C0 2 Et. ) Methods of Formation. 1. By direct esterification, i.e. by direct action of the acid on the alcohol: = CH 3 .(X).ONa -fH-OH H = CH 3 .(X).OC 2 H 5 H- H-OH Although the equation representing the reaction is analogous to that representing the neutralization of acetic acid by an alkali, the process of esterification differs from that of neutrali- zation in two respects. (1) The reaction proceeds but slowly; thus, in the esteri- fication of acetic acid by ethyl alcohol the limit of the reaction at the boiling-point is not reached until after the lapse of * R signifies an alkyl radical either alphyl or aryl. ESTERIFICATION 173 several hours, and even then only two-thirds of the acid have been transformed into ester. (2) The reaction is a reversible or balanced one, and hence is never complete. The water which is formed during the process of esterification tends to hydrolyse the ester back into acid and alcohol : Thus, when equivalent quantities of acetic acid and ethyl alcohol are employed, only some 66 per cent of the acid becomes transformed into ester. It can readily be shown, by aid of Guldberg-PFaage's law of mass action, that by employing an excess of alcohol a larger proportion of acid will be con- verted into ester. Thus, in the above equation, if the original concentrations of the four substances expressed in gram mole- cules be denoted by a, b, o and o, and the velocity constants of the direct and reverse reactions by k^ and k 2 respectively, then after time t equilibrium will be established; and if we assume x gram molecules of acid have been esterified, then the concentrations of the four substances will be a x, b x, x and x. The rate of the direct reaction can be denoted by &! (a x ) (b x), and that of the reverse by & 2 x 2 (Guldberg and Waage). When equilibrium is established, the two reactions will proceed at the same rate, and k,(a-x}(b-x) = 2 * 2 , or (ax) (bx) _ constant f or a gi ven temperature. x- In the case of acetic acid and ethyl alcohol, using gram molecular proportions, i.e. a = b = 1, we find that equilibrium is established when some two-thirds of acid are esterified. Thus (! i)(l-"f) = constant, and the constant becomes equal to J. Then, supposing we alter the proportions of acid and alcohol, using 2 gram molecules of alcohol to 1 of acid, we have 4 = -85 (appro*.), 174 VIL ACID DERIVATIVES and thus 85 per cent of the acid will have been esterified in place of the 66 per cent when only 1 gram. mol. of alcohol was used. The reversible nature of the reaction is of especial importance in the preparation of ethyl acetate, and in this case the difficulty is overcome by the addition of a moderate amount of concentrated sulphuric acid, which is ordinarily supposed to react with the water, and thus prevent its hydro- lysing the ester. (Compare also Wade, J. C. S. 1905, 1656.) It is worthy of note that the limit of esterification does not vary to any large extent with the temperature. Thus, in the case mentioned above, the limit at 10 is 65 '2 per cent, and at 220 it is only 66*5 per cent. With most of the higher esters, and more especially the esters in the aromatic series, the limit of esterification is much higher, as the esters are not so readily hydrolysable. In these cases, however, the rates at which the esters are formed are extremely slow, and a catalytic agent is therefore introduced. The two common catalytic agents employed are: (1) A small amount of dry hydrogen chloride. At one time it was cus- tomary to saturate the boiling alcoholic solution of the acid with hydrogen chloride, but the researches of E. Fischer and Sprier (B. 1895, 28, 3201, 3252) have shown that the addition of 3 per cent of dry hydrogen chloride to the alcoholic solu- tion is quite sufficient. (2) A small amount of concentrated sulphuric acid, which acts in much the same manner as the hydrogen chloride. The use of these reagents is not to raise the limit of esterification, but to accelerate the production. In most cases, using the catalytic method at the boiling-point of the alcohol, the reaction is complete after three hours, and a 90-95 per cent yield of ester can be obtained by pouring into water. A number of researches have been made as to the influence of the constitution of the acid and of the alcohol on the rate of esterification, i.e. the amount of ester formed in unit time. Menschutkin, who employed the direct esterification method without a catalytic agent, i.e. the so-called auto -catalytic method, found that primary acids, i.e. RCH 2 -C0 2 H, were esterified most quickly; secondary acids, EE'CH-C0 2 H, were intermediate; and tertiary acids, RR'R"C'C0 2 H, least readily when the same alcohol was employed. Other researches tend to show that strong acids react with alcohol more readily than feeble acids in the absence of a catalyst. The velocity of esterification has also been determined for ESTERIFICATION 175 a number of acids employing the catalytic metnod (HC1). From the equation we should expect the reaction to be a bimolecular reaction, or a reaction of the second order; by altering the conditions, namely, by taking a large excess of alcohol as compared with the acid, the concentration of the alcohol may be regarded as constant, and the reaction then becomes unimolecular (H. Goldschmidt) and may be studied by the aid of the equation for unimolecular reactions, K = - log. - ; where K = the velocity constant, t time, a = concentration of the acid at the beginning of the ex- periment expressed in c.c. of standard alkali, and a x con- centration of the acid after the lapse of time t. Using this method, it is found that the introduction of any substituent (CH 3 , Cl, Br, I, C 6 H 5 , &c.) into the acetic acid molecule always lowers the velocity of esterification, the introduction of two such radicals, e.g. CHBr 2 C0 2 H, lowers the constant to a still greater extent, and when all three hydrogens are replaced by substituents, e.g. C(CH 3 ) 3 C0 2 H, the acid is esterified very slowly indeed as compared with acetic acid. These examples afford an extremely good instance of what is now generally termed steric retardation, or the retardation of a chemical reaction by the spatial relationships of radicals introduced into a molecule. The common theory of the process of esterification is that there is first direct union between a molecule of the acid and of the alcohol : + R'OH = X)H, yielding a dihydroxylic compound, which immediately elimi- nates water, yielding the ester R-C<^J . The introduction of radicals into the CH 3 group of the acetic acid molecule by filling up the space renders the formation of such additive compounds much more difficult, and hence the retardation of esterification (Wegscheider). The influence of the hydrogen chloride is purely catalytic; it remains unchanged at the end of the reaction. Its catalys- ing effect is undoubtedly due to to the hydrions it generates, as strong acids (HC1, HBr) are much better catalysing agents 176 VII. ACID DERIVATIVES than weaker acids (picric acid). (Cf. Goldschmidt, B. 1895, 28, 3218; Sudborough and others, J. C. S. 1898, 81; 1899, 467; 1904, 534; 1905, 1840.) 2. By the action of an acid chloride upon an alcohol or its sodium compound (cf. p. 179): 3. By the action of an alkyl haloid upon the salt of the acid: C 2 H 5 C1 + CH 3 CO.ONa = CH 3 .CO.OC 2 H 6 -f NaCl. As a rule, an alkyl iodide and the silver salt of the acid are employed. The ester can then be separated from the solid silver iodide and distilled. Occasionally the potassium salt and methyl sulphate are used. Reactions 2 and 3 are of very general application, and are largely made use of when an ester cannot readily be obtained by the catalytic method of esteri- fication. Properties. The esters are mostly neutral liquids which volatilize without decomposition; only those which contain a small number of carbon atoms in the molecule are soluble in water, e.g. ethyl acetate (1:14). 1. "Hydrolysis. They are all hydrolysed (saponified), i.e. resolved back into alcohol and acid, when heated, or better, superheated, with water, or when boiled with aqueous solutions of strong alkalis or mineral acids; with the simpler esters this hydrolysis is complete when the ester is allowed to remain for some time in contact with water or dilute alkali. The hydrolysis of an ester under the infli^nce of water or of mineral acids may be represented by the equation: K.CO 2 B'4-H.OH = K-CO-jH + K'-OH, and may be studied by the aid of the general equation for a uni-molecular reaction, K = - log. , since the concen- t a x tration of the water, if a large excess is used, may be regarded as constant. The action of the mineral acid is purely catalytic. The same result might ultimately be obtained by using water alone, but is considerably accelerated by using a small amount of a strong mineral acid (HC1, H 2 S0 4 ). Weak acids also ac- celerate the hydrolysis of the ester, but to a less extent. Ifc HYDROLYSIS OF ESTEKS 177 has been found, using the same ester and equivalent quantities of different acids, that the rate of hydrolysis is directly pro- portional to the strength of the acid. In other words, the catalysing influence of different acids is due to the hydrions. The hydrolysis of an ester by alkalis is represented by the equation: E . CO . OB' + NaOH = E-CO-ONa + R'-OH, and as it is analogous to the preparation of soaps by the action of alkalis on fats (p. 158), is commonly termed Saponification. This is a bimolecular reaction, and if equivalent quantities of ester and alkali are employed in solution, can be studied by aid of the equation K = - 7 -^- r, where t = time, a = initial t a(a x) concentration of alkali and of ester, a x = concentration of these after time t. The concentrations can readily be deter- mined by direct titration with standard acid, and the number of cubic centimetres of acid introduced directly into the equation. It has been found that when different alkalis are employed, their hydrolysing effect is proportional to their strengths, i.e. is due to the free hydroxyl ions. Different esters are hydro- lysed at very different rates by the same alkali; the rate appears to depend on the complexity of the molecule, i.e. the number of substituents present, and also on the nature of these substituents, viz. whether they are of a positive or negative nature. It has been found that CC1 3 C0 2 C 2 H 5 is hydrolysed by alcoholic potash much more readily than ethyl acetate itself, owing to the negative nature of the chlorine sub- stituents. (Compare A. 228, 257; 232, 103; J. C. S, 1899, 482.) In all cases it has been found that, comparing solutions of equal strength, e.g. N/10, a strong alkali is a much better hydrolysing agent than a strong acid. 2. A characteristic reaction of methyl and ethyl esters is that they exchange OMe^methoxy) or OEt (ethoxy) groups for NH 2 on treatment with strong ammonia, thus yielding acid amides, e.g. CH 3 CO-NH 2 . 3. Phosphorus pentachloride decomposes most esters, yield- ing an alkyl chloride and an acyl chloride, the of the OEt group being replaced by two chlorine atoms 4. Ethyl esters are readily transformed into methyl esters, R.COoEt >- R.C0 2 Me, by warming with methyl alcohol and a catalyst (CH 3 ONa, HC1). The reaction is reversible, and is termed alcoholysis. 5. Sodium methoxide combines with the esters to form un- (B480) M 178 VIL ACID DERIVATIVES x stable additive compounds, RC^-OCH,, which are derivatives ' of "ortho-acids". (See p. 142; also B. 20, 646.) The odour and taste of many of the esters is so agreeable that they are manufactured upon a large scale, and employed as fruit essences. Ethyl formate, H-CO.OC 2 H 5 , b.-pt. 55, is employed in the manufacture of artificial rum or arrak. Ethyl acetate, acetic ether, CH 3 .CO-OC 2 H r , b.-pt. 75, is used internally as a medicine. Amyl acetate, CH 3 - CO. OC 5 H n , b.-pt. 148. The alcoholic solution of this forms the essence of pears. Ethyl butyrate, CH 3 (CH. 7 ) 2 CO'OC 2 H 5 , is the essence of pine-apples. Iso-amyl iso-valerate, C 4 H 9 . CO OC 5 H n , b.-pt. 196, finds application as apple oil or apple ether. Cetyl palmitate, C 15 H 31 .CO.OC 16 H 33 , ceryl cerotate, C 2 ,H 51 CO OC 26 H 53 , and melissic palmitate, C 15 H 81 CO0C3Ji 6 j, are constituents of waxes. (See Wax Varieties, p. 158V) When the esters of the acids of high molecular weight are distilled under the ordinary pressure and not in a vacuum, they decompose into an olefine and a fatty acid. (See p. 46.) homers. All esters containing the same number of C atoms in the molecule, and derived from the monohydric saturated alcohols and the fatty acids, are isomeric. Thus methyl buty- rate is isomeric not only with ethyl propionate but also with propyl acetate' and with butyl formate. Further, all esters are isomeric with the monobasic acids which contain an equal number of carbon atoms, e.g. the esters just mentioned are isomeric with the valeric acids. (See Metamerism, p. 87.) Further cases of isomerism occur when the alcohol on the one hand, or the acid on the other, is unsaturated, e.g. allyl propionate and propyl acrylate. B. Acid Chlorides, Bromides, &e. Acid chlorides are the compounds derived from the acids by the replacement of the hydroxyl group by chlorine : B-CO-OH K-CO-C1. 1. They are usually prepared by the action of the chlo- rides of phosphorus, PC1 3 and PC1 5 , upon the acids or their salts : C 3 H r CO.OH4-PCl 5 = 0^.00-01 + POC1, + HCL ACID CHLORIDES 179 The acid chloric^ is separated from the POC1 3 formed at the same time by fractional distillation. In the case of acetic acid PC1 3 is conveniently used : 3CH 3 .CO.OH + PC1 3 = SCHg-CO-Cl + POaHg. Phosphorus oxychloride, POC1 3 , may also be allowed to act upon the alkali salts of the acids; when the latter are present in excess, acid anhydrides are produced (p. 180). Thionyl- chloride, SOC1 2 , and the acid are frequently used, as the only other product is S0 2 . 2. By the action of chlorine upon the aldehydes in the absence of water: CH 3 .CHO + C1 2 = CH 8 .COC1 + HC1. Properties. The acid chlorides are suffocating liquids which fume in the air, distil without decomposition, and are recon- verted by water, in many cases at the ordinary temperature, into the corresponding acids and hydrochloric acid : CHg.CO-Cl-f H 2 O = CH 3 .CO.OH-f HC1. They are thus more readily decomposed than the alkyl chlorides. When ,the chlorides are warmed with alcohols, the chlorine is replaced by alkyloxy groups, e.g. OCH 3 , OC 2 H 5 , and in this way esters are formed. With ammonia they yield acid amides, E.CO-NH 2 . With the sodium salts of the fatty acids they yield acid anhydrides. With organo-magnesium com- pound they first form ketones, and then tertiary alcohols (see p. 72). With silver cyanide acyl cyanides (e.g. CH 3 COCN, acetyl cyanide) are formed, and thfs^on hydrolysis with concentrated hydrochloric acid yield ketonic acids, CH 3 -CO- COOH. Formyl chloride is not known. Acetyl chloride (Ethanoyl chloride), CH 3 -COC1, is a mobile, colourless liquid of suffocating odour. Boils at 55, has a sp. gr. 1-13 at 0, reacts extremely vigorously with water and ammonium hydroxide, and is a reagent of exceptional im- portance, since it serves for the conversion of the alcohols and primary and secondary amines into their acetyl derivatives. It is thus frequently used for detecting OH, NH 2 or NH groups in organic compounds. The compound under exami- nation is heated with acetyl chloride (or even better, acetic anhydride), and the pure product either analysed or hydro- lysed, and acetic acid tested for in the products of hydrolysis (see p. 201). 180 VII. ACID DERIVATIVES The boiling-points of the acid chlorides are always con- siderably lower than those of the corresponding acids. Acid bromides and iodides are known and closely resemble the chlorides. Their boiling-points are higher. C. Acid Anhydrides ' Corresponding with the monobasic fatty acids there are ;^^^ hydrides, which may be regarded as derived from two molecul^M of the acid by the elimination of a molecule of water, e.g.; CH 3 .CO.OH _ CH 3 .CO\ ~ They may also be considered as acyl oxides. For instance, (CH 3 .CO) 2 = acetyl oxide. Preparation. 1. They cannot as a rule be obtained by the direct withdrawal of water from the acids, but by the action of acid chlorides upon the alkali salts of the acids: CH 3 .CO.;Ci + Na;O.CO.CH 3 = (CH 3 -CO) 2 O + NaCl. A very convenient method for preparing them is by the action of phosphorus oxychloride on the sodium salts of the acids, care being taken that sufficient of the dry sodium salt is used to decompose the acid chloride first formed (see p. 179) : = 2CH 3 -COC1 + NaCl + NaPO 3 . 2. By the action of phosgene on the acids (B. 17, 1286): 2CH 3 .CO.OH + COC1 2 = (CH 3 .CO) 2 + C0 2 3. The anhydrides of the higher acids are conveniently prepared by the action of acetic anhydride on their sodium salts. Properties. The majority of the acid anhydrides are liquids, but those of higher molecular weight solids, of neutral reaction, and soluble in alcohol and ether. They are non-miscible with water, but are gradually hydrolysed by it to the free acids. Dilute alkalis decompose them readily. When warmed with alcohols they yield esters; with ammonia, acid amides; and with hydrogen chloride, free acid and acid chloride: (CH 3 CO) 2 O + HC1 = CH 3 CO Cl + CH 3 CO OH. The boilin fir-point of an acid anhydride is higher than that THIO-ACIDS 181 of the corresponding acid, although an ether boils at a lower temperature than the corresponding alcohol, e.g. EtOH 78; Et 2 35; AcOH 118; Ac 2 137. Acetic anhydride, (CH 3 .CO) 2 0, is a mobile liquid of suffocat- ing odour, boiling at 137, and having a sp. gr. of 1*073 at 20. Like acetyl chloride it is a reagent of great importance, and largely made use of in testing for and estimating hydroxyl ups in carbon compounds, and for converting primary and ndary amines into acetyl derivatives. anhydrides containing two different acyl groups are TT also known (Gerhardt, Williamson), e.g. p, 2 ^ 3 n ^>0. When dis- tilled they yield the two simple anhydrides. Acyl peroxides have also been prepared. Acetyl peroxide, (C 2 H 3 0) 2 2 , is a thick liquid insoluble in water, which acts as a strong oxidizing agent and explodes when heated; it is prepared by the action of barium peroxide, Ba0 2 , upon acetic anhydride. Numerous other peroxides have been prepared recently by Baey&r and Tilliger (B. 1901, 34, 738) by means of hydrogen peroxide in the presence of potassium hydroxide. Among the simpler of these peroxides may be mentioned ethyl hydrogen peroxide, C 2 H 5 .0.0-H, a colourless liquid; diethyl peroxide, C 2 H 5 .0-O.C 2 H 5 , a liquid boiling at 65; acetone peroxide, (C 3 H 6 2 ) 2 , boiling at 132; and triacetone peroxide, (C 3 H 6 2 ) 3 , melting at 97. Many of these compounds are explosive. D. Thio-aeids and Thio-anhydrides Just as sulphur can replace oxygen in the alcohols and ethers, giving rise to mercaptans and alkyl sulphides, so it can replace oxygen in the carboxylic acids, giving rise to (1) R-CO-SH, thiolic acids; (2) R.CS-OH, thionic acids; and (3) R-CS-SH, thion-thiolic acids. Thiacetic acid (Ethane-tUolic add), CH 3 .CO.SH, is a colour- less liquid boiling below 100; it smells of acetic acid and sulphuretted hydrogen, and is readily decomposed by water into these two components. It is prepared from acetic acid and phosphorus pentasulphide, P 2 S 6 . The other thio-compounds are likewise readily hydrolysed, yielding acetic acid and hy- drogen sulphide. 182 VII. ACID DERIVATIVES E. Acid Amides and Hydrazides Amides. An acid amide is the compound derived from the acid by the introduction of the amido* group in place of the hydroxyl radical of the carboxylic group: E-CO-OH E-CO.NH 2 . They may also be regarded as derived from ammonia by-| the replacement of a hydrogen atom by an acyl group, e.g. ^ NH 2 CO CH 3 . Secondary and tertiary amides,' e.g. NH(CO CH 3 ) 2 , and N(COCH 3 ) 3 , are known, but are of relatively small importance. Modes of Formation. 1. By the dry distillation of the ammonium salts of the fatty acids: CH 3 .CO-ONH 4 = CH 3 .(X).NH 2 + H 2 O. 2. By addition of water to the alkyl cyanides (nitriles) : = CH 3 .CO.NH 2 . This addition of water is frequently effected by dissolving the nitrile in concentrated sulphuric acid, or in acetic and concentrated sulphuric acids, or by shaking with concentrated hydrochloric acid in the cold; also, and often quantitatively, by hydrogen peroxide, H 2 2 , in alkaline solution. In some cases a further addition of water occurs, and the ammonium salt of the acid is formed. 3. By the action of acid chlorides or acid anhydrides upon aqueous ammonia or solid ammonium carbonate; if amines are employed here, in place of ammonia, alkylated amides are formed: CH 3 .COCl-f2NH 3 = OE 3 .CONH 2 -J-NH 4 C1. 4. By heating esters with ammonia solution, sometimes even on shaking in the cold: CH 3 .CO-OC 2 H 6 + NH 3 = CH 3 .00-NH 2 -f C 2 H 6 OH. Properties. 1. With the exception of formamide they are colourless crystalline compounds, volatile without decomposi- tion, but with relatively high boiling-points. The following * The NH 4 group it usually termed an amino group when present in a primary amine, l>ut an amido group when present in an acid amide. ACID AMIDES 183 comparison of boiling-points is interesting, as the order is the same for most groups: Acetyl Ethyl Acetic Acetic chloride. acetate. acid. anhydride. Acetamide. Boiling-point 55 78 117 137 222 2. The lower members are soluble in water, and although derivatives of ammonia are, unlike most amines, practically neutral, the strongly positive character of the hydrogen atoms of the ammonia being cancelled by the entrance of the nega- tive acyl radical. Still, the primary amides are capable of forming additive compounds with some acids, e.g. acetamide yields the compound (C 2 H 3 NH 2 ) 2 HC1, "acetamide hydro- chloride"; these are, however, unstable, and are decomposed for the most part by water alone. On the other hand, the hydrogen of the amido group can be replaced by particular metals, especially mercury (also sodium; cf. B. 23, 3037; 28, 2353), the amides, therefore, playing the part of weak acids in the compounds so obtained, e.g. mercury acetamide, (CH 3 CONH) 2 Hg. 3. The amides are readily hydrolysed, more especially by alkalis, to the free acid and ammonia. Alkylated amides on hydrolysis yield the acid (or sodium salt) and an amine (not ammonia). Amines are not decomposed by alkalis. CH 3 .CO.NHC 2 H 5 + NaOH = CHg-CO-ONa + C 2 H 6 NH 2 . Hydrolysis of Acid Amides. The velocity of hydrolysis of the amides of the common fatty acids has been determined by Crocker and Lowe (J. C. S. 1907, 91, 593 and 952), using an electro-conductivity method. With sodium hydroxide and also hydrochloric acid, formamide is hydrolysed most readily, and valeramide least readily. 4. Nitrous acid converts the primary amides into the corre- sponding acids, with liberation of nitrogen : CH 3 .CO.NH 2 + N0 2 H = CHg-CO-OH + N, + H 2 O. This reaction is a general one, and corresponds exactly with the action of nitrous acid upon the primary amines (p. 108). 5. Nitriles (see p. 101) are formed by heating with P 4 10 , P 2 S 5 , and PC1 5 (see pp. 185 and 186). 6. If bromine in the presence of alkali is allowed to act upon primary amides, bromamides, BCONHBr, e.g. CH 3 - CO.NHBr, aceto-bromamide (colourless rectangular plates), are first formed, and these are decomposed by the alkali into 184 VII. ACID DERIVATIVES a primary amine, carbon dioxide and potassium hydroxide. If less bromine is used, urea derivatives are formed, e.g. methyl- acetyl-urea, CH 3 .NH.CO.NH.CO.CH 3 , which react with ex- cess of alkali, yielding primary amines in this case CH 3 NH 2 containing 1 atom of carbon less than the original amide. This is an excellent method for the preparation of amines from Cj to C 6 , but less valuable for those from C 6 onwards, as in the case of the higher compounds the production of amine diminishes, a nitrile being formed instead by the further action of the bromine (see below). Such nitriles C n H 2n+1 CN, in which n > 4, can therefore be obtained directly from the amine by the action of bromine and alkali upon it, thus : C 7 H 16 .CH 2 .NH 2 + 2Br 2 = CVH 15 .CH 2 .NBr 2 + 2HBr (Reversal of the Mendius reaction, p. 106; cf. Hofmann, B. 15, 407, 752; 17, 1407, 1920; 18, 2737.) Since these nitriles on hydrolysis yield acids containing 1 atom of carbon less than the amide originally taken, this reaction renders it possible to descend in the series successively from one acid to another (compare p. 160), e.g. : C H 13 .CH 2 .C0 2 H C 6 H 13 .CH 2 .CO.NH 2 C 6 H ir CH 2 .NH 2 C 6 H 13 .CH 2 .NBr 2 C 6 H 13 .CN C 6 H 13 .CO 2 H. This has been done in the case of the normal acids from C 14 to Cp and it furnishes a further proof of their normal con- stitution. Constitution. Most of the methods of formation and many of the properties of the amides point to the constitutional for- mula (I). A second formula is possible (II), in favour of which certain arguments have been adduced (B. 22, 3273; 23, 103; 25, 1435): (I) R.C (II) This last formula easily passes into the first by the migration of a hydrogen atom, and most of the reactions of the simple amides are explicable almost equally well by either formula. (Cf. Titherley, J. C. S. 1897, 468; 1901, 407.) We thus have a single compound which appears to possess, according to its reactions, two distinct formulae. Such a sub- stance is usually termed a tautomeric substance. AMIDO- AND IMIDO-CHLORIDES 185 On alkylation, under different conditions, it is possible to obtain two distinct types of mono-alkylated amides, viz.: and (n) These differ as regards physical and chemical properties; they are isomeric. Compounds of type I closely resemble the original amides; compounds of type II are usually known as imino ethers, and differ to a large extent (p. 187). In many other cases we find that a tautomeric substance gives rise to two distinct groups of alkyl derivatives (see Cyanogen Derivatives). Formamide (Methane-amide), HCO-NH 2 , is a liquid readily soluble in water and alcohol. It boils with partial decom- position at about 200. When quickly heated it decomposes into CO and NH 3 , and with phosphorus pentoxide it yields hydrocyanic acid. Acetamide, Ethane-amide, CH 3 -CO'NH 2 , forms long needles, readily soluble in water and alcohol. It melts at 82, boils at 222, and when pure has no odour. Di-acetamide, (C 2 H 3 0) 2 NH. M.-pt. 78; b.-pt. 223. HYDRAZIDES Just as ammonia by the introduction of acyl groups yields the acid amides, so hydrazine yields the acid hydrazides, e.g. acetyl hydrazine or acet-hydrazide, CH 3 CO NH NH 2 . They are formed by the action of esters on hydrazine. They are basic in character, are readily hydrolysed, and possess reduc- ing properties. With nitrous acid they yield acid azides, e.g. || , which are acyl derivatives of hydrazoic acid, , ^ || (N 3 H). All 4 hydrogen atoms in hydrazine can be replaced by acyl radicals in much the same manner as the 3 hydrogen atoms in the ammonia molecule can. The products are termed di-, tri-, and tetra-hydrazides, e.g. tetra-acet-hydrazide, Ac 2 N-NAc 2 . F. Amido-ehlorides and Imido-ehlorides By the action of PC1 5 upon the primary amides an ex- change of C1 2 for O takes place, giving rise in the first in- stance to the so-called amido-chlorides, e.g. acetdichloroamide, 186 VII. ACID DERIVATIVES CH 3 'CC1 2 NH 2 ; these are extremely unstable compounds, being converted by water into amide and hydrochloric acid, and readily giving up HC1, with formation of imido-chlorides, e.g. CH 3 CC1:NH, acetchloroimide. The imido-chloroides are also relatively unstable, yielding with water the amide and hydrochloric acid. When heated, they break up into nitrile and hydrochloric acid. The alkylated amides (p. 182) also yield chloroamides, e.g. CH 3 .CO.NH.C 2 H 5 gives CH 3 .CC1 2 .NH.C 2 H 5 , ethyl acet- chloroamide, and CH 3 .CO-NK 2 gives CH 3 .CC1 2 .NK 2 ; if these still contain amido-hydrogen, they readily yield imido- chlorides, e.g. CH 3 CC1:NC 2 H 5 , ethyl acetchioroimide. The chlorine in these compounds is chemically active; it can be exchanged for sulphur or for an amino group. G. Thiamides and Imido-thio-ethers Thiamides are compounds derived from the amides by the exchange of oxygen for sulphur, e.g. CHo'CS-NH 2 , thiacet- amide (ethane-thion-amide), CH 3 -CS'NHC 6 H 5 , thiacetanilide. They are mostly crystalline compounds, and result from the addition of H 2 S to the nitriles (CaJwurs), e.g.: = CH 3 .CS.NH 2 ; by treating acid amides with P 2 S 5 ; from the amido-chlorides, as given above; and by the action of H 2 S or CS 2 upon the amidines. Both simple and alkylated thiamides are known. When heated alone, they yield a nitrile and sulphuretted hydrogen (compare Elimination of Water from Amides). When hydrolysed with alkalis, they yield the corresponding acid, ammonia (amine) and H 2 S, thus: K.CS-NHR + 2H 2 o = K-CO-OH + H 2 s + NH 2 .R They are rather more acid in character than the amides, and thus many of them are soluble in alkali and yield metallic derivatives. Consequently, for them, as well as for the amides, the iso-formula R-C-TT is taken into consideration. From this pseudo form R'C^Mtn iso-thio acid amides, are derived a number of compounds, the Imino-thio -ethers, by the re- placement of one or both the hydrogen atoms by alkyl groups, AMtDlNttS 187 acetimido-thiomethyl, CH 3 .G< H S; methyl iso-thio-acet- QI /""'TIT iN 1. anilide, CH 3 C^-^ Q j| . They are decomposed by hydro- chloric acid into esters of thiacetic acid, thus: CH 3 .qNH).SCH 3 -f H 2 = CH 3 .CO.SCH S + NHg. These imino-thio-ethers are prepared by the action of mer- captans upon nitriles in presence of hydrochloric acid gas (Pinner), and by the action of alkyl iodides upon thiaraides (Wallach, Bernthsen)-. Imino-ethers, RC^-,, which are the oxygen compounds corresponding to the above imino-thio-ethers, and which are isomeric with the alkylated amides, are also known (Pinner), They are derived from the pseudo form of the acid amides, hypothetical compounds unknown in the free state, which are isomeric with the simple amides. They are formed by the combination of a nitrile with an alcohol under the influence of hydrochloric acid gas, and in certain cases by alkylating amides; some of them are liquids which boil with- out decomposition, but others are only known in the form of salts. H. Amidines Amidinesare compounds derived from the amides, R- CO 'NH 2 , R-CO-NHR', and R.CO-NR' 2 , by the replacement of oxygen by the bivalent imido-residue NH or (NR) : Acetamidine (ethane-amidine) Ethenyl-diphenyl amidine. The amidines are well-defined crystalline bases, and form stable salts. Like all acyl derivatives, they are readily hydro- lysed, and thus differ from the amines. Formation. I. By heating the amides with amines in pre- sence of PC1 3 (Hofmann) : H 2 O. 188 VIII. POLYSYDRIC ALCOHOLS 2. By treating the imido-chlorides, thiamides, and iso-thi- amides with ammonia or with primary or secondary amines (Wallach, Bernthseri), thus: = E-C(NH)(NHB') + H 2 S; = R-C(NH)(NH 2 ) + RSH. 3. By heating the nitriles with (primary or secondary) amine hydrochloride; this is a particularly easy method when aromatic amines are used, but not in the case of ammonium chloride (Bernthsen) : CH 3 .CN-f NH 2 .R = CH 3 .C(NH)(NHR). 4. By the action of amine bases or ammonia upon imino- ethers. Behaviour. 1. They decompose into ammonia or amine and acid when boiled with acids or alkalis (see above), and into ammonia and amide upon boiling with water. 2. The dry compounds, when heated, readily yield am- monia or amine and acid nitrile, so long as the imido-hydrogen atom has not been replaced by alkyl groups. Amidoximes are the compounds formed by the addition of hydroxylamine to nitriles, and, from this mode of formation and from their properties, appear to be amidines in which an amido- (imido-) hydrogen atom is replaced by hydroxyl: R.CN-f NH 2 OH = R.C Such an amidoxime is, for instance, isuret, NH 2 CH : N OH, also termed methenyl amidoxime, which is prepared from hydrocyanic acid and hydroxylamine; it is isomeric with carb- amide or urea; also ethenyl amidoxime, CH 3 'C(NOH)(NH 2 ). These compounds are hydrolysed in much the same manner as amidines. VIII. POLYHYDRIC ALCOHOLS A. Dihydric Alcohols or Glyeols, C n H 2n (OH) 2 The dihydric alcohols may be regarded as derived from the paraffins by the replacement of two hydrogen atoms by two hydroxyl groups. As the monohydric alcohols are often compared with the hydroxides derived from the monovalent jnetals, we may OLYCOLS 189 compare the glycols with the hydroxides derived from the bivalent metals, e.g. C 2 H 4 (OII) 2 with Pb(OH) 2 . In the satu- rated dihydric alcohols we have the hydroxyl groups attached to a bivalent alkylene radical, e.g. C 2 H 4 ", C 3 H ", &c. In many respects they resemble the monohydric alcohols, but they possess these properties in duplicate. Just as, e.g., plumbous hydroxide, Pb(OH) 2 , can give rise to two series of salts, e.g. the basic chloride, OH-Pb-Cl, and the normal chloride, PbCl 2 , so glycol, C 2 H 4 (OH) 2 , can give rise to two chlorides, OHC 2 H 4 .C1 and C 2 H 4 C1 2 , known respectively as glycol monochlorhydrin and glycol dichlorhydrin or ethylene dichloride. Similarly, with the acetates and amines derived from glycol we have OH.C 2 H 4 .O.CO.CH 3 and C 2 H 4 (O.CO.CH 3 ) 2 Mono-acetate Di-acetate, OH.C 2 H 4 .NH 2 and C 2 H 4 (NH 2 ) Hydroxyethylamine Ethylene diamine, and similarly with other glycols. The glycols, as alcohols, give rise to every class of alcoholic derivative; but when, for example, the formation of an ester such as glycollic monoacetate has taken place, this still behaves as a monohydric alcohol, yielding, e.g., with a second molecule of acid, a new ester; it is therefore termed an ester-alcohol. It is not necessary that both the groups which replace the hydrogen or hydroxyl should be of the same nature; thus we know a mixed derivative of the composition NH 2 C 2 H 4 S0 2 OH, which possesses at one and the same time the character of an amine and of a sulphonic acid. The glycols are mostly thick liquids of sweetish taste, a few only being solid crystalline compounds; they dissolve readily in water and alcohol, but are only sparingly soluble in ether. It will be found that the solubility of a compound in water tends to increase, and its solubility in ether to decrease, with the number of hydroxyl groups present in the molecule of the compound. Their boiling-points are much higher than those of the corresponding monohydric alcohols, just as these latter possess considerably higher boiling-points than the hydro- carbons from which they are derived. Constitution. As already stated, the glycols contain two hydroxyl groups in each molecule; the arguments in favour of the presence of these hydroxyl groups are exactly similar to those used in the study of the constitution of ethyl alcohol, 190 VIII. POLYHYDRIC ALCOHOLS and are btased mainly on certain methods of formation, and on the chief chemical characteristics of the compounds. Glycols which contain two hydroxyls linked to the same carbon atom are, as a rule, incapable of existence, and are only known in derivatives (see p. 64). Instead of the glycols CH 2 (OH) 2 and CH 3 -CH(OH) 2 , we always obtain the corre- sponding aldehydes, CH 2 : and CH 3 CH : O. All glycols con- tain their hydroxyls attached to two different carbon atoms. Glycol itself has thus the constitution OH CH 2 CH 2 OH, which can be proved directly by transforming it, by means of hydrochloric acid, into glycol chlorhydrin, CH 9 C1 CH 2 OH, and oxidizing the latter to monochloracetic acid, Cll 2 Cl CO OH. In this last compound the chlorine and hydroxyl are united to different carbon atoms, and consequently the same applies to glycol chlorhydrin and to the two hydroxyl groups of glycol. (Cf. p. 62.) The monohydric alcohols are distinguished as primary, secondary, and tertiary. The glycols may in the same way be characterized as di-primary when they contain the group CH 2 OH twice, as in glycol; as primary- secondary when they contain the group CH 2 'OH together with the group CHOH, as in propylene glycol, CH 3 .CH(OH) CH 2 OH; further as di-secondary, primary-tertiary, secondary-tertiary, and di- tertiary. The structure of a glycol is usually determined by an examination of its oxidation products. (See pp. 192, 203, et seq.) Modes of Formation. 1. From the di- halogen -substituted derivatives of the paraffins, in which the two halogen atoms are attached to two different carbon atoms, e.g. ethylene bromide: (a) By transformation into the di-acetates by means of silver or potassium acetate, and hydrolysis of the ester so produced by potash or baryta water: CH 2 Br CH 2 Br -f 2 CH 3 CO O Ag = CH 3 .CO.O.CH 2 .CH 2 .O.CO.CH 3 4-2AgBr, GH 3 .CO.O.CH 2 .CH 2 .0.(X).CH 3 = OH.CH 2 .CH 2 -OH + 2CH 3 .COOK. In the actual preparation of glycol from ethylene bromide, potassium acetate and alcohol (Demole), this saponification ensues directly upon prolonged boiling of the mixture. (b) By boiling with water and lead oxide or potassium carbonate. These reagents serve to neutralize the acid as it is formed, and so the reaction is facilitated: ^-f 2HOH ^ C 2 H 4 (OH) 2 + 2HBr. PROPERTIES OF GLYCOLS 191 2. In the reduction of ketones to secondary alcohols, the so-called pinacones, i.e. di-tertiary glycols, are obtained as by- products (see pp. 72 and 134), thus: CMe 2 :0 CMe 2 .OH -f 2H = . (pmacone). CMe 2 :O CMe 2 .OH * 3. By the careful oxidation of olefines by means of very dilute KMn0 4 (p.. 45): CH 2 :CH 2 + O + H 2 O = OH.CH 2 .CH 2 .OH. Behaviour. 1. As in the case of the monohydric alcohols, the hydrogen of the hydroxylic groups is directly replaceable by potassium or sodium, with the formation of alcoholates, e.g. OH C 2 H 4 ONa and C 2 H 4 (ONa) 2 , sodium and di-sodium glycols. 2. The metal in these compounds may be exchanged for new alkyl groups by treatment with alkyl iodide, when gly- collic ethers are obtained: C 2 H 4 (ONa) 2 + 2C 2 H 6 I = Glycol di-ethyl ether. These ethers, like those of the monohydric alcohols, are stable, and cannot be hydrolysed by dilute mineral acids or alkalis. 3. Acids act upon them to produce esters, which are either normal esters or ester-alcohols (see p. 189). The halogen esters of the glycols are termed chlor-, brom-, or iodhydrins, e.g. glycol chlorhydrin, C 2 H 4 C1(OH), glycol di- chlorhydrin, C 2 H 4 C1 2 , &c. The ester-alcohols which are formed by the action of halogen hydride may also be regarded as mono-substitution products of the monohydric alcohols, which cannot be prepared by direct chlorination, e.g. C 2 H 4 C1(OH), monochlorethyl alcohol. Similarly the di- halogen esters, CHgCl-CHgCl, CH 2 Br.CH 2 Br, &c., are the di-substitution pro- ducts of the paraffins, viz. ethylene dichloride and dibromide. 4. As the halogen atoms in the chlor-, brom-, and iodhy- drins are readily replaceable, just as in C 2 H 5 C1 or C 2 H 5 I, these compounds may be used for the preparation of most of the other glycol derivatives; thus they yield thio-glycols with potassium hydrosulphide, amines with ammonia, sulphonic acids with sodic bisulphite, and nitriles with potassic cyanide. 5. Alkalis react with the glycol monochlorhydrins, and by the elimination of HC1 yield cyclic anhydrides, e.g. ethylene PTT oxide, 2 J>0. It is interesting to note that these anhydrides CJBL/ 192 VIII. POLYHYDRIC ALCOHOLS cannot be obtained by the elimination of water from the glycols themselves. When ethylene glycol is heated with zinc chloride at 230 water is eliminated, and the product obtained is acet- aldehyde (or a polymer). This reaction is explained by assum- ing the intermediate formation of unsaturated alcohols which are not in themselves capable of existence, e.g. CH 2 :CH(OH), but which immediately undergo transformation into the iso- meric aldehydes or ketones: CH 2 :CH.OH = CH 3 -CH:O. 6. As alcohols the glycols are readily oxidized. If they contain the primary alcoholic group, they can yield aldehydes and acids containing the same number of carbon atoms. If they contain a secondary alcoholic group, they yield ketones, e.g. : CH 2 OH.CH 2 OH CHO.CH 2 OH and COOH.CH 2 OH COOH-COOH CH 3 .CH(OH).CH 2 OH > CH 3 .CH(OH).COOH CH 3 .CO.COOH, &c. Methylene- and Ethylidene-glycols. (See Aldehydes.) Ethylene glycol (glycol), OH.CH 2 .CH 2 .OH (Wurtz, A. 100, 110), is prepared from ethylene bromide by means of potas- sium acetate in alcoholic solution (Demole), or of potassium carbonate in aqueous solution, as given above (A. 192, 250). For properties, see above. Its formula has been corroborated by the determination of its vapour density. Oxidizing agents transform it into gly collie acid, OH CH 2 CO OH, and oxalic acid, OH- CO- CO- OH. Propylene glycol is known in two isomeric forms, viz. : (a) Trimethylene glycol, /3-Propylene glycol, Propa7ie-l:3- diol, OH-CHg.CH^.CHg.OH, which is prepared from tri- methylene bromide, and is a di-primary glycol boiling at 216. It is also produced by the Schizomycetes fermentation of gly- cerol (B. 14, 2270). (b) a-Propylene glycol, Propane - 1 : 2 - diol, CH 3 -CH(OH). CH 2 OH, can be prepared from propylene bromide in an analogous manner, but is more easily obtained by distilling glycerol with caustic soda. It boils at 188. It contains an asymmetric carbon atom in the molecule, and becomes opti- cally ( ) active when fermented, i.e. fission fungi destroy the dextro modification more rapidly than the laevo. DERIVATIVES OF GLYCOLS 193 Four butylene glycols, and various amylene- and hexylene- glycols, &c., are also known. Of these, the y-glycols (in which the hydroxyls are in the positions 1:4, and which therefore contain the grouping G(OH) C C C(OH) ) yield compounds of the furane series by the formation of anhydrides (B. 22, 2567), and therefore stand in close relation to thiophene and pyrrole. Pinacone, Tetramethyl - ethylene glycol (2:3- Dimethyl - butane-2:3-diol), (CH 3 ) 2 : C(OH) C(OH) : (CH 3 ) 2 . The hydrate, (+ 6H 2 0), forms large quadratic tables; in the anhydrous state it is a crystalline mass melting at 38 and boiling at 172. When warmed with dilute sulphuric or hydrochloric acid it yields pinacoline, CH 3 CO C(CH 3 ) 3 , methyl tertiary- butyl ketone or 2:2-dimethyl-butan-3-one (see p. 137): In this reaction. an interesting intramolecular rearrangement occurs, together with the elimination of water. Numerous other pinacones are known. They may be ob- tained by reducing ketones or synthetically (Lieben, M. 17, 68; 19, 16), and with acids yield the corresponding pinacolines. DERIVATIVES OF THE GLYCOLS The ethers, e.g. C 2 H 4 (OCH 3 ) 2 , are mostly colourless liquids with ethereal odours, and have lower boiling-points than the glycols. (Cf. Ether and Ethyl Alcohol.) They cannot be readily hydrolysed. The esters, e.g. C 2 H 4 (0 CO CH 8 ) 2 , are also mostly liquids, and are readily hydrolysed. The following esters of inorganic acids are interesting: Glycol chlorhydrin, CH 2 C1.CH 2 -OH, obtained by passing hydrogen chloride into warm glycol, or by the addition of hypochlorous acid to ethylene, is a liquid miscible with water, and boiling at 130; in this last respect differing from its corre- sponding alcohol to almost the same extent as ethyl chloride does from alcohol. Glycollic di-nitrate, CoH 4 (N0 8 ) 2 , is prepared by acting on glycol with sulphuric and nitric acids: C 2 H 4 (OH) 2 + 2N0 2 .OH = C 2 H 4 (0-N0 2 ) 2 + 2H 2 O. It is a yellowish liquid, insoluble in water, is readily hydro- (3480) N 194 VIII. POLYHYDRIO ALCOHOLS lysed by alkalis to glycol and nitric acid, and hence the con- stitution. The formation of such nitric esters, which are highly explosive, is characteristic of the polyhydric alcohols (see Nitroglycerine). Ethylene cyanide, CN CH 2 CH 2 ON, obtained by the action of potassium cyanide on ethylene dibromide, is a crystalline solid, and on hydrolysis with alkalis yields CO 2 H CH 2 CH 2 C0 2 H, succinic acid, and hence may be regarded as succinonitrile. Glycol monochlorhydrin with potassium cyanide yields ethylene cyanhydrin, or the nitrile of /3-lactic acid, OHCH 2 . CH 2 CN. Isomeric with it is ethylidene cyanhydrin, CH 3 CH(OH)CN, the additive product of hydrocyanic acid and aldehyde (p. 126). Ethylene oxide, C 2 H 4 (Wurtz\ obtained by distilling glycol chlorhydrin with caustic -potash solution, is a mobile liquid of ethereal odour boiling at 13 -5. It is miscible with water, and slowly converted into the glycol. It has many of the properties of an unsaturated compound, e.g. with HC1 it yields the chlorhydrin, with NH 8 the amino alcohol, OH.CHg.CHg.NH^ and with chlorine ethylene di- chloride. It is largely owing to the last reaction that the ring consti- s. tution, i-. /O, and not the open-chain formula, CH 2 :CHOH, CHy is given to the compound. The formation of additive com- pounds is accompanied by the rupture of the ring. Some of the higher homologues of ethylene oxide are much more stable, and do not yield additive compounds; this is due to the fact that the ring is more stable and therefore less easy to rupture (compare Polymethylene Compounds). AMINES OF THE DIHYDRIO ALCOHOLS These are derived from glycols by the replacement of one or both hydroxyl groups by amino groups : OH.CH 2 .CH 2 .NH 2 and NH 2 .CH 2 .CH 2 -NH 2 Hydroxy ethylamine Ethylene diamine. In the former case compounds are obtained wnich possess the properties of an amine in addition to those of an alcohol; in the latter, diamines free from oxygen, which are analogous to ethylamine, but are di-acid and not mono-acid bases. DIAMINES 195 Secondary and tertiary diamines corresponding with the primary amiiie, NH 2 -CH 2 .CH 2 .NH 2 , are known, e.g.: The methods by means of which these diamines can be obtained are analogous to those described for the monamines, viz. : 1. By heating ethylene bromide, &c., with alcoholic am- monia to 100 (Hofmanri): C 2 H 4 Br 2 + 2NH 3 = C 2 H 4 (NH 2 ) 2 + 2HBr; C 2 H 4 (NH 2 ) 2 + C 2 H 4 Br 2 = (C 2 H 4 ) 2 N 2 H 2 + 2HBr; (C 2 H 4 ) 2 N 2 H 2 + C 2 H 4 Br 2 = (CgH^N, + 2HBr. The primary, secondary, and tertiary bases, which are formed simultaneously, can be separated by fractional distillation. The hydroxy amines (or alkines, Ladenburg) are obtained in an analogous manner by using ethylene chlorhydrin, thus: C 2 H 4 (OH)C1 -f NH 3 In this case also primary, secondary, and tertiary bases are produced at the same time, and are separated by the fractional crystallization either of their hydrochlorides or of their platini- chlorides. Ethylene chlorhydrin yields choline chloride (p. 196) with trimethylamine. 2. Primary diamines are formed by the reduction of the nitriles, C n H 2n (CN) a , e.g. by adding metallic sodium to the hot alcoholic solution: CN.CH 2 .CH 2 .CN-f 8H Butylene diaraine. Ethylene diamine, C 2 H 4 (NH 2 ) 2 , Diethylene diamine, (C 2 H 4 ) 2 N 2 H 2 , &c., are colourless liquids distilling without de- composition. The former boils at 123, and has an ammoni- acal odour; the latter melts at 104 and boils at 146, and is identical with piperazine, i.e. hexahydro-pyrazine. Hence /~ITT r^TT it possesses the constitutional formula NH<^QTT 2 ^Tr^NH, and has a closed-chain constitution (Hofmann, B. 23, 3297). Tetr amethylene - diamine, Butane -1:4- diamine, putrescine, butylene-diamine, NH 2 CH 2 CH 2 CH 2 CH 2 . NH 2 , is prepared according to method 2, and is also formed during the putre- 196 VIII. POLYHYDRIC ALCOHOLS faction of flesh. As a " y-diamine ", i.e. the diamine of a y-glycol, it is closely related to pyrrole, from which it is formed by the action of hydroxylamine (whereby a dioxime is first produced), and subsequent reduction (B. 22, 1968). Pentamethylene diamine, cadaverine, NH 2 (CHA'NHo, is formed by the reduction of trimethylene cyanide, CN (CH 2 ) 3 CN, which on its part is prepared from trimethylene bromide CH 2 Br.CH 2 .CH 2 Br, and KCN (Ladenburg). It is a colourless syrupy liquid of very pronounced spermaceti and piperidirie odour, solidifies in the cold, and boils at 178-179. It possesses especial interest, because, being a S-diamine, it gives up ammonia CH CH and yields the cyclic base piperidine, C ' (see this). Many of these poly acid bases are found in decaying albumen and in corpses, and are designated ptomaines or toxines (cf e.g. B. 19, 2585). Choline, bilineurine, ethykl - trimethyl - ammonium hydroxide, OH.CH 2 .CH 2 .NMe 3 .OH (Strecker), is found in the bile (x^?> bile), brain, yolk of egg, &c., being present in these combined with fatty acids and gly eery 1- phosphoric acid as lecithin. It is also found in herring brine, hops, beer, and in many fungi, &c., and is obtained by boiling sinapine with alkalis (the old name for this product was " Sincaline "). Choline is a strong, deliquescent base, and readily absorbs carbon dioxide from the air. It is not poisonous. The chloride has the formula OH 'CoH^NMegCl. Concentrated HN0 3 oxidizes choline to muscarine, C 5 H 15 N0 3 = (OH) 2 CH- CH 2 NMe a OH, an excessively poisonous base, which is present in toad-stool, Agaricus muscarius. By transforming choline, by means of hydriodic acid, into its iodide, CH 2 I-CH 2 'NMe 3 I, and treating the latter with moist oxide of silver, and also from the putrefaction of choline, neurine (vevpov, nerve), trimethyl -vinyl -ammonium hydroxide, CH 2 :CHNMe 3 -OH (Hofmann), is obtained. This base, con- taining the unsaturated radical " vinyl ", C 2 H 3 , is very similar to choline, and can also be prepared from brain substance; it is only known in solution, and is very poisonous. It can be re-transformed into choline. (For this, and also for deriva- tives, see e.g. A. 267, 249; 268.) Another natural compound related to hydroxy ethylamine is taurine, C 2 H 7 NS0 3 (Gmelin), which is present in combina- tion with choljc acid as tauroeholic acid in the bile of oxen TRIHYDRIC ALCOttOLS 19? and many other animals, also in the kidneys, lungs, &c. It crystallizes in large monoclinic prisms, is readily soluble in hot water, but insoluble in alcohol, and decomposes when strongly heated. Its constitution follows from its synthesis. Isethionic acid, hydroxy-ethyl-sulphonic acid, OH GEL* CH 2 S0 2 OH, is obtained when carbyl sulphate, C 2 H 4 S 2 6 (from C 2 H 4 and S0 3 ), is boiled with water; its constitution follows from its properties, and also from the fact that it may be obtained by the oxidation of the hydroxymercaptan, OH-CH^CEL-SH. Isethionic acid with PC1 5 yields the chloride CH 2 C1 CH 2 S0 2 C1, and this with water gives chloro- ethyl-sulphonic acid, CH 2 C1 CH 2 S0 2 OH, which with am- monia yields taurine; its constitution must, therefore, be NH 2 .CH 2 .CH 2 -S0 2 .OH, amino-ethyl-sulphonic acid, and in accordance with this constitution it unites in itself the pro- perties of an alcoholic amine and a sulphonic acid, and is therefore at the same time a base and an acid. It forms unstable salts with alkalis, but not with acids, the groups NH 2 and S0 3 H in the molecule practically neutralizing one another, so that its reaction is neutral. Nitrous acid converts it into isethionic acid, a reaction analogous to the decom- position of the primary amines by this reagent. As an alky 1 sulphonic acid, it is not hydrolysed by boiling with alkalis and acids. It is sometimes represented as a cyclic ammonium salt, CH 2 .NH 3 CH 2 -SO 3 . B. Trihydric Alcohols The molecule of each trihydric alcohol contains three hy- droxyl groups, each attached to a different carbon atom. They may be regarded as analogous to the hydroxides of tervalent meteU e.g. C S H 6 (OH) 8 arid A1(OH) 3 . They can give rise to three distinct groups of derivatives according as one, two, or three of the hydroxyls react, e.g. chlorides C 3 H 5 C1(OH) 2 , monochlorhydrin; C 3 H 5 C1 2 -OH, dichlorhydrin; and C 3 H 5 C1 3 , trichlorhydrin of glycerol. Similarly for acetates, amino- derivatives, &c. Although the compound CH(OH) 3 , ortho-formic acid, is not known, derivatives, e.g. ethyl ortho-formate, CH(OEt) 3 , (p. 142), and similarly ethyl ortho-acetate, CH 8 -C(OEt)3, can readily be prepared. 19$ Vtlt. fOLYHYDHIC ALCOHOLS Glycerine, glycerol, propane-I:2:3-triol, OH CH 2 . CH(OH) CH 2 -OH. (Scheek, 1779; formula established by Pelouze in 1836, and constitution by Berthelot and Wurtz.) Synthesis. By heating 1 : 2 : 3-trichlorpropane with water tc 170: CH 2 C1 CH 2 .OH CHC1 +3H-OH = CH-OH + 3HC1. CH 2 C1 CH 2 .OH The trichlorpropane is itself obtainable from isopropyl iodide (which can also be prepared synthetically) by conversion into propylene, addition of C1 2 , and heating the propylene dichloride thus formed with iodine chloride (Friedel and Silva, Bull. Soc. Chim. 20, 98): CH 3 .CHI.CH 3 CH 3 .CH:CH 2 CH 3 .CHC1-CH 2 C1 CH 2 C1.CHC1.CH 2 C1. Glycerol is also produced when allyl alcohol is oxidized with very dilute potassium permanganate : CH 2 :CH-CH 2 .OH OH.CH 2 .CH(OH).CH 2 .OH. The constitution of glycerol follows from these syntheses and also from its relation to tartronic acid (p. 199); each of the three hydroxyls is attached to a separate carbon atom. Preparation. Glycerol is usually prepared by hydrolysing the natural fats and oils (especially olive-oil), which are the glyceryl salts of fatty and other acids (p. 158). The hydro- lysis may be effected by means of superheated steam, by heating with lime and water, or with sulphuric acid. They are thus resolved into their components, glycerol and acid; the glycerol distils over with the superheated steam, and may be purified by animal charcoal. Hydrolysis by means of an enzyme contained in castor-oil seeds is used commercially. In the manufacture of stearic acid (p. 161) the fats are hydrolysed with sulphuric acid, when the glycerol is con- verted into glyceryl-sulphuric acid, C 3 H 5 (OH) 2 (0*S0 3 H), from which it can be obtained by boiling with water or with lime. In the preparation of plaister, by boiling fats with lead oxide and water (p. 160), an aqueous solution of glycerol is obtained together with the insoluble lead plaister. Large quantities of glycerol are now recovered from the liquors from which the hard soaps (p. 158) have separated. Properties. It is a thick, colourless syrup, of specific gravity GLYCEROL 199 1-27, solidifies, when strongly cooled, to crystals like those of sugar-candy, which melt at 17. It boils at 290, but, when impure, can be distilled without decomposition under diminished pressure only, viz. at 170 under 12 mm. It is very hygro- scopic, and mixes with water and alcohol in all proportions, but is insoluble in ether. Uses. In the manufacture of liqueurs, fruit preserves, wine, &c.; for non-drying stamp colours and blacking; when mixed with glue, in book printing; as a healing ointment for external use; but especially in the manufacture of nitro-glycerine and in the colour industry. Behaviour. 1. With alkalis and other metallic hydroxides it forms alcoholates, which are readily decomposed again into their components. 2. As a trihydric alcohol the hydrogen atoms of the OH groups can be replaced by alkyl radicals yielding ethers, e.g. mono-ethylin, C 3 H 5 (OH) 2 (OC 2 H 5 ),and triethylin, C 3 H 5 (OC 2 H 5 ) 3 , liquids which boil without decomposition. 3. As an alcohol it forms the most various esters : thus, with sulphuric acid, the easily saponifiable glyceryl-sulphuric acid, C 3 H 5 (OH) 2 (0 S0 3 H); with phosphoric acid, glyceryl-phosphoric acid, C 3 H 5 (OH) 2 (O.P0 3 H 2 ); with nitric acid, glyceryl trini- trate, C 3 H^(0'N0 2 ) 3 ; with hydrochloric acid the chlornydrins ; and with the higher fatty acids the fats. For its behaviour with hydriodic acid, or iodine and phosphorus, see p. 60. 4. It yields compounds of a mercaptan or aminic character by exchange of OH for SlTor NH 2 . 5. When distilled with dehydrating agents, e.g. phosphorus pentoxide, or, better, anhydrous potassium hydrogen sulphate, two molecules of water are eliminated from each molecule of glycerol, and acrolein (p. 130) is formed. By the indirect sepa- ration of one mol. H 2 0, glycide alcohol, C 3 H 6 2 , is obtained. 6. Oxidizing agents convert it, according to circumstances, either into glyceric, OH CH 2 . CH(OH) . C0 2 5, tartronic, C0 2 H.CH(OH).C0 2 H, or mesoxalic acid, C0 2 JB^ CO . CO JEt, or acids with a smaller number of carbon atoms. The for- mation of the three above-mentioned acids indicates that glycerol molecule must be built up of two primary and one secondary alcoholic groups, as represented in the formula already given. Halogens oxidize and do not substitute. 7. It yields 'normal butyl alcohol, caproic acid, and butyric acid by certain fermentations. (Cf. B. 16^ 884.) 8. It is largely used in the preparation of allyl alcohol (p. 82), 200 VIII. POLYttYDRIC ALCOHOLS acrolein (p. 130), allyl iodide (p. 65), isopropyl iodide (p. 60), and formic acid (p. 148). DERIVATIVES Chlorhydrins (hydrochloric esters). Mono- and dichlor- hy drills are formed by the action of hydrochloric acid on glycerol, and trichlorhydrin by the action of phosphorus pentachloride on the mono- or di-compounds. Each of the two first-named exists in two isomeric modifications. a-Monochlorhydrin, S-Chloro-propane-l-.Z-diol, CH 2 (OH)' CH(OH).CH 2 C1, is formed from epichlorhydrin, C 3 H 5 O.C1, (see below), and water; a-dichlorhydrin, I:3-dichloro-propane-2-ol, CH 2 C1 CH(OH) . CH 2 C1, from epichlorhydrin and HC1; /3-mono- chlorhydrin, CH 2 (OH).CHC1-CH 2 (OH), and ^-dichlorhydrin, CH 2 C1.CHC1-CH 2 .OH, by the addition of hypochlorous acid to allyl alcohol or to allyl chloride. The chlorhydrins are liquids sparingly soluble in water, and readily soluble in alcohol and ether. Their boiling-points are much below that of glycerol. Glycide Compounds. By the elimination of water from glycerol a compound is obtained which unites within itself the properties of ethylene oxide and of a monohydric alcohol, viz. glycide alcohol, OH-CHjj.CH.OH OH.CH 2 .CH\ CHj-OH " CH2/' which is isomeric with propionic acid. It may be prepared by the abstraction of HC1 from a-mono- chlorhydrin by means of baryta, just as ethylene chlorhydrin yields ethylene oxide. It is a colourless liquid, boiling at 162, and miscible with water, alcohol, and ether. It combines with H 2 0, yielding glycerol, and with HC1 yielding the chlorhydrin, and, as an alcohol, forms esters (glycide esters), &c. Its hydro- chloric ester is epichlorhydrin, CH 2 C1- isomeric with chlor-acetone and propiony) chloride, a mobile liquid of chloroform odour, boiling at 117, which is formed by the elimination of HC1 from either of the dichlorhydrins. Like ethylene oxide it is capable of combining with ELO, HC1, &c. Esters of Nitric Acid. Mononitrin, C 3 H 6 (OH) 2 (O POLYHYDRIC ALCOHOLS 201 and trinitrin or nitre-glycerine, C 3 H 5 (0'N0 2 ) 3 , are known. The latter is prepared by treating glycerol with a cold mix- ture of concentrated nitric and sulphuric acids (B. 1899, 32, 1444). It is a colourless oil, insoluble in water, poisonous, and of a sweet, burning, aromatic taste. Sp. gr. 1*6. M.-pt. about 11-12. It burns without explosion, but explodes with terrible violence when quickly heated or when struck (Nulel's explosive oil). When mixed with kieselguhr in the proportion of three parts to one it forms dynamite (Nobel, 1867), which is exploded by fulminate of mercury with frightful force. It is hydrolysed by alkalis and by ammonium sulphide, yielding glycerol and nitric acid, and hence its constitution as a nitrate, 3 H 5 (0 N0 2 ) 3 , and not a nitro-derivative, e.g. C 3 H 2 (N0 2 ) 3 (OH) 3 . The esters derived from glycerol and the fatty acids are largely met with in vegetable and animal oils and fats. Most of these are the normal esters, e.g. glyceryl tripalmitate, tripal- mitin, C 3 H 5 (0 CO C 15 H 31 ) 3 , tristearin, &c. (see p. 158, et seq.). These esters can also be obtained artificially, as can also the mono- arid dihydric esters, e.g. monopalmitin, (OH) 2 C 3 H 5 .O CO.C 15 H 31 , and dipalmitin, OH . C 3 H 5 (0 CO C 15 H 31 ) 2 . Most are wax-like solids, and, on hydrolysis, yield as ulti- mate products glycerol and the fatty acid. With the normal esters this hydrolysis occurs in stages yielding the mono- hydroxy ester, then the dihydroxy, and finally glycerol. C. Tetra-, Penta-, and Hexahydric Alcohols These alcohols can react respectively with 4, 5, or 6 mole- cules of a monobasic acid to form neutral esters, and conse- quently 4, 5, or 6 alcoholic hydroxyls are to be assumed as present in their molecules. The number of hydroxyls present in an alcohol is usually determined from the number of acetyl groups present in the ester which is formed when the alcohol is heated with acetic anhydride and anhydrous sodic acetate, thus: C 6 H 8 (OH) 6 + 6(CH 3 .CO) 2 = C 6 H 8 (0-CO.CH 3 ) 6 + 6CH..CO.H. One of the simplest methods of determining the number of acetyl groups is to hydrolyse the acetate by distilling with ben- zene sulphonic acid in steam, and to titrate the acetic acid in the distillate with standard barium hydroxide, using phenol- phthalein as indicator (Sudborough and Thomas, J. C. S. 1905, 1752). 202 VIII. POLYHYDRIC ALCOHOLS The ester of any alcohol in question may also be prepared by the aid of an acid containing halogen, bromo-benzoic acid being especially suitable for this; and from the percentage of bromine found in the ester, the number of acid radicals which have entered the molecule, i.e. the number of hydroxyls, can be deduced. The polyhydric alcohols are solid crystalline compounds of sweet taste. Many occur as natural products, and they may be obtained by the reduction of the corresponding hydroxy aldehydes, hydroxy ketones, or hydroxy monobasic acids (man- nonic acid, &c.) by sodium amalgam. (E. Fischer, B. 22, 2204.) Conversely, cautious oxidation by bromine water transforms them first into sugars (hydroxy aldehydes), and then into the corresponding acids. As a rule they cannot be volatilized without decomposition. Their derivatives are exactly analo- gous to those of glycol and glycerol. Their constitution follows from the generalization already repeatedly referred to, viz. that not more than one hydroxyl group can be attached to the same carbon atom without the immediate separation of water, so that a tetrahydric alcohol must contain at least 4, and a hexahydric alcohol at least 6, atoms of carbon. The tetrahydric alcohol erythritol, C 4 H 6 (OH) 4 , has thus the formula: OH CH 2 CH(OH) CH(OH) CH 2 OH, and mannitol, the simplest of the hexahydric alcohols, C 6 H 8 (OH) 6 , the formula: OH.CH 2 (CH.OH) 4 .CH 2 .OH. All the common polyhydric alcohols have a normal carbon chain, as on reduction with hydriodic acid they yield normal secondary iodides, e.g. erythritol yields 2-iodo-butane, CH 3 - CHI.CH 2 .CH 3 . 1. Tetrahydric Alcohols. Ortho-carbonic ether, C(OC 2 HJ 4 , is to be regarded as the ether of the hypothetical alcohol, C(OH) 4 , which may be looked upon as the hydrate of carbonic acid, but is itself incapable of existence. It is a liquid of ethereal odour, boiling at 159. Erythritol (Butane-tetrol) occurs in the free state in Proto- coccus vulgaris, and combined with orsellinic acid as an ester (erythrin), in many lichens and algas. It forms large quad- ratic crystals, sparingly soluble in alcohol arid insoluble in ether. M.-pt. 112; b.-pt. about 300. 2. Pentahydric Alcohols, Arabitol, OH . CH 2 . (CH - OH) 3 . HEXAHYD&IC ALCOttOLS 203 CH 2 OH (from arabinose by reduction). Xylitol, by the reduction of xylose, is stereo - isomeric ; and rhamnitol, OH CH 2 (CH . OH) 4 . CH 8 , m.-pt. 121, from rhamnose, is homologous. 3. Hexahydric Alcohols, Mannitol, OH.CH 2 .(CH.OH) 4 . CH 2 OH (Proust, 1800), is found in many plants, for instance in the larch, in Viburnum Opulus, in celery, in the leaves of Syringa vulgaris, in sugar-cane, in Agaricus integer (of the dry substance of which it forms 20 per cent), in rye bread, and especially in the manna ash, Fraxinus ornus, the dried juice of which constitutes manna. It can be prepared from grape- sugar, or still better from fruit sugar, from which it only differs in composition by containing two atoms of hydrogen more in the molecule, by reduction with sodium amalgam. It crystallizes in fine needles or rhombic prisms, and is readily soluble in cold water and boiling alcohol. It is dextro-rotatory, but a laevo-rotatory and an inactive modi- fication are also known. (See Mannonic Acid.) M.-pt. 166. When heated it is converted into its anhydrides, mannitan, C 6 H 12 5 , and mannide, C 6 H 10 4 . Cautious oxidation converts mannitol into a mixture of mannose, OH CH 2 (CH OH) 4 CHO, and fructose, OH.CH 2 (CH.OH) 3 .CO.CH 2 .OH. Nitric acid oxidizes it to saccharic acid, C0 2 H . (CH OH) 4 COJE ; hydri- odic reduces it to secondary hexyl iodide, CH 3 CHI (CH 2 ) 3 CH 8 (p. 59). The molecule of mannitol contains 4 asymmetric carbon atoms, e.g. : OH.CH 2 .CH(OH).CH(OH).CH(OH).OH(OH).CH 2 OH, and hence a number of stereo-isomerides are known, e.g. d-, 1-, and r-mannitol, d-, 1-, ?--sorbitol, and dulcitol, which is optically inactive owing to the fact that its molecule is symmetrical in configuration. (See Stereochemistry of the Sugars.) The sugars are closely related to the penta- and hexa- hydric alcohols, being the corresponding polyhydric aldehydes or ketones. The alcohols as a rule are not fermented by yeast, and do not reduce an alkaline cupric solution, dulcitol excepted. OXIDATION PRODUCTS OF THE POLYHYDRIC ALCOHOLS Just as the monohydric alcohols are oxidized to aldehydes, ketones, and acids, so the polyhydric alcohols pass, on oxida- tion, into aldehydes, ketones, and polybasic acids. 204 VIII. POLYHYDRIC ALCOHOLS Further, by this oxidation of the polyhydric alcohols we obtain not only aldehydes, ketones, and acids, but also numerous compounds which possess a double chemical char- acter in so far as they unite in themselves the properties of more than one of these classes of compounds. These are the hydroxy aldehydes, which are at the same time aldehyde and alcohol, the hydroxy ketones, at the same time ketone and alcohol, the hydroxy acids, aldehyde acids, ketone acids, and ketone aldehydes. An aldehyde acid, for instance, is capable, as an acid, of forming salts, esters, and amides on the one hand; and on the other, as an aldehyde, it is able to reduce an ammoniacal silver solution, to combine with NaHS0 3 , and to react with hydroxylamine, &c. SUMMARY OF THE OXIDATION PRODUCTS (a) Of the di-primary alcohols. CHO CH 2 -OH CH 2 -OH Glycol CH 2 -OH "^CHO Glycollic aldehyde CHO Glyoxal CH 2 -OH CO-OH Glycollic acid ^ CHO * CO-OH^ Glyoxalic acid. CO- OH CO-OH Oxalic acid Possible products: Di-aldehydes, dibasic acids, hydroxy aldehydes, hydroxy acids, aldehyde acids. (b) Of the hydroxy primary-secondary alcohols. CH, Methyl-glyoxal CH 2 -OH -Propylene glycol CH-OH - CHO (Lactic aldehyde, unknown) CH 3 CH-OH CO- OH Lactic acid CO- OH .=0 If I! MONOHYDROXY FATTY ACIDS 205 Possible products: hydroxy aldehydes, hydroxy ketones, ketone aldehydes, hydroxy acids, ketone acids. (c) Of the di-secondary alcohols: hydroxy ketones, di- ketones. (No dibasic acids or alcohol acids, C n .) e.g. : CHg-CH-OH CH 3 .CH.OH CH 3 .CO CH 3 .CH.OH " " CH 3 .CO ' CH 3 .CO Di-secoudary butylene glycol Dimethyl-ketol Di-acetyl. (d) The tri- and polyhydric alcohols are capable of yielding the most various products upon oxidation, especially poly- hydroxy ketones, polyhydroxy acids, keto-acids, and polybasic acids. Of all these oxidation products, the most important are the hydroxy acids, the polybasic acids, and the keto-acids. For the sake of convenience the hydroxy monobasic acids will be treated of first. IX. HYDROXY MONOBASIC ACIDS AND COM- POUNDS RELATED TO THEM A. Monohydroxy Fatty Acids These compounds may be regarded as monohydroxy deri- vatives of the fatty acids, e.g. OH-CHg-COnH, hydroxy acetic acid, or glycollic acid, OH CH 2 CH 2 C0 2 H, ^-hydroxy pro- pionic acid, or /2-lactic acid, &c. They combine within themselves the properties of a mono- basic acid and of an alcohol, and are consequently capable of forming derivatives as alcohols, as acids, and as both together. The lowest members of the series, which are the most im- portant, are glycollic acid and lactic acid, both syrupy liquids which solidify to crystalline masses in the desiccator, and readily give up water to form anhydrides. They cannot be volatilized without decomposition; and are readily soluble in water, and for the most part also in alcohol and ether. Formation. 1. By the regulated oxidation of the glycols. (See Summary, p. 204.) 2. From the fatty acids, through their monohaloid substi- tution products, the halogen of these being easily replaced by 206 IX. HTDROXY MONOBASIC ACIDS hydroxyl, either by means of moist oxide of silver or often by prolonged boiling with water alone: CH 2 C1.C0 2 H + H 2 = CH,(OH).C0 2 H This reaction is conditioned by the halogen having the a-position with respect to the carboxyl (cf. pp. 169 and 170). For a reaction of these haloid-substitution products in a different direction, see fi- and y-hydroxy acids. 3. From the aldehydes and ketones containing 1 atom of carbon less, by the preparation of their hydrocyanic acid com- pounds, cyanhydrins (see pp. 126 and 135), and hydrolysis of the latter. Thus, irom aldehyde is produced ethylidene cyanhydrin, and from this a-lactic acid: CH 3 .CH(OHXCN) + 2H 2 = CH 3 .CH(OH).CO 2 H + NH 3 . Since the aldehydes and ketones are easily obtained from the corresponding alcohols, this reaction furnishes a means of preparing the acids, C n H 2n (OH) (C0 3 H), from the alcohols, C n H 3n+l (OH), i.e. of introducing carboxyl into the latter in place of hydrogen; this is a most important synthesis. 4. From the glycollic cyanhydrins by saponification, e.g. /2-lactic acid from ethylene cyanhydrin: OH.CH 2 .CH 2 .CN + 2H 2 = OH-CH^CHa-CO.^ -f NH 3 . As the cyanhydrins can be readily obtained from the glycols (p. 191), this formation of hydroxy acids represents an exchange of a hydroxyl of the glycol for carboxyl, and is analogous to the formation of acetic acid from methyl alcohol. Thus : OH.CH 2 .CH 2 -OH OH-CH 2 .CHoCl OH.CH 2 -CH 2 .CN OH.CH 2 .CH 2 .C0 2 H and CHj-OH CH 3 C1 CH 3 .CN CH 3 .CO 2 H. 5. By the reduction of aldehyde acids or ketonic acids, e.g. lactic from pyruvic acid (p. 225). This reaction corresponds with the formation of the alcohols from the aldehydes or ketones by reduction. 6. By the action of nitrous acid upon amino acids (see Gly- cocoll); a reaction analogous to the formation of alcohols from amines (p. 108). 7. Hydroxy acids of the fatty series containing an equa] number of carbon atoms result by direct oxidation, if a CH NOMENCLATURE OF HYDROXY ACIDS 207 group, i.e. a "tertiary" hydrogen atom, is present in the original acid (E. Meyer, B. 11, 1283; 12, 2238): (CH 3 ) 2 CH.C0 2 H laobutyric acid a-Hydroxy-isobutyric acid. Constitution and Isomers. As hydroxy compounds of the fatty acids, the acids of the foregoing series can exist in as many modifications as the monohaloid fatty acids. Thus there is only one glycollic acid, corresponding with monochloracetic acid, but two lactic acids corresponding with a- and /2-chloro- propionic acids are possible, and both actually exist; they are designated as a- and /3-hydroxy propionic acids: O^ (a-chloro-propionic acid). CH 3 CH(OH)-CO^[ (a-hydroxy -propionic acid or common lactic acid). CH 2 ICH 2 -CO 2 H (/3-iodo-propionic acid). OH-CH 2 -CH 2 -CO 2 H (jS-hydroxy propionic acid or /3-lactic acid) From the two butyric acids can be theoretically derived: (a) From the normal acid: CH 3 .CH 2 .CH 2 .CO 2 H, y ft an a-, ft-, and y-hydroxy butyric acid. (b) From isobutyric acid : an a- and /3-hydroxy isobutyric acid. Systematic Nomenclature. OH . CH 2 CH 2 C0 2 H, Propane-3- jlrl-acid; (CH 3 ) 2 C(OH) C0 2 H, 2 -Methyl-propane- 2 -ol-l-add] OH.CH 2 .CH 2 .CH 2 .C0 2 H, Butane4-ol-\-add, &c. The constitution of these hydroxy acids can often be deduced from their methods of formation. Thus the preparation of common lactic acid from aldehyde, CH 3 -CHO, according to method 3, shows that it contains the group CH 3 -CH:, "ethy- lidene"; it is therefore termed "ethylidene lactic acid" On the other hand, the formation of /3-hydroxy propionic acid from glycol cyanhydrin, according to 4, is a proof of its con- taining the group .CH 2 .CH 2 ., "ethylene"; hence the name "ethylene lactic acid". The constitution can also frequently be deduced from a study of their oxidation products; if they can be oxidized, for instance, to dibasic acids (which contain two carboxyls), 208 IX. HYDROXY MONOBASIC ACIDS then they must contain a primary alcohol group, CH 2 OH, since only such a group yields a new carboxyl on oxidation. Ethylene lactic acid is therefore a "primary" alcohol acid. Its isomer, ethylidene lactic acid, is similarly a "secondary" alcohol acid, while a-hydroxy isobutyric acid is a " tertiary alcohol acid, i.e. acid and tertiary alcohol at the same time. Behaviour. 1. The double chemical character of the hydroxy acids will be dealt with more in detail under Glycollic Acid. As acids they form salts, esters, and amides; as alcohols they yield ethers, amines, &c. Of these derivatives the alcoholic amines of the acids, the so-called amino acids, are of especial interest. (See Glycocoll, p. 211.) 2. The hydroxy acids form different kinds of anhydrides, viz.: (a) as alcohols (see Di-glycollic Acid); (b) one molecule as alcohol forms with a second molecule as acid an ester, with elimination of H 2 (see Glycollic Anhydride); (c) operation b is repeated, the first molecule acting as acid, and the second as alcohol (see Glycolide); (d) one molecule loses H 2 0, with formation of an " intramolecular " anhydride, a so-called ladone (see p. 217). 3. For behaviour upon oxidation see p. 207, and also the individual compounds. 4. Just as the alcohols readily give up water, yielding olefines, so many of the hydroxy acids, especially the ft-, can be transferred into unsaturated monobasic acids. (See Hydra cry lie Acid, p. 216.) 5. When warmed with hydriodic acid, the hydroxy acids are reduced to the corresponding fatty acids, just as the alcohols are converted by this reagent into hydrocarbons. 6. When the a-hydroxy acids are warmed with dilute sul- phuric acid, formic acid is produced together with the alde- hyde or ketone which would give rise to the acid, according to method 3. The /2-hydroxy acids, on the other hand, decom- pose into water and acids of the acrylic series. Thus : CH 3 .CH:0-f H- OH.CH 2 .CH 2 .CO 2 H = CH 2 :CH.CO 2 H + The a-, /?-, -y-, &c., hydroxy acids also differ from each other in the facility with which they form anhydrides. (See Lactones, p. 217.) GLYCOLLIC ACID 209 Glycollic Acid, Hydroxy-acetic acid, Ethanolic add, OH-CH 2 . C0 2 H (Strecker, 1848), occurs in unripe grapes, in the leaves of the wild vine, &c. Formation. 1. By the oxidation of glycol with dilute HN0 3 ( Wurtz). 2. Together with glyoxal and glyoxylic acid, by the oxida tion of alcohol with dilute HN0 3 . 3. By the reduction of oxalic acid with Zn + H 2 S0 4 . 4. From formic aldehyde synthetically, according to method 3, y. 206. 5. It is usually prepared by boiling chloro-acetic acid with water in the presence of marble, the marble serving to neutralize the HC1 formed in the reaction (A. 200, 76): CH 2 C1.C0 2 H + H 2 ^ OH.CH 2 .C0 2 H + HC1. Properties. It forms colourless needles or plates, is readily soluble in water, alcohol, and ether, and melts at 80. Nitric acid oxidizes it to oxalic acid. The alkaline salts are hygro- scopic, the calcium salt and the magnificent blue copper salt are sparingly soluble in water. K = 0*0152. Derivatives. (See table, p. 210.) As an acid, gly collie acid forms salts, esters e.g. ethyl glycollate a chloride, glycollyl chloride, and glycollamide, all of which are readily hydro- lysed, some of them even on warming with water. All those derivatives still retain their alcoholic character. If, on the other hand, glycollic acid forms derivatives as an alcohol, the properties of the alcoholic derivatives in question are combined with those of an acid, since the hydroxyl of the alcoholic group, -CHg-OH, enters into reaction, while the carboxyl group remains unchanged. These derivatives are either ethers, such as ethyl-glycollic acid (see table), or e.g. amines, such as glycocoll, and, as alcoholic derivatives, they are not readily hydrolysed; or they are esters ^f glycollic acid, as alcohol, e.g. acetyl-glycollic acid, CH 2 (0 . CO CH 3 ) . C0 2 H, or monocMoracetic acid, CH 2 C1-C0 2 H (the hydrochloric ester of glycollic acid), and then they are of course saponifiable. These latter compounds still retain their acid character, and therefore form, on their part, esters, chlorides, and amides, which are also readily hydrolysed. The following table gives a summary of the more important derivatives of glycollic acid : (B480) 210 IX. HYDROXY MONOBASIC ACIDS Acid Derivatives Alcoholic Derivatives. Mixed Derivatives. HO.CH 2 .CO-ONa Sodium glycollate. NaO.CH 2 .CO-ONa Di-sodium glycollate. Hygroscopic; decomp. by H^.0 into Na salt and NaOH. HO.CH 2 .CO-OC 2 H 5 Ethyl glycollate. Liquid, b.-pt. 160. OCiHs-CHa-CO-OH Ethyl-glycollio acid. Liquid, b.-pt. 206. C 2 H S .O.CH 2 .CO.OC 2 H 5 Ethylic ethyl-glycollate. Liquid, b.-pt. 152. HO-CH 2 .CO.C1 Glycollyl chloride. Oil ; decomposes on volatilizing. CH 2 C1.CO.OH Moiiochloracetic acid. CH 2 C1-COC1 Mon ochloracety 1 chloride. Liquid, b.-pt. 120, of suffocating odour. HO.CH 2 .CO.NH S Glycollamide. Crys. M.-pt. 120; does not form salts with bases. NH 2 .CH 2 .CO-OH Glycocoll. Crys. M.-pt. 236. Forms salts with acids and bases. NH 2 .CH 2 .CO.NH 2 Glycocollamide. Crys. It is easy to see that the corresponding derivatives of the first and second vertical rows are always isomeric. Anhydrides of Glycollic Acid. 1. Glycollic acid can yield different types of anhydrides: (1) the elimination of one mol. of water from the alcoholic hydroxyls of two molecules of the acid produces diglycollic acid, 2 -CO 2 H 2 -C0 2 H, which is obtained by boiling monochloracetic acid with lime. It forms large rhombic prisms, is a dibasic acid, and, as an ether, is not saponified when boiled with alkalis, but is decom- posed when heated with concentrated hydrochloric acid to 120. 2. Diglycollic acid loses water when heated, yielding the diglycollic anhydride, 3. Glycollic anhydride, OH.CH 2 .CO.O.CH 2 .CO 2 H, is an ester, which is formed when glycollic acid is heated at 100. It becomes hydrated again when boiled with water, and may be regarded as an ester derived from glycollic acid acting as an alcohol and as an acid. GLYCOCOLL 211 CH 2 .O.CO 4. Glycohde, - . , is also an ester anhydride, and OU U Oiig is isomeric with 2 (and with fumaric acid). It is formed when sodium bromo-acetate is distilled in a vacuum. Lustrous plates; m.-pt. 87. It becomes hydrated again when boiled with water. Glycocoll (Ammo -ethane acid), glycine, amino- acetic add., NH 2 .CH 2 .C0 2 H (Braconnot, 1820). This is the simplest representative of the important class of amino acids, so called because they are derived from the fatty acids by the exchange of a hydrogen atom of the hydrocarbon radical for an amino group, e.g. CH 3 .C0 2 H, acetic acid; CH 2 (NH 2 ) C0 2 H, amino- acetic acid. Formation. 1. By the action of concentrated ammonia upon monochloracetic acid (Heintz, A. 122, 261; Kraut, A. 266, 292): CH 2 C1.C0 2 H (cf. also B. 23, Eef. 654). Di- and triglycollamic acids, NH(CH 2 .C0 2 H) 2 and N(CH 2 . C0 2 H) 3 , are produced at the same time. a-Chloropropionic acid in like manner yields alanine with ammonia (see Lactic Acid). The method is a general one for the production of amino acids. 2. By boiling glue with alkalis or acids. 3. Together with benzoic acid, by decomposing hippuric acid, i.e. benzoyl-glycocoll, with concentrated hydrochloric acid: Properties. Glycocoll forms large colourless rhombic prisms, readily soluble in water, but insoluble in absolute alcohol and ether. It has a sweet taste, hence the name " glue sugar " or glycocoll (yXvKvs, sweet, KoAXa, glue). It melts and decom- poses at 236. Glycocoll, like all the amino acids, possesses the properties of both an amine and an acid. It therefore forms salts with acids as well as with bases, e.g. glycocoll hydrochloride, C 2 H 5 N0 2 HC1, which crystallizes in prisms, and the characteristic copper salt, copper glycocoll, (C 2 H 4 N0 2 ) 2 Cu + H 2 > which crystallizes in blue needles, the latter being obtained by dissolving cupric oxide in a solution of glycocoll. Most of the other amino acids also form characteristic copper salts of this nature, which serve for their separation. Glycocoll 212 IX. HYDROXY MONOBASIC ACIDS also yields compounds with salts, and, as an acid, forms an ethyl ester, an amide, &c. (see table, p. 210). When heated with BaO it is decomposed into methyl-amine and C0 2 , while nitrous acid converts it into glycollic acid (the normal reaction of the primary amines). With ferric chloride it produces an intense red, and with copper salts a deep-blue coloration. Ethyl armno-acetate (b.-pt. 43/ll mm.) and nitrous acid N \ yield the interesting ethyl diazo-acetate, || yCH'CO'OC 2 H 5 , from which hydrazine, NH 2 NH 2 , and its hydrate were first prepared; and from the latter the remarkable compound, hydrazoic acid, N 3 H (Curtius, J. pr. Ch. (2) 38, 396, 472; 43, 207; B. 24, 3341; 29, 759; 33, 58). See also Di and Triazo Derivatives, Chap. LI. Constitution (see B. 16; 2650). Free glycocoll may possibly be an intramolecular salt, corresponding with the formula CH 2 <Q^ 3 > (see Taurine, p. 197, and Betaine below). Alkyl and Acyl Derivatives of Glycocoll: Methyl-glycocoll Trimethyl-glycocoll Acetyl-glycocoll or Sarcosine, or Betaine, or Aceturic Acid, CH 2 .NHCH 3 CH 2 .N(CH 3 00- OH CO-0 - ' CO-OH. Most of these alkyl derivatives are interesting, as they either occur as such in natural products, or may be obtained by the decomposition of certain natural compounds. Sar- cosine is obtained by the decomposition of the complex natural substances creatine or caffeine. Betaine occurs in beet-root, and is present in large quantities in the molasses from beet-root sugar. It crystallizes with 1 H 2 0, which it . readily gives up on heating. This hydrate may possibly be C0 2 H CH 2 NMe 3 OH. When heated at 293 betaine is transformed into the isomeric methyl ester of dimethylamino- acetic acid, NMe 2 -CH 2 .COOMe; at higher temperatures it yields trimethylamine. It has been synthesised by the action of trimethylamine on monochloracetic acid (B. 1902, 35, 603): d-CHj-COOH -> (CH 3 ) 3 N(C1).CH 2 .CO.OH (CH 3 ) 3 N.CH 2 .CO. Numerous other compounds of a similar type are known, and are all usually termed betaines. LACTIC ACIDS 213 Lactic Acids (Hydroxy-propionic acids). (Wislicenus, A. 128, 1; 166, 3; 167, 302, 346.) As has been already mentioned, two isomeric lactic acids are theoretically possible, viz. a- and /3-hydroxy-propionic acids, a- and /?-lactic acids, or ethylidene- and ethylene-lactic acids, and both of these are known. The minute investigation of the different lactic acids has been of very great importance for the development of chemical theory; they were formerly held to be dibasic, and the recog- nition of their hydroxy-monobasic nature has materially con- tributed to the acceptation of the theory of the linking of atoms. The molecule of a-hydroxy-propionic acid contains an asymmetric carbon atom, CHo-CH II and hence should exhibit exactly the same kind of isomerism as was met with in the case of active valeric acid. In reality two optically active a-lactic acids are known, one of which is dextro (d\ and the other laevo (I) rotatory. These two acids are identical in all their properties, with the excep- tion of optical activity. A mixture (or compound) of the two in equal quantities is optically inactive, and is known as inactive (dl) or racemic (r) lactic acid. The molecule of /?-hydroxy-propionic acid does not contain an asymmetric carbon atom, and hence exists in only one modification, which is optically inactive. i Modes of Formation. Fermentation Lactic Acid. Ethylene-lactic Acid. i 1. By the regulated! oxidation of / a-Propylene glycol, CH 3 .CH(OH).CH 2 OH. jS-Propylene glycol, OH.CH 2 .CH 2 .CH 2 OH 2. By the exchange"! of halogen for >- a-Chloro-propionic acid, S-Iodo-propionic acid, CH 2 I.CH 2 .CO.OH. hydroxyl in J CH 3 .CHC1.CO-OH. 3. By hydrolysis of-! Aldehyde-cyanhydrin, CH 3 .CH(OH)-CN. E t hy lene-cy anhy drin , OH.CH 2 .CH 2 -CN. 4. B}f action of ni-\ Alanine, irons acid upon/ CH 3 .CH(NH 2 ).CO.OH. 5. By the reduction! Pyro-racemic acid, of CHs-CO-CO-OH. 6. By the lactic fermentation of sugar, etc. 214 IX. HYDROXY MONOBASIC ACIDS 1. dl-Ethylidene- lactic Acid (Propane-2-ol-l-acid), ordinary fermentation lactic acid, CH 3 CH (OH) C0 2 H. Discovered by Scheele, and recognized as hydroxy-propionic acid by Kolbe. Occurs in opium, sauerkraut, and in the gastric juice. Preparation. This depends upon the so-called lactic fer- mentation of sugars, e.g. milk, cane- and grape-sugars, and of substances related to them, such as gum and starch; it is induced by certain species of bacteria commonly spoken of as the lactic bacilli. The fermentation proceeds best at a tempera- ture of 34-35 in a nearly neutral solution, this last condition being attained by the addition of chalk or zinc-white to the fermenting mixture. The free acid can then be liberated from the lactate of zinc by sulphuretted hydrogen. When a non-homogeneous ferment (e.g. decaying cheese) is used, the lactic acid at first produced is readily transformed by other organisms into butyric acid (p. 152). Lactic acid is also produced in large quantity by heating grape- or cane-sugar with caustic-potash solution of a certain degree of concentration (B. 15, 136). The relations of lactic acid to the sugar varieties appear, at a superficial glance, to be very simple; thus grape-sugar, C 6 H 12 6 , and lactic acid, C 3 H 6 3 , are polymers. Lastly, the inactive acid is produced by mixing equal quan- tities of the two active modifications. In syntheses the latter are formed in equal amounts, and hence the inactive acid is obtained. Properties. When its solution is evaporated in a desiccator, a thick, non-crystallizing and hygroscopic syrup is obtained, which is miscible with water, alcohol, and ether, and which gradually loses water, yielding the solid lactic anhydride, C 6 H 10 5 , before all the water of solution has been got rid of. To obtain the pure acid it is necessary to distil under very low pressures, when a crystalline solid melting at 18 is obtained. K = O0138. When heated, it is partially con- verted into the anhydride, lactide, C 6 H 8 4 , and partially into aldehyde, CO, and H 2 0. Similarly it decomposes into alde- hyde and formic acid when heated with dilute sulphuric acid to 130, concentrated sulphuric giving rise to carbon monoxide instead of formic acid : CH 3 .CH(OH).CO 2 H = CH 3 .CHO + HCO 2 H. When oxidized, it yields acetic and carbonic acids; hydro- bromic acid converts it into a-bromo-propionic acid, and boiling hydriodic acid into propionic acid itself. LACTIC ACIDS 2l5 The inactive acid is split up into the two active modifications by the crystallization of the strychnine salts (Purdie and Walker, J. C. S. 1892, 754); further, when green mould, Peni- cillium glaucum, is sown in a solution of the ammonium salt of the inactive acid, the Isevo-acid is assimilated more rapidly than the dextro-, and the solution thus becomes optically active (Linossier, B. 1891, 24, 660). A very simple resolution has been accomplished by Purdie (J. C. S. 1893, 1143) by crys- tallizing the zinc ammonium salt, ZnC 6 H 10 6 , NH 4 C 3 H 5 3 , 2H 2 0. (Cf. Eesolution of Racemic Acid.) A number of well-defined salts are known, e.g. Calcium lactate, (C 3 H 5 3 ) 2 Ca + 5H 2 0; zinc lactate, (C 3 H 5 3 ) 2 Zn + 3H 2 0; ferrous lactate, (C 3 H 5 3 ) 2 Fe + 3H 2 0. When sodium lactate is heated with sodium, di- sodium lactate, CH 3 CH(ONa) C0 2 Na, which is at the same time a salt and an alcoholate, is formed. The derivatives of lactic acid are derivatives of it either as acid or as alcohol, and are perfectly analogous to those of glycollic acid (see table, p. 210). Thus ethyl-lactic acid, a-ethoxy-propionic acid, CH 3 CH(OC 2 H 5 ) C0 2 H, a thick acid liquid which boils almost without decomposition, corresponds with ethyl-glycollic acid; ethyl lactate, which can be distilled without decomposition, with ethyl glycollate; lactamide, CH 3 .CH(OH).CO.NH 9 , with glycollamide; and alanine, CH 3 .CH(NH 2 ).CO.OS, with glycocoll. By the action of PC1 5 , lactyl chloride, CHg-CHCl-CO-Cl (p. 171), is formed; as the chloride of a-chloro-propionic acid it is decomposed by water, yielding the latter acid and HC1. The following anhydrides of lactic acid are known : (1) Lactylic acid or Lactic anhydride, C 6 H 10 5 , which is analogous to glycollic anhydride, and forms a yellow amor- phous mass. (2) Lactide, C 6 H 8 4 , analogous to glycolide (plates melting at 125). (3) Dilactic acid, C 6 H 10 5 , the alcoholic anhydride, analogous to diglycollic acid. 2. d-Ethylidene-lactic acid, Sarco-ladic add, para-lactic acid (Liebig). This occurs in the juice of flesh, and is therefore to be found in Liebig's extract of meat. It results from certain fermentations. Its chemical properties are exactly similar to those of ordinary lactic acid; thus it readily yields lactide or aldehyde. Its salts differ to some extent, however, from those of the latter; thus, the zinc salt, + 2H 2 0, is much more easily soluble, and the calcium salt + 4H 2 0, much more sparingly soluble than the corresponding common lactates. Such differ- 216 ix. HYDROXY MONOBASIC ACIDS ences are usually met with between d- and ^-compounds on the one hand, and their r-isomeride on the other. 3. 1-Ethylidene-lactic acid is obtained from the fermenta- tion of cane-sugar by means of the l-ladic bacillus. Its salts correspond exactly with the salts of d-lactic acid. They have the same formulae, same solubilities, &c. 4. Ethylene-lactie acid (Propane-3-ol-l-acid), hydracrylic acid (Wislicmus, A. 128, 1), forms a syrupy mass. It differs from lactic acid (a) by its behaviour upon oxidation, yielding car- bonic and oxalic acids, and not acetic; (b) by not yielding an anhydride when heated, but by breaking up into water and acrylic acid, hence the name hydracrylic acid: CH 2 (OH).CH 2 .COOH = CH 2 :CH.COOH + H 2 0; (c) in solubility, and in the amount of water of crystallization of its salts (e.g. zinc salt, + 4H 2 0, very readily soluble in water; calcium salt, + 2 H 2 0). It is not so strong an acid as a-lactic acid. K = 0-00311. It may be synthesised from ethylene by means of the fol- lowing series of reactions: (a) the addition of hypochlorous acid, (b) conversion of the chlorhydrin into the corresponding nitrile, and (c) hydrolysis, e.g. : CH 2 :CH 2 * OH.CH 2 .CH 2 C1 -* OH.CH 2 .CH 2 .CN -^ OH.CH 2 .CH 2 .C0 2 H. Hydroxy-caproic Acids, Leucine or a-Amino-caproic acid, CH 3 .CH 2 .CH 2 .CH 2 .CH(NH 2 ).C0 2 H, is a derivative of a-hy- droxy-caproic. It forms glistening plates, and, like other amino acids, is closely related to albumen. It is found in old cheese, also abundantly in the animal organism in the gastric gland, and in the shoots of the vetch and gourd, &c. It forms, along with tyrosine, a constant product of the digestion of al- bumen in the small intestine and of the decay of albuminous substances, and is formed when the latter are boiled with alkalis or acids. It has also been prepared synthetically. It closely resembles glycocoll, and forms a characteristic sparingly soluble blue copper salt. Leucine is dextro-rotatory. A laevo- and an inactive modification are also known (B. 24, 669). LeSueur (J. C. S. 1904, 827; 1905, 1888) has prepared several hydroxy derivatives of the higher fatty acids, e.g. a-hydroxy- margaric and a-hydroxy-stearic acids, and has found that a good yield (35-60 per cent) of an aldehyde can be obtained when the acid is heated to 240-250. The molecule of the LACTONES 217 aldehyde so obtained contains a carbon atom less than the molecule of the hydroxy acid, and water, formic acid, carbon monoxide, and a lactide are obtained as by-products. LACTONES All hydroxy acids tend to lose water under certain con- ditions, yielding anhydro-compounds. The manner in which this water is eliminated is very different in the various types of hydroxy acids. 1. In the case of the a-hydroxy acids, 1 or 2 mols. of water are usually eliminated from 2 molecules of the acid, yielding compounds of the type of diglycollic acid, glycollic anhydride, &c. 2. In /2-hydroxy acids 1 molecule of water is usually elimi- nated from 1 molecule of the acid, and an a-/3-unsaturated acid is formed, e.g. : CH 3 .CH(OH).CH 2 .C0 2 H -> CH 3 .CH:CH.C0 2 H (crotonic acid). 3. In the case of y-hydroxy acids, e.g. y-hydroxy-butyric acid, OH.CH 2 .CH 2 .CH 2 l .C0 2 H, 1 molecule of water is elimi- nated from 1 molecule of the acid, and an inner anhydride or lactone is formed, 2 2 = butyro-lactone or butanolid. CH 2 CO / The formation of such a lactone is characteristic of y-hydroxy acids. Many of these acids are so unstable in the free state, that when mineral acid is added to their salts the lactones and not the free acids are obtained. The "y-lactones" are for the most part neutral liquids of faint aromatic odour, readily soluble in alcohol and ether, and distilling without decomposition. They dissolve in alkalis, yielding the salts of the corresponding hydroxy acids, and form brominated fatty acids with HBr, and amino acids or amides of y-hydroxy acids with NH 3 (B. 23, Ref. 234). 8- and /?-, but only a few a-lac tones, from 8-, /?-, and a-hy- droxy acids, are also known. They show marked differences in the ease with which they are formed and in their stability, the y-lactones being the most stable. (For a-Lactones, see B. 1891, 24, 4070; for ft-, B. 1897, 30, 1954.) The formation of lactones by warming the isomeric unsatu- rated acids, CJI^f)^ which contain the double bond in the 218 IX. HYDHOXY MONOBASIC ACIDS /?-y or 7-8 position, with HBr or with moderately concentrated H 2 S0 4 , is worthy of note, e.g. : E.CH:CH.CH 2 .CO 2 H -* K.CH.CH 2 .CH 2 .Cp. (For details, see Fittig and his pupils, A. 208, 37, 111; 216, 26; 255, 1, 275; 256, 50; 268, 110.) The reaction is generally regarded as the addition of HBr or H 2 O to the double bond, and then the elimination of the Br or OH in the y-position with the H of the carboxyl group. B. Polyhydrie Monobasic Acids Just as glycol on oxidation can yield the monohydroxy monobasic acid, glycollic acid, so the polyhydric alcohols on careful oxidation with nitric acid can yield polyhydroxy monobasic acids, e.g.: OH.CH 2 .CH(OH).CH 2 .OH OH.CH 2 .CH(OH).C0 2 H. They are usually designated according to the number of alcoholic hydroxyl groups present. This number can be determined by converting the acid, or better, its ester, into the acetyl derivative, and estimating the number of acetyl groups by analysis or by hydrolysis (p. 201). In none of these acids do we find more than one OH group attached to the same carbon atom. All have the properties of monobasic acids and, in addition, the properties of polyhydric alcohols. Those which contain a hydroxyl group in the y-position yield lactones. Most of the compounds belonging to this class either crys- tallize badly or are gum-like. A number of these acids are formed by the cautious oxidation of the sugars or of the unsaturated acids, CJi^.flz (see p. 162). I. DIHYDROXY MONOBASIC ACIDS Glyceric acid (Propane-2:3-diol-l-acid), OH.CH 2 -CH(OH). C0 2 H, is a syrupy liquid which is obtained by the cautious oxidation of glycerol. The molecule contains an asymmetric carbon atom, the artificial acid is optically inactive, but a d- and an /-modification are known (Frankland, J. 0. S. 1891, 96). Various compounds obtained from natural sources are closely related to the dihydroxy acids, viz. serine, a-amino-^-hydroxy POLYHYDRIC MONOBASIC ACIDS 219 propionic acid, obtained by boiling silk glue with dilute acids; ornithine, aS-diamino- valeric acid; and lysine, ae-diamino- caproic acid, obtained by the hydrolysis of casein. II. TETBA- AND PENTAHYDROXY MONOBASIC ACIDS The tetra- and pentahydroxy acids, e.g. OH CH 2 (CH OH), C0 2 H and OH.CH 2 .(CH.OH) 4 .C0 2 H, are of particular im- portance, on account of their close connection with the simple sugars. They are obtained either by the cautious oxidation of the corresponding sugars, e.g. by means of bromine water : or by the reduction of the corresponding dibasic acids (sac- charic acid, &c.); or, lastly, by the addition of hydrocyanic acid to the polyhydroxy aldehydes or ketones, just as lactic acid is formed from aldehyde. Conversely, the acids, in the form of their lactones, are on the one hand reconverted into the sugars by reduction with sodium amalgam; while, on the other hand, they are oxidized by nitric acid to the correspond- ing dibasic acids. The acids are named according to the sugar to which they are related: Arabinose -> Arabonic Acid, Glucose * Gluconic Acid. (See Sugars, p. 300, &c.) Some of the acids are known in the form of their lactones only. The phenyl-hydrazones are frequently made use of for their isolation. A number of different acids, e.g. mannonic, gluconic, gulonic, galactonic, and talonic acid, have been obtained by the oxida- tion of the hexoses (p. 307) and by other methods. Inves- tigation has shown that those acids all possess the same structural formula, OH CH 2 . CH(OH) CH(OH) . CH(OH) CH(OH) CO 2 H, which is seen to contain 4 distinct asymmetric carbon atoms. The acids are thus stereo-isomeric ; their differences depend on the arrangement in space of the different radicals (cf. the Sugars). The number of stereo-isomerides possible is the same as for the sugars (the corresponding aldo-hexoses), viz. eight pairs of optically active isomerides and eight racemic compounds. Most, but not all, of these have been obtained. Three extremely important methods have been employed (mainly by E. Fischer) for the preparation of these acids: 220 IX. HYDROXY MONOBASIC ACIDS 1. Oxidation of the corresponding aldehyde (a sugar), e.g. ordinary glucose when carefully oxidized with chlorine- or bromine- water yields d-gluconic acid: OH.CH 2 .(CH-OH) 4 .CH:O -> OH.CH 2 .(CH.OH) 4 .CO-OH. 2. From a stereo-isomeric acid by intramolecular transfor- mation under the influence of high temperature, and generally in the presence of an organic base, e.g. d-gluconic heated with quinoline and water yields d-mannonic; galactonic * talonic. The reaction is a reversible one, and hence the final product is a mixture of the two acids, which can be separated by the difference in solubility of certain of their salts. 3. The addition of hydrogen cyanide to a polyhydric alde- hyde or ketone and subsequent hydrolysis, e.g. : -OHVCHO OH-CH 2 .(CH.OH) 3 .CH(OH).CN OH.CH 2 .(CH.OH) 3 .CH(OH).C0 2 H. It is obvious that an additional asymmetric carbon atom is introduced by the addition of the HCN, and thus a mixture of two stereo-isomeric nitriles is formed, and on hydrolysis a mixture of two stereo-isomeric acids, e.g. : 7 A ,1 . _ __ -Z-Glucomc acid -^-Mannonic acid. This reaction is somewhat similar to the addition of HCN to acetaldehyde, the main difference is that the original com- pound is optically active, and hence its molecule is asymmetric. By the addition of HCN two compounds are obtained, as a rule not in equal amounts, both of which are optically active, but do not stand in the relationship of object to mirror image. This reaction has been extended, and hydroxy acids con- taining 7, 8, and 9 carbon atoms have thus been obtained. C. Hydroxy Aldehydes As examples, we have glycollic aldehyde, OH CH 2 CH : 0, aldol, CH 3 .CH(OH).CH2-CH:0 (see p. 131), and glyceric aldehyde, OH.CH 2 .CH(OH).CH:O. The last-named is con- tained in glycerose, a product obtained by oxidizing glycerol with bromine water. Alkalis convert it into a mixture of sugars, C 6 H 12 6 (see a-Acrose). (For further examples of hy- droxy aldehydes and ketones, see Sugars, p. 300.) DIKETONES 221 D. Dialdehydes (cf. p. 97) Glyoxal (Ethane-dial), CHO-CHO (Debus, 1856), is formed by the careful oxidation of alcohol, or better, of aldehyde; it possesses all the characteristic properties of aldehydes; one molecule of the aldehyde is capable of combining with two of hydrogen cyanide or of sodium hydrogen sulphite. E. Diketones 1. Diacetyl, Butane-dione, a-diketo-butane, CH 3 COGOCH 3 , b.-pt. 87-88. This can be prepared by boiling iso-nitroso- methyl acetone, CH 3 - C( : N OH) CO CH 3 , a product obtained by the action of nitrous acid on methyl ethyl ketone, with dilute H 2 S0 4 , when the oximino group is replaced by oxygen. It is a yellow-green liquid, its vapour having the colour of chlorine, and an odour similar to that of quinone (v. Pechmann, B. 20, 3162; 24, 3594; Fittig and his pupils, A. 249, 182). Reduction converts it into dimethyl-ketol. Homologues are known (cf. B. 22, 2115). 2. Acetyl-acetone, CH 3 .CO.CH 2 .CO-CH 3 , is formed by the action of aluminic chloride upon acetyl chloride and sub- sequent decomposition of the aluminium compound, or better (B. 22, 1009), by the action of sodium upon a mixture of ethyl acetate and acetone (see Aceto-acetic ester synthesis, p. 224): CH 3 .CO-OC 2 H 6 + CHo-CO It is a liquid which boils at 137. 3. Acetonyl- acetone, y-diketo-hexane, CH 3 COCH 2 CH 2 ' CO-CH 3 , may be prepared from monochlor-acetone and ethyl aceto-acetate (B. 17, 2756); also from diaceto-succinic ester (B. 22, 168, 2100). It is a liquid of pleasant odour, and boils at 188. These three compounds are the simplest representatives of the a-, ft-, and y-diketones, or of the 1:2-, 1:3-, and l:4-di- ketones, i.e. of those diketones whose carbonyl groups are either next to one another (a-position), or separated by ona carbon atom (^-position), or separated by two (y-position). As diketones they yield mono- and dioximes, and also mono- and dihydrazones. Such dihydrazones, and also those 222 IX. HYDROXY MONOBASIC ACIDS from the dialdehydes, are termed osazones, e.g. diacetyl osazone. C 6 H 6 .NH.N:CMe.CMe:N.NH.C 6 H 6 . Osazones are also formed by the action of phenylhydrazino on polyhydroxy aldehydes or ketones, e.g. glucose and fructose, an atom of oxygen being at the same time taken up; they are mostly yellow in colour (cf. the phenyl-hydrazine compounds of the carbohydrates). The diketones show the most varied behaviour on condensa- tion. By the action of alkali on the a-diketones, they yield benzene derivatives (see Quinone); the /3-diketones readily pass into pyrazole and isoxy-azole derivatives, and serve for the synthesis of derivatives of quinoline; while the y-diketones are easily converted into derivatives of pyrrole, furane, and thiophene, and the S-diketones into derivatives of pyridine and tetrahydrobenzene. The constitution of the above compounds is usually deduced directly from their mode of formation, but as certain of them react as tautomeric substances (cf. Ethyl Aceto-acetate) special physical methods have also been used (cf. W. H. Perkin, J. C. S. 1892, 800). F. Aldehydic Monobasic Acids Glyoxalic acid (Ethanal add), glyoxylic acid, CHOC0 2 H, occurs in unripe fruits such as grapes, gooseberries, &c., and may be prepared by superheating dichloracetic acid, CHC1 2 - C0 2 H, with water, 2C1 being here exchanged for 2 (OH), and water being eliminated. It crystallizes in rhombic prisms, dissolves readily in water, and is volatile with steam. The acid and most of its salts contain one molecule of water of crystallization, which points to the formula CH(OH) 2 C0 2 H, analogous to that of chloral hydrate. Glycuronic acid, CHO [CH(OH)] 4 C0 2 H. The lactone of this acid forms colourless crystals, which melt at about 175. The acid itself is obtained from saccharic acid by reduction with sodium amalgam. It is found as a camphor compound in the urine of dogs after camphor is administered to them. G. Monobasic Ketonie Acids Ketonic acids are compounds which contain both a carbonyl and a carboxylic group; they react as acids, and also as ketones; KETONIC ACIDS 223 thus, besides being capable of forming salts, esters, &c., they also combine with sodium bisulphite, yield oximes with hy- droxylamine hydrochloride (see p. 135), are reduced by nascent hydrogen to hydroxy acids, and so on. The most important members of this class are pyroracemic acid, CH 3 COC0 2 H, aceto-acetic acid, CH 3 CO - CH 2 C0 2 H, and Isevulic acid, CH 3 .CO.CH 2 .CH 2 .C0 2 H. Constitution and Nomenclature. The ketonic acids are charac- terized theoretically by the presence of carboxyl and of car- bonyl, the latter being linked to carbon on both sides. They may be regarded either as fatty acids, in which a hydrogen atom of the alkyl group has been replaced by acyl, ECO-, as indicated in the name aceto-acetic acid; laevulic acid is then /5-aceto-propionic acid, and pyroracemic acid is aceto-fonnic acid ; or they may be regarded as derived from the fatty acids by the replacement of the two hydrogen atoms of a CH 2 group by an atom of oxygen. In the latter case aceto-acetic acid is to be designated j3-ketobutyric acid, or butane-3-one-l-acid. This last is the sys- tematic name (Geneva Congress); the expression one indicates the presence of a ketonic group, and the number indicates the relative positions of the ketonic and carboxylic groups. The constitution of a ketonic acid is, as a rule, easy to deter- mine, either from its synthesis or from its transformation into the corresponding hydroxy acids of known constitution by means of nascent hydrogen. The ketonic acids are usually divided into a, /?, and y, or 1, 2, and 3 ketonic acids, according to the relative^positions of the carbonyl and carboxylic groups. CH 3 'CO'C0 2 H, pyro- racemic or pyruvic acid, is a type of an a-acid; CH 3 'CO CH 2 .C0 2 H, aceto-acetic acid, is a type of a /3-acid; and CH 3 .CO.CH 2 .CH 2 .C0 2 H, Isevulic acid, is a type of ay-acid. The a- and y-acids are relatively stable; many can be distilled without undergoing decomposition; but the /3-acids are remark- ably unstable, and readily lose carbon dioxide, yielding ketones. All the ketonic acids on careful reduction yield hydroxy acids. Modes of Formation. I. a-Ketonic acids are formed when the acyl cyanides are hydrolysed (Claisen and SJiadwell) (cf p. 179 and B. 1898, 31, 1023): CH 3 .CO.CN + 2H 2 = CH 3 .(X).C0 2 H4-NH 3 Acetyl-cyanide Pyroracemic acid. The constitution follows from this method of formation. 224 IX. HYDROXY MONOBASIC ACIDS 2. Aceto-acetic and other /3-ketonic acids are obtained as esters by the action of sodium or sodium ethoxide on ethyl acetate and its homologues: 2(CH 3 .CO.OC 2 H 5 ) = CH 3 .CO.CH 2 .CO.OC 2 H 5 + C 2 H 6 OH. According to Claisen and Lowman (B. 20, 651; 26, 2130; 38, 713), the ethyl acetate is first converted by the sodium ethoxide into an additive compound: -C 2 H Na a derivative of ortho-acetic acid (p. 142), which then reacts with another molecule of ethyl acetate, thus: CH 3 = CH 3 . C(ONa) : CH . CO 2 Et+2EtOH CH 3 .C(OH):CH.C0 2 Et CH 3 .CO.CH 2 .CO 2 Et. From the sodium salt thus obtained, the aceto-acetic ester can be liberated by acetic acid, probably first as the enolic com- pound, which is immediately transformed into the ketonic. As shown in the above formation of aceto-acetic ester, one molecule of ethyl acetate reacts with a second molecule. Many reactions of an analogous nature, in which the two reacting molecules are different, may be brought about in the same way by the aid of sodium ethoxide (W. Wislicenus, A. 246, 306). Thus ethyl oxalate and ethyl acetate react in the presence of sodium ethoxide, yielding the sodio derivative of ethyl oxal- acetate: (X) 2 Et.O);pEt+KCH 2 .CO 2 Et = C0 2 Et.CO.CH 2 .CO 2 Et-f EtOH. Esters also readily react with ketones, with the formation of diketones (L. Claisen): CH 3 .CO-OEt + CH 3 .CO.CH 3 = CH 3 .CO-CH 2 .CO.CH 3 + EtOH Acetyl-acetone. When ethyl formate is employed, ketonic aldehydes are not obtained, but their structural isomers, hydroxy-methylene compounds; with acetone, for example, hydroxy-methylene- acetone, thus: H CO OC 2 H 5 +CH 3 CO CH 3 = CH(OH) : CH CO - CH 3 +C 2 H 5 OH Ethyl formate Hydroxy-methylerie-acetone. a-KETONIC ACIDS 225 This condensation between esters, or between esters and ketones, in the presence of sodic ethoxide is usually known as Claisen's reaction, and is of extreme importance as a synthe- tical process. (For summary see B. 1905, 38, 709.) In all cases, according to Claisen, the condensation is pre- ceded by the formation of an additive compound between the sodium ethoxide and the ester. As a rule, metallic sodium and not sodium ethoxide is added to the ester (e.g. to ethyl acetate in the preparation of ethyl aceto-acetate), but the reaction only proceeds when the ester contains free alcohol, and can thus give rise to sodic ethoxide. Quite recently (Ber. 1905, 38, 693) the same chemist has shown that sodamide, NaNH 2 , may be used in place of sodic ethoxide. Michael (B. 1900, 33, 3731, and 1905, 38, 1922) considers that the Claisen condensation proceeds in a different manner, and that it may be compared with the aldol condensation. Compare also Stoermer and Kippe (B. 1905, 38, 1953). 3. Higher homologues of aceto-acetic ester (/3-ketonic acids) are easily obtained from it by the action of sodium ethoxide and alkyl halides (p. 228). 4. Ketonic acids are produced by the cautious oxidation of hydroxy acids containing the secondary alcoholic group: CH 3 .CH(OH).CO.OH + = CH^CO-CO-OH + Lactic acid Pyroracemic acid. a-Ketonic Acids, Pyruvic or pyroracemic acid, GEL- CO* C0 2 H, is a liquid which is readily soluble in water, alcohol, and ether, boils with slight decomposition at 165-170, and smells of acetic acid and extract of beef. It is formed by the dry distillation either of tartaric or of racemic acid, hence its name. In this decomposition carbon dioxide is probably first evolved and gly eerie acid formed: CO ? :H.CH(OH).CH(OH).C0 2 H -> CH 2 (OH).CH(OH).GX3 2 H. This then loses water, yielding pyruvic acid. It may also be obtained by methods 1 and 4. Pyroracemic acid has a tendency to polymerize. Nascent hydrogen reduces it to ethylidene-lactic acid: CH 3 .CO.C0 2 H + 2H = CH 3 .CH(OH).C0 2 H. It is a relatively strong acid owing to the negative nature (B480) ? 226 IX. HYDROXY MONOBASIC ACIDS of the CO group, K = 0*56. It reacts as a ketone with phenyl-hydrazine, hydroxylamine, and hydrogen cyanide. The phenyl-hydrazone crystallizes readily, melts at 192 when quickly heated, and is largely made use of in detecting the acid. The acid also resembles the ketones in the readiness with which it forms condensation products, yielding either benzene derivatives (B. 5, 956), or in presence of ammonia those of pyridine. The electrolysis of a concentrated solution of the potassium salt proceeds in the normal manner, the CH 3 CO COO groups formed at the anode yield diacetyl and carbon dioxide (cf. Electrolysis of potassium-acetate solution), but secondary reactions also occur, and acetic acid is formed to a certain extent. /2-Ketonic Acids. Aceto-aeetic acid, CH 3 .CO.CH 2 -C0 2 II, is a strongly acid liquid, miscible with water, and breaking up into acetone and carbonic acid when warmed. It is prepared by the cautious hydrolysis of its ethyl ester (B. 15, 1376, 1871). Its aqueous solution is coloured violet-red by ferric chloride. The Na- or Ca-salt is sometimes contained in urine (B. 16, 2314). Its constitution as acetone-carboxylic acid follows from the products of decomposition. The ethyl ester, ethyl aceto-acetate, or commonly called aceto -acetic ether, is prepared by the Claisen condensation method (general method 2). It is liberated from the sodium derivative by the addition of acetic acid, and purified by distillation under reduced pressure. It boils at 181, or at 71 under 12'5 mm. pressure, is only slightly soluble in water, but readily in alcohol and ether, and has a pleasant fruity odour. Ferric chloride colours its aqueous solution violet-red. Extremely characteristic are the products to which it can give rise on hydrolysis. 1. Normal Hydrolysis. As an ester, it can be hydrolysed to the corresponding acid and alcohol, viz. aceto -acetic acid and ethyl alcohol. This reaction occurs only when the ester is extremely carefully hydrolysed in the cold with dilute alkali. 2. Ketonic Hydrolysis. This hydrolysis is best accomplished by the aid of dilute sulphuric acid or baryta water, CH 3 .CO.CH 2 .:COOiC 2 H 6 H; iOH, the products being acetone, carbon dioxide, and ethyl alcohol ETHYL ACETO-ACETATE 227 3. Add Hydrolysis. This takes place most readily when the ester is heated with concentrated alcoholic potash or soda, CH 3 .CO: .CH 2 .COO : C 2 H 5 HO;H Hiofe, the products being acetic acid and ethyl alcohol. Ethyl aceto-acetate has been represented by the formula CH 3 CO CH 2 C0 2 Et, and undoubtedly numerous arguments can be brought forward in favour of this constitution; e.g. it reacts with sodic-hydric sulphite, with hydrogen cyanide, and with hydroxylamine as a ketone, and hence should contain the C-CO'C group; a further argument for the ketonic con- stitution is to be found in the decomposition of the acid into acetone and carbon dioxide ; on the other hand, with ammonia or amines it gives /5-amino, or substituted /3-amino crotonic acids, e.g. CH 3 CH(NH 2 ) : CH C0 2 H, and with phosphorus pentachloride it yields /5-chloro-crotonic acid, CH 3 -CC1:CH- C0 2 H. These latter reactions could be most readily explained by assuming the constitution CH 3 C(OH) : CH C0 2 Et, i.e. ethyl /3-hydroxy-crotonate for ethyl aceto-acetate. The ester is thus a typical tautomeric substance, reacting as though it possessed two distinct constitutions, and a study of the chemical proper- ties alone will not, as a rule, permit us to settle with certainty which of the two is the more probably correct. The following suggestions have been made to account for the tautomerism: (a) The ester is really a mixture of the two distinct com- pounds. (b) The pure ester is unstable, and although it may have the one constitution, e.g. ethyl aceto-acetate or ketonic con- stitution, in the presence of various reagents it is readily transformed into the isomeric compound with the enolic con- stitution, i.e. ethyl /3-hydroxy crotonate. This type of tauto- merism is thus often spoken of as keto-enolic tautomerism^ and is frequently met with (see Phloroglucinol, &c.). Accord- ing to this view, it consists in the wandering of a hydrogen atom and a change in position of a double bond (desmotropism). (c) According to Van Laar, the tautomerism is due to an oscillatory hydrogen atom, which cannot be regarded as per- 228 IX. HYDROXY MONOBASIC ACIDS manently attached to C or to 0, but as continually oscillating between the two. Physical methods have been used for elucidating the consti- tution of such compounds. The most important of these are the molecular refraction (Gladstone, Bruhl), the molecular mag- netic rotation (W. H. Perkin, Sen., J. C. S. 1892, 800), and the absorption of electric waves (Drude, B. 1897, 30, 940). [Compare chapter on Relationship between Physical Properties and Chemical Constitution.] The conclusions arrived at from such a study are (a) that ethyl aceto-acetate is a mixture in chemical equilibrium of the ketonic and enolic forms, but con- sists mainly of the ketonic compound, and (b) that a rise of temperature favours the ketonic form. (See also Baly and Desch, J. C. S. 1904, 1029; 1905, 766.) The metallic derivatives are enolic compounds. 1. Ethyl Aceto-acetate as a Synthetical Reagent. One atom of hydrogen in the aceto-acetic ester molecule is readily replaceable by metals (Geuther; Conrad, A. 188, 269). The sodio derivative is formed together with hydrogen on the addition of sodium, and also when an alcoholic solution of the ester is mixed with the calculated amount of sodium ethoxide in absolute alcohol: CH 3 .CO.CHNa.CO 2 Et or CH 3 .C(ONa):CH.CO 2 Et. This sodio derivative forms long needles or a faintly lustrous loose white mass. The copper salt crystallizes in bright-green needles. The sodium is readily replaced by alkyl radicals when the sodio derivative is heated with an alkyl bromide or iodide; sodium bromide or iodide is thus formed together with alky- lated aceto-acetic esters, which are of great interest in various syntheses, e.g.: ethyl methylacetoacetate, CH 3 -CO.CH(CH) 3 . C0 2 C 2 H 5 , and the corresponding ethyl- and propyl-acetoacetic esters, &c. In these compounds the hydrogen atom of the CH rup may be again replaced by Na, and this again substituted alkyl, with the production of dialkylated aceto-acetic esters, e.g.: dimethylacetoacetic ester or ethyl dimethylacetoacetate, CH 3 .CO.C(CH 3 ) 2 .C0 2 C 2 H 5 ; methylethylacetoacetic ester, CH 3 .CO.C(CH 3 )(C 2 H 5 ).C0 2 C 2 H 5 , and so on. These alkylated aceto-acetic esters exactly resemble the mother substance, especially in the manner in which they can be decomposed by either the "ketonic hydrolysis" or the "acid hydrolysis" (cf. p. 226). The formation of ketone ACYL DERIVATIVES OF ETHYL ACETO ACETATE 2^9 largely predominates when dilute acid is employed, and of fatty acids when concentrated alkali is used. In the ketonic hydrolysis the alkyl groups introduced are left attached to a carbon atom of the acetone molecule, e.g. : _ = EtOH + C0 2 + CH 3 .CO.CHMeEt. This affords a very general method for the synthesis of some of the higher ketones. In the acid hydrolysis the alkyl groups remain attached to a carbon atom, which is united to a carboxylic group, e.g. : EtOH. This affords a simple method for synthesising any mono- or dialkylated acetic acid, e.g.: CH 3 CH 2 C0 H ; C 2 H 5 -CH 2 . C0 2 H; (CH 3 )(C 2 H 5 )CH.C0 2 H; (CH 3 )(C 3 H r )CH . C0 2 H. (Cf. Ethyl malonate synthesis, p. 237; also Wislicenus and his pupils, A. 186, 161.) 2. Acyl groups may be introduced in place of alkyl radi- cals into aceto-acetic ester by similar methods, e.g. from acetyl chloride, diaceto- acetic ester, (CH 3 . CO) 2 CH . C0 2 C 2 H 5 . The product obtained varies with the conditions. When an acyl chloride reacts with the sodio-derivative of ethyl acetoacetate the chief product is the C-acyl derivative, viz. (CH 3 CO) (R.CO)CH-C0 2 Et, but when the free ester is treated with an acyl chloride in the presence of pyridine the isomeric 0-acyl derivative is obtained, e.g. R . CO . C . CMe : CH - C0 2 Et. The 0-derivatives, when heated or when warmed with potassium carbonate, are transformed into the isomeric C-compounds. Ethyl chlorocarbonate and the sodio-derivative yield the 0-derivative CH 3 . C(0 C9 2 Et) : CH - C0 2 Et together with a small amount of the C-derivative, aceto-malonic ester, (CH 3 * CO) CH(C0 9 CJEL) 9 ; from monochloracetic ester, CH 2 C1 C0 2 C 2 H 5 , aceto-succinic ester, CH 3 .CO.CH(CH 2 .C0 2 C 2 H 5 ) (C0 2 C 2 H 5 ) may be similarly obtained (see Malonic and Suc- cinic acids, and also the Synthesis of dibasic acids), &c. 3. Iodine acts upon sodio-aceto-acetic ester, yielding diaceto- succinic ester: CH 3 .CO.CHNa.C0 2 C 2 H 5 CH 3 .O).CH.C0 2 C 2 H 6 + l2 "" GH.-CO.CH.CO.C.H. 230 IX. HYDKOXY MONOBASIC ACIDS 4. In addition to the above-mentioned simple syntheses, d number of more complex syntheses may be effected by means of ethyl acetoacetate. Many of these lead to the formation of closed-chain compounds, and will be described in connection with the various groups of ring compounds. The following may be mentioned as the more important: (a) Hantzsch's synthesis of pyridine derivatives, e.g. ethyl dihydrocollidine dicarboxylate, <Me:C(C0 2 Et) >CHMe) !:C(C0 2 Et) by heating ethyl acetoacetate with aldehyde ammonia. (b) The formation of oxyuvitic acid (a benzene derivative), C 6 H 2 (CH 3 )(OH)(C0 2 H) 2 , by the action of chloroform on the sodio-derivative. (c) The formation of methyluracyl by the condensation of ethyl acetoacetate with urea, * nn^ NH 2 i Et OOxnTT nn/ NH CO v nTT ^vXTTT T OTT CV^s^^ 2 " ^-^\"\TTT rVr~<TT\ *&***" ^1 X 2 vXlg \j\J' ^1> 1 \j\\jl)^ (See p. 287 and Synthesis of Uric Acid, p. 291.) (d) The production of furane and pyrrole derivatives by heating ethyl diacetosuccinate (see Synthesis 3) with acids or with ammonia and amines. (e) The synthesis of Phenylmethylpyrazolone Phenyldimethylpyrazolone by the condensation of ethyl acetoacetate with phenylhydra- zine and methylphenylhydrazine respectively. Chlor- and dichlor-aceto-acetic esters, which are very active chemically, are produced by the replacement of the H of the methylene group by Cl. The two methylene hydrogen atoms are also replaceable by the isonitroso group, :N'OH (by the action of NoOA and by the imido group, :NH (cf. A. 226. 294; B. 28, 2683). Laevulic acid, CH 3 . CO CH 2 . CH 2 C0 2 H, forms crystalline plates, melts at 33, and boils at 239. It is formed by the action of acids upon cane-sugar, laevulose, cellulose, gum, starch, and other carbohydrates (A. 175, 181; 206, 207), and has also been prepared synthetically. (For its constitution, cf. A. 256, 314.) It is employed in cotton printing and for the preparation of anti-thermine, &c. DIBASIC ACIDS 231 X. DIBASIC ACIDS Dibasic acids are those which are capable of forming two series of salts, viz. acid and normal, and likewise two series of esters, chlorides, amides, &c. They are characterized by the presence of two carboxyl groups in the molecule. A. Saturated Dibasic Acids, C U H 2U _ 2 4 > OP Acids of the Oxalic Series Name. Formula. Melting-pt. K. Oxalic CO 2 H- C0 2 H- CO 9 H- COgH- CO,H. CO^H. C0 2 H. C0 2 H CH 9 . [CHlo] cnr 'CH; S 'CH 2 ;cH 2 . C0 2 H 2-CO 2 H 3 .C0 2 H 4 -CO 2 H 5 -CO 2 H 6 -C0 2 H )' Sublimes 1 \ 150-160 J 132 185 97'5 149 105 140 10-0 0-016 0-0065 0-0047 0-00371 0-00323 0-00258 Malonic Succinic Grluteivic Adipic Pimelic Suberic . . The above are solid crystalline compounds of strongly acid character, and most of them are readily soluble in water. When heated, they either yield an anhydride, or carbon di- oxide is eliminated and a monobasic acid formed; but most of them can be volatilized in vacuo. Formation. 1. By the oxidation of the di-primary glycols. (See table, p. 204.) la. By the oxidation of hydroxy-acids and, generally, of many complex compounds, such as fats, fatty acids, and carbo- hydrates. 2. By the hydrolysis of the corresponding nitriles; thus, oxalic acid is formed from cyanogen, and succinic acid from ethylene cyanide: (CN) 2 + 4H 2 = (C0 2 H) 2 + 2NH 3 . ) 2 .CN + 4H 2 = C0 2 H.(CH 2 ) 2 -C0 2 H. CN.(CH 2 ) 2 . Since ethylene cyanide is a glycol derivative, its conversion into succinic acid represents the synthesis from a glycol of an acid containing two atoms of carbon more than itself, i.e. the oxcnange of 2 (OH) *or 2'/XX,H), or the indirect combination of ethylene with 2(CO ? H/. 232 x. bl&Aslo 3. By the hydrolysis of the cyano-fatty acids (p. 170), and consequently from the halogen fatty acids also. Thus chloro- or cyaho-acetic yields malonic acid, /3-iodo- (or cyano-) propionic acid, common succinic acid, and a-iodo- (or cyano-) propionic acid, methyl malonic acid. A dibasic acid can therefore be formed from each hydroxy- acid by the exchange of OH for C0 2 H, or indirectly from a fatty acid by the replacement of H by C0 2 H. Thus : 2H-- CH 2 (CN).C0 2 H-> CH 2 (C0 2 H) 2 . 4. The homologues of malonic acid can be prepared from malonic acid itself by a reaction exactly analogous to the aceto- acetic ester synthesis (the "Malonic ester synthesis", p. 238). The dibasic acids are also obtained by means of the aceto- acetic ester synthesis. Aceto-malonic and aceto-succinic acids, which have already been mentioned at p. 229, yield respec- tively malonic and succinic acids by the elimination of acetyl (" acid decomposition "). 5. Higher homologues are obtainable by the electrolysis of the ethyl potassium salts (p. 234) of the simpler dibasic acids, e.g. adipic acid from potassium ethyl succinate. The reaction is exactly analogous to the formation of ethane by the electrolysis of potassium acetate. For example, with potassium ethyl succinate the anions C0 2 Et CH, CH 2 C0, 2 + and kations K are present. When these become discharged at the electrodes during electrolysis, each C0 2 Et CH 2 CH 2 C0 2 group splits up into carbon dioxide and the monovalent radical CO 2 Et CH 2 CH 2 . Two such radicals then combine, yielding ethyl adipate, C0 2 Et CH 2 CH 2 CH 2 CH 2 C0 2 Et. The potas- sium formed at the cathode reacts with the water, yielding hydrogen and potassium hydroxide. The constitution of the acids C n H 2n _ 2 4 is, as a rule, very easy to determine from the above-mentioned modes of for- mation, especially 2, 3, and 4. According to these, one has to decide between the malonic acids proper, i.e. malonic acid and its alkyl derivatives (p. 238), whose two carboxyl groups are both linked to one carbon atom: CH 2 (CO 2 H) 2 , E - CH(CO 2 H) 2 , EE'C(CO 2 H) 2 , and ordinary succinic acid and its homologues, which contain the carboxyls bound to two different carbon atoms. PROPERTIES OF DIBASIC ACIDS 233 The bivalent acid residues, C 2 2 = oxalyl, C 3 H 2 2 = malonyl, and C 4 H 4 2 = succinyl, which are combined with the two hy- droxyls, are termed the radicals of the dibasic acids, and are examples of bivalent acyl radicals. homers. Isomers of oxalic and malbnic acids ate neither theoretically possible nor actually known. We know, how- ever, two succinic acids, viz. : CX) 2 H.CH 2 .CH 2 .C!O 2 H and CH 3 .CH(CO 2 H) 2 . The former corresponds with ethylene chloride and the latter with ethylidene chloride, from which they are respectively derived by the exchange of two chlorine atoms for two car- boxyls. Hence the names ethylene- and ethylidene-succinic acids, or more commonly succinic acid and methylmalonic acid. Since ethylene cyanide can be prepared from the chloride, the above derivation of ethylene-succinic acid is also an experi- mental one. This is not the case, however, with the isomeric acid, since, as a rule, when several chlorine atoms are bound to the same carbon atom, as in ethylidene chloride, they cannot be exchanged for cyanogen. Behaviour. Many of the dibasic acids, in the molecules of which the carboxyls are attached to different carbon atoms, yield intramolecular anhydrides by the elimination of a mole- cule of water from one of the acid. These anhydrides may be obtained either (1) by heating the acids alone, or (2) more generally by the action of phosphorus pentachloride, acetyl chloride, or carbonyl chloride upon the acids (B. 10, 1881; 17, 1285). They recombine slowly with water to form the free acids. This formation of anhydride is favoured by the presence of substituents in the molecule (B. 23, 101, 620; 26, 1925). The elimination of water occurs most readily with succinic and glutaric acids and their substituted derivatives; in fact, with the acids containing a chain of 4 or 5 carbon atoms : C0 2 H.C.C.C0 2 H and C0 2 H.C.C.C. This is undoubtedly to be attributed to the spatial relation- ships of the atoms within the molecule. Assuming that the four valencies of a carbon atom are symmetrically distributed in space (i.e. directed towards the solid angles of a tetra- hedron), then it can be readily seen by the aid of models that in acids of the above types the C0 2 H groups are brought 234 X. DIBASIC ACIDS sufficiently near to one another for water to be eliminated, and for a closed ring to be formed (compare Polymethylene Derivatives). The derivatives of the dibasic acids, i.e. their esters, amides, &c., show precisely the same characteristics as the analogous derivatives of the monobasic acids, especially in the readiness with which they are hydrolysed. DERIVATIVES OF DIBASIC ACIDS Derivatives. Salts. Esters. Chlorides. Amides. CO-ONa CO-OC 2 H 6 CO -01 CO-NH 2 Acid. CO- OH Acid sodium oxalate. CO- OH Ethyl-oxalic acid. CO-O(H) (only known in derivatives). CO- OH Oxamic acid. Neutral or normal. CO-ONa CO-ONa Neutral sodium oxalate. CO-OC 2 H 5 CO-OC,H 6 Ethyl oxalate. CO-C1 CO-C1 Oxalyl chloride. CO-NH 2 'CO-NH 2 Oxamide. As in the case of the glycols, complications arise from the formation of mixed derivatives, e.g. partly ester and partly amide, as in the case of ethyl oxamate (p. 237), and also from the fact that many of the acids form imides. Such imides are derived from the hydrogen-ammonium salts of the acids by the elimination of two molecules of water, thus: Succinic acid Succinimide. Like the amides they are readily hydrolysed (cf. Succini- mide). Oxalic acid (Ethane diadd), (C0 2 H) 2 , 2H 2 0, is one of the oldest known organic acids, and occurs as its acid potassium salt in many plants, especially in Oxalis Acetosella (wood-sorrel), and in varieties of Rumex, and as the free acid in varieties of Boletus, as normal sodium salt in varieties of Salicornia, and as calcium salt in rhubarb root, &c. It may be prepared by a variety of different reactions. at 360 C the direct co bination of carbon dioxide with sodium 4 Na 2 . OXALIC ACID 235 2. By quickly heating sodium formate to a high tem- perature: 2HC0 2 Na = H 2 + C 2 4 Na 2 . 3. It is often met with as an oxidation product of relatively complex carbon compounds, e.g. by the oxidation of alcohol by permanganate, and of sugar, starch, wood, &c., by nitric acid. The oxidation of cane-sugar with concentrated nitric acid is often employed for the preparation of pure oxalic acid. The crystallized acid readily separates when the liquid is cooled or evaporated. 4. On the commercial scale, oxalic acid is manufactured by the fusion of cellulose (see Carbohydrates) in the form of saw- dust with a mixture of sodium and potassium hydroxides at 200-220 in flat iron pans. The sodium and potassium oxalates are extracted with water, then precipitated as calcium oxalate, and finally converted into the acid by treatment with the requisite amount of sulphuric acid. It crystallizes from water in large, transparent, monoclinic prisms containing two molecules of water of crystallization. They slowly effloresce in the air, and readily become an- hydrous when heated at 100. At higher temperatures the acid partly decomposes into carbon dioxide and formic acid, and partly sublimes unaltered. The acid is readily soluble in water, moderately in alcohol, and somewhat sparingly in ether. The aqueous solution de- composes when exposed to light. Concentrated sulphuric acid decomposes it into carbon mon- oxide, carbon dioxide, and water: C 2 H 2 O 4 = CO 2 Oxalic acid is stable as regards nitric acid and chlorine, but permanganate of potash or manganese dioxide in acid solution oxidizes it to carbonic acid: C 2 H 2 4 + = 2C0 2 + H 2 O. It is reduced by nascent hydrogen to glycollic acid. The strength of an aqueous solution of the acid may bo determined by titration with standard alkali, using phenol phthalein as indicator, or by means of standard permanganate in the presence of sulphuric acid. Its salts are known as oxalates. The alkaline salts, both acid and normal, are readily soluble in water, the normal sodium 236 fc. DIBASIC salt being the least so. The " salt of sorrel " of commerce is a mixture of C 2 O 4 HK and a salt, C 2 4 HK + C 2 4 H 2 + 2H 2 (cf. p. 144). The calcic salt, C s 4 0a + H 2 (or 3H 2 0), is insoluble in water arid acetic acid, and serves for the recog- nition of oxalic acid. Ferrous-potassic oxalate, (C 2 4 ) 2 FeK 2 + H 2 0, finds application in photography as a powerful reduc- ing agent (the "oxalate developer ). Ethyl oxalate, (COOC 2 H 6 ) 2 , which can be directly pre- pared from the anhydrous acid and ethyl alcohol without a catalytic agent, is liquid, while methyl oxalate, (COOCH 3 ) 2 , is a solid, crystallizing in plates which melt at 54; both of them possess an aromatic odour, distil without decomposition, and are extremely readily hydrolysed. Partial hydrolysis, with alcoholic potash solution, produces potassium ethyl-oxalate, COOK-COOC 2 H 5 , from which the free ethyl -oxalic acid, COOH COOC 2 H 5 , which is readily hydrolysed, and its chloride, ethyl-oxalyl chloride, COC1 . COOC 2 H 5 , can easily be prepared. Oxalic ester yields, with an excess of ammonia, oxamide, and with one equivalent the mixed derivative, am- monic oxamate, COONH 4 .CQ.NH 2 . Oxalyl chloride, (COC1) 2 , has been obtained by the action of excess of phosphorus pentachloride on ethyl oxalate. It is a liquid, b.-pt. 70, and has a pungent odour (B. 41, 3558). Oxamide, NH 2 COCONH 2 , the normal amide of oxalic acid, is obtained, among other methods, by the distillation of ammonium oxalate, by the partial hydrolysis of cyanogen, but is most readily obtained by the addition of ammonium hydroxide solution to ethyl oxalate. It is a white crystalline powder, is readily hydrolysed, and by the abstraction of water may be converted into cyanogen. When heated it sublimes unchanged. Oxamic acid, NH 2 CO CO OH, the amic acid correspond- ing with oxalic acid, is prepared by heating ammonium hy- drogen oxalate. It is a crystalline powder, sparingly soluble in cold water, possesses acid properties, and yields salts, esters, &c. It melts and decomposes at 210. Ethyl oxamate, oxamethane, NH 2 CO CO OC 2 H 5 , is a crys- talline compound, and melts at 114-115. The action of PC1 5 on this compound is first to form NH 2 CC1 2 - CO OC 2 H 5 , ethyl-examine chloride, which re,-idily loses hydrogen chlo- ride yielding NH : CC1 CO . OC 2 H 5 and finally NjC-Cp. OC 2 H 5 , cyano- carbonic ester. Corresponding with oxamide we have dimethyl-oxamide, CH 3 . NH . CO . CO . NHCH 3 , and MALONICJ ACID 237 r corresponding with oxamethane, ethyl - dimethyl - oxamate, (CH 3 ) 2 N CO CO OCgHg, both of which were mentioned at p. 106. Oximide, -^NH, is prepared by the action of PC1 5 upon oxamic acid. It forms colourless prisms readily soluble in water and of neutral reaction, is quickly hydrolysed by hot water, and is transformed into oxamide by the action of am- monia (B. 19, 3228). Cyanogen, N:C-C:N, is the nitrile corresponding with oxalic acid (see p. 265). Malonic acid, Propane diadd, CH 2 (C0 2 H) 2 , occurs in beet- root as its calcium salt, and may be obtained by the following methods : ^(1) By the oxidation of malic acid by means of chromic acid, hence its name; (2) by the hydrolysis of malonyl-urea (p. 288), (Baeyer}-, (3) by the hydrolysis of cyano-acetic acid (Kolbe, Milllei-, A. 131, 348; 204, 121): CN.CH 2 .C0 2 H + 2H 2 = CH 2 (CO 2 H) 2 + NH 3 . It crystallizes in large plates, dissolves readily in water, alcohol, and ether, melts at 132, and decomposes when heated to a slightly higher temperature. Ethyl malonate, malonic ester, CH 2 (CO OC 2 H 5 ) 2 , is usually obtained by passing hydrogen chloride into a solution of cyano- acetic acid (from chloracetic acid) in absolute alcohol. It is a liquid of faint aromatic odour boiling at 198, and having a remarkable similarity to aceto-acetic ester. Thus the hydro- gen of the methylene group is replaceable by sodium, through the influence of the carbonyl groups CO, which are also bound to the methylene; and the resulting sodio-malonic ester readily exchanges the metal for alkyl when treated with an alkyl iodide. By this means the higher homologues of ethyl malonate, e.g. methyl-, ethyl-, propyl-, &c., malonic esters, are obtained. Further, the second hydrogen atom in these can be exchanged in exactly the same manner for sodium and then for alkyl, whereby dialkyl malonic acids are formed. This so-called "malonic ester" synthesis is an important method for the preparation of the higher dibasic acids, being applicable even in complicated cases. (Cf. Conrad and Bischoff, A. 204, 121.) It is also of importance for the preparation of some of the higher fatty acids, as the substituted malonic 238 X. DIBASIC ACIDS acids when heated above their melting-points lose carbon dioxide and yield fatty acids: When ethyl malonate is heated with its sodium compound, a derivative of phloroglucinol is formed. (See this.) Malonic anhydride, carbon suboxide, C 3 2 , 0:C:C:C:0, is formed when malonic acid is heated in a suitable apparatus at 140-150. (Diels and Wolf, B. 1907, 40, 355; cf. also 1906, 39, 689; Standinger and St. Bereza, B. 1908, 41, 4461.) The yield is only 10-12 per cent, and acetic acid and carbon dioxide are also formed. It is a colourless liquid, b.-pt. -\- 7, m.-pt. 107, and Dj I'll. It reacts readily with water, hydrogen chloride, dry ammonia, and aniline, yielding respectively mal- onic acid, malonyl chloride, malonamide, and malonanilide. It is stable at low temperatures, but decomposes rapidly at 100. Succinic acid, Butane diacid, ethylene-succinic add, symmetriwl ethane-dicarboxylic acid (from succinum = amber), C0 2 HCH 2 - CH 2 C0 2 H. This acid has been known for a long time; its composition was determined by Berzelius. It exists in amber, in various resins and lignites, in many Composite, in Papa- veraceae, in unripe wine grapes, urine, blood, &c. It may be obtained by most of the general methods described on p. 231, e.g.-. 1. By the hydrolysis of ethylene cyanide. This is an extremely important method, as it affords a synthesis of succinic acid and also establishes its constitution, since it can be shown that in ethylene dibromide the two bromine atoms are attached to distinct carbon atoms: CH 2 :CH 2 CH 2 Br.CH 2 Br CN-CHo-CHo-CN ^* C0 2 H.CH 2 .CH 2 .C0 2 H. 2. From ^-iodo-propionic acid by conversion first into /5-cyano-propionic acid and subsequent hydrolysis. 3. By the reduction of f umaric and maleic acids, C0 2 H CH : CII-C0 2 H. 4. By heating its hydroxy- acids, malic or tartaric, with hydriodic acid: = C0 2 H.CH 2 .CH 2 .CO 2 H+I 2 . 5. It may also be obtained by the fermentation of the salts of these hydroxy-acids by means of certain micro-organisms, e.g. certain species of bacteria, SUCCINIO ACID 239 It is also formed in small quantities as a by-product in the alcoholic fermentation of sugar, and by the oxidation of fats, fatty acids, and paraffins by means of nitric acid. It is usually prepared from calcic malate according to 5, or by the distillation of amber. 6. It may also be synthesised from ethyl malonate. The sodio- derivative of this ester reacts not merely with alkyl iodides or bromides, but also with the esters of haloid fatty acids, e.g. ethyl bromoacetate. (C0 2 Et) 2 CHNa + Br.CH 2 .CO 2 Et = NaBr + (CO 2 Et) 2 . CH . CH 2 . CO 2 Et. The product is ethyl ethane-tricarboxylate, and when this is hydrolysed, alcohol, carbon dioxide, and succinic acid are formed. This method is of general interest, as various sub- stituted succinic acids may be synthesised by this method. In place of sodio-ethyl malonate, the sodio-derivatives of esters of mono-substituted malonic acids may be used, and in place of ethyl bromo-acetate the esters of other halogen fatty acids, e.g. ethyl iodo-propionate or ethyl bromo-valerate. It has recently been shown (Bone and Sprankling, J. C. S. 1899, 839) that better yields can be obtained by using ethyl cyano-acetate and its derivatives in place of ethyl malonate and its derivatives. Properties. It crystallizes in monoclinic prisms or plates with an unpleasant faintly acid taste, is readily soluble in water, melts at 185, and boils at 235, but is at the same time partially converted into its anhydride. (For its electro- lysis, see pp. 46 and 232.) Is very stable towards oxidizing Of the salts of succinic acid, the basic ferric salt, obtained by the addition of a ferric salt to ammonium succinate, is used in analysis for the separation of the ferric and aluminic radicals. The calcic salt is soluble in water. The derivatives of succinic acid correspond closely with those of oxalic, e.g. succinamic acid, NH 2 CO CH 2 CH 2 CO -OH, is analogous to oxamic acid, and succinamide, NH 2 CO CH 2 CH 2 CO NH 2 , to oxamide. There also exists, as in the case of other dibasic acids, an imide, succinimide, C 2 H 4 <f!c)>NH. The latter crystallizes in rhombic plates, and is formed by heating ammonium hydrogen succinate. The basic properties of the NH are so modified by the two carbonyl groups of the acid radical that the imido-hydrogen is 240 X. DIBASIC ACIDS replaceable by metals, such as K, Ag, &c. (Cf. B. 25, Kef. 283.) Succinyl chloride reacts as though it were dichloro- butyro-lactone, C 2 H 4 ^QQ_^>0. It is a colourless liquid boiling at 190, and is obtained by the action of phosphorus pentachloride (2 mols.) on the acid, or of 1 mol. on the anhy- dride. In many of its properties it resembles the acid chlorides, but on reduction yields butyro-lactone ; with benzene and alu- minium chloride it yields mainly y-diphenyl-butyro-lactone, PPh , and with zinc ethyl y-diethyl-butyro-lactone. The chloride is probably a mixture of dichloro-butyro-lactone with a small amount of the normal chloride. Succinic an- PO hydride, C 2 H 4 <^pQ^>0, is best obtained by the action of acetic anhydride on the acid. It crystallizes in glistening plates, melts at 120, and distils without decomposition. It slowly combines with water, yielding the acid; more readily with alkalis, and also with alcohols at a higher temperature, yield- ing the acid esters, e.g. HO.CO-CH 2 .CH 2 .CO.OEt. This is the most convenient method for the preparation of acid esters. The other methods sometimes employed are: (a) the partial hydrolysis of the neutral ester, and (b) the partial esterifi- cation of the acid by means of very dilute solution of hydrogen chloride in the requisite alcohol (Bone, Sudborough, and Spunk- ling, J. C. S. 1904, 534). Of the higher acids the following are of interest : Glutaric acid, Pentane diacid, C0 2 H-CH 2 .CH 2 .CH 2 .C0 2 H. It may be obtained from glutamic acid (p. 249), and also by condensing formaldehyde with ethyl malonate in the presence of a small amount of diethylamine : CH 2 :O + 2H-CH(C0 2 Et) 2 (CO 2 Et) 2 .CH.CH 2 .CH(CO 2 Et) 2 . This is a further example of the readiness with which alde- hydes condense with compounds containing a methylene group adjacent to carbonyl or negative groups. The product, ethyl propane-tetracarboxylate, on hydrolysis yields ethyl alcohol, carbon dioxide, and glutaric acid. The last crystallizes in prisms, melts at 97, is readily soluble in water, and yields an anhydride, an imide, &c. The imide can be obtained when piperidine is oxidized with hydrogen peroxide, and when distilled with zinc dust yields a small amount of pyridine, UNSATURATED DIBASIC ACIDS 241 Isomeric with glutaric acid is methyl-succinic or pyro- tartaric acid, C0 2 H . CHMe CH 2 C0 2 H, an acid closely resembling succinic acid, and obtained by dry distillation of tartaric acids. The s- dimethyl- and s-dibromo- succinic acids, C0 2 H CHBr'CHBrC0 2 H, occur in the same number of stereo- isomeric modifications as the tartaric acids (p. 249). Mono- and dibromo-succinic acids, C 2 H 3 Br(C0 2 H) 2 and C 2 H 2 Br 2 (C0 2 H) 2 , are easily prepared, and are valuable for the syntheses of the hydroxy-succinic acids. Sodium reacts with ethyl succinate, yielding ethyl succinylo- succinate, a compound related to benzene. Isosuccinic acid, Methyl - propane diacid, ethylidene - succinic add, or methyl -malonic acid, CH 3 CH(C0 2 H) 2 , is formed by the malonic ester synthesis, or from a-chloro- (or iodo-) pro- pionic acid (pp. 237 and 232). It is a solid, when heated decomposes into C0 2 and propionic acid, and yields no an- hydride (p. 234). Relative strengths of the dibasic acids: K Oxalic 10-0 (about) Malonic 0'163 Succinic 0'0066 Glutaric 0'0047 The strengths of alkylated succinic acids are not so very different from that of succinic acid, and those of alkyl glutaric acids are of the same order as that of glutaric. B. Unsaturated Dibasic Acids The unsaturated acids stand in the same relation to the saturated dibasic acids as acrylic acid does to propionic. As dibasic acids they yield derivatives analogous to those of oxalic acid, while as unsaturated compounds each molecule possesses, in addition, the property of combining with two atoms of hy- drogen or halogen, or with one molecule of halogen hydride. Common Methods of Formation. 1. By the elimination of water from the hydroxy dibasic-acids. Thus malic acid when distilled yields water and maleic anhydride, which volatilizes, and also fumaric acid, which remains behind : CO 2 H.CH(OH).CH 2 .CO 2 H - H 2 O = CO 2 H.CH:CH.CO 2 H. The actual product obtained by the elimination of water (U480) Q 242 X. DIBASIC ACIDS from malic acid varies considerably with the conditions of the experiment. Thus, when malic acid is maintained at a temperature of 140-150 for some time, the chief product is fumaric acid; when the malic acid is rapidly -heated at a higher temperature, maleic anhydride is largely formed. Citric acid yields, in a similar way, C0 2 , H 2 0, itaconic acid, CH 2 :C(C0 2 H).CH 2 .C0 2 H, and citraconic anhydride (methyl- maleic anhydride). 2. By the separation of halogen hydride from the mono- haloid derivatives of succinic acid arid its homologues, e.g. monobromo-succinic acid yields fumaric, thus: CO 2 H.CHBr.CH 2 .CO 2 H-HBr = CO 2 H.CH:CH.CO 2 H. 3. Fumaric acid has been prepared synthetically from acetylene di-iodide, just as succinic acid has been from ethy- lene dibromide. Constitution. The acids of this series may be regarded as dicarboxylic acids of the olefines, e.g. fumaric and maleic acids, C 2 H 2 (C0 2 H) 2 , as those of ethylene. Their mode of formation 1 corresponds exactly with the production of ethylene from alcohol, or with that of acrylic from ethylene lactic acid, while 2 agrees with that of ethylene from ethyl iodide. Maleic acid (ds-Butene diacid), C0 2 H.CH:CH.C0 2 H, crys- tallizes in large prisms, possesses a grating, nauseous acid taste, and is very readily soluble in cold water. It distils unchanged, excepting for partial transformation into maleic anhydride. It is conveniently prepared by heating the acetyl derivative of malic acid (see p. 247), or from fumaric acid and POC1 8 (A. 268, 255). Fumaric acid (trans-Butene diacid), C 2 H 2 (C0 2 H) 2 , crystallizes in small prisms with a strong, purely acid taste, and is almost insoluble in cold water. It does not melt, but sublimes at about 200 with formation of maleic anhydride. It occurs in Fumaria offidnalis, various fungi, truffles, Iceland moss, &c., and is obtained from maleic acid either by prolonged heating of the latter at 130, or by the action upon it of hydrobromic or other acids. (For its preparation, see A. 268, 255.) Both acids are converted into esters when their silver salts are heated with alkyl iodide, and these esters stand in very close relationship to one another, as do the free acids; thus ethyl maleate is changed into ethyl fumarate when warmed with iodine, and the latter ester is formed by saturating an alcoholic solution of maleic acid with dry hydrogen chloride. STEREO-CHEMISTRY OF UNSATURATED DIBASIC ACIDS 243 Isomerism of Funiaric and Maleic Acids. The isomerism of these two acids is a problem which has attracted the atten- tion of numerous chemists. Attempts were first made to account for the difference by polymerism or structural iso- merism, e.g. Fittig has suggested CO 2 H.CH:CH.CO 2 H and C0 2 H.CH 2 .C-C0 2 H; A but isomerism of this type is impossible, since both acids when oxidized yield one or other of the tartaric acids C0 2 H CH(OH) CH(OH) . C0 2 H. Anschutz has brought forward the formulae CH-CO , CO 2 H.CH:CH.CO 2 H and || >O. CH.C(OH)/ Such a formula as the latter is not at all probable, as in this case maleic acid, which is the stronger acid (K = 1'17, and for fumaric K = 0'093), would not possess a carboxylic, but merely a hydroxy lactone structure (PFegscheider, B. 1903, 36, 1543). This formula is also found to be quite unten- able when the products of bromi nation and of oxidation are considered. The fact that the two acids are structurally identical, and must both be represented as ethylene dicarboxylic acids, is now generally recognized, and the conclusion is largely based on the following facts: (1) Both acids when reduced with sodium amalgam yield ordinary succinic acid. (2) Both acids combine with hydrogen bromide, yielding the same bromo- succinic acid. (3) Both acids combine with water at moderate temperatures, yielding the same malic acid. In most of these additive reactions the maleic acid reacts somewhat more readily than the fumaric, and is at the same time partially transformed into fumaric. (4) When carefully oxidized, the two acids yield stereo-isomeric tartaric acids, maleic being transformed into meso-tartaric, and fumaric into racemic acid.^ (5) Simi- larly, on addition of bromine they yield stereo-isomeric di- bromo-succinic acids. As the two acids are structurally identical, the isomerism can only be accounted for by a different spatial relationship of the atoms within the molecule. The stereo-isomerism of these unsaturated compounds is quite distinct from that of the saturated compounds, such as lactic and tartaric acids. 244 X. DIBASIC ACIDS We are forced to assume that in saturated compounds where two C atoms are united by a single bond, there is free rotation around the axis represented by the bond; otherwise, the number of isomerides Cabc-Cdef, or even Caab-Caab, would be much greater than what is actually found. When, however, the two carbon atoms become united by a so-called double bond, free rotation is completely prevented, and we have the centres of gravity of the two C atoms and of the four substituents all lying in the same plane, viz. the plane of the paper, e.g. C 2 H 4 may be represented as H-C-H H.C.H. No stereo-isomerism is possible with such a compound, nor yet with any compound in which the 2 radicals attached to the one carbon atom are the same, e.g. CH 2 :CC1C0 2 H; but immediately each carbon atom has 2 different radicals attached to it, isomerism is theoretically possible, e.g. crotonic acid, CH 3 .CH:CH.C0 2 H, and maleic acid, C0 2 H . CH : CH . C0 2 H, viz.: CH 3 .C-H CH 3 .C-H C0 2 H.C.H H.C.C0 2 H, C0 2 H-C.H C0 2 H.C.H C0 2 H.C.H H.C.C0 2 H; and similarly for oleic and elaidic acids, erucic and brassidic acids, cinnamic and allocinnamic acids and its derivatives, and also for numerous other compounds. As the centres of gravities of the carbon atoms and of their substituents all lie in one plane, the molecules are not perfectly asymmetric, and therefore possess no optical activity, and cannot be resolved into optically active components. The two isomerides are not so closely related to one another as d- and /-valeric acids, or as d- and Z-tartaric acids; as a rule, they differ entirely as regards their ordinary physical pro- perties, e.g. crystalline form, solubility, melting-point, water of crystallization, dissociation constant, &c., and in many cases considerable differences in chemical properties are met with, e.g. maleic acid yields an anhydride and fumaric acid does not. As a rule, one of the isomerides is less stable than the other, and under suitable conditions, e.g. influence of (a) heat, STEREO-CHEMISTRY OF UNSATURATED DIBASIC ACIDS 245 (b) light, (c) chemical reagents, especially small amounts of halogens or halogen hydracids, the labile compound is trans- formed into the stable. With certain pairs of isomerides the transformation is mutual, so that whichever of the two we start with we obtain, under the conditions enumerated above, a mixture of the two in chemical equilibrium. As examples of the transforming action of heat we have the following : Fumaric -* maleic; allocinnamic cinnamic; angelic tiglic, and either chloro-fumaric, C0 2 H-CC1:CH. C0 2 H, or chloro-maleic acid heated separately yields a mixture of the two. The effect of exposure to sunlight is often identical with the action of heat, but not always so, e.g. ethyl benzyl- aminocrotonate, Q H p h ^ -^ j|^>C : CH C0 2 Et, exists in two stereo-isomeric modifications melting at 79 and 21; the effect of heat is to transform the higher melting ester into the lower melting, and the effect of sunlight is the exact opposite. As examples of the influence of chemicals, we have the action of small amounts of nitrous acid in transforming oleic into elaidic and erucic into brassidic acids. Similarly, small amounts of bromine will transform dimethyl maleate into dimethyl fumarate. Skraup has shown that either sulphur dioxide or hydrogen sulphide alone is unable to transform maleic into fumaric, but that a mixture of the two will bring about the transformation. The chemical reaction between the H 2 S and S0 2 may be re- garded as a type of detonator which starts the transformation in the maleic acid. All chemical reactions, however, cannot act in the same manner as catalysts. It has also been shown that the salts of maleic acid, e.g. copper maleate, when decom- posed by hydrogen sulphide yield fumaric acid or a mixture of fumaric and maleic acids, although, as stated above, the sulphide itself is incapable of transforming free maleic acid into fumaric. The exact method of transformation is not known. It may be (a) that the two radicals attached to the one carbon atom actually exchange positions directly; (b) the two carbon atoms may not be entirely unable to rotate round their common axis, but may only be in a state of strain, and under the influence of light, heat, &c., a rotation through an angle of 180 may occur; or (c) in the case of change brought about by chemical agents it is possible that the agent employed first forms an additive compound and is subsequently removed, 246 X. DIBASIC ACIDS but this view has been shown to be impossible in many cases by Anschiitz, Fittig, and Michael. The system of nomenclature adopted to distinguish between the two isomerides is to term the compound in which two similar substituents are on the same side of the molecule the cis compound, and the isomeride in which the two similar radicals are on opposite sides of the molecule the trans: C0 2 H.C-H C0 2 H.C-H C0 2 H.C-H H.C.C0 2 H cw-Ethylene dicarboxylic acid trans-Ethylene dicarboxylic acid. In cases where it has not been found possible to ascertain which of the two known compounds has the cis configuration and which the trans, the ordinary name is given to the one and the prefix iso, or better, allo, to the other, e.g. crotonic and isocrotonic acids, cinnamic and allocinnamic acids. Determination of Configuration. In the case of fumaric and maleic* acids this has been accomplished with a considerable degree of certainty. The arguments used for the cis con- figuration of maleic and the trans configuration of fumaric are briefly : (a) Maleic acid when heated, or treated with dehydrat- ing agents, readily yields an anhydride (cf. Succinic anhydride), CH-CCK />0, which can combine with water to re-form maleic acid. Fumaric acid yields no distinct anhydride of its own. (b) Maleic acid when oxidized yields meso-tartaric acid, whereas fumaric acid yields racemic acid (see p. 252) : CO 2 H H.C.C0 2 H H-j-OH H.n.C0 2 H H4-OH C0 2 H. CO 2 H CO 2 H H.C.C0 2 H HfOH d OH-J-H C0 2 H.C.H C0 2 H-M)E OH-f(X) 2 H Th3 configurations of other pairs of olefine stereo-isomerides have not been determined with the same degree of certainty, and many of the methods described in text-boots as being available for this purpose cannot be relied on, e.g. of two HYDftOXY DIBASIC ACIDS 247 stereo-isomeric a- or /Mialogenated compounds, the one which has the halogen in the czs-position with respect to a hydrogen atom will lose halogen hydracid more readily under the influence of alkali, e.g. : CH 3 .C.Br CH 3 .C.Br H.C.C0 2 H In many cases it is probable that exactly the reverse holds good. An admirable account of the stereochemistry of olefine derivatives will be found in Werner's " Stereochemie ", 1904 pp. 179-227. For higher homologues, see Fittig, B. 26, 40. Acetylene-dicarboxylic acid, Butine diacid, C0 2 HC:C' C0 2 H, is a type of an acetylenic acid; it is obtained by the elimination of two molecules of hydrogen bromide from one of dibromo-succinic acid. It possesses the characteristic proper- ties of a dibasic acid, and also of an unsaturated compound, but does not yield metallic derivatives of the type of silver acetylene. It readily loses carbon dioxide, yielding propargylic acid, CH:C-C0 2 H. Diacetylene-dicarboxylic acid, C0 2 H- C:C'CiCC0 2 H, and tetracetylene-dicarboxylic acid, Deca- tetrine diacid, C0 2 H .CiC-CiC-CiC-CiO. C0 2 H, have been prepared by Baeyer (B. 18, 678 and 2269). With increasing length of chain they show an increasing tendency to explode. (For Baeyet's theory of explosions, see B. 18, 2277.) C. Hydroxy Dibasic Acids 1. Tartronic acid, Propanol diacid, hydroxy-malonic acid, OH- CH.(C0 2 H) 2 , forms large prisms (-f ^H 2 0), and is ^ easily soluble in water, alcohol, and ether. It cannot be distilled unchanged, since it breaks up on heating into carbon dioxide and glycolide. As hydroxy-malonic acid it may be prepared by the action of moist silver oxide on chloromalonic acid. It may also be obtained by the reduction of the corresponding ketonic acid, mesoxalic acid, CO(C0 2 H) 2 , and also by the oxidation of glycerol with permanganate. 2. Malic acid, Butanol diacid, hydroxy-succinic acid, C0 2 H- CH 2 .CH(OH).COJS (Scheele, 1785), is very widely distributed in the vegetable kingdom, being found in unripe apples, sorb- apples, grapes, barberries, mountain-ash berries, quinces, &c. 248 X. DIBASIC ACIDS Some of the simpler methods of formation are quite analogous to those employed in the case of hydroxy monobasic acids, e.g. (1) by the action of moist silver oxide on bromo-succinic acid; (2) by the reduction of tartaric or racemic acid with HI, and of oxal-acetic acid (pp. 224 and 260) with sodium-amalgam; (3) by the action of nitrous acid on the corresponding amino acid, aspartic acid; and (4) by the addition of the elements of water to fumaric or maleic acid under the influence of aqueous sodic hydroxide. It crystallizes in hygroscopic needles, is readily soluble in water and alcohol, but only sparingly in ether. It melts at 100, and when it is distilled, maleic anhydride passes over and fumaric acid remains in the retort (p. 241). K = 0'04. The molecule of malic acid contains an asymmetric carbon atom, and thus the acid should exist in two optically active and a racemic modification. The acid obtained from natural sources, Z-malic acid, is Ia3vo-rotatory in dilute solution, but the rotation diminishes as the concentration increases. With a 34-per-cent solution at 20 no optical activity is shown, and with more concentrated solutions dextro-rotation is exhibited. The acid obtained synthetically is optically inactive and constitutes the racemic form, and it has been resolved into optically active modification by the usual methods (p. 254), (B. 1898, 31, 528). The alkali salts and the acid calcium salt of malic acid are readily soluble in water, while the normal calcium salt is only sparingly soluble. The constitution follows from its methods of preparation, from the fact that it is readily reduced to succinic acid, and that its esters react with acetic anhydride, yielding mono- acetyl derivatives. Amides and Amines of Malic Acid. Like glycollic acid, malic acid forms as an acid amides (saponifiable), and as an alcohol an amine (not saponifiable). The amides are: Malamide, NH 2 .CO.CH(OH).CH 2 .CO.NH 2 , crystallizing in prisms, and malamic acid, C0 2 H.CH 2 .CH(OH).Cp-NH 2 , the latter being only known as ethyl ester. The amino-acid, aspartic acid, C0 2 H CH(NH 2 ) - CH 2 CO 2 H, unites in itself, like glycocoll, the properties of a base and of an acid, but the acid character predominates. Its acid amide, asparagine, CO 2 H.CH(NH 2 ).CH 2 .CO.NH 2 , which is isomeric with mal- amide, is very widely distributed in the vegetable kingdom, being present in the young leaves of trees, in beet-root, potatoes, the shoots of peas, beans, and vetches, and in ASPARTIC ACID. TARTARIC ACID 249 asparagus; it was first found in the last-named vegetable in the year 1805. It forms glistening rhombic prisms (+ H 2 0), is readily soluble in hot water, but insoluble in alcohol and ether, and yields aspartic acid when hydrolysed. It is leevo- rotatory. A dextro-rotatory asparagine has likewise been obtained from the shoots of vetches (B. 20, Ref. 510); it possesses a sweet taste, and unites with the laevo-rotatory compound to an inactive modification. For the synthesis of the asparagines and their constitution, see Piutti, B. 22, Ref. 241 and 243. Aspartic acid, amino-succinic add, is present in beet molasses, and forms an important product of the decomposition of proteids with acids or alkalis. It has been synthesized, e.g. from bromo-succinic acid and ammonia, and crystallizes in small rhombic plates readily soluble in hot water. It exists in optically active modifications, which differ in taste and are convertible the one into the other (B. 20, R. 510). Nitrous acid transforms both aspartic acid and asparagine into malic acid. Glutainic acid, a-amino-glutaric acid, C0 2 H CH(NH 2 ) CH 2 CH 2 ^C0 2 H, and glutamine correspond with aspartic acid and asparagine. The former is found in beet-root and in the shoots of the vetch and gourd, while the latter is produced, together with aspartic acid and leucine, by boiling proteids with dilute sulphuric acid. D. Dihydroxy Dibasic Acids These acids are characterized by the presence of two hy- droxyl radicals in the molecule in addition to two carboxyls. Tartaric acid, Butane -diol diacid, dihydroxy - succinic add, C0 2 H . CH(OH) . CH(OH) (C0 2 H), exists in four distinct modifications. 1. d- or Dextro-tartaric acid, m.-pt. 170. 2. /- or Laevo-tartaric acid, anti-tartaric add, m.-pt. 170. 3. Racemic acid, d-l-tartaric add, para-tartaric add, m.-pt. 206. 4. i- or Inactive tartaric acid, meso-tartaric add, m.-pt. 143. The constitution of these acids follows from their relation- ship to succinic acid, from their methods of formation, and from the fact that their esters with acetic anhydride yield diacetyl derivatives. Solutions of equal concentration of the two first of these 250 X. DIBASIC ACIDS acids turn the plane of polarization of light in an equal degree, but in opposite directions. By their union the in- active racemic acid is formed, and this can, conversely, bo separated into its components. The fourth tartaric acid, likewise inactive, cannot be resolved in this way. The common tartaric acid found in nature is optically active, and is the ^-tartaric acid, whereas the acids obtained synthetically are optically inactive, viz. racemic acid or meso- tartaric acid, or a mixture of both, e.g. dibromo-succinic acid with moist silver oxide yields a mixture of racemic and meso- tartaric acids. Fumaric acid when oxidized with permanganate is converted into racemic acid, and maleic acid by a similar process into meso-tartaric acid (p. 246). Glyoxal cyanhydrin (p. 221) when hydrolysed yields racemic acid, and finally, mannitol when oxidized with nitric acid yields racemic acid, and sorbitol meso-tartaric acid. Synthesis : CH 2 :CH 2 - CH 2 Br.CH 2 Br - CN.CH 2 .CH 2 -CN Br KCN C0 2 H.CHBr.CHBr.C0 2 H Hydrolysis Br 2 C0 2 H.CH(OH).CH(OH).C0 2 H. AgOH Stereo-isomerism of the Tartaric Acids. The isomerism of the tartaric acids is of much the same type as that discussed in the case of active valeric and of a-lactic acid. A glance at the constitutional formula for the acids shows the presence of 2 asymmetric carbon atoms; to each of these 2 atoms are attached the radicals H, OH, and C0 2 H, and the remaining valency of each carbon is employed in attaching it to the other carbon atom. A compound of this general type, C(a, b, c) C(a, b, c), is known as a compound containing 2 similar asymmetric carbon atoms. If one valency of each carbon is employed in uniting the 2 carbon atoms together, then the 3 radicals, a, b, c, which are attached to the remaining three valencies of a carbon atom, may be arranged in two distinct ways, viz. a ~^ , positive order, and V' , negative order. STEREO-CHEMISTRY OF TARTARIC ACIDS The following combinations are thus possible: 251 But Nos. 3 and 4 must be identical, as the radicals attached to the 2 asymmetric carbon atoms are identical. These spatial relationships may be represented: where a = H, b = OH, and c = C0 2 H. Note. At first sight it appears as though the radicals a, b, c in the lower half of fig. 1 were arranged in the and not the -f- order, as indicated. It must be remembered, however, that each part of the molecule must be looked at from the same point of view; and if we take the order of the radicals in the upper tetrahedron when arranged so that the solid angle which represents the point of attachment to the second tetra- hedron is pointed down, then we must regard the second tetrahedron from the same point of view, i.e. we must turn the figure upside down. It is then seen that the arrangement in the lower half of the molecule is the -f . Instead of using the above cumbrous figures, it is usual to regard such models as projected upon a plane surface, and to use the projections thus obtained (E. Fischer, B. 1891, 24, 2684): a C-b u C a \y )_C a b C a Jw a U b i e I b C-a I e 252 X. DIBASIC ACID8 or c c a-Lb b-fa b-U b-U a-Lb b-L-a Note. The manner in which these projection formulae are obtained can be best seen by means of models. A comparison of the three configurations at once shows that Nos. I and II are perfectly asymmetric, and are related to one another as object to mirror image; they should therefore represent the two optically active tartaric acids, and the compound of the two should represent the molecule of racemic acid. No. Ill has a plane of symmetry, and should therefore represent the non-resolvable, inactive acid meso-tartaric acid. The question as to whether No. I represents d- or /-tartaric acid has been settled by Fischer (B. 1896, 29, 1377) in favour of the d-acid. We thus have : CO 2 H CO 2 H CO 2 H H-[-OH OH-Ln OH-j-H OH-j-H H-K)H OH-f-H C0 2 H C0 2 H C0 2 H d I meso 1. Dextro-tartaric acid, acidum tarlaricum, is the tartaric acid found in nature. It was discovered by Scheele in 1769. It occurs in the free state, but chiefly as acid potassium salt, in various fruits, especially in the juice of grapes, from which potassic hydric tartrate (cremor tartari) separates in crystals during fermentation. When this is boiled with chalk and chloride of calcium it is transformed into the neutral calcium salt, from which the acid is liberated on addition of H 2 S0 4 . It crystallizes from water in large transparent monoclinic prisms, of a strong and purely acid taste, is readily soluble in water, also in alcohol, but almost insoluble in ether. It melts at 170, and its aqueous solution reduces an ammomacal silver solution upon warming. When melted, it is changed into an amorphous modification, and then into an anhydride, and when heated more strongly it carbonizes with the dissemination of a characteristic odour and formation of pyro-racemic and pyro- tartaric acids. Oxidation converts it either into dihydroxy- tartaric (p. 260) or tartronic acid, and then into formic and carbonic acids, &c. It is employed in medicine, dyeing, &c. TARTARIC ACID DERIVATIVES 253 Normal potassic tartrate, C 4 H 4 6 K + JH 2 O, forms mono- clinic prisms easily soluble in water. "Acid potassic tartrate, tartar, or cremor tartari, C 4 H 5 6 K, small rhombic crystals of acid taste, sparingly soluble in water, is much used in dyeing, medicine, &c. Potassic sodic tartrate, Rochelle or seignette salt, C 4 H 4 6 KNa + 4H 2 (1672), forms magnificent rhombic prisms. Calcic tartrate, C 4 H 4 6 Ca -f 4H 9 0, is a powder insoluble in water, but soluble in cold caustic-soda solution; on warming the solution it separates as a jelly, which redissolves upon cooling. Potassic antimonyl-tartrate, tartar emetic, C 4 H 4 6 (SbO)'K + JH 2 (see B. 15, 1540), is obtained by heating cream of tartar (cremor tartari) with anti- mony oxide and water. It crystallizes in rhombic efflorescent octahedra, readily soluble in water. It is poisonous and acts as an emetic, and is used as a mordant in dyeing. Fehling's solution is a solution of cupric sulphate mixed with alkali and Eochelle salt, and is largely used as an oxidizing agent. Thus with various carbon compounds, such as formal- dehyde, glucose, fructose, &c., it readily yields a precipitate of cuprous oxide. The diethyl ester is a thick oil, while the monoethyl ester crystallizes in prisms. Aceto-tartaric acid and amides of tartaric acid are known, and also various anhydrides. As an alcohol, it forms with nitric acid a dinitric ester, the so-called nitro-tartaric acid, C 2 H 2 (O N0 2 ) 2 (C0 2 H) 2 , which is readily hydrolysed, yielding dihydroxy-tartaric or tartronic acid. 2. Laevo-tartaric acid is identical in its chemical and also in almost all its physical properties with ordinary tartaric acid, but differs from it in that its solutions turn the plane of polar- ization of light to the left, in a degree equal to that in which the other turns it to the right. The crystallized salts show hemihedral faces like the salts of dextro-tartaric acid, but oppositely situated (see p. 254). When equal quantities of both acids are mixed together in aqueous solution, the solu- tion becomes warm, and we obtain: 3. Eacemic acid, (C 4 H 6 6 ) 2 , 2H 2 0, the composition of which was first established by Berzelius, who recognized it as being different from tartaric acid, and who developed the idea of isomerism from this first example in 1829. Racemic acid is obtained from tartar mother liquor. It differs from dextro tartaric acid in that its crystals are rhombic and efflorescent, and also less soluble in water than the former; further, the free acid is capable of precipitating a solution of calcium chloride 254 X DIBASIC ACIDS and is optically inactive (see below). The salts, which are termed racemates, and also the esters (B. 21, 518), show small differences from the tartrates in the proportions of their water of crystallization, in solubility, and melting-point or boiling- point. Molecular- weight determinations of dilute aqueous solutions of racemic acid indicate that under these conditions it is completely resolved into d- and Z-tartaric acids. 4. Meso-tartaric acid, a fourth tartaric acid, is inactive like the foregoing, but non-resolvable into the active acids. When heated with water at 170 it is partially transformed into racemic acid, which can then be resolved. It differs from racemic acid and also from the active acids in all its physical properties. It crystallizes in efflorescent rectangular plates, m.-pt. 143. The acid-potassium salt is readily soluble in water. Racemic Compounds. Resolution of Racemic Compounds into their Optically Active Components. Racemic acid has been re- solved by three distinct methods, all due to Pasteur; and as they are also applicable to the resolution of other racemic compounds, they are given below. 1. When a solution of sodium-ammonium racemate, Na(NH 4 )C 4 H 4 6 , 2H 2 O, is evaporated, beautiful rhombic crystals having the compo- sition NaNH 4 C 4 H 4 O 6 , 4H 2 and showing hemihedral faces* * Hemihedral Faces. These are small faces which are not perfectly symmetrically situated with respect to the other crystalline faces; they occur in only half the positions where they might be expected, and thus give the crystals a non-symmetric structure. The following figs, represent crystals of the d- and Z-sodic ammonic tartrates : The faces a and b are the hemihedral faces, and it will be noticed that the two crystals are non-superposable, but stand in the relationship of object to mirror-image. RESOLUTION OF RACEMIC COMPOUNDS 255 are obtained. Pasteur observed that these faces were not always similarly situated, but that certain crystals were dextro-hemihedral, while others were Isevo-hemihedral, so that one crystal formed the reflected image of the other. The Isevo-hemihedral crystals when dissolved exhibit dextro- rotation, and vice versa. If now the two kinds of crystals be separated from one another mechanically, and the free acid liberated from each, this will be found to consist, not of racemic acid, but in the one case of dextro- and in the other of Isevo- tartaric acid. In the process of crystallization it is essential that the tem- perature should be below 27, as otherwise, in place of the enantiomorphously related crystals of sodic-ammonic d- and /-tartrates, it is found that the crystals are all alike, possess no hemihedral faces, and consist of sodic-ammonic racemate. This temperature is termed the transition point, and for each racemic compound there is a definite transition temperature. Thus for sodic-potassic racemate it is 3, for rubidic racemate 40 '4, for ammonic-hydric malate 74. In the case of sodic-ammonic racemate the transition tem- perature may be determined by means of a dilatometer (Varit Hoff and Deventer, Zeit. Phys., 1887, 1, 173). This is a large thermometer, the bulb of which is filled with an equimolecular mixture of the two active salts and covered with oil, the level of which can be read off on the stem. As the temperature of the dilatometer is raised gradually, a considerable increase in volume is noticed at 27, due to the change expressed by the equation : NaNH 4 C 4 H 4 6 , 4H 2 O + NaNH 4 C 4 H 4 6 , 4 H 2 O = (NaNH 4 C 4 H 4 6 ) 2 , 2H 2 O + 6H 2 O. Other racemic compounds have been resolved by this simple method of crystallization. In all cases the temperature em- ployed must be below the transition temperature of the given substance, i.e. below the temperature at which the mixture of active components becomes transformed into the racemic compound. In this method of resolution no differences in solubility of the two components are met with, and hence no process of fractional crystallization can be employed; the two salts are deposited side by side, and must be picked out indi- vidually. The resolution of zinc ammonic lactate has already been mentioned (p. 215); further examples are sodic-potassic racemate, asparagin, and camphoric acid. 256 X. DIBASIC ACIDS 2. A very common method of resolving racemic acids is by combination with an optically active base, e.g. an alkaloid. In the case of racemic acid itself, Pasteur used /-cinchonine. The two salts formed are (a) d-acid -f- /-base, (b) /-acid + /-base. As these two salts are not enantiomorphously related, i.e. their molecules do not stand in the relationship of object to mirror-image, they possess different solubilities, and may be separated by fractional crystallization. The following is a list of some simple racemic compounds which have been resolved by this method; the salt named is the less soluble of the two, and crystallizes first. Acids. Quinine: d-tartrate. Strychnine: /-lactate, d-methyl- succinate, ^-methoxy-succinate, c/-phenyldibromo-propionate. Cinchonine: /-tartrate, d^-malate, d-mandelate. Brucine: d-tar- trate, /-valerate, /-aspartate. Racemic bases may be resolved by a similar process, viz. by combination with an optically active acid, e.g. d-tartaric, or even better, d-bromocamphor-sulphonic acid, and separating the two salts thus obtained by fractional crystallization. Thus ethyl-piperidine and coniine have been resolved by Ladenburg by using d-tartaric acid (A. 1888, 247, 85; cf. also Pope and Harvey on resolution of tetrahydro-/3-naphthylamine, J. C. S. 1901, 74; also Pope and Peachey, ibid. 1899, 1066 and 1105). 3. The third method consists in subjecting a solution of an ammonium salt of the acid to the action of some of the lower plant organisms, e.g. moulds, bacteria, yeasts, &c. Different organisms are required in different cases. Pasteur found that ordinary green mould Penicillium glaucum when grown in a solution of ammonium racemate, destroys the salt of the c?-acid and leaves a solution of the salt of the ^acid. If, however, the decomposition is allowed to proceed, the /-salt is also destroyed ; the reaction is a preferential decomposition, and, if stopped at a suitable time, practically all d-salt will have disappeared. It is obvious that in this method one of the active components is lost; but by using two distinct organisms in separate solutions it is sometimes possible to obtain both d- and /-compounds. Thus Penicillium glaucum grown in a solution of a salt of d-l- mandelic acid leaves the d-salt, and Saccharomyces ellipsoideus leaves the /-salt. Among other resolutions which have been effected by this method may be mentioned the destruction of /-lactic, /-mandelic, d-glyceric, /-ethoxy-succinic acids, and of d-methylpropyl-car- binol by Penicillium glaucum, and the destruction of d-mandelic, RACEMIG COMPOUNDS 257 ?-phenyldibromo-propionic acids and of ^-glucose, d-fmctose, and ^-manno.se by yeast (different species). 4. Markwald and M'Kenzie (B. 1901, 34, 469) have suggested another method of resolution, viz. by esterifying the racemic acid with an optically active alcohol. They used r-mandelic acid and Z-menthol, and found that the ^-component of the racemic acid was esterified somewhat more rapidly than the /. (Of. also Mackenzie, J. C. S. 1904, 378.) 5. Ostromisslensky (B. 1908, 41, 3035) has shown that a mix- ture of d- and /-isomerides can be easily separated if a super- saturated solution of the mixture is impregnated with a crystal of a suitable active material, thus a crystal of /-asparagine (p. 248) immediately produces the deposition of d-sodium am- monium tartrate from a supersaturated solution containing the d- and /-salts. A crystal of any optically active tartrate or of any isomorphous substance will also cause a separation of one of the active sodium ammonium tartrates, the actual salt de- posited depending on the activity of the crystal used, e.g. c?-sodium tartrate always deposits c?-sodium ammonium tar- trate. It is not necessary that the impregnating substance should be optically active; it must, however, be isomorphous or isodimorphous. Thus a crystal of glycine can cause the deposition of Z-asparagine from a supersaturated solution of d-l asparagine. This method of resolution cannot be used when the super- saturated solution contains a definite racemic compound of the d-l isomerides, and can thus be used as a method for deter- mining whether the given substance exists in solution as a d-l conglomerate or as a true racemic compound. Racemisation. When d-tartaric acid is heated with a small amount of water at 175 racemic acid is formed, together with a small amount of the meso acid. This conversion of an optically active compound into its racemic isomeride is usually termed racemisation, and is to be attributed to the transforma- tion of 50 per cent of the original active acid into its optical isomer. As further examples of racemisation, may be men- tioned the heating of d- valeric acid with concentrated sul- phuric acid and of amyl alcohol with sodium hydroxide. When valeric acid is boiled for eighty hours partial racemi- sation occurs, as is indicated by a slight diminution in its rotatory power. Racemisation often occurs during a chemical reaction; thus Z-mandelic acid, C 6 H 5 -CH(OH).C0 2 H, and hydrobromic acid at 50 yield not /-phenylbromo-acetic but (B480) $ 258 X. DIBASIC ACIDS r-phenylbromo-acetic acid. (Cf. also Easterfield, J. C. S. 1891, 72; Pope, ibid. 1901, 81, and P. 1900, 116.) Occasionally the racemisation occurs at the ordinary tem- perature, and is then termed autoracemisation; thus d-phenyl- bromo-acetic acid when kept in benzene solution for some three years becomes quite inactive, and ethyl d-bromo-suc- cinate in the course of four years diminishes in rotatory power from +40-96 to +9 (Walden, B. 1898, 31, 1416). Criteria for Determining the Nature of the Racemic Compound. The racemic substance may be one of the following: (a) A definite compound of 1 molecule of the ^-component with 1 of the I. (b) An ordinary mixture of the two in molecular pro- portions, (c) Mixed crystals, i.e. a solid solution of the two isomorphous antipodes without chemical combination. The first are termed racemic compounds proper, the second inactive conglomerates, and the third pseudoracemic compounds (Kip- ping and Pope, J. C. S. 1897, 989). A true racemic compound cannot be recognized by mole- cular-weight determinations, as in the gaseous form or in solution it is usually resolved into its components. In certain cases the recognition of the substance as a racemic compound is simple, e.g. sodic-ammonic racemate, which crystallizes in a different crystallographic system, and contains a different amount of water of crystallization from the active isomers, and possesses a definite transition point. When such simple criteria are of no use, Backhuis Eoozeboom (Zeit. Phys. 1899, 28, 494) recommends a study of the melting-point curves. These are obtained by taking the melting-points of mixtures of the compounds in different proportions, and then plotting the melting-points against the composition. The following types of curves are met with: Conglomerates, fig. 1. Racemic compounds, figs. 2 and 3. Mixed crystals, figs. 4, 5, and 6. B POLYHYDROXY DIBASIC ACIDS C B B 259 A represents the melting-point of the pure ^-compound, B that of the pure I, and C that of the racemic compound or mixture. These curves should be studied by aid of the Phase rule. E. Polyhydroxy Dibasic Acids Trihydroxy - glutaric acid, C0 2 H CH(OH) CH(OH) CH(OH) C0 2 H, and the stereo -isomeric acids saccharic, mucic, and isosaccharic acid C0 2 H CH(OH) CH(OH) CH(OH).CH(OH).C0 2 H, are the best-known examples. Many of these acids form lactones (p. 217), the so-called lactonic acids, and some of them also double lactones (cf. Fittig, A. 255, 1, et seq.). Trihydroxy-glutaric acid, C0 2 H.(CH.OH) 3 .C0 2 H, is a fre- quent oxidation-product of sugar varieties, e.g. of xylose and arabinose. According to theory, four stereo-isomers should exist, and four are actually known; they may be represented by the following projection formulae, where X = C0 2 H: ^\. OH4-H H-j-OH H-j-OH X H-^OH HO4-H HO-j-H X H-OH H-hOH HOHE H-K)H X Nos. 1 and 2 are enantiomorphously related and optically active, and can form a racemic compound. Compounds 3 and 4 are inactive substances of the type of mesotartaric acid. Saccharic acid is produced by the oxidation of cane-sugar, glucose, gulose, gulonic acid, mannitol, or starch by nitric acid, and exists in the d-, Z-, and r-forms (see Glucoses); (/-sac- charic acid when reduced yields glycuronic acid (see p. 222). All the three varieties are deliquescent. Mucic acid is formed by oxidizing dulcitol, the gums, muci- 260 X. DIBASIC ACIDS lages, and milk-sugar. It is a sparingly soluble, colourless, crystalline powder. The molecule being symmetrical in struc- ture, it is optically inactive. It is easily converted into deri- vatives of furane (see this). Isosaccharic acid is obtained by the oxidation of glucos- amine, C 6 H n 6 (NH 2 ). Theoretically, ten stereo -isomeric acids of the formula C0 2 H-[CH.OH] 4 .CO 2 H are possible, most of which (e.g. el- and i-manno-saccharic acids, talomucic acid, &c.) have been prepared by E. Fischer (B. 24, 539, 2137, 3622). For their relations to the hexoses, see the table appended to these. F. Dibasic Ketonic Acids Dibasic ketonic acids unite in themselves the properties of a ketone and of a dibasic acid. The following are known : 1. Mesoxalic acid, CO(C0 2 H) 2 or C(OH) 2 (C0 2 H) 2 (see p. 199), is prepared from dibromo-malonic acid, CBr 2 (C0 2 H) 2 , and baryta water or oxide of silver, thus: CBr 2 (C0 2 H) 2 + H 2 = CO(CO 2 H) 2 + 2HBr; also by boiling alloxan (p. 288) with baryta water. It crys- tallizes in deliquescent prisms (-f ILO). As a ketone it combines with NaHS0 3 , reacts with hy- droxylamine, and is reduced by nascent hydrogen to tar- tronic acid: O) 2 H.CO.CO 2 H + 2H = CO 2 H.CH(OH).CO 2 H. Since the acid and its salts still retain a molecule of water at temperatures above 100, this may be united in much the same manner as the water in chloral hydrate, corresponding with the formula C(OH) 2 (C0 2 H) 2 , " dihydroxy-malonic acid ". In fact, two modifications of the ethyl ester are known, viz. C(OH) 2 (C0 2 C 2 H 5 ) 2 and CO(C0 2 C 2 H 5 ) 2 . 2. Oxal-acetic acid, Butanone diacid, C0 2 H CH 2 CO C0 2 H, is an acid corresponding in many respects with aceto-acetic acid. Its ethyl ester is prepared by the action of sodium ethoxide upon a mixture of ethyl oxalate and acetate (p. 224), and also by the action of concentrated sulphuric acid upon ethyl acetylene-dicarboxylate. It is a colourless oil, but the alco- holic solution gives an intense dark-red coloration with ferric chloride. It is of importance as a synthetical reagent, as the hydrogen atoms of the methylene group can be replaced by POLYBASIC ACIDS 261 Sodium, and hence by various alkyl and acyl radicals (W. fPislicenus). 3. Acetone -dicarboxylic acid, Pentanone diatid, CO(CH 2 C0 2 H) 2 , obtained by treating citric acid with concentrated H 2 S0 4 , readily decomposes into acetone and 2C0 2 (see A. 261, 151). 4. Dihydroxy-tartaric acid, C0 2 H . CO - CO C0 2 H, or pro- bably C0 2 H.C(OH) 2 .C(OH) 2 .C0 2 H, is formed from pyro- catechol and nitrous acid, and by the gradual decomposition of nitro-tartaric acid. It melts at 98. The characteristic sparingly soluble sodium salt decomposes readily into carbon dioxide and sodium tartronate. CH 8 .CO.CH.CO,H 5. Diaceto-succmic acid, ^^^^^ (see p. 229). The ester of this is closely related to acetonyl-acetone, the latter being readily obtainable from the former by the action of caustic-soda solution ("Ketonic decomposition": cf. B. 33, 1219). 6. Diacetoglutaric acid, (X) 2 H . CHAc CH 2 CHAc CO S H. The ester of this acid is formed by condensing ethyl aceto- acetate with formaldehyde in the presence of diethyl amine, and is readily converted into derivatives of tetrahydrobenzenf or pyridine (Knoewnagel, A. 281, 94; cf. also B. 31, 1388). Most of these ketonic acids exhibit keto-enolic tantomerism, thus 5 isomerodes of diacetyl-succinic acid are known (Knorr, A. 1899, 306, 332). XL POLYBASIC ACIDS The polybasic acids contain two or more carboxylic groups in the molecule. The tribasic acids, like phosphoric acid, can give rise to three series of salts normal, monoacid, and di- acid. Both saturated and unsaturated acids are known, and also substituted derivatives. A. Saturated and Unsaturated Polybasic Acids A simple tribasic acid is tricarballylic acid, symmetrical pro- pane -tricarboxylic acid, C0 2 H.CH 2 .CH(C0 2 H).CH 2 .C0 2 H. It occurs in unripe beet, and is prepared (a) by the addition of hydrogen to aconitic acid, (b) by heating citric acid with hydriodic acid, and (c) synthetically from glycerol by trans- forming it into the tribromhydrin, C 8 H 6 Br 8 , treating this with 262 XL POLYBASIC ACH>S KCN, and hydrolysing the cyanide formed, C 3 H 5 (CN) 3 . Since the three hydroxyls in glycerol are distributed among three carbon atoms, the same holds good for the carboxyls in the acid, which has, therefore, the symmetrical constitution: C0 2 H CH 2 CH(C0 2 H) . CH 2 . CO 2 H. This acid is of importance in determining the constitution of citric acid, from which, as already seen, it can be- obtained by reduction with HI. It crystallizes in rhombic prisms, is readily soluble in water, and melts at 166. An unsaturated tribasic acid closely related to tricarballylic acid is aconitic acid, C0 2 H.CH:C(C0 2 H).CH 2 .C0 2 H, which contains two atoms of hydrogen less than tricarballylic acid. It is found in nature, in Aconitum Napellus, shave-grass, sugar- cane, beet-root, &c., and is prepared by heating citric acid, C 6 H 8 7 , when the elements of water are eliminated. It is a strong acid, crystallizable, readily soluble in water, melts at 191, and is reduced by nascent hydrogen to tricarballylic acid, hence its constitution. B. Hydroxy Polybasic Acids Citric acid, acidum citricum, hydroxy-tricarballylic acid, C0 2 H CH 2 .C(OH)(C0 2 H).CH 2 .CO 2 H (Sdieele, 1784; recognized as tribasic by Liebig in 1838), occurs in the free state in lemons, oranges, and red bilberries, and mixed with malic acid in gooseberries, &c., also as calcium salt in woad, potatoes, beet- root, &c. It is usually prepared from the juice of lemons by means of the lime salt. It crystallizes in large rhombic prisms ( + H 2 0), is readily soluble in water, moderately in alcohol, but only sparingly in ether. It loses its water of crystal- lization at 130, melts at 153, and breaks up at a higher temperature first into aconitic acid and water, and then into carbon dioxide, itaconic acid, citraconic anhydride, and acetone. Oxidizing agents effect a verv thorough decomposition. Calcium citrate is precipitated as a white sandy powder when a mixture of calcium chloride and alkali citrate solutions is boiled. The three series of salts are well characterized; the alkali salts are soluble in water, the others mostly insoluble. Among the derivatives may be mentioned mono-, di-, and' tri ethyl citrates and triethyl aceto-citrate, CO 2 Et GH, 0(0 - CO CHaXCOgEt) CH S . CO a Et. CYANOGEN COMPOUNDS 263 The formation of this last is a direct proof of the alcoholic character of citric acid. The amides of citric acid are con- verted by concentrated H 2 S0 4 into citrazinic acid, C 6 H 5 N0 4 , a pyridihe derivative (B. 17, 2681). The constitution of citric acid is arrived at (a) from its con- version into aconitic acid by the elimination of water, (b) from its reduction to tricarballylic acid, and (c) from its synthesis from 1 : 3 dichloroacetone, e.g. : CH 2 C1.CO.CH 2 C1 + HCN CH 2 C1.C(OH)(CN).CH 2 C1 CN.CH 2 .C(OH)(CN).CH 2 .CN CX) 2 H.CH 2 .C(OH)(C0 2 H).CH 2 .C0 2 H. The acid has been synthesised by Lawrence (J. C. S. 1897, 71, 457) by an application of Eeformatsky's reaction, i.e. the condensation of a halogen derivative with a ketone in the presence of zinc. The substances used were ethyl bromacetate, ethyl oxalacetate, and pure zinc turnings : _ CO 2 Et-CH 2 .C(OZnBr).CO 2 Et CH 2 .CO 2 Et. This condensation product reacts with water, yielding ethyl citrate, C0 2 Et.CH 2 .C(OH)(C0 2 Et).CH 2 .C0 2 Et, zinc oxide, and hydrogen bromide. Citric acid is also formed when solutions of glucose are fer- mented by certain moulds, e.g. Citromycetes pfefferianus and C. glaber (Wehner, Bull. Soc. Chim. 1893 [III], 9, 728). Acids containing more than three carboxylic groups do not, as a rule, occur in nature,^ but a number of esters of such acids have been prepared by means of the aceto-acetic ester and malonic ester syntheses. XII. CYANOGEN COMPOUNDS Under the name of the cyanogen compounds is included a group of substances which are derivable from cyanogen, C 2 N 2 . Cyanogen itself is a gas of excessively poisonous properties which behaves in many respects like a halogen; and its hydrogen compound, hydrocyanic acid, HCN, is an acid re- 264 XII. CYANOGEN COMPOUNDS sembhng hydrochloric acid to a certain extent. In many cyanogen compounds the monovalent group (CN) plays the part of an element; cyanogen is to be regarded as the isolated radical (CN), which, however, possesses the double formula C 2 N 2 , just as a molecule of chlorine (C1 2 ) is made up of two atoms. The cyanogen group is further capable of combining with the halogens, hydroxyl, sulphydril (SH), amidogen, &c. From the compounds so obtained numerous others are derived by the entrance of alkyl radicals in place of hydrogen. Such derivatives invariably exist in two isomeric forms, sharply distinguished from one another by their properties. They are often termed normal and iso compounds, and the isomerism is of very great interest. (See table, p. 265.) Polymeric modifications of most of those compounds also exist. The number of cyanogen compounds known is thus a very large one. Carbon and nitrogen do not combine directly except in the presence of an alkali, and then a metallic cyanide is formed. As examples of this reaction, we have the following: 1. When nitrogen is led over a red-hot mixture of coal and carbonate of potash, potassium cyanide, KCN, is formed, espe- cially under a high pressure. 2. Ammonium cyanide is formed when ammonia is passed over red-hot coal. 3. Potassium cyanide is formed when nitrogenous organic compounds such as leather, horn, claws, wool, blood, &c., are heated with potashes. 4. Hydrocyanic acid is formed when electric sparks are passed through a mixture of acetylene and nitrogen, and also by the action of the silent electric discharge on a mixture of cyanogen and hydrogen. It is also formed (commercial method) when a carefully dried mixture of hydrogen, am- monia, and a volatile carbon compound (CO, C0 2 , C 2 H 2 , &c.) is passed over heated platinized pumice. (For further modes of formation, see p. 266 et seq.) The original material for the preparation of most of the cyanogen compounds is potassium ferrocyahide, which is manu- factured on the large scale and possesses the great advantage over potassium cyanide of being stable in the air and compara- tively non-poisonous. I CYANOGEN COMPOUNDS SUMMARY OF THE CYANOGEN COMPOUNDS Relation to carbonic acid, &c. (&ee p. 279.) Name. Formula. Nitrile of oxalic acid, Cyanogen, N:C-C:N Nitrile of formic acid, Hydrocyanic acid, Alkyl derivatives: (a) Nitriles, (6) Isonitriles, NiC.H R.CiN R-N:C Cyanogen chloride, bromide, iodide, N-C-Cl CO 3 H 2 + NH 3 -2H 2 O, (Nitrile of carbonic acid, eventually Carbiinide), Cyanic acid, Alkyl derivatives: (a) Methyl cyanate, (6) isocyanate, N-C-OH N:C-O.CH 3 O:C:N.CH 3 Thiocyanic acid, Alkyl derivatives : (a) Ethyl thiocyanate (6) Allyl isothio- cyanate, N-C-SH N:C.S.C 2 H 5 S:C:NC 3 H 6 CO 3 H 2 -f 2NH 3 3H 2 O, (Nitrile and amide of car- bonic acid, eventually Carbo-di-imide, see p. 277), Cyanamide, Alkyl derivatives: (a) Alkyl cyana- mide, (6) Carbo-di-imide, N:C-NH 2 NiC-NH-K RN:C:NK* The amic acid of car- bonic acid, Carbamic acid, NH 2 .CO-OH The amide of carbonic acid, Urea, CO(NH 2 ) 2 Thio-urea, Alkyl derivatives : (a) Alkyl-thio-ureas, (6) Imido-thio-carba- mine compounds, CS(NH 2 ) 2 NH 2 .CS.NHR NH:< 2 CO 3 H 2 + 3NH 3 -3H 2 O, (Amidine), Guanidine, HNlCKNHj)., * R = alkvl radical. 266 XII. CYANOGEN COMPOUNDS A. Cyanogen and Hydrocyanic Acid Cyanogen, N-C-CjN, which was discovered by Gay-Lussac in 1815, occurs in the gases of blast-furnaces and in coal gas. As the nitrile of oxalic acid, it may be obtained by the abstraction of the elements of water from ammonium oxalate by means of P 4 10 ; also in the same way from the intermediate product of this reaction, oxamide : NH 4 0-CO.CO.ONH 4 -4H 9 O = N:C-C:N, NH 2 .CO.CO.NH 2 -2H 2 = N:C-C:N. It is usually prepared by heating dry silver cyanide, AgCN, or mercuric cyanide, Hg(CN) 2 , strongly : Hg(CN) 2 = Hg + C 2 N 2 ; or by heating a solution of cupric sulphate with potassium cyanide (B. 18, Kef. 321). Cyanogen is a colourless gas of a peculiar unpleasant odour resembling that of bitter almonds, and is terribly poisonous. It is easily liquefied and solidified (sp. gr. 1*8 of the liquid; m.-pt. 34; b.-pt. 21), is soluble in 0'25 vol. of water and in even less alcohol. The solutions become dark upon stand- ing, with separation of a brown powder ("Azulmic acid"), while oxalic acid, ammonia, formic acid, hydrocyanic acid, and urea are to be found in the liquid. The formation of the oxalic acid and ammonia is due to normal hydrolysis, and that of formic acid to the hydrolysis of the hydrocyanic acid formed as an intermediate product. In presence of a minute quantity of aldehyde, oxamide is formed as the result of the addition of water. Cyanogen combines with heated potassium to KCN, and dissolves in aqueous potash to form KCN and KCNO. Paracyanogen, (CN) X , is a polymer of cyanogen. It is an amorphous brown powder which is formed as a by-product when mercuric cyanide is heated; upon further heating, it is transformed into cyanogen. Hydrocyanic acid, pmssic acid, CNH, was discovered about the year 1782 by Scheele, and investigated closely by Gay- Lussac. Some of the more interesting methods of formation are the following : 1. It is readily liberated from its salts by the action of almost any other acid, even carbonic acid; and even complex HYDROCYANIC ACID 267 cyanides, e.g. potassium ferrocyanide, when distilled with moderately dilute sulphuric acid yield hydrogen cyanide: K 4 Fe(CN) 6 + 5H 2 S0 4 = 6HCN + FeSO 4 + 4KHSO 4 . The ferrous sulphate produced reacts with more ferrocyanide to form potassium ferrous ferrocyanide, FeK 2 (FeC 6 N 6 ), which is not affected by dilute acids (see p. 269); consequently only half of the cyanogen present is converted into hydrocyanic acid. When concentrated sulphuric acid is employed in place of the dilute, carbon monoxide and not hydrocyanic acid is obtained. 2. As the nitrile of formic acid, it may be prepared by the action of dehydrating agents on ammonium formate or form- amide : H.CO-ONH 4 = H.CO.NH 2 + H 2 O = HGN + 2H 2 O. 3. Together with oil of bitter almonds, C 6 H 5 .CHO, and grape-sugar, C 6 H 12 6 , by the hydrolysis of the glucoside amygdalin under the influence of the enzyme " emulsin " (see Benzaldehyde) : SH0 = The oil of bitter almonds and its aqueous solution (aqua amarum amygdalarum) prepared from the almonds them- selves consequently contain HCN. The acid occurs in the free state in the tree Pangium edule, found in Java, more particularly in the seeds. It exists in the form of glucosides in various plants (C. C. 1906, ii, 1849: 1909, i, 387). 4. By the action of ammonia and chloroform on alcoholic potash under pressure. Cf. p. 103. For other syntheses, see p. 264. Hydrogen cyanide is a colourless liquid boiling at 25 and solidifying at 12. Sp. gr. 0'70. It has a peculiar odour and produces an unpleasant irritation in the throat, is miscible with water, and burns with a violet flame. Like potassium cyanide, it is one of the most terrible of poisons. The best antidotes are stated to be hydrogen peroxide or small quantities of chlorine mixed with air. When absolutely pure it can be preserved unchanged, but it decomposes in presence of traces of water or ammonia, with separation of a brown mass and formation of ammonia, formic acid, oxalic acid, &c. The addition of minute quantities of mineral acids renders the aqueous solution more stable. 268 XII. CYANOGEN COMPOUNDS Liquid hydrocyanic acid is a good solvent for many salts, and has a high ionizing power. Acids (sulphuric and trichloro- acetic), however, do not appear to dissociate when dissolved in the liquid. The acid has many properties of an unsaturated compound. It is readily reduced by nascent hydrogen to methylamine. In the presence of hydrochloric acid it combines with water yielding formamide. With diazomethane (Chap. LI) it yields methyl cyanide together with methyl carbylamine. With hydrogen chloride it gives iminoformyl chloride, NHrCHCl, a compound of importance in the synthesis of aromatic alde- hydes (A. 1906, 347, 347); but has not been isolated. From ethyl acetate solution a product 2HCN, 3HC1 = NH:CH-NH- CHC1 2 , HC1, dichloromethyl formamidine hydrochloride is obtained. It combines directly with most aldehydes and ketones, yielding cyanhydrins (nitriles of hydroxy acids), (p. 206), and also with certain unsaturated compounds, espe- cially in the presence of potassium cyanide, yielding saturated nitriles (Lapworth, J. C. S. 1903, 995; 1904, 1214; Knoe- venagel, B. 1904, 37, 4065); e.g. a-phenylcinnamo-nitrile, CHPh:CPh.CN, yields diphenylsuccinylo-nitrile, CN-CHPh- CHPh-CN. Hydrocyanic acid is an extremely weak monobasic acid (K = 0*0013 x 10~ 6 ), and its salts are decomposed even by carbonic acid. It is a typical tautomeric compound. Its reduction to an amine and its hydrolysis to formic acid are similar to the corresponding reactions of methyl cyanide, and it might be urged that these reactions favour the nitrile for- mula HCjN Both reactions are, however, compatible with the view that it has the carbylamine structure H-N:C. The salts are usually regarded as carbylamine derivatives (see derivatives of divalent carbon, Chap. L, D), and it might be argued that the free acid has a similar structure. Such an argument is, however, unsound, as numerous examples are known where salts have a structure quite different from that of the acid from which they are prepared (cf. ethyl aceto- acetate and pseudo acids). Hydrocyanic acid can be detected by converting it either into Prussian blue or into ferric thiocyanate. In the former case the solution to be tested is treated with excess of caustic soda and some ferrous and ferric salt, boiled, and acidified, when Prussian blue results; in the latter the solution is evaporated to dryness together with a little yellow sulphide FERROCYANIDES AND FERRICYANIDES 269 of ammonium, the residue taken up with water and ferric chloride added, when the blood -red colour of ferric thio- cyanate is obtained. Trihydrocyanic acid, (CNH) X , results from the polymer- ization of hydrocyanic acid under certain specified conditions. It forms white, acute-angled crystals, which readily yield hy- drogen cyanide when heated above 180. Its molecular weight is still unknown. Cyanides. The cyanides of the alkali and alkali -earth metals are soluble in water, and the solutions have a strongly alkaline reaction due to the hydrolysing action of the water (cf. Soaps, p. 159). The salts of the heavy metals, with the exception of mercuric cyanide, are insoluble in water. Potassium cyanide, KCN, forms colourless deliquescent cubes, sparingly soluble in alcohol. The commercial product usually contains large amounts of potassium carbonate due to the action of atmospheric carbon dioxide. It is formed when potassium ferrocyanide is fused, and the product extracted with water: K 4 FeC 6 N 6 = 4KCN + FeC 2 + N 2 . Large quantities are manufactured by Beilby's process, which consists in treating a fused mass of potassium carbonate and carbon with ammonia, the product being a molten cyanide of high strength. The pure salt can be prepared by passing hydrogen cyanide into an alcoholic solution of potassium hydroxide. It reacts with hydrogen peroxide in two different ways (cf. Masscrn, J. C. S. 1907, 1449): 1. 80 % KCN -f H 2 O 2 KCNO + H 2 and KCNO + 2H 2 NH 3 + KOH + C0 2 ; 2. 20 % KCN + 2H 2 O > NH 3 + H-COOK. Mercuric cyanide, Hg(CN) 2 , crystallizes in colourless prisms, is stable in the air, readily soluble in water, and excessively poisonous. Its aqueous solution is a non-conductor of the electric current, and does not give the ordinary reactions for a mercuric salt or for a cyanide (cf. B. 1908, 41, 317). Argentic cyanide, AgCN, forms a white flocculent precipitate closely resembling argentic chloride in appearance, but is soluble in hot concentrated nitric acid. Complex Cyanides. The double cyanides, which are pro- duced by dissolving the insoluble metallic cyanides in a solu- tion of potassium cyanide, are divided into two classes. Th(j 270 XII. CYANOGEN COMPOUNDS members of the one class are decomposed again on the addition of dilute mineral acids, with separation of the insoluble cyanide and formation of hydrocyanic acid, e.g. KAg(CN) 2 ; K 2 Ni(CN) 4 . The members of the other class are much more stable, do not evolve hydrocyanic acid, and comport themselves as salts of particular acids; to this class belong potassium ferrocyanide, K 4 Fe(CN) 6 , [Fe(CN) 2 , 4KCN], and potassium ferricyanide, K 3 Fe(CN) 6 , [Fe(CN) 3 , 3KCN]. The members of this second class are often termed complex salts, and are the metallic salts of complex acids, e.g. hydroferrocyanic acid, H 4 FeC N 6 , and hydroferricyanic acid, H 3 FeC 6 N 6 , which are formed when the salts are decomposed with mineral acids. Certain salts of the latter acid are not decomposed at all by dilute acids, for in- stance Prussian blue, but they are by caustic potash (which converts Prussian blue into Fe(OH) 3 arid K 4 FeC 6 N 6 ). These complex salts, as a rule, do not give the reactions characteristic of simple cyanides, e.g. white precipitate with silver-nitrate solution, owing to the fact that in solution they do not yield the simple cyanide ions CN but the more complex anions FeC 6 N 6 and FeC 6 N 6 . Potassium ferrocyanide, yellow prussiate of potash, K 4 Fe(CN) 6 -f- 3H 2 0, may be obtained by adding excess of potassium cyanide to a solution of ferrous sulphate, or by dissolving iron in a solution of cyanide of potassium, when hydrogen is evolved, thus: 2KCN + Fe + 2H 2 O = Fe(CN) 2 + 2KOH -f H 2 ; Fe(CN) 2 -f 4KCN = K 4 Fe(CN) 6 . The old commercial method consisted in fusing together scrap-iron, nitrogenous organic matter, and crude potassic carbonate. It is now usually manufactured from the hydrogen cyanide present in crude coal gas or the gas from coke ovens. The spent oxide used in the purification of coal gas contains Prus- sian blue (ferric ferrocyanide, p. 271). The spent oxide is heated with hot milk of lime, and the Prussian blue thus transformed into calcium ferrocyanide, from which the potas- sium salt can be prepared. Another method consists in passing the coal gas, before it has been subjected to dry purification, through an alkaline solution containing an iron salt. The sulphuretted hydrogen reacts with the iron salt, forming ferrous sulphide, and this FORROCYANIDES AND FERRICYANIDES 271 with the hydrogen cyanide and alkali (potassium carbonate) yields potassium f errocyanide : FeS + 6HCN + 2K 2 CO 3 = K 4 FeC 6 N 6 + H 2 S + 2CO 2 + 2H 2 O. It forms large, lemon-coloured monoclinic plates, which are stable in the air and easily soluble in water, but insoluble in alcohol. Concentrated HC1 yields hydro-ferrocyanic acid, H 4 FeC 6 Ng, in the form of white needles. With a solution of CuS0 4 , a red-brown precipitate of cupric ferrocyanide, or Hatchetfs brown, CuJFeCgNg, is thrown down, and with solu- tions of ferrous and ferric salts the well-known characteristic precipitates (see below). Chlorine oxidizes it to Potassium ferricyanide, red prussiate of potash, K 3 FeC 6 N G , thus : 2K 4 FeC 6 N 6 + C1 2 = 2K 3 FeC 6 N 6 + 2KC1. This crystallizes in long, dark-red, monoclinic prisms which are readily soluble in water. The solution decomposes when kept, and acts as a strong oxidizing agent in the presence of alkali, potassium ferrocyanide being reproduced. Hydro-ferricyanic acid, H 3 FeC 6 N 6 , forms brown needles, and is easily decomposed FERRO- AND FERRI-CYANIDES OF IRON Ferrocyanides. Ferricyanides. Ferrous salts, Potassium-ferro-ferrocyanide, K 2 Fe(FeCgN 6 )*, fromFeS0 4 + KjFeCsNe; white, becom- ing rapidly blue in the air from conversion into TurribulVs blue, Fe 3 ii (FeC 6 N) 2 iil , from FeS0 4 (excess) + i Ferric salts, Potassium -ferri - ferrocyanide, KFe^FeCeNe), or soluble Prussian blue, which is also formed from ferrous sul- phate with an excess of potassic ferricyanide. (FeCls-t- K 3 FeC 6 Ngive no . precipitate, but only a brown color- ation.) Insoluble Prussian blue or Williamson's blue, Fe 4 iii (FeC 6 N 6 ) 3 iv , from FeCl 8 + K 4 FeC 6 N 6 ; blue powder with a copper glance. 272 XII. CYANOGEN COMPOUNDS The formation of Prussian blue was first observed by Diesbach about the year 1700. As regards the constitution of hydro-ferro- and hydro-ferri- cyanic acids, one may make the assumption that they contain the tervalent radical, (C 3 N 3 ) Ui , " tricyanogen ", of cyanuric acid (see p. 272): Potassium ferrocyanide Potassium ferricyanide. Turnbull's blue. When ferrocyanide of potassium is oxidized by nitric acid, nitro - prussic acid is formed, the sodium salt of which, -+- 2H 2 0, crystallizes in red prisms soluble in water. It forms a valuable reagent for the detection of sulphuretted hydrogen, an alkaline solution yielding with the latter a splendid but transient violet coloration. B. Halogen Compounds of Cyanogen Cyanogen chloride, C1N:0 (Berthollet), is a colourless con- densable gas of a most obnoxious pungent odour, is somewhat soluble in water, and boils at 15 -5. It is prepared by the action of chlorine upon mercuric cyanide or upon dilute aqueous hydrocyanic acid, CNH + C1 2 = CNC1 + HC1. It polymerizes readily to cyanuric chloride, and yields sodium chloride and cyanate with aqueous sodium hydroxide: CN.Cl + 2NaOH = CN-ONa + ClNa -f H 2 O. Cyanogen bromide, CNBr, forms transparent prisms, and is prepared by the action of sulphuric acid on a mixture of bromate, bromide, and cyanide of sodium: 5HBr-f 3HCN = SBrCN + 3HBr + 3H 2 O. Cyanogen iodide, ONI, forms beautiful white prisms, smelling intensely both of cyanogen and iodine, and subliming with the utmost ease. (For constitution cf. Chattaway and PFadmore, J. C. S. 1902, 191.) Cyanuric chloride, trichlorocyanogen, (CC1) 3 N 3 , is obtained from cyanogen chloride, or from hydrocyanic acid and chlor- ine in ethereal solution. It forms beautiful white crystals of a.n unpleasant pungent odour, melts at 145, and boils at CYANIC AND CYANURIC ACIDS 273 190. Boiling water decomposes it with formation of hydro- gen chloride and cyanuric acid C. Cyanic and Cyanurie Acids Cyanuric acid is formed when urea is heated, either alone or in a stream of chlorine gas; and when this acid is distilled, and the vapour condensed in a freezing-mixture, cyanic acid, CNOH, is obtained as a mobile liquid of a pungent odour: CaNsOaHg = 3 CNOH It is exceedingly unstable; when taken out of the freezing- mixture it changes, with explosive ebullition, into a white porcelain-like mass which consists of cyanuric acid 70 per cent, and cyamelide 30 per cent. Potassium cyanate, CNOK, fre- quently also termed potassium isocyanate, is prepared by the oxidation of an aqueous solution of potassium cyanide b" means of permanganate (A. 259, 377); or by fusing potassium cyanide or yellow prussiate of potash with Pb0 2 or Mn0 2 : (CNK + = CNOK). It crystallizes in white plates, readily soluble in water and alcohol. Ammonium cyanate, CNO (NH 4 ), forms a white crystalline mass, and is of especial interest on account of the readiness with which it changes into the isomeric urea, CO(NH 2 ) 2 (p. 281). When these salts are decomposed with mineral acids, free cyanic acid is not formed, but its products of hydrolysis, viz. carbon dioxide and ammonia : CONH + H 2 = C0 2 + NH 3 . This decomposition is avoided by the addition of dilute acetic acid (instead of hydrochloric), but in the latter case the cyanic acid changes into its polymer cyanuric acid, and the hydrogen- potassium salt of the latter slowly crystallizes out. When the hydrogen atom in the cyanic acid molecule is replaced by alkyl radicals, two distinct groups of compounds are possible. The derivatives which are constituted on the type N;CCKR are termed the normal, and those on the type 0:C:NR the iso-compounds. Ethyl isocyanate, cyanic ether, : C : N CH 2 CH 3 , obtained when potassium cyanate is distilled with ethyl iodide or potassium ethyl-sulphate, is a colourless liquid of suffocating odour, distilling at 60, and is decomposed by water. It does (B480) S 274 XIL CYANOGEN COMPOUNDS not behave as a typical ester, since when hydrolysed with acids or alkalis it yields ethylamine and carbon dioxide: Water, which acts in a similar manner, gives rise to the more complicated urea derivatives; ammonia and amines also produce derivatives of urea, and alcohol yields derivatives of carbamic acid (see Carbonic Acid Derivatives). The production of ethylamine as one of the products of hydrolysis is usually regarded as a strong argument in favour of the view that in the original isocyanate the ethyl group is attached to nitrogen and not to oxygen, e.g. 0:C:N-Et. It is questionable, however, whether free cyanic acid and cyanate of potassium possess analogous constitutions, since frequent observations have shown that the normal cyanic compounds readily change into the iso- (see below) ; theoretical considerations indeed make it more probable that cyanic acid has the constitution N|COH, according to which it appears as the normal acid, with cyanogen chloride as its chloride. Normal cyanic esters are not known (cf. A. 287, 310). Cyanuric acid, C 3 N 3 3 H 3 , = (CN) 3 (OH) 3 (Scheele), obtained by heating urea, or by the action of water on cyanuric chloride, forms transparent prisms containing two molecules of water of crystallization. It effloresces in the air, and dissolves readily in hot water. It is a tribasic acid. The sodium salt is spar- ingly soluble in cone. NaOH; the (Cu-NH 4 ) salt possesses a characteristic beautiful violet colour. Upon prolonged boiling with hydrochloric acid it is hydrolysed to C0 2 and NH 3 , while phosphorus pentachloride converts it into cyanuric chloride. Only one cyanuric acid is known, and owing to the fact that the N-methyl derivative is obtained by the action of diazo-methane is represented by the iso-structure : (Compare also Hantzsch, B. 1906, 39, 139). Cyanuric acid is a pseudo acid, as its salts and also chloride have the normal structure. The mercuric salt exists in two isomeric forms. Two distinct groups of alkyl derivatives are, however, known normal cyanuric esters, e.g. ethyl cyanurate, ISO-THIOCYANATES 275 which is formed by the action of ethyl iodide on silver cyanu- rate at the ordinary temperature, or by the action of sodium ethoxide on cyanogen chloride or cyanuric chloride, is readily changed into an isocyanuric ester, e.g. ethyl isocyanurate, These isocyanurates are often formed instead of the normal compounds if the temperature is not kept low, e.g. when a cyanurate is heated with potassium ethyl-sulphate. They are further formed by the polymerization of the isocyanic esters, oeing thus obtained as by-products in the preparation of the latter. The constitution of the normal compounds is largely based on the fact that on hydrolysis they behave as normal esters and yield ethyl alcohol and cyanuric acid. The isocyanurates, on the other hand, usually yield primary amines, e.g. ethyl- amine, and hence presumably the alkyl group is attached to nitrogen in the isocyanurate molecule. For mixed normal iso-esters, see Hantzsch and Bauer, B. 1905, 38, 1005. D. Thioeyanic Acid and its Derivatives Nearly every oxygen derivative of cyanogen has a sulphu r analogue. As examples, we have the salts of thiocyamc acid. Potassium thiocyanate, -sulphocyanate, -sulphocyanide, -rhod- anide, CNSK, is readily formed when potassium cyanide is fused with sulphur, or when an aqueous solution of KCN is evaporated with yellow ammonium sulphide. It is usually prepared by fusing potassium ferrocyanide with sulphur and potashes. It forms long colourless deliquescent prisms, extremely soluble in water with absorption of much heat, and also readily soluble in hot alcohol. Ammonium thiocyanate, CNS(NH 4 ), is formed when a mixture of carbon disulphide, concentrated ammonia, and alcohol (Millori) is heated, dithiocarbamate and trithiocarbonate of ammonia being formed as intermediate products: = CNSH + H 2 S. It forms colourless deliquescent plates, readily soluble in alcohol, and when heated to 130-140 is partially transformed 276 XII. CYANOGEN COMPOUNDS into the isomeric thio-urea, just as ammonium cyanate is into urea. It precipitates silver thiocyanate, CNSAg (white), from solutions of silver salts, and is therefore employed in the titration of silver, with ferric sulphate as indicator; and it gives with ferric salts a dark blood -red coloration of am- monium ferrithiocyanate, 2Fe(CNS) 8 , 9NH 4 CNS, 4H 2 0. This last reaction is exceedingly delicate. Mercurous thio- cyanate, HgCNS, is a white powder insoluble in water, which increases enormously in volume upon being burnt (Pharaoh's serpents). The free thiocyanic acid, CNSH, as obtained by decomposing the mercurous salt with hydrochloric acid, is a pale-yellow liquid of pungent odour, but when pure is a colourless solid, m.-pt. 5. The acid and its salts appear to have the normal structure HS'C|N. At the ordinary tem- perature it polymerizes to a yellow amorphous substance, and decomposes in concentrated aqueous solution, with formation of persulphocyanic acid, C 2 N 2 S 3 H 2 (yellow crystals). Concentrated sulphuric acid decomposes the thiocyanates with formation of carbon oxy - sulphide : CNSH + H 2 = COS-f NH 3 ; sulphuretted hydrogen decomposes them into carbon disulphide and ammonia : CNSH + H 2 S = CS 2 + NH 3 . The alkyl derivatives of thiocyanic acid exist in two distinct forms, corresponding with the normal and iso-cyanates. Normal Thiocyanates. Ethyl thiocyanate, N:C-S.CH 2 . CH 3 , is obtained either (1) by the distillation of potassium ethyl -sulphate with potassium thiocyanate, or (2) by the action of cyanogen chloride upon ethyl mercaptide. It is a colourless liquid with a peculiar pungent odour of leeks, boils at 142, and is almost insoluble in water. Alcoholic potash hydrolyses it in the normal manner, yielding ethyl alcohol and potassium thiocyanate; in other reactions, however, the alkyl radical remains united to sulphur; thus nascent hydro- gen reduces it to mercaptan, and fuming nitric acid oxidizes it to ethyl-sulphonic acid. These reactions, combined with its formation from a mer- captide, indicate that the ethyl group is directly attached to sulphur, viz. C 2 H 5 -S-C:N. Allyl thiocyanate, NjCSC 3 H 5 , is a colourless liquid smell- ing of leeks. It boils at 161, and when distilled is converted into the isomeric mustard oil. The iso-thiocyanates are usually known as mustard oils, and are more stable than the normal thiocyanates. They contain the alkyl radical attached to nitrogen, and not to CYANAMIDE AND ITS DERIVATIVES 277 sulphur (cf. Isocyanates), since on hydrolysis they yield primary amines, e.g. : S:C:NEt + 2H 2 = H 2 S + C0 2 + NH 2 Et, and also on reduction: S:C:NEt-f 4H = NH 2 Et + CH 2 S. The thiomethylene formed in this last reaction immediately polymerizes to (CH 2 S) 3 . The commonest iso-thiocyanate is allyl mustard oil, commonly known as mustard oil, since the odour and taste of mustard seeds (Sinapis niger) are due to this compound. It does not exist as such in the seeds, but is formed from a glucoside, potassium myronate, when the seeds are pulverized and left in contact with water. The reaction is a process of fermentation, and is due to the presence of an enzyme, myrosin, in the seeds: C 10 H 18 10 NS 2 K = C 6 H 12 O fl + KHS0 4 + SCNC 3 H 6 . It is a liquid sparingly soluble in water and of exceedingly pungent odour, which produces blisters on the skin, and boils at 151. It is also obtained by distilling allyl thiocyanate, owing to a molecular rearrangement, or by the action of carbon disulphide upon allylamine: CS 2 + NH 2 .C 3 H 6 = CS:N.C 3 H 6 + H 2 S. This reaction proceeds in two stages, a dithiocarbamate, C 3 H 5 NH.CS.SNH 3 C 3 H 5 , the allylamine salt of allyl-dithio- carbamic acid being first formed, and this is changed into allyl iso-thiocyanate when distilled with mercuric chloride. (See Dithiocarbamic acid, p. 296.) Ethyl iso-thiocyanate, C 2 H 5 N:CS (b.-pt. 134), and methyl iso-thiocyanate, CH 3 N:CS (solid, m.-pt. 34, b.-pt. 119), &c., closely resemble the allyl compound, and are obtained in an analogous manner by the action of carbon disulphide upon ethylamine, methylamine, &c. The mustard oils are also obtained by distilling alkylated thio-ureas (p. 297) with syrupy phosphoric acid (Hofmann, B. 15, 985), or with concentrated hydrochloric acid. E. Cyanamide and its Derivatives The Amide of Cyanic Acid. Cyanamide, N;C.NH 2 , is formed by leading cyanogen chloride into an ethereal solution 278 XII. CYANOGEN COMPOUNDS of ammonia, CNC1 + 2NH 8 = CN-NH 2 + NH 4 C1, or by the action of HgO upon thio-urea in aqueous solution ("de- sulphurization"), NH 2 .CS-NH 2 - NC-NH^ + H 2 S. It is a colourless crystalline hygroscopic mass, readily soluble in water, alcohol, and ether. It melts at 40, and when heated to 150 changes into the polymeric dicyan-diamide with explosive ebullition; the same change occurs on evaporat- ing its solution or allowing it to stand. Dilute acids cause it to take up the elements of water, with formation of urea : N:C-NH NH 2 ; and it combines in an analogous manner with hydrogen sul- phide to thio-urea. When heated with ammonium salts, it yields salts of guanidine. Cyanamide behaves as a weak base, forming crystalline, easily decomposable salts with acids and, at the same time, as a weak acid, yielding a sodium salt, CNNHNa, a lead and a silver salt, &c. The last is a yellow powder, and has the composition CN 2 Ag 2 . The calcium derivative of cyanamide, N;CNOa, is manu- factured for use as a fertilizer, as, in the soil, the nitrogen be- comes available for the plant in the form of ammonia. It is manufactured by passing air or nitrogen over calcium carbide at about 800-1000, CaC 2 + N 2 = CaCN 2 + C, or by passing nitrogen over a mixture of lime and carbon heated to 2000. An excess of carbon is used, and the crude product, which forms a black powder, contains 14-23 per cent of nitrogen (cf. Abs. 1904, i. 562). The presence of a small amount of calcium chloride accelerates the absorption of nitro- gen by calcium carbide. Cyanamide also gives rise to two isomeric series of alkyl derivatives. 1. Methyl- and ethyl-cyanamides are prepared from methyl and ethyl thio-urea. Diethyl-cyanamide, CN 2 (C 2 H 5 ) 2 , and its homologues are obtained by the action of alkyl iodides or sul- phates on crude calcium cyanamide (B. 1911, 44, 3149). Acids hydrolyse the ethyl compound to C0 2 , NH 3 , and NH(C 2 H 5 ) 2 , hence it possesses the constitution N C N(C 2 H 6 ) 2 : N!C.N(C 2 H 6 ) 2 + 2H 2 = NH 3 + C0 2 + NH(C 2 H 5 ) 2 . CARBONIC ACID DERIVATIVES 279 2. Other cyanamide derivatives, which are chiefly known in the aromatic series, are derived from a hypothetical isomer of cyanamide, viz. carbo-di-imide, NH:C:NH; for instance, diphenyl-carbodiimide, CN 2 (C 6 H 5 ) 2 . Boiling with acids like- wise decomposes them into C0 2 and an amine, but the latter can only be a primary one. XIII. CARBONIC ACID DERIVATIVES Carbonic acid is a dibasic acid, forming two series of salts, e.g. Na 2 C0 3 and NaHC0 3 . The acid itself, C0 3 H 2 , = 0*XVvTT, is unknown, but may be supposed to exist in the aqueous solution. It is the lowest hydroxy-acid C n H 2n 3 , i.e. it is homologous with gly collie acid, and may be regarded as hydroxy-formic acid. As both hydroxyls are linked to the same carbon atom, the non-existence of the free hydrate is readily understood (see p. 124, &c.). The salts of carbonic acid and several simple derivatives of carbon are usually treated of under inorganic chemistry. The esters, chlorides, and amides of carbonic acid, like the salts, form two series. The normal compounds, e.g. CO(OC 2 H 5 ) 2 , ethyl carbonate, COCL, carbonyl chloride, and CO(NH 2 ) 2 , carbamide or urea, are well characterized, and are very similar to those of oxalic or succinic acid; the acid compounds, e.g. OH.CO.OC 2 H 5 , ethyl hydrogen carbonate, OH.CO.C1, chloro- carbonic or chloroformic acid, and OH-CO-NH 2 , carbamic acid, on the other hand, are unstable in the free state, but form stable salts. Many mixed derivatives are known, e.g. ethyl carbamate, NH 2 CO OEt, which is an ester and an acid amide, analogous to oxamethane (p. 236); C1-CO'OC 2 H 5 , ethyl chloro-carbonate, which is an ester and an acid chloride. A. Esters Ethyl carbonate, CO(OC 2 H 5 ) 2 , is formed by the action of ethyl iodide upon silver carbonate, or by the action of alcohol upon ethyl chloro-carbonate, and therefore indirectly from carbon oxy-chloride and alcohol: CO(OC 2 H 6 ) 2 + 280 XIII. CARBONIC ACID DERIVATIVES It is a neutral liquid of agreeable odour, lighter than water, and boils at 126. Analogous methyl and propyl esters are known, and also esters containing two different alkyl groups. It is a matter of no consequence which of these radicals is introduced first into the molecule, a proof of the symmetrical arrangement of the two hydroxyls. Ethyl hydrogen carbonate, HO CO C 2 H 5 , a type of an acid ester, corresponds exactly with ethyl hydrogen sulphate, but is much less stable, and only known in its salts. Potas- sium ethyl carbonate, KO'COOC 2 H 5 , is obtained by passing C0 2 into an alcoholic solution of potassic ethoxide: C0 2 + KOC 2 H 5 = CO S (C 2 H 5 )K. It crystallizes in glistening mother-of-pearl plates, but is decomposed by water into potassium carbonate and alcohol. B. Chlorides of Carbonic Acid Carbon oxy - chloride, Carbonyl chloride, phosgene, COC1 2 (/. Davij), is the true chloride of carbonic acid and is analogous to sulphuryl chloride, S0 2 C1 2 . It is obtained by the direct combination of carbon monoxide and chlorine in sunlight, and also by the oxidation of chloroform by means of chromic acid. It is a colourless gas, condensing to a liquid below +8, of exceptionally suffocating odour, and is readily soluble in benzene or toluene. As an acid chloride it decomposes violently with water into C0 2 and HC1. It therefore trans- forms hydrated acids into their anhydrides, with separation of water, and converts aldehyde into ethylidene chloride. It yield urea derivatives with secondary amines of the fatty series, and carbamic chlorides with secondary amines of the aromatic (B. 20, 783). Chloro-carbonic acid, Chloro-formic acid, Cl-CO-OH, the half acid chloride of carbonic acid, is analogous to chloroxalic acid (p. 234), but is so unstable that it is unknown in the free state. Its esters, however, e.g. ethyl chloro-carbonate, ethyl chloro-formate, C1.CO-OC 2 H 5 , may be prepared by the action of carbon oxy-chloride upon alcohols (Dumas, 1833): COC1 2 + C 2 H 6 OH = C1.CO.OC 2 H 6 The ethyl ester is a volatile liquid of very pungent odour, which boils at 93. It reacts as an acid chloride, being decom- AMIDES OF CARBONIC ACID 281 posed by water, and is specially fitted to effect the synthetical entrance of the carboxyl group into many compounds. The esters and acid chlorides just described are derived from ordinary carbonic acid, H 2 C0 3 , the analogue of meta* silicic acid, H 2 Si0 3 . Although an ortho-carbonic acid itself, C(OH) 4 , is unknown, certain derivatives are readily prepared. Carbon tetrachloride may be regarded as the chloride of ortho-carbonic acid. It is much more stable than ordinary acid chlorides, and at high temperatures only is it decomposed by alkalis, yielding alkali chloride and carbonate. The esters of ortho-carbonic acid, e.g. ethyl ortho-carbonate, C(OC 2 H 5 ) 4 , are readily obtained by the action of sodium alco- holates on chloropicrin (p. 97). They are colourless oils with fragrant odours. The ethyl ester boils at 158, and the propyl at 224. When hydrolysed, they yield an alkali carbonate and the alcohol. C. Amides of Carbonic Acid The normal amide of carbonic acid is urea or carbamide, NH 2 'CO'NH 2 , the amic acid is carbamic acid, HOCONH 2 . Imido-carbonic acid, HN:C(OH) 2 , would be an imide of car- bonic acid, but it is only known in its derivatives (Sandmeyer, B. 19, 862). The amidine of carbonic acid is guanidine. The "ortho- amide" of carbonic acid, which would possess the formula C(NH 2 ) 4 , is unknown; when it might be expected, guanidine and ammonia are formed instead. The modes of formation of urea and of carbamic acid are exactly analogous to those of the amides in general: 1. By the action of ammonia upon ethyl carbonate: CO(OC 2 H 6 ) 2 + 2NH 3 = CO(NH 2 ) 2 + 2C 2 H 6 -OH. CO(OC 2 H 5 ) 2 + NH 3 2. By the abstraction of the elements of water from car- bonate or carbamate of ammonia. Dry carbon dioxide and ammonia combine together directly to ammonium carbamate, the so-called anhydrous carbonate of ammonia, NH 2 .COj ONH 4 , which is transformed into urea when heated to 135, or when exposed to the action of an alternating current of electricity : NH 2 .CO-ONH 4 = CO(NH 2 ) 2 + H 2 0. 282 XIII. CARBONIC ACID DERIVATIVES 3. By the action of ammonia upon carbonyl chloride and its derivatives : COCl 2 -f4NH 3 = CO(NH 2 ) 2 + 2NH 4 C1. CO(OC 2 H 6 )C1 + 2NH 3 = CO(OC 2 H 5 )NH 2 + NH 4 C1. Carbamic acid, NH 2 .COOH, is known only in the form of derivatives; the ammonium salt, NH 2 CO'ONH 4 , forms a white mass, and dissociates at 60 into 2NH 3 + C0 2 . Its aqueous solution does not precipitate a solution of calcic chloride at the ordinary temperature, since calcic carbamate is soluble in water; but when boiled it is hydrolysed to the carbonate, and calcic carbonate is then thrown down. Urethane, Ethyl carbamate, NH 2 CO OC 2 H 5 , is formed according to method 3, and by the direct union of cyanic acid with alcohol; also from urea nitrate and sodium nitrite in presence of alcohol. It forms large plates, is readily soluble in water, melts at 50, and boils at 184. It acts as a soporific, and on hydrolysis with alkali yields the alkali carbonate, ammonia and ethyl alcohol. One of its hydrogen atoms is replaceable by sodium. Urethane may be employed instead of cyanic acid for certain synthetic reactions (B. 23, 1856). Analogous methyl and propyl esters of carbamic acid are known, and are also termed urethanes. Carbamic chloride, NH 2 'COC1, obtained by the action of hydrogen chloride upon cyanic acid (Wohler, A. 45, 357), and of carbonyl chloride upon ammonium chloride at 400, forms long, compact, colourless needles of pungent odour. M.-pt. 50, b.-pt. 61-62. It reacts violently with water, amines, &c., and serves for the synthesis of organic acids (see these). Ethyl imido-dicarboxylate, NH(C0 2 C 2 H 5 ) 2 , is the imide corresponding with the amide urethane. It may be prepared from the sodium compound of urethane and ethyl chloro- carbonate. It forms colourless crystals, melting at 50. By the exchange of one ethoxy (OC 2 H 5 ) group for an amido (NH 2 ) group, it gives rise to allophanic ester, and by the exchange of two, to biuret (see p. 289). Urea, Carbamide, CO(NH 2 )2, was first found in urine in 1773. It is contained in the urine of mammals, birds, and some reptiles, and also in other animal fluids. An adult man produces about 30 gms. daily, and it may be regarded as the final decomposition product formed by the oxidation of the nitrogenous compounds in the organism. tJREA 283 It may be prepared by the action of ammonia on ethyl car- bonate, ethyl carbamate, or phosgene, and synthetically by the molecular transformation of ammonium cyanate, by warming its aqueous solution or allowing it to stand (cf. pp. 1 and 273): N:C-ONH 4 ^ The reaction is reversible, and hence the process is never complete. When equilibrium is reached, only a very small amount of untransformed cyanate is left, and the equilibrium is practically independent of the temperature. The reaction has been shown to be a typical bimolecular one (Walker and Hambly, J. C. S. 1895, 746). The reaction is represented as follows by Chattaway (P. 1911. 27, 281): NH 4 -N:C:O -* HN:C:0 + HN:C(OH)NH 2 -* It is usually prepared by mixing a solution of potassium cyanate (from the ferrocyanide) with ammonium sulphate and evaporating the mixture (ammonium cyanate is first formed and gradually changes to urea), or by evaporating urine, add- ing nitric acid, and decomposing the separated and purified nitrate of urea by barium carbonate. It is also formed by heating a solution of carbon monoxide in ammoniacal cuprous chloride: CO + 2NH 3 -{- Cu 2 Cl 2 = CO(NH 2 ) 2 + 2HC1 + 2Cu. It crystallizes in long rhombic prisms or needles, has a cooling taste, is very readily soluble in water, also in alcohol, but not in ether. It melts at 132, sublimes in vacuo without decomposition, and when strongly heated yields ammonia, cyanuric acid, biuret, and ammelide. As an amide it is readily hydrolysed by boiling with alkalis or acids, or by superheating with water (cf. Fawsitt, J. C. S. 1904, 1581; 1905, 494): CO(NH 2 ) 2 Nitrous acid reacts with it to produce carbon dioxide, nitrogen, and water: CO(NH 2 ) 2 + 2N0 2 H = C0 2 + 2N 2 + 3H 2 0. Sodium hypochlorite and hypobromite act in a similar manner (Davy, Knop). Hufner's method of estimating urea quantitatively depends upon the measurement of the nitrogen 284 XIII. CARBONIC ACID DERIVATIVES thus obtained (J. pr. Ch., [2], 3, 1 ; cf. also B. 24, Ref. 330). Urea also reacts with bromine and alkalis in much the same manner as the lower acid amides (Hofmann reaction, p. 184), yielding carbon dioxide and the corresponding amine, hydra- zine (C. C. 1905, i, 1227), which is best removed by the addi- tion of benzaldehyde. Urea reacts with an aqueous solution of chlorine, yielding the dichloro-derivative CO(NHC1) 2 . With acids this forms nitrogen trichloride, and with ammonia it yields diurea or paraurazine, CO^^ 00 ( Chattawa y> J - c - s - 1909 > 129, 235). When warmed with alcoholic potash to 100, urea is converted into cyanate of potassium and ammonia. The basic character of the amino groups is greatly weakened in urea by the presence of the negative carbonyl. Among the salts of urea with acids may be mentioned urea nitrate, COISr 2 H 4 , HN0 3 , which crystallizes in glistening white plates, readily soluble in water, but only slightly in nitric acid; also the chloride, oxalate, and phosphate. But like acetamide, urea also forms salts with metallic oxides, especially with mer- curic oxide, e.g. CON 2 H 4 , 2HgO; finally, it yields crystalline compounds with salts, e.g. urea sodium chloride, CON 2 H 4 , NaCl, H 2 (glistening prisms), and urea silver nitrate, CON 2 H 4 , AgN0 3 (rhombic prisms). The precipitate which is obtained on adding mercuric nitrate to a neutral aqueous solution of urea has the formula 2CON 2 H 4 , Hg(N0 3 ) 2 , 3HgO; upon its formation depends Liebig's method for titrating urea. (See the memoirs of Pfluger and Boliland on the subject, e.g. Pflilger, Arch. f. Phys. 38, 575.) Isomeric with urea is the amidoxime, isuret or methane amidoxime, NHiCH-NH-OH, which is obtained from HCN and NH 2 OH; it crystallizes in prisms (see p. 188). Closely related to carbamide, NH 2 CO'NH 2 , is semicar- bazide or semihydrocarbazide, NH 2 CO-NH-NH 2 , which is the half amide and half hydrazide of carbonic acid. It may be prepared from potassium cyanate and hydrazine hydrate. It is a basic substance, melts at 96, and is usually met with in the form of its hydrochloride. It reacts with aldehydes and ketones in much the same manner a^ phenyl-hydrazine, yielding condensation products known as semicarbazones : H 2 O + C 6 H 6 . C(CH 3 ) : N - NH CO NH 2 , UREIDES 285 which crystallize well, and have well-defined melting-points (see p. 136). Alkylated ureas are obtained by the exchange of the amido hydrogen atoms for one or more alkyl radicals. They are produced by Wohler's synthetical method, viz. by the combination of cyanic acid with amines, or of cyanic esters with ammonia or amines, thus : CO-NC 2 H 6 + NH 2 .C 2 H 6 = CO(NH.C 2 H 6 ) 2 . Also from amines and carbon oxy-chloride. As examples may be mentioned: Methyl urea, OCX^j a-Diethyl urea, Ethyl urea, CO; ^Diethyl urea, Certain of them closely resemble urea; others, however, are liquid and volatilize without decomposition. Their constitution follows very simply from the nature of the products which are formed on hydrolysis; thus a-diethyl urea breaks up into carbon dioxide and ethylamine, and the /?- compound into carbon dioxide, ammonia, and diethylamine, in accordance with the generalization enunciated on p. 95, that alkyl radi- cals which are directly united to nitrogen are not separated from it on hydrolysis. Acyl Derivatives. By the entrance of acyl radicals into urea, its acid derivatives or ureides are formed. These are formed by the action of acid chlorides or anhydrides upon urea, or by the action of phosphorus oxy-chloride upon the salts of urea with organic acids. The simple ureides correspond in many respects with acid amides or anilides, have neither distinctly acid nor basic properties, and may be hydrolysed to the acid and urea or its products of decomposition (p. 283). To this class belong acetyl urea, NH 2 .CO.NH.(X).CH 3 , and allophanic acid, NH 2 -CO-NH.C0 2 H. Hydroxy- monobasic acids also form ureides, not only in virtue of their acidic nature, but as alcohol and acid at the same time, thus: Hydantoic acid, nn^-- 2'C0 2 H .NH-CH.CH, . NH -CH 2 Dactyl urea, CO< A O Hydantom, OX' Hydantoi'n or glycolyl urea (needles, neutral) and hydantoic 286 XIII. CARBONIC ACID DERIVATIVES acid or glycoluric acid (prisms), are derivatives of glycollic acid ; the former on hydrolysis yields hydantoic acid, which in its turn is broken up into C0 2 , NH 3 , and glycocoll. They are obtained from certain uric acid derivatives (e.g. allantom) by the action of hydriodic acid, and also synthetically, for in- stance, hydantoic acid from glycocoll and cyanic acid. A methyl-hydanto'in, C 3 H 3 (CH 3 )N 2 2 , results from the partial hydrolysis of creatinine (p. 298), NH being here replaced by 0. Just as the dibasic acids oxalic, malonic, tartronic, and mesoxalic yield amides with ammonia, so with urea they form compounds of an amidic nature. In such reactions either two molecules of water are eliminated, so that no car- boxyl radical remains in the compound, or only one molecule is eliminated and a carboxyl group is retained. In the former case the so-called cyclic ureides are obtained, and in the latter the ureido-acids, e.g. from oxalic acid, parabanic and oxaluric acids : CO-OH co^ 1111 ' 00 co/ NH 3 CO-OH X NH-CO \NH.CO.OO,H Oxalic acid Cyclic ureide (parabanic acid) Ureido-acid (oxaluric acid). In an analogous manner the ureide barbituric acid, C 4 H 4 No0 3 , is derived from malonic acid, the ureide dialuric acid, Cf 4 H 4 N 2 4 , from tartronic acid, arid the ureide alloxan, C 4 H 2 N 2 4 , and ureido-acid alloxanic acid, C 4 H 4 N 2 5 , from mesoxalic acid. These are solid and, for the most part, beautifully crystal- lizing compounds of a normal amidic character, and therefore readily hydrolysed to urea (or C0 2 and NH 3 ) and the respec- tive acid. The ureido-acids may be regarded as half-hydro- lysed ureides, and may be prepared from the latter in this manner. As they contain a carboxyl group, they still possess acidic properties. The constitution of the various cyclic ureides and ureido- acids follows in most cases from the products they yield on hydrolysis, and also from their synthetical methods of for- mation and their relationships to one another. Some of these ureides are obtained synthetically from urea and the requisite acid often in the presence of phosphorus oxy-chloride, e.g. malonyl urea (barbituric acid), from urea and malonic acid. Many can be obtained by the PARABANIC ACID. METHYL URACYL 287 oxidation of various complex natural products, e.g. alloxan or parabanic acid by oxidizing uric acid with nitric acid. Most of the ureides have the character of more or less strong acids. Since this acid character is not to be explained, as in the case of the ureido-acids, by the presence of carboxyl groups, one must assume that it depends upon reasons similar to those which apply in the case of cyanic acid and of suc- cinimide, viz. that the replaceable hydrogen atoms are imido- hydrogen atoms, the acidic nature of which is determined by the adjacent carbonyl groups. This explains, for instance, why parabanic acid is a strong dibasic acid. Only a few of the more important among these compounds can be discussed here. The names given to the majority of them have no relationship to their constitution, and were as- signed to them before the constitutions had been determined. Parabanic acid, Oxalyl urea, C0<^ , is prepared by the action of nitric acid upon uric acid, and crystallizes in needles or prisms soluble in water and alcohol. The salts, e.g. C 3 HKN 2 3 , C 3 Ag 2 N 2 3 , are unstable, being converted by water into salts of the monobasic oxaluric acid, NH 2 -CO NH.CO.C0 2 H, which crystallize well. A methyl - parabanic acid, CO , and a di- methyl - parabanic acid, the so-called " cholestrophane ", , are also known. The former is prepared by the action of nitric acid upon methyl-uric acid, and crystal- lizes in prisms, while the latter is obtained from theine with nitric acid or chlorine water, and also by the methylation of parabanic acid, i.e. from the silver salt and methyl iodide. It crystallizes in plates and distils without decomposition. Methyl- iiracyl, CO<^;^^>CH, is produced by the action of urea upon acetoacetic ester, water and alcohol being eliminated (Behrend, A. 229, 1, and p. 230). When it is treated with nitric acid, a nitro-group enters the molecule, and the methyl-group is oxidized to carboxyl, thus forming 5-nitro-uracyl-4-carboxylic acid, 288 XIII. CARBONIC ACID DERIVATIVES This in its turn can give up carbon dioxide and pass into 5-nitro-uracyl, which yields upon reduction with tin and hydrochloric acid 5-amino-uracyl and isobar bituric acid, 5-hydroxy-uracyl, This last is oxidized by bromine water to isodialuric acid, from which uric acid may be synthesised by warming with urea and sulphuric acid (see p. 291). Barbituric acid, Malonyl urea, CO<;>CH 2 , crys- tallizes in large colourless prisms (+ 2H 2 0). The hydro- gen atoms of the methylene group are reactive (cf. ethyl malonate), and can be replaced by bromine, -NOg, :N-OH, metals, &c. The metallic radicals in their turn can be replaced by alkyl groups. The dimethyl derivative when hydrolysed yields carbon dioxide, ammonia, and dimethyl- malonic acid, thus indicating that the methyl groups have replaced the methylene hydrogen atoms. The e'so-nitroso derivative, CO<^;^>C:N.OH, violuric acid, can also be obtained by the action of hydroxylamine on alloxan, and on reduction yields ammo-barbituric acid (uramil), from which pseudouric and uric acids have been synthesised (p. 291). Diethylbarbituric acid (veronal) is used as a soporific. Dialuric acid, Tartronyl urea, CO<^;^Q>CH.OH, crys- tallizes in colourless needles or prisms which redden in the air. It is a strong dibasic acid, and on oxidation yields allox- an tin. Alloxan, Mesoxalyl urea, C0< ' ^^' ma ^ ^ e P re ~ pared from uric acid by oxidation with cold HNO 3 . It forms large colourless glistening rhombic prisms ( + 4H 2 0), is readily soluble in water, and has strongly acidic properties. It colours the skin purple-red, and with ferrous sulphate solution pro- duces an indigo-blue colour. It combines with NaHSOg, and ** MUREXIDE. ALLANTOIN 289 readily changes into alloxantin. The corresponding ureido- acid, alloxanic acid, NH 2 CO NH . CO CO C0 2 H, which alloxan yields even with cold alkali, forms a radiating crys- talline mass readily soluble in water. Methyl- and di- methyl alloxan are also known, and may be obtained by the action of nitric acid upon methyl-uric acid and caffeine respectively. The diureide alloxantin, C 8 H 4 7 N 4 , stands midway in composition between tartronyl- and mesoxalyl-urea, by the combination of which it is formed. It may also be obtained by the action of H 2 S on alloxan, or directly from uric acid and HN0 3 . It crystallizes in small hard prisms (+ 3H 2 0), which become red in air containing ammonia, their solution acquiring a deep-blue colour on the addition of ferric chloride and ammonia. The tetramethyl derivative, amalic acid, C 8 (CH 3 ) 4 N 4 7 , is obtained by oxidizing theine with chlorine water, and forms colourless crystals which redden the skin and whose solution is turned violet-blue by alkali. Both these compounds yield, upon oxidation, first alloxan or its dimethyl derivative, and then parabanic or dimethyl -parabanic acid. Alloxantin probably has the constitution: When heated with ammonia it is converted into murexide, the acid ammonium salt of purpuric acid, C 8 H 5 N 6 5 , which is the acid form of barbituryl iminoalloxan : NH.CO (J. pr. 1905, [ii], 73, 449), which is formed when uric acid is evaporated with dilute nitric acid, and ammonia added to the residue; this constitutes the "murexide test" for uric acid. Murexide crystallizes in four-sided plates or prisms (+ H 2 0) of a golden-green colour, which dissolve to a purple-red solu- tion in water and to a blue one in potash. The free acid is incapable of existence. Allantoi'n is a diureide of glyoxylic acid, of the constitution . ra-co, and is found in the allantoic liquid of the cow, the urine of (B480) 290 XIII. CARBONIC ACID DERIVATIVES sucking calves, &c. It forms glistening prisms, and can be synthesised from its components. Biuret, NH 2 .CO.NH.(X).NH 2 , is obtained by heating urea at 160: 2NH 2 .(X).NH 2 = NH 3 + NH(CO-NH 2 ) 2 . It crystallizes in white needles ( -f H 2 0), and is readily soluble in water and alcohol. The alkaline solution gives a beautiful violet-red coloration on the addition of a little cupric sulphate the "biuret reaction". Biuret is also formed by the action of ammonia upon the allophanic esters, crystalline compounds sparingly soluble in water, which are prepared from urea and chloro-carbonic esters, thus: CO(NH 2 ) 2 + C1.C0 2 C 2 H 5 = NH 2 .CO-NH.CX) 2 C 2 H 6 + HC1. Allophanic acid itself is not known in the free state, as it immediately breaks up into urea and carbon dioxide. Biuret may be regarded as its amide. The Purine Group (E. Fischer, B. 1899, 32, 435; 35, 2564). A number of relatively complex cyclic diureides derived from 1 molecule of hydroxy dibasic acids and 2 of urea are known. One of the most important of these is uric acid. The parent substance of this group of compounds is purine (E. Fischer, B. 1899, 32, 449). Purine : 2CH5C.NEK8 4 9 is usually obtained from uric acid : NH-CO co r NH.! which reacts with phosphorus oxy-chloride as the tautomeric trihydroxy purine: N = C-OH SYNTHESIS OF URIC ACID 291 yielding the corresponding trichlorpurine : N = CC1 and this on reduction yields purine itself. It is a colourless crystalline compound, melts at 216, and is both an acid and a base. It dissolves readily in water, and is not easily oxidized. The atoms of the ring are usually numbered as indicated. Uric acid is the keto form of 2:Q:8-trihydroxy-purine, and has the constitutional formula: NH-CO CO ' NH-< Uric acid and many other compounds containing the NHCO group, as tautomeric substances, behave in certain reactions as ketonic compounds and in other reactions as hy- droxylic derivatives, i.e. they exhibit keto-enolic tautomerism. It is a common constituent of the urine of most carnivorous animals, whereas that of herbivorous animals contains hippuric acid. It is also found in the blood and muscle juices of the same animals, and would appear to be the oxidation product of the complex nitrogenous compounds contained in the organism. It is also contained in the excrement of birds, serpents, and insects, and in guano. Syntheses. 1. By heating glycocoll with urea (HorlaczewsU, B. 15, 2678). 2. By heating isodialuric acid (p. 288) with urea and concen- trated sulphuric acid (R. Behrend and 0. Roosen, A. 251, 235) : NH-CO NH-CO CO C-OH + H 2 N >CQ m 00 9/ NH \ CO + 2H 2 0. NH-C.OH ^ H^/ NH-C.NH/ 3. By heating cyano-acetic acid with urea (Traube, B. 1891, 24, 3419; 1900, 33, 3035). 4. By heating pseudouric acid with hydrochloric acid when water is eliminated (K Fischer, B. 1897, 30, 559): NH-CO NH-CO CO CH.NH-CO-NH 2 = H 2 O + CO C-NH\ C() NH-CO ' 292 XIII. CARBONIC ACID DERIVATIVES The pseudo acid is obtained as the potassic salt by the condensation of amino-barbituric acid (p. 288) with potassic cyanate : NH.CO NH-CO CO CH-NH 2 -f HCNO = CO CH-NH-CO-NH,, (Baeyer). NH-CO NH.CO It is usually prepared from guano and the excrement of serpents, and crystallizes in small plates; is almost insoluble in water, and quite insoluble in alcohol or ether. Uric acid is a weak dibasic acid; its common salts are the acid ones, e.g. C 5 H 3 3 N 4 K, a powder sparingly soluble in water. The lithium and piperazine salts are somewhat more soluble, and hence are used in medicine for removing uric acid from the human system. When the two lead salts are treated with methyl iodide, methyl- and dimethyl uric acids are obtained, both of which also are weak dibasic acids, since they still contain replaceable imido-hydrogen atoms. Constitution. The constitutional formula, given above, was first proposed by Medicus, and afterwards proved to be correct by E. Fischer (A. 215, 253). The more important arguments used were: (1) Uric acid yields alloxan and urea when cautiously oxidized, this proving that we have to deal here with a carbonic acid derivative and a carbon chain, CCC; (2) uric acid contains four imido groups, since, by the intro- duction of four methyl groups, one after the other, four mono- methyl, various di- and trimethyl, and one tetramethyl uric acids are obtained. When the tetramethyl acid is hydrolysed with concentrated hydrochloric acid all the nitrogen is elimi- nated as methylamine, and thus each methyl group is probably attached to a nitrogen atom; (3) dimethyluric acid yields methylalloxan and methylurea on oxidation. Uric acid is usually recognized by its sparing solubility, and by its giving the murexide test. Xan thine, 2:Q-Dihydroxy-purine, or the corresponding keto form: NH-CO NH.CO co C.NH\ CH C.NH\ NH-C-N/ C N_C-N/ H ' Xanthine Hypoxantkiue DERIVATIVES 293 may be obtained by the reduction of uric acid with sodium amalgam, or by the action of nitrous acid on guanine (amino hypoxanthine). It is a white amorphous mass, and is both basic and acidic. The lead salt, C 5 H 2 PbN 4 2 , is converted into theobromine by methyl iodide. (Of. B. 1897, 30, 2235; 1900, 33, 3035.) When oxidized it yields the same products as uric acid. Hypoxanthine, Sarcine, or Q-oxy-purine, is sparingly soluble in water and closely resembles xanthine, Theobromine, 3 : 1-Dimethyl-xanthine, NH CO NMe-00 CO C-NMex CO C.NMe\ NMe C N/ NMe . C N/ ' Theobromine Caffeine occurs in the beans of cacao; it is a crystalline powder of bitter taste, and is only sparingly soluble in water and alcohol. It forms salts both as a base and as an acid. The silver salt, C r H 7 AgN 4 2 , when treated with CH 3 I, yields caffeine or theine, I:3:7-trimethyl-xanthine, which occurs in tea (2-4 per cent), coffee, and various plants. (For synthesis from dimethyl urea and malonic acid, see Fischer, B. 1895, 28, 3137; 1899, 32, 435; from cyanoacetic acid, 1900, 33, 3035.) It crystal- lizes (+ H 2 0) in beautiful long glistening silky needles of faintly bitter taste, which are sparingly soluble in cold water and alcohol, and can be sublimed. The salts are readily de- composed by water. Chlorine oxidizes it to dimethyl alloxan and monomethyl urea. Theophylline, 1 : 3-dimethyl-xanthine, also occurs in tea. Guanine, 2-amino-Q-oxy-purine, or 2-amino-hypoxanthine, and adenine, Q-amino-purine, both contain amino-groups, and are thus basic substances. Both compounds, together with xan- thine and hypoxanthine, are formed by the decomposition of the nucleic acids and other complex compounds contained in the animal system. The constitution follows largely from (1) basic properties, (2) their conversion respectively into xanthine and hypoxanthine by the aid of nitrous acid, and (3) from their oxidation products. A summary of some of the more important ureides which can be obtained from uric acid are tabulated here: t-t o X W o A w g -.8 v o o V o si^ill^ljssi 8 SULPHUR DERIVATIVES OF CARBONIC ACID 295 D. Sulphur Derivatives of Carbonic Acid In addition to most of the carbonic acid derivatives which have been described, there exist analogous compounds in which the oxygen is wholly or partially replaced by sulphur. Many or these again are unstable in the free state, from the fact of their being too readily hydrolysed to C0 2 , COS, or CS 2 , but they are known as salts, or at least as esters. The latter are often not real esters, in so far that those which contain an alkyl radical linked to sulphur do not yield the corresponding alcohols on hydrolysis, but mercaptans, in accordance with the intimate character of this linking. Various mono-, di-, and tri-thio-derivatives of carbonic acid are known, according as 1, 2, or 3 of the oxygen atoms are replaced by sulphur. Many of the thio-acids react as tautomeric substances, and give rise to isomeric alkyl derivatives in exactly the same manner as hydrocyanic, cyanic, and thiocyanic acids. Thiophosgene, Thiocarbonyl chloride, CSC1 2 . When chlorine is allowed to act upon carbon disulphide, there is first formed the compound CC1 3 'SC1, which is converted into thiophosgene by SnCl 2 . It is a red, mobile, strongly fuming liquid of sweetish taste, which attacks the mucous membrane, and boils at 73. In its chemical behaviour it closely resembles phosgene, but is much more stable towards water than the latter, being only slowly decomposed even by hot water. With ammonia it yields ammonium thiocyanate and not thiocarbamide. Thiocarbonic Acids. Tri-thiocarbonic acid is made up of the constituents CS 2 + H 2 S, so that carbon disulphide is its thio-anhydride, while the di-thiocarbonic acids contain the elements of CS 2 + H 2 or of COS + H 2 S, and the mono- acids those of COS + H 2 or of C0 2 + H 2 S. We find accordingly that CS 2 combines with Na 2 S to CS 3 Na 2 , sodic tri- thiocarbonate, with KSC 2 H 5 to CS(SC 2 H 5 )SK, with KOC 2 H 5 (i.e. an alcoholic solution of potash) to CS(OC 2 H 5 )SK, potas- sium xanthate. In a similar manner COS and CSC1 2 combine with mercaptides and alcoholates. Tri-thiocarbonic acid, CS 3 H 2 , is a brown oil, insoluble in water, and readily decomposed, and its ethyl ester, S:C(SC 2 H 5 ) 2 , a liquid boiling at 240. Potassium xanthate, S:C<g^ H5 , obtained by the action of potassic ethoxide, (KOH + C 2 H 6 OH), on carbon disulphide, 296 XIII. CARBONIC AClt> DERIVATIVES crystallizes in beautiful colourless needles, very readily soluble in water, less so in alcohol. A solution of cupric sulphate throws down cupric xanthate as a yellow unstable precipitate, hence the name. It is employed in indigo printing. The free xanthic acid, or ethyl hydrogen dithiocarbonate, CS(OC 2 H 5 )SH, is an oil insoluble in water, and decomposes at so low a tem- perature as 25 into carbon disulphide and alcohol. Thiocarbamic Acids. Di-thiocarbamic acid, NH 2 CS-SH, is formed as ammonic salt by the combination of CS 2 and NH 3 in alcoholic solution : CS 2 + 2NH 3 = NH 2 .CS-SNH 4 . The free acid is a reddish oil which easily decomposes into thiocyanic acid and sulphuretted hydrogen: NH 2 .CS-SH = CSNH + SELj. Carbon disulphide combines in an analogous manner with primary amines to form the aminic salts of alkylated di-thio- carbamic acids; thus ethylamine yields ethylamine ethyl-di- thiocarbamate, C 2 H 5 NH.CS.SNH 3 C 2 H 5 . When such salts are heated above 100, H 2 S is evolved and a dialkyl-thio- urea left behind, e.g. diethyl-thio-urea, CS(NHC 2 H 5 ) 2 ; when HgCl 2 or AgN0 3 is added to their solutions, the Hg or Ag salts of the acids are precipitated, and these decompose on boiling with water into HgS or Ag 2 S and the corresponding mustard oil (cf. p. 275): 2CS(NHC 2 H 5 ).SAg = 2CSNC 2 H 5 + Ag 2 S + H 2 S. Secondary amines also give rise to alkylated di-thiocarbamic acids, but the latter do not yield mustard oils. Thiocarbamide, Thio-urea, sulpho-urea, S:C(NH 2 ) 2 (Reynolds), is the analogue of urea, and its modes of formation are exactly similar to those of the latter. Thus it is formed from am- monium thiocyanate just as urea is from the cyanate: N:C.SNH 4 ^ CS(NH 2 ) 2 . To effect this molecular transformation a temperature of at least 130 is required, and it is only partial, as the reaction is reversible. At 170 equilibrium is attained after 45 minutes, and the mixture then contains only 25 per cent of thiocarba- mide (Reynolds and Werner, P. 1902, 207). It may also be AMIDINES OF CARBONIC ACID 297 formed by the direct union of sulphuretted hydrogen with cyanamide: CN.NH 2 + SH 2 = CS(NH 2 ), Thiocarbamide crystallizes in rhombic six-sided prisms, or if not quite pure in long silky needles, readily soluble in water and alcohol. M.-pt. 172. It is easily hydrolysed to C0 2 , H 2 S, and 2NH 3 . HgO abstracts H 2 S from it, with for- mation of cyanamide. Cold permanganate of potash solution oxidizes it to urea. As a weak base it forms salts with acids, but at the same time it yields salts with HgO and other metallic oxides; it also combines with salts, such as AgCl, PtCl 4 , &c. When heated with alcoholic potash to 100, it is reconverted into (the potassium salt of) thiocyanic acid and ammonia. Thiocarbamide gives rise to alkyl derivatives (normal and pseudo), acyl derivatives, cyclic ureides, &c., in much the same manner as urea itself. E. Amidines of Carbonic Acid Guanidine, or Imino-carbamide, NH:C(NH 2 ) 2 (Strecker, 1861), may be obtained by the oxidation of guanine, also by heating cyanamide with ammonium iodide, and therefore from cyanogen iodide and ammonia: = CN 3 H 5 ,HI. It is usually prepared by heating thio-urea with ammonium thiocyanate to 180-190, and therefore from the thiocyanate alone at this temperature ( Volhard) : CS(NH 2 ) 2 + NH 4 -CNS = C(NHXNH 2 ) 2 , CNSH + H 2 S Guanidine isothiocyanate. Guanidine crystallizes well, is readily soluble in water and alcohol, deliquesces in the air, and is a sufficiently strong monoacid base to absorb carbon dioxide. Guanidine car- bonate, (CN 3 H 5 ) 2 , H 2 C0 3 , crystallizes beautifully in quadratic prisms. The base is readily hydrolysed, at first to urea and ammonia, and finally to ammonia and carbon dioxide. By the action of a mixture of nitric and sulphuric acids upon guanidine nitrate, nitro-guanidine, NH 2 'C(NH)NHN0 2 , is obtained, which is readily reduced to amino-guanidine, NH 2 C(NH)NH NH 2 . The latter, when boiled with alkalis or acids, breaks up into hydrazine, N H 4 , ammonia, and carbon 298 XIII. CARBONIC ACID DERIVATIVES dioxide, and it yields with nitrous acid diazo - guanidine, NH 2 C(NH)NHN:N-OH, which in its turn is decomposed by alkalis into water, cyanamide, and hydrazoic add, N 3 H (Curtius, A. 1900, 314, 339). By the direct combination of cyanamide with glycocoll there is formed glycocyamine : NH;C \NH 2 .CH 2 .C0 2 H, which readily loses water with formation of glycocyamidine : If, instead of glycocoll, its methyl derivative, sarcosine, is used, we obtain in an analogous manner creatine and ereatinine (Folhard): e.CH 2 .C0 2 H Creatine Creatinine. Creatine is present in the juice of muscle, and is prepared from extract of meat (LieUg). It crystallizes in neutral prisms (+ H 2 0) of a bitter taste, is moderately soluble in hot water, but only slightly in alcohol. When heated with acids it loses water and yields ereatinine, which is an invari- able constituent of urine, and which forms a characteristic double salt with zinc chloride, 2C 4 H r N 3 + ZnCl 2 . It is a strong base and much more readily soluble than creatine. Creatinine is the methyl derivative of imino-hydantoin, and as such yields, when carefully hydrolysed, ammonia and methyl- hydantoi'n. XIV. CARBOHYDRATES Most of the carbohydrates which occur in nature have been known for a long time. Cane-sugar was found in the sugar- beet by Marggrafm 1747, and dextrose in honey by Glauber. The transformation of starch into glucose (p. 309) was first observed by Kirchoff in 1811. The name carbohydrate was formerly applied to certain substances which occur naturally in large quantities in the vegetable and animal kingdom, and which could be repre- CARBOHYDRATES 299 sented by the general formula C x (H 2 0) y , where x = 6 or a multiple of 6, ..^dextrose ,C 6 (H 2 0) 6 or C 6 H 6 , cane-sugar, C i 2 (H 2 0) n or C ]2 H 22 O n , and starch [C fl (H 2 0)J x . In addition to these natural products, the group at the present time includes a number of compounds which have only been ob- tained synthetically, mainly as a result of the researches of E. Fischer. The number of carbon atoms in these varies considerably. Carbohydrates are now known in which the hydrogen and oxygen are not present in the proportions of 2 atoms of hydrogen to 1 of oxygen, e.g. rhamnose, C 6 H 12 5 . The carbohydrates are usually divided into the three fol- lowing groups, according to their relative complexity: A. Monosaceharoses. This is the simplest group of the carbohydrates, and the members are all polyhydroxy alde- hydes or ketones containing from 3-9 carbon atoms. The group includes the common substances arabinose, C 5 H 10 5 , and the isomeric compounds, C 6 H 12 6 , glucose or grape-sugf.r, and fructose or fruit-sugar. As a rule, the compounds are readily soluble in water, have a sweet taste, and do not crystallize very readily. B. Bi- and Trisaccharoses. These compounds may be regarded as anhydrides of the monoses, usually derived by the elimination of 1 molecule of water from 2 mols. of a monose, or of 2 mols. of water from 3 of a monose. It is not necessary that the 2 or 3 molecules of monose should be iden- tical in structure, e.g. cane-sugar is the anhydride produced by the elimination of 1 mol. of water from 1 mol. of glucose and 1 of fructose. As anhydro-derivatives they are readily hydro- lysed by mineral acids, yielding the monoses, from which they may be regarded as being derived. Most of the di- and trioses are soluble in water, crystallize very well, and also possess a sweet taste. Examples are cane- sugar, maltose, and milk-sugar. C. Polysaccharoses or Polyoses, This group includes the complex carbohydrates, such as starch, cellulose, &c. They may be regarded as derived from the monoses by the elimi- nation of x mols. of water from x mols. of a monose, e.g. : #C 6 H 12 6 - #H 2 = (C 6 H 10 6 ) X . In conformity with such a structure they are fairly readily hydrolysed, yielding as the ultimate product a monose. As a rule, they do not dissolve in water, possess no sweet taste, and have not been obtained in a crystalline form. 300 XIV. CARBOHYDRATES A. Monosaeeharoses These are all open-chain polyhydroxy-aldehydes or ketones, OH CH 2 CH(OH) . CH(OH) CH(OH) - OH : O Arabinose, OH CH 2 CH(OH) CH(OH) CH(OH) CO CH 2 OH Fructose, and are divided into the two main groups aldoses and ketoses, according to their aldehydic or ketonic constitution. As a rule, several hydroxyl groups are present in addition to the aldehydic 'C^ or ketonic ^>C:0 group, and invariably one of these hydroxyl groups is in the a-position with respect to the aldehydic or ketonic group. The monoses are usually divided into sub-groups, according to the number of oxygen atoms present in the molecule, e.g. : Trioses, OH.CH 2 .CH(OH).CH:0 and OH.CH 2 .CO-CH 2 .OH; Tetroses, OH.CH 2 .(CH.OH) 2 .CH:0; Pentoses, OH.CH 2 .(CH.OH) 3 .CH:O and CH 8 .(CH.OH) 4 .CH:0; Hexoses, OH.<JE 2 .(CH.OH) 4 .CH:O and OH.CH 2 .(CH.OH) 3 .CO-CH 2 .OH; Heptoses, OH CH 2 (CH OH) 5 CH : O ; Octoses, OH.CH 2 .(CH.OH) 6 .CH:0; Nonoses, OH-CH 2 .(CH-OH) 7 .CH:O. As a rule, the molecule of any single monose contains several asymmetric carbon atoms, e.g. a hexose, OHCH 2 (CH-OH) 4 CH:0, contains 4 asymmetric carbon atoms, and hence should exist in 2 4 , i.e. sixteen distinct optically active modi- fications, in addition to eight racemic forms. In most cases all the possible stereo-isomeric modifications are not known, but the number of such compounds known has been largely increased within recent years owing to the brilliant researches of Emil Fischer (B. 1890, 23, 2114; 1894, 27, 3189). General Characteristics of Aldoses. As aldehydes the aldoses possess most of the properties already described as characteristic of fatty aldehydes. They are readily reduced by ordinary alkaline reducing agents, yielding polyhydric alcohols: PROPERTIES OF ALDOSES 301 When oxidized, they yield first mono- and then dibasic acids, containing the same number of carbon atoms : OH.eH 2 .(CH.OH) 4 .CH:0 OH.CH 2 .(CH.OH) 4 .CO.OH COOH.(CH.OH) 4 .COOH. These reactions are of considerable importance as direct evidence of the aldehydic nature of the aldoses. The first stage of the oxidation is effected by mild oxidizing agents, such as chlorine, bromine water, silver oxide, or ammoniacal solutions of cupric salts. The last-mentioned reaction is the basis of the usual volumetric method for the estimation of glucose and other aldoses. The aldose solution is added to a given volume of a standard Fehlintfs solution (a solution con- taining cupric sulphate, sodic ammonic tartrate, and sodic hydroxide (p. 253) ) until the blue colour just disappears on boiling. An even more exact method is to weigh the cuprous oxide (as such, as metallic copper, or as cupric oxide) formed by reducing a given volume of the sugar solution with an excess of Fehling's solution. The oxidation to a dibasic acid requires somewhat stronger oxidizing agents, e.g. nitric acid. Although the aldoses do not combine directly with ammonia or sodic hydric sulphite, they readily form additive compounds with hydrogen cyanide : OH CH 2 (CH OH) X CH : + HCN = OH.CH 2 (CH.OH) X .CH(OH).CN. This is an extremely important reaction as being the basis of a method for passing from a tetrose to a pentose, or from a pentose to a hexose (see p. 304). They react normally with hydroxylamine, yielding oximes, more especially in alcoholic solution, and the oximes thus obtained may be converted into a monose containing a smaller number of oxygen atoms (p. 305). They can also react normally with phenyl-hydrazine, yield- ing phenyl-hydrazones, which, as a rule, are sparingly soluble, colourless, crystalline compounds with definite melting-points. These are readily transformed back into the aldoses by treat- ment with hydrolysing agents or with benzaldehyde (A. 1895, 288, 140). One of the most characteristic properties of monoses is the formation of osazones or diphenyl-hydrazones. This reaction may be regarded as taking place in three distinct stages: (a) Formation of a phenyl-hydrazone, XCH(OH) 304 XIV. CARBOHYDRATES The ketoses also form metallic derivatives and acetyl deriva- tives. Alcoholic Fermentation of Monosaccharoses. Many of the natural products, e.g. d-glucose and ^-fructose, are readily fer- mented by yeast (Saccharomyces), yielding as chief products ethyl alcohol and carbon dioxide (p. 76). This decomposition is undoubtedly due to the presence of an enzyme, Buchner's zymase, which is contained in the cells of the organism. Fischer's researches have shown that all monoses cannot be fermented, only certain of those containing 3 or a multiple of 3 carbon atoms. Even such monoses are not all readily fer- mented, e.g. ^-glucose is fermented more readily than /-glucose, and the isomeric guloses cannot be fermented by yeast. There appears to be an intimate relationship between the configura- tion of the monose molecule and of the ferment (enzyme) which is capable of decomposing it. Fischer has compared this relationship to that of a lock and its corresponding key. Conversion of an Aldose into an Isomeric Ketose. This is an interesting transformation due to E. Fischer, and consists in converting the aldose into its osazone, which on hydrolysis with hydrochloric acid yields phenyl-hydrazine and a poly- hydroxy-ketonic aldehyde, usually known as an osone. When the osone is reduced, the aldehydo-group is converted into a primary alcoholic radical, and a hydroxy-ketone (ketose) iso- meric with the original aldose is obtained, e.g. : X-CH(OH).CH:0 X.C(:N-NHPh).CH:N.NHPh X.CO-CEVOH - X.CO-CH-.O. By this means d-glucose can be transformed into ^-fructose. Synthesis of a Mono saccharose from a Simpler Mono- saccharose. The aldose is converted into its cyanhydrin by- means of hydrogen cyanide (Kiliani): X.CH(OH).CH(OH).CH:0 As this reaction involves the introduction of a further asymmetric carbon atom into the molecule, two distinct optically active nitriles will be formed. As the two com- pounds are not related to one another as object to mirror image, they will not be optical antipodes, and will not neces- sarily be formed in equal amount. The mixture of cyanides is hydrolysed, the resulting hydroxy acids converted into lactones CONVERSION OF A MONOSE INTO OTHER MONOSES 305 and then reduced with sodium amalgam, when a mixture of two sugars is obtained: X.CH(OH).CH(OH).CH(OH).C0 9 H -^ X.CH.CH(OH).CH(OH).CO I X.CH(OH).CH(OH).CH(OH).CH:0. As examples of this we have : /3-Galaheptose. By similar methods E. Fischer has succeeded in preparing octoses and nonoses. Conversion of a Monosaccharose into a Simpler Mono- saccharose (Wohl, B. 1893, 26, 730). The aldose is converted into its oxime, which reacts with acetic anhydride, yielding an acetylated hydroxy-nitrile, e.g.: OH.CH 2 .[CH.OH] 4 .CH:N.OH OAc.CH 2 .[CH.OAc] 4 .CN. The nitrile when treated with ammoniacal silver nitrate solu- tion loses hydrogen cyanide and yields the acetyl derivative of a lower monose, e.g. : Ac CH 2 [CH O Ac] 3 . CHO, from which the monose itself is readily obtained. Another method has been worked out by Buff (B. 1898, 31, 1573; 1902, 35, 2360). This consists in oxidizing the aldose to the corresponding monobasic acid, and then oxidizing the calcic salt of this with ferric acetate and hydrogen peroxide. In this way carbonic acid is split off and an aldose obtained : OH.CH 2 .(CH.OH) 3 .CH.(OH).CO-OH + O = OH.CH 2 (CH.OH) 3 .CH:0 + H 2 C0 3 . The aldose can be isolated as its phenylhydrazone, and this with benzaldehyde yields the free aldose. Trioses. When glycerol is oxidized with dilute nitric acid (B480) U 306 XIV. CARBOHYDRATES or other oxidizing agents, a product C 3 H 6 3 is obtained, which has been termed glycerose. This has been shown to consist of the ketone, dihydroxyacetone, OH-CH 2 COCH 2 - OH, with a small amount of the isomeric aldehyde, glycer- aldehyde, OH . CH 2 . CH(OH) . CH : 0, and may be regarded as the simplest monose. It is a syrup, possesses most of the characteristic properties of the monoses, and when warmed with alkalis undergoes condensation and yields a hexose (o-acrose) (p. 312) which closely resembles fructose. Tetroses, C 4 H 8 O 4 . A tetrose, erythrose, can be obtained by the oxidation of erythritol, OH CH 2 [CH OH] 2 CH 2 OH, with nitric acid, and is probably a mixture of an aldose and ketose. Other tetroses can be obtained from the pentoses by the general methods described on p. 305. Pentoses. The pentoses are characterized by the fact that they yield furfuraldehyde or methyl-furfuraldehyde upon pro- longed boiling with hydrochloric acid, water being eliminated. This reaction is largely made use of for their quantitative esti- mation (B. 1892, 25, 2912; 1898, 30, 2570). Arabinose gives furfuraldehyde itself, while its homologue, rhamnose, gives methyl-furfuraldehyde. When warmed with hydrochloric acid and phloroglucinol, cherry-red colorations are produced. The pentoses do not appear to exist free in the animal or vegetable kingdom, but are readily formed by the hydrolysis of various natural gummy carbohydrates. J-Arabinose, C 5 H 10 5 , = OH.CH 2 .[CH.OH] 3 .CH:0, is pro- duced by boiling gum-arabic, cherry gum, or beet-root chips with dilute sulphuric acid, and forms prisms which dissolve in water to a dextro-rotatory solution. It combines with hydrogen cyanide, and thus yields the nitriles of two stereo- isomeric hydroxy-caproic acids, viz. Z-mannonic acid (Kiliani, B. 20, 339, 1233) and Z-gluconic acid (E. Fischer). In addition to /-arabinose, a d-arabinose and a d-l- or racemic arabinose are also known. They are related to one another in exactly the same manner as /-, d-, and r-tartaric acid. The corre- sponding alcohol is arabitol. /-Xylose, or Wood-sugar, is stereo-isomeric with arabinose. and is prepared by boiling wood-gum, straw, and jute with dilute sulphuric acid, and is very similar to arabinose. (Foi its constitution, see B. 24, 537.) The corresponding alcohol is xylitol. Ribose (B. 1891, 24, 4214) and Lyxose (B. 1899, 33, 1798) are stereo-isomeric with arabinose. Rhamnose, or Isodulcite, C 6 H 12 6 , = CH 3 . [CH OH] 4 . CH : 0, ALDOHEXOSES 307 is obtained from several glucosides, e.g. quercitrin or xantho- rharanin (yellow needles, present in French berries, Ehamnus tinctoria, &c.), by the action of dilute sulphuric acid. It forms colourless crystals which contain 1H 2 0, melts at 93, and when distilled with sulphuric acid yields a-methyl-furfuralde- hyde. Several isomerides of rhamnose are known, e.g. fucose from sea-weed, quinovose, rhodeose, and isorhamnose. Hexoses. The hexoses constitute the most important group, as they contain all the more common natural mono- saccharoses, e.g. d-glucose, ^-fructose, d-galactose, &c. These occur in the free state in the juices of ripe fruits, and are also found combined with acids and other compounds in the ether- or ester-like compounds known as glucosides. They are also formed by the hydrolysis of more complex carbo- hydrates, e.g. cane-sugar, maltose, milk-sugar, or starch, either under the influence of mineral acids or of enzymes. They are sweet and for the most part crystalline compounds readily soluble in water, sparingly in absolute alcohol, and insoluble in ether. They possess the chemical properties of pentahydroxy- aldehydes and ketones. Aldohexoses. The common aldohexoses have the con- stitution represented by the formula: In this formula the 4 carbon atoms contained within the brackets are asymmetric carbon atoms, and hence such a compound should exist in numerous stereo-isomeric forms, It can be shown that in this case the number of optically active isomerides theoretically possible is sixteen; of these some eleven are actually known, namely: Dibasic Acid, M.-p. of Aldohexose. Monobasic Acid. COaH[CH-OHVCO a H. Alcohol. Osazone. d- & J-Mannose d- & Z-Mannonic acid d- & Z-Mannosaccharic d- & Z-M annitol 206* d-&Z-Glucose d-&Z-Gluconic acid d-&Z-Saccharic d-&Z-Sorbitol Ibid d-&J-Gulose d-&l-Gnlouic acid d-&Z-Saccharic d-&Z-Sorbitol 157-159* d-&Mdose d-&Mdonic acid Idosaccharic d-&Mditol 193' d-&Z-Galactose d-&Z-Galactonicacid t-Mucic i-Dulcitol 193" d-Talose d-Talonic acid Talomucic d-Talitol 193* All of these hexoses have to be represented by the same structural formula, and only differ as regards the spatial arrangements of the various radicals within the molecule. All are optically active in solution, and the majority form 308 XIV. CARBOHYDRATES pairs of optical antipodes, e.g. d- and Z-glucose, which are related in exactly the same manner as d- and Z-tartaric acids. The members of such a pair are identical as regards their ordinary chemical and physical properties, with the exception of their effects on polarized light, and their behaviour towards enzymes or ferments generally. As a rule, one of the two compounds exists naturally, e.g. d-glucose, and the second must be prepared by artificial means. The two are able to form a racemic compound, which differs as regards its physical properties from the active components. The determination of the configuration of each aldohexose has been accomplished by E. Fischer largely from a study of the following points: (a) The relationship of the aldohexose to the aldopentoses, e.g. Z-arabinose can be transformed into a mixture of /-glucose and /-mannose, and hence in all three compounds the configuration of the following part of the molecule OH CH 2 CH(OH) CH(OH) . CH(OH>- must be identical, (b) The nature of the dibasic acid formed on oxidation, or of the alcohol formed on reduction. When reduced, ^-galactose yields an inactive hexahydric alcohol, viz. i-dulcitol, and from this it follows that in the ^-galactose molecule the H and OH radicals must be so spatially arranged that when the -CHiO group is converted into a CH 2 -OH group a symmetrical molecule is obtained (see formula below), (c) The nature of the osazone; e.g. ^-glucose and d-mannose both give rise to the same osazone d-glucosazone and hence the spatial arrangements of the two molecules must be identical, with the exception of the part CH(OH) CH : 0. As the result of such methods, the following configurations have been arrived at for some of the commoner aldohexoses (B. 1891, 24, 2683; 1894, 27, 3211): CHO CHO CHO CHO HO-C.H H-C.OH H-C-OH H-C-OB HO-C.H H.C-OH HO-C.H HO-C.H H.C-OH HO-C.H H-C-OH HO-C.H H-C-OH HO-C-H H-C-OH H-C-OH CH 2 .OH CH 2 OH CH 2 OH CH 2 OH d-Mannose i-Mannose cZ-Glucose <2-Galactose, 309 E. Fischer has suggested the following system of nomen- clature. According to the Geneva Congress, the name for glu- cose is hexanepentolal. Fischer suggests that the asymmetric carbon atoms be numbered with respect to the CHO group, and that when the H is to the left and OH to the right of an asymmetric carbon atom, it is termed -f and the reverse Thus: e?-Glucose is hexanepentolal, -j \- -f- Z-Glucose 1 c?-Mannose J- -}- rf-Galactose -\ \- d-Gulose 1 rf-Idose + - + - d-Talose \- d-Glucose, Grape-sugar or dextrose, C 6 Hj 2 6 + H 2 0, occurs together with ^-fructose in most sweet fruits, in honey, also in diabetic urine. It is prepared by the hydrolysis of more com- plex carbohydrates, e.g. sucrose or starch. The usual method, the hydrolysis of starch with dilute sulphuric acid, yields a product which contains, in addition to dextrose, dextrine and unfermentable substances. It crystallizes from water in nodular masses made up of six-sided plates which melt at 86, and from methyl alcohol in small anhydrous prisms free from water; m.-pt. 146. It is dextro-rotatory, [a] D = 52-6, hence the name " dextrose ". A freshly-prepared solution turns the plane of polarization almost twice as much as one which has been kept or heated to boiling, a phenomenon which is known as "bi-, multi-, or muta-rotation ". (For explanation, cf. chapter on Physical Constants and Constitution.) The strength of a solution of glucose is usually determined polarimetrically from its specific rotatory power, or gravimetrically by determining the weight of cuprous oxide obtained by the reduction of Fehling's solution with a given volume of the solution (cf. p. 301). d-Glucose-plienyl-hydrazone, C 12 H 18 N 2 5 , forms fine crys- tals which melt at 115. Another modification melts at 144. d-Phenyl-glucosazone crystallizes in sparingly soluble needles. The rotation produced by the hydrazones and osa- zones may be the opposite of that of the mother substance. It is an important point for the recognition of the latter. d-Pentacetyl- glucose, VJLMQC&jS)* melts at 111. d-Glucosone, CH 2 (OH).[CH(OH)] 3 .t50.CHO, forms a syrup which does not ferment with beer yeast, and which yields 310 XIV. CARBOHYDRATES the osazone immediately with phenyl-hydrazine. Methyl glucoside, OH.CH 2 .CH(OH).CH.(CH.OH) 2 .CH.OCH3, exists in two stereo-isomeric modifications, melting at 165 and 107. /-Glucose resembles e-glucose closely, excepting that it turns the plane of polarization as strongly to the left as the latter does to the right. i-Glucose, from i-gluconic acid, is a colourless syrup. The osazone, i-glucosazone, melts at 216, and, apart from rotatory power, is deceptively like the d- and -osazones. Constitution of ^-Glucose, Its constitution as a penta- bydroxy aldehyde follows from the formation of a pentacetyl derivative, and from its oxidation first to a monobasic acid (gluconic acid) and then to a dibasic acid (saccharic acid), both of which contain the same number of carbon atoms as glucose. A proof both of its aldehydic nature and of the normal structure was afforded by Kiliani (B. 1886, 19, 767), who prepared the cyanhydrin, hydrolysed this to the hexa- hydroxy-carboxylic acid, and, by reducing this with hydriodic acid and phosphorus, obtained w-heptylic acid : OH.CH 2 .(CH.OH) 4 .CH:O OH.CH 2 .(CH.OH) 4 -CH(OH).CN CH 3 .(CH 2 ) 5 .C0 2 H OH.CH 2 .(CH.OH) 6 .C0 2 H a product which could not have been produced if the glucose had possessed either a ketonic or an iso-chain (cf. Fructose). (For configuration, see p. 308.) rf-Mannose is stereo-isomeric with d-glucose, and is formed together with e-fructose by the cautious oxidation of mannitol, also by boiling the reserve cellulose of the seed of the Brazil- nut with dilute hydrochloric acid, and by reducing mannonic acid lactone with sodium amalgam. It forms a colourless amorphous mass readily soluble in water, is dextro-rotatory, [alp = +14 *36, and yields the same osazone as ^-glucose. When treated with sodium amalgam it passes readily into d-mannitol. The hydrazone melts at 195, and is sparingly soluble in water. z-Mannose forms a colourless syrup. The osazone is identical with that from t-fructose. /-Mannose is not so readily fermented as the ^-isomeride. d-Galactose is formed together with ^-glucose by the hydro- lysis of milk-sugar with dilute acid, and also from certain gums. It crystallizes in slender needles, melts at 166, is KETOHEXOSES 311 dextro-rotatory, [a] D = +80-3, and readily fermented. Its pentacetyl derivative melts at 143, a-methylgalactoside at 111, and the stereo-isomeric /^-compound at 173-175. Talose is a syrup. The phenyl-hydrazone is very readily soluble in water (difference from galactose). Ketohexoses, OH.CH 2 .[CH.OH] 3 .CO.CH 2 .OH, are struc- turally isomeric with the aldohexoses. As ketones they can- not be oxidized to acids containing the same number of carbon atoms (cf, pp. 68 and 303). The formula contains 3 asym- metric carbon atoms, and hence numerous stereo-isomerides are theoretically possible. ^-Fructose, Fruit-sugar or Icevulose, C 6 H 12 6 , is almost invari- ably found along with d-glucose in the juice of sweet fruits and also, together with the latter, in honey. It is formed along with d-glucose by the inversion of cane -sugar, and together with d-mannose by the cautious oxidation of d-man- nitol; also from d-phenyl-glucosazone, and therefore indirectly from d-glucose. It is most easily prepared by heating inulin (p. 319) with very dilute acid (B. 23, 2084); is somewhat diffi- cult to obtain crystalline, and then forms hard, anhydrous, rhombic crystals melting at 95. It is laevo-rotatory, although belonging genetically to the ^-series. Its power of rotation is almost double that of /-glucose. It may be separated from ^-glucose by means of its sparingly soluble lime compound. Its close relationship to ^-glucose is shown by the fact that it yields the same osazone, and on reduction yields a mixture of d-mannitol and d-sorbitol. On oxidation it yields glycollic and tartaric acids, or glycollic and trihydroxy-butyric acids. With methyl-phenyl-hydrazine it yields a colourless osazone. It is fermentable, but not so readily as d-glucose. I- Fructose closely resembles d- fructose, but is dextro- rotatory, and as it is not readily fermented, can easily be obtained from i-fmctose, which is a syrup. Constitution of ^-Fructose. The general properties point to its ketonic structure, and this was further proved by Kiliani, who hydrolysed the cyanhydrin, and then reduced the hydroxy- acid thus obtained with hydriodic acid and phosphorus, and obtained methvl-butyl-acetic acid: /OH OH.CH 8 .(CH.OH) 3 .CO.CH 2 .OH OH.CH 2 .(CH.OH) 8 .C<-CN I NO-tljUli 312 XIV. CARBOHYDRATES Its configuration as Jiexanepentol-2-one f- + follows from its close relationship to ^-glucose. CHO CH 2 -OH d-Glucose, fl-C-OH rf-Fructose, CO HO-C-H HO-C-H H-C.OH H.C-OH H.C-OH H.C.OH CH 2 -OH CH 2 OH, since both yield the same osazone. Other stereo-isomeric ketohexoses are d-tagatose, obtained by the action of potassic hydroxide solution on d-galactose. It melts at 124, and yields the same osazone as d-galactose. d-Sorbose, obtained by oxidizing d-sorbitol; and /-sorbose, obtained as a by-product in the preparation of d-tagatose. Synthesis of Hexoses. 0. Loew obtained, by the action of lime-water on formaldehyde, a substance which he termed formose, C 6 H 12 6 , but which has since been shown to be a mixture of hexoses containing a-acrose. Butleroff has ob- tained a similar product from trioxymethylene. Fischer and Tafel (B. 1887, 20, 1093, 3384; 1889, 22, 97) obtained a mixture of sugars by the action of baryta water on glycerose (p. 306). Among these sugars was a-acrose, which is the starting-point for the synthesis of most other hexoses. The a-acrose is converted into its osazone; this is hydrolysed to the osone, and then reduced to the ketose, when d-Z-fructose is obtained. According to Neuberg (B. 1902, 35, 2626) the original a-acrose is d-Z-fructose, since it reacts with methyl- phenyl-hydrazine, yielding methyl-phenyl-fructosazone. The scheme (p. 313) gives a rtsumb of the steps involved in the synthesis of the other hexoses from a-acrose. The action of alkalis on hexoses has been studied by Lobry de Bruyn (B. 28, 3078), who has shown that glucose, mannose, and fructose are partially transformed into each other under the influence of dilute alkalis: Glucose ^= fructose ^z mannose. Fructose appears to be formed as an intermediate product in the conversion of glucose into mannose. The transfor- mation is only partial, and is accompanied by a change in rotatory power SYNTHESIS OF HEXOSES 311 -3 " S X I jli= *o_ """3 2 if I 31 4 XIV. CARBOHYDRATES B. Di- and Trisaeeharoses This group comprises those carbohydrates which may be regarded as derived from 2 or 3 molecules of a monose by the elimination of 1 or 2 mols. of water respectively. As such anhydrides, they are all readily hydrolysed when boiled with dilute acids, yielding monoses, usually hexoses. Thus cane-sugar yields a mixture of d-glucose and d-fructose; mal- tose yields ^-glucose only; milk-sugar yields ^-glucose and d-galactose : C 12 H 22 O n + H 2 = 2C 6 H 12 6 . Raffinose or melitriose is a type of a trisaccharose, and on hydrolysis yields melibiose and d-fructose. The hydrolysis in most of these cases can not only be effected by means of acids, but also by means of enzymes, e.g. diastase and invertase hydrolyse cane-sugar, maltase malt-sugar, &c. The disaccharoses are thus ethereal anhydrides of the hex- oses, e.g. cane-sugar is d-glucose-d-fructose anhydride, and malt- sugar d-glucose anhydride, &c. In this anhydride formation 8 of the original 10 OH groups have remained intact, as the bioses readily yield octacetyl derivatives: 2C 6 H r O(OH) 5 = [C 6 H 7 0(OH) 4 ] 2 + H 2 O. The compounds possess for the most part a sweet taste, and crystallize more readily and are more stable than the monoses, but resemble the latter in solubility. They are not directly fermentable, but are readily fermented after hydrolysis to monoses. All those which occur naturally are optically active. Cane-sugar does not reduce Fehling's solution, but milk- and malt-sugars do. Cane-sugar or Sucrose, SaccharoUose, C 12 H ?2 O n> occurs in red beet (Beta), in the sugar-cane (Saccharum), in the sugar-maple (Sorghum), and in many other plants, chiefly in the stem. Preparation. (a) From sugar-cane by expressing .the juice and evaporating it until crystallization begins. (&) From sugar-beet by a systematic extraction of the pulp with water, e.g. by the "diffusion process". The impure juice is then treated with lime ("defecation"), the excess of the latter thrown down by carbon dioxide ("saturation"), and the syrup filtered through animal charcoal, and evaporated in vacuo to crystallization. From the mother-liquid of molasses the crys- tallizable sugar still present can be obtained as the sparingly CANE-SUGAR, MILK-SUGAR, AND MALTOSE 315 soluble strontium saccharate, C 12 H 22 O n , SrO, which is then suspended in water and decomposed by carbon dioxide ("de- sugarizing of molasses"), Cane-sugar crystallizes in large monoclinic prisms, as is well seen in sugar-candy, and is soluble in one-third of its weight of water. It is not turned brown when heated with potash, and yields saccharates with lime and strontia, e.g. C 12 H. 2Z U + CaO + 2H 2 0; C 12 H 22 O n + 2CaO; C 12 H W U + 3CaO. Concen- trated sulphuric acid produces charring (difference from ^-glucose). Cane-sugar melts at 160, and remains in the amorphous condition for some time after cooling (barley- sugar); when heated more strongly, it becomes brown from the formation of caramel or sugar dye, and finally chars. The percentage of sugar in a solution of unknown strength can be determined from the specific rotatory power ([a] 2 D = 4-66-5) by measuring the angle (a) through which the plane of polarization is turned when a ray of polarized light is passed through a layer of the solution of known length (cf. p. 309). This is known as saccharimetry. It is readily hydrolysed by acids, and this process is com- monly spoken of as the inversion of cane-sugar, and the pro- duct as invert sugar. These names are due to the fact that the hydrolysis is accompanied by a change in the optical activity of the solution. The solution of cane-sugar is dextro- rotatory, but after hydrolysis (or inversion) it becomes laevo- rotatory, as ^-fructose is more strongly laevo- than d-glucose is dextro-rotatory. Sucrose itself does not reduce Fehling's solution, but after inversion readily reduces. This would indicate that in the anhydride formation the aldehydic group of ^-glucose and the ketonic group of ^fructose have been destroyed. The con- stitutional formula suggested by E. Fischer (B. 1893, 26, 2405) is: This formula readily accounts (a) for the formation of an -octacetyl derivative (m.-pt. 67); (b) for the absence of all reducing properties; (c) for the readiness with which it can be hydrolysed, since the two hexose molecules are united by means oi an atom of oxygen; (d) for the non-formation of a hydrazdrie. Milk-sugar or Lactose, Lactobiose, C 12 H 22 O n + H 2 0, occurs 316 XIV. CARBOHYDRATES in milk, and only occasionally in the vegetable kingdom. It is obtained by evaporating sweet whey. It crystallizes in hard rhombic prisms, and is much less sweet than cane-sugar, and also much less soluble in water. It is converted into " lacto- caramel" at 180. It shows muta-rotation (p. 309), and reduces Fehling's solution. Maltose or Malt-sugar, Maltobiose, C ]2 H 22 O n -f H 2 0, is formed by the action of diastase upon starch during the ger- mination of cereals (preparation of malt). It forms a hard white crystalline mass, very similar to grape-sugar, and strongly dextro-rotatory. It reduces Fehling's solution, but only to about two-thirds the extent to which ^-glucose does. Lactose and maltose resemble one another very closely, and are probably stereo-isomeric. Since they both possess reduc- ing properties, yield hydrazones, cyanhydrins, and can be oxidized to monobasic acids containing the same number of carbon atoms, it is obvious that they must contain an alde- hydo- group, and the following structural formula has been given to both by E. Fischer (B. 1893, 26, 2405): OH.CH 2 .CH(OH).CH.(CH.OH) 2 .CH.O.CH 2 .(CH.OH) 4 .CH:0 Raffinose or Melitriose, C 18 H 32 O 16 -f 5 !!./), is found in the sugar-beet, and therefore in molasses, in the manna of the eucalyptus, and in cotton-seed cake, &c. It is very like cane- sugar but tasteless, is strongly dextro-rotatory, and does not i'educe Fehling's solution. When inverted, it yields in the first instance d-fructose and "melibiose", the latter then breaking up into galactose and d-glucose. (For its constitution, see B. 1889, 22, 3118; also A. 232, 169.) Isomaltose is a biose obtained synthetically by Fischer (B. 1895, 28, 3024) by the condensing action of hydrochloric acid on glucose. It is non-fermentable. C. Polysaccharoses The empirical formula of the members of this series is CgHjQpg, but they all possess a much higher molecular weight, e.g. (CgHjoO,^. They are for the most part .amorphous and tasteless, insoluble in alcohol and ether; a few are soluble in cold water, but the majority not; thus cellulose is insoluble and also mucilage, the latter merely swelling up with water, while starch forms a jelly with hot water. When boiled with CELLULOSE 317 dilute acids or subjected to the action of enzymes, they are hydrolysed to mono- or di-saccharoses, generally to hexoses e.g. r C 6 H 10 (X + II = C 6 H 1? 6 . The formation of pentoses is frequently to be noticed in this decomposition. Like the foregoing compounds, therefore, the members of this group are to be regarded as the anhydrides of hexoses or pentoses. Consequently they still possess an alcoholic character and yield acetic and nitric esters, &c. Most of them are opti- cally active. With dilute nitric acid they yield the same oxida- tion products as are obtained from the corresponding hexoses or pentoses, and iodine frequently gives characteristic colora- tions. Cellulose, (CgH^O^, is widely distributed in nature as the membrane of plant cells; cotton, elder pith, wood, &c., consist of cellulose in a more or less pure state. It can be prepared by extracting cotton-wool or Swedish filter-paper with caustic potash, hydrochloric acid, water, alcohol, and ether succes- sively, or by treating pine wood with sulphuric and a little nitric acid. It forms a white amorphous powder, insoluble in the ordinary reagents, but soluble in an aminoniacal solution of cupric oxide, from which it is again thrown down by acids. When boiled with dilute sulphuric acid, it yields dextrine and d-glucose, while the concentrated acid converts it first into amyloid, an amorphous mass which is turned blue by iodine, and finally into dextrine. Parchment paper is simply unglazed paper which has been transformed superficially into amyloid by sulphuric acid. Many cellulose derivatives are compounds of commercial importance. The nitric esters, so called mtro-celluloses, are used for a variety of purposes, and are usually prepared by the action of a mixture of nitric and sulphuric acids on the carbohydrate. The nature of the product depends largely on the concentration of the acid mixture and upon the tempera- ture. In order to render the products stable, it is necessary to remove all traces of free acid. Collodion, a tetranitrate, is soluble in a mixture of alcohol and ether (1:7), and the solu- tion is largely used for coating materials and rendering them air-tight. It is also used for the manufacture of artificial silk and in photography. When mixed with camphor (various other substitutes, such as phenolic esters, are now used) it forms ordinary celluloid. Gun-cotton, pyroxiline, is probably a hexanitrate; in appearance it resembles cotton wool, but is not so soft. It burns readily and explodes when struck or 318 XIV. CARBOHYDRATES strongly heated. It is largely used for making smokeless powders, and is often met with in the form of compressed cakes. Practically all artificial silks are cellulose derivatives. The oldest method (Chardonnel) consisted in dissolving cellulose nitrates in a mixture of alcohol and ether (3:2), and forcing the solution under pressure from a copper vessel through small capillary tubes into water. The thread thus obtained was stretched to about the thickness of natural silk, and as it be- came hard was wound, dried, and denitrated by treatment with a reducing agent, such as ammonium sulphide or cuprous chloride and hydrochloric acid. Other methods which are now adopted consist in (a) the use of cellulose acetates obtained by the action of acetyl chloride and zinc acetate or quinoline, or of acetic anhydride and a mineral acid on cellulose. The solution of the acetate is squirted into alcohol through small holes, (b) The use of a solution of cellulose in ammoniacal cupric oxide, and forcing the solution through small holes into dilute acid (Thiele silk), (c) Use of viscose. Artificial, human, and horse hair are manu- factured by similar methods. The artificial silks are used for the manufacture of fabrics, and also for insulating metallic wires. Viscose (Cross and Bevari) is the sodium salt of cellu- lose xanthate. Cotton fibre is allowed to swell by treatment with sodium hydroxide solution, and is then shaken with car- bon disulphide. Its solution in water forms a gelatinous mass which can be moulded. When exposed to the air it shrinks and hardens to a horn-like mass. It is used as a substitute for glue, celluloid, horn, ivory, &c. When used for the manu- facture of artificial silk it is necessary to purify it; this is done by acidifying with a weak acid (acetic or lactic), precipitating with alcohol or brine, and washing. Viscoid is a mixture of viscose with clay or zinc oxide, and sets to an extremely hard mass. Starch or Amylum, (C 6 H 10 6 ) r , is present in all assimilating plants, being built up by the chlorophyll granules from the carbon dioxide absorbed, and is found especially in the nutri- ment reservoirs of the plants, e.g. in the grains of cereals, in perennial roots, potatoes, &c. It is converted into sugar during the transference of the sap. It forms a white velvety hygroscopic powder which consists of round or elongated granules built up of concentric layers, and insoluble in cold water. The interior of these granules consists of " granulose " GUMS AND DEXTRINES 319 and their husk probably of cellulose. When they are wanned with water, the latter is broken open and the granulose dis- solves; if the solution is moderately dilute, it can be filtered and a clear solution obtained, from which alcohol precipitates " soluble starch ". Both the granules of starch and its jelly are coloured an intense blue by iodine and bright yellow by bro- mine, from the formation of loose additive compounds, "iodide and bromide of starch ". The colour of the iodide of starch vanishes on heating, but reappears on cooling. Ordinary air- dried starch contains some 10-20 per cent of water, which can be removed by heating to 105. The so-called " soluble starch " is formed (a) when starch is heated with glycerol, (b) when starch is boiled with water con- taining sulphuric acid, (c) by the action of diastase or starch. Further treatment with acid converts it into dextrine and ^-glucose, and with diastase into dextrine and maltose and isomaltose (B. 1893, 26, 2533). Warming with very little dilute nitric acid to 110 yields dextrine. Lichenin, or Moss starch, present in many lichens, e.g. in Iceland moss (Cetraria islandica), is coloured a dirty blue by iodine; and inulin, present in the roots of the dahlia and many composites (Inula Helenium), is coloured yellow by iodine and converted into ^-fructose when boiled with water. Glycogen, or Animal starch, Liver starch, is present, e.g. in the livers of the mammalia. It is a colourless amorphous powder which is turned wine-red by iodine; after the death of the animal it rapidly changes into d-glucose, the same conversion being effected by boiling with dilute acids, while enzymes transform it into maltose. Dextrine, or Starch gum, is a comprehensive name applied to intermediate products obtained in the transformation of starch into maltose and d-glucose. It may be prepared (a) by heating starch either alone or with a little nitric acid, (b) together with d-glucose by boiling starch with dilute sulphuric acid, and (c) together with maltose by the action of diastase on starch. The dextrines are soluble in water, and are precipitated by alcohol. They are often named according to their reaction with iodine, e.g. amylo-dextrine blue, erythro-dextrine red, and achroo- dextrine no colour. They do not reduce Fehling's solution even when warmed, and are not directly fermentable by yeast but only after the prolonged action of diastase, glucose being formed as an intermediate product. Synthesis of Sugars. The sugars are extremely important 320 XIV. CARBOHYDRATES from the point of view of plant physiology. The plant ab- sorbs carbon dioxide and water, and with the aid of sunlight is capable, in the presence of chlorophyll, of transforming these into glucose and even more complex carbohydrates. Various speculations have been made with regard to the manner in which these complex compounds Are formed. Baeyer has sug- gested that the carbon dioxide is first reduced to formaldehyde, and this then polymerizes as in Loew's experiments, yielding carbohydrates, C0 2 H.C -> (H 2 C:0) 6 = C 6 H 12 O 6 . For many years the important link in this chain, viz. the reduction of carbon dioxide to formaldehyde, was missing; the reaction could not be accomplished in the laboratory. Fenton has recently shown (J. C. S. 1907, 91, 687) that when carbon dioxide is passed into water in which sticks of mag- nesium are immersed, a small amount of the gas is reduced to formaldehyde, especially in the presence of ammonia or phenyl- hydrazine. Lob has also found that moist carbon dioxide yields formaldehyde under the influence of the silent electric discharge (Zeit. Electrochemie,'1905, 11, 745; 1906, 12, 282). CLASS II CHEM18TE.Y OF THE CYCLIC COMPOUNDS XV. INTRODUCTION The compounds which have been treated of in Sections I to XIV are derivable from the homologous hydrocarbons C n H 2n+2 , C n H 2n , C n H 2n _ 2 , &c., by the exchange of hydrogen for halogen, hydroxyl or oxygen, amidogen, carboxyl, &c. ; and since all the hydrocarbons already mentioned may also be regarded as deri- vatives of methane (e.g. C 2 H 6 = CH 3 (CH 3 ) = methyl-methane, C 3 H 8 = CH 2 (CH 3 ) 2 = dimethyl-methane, C 2 H 4 = CH 2 :CH 2 = methylene-methane, C 2 H 2 = CHjCH = methine-methane, &c.), we may term the compounds which have been described in the foregoing portion of this book methane derivatives. As nearly all these compounds have open-chain formulae, they are spoken of as open- chain compounds, or often ali- phatic compounds. But in addition to this first class of organic compounds there is a second great class, viz. that of the closed-chain com- pounds. The old classification was into aliphatic or methane de- rivatives and aromatic or benzene derivatives. The expression "aromatic" is historical, but no longer justified by facts, since compounds of agreeable as well as unpleasant odour are to be found in both classes. The members of this second class which are derivable from the hydrocarbon benzene, C 6 H 6 (and also from more complicated hydrocarbons such as anthracene, naph- thalene, &c., which are themselves derivatives of benzene), just as the methane derivatives are from methane, are designated benzene derivatives. Eecent investigations have led to the discovery of numerous other cyclic compounds which cannot be regarded as simple derivatives of benzene, e.g. : CH CH:CH\ 7 (B480) 321 322 XVI. POLYMETHYLENE DERIVATIVES and hence the modern classification of the cyclic compounds is into: A. Carbocyclic or Isocyclic. In all these compounds the ring or closed chain is composed entirely of carbon atoms. The carbocyclic compounds are usually divided into (i) Polymethylene derivatives or naphthenes. (ii) Benzene derivatives or aromatic compounds, including the allied compounds naphthalene, anthracene, &c. B. Heterocyclic Compounds. In these compounds the closed ring is formed partly of carbon atoms and partly of atoms of other elements. Well-known examples are: CH:CH\ CH:CH\ >O (furane), >S (thiophene), mr.r<TT/ mr-mr/ V/JCL yy Ji- t^Ji . VyJd' \NH (pyrrole), CH<^SS;S5^N (pyridine), &c. vv-tL 1 Oxi.' CAKBOCYCLIC COMPOUNDS XVI. POLYMETHYLENE DERIVATIVES The hydrocarbons from which all these compounds are derived consist of three or more methylene groups united together to form a closed ring. The names for the specific hydrocarbons indicate the number of such groups, e.g. : 2 ^-tl-2 * ^-^-2 (trimethylene), | J_ (tetramethylene), /CH 2 2 ^nr PTT v. CH 2 < | (pentamethylene), CH 2 <X^ 2 ' 2NCH 2 (hexamethylene). x!H.CH ^L 2 'V,n 2 The systematic names for these compounds are cyclo-pro- pane, cyclo-butane, &c., although the compounds are isomeric with the defines, and have the same general formula, C n H2 n . The above names indicate the fact that the compounds are in a sense saturated. Eelative Stability of Polymethylene Compounds. It has been found that the majority of trimethylene derivatives are relatively unstable; to a certain extent they resemble ethylene. FORMATION OF POLYMETHYLENE COMPOUNDS 323 oxide, and are capable of forming additive products by the rupture of the ring. Thus bromine slowly transforms tri- methylene under the influence of sunlight into trimethylene dibromide : CK/ I . CH 2 Br.CH 2 .CH 2 Br. Tetramethylene derivatives are somewhat more stable, and penta- and hexa-methylene derivatives are remarkably stable and show little or no tendency towards the rupture of the molecule. These facts are in harmony with Ba&yer's tension theory. If the four valencies of the tetravalent carbon atom are assumed to be symmetrically distributed in space around the carbon atom, it is found that ring formation in the case of a / 2 compound CH 2 <\ | can only take place by the exercise of CH 2 a considerable strain in the molecule; hence when the ring formation is completed there is considerable tendency for it to spring apart or rupture at some point. With penta- and hexa- methylene compounds, on the other hand, it can be seen by the aid of models that practically no strain is required to com- plete the ring formation, and thus the rings when once formed are relatively stable. GENERAL METHODS OF FORMATION 1. By the action of sodium on dihalogen derivatives of the paraffins (Freund). The two halogen atoms must not be attached to the same or to adjacent carbon atoms. CH 2 .CH 2 Br CH 2 .CH 2 + 2Na = 2NaBr + I CH 2 -CH 2 Br 2. Acids and their esters can be obtained by the conden- sation of ethyl sodio-malonate with ethylene dibromide and other dihalogen derivatives (W. H. Perkin, Jun.): fNa 2 C(C0 2 Et) 2 = 324 XVI. POLYMETHYLENE DERIVATIVES and the ester on hydrolysis yields trimethylene-dicarboxylic acid. Ethyl acetoacetate may be substituted for ethyl malonate. 3. By the action of halogens (bromine, or preferably iodine) on the sodio-derivatives of certain esters, e.g. sodio-derivative of ethyl butane-tetracarboxylate (W. H. Perkin, Jun.): CH 2 .CNa<C0 2 Et) 2 CH 2 -C(CO 2 Et) 2 CH 2 .CNa(C0 2 Et) 2 2 * CH 2 .C(CO 2 Et) 2 . 4. By intramolecular pinacone formation. Just as ketones on reduction yield pinacones : (CH3) 2 .C:0 , (CH 3 ) 2 .C:0 + - (cf. p. 191), so certain diketones on reduction yield cyclic pinacones, i.e. dihydric alcohols derived from the polymethy- lene hydrocarbons: H.CO.CH 3 H xCH 2 .C(OH).CH 3 O.CH 3 + ' H2 \CH 2 .C(OH).CH 3 1 : 2-Dimethyl-l : 2-dihydroxy cyclo-pentane. 5. A number of ketones derived from the polymethylenes have been obtained by the dry distillation of the calcium salts of the higher dibasic acids of the oxalic series (/. Wislicenus\ e.g. calcium adipate yields keto-pentamethylene : CH 2 CH 2 CO O\ CH 2 CH ; . CH 2 .CH 2 .CO.O> = Ca and this can be reduced to pentamethylene. The constitution of the keto-derivative follows from the fact that on oxidation the ring is ruptured and glutaric acid is formed. Keto-hexamethylene and keto-heptamethylene or suberone have been obtained by similar methods, but the yield is not so good in these two cases. 6. Hexamethylene compounds are often obtained by the reduction of benzene derivatives with sodium and alcohol: General Properties. On the whole these compounds some- what closely resemble the paraffins as regards their chemical ISOMERISM OF POLYMETHYLENE COMPOUNDS 325 properties, hence the names cyclo-pentane for pentamethylene, cyclo-hexane, &c. The trimethylene compounds, however, resemble the de- fines, e.g. (a) they can combine with bromine to form additive compounds; (b) they are slowly oxidized by permanganate. In neither of these reactions do they take part so readily as ;iae simpler olefines, and in all cases the products obtained are formed at the expense of the rupture of the ring. The fact that the majority of the hydrocarbons of this series resemble paraffins indicates that the formation of a closed chain does not affect to any considerable extent the properties of a compound (cf. Benzene). In their chemical properties the compounds closely resemble the corresponding derivatives of the paraffins, e.g. the acids resemble to a large extent the fatty acids, yielding salts, esters, acid chlorides, amides, &c. Isomerism. (a) Position Isomerism. No examples of iso- merism have been met with in the case of mono-substituted de- rivatives, e.g. only one tetramethylenecarboxylic acid is known. Position isomerism can occur in the case of di- and poly-sub- stituted derivatives, e.g. tetramethylene-1 :l-dicarboxylic acid and isomeric 1 : 2 and 1 : 3 acids. 4 ' l:2-Dicarboxylic acid l:l-Dicarboxylic acid COoH-C ^V^-LJ-2' l:3-Dicarboxylic acid. The number of isomerides possible in each case can be worked out by the student (cf. Benzene Derivatives). (b) Stereo -isomerism. Certain di- substituted derivatives have been found to exist in isomeric forms which are struc- turally identical. These must therefore be stereo-isomeric. Some of the simplest examples of this stereo-isomerism are met with in the dibasic acids. For example: Tetramethylene-l:2-dicarboxylic acid exists in two isomeric forms. In both acids the 2C0 2 H groups are Attached to the carbon atoms 1 and 2, and the only difference is in the relative spatial relationships of the groups. If the plane of the paper represents the plane in which the centres of gravity of 326 XVI. POLYMETHYLKNE DERIVATIVES the four carbon atoms of the ring lie, then the possibilities are H C0 2 H (I) cis. (I) That the two C0 2 H groups lie in the same plane either above or below the plane of the paper (this is known as the tis acid) ; and (II) that the two C0 2 H groups lie in different planes, one above and one below the plane of the paper (this is known as the trans acid). As a rule, the cis acids yield inner f^O anhydrides, e.g. C 4 H 6 <^QQ^>0, more readily than the stereo- isomeric trans acids, and the cis acids are generally transformed into the corresponding trans acids when heated with hydro- chloric acid at 190. (Cf. Perkin, Jun., J. C. S. 1894, 572.) A simple method of depicting these isomerides is due to Aschan (B. 1902, 35, 3389). The plane of the carbon atoms of the ring is represented by a straight line. The unsubstituted hydrogen atoms are not denoted, only those which have been replaced by sub- stituents. It has been found that the symmetry of such pro- jections corresponds with the symmetry of the molecules projected. For the cis dicarboxylic acids, for example, if C0 2 H = X, we have: X_* and ^_ _^ (I) cis. (H) trans. (III). The cis compound (I) is not perfectly asymmetric, whereas the trans compound (II) is. Corresponding with (II) is a third isomeride, which stands in the same relationship to (II) as an object to its mirror image, or as d- to Z-lactic acids. Both should therefore be optically active (one d and the other I to the same extent), and should be capable of combining to yield a racemic compound. All the trans compounds prepared arti- ficially are optically inactive, and are presumably therefore racemic compounds of (II) and (III), although so far very few have been resolved into optically active components. fcENZENE DERIVATIVES 32^ Intermediate between the polymethylene compounds and benzene derivatives are the reduction products of benzene and its derivatives, e.g. di- and tetra-hydrobenzene, tetrahydro- phthalic acid, &c., C 6 H 8 , C 6 H 10 , C 6 H 8 (C0 2 H) 2 . These will be discussed along with the benzene compounds," from which they are derived. XVII. BENZENE DERIVATIVES. INTRODUCTION Benzene is, as its formula C 6 H 6 shows, a compound much poorer in hydrogen than the paraffins, containing 8 hydrogen atoms less than hexane, C 6 H J4 ; in the same way all benzene derivatives are much poorer in hydrogen, i.e. richer in carbon than the analogous methane derivatives, as is seen by com- paring e.g. benzoic acid, C r H 6 2 , with heptoic acid, C 7 H 14 2 , or aniline, C 6 H 7 N, with ethylamine, G 2 H 7 N, &c. The hydrogen atoms of benzene are, like those of methane, replaceable by numerous types of radicals. By the entrance of halogens, halide substitution products are formed, by the entrance of NH 2 , aromatic bases, of OH, phenols, of N0 2 , nitro-compounds, and of CH 3 , &c., the homologues of benzene; there are, in addition to these, aromatic alcohols, aldehydes, acids, &c. These benzene derivatives are partly analogous in their properties to the methane derivatives of corresponding com- position; in part, however, they show new and peculiar pro- perties of their own (see pp. 328 et seq.). One distinguishes between mono-, di-, tri-, &c., substituted benzene derivatives according as 1, 2, or more hydrogen atoms are replaced by the various radicals; thus, for instance, toluene, C 6 H 5 CH 3 , and chloro-benzene, C 6 H 5 -C1, are mono-derivatives, dimethyl- benzene, C,H 4 (CH 3 ) 2 , and dichloro-benzene, C 6 H 4 C1 2 , di-deri- vatives, and so on. It is not necessary that the substituents should be identical, so that innumerable compounds are known containing various substituents, e.g. OHC 6 H 4 -N0 2 , nitro- Shenol; C 6 H 4 BrS0 3 H, bromobenzene-sulphonic acid; CH 3 6 H 3 (NO 2 ) 2 , dinitro-toluene. Such compounds have usually some of the characteristics of all those mono-derivatives which result from benzene by the exchange of one hydrogen atom for one of these substituents. All the derivatives of benzene can be converted either into benzene itself or into very closely allied compounds by rcla- 326 XVI. POLYMETHYLENE DERIVATIVES the four carbon atoms of the ring lie, then the possibilities are H (I) cis. (I) That the two C0 2 H groups lie in the same plane either above or below the plane of the paper (this is known as the cis acid); and (II) that the two C0 2 H groups lie in different planes, one above and one below the plane of the paper (this is known as the trans acid). As a rule, the cis acids yield inner anhydrides, e.g. C 4 H 6 <^pQ^>0, more readily than the stereo- isomeric trans acids, and the cis acids are generally transformed into the corresponding trans acids when heated w r ith hydro- chloric acid at 190. (Cf. Perkin, Jun., J. C. S. 1894, 572.) A simple method of depicting these isomerides is due to Aschan (B. 1902, 35, 3389). The plane of the carbon atoms of the ring is represented by a straight line. The unsubstituted hydrogen atoms are not denoted, only those which have been replaced by sub- stituents. It has been found that the symmetry of such pro- jections corresponds with the symmetry of the molecules projected. For the cis dicarboxylic acids, for example, if C0 2 H = X, we have: ^^ and ^_ __* (I) cis. (II) trans. (III). The cis compound (I) is not perfectly asymmetric, whereas the trans compound (II) is. Corresponding with (II) is a third isomeride, which stands in the same relationship to (II) as an object to its mirror image, or as d- to /-lactic acids. Both should therefore be optically active (one d and the other / to the same extent), and should be capable of combining to yield a racemic compound. All the trans compounds prepared arti- ficially are optically inactive, and are presumably therefore racemic compounds of (II) and (III), although so far very few have been resolved into optically active components. 6ENZENE DERIVATIVES 32 1 Intermediate between the polymethylene compounds and benzene derivatives are the reduction products of benzene and its derivatives, e.g. di- and tetra-hydrobenzene, tetrahydro- phthalic acid, &c, C 6 H 8 , C 6 H 10 , C 6 H 8 (C0 2 H) 2 . These will be discussed along with the benzene compounds, from which they are derived. XVII. BENZENE DERIVATIVES. INTRODUCTION Benzene is, as its formula C 6 H 6 shows, a compound much poorer in hydrogen than the paraffins, containing 8 hydrogen atoms less than hexane, C 6 H J4 ; in the same way all benzene derivatives are much poorer in hydrogen, i.e. richer in carbon than the analogous methane derivatives, as is seen by com- paring e.g. benzoic acid, C r H 6 2 , with heptoic acid, C 7 H 14 2 , or aniline, C 6 H 7 N, with ethylamine, C 2 H r N, &c. The hydrogen atoms of benzene are, like those of methane, replaceable by numerous types of radicals. By the entrance of halogens, halide substitution products are formed, by the entrance of NH 2 , aromatic bases, of OH, phenols, of N0 2 , nitro-compounds, and of CH 3 , &c., the homologues of benzene; there are, in addition to these, aromatic alcohols, aldehydes, acids, &c. These benzene derivatives are partly analogous in their properties to the methane derivatives of corresponding com- position; in part, however, they show new and peculiar pro- perties of their own (see pp. 328 et seq.). One distinguishes between mono-, di-, tri-, &c., substituted benzene derivatives according as 1, 2, or more hydrogen atoms are replaced by the various radicals; thus, for instance, toluene, C 6 H 5 'CH 3 , and chloro-benzene, C 6 H 5 -C1, are mono-derivatives, dimethyl- benzene, C,H 4 (CH 3 ) 2 , and dichloro-benzene, C 6 H 4 C1 2 , di-deri- vatives, and so on. It is not necessary that the substituents should be identical, so that innumerable compounds are known containing various substituents, e.g. OH .C 6 H 4 -NO 2 , nitro- phenol; C 6 H 4 BrS0 3 H, bromobenzene-sulphonic acid; CH 3 . C 6 H 3 (N0 2 ) 2 , dinitro-toluene. Such compounds have usually some of the characteristics of all those mono-derivatives which result from benzene by the exchange of one hydrogen atom for one of these substituents. All the derivatives of benzene can be converted either into benzene itself or into very closely allied compounds by rela- 328 XVII. BENZENE DERIVATIVES. INTRODUCTION lively simple reactions. Thus all the carboxylic acids of ben- zene (benzoic, phthalic, mellitic, &c.) yield benzene on dis- tillation with lime, while other acids, such as salicylic, evolve C0 2 and yield phenol; the last-named compound is converted into benzene when distilled with zinc dust. The homologues of benzene are converted by oxidation into benzene-carboxylic acids, which yield benzene when heated with lime. The relationship of a benzene derivative to its mother substance is therefore a very simple one. This circumstance is one particularly worthy of note, since the atomic group C 6 H 6 is already a tolerably complicated molecule in itself, and also because benzene cannot by any means be transformed into a simpler hydrocarbon containing 5, 4, or 3 carbon atoms; when oxidized, which is a matter of difficulty, it yields carbonic or similar simple organic acids. The benzene derivatives are connected with one another by the most varied reactions. The N0 2 group is readily con- vertible into NH 2 , and the latter is replaceable by halogen, hydrogen, and hydroxyl; the halogen is also replaceable by methyl, carboxyl, &c. As a rule, the group of 6 carbons with the hydrogens is spoken of as the benzene nucleus, and all substituents are spoken of as side chains. Thus in C 6 H 5 -CHO, C 6 H 4 *(CH 3 ) 2 , C 6 H 5 NH 2 the radicals underlined are the side chains. o CHARACTERISTIC PROPERTIES OF BENZENE DERIVATIVES In many chemical properties benzene and its derivatives differ markedly from the paraffins or unsaturated open-chain hydrocarbons. 1. The aromatic hydrocarbons and their derivatives are readily attacked by concentrated nitric acid, yielding nitro- derivatives : Certain of the higher paraffins also yield nitro-derivatives when heated with nitric acid (p. 95). 2. Sulphonic acids are readily formed by the action of con- centrated or fuming sulphuric acid : 2 .OH = H 2 + C C H 5 .S0 2 .OH. This type of reaction is never met with in the aliphatic series. tSOMERISM OF BENZEKE DERIVATIVES 329 3. The homologues of benzene differ from the paraffins especially as regards oxidation; while the latter are only attacked with difficulty by oxidizing agents, the former are readily converted into benzene-carboxylic acids: C 6 H 5 .CH 3 C 6 H 6 .C0 2 H. 4. The halogens chlorine and bromine can react with ben- zene in two distinct ways : (a) yielding substituted derivatives, e.g. C^Hg + Br 2 = C 6 H 5 Br + HBr, or (b) yielding additive products, e.g. C 6 H 6 Br 6 . The process of substitution is the more important and the commoner of the two reactions. 5. There are not wanting other distinguishing characteristics between the aromatic hydrocarbons and the paraffins. Thus the halogen compounds C 6 H 5 X are chemically less active, and the hydroxyl compounds, e.g. C 6 H 5 (OH), are of a more acidic nature than the corresponding fatty bodies. The phenyl radical, C 6 H 5 , is therefore more acid or " negative " in character than the ethyl, C 2 H 5 (cf. V. Meyer, B. 20, 534, 2944; A. 250, 118). 6. Diazo-compounds are far more common in the aromatic series than in the aliphatic. ISOMERIC RELATIONS 1. While several isomeric mono-derivatives are both theo- retically possible and have been actually obtained from each hexane, CgH^, benzene is only capable of forming a single mono -derivative in each case; isomeric mono -derivatives of benzene are unknown. The six hydrogen atoms of benzene thus possess an equal value, or are similarly situated within the molecule. This is not merely an empirical law, but one which has been proved experimentally. PROOF OF THE EQUAL VALUE OF THE SIX HYDROGEN ATOMS Let the 6 H atoms be designated as a, b, c, d, e, and / respectively. (1) Phenol, C 6 H 5 (OH), whose hydroxyl may have replaced the H atom a, may be converted into bromo-benzene, C 6 H 5 Br, and this latter into benzoic acid, C 6 H 5 (C0 2 H). The carboxyl in the latter has therefore also the position a, i.e. it has re- placed the H atom a. 330 XVII. BENZENE DERIVATIVES. INTRODUCTION (2) Three hydroxy-benzoic acids, C 6 H 4 (OH)(C0 2 H), can either be prepared from benzoic acid or converted into it; their carboxyl therefore has the position a, and consequently their hydroxyl must replace some one of the other H atoms, be it 5, c, or d. (3) Each hydroxy-benzoic acid can be decomposed, yielding carbon dioxide and ordinary phenol, C 6 H 6 OH: C 6 H 4 (OH)(C0 2 H) = C 6 H 5 (OH) + C0 2 . And since the latter compound contains the hydroxyl in position a, according to (1), while the hydroxyl in the hy- droxy-benzoic acids replaces the H atoms b, c, and d, it follows that the hydrogen atoms a, b, c, and d are of equal value. (4) Now, as will be explained on p. 331, for each H atom there are present two other pairs of symmetrical hydrogen atoms, i.e. pairs of which either the one or the other atom may be replaced by any given radical without different sub- stances resulting. But the atoms of such a pair cannot both be present in the positions a, b, c, and d, as in this case three hydroxy-benzoic acids could not exist. It must therefore be the remaining H atoms e and / which are respectively in posi- tions symmetrically situated to two of the former, and which are therefore of equal value with them, i.e. e = c, f = b. Since, however, a = b = c = d, it follows that all the 6 hydrogen atoms are of equal value (Ladenburg, B. 7, 1684). 2. With di-substituted derivatives of benzene it has been found that in each case three distinct isomeric forms exist. The two substituents may be alike, or they may be dis- similar, e.g. three dichloro-benzenes, C 6 H 4 C1 2 , three diamino- benzenes, C 6 H 4 (NH 2 ) 2 , three dimethyl-benzenes, C 6 H 4 (CH 3 ) 2 , three hydroxy-benzoic acids, C 6 H 4 (OH)(C0 2 H), are known. In no case have more than three such isomerides been found. It can be shown that with respect to each H atom of ben- zene, e.g. for a, two pairs of other H atoms, e.g. b and /, c and e, are symmetrically situated, so that it makes no difference whether, after a is replaced, the second substituent replaces the one or the other of the symmetrically placed hydrogen atoms, say b or /. According to the above notation, there- fore, ab = af t and ac = ae. On the other hand, the com- binations ab and ac are not equivalent, but represent isomers; the combination ad, the only remaining case, represents the third isomer. CONSTITUTION OF BENZENE 331 PROOFS THAT FOR EVERY H ATOM (a) TWO OTHER PAIRS OF SYMMETRICALLY LINKED H ATOMS EXIST 1. According to Hubner and Petermann (A. 149, 129; cf. also Hubner, A. 222, 67, 166), the (so-called meta-) bromo- benzoic acid, which is obtained by brominating benzoic acid, and whose Br atom may be in position c and C0 2 H in posi- tion a, yields with nitric acid two nitrobromo-benzoic acids, C 6 H 3 Br(N0 2 )(C0 2 H), the N0 2 being, say, in positions b and/. These are both reduced by nascent hydrogen to the same (so- called ortho-) amino-benzoic acid, C 6 H 4 (NH 2 )(C0 2 H), the N0 2 being here changed to NH 2 and the Br replaced by H. Since the same amino-benzoic acid is formed in both cases, notwith- standing that the nitro-groups must be in the place of different H atoms, say b and /, from the fact of the two nitro-acids being dissimilar, it follows that b and / must be arranged sym- metrically as regards the H atom a, i.e. ab af. 2. In an analogous manner salicylic acid, C 6 H 4 (OH)(C0 2 H), which can be prepared from the above-mentioned amino-ben- zoic acid, yields two nitro-derivatives, C 6 H 3 (OH)(N0 2 )(C0 2 H). If, however, the hydroxyl in these is replaced by hydrogen (a reaction which can be effected by indirect methods), the nitro- benzoic acids thus obtained, C 6 H 4 (N0 2 )(G0 2 H), are identical, and therefore the H atoms which have been replaced by N0 2 are in position^ symmetrical to a. When this nitro- benzoic acid is in its turn reduced to amino-benzoic acid, C 6 H 4 (NH 2 )(C0 2 H), it is not the above (ortho-) amino-acid (where ab = af) which is obtained, but an isomer. The N0 2 groups cannot therefore here be in the positions b and /, but must replace two other H atoms which are likewise symmetric towards a, say c and e, i.e. ac ae (Hubner, A. 195, 4). Thus two pairs of H atoms are symmetrically situated as regards the H atom a: ab = afj ac = ae. There remains only the third possible combination ad] the sixth H atom d is situated towards the first a in a position of its own, i.e. in one to which there is no corresponding position. For further particulars, cf. Ladenburg, "Theorie der aromat. Verbindungen ", Braunschweig, 1876; WroUewsky, A. 168, 153; 192, 196; B. 8, 573; 9, 1055; 18, Ref. 148. Noelling, B. 1904, 37, 1015, gives a very simple proof. It has been assumed in the considerations just detailed that when one compound is converted into another by tho 332 XVII. BENZENE DERIVATIVES. INTRODUCTION exchange of atoms or radicals (NH 2 for N0 2 , H for OH), this exchange is effected without a so-called " molecular rearrange- ment" taking place at the same time (see p. 132). Experience has proved that this may be taken for granted in a large number of reactions which proceed with relative smoothness and at comparatively low temperatures. Those instances in which a molecular rearrangement ensues are now well known ; especially is this the case in the fusion of sulphonic acids with potash (exchange of S0 3 H for OH), a reaction which takes place at relatively high temperatures only, and which frequently leads to isomers of the compounds expected. In other reactions which occur at high temperatures a rearrange- ment of the atoms in the molecule can also take place. Thus, when potassium ortho-hydroxy-benzoate is heated to 220, the potassium salt of the para-acid is formed; the three isomeric bromo-benzene-sulphonic acids, C 6 H 4 Br(S0 3 H), and the three bromo-phenols, C 6 H 4 Br(OH), yield only meta-dihydroxy -benzene (resorcinol), C 6 H 4 (OH) 2 , when fused with potash, and not the three isomeric dihydroxy -benzenes; ortho- phenol -sulphonic acid, C 6 H 4 (OH)S0 3 H, yields the para-acid when heated. Re- actions of this nature probably arise from the successive taking up and splitting off of atoms or atomic groups. CONSTITUTION OF BENZENE The formula C 6 H 6 at once indicates that benzene cannot be a saturated open-chain compound. The possibility that it is an open-chain unsaturated compound containing several double or triple bonds has been shown to be untenable, e.g. dipro- pargyl (p. 53), CH:C.CH 2 .CH 2 .CiCH, although resembling benzene in physical properties, is quite different as regards most of its chemical properties; it combines readily with bro- mine, yielding additive compounds with 2, 4, 6, or 8 atoms of bromine, and it is also oxidized with the greatest readiness. Benzene combines with bromine only slowly and under specific conditions, and then yields C 6 H 6 Br 6 ; it is, further, extremely stable towards oxidizing agents. The equivalency of the 6 hydrogen atoms in the benzene molecule is a further strong argument against such open-chain formulae. KehiU was the first to suggest a closed -chain, cyclic, or ring formula for benzene. In order to account for the existence of only one mono- substituted derivative, C 6 H 6 X, but of three isomeric di-sub ISOMERISM OF BENZENE DERIVATIVES 333 stituted derivatives, C^H^Xg, it is necessary to assume that a single hydrogen atom is attached to each carbon atom. CH This formula is usually known as the benzene ring. In the above formula the six hydrogen atoms are symmetri- cally placed with respect to one another, and thus in the for- mation of a mono-substituted derivative it is immaterial which one of the six hydrogens is replaced; only one compound, C 6 H 5 X, can be formed. With di-substituted derivatives three isomerides are theo- retically possible, viz.: the 1:2 or ortho-compound, 1:3 or meta-compound, and the 1:4 or para-compound. The compound 1:5 is identical with 1:3, and 1:6 is identical with 1:2. Cf. JPohl, B. 1910, 43, 3474. The hydrogen atoms in positions 2 : 6 form one pair of sym- metrical hydrogen atoms mentioned on p. 329, and those in positions 3:5 form the second pair, whereas the hydrogen in position 4 has no other hydrogen atom corresponding with it. Similarly, three tri-substituted derivatives, C 6 H 3 X 3 , are known, and only three are possible with such a ring formula, viz. : XXX (III) (I) 1:2:3 or adjacent tri-derivative. (II) 1 : 3 : 5 or sym. tri-derivative. (III) 1:2:4 or unsym. tri-derivative. Any other combination is identical with one of these, 2:4:6 = 1:3:5, and 1:4:6 = 1:2:4. 334 XVII. BENZENE DERIVATIVES. INTRODUCTION The number of isomerides is considerably increased when the three substituents are not similar, e.g. in a compound, ith a tetra-substituted derivative, C 6 H 2 X 4 , where all four substituents are alike, only three isomerides are possible, namely those corresponding with the 0-, m-, and |?-di-deriva- tives : X And with a penta-substituted derivative, C 6 HX 5 , only one form is possible. The number of isomerides actually found in each case is in perfect harmony with these theoretical deductions. The ring formula for benzene, given above, represents each carbon atom as tervalent; the difficulty of accounting for the fourth valency can be overcome in several ways. The first method, suggested by KeJcuU, was to suppose alternate double and single bonds between the 6 carbon atoms, e.g.: CH This formula is in perfect harmony with the formation of benzene from acetylene, and of trimethyl-benzene from acetone. It also largely accounts for the formation of additive com pounds by benzene and its derivatives, e.g. : CH* CHC1 1 Hdl H H( HC1 Dihydro-benzeue Tetrahydro-benzene Benzene hexachloride. Two arguments which have been brought forward against this formula are CONSTITUTION OF BENZENE 335 (a) Two ortho-disubstituted derivatives should be possible, namely, those represented by the formulae: In formula (I) the 2 carbon atoms to which the substituents are attached are united by a double bond, and in formula (II) by a single bond. KekuU has suggested that the single and double bonds may be continually changing, so that positions 2 and 6 are really symmetrical with respect to 1. (b) The stability of benzene towards oxidizing agents has been used as an argument against such a formula containing three double bonds in the molecule. Di- and tetrahydro- benzenes obtained by the reduction of benzene which con- tain respectively two and one double bonds in their molecules, are readily oxidized, and also readily yield additive compounds with halogens. It has been suggested that the peculiar sym- metrical structure of the benzene molecule may account for its stability. (II) A second method of accounting for the fourth valency of each carbon atom is that first suggested by Armstrong, and afterwards developed by Baeyer: (IlA) It represents the fourth valency of each carbon atom as directed towards the centre of the molecule, where the 6 are kept in equilibrium. This centric formula for benzene repre- sents a method of linking which is unknown in the fatty series. When reduced to dihydro-benzene, four of the six centric bonds form two double bonds. 336 XVII. BENZENE DERIVATIVES. INTRODUCTION This readily accounts for the great difference between the chemical properties of benzene and of its reduction products. Various other formulae have been suggested for benzene, e.g. Ladenburg's prism formula, Claus's diagonal formula, and Dewar's formula. (in) (IV) (V) Dewar Claus A strong objection to the prism formula and to any other three-dimension space formula is that the molecules of certain substituted derivatives would be perfectly asymmetric, and should therefore exist in optically active modifications. No benzene derivative which occurs naturally is optically active, and attempts to resolve substituted benzene derivatives, e.g. C 6 H(OH)(C0 2 H)(CH 3 )(C 3 H 7 )(N0 2 ), nitrothymotic acid, have been unsuccessful. Rugheimer (B. 1896, 29, 1967) states, however, that he has obtained w-methyl-jp-hydroxy-benzoic acid in an optically active form. Other objections to the prism formula are (a) the difficulty of accounting for the reduction products of benzene, and (b) the fact that when benzene is oxidized by various methods no compound is met with which contains a carbon atom attached to 3 other carbon atoms, as is the case in the prism formula. Researches upon the constitution of benzene and its deriva- tives by Baeyer (A. 245, 251, 256, 258, 269, 176), and upon similar (and also nitrogen) ring-systems by Bamberger (A. 257, 1), have shown that the nature of the groups entering the benzene molecule has an influence upon the special (fourth) linking of the atoms ; so that the constitution of the ring in all benzene derivatives is not to be taken as established without further investigation because a particular formula applicable to benzene itself has been arrived at. On the contrary, KeTcaU's formula (I) might suit for certain compounds (as has been proved by Biwyer for phloroglucinol [B. 24, 2687]), and formula (IL\) for others. Compare also A. 274, 331; 279, 1; B. 30, 2975; A. 306. 125; Kauffmann, Ahren's Sammlung, 1907, 12, 79. ISOMERISM OF BENZENE DERIVATIVES 337 METHODS FOR DETERMINING WHICH OF THREE ISO- MERIC COMPOUNDS IS THE ORTHO, WHICH MET A, AND WHICH PARA. 1. A method worked out by Korner (1875) for the three dibromobenzenes. One of these (a) is a solid melting at 89; a second (b) is a liquid which boils at 224, and when solidified melts at 1; and the third (c) is a liquid boiling at 219 and melting at +1. When further brominated, the compound a yields only one tribromobenzene; compound b, under similar conditions, yields a mixture of two isomeric tribromobenzenes; and compound c a mixture of three. Br Br Br From a glance at the above formulae, it is obvious (1) that the para- or l:4-compound could give rise to only one tri- bromobenzene, (2) that the ortho- or l:2-compound could give a mixture of two isomeric tribromobenzenes, and (3) that the meta- or l:3-compound could give a mixture of three isomeric tribromobenzenes. The compound melting at 89 is therefore ^-dibromobenzene, the one boiling at 224 is the ortho-, and the one boiling at 219 and melting at +1 is the meta-compound. Incidentally, this gives us a method for determining which of the three tribromobenzenes is the adj., which the sym., and which the unsym. A glance at the formulae indicates that the sym.-tribromobenzene is the one which is formed from the m-dibromobenzene only. The adj. is the one formed from both ortho- and meta-, and the unsym. is the one which is formed from ortho-, meta-, and para-dibromobenzenes. Similar results are obtained by examining the nitro-dibromo- benzenes obtained by nitrating the dibromobenzenes. The p-compound yields only one nitre-derivative; the 0-com- (B480) Y 338 XVII. BENZENE DERIVATIVES. INTRODUCTION pound yields two nitro-derivatives; the ra-compound yields three nitro-derivatives : Br but the nitro-dibromobenzenes thus formed are all different. Similar methods may be adopted for determining the constitutions of the three diamino-benzenes, C 6 H 4 (NH 2 ) 2 , by determining from how many of the six diamino-benzoic acids each of the three can be obtained by elimination of carbon dioxide. The m-compound is the one which is formed from three distinct acids, the ortho- from two, and the para- from one only (Griess). The relationships between the three xylenes, C 6 H 4 (CH 3 ) 2 , and the six nitro -xylenes are exactly analogous to those between the three dibromobenzenes and their six nitro-deri- vatives. 2. When the constitution of several groups of compounds, e.g. the dibromobenzenes, the xylenes, and the diamino-ben- zenes have been settled, then the constitutions of other com- pounds can be determined by conversion into one of the compounds of known constitution, e.g. the dinitro-benzene which yields m-diamino-benzene on reduction is the m-dinitro- compound, or the acid obtained by the oxidation of o-xylene must be the 0-dicarboxylic acid. This constitution is confirmed by the fact that this acid is the only one of the three ibomeric benzene-dicarboxylic ISOMERISM OF BENZENE DERIVATIVES 339 acids which yields an inner anhydride, phthalic anhydride, ), and hence the two C0 2 H groups are probably attached to two adjacent carbon atoms. 3. The constitution of certain di-substituted derivatives is based on Ladenburg's proof (A. 179, 174) of the equivalence of the three unsubstituted hydrogen atoms in mesitylene, C 6 H 3 (CH 3 ) 3 ; in other words, on the fact that mesitylene is sym.-trimethyl-benzene, e.g. the constitution of w-xylene is based on the following reactions: GEL C0 2 Ladenburg's proof is briefly as follows : Mesitylene yields a dinitro-derivative, C 6 H(CH 3 ) 3 (N0 2 ) 2 , in which two of the three nucleus hydrogen atoms (a and b) are replaced by nitro-groups. From this we get, by the three processes of reduction, acety lation, and nitration, a dinitro-acetamino-mesitylene : C 6 H(CH 3 ) 3 (N0 2 )(NH 2 ) C 6 H(CH 3 ) 3 (N0 2 )(NHAc) a b C 6 (CH 3 ) 3 (N0 2 ) 2 (NHAc), in which the third hydrogen (c) is replaced by N0 2 ; on hydro- lysis, this yields C 6 (CH 3 ) 3 (N0 2 ) 2 (NH 2 ), and on elimination of the amino-group, C 6 H(CH 3 ) 3 (N0 2 ) 2 , a olinitro-mesitylene, which is identical with the original dinitro-compound started with. Hence two of the hydrogen atoms (say b and c) are similarly situated. The nitro-amino-mesitylene, C 6 H(CH 3 ) 3 (N0 2 )(NH 2 ), a ' b in which the nitro-group is in position a and the amino- in position b t yields C 6 H 2 (CH 3 ) 3 N0 2 , and this, when reduced, a acety lated, nitrated, and hydrolysed: C 6 H 2 (CH 3 ) 3 NH 2 C 6 H 2 (CH 3 ) 3 .NHAc a a & or c a 6 or c a nitro-amino-mesitylene which is identical with the original nitro-amino-mesitylene, and hence the position a is similarly situated to either b or c, but in the first part of the argument it was shown that b = c, .*. a = b = c. 340 XVII. BENZENE DERIVATIVES. INTRODUCTION Other Types of Isomerism. 1. In addition to the cases of isomerism dealt with in the preceding pages (isomerism due to the positions of the substituents in the nucleus), other types of isomerides are met with. A frequent example is the isomerism of a compound containing a substituent in the nucleus with a compound containing the same substituent in the side chain; well-known examples are C 6 H 4 C1 CH 3 and C 6 H 5 CH 2 C1, and C 6 H 5 -CH 2 .NH 2 . Isomerism of this type is usually accompanied by considerable difference in chemical properties. 2. " Side-chain isomerism " is the name given when the iso- merism is confined to the side chain, e.g. : C 6 H 6 .CH 2 .CH 2 .CH 3 and C 6 H 5 .CH(CH 3 ) 2 Normal- and Isopropyl-benzene. Stereo-isomerism. When the side chain contains an asym- metric carbon atom, e.g. C 6 H 5 CH(OH)(C0 2 H), mandelic acid, stereo-isomerism of the type of the active lactic acids is met with. Stereo-isomerism of the type of the crotonic acids is met with in unsaturated compounds like cinnamic acid, C 6 H 5 CH:CHC0 2 H, and stereo-isomerism analogous to that de- scribed in the case of polymethylene derivatives is met with among the reduced benzene derivatives, e.g. di-, tetra-, and hexahydrophthalic acid (p. 466). OCCURRENCE OF THE BENZENE DERIVATIVES Many benzene derivatives occur in nature, e.g. oil of bitter almonds, benzoic acid, salicylic acid, and hippuric acid, while others are obtained from the destructive distillation of organic substances, especially of coal. The destructive distillation of coal yields (a) gases (illumi- nating gas); (b) an aqueous distillate containing ammonia and its salts, &c.; (c) tar; and (d) coke. The various fractions obtained by distilling coal-tar contain : (a) Fatty hydrocarbons in small amount. (b) Aromatic hydrocarbons, the most important of which are the following: Benzene, C 6 H 6 , toluene, CgH^CHg, and many homologues of benzene containing methyl substituents, e.g. mesitylene, C 6 H 3 (CH 3 ) 3 , durene and isodurene, C 6 H 2 (CH 3 ) 4 . More complex hydrocarbons : cinnamene, C 6 H 5 CH : CH 2 ; naphthalene, C 10 H 8 ; diphenyl, C 12 H 10 ; acenaphthene, C 12 H 10 ; FORMATION OF BENZENE DERIVATIVES 341 fluorene, C 13 H 10 ; anthracene, C 14 H 10 ; phenanthrene, C U H 10 ; pyrene, C 16 H 10 ; chrysene, C 18 H 12 . (c) Other neutral substances, e.g. alcohol (in very small quantity), benzonitrile, cumarone, CgHgO. (d) Phenols: e.g. phenol or carbolic acid, C 6 H 5 OH; o-, m-, and ^>-cresol, CH 3 C 6 H 4 OH. (e) Bases: pyrrole, C 4 H 5 N; pyridine, C 5 H 5 N, and its homo- logues; aniline, CgH 5 NH 2 ; quinoline, C 9 H 7 N, and its homo- logues; acridine, C 13 H 9 N. (See Schultz, "Chemie des Stein- kohlentheers ", Braunschweig, 1886.) All these compounds are not present in the original coal, but are formed during the process of distillation. The compounds formed, and also their relative amounts, depend on numerous factors, e.g. nature of coal, temperature and pressure of distil- lation, kind of retort used, &c. The presence of the hexahydro-compounds of benzene and its homologues has been proved in most natural petroleums, especially in those from the Caucasus (J. pr. Ch. (2) 45, 561; cf. p. 41). FORMATION OF BENZENE DERIVATIVES FROM OPEN-CHAIN COMPOUNDS The benzene derivatives can be produced from the fatty compounds by a relatively small number of reactions only. 1. Many methane derivatives, e.g. alcohol, yield a mixture containing a large number of the derivatives of benzene when their vapours are led through red-hot tubes. Acetylene, C 2 H 2 , polymerizes at a low red heat to benzene, C 6 H 6 (Berthelot): CH CH HC CH HC CH HC CH HC CH V In an analogous manner allylena CH 3 'C':CH, yields mesity- lene or 1:3:5 trimethyl-benzene, C 6 H 3 (CH 3 ) 3 , when distilled with dilute sulphuric acid, while crotonylene, CH 3 C:CCH 3 , yields hexamethyl -benzene, C 6 (CH 3 ) 6 ; bromo- acetylene and iodo-acetylene polymerize to s-tribromo- and ^tn-iodo-benzene when exposed to light; propiolic acid, CH*:C'C0 2 H, poly- merizes to trimesic acid, C 6 H 3 (C0 2 H) 3 . 342 XVII. BENZENE DERIVATIVES. INTRODUCTION 2. Ketones condense to benzene hydrocarbons when dis- tilled with dilute sulphuric acid, e.g. acetone yields mesitylene (Kane, 1838) and methylethyl ketone, triethyl-benzene: CH 3 CH 3 C(C C (H 2 )CH CH(H) 2 HC CH | -* I' 1 +3H 2 0. CH 3 .C(0) 0(0). CH 3 CH 3 -C CJ.CH 3 (H 2 )CH C 3 mols. Acetone H Mesitylene 3. Certain 1 : 2-diketones, aldehyde acids, and keto-aldehydes are transformed in an analogous manner into benzene deri- vatives by suitable "condensing" agents; diacetyl, CH 3 CO'CO'CH 3 , is transformed by alkalis into xylo-quinone, C 6 H 2 2 (CH 3 ) 2 (B. 21, 1411), and ethyl /3-hydroxyacrylate into the ethyl ester of trimesic acid (B. 20, 2930). 4. Certain 1 : 5 diketones react with hydrochloric acid, yield- ing reduced benzene derivatives, which can readily be trans- formed into benzene derivatives, e.g. ethylidene-diacetoacetic ester (from acetaldehyde and acetoacetic ester) yields dimethyl- QQ QTT cyclo-hexenone, CH<Tr<\T XtrOOHMe, the dibromide of ^L/ivie-urig which is converted into sym.-xylenol, (Knoevenagel). 5. By the action of methylene iodide upon the sodium com- pound of ethyl pentane-tetracarboxylate and subsequent hy- drolysis, hexahydro-isophthalic acid is formed (W. H. Perkln, jun., J. C. S. 1891, 59, 798): CH 9 CH, 2 C CH.' H 2 C C(C0 2 Et) 2 H 2 C CH-C0 2 H | \ N +CH 2 I 2 | | H 2 C Na 1 H 2 C CH 2 )(C0 2 Et) 2 CH.C0 2 H Sodium compound of ethyl Hexahydro-isophthalic pentane-tetracarboxylate acid. 6.' By the action of sodium upon ethyl succinate (Herrmann, A. 211, 306; B. 16, 1411), or upon ethyl bromo-acetoacetate (Duisberg), ethyl snccinylo- succinate, "ethyl diketo-hexa- DECOMPOSITION Of BENZENE COMPOUNDS 343 methylene-dicarboxylate ", is obtained, and is readily trans- formed into ethyl dihydroxy-terephthalate and then into quinol: EtO;CO CO CO 2 Et.HC;H j CH 2 C0 2 Et-HC CH 2 H 2 C i H;CH.CO 2 Et H 2 C CH'COaEt COiOEt CO 2 mols. Ethyl succinate Ethyl succinylo-succinate. 7. When ethyl sodio-malonate, CHNa(C0 2 Et) 2 , is heated, ethyl phloroglucinol-dicarboxylate is formed, and this on hy- drolysis yields phloroglucinol. (Cf. p. 420.) 8. Hexyl iodide, C 6 H 13 I, is converted into hexachloro-ben- zene, C 6 C1 6 , when heated with IC1 3 , and into hexabromo-ben- zene, C 6 Br 6 , by bromine at 260; the latter compound can also be obtained by heating CBr, to 300. 9. Mellitic acid, C 6 (C0 2 H) 6 , is produced by the oxidation of graphite or lignite by means of KMnO 4 . 10. Potassium carboxide, which is formed by the action of carbon monoxide upon potassium, is the potassium compound of hexahydroxy-benzene, C 6 (OH) 6 . THE CONVERSE TRANSFORMATION OF BENZENE DERI- VATIVES INTO FATTY COMPOUNDS 1. When the vapour of benzene is passed through a red-hot tube it is partially decomposed into acetylene. 2. Benzene is oxidized by chloric acid to " trichloro-pheno- malic acid", i.e. /3-trichloraceto-acrylic acid, CC1 8 'COCH: CH.C0 2 H (KekuU and Strecker, A. 223, 170). When chlorine is allowed to act upon phenol in alkaline solution, the benzene ring is broken, and the acids, C 6 H 6 CloO 4 , C 6 H 5 C10 4 , &c., are produced (Hantzsch, B. 20, 2780). Catechol, resorcinol, and phloroglucinol are also ultimately converted into fatty compounds by treatment with chlorine and the sub- sequent action of alkalis, e.g. resorcinol (m-dihydroxybenzene) yields dichloro-maleic acid (B. 1894, 27, 3364). Bromine, acting upon bromanilic acid, yields perbromo-acetone, CBr 8 COCBr 3 . 3. Nitrous acid converts catechol into dihydroxy-tartaric acid (see p. 260), while permanganate of potash, acting upon phenol, gives rise to inactive tartaric acid and oxalic acid (Dobner, B. 24, 1753). 344 XVIII. BENZENE HYDROCARBONS 4. Oxidizing agents which are capable of rupturing the benzene ring yield, as a rule, carbonic, formic, and acetic acids. 5. The hexahydro- benzenes are transformed into hydro- carbons of the methane series when heated with hydriodic acid at 280 (Berthelot, A. 278, 88; 302, 5). This decom- position appears, however, to be very difficult of accomplish- ment. 6. When reduced with metallic sodium and amyl alcohol, 0-hydroxy-benzoic acid is converted into pimelic acid: CH XVIII. BENZENE HYDROCARBONS A. Homologues of Benzene, The benzene hydrocarbons are for the most part colourless liquids, insoluble in water, but readily soluble in alcohol and ether (durene and penta- and hexamethyl-benzenes are crys- talline). They distil without decomposition, possess a peculiar and sometimes pleasant ethereal odour, and burn with a very smoky flame. Many, especially benzene and its methyl deriva- tives, occur in the lower fractions from coal-tar; others are prepared synthetically by Fittig's or Friedel-Crafts' methods. Modes of Formation. 1. Fittig's Synthesis. By treating a mixture of a brominated benzene hydrocarbon and an alkyl iodide or bromide with sodium in the presence of dry ether (A. 131, 303): Br + CH 3 I +2Na == C 6 H 6 .CH 3 -f Nal + NaBr; 66 3 == 66 . 3 - a r; C 6 H 4 Br(0 2 H 5 ) + C 2 H 6 I + 2Na = C 6 H 4 (C 2 H 5 ) 2 -f Nal + NaBr. BENZENE AND ITS HOMOLOGUES 345 346 XVIII. BENZENE HYDROCARBONS Jannasch synthesised ^?-xylene, durene, and isodurene by this method. 2. Friedel^ and Crafts 1 Synthesis (1877). By the action of alkyl chlorides (bromides or iodides) on aromatic hydro- carbons in the presence of anhydrous aluminic chloride, (A1C1 3 ): C 6 H 6 + CH 3 C1 = C 6 H 6 .CH 3 +HC1; C fl H 6 + 2CH 3 C1 = C 6 H 4 (CH 3 ) 2 + 2HC1, &c. This reaction is, like the preceding one, capable of very wide application; by means of it all the hydrogen atoms in benzene can be gradually replaced by methyl. The best yields are often obtained by the addition of carbon bisulphide, which serves as a diluent, and also prevents the temperature rising to any appreciable extent, and thus largely avoids the decomposing or differentiating action of the chloride on the homologues first formed. At higher temperatures, for ex- ample, C 6 H 5 'CH 3 would be transformed to a large extent into C 6 H 6 and C 6 H 4 (CH 3 ) 2 (B. 1894, 27, 1606, 3235). Zinc and ferric chlorides (Nencki, B. 1899, 32, 2414) act in the same way as chloride of aluminium, while ethyl chloride and other haloid compounds, such as chloroform and acid chlorides, may replace methyl chloride. (See respectively triphenyl-methane and the ketones; cf. also B. 14, 2624; 16, 1744; Ann. de chim. et phys. [6] \ 419; B. 30, 1766.) The metallic chloride forms additive compounds with the acyl chloride or alkyl derivative, e.g. CEL COC1, A1C1 3 , and also with the condensation product, e.g. C 6 H 5 CO CH 3 , A1C1 3 (Per- rier, B. 1900, 33, 815). The reaction is a unimolecular one, except when an excess of A1C1 3 is used. For a summary of the Friedel- Crafts' reaction, see Steele, J. C. S. 1903, 1470. Alcohols also, like their haloid esters, are capable of react- ing in an analogous manner in presence of ZnCl 2 : C 6 H 6 + C 4 H 9 OH = C 6 H 6 .C 4 H 9 + H 2 O. 3. A method of formation somewhat analogous to the Fittig synthesis is the action of alkyl iodides or methyl sulphate on organo-magnesium haloids (Grignard's compounds) in toluene solution (Houben, B. 1903, 36, 3083; 1904, 37, 488; Werner, ibid., 2116, 3618): CH 3 .C 6 H 4 .MgBr + C 2 H 6 Br = CH 3 .C 6 H 4 .C 2 H 6 + MgBr 2 . FORMATION Of BENZENE HYDROCARBONS 347 4. The benzene hydrocarbons are formed when their carb- oxylic acids are distilled with soda-lime: C 6 H 5 .C0 2 H = C 6 H 6 + C0 2 ; CH 3 .C 6 H 4 .C0 2 H = C 6 H 6 6 .CH 3 4-00 2 . 5. From sulphonic acids (p. 402) by the elimination of the S0 3 H group: C 6 H 3 (CH 3 ) 2 S0 3 H + H 2 = C 6 H 4 (CH 3 ) 2 -t-H 2 S0 4 . This reaction can be effected by dry distillation, by heating with concentrated hydrochloric acid to 180, by distillation of the ammonium salt (Caro), or by treatment with superheated steam, e.g., in presence of concentrated sulphuric acid (Arm- strong, W. Kelbe); also by heating with concentrated phosphoric acid (B. 22, Kef. 577). 6. From the amino-compounds by transforming these into diazonium-compounds (p. 387), and boiling the latter with ab- solute alcohol or with an alkali stannite solution (B. 22, 587). Griess reaction. 7. By distillation of the phenols (or ketones) with zinc dust. homers and Constitution. The table given on p. 345 shows that the benzene hydrocarbons, from C 8 H 10 on, exist in many isomeric modifications; thus, isomeric with the three xylenes we have ethyl-benzene, with the three trimethyl-benzenes the three methylethyl-benzenes and the two propyl-benzenes, with durene, isodurene, cymene, &c. The constitution of these hydrocarbons follows very simply from their modes of formation. A hydrocarbon C ]0 H 14 , for instance, which is obtained from benzene and methyl chloride by the Friedel-Crafts' reaction, can only be a tetramethyl-ben- zene; another of the same molecular formula C 10 H 14 , which has been prepared from bromo-benzene, butyl bromide and sodium, must be a butyl-benzene ; while a third, from j9-bromo-toluene, normal propyl iodide and sodium, must be a jp-propyl-toluene (p-methyl-7i-propyl-benzene), &c. The synthesis therefore de- termines the constitution. The groups CH 3 , C 2 H 5 , &c., which replace hydrogen in benzene, are termed "side chains". When oxidized, the hydrocarbons yield a benzene-mono-, di-, or tri-, <fec., carboxylic acid, e.g. benzoic acid, C 6 H 5 C0 2 H, 0-, m-, >-phthalic acid, C 6 H 4 (C0 2 H) 2 , according to the number of side chains present in the hydrocarbon; and a further proof of the constitution of the compound is thus afforded. 348 XVIII. BENZENE HYDROCARBONS If, for example, a hydrocarbon C 9 H 12 yields a benzene-tri- carboxylic acid, C 6 H 3 (C0 2 H) 3 , upon oxidation, it must contain three side chains, i.e. must be a trimethyl-benzene; should a phthalic acid, on the other hand, result, then it can only be an ethyl-toluene. Since cymene yields p- (or tere-) phthalic acid, C 6 H 4 (C0 2 H) 2 , on oxidation, its two side chains must be in the ^-position towards one another. The respective isomers resemble each other closely in physical properties, their boiling-points, for example, lying very near together. The ortho-derivatives often boil at about 5, and the meta- at about 1 higher than the para-compounds; the boiling-point rises with an increasing number of methyl groups. (Of. B. 19, 2513.) Behaviour. 1. The benzene hydrocarbons are, as a rule, readily nitrated and sulphonated, mono-, di-, and even tri- derivatives being all usually capable of preparation, according to the conditions. As a rule, it is only the hydrogen atoms of the benzene nucleus which are replaced, the side chains reacting as paraffin residues. Hexamethyl-benzene can thus neither be nitrated nor sulphonated. Exceptions to this generalization are met with, e.g. mesitylene yields a nitro- derivative, C 6 H 3 (CH 3 ) 2 .CH 2 .N0 2 . 2. Oxidation. Benzene itself is not readily oxidized; per- manganate of potash converts it slowly into formic and oxalic acids, some benzoic acid and phthalic acid being produced at the same time. These doubtless result from some previously formed diphenyl. The homologues of benzene, on the other hand, are readily oxidized to carboxylic acids, the benzene nucleus remaining unaltered, and each side chain no matter how many carbon atoms it may contain being converted, as a rule, into carb- oxyl. Nitric acid allows of a successive and often a partial oxi- dation of individual side chains, chromic acid mixture (K 2 Cr 2 7 + H 2 S0 4 ) acts more energetically, converting all the side chains in the p- and m-compounds into carboxyl, and completely destroying the o-compounds. The latter may be oxidized to the corresponding carboxylic acids by KMn0 4 . When a hydrocarbon is selectively oxidized, the longest side chain, as a rule, is most readily oxidized; thus C 3 H 7 C 6 H 4 - CH 3 yields first C0 2 H . C 6 H 4 . CH 3 , and then C 6 H 4 (C0 2 H) 2 . 3. Reduction. The benzene hydrocarbons and most of their derivatives are capable of taking up six atoms of hydrogen. REDUCED BENZENE DERIVATIVES 349 Benzene itself is only converted into hexahydro-benzene, C 6 H 12 , with difficulty, but toluene, xylene, and mesitylene combine with hydrogen more easily when they are heated with phos- phonium iodide, PH 4 I, at a rather high temperature, the com- pounds C 7 H 8 H 2 , C 8 H 10 H 4 , and C 9 H 12 H 6 being formed. The two former can then be made to take up more hydrogen by energetic reaction. An interesting method of formation of C 6 H 12 is by the action of freshly reduced nickel on a mixture of hydrogen and ben- zene or its homologues at moderate temperatures. Hexahydro-benzene and its analogues, C^H^, are colourless liquids insoluble in water, and of somewhat lower boiling-point than their mother compounds, into which they can be readily retransformed by oxidation, either by heating with sulphur or by means of fuming nitric acid, nitration also taking place in the latter case; e.g. hexahydro-benzene yields nitro-derivatives of benzene. They are found in petroleum, especially in that from the Caucasus (Eeilstein, Kurbatow), and differ from the isomeric defines by being insoluble in sulphuric acid, and by not forming additive products with bromine (cf. B. 20, 1850; A. 234, 89; 301, 154). They are identical with hexamethylene and its derivatives, and react as saturated compounds. The partially reduced benzene derivatives, on the other hand, behave more like olefines. The dihydro-benzenes, C 6 H 8 , readily combine with two or four atoms of bromine, and are readily oxidized by alkaline permanganate, as .might be inferred from the presence of double bonds in the molecule. Two isomeric compounds, A 1 : 3-dihydro-benzene and A 1 : 4-dihydro-benzene, are known: L 2 Cyclohexa-1 : 4-diene Tetrahydro-benzene, , which exists in one form H 2 k/H 2 H 2 Cyclohexene 350 XVIII. BENZENE HYDROCARBONS only, is readily oxidized, combines with two atoms of chlorine and bromine or with a molecule of hypochlorous acid. All are colourless, volatile liquids. 4. Behaviour with Halogens. Chlorine and bromine react differently, according to the conditions. In direct sunlight they yield with benzene the additive products C 6 H 6 C1 6 and C 6 H 6 Br 6 , while in diffused daylight, especially in presence of a little iodine, SbCl 3 or MoCl 5 , they give rise to the substitution products C 6 H 5 C1, C 6 H 6 Br, &c. (For further details, and for substitution by iodine, see pp. 57 and 356.) 5. Chromium oxychloride, Cr0 2 Cl 2 , converts the methylated benzene hydrocarbons into aromatic aldehydes (p. 423; cf. B. 23, 1070). (Etard's reaction.) 6. The numerous " condensations " which benzene, &c., can undergo with oxygenated compounds in presence of ZnCl 2 , P 4 10 , or H 2 S0 4 , and with chlorinated compounds in presence of A1C1 3 , are of great interest; thus benzene yields diphenyl- ethane with aldehyde and sulphuric acid, and benzophenone with benzoic acid and phosphorus pentoxide. 7. In presence of aluminic chloride, oxygen can be intro- duced into benzene, yielding phenol; sulphur, yielding phenyl sulphide; ethylene, yielding ethyl-benzene; carbon dioxide, yielding benzoic acid. Benzene, C 6 H 6 , was discovered by Faraday in 1825, and detected in coal-tar by Hofmann in 1845. It is obtained from the portion of coal-tar which boils at 80-85 by fractionating or freezing. It may be prepared chemically pure by distilling a mixture of benzoic acid and lime. The ordinary benzene of commerce usually contains thiophene, and thus gives a char- acteristic deep-blue coloration when shaken with a solution of isatin in concentrated sulphuric acid; but it may be freed from the impurity by repeated shaking with small quantities of sulphuric acid, which converts the thiophene into a sulphonic acid. It burns with a luminous smoky flame, and is a good solvent for resins, fats, iodine, sulphur, phosphorus, &c. When its vapour is led through a red-hot tube, diphenyl is obtained. C 7 H 8 . Toluene, C 6 H 5 -CH 3 . Discovered in 1837. Formation: by the dry distillation of balsam of Tolu and of many resins. Synthesis according to Fittig (see above). Preparation-, from coal-tar, in which it is found accompanied by thio-tolene. Toluene is very similar to benzene. It boils at 110, and is still liquid at 28. Cr0 2 Cl 2 converts it into benzaldehyde, and HN0 3 or Cr0 8 into benzoic acid. XYLENES 351 C 8 H 10 . (a) o-, m-, and ^-Dimethyl-benzenes or Xylenes, C 6 H 4 (CH 3 ) 2 . The xylene of coal-tar consists of a mixture of the three isomers, m-xylene being present to the extent of 70 to 85 per cent. These cannot be separated from one another by fractional distillation. wi-Xylene is more slowly oxidized by dilute nitric acid than its isomers, and can thus be obtained with relative ease. For the separation of these isomers by means of H 2 S0 4 see B. 10, 1010; 14, 2625; 17, 444; 25, Kef. 315; and for their recognition see B. 19, 2513. Benzene and toluene yield chiefly ortho-, together with a little para-xylene, when subjected to the Friedel-Crafts synthesis (B. 14, 2627). 1. o- Xylene, which can be prepared synthetically from 0-bromo-toluene, methyl iodide, and sodium, is oxidized to carbonic acid by chromic acid mixture, and to 0-toluic acid, C 6 H 4 (CH 3 )C0 2 H, by dilute nitric acid; it is difficult to nitrate. 2. m-Xylene or iso-xylene can also be prepared from mesity- lene, C 6 H 3 (CH 3 ) 3 , [1:3:5], by oxidation to mesitylenic acid, CgH 3 (CH 3 ) 2 C0 2 H, and subsequent distillation with lime. Dilute nitric acid only oxidizes it at a temperature of 120, while chromic acid mixture converts it into isophthalic acid, C 6 H 4 (C0 2 H) 2 . It yields tetra- and hexahydro- derivatives, C 8 H 14 and C 8 H 16 ; the latter is present in Caucasian petroleum, and boils at 11 9. 3. ^-Xylene is prepared from j?-bromo-toluene, or better, ;?-dibromo-benzene, methyl iodide, and sodium (B. 10, 1356; B. 17, 444). M.-pt. 13. Dilute nitric acid oxidizes it to 0-toluic acid, C,H 4 ( GIL )C0 2 H, and terephthalic acid, C 6 H 4 (C0 2 H) 2 . Dihydro-^-xylene can be prepared from ethyl succinylo-suc- cinate. Liquid; b.-pt. 133. It has an odour of turpentine, and is closely related to the terpenes. (Cf. Baeyer, B. 25, 2122.) Jb) Ethyl-benzene, C 6 H 5 .0 2 H 5 , is obtained from C 6 H 5 Br CoH 5 Br by the Fittig reaction; from cinnamene, CJ3 5 CH:CH 2 , on reduction with HI; and from C 6 H 6 and C 2 H 5 C1 by the Friedel-Crafts reaction. It is found in small quantity in the xylene from tar, and when oxidized yields benzoic acid. C 9 H 12 . (a) Trimethyl-benzenes, 1. Mesitylene, l:3:5-tfn- methyl-benzene, C 6 H 3 (CH 3 ) 3 . This is contained in coal-tar along with the two other isomeric trimethyl-benzenes ("tar- cumene "), and can be synthesised from acetone or allylene. It is a liquid of agreeable odour. Nitric acid oxidizes the 352 XVIII. BENZENE HYDROCARBONS side chains one by one, while chromic acid mixture decom- poses it completely. (For constitution, see p. 339.) 2. Pseudo-cumene, l-.Z-A-trimethyl-benzene, is separated from mesitylene, not by fractional distillation, but by taking ad- vantage of the sparing solubility of pseudo-cumene-sulphonic acid (B. 9, 258). Its constitution follows from its formation from bromo-j^-xylene [1:4:2], and also from bromo-w-xylene [1:3:4], by the Fittig reaction. Nitric acid oxidizes the side chains successively. 3. Hemellithene, l:2:3-trimethyll)enzene (see B. 15, 1853), is present in coal-tar (B. 20, 903). (b) Pr opyl- benzenes, 1. w-Propyl- benzene, C 6 H 5 .CH 2 - CH 2 'CH 3 , is obtained from bromo-benzene and normal propyl iodide by the Fittig reaction, and also from benzyl chloride, C 6 H 5 .CH 2 C1, and zinc ethyl. 2. Isopropyl-benzene or Cumene, CgH 5 CH(CH 3 ) 2 , is pro- duced by the distillation of cumic acid, C 6 H 4 (C 3 Hf)(C0 2 H), with lime; from benzene and iso- or normal propyl iodide by means of A1C1 3 , in the latter case with molecular rearrange- ment (p. 132); and from benzylidene chloride, C 6 HCHC1 2 , and zinc methyl, this last method furnishing proof of its con- stitution. On oxidation, both n- and iso-compounds yield ben- zoic acid. Cj H 14 . (a) Durene, 1:2:4:5- or s-tetramethyl-benzene, C 6 H 2 (CH 3 ) 4 , has been found in coal-tar, and can be prepared from toluene and methyl chloride by the Friedel-Crafts reaction, or from dibromo-m-xylene (from coal-tar xylene), methyl iodide, and sodium (A. 216, 200). It is a solid, and possesses a camphor- like odour. (For its constitution see B. 11, 31.) Both of its isomers are known. (b) Methyl-propyl-benzenes, C 6 H 4 (CH 3 )C 3 H 7 . The most important of these is cymene or isopropyl-p-methyl-benzene. It is found in Eoman cummin oil (Cuminum cyminum), in eucalyptus oil, &c., and is formed when camphor is heated with PgSg, or better, P 4 10 , also when oil of turpentine is heated with iodine, &c. It has been synthetically prepared from ^7-bromo-isopropyl-benzene, methyl iodide, and sodium; and also from j9-bromo-toluene, n-propyl iodide, and sodium, the %-propyl- changing here into the isopropyl group. It is a liquid of agreeable odour. Cymene was formerly regarded as 7i0maZ-propyl-^>-methyl- benzene, but its synthesis from ^?-brom-w0-propyl-benzene, methyl iodide, and sodium established its constitution as an UNSATURATED BENZENE HYDROCARBONS 353 isopropyl derivative (cf. JVidman, B. 24, 439). When oxidized, it yields either ^7-toluic acid, terephthalic acid, cumic acid, or />-tolyl-methyl-ketone, according to the conditions. C 12 H 18 . Hexamethyl- benzene, Mellitene, C 6 (CH 3 ) 6 , crys- tallizes in prisms or plates which melt at 164. It can neither be sulphonated nor nitrated (see p. 347). KMn0 4 oxidizes it to mellitic acid, C 6 (C0 2 H) 6 . B. Unsaturated Benzene Hydrocarbons The benzene hydrocarbons containing less hydrogen comport themselves, on the one hand, like benzene itself, and on the other like the un saturated hydrocarbons of the fatty series, combining readily with hydrogen, halogen, halogen hydride, &c. They are derived from the olefines or acetylenes by the exchange of H for C 6 H 5 , thus: C 6 H 5 'CH:CH 2 , cinnamene, styrene, or phenyl-ethylene; C 6 H 5 .C|CH, phenyl-acetylene. They are formed by the elimination of C0 2 from the corre- sponding acids, by the elimination of HBr from compounds of the type C 6 H 5 CH 2 CH 2 Br, and by the elimination of water from certain secondary and tertiary alcohols (C. R. 1901, 132, 1182). Cinnamene, C 6 H 5 -CH:CH 2 , occurs along with other com- pounds in storax (Styrax officinalis), in the juice of the bark of Liquidambar orientate, and in coal-tar (being in this last case probably a degradation product of certain acids). It is formed when cinnamic acid is slowly distilled or heated with water to 200 (B. 1890, 23, 3269): C 6 H 5 CH : CH :COO;H. It is also obtained when benzene vapour and ethylene are passed through a red-hot tube, or when a-bromo-ethyl-benzene, C 6 H 5 'CH 2 'CH 2 Br (by action of bromine on ethyl-benzene), is heated. It is a liquid, has a characteristic odour, and boils at 140. It changes on keeping into the polymeric meta-styrene, an amorphous transparent mass, and yields ethyl-benzene when heated with hydriodic acid. Addition of HBr converts it into a-bromo-ethyl-benzene, C 6 H 5 CH 2 CH 2 Br. By the conden- sation of styrene with toluene, in presence of concentrated sulphuric acid, and on subsequent superheating, anthracene is formed (Kramer, Spilker, B. 23, 3169). Phenyl-acetylene, CyHg.CjCH, is produced by the separa- tion of C0 2 from phenyl-propiolic acid. It is a pleasant-smelling liquid boiling at 142, and as an acetylene derivative yields white and pale-yellow explosive (B4SO) Z 354 XIX. HALOGEN DERIVATIVES metallic compounds with solutions of silver and cuprous oxides. It combines with water to aceto-phenone, C 6 H 6 CO CH 3 , when it is dissolved in sulphuric acid, and the solution is diluted with water, or when heated with water to 300. XIX. HALOGEN DERIVATIVES SUMMAKY Cl Br I M.-p. B.-p. M.-p. B.-p. M.-p. B.-p. C 6 H 6 C1 ............... -45 132 -31 157 -30 188 C 6 H 4 C1 2 o ......... liq. 179 -1 224 +27 286 m ......... liq. 172 liq. 220 +40 285 p ......... +56 173 +87 219 +129 285 CH 3 .C fl H 4 Clo ... 34 159 -26 181 liq. 211 m ... 48 162 40 184 liq. 204 p ... +7'4 162 28 185' +35 211'5 C 6 H 6 .CH 2 C1 ........ -48 175 ... 198 +24 decomposes C 6 Cl 6 (Br 6 ,I fl ) ....... 229 326 Benzene and its homologues can give rise to (A) additive compounds with bromine or chlorine, or (B) substituted deri- vatives. A. Additive Compounds These are of comparatively little importance, and are formed when the hydrocarbon is exposed for some time to chlorine or bromine vapour in bright sunlight. Benzene hexachloride, C 6 H 6 C1 6 , exists in two stereo-isomeric modifications; the one melts at 157, and the other sublimes at 310. When warmed with alkali, they yield trichloro-benzene and HC1. The isomerism is probably due to the different arrangement of the halogen atoms on either side of the plane of the benzene ring in the two compounds. The hexabromide (Matthews, J. C. S. 1901, 79, 43) melts at 212. B. Substituted Derivatives Haloid substitution products in immense number are derived from the benzene hydrocarbons by the exchange of hydrogen for halogen. They are either colourless mobile liquids or SUBSTITUTED HALOGEN DERIVATIVES 855 crystalline solids, insoluble in water but readily soluble in alcohol and ether, distil unchanged, and are distinguished by their peculiar odour and also, in part, by their irritant action upon the mucous membrane. They are heavier than water. The substitution products of benzene and its homologues may be arranged in two distinct groups. In one the halogen is bound very firmly, far more so than in methyl chloride, ethyl iodide, &c.; it cannot be exchanged for OH (by means of AgOH), or for NH 2 (by NH 3 ), &c., but reacts with sodium (see the Fittig reaction, p. 344) ; A. 332, 38 ; for an exception, see B. 1892, 25, 1499; 1895, 28, 2312; and magnesium (see below). All the substituted derivatives of benzene and many common derivatives of its homologues belong to this class. In the second group, of which benzyl chloride is a good type, the halogen atoms enter into reaction as readily as do those of the haloid substitution products of the methane series. When the members of the first group are subjected to oxi- dation, a process which converts side chains into carboxylic groups, chloro-derivatives of benzoic and other acids are ob- tained. The members of the second group, when subjected to similar treatment, yield aromatic acids which are free from halogen, e.g. benzoic acid, C 6 H 5 C0 2 H, phthalic acid, C 6 H 4 (C0 2 H) 2 . From this it follows that the halogen is present in the first case in the benzene nucleus, and in the second in the side chain. Chloro-toluene is C 6 H 4 C1CH 3 , and benzyl chloride C 6 H 5 .CH 2 C1. When the halogen atoms replace hydrogen atoms of the benzene nucleus, the products are extremely stable, and the halogen cannot readily be removed from the molecule. On the other hand, when the halogen replaces hydrogen atoms of a side chain (methyl or ethyl groups), the compound is ex- tremely reactive, and closely resembles the halogen derivatives of the fatty series. In this way it is always easy to arrive at the constitution of a compound from the behaviour of its halogen atoms and from its products of oxidation. Thus a compound C 7 H 6 C1 2 , which yields monochloro-benzoic acid upon oxidation, has manifestly the formula C 6 H 4 C1 CH 2 C1 (chloro- benzyl chloride). The majority of aromatic halogen derivatives, independently of the position of the halogen in the side chain or nucleus, react in dry ethereal solution (or in benzene in presence of a little dimethyl-aniline) with dry magnesium powder, yielding organo-magnesium compounds, e.g. C 6 H 5 -MgBr, phenyl-mag- 356 XIX. HALOGEN DERIVATIVES nesium bromide, C 6 H 5 CH 2 Mg Cl, benzyl-magnesium chloride, &c. These compounds Cmgnard's compounds are chemically extremely active, and, like the analogous aliphatic compounds (p. 120), can be employed for the syntheses of saturated and unsaturated hydrocarbons, primary, secondary, and tertiary alcohols, thiophenols, aldehydes, ketones, acids, &c., e.g.: 1. C 6 H 6 .Mg.Br + Br.C 2 H 6 = MgBr 2 + C 6 H 6 .C 2 H 6 . a C 6 H 5 .Mg.Br + = C 6 H 6 .O.MgBr. 2 - C 6 H 6 .0-MgBr + H 2 = C 6 H 6 .QH + Br-Mg-OH. , C 6 H 6 .Mg.Br + C0 2 = C 6 H 6 .CO 2 .MgBr. * C 6 H 6 .CO 2 MgBr + H.OH = C 6 H 6 -CO 2 H + OH-Mg.Br. and with water (C 6 H 6 ),C OH. The Grignard compounds may also be used for converting a bromo-derivative into the corresponding iodo-compound, e.g. : C 6 H 6 Br C 6 H 5 -M g .Br C 6 H 6 I + MgBrl. Mg I, The boiling-points of the isomeric halogen substitution pro- ducts differ but little from one another (cf. 0-, m- t ^?-chloro- benzene and benzyl chloride). The influence of the introduction of F, Cl, Br, or I in place of hydrogen on the boiling-point of a hydrocarbon is similar to that noted in the fatty series. Iodine raises the boiling- point to the greatest extent, and fluorine to the least. The halogen derivatives may be nitrated, sulphonated, &c., in much the same manner as benzene itself. Modes of Formation. 1. By the action of chlorine or bromine upon aromatic hydrocarbons there are formed, according to the conditions, either additive or substitution products, the latter class especially in presence of iodine or some other halogen carrier. The function of the halogen carrier, e.g. I, P, Fe, &c., is probably to form an additive compound with the halogen, e.g. IC1 3 , PC1 5 , FeCl 3 , then to give up part or the whole of the halogen in the nascent state to the hydro- carbon, and then to be immediately converted back into the above compounds again. (Cf. p. 56, also B. 18. 607.) Iodine only substitutes directly under the conditions detailed at p. 57. From benzene most of the chlorinated derivatives up to C 6 C1 6 can be obtained in succession; the last-named compound is formed with the aid of MoCl 5 , IC1 3 , &c., at a somewhat high temperature. A hexabromo-benzene and a hexa-iodo-com FORMATION OF HALOGEN DERIVATIVE^ 357 pound also exist. In the case of toluene and its hdniologues the halogen enters the benzene nucleus alone if the operation is performed in the cold, with the exclusion of direct sunlight or with the addition of iodine; while if the gas is led into the boiling hydrocarbon, or if the experiment is conducted in sun- light and without addition of iodine, it goes almost exclusively into the side chain (Beilstein; Schramm; see also B. 13, 1216). 2. From compounds containing oxygen (the phenols, aro- matic alcohols, aldehydes, ketones, and acids), by the action of phosphorus pentachloride or bromide: C 6 H 5 .OH + PC1 5 = C 6 H 6 C1 + POC1 3 + HC1; C 6 H 6 .CH:O + PC1 5 = C c H 6 .CHCl 2 -f POC1 3 . 3. From the primary amines. The amine is first converted into a diazonium salt (p. 385), and this is then warmed with solu- tions of cuprous chloride or bromide, when the corresponding chlorine or bromine compound is obtained. If the diazonium salt is warmed with potassium iodide solution, iodo-substitution products are obtained: C 6 H 5 .N(C1):N C 6 H 6 .N(C1):N + KI = C 6 H 6 I + N 2 + KC1. Gattermann 's modification consists in transforming the amine into the diazonium chloride, bromide, or iodide, and then de- composing this with finely-divided copper powder (Sandmeyw,, B. 17, 1633, 2650; Gattermann, B. 23, 1218): C 6 H 6 .NI:N = C 6 H 6 I + N 2 . The method is largely used for the preparation of halogen de- rivatives of benzene homologues, especially for iodo-derivatives, ^-Dibromo-benzene is obtained, together with bromo-ben- zene, by bromination of benzene in presence of a little iron. The trichloro-benzene which results by direct substitution has the (asymmetric) constitution 1:2:4. It may also be formed by the separation of 3HC1 from C 6 H 6 C1 6 . Hexachloro- and hexabromo-benzenes are produced by the prolonged chlorination or bromination of benzene, toluene^ naphthalene, &c., and also from carbon tetrachloride and bromide, as given at p. 343. They are solid and can be distilled. When toluene is chlorinated or brominated, as given on p. 356, the para- and ortho-compounds are formed in approxi- mately equal quantities. ra-Chloro-toluene is obtained from 358 XIX. HALOGEN DERIVATIVES chloro-^-toluidine, C 6 H 3 C1(NH 2 )CH 3 (from ^-toluidine and Ci), according to method 3. Oxidation by HN0 3 , Cr0 3 , or KMn0 4 converts them into the haloid-benzoic acids, but chromic acid mixture must only be used in the case of the p- and m-, and not in that of the 0-compounds, as it completely disintegrates the latter. Benzyl chloride, C 6 H 5 -CH 2 C1 (Cannizaro), is prepared by chlorinating boiling toluene, and benzyl bromide in an analo- .gous manner; the latter can be converted into benzyl iodide by potassium iodide solution. The behaviour of these com- pounds shows them to be the haloid esters of benzyl alcohol, 1 C 6 H 5 CH 2 OH, from which they may be obtained by the action of halogen hydride, or of halogen derivatives of phos- phorus, and into which they are transformed by prolonged boiling with water, or better, with a solution of potassium carbonate. When boiled with potassium acetate, the chloride yields benzyl acetate, with potassium sulph-hydrate the mer- captan, and with ammonia the amine. The compounds containing halogen in the side chain irritate the mucous membrane of the nose and eyes exceedingly, and on oxidation yield benzoic acid. Benzyl chloride is used on the large scale for the preparation of oil of bitter almonds and also of certain dyes. Benzal chloride, Benzylidene chloride, C 6 H 5 CHC1 2 , and benzo-trichloride, C 6 H 5 CC1 3 , are produced by the further chlorination of boiling toluene and also by the action of PC1 5 upon the corresponding oxygen compounds, benzaldehyde, C 6 H 6 CHO, benzoic acid, C 6 H 5 C0 2 H, and benzoyl chloride, C 6 H 5 COC1. They are liquids resembling benzyl chloride, and are reconverted into the original oxygen compounds by superheating with water, and into benzoic acid by oxidizing agents. Chlorobromo-benzenes, C 6 H 4 ClBr, chlor-iodo-benzenes, and other mixed derivatives also exist in large number. Substitution compounds of unsaturated hydrocarbons are likewise known, e.g. /3-bromo-styrene, C 6 H 5 CBr : CH 2 , a- bromo-styrene, C 6 H 5 CH : CHBr, &c. Iodine Derivatives containing a Polyvalent Iodine Atom. The iodine atom attached to the nucleus may in many cases unite with other atoms, and thus exercise a higher valency. The compounds thus obtained have but few analogues in the fatty series. Phenyl-iodide dichloride, C 6 H 5 I:C1 2 (Willgerodt), is formed NITRO-COMPOUNDS 359 as a yellow crystalline compound when dry chlorine is led into a chloroform solution of phenyl iodide. The chlorine is loosely combined, and may be removed on warming, or by the action of potassium iodide. Alkalis transform the dichloride into iodoso- benzene, CgH 5 -I:0, a yellow amorphous sub- stance which dissolves in acids, yielding salts, e.g. acetate, C 6 H 5 .I(C 2 H 3 2 ) 2 , nitrate, C 6 H 6 .I(0-NO ? ) 2> &c. It decom- poses when heated, oxidizes potassium iodide solution, and when kept or when distilled in steam is converted into phenyl iodide and iodoxy-benzene, C 6 H 5 -I0 2 . This latter is crystal- line, explodes when heated, is not basic, and resembles per- oxides. It may also be prepared by oxidizing the iodoso- compound with Card's reagent. lodonium compounds (Hartmann and V. Meyer, B. 27, 1592), e.g. diphenyl-iodonium iodide, (0 6 H 5 ) 2 II, and the correspond- ing hydroxide, (C 6 H 5 ) 2 I OH, can be obtained when a mixture of iodoso- and iodoxy-benzene is shaken with moist silver oxide: H = (C 6 H 6 ) 2 I.OH + AgIO 3 . The hydroxide which is only known in solution has strongly alkaline properties. The salts, which crystallize well, closely resemble the thallium salts. It is highly probable that the three valencies of the polyvalent iodine atom in these iodo- nium salts lie in the same plane, as, according to Peters and Kipping (J. C. S. 1902, 1350), stereo-isomerides of the form RR'I X do not appear to exist, and no resolution into optically active components can be effected. XX. NITRO-SUBSTITUTION PKODUCTS OF THE AROMATIC HYDROCARBONS When benzene and its derivatives are treated with concen- ;rated nitric acid, most of them are easily dissolved, with evo- ution of heat, and transformed into mtro-compounds which re precipitated on the addition of water. According to the onditions of the experiment and the nature of the compound ;o be nitrated, one or more nitro-groups enter the molecule see, e.g., phenol). The nitro-groups substitute in the nucleus, nd only very seldom in the side chain (cf. p. 363). Very often fuming nitric acid or a mixture of fuming nitric nd concentrated sulphuric (or fuming sulphuric) acid is used. 360 XX. AROMATIC NITRO-COMPOUNDS The advantage of the addition of sulphuric acid is to absorb the water formed during nitration, and thus to keep the nitric acid from becoming too dilute. The stronger the acid and the higher the temperature, the larger the number of nitro- groups introduced. The homologues of benzene are, as a rule, nitrated more readily than benzene itself. SUMMARY CH^NO> Nitro-benzene . . Positions of Substituents. M.-p. +3 B.-p. 908 Sp. gr. 1.204 C fl H 4 (N0 2 ) 2 . .. o-Dinitro-benzene.... 1:2 117 319 C 6 H 8 (N0 2 ) 8 CHs-CeH^NO.,... m-Dinitro-benzene ... 2>-Dinitro-benzene ... . s-Trinitro-benzene . . . os-Trinitro-benzene . o-Nitro- toluene wi-Nitro-toluene . 1:3 1:4 1:3:5 1:2:4 *1:2 1:3 90 172 122 57-5 -10-5 + 16 302 299 t 218 ?30 1-168 1-168 ^?-Nitro-toluene 1:4 51 934 f 1-123 CH8.C 6 H V (N0 2 ) 2 (CH 8 )2 C 6 H 8 N0 2 2:4-Dinitro-toluene . . . 2:6-Dinitro-toluene . . . 4-Nitro-xylene . . . . 1:2:4 . 1:2:6 . 1:3:4 70 66 +2 t 946 \ (54) 1 -135 (CH^CJL.NO,.. Nitro-mesitvlene. . . , . 1:3:5:2 44 255 Nitro-compounds are also produced by the action of nitrous acid upon diazonium compounds in the presence of cuprous oxide (Sandmeyer, B. 20, 1494): C 6 H 6 NC1:N + HN0 2 = C 6 H fi .N0 2 + HC1 + N 2 , and also by the oxidation of primary aromatic amines : C 6 H 5 .NH 2 C C H 6 .N0 2 (Bamberger, B. 1893, 26, 496). These reactions, however, are mainly of theoretical interest. They cannot, however, be prepared according to mode of formation 1 for nitro-methane (p. 94), i.e. by the action of AgN0 2 on C 6 H 5 C1, &c. The nitro-compounds are, for the most part, pale-yellow liquids which distil unchanged and volatilize with water vapour; some form colourless or pale-yellow crystals; some- times they are also of an intense yellow or red colour. Many * The positions of CH 3 group, or groups, are always given first. t Most of the polynitro-compounds are not volatile, but decompose when heated. #ALOir> NITRO-COMPOUNDS 361 of them explode when heated. They are heavier than water, and insoluble in it; but most of them are readily soluble in alcohol, ether, and glacial acetic acid. The nitro-group in most aromatic nitro-compounds is bound very firmly, as in the case of the nitre-methanes, and is not exchangeable for other groups. Like the latter compounds also, they are readily reduced in acid solution to the corre- sponding amines; in alkaline solution they are converted into azoxy-, azo-, and hydrazo- compounds (see these), and in neutral solution into hydroxylamine derivatives. When reduced electrolytically, nitro -benzene can yield either phenyl-hydroxylamine, C 6 H 5 NH-OH, which is imme- diately transformed into p-amino- phenol, OHC 6 H 4 NH 2 (Gattermann, B. 1893, 26, 1814; 1894, 27, 1927), or it can yield aniline. Other nitro-compounds can be reduced in a similar manner. When hydrogen is passed into an alcoholic solution of nitro-benzene containing colloidal palladium, aniline is formed. Nitro-benzene, C 6 H 5 (N0 2 ) (Mitscherlich, 1834), is formed when a mixture of sulphuric and the calculated quantity of nitric acid is added to benzene. It is a yellowish liquid with an intense odour of oil of bitter almonds, which solidifies in the cold, and melts at +5. Dinitro-benzenes, C 6 H 4 (N0 2 ) 2 are produced when benzene is boiled with fuming nitric acid; in this, as in all analogous cases, the two nitro groups take up the meta-position to one another, very little of the o- and ^-compounds being formed, and after crystallizing from alcohol, pure m-dinitro-benzene is obtained in long colourless needles. The 0-compound crystallizes in plates and the ^-compound in needles, both being colourless; they are prepared indirectly by eliminating NH 2 from the corresponding di-nitranilines. When reduced, they yield first the three nitranilines, and then the phenylene-diamines (pp. 374 and 380). o-Dinitro-benzene exchanges a nitro-group for hydroxyl when boiled with caustic soda, and for an amino-group when acted on by ammonia, yielding o-nitro-phenol, C 6 H 4 (N0 2 )(OH), and 0-nitraniline, C 6 H 4 (N0 2 )(NH 2 ), respectively. These reactions appear to be characteristic of all compounds containing two nitro-groups in ortho-positions. The ?w-compound is oxidiz- able by K 3 FeC 6 N 6 to a- and /3-dinitro-phenol. s-Trinitro-benzene crystallizes in colourless plates, melts at 122, and forms additive compounds with aromatic hydro- 362 XX. AROMATIC NITRO-COMPOUNDS carbons, phenols, and especially with aromatic bases, e.g. ani- line, naphthylamine. Most of these are well-defined crystal- line compounds of red, reddish-brown, or black colour, and are readily resolved into their components by warm mineral acids (A. 1882, 215, 344; J. C. S. 1901, 522; 1903, 1334; 1906, 583; 1910, 773). Nitro-toluen.es, CH 3 C 6 H 4 N0 2 . When toluene is nitrated, the p- and 0-compounds, with very little wi-compound, are formed. The first is solid, crystallizing in large prisms, and the second liquid, the latter being used as a perfume under the name of " oil of mirbane"; both are employed in the colour industry. m-Nitro- toluene can be prepared indirectly from m-nitro-^-toluidine, C 6 H 3 (CH 3 )(NO 2 )(NH 2 ), by the elimination of the ammo-group (p. 387). Further nitration gives rise to: Dinitro- toluenes, CH 3 C 6 H 3 (N0 2 ) 2 , of the constitution OH 3 :N0 2 :N0 2 = 1:2:4 and 1:2:6, the two nitro-groups being again in the m-position to one another in both cases. (Cf. p. 361.) Most of these nitro-compounds are of great technical im- portance, on account of the readiness with which they are reduced to amines. Trinitro-tertiary-butyl-toluene, C 6 H(CH 3 )[C(CH 3 ) 3 ](N0 2 ) 3 , is used as "artificial musk". Chloro- and Bromo-nitro-benzenes, When chloro- or bromo- benzene is nitrated, ^-chloro- (or bromo-) nitro-benzene is formed, together with smaller quantities of the o-compounds. The ra-compounds "must be prepared indirectly by replacing an amino-group in m-nitraniline by halogen. The ^-deriva- tives have a higher melting-point than their isomers, and the m-compounds for the most part a higher one than the 0-deri- vatives, this law frequently repeating itself in other cases also. The p-derivatives are usually also less soluble in alcohol. The o- and ^-compounds, but not the w-, exchange halogen for hydroxyl when boiled with potash, and for the amino-group when heated with ammonia. In s-trinitro-chloro-benzene, C 6 H 2 (N0 2 ) 3 C1, and in 1-chloro- 2 : 4-dinitro-benzene the chlorine atoms have been rendered so readily exchangeable, that the compounds behave as alkyl chlorides, or even as acid chlorides; hence the name "picryl chloride", the chloride of picric acid (p. 414), for the former compound. 0-, m- y and ^-Nitro-cinnamenes, C0H 4 (N0 2 )(C 2 H 3 ), can be prepared by indirect methods. a-Nitro-styrene, C 6 H 6 -CH; PHENYL-NITRO-METHANE 363 CH'N0 2 , which is formed by the action of nitrous acid on cinnamene, contains the nitro-group in the side chain, since it can be prepared from benzoic aldehyde and nitro-methane by means of zinc chloride, thus: C 6 H 6 CHO + CH 3 NO 2 = C 6 H 6 . CH : CH . NO 2 + H 2 O. o-Nitro-phenyl- acetylene, N0 2 C 6 H 4 C CH, is formed when o-nitro-phenyl-propiolic acid is boiled with water. It crystallizes in colourless needles. Phenyl-nitro-methane, C 6 H 5 CH 2 N0 2 , isomeric with the nitro-toluenes, is the most typical of the aromatic nitro-deriva- tives with a nitro-group in the side chain. It is formed by the action of nitric acid (D 1-12) on toluene under pressure, and also by the action of benzyl halides on silver nitrite (cf. Nitro- methane). It is a true nitro-derivative, and not an alkyl nitrite (benzyl nitrite, C 6 H B .CH 2 .O.N:0), as it is not readily hydrolysed, and when reduced yields benzylamine, C 6 H 5 CH 2 -NH 2 . It exists in two distinct modifications, which are readily transformed into each other. As generally prepared, it is a colourless liquid with a characteristic odour, boils at 225-227, and dissolves to a certain extent in water, yielding a solution which does not give a coloration with ferric chloride. The second modification, which is a crystalline solid melting at 84, is formed when the sodium derivative obtained from the oily compound is decomposed in the cold by hydrochloric acid. The solid modification is relatively unstable, and when kept, gradually passes over into the oily form. The solid is probably a hydroxy-compound, since (a) its aqueous solution gives a red-brown coloration with ferric chloride, (b) it reacts with phenyl-carbimide, (c) it reacts with PC1 5 , and (d) with benzoyl chloride it gives dibenzhydroxamic acid, C 6 H 6 .CO.NH.O.COC 6 H 5 (from The solid would thus be represented by the formula: C 6 H 6 .CH:NO-OH or perhaps C 6 H 5 .CH-N.OH, O -an &09ulr0-fonnula, the sodium salt by C 6 H 5 CH:NO'ONa, and the oil by C 6 H 5 -CH 2 -N0 2 . The tendency to form iso- nitro-compounds is also shown by certain aliphatic nitre-com- pounds. 364 XX. AROMATIC NITRO-COMPOUND8 The oily compound, although it gives rise to a sodium salt, is, strictly speaking, not an acid ; it is what is termed a pseudo- acid, and before it yields a sodium salt it undergoes intra- molecular rearrangement, yielding the true acid the isomtro- compound. When the sodium salt is treated with a mineral acid, the fsonitro-compound, or true acid, is first formed; but as this is unstable, it gradually changes over into the true nitro- or pseudo-acid form. Numerous examples of pseudo- acids, i.e. compounds which on formation of metallic salts undergo intramolecular rearrangement so that the original substance has a structure different from that of the salt, have been investigated by Hantzsch (B. 1899, 32, 575; 1902, 35, 210, 226, 1001; 1906, 39, 139, 1073, &c.), who describes the following as some of the most characteristic criteria of pseudo-acids: 1. The compound is a pseudo-acid if it gradually neutralizes an alkali. The pseudo-acid, as such, does not neutralize the base, but is first transformed into the isomeric true acid, which then neutralizes the alkali. If the transformation is slow, then the process of neutralization is also slow. Similarly, if when a solution of a salt of the acid is decomposed by an equivalent quantity of a mineral acid, the electrical conductivity gradually falls to that required for the metallic salt of the mineral acid, it indicates that the acid is a pseudo-acid, e.g. barium esonitro-methane +HC1 give isonitro-methane +BaCl 2 , and then nitro-methane -f-BaCl 2 . Isonitro-methane is a fairly strong acid, and hence is dissociated to an appreciable extent; as it becomes transformed into nitro-methane (the pseudo- acid) the conductivity will diminish, as nitro-methane is an extremely feeble acid scarcely ionized. 2. If the original compound is extremely feebly acidic, and yet yields a sodium derivative which dissolves in water yield- ing a practically neutral solution, then the compound must be a pseudo-acid. It is a well-known fact that only sodium salts derived from comparatively strong acids, e.g. NaCl, Na 2 S0 4 , Nal, &c., dissolve in water to neutral solutions, i.e. are not hydrolysed by water. The sodium salts derived from feeble acids are always appreciably hydrolysed, e.g. Na 2 C0 8 , CH 3 COONa, &c. Hence if the sodium salt is not hydrolysed to an appreciable extent, the salt must be derived from a strong acid (the true acid), and the non- or feebly acidic compound must be the pseudo-acid. 3. If the compound in question will not yield a salt with ammonia in an anhydrous solvent, e.g. dry benzene, but will NITROSO-DERIVATIVES 365 do so in the presence of water, e.g. in moist ether, then the substance is a pseudo-acid. The formation of a salt in dry ether does not necessarily indicate that the substance is a true acid. 4. If the compound dissolves in water or in other dissociating (ionizing) media to a colourless solution, but yields a coloured solid salt or coloured ions when dissolved in alkalis, it is a pseudo-acid. 5. An abnormally high temperature coefficient for the elec- trical conductivity and an increase in the coefficient with rise of temperature are further indications of pseudo-acids. Nitro- methane, bromo-nitro-methane, dibromo-nitro-meth- ane, nitro-ethane, phenyl-nitro-methane, phenyl-bromo-nitro- methane, in addition to numerous other organic compounds, e.g. cyanuric acid, react as pseudo-acids. NITROSO-DERIVATIVES OF THE HYDROCARBONS Nitroso-benzene, C 6 H 5 .N:0, an aromatic compound which contains the nitroso-group, N:0, in place of a benzene hy- drogen atom, is produced by the action of nitrosyl chloride, NO'Cl, upon mercury diphenyl dissolved in benzene; it is also obtained by the oxidation of diazo-benzene with alkaline permanganate, and most readily by the oxidation of phenyl- hydroxylamine with chromic acid or ferric chloride. It forms colourless plates, melts at 68, yields green solutions, and pos- sesses a powerful odour similar to that of cyanic acid. When reduced it yields aniline, and when oxidized nitro-benzene. It readily condenses with different compounds, e.g. with ani- line in the presence of acetic acid to azo-benzene: C C H 5 .N:0 + H 2 N.C 6 H 6 = H 2 O + C 6 H 5 .N:N.C 6 H fi) and with phenyl-hydroxylamine to azoxy-benzene. Nitroso-derivatives of tertiary amines are obtained directly by the action of nitrous acid upon the latter. (See Nitroso- dimethyl-aniline, NQ.C 6 H 4 .N(CH 3 ) 2 , p. 378.) 366 XXI. ARYLAMINKS XXL AMINO-DERIVATIVES OR ARYLAMINES* (See Table, p. 367.) Aniline, the simplest of the aromatic bases, may be regarded (1) as benzene in which a hydrogen atom is replaced by the amino-group ("amino-benzene"), or (2) as ammonia in which a hydrogen atom is replaced by phenyl, C 6 H 5 , ("phenyl- amine"). According to the former view, ammo-compounds can be derived from all the benzene hydrocarbons, and not only monamines (containing NH 2 ), but also diamines (2NH 2 ), triamines, &c.; according to the latter, the phenyl group may enter anew with the formation of secondary or tertiary amines. Secondary and tertiary amines, and even quaternary ammonium compounds, may also result from the entrance of alky 1- radicals into the above monamines, diamines, &c. Amines are also known in which the NH 2 group is attached to a carbon atom of a side chain, e.g. C 6 H 5 CH 2 NH 2 . These compounds differ in many respects from aniline and its homo- logues. An extraordinarily large number of aromatic bases are thus theoretically possible, and also actually known. In certain respects they closely resemble the aliphatic amines, e.g. they form salts with acids, e.g. (XH 5 NH 2 , HC1, and complex salts, e.g. platinichlorides and auricnlorides, 2C 6 H 5 NH 2 , H 2 PtCl 6 and C 6 H 6 NH 2 , HAu01 4 ; they possess a basic odour, give rise to white clouds with volatile acids, and distil for the most part unchanged, &c. As a rule, however, they are weaker bases than the aliphatic amines, since the phenyl group, C 6 H 5 , pos- sesses a negative character, and not like the alphyl radicals a positive; thus the salts of diphenylamine are decomposed even by water, and triphenylamine no longer possesses basic properties, while dimethyl-aniline has a strongly-marked basic character. * To distinguish between monovalent alcoholic or hydrocarbon radicals of the fatty and aromatic series the following system has been suggested : The term alkyl group comprises all such monovalent radicals whether of the aliphatic series, e.g. CH 8 , C 2 H 5 , or of the aromatic, e.g. CH fc CH s .C 6 Ht, C 6 H 5 'CHo, &c. The purely aliphatic alkyl radicals are termed alphyl groups, and the aromatic, aryl ( Vorlander, J. pr. [2], 69, 247). Thus anil/ ue is often spoken of as a type of the arylamines. PRIMARY MONAMINES 367 The diamines have a more strongly basic character than the monamines, and are more readily soluble in water. ANILINE AND ITS HOMOLOGUES Formula. C fl H,.NH 9 .. Name. 1 Positions of iubstituents NH 2 in 1. M.-p. B.-p. 8 183 M.-p. of Acetyl Derivative. 115 CJELMe-NH,.. o-Toluidine 1-2 liq 199 110 1:3 liq. 199 65'5 #-Toluidine ... 1:4 42 '8 198 153 C 6 H 3 Me 2 -NH 2 .. ac?/.-0-xylidene .... wnsywi.-o-xylidene ac^'.-m-xylidene. . . -xylidene 1:2:3 1:3:4 1:2:6 1:2:5 liq. 223 49 226 liq. 215 15'5 215 134 99 176 139 C 6 H 2 Me 3 NH 2 . Mesidine 1-2-4-6 liq 233 216 C 6 H 6 -NHMe... C 6 H 6 .NMe 2 Pseudo-cumidine . Methyl-aniline.... Dimethyl-aniline . 1:2:4:5 68 234 ... 192 ... 192 ... 204 164 101-102 54'5 (lld-NEt, Diethyl-aniline . . 213 183 60 A. Primary Monamines Isomers. The isomerism of the aromatic is in part analogous to that of the fatty amines (p. 107), e.g. dimethyl-aniline is isomeric with the methyl-toluidines and the xylidines. Cases of isomerism are also caused by the amino-group being present in the benzene nucleus in the one case, and in the side chain in the other. Finally, position isomerides are frequently met with, e.g. 0-, m-, and ^-toluidines, CH 3 C 6 H 4 NH 2 . Constitution. As already seen at pp. 108 et seq., amines are very easy to characterize as primary, secondary, &c. In addition, their modes of formation, and also their behaviour, show whether the amino-group of a primary amine is present in the benzene nucleus or in the side chain. Modes of Formation. 1. The most important mode of pre- paration of the primary arylamines, whether mono- or di-, &c., is the reduction of the corresponding nitro-compounds : C 6 H 6 .N0 2 Nitro-benzene C 6 H 4 (N0 2 ) 2 H Diuitro-benzene Aniline. 4H 2 + C 6 H 4 (NH 2 ) 2 Phenylene-diamine. 368 XXI. ARYLAMINES The usual method of introducing an ammo-group into a benzene hydrocarbon is to first nitrate and then reduce. An interesting direct method for the introduction of the NH group is by the action of ferric or aluminic chloride on a mixture of the hydrocarbon and hydroxylamine hydrochloride (B. 1901, 34, 1778): NH.OH = The reduction of nitro- to amino-compounds takes place most readily in acid solution, e.g. by the gradual addition of the former to a warm mixture of tin or stannous chloride and hydrochloric acid. On a manufacturing scale, iron and a limited amount of hydrochloric acid are used (Be~champ\ also frequently zinc dust and hydrochloric or acetic acid. Am- monium sulphide (Zinin), ferrous sulphate, and baryta water, &c., also effect the reduction. (See Aniline and chapter on Eeduction.) Aniline and its homologues may also be obtained by the electrolytic reduction of nitro-compounds. Ammonium sulphide acts more mildly than tin and hydro- chloric acid, and is therefore of special value for the partial reduction of dinitro-compounds (see Nitraniline). An alcoholic solution of stannous chloride containing hydrochloric acid may also be used for this purpose (B. 19, 2161). Amines are also formed when nitroso-compounds and aryl- hydroxylamines are reduced. 2. By heating phenols with the compound of zinc chloride and ammonia, or of calcium chloride and ammonia, to 300 (Merz), secondary amines being formed at the same time: C 6 H 6 .iOH"+H;NH 2 = This reaction proceeds more easily in the presence of nega- tive groups, e.g. with the mtro-phenols (B. 19, 1749). 3. By distilling amino-acids with lime, sometimes by merely heating them alone : NH 2 .C 6 H 4 .C0 2 H = C 6 H 6 .NH 2 -hC0 2 . 4. When the hydrochlorides of secondary and tertiary amines of the type of mono- and di-methyl-aniline are heated in sealed tubes, the methyl groups wander from the nitrogen atom to a carbon atom of the benzene nucleus, e.g. methyl- aniline hydrochloride at 335 yields toluidine hydrochloride: C fl H 6 .NHCH 3 ,HCl ^ CH 3 .C C H 4 .NH 2 ,HCL PROPERTIES OF PRIMARY ARYLAMINES 369 The methyl groups invariably take up the o- or p-, and not the m- position, with respect to the amino-group. Q Similarly, the final product obtained by heating phenyl- trimethylammonium iodide, C 6 H 5 'NMe 3 I, is mesidine hy- driodide, C fl H 2 Me 8 NH 2 [NH 2 : Me 3 = 1 : 2 : 4 : 6*J. ftiphenyl- amine hydrochloride does not behave in a similar manner. This reaction, often known as the Hofmann reaction, is of considerable service in obtaining the higher homologues of aniline from aniline, toluidine, &c. Aniline is readily con- verted into dimethyl-aniline, and when the hydrochloride of this is heated to about 300 the methyl groups wander from the side chain into the nucleus: C 6 H 6 .NMe 2 C G H 3 Me 2 .NH2. 5. Primary amines can be obtained from acid amides by Hofmann' s reaction (cf. p. 183), viz. treatment with bromine and alkali, or from acid azides, K-CO'N 3 . When boiled with alcohol the azide yields nitrogen and, by molecular rearrange- ment, a urethane, RNH'COOEt, and this on hydrolysis gives a primary amine, RNH 2 . 6. The aromatic amines cannot, as a rule, be obtained by heating chloro-benzene, &c., with ammonia unless there is a nitro-group in the ortho- (or para-) position with respect to the halogen. Benzylamine, however, and all analogously constituted bases, which contain the NH 2 group in the side chain, can be obtained by the methods employed for the pre- paration of aliphatic amines. Thus benzylamine is formed by the action of ammonia, or better, of acetamide upon benzyl chloride (the latter method gives acetyl-benzylamine, which can be readily hydrolysed). Properties. The primary monamines are either liquid or solid crystalline bases. They are colourless when pure, but readily become brown when exposed to the air, largely owing to the presence of small amounts of impurities, and possess a weakly basic though not disagreeable odour. Ani- line is somewhat soluble in water (1:31), its homologues less so. Behaviour. 1. With acids most of them form crystalline salts, the majority of which are readily soluble in water. They do not, however, unite with very weak acids, such as * The numbers 1:2:4:6 indicate the relative positions of the amino- and three methyl -radicals in the benzene ring. (B480) ?A 370 XXI. ARYLAMINES carbonic, and they are therefore separated from their salts in the free state by sodium carbonate, and in some cases even by sodium acetate (when no acetates exist). They yield com- plex salts, such as platinichlorides, (C 6 H 5 NH 2 ) 2 , H 2 PtCl 6 , ami- chlorides, C 6 H 5 NH 2 , HAuCl 4 , ami similar compounds with stan- nous, stannic, and zinc chlorides. The platinum double salts are often sparingly soluble, and therefore suited for the isolation of the bases. All salts of the bases are readily decomposed by strong alkalis, and the free bases are regenerated. Even in aqueous solution the salts are largely split up into free acid and free base; the result is that the strength of a solution of aniline hydrochloride may be determined by titrating the hydrochloric acid present by standard alkali hydroxide, using phenol- phthalein as indicator. This is not due to the fact that the salt is completely hydrolysed in aqueous solution; in reality there is a state of equilibrium represented by the equation: C 6 H 6 .NH 3 C1 ^ C 6 H 6 NH 2 + HC1, and as the HC1 is neutralized by the addition of alkali, more of the aniline salt is decomposed in order to restore the equi- librium. This continues until the whole of the salt is decom- posed, and the HC1 neutralized by the alkali. The amines also form additive compounds with numerous metallic salts, e.g. 2C 6 H 7 N + ZnCl 2 , 2C 6 H 7 N + HgCl 2 , &c. 2. When aniline is heated with potassium or sodium, the hy- drogen is replaced by metal with formation of the compounds CgH 5 NHK and C 6 H 5 NK 2 . These yield di- and tri-phenylamine with bromobenzene, and decompose immediately with water. 3. The primary arylamines react with methyl iodide, benzyl chloride, &c., yielding secondary, tertiary, and even quaternary compounds : = C 6 H 5 .NH(CH 3 ),HI; C 6 H 5 .NH(CH 3 ) + CH 3 I = QgHs-NC C 6 H 6 .N(CH 3 ) 2 + CH 3 I = C 6 H 5 .N(CH 3 ) 3 I. The secondary and tertiary bases can be liberated from their hydriodides by soda, but moist oxide of silver must be used in the case of the ammonium bases (see p. 109). 4. Just as the ammonium salts of acids can eliminate water, yielding amides, so the aniline salts can yield anilides, e.g. aniline acetate gives acetanilide: CH 3 .CO-ONH 3 C 6 H 6 = CH 3 .CO-NHC 6 H 6 -fH a O. ANILIDES. ISONITRILES 371 These anilides may be looked upon either as acetylated amines or as phenylated amides, the formula CH 3 CO- NHC 6 H 5 corresponding with the latter view. They are in every respect analogous in their chemical behaviour to the ordinary amides, especially to the alkylated amides (p. 182), being hydrolysed to the acid and aniline by alkalis, and being formed by analogous methods, e.g. by heating the acid, or better, its anhydride or chloride, with the amine in question, thus : CH 3 C 6 H 4 NH 2 + CH 3 COC1 = CH 3 C 6 H 4 . NH CO CH 3 + HC1. Toluidiue Acet-toluidide 5. Aliphatic aldehydes react with the primary bases, with elimination of water, thus: CH 3 .CHO-f 2C 6 H 6 .NH 2 = CH 3 .CH(NH.C 6 H 5 ) 2 -f H 2 O. Ethylidene-diphenyl-diamine Aromatic aldehydes, however, react as follows : C 6 H 5 CHO + NH 2 C 6 H 6 = C 6 H 6 . CH : N C 6 H 6 + H 2 0. In this case an additive compound appears to be first formed, C 6 H 5 .CH(OH).NH-C 6 H 5 , and this loses water, yielding ben- zylidene aniline, C 6 H 5 CH : N C 6 H 5 . Condensation products of this latter kind (Schiff's bases) can also be obtained with the fatty aldehydes, but they poly- merize readily (v. Miller, Plochl, B. 25, 2020). 6. When warmed with chloroform and alcoholic potash, the primary bases, like those of the fatty series, yield isonitriles of stupefying odour. When they are warmed with carbon disulphide, thio-ureas are formed, and from the latter isothio- cyanates (mustard oils) by treatment with phosphoric acid (cf. pp. 276 and 296). 7. Bromine and chlorine, especially in the form of sodium hypochlorite or hypobromite, react with amines, forming sub- stituted derivatives of the type C 6 H 5 -NHBr, in which the halogen is attached to nitrogen. These compounds are ex- tremely unstable, can only be kept at low temperatures, and the halogen atom readily passes from the side chain into the benzene nucleus: C fl H 6 .NHBr usually into the para-position (Chattaway and Orton, J. C. S. 1899, 1046; 1900, 134, 152, 789, 797). 372 XXI. AR FAMINES 8. Nitrous acid converts the primary aromatic amines in acid solution into diazonium salts (p. 385), and in the absence of acids into diazo-amino-compounds (p. 392). 9. The oxidation products of the primary bases are very various, azo-benzene, nitro-benzene, ^-amino-phenol, phenols, quinones, azo-compounds, aniline black, &c., resulting accord- ing to the conditions; a mixture of aniline and toluidine yields magenta (fuchsine) (see Triphenylmethane dyes). 10. The bases which contain the amino-group in the side chain possess, in contradistinction to the purely aromatic amines, the character of the amines of the fatty series, and cannot, therefore, be diazotized. Aniline, ammo-benzene, Phenylamine, C 6 H 5 NH 2 , was first obtained in 1826 by Unverdorben from the dry distillation of indigo, and termed by him "crystalline"; then Eunge found it in coal-tar in 1834, and called it "cyanol". In 1841 Fritsche prepared it by distilling indigo with potash, and gave it the name of aniline; while in 1842 Zinin obtained it by the reduction of nitro-benzene, and called it " benzidam ". It was accurately investigated by A. W. Hofmann in 1843, and he was able to show that all the above products are identical. It is present in small quantities in coal-tar and also in bone- oil. Preparation. Since 1864 aniline has been prepared on a manufacturing scale by reducing nitro-benzene with iron filings and a regulated quantity of hydrochloric acid, and distilling with steam after the addition of lime. The amount of hydrochloric acid actually employed is only about j^th of that required by the equation: = C 6 H 6 -NH 2 + 2H 2 + 3FeCl 2 . This is probably due to the fact that water and metallic iron, in the presence of ferrous chloride, can act as reducing agents. It is a colourless, oily, strongly refracting liquid of peculiar odour, which quickly turns yellow or brown in the air, and is finally converted into a resin. It dissolves in 31 parts of water, has no action upon litmus, and is a weaker base than ammonia, although it can displace the latter at higher tem- peratures. It is poisonous, burns with a smoky flame, and is a good solvent for many compounds which are otherwise not readily dissolved, e.g. indigo and sulphur. Aqueous solutions of the salts have a distinct acid reaction. The behaviour of aniline has been investigated with the ANILINE 373 utmost care. Oxidation in alkaline solution leads to azo- benzene, while arsenic acid produces chiefly violaniline, a violet colouring-matter. A solution of free aniline is tem- porarily coloured violet by one of bleaching- powder, this reaction being an extremely delicate one. A solution in con- centrated H 2 S0 4 is first coloured red and then blue by a small grain of potassium dichromate. A solution of K 2 O 2 7 pro- duces in an acid solution of aniline sulphate a dark-green and then a black precipitate of aniline black (Willstdtter, B. 1907, 40, 2665; 1910, 43, 2976; Green, J. C. S. 1910, 2388; B. 1911, 44, 2570), and ultimately quinone, C 6 H 4 2 . A mixture of aniline and toluidine may be oxidized to magenta, mauveine, &c., and a mixture of aniline and j9-diamines to safranines (see these). When reduced, aniline yields amino-hexamethylene, boiling at 134. Salts. Aniline hydrochloride, C 6 H 5 *NH 2 , HC1, forms large colourless plates which become greenish-grey in the air and distil unchanged, and aniline sulphate, (C 6 H 7 N) 2 , H 2 S0 4 , beau- tiful white plates, sparingly soluble in water. The platini- chloride, (C 6 H 7 N) 2 , H 2 PtCl 6 , crystallizes in yellow plates, which are sparingly soluble. Substitution Products Halogen 'Derivatives. Aniline is much more readily substituted by halogens than benzene, chlorine or bromine causing substitution of as many as three atoms of hydrogen, yielding s?/w-trichlor- or -tribrom-aniline, while iodine produces mono-iodoaniline. In the chlorination of ani- line it is necessary to use a solvent free from water (e.g. chloroform or glacial acetic acid), otherwise oxidation and not substitution occurs. In bromination the simplest method is to aspirate air saturated with bromine vapour through an acid solu- tion of aniline. In all these reactions the halogen probably first substitutes H of the NH 2 group (see p. 371). In the preparation of monochlor-aniline, the aniline must be "pro- tected" by using it in the form of its acetyl derivative, acetanilide. When this is suspended in water, it is mostly transformed by chlorine into p - chlor - acetanilide, which readily yields p-chlor-aniline on hydrolysis ; the latter forms colourless crystals, m.-pt. 71, b.-pt. 231. The o- and m-com- pounds, which are both liquid, are prepared indirectly, e.g. by the reduction of o- or m-chloro-nitro-benzene. The basic character is weakened in the mono-chlor-anilines by the entrance of the halogen, this being the case particularly in the 0-compounds. It is still more striking in s-tri chlor- 374 XXI. ARYLAMINJCS aniline, C 6 H 2 C1 3 (NH 2 ) (crystals, volatile without decomposi- tion), which no longer combines with acids in presence of water, o- and ^-Chlor-anilines are only capable of taking up two more atoms of chlorine with the formation of trichlor- aniline: [NH 2 : Cl : Cl : Cl = 1.2.4.6]; ra-chlor-aniline, on the other hand, can be further chlorinated to tetra- and penta- chlor-aniline. The bromo-derivatives of aniline closely resemble the chlor- anilines, and may be prepared by similar methods. The best- known compound is s-tribrom-aniline, which is formed by the action of bromine water on a solution of aniline hydrochloride. It crystallizes from alcohol in needles, and melts at 119. As an example of the methods sometimes employed for the preparation of halogen derivatives may be cited the prepara- tion of 2 : 6-dibrom-aniline from sulphanilic acid, 1-amino-ben- zene-4-sulphonic acid. When carefully brominated, this yields the 2 : 6-dibromo-derivative ; and when this is superheated with steam at 170 the sulphonic acid group is removed, and 2:6- dibrom-aniline, melting at 84, is formed. Nitranilines. Aniline is likewise attacked far more vio- lently than benzene by concentrated nitric acid, and therefore when it is wished to prepare the mono-nitro-compounds, the aniline must again be " protected ", either by using its acetyl compound, or by nitrating in presence of excess of concen- trated sulphuric acid. In the latter case all three nitranilines result, the m-compound preponderating. When acetanilide is nitrated, p-nitr acetanilide, N0 2 .C 6 H 4 -NHCO.CH 3 , and a little of the o-compound, are formed, and both are readily hydrolysed by potash or hydrochloric acid. The nitranilines are further obtained by the partial reduc- tion of the corresponding dinitro-benzenes, e.g. by means of ammonium sulphide; this is the method usually employed for the preparation of m-nitraniline. (For mechanism of the re- action, see Cohen and M'Candlish, J. C. S. 1905, 1257.) The o- and ^-compounds are also formed when o- and p- C 6 H 4 C1.N0 2 , C 6 H 4 Br.N0 2 , OH.C 6 H 4 .N0 2 , or OEt.C 6 H 4 .NO ? are heated with ammonia at 180, and conversely the o- and p-nitranilines are converted into nitro-phenols when boiled with alkalis, the former more easily than the latter, thus: - C fl H 4 (N0 2 )(NH 2 ) -f H-OH = C 6 H 4 (N0 2 )OH + NH 3 . These are all further examples of the remarkable influence of nitro- groups on other substituents, e.g. Cl, Br, OH, TOLUIDINE! 375 &c., in the o- and p-, but not in the m-position. (Cf. Picryl Chloride and Picramide.) The three ni tramlines crystallize in yellow needles or prisms, and are readily soluble in alcohol, but only very slightly in water. They melt respectively at 71, 114, 147, and their acetyl derivatives at 92, 142, and 207. The o- and m-compounds are volatile with steam, but not ^-nitraniline. When reduced, they yield phenylene-diamines. Di- and trinitranilines, C 6 H 3 (N0 2 ) 2 (NH 2 ) and *-C 6 H 2 (NO 2 ) 3 (NH 2 ), are likewise known; the latter, which is termed picramide, and which crystallizes in yellow needles, m.-pt. 188, comports itself as the amide of picric acid, since it is readily transformed into the latter compound on hydrolysis. (For alkyl derivatives, see under Secondary and Tertiary Monamines.) Homologues of Aniline. Of the three toluidines, CH 3 C 6 H 4 NH 2 , the o- and ^-compounds are obtained by the reduction of the corresponding nitro-compounds. The o- is liquid and the p- solid. m-Toluidine, which is liquid, may be prepared from wi-nitro- toluene or ra-nitro-benzaldehyde (cf. B. 15, 2009). The boiling-points of the three isomeric toluidines are almost identical, but the melting-points of their acetyl compounds differ widely (see table, p. 367) ; these are, therefore, of value for the characterization ot the toluidines. o-Toluidine is coloured violet by a solution of bleaching-powder, and blue by sulphuric and nitrous acids and also by ferric chloride, but not >-toluidine. For their conversion into fuchsine, see Triphenyl- methane dyes. If during oxidation the amino-group be pro- tected by the introduction of acetyl, the methyl radical can be oxidized to carboxyl and an acetyl derivative of amino- benzoic acid obtained. When oxidized with KMnO 4 , the amino-compounds are transformed into azo-compounds. (For higher homologues, see table, p. 367.) B. Secondary Monamines We have purely aromatic secondary amines, such as di- phenylamine, (C 6 H 5 ) 2 NH, and mixed secondary bases, which contain both an alphyl and an aryl group, e.g. methylaniline. C tt H 6 .NH.CH 8 . 376 XXI. ARYLAMINES Modes of Formation. 1. Mixed secondary amines are formed when the primary amines are heated with alphyl iodides (Hof- mann) (see p. 105). This reaction does not usually stop short with the intro- duction of one alphyl radical, but extends further with the formation of tertiary bases. In order to avoid this, the alphyl iodide, &c., may be allowed to act upon the acetylated primary bases, e.g. acetanilide [or upon their sodium compounds (Hepp}\ and the resulting acetyl compound hydrolysed : C 6 H 6 .NH.CO-CH 3 -f-CH 3 I = C 6 H 6 .N(CH 3 )CO.CH 3 + HI. The secondary bases are separated from the tertiary by treatment with nitrous acid (see below, under Nitrosamines). 2. The purely aromatic secondary amines are obtained when the primary arylamines are heated with their hydrochlorides : NH 3 . Twodiffsrent aryl radicals maybe introduced, <?.</. (C 6 H 6 )(CH 3 C 6 H 4 )NH, phenyl-tolylamine. Behaviour. 1. The mixed secondary bases have strongly- marked basic properties, while the purely aromatic are feebler bases than the primary arylamines (cf. p. 366). 2. For the migration of the alphyl group from the side chain into the nucleus, see p. 369. 3. The hydrogen of the imino-group is replaceable by an alkyl or acyl radical, and also by potassium or sodium: (C 6 H 6 ) 2 NH + CH 3 I = HI + (C 6 H 5 ) 2 NCH 3 Methyl-diphenylamine. (CeH^H + CCHg-CO^O = CH 3 .CO 2 H + (C 6 H 5 ) 2 N.CO.CH 3 Acetyl-diphenylamine. 4. The secondary bases give neither the isonitrile nor the "mustard oil" reaction (p. 108). 5. With nitrous acid, nitrosamines are formed (cf. p. 108): C 6 H 6 NHCH 3 + NO.OH = H 2 O + C 6 H 6 .N(NO).CH 3 Pheuyl-methyl-nitrosamine. These nitrosamines are neutral oily liquids insoluble in water, and they regenerate the secondary bases when heated with stannous chloride or with alcohol and hydrochloric acid. With mild reducing agents they yield hydrazines. They serve for the preparation of the pure secondary bases, TERTIARY MONAMINES 377 since they alone are precipitated by sodium nitrite as non- basic oils from the acid solution of a mixture of primary, secondary, and tertiary bases. When such nitrosamines are digested with alcoholic hydrochloric acid, a molecular re- arrangement takes place, and compounds of the nature of nitroso-dimethyl-aniline (p. 378) are formed, the nitroso-group becoming attached to a carbon atom of the nucleus (0. Fischer and Hepp, B. 19, 2991; 20, 1247): C 6 H 6 .N(NO).CH 3 = NO.C 6 H 4 .NHCH 3 . All nitrosamines give Liebermann's reaction (p. 409). Methyl aniline, C 6 H 5 -NHMe, is a colourless oil lighter than water. It is a stronger base than aniline; its sulphate does not crystallize, and is soluble in ether. With bleaching-powder it gives a brown coloration. (For the oxidation of ethylaniline, see Bamberger, Abstr. 1902, 1, 275.) Diphenylamine, NHPh 2 , crystallizes in colourless plates, melts at 54, distils at 302, and its solution in sulphuric acid yields an intense blue colour with a trace of nitric acid (deli- cate test). It is prepared by heating aniline and aniline hydrochloride at 210-240. The nitrosamine, NPh 2 -NO, forms yellow plates melting at 6 6 '5, and the acetyl-deriva- tive, NPho-CO-CHg, melts at 103. Numerous nitro-deriya- tives are Jmown, e.g. [C 6 H 2 (N0 2 ) 3 ] 2 NH, which is feebly acidic in properties; its ammonium salt, C 12 H 4 (N0 2 ) 6 NNH 4 , is the dye aurantia. C. Tertiary Monamines These also are either purely aromatic or mixed (alphyl- arylamines). Modes of Fwmation. 1. The latter are formed when the primary or secondary bases are alkylated (cf. p. 376). Methyl bromide, iodide or sulphate are often used on the small scale, but on the manufacturing scale methyl alcohol and hydro- chloric acid under pressure. A convenient laboratory method is that due to Noelting (B. 1891, 24, 563; J. C. S. 1904, 85, 236). The primary amine is heated on the water-bath with a slight excess of the alkyl iodide and sodium carbonate solution, and in many cases an almost theoretical yield of the tertiary amine is formed. Tertiary bases are also formed when the quaternary salts are strongly heated. S?8 XXI. ARYLAMlNtiS 2. Triphenylamine, a purely aromatic base, is formed by the action of bromobenzene upon dipotassium-aniline : C C H 5 NK 2 + 2C 6 H 6 Br = (C 6 H 6 ) 3 N + 2KBr. Behaviour. 1. Unlike the alphyl-arylamines, the purely aro- matic tertiary amines are incapable of forming salts. 2. They do not yield isonitriles with CHC1 3 , isothiocyanates with CS 2 , or acyl derivatives with acid chlorides, but most of them yield quaternary compounds with methyl iodide. 3. Nitrous acid reacts with the tertiary aromatic bases (which thereby differ from the tertiary bases of the fatty series), yielding coloured nitroso-compounds which contain the NO-group linked to the benzene nucleus: C 6 H 6 .N(CH 3 ) 2 + NO.OH = NO.C 6 H 4 .N(CH 3 ) 2 + H 2 O. 2>-N itroso-d imethyl-aniline Such nitroso- derivatives are, in contradistinction to the nitrosamines already mentioned, converted into diamines on reduction, and when hydrolysed yield nitroso-phenols. 4. The tertiary amines, when oxidized with hydrogen per- oxide, yield unstable oxides, e.g. dimethyl-phenylamine oxide, CgHg'NMeolO, feebly basic compounds soluble in water, and decomposed at high temperatures. (B. 1899, 32, 346; Abstr. 1901, 1, 200.) 5. Tertiary amines in which the three substituents are different, e.g. methyl-ethyl-aniline or benzyl-phenyl-hydrazine, do not exist in isomeric forms, and cannot be resolved into optically active components (Kipping and Salway, J. C. S. 1904, 438; H. 0. Jones and Millington, C. C. 1904, 2, 952). The centres of gravity of the nitrogen atom and of the three sub- stituents would therefore appear to lie in one plane. Dimethyl-aniline, C 6 H 5 N(CH 3 ) 2 , is an oil of sharp basic odour, solidifying in the cold; its salts do not crystallize well. It combines with methyl iodide, even in the cold, to the com- pound N(C 6 H 5 )(CH 3 ) 3 I, phenyl-trimethyl- ammonium iodide, which breaks up into its components when distilled. With nitrous acid it yields ^-nitroso-dimethyl-aniline, which crystal- lizes in green plates, melting at 85; the hydrochloride crys- tallizes in yellow needles. When oxidized with permanganate the nitroso-compound yields ^-nitro-dimethyl-aniline (m.-pt, 162), when reduced ^-amino-dimethyl-anilme, and when hy- drolysed with alkali ^-nitroso-phenol (p. 412) and dimethyl- THE QUATERNARY BASES 379 amine. (For condensations, see Malachite green, p. 483.) Bleaching-powder colours dimethyl-aniline only a pale-yellow. Dimethyl-aniline yields compounds of somewhat complex com- position with acid chlorides, aldehyde, &c.; for example, tetra- methyl-diamino-benzophenone or, finally, methyl violet with carbonyl chloride, leuco-malachite green with benzoic alde- hyde, &c. Mild oxidizing agents, such as chloranil, convert it into methyl violet. Diethyl-aniline boils at 213; its nitroso-derivative melts at 84. Triphenyl-amine, NPh 3 , melts at 127, and yields no salts. D. The Quaternary Bases correspond entirely with the quaternary bases of the fatty series. Trimethyl-phenyl-ammonium hydroxide, C 6 H 5 N(CH 3 ) 3 OH, for instance, is a colourless, strongly alkaline, bitter substance which breaks up into dimethyl -aniline and methyl alcohol when heated. Most of the tertiary amines, however, which contain substituents in the two ortho- positions with respect to the alphylated NH 2 group, are incapable of yielding quater- nary ammonium salts, e.g. : N(CH 3 ) 2 (E. Fischer, B. 1900, 33, 345, 1967). This is an example of steric retardation or inhibition (cf. p. 175). The readiness with which a given quaternary salt is formed depends to a large extent on (a) the order in which the radicals are introduced, (6) the nature of the alkyl haloid used, e.g. chloride bromide or iodide, the last reacting most readily, (c) the solvent (p. 106), and (d) temperature (cf. Wede- kind, A. 1901, 318, 90; Jones, B. A. Kep. 1904, 179). It has been found that in the preparation of phenyl-dimethylethyl ammonium iodide a 100 -per -cent yield is obtained when methylethyl-aniline is combined with methyl iodide, but only a 15-per-cent when dimethyl -aniline is combined with ethyl iodide under similar conditions. 380 XXI. ARYLAMINES E. Diamines, Triamines, &c. Polyamino-derivatives may be obtained by reducing poly- nitro-hydrocarbons or nitro-amino-compounds, e.g. : C 6 H 4 (N0 2 ) 2 * C 6 H 4 (NH 2 ) 2 (plienylene-diamine). The o- and ^-diamines are best obtained from the o- and p-nitro-amino-compounds. Tetramino- benzene is formed in an analogous manner by reducing dinitro-m-diamino-benzene. A new amino-group can be introduced in the ^-position into an arylamine, especially a secondary or tertiary, such as C 6 H 5 N(CH 3 ) 2 , by first transforming the latter into an azo- dye (e.g. benzene-azo-dimethyl-aniline, C 6 H 6 -N:NC 6 H 4 NMe) by coupling it with benzene-diazonium chloride, and decom- posing this by reduction. (See the Azo-compounds.) Diamines are also formed by the reduction of the nitroso- compounds of tertiary amines; amino-dimethyl-aniline, NH 2 - CglBL-N^Hg)^ from ^-nitroso-dimethyl-aniline. The polyamines are solid compounds which crystallize in plates and distil unchanged, and are soluble in warm water. Though originally without colour, most of them quickly become brown in the air, their instability increasing with the number of amino-groups present. In accordance with the readiness with which they are oxidized, they frequently yield characteristic colorations with ferric chloride, e.g. 0-phenylene- diamine a dark-red, and 1 : 2 : 3-triamino-benzene a violet and then a brown colour. The three isomeric groups of diamines differ materially in their behaviour: (a) Ortho-cLLamines. 1. Ferric chloride yields a yellowish-red crystalline precipitate of diamino-phenazine hydrochloride with a solution of o-phenylene-diamine. 2. The mono-acyl compounds of the o-diamines change into derivatives of imido-azole (A. 273, 269), the so-called "JBenz- imido-azoles " or " Anhydro-lases ", through the formation of in- tramolecular anhydrides; thus o-nitracetanilide, when reduced with tin and hydrochloric acid, yields methyl-benzimido-azole or phenylene-ethenyl-amidine (A. 209, 339): Compounds of this nature are also obtained by heating o-diamines with acids. ACYL DERIVATIVES 381 3. Glyoxal and many of the a-diketones yield qumoxaline and its derivatives with 0-diamines : ON;n a ""o;c.R N;H 2 OJC-R and the a-ketonic alcohols react in an analogous manner, e.g. benzoin yields dihydro-diphenyl-quinoxaline. 4. Nitrous acid converts the o-diamines into the so-called ." azimido-compounds ", compounds which contain three atoms of nitrogen, e.g. 0-phenylene-diamine into azimido- benzene = imido-azo-phenylene, CgH^^N (B. 9, 219, 1524; 15, 1878, 2195; 19, 1757). (b) Meta-diamino-bases. 1. These form yellow-brown dyes with nitrous acid, even when only traces of the latter are present. (See Bismarck Brown, p. 401). 2. They yield azo-dyes with benzenediazonium chloride (see Chrysoidine, p. 401.) 3. With nitroso-dimethyl-aniline, or on oxidation together with para-diamines, blue colouring-matters (indamines) are ob- tained, and these when boiled yield red dyes (see Toluylene red). (c) Para-diamino-compounds. 1. When warmed with ferric chloride, or better, with Mn0 2 + H 2 S0 4 , quinone, C 6 H 4 2 (or a homologue), is formed, and may be recognized by its odour. 2. By oxidizing para-diamines, containing one amino-group, together with a monamine or a meta-diamine, indamines are produced. ACYL DERIVATIVES OF ABYLAMINES. ANILIDES, &c. Practically all primary and secondary arylamines but not tertiary react with acids, or better, acid anhydrides or acid chlorides, yielding acyl derivatives, the most characteristic of which are the acetyl derivatives, e.g. C 6 H 5 NH CO CH 3 , CH 3 .C 6 H 4 .NH.CO.CH 3 , (C 6 H 5 ) 2 N CO . CH 3 , &c. The acyl products formed from aniline are termed anilides (p. 370), e.g. acetanilide, benzanilide, oxanilide; they are really phenylated acid amides (see p. 182 et seq.), and as such may be hydrolysed, although not so readily as the amides, by means of acids or alkalis, to aniline and the corresponding acid. The dibasic acids like oxalic acid can give rise not merely to anilides, e.g. C 6 H 5 .NHCO.CO.NH.C 6 H 5 , oxanilide, but 382 XXI. ARYLAMINES also to half anilides, the anilic acids, which correspond with the amic acids, e.g. oxanilic acid, C 6 H 5 NH CO CO OH. These are monobasic acids, and can also be hydrolysed to their components. Similarly, the toluidines give rise to toluidides, e.g. acetolui- dide, CH 3 .C 6 H 4 .NH.CO.CH 3 , the xylidines to xylidides, &c. The acetyl derivatives are frequently used for the identi- fication of the various primary and secondary arylamines, since they crystallize well and have definite melting-points. As a rule, it is sufficient to mix the amine with a slight excess of acetic anhydride and warm for two minutes, and then to pour into water. After a short time the solid (or oily) acetyl derivative is obtained. Formanilide, C 6 H 6 NHCH:0, from aniline and formic acid, is worthy of note, because its sodium salt reacts accord- ing to the formula C 6 ILNNaCH:0, but its silver salt ac- cording to the formula C 6 H 5 N : CH Ag. (Cf. B. 23, 2274, Ref. 659.) The latter corresponds to those isomers of the amides, the imido-hydrates and imino-ethers (p. 187). Acetanilide, C 6 H 5 NHCO'CH 3 , is most conveniently pre- pared by boiling aniline with glacial acetic acid for twenty- four hours. It crystallizes in beautiful white prisms which are readily soluble in hot water or alcohol, less readily in ether and benzene. It melts at 115, and boils at 304. In the absence of water it can form a hydrochloride, C 7 H 9 ON, HC1. Acetanilide is used, under the name of " antif ebrine ", as a medicine in cases of fever. Thio-acetanilide, C 6 H 5 NH.CS.CH 3 , is formed when acet- anilide is heated with P 2 S 5 , and from it imido-thio-com- ponnds, amidines, &c., can be prepared. Methyl-acetanilide, C 6 H 5 .N(CH 8 )(CoH 3 0), is used as a specific against headache. Oxanilide, C 6 H 5 - NH . CO . CO NH . C 6 H 5 , is obtained when aniline oxalate is heated at 160-180. It melts at 252, boils without decomposition, and is best hydrolysed by fusion with potash. The half anilide, oxanilic acid, COOH CO NH C 6 H 5 , is formed when aniline oxalate is heated at 130-140. It melts at 149-150, is soluble in hot water, has the properties of a monobasic acid, and with phosphorus pentachloride yields phenyl carbimide (phenyl isocyanate): C 6 H 6 .NH.CO.OH C 6 H 6 .NH.CO.C1 C 6 H 5 .N:C:O. Diacyl derivatives of aniline and its homologues are also DIACETANILIDE. PRIMARY AMINES 383 known, e.g. C 6 H 5 N(CO CH 3 ) 2 , diacetanilide. This is formed, together with acetanilide, when aniline is boiled for an hour with excess of acetic anhydride, or when the amine is heated to a high temperature with acetyl chloride. The two may be separated by fractional distillation under diminished pressure. The diacetanilide crystallizes in colourless prisms, melts at 37, and, unlike acetanilide, is readily soluble in benzene or light petroleum. On hydrolysis with dilute alkali, one acetyl group is split off more readily than the second. The presence of one or two substituents in the o-position with respect to the amino-group of aniline facilitates the for- mation of diacetyl derivatives, e.g. o-toluidine yields a diacetyl derivative more readily than aniline, and s-tribrom-aniline yields a diacetyl derivative with the greatest readiness (J. C. S. 1901, 533). In nearly all those compounds of the fatty series which are amino- or imino-derivatives of alcohols, acids, or hydroxy- acids, the unreplaced ammoniacal hydrogen can be substituted indirectly either wholly or partially by phenyl. The number of these phenylated (tolylated, xylylated, &c.) compounds is thus extremely large. Among them may be mentioned: Phenyl-glycocoll, Phenyl-glydne, C 6 H 5 - NH . CH 2 . C0 2 H, from chloracetic acid and aniline; phenyl-imino-butyric acid, CH 3 C(:NCgH 5 )-CH. 2 -C0 2 H, from aniline and aceto-acetic ester; carbanilide or diphenyl-urea, CO(NHC 6 H 5 ) 2 , from aniline and carbon oxy chloride (cf. p. 280); phenyl isocyanate, phenyl carbimide, COiN-CgHg, from COC1 2 and fused aniline hydro- chloride, a sharp-smelling liquid exactly analogous to the iso- cyanic esters its vapour gives rise to tears; phenyl isothio- cyanate, C 6 H 5 N:CS (b.-pt. 222), a liquid possessing all the characteristics of the mustard oils (p. 275); diphenyl thio- urea, CS(NHC 6 H 6 ) 2 , from aniline and carbon disulphide (forms glistening plates, melting at 154; it is decomposed into phenyl isothiocyanate and aniline when hydrolysed with concentrated HC1). PRIMARY AMINES WITH THE AMINO-GROUP IN THE SIDE CHAIN These compounds resemble the primary alphylamines much more closely than aniline. As an example, we have benzyl- amine, C 6 H 5 CH 2 NH 2 , the amine corresponding with benzyl alcohol; it is a colourless liquid which distils un- changed. The acetyl compound, C 6 H 5 .CH 2 .NH-CO.CH 2 , 384. XXII. DIAZO- AND AZO-COMPOUNDS is formed by heating benzyl chloride, CpH 5 CH 2 Cl, with acet- amide. Benzylamine is formed, together with di- and tri- benzylamines, by the action of alcoholic ammonia on benzyl chloride; it is also readily obtained by reducing the phenyl- hydrazone of benzaldehyde : C 6 H 6 .CH:N- NHC 6 H 6 - H H 2 i H It may also be prepared from benzyl chloride and potassium phthalimide (cf. p. 465). Its behaviour is entirely analogous to that of methylamine, as the phenyl derivative of which it is to be regarded. It dissolves in water, and the solution thus formed is alkaline. Conductivity determinations show that it is about as strong a base as ammonia, and thus differs materi- ally from aniline. It possesses all the characteristic properties of a primary amine, but as the NH 2 is attached to a side chain and not to the benzene nucleus it cannot be diazotized, and on treatment with nitrous acid it immediately yields benzyl alcohol. XXII. DIAZO- AND AZO-COMPOUNDS; HYDEAZINES A. Diazo-eompounds The primary arylamines differ characteristically from the primary alphylamines in their behaviour towards nitrous acid. The latter are converted into alcohols without the formation of intermediate products (cf. p. 108): The aromatic amines can undergo an analogous transfor- mation; but if the temperature is kept sufficiently low, well- characterized intermediate products, the so-called diazo-eom- pounds or diazonium salts, e.g. benzene diazonium chloride, C 6 H 5 N 2 C1, are obtained, which are of especial interest both scientifically and technically (cf. Azo-dyes, p. 389). They were discovered by P. Griess in 1860, and were carefully investigated by him (A. 121, 257; 137, 39). The diazo-compounds are usually divided into (1) the diazo- r^ FT nium salts, e.g. 6 p>NjN, compounds which are analogous DIAZONIUM COMPOUNDS <385 to ammonium salts; (2) the true diazo-compounds, which con- tain the grouping N : N . I. Diazonium Compounds, The diazonium salts, as a rule, #re not obtained in the solid state, as they themselves are of little commercial value, but are of importance as intermediate products in various decompositions. Solutions are usually prepared by the addition of an aqueous solution of sodium nitrite to a solution of the amine in an excess of the requisite acid (V. Meyer}. The essentials are (1) The solution must be kept cool, at or only a few degrees above, otherwise a phenol is formed and nitrogen evolved. (2) An excess of acid must be used, otherwise diazo-amino-compounds are formed. (3) As a rule, it is advisable not to use an excess of nitrous acid. This is avoided by testing for free nitrous acid by means of potassium iodide starch paper. This conversion of amino- into diazo-compounds is termed " diazotizing ". The crystalline salts, e.g. benzene-diazonium chloride, may be obtained by adding concentrated hydrochloric acid to an alcoholic solution of aniline hydrochloride, and then amyl nitrite (Knoevenagel). They may also be obtained by the addition of alcohol and ether to their aqueous solutions. Constitution. The N. 2 X group can be attached to only one carbon atom of the benzene nucleus, since (1) when the salts undergo decomposition the products formed contain groups, e.g. Cl, OH, CN, &c., which are attached to a single carbon atom; (2) penta- substituted anilines, e.g. S0 3 H-C 6 Br 4 NH 2 , can be diazotized, hence Griess' formulae, e.g. C 6 H 4 N 2 , HC1, where the diazo-radical replaces two hydrogen atoms of the nucleus, are untenable. For many years the constitutional formula given to these compounds was that suggested by KekuU, viz. C 6 H 5 *N:NC1, for the chloride; this represents them as analogous to the azo-compounds. This formula readily explains the reduction of the diazonium salts to hydrazines, CVH 5 NHNH 2 , and their conversion into azo-dyes, e.g. C 6 H 5 N : N C 6 H 4 OH. Within the last few years a constitutional formula which was suggested by Blomstrand in 1875 has become generally accepted. This repre- sents the molecule of a diazonium salt as containing a quinque- O TT valent nitrogen atom, e.g. 6 Q->N:N. The chief arguments in favour of the Blomstrand formula are briefly: (B480) 2P, 386 XXII. DIAZO- AND AZO-COMPOtTNDS 1. It indicates the resemblance between the diazonium and ammonium salts, as both thus contain quinquevalent nitrogen : and The resemblance between the two groups of compounds is marked. The diazonium salts are colourless crystalline com- pounds readily soluble in water; those derived from strong acids, e.g. the chlorides, nitrates, and sulphates, are neutral in solution, cf. NH 4 C1; whereas those derived from feeble acids, e.g. carbonic acid, are partially hydrolysed in aqueous solution, and hence give an alkaline reaction, cf. Na.,C0 8 or (NH 4 ) 2 C0 3 . In addition they form sparingly soluble platinichlorides, (C 6 H 5 N 2 ) 2 PtCl 6 , and aurichlorides, C 6 H 5 N 2 AuCl 4 , comparable with the ammonium compounds. The aqueous solutions of the salts are ionized to much the same extent as the corre- sponding quaternary ammonium salts. This resemblance of the diazonium ions to the quaternary ammonium ions is further established by a comparison of migration values. The free base, benzene -diazonium hydroxide, corresponding with ammonium hydroxide, is obtained by the action of moist silver oxide on the chloride; it dissolves readily in water, yielding strongly alkaline solutions, but is very unstable, and gradually decomposes. When neutralized with acids, it yields the above-mentioned diazonium salts. 2. The conversion of aniline and its homologues into diazo- nium salts is rendered somewhat more simple by such a for- mula: HO 3. The elimination of nitrogen and the formation of mono- Bubstituted compounds, e.g. C 6 H 5 -OH, C 6 H 6 Br, &c., is readily explicable: Cain (J. C. S. 1907, 91, 1049) has suggested a new consti- tutional formula for diazonium salts, e.g. benzene-diazonium chloride, :N.C1 -N is claimed that the double linkage between nitrogen and REACTIONS OP DIAZONIUM SALTS 387 carbon atom of the benzene nucleus is more in harmony with the readiness with which the nitrogen is eliminated from the molecule. It also accounts for the fact that in a ^-diamine only one amino-group can be diazotized. Reactions. 1. The reaction characteristic of the diazonium salts is the readiness with which nitrogen is eliminated and monovalent groups introduced into the molecule in place of the N 2 X radical, and for this reason the diazonium compounds are frequently made use of in the laboratory for the prepara- tion of various substituted benzene derivatives. As examples of this type of reaction, we have (a) Replacement of N 2 X by OH. An aqueous solution of a diazonium salt, especially one containing sulphuric acid, evolves all its nitrogen in the form of gas when warmed, and a phenol is formed : |N:N = Cfl H 6 .OH + N 2 -f HCI. This reaction, which is of very universal application, there- fore allows of the exchange of NH 2 for OH. The only excep- tions appear to be those salts containing numerous negative substituents in the benzene nucleus, e.g. C 6 H 2 Br 3 N 2 C1. For the effect of light on the decomposition of solutions of diazonium salts, see Orton, Coates, and Burdett, P. 1905, 168. (b) Replacement by H. When diazonium-compounds, either in the solid state or dissolved in concentrated sulphuric acid, are heated to boiling with absolute alcohol, the diazo-group is generally replaced by hydrogen. In this reaction the alcohol gives up two hydrogen atoms, and is oxidized to aldehyde : This affords a simple method for the replacement of NH by H. Instead of this reaction, there occurs in many cases an ex- change of the diazo-group for the ethoxy-radical,*0'C 2 H 5 , with the formation of ethyl ethers of phenols; thus from chlorinated toluidines ethyl ethers of chloro-cresols are formed, and not chloro-toluenes (B. 17, 2703; 22, Ref. 658; 34, 3337). Under certain conditions stannous chloride in alkaline solu- tion acts in an analogous manner (B. 22, Ref. 741), while under others it gives rise to hydrazines (p. 397). In 388 XXII. DIAZO- AND AZO-COMPOUNDS manner NH 2 may be replaced by H, by first converting an amino-compound into a hydrazine, and then decomposing the latter with CuS0 4 (Baeyer, B. 18, 89). (c) Replacement by Halogen Sandmeyer's Reaction. When a diazonium-compound is warmed with a concentrated solution of cuprous chloride in hydrochloric acid, the diazo-group is replaced by chlorine (Sandmeyer, B. 17, 1633; 23, 1218, 1628; A. 272, 143). The same reaction takes place on distilling the diazonium platinichloride with soda, and sometimes on simply treating the diazo-compound itself with fuming hydrochloric acid, or with hydrochloric acid in presence of copper dust (Gattermann) : Warming with cuprous bromide yields, in the same way, a bromo-derivative (Sandmeyer, B. 18, 1482), and treatment with hydriodic acid or potassium iodide an iodo-compound : 2C 6 H 6 .N 2 .C1 + CuJBro = 2C 6 H 5 Br + Cu 2 CL + N 2 ; C 6 H 6 N 2 Cl + KI = C C H 5 I + KC1 + N 2 . The ammo-group may further be exchanged for bromine by boiling the diazonium perbromides (see Benzene-diazonium per- bromide) with absolute alcohol. (d) ^Replacement by C]N. This is accomplished by adding the diazotized solution to a warm solution of potassium cuprous cyanide : C 6 H 6 .N 2 C1 C 6 H 6 N 2 CN C 6 H 5 -CN. This reaction is of importance, as the product obtained is a nitrile, and can be hydrolysed to an acid. (e) Phenyl sulphide is formed by the action of hydrogen sulphide on benzene-diazonium chloride (cf. B. 15, 1683); nitro- benzene is formed by the action of nitrous acid in presence of cuprous oxide; benzenesulphonic acid from sul- phurous acid; phenyl thiocyanate from thiocyanic acid; and phenyl cyanate from cyanic acid, &c. (cf. B. 23, 738, 1218, 1454, 1628; 25, 1086; 26, 1996). (/) When oxidized in alkaline solution, benzene-diazonium hydroxide yields together with other products nitroso-ben- zene (p. 365), and much benzene-diazoic acid, C 6 H 5 'N -NO- OK, or its isomeride, phenyl - nitramine, C 6 H 5 NHNO,, (m.-pt. 46; explodes at 98) (see B. 26, 471; 2?, 584, 915). REACTIONS OF DIAZONIUM SALTS 389 2. When a solution of a diazonium compound reacts with a primary or secondary amine, or when nitrous acid acts upon such an amine in the absence of free mineral acid, diazo- amino-compounds are formed, and these readily change into amino-azo-compounds : Diazo-amiuo-benzene. 3. Azo-dyes. The diazonium salts readily react with ter- tiary amines or with phenols, yielding derivatives of azo- benzene, e.g. : C 6 H 6 .N 2 C1 + C 6 H 6 N(CH 3 ) 2 = HC1 + C 6 H 6 .N:N.C 6 H 4 .N(CH 3 ) 2 Dirnethyl-amino-azobenzene. C 6 H 6 .N 2 C1 + C 6 H 5 .OH = HC1 + C 6 H 5 -N:N.C 6 H 4 .OH Hydroxy-azobenzene. Such derivatives possess basic or acidic properties, are usually coloured yellow, red, or brown, and are known as azo-dyes. The formation of such an azo-dye is largely made use of as a test for a primary aromatic amine with the NH 2 in the nucleus. The amine is dissolved in acid, diazotized, and then mixed with an alkaline solution of a phenol (preferably /3-naphthol), when an orange-red dye is precipitated. The process is commonly spoken of as the "coupling" up of a diazonium salt with an amine or a phenol. It has been proposed to use diazo-compounds, sensitive to light, in photography (B. 23, 3131; 34, 1668). 4. The diazonium salts react in alkaline solution with com pounds containing the grouping CH 2 'CO, yielding azo-com- pounds or phenylhydrazones, e.g. : PIT rn PTT rn ^ /H3C Cf. B. 1888, 21, 1697. For the azo or hydrazone constitution of such compounds, compare Auwers (Abstr. 1908, i, 477; 1911, i, 168, 585). Benzene-diazonium perbromide, C 6 H 5 N 2 Br, Br 2 , is a dark- brown oil, solidifying to yellow crystalline plates, and is pre- pared by the addition of HBr or KBr and bromine water to diazonium salts. Two of its atoms of bromine are only loosely linked. Ammonia converts it into benzene-diazo-imide, which 390 XXII. DlAZO- AND A20-COMPOtJN&S is to be regarded as the phenyl derivative of hydrazoic acid, N 3 H, thus: C 6 H 6 N(Br) : N + Br 2 = C 6 H 6 NBr 2 : NBr [Beuzene-diazonium perbromide]. a XT [Benzene-diazo-imide]. In accordance with this, dinitro-benzene-diazo-imide (from dinitro-aniline) is decomposed by alcoholic potash into dinitro- phenol and hydrazoic acid a method of obtaining this latter substance by means of organic compounds (see p. 298). II. Diazo- compounds. These contain the grouping R-N: NX, where R = an aryl radical and X an acid radical or OH or OK. When a benzene-diazonium salt is mixed with an excess of alkali, a potassium salt, normal potassium diazo- benzene oxide, C 6 H 5 N 2 OK, is precipitated. It crystallizes in white plates, and can be quantitatively converted into ben- zene-diazonium chloride; it yields ethers, and on oxidation gives nitroso-benzene and benzene-diazoic acid: C 6 H 6 .N:N< H or CflH^NH-NOj, The acid, C 6 H 5 N 2 OH, which corresponds with the potassium salt, is not known in a pure form. When the normal potas- sium salt is heated with concentrated potash at 130-135, it is transformed into potassium isodiazo-benzene oxide (Schraube and Schmidt, B. 1894, 27, 520). When this is acidified with acetic acid, the free hydroxide is obtained as a colourless oil which is very unstable. Similar normal and isopotassium derivatives have been ob- tained from other diazonium salts, and it has been found that the presence of negative radicals (Br, N0 2 ) facilitates the for- mation of the iso-compound, in fact to such an extent that certain diazonium salts, when added to an alkali, immediately yield the isodiazo-compounds. Considerable controversy has taken place regarding the constitutional formulae of these two groups of compounds. At one time the isodiazo-oxides were regarded as derivatives of phenyl-nitrosamine, viz. C 6 H 5 -NK NO, and the normal compounds as true diazo-oxides, C 6 H 6 N:NOK. The researches of Hantzsch have proved that the two compounds are very similar as regards chemical properties. For example, both "couple" with alkaline solutions of phenols, yielding azo-dyes (p. 389), but as a rule the normal more readily than the iso-compounds. Both compounds, on reduc- STEREO-ISOMERIC DIAZO-HYDROXtDES 391 tion with sodium amalgam in the presence of a large excess of alkali, yield phenyl-hydrazine, and both compounds, on oxi- dation in alkaline solution, yield potassium benzene-diazoate, C 6 H 5 N : NO OK. Similarly, both compounds yield the same benzoyl derivative by the Schotten-Baumann method. Hantzsch draws the conclusion that the two compounds are structurally identical and stereo-isomeric. As the w-diazo-oxide can be syn- thesised by the action of hydroxylamine on nitroso-benzene in alkaline solution (B. 38, 2056): N.OH = H 2 + C 6 H 6 .N:N-OH, it is probable that both normal and iso-compound are true diazo-derivatives, and that they are stereo-isomeric in much the same manner as the oximes (p. 138). According to Hantzsch, the normal compound has the syn- and the iso- the <w&'-configuration : C 6 H 5 -N C 6 H 6 .N KO-N N-OK, Potassium benzene syn diazo-oxide anti as the normal compounds evolve nitrogen very readily, whereas the iso-compotinds are more stable. (Ber. 1894, 27, 1702; 1895, 28, 676, 1734; 36, 4054; 37, 1684.) The isodiazo-oxides can almost undoubtedly react as tauto- meric compounds, viz. as nitrosamine derivatives, C 6 H 5 -NK NO, since the potassium salt yields an N-ether, C 6 H 5 'NEt-NO, whereas the silver salt yields an O-ether, C 6 H 5 N : N OEt. Bamberger has suggested that the normal diazo-oxides may have a diazonium constitution C 6 H 5 N(OK)jN, whereas the iso-compound has the diazo-constitution C 6 HgN:NOK; but Hantzsch has pointed out that the diazonium hydroxides, from which the true diazonium salts are formed, must be extremely strong bases, and could not possibly therefore pos- sess sufficiently acidic properties to give rise to stable potas- sium salts which are only partially hydrolysed in aqueous solution. Certain diazo-hydroxides, RN 2 OH, have been isolated as colourless solids with acidic properties ; the majority, however, are extremely unstable, and pass over into the isomeric nitros- amines R-NH-NO, yellow compounds with neutral properties (B. 35, 2964; 36, 4054; 37, 1084). Corresponding with the normal and isodiazo-oxides, Hantzsch 392 XXII. DIAZO- AND AZO-COMPOUNDS has discovered two groups of sulphonates and of cyanides, which he also regards as being stereo-isotneric in the same sense, e.g.: E-N K-N In the case of j0-anisidine, evidence of the existence of three isomeric diazo-cyanides has been obtained. The one is colour- less and is an electrolyte, and hence is regarded as the diazo- nium salt, OMe-C 6 H 4 -N(CN)jN; the other two are reddish- coloured solids and non-electrolytes. The syw-compound is unstable, and melts at 51; it gradually passes over into the more stable an ^'-compound, which melts at 121. It is probable that when a syn diazo-cyanide is dissolved in water it is largely transformed into the ionized diazonium cyanide : Compare also Armstrong and JRobertson, J. C. S. 1905, 1280; Hantzsch, P. 1905, 287. An account of the chemistry of diazo- compounds will be found in B. A. Rep. 1902, 181 (G. T. Morgan), and in Ahrens Sammlungt 1902, 8, pp. 1-82 (Hantzsch). B. Diazo-amino-eompounds The diazo-amino-compounds are pale-yellow crystalline sub- stances which are stable in the air, and do not combine with acids. They are obtained by the action of a primary or secondary amine on a diazonium salt, and also when nitrous acid reacts with a free primary aromatic amine instead of with its hydrochloride, probably : C 6 H 5 NH 2 -f-O:N.OH = C 6 H 6 -N:N.OH + H 2 O and C 6 H 5 .N:N.OH + C 6 H 6 NH 2 = C 6 H 6 .N:N.NHC 6 H 6 + H 2 O. Diazo-amino compounds have been synthesised by the action of Grignard compounds on alkyl or acyl derivatives of hydra- zoic acid, and decomposing the products with water: RN 3 + B'Mgl RN(MgI)-N:NR' RN(MgI).N:NR' + H 2 O R-NH-NiN-R' + Mgl-OH In this manner not merely aromatic but aliphatic aromatic blAZO-AMINO-COMPOtJNDS 393 Compounds of the types C 6 H 6 -NH.N:N.CH 3 and C 6 H 5 CH 2 - NH N : N CH 3 have been prepared. Reactions. 1. They are not bases, and hence do not form salts with acids. 2. They behave in much the same way as the diazo-com- pounds, since they are usually decomposed in the first instance into their components, a diazonium salt and an amine, the former then entering into reaction. Thus diazo-amino-ben- zene, for example, yields phenol and aniline when boiled with water or hydrochloric acid, while with hydrobromic acid it gives bromobenzene and aniline. These reactions are easy to recognize from the accompanying evolution of nitrogen. 3. By the renewed action of nitrous acid in acid solution they are completely transformed into diazonium salts: C 6 H 6 .N 2 .NH.C 6 H 5 + NO 2 H + 2HC1 = 2C 6 H 5 .N 2 .C1 + 2H 2 O. 4. Most of them readily undergo molecular transformation into the isomeric amino-azo-compounds (KekuU): C 6 H 6 .N:N-NH/ \H C 6 H 6 .N:N/ This molecular rearrangement takes place most readily in presence of an amine hydrochloride, which acts as a catalytic agent. The amino-group always takes up the para-position with regard to the azo-group (N:N) if this is free. If, how- ever, this is already substituted, as in the diazo-amino-com- pound from |?-toluidine, then the transformation occurs much more slowly, and the NH 2 takes up the o-position with respect to the N : N group. The velocity of transformation has been investigated by H. Goldschmidt, and the reaction has been shown to be unimolecular. Only a relatively small amount of aniline salt is required, and the velocity is proportional to the strength of the acid, the aniline salt of which is used (B. 1896, 29, 1899). For similar transformations, see Benzidene (p. 395) and Azoxy-benzene (p. 395). 5. The imino- hydrogen of the diazo-amino-compounds is replaceable by metallic radicals, and also by acyl groups. Constitution. By the action of benzene-diazonium chloride upon ^-toluidine, " diazo-benzenef>-toluidide " is formed, and would appear to possess the formula: (I). 394 XXII. DIAZO- AND AZO-COMPOUNDS But the same compound is also obtained from a mixture of ^-toluene-diazonium chloride and aniline, a reaction which would indicate its constitution to be: C 6 H 6 .NH.N:N.CVH 7 (II). It is all the more difficult to decide which of these two formulae is the right one, from the fact that most of those " mixed diazo-amido-compounds " react as if they had both of the above constitutions. Thus, when the compound just men- tioned is boiled with dilute sulphuric acid, it yields not only phenol and ^-toluidine (according to I), but also aniline and ^?-cresol (according to II). Such diazo-ami no-compounds are thus typical tautomeric substances. (Cf. e.g. B. 19, 3239; 20, 3004; 21, 548, 1016, 2557; J. C. S. 1889, 55, 412, 610, &c.) Diazo-amino- benzene, C 6 H 5 N : N NHC 6 H 5 (Griess), is usually prepared by adding NaN0 2 (1 mol.) to the solution of aniline (2 mols.) in HC1 (3 mols.), and saturating with sodium acetate (B. 1884, 17, 641; 1886, 19, 1952). It crystal- lizes in bright-yellow lustrous plates or prisms, is insoluble in water, but readily soluble in hot alcohol, ether, and benzene, melts at 98, and is far more stable than the diazo-compounds. C. Azo-compounds, and Compounds intermediate between the Nitro- and Ammo-compounds While the reduction of nitro-compounds in acid solution leads to the aromatic amines, the use of alkaline reducing agents, such as sodium amalgam, zinc dust and caustic soda, and also potash and alcohol, gives rise for the most part to intermediate products, the azoxy-, azo-, and hydrazo-compounds : C 6 H 5 .N0 2 C 6 H 6 .iST.N.C 6 H 5 C 6 H 5 .N:N.C 6 H 5 Nitro-benzene \/ Azo-benzene Azoxy-benzene C C H 6 NH NHC 6 H 5 C 6 H 6 . NH 2 ; Hydrazo-benzene Aniline and reduction in neutral solution yields pheriyl-hydroxyl- amines, C 6 H 5 -NH.OH. Of these the azo-compounds are the most important 1. AZOXY-COMPOUNDS The azoxy-compounds are mostly yellow or red crystalline substances which v are obtained by the action of alcoholic HYDRAZO-COMPOtlNDS 396 potash, and especially of potassium methoxide (B. 15, 865), upon the nitro-compounds. Many of them may also be obtained by the oxidation of azo-compounds. They are of neutral reaction, and are very readily reduced to azo-com- pounds. Azoxy - benzene, (C 6 H 5 ) 2 N 2 (Zinin), forms pale -yellow needles melting at 36, is insoluble in water, but dis- solves readily in alcohol and ether. Concentrated sulphuric acid transforms it into the isomeric ^?-hydroxy-azo-benzene, C G H 5 N:N.C 6 H 4 .OH. 2. HYDRAZO-COMPOUNDS These are colourless crystalline neutral compounds, and, like the azo-compounds, cannot be volatilized without decom- position; e.g. hydrazo- benzene decomposes into azo-benzene and aniline when heated. They are obtained by the reduction of azo-compounds with ammonium sulphide or zinc dust and alkali, or by sodium hyposulphite. Oxidizing agents, such as ferric chloride, readily transform them into azo-compounds, a reaction which also occurs when the hydrazo-compounds are exposed to the air. Stronger reducing agents, e.g. sodium amalgam, convert them into amino-compounds. Strong acids cause them to change into the isomeric deriv- atives of diphenyl (p. 472); thus from hydrazo-benzene and hydrochloric acid we obtain benzidine hydrochloride (the hydrochloride of ^/-diamino-diphenyl, p. 472): > NIL, This rearrangement is typical, and is often observed in the case of aromatic compounds. It may be regarded as the shifting or wandering of a radical in this case the relatively complex CgH 5 NH from attachment to the side chain to direct attachment to the benzene nucleus, or, in other words, the NH'CgHg group exchanges place with the hydrogen atom in the ^-position in the nucleus: 396 XXII. DIAZO- AND AZO-COMPOUNDS The operation is repeated, and j^'-diamino-diphenyl is formed. Other well-known examples of this are the transformation of methyl-aniline or dimethyl-aniline into o-toluidine and xylidene, and ultimately into mesidene (Hofmann, p. 368); the transforma- tion of N-brominated amines or anilides, e.g. C 6 H 5 NBr COCH 3 into C 6 H 4 Br-NH.COCH 3 (Chattaway and Orion, p. 370), of dia- cetylated amines, C 6 H 5 N(COCH 3 ) 2 , into ketonic substances, CH 3 CO - C 6 H 4 NH - CO CH 3 (Chattaway, J. C. S. 1 904, 386, 589, 1663), of phenyl-hydroxylamine into ^-amino-phenol (p. 395), and of diazo-amino-benzene into amino-azo-benzene (p. 391). This molecular rearrangement does not take place if the hydrogen which occupies the para-position to the imino-group is replaced by other groups. In such cases a partial re- arrangement only occurs, and derivatives of diphenylamine are formed (B. 25, 992, 1013, 1019); thus ^-hydrazo-toluene, CH 3 C 6 H 4 NH NH C 6 H 4 - CH 3 , yields o-amino-di-^-toly lamine, CH 8 .C 6 H 4 .NH-C 6 H 8 <0|k (Cf. Jacobson, B. 1893, 26, 700; 1898, 31, 890; A. 1895, 28 3 7, 98.) Hydrazo-benzene, sym.-Diphenyl-hydrazine, C 6 H 5 NHe * : I 1 CgH 5 (Hofmann), forms colourless plates of camphor- like odour, which are only slightly soluble in water, but dissolve readily in alcohol and ether; m.-pt. 131. The imino-hydrogen atoms are replaceable by acetyl- or nitroso-groups. 3. AZO-COMPOUNDS The azo-compounds are red or yellowish -red, crystalline, neutral substances, insoluble in water, but soluble in alcohol; some of them may be distilled without change. Azo-benzene itself (benzene-azo-benzene, C 6 H 5 N:NC 6 H 5 ) crystallizes in large red plates, melts at 68, and distils at 293. Oxidizing agents convert them into azoxy-, and reducing agents into hydrazo- or amino-compounds. Chlorine and bromine act as substituents. The so-called "mixed" azo-compounds, which contain both ft PHENYL-HYDROXYLAMINE 397 an alphyl and an aryl radical, are also known, e.g. azo-phenyl- ethyl, C 6 H 5 .N:N.C 2 H 5 , a bright-yellow oil (B. 1897, 30, 793). Modes of Formation. 1. By the cautious reduction of nitro- or azoxy-compounds, e.g. by means of sodium amalgam or of an alkaline solution of stannous oxide (B. 18, 2912). 2. By distilling azoxy-benzene with iron filings. 3. By the oxidation of hydrazo-benzene. 4. By the oxidation of amino-compounds, e.g. together with azoxy-compounds by means of KMnO 4 : 2C 6 H 6 .NH 2 + 20 5. By the action of nitroso- upon amino-compounds in pre- sence of acetic acid. In this way azo-benzene is obtained from nitroso-benzene and aniline acetate : C 6 H 5 .NO + NH 2 .C 6 H 5 = C 6 H 5 .N:N-C 6 H 5 + H 2 0. Ammo- and hydroxy-derivatives of azo-benzenes are known, thus : C 6 H 6 .N:N.C 6 H 4 .NH 2 C 6 H 6 .N:N.C 6 H 4 .QH Amino-azo-benzene Hydroxy-azo-benzene. The former are at the same time bases and azo-compounds, and the latter azo-compounds and phenols (i.e. weak acids). (Cf. Azo-dyes, p. 399.) /2-Phenyl-hydroxylamine, C 6 H 5 .NH-OH, is formed when nitro-benzene is reduced with zinc dust and water, more especially in the presence of a mineral salt, e.g. CaCl 2 . It is a colourless crystalline substance melting at 81, and is rela f ' ly^unstable. Aqueous solutions rapidly undergo oxi- dation on exposure to the air, yielding azoxy-benzene; oxidiz- ing agents generally yield nitroso-benzene. Mineral acids immediately cause molecular rearrangement into p-amino- phenol, NH 2 -C 6 H 4 .OH (cf. p. 394). All the arylated /3-hy- droxylamines corresponding with phenyl-hydroxylamine reduce Fehling's solution, and this affords a test for an aromatic nitro- compound. If, after warming with water and zinc dust, a solu- tion is obtained which reduces FeMing's solution, the presence of a nitro-group in the original compound can be inferred. D. Hydrazines The aromatic hydrazines (E. Fischer) entirely correspond with those of the fatty series (cf. p. 111). Phenyl-hydrazine, C G H 5 NH NH 2 , s-diphenyl-hydrazine or hydrazo-benzene, C 6 H 6 NH NH C e H 6 ; unsym.-diphenyl- 398 XXII. DIAZO- AND AZO-COMPOUNDS hydrazine, (C 6 H 5 ) 2 N NEL and phenylmethyl - hydrazine, (C 6 H 5 )(CH 3 )N.NH 2 , are all known. Phenyl-hydrazine, C 6 H 5 NHNH 2 , forms a colourless crys- talline mass, melting at 23 to a colourless oil, which quickly becomes brown from oxidation, and which is best distilled under reduced pressure. When kept or when heated it under- goes slow decomposition (Chattaway). It forms salts with mineral acids, e.g. the hydrochloride, C 6 H 5 N 2 H 3 , HC1 (plates). Like all hydrazines, it has strong reducing power, reducing Fehling's solution even in the cold. It is readily destroyed by oxidation (Chattaway, C. N. 1911, 103, 217), but is stable to- wards mild reducing agents. Energetic reducing agents con- vert it into aniline and ammonia. Gentle oxidation of the sulphate by means of HgO converts it into benzene-diazonium sulphate. It is prepared: (a) by reducing benzene-diazonium chloride with the calculated quantity of SnCl 2 and HC1: C 6 H 6 N 2 C1 + 4H = C 6 H 6 .NH.NH 2 ,HC1; (b) by reducing potassium diazo- benzene -sulphonate, C 6 H 5 - NrN-SOgK (from 6 H 5 N 2 C1 and K 2 SO ? ), with zinc dust and icetic acid to potassium phenyl-hydrazine-sulphonate, C G H 5 NHNHS0 3 K, which is then hydrolysed to phenyl-hydrazine and sulphuric acid : CcH 5 .NH-NH.S0 8 K + HC1 + H 2 = CeHj-NH-NHa, HC1 + KHS0 4 . Alkyl and acyl derivatives of phenyl-hydrazine are known; the former (mono-alky lated derivatives only) are obtained by the action of alkyl iodides on the base or its metallic deriva- tives. Phenyl-methyl-hydrazine, which can be obtained in this way, is largely used for differentiating ketoses and aldoses (p. 302); its constitution follows from its formation by the /~1 TT reduction of nitroso-methyl-aniline, Q|J 6 ^>NNO. Both mono- and diacyl derivatives are known. The mono-acyl derivatives or hydrazides (cf. Amides, Anilides) are obtained by the action of the acid or acid anhydrides on the base; they give a violet-red coloration with sulphuric acid and dichromate of potash, and can be used for isolating acids which are readily soluble (B. 22, 2728), e.g. acetylphenyl-hydrazide, C 6 H 5 -NH. NH.CO-CH 8 ; m.-pt. 128. The base is an important and often an exceedingly delicate reagent for aldehydes and ketones, combining with them to hydrazones, with elimination of water (cf. pp. 127 and 135). AZO-DYE8 399 Most of these compounds are solid and crystalline, and are therefore eminently suited for the recognition of aldehydes and ketones. With certain sugars it yields phenyl-hydrazones, but with an excess of the base, osazones (p. 301) are formed. Diketones, keto-aldehydes, &c., also yield osazones. With ethyl aceto- acetate, phenyl-hydrazine forms pyrazole derivatives, &#. phenyl-methyl-pyrazolone, the methyl deriva- tive*of whrch is antipyrine (see p. 230). Drphenyl-hydrazine, (CgH 5 ) 2 NNH 2 , is an oily base which boils without decomposition, and, like phenyl-hydrazine, is easily oxidized; it only reduces Fehling's solution, however, when warmed. It is obtained by reducing diphenyl-nitros- amine, (C 6 H 5 ) 2 N-NO, with zinc dust and acetic acid. M.-pt. 34. Like phenyl-hydrazine, it yields characteristic hydra- zones and osazones with the sugars. ^-Bromo-phenyl-hydrazone, C 6 H 4 Br*NHNH 2 , and|?-nitro- phenyl-hydrazine are often used in isolating ketones, &c., as the phenyl-hydrazones thus obtained crystallize well (B. 1899, 32, 1806). E. Azo-dyes A number of compounds derived from azo-benzene and its homologues are largely used as dyes, under the name of azo- dyes. These compounds are either basic and contain NH 2 or N(CH 3 ) 2 groups, or are acidic and then contain either phenolic, OH, or sulphonic, S0 2 OH, and phenolic groups. Azo-benzene itself is a highly-coloured substance, but is not a dye. In order that a coloured substance shall be a dye, it is essential that the colour it imparts to a fabric shall not be removed by washing or treatment with soap. According to 0. Witi> when certain characteristic groups known as chromophores, among which are N:N and N0 2 , are present, the compound is coloured or is a chromogene ; and when, in addition to the chromophore, a strongly basic (e.g. NH 2 ) or acidic group (e.g. OH or S0 2 OH) is also present, we obtain a dye, e.g. : Chromogeues. Dyes. Nitre-benzene Nitraniline, N0 2 < C 6 H 4 -NH 2 ; Nitro-benzene Picric acid, (NO 2 ) 3 .C 6 H 2 .OH; ^.zo-benzene >-Hydroxy-azo-benzene, C 6 H 6 -N:N-C 6 H 4 'OH. The majority of dyes, when reduced, yield colourless com- pounds leuco-compounds which on oxidation are converted into the original dyes. With regard to the theory of the process of dyeing fabrics, 400 XXII. DIAZO- AND AZO-COMPOUNDS there are still two distinct schools. According to one, the process consists in the formation of definite compounds of the basic or acidic dye with acidic or basic constituents of the fabric dyed. According to the other, the operation is largely a physical one, and the dyed fabric may be regarded as a solid solution. In most cases, silk and woollen and in a few cases cotton fabrics can be dyed by direct immersion in a solution of the dye; but, as a jule, cotton will not dye directly, but recmires previous treatment with a mordant. The object of fehPmor- dant is to deposit some substance on the fabric which will afterwards combine with or fix the dye. The chief mordants employed for acid dyes are the feeble bases aluminic, chromic, or ferric hydroxides, obtained by immersing the fabric in a solution of the metallic acetate, and then subjecting to the action of steam. The product formed by the action of the dye on the mordant is known as a lake, and the same dye can give rise to different-coloured lakes, according to the mordant used. When basic dyes are employed for cotton goods, the fabric is usually mordanted with tannic acid. Stannic hy- droxide obtained from such a salt as SnCl 4 , 2NH 4 C1 is also used as a mordant. ^-Amino-azo-benzene is the parent substance of the dyes known as chrysoidines. It may be obtained (1) by nitrating azo-benzene and then reducing (this indicates its constitution as an amino-derivative of azo-benzene); (2) by molecular re- arrangement of diazo-amino-benzene (p. 393): ; gives NH 2 .C 6 H 4 .N:N.C 6 H 5 , another example of the wandering of a radical from a side chain into the benzene nucleus. The amino-group occupies the ^-position with respect to the azo-group. Substituted amino-azo-benzenes, e.g. dimethyl-amino-azo- benzene, are obtained directly by the action of a diazonium salt on a tertiary amine: = C 6 H 5 .N:N.C 6 H 4 .N(CH 3 ) 2 + HC1. Assuming the Blomstrand formula for the diazonium sait, the reaction is probably first additive, and then HC1 is eliminated : CHRYSOIDINES AND TROP^OLINES 401 The azo-group always takes up the ^-position with respect to the substituted amino-group if this position is free. If, however, the jo-position is already substituted, a dye is not formed, or is formed very incompletely, and the o-position is taken up. The chrysoidines are coloured yellow to brown, and, as they contain amino- or substituted amino-groups in the molecule, are basic, and form well-defined salts with mineral acids. Among the simplest chrysoidines we have : Aniline yellow, the hydrochloride of j;-amino-azo-benzene. It is now very little used. Chrysoidine, or 2-A-diamino-azobenzene hydrochloride, C r H 5 N : N . C 6 H 3 (NH 2 ) 2 , HC1 [N 2 : (NH 2 ) 2 = 1:2:4]. It dyes silk and wool directly an orange-red colour. Bismarck brown, or 3':Z'A-triamino-azo-benzene hydrochloride, NH 2 .C 6 H 4 .N:N.C 6 H 3 (NH 2 ) 2 ,HC1, is obtained by diazotizing w-phenylenediamine and coupling the diazonium salt with a second molecule of the base. The brown coloration obtained by the addition of a few drops of dilute nitrous acid solution to m-phenylenediamine is due to the formation of Bismarck brown or a related sub- stance. The hydrochloride crystallizes in reddish - brown plates. Many of the chrysoidine dyes are sulphonated derivatives of amino-azo-benzene. As an example, we have methyl orange, which is the sodium salt of helianthine or jp-dimethamino-azo- benzene-^-sulphonic acid, (CH 3 ) 2 N.C 6 H 4 .N:N.C 6 H 4 .S0 2 .OH. It is largely made use of as an indicator in volumetric analysis, as it is not affected by weak acids, e.g. carbonic, but is an ex- tremely delicate reagent for the feeblest alkalis. The dyes known as tropaeolines are derivatives of ^-hydroxy- azo-benzene. Such compounds are obtained by adding the cold diazotized solution to an alkaline solution of a phenol. The dye is then salted out by the addition of sodium chloride and collected. The reaction is often made use of in testing for a primary aromatic amine (p. 389), as the precipitates produced are usually coloured bright red. The azo-group invariably occupies the p-position with respect to the OH group, unless this is already substituted. ^-Hydroxy-azo-benzene crystallizes in brick-red prisms, and is a yellowish-red dye. Resorcin yellow, OH.S0 2 .C 6 H 4 .N:N ; C 6 H 3 (OH) 2 , 2A-di- hydroxy-azo -benzene- 4' '-sulphonic acid, obtained by coupling a (B480) 2C 402 XXII. DIAZO- AND AZO-COMPOUNDS diazotized solution of sulphanilic acid with an alkaline solu- tion of resorcinol, is known as Tropseolin 0. The constitution of an azo-dye can usually be determined by an examination of its decomposition products, especially the products formed by energetic reduction ; e.g. Bismarck brown, on reduction with tin and hydrochloric acid, yields a mixture of 1 : 3-diamino- and 1:2: 4-triamino-benzene : NH 2 : NH, <( \N:|N N / 2H ; 2I_ Bis-azo-dyes. Certain well-known dyes, e.g. Biebrich scarlet, contain two azo-groups. Such can be obtained by diazotizing an amino-derivative of azo-benzene, and then coupling it with a tertiary amine or with a phenol, and we thus obtain com- pounds of the type C g H 5 .N:N.C 6 H 4 .N:N.C 6 H 4 .OH. Another type of bis-azo-compound is formed by coupling a diamine or dihydric phenol with 2 mols. of a diazonium salt. Many amino- and hydroxy-azo-derivatives react as tauto- meric substances, especially those which contain an NH 2 01 OH group in the ortho - position with respect to the N 2 radical. These react as though they were quinone hydra- zones or quinone-imide derivatives, e.g.: C 6 H 5 .N:N.C 6 H 4 .OH C 6 H 6 NH.N:C 6 H 4 :O, C 6 H 6 .N:N.C 6 H 4 .NH 2 C 6 H 6 .NH.N:C 6 H 4 :NH. For a general summary compare Auwers (A. 1908, 360, 11). The general conclusion drawn is that all the compounds, both para and ortho, are true hydroxy-azo-compounds. According to Hantzsch, many of the hydroxy-azo-compounds are pseudo-acids (p. 363), i.e. the hydrogen compound is the quinone hydrazone; but in the formation of a salt, intra- molecular rearrangement occurs, and the salt thus has a con- stitution quite different from that of the parent substance, e.g.: C 6 H 5 .NH.N:C 6 H 4 :0 - F. Phosphorus Compounds, &c.; Org-ano-Metallie Derivatives The phosphorus, &c., compounds of the fatty series have their analogues in corresponding compounds of the aromatic; these latter have been investigated by Michaelis and his pupils (A. 181, 188, 201, 212, and 229 ; B. 28, 2205): for SULPHONIC ACIDS 403 instance, phenyl phosphine, C G H r .PH 2 ; phenyl phosphinic acid, C 6 H 5 PO(OH) 2 ; phosphenyl chloride, C tf H 5 -PCl 2 ; phos- phino-benzene, C 6 H 5 P0 2 ; and phospho -benzene, C 6 H 5 P:P C 6 H 5 (these two last being analogous to nitro- and to azo- benzene). Some of those compounds are solid, and they are less volatile and more stable than the corresponding aliphatic compounds. Corresponding derivatives of arsenic are also known. Aromatic Organo - Metallic Compounds. Mercury, tin, lead, tellurium, and magnesium yield phenyl derivatives. Mercury phenyl, Hg(C 6 H 5 ) 2 , is obtained by the action of sodium amalgam of bromobenzene. It is relatively stable. Numerous compounds of the type of phenyl magnesium bromide, C 6 H 5 -Mg-Br, have been prepared, and are used as synthetical reagents (cf. p. 356). XXIII. ABOMATIC SULPHONIC ACIDS The aromatic sulphonic acids are very similar in properties to the sulphonic acids of the fatty series, but can be obtained much mofe readily. One of the characteristic properties of benzene and its derivatives is the readiness with which they react with concentrated sulphuric acid, yielding sulphonic acids. In some cases fuming sulphuric acid is used; in others sulphuryl chloride, OH-SO^Cl. Benzene-sulphonic acid, C 6 H 5 .S0 2 OH (Mitscherlich, 1834), is formed when benzene is heated with concentrated sulphuric acid for some hours : C 6 H 6 + S0 2 (OH) 2 = C 6 H 5 .S0 2 .OH + H 2 0. As in the case of ethyl hydrogen sulphate, advantage is taken of the solubility of its barium, calcium, or lead salt to separate it from the excess of sulphuric acid; or its sodium salt is separated by the addition of sodium chloride. It crystallizes in small plates containing 1JH 2 0, deliquesces in the air, and is readily soluble in alcohol. The barium salt crystallizes in glistening mother-of-pearl plates containing 1H 2 O. It is very stable, and is not hydrolysed when boiled with alkalis or acids (cf. Ethyl hydrogen sulphate). It is, however, 404 XXIII. AROMATIC SULPHONIC ACIDS decomposed into benzene and sulphuric acid when heated with hydrochloric acid at 150, or with water vapour at a high temperature (cf. p. 347): C 6 H 5 .S0 2 .OH + H 2 = C 6 H 6 + S0 2 (OH) 2 . When fused with alkali, it yields phenol in the form of its potassium salt: C 6 H 5 .S0 3 K + 2KOH =- C 6 H fi .OK + S0 3 K 2 + H 2 0, and when distilled with potassium cyanide, it yields benzo- nitrile: C 6 H 6 .SO 3 K + CNK = C 6 H 6 .CN + S0 3 K 2 . With PC1 5 the OH group present in the sulphonic acid radical is replaced by chlorine, and benzene-sulphonic chloride is formed: C 6 H 6 .S0 2 OH-f PC1 6 = C 6 H 5 -S0 2 C1-|-POC1 3 + HC1. This is an oil, insoluble in water; it melts at 14-5, and boils at 120 (under 10 mm. pressure); as an acid chloride it is reconverted into sulphonic acid by hot water, into the corre- sponding esters by alcohols, and into benzene-sulphonamide, C 6 ELS0 2 NH 2 (lustrous mother-of-pearl plates melting at 150), by ammonia. This compound can be sublimed, and corresponds with other amides in its properties. The amido- group, however, is so affected by the strongly acidifying action of the S0 2 group that its hydrogen is replaceable by metals, and the sulphonamides consequently dissolve in aqueous solutions of alkali hydroxides. The sulphonamides are largely made use of in distinguish- ing the various sulphonic acids. These acids themselves are difficult to purify, as a rule do not crystallize well, and have no definite melting-point. The sulphonamides, on the other hand, crystallize readily, and have sharp melting-points. The sodium salt of the acid is treated with PC1 5 , and the chloride thus obtained is warmed with ammonium carbonate. Benzene-sulphonic chloride likewise yields sulphonamides with primary and secondary amines, C 6 H 5 'S0 2 NHR and C 6 H 5 'S0 2 NRB/, the former of these being soluble in alkali, but the latter insoluble. Tertiary amines do not, of course, give sulphonamides. This serves as the basis of a method for separating primary, secondary, and tertiary bases, especially AMINO-SULPHONIC ACIDS 405 when /3-anthraquinone sulphonic chloride is used (Hinsberg, B. 23, 2962; 1900, 33, 477, 557, 3526; 38, 906). When benzene-sulphonic chloride is treated with zinc dust, zinc benzenesulphinate is formed : 2C 6 H 6 .S0 2 Cl + 2Zn = (C 6 H 6 S0 2 ) 2 Zn + ZnCl 2 . An alkaline sulphinate is also produced (along with phenyl disulphide as by-product) when benzene-sulphonic chloride is treated with thio-phenol in presence of alkali. Benzene-sulphuric acid crystallizes in large glistening prisms, readily soluble in hot water, alcohol, and ether. It possesses reducing properties, and is itself converted into thio-phenol by nascent hydrogen: C 6 H 6 .S0 2 H + 4H = C 6 H 6 SH -f 2H 2 0. Substitution may be effected in benzene-sulphonic aoid by chlorine, bromine, and the groups N0 2 and NH 2 . The nitro-benzene-sulphonic acids, N0 2 C 6 H 4 S0 3 H, are obtained by nitrating benzene-sulphonic acid or by sulphonat- ing nitro-benzene, the w-compound preponderating. Reduc- ing agents convert them into the Amino- benzene -sulphonic acids, NH 2 'C 6 H 4 S0 3 H. The ^-compound, which is termed sulphanilic acid, is obtained by heating aniline sulphate at 180-200 (Gerhardt, 1845); also by reducing ^-nitro-benzene-sulphonic acid. The conversion of aniline sulphate into sulphanilic acid proceeds in the following stages : NH 3 HSO 4 NH.SO 2 -OH Aniline hydrogen Phenylsulphonamto sulphate acid SO 2 'OH Aniline Sulphanilic acid o-siilphonic acid. (Of. Eamberger, B. 1897, 30, 2274.) It crystallizes in rhombic plates (+ H 2 O), sparingly soluble in water, forms metallic salts, 406 XXIII. AROMATIC SULPHONIC ACIDS e.g. sodium sulphanilate, NH 2 C 6 H 4 S0 8 Na + 2H 2 (large plates), but does not combine with acids. The formula C 6 H 4 <^qQ 3 /> possibly expresses the constitution of sulph- anilic acid. The m-acid, also termed metanilic acid, is em- ployed in the preparation of azo-dyes, e.g. metaniline yellow; it crystallizes in fine needles or prisms. Diazo-benzene-sulphonic acid, C 6 H 4 <^gQ ^> (the anhydride of C 6 H 4 <^Q TT Y is obtained by adding a mixture of sul- phanilate and nitrite of sodium to dilute sulphuric acid. It forms colourless needles, sparingly soluble in water, shows all the reactions of the diazo-compounds, and is of great impor- tance for the preparation of azo-dyes. Benzene-disulphonic acids, C 6 H 4 (S0 3 H) 2 (principally meta-), and benzene-trisulphonic acids, C 6 H 3 (S0 3 H) 3 , result from the energetic sulphonation of benzene with fuming sulphuric acid. The former exist, of course, in three isomeric modifications. "When they are distilled with KCN, they yield the compounds C 6 H 4 (CN) 2 , the nitriles of the phthalic acids; when fused with KOH, the m-disulphonic acid changes into resorcinol (m-di- hydroxy-benzene), G 6 H 4 (OH) 2 . Almost all the homologues of benzene, with the exception of hexamethyl-benzene, yield sulphonic acids. From toluene are obtained the o-, m-, and ^-toluene sulphonic acids, CH 3 - C 6 H 4 .S0 3 H (Hollemann and Caland, B. 1911, 44, 2504). Of these it is the p-acid which is formed in largest quantity directly; its potassium salt crystallizes beautifully. The sulphonic acids of the three xylenes, the xylene-sul- phonic acids, C 6 H 3 (CH 3 \ 2 S0 3 H, serve for the separation of these isomers from each other; and the power of crystalliza- tion of the salts or amides of the sulphonic acids of the higher benzene homologues is frequently made use of for the recog- nition and separation of these hydrocarbons. The above instances are sufficient to show that sulphonic acids may be obtained from the most complicated aromatic compounds. This is of especial importance if the latter are dyes whose application is hindered by their insolubility in water, as in the case, e.g., of indigo, amino-azo-benzene, &c. The sulphonated dyes, however, are usually inferior to their originals in colouring power arid purity, e.g., they do not stand the effects of light so well. XXIV. PHENOLS 407 XXIV. PHENOLS The hydroxylic derivatives of benzene and its homologues are usually divided into (a) phenols and (b) aromatic alco- hols. The phenols all contain the hydroxyl group or groups directly attached to the benzene nucleus, e.g. C 6 H 5 (OH), C 6 H 4 (OH) 2 , whereas in the alcohols the hydroxyl group is present in a side chain, e.g. C 6 H 5 CH 2 -OH. One important point of difference between the phenols and alcohols is the more pronouncedly acidic nature of the phenol. The aromatic alcohols closely resemble those of the aliphatic series, but the phenols react as feeble acids, the hydroxylic hydrogen being displaced by the action of sodium or potassium hydroxide. The phenols are either liquid or solid compounds, and are often characterized by a peculiar odour, e.g. carbolic acid and thymol. Most of them can be distilled without decomposition, and all are readily soluble in alcohol or ether; some dissolve easily in water, others less readily, the solubility tending to increase with the number of hydroxyl groups present in the molecule. Many of them are antiseptics, e.g. phenol, creosol, and resorcinol. . The phenols are usually divided into mono-, di-, tri- or tetra- hydric, according to the number of OH groups present in the molecule. Behaviour. 1. Like the alcohols, the phenols are capable of forming ethers such as anisole, C 6 H 5 0-CH 3 , esters, e.g. phenyl acetate, C 6 H 5 CO CH 3 , and phenyl hydrogen sulphate, C 6 H 6 S0 2 OH, thio-coinpounds, e.g. thiophenol, C 6 H 5 .SH, &c. They can only be compared with the tertiary alcohols, since they cannot, like the primary or secondary alcohols, yield acids or ketones containing an equal number of carbon atoms in the molecule upon oxidation. 2. The phenols are weak acids, and form salts known as phenates or phenoxides, e.g. C 6 H 5 OK, potassium phenate or potassium phenoxide; most of the salts are readily soluble in water, and far more stable than the alcoholates, with which they correspond. In aqueous solutions the salts are largely hydrolysed, and are decomposed by carbon dioxide, as the phenols are ex- tremely feeble acids comparable with hydrocyanic acid (cf. Walker, Phys. Chem., chapter xxiv). The acid character of the 408 XXIV. PHENOLS J^O) CD Ci 66 o o o o o CO (N Oi ^ l>- i i CM O CO CO CM (N <?q CM <M o I-H o 2 cq o cq co -^ I CM W S 1 REACTIONS OF PHENOLS 409 phenols is considerably increased by the entrance of negative groups, especially N0 2 , into the molecule. (See Picric acid; also Abst. 1903, 1, 754.) 3. The presence of NH 2 or OH groups in the benzene nucleus renders compounds much more reactive towards halo- gens, nitric acid, sulphuric acid, oxidizing agents, &c. With polyamines and aminophenols the reactivity is such that the compounds undergo spontaneous oxidation on exposure to the air. The reactivity with chlorine is so great that frequently compounds of this type cannot be chlorinated by the usual methods. Orton and King (J. C. S. 1911, 1185) have introduced a method based upon the fact that the reversible reaction: K-NClAc + HCl ^ B-NHAc proceeds from left to right in the presence of glacial acetic acid, and thus by taking very dilute solutions of hydrochloric acid, e.g. 0*021 N, the concentration of the chlorine is kept so low that chloro-derivatives are obtained free from products of oxidation. Cresols can be chlorinated in the same manner. The acetyl derivative generally used is 2 : 4-dichloro-acetyl- chloranilide, and if the theoretical amount of this compound is used the reaction proceeds to completion, as hydrogen chloride is formed by the action of the chlorine on the amine or phenol. 4. Many phenols give characteristic colorations with ferric chloride in neutral solution, e.g. phenol and resorcinol violet, catechol green, and orcinol blue-violet; while pyrogallol yields a blue colour with ferrous sulphate containing a ferric salt, and a red one with ferric chloride. Bleaching-powder and iodine solution, in certain cases, also give particular coloration. 5. Liebermann's Reaction. When the phenols are mixed with concentrated H 2 S0 4 and a drop of nitrite solution or of a nitrosamine, they yield intensely coloured solutions which turn to a deep-blue or green when diluted and rendered alkaline with potash. 6. The sodium and potassium salts of the phenols react with C0 2 (Kolbe) or with COC1 2 , with formation of aromatic hydroxy-acids, e.g. salicylic acid (see this). For further methods of preparation of hydroxy-acids and aldehydes, see Tiemann-Reimer reaction (pp. 430 and 440). 7. The phenols couple with diazonium salts to form azo- dyes (p. 389); when heated with benzo-trichloride, CgHyCC^, they yield yellow-red dyes (see Aurin), and with phthalic acid, the phthaleins (see Phenol-phthalein). 410 XXIV. PHENOLS 8. When heated with zinc dust, the phenols are converted into the corresponding hydrocarbons (Baeyer). 9. When heated with the additive compounds of zinc chloride and ammonia or calcic chloride and ammonia, the OH is replaced by NH 2 (cf. p. 368; also B. 19, 2901). 10. Heating with phosphorus pentachloride partially con- verts the phenols into chlorinated hydrocarbons, and heating with P 2 S 5 into thio-phenols. Occurrence. Many individual phenols are found in the vegetable and animal kingdoms, and also in coal-tar. Constitution. The hydroxyl-groups in phenol, C 6 H 5 OH, and in the di- and polyhydroxy-benzenes, containing six carbon atoms, are linked to the benzene nucleus. That this is also the case in the homologues of these compounds follows: (a) from their completely analogous reactions; (b) from their behaviour upon oxidation. Thus, when oxidized, w-cresol yields m-hydroxy-benzoic acid, and hence the OH is present in the benzene nucleus and not in the side chain, and must be in the m-position with respect to the methyl group. A. Monohydrie Phenols Modes of Formation. 1. Many phenols are formed during the destructive distillation of the more complex carbon com- pounds, especially of wood and coal; they are therefore present in wood- and coal-tars. The latter contains more especially phenol and its homologues, cresol, &c.; the former, among other products, the methyl ethers of polyhydric phenols, e.g. guaiacol, C 6 H 4 (OH)(0CH 3 ), and its homologue creosol, C 6 H 3 (CH 3 )(OH)(O.CH 3 ). The phenols are isolated from coal-tar, &c., by shaking with sodic hydroxide solution, in which they dissolve, saturating the alkaline solution with hydrochloric acid, and purifying the precipitated phenols by fractional distillation. 2. Phenols are formed together with an alkali sulphite when salts of sulphonic acids are fused with potassic or sodic hy- droxides (KekuU, Wurtz, Dusart, 1867): C 6 H 6 .S0 3 K + 2KOH = C 6 H 6 .QK + SO 3 K 2 + H 2 O. In the laboratory nickel or silver basins are used for this fusion, and on the large scale iron boilers, c. The alkali salts of the phenols are formed, and the free phenols may be liberated, by the addition of mineral acid. The chlorinated PREPARATION OF PHENOLS 411 sulphonic acids and the chlorinated phenols also exchange the halogen for hydroxyl when fused with potash: C 6 H 4 C1(SO 3 K) -f 4KOH = C 6 H 4 (OK) 2 + SO 3 K 2 -f KC1 + 2H 2 0. In certain cases intramolecular rearrangement occurs during this fusion, e.g. all three bromo-benzene-sulphonic acids, the ortho-, meta-, and para-, yield m-dihydroxy-benzene (resorcinol) when fused with potash. 3. They are formed when aqueous solutions of diazonium salts are heated (Griess-, cf. p. 387). As a rule, a very dilute sulphuric acid solution is employed: C 6 H 4 C1(N 2 C1) -f- H 2 O = C c H 4 Cl-OH + N 2 -f HC1. 4. Phenol is produced from benzene by the action of ozone or hydrogen peroxide, and also by that of the oxygen of the air in presence of caustic soda solution or of aluminium chloride. In an analogous manner di- and even trihydroxy- benzene may be obtained by fusing phenol with potash : C C H 6 .OH + = C 6 H 4 (OH) 2 . 5. The phenols cannot be prepared from chloro-, bromo-, or iodo-benzene in the same way as the alcohols from alkyl chlorides, bromides, or iodides, the halogen being bound too firmly to the benzene nucleus. If, however, nitro-groups are present in o- or ^-positions, an exchange of this kind can be effected by heating with aqueous sodium or potassium hy- droxides; trinitro-chloro-benzene indeed reacts with water alone : C C H 2 C1(N0 2 ) 3 + HOH = C 6 H 2 (OH)(N0 2 ) 3 + HC1. Similarly, the amino-group in amino-compounds may be replaced by hydroxyl by means of boiling alkalis, provided nitro-groups are also present in certain position; thus o- and p- (not m-) dinitro-aniline yield dinitro-phenols, a reaction which corresponds with the saponification of the amides (cf. pp. 362 and 374). 6. Phenols are also formed when salts of the aromatic hydroxy-acids are distilled with lime, or when their silver salts are carefully heated: C C H 2 (OH) 3 .C0 2 H = C0 2 -hC G H 3 (OH) 3 Gallic acid Pyrogallol. Phenol, Carbolic acid, hydroxy -benzene, C 6 H 5 OH, was dis- 412 XXIV. PHENOLS covered in 1834 by Runge in coal-tar. It occurs in the urine of the herbivora and in human urine as phenyl hydrogen sul- phate, also in castoreum, and in bone-oil. It forms a colourless crystalline mass consisting of long needles, melts at 42, boils at 181, is soluble in fifteen parts of water at 16, and itself dissolves some water, a small percentage of the latter sufficing to liquefy the crystalline phenol. Alcohol and ether dissolve it readily. It is hygroscopic, and acquires a reddish colour in the air owing to the presence of impurities, possesses a character- istic odour and burning taste, is poisonous, acts as a splendid antiseptic, and exerts a strongly corrosive action upon the skin. As a very feeble acid it dissolves readily in caustic potash solution, but not in the carbonate. Ferric chloride colours the aqueous solution violet, while a pine shaving moistened with hydrochloric acid is turned greenish-blue by phenol. Hexahydro-phenol, 6 H U OH, prepared from quinitol (cyclo- hexane-1 : 4-diol) (B. 26, 229), is a liquid with an odour resem- bling that of fusel oil. Anisole, or Phenyl methyl ether, C 6 H 5 CHg, and phenetole, or phenyl ethyl ether, C 6 H 5 C 2 H 6 , are best obtained by heat- ing phenol and caustic potash with methyl or ethyl iodide in alcoholic solution : C 6 H 5 .OK + CH 3 I = C 6 H 5 .OCH 3 -}-KIj the former is also obtained by distilling anisic acid with lime. They are liquids of ethereal odour which boil at a lower temperature than phenol, just as ether has a lower boiling- point than alcohol. They are very stable neutral compounds, which are not readily hydrolysed by acids or alkalis; when heated with HI to 140, or with HC1 to a higher temperature, or with aluminium chloride, they are decomposed, yielding phenol : Phenyl ether, Diphenyl oxide, (C 6 H 5 ) 2 0, is formed when phenol is heated with ZnCl 2 or AlClg, but not with H 2 S0 4 . It crystallizes in needles, and is not decomposed by hydriodic acid. Esters. Phenyl hydrogen sulphate, C 6 H. S0 2 OH (cf. Ethyl hydrogen sulphate), is only capable of existence in the form of salts, being immediately hydrolysed into phenol and sulphuric acid when attempts are made to isolate it. The potassium salt, C 6 H 6 0S0 2 .OK (plates, sparingly soluble in THIO-PHENOL 413 water), is found in the urine of the herbivora and also in human urine after the consumption of phenol, and it may be prepared synthetically by heating potassium phenate with potassic pyro-sulphate in aqueous solution (Baumann). It is very stable towards alkalis, but is saponified by hydrochloric acid. Phenyl acetate, C,HLO CO CH 3 , obtained from phenol, acetic anhydride, and dry sodic acetate, is a liquid which boils at 193, and is readily hydrolysed (cf. Ethyl acetate). Thio-phenol, Phenyl hydrosulphide, C 6 H 5 SH, is prepared from benzene-sulphonic chloride, C 6 H 5 'S0 2 C1, as given at p. 405, or by heating phenol with P 2 S 5 . It is a liquid of most unpleasant odour and of pronounced mercaptan char- acter (see p. 89). It yields, for instance, a mercury com- pound, (C 6 H 6 S) 2 Hg, crystallizing in glistening needles, and also salts with other metals. When warmed with concen- trated H 2 S0 4 , a cherry-red and then a blue coloration is produced. Closely related to the above are: (a) phenyl sulphide, (C 6 H 5 ) 2 S, which is formed by the action of benzene-diazonium chloride upon thio-phenol (B. 23, 2469): It is a liquid smelling of leeks, and is oxidizable to phenyl sulphone, (C 6 H 5 ) 2 S0 2 ; (b) phenyl disulphide, (C 6 H 5 ) 2 S 2 (glisten- ing needles, m.-pt. 60), which is very easily prepared by the action of iodine upon the potassium compound of thio-phenol, or by exposing an ammoniacal solution of the latter to the air. It is readily reduced to thio-phenol, and may be indirectly oxidized to benzene-disulphoxide, (C 6 H 5 ) 2 S 2 2 . (Cf. the cor- responding compounds of the fatty series, p. 89, et seq.) SUBSTITUTED PHENOLS Chloro- and Bromo-phenols. When chlorine is led into phenol, o- and j?-chloro-phenols are formed. These, and also the m-compound, may be obtained by reducing and diazotizing the haloid nitro-benzenes. Of the isomeric di-derivatives, the ^-compounds have the highest melting-point and the o- the lowest; thus 0-chloro- and bromo-phenols are liquid and the ^-compounds solid. When fused with caustic potash they yield dihydroxy - benzenes (p. 411), often with a molecular rearrangement. The chloro- 414 XXIV. PHENOLS phenols have a sharp, persistent odour. All the 5 hydrogen atoms of phenol can be replaced by chlorine and bromine. When an excess of bromine water is added to an aqueous solution f phenol, a precipitate of s-tribromo-phenol (colour- less needles, melting at 92) is obtained. Nitroso-phenol, OH'C 6 H 4 NO, prepared from phenol and nitrous acid (Baeyer, B. 7, 964), by boiling nitroso-dimethyl- aniline with caustic -soda solution (see p. 378), and by the action of hydroxylamine upon quinone, is identical with qui- none monoxime, 0:C 6 H 4 :NOH (p. 430). It crystallizes in fine colourless needles which readily become brown, or in large greenish-brown plates, and detonates when heated. Nitro-phenols. A mixture of o- and p-nitio -phenols is ob- tained when phenol is mixed with cold dilute nitric acid; the ^-compound preponderates if the liquid is cold, and the ortho- if it is warm. When distilled with steam, the 1:2 compound volatilizes, while the 1:4 remains behind. m-Nitro-phenol is obtained by diazotizing w-nitraniline. The o- and jp-compounds can also be obtained by fusing o- and ^-nitranilines with potash, and ^-nitro-phenol has been synthesised from nitro-malonaldehyde, NO 2 CH(CHO) 2 , and acetone (Hill and Torray, B. 1895, 28, 2598). The o-compound crystallizes in yellow prisms, and melts at 45, the m- in yellow crystals, melting at 96, and the para- in colourless needles, melting at 114. The acid character of phenol is so strengthened by the entrance of the nitro-group that its salts are not decomposed by carbonic acid, but are formed from the nitro-phenols and alkali carbonate. Sodium o-nitro-phenate, C 6 H 4 (N0 2 )ONa, crystallizes in dark -red prisms, and potassium jo-nitro-phenate in golden needles. (For constitution of the salts, see chapter on Absorption Spectra.) Halogens and nitric acid readily substitute further in these mono-nitro-compounds ; nitric acid yields two isomeric dinitro-phenols, C 6 H 3 (N0 2 ) 2 OH, (OH: NO 2 :N0 2 = 1:2:4 and 1:2:6, i.e. tt-e two N0 2 groups are always in the m-position to one another). Further nitration in the presence of sulphuric acid gives Picric acid, s-Trinitro-phenol, C 6 H 2 (N0 2 ) 3 .OH, (OH:N0 2 : N0 2 :N0 2 = 1:2:4:6). This compound was discovered in 1799. It may also be prepared by the direct oxidation of s-trinitro-benzene with K 3 FeC 6 Ng, and is produced by the action of concentrated nitric acid upon the most varied or- ganic substances, e.g. silk, leather, wool, resins, and aniline. AMINO-PHENOLS 415 It is a strong acid and forms beautifully crystalline salts, which explode violently when heated or struck. It crystallizes from alcohol or water in yellow plates or prisms, melting at 122, is only sparingly soluble in water, and the aqueous solutions have a persistent deep-yellow colour. It is used for the preparation of explosives, and is also a yellow dye. Picryl chloride, CLH ? (N0 2 ) 3 C1 (from picric acid and PC1 5 ), resembles the acid chlorides (p. 362) in behaviour. Picric acid forms beautifully crystallizing additive compounds with many aromatic hydrocarbons, and also with amines and phenols. Ammo-phenols are obtained by the reduction of nitro- phenols : C 6 H 4 (OH)NH 2 C 6 H s (OH)(NH 2 ) a C 6 H 3 (OH)(N0 2 )(NH 2 ) C 6 H 2 (OH)(NH a ) 8 0-, m-, p- Diamino- Nitro-amino- Triamino- Amino-phenols phenols phenols pheuoL In the amino-phenols (Hofmann, 1857) the acid character of the phenols is neutralized by the presence of the amino-group, so that they only yield salts with acids. The amino-phenols themselves are relatively unstable, and readily decompose on exposure to moist air or sunlight, but the hydrochlorides are much more stable. Derivatives of these compounds, as phenols and as amines, are known. The amino-hydrogen is readily replaceable by acyl groups. ^-Ammo-phenol, m.-pt. 184, obtained by the electrolysis of nitrobenzene in concentrated sulphuric acid (Gattermann), or by molecular rearrangement from /3-phenyl-hydroxylamine, is easily oxidized to quinone, C 6 H 4 2 , and is converted by bleaching-powder into quinone chlor-imide, O:C 6 H 4 :NC1. It is used as a photographic developer under the name of rodinal. Amidol is a salt of 2:4-diamino-phenol. m-Amino-phenol and diethyl-m- ammo-phenol, C 6 H 4 (OH) [N(C 2 H ) 2 ], are formed when m-amino-benzene-sulphonic acid or its diethyl-derivative is fused with alkali. The anisidines, amino-anisoles, methoxy-anilines, CH 3 0C 6 H 4 NH 2 , and the phenetidines, C 2 H 5 O.C 6 H 4 -NH 2 , are bases similar to aniline, and are used in the colour industry (azo- dyes). The acetyl derivative, aceto-p-phenetidine, C 2 H 5 C 6 H 4 NH'CO'CH 3 , which forms colourless crystals, is used as an anti-pyretic and as a remedy for neuralgia under the name of "Phenacetine". Phenocoll is lactyl-phenetidine. Numerous complex sulphur compounds derived from amino- phenols are used as dyes (e.g. Primulines, Vidal-black, &c.). 416 XXIV. PHENOLS Phenol-sulphonic acids, OH- C 6 H 4 -S(V OH. The o- and |?-acids are obtained from phenol and concentrated H S0 4 at a moderate temperature, that is, with much greater ease than the benzene-sulphonic acids; the ortho-acid changes into the para- when its aqueous solution is heated. The two acids may be separated by means of their potassium salts. The m-compound can be prepared indirectly by fusing m-benzene- disulphonic acid with potash. All three are crystalline. The o- and m-acids yield o- and wi-dihydroxy-benzenes when fused with KOH, but the ^?-acid does not react in this way, being attacked only at temperatures over 320, when complex products are formed. 0-Phenol-sulphonic acid is used as an antiseptic under the name of "Aseptol" or "Sozolic acid"; simi- larly, the salts of di-iodo-^-phenol-sulphonic acid, OHC 6 H 2 I 2 - S0 3 H, "Sozo-iodol", form antiseptics resembling iodoform. HOMOLOGUES OF PHENOL The homologues of phenol resemble the latter very closely in most of their properties, form perfectly analogous deriva- tives, possess disinfecting properties, and also a peculiar odour (the cresols an unpleasant faecal-like, and the higher homo- logues only a faint odour). They differ from phenol mainly by the presence of side chains which, as in the case of toluene, &c., may undergo certain transformations. Especially when they are used in the form of alkyl or acyl derivatives or acid sulphates, they can be oxidized in such a manner that the side chains (methyl groups) are transformed into carboxyl, with the production of hydroxy-carboxylic acids. The cresols themselves cannot be oxidized in this way even by chromic acid mixture, and are completely destroyed by potassic permanganate. Negative substituents, especially if they are present in the 0-position, render such oxidation more difficult in acid, but facilitate it in alkaline solution. All three cresols, CH 3 C 6 H 4 OH, are present in coal-tar, and are also contained in the tar from pine and beech wood; they are most readily prepared from the corresponding toluidines. 0-Cresyl hydrogen sulphate (analogous to phenyl hydrogen sulphate) is found in the urine of horses, and the ^-compound in human urine. m-Cresol is conveniently prepared by heating thymol with phosphoric anhydride and then with potash. DIHYDRIO PHENOLS 417 ^-Cresol is produced during the putrefaction of albumen. Its dinitro-compound is a golden-yellow dye which is used as ammonium or potassium salt under the name of Victoria orange. Crude cresol is rendered soluble in water by the addition of resin soap or of oil soap; the preparations so obtained are termed creoline and lysol, and are employed as antiseptics. Thymol, C^H^O, I -methyl- 4: -isopropyl- 3 -hydroxy -benzene, is found together with cymene, C 10 H 14 , and thymene, 10 Hj 6 , in oil of thyme, Thymus Serpyllum, and is used as an antiseptic. The isomeric carvacrol, l-methyl-^-isopropyl-Z-hydroxy-benzene, present in Origanum hirtum, is prepared either by heating camphor with iodine or from its isomer, carvol, and glacial phosphoric acid. The constitutions of these two phenols have been established as follows : (a) Both yield cymene (^-methyl-isopropyl-benzene) when heated with phosphorus sulphide and similar compounds. (b) Carvacrol, when heated with phosphorus pentoxide, yields propylene and o-cresol. (c) Thymol, when similarly treated, yields propylene and m-cresol. C 3 H 7 .C 6 H 3 (CH 3 )(OH) = C 3 H fl + OH.C 6 H 4 .CH 3 (oorm). B. Dihydrie Phenols By the entrance of two hydroxyls into benzene and its homologues, the dihydric phenols are produced. These are analogous to the monohydric compounds in most of their relations, but differ from them in the same way as the dihydric alcohols from the monohydric. The methods of formation are analogous to those used for the monohydric phenols, especially by fusion of sulphonic acids and halogen derivatives with potash; instead, however, of the compound expected, an isomeride which is stable at that high tempera- ture frequently results (see Resorcinol). The j?-dihydroxy- compounds are characterized by their close connection with the quinones. Many of the polyhydric phenols are strong reducing agents. Catechol, formerly called pyrocatechin, C 6 H 4 (OH) 2 (1:2), which was first obtained by the distillation of catechin (Mimosa Catechu), is present in raw beet-sugar, and is ob- tained when many resins or 0-phenol-sulphonic acid are fused with potash. It crystallizes in short, white, rhombic prisms, (B480) 2D 418 XXIV. PHENOLS which can be sublimed, and dissolves readily in water, alcohol, and ether. It is usually prepared by heating its mono-methyl ether, guaiacol, C 6 H 4 (OH)(OCH 3 ), a constituent of beech-wood tar, with hydriodic acid (see Anisole, p. 410). Like most of the polyhydric phenols, it is very unstable in alkaline solution, which quickly becomes green and then black in the air. The aqueous solution is coloured green by ferric chloride, and then violet by ammonia (reactions of the o-dihydroxy-com- pounds). It possesses reducing properties, and precipitates silver even from a cold solution of silver nitrate. By the con- tinued action of chlorine upon it, derivatives of pentamethy- lene and finally of the fatty series result (Zincke and Kuster). By boiling it with potash and potassic methyl-sulphate, it may be reconverted into guaiacol, which likewise shows the ferric chloride reaction and possesses reducing powers. Resorcinol, or m-Dihydroxy-benzene (Hlasiwetz, Barth, 1864), is obtained when many resins (Galbanum, Asafcetida), m-phenol- sulphonic acid, all three bromo-benzene-sulphonic acids, or m- and j?-benzene-disulphonic acids are fused with potash. The last- mentioned compounds are employed for its preparation on the technical scale. It crystallizes in rhombic prisms or plates, which quickly become brown in the air, dissolves readily in water, alcohol, and ether, and reduces an aqueous solution of silver nitrate when warmed with it, and an alkaline solution even in the cold. With ferric chloride it gives a dark-violet coloration. It acts therapeutically like carbolic acid, only more mildly. When heated with phthalic anhydride, it is converted into fluorescein (p. 493);. test for m-dihydroxy-benzenes), and it is therefore manufactured on the large scale. Nitrous acid or dia- zonium compounds transform it into azo-dyes ; with the latter it can yield mono-azo-dyes or primary Bis-azo-dyes (cf. p. 402). Its trinitro-derivative is styphnic acid, C 6 H(OH) 2 (N0 2 ) 3 , which is formed by the action of nitric acid upon many gum resins. Quinol, formerly called hydroquinone, p-dihydroxy -benzene (Wohler, 1844), may be obtained by the oxidation of quinic acid, C 7 H 12 6 , by means of Pb0 2 , by the hydrolysis of the glucoside arbutin, and from succinylo-succinic ester (cf. p. 241), &c. It is usually prepared by the reduction of quinone with sulphurous acid, and hence the name hydroquinone. It crystallizes in monoclinic plates or hexagonal prisms, of about the same solubility as its isomers, and may be TRIHYDRIC PHENOLS 419 sublimed. Ammonia colours it reddish-brown, while chromic acid, ferric chloride, and other oxidizing agents convert it into quinone or quinhydrone (p. 431). It melts at 169, and, being a strong reducing agent, it is used as a developer in photography. Lead acetate solution yields a white precipitate with a solution of catechol, but none with resorcinol, while quinol is only precipitated in presence of ammonia. From the observed heats of neutralization, resorcinol and quinol behave towards soda as dibasic acids, and catechol as a weak monobasic acid. Orcinol, or m-Dihydrwy-toluene, (CH 3 :OH:OH = 1:3:5), is found in many lichens (Rocella tindoria, Lecanora, &c.). It is formed by the elimination of carbon dioxide from or-sellinic acid, e.g. upon fusing extract of aloes with potash, and it can also be prepared synthetically from toluene (B. 15, 2992). Of especial interest is its synthesis from ethyl acetone-dicarboxylate (p. 260) and sodium (B. 19, 1446). It does not yield a fluor- escein with phthalic anhydride. Homo-catechol, C 6 H 3 (CH 3 )(OH) 2 , (CH 3 :OH:OH = 1:3:4), deserves mention on account of its mono-methyl ether creosol, CH 3 - C 6 H 3 (OH)(0 CH 3 ), occurring in beech-wood tar. Creosol is a liquid similar to guaiacol, boiling at 220, and, as a deri- vative of catechol, gives a green coloration with ferric chloride. Quinitol (Cydohexane -1:4- diol), p-dihydroxy - hexamethylene, C 6 H 10 (OH) 2 , a dihydroxy -derivative of reduced benzene, is ob- tained synthetically by the reduction of p-diketo-hexamethylene. It crystallizes in crusts, and has a sweet taste with a bitter after-taste; m.-pt. 144. It is the simplest representative of the inosite sugar group (p. 421). C. Trihydric Phenols Pyrogallol, Pyrogallic add (Sclieele, 1786), l:2:3-trihydroxy- benzene, is the most important of these three isomers.. It is obtained, apart from synthetical reactions, by heating gallic acid, when carbon dioxide is eliminated: C 6 H 2 (OH) 3 .C0 2 H = C 6 H 3 (OH) 3 + C0 2 . It crystallizes in white plates, melts at 132, is readily soluble in water, and capable of subliming without decom- position. It is an energetic reducing agent, e.g. for silver salts, and is used as a developer in photography. Its alkaline solution rapidly absorbs oxygen, hence its use in gas analysis. 420 XXIV. PHENOLS The aqueous solution is coloured bluish-black by a solution of ferrous sulphate containing ferric salt, and purple-red by iodine. It does not react with hydroxylamine (cf. Phloro- glucinol). Pyrogallol dimethyl ether, C 6 H S (OE)(OCH S ) 2 (Hofmann), is contained in beech-wood tar, as are likewise the dimethyl ethers of the compounds C 6 H 2 (CH 3 )(OH) 3 and C 6 H 2 (C 3 H 7 ) (OH) 3 , homologous with pyrogallol. Phloroglucinol, or l:3:5-Trihydroxy-benzene (Hlasiwetz, 1855), is obtained by the fusion of various resins and of resorciriol with potash or soda, by the action of alkali upon the gluco- side phloretin, and by fusing its dicarboxylic ester (whose synthetical formation is given on p. 439) with potash. It forms large prisms which weather in the air, melts at 218, and sublimes without decomposition. With ferric chloride it gives a dark-violet coloration, its solutions in alkalis readily absorb carbon dioxide, and it possesses reducing properties. Phloroglucinol is a typical example of a tautomeric com- pound. In many reactions, e.g. (a) the formation of metallic deriva- tives, C 6 H 3 (OK) 3 ; of a trimethyl ether, C 9 H 8 (OCH 8 ), which is insoluble in alkali; and of a triacetyl derivative, C 6 H 3 (OAc) 3 ; (b) its combination with phenyl-carbimide to form a tricarbani- line derivative, C 6 H 3 (0CONHC 6 H 5 ) 3 , it reacts as a normal phenol, i.e. as sym. trihydroxy-benzene. On the other hand, however, in certain of its reactions it behaves as a ketone, i.e. as triketo-hexamethylene, CO<^Qjj 2 ' < QQ^>CH 2 ; thus it yields a trioxime, C 6 H 6 ( : N OH) 3 , and when alkylated in presence of alcoholic potash yields tetra- and hexa-alkyl derivatives, e.g. * Its ultra-violet absorption rtrum (Hedley, J. C. S. 1906, 730) resembles that of other lols. Hydroxy-quinol, 1:2 -A- Trihydroxy-benzene, is obtained by fusing quinol with potash. Like pyrogallol, it yields no oxime with hydroxylamine. Hexahydroxy-benzene, Cg(OH) 6 , forms as its potassium salt potassium carboxide, C 6 6 K 6 , the explosive compound sometimes obtained in the manufacture of metallic potassium. It crystallizes in colourless prisms, has no definite melting- point, but decomposes at about 200, and can be converted into its quinone. AROMATIC ALCOHOLS 42 1 ftuercitol, CLH 7 (OH) 5 , found in the oak, and inosite or iiiositol, C 6 H 6 (OH) 6 , found in the muscles of the heart, are polyhydroxy-derivatives of hexamethylene. In many respects they closely resemble the aliphatic polyhydric alcohols rham- nitol and sorbitol. Quercitol melts at 235, is optically active, and has [a] D = -j-24'16. Inositol or hexahydroxy-cyclohexane exists in an inactive and in d-, /-, and r-modifications. , XXV. AROMATIC ALCOHOLS, ALDEHYDES, AND KETONES A. Aromatic Alcohols While the phenols remind us of the tertiary alcohols of the fatty series, although they differ from these in many points, we are acquainted with compounds which possess the alcoholic character in its entirety; they are termed aromatic alcohols. The most important of these is (primary) benzyl alcohol, C 7 H 7 OH, which is isomeric with the cresols, this isomerism being explained by the different position of the hydroxy-group in the molecule; thus, while the cresols, like all phenols, con- tain the hydroxyl linked to the benzene nucleus, in benzyl alcohol it is present in the side chain: CH 3 C 6 H 4 OH (cresols) C 6 H 6 CH 2 OH (benzyl alcohol). * This follows from the formation of benzyl alcohol from benzyl chloride, C 6 H 5 CH 2 C1 (and vice versa), and also from the fact that it can be oxidized to an aldehyde and an acid containing the same number of carbon atoms in the molecule as itself, these being likewise mono-derivatives of benzene : C 6 H 6 .CH 2 .OH C 6 H 5 .CHO C 6 H 5 .CO-OH Benzyl alcohol (Benzene- Benzaldehyde (Benzene- Benzoic acid (Benzene- methylol) methylal) carboxylic acid). Benzyl alcohol may also be looked upon as methyl alcohol in which one atom of hydrogen is replaced by the group C 6 H 5 : H CH 2 OH (carbinol) C 6 H 6 CH 2 OH (phenyl-carbinol), and is therefore the simplest aromatic alcohol. In addition to primary alcohols, e.g. tolyl alcohols, CH- C 6 H 4 .CH 2 OH, ^-phenyl-ethyl alcohol, C 6 H 6 CH 2 . CH 2 OH, 422 XXV. AROMATIC ALCOHOLS, ALDEHYDES, ETC. secondary, e.g. a-phenyl-ethyl alcohol, or l-pkenyl-hydroxy* ethane, C 6 H 5 CH(OH) CH 3 , and even tertiary alcohols, e.g. (C 6 H 5 ) 3 COH, triphenyl-carbinol, are known. Of the poly- hydric alcohols, phenyl-glycerol (l-phenyl-l:2:3-trihydroxy- propane) is the most important. All of these contain the hydroxyl radicals attached to carbon atoms of the side chain and not to those of the nucleus, and this is the fundamental difference between an aromatic alcohol and a phenol. The alco- hols are not of the same commercial importance as the phenols, and hence have not been investigated to the same extent. All these compounds are, as alcohols, perfectly analogous to the alcohols of the fatty series, so far as regards the formation of alcoholates, ethers, esters, mercaptans, amines, phosphines, &c. They are, however, at the same time benzene derivatives, and consequently yield chloro-, bromo-, nitro-, amino-, &c., substitution products. Unsaturated aromatic alcohols are also known, which resemble the unsaturated compounds of the fatty series to the closest extent in their chemical be- haviour, but are at the same time benzene derivatives. These remarks also apply in full degree, mutatis mutandis, to the aromatic aldehydes and ketones (see below). Benzyl alcohol, C 6 H 5 'CHo'OH, is a colourless liquid of faint aromatic odour, sparingly soluble in water, and boils at 204:. It occurs naturally in Peru and Tolu balsams as ben- zoic and cinnamic esters, and is formed from benzyl chloride just as alcohol is from ethyl chloride. It is usually prepared by the action of concentrated aqueous potash on benzaldehyde, whereby the one half of the aldehyde is oxidized and the re- mainder reduced (B. 14, 2394): 2C 6 H 5 .CHO + KOH = C 6 H 5 .CH 2 OH + C 6 H 6 .COOK. Benzyl alcohol is also formed when benzamide is reduced with sodium amalgam. This is a reaction which has been employed for the preparation of a number of substituted benzyl alcohols (Hutchinson, B. 1891, 24, 173). Phenyl-methyl-carbinol, C 6 H 5 . CH(OH) . CH 3 , b.-pt. 203, can be prepared by reducing acetophenone, C 6 H 5 CO-CH 3 (p. 427), into which it is reconverted by gentle oxidation. Numerous secondary and tertiary alcohols have been synthe- sized within recent years by means of Grignard's compounds (p. 356). The simplest of the unsaturated alcohols is cinnamic alco- hol, C 6 H 6 CH:CHCH 2 OH, which occurs as cinnamic ester AROMATIC ALDEHYDES 423 (" styracin ") in storax. It crystallizes in glistening needles of hyacinth-like odour, yields cinnamic acid when gently oxi- dized, and benzoic when the oxidation is more vigorous. B. Aromatic Aldehydes Benzaldehyde, Benzene-methylal, or oil of bitter almonds, C 6 H 5 -CHO, was discovered in 1803 and investigated by Liebig and W oliler (A. 22, 1). It is a colourless, strongly refracting liquid of agreeable bitter almond-oil odour. It boils at 179, has a sp. gr. 1*05 at 15, and is readily soluble in alcohol and ether, but only sparingly in water (1 in 30). The modes of formation are for the most part analogous to those described under the aliphatic aldehydes (pp. 122 and 123): (a) By the oxidation of the corresponding alcohol. This method, although of considerable practical importance in the aliphatic series, is of but theoretical interest in the aromatic, as the alcohols themselves are usually prepared from the aldehydes. (b) By the distillation of the calcium salt of the correspond- ing acid, benzoic acid, with calcium formate. (c) By heating the corresponding dichloride, benzal chloride, or benzylidene chloride, C 6 H 5 -CHC1 2 (from toluene), with water or sulphuric acid, or, as is done on the technical scale, with water and lime; also by heating benzyl chloride, C 6 H 5 CH 2 C1, with water and plumbous or cupric nitrate. This last method involves a process of hydrolysis : C 6 H 5 .CH 2 C1 C 6 H 6 .CH 2 .OH, and also a process of oxidation: C 6 H 5 .CH 2 .OH C 6 H 6 .C<^, both of which are brought about by the copper nitrate solu- tion. (d) Together with dextrose and hydrocyanic acid by decom- posing amygdalin, C 20 H 27 O n N, a glucoside (see Glucosides) which occurs in bitter almonds and crystallizes in white plates, either by means of sulphuric acid or by emulsin (an enzyme likewise present in bitter almonds, cf. pp. 267 and 592): C 20 H 27 U N + 2H 2 = C 6 H 5 .CHO + 2C 6 H 12 O 6 -f CNH. (e) By the action of chromyl chloride, Cr0 2 Cl 2 , upon toluene, 424 XXV. AKOMAT1C ALCOHOLS, ALDEHYDES, ETd. This is Etard's reaction, and is of great value for the synthesis of aldehydes and also of certain ketones from hydrocarbons. An additive compound, C 6 H 5 CH 3 (Cr0 2 Cl 2 ) 2 , is first formed, and yields the aldehyde on the addition of water (B. 17, 1462, 1700; 32, 1050. (/) ^7 the action of Grigiiard's phenyl-magnesium bromide on ethyl orthoformate (Bodroux, C. E. 1904, 138, 92 and 700), e.g.: C 6 H 6 .Mg.Br-f-CH(OEt) 3 = Mg-Br-OEt -f C 6 H 6 -CH(OEt) 2 . C 6 H 6 -CH(OEt) 2 hydrolysed C 6 H 6 .CHO. Gattermann and Maffezzoli (B. 1903, 36, 4152) have used Gri- gnard's compound with a large excess of ethyl formate at low temperatures.* (g) Homologues of benzaldehyde are sometimes prepared by the elimination of carbon dioxide from substituted phenyl- glyoxylic acids : C 6 H 4 X.CO-C0 2 H -* C 6 H 4 X.C^Q, a reaction which usually takes place when the glyoxylic acid is distilled. Behaviour. 1. Its behaviour is that of an aldehyde, and in many respects it closely resembles the aliphatic aldehydes. Thus it is (a) easily oxidizable to the acid, and on this account reduces an ammoniacal silver solution with the production of a mirror; (b) reducible to the alcohol; (c) capable of forming a crystalline additive compound with NaHS0 3 ; (d) capable of combining with HCN (see Mandelic acid); (e) capable of reacting with hydroxylamine and phenyl-hydrazine to benz- aldoxime, GgHg-CHiN-OH, and benzaldehyde-phenyl-hydra- zone, C 6 H 5 CH:N 2 H'CgH 5 , respectively; (/) converted into benzylidene chloride, C 6 H 6 -CHC1 2 , by the action of phosphorus pentachloride. 2. Benzaldehyde does not form an additive compound with ammonia analogous to the aldehyde-ammonias of the aliphatic series, but enters into a somewhat complex condensation, the oxygen of the aldehyde being eliminated with the hydrogen atoms of ammonia in the form of water, the complex conden- sation product hydrobenzamide being formed : 3C 6 H 6 .CHO + 2NH 3 = (C 6 H 5 .CH) 3 N 2 + 3H 2 O. 3. Benzaldehyde and its homoiogues can undergo poly- * For synthetical methods see Gattermann, A. 1906, 347, 347. REACTIONS OF ALDEHYDES 425 tnerization, e.g. when an alcoholic solution of benzaldehyde is boiled with potassium cyanide, benzoin is formed : C 6 H 6 .CH:0 + C 6 H 5 .CH:0 = C 6 H fi .CH(OH).CO.C 6 H 6 , a compound which is both a secondary alcohol and a ketone. 4. A number of condensation products can be obtained from the aromatic aldehydes, and many of these are of com- mercial importance. The condensation usually takes place in the presence of a condensing agent, e.g. acetic anhydride, anhydrous zinc chloride, potassic hydroxide, sodic ethoxide, &c. Among some of the simplest of these condensations are : (a) With primary amines. The formation of benzylidene anilines (Schifs Bases): = H 2 O + C 6 H 5 .CH:N.C 6 H 6 . It has been shown recently that this reaction is preceded by the formation of an additive compound, C 6 H 5 CH(OH)NH C 6 H 5 , which then passes into the benzylidene derivative. A few such additive compounds have actually been isolated. (Dimroth and Zoepritz, B. 1902, 35, 984.) (b) With tertiary amines, e.g. : 2C 6 H 5 .NMe 2 + C 6 H 5 .CHO = H 2 O + C 6 H 6 .CH(C 6 H 4 .NMe 2 ) 2 , when a substituted diamino-derivative of triphenyl-methane is produced (p. 483). (c) With the sodium salts of fatty acids, when unsaturated acids are formed (Perkin's Synthesis, pp. 441 and 442): C 6 H 6 CHO + CH 3 COONa = C 6 H 6 . CH : CH C0 2 Na + H 2 0. (d) With fatty aldehydes, ketones, &c. : C 6 H 6 .CH:0 + CHfc.CHiO = H 2 O + C 6 H 5 .CH:CH.CHO, when unsaturated aldehydes (e.g. cinnamic aldehyde) or ketones are formed. 5. Its reaction with alkalis (p. 422) is also different; in the fatty series aldehyde resins are formed, and with benz- aldehyde a mixture of primary alcohol and the corresponding acid. This latter reaction is characteristic of aldehydes in which the CHO group is directly attached to the benzene nucleus. 6. As a benzene derivative, it can be substituted by halogens (indirectly), and can be nitrated, sulphonated, &c. (directly). 426 XXV. AROMATIC ALCOHOLS, ALDEHYDES, ETC. As in the case of toluene, chlorine enters the side chain at the boiling temperature, with formation of benzoyl chloride, OJL.COC1. Among its derivatives, the following deserve mention : a-Benzaldoxime, Benz-anti-aldoxime, C 6 H B CH : N OH, is formed from benzaldehyde and hydroxylamine; it melts at 35, and decomposes when boiled. It can be transformed by means of acids into the isomeric /3-benzaldoxhne, benz-syn- 'aldoxime, which melts at 125 (for velocity, cf. Patterson, J. . S. 1907, 504; 1908, 1041), and in contradistinction to the isomer, readily reacts with acetic anhydride yielding benzo- nitrile. The oximes are stereo-isomeric (Nitrogen-isomerism). (Cf. pp. 138 and 428.) Benzaldehyde - phenyl - hydrazone, C 6 H 5 CH : N NHC 6 H 5 , forms colourless crystals, melting at 152. Benzylideneazine, CHPh : N N : CHPh, from benzaldehyde and hydrazine sul- phate, has m.-pt. 93. Nitro-benzaldehydes, N0 2 .C 6 H 4 .CHO. The m-compound is the chief product of nitration, but some 20 per cent of the o-compound is formed at the same time. The latter is best prepared by oxidizing o-nitro-cinnamic acid by KMn0 4 in pre- sence of benzene; it forms long colourless needles, melting at 46, yields indigo (p. 527) with acetone and caustic soda, and on exposure to sunlight forms o-nitroso-benzoic acid. It can be reduced to o-amino-benzaldehyde, NH 2 'CJE 4 CHO, a com- pound crystallizing in silvery glistening plates, m.-pt. 46, which is of value for various synthetical reactions. (See Quinoline; also B. 16, 1833.) m-Amino-benzaldehyde, which is prepared from w-nitro-benzaldehyde, by the reduction of its bisulphite compound, is used in the production of triphenyl- methane dyes. Cinnamic aldehyde, C 6 H 5 CH : CH CHO, is the chief con- stituent of oil of cinnamon (Persea cinnamomum), from which it may be isolated by means of its bisulphite-compound. It is an oil of aromatic odour, boils at 246, and is readily volatile with steam. In addition to its properties as an aldehyde, it also possesses the properties of an unsaturated compound, e g. forms a dibromide. Its reaction with potassium hydrogen sul- phite is characteristic. It first forms an additive compound, O 6 H 6 GH:CH.CH(OH)(S0 3 K), like an ordinary aldehyde, and then, as an unsaturated compound, combines with a second molecule of the sulphite, yielding C 6 H 5 CH(S0 3 K) CH 2 - H(OH)(S0 3 K) + 2H 2 0. (B. 24, 1805; 31, 3301.) AROMATIC KETONES 42? C. Aromatic Ketones The aromatic ketones are usually divided into (1) mixed aromatic ketones, viz. those which contain both an aryl and an alphyl group, e.g. CgH 5 CO'CH 3 , and (2) true aromatic or diaryl ketones, e.g. C 6 H 5 - CO C 6 H 5 . Acetophenone, Phenyl-methyl ketone, C 6 H 5 'COCH 3 , is the simplest representative of the mixed aromatic ketones. It crystallizes in colourless plates, is readily soluble in water, melts at 20, boils at 200, and is obtained by the normal modes of preparation for ketones, e.g. by distilling a mixture of acetate and benzoate of calcium, as also by the Friedel- Crafts' synthesis (p. 346), viz. the conjoint action of acetyl chloride and aluminium chloride upon benzene. When benzene and its derivatives are converted into ketones by this method, only one acyl group is introduced as a rule, and this into the para-position with respect to any alkyl group already present. With a sym. trialkylated benzene, e.g. mesitylene, it has been found possible to introduce two acyl groups, e.g. diacetyl- mesitylene, (CH 3 ) 3 6 H(COCH 3 ) 2 (V. Meyer, B. 1895, 28, 3212; 1896, 29, 846, 1413). When the temperature is kept low by diluting the mixture with carbon disulphide, a good yield of ketone may be obtained by the Friedel-Crafts' method. Acetophenone unites in itself the properties of a ketone of the fatty series and of a benzene derivative. It yields benzoic acid and carbon dioxide when oxidized with ordinary oxidizing agents, but with cold alkaline permanganate it yields C 6 H 5 - CO'C0 2 H, phenyl-glyoxylic acid or benzoyl-formic acid. When warmed with halogens, it is substituted in the side chain (e.g. to "phenacyl bromide", C 6 H 5 CO CH 2 Br), and with nitric acid it is nitrated. It is used as a soporific under the name of "Hypnone". Its oxime melts at 59, and its phenyl-hydrazone at 105. Although it combines with hydrogen cyanide to form the nitrile of a-phenyl-lactic acid, it cannot form an additive com pound with sodic hydric sulphite. Its homologues closely resemble it, but are liquid at the ordinary temperature. Acetophenone and some of its homo- logues can be prepared from hydrocarbons with long side chains by Etard's reaction (see p. 424; B. 23, 1070; 24, 1356). Aromatic poly ketones (cf. p. 221) have also been prepared, e.g.^ benzoyl-acetone, C 6 H 5 CO CH 2 CO CH 3 , and acetophenone- acetone, C 6 H 5 CO - CH 2 CH 2 CO CH 3 . The latter, like- 428 XXV. AROMATIC ALCOHOLS, ALDEHYDES, ETC. acetonyl-acetone, is readily converted into furane, pyrrole, and thiophene derivatives (see p. 516). Benzaldehyde condenses with acetone and acetophenone in the presence of alkalis, yielding unsaturated ketones, e.g. Benzylid- eneacetone, CHPh:CHCO-CH 3 , m.-pt. 41, and benzylidene- acetophenone, chakone, CHPh CH : CH CO C 6 H 5 , m.-pt. 58. Benzophenone, Diphenyl ketone, C 6 H 5 CO C 6 H 5 , may be obtained (1) by distilling calcium benzoate, (2) by the Friedel- Crafts' synthesis, (3) by the oxidation of diphenylmethane, (C 6 H 5 ) 2 CH 2 , or of diphenyl-carbinol, (C 6 H 5 ) 2 CH OH. Good yields of ketones are not usually obtained by the action of Grignard's reagents on acid chlorides; as a rule the reaction proceeds further, and a tertiary alcohol is obtained (p. 356). An exception is found in the reaction between a-naphthyl-magnesium bromide and benzoyl chloride. Ketones have recently (Blaise, C. R 1901, 132, 38; 133, 299) been synthesised from Gh'ignard's reagents and nitriles, e.g. : R-CN + B/.Mg.I = RR'CiNMgl, and this with water gives: R.CO-R' + NH S + I-Mg-OH. Acid amides react in a somewhat similar manner. Benzophenone is dimorphous; the stable modification melts at 49, and when boiled or distilled yields the unstable modi- fication, melting at 26; but this gradually passes back again into the stable modification. The reaction is, however, con- siderably accelerated by the addition of a minute crystal of the stable compound. It yields an oxime melting at 140 and a phenyl-hydrazone melting at 105. When reduced with zinc dust or hydriodic acid and red phosphorus, it yields diphenylmethane. Stereo-isomeric Oxirnes and Hydrazones. The isomerism described on pp. 137 et seq. is more frequently met with in the aromatic than in the aliphatic series. Benzaldehyde and most of its substitution products yield two distinct oximes and most of the unsymmetrical aromatic ketones, e.^..^?-chloro-benzo- phenone, 6 H 4 C1 CO C 6 H 6 , and tolyl-phenyl-ketone, CH 3 C 6 H 4 COC 6 H 5 , also yield stereo-isomeric oximes of the syn- and anti- types. The one isomeride is usually readily trans- formed into the more stable by means of hydrochloric acid or bromine, by rise of temperature, and by exposure to light. HYDROXY-ALCOHOLS, ETC. 429 The following relationships of the benzaldoximes are of interest: Benz-cwfo'-aldoxime * Benz-awft'-aldoxime hydrochloride f heated J heated Benz-syn-aldoxime * Benz-sytt-aldoxime hydrochloride. HC1 The syn- or anti- configuration of the isomerides is determined in the case of the aldoximes by a comparison of the readiness with which water is eliminated and a nitrile formed, and in the case of the ketoximes by an examination of the products obtained by Beckmanris transformation (p. 139). Thus: C 6 H 5 .C.C 6 H 4 .CH 3 gives C G H 6 .CO.NH.C 6 H 4 .CH 3 " Benz-#-toluidide Phenyl-^-tolyl-antt-ketoxime and C 6 H 6 .C.C 6 H 4 .CH 3 gives CH 3 .C 6 H 4 .(X).NH.C 6 H 6 " Anilide of jp-toluic acid. Phenyl-jj-tolyl-sj/n-ketojcime Compare Henrich, B. 1911, 44, 1533. D. Hydroxy or Phenolic Alcohols, Aldehydes, and Ketones Formula. Name. Constitution. OH.C 6 H 4 .CH 2 OH Saligenin, or o-hydroxy-benzyl alcohol. OCH 3 .C 6 H 4 .CH 2 OH Anisyl alcohol, or _p-methoxy-benzyl alcohol. OH C 6 H 3 (OCH 8 ) . CH 2 OH .... Vanillic alcohol, or 3-methoxy-4-hydroxy-benzyl alcohol. OH C 6 H 3 (OCH 3 ) (C 8 H 4 OH).. Coniferyl alcohol, [OCH S :OH = 3:4]. OH.C 6 H 4 .CHO :.... Salicyl-aldehyde, or o-hydroxy-benzaldehyde. OCH 8 .C 6 H 4 .CHO Anisaldehyde, or >-methoxy-benzaldehyde. (OH) 2 C 6 H 3 CHO Procatechuic aldehyde, or 3 : 4-dihydroxy-benzaldehyde. OH.C 6 H 3 (OCH 3 ).CHO Vanillin, or 3 - methoxy - 4 - hydroxy - benz- aldehyde. CH 2 2 : C C H 3 CHO Piperonal, artificial heliotrope or methylene-protocatechuic al- dehyde. A large number of compounds are known which possess 430 XXV. AROMATIC ALCOHOLS, ALDEHYDES, ETC. phenolic properties in addition to those of an alcohol, aldehyde or ketone. They are derived from the simple alcohols, &c., by the entrance of hydroxyl into the benzene nucleus. Several of these compounds occur in nature, e.g. saligenin is a constituent of salicin (see the Glucosides), while salicylic aldehyde is found in Spiraea varieties and vanillin, in vanilla capsules. Anisaldehyde is obtained from the oxidation of anisole (methyl phenyl ether). An extremely interesting synthesis of hydroxy-aldehydes is by the Tiemann-Eeimer reaction. This consists of heating a phenol with chloroform in the presence of concentrated potas- sium hydroxide : C 6 H 6 .OK + CHC1 3 = HC1 + CHC1 2 .C 6 H 4 .OK, and the dichlor-derivative thus formed is hydrolyscd by the alkali to CHO.C 6 H 4 .OK. The formyl-group -CH:0 always takes up the o- or ^-position with respect to the hydroxy- group, and, as a rule, the o- and jp-compounds are formed together, and may often be separated by the difference in volatility of the two compounds in steam. Vanillin crystallizes in beautiful needles, and is prepared on the large scale from coniferin, C 16 H2 2 8 -f- 2H 2 0, a com- pound occurring in the sap of the cambium in the Coniferse. This is hydrolysed by acids into glucose and coniferyl alcohol, C 6 H 3 (OH)(pCH 3 )(C 3 H 4 .OH), and the latter yields vanillin when oxidized (Tiemann and Haarmann) ', the CH 3 group is removed by heating with hydrochloric acid at 200, with the formation of protocatechuic aldehyde. Vanillin is also found in asparagus, raw beet-sugar, and asafcetida, and it likewise results from the oxidation of olive wood, &c. Vanillin can also be obtained synthetically from m-chloro- />-nitro-benzaldehyde (from m-chloro-^-nitro-toluene). E. Quinones Quinones are compounds derived from benzene and its derivatives by the replacement of two atoms of hydrogen by two of oxygen, e.g. C 6 H 4 2 . As a group they are characterized by (a) their yellow colour, (b) being readily reduced to dihydric phenols, and hence often acting as oxidizing agents. They are often divided into para-quinones, in which the two oxygen atoms are in the ^-position, and ortho-quinones, in which they are in the 0-position. ^-BENZOQUINONE 431 ^-Benzoquinoae or Quinone, C H 4 2 (1838), is produced when chromic acid is added to a solution of quinol. It crys- tallizes in yellow needles or prisms of a characteristic pungent odour something like that of nut-shells, is sparingly soluble in water but readily in alcohol and ether, and can be sublimed; m.-pt. 116. Corresponding with it we have a large number of higher homologues, &c. These also are solids, mostly of a yellow colour, and are volatile with r steam; they are obtained by the oxidation of the corresponding dihydroxy-phenols, or of polyhydric pnenols, which contain two hydroxyls in the para-position. Quinone is also formed by the oxidation of many aniline and phenol derivatives belonging to the para-series, e.g. ^-amino-phenol, sulphanilic acid, and >-phenol-sulphonic acid; it is usually prepared by the oxidation of aniline itself by means of chromic acid (see B. 1887, 20, 2283). It was first obtained by distilling quinic acid with manganese dioxide and sulphuric acid. Exposure to light causes it to turn brown, and it colours the skin yellow-brown. It is readily reduced to quinol by S0 2 , HI, SnCl 2 and HC1, &c., and can therefore act as an oxidizing agent. In chloroform solution it takes up two or four atoms of bromine to form a di- or tetra-bromide (C 6 H 4 2 Br 4 ). Under other conditions chlorine and bromine act upon it as substi- tuents, while hydrochloric acid forms chloroquinol : C 6 H 4 2 + HC1 = C 6 H 3 C1(OH) 2 . It yields sparingly soluble crystalline compounds with primary amines, and also coloured compounds with phenols. With quinol it forms an additive compound termed quin- hydrone, C 6 H 4 2 + C 6 H 4 (OH) 2 ; this crystallizes in green prisms with a metallic lustre, and is also formed as an inter- mediate product in the oxidation of quinol or in the reduction of quinone. Its constitution has not been definitely settled. (Cf. Siegnunds, J. pr. 1911, 83, 553; also Knorr, B. 1911, 44, 1503.) Constitution. Quinone is derived from benzene by the ex- change of two atoms of hydrogen for two of oxygen, which, from the close connection between quinone and quinol, must be in the ^-position. The constitution of quinone may be explained either by assuming that these two oxygen atoms are linked together, as in peroxide of hydrogen, H0-0H, so that the benzene nucleus remains unchanged, or that the 432 XXV. AROMATIC ALCOHOLS, ALDEHYDES, ETC. latter experiences a partial reduction, with the formation of a derivative of C 6 H 8 , a " diketo-dihydro-benzene " : C CO CH .0 HC/NCH According to the first of these two formulae, quinone would be a peroxide ; according to the second, a ketone. In favour of the latter view (which was brought forward by Fittig, and is now almost universally accepted) are (1) the fact that qui- none can be converted into an oxime, C 2 H ^ 22 (identical with nitroso-phenol, p. 414), and into a dioxime, quinone dioxime, C 2 H 2 <^;oS>C 2 H 2 (B. 20, 613); (2) its power of forming additive compounds with bromine; and (3) its relations to the analogously constituted anthraquinone. (Of. B. 18, 568; A. 223, 170; J. pr. Ch. 42, 161. Also chapter on Physical Properties and Constitution.) Tetrahydro-quinone, p-Diketo-hexamethylene (cyclo-hexane-l-A- dione), CH 2 .CO.CH 2 CH 2 .CO-CH 2 ' can be prepared by hydrolysing and eliminating the carboxyl groups from succinylo-succinic ester (p. 343). It crystallizes in colourless prisms, melts at 78, and, on reduction, yields quinitol (p. 419). (Cf. B. 22, 2168; 23, 1272.) Chloranil, Tetrachloro-quinone, CgCl 4 2 , which crystallizes in lustrous yellow plates, is obtained by chlorinating quinone and also by oxidizing many organic compounds, e.g. phenol, with HC1 and KC10 3 . A good yield may be obtained by chlorinat- ing |?-nitraniline, reducing the 2 : 6-dichloro-4-nitraniline thus obtained to 2 : 6-dichloro-^-phenylene-diamine, and then oxidiz- ing and chlorinating by means of potassic chlorate and hydro- chloric acid: N 2 C 6 H 4 NH 2 -* N0 2 - C 6 H 2 C1 2 NH 2 C 6 H 2 C1 2 (NH 2 ) 2 -> C 6 C1 4 O 2 (Witt. Abstr. 1904, 1, 174.) When reduced, it yields the colourless tetrachloro-quinol; it also acts as an oxidizing agent, converting e.g. dimethylaniline into methyl-violet. A dilute QUINONES 433 solution of potassium hydroxide transforms it into potassium chloranilate, C 6 C1 2 2 (OK) 2 + H 2 (dark-red needles), corre- sponding with which there is also an analogous nitro-compound, potassium nitranilate, C 6 (N0 2 ) 2 2 (OK) 2 . The latter salt is dis- tinguished by its sparing solubility, hence its formation may be made use of as a test for potassium compounds. (For its constitution, see B. 19, 2398.) Chlorine transforms chloranil and chloranilic acid into com- plex chloro-products of the hexa- and pentamethylene series, and finally into chlorinated fatty compounds. (For a tabular summary, see Hantzsch, B. 22, 2841; cf. also B. 25, 827, 842.) Toluquinone, C 6 H 3 (0 2 )(CH 3 ), xyloquinone, C 6 H 2 (O 2 )(CH 3 ) 2 , thymoquinone, C 6 H 2 (0 2 )(CH 3 )(C 3 H T ), &c., are known. Several of these can be prepared synthetically by the condensation of 1:2 diketones; for instance, diacetyl yields xyloquinone under the influence of alkali (cf. B. 21, 1411 and p. 342): CHa-rCOj-CO-CHiHi: _ CH^C-CO-CH " HC.CO-C.CH 3 4 2 ' 0-Benzoquinone, CO\IT ^ ^^' ^ some " c w ^ tne j9-compound, has been recently prepared by Willstatter and Pfannenstiel (B. 1904, 37, 4744) by the oxidation of an ethereal solution of catechol (0-dihydroxy-benzene) with silver oxide. It forms pale-red transparent plates, is relatively unstable, and begins to decompose at 60-70. It is readily reduced by sulphur dioxide to catechol, and dyes the skin brown. For two isomeric forms, cf. B. 1908, 41, 2580; 1911, 44, 2632. F. Quinone Chlorimides, Quinone Aniles, and Anilino-quinones A number of nitrogen derivatives closely related to the quinones are known. As examples, we have C 6 H 4 ^Q ' , quinone chlorimide; C fi H 4 Cxrni> quinone dichlorimide ; NT OH C 6 H 4 ^ , quinone oxime, and the corresponding dioxime; < l uinone anile ; and C 6 H 4N.*C 6 H 5 ' ( l uinone dianile. The quinone chlorimides are obtained by the oxidation of the ^-amino-phenols or ^>-phenylene-diamines with bleaching (B480) 8l5 434 XXV. AROMATIC ALCOHOLS, ALDEHYDES, ETC. powder, e.g. quinone chlorimide, 0:CgH 4 :NCl, from ^-amino- phenol hydrochloride, and quinone dicnlorimide, C1N:C 6 H 4 : NC1, from ^-phenylene-diamine hydrochloride. The first- named crystallizes in golden-yellow crystals, which are volatile with steam; when reduced it yields amino-phenol, and when boiled with water quinone; the dichorimide reacts similarly. Quinone monoxime, obtained by the action of hydroxyl- amine hydrochloride on quinone (H. Goldschmidt, B. 1884, 17, 213), is identical with the compound obtained by the action of nitrous acid on phenol, or by the hydrolysis of ^-nitroso- dimethyl-aniline, and previously termed ^-nitroso-phenol. It would appear to have the oxime constitution 0:CgH 4 :N'OH, as with hydroxylamine it yields the dioxime OHN:C 6 H 4 : N'OH, and when alkylated yields ethers of the type 0:C 6 H 4 : N-OK. (Cf. also Hartley, J. C. S. 1904, 1016.) Quinone monanile is obtained by oxidizing j9-hydroxy-di- phenylamine, OH C 6 H 4 NH CgH 5 , and forms fiery-red crys- tals melting at 97; with aniline it yields dianilino-qumone anile, : C 6 H 2 (NHPh) 2 : NPh. The dianile is obtained by- oxidizing diphenyl - p - phenylene - diamine, C^H 4 (NHPh) 2 ; it melts at 175-180, and its dianilide, viz. dianilino- quinone dianile, NPh : C 6 Ho(NHPh) 2 : NPh, is most readily obtained by heating p-nitroso-dimethyl-aniline with aniline and aniline hy- drochloride. Such anilino-quinone aniles are usually termed azophenines (Fischer and Hepp, A. 1889, 256, 257; 1890, 262, 247). The important groups of aniline dyes known as indo- phenols and indamines are respectively hydroxy- and amino- derivatives of these aniles, e.g. phenol blue is (CH 3 ) 2 NC 6 H 4 N : C 6 H 4 : 0, and is obtained by oxidizing a mixture of amino- dimethyl-aniline and phenol; the corresponding a-naphthol de- rivative, NMe 2 C 6 H 4 N:C 10 H 7 :0, is an important blue dye. G. Pseudo-phenols. Methylene-quinones Numerous phenolic alcohols react with halogen hydracids yielding the corresponding esters of the alcohols, e.g. : OH.C 6 H 3 Br.CH 2 .OH OH.C 6 H 3 Br.CH 2 Br, OH.C 6 Br 2 Me 2 .CH 2 .OH - OH.C 6 Br 2 Me 2 -CH 2 .Br; but the products thus obtained are insoluble in alkalis, and are characterized by the reactivity of the bromine atom in the CH 2 Br group. The compounds have been termed by Auwers pseudo-phenols, and they are usually regarded as o- or ^-quinone AROMATIC ACIDS 435 derivatives, e.g. the two compounds mentioned above are repre- sented as Such compounds readily react with alkalis, losing hydrogen bromide and yielding methylene - quinones of the type 0:C 6 H 3 Br:CHo; the majority of these are unstable, and im- mediately yield condensation products which are insoluble in alkalis (cf. Auwers, A. 301, 203; B. 32, 2978; 34, 4256; 36, 1878; 39, 435; Zincke, A. 320, 145; 322, 174; 329, 1; 353, 335, 357). XXVI AROMATIC ACIDS The aromatic acids are analogous to the fatty acids in most respects. As acids they are capable of forming exactly the same kinds of derivatives as the latter, e.g. metallic salts, esters, chlorides, anhydrides, amides, &c.: As benzene derivatives they yield chloro-, bromo-, iodo-, hy- Iroxy-, nitro-, amino-, and sulphonic acid derivatives, &c., e.g.: C 6 H 4 C1-CO 2 H (chloro-benzoic acids); NH 2 'C 6 H 4 'CO 2 H (amino-benzoic acids); OH-S0 2 -C 6 H 4 .CO 2 H (sulpho-benzoic acids); OH'C 6 H 4 CO 2 H (hydroxy-benzoic acids); C H 6 -CH(OH).CO 2 H (mandelic acid); &c. Constitution. Corresponding with the aromatic acids there are nitriles, e.g. with benzoic acid, benzo-nitrile, C 6 H 5 C:N, which may also be regarded as cyanogen derivatives of the lydrocarbons (in the above case, cyano-benzene), and which, m hydrolysis, yield the i acids. From this, and from their general properties, it follows that their constitution must ;orrespond exactly with that of the fatty acids; like the atter they are characterized by the presence of carboxyl, CO* OH, in the molecule. There are monobasic, di-, tri-, and up to hexabasic aromatic acids, according to the number )f hydrogen atoms in the molecule which are readily re- )laceable by metallic radicals, i.e. according to the number of jarboxyl groups: C 6 H 4 (C0 2 H) 2 C 6 H 3 (C0 2 H) 3 C 6 (CO 2 H) 6 Phthalic acids Benzene-tri-carboxylic acids Mellitic acid. 436 XXVI. AROMATIC ACIDS Numerous unsaturated aromatic acids are known. As un- saturated compounds, they readily form additive compounds with hydrogen, chlorine, hydrogen iodide, and are thereby converted into saturated acids or their substitution products. In most of these additions the benzene nucleus remains un- altered. Their constitution is therefore entirely analogous tc that of the acids of the acrylic or propiolic series; they contain a side chain with a double or triple carbon bond : C 6 H 6 CH : CH C0 2 H C 6 H 5 C : C - CO 2 H Cinnamic acid Phenyl-propiolic acid. In addition to the aromatic acids proper, which have just been mentioned, other acids have been prepared recently, which are derivatives either of a completely reduced or a partially reducea benzene molecule. The acids of the former series, e.g. the hexa hydro-benzoic acids, have properties very similar to those oJ the saturated fatty acids; while those of the latter, e.g. the di- and tetrahydro-benzoic acids, resemble the unsaturated fatty acids. (Cf. p. 349.) The aromatic hydroxy-acids, e.g. the hydroxy-benzoic acids, which are both phenols and acids, manifestly contain phenolic hydroxyl (i.e. hydroxyl which is linked directly to the ben zene nucleus) in addition to the carboxyl group or groups they are capable of yielding salts either as acids or as phenols, but otherwise they correspond in many points with the ali phatic hydroxy-acids. The true aromatic hydroxy-acids, such as mandelic acic (phenyl-gly collie acid), which correspond completely with the aliphatic hydroxy-acids, manifestly contain their alcoholic hy droxyl not in the benzene nucleus, but in the side chain, as is also the case with the aromatic alcohols. Nomenclature. One of the simplest systems of nomenclature is the designation of the aromatic acids as carboxylic acidi of the original hydrocarbons in question, e.g. phthalic acid it benzene-1 : 2-dicarboxylic acid. Many names, such as xylic acid, are taken from those of the hydrocarbons into whicl the carboxyl has entered, while others, such as mesitylenic acid, indicate the hydrocarbons from which the acids an obtained by oxidation. An important principle as regards nomenclature depends upon the fact that aromatic acids car be derived from almost every fatty acid of any consequence by the exchange of H for C 6 H 6 , e.g. : CH 3 CO 2 H (acetic acid) C 6 Hg - CH 2 CO 2 H (phenyl-acetic acid). FORMATION OF AROMATIC ACIDS 437 There thus exist phenylated acids analogous to the acids of the acetic, glycollic, succinic, malic, and tartaric series, &c. For example, atropic acid, C 6 BL'C(C0 2 H):CH 2 , may be desig- nated a-phenyl-acrylic acid, ana cinnamic acid, C 6 H 6 CH : CH C0 2 H, /5-phenyl-acrylic acid. Properties. Most of the aromatic acids are solid crystalline substances, generally only sparingly soluble in water, and therefore precipitated by acids from solutions of their salts, but often readily soluble in alcohol and ether. The simpler among them can be distilled or sublimed without decom- position, while the more complicated, especially phenolic and polycarboxylic acids, evolve carbon dioxide when heated; e.g. salicylic acid, OH C 6 H 4 C0 2 H, breaks up into phenol and C0 2 . The elimination of carbonic anhydride from those acids which volatilize without decomposition may be effected by heating with soda-lime; in poly basic acids the carboxyls may be successively decomposed : C 6 H 4 (C0 2 H) 2 = C 6 H 6 C0 2 H + C0 2 Occurrence. A large number of the aromatic acids are found in nature, e.g. in many resins and balsams, and also in the animal organism in the form of nitrogeneous derivatives such as hippuric acid (benzoyl-glycocoll), C 6 H 5 CO NH CH 2 C0 2 H. Modes of Formation. A. Of the saturated acids : 1. By the oxidation of the corresponding primary alcohols or aldehydes, e.g. benzoic acid from benzyl alcohol, or from benzaldehyde. 2. One of the commonest methods of obtaining aromatic acids is by the oxidation of benzene homologues. Each alkyl group present in the nucleus of the hydrocarbon can be oxi- dized to a carboxylic group, whether it be long or short, e.g. both C 6 H 5 .CH 3 and C 6 H 5 .CH 2 .CH 2 .CH 3 yield C 6 H 5 .C0 2 H. All substituted benzene homologues which contain the sub- stituent in the side chain are similarly oxidized to non-substi- tuted aromatic acids, e.g. C 6 H 5 -CH 2 C], C 6 H 5 .CH 2 -NH 2 , and C 6 H 5 .CH:CH.C0 2 H yield C 6 H 5 .C0 2 H. A substituted benzene homologue which contains halogen, nitro-, sulpho-, amino-, hydroxy-, &c., substituents attached to the benzene nucleus, yields a similarly substituted aromatic acid, e.g.-. C 6 H 4 C1.CH 3 C 6 ELC1.CO 2 H; (OH) 2 C 6 H 3 .CH 3 (OH) 2 .C 6 H 3 .C0 2 H; NO 2 .C 6 H 4 .CO 2 H. N0 2 -C 6 ] Should there be several side chains in the molecule, they 438 XXVI. AROMATIC ACIDS are usually all converted directly into carboxyl by chromic acid; whereas by using dilute nitric acid, this transformation can be effected step by step, e.g. : C 6 H 4 (CH 3 ) 2 yield first C 6 H 4 (CH 3 )(CO 2 H) and then C 6 H 4 (CO 2 H) 2 The xylenes Toluic acids Phthalic acids. Nevertheless, the three classes of isomeric benzene deriva tives with two side chains comport themselves differently. The para-compounds are the most readily oxidized to acids by chromic acid mixture, and then the meta-; whereas the ortho compounds are either completely destroyed by it (p. 348), or not attacked at all. The last-named may, however, be oxi- dized in the normal manner by nitric acid or potassic perman- ganate. The entrance of a negative group or of hydroxyl into the o-position with respect to the alkyl radical renders the oxi- dation more difficult (cf. p. 416). 3. By the hydrolysis of the corresponding nitriles : C 6 H 6 .CN-f-2H 2 = C 6 H 5 -CO 2 H-fNH 3 . These nitriles, which can be prepared from the ammonium salts of the acids in the same manner as those of the fatty series, are often obtained by the following syntheses: (a) By distilling the potassic salts of the sulphonic acids with potassic cyanide or ferrocyanide (Merz\ just as the nitriles of the fatty acids are formed from the potassium alkyl-sulphates (p. 100): C 6 H 6 .S0 3 K Nitriles cannot, as a rule, be prepared from KCN and aro matic halogen derivatives which contain the halogen attached to the nucleus (cf. p. 355); the halogen is more readily re- placed by cyanogen if sulphonic acid or nitro-groups are like- wise present: C 6 H 4 Br.N0 2 + KCN = CN.C 6 H 4 -N0 2 + KBr. Benzyl chloride, C 6 H 5 'CH 2 C1, and all the haloid hydro- carbons which are substituted in the side chain, on the other hand, react with potassic cyanide in the manner characteristic of the alphyl haloids : C 6 H 6 .CH 2 C1 + KCN = KCl-f C 6 H 6 .CH 2 -CN Benzyl cyanide. (b) By diazotizing the primary amines and replacing the diazo-group by cyanogen, according to Sandmeyer's reaction FORMATION OF ACIDS 439 (p. 388). This reaction is frequently made use of in the preparation of substituted benzo-nitriles, e.g. 2 : 4-dibromo- benzo-nitrile, CgH^FoCN, and the isomeric 2 : 6 -compound, also of tolu-nitriles, CH 3 -C 6 H 4 .CN. (c) By heating the mustard oils (phenyl-iso-thiocyanates, p. 276), with copper or zinc dust (ffreitti): C 6 H 5 .N:C:S + 2Cu = C 6 H 6 .C:N + Cu 2 S. (d) By the molecular transformation of the isomeric iso- nitriles at a somewhat high temperature: C 6 H 6 .N:C C 6 H 6 .C:N. (e) By eliminating the elements of water from the oximes of the aldehydes by means of acetyl chloride (pp. 137 and 429): Benzaldoxime, C 6 H 6 CH : N . OH = C 6 H 6 CN -f H 2 O. 4. By the reduction of unsaturated acids, thus hydrocinnamic by the reduction of cinnamic acid with sodium amalgam find water, or with hydrogen and finely divided Palladium : C 6 H 6 .CH:CH.CO 2 H + 2H = C 6 H 5 .CH 2 .CH 2 -CO 2 H. The acids obtained by this method always contain the C0 2 H group attached to a side chain. Similar acids can also be ob- tained by the reduction of hydroxy-, bromo-, or keto-acids, where the OH, Br, CO, and C0 2 H are all in side chains, e.g. : C 6 H 5 .CH(OH).CO 2 H C 6 H 5 .CH 2 .CO 2 H. 5. A number of syntheses of nucleus carboxylic acids can be accomplished. These may be regarded as the more or less direct introduction of the carboxylic group into the benzene nucleus, and are usually effected by means of carbonic acid derivatives. In many cases the yields are only small, and the reactions are mainly of theoretical interest. (a) Benzoic acid and its homologues are produced by the action of carbon dioxide upon bromo-benzenes, &c., in presence of sodium (Kehttt) : C 6 H 6 Br + CO 2 + 2Na = C fl H 6 .CO 2 Na + NaBr. (b) By the action of phosgene, COC1 2 , upon benzene and its homologues in presence of A1C1 3 (Friedel and Crafts) : COC1 2 = C 6 H 6 .COC1 440 XXVL AROMATIC ACIDS Acid chlorides are first formed, but can be readily decomposed by water. By the further action of these chlorides upon benzene in presence of A1C1 3 , ketones are formed (see Benzo-phenone). Carbonyl chloride reacts most readily with tertiary amines: = (CH 3 ) 2 N.C 6 H 4 .COC1 (c) By the action of carbamic chloride, C1-CO-NH 2 , upon benzene (or phenol) in presence of A1C1 3 , amides of the aro- matic acids are formed, and these can be hydrolysed (Gaiter- man, B. 1899, 32, 1116): C 6 H 6 -fCl.CO.NH 2 = C 6 H 6 .CO-NH 2 (d) By the action of sodium upon a mixture of a brominated benzene and ethyl chloro-carbonate (Wurtz); in this case the esters are first formed, but these are readily hydrolysed: 6 + NaBr -f NaCl. (e) The phenolic acids are formed by passing carbon dioxide over heated sodium phenates (Kolbe-, see Salicylic acid): In the case of the polyhydroxy-phenols, e.g. resorcinol, an acid is often formed by merely heating the phenol with a solution of ammonium carbonate or potassium bicarbonate (B. 13, 930). (/) jo-Hydroxy-acids are formed by the action of carbon tetrachloride upon phenols in alkaline solution (B. 10, 2185; Tiemann-Beimer reaction; cf. p. 430): C 6 H 6 .ONa + CC1 4 = C 6 H 4 (OH).CC1 3 + NaCl. C 6 H 4 (OH).C0 2 Na + SNaCl -f 2H 2 0. (g) By heating the sulphonates with sodium formate (V. Meyer) : C 6 H 6 .S0 3 Na + HCO 2 Na = C 6 H 6 -C0 2 Na -j-HS0 3 Na. (h) By the action of carbon dioxide on ethereal solutions of organo-magnesium compounds (Grignard's reagents), and sub- sequent treatment with acids: C 6 H 6 .Mg.Br + C0 2 -> C 6 H 6 .CO 2 'MgBr C 6 H 6 .CO 2 H. 6. Syntheses by the aid of ethyl aceto-acetate and ethyl malonate. Ethyl aceto-acetate reacts with the halide derivatives which are substituted in the side chain, e.g. benzyl chloride, exactly FORMATION OF ACIDS as in the fatty series, with the formation of the more com- plicated ketonic acids, which again are capable of undergoing either the "acid hydrolysis" or the "ketone hydrolysis" (p. 226), e.g.-. C 8 H 6 CHoCl + CH, CO CHNa CO 2 Et = CH 3 .CO.CH(CH 2 C 6 H 6 ).C0 2 Et + Benzyl-aceto-acetic ester. CH 3 .CO.CH(CH 2 .C 6 H 5 ).C0 2 Et -f 2H 2 O = C 6 H 6 .CH 2 .CH 2 .C0 2 H + CH 3 .C0 2 /3-Phenyl-propionic acid. Ethyl phloroglucinol dicarboxylate, (OH) 3 C H(C0 2 Et) 2 , may be synthesised by heating ethyl sodio-malonate with ethyl malonate at 145 (Movre, J. C. S. 1904, 165). 7. Hydroxy-acids and keto-acids are formed by exactly the same methods as in the fatty series (pp. 205 and 206), e.g. mandelic acid by the combination of hydrogen cyanide with benzaldehyde, and hydrolysis of the nitrile thus formed (B. 14, 239,1965): C 6 H 5 .CHO + HCN = C 6 H 5 .CH(OH).CN; or from phenyl-chloro-acetic acid (B. 14, 239): = C 6 H 5 .CH(OH).CO 2 H + KC1. B. The following are some of the commoner methods em- ployed for the preparation of unsaturated acids: 1. From the mono-haloid substitution products of the satu- rated acids by the elimination of halogen hydracid (cf. p. 163); also from the corresponding nitriles, primary alcohols, &c., as in the case of the saturated compounds. 2. According to the so-called Perkin synthesis, by the action of aromatic aldehydes upon the sodium salts of fatty acids in the presence of a condensing agent, usually acetic anhydride. Thus, when benzaldehyde is heated with acetic anhydride and sodium acetate, cinnamic acid is formed : The acetic anhydride probably acts as a dehydrating agent in this instance, the reaction taking place between the sodium acetate and the aldehyde (cf. A. 216, 101). Hydroxy-acids are formed as intermediate products by a reaction similar to the "aldol condensation" (p. 131); in the above case, for instance, -phenyl-hydracrylic acid, C 6 H 5 . CH(OH) . CH 2 . C0 2 H. 442 XXVI. AROMATIC ACIDS When the sodium salt and the anhydride of two different acids, e.g. sodic propionate and acetic anhydride, are used, the product varies with the conditions (B. 1901, 34, 918), but usually consists of a mixture of two unsaturated acids. This reaction also takes place with the hydroxy-aldehydes, with the homologues of acetic acid, and also with dibasic acids, e.g. malonic; but all acids employed must contain a CH 2 group in the a-position with respect to the C0 2 H, e.g. : C 6 H 5 .CH:0 + CH 3 .CH 2 .C0 2 Na = H 2 O-f C 6 H 6 .CH:C(CH 3 ).C0 2 H a-Methyl-cinnamic acid. It is a very general mothod used for the preparation of <x:/?-unsaturated acids; in certain cases, e.g. a-phenyl-cinnamic acid, C 6 H 5 CH:C(C 6 H 5 )C0 2 H, and its nitro-derivatives, two stereo-isomerides are produced corresponding with the two cro- tonic acids or with fumaric and maleic acid. Unsaturated monobasic acids are also formed when aromatic aldehydes are heated with malonic acid in presence of ammonia, aniline, or other amines (Knoevenagel) : C 6 H 6 .CH:'O'+H2;C(CO 2 H) 2 = C 6 H 6 -CH:C(CX) 2 H) 2 = C fl H 5 - CH : CH C0 2 H + CO^ The esters of these acids are formed when aromatic aldehydes are condensed with the esters of fatty acids in the presence of sodium ethoxide (Claisen, B. 23, 976; cf. Claisen condensation, p. 224). 3. Uinnamic acid is also formed by the action of benzal chloride upon sodium acetate (Caro): = C 6 H 5 .CH:CH.C0 2 H + 2HC1. 4. By the action of aceto-acetic ester upon the phenols in presence of concentrated H 2 S0 4 , unsaturated phenolic acids or their anhydrides (B. 16, 2119; 17, 2191) are formed, e.g.: (Pseudo-form) Methyl-cumarin. A. Monobasic Aromatic Acids Constitution and Isomers. The cases of isomerism in the aromatic acids are easy to tabulate. An isomer of benzoic acid is neither theoretically possible nor actually known. Carboxylic acids of the formula C 8 H 8 2 may, however, be MONOBASIC AROMATIC ACIDS 443 . OO C<1 t-i SH ?-< T* CCJ ."beo ; 3 00 Ci CO <$< 00 U3 : i i CO ^^fcJS 1 r r S3 <??. ooooooo <M GO Crt 01 t oooooo CO oooo <? ^-t CO O ?-" O O5 jfiOS ?-l 2- OO ?- O1 ' *" ^ * ^ * ^ . 888 m 000 o T3 o.2 o i-sfw S i 8 a,MHi j, g a." g r 8 H 8 : :<5<5 ^3!^ oo ^ ill^^lS^^l^i I ^ ?9 9oo o'' !i ' I 3 f K & g 11 I 35 : ;a i8 a 4s" ^ TS 03 00 ( ^^ llll tfeMa 1 S o o -< Iti^. iWtflg^ 1 M oooo I! Van m 444 XXVI. AROMATIC ACIDS derived from toluene by the entrance of carboxyl either into the benzene nucleus or into the side chain, thus : o-m-p- C 6 H 6 .CH 2 .C0 2 H Phenyl-acetic acid. The nature of their oxidation products yields proof of their constitution, the former yielding the phthalic acids, and the latter benzoic. Of acids C 9 H 10 2 , a large number of isomers are already known (see table). Hydrocinnamic acid and hydratropic acid are phenyl-propionic acids, the former ft- and the latter a-, corresponding with the lactic acids; the isomeric relations of the fatty acids thus repeat themselves here. The tolyl-acetio acids, CH 3 -CgH 4 -CH 2 -C0 2 H, and the ethyl-benzoic acids, C 2 H 5 C 6 H 4 C0 2 H, stand in much the same relation to each other as aceto-acetic acid, CH 3 CO CH 2 C0 2 H, to propionyl- formic acid, CoH 6 CO C0 2 H, and they all yield phthalic acids when oxidized. Lastly, mesitylenic acid and its isomers are dimethyl-benzoic acids, and are oxidizable to benzene-tricarb- oxylic acids. As instances of isomers among the unsaturated acids, we may take cinnamic and atropic acids (analogous to ft- and a-chlor- acrylic acids, p. 168). Further, the hydroxy-toluic acids, C 6 H 3 (CH 3 )(OH)(C0 2 H), are isomeric with mandelic acid, C 6 H 5 'CH(OH)-COoH, the former being oxidized to hydroxy-phthalic acids, C 6 H 3 (OH) (C(XH) 2 , and the latter to benzoic acid; the hydrocoumaric acids, CgIL 3 , are likewise isomeric with tropic acid. The first-named yield hydroxy-benzoic acids on oxidation, and the last benzoic. Differences are apparent, e.g. in respect to reducibility, according as the carboxyl is linked directly to the nucleus or to a side chain; the amides of the respective acids are in the former case reduced to the corresponding alcohols, but not in the latter. (Of. B. 24, 173.) 1. MONOBASIC SATURATED ACIDS Benzoic acid, C 6 H 5 -C0 2 H, was discovered in gum benzoin in 1608, and prepared from urine by Scheele in 1785. Its composition was established by Liebig and Wohlei^s classical researches in 1832. It occurs in nature in gum benzoin, from which it may be obtained by sublimation ("acidum benzoicum ex resina"); also in dragon's-blood (a resin), in Peru and Tolu balsams, in castoreum, and in cranberries. I* BENZOIC ACIDS 445 is present in the urine of horses in combination with glycocoll as hippuric acid, from which it may be obtained by hydrolysis with hydrochloric acid ("acidum benzoicum ex urina"). It is obtained on the large scale ("ac. benz. ex toluole") as a by-product in the manufacture of oil of bitter almonds from benzyl chloride or benzal chloride. The acid may also be formed by heating benzo-trichloride with water to a some- what high temperature: C 6 H 6 .CC1 3 C 6 H 6 .qOH) 3 C 6 H 6 .CO.OH. Benzoic acid is also present in coal-tar. It crystallizes in colourless glistening plates or flat needles, sublimes readily, and is volatile with steam; its vapour has a peculiar irritating odour, and gives rise to coughing. It melts at 121, boils at 250, and is readily soluble in hot water, but only sparingly in cold. When heated with lime, it is decomposed into benzene and car- bon dioxide. It is used in medicine and in the manufacture of aniline blue. Some of its salts crystallize beautifully, e.g. cal- cium benzoate, (C 6 H 5 C0 2 ) 2 Ca -f- 3 H 2 0, in glistening prisms. From the partially or wholly reduced benzene molecule there are derived (a) the dihydro-benzoic acids, C 6 H 7 'C0 2 H, of which five are theoretically possible, according to the position of the double linkings, viz. A-l:3-, A-l:4-, A-l:5-, A-2:4-, and A-2 : 5-dihydro-benzoic acids, but only two known (B. 1891, 24, 2623, and 1893, 26, 454); (b) the tetrahydro- benzoic acids, C 6 H 9 C0 2 H, all three of which are actually known, viz. A-1-, A-2-, and A-3-tetrahydro-benzoic acids (A. 271, 231); and a hexahydro-benzoic acid, C 6 H n C0 2 H (hexa- Tnethylene-carboxylic acid), which is found in the petroleum from Baku, and which can also be prepared from benzoic acid. The Esters, e.g. methyl benzoate, C 6 H 5 .C0 2 CH 3 , b.-pt. 199, and ethyl benzoate, C 6 H 5 .C0 2 C 2 H 5 , b.-pt. 213, are always prepared by the catalytic method of esterification (p. 174), namely, by boiling the acid for three to four hours with a 3-per-cent solution of dry hydrogen chloride or of concentrated sulphuric acid in the requisite alcohol (E. Fischer and Speier, B. 1895, 28, 3252). They may also be obtained by the other general methods for the preparation of esters : (a) by the action of an acid chloride on the alcohol alone, or in presence of alkali (Schotten, Baumanri) or of pyridine (Emhorn and Hollandt, Abstr. 1899, 1, 577); (b) by the action of an alkyl iodide on the silver salt of the acid; and (c) by the action of alkyl sulphates, more especially methyl sulphate, on aqueous solu- 446 XXVI. AROMATIC ACIDS tions of the alkali salts of the acids (Werner and Seybold, B. 1904, 37, 3658). These esters are liquids of pleasant aromatic odour which boil for the most part without decomposition, and frequently serve for the recognition and estimation of alcohols. They may be hydrolysed in much the same mariner as the aliphatic esters, although as a rule not so readily. Benzyl benzoate, C 6 H 6 C0 2 -CH 2 'C 6 H 5 , is present in the balsams of Peru and Tolu. Benzoyl chloride, C 6 H 5 .CO-C1 (LieUg and jrtiMer), ob- tained by the action of phosphorus pentachloride on the acid, is the complete analogue of acetyl chloride, but more stable than the latter, since it is only slowly hydrolysed by cold water, although quickly by hot. It is a colourless liquid boiling at 198, and has a most characteristic pungent* odour. It is prepared technically by chlorinating benzaldehyde. Benzole anhydride, (C 6 H 5 'CO) 2 (Gerhardt\ is exactly analogous to acetic anhydride. It crystallizes in prisms in- soluble in water, boils without decomposition, and becomes hydrated on boiling with water. M.-pt. 39. In addition to the ordinary anhydrides or oxides, peroxides of the type benzoyl peroxide or benzo-peroxide, C 6 H 5 CO0- CO C 6 H 5 , are known. They may be obtained by the action of the acid chloride on a cooled solution of sodic peroxide (B. 1900, 33, 1575, and C. C. 1899, 2, 396). Benzo-peroxide crystallizes from alcohol in prisms, melts at 106-108, is relatively stable, and is insoluble in water. When its ethereal solution is mixed with sodic ethoxide, the products formed are ethyl benzoate, and the sodic salt of perbenzoic acid, C 6 H 6 .CO'O.OH, a hygroscopic acid melting at 41-43. It has a strong odour resembling hypochlorous acid, is readily volatile, but decomposes violently when heated, and is a strong oxidizing agent Many aliphatic and aromatic acids yield similar derivatives. Benzamide, CgH^CO-NHg, corresponds with acetamide, and is prepared from benzoyl chloride and ammonia or ammonium carbonate. It forms lustrous, nacreous plates, melting at 130, boils without decomposition, and is readily soluble in hot water. The amido-hydrogen of benzamide may be substituted by alkyl radicals such as phenyl, &c., with the formation, e.g. of benzanilide, C ? H 5 CCKNHC 6 II 5 , the anilide of benzoic acid, a compound which can be readily prepared from aniline and benzoic acid, or aniline and benzoyl chloride. It crystallizes in colourless plates, melts at 158, distils unchanged, and is in BENZOIC ACID DERIVATIVES 447 fact the complete analogue of acetanilide, but is much more difficult to hydrolyse, fusion with potash being one of the best methods. Thio-benzamide, C 6 H 5 .CS-NH 2 , is obtained by the union of benzo-nitrile with hydrogen sulphide, or by heating benzyl- amine with sulphur. Benzoyl-hydrazine, Benzhydrazide, C 6 H 5 -CO.NH.NH 2 , ob- tained from ethyl benzoate and hydrazine hydrate, melts at 112, and with nitrous acid yields benzoyl-azimide, benzazide, N || , which yields benzoic and hydrazoic acids on N" hydrolysis. (Cf. Curtius, Abstr. 1895, 1, 32.) Metallic derivatives of benzamide are also known, e.g. ben- zamide silver. Titherley (J. C. S. 1897, 468; 1901, 407) has shown that the silver derivative exists in two forms : a white l^TTT compound, which is stable and is probably C 6 H 5 *C<T;^ , and UAg an unstable orange compound, C 6 H 5 CO NH Ag. These two metallic derivatives correspond with the pseudo and normal formulae for benzamide, viz. C 6 H 5 -(X%vTT and CgHg-CO'NH^ From the pseudo form are derived imino-ethers (cf. p. 185). Hippuric acid, Benzamino-acetic acid, C 6 ILCO'NHCH 2 C0 2 H, is an amino-derivative of benzoic acia, being derived from the latter and glycocoll (amino-acetic acid); it may be prepared by heating benzoic anhydride with glycocoll (B. 17, 1663), and is present in the urine of horses and of other her- bivora. When benzoic acid or toluene is taken internally, it is eliminated from the system in the form of hippuric acid. It crystallizes in rhombic prisms, sparingly soluble in cold water but readily in hot, decomposes when heated, and forms salts, esters, nitro-derivatives, &c. When hydrolysed with con- centrated hydrochloric acid it yields glycocoll hydro'chloride and benzoic acid. Benzo-nitrile, C 6 H 5 CN (cf. p. 438), is an oil which smells like oil of bitter almonds, and boils at 191*. It is prepared either by the action of PC1 5 upon benzamide (p. 183), or by distilling benzoic acid with ammonium thiocyanate. It pos- sesses all the properties of a nitrile, combining slowly with nascent hydrogen to benzylamine, readily with halogen hydride to an imino-chloride, with amines to amidines (p. 1 87 ; cf . A. 192, 1), with hydroxylamine to amidoximes (p. 188). 448 XXVI. AROMATIC ACIDS Substituted Benzole Acids. The hydrogen atoms of ben- zoic acid are replaceable by halogen with the formation e.g. of chloro-benzoic acid, 6 H 4 C1C0 2 H. In such formation of mono-substitution products the halogen takes up the meta- position with respect to the carboxyl. Nitric acid (especially a mixture of nitric and sulphuric acids) nitrates it readily, w-nitro-benzoic acid being the chief product, together with a smaller quantity of the ortho- and a very little of the para-acid. The o- and ^-halogen and nitro-compounds are usually pre- pared by indirect methods, e.g. : o-CH 3 .C 6 H 4 .N0 2 C0 2 H.C 6 H 4 .NO 2 or 2:4-C 6 H 3 Br 2 .NH 2 -* C 6 H 3 Br 2 .CN - C 6 H 3 Br 2 .CO 2 H. In the preceding pages attention has been drawn repeatedly to the influence which a radical, already present in the benzene molecule, exerts on the position taken up by a second radical entering the molecule. As examples we have: CeHjBr * ^-C 8 H3r 2 ; CeH 5 -OH * o-o-2>-C 6 H 2 Br 8 -OH. C 6 H 5 .NO a - m-CoH^NOsk; C 6 H 5 .NH 2 -* o-o-p-C 6 H 2 Br 8 -NH 2 . C,H 6 .S0 8 H m-C 8 H4(SO,H) 2 ; C 6 H 5 .CHO w-N0 2 -C 6 H 4 .CHO. C 6 H 5 CH 8 * o- and p-CH 8 CeH* N0 2 . The following broad generalizations will be found to apply to most cases: I. If the radical already present is Cl, Br, I, OH, NH 2 , 01 CH 3 , then, by the introduction of Cl, Br, I, N0 2 , or S0 3 H radicals, para- and to a certain extent ortho-compounds are formed, and only very exceptionally meta-compounds. II. If the radical present is NO,, SOgH, OHO, or C0 2 H, then, on chlorination, bromination, nitration, or sulphonation, meta-compounds are formed. (See Crum Brown and Gibson, J. C. S. 1892, 367. For details cf. Obermuller ; Hollemann, Die Direkte Einfiihrung von Substituenten, 1910.) In many reactions all three isomeric products have been isolated, but in very different quantities; thus at benzoic acid yields 80*2 per cent of m- t 18'5 of o-, and only 1*3 of jp-nitro-benzoic acid; at 30 nitrobenzene yields 91 per cent of m-, 8 of 0-, and 1 of p-dinitro-benzene. It is probable that the three isomerides are also formed in other cases which have not been examined so carefully. The temperature at which the substitution occurs also appears to determine to a certain extent the relative proportions of the isomers formed. INFLUENCE OF SUBSTITUENTS 449 The substituted benzole acids closely resemble benzoic acid, and yield similar derivatives. The strengths of the different acids largely depend upon the nature of the substituents and their positions with respect to the carboxylic group. Acid. M.-p. K. Benzoiq 121 0*006 o-Methyl-benzoic 105 0*012 w-Methyl-benzoic 110 0*00514 p-Methyl-benzoic 180* 0'00515 o-Bromo-benzoic 150 0*145 wi-Bromo-benzoic 155 0*0137 jo-Bromo-benzoic 251 o-Nitro-benzoic 148 0*616 m-Nitro-benzoic 141 0*0345 jp-Nitro-benzoic 240 0*0396 o- Ammo-benzole 145 O'OOl Ttt-Ammo-benzoic 176 0*003 ^- Ammo-benzole 186 0*001 Ethyl ester. M.-p. B.-p. 211 220 225 228 254 259 30 47 57 13 89 267 294 The numbers for K given in the table indicate that the introduction of negative radicals, e.g. N0 2 , Br, &c., more especially into the ortho-position, markedly increases the strength of the acid, whereas the introduction of positive radicals, e.g. the amino-, more especially into ortho-positions, tends to weaken the acid (cf. p. 168). Chemical Retardation and Influence of Substituents (cf. p. 175). Within recent years a number of examples of the retardation or complete inhibition of chemical reactions by the presence of ortho-substituents have been discovered. One of the best known examples of this is met with in the esterifi- cation of aromatic acids by the hydrogen chloride catalytic method. Kellas (Zeit. Phys. Chem., 1897, 24, 221) has shown that even one ortho-substituent, whether it be CH 3 , N0 2 , Br, &c., retards the formation of ester; and V. Meyer and Sudborough (B. 1894, 27, 510, 1580, and 3146) have shown that when two such ortho-substituents are present an ester is not formed at all.* The cause of this retardation and inhibition is now generally supposed to be due to the fact that in the formation of an ester an additive compound of the acid and alcohol, + CH 3 .OH = + H a O. * Esters of such acids can be prepared by heating the acids with alcohol to high temperatures. (8480) 2? 450 XXVI. AROMATIC ACIDS is first formed, that this compound then decomposes into the ester and water, and that the spatial arrangements are such that ortho-substituents are so close to the carboxylic group that they interfere with the formation of an additive com- pound, and thus retard or inhibit esterification (Wegscheider). In confirmation of this view we have the fact that 0-substituents do not interfere to nearly the same extent when the carboxylic group is removed some distance, e.g. by the interposition of a chain of carbon atoms. The acid, _ Br/~ YCH 2 .CH 2 . s-tribromo-hydrocinnamic acid, for example, is readily esterified under the usual conditions. Other cases of chemical retarda- tion due to o-substituents have been met with in the hydro- lysis of substituted benzo-nitriles; compounds like ON CN cannot be hydrolysed to the corresponding acids by the usual methods. Di-ortho-substituted benzoyl chlorides and benz- amides and % benzoic esters are also remarkably stable and difficult to hydrolyse to the acids (Sudborough, Ira Remsen). Di-ortho-substituted ketones, COE CH cannot be converted into oximes (F. Meyer), and di-ortho- substituted tertiary amines, N(CH 3 ) 2 cannot yield quaternary ammonium salts (p. 379) (E. Fischer). That ortho-substituents do not retard or inhibit all chemical actions is shown by the fact that esters of di-ortho-substituted INFLUENCE OF SUBSTITUENTS 451 benzoic acids may be obtained by other methods, viz. the action of the alcohol on the acid chloride, and the action of alkyl iodide on the silver salt of the acid, or of methyl sul- phate on an alkali salt of the acid. In certain reactions the presence of ortho-substituents ap- pears to favour or accelerate a chemical reaction; examples of this are to be met with in the diacetylation of arylamines (Sudb&rough, J. C. S. 1901, 79, 533) and in the chemical re- activity of picryl chloride, 2 and similar compounds. The reactivity of various substituents, such as 01, NH 2 , &c., which are in the o- or ^-position with respect to a nitro-group, has been noted previously (pp. 362, 374, 414). A simple explanation of this reactivity may be due to the formation of an o- or jp-quinonoid additive product. Thus in the action of alkalis on 0-nitraniline : NH . \/ NH > \/M>K 2 \/ K where the NH 2 group is replaced by OK, an ortho-quinonoid compound may be formed as indicated above, and this by the loss of ammonia would yield the potassic derivative of 0-nitro- phenol. The amino-benzoic acids, NH 2 C 6 H 4 C0 2 H, which are ob- tained by the reduction of the nitro-acids with tin and hydro- chloric acid, &c., are interesting, as they are both bases and acids, i.e. amphoteric, and therefore similar to glycocoll in chemical character; they combine with hydrochloric acid, chloro-platinic acid, &c., as well as reacting with mineral bases to yield metallic salts. With regard to their consti- tution, cf. Glycocoll, p. 212. With nitrous acid they yield diazo- benzoic acids, C 6 H 4 <^QQ /, which correspond with the diazo -benzene- sulphonic acids. 0-Amino-benzoic acid is also obtained from phthalimide, by the Hofmann reaction (cf. Amides, b 452 XXVI. AROMATIC ACIDS haviour of, par. 5), and by the oxidation of indigo with man- ganese dioxide and caustic soda, and is often termed anthra- nilic acid; it forms (in contradistinction to the m- and #-acids) r-\r\ an intramolecular anhydride, anthranil, C 6 H 4 <^jj^>, and is an important intermediate product in the synthesis of indigo. The methyl ester is an important constituent of the essential oil of orange-blossom. The sulpho-benzoic acids, OH . S0 2 . C 6 H 4 . CO . OH, are di- basic acids. An ammonia derivative of o-sulpho-benzoic acid QO is the sweet substance "saccharine", C 6 H 4 <^Q 2 ^>NH, i.e. 0-sulpho-benzimide, or 0-benzoyl-sulphone-imide, an imide com- parable with succinimide. It is a white crystalline powder, almost three hundred times as sweet as cane-sugar, and is used to some extent in place of the latter. Acids, C 8 H 8 2 . 1. The three toluic acids, CH 3 .C 6 H 4 .C0 2 H, can be prepared from the three xylenes. ^-Toluic acid is ob- tained from ^-toluidine, by transforming it according to the Sandmeyer reaction into ^-cyano-toluene and hydrolysing the latter (A. 258, 9). Isomeric with them is 2. Phenyl - acetic acid, a -Toluic acid, C 6 H 5 CH 2 C0 2 H (Cannizaro, 1855). This acid differs characteristically from its isomers by its behaviour upon oxidation (see p. 444). It may be obtained synthetically from benzyl chloride and potassium cyanide, benzyl cyanide, C 6 H 5 CH 2 .CN (b.-pt. 232), being formed as intermediate product; it crystallizes in lustrous plates, melts at 76, and boils at 262. It is capable of undergoing substitution either in the benzene nucleus or in the side chain. In the latter case there are formed compounds such as Phenyl-chloracetic acid, CgH 5 CHCl-C0 2 H, and phenyl- amino-acetic acid, C 6 H 5 CH(NH 2 ) C0 2 H, compounds which possess precisely the same character as mono-chloracetic and amino-acetic acids. Isomeric with phenyl-amino-acetic acid are the three amino-phenyl-acetic acids, NH 2 C 6 H 4 CH 2 C0 2 H, of which the 0-acid is interesting on account of its close relation to the indigo group. It does not exist in the free state, but forms an intramolecular anhydride, oxindole (p. 522): Such formation of an intramolecular anhydride is of very HOMOLOGUES OF BENZOIO ACID 453 frequent occurrence in ortho-amino-compounds of this kind, in contradistinction to the m- and ^-compounds (see Indole). Theoretically, it may take place in the above instance in two different ways, viz. either by the elimination of a hydrogen atom of the ammo-group together with OH of the carboxyl, or of both of the amino-hydrogen atoms with the oxygen atom from the carbonyl group. These two cases are distinguished by Baeyer as " Lactam formation " and " Lactim formation ". Oxindole is the lactam of o-amino-phenylacetic acid, isatin, C 6 H 4 <^>>CO (P- 523 )> tne lactam of o-amino-phenylgly- oxylic acid, NH 2 .C 6 H 4 -CO.CO.OH, and carbostyril (p. 456), /N=COH C 6 HX , the lactim of o-amino-cinnamic acid. x/H : CH Both lactams and lactims contain hydrogen which is readily replaceable; in the former case it is present in the amino- group, and in the latter in the hydroxyl. If the compounds which result from the replacement of hydrogen by alkyl are very stable, the alkyl in them is linked to the nitrogen, and they are derivatives ol the lac- tams; if, on the contrary, they are easily saponifiable, the alkyl is linked to oxygen, and they are ethers of the lactims. Many lactams and lactims react as tautomeric substances (cf. Isatin and chapter on Constitution and Physical Properties). Acids, C 9 H 10 2 . 1. Dimethyl-benzole acids, Xylene-carloxylic acids, C 6 IJ 3 Me 2 C0 2 H. Of these six are possible, and four are known. Mesitylenic acid, (C0 2 H : CH 3 : CH 3 = 1:3:5), is prepared by the oxidation of mesitylene. Isomeric with them are 2. The Phenyl-propionic acids. /3-Phenyl-propionic acid or hydrocinnamic acid, C G H 5 CH 2 CH 2 'C0 2 H, is prepared by reducing cinnamic acid with sodium amalgam, or with hydrogen in presence of colloidal palladium, and is also formed during the decay of albuminous matter. It crystallizes in slender needles; m.-pt. 48, b.-pt. 280. Many substitution products of this acid are known, among which may be mentioned o-nitro- cinnamic acid dibromide, N0 2 .C 6 H 4 .CHBr.CHBr.C0 2 H, a compound nearly related to indigo (p. 523); further, phenyl-a-amino-propionic acid (phenyl-alanine), C H 5 .CH 2 .CH(NH 2 ).C0 2 H, and phenyl-/?- amino-propionic acid, C 6 H 5 .CH(NH 2 ).CH 2 .C0 2 H, both of which can be prepared synthetically, the former being like- 454 XXVT. AROMATIC ACIDS wise produced during the decay of albumen and during the germination of Lupinus luteus. o-Amino-hydrociniiainic acid, C 6 H 4 <^ H 2 < QQ H , is not stable, but is immediately transformed into its lactirn, hydro- carbostyril, C 6 H 4 <^ - , a quinoline derivative. ^CH 2 CH 2 Hydratropic acid, a-Phenyl-propionic acid, CH 3 CH(C 6 H 5 ) C0 2 H, is obtained as its name implies by the addition of hydrogen to atropic acid. It is liquid and volatile with steam. 2. MONOBASIC UNSATURATED ACIDS 1. Cinnamic acid, C 6 H 5 CH : CH . C0 2 H (Trommsdorf, 1780), occurs in Peru and Tolu balsams and also in storax, and may be prepared as given at p. 441. It crystallizes in needles or prisms, dissolves readily in hot water, melts at 133, and boils at 300. When fused with potash, it is split up into benzoic and acetic acids; it also yields benzoic acid when oxidized. It yields salts, esters, &c.j also additive compounds, with chlorine, bromine, hydrogen chloride, bromide, iodide, and also with hydrogen and hypochlorous acid, e.g. cinnamic acid dibromide (/?-phenyl-a-/3-dibromo-propionic acid), C 6 H 5 'CHBr. CHBr-C0 2 H. Further, the hydrogen in the benzene nucleus may be replaced by Cl, Br, N0 2 , NH 2 , &c. Cinnamic acids. According to the ordinary stereo-chemical theory of unsaturated compounds, two cinnamic acids of the formula C 6 H 5 CH : CH C0 2 H should exist (cf. Maleic and Fumaric acids, p. 243). Two have been known for some time, viz. storax-cinnamic acid, melting at 134, and a//o-cin- namic acid, melting at 68, prepared by reducing /?-brom-allo- cinnamic acid with zinc and alcohol. But, in addition to these, several other cinnamic acids have been described (for summary see Erhnmeyer, Biochem. Zeitsch. 1911, 34, 306): (a) Lieber- mann's iso-cinnamic acid (B. 1890, 23, 141, 512), melting at 5S-59; this occurs naturally together with the allo acid in cocaine alkaloids, and may also be obtained by fractionally crystallizing the brucine salt of allo-cinnamic acid (B. 1905, 38, 2562), and decomposing with acid, or by the action of an alcoholic solution of zinc bromide on allo-cinnamic acid (B. 1905, 38, 837). (b) Erlenmeyer's iso-cinnamic acid, melting at 37-38, and obtained by reducing a-brom-allo-cinriamic acid with zinc and alcohol (A. 1895, 287, 1; B. 1904, 37, 3361) CINNAMIC ACIDS 455 (c) Triclinic cinnamic acid, melting at 80. (d) Hetero-cin- namic acid, rn.-pt. 131. The synthetical acid prepared by Perkin's method is, according to Erlenmeyer (Abs. 1911, i, 782), a mixture of storax- and hetero-acids, and can be separated by fractional precipitation of the sodium salt by hydrochloric acid or by fractional distillation of the ethyl ester. It is probable that the allo- and two eso-acids are trimorphous forms of the same substance (Biilmann, B. 42, 182, 1443). They appear to give the same melt as shown by examination of refractive indices (Stobbe), and solubilities (Meyer), and also to give the same solutions as shown by their electrical conduc- tivities (Bjerum, B. 43, 571), and absorption spectra (Stobbe, ibid., 504). Any one of the three acids can be obtained from the melt by impregnating under suitable conditions with a crystal of the desired form; and even the solids are mutu- ally transformable (Stobbe, B. 44, 2735; Meyer, 2966). According to Eiiber and Godschmidt (B. 43, 453) the hetero- acid is an impure form of the storax-acid, but this is denied by Erlenmeyer (Abs. 1911, i, 782), who also claims to have prepared optically active cinnamic acids (ibid., 781), the mole- cules of which must be asymmetric. No satisfactory explana- tion of the existence of so many isomerides has been offered so far. Although some six cinnamic acids are known, only two a-bromo-cinnamic acids and two /?-bromo-cinnamic acids have been prepared. The a-bromo- and a-brom-allo-cinnamic acids are obtained by the elimination of hydrogen bromide from cinnamic acid dibromide: C 6 H 6 CHBr CHBr C0 2 H - HBr = C 6 H 6 CH : CBr CO 2 H, or its esters, and they melt respectively at 131 and 120. The corresponding /3-acids can be prepared by the addition of hydrogen bromide to phenyl-propiolic acid: CfiHjj.C-C.COaH + HBr = C fl H 6 .CBr:CH.CO 2 H. .They melt respectively at 135 and 159. (Compare Sudborough and Thompson, J. C. S. 1903, 666, 1153; Sudborough and Lloyd, ibid., 1898, 91; Sudborough and Roberts, ibid., 1905, 1841; Sud- borough and James, ibid., 1906, 105; James, 1911, 1620. o- and _p-Nitro-cinnamic acids, NOg-CgH^CHzCH the first of which is of importance on account of its relation to indigo, are obtained by the nitration of cinnamic acid. 456 XXVI. AROMATIC ACIDS On reduction the former yields o-amino-cinnamic acid, which readily yields its lactim carbostyril (a-hydroxy-quinoline), ")H:CH =C.OH The radical of cinnamic acid, i.e. (C 6 H 6 CH : CH CO ), is termed " cinnamyl ", and the group (C 6 H 5 CH : CH ) " cinnamenyl". 2. Atropic acid, CH 2 : C(C 6 H 5 ) C0 2 H, is a decomposition product of atropine. It crystallizes in monoclinic plates, and can be distilled with steam. It breaks up into formic and a-toluic acids when fused with potash. 3. (y)-Phenyl-isocrotonic acid, C 6 H 5 . CH : CH . CH 2 . C0 2 H, is formed when benzaldehyde is heated with sodium succinate and acetic anhydride (W. H. Perkin, sen., also Jayne, A. 216, 100): C 6 H 6 -CHO -f CH 2 (CO 2 H).CH 2 .CO 2 H - H 2 O Oxi UJjL^vA^.tly ^-ti 2 6 co = CO 2 + C 6 H 5 .CH:CH.CH 2 .CO 2 H. It is of interest on account of its conversion into a-naphthol (see this), C 10 H 7 OH, upon boiling. 4. Phenyl-propiolic acid, C 6 H 5 .C:C.C0 2 H (Glaser, 1870), is prepared from cinnamic acid dibromide or its ethyl ester by first converting into a-brom-cinnamic acid by elimination of hydrogen bromide, and then into the acetylenic acid by further elimination (just as ethylene is converted by bromine into ethylene bromide, and the latter decomposed into acety- lene by potash). It crystallizes in long needles, and melts at 136-137. When heated with water to 120, it breaks up into C0 2 and phenyl-acetylene (p. 353). It can be reduced to hydrocinnamic acid and transformed into benzoyl-acetic acid. 0-Nitro-phenyl-propiolic acid, N0 2 C 6 H 4 C C C0 2 H (Baeyer), is prepared in a manner analogous to that just given, viz. by the addition of bromine to ethyl 0-nitro-cinnamate and treatment of the resulting bromide with alcoholic potash (A. 212, 240). It is of interest on account of its relation to indigo (see p. 626). It breaks up into C0 2 and 0-nitro-phenyl-acety- lene when heated. 3. SATURATED PHENOLIC ACIDS (For modes of formation, see p. 440.) These acids may also be obtained by the oxidation of the homologues of phenol PHENOLIC ACICS 467 and of the hydroxy-aldehydes, which is effected, among other methods, by fusion with alkalis. The phenolic acids form salts both as carboxylic acids and as phenols, salicylic acid, for instance, the two following classes : )H and Mono- and Di-sodium salicylate. The first of these two salts is not decomposed by C0 2 , while the second, as the salt of a phenol, is decomposed by it and converted into the first. The phenolic acids behave, therefore, like monobasic acids towards sodium carbonate. When both of the hydrogen atoms are replaced by alkyl, there are formed compounds such as C 2 H 5 CJH 4 C0 2 C 2 H 6 , which, as both ethers and esters, are only half hydrolysed when boiled with potash, e.g. to C 2 H 5 C 6 H 4 C0 2 H, ethyl salicylic acid. The ether acids thus formed possess completely the character of monobasic acids, their alphyl radical being only eliminated by hydriodic acid at a rather high temperature. (Cf. p. 412.) The 0-hydroxy-acids (C0 2 H:OH =1:2) are, in contradis- tinction to their isomers, volatile with steam, give a violet or bhie coloration with ferric chloride, and are readily soluble in cold chloroform. The m-hydroxy-acids are more stable than the o- and ^-com- pounds; while most of the latter break up into carbon dioxide and phenols when quickly heated, or when acted on by hydro- T chloric acid at 220, the former remain unaltered. The phenolic acids are much more easily converted into halogen or nitro-substitution products than the monobasic acids, just as the phenols are far more readily attacked than \the benzene hydrocarbons. v Salicylic acid, o-Hydroxy-lenzoic add (C0 2 H:OH = 1:2), was discovered by Piria in 1839. It occurs in the blossom of Spiraea Ulmaria, and as its methyl ester in oil of winter-green, &c. It may be obtained by the oxidation of the glucoside saligenin; by fusing coumarin, indigo, 0-cresol, &c., with potash; by diazotizing o-amino-benzoic acid, &c. (see p. 387). Preparation. Sodium phenoxide is heated in a stream of carbon dioxide at 180-220 (Kolbe, A. 113, 125; 115, 201, &c.), when half of the phenol distils over and basic salicylate of sodium remains behind: C 6 H 6 ONa + CO 2 = OH C 6 H 4 CO JSTa ; 2 Na + C 6 H 6 .ONa = ONa.C 6 H 4 .(X) 2 Na -f C 6 H 6 -OH. 4:58 XXVI. AROMATIC ACIDS Should potassic phenoxide be used instead of the sodic com- pound, salicylic acid is likewise formed if the temperature be kept low (150), but the isomeric para-hydroxy-benzoic acid at a higher temperature (220). Mono-potassic salicylate, C 6 H 4 (OH) C0 2 K, decomposes in an analogous manner at 220 into phenol and di-potassic ^-hydroxy-benzoate. As Kolbe's original method of preparation converted only 50 per cent of the phenol into salicylic acid, Schmitt devised the following modification: The sodic phenoxide is heated in a closed vessel with carbon dioxide at 130, and the compound first formed, C 6 H 5 '0C<^Q a , sodic phenyl-carbonate, is thus transformed into mono-sodic salicylate by the exchange of the CO ONa group with the ortho-hydrogen atom of the phenyl radical. (Cf. B.I 905, 38, 1375; A. 1907,351,313;C.C.1907,ii,48.) Salicylic acid crystallizes in colourless four-sided monoclinic prisms, dissolves sparingly in cold water but readily in hot; it melts at 155, can be sublimed, but is decomposed into phenol and C0 2 when heated quickly; ferric chloride colours the aqueous solution violet. It is an important antiseptic. It forms two series of salts (the basic calcium salt being insoluble in water), and two series of derivatives, viz.: (1) as an acid it yields chlorides, esters, &c., and (2) as a phenol it yields ethers, &c., e.g. ethyl-salicylic acid, C 6 H 4 (0 C 2 H 5 )C0 2 H. Phenyl salicylate, CWKco-OC ^ , the ester derived from phenol and salicylic acid, and generally termed "Salol", is a good antiseptic, and is prepared by the action of an acid chloride such as POC1 3 or COC1 2 upon a mixture of salicylic acid and phenol, or by heating the acid itself at 220. It forms colourless crystals. When its sodium salt is heated to 300, it undergoes molecular transformation into the sodium salt of the isomeric phenyl-salicylic acid, C 6 H 5 O.C 6 H 4 -C0 2 Na (B. 21, 501). Analogous "salols" are obtained from <;ther phenols, e.g. j?-acetylaminophenol yields salophene. m-Hydroxy-benzoic acid is prepared by diazotizing w-amino- benzoic acid. It crystallizes in microscopic plates, dissolves readily in hot water, and sublimes without decomposition; ferric chloride does not colour its aqueous solution. ^-Hydroxy-benzoic acid forms monoclinic prisms (-f- H 2 0), and ferric chloride gives no coloration with the aqueous solution. As a phenol it yields the methyl ether, anisic ttYDROXY-ACIDS 469 acid, C 6 H 4 (0 CH 3 ) C0 2 H, which can be prepared by treat- ing ^-hydroxy-benzoic acid with methyl alcohol, potash and methyl iodide, and saponifying the dimethyl derivative first formed; it is also formed by the oxidation of anisole. In consequence of the phenolic hydroxyl having been etherified, it resembles the monobasic and not the phenolic acids, boiling for example without decomposition; hydriodic and hydro- chloric acids at high temperatures decompose it into j?-hy- droxy-benzoic acid and methyl iodide or chloride. Hydro-para-coumaric acid (1 : 4), OH C 6 H 4 CH 2 CH 2 C0. 2 H, ^-p-hydroxy-plienyl-propionic add, is produced by the de lecay of tyrosine, fi-hydroxy-phenyl-alanine, OH C 6 H 4 CH 2 CH(NH 2 ) C0 2 H, and also synthetically from jo-nitro-cinnamic acid : NO 2 .C 6 H 4 .CH:CH.CO 2 H NH 2 .C 6 H 4 .CH 2 .CH 2 .CO 2 H reduced OH.C 6 H 4 .CH 2 .CH 2 .C0 2 H diazotized Tyrosine, which crystallizes in fine silky needles, is found in old cheese (TU/>OS), in the pancreatic gland, in diseased liver, in molasses, &c., and results from albumen, horn, &c., either upon boiling these with sulphuric acid or from their pancreatic digestion or their decay. It has also been obtained synthetically, as indicated by the following series of reactions: C 6 H 6 .CH 2 .CHO C 6 H 6 CH 2 CH(OH) . ON -f NH, C 6 H 6 .CH 2 .CH(NH 9 ).CN -* C 6 H 5 .CH 2 .CH(NH,)-CO 2 H NO 2 -C 6 H 4 .CH 2 .CH(NH 2 ).CO 2 H OH.C 6 H 4 .CH 2 .CH(NH 2 ).CO 2 H. (Compare also B. 32, 3638.) Of the numerous polyhydroxy-phenolic acids, the following may be mentioned : Protocatechuic acid, 3'A-Dihydroxy-benzoic acid, is obtained by fusing various resins, such as catechu, benzoin, and kino, with alkali. It may be prepared synthetically, together with the 2 : 3-dihydroxy-acid, by heating catechol, C 6 H 4 (OH) 2 , with ammonium carbonate. It crystallizes in glistening needles or plates, and is readily soluble in water; the solution is coloured green by ferric chloride, then after the addition of a very little sodic carbonate blue, and finally red. Like catechol it pos- sesses reducing properties. Its mono-methyl ether is vanillic 460 X!XVi. AltOMATiC ACtt)S acid, or p-hydroxy-nwnethoxy-benzoic acid, C 6 H 3 (C0 2 H)(0 CH 3 ) (OH), which is obtained by the oxidation of vanillin (p. 430); its dimethyl ether is the veratric acid of sabadilla seed (Ver- atrum Sabadilla), and its methylene ether is piperonylic acid, CH 2 <^Q^>C 6 H 3 C0 2 H, which can be prepared, among other methods, by the oxidation of piperic acid (p. 464). Gallic acid, 3 -A \5-Trihydroxy-benzoic acid, C 6 H 2 (OH) 3 C0 2 H, occurs in nut-galls, in tea and many other plants, and as gluco- sides in several tannins. It is prepared by boiling tannin with dilute acids, or by allowing mould to form on its solution, and has also been obtained synthetically by various reactions. It crystallizes in fine silky needles (+ H 2 0), dissolves readily in water, alcohol, and ether, and has a faintly acid and astringent taste. It evolves carbon dioxide readily when heated, yield- ing pyrogallol, reduces gold and silver salts, and yields a bluish-black precipitate with ferric chloride. Like pyrogallol, it is very readily oxidized in alkaline solution, with the pro- duction of a brown colour. Gallic acid is used in the manufacture of blue-black inks. With ferrous sulphate it gives a pale -brown colour, which rapidly turns black on exposure to the air; the presence of a minute quantity of free sulphuric acid retards this oxida- tion, but when the acidified solution is used with ordinary paper the acid is neutralized by compounds present in the paper, and the oxidation takes place. Indigo carmine is added to the ink in order to give it a blue colour before oxidation occurs. Dermatol and Airol are bismuth derivatives. Tannin, Gallotanic add, is a colourless, amorphous, glistening mass, readily soluble in water but only slightly in alcohol, and almost insoluble in ether. It forms the chief constituent of nut-galls, and is likewise present in sumach, tea, &c. It yields gallic acid when boiled with dilute acids, and a product similar to tannin may be obtained from gallic acid by the de- hydrating action of phosphorus oxychloride. The constitution is not known ; it is evidently a complex compound, and appears to be optically active. The aqueous solution is coloured dark-blue by ferric chloride. The mercury salt is used in medicine. Tannin has an affinity for the animal skin and for glue, and is abstracted from its solution by these substances, the skin being thus tanned or converted into leather. Numerous other tannic acids are known, and are usually named according to the plant from ALCOHOL-ACIDS 461 which they are obtained, e.g. kino tannin, catechu tannin, coffee tannin, &c. Quinic acid, which is found in quinine bark, coffee beans, &c., is a hexahydro-tetrahydroxy-benzoic acid, C 6 H 7 (OH) 4 C0 2 H. It crystallizes in colourless prisms and is optically active, an inactive modification being also known. 4. ALCOHOL- AND KETO-ACID3 The monobasic aromatic alcohol-acids, which possess at one and the same time the characters of acids and of true alcohols (p. 436), contain the alcoholic hydroxyl in the side chain; this hydroxyl is consequently eliminated together with the side chain when the compound is oxidized. In behaviour they approximate very closely to the hydroxy- acids of the fatty series, as the phenylated derivatives of which they thus appear; at the same time they yield, as phenyl de- rivatives, nitro-compounds, &c., although those compounds can often not be prepared directly, on account of the readiness with which the acids are oxidized. They differ from the phenolic acids in being more soluble in water, less stable, and non-volatile; as alcohols many of them give up water and yield unsaturated acids (which the phenolic acids can never do), and they can be esterified by hydrobromic acid, &c., with the formation of haloid-substitution acids, &c. Further, they are purely monobasic acids. The hydroxy-acids may be either primary, secondary, or tertiary alcohols, e.g. OH . CH 2 . C 6 H 4 . COOH, C 6 H 5 .CH(OH). COOH, and C 6 H 5 . CH 2 . C(CH 3 )(OH) . COOH. The tertiary can sometimes be prepared directly by the oxidation of such acids C n H 2n _ 8 2 as contain a tertiary hydrogen atom (:CH), by means of permanganate. To the ketonic acids the corresponding reactions apply. As ketones they may be reduced to secondary alcohol-acids, and they further react with hydroxylamine, &c.; as acids they form salts, esters, &c. Mandelic acid, Phenyl-glycollic acid, C<.H 5 . CH(OH) . C0 2 H (1835), is formed by hydrolysing amygdalin with hydrochloric acid, and synthetically by the hydrolysis of benzaldehyde-cyan- hydrin, C 6 H 5 . CH(OH) ON (see pp. 126 and 424). It forms glistening crystals, dissolves somewhat readily in water, and melts at 133. Mandelic acid possesses an asymmetric carbon atom and 462 XXVI. AROMATIC ACIDS exists in two optically active modifications (cf. B. 16, 1565 and 2721), and these can form a racemic compound (para-mandelic acid) in the same manner as d- and Z-tartaric acids. The acid obtained synthetically is the racemic acid, but this can be resolved (1) by the aid of chinchonine when the chin- chonine salt of the d-acid crystallizes first; (2) by means of green mould, " penicillium glaucum ", which when grown on a solution of the ammonium salt of the acid destroys the Isevo modification; (3) by partially esterifying the racemic acid with an optically active alcohol, e.g. Z-menthol; the non-esterified acid is then /-rotatory, as the d-acid is somewhat more readily esterified by /-menthol than the Z-acid. The method is not quantitative (Marckwald and Mackenzie, B. 1899, 32, 2130; 1901, 34, 469; also J. C. S. 1899, 964). The acid obtained from amygdalin is the laevo compound. It is comparable with lactic acid, CH 3 CH(OH) C0 2 H, yielding, like the latter, formic acid (together with benzoic) when oxidized; hydriodic acid reduces it to phenyl-acetic acid, just as it does lactic acid to propionic. o-Hydroxymethyl-benzoic acid, OH CH 2 CLH 4 CO OH, which is isomeric with mandelic acid, is unstable in the free state; as an ortho-compound, it readily yields the anhydride or lactone, Phthalide, C 6 H 4 <\QQ 2 ^>0, which is obtained by the reduction of phthalic anhydride or chloride. It crystallizes in needles or plates, and can be sublimed unaltered. Tropic acid, a- Phenyl-fi-hydroxy -propionic add, OHCH 2 CHPhC0 2 H (fine prisms), is obtained together with tropine by boiling atropine with baryta water; it is reconverted into atropine when warmed with tropine and hydrochloric acid. It exists in several optically different (d- t J-, and r-) modifi- cations. Benzoyl-formic acid, Phenyl-glyoxylic acid, C 6 H 5 COC0 2 H, is obtained synthetically by the hydrolysis of benzoyl cyanide, CgHg-CO-CN, with cold fuming HC1 (Claisen, 1877), and also by the cautious oxidation of mandelic acid or acetophenone. It is an oil which only solidifies slowly, and when distilled is largely decomposed into carbon monoxide and benzoic acid. It reacts similarly to isatin with benzene containing thiophene and sulphuric acid, and shows the normal reactions of the ketonic acids with NaHS0 3 , HCN, NH 2 -OH, &c. o-Nitro-benzoyl-fonnic acid, N0 2 C 6 H 4 .CO-C0 2 H, which can be prepared from 0-nitro-benzoyl cyanide, yields o amino- UNSATURATED PHENOLIC ACIDS 463 benzoyl-formic acid, isatic acid, NH 2 'C 6 H 4 CO-C0 2 H (a white powder), upon reduction; when a solution of the latter is warmed, it yields its intramolecular anhydride (lactam), isatin, > co < cf * Benzoyl-acetic acid, C 6 H 5 .CO-CH 2 .C0 2 H (JBaeyer), is a perfect analogue of acetoacetic acid, and, like the latter, can be used for the most various syntheses. It is obtained as its ethyl ester (which is soluble in cold sodic hydroxide solution) by dissolving ethyl phenyl-propiolate in concentrated sulphuric acid and pouring the solution into water (B. 16, 2128); or, better, by the action of sodium ethoxide upon a mixture of ethyl benzoate and acetate (Claisen's condensation, p. 225) (B. 20, 651). It is crystalline, melts at 103, and readily splits up into carbon dioxide and acetophenone, C 6 H 5 -CO'CH 3 ; the aqueous solution is coloured a beautiful violet by ferric chloride. 5. UNSATURATED MONOBASIC PHENOLIC ACIDS Hydroxy-cinnamic or Coumaric Acids, OHC 6 H 4 CH:CH COoH. The ortho-acid is present in melilot (Melilotus offidnalis), and can be prepared by diazotizing o-amino-cinnamic acid, or from salicylic aldehyde by Perkiris synthesis. The alcoholic solution is yellow with a green fluorescence. yO CO Coumarin, C 6 H 4 <^ , is the aromatic principle of wood- M-/H i CH ruff (Asperula odorata)^ and is also found in the Tonka bean and other plants. It is obtained by the elimination of water from 0-coumaric acid by means of acetic anhydride. It crys- tallizes in prisms, dissolves readily in alcohol, ether, and hot water; melts at 67, and boils at 290. It dissolves in sodium hydroxide solution, yielding the sodium salt of couniarinic acid. This salt is stereo-isomeric with that of 0-coumaric acid. The free acid itself appears to be incapable of existence, as it is immediately converted into coumarin (its anhydride), but various derivatives are known. o-Coumarinic acid is regarded as the cis-compound, as it yields an anhydride (cf. Maleic Acid). The stereo-isomeric o-coumaric acid is the trans-&c,id (cf. Fu- maric Acid): H-C.C 6 H 4 .OH H.C.C 6 H 4 .:OH H.OOC-C-H H c-co -6:H o-Couinaric Coumarinic acid, 464 XXVI. AROMATIC ACIDS 3 : 4-Dihydroxy-cinnamic acid, Cafeic add, (OH) 2 C 6 H 3 CH : CHCO 2 H, crystallizes in yellow prisms, and is obtained from caffetannic acid, whose mono-methyl ether is ferulic acid (from asafoetida); the isomeric umhellic acid or^?-hydroxy-0-coumaric acid readily changes into the anhydride corresponding to cou- marin, viz. umbelliferone, C 9 H 6 C 3 ; this last-named compound is present in varieties of Daphne. Related to the above is piperic acid: CH : CH CH : CH COaH, a decomposition product of piperine (p. 540), which crystallizes in long needles. B. Dibasic Acids The dibasic acids occupy exactly the same position in the aromatic series as the dibasic acids C n H 2n _ 2 4 do in the fatty. They contain two carboxyl groups; these may both be in the nucleus or in the side chain or chains, or be divided between them. They yield acid salts and normal salts, and similarly two series of esters, amides, &c. Dibasic phenolic acids can of course occur here also. 1. Phthalic acid, Benzene-o-dicarloxylic add, C 6 H 4 (C0 2 H) 2 (Laurent, 1836), is formed when any o-di-derivative of benzene, which contains two carbon side chains, is oxidized by HN0 3 or KMn0 4 , but not by Cr0 3 (cf. p. 438); it is generally formed by the oxidation of naphthalene by nitric acid, and also of anthra- cene derivatives. In preparing it on the large scale the naph- thalene is first converted into its tetra-chlor-addition product, CjpHgCl^ and then oxidized. At the present time phthalic acid is prepared on the commercial scale by oxidizing naph- thalene with concentrated sulphuric acid in the presence of a small amount of mercury or mercuric sulphate at 220-300. It crystallizes in short prisms or plates, melts at 213, and is readily soluble in water, alcohol, and ether. When heated above its melting-point, it yields the anhydride. When heated with lime, it yields benzoic acid or benzene according to the relative amounts of acid and lime used. Chromic acid dis- integrates it completely, while sodium amalgam converts it into dihydro-, tetrahydro-, and finally hexahydro-phthalic acid (see below). Its barium salt, C 6 H 4 (C0 2 ) 2 Ba, is sparingly soluble in water. K = 0-121. PHTHALIO ACIDS 465 Phthalic anhydride, C 6 H 4 <^pQ^>0, crystallizes in magnifi- cent long prisms which can be sublimed; it melts at 128, boils at 284, and is used in the preparation of eosin dyes (see Fluorescein). Phthalimide, C 6 H 4 <^QQ^>NH, corresponds with succinimide in many respects. It is obtained by passing dry ammonia over heated phthalic anhydride, and readily gives rise to metallic derivatives. The potassium salt C 6 H 4 (CO) 2 NK, obtained by the action of aqueous caustic potash on an alcoholic solution of the imide, readily reacts with alkyl iodides, yielding alkylated phthalimides, e.g. C 6 H 4 (CO) 2 NC 2 H 5 , and when these are hy- drolysed, primary amines, free from secondary and tertiary, are obtained, e.g. : C 6 H 4 :(CO) 2 :NC 2 H 5 + 2H 2 = C 6 H 4 (CO 2 H) 2 + C 2 H 6 NH 2 (Gabriel, B. 1887-1897). Numerous primary amines, including halogenated bases, which are difficult to prepare by other methods, have been obtained in this way. E. Fischer (B. 1901, 34, 455) has also used the same method for the preparation of the complex amine ornithine, NH 2 .CH 2 .CH 2 .CH 2 .CH(NH 2 ).C0 2 H, a5-diamino-?i- valeric acid. The various steps are: Potassium phthalimide and trimethylene bromide yield C 6 H 4 : (CO) 2 : N CH 2 CH 2 CH 2 Br, and this on condensation with ethyl sodio-malonate gives C 6 H 4 : (C0) 2 : N CH 2 CH 2 CH 2 CH(CO 2 Et) 2 ; and on bromination and subsequent hydrolysis and loss of carbon dioxide C 6 H 4 :(CO) 2 :N.CH 2 .CH 2 .CH 2 .CHBr.C0 2 H is obtained. Aqueous ammonia converts this into the corre- sponding amino-compound, and subsequent hydrolysis gives ornithine. The chloride, phthalyl chloride, which is obtained by the action of PCL upon the acid or the anhydride, appears not to C^C^~\ have the normal constitution C 6 H 4 (COC1) 2 , but C 6 H 4 as it yields phthalo-phenone, C 6 H 4 <>0, with benzene (B480) 2G 466 XXVI. AROMATIC ACIDS and aluminium chloride, and on reduction with sodium amal- PTT gam it yields phthalide, C 6 H 4 <^pQ 2 ^>0, the constitution of which is confirmed by its conversion on hydrolysis into 0-hy- droxy-methyl-benzoic acid (p. 462), OH . CH 2 . C 6 H 4 CO OH. 2. Isophthalic acid (1:3), prepared from m-xylene, crystal- lizes in slender needles from hot water, in which it is only sparingly soluble; it sublimes without forming an anhydride. The barium salt is readily soluble in water. K = 0'0287. Tlvitic acid is 5-methyl-isophthalic acid, and may be obtained by oxidizing mesitylene. 3. Terephthalic acid (1:4) is obtained by the oxidation of jp-xylene, cymene, &c., and especially of oil of turpentine or oil of cumin. It forms a powder almost insoluble in alcohol and water, and sublimes unchanged. For its preparation jp-toluic acid is oxidized by potassic permanganate (A. 258, 9). The barium salt is only sparingly soluble. A. Baeyer's researches (A. 245, 251, 258, 266, 269, and 276) have introduced us to a whole series of reduction products of phthalic acid, generally known as hydro-phthalic acids. The isomers among them differ from one another either by the position of the double bond in the ring (structural isomerism}, or by the spatial arrangement of the carboxyl groups with respect to the ring (stereo-isomerism). This latter isomerism corresponds to a certain extent with that of fumaric and maleic acids, but more closely with that of the poly-methylene compounds (p. 325), and a distinction is therefore made here also between a trans- and a as-form (cf. A. 245, 130). Exactly the same applies to the hydro-terephthalic acids. Of the hydro-phtlialic acids (A. 269, 147) there are now known : Five dihydro-acids (two of which are stereo-isomeric), four tetrahydro-acids (of which two again are stereo-isomeric), and two hexahydro-adds (which are stereo-isomers). Of the hydro-terephthalic acids (A. 258, 1), five dihydro-, three tetra- hydro-, and two hexahydro-acids are known, two in each group being stereo-isomeric. The following principles have largely served for determin- ing the position of the double bonds in these compounds: (1) When bromine substitutes in a carboxylic acid it takes up the a-position to the carboxyl (i.e. it is attached in the benzene nucleus to the same carbon atom to which the carboxyl is linked). (2) If two bromine atoms stand in the ortho-position to one another in a reduced benzene nucleus, they are elimi- HYDRO-PHTHALIC ACIDS 467 nated, without replacement, by the action of zinc dust and glacial acetic acid ; whereas, if they stand in the ^ra-positiori, they are replaced by hydrogen. (3) As in the case of the ali- phatic unsaturated acids, boiling with sodic hydroxide solution often gives rise to an isomeric acid, due to the " wandering " of a double bond in the direction of a carboxyl group (p. 162). (4) The stereo-isomeric modifications are also easily transformed one into the other. The relations existing between the five known dihydro- phthalic acids may be taken as an example. When phthalic acid is reduced by sodium amalgam in presence of acetic acid, tois-A-3 : 5-dihydro-phthalic acid is produced, and this changes into the ces-A-3 : 5-acid when heated with acetic anhydride : Both of these yield the A-2 : 6-dihydro-acid when warmed with alkali. When the dihydrobromide of the latter acid is treated with alcoholic potash, the A-2:4-dihydro-acid results, and, lastly, the anhydride of this yields the anhydride of the A-l : 4-dihydro- acid when heated: H H H A-2:6 A-2:4 A-l:4 All the dihydro-phthalic acids give anhydrides with the ex- ception of the tois-A-3 : 5-acid, which in this respect comports itself like fumaric acid. The following relationships have been established between the hydro-terephthalic acids: Terephthalic acid reduced with pure sodium amalgam in faintly alkaline solution gives a mixture of cis- and tois-A-2:5- dihydro-acids, both of which on oxidation readily yield tere- phthalic acid. When boiled with water both are converted into the A-l:5-dihydro-acid, and when boiled with caustic soda * In these formulae X = C0 2 H, A denotes the double bond, and the numbers refer to the carbon atoms after which the double bonds are placed. A-3:5 indicates two double bonds, one between carbons 3 and 4, and a second between carbons 5 and 6. 468 XXVI. AROMATIC ACIDS solution into the A-l : 4-dihydro-acid. This acid is the most stable of the dihydro-acids, and is always obtained by the reduction of terephthalic acid unless great care is taken in the reduction. When reduced with sodium amalgam the A-l:5-acid is con verted into a mixture of cis- and ^Yms-A-2-tetrahydro-acid. Both acids readily combine with bromine, which can again be removed by means of zinc dust; this dibromide, when warmed with alcoholic potash, gives the A-l:3-dihydro-acid, which cannot be obtained directly by the reduction of tere- phthalic acid. The A-1-tetrahydro-acid may be obtained by warming the A-2-acid with sodium hydroxide solution. The A-l -acid yields a mixture of two stereo-isomeric di- bromides (cis and trans), and these when reduced with zinc dust and acetic acid yield the cis- and /nws-hexahydro-tere- phthalic acid: X X X I X X II "I and I - ^ H A-l:5 Cis- and nms-A-2:5-dihydro XH X XH :H Hexahydro cis and trans Hi XH A-2-tetrahydro cis and trans A-l: 3- dihydro. The completely hydrogenized acids show great differences from the partially hydrogenized. Thus, hexahydro-terephthalic acid is exactly similar to a saturated acid of the fatty series; cold permanganate of potash has no effect upon it, while bro- mine substitutes (upon warming). On the other hand, the partially hydrogenized acids comport themselves precisely like the unsaturated acids of the fatty series with an open chain. They are very readily oxidized by cold permanganate, and take up bromine or hydrobromic HYDROXY-PHTHALIC ACIDS 469 acid until the saturation stage of the hexa-methylene ring is reached. All of the hydro-acids can be transformed back into phthalic acid (A. 1894, 280, 94). For hydro-ispphthalic acids, see W. H. Perkin, Jun., and S.S Pickles, P. 1905, 75, and Baeyer and Filliger, A. 1893, 276, 255. Two stereo-isomeric modifications of the hexahydro-acid are also obtained synthetically from derivatives of the fatty series (Perkin, J. C. S. 1891, 798). This constitutes a further proof that the hexahydro-benzene-carboxylic acids are nothing more than hexa-methylene derivatives. A large number of substitution products of the phthalic acids are known, e.g. chloro- and bromo-phthalic acids (which are used in the eosin industry), nitro-, amino-, hydroxy- and sulpho- phthalic acids, &c. HYDROXY-PHTHALIC ACIDS 2^5-Dihydroxy-terephthalic acid, quinol-p-dicarloxyUc actd, C 6 H 2 (OH) 2 (C0 2 H) 2 , in which both the hydroxyls and the car- boxy Is are respectively in the ^-position to one another, is obtained as its ethyl ester by the action of bromine upon succinylo-succinic ester, or of sodium ethoxide upon dibromo- acetoacetic ester. The free acid breaks up into quinol and carbon dioxide when distilled, and is converted by nascent hydrogen into succinylo-succinic acid. Succinylo-succinic acid, p-dihydroxy-dihydro-tereplithalic acid, C 6 H 4 (OH) 2 (C0 2 H) 2 , is obtained as its ethyl ester by the action of sodium upon ethyl succinate (see p. 342). The ethyl ester crystallizes in triclinic prisms which melt at 126, and dissolves in alcohol to a bright-blue fluorescent liquid which is coloured cherry-red by ferric chloride. It contains two replaceable hy- drogen atoms, being analogous to acetoacetic ester. The free acid, on losing carbon dioxide, changes into tetrahydro-quinone or p-diketo-hexamethylene. The ester may be represented as a dihydroxylic compound or as a diketone: C.C0 2 Et CH.C0 2 Et OH xx CO 2 Et ana reacts as a tautomeric substance (cf. Ethyl Acetoacetate). 470. XXVI. AROMATIC ACIDS C. Polybasie Acids Benzene s-tricarboxylic acid or trimesic acid, CJH 3 (COOH; 3 , can be obtained by the oxidation of mesitylene. The isomeric unsym. acid or trimellitic acid is obtained by the oxidation of colophonium, and the adjacent acid or heuiimellitic acid is obtained by oxidizing naphthalene-l:8-dicarboxylic acid. The benzene tetracarboxylic acids, C 6 H 2 (C0 2 H) 4 , prehnitic acid [1:2:3:4], mellophanic acid [1:2:3:5], and pyromellitic acid [1:2:4:5], are obtained by heating mellitic acid or its hexahydro-derivatives. Mellitic acid, Cg(CO 2 H) 6 , occurs in peat as aluminium salt or honey-stone, C 12 A1 2 12 + 18H 2 0, which crystallizes in octahedra, and is also formed by the oxidation of lignite or graphite with KMn0 4 . It forms fine silky needles of great stability, can neither be chlorinated, nitrated, nor sulphonated, but is readily reduced by sodium amalgam to hydromellitic acid, C 6 H 6 (C0 2 H) 6 , and yields benzene when distilled with lime. As regards the esterification of these polybasic acids, it has been found that carboxylic groups which have other carboxylic groups in two ortho-positions cannot be esterified by the usual catalytic process, e.g. on esterification by the Fischer -Speyer method, hemimellitic acid and prehnitic acid yield dimethyl esters only, pyromellitic acid yields a tetramethyl ester, and mellitic acid is not acted on (V. Meyer and Sudborouqh. B. 1894. 27, 3146). XXVII. AROMATIC COMPOUNDS CONTAIN- ING TWO OR MORE BENZENE NUCLEI. DIPHENYL GROUP The aromatic compounds hitherto considered, with the ex- ception of azobenzene, benzophenone, &c., contain but one benzene nucleus. In addition to these, however, a consider- able number of compounds are known which contain two or more such nuclei united in a variety of ways. Such com- pounds are usually arranged in the following groups: 1. Diphenyl group; this comprises the compounds with two benzene nuclei directly united together. The parent substance of the group is diphenyl, C 6 H 6 .C 6 H 6 . Dli>HENYL 471 2. Diphenyl-methane group; this includes all compounds with two benzene nuclei attached to a single carbon atom. The parent substance is diphenyl-methane, C 6 H 5 CH 2 C 6 H 5 . 3. Dibenzyl or stilbene group, which comprises compounds containing two benzene nuclei linked together by a chain of two or more carbon atoms, e.g. dibenzyl, C fi !L CH 2 CH 2 CJEL, and stilbene, C 6 H 5 . CH : CH . C 6 H 5 . 4. Triphenyl-methane group, which contains the compounds with three benzene nuclei attached to a single carbon atom, e.g. triphenyl-methane, CH(C 6 H 5 ) 3 . 5. In addition to the above groups several extremely im- portant groups are known which contain two or more benzene nuclei arranged in such a manner that they have two or more carbon atoms in common, e.g.: Naphthalene, ; anthracene, ; &c. These are usually termed compounds with condensed benzene nuclei. DIPHENYL GEOUP Diphenyl is related to benzene in much the same manner as ethane to methane: CH 4 and CH 3 - CH 3 C 6 H 6 and C 6 H 6 C 6 H 6 . Its molecule consists of two benzene nuclei directly united Its method of synthesis by Fittig, by the action of sodium on an ethereal solution of monoiodo-benzene or of copper-bronze at 230 (Ullmann, A. 332, 38), is analogous to the formation of ethane by the action of zinc or sodium on methyl iodide: 2C 6 H 6 I + 2Cu = C 6 H 6 .C 6 H 5 + Cu 2 I 2 . It is also formed by passing the vapour of benzene through a red-hot tube. It is contained in coal-tar, crystallizes in large colourless plates, melts at 71, boils at 254, and is readily soluble in alcohol and ether. Chromic acid oxidizes diphenyl to benzoic acid, one of the two benzene nuclei being destroyed, thus leaving only one carbon atom joined to the other benzene residue. From this and from its synthesis, the constitutional formula of diphenyl must be C 6 H 5 -C 6 H 6 . 472 XXVII. DIPHENYL GROUP Derivatives (Schulte, A. 207, 311). Like benzene, diphenyl is the mother substance of an extended series of derivatives which closely resemble the corresponding benzene derivatives in most respects. With polysubstituted derivatives the sub- stituents are usually denoted by the following numbers, accord- ing to the position occupied : Even the entrance of only one substituent produces isomers, since the latter may stand either in the 0-, m-, or ^-position to the point of union of the two benzene residues. The same applies in still greater degree to isomeric di-derivatives, of which o-o-, p-p-, o-p-, &c. compounds can exist. The consti- tution of these is elucidated from their syntheses, from their products of oxidation, or by conversion into compounds of known constitution; thus a chloro-diphenyl, C 12 H 9 C1, which yields ^>-chloro-benzoic acid when oxidized by chromic acid, is obviously ^-chloro-diphenyl. Whether all the substituents are attached to the one nucleus or are distributed between the two, can also be proved by an examination of the products of oxidation. The substituents take up the ^-position for choice; in di- derivatives the p-p- (and to a lesser extent the o-p-) position. Di-p-diamino- diphenyl, benzidine, NH 2 C 6 H 4 C 6 H 4 NH 2 (Zinin, 1845), is obtained by the reduction of ^-j9-dinitro- diphenyl (the direct nitration product of diphenyl); also, to- gether with diphenyline, by the action of acids upon hydrazo- benzene, the latter undergoing a molecular transformation (p. 395): C 6 H 6 .NH.NH.C 6 H 6 = NH 2 .C 6 H 4 .C 6 H 4 .NH 2 ; it is consequently formed directly from azobenzene by treating it with tin and hydrochloric acid. Benzidine is a diacid base which crystallizes in colourless silky plates, is readily soluble in hot water or alcohol, melts at 122, and can readily be sublimed. Its sulphate, C 12 H 10 (NH 2 ) 2 S0 4 H 2 , is sparingly soluble. Like its homo- logues (tolidine, &c.), it is of special importance in the colour industry, since, by coupling its diazonium-compound (tetra- zonium-diphenyl chloride) with naphthol-sulphonic or naph- thylamine-sulphonic acids, &c., colours are produced which CARBAZOLE. DIPHENYLENE OXIDE 473 dye unmordanted cotton directly, the so-called " substantive " or cotton dyes. To this class belongs the dye congo, (S0 3 Na)(NH 2 )C 10 H 6 N : N C 6 H 4 . C 6 H 4 . N : N C 10 H 6 (NH 2 )(S0 3 Na), prepared by means of naphthionic acid (p. 499), and the dye chrysamine G, prepared with salicylic acid. The isomeric diphenyline, 2 : 4'-diamino-diphenyl, may be obtained from 2 : 4'-dinitro-diphenyl, and also as a by-product in the preparation of benzidine from azobenzene. It crystal- lizes in needles, melting at 45, and yields a sulphate which is readily soluble. Carbazole, NH the imide of diphenyl, is contained in coal-tar and in crude anthracene. It is formed by distilling o-amino-diphenyl over lime at a low red heat, or by passing the vapour of diphenyl- amine through red-hot tubes, just as diphenyl is obtained from benzene: (C 6 H 6 ) 2 NH = (C 6 H 4 ) 2 NH + H 2 . It crystallizes in colourless plates sparingly soluble in cold alcohol, melts at 238, distils unchanged, and is characterized by the readiness with which it sublimes. Concentrated sul- phuric acid dissolves it to a yellow solution, and it forms an acetyl- and a nitro-compound, &c. The nitrogen in it occupies the di-ortho-position ; it thus appears, like indole, to be a pyr- role derivative, and it shows, in fact, most striking analogies to the latter (B. 21, 3299). Benzidine-mono-, di-, &c. sulphonic acids, e.g. C 12 H 6 (NH 2 ) 2 (S0 3 H) 2 , are of technical importance. The dihydroxy- diphenyls, C 12 H 8 (OH) 2 , of which four isomers are known, are formed (a) by diazotizing benzidine, (b) by fusing diphenyl- disulphonic acid with potash, and (c) by fusing phenol with potash or by oxidizing it with permanganate; in the last case hydrogen is separated and two benzene residues join together. p TT Diphenylene oxide, 6 4 /0, is obtained by distilling phenol C 6 H/ with plumbous oxide; it crystallizes in plates which distil with- out decomposition (cf. e.g. B. 25, 2745). The carboxylic acids of diphenyl are obtained (1) from the 474 XXVIII. DIPHENYL-METHANE GROUf corresponding nitriles, which on their part are prepared by distilling the sulphonic acids of diphenyl with KCN, e.g. di-p- diphenyl-dicarboxylic acid, C 12 H 8 (C0 2 H) 2 , a white powder insoluble in water, alcohol, and ether; (2) by the oxidation of phenanthrene and similar compounds, e.g., diphenic acid, C0 2 H-C 6 H 4 .C 6 H 4 .C0 2 H, the 2 : 2'-dicarboxylic acid, crystal- lizing in needles or plates which are readily soluble in the solvents just mentioned; rn.-pt. 229. Both of these are di- basic acids, which yield diphenyl when heated with soda-lime. The homologues of diphenyl are, like the latter, obtained by means of Fittig's reaction. Analogous to benzidine is 0-tolidine, Ci 2 H 6 (CH 3 ) 2 (NH 2 ) 2 , m.-pt. 128, whose diazo-compound unites with naphthionic acid to the red substantive dye, benzo-pur- purine 4B. Similarly di-anisidine or dimethoxy-benzidine, C 12 H 6 (0 CH 3 ) 2 (NH 2 ) 2 , yields diazonium salts which combine with a-naphthol-a-sulphonic acid to form a blue substantive dye, benzazurine G. Diphenyl may be regarded as monophenyl -benzene; the corresponding di- and triphenyl-benzenes are also known. ^-Diphenyl-benzene, C C H 4 (C 6 H 5 ) 2 , may be obtained by the action of sodium upon a mixture of ^-dibromo-benzene and bromo-benzene. It crystallizes in flat prisms, melts at 205, and on oxidation yields diphenyl-monocarboxylic and tere- phthalic acids. When hydrochloric acid gas is led into acetophenone, C 6 H 5 CO CH 3 , a reaction analogous to the formation of mesitylene from acetone (p. 342) ensues, and s-triphenyl-benzene, C 6 H 3 (C 6 H 5 ) 3 (rhombic plates), is formed. XXVIII. DIPHENYL-METHANE GROUP Diphenyl-methane, C 6 H 5 CH 2 C 6 H 5 , is derived from methane by the replacement of two hydrogen atoms by two phenyl groups, and is thus closely related to phenyl-methane or toluene, C 6 H 5 CH 3 . One important difference is that when oxidized it cannot yield an acid containing the same number of carbon atoms since it does not contain a methyl group. It can be oxidized to the secondary alcohol benzhydrol, (C 6 H 5 ) 2 CHOH, or the ketone benzophenone, (C 6 H 5 ) 2 CO. Compounds like diphenyl-ethane, (C 6 H 5 ) 2 CH CH 3 , can yield acids. The various derivatives are obtained by substituting one DIPHENYL-METHANE 475 or more of the twelve hydrogen atoms present in the diphenyl- methane molecule. If the substituent replaces any of the ten hydrogens directly attached to the benzene nuclei, a com- pound is formed which closely resembles the corresponding derivatives of benzene, e.g. C 6 H 5 CH 2 C 6 H 4 NH 2 closely re- sembles aniline. If, on the other hand, the substituent replaces a hydrogen atom of the methylene group, a compound with aliphatic properties is obtained, e.g. (C 6 H 5 ) 2 CHOH closely resembles a secondary aliphatic alcohol. The method of numbering the carbon atoms in the diphenyl- methane molecule is usually as follows : Formation of diphenyl-methane and its derivatives. 1. Diphenyl-methane is produced by the action of benzyl chloride upon benzene, in presence of zinc dust (Zincke, A. 159, 374), or of aluminium chloride (Friedel and Crafts): = C 6 H 6 .CH 2 .C 6 H 5 + The homologues of benzene, and also the phenols and tertiary amines, may be used instead of benzene itself. In an exactly analogous manner diphenyl-methane is ob- tained by the action of methylene chloride, CH 2 C1 2 , upon benzene in presence of aluminium chloride: CH 2 C1 2 + 2C 6 H 6 = CH 2 (C 6 H 6 ) 2 2. Diphenyl-methane hydrocarbons are formed by the action of the aliphatic aldehydes, e.g. acetaldehyde or formaldehyde, upon benzene, &c., in the presence of concentrated sulphuric acid (Baeyer, B. 6, 963). With formaldehyde diphenyl-methane, or with acetaldehyde diphenyl-ethane, is formed: CH 3 .CHO + 2C 6 H 6 = CH 3 .CH(C 6 H 6 ) 2 + The acetaldehyde and formaldehyde are employed here in the form of paraldehyde and methylal. Formaldehyde itself condenses with aniline to diamino-, and with dimethyl-aniline to tetramethyl- diamino -diphenyl-methane. When aromatic aldehydes are used, triphenyl-methane derivatives are formed (p. 480). 3. Aromatic alcohols react with benzene and sulphuric acid in an analogous manner (V. Meyer): C 6 H 6 .CH 2 -OH 476 XXVIII. DIPHENYL-METHANB GROUP Similar reactions have also been brought about by means of ketones, aldehydo-acids, and keto-acids on the one hand, and phenol and dialkylated anilines on the other. The true aromatic ketones of the type of benzophenone may be regarded as diphenyl-methane derivatives (see p. 428). Diphenyl-methane, (CgH 5 ) 2 CH 2 , is most conveniently pre- pared from benzyl chloride, benzene, and aluminic chloride. It crystallizes in colourless needles of very low melting-point (26), is readily soluble in alcohol and ether, has a pleasant odour of oranges, and distils unaltered at 262. It yields nitro-, amino-, and hydroxy-derivatives. ^-Diamino- diphenyl-methane, CH 2 (C 6 H 4 NHA2, is obtained by heating anhydro-formaldehyde-aniline, C 6 Hg N : CH 2 , prepared from formaldehyde and aniline, with aniline and an aniline salt. It crystallizes in lustrous silvery plates, melting at 87*, and may be used for the preparation of fuchsine. Bromine at a moderate temperature reacts with the hydrocarbon yielding diphenyl-bromo- methane, (C 6 H 5 )oCHBr, and when this is heated with water to 150, it yields benzhydrol, diphenyl-car- binol, (C 6 H 6 ) 2 CHOH, which can also be obtained from benzo- phenone and sodium amalgam, or by Grignard's synthesis. It crystallizes in glistening silky needles, melts at 68, possesses in every respect the character of a secondary alcohol (forming esters, amines, &c.), and is readily oxidized to the correspond- ing ketone, benzophenone, (C 6 IL) 2 CO (p. 428). aa-Diphenyl-ethane, (C 6 H 5 ) 2 CH GEL (isomeric with dibenzyl, see p. 477), is obtained by method of formation 2 (p. 475). It is a liquid, boils at 286, and is oxidized to benzophenone by chromic acid. From it is derived : Benzilic acid, diphenyl-gly collie add, (C 6 H 5 ) 2 C(OH) C0 2 H, which is formed by a molecular transformation when benzil, C 6 H 5 .CO.CO-C 6 H 5 (p. 479), is fused with potash. It crystal- lizes in needles or prisms, dissolves in concentrated sulphuric acid to a blood-red solution, and is reduced by hydriodic acid to diphenyl-acetic acid, (C 6 H 6 ) 2 CH C0 2 H (needles or plates), which may also be obtained synthetically from phenyl-brom- acetic acid, C 6 ILCHBr 'GOgH, benzene, and zinc dust, accord- ing to mode of formation 1, p. 475. Tolyl-phenyl-methanes, C 8 H 5 CH 2 C 6 H 4 CH 3 . The p- and o- compounds are obtained from benzyl chloride and toluene. Benzoyl-benzoic acids, benzophenone-carboxylic acids, C 6 H 5 CO.C 6 H 4 .C0 2 H (B. 6, 907). Of these the o-acid (m.-pt. 127) has been prepared synthetically by heating phthalic anhydride DIBENZYL GROUP 477 with benzene and aluminic chloride. When heated with phosphorus pentoxide at 180, it yields anthra-quinone, H various transformations into the anthra- cene series have been effected in a similar manner from o-tolyl- phenyl-methane and the corresponding ketone. C 6 H 4 \ Fluorene, diphenylene-methane, /CH 2 , stands in the CgH/ same relation to diphenyl-methane as carbazole (p. 473) does to diphenylamine; it is at the same time a diphenyl and a methane derivative. It is contained in coal-tar, and is pro- duced when diphenyl-methane is led through red-hot tubes (like diphenyl from benzene), and also by passing the vapour of diphenylene-ketone over red-hot zinc dust. It crystallizes in colourless plates with a violet fluorescence, melts at 113, and boils at 295. The corresponding ketone, diphenylene- ketone, C 12 H 8 :CO, which crystallizes in yellow prisms melting at 84, is obtained by heating phenanthra-quinone with lime, and is converted into fluorenyl alcohol, (C 6 H 4 ) 2 : CH OH (colourless plates, m.-pt. 153), by nascent hydrogen, and into diphenyl-carboxylic acid, o-phenyl-benzoic acid, C 6 C0 2 H, by fusion with potash. XXIX. DIBENZYL GROUP This group comprises the compounds containing two ben- zene nuclei connected by a chain of two carbon atoms. Among the most important members are: Dibenzyl, C 6 H 5 .CH 2 .CH 2 .C 6 H 5 ; stilbene, C 6 H 5 .CH:CH.C 6 H 5 ; tolane, C 6 H 5 C : C C 6 EU; deoxybenzoin, C 6 H 5 CH 2 CO C 6 H 5 , hydrobenzoin, C 6 H 5 CH(OH) CH(OH) C 6 H 5 ; benzoin, C 6 H ff .CH(OH).CO.C 6 H,; benzil, C 6 H 5 .CO.CO.C 6 H 5 . Dibenzyl is symmetrical diphenyl-ethane (for the unsym- metrical compound, see p. 476), stilbene is s-diphenyl-ethylene, and tolane diphenyl-acetylene. All these compounds yield benzoic acid when oxidized. Dibenzyl is formed when benzyl chloride is treated with metallic sodium, or by the action of benzyl chloride on benzyl magnesium chloride. It is often met with as a by-product in Grignard's synthesis by means of benzyl magnesium chloride. 478 XXIX. DIBENZYL GROUP It is isoineric with ditolyl and with tolyl-plienyl-methane ; it crystallizes in needles or small plates, melts at 52, and sublimes unchanged. Stilbene, s-diphenyl-ethylene, forms monoclinic plates or prisms, melts at 125, and also boils without decomposition. It may be prepared by the action of sodium upon benzal chloride, or by heating deoxybenzoin with sodium ethoxide, or best by the action of benzyl magnesium chloride on benzaldehyde, and possesses the full character of an olefine, giving, for instance, a dibromide, C 6 H 5 CHBr CHBr C 6 H 5 , with bro- mine, and being converted into dibenzyl by hydriodic acid. ^-Diamino- stilbene, C 14 H 10 (NH 2 ) 2 , and its disulphonic acid (obtained by reducing ^-nitro-toluene or its sulphonic acid in alkaline solution) are, like benzidine, mother substances of "substantive dyes" (see p. 473). Stilbene should exist in two stereo-isomeric modifications, the ordinary stilbene melting at H .C-Ph 125 is usually regarded as the trans compound Ph C H An isomeride the cis compound has been described by Otto and Sto/el (B. 1897, 30, 1799). Just as ethylene bromide yields acetylene when boiled with alcoholic potash, so stilbene dibromide yields tolane, which crystallizes in prisms or plates, melting at 60. It may also be prepared by the following series of reactions: C 6 H 6 .CH 2 .CO.C 6 H 6 C 6 H 5 .CH:CC1.C 6 H 6 C 6 H 6 .C:C.C 6 H 6 . Phosphorus pentachloride Alcoholic potash Tolane corresponds with acetylene in its properties in so far that it combines with chlorine to a dichloride and a tetra- chloride; but it does not yield metallic derivatives, since it contains no "acetylene hydrogen" (p. 51). When stilbene dibromide is treated with silver acetate, two di-acetates are formed; and when these are hydrolysed by alcoholic ammonia, two isoineric substances of the composition, C 6 H 5 .CH(OH).CH(OH).C 6 H 5 , hydrobenzoin and iso-hydro- benzoin or s-diphenyl-glycol, are produced. Both compounds are also formed by the action of sodium amalgam upon oil of bitter almonds. The former crystallizes in rhombic plates, melting at 138, and the latter in four-sided prisms, melting at 119, and is the more soluble of the two. The two com- pounds are stereo-isomeric in the same manner as meso-tartaric and racemic acid, and JSrlenmeyer, Junr., has been able to re- solve hydrobenzoin, which corresponds Mith racemic acid, into BENZIL. DEOXYBENZOIN 479 two optically active components, by separating two different kinds of hemihedral crystals (A. 198, 115, 191; B. 30, 1531). The compounds benzoin, benzil, and deoxy benzoin, which have already been mentioned, are closely related to one an- other, as their formulae show, and can also be prepared from benzaldehyde. When the aldehyde is boiled with an alcoholic solution of potassium cyanide it polymerises,* yielding benzoin, 2C 6 H 6 .CH:0 = C 6 H 6 .CH(OH).CO.C 6 H 6 , which forms beautiful glistening prisms, m.-pt. 134; nascent hydrogen reduces it to hydrobenzoin, from which it can also be obtained by oxidation. It reduces Fehling's solution even at the ordinary temperature, yielding benzil. Benzil, C 6 H 5 CO CO C 6 H 5 , is obtained by oxidizing ben- zoin with nitric acid. It crystallizes in large six-sided prisms, melting at 95. It is oxidized to benzoic acid by chromic anhydride, and reduced by nascent hydrogen according to the conditions either to benzoin or to deoxybenzoin. It reacts with hydroxylamine to produce: Benzil-monoxime, C 6 H .CO^C(:N.OH).C 6 H 5 , and benzil- dioxime, C 6 H 5 .C(:N.OH).C(:N.OH).C6H 5 , which exist in the following sfeereo-isomeric modifications (Hantzsch and Werner, B. 23, 11; 37, 4295; Dittrich, ibid., 24, 3267): Monoximes : C 6 H 6 .C.CO-C 6 H 6 C 6 H 6 .C.CO.C 6 H 6 N-OH Heated HO-N eu M.-pt. 134* y. M.-pt. 113*. Dioximes : C 6 H 5 .C C.C 6 H 5 _^ C 6 H 6 .C C.C 6 H 5 ^_ C 6 H 5 .C C.C 6 H 6 N-OH HO-N " HO-N N-OH " " HO-N HO-N ou M.-pt. 237 j3. M.-pt. 207 y. M.-pt. 163. The configurations have been established as the result of an examination of the products obtained by the Beckmann trans- formation (A. 296, 279; 274, 1. Compare pp. 139 and 429). Deoxybenzoin, C 6 H 5 CH 2 CO C 6 H 5 , forms large plates, melting at 55, and may be sublimed or distilled unchanged. It can be prepared by the action of benzene and aluminium chloride upon phenyl-acetyl chloride, C 6 H 5 CHg CO Cl, and hence its constitution, and yields di-benzyl with hydriodic acid. Deoxybenzoin can also be prepared from benzil and benzoin (B. 25, 1728). One of its methylene hydrogen atoms * For mechanism, cf. Chalanay and Knoevenayd (B. 1892, 25, 295). 480 XXX. TRIPHENYL-METHANE GROUI is re t adilv replaceable by alkyl, just as in acetoacetic ester. The radical, CH(C 6 H 5 ) . CO C 6 H 5 , is termed "desyl". Benzilic acid, (C 6 H 5 ) 2 C(OH) C0 2 H (p. 476), is produced when benzil is heated with alcoholic potash, by a peculiar molecular transformation similar to that by which pinacoline is formed (p. 193). Compounds closely related to the dibenzyl group are those which contain two benzene nuclei united by a chain of more than two carbon atoms, e.g. ay-dipbenyl propane, and also those compounds containing three or more benzene nuclei united by a chain of carbon atoms, e.g. triphenyl-ethane, tetra- phenyl-ethane, &c. XXX. TRIPHENYL-METHANE GROUP Triphenyl-methane, CH(C 6 H 5 ) 3 , is the compound obtained as the result of the entrance of three phenyl groups into the methane molecule; among its homologues are tolyl-diphenyl- methane, (C 6 H.) 2 CH - C 6 H 4 CH, ditolyl - phenyl - methane, C 6 H 5 .CH(0 6 H 4 .CH S ).,, &c. These hydrocarbons are of especial interest as being the mother substances of an extensive series of dyes; the amino-, hydroxy-, and carboxy-derivatives of triphenyl- methane are the leuco-bases obtained from such dyes as rosaniline, aurine, malachite green, &c. Their formation is effected in a manner analogous to that of the diphenyl-methane derivatives, i.e. by the aid of zinc dust or aluminic chloride when chlorine compounds are used, or by the aid of phosphoric anhydride when oxygen compounds are employed. Thus, triphenyl-methane may be obtained (a) from benzal chloride and benzene in the presence of aluminic chloride, C 6 H 6 .CHC1 2 + 2C 6 H 6 = CH(C 6 H 6 ) 3 + or from benzaldehyde, benzene, and zinc chloride; (b) from chloroform and benzene in presence of aluminic chloride, 3C 6 H 6 + CHC1 3 = CH(C 6 H 6 ) 3 + 3HC1; (c) from benzhydrol and benzene in the presence of phos- phoric anhydride, (C 6 H 6 ) 2 CH.OH-f C 6 H 6 = (C 6 H 6 ) 2 CH.(C 6 H 6 ) + H a O. I'RIPHENYL-METHANE 481 Derivatives of triphenyl - methane may be obtained by similar methods, e.g. the leuco-base of bitter-almond-oil green, tetramethyl-diamino-triphenyl-methane (cf. p. 483), may be prepared by the condensation of benzaldehyde and dimethyl- aniline : C 6 H 6 .CHO + 2C 6 H 6 .N(CH3) 2 = C 6 H 6 .CH:[C 6 H 4 .N(CH s ) 2 ] 2 -f H 2 O. When other amines or even phenols are used, a series of allied compounds (which are often dyes) is obtained, the sepa- ration of water being facilitated by the addition of zinc chlo- ride, concentrated sulphuric acid, or anhydrous oxalic acid. Triphenyl -methane, CH(C 6 H 5 ) 3 (KekuU and Franchimont, B. 5, 906). This compound may be prepared from chloroform and benzene by the Friedel-Cmfts reaction (cf. A. 194, 152), diphenyl-methane being produced at the same time; also by eliminating the amino-groups from ^-leucaniline, C 19 H 13 (NH 2 ) 3 , and most readily by reducing triphenyl-carbinol with zinc dust and acetic acid. It crystallizes in colourless prisms, m.-pt. 93, b.-pt. 359, and dissolves readily in hot alcohol, ether, and benzene. It crystallizes from benzene with one molecule of " benzene of crystallization", which is also the case with many triphenyl- methane derivatives. When triphenyl-methane is treated with bromine in a solution of carbon bisulphide, the methane hy- drogen atom is exchanged for bromine with the formation of triphenyl-methyl bromide, (C 6 H 5 ) 3 -CBr, which, when boiled with water, yields triphenyl-carbinol, (C 6 H 5 ) 3 C-OH. This crystallizes in glistening prisms, melts at 159, and can be sublimed unchanged; it may also be prepared directly by oxidizing a solution of triphenyl-methane in glacial acetic acid with chromic acid, or synthetically by the action of Grignard's phenyl magnesium bromide on benzophenone or ethyl benzoate : (C 6 H 6 ) 2 CO (C 6 H 6 ) 3 C.OMgBr (C 6 H 6 ) 3 C.OH. A number of homologues of triphenyl-methane have been- prepared by this last method (Houben, B. 1903, 36, 3087). Fuming nitric acid converts triphenyl-methane into trinitro- triphenyl-methane, (C 6 H 4 N0 2 ) 3 *CH (yellow scales), which can then be oxidized by chromic acid to trinitro-triphenyl- carbinol, (C 6 H 4 N0 2 ) 3 C OH. The latter gives para-rosaniline, (C 6 H 4 NH 2 ) 3 C OH, when reduced with zinc dust and glacial acetic acid. Homologous with triphenyl-methane are the tolyl-diphenyl- (B480) 2H 482 XXX. TRIPHENYL-METHANE GROUP methanes, (C 6 H 5 ) 2 CH'C 6 H 4 CH 3 . From these also dyes are derived, especially from m-tolyl-diphenyl-methane (in which the CH 3 occupies the meta-position with regard to the methane carbon atom), which can be prepared by diazotizing ordinary leucaniline; it crystallizes in small prisms and melts at 59 -5 TRIPHENYL-METHANE DYES Of the derivatives of triphenyl-me thane and of tolyl-di- phenyl-methane, those are especially interesting which contain amino-, hydroxy-, or carboxy-groups. The entrance of three amino- or hydroxy-groups converts them into the leuco-com- pounds of dyes, some of which latter are of great value. Two amino -groups suffice for the full development of the dye character only when the amino-hydrogen atoms are replaced by alkyl radicals, one amino-group being insufficient for this (see under ^-amino-triphenyl-methane). The following are the chief groups of triphenyl-methane dyes: 1. Those derived from diamino- triphenyl-methane. The malachite-green group. 2. Those derived from triamino- triphenyl-methane. The rosaniline group. 3. Those derived from trihydroxy-triphenyl-methane. The aurine group. 4. Those derived from triphenyl-methane-carboxylic acid. The eosin group. Leuco-bases or leuco-compounds of dyes (p. 399) are the colourless compounds formed by the reduction of the dyes, usually by the addition of two atoms of hydrogen. When oxidized they are converted back into the dyes. All the dyes of the triphenyl-methane group, and also indigo, methylene blue, safranine, &c., are capable of yielding such leuco-compounds, generally on reduction with zinc and hydrochloric acid, stannous chloride, or ammonium sulphide. The oxidation of the leuco-compounds is often quickly effected by the oxygen of the air (e.g. in the cases of indigo white and of leuco-methylene blue) ; in the triphenyl-methane group it is slower and frequently more complicated Leuco- malachite green is readily oxidized to the corresponding colour-base when treated with lead peroxide in acid solution, and leucaniline when warmed with chloranil in alcoholic solution, or when its hydrochloride is heated either alone or AMINO- AND DIAMINO-TRIPHENYL-METHANE DYES 483 with a concentrated solution of arsenic acM, or with metallic hydroxides such as ferric hydroxide. The leuco-bases of the triphenyl-methane dyes are deriva- tives of triphenyl-methane or its homologues, the corresponding dye-bases obtained by oxidizing the leuco-bases are derivatives of triphenyl-carbinol or its homologues, and the dyes them- selves are salts obtained by the elimination of water from the dye-base and an acid. The relationships between the three groups of compounds leuco-base, dye-base, and dyes are in- dicated in the following scheme: oxidized acid Leuco-base ^ dye-base ^ dye. reduced alkali As an example: CH(C H 4 .N H2 ) 3 - O ' U T J^^ 1 -H 2 1. AMINO- AND DIAMINO- TRIPHENYL-METHANE GROUP ^-Amino-triphenyl-methane can be synthesized either by the condensation of jp-nitro-benzaldehyde with benzene and subsequent reduction, or from benzhydrol and aniline. It forms large prisms, and melts at 84. The corresponding car- .binol is colourless and with acids yields red salts, but these cannot dye animal fibres. ^-Diamino- triphenyl-methane, C 6 H 5 CH(C 6 H 4 NH 2 ) 2 , is prepared by the action of zinc chloride or of fuming hydro- chloric acid upon a mixture of benzaldehyde and aniline sulphate or chloride: = C 6 H fi .CH(C 6 H 4 .NH 2 ) 2 + H 2 O. It crystallizes in prisms, and the colourless salts yield an unstable blue-violet dye, benzal violet, when oxidized. Me- thylation converts the base into: Tetramethyl - di-p-amino - triphenyl - methane, leuco-malachite green, C 6 H 5 CH[C 6 H 4 -N(CH 3 ) 2 ] 2 , which is prepared on the technical scale by heating benzaldehyde and dimethyl-aniline with zinc chloride or concentrated sulphuric acid (0. Fischer, A. 206, 103). It forms colourless plates or prisms. As a diacid base it yields colourless salts, which are slowly converted by the air, but immediately by other oxidizing agents, such as lead dioxide and sulphuric acid, into the salts of tetramethyl- Oiamino - triphenyl - carbinol, C e tI 5 C (OH) [C 6 EyST(CH 3 ) 2 ] 2 . 484 XXX. TRIPHENYL-METHANE GROUP The free base is obtained by precipitating the salts with alkali. It crystallizes in colourless needles and dissolves in cold acid to a colourless solution; upon warming, however, the intense green coloration of the salts is produced. (For an explana- tion of this, see p. 486.) The double salt with zinc chloride, ((X 3 H 25 N 2 C1) 3 , 2ZnCl 2 , 2 H 2 O, or the oxalate, (C 23 H 25 N 2 ) 2 , 3 H 2 C 2 O 4 , of this base is the valuable dye bitter-almond-oil green, malachite green or Victoria green, which forms green plates, readily soluble in water. This can also be prepared directly by heating benzo-trichloride with dimethyl-aniline and zinc chloride (Doebner). Brilliant green is the corresponding tetraethyl compound. The sulphonic acid of the diethyl-dibenzyl-diamino-triphenyl- carbinol is acid green. 2. ROSANILINE GROUP Fuchsine or magenta was first obtained in 1856 by Natanson, who noticed the formation of a red substance, in addition to that of aniline hydrochloride and ethylene-aniline, when ethy- lene chloride was allowed to act upon aniline at a temperature of 200 (A. 98, 297). It was prepared shortly afterwards by A. W. Hofmann, by the action of carbon tetrachloride upon aniline, and was first manufactured on the technical scale in 1859. Hof- mann's scientific researches on this subject date from 1861. The chemical constitution was made clear by Emit and Otto Fischer in 1878 (A. 194, 242). (Of. also Caro and Grabs, B. 11, 1116.) The rosaniline dyes are derived partly from triphenyl- methane and partly from wi-tolyl-diphenyl-methane; in the former case they are often designated para-compounds (e.g. "para-rosaniline", because it is prepared from aniline and para- toluidine ; " para-rosolic acid "). Para-leucaniline, triamino-triphenyl-methane, CH(CLH 4 'NH 2 ) 3 , andleucaniline, triamino-diplienyl-tolyl-'methane, CH 3 C 6 H 3 (NH 2 ) CH(CgH 4 NH 2 ) 2 , are formed by the reduction of the corre- sponding trinitro- compounds and also of the corresponding dye-bases, para-rosaniline and rosaniline; the first named like- wise by the reduction of ^-nitro-diamino-triphenyl-methane. The free leuco-bases are precipitated by ammonia from solutions of their salts as white or reddish flocculent masses, and crystal- lize in colourless needles or plates; they melt at 203 and 100 respectively. As triacid bases they form colourless crystalline salts. PARA-ROSANILINE AND ROSANILINE 485 Para-rosaniline, OH C(C 6 H 4 NH 2 ) 3 , and rosaniline, OH- N xr 2 R are the bases of the fuchsine dyes. They IN -0-2 are obtained by precipitating solutions of their salts with alkalis, and crystallize from hot water or alcohol in colourless needles or plates, which become red in the air. Both are tri- acid bases, stronger than ammonia. As they yield tri-diazonium salts on treatment with nitrous acid, they must contain three primary amino- groups. The diazonium compounds readily yield the corresponding hydroxylic dyes, aurine and rosolic acid (p. 490), when boiled with water. Constitution. The relations between the rosanilines and tri- phenyl-methane were made clear by Emil and Otto Fischer, who transformed leucaniline into diphenyl-tolyl-methane by diazo- tizing and decomposing with alcohol. In a similar manner, para-leucaniline was converted into triphenyl-methane. The two leuco-bases are, therefore, undoubtedly triamino-derivatives of diphenyl-^-tolyl-methane and of triphenyl-methane respec- tively. The dye-bases, which differ from the leuco-bases by one atom of oxygen, are the corresponding carbinol derivatives, i.e. rosaniline is triamino-diphenyl-^-tolyl-carbinol, and para- rosaniline triamino-triphenyl-carbinol. That the three amino-groups are distributed equally among the three benzene nuclei is clear from the synthesis of para- leucaniline by means of ^-nitro-benzaldehyde. ^?-Nitro-ben- zaldehyde, aniline, and sulphuric acid yield ^-nitro-diamino- triphenyl-methane, N0 2 C 6 H 4 CH(C 6 H 4 NH 2 ) 2 , which, when reduced, yields para-leucaniline. We have, therefore, the following formulas : 5 H 4 .NH 2 yC 6 H 4 .NH 2 8 H 4 .NH 2 C(OH)^C 6 H 4 .NH 2 8 H 4 NH 2 \C 6 H 3 (CH 3 ) NH 2 Para-leucaniline. Rosaniline. It can be shown that each amino -group occupies the p- position with respect to the methane carbon atom. Diamino- triphenyl-methane can be synthesized from benzaldehyde and aniline in the presence of a dehydrating agent. When diazotized and warmed with water, the corresponding dihy- droxy-triphenyl-methane is formed, and this, when fused with potash, yields ^-dihydroxy-benzophenone : C 6 H 6 .CH(C 6 H 4 NH 2 ) 2 C 6 H 6 .CH(C 6 H 4 .OH) 2 CO(C 6 H 4 .OH) 2 in this last compound the ^-positions of the hydroxy-groupa 486 XXX. TRIPHENYL-METHANE GROU? have been established, and hence the original ammo-groups must also have occupied the p-positions, unless intramolecular rearrangement has occurred. When^-nitro-benzaldehyde is condensed with aniline, ^-nitro- diamino-triphenyl-methane is formed, and the nitro-group must be in the ^-position, and by analogy with the previous reaction the two amino-groups are also in ^-positions, and as this com- pound on reduction yields para-leucaniline it follows that all three amino-groups occupy ^-positions a conclusion which is supported by the fact that para-leucaniline can also be trans- formed into jp-dihydroxy-benzophenone. The salts of rosaniline and para - rosaniline, fuchsine, C 20 H 20 N 3 C1, rosaniline nitrate, C 20 H 20 N 3 (N0 3 ), rosaniline acetate, C 20 H 2? N 3 (C 2 H 3 2 ), para-fuchsine, C 19 H 18 N 3 C1, &c., are the actual dyes. While they possess a magnificent fuchsine-red colour in solution, and have intense colouring power (dyeing wool and silk without a mordant), their crys- tals are of a brilliant metallic green with cantharides lustre, i.e. of nearly the complementary colour. They are fairly soluble in hot water and alcohol. In the formation of the salts, water is eliminated: qOH)(C 6 H 4 .NH 2 ) 3 + HCl = C 19 H 17 N 3 , HC1 + H 2 0. In the dyes there is therefore present a peculiar nitrogen- carbon linking (see formula I), which is reminiscent of the older quinone formula; but the simpler constitution (formula II), which corresponds with the newer quinone formula, is now more generally accepted, and is usually termed the quinonoid formula : (I) (II) C(C 6 H 4 NH 2 ) 2 NH 2 /C 6 H 4 -NH 2 } H 4 .NH 2 C-C,H -NH 2 4 .NH,HC1 XVH 4 :NH,HC1 or (Fischer) (Nietzki) f<. Para-rosaniline chloride. NH 2 C1 An analogous separation of water is also observed in the formation of salts of the malachite green base, but this only takes place upon warming, as is proved by the fact that it dissolves without colour in cold acids, and that the intense coloration of the salts first becomes apparent after warming the solution. In addition to the above salts there also exist acid ones, e.g. C 20 H 20 N 8 C1 + 3HC1 (which yields a yellow-brown solution, FUCHSINE AND PARA-FUCHSINE 487 not a fuchsine-coloured one); these dissociate into the neutral salts and free acid upon the addition of much water. The formation of such acid salts is readily accounted for by the quinonoid formula. Rosenstiel has suggested the constitution Cl C(C 6 H 4 NH 2 ) 3 for para-fuchsine, according to which the salt is the chloride (ester) of a tertiary alcohol. Such a constitution, according to Hantzsch and Osswald (B. 1900, 33, 278), is not in harmony with known facts. Assuming the quinonoid structure II for para-fuchsine, then the conversion into para-rosaniline under the influence of alkalis should be preceded by the formation of an unstable quaternary ammonium hydroxide, which becomes transformed into the carbinol compound, para-rosaniline: C(C 6 H 4 NH 2 ) 2 C(C 6 H 4 NH 2 ) 2 NH 2 C1 NH 2 -OH Para-fuchsine. Para-rosaniline. Hantzsch and Osswald, by means of electrical conductivity determinations (B. 1900, 33, 278), have been able to indicate the presence of such an ammonium derivative in the solution which is formed when the dye is brought into contact with an equivalent of alkali. This compound is coloured in contra- distinction to the carbinol base, is very strongly basic and therefore strongly ionized, and is gradually transformed into the insoluble carbinol base. Para-rosaniline and the dye-bases generally are pseudo-bases corresponding in many respects with the pseudo-acids (p. 363). Formerly in the manufacture of magenta, a mixture of ani- line with o- and ^?-toluidine was oxidized by syrupy arsenic acid, stannic chloride or mercuric chloride or nitrate, &c.; in the modern method, a mixture of nitro-benzene with aniline and toluidine is heated with iron filings and hydrochloric acid (Coupler). Nitro-toluene may also be employed instead of nitro-benzene. If o-toluidine is present in the mixture of aniline and ^?-toluidine to be oxidized, rosaniline is formed, and if it is absent, para-rosaniline. When pure aniline is oxid- ized alone, it yields no fuchsine at all, but products of the nature of indulin. This is explained by the fact that for the 488 XXX. TRIPHENYL-METHANE GROUP formation of fuchsine a carbon atom is required which shall serve to link the benzene nuclei together, a so-called " methane- carbon"; in the action of carbon tetrachloride upon aniline, this carbon originates from the tetrachloride, and in the oxi- dation of a mixture of aniline and ^-toluidine, from the methyl group of the latter, as is shown in the following scheme : Para-rosaniline and rosaniline are also formed by heating p- diamino-diphenyl-methane (p. 476) with aniline and o-toluidine respectively, in presence of an oxidizing agent (B. 25, 302). When rosaniline is heated with hydrochloric or hydriodic acid to 200, it is split up into aniline and toluidines; when superheated with water, para-rosaniline yields jp-dihydroxy-ben- zophenone, ammonia, and phenol. When boiled with hydro- chloric acid, rosaniline breaks up into ^>-diamino-benzophenone and 0-toluidine (B. 16, 1928; 19, 107; 22, 988). A solution of fuchsine is decolorized by sulphurous acid, an additive- product, fuchsine-sulphurous acid, being formed. This solution, Schiff's reagent, is a delicate reagent for aldehydes, which colour it violet-red (see p. 127; B. 21, Kef. 149, &c.). Derivatives of Rosaniline 1. Methylated rosanilines (Hofmann, Lauth). The red colour of para-rosaniline and of rosaniline is changed into violet by the entrance of methyl or ethyl groups, the intensity of the latter colour increasing with an increasing number of these groups. The salts of hexamethyl-para-rosaniline have a magnificent bluish-violet shade. In the manufacture of these "methyl-violets" one may either (1) methylate rosaniline (by means of CH 3 C1 or CH 3 I); or (2) oxidize, instead of aniline, a methylated aniline such as dimethyl-aniline by means of cupric salts, whereby para-rosaniline derivatives result; or (3) allow phosgene to act upon dimethyl-aniline (or the latter to act upon the tetramethyl-diamino-benzophenone at first pro- duced) (cf. B. 17, Kef. 339): COC1 2 + 3C 6 H 6 .N(CH 3 ) 2 = C(OHXC 6 H 4 .N(CH 3 ) 2 ] 3 -f2HCl. In the last case hexamethyl-violet, termed " crystal violet " on account of the beauty of its crystals, is formed, while the HOSANILINE DERIVATIVES 489 hiethyl- violets prepared by methods (1) and (2) are mixtures of hexa-, penta-, and tetramethyl-rosanilines and are amorphous. The hydrochloride of the hexamethyl dye has the consti- tution : An interesting synthesis of this compound is by the action of the magnesium derivative of ^-bromo-dimethyl-aniline on tetra- methyl-diamino-benzophenone and subsequent treatment with hydrochloric acid (cf. Synthesis of Tertiary Alcohols, p. 356). The hexamethyl - carbinol no longer contains an amino- hydrogen atom, in consequence of which any further methyl chloride or iodide cannot effect an exchange of hydrogen for alkyl, but can only form an additive compound, a quaternary ammonium salt. Such addition causes a change of colour from violet to green; thus the compound is the dye methyl green or light green. Ethyl green (ethyl- hexamethyl rosaniline) is formed by the action of ethyl bro- mide on methyl violet. Various ethyl violets are known corresponding with the methyl violets. The hexa-substituted rosanilines, which con- tain benzyl as well as methyl or ethyl groups, are similar to crystal violet; their sulphonic acids form useful dyes, e.g. acid violet. 2. Phenylated rosanilines. By the successive entrance of phenyl-groups into rosaniline, there are formed in the first instance violet dyes, which change to blue when three phenyl groups have entered. Triphenyl-fuchsine or "aniline blue" is a beautiful blue dye, insoluble in water but soluble in alcohol. It is prepared by heating rosaniline with aniline in presence of benzoic acid, when ammonia is eliminated; or by the oxidation of phenylated aniline, i.e. diphenylamine, e.g. by means of oxalic acid. The latter supplies the "methane carbon atom", and the beautiful "diphenylamine blue" or spirit blue which is formed is a para-rosaniline derivative. Formic alde- hyde can also supply the methane carbon atom. Dyes insoluble in water are converted into soluble sulphonic acids. Such acids are Nicholson's blue, water blue, and light blue. Patent blue, new patent blue, are disulphonic acids. 490 XXX. TRIPHENYL-METHANE GROUP i. TRIHYDROXY-TRIPHENYL-METHANE, OR THE AURINE GROUP The hydroxy-analogues of para-rosaniline and rosaniline are aurine, C 19 H U 3 , and rosolic acid, C 20 H 16 3 : (OH . C 6 H 4 ) 2 C C 6 H 4 O or (OH C 6 H 4 ) 2 . C : C 6 H 4 : I I Aurine. These likewise possess the dye character, but, instead of being basic, they are acid dyes (phenol dyes); they are of far less value than the basic dyes which have been already described. They are formed when the diazonium derivatives of para- rosaniline or rosaniline are boiled with water (Caro and Wanlc- lyn, 1866): OH.C(C 6 H 4 N 2 S0 4 H) 8 + 3H 2 = OH.C(C 6 H 4 .OH) 3 + 3N 2 + 3H a S0 4 ; OH.C(C 6 H,.OH) S = (OH.C 6 H 4 ) 2 C:C6H 4 :0 + H S 0. The carbinol which must be produced here in the first instance is incapable of existence, and loses water. The constitutional formulae just given follow from this close relation to the rosani- lines. Aurine is also obtained by heating phenol with oxalic and sulphuric acids to 130-150 (Kolbe and Schmitt, 1859), ,the oxalic acid yielding the " methane carbon atom " ; rosolic acid results in an analogous manner from a mixture of phenol and cresol with arsenic and sulphuric acids. Phenol by itself yields no rosolic acid upon oxidation. Aurine and rosolic acid crystallize in beautiful green needles or prisms with a metallic lustre, dissolve in alkalis with a fuchsine-red colour, and are thrown down again from this solution by acids. The alkaline salts are decidedly unstable, aurine being but a weak phenol; at the same time it possesses a slightly basic character. An ammonium salt is known which crystallizes in dark-red needles with a blue lustre. Upon reduction there are formed the leuco- compounds leu- caurine, CH(C 6 H 4 -OH) 3 , and leuco-rosolic acid, OH-C 6 H 3 Me. CH(C 6 H 4 OH) 2 , both of which crystallize in colourless needles of phenolic character. Superheating with water transforms aurine into ^-dihydroxy-benzophenone, CO(C 6 H 4 OH) 2 , and phenol; superheating with ammonia, into para-rosaniline. 1HTH ALOPHENONE 491 4. tmPHENYL-METHANE-CARBOXYLIC-ACID, OB THE EOSIN GROUP (Of. Eaeyer, A. 183, 1; 202, 36) Triphenyl-methane-carboxylic acid, CH(C 6 H 5 ) 2 (C 6 H 4 .C0 2 H), obtained by the reduction of phthalophenone (see below), crys- tallizes in colourless needles melting at 162 and yields tri- phenyl-methane by the elimination of carbon dioxide. Triphenyl-carbinol-o-carboxylic acid, OH.C(C 6 H 5 ) 2 (C 6 H 4 . C0 2 H). The anhydride of this acid, which is termed phtha- lophenone, is obtained by heating phthalyl chloride with benzene and aluminic chloride (A. 202, 50), and forms plates, melting at 115. The acid itself is incapable of existence, but its salts are obtained by dissolving the anhydride in alkalis. Phthalophenone is on the one hand a triphenyl-methane de- rivative and on the other a derivative of phthalic acid; in accordance with the constitutional formula: it is to be regarded as diphenyl-phthalide (Phthalide, p. 462). Phthalophenone is the mother substance of a large series of dyes, which are derived from it by the entrance either of hydroxyl or of amino-groups. They are prepared by the action of phenols upon phthalic anhydride, and are termed Phthaleins. Phenol and resorcinol, for example, yield the compounds : and Phenol-phthalem Fluorescem. Quinonoid formulae are also possible, e.g. for phenol-phthalein, Free phenol-phthalein, which is colourless, probably has the lactone formula, and its coloured salts the quinonoid structure. Phenol-phthalein would then be a pseudo-acid (p. 364). See also H. Meyer, M. 1899, 20, 337; R. Meyer and Spendkr, B. 36, 2949; 38, 1318; Green and A. G. Perkin, 3. C. S. 1904, 398; Green and King, B. 39, 2365; 40, 3724; Stieglite, J. A. C. S. 25, 1112; Acree, Am. C. J. 39, 528, 771; 42 5 115. 492 XXX. TRIPHENYp-METHANE GROUP In the case of fluorescein a molecule of water is split off from two hydroxyls of the two resorcinol residues. Phthaleins of this kind (being hydroxy-phthalophenones) are converted by reduction into the hydroxy-derivatives of triphenyl-methane- carboxylic acid, which are termed "Phthalines"; e.g. phenol- phthalein into dihydroxy-triphenyl- methane -carboxy lie acid (C H OH) (i.e. phenol-phthaline), CH^n H t TO H' ^ e phthalines are Vxg-L-*-^ V/Vyg-*-*- colourless, and are to be looked upon as leuco-compounds of the phthaleins. The phthaleins include among themselves many dyes which are of technical value, e.g. the eosins (Caro, Baeyer, 1871). Phenol-phthalei'n is prepared by heating phthalic anhydride with phenol and sulphuric acid, or better, stannic chloride (or oxalic acid), to 115-120. It may also be obtained by nitrating diphenyl-phthalide, reducing the two substituting nitro-groups, and replacing the amino-groups thus formed by hydroxyl in the usual manner (A. 202, 68). It crystallizes from alcohol in colourless crusts; is nearly insoluble in water, but dissolves in dilute alkalis with a beautiful red colour which vanishes again on neutralization with acids; it is thus a valuable indi- cator. With very concentrated alkalis (KOH) phenol-phthalein yields colourless solutions probably containing metallic salts of a non-quinonoid structure. The ^-positions of the two hydroxy- groups have been proved by conversion into ^-dihydroxy- benzophenone. It yields a di-acetyl derivative melting at 143 and an oxime melting at 212. It is reduced by potash and zinc dust to phenol-phthaline (colourless needles), which dis- solves in alkalfto a colourless solution, but is readily reoxidized in this solution to phenol-phthalein. Fluorane, C 20 H 12 3 , which was formerly regarded as phenol- phthalein anhydride, is formed as a by-product in the phenol- phthalein melt, and is the mother substance of fluorescein. Both probably contain a pyrone ring (and hence the name Pyronines for the whole group of dyes), and the constitution of fluorane is represented as Fluorane, ^ ^> C CO-0 (Cf. R. Meyer, B. 1892, 25, 1385, 2118; 1893, 26, 1271.) FLUORESCEIN 493 Fluorescei'n, Dikydroxy-fluorane orresarcinol-phlhakw, C 20 H 12 5 f H 2 0, is prepared by heating phthalic anhydride and resor- cinol at 200. It forms a dark-red crystalline powder, and dis- solves in alcohol with a yellow-red colour, and in alkalis with a red colour and splendid green fluorescence. It is reducible to the phthaline " Fluorescin ", and with bromine yields red crystals of tetrabromo-fluorescein, the potassium salt of which, C 20 H(.Br 4 6 K 2 , is the magnificent dye eosin. Fluorescing dyes are likewise formed in an analogous manner from all the de- rivatives of 1 : 3-dihydroxy-benzene, in which position 5 is un- occupied, and the reaction is often made use of on the one hand for testing for ra-dihydroxy-derivatives, and on the other for phthalic anhydride or succinic anhydride. Instead of phthalic acid itself, chlorinated or brominated, &c., phthalic acids may be employed, so that, by gradually increasing the amount of halogen present, a whole series of yellow-red to violet-red eosins can be prepared, e.g. tetrabromo- di-iodo-eosin; these are known under the names of Erythrosin, Eose de Bengale, Phloxin, &c. It is worthy of note that many other dibasic acids (e.g. succinic) and also benzoic acid are capable of yielding nuorescing compounds. Gallein, C 20 H ] .,O 7 , is the dye obtained from pyrogallol and phthalic anhydride. The rhodamines are dyes closely allied to fluorescein. They are obtained by the condensation of phthalic anhydride and ^-alkylated-amino-phenols in presence of sulphuric acid. They contain the pyrone ring, and may be regarded as fluorescein in which the two hydroxyl groups have been replaced by tertiary amino-groups. Tetra-ethyl rhodamine, 6 H 3 -NEt 2 - is colourless, and has basic properties. The salts, e.g. sulphate, are red dyes, and probably possess a quinonoid structure. Tetraphenyl-methane, C(C 6 H 5 ) 4 . Many attempts to obtain this compound were made, but without success, until Gomberg (B. 1897, 30, 1897) succeeded in preparing it from triphenyl- bromo- methane. With phenyl-hydrazine this yields CPh 3 NH.NHPh, triphenylmethane-hydrazobenzene, which gives the corresponding azo-compound when oxidized, CPh 3 N:NPh, 494 XXXI. NAPHTHALENE GROUP and when this is heated nitrogen is evolved and tetraphenyl methane is formed. It is more readily prepared by the action of magnesium phenyl bromide on triphenyl-chloro- methane (B. 1906, 39, 1462). It forms colourless crystals, m.-pt. 282. XXXI. COMPOUNDS WITH CONDENSED BENZENE NUCLEI. NAPHTHALENE GROUP The higher fractions of coal tar contain hydrocarbons of high molecular weight, especially naphthalene, C^Hg, an- thracene, C 14 H 10 , and its isomeride phenanthrene. The first- named is found in the fraction between 180-200, and the two latter in that between 340-360. These compounds are of more complex composition than benzene, the molecule of naphthalene differing from that of the latter by C 4 H 2 , and those of anthracene and phenanthrene from that of naphthalene by the same increment. They closely resemble benzene as regards behaviour, and give rise to types of derivatives similar to those of benzene itself. They undoubtedly contain benzene nuclei, as anthracene yields benzoic acid upon oxidation, naphthalene phthalic acid, and phenanthrene diphenic acid. From their modes of forma- tion and behaviour it follows that in the building up of their molecules the benzene residues combine together in such a manner that 2 or (2 x 2) adjacent carbon atoms are common to both (cf. pp. 496 and 506). NAPHTHALENE GROUP Naphthalene, C 10 H 8 , was discovered by Garden in 1820. It is contained in coal-tar and crystallizes from the fraction which distils over between 180-200. These crystals are pressed to free them from oily impurities, and can then be further purified by treatment with small amounts of con- centrated sulphuric acid and subsequent sublimation. It is also formed when various carbon compounds are sub- jected to a red heat; thus, together with benzene, styrene, &c., by passing the vapours of methane, ethylene, acetylene, alcohol, acetic acid, &c., through red-hot tubes. Its presence in coal-tar may be due to some similar cause. The constitutional formula (p. 496) is largely based on the following syntheses: NAPHTHALENE GROUP 495 1. By the action of 0-xylylene bromide upon the sodium compound of the symmetrical ethane -tetracarboxy lie ester, ethyl tetrahydronaphthalene-tetracarboxylate is formed: r Na.C(C0 2 Et) 2 ,CH 2 .C(CO 2 Et) 2 and from this, naphthalene may be obtained by hydrolysis, the elimination of the carboxyl groups and subsequent oxi- dation (Baeyer and Perkin, B. 17, 448). 2. a-Naphthol, C^H^-OH, is produced by the elimination of water from y-phenyl-isocrotonic acid (Fittig and Erdmann, B. 16, 43; see p. 456), and yields naphthalene when heated with zinc dust. 3. J. F. Thorpe (P. 1905, 21, 305) has succeeded in syn- thesising a number of naphthalene derivatives by means of ethyl sodio-cyano-acetate, e.g. ethyl 1 : 3-diamino-naphthalene-2- carboxylate from ethyl sodio-cyano-acetate and benzyl cyanide. C 6 H 6 CH 2 ON + CO 2 Et CH 2 - CN C 6 H 5 .CH 2 .C(:NH).CH(C0 2 Et)CN, and this with sulphuric acid yields the bicyclic compound I, which is immediately transformed into the diamino-deriva- tive II. CH 2 CH-COoEt :NH The same compound may be synthesised from ethyl sodio- cyano-acetate by the following stages (J. C. S. 1907, 91, 578). Condensed with o-toluyl chloride, CH 3 C 6 H 4 ^CO'C1, it yields ethyl cyano-0-toluyl-acetate, CH 3 - C 6 H 4 CO CH(CN)C0 2 Et, and this when heated with ammonium acetate gives the corre- sponding imino-derivative, CH 3 C^ C( : NH) CH(CN)C0 2 Et, ethyl /3-imino-a-cyano-/3-o-tolyl-propionate, which reacts with acids giving compound I. l:4-Naphthalene-diamines have been prepared by similar methods, using derivatives of phenyl-butyric acid (J. C. S. 1907, 91, 1004). Constitution. That naphthalene contains a benzene nucleus, in which two hydrogen atoms occupying the ortho- position are replaced by the group (C 4 H 4 )", follows not only from its oxidation to phthalic acid, but also from its formation from 496 XXXI. NAPHTHALENE GROUP 0-xylylene bromide. And that the four carbon atoms of this group are linked to one another without branching is shown by the formation of a-naphthol. CH CO ' TT a-Naphthol. y-Phenyl-iso-crotonic acid That there are actually two so-called " condensed " benzene nuclei present in the naphthalene molecule is a necessary con- sequence of the fact that phthalic acid or its derivatives ensue on the breaking up of the compound, not only from one but from both of the rings. For instance, a-nitro-naphthalene (p. 499) on oxidation yields nitro-phthalic acid, C 6 H 3 (NO 2 )(C0 2 H) 2 ; consequently the ben- zene ring to which the nitro-group is linked remains intact. But, on reducing the nitro-naphthalene to amino-naphthalene and oxidizing the latter, no amino-phthalic acid nor any oxi- dation product of it is obtained, but phthalic acid itself, a proof that this time the benzene nucleus to which the amino-group is attached has been destroyed, and that the other has remained intact (Graebe, 1880; for an analogous proof by him, see A. 149, 20). Naphthalene therefore receives the constitutional formula (Erlenmeyer, 1866): H //^ /^ H H There is the same difficulty in deciding between the double bond KekuU formula and the centric formula as in the case of benzene. The above constitutional formula is in complete harmony with the number of isomeric forms in which naphthalene derivatives occur, and also with the formation of additive compounds with hydrogen or chlorine. (Cf. Bamberger^ A, 357, 1; B. 1891, 24, 2054.) NAPHTHALENE 497 This union of two benzene nuclei is accompanied by a modification of their properties, so that naphthalene and its derivatives differ characteristically from benzene in many respects. Such differences show themselves, for instance, between the naphthylamines and aniline, the naphthols and phenol; and also especially in the greater readiness with which the naphthalene derivatives are reduced, the latter taking up as many as four atoms of hydrogen easily. After such addition the reduced nucleus is found to have entirely lost the characteristics of a benzene nucleus, and to have become similar in properties to an alphyl radical, whereas the non-reduced nucleus assumes the character of a benzene nucleus in its entirety (Bamberger). (See the Tetrahydro-deriva- tives of the Naphthylamines and Naphthols, pp. 500 and 502.) Properties. Naphthalene crystallizes in glistening plates, is insoluble in water, sparingly soluble in cold alcohol and ligroin, but dissolves readily in hot alcohol and ether; it melts at 80 and boils at 218. It has a characteristic tarry smell, and is distinguished by the ease with which it sublimes and volatilizes with steam. With picric acid it yields an additive compound, C 10 H 8 , OH CgH 2 (N0 2 ) 3 , crystallizing in yellow needles and melting at 149 . It takes up hydrogen far more readily than benzene does, yielding di- and tetrahydronaphthalenes, C 10 Hp and C 10 H 12 ; both of these are liquids of pungent odour which re- generate naphthalene again when heated. By the powerful action of hydriodic acid and phosphorus, the second benzene nucleus can also be made to take up hydrogen, so that a hexa- hydro-, Q, H 14 , and finally a dekahydronaphthalene, C 10 H 18 , are formed. It also yields additive products with chlorine more readily than benzene does, e.g. naphthalene dichloride, C 10 H 8 C1 2 , and -tetrachloride, C 10 H 8 -C1 4 (m.-pt. 182); the latter is oxi- dized to phthalic acid more easily than naphthalene itself, hence that acid is sometimes prepared from it on the large scale. Naphthalene is principally used for the preparation of phthalic acid (for eosin, indigo, &c.), and of naphthylamines and naph- thols (for azo-dyes); also for the carburation of illuminating gas. It is a powerful antiseptic, and is employed therapeuti- cally. NAPHTHALENE DERIVATIVES The number of substitution products in the case of naph- thalene is greater than with benzene. (B480) 21 498 XXXI. NAPHTHALENE GROUP The mono-derivatives invariably exist in two isomeric forms, the a- and ^-compounds, e.g.: C 10 H 7 C1 (a- and /3-chloro-naphthalene). C 10 H 7 NH 2 (a- and jS-naphthylamine). C 10 H 7 OH (a- and /3-naphthol). C 10 H 7 CH 3 (a- and /3-methyl-naphthalene). As in the case of the benzene compounds, the existence of two series of mono-derivatives has not only been established empirically, but it has also been proved (in a manner similar to that given on p. 329, et seq.) that in the naphthalene mole- cule two sets of hydrogen atoms (the a and /?, a = 1, 4, 5, 8; /3 = 2, 3, 6, 7) have an equal value as regards one another, but the atoms of the one set differ from those of the other, so that the a- and the /3-positions occur severally four times, i.e. twice in each benzene nucleus (Atterberg). The above constitutional formula for naphthalene satisfies these conditions, since, according to it, the positions 1, 4, 5, and 8 are severally equal and also the positions 2, 3, 6, and 7, but not the positions 1 and 2. The conception that in the a-compounds the position 1, 4, 5, or 8 is occupied is due to Liebermann (A. 183, 225), Eeverdin and Noelting (B. 13, 36), and Fittig and Erdmann (cf. the formation of a-naphthol given above). With regard to the di-derivatives of naphthalene, a consider- able number of isomerides of a good many are known; accord- ing to the naphthalene formula, ten are theoretically possible in each case when the two substituents are the same, and fourteen when they are different. The ten possible isomerides are 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 2:3, 2:6, and 2:7. All other combinations are identical with one of these ten. According to Armstrong and Wynne ten dichloro- and fourteen trichloro- naphthalenes are actually known. (See also B. 1900, 33, 1910, 2131.) The position 1:8 is termed the "peri-" position; it resembles the ortho- position to some extent, e.g. >m-naphthalene-dicar- boxylic acid like an o-dicarboxylic acid yields an anhydride. The homologues of naphthalene are of comparatively small importance, and are usually prepared by Fittig's or by Friedel and Crafts' synthesis. Most of them are liquids, and on oxi- dation yield acids resembling benzoic acid. -Bromo-naphthalene can be prepared directly by brominat- ing naphthalene, and is partially converted into the y&-compound NAPHTHYLAMINES 499 when heated with aluminium chloride. Its bromine atom is somewhat more readily exchangeable than that of bromo- benzene, but cannot be eliminated by boiling with alkalis. Interesting methods of formation of the halogen derivatives are by heating the hydroxy-, nitro-, or sulphonic acid deriva- tives with phosphorus pentachloride. a-Nitro-naphthalene, C 10 H 7 N0 2 (Laurent, 1835), is formed by the direct nitration of naphthalene. It crystallizes in yellow prisms, melts at 61, boils without decomposition, and readily yields 1 : 5 and 1:8 di- and various tri- and tetra-nitro- naphthalenes upon further nitration. On reduction it is con- verted into a-naphthylamine. The position of the nitro-group has been established by conversion of this compound into a- naphthol. The isomeric /?-nitro-naphthalene can be obtained indirectly by diazotizing /3-naphthylamine, and acting on the product with sodium nitrite in presence of cuprous oxide (B. 20, 1494; 36, 4157); it crystallizes in bright yellow needles melting at 79. a-Naphthylamine, C 10 H 7 NH 2 (Zinin), forms colourless needles or prisms, melts at 50, boils at 300, and is readily soluble in alcohol. It can be obtained by reducing the a-nitro- compound, and also readily by heating a-naphthol with the double compound of calcium chloride arid ammonia, while aniline can only be prepared from phenol in a similar manner with difficulty: Ci H 7 .OH + NH 3 = C 10 H r NH 2 + H 2 0. It possesses a disagreeable fsecal-like odour, sublimes readily, and turns brown in the air. Certain oxidizing agents, such as ferric chloride, produce a blue precipitate with solutions of its salts, while others give rise to a red oxidation product; chromic anhydride oxidizes it to a-naphthaquinone. In other respects it resembles aniline; for differences, see B. 23, 1124. Its hy- drochloride is only sparingly soluble in water. The isomeric /3-naphthylamine, C 10 H r NH 2 (Liebermann, 1876), is most conveniently prepared by heating /?-naphthol either in a stream of ammonia or with the double compound of zinc chloride and ammonia. It is now generally prepared by the action of ammonium hydroxide and sulphite on /2-naphthol (C. C. 1901, 1, 349). Naphthyl ammonium sulphite is formed as an intermediate product and reacts with the ammonia, yield- ing naphthylamine and ammonium sulphite. This reaction is frequently used for transforming derivatives of a and ft naph- thol into corresponding amino-compounds. The reaction is reversible and can be used for replacing NH 2 by OH. 500 XXXI. NAPHTHALENE GROUP /3-Naphthylamine crystallizes in nacreous plates, melts at 112, boils at 294, and has no odour. It is more stable than a-naphthylamine, and is not coloured by oxidizing agents. Both of these naphthylamines can be converted into tetra- hydro-compounds by the action of sodium and amyl alcohol (i.e. nascent hydrogen) upon them. The tetrahydro-a-naphthyl- amine resembles its mother substance closely in most of its properties, e.g. it can be diazotized and has entirely assumed the character of aniline; the hydrogen atoms have entered the nucleus which does not contain the amino-group. It is termed aromatic or "ar"-tetrahydro-a-naphthylamine. (Formula I.) Tetrahydro-^-naphthylamine, on the other hand, is not diazo- tized by nitrous acid, but transformed into a very stable nitrite. Here it is the benzene nucleus containing the amino-group which has become reduced; the compound has assumed the properties of an amine of the fatty series, and is termed alicydic or "ac"-tetrahydro-/3-naphthylamine. (Formula II.) The a-compound is oxidizable to adipic acid (p. 231), and the ^-compound to o-hydrocinnamo-carboxylic acid, C 6 H 4 <^2^ CH 2' C0 2 H . (Cf. Bamlerger and others, B. 21, 847, 1112, 1892; 22, 625, 767; 23, 876, 1124.) H NH 2 II \ An ac-tetrahydro-o- and an ar-tetrahydro-^-naphthylamine have also been prepared. From both naphthylamines there are derived, as in the benzene series, methyl- and dimethyl-naphthylamines, phenyl- a- and -/3-naphthylamines (which are of technical importance), nitro-naphthylamines, diamino-naphthalenes or naphthylene- diamines, C 10 H 6 (NH 2 ) 2 , diazonium- compounds (which are in every respect analogous to the diazonium salts of benzene, especially in the formation of azo-dyes, many of which are of great technical importance), diazo-amino-compounds, &c. The diazo-amino-naphthalene, C 10 H r N : N NH C 10 H r , which is formed by the action of nitrous acid upon a-naphthyl- amine, readily undergoes a molecular transformation (like the corresponding benzene compound) into amino-azo-naphthalene, NAPHTHALENE SULPHONIC ACIDS. NAPHTHOLS 501 C 10 H 7 N : N C 10 H 6 NH 2 . This latter compound crystallizes in brownish-red needles with a green metallic lustre, and can be diazotized, its diazo-compound yielding a-azo-naphthalene, CjgHy.NiN'CjoHf (red to steel-blue glistening prisms), when boiled with alcohol. This last can either not be prepared at all or only with great difficulty by the methods which hold good for azo-benzene. A mixture of naphthalene a- and /3-sulphonic acids, C 10 H 7 S0 2 OH, is obtained by warming naphthalene to 80 with con- centrated sulphuric acid. They may be separated by aid of their calcic or baric salts, as the /3-sulphonates are less soluble than the a-salts. The a-acid is transformed into the /?-acid when heated with concentrated sulphuric acid, and hence the chief product obtained by sulphonating naphthalene at 160 is the /3-acid. The sulphonic acid radicals in these compounds may be readily replaced by hydroxyl or cyanogen by the usual methods. Naphthalene -disulphonic acids, C 10 H 6 (SO 3 H) 2 . Two iso- meric /?-/?-acids (2:6 and 2:7) are formed when naphthalene is heated with concentrated sulphuric acid at 160-200, while an a-a-acid (1:5) is obtained with chloro-sulphonic acid, S0 3 HC1, in the cold, and the a-/?-acid (1:6) from the /?-mono-sulphonic acid in a similar manner. Naphthylaxnine - mono - sulphonic acids, NH 2 C 10 H 6 S0 2 OH. Thirteen isomers of these are known (7 a- and 6 /?-). Naphthionic acid (NH 2 : S0 3 H = 1 : 4) is obtained by the sulphonation of a-naphthylamine ; it is employed in the pre- paration of azo-dyes, as are also several of its isomers and various naphthylamine - disulphonic acids. These last are obtained (a) directly from a- or /3-naphthylamine, or (b) by nitrating the naphthalene-sulphonic acids and then reducing the nitro- to an amino-group. a- and /?-Naphthols, 10 H 7 OH, which are present in coal-tar, can be easily prepared, not only from the naphthalene-sulphonic acids as above, but also by diazotizing the naphthylamines. They crystallize in glistening plates, have a phenolic odour, and dissolve readily in alcohol and ether but only sparingly in hot water. a-Naphthol (Griess, 1866) melts at 95 and boils at 282, while /3-naphthol (Scha/er, 1869) melts at 122 and boils at 288; both of them are readily volatile at ordinary temperatures. They possess a phenolic character but never- theless resemble the alcohols of the benzene series more than tho phenols, their hydroxy-groups being much more reactive 502 XXXI. NAPBT&ALENE GROUP than those of the latter, e.g. they can be readily replaced by amino-groups (see above). /?-Naphthol is an antiseptic. ar-Tetrahydro-a-naphthol, C 10 H 7 H 4 .(OH), obtained by reducing a-naphthol, has the character of a pure phenol, and not that of a-naphthol. A mixture of ar- and ac- tetrahydro- /2-naphthols is obtained from /8-naphthol, the ar-compound corresponds with phenol and the ac-compound with alcohol. Ferric chloride oxidizes a- and /3-naphthols, with production of violet and greenish colorations respectively, to di-naphthols, C 20 H 12 (OH) 2 , which correspond with the dihydroxy-diphenyls (p. 473), and are derivatives of di-naphthyls (p. 504). The cautious oxidation of a-naphthol yields o-cinnamo-oarboxylic acid, C0 2 H.C 6 H 4 .CH:CH.C0 2 H, and that of /3-naphthol, o-carb'oxy-phenyl-glyoxylic acid, C0 2 H . C 6 H 4 CO C0 2 H. The naphthols yield alkyl and acyl derivatives. The ethers are formed by the action of an alcohol and hydrogen chloride on the naphthols. /3-Naphthyl-methyl-ether, C 10 H r -0'CH 3 , is the nerolin used as a perfume. From the naphthols, as from the phenols, there are derived nitro-, dinitro-, trinitro-, and amino-compounds, &c. The calcium salt of dinitro-a-naphthol, C 10 H 5 (N0 2 ) 2 OH, is known as Martins' yellow or naphthalene yellow, and its sulphonic acid, naphthol yellow S or fast yellow, is a valuable dye. Amino - naphthols, C 10 H 6 (NH 2 )(OH), are obtained by the reduction of nitro-naphthols; like the amino-phenols they are readily oxidized in the air. (NH 2 :OH in the a-compound = 1:4, in the /^-compound = 1:2.) A number of naphthol-mono-, -di-, &c., sulphonic acids are known, also amino-naphthol-sulphonic acids, which are of great technical value. Among these may be mentioned 1 : 4-naph- thol- sulphonic acid (Nevile and JTinther), from naphthionic acid, the 2:8-acid, the 2:6-acid, the /?-naphthol-disulphonic acids E (2:3:6) or "It-salt", and G (2:6:8) or "G-salt". l-Amino-8-naphthol-3:6-disulphonic acid = H acid. Sodium l-amino-2-naphthol-6-sulphonate is used as a photo- graphic developer under the name of Eikonogen. Azo-dyes. A series of very important azo-dyes (see also under Benzidine, p. 472) are produced by the action of dia- zonium compounds, and of diazo-naphthalene-snlphonic acids upon the naphthylamines and naphthols, and especially upon the sulphonic acids of these, e.g.: Benzene-azo-a-naphthylamine, C 6 EL N : N C-, H 6 NH 2 ; Orange II, S0 8 Na.C 6 H 4 .N:N.C 10 H 6 .OH[/?]; NAIHTHAQUINONES 503 Ponceau 2R, from diazotized xylidine and "E-salt"; Fast Red C ("EchMh"), S0 3 Na.C 10 H 6 .N:N.C 10 H 5 (pH)(S0 3 Na), from naphthionic acid and l-naphthol-4-sulphonic acid; Bie- brich Scarlet, S0 3 Na . C 6 H 4 - N : N . C 6 H 4 . N : N C 10 H 6 (OH), from amino-azo-benzene-sulphonic acid and /3-naphthol; Brilliant Black, (SOsNaJjC^.NiN.Cj^.NrN.O^OHJfSOsNaJa, from naphthylamine-disulphonic acid, a-naphthylamine, and "K-salt"; Palatin Black, S0 3 Na.C 6 H 4 .N 2 .C 10 H 3 (N 2 C 10 H 7 ) (NH 2 )(OH)(S0 3 Na), from diazobenzenesulphonic acid, a-azo- naphthalene, and l-amino-8-naphthol-4-sulphonic acid. Quinones of the Naphthalene Series. Three isomeric quin- ones, C 10 H 6 2 , are known; two correspond with para and ortho benzoquinones. a-Naphthaquinone may be obtained by the oxidation of naphthalene, a-naphthylamine, l-amino-4-naphthol, l:4-di- hydroxy-naphthalene, and of various derivatives of naphtha- lene containing substituents in the a-positions, by chromic acid. It crystallizes in yellow rhombic plates, melts at 125, and is the complete analogue of ordinary quinone, having a similar odour and being volatile with steam. It can be reduced to 1 : 4-dihydroxy-naphthalene by sulphurous acid, and can yield a dioxime, hence its constitution as a para- or 1 : 4-quinone. (Formula I.) /2-Naphthaquinone (II) has no odour and is not volatile, being thus more like phenanthraquinone. It can be obtained by the oxidation of l-amino-2-naphthol, and when reduced with sulphurous acid yields 1 :2-dihydroxy-naphthalene; hence its constitution as a 1 : 2 or orthoquinone. It decomposes at 115 without melting and crystallizes in red needles: 2 : 6-Naphthaquinone (III), isomeric with the a- and /?-com- pounds, forms odourless, non- volatile, yellowish -red prisms, and is a strong oxidizing agent. Hydroxy-naphthaquinones are known; the common one is 2-hydroxy-a-naphthaquinone; juglone is the isomeric 5-hy- droxy-compound, and occurs in nut shells; naphthazarine, "alizarin black", is a valuable dye which is prepared by act- ing upon a-dinitro-naphthalene with zinc and sulphuric acid, 504 XXXII. ANTHRACENE AND PHENANTHRENE GROUPS comports itself like the alizarin dyes; it is the "alizarin" of the naphthalene series. Carboxylic Acids. The naphthoic acids, C 10 H 7 C0 2 H, can be obtained by saponifying the cyano-naphthalenes and also by the other synthetical methods given for the acids of the benzoic series. They crystallize in fine needles sparingly soluble in hot water, and break up into naphthalene and carbon di- oxide when distilled with lime. From them are derived the hydroxy-naphthoic acids, C 10 H 6 (OH)(C0 2 H), which are re- lated to salicylic acid or its isomers. Among the naphthalene- dicarboxylic acids, C 10 Hg(C0 2 H) 2 , which are known may be mentioned naphthalic acid, (1:8), which at a somewhat high temperature yields an anhydride similar to phthalic anhydride. Phenyl-naphthalene, C 10 H 7 (C 6 H 5 ), has also been prepared; it is a compound built up of a naphthalene and of a benzene nucleus, and is therefore analogous to diphenyl, G 6 H 5 C 6 H 5 . The same applies to: Di-naphthyl, C 10 H 7 C 10 H 7 , which yields derivatives (e.g. the di-naphthols, see p. 502) analogous to those of diphenyl. The three modifications which are theoretically possible, namely, the a-a-, /?-/?-, and a-/?-compounds, are known. Another derivative of naphthalene is acenaphthene, C 12 H 10 , ^2 (1:8), which is found in coal-tar. It crystal- )H 2 lizes in colourless prisms, melts at 95, boils at 277, and yields naphthalic acid on oxidation. XXXII. THE ANTHRACENE AND PHENAN- THRENE GROUPS A, Anthracene Anthracene, C 14 H 10 (Dumas and Laurent, 1832; Fritzsche, 1857), is formed, together with benzene and naphthalene, by the destructive distillation of coal and, generally, by the pyrogenous reactions which give rise to these products, e.g. by passing CH 4 , C 2 H 6 , C 2 H 2 , the vapour of alcohol, &c., through red-hot tubes. Although coal-tar contains only some 0'25-0'45 per cent of anthracene, it is the chief source from which this hydrocarbon ANTHRACENE 505 is obtained. The fraction of coal-tar distilling above 270 and known as anthracene oil yields, on further distillation and digesting with solvent naphtha, a solid mass known as 50- per-cent anthracene, which is then distilled with one-third of of its weight of potassium carbonate. This serves to remove carbazole (p. 473), which yields a non- volatile potassium de- rivative - 6 yNK, and the distillate consists of anthracene C 6 H/ and phenanthrene. The phenanthrene is removed by extrac- tion with carbon disulphide, and the anthracene crystallized from benzene. The following are some of the more important methods by means of which the hydrocarbon has been synthesised, and they throw considerable light upon its constitution: 1. By heating 0-tolyl phenyl ketone with zinc dust (B. 7, 17) : 2. Together with dibenzyl, by heating benzyl chloride with water at 200 (B. 7, 276): 4C 6 H 5 .CH 2 C1 = C 14 H 10 + C 14 H I4 + 4HC1. 3. From o-bromo-benzyl bromide and sodium in ethereal solution dihydro- anthracene is at first formed, and this is converted by oxidation (which is partly spontaneous during the above reaction) into anthracene (B. 12, 1965): 4. By heating benzene with symmetrical tetrabromo-ethane and aluminic chloride (Anschutz, B. 16, 623) : BrCHBr I BrCHBr I + C 6 H 6 = C 6 H 4 rCH 5. When phthalic anhydride is heated with benzene and aluminic chloride, o-benzoyl-benzoic acid is formed, and this when heated with phosphoric anhydride yields anthraquinone 506 XXXlI. ANTHRACENE AND FHENANTHRENE GROtJPS (Behr and v. Dorp, B. 7, 578), which on reduction with zinc dust gives anthracene: -geH, = Co H 4 <gg>C e H 4 +H 2 0; /ITT C 6 H 4 <gg>C 6 H 4 + 6H = C 6 H 4 <^ >C 6 H 4 -f 2H 2 0. 6. When a mixture of wi-xylene and styrene is treated with concentrated sulphuric acid, there is formed a-tolyl-fl-phenyl- propane, CH 3 C 6 H 4 CH 2 CH<^Q|r 5 , which decomposes almost quantitatively into methane, hydrogen, and methyl-anthracene when strongly heated (B. 23, 3272). Constitution. From mode of formation 5, the anthracene molecule is seen to contain two benzene nuclei, C 6 H 4 , joined together by a middle group, C 2 H 2 . The carbon atoms of this middle group are likewise linked together, as is seen from mode of formation 4, and take up the 0-position with regard to each other on one or other of the benzene nuclei (on one nucleus according to methods of formation 1 and 5, and on the other according to method 3; for further proofs of this, see e.g. v. Pechmann, B. 12, 2124). The constitution of an- thracene is thus the following (Graebe and Liebermann, A. Suppl. 7, 313): CH CH CH 3H or The two carbon atoms of the middle group thus form a new hexagon-ring with the carbon atoms of the benzene nuclei to which they are linked, so that anthracene may also be looked upon as being built up by the conjunction of three benzene / CH \ nuclei. Besides the formula C 6 H 4 <^ I yO 6 H 4 , the "quinoid" QJT CH formula CHTT>CH has also to be taken into consider- ation (Armstrong, P. 1890, 101; Kehrmann, B. 1894, 21, 3348), Properties and Behaviour. Anthracene crystallizes in colour less plates which show a magnificent blue fluorescence. It is ANTHRACENE DERIVATIVES 507 insoluble in water and dissolves only sparingly in alcohol and ether, but readily in hot benzene. It melts at 213, boils above 351, and with picric acid yields an additive compound which crystallizes in beautiful red needles melting at 138. Anthracene is transformed by sunlight into the polymeric para-anthracene, (C 14 H 10 ) 2 . When reduced with hydriodic acid and phosphorus it takes up, in the first instance, two atoms of hydrogen, with the formation of 9:10-dihydro-anthracene, (see p. 505, mode of formation 3). This crystallizes in colour- less plates, melts at 107, and is readily soluble in alcohol. It sublimes readily and distils without decomposition, but yields anthracene at a red heat or when warmed with concentrated sulphuric acid. Further addition of hydrogen yields the hydrides C 14 H lfl and, finally, C 14 H 24 . DERIVATIVES OF ANTHRACENE Theoretically three isomeric mono-derivatives are possible in each case, viz., the a-, /?-, and -/-compounds : since in the graphical formula given on the preceding page, 1 = 4 = 5 = 8 = a, 2 = 3 = 6 = 7 = ft and 9 = 10 = 7. The observed facts are in complete accordance with this. The position of the substituting group can usually be deter- mined either by an examination of the oxidation products, e.g. if it be in the y-position it will be eliminated and anthra- quinone formed; or it is arrived at from the synthesis of the compound, e.g. in the case of alizarin, the formation of which from catechol and phthalic acid shows that its two hydroxyls are contained in one and the same benzene nucleus. The number of di-substituted derivatives is large, for example, when both substituents are alike, 15 isomerides are theoretically possible. 508 XXXII. ANTHRACENE AND PHENANTHRENE GROUPS Numerous derivatives of anthracene are known, e.g. halogen-, nitro-, amino-, and sulphonic acid derivatives. Hydroxy-anthracenes. The a- and /^-compounds are termed a- and /3-anthrols; they are obtained by fusing the correspond- ing sulphonic acids with alkali, and in their properties closely resemble phenols and naphthols. y-Hydroxy-anthracene or anthranol may be obtained by- reducing anthraquinone with zinc and acetic acid, or syntheti- cally, by the action of concentrated sulphuric acid on o- benzyl-benzoic acid at 80 : It is readily oxidized to anthraquinone, and with hydroxyl- amine yields anthraquinone oxime. Anthraquinone, C 14 H 8 O 2 (Laurent, 1834), is readily obtained by oxidizing anthracene with chromic acid mixture (which is the method followed on the large scale), or with chromic an- hydride and glacial acetic acid, and is also produced when calcium benzoate is distilled. It crystallizes in yellow prisms or needles soluble in hot benzene, melts at 285, sublimes with great readiness, and is exceedingly stable as regards oxidizing agents. Hydriodic acid at 150 reduces it either to anthracene or its dihydride, while fusion with potash converts it into benzoic acid. It possesses more of a ketonic than of a quinonic character (Zincke, Fittig), as it is not reduced by sulphurous acid, and gives an oxime with hydroxylamine. It yields mono- and dibromo-, nitro- and sulphonic - acid derivatives. Anthraquinone /3-mono-sulphonic acid crystal- lizes in yellow plates, and is formed by the action of sul- phuric acid under normal conditions, but in the presence of mercury salts the isomeric a -acid is obtained; of the di- sulphonic acids two are formed directly from anthraquinone, and two may be prepared by the oxidation of the correspond- ing anthracene-disulphonic acids. Fusion of the sulphonic acids with potash does not generally yield the analogous hydroxy-compounds in theoretical quantity, oxygen being usually absorbed from the air at the same time ; thus the mono-sulphonic acids yield mono- and dihydroxy-, and the di-sulphonic acids di- and trihydroxy-anthraquinones. In practical working the theoretical amount of chlorate of ALIZARIN 509 potash required is added to the "melt". Prolonged fusion with potash tends to form hydroxy-benzoic acids. Various hydrpxy-anthraquinones can also be prepared by the synthetical mode of formation 5, p. 505, viz., from phthalic anhydride and the mono- or dihydroxy-benzenes (Baeyer and Caro, B. 7, 792; 8, 152), e.g.: phenol yields by this method the two hydroxy-anthraquinones (yellow needles), catechol yields alizarin, quinol yields quini- zarin, and so on. The hydroxy-derivatives are further pro- duced by fusing chloro- and bromo-anthraquinones with potash, while m- hydroxy-benzoic acid can be converted directly by sulphuric acid into anthraflavic acid, water being eliminated. Cf. A. 240, 245. Alizarin, 1 : 2-dihydroxy-anthraquinone, C U H 8 4 , is the most important constituent of the beautiful red dye of the madder root (Eubia tinctorum), which has been known for ages, being present in the latter as the readily decomposable glucoside, Euberythric acid, C^HggO^; in addition to alizarin, madder also contains purpurin. It is manufactured on the large scale by fusing anthraquinone-/3-sulphonic acid with potassic hy- droxide and chlorate (Graebe and Liebermann, Caro, Perkin, B. 3, 359; A. 160, 130). It crystallizes in magnificent red prisms or needles of a glassy lustre, melts at 289, and can be sublimed; it dissolves readily in alcohol and ether, only sparingly in hot water, but, as a phenol, very readily in alkalis to a violet-red solution. It yields insoluble coloured compounds the so-called "lakes" with metallic oxides, the alumina and tin lakes being of a magnificent red colour, iron lake violet-black, and lime lake blue. In the Turkey Red manufacture, for instance, the materials to be dyed are previously mordanted with acetate of alumina or with " ricinoleic-sulphuric acid". Its constitutional formula is based on the following con- siderations: (a) Its conversion into anthracene when heated with zinc dust (Graebe and Liebermann, B. 1868, 1, 49; A. Sup. 7, 297); (b) its formation by fusing dibromo-anthraquinone or anthraquinone-sulphonic acid with potash; (c) its synthesis from phthalic anhydride and catechol. All these indicate that it is a dihydroxy-anthraquinone 510 XXXII. ANTHRACENE AND PHENANTHRENE GROUPS with the two hydroxy-groups in the 0-positions with respect to one another: CO OH S\ yVAA,. /\ H /Y Vl 011 2:3 or 1:2. w/J The fact that two isomeric mono-nitro-derivatives (with the nitro-group in the same nucleus as the two hydroxy-groups) have been prepared is a proof of the positions 1:2 for the hydroxy-groups. C(OH) Anthrarobin, dihydroxy-anthranol, C 6 H 4 <( ^>C 6 H 2 (OH) 2 , X CH / obtained from alizarin, ammonia, and zinc dust, is a yellowish- white powder which yields alizarin on oxidation; on account of its reducing properties it is used in skin diseases. Nitric peroxide converts alizarin into /2-nitro-alizarin or ali- zarin orange, C 14 H 7 (N0 2 )0 4 , a yellowish-red dye; and this with glycerol and sulphuric acid (the Skraup reaction, p. 542), yields alizarin blue, C 17 H 9 N0 4 (see Quinoline), a valuable blue dye which is converted by fuming sulphuric acid into alizarin green. Purpurin, l:2-A-trihydroxy-, anthrapurpurin, 1:2:7 -trihydroxy-, and flavopurpurin, l:2:Q-trihydroxy-anthraquinone, are also valu- able dyes which are manufactured on a large scale; the same applies to the isomeric compound anthragallol, l:2:3-trihydroxy- anthraquinone, or "anthracene brown", which is prepared by acting on a mixture of gallic and benzoic acids with concen- trated sulphuric acid. Tetra-, penta-, and hexa-hydroxyanthraquinones are also used as dyes. (B. 1890, 23, 3739; J. pr. 43, 237, 246.) Alizarin bordeaux is a l:2:5:8-tetrahydroxy- and alizarin- cyanine 1:2:4:5: 8-pentahydroxy anthraquinone. According to v. Kostanecki the colouring power of these com- pounds is connected with the presence of two hydroxyls in the ortho-position to one another. For Indanthrene dyes see B. 36, 3410. B. Phenanthrene Phenanthrene (Fittig and Ostermeyer, 1872, A. 166, 361) which is isomeric with anthracene, accompanies this hydro- carbon in coal-tar. It crystallizes in colourless glistening PHENANTHRENE 511 plates, dissolves in alcohol more readily than anthracene (yielding a blue fluorescent solution), melts at 99, and boils at 340. It may be separated from anthracene by partial oxidation and subsequent distillation, as the latter is more readily attacked. Oxidizing agents convert it into diphenic acid (p. 474). Its picrate crystallizes in yellow needles melt- ing at 145. It may also be obtained: 1. By leading the vapour of tolu- ene, stilbene, dibenzyl or 0-ditolyl through a red-hot tube, thus : CH, OEL-CH 2. Together with anthracene from 0-bromo-benzyl bromide and sodium. 3. A recent synthesis by Pschorr (B. 1896, 29, 496; 32, 162, 176; 33, 496) is from 0-nitro-benzaldehyde. This with sodic phenyl-acetate and acetic anhydride (Perkiris synthesis, p. 441) yields a-phenyl-o-nitro-cinnamic acid, N0 2 C 6 H 4 CH : CPh C0 2 H. When this is reduced, diazotized, and treated with copper powder, /3-phenanthrene-carboxylic acid is formed, C 6 H 4 .CH , and when carbon dioxide is eliminated this ( C 6 H 4 CC0 2 H yields phenanthrene. Numerous phenanthrene derivatives have been synthesised in a similar manner. (See also Robe, B. 1898, 31, 1896.) The formation of phenanthrene from 0-ditolyl, and its oxi- C 6 H 4 .C0 2 H dation to diphenic acid, , show that it is a diphenyl derivative, and that it contains a carbon atom linked to each benzene nucleus; this carbon atom is joined to the corre- sponding one by a double bond, as is shown, e.g., by its C 6 H 5 .CH formation from stilbene, , a reaction completely analogous to the preparation of diphenyl from benzene. Since diphenic acid is a di-ortho-diphenyl-dicarboxylic acid (Schultz, A. 196, 1 ; 203, 95), phenanthrene is also a di-ortho-derivative and possesses the following constitution: CH CH ^ C CH CVH 4 .CH r 512 XXXII. ANTHRACENE AND PHENANTHRENE GROUPS According to the above formula, the two CH-groups form a new hexagon ring with the carbon atoms of the two benzene nuclei to which they are linked, so that phenanthrene like anthracene may be looked upon as the product of the coali- tion of three benzene nuclei, or of one naphthalene and one benzene nucleus. Additive and substitution products of phenantbrene are also known, e.g. a tetrahydride, nitro-, amino-, cyano-, and hydroxy- compounds, and sulphonic and carboxylic acids. Phenanthrol, C 14 H 9 (OH), is a hydroxy- phenanthrene, and phenanthrene- quinol, C 14 H 8 (OH) 2 , a dihydroxy-compound; when oxidized C 6 H 4 -CO the latter yields phenanthraquinone, , which may C 6 H 4 CO also be prepared directly from phenanthrene and chromic acid. It crystallizes in odourless, orange needles, melts at 200, distils unchanged, and is not volatile in steam. Phenanthra- quinone possesses the character of a diketone, reacting with hydroxylamine, sodium bisulphite, &c., but it can be reduced to the corresponding quinol by sulphurous acid. It gives a bluish-green coloration with toluene containing thio-tolene, glacial acetic acid, and sulphuric acid, and when the mixture is diluted and extracted with ether the latter becomes violet- coloured; this is the Laubenheimer reaction (B. 17, 1338). i C. Complex Hydrocarbons Fluoranthene, C 15 H 10 , pyrene, C 16 H 10 , chrysene, C 18 H 12 , retene, C 18 H 18 , and picene, C 22 H 14 , are hydrocarbons which have been isolated from that portion of coal-tar which boils above 360. Phenanthrene, pyrene, and fluoranthene are also found in "Stupp" fat, i.e. the fat obtained as a by-product from the working up of mercury ores in Idria. They all crys- tallize in white plates, sublime without decomposition, and when oxidized are converted into the corresponding ketones. Their constitution is expressed by the following formulae: C 6 H 4 .CH C 6 H 4 .CH C 10 H 6 .CH r^TT v. C 6 H 3 gCH C 10 H 6 .CH ^>C 6 H 2 .CH C 10 H 6 .CH Fluoranthene Chrysene Retene or Methyl Picene. iso-propyl phenanthrene (Cf. A. 240, 147; 284, 52; 351, 218; B. 26, 1745; B. 36, 4200.) HETEROCYCLIC COMPOUNDS 513 HETEEOCYCLIC COMPOUNDS XXXIII. INTRODUCTION The third great division of carbon derivatives consists of the Heterocydic Compounds. These, like the carbocyclic com- pounds, contain a closed chain or ring, but differ from the latter by the presence in the actual ring of atoms of elements other than carbon (cf. formulae, p. 514). The number of such compounds is enormous, although the number of elements usually associated with carbon in rings is comparatively small. The more common elements are oxygen and sulphur, but more especially nitrogen. A number of these compounds have been already mentioned; among the oxygen compounds are ethylene oxide, glycolide, phthalic anhydride, and among the nitrogen compounds suc- cinimide, phthalimide, and lactams. The compounds are divided into groups according to the number of atoms constituting the ring, thus three-membered rings, e.g. ethylene oxide; four-membered rings, e.g. betaine; five-membered rings, e.g. thiophene; six-membered rings, e.g. pyridine, &c. As in the carbocyclic series, the most important and also the most stable are the five- and six-membered rings. A further division of these groups can be made according to the number of atoms other than carbon present. Thus in the five-membered ring compounds we can have the following sub- groups: 40 + IN; 30 + 2N; 20 + 3N; termed respectively the monazole, di- and tri-azole sub-groups. The stability of the compounds and their general chemical characteristics depend to a large extent on the saturated or unsaturated nature of the rings. Compounds like thiophene, pyrrole and pyridine are stable and closely resemble ben- zene they possess general aromatic properties. Like benzene they can be reduced, the two former can each take up two or four atoms of hydrogen, and pyridine two, four or six. These reduction products no longer have aromatic properties. It is interesting to note that although the five-membered hetero- cyclic unsaturated compounds resemble benzene, the unsatu- rated carbocyclic compound cyclopentadiene does not. Some of the common heterocyclic compounds contain con- densed nuclei, i.e. the two condensed rings have two carbon atoms in common. A well-known example of condensed (9480) 2K 514 XXXIII. HETEROCYCLIC COMPOUNDS heterocyclic rings is met with in purine and its derivatives (p. 290). Examples of compounds containing a benzene nucleus condensed with a heterocyclic ring are met with in quinoline, coumarone and indole (see below). Compounds with condensed nuclei behave very differently on oxidation. Certain of them have the heterocyclic ring ruptured, and thus yield ortho-derivatives of the carbon ring; others, again, have the carbon ring ruptured, and yield ortho- acids of the heterocyclic ring. The compounds dealt with in the following sections will be grouped as follows: 1. Five-membered heterocyclic compounds containing 4C -f 10, S or N atoms, or the furane group, e.g.: CH:CH\ CH:CH CH:CH/^ CHi Furane Thiophene Pyrrole :CH\ CEL:GR\ iCH/ CH:CHX 2. Compounds formed by the condensation of these rings with a benzene nucleus, e.g.: Coumarone, Indole, j 3. Five-membered heterocyclic compounds containing three carbon atoms, e.g. pyrazole and thiazole group. 4. Six-membered heterocyclic compounds or pyridine group, e.g.: CH CH Pyridine, HC/ \N 5. The compounds formed by the condensation of a benzene and pyridine ring, e.g. : Quinoline, I I j and wo-Quinoline, 6. Six-membered heterocyclic compounds, with not more than four carbon atoms in the ring. ffURANE GROUP 515 XXXIV. FURANE GROUP CH:CH/ C CH:CH/ S CH:< Furane Thiophene Pyrrole. From these compounds a whole series of derivatives are obtained by the substitution of hydrogen by halogen, and also by the entrance of the groups 'CH 3 , CHgOH, CHO, C0 2 H, &c. In their properties furane, thiophene, and pyrrole remind one of benzene. Thiophene, in particular, is delusively like the latter, e.g. in odour and boiling-point, and its various de- rivatives often show a marvellous similarity in their chemical and physical relations to the corresponding derivatives of benzene. Furane, pyrrole, and thiophene also resemble one another in many respects. All three boil at relatively low temperatures ( -f- 32, 131, 84), are either insoluble or only sparingly soluble in water, but readily in alcohol and ether, and show many an- alogous colour reactions. Thus pyrrole and thiophene and their derivatives give, for the most part, an intense violet to blue coloration when mixed with isatin and concentrated sulphuric acid, and a cherry-red or violet coloration with phenanthra- quinone and glacial acetic or sulphuric acid. The vapour of pyrrole colours a pine shaving which has been moistened with hydrochloric acid carmine red (irvppos, fiery-red), while furalde- hyde vapour colours it an emerald green; the latter likewise colours a piece of paper moistened with xylidine- or aniline- acetate red. Furane is converted by mineral acids, e.g. hydro- chloric acid, into an insoluble amorphous powder, and pyrrole into an insoluble amorphous brown-red powder, " pyrrole-red " (with evolution of ammonia), while thiophene remains unal- tered; the derivatives show a similar behaviour. Pyrrole is distinguished from the two other compounds by having feebly basic properties. Derivatives of all three compounds may be obtained from mucic acid, C0 2 H (CH OH) 4 C0 2 H (p. 259). When distilled, mucic acid yields pyromucic acid or furane-a-carboxylic acid; when its ammonium salt is distilled, pyrrole is formed; and when free mucic acid is heated with barium sulphide, thiophene a-carboxylic acid is obtained, e.g. : CH.:(OH):.CiHi ;;(OH)I.:COO:H CH:CH . = C0 2 +3H 2 0+ 1 >0. 3iIi;(0 : .H).i COOH CH:C(C0 2 H)/ 516 XXXIV. FURANE GROUP A very general method for the formation of derivatives of this group is from y-diketones, e.g. acetonyl-acetone, CH 3 CO CH 2 .CH 2 .CO.CH 3 (p. 221; also p. 230). When this com- pound is heated with phosphorus pentoxide or zinc chloride, dimethyl -furane is formed; with phosphorus pentasulphide, dimethyl-thiophene; with alcoholic ammonia, dimethyl-pyrrole (B. 18, 58, 367; 20, 1074). This behaviour would indicate that the acetonyl- acetone reacts as the tautomeric compound: m,C(OH):CH.CH:C(OH).CH a or upon this assumption the formation of dimethyl-furane appears simply as that of an anhydride, that of dimethyl-pyrrole as an exchange of 2 (OH) for NH (imide formation), and that of di- methyl-thiophene as the formation of a sulphide, i.e. exchange of 2(OH) for S, according to the following equations : H CH:C(CH 3 K H " CH:C(CH 3 )/ CH:C(CH3>OH CH:C(CH 3 )\ T " H CH:C(CH r H CH:C(CH From the above reactions the constitutional formula for the three compounds would be: Furane Thiophene Pyrrole CH:CHv CH:CHv ^ CH:CBX CH:CH/ CH: (ft) W 03) (a) 03) (a) These formulae receive corroboration from the frequently ob- served fact that the substances are capable of yielding additive compounds with bromine or hydrogen (see Pyrroline). Ac- cording to the above formulae, two isomeric mono-substituted derivatives of furane and thiophene are possible: (1) one in which the hydrogen atom (a) which stands nearest to the oxygen, sulphur, or nitrogen atom, and (2) one in which a quasi-middle hydrogen atom (ft) is substituted. AM a matter FtTRANE. FUROL 517 of fact, two such isomers have been observed in many cases, e.g. two thiophenic acids. These form mixed crystals, the crystals having a homogeneous appearance although they con- tain both acids (V. Meyer, A. 236, 200). In the case of pyrrole, on the other hand, three kinds of derivatives (a-, /?-, and n-) are both possible and known. An examination of the molecular refraction of thiophene and also of its heat of combustion (B. 1885, 18, 1832) point to the presence of only one double bond in the thiophene mole- PTT PTT\ cule. The formula J>S has been suggested, and this CH CH/ is quite in harmony with the production of substituted maleic acids by the oxidation of thiophene derivatives. Probably the simplest explanation is that the thiophene molecule contains centric bonds, and should be represented as: Furane or furfurane is a colourless mobile liquid, boiling at 32, and with an odour resembling that of chloroform. It is present in pine-wood tar, in the first runnings from ordinary wood tar, &c., and is obtained by the distillation of sugar with lime, or by distilling barium pyromucate. a-Methyl-furane or sylvane is likewise present in pine-wood tar, and in the pro- ducts of distillation of sugar with lime. It boils at 65. aa- Dimethyl-furane is obtained from sugar and lime, and also from acetonyl-acetone (p. 516). It is a colourless mobile liquid of a characteristic odour, and boils at 94. Concentrated acids convert it into a resin; it can be transformed back into acetonyl-acetone. Furol, a-furaldehyde or furfuraldehyde, C 4 H 3 0CHO (Dobe- reiner), is obtained when pentoses, e.g. arabinose and xylose, are distilled with concentrated hydrochloric acid: C 6 H 10 6 - 3H 2 = C 6 H 4 2 . The yield is quantitative, and the method is made use of foi determining the amounts of pentoses present in various sub- stances. It may also be obtained by distilling bran, wood, sugar, or various carbohydrates with moderately concentrated sulphuric 618 XXXIV. FURANE GROUP acid. It is a colourless oil of agreeable odour, turns brown in the air, and boils at 162. It possesses all the properties of an aldehyde, and can yield condensation products in much the same manner as benzalde- hyde (p. 424): e.g. furom, C 4 H 3 O.CH(OH).(X).C 4 H 2 0, corre- sponding with benzoin; furalmalonic acid, C 4 H 3 0-CH:C (C0 2 H) 2 , corresponding with benzalmalonic acid; and furyl- acrylic and aZfo-furylacrylic acid, C 4 H 3 CH : CH C0 2 H, corresponding with cinnamic and a/fo-cinnamic acids. Pyromucie acid, C 4 H 3 0-C0 2 H. Furane-a-carboxylic acid crystallizes in needles or plates similar to those of benzoic acid, and melts at 132; it sublimes easily, is readily soluble in hot water and alcohol, and decolorizes alkaline permangan- ate almost instantaneously. Pyrrole is a constituent of coal-tar (Runge) and of bone-oi 1 (Anderson); it boils at 131, and possesses, like many of its homologues, a chloroform odour. It is a secondary base, and its imino-hydrogen is replaceable by metals and alkyl, or acyl radicals. In addition to the methods of formation mentioned on p. 516, it may also be obtained v by heating succinimide (p. 239) with zinc dust, or from acetylene and ammonia at a red heat. When pyrrole is acted upon by hydroxylamine the ring is CH 2 .CH:N.OH broken, and the dioxime of succmic-aldehyde, , CH 2 CH : N OH is formed; this yields tetramethylene-diamine upon reduction (R 22, 1968). Dimethyl-pyrrole in a similar manner yields acetonyl-acetone-dioxime. w-Potassium-pyrrole, C 4 H 4 NK, which is obtained from pyr- role and potassium or solid potassic hydroxide, is a colourless compound which is decomposed by water. A number of w-alkyl and acyl derivatives may be prepared by the aid of this potassium compound, but most of them are relatively unstable, and when heated are transformed into the isomeric a-alkyl or acyl compounds. A most interesting reaction is the conversion of pyrrole into pyridine (p. 533) by means of sodium methoxide and chloroform or methylene iodide. By the action of iodine and alkali, substitution takes place with the forma- tion of tetra-iodo-pyrrole or iodole, C 4 I 4 (NH), which crystal- lizes in yellow plates, and is used as an antiseptic in place of iodoform. Zinc and glacial acetic acid convert pyrrole into pyrroline, tHIOPHENE 619 34, 3954), a colourless liquid boiling at 91 and also a strong secondary base; when this latter is heated with hydriodic r^TT OTT acid, it is further reduced to pyrrolidine, 2 yNH, a CH 2 CH 2 / colourless, strongly alkaline base resembling piperidine, and boiling at 86. It is also formed by the action of sodium on an alcoholic solution of succinimide, and is obtained synthetic- ally by heating S-chloro-butylamine with alkali, and by treating ethylene cyanide with sodium and alcohol, thus : CH 2 .CN CH 2 .CH 2 .NH 2 C CH 2 .CN 4 CH 2 .CH 2 .NH 2 ' = CH 2 .CH/ N it is consequently designated tetramethylene-imine (Ladenburg, B. 19, 782; 20, 442). The red colouring matter of blood yields pyrrole derivatives as some of its products of decomposition, and pyrrolidine derivatives, especially pyrrolidine -carboxy lie acid (proline), are decomposition products of albumen. Thiophene (V. Meyer, B. 16, 1465, &c.) is present in coal- tar, being invariably found in benzene (up to 0*5 per cent); the same applies to its homologues thiotolene (methyl-thio- phene), and thioxene (dimethyl-thiophene), which accompany toluene and xylene, &c. Its boiling-point (84) is almost the same as that of benzene (80 - 4), from which it is extracted by repeatedly shaking with small quantities of concentrated sul- phuric acid, which transforms the thiophene into a soluble sulphonic acid (B. 17, 2641, 2852). It is also attacked more readily than benzene by other reagents, such as halogens. Thiophene is also obtained synthetically by leading the vapour of ethyl sulphide through a red-hot tube (Kekutt), and in small quantity by heating crotonic acid, w-butyric acid, paraldehyde, &c., with phosphorus pentasulphide. Stilbene (p. 478) and sulphur yield tetraphenyltMophene, thionessal, m.-pt. 183. The preparation and properties of the thiophene derivatives are almost identical with those of the corresponding benzene compounds. Thus nitric acid acts on thiophene to produce a nitro-thiophene, analogous to nitro-benzene, which can in its turn be reduced to amino-thiophene; the latter is, how- ever, much less stable than the corresponding ammo-benzene. 620 XXXV. CONDENSED BENZENE, FURANE, ETC. RINGS The boiling-points of thiophene compounds and their corre- sponding benzene derivatives are almost identical. The homologues can be obtained by Fittig's synthesis, the a-compounds from 1 : 4-diketones, and the /^-derivatives from mono- or di-substituted succinic acids and phosphorus penta- sulphide. Thiophene-sulphonic acid, OHS0 2 C 4 H 3 S, decomposes into thiophene and sulphuric acid when superheated with water, and does not yield a phenol on fusion with potash. Hydroxythiotolene, C 4 H 2 S(CH 3 )(OH), the phenol of thiotol- ene, is formed by heating Isevulic acid with P 2 S 5 (B. 19, 553). A mixture of the a- and /3-monocarboxylic acids when crystallized slowly from water yields mixed crystals, which cannot be resolved into their components. The blue coloration which is formed when benzene contain- ing thiophene is shaken with isatin and concentrated sulphuric acid, is due to the formation of the blue colouring matter "Indophenin", C^ONS. (Of. V. Meyer's "Die Thiophengruppe", Braunschweig, 1888.) XXXV. COMPOUNDS FORMED BY THE CONDEN- SATION OF A BENZENE NUCLEUS WITH A FURANE, THIOPHENE, OR PYRROLE RING NH Coumarone Benzo-thiophene Indole. Coumarone closely resembles pseudo-cumene. It occurs in coal-tar, and may be isolated as its picrate. It is usually obtained from bromocoumarin; this with alcoholic potash yields coumarilic acid which gives coumarone when distilled with lime: It is a colourless liquid distilling at 170; yields a dibromide and a dihydro-derivative, thus indicating the presence of a double bond. Numerous derivatives are known. INDOLE 621 Benzo-tkiopkene, Thionaphthene, melts at 31, boils at 221, and has an odour resembling naphthalene. INDOLE GROUP Indole (Baeyer, 1868) is the most important compound in this group, as it is the parent substance of indigo. As a derivative of pyrrole it possesses feebly basic properties. It is obtained by distilling oxindole with zinc dust; by heating o-nitro-cinnamic acid with potash and iron filings; by the action of sodic ethoxide upon o-amino-/?-chloro-styrene (B. 17, 1067): C6H4<^ : a CHC1 + NaO.C 2 H 5 = OJEL^^^CH. + NaCl + C 2 H S OH; by the pancreatic fermentation of albumen; together with skatole by fusing albumen with potash; and by passing the vapours of various anilines, e.g. diethyl-o-toluidine, through red-hot tubes, &c. It occurs in the essential oil of jasmine flowers, crystallizes in plates, melts at 52, volatilizes readily with steam, and usually has a peculiar faecal -like odour, although in the pure state and diluted it is stated to have a fragrant odour. It is feebly basic, colours a pine shaving which has been moistened with hydrochloric acid cherry-red, with nitrous acid gives a red precipitate, which consists partly of the so-called nitroso-indole, [C 8 H 6 N(NO)] 2 (a delicate re- action; see B. 22, 1976), and yields acetyl-indole when acety- lated. These last reactions show that indole contains an imino- group. When oxidized with ozone it yields indigo. The system of numbering the substituents in the indole molecule is as follows: The 1 -substituted derivatives are sometimes termed w-de- rivatives, e.g. %-methyl-indole, C 6 H 4 <^pTT_^CH. Various derivatives may be obtained synthetically by the condensation of the aromatic primary or secondary hydrazines either with pyroracemic acid or with certain ketones or alde- hydes, and treatment of the resulting hydrazones with dilute hydrochloric acid or zinc chloride, when ammonia is eliminated 622 XXXV. CONDENSED BENZENE, FURANE, ETC. RINGS (E. Fischer, A. 236, 116: 242, 372); thus acetone -phenyl- PIT hydrazone, C 6 H 5 . NH . N : O^g 3 , yields a- methyl -indole, CH 3 , propaldehyde - phenyl - bydrazone yields skatole, and phenacyl bromide and aniline yield a-phenyl- indole. See also B. 25, 2860. Skatole, 3-methyl-indok, C 6 H 4 <^Q^ e ~^>CH, is found in faeces, and is produced, together with indole, e.g., by the decay of albumen, or by fusing it with potash. It crystallizes in colour- less plates of a strong faecal odour and melts at 95. Nitrous acid does not colour it red. It takes up two atoms of hydrogen to form a hydro-compound. Acids, aldehydes, &c., are also known. Dioxindole, C fi H 4 <^ QH ^>CO, or the lactam of o-amino mandelic acid, NH 2 .C 6 H 4 .CH(OH).C0 2 H, is obtained by the reduction of isatin (into which it is again easily oxidized) with zinc dust and hydrochloric acid, or by the oxidation of oxin- dole. It crystallizes in colourless prisms, melts at 180, and possesses both basic and acid properties (two hydrogen atoms being replaceable); it also forms a nitroso- compound, an N-acetyl derivative, &c. Oxindole, C 6 H 4 <^QTT ^>CO, the lactam of o-amino-phenyl- acetic acid, is formed by the reduction of 0-nitro-phenyl-acetic acid (p. 452); also by that of dioxindole with tin and hydro- chloric acid. It crystallizes in colourless needles, melts at 1 20, is readily oxidized to dioxindole, and therefore possesses feebly reducing properties. Oxindole is amphoteric, dissolving both in alkalis and in hydrochloric acid. Baryta water at a some- what high temperature transforms it into barium 0-amino- phenyl-acetate. The imino-hydrogen is exchangeable for ethyl, acetyl, the nitroso-group, &c. Isomeric with oxindole is indoxyl, CgHi^Vr ^CH, which is obtained by the elimination of carbon dioxide from indoxylic acid, a product formed from phenyl-glycocoll (p. 452), also by fusing indigo with potash. It is often present in the urine of the carnivora as potassium indoxyl-sulphate or urine-indican, C 8 H 6 N-0.(S0 3 K). It forms yellow crystals, melting at 85, is moderately soluble in water with yellow fluorescence, and iSATiN 523 not volatile with steam. It is very unstable, quickly becoming resinous, and is readily transformed into indigo when its alka- line solution is exposed to the air, or when ferric chloride is added to its solution in hydrochloric acid. It yields a nitroso- compound, C 6 H 4 <Qy'QjTw>CH, of the same character as the nitrosamines, and therefore it contains an imino-group; further, its relation to indoxyl-sulphuric acid shows that it contains an alcoholic hydroxy-group, and thus its constitution follows. Potassium indoxyl-sulphate is prepared synthetically by warming indoxyl with potassium pyrosulphate; it crystallizes in glistening plates and is hydrolysed when warmed with acids. Ethyl-indoxyl is obtained from indoxyl by the exchange of the hydroxylic hydrogen for C 2 H 5 . Derivatives of the hypo- thetical pseudo- indoxyl, C 6 H 4 <^QQj>CH 2 , are also known, some of them being convertible into indigo derivatives (e.g. diethyl-indigo). Indoxylic acid, C6 H 4^^ C0 2 H, the carboxylic acid of indoxyl, forms white crystals, is oxidized to indigo by ferric chloride, and breaks up into indoxyl and carbon dioxide when fused. It is obtained from its ester, ethyl indoxylate, by fusing with soda. The latter compound crystallizes in stout prisms, melts at 120, and may be obtained, among other methods, by the reduction of ethyl o-nitro-phenyl-propiolate with ammonium sulphide. PO Isatin, C 6 H 4 <^TT^>CO, the lactam of o-aminp-benzoyl-formic acid (p. 463), is readily prepared by oxidizing indigo or in- doxyl with nitric acid (Erdmann and Laurent, 1841 ; cf. also B. 17, 976). It may also be obtained by the oxidation of dioxindole or of oxindole (indirectly). The following are among some of the most important methods by means of which isatin has been synthesised: (a) When o-nitro-phenyl-glyoxylic acid (o-nitro-benzoyl- formic acid, p. 462) is reduced, the corresponding amino-acid is obtained; but this immediately loses water, yielding a lactam or lactim : mi 524 XXXV. CONDENSED BENZENE, FtTRANE, ETC. RINGS (b) 0-Nitro-phenylacetic acid when reduced yields the lactam, oxindole, C fi H 4 <^ XT T/^>CO, and this with nitrous acid M.Mxi-^ P/"NT OT^ gives the iso-nitroso-oxindole, 6 H 4 <i&T_ ; >CO, which on reduction is converted into amino-oxindole, and this on oxidation with ferric chloride yields isatin. (c) Sandmeyer has worked out the following synthesis: Aniline and carbon disulphide readily yield thio-carbanilide, CS(NHC 6 H 5 } 2 , which, on boiling with potassium cyanide, white-lead, and water, yields hydrocyano-carbo-diphenyl- imide, C 6 H 5 N:C(CN).NHC 6 H 5 . With ammonium sulphide this latter yields ^\ C |>C.NHC 6 H 5 , which is con- verted by concentrated sulphuric acid into a-isatin-anilide, C 6 H 4 <^jr ^C'NHC 6 H 5 , and this may be hydrolysed by dilute acids to isatin and aniline (C.C. 1900, 2, 928). (d) 0-Nitrophenyl-propiolic acid (p. 456) may be synthesised, and when this is warmed with alkalis it undergoes molecular rearrangement and yields isatogenic acid, which by elimi- nation of carbon dioxide forms isatin: Isatin crystallizes in reddish-yellow monoclinic prisms, which are only sparingly soluble in cold water, but more readily in hot water and in alcohol to a brownish-red solution. It dis- solves in potassium hydroxide solution, yielding the potassium derivative, C 6 H 4 <^ = ^>COK, which is readily hydrolysed to potassium 0-amino-phenyl-glyoxylate when boiled with water. /~^{~\ Isatin chloride, C 6 H 4 <^;^C.C1, is obtained when isatin is heated with phosphorus pentachloride, and on reduction with zinc dust and acetic acid yields indigo. Two isomeric methyl ethers are known : and O-methyl isatin N-methyl isatin or pseudo-methyl isatin. The O-ether is obtained by converting the potassic-isatin into the silver compound, and then heating this with methyl INDIGO 525 iodiae. It is a colourless solid melting at 102, and on hydrolysis yields isatin or o-amino-phenyl-glyoxylic acid. The N-ether may be obtained by the action of sodic hypo- bromite on N-methyl-indole. Its constitution follows from its method of formation, and also from the fact that on hydrolysis it yields o - methyl amino - phenyl- glyoxy lie acid, T /CO.CO 2 H The constitution of isatin itself for some years was a matter of dispute; from its method of formation it must be either the lactam or lactim of o-amino-phenyl-glyoxylic acid. Certain of its methods of formation and of its reactions, e.g. with alkalis or phosphorus pentachloride, point to the lactim for- mula, whereas others would indicate the lactam constitution isatin is thus a typical tautomeric compound. Hartley and Dobbie (J. C. S. 1899, 647) assign to it the lactam constitution. The ultra-violet absorption of alcoholic solutions of isatin is almost identical with that of the N-methyl ether, and quite different from that of the 0-methyl ether, and hence the N-methyl ether and the parent substance have similar formulae. Isatin is thus a pseudo-acid, since the hydrogen compound itself is the ketonic substance, C 6 H 4 <^p,Q^>COj but its sodic derivative is the enolic compound, INDIGO AND RELATED COMPOUNDS Indole or benzo-pyrrole Indoxyl or hydroxy-indole Oxindole or o-amino-phenyl-aceticl n -rr /OH acid lactam .......... . ..... ' .......... / C H 4\NB Dioxindole or o - amino - mandelic acid lactam Isatin or o-amino-phenyl-glyoxylicl ~ ,-,. / CO \nr& acid lactam ..... _...L:......:..../ C H *\NH/ Indigo ..................................... C 6 H 4 <^>C:C<^>C 6 H 4 . Indigo, which is obtained from the indigo plant (Indigofera tinctoria), and from woad (Isatis tindoria), has been known for thousands of years as a valuable blue dye, especially for woollen fabrics. In addition to indigo -blue (indigotin), 526 XXXV. CONDENSED BENZENE, FURANE, ETC. RINGS commercial indigo contains indigo-gelatine, indigo-brown, and indigo-red, all of which can be extracted from it by solvents. The colouring matter is not present as such in the indigo plant, but as the glucoside of indoxyl " Indican ", from which it can be prepared either by dilute acids or certain enzymes and sub- sequent oxidation with atmospheric oxygen. It forms a dark-blue coppery and shimmering powder or, after sublimation, copper-red prisms, insoluble in most solvents (including the alkalis and dilute acids), but dissolving to a blue solution in hot aniline and to a red one in paraffin, from either of which it may be crystallized. Its vapour is dark-red. The formula C 16 H 10 2 N 2 is confirmed by its vapour density. It is converted by reducing agents, such as ferrous sulphate and caustic soda solution or grape-sugar and soda, into the leuco-compound, indigo-white, C 16 H 12 2 N 2 , a white crystalline powder soluble in alcohol and ether, also in alkalis (as a phenol); the alkaline solution quickly becomes oxidized by the oxygen of the air, with the separation of a blue film of indigo. It yields an acetyl compound which crystallizes in colourless needles. Warm concentrated or fuming sulphuric acid dissolves indigo to indigo -monosulphonic and disulphonic acids, the former of which (termed phoenicin-sulphonic acid) is sparingly soluble in water, but the latter readily so; the sodium di- sulphonate is the indigo-carmine of commerce. Nitric acid oxidizes indigo to isatin, while distillation with potash yields aniline, and heating with manganese dioxide and a solution of potash, anthranilic acid. Indigo has been prepared synthetically by numerous methods. The following are among the most important: 1. By the reduction of isatin chloride with zinc dust and acetic acid: The syntheses of isatin already described (pp. 523 and 554) are thus syntheses of indigo. 2. By warming o-nitro-phenyl-propiolic acid with grape-sugar in alkaline solution (Baeyer, 1880): 2N0 2 .C 6 H 4 C:C.C0 2 H + 4H = C 1G H 10 N 2 O 2 + 2CO 2 + 2H 2 O. 3. Baeyer and Drewson (1882) started with toluene, and on nitration obtained a mixture of o- and j?-mtro-toluenes, The INDIGO 527 0-compound was oxidized by manganese dioxide and sulphuric acid to 0-nitro-benzaldehyde, and this was then condensed with acetone, yielding o-nitro-phenyl-lactyl methyl ketone, NO 2 C 6 H 4 CH(OH) CH 2 . CO CH 3 ; which when warmed with alkalis gave indigo and water. The yield was good, but the method was of no great practical importance, as the amount of toluene is limited, and no use could be found for the ^?-nitro-toluene obtained as a by-pro- duct. 4. In 1890 Neumann obtained phenyl-glycocoll by the condensation of aniline with chloracetic acid: C 6 H 5 .NH.CH 2 .CO 2 H, and when this was fused with alkali, indigo-white was obtained. A modified form of Heumann's synthesis consists in con- densing anthranilic acid (p. 452) with chloracetic acid, when phenyl-glycocoll-o-carboxylic acid is obtained, and this on fusion with alkali yields indoxyl, which oxidizes in the air to indigo-blue. The yield is good, and this method is now employed on a manufacturing scale by the "Badische Anilin Fabrik" for the production of artificial indigo, as anthranilic acid can be obtained cheaply; the general method being the oxidation of naphthalene by mercury and sulphuric acid to phthalic acid, the conversion of this into phthalic anhydride, and then into phthalimide by the aid of ammonia. The phthalimide with alkali and chlorine yields anthranilic acid o-amino-benzoic acid (Hofmann reaction, p. 184). Homologues of indigo are produced in an analogous manner, and its sulpho-acids by the action of fuming sulphuric acid upon phenyl-glycocoll. Indigo-blue is one of the best of the blue dyes, on account of its " fastness " to light, alkalis, acids, and soaps. As indigo- blue itself is insoluble, its " leuco " compound indigo-white is usually employed, the fabric being immersed in an alkaline solution of this, and then exposed to the air, when oxidation to indigo-blue takes place. Indigo-blue is usually reduced to indigo-white by means of calcium hyposulphite. The indigo- white is a colourless solid with phenolic properties, and probably has the constitution represented by the formula 528 XXXVI. PYRAZOLE GROUP Iiidirubin, Indigo-purpurin, is an isomeride of indigo-blue, and can be obtained synthetically by the condensation of isatin and indoxyl in alkaline alcoholic solution: It is also obtained, together with indigo-blue, by the reduc- tion of isatin chloride. It crystallizes from aniline in chocolate- brown needles, and on oxidation yields isatin. (For history and manufacture of indigo, see /. Ind. 1901, 239, 332, 551, 802; J. C. S. 1905, 974.) XXXVI. PYKAZOLE GROUP, ETC. 1. PYRAZOLE GROUP This comprises compounds with a five-membered ring contain- ing three carbon and two nitrogen, sulphur, or oxygen atoms. Pyrazole, aCH-N-v 2 >NH, *CH:< 5 is theoretically derivable from pyrrole in the same way aa pyridine is from benzene, i.e. by the exchange of CH for N. The positions three and five appear to be identical unless the H of the NH is replaced by alkyl groups. It is a weak base of great stability, crystallizing in colour- less needles; it melts at 70, boils at 185, and possesses aro- matic properties (B. 1895, 28, 714). Its simplest synthesis is by the union of acetylene and diazo-methane: HO CHf HC:CH (Van, Pechmann, B. 1897, 31, 2950). (For other syntheses, see B. 23, 1103; A. 273, 214.) Pyrazoline, C 3 H 6 N 2 , and pyrazolidine, CgHgNg, are derived theoretically from pyrazole by the addition of hydrogen. By the exchange of two atoms of hydrogen for one. of oxygen, the formula of pyrazole changes into that of pyrazolone, CH : THIAZOLE 529 (an oil, b.-pt. 77; see B, 25, 3441), and by the entrance of phenyl and methyl into this latter we get: l-Phenyl-3-methyl-pyrazolone, which is obtained by the action of phenylhydrazine on ethyl acetoacetate (p. 230): CH,.CO H 2 N CH S .C:N CH,COOEt + NHPh= This crystallizes in compact prisms, melts at 127, and boils without decomposition. As a weak base it dissolves in acids, and is also soluble in alkalis; it further contains the chemi- cally-active methylene group. When it is heated with methyl iodide and methyl alcohol it yields : l-Phenyl-2:3-dimethyl-pyrazolone or antipyrine, C n H 12 N 2 O, which is also produced by the action of ethyl acetoacetate upon methyl-phenyl-hydrazine, and which therefore possesses the constitutional formula (L. Knorr, A. 238, 137), CMe-NMex L : ., cH_co> ph - (^ It crystallizes in small colourless plates melting at 113. The aqueous solution is coloured red by ferric chloride and blue- green by nitrous acid. Antipyrine is an excellent febrifuge. /3-Ketonic acids, /?-ketonic aldehydes, /3-diketones also yield pyrazole derivatives with phenyl-hydrazine. Isomeric with pyrazole is glyoxaline (p. 530), in which the two atoms of N are separated by a C atom. 2. THIAZOLE GEOUP Thiazole, is derived from thiophene in the same way as pyridine is from benzene, by the exchange of CH for N, and closely resembles along with its derivatives the bases of the pyridine series in properties. It is obtained from amino-thiazole (see below) by the exchange of the amino-group for hydrogen, in a similar manner to the conversion of aniline into benzene. It is a colourless liquid, boiling at 117, hardly distinguishable from pyridine; as a base it forms salts, but it is scarcely affected by concentrated sulphuric acid, &c. (Hantzsch, Popp, A. 250, 273). (B480) 2L 530 XXXVI. PYRAZOLE GROUP Amino-tMazole, is formed by the action of mono-chloraldehyde upon thio-urea (pseudo form), thus: The constitution of the thiazoles follows from this and similar modes of formation. Amino-thiazole is a base of perfect " aromatic " character, like that of aniline. (Cf. Rantzsch and his pupils, A. 249, 1, 7, 31; 250, 257; 265, 108.) As further types of five-membered rings, may be cited : CH.N Imidazole or glyoxalin Oxazole, which are related to thiazole as pyrrole and furane are tc thiophene. Triazole, NH, and tetrazole, are examples of five-membered rings extremely rich in nitro- gen. (Cf. B. 25, 225, 1411; 26, 2392.) The foregoing constitutional formula with their double linkings correspond with KekuU's benzene formula. But for- mulse with diagonal (centric) linkings analogous to the centric benzene formula (p. 334) have been introduced recently. (Cf. Bamberger, B. 24, 1758; A. 273, 373; also A. 249, 1; 262, 265; B. 21, Ref. 888; 24, 3485; 27, 3077; 28, 1501.) XXXVII. SIX-MEMBERED HETEROCYCLIC RINGS Ring compounds closely related to pyrrole, thiophene, and furane, but containing six atoms in the ring (viz. five carbon atoms + ne x yg en > sulphur, or nitrogen atom), are known. The representatives of these are : 8 - valerolactone, glutaric anhydride, y-PYRONE 531 (p. 240), and more especially the pyrones, e.t\ y-pyrone, Of the nitrogen compounds, pyridine, and piperidine, CH 2 <^QTT 2 "pTT 2 ^>NH, are of great importance. The derivatives of the sulphur compound, penthiophene, ^^CH'CHX^' are ^ ^ ut ^^ e i m P rtance - Six-membered rings containing two nitrogen atoms are the diazines, C 4 H 4 N 2 , the ortho compound is.pyjidazine, the meta pyrimidine, and the para pyrazine. The compound, is morpholin. Six-membered rings con- fining three and four nitrogen atoms are termed respectively triazines and tetrazines. (Of. triazole and tetrazole, p. 530.) A. Pyrones y-Pyrone, a solid, m.-pt. 32-5 and b.-pt. 315, is ob- tained when its dicarboxylic acid, chelidonic acid (p. 533), is heated, aa-dimethyl-y-pyrone, C0< ! ^' may be syn " thesised from cupric ethyl aceto-acetate and carbonyl chloride. (C0 2 Et).CO.CH 3 p Uu CH(C0 2 Et).CO.CH On hydrolysis with sulphuric acid the ester yields the free acid, which loses carbon dioxide, yielding: CO.CH S or xCH:C(OH)C which immediately loses water, yielding dimethyl-y-pyrone : (For a modified formula, see Collie, J. C. S. 1904, 971.) Collie and Tidde (J. C. S. 1899, 710) have shown that this com- pound can form definite salts with acids, e.g. the hydrochloride, C 7 H 8 O 2 , HC1, and oxalate. The addition of the acid un- doubtedly occurs at the oxygen atom, since the salts are relatively unstable and are completely hydrolysed in dilute aqueous solution. The oxygen atom in these salts, therefore, 532 XXXVII. SIX-MEMBERED HETEROCYCLIC RINGS probably functionates as a tetravalent atom, [oXKci 1 and the salts are termed oxonium salts on account of their simi- larity to ammonium salts. Numerous other compounds have since been obtained, which tend to show that the oxygen atom can frequently functionate in this manner, e.g. numerous oxygen compounds, esters, ethers, ketones, acids, aldehydes yield definite crystalline compounds with anhydrous metallic salts, e.g. MgBr 2 or A1C1 8 (Walker, J. C. S. 1904, 1106; similar oxygen compounds also form well-defined crystalline salts with complex acids, e.g. ferrocyanic acid (Baeyer and Villiger, B. 1901, 34, 2679, 3612; 1902, 35, 1201); and lastly, the addi- tive compound of organo-magnesium derivatives with ether are probably of the type, c*ip>0<f gCHs . Solutions of the oxonium salts have exactly the properties we should expect. Since the salt is derived from a very feeble base (solutions of dimethyl-pyrone are very feeble conductors) and a rela- tively strong acid, the solution should be highly hydrolysed, and should give a strongly acid reaction. That the hy- drolysis is not complete in the case of a moderately con- centrated solution of the picrate has been shown by WHlden (B. 1901, 34, 4191), who compared the partition coefficient of picric acid between water and benzene both with and without the addition of dimethyl-pyrone, and found that the ratio concentration of benzene solution ^ less when ^ is concentration of aqueous solution present. Other methods which have also led to the conclusion that a certain amount of salt exists in solution are (a) depression of the freezing-point of aqueous solutions. If no compound exists in an aqueous hydrochloric acid solution, then the depression caused would be the sum of the depressions produced by the known amounts of dimethyl-pyrone and hydrochloric acid present. The actual value obtained is less than this sum (Walderi). (b) A determination of the electrical conductivity. If no compound is formed, the conductivity should be the same as the conductivity of a solution of pure hydrochloric acid of the same concentration; but if any appreciable amount of a salt is formed in solution this will give rise to a certain number of C r H 8 O 2 H and Cl, i.e. the number of hydrions will be less than in a solution of pure hydrochloric acid of the same PYRIDINE 533 concentration, and hence the electrical conductivity will be considerably reduced. It has actually been found that the conductivity is less, and that it tends to decrease as the solution becomes more concentrated. y-Pyrone-dicarboxylic acid, or chelidonic acid, occurs in the greater celandine (Chelidonium majvs), and may be synthesised by Claisen's method (p. 224). Acetone and ethyl oxalate readily condense, yielding the ester of acetone-dioxalic acid or xantho- chelidonic acid : XCH 3 , C0 2 Et-C0 2 Et _ m /CH:C(C0 2 Et)OH C0 2 Et . C0 2 Et - CU \CH : C(CO 2 Et)OH which immediately loses water, yielding ethyl chelidonate, and this on careful hydrolysis yields chelidonic acid : The salts of this acid are colourless, but when it is warmed with an excess of alkali yellow salts of xantho-chelidonic acid are formed, thus indicating the readiness with which the ring is ruptured. B. Pyridine Pyridine, C 5 H 5 N, may be compared with benzene in many points : 1. It is even more stable than benzene, and does not yield substituted derivatives so readily with such reagents as sul- phuric and nitric acids or the halogens. Sulphonic acids are obtained at very high temperatures only; nitro-pyridines are as yet unknown, as are also iodo-pyridines ; while chloro- and bromo-pyridines have so far only been prepared in small num- ber. Neither pyridine nor its carboxylic acids are affected by nitric acid, chromic acid, or permanganate of potash. 2. The behaviour of its derivatives is on the whole very like that of the derivatives of benzene. Thus its homologues (and also quinoline, &c.) are transformed into pyridine-carboxylic acids when oxidized, and these acids yield pyridine when dis- tilled with lime, just as benzoic acid yields benzene. 3. The isomeric relations are also precisely analogous to those of the benzene derivatives. Thus the number of the isomeric mono-derivatives of pyridine is the same as that of the isomeric bi-derivatives of benzene, viz., three; and the number of the bi-derivatives of pyridine, containing the same substituents, the same as that of the benzene derivatives C 6 H 3 XXX', viz., six. 534 XXXVII. SIX-MEMBERED HETEROCYCLIC RINGS 4. Just as two benzene nuclei can form naphthalene, so can a benzene and a pyridine form the compound quinoline : N. 5. The products of reduction are likewise analogous. Pyri- dine like benzene yields a hexahydro-derivative, C 5 H n N, only somewhat more readily; this is known as piperidine. Quino- line yields a tetrahydro-derivative, C 9 H n N, more readily than naphthalene, and acridine readily yields a dihydro-derivative, C 13 H n N", which is analogous to anthracene dihydride. In these latter compounds further combination with hydrogen may take place, but there is likewise a tendency to the reproduction of the original bases. We are therefore forced to the conclusion that pyridine has a ring constitution similar to that of benzene, and is to be represented as: CH CH HC CH HC ^& N N In contradistinction to the neutral benzene hydrocarbons, pyridine and its homologues are strong bases, most of them having a pungent odour; pyridine is readily soluble in water, but quinoline only slightly so. They distil or sublime with- out decomposition, and form salts; those with hydrochloric and sulphuric acids are for the most part readily soluble, while those with chromic acid or hydro -ferrocyanic acid, though often characteristic, are usually only sparingly soluble ; they also form double salts with the chlorides of platinum, gold, and mercury, most of which are sparingly soluble, e.g. (C 5 H 5 N) 2 H 2 PtCl 6 . The bases are tertiary, and hence cannot be acetylated; they combine, however, with alkyl iodides, yielding quater- nary ammonium salts, e.g. pyridine and methyl iodide yield C 5 H 5 N, CH 3 I, methyl-pyridonium iodide. Pyridine and some of its homologues are present in coal-tar, and are therefore constituents of the lower boiling fractions. They may be extracted from these by shaking with dilute SYNTHESES OF PYRIDINE DERIVATIVES 535 sulphuric acid, in which they dissolve. It is also present in tobacco smoke. A number of pyridine bases are present in bone-oil or Dippel's oil, a product obtained by fee dry distil- lation of bones from which the fat has not been extracted. Mixtures of pyridine bases can readily be obtained from this source. Certain alkaloids 4Hfc^ 7) yield pyridine or its derivatives when distilled alone^r with alkalis, e.g. chincho- nine when distilled with potash yields a dimethyl-pyridine or lutidine. Pure pyridine may be obtained by distilling its carboxylic acid with lime. Among the more interesting methods by means of which pyridine and its derivatives have been synthesised are the following : 1. When pentamethylene-diamine hydrochloride is strongly heated it yields piperidine, and when this is oxidized with concentrated sulphuric acid at 300 pyridine is formed (Laden- burg): CH 2 2 . |NH 2 A method very similar to this, which can be employed at much lower temperatures, is the elimination of hydrogen chloride from 5-chloroamylamine, CH 2 C1'(CH 2 ) 3 'CH 2 NH 2 . This elimination occurs when an aqueous solution of the base is heated on the water-bath; ring formation takes place, and piperidine hydrochloride is formed (Gabriel). These two methods are of great importance in deciding the constitution of piperidine, and therefore indirectly that of pyridine. 2. The ammonia derivatives of various unsaturated aldehydes yield pyridine homologues when distilled (p. 130), e.g. /3-methyl- pyridine is obtained from acrolein ammonia, and collidine from croton-aldehyde ammonia (Baeyer, A. 155, 283, 297). 3. When ethyl acetoacetate is warmed with aldehyde-am- monia, the ester of " Dihydro-collidine-dicarboxylic acid", ie. ethyl trimethyl-dihydro-pyridine-dicarboxylate is produced (Hantzsch) (cf. p. 230): CO 2 Et-CH 2 O-CHMe CH 2 .CO 2 Et MeCO " NH 3 "^COMe C0 2 Et - C CHMe C - CO 2 Et ~~ 3H2 + CMe-NH.MeC 636 XXXVII. SIX-MEMBEREt) IIETEfcOCYCLIC RINGS This loses its two "hydro "-hydrogen atoms when acted on by nitrous acid, and yields ethyl collidine-dicarboxylate, C 5 N(CH 3 ) 3 (C0 2 Et) 2 , from which collidine may be obtained by hydrolysis and elimination of carbon dioxide. If, instead of aldehyde-ammonia, the ammonia compounds of other aldehydes are uitf& homologous bases of the type C 5 H 2 N(CH 3 ) 2 (C n H 2ntl ) are~rmed. In the above reaction a molecule of the acetoacetic ester may be replaced by one of an aldehyde, when the mono-carboxylic esters of dialkylated pyridines are formed, thus : C 6 H 10 O 3 + 2CH 3 .CHO + NH 3 = C 6 H 2 NH 2 (CH 3 ) 2 .C0 2 Et -f 3H 2 O. This is a very important synthetical method (Hantzsch, A. 215, 1, &c.). Two methods of obtaining pyridine derivatives, which indi- cate the relationship of pyridine to quinoline and pyrrole, are : (a) The conversion of quinoline into quinolinic acid or pyri- dine a/3-dicarboxylic acid (p. 544). (b) The conversion of potassium-pyrrole into chloro-pyridine when heated with chloroform, or into pyridine when heated with methylene-chloride: CH:CH\ CHiCH-N CH:CH.N CH:CH/ CH-.CH-CCl r CH:CH.CH Not merely is the ring constitutional formula (p. 534) in perfect harmony with the characteristic properties of pyridine and its derivatives, and also with certain of the synthetical methods of formation, but this formula receives additional support from a study of the number of isomeric forms in which pyridine derivatives occur. Three isomeric mono- substituted derivatives of pyridine are known in each case. They are designated as a-, /?-, and y-derivatives of pyridine, as is shown in the following graphic formula : or as 2-, 3-, or 4-derivatives according to the numbering p. 534. on PYRIDINE 537 In order to determine the position of any given group, it is sought to exchange it for carboxyl; should picolinic acid result, the group occupies the a-position, and should nicotinic or iso- nicotinic, then it fills the fi- or y-position respectively, since in these acids the a-, /?-, and y-positions of the carboxyl have been determined by special means. (See M. 1, 800; 4, 436, 453, 595; B. 17, 1518; 18, 2967; 19, 2432.) Di-derivatives of pyridine containing the same substituent twice can exist theoretically in six isomeric forms. As a matter of fact the six dicarboxylic acids are known (aa -, a/3-, ay-, ap- t /?y-, and ftp- (see p. 538). The isomerism of picoline, C 6 H^N, with aniline, C 6 H 5 NH 2 , which repeats itself in their homologues, is also worthy of notice. Pyridine, C 5 H 5 N (Anderson, 1851), may be prepared from bone-oil, and can be obtained pure by heating its carboxylic acid with lime; the ferrocyanide is especially applicable for its purification, on account of its sparing solubility in cold water. It is also found in the ammonia of commerce. Pyridine is a liquid of very characteristic odour, miscible with water, and boiling at 115. It is used as a remedy for asthma, and also in Germany for mixing with spirit of wine in order to render the latter duty-free. When sodium is added to its hot alcoholic solution, or when solutions of its salts are electrolysed, hydrogen is taken up and piperidine, CglLjN, formed (Ladenburg and Both, B. 17, 513). When heated strongly with hydriodic acid, pyridine is converted into normal pentane. The ammonium iodides, e.g. C 5 H 5 N, CH 3 I, give a character- istic pungent odour when heated with potash, a fact which may be made use of as a test for pyridine bases; it depends upon the formation of alkylated dihydro-pyridines, e.g. di- hydro-methyl-pyridine, C 5 H 6 .N(CH 3 ) (Hofmann, B. 14, 1497). Pyridine is polymerized by the action of metallic sodium to dipyridine, C 10 H 10 N 2 (an oil, b.-pt. 286-290), with the simultaneous production of ^-dipyridyl, C 5 H 4 N C 5 H 4 N (long needles, m.-pt. 114), a compound corresponding to diphenyl (p. 471); both of these yield iso-nicotinic acid when oxidized. An isomeric m-dipyridyl has also been prepared, which gives nicotinic acid when oxidized. Pyridine can be brominated but not nitrated; it can also be sulphonated with the formation of /2-pyridine-sulphonic acid, C & H 4 N (S0 3 H), which with potassium cyanide yields /?-cyano- 638 XXXVII. SIX-MEMBERED HETEROCYCLIC RINGS pyridine, C 5 H 4 N-CN, or by fusion with potash, fthydroxy- pyridine. The three hydroxy-pyridines, C 5 H 4 N(OH) (a-, ft, y-), are best prepared by the elimination of carbon dioxide from the respective hydroxy-pyridine-carboxylic acids. The melting- points are respectively: a, 107; ft 124; y, 148. They pos- sess the character of phenols, and are coloured red or yellow by ferric chloride. As in the case of phloroglucinol, so here also there is a tertiary as well as a secondary form to be taken into account, the former reminding one of the lactams and the latter of the lactims; for instance, y-hydroxy-pyridine may either have the "phenol" formula C 2 H 2 <C 2 H 2 or the p*o "pyridone" formula C 2 H 2 <^jj^>C 2 H 2 , the latter of the two representing a keto-dihydro-pyridine. The two methyl ethers, methoxy- pyridine and methyl -pyridone, which result from these two forms by the exchange of H (of the OH or NH respectively) for CH 3 , are both known, and differ considerably in properties (M. 6, 307, 320; B. 24, 3144). Homologues of Pyridine (cf. Ladenburg, A. 247, 1). Methyl-pyridines or picolines, C 5 H 4 N(CH 3 ). All the three picolines are contained in bone-oil, and probably also in coal- tar. The ftcompound is obtained from acrolein-ammonia (p. 130), and also when strychnine is heated with lime, or when trimethylene-diamine hydrochloride is distilled. They are liquids of unpleasant, piercing odour resembling that of pyridine, and they yield a-, ft, or y-pyridine-carboxylic acid when oxidized. The boiling-points are: a, 129; ft 142, y, 142-144. Ethyl-pyridines, C 5 H 4 N(C 2 H 5 ), are also known. Propyl- and isopropyl pyridines, C 5 H 4 N(C 3 H 7 ), have been carefully investigated on account of their relation to coniine. They are prepared by heating pyridine with the alkyl iodides. Conyrine, C 8 H n N (liquid, b.-pt. 166-168), which is formed when coniine, CgH^N, is heated with zinc dust, and which yields coniine again when treated with hydriodic acid, is a-normal-propyl-pyridine. a-Allyl-pyridine, C 5 H 4 N(C 3 H 5 ), is produced when a-picolino is heated with aldehyde : C 6 H 4 N.CH 3 4-OHC-CH 3 = C 6 H 4 N.CH:CH.CH 3 + H 2 O. Reduction transforms it into inactive coniine (b.-pt. 189-190 ). PYRIDINE CARBOXYLIC ACIDS 539 Bimethyl-pyridines or Lutidines, C 5 H 3 N(CH 3 ) 2 . The pre- sence of three lutidines has been proved in bone-oil and coal- tar (B. 21, 1006; 29, 2996). ay-Lutidine boils at 157, the aa'-compound at 142, and the /ty-compound at 164. The trimethyl-pyridines or collidines, C 5 H 2 N(CH 3 ) 3 , are isomeric with the propyl-pyridines. Some of them are pre- sent in bone-oil, and can be prepared from cinchonine by dis- tilling the latter with caustic potash (p. 560). The aa'y-colli- dirie, which is obtained from the condensation product of ethyl acetoacetate and aldehyde ammonia (p. 230), boils at 171-172. Pyridine-carboxylic Acids (Weber, A. 1887, 241, 1). The pyridine-mono-carboxylic acids, C 5 H 4 N(C0 2 H), are formed by the oxidation of all mono-alkyl derivatives of pyridine, i.e. from methyl-, propyl-, phenyl-, &c., pyridines; also from the pyridine-dicarboxylic acids by the decomposition of one of the carboxyl groups, just as benzoic may be got from phthalic acid. The carboxyl which is in closest proximity to the nitro- gen is the first to be eliminated. Nicotinic acid is also pro- duced by the oxidation of nicotine. The acids unite in them- selves the characters of the basic pyridine and of an acid, and are therefore comparable with glycocoll. They yield salts with HC1, &c., and double salts with HgCl 2 , PtCl 4 , &c.; on the other hand, they form metallic salts as acids, those with copper being frequently made use of for the separation of the acids. (For constitution, see Skraup and Colenzl, M. 1883, 4, 436.) The a-acid is picolinic acid, and forms needles melting at 135. The /?-acid is nicotinic acid, and melts at 231. The y-acid is iso-nicotinic acid, and melts at 309 in a sealed tube. It is noteworthy that all three acids (and also the /3y-dicar- boxylic acid) readily yield up their nitrogen as ammonia when acted upon by sodium amalgam, being thereby transformed into unsaturated acids of the fatty series (Weidel, M. 1890, 11, 501). The constitution of nicotinic acid follows from its relation- ship to quinoline. Quinoline on oxidation yields pyridine a/2-dicarboxylic acid, the constitution of which follows from the constitution of quinoline. When heated, the dibasic acid loses carbon dioxide, yielding a monobasic acid which is not identical with picolinic acid (which can be shown to be the a-acid), and therefore it must be pyridine /2-carboxylic acid. 540 XXXVII. SIX-MEMBERED HETEROCYCLIC RINGS Pyridine-dicarboxylic acids, C 5 H 3 N(C02H)2 a-j8- = Quinolinic acid M.-pt. 190. 0-7- = Lutidinic acid M.-pt. 235. a-a'- = Dipicolinic acid M.-pt. 226. a-j3'- = Iso-cinchomeronic acid M.-pt. 236. /S-j8'- = Dinicotinic acid. . . . .* M. -pt. 323. (3-y- = Cinchomeronic acid M.-pt. 266. Quinolinic acid, which crystallizes in short glistening prisms, is the analogue of phthalic acid, and is obtained by the oxi- dation of quinoline, just as phthalic acid from naphthalene; cinchomeronic and iso-cinchomeronic acids are obtained by the oxidation of cinchonine and quinine. Hydro-pyridines. According to theory, hexa-, tetra-, and dihydro-pyridines may exist. The first of these receive the generic name of " piperidines ", e.g. pipecoline, C 5 H 10 N(CH 3 ), lupetidine, C 5 H 9 N(CH 3 ) 2 , and copellidine, C 5 H 8 N(CH 3 ) 3 ; while the tetrahydro-compounds are termed " piperideins ". Piperidine, CgH^N (Werftitim, Eochleder, 1850), is a colour- less liquid of peculiar odour, slightly resembling that of pepper, and of strongly basic properties yielding crystalline salts. It dissolves readily in water and alcohol, and boils at 106. It occurs in pepper in combination with piperic acid, C 12 H 10 4 (p. 464), in the form of the alkaloid piperine, C 18 H] 8 N0 8 = C H 10 N C 12 H 9 3 , i.e. piperyl-piperidine, which crystallizes in prisms, melting at 129 e ; from this latter it may be prepared by boiling with alkali. (For its formation from pyridine and from pentamethylene- diamine, see pp. 196, 535, 537.) Piperidine is a secondary amine; its imino-hydrogen is replaceable by alkyl and acyl radicals. When its vapour, mixed with that of alcohol, is led over zinc dust, homologous (ethylated) piperidines are formed. When methylated, piperidine yields, as a secondary base, in the first instance, tertiary n-methyl-piperidine, CgHj N(CH 3 ), and then with a further quantity of methyl iodide an ammo- nium iodide, dimethylpiperidonium iodide. The correspond- ing hydroxide does not decompose in the usual manner when distilled, but yields water and an aliphatic base, "dimethyl- piperidine", 7 H 16 N or CH 2 :CH.CH 2 -CH 2 .CH 2 .NMe 2 . The latter forms* a quaternary iodide, the hydroxide of which, when distilled, gives trimethylamine and piperylene, CHMe:CH-CN:CH 2 (exhaustive methylation. For further examples, see Chap, on Alkaloids). QUINOLINE AND ACRIDINE GROUPS 541 XXXVIII. QUINOLINE AND ACKIDINE GROUPS A. Quinoline Group The quinoline group comprises the compounds formed by the condensation of a benzene nucleus with a heterocyclic six- membered ring. The best-known examples are: O Chromone (benzene + pyrone rings), Quinoline (benzene + pyridine), Iso-quinoline (benzene + pyridine), 1. CHROMONE GROUP Chromone, Chromone itself melts at 59 (Buhemann and Stapletwi, J. C. S. 1900, 1185), and the phenyl derivative, /O C-C 6 H 5 flavone, C 6 HX , is the parent substance of a \OO GH number of yellow dyes which occur in the vegetable kingdom. Most of these dyes are hydroxylic derivatives of flavone, and occur in nature in the form of glucosides. As examples we have Chrysin (dihydroxy-flavone), Luteolin (5:7:3':4'-tetrahydroxy-flavone, Kostanedi, Abstr. 1901, 1, 92, 335), Quercitin (3:5:7:3':4'-pentahydroxy-flavone, Herzig, M. 1885, 6, 872), Rhamnetin (3:5:3':4'-tetrahydroxy-7-methoxy- flavone), and Rhamnazm (3:5:4'-trihydroxy-7:3'-dimethoxy- flavone, Perkin and Allison, J. C. S. 1902, 469). 642 XXXVIII. QUINOLINE AND ACRIDINE GROUPS The constitution of these compounds is often arrived at by an examination of the products formed by the action of alcoholic potash on the compound, or, more readily, by aspi- rating air through the dilute alkaline solution; under these conditions rhamnetin yields protocatechuic acid, 3:4-dihydroxy- benzoic acid (p. 459), and phloroglucinol monomethyl ether. 2. QUINOLINE AND ITS DERIVATIVES Quinoline, bears the same relationship to naphthalene that pyridine does to benzene, its molecule consisting of condensed benzene and pyridine nuclei. It occurs, together with derivatives, in both coal-tar and bone-oil, and may be obtained by heating certain alkaloids with potash, e.g. cinchonine yields quinoline itself (Gerhardtj 1842), and quinine gives methoxy-quinoline. Among the various syntheses of quinoline and its deriva- tives the following may be noted: 1. The first synthesis, which was accomplished by Koenigs, was by the oxidation of allyl-aniline by passing its vapour over heated lead oxide: C 6 H 6 .NH.CH 2 .CH:CH a + 20 = C^ + 2H/X 2. One of the usual methods employed for the preparation of pure quinoline is by Skraup's synthesis (B. 14, 1002). In this process aniline is heated with glycerol and sulphuric acid in presence of nitro-benzene or arsenic acid : OH.CH 2 .CH -OH + CH 8 .OH The nitro-benzene simply acts as an oxidizing agent. The formation of acrolein as an intermediate product is to be assumed here, the latter combining in the first instance with aniline to acrolein-anilme, C 6 H 5 N : CH CH : CH 2 . The homo- logues and analogues of aniline yield homologues and ana- logues of quinoline by corresponding reactions; when naph- thylamine is used, the more complicated naphtho-quinolines are formed. SYNTHESES OF QUINOLINE DERIVATIVES 543 3. Baeyer and Drewson (B. 16, 2207) obtained quinoline by the elimination of the elements of water from 0-amino-cinnamic aldehyde : ::CH-CHO _ /CH:CH If 0-amino-cinnamic acid is used, carbostyril (a-hydroxy- quinoline, p. 546) is obtained (Baeyer): TFT + H 2 0. 4. When aniline is heated with aldehyde (paraldehyde) and hydrochloric acid, a-methyl-quinoline (quinaldine) is obtained (Doebner and v. Miller). In this reaction ethylidene-aniline is formed as an inter- mediate product (B. 24, 1720; 25, 2072): OCH.CH 3 Aniline Quinaldine. Here, again, various other primary arylamines may be used instead of aniline, and other aldehydes (B. 18, 3361) or ketones (e.g. B. 19, 1394) instead of paraldehyde. 5. Aniline and acetoacetic acid combine together at tem- peratures above 110 to aceto-acetanilide, CH 3 -CO .CHACO- NS 'CgR^ from which y-methyl-a-hydroxy-quinoline ("methyl- carbostyril ") is formed by the elimination of water (Knorr, A. 1886,236,75): CH 3 CO OH 2 yv/^OJEijj) : OH C 6 H 6 .NH-CO 6 4 \N = C-0 Aniline can also react with acetoacetic ester below 100, yielding ethyl /2-phenyl-amino-crotonate, C 6 H 5 .NH.C(CH 3 ): CH COgCgH*, which yields y-hydroxy-quinaldine when heated (Conrad and Limpach, B. 20, 944): C 2 H 6 O.CO.CH /C(OH):CH C 6 H 5 .NH.C.CH 3 4 \N=C.CH 3 T /3-Diketones and other compounds closely related to aceto- acetic ester also condense with aniline. In place of /5-di- ketones, mixtures of ketones and aldehydes, or mixtures of aldehydes which would yield /3-diketones or /3-ketonic alde- hydes if condensed together (C. Beyer, B. 20, 1767), can be 544 XXXVIII. QUINOLINE AND ACRIDINE GROUPS employed. With acetyl-acetone we obtain ay-dimethyl-quino- line (B. 1899, 32, 3228): These reactions are nearly allied to those already spoken of under 4. 6. 0-Amino-benzaldehyde condenses with aldehydes and ketones under the influence of dilute caustic soda solution, yielding quinoline derivatives (Friedldnder, B. 15, 2574; 16, 1833; 25, 1752). With aldehyde quinoline itself results, and with acetone quinaldine : /CHO CH 2 .E C H <NH 2 +CO.B< ! Acetophenone, acetoacetic ester, malonic ester, diketones, &c., also react in a similar way. Constitution. The above modes of formation (especially 3 and 6) show that quinoline is an ortho-di-substituted-derivative of benzene, and that it contains its nitrogen linked directly to the benzene nucleus; they also show that the three carbon atoms, which enter the complex, form a new hexagon (pyri- dine) ring with this nitrogen and with two carbon atoms of the benzene ring. The latter point also follows from the oxidation of quinoline to pyridine-dicarboxylic acid (Hoogewerff and van Dorp] : Quinoline Quiuolinic acid. We have thus the following constitutional formula: N o N according to which quinoline is constituted in a manner per- fectly analogous to naphthalene, and may be regarded as derived from the latter by the exchange of CH for N, or as formed by the "condensation" of a pyridine and a benzene nucleus. QUINOLINE DERIVATIVES 545 When quinoline derivatives are oxidized, the benzene ring is usually more readily ruptured than the pyridine one, e.g. quinoline yields pyridine-dicarboxylic acid (p. 540). a-Methyl- quinoline gives, on the other hand, 0-acetyl-amino-benzoic acid when oxidized: (For laws governing the oxidation of quinoline derivatives, see W. v. Miller, B. 23, 2252; 24, 1900; M. 1891, 12, 304.) The pyridine nucleus of quinoline takes up hydrogen more readily than the benzene one; thus quinoline is easily con- verted, even by tin and hydrochloric acid, into tetrahydro- quinoline. It can be further reduced to the deca-hydride, but only with difficulty. The three hydrogen atoms of the pyridine nucleus, counting from the N, are designated as a-, ft-, and 7-, and the four hy- drogen atoms of the benzene nucleus as 0-, m-, p-, and a- (ana-) hydrogen atoms, or more commonly the numbering shown above is adopted, the nitrogen atom being numbered 1 and the carbon atoms consecutively 2, 3, &c., up to 8. As no two hydrogen atoms are symmetrically situated in the molecule, seven mono-substituted derivatives of quinoline are in each case theoretically possible. As a matter of fact, all seven quinoline-monocarboxylic acids have been prepared. The position of the substituents follows : (a) from the nature of the oxidation products, e.g. B-quinoline-carboxylic acid (i.e. an acid in which the carboxyl is attached to the benzene nucleus) yields a pyridine-dicarboxylic acid, while a Py-quino- line-carboxylic acid (in which the carboxyl is linked to the pyridine nucleus) yields a pyridine-tricarboxylic acid; (b) from the synthesis of the compound in question. The methyl- quinoline, for instance, which is obtained from o-toluidine by the Skraup synthesis must be the 8-methyl-quinoline : /y\ + C 3 H 6 (OH) 3 + = +4H 2 0, NH 2 \/\/ CH 3 CH 3 N whilst m-toluidine must yield a 7- or 5-, and ^-toluidine a 6-methyl-quinoline. Quinoline (Eunge, 1834) is a colourless strongly refracting liquid of a peculiar and very characteristic odour. It boils at (9480) 2M 546 XXXVIII. QUINOLINE AND ACRIDINE GROUPS 239, is a mono-acid base, forms a sparingly soluble dichromate, (C 9 H 7 N) 2 , H 2 O 2 7 , and is used as an antifebrile. As a tertiary base it yields quinolonium salts (Boser, A. 1893, 272, 221). Nascent hydrogen transforms it first into dihydro-quinoline, C Q H Q N, which melts at 161, and then into tetrahydro-quinoline, /CH CH C 9 H U N, = C 6 H/ *' - * a liquid boiling at 245. Since N JN 1 \ja-2 both of these yield nitrosamines and can be alkylated, they are secondary bases. The tetrahydro-compound exerts a stronger antifebrile action than the mother substance, especially in the form of its ethyl derivative, cairolin (B. 16, 739). Quinoline decahydride, CLK^N, is obtained when strong reducing agents are employed. It forms crystals of a narcotic, coniine-like odour, melts at 48, and boils at 204. Halogen derivatives of quinoline and nitro-quinolines have been prepared by the Skraup reaction, &c.; and, from the reduction of the latter, amino-quinolines, C 9 H 6 N(NH 2 ). The quinoline-sulphonic acids yield cyano-quinolines with potassium cyanide, and hydroxy-quinolines when fused with potash. l-Hydroxy-quinoline, carbostyril, is a quinoline hydroxylated in the pyridine nucleus (see p. 543, mode of formation 3). It crystallizes in colourless needles, melts at 198, and is soluble in alkali, from which it is again thrown down by carbonic acid. Its constitution follows from its formation from o-amino- cinnamic acid (p. 456). Quinaldine, 2-methyl-quinoline, C 10 H 9 N, is contained in coal- tar. It is a colourless liquid of quinoline odour, and boils at 246. When oxidized with chromic acid it yields a quinoline derivative, with permanganate a pyridine-tricarboxylic acid. The hydrogen of the methyl group readily enters into re- action; quinaldine reacts with phthalic anhydride to produce a beautiful yellow dye, quinoline-yellow, C 1 QH 7 N(CO) 2 C 6 H 4 (B. 16, 2602). A mixture of quinoline and quinaldine is transformed into the (unstable) blue dyes, the cyanines, when alkylated and treated with caustic potash. These are used as sensitizers for photographic plates. ftuinoline-carboxylic Acids. All the seven quinoline mono- carboxylic acids, which are possible according to theory, are known. Quinoline-benz-carboxylic acids are those which con- tain the carboxyl group in the benzene nucleus. Cinchoninic acid, guinolineA-carloxylic acid, C 9 H 6 N(CO 2 H), which is obtained by the oxidation of cinchonine with per- ISO-QUINOLINE 547 manganate of potash, crystallizes in needles or prisms and melts at 254. From it is derived quinic acid, -methoxy- quinoline-i-carloxylic acid, C 9 H 5 N(OCH 8 ) C0 2 H, which is ob- tained by oxidizing quinine with chromic acid; it forms yellow prisms, melting at 280. Quinoline-2 : 3-dicarboxylic acid, or acridinic acid, is formed by the oxidation of acridine. 3. ISO-QUINOLINE Iso-quinoline, an isomer of quinoline, occurs along with the latter in coal-tar (B. 18, Ref. 384). It is a solid, melts at 23, and boils at 240. Since oxidation converts it into cincho- meronic acid on the one hand and phthalic acid on the other, it possesses the constitution : Its constitution also follows from its synthesis* from homo- PTT /~i/~\ TT phthalic acid, C 6 H 4 <^ 2 A 2 , in which the substituents are in the o-position. This may be converted into its imide. PTT p/-w C 6 H 4 <^ 2 , by heating the ammonium salt. This imide M30 NH with phosphorus oxychloride reacts as the tautomeride, /CH=C(OH) CgB^f , and yields the corresponding dichloro- iso-quinoline, which is reduced by hydriodic acid and red phosphorus to iso-quinoline. B. The Acridine Group Acridine, C 13 H 9 N (Graebe and Caro), is a basic constituent of the crude anthracene of coal-tar, and also of crude diphenyl- amine. It crystallizes in colourless needles, may be sublimed, and is characterized by an intensely irritating action upon the epidermis and the mucous membrane, and also by the greenish- blue fluorescence shown by dilute solutions of its salts. Acridine stands in the same relationship to anthracene that pyridine does to benzene or quinoline to naphthalene. It may *For synthesis from /3-naphthaquinone see B. 25, 1138, 1493; 27, 198; and for synthesis from benzylaminoacetaldehyde hydro-chloride and sul- phuric acid see E. Fischer, B. 26, 764. 548 XXXVIII. QTJINOLINE AND ACRIDINE GROUPS be regarded as anthracene in which one of the CH-groups of the middle ring is replaced by N. This constitutional formula : is based (a) upon the oxidation of acridine to qumoline- 2 : 3-dicarboxylic acid, and to pyridine tetracarboxylic acid the ^-union between C and N becomes ruptured during the oxidation; (b) upon its synthesis from diphenylamine and formic acid, or formyl-diphenylamine, (C 6 H 5 ) 2 N CHO, with zinc chloride (Bernthsen, A. 224, 1): O -T I'll a Formyl-diphenylamine Acridine. It is also obtained when the vapour of 0-tolyl-aniline is passed through a red-hot tube. Acridine is a tertiary base, and as such combines with alkyl iodides, yielding acridonium iodides. It is a much feebler base than quinoline, and on reduction readily forms a dihydro- derivative, which is not basic. Methyl- and butyl-acridines, phenyl-acridine, C 6 H 4 and naphtho-acridines (i.e. acridines which contain C 10 H 6 instead of C 6 H 4 ) have all been prepared synthetically in an analogous manner. Diamino - dimethyl - acridine, acridme yellow, C 13 H 5 (CH 3 ) 2 (NH 2 ) 2 N, a yellow basic dye, is formed by condensing formic aldehyde with m-toluylene-diarnine, splitting off ammonia, and oxidizing the leuco-base produced. The chrysaniline orphosphin of commerce, a beautiful yellow dye, is diamino-phenyl-acridine, C ]9 H n N(NH 2 ) 2 , since it yields phenyl-acridine when its diazo - compound is boiled with alcohol. Acridine is therefore, like anthracene, a chromogene. The oxygen analogue of dihydro-acridine, C 6 H 6 < is diphenylene-methane oxide, C 6 H 4 <_o>C 6 H 4 , which can XXXIX. AZINE, ETC. GROUP 640 be prepared synthetically and also by distilling euxanthone over zinc dust. It crystallizes in plates, and melts at 9 8 '5. It is on the one hand the mother substance of xanthone, 4 , and its derivative euxanthone or dihydroxy- xanthone, OH C 6 H 3 <^>C 6 H 3 OH, and on the other hand, of the rhodamines and fluoresceins (p. 493). Its tetramethyl- diamino- derivative results from the condensation of formic aldehyde with dimethyl - m - amino - phenol to tetramethyl- diamino-dihydroxy-diphenyl-methane and subsequent elimi- nation of water (ring formation), and is the leuco-compound of formo-rhodamine or pyronine, C 17 H 19 N 2 OC1, into which ifc passes upon oxidation and production of quinoid linking, thus; / C 6 H,.N(CH 3 ) 2 /} H 2 C/ >0 HC/ >0 X C 6 H 3 .N(CH 3 ) 2 XH 3 :N( Leuco-compound Formo-rhodamine hydrochloride. XXXIX. SIX-MEMBERED HETEROCYCLIC COM- POUNDS WITH NOT MORE THAN FOUR CARBON ATOMS IN RING. AZINES, ETC, A number of six-membered heterocyclic compounds, con- taining four carbon and two other atoms, are known, e.g. par- oxazine, with 4C, 10, and IN, the and N in the ^-position. A derivative of this is morpholine, 0<g 2 *g 2 >NH. Simi- larly, thiazines (4C, IS, IN) and diazines (4C, 2N) are known; and these are the parent substances of numerous important dyes. The majority of these dyes are not simple derivatives of oxazines, thiazines, or diazines, but are derived from condensed benzene and oxazine, or benzene and diazene nuclei, and may be compared with anthracene. For example, phenazine is anthracene in which two CH-groups have been replaced by two N-radicals: CH N Anthracene Pheuazine 650 XXXIX. SIX-MEMBERED AZINE GROUP dihydro-phenazine corresponds with dihydro-anthracene, and phenoxazine with dihydro-anthracerie in which one CH 2 has been replaced by and another by NH, e.g. : (I) C 6 H<^>C 6 H 4 (H) CeH^J^CeH, (III) CeH^g^CeH, Dihydro-phenazine Phenoxazine Phentluazine (thio-diphenyl amine). Further, the benzene nuclei may be replaced by those of naphthalene, with the formation of: (IV) C 10 H 6 <C 10 H fl (Y) C 10 H 6 < ( >C 6 H 4 Naphthazine Naphtho-phenoxazine. The compounds (I-III) of the type of dihydro-anthracene are the leuco-compounds of dyes when they contain an amino- (alkyl-amino-) or hydroxy-group in the ^ara-position to the nitrogen. The dyes themselves are obtained from these by oxidation (i.e. elimination of hydrogen), so that they are derived from amino- or hydroxy-phenazines. In this way the eurhodines (mon-amino-compounds) and the toluylene red dyes (diamino-compounds) are derived from phenazine and hydro- phenazine, and similarly the safranines and indulines; Nile blue is derived from naphtho-phenoxazine; and the thionine dyes from phenthiazine. THE DIAZINES The three simple diazines are : :CH Pyridazine. Pyrimidine. Pyrazine. Pyridazine is a colourless liquid, b.-pt. 208, is miscible with water, has an odour of pyridine, and forms soluble salts. (Preparation, cf. B. 28, 451.) Pyrimidine can be obtained from barbituric acid and from methyluracil (p. 287); it forms colourless crystals, m.-pt. 22 and b.-pt. 124. The pyrimidme ring is met with in uric acid and in most purine derivatives (cf. B. 34, 3248). Pyrazine forms colourless prisms, m.-pt. 47, b.-pt. 118, and is basic (J. pr. [ii], 51, 449). Dimethylpyrazine, Ketin, is present in crude amyl alcohol, and can be obtained by the reduction of isonitrosoacetone or by condensation of amino- fHENAZINES 51 acetone. Tetraphenylpyrazine is readily obtained from ben- zoin. Of the compounds formed by the union of a benzene and a diazine nucleus the most important is quinoxaline, C 6 H 4 ^ , which is obtained from 0-phenylene-diamine and \N I C/rl glyoxal. Substituted quinoxalines are formed by condensing tt-dike tones, a-ketonic acids, &c., with 0-phenylene-diamines. Of more importance is the group of compounds containing two benzene nuclei condensed with one diazine ring, e.g. phenazine. Phenazine, or azo-phenylene (p. 549), is obtained by the dis- tillation of barium azo-benzoate, or by leading the vapour of aniline through red-hot tubes; also from nitrobenzene, aniline, and sodium hydroxide at 140, or by the oxidation of its hydro-compound (see below). It crystallizes in beautiful, long, bright-yellow needles melting at 171, and can be readily sublimed. It is only sparingly soluble in alcohol, but readily in ether, and also dissolves in concentrated sulphuric acid to a red solution; the alcoholic solution yields a green precipitate on the addition of stannous chloride. When reduced with am- monium sulphide it yields the colourless hydro-compound, di- hydro-phenazine, C 12 H 10 2 , which may be obtained syntheti- cally by heating catechol with 0-phenylene-diamine: The entrance of hydroxy- or ammo-groups into these azines converts them into dyes. In accordance with modern views of the quinonoicl structure of dyes these derivatives are usually given ortho or para quinonoid formulae : Para, C 6 H 4 <*J=>C 6 H 3 :NH; ortho, C 6 H 4 <g>C 6 H 3 .NH 2 , and similarly for hydroxy derivatives. The amino-compounds are usually termed Eurhodines, and may be obtained by condensing arylamines with o-amino-azo- compounds. Eurhodine, amino-naphtho-tolazine, or CH 3 .C H 3 <N 2 H>C 10 H 6 :NH, obtained from a-naphthylamine and 0-amino-azo-toluene, forms lustrous golden crystals and yields scarlet salts (B. 19, 441 552 XXXIX. SIX-MEMBERED PHENAZINE GROUP 21, 2418; 24, 1337). When heated with concentrated hydro- chloric acid it is converted into the basic and at the same time phenolic compound eurhodol, HO.C 10 H 6 <N 2 >C H 3 .CH 3 or CH 3 .C 6 H 3 <N 2 H>C 10 H 6 :0 (cf. B. 24, 1337). 0-Diamino-phenazine, C 12 HgN 3 (NH 2 ) 2 , is obtained by the oxidation of 0-phenylene-diamine with ferric chloride (B. 22, 355), and is the parent substance of the important dyes of the toluylene red group. When a mixture of ^-phenylene-diamine and m-toluylene-diamine is oxidized in the cold, the beautiful blue compound, toluylene blue, an indamine (p. 434), is formed, which is further oxidized to toluylene red, diamino-tolu-phen- azine, when boiled : NH 2 .C 6 H 4 .NH 2 + NH 2 .C 6 H 3 Me.NH 2 + 20 = NH 2 C 6 H 4 N : C 6 H 2 Me(NH 2 ) : NH + 2 H 2 O NH 2 .C 6 H 4 .N:C 6 H 2 Me(NH 2 ):NH + O = NH 2 C 6 H 3 <>C 6 H 2 Me NH 2 + H 2 0. This diamino-tolu-phenazine is the simplest of the toluylene reds, and its constitution follows from the fact that when diazotized it yields methyl-phenazine. Analogous dyes are neutral red, the hydrochloride of dimethyl-diamino-tolu-phen- azine, NMe 2 .C 6 H 3 <N 2 ^C 6 H 2 MeNH 2 , HC1, and neutral violet, dimethyl -diamino-pheriazine hydrochloride. The leuco- com- pounds are the corresponding derivatives of dihydropheriazine. The group of dyes known as the safranines are related to toluylene red. They are amongst the oldest of the aniline dyes, and include mauve, the first dye prepared by W. H. Perkin, Senr., in 1856. The simplest member of this group is pheno-safranine, NH:C 6 H 3 <^^>C 6 H 3 .NH 2 , which is of historical interest only. The dye safranine is the hydro- chloride of dimethyphenosafranine : 2 \/%NPhClX\/ SAFRANINES 553 I. represents the compound with a paraquinonoid, and II. with an orthoquinonoid structure. The commercial product is usually a mixture of this with a homologue containing the 0-tolyl group in place of the Ph. The method of manufacture consists in the oxidation of mole- cular proportions of j?-toluylene-diamine and 0-toluidine to the corresponding indamine, and then the condensation of this with o-toluidine to give the tolu-safranine. It can be used for cotton mordanted with tannin, and gives red colours. The safranines are beautiful crystalline compounds of a metallic green lustre, readily soluble in water, and dye yel- lowish-red, red, and violet. The solution in concentrated sul- phuric acid is green, becoming blue, violet, and finally red on dilution with water. Reduction gives rise to leuco-compounds, which are diamino-compounds of the as yet unknown substance H 4 (B. 19, 2690, 3017, 3121; 29, 361, 1442, 1870, &c.); treatment with nitrous acid and alcohol yields phenyl-phenazonium chloride. The safranines are there- fore diamino-compounds of phenyl-phenazonium chloride: Numerous other safranines are manufactured. Methylene violet is asymmetric dimethyl - safranine chloride; sqfranine, MN, is a dimethyl-tolyl-safranine chloride; and amethyst violet, tetramethyl- safranine chloride. Parkin's mauve has the for- mula: Ph The aposafranines are analogous to the safranines, but con- tain only one amino- or substituted amino-group, and at least one naphthalene residue in place of a benzene ring. They are divided into Eosindulines and Isorosindulines. The former con- tain the amino group attached to the naphthalene ring and give red shades, the latter contain the amino group attached to a benzene ring and give blue or green shades. Safranines can be diazotized and coupled with alkaline solutions of /?-naphthol. Indoin blue is the hydrochloride of safranine-azo-naphthol, C 20 H 1G N 3 N : N C 10 H 6 OH, HC1. 554 XL. ALKALOIDS PHENOXAZINES AND PHENTHIAZINES Phenoxazine (p. 550) is obtained by heating catechol with o-aminophenol, and crystallizes in plates. The leuco-corapound of nile blue is a diethyldiamino-naphthaphenoxazin. The dye itself, NH:C 10 H 5 <Q>C 6 H 4 .NEt 2 , HC1, obtained by heating the nitroso-derivative of diethyl-w-aminophenol with a-naph- thylamine, is a brilliant green-blue basic dye. Methylene blue, NMe 2 <C 6 H 8 <g>C 6 H 3 :NMe 2 Cl, a valuable blue dye for wool, is formed by the action of ferric chloride on amino-dimethylaniline and carbon disulphide. With nitrous acid it yields methylene green. For constitution cf. Kehrmann, B. 39, 914; Hantzsch, ibid. 1365. XL. ALKALOIDS The group of alkaloids at one time comprised the whole of the nitrogenous basic compounds present in plants or derived from the various plant tissues by distillation. Thus methyl- amine, betaine, asparagine, caffeine, and the opium alkaloids were all grouped together, but as their constitutional formulae were established they were grouped with the compounds to which they were closely related, e.g. methylamine with the primary aliphatic amines, betaine with the alkyl derivatives of flycocoll, and caffeine with the uric acid or purine derivatives, 'he name is now largely restricted to the nitrogenous basic plant constituents which can be regarded as derived from pyri- dine, quinoline, or iso-quinoline, and to those of unknown constitution. They form an extremely important group of compounds on account of their physiological properties, and they constitute the active principles of the common vegetable drugs and poisons. With a single exception they occur exclusively in dicotyle- dons, and as a rule do not exist in the free state, but combined with organic acids in the form of salts. Such acids are malic (p. 247), citric (p. 261), and tannic (p. 460); quinic acid usually accompanies the alkaloids of opium. A few of the alkaloids are built up of carbon, hydrogen, and ALKALOIDS 555 nitrogen, e.g. coniine, nicotine. Such compounds as a rule are liquids and are readily volatile; the majority, on the other hand, contain in addition oxygen, and then are usually crystal- line and non-volatile. All are optically active, and as a rule laevo-rotatory. A few like coniine are secondary bases, but the majority are tertiary, and a few quaternary ammonium compounds. The following reagents as a rule precipitate the alkaloids in the form of complex derivatives from solutions of their salts, viz. tannin, phosphomolybdic acid, a potassium iodide solution of iodine, and also potassium mercuric iodide. They are further characterized by their bitter astringent taste and by their poisonous properties. Each individual alkaloid gives characteristic colour reactions. The alkaloids are usually extracted from plant tissues by lixiviating the finely-divided tissue with acidified water. The extract is then rendered alkaline with ammonia and the free alkaloid separated by filtration, or, if it is at all readily soluble, by extraction with chloroform. For relationship between constitution and physiological properties see P. May, " The Chemistry of Synthetic Drugs ", London, 1911. The structural formula for an alkaloid is usually determined by a study of its more important chemical reactions and of its degradation products. Among the reactions generally studied are: 1. Determination of the number of free hydroxyl groups by acetylation (cf. p. 201). Thus morphine can be shown to con- tain two, codeine one, and papaverine none. 2. Determination of methoxy groups by Zeisel's method or Perkin's modification. Papaverine contains four such groups, narcotine three and codeine one. 3. Study of the action of hydrolysing agents. Esters are hydrolysed, but most other types of linking are resistent to such agents. Narcotine (p. 561) yields opianic acid and hydro- cotarnine, and is presumably an ester derived from these two compounds. Similarly, atropine (p. 565) on hydrolysis yields tropic acid and tropine. As the products of hydrolysis are simpler than the original alkaloid, the elucidation of their constitutions is less difficult. 4. Examination of bhe products of oxidation. Thus codeine contains a secondary alcoholic group, as on oxidation it yields a ketone, codeinone, containing the same number of carbon 556 XL. ALKALOIDS atoms. Coniine when oxidized yields pieolinic acid, and must thus be an a- substituted derivative of pyridine. Cinchonine yields quinoline-y-carboxylic. acid. 5. Determination of the primary, secondary, tertiary, or quaternary nature of the base. 6. Study of the degradation products obtained by exhaus- tive methylation. As an example of this method the simple secondary amine piperidine may be taken. When methylated by means of methyl iodide it yields first the tertiary amine methylpiperidine, and finally the quaternary ammonium iodide, dimethylpiperidonium iodide. This with moist silver oxide yields the quaternary base, which on distillation decomposes into water and an unsaturated aliphatic tertiary amine: = H 2 O f CH 2 :CH.CH 2 .CH 2 .CH 2 .NMe 2 . When methylated and treated with silver oxide this un- saturated base yields a quaternary hydroxide, which splits up into water, trimethylamine, and A aS pentadiene when dis- tilled: 7. An examination of the products obtained by fusing the alkaloid with potash or by distilling it with zinc dust. Thus morphine and zinc dust yield phenanthrene together with other products, and hence the molecule of morphine probably contains a phenanthrene ring. Papaverine, when fused with potash, yields dimethoxy-iso-quinoline and 3:4-dimethoxy- toluene, and hence papaverine is probably an iso-quinoline derivative. The processes of fusion with potash and distilla- tion with zinc dust require high temperatures, and as molecular rearrangements occur much more readily at high than at low temperatures, the conclusions drawn from a study of the products formed during such processes shonld be accepted with a certain amount of reserve unless supported by other evidence. The alkaloids can be grouped according to their origin, e.g. the opium alkaloids, bases from solanine, &c., or according to the heterocyclic ring which they contain. The latter method is adopted here, and we thus have the pyridine, quinoline, iso- auinoline, and phenanthrene groups. PYRIDINE ALKALOIDS 557 A. Alkaloids derived from Pyridine Coniine, dextro-rotatory a-normal-pi'opyl-piperidine, C 5 H 10 N (C 3 H 7 ), is the poisonous principle of hemlock (Conium macu- latum). It is a colourless dextro-rotatory liquid of stupefying odour, sparingly soluble in water, and boils at 167. Hy- driodic acid at a high temperature reduces it to normal octane, while nitric acid oxidizes it to butyric acid, and potassium permanganate to picolinic acid (hence the a-position). Ladenburg has prepared it synthetically by reducing a-allyl- pyridine (p. 538) in alcoholic solution by means of sodium (B. 19, 2578): C 5 H 4 N(C 3 H 6 ) + 8H = C 6 H 10 N(C 3 H r ). The pyridine ring is reduced to a piperidine ring, and at the same' time the unsaturated allyl side-chain is reduced to a %-propyl group. The a-carbon atom is an asymmetric carbon atom, i.e. it is attached to four different monovalent radicals, and the whole molecule is asymmetric. The synthetical pro- duct is optically inactive, and thus differs from the natural product, but it has been resolved by fractional crystallization of the d-tartrate into dextro-coniine and a laevo-coniine. The relations of these two bases to one another and to the inactive modification are the same as that of dextro- to laevo-tartaric acid and to racemic acid. Nicotine, C 1 pH 14 N ? , is the poisonous constituent of the tobacco plant, in which it exists in combination with malic and citric acids. It is a colourless, oily liquid soluble in water, and is Isevo-rotatory. It rapidly oxidizes in contact with the air, and boils at 247. It is a di-tertiary base, and therefore readily combines with methyl iodide. On oxidation with permanganate it yields nicotinic acid, and hence must be a ^-pyridine derivative. It has been synthesised recently by Pictet (C. E. 1903, 137, 860), and been shown to be a-pyridyl- N-methyl-pyrrolidine : OH, -OH, The method of synthesis is as follows: Nicotinic acid is transformed first into its ethyl ester, and then into the amide; 558 XL. ALKALOIDS this with bromine and alkali (Hofmann's reaction, pp. 107, 183) gives /?-amino-pyridine, and when the salt of this base with mucic acid (p. 259) is distilled, N-pyridyl-pyrrole, N< /CH:CH is formed. When the vapour of this compound is passed through a heated tube, it is transformed into the isomeric a-pyridyl-pyrrole, CH-CH This forms a potassic derivative which with methyl iodide CH-CH CH N.CH 3 rCH 3 I and this, when distilled with lime, gives a-pyridyl-N-methyl-pyrrol, which can be converted into a-pyridyl-N-methyl-pyrrolidine (z-nicotine) by the addition of hydrogen. The racemic alkaloid thus obtained may be resolved into its optically active components by the aid of d-tartaric acid when J-nicotine-d-tartrate crystallizes out first. B. Bases derived from Quinoline Among tnese are the alkaloids contained in the barks of certain species of Cinchona. (a) Quinine, C 2 qH 24 2 N 2 -f 3H 2 0, a diacid base of intensely bitter taste and alkaline reaction, of which the sulphate and chloride are universally used as febrifuges. It crystallizes in prisms or silky glistening needles, melts at 177 when anhydrous, is sparingly soluble in water, and is laevo-rotatory. QUINOLINE BASES 559 The quinine salts in dilute solution are characterized by a magnificent blue fluorescence. As a base quinine is a tertiary diamine, but it contains in addition as its reactions show one hydroxy-, one methoxy- group and an ethylene linking, and seems to be built up of two different ring systems, in accordance with the following formula : (CH 3 0) - C 9 H 5 N The first of these represents the radical of a 6-methoxy- quinoline, and this compound is obtained when quinine is fused with potash. The second system probably possesses a ring similar to that of tropine, since it yields as decomposition products sometimes a pyridine derivative (e.g. jS-ethyl-pyridine on fusion with alkali), and sometimes benzene derivatives containing no nitrogen (e.g. a phenolic compound, Ci H 12 OH, together with ammonia, on successive treatment with phos- phorus pentachloride, potash, and hydrobromic acid). It yields quinic acid, 6-methoxy-quinoline-4-carboxylic acid, CgH 5 N(OCH 3 )C0 2 H (p. 547), and meroquinine when oxidized with dichromate mixture. Meroquinine appears to be either (a) 3-vinylpiperidyl-acetic acid (B. .30, 1326), or (b) 3-vinyl-4-methylpiperidine-4-car- boxylic acid (B. 28, 1060): (a) ,n-<cr,!r: (6) as it yields loiponic acid, piperidine-3 : 4-dicarboxylic acid, when oxidized with permanganate. The formulae suggested for quinine are therefore either : CH 2 - CH 2 CH 2 --- CH CH : CH 2 CH 2 - CH 2 or N C(OH)(CH2X) . CMe CH 2 - CH . CH where X represents the 6-methoxy-quinoline residue attached to the CH 2 group in position 4. Quinine is a valuable drug in cases of malaria; numerous 560 XL. ALKALOIDS substitutes are now employed, especially derivatives of quinine which are free from bitter taste. Various esters are used, e.g. aristoquinine is diquinine car- bonate, euquinine is ethyl quinine carbonate, and saloquinine is quinine salicylate. (b) Cinchonine, C 19 H 22 ON 2 , is similar to quinine, but with- out the methoxy group in the quinoline nucleus. It crystal- lizes in colourless prisms, sublimes readily, and is not so active a febrifuge as quinine. When oxidized with dichromate and sulphuric acid it yields cinchoninic (quinoline- 4 -carboxylic) acid and meroquinine; with permanganate it yields cincho- tenine and carbonic acid. Cinchotenine no longer combines with hydrogen chloride, and in the oxidation the double link- ing present in cinchonine has been removed and a carboxylic group introduced. When treated with PC1 5 and then with alcoholic potash, cinchonine loses a molecule of water, yielding cinchene, C 19 H 20 N 2 , which can be hydrolysed by 25 per cent phosphoric acid to lepidine (4-methyl-quinoline) and mero- quinine. (c) Conchinine, C 2( )H 24 2 N 2 , and Cinchonidine, C 19 H 22 ON 2 , are probably stereoisomeric with quinine and cinchonine respectively, and are milder in their action. These are but a few of the numerous alkaloids present in these barks. In addition, organic acids (e.g. quinic and quino- tannic) and neutral substances are also present. C. Bases derived from /so-Quinoline (a) Papaverine, C 20 H 21 4 N, is found (1 %) together with narcotine, narceine, laudanosine, laudanine, and the morphine alkaloids in opium, the solid obtained by drying the juices extracted from the seed vessels of Papaver somniferum. In addition to some twenty alkaloids, many of which are present in only small quantities, opium also contains fats, resins, sugars, albumins, &c. The alkaloid crystallizes in prisms, m.-pt. 147, and is optically inactive. It has hypnotic pro- perties, but not to the same extent as morphine. It is a ter- tiary base, and all four oxygen atoms are present as methoxy groups, and when hydrolysed with hydriodic acid the corre- sponding tetrahydroxy-derivative, papaveroline, C 16 H 13 4 N, is formed. When oxidized with permanganate it yields first papareraldine, C 20 H 19 5 N, and finally dimethoxy-isoquinoline- carboxylic acid and a-carbocinchomeronic acid (pyridine-1 : 2 : 3- /SO-QUINOLINE BASES 561 carboxylic acid). When fused with potash it takes up two hydrogen atoms, and yields 4 : 5-dimethoxy-iso-quinoline and 3 : 4-dimethoxy toluene. From these and other reactions G. Goldschmudt concluded that the base is Si^-dimethoxybenzyl-^'ib'-dimethoxy-iso-qidnoline: _OMe /~ \OMe and this formula has been confirmed by Pictet and Gan's syn- thesis (B. 1909, 42, 2943) by the following steps: 1. C 6 H 4 (OMe) 2 C 6 H 3 (OMe) 2 .CO.CH 3 Veratrole or Friedel- Acetoveratrone l:2-dimethoxybenzeue Crafts' C 6 H 3 (OMe) 2 .CO.CH:N.OH Amyl nitrite Isonitrosoacetoveratrone C 6 H 3 (OMe). 2 . CO - CH 2 . NH 2 HC1 SnCl a Amino-acetoveratrone hydrochloride. 2. CHO.C 6 H 3 (OMe)OH CHO.C 6 H 3 (OMe) 2 Vanillin methylated MethylvaniUin C 6 H 3 (OMe) 2 .CH(OH).CN C 6 H 3 (OMe) 2 .CH(OPI).C0 2 H HCN hydrolysis C 6 H 3 (OH) 2 .CH 2 .C0 2 H C 6 H 3 (OMe) 2 .CH 2 .C0 2 H HI Homoprotocatechuic acid methylated Homoveratric acid C 6 H 3 (OMe) 2 .CH 2 .COCl Homoveratroyl chloride. 3. Amino-acetoveratrone hydrochloride and homoveratroyl chloride condense in the presence of cold potassium hydroxide, yielding (OMe) 2 C 6 H 3 CO - CH 2 . NH . CO . CH 2 . C 6 H 3 (OMe) 2 ; this can be reduced to the corresponding secondary alcohol vphich reacts with dehydrating agents, losing two molecules of water and forming 3' :4'-dimethoxybenzyl- 4: 5-dimethoxy-iso- quinoline, which is identical with papaverine. (b) Laudanosine, C 21 H 27 4 N, crystallizes in needles, m.-pt. 89, and is dextro-rotatory. It has been shown by Pictet and Athanescu (B. 33, 2346) to be an N-methyl-tetra-hydropapa- verine, and has been synthesised by Pictet and Finkektein (C. E. 1909, 148, 295). (c) Narcotine, C 22 H 23 7 N, occurs in opium (6 per cent), crystallizes in colourless needles, m.-pt. 176, and is Isevo- rotatory. It is a feeble tertiary base, and its salts are readily hydrolysed by water. It contains three methoxy groups, and (B480) " 2N 562 XL. ALKALOIDS when hydrolysed by dilute acids or alkalis, yields opianic acid and hydro-cotarnine. When reduced it yields meconine and hydro-cotarnine, and when oxidized yields opianic acid and cotarnirie, and when heated with alkalis at 220 yields methyl- amines, thus indicating that the N-atom is methylated. The racemic compound has been synthesised in small quan- tities (PerUn and Robinson, J. C. S. 1911, 776) by boiling an alcoholic solution of cotarnine and meconine, and has been resolved by means of d-bromo-camphor-sul phonic acid. CH 5 Narcotine, OMe OMe Both opianic (2 : 3-dimethoxy-6-aldehydo-benzoic acid) acid and cotarnine have been synthesised. " The former by Fritsch (A. 301, 351) and the latter by Salway (J. C. S. 1910, 1208): The structural formula: was deduced by Eoser for cotarnine by a study of its degrada- tion products. When methylated and decomposed by alkalis it yields an aldehyde, cotarnone, which on further oxidation gives a methoxy-dibasic acid, known as cotarnic acid, and this with hydriodic acid and phosphorus at 160 yields gallic acid (3:4:5-trihydroxybenzoic acid). Although cotarnine itself is not an iso-quinoline derivative, its salts are. The salt forma- tion is accompanied by a closing of the ring (cf. Debbie, Lauder, and Tinkler, J. C. S. 1903, 598): /SO-QUINOLINE BASES 563 Hydro-cotarnine is also a reduced iso-quinoline derivative : The steps in the synthesis of cotarnine are : Myristic aldehyde (3-methoxy-4:5-methylenedioxy-benzaldehyde) 3-methoxy- Perkin's synthesis. 4 : 5-methylenedioxy-cinnamic acid > corresponding dihydro red. acid acid amide /3- 3 -methoxy -4 : 5-methylenedioxy- co. phenylethylamine * phenacetyl-derivative of amine * 8-me- thoxy-6 : 7-methylenedioxy-l-benzyl-3 : 4 -dihydro -iso-quino- line - 1-benzylhydrocotarnine * cotarnine. Methochloride H 2 S0 4 with tin and HC1. +Mn0 2 . e (d) Hydrastine, C 21 H 21 6 N, occurs in the roots of Hydrastis canadensis, and differs from narcotine by having no methoxy group in the iso-quinoline ring. When oxidized it yields opianic acid and hydrastinine, which is the analogue of cotar- nine. (Synthesis, cf. Freund, B. 20, 2403.) (e) Berberine, C 20 H llr 4 N, H 2 0, is the chief alkaloid present in Hydrastis, but has not marked physiological properties. The probable structural formula is I. (Perkin and Robinson, J. C. S. 1910, 305): CH 2 I. CH (/) Corydaline, C 22 H2 7 4 N, from Corydalis cava, crystallizes in prisms, m.-pt. 134'5 , and contains four methoxy groups. The structural formula suggested by DdbUe and Lander ( J. C. S. 1903, 605) is II: CH 2 /Y Xc ii. 1 1 OMeL IL, N CHMe <T \__OMe [ 2 / V)Me. \. / 564 XL. ALKALOIDS D. The Morphine Group of Bases The three alkaloids morphine, codeine, and thebaine are characterized by containing a phenanthrene nucleus in addi- tion to a nitrogen ring. They are all present in opium. (a) Morphine, C 17 H 19 3 N, constitutes on the average 10 per cent of opium. It crystallizes in small prisms (+H 2 0), melt- ing and decomposing at 230, has a bitter taste, and is a valu- able soporific. It is a mono-acid tertiary base, containing two hydroxyl groups, one of which is phenolic and the second alco- holic. When distilled with zinc dust it yields phenanthrene together with pyrrole, pyridine, and trimethylamine. Further proof of the presence of the phenanthrene nucleus has been afforded by the process of exhaustive methylation. With methyl iodide it yields codeine methiodide, formed by the methylation of the phenolic hydroxyl group and addition of methyl iodide to the tertiary N-atom. This product, with potassium hydroxide, loses hydrogen iodide and yields a tertiary base, methylmorphimethine, which with acetic anhydride gives 3-methoxy-4-hydroxy-phenanthrene (methylmorphol) and hydroxyethyldimethylamine, OH.CH 2 -CH 2 .NMe 2 . The for- mula suggested by Pschorr is : CH, NCH 3 (b) Codeine, C 18 H 21 3 N, is a methyl derivative of morphine, and can be obtained from the latter by methylation of its phenolic group. When oxidized it yields the ketone codeinone, and this with acetic anhydride yields hydroxyethyl-methyl- amine and 3-methoxy-4 : 6-dihydroxy-phenanthrene. (c) Thebaine is morphine in which both phenolic and alco- holic hydroxyls are methylated. Numerous alkyl derivatives of morphine are manufactured and used as drugs in place of codeine. Dionine is ethyl- morphine hydrochloride, peronine is benzylmorphine hydro- chloride, heroin is diacetylmorphine. For synthetical products allied to morphine see Knorr, A 301, 1; 307, 171, 187; B. 32, 732. STRYCHNINE, SOLANINE, AND COCA BASES 565 E. Strychnine Bases Strychnos nitx vomica and certain other beans contain : (a) Strychnine, C 21 H 22 2 N 2 . This is excessively poisonous, produces tetanic spasms, crystallizes in four-sided prisms, and yields quinoline and indole when fused with potash, /3-picoline when distilled with lime, and carbazole when heated with zinc dust. It is a mono-acid tertiary base, and melts at 284. (For suggested formula see Perkin and Robin- son, J. C. S. 1910, 305.) (b) Brucine, C 23 H 26 4 N 2 , 4H 2 0, which crystallizes in prisms, and is converted into homologues of pyridine on fusion with potash. F. Solanine and Coca Bases Atropine and hyoscyamine are isomeric bases of the for- mula C 17 H 23 3 N, which can be respectively prepared from Atropa Belladonna (Deadly Nightshade) and Datura Stramonium, and which are remarkable for their mydriatic action (power of dilating the pupil of the eye). Atropine crystallizes in colourless prisms or needles melting at 115, possesses an extremely bitter taste, is optically in- active, and is hydrolysed by baryta water to (//-tropic acid tropine. The alkaloid can be synthesised by evaporating dilute hydrochloric acid solution of tropine and tropic acid. A complete synthesis of atropine has been accomplished, as both tropic acid and tropine have been synthesised. When optically active (d- and I) tropic acids are used, a dextro- and a laevo-rotatory atropine result (B. 22, 2590). And if, instead of tropic acid itself, other organic acids are employed, homologous bases, the "tropeines", are obtained; thus mandelic acid yields homatropine, C 16 H 21 N0 8 , which exerts like atropine a mydriatic action, although a less lasting one (Ladenburg, A. 217, 82; Jowett and Pyman, J. C. S. 1909, 1090). Tropine itself is a cycloheptanol with a nitrogen bridge : CH 2 -CH CH 2 NCH 3 CH-OH CH 2 .CH CH 2 (fTiUsWter, B. 1898, 31, 1538, 2498, 2655). For synthesis cf. Willslatter, A. 1901, 317, 307. 566 XL. ALKALOIDS It is a tertiary base, crystallizes in plates, m.-pt. 62, and b.-pt. 220. On oxidation it yields the ketone tropinone, and then tro- pinic acid, or N-methyl-pyrrolidine-a-carboxylic-a! '-acetic acid. Concentrated hydrochloric acid converts it into tropidine, CHjj-CH CH 2 NCH 3 CH CH 2 -CH CH 2 an oily base distilling at 162, and also obtainable by the elimination of carbon dioxide from anhydro-ecgonine. Ecgonine, or tropine-carboxylic add, CHjs-CH CH-CO 2 H NCH S CH-OH CH 2 .CH OK, crystallizes with one molecule of water, and may be obtained by the hydrolysis of products contained in coca leaves. It melts at 198, and is laevo-rotatory; and on warming with alkalis, gives iso-ecgonine, which is dextro-rotatory. As an alcohol it forms a benzoyl derivative, and as an acid a methyl ester. (See Cocaine.) Cocaine, or benzoyl-l-ecgonine methyl ester, CH 2 -CH CH.C0 2 CH S NCH 3 CH.O-COC 6 H 6 CH 2 -CH CH 2 is the active constituent of the coca leaf (Erythroxylon coca); it melts at 98, is Isevo-rotatory, and is used in surgery for deaden- ing pain. It has been synthesised by the action of benzoic an- hydride and methyl iodide on ecgonine (B. 1885, 18, 2953). Hyoscyamine, which crystallizes in needles or plates, melt- ing at 109, resembles atropine closely, and is readily trans- formed into the latter under the influence of various alkalis (Will, B. 21, 1725, 2777). In contact with water it is slowly hydrolysed to /-tropic acid and inactive tropine. Atropine is racemic hyoscyamine. Various substitutes for cocaine have been recommended, as its solutions do not keep well. Willstatter (B. 29, 1575, 2216) obtained an isomeride of ecgonine by the addition of HCN to tropinone (p. 566) and subsequent hydrolysis, and from this ETHEREAL OILS 567 a -cocaine was obtained by benzoylation and esterification. a-Cocaine contains both C0 2 Me and COPh groups attached to the same carbon atom. a-Eucaine is a cheap substitute for cocaine prepared from triacetonamine, NH<^QJ^ 2 [Qg 2 ^>CO (p. 134), by addition of HCN, hydrolysis, benzoylation of the hydroxy-acid thus formed, and final methylation of the imino and carboxylic groups. Its structure is: /3-Eucaine has the formula: .;;: : NH< (Harries, B. 29, 2730). XLI. TEEPENES AND CAMPHORS For history of terpenes see Tilden, Science Progress, 1911, 6, 46. Cf. Wallaces "Terpene und Camphor", 1909. Ethereal Oils. Many plants, especially varieties of Coniferse and of Citrus, contain, in their blossoms and fruits, oily sub- stances to which they owe their peculiar fragrance or odour, and which can be obtained from them by distillation in steam or by pressure. These oils, "ethereal oils", were formerly grouped together in a special class, but now they are recog- nized as being more or less heterogeneous; thus oil of bitter almonds is benzoic aldehyde, and Roman oil of cumin is a mixture of cymene and cumic aldehyde, &c. Many of these ethereal oils contain unsaturated hydrocarbons, which are usu- ally termed terpenes. The common hydrocarbons met with have the general formula C 10 H 16 , and are spoken of as terpenes proper; but, in addition to these, hydrocarbons, represented by the formula C 5 H 8 and known as hemiterpenes, exist. The commonest of these is isoprene, obtained by distilling caout- chouc. Hydrocarbons represented by the formula C 15 H 24 are termed sesquiterpenes, and the more complex hydrocarbons, (C 5 Ho) n , polyterpenes. Certain ethereal oils consist chiefly of such hydrocarbons, e.g. turpentine, oil of citron, orange oil, and oil of thyme. Other oils contain appreciable amounts of oxy- genated compounds, mainly of an alcoholic or ketonic character, 668 XLI. TERPENES AND CAMPHORS e.g. camphor and menthone, C 10 H 16 0, pulegone, &c. Many of these terpenes and ketones are reduced benzene derivatives, e.g. limonene, menthone; others again are more complex ring compounds, e.g. pinene and camphor. In addition to these two groups of compounds a third group has been discovered within recent years, namely, open-chain olefinic alcohols, alde- hydes, or ketones, e.g. citronellal, geraniol, linalool. The terpenes are widely distributed in the vegetable king- dom, especially in the Coniferse (Pinus, Picea, AUes, &c.), in the varieties of Citrus, &c. The products which are isolated in the first instance from the individual plants, and which according to their source are designated terpene, citrene (from oil of citron), hesperidene (from oil of orange), thymene (from thyme, carvene (from oil of cumin), eucalyptene, olibene, &c., have for the most part the formula C 10 H 16 , and approximately jqual boiling-points (160- 190); they are not, however, chemical individuals, but mixtures of isomeric compounds. With the exception of camphene they are all liquid, but it is hardly possible to separate them completely by fractional distillation (see table, p. 578, for boiling-points). The terpenes can, however, be obtained chemically pure from crystalline derivatives. Quite recently, numerous compounds belonging to this class have been synthesised. For simplicity the terpenes and allied oxygen compounds (camphors) may be divided into the following groups: A. Open-chain olefinic compounds. B. Monocyclic terpenes (mainly reduced benzene deriva- tives). C. Complex cyclic terpenes. Practically all the compounds dealt with in these three divisions could have been discussed under the aliphatic and cyclic compounds. A clearer view, however, of their relation- ships is obtained by bringing them together under the general heading of terpenes and camphors. A. Open-chain Olefinic Terpenes and Camphors Isoprene, the best-known hemiterpene, is a diolefine repre- sented by the constitutional formula, CH 2 : CMe CH : CH 2 , 2-methyl-A 1:3 -butadiene. It is a colourless liquid, b.-pt. 37, is formed by the dry distillation of rubber, or by decompos- ing turpentine at a dull red heat (cf. Staudinger, B. 44, 2212). At 300 it undergoes polymerization to diisoprene (probably CITRONELLAL 569 dipentene), and is transformed into products analogous to rubber when treated with concentrated hydrochloric acid, when kept for some time or when exposed to sunlight in fche presence of traces of acid. Two syntheses of isoprene are of interest. (a) From methyl -pyrrolidine by exhaustive methylation (Euler, J. pr. [ii], 57, 132): CH 2 CH 2 , H _ ^" CHMe CH 2 ^ methylated CHMe CH 2 :CH.CHMe.CH 2 .NMe 2 CH 2 : CH CHMe CH 2 NMe 3 I methylated __ C H 2 :CH.CMe:CH 2 + NMe 3 + HL KOH (b) From dimethyl-allene by the addition of two molecules of hydrogen bromide and subsequent elimination of the same (Ipatieff, ibid. 55, 4): CMe 2 :C:CH 2 CMe 2 Br.CH 2 .CH 2 Br CH 2 :CMe.CH:CH 2 . It has been suggested that indiarubber should be syntb.esised from isoprene, but the cost of the isoprene has so far interfered with the adoption of this method on the commercial scale. Practically all the natural products belonging to this group contain oxygen and are either aldehydes or alcohols. Citronellal, CH 2 : CMe . CH 2 . CH 2 . CH 2 - CHMe - CH 2 CHO, is an example of an olefine aldehyde; it is present in citronella oil and also in lemon-grass oil, together with citral and geraniol. It has b.-pt. 205-208. Its aldehydic nature is proved by the readiness with which it is reduced to a primary alcohol, citron- ellol, and oxidized to a monobasic acid, citronellic acid, con- taining the same number of carbon atoms. By oxidizing its dimethyl-acetal, Harries and SchauwecJcer (B. 34, 1498, 2981) obtained a dihydroxy-derivative, thus proving the presence of an olefine linking; and on farther oxidation with chromic anhydride they obtained the acetal of a keto-aldehyde contain- ing nine carbon atoms, thus proving that the double bond is between the last and last but one carbon atoms with respect to the aldehyde group: CH 2 :CMe(CH 2 ) 3 .CHMe.CH 2 .CHO -f 4O = OO 2 -f- H 2 O + O:CMe(CH 2 ) 3 .CHMe.CH 2 .CHO. The positions of the methyl groups are proved by the rela- 670 XLI. TERPENES AND CAMPHORS tionship of the aldehyde to isopulegol, into which it is trans- formed when kept for some time, or more quickly when heated with acetic anhydride at 180: The constitution of pulegol follows from the fact that when oxidized it yields isopulegone, and this with baryta is trans- formed into pulegone by the wandering of an olefine linking. Pulegone An interesting reaction of citronellal is its oxidation in alkaline solution with permanganate, when it yields acetone and /?-methyladipic acid, a result which would lead to the con- clusion that the double bond is in position 5:6 with respect to the CHO group. The only manner of reconciling this reaction with the reactions already given is the assumption that in the oxida- tion in alkaline solution a wandering of the double bond occurs : CH 2 : CMe (CH 2 ) 3 CHMe CH 2 CHO CMe 2 :CH(CH 2 ) 2 . CHMe -CH 2 . CHO. Citral or geranial, C 10 H 16 0, occurs in both oil of lemons and of oranges, and may also be obtained by the oxidation of geraniol. Lemon-grass oil contains 70-80 per cent. It is a colourless oil, and distils at 110-112 under 12 mm. pressure. Its constitution is represented as: CMe 2 : CH CH 2 CH 2 CMe : CH CHO. Its aldehydic nature follows from its reduction to geraniol, and its oxidation to an acid containing the same number of carbon atoms, namely, geranic acid. Its unsaturated character and the positions of the double bonds within the molecule follow from its general properties, but more especially (a) from its products of oxidation, viz. acetone, laevulic acid, and carbon dioxide : CMe 2 : ! CH.CH 2 .CH 2 -CMe: j CH-CHO MejjCO + CO 2 H-CH 2 .CH a .COMe -f 20O a ; GERANIOL 671 (b) from its conversion into methyl-heptenone and acetalde- hyde by means of potassium carbonate: CMe 2 :CH.GH 2 .CH 2 .CMe:CH.CHO=CMe 2 :CH.CH 2 .CH 2 .COMe + H 2 +CH 3 .CHO. When heated with potassium hydrogen sulphate, citral is con- verted into ^Mjymene. Both citral and geranic acid have been synthesised by Earlier and Bouveault (C.E. 1896, 122, 393). 1-Methyl-A'- heptenone reacts with metallic zinc and iodo -acetic acid (Reformatsky reaction), yielding the compound: H 2 .CO a H L s With dilute acid this yields the hydroxy-acid: CMe 2 : CH CH 2 CH 2 CMe(OH) CHj CO 2 H, and when this is distilled with acetic anhydride, water is eliminated and geranic acid formed. Geranic acid, when reduced in the form of its ethyl ester with sodium and amyl alcohol, yields i-rhodinic acid: CMe 2 : CH CH, CH 2 - CHMe CH 2 C0 2 H, which is structurally isomeric with citronellic acid; and when ethyl rhodinate is reduced with sodium and alcohol, the corre- sponding primary alcohol, rhodinol, is formed. Citral occurs in two stereoisomeric forms, termed a- and 6-citrals. They are both inactive, and the isomerism is of the same type as that met with in the crotonic acids and fumaric and maleic acids (p. 243). Geraniol, C 10 H 18 0, is the alcohol corresponding with citral, and is the chief constituent (90 per cent) of Indian geranium oil, which is largely used for adulterating rose oil. Its con- stitution follows from its relationship to citral and geranic acid, into which it is readily oxidized. By reducing citral with alcohol and sodium amalgam, two stereoisomeric alcohols, geraniol and nerol, are obtained, and both yield citral when reoxidized. Both alcohols yield ter- pineol by the action of acetic acid containing 1 to 2 per cent of sulphuric acid, but nerol reacts about nine times as readily as geraniol. The formation of terpineol can be accounted for by the addition and withdrawal of water. The two alcohols 572 XLI. TERPENES AND CAMPHORS are structurally identical, and are represented by the two stereochemical formulae : H.C.CH 2 .OH 01 I. 1| IL CMe 2 :CH.(CH 2 ) 2 -C.CH 3 CMe 2 :CH.(CH 2 ).C.CH 3 Geraniol Nerol. as No. II would lose water more readily than No. I to form a six-membered ring. It is probable that citral a corresponds with geraniol, and citral I with nerol. Linalool or coriandrol is isomeric with geraniol, into which it is readily transformed by the action of dilute organic acids. It occurs as linalyl acetate in lavender, sage, and coriander oils. It is optically active, reacts as a tertiary alcohol, and hence is structurally- and not stereo-isomeric with geraniol. Its reactions agree best with the formula: CMe 2 : CH CH 2 . CH 2 CMe(OH) CH : CH^ and its conversion into geraniol probably depends upon the addition and subsequent removal of water, the glycol, CMe 2 :CH.CH 2 .CH 2 .CMe(OH).CH 8 .CH 2 .OH, being formed as the intermediate product. /-Linalool reacts with acetic anhydride, yielding nerol, geraniol, and d-terpineol. Compounds of this type with the carbon system : 7654321 are readily transformed into derivatives of j9-cymene by union between carbon atoms numbers 1 and 6 (cf. p. 571), or into tetrahydrobenzene derivatives by union of numbers 2 and 7 (cf. lonone, p. 589; also conversion of citral into a- and /?-cyclo-citrals, cyclic /?y and a/3 unsaturated aldehydes). B. Monoeyelie Terpenes and Camphors I. Terpenes. These compounds are to be regarded as hydro- derivatives of cymene (p. 352). Their close relationship to cymene can be shown in very different ways: e.g. (a) the hydrocarbon terpinene when heated with iodine is transformed into ^-cymene, i.e. ^-methyl-isopropyl benzene; (b) the ketonc MONOCYCLIC TERPENES 573 carvone when heated with mineral acids yields carvacrol, i.e. l-methyl-2-hydroxy-4-isopropyl benzene (p. 417); (c) on oxi- dation many terpenes yield terephthalic acid; (d) when bro- minated and then reduced many monocyclic terpenes yield benzene hydrocarbons (B. 1898, 31, 2068). The unsaturated nature of these compounds follows from the readiness with which they form additive compounds; they yield dihydrochlorides, C^H^Cl^ tetrabromides, C^H^Br^ nitroso-chlorides, C 10 H ]6 (NOC1) 2 , nitrosites, C 10 H 16 (NO)(N0 2 ), and nitrosates, C 10 H 16 N 2 4 . These compounds are of con- siderable importance, as most of them are well-defined crystal- line compounds with definite melting-points, and can therefore be made use of in separating and identifying the various liquid terpenes. The nitroso-chlorides were first prepared by Tilden (J. C. S. 1877, 554), by the direct action of nitrosyl chloride, but are now usually obtained by Wallaces method, viz. by the action of a mixture of ethyl nitrite, acetic and hydrochloric acids on the hydrocarbon. The nitrosites are usually obtained by the action of sodium nitrite and acetic acid on the hydrocarbon, and the nitrosates by the direct addition of nitric peroxide or by the action of amyl nitrite and concentrated nitric acid. An interesting group of compounds are the nitrolamines, obtained by the action of amines (piperidine or benzylamine) on the nitroso-chlorides. They contain the NHE-group ID place of the chlorine of the nitroso-chlorides. Such com- pounds crystallize well, and can be used for identifying the various terpenes. All these reactions point to the presence (a) of a six- membered carbon ring in the monocyclic terpenes; (b) to the presence of two side chains, usually in ^-positions, one consist- ing of the CHg-group, and the second containing the grouping CX^o; (c) to the presence of two double bonds in the mole- cule. These may be both in the carbon ring, or one in the ring and one in a side chain, e.g.: CH 3 H/V II qcH 8 ) a 574 XLI. TERPENES AND CAMPHORS Fourteen such isomerides are theoretically possible. The carbon atoms are usually numbered as follows: The saturated compound C 10 H 20 , viz. p -methyl -isopropyl- hexamethylene, is called terpane*, and the compounds C 10 H 16 are terpadienes. I is A-l : 4-terpadiene, II is A-l : 4 (8)-ter- padiene, and III A-l : 8 (9)-terpadiene. The double linking in No. II between a carbon atom in the ring and a carbon of a side chain is termed a semicyclic linking. Such an unsaturated linking is quite stable under the influ- ence of heat, but in the presence of acids it wanders into the nucleus, e.g. A 4(8) ^-menthene is readily transformed into A 3 j9-menthene. A few of the terpenes contain the methyl- and isopropyl- groups in the meta positions, e.g. sylvestrene; such com- pounds are termed m-terpadienes. The nitroso-chlorides are frequently colourless, and then ap- pear to be bimolecular; some give blue solutions containing the monomolecular form. Compounds with a semicyclic linking ^>C:CR 2 yield unimolecular blue nitroso-chlorides volatile with steam. The blue compounds are true nitroso-compounds. When the NO-group becomes attached to ^>CH it usually passes over into the isonitro-group ^>C:NOH, and the com- pound becomes colourless. The following hydrocarbons belong to this group : Dipentene, A-l: 8 (9)-terpadiene or inactive limonene (see formula III; for constitution cf. B. 1895, 28, 2145; 1898, 31, 1402; 1900, 33, 1457). It occurs together with cineol in Oleum tince, and is prepared by heating pinene, camphene, sylvestrene, or limonene to 250-270 for several hours, and also by the abstraction of hydrogen chloride from its dihydrochloride. It is further produced from pinene under the influence of dilute alcoholic sulphuric acid, from terpin hydrate and terpineol by the elimination of water, by the polymerization of isoprene, and, together with the latter substance, on distilling caout- chouc. Its formation from isoprene, CH 2 : C(CH 8 ) CH : CH 2 , by heating at 300 is a synthesis, since isoprene has been synthe- sised (p. 569). It is a liquid of pleasant odour like that of oil * The name menthane is sometimes used for this hydrocarbon and menthadienea for the terpadienes. LIMONENES 575 of citron, boils at 175-176, and is more stable than pinene, although it can still be transformed into terpinene by acids. It readily forms dipentene dihydrochloride with hydrochloric acid, and with bromine a crystalline tetrabromide melting at 125. Its (inactive) nitroso-chloride yields, by the elimination of hydrogen chloride, the so-called nitroso-dipentene (inactive carvoxime), melting at 93. c?-Limonene, hesperidene, dtrene, or carvene. The oil of the orange rind consists almost entirely of dextro-limonene, which is also the chief constituent of carvene, oil of dill, oil of eri- geron, &c.; oil of citron consists mainly of d-limonene and pinene. It boils at 175, and forms a dextro-rotatory tetra- bromide, C 10 H 16 Br 4 , which melts at 104. The dextro- and laBvo-tetrabromides are identical, except that their crystals are the mirror images of one another. Dextro-limonene is very readily racemized to dipentene. /-Lunonene is present together with Isevo-pinene in the oil of fir cones. I- and d-limonenes yield nitroso-chlorides, C^H^NOCl, of corresponding rotatory powers; and, on the elimination of hydrogen chloride from these, /- and J-nitroso-limonenes, C 10 H 15 NO, which are identical with the carvoximes. The conversion of geraniol into dipentene is of considerable interest (Tiemann and Schmidt, B. 1895, 28, 2137): (CH 3 ) 2 C:CH.CH 2 .CH 2 .qCH 3 ):CH.CH 2 OH Geraniol -* (CH 3 ) 8 C(OH).CH 2 .CH 2 .CH 2 .C(CH 3 XOH).CH 2 .CH 2 OH + 2H 2 O Terpin hydrate Terpto - 2H *p*2UT Dipentene readily combines with hydrogen chloride, a dihydrochloride, C ]0 H 18 C1 2 , which melts at 50. The same compound is also formed by the action of hydrogen chloride on limonene or on pinene, and when left in contact with aqueous alcohol yields terpin hydrate, C 10 H 19 (OH) 3 (cf. formula above), in the form of large rhombic crystals melting at 117. Terpinene, probably &-l:3-terpadiene t is one of the most stable of the terpenes. It may be obtained by the action of alcoholic sulphuric acid on dipentene, or on other compounds 576 XLI. TERPENES AND CAMPHORS which yield dipentene as an intermediate product, e.g. by shaking pinene with concentrated sulphuric acid, or by boiling terpin hydrate with dilute sulphuric acid. It boils at 179- 181, is optically inactive, and most of its derivatives are oils, with the exception of the nitrosite, which melts at 155. Terpinolene, A-l:4 (8)-terpadiene, is formed when terpineol is boiled for a short time with oxalic acid solution. It boils at 183-185, and is readily transformed by acids into ter- pinene. It forms a blue nitroso-chloride. Sylvestrene, Carvestrene, A-l:8 (9)-mrterpadiene, b.-pt. 175, is the chief dextro-rotatory constituent of Swedish and Eussian oil of turpentine. It is one of the most stable of the terpenes, and gives a magnificent blue coloration with acetic anhydride and concentrated sulphuric acid. The CH 3 and C 3 H 5 substi- tuents are in the m-positions, as treatment with bromine con- verts it into T/Zrcymene. It has been synthesised from m-hydroxybenzoic acid by Perkin and Tattersall (J. C. S. 1907, 480) by reducing to its hexahydro derivative, oxidizing to y-ketohexahydrobenzoic acid, and proceeding as in the synthesis of terpineol. The constitution of dipentene is derived from its relation- ship to terpineol (p. 579), from which it is obtained by the elimination of water. If molecular rearrangement does not occur during this reaction, it is clear that dipentene must have a constitutional formula corresponding with I or II: Terpineol Formula I is not asymmetric, and therefore cannot represent the molecules of d- and Wimonenes and of dipentene; formula II, on the other hand, contains an asymmetric carbon atom, the one indicated by an asterisk, the molecule is asymmetric, and can form d- t Z-, and r-modifications. The correctness of formula II is confirmed by a study of some of the reactions of dipentene. Dipentene forms a nitroso- chloride (colourless), and this with alkalis gives the oxime of carvone. The oxime when hydrolysed yields carvone, and this on reduction yields dihy- drocarveol, a secondary alcohol formed by the addition of two PHELLANDRENES 577 atoms of hydrogen to one of the ethylene linkings and two atoms of hydrogen to the carbonyl group. Dihydrocarveol when oxidized yields a ketonic alcohol, CH 3 .C 6 H 9 (OH).CO- CH 3 , proving the presence of the C(CH 3 ) : CH 2 group in dihy- drocarveol, carvone, and dipentene. Terpinolene is also formed from terpineol by the elimina- tion of water, and should therefore be represented by formula No. I, a formula which is in harmony with the inactivity of the hydrocarbon. The stable terpinene most probably con- tains conjugate double bonds, and as it is formed from ter- pinoline by the action of acids it is probably A-l:3-terpa- diene. Phellandrene. Three isomeric phellandrenes exist in nature : d-a-phellandrene in oil of bitter fennel and in elemi oil, /-a-phel- landrene in Australian eucalyptus oil (Eucalyptus amygdalina), and d-/3-phellandrene in water dropwort (Phellandnum aqua- ticum). The d- and /-a-phellandrenes are optical antipodes, and are both &-l:5-terpadienes. The b.-pt. is 62/12 mm. It is transformed into terpinene by the action of acids, and its dibromide with alkalis yields cymene. This constitution fol- lows from the fact that nitro-a-phellandrene, when carefully reduced, yields active carvotanacetone, A-5-terpene-2-one, and has been confirmed by the synthesis of a-phellandrene from 4-isopropyl-A2-hexenone (A. 359, 285): Grignard C 3 H 7 CH<2 ! 25>CMe, dehydrated and also by its synthesis from carvone (p. 579). Carvone carvone hydrobromide * A6-terpen-2-one * IIBr reduced PC1 S 6-chloro-A-l : 5-terpadiene * a-phellandrene. reduced /3-Phellandrene is A-2 : 1 (l)-terpadiene. It has boiling-point 57/ll mm., yields two nitrosites, melting-point 97 and 102. Its constitution is based on the fact that it is oxidized by atmospheric oxygen to 4-isopropyl-A-2-hexenone (A. 343, 29), and on its synthesis from carvone (J. pr. [ii], 72, 193; 75, 141). Carvone - carvomenthol (terpane-2-ol) * A-1-terpene * reduced dehydrated bromine terpenedibromide * /?-phellandrene. ale. potash (B480) ?0 578 XLI. TERPENES AND CAMPHORS Menthene, obtained from menthol by the elimination of water, is A-3-terpene; when oxidized it yields a glycol, which on further oxidation gives /2-methyladipic acid : It has been synthesised by Wallach (B. 39, 2504) by con- densing l-methylcyclohexan-4-one with ethyl a-bromoiso- butyrate and zinc, hydrolysing and eliminating C0 2 and water. A synthetical terpene or dihydro-cymene boiling at 174 has been prepared from succinylo-succinic ester (pp. 342, 469) (B. 26, 233). It shows the complete terpene character, has a turpentine odour, becomes resinous on exposure to the air, decolorizes permanganate at once, and takes up bromine. SUMMARY OF DERIVATIVES nninn Tetra- Dihydro- xnt,it Bo^ng- bromide, chloride. Nl jj * point. M . p M _ p M.-p. Limonene... 175 104 50 Dipentene Terpinolene . . Terpinene Phellandrene. Sylvestrene... 175 125 50 183-185 116 179-181 oil oil 153 171-172 oil oil 105 175 135 72 II. Camphor Compounds. Alcohols and Ketones. Menthol, 3-terpanol, mint camphor, C 10 H 20 : The /-modification is the chief constituent of oil of pepper- mint. It melts at 43, has a strong odour of peppermint, and is used as an antiseptic and anaesthetic. When heated with copper sulphate it yields cymene, when reduced with hydriodic acid, hexahydrocymene, and on oxidation with permanganate it yields /3-methyladipic acid, and several fatty acids. As the formula contains three asymmetric carbon atoms, several stereo-isomerides are possible. The corresponding ketone menthone, 3-lerpanone, 10 H 18 O, is obtained when the alcohol is oxidized with dichromate (Beckmann, A. 1891, 262, 31), and also occurs in oil of pepper- mint. It boils at 207, and has the characteristic properties TERPINEOL 579 of a ketone; its semicarbazone melts at 184. It is readily converted into thymol (l-methyl-3-hydroxy-4-isopropyl-ben- zene) by bromination and elimination of hydrogen bromide, and when oxidized yields /?-methyladipic acid. Hence follows the constitution, which is supported by its synthesis by the distillation of calcium /?-methyl-a'-isopropylpimelate (Kotz and Schwarz, A. 357, 206): CH a CHMe CH 2 CO(X CH 2 CHMe CH 2 CH 2 .CH(C 3 H r ).COO / * " CH 2 .CH(C 3 H 7 ).CO. An unsaturated ketone pulegone, A-4 (&)-terpene-3-one, may be obtained from oil of pennyroyal. It is isomerie with ordi- nary camphor, and on reduction yields menthone. Its con- stitution follows from the fact that when heated with water it yields acetone and methylcyclohexanone. Isomerie with menthol is carvomenthol or terpane-2-ol. Carvone, A-6:8 (9)-terpadiene-2-one, is the chief constituent of oil of carraway seeds, and is widely distributed in the vegetable kingdom. It is a liquid, distils at 228, exists in d-and /-modifications, and has the properties of an unsaturated ketone (cf. A. 1897, 297, 122). With hydroxylamine it yields carvoxime, which is identical with nitroso-limonene. When heated with phosphoric acid carvone is isomerized to car- vacrol. Terpineol, &-l-terpen-8-ol, does not occur in large quantities naturally, but is obtained readily from natural products, e.g. by the action of dilute potash on limonene hydrochloride, or by the hydration of pinene hydrate. It has m.-pt. 37, b.-pt. 218, and [a] D 106. When treated with dilute acids it can give dipentene, terpinolene, terpinene, terpin hydrate, cineol or cymene, according to the conditions. Its constitution is of importance, as those of several terpenes are deduced from that of terpineol. The constitution is based on (1) examination of its decomposition products, (2) its synthesis. By means of dilute permanganate two hydroxyls are added to the double bond, and l:2:8-trihydroxyterpane (trihydroxy- hexahydro-jp-cymene) is formed, and this on further oxidation yields a ketolactone, homoterpenylic methyl ketone, which can be oxidized to acetic and terpenylic acids. The constitution of the latter has been proved to be: ,CH(CH 2 -CO 2 H).CH 2 CO CMe 2 < Q 580 XLI. TERPENES AND CAMPHORS from its method of synthesis (Simonsen, J. C. S. 1907, 184). This gives the formula,: H(CH 2 - CH 2 . CO CH 3 ) . CH 2 for homoterpenylic methyl ketone, and proves the l:2:8-posi- tions of the three hydroxyl groups in the first oxidation pro- duct, and the A-1-position of the ethylene linking and position 8 of the hydroxyl group in terpineol. Its synthesis (Perkin, J. C. S. 1904, 654) is from S-keto- hexahydrobenzoic acid (S-keto-cyclohexarie-carboxylic acid). The ester of this acid reacts with magnesium methyl iodide, and then with water, yielding: OH By the action of fuming hydrobrornic acid the hydroxyl is replaced by bromine, and then by the action of pyridine hy- drogen bromide is eliminated and A-3-tetrahydro-p-toluic acid is formed. The ethyl ester of this acid reacts with magnesium methyl iodide, and then with water, in the normal manner, yielding the tertiary alcohol, inactive terpineol: and by the elimination of water from this alcohol dipentene was obtained. This method of synthesis has been extended by Perkin and his students to a large number of cases, and they have obtained alcohols and unsaturated hydrocarbons analogous to the natural products, but which, so far, have not been obtained naturally. From A-1-tetrahydro-^-toluic acid, A-3-j?-terpen-8-ol, and A-l : 8 (9) terpadiene. From hexahydro-o-toluic acid, compounds simi- lar to terpineol and dipentene were obtained, but with the substituents in o-positions. From hexahydrobenzoic acid a compound was obtained analogous to dipentene, but without the methyl substituent in position 1. By using optically active A-1-tetrahydro-^-toluic acid, an active alcohol and ter- pene were synthesisecL (Compare J. C. S. 1905, 639, 655, 661, 1067, 1083; 1906, 8*2, 839; 1908, 573, 1871, 1876; 1910, 2129, 2147; 1911, 111, 518, 526, 727, 741.) Terpin, p-terpurl : 8-<*oJ, has been synthesised by the action COMPLEX CYCLIC TERPENES 581 of magnesium methyl iodide on both carbonyl groups of ethy cyclohexanone-4-carboxylate (Kay and Perkin, J. C. S. 1907 372), and is also formed by boiling terpineol with dilute sul- phuric acid. It exists in two stereoisomeric modifications, cis and trans. The cis is the common form, and combines with water to give terpin hydrate, C 10 H 22 3 , which forms well- developed crystals, m.-pt. 116. When dehydrated the terpins yield terpinene, terpinolene, terpineol, and cineol; the latter is an inner anhydride (ether) formed by the elimination of water from the two hydroxyl groups. C. Complex Cyclic Terpenes and Camphors The compounds belonging to this group are bicyclic, i.e. the molecule is built up of two rings. Benzene or reduced ben- zene derivatives containing a diagonal linking in the m- or p-position (examples I and II) are bicyclic, also the com- pounds which can be regarded as derived from a single ring by the introduction of a bridge consisting of one or more carbon atoms (examples III, IV, and V). For systematic nomenclature cf. Baeyer, B. 33, 3771. I. Terpenes. Pinene, C 10 H 16 , is the chief constituent of German and American oil of turpentine, oil of jumper, euca- lyptus, oil of sage, &c. It forms, together with sylvestrene and dipentene, Russian and Swedish turpentine oil. Oil of turpentine is obtained by distilling turpentine, the resin of pines, with steam, colophonium (fiddle resin) remain ing behind. It is a colourless, strongly refracting liquid of characteristic odour, almost insoluble in water, but readily soluble in alcohol and ether. It dissolves resins and caout- chouc (being therefore used for the preparation of oil paints, lakes), also sulphur, phosphorus, &c. Pinene absorbs oxygen from the air with the formation of ozone arid production o* resin, minute quantities of formic acid, cymene, &c., being formed at the same time. Dilute nitric acid gives rise eithei to terephthalic acid in addition to fatty acids, or under other conditions to terpeuylic acid (p. 579), C 8 H 12 4 (which belongs 582 XLI. TERPENES AND CAMPHORS to the fatty series). Heating with iodine transforms it into cymene, the action being violent. It acts as an antiseptic, and arrests the secretions (e.g. that of the kidneys). It exists in three stereoisomeric modifications: d-pinene or australene occurs in large quantities in German, Eussian, and Swedish oils; /-pinene or terebenthene in French turpentine oil; tW-pinene is obtained by heating pinene nitroso-chloride with aniline: []" E.-pt. d 4 T d +45 156 0-858 I 43-4 156 0-858 d-l 156 0-858 Pinene has all the characteristic properties of an unsaturated compound. It forms a nitroso-chloride (C ]0 H 16 , NOC1) 2 , colourless crystals melting at 103, which is used for isolating pinene from mixtures; also a hydrochloride, C 10 H 17 C1, a white crystalline solid melting at 131, with a camphor-like odour, hence the name "artificial camphor". This is in- soluble in water, but readily soluble in alcohol, and if hydro- gen chloride is eliminated by weak alkali, e.g. by heating it with soap or with silver acetate, camphene is obtained. It is identical with bornyl chloride, and on oxidation yields cam- phoric and apocamphoric acid. It is probable that by conver- sion into the hydrochloride an intramolecular rearrangement has taken place, as indicated by the following formulae: CMeCl CMe H 2 | ^XjHCl CMe a I H 2 C^ I CH 2 CH Pinene Intermediate Pinene Product hydrochloride The presence of a double bond in the pinene molecule is indicated by the formation of dibromides, an oil and a solid melting at 169, and also by the formation of a glycol, pinene glycol, C 10 Hi 6 (OH) 2 , by the action of dilute permanganate. The constitution of pinene is based largely upon that of pinole, CjoHjgO, a product obtained by the elimination of water from soberol, Ci H 16 (OH) 2 , which is formed when pinene is left exposed to sunlight in contact with air and water. With COMPLEX CYCLIC TERPENES * 583 dilute permanganate, pinole, which is an unsaturated ether, yields pinoleglycol, 10 H ]6 0(OH) 2 , and this on further oxida- tion yields a tetrahydric alcohol, sobrerythritol, C 10 H 16 (OH) 4 , which can be oxidized to terpenylic acid. Pinole presumably contains the same grouping of carbon atoms as terpenylic acid (see p. 579), and should be either: CH=CMe CH cf CH a dH CH 2 CMe C or Sobrerol would then be : CH= CMe CH OH I I 6Me 2 .QH I O tl-2 Oxi OJEL2 or CH 2 CMe=C-OH (*Me 2 .OH I -CH CH, but since sobrerol on further oxidation yields a tetrahydric alcohol and not a dihydroxy-ketone, formula I is correct, and the formula on p. 582 follows for pinene (Wagner). When boiled with dilute acids pinene yields terpineol or its esters; such a transformation is explicable if the assumption is made that the four-membered ring is unstable, and that a rupture between the CMe 2 and upper CH -group occurs. A similar rupture, accompanied by the wandering of a chlorine atom, occurs in the transformation of pinene nitroso-chloride into hydrochlorocarvoxime under the influence of hydrochloric acid. When pinene is oxidized with permanganate the double link ing is broken and a monobasic ketonic acid, pinonic acid, is formed, and this on further oxidation yields the dibasic acid pinic acid, from which nor pinic acid, 1:1 -dimethyl- cyclobutane-2 : 4-dicar- boxylic acid, can be obtained (Baeyer, B. 29, 1907), indicating that the four-membered ring is stable in the presence of 584 XLI. TERPENES AND CAMPHORS oxidizing agents, although readily ruptured by hydrolysing agents, e.g. pinonic acid yields when hydrolysed a lac tone, homoterpenylic methyl ketone (cf. p. 580). OH - CO C JI 2 CH>CH . CO CH 3 The only reactions of pinene difficult to account for by means of Wagner's formula are its oxidation to isoketocam- phoric acid, isocamphoronic acid, and terebic acid (Tiemann and Semmler, B. 29, 529, 3027; Perkin, Proc. 1900, 214). Bornylene is obtained by the action of alkalis on bornyl iodide (from pinene and hydrogen iodide), and as it is readily oxidized to camphoric acid it is represented by formula I. The corresponding saturated hydrocarbon camphane, CjnHjg, the parent substance of the camphor group, is obtained by reducing bornyl iodide. It melts at 154, and is optically inactive; its molecule should therefore be symmetrical. CH 2 .CMe-CH CH 2 .CMe-CO CH 2 .CMe.CO 2 H I I CMe 2 1! II I CMe 2 I III I CMe 2 CH 2 -CH CH CH 2 .CH CH 2 CH 2 .CH CO 2 H Bornylene Camphor Camphoric acid. Camphene, d and Z, is a solid, m.-pt. 50. It can be obtained from pinene by combining with hydrogen chloride, forming bornyl chloride, and then removing hydrogen chloride by means of alkalis. For some years it was represented by formula I, but it does not yield camphoric acid when oxidized. Harries and Palmer (B. 1910, 43, 1432) have shown that it forms an ozonide when its acetic -acid solution is saturated with ozone, and that this when warmed yields a mixture of camphenilone (30 per cent) (IV), CMe 2 .CH-CH 2 CMe 2 .CH.CH 2 CMe 2 .CH-CH 2 IV I CH 2 I V 6 CH 2 I VI I CH 2 I CO CH.CH 2 CO CH.CH 2 CH 2 :C - CH-CH 2 and rf-hydroxy-camphenilic acid lactone (50 per cent) (V), and they therefore suggest formula VI for camphene. The for- CAMPHORS 585 tnation of camphene from bornyl chloride must thus involve molecular rearrangements. Sabinene occurs in marjoram oil; it has b.-pt. 163-165 and [a],, -f- 80. It forms a hydrochloride and a nitroso- chloride; when oxidized it yields a ketone by the replacement of CH 2 by 0, and therefore probably contains a methylene group attached to the nucleus. It also probably contains a three-membered ring and is represented as The tri-ring is readily ruptured, as sabinene and its deriva- tives can be transformed into terpinene and related hydroxy compounds, a and /? Thujenes, C 10 H 16 (Tschugaeff, B. 34, 2279; 37, 1481), also contain a tri-ring and a double linking in positions 1 and 3 respectively. II. Camphors. The most important variety of -camphor is: Common or Japan camphor, C ]0 H 16 0, which is found in the camphor tree (Laurus camphora), and can be obtained from the latter by distillation in steam. It forms colourless, transparent, glistening prisms of characteristic odour. It melts at 175, boils at 204, has a sp. gr. 0-985, and can be sublimed readily. It is dextro-rotatory in alcoholic solution, the amount of rotation varying with the source of the camphor. When distilled with phosphoric anhydride it yields cymene; zinc chloride at high temperatures also transforms camphor into cymene, though in the latter case the reaction is less simple: C 10 H 16 = C ]0 H 14 + H 2 0. When heated with iodine it yields carvacrol, i.e. hydroxy- cymene (p. 417), just as oil of turpentine yields cymene. Nitric acid oxidizes it to the dibasic camphoric acid, C 8 H U (C0 2 H) 2 , which somewhat resembles phthalic acid (see R 23, 218), and then to camphoronic acid, unsym. trim e thy 1-carbally lie acid, &c. Camphor reacts with hydroxylamine to produce cam- phor-oxime, C ]0 H 1 (NOH), and therefore contains a carbonyl group, and with nitrous acid to produce isonitroso- camphor, C 10 H 14 0:N-OH, and thus contains the group CH 2 CO. The oxime by the loss of water is converted into the cyanide, 9 H 15 CN, which yields campholenic acid, C^I^COjH, on 686 XLt TERPENES AND CAMPHO&S saponification, and camphylamine, C 9 H 16 (CH 2 NH 2 ), on reduction (B. 21, 1125). A considerable amount of attention has been devoted by various chemists to the question of the constitution of cam- phor (Lapworth, B. A. Report, 1900, 299). At first, great im- portance was attached to the readiness with which camphor can be transformed into benzene derivatives, e.g. cymene and carvacrol, and attempts were made to represent it as a simple six-carbon ring compound, e.g. KekuU. CO whereas others represented it as a bridged six-carbon ring. In 1893 Bredt suggested the formula II (p. 584), which is now generally accepted, and which has been confirmed recently by the synthesis of camphoric acid. Bredt drew especial atten- tion to the oxidation products of camphor, namely camphoric, camphoronic, and trimethyl-succinic acid previously obtained by Koenigs. He showed that camphoronic acid when heated gave trimethyl-succinic, isobutyric, and carbonic acids and carbon, and suggested the formula C0 2 H'CH 2 -CMe(C0 2 H) CMe 2 C0 2 H, viz. a-a-j8-trimethyl-carballylic acid, a consti- tution which has since been confirmed by W. H. PerJcin and Thorpe's synthesis (J. C. S. 1897, 1169). This consists in condensing ethyl acetoacetate and ethyl a-bromo-isobuty- rate by means of zinc to ethyl /?-hydroxy-a-a-/2-trimethyl glutarate : CBrMe 2 COJ&t CMe 2 CO 2 Et CH s .CO.CH 2 .CO 2 Et ~* OH.CMe-CH 2 .CO 2 Et. The OH group is replaced by Cl, and this by ON, and the cyano-ester when hydrolysBd yields camphoronic acid : CMe 2 .C0 2 Et CN.CMe.CH 8 .C0 2 Et The relationship between camphor and its oxidation products is thus simple, as shown by the following scheme : CH 2 .CMe.CO CH 2 .CMe.C0 2 H(/S) CH 2 CMe 2 .00 2 H CMe 2 | -* CMe 2 -* I CMe 2 CH 2 .CH CH 2 CH 2 .CH CO 2 H(a) CO 2 H CO 2 H Camphor Camphoric acid Camphoronic acid. CAMPHORS 587 Camphoric acid has been synthesised by Komppa (B. 1901, 34, 2472; 1903, 36, 4332). Ethyl oxalate and ethyl /3/?-di- methyl-glutarate condense in the presence of sodic ethoxide, yielding diketo-apocamphorate : H CH CO 2 Et CO . CH C0 2 Et C CO-C CMe 2 H-CH.C0 2 Et CO.CH.C0 2 Et. This is methylated by means of sodium and methyl iodide, and the ethyl ester of diketo-camphoric acid thus obtained, >.CH.CO 2 Et CMe 2 I may be reduced with sodium amalgam to dihydroxy-camphoric acid; and this, in its turn, with phosphorus and hydriodir acid to dehydro-camphoric acid, CH.CH.CO 2 Et CMe 2 .CMe-CO,Et, which combines with hydrogen bromide; and the /3-bromo- camphoric acid thus obtained, when reduced with zinc and acetic acid, yields the racemic modification of camphoric acid. Camphor can be synthesised from camphoric acid by the following series of reactions (Holler, C. R 1896, 122, 446): I Camphoric Campholide Homocamphoric anhydride nitrile /COOH Homocamphoric acid distilled Camphor, Considerable amounts of camphor are manufactured from pinene by the following series of reactions: Pinene * Bornyl chloride Isobornyl acetate HCl Metallic acetate Isoborneol * Camphor. hydrolysed oxidised (Cf, Iloiisemann, Sci. Progress, No. 9.) 588 XLI. TERPENES AND CAMPHORS Camphoric acid is an unsymmetrical dibasic acid, as it gives two isomeric monometbyl esters and two amic acids. One carboxylic acid is probably attached to a tertiary and the other to a secondary carbon atom, as the acid yields a single monobromo substituted derivative when subjected to the Hell- Volhard-Zelinsky method of bromination. The derivatives are known respectively as a and fi (or ortho and allo), the a- methyl ester, for example, contains the group ^>CH*C0 2 Me, and the /?- methyl ester the group ^C C0 2 Me. As isonitroso- camphor C(:NOH)CO when warmed with hydrochloric acid yields a-camphoramic acid, \CH.CONH 2 , it follows that the methylene group of camphor corresponds with the a-carboxylic group in camphoric acid. Camphoric acid exists in four optically active and two racemic modifications, the latter known respectively as r-cam- phoric and r-isocamphoric acids. This points to the presence of two asymmetric carbon atoms in the molecule of the acid, as indicated in the formula. Camphor, on the other hand, exists in two active and one racemic form only. When d- camphoric acid is racemized the product is not r-camphoric acid, but a mixture of the original acid with Z-iso-camphoric acid. This is due to the fact that only one asymmetric car- bon atom is concerned in the racemization. In the oxidation of camphoric acid to camphoronic acid, camphanic acid, the lactone of a-hydroxy-camphoric acid is formed as an intei- me/3iate product; its constitution follows from the fact that it is formed by boiling bromo-camphoric anhydride with water. .C^- CO 2 H GMe 2 O Camphanic acid. 2-CMe-CO Various chloro-, bromo-, nitro-, and ammo-camphors are known. Borneol or Borneo camphor, C 10 H ir .OH, occurs in nature (in Dryobalanops camphora), and is produced by the action of nascent hydrogen upon Japan camphor: C 10 H 16 + 2H = C 10 H 18 0. It resembles the latter, but has at the same time an odour IRONE. IONONES 589 of pepper. It crystallizes in hexagonal plates, melts at 208, boils at 212, and when oxidized yields in the first instance camphor. Borneol possesses the character of a secondary alcohol, yielding esters, and with PC1 5 yields bornyl chloride, C 10 Hi 7 Cl (m.-pt. 148), which is identical with pinene hydro- chloride; bornyl chloride yields camphene when warmed with alkalis. D. Compounds related to Terpenes Irone a methyl ketone, C 13 H 20 is the odoriferous prin- ciple of the iris root, and also probably of the violet. When boiled with hydriodic acid it yields the hydrocarbon irene, GIS^IS- The formulae suggested for these compounds are : / * / CH CH-CH:CH-COMe HC CMe, ^C C CH CH 2 II -Me CH 2 CH Irone Irene (cf. Tiemann and Kriiger, B. 26, 2675). These chemists have synthesised two isomerides of irone, which they term a- and /3-ionones. . s, These also possess the odour of violets, and are employed it the present time for the manufacture of violet essence. The synthesis consists in the condensation of citral (p. 570) with acetone to form the unsaturated ketone pseudo-ionone : CMe 2 :CH.CH 2 .CH 2 .CMe:CH.CH;0 + H ? ;C = CMe 2 : CH CH 2 CH 2 CMe : CH . CH : CH COMe, which is transformed into the ring compounds a- and /2-ionones when boiled with sulphuric acid : CMe 2 CMe 2 H 2 CC.CH:CH.COMe Cll CH 2 a-Ioaone 590 XLI. TERPENES AND CAMPHORS Carone, C 10 H 16 0, is one of the most important ring ketones of the terpene series, and is formed when dihydrocarvone hydrobromide, 8-bromoterpane-2-one, is treated with alcoholic potash (Baeyer, B. 1896, 29, 5 and 2796). CHMe CHMe " nt T%I CBrMe 2 CH It is a colourless oil with an odour of camphor and pepper- mint, and boils at 210, but is, at the same time, partially transformed into the isomeric carvenone. The molecule, according to Baeyer, contains a six-carbon ring with a bridge, so that it is divided into a penta- and a tri-methylene ring. One of the most characteristic properties is the readiness with which the bridge is broken and derivatives of p- or wi-terpane are produced. Thus when heated it yields car- venone or A-3-^-terpene-2-one, with hydrobromic acid it yields 8-bromoterpane-2-one, and \vith sulphuric acid 8-hydroxy-terpane-2-one, When oxidized, carone yields a dibasic acid, caronic acid (cis and trans modifications), which Baeyer suggested was dimethyl-trimethylene dicarboxylic acid, CMe 2 < X CH-C0 2 H, a conclusion which has been confirmed by Perkin's synthesis (J. C. S. 1899, 48). In this synthesis ethyl dimethylacrylate, CMe 2 :CH.C0 2 Et, is condensed with ethyl sodio-malonate (or ethyl sodio-cyanoacetate), and the product, ethyl dimethyl- propane-tricarboxylate, (CO l2 Et) 2 CH.CMe 2 .CH 2 -C0 2 Et, when hydrolysed and heated at 200, yields ft8-dimethyl glutaric acid, C0 2 H-CH 2 .CMe 2 .CHo-C0 2 H. The a-bromo-derivative of the ethyl ester of this"acid/C0 2 Et.CHBr.CMe 2 .CH 2 .C0 2 Et > RESINS 591 yields cis and trans caronic acids when heated with alcoholic potash: CMe 2 CMe 2 CO a Et.HCBr HCH.CO.jEt * COjH-HC CH.(X) a H. XLII. RESINS; GLUCOSIDES A. Resins Many organic compounds, the terpenes in particular, possess the property of becoming " resinified " by oxidation in the air or under the influence of chemical reagents, i.e. of being con- verted into substances very similar to the resins which occur in nature. These natural resins are solid, amorphous, and generally vitreous brittle masses of conchoidal fracture, in- soluble in water and acids, but soluble in alcohol, ether, and oil of turpentine. They are found naturally in abundance, partly also as balsams, i.e. dissolved in terpenes or ethereal oils, from which they can be separated by distilling in steam. The resins dissolve in alkalis to form compounds of the nature of soap (resin soaps), being again precipitated from the aqueous solutions of these on the addition of acids; most resins must therefore consist of a mixture of somewhat complicated acids (the so-called resin-acids). Abietic acid, C 19 H 28 O 2 , has been isolated from colophonium (the residue from the distillation of turpentine); it crystallizes in small plates, melts at 153, and is soluble in hot alcohol. Pimaric acid, C 20 H S0 2 , has been prepared from galipot resin (Pinus maritima) in a similar way. It melts at 144-146, and closely resembles abiotic acid. The resins show their relation to the aromatic compounds by their conversion into hydrocarbons of the benzene or naphthalene series when distilled with zinc dust, and by the formation of di- and trihydroxy-benzenes when they are fused with potash. In addition to colophonium, there may be mentioned among other resins shellac (from East Indian Ficus varieties), and amber, a fossil resin which contains succinic acid in addition to resin-acids and a volatile oil. The resins are largely used for the manufacture of lacs, varnishes, &c. 592 XLII. RESINS; GLUCOSIDES B. Glueosides Glucoside is the name given to a number of complex organic compounds which occur in vegetable tissues. They are all characterized by the fact that on hydrolysis with acids, alkalis, or enzymes, a sugar usually ^-glucose is formed. They are therefore to be regarded as anhydro-compounds of d-glucose or some other sugar with various organic compounds. In addition to these natural glucosides, the constitutions ol which are unknown, E. Fischer has prepared artificially simplei glucosides, of the type of a- and /3-methyl-glueosides (p. 310) by the action of methyl alcohol and hydrogen chloride on glucose. These are probably stereoisomeric compounds: OCH 3 - CH[CH OH] 2 . CH CH(OH) . CH 2 . OH. The a-compound melts at 165 and the ft- at 107. They do not reduce Fehling's solution, and on hydrolysis yield ^-glucose and methyl alcohol. Among the commoner natural glucosides are: Amygdalin, C^H^C^N (p. 423), found in bitter almonds, in the leaves of the cherry laurel, in the kernels of the peach, cherry, and other Amygdalacese. It crystallizes in colourless prisms, melts at 200, is readily soluble in water, and on hy- drolysis with emulsin yields benzaldehyde, ^-glucose, and hy- drogen cyanide. Emulsin is an enzyme which occurs in bitter almonds. It is characteristic of most glucosides that in the plant tissue they are accompanied by an enzyme, which is able in the presence of water to hydrolyse them. Amygdalin may also be hydrolysed by dilute mineral acids. With concentrated hydrochloric acid it yields Z-mandelic acid, and with an enzyme contained in yeast (amygdalase) it yields glucose and /-mandelonitrile-glucoside. Isoamygdalin, obtained by the action of alkalis on amyg- dalin, is the racemic form of which ordinary amygdalin is the /-modification. Amygdalin is the commonest of the cyano- genetic glucosides, i.e. glucosides which give rise to hydrogen cyanide in plant tissues or on hydrolysis. Some of the other members are: dhurrin, p - hydroxy-mandelonitrile - glucoside (Dunstan and Henry}, in the great millet; phaseolunatin, ace- tone-cyanohydrine-a-glucoside, in beans of Phaseolus lunatus; iotusin from Lotus arabicus. Salicin, C 18 H 18 O 7 , found in varieties of Salix, is hydrolysed GLUOOSIDES 593 to saligenin (o-hydroxy-benzyl alcohol) and dextrose; populin or benzoyl-salidn, C 10 H 22 8 (in varieties of Populus), can be pre- pared artificially from benzoyl chloride and salicin. Arbutin, C 12 H 16 7 , and methyl-arbutin, C 13 H 18 7 , present in the leaves of the bear-berry, &c., yield glucose and quinol or methyl-quinol respectively. Methyl-arbutin has been syn- thesised by Michael (B. 1881, 14, 2097) from acetochloro- glucose and quinol methyl ether. Hesperidin, C 22 H 26 12 , which is contained in unripe oranges, &c., can be decomposed into glucose, hesperetic acid (isomeric with ferulic acid, p. 464), and phloroglucinol. Phloridzin, C 21 H 24 O 10 , found in the bark of fruit-trees, yields grape-sugar and phloretin, C 15 H 14 O 5 (B. 1895, 28, 1393), and this latter, in its turn, phloretic acid and phloroglucinol (p. 420). Both induce glycosuria (i.e. a functional derangement of the liver, giving rise to temporary diabetes) in animals. Aesculin, C 15 H 16 9 , present in the bark of the horse-chestnut, is decomposed by acids into grape-sugar and Aesculetin (di- hydroxy-coumarine), C 9 H 16 4 . Digitonin, digitalin, and digitalei'n are three glucosides which, together with digitoxin (the most important constituent from a pharmacological point of view), are present in the digi- talis of commerce (cf. B. 24, 339; 25, Ref. 680; 31, 2454). Coniferin, C 16 H 22 8 + 2H 2 0, contained in the cambium sap of the Coniferae, yields glucose and coniferyl alcohol on hy- drolysis, and serves for the preparation of vanillin (p. 430). Indican (p. 526) is indoxyl-glucoside. Syringin, the glucoside of Syringa, is a methoxy-coniferin. Myronic acid, C 10 Hi 7 9 NS 2 , is present as potassium salt (Sinigrin), C^H^KOgNS* H 2 (glistening needles), in black mustard seed. It is hydrolysed by baryta water, or by my- rosin, an enzyme present in mustard seed, to grape-sugar, potassium bisulphate, and allyl isothiocyanate (p. 277). (For list of natural glucosides cf. Armstrong, " Simple Carbo- hydrates and Glucosides ", p. 80.) XLIII. ALBUMINS; PHYSIOLOGICAL CHEMISTRY An extended description of the substances (other than those already mentioned) which are found in the animal organism, and which are therefore of importance for physiological chemistry, (BttO) * 594 XLIII. ALBUMINS; PHYSIOLOGICAL CHEMISTRY will not be attempted here, since they are for the most part better known from a physiological than from a chemical point of view. Only the albumins and some of the substances which are produced during metabolic processes will be dealt with. Albumins For an account of the modern views of the chemistry of albumins see A. Kossel (B. 1901, 34, 3214; E. Fischer, B. 1906, 39, 530). The albumins make up the chief part of the organism, being present partly in the soluble and partly in the solid state; they are found in protoplasm and in all the nutritive fluids of the body. In the tissues of green plants the albumins are synthesised in quite unknown ways from simple substances like carbon dioxide, water, ammonium nitrate and sulphate. (Cf. Meldola, J. C. S. 1906, 749.) The majority of albumins are insoluble in water, but dissolve in dilute saline solutions. Their presence in the juices of the animal organism is prob- ably due to saline and other substances. In solution they are opalescent, laevo-rotatory, and do not diffuse through parch- ment paper, i.e. are colloids; but they are thrown down when the solution is warmed, or upon the addition of strong mineral acids, of many metallic salts [e.g. copper sulphate, basic lead acetate, and mercuric chloride], of alcohol, tannic acid, acetic acid together with a little potassium ferrocyanide, picric acid, or phosphotungstic acid. They are insoluble in alcohol or ether, and their solutions are usually precipitated ("salted out") by the addition of ammonium sulphate, and mixtures of different albumins can often be fractionally pre- cipitated by gradually increasing the concentration of the ammonium sulphate. This concentration is definite for each albumin, as is also its temperature of coagulation. Proteins can also be coagulated by treatment with absolute alcohol or with boiling water. After coagulation all albumins become insoluble in neutral solvents, but dissolve in alkalis or acids, yielding metaproteins, which are also formed by boiling the uncoagulated albumins with acetic acid or alkali. When boiled: (a) with nitric acid, they are coloured yellow (the xantho- protein reaction); (b) with a solution of mercuric nitrate containing nitrous acid (Milloris reagent), red; (c) with caustic soda solution and a very little cupric sulphate, violet. Many of the albumins have been prepared pure, although ALBUMINS 595 this is a very difficult operation. With the exception of the crystalline albumin which occurs in hemp, castor -oil, and pumpkin seeds (B. 15, 953), and the recently isolated crystal- line egg albumin and serum albumin (B. 24, Ref. 469; 25, Ref. 173), they do not crystallize. The different albumins vary only slightly among themselves in percentage composition; they contain: C = 52-7 to 54-5 p.c.; H = 6'9 to 7'3 p.c.; N = 16'4 to 17'6 p.c.; O = 20*9 to 23'5 p.c. ; and S = 0'8 to 5'0 p.c. It is impossible at present to construct a formula from these numbers, and even approximate molecular weights have not been determined. The fact that albumin contains sulphur is worthy of note, though the mode in which it is combined in the molecule is unknown; warming with a dilute alkaline solution is sufficient to eliminate it partially, e.g. when white of egg is boiled with an alkaline solution of lead oxide, sulphide of lead is precipi- tated (the test for sulphur in albumin). Albumin preparations usually leave a very considerable amount of ash, i.e. inorganic salts, on incineration. It is not yet certain in how far this mineral matter forms an integral constituent of these substances; but the properties of "egg albumin free from ash " are materially different from those of ordinary albumin (B. 25, 204). Although the constitution of no single albumin has been determined, a considerable amount of work has been done in this direction, more especially by an examination of the simpler products obtained when the albumins are (a) oxidized, (b) hydrolysed, and (c) fermented by micro-organisms. (a) The products obtained on oxidation consist largely of volatile fatty acids, their aldehydes, ketones, and nitriles, together with hydrogen cyanide and benzoic acid. (b) The usual hydrolytic agents used are (1) baryta water, (2) hydriodic acid, (3) concentrated hydrochloric acid, and (4) sulphuric acid (25 per cent). The last of these appears to be the best, as it produces less complex decomposition, e.g. less ammonia and more amino- acids. The most marked feature of the products thus obtained is the predominance of amino-acids. The list of compounds which have been isolated from the hydrolytic products is as follows: (i) Ammonia; (ii) car- bamide; (iii) diamino-acids; (iv) monamino-acids; (v) pyr- 596 XUII. ALBUMINS; PHYSIOLOGICAL CHEMISTRY rolidine - 2 - carboxylic acid (proline), HN< 2 , M^ii(L'U 2 il) Url 2 and its hydroxy derivative (oxyproline) ; (vi) furaldehyde (p. 517); (vii) histidine (iminazole-alanine), C G H 9 2 Ng; (viii) arginine, or 8-guanino-a-amino valeric acid, NH 2 C( : NH) NH CH 2 .CH 2 .CH 2 .CH(NH 2 ).C0 2 H, which has been synthesised from ornithine (p. 465) and cyanamide (p. 277); (ix) trypto- phan (indol-alanine); (x) tyrosine (p. 459). Of the diamino-acids the following are the more important: Diamino- acetic acid from casein, a8-diamino-valeric acid or ornithine, ac-diamino-T^caproic acid or lysine. Of the monamino-acids : Glycocoll, and derivatives such as skatolglycocoll, a-amino-propionic acid or alanine, a-amino- isobutylacetic acid or leucine, a-amino-isovaleric acid or valine, a-amino-succinic or aspartic acid, a-amino-glutaric or glutamic acid, phenylalanine or /?-phenyl-a-amino-propionic acid, CH 2 Ph CH(NH 2 ) C0 2 H, a-amino-a-hydroxy-propionic acid or serine, a-amino-a-thiolactic acid or cystein, and the corre- sponding disulphide or cystin, /?-hydroxy-phenyl-a-amino-pro- pionic acid. Certain albumins also yield carbohydrates, more especially amino-sugars, e.g. glucosamine, C 6 H n 5 NH 2 (B. 1895, 28, 3082). A simple method for the separation and isolation of many of these amino-acids from the products of hydrolysis is due to E. Fischer. He converts the acids into esters by the hydrogen- chloride method, and then separates these by fractional dis- tillation under reduced pressure. A few simple proteins yield only a single ammo-derivative; thus both salmine and clupeine, obtained respectively from the testicles of the salmon and herring, yield very little besides histidine. As a rule, the more complex proteins yield a considerable number of amino-compounds, the number of such compounds and also their relative proportions varying with the protein. A glance at the list of above products indicates that the albumin molecule is largely built up of aliphatic groups. The carboxylic groups present in the hydrolytic products are probably not present in the original molecule, and it is highly probable that most of the amino-groups are not present as such, but are employed in uniting the various radicals together, since only some 10 per cent of the total nitrogen in ALBUMINS 597 albumin is eliminated as such on treatment with nitrous acid ; in other words, the amino-group of one molecule reacts with the carboxylic group of another, yielding compounds with the group, CO'NH', characteristic of acid amides. Emil Fischer and others have synthesised complex compounds of this type by the gradual condensation of amino-acids. Although none of the proteins has been so far synthesised, the products the polypeptides exhibit considerable analogy to the peptones. The following general methods are used for the synthesis of polypeptides : 1. The chloride of a halogenated fatty acid is condensed with the ester of an amino-acid, the resulting ester hydrolysed, and the halogen then replaced by an amino-group by means of ammonia: Cn 3 .CHBr.COCl CH 8 -CHBr.CO.NH.CH 2 .C0 2 Et CH 3 .CH(NH a ).CO. Alanylglycine. 2. The dipeptide thus obtained can be converted into its acid chloride, and this condensed with a molecule of an ester of an amino-acid, e.g. glycine ester, yielding the compound CH 3 .CH(NH 2 ).CO.NH.CH 2 .CO.NH.CH 2 .C0 2 C 2 H 5 , which on careful hydrolysis yields the corresponding acid alanyl- glycylglycine an example of a tripeptide. The operations can be repeated, and in this way compounds containing 18 amino-acid residues have been synthesised, one of which has a molecular weight 1213. As the amino-acids obtained by hydrolysing natural pro- teins are optically active, Fischer used optically active acids and esters in his synthetical operations, the optically active acid being obtained by resolving its racemic benzoyl derivative by means of active bases and then removing the benzoyl group. 3. A modification of the above synthesis consists in con- verting an amino-acid into its acid chloride by means of acetyl chloride and phosphorus pentachloride, and then con- densing this chloride with a molecule of an amino-acid. 4. Glycylglycine can be obtained by heating ethylglycine when the anhydride diketopiperazine, NHQjj'^Q^NH, is formed, and hydrolysing this with dilute alkali. A few polypeptides, e.g. tetrapeptides, have been isolated from the hydrolytic products of certain proteiiw. 598 XLIII. ALBUMINS; PHYSIOLOGICAL CHEMISTRY Kutscher has shown that many albumins can combine to- gether to give complex substances, and it is probable that many natural albumins are complexes formed by union of simpler molecules. (c) The putrefaction of albumins gives rise not only to amino- acids, but also to other aromatic and fatty acids (e.g. butyric acid, phenyl-acetic acid), indole, skatole, and cresol; further, to the alkaloid-like ptomaines (the toxines or poisonous alka- loids produced in dead bodies), of which tetramethylene- diamine, or " putrescine ", and pentamethylene-diamine, or " cadaverine ", B. 19, 2585, have been isolated (cf. p. 196). For a compilation of the ptomaines, see Brieger, Archiv. f. patholog. Anatomic, 115, 483. Albuminous matters undergo change when acted upon by the juices of the stomach at a temperature of 30-40, the enzyme pepsin converting them in the first instance into anti- and hemi-albumoses, both of which then pass into peptone; trypsin, an enzyme of the pancreas, likewise gives rise to the two above albumoses, but then transforms the anti-compound into peptone and the hemi-compound into leucine, tyrosine, aspartic acid and glutamic acid (the pancreatic digestion; for details, see Kuhne, B. 17, Kef. 79). The peptones are readily soluble in water, diffuse quickly through vegetable parchment, and they are neither coagulated upon heating nor by most of the reagents which coagulate albumin, e.g. ammonium sulphate, whereas the albumoses are precipitated by this reagent. These reactions indicate that the albumoses are intermediate between the albumins proper and the simple decomposition products already mentioned, and that the peptones are intermediate between the same decomposition products and the albumoses. Both albumoses and peptone possess acidic and basic properties, and may be esterified by means of alcohol and hydric chloride, hence they probably contain carboxylic groups. The different albumoses, e.g. hetero- and proto-albumoses, must differ considerably as regards constitution, as the former yields glycocoll, much arginine, but little histidine, and very little tyrosine and indole on hydrolysis, whereas the latter yields no glycocoll, equal amount of arginine and histidine, and much tyrosine and indole. Other methods adopted are to introduce chemical substances into the animal system intravenously or per os, and then to examine in what form the compound is excreted from the ALBUMINS 599 system; as examples, bromobenzene is excreted as bromo- phenyl-mercapturic acid, and various terpene derivatives are excreted in combination with glycuronic acid. When soluble salts of iron are allowed to act upon white of egg and upon peptone, iron albuminate and iron peptonate are respectively produced, these being employed in medicine as iron preparations for internal use under the names of liquor ferri albuminati and peptonati. The following scheme of nomenclature for proteins is ac- cepted by most English-speaking chemical and physiological societies : 1. Protamines. The simplest proteins, they include sal- mine, sturine, &c., isolated from fish testicles. 2. Histones. These are somewhat more complex than the protamines. They can be precipitated by ammonia. 3. Albumins, e.g. egg albumin, serum albumin from blood and nutritive fluids, and lact- albumin from milk. These are crystalline, dissolve in water, and are not precipitated by common salt. They coagulate at 70-75. 4. Globulins are insoluble in water but dissolve in dilute salt solution. They can be salted out by means of magnesium sul- phate. Examples : Globulin from the crystalline lens of the eye, nbrinogen from blood, fibrin from clotted blood, and myosin from the plasma of living muscle, are globulin derivatives. 5. Gluteins are proteins of vegetable origin. They are soluble in alkalis, and are closely allied to the globulins. 6. Gliadins. Vegetable proteins, soluble in alcohol. 7. Phospho-proteins, e.g. caseinogen, the principal protein of milk; casein obtained from caseinogen by the action of rennet. They are acidic and do not coagulate. 8. Sclero -proteins. Mainly insoluble proteins, which form the skeletal parts of tissues, e.g. gelatin from cartilages, chon- drin, elastin from ligaments, and keratin from hoofs, nails, hair, &c. Sponge and coral contain similar substances. 9. Conjugated proteins consist of compounds containing a protein molecule united to some other group. (a) Nucleo -proteins are important constituents of the cell nucleus, e.g. of pus cells, blood corpuscles, and yeast cells. They are insoluble in water or acids, but dissolve in alkalis, and contain combined phosphoric acid. On hydrolysis they yield albumin and nucleic acid, and on further hydrolysis the nuclein bases, viz. adenine, hypoxan thine, guanine, and xanthine (p. 292). 600 XLIII. ALBUMINS; PHYSIOLOGICAL CHEMISTRY Certain varieties of nuclein are free from sulphur, while others contain it; the latter group yield tyrosine when de- composed. The product which is obtained when the albumin of hens' eggs is coagulated by meta-phosphoric acid resembles nuclein. Nucleic acid may also be transformed into nuclein bases by various enzymes present in the different organs of the animal system. Recent work renders it highly probable that at least three distinct enzymes take part in such transformations: (a) an oxidase; (b) adenase, which transforms adenine into hypoxanthine and xanthine; (c) guanase, which transforms guanine into xanthine. (b) Chroma-proteins or Haemoglobins. Haemoglobin is the colouring matter of the red blood corpuscles. It can be de- composed into globin and hsematin (see below). Haemoglobin combines very readily with oxygen, e.g. in the lungs, to oxy- haemoglobin, which yields up its oxygen again, not only in the organism, but also in a vacuum and when exposed to the action of reducing agents, e.g. ammonium sulphide. With car- bon monoxide it combines to the compound, carbon monoxide- hsemoglobin. All three compounds can be obtained crystal- lize* in the cold, and they possess characteristic absorption spectra. Hsemin, C 84 H3 2 4 N 4 FeCl, is obtained in the form of characteristic microscopic, reddish-brown crystals by the action of glacial acetic acid and some common salt upon oxy-hsemo- globin; this is a delicate test for the presence of blood. Hsematin, a dark-brown powder containing 8 per cent of iron, is obtained by the spontaneous decomposition of haemoglobin, or by the action of alkalis on hsemin, and contains' OH in place of the Cl atom of hsemin (cf. Piloty and Eppinger, A. 377, 341). (c) Gluco-proteins. The mucins yield albumin and carbo- hydrate on hydrolysis; they are insoluble in water, but possess acidic properties. The percentage of nitrogen is less than in the ordinary albumins. 10. Protein derivatives, or the products of protein hy- drolysis. (a) Meta-proteins. This includes the substances previously known as alkali-albumins and acid-albumins, (b) Froteoses, including albumoses, globuloses, and gelatoses. (c) Peptones (cf. p. 598). (d) Polypeptides (cf. p. 597). REDACTION WITH NASCENT HYDROGEN 601 XLIV. REDUCTION Reduction is the name usually given to a reaction in which oxygen is withdrawn from or hydrogen added to a compound; in certain cases both of these processes occur. Numerous cases of reduction have been mentioned in the preceding chapters, as examples: (C 6 H 6 ) 2 'N 2 0, azoxy -benzene, * (C 6 H 5 ) 2 N 2 , azo-benzene (p. 397); (CH 3 ) 2 .CO, acetone, > (CH 3 ) 2 .CH.OH, iso-propyl alcohol (P. 72); nitre-benzene, - C 6 H 6 NH2, aniline (p. 372). As the reaction is so general, a more detailed discussion of it is given in this chapter. In addition to the above reactions, viz. withdrawal of oxygen or addition of hydrogen, the process previously referred to as inverse substitution (p. 33) the replacement of halogen by hydrogen, e.g. C 2 H 5 I - C 2 H 6 is usually re- garded as a type of reduction. A. Nascent Hydrogen. Of the numerous methods that can be employed for reduction, one of the commonest is by means of nascent hydrogen, i.e. hydrogen generated in the presence of the substance to be reduced. The fact that the majority of these reductions cannot be effected by means of ordinary gaseous hydrogen, but can be readily attained by the use of hydrogen at its moment of formation, is used as an argument in favour of the view that nascent hydrogen consists of the free atoms. As nascent hydrogen can be produced in a variety of ways, it follows that reductions by this method can be conducted under very varying conditions; and it is of extreme importance to note that the conditions are a prime factor in determining the nature of the product. It has already been pointed out that the reduction of nitro-benzene can give rise to azoxy-benzene, azo-benzene, phenyl-hydroxyl- amine, or aniline, according to the conditions under which the reaction occurs; and similar phenomena have been mentioned in the case of the reduction of terephthalic acid (p. 468). Reductions by means of nascent hydrogen may take place in acid, alkaline, or neutral solution, and this affords a simple method of classification for these reactions. (a) Reduction in Acid Solution. Almost any combination of acid and metal which gives rise to nascent hydrogen may be employed for this purpose; but the usual combinations are XLIV. REDUCTION tin and hydrochloric acid, zinc and hydrochloric acid, zinc and acetic acid, zinc dust and acetic acid, iron and acetic acid. The usual method employed in the laboratory for the reduction of iiitro-compounds to the corresponding ammo- compounds (see Aniline) is by means of tin and hydrochloric acid. The metal is first converted into stannous, and then into stannic chloride : Sn + 2HCl = SnCl 2 + 2H; SnCL + 2HCl = SnCl 4 + 2H; C 6 H 5 N0 2 + 6H = C 6 H 5 .NH 2 + 2H 2 0; or C 6 H 4 (N0 2 ) 2 + 12H = C 6 H 4 (NH 2 ) 2 + 4H 2 O. The method has certain objectionable features which render it unsuitable for use on the manufacturing scale. Among these may be mentioned (a) need for large excess of concen- trated acid, and the fact that this acid will subsequently have to be neutralized, (b) The strong acid is liable to react with the reduction product, yielding halogenated amines. The in- troduction of the halogen into the benzene nucleus probably occurs in the following manner: C 6 H 6 .N0 2 C 6 H 6 .NH-OH C 6 H 6 .NHC1 -> C1.C 6 H 4 .NH 2 (Bamberger). Such chlorinated amines are always liable to be formed when concentrated hydrochloric acid is used in com- bination with a metal for the reduction of nitro-compounds. (c) The reduced compound often combines with the stannic chloride to form a double salt, e.g. C 6 H 5 NH 2 , HC1, SnCl 4 , and certain of these are somewhat difficult to decompose. Aliphatic nitro-derivatives may also be reduced to amines by this method, except in cases where two nitro-groups are attached to the same carbon atom, when a ketone is formed. Other examples are the conversion of cyclic derivatives into hydro-derivatives, e.g. jp-hydroxy-quinoline to tetrahydro-jp- hydroxy-quinoline, and of sulphonic chlorides, R-S0 2 'C1, into thio-phenols, R'SH. In many cases tin-foil is stated to be preferable to granu- lated tin, as it exposes a larger surface, and occasionally alcoholic solutions of the hydrogen chloride are used in place of aqueous. Stannous chloride and hydrochloric acid occa- sionally give better yields than tin and acid; thus nitro- methane is reduced to methyl-hydroxylamine, and the method has been recommended for the estimation of nitro-groups. An excess of standard stannous chloride solution is used, and REDUCTION WITH NASCENT HYDROGEN 603 the excess titrated after the reduction is complete, each nitro- group requiring 3 gram molecules of stannous chloride. Stannous chloride is sometimes used without the addition of free acid; thus Witt, by reducing amino-azo-benzene with alcoholic stannous chloride, obtained aniline and ^-phenylene- diamine : C c H 5 -N:N.C 6 H 4 .NH 2 -f 4H = C 6 H 5 -NH 2 + NH 2 .C 6 H 4 .NH 2 . (Compare also Jacobson, A. 1895, 287, 100.) Most of the objections referred to in connection with the reduction of nitre-derivatives by means of tin and hydro- chloric acid may be avoided by using iron and acetic acid or dilute hydrochloric acid. This method is usually adopted on the manufacturing scale, as only a small amount of acid, some one-fortieth of that indicated by the equation, C 6 H 5 N0 2 + 3Fe + 6HC1 = C 6 H 5 .NH 2 + 3FeCl 2 + 2H 2 O, is required. The reason for this may be that the ferrous chloride reacts with the aniline and water, yielding ferrous hydroxide and aniline hydrochloride : 2C 6 H 6 NH 2 -f 2H 2 = Fe(OH) 2 + 2C 6 H 5 N The hydrochloride then reacts with more iron, producing ferrous chloride and nascent hydrogen, which can reduce more of the nitro-compound. The iron method possesses further advantages, as r the reduction can be regulated much more readily than in the case of tin and acid. Thus ^?-nitro-acetanilide reduced by the iron method gives the corresponding ammo-compound, NH 2 .C 6 H 4 .NH.CO-CH 3 , whereas with tin and hydrochloric acid hydrolysis and reduction both occur, and the product is jp-phenylene-diamine. Iron and acid may also be employed for the reduction of aromatic polynitro-compounds to amino-nitro-derivatives : C 6 H 4 (N0 2 ) 2 but such a reduction is almost impossible with tin and acid. Zinc, as granulated zinc, or more frequently as zinc dust, is also used in conjunction with acids, usually hydrochloric or acetic. When concentrated hydrochloric is employed, chlorine is apt to enter the benzene ring (cf. p. 602); with glacial acetic acid (Kra/ts, B. 1883, 16, 1715) acetyl derivatives are formed occasionally instead of the simple reduction products. For 604 3tLlV. REDACTION example, when aldehydes are reduced, alkyl acetates and not alcohols are formed: K-CHO + 2H + CH 3 .C0 2 H = R-CH^O-CO-CH, and when nitro-derivatives are reduced, acetylated amines are obtained. Although aliphatic ketones cannot be reduced by this method, all ketones containing one or two benzene nuclei directly attached to the carbonyl group are readily reduced to pinacones (p. 191). Hydroxy-derivatives of anthraquinone may also be reduced in a similar manner, one or more of the hydroxy- groups being replaced by hydrogen, and aliphatic nitro-derivatives, such as nitro-guanidine, NH:C(NH 2 )NH- N0 2 , may be reduced to the corresponding amino-compounds. A transformation occasionally effected by means of zinc dust and glacial acetic acid is the removal of two atoms of halogen and the conversion of a saturated compound into an olefine, e.g. tetramethyl-ethylene dibromide into tetramethyl-ethylene : CMe 2 Br-CMe 2 Br + 2H = 2HBr -f CMe 2 :CMe 2 . All peroxides (p. 181) are readily reduced by this method, e.g. diethyl-peroxide, Et 2 2 , to ethyl alcohol (or ethyl acetate). Dilute acetic acid is frequently used with zinc dust. This is the usual method adopted for the reduction of osones to ketoses (Fischer) (p. 304): K.CO.CHO + 2H = B.CO.CH 2 .OH. It is also extremely useful in the preparation of hydrazines from nitrosamines and nitramines, e.g. Fischer (A. 1886, 236, 198) obtained methyl-phenyl-hydrazine, NPhMeNH 2 , by the reduction of methyl-phenyl-nitrosamine, NPhMe-NO. Other reducing agents, e.g. metal and concentrated hydrochloric acid, stannous chloride, zinc dust and alkali, are all liable to carry the reduction a stage further and yield a mixture of ammonia and amine: NPhMe.NH 2 + 2H = NHPhMe + NH 3 . An extremely interesting example of the influence of the reducing agent and the method of reduction on the nature of the final product is met with in the case of nitro-benzyl- phenyl-nitrosamine, N0 2 C 6 H 4 CH 2 NPh NO. With tin and hydrochloric acid it yields phenyl-indazole, M >NPh; c H <L> REDUCTION WITH NASCENT HYDROGEN 605 with sodium amalgam in alkaline solution, o-amino-benzyl- aniline, NH 2 - C 6 H 4 CH 2 NHPh, and ammonia; and with zinc dust and glacial acetic acid, o-amino-benzyl-phenyl-hydrazine, NH 2 .C 6 H 4 .CH 2 .NPh.NH 2 . (Busch, B. 1894, 27, 2899.) With zinc dust and dilute sulphuric acid the reaction is somewhat slower than with acetic acid; with these reagents sulphonic chlorides may be transformed into thio-phenols, or the reaction may proceed a stage further and the sulphur be completely removed. Zinc dust and concentrated sulphuric acid are occasionally used for the reduction of nitro-compounds, and in all cases the pro- duct is an amino-hydroxy- and not a simple amino-derivative : C 6 H 6 .N0 2 jE>-NH 2 .C 6 H 4 .OH; -* NH 2 .C 6 H 3 (OH).C0 2 H. Lassar-Cohn attributes this to the oxidizing action of the concentrated sulphuric acid, whereas it is probable that reduction to a phenyl-hydroxylamine first occurs; and this, in the presence of the concentrated acid, undergoes intra- molecular rearrangement, yielding the amino-phenol (cf.p.397): C 6 H 5 .N0 2 C 6 H 6 .NH.OH OH.C 6 H 4 .NH 2 . When zinc or zinc dust and any acid are added to the nitrate of an aromatic amine, a diazonium salt is formed: C 6 H a .NH2,HN0 3 -f Zn-f 3HC1 = ZnCl 2 -f C 6 H 5 N 2 C1 -f 3H 2 0. Sodium amalgam is sometimes used as a reducing agent in the presence of acid; thus with acetic acid it is used for the reduction of hydrazones to primary amines : Reductions by means of sodium amalgam and dilute sulphuric acid have been largely used by E. Fischer in his synthetical work on the sugars, since the lactones of hydroxy-acids when reduced in this way at yield aldoses (pp. 304, 305) : X.CH.CH(OH).CH(OH).CO-*X.CH(OH).CH(OH).CH(OH).CH:0. I _ _ I The same reducing agents convert phloroglucinol, s-C 6 H 3 (OH) 8 , into its hexahydro-derivative. A very common acid reducing agent is hydriodic acid, its reducing action being attributed to the decomposition of the hydrogen iodide into iodine and nascent hydrogen at moderate temperatures. The method was first introduced by Berthelot, 606 XLIV. REDUCTION who, in his earlier experiments, used the acid alone; but when he found that the liberated iodine interfered with the reduc- tion by giving rise to iodo-derivatives or by oxidizing, he added red phosphorus or sometimes phosphonium iodide. The function of the phosphorus is to combine with the iodine immediately it is liberated from the hydrogen iodide, and thus form phosphorus tri-iodide, which is then decomposed by the water present, yielding hydrogen iodide and phosphorous acid. Phosphonium iodide is often formed as a by-product in these reductions. It has been shown that with hydriodic acid alone practically all oxygen compounds are reduced to satu- rated hydrocarbons at a temperature of 275, the reduction being conducted in sealed cubes, e.g. glycerol yields propane. Amines are also transformed into paraffins, e.g. methylamine yields methane. When hydriodic acid and phosphorus are used, the reduction can either take place in open vessels, e.g. a flask with reflux condenser, or in sealed tubes if a higher temperature is required As examples of the former we have the following : CHI 3 CHJL; anthraquinone * dihydro-anthracene ; benzilic acid, OH.CPh 2 .G0 2 H diphenyl-acetic acid, CHPtyC0 2 H; tri- hydroxy-glutaric acid, COJ! . [CH . OH] 3 . C0 2 H glutaric acid; mixed ketones, e.g. C 6 H 5 CO CH 3 * hydrocarbons. As examples of the latter we have the conversion of fatty acids, from C 8 H ir C0 2 H upwards, into paraffin-hydrocarbons, the reduction of anthracene to hydro-anthracenes, and of hydroxy - hexamethylene carboxylic acid, OH C 6 H 10 C0 2 H, to hexahydro-benzoic acid, C 6 H n C0 2 H. It is interesting to note that hydriodic acid is not a good reducing agent for nitre-compounds ; as a rule it leaves the nitro- group intact, e.g. nitro - benzene - sulphonic chloride, N0 2 .C 6 H 4 .S0 2 C1, yields first N0 2 .9 6 H 4 .SO.SO.C 6 H 4 .N0 2 , and ultimately m-dinitro-diphenyl-disulphide, N0 2 -C 6 H 4 S S.C 6 H 4 .N0 2 . (b) Nascent Hydrogen in Alkaline Solution. There are various methods of reducing with nascent hydrogen in al- kaline solution; one of the commonest is the addition of metallic sodium, in the form of wire or thin strips, to boiling ethyl alcohol; as a rule it is necessary to use absolute alcohol* as the presence of water diminishes the yields. As examples, we have the reduction of nitriles to primary amines, RCN *R.CH 2 -NH 2 (p. 106), of esters to alcohols (p. 72), of naph- thalene to dihydro-naphthalene, of pyridine to piperidine (p. 537), REDUCTION WITH NASCENT HYDROGEN 607 although quinoline is not so readily converted by this process into tetrahydro-quinoline, and lastly, of various benzene deriva- tives, e.g. w-hydroxy- benzoic acids into corresponding hexa- hydro-derivatives, i.e. derivatives of hexamethylene. When a higher temperature is required than can be attained with ethyl alcohol, boiling amyl alcohol is used (Bamberger). By this method naphthalene and its derivatives may be converted into their tetrahydro-compounds, e.g. the naphthols, C 10 H 7 'OH, into tetrahydro-naphthols, C 10 H n OH. It is interesting to note that the chief reduction product obtained from a-naphthylamine is ar-tetrahydro-a-naphthyla- mine (I), and from /3-naphthylamine a mixture of ar- and ac- tetrahydro-derivatives (II and III): H 2 NH 2 H 2 H Similarly phenanthrene is reduced to its tetrahydro-deriva- tive, anthracene to its dihydro-compound, and the benzene carboxylic acids to di-, tetra-, or hexahydro-derivatives, accord- ing to the temperature and other conditions of reduction (cf. p. 467); with sodium and boiling amyl alcohol, benzoic acid yields mainly C 6 H n C0 2 H. In a few cases, when sub- stituted benzoic acids are reduced by this method, a rupture of the ring occurs and an aliphatic acid is formed. One of the best-known examples is the reduction of salicylic acid to pimelic acid (p. 344); in this case it may be assumed that a tetra- hydro-salicylic acid is first formed, and that by the addition of the elements of water this is converted into pimelic acid : < xCH 2 .C(C0 2 HK G O H \CH 2 CH 2 - -/^ C Although aniline cannot be converted into its hydro-deriva- tives by this method, aniline-o-sulphonic acid yields a hexa- hydro-derivative. In place of alcohol moist ether is sometimes used in conjunction with sodium. This is generally accom- plished by adding the metal to ether floating on water, or better, on a solution of sodic bicarbonate. Dibenzyl ketone can thus be reduced to dibenzyl-carbinol, mesityl oxide to 608 XLIV. REDUCTION methyl-isobutyl-carbinol, and acid chlorides, ECOC1, to the corresponding alcohols, BCH 2 OH. Sodium amalgam may be used in place of sodium itself, as a rule in combination with water; the amalgam is added gradually and the mixture kept agitated, and a small amount of alcohol is added, if necessary, to prevent frothing. By this method, benzene and its derivatives may be reduced to di- and tetrahydro-compounds. Many olefine derivatives are reduced to saturated compounds, e.g. cinnamic acid, CgH 5 CH:CH' C0 2 H, to phenyl-propionic acid, C 6 H5.CH 2 .CH 2 .C0 2 H, and ketones to secondary alcohols. Alcohol is occasionally a better medium than water, and by this method azo- may be reduced to hydrazo-compounds (p. 395), and benzaldehyde and its substituted derivatives into benzyl alcohols. In many instances the alkali formed by the action of the metal on water or alcohol has a deleterious action on the pro- ducts of reduction, and it becomes necessary to neutralize the alkali as far as possible. This may be effected by the occasional addition of mineral acid, but is most readily accomplished by Aschan's method of leading carbon dioxide through the liquid as the reduction proceeds, and in this way converting the sodium hydroxide into bicarbonate as fast as formed. It is the method often used in the reduction of phthalic acids, &c., and may also be employed for converting naphthalene and resorcinol into their dihydro-derivatives, and benzoic acid into Zinc and alkali are often used to reduce aromatic ketones to secondary alcohols, e.g. (CgH^CO -* (C 6 H 5 ) 2 CH.OH; whereas when zinc and acetic acid are used, the corresponding pinacpnes, (C 6 H 5 ) 2 C(OH) C(OH)(C 6 H 5 ) 2 , are formed. Alkali, especially sodic hydroxide, may be used with zinc dust; the usual method being to keep the alkali and substance well stirred, and to add the zinc dust gradually. As examples we have: Anthraquinone - anthranol ; fatty diazo-compounds * hydrazo-compounds; o - nitraniline * o-phenylene-diamine. Further examples are the dehalogenating of aromatic compounds and the preparation of azoxy- and azo-compounds (p. 397). (c) Nascent Hydrogen in Neutral Solution. Many reduc- tions take place most readily in the absence of free acid or free alkali, and may be effected by the following reagents : (i) Zinc filings or granulated zinc and alcohol, e.g. /?-bromo-allo-cinnamic acid * allo-cinnamic acid (p. 454); (ii) Gladstone-Tribe couple, in the reduction of alkyl haloids to paraffins (p. 33); (iii) mix- REDUCTION WITH METALS 609 ture of zinc and iron, in the presence of certain metallic salts, e.g. acetone * isopropyl alcohol; (iv) zinc dust and water (or alcohol), which may be used for reducing azo-dyes to mixtures of amines, e.g. chrysoidine, NPhiN'CgH^NHg)^ to aniline and triamino-benzene, and also for reducing aromatic nitro- compounds to the corresponding hydroxylamines, e.g. C 6 H 6 N0 2 C 6 H 5 -NH*OH, a reaction which proceeds extremely readily in the presence of ammonic chloride solution. The same reagents are extremely useful in converting sulphonic chlorides into sulphinic acids, C 6 H 5 'S0 2 C1 * C 6 H 5 -S0 2 H. (v) Aluminium amalgam (Cohen and Ormandy, B. A. Eeport, 1889, 550) is also a useful neutral reducing agent in the presence of water; by this method nitro-derivatives are readily transformed into hydroxylamines, and ketones to secondary alcohols. B. Among other chemical methods we may mention heating with metals. Thus azo-benzene is formed when azoxy-benzene is heated with metallic iron, anthracene when alizarin is heated with zinc dust, and pyrrole when succinimide is heated with the same reagent. In all these cases the metal abstracts oxygen and is converted into an oxide. It is a method fre- quently adopted when dealing with unknown complex sub- stances and it is desired to know from what simpler compounds they are derived. Alcohol alone, as in the conversion of diazonium salts into hydrocarbons : H = C 6 H 6 + N 2 + HC1 + CH 3 .CHO (p. 387). Sodium ethoxide, or often alcoholic potash, for the reduction of nitro-compounds to azoxy- or azo-compounds (De Bruyn), and also for reduction of deoxy-benzoin and other aromatic ketones to secondary alcohols, e.g. hydroxy-dibenzyl : C 6 H 6 .CO-CH 2 .C 6 H 5 -> C 6 H 6 .CH(OH).CH 2 .C 6 H 6 (J. C. S. 1895, 604). Sodium stannite, obtained by adding an. excess of sodium hydroxide to stannous chloride, is employed for preparing azo-compounds from nitrated hydrocarbons, for the reduction of diazonium salts to hydrocarbons, e.g. benzene from benzene diazonium chloride. An interesting reduction is the conversion of jMiitro-benzyl chloride into dinitro-dibenzyl : 2N0 2 .C 6 H 4 .CH 2 C1 -> N0 2 .C 6 H 4 .CH 2 .CH 2 .C 6 H 4 .N0 2) as the nitro-groups are left intact. (B480) 2Q 610 XUV. REDUCTION Hydrogen sulphide, or more frequently ammonium sulphide, in alcoholic solution (Cohen and M'Candlish, J. C. S. 1905, 1257), is made use of for the reduction of nitro- and nitroso- derivatives to amines, and is especially useful when several nitro-groups are present and it is required to reduce only one, e.g. 0^H 4 (N(X) a -> m-N0 2 .C 6 H 4 .NH 2 , C 6 H 2 Me(N0 2 ) 3 _* NH 2 C 6 H 2 Me(N0 2 ) 2 , &c.; also 0-nitro-cinnamic acid * a- hydroxy-quinoline or carbostyril (p. 546). In many cases sulphur-derivatives are formed instead of simpler reduction products, especially with ketones or aldehydes. Sulphurous acid is used in reducing quinones to quinols, e.g. : C 6 H 4 2 + H 2 S0 3 + H 2 = C 6 H 4 (OH) 2 + H 2 S0 4 ; and sodium hyposulphite, Na 2 S 2 4 , is an extremely useful reagent for preparing leuco-compounds from dyes. C. Catalytic Reduction, or reduction by means of hydro- gen in presence of finely-divided metals. The catalytic action of finely-divided substances, especially platinum black, in the combination of sulphur dioxide and oxygen, or hydrogen and oxygen, or in the decomposition of hydrogen peroxide, is well known. In a similar manner, numerous carbon com- pounds, when mixed with excess of gaseous hydrogen and passed over a layer of platinum black at a moderate tem- perature, undergo complete reduction. The action of other metals in a fine state of division has been investigated in recent years (1897-1911) by Sabatier and Senderens. They find that nickel, cobalt, copper, and iron can act in somewhat the same manner as platinum black, and that of these nickel is the most efficient. It is necessary that the metal shall be in an extremely fine state of division, and this is accomplished by reducing the metallic oxide in a current of hydrogen at a temperature of about 300. The substance to be reduced is usually vaporized, mixed with excess of hydrogen, and passed over the metal heated to a temperature which varies somewhat with the different substances, but usually lies between 160 and 250. A few grams of the metal are usually sufficient, and it retains its activity for a long time. The finely -divided metal appears to transform the hydrogen into an active condition comparable with what is usually termed the nascent state. Of the numerous reductions which have been accomplished by this process, we may mention the following: Carbon ' monoxide at 200 and carbon dioxide at 300 are reduced to CATALYTIC REDUCTION 611 methane and water. Ethylene, propylene, /?-hexene, a-octene, &c., are quantitatively reduced to the corresponding paraffins. Acetylene at 150 and o-heptine at 170 yield ethane and heptane respectively. Aromatic hydrocarbons, e.g. benzene, toluene, xylene, cymene, at 180 yield their hexahydro-deriva- tives. Ethyl-benzene reacts in a somewhat curious manner; it appears to be first reduced to its hexahydro-derivative, CgHn'CgHg, but this is partially reduced to CJLj-CHg and CH 4 . Similarly phenyl- acetylene, C 6 H 5 C:CH, yields a mixture of ethyl - cyclohexane, methyl - cyclohexane, and methane. The terpenes limonene, sylvestrene, terpinene, menthene all yield ^-methyl-isopropyl-cyclohexane. Pinene yields a dihydro-derivative and naphthalene a tetrahydro- compound, and this with more hydrogen, dekahydro - naph- thalene, C 10 H 18 (Leroux). . Aliphatic nitriles at 180-200 yield primary amines, and finally secondary and tertiary amines and ammonia: E-ClSr -* K.CH 2 -NH 2 ; 2K-CH 2 .NH 2 * ( Aromatic nitriles yield ammonia and an aromatic hydro carbon : c 6 H 6 CN + 3H 2 = C 6 H 6 .CH 3 + NH 3 . Aromatic chloro-derivatives are readily dehalogenized at temperatures above 270 : C 6 H 6 C1 C 6 H 6 , and similarly for polychloro-derivatives. The presence of CHg, OH, and NH 2 groups appear to facilitate reduction : C1.C 6 H 4 .N0 2 C 6 H 6 .NH 2 ,HC1. Aliphatic nitro-compounds at 150- 180 yield the corre- sponding primary amines, but at higher temperatures paraffins and ammonia. Aromatic nitro-compounds are best reduced in presence of copper at 300-400; in this manner nitro- benzene yields aniline and a-nitro- naphthalene a-naphthyl- amine; whereas, when nickel is used, a-nitro -naphthalene yields ammonia and tetrahydro-naphthalene. Phenol, o-cresol, thymol, and carvacrol at 170- 180 are reduced to their hexahydro-derivatives, as are also methyl- and ethyl-anilines. Aniline at 190 also yields its hexahydro- derivative, cyclohexylamine, C-H n NH 2 , but at the same time dicyclohexylamine, (C 6 H n ) 2 NH, and cyclohexyl-aniline, are produced. 612 XLIV. REDUCTION At moderate temperatures (130-160) polyhydric phenols yield corresponding hexahydro-derivatives. Alcohols are formed by the reduction of aldehydes and ketones at temperatures slightly above their boiling-points, e.g.: (C 2 H 5 ) 2 CO -* (C 2 H 6 ) 2 CH.OH. Olefine derivatives are readily transformed into the corre- sponding saturated compounds at moderate temperatures, and compounds of the aromatic series, e.g. cinnamic acid, can be reduced to saturated compounds without the benzene nucleus being affected. Unsaturated ketones, e.g. mesityl oxide and phorone, can be reduced to the corresponding saturated ketones. Diketones yield various products: thus diacetyl at 140-150 yields a mixture of hydroxyketone and glycol; acetonylacetone yields the anhydride of the corresponding glycol; benzil, benzoin, and benzoylacetone yield the corre- sponding hydrocarbons. Lsevulic acid yields valerolactone, quinones yield quinols, and carbylamines, alkyl isocyanates, and oximes yield mixtures of amines, mainly secondary. (Sabatier and Senderens, Annales, 1905 [viii], 4, 319; Sabatier and Maihle, ibid. 1909, 16, 70; Sabatier, B. 1911, 44, 1984.) Recent experiments have shown that finely divided palla- dium or platinum can bring about the reduction of various carbon compounds at moderately low temperatures. Paal and Gerum (B. 1907, 40, 2209) show that when hydrogen is passed through an alcoholic solution of nitrobenzene mixed with a small amount of colloidal platinum, a 50-per-cent yield of aniline can be obtained at temperatures between 65 and 85. They also show (B. 1908, 41, 2273; 1909, 42, 1553, 2244, 3930) that unsaturated acids and esters, e.g. fumaric acid, maleic acid, cinnamic acid, and methyl cinnamate can be reduced to their saturated analogues by passing hydrogen into their alcoholic solutions at the ordinary temperature, provided small amounte of colloidal platinum or palladium, or even of palladium black, are present. They have used the method for converting unsaturated oils (oleic acid derivatives) into saturated glycerides. (Cf. also Willstatter and Mayer, ibid. 1475, 2199.) The most effective reagent appears to be colloidal palladium. On this reaction FoJcin (Abs. 1908, ii, 637) suggests a method for determining the " hydrogen value " of unsaturated acids by ascertaining the volume hydrogen absorbed by an alcoholic solution of a known weight of the CATALYTIC REDUCTION 613 unsaturated compound when well shaken with the gas in the presence of molecular platinum. A. Skita prepares the col- loidal palladium by the addition of gummi arabicum to a slightly acidified solution of palladous chloride, and shows that unsaturated ketones are converted into saturated, that citral yields citronellal and citronellol, and that many alka- loids take up hydrogen (B. 42, 1627; 44, 2862). The reduction proceeds most rapidly when the hydrogen is under an increased pressure of - 25 to 1 atmosphere. (Skita and Hitter, B. 1910, 43, 3393.) By this method un- saturated ketones are reduced to saturated without the carbonyl group being affected: d-pulegone * e-menthone, mesityl oxide methyl -isobutyl ketone. An exception is met with in phorone (p. 137), which yields di-isobutyl car- binol. If, however, a smaller pressure is used the reduction stops at the formation of the saturated ketone, valerone. Similarly in the other cases, if the pressure of the hydrogen is increased, a saturated secondary alcohol is obtained. Cyclic ketones and aromatic aldehydes can be reduced to alcohols, using a pressure of 5 atmospheres. Skita (B. 44, 2862, and Chem. Zeit., 1911, 35, 1098) shows that in many cases a solu- tion of palladous chloride in hydrochloric acid can be used, instead of the colloidal metal, with equally good results. Ipatie/(B. 34, 596, 3579; 35, 1047, 1057; 36, 1990, 2003, 2014, 2016; 37, 2961, 2986; 40, 1270, 1281, 1827; 41, 991, 993, 996, 1001; 42, 2089, 2092, 2097) has studied the re- duction by numerous carbon compounds with hydrogen under pressures of 100-120 atmospheres in the presence of various catalysers. A special iron or gun-metal bomb has been constructed for this purpose, and can be heated to the required temperature in an electric furnace. Of the catalytic agents investigated, namely, iron, nickel, copper, aluminium, nickelous and nickelic oxide (Ni 2 3 ), the last named was found to be the most effec- tive, and only 2-3 grm. were required for 20-30 grm, of the substance to be reduced. The oxide may be used a second time, but afterwards is less active; analysis of the recovered oxide indicates that only a comparatively small amount of reduction to metallic nickel has taken place. In most cases the best temperature is 230-260. Under such conditions, acetone yields pure isopropyl - alcohol ; phenol, hexahydro- phenol; diphenyl, dicyclohexyl ; naphthalene, tetra- or deka- hydronaphthalene; dibenzyl, dicyclohexylethane; a- and p- 614 XLIV. REDUCTION naphthols, o- and /2-dekahydronaphthols, and similarly for sodium /3-naphthioate; benzophenone, diphenylmethane; so- dium benzoate, sodium hexahydrobenzoate (60 per cent yield of pure acid); aniline, hexahydroaniline (50 per cent yield); diphenylamine, dicyclohexylamine (C 6 H n ) 2 NH; quinoline, de- kahydroquinoline; anthracene, perhydroanthracene, C 14 H 24 ; phenanthrene, perhydrophenanthrene, C 14 H 24 ; acenaphthene, dekahydroacenaphthene. In the last-mentioned reactions it is necessary to repeat the reduction three times in order to obtain the perhydro - derivatives. Olefines are reduced to paraffin derivatives. It is claimed that this method is much better and yields purer products than Sabatier and Seiiderens' method of reducing with hydrogen at atmospheric pressure and in the presence of finely divided nickel. D. Electrolytic Reduction. Within recent years, numerous reductions have been effected by electrolytic methods. The basis of all these methods is the fact that when an electric current is passed through an aqueous solution of an acid or an alkali, using metal electrodes, hydrogen in the nascent state is produced at the cathode or negative terminal. The actual products formed are dependent not merely on the substances reduced, but also upon the conditions, among the most important of which we may mention: (a) nature and concentration of solvent, e.g. dilute or concentrated acid, alkaline or neutral solvent; (b) strength of current or the current density, i.e. the intensity of the current per square decimetre of electrode; (c) the materials of which the elec- trodes are made, due to the difference of potential at which the hydrogen ions are discharged (as a rule platinum, mercury or lead electrodes are used); and (d) the temperature. The method has been mainly used for the reduction of aro- matic nitro-compounds, of ketones, and of unsaturated acids. In many cases the reduction is carried out in a double cell pro- vided with a diaphragm, (a) The cathode solution is placed in an ordinary unglazed porous cell, and this is introduced into a beaker which serves as the anode compartment; or (b) two glazed pots with small perforations are used, and the small an- nular space between these is packed with asbestos paper. If necessary the liquid can be agitated by using a rotating cathode. The reduction of nitro-benzene may be cited as one of the best examples which show the effect of conditions on the nature of the product: 4LECTROLYTIO REDUCTION 615 .^- 3 Current ensity in imperes. 2 2 II . I! s P O 03 p, S.s S o^ i|i p fto Cold satu sodic ca ate soluti porous ce 8.2 Jfi 40 "73 ncentrated hy drochloric acid 616 XLV. OXIDATION In the reduction of ketonic compounds, Tafel (B. 1900, 33, 2209) has shown that the best effects are obtained by using pure lead electrodes, as the hydrogen ions are thus discharged at a higher potential than when other metals are employed, and by employing in the cathode compartment 30-60 per cent sulphuric acid; with stronger acid, reduction of the acid occurs and sulphur is deposited. It is also essential that the current density shall be as low as possible. (For preparation of cells, see Tafel.) Acetone when reduced under such con- ditions, using mercury as cathode, yields isopropyl alcohol; but under similar conditions with a lead cathode it yields a mixture of isopropyl alcohol and pinacone. Camphor may be reduced to borneol (p. 568), and caffeine to deoxy-caffeine : NMe.CO NMe.CH 2 CO C-NMe\ CO C-NMex .C-N=/ &Me-C.N=/ Similarly uric acid may be reduced to purone : NH-CO NH-CH 2 CO C-NHv CO CH.NH NH C-NHv CO CH.NHx .C-NH/' NH.CH-NH/ Further, acetanilide, CgH 5 NH CO CH 8 , may be reduced to ethyl-aniline, C 6 H 5 NH'CH 2 CH 3 ; pyridine to piperidine, using lead cathodes; aconitic acid to tricarballylic acid and cinnamic to hydrocinnamic acid, by using mercury cathodes. The esters of oxalic, malonic, acetoacetic, benzoic, and phthalic acids, when reduced electrolytically, yield ethers, e.g.: Ethyl benzoate *- benzyl-ethyl ether. XLV. OXIDATION Oxidation includes not only those processes in which oxygen is added to a compound, e.g. conversion of an aldehyde, K CH : 0, into an acid, R CO OH, but also processes in which hydrogen is withdrawn from a compound, e.g. transformation of a primary alcohol, R.CH 2 -OH, into an aldehyde, K-CH:0. In certain cases both processes can occur, e.g. oxidation of aniline, C e H 6 NH 2 , to nitroso-benzene, C 6 H 6 NO. OXIDATION 617 Moat of the oxidizing agents employed are substances rich in oxygen, e.g. potassic dichromate or permanganate, nitric acid, chromic anhydride, peroxides, &c. During the oxi- dation, although the organic compound is oxidized, the Oxi- dizing substance is reduced, e.g. nitric acid gives up part of its oxygen to the substance to be oxidized, and itself becomes reduced to nitrous acid or to various oxides of nitrogen. Oxygen itself is sometimes made use of as an oxidizing agent, but usually in the presence of a catalyser, e.g. finely- divided metals such as platinum black or one of the enzymes known as oxydases. Processes of oxidation, like those of reduction, depend not merely upon the substances to be oxidized, but also on the oxidizing agent selected, and on such conditions as the acid, alkaline, or neutral nature of the solvent, temperature, and concentration. Examples of this have previously been cited among the aromatic hydrocarbons. Thus w-xylene is not acted upon by dilute nitric acid, but with chromic anhydride yields isophthalic acid. A very good example is aniline: 'Manganese dioxide and) . -, -,.,., sulphuric acid ) ** ammonia and little qumone ; Dichromate mixture qumone: Alkaline permanganate * azo-benzene and ammonia; Acidified permanganate * aniline black; Neutral permanganate * nitro-benzene and azo-benzene, Bleaching-powder nitro-benzene; .Hypochlorous acid * >-amino-phenol. Compounds of similar constitution are not always oxidized in the same manner; thus, to oxidize j9-nitro-toluene or p-nitTO- cinnamic acid the best reagent is dichromate mixture, but for the isomeric 0-compounds, dilute nitric acid or permanganate are recommended. The inhibiting influence of halogen and other negative radicals in the o-position with regard to the alkyl group, on the oxidation of such hydrocarbons by means of acid oxidizing agents, has already been referred to (p. 436), and also the fact that the final product of oxidation of a benzene homologue depends on the number and positions of the side chains, and not on their length, each yielding ulti- mately a C0 2 H group. When a compound like cymene, CH 3 C 6 H 4 C 3 H 7 , is selec tively oxidized, it is usually the longer side chain which is first affected; and it has been found possible, in a few cases, to carry the oxidation to a stage where a long side chain has 618 XLV. OXIDATION become only partially oxidized, e.g. aceto-mesitylene, CLH 2 Me 3 CO'CHg, to mesityl-glyoxylic acid, C 6 H 2 Me 3 -CO.C0 2 H; m- butyl toluene, CH 3 'C 6 H 4 .C 4 H 9 , by nitric acid at 180, to m- mejthyl-phenyl-propionic acid, CH 3 C 6 H 4 CH 2 CH 2 . C0 2 EL Cohen and Miller (J. C. S. 1904, 174, 1622) find that com- pounds containing chlorine or bromine in the meta-position with regard to a methyl group are least readily oxidized by nitric acid, those with similar substituents in the para-position most readily, and those with 0-chloro- and bromo-substituents are intermediate. In certain cases of oxidation, labile groups are present which have to be protected from the oxidizing agent; two such groups are the amino- and aid ehydo - groups. An amino- or imino-group can often be protected from under- going oxidation by transformation into the acetylated group NHAc or :NAc, or even better, into a nitroso-derivative, :N*NO. The further oxidation of an aldehydo- to a car- boxylic group can often be prevented by the addition of some substance to the oxidizing mixture which will yield a spar- ingly soluble compound with the aldehyde; such compounds are a primary aryl-amine, which forms a compound of the type of benzylidene-aniline, C 6 H 6 CH : NC 6 H 5 , sodic hydric sulphite, or calcium naphthionate, the calcium salt of 1-amino- naphthalene-4-sulphonic acid. From the additive compound to which the last salt gives rise, the aldehyde may be ob- tained by distillation in steam. A. Potassium Permanganate, This is the commonest and one of the most useful oxidizing agents, as it may be used in 'neutral, alkaline, or acid solution. Other permanganates are also employed, e.g. the calcium and barium salts, especially for the oxidation of complex proteins. (a) Alkaline Solution. Even when no alkali is added at the beginning, the solution becomes alkaline during the reaction. The permanganate, a derivative of Mn 2 r , becomes reduced to hydrated Mn0 2 , and thus each molecule of permanganate, K 2 Mn 2 8 , can yield three atoms of nascent oxygen: K 2 Mn 2 O 8 4-H 2 O = 2MnO 2 -f 2KOH + 3O. When the product formed is an acid, this remains dissolved in the alkaline liquid, and may often be obtained by the addition of mineral acid after the manganese dioxide has been removed by filtration. In this manner, numerous ben zene hydrocarbons and their derivatives can be oxidized to OXIDATION WITH PERMANGANATE 619 the corresponding acids, e.g. ^3-chloro- toluene to j9-chloro- benzoic acid, naphthalene to phthalonic acid, 0-C0 2 HC 6 H 4 COC0 2 H. Other examples are the conversion of o-nitro- Slienol into dinitro - dihydroxy - diphenyl, N0 2 (OH)C 6 H 3 6 H 3 (OH).N0 2 , and of uric acid into allantoin (p. 294). The oxidation of olefine derivatives by two per cent perman- ganate (Fittig) is of extreme interest. Two hydroxyl groups are invariably added, and a glycol derivative formed; thus cinnamic acid, C 6 H, CH : CH C0 2 H, yields phenyl-gly eerie acid, C 6 H 5 .CH(OH).CH(OH).C0 2 H. When a stronger per- manganate solution or a more powerful oxidizing agent is used, the unsaturated compound is ruptured at the point of the double bond, and a mixture of less complex acids or ketones formed. An excess of alkali is often added to the permanganate before use. Under these conditions 0-toluic acid yields phthalic acid, and the method is largely made use of for oxidizing 0-sub- stituted derivatives of toluene, &c. When the solution is dilute and the temperature is kept at 0, the oxidation is mild, and can stop at the formation of a glyoxylic acid, e.g. : C 6 H 2 Me 3 .(X).CH 3 C 6 H 2 Me 3 .CO.CO 2 H; otherwise a substituted benzoic acid in this case C 6 H 2 Me 3 C0 2 H is always formed. Substituted cinnamic acids, by this method, can be converted into corresponding benzoic acids, e.g. : N0 2 (OH)C 6 H 3 .CH:CH.C0 2 H to N0 2 (OH)C 6 H 3 .CO 2 H. Similarly, hydrocarbons of the type of triphenyl-methane, CHPhg, can be oxidized to carbinols, e.g. CPh 3 -OH, and compounds of the type of diphenyl-methane, CH 2 Ph 2 , to ketones, CPh 2 -CO. (b) Neutral Solution, In a few cases it is necessary tc keep the solution neutral from beginning to end, and this is accomplished by the addition of an excess of magnesic sul- phate, which yields insoluble magnesic hydroxide with the caustic potash produced during the oxidation. When acet-o- toluidide, CH 3 C 6 H 4 NH CO - CH 3 , is thus oxidized, an 80-per-cent yield of acetanthranilic acid, C0 2 H C 6 H 4 NH CO'CH 3 , is formed, whereas in the presence of alkali the yield is only some 30 per cent. (c) Acid Solution. Acetic or sulphuric acid is used, and the acid is added gradually with the permanganate. The 620 XLV. OXIDATION method is of use for the preparation of very stable compounds only, as the majority are completely decomposed by these reagents. The reaction is quite different from that in alka- line solution, the permanganate (a derivative of Mn 2 r ) is reduced to a manganous salt (derived from MnO), and thus each molecule of permanganate gives rise to five atoms of available oxygen: K 2 Mn 2 O 8 + 3H 2 S0 4 = 2MnS0 4 + K 2 SO 4 + 3H 2 O -f 5O. Sulphides or hydrosulphides in both the aliphatic and aro- matic series may be oxidized to sulphonic acids, a reaction which is useful for the preparation of certain naphthalene- sulphonic acids which cannot be obtained by direct sulphona- tion. o-Iodo-benzoic acid may be oxidized to o-iodoso-benzoic acid, tetrabromo-p-xylene to tetrabromo-terephthalic acid, and primary alcohols to aldehydes. B. Chromic Acid Derivatives, Chromic anhydride, Cr0 3 , is often used as an oxidizing agent when dissolved in glacial acetic acid, two molecules of the anhydride yielding three atoms of oxygen, 2 Cr0 3 = Cr 2 3 + 30. Usually only the theoretical amount required for the oxidation is used, and this is gradually run in from a dropping funnel. Quinoline homologues are oxidized to quinoline carboxylic acids, and aromatic alcohols to aldehydes, if a primary amine is present to form a Scki/'s base (p. 425). Even benzene homologues may be oxidized to aldehydes in the presence of acetic anhydride, as the acetyl derivatives thus formed are stable. Chromyl chloride, Cr0 2 Cl 2 , the chloride of chromic acid, is used for oxidizing benzene hydrocarbons to aldehydes (Etard's reaction, p. 424). The usual method is to dissolve the hydro- carbon and chromyl chloride separately in carbon disulphide, and to run in the chloride solution until the red colour per- sists, and then to decompose with water. A precipitate of a double compound, e.g. C 6 H 5 CH 3 , 2Cr0 2 Cl 9 , is first produced, and this is decomposed by water according to the equation : 3[C 6 H 6 CH 3 ,2Cr0 2 Cl 2 ] = 3C C H 6 CHO -f 4OCl 3 -f 2H 2 CrO 4 + H 2 O. The usual method of using chromic acid is in the form of a mixture of a dichroinate and sulphuric acid, which react according to the equation: K 2 2 7 + 4H 2 S0 4 = K 2 S0 4 -f Cr 2 (SO 4 ) 3 -f 4H 2 O + 3O, each molecule of dichromate yielding three atoms of available OXIDATION WITH NITRIC ACID 621 oxygen. Sometimes potassic dichromate is used, but more frequently the sodic salt, as it is cheaper and more readily soluble in water. As a rule, the dichromate mixture is added gradually to the oxidizable substance. It is the common method of preparing aldehydes from alcohols (see Acetalde- hyde, p. 128), and also from aromatic hydrocarbons, as there is not the same tendency for the -CHO group to be further oxidized as when permanganate is employed. Complex alco- hols may also be oxidized to ketones or aldehydes, e.g. menthol to menthone (p. 578). Many compounds, such as hydroxy- acids, ketones, ketonic acids, &c., are ruptured by chromic acid mixture, and acids or ketones containing a smaller number of carbon atoms are formed. This is the oxidizing agent usually employed for the pre- paration of quinones, e.g. from aniline, and as a rule the tem- perature should be kept at about 0. According to Bamberger, the following series of reactions occur: 6 H 6 .NH 2 -* C 6 H 6 .NH.OH -> p-OH.C c H 4 .NH 2 O:C 6 H 4 :O. C. Nitric Acid. Examples of the complete oxidizing action of fuming nitric acid are met with in the ordinary Carius method for estimating halogens or sulphur. One of the chief drawbacks of nitric acid is, that in addition to being an oxi- dizing agent, it is also a nitrating agent, and the products of oxidation, even when dilute acid is used, contain smaller or larger amounts of nitro- derivatives. By means of dilute nitric acid many benzene homologues are oxidized to car- boxy lie acids, but the process is slow; thus pentamethyl benzene dissolved in benzene requires sixty hours' boiling to oxidize it to tetramethyl-benzoic acid, and slightly longer time is required to oxidize 2 : 6-chloro-nitro-toluene to the corresponding acid. An interesting oxidation is that of m-butyl-toluene to w-methyl-phenyl-propionic acid, and a somewhat complex oxidation is that of camphor to cam- phoronic acid (p. 586). Kmffl (R 1889, 21, 2735) introduced the use of concentrated nitric acid (sp. gr. 1-5) for oxidizing purposes. The admixture was effected at 0-10, the tem- perature gradually raised to 50, and the product poured into water. This is a very good method for oxidizing compounds which are already nitrated, as in other cases nitro-derivatives are very liable to be formed. Dinitroxylene is oxidized in this way to dinitrophthalic acid. Sulphoxides, e.g. Et 2 SO, may be oxidized to sulphones, EtgSO^ iodo-benzoic acid to 622 XLV. OXIDATION iodoso-benzoic acid, cane-sugar to oxalic acid, &c. The method adopted in oxidizing glycerol to glyceric acid is to allow the aqueous solution of the glycerol to float on concen- trated nitric acid. A mixture of concentrated nitric and sulphuric acids, which is an extremely good nitrating agent, may be used for oxidiz- ing purposes, e.g. 0-nitro-benzyl alcohol to the corresponding aldehyde, of ^-nitro-cinnamic acid to ^-nitro-benzaldehyde, and of 5-trinitro-toluene to s-trinitro-benzoic acid. D. Sulphuric Acid. One of the oldest examples of the oxidizing action of concentrated sulphuric acid is the con- version of ethyl mercaptan, C 2 H 6 SH, to ethyl disulphide, (C 2 H 5 ) 2 S 2 , and another that of piperidine to pyridine. Schmidt introduced the use of fuming sulphuric acid (60 or 70 per cent S0 3 ) at low temperatures for converting alizarin and other hydroxy- derivatives of anthraquinone into tri- to hexahy- droxy-derivatives, many of which are important dyes. The hydroxy-groups form an ester with the sulphuric acid, but this is readily hydrolysed when boiled with dilute acid. Concen- trated sulphuric acid may also be used for the preparation of the same compounds, and the yields are largely increased by the addition of boric acid, this being probably due to the fact that boric esters are formed, which prevent the removal of the hydroxy-groups when once introduced. An oxidizing action of commercial importance is the con- version of naphthalene into phthalic acid by means of con- centrated sulphuric acid and a small amount of mercuric sulphate at a temperature above 300. E. Peroxides. The peroxides mainly employed are Mri0 2 , Pb0 2 , and occasionally H 2 ? . Lead peroxide is frequently used in the form of a paste with acetic acid, one of the earliest oxidations with this reagent being that of uric acid to allan- toin (p. 294). Characteristic oxidations are (i) that of a- hydroxy-acids to aldehydo-acids, with one less carbon atom (p. 305), e.g.: C0 2 H.CH(OH).CH 2 .CO 2 H -* CO 2 + 0:CH.CH 2 .CO 2 H; (ii) of alkyl acetates to aldehydes, e.g. : o-N0 2 .C 6 H 4 .CH 2 .O.CO.CH 3 to o-N0 2 .C 6 H 4 .CH:O; (iii) of triphenyl-methane-derivatives to the corresponding carbinols, the salts of which are dyes, e.g.: OXIDATION WITH PEROXIDES 623 and (iv) of amino-hydroxy-derivatives of anthraquinone to the corresponding polyhydroxy-derivatives, the NH 2 being replaced by OH, a reaction which does not occur when the amino-group is acetylated. Manganese dioxide alone, or in the presence of sulphuric acid, may be used for converting CH 3 groups in benzene homologues into aldehydo-groups. The mixture is kept stirred, and an excess of hydrocarbon is always present. Benzaldehyde, o-chloro-benzaldehyde, j?-nitro-benzaldehyde, terephthalic aldehyde, &c., have been prepared by this method. A remarkable oxidation is that of benzene to benzoic acid by means of the peroxide and sulphuric acid. Hydroxy-acids are often ruptured by these reagents, e.g. lactic acid, CH 3 - CH(OH)-C0 2 H, yields aldehyde and carbonic acid. This is the basis of a method for estimating the strength of solutions of lactic acid by determining the amount of aldehyde formed. The same reagents are also used for the oxidation of alkaloids, and for the conversion of the leuco-bases of triphenyl-methane dyes into the dye salts, e.g. jp-leucaniline into ^-rosaniline. Hydrogen peroxide is often used in the presence of potassium hydroxide for the preparation of organic peroxides, e.g. diethyl- peroxide, Et 2 2 , benzoyl-peroxide, (C 6 H 5 CO) 2 2 . Piperidine, when oxidized with three per cent peroxide solution, yields glutaric acid owing to the rupture of the ring. Benzene, with the peroxide, yields a certain amount of phenol. Azo-com- pounds are converted into corresponding azoxy-derivatives, and phenols into dihydric phenols or quinones. Fatty acids are converted into ketones, E-CHg-CO-OH KCH 2 . CO- CKLE, (DaMn, Am. C. J. 1910, 44, 41). Fenton and others (J. C. S. 1894, 899; 1895, 48, 774; 1899, 1) have made use of hydrogen peroxide in the presence of small amounts of ferrous salts; by this method the following reactions have been effected: Glycollic acid, OH-CH 2 .CO S H, > glyoxylic acid, CHO-C0 2 H; Lactic acid, CH 3 .CH(OH).C0 2 H, pyruvic acid, CH 8 .CO-C0 2 H; Tartronic acid, OH CH(C0 2 H) 2 , -* mesoxalic acid, CO(C0 2 H) 2 ; Gly eerie acid, \ fhydroxy-ruvic acid H OH.CH 2 .CH(OH).C0 2 H,j ' ' \ Tartario acid, _^ 1 , /dUiydroxy^maleic : acid, CO a H.CH(OH).CH(OH).C0 2 H,/ ' * I CO a H.C(OH):C(OH).C0 2 H; Polyhydric alcohols, * aldoses. F. Oxygen itself can often be used for oxidation, generally in the presence of platinum black or platinized asbestos. Denn- stedt's method for estimating carbon and hydrogen in organic 624 XLV. OXIDATION compounds is based on this. Many aldehydes, when exposed to moist air, are transformed into acids; thus specimens of benzaldehyde which have been kept for some time contain appreciable amounts of benzoic acid. Cinnamic alcohol may be oxidized to cirmam aldehyde, glycerol to glyceraldehyde, and methyl alcohol to formaldehyde in presence of slightly oxidized copper. Alkaline solutions of polyhydroxylic phenols are readily oxidized (see Pyrogallol), and a similar solution of gallic acid yields the yellow dye galloflavin. Glock has shown that methane and air, when repeatedly passed over heated metallic copper at 600, yield methyl alcohol and formalde- hyde, and that ethane and air yield ethyl alcohol, acetalde- hyde, and acetic acid. [Compare also Bone's experiments (pp. 36 and 37).] Ozone may also be used as an oxidizing agent; it is employed commercially for refining oils, &c. (cf. J. Ind. 1898, 1101). G. Harries (A. 1905, 343, 311; 1910, 374, 288) has examined the action of ozone on various types of carbon compounds, mainly in glacial acetic acid solution. Methane, ethyl alcohol, &c., are oxidized to aldehydes and acids, hydro- gen peroxide also being formed. Saturated aldehydes and, to a certain extent, ketones yield labile peroxides of the type, R CH : : 0. Most unsaturated hydrocarbons and alcohols combine with ozone, yielding ozonides, e.g. C 2 H 4 -J-0 3 , ethylene ozonide. The structure of such compounds is usually repre- sented as follows, e.g.: CH 2 and for each ethylene linking one molecule of ozone is added. Many compounds combine with more than this amount of ozone, yielding oxozonides, e.g. propylene yields a product, C 3 H 6 -}-0 4 , which are not readily transformed into normal ozonides. They are regarded as derived from the hypothetical 4 . Unsaturated carbonyl derivatives, e.g. acids, aldehydes, and ketones, also combine with ozone, yielding ozonides; they can, however, combine with a fourth atom of oxygen, yielding perozonides, which are decomposed by water, yielding the ozonide and hydrogen peroxide. The three atoms of the ozonide are regarded as attached to the two carbon atoms of the ethylene linking, whilst the fourth atom is attached to the carbonyl group. Oleic acid perozonide is represented Mi OXIDATION WITH OZONE 625 CH 3 .[CH 2 ] r .CH . C O-O-O OH The ozonides are decomposed when gently heated, or when the solutions in glacial acetic acid are warmed. Oleic acid ozonide decomposes into the four products: CH 3 .[CH 2 ] 7 .CH:0 + I. Nonaldehyde. QS IL and C III. Nonaldehyde N U IV. Azelaic acid semi- peroxide. aldehyde. Some of these products are readily oxidized, e.g. nonalde- hyde yields the corresponding acid, and the semialdehyde yields azelaic. At the same time the aldehyde peroxides are transformed into the isomeric carboxylic acids, so that appreci- able amounts of nonylic and azelaic acids are always found in the final decomposition products. The nonaldehyde peroxide formed in this way is isomeric, and not identical with the per- oxide obtained by the direct action of ozone on the aldehyde. It is more stable, has m.-pt. 73, and is represented by for- mula III. Such decompositions of ozonides can be used for determin- ing the position of the ethylene linking in the molecule of the original compound, and also for the preparation of certain aldehydes, aldehydic acids, and dialdehydes. Benzene yields a highly explosive triozonide, (LHgOg. G. Other Oxidizing Agents. Chlorine and bromine are generally used in alkaline solution, i.e. in the form of hypo- chlorite or hypobromite. As examples, we have the well- known Hofmann reaction, the conversion of amides, and imides such as succimmide and phthalimide, into amines or nitriles (pp. 183 and 184); also the oxidation of reduced benzene derivatives back to the original benzene compound. An in- teresting oxidation is that of benzylidene-acetone to cinnamic acid with four per cent sodium hypobromite : C 6 H 6 . CH : CH - CO CH 3 -f 3 NaBrO and of potassium cyanide to cyanate by hypochlorite. Bromine water itself is frequently used for the oxidation of sugars, e.g. (8480) 8& 626 XLV. OXIDATION of an aldose to the corresponding monobasic acid; thus gly- cerose to gly eerie acid, glucose to gluconic acid. Less common oxidizing agents are potassic ferricyanide, which is reduced to the f errocyanide : 2K 3 FeC 6 N 6 + 2KOH = 2K 4 FeC 6 N 6 + H 2 O + 0. s-Trinitro-benzene may be oxidized by this reagent to picric acid, phenyl-acetylene to diphenyl-diacetylene, CPh:CC:CPh, nitroso- to nitro- derivatives, quinone-dioxime to dinitroso- benzene, benzene-diazo-oxides to salts of benzene-diazoic acid, C 6 H 5 N : NO OH, and nitro-toluenes to nitro-benzoic acids. Ferric chloride: 2FeCl 3 + H 2 = 2FeCl 2 + 2HCl + 0, may be used for oxidizing hydroxylamine derivatives to nitroso-compounds, e.g. : C 6 H 4 Br.NH.OH - C 6 H 4 Br.NO; quinols to quinones, and naphthols to dinaphthols: OH.C 10 H 6 .C 10 H 6 .OH. Silver oxide oxidizes glycerol to glycollic acid, and gener- ally aldehydes to acids, and 0-dihydroxy-benzene to 0-benzo- quinone. Mercuric oxide, usually with alkali, e.g. barium hydroxide, is used for oxidizing fructose to trihydroxy-butyric acid and glycollic acid, and glucose to gluconic acid. It also oxidizes unsym. diethyl - hydrazine to tetraethyl - tetrazone, NEt 2 N : N NEt 2 , and sym. diethyl -hydrazine to mercury- diethyl, nitrogen, and water. Nitre-benzene is used as an oxidizing agent in the manufacture of magenta (p. 487), and also in the Skraup synthesis of quinoline (p. 542). Potassium persulphate, mixed with concentrated sulphuric acid, is known as Caro's reagent or sulphomono-per-acid, and can oxidize sali- cylic acid to 2:5-dihydroxy-benzoic acid. It is also used for oxidizing various terpene derivatives, and readily oxidizes aro- matic primary amines to nitroso-derivatives, e.g. : C fl H 5 NH 2 C 6 H 6 NO. H. Electrolytic Oxidation. Organic compounds may be oxidized by means of the oxygen formed at the anode of an electrolytic cell. The method is not so general in application as electrolytic reduction, as it is extremely difficult to stop the reaction at the right point. Even when the theoretical ELECTROLYTIC OXIDATION 627 amount of oxygen has been formed, it is often found that part of the compound is unacted on, and part has been com- pletely oxidized. The following are fairly typical examples : Purpuro-gallin is formed by the electrolysis of a solution of pyrogallol in sodium sulphate solution, using a rotating platinum anode of 2 sq. dm. The reaction is complete after 6-8 hours with a C.D. of 1-5-2 amperes and an E.M.F. of 4-3-4-5 volts. Anthraquinone may be prepared by oxidizing an emulsion of anthracene, water, and sulphuric acid, using a rotating lead cathode, and a leaden vessel as anode. The best yields are obtained when an oxygen carrier, e.g. manganese sulphate, is employed with a temperature of 75-90, a C.D. of 1-2 am- peres, and an E.M.F. of 2'8-3'5 volts. Numerous azo-dyes have been obtained electrolytically; thus, Orange II, or fi - naphthol - azo benzene - sulphonic acid, OH.S0 2 .e 6 H 4 .N:N.C 10 H fl .OH (p. 502), is produced from an aqueous solution containing sodic sulphanilate, /3-naphthol, and sodic nitrite. The cathodes of nickel or platinum wire are placed in two separate cathodic compartments consisting of small porous cells and containing sodic hydroxide solution. The rotating anode is of platinum; and a C.D. of 8-12 am- peres, an E.M.F. of 15-18 volts, and as low a temperature as possible, give the best results. The homologues of benzene, when oxidized with platinum electrodes in the presence of sulphuric acid and acetone, yield aldehydes, e.g. toluene * benzaldehyde, o-xylene * o-toluic aldehyde, but the yields, as a rule, are not good. Ortho-substituents of a negative char- acter tend to inhibit such oxidations. Acetic acid solutions of p- and o-nitro-toluenes yield the corresponding nitro-benzyl alcohols, whereas the m-compound yields m-nitro-benzaldehyde. Benzyl sulphide yiolds benzylsulphoxide, benzyldisulphoxide, or tribenzylsulphonium sulphate according to conditions. XLVI. STEREO-CHEMISTRY OF SULPHUR, SELENION, TIN, AND NITROGEN COMPOUNDS Attention has already (pp. 154 and 213) been drawn to the fact that a compound containing an asymmetric carbon atom, Ca, b, c, d, exists in two optically active isomerides which can unite to form a racemic compound. The researches of Pope and others within the past few years have proved that compounds containing other quadravalent atoms, such as 628 XLVI. STEREO-CHEMISTRY OF SULPHUR, ETC. S, Se, and Sn, attached to four different univalent radicals, also exist in optically active isomeric forms. A. Sulphur Compounds (Pope and Peachey, J. C. S. 1900, 1072). The sulphur compounds selected were derivatives of methylethylthetine bromide: a product which can be prepared by the addition of bromo- acetic acid to methylethyl sulphide. The bromide was mixed with the theoretical amount of silver d-camphor-sulphonate in aqueous solution, the silver bromide removed, the filtrate evap- orated at 40, and the solid residue crystallized some 40-50 times from a mixture of absolute alcohol and dry ether. The sparingly soluble ^-methylethylthetine d-camphor-sulphonate, CHCH CO melts at 118-120, and has a molecular rotation [M] D * = + 68. The rotation for the camphor - sulphonate ion is 4-51-7, and this gives a rotation of +16-3 for the thetine ion. A very similar value has been obtained by repeatedly crystallizing the d- bromo- camphor -sulphonate. The corre- sponding platinichloride, (SMeEtCl-CH 2 .C0 2 H) 2 , PtCl 4 , has a molecular rotation + 30'2. Smiles (J. C. S. 1900, 1174) has obtained methylethyl- phenacylsulphine bromide: (from methylethyl sulphide and bromo-acetophenone) in opti- cally active modifications by a similar process. B. Selenion Compounds have been resolved by Pope and Neville (J. C. S. 1902, 1552). The compound used was methylethylselenetine bromide, SeMeEtBr CH 2 C0 2 H, ob- tained from methylethyl selenide and bromo-acetic acid; the corresponding d- bromo -camphor- sulphonate was repeatedly crystallized from alcohol, and the least soluble fraction melted at 168, and had [M] D = +330-8, which gives a rotation of + 60-8 for the methylethylselenetine ion. The corresponding salt of the /-base -f d-acid was isolated; it melted at 151, and had [M] D = +209 '6, which gives a value of 60 '4 for the Z-selenetine ion. The platinichloride * For meaning of this, see p. 627. OPTICALLY ACTIVE TIN COMPOUNDS 629 had a molecular rotation +55, but the mercuri - iodide, SeMeEtI.CH 2 .C0 2 H, HgI 2 , was optically inactive. C. Tin Compounds (Pope and Peachey, P. 1900, 42, and 116). A compound containing an asymmetric tin atom was prepared by the following series of reactions: 2SnMe 3 I + ZnEt 2 = 2SnMe 3 Et + ZnI 2 ; SnMegEt + 12 = SnMe 2 EtI + Mel; 2SnMe 2 EtI + ZnPr 2 = 2SnMe 2 EtPr + ZnI 2 ; SnMe 2 EtPr + I 2 = SnMeEtPrI + Mel. The methylethylpropyl-tin iodide (a liquid boiling at 270) was converted into the ^-camphor -sulphonate by means of silver d- camphor -sulphonate, and after the removal of the silver iodide the solution was evaporated, when crystals of d-methylethyl-7i-propyl-tin ^-camphor-sulphonate, SnMeEtPr- O S0 2 C 1? H 15 0, melting at 125-126, were obtained. In aqueous solution, [M] D = +95, which gives a value for the univalent ion, SnMeEtPr, of about -f 45. When the mother liquor from the above-mentioned crystals is evaporated, a further quantity of the same compound is obtained, and the operation can be continued until all the water has been expelled. No trace of /-methylethylpropyl-tin d-camphor- sulphonate can be isolated. Pope and Peachey attribute this to the conversion of the /-base into the d-base by continued racemization (p. 257), in the following manner: The solution of the racemic base with the d-acid deposits a portion of its d-base as the sparingly soluble salt d-base + d-acid; the excess of I- over d-base remaining in the solution racemizes as eva- poration proceeds, a further quantity of J-base separates as salt, and racemization of the residue again proceeds. A d-methylethyl-w-propyl-tin iodide with [a] D + 23 in ethereal solution has been prepared from the camphor- sulphonate. The resolution of tin compounds has also been accomplished by means of the d-bromo-camphor-sulphonate. If the aqueous solution of rf-methylethyl-n-propyl-tin d-bromo-camphor-sul- phonate is heated at 100 in a sealed tube for two hours, racemization proceeds, and the rotation [M] D -f 272 is that due to bromo-camphor-sulphonate ion only. D. Silicon Compounds. Silicon is the element most closely allied to carbon, and hence numerous attempts have been made to prepare optically active silicon compounds containing an asymmetric silicon atom. 630 XLVI. STEREO-CHEMISTRY OF SULPHUR, Eta It is only recently, however, that these experiments have met with success. Kipping (J. C. S. 1907, 91, 209) has pre- pared the compound ethylpropylbenzylphenylsilicane, by the following series of re- actions : SiCl 4 + MgEtBr = SiEtCl 3 + MgClBr SiEtCL -f- MgPhBr = SiEtPhCl 2 + MgClBr SiEtPhCL + MgPrBr = SiEtPhPrCl -f MgClBr SiEtPhPrCl -f MgBzCl = SiEtPhPrBz -f MgCl 2 . This hydrocarbon when sulphonated gives rise to benzene and a sulphonic acid: S0 3 H C 6 H 4 CH 2 SiEtPr SiEtPr CH 2 C H 4 S0 3 H, sulphobenzylethylpropylsilicyl oxide. As the formula indi- cates, this compound contains two similar asymmetric silicon atoms, and should presumably exist in the same number of isomeric modifications as tartaric acid (p. 249). One of the acids isolated by Kipping has been shown to be a ^-/-compound, and its salt with the active base, d-methylhydrindamine can be resolved into its optically active components when re- peatedly crystallized from acetone or aqueous methyl alcohol. The two acids have extremely low rotatory powers, e.g. [a] D 3 to 4. Similar active compounds containing an isobutyl in place of the propyl group have been obtained; they have [a] D 10'5. And still more recently compounds containing a single asymmetric silicon atom have been isolated, e.g. ethylpropyldibenzylsilicanemonosulphonic acid, CH 2 Ph SiEtPr CH 2 C fl H 4 S0 3 H, which can be resolved into active components by means of brucine. Most of the active silicon derivatives are character- ized by the close similarity between the active and racemic forms and by the low rotatory powers, so that it is difficult to say, in certain cases, whether resolution has been effected or not. Pope and PeacJiey conclude that all the elements of Group IV of the Periodic Classification, namely C, Si, Ti, Ge, Zr, Sn, Ce, Pb, Th, also probably O, S, Se, Te, should in a similar manner give rise to optical activity in their asymmetric derivatives. OPTICALLY ACTIVE NITROGEN COMPOUNDS 631 E. Nitrogen Compounds (H. 0. Jones, B. A. Eep. 1904, 169). (i) Terwlent Nitrogen Compounds. No optical activity has been met with in compounds of the type N a, b, c, and all attempts to resolve such compounds have proved fruitless. Jones and Millington (C. C. 1904, 2, 952) have attempted to resolve benzyl -phenyl-hydrazine by means of d- camphor -sulphonic acid, and to resolve methylethylaniline - sulphonic acid by means of brucine. Other chemists (Krafft, Behrend and Konig, Ladenburg) have attempted to resolve benzyl - ethyl - amine, p-tolyl-hydrazine, /?-benzyl-hydroxylamine, methyl-aniline, and tetra-hydroquinoline by means of d-tartaric acid. Kipping and Salway (J. 0. S. 1904, 438) have adopted the method of treating a secondary amine with a racemic acid chloride, namely 2-/-benzylmethylacetyl chloride, CHMeB 2 ^ COC1, and examining the substituted acid amide formed. With a true d-/-base, the following compounds should be formed: dBdA, IB I A, dElA, ZBdA, of which 1 and 2 form an enantiomorphously related pair, and 3 and 4 a similar pair. Thus the complete product would be a mixture of two racemic substituted acid amides. Experiments conducted with methyl- aniline, ^?-toluidine, phenyl-hydrazine, and benzyl-aniline gave a homogeneous product in each case. Similarly, when p-toluidine and benzyl-aniline are condensed with d-methyl- benzylacetyl chloride, no indication of the formation of iso- merides is met with. A pair of compounds, C 6 H 3 Me 2 NH . CHMe - CH 2 CHO, containing tervalent nitrogen and stated to be stereoisomeric, have been shown by Jones and White (J. C. S. 1910, 632) to be structurally isomeric. The general conclusion to be drawn is, that the centres of gravity ]of the three radicals, and also of the nitrogen atom itself, lie in a single plane, and the whole arrangement is the most symmetrically possible one. (Cf. Oximes, pp. 138, 429.) (ii) Quinquevalent Nitrogen Compounds. (For formation, see pp. 105, 379.) The most interesting type of compound is that in which all five radicals are different, e.g. N a, b, c, d, X. These compounds are quaternary ammonium salts, in which four of the radicals are alkyl groups, and the fifth an acid group. No cases of inactive isomerides have been met with. An example described by JFedekind, viz. methylallylphenyl- benzylammonium iodide, has recently been shown by H. 0. Jones (J. C. S. 1905, 1721) to be non-existent. The only known examples of stereoisomerides are the 632 XLVI. STEREO-CHEMISTRY 01* SULPHUR, ETC. optically active modifications in which compounds of the type methylethylpropylisobutylammonium chloride, N(CH 3 ) (C 2 H 5 )(C 3 H 7 )(C 4 H 9 )C1, exist. This type of compound is always obtained in an inactive form when synthesised in the laboratory by the addition of an alkyl haloid to a tertiary amine. In 1891 Le Bel claimed to have obtained a Icevo-modi- fication by means of penicillium glaucum (green mould), and in 1899 he confirmed this result. In the same year Pope and Peachey (J. C. S. 1899, 1127) obtained a resolution of Wede- Jcind's benzylphenylallylmethylammonium iodide by the aid of silver d-camphor-sulphonate. When the mixture of benzylphenylallylmethylammonium d-camphor-sulphonates is crystallized from acetone, a sparingly soluble fraction is obtained, and this, when treated with potassium iodide, yields an optically active iodide, N(C 7 H 7 ) (C 6 H 5 )(C 3 H 5 )(CH 3 )I, with [M] D + 192. H. 0. Jones (J. C. S. 1903, 1418; 1904, 223) has resolved phenylbenzylmethylethylammonium iodide and phenylmethyl- ethylallylammonium iodide by means of silver d-bromo-camphor- sulphonate. Jones has observed that many of these salts show a tendency to undergo racemization, and during the fractional crystallization of the salts it is advisable to keep the tempera- ture as low as possible. Auto-racemization (p. 257) occurs when the cold chloroform solutions are kept in the dark, a phenomenon also observed by Pope and Harvey (J. C. S. 1901, 828) with other optically active ammonium salts, and probably due to a partial dissociation of the quaternary ammonium salt into tertiary amine and alkyl iodide and subsequent recombina- tion. (For other optically active ammonium salts, see Wedekind, B. 1905, 38, 1838; Thomas and Jones, J. C. S. 1906, 280.) Quinquevalent nitrogen derivatives of the type Na 2 bcX, e.g. phenylallyldimethylammonium iodide, phenyldipropyl- methylammonium iodide, &c., do not exist in isomeric modi- fications, and attempts to resolve such compounds into optically active components have given negative results (J. C. S. 1897, 522; 1903, 1141, 1406; 1904, 412). Aschan (Zeit. phys. 1903, 46, 304) has prepared isomeric cyclic nitrogen compounds containing two quinquevalent nitrogen atoms, viz.: Br Br The one compound is formed by the union of ethylene-di- OPTICALLY ACTIVE NITROGEN COMPOUNDS 633 peridide with trimethylene bromide, and the other by the combination of trimethylene-diperidide with ethylene bromide. This isomerism can be accounted for if the bromine atoms and the central ring lie in one plane and the other rings in a plane at right angles to the first. A similar compound containing one nitrogen atom, has been shown by Scholz (B. 43, 2121) to exist in two opti- cally active forms. Methylethylaniline oxide, NMeEtO, has been resolved into active modifications by means of bromocamphorsulphonic acid. The base itself, probably NMeE^OH)^ has [a] D -25. The compound I NMeEtPh - CJJ 2 CH 2 CH 2 . NMeEtPhI, containing two similar asymmetric nitrogen atoms, like tar- taric acid, exists in two inactive forms, but so far neither has been resolved into active components. When an asymmetric nitrogen atom is introduced into a compound already con- taining an asymmetric carbon atom, two stereoisomerides are formed, just as two products are formed when a new asym- metric carbon atom is introduced into an active compound. One of the simplest spatial arrangements of the radicals attached to a quinquevalent nitrogen atom is that suggested by Bischoff and accepted by Jones. The nitrogen atom is supposed to be situated at the centre of a pyramid on a rect- angular base, and the five radicals at the five solid angles, the four alkyl groups occupying the four angles of the base, and the acid radical occupying the angle at the apex. Since the three radicals in a tertiary amine all lie in one place, it follows that in the conversion of a tertiary amine into a quaternary ammonium salt a change of "valency direction" occurs. The equilibrium positions of the radicals in the tervalent nitrogen compound are disturbed, and new positions must be found, which for any four alkyl groups must be determined jointly by the forces between these radicals and the nitrogen atom, and the mutual forces exerted by the groups on one another; consequently there will be some definite spatial arrangement around the nitrogen atom. The fifth group, which is always different in character from the other four, will always bear approximately the same relation to each of 634 XLVI. STEREO-CHEMISTRY OF SULPHUR, ETC. these four groups; in other words, it occupies the apex of the pyramid, and it is improbable that it should ever take the place of an alkyl group at the base of the pyramid. The relative positions of the four alkyl radicals at the base of the pyramid is fixed by the forces exerted by these radicals on one another. F. Phosphorus Compounds. Meisenheimer and Lichtenstadt (B. 1911, 44, 356) have obtained methylethylphenylphosphine oxide, 0:PMeEtPh, in optically active forms. The base was prepared by combining methyl iodide with ethyldiphenyl- phosphine, liberating the base with moist silver oxide and then distilling, and was resolved by means of d-bromocamphor- sulphonic acid. The base has [a] D -f- 33 '8 in benzene solution. Somewhat similar experiments of Caven (J. C. S. 1902, 1362) and Ephraim (B. 1911, 44, 631) have given negative results. G. Cobalt Compounds. Werner (B. 1911, 44, 1887, 2445, 3272, 3279) has obtained optically active derivatives of cobalt. It is pointed out that compounds like CoA 3 BCD, CoABC 2 D 2 or CoABC 4 should exist in optically active isomerides, pro- vided the cobalt atoms occupy the centre of an octahedron and the six radicals are situated at the solid angles, e.g.: Such active isomerides have been isolated in the case of l-chloro(or bromo)-2-ammine-diethylenediamine-cobaltic salts, [CoBrNHgenJBr 2 , where C 2 and D 2 are replaced by divalent ethylenediamme radicals (NH 2 .CH 2 CH 2 -NH 2 :). The reso- lution was effected by means of <2-bromocamphorsulphonic acid, and the active salts obtained were quite stable. Similar cases of isomerism have been met with in the case of chromium derivatives (Werner, ibid., 3132, cf. also A. 386, 1). For stereo - isomeric platinum-derivatives, see Kirmreuther, B. 44, 3115. H. Carbon Compounds, with Semicyclic Double Linkings. Many years ago van't Hoff predicted that compounds of the allene type, ^>C:C:C<^f, should exist in optically active modifications. Attempts by Lapworth and Wechsler (J. C. 8. 1910, 38) to obtain such compounds in optically active forms have not met with success. Perkin and Pope (J. C. S. 1906, fcOILING-POINT 636 1075; 1909, 1789; 1911, 1510), however, have succeeded in resolving l-methylcyclohexylidene-4-acetic acid, into optically active components by means of its brucine salt. The two forms have m.-pt. 52-5-53 and [a] D 81 in ethyl alcohol. This resolution is of interest, as the formula does not contain an asymmetric carbon atom, although the mole- cule as a whole is asymmetric. By the addition of bromine to the d- and Z-acids, it has been found possible to obtain four optically active dibromides. An example of somewhat the same type is met with in the oxime of cyclohexan-l-one-4-carboxylic acid, which has been resolved by Mills and Bain (J. C. S. 1910, 1866) into active forms by means of morphine or quinine. Two active sodium salts were obtained, but when acidified with hydrochloric acid an inactive acid was formed. This resolution is used as a strong argument in favour of Hantzsch and Werner's view (p. 138) that when a tervalent nitrogen atom is attached by a double linking to carbon the three valencies of the nitrogen do not lie in. a single plane. If all three valencies were in the same plane the formula for the oxime would contain a plane of symmetry and should not be resolvable. Azobenzene (p. 396) also appears to exist in two stereoiso- meric forms (G&rntner, J. A. C. S. 1910, 32, 1294), viz. red prisms, m.-pt. 68, and orange-red needles, m.-pt. 25, which are represented by anti and syn configurations. XLVII. RELATIONSHIPS BETWEEN PHYSICAL PRO- PERTIES AND CHEMICAL CONSTITUTION A. Boiling-point. Attention has been repeatedly drawn to the fact that in any homologous series the boiling-point tends to increase with the number of carbon atoms present (see pp. 31, 66, HI). 636 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION In the majority of cases the increase in boiling-point for each additional CH 2 is not constant, but tends to decrease with increasing molecular weight (e.g. fatty acids, and espe- cially the paraffin hydrocarbons and alkyl haloids). In the case of the ethyl esters of the normal fatty acids the y ac CH 2 increase is fairly constant, and is about 21 for a CH 2 group (Kopp,W2),W> Difference. Ethyl formate ................ 54-5 Ethyl acetate ................. 77 _ Ethyl propionate ............ 98 Ethyl butyrate ............... 120 Ethyl valerate ............... 144-5 " Ethyl hexoate ................ 167 < Ethyl heptoate ............... 188 *L Ethyl octoate ................. 208 * Ethyl nonoate ................ 228 With the alkyl chlorides the difference between methyl and ethyl chlorides is 35, and this difference diminishes by 2 for each subsequent homologue, so that the difference between heptyl and octyl chlorides is only 23 (Schorlemmer). Attempts have been made to find a general law for the diminution of the difference in boiling-point with increase in molecular complexity. Goldstein suggested the formula p 380 + (n - 1) 19 - 340-9 for the boiling-points of the normal hydrocarbons, where n the number of carbon atoms; this gives good results up to C 12 H 26 , but not beyond. (Compare also Mills, Phil. Mag. [5], 17, 180.) A comparison of isomeric substances shows that the boiling- points can vary considerably, even when the isomerides belong to the same series, e.g. the amyl alcohols : CH 3 (CH 2 ) 3 .CH 2 .OH, 137; (CH 3 ) 2 CH.CH 2 .CH 2 .OH, 131-6; CH 3 .CH 2 .CH(CH 3 ).CH 2 .OH, 128*; CH 3 (CH 2 ) 2 .CH(CH 3 )OH, 118-5; CH 3 .CH 2 .CH(OH).CH 2 .CH 3 , 116'5; (CH 3 ) 2 CH-(CH 3 ).OH, 112-5. In all such cases the normal compound has the highest boiling-point, and the more branched the carbon chain BOILING-POINT 637 becomes, the lower is the boiling-point. Generally there is a difference of 7 between the boiling-points of a pair of isomeric compounds of the type CH 3 CH 2 . CH 2 . X and (CH 3 ) 2 .CH.X. According to Menschutkin> in a group of isomeric alcohols, amines, or amides, the boiling-point falls as the side chain approaches the hydroxy- or amino-substituent. A comparison of isomeric esters, e.g. : n-Butyl acetate, CH 3 .(X).OC 4 H 9 , 124; n-Propyl propionate, CH 3 .CH 2 .CO-O-C 3 H r , 122'4; Ethyl rc-butyrate, CH 3 .CH 2 .CH 2 .CO.O.C 2 H 5 , 121; Methyl n-valerate, CH 3 .(CH 2 ) 3 .CO.OCH 3 , 127, shows that the boiling-point is lower the nearer the oxygen atoms are to the middle of the carbon chain. A remarkable feature is the relatively high boiling-points of hydroxylic compounds when compared with their isomerides or with closely related compounds. As an example, the n -acid isomeric with the last -mentioned group of esters, namely w-hexoic acid, boils at 205. A similar relationship can be shown by the comparison of an alcohol with the ethers isomeric with it. Similarly, a comparison of the boiling- points of the ethyl-derivatives, C 2 H 6 , C 2 H 5 .OH, C 2 H 5 C1, C 2 H 5 Br, C 2 H 5 NH 2 , C 2 H 5 .QEt, C 2 H 5 .CN, indicates the enor- mous effect of the hydroxyl group on the boiling-point, or, again, a comparison of the boiling-point of an acid with those of its chloride, esters, anhydride, or nitrile. The effect of the introduction of halogen atoms has already been referred to (p. 56). The introduction of an atom of chlorine for hydrogen often raises the boiling-point some 60, an atom of bromine about 84, and an atom of iodine 110; and the introduction of a second or third chlorine atom further raises the boiling-point, but not to the same extent. Extremely interesting is the fact that a saturated compound and its ethylene analogue have very nearly the same boiling- points (cf. propyl and allyl alcohols, both 97; G^H 16 and C r H 14 , both 99; propionic acid, 1407; and acrylic acid, 140), although they differ considerably as regards most of their other physical characteristics. Further, methyl ketones, acetyl esters, and corresponding acid chlorides boil at very nearly the same temperature, e.g. acetone, methyl acetate, and acetyl chloride at 55-56; propyl methyl ketone, methyl butyrate, and butyryl chloride at 101-105 (Schroder, B. 1883, 16, 1312). 638 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION B. Melting-point Although, on the whole, in any homo- logous series the melting-points of the solid members tend to rise with increase in molecular complexity, in many series an alternating rise and fall is met with, the members containing an even number of carbon atoms melting at relatively higher temperatures than those with an odd number. This is the case with the higher fatty acids, as is readily seen when the melting-points are plotted against the number of carbon atoms. 40- 1 30- / / 20 / 1 10H / r I / ^ a o ] i / j\ tt> S -10 1 / \ / / \ 3-20. I / 1 n -30 1 , \ / \ / | -40. fl I -50. tir Hn T/t 1 1 1 ] L 2 3 4 & 6 ; ' i } 1 1 1 1 2 No. of Carbon Atoms Many other series show a similar relationship, e.g. succinic acid and its homologues, where the melting-points are : C 180; GO 97; C* 148; C r , 103; C & 140; C 9 , 106; C 10 , 127. (Compare also Beach, Zeit. phys. 1904, 50, 43.) In the case of a group of closely related isomeric compounds it is found that the melting-point tends to rise with the number of side chains or branches, e.g. CH 3 CH 2 CH 2 .CH 2 OH is a liquid, and C(CH 3 ) 3 .OH melts at 25; or again, glutaric acid melts at 97, methyl-succinic at 112, and dimethyl-malonic at 117. The conversion of an acid into an ester always produces a lowering of the melting-point, and the methyl ester always has the highest melting-point of any of the esters derived from a given acid; in fact, in many cases the methyl esters MOLECULAR VOLUME 639 are solids, and the ethyl and higher esters liquids at the ordinary temperature. In the aromatic series it is found that of the isomeric 0-, ra-, and ^-compounds the para- has the highest melting-point. G. Schultz (A. 1881, 207, 362) has also shown that in the group of compounds, Nitro * azoxy * azo hydrazo amine, the melting-point increases up to the azo-compound, and then falls again to the amine. According to Franchimont (Rec. 1897, 16, 126), the melting-point of an organic compound is invariably raised when two hydrogen atoms attached to the same carbon are replaced by oxygen, or when a hydrogen atom is replaced by hydroxyl; cf. C 6 H 5 CH 2 OH and CJEL- CO- OH, or C 6 H 6 and C 6 H 5 .QH. C. Molecular Volume. The relationships between specific gravity and chemical constitution are not so marked as in the case of other physical properties. Attention has already been drawn to the fact that in a homologous series the specific gravity either decreases with an increase in the number of carbon atoms, and tends to reach a minimum value (p. 141), or increases with the number of carbon atoms and tends to attain a maximum (p. 31). More interesting results have been obtained by an exami- nation of molecular volumes, i.e. the quantity mo e u ar wei g t specific gravity Kopp (1842) determined the molecular volumes of a number of carbon compounds, and came to the conclusion that in the case of closely related compounds the same difference in com- position corresponds with a similar difference in molecular volume, e.g. : Mol. volume. Difference. Alcohols, CHo-OH ............... 42'2 on C 2 H 6 -OH ............... 62-2 20 C 3 H 7 .OH ............... 81-34 H ............... 101-58 ~ Fatty acids, H.CO 2 H ............... 41'4 CH 3 .C0 2 H ............ 63-7 ^ *** C 2 H 5 .C0 2 H ............ 85-4 |{4 C 3 H r .C0 2 H ............ 107-1 and further, that isomeric liquids have the same molecular volumes, e.g. acetic acid 63 -7, and methyl formate 63 -4; pro- pionic acid 85-4, ethyl formate 85 -3, and methyl acetate 84-8. 640 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION The replacement of an atom of oxygen or an atom of carbon by two atoms of hydrogen does not appear to alter the mole cular volume to any considerable extent : Methyl alcohol, CH 4 O.... 421 Formic acid, CH 2 O 2 41'4 Benzy 1 alcohol, C 7 H 8 O... 1237 Amyl alcohol, C 6 H 12 O .... 124'0 Ether, C 4 H 10 O 106-0 Butyric acid, C 4 H 8 O 2 107'1 The difference due to a CH 2 group is roughly 22, and since the atomic volume of carbon is twice the atomic volume of hydrogen, it follows that the atomic volume of carbon =11 and of hydrogen = 5*5. Kopp also indicated that the atomic volume of a polyvalent element, e.g. oxygen, is not a constant quantity, but varies according to the manner in which the oxygen atom is united to the other atoms in the molecule. Thus in the form of a carbonyl group, ^>C:0, the atomic volume of oxygen is 12 '2 (carbonyl oxygen), but in the form of ^C0'C^ or ^C0H (oxidic oxygen) it has the value 7 '8. Similarly, Schiff has shown that the carbon atom can have different values according as it is united to another carbon atom by a single, double, or triple bond. Thus each double bond causes an increase of four units in the molecular volume. By means of these atomic volumes it is possible to calculate the molecular volume of any simple carbon com- pound, e.g. ethyl formate, H-CO'O'CH^CHg, 30 = 33 ^ 6H = 33 I . n 10: = 12-2 f = 860 l.Q. = 7-8J and the value actually obtained by experiment is 85-86. Although such generalizations as those mentioned are of considerable theoretical importance, the method is not one which has been used to any great extent for determining the constitution of chemical compounds (compare molecular refraction and molecular magnetic rotation). This is partly due to the fact that the specific gravity, and hence the mole- cular volume, varies with the temperature. At first, Kopp made all his determinations at 0, but obtained better results by taking the specific gravity at the boiling-point of the liquid. It is not necessary to actually make the determin- ation at the boiling-point, but to determine the specific gravity MOLECULAR REFRACTION 641 at a lower temperature, and then to correct for the coefficient of expansion as determined by the dilatometer. In reality, the determinations should be made at temperatures when the liquids are all in an exactly comparable condition, viz. at the critical point (compare Zeit. phys. 1890, 6, 578). More recent determinations of molecular volumes by T. E. Thorpe (J. C. S. 1880, 327) indicate that isomeric compounds have not always the same molecular volumes, and that the differences amount to several units per cent, but that elements such as chlorine and bromine in the liquid state have the same atomic volumes as in their organic compounds (compare also Lossen, A. 1883, 214, 138; Horstmann, B. 1885, 20, 766; Sehi/, A. 1884, 220, 71; Zahnder, A. 1883, 214, 138). D. Molecular Refraction. It has been shown that the molecular refraction, like the molecular volume, is to a large extent an additive property, i.e. the molecular refraction is the sum of the atomic refractions of the atoms present in the molecule, but, in addition, that it is to a certain extent consti- tutive; thus the oxygen atom has distinct atomic refractions according to whether it is in the carbonyl or oxidic state of combination. m, r ,. . j ., ir sine of angle of incidence The refractive index itself, n = , ^ -. ? : , sine of angle of refraction does not lend itself to the study of generalizations, but, according to Gladstone and Dale (1858), such generalizations 77 - T are found when the specific refractory power, (where d = specific gravity), is employed. This specific refraction varies but little with the temperature; thus with water: t o io" 20 90 100 Specific refraction... 0'3338 0'3338 0'3336 0'3321 0'3323 and is not largely affected by the presence of other substances. A second formula for the specific refractive power has been o i introduced by Lorentz and Lorenz, viz. n ~ w ; this has the (TI -f" 2)a advantage that the value appears to be independent of the physical state of the compound: Lorentz- Lorenz Gladstone- Dale t Gas. Liquid. Gas. Liquid. Water 10 0*2068 0'2062 O'SlOl 0-3338 Carbon disulphide 10 0'2898 0-2805 0*4347 0-4977 Chloroform 10 0'1796 01790 0'2694 0-3000 642 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION When the refractive powers of different substances are com- pared, it is usual to employ the molecular refractive powers rather than the specific refractions. The molecular refraction is the product of the specific refraction into the molecular weight; according to Gladstone ^ n ~" ', and according to As the refractive index differs with light of different wave- lengths, it is necessary to determine the value of n for mono- chromatic light, and to indicate the special light employed; generally determinations are made for the D line in the sodium, or the a line in the hydrogen spectrum, and are carried out in hollow prisms containing the liquid and pro- vided with sides of plate glass. Landolt examined the molecular refractions of the members of several homologous series, and came to the conclusion that the molecular refraction is an additive quantity, and that similar changes in composition induce similar changes in the molecular refractive power: Alcohols M(n-l) d Diff. CH,-OH 13-17 OH ........ 20-70 7-53 -> 7-60 Acids Diff. H-CO 2 H 13-91 CH 3 .C0 2 H 21-11 C 2 H 6 -C0 2 H 28-57 C 3 H 7 .C0 2 H 36-22 44-05 C 3 H r .OH 28-30 _ ,_ Q1 C 4 H 9 .OH 36-11 * Zji C 6 H n .OH 43-38" and similarly for various groups of esters, the mean value for the CH 2 group being 7 '6 units. By methods similar to those described under molecular volumes, values were obtained for the atomic refractive powers of the elements for the a line, e.g. C = 5, H = 1-3, = 3, Cl = 9-79, Br = 15-34, &c. The values thus obtained for the halogens are practically identical with those determined for the elements in the free state. The molecular refraction of any simple carbon compound can be calculated by adding together the atomic refractions of the constituent elements. Thus, for ethyl alcohol, C 2 H 6 0, the calculated molecular refraction is 2x5 + 6x1*3 + 3 = 2O8, and that actually found experimentally is 20*7. According to Landolt, the molecular refraction is purely additive, and thus isomeric compounds should possess identical molecular refractive powers. This is largely true in certain MOLECULAR REFRACTION 643 cases, e.g. the compounds C 3 H 6 3 propionic acid," 28-57: methyl acetate, 29-36; and ethyl formate, 29-18. In a series of investigations begun in 1878 (A. 1879, 200, 139; 1880, 203, 1 and 255) Bruhl has examined the influence of atomic grouping on the molecular refraction, and has been able to show that the property is not purely additive, but to a certain extent constitutive. Thus a comparison of the experi- mental and calculated values for unsaturated and the corre- sponding saturated compounds at once exhibits anomalies : . for a-line. Observed. Calculated. Difference. Allyl alcohol, C 3 H 6 ............ 27'88 25'8 2'08 Propyl alcohol, C 3 H 8 .......... 28'60 28'4 0'2 Similarly in other unsaturated compounds it is found that a double bond between two carbon atoms usually increases the molecular refraction by about two units (mean value 2-15), and a triple bond by T95 unit. Other polyvalent elements have atomic refractions which vary with their state of combination; thus oxygen in carbonyl compounds has the value 3-4 in hydroxy-derivatives, and in ethers the value 2-8. The following is a list of some of the more important atomic refractions used by Gladstone and by Bruhl: Briihl Gladstone. (L.-L. formula). Carbon in saturated compounds ......... 5-0 2 -365 Hydrogen ..................................... 1-3 T103 Carbonyl oxygen in ^>C:O ............... 3'4 2*328 Ether oxygen in C-O-C ............. 2'8 1'655 Hydroxylic oxygen in ^C-O-H ........ 2*8 1-506 Chlorine ....................................... 9'9 6'014 Bromine ....................................... 15'3 8'863 Iodine ......................... ................. 24*5 13'808 Ethylenebond ............................... 2'1 1'836 Acetylene bond .............................. T95 2'22 Sulphur in C:S .............................. 16'0 Sulphur in C-S-H .......................... 141 Nitrogen in compounds -^C N<^ ...... ... 2'76 Briihl has employed the molecular refraction for the investi- gation of certain tautomeric substances, e.g. ethyl acetoacetate, 644 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION The observed value for the a line is 31*89, and the values calculated for the ketonic and enolic formulae respectively, 31-53 and 32-55: CH 3 CO CH 2 CO OC 2 H 5 60 = 14-190 10H = 11-03 2O (carbonyl) = 4'656 10 (ether) = 1'655 31-531 CH 3 C(OH) : CH CO OC 2 H 5 60 = 14-190 1 ethylene bond = 1'836 10H = 11-03 1O (carbonyl) = 2'328 1O (ether) = 1-655 lO(hydroxyl) = 1-506 32-545 The conclusion to be drawn from these numbers is that the ethyl acetoacetate at the ordinary temperature consists mainly of the ketonic form, but probably contains a small amount of the enolic. Bruhl also tests the purity of numerous com- pounds prepared by him, by means of molecular refraction and dispersion determinations in place of ordinary combustions. Perkin and Gladstone have examined the molecular refractive powers of several di- and triketonic substances. Thus, for acetylacetone at 11, using the formula ^ M for the a line, the value 45-17 was obtained, and this decreased to 44*14 at 99*3. The ketonic formula requires 42*2, the mono-enolic 43*7, and the di-enolic 45-2. At 11 the diketone undoubtedly consists mainly of the dihydroxylic compound CH 3 C(OH): C:C(OH)-CH 3 , and at the higher temperature, probably of a mixture of the mono- and dihydroxylic forms. Schaum has also used the method to show that reagents like sodic ethoxide or piperidine have no enolizing or ketonizing actions on ethyl acetoacetate, as in presence of both these compounds the molecular refraction is 32 for the sodium line Compounds which have a strong dispersive power do not appear to lend themselves to the calculation of molecular rotation in the manner just described. E. Molecular Magnetic Rotation, This is quite distinct from the ordinary optical activity exhibited by substances with asymmetric molecules, and is common to practically all substances when they are examined by means of a polarimeter in a strong magnetic field. The tube containing the liquid to be examined is placed end on between the two poles of an electro-magnet, these poles being pierced in order that the ob MOLECULAR MAGNETIC ROTATION 645 server may take readings, and the apparatus is often jacketed in order that the temperature may be kept constant. (For new form of apparatus, see J. C. S. 1906, 608.) When the magnetic field is changed, it is found that the amount of rotation remains the same but changes sign, and in each determination several positive and several negative readings are made. The rotations of all substances are compared with water under the same conditions, and thus the molecular magnetic rotation is LJ, where M is the molecular weight Loa^d of the substance, a its observed rotation using a column of liquid I cm. long, and d the specific gravity of the liquid; 18 is the molecular weight of water, c^ its observed rotation, d 1 its density, and / x the length of column used. As a rule I = I-L and d-i = 1 (approx.). An examination of different homologous series by W. H. Perkin, Sen., showed that for an increase of CH 2 in the molecule there is usually an increase of 1-023 units in the molecular magnetic rotation. At first, Perkin attempted to obtain atomic magnetic rotations for each element in the same manner as already described for atomic volumes and atomic refractions; the values so obtained gave good results with several distinct series, but could not be applied generally. The method of using series constants was then adopted. The molecular magnetic rotation r of a com- pound may be represented as: r = C + 7i 1-023. Where C is a constant which varies with different homolo- gous series, n is the number of carbon atoms present. A few of the constants are : n-Parafnns 0'513 wo-Paraffins 0-631 n- Alcohols 0-699 iso- Alcohols 0-844 n- Fatty acids 0'391 Higher esters 0'337 Aldehydes 0'263 Alkyl chlorides 1'988 Alkyl bromides 3'816 Alkyl iodides 8-011 Alkyl acetates '370 If in any series it is required to calculate the molecular magnetic rotation of a member, this is readily accomplished by adding n x 1'023 to the series constant; thus for ?i-nononic acid we have 0-391 + 9 X 1-023 = 9-598, and the value actually found by experiment is 9-600. 646 XLVII, PHYSICAL PROPERTIES AND CONSTITUTION There is usually a definite relationship between the values for an unsaturated compound and its saturated analogue, e.g.: Diff. Ethyl crotonate. . . 7 '589 , , , 9 Ethyl butyrate.... 6'477 J Diff. Ethyl oleate 21-909 -, ,, 9 Ethyl stearate... 20797 J With allyl compounds the difference is not so great; thus the difference between allyl alcohol, 4 -682, and propyl alcohol, 3 -768, is only 0-914, and similarly for other allyl compounds. These facts have been used as arguments in the determina- tion of the constitution of undecylenic acid (J. C. S. 1886, 205). The difference in molecular magnetic rotation between unde- cylenic acid, C 10 H 19 'C0 2 H, and undecylic acid, C^H^-COgH, is 0*897, and similarly for the esters the difference is 0"890. It is argued that this difference approximates to 0*91, the usual difference between an allyl compound and the corresponding saturated derivative, and hence undecylenic acid is presumably an allyl derivative with the formula CH 2 : CH[CH 2 ] 8 - C0 2 H. The molecular magnetic rotation of a complex compound can be calculated by taking as the series constant the mean of the series constants of the various groups of compounds which it represents. Thus ethyl lactate, CH 3 .CH(OH)-C0 2 C 2 H 5 , pos- sesses the groupings characteristic of an ethyl ester and also of a secondary alcohol; the series constants for these are: Ethyl ester = 0'337; secondary alcohol = 0'844. Mean = 0'590. The series constant for ethyl lactate and homologues is thus 0-590, and the molecular magnetic rotation of the lactate 5 X 1-023 -f 0-590 = 5'705, which agrees very well with the experimental value, 5-720. The values of their molecular magnetic rotations have been used by Perlcin in discussions on the constitutions of certain tautomeric compounds, especially those of the keto-enolic type. In the case of ethyl acetoacetate, the molecular magnetic rotation for the ketonic form may be calculated as follows: Series constant for alkyl acetate 0'370 Series constant for ketone 0'375 Mean 0'372 Molecular rotation = 6 X T023 + 0'372 = 6-510. For the enolic form ethyl /3-hydroxy-crotonate, CH 3 C(OH): ABSORPTION SPECTRA 64? CH'C0 2 C 2 H 5 the molecular rotation may be calculated by the two following methods: 1. Molecular rotation of ethyl crotonate 7'589 OH replacing H as in alcohol 0'194 Molecular rotation of ethyl hydroxy-crotonate 7 '783 2. Mol ecular rotation for ethyl -hydroxy-butyrate 6 '737 Difference between unsaturated and corresponding satu-) 1.110 rated compound / Molecular rotation for ethyl hydroxy-crotonate 7 '849 The experimental value actually found for ethyl acetoacetate at the ordinary temperature is 6 '501, and this indicates that, at this temperature, the ester consists essentially of the keto- f orm. Some general conclusions drawn by Perkin. are : (i) That monoketonic compounds and keto- esters, which react as tautomeric substances, as a rule, have the ketonic and not the enolic structure, except when a number of negative groups, such as phenyl and car boxethyl, C0 2 C 2 H 5 , are present. These have an enolizing tendency, as shown in ethyl benzoyl- acetate, C 6 H 5 CO CH 2 C0 2 C 2 H 5 , which, according to Perkin, is a mixture of some 75 per cent of the keto- and 25 per cent enolic compound. (ii) Acetylacetone at 17 consists of a mixture of some 80 per cent of the hydroxy-ketone, CH 3 -CO.CH:C(OH).CH 3 , and some 20 per cent of the dienolic form, CH 3 C(OH):C: C(OH)CH 3 . If alkyl radicals replace the hydrogen atoms of the methylene group of acetylacetone, the tendency to form the enolic form is less marked, whereas the introduction of negative groups, 'COgEt, increases the tendency. (iii) Rise of temperature favours ketonization. (For full details, see J. C. S. 1884, 421; 1886, 205, 777; 1887, 362, 808; 1888, 561, 695; 1889, 680; 1891, 981; 1892, 800; 1893,488; 1894,402,815; 1895,255; 1896,1025; 1900, 267; 1902, 177, 292.) F. Absorption Spectra. Ostwald (Zeit. phys. 1892, 9, 579) has studied the absorption spectra of groups of closely related coloured compounds, e.g. a series of soluble metallic perman- ganates, various salts of fluorescein, eosin, and rosolic acid, and has been able to show that, in dilute solutions, the absorption spectrum of a salt is the sum of the spectra of the ions; thus all the permanganates gave practically the same absorption due to the Mn 2 8 ion. 648 XLVIL PHYSICAL PROPERTIES AND CONSTITUTION Hartley and others have carried out numerous investigations on ultra-violet absorption spectra of carbon compounds, and extremely important relationships have been established. (For references, see B. A. Reports mentioned in Preface.) Hartley photographed the spark spectrum of an alloy of tin, lead, cadmium, and bismuth after it had passed through a solution of the substance under examination. It was found that practically all open-chain and even the closed-chain poly- methylene compounds give no distinct selective absorption; they are remarkably transparent to ultra-violet rays. Numerous exceptions, e.g. ethyl acetoacetate derivatives, ke tones, and practically all ketonic compounds, whether open- chain or cyclic, have since been met with (Baly and Desch, J. C. S. 1904, 1039). In any given series, e.g. the alcohols, it is usually found that each increment of CH 2 produces a slight increase in the absorption of the more refrangible rays. Benzene derivatives, naphthalene, anthracene, phenanthrene, and their derivatives, also pyridine, quinoline, dimethylpyrazin, N^QjjfQ-jyj-^N, in alcoholic or aqueous solutions, exhibit, in many cases, distinct absorption bands. Most of the terpenes, furane, thiophene and pyrrole derivatives, piperidene and re- duced benzene derivatives, resemble the aliphatic compounds. In all cases Hartley examined the absorption for solutions of very different concentrations, always increasing the dilution until complete transmission was obtained. He also used layers of the given solutions of different lengths, and then plotted the results in the form of curves, putting the oscillation frequencies (reciprocal of wave-lengths) as abscissae, and equivalent thick- nesses of solution as ordinates. Thus with two solutions, one 01 N and the second -001 N, and using layers of each 30, 20, 15, 10, 5 mm. thick, the equivalent thicknesses are 300, 200, 150, 100, 50, 30, 20, 15, 10, and 5, and these numbers are used in the plotting. Baly and Desch have used the iron arc spectrum and a glass cell with quartz ends for containing the solution, so arranged that the length of the column of liquid can easily be varied. They also plot the oscillation frequencies against the logarithms of the relative thicknesses of liquid. It is claimed that from the absorption curves so plotted it is very much easier to compare the relative persistence of the absorption bands. Hartley examined a number of isomeric benzene derivatives, e.g. xylenes, cresols, and dihydroxy-benzenes, and found that ABSORPTION SPECTRA 649 the oscillation frequency of the extreme rays transmitted follows the order ortho * meta > para, i.e. the para-com- pounds exhibit the greatest absorption. The same generaliza- tion does not hold for other groups of compounds, e.g. the hydroxy-benzoic acids. A most important fact is that the introduction of a methyl group for a hydrogen atom affects the absorption spectrum but little; as a rule, it slightly increases the general absorption, but does not alter the general character of the spectrum, e.g. benzene and toluene, benzoic acid and methyl benzoate. This fact has been largely used by Hartley and Dobbie in discussions on the constitution of certain tautomeric substances, more especially those of the lactam-lactim type. A study of the general chemical properties of isatin (p. 523) does not render it possible to say whether this compound has the lactam constitution I, or the lactim constitution II: I C 6 H 4 <>00 II C 6 H 4 <*g>C.OH. Isatin gives rise to the two distinct methyl ethers : (a) methyl- isatin, III, a solid melting at 101, readily hydrolysed, and obtained by the action of methyl iodide on silver isatin; (b) pseudo- methyl -isatin, IV, a solid melting at 134, not readily hydrolysed, and prepared by heating methyl-dibromo- oxindole with water: III CHC.OCH IV An examination of the absorption curves of the three com- pounds, isatin, methyl-isatin, and pseudo-methyl-isatin (J. C. S. 1899, 640), shows that the curves for isatin and the pseudo- ether are practically identical, both possessing two bands of similar intensity and differing considerably from that of methyl-isatin, which consists of a single band. There can be no question but that isatin itself has a constitution similar to that of the pseudo-methyl ether; and since the reactions of this prove beyond doubt that it is a nitrogen and not an oxygen ether, isatin must have the lactam constitution repre- sented by formula I. Similarly carbostyril (p. 541), by a com- parison of its absorption curve with that of its two methyl ethers, can be shown to possess the lactam constitution I and not the lactim constitution II : 650 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION and o-oxycarbanil, obtained by fusing o-amino-phenol hydro- chloride with carbamide, has an absorption spectrum practi- cally identical with that of its N-ethyl ether, and hence has the lactam constitution C 6 H 4 <Q^>CO. Hartley and DdbUe (J. C. S. 1900, 498) have also examined the absorption spectra of the three dibenzoyl-succinates ob- tained by Knorr. According to the latter, the a-compound has the enolic constitution I, whereas the two solid /3- and y-com- pounds are stereo-isomeric ketones with constitution II : OH CPh : C CO 2 Et COPh - CH . CO 2 Et 1 OH.CPh:C-CO 2 Et l COPh CH 00 2 Et In accord with this view is the fact that the /3- and y-com- pounds give practically the same spectrum, which differs, how- ever, considerably from that of the a-compound. The trans- formation of the a- into a mixture of the /?- and y-compounds can readily be followed by examining alcoholic solutions at different intervals of time; at the end of three hours, consider- able change has taken place, and at the end of three weeks the ketonization is practically complete. Baly and Descli have found that although ethyl aceto- acetate in dilute solution, and its two ethyl derivatives, CH 3 .CO.CHEt.C0 2 Et and CH 3 . C(OEt) : CH . C0 2 Et, give no selective but only general absorption, the metallic derivatives, e.g. ethyl sodio-acetoacetate, have distinct banded absorption spectra, and that even the addition of a small amount of alkali to ethyl acetoacetate produces a banded spectrum. Acetyl- acetone itself and its aluminium, beryllium, and thorium deri- vatives all give banded ultra-violet absorption spectra. Since neither the C- nor the 0-ethyl derivative of ethyl acetoacetate produces selective absorption, it would appear that the char- acteristic band in open -chain compounds cannot be due to either the ketonic or the enolic constitution, and Baly and Desch draw the conclusion that these absorption bands are only produced by compounds which are in an actual state of change, for example, passing alternately from the ketonic to the enolic form; in all cases valency changes (desmotropism), and in particular cases, e.g. keto-enolic compounds, a wander- ing of a labile atom (tautomerism) occur. Within certain limits the same type of valency change produces an ultra- violet absorption band in the same position, although the ABSORPTION SPECTRA 651 compounds undergoing change may contain elements of very different atomic weights, e.g. hydrogen, sodium, aluminium, thorium; the vibrations in the molecule which synchronize with the oscillation frequency of the rays absorbed cannot, therefore, be the vibration of the labile atoms themselves, but may be due to the change of linking (J. C. S. 1905, 768), i.e. according to the electronic theory to the vibrations of the valency electrons. The persistence of the band over a definite range of concentration is taken as a measure of the relative number of molecules which are actually undergoing change. The absorption bands characteristic of simple benzene deri- vatives may be accounted for in a somewhat similar manner (J. C. S. 1904, 1029; 1905, 1331). In the case of simple benzene derivatives, especially hydrocarbons, seven distinct bands are visible, due to seven distinct valency changes. (Compare also J. C. S. 1906, 514, 983; 1907, 449, 1122; 1908, 1906; 1910, 571, 1337, 1494.) Baly and Stewart (ibid. 1906, 489, 502, 618) have examined the absorption curves of various ketones and quinones. Their results with fairly concentrated solutions show that the ketones which show the most persistent absorption bands are those which are most reactive from a chemical point of view, e.g. react most readily with sodium hydrogen sulphite or with hydroxylamine. In these cases also, the bands are attributed to actual valency changes (desmotropism) going on in the molecules of the substances. With /3-diketones and mono- ketones the change is between the keto- and enolic forms. It is well known that the entrance of substituents into the acetone molecule tends to diminish its reactivity, a pheno- menon which for several years has been attributed to steric hindrance (pp. 175, 449). Baly and Stewart object to this view, since it does not account for the increased reactivity of ethyl acetoacetate as compared with acetone, or more especially with methylethyl ketone. The relative reactivities of the three compounds are indicated by the following numbers: Methylethyl ketone, 22*5; acetone, 39 '7; ethyl acetoacetate, 47 '0, which give the percentage amount of each compound transformed into its bisulphite derivative after twenty minutes. The ordinary theory of steric hindrance would lead us to expect that ethyl acetoacetate would be less reactive than acetone, since it contains the relatively large substituent C0 2 Et. Since ketones, when arranged according to their reactivities, and according to the persistence of their absorp- 652 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION tion bands, follow the same order, there would appear to be a simple relationship between the two properties; and accord- ing to Baly and Stewart both are due to the same cause, namely, the extent to which tautomeric or desmotropic change occurs in the molecule. In the case of the keto-enolic com- pounds, R.CO.CH 2 R' z E.C(OH):CHK', the carbonyl group is supposed to be in a specially reactive state during the change in fact, to be in a condition com- parable with what is usually termed the nascent state in the case of the elements. The introduction of substituents, as a rule, lessens the amount of tautomeric change occurring in the molecule, and thus lessens its chemical reactivity. The intro- duction of the carbethoxy-group, however, tends to increase the desmotropism, as is shown by a comparison of the absorp- tion curves of concentrated solutions of acetone and of ethyl acetoacetate, and thus the chemical activity of the ketone is increased and not diminished by the introduction of the C0 2 Et group. The enormous reactivity of ethyl pyruvate and its very persistent absorption bands are accounted for by a dynamic change of the type CHg-C-C-OEt ^ CH 3 .C:C.OEt oo 6-6 Quinones also give characteristic absorption bands which are attributed to the change: /CH : CH\ (5.0 -- 0-C = The introduction of substituents into the quinone molecule renders the absorption bands less persistent, and also lessens the chemical reactivity of the compound. An examination of the absorption curves of the nitranilines, where there are persistent bands in the visible part of the spectrum closely resembling those of quinone, leads Baly, Edwards, and Stewart (J. C. S. 1906, 513) to the conclusion that the free amines have a quinonoid structure, ABSORPTION SPECTRA 653 and that tautomeric change of the same type as that de- scribed under the quinones occurs. Their hydrochlorides, on the other hand, have the ordinary benzenoid constitution, N0 2 .C 6 H 4 .NH 2 , HC1. The nitro-phenols give absorption spectra which closely resemble those of their methyl ethers, and would appear to have the benzenoid formula N0 2 C 6 H 4 .OH. The sodium salts, on the other hand, give absorption curves which closely resemble those for the nitranilines, and would thus be repre- sented by the quinoid formula, which would be capable of tautomeric change in much the same manner as quinone. According to Lomy and Desch (J. C. S. 1909, 807), intra- molecular change is not always accompanied by selective absorption. The conversion of normal nitrocamphor into the pseudo-isomeride, a reaction which can be studied quanti- tatively (p. 657), is not accompanied by any characteristic absorption bands, but such bands make their appearance when an alkali is added, and the addition of an excess of alkali does not produce increased absorption. The absorption cannot be due to tautomeric change, as in the presence of the alkali the nitrocamphor exists as a stable sodium salt. The following formulae are suggested (where X = C 8 H 14 ) : ,Q CH.N0 2 yO<- ^ Normal, X- ; pseudo, X<. N-C'H. y C:NO.ONa sodium salt, X<^ Hantzsch (B. 43, 1549), as the result of spectroscopic investi- gations of ethyl acetoacetate and its derivatives, draws the conclusion that the specific absorption observed in solutions cannot be due to the enolic modification, nor yet to an oscil- lation between the ketonic and enolic states, but to an iso- meric aci-form in which the latent valencies of two oxygen atoms are operative, e.g. : CH 3 .C.OH H-C-eb-OEt. The fact that an increase in the amount of alkali produces an 654 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION increase in the selective absorption is attributed to the fact that an excess of alkali prevents the hydrolysis of the sodium salt to the enol and sodium hydroxide. The absorption bands of various vapours, e.g. benzene, py- ridine, furane, and thiophene derivatives, have been studied by Hartley (Phil. Trans. 1908, A. 208, 475) and Purvis (J. C. S. 1910, 692, 1035, 1546, 1648; 1911, 2318), who show that in the form of vapour these compounds give absorption spectra which are much more complex than those of their solutions. The conclusion that ethyl acetoacetate is an equilibrium mixture of the ketonic and enolic modifications a conclusion based mainly on the study of physical properties has been confirmed quite recently by other methods. Of these, the following are the more important: 1. Kn&rr (B. 1911, 44, 1138) has shown that, by cooling to 78 a solution of the ordinary ester in alcohol and ether in an apparatus specially designed to exclude moisture and to maintain a high vacuum, the ketonic form separates as well- defined needles or prisms, m.-pt. 39 and b.-pt. 39-40/ 2 mm. It does not give a coloration with ferric chloride, and does not react with bromine solution. Even at the ordinary tempera- ture it takes several weeks before the equilibrium mixture is again formed. The practically pure enol is obtained by sus- pending the sodium derivative in light petroleum cooled to 78 in a special apparatus, and passing in hydrogen chloride just insufficient for complete decomposition. The solution when filtered and evaporated at 78 yields the enolic ester as a colourless oil, which gives an intense coloration with ferric chloride. At the ordinary temperature it requires ten to four- teen days to again form the equilibrium mixture, but at 100 the change is completed in one minute. By comparing the refractive index of the ordinary ester with the values for mixtures of known concentration, it has been calculated that the equilibrium mixture contains 2 per cent of the enol. 2. By means of experiments made with compounds which exist in stable keto and enolic forms, K. H. Meyer (A. 380, 212; B. 44, 2718) shows that the unsaturated hydroxylic modification reacts instantaneously with an alcoholic solution of bromine, yielding an unstable dibromide, which immediately gives off hydrogen bromide and forms the bromo - ketone. The best method for estimating the amount of enol is to add an excess of the alcoholic bromine solution, to remove the excess by means of /3-naphthol, and then to determine the ANOMALOUS ELECTRIC ABSORPTION 655 amount of bromo-ketone by adding potassium iodide solution, and titrating the liberated iodine by means of standard thio- sulphate : CO-CHBr * CI(OH).CHBr CI(OH).CHI C(OH):CH + L, In this way it has been shown that the ordinary ethyl aceto- acetate contains about 7 per cent of the enol, and the same results are obtained when freshly prepared solutions in various solvents are examined; but such solutions when kept undergo change, e.g. a hexane solution when kept for forty-eight hours at 18 contains nearly equal amounts of keto and enolic modi- fications. A rise in temperature also tends to favour the formation of the ketonic form. In a similar manner acetyl- acetone has been shown to contain 80 per cent of enol. 3. Knorr and Schubert (B. 1911, 44, 2772) use a colori- metric method for estimating enols in allelotropic mixtures, a method which is based on the reaction between the enol and ferric chloride, EH + FeCl 3 = FeRCl 2 + HC1, where R is the enolic residue. The comparison is made with standard solutions prepared by mixing solutions of the pure enol with one of sublimed ferric chloride in molecular pro- portions. G. Anomalous Electric Absorption. P. Drude (B. 1897, 30, 941) has found that numerous organic compounds containing hydroxyl groups are capable of absorbing electric waves of high frequency (about 400 million per second), although they are not good conductors; whereas ordinary non-conductors show no such absorption. The phenomenon is termed by Drude "anomalous electric absorption", and, with the ex- ception of water, all liquid hydroxyl derivatives display this anomalous absorption. The presence of hydroxyl groups cannot always be inferred from the exhibition of anomalous absorption, as a few compounds which contain no hydroxyl groups possess the property to a slight extent. Drude himself applied the method to the examination of certain keto-enolic tautomeric substances. Ethyl acetoacetate itself absorbs but slightly, and is thus presumably mainly the keto-form. Ethyl benzoylacetate and ethyl oxalacetate absorb strongly, and should thus contain considerable percentages of the enols. 656 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION H. Optical Activity. Attention has already been drawn t" the fact that compounds, the molecules of which are asym- metric, are, when in the liquid or dissolved state, optically active, i.e. able to rotate the plane of polarization (p. 154) either to the right (dextro-rotatory) or to the left (Isevo- rotatory). The specific rotatory power [a] of a liquid is obtained by dividing the observed rotation by the length of the column of liquid used and by the specific gravity of the liquid [a] = - -, and the molecular rotation is the product of the specific rotatory power into the molecular weight (M). For a solution : r a ] = 1QQa IQOa _ IQOa X v lXc ~ where c = concentration or number of grams of the active compound in 100 c.c. of solution, d = specific gravity of the solution, p = per cent of active substance in the solution, and g = number of grams of active substance in v c.c. of solution. The specific rotatory power of a solution may often be in- creased enormously by the introduction of an inorganic salt; some of the most effective are boric acid and alkali molybdates and tungstates. As a rule, the nature of the monochromatic light, e.g. sodium light, is indicated, also the temperature and the nature of the solvent, e.g. [a] 1 ^, where D indicates that the number refers to sodium light and that the determination was made at 15. Various attempts have been made to deduce general conclusions bearing upon the amount of rotation and the constitution of the compound. Guye (C. R. 110, 714) has attempted to connect the degree of asymmetry of the molecule of a compound C a, b, c, d with the masses of the four radicals present and the distance of the centre of gravity of the mole- cules from the centre of the tetrahedron (C. E. 1896, 1309; 1898, 181, 307). The researches of P. F.FranEand and others (J. C. S. 1899, 337, 347, 493, &c.) have shown that Guye's conclusions are not of general application. Patterson (J. C. S. 1901, 167, 477; 1902, 1097, 1134; 1904, 765, 1116, 1153; 1905, 122, 313) has made a careful investi- gation of the influence of solvent, temperature, &c., on the optical activity of various substances. He finds that dilute solutions of ethyl tartrate in water, or in methyl, ethyl, or propyl alcohol, possess a higher specific rotation than the pure ester itself, that the specific rotation increases with dilution OPTICAL ACTIVITY 657 until a concentration of 10 grams in 100 grams of solvent is reached, and then the rotation remains practically constant. The highest values are always obtained with aqueous solutions, and the other solutions follow in the order methyl, ethyl, Ti-propyl, isobutyl, and sec-octyl alcohol. The effect of increase of temperature upon corresponding solutions varies somewhat. In water the coefficient is nega- tive for dilute solutions, but in the various alcoholic solutions it is positive, as it is also for the pure ester. According to Patterson the change in specific rotation with solvent or temperature is not to be attributed to association, but rather to the internal pressure of the solvents (compare Abst. 1900, 2, 329). Walden has also conducted numerous investigations on opti- cally active compounds, and concludes that there is a relation- ship of a qualitative nature only between the optical activity of a substance in a given solution and its molecular weight in . that solution. (For a summary of work on optical activity see Walden, B. 1905, 38, 345-409). The polarimetric method has been used by Lowry (J. C. S. 1899, 75, 211) for a quantitative study of the tautomerism or dynamic isomerism of the nitro- and bromo-nitro-camphors. Each of these compounds appears to exist in two distinct forms, one of which contains the nitro-group, >CHN^Q, and the other the isonitro-group, ^>C:NO'OH. Ordinary crystal- line nitro-camphor, melting at 102, is regarded as consisting of the normal form, its homogeneity being vouched for by the constancy of its initial specific rotatory power ([a] D = 124 in 5-per-cent benzene solution), and by its well-defined crystal- line form. When dissolved the nitro-compound at once begins to change into the pseudo form, and this change is accompanied by an alteration in the rotatory power; with the 5-per-cent benzene solution the specific rotatory power has fallen to 104 at the end of four days, and then remains stationary. This solution represents a mixture of the normal and pseudo- compounds in dynamic equilibrium, and assuming that the pseudo-compound, which so far has not been obtained in a pure form, has a specific rotatory power +180 in benzene solution, then the solution, with a rotation of 104, con- tains some 93 per cent of the normal and 7 per cent of the pseudo form, (B4SO) 2T 658 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION The velocity of the transformation, normal * pseudo, is increased by rise of -temperature, by increase in concentration, and by the addition of traces of alkalis. Both the normal and pseudo forms of 7r-bromo-nitro-camphor have been isolated (Lapworth and Kipping, J. C. S. 1896, 304). The compound, melting at 142, when dissolved in benzene, gives an initial specific rotatory power +1S8 , which changes to 38 in a 3'33-per-cent benzene solution, and appears to be the pseudo form. The compound melting at 108 3 shows a change in rotatory power from 51 to 38, and appears to be the normal compound. When either of the two pure compounds is dissolved in benzene, tautomeric change occurs, and a mixture of the two compounds in dynamic equilibrium is obtained. From the specific rotatory power of this solution, viz. 38, it follows that it contains some 5*5 per cent of pseudo-compound for 94*5 of the normal. XThe change in rotation of an optically active solution is usually known as mutarotation (p. 309), and is a property exhibited by various optically active compounds, especially sugars, e.g. glucose, galactose, xylose, milk-sugar, and maltose, and certain hydroxy-acids and their lactones, e.g. anhydrous lactic acid. In all cases the rotation changes when the solution is kept; with glucose, for example, the value decreases to half, with milk-sugar the values are as 1'6:1, with galactose 1*46:1, and with xylose 4'67 : 1. The rotatory powers of maltose and lactic acid solutions increase when kept. All acids and alkalis appear to facilitate the conversion, and in the order of their degree of ionization. Common salt, alco- hol, and various organic compounds, on the other hand, tend to retard the transformation. Various theories have been brought forward in order to account for the phenomenon. The first of these assumed the presence of complex molecules, e.g. (C 6 H 12 6 ) X , in the freshly- prepared solution, and the gradual decomposition of these into the simpler molecules, C 6 H 12 6 , thus producing a lowering of the rotatory power. The assumption of the presence of com- plex molecules was rendered untenable as soon as it was shown that the molecular weight, as determined by the cryoscopic method, is the same in the freshly - prepared and the old solution. The second explanation was that, after solution, water is either withdrawn from or added on to the original molecular aggregates. The latest theory is that the different MUTAROTATION 659 rotations are due to different isomeric substances present in the two solutions, and that a gradual change in rotation accompanies the conversion of the one isomeride into the other. Tanret (1895) claimed to have isolated three distinct modi- fications of (/-glucose, which had the respective specific rotatory powers a = +105, j3 = -f-52'5, and 7 = +22-5. More recent work (E. F. Armstrong, J. C. S. 1903, 1305; 1904, 1043) indicates that in the case of (/-glucose only two distinct iso- merides actually exist in solution, viz. the a and 7, and that the so-called /^-modification is merely a mixture of the a and 7 in chemical equilibrium. The a- and 7-modifications are represented as stereo -isomeric, and correspond in structure with the a- and /3-methyl-glucosides (p. 310), since these glu- cosides, when hydrolysed with enzymes, have rotatory powers of the order of those of the a- and 7-glucoses, and the addition of an alkali to the products of hydrolysis produces the same change as with the a- and 7-sugars. They are therefore now termed a- and /^-glucoses, and may be represented by the configurations : OH.CH 2 .CH(OH).CH.CH(OH).CH(OH).C<o H (a) and OH.CH 2 .CH(OH).CH.CH(OH).CH(OH).C<2 H O 8 ) (Compare also Behrend and Both, A. 1904, 331, 359, and Lowry, J. C. S. 1904, 1551). Lowry concludes that in an ordinary solution of glucose, in addition to the a- and /?- modifications, small amounts of the aldehyde or aldehyde- hydrate are also present. This accounts for the aldehydic properties of glucose solutions, and also affords an explanation of the conversion of the a- into the /3-glucose: H-C-OH CH(OH) 2 OH-CH 'CH-OH CH-OH X^CH-OH XV H.OH ^ CH.OH X CH.OH CH CH-OH CH CH-OH CH-OH CH-OH CH 2 -OH CH 2 -OH CH 2 -OH a-Glucose Aldehyde-hydrate p-Glucoae. (For rwimt, see Lowry, B. A. Kep. 1904, 193.) 660 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION Asymmetric Synthesis. It has already been stated that the product formed by the synthesis of a compound containing an asymmetric carbon atom from symmetrical compounds is al- ways a mixture or compound of the d- and /-modifications in equal amounts, and a single active modification can only be ob- tained by the resolution of this r^cemic compound or mixture. Numerous attempts have been made to carry out an asym- metric synthesis, i.e. according to Marckwald (B. 1904, 37, 1368), to obtain artificially an optically active compound from a sym- metrical substance by the employment of an active product but without the use of an analytical process (such, for example, as those involved in the usual separation of racemic mixtures). A synthesis suggested by E. Fischer was as follows: By the cyanhydrin reaction mentioned on p. 304 it is possible to trans- form an optically active monose containing C n into a mixture of two active sugars containing C n+1 . The amounts of the two active compounds vary considerably in different cases, and with d-mannose only one c/-mannoheptose can be isolated. Similarly the d-mannoheptose yields only one mannooctose, and this only one nonose. If it were possible by some method to de- compose this d-manno-nonose so as to regenerate ctanannose then the other product would be an active glyceric aldehyde : Mannononose, CHO CH(OH) CH(OH)4-CH(OH) [CH OH] 4 CH 2 OH -* glyceric aldehyde, CHO.CH(OH).CH 2 .OH and CHO.LCH.OHJ4.CH2.0H. Cohen and Whiteley (J. C. S. 1901, 1305), starting with cm namic acid, prepared active amyl and menthyl esters, to which they added bromine and then attempted to obtain an active cinnamic acid dibromide, CgH^ CHBr - CHBr C0 2 H, by the hydrolysis of the esters, but without success. The hydrolysis of the products obtained by reducing the active amyl and menthyl esters of mesaconic, a-methylcinnamic, and pyruvic acids gave rise to inactive acids. Similar negative results were obtained by Kipping (P. 1900, 226). A. M'Kenzie (J. C. S. 1904, 1250; 1905, 1373; 1906, 365) has succeeded in accom- plishing several asymmetric syntheses. Thus when /-menthyl ( pyruvate, CH 3 CO CO OC 10 H 19 , is reduced by aluminium amalgam, a mixture of unequal amounts of /-menthyl d-lactate and /-menthyl /-lactate is formed. When this mixture is hy- drolysed by an excess of alcoholic potassic hydroxide and the /-menthol removed, a dextro-rotatory potassic salt containing THE WALDKN INVERSION 661 an excess of Mactate over d-lactate is produced ; this mixture, when acidified, becomes laevo-rotatory, and the asymmetric synthesis of /-lactic acid is thus accomplished. If tmenthyl benzoylformate, C 6 H 5 CO C0 2 C 10 H 19 , is treated in exactly the same manner, the final product is r-mandelic acid, due, probably, to the racemizing effect of the alkali. A second asymmetric synthesis has been accomplished by M'Kenzie by means of Grignard's reaction. Thus Z-menthyl benzoylformate and magnesium methyl iodide yield the additive compound CMePh(O.MgI)(C0 2 C lp H ]9 ), which is converted by dilute acids into the Z-menthyl phenylmethylglycollate CMePh(OH) (C0 2 C ]0 H 19 ), from which, on hydrolysis with alcoholic potas- sium hydroxide, a laevo-rotatory potassium phenylmethylgly- collate, CMePh(OH)(C0 2 K), was obtained. Thus C 6 H 5 .CO-C0 2 H -* CeH 5 .CO.COAoH 19 C 6 H 6 .C(CH 8 )(OH)(C0 2 C 1 oH 19 ) Inactive Active Active -* C 6 H 5 .C(CH 3 )(OH)(C0 2 H) Active. Similar active acids have been obtained by using other Ghignard reagents in conjunction with /-menthyl benzoylformate. For a further asymmetric synthesis, see Marckwald, B. 1904, 37, 349. The Walden Inversion. In a chemical reaction in which one radical is displaced by another, it is usually assumed that the group introduced takes the place of the radical removed, unless reasons to the contrary can be adduced. When an optically active compound is used we should expect the pro- duct formed to correspond in configuration with the original substance That this is not always true follows from the fact that during certain reactions racemization occurs, and the pro- duct obtained is optically inactive (cf. p. 257). Even more remarkable than this is the phenomenon known as Walden's inversion. An example of this is met with in the conversion of J-chloro-succinic acid into the d-isomeride by the following series of reactions : J-Chloro-acid * -malic acid * c?-chloro-acid. Moist Ag 2 PC1 5 It is not possible to say which of the two reactions is normal and which abnormal, as although the malic acid may be laevo- rotatory, its configuration may correspond with that of the d-chloro-acid and not with that of the /-acid. (B. 32, 1833) carried out a remarkable series of 662 XLVII. PHYSICAL PROPERTIES AND CONSTITUtiOtf experiments on the reaction between /-chloro- and /-bromo- succinic acids and various alkalis. He found that the hydrox- ides of potassium, rubidium, and ammonium gave practically pure c/-malic acid, moist silver oxide gave the pure /-malic acid; and the hydroxides of sodium, barium, lead, and lithium gave mixtures in which the d-acid preponderated, whereas oxides of mercury and palladium gave mixtures in which the /-acid was in excess. The conclusion was drawn that the reaction with potassium hydroxide is normal, and that inver- sion occurs when silver oxide is used. Interesting cases are those in which a complete cycle is involved, e.g.: 1. /-Chloro-succinic acid * /-malic acid I ifototAoO , 7 I * Moist Ag 2 * a-mahc acid * a-chloro-succmic acid. 2. d- Alanine * /-bromo-propionic acid t NH NOBr I NH c?-bromo-propiomc acid * /-alanine. 3. d-C 6 H 5 .CH(OH).C0 2 H *- /-C 6 H 6 .CH(NH 2 ).C0 2 H I T> HN 2 t xrrr /-C 6 K 6 .CHC1.C0 2 H d-C 6 H 5 .CHCl-CO 2 H . CH(NH 2 ) C0 2 H In some of these cases it is possible to determine in which of the different reactions inversion occurs; thus in Example No. 2 the reaction with nitrosyl bromide is abnormal and not that with ammonia, as E. Fischer has shown that under very varying conditions ammonia always gives the same product. With NOBr c?-alanine gives /-bromo acid, but the ester of r/-alanine reacts with NOBr, giving d-bromo-propionic acid. /-Valin (amino-isovaleric acid), with NOBr gives the /-bromo acid, and this with ammonia yields /-valin. Practically all the inversions mentioned above occur wiien the asymmetric carbon atom has a carboxyl group attached to it. Experiments made by E. Fischer and Scheibler, with compounds in which the asymmetric atom is in the /3-position with respect to the carboxylic group, prove that inversion does not take place: PC1-, -CH a .CH(OH).CH 2 .C0 2 H =r d-CH 3 .CH(OH).CH 2 .C0 2 II, AftO WALDEN INVERSION 663 and similar results are obtained when the methyl esters are used. The same holds good in the case of /3-hydroxy-/?-phenyl- propionic acid (M'Kenzie and Humphreys). There are, how- ever, several exceptions, e.g. : 1. Fischer: c?-/3-Amino-butyric acid * Z-/3-hydroxy-butyric acid NOCI -j8-chloro-butyric acid c?-/3-hydroxy-butyric acid. Water 2. M'Kemie and Barrow: c?-/3-Hydroxy-)S-phenyl-propionic acid * c?-j8-chloro-/3-phenyl-propionic acid 80C1 * J Water J-j3-hydroxy-j8-phenyl-propionic acid. Frequently phosphorus pentachloride and thionyl chloride react differently, e.g.: PC1 5 -Mandelic acid or ester * c?-chloro acid or ester Z-mandelic acid or ester * Z-chloro acid or ester. SOC1 2 In connection with this the following cycles are of interest. Z-Mandelic acid * d-chloro acid f NaOH rcl J NaOH Z-chloro acid * c?-mandelic acid PC1 6 MVIandelic acid ^-chloro acid J Ag 2 C0 3 + water SOCI 2 J Ag 2 C0 3 + water c?-chloro acid * c?-mandelic acid. SOC1 2 of ^8-hydroxy-^-phenyl-propionic acid it has been the reaction with thionyl chloride is normal, since In the case shown that the the chloro ester derived from the Z-hydroxy ester is trans- formed back into Z-hydroxy acid when warmed with water and marble. (For details see Walden, B. 28, 2772; 29, 133; 30, 3146 E. Fischer and students, B. 41, 889, 2891; 42, 1219; 43, 2020; A. 381, 123; 383, 337; 386, 374. Werner, A. 386, 65. M l Kenzie and others, J. C. S. 1908, 811; 1909, 777; 1910, 121, 1016, 1355, 2564; 1911, 1910, 1912, 390. Bulmann, A. 1912, 388, 330.) 664 XLVII. PHYSICAL PROPERTIES AND CONSTITUTION I. Electrical Conductivity. Attention has previously (p, 161) been drawn to the fact that the degree of ionization, a, of an acid in solutions of given concentration, v, may be deter- mined by a comparison of the electrical conductivity, X (re- ciprocal of resistance), at that dilution with the conductivity at infinite dilution when ionization would be complete, i.e. a = . From Ostwald's dilution law, based on the law of aoc 2 mass action, it follows that - is a constant = &, where v(l - a) v = number of litres of solution containing one equivalent of acid. This constant k (or 100& = K) is known as the dis- sociation constant, and is used as a measure of the strength of all feeble acids. The effect of the introduction of strongly negative groups into the acid molecule on this constant has been referred to (pp. 168, 447), and the influence of strongly positive groups, e.g. NH 2 , is equally marked. Thus benzoic acid == 0*006, 0-amino-benzoic = 0*0009, m-amino-benzoic = O'OOIO, and jp-amino-benzoic = O'OOS. Hantzsch has used the electrical conductivity method in the diagnosis of pseudo-acids and bases. Thus with certain nitro- compounds the ordinary compound R-CH 2 N0 2 is a pseudo- acid and the isonitro-compound RCH:NOOH is a true acid, and all the salts are derived from the latter. These salts, as a rule, are but little hydrolysed, as the isonitro-compounds are relatively strong acids. A solution of such a salt will thus contain the metallic ions and the isonitro-ion KCH:NO0. When this solution is mixed with an equivalent quantity of hydrochloric acid the ions present are Na, Cl, E-CH:NO0', + and H. In the majority of cases there is a considerable ten- dency for the strongly acidic and hence strongly ionized isonitro-compound (true acid) to become transformed into the ordinary nitro-compound (pseudo-acid). As this is practically a non-electrolyte, it follows that as this transformation occurs the conductivity of the solution will gradually diminish until it attains the value of a sodium chloride solution of the given concentration. Thus with sodium ^-bromophenylnitromethane, C 6 H 4 Br.CH:NO.ONa, at 25, and 0= 256, after mixing with an equivalent of hydrochloric acid, the conductivity, /* = 151 '4 after 1-5 minute, and after 45 minutes a constant value p = 129-5 was obtained. This approximates to the value /^ = 114'4 ELECTRICAL CONDUCTIVITY 665 for sodic chloride, and the difference may be due to secondary changes. Similar results have been obtained with pseudo-bases. The true base, methyl-phenyl-acridonium hydroxide (I), which is first liberated when salts of the base are decomposed with alkali, is readily transformed into the pseudo-base with the carbinol formula (II): II which is practically a non-electrolyte. When a solution of the chloride of the base is neutralized with an equivalent of sodic hydroxide, the solution has a maximum conductivity which gradually diminishes until the value for a solution of sodic chloride of the given concentration is practically reached. Similarly with the sulphate and an equivalent quantity of barium hydroxide; at and v = 256, the initial conductivity was /*= 119'2, but after 15 hours it had fallen to ft = 1-7 (due to small amounts of dissolved baric sulphate). Phenomena of this kind, which are termed by Hantzsch "slow neutrali- zation ", are largely used to denote tautomeric change, i.e. the change from a true acid to a pseudo-acid or from a true base to a pseudo-base (cf. p. 485) during the conversion of the salt into the acid or base. The study of other physical properties such as Internal Viscosity (Zeit. phys. 1887, 1, 285, 293; 1888, 2, 744; com- pare also Dunstan, J. C. S. 1907, 1728; 1908, 1815, 1919; 1909, 1556; 1910, 1935), Heat of Combustion (Stohmann, Zeit. phys. 1890, 6, 334; 1892, 10, 410), Capillary Constants (Schiff, A. 1884, 223, 47), Magnetic Susceptibility (Pascal, Bull. 1909, 1110; 1910, 17, 45; 1911, 6, 79, 134, 177, 336, 809. 868) indicate that here also there are similar relation- ships between constitution and physical properties. 666 XLVIIL FERMENTATION AND ENZYME ACTiOJi XLVIII. FERMENTATION AND ENZYME ACTION A. Alcoholic Fermentation. Lavoisier, 1789, was the first to recognize that alcoholic fermentation consists essentially in the ^decomposition of a sugar into alcohol and carbon dioxide; and Gay-Lussac, 1810, drew attention to the fact that the presence of air appeared to be essential for fermentation and putrefaction to take place. The fact that brewers' yeast is a low form of plant life was discovered independently by Cagnaird-Latour, Theodor Schwann, and Kutzing, 1837. By microscopical examination they observed the growth of the organism, and showed that it could be destroyed by heat or by certain poisons. These results were not accepted by Berzelius, Liebig, and others, who still regarded yeast as a chemical substance without life. According to Berzelius the yeast acted as a contact substance which decomposes the sugar without undergoing change itself; whereas Liebig re- garded the ferment as an extremely susceptible substance, which undergoes a change of the nature of decay, and sug- gested that the decomposition of the sugar was a type of sympathetic reaction induced by the change of the ferment. In 1857 Pasteur began his researches on fermentations. He was able to show that in other cases of fermentation, such as the lactic fermentation of milk, micro-organisms are present. He was further able to show that during alcoholic fermenta- tion the yeast grows and multiplies, and was led to the conclusion that fermentation is a physiological process ac- companying the life of the yeast. In his own words: "I am of opinion that alcoholic fer- mentation never occurs without simultaneous organization, development, multiplication of cells, or the continued life of cells already formed". This conclusion harmonized with the facts already known that boiled liquids could be kept from fermenting by heating or filtering through cotton wool the air admitted to the liquid. It was Pasteur who proved that only 95 per cent of the glu- cose is accounted for as carbon dioxide arid alcohol ; he was able to isolate glycerol and succinic acid from the final products. As early as 1858 M. Traube expressed the view that all fermentations produced by living organisms are ultimately due to ferments, which are definite chemical substances manu- factured in the cells of the organism. These ferments he re- ALCOHOLIC FERMENTATION 667 garded as analogous to proteins. Traube's conclusions have been verified in the case of alcoholic fermentation by Buchner's isolation of " zymase " from yeast (see p. 77). Buchner's yeast juice, when quite free from yeast cells, can ferment solutions of glucose, fructose, sucrose, and maltose; and the fermenting power is not destroyed by the addition of chloroform, benzene, or sodium arsenite, antiseptics which inhibit the action of living cells, by filtration through a Berkefeld filter, by eva- poration to dryness at 30-35, or by precipitation with alcohol. The fermenting power is, however, completely de- stroyed by heating to 50, or by the addition of powerful anti- septics. The activity of the juice diminishes in the course of time, as a digestive enzyme is also present which gradually decomposes the zymase. Both in rate of fermentation and in the total fermentation produced, the extract or juice is much less efficient than the equivalent amount of living yeast, and g'ycerol is formed as a by-product when the extract is used, uring fermentation a portion of the sugar is converted into a compound of less reducing power which is not fermented, but which yields sugar when hydrolysed with acids. Per- manent preparations containing zymase can be obtained by evaporating the juice to a syrup at 20-25, drying at 35, and then exposing to sulphuric acid in a vacuum desiccator. Such a powder when dry retains its activity for twelve months, and can be heated at 85 for eight hours without any serious loss of fermenting power. Another preparation can be obtained by bringing the juice into 10 volumes of acetone, centrifuging, washing the precipitate with acetone and then with ether, and drying over sulphuric acid. An important medicinal preparation known as zymin is manufactured by stirring moist yeast with acetone, filtering and draining at the pump, again mixing with acetone and draining. The product is then roughly powdered, kneaded with ether, filtered, drained, and spread on filter paper or porous plates, and finally dried at 45 for twenty-four hours. This product is quite incapable of growth or reproduction, but produces fermentation and is much more active than yeast extract. The researches of Harden and Young (Abs. 1905, ii. 109; 1906, i. 470) indicate that the activity of yeast juice or ex- tract is due to an enzyme and a co-enzyme, which can be separated by filtration or dialysis through a Martin gelatin filter; the residue contains the enzyme, and the filtrate or dialysate the co-enzyme. Neither by itself can induce fer- 668 XLVIII. FERMENTATION AND ENZYME ACTION mentation, but a mixture of the two is equal in activity to the original juice. The co-enzyme is dialysable, and is not destroyed by boiling, but disappears from yeast juice during fermentation, or when the juice is allowed to undergo auto- lysis. It cannot be a protein, and its nature has not yet been determined. It is decomposed by acid or alkaline hydrolysing agents, by repeatedly boiling the extract, and also by the lipase of castor-oil seeds. In the case of other fermentations brought about by enzymes, e.g. lipase, it has been clearly demonstrated that both enzyme and co-enzyme are necessary, and also that the co-enzyme is a metallic salt of the com- plex taurochloric acid (p. 196). Harden and Young (Abs. 1908, i. 590) have also shown that phosphates added to a mixture of glucose and yeast juice produce both an initial acceleration and also an increased total fermentation. An optimum concentration of phosphate exists which produces a maximum initial rate of fermentation; an increase beyond this optimum diminishes the rate. The reaction between the glu- cose and phosphate is represented by the following equations : 2C 6 H 12 6 + 2Na 2 HP0 4 = 2C0 2 + 2C 2 H 6 + C 6 H 10 4 (P0 4 Na 2 ) 2 + 2H 2 and C 6 H 10 O 4 (P0 4 Na 2 ) 2 -f 2H 2 O = C 6 H 12 O 6 According to the second of these, the glucose phosphate is hydrolysed by the water and yields sodium phosphate, which can then react with a further quantity of glucose. These conclusions are supported by the following facts. Careful experiments have shown that during the period of increased fermentation the amounts of alcohol and carbon dioxide pro- duced exceed those which would have been formed in the absence of added phosphate by a quantity exactly equivalent to the phosphate added in the ratio C 2 H 6 : Na 2 HP0 4 . (Com- pare also Iwanoff, Abs. 1909, 1, 752.) It has been proved that the metallic phosphate is not the co-enzyme already mentioned, as the filtered enzyme and phosphate are not capable of induc- ing fermentation in the absence of the filtrate. Fermentation does not proceed in the absence of phosphate although both enzyme and co-enzyme are present, and although arsenates and arsenites have accelerating actions on the rate of fer- mentation they cannot be used in place of the phosphate. The function of the arsenate or arsenite appears to be to act as accelerators in the decomposition of the glucose phosphate. Slator finds that phosphates have not an accelerating effect ALCOHOLIC FERMENTATION 669 when living yeast cells are employed. He has estimated (J. C. S. 1906, 89, 128; 1908, 93, 217) the amounts of car- bon dioxide evolved during given periods of time when yeast itself is used, and finds that the rate of fermentation is exactly proportional to the amounts of yeast present, and is almost independent of the concentration of the glucose. A yeast which can ferment glucose does not necessarily ferment iso- meric sugar, e.g. galactose; it is probable that different enzymes are required for the different sugars. The fermentation of glucose undoubtedly consists of a whole series of chemical reactions; at present we know the sub- stances we start with and the final products obtained. Several suggestions have been made with regard to the nature of some of the intermediate products. Buchner and Meisenheimer (B. 1905, 38, 620) have suggested that lactic acid (p. 213) is first formed by the action of zymase on glucose, and that a second enzyme, lactacidase, then decomposes the lactic acid into ethyl alcohol and carbon dioxide. A serious objection to this view is that lactic acid itself is only very slowly fermented by yeast (Slator). Another suggestion is that dihydroxy-acetone, CO(CH 2 OH) 2 , is an intermediate product, and it has been proved that this compound can be fermented by yeast (Buchner and Meisen- heimer, B. 43, 1773; Lebedew, 44, 2932); compare also Fmnzen and Steppuhn, ibid., 2915. Of the by-products mentioned on p. 76, glycerol is formed from the sugar, as Buchner and Meisenheimer have shown that it is also formed when yeast extract or zymin acts on sugar solutions. The fusel oil and succinic acid, on the other hand, do not owe their origin to the sugar, but to other products present in the mixture undergoing alcoholic fermentation. The researches of F. Ehrlich (1904-1910) prove that the alcohols and also the aldehydes present in ordinary fusel oil are derived from the amino-acids formed by the hydrolysis of proteins. Thus isoamyl alcohol, one of the chief consti- tuents of fusel oil, is closely related to leucine, a-amino isohexoic acid, and active amyl alcohol to isoleucine, a-amino- /J-methyl-valeric acid, both of which are formed by the hy- drolysis of proteins, and according to Ehrlich both these acids are transformed into the corresponding amyl alcohols under the influence of pure yeast cultures, in the presence of sugar: HO 670 XLVIII. FERMENTATION AND ENZYME ACTION These changes, although brought about by yeast, do not occur when zymin or yeast extract is used. Other amino acids undergo a similar decomposition : tyrosine (p. 459) yields 2?-hydroxy-phenyl-ethyl-alcohol, tyrosol, OH C 6 H 4 CH 2 CH 2 OH, and phenyl-alanine (p. 453) gives phenyl-ethyl alcohol. The ammonia is not found at the end of the reaction, as it is used up by the organism for the purpose of building up new protein molecules. If appreciable amounts of simple nitrogenous substances, such as ammonium salts, are originally present in the fermenting liquor, the organism uses these in preference to decomposing the amino-acids; and Ehrlich has found it possible to increase or diminish the amounts of fusel oil formed, by diminishing or increasing the amounts of am- monium salts present at the beginning of the fermentation. Practically all amino-acids formed by the hydrolysis of pro- teins can undergo similar decomposition by yeast, but only in the presence of sugar. The succinic acid found as a by- product in alcoholic fermentation is probably formed in a similar manner from glutamic acid. According to Neuberg and Fromherz (1911), ketonic acids are probably formed as intermediate products in the fermen- tation of amino-acids to alcohols; and Neuberg has been able to show that many a-ketonic acids, e.g. pyruvic, CH 3 -COC0 2 H, and oxalacetic, C0 2 H CH 2 CO C0 2 H, are readily decom- posed by yeast even in the absence of sugar, yielding carbon dioxide and aldehyde : CH 3 .CO.C0 2 H C With a 1-per-cent solution of pyruvic acid the decomposition is almost as rapid as with a sugar solution. The decomposi- tion is probably due to an enzyme, termed " carboxylase " by Neuberg. For fermentations induced by organisms other than yeasts, see pp. 150, 152, 214. According to Harden (J. C. S. 1901, 610), Badllus coli communis ferments glucose, fructose, or mannitol, yielding lactic, succinic, and acetic acids, alcohol, formic acid, carbon dioxide, and hydrogen. The main re- action can be represented by the equation: 2C 6 H 12 6 + H 2 = 2C3Hs0 3 + C 2 H 4 O 2 + C 2 H 6 + 2C0 2 + 2H 2 . With glucose the weight of lactic acid is practically 50 per cent of the sugar, and the alcohol and acetic acid are formed in equal amounts. The alcohol probably comes from the ENZYME ACTION 671 group CH 2 (OH) CH(OH), and as this group occurs twice in the molecule of mannitol the yield of alcohol is much greater when this compound is used. The lactic acid is probably derived from the CH (OH) . CH (OH) . CH(OH) grouping. B. typhosus yields similar products, except that it gives formic acid instead of carbon dioxide and hydrogen (Abs. 1906, II, 380). B. Enzyme Action. Attention has been drawn several times (pp. 76, 77, 423) to the fact that chemical decomposi- tions can be brought about by certain complex organic sub- stances found in animal and plant tissues. Such substances are termed unorganized ferments or enzymes. The great ma- jority act as catalysts in processes of hydrolyses, e.g. invertase which hydrolyses cane sugar, amylase which hydrolyses starch, emulsin (p. 423), myrosin (p. 593), pepsin and trypsin (p. 598), lipases which hydrolyse esters; but in addition there are enzymes which bring about oxidation, viz. the oxidases, enzymes which bring about complex reactions, e.g. zymases. The enzymes are unstable nitrogenous compounds of colloidal nature, but not necessarily proteins. They act as catalysts, in the majority of cases as positive, but in a few as negative. The catalytic nature is shown by the fact that the rate of reaction is directly proportional to the concentration of the enzyme, but that the total decomposition is independent of the amount of enzyme, provided sufficient time is allowed, and provided the enzyme does not undergo decomposition. They are sensitive to high temperatures, e.g. when heated to below 100 their activity is completely destroyed; they are, how- ever, resistant towards certain antiseptics which destroy pro- toplasm and kill fermenting organisms. Strong antiseptics, such as formaldehyde, tend to destroy enzymes. Enzymes are often precipitated from their colloidal solutions by the addition of alcohol or acetone, but such products are not pure; in many cases they consist of a mixture of enzymes, and in this way the study of their reactions is complicated. The modern system of nomenclature is to name the enzymes ac- cording to the compounds they hydrolyse, e.g. maltase, sucrase ( = invertase), amylase ( = diastase), &c.^ The nature of the products formed varies not merely with the substance used, but also with the enzyme; thus the trisaccharose, raffi- nose, if hydrolysed by acids, yields galactose, fructose, and glucose; the same carbohydrate with diastase yields melibiose and fructose, and with emulsin galactose and sucrose. The 672 XLVIIL FERMENTATION AND ENZYME ACTION action of enzymes is essentially selective, and in this respect differs from the hydrolysing action of alkalis or acids. Thus esters, amides, carbohydrates, glucosides, &c., are all hydro- lysed by hydrochloric acid; whereas esters, but not carbo- hydrates, can be hydrolysed by lipases, and maltose, but not sucrose, can be hydrolysed by maltase. Even a slight differ- ence in the configuration of two isomeric substances is suf- ficient to affect their reactivity with a particular enzyme, e.g. the two methyl-glucosides (p. 659), which are represented by the spatial formulae: C-OCHg H.C-OH\ HO.C.H HO.C.H H-C-OH H-C-OH CH 2 -OH CH 2 -OH, the only difference being the arrangement of the H and OCH 3 attached to the upper carbon atom. Of these two compounds the a can be hydrolysed by maltase but not by emulsin, and the ft by emulsin but not by maltase, and hence the names a and p glucase are sometimes used for the two enzymes maltase and emulsin. Numerous other examples of the same type have been met with, especially in the case of polypeptides (Fischer and Bergell, B. 36, 2592; 37, 3103). As most of the natural glucosides are hydrolysed by emulsin but not by mal- tase, they are regarded as analogous to the /3-methyl-glucoside, with complex radicals in place of the methyl group. Maltose on the other hand is an a-glucoside resembling the a-methyl compound in configuration. It has been proved in many cases that a particular enzyme can act not merely as a hydrolysing but also as a synthesizing agent. The process of hydrolysis is frequently a balanced reaction, although in the majority of cases the equilibrium is mainly in the direction of analysis and not synthesis. The synthesizing activity of an enzyme was first demonstrated by Croft-Hill (J. C. S. 1898, 634; 1903, 578) in the case of maltase. The greater portion of the maltose is hydrolysed to glucose, but a certain proportion of disaccharose is always present, and ENZYME ACTION 673 in a solution of glucose maltase can produce a certain amount of a disaccharose, which at first was thought to be maltose, but has since been proved (E. F. Armstrong, 1905) to be a mixture of maltose and isomaltose. Invertase, lactase, emulsin, and lipases have all been shown to possess synthetical activity. The formation of starch in plant and glycogen in animal tissues is probably largely due to the activities of synthesizing enzymes; and Potterin has succeeded in synthesizing atriolein, one of the common constituents of natural fats, by means of a lipase. The rate of hydrolysis by means of enzymes has been studied by different authorities. The investigations of O'Sul- livan and Thompson (J. C. S. 1890, 834) and of Hudson (J. Am. C. S. 1908, 1160, 1564; 1909, 655) prove that the inversion of sucrose by invertase constant values for K can be obtained by using the ordinary equation for a unimolecular reaction, provided that the complications attending the mutarotation of the glucose and fructose (p. 658) are avoided by adding a small quantity of alkali before taking the polarimetric reading. The alkali stops the inversion, and at the same time rapidly brings about equilibrium between the a- and /3-glucoses and the a- and /3-fructoses, so that the normal rotatory power of invert sugar is given. Hudson's results clearly prove that the a-modifications of glucose and fructose are first formed. A view generally held with regard to the mechanism of enzyme reaction is that combination (absorption compounds) occurs between the enzyme and the substrate (the substance decomposed), and that it is this compound which reacts with water. The fact that a specific enzyme can hydrolyse only particular substrates is in harmony with this view, as it is known that chemical constitution plays an important part in absorption. In living tissues a number of complex substances are present which are capable of interfering with the action of an enzyme. These are termed anti-enzymes. Some are normally present in tissue, others appear to be formed when an enzyme is injected into the tissue. 674 XLIX. CATALYTIC ACTION XLIX. CATALYTIC ACTION OF FINELY -DIVIDED METALS AND METALLIC OXIDES Attention has already been drawn to the reduction of carbon compounds by hydrogen gas, using finely -divided metals or metallic oxides as catalysts (p. 610). Within recent years it has been shown that finely-divided solids can act as catalysts in various other reactions. Oxidations. One of the most interesting of these is the decomposition of primary alcohols into aldehydes and hydrogen when passed through a tube containing iron, zinc, brass, zinc oxide, ferric oxide, or stannic oxide. At 660 in the presence of zinc, ethyl alcohol gives an 80-per-cent yield of acetalde- hyde, other primary alcohols behave in a similar manner, and isopropyl alcohol gives an almost quantitative yield of acetone. The reactions Primary alcohol i aldehyde + H a Secondary alcohol ^i ketone -{- H 2 are reversible in the presence of the catalyst, as an aldehyde and hydrogen when heated in contact with zinc or iron yield an alcohol. When alcohols are heated with hydrogen under pressure, and in contact with zinc or iron, the final products consist mainly of hydrocarbons if the temperature is fairly high, e.g. isoamyl alcohol yields considerable amounts of pro- pane and methane. The formation of these latter is probably due to the following series of reactions : (CH 3 ) 2 CH.CH 2 .CH 2 .OH (CH 3 ) 2 CH.CH 2 .CHO + HJJ. (CH 3 ) 2 CH.CH 2 .CHO -* (CH^CH-CHg-f CO. (CH 3 ) 2 CH.CH 3 + H 2 > CH 3 .CH 2 .CH 3 -f CH 4 . Reduced benzene derivatives can be oxidized to benzene compounds, but pentamethylene derivatives are not oxidized. Zelinsky shows (B. 44, 3121) that palladium black can also bring about oxidations at about 200-300 e.g. hexamethy- lene benzene (ibid. p. 2302) and gives an example, viz. : methyl-tetrahydro-terephthalate, which is both oxidized and reduced by hydrogen in the presence of palladium black. Dehydration. When alcohols are heated at 400-500 in the presence of aluminic oxide (A1 2 8 ) a decomposition into olefine and water occurs, no aldehyde being formed. This appears to be a simple method for obtaining an olefine from DEHYDRATION 675 the corresponding alcohol. It has been shown that the alu- minic oxide loses its activity when strongly heated and rendered insoluble in acids or alkalis. Later experiments have shown that when the alcohols are heated under pressure with the oxide, the primary decomposition is into water and an ether, and that at higher temperatures the ether yields an olefine and water: 2CH 3 .CH 2 .OH (CH 3 -CH 2 ) 2 O + H 2 O (400) (CH 3 .CH 2 ) 2 - 2CH 2 :CH 2 -fH 2 (530). This reaction is characteristic of primary and secondary alco- hols, and does not occur in the absence of the catalyst, even when higher temperatures are used. The first reaction is reversible, as ether, under similar conditions, yields a certain amount of alcohol. Unsaturated hydrocarbons can also be obtained by the action of aluminic oxide on cyclic alcohols; thus menthol (p. 578) yields menthene. The same catalyst at 200-300 is able to transform ethylene oxide and its homologues into the isomeric aldehydes : - CH 3 .CH:a A similar change occurs in the absence of the catalyst, but at a higher temperature, viz. 500-600. Bouveault (Bull. Soc. Chim. 1908 [4], 3, 119) finds that good yields of aldehydes can be obtained by passing primary alcohols over copper coils heated by an electric current. Secondary alcohols under similar conditions ' yield ketones and hydrogen, and ketonic alcohols, E.CH(OH).CO-E, yield kiketones, E-CO-CO-E, and hydrogen. Unsaturated alcohols undergo molecular transformation and yield saturated aldehydes : Numerous other substances, e.g. pumice, animal charcoal, sand, red phosphorus, and aluminic phosphate, can decompose alco- hols into olefines and water, but oxide of aluminium appears to be the best (Senderens, C. E. 1907, 144, 381, 1109). ^ Bou- veault has designed a special apparatus for the preparation of olefines by this method. The action of silica as a catalytic agent is extremely char- acteristic. Pure precipitated silica, moderately calcined, decom- 676 XLIX. CATALYTIC ACTION poses ethyl alcohol at 280, yielding pure ethylene. After it has been more strongly calcined, it induces decomposition only at a higher temperature, and then yields ethylene and water together with hydrogen and aldehyde. Pulverized quartz can yield as much as 50 per cent of the theoretical amount of hydrogen and 50 per cent of ethylene. Similarly, alumina which has been strongly calcined decomposes part of the alcohol into hydrogen and aldehyde. Experiments made with gypsum (CaS0 4 , 2H 2 0) dehydrated below 400 and with an- hydrite (CaS0 4 ) indicate that the catalytic dehydration of alcohols is effected by substances which are capable of forming temporary hydrates. Thoroughly calcined gypsum or natural anhydrite decomposes alcohol at high temperatures only, and then yields mainly hydrogen and acetaldehyde; on the other hand, gypsum which has been dehydrated at a moderate tem- perature is capable of combining with water, and decomposes alcohol at about 400, yielding ethylene (Senderens, Bull. Soc. Chim. 1908 [41, 3, 197, 633). Sabatier and Maihle (Annales, 1910 [viii], 20, 289) have studied the action of the following metallic oxides on primary alcohols, more especially ethanol: Th0 2 , A1 2 3 , Cr 2 3 , Si0 2 , Ti0 2 , BeO, Zr0 2 , U0 2 , Mo 2 5 , Fe.O^ V 2 3 , ZnO, MnO, CdO, Mn 3 4 , MgO. The first four act almost entirely as dehy- drating agents, and at 340-350 give 90-100 per cent yields of olefine and little or no hydrogen. On the other hand, the last five oxides bring about oxidations, and give practically 100 per cent of hydrogen and no olefine. BeO and Zr0 2 give approximately equal volumes of hydrogen and olefine, i.e. they are mixed catalysers, as are practically all the intermediate oxides. According to these chemists the activity of finely- divided metals or oxides is due to the formation of unstable additive compounds; e.g. in catalytic oxidations of \mstable hydrides : Alcohol 4- metal * metallic hydride + aldehyde Metallic hydride * metal -f- hydrogen, such hydrides are readily decomposed, and yield the metal which can react with a further quantity of alcohol. With the readily reducible metals, SnO, CdO, &c., a small amount of metal is formed, and this reacts as above. As the activity does not increase with time, as might be expected as more oxide becomes reduced, it is suggested that the metal gradu- ally becomes less finely divided and hence less active. Oxides FORMATION OF AMINES 677 which are not readily reduced may form unstable compounds with hydrogen or with the aldehyde. The mechanism of catalytic dehydration does not consist in the formation of unstable hydrates of the catalyst as at first supposed, but in the formation of alkyl salts, formed by the union of the alcohol with the acidic oxide used as catalyst: ThO 2 + 2EtOH -* ThO(OEt) 2 + H 2 O ThO(OEt) 2 -> 2C 2 H 4 -f ThO(OH) 2 ThO(OH) 2 Th0 2 + H 2 0. Esterification. Sdbatier and Maihle (C. E. 1911, 152, 494) have shown that Ti0 2 is a good catalyst for the conversion of acids and alcohols into esters. The method is to allow a mix- ture of molecular proportions of the vapour of the two com- pounds to pass over a column of the diDxide kept at 290-300. The yield of ester is about 70 per cent, and the process is extremely rapid. A similar method may be used for hydro- lysing esters, e.g. allowing a mixture of the ester vapour with an excess of steam to pass over the dioxide at 280 -300. Similar results are obtained with thorium oxide, provided aromatic acids are used. Formation of Amines, Thiols, Ketones. Amines are formed when a mixture of an alcohol and ammonia is passed over thorium dioxide at 350-370 (C. E. 1909, 148, 898); thiols (mercaptans) are formed when a mixture of alcohol and hy- drogen sulphide is passed over the dioxide at 300-360 (C. E. 1910, 150, 1217, 1569). The yields are especially good with primary alcohols, and even phenol gives a 17-per-cent yield of thiophenol at 430-480; and metallic sulphides, especially CdS, at 320-330, decompose thiols into alkyl sulphides and hydrogen sulphide. Ketones can be prepared by the action of acid anhydrides or acids on thorium dioxide at 400 (Senderens, C. E. 1909, 149, 213, 995; 1910, 150, 111, 702, 1136). Simple and mixed aliphatic ketones and mixed aromatic aliphatic ketones have been prepared, the mixed ketones by using mix- tures of two acids. Aromatic acids containing the carboxylic group attached to the benzene nucleus do not react unless mixed with an aliphatic acid, but acids of the type of phenyl- acetic do. The reaction probably consists in the formation of a salt and its subsequent decomposition into ketone, cap bon dioxide, and water. Formic acid behaves somewhat differently from the other fatty acids (Sdbatier and Maihle, C. E. 1911, 152, 1212). Finely 67$ 1* tTNSATTTRATIOtf divided Pd, Pt, Ni, Cu, Cd, and ZnO or SnO decompose it into carbon dioxide and hydrogen. Ti(X and W 2 5 yield water and carbon monoxide, and Si0 2 , Zr0 2 , AlgOg, &c., give both reactions. L. UNSATURATION A. Types of Unsaturation. Unsaturated compounds are usually defined as those which are capable of uniting with another substance (element or compound) without disruption of their original structure. Two main types of such com- pounds have been dealt with in the previous chapters. I. Cases in which the addenda unite with two different atoms of the original compound. Such are the compounds supposed to contain double or triple linkings between C and C, C and 0, and S, C and N, N and N, as seen in the groups of olefine and acetylene derivatives, carbonyl com- pounds, thiocarbonyl derivatives, nitriles and Schiff's bases, azo-com pounds. II. Cases in which the addenda unite with one and the same atom of the original compound, as in the conversion of amines into salts and quaternary ammonium compounds, the formation of oxonium salts from ethers, &c., and the formation of sulphonium salts from alkyl sulphides. The presence of such unsaturated groups as amino and hydroxyl, and also the alkylated groups, -NHK, 'NK 2 , .OR, produce marked effects on* the properties of the compounds into which they are introduced. In the aromatic series they render the compounds much more reactive towards reducing, oxidizing, and substituting reagents (cf. p. 409). When fur- ther substituents are introduced, e.g. Cl, Br, S0 3 H, N0 2 , &c., these almost invariably take the ortho and para positions with respect to the unsaturated group. These groups also tend to make the compound luminesce under the influence of electric discharges under small pressures. They are also the most powerful auxochromes known; i.e. when introduced into a compound containing chromophores, such as, 'N:N, C:0, C:C, N0 2 , &c., they produce a deepening of the colour of the compound. In examples of the first type the question as to whether addition or not takes place depends upon a variety of factors. PROPERTIES OF UNSATURATED ACIDS 679 (1) Whether the double linking is between C and C, C and 0, C and N, or N and N. Thus although both olefines and carbonyl derivatives combine with hydrogen, the first group adds on bromine readily, whereas the second does not; and the second combines with hydrogen cyanide or sodium bi- sulphite more readily than the first group does. (2) The nature of the groups already attached to the two atoms which are united by the double linking. Thus although most olefine derivatives combine with bromine, compounds in which there are several negative groups, such as Ph, Br, CN, C0 2 H, already attached to the two carbon atoms, do not form addi- tive compounds with bromine (Hugo and Bauer, B. 37, 3317), although they contain an olefine linking. (3) The nature of the addenda. It has been pointed out already (p. 44) that chlorine combines most readily and iodine least readily, but that hydrogen iodide combines more readily than hydrogen chloride or bromide. (4) Conditions of the experiment, e.g. nature of solvent, sunlight, temperature, presence of a catalyst, &c. Phenyl-propiolic acid does not combine with hydrogen chloride when in aqueous solution below 80. B. Properties of TTnsaturated Acids as affected by the position of the Double Bond. Acids which contain a double bond in the a/3 position differ in many respects from isomeric acids in which this bond is further removed from the car- boxylic group. The (ip unsaturated acids are reduced much more readily than their isomerides by sodium amalgam and water. This is somewhat remarkable, since in the case of other additive reactions, for example, the addition of bromine, the aj3 un- saturated acids are less reactive, i.e. do not combine with bromine so readily as /3y unsaturated acids or other acids in which the double bond is far removed from the carboxyl group (Sudborvugh and Thomas, J. C. S. 1910, 715, 2450). The readiness with which aft unsaturated acids can be reduced may perhaps be accounted for by the presence of the con- jugated double bonds (cf. p. 681) R.CH:CH.C:6 + 2H R.CH 2 .CH:C.OH -* R.CH 2 .CH 2 .C:O OH OH OH 1:4 addition takes place, but the resulting unsaturated glycol is unstable and, by a wandering of an atom of hydrogen, yields the saturated acid. 680 L. UNSATURATION /. Bougault (C. E. 1905, i. 9) shows that /3y unsaturated acids combine with the elements of hypoiodous acid (HIO), yielding lactones, whereas the isomeric a/3 acids do not. This provides the basis of a method for separating a mixture of an a/3 and /3y unsaturated acid. One of the best methods of separating a mixture of a/3 and /3y unsaturated acids is due to Fittig (B. 1894, 27, 2667: A. 1894, 283, 51), and consists in heating the acids for a few minutes at 140 with a mixture of equal volumes of concen- trated sulphuric acid and water. The a/3 acid is unaffected by this treatment, whereas the /3y acid is converted into a y-lactone (p. 217) which is insoluble in sodium carbonate solution. (CH 3 ) 2 C:CH.CH 2 .CO.OH When this method is used only the a/3 acid can be re- covered. A method by means of which both acids can be recovered is the separation by fractional esterification, as an a/3 acid is esterified much less readily than isomeric unsatu- rated acids (Sudborough and Thomas, J. C. S. 1911, 2307). One of the best methods for determining the position of the double bond in the case of an olefine acid is by an examination of the oxidation products (p. 162). These consist, as a rule, of a mixture of a monobasic and a dibasic acid, as the carbon atoms between which the olefine bond functionated both yield carboxylic groups; e.g. K'CH:CH.CH 2 .C0 2 H gives K-C0 2 H and C0 2 H.CH 2 .C0 2 H. Cf. also Oleic acid, p. 165. Dimethylacrylic acid, (CH 3 ) 2 C : CH C0 2 H, when oxidized yields acetone, (CH 3 ) 2 CO, and oxalic acid or its oxidation product carbonic acid. The conversion into ozonides and the decomposition of these (p. 624) is also used for the determination of the position of the double linking. Another method adopted for determining the position of an olefine bond is by an examination of the hydrobromide. If the bond is in the a/3 position the bromo-derivative of the saturated acid loses hydrogen bromide when treated with alkali and yields the original olefine acid. CH 3 .CH:CH.C0 2 H * CH 3 .CHBr.CH 2 .C0 2 H Crotonic acid /3-Bromobutyric acid CH 3 .CH:CH.C0 2 H. Crotonic acid. CONJUGATE DOUBLE BONDS 681 A /3y or 78 unsaturated acid also yields a hydrobromide, but when this is treated with alkalis hydrogen bromide is eliminated and a lactone formed. CH S .CH:CH.CH 2 .CO 2 H The presence of olefine linkings, as in maleic anhydride, in- creases to an appreciable extent the readiness with which the anhydride combines with water (Eweit and Sidgwick, J. C. S. 1910, 1677). An extremely simple method of determining whether the double bond is in the a/2 position or not, is by an examination of the rate of esterification of the unsaturated acid and of its saturated analogue by the catalytic method. If the un- saturated acid has a much lower rate of esterification than its reduction product the conclusion may be safely drawn that the double bond is in the a/2 position, as /3y unsaturated acids are esterified somewhat more quickly than their satu- rated analogues, and acids in which the double bond is still further removed from the carboxyl group have much the same esterification constants as the corresponding saturated acids (Sudborough and Gittins). For the stereochemistry of compounds containing only one ethylene linking, cf. p. 243. When two or more olefine bonds are present in the molecule, the isomerism is more complex. Not merely can we have structural isomerides, which differ in the relative positions of the olefine linkings, but also the num- ber of stereoisomerides increases. For compounds of type, Cab:C:Cab, see p. 634. C. Compounds with Conjugate Double Bonds. One of the most interesting groups containing two double linkings are the compounds with conjugate double bonds. Within recent years numerous experiments have been made with compounds con- taining two double bonds in the relative positions indicated by the formula E.CH:CH.CH:CH.E. These have been termed conjugated double bonds by Thiele, and extremely interesting results have been obtained by the study of the additive reactions of such compounds. It is and 682 L tJNSATtJRATtotf found that the atoms or radicals added on do not, as a rule, become simply attached to the carbon atoms 1 and 2 or 3 and 4, but to numbers 1 and 4; so that a new ethylene linkage is created in position 2 : 3. Thus cinnamylideneacetic and cinna- mylidenemalonic acids when reduced yield l:4-dihydro-deriva- tives (Ruber, B. 1904, 37, 3120) C 8 H 6 .CH:CH.CH:CH.C0 2 H + 2H -* C 6 H 6 .CH 2 .CH:CH.CH 2 .C0 2 H C 6 H 6 .CH:CH.CH:C(C0 2 H) 2 + 2H -* C 6 H 5 .CH 2 .CH:CH.CH(C0 2 H) 2 . Sorbic acid (p. 166) yields CH 3 .CH 2 .CH:CH.CH 2 .C0 2 H: similarly butadiene, CH 2 : CH CH : CH 2 , reacts with bromine, yielding l:4-dibromo-A 2:3 -butene, CH 2 Br . CH : CH . CH 2 Br. Similar results have been obtained when the double bonds are between carbon and oxygen; thus benzil, 6:C(C 6 H 6 ).C(C 6 H 6 ):6, when reduced under special conditions yields OHC(C 6 H 6 ): C(C 6 H 5 )-OH a/3-dihydroxy-stilbene. That additions do not always take place in the 1 : 4-positions is shown by the following examples: Methyl cinnamylidene- malonate adds on bromine in the 3: 4-positions and yields C 6 H 5 CHBr CHBr . CH : C(C0 2 Me) 2 (Henrichsen and Triepel, A. 1904, 336, 223). The addition of potassium hydrogen sul- phite to cinnamylidenemalonic acid occurs in the 1 : 2-position, and the product is C 6 H 6 CH : CH CH(SO S K) . CH(C0 2 H) 2 (Kohler, Am. 1904, 31, 243); similarly with hydrogen cyanide. Unsaturated aldoximes and ketoximes when reduced yield un- saturated amines, indicating that the addition of hydrogen K-CHiCH-CHiN-OH -f 4H + R.CH:CH.CH 2 -NH 2 -f H 2 O occurs in the 1: 2-position (Harries, A. 1903, 330, 193); a/3 unsaturated ketones also add on sulphinic acids in the 1:2 (carbonyl) position (Am. 1904, 31, 163). s-Diphenylbuta- diene, CHPh:CHCH:CHPh, also adds on bromine in the 1 : 2-position. Thick (A. 1889, 306, 87) has attempted to account for the DIVALENT CARBON 683 characteristic l:4-addition of most of the compounds with conjugated double bonds by his theory of partial valencies. It is supposed that when two atoms are united by a double bond the whole of the energy of the atoms is not used up, but that there is a slight residual affinity or partial valency which Thiele denotes by dotted lines, e.g.\ ECH:CHK. He considers the power of forming additive compounds is due to the presence of such partial valencies. Now in a system with two double bonds in positions 1:2 and 3:4 there are four partial valencies, and according to Thiele two of these, viz. 2 and 3, are supposed to have neu- tralized one another and only 1 and 4 are active. This is usually represented by the formula K.CH:CH.CH:CH.K, and hence the usual 1 : 4-addition with compounds containing conjugated double bonds. Thiele's theory does not account for the numerous exceptions mentioned above. Probably it is simpler to regard the compound as containing 4 residual valencies in the 1, 2, 3, 4 positions, and to conclude that the question as to which of these will be used up in the formation of an additive compound depends largely on the nature of the addenda and the nature of the groups already attached to the atoms numbered 1, 2, 3, and 4. The reaction between compounds with conjugated double bonds and Grignard's reagents consists in many cases of 1:4- addition. See Kohler (Am. 1904, 31, 642; 1905, 33, 21, 35, 153, 333; 34, 568; 1906, 35, 386; 36, 177, 529; 1907, 37, 369; 38, 511; 1910, 43, 412, 475). D. Compounds of Di- and Trivalent Carbon. Carbon monoxide may be written either as C:0 or CjO. In the first formula both carbon and oxygen atoms are represented as being divalent, and in the latter formula both are tetra- valent. It has been argued that the formula, C:0, is prob- ably the correct one, as when the monoxide forms additive compounds the two addenda become attached to carbon and not one to carbon and one to oxygen. Thus with chlorine we get carbonyl chloride, 0:C<CQj, the constitution of 684 L. tJNSATURATION which is determined by the fact that it reacts with alcohol, forming ethyl chloro-carbonate and finally ethyl carbonate, 0:C(OEt) 2 . With sodium hydroxide carbon monoxide gives rise to sodium formate: 0:C-hNaOH = O:C and with hydrogen chloride it yields the unstable formyl chloride, OlCxpi. Although vapour-density determinations indicate that in a mixture of the two gases very little com- bination has taken place, yet Gattermann 's synthesis of acid chlorides, by the action of a mixture of carbon monoxide and hydrogen chloride on aromatic compounds in the presence of aluminium chloride, proves that a small amount of an addi- tive compound exists, and that its structural formula is the one represented above. Carbylamines. On p. 104 the conclusion has been drawn that in the carbylamines (alkyl isocyanides) the alkjd group must be attached* to nitrogen and not to carbon, and therefore they are to be represented as R-N-C or RN:C. In the latter formula the carbon atom is represented as being di- valent, and the arguments used in support of this formula are similar to those used in the case of carbon monoxide, viz. the two addenda invariably unite with the carbon atom and not one with carbon and one with nitrogen. The following ex- amples can be given: (a) with chlorine: RN:CC1 9 ; (b) with /COPh acyl chlorides: RN:C<\ ; (c) with hydrogen sulphide: R-NrCH.SH = R.NH-CH:S (an alkylated thioformamide) ; (d) with oxygen: RN:C:0, alkyl isocyanates; (e) with sul- phur: R-N:C:S, mustard oils; (/) with Grignard reagents: T? ttf'C*/' . ~R "Nr-r*^ N ' C \MgI n.,0 E N ' C \H' an imino- derivative which is hydrolysed to an aldehyde, 0:CH.R; (g) with ethyl hypochlorite. Cf. Nef, A. 287, 273. Metallic Cyanides. Both nitriles and carbylamines are alkyl derivatives of hydrogen cyanide, and can be obtained by the action of alkyl iodides or potassium alkyl sulphates on different metallic cyanides, e.g. potassium cyanide and ethyl iodide yield ethyl cyanide, whereas the same iodide with silver cyanide yields mainly ethyl carbylamine. Although two series of alkyl derivatives exist> only one hydrogen METALLIC CYANIDES 685 cyanide is known. Certain of its reactions point to the nitrile structure H-C-N, and others to the carbylamine formula HN:C; it is a typical tautomeric substance. The view gene- rally held with regard to the metallic cyanides is that they have a carbylamine structure. The arguments used are briefly as follows: (1) The similarity between the additive reactions of metallic cyanides and those of carbylamines (a) with bromine potassium cyanide yields potassium bromide and cyanogen bromide; although an additive compound cannot be isolated, the reaction is in complete harmony with the view that an unstable compound, is formed which breaks up into KBr and N C Br; (b) po- tassium cyanide and benzoyl chloride yield benzoyl cyanide, N C CO CgH 5 , but here again an additive compound, K N : CC1 COC 6 H 5 , is probably first formed; (c) potassium cyanide combines with oxygen and sulphur in much the same manner as the carbylamines; (d) with ethyl hypochlorite a compound, HN : C(OEt) CN, ethyl cyano-imino- carbonate, is formed. The reaction can be represented as follows: K-NiC K-NiCCl-OEt K-N:C(OEt).CCl:NK -* KCl + K.N:C(OEt).CN. (2) Both alkyl carbylamines and alkali cyanides dissolve silver cyanide yielding double salts, whereas alkyl cyanides do not. (3) Tetramethylammonium cyanide, which probably has a constitution similar to that of the metallic cyanides, yields trimethylainine and methylcarbylamine when heated. This last argument by itself is of but little value, as a com- paratively high temperature is required and molecular rear- rangements could occur. Reactions of Metallic Cyanides. Formation of Nitriles and Carbylamines. The following reactions occur: HI '->.':. . -, - alkyl cyanides, K-C:N Potassium cyanide _ acyl cyanides, K- CO- C:N. B-COCl 1 . , alkyl carbvlamines, E,N:G Silver cyanide _ acy { B.-COC1 686 L. UNSATURATION The reactions cannot be due to the tautomerism of silver cyanide, as no cases are known where a heavy atom like silver can wander. The view that carbylamines are first formed by simple exchange in all cases, and then in three of the four reactions the carbylamine becomes transformed into a nitrile, is untenable, as carbylamines cannot be trans- formed into nitriles. The reverse process is also improbable, as carbylamines are formed from nitriles at high temperatures only. The views of Nef(A. 287, 274) as modified by Wade (J. C. S. 1902, 1596) are that in all four cases additive compounds are first formed. When the metallic radical in the cyanide is feebly positive, then feebly positive alkyl compounds combine with N, but negative acyl derivatives combine with C. With a strongly positive metallic atom in the cyanide, e.g. KCN, both alkyl and acyl derivatives combine with N. Thus with AgNC and EtI we have addition to N. Similarly with EtNC and EtI; but with AgNC and AcCl, and EtNC and AcCl, we have addition to C. With KNC and EtI and also with KCN and AcCl the addition is to C. K-NiC + Etl K.N:C< fc -> KI-fN:CEt Ag.N: Ag-N:C-fAcCl Ag-NiCK^ AgCl + N-C-Ac. It may appear remarkable that in reaction 2 the alkyl iodide adds on to the nitrogen atom and leaves the carbon divalent. Nef assumed that the conversion of the silver salt into carbylamine was an example of direct displacement, but Wade proves that dry silver cyanide is able to absorb methyl iodide at its boiling-point, yielding a viscid mass which evolves methylcarbylamine when more strongly heated. The consti- tution of this additive compound is based on a study of the products from alkyl iodides and aikylcarbylamines ; when hydrolysed these compounds yield small amounts of secondary amines, and hence, according to Wade, must be represented as: Me-N:C and similar formulae are given to the products from silver cyanide and alkyl iodides. METALLIO CYANIDES 687 Sidgivick (P. 1905, 120) concludes that in all cases addition takes place at the carbon atom: where M represents either K or Ag. Such a compound con- tains the grouping: characteristic of the oximes of aldehydes and of unsymmetri- cal ketones (cf. pp. 137, 428), and can therefore exist in syn- and anti- configurations. Potassium cyanide is supposed to yield the sytt-compound : E.C.I which readily loses potassium iodide, as both metal and halo- gen are on the same side of the molecule, and thus yields a nitrile. Silver cyanide, on the other hand, yields the anti- compound: E-C-I Ag-N. Silver iodide is not readily split off, as the metal and halogen are now on different sides of the molecule. It therefore undergoes the Beckmann transformation (p. 429), yielding: Ag-C.I E.N ' which loses silver iodide and forms C:NE, an alkyl carbyl- amine. Although the metallic cyanides are usually represented by a carbylamine structure, it does not follow that hydrogen cyanide is to be represented in a similar manner. Arguments based on a study of its physical and chemical properties have been brought forward; some point to the one, and others to the alternative formula, but probably, on the whole, the pro- perties are more in harmony with the nitrile structure, HC|N. It is possible that it may be, like the tautomeric substance, ethyl acetoacetate, a mixture of the two compounds but mainly nitrile. (For summary see Sidgwick, " The Organic Chemistry of Nitrogen", p. 209.) J?ulminic acid, C ; N OH, is known chiefly in the form of its 688 L. UNSATURATION silver and mercury salts. The latter was first prepared in 1800 by Howard, by the action of alcohol and nitric acid on mercuric nitrate. It crystallizes in lustrous prisms, explodes with great violence when heated or struck, and is largely used in the manufacture of percussion caps, dynamite cartridges, &c. In 1824 Gay-Lussac and Liebig showed that the silver salt had the same percentage composition as silver cyanate, and thus afforded one of the first examples of isomerism. They also showed that double salts, e.g. KAg(CNO) 2 , could be obtained. Various formulae have been proposed. KekuU suggested the formula N0 2 CH 2 .CN, riitroacetonitrile; Holle- mann suggested a glyoxime peroxide formula, CH CH N.O-O-N ; and Steiner in 1883 the formula OH.N:C:C:N.OH, di-iso- nitroso ethylene. It will be noticed that all these formulae represented the molecule as containing two carbon atoms. The reasons for this were: (1) It is obtained from ethyl alcohol. (2) With bromine or iodine it yields ethane derivatives. (3) As it forms double salts the acid was thought to be dibasic. Various arguments were brought forward in favour of and against the first two formulae, but the question has been definitely decided by the preparation of nitroacetonitrile (Steinkopf and Jjohrmann, B. 41, 1044) and of glyoxime per- oxide (Jomtschitsch, A. 347, 233), and showing that they differ from fulminic acid. The main argument in favour of Steiner's formula is that fulminates yield hydroxylamine when treated with concentrated hydrochloric acid, just as V. Meyer had previously shown that oximes do. Steiner was able to prove that the whole of the nitrogen can be removed in this way in the form of hydroxylamine, and also that formic acid is the second product: C 2 H 2 O 2 N 2 + 4H 2 O 2H 2 CO 2 + 2NH 2 OH. Such a reaction proved that KekuU's formula could not be correct. In 1894 Nef (A. 280, 303) suggested the simple formula C:NOH, now generally accepted, which represents the acid as the oxime of carbon monoxide. The following arguments were adduced: (1) By the action of one equivalent of hydrogen chloride on one of the silver salt, no trace of silver chloride is formed, but an additive product, which was shown to be the FULMINATES G89 chloride of formhydroxamic acid, or formyl- chloride oxime, C1CH:N.OH. This forms colourless crystals volatile at the ordinary temperature, and decomposes readily. With aniline it yields formanilide oxime, NHPh.CHrN.QH or NPh:CH- NH'OH. (2) It can be synthesized from a compound con taining one carbon atom, namely nitromethane. The mercuric salt of nitromethane, when heated with water, yields water and mercury fulminate: CH 2 :NO-OM H 2 O + C:N.OM. (3) With nitrous acid it yields methylnitrolic acid (p. 96). C:N.OH + H.N0 2 NO 2 -CH:N.OH. (4) According to Schott (B. 32, 3492; 36, 10, 322, 648), when benzene is treated with mercury fulminate and a mixture of anhydrous and hydrated aluminium chloride, benzaldoxime is formed (70 per cent). The water of the hydrated chloride liberates hydrogen chloride, which combines with the fulmi- nate, yielding the additive compound, OMN:CHC1, which then condenses with the benzene in the manner of the Friedel- Crafts reaction, yielding C 6 H 5 CH:N'OM, from which the free oxime is liberated by means of mineral acid. The hydrolysis of a fulminate to formic acid and hydroxyl- amine by means of hydrochloric acid is almost undoubtedly preceded by the formation of an additive compound: OH.N:CH.C1 + H 2 O OH-NzCH-OH OH.N:CH.OH + H 2 _* O:CH.QH + NH 2 OH. Free fulminic acid can be obtained by the action of an ex- cess of sulphuric acid on a solution of potassium fulminate and extraction with ether. It volatilizes with the ether when this is distilled, and readily polymerizes to meta-fulminic acid. Nef has pointed out the remarkable analogy between hydrogen cyanide and fulminic acid. No direct estimations of the mole- cular weight of fulminic acid have been made, but an indirect determination by L. Wohler (B. 1905, 38, 1351) points to the simple formula HCNO. The method is based upon the deter- mination of the value of van't Hofs dissociation factor i for the sodium salt in 0'2 to O'l Absolution. The value was found to be 1 -85, the usual value for the salt of a monobasic acid. Also the increase in molecular conductivity in passing from N/32 to JV/1024 solution was found to be 5 units, corresponding with Ostwald's value 4-8 for the salt of a monobasic acid. (B480) 2X 690 L. UNSATURATION The following has been suggested by Wieland as the prob- able course of the reaction in the preparation of a fulminate from ethyl alcohol: Oxidation to acetaldehyde, formation of isonitroso - acetaldehyde, oxidation to isonitroso - acetic acid, HO N : CH C0 2 H, nitration to nitro-isonitroso-acetic acid, de- composition into carbon dioxide and methylnitrolic acid, con- version of methylnitrolic acid into nitrous and fulminic acids. A polymer of fulminic acid, known as fulminuric acid, has been shown to be cyanonitroacetamide, NO 2 CH(CN) CO . NHa. Tervalent Carbon: Triphenyl- methyl. In attempting to prepare hexaphenylethane by the action of finely divided silver or zinc on triphenylchloromethane in benzene solution, Gom- berg (J. Am. 1900, 22, 757) obtained a substance which con- tained oxygen, but in the absence of air the product was free from oxygen, and when the solution was carefully evaporated a compound with pronounced unsaturated properties was iso- lated. It combines vigorously with oxygen, yielding the peroxide, CPhg-O-O-CPhg, m.-pt. 185-186, which is trans- formed by sulphuric acid into triphenylcarbinol ; it also com- bines with iodine, yielding triphenyliodomethane, and forms additive compounds with ethers, ketones, esters, nitriles, &c. It was suggested that these properties pointed to the formula, CPh 3 , for the hydrocarbon, a formula which contains a ter- valent carbon atom. The corresponding ion, CPh 3 , appears to be formed when triphenylchloromethane is dissolved in liquid sulphur dioxide, as such solutions are good conductors of the electric current. Molecular weight determinations by the cryo- scopic method point to the double formula, (CPh 3 ) 2 , for the hydrocarbon. Tschitschabin (B. 37, 4709) has suggested that the product is hexaphenylethane, and has supported this conclusion by a study of the properties of pentaphenylethane, which is somewhat unstable and readily attacked by oxygen, and is completely ruptured by hydrochloric acid at 150. Quinonoid formulae have also been suggested, the symmetrical formula I by Heintschel (B. 36, 320, 579), and formula II by Jacobson (B. 37, 196): (I) CPh 2 :0<g|:>CH.CH<:gg>C:CPh 2 (II) KETENS 691 According to Schmidlin (B. 41, 2471) two forms of triphenyl- methyl exist, a colourless and a yellow. When freshly dis- solved in benzene the solution is colourless but changes gradually to orange-yellow. The colour is destroyed by shaking the solution with air, but returns again on standing, and it is argued that the yellow form reacts with air more readily than the colourless compound. In solution there is an equilibrium between the colourless and coloured forms, and the equilibrium is displaced in favour of the colourless by lowering the temperature. The general view is that the equilibrium may be represented by the equation: CPh 3 .CPh s ^ 2CPh 3 ; Colourless Yellow and this view is supported by Wieland (B. 42, 3020), who shows that in naphthalene solution, which contains more of the yellow form than the benzene solution does, the molecular weight is much less than that required by the formula (CPh 3 ) 2 , indicating that the yellow compound presumably has the com- position CPh 3 . Schlenk, Weickel, and Herzenstein (A. 372, 1) have prepared a tri-diphenylmethyl, C(C 6 H 4 C 6 H 6 ) 3 , by the action of finely divided copper on tri-diphenylchloromethane, and have been able to show that in solution it is monomole- cular. The corresponding bimolecular form is not known. Its solutions have a deep-violet colour, and it reacts readily with oxygen, giving a colourless peroxide. Corresponding diphenyl-diphenylmethyl, CPh 2 C 6 H 4 Ph, and phenyl-di diphenylmethyl, CPh(C 6 H 4 'Ph) 2 , have been prepared; they exist in both coloured and colourless modifications. Just as colourless hexaphenylethane tends to break up into coloured triphenylmethyl, so pentaphenylethane when heated in anisole solution in absence of air breaks up into CPh 3 (yellow) and CHPh 2 ; the formation of the latter is proved by the formation of tetraphenylethane due to the union of two CHPh 2 radicals. E. Ketens. Wilsmore (J. C. S. 1907, 91, 1938; 1908, 93, 946) has isolated the simplest possible ketone, CH 2 :CO, which he terms keten, and which may be regarded as a new [anhy- dride of acetic acid. It is obtained by the action of a hot pla- tinum wire on acetic anhydride; numerous other substances are formed at the same time, but a 10-per-cent yield is obtained. It is a colourless gas at the ordinary temperature, has a char- acteristic odour, and reacts with hydrogen chloride, ammonia, 692 L. UNSATURATION and aniline, yielding acetyl chloride, acetamide, and acetanilide respectively. When kept for some time it polymerizes, yield- ing cyclohutane-l:3-dione, CH 2 <^Q>CH 2 , b.-pt. 126-127, which combines with water to acetoacetic acid (p. 226), and with aniline to acetoacetanilide (J. C. S. 1910, 1978). Homologues of keten, e.g. dimethyl-keten, (CH 3 ) 2 C : CO, and diphenyl-keten, (C 6 H 5 ) 2 C:CO (Staudinger, B. 1905, 38, 1735; 1906, 39, 968; 1907, 40, 1145, 1U9), have also been prepared. The method consists in the action of zinc on a-bromoisobutyryl bromide and diphenyl-chloroacetyl chloride respectively. The compounds are unstable and readily polymerize. Dimethyl- keten forms stable compounds with tertiary amines, and with water, alcohol or amines give isobutyric acid, its ester or amide : CMe 2 C:CO + HX The presence of a keten group, CHg'CO', is of great impor- tance in the syntheses of numerous cyclic compounds (cf. Collie, J. C. S. 1907, 91, 1806). The homologues are frequently divided into (a) aldoketens, (b) ketoketens. The aldo group comprises keten, its mono- alkyl substituted derivatives, and carbon suboxide. They are colourless, incapable of autoxidation, and are polymerized by pyridine. The keto group consists of the dialkylated deriva- tives. These are coloured, readily undergo autoxidation, and form additive compounds with tertiary amines, such as pyri- dine, quinoline, and acridine. These products from dialkyl ketens and tertiary amines are stable and have basic pro- perties; they contain two molecules of keten combined with one of the base, and the compound with quinoline is repre- sented as H CH CO.CMe 2 .CO-CMe 2 (A. 1910, 374, 1). They also form additive compounds with substances containing the groupings C:N and C:0, for ex- ample Schifs bases and quinones. Diphenyl keten and qui- none yield the /3-lactone, : C 6 H 4 CO, which decom- poses into C0 2 and : C 6 H 4 : CPhg, diphenyl-quinomethane, when heated (Staudinger, B. 1908, 906, 1355, H93). tJNSATtJRATION AND PHYSICAL PROPERTIES 603 Ethyl ethylketene-carboxylate, C0 2 Et-CEt:CO, is colour- less, and does not yield additive compounds, but readily poly- merizes, yielding a cyclobutane derivative. F. Unsaturation and Physical Properties. Unsaturation, especially in the case of compounds with conjugate linkings, produces a marked effect on numerous physical properties. The phenomena which have been most closely studied are those on the refraction and dispersion of light. The effect of such a conjugate linking as in CHMe : CH CH : CHMe, is to produce a considerable increase or exaltation in the specific and molecular refraction and dispersions. In the case men- tioned the molecular refraction is about one unit greater than the value calculated from the atomic refractions -f- two olefine linkings. The existence of such exaltation is frequently used as an argument in favour of the presence of conjugate link- ings (either two olefine or an olefine and carbonyl) in the com- pound examined. In the case of hexatriene, CH 2 :CHCH: CH '011:0112, the exaltation is 2*06 units. Exaltation is also observed when an acetylene linking is in conjugation with a carbonyl group. According to Moureau (Annales, 1906, [8], 7, 536), and Muller and Bauer (J. Chim. Phys. 1903, 1, 190), the exaltation in certain series of compounds increases with the negative character of the substituents. Little or no exaltation is met with in the case of benzene, furane, diacetyl, and similar compounds, although the formulae usually written for these compounds contain conjugate bonds. This may be due to special symmetrical ring structure or to mutual neutrali- zation of residual affinities. Unsaturated groups such as amino, vinyl and allyl, when present, in benzene compounds and directly attached to the nucleus, produce exaltation, probably owing to a readjustment of residual affinity. Exaltation is extremely well marked in compounds containing conjugate linkings, which, in their turn, are conjugate to the ethylene bonds in phenyl groups: e.g. diphenyl-butadiene, CHPh:CH CHiCHPh, has an exaltation of 15 units (Klages, B. 40, 1768); cinnamylideneacetic acid, CHPh : CH CH : CH C(OH) : 0, of 10-5 units, and diphenyl-hexatriene, CHPh:CH.CH:CH.CH: CHPh, of 24 units (Smedley, J. 0. S. 1908, 376). Some of the most accurate work on unsaturated compounds has been carried out by Auwers and Eisenlohr (J. pr. 82, 65; 84, 1, 37). They compare the specific refractions x 100, and not molecular refractions, and make use of the following values for atomic refractions n D as determined by Eisenlohr (Zeit. 694 LI. ALIPHATIC DIAZO ANt> TRlAZO-COMPOtrfcDS 75, 585): CH 2 = 4-618, C = 2-418, H = 1, O (in car myl) = 2-211, (in ethers) = 1-643, (in hydroxyl) = 1-525, Cl = 5-967, Br = 8-865, I = 13-900, define linking = 1-733, and acetylene linking = 2*398. They find that a single conjugation in a hydrocarbon produces an exaltation of approximately 1*9 units, but that this value is reduced to an appreciable extent by the introduction of substituents. The amount of this interference depends upon the number and position of the substiuients. In cinnamene and its /?-sub- stituted derivatives the exaltation is about TO, and when three substituents are present the exaltation is only 0-45. They conclude that for a given type of compound the exalta- tion is fairly constant, and within such limits the existence of the exaltation may be made use of in discussions bearing on constitution. When several pairs of conjugate linkings are present, it is found that the exaltation is much greater when these all form a single chain (cf. hexatriene) than when they are " crossed " as in Semicyclic double bonds (p. 574) and rings formed of three atoms, e.g. trimethylene, also produce optical exaltation. For effects of unsaturation on heats of combustion, see Auwers and Roth (A. 373, 239, 267). For effects of unsaturation on optical activity, see Frank- land and others, J. C. S. 1906, 1854, 1861; 1911, 2325; Hildich, J. C. S. 1908, 1, 700, 1388, 1618; 1909, 331, 1570, 1578; 1910, 1091; 1911, 218, 224; Zeit. phys. 1911, 77, 482; Rupe, A. 373, 121. LI. ALIPHATIC DIAZO- AND TEIAZO-COM POUNDS A. Diazo-compounds. By the action of nitrous acid on a solution of a salt of a primary aromatic amine, the important group of diazo or diazonium salts are formed. It is generally stated that aliphatic amino-compounds differ from the aromatic in this respect, and immediately yield the corresponding hy- droxy-compounds. A few aliphatic amino-compounds do, how- ever, yield diazo-derivatives with cold nitrous acid; one of the N\ best known of these compounds is ethyl diazo-acetate, - >CII- ALIPHATIC TRIAZO-COMPOUNDS 695 C0 2 Et (p. 212), a yellow oil, b.-pt. 141. It differs from the aromatic diazonium salts in having both nitrogen atoms at- tached to carbon, and may be regarded as the anhydride of a diazo hydroxide, OH N : N CBL- C0 2 Et. It is extremely re- active, and the N 2 group is readily replaced by I 2 , HC1, H^O, &c. With concentrated alkalis it yields bis-diazo- acetic acid: (Curtius, DurapsJcy, and E. Mutter, B. 1907). The simplest aliphatic diazo-compound is cliazo-methane, N -., which may be regarded as the anhydride of CH 3 N:N'OH. Diazo-methane is most conveniently prepared by decomposing nitroso-methyl-urethane, CH 3 N(NO) C0 2 Et, with alkali, the compound, CH 3 N:NOK, being formed as an intermediate product (Hantzsch and Lehmann, B. 1902. 35, 897). It is a yellow, odourless gas at atmospheric temperature, and is excessively poisonous. It is characterized by its re- activity, and will readily convert acids into methyl esters, alcohols and phenols into methyl ethers, aniline and its homo- logues into secondary amines, and aldehydes into ketones. It is also capable of uniting with unsaturated compounds, yielding heterocyclic derivatives, e.g.: CH N= CH.NH, CH 2 N= CH 2 .NH Cf. p. 528. B. Triazo-compoimds. Forster (J. C. S. 1908, 93, 72, 669, 1070, 1174, 185$, 1865) has obtained a number of fairly simple aliphatic triazo-derivatives containing the univalent grouping, .. ;>N. Ethyl triazo-acetate, N 8 -CH 2 .C0 2 C 2 H 5 , ob- N/ tained by the action of sodium azide, NaN 8 , on an alcoholic solution of ethyl chloro-acetate, is a colourless liquid, b.-pt. 44-46 under 2 mm. pressure, and has a sweet odour sugges- tive of chloroform. From this ester triazo-acetic acid, m.-pt. 16, and almost as strong an acid as bromo-acetic, and triazo- acetamide, m.-pt. 58, have been obtained by the ordinary 696 LI. ALIPHATIC 1>IAZO- AND TRtAZO-COMPOUNDS methods. Triazo-acetone, acetonyl-azoimide, N 3 CH 2 CO CH 3 , obtained from chloro-acetone, is a colourless liquid, b.-pt. 54 under 2 mm. pressure. It has the properties of a ketone, e.g. yields a semicarbazone, m.-pt. 152, and is instantly decom- posed by alkalis. Ethyl a-triazo-propionate and the isomeric /^-compound have been prepared, and also a-triazo-propionic add, CH 3 CHN 3 C0 2 H, the last of which has been resolved into optically active components. Ethyl f$-triazo-propionate is so readily decomposed by alkalis that the corresponding acid and amide have not been prepared. Allyt-azoimide, CH 2 :CHCH 2 Nj, b.-pt. 76-5; triazo-ethyl alcohol, N 3 - CH 2 . CH 2 - OH, b.-pt. 60/8 mm.; triazo-acetaldehyde, an oil, together with numerous esters derived from triazo-ethyl alcohol, have been prepared. Bis-triazo- compounds can be obtained, e.g. bis -triazo- ethane, N 3 .CH 2 .CH 2 .N 3 , and ethyl bis-triazo-acetate, CH(N 3 ) 2 C0 2 Et, but are extremely explosive. Triazo-malonic acid and ethyl triazo-acetoacetate appear to be incapable of existence, but substituted derivatives, e.g. CH 3 CO-CN 3 Me-C0 2 Et, and even a bis -triazo -compound, CH 3 CO C(N 3 ) 2 (XXEt, are known. Triazo-ethylene, N 3 CH:CH 2 , can be obtained by eliminating hydrogen iodide from triazo-ethyl iodide. It is a pale-yellow liquid, b.-pt. 26, and yields an oily dibromide. Numerous aromatic triazo-compounds have also been prepared, mainly from diazonium salts. (Cf. J. C. S. 1907, 855, 1350; 1909, 183; 1910, 126, 254, 1056, 1360, 2570.) Staudinger and Kupfer (R 1911, 44, 2197) and /. Thide (ibid. 2522) suggest that aliphatic diazo-compounds have an open-chain structure, e.g. diazo-methane, CH 2 :N|N, and like the aromatic diazonium salts contain a quinquevalent nitrogen atom. The arguments brought forward are: (1) The fact that the diazo-compounds can be obtained by the oxidation of hydrazones of ketones: H 2 0. (2) The azo group is reactive, yet in the numerous reactions of the aliphatic diazo-compound such a group does not take part. In a similar manner hydrazoic acid and its derivatives are represented by open-chain formulae, e.g. HN:N|N. Such a structure accounts for the fact that by the action of Grignard reagents azides yield diazo-amino-compounds : R-N:N:N > R-NiN-NHR'. INDEX a= ana-position, 545. ac=alicyclic, 500. ar= aromatic, 500. Abietic acid, 591. Absorption spectra, 647. . Acenaphthene, 504. Acet-hydrazide, 185. Acetal, 129. Acetaldehyde, 128. Acetaldehyde-semicarbazone, 136. Acetaldoxime, 137. Acetals, 125. Acetamide, 185. Acetamidine, 187. Acetamido-chloride, 185. Acetanilide, 382. Acetates, 151. Acetic acid, 18, 140, 149. Acetic anhydride, 181. Acetic fermentation, 150. Acetimido-chloride, 186. Acetimido-thio-methyl, 187. Aceto-acetanilide, 543. Aceto-acetic acid, 223, 226. Aceto-acetic ester, 226. Aceto-acetic ester syntheses, 228. Aceto-bromamide, 183. Aceto-chloroimide, 186. Aceto-malpnic ester, 229. Aceto-nitrile, 102. Aceto-phenetidine, 415. Aceto-phenone, 427. Aceto-phenone-acetone, 427. Aceto-phenone oxime, 427. Aceto-phenone phenyl-hydrazone, 427. Aceto-succinic ester, 229. Aceto-tartaric acid, 253. Acetone, 136. Acetone-dicarboxylic acid, 261. Acetone-dioxalic acid, 533. Acetone peroxide, 181. Acetone-phenyl-hydrazone, 135. Acetone-semicarbazone, 136. Acetonyl-acetone, 221. Acetoxime, 137. Acetoluidide, 382. Aceturic acid, 212. Acetyl, 147. Acetyl-acetone, 221, 544, 655. Acetyl-acetone, constitution of, 644, 647. Acetyl chloride, 179. Acetyl cyanide, 179. Acetyl-diphenylamine, 377, Acetyl glycollic acid, 209. Acetyl hydride, 128. Acetyl oxide, 180. Acetyl peroxide, 181. Acetyl-phenyl-hydrazide, 398, Acetyl-urea, 285. Acetylaminophenol, 458. Acetylene, 52. Acetylene-dicarboxylic acid, 247. Acetylene series, 49. Achroo-dextrine, 319. Acid amides, 182. Acid anhydrides, 180. Acid azides, 185. Acid bromides, 180. Acid chlorides, 178, 684. Acid derivatives, 171. Acid esters, 91, 97. Acid green, 484. Acid hydrazides, 185. Acid hydrolysis, 227. Acid salts, 144. Acid violet, 489. Acids, aromatic, 435. Acids, fatty, 140. Aconitic acid, 262. Acridine, 548. Acridine yellow, 549. Acridinic acid, 548. Acridonium iodides, 549. Acrolei'n, 130. Acrolei'n-ammonia, 130. Acrolei'n-aniline, 542. a-Acrosazone, 312. a-Acrose, 312. a-Acrosone, 312. Acrylic acid, 161, 164. Active valeric acid, 154. Acyl derivatives of ethyl aceto-acetate, 229. Acyl oxides, 180. Acyl ureas, 285 et seq. Acyls, 147. Additive compounds of aldehydes, 124-126, Additive reactions of acetylenes, 50. Additive reactions of nitriles, 101. Additive reactions of olefines, 44. Adenine, 293, 599. Adipic acid, 231. ^Esculetin, 593. ^Esculin, 593. Alanine, 211, 215, 596. Alanylglycyl-glycine, 597. Albumins, 594, 599. 698 INDEX Albumins, hydrolysis of, 595. Albumins, oxidation of, 595. Albumoses, 598. Alcohol, 75. Alcohol, constitution of, 17. Alcohol of crystallization, 79. Alcoholic fermentation, 76, 304, 666. Alcohols, aliphatic, 65. Alcohols, aromatic, 421. Alcoholysis, 177. Aldehyde, 128. Aldehyde-acids, 204, 222. Aldehyde-ammonia, 125. Aldehyde "condensations", 126-127. Aldehyde-phenyl-hydrazone, 127. Aldehyde resin, 126. Aldehydes, aliphatic, 1 22 et seq. Aldehydes, aromatic, 423. Aldehydes, the fuchsine test for, 127, 128. Aldehydic acids, 222. Aldohexoses, 307. Aldoketens, 692. Aldol, 131, 220. Aldol "condensations", 131. Aldoses, 300. Aldoximes of the fatty series, 127, 137. Aliphatic compounds, 24, 321. Alizarin, 509. Alizarin black, 503. Alizarin blue, 510. Alizarin bordeaux, 510. Alizarin cyanine, 510. Alizarin orange, 510. Alkaloids, 554 et seq. Alkaloids from dead bodies, 196, 598. Alkarsin, 116. Alkyl, 22, 366. Alkyl cyanides, 100. Alkyl hydrogen sulphates, 98. Aikyl hydrosulphides, 88. Alkyl-hydroxylamines, HI. Alkyl-malonic acids, 237. Alkyl nitrites, 94. Alkyl salt, 74, 145. Alkyl sulphates, 98. Alkyl sulphides, 88. Alkyl sulphites, 98. Alkylated ureas, 284. Alkylenes, 22, 42, 189. Allantoin, 289. Allene, 53. Allo-cmnamic acid, 454. Allophanic acid, 285. Alloxan, 288. Alloxanic acid, 288, Alloxantin, 288. Allyl alcohol, 82. Allyl bromide, 56, 65. Allyl chloride, 56, 65. Allyl ether, 87. Allyl iodide, 56, 65. Allyl "mustard ou " = allyl Jsothiocyanate, An 7 ?' 59 3> A y -Py.'-'dine, 538, 557. Allyl sulphide, 91. Allyl thiocyanate, 276. Allylene, 53. Alphyl, 22, 366. Aluminium amalgam as a reducing agent 609. Aluminium chloride, action of; see Frie~ del-Crafts' synthesis. Aluminium methyl, 120. A.malic acid, 289. Amber, 591. Amethyst violet, 53. Amides of carbonic acid, 281. Amides of malic acid, 248. Amides of the fatty acids, 182. Amidines, 187. Amido, 182 ; see also Amino-group, Amido chlorides, 185. Amidoximes, 188. Amines, aliphatic, 104, 677. Amines, aromatic, 366. Amino-acetic acid, 211. Ammo-acetone, 136. Amino-acids, 211. Amino-azo-benzene, 397, 400. Amino-azo-compounds, 393, 400. Amino-azo-naphthalene, 500. Amino-benzaldehydes, 426. Amino-benzene, 372. Amino-benzene-sulphonic acids, 405. Amino-benzoic acids, 449, 451. Amino-benzoyl-formic acid, 462, 522. Amino-caproic acid = Leucine, 216, 596. Amino-cinnamic acids, 456. Amino-cinnamic aldehyde, 543. Amino-derivatives, aromatic, 366. Amino-dimethyl-aniline, 378. Amino-ethane acid, 211. Amino-ethyl-sulphonic acid, 197. Amino-glutaric-acid, 249, 596. Amino-group, 104. Amino-guanidine, 297. Amino-hexamethylene, 373. [596- a-amino-/3-hydroxy-propionic acid, 218, Amino-hypoxanthine, 293. Amino-isobutyl-acetic acid, 596. Amino-ketones, 136. Amino-mandelic acid lactam, 522, 525. Amino-mesitylene, 367. Ammo-naphthalenes, 499. Amino-naphthols, 502. Amino-naphthol-sulphonic acid, 502. Amino-naphthp-tolazine, 551. Amino-oxypurine, 293. Amino-phenols, 415. Amino-phenyl-acetic acids, 452. Amino-phenyl-glyoxylic acid, 462. Amino-propionic acid; see Alanine, 596 Amino-purme = Adem'ne, 293. Amino-pyridine, 558. Amino-succinic acid, 249, 596. Amino-sugars, 596. Amino-thiazole, 530. Amino-th jo-lactic SiC\A Cy stein, 596. Amino^thiophene, 519. Amino-trimethyl-benzenes, 367, Amiiio-triphenyl-methane, 483. Ammclide, 277. Ammeline, 277. Ammonium acetate, 151. Ammonium cyanate, 273. Ammonium ferri-thiocyanate, 276. INDEX 699 Ammonium formate, 148. Ammonium thiocyanate, 275. Amphoteric, 451. Amygdalin, 267, 423, 592. Amyl acetate, 178. Amyl alcohols, 67, 80, 669. Amyl nitrite, 94. Amylase, 671. Amylene glycols, 193. Amylenes, 43, 49. Amylo-dextrme, 319. Amyloid, 317. Amylum, 319. Analysis, elementary, 4. Analysis, qualitative, 2. Analysis, quantitative, 4. Ana-position, the, 545. Angelic acid, 161, 165. Anhydrides of the fatty acids, 180. Anilic acids, 382. Anilide of j^-toluic acid, 429. Anilides, 370, 381. Aniline, 367, 372. Aniline, oxidation of, 617. Aniline blue, 489. Aniline yellow, 401. Anilino-quinones, 433. Anisaldehyde, 429. Anisic acid, 459. Anisidines, 415. Anisole, 407, 412. Anisyl alcohol, 429. Anomalous electric absorption, 655. Anthracene, 471, 504. Anthracene brown, 510. Anthragallol, 510. Anthranil, 452. Anthranilic acid, 452. Anthranol, 508. Anthrapurpurin, 510. Anthraquinone, 477, 508. Anthraquinone-sulphonic acids, 508. Anthrarobin, 510. Anthrols, 508. Anti-albumoses, 598. ^4w^'-aldoximes, 139, 428. Anti-dia.z.0 compounds, 391. Anti-febrine, 383. Antimony pentamethyl, 117. Antipyrine, 528. Aposafranines, 553. Arabinose, 219, 306. Arabitol, 202. Arabonic acid, 219. Arachidic acid, 140, 157. Arbutin, 593. Arpfinine, 596. Ansto-quimne, 560. Aromatic acids, 435 ei seq. Aromatic compounds, 321. Aromatic nitriles, 438. Aromatic properties, 328. Arsenic compounds, 115. Arsines, 115. A rsonium compounds, 115. Aryl, 366. Arylamines, 366. Asparagine, 248. Aspartic acid, 249, 596. Asphalt, 42. Asymmetric carbon atoms, 154, 213, 250, 307, 461. ^ Asymmetric synthesis, 660. Atomic refractions; 643, 693. Atomic volumes, 640. Atropic acid, 443, 456. Atropine, 565. Aurichlorides, 107, 370= Aurine, 500. Australene, 582. Auxochromes, 678. Azealic acid, 165. Azo-benzene, 394, 396. Azo-compounds, aromatic, 396. Azo-dyes, 389, 399. Azo-dyes of the naphthalene series, 502 Azo-naphthalene, 501. Azo-phenines, 434. Azo-phenyl-ethyl, 397. Azo-phenylene, 551. Azoxy-benzene, 394, 395. Azoxy-compounds, 394. Bacillus butylicus, 152. Baeyer s tension theory, 323. Barbituric acid, 288. Beckmann molecular transformation, the. 137. 139. 429. 479. 687- Beer, 78. Behemc acid, 140, 157. Benzal chloride, 358. Benzaldehyde, 4231,592. Benzaldehyde-<rfanhydrin, 424. Benzaldehyde-phenyl-hydrazone, 426. Benzaldpximes, 426. Benzamide, 446. Benzamino-acetic acid, 447. Benzanilide, 446. Benz-a#-aldoxime, 429. Benzazide, 447. Benzazurine, 474. Benzene, 341, 345, 350, 433. Benzene, constitution of, 332. Benzene, formation, 341, 350. Benzene-azo-benzene, 396. Benzene-azo-naphthylamine, 502. Benzene-carboxylic acid = I}enzoic acid, 421, 444. Benzene derivatives, 327. Benzene derivatives, formation, 341, 344. Benzene derivatives, isomerism, 332 et seq. Benzene derivatives, occurrence, 341. Benzene-diazoic acid, 388. Benzene-diazoimide, 389. Benzene-diazonium perbromide, 389. Benzene-dicarboxylic acids, 464. Benzene-disulphonic acids, 406. Benzene disulphoxide, 413. Benzene formulae, 334 et seq. Benzene hexabrormde, 354. Benzene-hexacarboxylic acid, 470. Benzene hexachloride, 354. Benzene hydrocarbons, 344 et seq. Benzene hydrocarbons, constitution of 347- 700 INDEX Benzene hydrocarbons, oxidation of, 348. Benzene hydrocarbons, reduction of, 348. Benzene-methylal, 421, 423. Benzene-methylol, 421. Benzene nucleus, 328. Benzene of crystallization, 481. Benzene-sulphinic acid, 405. Benzene sulphonamide, 404. Benzene-sulphonic acidi 403. Benzene-sulphonic chloride, 404. Benzene-tetracarboxylic acids, 470. Benzene-tricarboxylic acids, 470. Benzene-trisulphonic acids, 406. Benzhydrazide, 447. Benzhydrol, 474, 476. Benzidam, 372. Benzidine, 395, 472. Benzidine-sulphonic acids, 473. Benzil, 479. Benzil-oximes, 479. Benzilic acid, 476, 480. Benzimido-azoles, 380. Benzoic acid, 443, 444. Benzoic anhydride, 446. Benzoic esters, 445. Benzoin, 425, 479. Benzoline, 42. Benzo-nitrile, 447. Benzo-peroxide, 446. Benzo-phenone, 428, 474. Benzophenone-carboxylic acid, 476. Benzo-purpurine 4 B, 474. Benzoquinones, 431, 433. Benzo-thiophene, 521. Benzo-^-toluidide, 429. Benzo-trichloride, 358. Benzoyl-acetic acid, 463. Benzoyl-acetone, 427. Benzoyl-azimide, 447. Benzoyl-benzoic acids, 476. Benzoyl chloride, 446. Benzoyl cyanide, 462. Benzoyl-ecgonine methyl ester, 566. Benzoyl-formic acid, 427, 462. Benzoyl-glycocoll; see Hippuric acid, 447. Benzoyl-nydrazine, 447. Benzoyl peroxide, 446. Benzoyl-salicin, 593. Benz-syn-aldoxime, 429. Benz^-toluidide, <pg. Benzyl-aceto-acetic ester, 441. Benzyl-alcohol, 421, 422. Benzyl-benzene ; see Diphenyl-methane. Benzyl-benzoate, 446. Benzyl chloride, 358. Benzyl cyanide, 452. Benzylamine, 367, 383. Benzylideneacetone, 428. Benzylidene-aceto-phenone, 428. Benzylidene-aniline, 371. Benzylphenylallylmethyl-ammonium d- camphor-sulphonate, 632. Berberine, 563. BetaYne, 212. Biebrich scarlet, 402, 503. Bilineurine, 196. Birotation, 309. Bis-azo-dyes, 402. Bis-diazo-acetic acid, 695. Bismarck brown, 401. Bismuth compound, 118. Bitter almond oil, 423. Bitter-almond-oil green, 484. Biuret, 289. Blomstrand formula, 385. Blood colouring- matter, 600. Boiling-point, 26, 635. Bonds, change in ; see Desmotropism, 227, 650, 651. Bone glue, 579. Bone oil, 518, 535. Borneo camphor, 588. Borneol, 588. Bornyl chloride, 584, 589. Bornyl iodide, 584. Bornylene, 584. Boron compounds, 118. Brassidic acid, 166. Brilliant black, 503. Brilliant green, 484. Brom-anilines, 374. Brom-anthraqmnones, 509. Bromacetic acid, 167. Bromination, 55, 56, 169, 356. Bromine as an oxidizing agent, 625. Bromo-benzene, 3^4. Bromo-benzoic acids, 449. Bromo-benzyl bromide, 505. Bromo-camphor, 588. Bromo-camphoric acid, 588. Bromo-cinnamic acids, 455. Bromo-ethylene, 65. Bromo-naphthalene, 498. Bromo-nitro-benzenes, 362. Bromo-nitro-camphors, 657, 658. Bromo-phenols, 413. Bromo-phenyl hydrazine, 399. Bromo-phenyl-mtromethane, 664. Bromo-propionic acids, 167. Bromo-propyl-aldehyde, 130. Bromo-succmic acids, 241. Bromo-terpane-one, 590. Bromoform, 56, 63. Brucine, 565. Butadiene, 682. Butadiine, 53. Butane acid, 152. Butane di-acid, 238. Butane-diamine, 195. Butane-diol di-acid, 249. Butane-dione, 221. Butane-tetrol, 202. Butanes, 30, 38. Butanol, 73. Butanol di-acid, 247. Butanone, 137. Butanone acid, 223. Butanone di-acid, 260. 2-Butene-i-acid, 164. i-Butene;4-acicl, 165. Butene di-acids, 242. Butenes^Butylenes, 43, 48. Butine di-acid, 247. Butyl-acridine, 548. Butyl alcohols, 67, 80. Butyl bromides, 56, 60. INDEX 701 Butyl chlorides, 56, 60. Butyl iodides, 56, 60. Butylamines, no. Butylene glycols, 193. -Butyric acid, 140, 152. Butyric fermentation, 152. Butyro-lactpne, 240. Butyro-nitrile, 102. Butyryl, 147. Cacodyl, 116, 117. Cacodyl chlorides, 116. Cacodyl compounds, 116-117. Cacodyl oxide, 116, 117. Cacodylic acid, 117. Cadayerine, 196, 598. Cadet s liquid, 1 16. Caffeic acid, 464. Caffeine, 295. Cairplin, 546. Calcium carbide, 52. Calcium cyanamide, 278. Calcium glucosate, 302. Camphane, 584. Camphanic acid, 588. Camphene, 584. Camphenilone, 584. Campholene cyanide, 586. Campholenic acid, 586. Camphor, 585. Camphor, artificial, 582. Camphor, synthesis of, 587. Camphor-oxime, 585. Camphoramic acid, 588. Camphoric acid, 586, 588. Camphoronic acid, 586. Camphylamine, 586. Cane sugar, 314. Capillarity constants, 665. Capric acid, 157. Caprilic acid, 157. Caproic acid, 140, 157. Caramel, 315. Carbamic acid, 281, 282. Carbamic chloride, 282. Carbamic compounds, 282. Carbamic esters, 282. Carbamide, 281, 282, 595. Carbanilide, 383. Carbazole, 473. Carbinol, 73. Carbocinchomeronic acid, 560, Carbocyclic compounds, 322. Carbohydrates, 298 et seq. Carbolic acid, 411. Carbon, detection of, 2. Carbon, estimation of, 4. Carbon monoxide, 683. Carbon monoxide-haemoglobin, 600. Carbon oxychloride, 280. Carbon suboxide, 238. Carbon tetrabromide, 56. Carbon tetrachloride, <;6, 64, 281. Carbonic acid, derivatives of, 279. Carbonic acid, esters of, 279, 280. Carbonyl chloride, 280, 683. Carbostyril, 453, 456, 43, 546. Carbostyril, constitution of, 649. Carboxylic acids, aromatic, 435. Carboxylic acids, fatty, 139. Carboxylic group, 140. Carbylamines, 102. Carbylamines, constitution of, 103, 684, Carone, 590. Caronic acid, 590. Carvacrol, 408, 417, 573. Carvene, 568. Carvenone, 590. Carvestrene, 576. Carvo-menthol, 579. Carvone, 573, 577, 579. Carvotanacetone, 577. Carvoxime, 575, 576. Casein, 599. Caseinogen, 599. Catalytic dehydration, 674. Catalytic oxidation, 674. Catalytic reduction, 610. Catechol, 408, 4x7. Cellulose, 317. Centric formula of benzene, 335. Cerotene, 43, 49. Cerotic acid, 140, 157, 158. Ceryl alcohol, 81. Ceryl cerotate, 178. Cetene, 43. Cetyl alcohol, 81. Cetvl palmitate, 178. Chain isomerism, 87. Chains, closed, 20, 24, 321. Chains, open, 20, 321. Chalcone, 428. Chelidonic acid, 533. Chemical retardation, 175, 449. Chlor-acetanilide, 373. Chlor-acetic acids, 167, 170, 210. Chloracetyl chloride, 210. Chloral, 129. Chloral alcoholate, 130. Chloral hydrate, 130. Chloranil, 432. Chloranilic acid, 433. Chlorhydrins, 193, 199. Chlorination, 56, 356. Chlorine as an oxidizing agent, 625. Chloro-aceto-acetic ester, 230. Chloro-amylamine, 535. Chloro-aniline, 373. Chloro-benzene, 336. Chloro-benzoic acid, 448, 449. Chloro-bromo-benzenes, 358. Chloro-butene acid, 171. Chloro-camphor, 568- Chloro-carbonic acid, 280. Chloro-carbonic ester, 280. Chloro-crotonic acids, 171. Chloro-ethane acid, 170. Chloro-formic acid, 170, 280. Chloro-malonic ester, 238. Chloro-methane-oxy-methanol, 128, Chloro-methanol, 128. Chloro-methyl alcohol, 128. Chloro-naphthalenes, 498. Chloro-nitro-benzenes, 362, Chloro-phenols, 413. Chloro-picrin, 97. 702 INDEX Chloro-propane-dfols, 200. Chloro-propene, 65. Chloro-propionic acids, 167, 171. Chloro-propylene, 65. Chloro-pyridine, 536. Chloroform, 56, 63. Cholestrophane, 287. Choline, 196. Chondrin, 599. Chromic anhydride as an oxidizing agent, 620. Chromogene, 399. Chromone, 541. Chromophores, 399. Chromo-proteins, 600. [620. Chromyl chloride as an oxidizing agent, Chrysamine, 473. Chrysaniline, 548. Chrysene, 512. Chrysin, 541. Chrysoidine, 401. Chrysoidines, 400. Cinchene, 560. Cinchomeronio acid, 540. Cinchona bases, 558. Cinchonidine, 560. Cinchonine, 560. Cinchoninic acid, 560. Cineol, 581. Cinnamene, 353. Cinnamenyl radical, 456. Cinnamic acids, 443, 454. Cinnamic alcohol, 422. Cinnamic aldehyde, 426. Cinnamo-carboxylic acid, 502. Cinnamon, oil of, 426. Cinnamyl radical, 456. Cinnamylideneacetic acid, 682. Cinnamylidenemalonic acid, 682. "Cis-" form, 246, 326. Citral, 570. Citrazinic acid, 263. Citrene, 368. Citric acid, 262. Citric esters, 262. Citron, oil of, 568. Citronellal, 569. Classen reaction, 225. Classification of organic compounds, 23, 321. Closed chains (rings), 20, 24, 321 et seq. Clupeine, 596. Cocaine, 566. Codeine, 564. Co-enzymes, 667, 668. Collidines, 539. Collodion, 317. Colophonium, 581, 591. Combustion of hydrocarbons, 36. Complex cyanides, 269. Conchinine, 60. " Condensation ", 126. Condensed benzene nuclei, 471 et seq. Configuration, spatial, 155. "Congo "(dye), 473. Coniferin, 430, 493. Comferyl alcohol, 429, 430, 493. Conune, 538, 557. Conjugate double bonds, 681, 693. Constitution of fructose, 311. Constitution of glucose, 310. Constitution of organic compounds, 16. Constitutional formula, 17. Continuous formation of ether, 84. Conyrine, 538. Copellidine, 540. Copper powder and hydrogen as a re- ducing agent, 611. Copper-zinc couple, 35. Coriandrol, 572. Corydaline, 563. Cotarnine, 562. Coumaric acids, 443, 463. Coumarilic acid, 520. Coumarin, 463. Coumarinic acid, 463. Coumarone, 520. Coumarone dibromide, 520. Coumarone picrate, 520. Creatine, 298. Creatinine, 298. Cremor tartari, 253. Creosol, 419. Cresols, 408, 416. Crotonic acids, 161, 164. Crotonic aldehyde, 130. Cryoscopic method, 10. Crystal violet, 488. Crystalline, 372. Cumene, 345, 352. Cupric ferrocyanide, 269. Cyamelide, 271. Cyanamide, 277. Cyanates, 271. Cyanhydrins, 126, 135, 206. Cyanic acid, 273. Cyanic ester, 273. Cyanides, metallic, 269 et seq. Cyanines, 546. Cyanmethine, 102. Cyano-acetic acid, 167, 171. Cyano-carbonic ester, 237. Cyano-fatty acids, 170. Cyano-nitroacetamide, 690. Cyano-propipnic acids, 171. Cyano-pyridine, 537-538. Cyanogen, 237, 266. Cyanogen bromide, 272. Cyanogen chloride, 272. Cyanogen compounds, 263 et seq. Cyanogen iodide, 272. Cyanogenetic glucosides, 592. Cyanol, 372. Cyanuramide, 277. Cyanuric acid, 274. Cyanuric chloride, 271. Cyanuric esters, 273. Cyclic ammonium salts, 197, 212. Cyclic compounds, 24, 321. Cyclic ureides, 286. Cyclo-butane, 322. Cyclo-butane-dione, 692. Cyclo-hexane-diol, 419. Cyclo-hexane-dione, 432. Cyclo-propane, 322. Cymene, 345, 352, 572. INDEX 703 Cystein, 596. Cystin, 596. d= dextro-rotatory, 154, 249. Deca-tetrine di-acid, 247. Decane, 30. Decyl alcohol, 67. Decylene, 43. Dehydration, catalytic, 674-677. Deka-hydronaphthalene, 497. Deoxy-benzoi'n, 479. Dephlegmators, 78. Desmotropism, 227, 650, 651. Determination of configuration of hex- oses, 308. Determination of configuration of olefine compounds, 246. Determination of configuration of oximes, 139, 429,479. Dextrmes, 319. Dextro-limonene, 575. Dextro-tartaric acid, 252 et seg. Dextrose, 309. Dhurrin, 592. Diacetamide, 185. Diacetanilide, 383. Diaceto-acetic ester, 229. Diacetoglutaric acid, 261. Diaceto-succinic acid, 261. Diaceto-succinic ester, 229. Diacetyl, 205, 221. Diacetyl-dihydrazone, 222. Diacetyl-osazone, 222. Diacetylene, 33. Diacetylene-dicarboxylic acid, 247. Diagonal formula of benzene, 336. Di-aldehydes, 97, 204, 221. Di-allyl, 53. Dialuric acid, 288. Diamide ; see Hydrazine. Diamines, 189, 194, 195. Diamines, aromatic, 380. Diamino-acetic acid, 596. Diamino-azo-benzene, 401. Diamino-azo-benzene hydrochloride, 401. Diamino-caproic acid, 219, 596. Diamino-dimethyl-acridine, 548. Diamino-diphenyl, 472, 473. Diamino-diphenyl-methane, 476. Diamino-phenazine, 552. Diamino-phenyl-acridme, 548. Diamino-stilbene, 478. Diamino-triphenyl-methane, 483. Diamino-valeric acid = Ornithine, 219,596. Dianilino-quinone-dianile, 434. Di-anisidine, 474. Diastase, 77, 671. Diazines, 549. Diazo-amino-benzene, 394. Diazo-amino-compounds, 392 et seg. Diazo-amino-naphthalene, 500. Diazo-benzene-sulphonic acid, 406. Diazo-benzoic acids, 451. Diazo-compounds, 384, 390. Diazo-compounds, fatty, 212, 694. Diazo-compounds, isomerism of, 391. Diazo-guanidine, 298. Diazo-methane, 695. Djazonium salts, 384. Diazotizing, 386. Dibasic acids, saturated, 231. Dibenzyl, 471, 477. Dibromo-acetic acid, 167. Dibromo-benzeries, 357. Dibromo-propionic acids, 167. Dibromo-propyl aldehyde, 130. Dibromo-succinic acids, 241. Dicetyl ether, 87. Dichlor-hydrins ; see Chlorhydrins. Dichloro-acetic acid, 167, 170. Dichloro-aceto-acetic ester, 230. Dichloro-butyro-lactone, 240. Dichloro-isoquinoline, 547. Dichloro-maleic acid, 343. Dichloro-propane-ols, 200. Dichromates as oxidizing agents, 620 Diethyl ; see Normal butane, 38. Diethyl-aniline, 367, 379. Diethyl-butyro-lactone, 240. Diethyl-cyanamide, 278. Diethyl-disulphide, 89. Diethyl ether, 85. Diethyl-hydrazine, 112. Diethyl ketone, 133. Diethyl nitrosamme, 112. Diethyl peroxide, 181. Diethyl-semi-carbazide, ii2 Diethyl sulphide, 88. Diethyl sulphone, 89. Diethyl sulphoxide, 89. Diethyl-thio-urea, 296. Diethyl-urea, 112, 285. Diethylamine, no, in. Diethylamino-phenol, 415. Dieth}dene-diamine, 195. DigitaleYn, 593. Digitalin, 593. Digitomn, 593. Digitoxin, 593. Di-glycollic acid, 210. Di-glycollic anhydride, 210. Di-hydrazones, 221, 301. Di-hydric alcohols, 188. Di-hydric phenols, 417. Dihydro-anthracene, 507. Dihydro-benzenes, 349. Dihydro-benzoic acids, 445. Dihydro-carvone hydrobromide, 590. Dihydro-cinnamylidene-acetic acid, 682= Dihydro-collidine-dicarboxylic ester, 535 Dihydro-coumarone, 520. Dihydro-cymene, 578. Dihydro-methyl-pyridine, 537. Dihydro-phenazine, 551. Dihydro-phthalic acids, 466. Dihydro-pyridines, 540. Dihydro-quinoline, 546. Dihydro-terephthalic acids, 467-468. Dihydroxy-acetone, 669. Dihydroxy-anthranol, 510. Dihydroxy-anthraquinones, 509. Dihydroxy-benzenes, 417. Dihydroxy benzoic acids, 459. Dihydroxy-benzo-phenone, 486, 492. Dihydroxy-camphoric acid, 587. Dihydroxy-cinnamic acids, 464, 704 Dihydroxy-coumarine, 593. Dihydroxy-dihydro-terephthalic acid, 469. Dihydroxy-diphenyls, 473. Dihydroxy-flavone, 541. Dihydroxy-hexamethylene, 419. Dihydroxy-naphthaquinones, 503. Dihydroxy-purine, 292. Dihydroxy-stilbene, 682. Dihydroxy-tartaric acid, 261, 343. Dihydroxy-terephthalic acid, 469. Dihydroxy-toluene, 419. Di-iodo-phenol-sulphonic acid, 416. Diketo-butane, 221. Diketo-camphoric ester, 587. Diketo-hexamethylene, 419, 432, 469. Diketo-hexane, 221. Diketones, 221, 224. Di-lactic acid, 215. Dill, oil of, 575. Dimethoxy-benzidine, 474. [$6i. Dimethoxybenzyl-dimethoxyisoquinolme, Dimethyl-acetic acid, 153. Dimethyl-aceto-acetic ester, 228. Dimethyl-acrylic acid, 680. Dimethyl-allene, 669. Dimethyl-allpxan, 288. Dimethylamine, no. Dimethyl-amino-azo-benzene, 400. Dimethyl -amino-azo-benzene-sulphonic acid, 401. Dimethyl-aniline, 367, 378. Dimethyl-arsine compounds, 115, 117. Dimethyl-benzenes ; _see Xylene, 351. Dimethyl-benzoic acids, 453. Dimethyl-butane-diol, 193. 2-Dimethyl-3-butanone, 137. [583. Dimethyl-cyclobutane-dicarboxylic acid, Dimethyl-cyclohexenone, 342. Dimethyl-diamino-tolu-phenazine, 551. Dimethyl ether, 86. Dimethyl-furane, 517. Dimethyl-keten, 692. Dimethyl-ketol, 205. Dimethyl ketone, 136. Dimethyl-naphthylamines, 500. Dimethyl-nitrosamine, 108. Dimethyl-oxamic ester, 106. Dimethyl-oxamide, 106, 236. Dimethyl-parabanic acid, 287. Dimethyl-phenylamine oxide, 378. Dimethyl-phosphinic acid, 114. Dimethyl-piperidonium iodide, 540. Dimethyl-pyrazine, 550. Dimethyl-pyridines, 539. Dimethyl-pyrone, 531. Dimethyl-pyrrole, 518. Dimethyl-quinoline, 544. s-Dimethyl-succinic acids, 241. Dimethyl-thiophene, 516. Dimethyl - trimethylene - dicarboxylic acid = Caronic acid, 590. Dimethyl-uric acids, 292. Dimethyl-xanthine, 293. Dinaphthols, 502. Dinaphthyls, ^04. Dinicotinic acid, 540. Dinitro-benzenes, 360, 361. Dinitro-diphenyl, 472. Dinitro-ethane, 97. Dinitro-naphthalenes, 499. Dinitro-phenols, 414. Dinitro-toluenes, 360, 362. Dionine, 564. Dioximes, 479. Dioxindole, 522, 525. Dipalmitin, 201. Dipentene, 374. Dipentene dihydrochloride, 575, 578. Dipentene tetrabromide, 578. Diphenic acid, 474. Diphenyl, 471. Diphenyl-acetic acid, 476. Diphenyl-acetylene ; see Tolane, 478, Diphenyl-benzene, 474. Diphenyl-bromo-methane, 476. Diphenyl-butadiene, 628. Diphenyl-butyro-lactone, 240. Diphenyl-carbinol, 476. Diphenyl-carbo-di-imide, 279. Diphenyl-carboxylic acids, 473, 477. Diphenyl-ethane, 474, 476. Diphenyl-ethylene, 478. Diphenyl-glycol, 478. Diphenyl-glycollic acid, 476. Diphenyl group, 470. s-DiphenyT-hydrazme, 396. unsym.-Diphenyl-hydrazine, 398. Diphenyl-hydrazones, 221, 301. Diphenyl-keten, 692. Diphenyl ketone, 428. Diphenyl-methane, 471, 474, 476. Diphenyl-nitrosamine, 377. Diphenyl-oxide, 412. Diphenyl-quinp-methane, 692. Diphenyl-succino-nitrile, 268. Diphenyl-thio-urea, 383. Diphenyl-urea ; see Thiocarbanilide, Diphenylamine, 377. Diphenylene ketone, 477. Diphenylene-methane, 477. Diphenylene-methane oxide, 548. Diphenylene oxide, 473. Diphenyline, 473. Dipicohnic acid, 540. Dippel's oil, 535. Dipropareyl, 53. Dipropyl ketone, 133. Dipyndine, 537. Dipyridyl, 537. Disaccharoses, 299. Dissociation constants of acids, 160, 167, 447, 664. Distillation* fractional, 27. Distillation, steam, 27. Disulphides, 89. Disulphoxides, 89. Dithio-carbamic acid, 296. Dithio-carbonic acid, 295. Diurea, 284. Divalent carbon, 683. Dodecane, 30. Dodecyl alcohol, 67. Dodecylene, 43. Double bond, 44, 643. Dulcitol, 203, 307. Durene, 345, 352. IND ^ 705 Dye, 400. Dyeing, 399. Dynamic isomensm, 657. Dynamite, 201. Earth-pitch, 42. Ebulliscopic method, n. Ecg-onine, 566. Egg albumin, 599. Eicosane, 30. Eicosylene, 43. Eikonogen, 502. ElaVdic acid, 165. Elastin, 599. Electrical conductivity, 161, 663. Electrolytic oxidation, 626. Electrolytic reduction, 614. Elementary analysis, 4. Empirical Formulae, 7. Emulsin, 267, 423, 592, 672. Enzymes, 76, 77, 671. Eosin, 493. Eosin group, the, 491. Epichlorhydrin, 200. Erigeron, oil of, 575. Erucic acid, 161, 166. Erythrin, 202. Erythritol, 202. Erythro-dextrine, 319. Erythrose, 306. Erythrosin, 493. Ester alcohols, 189. Esterification, 172, 449, 677. ^ Esters, 74, 91, 172, 445. Etard reaction, the, 424, 620. Ethanal, 128. Ethanal acid, 222. Ethane, 30, 37. Ethane acid, 149. Ethane-amide, 185. Ethane-amidine, 187. Ethane di-acid, 234. Ethane-dial, 221. s-Ethane-dicarboxylic acid, 238. Ethane-nitrile, 102. Ethane-oxy-ethane, 85. Ethane-tetra-carboxylic ester (symmetr.), Ethane-thio!, 88. [495. Ethane-thiolic acid, 181. Ethane-thion-amide, 186. Ethanol, 75. Ethanolic acid, 209. Ethanoyl chloride, 179. Ethene, 48. Ethenyl-amidoxime, 188. Ethenyl-diphenyl-amidine, 187. Ether, 85. _ Ethereal oils, 567. Ethers, 83. Ethers, mixed, 84. Ethers, phenolic, 407. Ethers, simple, ( 84. Ethidene chloride, 62. Ethine, 52. Ethoxy-group, 177. Ethyl acetate, 178. Ethyl-acetchloroamide, 186. Ethyl-acetchloroimide, 186. (B480) Ethyl-acetic acid, 152. Ethyl aceto-acetate, 226. Ethyl aceto-acetate, constitution of, 227,, 643, 646, 650, 653, 654. Ethyl adipate, 232. Ethyl alcohol, 67, 75. Ethyl benzene, 345, 351. Ethyl benzoate, 445. Ethyl-benzoic acids, 443. Ethyl benzoyl-acetate, 647, 655. Ethyl bromide, 56. Ethyl butyrate, 178. Ethyl carbamate, 282. Ethyl carbonate, 279. Ethyl-cetyl-ether, 87. Ethyl chloride, 56. Ethyl chloro-carbonate, 280. Ethyl chloro-formate, 280. Ethyl collidine-dicarboxylate, 536. Ethyl cyanamide, 278. Ethyl cya.r\\Ae. = P-ropior>iiti'ile, 102. Ethyl cyanurate, 274. Ethyl diazoacetate, 212, 694. Ethyl dibenzoyl-succinates, 649. Ethyl dichloro-amine, in. Ethyl dihydrocollidine-dicarboxylate, 230. Ethyl diketo-apocamphorate, 587. Ethyl diketo-camphorate, 587. Ethyl dimethyl-aceto- acetate, 228. Ethyl dimethylacrylate, 590. Ethyl dimethyl-oxamate, 237. Ethyl dimethyl - propanetricarboxylate, Ethyl disulphide, 89. [590. Ethyl disulphoxide, 89. Ethyl ethanetricarboxylate, 239. Ethyl ether, 85. Ethyl ethyl-aceto-acetate, 228. Ethyl ethyl-keten-carboxylate, 693. Ethyl ethylsulphonate, 100. Ethyl fluoride, 60. Ethyl formate, 178. Ethyl glycollate, 209. Ethyl-glycollic acid, 209, 210. Ethyl green, 489. Ethyl hydrazine, 112. Ethyl hydrogen carbonate, 280. Ethyl hydrogen peroxide, 181. Ethyl hydrogen sulphate, 98. Ethyl hydrogen sulphite, 99. Ethyl hydrosulphide, 88. Ethyl ^-hydroxy-trimethylglutarate, 586, Ethyl-indoxyl, 523. Ethyl indoxylate, 523. Ethyl iodide, 56. Ethyl isocyanate, 273. Ethyl isocyanide, 103. Ethyl isocyanurate, 275. Ethyl isothiocyanate, 277. Ethyl lactate, 215. Ethyl lactate, molecular magnetic rota tion of, 646. Ethyl-lactic acid, 215. Ethyl malonate, 237. Ethyl mercaptan, 88. Ethyl-methyl-acetic acid, 154. Ethyl methyl-aceto-acetate, aa6. Ethyl nitrate, 93. Ethyl nitrite, 94. 706 INDEX Ethyl-nitrogen chloride, in. Ethyl-nitrolic acid, 96. Ethyl orthocarbonate, 281. Ethyl orthoformate, 142, 197. Ethyl oxalacetate, 224, 260, 655. Ethyl oxalate, 234, 236. Ethyl oxalate, reactions of, with amines, Ethyl oxalic acid, 234, 236. [106. Ethyl-oxalyl chloride, 236. Ethyl oxamate, 236. Ethyl oxamic chloride, 237. Ethyl phenylaminpcrotpnate, 543. Ethyl phloroglucinoldicarboxylate, 343, 419, 441 th , . Ethyl propanetetracarboxylate, 240. Ethyl propylbenzylphenylsilicane, 630. Ethyl propyldibenzylsilicane monosul- phonic acid, 630. Ethyl-pyridines, 538. Ethyl pyruvate, 654. Ethyl succinylosuccinate, 241, 342, 578. Ethyl sulphate, 98. Ethyl sulphide, 88. Ethyl-sulphinic acid, 100. Ethyl sulphite, 99. Ethyl sulphone, 89, 90. Ethyl-sulphonic acid, 89, 90, 99. Ethyl-sulphonic chloride, 100. Ethyl sulphoxide, 89. Ethyl tartrates, 253. Ethyl tetrahydronaphthalene - tetra-car - boxylate, 495. Ethyl thiocyanate, 276. Ethyl triazoacetate, 695. Ethyl trimethyldihydropyridine - dicar - boxylate, 535. Ethyl-urea, 285. Ethyl violets, 489. Ethylamine, no, in. Ethylamine ethyldithiocarbamate, 296. Ethylaniline, 367. Ethylene, 43, 48. Ethylene bromide, 56, 62. Ethylene-carbpxylic acid, 164. Ethylene chloride, 56, 62. .- 195- Ethylene-dicarboxylic acids, 246. Ethylene-glycol, 192. Ethylene-lactic acid, 216. Ethylene oxide, 191, 194. Ethylene-succinic acid, 238. Ethylidene-aniline, 543. Ethylidene bromide, 56, 62. Ethylidene chloride, 56, 62. Ethylidene cyanhydrin, 126, 194. Ethylidene-glycol, 192. Ethylidene-lactic acids, 213 et seq. Ethylidene-succinic acid, 241. E thylol - trimethyl - ammonium hyd roxide, Eucaine, 567. [196. Eucalyptus oil, 581. Euquinine, 560. Eurhodine, 551. Eurhodol, 552. Euxanthone, 549. Even numbers, law of, 21. Exhaustive methylation, 540, 556, 564, Extraction with ether, 28. [569, Fast red, 503. Fast yellow, 502. Fats, 158, 198, 201. Fatty acid series, 140. Fatty compounds, 24.1 Fatty compounds from benzene deriva- tives, 343. Fehlings solution, 253. Fermentation amyl-alcohol, 80. Fermentation lactic acid, 214. Fermentations, 76, 214, 666. Ferments, 76. Ferments, unorganized; see Enzymes, 76, 423, 671. Ferric chloride as an oxidizing agent, Ferropotassic oxalate, 236. [626. Ferulic acid, 464. Fibrin, 599. Fibrinogen, 599. Fire-<lamp, 34. Fittigs synthesis, 344. Flavone, 541. Flavo-purpurin, 510. Fluorane, 492. Fluoranthene, 512. Fluorene, 477. Fluorenyl alcohol, 477. Fluorescein, 493. Formaldehyde, 128. Formalin, 128. Formamide, 185. Formanilide, 382. Formhydroxamic acid, 689. Formic acid, 140, 147, 677. Formo-rhodamine, 549. Formose, 128, 312. Formula, calculation of the empirical, 7. Formulas, constitutional, 17 et seq. Formyl chloride, 684. Formyl chloride oxime, 689. Formyl-diphenylamine, 548. Fractional distillation, 27. Freezing temperature of solutions, to. Friedel-Crafts synthesis, 346, 427, 475, Fructose, 311. [481. Fruit sugar, 311. Fuchsine, 484, 485. Fuchsine-sulphurous acid, 488. Fucose, 307. Fulminic acid, 687. Fulminuric acid, 690. Fumaric acid, 242. Furaldehyde, 306, 517, 596. Furalmalonic acid, 518. Furane or Furfurane, 322, 514, 517. Furane-carboxylic acid, 518. Furo'in, 518. Furol, 517. Furylacrylic acid, 518. Fusel oil, 76, 669. Galactonic acid, 307. Galactoses, 307, 310. Galipot resin, 591. Gallein, 493. INDEX 707 Gallic acid, 460. Gallo-tannic acid, 460. Gelatin, 599. Geranial, 570. Geranic acid, 570. Geraniol, 570, 571. Gladstone- Tribe couple, 33. Gliadins, 599. Lrlobulms, 599. Gluconic acid, 219, 307. Gluco-proteins, 600. Glucose-phenylhydrazone, 309. Glucose phosphate, 668. Glucosamines, 596. Glucoses, 307, 309. Glucosides, 303, 592, 672. Glucosone, 309^"^-'-" Glutamic acid, 249, 596, 670= Glutamine, 249. Glutaric acid, 231, 240, 241. Glutaric anhydride, 530. Gluteins, 599. Glyceric acid, 218. Glyceric aldehyde, 220. Glycerides, 141, 201. Glycerine, 198. Glycerine nitrates, 200. Glycerol, 76, 198, 669. Glycerol chlorhydrins, 200. Glycerose, 306. Glyceryl-chloride, 64. Glyceryl-phosphoric acid, 199. Glyceryl-sulphuric acid, 199. Glyceryl-trinitrate, 199, 201. Glyceryl-tripalmitate, 158, 201. Glycide alcohol, 199, 200. Glycide compounds, 200. Glycine, 211. Glycocoll, 210, 211, 596. Glycocoll, salts of, 211. Glycocyamidine, 298. Glycocyamine, 298. Glycogen, 319. Glycol, 192! Glycol, ethers of, 193. Glycol bromhydrins, 191. Glycol chlorhydrins, 191, 193. Glycol iodhydrin, 191. Glycolide, 210. Glycollamide, 209, 210. Glycollic acetates, 189. Glycollic acid, 204, 205, 209. Glycollic aldehyde, 204, 220. Glycollic anhydride, 210. Glycollic di-nitrate, 193. Glycollyl chloride, 209, 210. Glycols, 188. Glycoluric acid, 285. Glycolyl-urea, 285. Glycuronic acid, 222. Glycylglycine, 597. Glyoxal, 204, 221. Glyoxalic acid, 204, 222. Glyoxalin, 530. Glyoxylic acid, 222. Grape sugar, 309. Grignarcts reagents, 72, 120 et seq., 126, 43 3S 6 . 422. 424. 4 28 - 44. 481. Guaiacol, 418. Guanidine, 278, 281, 297. Guanine, 293, 599. Guanino-amin^'ajeric acid, 596. Guldberg and nonage's law, 160, 173. Gulonic acid, 307. Guloses, 307. Gum benzoin, 444. Gums, 319. Gun cotton, 317. Guye's hypothesis, 656. Haematin, 600. Haemin, 600. Haemoglobin, 6op. Halogen derivatives of the aromatic series, Halogen derivatives of the fatty series, Halogens, detection of, 3. [54. Halogens, estimation of, 6. Haloid fatty acids, 167. Hatchett's brown, 269. Heat of combustion, 665. Helianthin, 401. Heliotrope, 429. Hemi-albumoses, 598. Hemi-mellithene, 345. Hemi-mellitic acid, 470. Hemiterpenes, 567. Heiieicosane, 30. Hentria-contane, 30. Heptane, 30. Heptoic acid, 140. Heptoses, 300. Heptyl alcohol, 67. Heptylene, 43. Heptylic aldehyde, 129. Heroin, 564. Hesperidene, 568. Hesperidin, 593. Heterocyclic compounds, 24, 322, 513. Hexabromo-benzene, 343, 357. Hexachloro-benzene, 343, 357. Hexachloro-ethane, 64. Hexa-contane, 30. Hexa-decane, 30. Hexa-decylene, 43. Hexa-diene, 53. Hexa-diine, 53. Hexahydric alcohols, 201, 203. Hexahydro-benzene, 349. Hexahydro-benzoic acid, 445. Hexahydro-isophthalic acid, 342, 469. Hexahydro-naphthalene, 497. Hexahydro-phenol, 412. Hexahydro-phthaJic acid, 466. Hexahydro-pyridine = Pfyeridine, 534. Hexahydro-terephthalic acid, 468. Hexahydro - tetrahydroxy - benzoic acid, Hexahydro-xylenes, 351. [461, Hexahydroxy-benzene, 420. Hexa-methyl-benzene, 353. Hexamethyl-para-rosanihne, 488. Hexa-methylene = Cyclo-hexane, 322. Hexa-methylene-amme, 128. Hexa-methylene carboxylic acid, 443. Hexane, 30. Hexane-pentolal, 309. 708 INDEX Hexa-phenyl-ethane, 690. Hexoses, 300, 307 et seg. Hexoses, synthesis of, 312, 319. Hexoses, 300, 307 et seg. , synthesis Hexyl alcohol, 67. Hexylene, 43. Hippuric acid, 211, 447. Histidine, 596, 599. Histories, 599. Hofmanris reaction, 107, 369. Homatropine, 565. Homocatechol, 419. Homologous series, 20. Homology, 20. Homo-phthalic acid, 547. Homoterpenylic methyl ketone, 579. Honey-stone, 470. Hydantoic acid, 285. Hydantoi'n, 285. Hydracryclic acid, 216. Hydrastine, 563. Hydratropic acid, 443, 454. Hydrazides, 398. Hydrazine, 212, 297. Hydrazines, aromatic, 397. Hydrazines, fatty, 109, in. Hydrazo-benzene, 394, 396. Hydrazo-compounds, 395. Hydrazoic acid, 212, 298. Hydrazones, aromatic, 424, 428. Hydrazones, carbohydrate, 301. Hydrazones, fatty, 127, 135. Hydriodic acid as a reducing 1 agent, 605. Hydro-benzoic acids, 445. Hydro-benzoin, 478. Hydro-carbostynl, 454. Hydro-coumaric acids, 459. Hydro-ferricyanic acid, 271. Hydro-ferrocyanic acid, 270. Hydro-isophthalic acids, 469. Hydro-paracoumaric acid, 459. Hydro-phthalic acids, 466-469. Hydro-terephthalic acids, 466. Hydrocarbons, benzene, 344. Hydrocarbons, fatty, 30. Hydrocinnamic acid, 443, 453. Hydrocotarnine, 562, 563. Hydrocyanic acid, 264, 266. Hydrocyanic acid derivatives, 100. Hydrocyano-carbpdiphenylimide, 524. Hydrogen, detection of, 3. Hydrogen, estimation of, 4. [623. Hydrogen peroxide as an oxidizing agent, Hydrolysis = Saponification, 70, 92, 159, 176, 183. Hydrolysis of disaccharoses, 312. Hydrolysis of esters, 176. Hydrolysis of ethyl acetoacetate, 226- Hydrolysis of nitriles, 101. [227. Hydromellitic acid, 470. Hydropyridines, 540. Hydroquinolines, 546. Hydroquinone = ?Mzw0/, 418. Hydroxy-acetic acid, 209. Hydroxy-acetone, 204. Hydroxy-acids, 204 et seg., 247 et seq., 456 et seq. Hydroxy aldehydes, 204. Hydroxy-anthracenes, 508. Hydroxy-anthraquinones, 509. Hydroxy-azobenzene, 397. Hydroxy-benzaldehydes, 429. Ilydroxy-benzene, 411. Hydroxy-benzoic acids, 443, 457 e Hydroxy-benzyl alcohol, 429, 593. Hydroxy-butyric acids, 207. Hydroxy-camphenilic acid lactone, 584. Hydroxy-caproic acids, 216. Hydroxy-cmoromethyl ether, Hydroxy-ethylamine, 189, 19 Hydroxy-ethyl-sulphonic aci Hydroxy-isobutyric acid, 207. Hydroxy-ketones, 204. Hydroxy-malonic acid, 247. Hydroxy-methyl-benzoic acid, 46 Hydroxy-phenyl-alanine, 459.' 28. 197. Hydroxy - phenylamino - propiomc Ilydroxy-pnenyl-ethyl alcohol, 670. Hydroxy-phenyl-propionic acid, 459. Hydroxy-propionic acids, 207, 213. Hydroxy-pyndenes, 538. Hydroxy-quinaldine, 543. Hydroxy-quinol, 408, 420. Hydroxy-quinoline, 543, 546. Hydroxy-succinic acid, 247. Hydroxy-terpane-one, 590. Hydroxy-thiotolene, 20. Hydroxy-tricarballylic acid, 262. Hydroxy-uracyl, 287. Hydroxyl groups, estimation of, 201., Hydroxylamines, in, 397, 609. Hydroxylenes, 351. Hyoscyamine, 566. Hypoxanthine, 293. /= inactive, 249. Iditol, 307. Idonic acid, 307. Idosaccharic acid, 307. Idoses, 307. Imid-azole, 530. Imides, 239. Imido-carbonic acid, 281. Imido-chlorides, 186. Imino-ethers, 185, 187, 447. Imino-formyl chloride, 268. Imino group, 104. Imino-thio-ethers, 186. , T Indamines, 434. Indican, 526. Indigo, 525. Indigo-brown, 526. Indigo-carmine, 526. Indigo-purpurin, 528. Indigo-red, 526. Indigo-sulphonic acids, 526. Indigo syntheses, 526-527. Indigo-white, 526, 527. Indirubin, 528. Indol-alanine, 596. Indole, 520, 521, 525. Indophenin, 520. Indophenols, 434. Indoxyl, 522, 52^. Indoxyl-sulphunc acid, 523, Indoxylic acid, 523. Inosite, 421. [596. acid, INDEX 709 internal viscosity, 665. Inulin, 319. Inversion, 315. Invert sugar, 315. Invertase, 77, 318. lodoacetic acid, 167. lodo-benzene, 354. lodo-propionic acids, 167, 171 lodoform, 56, 63. lodole, 518. lodonium compounds, 360. lodopropanes, 60. lodoso-benzene, 359. lodoxy-benzene, 359. lonones, 589. Irene, 589. Iron albuminate, 599. Iron and dilute acid as reducing agents, Iron peptonate, 599. [603. I rone, 589. Isatic acid, 463. I satin, 457, 463, 523, 525. Isatin-anihde, 524. Isatin chloride, 524. Isatin, constitution of, 525, 649. Isatin ethers, 524. Isatogenic acid, 524. Isethionic acid, 197. Isoamygdalin, 592. Iso-amyl-iso-valerate, 178. Iso-barbituric acid, 287. Iso-butane, 38. Isobutyl alcohol, 67, 68. Isobutyl carbinol, 80. Isobutyric acid, 153. Iso-cinchomeronic acid, 540. Iso-cinnamic acids, 454. Iso-crotonic acid, 164. Isocyanic esters, 272. Isocyanides, 102. Isocyanuric esters, 275. Isocyclic compounds, 322. Iso-dialuric acid, 288. Iso-durene, 345. Isodynamic isomerism, 657. Iso-hydrobenzo'in, 478. Isomaltose, 316, 673. Iso-melamines, 277. Isomerism, 12, 87. Isomerism, position, 133. Isomerism, side-chain, 340. Isomerism, stereo-chemical, 137, 154, 243, 2 5> 37. 3. 2 S' 34 1 - 39. 4 28 > 62 7- Isomerism. in the cyanogen group, 100- 104, 273, 684. Isomerism of fumaric and maleic acids, Isomerism of paraffins, 38. [243. Isomerism of polymethylene derivatives, 3 2 S- Isomerism of the benzene derivatives, 329 et seq. Isomers of the diazo-compounds, 389. Iso-nicotinic acid, 539. Iso-nitriles, 102, 371. Iso-nitro-methane, 96. Iso-nitroso-acetone, 136. Iso-nitroso-camphor, 586. Iso-nitroso-ketones, 136. Iso-paraffins, 32. Iso-phthalic acid, 466. Isoprene, 567, 568. Isopropyl, 39. Isopropyl-acetic acid, 153. Isopropyl alcohol, 67, 70. Isopropyl-benzene, 353. Isopropyl chloride, 60. Isopropyl iodide, 60. Isopropyl-methyl-benzene, 352. Iso-quinoline, 541, 547. Iso-rhamnose, 307. Isorosindulines, 553. Iso-saccharic acid, 260. Iso-stilbene, 478. Iso-succinic acid, 241. Iso-thio acid amides, 186. Iso-thiocyanates, 276, 371. Iso-valeric acid, 153. Isuret, 188. Japan camphor, 585. uglone, 503. umper, oil of, 581. Keratin, 599. Ketens, 691. Keto-butyric acid, 223. Keto-enolic tautomensm, 227. Keto-hexoses, 311. Keto-ketens, 692. Ketone-aldehydes, 204, Ketones, aliphatic, 131 et seq., 677, Ketones, aromatic, 427. Ketones, constitution of, 132. Ketones, mixed, 132. Ketonic acids, aromatic, 461. Ketonic acids, fatty, 204, 222, 259. Ketonic acids, fermentation of, 670. Ketonic hydrolysis, 226. Ketoses, 300, 303. Ketoximes, aliphatic, 135, 137. /=lsevo-rotatory, 249. Lactalbumin, 599. Lactam formation, 453. Lactamide, 215. Lactates, 215. /-Lactic acid, synthesis of, 661. Lactic acids, 168, 205, 213 et seq,, 669. Lactic acids, derivatives of, 215. Lactic fermentation, 214, Lactide, 215. Lactim formation, 453. Lacto-biose, 315. Lactones, 217. Lactose, 315. Lactyl chloride, 215. Lactyl-urea, 285. Lactylic acid or Lactic anhydride, 215. Laevo-coniine, 557. Lffivo-limonene, 75. Lasvo-tartaric acid, 249. Laevulic acid, 223, 230. Laevulose, 311. Lakes, 400, 509. Laudanosine, 561. Laurie acid, 140, 157. 710 INDEX Lead, sugar of, 151. Lead, tetraethyl, 120. Lead, tetramethyl, 120. Lead, trimethyl hydroxide, 120. Lead acetates, 151. Lead mercaptan, 89. Lead peroxide as an oxidizing agent, 622, Leather, 460. Le Bel-van t ffoff hypothesis, 154. Leucaniline, 484. Leucaurine, 490. Leucine, 216, 596, 669. Leuco-bases, 482. Leuco-compounds, 399, 482. Leuco-malachite green, 483. Leuco-rosolic acid, 490. Lichenin, 319. Ltebermanris reaction, 377, 409. Light blue, 489. Light green, 489. Lignoceric acid, 140. Ligroi'n, 42. Limonene nitroso-chloride, 575, 578. Limonene tetrabromide, 575, 578. Limonenes, 574, 575. Linalool, 572. Lipase, 668, 672. Liponic acid, 559. Liver starch, 319. Lotusin, 592. Lupetidines, 540. Luteolin, 541. Lutidines, 539. Lutidimc acid, 540. Lysine, 219, 596. Lyxose, 306. Madder root, 509. Magenta, 484, 487. Magnetic susceptibility, 665. Malachite green, 484. Malamic acid, 248. Malamide, 248. Maleic acid, 242. Malic acid, 247. Malonic acid, 231, 237, 241. Malonic anhydride, 238. Malonic ester, 237. Malonic ester synthesis, 237. " Malonyl", 233. Malonyl-urea, 288. Malt sugar, 315. Maltase, 78, 318, 671, 672. Maltobiose, 315. Maltose, 315, 673. Mandelic acid, 443, 461. Manganese dioxide as an oxidizing agent, Mannide, 203. [623. Mannitan, 203. Mannitol, 203, 307. Manno-heptose, 660. Manno-nonose, 660. Manno-octose, 660. Manno-saccharic acid, 260, 307. Mannonic acid, 220, 307. Mannose-phenyl-hydrazone, 310. Mannoses, 307, 310. Margaric acid, 140. Marsh -gas, 34. Martins' yellow, 502. Mauve, 552, 553. Meconme, 562. Melamine, 277. Melene, 43, 49. Melibiose, 316. Melissic acid, 140. Melissic alcohol, 81. Melissic palmitate, 158, 178. Melitriose, 316. Mellitene, 353. Mellitic acid, 34^, 470. Mellophanic acid, 470. Melting-point, 25, 638. Melting-point curves, 638. Melting-point curves of racemic com- pounds, 258. Mendius reaction, 106, 606. Menthadienes, 574. Menthane, 574. Menthene, 578. Menthol, 578. Menthone, 578. Menthone-semicarbazone, 579. Menthyl benzoyl-formate, 661. Menthyl lactates, 660. Menthyl phenyl-methyl-glycollate, 661. Menthyl pyruvate, 660. Mercaptans, 88. Mercaptides, 88. Mercaptol, 136. Mercurialin, no. Mercuric cyanide, 269. Mercuric 'formate, 149. Mercuric mercaptide, 89. Mercuric oxide as an oxidizing agent, 626. Mercurous formate, 149. Mercurous thiocyanate, 276. Mercury ethyl, 120. Mercury fulminate, 688. Mercury methyl, 120. Merpquinine, 559. Mesidme, 367. Mesityl oxide, 135, 137. Mesitylene,-i3$. 339, 342, 345, 351. Mesitylenic acid, 443, 453. Meso-tartaric acid, 246, 249, 254. Mesoxalic acid, 199, 260. Mesoxalyl-urea, 288. Meta-compounds, 333, 337. Metacymene, 345. Metaldehyde, 129. Metallic cyanides, 268, 684-687. Metamerism, 87. Metanilic acid, 406. Metaproteins, 600. Meta-styrene, 353. Methacrylic acid, 165. Methanal, 128. Methane, 30, 34. Methane acid, 147. Methane-amide, 185. Methanol, 74. Methene, 47. Methoxy-benzaldehyde, 429. Methoxy-benzyl alcohol, 429. Methoxy-group, 177. INDEX 711 Methoxy-hydrqxy-benzaldehyde, 429. Methoxy-pyridine, 538. Methoxy-quinoline-carboxylic acid, 559. Methyl-acetanilide, 382. Methyl-acridine, 548. Methyl alcohol, 67, 74. Methyl-alloxan, 288. Methyl -allyl - phenyl -benzyl -ammonium iodide, 631. Methyl-amine, no. Methyl-aniline, 367, 377. Methyl-arbutin, 593. Methyl-arsenic compounds, 115 et seq. Methyl-arsine chlorides, 115 et seq. Methyl-benzene; see Toluene, 340, 345, Methyl-benzimido-azole, 380. [350. Methyl benzoate, 445. Methyl-benzqic acids, 443, 449, 452. Methyl bromide, 56. 2-Methyl-butane acid, 154. 3-Methyl-butane acid, 153. Methyl carbonate, 280. Methyl-carbqstyril, 543. Methyl chloride, 56, 59. Methyl-chloroform, 63. Methyl-cyanamide, 278. Methyl-cyanide, 102. Methyl dimethyl-amino-acetate, 212. Methyl ether, 86. Methyl-ethyl-acetic acid, 154. Methyl-ethyl-aceto-acetic ester, 228. Methyl-ethyl-aniline oxide, 633. Methyl-ethyl-benzenes, 345. Methyl-ethyl-carbinol, 126. Methyl-eth}'l ether, 84. Methyl-ethyl ketone, i-;?. [628. Methyl-cthyl-phenacyl-sulphine bromide, Methyl-ethyl-propyl-iso-butyl-ammonium chloride, 632. Methyl-ethyi-w-propyl-tin ?-camphor sul- phonate, 629. Methyl-ethyl-propyl-tin iodide, 629. Methyl-ethyl-selenetine bromide, 628. Methyl-ethyl sulphide, 89. Methyl-ethyl sulphone, 89. Methyl-ethyl-thetine bromide, 628. Methyl - ethyl - thetine d- camphor - sul - phonate, 628. Methyl-furane, 517. Methyl galactoside, 311. Methyl glucosides, 310, 592, 672. Methyl-glycocoll, 212. Methyl-glyoxal, 204. Methyl-green, 480. Methyl-heptenone, 571. Methyl-hydantoin, 285. Methyl-hydrazine, 112. Methyl-indole, 521. Methyl iodide, 56. Methyl-isatin, 524, 649. Methyl isocyanide, 103. Methyl-isopropyl-benzene, 352. Methyl-isoprqpyl-hydroxy-benzenes, 417. Methyl-iso-thiacetanilide, 187. Methyl isothiocyanate, 277. Methyl-malonic acid, 233, 241. Methyl-morphmethine, 564. Methyl-morphol, 564. Methyl-naphthylamines, 500. Methyl-nitramine, 109. Methyl nitrate, 93. Methyl nitrite, 94. Methyl-nitrolic acid, 96, 689. Methyl-orange, 401. Methyl oxalate, 236. Methyl-oxamic ester, 106. Methyl-parabanic acid, 287. Methyl-phenyl-fr uctosazone, 311. Methyl-phosphonic acid, 114. Methyl-piperidines, 540. Methyl-propane acid, 153. Methyl-propane di-acid, 241. 2-Methyl-2-propene-i-acid, 165. Methyl-propyl-benzenes, 352. Methyl-pyridines, 538. Methyl-pyridone, 538. Methyl-pyridonium iodide, 534. Methyl-pyrrolidine, 569. Methyl-quinolines, 543, 546. Methyl-succinic acid, "241. Methyl sulphate, 98. Methyl-sulphonic acid, 99. Methyl-tertiary-butyl ketone, 137. Methyl-uracyl, 230, 287. Methyl-urea, 285. Methyl-uric acids, 292. Methyl violets, 488. Methyladipic acid, 578. Methylal, 128. Methylamine platinichloride, 107. Methylated rosanilines, 488. Methylene, 47. Methylene blue, 554. Methylene bromide, 56, 61. Methylene chloride, 56, 61. Methylene-glycol, 192. Methylene iodide, 56, 61. Methylene-quinones, 434. Methylene violet, 553. Micro-organisms for resolving racemic compounds, 256. Milk sugar, 315. Millon's reagent, 594. Mineral lubricating oils, 42. Mint camphor, 578. Miricyl alcohol, 81. Mixed amines, 106. Mixed anhydrides, 181. Mixed ethers, 84. Mixed ketones, 132. Mixed sulphides, 89. Molasses, 314. Molecular magnetic rotation, 644. Molecular rearrangements, 108, 137, 163, 377. 393. 395- 39?. 4". 5<>i- Molecular refraction, 641. Molecular rotation, 656. Molecular volume, 639. Molecular weight, determination of, 8-ia Monoformin, 148. Monohydric alcohols, 65. Monohydroxy fatty acids, 205. Mononitrin, 200. Monopalmitin, 201. Monosaccharoses, 299. Mordants, 400. 712 INDEX Morphine, 564. Morpholine, 531. Moss starch, 319. Mucic acid, 259, 307. Mucins, 600. Multi-rotation, 309. Murexide, 289. Muscarine, 196. Musk, artificial, 362. Mustard oils, 275, 371". Mutarotation, 309, 315, 658. Myosin, 277, 599. Mynstic acid, 140, 157. Myronic acid, 593. Myrosin, 275, 593. Naphthalene, 471, 494. Naphthalene-carboxylic acids, 504. Naphthalene-dicarboxylic acids, 504. Naphthalene dichloride, 497. Naphthalene-sulphonic acids, 501. Naphthalene tetrachloride, 497. Naphthalic acid, 504. Naphthaquinones, 503. Naphthazarine, 503. Naphthazines, 550. Naphthenes, 41. Naphthionic acid, 501. Naphtho-acridines, 548. Naphtho-phen-oxazine, 550. Naphthoic acids, 503. Naphthol dyes, 502. Naphthol-sulphonic acids, 502. Naphthol yellow, 502. Naphthols, 495, 501. Naphthylamine-sulphonic acids, 501. Naphthylamines, 499. Narcotine, 561. Nerol, 572. Nerolin, 502. Neurine, 196. Neutral esters, 91, 97. Neutral red, 552. Neutral violet, 552. Nicholson's blue, 489. Nickel powder and hydrogen as a reduc- ing- agent, 610. Nicotine, 557. JJJf . nic acid ' 539. 557- Nile blue, 554. Nitracetanilides, 374. Nitramines, 109. Nitranilic acid,- 433. Nitranilines, 375, 652. Nitric acid, constitution, 95. Nitric acid as an oxidizing agent, 621. Nitriles, aliphatic, 101. Nitriles, aromatic, 438. Nitriles, constitution of, 103. Nitro-alizarin, 510. Nitro-benzaldehydes, 426, 521. Nitro-benzene, 360, 361. Nitro-benzene, electrolytic reduction of, 615. Nitro-benzene as an oxidizing agent, 626. Nitro-benzene-sulphonic acids, 405. Nitro-benzoic acids, 446, 449. Nitro-benzoyl-formic acid, 462, 523. Nitro - benzyl - phenyl-nitrosamine, reduc tion of, 604. Nitro-camphors, 587, 657. Nitro-cinnamenes, 362. Nitro-cinnamic acid dibromide, 453. Nitro-cinnamic acids, 455. Nitro-decane, 95. Nitro-derivatives, aliphatic, 94. Nitro-derivatives, aromatic, 359. Nitro-dimethyl-aniline, 378. Nitro-diphenyl-amines, 377. Nitro-ethane, 94. Nitro-glycerine, 201. Nitro-guanidine, 297. Nitro-mesitylene, 360. Nitro-methane, 94. Nitro-naphthalenes, 499. Nitro-naphthols, 502. Nitro-naphthylamines, 500. Nitro-phenols, 414, 653. Nitro-phenols, salts of, 414, 653. Nitro-phenyl-acetic acid, 524. Nitro-phenyl-acetylene, 363. Nitro-phenyl-glyoxylic acid, 523. Nitro-phenyl-hydrazine, 399. Nitro-phenyl-lactyl-methyl ketone, 527. Nitro-phenyl-propiolic acid, 456, 524. Nitro-prussic acid, 272. Nitro-styrenes, 362. Nitro- tartaric acid, 253. Nitro-thiophene, 519. Nitro-toluenes, 360, 362. Nitro-uracyl, 287. Nitro-uracyl-carboxylic acid ; 287. Nitro-xylenes, 360. Nitroform, 97. Nitrogen, detection of, 3. Nitrogen, estimation ofT 5. Nitrogen, quinquevalent, 105, 379, 631. Nitrogen bases of the alkyl radicals, 104. Nitrogen isomerism, 138, 428, 631. Nitrolamines, 573. Nitrolic acids, 96. Nitrosamines, 108, 376. Nitrosamines of aromatic bases, 376.' Nitrosates of terpenes, 573. Nitrosites of terpenes, 573. Nitroso-benzene, 365. Nitroso-chlorides of terpenes, 573. Nitroso-diethyl-aniline, 379. Njtroso-dimethyl-aniline, 378. Nitroso-indole, 521. Nitroso-indoxyl, 523. Nitroso-limonenes, 575. Nitroso-phenol, 378, 414, 432. Nitrous acid, constitution of, 95. Nomenclature, international, 40. Nomenclature of the alcohols, 73. Nomenclature of the hydrocarbons, 39 Nonane, 30. \et seg. Nondecyhc acid, 140. Nonoses, 300. Nonyl alcohol, 67. Nonylene, 43. Nonylic acid, 140. Normal esters, 91, 97. Normal salts, 144. Norpinic acid, 583. INDEX 713 Nucleic acid, 599. Nucleo-proteins, 599. o = ortho; see Ortho-compounds. Octa-acetyl derivatives of sugars, 314. Octa-decyler.e, 43. Octane, 30. Octoses, 300. Octyl alcohol, 67. Octylamine, no, Octylene, 43. Octylic acid ; see Caprylic acid, 175. CEnanthol, 129. Oil of bitter almonds, 266, 423. Oil of the Dutch chemists, 44. Oils, ethereal, 567. Oils and fats, 158. Olefine bond, 44. Olefines, 42. Olefines, constitution of, 46. Olefines, formation of, 45. Oleic acid, 158, 161, 165. Oleic series of acids, 162. Olein, 158. Olive oil, 158. Open chains, 20, 321. Opianic acid, 562. Opium bases, 560, 564. Optical activity, 154, 656, 694. Optically active compounds, their pre- paration by means of ferments, 256. Orange, oil of, 568. Orange II, 502. Orcinol, 408, 419. Organo-magnesium compounds, 121, 403. Organp-metallic compounds, 1 18, 403. Ornithine, 219, 596. Ortho-acetic ester, 197. Ortho-acids, 142. Ortho-acids, derivatives of, 178. Ortho-carbonic ester, 202, 281; Ortho-compounds, 333; 337. Ortho-formic acid, 197. Ortho-quinones, 430. Osazones, 222, 301. Osones, 304. Oxal-acetic acid, 260, 670. Oxalic acid, 204, 231, 234, 241. Oxalic ester; see Ethyl oxalate. Oxaluric acid, 286, 287. "Oxalyl", 233. Oxalyl chloride, 234. Oxalyl-urea ; see Parabanic acid, 286, Oxamethane, 237. [287. Oxamic acid, 234, 236. Oxamide, 234, 236. Oxanilic acid, 382. Oxanilide, 382. Oxazole, 530. Oxidases, 671. Oxidation, 616. Oxidation, catalytic, 674. Oxidation, effects of conditions on, 617. Oxidation, electrolytic, 626. Oxidation with acidified permanganate, 619. [618. Oxidation with alkaline permanganate, Oxidation with chromic anhydride, 620. Oxidation with chromyl chloride, 620. Oxidation with dichromate and acid, 620. Oxidation with neutral permanganate, Oxidation with nitric acid, 621. [619. Oxidation with oxygen, 623. Oxidation with ozone, 624. Oxidation with peroxides, 622. Oxidation with sulphuric acid, 622. Oximes, 127, 135, 137/301, 428. Oximide, 237. Oxindole, 452, 522, 525. Oxonium salts, 532. Oxozonides, 624. Oxy-carbanil, constitution of, 650. Oxy-hasmoglobin, 600. Oxy-methylene-camphor, 655. Oxy-proline, 596. Oxy-purine, 293. Oxy-uvitic acid, 230. Oxygen, estimation of, 6. Ozokerite, 42. Ozone as an oxidizing agent, 624. Ozonides, 624. /=para; see Para-compound& Palatin black, 503. Palmitic acid, 140, 157, 161. Palmitin, 158. Palmito-nitrile, 102. Papaveraldine, 560. Papaverine, 560. Papaveroline, 560. Para-aldehyde, 129. Para-anthracene, 507. Para-compounds, 333, 337. Para-cyanogen, 265. Para-formaldehyde, 128. Para-fuchsine, 486. Para-lactic acid, 2i.<;. Para-leucaniline, 484, 485, Para-quinones, 430. Para-rosaniline, 485. Para-tartaric acid; see Racemie acid, 24^,. Parabanic -acid, 286, 287. Paraffin, liquid, 42. Paraffin wax, 42. Paraffins, 31. Paraffins, constitution of, 38. Paraffins, formation of, 33. Paraurazine, 284. Paroxazine, 549. Partial valencies, 683. Partition coefficient, 28. ' Patent blue, 480. Pelargonic acid, 165. Penta-chlor-aniline, 374. Penta-decylene, 43. Penta-decylic acid, 140. Penta-hydric alcohols, 201, 202. Penta-hydroxy-flavone, 541. Penta-methylene, 322. Penta-methylene-diamine, 196, 535, 598. Penta-phenyl-ethane, 690. Penta-triacontane, 30. Pentacetyl-galactose, 311. Pentacetyl-glucose, 303, 309. Pentane acid, 153. . Pentane di-acid, 240. 714 Pentanes, 30, 38. Pentanone di-acid, 260. Pentoses, 300, 306. Peppermint, oil or, 570. Pepsin, 598. Peptones, 598, 600 Per-acid salts, 144. Perbenzoic acid, 440, Perchlor-ether, 86. Perchloro-ethane, 64. " Peri "-position, 490- Perkins synthesis, 425, 441- . . Permanganate as an oxidizing ag_ent, Peronine, 564. INDEX A _ oxidizing agents, 622. Perozonides, 624. Petroleum, 41. Petroleum ether, 42. Phaseolunatin, 592. Phellandrene, 577- . Q Phellandrene derivatives, 578. "Phenacetine", 415- Phenacyl bromide, 427. Phenanthra-qumone, 512. Phenanthrene, 510. Phenanthrene-/3-carboxyhc acid, 5" Phenanthrene picrate, 511. Phenanthrene-qumol, 512 Phenanthrol, 512. Phenates, 407. Phenazine, 549, 55 1 - Phenetedines, 415- Phenetole, 412. Pheno-safranine, 552. Phenocoll, 415. Phenol, 406. 4, Phenol, esters of, 407. Phenol, ethers of, 407. . Phenol-methyl ether; vxAnisok, 407 Phenol-phthaleln, 492. Phenol-phthaline, 40?. Phenol-sulphonic acids, 416. Phenolic acids, aromatic, 457. Phenols, 407. Phenoxazine, 554. Phenoxides, 407. Phenthiazine, 550. Phenyl acetate, 413. Phenyl-acetic acid, 443, 45^- Phenyl-acetylene, 353. Phenyl-acridine, 548. ., ~ Phenyl-acridonium hydroxide, 665. Phenyl-alanine, 453, S9&. 6 7- . .,., Phenyl-allyLdimethyl-ammonium iodide, Phenyl-amine, 372. Phenyl-amino-acetic acid, 452. Phenyl-amino-propionic acids, 453, 59- Phenyl-benzoic acid, 477. Phenyl -benzyl -methyl -ethyl -ammonium iodide, 632. Phenyl-carbimide, 383. Phenyl-carbinol, 421. Phenyl-chlpracetic acid, 452. a-Phenyl-cinnamo-nitrile, 267. Phenyl-cyanide ; see Bcnzomtrile, 447- Phenyl-dibromo-propionic acid, 454. Phenyl-dimethyl-pyrazolone, 230, 529. Phenyl - dipropyl - methyl - ar ""-y:-"V Phenyl-disulphide, 413. [iodide, 632. Phenyl ether, 412. Phenyl-ethyl-alcohols, 422, 670. Phenyl-ethyl ether, 412. Phenyl-ethylene, 353. Phenyl-glucosazone, 309. Phenyl-glycerol, 422. Phenyl-glycine, 383. Phenyl-glycocoll, 383, 527. Phenyl-glycocoll-o-carboxyhc acid, 527. Phenyl-glycollic acid, 460. Phenyl-glyoxylic acid, 427, 462. Phenyl-hydrazme, 398. Phenyl-hydrazones, 127, 135, 424. 427.428. Phenyl hydrogen sulphate, 412. Phenyl-hydrosulphide, 413. Phenyl-hydroxylamine, 394, 397- Phenyl-hydroxy-propiomc acid, 462. Phenyl-imi no-butyric acid, 383. Phenyl-iodide'dichloride, 358. Phenyl-isocrotonic acid, 456, 490. Phenyl-isocyanate, 383. Phenyl-isothiocyanate, 383. Phenyl magnesium bromide, 403. fnenyi-meLu>i-cu.v ^~ Phenyl-methyl hydrazme, 398. Phenyl-methyl ketone, 427. Phenyl-methyl-pyrazolone, 230, 529- Phenyl-naphthalene, 504. Phenyl-naphthylammes, 500. Phenyl-nitramine, 389. Phenyl-nitro-methane, 363. Phenyl-phenazomum chloride, 553. Pheriyl-phosphine, 403- Phenyl-phosphinic acid, 403. Phenyl-propiolic acid, 443, 4S b - Phenyl-propionic acids, 453. Phenyl radical, 329. Phenyl salicylate, 45- Phenyl-salicylic acid, 458. Phenyl sulphide, 413- Phenyl-sulphonamic acid, 405. Phenyl sulphone, 413- Phenvl-^-tolyl-anti-ketoxime, 429. Phenyl-J-tolyl-syn-ketoxime, 4 29. Phenylene diammes, 380. Phloretic acid, 593. Phloretin, 593. Phloridzin, 593- Phloroglucinol, 343- ** 4 2 - 593- Phloroglucinol-di-carboxyhc ester, 441- PWorollucinol-hexa-methyl ether 42C Phloroglucinol-mono-meth>-l ether, 542, Phlorollucinol-trimethyl ether, 420. Phloroglucinol-trioxime, 420. Phloxin, 493. Phorone, 135. i37 6l 3- Phosgene, 280. < Phosphenyl chloride, 403. Phosphine, 548. Phosphine-oxides, 113. Phosphines, 113 et seq. Phosphinic acids, 114. Phosphino-benzene, 403. INDEX 715 Phospho-benzene, 403. Phospho-proteins, 599. Phosphonic acids, 1 14. Phosphonium bases, 113, 114. Phosphoric esters, too. Phosphorous esters, 100. Phosphorus, detection of, 4. Phosphorus, estimation of, 6. Phosphorus compounds, aromatic, 402. Phthalei'ns, 491. Phthalic acids, 464, 466. Phthalic anhydride, 465. Phthalide, 462, 466. Phthalimide, 465. Phthalines, 492. Phthalo-phenone, 465, 491. Phthalyl chloride, 465. Physical properties of organic compounds, Picene, 512. [24 et seq., 635 et seq. Picolines, 538. Picolinic acid, 539. Picramide, 375. Picric acid, 414. Picryl chloride, 362, 415 Pimaric acid, 591. Pimelic acid, 231, 344. Pinacoline, 137, 193. Pinacone, 193. Pinene, 581. Pinene dibromide, 582. Pinene glycol, 582. Pinene hydrochloride, 582. Pinene nitroso-chloride, 582. Pinic acid, 583. Pinole, 582,. Pinonic acid, 583. Pipecplines, 540. Piperic acid, 464, 540. Piperidei'ns, 540. Piperidine, 196, 531, 534, 535, 540. Piperidme, constitution of, 535. Piperine, 464, 540. Piperonal, 429. Piperpnylic acid, 460. Pivalic acid, 157. Platinichlorides, 107, 370. Polyamines, aromatic, 380. Polybasic acids, 261. Polymerism, 12. Polymerization of acetylenes, 51, 341. Polymerization of aldehydes, 126. Polymerization of nitriles, 102. Polymerization of defines, 45. Polymethylene derivatives, 322 et seq. Polypeptides, 597, 600, 672. Polysaccharoses, 299, 316. Polyterpenes, 567. Ponceau, 2 R, 503. Populin, 593. Position isomerism, 87. Potassium acetates, 151. Potassium antimonyl-tartrate, 253. Potassium carboxide, 343. Potassium cyanate, 273. Potassium cyanide, 269. Potassium diazobenzene oxide, 390. Potassium ethide, 119. Potassium ethyl-carbonate, 280. Potassium ferricyanide, 271. Potassium ferricyanide as an oxidizing 1 agent, 626. Potassium ferri-ferrocyanide, 271. Potassium ferrocyanide, 270. Potassium ferro-ferrocyariide, 271. Potassium formate, 148. Potassium indoxyl-sulphate, 523. Potassium methide, 119. Potassium methoxide = potassium methy- Potassium myronate, 277. [late, 75. Potassium persulphate as an oxidizing Potassium pyrrole, 518. [agent, 626. Potassium thiocyanate, 275. Potassium xanthate, 295. Prehnitic acid, 470. [146. Primary, secondary, and tertiary acids, Primary, secondary, and tertiary alcohols, 68-70, 72, 97. [104 et seq. Primary, secondary, and tertiary amines, Primary, secondary, and tertiary di- amines, 195. Primary, secondary, and tertiary nitro- compounds, 96. [phines, 113. Primary, secondary, and tertiary phos- Primary, secondary, tertiary, and qua- ternary hydrazines, 112. Prism formula of benzene, 336. Proline, 596. Propadiene, 53. Propane, 30, 38. Propane di-acid, 237. Propane-diol acid, 218. Propanc-diols, 192. Propane-nitrile, 102. Propane-2-pl-i-acid, 214. Propane- tricarboxylic acid, 261. Propane-triol, 198. Propanol, 80. Propanol di-acid, 247. Propanone, 136. Propargyl alcohol, 82. Propargylic acid, 166. Propenal, 130. Propene, 48. Propene acid, 164. Propine, 53. Propmol, 82. Propio-nitrile, 102. Propiolic acid, 166. Propionic acid, 140, 152, Propionyl, 14^7. Propyl bromides, 56, Co. Propyl carbonate, z''o. Propyl chlorides, 56, Co. Propyl iodides, 56, 60. Propyl-acetic acid, 153. Propyl-aceto-acetic ester, ziQ Propyl-alcohols, 67, o. Propyl- aldehyde, 129. Propyl-amines, no. Propyl-benzenes, 345, 352. Propyl-methyl-benzenes, 352. Propyl-piperidincs, 538. Propyl-pseudo-nitrol, 96. Propyl-pyridines, 538. Propylene, 43, 48. Propylene glycols, 192. 716 INDEX Protamines, 599. Proteins, 599. Proteoses, 600. Protocatechuic acid, 459, 542. Protocatechuic aldehyde, 429. Prussian blues, 271. Prussic acid, 266. Pseudo-acids, 96, 364, 491, 665. Pseudo-bases, 487. Pseudo-cumene, 345, 352. Pseudo-cumenol, 408. Pseudo-cumidine, 367. Pseudo-indoxyl. 523. Pseudo-methylisatin, 524. Pseudo-nitrols, 97. Pseudo-phenols, 434. Pseudo-uric acid, 291. Ptoma'mes, 196, 598. Pulegone, 570, 579. Purine, 290. Purine group, 290 et sea. Purpuric acid, 289. . Purpurin, 510. Putrescine, 195, 598. Pyrazine, 531, 550. Pyrazole, 528, 695. Pyrazolidine, 528. Pyrazoline, 528, 695. Pyrazolone, 528. Pyrene, 512. Pyridazine, 531, 550. Pyridine, 322, 531, 533. Pyndine-carboxylic acids, 539, 545, 560. Pyridine derivatives, 536 et scq. Pyridyl-methyl-pyrrole, 558. Pyridyl-methyl-pyrrolidine, 557. Pyridyl-pyrrole, 558. Pyrimidine, 531, 550. Pyro-mellitic acid, 470. Pyro-mucic acid, 518. Pyro-racemic acid, 223, 225. Pyro-tartaric acid, 241. Pyrocatechin = CafecAp/, 417. Pyrogallol Pyrogallic acid, 408, 419. Pyrogallol-carboxylic acid, 460. Pyrogallol-dim,ethyl ether, 420. Pyrohgneous acid, 150. Pyrone, 531. Pyrone-dicarboxylic acid, 533. Pyronine, 492, 547. Pyroxylme, 317. Pyrrole, 322, 515, 518. Pyrrolidine, 519. Pyrrolidine-carboxylic acid, 596. Pyrroline, 518. Pyruvic acid, 204, 225, 670. Pyruvic acid phenyl-hydrazone, 226. Qualitative analysis, 2. Quantitative analysis, 4. Quaternary ammonium bases, 104, 379. juercitin, 541. Juercitol, 421. Juinaldine, 543, 544, 546. Jumhydrpne, 431. )uinic acid, 461, 559. nnine, 558. linitol, 419. >uinol, 408, 418. )uinol-dicarboxylic acid, 469. Juinoline, 541, 542. )uinoline carboxylic acids, 546. Juinoline decahydride, 546. Juinoline yellow, 546. )uinolinic acid, 536, 540. >uinolinium salts, 546. juinone chlorimide, 434. Juinone dichlorimide, 434. Juinone-aniles, 434. Juinone-dioxime, 432. Juinone-oxime, 434. Juinones, 381, 430, 503, 508, 512, 652. Juinonoid formulae, 486. >uinovose, 307. Quinoxaline, 551. Racemic acid, 249, 253. Racemic compounds, 253, 258. "Racemic" modification, 156. Racemisation, 257, 629. Radicals, 22. Raflfinose, 316, 671. Red prussiate of potash, 271. "Reduced" benzene derivatives, 348, 466 Reduction, 601. '[et seq. Reduction, catalytic, 610. Reduction, electrolytic, 614. Reduction in acid solution, 601. Reduction in alkaline solution, 606. Reduction in neutral solution, 608. Reduction with ethyl alcohol, 609. Reduction with hydrogen sulphide, 610. Reduction with metals, 609. , Reduction with nascent hydrogen, 601. Reduction with sodium ethoxide, 609. Reduction with sodium hyposulphite, 610 Reduction with sodium stannite, 609. Reduction with sulphurous acid, 610. Reformatsky's reaction, 263. Refraction, molecular, 641, 693. Resin acids, 591. Resin soaps, 591. Resins, 591. Resolution of ^-lactic acid, 215. Resolution of f-mandelic acid, 462. Resolution of racemic compounds, 253. Resorcin yellow, 401. Resorcinol, 408, 418. Retene, 512. Rhamnazin, 541. Rhamnetin, 541. Rhamnitol, 203. Rhamnose, 306. Rhodamines, 493. Rhodeose, 307. Ribose, 306. Rochelle salt, 253. Rosaniline, 485. Rosaniline group, 484. Rosaniline salts, 485. Rosinaulines, 553. Rosolic acid, 490. Sabinene, 585. Saccharate, strontium, 314. Saccharic acid, 259, 307. INDEX 717 Saccharjmetry, 315. Saccharine, 452. Saccharo-biose, 314. Saccharomyces, 76, 80. Safranines, 552-553. Sage, oil of, 581. Salicin, 592. Salicyl-aldehyde, 429. Salicylic acid, 443, 457. Saligenin, 429, 593. Salmine, 596. Salol, 458. Salophene, 458. Saloquinine, 560. Salt out, 159, 594. Salts or fatty acids, 144. Salts of sorrel, 236. Sandmeyer's reaction, 388. Saponification, 70, 158. Sarcine, 293. Sarco-lactic acid, 215. Sarcosine, 212. Saturated hydrocarbons, 30. Saturation isomerism, 133. Scarlet, Biebrich, 503. Schiff's bases, 371, 425. Schijfs reagent, 488. Scleroproteins, 599. Secondary alcohols, 69 et seq., 126. Secondary arsines, 1 16. Secondary butyl iodide, 60. Secondary nitro-compounds, 90. Seignette salt, 253. Selenium compounds, 91. Semicarbazide, 136. Semicarbazones, 136. Semicylic bonds, 574, 694. Serine, 218, 596. Serum albumin, 599. Sesqui-terpenes, 567. Shellac, 591. Side-chain isomerism, 340. "Side chains", 347. Silico-nonane, 1 18. Silico-nonyl alcohol, 118. Silicon compounds, 118, 629. Silk, artificial, 318. Silver formate, 149. Silver fulminate, 688. Silver oxide as an oxidizing agent, 626. Simple ethers, 84. Simple ketones, 132. Sinigrin, 593. Skatole, 522. Skatolglycocoll, $96. Skraup's synthesis, 542. Slow neutralization, 665. Soaps, 158 et seq. Sobrerol, 582. Sobrerythritol, 583. Sodio-aceto-acetic ester, 228. Sodio-malonic ester, 237. Sodium acetate, 151. [608. Sodium amalgam as reducing agent, 605, Sodium as a reducing agent, 606. Sodium ethide, 1 19. Sodium ethoxide, 79. Sodium formate, 147. Sodium glycolls, 191. Sodium methide, 119. Sodium nitro-prusside, 270. Solanine bases, 565. Solubility, 24. Soluble starch, 319. Sorbic acid, 166, 682. Sorbitols, 203, 307. Sorbose, 312. Sozo-iodol, 414. Sozolic acid, 416. Specific gravity, 25, 639. Specific refractive power, 641. Specific rotatory power, 656. Specific volume, 25. Spermaceti, 158. Spirit blue, 489. Spirits of wine, 75. [322. Stability of polymethylene derivatives, Stannous chloride as reducing agent, 603. Starch, 319. Starch, animal, 319. Starch, soluble, 319. Steam distillation, 27. Stearic acid, 140, 157, 161, 198. Stearin, 158. Stearin candles, 158. Stereochemistry of carbon, 154, 250, 307, 325, 340, 634. Stereochemistry of cobalt, 634. Stereochemistry of nitrogen, 138, 428, 631. Stereochemistry of phosphorus, 634. Stereochemistry of selenion, 628. Stereochemistry of silicon, 629. Stereochemistry of sulphur, 628. Stereochemistry of tin, 629. Stereoisomerism, 154. [340. Stereoisomerism of benzene derivatives, Stereoisomerism of glucoses, &c., 307. Stereoisomerism of oximes, 138, 428, 635. Stereoisomerism of polymethylene deriva- tives, 325. Stereoisomerism of tartaric acids, 250. Stereoisomerism of valeric acids, &c., 154. Steric retardation or hindrance, 175, 449, Stilbene, 471, 478. [651. Stilbene dibromide, 478. Storax, 353, 423, 454. Strychnine, 565. Strychnine bases, 565. Sturine, 599. Styphnic acid, 418. Styrene, 353. Suberic acid, 231. "Substantive dyes", 473, 478. Substituted benzoic acids, 448. Substitution, 31, 55. Substitution, inverse, 45. Substitution, laws governing, 448. Succinamic acid, 239. Succinamide, 239. Succinic acid, 231, 238, 241, 669, 670, Succinic anhydride, 240. Succinimide, 234, 239. Succinpnitrile, 194. "Succinyl", 233. Succinyl chloride, 240. Succinylosuccinic acid, 469. 718 INDEX Sucrase, 671. Sucrose, 314. Sugars, the, 300 et seq. Sulphanilic acid, 405. Sulphides, 88, 90. Sulphinic acids, aromatic, 405. Sulphinic acids, fatty, 99. Sulpho-acetic acid, 171. Sulpho-benzimide, 452. Sulpho-benzoic acids, 452. Sulpho-urea, 296. Sulphobenzylethylpropylsilicyl oxide, 630. Sulphonal, 136. Sulphones, 89, 90. Sulphonic acids, aliphatic, 99. Sulphonic acids, aromatic, 403. Sulphonium salts, 90. Sulphoxides, 89, 90. Sulphur, detection of, 3. Sulphur, estimation of7 6. Sulphur, valency of, 90. Sulphuric acid as an oxidizing- agent, 622. " Sulphuric ether", 85. Sylvane, 517. Sylvestrene, 576. Sylvestrene derivatives, 578. 5y?i-aldoximes, 139. Syn-d'iazo compounds, 391. Synthetic enzymes, 673. Synthetical terpenes, 576, 578, 580. Syringin, 593. Tagatose, 312. Talitols, 307. Talo-mucic acid, 260, 307. Talonic acid, 307. Taloses, 307, 311. Tannic acids, 460. Tannin, 460. Tar, coal, 340. Tartar emetic, 253. Tartaric acid, 249 et seq. Tartaric acid, esters of, 253. Tartaric acids, inactive, 246, 249, 343. See also Dextro-, Lcevo-, and Parct- tartaric acids. Tartaric acids, stereoisomerism of the, Tartrates, 233. [250. Tartronic acid, 199, 247. Tartronyl urea, 288. Taurine, 196. Taurochohc acid, 196, 668. Tautomerism, 184, 227, 278, 420, 643, 649, Tellurium compounds, 91. [650. Terebenthene, 582. Terephthalic acid, 466. Terpadieneone, 579. Terpadienes, 574. Terpadiol, 580. Terpane, 574. Terpanol, 578, 579. lerpanone, 578. Terpeneone, 579. Terpenes, 567 et seq. Terpenylic acid, 579. Terpin, 580. Terpin hydrate, 581. Terpinene, 572. Terpinene derivatives, 578. Terpineol, 576, 579, 583. Terpmolene, 576. Terpinolene tetrabromide, 578. Tertiary alcohols, 70 et seq. Tertiary-butyl iodide, 60. Tertiary nitro-compounds, 96. Tervalent carbon, 690. Tetra-acet-hydrazide, 185. Tetra-bromo-fluorescei'n, 493. Tetra-bromo-methane, 56. Tetra-chloro-aniline, 374. Tetra-chloro-methane, 56, 64. Tetra-chloro-quinone, 432. Tetra-decane, 30. Tetra-decylcne, 43. Tetra-ethyl-rhpdamine, 493. Tetra-ethyl-silicane, 118. Tetra-ethyl-tetrazone, 112. Tetra-hydro-benzene, 349. Tetra-hydro-benzoic acids, 445. Tetra-hydro-naphthalene, 497. Tetra-hydro-naphthols, 502, 607. Tetra-hydro-naphthylamines, 500, 607. Tetra-hydro-phthalic acids, 466. Tetra-hydro-pyridine, 540. Tetra-hydro-quinoline, 534, 546. Tetra-hydro-quinone, 432. Tetra-hydro-terephthahc acids, 466, 468. Tetra-hydro-xylenes, 351. Tetra-hydroxy-anthra-quinone, 510. Tetra-iodo-pyrrole, 518. Tetra-methyl-ammonium compounds, 1 1 Tetra-methyl-benzenes, 345, 352. Tetra-methyl-diamino-tnphenyl-c,arbino 483- [48; Tetra-methyl-diammo-triphenyl-methani Tetra-methyl-ethylene glycol, 193. Tetra - methyl - phosphomum hydroxidi Tetra-methyl-silicane, 118. [n, Tctra-methyl-stibonium hydroxide, 118. Tetra-methylene, 322. Tetra-methylene-diamine, 195, 598. Tetra-methylene-dicarboxylic acids, 325 Tetra-methylene-imine, 519. Tetra-nitro-methane, 97. Tetra-phenyl-methane, 493. Tetra-phenyl-pyrazine, 551. Tetra-phenyl thiopene, 519. Tetracetylene-dicarboxylic acid, 247. Tetraethyl-phosphonium hydroxide, 114 Tetrahydric alcohols, 201, 202. Tetrazole, 530. Tetrolic acid, 166. Tetroses, 300. Thebaine, 564. Theine, 293. Theobromme, 293. Theophylline, .293. Theory of valency, 13. Thiacetamide, 186. Thiacetic acid, 181. Thiamides, 186. Thiazines, 549. Thiazole, 529. Thio-acetamlide, 382. Thio-acids, 181. Thio-alcohols, 87. INDEX 719 Thio-benzamide, 447. Thio-carbamic compounds, 296. Thio-carbamide, 296. Thio-carbanilide, 524. Thio-carbonic acids, 295. Thio-carbonic compounds, 295. Thio-carbonyl chloride, 295. Thio-cyanates, 275 et seq. Thio-cyanic acid, 275. Thio-cyanic ester, 275. Thio-ethers, 87. Thio-glycols, 191. Thio-phenol, 413. Thio-phosgene, 295. Thio-urea, 278, 296. Thiols, 88, 677. Thionessal, 519. Thiophene, 322, 350, 515, 519. Thiophene-carboxylic acid, 520. Thiophene-sulphonic acid, 520. Thiotolene, 520. Thujenes, 585. Thyme, oil of, 568. Thymo-quinone, 433. Thymol, 408, 417, 579. Tiemann-Reimer reaction, 409, 430, 440. Tiglic acid, 161, 165. Tin, alkyl compounds of, 120. Tin and hydrochloric acid as reducing agents, 602. Tolane, 478. Tolidine, 474. Tolu-quinone, 433. Toluene, 340, 345, 350. Toluene-sulphonic acids, 406. Toluic acids, 443, 452. Toluidides, 382. Toluidines, 367, 375. Toluylene blue, 552. Toluylene red, 552. Tolyl alcohols, 422. Tolyl-acetic acids, 443. Tolyl-diphenyl-methanes, 482. Tolyl-phenyl-methanes, 476. Toxines, icJ6, 598. "Trans" form, 246, 326. Transition temperatures, 255. Tri-acetone peroxide, 181. Tri-amines, aromatic, 381. Tri-amino-azobenzene nydrochloride, 401. Tri-amino-diphenyl-tolyl-methane, 484. Tri-amino-triphenyl-carbinol, 485. Tri-amino-triphenyl-methane, 484. Tri-azo compounds, 695. Tri-azole, 530. Tri-bromacetic acid, 167. Tri-bromaniline, 374. Tri-bromo-phenol, 414. Tri-carballylic acid, 261. Tri-chloraniline, 373. Tri-chlorhydrin, 200. Tri-chloro-acetal, 130. Tri-chloro-acetic acid, 167, 170. Tri-chloro-aldehyde = Chloral, 129. Tri-chloro-benzenes, 357. Tri-chloro-cyanogen, 272. Tri chloro-ethanal, 129. Tri-chloro-methane, 63. Trj-chloro-phenomalic acid, 343. Tri-chloro-propane, 200. Tri-chloro-purine, 290. Tri-cosane, 30. Tri-decylene, 43. Tri-decylic acid, 140. Tri-diphenyl-methyl, 691. Tri-ethylamine, in. Tri-ethyl-arsine, 116. Tri-ethyl-benzene, 342. Tri-ethyl-phosphine, 114. Tri-hydric alcohols, 197. Tri-hydric phenols, 419. Tri-hydrocyanic acid, 269. Tri-hydroxy-anthraquinones, 510, Tri-hydroxy-benzenes, 419. Tri-hydroxy-benzoic acids, 460. Tri-hydroxy-glutaric acids, 259. Tri-hydroxy-purine, 290, 291. Tri-hydroxy-terpane, 579. Tri-keto-hexamethylene, 420. Tri-mellitic acid, 470. Tri-methyl-acetic acid, 157. Tri-methyl-arsine, 116, 117. Tri-methyl-arsine dichloride, 117. Tri-methyl-arsine oxide, 117. Tri-methyl-benzenes, 345, 351. Tri - methyl - carballylic acid = Campho- ronic acid, 586. Tri-methyl-carbinol, 73. Tri-methyl-glycocoll = Beta'ine, 212. Tri-methyl-hydroxyethyl-ammonium hy- droxide Choline, 196. [379. Tri-methyl-phenyl-ammonium hydroxide, Tri-methyl-phosphine oxide, 1 14. Tri-methyl - pyndine - dicarboxylic ester, Tri-methyl-pyridines= Collidines, 539. Tri-methyl-stibine, 117. Tri-methyl-succinic acid, 586. Tri-m ethyl- sulphine hydroxide, 90. Tri-methyl-sulphine iodide, 90. Tri-methyl-sulphonium hydroxide, 90. Tri-methyl-sulphonium iodide, 90. Tri-methyl - vinyl - ammonium hydroxide, Tri-methyl-xanthine, 293. [196. Tri-methylamine, no. Tri-methylamine oxide, in. Tri-methylene, 322. Tri-methylene bromide, 192. Tri-methylene glycol, 192. Tri*nitrin, 201. Tri-nitro-benzene, 362. [ride, 362. Tri-nitro-chloro-benzene = Picryl chlo- Tri-nitro-naphthalene, 499. Tri-nitro-phenol ; see Picric acid, 414. Tri-nitro-tertiary-butyl-toluene, 362. Tri-nitro-triphenyl-carbinol, 481. Tri-nitro-triphenyl-methane, 481. Tri-olei'n ; see Olein, 165. Tri-oxy-methylene, 128. Tri-palmitin, 201. Tri-phenylamine, 379. Tri-phenyl-benzene, 474. Tri-phenyl-carbinol, 422, 481. Tri-phenyl-carbinol-o-carboxylic acid, 491 Tri-phenyl-fuchsine, 489. Tri-phenyl-methane, 471, 481. 720 INDEX Tri-phenyl-methanc-carboxylic acid, 491. Tri-phenyl-methane dyes, 482. Tri-phenyl-methyl, 690. Tri-phenyl-methyl bromide, 481. Tri-phenyl-methyl peroxide, 690. Tri-saccharoses, 299. Tri-stearin, 201. Tri-thio-carbonic acid, 295. Trimesic acid, 470. Trimesic ester, 342. Triple bond, 49. Trisaccharoses, 299, 300, 305, 312. Tropaeoline O, 402. Tropaeolines, 401. Tropei'nes, 565. Tropic acid, 443, 462, 565. Tropidine, 566. Tropine, 565. Tropine-carboxylic acid, 566. Tropinic acid, 566. Trypsin, 598. Tryptophan, 596. Turnbull's blue, 271. Turpentine, oil of, 581. Types, theory of, 13-15. Tyrosine, 459, 596, 670. Tyrosol, 670. Umbellic acid, 464. Umbelliferone, 464. Undecane, 30. Undecylene, 43. Undecyljc acid, 140. Unorganized ferments ; see Enzymes. Unsaturated acids, 161, 434, 679. Unsaturated alcohols, 81, 422. Unsaturated dibasic acids, 241. Unsaturated hydrocarbons, 42, 353. Unsaturated monobasic acids, 161. Unsaturation, types of, 678. Unsaturation and physical properties, Urea, acyl derivatives of, 285. Urea, alkyl derivatives of, 284. Urea, determination of, 283. Urea, salts, &c., of, 283. Urea = Carbamide, i, 281, 282. Ureides, 285, 286 et seq. Ureido-acids, 286 et seq. Urethanes, 282. Uric acid, 290, 291. Uric acid, derivatives of, 294. Uvitic acid, 466. Valency, theory of, 13, 683. Valency of sulphur, 90. Valeric acids, 140, 153. Valero-lactpne, 530. Valero-nitrile, 102. Valerone, i-i-j. Valine, 596. Vanillic acid, 459. Vanillic alcohol, 429 Vanillin, 430, 593. [693- Vapour density, determination of, 9 Vapour pressure, lowering' of, 12. Vaseline, 42. Veratric acid, 460, Victoria green, 484. Victoria orange, 417. Vinegar, 150. Vinyl acetic acid, 165. Vinyl alcohol, 81. Vinyl bromide, 56, 65. Vinyl chloride, 56. Vinyl iodide, 56. Vinyl-ethyl ether, 87. Violuric acid, 288. Viscoid, 318. Viscose, 318. Viscosity, 665. Walden inversion, 661. Wandering of groups, 395. Water blue, 489. Wax varieties, 158. Williamson s blue, 271. Wine, 78. Wine, spirits of, 75. Wintergreen, oil of, 74, 457. Wood gum, 306. Wood spirit, 74. Wood sugar, 306. Wood tar, 74. Xanthjc acid, 296. Xanthine, 292, 599. Xantho-cheudonic acid, 533. Xantho-protei'n reaction, the, 594. . Xanthone, 549. Xylene-carboxylic acids, 453. Xylene-sulphonic acids, 406. Xylenes, 345, 351. Xylenols, 408. Xylidides, 382. Xylidines, 367. Xylitol, 203. Xylo-quinone, 342, Xylose, 306. Yeast, 76, 666. Yeast juice, 667. Yellow prussiate ot potash, 270. Zinc and acid as reducing agents, 60^ et seq. Zinc and alcohol as reducing agents, 608. Zinc and alkali as reducing agents, 608. Zinc dust and acetic acid as reducing Zinc dust and saline solutions as reducing Zinc ethyl, 120. [agents, 609. Zinc methide, 119. Zinc methoxide, 120. Zinc-methyl iodide, 120. Zymase, 77, 304, 667, Zymin, 667. " rB 16754 !4 ( *f / ^*~* UNIVERSITY OF CALIFORNIA LIBRARY