GENERAL PRINCIPLES OF OKGANIC SYNTHESES BY ,; ; : ; , P. ALEXEYEFF/ ',., r' ; J Lot* Professor of Chemistry, University of Kiefi, Ruit\a AUTHORIZED TRANSLATION WITH REVISION AND ADDITIONS BY J. MEKKITT MATTHEWS, PH.D. Head of Chemical Department, School of Industrial Art, Philadelphia. FIRST EDITION FIRST THOUSAND NEW YORK JOHN WILEY & SONS LONDON: CHAPMAN & HALL, LIMITED* 1906 GENERAL Copyright, 1906 BT J. MEREITT MATTHEWS ROBERT DRUMMOND, PRINTER, NEW TOJUt PREFACE. THE present volume has been based on a monograph by Professor P. Alexeyeff (of the University of Kieff), entitled Methods for the Transformation of Organic Compounds (MCTO^H IIpeBpameHiH OprammecKHX'b CoefliraeHift), which originally appeared in 1889 in Russian. In the presentation of the subject in this volume, I have made rather extensive addi- tions of new material, together with a general rearrangement of the entire subject-matter. Professor Alexeyeff, himself, has been deceased these several years, but his widow, Madame Alexeyeff, has very kindly given me authority to employ her husband's book in the preparation of the present volume. I have also to thank Madame Alexeyeff for her kindness in placing at my disposal the originals of her husband's book in Russian, which have been of very material assistance to me in the translation. For the latter purpose I have also made good use of Darzen's and Lefevre's French translation of the original Russian. This book is intended for the general student of advanced organic chemistry, and deals only with the theory of the sub- ject. It is not intended in any way as a laboratory manual for the preparation of organic compounds. Although there are a number of good books of the latter class available for the American or English student, yet I do not believe there is any book in English which covers quite the same ground as the present volume. iii IV PREFACE. The attempt of the author has been to present the theory of organic radicals in a systematic form and in as logical a method of development as possible, so that the student may acquire a comprehensive grasp of the general principles under- lying synthetic organic chemistry. General organic chemistry lias grown so greatly in its mass of detail and in the number of its isolated reactions and separate compounds that the ma- jority of advanced text-books on the subject are now more like complex reference encyclopedias than actual books of in- struction. The student becomes bewildered in an attempt to pick his way through the thousands and thousands of com- pounds dealt with, and loses sight of the underlying path which represents the general principles of the subject. In the present iDook the author has endeavored to discuss general reactions in as broad a manner as possible, though making use of specific reactions for purposes of illustration. In such a treatment it is possible, of course, to become too purely theoretical and to make a few facts the basis of too generalized a reaction, and I fear that in many cases I have erred in this direction. This book, however, is intended to serve merely as a companion volume and to be used in connection with a general organic chemistry, and the latter will prevent the student from carrying too far the generalizations given in this volume. J. MERRITT MATTHEWS. PENNSYLVANIA MUSEUM AND SCHOOL OF INDUSTRIAL ART, PHILADELPHIA, March, 1906. CONTENTS. CHAPTER I. OXIDATION. PAGE 1. GENERAL CONSIDERATIONS i 2. ACTION OF OXIDIZING AGENTS 2 3. DIRECT OXIDATION 15 A. Oxidations which Preserve the same Number of Carbon Atoms in the Molecule 15 B. Direct Oxidation Accompanied by Decomposition of the Mole- cule 29 4. INDIRECT OXIDATION 35 A. Substitution of a Halogen by the Hydroxyl Group 35 B. Oxidation by the Use of Ammonia Compounds 41 C. Conversion of the Sulphonic Acid Group into the Hydroxyl Group 45 D. Substitution of Sulphur by, Oxygen 46 CHAPTER II. REDUCTION. 1. GENERAL CONSIDERATIONS 48 2. ACTION OF REDUCING AGENTS 49 3. SUBSTITUTION OF HYDROGEN FOR HYDROXYL OR OTHER ELEMENT, GROUP, OR RADICAL 51 A. Reduction of Hydroxyl and Ketonic Compounds 51 (1) Reduction of Acids 51 (2) ' ' Aldehydes 53 (3) ' ' Ketones and Quinones 53 (4) " "Alcohols 55 v vi CONTENTS. B. Substitution of Other Groups by Hydrogen 56 (i) Substitution of the Halogens 56 (a) " " " Nitrile Radical 58 (3) " " " Nitro Group 58 (4) " " " Nitroso Group 58 (5) " " " Amido Group 58- (6) " " " Diazo Group 58 (7) " " " Sulphonic Acid Group 60 (8) " "Oxygen 60 (9) " " Sulphur 60 (10) The Removal of Oxygen 60 4. THE FIXATION OP HYDROGEN 60 5. REDUCTION OF NITROSO AND NITRO COMPOUNDS 63 6. ' ' WITH DESTRUCTION OF THE MOLECULE. . 66 CHAPTER III. SUBSTITUTIONS. 1. LAWS OF SUBSTITUTIONS 67 2. SUBSTITUTION OF CERTAIN ELEMENTS OR GROUPS BY OTHERS. ...... 70 A. Preparation of Halogen Compounds 70 B. Exchange of Halogens for One Another 74 C. Substitution of Other Groups by Halogens 77 D. Preparation of the Derivatives of Nitrous and Nitric Acids and of Hydroxylamine 82 E. Preparation of Ammonia Derivatives 93 F. Methods for Obtaining Thio and Sulphur Compounds, and the Acid Esters of Sulphuric Acid 99 G. Methods for the Preparation of Metallo-organic Derivatives. . 106 CHAPTER IV. REMOVAL OF RADICALS. 1. GENERAL CONSIDERATIONS 108 2. REMOVAL OF THE HALOGENS 109 3. MII HALOGEN ACIDS 1 10 4. ' ' WATER 112 5. ' ' AMMONIA 120 6. ' ' HYDROGEN SULPHIDE 120 7. V SULPHURIC ANHYDRIDE 121 8. ' ' CARBON 122 9. MONOXIDE 122 10. " CARBONIC ACID 123 11. " " FORMIC ACID 126 CONTENTS. vu PAGE: 12. REMOVAL OP ACETIC ACID 126 13. " "A HYDROCARBON 126 14. ' ' " ALCOHOL '127 15. " " SIMPLE ETHERS 127 16. " "AMINES 127 CHAPTER V. DIRECT FIXATION OF GROUPS. 1. GENERAL CONSIDERATIONS 129 2. FIXATION OF HYDROGEN. .^ 131 3. " "OXYGEN 131 4. " " HALOGENS 132 A. Fixation of Chlorine 132 B. " " Bromine 133 C. " " Iodine 134 5. FIXATION OF HALOGEN ACIDS 134 6. " "WATER 135 Fixation of Hydrogen Peroxide 139 Sulphide 139 " " Sulphurous Anhydride 1 39 " " Bisulphites 139 7. FIXATION OF AMMONIA 139 8. " " OXIDES OF NITROGEN AND NITROSYL CHLORIDE 140 9. " " HYPOCHLOROUS ACID 141 CHAPTER VI. FIXATIONS ACCOMPANIED BY A DECOMPOSITION OF THE MOLECULE. 1. FIXATION OF WATER 143 A. Hydration Followed by a Rupture of Carbon Bonds 143 B. " " " " " "a Bond between Carbon and Oxygen 145 C. Hydration Followed by a Rupture of a Bond between Carbon and Nitrogen 147 2. FIXATION OF AMMONIA 148 CHAPTER VII. CONDENSATIONS. 1. CONDENSATION BY DIRECT ADDITION 150 2. " " DOUBLE DECOMPOSITION, OR BY REMOVAL OF GROUPS 158 A. Formation of Ethers and Analogous Bodies 158 vrn CONTENTS. PAGB .1) With the Liberation of a Mineral Acid or of a Salt 158 (2) Formation of Ethers, etc., with Liberation of Water 162 (3) ' ' Esters, " " of Ammonia . or Nitrogen 164 B. Preparation of Compounds containing Sulphur 165 C. " " " " Nitrogen 167 (1) Ammonia Derivatives 167 (a) Derivatives Formed with Liberation of Halogen Acids or other Acids or Salts 167 (6) Ammonia Derivatives Formed with Liberation of Water 169 (c) Ammonia Derivatives Formed with Liberation of HaS i74 (d) Ammonia Derivatives Formed with Liberation of NH S 175 (2) Derivatives of the Diamines and the Diimides 176 (a) Substituted Hydrazines 176 (6) Diazo-amido Compounds 177 (c) Azo Derivatives 178 (d) Azoxy Compounds 180 CHAPTER VIII. TYPES OF SYNTHESES. 1. FIXATION OF CARBON MONOXIDE 182 2. " " " DIOXIDE 183 3. CONDENSATION BY THE TRANSFORMATION OF THE CO GROUP INTO C.OH AND C.OX 185 4. CONDENSATION WITH Loss OF WATER 191 5. " " " OF A HALOGEN ACID, OF A METALLOID, OR OF A SALT 200 6. CONDENSATION WITH LIBERATION OF HYDROGEN 212 7. " " " " WATER AND HYDROGEN 214 8. " " " " CO 2 214 9. POLYMERIZATION 215 CHAPTER IX. ISOMERIZATION 217 UNIVERSITY GENERAL PRINCIPLES OF ORGANIC SYNTHESES- CHAPTER I. OXIDATION. I. GENERAL CONSIDERATIONS. OXIDATION is one of the most important reactions in the synthesis of organic compounds. The element carbon has an especially strong attraction for oxygen, and nearly all organic compounds are more or less amenable to its action, either in a direct or an indirect manner. The compounds of the paraffin series, or, more properly, the open-chain series, are more susceptible to oxidation than those of the benzene or closed-ring series; and the extent to which the oxidation may be carried may vary within considerable limits, the final limit in all cases being the decomposition of the molecule into carbon dioxide and water. Oxidation may operate in a large number of different direc- tions, and by the use of an extensive series of reagents. In a number of instances the exact phase which the oxidation assumes will be dependent upon the nature of the reagent employed, 1 and many other conditions of the reaction; in some 1 When choline is treated with concentrated nitric acid, it is oxidized to muscarine: CH.O OH CH 2 .N(CH 3 ) 3 .OH Choline. Muscarine. But when treated with either potassium permanganate or chromic acid mix- ture, negative results are obtained. CH, 2 ORGANIC SYNTHESES. cases, it is possible to direct the mode and extent of the oxida- tion by a careful selection and proper regulation of the various conditions, and in this manner arrive at will at different results from the same starting-point. In other cases, the reaction is- not so readily subject to control, and its variations may be very limited. The elements and radicals occurring in organic compounds which are capable of oxidation, in one manner or another, are quite numerous. Carbon, as already mentioned, is especially susceptible to the action of oxygen; so also is hydrogen, and to a less degree sulphur and nitrogen, together with phosphorus and the allied elements which occur in a few of the carbon com- pounds. The halogens cannot be considered as oxidizable in the proper sense of the word. The various metals which may occur in organic combinations, in most instances, may be con- sidered as subject to oxidation. But the majority of the re- actions which have been carefully studied are limited to com- pounds including carbon, hydrogen, nitrogen, and sulphur as- the elements subject to oxidation. In the oxidation of the hydrocarbon nucleus (which in. reality comes down to the methyl radical, CHa, as the unit), both the hydrogen and the carbon may take part in the reaction.. Starting with methane, CH 4 , as the most highly-reduced com- pound of carbon, the following successive stages of oxidation may be indicated : (1) The oxidation of a single hydrogen atom to an hydroxyl group: CH4 + 0=CH 3 .O.H; in this case but a single valence of the carbon atom is oxidized,, and there is no removal of hydrogen. (2) The removal of a single hydrogen atom by oxidation to> water, and the formation of the oxide of the radical : OXIDATION 3 this reaction may be considered as the amplification of the foregoing : 2CH 3 .OH - H 2 = (3) The removal of two hydrogen atoms in the form of water, and the formation of an unsaturated compound : CH 2 2 CH4+2CHI +2H 2 0; CH 2 this reaction may also be considered as an amplification of the first: CH 3 OH CH 2 -2H 2 0= || CH 3 OH CH 2 (4) The removal of two hydrogen atoms in the form of water and the simultaneous introduction of an oxygen atom in their place : in this case, both the hydrogen and carbon are oxidized; the former to water and the latter to the carbonyl group, C : 0, for the above compound is the aldehyde, 1 H.C /a \o- (5) The oxidation and removal of two hydrogen atoms as water, and the simultaneous oxidation of another hydrogen atom to the hydroxyl group and of the carbon to the carbonyl group: CH4+30 =H 1 The intermediate reaction, that of the oxidation of two hydrogen atoms to hydroxyl groups without the elimination of water, does not appear to take place, as two hydroxyl groups cannot be attached to the same carbon atom, a mole- cule of water splitting off with the consequent formation of a carbonyl group: CH 4 + 20= CH 2 /OH H 2 C : O+ H 2 O. 4 ORGANIC SYNTHESES. (6) The oxidation and removal of all the hydrogen as water r and the simultaneous oxidation of the carbon to carbon di- oxide: CH 4 +40 = 2H 2 0+C0 2 . From the above considerations it may be seen that the oxidation of hydrocarbons may occur along the following general lines: (1) Oxidation by removal of hydrogen in the form of water. (2) Oxidation of hydrogen to hydroxyl. (3) Oxidation of carbon to carbonyl. 1 In the first case, oxygen itself does not enter the molecule. This character of reaction is not a very general one, and when it does occur is usually brought about in an indirect manner. It leads to the formation of unsaturated compounds or con- densation products. In the last two cases, oxygen enters the molecule, but there is a difference in its mode of combination; in the second re- action only one valence of the carbon atom is held by oxygen, the second valence of the latter atom being attached to hydro- gen (the hydroxyl group, alcohols) or to another similar ele- ment or group (the alcoholates, ONa, the ethers, O.CH 3r etc.). In the third reaction, both the valences of the oxygen atom are directly attached to the carbon to form the carbonyl group, =C:0 (the aldehydes, -HC:0, the ketones, =C:0, and the acids, -C:O.OH). Some processes of oxidation occur with much more readiness than others; for instance, the direct oxidation of a hydrogen atom in a hydrocarbon nucleus to the hydroxyl group is rather rare, and will only take place under certain conditions : CH 4 + 0->CH 3 .OH. A group, however, already containing oxygen is more susceptible of oxidation as a rule. For instance, the alcohol, CH 3 OH, is 'See also A. Wagner, Action of Oxidants, Warsaw, 1888 (Russian). OXIDATION. 5 rather easily oxidized to the aldehyde : CH 3 .OH + 0-H.CH:0. S In the case of compounds containing several hydrocarbon residues, it is recognized as a general law that when an alcohol is further oxidized the second oxygen atom becomes attached to the carbon atom already joined to the hydroxyl group., This causes the attachment of two hydroxyl groups to a single carbon atom, which is a very unstable grouping and immediately breaks down with the elimination of water and the formatioa of the carbonyl group: CH 3 CH 3 I +o - | / CH 2 .OH CH< \ CH 3 CH 3 /QH -> | +H 2 CH \OH CH:0 In the case of primary alcohols containing the group CH 2 .OH, further oxidation causes the formation of alde- hydes, having the group CH:0; with secondary alcohols, or those containing the group >CH.OH, ketones are formed with the group >C:O. InAhe case of tertiary alcohols, or those containing the group -^C.OH, as there are no more hydrogen atoms capable of oxidation to hydroxyl, the molecule is broken down with the formation of acids having a less number of carbon atoms. As the aldehyde group still contains a hydrogen atom,, it may be further oxidized with the formation of acids: -CH:0 + -> -CO.OH. Ketones, on the other hand, cannot be further oxidized; if the oxidant employed is sufficiently powerful, the ketone is broken up into compounds having a less number of carbon atoms. In order to show the various possibilities in the oxidation ORGANIC SYNTHESES of the methyl group, or its derivatives, the following list of the theoretical product of propane is given : 1 . CH 3 CH 2 .OH (2) CH 3 . (3) CH 2 .OH CH 2 CH 2 CH.OH CH.OH 1 1 1 1 CH 3 . CH 3 . CH 3 CH 3 Propane. Primary propyl alcohol. Secondary propyl alcohol. Propylidene glycol. (4) " (5) (6) (7) CH 2 .OH i CH:0 i CH 3 i CH 2 .OH i CH 2 CH 2 io CH.OH I 1 1 I CH 2 .OH CH 3 CH 3 CH 2 .OH Propylene Propyl-aldehyde Acetone. Glycerol. glycol. (8)* (9)* (10) (11) CH:0 i CH:0 i CH 2 .OH i COOH. i CH 2 CH.OH CO CH 2 1 1 1 1 CH 2 .OH CH 3 CH 3 CH 3 Acetol. Propionic acid. (12) CH 2 .OH (13)* CH 2 .OH (14)* CH:0 (15)* CH 3 CH.OH io CH 2 CO 1 1 1 1 CH.-O CH 2 .OH CH:0 CH:0 Glyceric aldehyde. (16) CH 2 .OH (17) CH 3 (18)* CH:0 (19)* CH:O CH 2 CH.OH CH.OH CO CO.OH CO.OH CH:0 CH 2 .OH Ethylene Ethylidene lactic acid. lactic acid. 1 Hjelt (trans. Tingle), Principles of General Organic Chemistry, p. 105. OXIDATION. (20) (21) (22) (23)* CH:0 CH 3 CH 2 .OH CH:0 I I I I CH 2 CO CH.OH CH.OH CO.OH CO.OH CO.OH CO.OH Fonnyl acetic Pyroracemic Glyceric acid. acid. acid. (24)* CH 2 .OH (25) CO.OH (26)* CH:0 |o CH 2 i CO.OH CO.OH CO.OH (27) CO.OH H.OH A i, OH Malonic Oxymalonic acid. acid. (28) CO.OH I co.< .OH Mesoxalic acid. The compounds whose formulas are unnamed and marked Tvith an asterisk have not yet been prepared. Aromatic compounds, or those containing closed rings of carbon atoms, are not as readily oxidized in general as open- chain compounds. Oxidation of a compound containing a ben- zene ring, together with a side chain, usually results in the con- version of the latter into the carbonyl group; and it makes no difference how extensive or complicated the side-chain may be, 1 1 When several side-chains are present in aromatic compounds, their rela- tive position in the molecule exerts considerable influence on the direction and extent of oxidation For instance, dilute nitric acid does not oxidize metaxylene, C 6 H 4 (CH 3 ) 2 , whereas it oxidizes paraxylene to paratoluic acid, C 6 H 5 .CO.OH. The reaction may sometimes be controlled by the use of mild oxidizing agents, as, for instance, in the oxidation of cymene : CH 3 e prr 3 o.4\ fYrvm L \CH 3 \CH and CeH, and , PTT. , .OH and C 6 H and TT /CO. S \CH 3 II. ACTION OF OXIDIZING AGENTS. Oxidation may be brought about either directly by the action of a suitable oxidizing agent (as in the oxidation of anthracene to anthraquinone by the action of chromic acid) or indirectly through the formation of intermediate compounds (as in the preparation of phenol from benzene by first sulpho- nating the latter by treatment with sulphuric acid, and then fusing the sulphonic acid so obtained with caustic potash) : 1 1 Lassar-Cohn makes the following remarks in regard to the carrying out of oxidations in organic chemistry: (a) When the product of oxidation is readily decomposed by the further action of the oxidant, it is frequently possible to add to the solution a carefully chosen extracting solvent, so that on the addi- tion of the oxidant the whole may be shaken and the product removed from the influence of the latter by the solvent. The use of ice for the purpose of main- taining a low temperature also has a beneficial effect at times, (b) If the product of oxidation is volatile in steam, a current of the latter may be conducted through the solution during the oxidation, (c) In many cases where the preparation of a particular oxidized product is especially difficult, it is frequently possible to judiciously choose some derivative of the substance to be operated on, which by proper treatment will yield the same product. Manual of Organic Chemistry (trans. Smith), p. 244. OXIDATION. OTT PO (a)3C 6 H 4 < / | \CeH4 + 2Cr0 3 = 3C 6 H 4 / X CH/ X CO +3H 2 0+Cr 2 3 . (b) C 6 H 6 -fH 2 S0 4 =C 6 H 5 .S0 2 .OH C 6 H 5 .S0 2 .OH + KOH = C 6 H 5 .OH + KHS0 3 . Oxidation may also occur in two different directions: (ajs The compound may contain the same number of carbon atoms^ after oxidation as before : CH 3 .CH 2 OH + = CH 3 .CH : + H 2 (X Alcohol. Aldehyde. (b) The oxidation may be accompanied by a decomposition of the molecule, with the formation of two or more substances containing fewer carbon atoms than the original compound: CH 3 .CO.CH 3 + 20,. = CH 3 .CO.OH + C0 2 + H 2 0. Acetone. Acetic acid.' Carbon dioxide. This latter form of oxidation is especially liable to occur witla the unsaturated compounds of the aliphatic series, as in the oxidation of crotonic acid to a mixture of acetic and oxalic acids, COOH CH 3 .CH : CH.CO.OH + 20 2 = CH 3 .CO.OH + 1 Crotonic acid. Acetic acid. COOH Oxalic acid.- or of allyl alcohol to formic and oxalic acids : CO.OH CH 2 : CH.CH 2 .OH + 30 2 = H.CO.OH + 1 Allyl alcohol. Formic acid. QQ QJJ Oxalic acid. In such cases the compound, as a rule, breaks down at the position of the double bond. In some reactions, oxidation may result in the condensation! of the compound, either in its own molecule or with other sub- stances, by reason of the elimination of hydrogen by the oxygeiu. 10 ORGANIC SYNTHESES. For instance, the oxidation of dibenzyl leads to the formation of toluylene : C 6 H 5 -CH 2 C 6 H S -CH +0= || Hr< TT rTT 2 L/6A15 L/Jtl Dibenzyl. Toluylene )-"--*-{J VXJ aJ] jii* (J The formation of pararosanihne by the oxidation of a mixture of aniline and paratoluidine is also an illustration of this re- action: ]H"HjC 6 H4.NH 2 ~ : jlT"HiC 6 H4.NHiHl A large number of different bodies may be employed as oxidants, though the action of different oxidants may vary considerably towards the same organic compound. The oxi- dation of aniline by various oxidants may be taken as an illus- tration. When treated with a mixture of manganese dioxide and sulphuric acid, aniline yields ammonia and a small amount of quinone. 1 When oxidized with chromic acid mixture, how- ever, a quantitative yield of quinone is obtained; with an al- kaline solution of potassium permanganate, aniline is con- verted into azo-benzene, ammonia, and oxalic acid; 2 whereas, in an acid solution, the same oxidant gives aniline black, and, in a neutral solution, nitre-benzene and azo-benzene are formed; 3 boiled with a solution of bleaching-powder, 4 aniline gives nitro- benzene; with an acid solution of hydrogen peroxide, ammonia * C 6 H 6 .NH 2 +0 2 =C 6 H 4 0+NH 3 . > 3C 6 H s .NH.+ 50=C 6 H 6 N:N.C 6 H a + NH 3 + (COOH) 2 +H 2 O. 3C 6 H 6 .NH 2 + 30= C 6 H 5 .N : N.C 6 H,+ C 6 H 5 .NO 2 + 3H 2 O. 4 Ortho-nitrobenzal-acetone is converted into ortho-nitro-cinnamic acid by the oxidizing action of sodium hypochlorite (mixture of bleaching-powder and OXIDATION. II and dianilido-benzoquinone-anilide is formed; while, in a strong acid solution, the same oxidant gives an induline derivative. 1 The following summary gives the principal oxidizing agents employed, together with a brief account of their action: 2 Oxygen acts directly only on easily oxidizable substances. Air, when acting in the presence of heated platinum or platinum sponge, will oxidize primary alcohols to aldehydes, and even aldehydes themselves are gradually converted into acids. Formaldehyde, for instance, may be prepared by conducting a mixture of methyl alcohol vapor and air over a heated platinum spiral. The hydrochloride of paraphenylene-diamine is easily oxidized by exposure to the air, giving almost a theoretical yield of tetra-amido-diphenyl-para-azophenylene : N:C 6 H 3 .NH 2 By passing the vapors of many 'substances mixed with air over a heated spiral of copper superficially oxidized, oxida- tion products are obtained, as a rule, more readily than with a platinum spiral. Ethyl ether, for instance, is oxidized to aldehyde, CH3.CH2 \r\ CHg.CHO , TT r\. CH 3 .CH 2 / U * CH 3 .CHO + and toluene gives benzaldehyde : C 6 H 5 .CH 3 -> C 6 H 5 .CHO.+H 2 0. sodium carbonate): 1 Benzylidene-acetone is converted into cinnamic acid by the oxidizing action of bromine in alkaline solution. The oxidizing action of bromine has also been made use of among the carbohydrates; for instance, by heating nsrtk-sugar with bromine an acid is formed; by heating glycerol with bromine and soda-ash, glycerose is formed. 2 For a detailed discussion of the different oxidizing agents employed in organic syntheses, see Lassar-Cohn, Manual of Organic Chemistry, pp. 243-286. 12 ORGANIC SYNTHESES. Silver oxide in alkaline solution readily oxidizes aldehydes to acids, with the precipitation of metallic silver : 2CH 3 .CHO + 3Ag 2 = 2CH 3 .COO.Ag + H 2 -f 2A g2 . Glycerol is converted into gly collie acid. The ammoniacal solution of silver oxide for the testing of aldehydes is best pre- pared by mixing a solution of 10 parts silver nitrate in 100 parts water with one of 10 parts caustic soda in 100 parts water, :and then adding ammonia-water drop by drop until the pre- cipitate of silver oxide has completely dissolved. The solution should be kept in a dark place. Manganese dioxide is used in connection with sulphuric acid 'for oxidation in acid solutions. When the vapor of alcohol is conducted over pyrolusite heated to 150-360 C v it is mostly ^converted into acetone. Potassium permanganate is perhaps more frequently used than any other oxidizing agent. It may be employed in neutral, .acid, or alkaline solution. 1 In neutral solution it acts as follows : 2KMn0 4 +xH 2 0= 2Mn0 2 .xH 2 0+2KOH + 30. In alkaline solution the reaction is the same. In acid solution It is as follows : 2KMn0 4 + 3H 2 S0 4 = 2MnS0 4 + K 2 S0 4 + 3H 2 4- 50. Compounds containing hydrogen, linked to a tertiary carbon atom, have the hydrogen converted into hydroxyl by the action of an alkaline solution of potassium permanganate : T) T? R-^CH - R^C-OH. ^ R/ R/ _ 1 Reichardt, in his investigations on the action of different oxidizing agents on soluble starch, found that potassium permanganate in acid, alkaline, and neutral solutions, and chromic acid, have an energetic action, but all give rise to indefinite, dirty-brown products; chlorine and alkaline copper hydrate solu- tion gave the same result; but by warming the starch solution with bromine and afterwards treating the product with silver oxide, gluconic acid was obtained. Starch heated with nitric acid gave carbon dioxide and oxalic acid, whereas .fuming nitric acid gave a mono-nitro-derivative. OXIDATION. 13 The group =CH 2 is usually converted into CO by the action of potassium permanganate. Chromic acid is extensively used for the preparation of alde- hydes, ke tones, and acids from alcohols; for the oxidation of aromatic hydrocarbons (with the exception of the ortho-com- pounds), and for 'the preparation of quinones. Chromic acid is almost always used in acetic acid solution, as, when dissolved in water, it gives a precipitate of chromic oxide. 1 A mixture of potassium bichromate and sulphuric acid may also be used; this is known as "chromic acid mixture." For the oxidation of the aromatic hydrocarbons, a mixture of 4 parts K 2 Cr 2 7 and 6 parts H 2 S0 4 , diluted with twice its volume of water, is found to be most suitable. In the case of alcohols a more dilute solution is necessary. Many compounds, such as oxy- acids, ketones, etc., may be decomposed by chromic acid mix- ture, with the formation of products containing less carbon atoms. A mixture of potassium bichromate and acetic acid is sometimes used; other acids may also be substituted. The oxidizing power of these mixtures is calculated on the principle that the Cr0 3 is converted into Cr 2 3 : K 2 Cr 2 7 + 4H 2 S0 4 = K 2 S0 4 + Cr 2 (S0 4 ) 3 + 4H 2 + 30. i ; Chromyl chloride is another useful oxidizing' agent, es- pecially for converting the methyl groups in aromatic hydro- carbons into aldehyde groups. Thus, nitro toluene is con- verted into nitrobenz aldehyde. Chromyl chloride is prepared by acting on a mixture of salt and potassium bichromate with fuming sulphuric acid : K 2 Cr 2 7 + 4NaCl + 3H 2 S 2 7 = 2Cf 2 C1 2 + K 2 S0 4 + 2Na 2 S0 4 + 3H 2 S0 4 . * - 1 The formation of the oxide may sometimes interfere with the proper course of the reaction, especially in the case of organic acids, where the latter may com- bine with the oxide. Should the solution of chromic acid in water be used, it is best to acidify it with sulphuric or hydrochloric acid. The use of an acetic acid solution, however, is further favored by the fact that many of the bodies which it is the purpose to oxidize may be dissolved therein, and the speed of oxidation then regulated by gradual addition of chromic acid. 14 ORGANIC SYNTHESES. The action of chromyl chloride is very violent, and it must be used in carbon disulphide solution. It is probable that at first double compounds are formed between the hydrocarbons and the chromyl chloride, which are decomposed by water with the formation of aldehydes : 3C 6 H5.CH 3 (Cr0 2 Cl2)2 = 3C 6 H 5 .CHO +2Cr 2 Cl 6 + 2Cr0 3 +3H 2 0. Nitric acid may be used as an oxidant, though it also has a nitrating action. When employed as an oxidant, nitric acid diluted with two molecules of water is generally used; such an acid acts less energetically than chromic acid mixture. Con- centrated nitric acid usually converts compounds of the methane series into oxalic acid or carbon dioxide. Caustic potash acts as an oxidant when it is fused with the substance. The higher primary alcohols in this manner yield acids. Phenols, when fused at high temperatures with caustic potash, give diphenols. 1 Unsaturated compounds are usually decomposed by fusion with caustic potash, the carbon chain being broken at the position of the double bond, the products being oxidized to acids. Hydrosorbic acid, for instance, gives acetic and butyric acids : CH 3 .CH : CH.CH 2 .CH 2 .CO.OH + 2KOH Hydrosorbic acid. = CH 3 .COOK + C 3 H 7 .COOK + H 2 . 1 Oxidation produced through fusion with caustic potash is a peculiar one. Prima y alcohols are converted directly into acids: C^Hgg. OH+ KOH= C 16 H 33 O.OK+ 2H, Cetyl alcohol. Palmitic acid. Phenols are also oxidized by the same means at high temperatures, the reac- tion varying with the composition of the phenol, hydrogen being evolved in each case. Phenol, for example, gives diphenol: 2C 6 H 5 .OH+ 2KOH= KO.C 6 H 4 .C 6 H 4 .OK+ H 2 + 2H 2 O. Resorcinol gives diresorcinol and some phloroglucinol: C 6 H 4 . (OH) 2 + 3KOH= C 6 H 3 (OK)> 2H 2 O+ H^ With cresol, the side-chain is oxidized: C H \CH 3 +2KOH=C ^\COOK+3H 2 . OXIDATION. 15 III. DIRECT OXIDATION. A. Oxidations which Preserve the Same Number of {Jarbon Atoms in the Molecule. Attention has already been drawn to the fact that oxida- tion may be either direct or indirect, and that the former mode may in turn be subdivided into (1) oxidation which preserves the same number of carbon atoms in the molecule, and (2) oxidation accompanied by a greater or less destruction or breaking-down of the molecule. When the destruction of the body is complete, with the formation of carbonic acid, the oxidation is termed combustion. The various radicals or groups to be met with in organic chemistry will now be examined with reference to their be- havior with oxidants. The -CH 3 group is oxidized almost exclusively only in aromatic compounds. It is then changed into the aldehyde group, -CHO, or the carboxyl or acid group, -CO. OH. It is difficult to cite any examples in the paraffin series of the oxi- dation of the -CH 3 group into -CHO or -CO.OH; about the only cases known are the conversion of butyric acid into suc- cinic acid, and the production of glyoxal by the oxidation of aldehyde : CH 2 .CH 3 ~ CH 2 .CO.OH CH 3 ., CHO CH 2 .CO.OH CHa.CO.OH CHO CHO Butyric acid. Succinic acid. Aldehyde. Glyoxal. The CH 3 group is converted into CHO 1 by decomposing with water the double compounds of the aromatic hydrocarbons with chromyl chloride. The compound with toluene, for example, should apparently be represented by the following formula: 'O.CrCl 2 .OH 1 The oxidation of the CH 3 group into CHO may be effected by employing air in the presence of an oxidized copper spiral (Low, Jour. pr. Chem., vol. 91 p, 323). By this means toluene, C 6 H 6 .CH 3 , is converted into benzaldehyde, C 6 H 6 .CHO. (See above.) 16 ORGANIC SYNTHESES. The decomposition with water evidently proceeds in accordance with the following equation: + 3H 2 = 3C 6 H 5 .CHO + 2Cr 2 Cl 6 + 2Cr0 3 + 6H 2 0. The operation is carried out in the following manner : 1 Dissolve 1 part (1 mol.) of the hydrocarbon in 7 parts of carbon disulphide, and gradually add, with cooling, 10-15 parts of a solution of 1 part (2 mols.) of chromyl chloride in 7 parts of carbon disulphide; after each addition wait until the red coloration has disappeared. The precipitate is collected on some glass wool, washed with carbon disulphide, and dried on a water-bath. It is then decomposed by gradually pouring into cold water, and the aldehyde is removed by means of ether. The aldehyde may also be isolated by treating the solution with a current of sulphur dioxide gas. Chromyl chloride, acting on aromatic hydrocarbons with side-chains, transforms them into aldehydes; with benzene, however, quinone is formed. By the aid of chromyl chloride, not only can the CH 3 group in hydrocarbons be transformed into CHO, but also in their derivatives. For instance, the compound propylphenyl-ketone, C6H 5 .CO.CH 2 .CH 2 .CH 3 , when oxidized, gives benzoyl-propylic aldehyde, C 6 H 5 .CO.CH 2 .CH 2 .CHO. 2 The CH 3 group in aromatic compounds is converted into CO.OH by the action of most oxidants. In this manner the hydrocarbons are transformed into organic acids either by dilute 1 Chromyl chloride is prepared in the following manner: Fuming sulphuric .acid is added to a mixture of common salt and potassium bichromate in the pro- portions indicated by the following equation: K 2 Cr 2 7 + 4NaCl+ SH^O, = 2CrO 2 Cl 2 + ig3O 4 + 2N a2 SO 4 + SH^O,. The mixture is distilled from a large flask until the contents begin to foam. A secondary reaction, resulting in the liberation of chlorine, proceeds according to the following equation: 6CrO,Cl 2 + SHj&Or- 2Cr 2 (SO 4 ) 3 + 2Cr0 3 + 6C1 2 + 3H 2 0. 2 Burcker, Ann. de Chem. et de Phys., vol. 26, p. 470. OXIDATION. 17 nitric acid, chromic acid mixture, 1 potassium permanganate, or even by fusion with caustic potash. The fusion with caustic potash is principally employed for the purpose of oxidizing the CH 3 group in phenols. This fusion should be carried out at a temperature of 200-250 C. for several hours; 4 to 5 parts of caustic potash (KOH), moistened with a little water, are used for 1 part of phenol. The end of the reaction is indicated by the liberation of hydrogen ceasing. In the case of amido derivatives, the NH 2 group should be preserved against the action of oxidants by the introduction of an acid radical; otherwise there would result quinones and azo- compounds. Thus, ^ r R /(I) CH 3 6l4 \(4) NH.CO.CHs Acetyl-paratoluidine. gives, on oxidation, coo* rH /(l)CO.OH UM4 \(4) NH.CO.CHs* Acetyl-paramido-benzoic acid. The presence of the N0 2 group often protects the NH 2 group from oxidation: thus, dinitrotoluidine, on oxidation with chromic acid mixture, gives amido-dinitro-benzoic acid : CH 3 COOH NH 2 NH 2 Frequently different oxidants do not behave in the same //-i \ p~CT manner. Thus orthotoluic acid, C 6 H 4 <^ L) COOH' ^ ves phtha- lic acid when oxidized by potassium permanganate; but when treated with chromic acid mixture it is completely decomposed 1 In place of chromic acid mixture (4 parts potassium bichromate and 5 parts sulphuric acid) there may be employed a solution of chromic acid in glacial acetic acid. 1 8 ORGANIC SYNTHESES. / '/1\ into carbonic acid. In the same way cymene, C 6 H 4 \ ,*( n -r > \W ^3*17 by the oxygen of the ah- (as in the animal organism), is trans- formed into cuminic acid, C 6 H 4 ^ m jj > by the oxidation of the CH 3 group and transformation of the C 3 H 7 group into its isomeric form; but when oxidized with dilute nitric acid, it is the C 3 H 7 group which is attacked, and paratoluic acid is produced, l poOH' w ^ c h on father oxidation yields terephthalic acid, C 6 H4<^ ^J, COOH' ^ ien ^ ne aroma ti c hydrocarbon con- tains groups other than CH 3 and of the formula C n H 2n +i, they are oxidized like CH 3 and are all transformed into COOH. Thus r ethyl-benzene, C 6 H 5 .CH 2 .CH 3 , on oxidation gives benzoic acid, CeHs.COOH. If, besides these groups, the hydrocarbon con- tains another side-chain of CH 3 , the latter is oxidized subse- quently, as in the case of the oxidation of cymene to paratoluic acid, and then to terephthalic acid. The presence of the acid groups, N0 2 , COOH, S0 2 OH, ren- ders the oxidation more difficult. Thus, while toluene, C 6 H 5 CH 3 ,. /Cl and its mono-chlor derivative, CeH 4 <^ ^ -^ , are easily oxidized by the action of dilute nitric acid, nitro-toluene, CeH^ pjr 2 > is only oxidized by chromic acid mixture, or by heating with dilute nitric- acid in a sealed tube; and the corresponding dinitro-derivative,. C 6 H*\ n-cj j is not oxidized by even chromic acid mixture. ^\uti 3 If the CH 3 is in the ortho (1:2) position with an acid group,, it cannot be oxidized by either nitric acid or chromic acid mixture; it is necessary to use potassium permanganate in al- kaline solution, or fusion with potash. Furthermore, it should be noted that in the oxidation of unsymmetrical pseudocumene, C 6 H 3 (CH 3 ) 3 (l-2:4), by dilute nitric acid, there are formed two isomeric acids, C 6 H 3 ^ /nTJ N r Xw-ti 3 j 2 OXIDATION. 19 xylilic and paraxylilic acids, according to which CH 3 is oxidized; but in the oxidation of the symmetrical hydrocarbon, mesity- lene, C 6 H3(CH 3 )3 (1:3:5), there is only one acid obtained, R" and || >R", as anthracene, CH/ x CH CG^ ;>CeH4 and phenanthrene 1 1 can be explained / CH C 6 H4 by admitting the formation of 2(C.OH), which fixes + H 2 O r and then splits off water, 2H 2 0. Thus, with anthracene there OlHl /\ iOH!\ is first formed, C 6 H 4 OCH.CHOH.CHOH.COOH. The CH 2 OH group on oxidation is changed into CO. OH or CHO. 1 It is converted into CO.OH by the action of numerous oxidants, and, in certain cases, by the action of atmospheric oxygen in the presence of platinum .black. 2 It was in this manner that Grimaux 3 prepared the first synthetic sugar by oxidizing glycerol. Primary alcohols by this means can be converted into acids. The action of the platinum black is at times too energetic, and the reaction must be moderated by diluting the alcohol with water. If the alcohol is very volatile, 1 The mechanism of these reactions is as follows: -CH|H|0|H|+ |O|= -CHO+H 2 O the alcohol group may also be considered in some cases as being directly oxidized to the acid, as follows: - C|HH|.OH+|0|b= - This is a very probable assumption, because the H in the hydroxyl group of the alcohol is already oxidized, and when the acid is formed directly it is more likely that the two H's of the nucleus are oxidized and removed, rather than one H from the nucleus and one from the hydroxyl group. In fact, the first oxida- tion of the alcohol group to the aldehyde may be more logically considered as: -CH.HOH+ 0= -CH - H 2 O= -CHO. 2 The CH 2 OH group may be oxidized to the CHO group by means of air in the presence of platinum. (Hofmann, Ann., vol., 145, p. 358; Tollens, Ber., vol. 19, p. 2133.) This was the first method employed for the preparation of formaldehyde, H.CHO, from methyl alcohol, CH 3 .OH. Superficially oxidized copper has been found to be even more effective than platinum. (Low, Jour. pr. Chem., vol. 141, p. 323.) 3 Bull. Soc. Chim., vol. 45, p. 481. OXIDATION. 23 place it in a beaker beside another one containing the platinum black, and cover the whole with a watch-glass. The CH 2 OH group is converted into CHO usually by means of chromic acid mixture, this being the customary method of preparing aldehydes. It is necessary to take a slightly less quantity of alcohol than the theoretical amount. 1 As secondary products, there are obtained acetals and ethers by reason of a more advanced oxidation giving rise to some acid which reacts on the alcohol. The aromatic aldehydes are often obtained in a different manner. The chloride corresponding to the alcohol does not yield the latter very readily, but it may be directly transformed into the aldehyde by heating with a nitrate, and lead nitrate in particular. It may be that the nitric ether, which is at first formed, is saponified by the water, and the nitric acid thus liberated oxidizes the alcohol into the aldehyde. In order to obtain aldehydes by the decomposition of ordinary ethers, see p. 55; and for the action of quinone on alcohol, see p. 54. The CHO group of aldehydes is oxidized to CO. OH by the action of chromic acid mixture, alkaline solution of potassium permanganate, etc., or by gradually adding to the solution of the aldehyde in glacial acetic acid the theoretical amount of chromic acid dissolved in the same solvent. The unsaturated aldehydes are easily oxidized by the action of silver oxide. Aldehydes are also oxidized directly by atmospheric oxygen : 1 The CH 2 OH group in choline, CH 2 .OH, however, gives negative re- CH 2 .N(CH 3 ) 3 .OH suits when efforts are made to oxidize it with potassium permanganate or with chromic acid. With concentrated nitric acid, however, muscarine, CH XOH \OH , was easily obtained. Like other similar bodies, this formula CH 2 .N(CH 3 ) 3 .OH for muscarine is open to doubt: it probably has the form of the customary alde- hyde: CH:0 I +H 2 0. CH 2 .N(CH 3 ) 3 .OH 24 ORGANIC SYNTHESES. thus vanillin, on exposure to the air, is gradually converted into vanillic acid; benzoic aldehyde, into benzoic acid; a-naphthoic aldehyde, very easily into a-naphthoic acid, etc. The aromatic aldehydes are oxidized in the air by fusion with caustic potash, and often even by the action of an alcoholic solution of potash. In the latter reaction there is formed at the same time the reduction product of the aldehyde: C 6 H 5 .C!HJO KO C 6 H 5 .CO.OK T + C 6 H 5 .CHO H C 6 H 5 .CH 2 .OH This reaction is peculiarly interesting in that it presents an oxidation and a reduction proceeding simultaneously on the same substance. It seems rather difficult to understand just how a hydrogen atom migrates so illogically from one mole- cule to another. It may be that the reaction takes place after this fashion: C 6 H 5 .CH04- +C 6 H 5 CHO _C 6 H 5 CH 2 .0!K _C 6 H 5 .CH 2 .OH " C 6 H 5 .CO.OiHrC 6 H 5 .CO.OK. In order to effect this reaction it is necessary to employ a very concentrated solution of caustic potash, and allow the mixture to stand for several hours, taking care not to allow the tem- perature to rise too high. After diluting with water, the alcohol is removed with ether, and the acid is obtained from its aqueous solution. In the paraffin series this reaction gives resins and con- densation products. Like the aromatic aldehydes, glyoxal is reduced by alcoholic potash, giving glycollic acid. All the cases of oxidation which have been met with so far may be considered as a fixation of oxygen, or as a replacement by OH of a hydrogen united to carbon. It has not yet been possible to fix oxygen to the carbon in unsaturated compounds, OXIDATION. 25 with the exception of carbon monoxide. By passing a current of strongly ozonized dry air through anhydrous ether, ethyl peroxide is formed, C2H 5 .O.O.C2H 5 , a liquid which decomposes on heating, and reacts with water to form alcohol and hydrogen peroxide. The conversion of cyanides into cyanates presents an ex- ample of changing from the metallic radical into .OM, analo- gous to the transformation of H into .OH. If the transformation of alcohols into aldehydes, etc., how- ever, is not a simple removal of hydrogen, there are cases where oxygen causes the removal of hydrogen. The body then com- bines with itself; in this manner there are formed bisulphides, pinacones, etc., or a double linking is formed between two car- bon atoms. Thus, by passing the vapor of dibenzyl over heated lead oxide, stilbene is formed : r\ C 6 H 5 .CH 2 C 6 H 5 .CH Very probably an intermediate compound is formed at first which afterwards loses a molecule of water : C 6 H 5 .CH 2 C 6 H 5 .CH.;OH_ HO C 6 H 5 .CH I - I ! -^-> II C 6 H 5 .CH 2 C 6 H 5 .CH.!H C 6 H 5 .CH The hydrogen addition products of the aromatic hydrocar- bons can also lose their hydrogen by the action of oxidants, like fuming nitric acid, for instance, only, in place of obtaining the aromatic hydrocarbon, the nitro derivatives are produced: thus, C 6 H 4 (CH3)2.H 6 ,hexahydride of xylene,gives C 6 H.(N0 2 )3.(CH 3 )2. In the same manner the hydro-pyridine compounds lose hydrogen and pass into the pyridine derivatives. For ex- ample, piperidine, C 5 HnN, gives pyridine, C 5 H 5 .N; the hydro- chloride of conicine, CsHiyNCsH^H^N.He, gives propyl- pyridine, C 5 H 4 (C 3 H 7 )N. The removal of hydrogen from nitrogen compounds by oxi- 26 ORGANIC SYNTHESES. dation gives rise to a double linking between two carbon atoms, between a carbon and a nitrogen atom, or between two nitrogen atoms. 1 Thus, amarine, C 2 iHi 8 N 2 , gives lophine, C 2 iHi6N 2 , on oxidation with an acetic acid solution of chromic acid. These two bodies can be represented by the following formulas : C 6 H 5 .C.NH X C 6 H 5 .C.NH V || \CH.C 6 H 5 -^ || >C.C 6 H 5 . C 6 H 5 .C.NH/ C 6 H 5 .C.N ' The primary amines of the paraffin series, on oxidation with an alkaline solution of bromine, yield nitriles : R.CH 2 .NH 2 -- R.CfeN. These latter bodies may be converted again into amines by reducing agents. Without doubt, the removal of hydrogen from the amines takes place through the formation of an inter- mediate derivative, R.CH 2 .NBr 2 , which subsequently, by the action of the alkali, splits off 2HBr: ID RCH 2 .NH 2 - - R.CH 2 .NBr 2 -~> R.CN. The hydrazo derivatives are easily changed into azo-com- pounds : R.NH R.N R.NH R.N 1 The oxidizing action of the air converts para-phenylene-diamine, C 6 H 4 <^ J 4 j ]^{j 2 Al) N (1) C 6 H 3 /|2) NH 2 into tetra-amido-diphenyl-para-azophenylene, C 6 H/ }}' ^2 \/l\ >r ti\ n XT / ( o; iNi 2 (D JN (1) ^ 6 M 3 ^ (2) NH ^ Manganese dioxide and sulphuric acid, however, convert it into quinone, while, -with bleaching-powder, it gives quinone-dichloride; para-amidophenol is also oxidized in dilute solution by the air. OXIDATION 27 This may be brought about by the action of nitrous acid, mer- cury oxide, chlorine, bromine, ferric chloride, Fehling's solution, etc. In many cases simply atmospheric oxygen is sufficient. The hydrazines also give diazo derivatives; thus, the salts of phenyl-hydrazine, with mercuric oxide, are changed into the salts of diazo-benzene : C 6 H 5 .NH-NH 2 .HX 2H 2 = C 6 H 5 N = NX. In some cases, oxidation is accompanied by a hydration, especially with unsaturated compounds. One would think that in most cases the action of oxidizing agents in such bodies- would be to break up the double-linking; but from recent re- searches (principally those of Wagner) it would seem that these bodies, when oxidized by potassium permanganate, preserve the integrity of their molecule, and that the rupture is only due to the oxidation which is continued on the bodies formed in the first place. According to this, there would occur in unsaturated compounds the fixation of + H 2 0, that is to. say, the elements of hydrogen dioxide, or 2 (OH). 1 It is in this manner that the unsaturated hydrocarbons C TC H 2 n are transformed into glycols, and the unsaturated alcohols C n Hj n O into glycerols: CH 2 .OH CH 2 .OH CH 2 n , n CH 2 .OH CH + H 2 CH.OH CH 2 CH 2 .OH II ~* I CH 2 CH 2 .OH The yield of glycol is about 50 per cent, of the theoretic quantity; it may be increased by taking a weaker oxidant. This is the simplest manner of obtaining the higher glycols. 1 See Wagner, Action of Oxidants, etc. This kind of reaction is very simi- lar to that of A. Zaytzeff, who admits the formation of an oxide and the sub- sequent fixation of a molecule of water. It is known, besides, the oxygenated water (OH) 2 comb nes directly with ethylene, giving ethylenic glycol. 28 ORGANIC SYNTHESES. In the researches of Wagner, the method of procedure was as follows: 30 grams of the hydrocarbon are placed in a large flask with a litre of water, and vigorously agitated, while adding about 5 litres of a 1 per cent, solution of potassium perman- ganate. The proportions should be such that there is 1 atom of oxygen for 1 molecule of the hydrocarbon, and 1.5 to 2 atoms for higher numbers. The action of potassium permanganate on the hydrocarbons C n H 2n furnishes a good means of establishing their constitution. The oxidation of the alcohols C n H 2n O with potassium permanganate gives trihydric alcohols. The hydrocarbons, with two double bonds C n H 2n - 2 , as, for instance, diallyl, are con- verted into tetrahydric alcohols by reason of the fixation of 2 +2H 2 0=(OP) 4 . The unsaturated hydrocarbons and acids are easily changed into saturated acids by the action of potassium permanganate. A. Zaytzeff 1 has shown that oleic acid, CigH3 4 2 , is transformed into dioxy-stearic acid, Ci 8 H 3 4(OH) 2 2 . 2 From fumaric acid in the same manner is prepared tartaric acid. 3 The supposition may be made that in this transformation of unsaturated acids into saturated ones, for example, of palmi- tolic acid Ci 6 H 28 2 into oxy-palmitolic acid, Ci 6 H 28 4 , there is not a fixation of 2 , but a combination with (OH)4, accom- panied by a liberation of 2H 2 0. Wagner thus gives an explanation of the interesting fact of the change of non-symmetrical ethylene dibromide into brom- acetyl-bromide CH 2 Br.CO.Br, observed by Demole. . l Jour. Soc. Phys. Chim. Russe, vol. 17, p. 417. 2 Ibid., vol. 24, pp. 13-27. 3 S. Tanatar, On the Constitutional Formula of Fumaric and Oleic Acids. See Jour. Soc. Phys. Chim. Russe, vol. 13 (2), p. 256. OXIDATION 29 B. Direct Oxidation Accompanied by Decomposition of the Molecule. This series of reactions includes the influence of oxidants on tertiary alcohols, polyhydric alcohols, 1 ke tones, and many aromatic compounds. The oxidation of tertiary alcohols takes place with fixation of + H 2 0; the two groups which are the richest in hydrogen remain in combination with the C.OH group, while the third radical is split off and is subjected to a further oxidation. Thus, in the oxidation of trimethyl-carbinol there is obtained acetone and carbon dioxide : CH 3 \ /|CH 3 OH +0 3 -2H 2 == CH 3 \ C0 2 CH 3 /^\OH + OH - H 2 CHa/*' 4 Dimethyl-ethyl-carbinol, under the same conditions, gives acetone and acetic acid: (CH 3 ) 2 C.OH OH -H 2 (CH 3 ) 2 .CO ..... I ..... + CH 2 .CH 3 OH + 2 -H 2 CH 3 .CO.OH with isopropyl-dimethyl-carbinol; two molecules of acetone are obtained: .C.OH OH - H 2 = (CH 3 ) 2 CO. -H 2 = (CH 3 ) 2 CO. The acid-alcohols behave in the same manner as the tertiary alcohols. /OTT Thus, with the tertiary acid-alcohol, R 2 C<^ QQQ jj> the ketone 1 Prjibuitek, On Some Oxidation Products of the Polyatomic Alcohols. St. Petersburg, 1881 (in Russian). By the oxidation of erythrite with potassium permanganate, oxalic acid was obtained. 3 ORGANIC SYNTHESES. COOH' the aldehyde R.CHO is formed: R 2 .C.OH OH - H 2 = R 2 .CO I + CO.OH OH-H 2 = C0 2 :Nc.OH OH - H 2 = R.CH.O X l + CO.OH OH-H 2 = C0 2 Certain acids of the preceding general formula are sometimes oxidized and still preserve the integrity of their molecule. The decomposition of the unsaturated hydrocarbons by the action of oxidants is merely the result of a further oxidation of the first products formed. Bv fusing with caustic potash, for instance, some of the acids of the acrylic series undergo an oxidation simultaneous with their reduction. Also, isobutylene on oxidation gives a glycol, which further yields an hydroxy- acid, and the latter is decomposed into a ketone and an acid: (CH 3 ) 2 .C OH (CH 3 ) 2 .C.OH (CH 3 ) 2 .C.OH II + > I CH 2 OH + 2 -H 2 CH 2 .OH CO.OH (CH 3 ) 2 C. OH .OH-H 2 (CH 3 ) 2 .CO CO.OH 'OH-H 2 C0 2 If the oxidation takes place in the presence of an acid, a glycol is formed, which then loses a molecule of water, and by a further oxidation gives abnormal products. Cinnamic acid, C 6 H 5 .CH:CH.COOH, for example, should give at first, on oxidation, a di-acid alcohol, and this latter body is subsequently converted into benzaldehyde and glyoxylic acid: OXIDATION. 31 C 6 H 5 . CH C 6 H 5 . CH.OH C 6 H 5 .CHO COOH.CH HOH COOH.CH.OH OH CH(OH) 2 .COOH These finally are converted by oxidation into benzoic acid and oxalic acid. These reactions serve as a means of detecting the presence of cinnamic acid, it being recognized by evolving the odor of benzaldehyde when heated with Pb02. It might be noted that this method of oxidation frequently causes a division of the molecule. 1 Glycol, for instance, in dilute alka- line solution, when treated with lead peroxide, gives formic acid with a simultaneous evolution of hydrogen gas : CH 2 .OH PKn H.COOH I rPU 2 , TT -- > +Jti 2 . CH 2 .OH H.COOH Alcohol, cane-sugar, and other such compounds behave in a similar manner, yielding the same products: CH 3 PKn H.COOH | _L^L 2 _> +H 2 . CH 2 .OH H.COOH Ortho-nitrobenzaldehyde may be conveniently prepared from cinnamic acid. The solution of the latter is poured into benzene, and there is added with constant stirring a dilute solution of potassium permanganate. The aldehyde at first formed passes into solution in the benzene, and is thus preserved from further oxidation. This, in fact, is a good general method for protecting easily oxidizable products from being decomposed by successive oxidation. After each addition of the oxidant, the liquid should be well shaken or stirred, in order to remove the aldehyde as much as possible from the further oxidizing influence of the potassium permanganate. 1 Thus uric acid gives allantoin. 32 ORGANIC SYNTHESES. Ke tones are oxidized with hydrolysis; that is to say, there is a fixation of + H 2 = (OH) 2 . For example : CHg.CO 1 _J. OH CH 3 .CO.OH CH 3 .CH 2 CH 3 .CO | _|_ OH + 2 -H 2 CH 3 .CO.OH OH CH 3 .CO.OH (CH 3 ) 2 .CH (CH 3 ) 3 .C.CO 1 _i_ OH + 0-H 2 (CH 3 ) 2 .CO OH (CH 3 ) 3 .C.CO.OH 1 ' CH 3 OH + 2 -H 2 H.CO.OH The oxidation of ketones is a more complicated reaction than would at first sight appear. 1 In fact, the products which are obtained are dependent upon the nature of the oxidant and the circumstances of the reaction. Thus, with chromic acid mixture, there is usually obtained, not two, but four, compounds; the decomposition taking place in two different directions, on account of the oxidation of the two CH 3 groups attached to the CO. We have a proof of it in the oxidation of ethyl-isobutyl-ketone : the principal products formed are acetic and isovaleric acids, while, at the same time, prop^onic and isobutyric acids are produced : \ + OH+0 2 -H 2 0-CH 3 .CO.OH (CH 3 ) 2 CH.CH 2 +OH = (CH 3 ) 2 .CH.CH 2 .CO.OH CH 3 . CH 2 \ m +OH _ =CH 3 .CH 2 .CO.OH U \ > t 6 il4< p CH XXXOH \CO The best oxidant to employ is a chromic acid mixture : the acetic acid solution of chromic acid gives principally the naphtho- quinone CioH 6 2 . Quinoline, C4H 4 .C 5 H 3 N, behaves hke naph- thalene and gives pyridine dicarboxylic acid (COOH) 2 .C 5 H 3 N. It has been shown that in the oxidation of aromatic hydro- carbons, the groups C n H2n+i, like CH 3 , are converted into carboxyl, COOH; the group C 6 H 5 behaves in a like manner, and thus diphenyl gives benzoic acid: C 6 H 5 .C 6 H 5 -^- C 6 H 5 .CO.OH. The oxidation of additive hydrogen aromatic compounds gives some interesting results: quinic acid, C 6 H 7 (OH) 4 CO.OH, with manganese dioxide and sulphuric acid, is converted into qui- OXIDATION. 35 none; it was in this manner that the latter was discovered by Woskresenky. 1 The hydrochloride of a-tctra-hydro-naphthyl- amine, NH 2 .C 10 H 7 .H4 ; with permanganate, gives adipic acid, 6 Hi 4 (yield, about 18 per cent). Benzene with potassium chlorate and sulphuric acid gives j3-trichlor-acetyl-acrylic acid, CC1 3 .CO.CH=CH.CO.OH (also called trichlor-phenomalic acid), which has been wrongly taken for trichlor-hydroquinone. The azo derivatives are oxidized with a decomposition of their molecule. It is probable that azo-benzene, C 6 H 5 N: N.C 6 H 5 , 2 heated for some time in a sealed tube with an acetic acid solution of chromic acid, is converted into nitrobenzene, C 6 H 5 .N0 2 (?). 3 IV. INDIRECT OXIDATION. A. Substitution of a Halogen by the Hydroxyl Group. 4 This reaction, which results in the formation of an alcohol, may be brought about by the action of water alone; generally it is necessary to heat in a sealed tube. If the alcohol formed is soluble in water, it may be isolated by means of potassium carbonate. Tertiary compounds more easily give up the halogen than do the secondary compounds; and these, in turn, more readily than the primary compounds. 1 A. Woskresensky, On Quinic Acid and the Discovery of a New Product, Quinone, St. Petersburg, 1839 (in Russian). 2 Petrieff, Data for the Study of Azo-Benzene, Odessa, 1872 (in Russian). 3 See Jour. Soc. phys. Chim. Eusse, vol. 18, p. 387. 4 The conversion of primary alcohols into aldehydes by the oxidizing action of chlorine is no doubt an indirect reaction, there first being a substitution of hydrogen by chlorine and then a subsequent splitting off of hydrochloric acid: I > CH 3 .CH:0+HC1. The formation of chloral from ethyl alcohol may be explained in this way, there also occurring a simultaneous substitution of the hydrogen of the CH 3 group by chlorine. 36 ORGANIC SYNTHESES. For example, tertiary amyl iodide is easily converted into the corresponding alcohol by agitation with cold water : (CH3)2.(C 2 H 5 )C.I JMU (CH 3 )2(C 2 H 5 ).C.OH. Triphenyl-brom-me thane, (C 6 H 5 ) 3 .C.Br, behaves in the same manner. Isopropyl iodide, (CH 3 ) 2 ,CHI, however, is only con- verted into isopropyl alcohol, (CH 3 ) 2 .CH.OH, after a long heating under pressure with a large quantity of water. And the conversion of isobutyl iodide (CH 3 ) 2 :CH.CH 2 I, or of primary isoamyl chloride (CH 3 ) 2 CH.CH 2 .CH 2 .C1, takes place with even greater difficulty. Isobutyl iodide, however, with silver oxide and water, instead of giving the corresponding alcohol, gives tertiary butyl alcohol. This method of obtaining alcohols is only applicable in cases where the halogen compound does not easily form an unsaturated body through the splitting off of hydrochloric acid. In all cases, however, it is best to use an excess of water in order to prevent the formation of an unsaturated body. For instance, a-hexyl iodide with a small amount of water gives hexylene and hydriodic acid; with a large excess of water r it furnishes the alcohol, CH3.(CH 2 )3.CH.(OH)CH 3 . Some- times, secondary products are formed; on heating ethyl bromide with a little water to 200 C., ethyl oxide is formed, at the same time as ethylene, C 2 H 4 , and hydrobromic acid, from the further action of the ethyl bromide on the alcohol. In decomposing the iodides, sealed tubes may be avoided by the use of oxides (PbO, Ag 2 0, HgO), barium hydrate (Ba(OH) 2 ), or the carbonated alkalies, K 2 C0 3 and Na 2 C0 3 . Silver oxide is particularly good for those iodides which easily give unsaturated compounds, for the reaction then takes place without the necessity of heating. The other hydrates and carbonates only act well on boiling, and always lead to the formation of unsaturated compounds. In certain cases, when, these latter cannot be formed, the substitution of a halogen by OH is effected by the aid of the hydrates of the alkaline metals.. OXIDATION. 37 pyrocatechol. It often happens in these fusions with potash that there is a molecular transformation, either by reason of too prolonged an action or too high a temperature. The ortho- and meta- bromphenols, when fused with potash, both give pyrocatechol and resorcinol, CeEL^ / J QJJ- The alkali during the fusion behaves at times as a reducing agent and again as an oxidant; and thus it is possible to explain the molecular transposition by two successive reactions of oxidation and reduction. The ortho-bromphenol, C 6 H 4 <^ L) Br> is at first transformed into OXIDATION. 39 /(I) OH 6 H 3 (-(2) Br , and then into resorcinol. C 6 H 4 < )i< Xti. \3) OH The presence of the N0 2 group facilitates the exchange of halogens with OH, especially when the two substituents are in the ortho (1:2) or meta (1:3) positions. In the latter case the influence is so great that the nitro-chlor-benzene, C 6 H 4 and saturate with a current of N 2 3 gas; on adding a cold concentrated solution of mercuric chloride, HgCl 2 , a double compound of mercury separates out, which is subsequently decomposed by boiling with water until nitrogen ceases to be evolved. Soda is added; the oxide of mercury is filtered off; the filtrate is acidu- lated, and the chlor-phenol is separated by dissolving in ether. The same method of making phenols may also be used in the preparation of oxy-phenols, the chlor- and nitre-derivatives,. 42 ORGANIC SYNTHESES. the oxy-aldehydes, oxy-ke tones. Certain of the brom- and chlor-amines present exceptions to the usual procedure, the NH 2 being replaced by H instead of OH. Thus, the diazo- /(2) Br compound of dibrom-anilLne, C 6 H 3 ^-(1) NH 2 , when decom- \(4) Br posed by boiling with water, gives di-brom-benzene; the /(I) CH 3 chlor-toluidine, CeH 3 ^-(3) Cl , in place of chlor-cresol gives \(4) NH 2 /"TT * chlor-toluene, Ce^ / ^ The NH 2 group in acid amides of amido-carboxyl and .amido-sulphonic acids is very resistant to the action of nitrous acid, N203. 1 Thus, the amides of the meta- and para-amido- benzoic acids, CeH^ ^Q ^TTT , through the medium of the diazo reaction, are converted into CeEUQQ^jj , but the group CO.NH.2 remains unchanged; the amide of the ortho-amido- sulphonic acid of benzene, CeEL J 2 , behaves in the same way. If a very negative element or radical occurs with the NH 2 group, the latter, by the action of alkalies, is often converted into OH with the elimination of ammonia. Many aromatic amido compounds in which the NH 2 is in the ortho- or para- position to N0 2 behave in this manner. For example, para- jiitro-aniline, C 6 H4 4 < NQ . 1 If there is no NH 2 group in the aromatic nucleus, then it is the SO 2 -NH 2 group which is attacked by the nitrous oxide. Thus: 2 conTCrted into C H <(3) f.OH OXIDATION. 43 The NH 2 group when joined to CO, is easily converted into OH by the action of acids or alkalies. The acid amides are thus changed into carboxylic acids. Formamide with concen- trated caustic potash, even in the cold, gives potassium formate with liberation of NH 3 . In other cases it is necessary to boil with the alkali for a prolonged time in order to liberate all of the ammonia. In place of potash, soda may be used, or even barytes or caustic lime. The NH 2 group in acid amides is converted into OH by the action of nitric acid. Thus, CH 3 .CO.NH 2 + N0 2 .OH = CH 3 .CO.OH + N 2 + H 2 0. Substituted acid amides, such as methyl-acetamide, behave in the same manner. By the action of nitric acid on dimethyl-acetamide, there is formed, at the same time with the acetic acid, dimethyl- nitramine : The amides of the di-acids, by the action of boiling ammonia, are converted into the amido-ammonium salts. For example: CO.NH 2 CO.NH 2 I I CO.NH 2 CO.ONH 4 Oxamide. Ammonium oxamate. If alkalies act but slowly on acid amides, they may be heated in a sealed tube with concentrated hydrochloric acid. With the keto-amides R.CO.CO.NH 2 , however, it is necessary to operate with caution, for they are easily decomposed: (CH 3 ) 2 .CH.CO.CO.NH 2 , by the moderate action of hydro- chloric acid, furnishes, simultaneously with the acid, (CH 3 ) 2 . CH.CO.CO.OH, considerable iso-butyric acid, (CH 3 ) 2 .CH.COOH. The amides of sulphonic acids, on treatment with hydro- chloric acid at 150 C., are converted into sulphonic acids; if the reaction is energetic it may even happen that the S0 2 .OH group is removed. The S0 2 NH 2 group is very resist- ant to alkalies. 44 ORGANIC SYNTHESES. The transformation of >N.OH into O takes place by the action of concentrated hydrochloric acid on the iso-nitroso- compounds and aldoximes, heating if necessary; a weaker acid, such as acetic, may also be used: CH 3 .C=N.OH CO.CH 3 | + H 2 = | +NH 2 .OH CH 2 .CH 2 .CO.OH CH 2 .CH 2 .CO.OH 7-iso-nitroso-valeric acid. ^-acetyl-propionic acid. Iso-nitroso bodies are decomposed in the same manner by the action of amyl nitrite : C 6 H 5 .CO.CO.CH 3 + C 5 Hi !.OH + N 2 0. The transformation of >NH into takes place sometimes by the action of water at ordinary temperatures, and also on heating with dilute acid. The imido-ethers (action of alcohols on nitriles) are decomposed very easily : HCO.OC 2 H 5 Ethyl-imido-fonnate. Ethyl formate. The nitriles may be converted into esters of the acids through the means of imido-ethers. Benzoyl-formic ester is easily prepared by passing hydrochloric acid into a cold solution of benzoyl cyanide, C 6 H 5 .CO.CN, in alcohol. The liquid is allowed to stand for several days, and the ester is separated with water. The conversion of guanidine into urea by the action of boiling baryta- water is another example of the change of NH into 0. The transformation of N = N into H and OH is brought about by prolonged boiling with water of the esters of the diazo acids N / of the paraffin series. The ester of diazo-acetic acid, HC\ , N gives the ester of gly collie acid. f C0 OXIDATION. 45 C. Conversion of the Sulphonic Acid Group into the Hydroxyl Group. 1 This reaction, which is often employed in the aromatic series, is brought about by the fusion of the sulphonic acids with caustic potash, followed by decomposition by an acid : C 6 H 5 .S0 2 .OK + 2KOH = C 6 H 5 .OK + K 2 S0 3 + H 2 0. The sulphonic acid is heated in a silver or nickel crucible by vapor of naphthalene or anthracene with solid caustic potash to which is added a little water. The time of the fusion varies from several minutes to several hours, and the temperature varies from 160 to 300 C. The yield of the phenol increases with the temperature and the amount of alkali. With 6 mole- cules of KOH on C 6 H 5 .S0 2 .OK and heating for 1 hour, a yield of 94 per cent, of the theoretical may be obtained. The exact time of stopping the fusion cannot always be easily recognized. When the reaction is finished, the mass is broken up and dis- solved in water and acidulated; if nothing separates out, extract with ether. Instead of using the free sulphonic acid, the lead salt may be employed, which is often prepared in order to purify the acid. When an aromatic body is fused with potash in the presence of an oxidizing body, there may occur the oxidation of a hydrogen in the nucleus. In this manner the hydroxy- anthraquinones (alizarins) may be prepared. If there are two sulphonic acid groups in the same molecule, by using suitable precautions a single one may be substituted; if the reaction is very energetic, both will be attacked: H /(I) S0 2 .OH Uil4 \(3) S0 2 .OH' Benzene-disulphonic acid. 1 This is equivalent to the replacement of H by OH through the medium of the sulphonic acid derivatives. 46 ORGANIC SYNTHESES. at 170-180 .0., is converted into r TT /(I) S0 2 .OH UM4 \(3) OH Phenol-sulphonic acid. Frequently fusions with potash lead 10 molecular trans- positions. With the acid (para-phenol-sulphonic acid), OTT resorcinol, CeH^ /i^ QTT, is obtained, which is a meta-product. This peculiarity may be explained by two successive reac- tions, oxidation and reduction (see above). The CH 3 group is sometimes oxidized by fusion with potash: r H (1) CH 3 . p R /(I) CO.OH V^6*l4/o\ Grk nTT gives U6-tl4\ / \ /^TT (Z) ovJ 2 .Ul \\^) v/Xl Ortho-toluene-sulphonic acid. Ortho-oxybenzoic acid. Soda may be used instead of potash; but, as its action is not so energetic, it is necessary to prolong the time of fusion at a higher temperature. D. Displacement of Sulphur by Oxygen. This substitution (exchange of two valences of the carbon atom) is readily effected by the oxides or salts of the heavy metals (PbO, HgO, AgN0 3 , ammoniacal solution of a silver salt, etc.), and sometimes also by alkalies. Thus, thiophenyl-urea gives phenyl-urea, 'NH2 m /NH 2 ,NH.C 6 H 5 ^XNH.CeHs' by boiling the aqueous or alcoholic solution with PbO, or freshly precipitated HgO. With silver nitrate, the reaction is not always complete, intermediate compounds being formed. With allyl-thio-urea, OXIDATION. 47 for instance, there is first formed C^x^i^G H .AgN0 3 , which, on moderately heating with AgN0 3 , is decomposed into +Ag2S+2HN 3; this being kept neutral b y adding baryta-water from time to time. The dithionic acids, like C 6 H 5 .CS.SH, lose S on boiling with an alcoholic solution of potash. Oxidations which take place with the fixation of water will be taken up under Chapter V. CHAPTER II. REDUCTION. I. GENERAL CONSIDERATIONS. REDUCTION is the opposite of oxidation. It may occur in several different forms : (1) Reduction of hydroxyl oxygen, as, C 6 H 5 .OH + H 2 = C 6 H 5 .H + H 2 0. Phenol. Benzene. (2) Reduction of ketonic oxygen to hydroxyl: CH 3 .CH : + H 2 = CH 3 .CH 2 .OH. Aldehyde. AlcohoL (3) Reduction of unsaturated groups: CH 2 II +H 2 = CH 2 Ethylene. Ethane. CH 3 .C : N + 2H 2 = CH 3 .CH 2 .NH 2 . Methyl cyanide. Ethylamine. (4) Reduction of halogen compounds: CH 2 (C1) .CO.OH + H 2 = CH 3 .CO.OH + HC1. Chlor-acetic acid. Acetic acid. (5) Reduction of nitro derivatives: C 6 H 5 .N0 2 + 3H 2 = C 6 H 5 .NH 2 + 2H 2 0. Nitrobenzene. Aniline C 6 H 5 .N X C 6 H 5 NH | >0+2H 2 = | +H 2 0. C6H5.N/ C 6 H 5 NH Azoxyoenzene. Hydrazobenzene. 48 REDUCTION. 49 (6) Reduction attended by a decomposition of the molecule:, thus, the phenylhydrazine compound of acetaldehyde, when reduced with sodium amalgam, gives rise to two separate amines, aniline and ethylamine : CH 3 .CH = N.NH.C 6 H 5 + 2H 2 = C 6 H 5 NH 2 + CH 3 .CH 2 .NH 2 . II. ACTION OF REDUCING AGENTS. Though the most logical reagent for reduction purposes would be hydrogen in its nascent condition, yet it does not appear to have met with success as a reducing agent for organic compounds. Attempts have been made, however, to employ clectrolytically prepared nascent hydrogen, but the results have not been gratifying. By using this means, Haussermann, 1 in act- ing on nitrobenzene dissolved in alcoholic caustic soda, obtained hydrazo-benzene and benzidine sulphate; aniline was only pro- duced when a cathode of zinc, instead of platinum, was used. The majority of reactions involving the reduction of organic compounds take place indirectly through the use of various reducing agents, of which the following are the most important : Hydriodic acid is probably the strongest reducing agent employed in connection with organic compounds. Its action depends on the readiness with which it decomposes into free iodine and hydrogen; it may be employed dissolved either in water or in acetic acid. According to Berthelot, who was the first to recognize its reducing action on organic substances, hydriodic acid is capable of reducing every organic compound to the limit hydrocarbon containing the same number of carbon atoms. He recommended heating the substance to be reduced with a large excess of hydriodic acid in a sealed tube for several hours at a temperature of 275 C. The action of hydriodic acid may be considerably accelerated by the addition of phosphorus, 2 1 Chem. Zeit., 1893, p. 129. 2 The increased efficiency of the hydriodic acid due to the addition of phos- phorus may be accounted for by the fact that the phosphorus combines with the free iodine liberated in the reduction to form phosphorus iodide; and the 50 ORGANIC SYNTHESES. which also has the advantage of preventing the formation of undesirable by-products. It is probable that, in the reaction between phosphorus and hydriodic acid, phosphonium iodide is formed as an intermediate step in the reduction. By the use of phosphorus and hydriodic acid, it is possible to carry out a large number of reductions without the necessity of heating in a sealed tube, simply boiling the compound to be reduced with strong hydriodic acid in a flask connected with an inverted condenser and adding fragments of phosphorus from time ta time. 1 For some reductions yellow phosphorus is required^ while, for others, red phosphorus may be used. In cases where very energetic reduction is necessary, however, recourse must be had to the method of heating the mixture in a sealed tube to a high temperature, and with a large excess of hydriodicr acid. 2 Sodium and sodium amalgam are largely employed as reducing agents, as they are very efficient and may be applied conveniently. Sodium is mostly used in connection with an alcoholic solution of the substance to be reduced, though, at times, either water or ether may be employed as the solvent. There appears to be a considerable difference in the action of sodium as a reducing agent, depending on the nature of the alcohol employed as the solvent; when amyl alcohol, for in- stance, is used as the medium, the reducing power of the sodium appears to be greater than with ethyl or methyl alcohols. Sodium amalgam is less energetic in its action than sodium. An latter in the presence of water (also generally present as a by-product in the reduc- tion) further reacts to give hydriodic and phosphorous acids. So, in reality, by the intervention of the phosphorus, the iodine is used over and over again to effect the reduction; while at the same time the phosphorus also removes the water, the presence of which would soon limit the reaction, or cause the forma- tion of secondary products: PI 3 + 3H 2 O= 3HI+ HgPOg. 1 In this manner iodoform, CHI 3 , may be reduced to methylene iodide, CH.jI a (see Baeyer, Berichte, vol. v, p. 1095). 2 By employing this method of reduction, anthracene, C I4 H 10 , may be reduced to the hydrocarbon C, 4 H M . (See Lucas, Berichte, vol. xxi, p. 2510). REDUCTION. 51 amalgam containing about 2J- per cent, of sodium is generally employed, as this is solid and may be readily pulverized. Sodium amalgam is most efficient when used in the presence of carbon dioxide, and it may be employed in alcoholic, ethereal, or acetic acid solutions. As sodium hydrate is formed in the course of the reaction with sodium amalgam, the efficiency and speed of the reduction may be increased by neutralizing the alkali with acids. Metallic tin and stannous chloride are also employed exten- sively as reducing agents. Tin itself is principally used in connection with hydrochloric acid, and the metal is afterwards removed by precipitation with hydrogen sulphide. Stannous chloride is used in acid solution, and, as it is soluble in alcohol, it may be conveniently employed with this solvent; it may also be used with glacial acetic acid. Sometimes an alkaline solu- tion of tin (sodium stannite) is employed for reductions. This solution is best prepared by adding powdered stannous chloride to a strong solution of sodium hydrate until a precipitate begins to form. Zinc may be employed for the reduction of organic com- pounds in either acid or alkaline solutions, and at times even in neutral solution. Zinc dust when used at high temperatures is a powerful reducing agent; even when boiled with water, zinc dust is capable of reducing many substances. III. SUBSTITUTION OF HYDROGEN FOR HYDROXYL OR OTHER ELEMENT, GROUP, OR RADICAL. A. Reduction of Hydroxyl and Ketonic Compounds. (i) Reduction of Acids. In certain cases acids are converted into aldehydes by displacing the OH group with H. Benzoic and oxy-benzoic acids behave in this manner. The first, on treatment with sodium amalgam in the presence of water, gives benzaldehyde; but the second one is converted into the corresponding alcohol. The indirect method which would lead 5 2 ORGANIC SYNTHESES. to the same result consists in heating the salt of the acid with a formate, or in reducing the chlorides or anhydrides of the acids. In the latter case, by an energetic reduction, the corre- sponding alcohols may be obtained. 1 The reduction of succinyl chloride, however, with sodium amalgam and acetic acid, does not appear to give the corresponding aldehyde, but the lac tone of ^-oxy butyric acid. Phthalyl chloride behaves in the same manner. Under the influence of more energetic agents, such as hydriodic acid, acids are converted into hydrocarbons by conversion of the CO. OH group into CH 3 . Thus, stearic acid, Ci8H 36 2 , gives a hydrocarbon, Ci 8 H 38 , and benzoic acid, C 7 H 6 2 , gives toluene, C 7 H 8 . According to Berthelot, reduction by means of hydriodic acid takes place in the following manner : The acid to be reduced is heated on an oil-bath to 200-280 C.with 20 to 30, or even 100 times its weight of hydriodic acid (sp. gr. = 1.8 to 2). The tubes are opened from time to time in order to allow of the escape of gas, which may be collected over mercury when it is desired to analyze it. On account of the great pressure which exists in the tubes, they must be opened in a very careful manner. The reduction of the fatty acids, and of products obtained by the action of phosphorus pentachloride on ketones, according to Kraft, takes place in the following manner: In each tube there is placed 2 to 4 grams of the acid, together with 2 to 4 times the quantity of hydriodic acid (sp. gr. = 1.7) and J part of red phosphorus; the tubes are heated for 3 to 5 hours at 210-240 C., after which they are opened. A small amount of phosphorus is added, and the tubes are reheated to- 210-210 C. These operations are repeated two or three times, and finally water is added to decompose the iodide of phosphorus which is formed. The hydrocarbons are distilled in steam, and then heated with a solution of caustic alkali. But little is known concerning the reduction of acid amides and imides. Sodium amalgam with acetamide gives a small 1 See Zaytzeff, A New Method for the Conversion of Aliphatic Acids into the Corresponding Alcohols, Kagan, 1870 (in Russian). REDUCTION. 53, quantity of alcohol. The action of sodium in amyl alcohol on phthalimide reduces the two CO groups: CH 2 .NH 2 (2) Reduction of Aldehydes. Aldehydes are converted into alcohols by the action of sodium amalgam in an acidulated (H 2 S0 4 ) aqueous solution; the alcohol so formed is separated by distillation, the distillate being further treated with potas- sium carbonate. The higher aldehydes of the aliphatic series, which are difficultly soluble in water, are reduced by the use of zinc dust in glacial acetic acid solution; in this case, however, the reaction results, not in the formation of the alcohol, but of the corresponding acetic ester, which must be saponified in order to obtain the alcohol. Derivatives of chlor-substituted aldehydes, such as chloral, are reduced to the corresponding alcohols by zinc ethyl; thus r chloral gives tri-chlor-alcohol. In order to reduce aromatic aldehydes it is necessary to suspend them in water or dissolve them in dilute alcohol. 1 For the reduction, an alcoholic solu- tion of potash may be used: 2C 6 H 5 .CHO + KHO = C 6 H 5 .CH 2 .OH + C 6 H 5 CO.OK. The aromatic aldehydes are also converted into amines by the action of ammonium formate; for example, the conversion of benzaldehyde, C 6 H 5 .CHO, into benzylamine, C 6 H 3 .CH 2 .NH 2 . By the prolonged action at 130-150 C. of a concentrated solution of hydriodic acid and red phosphorus, aldehydes are converted into hydrocarbons (substitution of CHO by H 3 ) : C 6 H 5 CHO - - C 6 H 5 CH 3 . 2 (3) Reduction of Ketones and Quinones. The conversion of the CO group into CH.OH or C.OH, and the production of 1 The aromatic aldehydes are liable to form condensation products. 2 For the action of halogen acids on methylene oxide, see Jour. Soc. Chim. Russe, vol. 19, p. 169. 54 ORGANIC SYNTHESES. alcohols and phenols by the aid of ketones and quinones, takes place by the action of sodium, or its amalgam in the presence of water, by boiling with a solution of alcoholic potash in the presence of zinc powder, and even by the action of sulphurous acid. Quinone, CeHiC^, is readily converted into hydroqui- none; so much so, in fact, that, in an alcoholic solution under the influence of sunlight, the quinone changes the alcohol into aldehyde. The ketone, dissolved in ether or benzene, is placed in a flask with water; there is then added small shavings of metallic sodium, which maintain themselves between the two liquids. It is usually necessary to moderate the energy of the reaction by cooling. When the odor of the ketone has disappeared, the upper layer of liquid is removed, and the alcohol produced is isolated by crystallization or distillation. There are also formed condensation products. The ke tonic acids behave like the ketones; thus, pyruvic acid gives lactic acid with sodium amalgam in the presence of water : CH 3 .CO.CO.OH + H 2 = CH 3 .CH(OH) .CO.OH. In order to avoid the decomposition of certain ketonic acids by the alkali, it is necessary to keep the temperature from rising too high, and to neutralize from time to time with an acid. In certain cases, by the reduction of ketonic acids, there are formed lac tones in place of oxyacids; and some- times the latter, which may be formed at first, are reduced in their turn. For instance, benzophenone-meta-carboxylic acid, C 6 H5.CO.C 6 H4.CO.OH, with sodium amalgam, is con- verted into benzo-hydroxy-meta-carboxylic acid : C 6 H 5 .CH(OH).C 6 H4.COOH, and C 6 H 5 .CH 2 .C 6 H 4 .CO.OH. The conversion of the CO group into CH 2 , and the formation of hydrocarbons with the aid of ketones, is brought about by the action of hydriodic acid under the same conditions as for REDUCTION. 55 aldehydes, or by distillation with zinc dust. Thus, benzophc- none, (C 6 H 5 )2CO, gives diphenylme thane, (Cel^.CHo. 1 (4) Reduction of Alcohols. The reduction of alcohols (con- version of OH into H) usually takes place in an indirect manner. The reduction of phenols (such as the conversion of phenol, C 6 H 5 OH, or of pyrogallol, C 6 H 3 (OH) 3 , into C 6 H 6 ) is brought about by distillation with zinc dust or with phosphorus pentasulphide. Oxypyridine and quinoline are also reduced with zinc dust. Cuminic alcohol, C 6 H 4 / ^^ 2 ' on dis " tillation with zinc dust, gives cymene, C 6 H 4 <^ CH 2 .CH 2 .CH 3 . Certain reductions of aromatic alcohols are accompanied by an oxidation : benzyl alcohol, with alcoholic potash, gives toluene and benzoic acid. The simple ethers of aromatic alcohols are separated by heat into aldehydes and hydrocarbons; benzyl ether gives benzaldehyde and toluene : C 6 H 6 .CHO. Hydriodic acid and red phosphorus, on heating, furnish a good means of reduction for alcohols of the paraffin series, as well as those of the aromatic series having the OH in a side chain, and also oxy acids. Aromatic lac tones or phthaleins are also reduced with zinc powder in alkaline solution, and yield phthalines. Ethylene oxide is readily converted into alcohol with sodium amalgam: 2V CH 2 .OH. I >+H 2 =j CH/ CH 3 This reaction may be considered as a reduction followed by a fixation of water. The reverse reaction reduction with 1 The keto-phenone, C 6 H 6 CO-CH 3 , treated with hydriodic acid, does not give ethyl-benzene, CJHgCgHi, but condensation products. 5 6 ORGANIC SYNTHESES. elimination of water is effected by boiling polyatomic alcohols with formic acid. There is at first formed a monoformin, which is decomposed with liberation of water and carbon dioxide; it is in this manner that allyl alcohol is prepared from glycerin. Ketonic aldehydes, with zinc dust in acetic acid solution, suffer reduction of their hydroxyl group, but in alkaline solu- tion the CO group is reduced. For example, benzoin, in the first case, is transformed into desoxybenzoin, 1 and, in the second case, into hy droxy benzoin : CO.C 6 H 5 CO.C 6 H 5 HO.CH.C 6 H 5 I > I or HO.CH.C 6 H 5 CH 2 .C 6 H 5 HO.CH.C 6 H5 B. Substitution of Other Groups by Hydrogen. (i) Substitution of the Halogens. This substitution is brought about by the action of a large number of reducing agents : sodium amalgam in the presence of water, metals in the presence of acids, zinc dust with alkali, hydriodic acid alone or in the presence of red phosphorus. The last reagent is very ener- getic. Thus, C 8 Hi 7 .C(Cl 2 ).CH3, heated in a sealed tube with this mixture, is completely converted into decane, Ci H 2 2. In order to substitute iodine with hydrogen, the zinc-copper couple may be used with advantage. This is, in fact, the best means of preparing methane: into a vessel furnished with a zinc-copper couple there is led an alcoholic solution of methyl iodide. The flask is then closed with a cork furnished with an escape-tube, and heated gently on a water-bath. The gas is given off, and, by properly regulating the temperature, a slow 1 Desoxybenzoin (phenyl-benzyl-ketone), with reducing agents, furnishes partly the corresponding pinacone and partly the secondary alcohol, which, under the influence of acetic acid, loses a molecule of water and gives the hydrocarbon: C 6 H 5 .C-OH C 6 H 5 .CH-OH C 6 H,-CH 2 I > \ + || . C 6 H 5 CHj C 6 H 5 CH 2 C 6 Hj CH Pinacone. Alcohol. REDUCTION. 57 and regular current may be obtained containing only a small quantity of the vapors of alcohol and methyl iodide. Two c.c. of CH 3 I give 700 c.c. of CH 4 . The reaction may be ex- pressed as follows : CH 3 I + Zn + H 2 = Zn/ + CH 4 . In order to replace halogens in an aromatic nucleus, it is necessary to use sodium amalgam in the presence of water, or hydriodic acid with phosphorus in sealed tubes. Metals with acids react but seldom and very slowly; while, on the contrary, the halogens in side-chains are displaced very easily. Chlorine in the pyridine nucleus is removed by tin and hydrochloric acid: C 5 H 3 N(C1).CO.OH --- > CsHtN.CO.OH. Chlor-nicotinic acid. Nicotinic acid. Also, in the chlorides of organic acids, the halogen is easily replaced. The chlorides of the sulphonic acids behave in a similar manner: thus, R.S0 2 C1 is converted into R.S0 2 H. The reduction should take place in an alkaline solution; in acid solution the reduction goes still further, and a mercaptan is formed, R.SH. Sometimes the reduction is accompanied by a decomposition of the molecule; chlor-sulphocymene, CioH 7 , S0 2 .C1, with sodium amalgam, gives Ci H 8 and S0 2 . It is easy to remove bromine when combined with oxygen in derivatives, as in phenol bromide, C 6 H 5 .OBr. Tribrom- phenol-bromide, CeB , loses bromine on boiling with alcohol, giving tribrom-phenol, Several halogen atoms may be replaced successively in the combinations in which they occur. In compounds of the paraffin series, if the halogens occur with neighboring carbon atoms, instead of a simple replacement of the halogen, there is generally a rupture of the molecule, with the formation of unsaturated compounds. On partial reduction with hydriodic $8 ORGANIC SYNTHESES. acid, for instance, propylene chloride, CH 3 .CH(C1).CH 2 C1, gives isopropyl chloride, CH 3 .CHC1.CH 3 , and propylene bromide, CH 3 .CH(Br).CH 2 Br, gives isopropyl bromide, CH 3 .CHBr.CH 3 . The compound, CH 3 .CH(C1).CH 2 I, treated with the theoretical quantity of hydriodic acid, is converted into isopropyl chloride, CH 3 .CH.(C1).CH 3 ; with an excess, there is formed isopropyl iodide, CH 3 .CH(I).CH 3 . (2) Substitution of the Nitrile Radical (CN). (See page 62.) <3) Substitution of the Nitro Group (N0 2 ). (See page 65.) By the use of diazo compounds, see the substitution of -N:NRby H. (4) Substitution of the Nitroso Group (NO). This is brought .about by boiling nitroso-compounds with concentrated hydro- chloric acids. Thus, nitroso-dimethylaniline, (CH 3 ) 2 N.NO, is converted into a salt of dimethylaniline. The same result is obtained by using a solution of alcoholic potash, or certain other reducing agents (see page 63). (5) Substitution of the Amido Group (NH 2 ). This reaction is rarely produced directly. Ethylamine at 275 C., with hydriodic ,acid, is decomposed according to the equation : C 2 H 5 .NH 2 + SHI = C 2 H 6 + NHJ + 1 2 . Tor the use of the azo derivatives in effecting this reaction, see the substitution of N :NR by H., (6) Substitution of the Diazo Group ( - N : NR) . This :reaction often takes place. Into an acid solution of the sulphate or nitrate of an amine a slow current of N 2 3 is passed (it is best to use theoretical quantities) . The salt of the diazo derivative which is formed (diazo-benzene-sulphate, 6 H 5 .N :N.O.S0 2 .OH, for example) is isolated by alcohol and ether, and then decomposed by boiling with absolute alcohol, ^according to the equation: 6 H 5 .N :N.O.S0 2 .OH+CH 3 .CH 2 .OH REDUCTION. 59^ The separation of the diazo-salt may be dispensed with; the amido compound is dissolved in a mixture of concentrated- sulphuric acid and alcohol; there is then added the theoretical quantity of a concentrated aqueous solution of sodium nitrite or an excess of ethyl or amyl nitrite. The diazo-chlorides are decomposed in the same manner by means of stannous chloride. If an excess of stannous chloride is added to a cold dilute solution of the diazo-chloride (1 mol. NaN0 2 , 1 mol. amine, 2 mols. HC1), the following^ reaction will take place : C n H tf N : N.C1 + SnCl 2 + H 2 = C n H y+ 1 + SnOCl 2 + HCI + N" 2 . In this reaction there are probably formed some hydrazines as secondary compounds. Hydrazines may also be used to replace N:N.R by H, for, by boiling them with copper sul- phate, they are decomposed with evolution of N 2 . Thus, phenylhydrazine, C 6 H 5 .NH.NH 2 , gives benzene, C 6 H 6 . In cer- tain cases, boiling the diazo body with alcohol causes the N:N.R to be replaced, instead of by H, by O.C 2 H 5 . For instance, while the ortho-diazo-benzoic acid sulphate, p TT /(I) CO.OH U4 \(2)N:N.HS0 4 > gives only benzoic acid by this reaction, the para and meta isomers yield, besides benzoic acid, meta- and para-ethoxy- benzoic acids : p H /CO.OH UM4 \OC 2 H 5 ' In place of the diazo-salts, the diazo-amido compounds (action of N 2 3 on an alcoholic solution of an amido derivative) may be decomposed by alcohol. Thus: C 6 H 5 .N: N.NH.C 6 H 5 +CH 3 .CH 2 .OH = C 6 H 6 + C 6 H 5 .NH 2 + N 2 + CH 3 .CH C 6 H 3 ^(2)NH 2 \(4) N(CH 3 ) 2 \(4) N(CH 3 ) 2 By the reduction of this body, a mercaptan is formed. (8) Substitution of Oxygen. This has already been studied in the reduction of aldehydes, ketones, nitroso derivatives, and oxyazo bodies. The reduction of the latter is identical with that of the azo derivatives. (9) Substitution of Sulphur. This takes place by the action of zinc (or of zinc dust) and hydrochloric acid, or with sodium amalgam. C 6 H 5 .CS.NH 2 is converted into C 6 H 5 .CH2.NH2. (10) The Removal of Oxygen. This takes place very rarely; in general it is the replacing of OH by H. As an example of the removal of oxygen may be cited the conversion of the sulphinic acids, R.S0 2 H, into mercaptans, R.SH, by zinc dust and dilute sulphuric acid, or with tin and hydrochloric acid. The conver- C 6 H 5 .N X C 6 H 5 .N sion of azoxy-benzene, | >0, into azo-benzene, || , C 6 H 5 .N/ C 6 H 5 .N is not complete. IV. FIXATION OF HYDROGEN. There is a fixation of hydrogen during the reduction of unsaturated compounds, or, in general, in those bodies which have several elements united by more than one bond. We REDUCTION. 6 1 have considered the reduction of aldehydes, not as one of addi- tion of H, but as the replacement of OH by H in the dihydrates : + H 2 = H 2 + CH3.CH 2 .OH. Hydrocarbons, like ethylene and acetylene, give ethane when heated to 500 C. with hydrogen; at the ordinary temperature, they combine with hydrogen in the presence of platinum black. At 150 C. in sealed tubes, the phenyl derivatives of the unsatu- rated hydrocarbons fix hydrogen by means of concentrated hydriodic acid. Thus: eHs CH2.C6H5 Tolane. Diphenyl -ethylene. Dibenzyl. Hydriodic acid permits of the addition of hydrogen to ben- zene and its numerous derivatives, and there may thus be ob- tained, by a prolonged reduction, the derivatives of benzene hexa- hydride. It is more convenient to employ absolute ethyl or &myl alcohol and sodium. In this way may be prepared piper- idine, C 5 HiiN = C5H 5 N.H 6 , from pyridine. Hydrogen cannot be added to the unsaturated alcohols with hydriodic acid, because the iodides are formed; in this case the reducing agent should be sodium amalgam, or zinc with an acid : CH 2 : CH.CH 2 OH + H 2 = CH 3 .CH 2 .CH 2 .OH Allyl alcohol. Propyl alcohol. Iron and acetic acid appear to be the best for converting unsaturated aldehydes into the saturated. Under these condi- tions, the CHO group is often changed into CH 2 OH, and some- times more readily than C = C into CH OH. Sodium amalgam in alkaline solution is the best for converting the unsaturated acids, like cinnamic acid, CeHsCH :CH.COOH, into saturated acids, like C 6 H 5 .CH 2 .CH 2 .COOH. Those which resist this action, like crotonic acid, CH 3 .CH:CH.COOH, are reduced with hydriodic acid and red phosphorus at 160 C. At 130 C. there 62 ORGANIC SYNTHESES. is a fixation of hydriodic acid; the iodo-derivative then reacts with hydriodic acid again with the splitting off of 2 atoms of iodine. Reduction causes nitriles to pass into amines: R.CN+2H 2 =R.CH 2 .NH 2 , with partial hydrolysis however; besides primary amines, there are also formed secondary and tertiary amines. 1 This reduction is generally effected with zinc and dilute sulphuric or hydrochloric acid in aqueous, alcoholic, or ethereal solution. Sodium in absolute alcohol may also be used. In this case the aromatic nitriles give secondary products, as the reduction takes place partly according to the equation : R.CN + H 2 =RH+CNH, with the formation of a hydrocarbon and hydrocyanic acid r and as the amines and hydrocarbons formed also submit to a further fixation of hydrogen. The pyrazols, with sodium in absolute alcohol, give pyrazo- lines and diamines: | C CH 2 .CH 2X CH 2 -CH 2 .NH.C 6 H 5 N.C 6 H 5 ->| >N.CeH 5 -H H=N CH = N / CH 2 .NH 2 Phenyl-pyrazol. Phenyl-pyrazoline. Phenyl-trimethylene-diamine. The oximes are reduced in the same manner to amines, and the group >C = N.OH becomes >CH.NH 2 . In this manner it is possible to realise the synthesis of aspartic acid by the reduction of the oxime obtained by the action of hydroxylamine on oxalo-acetic ester. 2 The azo compounds, 3 C 6 H 5 .N = N.C6H 5 , are readily con- 1 See Gaz. chim. Ital., vol. 9, p. 555. Ubid., vol. 17, p. 519. 3 Acid reducing agents, like stannous chloride in the presence of sulphuric, acid, convert the azo bodies into diamines. REDUCTION. 63; verted into hydrazo bodies, C 6 H 5 .NH NH.C 6 H 5 , by sodium amalgam in alcoholic solution, zinc powder, or ammonium sulphide. To use the latter, the compound is dissolved in alcohol, saturated with ammonia, then treated with a current of hydrogen sulphide. The sulphur is separated by filtration; and on the addition of water, the hydrazo body is precipitated. The azo bodies may also be reduced with ferrous sulphate in alkaline solution. It is sufficient to add the ferrous sulphate to an alkaline solution of the compound until the precipitation of ferric hydrate ceases. Acid reducing agents, such as stannous chloride in the presence of sulphuric acid, convert azo bodies into diamines. The diazo compounds are converted into- hydrazines by reducing agents like SnCl 2 in HC1 : C 6 H 6 .N : N.C1 + 2H 2 = C 6 H 5 .NH.NH 2 Diazo-benzene chloride. Phenyl-hydrazine. The hydrazines are decomposed by the fixation of hydrogen. 1 V. REDUCTION OF NITRO AND NITRO COMPOUNDS. Nitroso derivatives are converted into amines when the oxygen of the NO group is replaced by H 2 . This reduction is generally brought about by zinc and acetic acid, or with tin and hydrochloric acid. The reduction of nitrosamines furnishes a method for the preparation of secondary hydrazines : CH a \* T ^\N.NH 2 Nitroso-dimethyl- Methyl-phenyl- phenyl-amine. hydrazine. In certain cases the reaction may proceed in another manner; thus, with the preceding body, it may be : 1 The hydrazines are bodies derived theoretically from diamidogene, by substitution of paraffin or aromatic radicals (or alcoholic, phenolic, or acidio radicals) , for one or several atoms of hydrogen. There are primary, secondary,, tertiary, and quaternary hydrazines. ^4 ORGANIC SYNTHESES. The reduction of nitroso-anilides proceeds exclusively in this manner, with the evolution of ammonia and the formation of anilides : When isonitroso bodies are reduced, there is a complication of the molecule. For the reduction of oximes, see p. 62. It is well known that reduction converts N0 2 into NH 2 ; the process of Zinin for obtaining aromatic-amido compounds depends on this reaction. In the paraffin series the reduction of N0 2 (nitro-e thane, for example) to NH 2 is probably not at all analogous to that which takes place in the aromatic series. 1 The agents mostly employed for the reduction of nitro com- pounds are tin and hydrochloric acid, and a solution of stannous chloride in hydrochloric acid. The advantage of these bodies is the ease of separating the tin by sulphuretted hydrogen; in the solution there remains only the chloride of the amido com- pounds. The amines with a basic character are precipitated from their acid solutions with ammonia; amido-phenols, by sodium carbonate; amido-carboxylic acids, by sodium acetate. The reduction sometimes proceeds in an abnormal manner; //I \ pTT thus ortho-nitro-toluene, C 6 H 4 <^ \2 -^^ , with tin and hydro- XI) CH 3 chloric acid, gives para-chlor-ortho-toluidine, C6H 3 ^ (2) NH 2 ; \4)C1 ' -brom-/?-nitro- naphthalene, CioH 6 <^-^Q , with the same reduc- ing agent gives /?-naphthylamine, CioH 7 .NH 2 . In such cases, the tin is replaced by iron or zinc dust and acetic acid; there will then be obtained brom-naphthylamine, Cio the normal derivative of brom-nitronaphthalene, Ci 1 Bull. Soc. Chim., vol. 46, p. 266. REDUCTION. 65 By a very energetic reduction N02 may be replaced by H; thus, by using a large excess of iron and acetic acid, nitro- benzene, C 6 H 5 .N0 2 , gives benzene, C 6 H 6 , and ammonia; and trinitro-mesitylene, Ce^(NO$ J, S ives a cumidine, When the compound contains several N0 2 groups, it is easily possible to reduce one after another by means of sulphu- retted hydrogen, and in the order that is desired. For example : /(I) CH 3 dinitro-toluene, CoH^-(2) N0 2 , with sulphuretted hydrogen \4) N0 2 In alkaline solution, cold, gives only ortho-nitro-para-toluidine, XI) CH 3 CeH 3 ^ (2) N0 2 ; if heat is employed, its isomer is obtained, \(4) NH 2 /(I) CH 3 6 H 3 ^-(2) NH 2 ; if tin and hydrochloric acid in alcoholic solu- \4) N0 2 tion are used, the latter body only is obtained. Sometimes in reductions there occurs an evolution of C0 2 . XI) COOH Thus, dinitrobenzoic acid, C 6 H 3 ^-(2) N0 2 , gives meta- \(4) N0 2 phenylene-diamine, C 6 H 4 <^ Lc ^H^ Brom-nitrobenzoic acid, /(I) COOH / (2)Br 6 H 3 ^-(2) Br , gives meta-brom-aniline, C 6 H 4 <( >,c MT T . \(4) N0 2 Hence it is necessary to take particular precautions in the reduc- tion of nitro-carboxyl acids. The favorite method is to dissolve them in aqueous ammonia or in baryta-water, and to add ferrous sulphate in a very concentrated solution. The reduction of nitro-nitriles is surrounded with difficulties. Sulphuretted hydrogen cannot be employed, as it is liable to form a compound with the nitrile; other reducing agents cause a saponification. The best method, in certain cases, is to treat the derivative with tin and glacial acetic acid saturated with hydrochloric acid. 66 ORGANIC SYNTHESES. Nitro derivatives are sometimes reduced in a complicated manner. VI. REDUCTION WITH DECOMPOSITION OF THE MOLECULE. This reaction is to be observed in the energetic reduction of hydrazo compounds with tin and hydrochloric acid in a sealed tube. Hydrazo derivatives are reduced similarly when they are heated : /C 6 H 5 .NH\ C 6 H 5 .N C 6 H 5 .NH 2 2 I = 11 + \C 6 H 5 .NH/ C 6 H 5 .N C 6 H 5 .NH 2 . Hydrazo-benzene. Azobenzene. Aniline. The products of the condensation of aldehydes with hydra- zines are decomposed in the same manner. Ordinary aldehyde combined with phenyl-hydrazine gives a compound which, with sodium amalgam, is decomposed into aniline and ethylamine: CH 3 .CH : N.NH.C 6 H 5 + 2H 2 = C 6 H 5 .NH 2 + CH 3 .CH 2 .NH 2 . Hydrazines alone are decomposed in a similar manner. By prolonged boiling on a water bath with zinc dust and hydro- chloric acid, phenyl-hydrazine is decomposed into ammonia and aniline : C 6 H 5 .HN - NH 2 + H 2 = NH 3 + C 6 H 5 .NH 2 . Reduction with evolution of ammonia also takes place by the action of ammonia on cyan-phenine, (C 6 H 5 .CN) 3 + 2H 2 = NH 3 + C 6 H 5 .C.NH X II >.C 6 H 5 C 6 H 5 C.N ' Lophine. and by the reduction, with fixation of water (by sodium amal- gam), of the cinchomeronic acids (pyridine carboxylic acid): C 7 H 5 4 N + H 2 + H 2 = C 7 H 6 5 + NH 3 . CHAPTER III. SUBSTITUTIONS. I. LAWS OF SUBSTITUTIONS. BY the action of chlorine on hydrocarbons of a normal chain, there are usually obtained two substitution products: R.CH 2 .CH 2 .C1 and R.CH< pL , while with bromine there is almost exclusively obtained R.CH-r . Ethyl benzene behaves in the same manner on chlorination or bromination in sunlight; there is formed exclusively chlor-ethyl-benzene, C1 P , or the corresponding bromine derivative. Secondary hydrocarbons are substituted by chlorine at the carbon atom containing the least number of hydrogen atoms: (CH 3 ) 3 .CH gives (CH 3 )C.C1. Isobutane. Tertiary butyl chloride. On further action the chlorine attaches to the carbon atom which adjoins that one already linked to a halogen. In certain cases, however, this rule does not hold. 1st. With ethylidene chloride, CH 3 .CH.C1 2 , besides tri- chlor-e thane, CH 3 .CC1 3 , there is produced at the same time chlor-ethylene chloride, CH 2 C1.CHC1 2 . 2d. During the chlorination in sunlight of iso-propyl chloride, CH 3 .CHC1.CH 3 , there is formed, simultaneously with iso-propylidene chloride, CH 3 .CC1 2 .CH 3 , a certain quantity of propylene chloride, CH 3 .CHC1.CH 2 .C1. The latter is formed exclusively with iodine chloride, IC1 (at 100 C.) ; by the continued action of iodine chloride, this is finally converted 67 68 ORGANIC SYNTHESES. into trichlorhydrin of glycerol, CH 2 C1.CHC1.CH 2 .C1. This re- action is interesting, as it allows of the synthesis of glycerol. 3d. Ethyl bromide, C 2 H 5 .Br, at 200 C., with bromine gives ethylidine bromide, CH3.CHBr 2 ; but in the presence of aluminium bromide, Al 2 Br 6 , there is formed only the bromide of ethylene, CH 2 Br.CH 2 Br. Propyl and iso-propyl bromides. CH 3 .CH 2 .CH 2 Br, and CH 3 .CHBr.CH 3 , on bromination, both. yield the same propylene bromide, CH3.CHBr.CH 2 Br. Fatty acids with halogens yield principally the a-deriva~ tives. Propionic acid with bromine gives the a-brom and a-di- brom-propionic acids: CH 3 .CHBr.COOH and CH 3 .CBr 2 .COOH. The aromatic series affords the most general laws. 1 It may be said that usually the introduction into a compound of substituents of the first group, Cl, Br, I, OH, NH 2 , C n H 2n+1 , OR, NHR, NH-COR, will usually cause the second substituting group to go to the ortho and para positions, while substituents of the second group, N0 2 , S0 3 H, COOH, CHO, CO, CN, CH 3 .CO, etc., will usually form meta compounds with the second radical. Thus, chlor-benzene, C 6 H 5 C1, with nitric acid, gives a mixture of ortho- and para-chlor-nitrobenzenes : rH /(D Cl , rH /(D Cl CeH4 \(2) N0 2 and CeH4 \(4) With sulphuric acid, it gives para-chlor-benzene sulphonic acid r <^ \.l ~~ ^yry. Phenol with nitric acid gives ortho-nitro- ( ( ^ Nitro-benzene with nitric acid yields principally meta-dinitro- 1 See Armstrong, Jour. Chem. Soc., 1887. phenol, C 6 H 4 < > and Para-nitro-phenol, C 6 EL SUBSTITUTIONS. 69 benzene, CeH^/J N Q 2 , with but a small amount of the ortho and para isomers. Occasionally two different groups- have the same action on the substituant. Thus, para-nitro- /(\\ toluene, C 6 H 4 < )7\ nn> on chlorination gives C 6 H 3 -(2) Cl 4 \ 4) N0 2 C 6 H 5 .S0 2 .OBr + HBr. In acid amides, the halogen replaces the hydrogen, attached to the nitrogen, by action in alkaline solution. Thus, with acetamide, CH 3 .CO.NH 2 , there is formed acetbromamide, CH 3 .CO.NHBr; these compounds are difficult to isolate on account of their ready decomposition. The paraffin amines, with halogens, exchange a hydrogen in the NH 2 group. Thus, by passing chlorine into an aqueous or alkaline solution of ethylamine here is formed ethylamine dichloride, C 2 H 5 .NC1 2 . B. Exchange of Halogens for One Another. The action of chlorine on brom- and iodo-compounds does not cause a displacement of hydrogen, but an exchange of bro- mine or iodine for chlorine; so, in order to have chlor-brom- or chlor-iodo-compounds, it is necessary to first introduce chlorine. 1 The substitution of bromine by chlorine is effected by the aid of the pentachlorides of antimony and phosphorus. Thus: 2C 2 H 5 Br + SbCl 5 - 2C 2 H 5 C1 + Br 2 + SbCl 3 . Ethylene bromide, according to the quantity of pentachloride tion in benzene is decomposed by caustic potash, giving C H 2 Br 3 .OH. With potassium iodide it reacts according to the following equation: C 6 H 2 Br 3 .OBr+ 2KI= C 6 H 2 Br 3 .OK+ 1 2 . 1 This reaction, however, may be used for obtaining chlorine substitution products: instead of allowing chlorine to act "directly on the body, the liquid iodine derivatives are used, kept under water, and heated with chlorine water until liberation of iodine has ceased. In the aromatic series, only iodo- aniline, C a H 4 ! 2 undergoes this reaction. SUBSTITUTIONS. 75 of antimony used, is converted into ethylene chlor-bromide, CH 2 .C1 CH 2 .C1 I or ethylene chloride, | ; while with methyl or ethyl- CH 2 Br CH 2 .C1 dibromides, CH 2 Br 2 and CH 3 .CH.Br 2 , the two bromine atoms are replaced at once. Bromine can also be replaced by heat- ing the compound gently with mercuric chloride, HgCl 2 : 2CH 3 .CHBr .CH 2 Br + HgCl 2 - 2CH 3 .CHCl.CH 2 Br + HgBr 2 . Iodine is still more readily replaced by chlorine, not only by the direct action of the latter, but also by the double decom- position of an iodine compound with certain metallic chlorides, like mercuric chloride, HgCl 2 , the mixture being heated in the presence of water or ether. lodoform, under these con- ditions, only has two iodine atoms replaced, giving CHIC1 2 . The substitution of chlorine by bromine takes place by the direct action of bromine only in the case of acid chlorides (which then behave like chloric acid, in which the chlorine is replaced by bromine), and in some other cases by double decomposition. Thus, chlor-acetic acid, CH 2 C1.COOH, heated to 150 C. in a sealed tube with hydrobromic acid or potassium bromide, is converted into brom-acetic acid, CH 2 .Br.COOJL The acid chlorides, on the contrary, under these conditions do not react: for instance, acetyl chloride, CH 3 .CO.C1, heated for several hours at 100 C. with potassium bromide, is not changed. Aluminium bromide readily attacks alkyl chlorides; by its action, carbon tetrachloride, CCL*, is converted into the tetrabromide, CBr 4 . 1 Iodine replaces chlorine when compounds of the latter (except in the aromatic series) are treated with hydriodic acid or metallic iodides CeHs.Cl when heated with H for fifteen hours at 235 C., gives C 6 H 6 + HC1 + I.) The reaction takes place in the cold without an excess of acid. For unsaturated 1 For the preparation of the halides of aluminium and their application to halogen substitution products, see Gustavsonn, Action of the Halogen Salts of Aluminium on Organic Compounds, Moscow, 1883 (in Russian). 76 ORGANIC SYNTHESES. compounds, or those containing OH (which can fix HI or exchange OH), potassium iodide may be used, under 100 C. in alcoholic solution. Calcium iodide, Cal2, may also be used (see replacement of bromine by iodine). The best method of converting the higher chlorine deriva- tives into iodine compounds is to use aluminium iodide dis- solved in carbon disulphide. Ethylidine chloride, CH 3 .CHCl2, becomes ethylidine iodide, CH 3 .CHI 2 . The trichlorhydrin of glycerol with aluminium iodide gives allyl iodide, CH 2 = CH.CH 2 I, together with aluminium chloride and iodine. Iodine is replaced by bromine by the direct action of the latter, or by boiling with bromine water, or by double decom- position in a sealed tube with metallic bromides, such as those of mercury, copper, or silver. For example: 2CH 3 .CHLCH 3 + HgBr 2 = 2CH 3 .CHBr.CH 3 + HgI 2 . In the higher substitution products, iodine may be replaced in part or completely. Thus: 2CHI 3 + Br 2 = 2CHI 2 Br + 1 2 . Sometimes, by the action of the hydriodic acid, there is formed an unsaturated compound which combines with the bromine. For this reason, by the action of bromine on sec- ondary butyl iodide, CH 3 .CH 2 .CHI.CH 3 , there is formed CH 3 .CHBr.CHBr.CH 3 . Iodine occurring in the aromatic nucleus, in general, is not replaceable by bromine; but the latter acting on iodo-aniline gives tribrom-aniline : NH n TT / Br 3 > ^6ki.2< Bromine and chlorine are replaced by iodine by double decomposition with the iodides of potassium or calcium. The bromine compounds are heated with calcium iodide (dried with exclusion of air) in sealed tubes, generally below 100 C. SUBSTITUTIONS. 77 In this manner, propyl bromide, CHa.CHBr.CHs, is converted into the iodide, CH 3 .CHI.CH 3 . On account of the insta- bility of di-iodo compounds in which the iodine occurs attached to adjoining carbon atoms, these bodies, at the moment of their formation, are decomposed into unsaturated derivatives and iodine is set free. The substitution of chlorine and iodine by fluorine takes place by double decomposition of chlorine compounds with arsenic fluoride, or, in the case of iodine compounds, with silver fluoride, C 2 H 5 I+AgF = C 2 H 5 F+AgI. C. The Substitution of Other Groups by Halogens. The replacement of NH 2 by a halogen is accomplished through the diazo compounds by the conversion of the NH 2 into N :N.R, and subsequently replacing this group with a halogen. 1 The halogen derivatives of the diazo bodies, such as diazo-benzene chloride, C 6 H 5 .N:N.C1, are directly decomposed on heating, giving, in the case quoted, chlor-benzene, C 6 H 5 C1 and N 2 . The halogen substitution products of benzene and its deriva- tives are also obtained by heating a diazo salt (sulphate or nitrate) with concentrated halogen acids (instead of the aqueous solution of hydrochloric acid, its acetic acid solution may be used) : The best means of preparing the chlorine substitution deriv- atives is to prepare the chlor-platinate of the diazo body; the precipitate is difficultly soluble in alcohol, and is collected, dried, and heated with ten times its weight of a mixture of dry soda and ground glass: 1 The diazo derivatives of the aliphatic series, treated with halogens or halogen acids, have the N=N group directly replaced by a molecule of halogen or halogen acid. 7$ ORGANIC SYNTHESES. The chlor-platinates may be replaced by the double salts of the diazo-chlorides with the cuprous salts of chlorine or bromine, Cu 2 Cl 2 and Cu 2 Br 2 . To the cold solution of the amine in dilute hydrochloric acid, there is added, little by little, the theoretical quantity of sodium nitrite, and then a solution of hydrochloric acid heated with cuprous chloride is gradually added. The double compound which is formed is generally decomposed with dis- engagement of nitrogen, producing the chloride and cuprous chloride, which readily separates out, owing to its insolubility. Halogen substitution products can also be obtained by the action of halogen acids on diazo-amido compounds. This is the best means of preparing iodine and fluorine compounds. Thus, benzene fluoride, C 6 H 5 F, is prepared by the action of hydrofluoric acid on C6H 5 N:N.NC 5 Hio. The latter body is produced by the action of diazobenzene chloride on piperi- dine. For preparing bromine compounds there may be utilized the decomposition of the perbromides, which are formed by the action of bromine in hydrobromic acid solution on an aqueous solution of the diazo sulphate. The compound is washed with alcohol and dried. On heating, alone or with glacial acetic acid, it is decomposed according to the equation: C 6 H 5 N : N.Br .Br 2 = C 6 H 5 Br + N 2 + Br 2 . The substitution of the -N = N- group by halogens or halogen acids takes place by the action of these on the diazo compounds of the aliphatic series. Thus, diazo-acetic-ester gives di-iodo-acetic-ester with iodine in alcoholic solution and at the ordinary temperature; 1 by the action of hydrochloric acid it gives chlor-acetic ester. CHN 2 .CO.OR+I 2 =CHI 2 .CO.OR+N 2 , CHN 2 .CO.OR + HC1 = CHaCl.CO.OR + N 2 . 1 Titration with iodine is used in the quantitative determination of the diazo compounds of the aliphatic series. SUBSTITUTIONS. 79 Substitution of OH by a halogen. The alcoholic OH group is replaced by halogens on treatment with a concen- trated halogen acid, or with a mixture which liberates such acids (NaCl and H 2 S0 4 ; KBr and H 2 S0 4 ). With hydrochloric acid the action is quite slow, arid heat is generally required to bring about the reaction, either in a sealed tube or in the presence of dehydrating agents. Hydro- bromic acid reacts more easily, and hydriodic acid still more so, and in the latter case it is not always necessary to use heat, Instead of acids, bromine or iodine may also be allowed to act on the alcohols in the presence of phosphorus. It must not be forgotten that an excess of acid may act as a reducing agent. 1 In certain cases this reaction takes place more easily than that of replacing OH by I. Thus, iod-acetic acid, CH 2 I.CO.OH, reacts in the cold, even with sufficiently diluted hydriodic acid; while glycollic acid, CH2(OH).CO.OH, only reacts when heated with concen- trated acid. This is why iod-acetic acid is not formed by the action of hydriodic acid on glycollic acid. Lactic acid behaves in the same manner, which distinguishes it from the iosmeric /pTT r\Ti hydracrylic acid, CH 2 \ 2 , which readily forms an iodide, Compounds rich in hydroxyl, with hydriodic acid, readily exchange one or more of their OH groups for H, by reason of the reaction of the acid with the iodo product: thus, with glyceric acid is obtained /9-iodo-propionic acid, CH 2 LCH 2 .CO.OH; the iodine which occurs in the primary group is always the more stable. In polyatomic alcohols, on the contrary, the iodine which is found in the secondary group (called beta) shows the greater stability. If in the compound there are several hydroxyl groups, according to the conditions of the experiment, it is possible to replace all or some of them with chlorine. For an incomplete exchange, there may be used, among others, sulphur chloride, S 2 C1 2 , which reacts, 2 for exam- 1 See substitution of iodine by hydrogen. 2 The product obtained always contains sulphur. So ORGANIC SYNTHESES. pie, with glycol, according to the equation: CH 2 .OH CH 2 C1 2 1 +23 2 C1 2 = 2| + HC1+S0 2 CH 2 .OH CH 2 .OH Instead of using the halogen acids, the different halogen compounds of phosphorus may be used, which react with great energy. In certain bodies, as, for example, phenols, carboxylic, and sulphonic acids, it is only by this means that OH may be exchanged for a halogen. 1 The trichloride of phosphorus is used in cases where other reactions than the exchange of OH may take place, such as the fixation of hydrochloric acid. Propargyl alcohol reacts according to the following equation: Sometimes the action of the trichloride leads to the for- mation of anhydrides, as with benzhydrol : (C 6 H 5 ) 2 CH.OH, gives [(C 6 H 5 ) 2 CH] 2 0. The pentachloride is usually applied in cases where the body contains several hydroxyl groups and it is necessary to replace them all; erythrite, for example, gives erythrene tetra- chloride, C^eOU. The pentachloride and pentabromide of phosphorus are used for the replacing of OH by Cl and Br in phenols and in carboxylic and sulphonic acids. In aliphatic acids, the same result is gained by the action of PClsor POCls. 2 1 The OH of carboxylic acids may be replaced by chlorine with hydrochloric acid only in the presence of phosphoric anhydride. Thus, by passing a current of the gas into glacial acetic acid mixed with P 2 O 5 , acetyl chloride is formed .even at C. But benzoyl cloride can only be obtained by passing hydrochloric acid gas into a mixture of benzoic acid and P 2 O 5 heated to 200 C. 2 For the preparation of the acid bromides, in place of PBr 3 , it is more con- venient to use a mixture of the acid with phosphorus, while bromine is added from time to time in quantity corresponding to the equation: 3RCO.OH+2PBr 3 =3R.COBr+3HBr+P 2 O 3 . SUBSTITUTIONS. 81 By the action of PC1 5 on the oxy-acids, the hydroxyl groups are replaced by Cl. The aromatic oxy-acids at first give com- binations which contain phosphorus and chlorine like PC\s, which finally become, by the action of the pentachloride or simply by the action of heat, chlorinated /COC1 acid chlorides, CeH^ Glycollic acid gives chlor-acetyl- chloride, according to the following equation: CH.OH CH 2 .C1 | +2PC1 5 = | +2POC1 3 + 2HC1. CO.OH CO.C1 The same reaction takes place with the perbromide. In order to obtain a brom derivative of an oxy-acid, it is necessary to heat the latter with hydrobromic acid, or to use the perbromide with the ether of the oxy-acid. Thus: CH 2 .OH CH 2 .Br H-PBrsH +POBr 3 + HBr. CO.OC 2 H 5 CO.OC 2 H 5 With certain polybasic oxy-acids there are formed unsatu- rated derivatives of the acids: thus, malic acid gives fumaryl chloride* tartaric acid is converted into chlor-malyl chloride; CO.OH CO.C1 CH.OH CH | +3PC1 5 = || +3POC1 3 +4HC1. CH 2 CH I I CO.OH CO.C1 Replacing a halogen by OH. (See Chapter on Oxidation.) The replacing of in the CO group of aldehydes, ketones, ketonic acids, and other compounds by Cl or Br is done by 82 ORGANIC SYNTHESES. using the perchloride or perbromide (it is better to take the chlor-bromide, because it is easier to separate the oxychloride by oxidation). The reaction takes place in the cold; often it is necessary to moderate the temperature by cooling, or by addition of oxychloride; in certain cases it is necessary to heat either under ordinary pressure or in sealed tubes. During this reaction the halogen acid is some tunes disengaged. The replacing of by I 2 cannot be done directly. It is necessary to operate indirectly by first splitting off water, then treating with hydriodic acid, which is then fixed by the unsaturated body : CH 3 .CO.CH 3 - H 2 = CH 3 .C = CH, D. Preparation of the Derivatives of Nitrous and Nitric Acid? and of Hydroxylamine. Replacing H by NO. The introduction of the NO group by the substitution of hydrogen linked to a carbon atom only takes place in a few cases. It is believed that this reaction occurs when mixture of potassium nitrite and sulphuric acid is allowed to act on an alkaline solution of secondary nitro compounds, such as nitro-isopropane, (CH 3 ) 2 CH.N0 2 , which is converted into isopropyl-pseudonitrol, (CH 3 ) 2 C(NO)N0 2 . 1 1 Nitro compounds are differently affected by nitrous acid, according to- whether they are primary, R.CH 2 .NO 2 , secondary, K 2 :CH.NO 2 , or tertiary, R 3 j C.NO 2 . Primary nitro compounds are converted into nitrolic acids (oximid- compounds) which dissolve in alkalies with an intense red color: CH 3 .C;H 2 j.N0 2 +|OjN.OH = C Secondary nitro compounds give pseudo-nitrols, which are soluble in alkalies, giving a deep blue color: Tertiary nitro compounds do not react with nitrous acid. These reactions afford a delicate method .of detecting primary, secondary, and tertiary alcohols; the alcohols are first converted into iodides (with PI 3 ), and then treated with SUBSTITUTIONS. 83 Certain aromatic tertiary bases, such as dimethyl-aniline, 6H 5 N(CH 3 )2, are changed into nitroso derivatives by the theoretical amount of potassium nitrite or amyl nitrite added to their hydrochloric acid solutions, well cooled. This reac- tion does not appear to be general; for the ortho- and para- dimethyl-toluidines do not form nitroso derivatives, while the meta-body furnishes C 6 H3(NO)(CH3)N(CH 3 )2. It is pos- sible that this may not be a nitroso compound, but an iso- nitroso compound. The nitroso-amines of the aromatic bases are converted into para-nitroso derivatives, similar to para-nitroso-dimethyl-anil- Ine, by an alcoholic solution of hydrochloric acid. It is thought by some that nitroso-dimethyl-aniline may be an azoxy deriva- tive and may have the quinonoid formula N=/ N = N(CH 3 ) 2 , HO.N-/ N )>= I \ / I \ / which would explain the formation of the sodium salt of para nitroso-monomethyl-aniline : NaO.N=/ N >=N . \OH The other aromatic derivatives either do not react with nitrous acid, or behave in quite a different manner. Thus, with phenol, there is formed a body which for long was considered as nitroso-phenol, but which is really a quinone-oxime. Per- haps it is formed as an isomeride of the isonitroso compound silver nitrite (AgNO 2 ). The nitro compounds which are thus formed are dis- tilled off and mixed with potassium nitrite and sulphuric acid; on adding an excess of potassium hydrate the liquid becomes either red or blue, or remains unchanged, according to whether the alcohol was primary, secondary, or ter- tiary. Only the alcohols of low molecular weight show these color reactions. 84 ORGANIC SYNTHESES. which may at first be produced: -- > C6H N.OH. Nitrous acid with alcohols of the aliphatic series simply replaces the hydrogen of the alcoholic group to form nitrous esters. These are easily obtained by saturating the alcohol with N 2 3 , and the reaction, if necessary, is completed by the aid of heat; or, better, to a mixture of the alcohol with sul- phuric acid and water, there is added a solution of potassium nitrite, and the ester formed is subsequently isolated. A very convenient method for preparing these esters is to employ the double decomposition between the alcohols and the nitrous ester of glycerine. 1 The hydrogen united to the nitrogen of imido compounds is easily replaced by NO by the action of nitrous acid; ia this manner are formed the nitrosamines : These nitrosamines are prepared by passing N 2 0a into a solution of the imide base (in alcohol, ether, benzene, acids, etc.). The body produced is separated by evaporating the solution or by diluting with water. There may also be used potassium nitrite, which is added in the theoretical quantity to> a hydrochloric acid solution of the base; or the nitrous esters of ethyl and amyl alcohol may be employed. The anilides behave in the same manner, but the nitrosa bodies .formed are distinguished from the nitrosamines by their instability. Nitroso-anilide, (C 6 H 5 )(CH 3 .CO)N.NO, is prepared by passing N 2 0s into a solution of the anilide in glacial acetic acid. Piperidine and its derivatives (for example, conine or ct-propyl-piperidine) and tetrahydro-quinoline also give nitroso compounds. 1 Gaz. chim. ital.. vol. 15, p. 351. SUBSTITUTIONS. 85 Substitution of H by N0 2 . This substitution only takes: place easily in the aromatic series by the action of nitric acid. In the aliphatic series nitro compounds are rarely formed. Mention, however, may be made of the formation of C(N0 2 ) 4 , nitro-isobutylene, and nitro-barbituric acid; it may also be remarked that nitro-styrene probably has the formula C 6 H 5 .CH :CH.N0 2 . Further mention will be made of those compounds, known as dinitroso, obtained by the action of nitric acid on ketones. In the aromatic series, nitration is a very general one. In order to nitrate the aromatic hydrocarbons, they are added little by little to fuming nitric acid, and it is better that the latter does not contain any nitrogen oxides; or the acid may be added slowly to the hydrocarbon. A sufficient quantity of water is added to isolate the nitro derivative. It is often easier to regulate the nitration by operating with a glacial acetic acid solution. The nitric acid employed in the majority of cases has a density of 1.50 to 1.52. 1 In the nitration of benzene, an excess of benzene diminishes the yield of nitro- benzene, an excess of acid increases it. Nitration in general does not have to be made at elevated temperatures; it is often necessary to use refrigeration, some- times to C., for nitric acid also acts as an oxidizing agent;, and, if the hydrocarbons have side-chains, they may be con- verted into carboxylic acids or ketones. The ease of nitra- tion increases with the number of side-chains. In order to obtain higher nitro products, the reaction is carried out with a mixture of nitric and sulphuric acids, or with the aid of heat, if necessary. The sulphonic acid compounds, if heated strongly during nitration, may have their SOsH group replaced. Thus mesitylene sulphonic acid, C 6 H 2 (CH 3 )3S0 3 H, if it is not cooled,, gives dinitro-mesitylene, C 6 H(N0 2 ) 2 (CH 3 ) 3 . The nitro-sulphonic acids, being soluble in water, cannot 1 For the action of nitric acid of different concentrations on the aromatic- hydrocarbons and their derivatives, see Annalen, vol. 224, p. 283. ORGANIC SYNTHESES be separated by addition of the latter; in order to accomplish this, the acid liquor is diluted with a little water and the excess of nitric acid is evaporated off on a water-bath. Phenols are nitrated so easily that it is not necessary to use fuming nitric acid. Phenolic ethers behave in the same manner. The amido compounds l react readily with nitric acid, and give at once higher nitro products, or even resinous matters ; also it is only necessary to use the theoretical quantity of acid or to employ it dilute. With aniline, for example, the amine is dissolved in a large quantity of cold sulphuric acid, and there is added, little by little, a mixture of the theo- retical quantity of nitric acid with sulphuric acid. When the reaction is finished, the mass is diluted with water, and the excess of acid neutralized in order to precipitate the nitro- amido compound. In the majority of cases the amido com- pound itself is not nitrated, but the anilide; the reaction pro- ceeds nicely, and, according to the concentration of the acid, either mono- or dinitro products can be obtained. The N0 2 group always replaces the hydrogen in the benzene nucleus of the base, even in the case where the anilide contains the residue of an aromatic acid. The anilides of the oxy-benzoic acids offer an exception; in the nitration of salicyl anilide, n TT /(I) CO.NH.C 6 H 5 ., . . , u . . , . C 6 n 4 N.OH. When nitrous acid acts on bodies which contain a CH 2 group (adj oining negative groups such as CO or N0 2 ), the following reaction takes place: R 2 .CH 2 + NO.OH = H 2 + R 2 .C : N.OH ; and isonitro compounds are formed, thus: CO.O.C 2 H 5 CO.OC 2 H 5 H 2 +NO.OH = H 2 0+C = N.OH $ CO.O.C 2 H 5 CO.OC 2 H 5 CO.CH 3 CO.CH 3 CH 2 +NO.OH = H 2 0+C=N.OH CO.OC 2 H 5 CO.OC 2 H 5 In order to obtain isonitroso-malonic ester, N 2 0a is passed into a mixture of malonic ester and sodium alcoholate until no further absorption takes place; the isonitroso compound is separated by the addition of water. In order to obtain iso- nitroso-aceto-acetic ester, potassium nitrite is added to a solu- tion of aceto-acetic ester in an alkaline alcoholic mixture, while it is well cooled, and then 20 per cent, sulphuric acid is run in. After the reaction is completed the liquid is made alkaline, and any unchanged aceto-acetic ester is removed by ether; on acidifying again, the isonitroso compound is separated. SUBSTITUTIONS. 91 Benzyl cyanide, C 6 H 5 .CH 2 .CN, with amyl nitrite in the pres- ence of alcohol, is also converted into an isonitroso compound, The substituted aceto-acetic esters of the general formula CH 3 .CO.CHR.CO.OC 2 H 5 , during their transformation into isonitroso compounds, are saponified at the same time, and the final reaction may be, expressed thus: /riTT Ha-COXK^pJL +|H|+|0|N.OH |CQ.O|C 2 H 5 OH| CH 3 I = CH 3 CO .C : N.OH + C0 2 + C 2 H 5 .OH ' The isonitroso ketones may be obtained by treating ketones with amyl nitrite in the presence of hydrochloric acid or sodium ethylate. Primary nitro compounds (or rather their metallic salts) are converted into nitrolic acid derivatives (the salts) by nitrous acid. It is supposed that H 2 is exchanged for >N.OH. R.CH 2 .N0 2 --> R Nitrolic acid. During the formation of diazo compounds, there also occurs the substitution of H 2 (of the amido group) by >N.OH (or >NC1, >N.N0 3 , etc.). Substitution of a halogen by N.OH takes place in the action of hydroxylamine on compounds which contain two atoms of halogen attached to a single carbon atom. Dibrom- nitro-e thane, CH 3 .CBr 2 .N0 2 , is presumably converted into ethyl nitrolic acid, p/N.OH f . ' C \N0 2 (?) 9 2 ORGANIC SYNTHESES. The halogen substitution products of ketones behave in the same manner; but their oxygen also reacts with hydroxyl- amine and produces oximido ketoximes; CO +2H 2 N.OH=C:N.OH +H 2 0+2HC1. CH.C1 2 CHrN.OH Substitution of by N.OH. Aldehydes and ketones, as well as quinones, replace the by N.OH by the action of hydroxyl- amine in aqueous or alcoholic solution, giving rise to aldoximes, ketoximes, and quinone-oximes. The reaction proceeds tran- quilly in the cold by leaving the two bodies in contact. It is more convenient to use a solution of hydroxylamine hydro- chloride (the presence of ammonium chloride is not injurious) iwdth the theoretical quantity of sodium carbonate. Ketonic or aldehydic acids and their esters readily react with hydroxylamine. Bodies which contain two CHO or CO groups react with two and sometimes with only one molecule of hydroxylamine. Glyoxal gives glyoxime: CHO CH:N.OH +2H 2 N.OH=| + 2H 2 0. HO CH:N.OH X-', A N.OH The oxime obtained with anthraquinone, CeEU /U CO / CeH4r does not react any further with hydroxylamine, while its isomer, prepared with phenanthraquinone, reacts at 180 C. with another molecule of hydroxylamine, giving the dioxime or its anhydride : C 6 H4.C:N.OH C 6 H 4 .C:N.OH > | | O C 6 H 4 .C:N.OH SUBSTITUTIONS. 93 The oxime, which corresponds to benzoquinone, and which is para-nitroso-phenol, obtained by the action of hydroxyl- -amine on quinone, reacts with another molecule, giving quinone- dioxime, C 6 H 4 (N.OH) 2 . E. Preparation of Ammonia Derivatives. Substitution of a halogen by NH 2 . In the aliphatic series, and in the side-chains of the aromatic series, this takes place through the action of ammonia on the halogen esters. How- ever, the reaction cannot be expressed by the simple equation RI + 2NH 3 = RNH 2 +NH 3 .HI, because, besides the primary amines, there are also produced secondary amines, according to the time, the temperature, and the mass of the reacting bodies. 1 It is also necessary to take into consideration whether aqueous or alcoholic solutions of ammonia are used, and also the character of the halogen compounds. In the case of primary compounds, there are formed not only tertiary amines but also ammonium derivatives; in the case of secondary bodies, the chief product consists of primary bases. The tertiary iodides react with ammonia but do not give amines; they are decomposed with the formation of unsaturated hydro- carbons. 2 The reaction is carried out in sealed tubes at 100 C. 3 The separation of the primary amines from the products formed with them is sometimes very difficult. With the lower homologues, recourse cannot be had to distillation, as the difference between the boiling-points of the primary, secondary, and tertiary amines is too small. Generally, recourse is had to the oxalic esters. The product of the reaction 1 According to some, these bodies are formed successively; and, as there is always an excess of ammonia, the free bases are produced, their alkalinity being more feeble than that of ammonia, which decomposes their salts. 2 Also, during the reaction of secondary iodides with ammonia and the amines, the unsaturated hydrocarbons are readily formed. Isopropyl iodide, (CH 3 ) 2 CHI, with isopropylamine, (CH 3 ) 2 CH.NH 2 , gives propylene, CH 3 .CH :CH 2 .) 3 Methylamine can be formed at the ordinary temperature by liquefying a mixture of methyl chloride and ammonia. 94 ORGANIC SYNTHESES. is evaporated on a water-bath, then potash is added to the mixture of the salts, and on distillation the ammonium com- pound, is left behind, as it is not decomposed by potash. The distillate consists of the amines R.NH 2 , R 2 .NH, and R 3 .N, This mixture of amines is then treated by the oxalic ester method. The aromatic amines may be separated by the fractional crystallization of their salts; the salts of the secondary amines are less soluble than those of the primary, and more so than those of the tertiary. Also the difference in basicity is utilized, and the separation may be accomplished by means of acids. Thus, a mixture of benzylamines, taken up with a small quan- tity of dilute hydrochloric acid, will give up at first the mono- and di-benzylamines, (C 6 H 5 .CH 2 ) .NH 2 and (C 6 H 5 .CH 2 ) 2 .NH r and these may be separated subsequently by crystallization; the residue will be the tertiary amine, (C 6 H 5 .CH 2 ) 3 .N. The halogen of chlorhydrins, (CH 2 .C1.CH 2 OH), as well as the substitution products of the carboxylic acids, may also be replaced by NH 2 . The ester of chlor-formic acid, C1CO.OR, with ammonia, gives carbamic acid, NH 2 CO.OR. The esters of other chlor-acids behave in a slightly different manner; they are converted into chlor-acid amides. With chlor-ethyl CH 2 C1 CH 2 C1 acetate, , there is formed chlor-acetamide, | > CO.OC 2 H 5 CO.NH 2 which, heated with ammonia, has the chlorine replaced to give amido-acetamide, NH 2 CH 2 .CO.NH 2 . For the preparation of similar amines, heating with lead hydrate is employed; the lead salt thus obtained is decomposed by means of hydrogen sulphide. The other esters of the inorganic acids behave in the same manner as the halogen compounds. In the aromatic nucleus the halogen is seldom replaced by the amido group by treatment with ammonia. Brom-nitro- benzene, CeH^ L) Br *' and similarl y chlor-nitrobenzene, SUBSTITUTIONS. 95 , heated in sealed tubes at 180 C. with am- monia, give ni tramline; but the meta-brom-nitrobenzene scarcely reacts at all with ammonia. In chlor-dinitrobenzene, /(I) Cl C 6 H 3 ( (2) N0 2 , the chlorine is replaced by simply boiling \(4) N0 2 with ammonia water. The corresponding bromine compound reacts with difficulty, and the iodine compound is even less reactive. If two N0 2 groups are found in the ortho posi- tion to one another, one of the two can be replaced by NH 2 . /(I) Cl Thus chlor-dinitrobenzene, C 6 H 3 ^-(3) N0 2 , is converted into \(4) N0 2 /(I) Cl chlor-nitrotoluidine, C 6 H 3 ^(3) NH 2 . \(4) N0 2 The substitution of halogens by NH 2 takes place easily by the action of aqueous or gaseous ammonia on the chlorides of the carboxylic acids. The reaction takes place in the cold and gives very good yields. In the aliphatic series there is also formed a secondary amine as a by-product. In carrying out the reaction, the acid and phosphorus trichloride are taken, and not the ready-prepared chloride. By cautiously treating with ammonia such compounds as dichlor-propionyl chloride, CH 3 .CC1 2 .CO.C1, the chlorine is only replaced in the COC1 group. The chlorides of the sul phonic acids react with difficulty; their amides can be prepared, nevertheless, by using gaseous ammonia dissolved in ether, and, less readily, by prolonged boiling with aqueous ammonia. Substitution of OH by NH 2 . This can only be effected by heating with ammonia or its salts in sealed tubes, with or without dehydrating agents. With the aliphatic alcohols there are formed primary, secondary, and tertiary amines, and often, as by-products, unsaturated hydrocarbons. One may conveniently use the ammoniacal chloride of zinc, which $ ORGANIC SYNTHESES. is prepared by passing ammonia over powdered zinc chloride heated to 300 C. The latter absorbs four times its weight of ammonia. The body R.OH is heated for fifteen hours at 250 C. with the ammoniacal chloride. The yield is from 50 to 75 per cent, of the weight of the alcohol used in the reaction. The reaction with phenols takes place more readily. /3-naph- thylamine, with a certain quantity of /?-dinaphthylamine, is obtained by passing dry ammonia over /?-naphthol strongly lieated. Anthrol gives anthramine: /\ /x C 6 H 4 C 6 H 3 .OH -- > C 6 H 4 | C 6 H 3 .NH When heated to 200 C. with aqueous ammonia, alizarin is converted into diamido anthraquinone. Many of the nitro- phenols also react readily with ammonia in concentrated solu- tion. With other phenols, ordinary phenol for example, it is necessary to heat with ammoniacal chlorides of zinc or cal- cium at elevated temperatures. One part of the phenol remains unattacked; but it is easy to separate this from R.NH2 by the aid of acids and alkalies. The cyan-hydrins (produced by the combination of hydro- cyanic acid with aldehydes and ketones) react with ammonia with remarkable ease, and give the nitriles of the a-amidocar- boxylic acids. Thus: CH 3 \ p /OH NH CH 3 \ r /NH 2 H H/ ( \CN H ' NH3= H/\CN The latter body, on saponification, gives amido-propionic acid or alanine. The acids of the aliphatic series have their OH replaced by NH 2 , and are converted into amides, when they are treated with ammonium sulphocyanide, CNS.NH 4 : 2CH 3 .CO.OH + CNS.NH4 = 2CH 3 .CO.NH 2 + COS + H 2 0. SUBSTITUTIONS. 97 There is generally formed a certain quantity of nitrile as a secondary product. Substitution of OH by NH.R and NR 2 . This is accom- plished by heating phenolic bodies with primary and secondary amines, NH 2 .R and NH.R 2 . The reaction is sometimes more easily brought about than with ammonia. Thus aurine is more readily converted into trimethyl-rosaniline than into Tosaniline : /C 6 H 4 .OH C^-C 6 H 4 .OH \C 6 H 4 .0 /C 6 H 4 .NH.CH 3 A} 6 H 4 .NH.CH 3 \C 6 H 4 .NH.CH 3 .C1 Aurine. Hofmann'a violet. a- and /?-naphthols are converted into monomethyl a- and /?-naphthylamines by the action of monomethylamine. Fluorescein heated with dimethylamine gives tetra- methyl-diamido-fluorescein, or rhodamine, a magnificent red dyestuff : OH (CH 3 ) 2 N N(CH 3 ) 2 Fluorescein. Rhodamine. These cases can be considered as indirect condensations with disengagement of water. Substitution of O by NH. This is brought about in cer- tain cases by the action of ammonia. Thus, different deriv- atives of pyrone, C 5 H 4 2 , heated with ammonia, and some- times even at the ordinary temperature, are converted into pyridone derivatives, C 5 H 4 O.NH. The acid C 5 H 3 2 , CO.OH, ORGANIC SYNTHESES. forms C 5 H40.N.CO : OH. The following formulas represent pyrone and pyridone: As derivatives of pyrone, there are, among others, meconia acid, chelidonic acid, which is tribasic, and pyromeconic acid, which probably does not contain a carboxyl group, but which. should be hydroxy pyrone, C 5 H 3 (OH)02. On heating fluorescein with ammonia there is substituted not only OH by NH 2 , but also by NH. The following formulas for these bodies have been given: OH OH NH 2 NH Fluorescein. Diamido-imido-fluorescein. Substitution of S by NH. When sulphur is attached to a carbon atom with two bonds, it may be replaced by NH by the action of ammonia. This reaction generally takes place only in the presence of substances reacting with the hydrogen sulphide liberated, such as the oxides of lead or mercury. Thus, from the thio-ureas are formed the guanidines: SO \NHC 6 H 5 +NH3+Pb0=C = NH \NH The thio-amides react in the same manner with ammonia in the presence of mercuric chloride. SUBSTITUTIONS. 99 P. Methods for Obtaining Thio and Sulpho Compounds, and the Acid Esters of Sulphuric Acid. Substitution of by S. The pentasulphide of phosphorus is generally employed, but in the CO group the is also replaced by the action of hydrogen sulphide, aldehydes and ketones being thus converted into thio compounds. Benzophenone, (C6H 5 ) 2 CO at 100, with phosphorus penta- sulphide, P 2 S 5 , or with an alcoholic solution of ammonium sulphydrate, gives the mercaptan ((C 6 H 5 ) 2 C(SH)2. Amides are converted into thio-amides by phosphorus pentasulphide; but as the reaction is very energetic, and as there may be a liberation of hydrogen sulphide and the for- mation of nitriles, it is better to use the anilides. Thus, for- manilide, C 6 H 5 .NH.CHO, heated on a water-bath with P 2 S 5 , gives C 6 H 5 .NH.CSH. The cyanates, by the action of phosphorus pentasulphide, give sulphocyanides. The of the OH group is replaced by S only by the use of P 2 S5. Acetic acid gives thio acetic acid. With phenols, besides mercaptans, phosphorus pentasul- phide also gives esters of phosphoric acid. For example: 8C 6 H 5 .OH + P 2 S 5 - 2[PO(OC 6 H 5 ) 3 ] + 3H 2 S + 2C 6 H 5 .SH. For a description of the methods of replacing by the aid of P 2 S 3 , see previous pages. Substitution of halogens by S. The metallic sulphides are used for this purpose. Thus: 2CH 3 I +R 2 S = (CH 3 ) 2 S +2RI. But the products resulting from the action of phosphorus pentachloride on anilides may be converted into thio-anilides by the action of hydrogen sulphide (thus, the compound eHs is converted into thio-benzanilide) . 100 ORGANIC SYNTHESES. Substitution of halogens by HS. This is accomplished by heating the halogen with an aqueous or alcoholic solution of potassium sulphydrate: C 2 H 5 Br + KSH = C 2 H 5 .SH + KBr. Sometimes, with mercaptans, other sulphur compounds are obtained, according to the equation: 2RC1 + 2KSH = R 2 S + H 2 S + 2KC1. The chlorides of the carboxyl and sulphonic acids behave in the same manner with potassium sulphydrate. The halogen to be found in the aromatic nucleus is replaced by HS under the same conditions under which the OH group is replaced /(I) .Cl by NH 2 . Thus, nitro-dichlor-benzene, C 6 H 3 ^-(2) N0 2 , with \(4) Cl /(I) SH ammonium sulphide, givesCeH3^-(2) N0 2 . \(4) Cl Substitution of NH 2 by HS. In certain cases this can be realized by the aid of the diazo compounds. In fact, if ta /N v diazo-benzene sulphonic acid, C 6 HX /N, there is added an alcoholic solution of potassium sulphide, a liberal disengage- XSK mentof nitrogen takes place, and there is formed C 6 H 4 <^ OQ TT-J- the reaction also gives rise to the formation of various secondary products. Substitution of NH by S. This is brought about by the direct action of hydrogen sulphide; thus, 65 .x - * heated with hydrogen sulphide to 130 C, is converted into SUBS TITUTIONS. ' ', i E The reaction takes place better on heating amidines in a sealed tube with carbon disulphide: In the same manner the group N.R can also be replaced by S. Substitution of H by SO 2 .OH. This may be accomplished by the action of concentrated or fuming sulphuric acid, of the anhydride, or of chlorsulphonic acid, S0 2 (OH)C1. The mono- sulphonic acids of the aromatic hydrocarbons are obtained by treating the latter in the cold, and more rapidly by heat- ing with concentrated sulphuric acid. With chlorsulphonic^ acid, it is necessary to operate cold, or even with artificial refrigeration. The insoluble sulphonic acids are separated by the addition of a little water; they may be recrystallized from sulphuric acid not too dilute. For the soluble acids the acid liquor is diluted with water and saturated with carbonate of lead or barium, and the salts are purified by crystallization, after having removed the insoluble sulphate by_ filtration^ The salt is then decomposed with sulphuric acid or hydrogen sulphide. In order to separate the isomers, it is best to form the chlorides by treating with phosphorus pentachloride, and then the amides by the action of ammonia. After crystallization of the amides, the acids are set free by heating under pressure with hydrochloric acid. For compounds containing several sulphonic acid groups r it is better to use fuming sulphuric acid and heat, or, still bet- ter, to pass the vapors of the hydrocarbon into acid of 66 Be, heated. The anhydride, S0 3 , and chlorsulphonic acid, S0 2 (OH)Cl r at an elevated temperature, can give rise to sulphones; these are easily separated, owing to their insolubility in water. The halogen and nitro substitution products of the aromatic hydrocarbons behave with sulphuric acid like the hydrocar- ; ORGANIC SYNTHESES. bons themselves. (Bodies containing a halogen in the side- chain are carbonized with sulphuric acid.) Certain bromine and iodine compounds give with sulphuric acids certain higher halo- gen substitution products. Thus, dibrom-benzene, CeH^ W 5 r , gives tetrabrom- and hexabrombenzenes. 1 The amido compounds readily yield sulphonic acids on heating their sulphates, at 180-200 C, either simple or alco- holated, until water or alcohol is no longer set free. 2 Thus: C 6 H 5 .NH 2 .S0 4 H 2 =C 6 H 4 /^ s5H + H2 ' ^(2)NH 3 2 +C 2 H 5 .OH. \(5) S0 2 OH Both processes give good yields of the sulphonic acids. 3 A particular case for obtaining the amido-sulphonic acids consists in the action of ammonium hydrosulphide on the nitro compounds, a-nitro-naphthalene is converted into the ammonium salt of amido-naphthalene-sulphonic acid. The temperature is of great importance in the production of different isomers, particularly with the phenol sulphonic acids. Chlorsulphonic acid may be employed, acting on a solution of phenol in carbon disulphide. The carboxylic acids of the alphatic series are converted into sulphonic acids by the anhydride, S0 3 , or chlorsulphonic acid; in the aromatic series, fuming sulphuric acid is necessary, and also high temperatures. Sulphuric acid reacts with difficulty on the pyridine nucleus. With pyridine it is necessary to heat to 320 C. Also quinoline 1 The acid plays the part of the brominating agent. See Berichte, vol. 25, P. 1526. 2 The action of sulphuric anhydride on the aliphatic amines is to form sul- phaminic acids: C 2 H 5 .NH 2 +SO 3 =SO 2 <^ c H . 3 The sulphovinic esters of the amido compounds are obtained by the double decomposition of the calcium salts with oxalates of the bases. SUBSTITUTIONS. 103 gives a sulphonic acid in the benzene nucleus, but not in the quinoline part of the molecule. The saturated hydrocarbons and their halogen substitu- tion products do not react with sulphuric acid. The satu- rated alcohols, however, react; methyl alcohol with fuming sulphuric acid gives CH 2 (OH)S0 3 H and CH(OH)(S0 3 H) 2 . The anhydride, S0 3 , gives similar bodies by uniting, not with the carbon attached to the OH (except with CH 3 .OH), but with the neighboring atom: The amides and the nitriles, at the same time they are saponified, are also converted into sulphonic acids. Aceto- nitrile gives sulphacetic acid, which in its turn, under the influ- ence of sulphuric acid, is decomposed with liberation of car- bonic acid and the formation of the disulphonic acid of methane : CH 3 .CN + 3S0 4 H 2 = CH 2 (S0 3 H) 2 + C0 2 + S0 2 (OH) (O.N H 4 ) . Substitution of halogens by S0 2 .OH. This is an indirect way of obtaining the sulphonic acids of the aliphatic series. This reaction takes place by the action of sulphites on halogen compounds : CH 2 .C1 CH 2 .S0 3 .Na | +S0 3 Na 2 = +NaCL CO.OM CO.OM The ammonium salt may also be used. If ethyl iodide is heated with an aqueous solution of ammonium sulphite until complete dissolution, with ammonium iodide, there is formed at the same time C 2 H 5 .S0 3 .NH 4 . The mixture is diluted with water and boiled with lead oxide until ammonia ceases be to evolved ; and after filtering, in order to remove the iodide of lead, there is in solution the lead salt of the sulphonic acid, which only requires to be decomposed with hydrogen sulphide. If there is in the compound several atoms of a halogen, 104 ORGANIC SYNTHESES. these may be substituted totally or partially, according to the quantity of the salt used in the reaction. There may also be a reduction of the halogen. In the aromatic compounds, the halogen which is in the side-chain may also be replaced: *<(i) CTiBr+K^'-^S! CH,S0 3 K+ KBr - Brom-benzyl-bromide. In derivatives of phenol, quinone, etc., it is only partially replaced. Thus, trichlor-phenol with potassium sulphite gives dichlor-phenol-sulphonate of potassium and the chlor-phenol- disulphonate. The halogens united to nitrogen are easily replaced by sulphuric acid: the solution of the chloride, C6H4(OH)N:N.C1 (obtained by the addition of the theoretical quantity of so- dium nitrite to the cooled solution of the hydrochloride of ortho-amido-phenol), treated with potassium sulphite, gives Substitution of NH 2 by SO 3 H. This offers an indirect means of obtaining sulphonic acid derivatives, and is effected by passing N 2 3 into a concentrated alcoholic solution of the base, saturated with sulphurous acid : The diazo bodies behave in this manner on boiling with an alcoholic solution of sulphurous acid. Substitution of OH by S0 4 H. In the aliphatic series this is accomplished as readily as the substitution of H by S0 3 H in the aromatic series: CH 3 .OH+S0 4 H 2 = H 2 0+CH 3 .O.S0 2 .OH. Sulphuric acid reacts so energetically with the alcohols that it is necessary to mix them with caution; the reaction is finished by heating for a time on a water-bath. On diluting SUBSTITUTIONS. 105 with water, the excess of sulphuric acid is removed, as already explained. The free acids are obtained very easily by means of the lead salts which are decomposed by hydrogen sulphide. The acid esters of sulphuric acid are also obtained by adding gradually to chlor-sulphonic acid the theoretical amount of well-cooled alcohol: C 2 H 5 .OH + S0 2 .OH.C1 = C 2 H 5 .O.S0 2 .OH + HCI. The acid esters of the phenols are in general very unstable, and cannot be prepared by the action of sulphuric acid on phenols (/?-naphthol-sulphate, CioH 7 .O.S0 2 .OH, offers an exception, as it is formed by the -direct action of sulphuric acid). In order to prepare the corresponding alkali salts, potassium pyrosulphate is added to the concentrated aqueous solution of the alkali phenate, and heated for several hours at 60-70 C. The following equation may be taken as repre- senting the reaction: C 6 H 5 .OK + K 2 S 2 7 = C 6 H 5 .O.S0 2 .OK + S0 4 K 2 . If higher heat is used, the para-sulpho-phenol is formed. Substitution of H by S0 2 C1. This is accomplished by the action of sulphuryl chloride, S0 2 C1 2 , on the alcohols and secondary amines. By gradually adding the theoretical quan- tity of alcohol to sulphuryl chloride ~and cooling, an energetic reaction takes place, hydrochloric acid being liberated, while there is formed RO.S0 2 C1, in the form of a heavy oil, which is purified by washing with cold water and drying over potash. The action of sulphuryl chloride on the hydrochloride of dimethyl-amine gives (CH 3 ) 2 .N.S0 2 C1. Substitution of S0 3 H by OH. (See previous pages.) 106 ORGANIC SYNTHESES. G. Methods for the Preparation of Metallo-Organic Derivatives. The substitution of H by a metal occurs in the OH (also in SH), CH 2 , and NH groups. The hydrogen of alcoholic OH is replaced by the action of the alkali metals, and also (espe- cially with the polyatomic alcohols) by the action of the oxides of barium, calcium, and lead. In phenols the H of OH is replaced by the action of alkali metals. In acids, the hydrogen is readily replaced by a metal by double decomposition with the salts. In order to prepare the salts of potassium, sodium, calcium, barium, and strontium, the free acid is saturated by the corresponding base. The oxides of barium, calcium, and strontium may be used in excess, and afterwards removed by saturating with carbonic acid. If the salt is not soluble in alcohol, it may be precipitated from its aqueous solution by the addition of alcohol. The salts of potassium and sodium soluble in alcohol .may be prepared by saturating the alcoholic solution of the acid with the carbonates of potassium or sodium. The salts of the alkaline earth and heavy metals may be prepared by saturating the free acid with oxides of these metals, or by double decomposition of the alkaline or ammo- nium salts with barium chloride, acetate of lead, sulphate of copper, nitrate of silver, etc. This method is used for the preparation of insoluble or difficultly soluble salts. The silver salts of the aromatic acids are prepared more readily by double decomposition of the calcium salts with pure silver nitrate not containing any free acid. The calcium, barium, and lead salts are often prepared; in order to obtain the free acid it is simply sufficient to decom- pose these salts with oxalic acid, sulphuric acid, or hydrogen sulphide, after having purified them by crystallization. The silver salts, not containing any water of crystallization, serve especially well for the determination of the molecular weights SUBSTITUTIONS 107 C.OH -- > C/^ -- > CO I I I CO.OH CO.OH CO.OH CO.OH Glyceric acid. Pyruvic acid. It is to be remarked that the transformation of pyruvic acid from glyceric acid is analogous to the production of aldehyde by the dehydration of glycol. The ethers of the a-acids, in which OH plays the role of a tertiary alcohol, are likewise comparable to the alcohols. Thus, methyl-acrylic acid is obtained by the action of phos- phorus trichloride on the ether of a-oxy-isobutyric acid: 0. CH 2 .OH CH/ Phenyl-glycol. Phenyl-ethylene oxide. The removal of water from the ordinary glycols of the ali- phatic series (by means of dehydrating agents) is accompanied by the formation of isomerides. The compounds formed are not true anhydrides but isomers, from which the glycol can- not be again regenerated by the addition of water; thus, ordi- nary glycol gives ethyl aldehyde: CH 3 CH 2 .OH | I -- > c=o CH 2 .OH | H Glycol. Aldehyde. U4 ORGANIC SYNTHESES. To obtain the true anhydrides it is necessary to remove the elements of hydrochloric acid from the mono-chlorhydrins : CH< VXl 2 .Vyl V-LJ. 2 v | -HC1= | >0 CH 2 .OH CH/ Chlorhydrin of glycol. Ethylene oxide. The f-hydroxy acids, as remarked above, lose water when they are formed; on this account the lactones are always formed in their place. Thus, by the oxidation of isocaproic. acid, (CH 3 ) 2 .CH CH 2 there is obtained CH 2 C0.< .OH CO- Iso-caproic acid. Caprolactone. In the same manner, by the reduction of levulinic acid (a f-ke tonic acid), in place of obtaining the corresponding hydroxy acid, there is formed valero-lactone : CH 3 .CO CH CH 2 CO.OH CO Levulinic acid. Valero-lactone. The removal of water from the aromatic hydroxy acids (OH fixed to the benzene nucleus) takes place rather diffi- cultly; it is necessary to subject the body to dry distillation, or to the action of 'concentrated hydrobromic acid. In this manner it is possiole to obtain coumarin from coumaric acid. The dicarboxylic acids behave in the same manner as the REMOVAL OF RADICALS. 115 a-hydroxy-acids; by heating them, or by the action of dehy- drating agents, they are converted into anhydrides. The acids of the aliphatic series, which have two carboxyl groups, united the one to the other (as in oxalic acid), or with one or two .atoms of carbon (malonic acid and its homologues), do not give anhydrides, but are decomposed, giving rise to carbonic acid and a mono-basic acid: + CH 3 .CO.OH. Malonic acid. Acetic acid. In the aromatic series, the anhydrides are formed when the two carboxyl groups are in the ortho position with refer- ence to one another, or with reference to the point which unites two benzene residues. Simultaneously with the anhydride, there are formed, in certain cases, ketonic acids. Diphenic acid, moderately heated with concentrated sulphuric acid, gives diphenyl-ke tonic acid: C 6 H 4 .CO.OH C 6 H 4X I -* I >o C 6 H 4 .CO.OH C 6 H 3 < XXXOH. Some dicarboxylic acids are convered into anhydrides by a prolonged fusion, others by repeated distillations, and some by acetic anhydride or acetyl chloride. To remove the water, sulphuric acid may be used, and also the chlo- rides and oxy chlorides of phosphorus. When acetyl chloride is employed, it is necessary to remember that the hydroxy- dicarboxylic > acids give acetyl anhydrides, and the unsatu- rated di-acids are converted into chlorine derivatives of the desired acid. The ammoniacal salts of the acids, when heated, lose water and form the amides of the corresponding acids: R.CO.ONH 4 - H 2 - R.CO.NH 2 . Il6 ORGANIC SYNTHESES. Dry distillation is sufficient, but in the majority of cases the salt is dissociated, and is decomposed into the acid and ammonia. This is particularly so with ammonium acetate CHs.CO.ONELt, when there is only a yield of 25 per cent.; by distilling sodium acetate with ammonium chloride, the same result is obtained. Better results are obtained if the salt is heated in an autoclave for five or six hours at 220 C, when the yield is 80 to 85 per cent, of the theoretical. Some aro- matic acids give a slightly better yield than this. 1 In some cases (for example, in heating the ammonium salt of isobutyric acid) a secondary amide is formed simultaneously with the primary amide. The dica r boxylic acids, on heating, behave in the same manner: with the acid salts there are formed acid amides; with. the neutral salts, amides. The amido acids, on losing water, are converted into imides* This reaction sometimes takes place in attempting to form the acid amides. Thus, brom-succinic ester, heated with an. alcoholic solution of ammonia, gives the imide of aspartic acid, instead of asparagine: C 2 H 3 Br(CO.OH) 2 -> C 2 Brom-succinic acid. Asparagine. and Imido-aspartic acid. By the oxidation of ortho-sulpho-amidotoluene there is produced simultaneously amido-sulphobenzoic acid and the imide derivative, saccharin, a substance which has an exceed- ingly sweet taste: P /CH 3 p /CO.OH p /CO \ NH C6H4 \S0 2 .NH 2 C6H4 \S0 2 .NH ? CfiH4 \S0 2 / NH2 - Ortho-sulpho-amidotoluene. Amido-sulphobenzoic acid. Saccharin. 1 With respect to the time and temperature of the reaction for different acids, see Menchoutkine, Jour. Soc. Phys. Chim. Russe, vol. 16, p. 191, and vol. 17,. p. 259. REMOVAL OF RADICALS. 1 i 7 The amides, by the loss of water, are changed into nitriles: C 6 H 5 .CO.NH 2 gives C 6 H 5 .C^N. Benzamide. Benzo nitrile. It rarely happens that water may be removed from amides- by simply heating, but the intervention of a dehydrating agent is required (such as P 2 5 , PC1 5 , P 2 S 5 , and ZnCl 2 ). In order to obtain nitriles, one may start with the ammo- nium salt of the corresponding acid and treat it with phos- phoric anhydride. The aromatic nitriles are also obtained by the action of lead sulphocyanide on the acids: 2C 6 H 5 .CO.OH + Pb(CNS) 2 = 2C 6 H5CN + PbS + H 2 S + 2C0 2 . Benzoic acid. Benzonitrile. The ortho-amido-anilides (1.2), on losing water, give sub- stituted derivatives of the amidines: p TT (I) NH 2 TJ n p TT /N \p CeH4 (2) NH.CO.CH 3 ~ M2 = UH 4 C. The removal of water takes place at the moment of for- mation of ortho-amido-anilide (by the action of the chloride of the acid, or of the acid itself, on the ortho-diamido com- pound). Some apparent anhydrides are obtained with the derivatives of ortho-amido-phenol. Thus, CeH^ ~ ^C.CeHs is- prepared by the reduction of C 6 H 4 <^ Q QQ n jj > or is produced in the action of benzoyl chloride on ortho-amido-phenol. The aldoximes R.CH:N.OH, by the loss of water (with acetic anhydride), are converted into nitriles, RC:N. Some compounds containing nitrogen are easily decom- posed with loss of water. The oxidation of choline, Ii8 ORGANIC SYNTHESES. CH 2 .OH CO.OH , instead of giving | , furnishes CH 2 .N(CH 3 ) 3 OH CH 2 N(CH 3 ) 3 OH CO-0 the anhydride of betaine, | | CH 2 N(CH 3 ) 3 The diazo bodies of the phenols and the sulphonic acids lose water at the moment of their formation. For example, with the amido-sulphonic acid, p TT /S0 2 .OH UH4 \NH 2 ' in place of obtaining wehave C6 Nitro-amidobenzoic acid, C 6 H 3 (NH 2 )(N0 2 )CO.OH, in the same manner, with nitrous acid, gives: The nitrites of the secondary amines and of the esters of "the amido acids of the fatty series are very unstable com- pounds which decompose with loss of water, and the forma- tion of nitroso-amines and esters of the diazo-acids. Thus: C 8 H! 7 N.HN0 2 - H 2 = C 8 H 16 (NO)N. Nitroso-conine. CH 2 .NH 2 .HN0 2 CH< || | -2H 2 0= | X N C0 2 .C 2 Hs C0 2 .C 2 H5. Nitrite of glycocoll ester. Diazo-acetic ester. The nitrite of glycocoll may be obtained by double decom- position between the hydrochloride of the ester of glycocoll REMOVAL OF RADICALS. 119 (action of HC1 in absolute alcohol on the acid amide) with sil- ver nitrite. The ester of the diazo-acid is obtained by adding potassium nitrite to a solution of the hydrochloride of the ester of glycocoll; by the action of hydrochloric acid, there is a splitting-off of water and the formation of the diazo-com- pound. With the nitrite of aspartic ester there is obtained the ester of diazo-succinic acid: C(N = N)CO.OH .OH CHo.CO.< The diazo-acids of the aliphatic series are stable only in the form of esters or amides; when liberated they decom- pose with loss of nitrogen. By the removal of water from the ammonium compounds of the aldehydes, there may be obtained artificially the homologues and analogues of pyridine. Acrolein-ammonia on distillation gives picoline (/?-methyl- pyridine); with the ammonia derivative of crotonic aldehyde, collidine (methyl-ethyl-pyridine) is produced. The alkamine, (CH 3 ) 2 .C CH 2 NH/ \CH.OH, (CH 3 ) 2 .C-CH 2 , which is obtained by the reduction of triacetonamine, gives, with sulphuric acid, the poisonous alkaloid triacetonine : (CH 3 ) 2 .C CH NH/ NcH. (CH 3 ) 2 .C CH 2 By heating normal butyric acid with pentasulphide of phosphorus, using two to three times the theoretical quantity, there is formed thiophene, C 4 H 4 S. Its formation can be regarded 120 ORGANIC SYNTHESES. as a removal of water and hydrogen from the thio-butyric acid, CH 3 .CH 2 .CH 2 .CO.SH, which is at first formed. D. Removal of Ammonia, NH 3 . When the diamines and the diamides are heated they lose NH 3 and form imines and imides. Thus succinamide gives succinimide: CH 2 .CO.NH 2 CH 2 .C(X -NH 3 = | >NH. [ 2 .CO.NH 2 CH 2 .CO -"-. CH. The hydrochloride of ethylene-diamine is decomposed, when heated, into ammonium chloride and the hydrochloride of the imine: CH 2 .NH 2 .HC1 CH 2X | =NH4C1+ | >NH.HC1. CH 2 .NH 2 .HC1 CH/ By even distilling the hydrochloride of pentamethylene- diamine (reduction of the cyanide of trimethylene) there is formed, at the same time with ammonium chloride, some of the hydrochloride of piperidine: nTT /CH 2 .CH 2 .NH 2 .HC1 AT TT pi , PTT / CH 2 .CH2\ ATT T Tr CH2 \CH 2 .CH 2 .NH 2 .HC1 =NH4C1 +CH2 \CH 2 .CH 2 / NH - HCL E. Removal of Hydrogen Sulphide. The substituted thio-ureas lose hydrogen sulphide when treated with lead oxide, or with freshly precipitated mercury oxide. Thus: n . r /NH.CH 3 X1 2 O=^ X XT -2 Methyl-thio-urea. 'NH.C 6 H 5 > T H.C 6 H 5 Diphenyl-thio-urea. REMOVAL OF RADICALS. 121 The same thio-ureas of the aliphatic series may be obtained by heating the salts of the thio-carbamic acids (obtained by the union of CS 2 with RNH 2 ) with alcohol in sealed tubes to 110-120 C., thus causing a removal of hydrogen sulphide: KH.C 2 Hs _TT Q_ap/NH.C 2 H5 S.NH 3 .C 2 H 5 ^XNH.CaHs' The product obtained by the combination of diethyl- amine with carbon disulphide, /N(C 2 H 5 ) 2 U \S.NH 2 (C 2 H 5 ) 2 > is a stable enough compound in the sense that it does not lose hydrogen sulphide even when treated with metallic oxides, but it is decomposed into diethyl-amine and a salt of diethyl- thio-carbamic acid. The substituted dithio-carbamic acids are converted into isosulphocyanic esters by loss of hydrogen sulphide : .R SH As the acids themselves are not very stable, their lead or silver salts are used. In order to prepare the isosulphocyanates of the aliphatic series, it is not necessary to isolate the salts of the dithio-car- bamic acids; the mixture obtained by the union of the amine with carbon disulphide and the theoretical quantity of mer- curic chloride may be distilled directly. The product of the union of 2R.NH 2 with carbon disulphide may also be treated with an alcoholic solution of iodine. F. Removal of Sulphuric Anhydride (S0 3 ). The removal of S0 3 takes place by heating the sulphonic acids with water; with hydrochloric and hydrobromic acids to 150-250, and by the dry distillation of the sulphonic 122 ORGANIC SYNTHESES. acids. This reaction is very often employed for the purifi- cation and separation of the hydrocarbons, C n H 2 n- 6 ; the best means of conducting this decomposition is with superheated steam. The dry salt of the sulphonic acid is mixed with 3 parts of sulphuric acid and 1 part of water and heated to 180-220 C.; there is then passed a current of superheated steam through the mixture. G. Removal of Carbon (C). This is a very rare reaction; the only example, perhaps, is the formation of protocatechuic aldehyde, C 7 H 6 3 , from piperonal, C 8 H 6 03, by heating this body in a sealed tube with hydrochloric acid: /CHO /CHO C 6 H 3 (-0\ rn =C 6 \0/ C \OH Piperonal. Protocatechuic aldehyde. Another example of this removal would be nitrophthalide, C 8 H 5 N04, that Dussar is said to have obtained by the action of potash and calcium hydrate on nitronaphthalene, Ci H 7 N0 2 ; but in reality there may be only a removal of the impurities in the nitronaphthalene, and it is doubtful if nitrophthalide is formed. 1 H. Removal of Carbon Monoxide (CO). The aldehydes and ketones, on energetic heating, lose CO. Thus benzoic aldehyde, C 6 H 5 .CHO, gives benzene, C 6 H 6 ; benzo- phenone, C 6 H 5 .CO.C 6 H 5 , and acetophenone, C 6 H 5 CO.CH 3 , are transformed, the first into diphenyl, C 6 H 5 .C 6 H5, the second into toluene, CeH 5 .CH 3 . This reaction is not very complete as there is formed a large amount of other products. 1 See Fehling's Handworterbuch, Bd. V, p. 508, and Jour. Soc. Phys. Chim. Russe, vol. 2, p. 266. See also Annalen, vol. 202, p. 219. REMOVAL OF RADICALS. 123 I. Removal of Carbonic Acid (C0 2 ). The monocarboxylic acids of the formula R.COOH, by losing C0 2 , give the hydrocarbons, RH; it is only necessary to heat them with the hydrates or oxides of calcium or barium. The dicarboxylic acids of the aliphatic series lose C0 2 much more easily, and are converted into a monocarboxylic acid when the two COOH groups are attached to a single carbon atom. Such are malonic acid and its substituted derivatives. Thus, methyl-malonic acid (iso-succinic) is split up into carbonic and propionic acids: CH 3 \ /\J\J.\JQLi5 l>< H 2 (X XJO.OH \ Pyruvic acid, heated with dilute sulphuric acid, loses C0 2 and gives the aldehyde : CH 3 .CO.CO.OH - C0 2 - CH 3 .COH. Phenyl-glycidic acid, C 9 H 8 3 = CH' CO.OH at the ordinary temperature, is decomposed with liberation of C0 2 . J. Removal of Formic Acid (HCO.OH). Hydrophthalic acid, C 8 H 8 4 , with sulphuric acid, gives phthalic acid, at the same time with benzoic acid, carbon monoxide, and water : C 8 H 8 4 = C 7 H 6 2 + CO + H 2 0. REMOVAL OF RADICALS. 127 K. Removal of Acetic Acid (CH 3 .CO.OH). (See Chapters VII and VIII.) L. Removal of a Hydrocarbon. This reaction occurs in the decomposition of the esters of the alcohols. The action of phosphoric anhydride on phenols also takes place in the same manner. Thymol, for example, is decomposed into propylene and meta-cresol : C 6 H 3 ^(3) OH 3 - \4) C 3 H 5 M. Removal of Alcohol (R.OH). In a body which readily loses water, if the hydrogen of the OH group is replaced by a radical R, for example, C 2 H 5 , it is almost certain that the compound will be decomposed with loss of alcohol. The hydrates of substituted ammonias behave in the same manner; on heating them, they are decomposed into a compound in which the nitrogen is triatomic, and into an alcohol, or the products of its decomposition, hydrocarbon and water. N. Removal of Simple Ethers. The halogen products of the ammonium compounds, like RiNI, are decomposed by strong heat into NR 3 and IR. If the four radicals are not identical, and if they include a CH 3 group, the latter will combine with the halogen. O. Removal of Amines (NH 2 R). The symmetrical urea compounds are decomposed by the action of acids into isocyanic esters and amines : ' = CO.N.C 2 H 5 + NH 2 .C 2 H 5 . 128 ORGANIC SYNTHESES. The thio-ureas behave in the same manner, and this reac- tion is utilized for the preparation of iso-sulphocyanides of the aromatic series; the reaction also takes place in the aliphatic series, but it is not made use of. In the aromatic series, the thio-ureas are heated with sul- phuric or hydrochloric acid; it is better, however, to use a con- centrated solution of phosphoric acid (sp. gr. = 1.7), two or three parts of this solution to one part of the thio-urea. After heating for a short time, the iso-sulphocyanate is volatilized with steam, and in the residue the amine is removed with an alkali. Diphenyl-thio-urea is thus completely deomposed : When the thio-ureas contain two different radicals, there are obtained two sulphocyanides and two amines, the decom- position being effected in two directions : CS/NjHp ^\|NHR'| CHAPTER V. DIRECT FIXATION OF GROUPS. I. GENERAL CONSIDERATIONS. IN the direct fixation of halogen acids l to unsaturated hydrocarbons, the halogen attaches itself to the carbon atom having the least amount of hydrogen. 2 In cases where two atoms of carbon may be equal in this respect, the halogen combines with that one to which a methyl group (CH 3 ) is attached : (CH 3 ) 2 C = CH 2 with HC1 -> (CH 3 )2CC1.CH 3 . 1 See Markovnikoff and A. Zaytzeff as referred to on p. 108. See also Kablukoff, On the Triatomic Alcohols and their Derivatives, Moscow, 1887 (in Russian). 2 Among the unsaturated hydrocarbons, those containing a carbon atom at- tached to the least number of hydrogen atoms combine the most readily with the halogen acids. This property may be used for the separation of isomers. Thus, the two isomeric amylenes (CH 3 ) 2 .CH.CH=CH 8 Iso-propyl-ethylene and Methyl'-ethyl-ethylene cannot be satisfactorily separated by distillation, as the former boils at 21 C. and the latter at 32 C. At 20 C., however, the latter alone gives the iodo-com- pound: and this boils at above 100 C. 129 130 ORGANIC SYNTHESES. With hydrocarbons having the group C=C , two atoms of the halogen are fixed to the carbon atom with the least hydrogen. CH 3 .C^CH withHCl-* CH 3 .CG1 2 .CH 3 . Aldehydes and unsaturated acids, by the fixation of a halo- gen acid, most often form the /^-substituted body of the saturated compound : CH 2 : CH.CO.OH + HC1 = CH 2 .C1.CH 2 CO.OH. Acrylic acid. ^-chlor-propionic acid. CH 2 : CC1.CO.OH + HC1 = CH 2 C1.CHC1.CO.OH. C \ With oxides containing the | />O group, the halogen attaches itself to the carbon atom with the most hydrogen, and the OH group, which is formed, to the carbon atom with the least hydrogen: CH HO.OC.CH 2 \0 + HC1 = CH 2 .C1.CH(OH) .CO.OH. It is possible to obtain in this manner the iodo substitution products of the alcohols: + HI=CH 3 .CH(OH).CH 2 L In the fixation of the halogen acids to the unsaturated alco- hols, there is a displacement of OH by halogen (see page 79). With hydrobromic acid, there are often two isomers formed; by modifying the conditions it is possible to direct at will the reaction in one way or the other. In the majority of cases the reaction proceeds normally (the bromine being fixed by the carbon atom with the least hydrogen) if the hydrobromic acid is not very concentrated. Thus, brom-ethylene, with acid satu- DIRECT FIXATION OF GROUPS. 131 rated at 6 C., gives mostly ethylene bromide, CH 2 Br.CH 2 Br; but if the acid is diluted with two volumes of water, ethylidene bromide is formed, CH 3 .CH.Br 2 . The temperature of the reac- tion also exerts an influence: thus, atropic acid (a-phenyl- acrylic), CH 2 = C(C 6 H 5 ).CO.OH, at 100 C., with concentrated hydrobromic acid, gives /?-brom-hydratropic acid; but at the ordinary temperature, a mixture of the a- and /9-acids is ob- tained. The carbon atom to which the halogen attaches itself, in the case of the fixation of a halogen acid, is the same one as that to which the OH group attaches itself in the case of the fixation of water. II. FIXATION OF HYDROGEN (H). (See under Chapter II.) III. FIXATION OF OXYGEN (0). To the reactions already mentioned in Chapter I, there will be added here the case of the fixation of oxygen to com- pounds containing sulphur, nitrogen, or metals. The sodium mercaptan, C 2 H 5 .SNa, with dry oxygen, com- bines with 2 and is converted into C 2 H 5 .S0 2 Na. The same mercaptan, as well as other bodies of the type R.SH, are oxi- dized by nitric acid, and by the fixation of 3 give the acids R.S0. 2 OH. The .sulphur compounds R 2 S are oxidized equally by nitric acid or potassium permanganate; by regulating the concentration and temperature, it is possible to fix or 2 and to obtain the oxides SOR 2 or the sulphones SO 2 R2.* Iso-propyl-pseudonitrol, (CH 3 ) 2 C(NO)N0 2 (see page 83), oxi- dized with chromic acid, is converted into dinitro-isopropane, (CH 3 ) 2 .C(N0 2 ) 2 (?); but it is not possible to affirm that there is here a conversion of the NO group into N0 2 . It may be that there are several successive reactions, as, for example, in the 1 See A. Zaytzeff, Action of Nitric Acid on some Organic Compounds contain- ing Sulphur, Kasan, 1868 (in Russian). I3 2 ORGANIC SYNTHESES. transformation of quinone-oxime (nitrosophenol, see page 83) into nitrophenol: /N.OH OH /N /OH C 6 H 4 < | +^ H =C 6 H 4 < N \OH M} \OH Quinone-oxime. Nitrophenol. Many metallo-organic compounds readily combine with oxygen and form oxides : (C 2 H 5 ) 3 Sn (C 2 H 5 ) 3 Sn v + 0= >0. (C 2 H 5 ) 3 Sn (C 2 H 5 ) 3 Sn/ When zinc-ethyl is slowly oxidized in ethereal solution, there is formed Zn (C 2 H 5 ) 2 0, and finally zinc ethylate (C 2 H 5 0) 2 Zn. IV. FIXATION OF HALOGENS. A. The Fixation of Chlorine (Cl). This takes place directly with unsaturated compounds, such as ethylene. Chlorine or the trichloride of antimony is used, or the body is slightly heated with a mixture liberating chlorine (Mn0 2 with NaCl and H 2 S0 4 ). Sometimes with chlorine there are formed substitution products; this reaction is indicated by the evolution of hydrochloric acid gas. It is necessary to take into account the part played by light in the action of chlorine. Thus, a-propylene chloride, CH 3 .CC1 = CH 2 , in the dark gives substitution products; in the light, an addition product. The unsaturated compounds, when brominated or iodinated, likewise fix chlorine, the latter with replacement of iodine by chlorine. For example, allyl iodide, CH 2 = CH.CH 2 I, with chlorine, gives the trichlorhydrin of glycerol: CH 2 C1.CHC1.CH 2 C1. Phenyl iodide does not lose iodine, but gives an addition pro- duct, CeHsI.Cl^ by the action of chlorine on its solution in chloroform. In order to fix chlorine to alcohols, ethers, etc., which are DIRECT FIXATION OF GROUPS. 133. unsaturated, the method of procedure is to pass a current of chlorine gas into their solution in carbon disulphide. B. Fixation of Bromine (Br). In order to fix bromine to unsaturated gaseous hydro- carbons, they are passed into liquid bromine, covered with a layer of water, until the bromine is decolorized. The reaction may also be carried out by using a large vessel filled with the gas and provided with a reservoir of bromine. The bromine is- added drop by drop, and the flask is shaken well; the gas may be led in continually from a gasometer. This method of opera- tion is a good one for the fixation of bromine by ethylene. For liquid substances bromine water may be used, or the bromine itself may be added directly to the well-cooled substance, if necessary diluting with carbon disulphide, chloroform, ether ,, or glacial acetic acid; the bromine being added drop by drop until the red color of an excess of bromine is noticeable. With solid bodies it is best to shake their solutions in one of the above- named solvents with bromine. 1 If an excess of bromine is- undesirable, a quantity of bromine slightly less than the theo- retical is taken. In order to avoid a violent reaction, the substance is placed under a watch-glass with a vessel con- taining the theoretical amount of bromine, so arranged that the compound is brominated by the absorption of the bromine vapors. If the substance is easily oxidized, it is necessary to- dry it carefully. There sometimes arise secondary reactions: iodine compounds not only fix bromine, but also exchange their iodine for bromine; and the unsaturated acids, in fixing bromine with liberation of hydrobromic acid, may give brom- inated lac tones. Compounds having the C=C group can take up Br 2 and the first with ease, and the latter with more difficulty. Para-nitrophenyl-propiolic acid, C 6 H 4 / /^c c = CCOOH' 1 See A. Verigo, Direct Fixation in the Azo-benzene Group, Odessa, 1871 (in Russian). 134 ORGANIC SYNTHESES. takes up Br2. The reaction may be so energetic that there is sometimes a decomposition of the body, and, even by the regu- lated action of bromine in theoretical amount, it is impossible to avoid the formation of some tetrabromide. C. Fixation of Iodine (I). This takes place with more difficulty than that of chlorine or bromine. Compounds containing C =C only take up I 2 , and even that with but little energy. For example, to combine tolane C.C 6 H 5 with iodine, it is necessary to heat their mixture to C.C 6 H 5 fusion. In order to fix iodine, either the gaseous body is passed over iodine, or the substance is treated with the latter dissolved in carbon disulphide, chloroform, or potassium iodide. The iodides of the ammonium compounds combine readily with iodine. Thus, NRJ.I2 and NR 4 I.I 4 are formed by adding an alcoholic solution of iodine to a solution of NR 4 I. V. FIXATION OF HALOGEN ACIDS. Hydrobromic acid is fixed with more difficulty than hydri- odic acid, but less readily than hydrochloric acid. The action of hydrochloric or hydrobromic acid takes place either at the ordinary temperature or by heating in sealed tubes. In place of the aqueous solutions of the acids, their solutions in glacial acetic acid may at times be used. When using hydrobromic acid, it must not be forgotten that there may also be a splitting-off of HBr; and, if the com- bination contains chlorine, this may be replaced by bromine. Concentrated hydriodic acid acts either cold or hot, either at the ordinary pressure or in sealed tubes. It must be borne in mind that this acid also acts as a reducing agent. Thus, allyl iodide, CaHsI, with hydriodic acid, gives CsHe^, which is partially reduced to isopropyl iodide, (CH 3 ) 2 CHI, and partially DIRECT FIXATION OF CROUPS. 135 decomposed into propylene, CH 36 and I 2 . In order to treat volatile liquids with hydriodic acid, Lagermark proceeds as follows: In a tube is placed some phosphorus iodide, a glass capsule containing the theoretical quantity of water, and a small tube containing the substance; the tube is sealed and placed in a refrigerating mixture, the capsule is broken, and when the tube is removed from the cooling mixture the reaction is finished. VI. FIXATION OF WATER. The fixation of water to hydrocarbons of the ethylene and acetylene series takes place through the agency of sulphuric acid. At first there is formed an addition product with sul- phuric acid (H and O.SC^OH, which add themselves like H and halogens in the case of halogen acids), which is decom- posed by water into an alcohol in the case of ethylene deriva- tives, and into an aldehyde or a ketone (anhydrides of dihy- drates) in the case of acetylene compounds. The hydrocarbon is easily and quickly absorbed by the sulphuric acid (2 to 3 parts of acid to 1 part of water). It is necessary to cool the mixture well, otherwise there may be a polymerization. Sulphuric acid also allows of the fixing of water to com- pounds containing double or triple bonds between carbon atoms : C.C 6 H 5 CO.C 6 H 5 Tolane. Desoxy benzoin. The unsaturated acids of the acrylic series are converted into oxy-acids. Oleic acid, Ci8H 34 02, gives oxy-stearic acid, Ci 8 H 3 5(OH)0 2 . When there should be obtained ^-oxy-acids by the action of sulphuric acid on unsaturated acids, lactones are formed instead. The salts of mercury permit of the convenient addition of water to the derivatives of acetylene (method of KoutcherofT) . l 1 Jour. Soc. Phys. Chim. Russe, vol. 15, p. 575. 136 ORGANIC SYNTHESES. Dilute nitric acid furnishes a means of adding water to the unsaturated compounds. It is in this manner that isobutylene is converted into tertiary butyl alcohol; croton aldehyde, among other products, gives aldol. There may also be obtained the hydrate of terpene by this method. The elements of water may also be fixed directly; fumaric acid, heated with water to 150-180 C., gives malic acid. The oxides and anhydrides of acids containing the group add the elements of water by boiling their aqueous solu- tions, or simply by exposure to the air at ordinary temperatures. The ease with which the elements of water are affixed de- creases with increase in the molecular weight. Oxides containing a tertiary radical, such as CH 3 .CH V I >, (CH 3 ) 2 C / readily affix water even in the cold. 1 For hydrolysis accom- panied by reduction, see under Chapter II. The anhydrides of poly car boxy lie acids are converted into acids, some by the action of water, and others only by the a tion of alkalies or alkaline carbonates; some of these acids, when their salts are decomposed, are converted into anhydrides and water. Coumarin affixes water through the medium of alkalies, and gives an acid isomeric with coumaric acid, existing only, however, in the form of a salt; alkalies convert these salts into the corresponding salts of coumaric acid. Nitriles, by affixing water, are converted into amides. R.C E= N + H 2 = R.CO.NH 2 . In neutral liquids, the fixation of water takes place slowly and incompletely; to increase the speed of the reaction it is necessary to use an alkaline or an acid medium. It is generally 1 Jour. Soc. Phys. Chim, Russe, vol. 14, p. 355; and Prjibuitek, On the Organic Dioxides, St. Petersburg, 1887 (in Russian). DIRECT FIXATION OF GROUPS. 137 customary to use an excess of dilute hydrochloric or sulphuric acid, and to heat, if necessary, in a sealed tube. It must be borne in mind that with an energetic reaction, as with acids or alkalies, the amide in its turn is partially, and sometimes entirely, converted into the acid. Often, even for the preparation of carboxylic acids, in place of the amide, the nitrile may be used directly. Some nitriles, especially in the aromatic series, are very unstable. Thus, (1)OH (2) CN is converted into salicylic acid simply by prolonged fusion with alkalies; the nitrile, C 6 (CH 3 ) 5 .CN, is not converted into the acid. The nitriles may be saponified by means of hydriodic acid, but reduction often takes place. One of the best means of obtaining hydro-atropic acid consists in saponifying the product of the action of HCN on acetophenone : C 6 H 5 \^/OH CH 3 which, on saponification, changes OH into H and gives /OH.CO.OH. Oxlj In order to convert the nitriles R.CO.CN into amides without forming acids, they are treated in the cold with the theoretical amount of fuming hydrochloric acid. Cyanogen in aqueous solution is converted almost entirely into oxamide by the addition of a small quantity of aldehyde. This reaction may be explained by the successive formation and destruction of a dihydrate. 1 1 It is interesting to recall that this fact was discovered by Liebig while search- ing for a synthesis of malic acid by means of aldehyde and nascent oxalic acid (see J. Liebig's and Wohler's Brief wechsd, Bd. II, p. 78). I3 8 ORGANIC SYNTHESES. Hydrogen peroxide also converts nitriles completely into amides with liberation of oxygen. Thus : C 6 H 5 .CN + H 2 2 = C 6 H 5 .CO.NH 2 + 0. Some nitriles affix the elements of water with particular ease. If moist cyanogen chloride is passed through an ethereal solution of meta-nitraniline, there is at first formed a nitrile which subsequently affixes water and is converted into nitro- phenylurea : (I) N0 2 p n /N0 2 r N.C 6 H4.N0 2 (3) NH 2 " bell4 " Meta-nitraniline. Nitrile. Nitrophenyl-urea. The amides, R.CO.NH 2 , by the fixation of water, give the ammonium salts, R.CO.ONHi. This reaction has been con- sidered as a replacement of NH 2 by OH (Chapter I) . The iso-nitriles by the fixation of water are converted into substituted derivatives of f ormamide CH v 0|H OH| | >N+ + -H 2 CH/ H H Some iso-nitriles absorb water with so much energy that they convert glacial acetic acid into acetic anhydride. The imides, by the fixation of water, give acid amides; it is sufficient to heat them with baryta-water or lime-water, and in some cases with ammonia. The imide of aspartic acid (see page 116) gives asparagine : The Fixation of Hydrogen Peroxide (HO. OH). This occurs with ethylene and gives ethylene glycol. Oxidation accom- DIRECT FIXATION OF GROUPS. 139 panied by hydration is another thing than the fixation of the elements of hydrogen peroxide (see chapter on Oxidation) . The Fixation of Hydrogen Sulphide (H 2 S). This occurs with nitriles in the formation of thio-amides. The nitrile in alco- holic solution is treated with ammonium sulphydrate at the ordinary temperature, or by heating in sealed tubes. The Fixation of Sulphurous Anhydride (S0 2 ). This occurs, for example, with zinc-ethyl : Zn(C 2 H 5 ) 2 + 2S0 2 = (C 2 H 5 .S0 2 ) 2 Zn. For the preparation of the sodium salt of sulphinic acid, see under Chapter I. Benzene sulphinic acid, C 6 H 5 .SO.OH, occurs as the result of the addition of S0 2 to C 6 H 5 in the presence of aluminium chloride. The Fixation of Bisulphites (MHS0 3 ). This occurs readily with aldehydes, the oxide of ethylene and its analogues. The Fixation of Sulphuric Anhydride (see page 103) . The Fixation of Sulphuric Acid (see page 135) . VII. FIXATION OF AMMONIA (NH 3 ). Many aldehydes combine with ammonia to form hydroxy amines : X \NH 2 ' The method of carrying out this reaction is to pass a cur- rent of ammonia gas through a cooled solution of the aldehyde in ether or chloroform, or to add to the aldehyde an alcoholic or aqueous solution of ammonia. In the same manner, the unsaturated acids can unite with ammonia; cro tonic acid, C4H 6 2 , heated in a sealed tube (100- 115 C.), with an aqueous solution of ammonia, forms /?-amido- butyric acid, C 4 H 7 (NH 2 )0 2 . 140 ORGANIC SYNTHESES. Carbonic anhydride combines with two molecules of am- monia, giving the ammonium salt of carbamic acid : m /NH 2 \O.NH 4 . Carbon disulphide, heated with ammonia in aqueous or alcoholic solution, forms some sulphocyanide and some sulphy- drate of ammonium, but these products may be considered as coming from the decomposition of the ammonium thiocar- bamate which is at first formed : pc ,/NH 2 V;D\ ri ATTJ = v>iN O .li -TL4 T~ -Cl 2 io . \O.I\Xl4 The iso-cyanic esters and the iso-sulphocyanides combine with ammonia to give substituted derivatives of urea and thio-urea. The nitriles combine with ammonia to give amidines. For substituted derivatives of the amidines, see previous pages. The combination of hydroxylamine with nitriles gives amido- oximes or oximes : ,/NH 2 VIII. FIXATION OF OXIDES OF NITROGEN AND NITROSYL CHLORIDE. 1 By passing nitrous anhydride (arsenious acid and concen- trated nitric acid) into a cooled acetic solution of amylene, the body C 5 Hio.N 2 04 is formed. This is considered as a deriva- tive of trimethyl-ethylene, and without doubt has the formula : C CH 3 . O.N0 2 .N.OH 1 See Wallach, Annalen, vols. 239, 241, 245, and 248; also N. Bunge, On Nilroso Derivatives, Kieff, 1868 (in Russian); and Jour. Soc. Phys. Chim. Russe, vol. 1, p. 257. DIRECT FIXATION OF GROUPS. 141 With a nitrite and acetic acid it is possible to affix N 2 3 . Terpene yields a crystalline body (nitrosite?) : ' Nitrosyl chloride combines in the same manner with terpene to give CioHispj* , when it is passed into a solution of terpene in chloroform cooled to 10 C., or when concentrated hydrochloric acid is allowed to act on a cooled mixture of terpene and nitrous ether. All these compounds are charac- terized by the ease with which the groups, O.N02 and O.NO, as well as Cl, are replaced by ammonia, amines, potassium cyanide, etc. IX. FIXATION OF HYPOCHLOROUS ACID (Cl.OH). 1 Hypochlorous acid, in reacting with unsaturated compounds, gives nearly always two iso-merides. With acrylic acid, CH 2 = CH.CO.OH, for instance, it gives: CH 2 C1.CH(OH).CO.OH and CH 2 (OH).CHC1.CO.OH. Often the OH of hypochlorous acid is attached to the same carbon atom as the Cl when reaction with this acid occurs. The reaction with hypochlorous acid is carried out in the following manner: Freshly precipitated oxide of mercury is mixed with water, and chlorine is passed into the mixture during constant stirring; then a fresh quantity of mercury oxide is added. This solution of hypochlorous acid may be used directly, or it is distilled in a strong current of carbon dioxide gas in 1 See P. Melikoff, On Derivatives of the Isomeric Crotonic Acids, Odessa, 1885 (in Russian); and Jour. Soc. Phys. CTiim. Russe, vol. 19, p. 524; also C. Refor- matsky, Polyatomic Alcohols, Kasan, 1889 (in Russian). 142 ORGANIC SYNTHESES: order to carry off the chlorine. When the reaction is finished the excess of hypochlorous acid is removed by the addition of sodium hyposulphite. Hypochlorous acid may be replaced by calcium hypochlorite to which boric acid is added. The fixation of hypochlorous acid is employed especially for the preparation of chlorhydrins of the polyhydric alcohols. CHAPTER VI. FIXATIONS ACCOMPANIED BY A DECOMPOSITION OF THE MOLECULE. I. FIXATION OF WATER (HYDRATION). A. Hydration followed by a Rupture of Carbon Bonds. MANY of the aromatic ketones, fused with potash or distilled with soda-lime, are decomposed into hydrocarbons and salts of the acids: C 6 H 5 .CO.|C 6 H 5 + H OK = C 6 H 6 + C 6 H 5 .CO.OK. It is necessary at times to employ boiling alcoholic potash. Anthraquinone is converted into benzoic acid by fusion with potash at 250 C. : [ 4 + 2HOK = 2C 6 H 5 .CO.OK. Diketones (see page 126) are readily decomposed with the addition of water by boiling with alkalies or acids, and yield ketones and carboxylic acids: CH 3 -CO ^OH = CH 3 .CO.OH " H ~C 6 H 5 .CO.CH 3 C 6 H 5 .CO.CH 2 A certain quantity of the diketone is also decomposed at the other keto group, yielding the corresponding acid and ketone : CH 3 .CO.CH 2 CH 3 .CO.CH 3 143 144 ORGANIC SYNTHESES. The ketonic acids, like aceto-acetic acid and its derivatives, with concentrated solutions of the alkalies, are decomposed with the formation of carboxylic acids. Thus, aceto-acetic acid, or its ester (which is saponified during the reaction), yields two molecules of acetic acid; and benzyl-ace to-acetic acid (or its ester) gives benzyl-acetic acid (hydrocinnamic acid) and acetic acid: OH CO.CHs HO.OC.CH 3 TJ nTi/ CH^.CeHs ^TT / CO.OH 2 \CO.OH ' In the same manner, by heating carboxylic and hydroxy- acids with dilute sulphuric acid, they are decomposed into formic acid, aldehydes, and ketones. Some of them are decomposed on heating with caustic potash. Thus, a-oxy-isobutyric acid: (CH 3 ) 2 .C.OH OH (CH 3 ) 2 .CO + -H 2 = CO.OH H H.CO.OH. Phenyl-lactic acid, heated to only 130 C., is decomposed into formic acid and phenyl-aldehyde : C 6 H 5 .CH 2 .CH.OH OH C 6 H 5 .CH 2 .CHO + -H 2 = X3.0H H H.CO.OH. C Citric acid is decomposed in an analogous manner, when it is moderately heated with concentrated sulphuric acid, into formic acid and keto-dicarboxylic acid: CH 2 .CO.QH I /ICQ.OH+ H| I \OJ"H +OH| CH 2 .CO.OH The latter reactions may be regarded as a splitting-off of formic acid. FIXATIONS WITH DECOMPOSITION. 145 Unsaturated compounds, by the addition of water (boiling with water, dilute acids or alkalies), can be split at the posi- . tion of the double link. Mesityl oxide furnishes acetone, and benzoyl-acrylic acid gives aceto-phenone and glyoxylic acid : (CH 3 ) 2 C OH OH (CH 3 ) 2 .CO || + + -H 2 = CH 3 .CO. CH H H CH 3 .CO.CH 3 . C 6 H 5 .CO. CH H H C 6 H 5 .CO.CH 3 || + + -H 2 = CH OH OH CHO C0.< CO.OH CO.OH The rupture may also take place at a point other than that of the double link. For instance, /?-trichlor-acetyl-acrylic acid, by boiling with baryta-water, is decomposed into chloroform and f umaric acid : C.C1 3 H CH.CO OH = CHC1 3 + CH.CO.OH. II * II CH.CO.OH CH.CO.OH For cases of a rupture of the carbon bonds without a rup- ture of the molecule, see page 138. B. Hydration followed by a Rupture of a Bond between Carbon and Oxygen. The oxides of alcohol radicals, either the same or different, are decomposed by the fixation of water when they are heated with dilute mineral acids. Thus: C 2 H 5 .O.C 2 H 5 gives 2C 2 H 5 OH. The true esters are only decomposed with difficulty with water alone, and even then but incompletely. In the cold, ethyl acetate, CH 3 .CO.OC 2 H 5 , is slightly decomposed by water; 146 ORGANIC SYNTHESES, at 100 C., after six hours' boiling, the decomposition is not very great. The saponification takes place more rapidly by the action of acids and caustic alkalies; the latter are mostly employed. The rapidity of the decomposition of the ester depends on its nature, as well as on the acid or alkali employed,, and the conditions of the experiment. To saponify esters they are heated with an excess of potash or soda, baryta, or lime; the oxides of lead and magnesium are also used. To accelerate the reaction, it is sometimes. necessary to add alcohol. The end of the reaction is recognized by the disappearance of the ester, which is difficultly soluble in water. If an alkaline solution is used, the alcohol is removed by steam, or by agitation with a suitable solvent. The liquid is then acidulated, and, if the acid does not separate, it is removed by a solvent. If the acid gives a difficultly soluble salt, with a metal precipitable with hydrogen sulphide, such a. salt may be prepared and subsequently decomposed by hydrogen sulphide. For acids difficultly soluble in water, their barium salts may be prepared and subsequently decomposed with sul- phuric acid. Esters allow of a convenient method for the preparation of substituted products of the alcohols and acids. Thus, malonic ester, CH2(CO.OC 2 H 5 )2, treated with chlorine, is converted inta chlor-malonic ester, CHC1(CO.OC2H 5 )2, which is decomposed in /PO OTT the cold by alkalies into chlor-malonic acid, CHC1<^ p^ OH' and alcohol; if heat is employed, the hydroxy compound tar- tronic acid, CH(OH)', is formed. To saponify the esters of the aromatic nitro-acids, it is necessary to dilute acids, for the action of alkalies gives rise to azo compounds. Certain precautions must be taken with ke tonic acids; in certain cases, as, for example, with C 6 H5.CO.CH2.CO.OC 2 H5 r it is necessary to use sodium carbonate for the saponification, as caustic alkalies cause a more extensive decomposition. FIXATIONS WITH DECOMPOSITION. 147 The anhydrides of the carboxylic acids are slowly decom- posited by the action of water, and more rapidly by alkalies. The anhydrides of the sulphonic acids are decomposed with a little more difficulty. The carbohydrates, C^H^On and C 6 Hi 5 , take up water when heated with dilute acids, and are decomposed into several other carbohydrates. The glucosides are decomposed in the same manner by hydrolysis with dilute acids and the action of certain ferments. C. Hydration followed by a Rupture of a Bond between Carbon and Nitrogen. The substituted derivatives of the amides (anilides), heated in a sealed tube with water or with concentrated acids (HC1 and H 2 S04) , combine with water and are split up into carboxylic acids and amines: C 6 H 4 CLNH.CO.H + H 2 = C 6 H 4 CLNH 2 + H.CO.OH. Chlor-formanilide. Chlor-aniline. This reaction is a limited one. 1 Solutions of alkalies and ammoniacal alcohol react in the same manner, but with more difficulty. The compounds formed by the action of aldehydes on ammonia and amines (see page 139) are decomposed by hydroly- sis (heating with HC1) into their components. Bodies of the formula, R.CH = NR', double their molecule when heated with water. The decomposition of the iso-nitriles into formic acid and amines recalls that of the substituted derivatives of form- anilide. Alkalies hydrolyze the iso-cyanic esters, and decompose them into carbonic acid and amines. The iso-sulphocyanides 1 See Menchoutkine, Jour. Soc. Phys. Chim. Russe, vol. 14, p. 274. 148 ORGANIC SYNTHESES. behave in the same manner. Thus, C 6 H 5 .NCS, heated with concentrated sulphuric acid (or, for example, hydrochloric acid acting on an alcoholic solution of the body), combines with water and gives C 6 H 5 .NH 2 , and COS. H. FIXATION OF AMMONIA. The decomposition of simple and compound esters by ammonia into amines and alcohols takes place but rarely : R.O.R + NH 3 = NH 2 R + R.OH. The esters of the ortho- and para-nitrophenols, r H /(I) O.CH 3 nH r H /(I) O.CH 3 CeH4 \(2) N0 2 and CeH4 \(4) N0 2 , heated to 200 C., with an aqueous solution of ammonia, give methyl alcohol and the corresponding nitro-anilines. The true esters of the dicarboxylic acids are decomposed by ammonia into amides and alcohols, and they react with either one or two molecules of ammonia. If there be added the theoretical quantity of an alcoholic solution of ammonia to a cooled solution of oxalic ester, there is formed the ester of oxamic acid; with an excess of ammonia, oxamide is obtained: CO.OC 2 H 5 CO.OC 2 H 5 CO.NH 2 CO.OC 2 H 5 CO.NH 2 CO.NH 2 Oxalic ester. Oxamic ester. Oxamide. Ammonia reacts readily with the esters of the substituted acids. When a-chlor-propionic ester is agitated with ammonia,, it is converted into CH 3 .CHCLCO.NH 2 . The reaction takes place in the cold, otherwise the chlorine would be replaced by NH 2 . The anhydrides of the monobasic acids are decomposed FIXATIONS WITH DECOMPOSITION. 149 more or less easily by ammonia with the formation of amides. The imido-esters react very easily with ammonia to form ami- dines : CHAPTER VII. CONDENSATIONS. I. CONDENSATION BY DIRECT ADDITION. SOME of the unsaturated hydrocarbons readily combine with acids to form esters of the alcohols. Thus, amylene (trimethyl-ethylene) combines with acetic acid and other acids. 1 The hydrocarbons, Ci Hi 6 , heated with glacial acetic acid, are converted into esters of borneol and its isomerides. Anhydrides, such as ethylene oxide, easily form with acetic acid esters of the corresponding glycols : CH2. CH 2 .OH | >0+C 2 H 3 O.OH= | CH/ CH 2 O.C 2 H 3 Ethylene oxide. Mono-acetic ester of glycol. Ethylene oxide also combines with glycol, and even its own molecules polymerize. The anhydrides of the dibasic acids behave in the same manner. Thus, succinic anhydride, by boiling with absolute alcohol, is converted into .the ester of succinic acid : CH 2 .CO V CH 2 .CO.OH >0+C 2 H 5 .OH= | CH 2 .CCK CH 2 .CO.OC 2 H 5 Aldehydes react with the anhydrides and chlorides of the acids to give derivatives of the dihydrates. Thus: C 6 H 5 .CHO + (C 2 H 3 0) 2 = Ce Benzaldehyde. Acetic anhydride. J3enzylidene diacetate. 1 See Jour. Soc. Phys. Chim. Russe, vol. 20, p. 594. 150 CON DENS A TIONS. I 5 1 Some aldehydes combine directly with the amines and amides: cenanthylic aldehyde with aniline gives a body the formula of which is, undoubtedly, C6Hl3 ' CH \NH.C 6 H 5 ' Ordinary aldehyde gives the following compound with acetamide : 'OH ^ NH.C 2 H 3 The polymerization of aldehyde can be considered as the combination of several molecules of aldehyde. However, it may also be the result of several reactions (formation at first of a hydrate, then removal of water). Thus, paraldehyde can be represented as the combination of three molecules of the dihydrate united with the loss of 3H 2 0: \>j i, CH 3 )H o x o }H.CH 3 . It is possible that the crystalline polymeride of ethylene oxide is formed from glycol in the same manner. Compounds which contain several atoms of carbon and nitrogen, united with several bonds, generally combine easily with several other molecules. Thus, cyanic acid and the iso-cyanic esters combine with alcohols and various ammonia derivatives. By heating the fol- lowing ester with ethyl alcohol in sealed tubes to 100 C., C 2 H 5 .N=CO, we have Ethyl ester 9f Ethyl ester of iso-cyanic acid. ethyl-carbamic acid. 152 ORGANIC SYNTHESES. With cyanic acid 1 the reaction takes place in the cold, the carbamic esters (urethanes) formed by the excess of cyanic acid are converted into allophanic esters : Urethane. Ethyl allophanate. The iso-cyanic esters combine very readily with primary and secondary amines with the formation of substituted deriva- tives of urea. Thus, iso-cyanic ester is converted into di-ethyl- urea by the action of water, the molecule of ethylamine formed reacting with the ester : C 2 H 5 .N: The iso-cyanic esters combine in the same manner with diamines and amides. In the first case, according to the quan- tity of iso-cyanic ester, there is a combination between one or two molecules : [H(1)C 6 H 4 (2)NH 2 ^HS Ortho-phenylene-diamine. /(I) NH 2 , pH N . m m /NH(l)C 6 CeH4 \(2) N H 2 +C 2 H *- N ' CC =CO \NH.C 2 H, or: CH 2 .NH 2 CH 2 .NH.CO.NH.C 2 H 5 | +2C 2 H 5 .N:CO=| CH 2 .NH 2 CH 2 .NH.CO.NH.C 2 H 5 In order to obtain monosubstituted ureas, instead of using free cyanic acid, potassium cyanate may be treated with the salt of the amine; the solution of the two substances in water is evaporated to dryness, and the residue is taken up with alco- hol. The cyanate formed in this reaction is converted so rapidly 1 Therefore, according to this reaction, cyanic acid behaves like a carbimide. CONDENSATIONS. 153 by isomerization into a substituted urea that one cannot be sure of its formation. The iso-sulphocyanides, like the iso-cyanic esters, when treated with alcohols and rnercaptans, combine with them: C 6 H 5 .N: CS + C 2 H 5 .SH The iso-sulphocyanides also combine with amido com- pounds, and are converted into derivatives of thio-urea. The reaction proceeds very easily, it being even necessary to mod- erate it by diluting the reacting bodies with a suitable liquid, alcohol, for example. Sulphocyanic acid, when treated with amines, gives salts which are much more stable than the corresponding salts of cyanic acid. Thus, sulphocyan-ethyl-amine, CNSH.NH 2 .C 2 H 5 , does not give ethyl-urea when heated. But the salts of the aromatic amines give the corresponding thio-ureas. The nitriles combine with alcohols and mercaptans, giving imido-esters and imido-thio-esters. Thus: The reaction does not occur by the direct combination of the two bodies; it is necessary to pass a current of hydrochloric acid gas through a well-cooled mixture of equi-molecular parts of the two bodies. Under these circumstances there is sub- sequently formed, with the nitriles of the aliphatic series, a compound of the imido-ester with hydrochloric acid. It is necessary to carefully avoid excess of alcohol, or the following reaction will take place : CH \0 C 2 H 5 ' HC1 + 2C 2H 5 OH =CH(O.C 2 H 5 ) 3 +NH 4 C1 Ortho-formic ester. In order to decompose the hydrochloric acid compound of the imido-ester, it may be treated with an alcoholic solution 154 ORGANIC SYNTHESES. of ammonia, or it may be dissolved in ether and shaken with a solution of caustic soda. The unsaturated nitriles take up HC1 at the same time CH 2 they form imido-esters. Thus, allyl-cyanide, || , CH.CH 2 .CN treated with alcohol and HC1, gives CH 3 The nitriles combine with amines to form substituted deriva- tives of the amidines. The reaction is brought about by heating the nitrile with a salt of the amine in a sealed tube : Cyanogen (nitrile of oxalic acid) reacts at the ordinary temperature with amine compounds. Two NH 2 groups enter into the reaction; that is to say, two molecules of a mono- amine and a single molecule of a body containing two NH 2 or NH groups. Thus, by passing cyanogen into an alcoholic or ethereal solution of aniline, two molecules of the latter combine with one molecule of cyanogen: CN C 6 H 5 .NH.C:NH I = CN C 6 H 5 . 2C 6 H 5 .NH 2 + | = } .NH.C:NH But if a compound containing two NH groups is taken, the equation becomes: /NH.C 6 H 5 CN /N(C 6 H 5 )C:NH C 6 H 5 .N:C< +| =C 6 H 5 .N:C<( | . \NH.C 6 H 5 CN X N(C 6 H 5 )C:NH Triphenyl-guanidine. CON DENS A TIONS. 1 5 5 The reaction of CN.CN with amido-benzoic acid takes place between an equal number of molecules. Cyanimide and its derivatives behave like a nitrile, and in reacting with amido compounds they yield derivatives of guani- dine. Thus: C 6 H5.NH 2 .HC1+CN.NH 2 =C^-NH.C 6 H 5 .HC1. \NH 2 The diazo derivatives of the amido-sulphonic acids, by react- ing with phenols, oxycarboxylic acids, or amido derivatives, form azo compounds (azo-colors) . Thus: N.C 6 H4.S0 2X N.C 6 H4.S0 2 .OH | >0+C 6 H 5 .OH=|| N - / N.C 6 H 4 .OH The reaction is carried out by taking the theoretical quan- tity of the diazo compound prepared in advance, or the end product of the action of sodium nitrite on sulphanilic acid, C 6 H 4 C 6 H 7 0(O.C 2 H 3 0) 4 C1. Dextrose. Aceto-chlorhydrin. In certain cases, in order to obtain the esters the acid chloride is allowed to act on an alcoholate. 2 Thus, the esters of cyanic acid, N=C.OC2H 5 , are obtained by the action of cyanogen chloride on an alcoholate dissolved in an excess of alcohol. The esters are also formed by the reaction of the salts of the carboxyl acids (and, in the same manner, the thio-acids) and their derivatives with halogen compounds. 3 Generally, the chlorine or bromine compound is allowed to react on the alkaline salt of the acid, or the iodine derivative on the silver salt. The silver salt, moistened with the corresponding acid, is gradually heated with RI; a certain quantity of the product escapes during the reaction, but this may be avoided by taking an excess of silver salt. In certain cases it is necessary to dilute the reagents in ether in order to moderate the reaction. The anhydrides of the acids are obtained with difficulty by the action of acid chlorides on the acids. Thus, the reaction, C 6 H 5 .CO.C1 + C 6 H 5 .CO.OH = C 6 H 5 .CO.O.CO.C 6 H 5 + HC1, only takes place by heating in a sealed tube, and even, in any case, only about 50 per cent, of the theoretical yield is obtained. 1 See A. Colley, On Grape Sugar, Moscow, 1869 (in Russian). 2 The chlorides of the sulphqnic acids, R.SO 2 .C1, behave like those of the carboxylic acids; with alcohols and the alcoholates they yield the corresponding esters. Sometimes it is sufficient to evaporate the alcoholic solution to obtain the ester; but in other cases, a prolonged boiling is required or zinc dust is used, as, for example, in the reaction of R.SO 2 .C1 on the phenols. The action of the chloride of the sulphonic acids may be moderated (particularly CgH^SO^Cl) by dissolving them in ether, or by adding the alcoholate in an excess of alcohol. 3 In the same manner are produced the esters of the dihydric alcohols. See ~L Tuttschew, On Glycols in General and on a New Compound, Carvol-dibenzoate, St Petersburg, 1858 (in Russian). 1 62 ORGANIC SYNTHESES. A good method of obtaining the anhydrides is the action of dehydrated oxalic acid on acid chlorides, or the action of the latter on the salt of the acid. 1 In place of using the ready- prepared chloride, the direct action of phosphorus oxychloride (1 molecule) on the salt of the acid (4 molecules) may be used. The reaction takes place in two phases: 2CH 3 .CO.OM + PC1 3 = PM0 3 + MCI + 2CH 8 .CO.C1, 2CH 3 .CO.C1 + 2CH 3 .CO.OM = 2MC1 + 2CH 3 .CO . O.CO.CH 3 . The anhydrides of the acids are also obtained by the action of the acid chloride on the nitrate of lead or silver, and also by the action of carbonyl chloride on the sodium salt of the acid : 2C 2 H 3 O.ONa + COC1 2 = (C 2 H 3 0) 2 + 2NaCl + C0 2 . Sodium acetate. Carbonyl Acetic anhydride. chloride. (2) Formation of Ethers, etc., with Liberation of Water. The direct formation of simple or mixed ethers (oxides of the alcoholic radicals), with elimination of water, takes place only with difficulty and always incompletely. With ethyl alcohol, the ether is obtained by energetic heating with a sul- phate or a chloride, although it may be considered that . the ether is formed through the action of the acid liberated in the decomposition of the salt. Benzhydrol, (Cells) 2 .CH. OH, is readily converted into the corresponding ether, [(C 6 H 5 ) 2 CH] 2 0; the alcohol of fluorene, CeKjv | >C /eiy \ H.OH, gives the ether, ( | >CH 0, \C 6 H/ / 2 by simple fusion; the alcohol of cumene, C 6 H4(C 3 H 7 )CH 2 .OH, containing traces of inorganic substances (one or two drops of 1 With the chlorides of the polycarboxylic acids there may be a secondary reaction on account of the splitting off of water. CONDENSATIONS. 163 sulphuric acid, for example), is decomposed on distilling into the ether [CeH^CaH^CHakO and water. (For the ethers of the dihydrates, see previous pages.) The methods employed in the aliphatic series do not always hold with the phenols, and it is necessary to use dehydrating agents. Thus phenol, heated with zinc chloride, gives a small quantity of the ether (C 6 H 5 ) 2 0. Resorcin, at 180 C., with fuming hydrochloric acid, gives the corresponding ether of resorcin, (C 6 H4.0H) 2 0. The anhydrides of the mono carboxylic acids are obtained with difficulty, even by the action of strong dehydrating agents. Glacial acetic acid with phosphoric anhydride gives a small quantity of acetic anhydride. For its preparation there may be employed an iso-nitrile (see page 138). The formation of the esters by the use of alcohols and acids takes place much better, but the reaction, R.CO.OH + R'.OH = R.CO.OR' + H 2 0, is never complete ; as soon as there is an equilibrium established between the decomposition of the acid ester and the water on the one hand, and the formation of the ester on the other hand, the reaction stops. The point of equilibrium depends on the nature of the alcohol and ester. It is necessary to use an excess of the reagents and to remove the water which is formed at the same time as the ester. This is usually accomplished by passing a current of dry hydrochloric acid gas through a mixture of the alcohol and acid, and heating from time to time. The esters of the phenols are formed by the action of phos- phorus oxychloride on a mixture of the phenol and acid, there being a liberation of hydrochloric acid. With polyhydric alcohols, according to circumstances, it is possible to replace one or more hydrogen atoms of the OH groups. The anhydrides of the acids react more readily than the 164 ORGANIC SYNTHESES. acids with alcohols, even without heating and in the absence of dehydrating agents; and in the majority of cases the reac- tion is complete. They are employed in the preparation of esters to replace the acid chlorides when the latter react with difficulty or give secondary products. In the case of acetic anhydride, its action is increased by the addition of dehydrated sodium acetate. The acetals (ethers of the dihydrates) are obtained by heat- ing aldehydes with alcohols: CH 3 .CHO + 2C 2 H 5 .OH = CH 3 .CH(OC 2 H 5 ) 2 + H 2 0. The reaction takes place at 100 C., if to a mixture of the aldehyde (1 part), and the alcohol (3 parts), there is added glacial acetic acid ( J part) ; as a secondary product there is formed some acetic ester, which is removed by heating in a closed vessel with caustic potash ; the acetal formed being dehydrated with calcium chloride. A better yield of acetal is obtained by passing a current of non-inflammable hydrogen phosphide into a mixture of alcohol and aldehyde, cooled to 21 C. The polyhydric alcohols behave in the same manner with aldehydes as the monohydric alcohols. Acetals are generally obtained by the oxidation of the cor- responding alcohols. 1 (3) Formation of Esters, etc., with Liberation of Ammonia or Nitrogen. The amides of certain acids can be converted into esters with liberation of ammonia by the action of alco- hols in the presence of acids. Thus : NH 2 .CHO + C 2 H 5 .OH + HC1 = CHO.OC 2 By boiling urea with a large quantity of propyl alcohol, we have: 1 By the oxidation of a mixture of methyl and ethyl alcohols, there is ob- tained, not the mixed acetal, CH 3 .CH(OCH 3 )(OC2H 5 ), but a mixture of methyl and ethyl acetals. CONDENSATIONS. 165 For the preparation of ortho-esters (ortho-formic ester) y by the reaction of imide-ethers on alcohols, see page 153. The diazo-compounds may be converted into esters under certain conditions. Thus, by decomposing the aromatic diazo- derivatives with acetic acid, the acetic esters of the phenols are obtained : CeH4 \N : N.S0 4 H The esters of diazo-acetic acid, on boiling with alcohol, give the esters of e thy 1-gly colic acid : CH<|| CH 2 .OC 2 H 5 | X N +C 2 H 5 .OH=| CO.O.C 2 H 5 CO.OC 2 H 5 B. Preparation of Compounds containing Sulphur. Sulphuretted compounds may be obtained by the action of chlorine compounds (or salts of the sulphonic acids) with the corresponding mercaptides, RSM l : CC1 4 + 4C 2 H 5 .SNa - C (SC 2 H 5 ) 4 + 4NaCL Sulphuretted compounds containing two similar R groups are obtained directly by the action of the chlorine compounds on potassium sulphide, K 2 S. The tertiary halogen derivatives, as, for example, tertiary iso-butyl iodide (CH 3 ) 3 C.I, do not form sulphur compounds with potassium sulphide, for generally there is a decomposition of the halogen compounds. Among the aromatic halogen deriva- 1 The acid chlorides react with the mercaptans themselves. Thus, CgH^SH heated with acetyl chloride, CH 3 .CO.C1, liberates hydrochloric acid and gives the ester of thioacetic acid, CH 3 .CO.S.C2H 5 . 166 ORGANIC SYNTHESES. tives there are some in which the halogen is replaced by HS by treatment with potassium sulphide. Sulphur compounds similar to those of the dihydrates are formed by the condensation of aldehydes and ketones with mer cap tans and thio-gly collie acid. By passing hydrochloric acid into a mixture of mercaptan and acetone, there is formed aceto-ethylmercaptol : 1 (CH 3 ) 2 CO + 2C 2 H 5 .SH = (CH 3 ) 2 C/^p 2 ^ 5 + H 2 0. Compounds containing S 2 are formed by the action of halogen compounds on M 2 S 2 ; and by the removal of hydrogen from mercaptans and thio-acids with the aid of oxidizing agents (gaseous oxygen, ferric chloride, chromic and nitric acids, hydro- gen peroxide, etc.); thus: is converted into | . C 6 H 5 .S The preparation of compounds containing S 2 , by the action of sulphuric acid on mercaptans, takes place according to the following equation : 2C 2 H 5 .SH + H 2 S0 4 = (C 2 H 5 ) 2 S 2 + S0 2 + 2H 2 0. By the action of iodine on C 2 H 5 .SNa, the disulphide of phenyl, (C 6 H 5 ) 2 S 2 , is formed. The sulphones, R.S0 2 .R, are formed by heating an aromatic sulphonic acid with an aromatic hydrocarbon in the presence of a dehydrating agent, such as phosphoric anhydride; they are also obtained by the action of sulphuric anhydride on a hydrocarbon, and by the action of sulphochlorides or aromatic hydrocarbons in the presence of aluminium chloride. Thus: C 6 H 5 .S0 2 C1+C 6 H 6 = S 1 By oxidizing with potassium permanganate there is formed a disulphone, (CH 3 ) 2 C(SO ? .C 2 H 5 ) 2 , called sulphonal, which has a physiological action some- what analogous to chloral. CONDENSATIONS. 167 The sulphones are also obtained by the action of halogen compounds on the salts of the sulphinic acids: C 2 H 5 .S0 2 Na + C 2 H 5 .Br = S0 2 p 25 + NaBr . For the preparation of sulphones by the oxidation of sulphur compounds, see under direct fixation of oxygen. C. Formation of Compounds containing Nitrogen. (1) AMMONIA DERIVATIVES. (a) Derivatives formed with Liberation of Halogen Acids or other Acids or Salts. The amines react with halogen compounds in the same manner as ammonia (see page 93), and are converted into secondary amines, and even tertiary amines, with an excess of the halogen compound. The secondary iodides, in their action on amines, yield hydro- carbons together with secondary amines. For example, isopropyl- iodide (CH 3 ) 2 CH.I, with isopropyl-amine (CH 3 ) 2 CH.NH 2 , is converted into [(CH 3 ) 2 CH] 2 .NH and propylene, CH 3 .CH:CH 2 . In order to separate the substances so formed, the mixture is treated with nitrous acid, and, by the nitrosamine thus pro- duced, the secondary amine is removed. The amido-acids react with chlorine compounds, and, accord- ing to the conditions of the reaction, there is a substitution of one or two atoms of hydrogen in the NH 2 group. By heating one molecule of para-amido-benzoic acid, CeH^ ,^ QQ with a solution (3 mols.) of caustic soda in alcohol and two molecules of methyl iodide, there is obtained dimethyl-para- A u -A n TI /(I) N(CH 3 ) 2 amido-benzoic acid, CetUC )^< ^Q QJJ . Amines with cyanogen chloride give substituted cyanamines. The reaction is brought about by passing cyanogen chloride into an ethereal solution of the amine : CNC1+ C 6 H 5 .NH 2 = C 6 H 5 .NH.CN + HC1. 1 68 ORGANIC SYNTHESES. With an excess of amine, a guanidine substitution product is formed. The acid chlorides react energetically with amido compounds, as do also the sulpho-chlorides, R.S0 2 .C1 : CH 3 .S0 2 .C1 + 2C 6 H 5 .NH 2 = CH 3 .S0 2 .NH.C 6 H 5 + C 6 H 5 .NH 2 HCL The substituted amides so formed (for example, the anilides) do not present a basic character. As to the manner in which the acid chlorides behave with ortho-diamines, see page 117. Carbonyl chloride, COC1 2 , with secondary diamines, behaves in the same manner as other acid chlorides; there is a substitu- tion of H by COC1, and the formation of special chlorides derived from urea, which in their turn, when heated with the diamine, give substituted derivatives of urea. Thus : (C 6 H 5 ) 2 NH + COC1 2 = (C 6 H 5 ) 2 N.COC1 + HC1. (C 6 H 5 ) 2 N.COC1 + (C 6 H 5 ) 2 NH = CCX + HCL The primary amines of the aromatic series yield disub- stituted ureas, which in their turn, when heated a long time with carbonyl chloride, give isocyanic esters : O \NH CeH + COCl2 = 2C 6 H 5-NCO + 2HC1. Phenyl-isocyanate, C 6 H 5 .NCO, may be obtained in the same direct manner by passing carbonyl chloride over the fused chlo- ride of the amine : C 6 H 5 .NH 2 .HC1 +COC1 2 = 2C 6 H 5 .NCO +3HC1. In the aliphatic series, the isocyanic esters are obtained by the distillation of RI or R.HS0 4 with the cyanates. CONDENSATIONS. 169 (b) Ammonia Derivatives formed with Liberation of Water. The primary aromatic amines become secondary, and the secondary tertiary, when they are heated with alcohols of the aliphatic series. Thus: C 6 H 5 .NH 2 + CH 3 .OH = C 6 H 5 .NH.CH 3 + H 2 0. The higher alcohols of the aliphatic series, with dehydrating agents, give substituted derivatives of the R group in the hydrogen of the benzene nucleus. The phenols react with the amines when heated to 250- 300 C. in the presence of the chlorides of zinc or calcium. The diphenols react more readily; for example, resorcin or hydro- quinone with aniline react at 300 C. with dehydrating agents: C 6 H4(OH) 2 + C 6 H 5 .NH 2 = C 6 H4(OH) NH.C 6 H 5 + H 2 0. With ortho-diamines, pyrocatechin gives phenazines; for example, when heated for some time with ortho-phenylene- diamine, it gives the phenazine identical with the azo-phenylene, Ci 2 H 8 N 2 , of Rasenack and Glaus: CoH.4\ yCoH.4. \N/ In this case, there is a removal of H 2 at the same time as a removal of water. The a-oxynitriles react easily with amido compounds. If the cyanhydrate of methyl-salicyl aldehyde is heated with an alcoholic solution of ammonia to 60-70 C., there is at first obtained the nitrile of an amido-acid, which then reacts again on the cyanhydrin in excess, as indicated by the following: 'OCH 3 /OCH 3 \OH NH 2 170 ORGANIC SYNTHESES. The carboxylic acids readily react with amines to form at first salts, which by loss of water give substituted amines. If an aqueous solution of methylamine and formic acid is distilled, there is formed methyl-formamide : HCO.OH + CH 3 .NH 2 = HCO.NH.CH 3 + H 2 0. Benzyl-acetamide is obtained by heating benzylamine with glacial acetic acid; acetanilide is obtained by a similar process 1 (see page 175). By heating equal molecules of acid and amine the reaction is not complete, for the water formed causes the decomposition of the substituted- derivatives of the amine (see page 147) ; in order to increase the yield, it is necessary to take an excess of acid. In certain cases, the reaction is made more complete by heating in sealed tubes, or by the use of dehy- drating agents. For example, in order to prepare chlor-acet- anilide, the chlor-acetate of aniline is treated with phosphoric anhydride : C 6 H 5 .NH 2 .HO.OC.CH 2 C1 - H 2 = C 6 H 5 .NH.CO.CH 2 .C1. Without this assistance there would probably be formed phenyl- glycocoll, CH 2 (NH.C 6 H 5 )CO.OH, with liberation of hydro- chloric acid. Diamido compounds react with either one or two molecules of acid. For the manner in which the ortho-diamines behave with acids, see page 117. Dicarboxylic acids form two series of derivatives, according to the number of molecules taking place in the reaction. By 1 The substituted derivatives of the amides can be obtained by the action of. the amines on the esters, alcohol being liberated. The substituted derivatives of the aromatic amines (anilides) are formed in some cases by the action of" phenol on the amine: C 10 H 7 (/?)OH+CH 3 .CO.NH 2 =CH 3 .CO.NH.C 10 H 7 +H 2 0. CON DENS A TIONS. 1 7 1 heating aniline with an excess of oxalic acid, the derivatives of oxamide are obtained : CO.OH CO.NH.C 6 H 5 | +2C 6 H 5 .NH 2 =| CO.OH CO.NH.C 6 H 5 +H 2 0. With equal molecules of acid and base, a derivative of oxamic acid is formed : CO.OH CO.NH.C 6 H 5 | +C 6 H 5 .NH 2 =| +H 2 0. CO.OH CO.OH Some substituted derivatives of the amido-acids at the temperature at which they are formed decompose into water and a substituted derivative of an imide : CH 2 .CO.NH.C 6 H 5 CH 2 .CO V | -H 2 0=| >N.C 6 H 5 . CH 2 .CO.OH CH 2 .CO/ The anhydrides of the acids behave in the same manner as the acids when treated with amines. They are used when the NH 2 group is substituted with difficulty in the acid radical, or when it is necessary to avoid a long heating, which is neces- sary when the acid is used. The reaction with anhydrides can be moderated by using a suitable solvent, or it may be increased by means of a dehydrating agent, such as fused sodium acetate. With amido-phenol, the acid group of the anhydride does not only act on the NH 2 group, but also on the OH (see page 164). For ortho-amido-phenol, see page 117. The aldehydes react with one or two molecules of amido compounds, with the liberation of water and the formation of a single or double bond between the carbon and nitrogen. 1 Thus benzaldehydes react with aniline as follows : C 6 H 5 .CHO + NH 2 .C 6 H 5 = C 6 H 5 .CH : N.C 6 H 5 + H 2 0. 1 For the action of aldehydes on aromatic amines, see p. 196. I7 2 ORGANIC SYNTHESES. Ordinary aldehyde behaves in the same manner with meta- amido-benzoic acid, forming: (1) CO.OH (3) N:CH.CH 3 ' There may at first be formed an addition product, R.CH(OH). NH.R' (see page 151), which is then decomposed with loss of water. Ordinary aldehydes react with two molecules of primary or secondary amines. 1 On mixing one molecule of aldehyde with two molecules of aniline, the following reaction takes place : CH 3 .CHO + 2C 6 H 5 .NH 2 = CH 3 .CH(NH.C 6 H 5 ) 2 + H 2 0. The aromatic aldehydes condense with ortho-diamines with liberation of 2H 2 (2 mols. of aldehyde and 1 mol. of ortho- diamine). The compound so formed is not a simple substi- tution of the hydrogen of the ammonia by 2R"; it is called aldehydine, and is a derivative of the amidines (see page 154). Thus, by the action of benzaldehyde on ortho-phenylene- diamine, we obtain benzaldehydine : C 6 H \ = C.C 6 H 5 In this reaction there is a simultaneous reduction and oxida- tion of benzaldehyde. Glyoxal, and compounds containing two CO groups in 1 The formation of such compounds as ammonia-acrolein and hydrobenzamide can be explained by admitting that they are the result of a condensation between the aldehyde and the addition products of ammonia: + C 6 H 5 .CHO= CON DENS A TIONS. 1 7 3 the ortho position (benzil, phenanthraquinone, etc.), combine with ortho-diamines to give quinoxalines: 1 CHO H 2 N CH=Nv >C 6 H4+2H 2 0. = N/ Quinoxaline. | + CHO H 2 N Bodies containing the CO group react in the same manner as aldehydes 2 with bodies containing NH 2 . The anilides, heated with amines and phosphorus trichloride, give substituted deriva- tives of the amidines : CH 3 .CO.NH.C 6 H 5 + C 6 H 5 .NH 2 = CH 3 .C/ 5 + H 2 0. As the anilide is prepared by the action of the acid on the amine, it is possible to obtain the substituted derivatives of the amidines by heating together the amine and acid with phosphorus tri- chloride. Urea condenses (with liberation of water) with various compounds. By heating it with isodialuric acid (obtained by the conversion of the condensation product of aceto-acetic 1 Hinsberg (Annalen, vol. 237, p. 327) reserves the name of quinoxalines to compounds which contain the nucleus: at the end of a chain of hexagonal nuclei, ancl gives the name of azines to those which contain the same nucleus in the midle of such a chain: Quinoxaline. Azine (diphenazine). * For the condensation of amines with carbohydrates, see W. Sorokine, Action of Qlucose on Aniline and Toluidine, Kasan, 1887 (in Russian). 174 ORGANIC SYNTHESES. ester with urea) and concentrated sulphuric acid, uric acid is produced : l C 4 H4N 2 4 + CO.N 2 H4 = CsILJ^Oa + 2H 2 0. The formation of uric acid under these conditions leads to the following formula for this body : NH-C.HN X I II >0. CO C.HN/ NH CO (c) Ammonia Derivatives formed with Liberation of H 2 S, Bodies containing the CS group react with amines in the same manner as bodies containing CO. Thus, diphenyl-thio-urea in alcoholic solution condenses with aniline in the presence of a metallic oxide to yield triphenyl-guanidine : <\TTT N? Carbon disulphide with aromatic amines gives substituted derivatives of thio-urea with liberation of hydrogen sulphide. Thus aniline heated with carbon disulphide and alcohol (with an inverted condenser) gives C \NH.C 6 H 5 ' For the action of carbon disulphide on the aliphatic amines, see under removal of hydrogen sulphide. 1 See Annalen, vol. 251, p. 235. CONDENSATIONS. 175 (d) Ammonia Derivatives formed with Liberation of NH 3 . The primary amines, on heating, are frequently converted into secondary amines: R.NH 2 + R.NH 2 = R 2 .NH + NH 3 . This reaction is facilitated by adding some substance capable of absorbing ammonia, such as calcium chloride or zinc chloride,, or acids. Dianthramine is readily formed by heating anthramine r Ci 4 H 9 .NH 2 , with boiling glacial acetic acid; as a secondary product there is formed aceto-anthramine : C 14 H 9 .NH.CO.CH 3 . The best method of obtaining certain secondary amines is to heat the amine with its hydrochloride : C 6 H 5 .NH 2 + C 6 H 5 .NH 2 .HC1 = (C 6 H 5 ) 2 NH + NH 4 C1. In this manner secondary amines may be obtained with different radicals, and also secondary acid amides. The reaction between an amine and an acid amide takes place readily. If acetamide is heated with aniline until ammonia is no longer disengaged, acetanilide is obtained in theoretical amount. Urea behaves in the same manner; heated with aniline or its hydrochloride, it gives phenyl-urea: fused with an excess of meta-amido-benzoic acid, it gives uramido-benzoic acid: FH 2 LC 6 H 4 .CO.OH. 1 76 ORGANIC SYNTHESES. With an excess of amine, urea gives disubstituted ureas. In some cases the NH group of amidines react with amines; for example : (2) DERIVATIVES OF THE DIAMINES R(NH 2 )2 AND THE DIIMIDES R(NH) 2 . (a) Substituted Hydrazines. The hydrazine substitution products (symmetrical) are obtained from phenylhydrazine by the action of bromine compounds, acid chlorides, acid anhy- drides, and acid amides. Phenylhydrazine condenses with aldehydes and ketones with liberation of water, this being a characteristic reaction for this body. With benzaldehyde, for example, it gives C6H5.CHiN.NH.C6H5. 1 The unsaturated aldehydes and ke- tones give hydrazine derivatives, which on distillation lose H 2 and are converted into pyrazol derivatives. Thus, the product of the reaction of acrolein on phenylhydrazine gives phenylpyrazol : N = CH.CH=CH 2 N=CH.CH NH.C 6 H 5 1 Glucose, like the aldehydes, reacts in the cold with one molecule of phenyl- hydrazine with liberation of water. On heating with phenylhydrazine, two molecules enter into reaction, and a yellow precipitate is formed. The reaction may be represented by the equation: C 6 H 12 6 + 2NH 2 .NH.C 6 H 5 = C 6 H 10 O 4 (N.NH.C 6 H 5 ) 2 + 2H 2 O+ H 2 . It is interesting to know that, through this compound, dextrose may be con- verted into laevulose; on reduction of the hydrazine derivative, there is formed iso-glucosamine, C 6 H n (NH 2 )O 5 , and this, by treatment with nitrous acid, ia completely converted into laevulose. CON DENS A TIONS. 1 7 7 Among the derivatives of pyrazol is found antipyrine (used as a febrifuge and analgesic), which is obtained by the condensation of ace to-acetic ester with methyl-phenyl-hydra- zine (symmetrical) with liberation of water and alcohol C 2 H 5 .OH. For derivatives of phenylhydrazine, see page 179. (b) Diazo-amido Compounds. On mixing the aqueous or alcoholic solutions of a diazo-salt and an amido compound, there is formed a diazo-amido body: N.C 6 H 5 N.C 6 H 5 1 1 +2C 6 H 5 .NH 2 = 1 1 +C 6 H 5 .NH 2 .HN0 3 . N.O.N0 2 N.NH.C 6 H 5 If the diazo-salt and the primary amine contain different radicals, there are formed diazo-amides which are identical whether R.N:N.C1 reacts on R'NH 2 or R'N:N.C1 on R.NH 2 . But in the case of secondary amines, under the same condi- tions, there will be formed two different isomers. Thus, by the action of diazobenzene chloride, CeHs.NrN.Cl, on mono-ethyl- toluidine, C 6 H 4 (CH 3 )NH.C 2 H5, a body is formed which shows different properties and decomposition products from that formed by the action of diazo-toluene chloride, C 6 H 4 .(CH 3 )N: N.C1, on ethyl-aniline, C 6 H 5 .NH.C 2 H 5 . The formation of diazo-amido derivatives by the action of nitrous acid on amido compounds and their salts must be regarded as the result of two successive reactions: firstly, the formation of a diazo-body, like C 6 H 5 .N :N.OH or its salt; and, secondly, the action of this body on the amine with liberation of water. Thus, the diazo-amido compounds are obtained with the chlorides of the diazo compounds by the action of NaN0 2 on R.NH 2 .HC1 in neutral solution; but in an alkaline solution there is formed only the diazo-amido compound. For example, I 78 ORGANIC SYNTHESES N.C 6 H 5 2C 6 H 5 .NH 2 .HC1 + NaN0 2 + NaOH = 1 1 + 2NaCl + 3H 2 N.NH.C 6 H 5 The diazo-amido compounds are also obtained by the actioa of N 2 3 on a cooled alcoholic solution of the amine; the diazo- amido body, being but slightly soluble, immediately separates out. The ethereal solution of the amine may also be treated with a nitrous ester. In the preparation of the diazo-amido bodies, it is necessary to take into consideration the ease with which they pass into- the isomeric amido-azo compounds. (c) Azo Derivatives. In certain cases, in the reaction of diazo- salts on amido compounds, in place of diazo-amido bodies^ there are directly obtained their isomers, the amido-azo com- pounds. 1 If meta-phenylene-diamine, C 6 H 4 <^ Lc NTT 2 ' * S diazo-benzene nitrate, CeHs.N : N.ON0 2 (action of nitrous acid on aniline nitrate, C 6 H 5 .NH 2 .HN0 3 ), there is formed chrysoidine nitrate : N.C 6 H 5 II N.C 6 H 3 (NH 2 ) 2 HN0 3 . It is not necessary, in the preparation of these bodies, to- separate the diazo-salts; they may be obtained by the action of nitrous acid on a mixture of the amines. Thus, if a cooled alkaline solution of sodium nitrite is gradually added to a mix- ture of the hydrochlorides of aniline and dimethylaniline, there is formed: C 6 H 5 .N:N.C 6 H4.N(CH 3 ) 2 . 1 For the formation of the azo derivatives by direct addition, see p. 155. CON DENS A TIONS. 179 In the same manner, by the action of nitrous acid on meta- phenylene-diamine, triamido-azo-benzene is formed : NH 2 .C 6 H4.N:N.C 6 H 3 (NH 2 ) 2 . It is probable that there is at first formed NH 2 .C 6 H 4 .N:N.OH, which then reacts on another molecule of C 6 H 4 (NH 2 ) 2 . The salts of the diazo compounds react readily with phenols and their derivatives: C 6 H 5 .N :N.N0 3 + C 6 H 5 .OH = C 6 H 5 .N :N.C 6 H 4 .OH + HN0 3 . To prepare hydroxy-azobenzene, a solution of 30 gms. of potassium nitrite in 4 litres of water is added to a solution of 20 gms. of phenol in 2 litres of water. On agitating, there is at first formed a yellow precipitate which becomes red. After standing for 21 hours, the precipitate is dissolved in ammonia in order to separate it from resinous matters. The solution is reprecipitated by the addition of acid, and the compound is finally crystallized from boiling dilute alcohol. In the reactions of diazo-salts on phenols and amines, the N:N group takes the para-position generally with respect to the OH or NH 2 group, and the ortho-position when the para is occupied. The salts of the diazo compounds condense also with metal- lic derivatives, with nitro compounds of the aliphatic series, with esters, and with ke tonic acids like ace to-acetic acid; but in such cases azo derivatives are not obtained, but derivatives of phenyl hydrazine. Thus, with ace to-acetic ester, there is H CO.CH 3 formed the ester of a rather stable acid, , C 6 H 5 N:N = C.CO.OC 2 H 5 which only decomposes at 180 C., giving carbonic acid and CH 3 .CO.CH:N.NH.C 6 H 5 . The azo compounds are obtained' by the oxidation of aro- matic amido compounds, 4H being removed from two molecules i8o ORGANIC SYNTHESES. of the amine. Thus, aniline, oxidized with potassium per- manganate, gives azo-benzene: C 6 H 5 .N C 6 H 5 .N -2H 2 = C 6 H 5 .N II C 6 H 5 .N Other oxidizing agents may also be employed, such as potas- sium ferricyanide in alkalines olution, chromic acid in acetic acid solution, hydrogen peroxide, 1 or even by passing the vapors of the amine over heated lead oxide. The oxidation of the disubstituted hydrazines may be carried out by agitating their aqueous or alcoholic solution with the oxide of mercury or silver, Hg 2 0, or Ag 2 0, or by employing ferric chloride. The disubstituted hydrazines are easily decomposed: NH + 2 = 65 N- N : N.N + 2H 2 0. (d) Azoxy Compounds. The aromatic nitro compounds, by the action of alkaline reducing agents, are converted into azoxy compounds by the removal of three molecules of oxygen from two molecules of the nitro-body: R.Nv 2R.N0 2 + 3H 2 = | >0+3H 2 0. R.N/ The nitro-body is treated with an alcoholic solution of caustic potash (Zinin's process). In some cases, for example with azoxy-benzene, a better result is obtained by using sodium methylate dissolved in methyl alcohol. To prepare the azoxy bodies, it is convenient to employ sodium amalgam, which is 1 Barzilovsky, On the Azo Derivatives of Toluene, Kieff, 1878 (in Russian). CONDENSATIONS. 181 allowed to act on the aqueous or alcoholic solution of the nitro- compound. To avoid the formation of an azo-body, produced by the oxidation of the hydrazo compound which is at first formed, the sodium amalgam is added, a little at a time, and in slight excess only, at a temperature as low as possible. There is always formed a small quantity of azo derivative, which is removed by treating the product with tin chloride, SnCl 2 , and sulphuric acid. Zinc dust, caustic potash, and stannous oxide in alkaline solution, are all good reducing agents, but they react too energetically; they are only employed for the prepara- tion of hydrazo or azo bodies. CHAPTER VIII. TYPES OF SYNTHESES. I. FIXATION OF CARBON MONOXIDE (CO). CARBON monoxide combines with alkalies, and gives salts of formic acid; it also combines with alcoholates to give salts of the homologues of formic acid: CH 3 .CH 2 .ONa + CO = CH 3 .CH 2 .CO.ONa. If, instead of an alcoholate, there is taken its mixture with a salt of an acid, there are obtained acids having an increased number of carbon atoms. Carbon monoxide, at the moment of its formation, combines with phenols and their derivatives, the hydrogen of the CH group passing into the CHO group. Phenol, in this manner, is converted into salicyl aldehyde by the simultaneous action of caustic soda and chloroform : In carrying out this reaction, two to three times the theo- retical amounts of chloroform and caustic soda are taken; the chloroforfn is added drop by drop to the alkaline solution of the phenol slightly heated; by raising the temperature the reaction is finally completed. The liquid is then acidulated; the excess of phenol is distilled off in a current of steam; then the liquid is filtered to remove resinous matters, and the alde- hyde which has been formed is extracted with ether. If it 182 TYPES OF SYNTHESES. 183 distils with steam, it is separated from the phenol by means of sodium bisulphite, NaHSOs. Distillation in steam can also be used in order to separate the isomers which may be formed; ortho-oxy-aldehydes are generally much more volatile than para-isomers. The reaction of phenols with caustic soda and chloroform can be considered as a condensation, with liberation of water, of the phenol with the tri-hydrate which is at first formed: CHC1 3 + 3NaOH = CH (OH) 3 + 3NaCl, + H 2 0. The formation of ketones affords a special case of the fixa- tion of carbon monoxide; for example, the formation of ethyl- ketone, C 2 H 5 .CO.C2H 5 , by the action of carbon monoxide on sodium ethyl, C 2 H 5 .Na. Carbon monoxide, when heated with potassium, gives K 6 C 6 06, a potassium salt of hexa-oxybenzene; the same product is also obtained as a secondary product in the preparation of potassium. With alcohol this compound gives the salt of rhodizonic acid, C 6 (0 2 )(0 2 )(OK) 2 . II. FIXATION OF CARBON DIOXIDE (C0 2 ). The fixation of carbon dioxide by hydrocarbons (for instance, benzene) only takes place in the presence of aluminium chloride : C 6 H 6 +C0 2 =C 6 H 5 .CO.OH. * With sodium compounds, however, the reaction takes place more easily. Thus, CH 3 .CH 2 Na gives the sodium salt of pro- pionic acid; NaC=C.C 6 H 5 is converted into the salt of phenyl- propiolic acid. 1 84 ORGANIC SYNTHESES. The formation of benzoates by the action of carbon dioxide and sodium on brom-benzene, C 6 H 5 Br, is really the fixation of C0 2 by C 6 H 5 Na at the moment of its formation. Sodium acetanilide combines with carbonic acid in the cold: The product which is formed gives an isomer when heated, the anilide of malonic acid being formed : C 6 H 5 N /CO.CH 2 .CO.ONa \H The phenates combine with carbonic acid on heating, and are converted into oxy-acids; phenol gives salicylic acid. There is at first formed the salt of the acid ester of carbonic acid: 'ONa >.C 6 H 5 > which afterwards, on heating to 120-130 C., becomes isom- erized into sodium salicylate : m /ONa p H /OH \O.C 6 H 5 =C6H4 \CO.ONa' The most convenient method of preparing salicylic acid is to add liquid carbonic acid to the absolutely dry phenate enclosed in an autoclave; the mixture is heated for several hours at 120-130 C. By heating sodium salicylate in a current of carbon dioxide to 200 C., there are formed the salts of dicarboxyl and tricar- boxylphenol acids, C 6 H 3 .OH(CO.OH) 2 and C 6 H 2 .OH(CO.OH) 3 . Polyhydric phenols will also combine with carbon dioxide when heated with an aqueous solution of ammonium carbonate. TYPES OF SYNTHESES. 185 The sodium compound of oxy-quinoline, heated with liquid carbon dioxide, is converted entirely into oxy-quinoline car- boxylic acid: C 9 H 6 (ONa)N + C02=C 9 H 5 (OH)(CO.ONa)N. The formation of oxy-acids by treating phenols with carbon tetrachloride, CCU, and caustic soda, can be considered as the fixation of carbon dioxide in the nascent state, or as a con- densation of the tetrahydrate of carbon and phenol with loss of water : C(OH) 3 +H2 > NCOH3 = C 6 H 4co OH +H 2 0. The reaction is brought about by adding carbon tetrachloride and alcohol to a strongly alkaline solution of phenol until completely dissolved; the mixture is then heated in a sealed tube until sodium chloride is no longer formed. The fixation of carbon dioxide can be brought about by the substitution of H by CN, which is then saponified; or the S0 2 .OH group may be replaced by CO.OH. III. CONDENSATION BY THE TRANSFORMATION OF THE CO GROUP INTO C.OH AND C.OX. In the reduction of aldehydes and ketones, two molecules combine with the addition of hydrogen to form dihydric alco- hols; and the CO group is converted into C.OH. Benzalde- hyde behaves in this manner; with zinc and hydrochloric acid in alcoholic solution it gives hydrobenzoin : C 6 H 5 .CH.OH 2C 6 H 5 .COH+H 2 = | C 6 H 5 .CH.OH ORGANIC SYNTHESES. The sodium derivative of this glycol can be obtained by the action of sodium amalgam on benzaldehyde in the absence of water. Some aldehydes of the aliphatic series are converted into dihydric alcohols by the use of alcoholic soda. Thus, isobutyric aldehyde, (CH 3 ) 2 .CH.CHO, gives a glycol simultaneously with isobutyric acid: (CH 3 ) 2 .CH.CH.OH (CH 3 ) 2 .CH.CH.OH The reaction may also be carried out by the condensation of two different aldehydes. Thus, a mixture of ordinary alde- hyde and isobutyric aldehyde with sodium amalgam will give : (CH 3 ) 2 .CH.CH.OH CH 3 .CH.OH' For the formation of the compound, [(C 6 H 5 ) 2 CSH] 2 , see under substitutions. The reduction of the CO group to C.OH does not take place by the action of free hydrogen, but by the hydrogen of another molecule of the same substance. The formation of aldol according to Wurtz, by the action of hydrochloric acid on aldehyde, is a reaction of this kind: CH 3 .CHO + CH 3 .CHO = CH 3 .CH(OH).CH 2 .CHO. Aldol. The formation of aldol may be considered as a condensation of a dihydrate with aldehyde and liberation of water, or as a condensation of chlorhydrin, CH 3 CH(OH)C1, with aldehyde and liberation of hydrochloric acid : 4- HCH 2 .CHO = CH 3 .CH(OH) .CH 2 .CHO + H 2 0. CH 3 .CH(OH)C1 + HCH 2 .CHO = CH 3 .CH(OH) .CH 2 .CHO + HC1. TYPES OF SYNTHESES. 187 A 1 per cent, solution of caustic soda on a solution of ortho- nitrobenzaldehyde in acetone, gives rise to a reaction which may be expressed as follows : _ rH /(l)N0 2 Ul4 \(2) CH(OH).CH 2 .CO.CH 3 . In the aromatic series the condensation of aldehydes takes- place a little differently; that is to say, the CO group of the aldehyde radical is converted into C.OH at the expense of the hydrogen of the other CHO group. It is in this manner that benzaldehyde is converted into benzoin by the action of a dilute alcoholic solution of potassium cyanide : C 6 H 5 .CO C 6 H 5 .CHO+C 6 H 5 .CHO = | C 6 H 5 .CH.OH The conversion of the CO group into C.OH is also brought about by the union of hydrocyanic acid with aldehydes and ke tones : CH 3 .CHO + HCN = This reaction is carried out by leaving the aldehyde in contact with the theoretical quantity of hydrocyanic acid (25 per cent. aqueous solution) at the ordinary temperature, or by slightly heating. The acid reacts more readily in the nascent condition; to obtain this condition, the aldehyde or ketone in ethereal solu- tion is mixed with the theoretical quantity of moist potassium cyanide, after which there is added drop by drop the calculated amount of a concentrated mineral acid. In certain cases, the cyanhydrins of dihydrates 1 which are 1 The anhydrides of the glycols also combine with hydrocyanic acid to form cyanhydrins. Through the intervention of the cyanhydrins it is possible to> / 3 /.v Cell/ +| =C 6 H 4 < >CH 2 +H 2 0; X OH CO.OH X) -- CO/ Intermediate body. CeH^ Q _ QQ /CH 2 H 2 = CeH^ Q QQ "^CH. Coumarin. This reaction is carried out by heating 1 part aldehyde, 1 part dehydrated sodium acetate, and 1J parts acetic anhydride for 8 to 12 hours on an oil-bath at 150-160 C., using an inverted condenser. The product of the reaction is dissolved in a dilute alkaline solution; the unattacked aldehyde is removed by ether. The coumarin is precipitated from its alkaline solution by addition of hydrochloric acid, and is crystallized from benzene. Aldehydes and ketones also condense with dicarboxylic acids. Thus: CH 3 .CHO+CH 2 .(CO.OH) 2 -H 2 = CH 3 .CH:C.(CO.OH) 2 . Ethylidene malonic acid. The reaction is carried out by saturating the cooled mixture of aldehyde and acid with hydrochloric acid gas, or by heating the mixture in a sealed tube with acetic anhydride or glacial acetic acid. Secondary products are obtained; in the above example, 194 ORGANIC SYNTHESES. for instance, some crotonic acid is formed by reason of the splitting-off of carbon dioxide. Succinic acid, in condensing, also gives rise to intermediate compounds of the aldol type, but only in the form of the sodium salt. With benzaldehyde, the salt of the following oxy-acid is formed : C 6 H 5 .CH(OH) .CH.CO.OH CH 2 .CO.OH* This acid, on treatment with acetic acid, immediately decom- poses with the formation of a lactone : CO.OH C 6 H 5 .CH.CH.CH 2 .CO. !_ o I The anhydrides of the dicarboxylic acids (for example r phthalic anhydride) behave in the same manner as aldehydes. Heated with sodium acetate and acetic anhydride, it gives phthalyl-acetic acid, which does not have a symmetrical formula as usually believed; it may be represented by = CH.CO.OH C 6 H 4 < \ xx)/ which, in fact, is a phthalide derivative. The compound obtained by the action of phthalic anhydride on succinic acid, CH 2 .CO.OH CH.CO.OH <. CH 2 .CO.OH /C.OH ' CH 2 .CO:OH 3H < =CeH o \J \J/ I TYPES OF SYNTHESES. 195 is immediately decomposed with loss of water and carbon dioxide to form a double lactone : There also exist other synthetic methods, in which the for- mation of compounds belonging to the aldol type play an important role. The preparation of coumarin, by heating phenol with malic acid, can be explained by admitting the formation of the aldehyde of malonic acid with liberation of formic acid : CO.OH H H.CO.OH CH.OH + OH-H 2 = CHO I I CH 2 .CO.OH CH 2 .CO.OH this aldehyde immediately combines with phenol, and the pro- duct so formed is decomposed into water and coumarin: | -2H 2 = CH 2 .CO. CH(OH) .C 6 H4.0H .OH CH.CO- Benzaldehyde also condenses with benzyl cyanide in the presence of sodium alcoholate : | = C. CHO CH 2 .CN CH = C.CN It is not impossible, in the synthesis of hydrocarbons, by the aid of dehydrating agents, to obtain aromatic aldehydes ORGANIC SYNTHESES. and hydrocarbons with formation of compounds of the aldol type, which further react to give more complicated bodies. The formation of diphenyl-ethane, for example, from aldehyde and benzene may be expressed by the following equations: CH 3 .CH(OH) .C 6 H 5 + C 6 H 6 = CH 3 .CH(C 6 H 5 ) 2 + H 2 0. A solution of aldehyde is heated with a large quantity of concentrated sulphuric acid, and the theoretical quantity of benzene is added; then, after some hours' standing, the hydro- carbon is removed with water. It is better to use the acetals than the aldehydes themselves. Aldehydes also condense with different derivatives of aro- matic hydrocarbons. Thus, if a well-cooled mixture of aldehyde and phenol is added drop by drop to tin chloride, the following reaction takes place : CH 3 .CHO + 2C 6 H 5 .OH = CH 3 .CH(C 6 H4.0H) 2 + H 2 0. Benzaldeyde, heated with aniline hydrochloride in the presence of zinc chloride, condenses as follows : C 6 H 5 .CHO + 2C 6 H 5 .NH 2 .HC1 -C 6 H 5 .CH(C 6 H 4 .NH 2 .HC1) 2 + H 2 0. 1 Phthalic anhydride condenses with phenols in the same manner as aldehydes and ketones in the presence of dehydrat- ing agents: co C /(C 6 H,OH) 2 C 6 H 4 ^ >0 + 2C 6 H 5 .OH=C 6 H4< No +H 2 0. XXX XXX 1 The hypothesis that compounds of the aldol type are at first obtained is confirmed by the fact that benzaldehyde with dimethylaniline, in the presence of a mineral acid, reacts according to the following equation, giving a derivative of benzhydrol: C 6 H 5 .CHO+ C 6 H 5 .N(CH 3 ) 2 = C 6 H 5 .CH(OH).C 6 H 4 .N(CH 3 ) 2 . TYPES OF S YNTHESES. 1 9 7 The reaction, however, may be different; thus, if phenol is added to a heated mixture of phthalic anhydride and sulphuric acid, hydroxy-benzoyl-benzoic acid 1 is formed, which then, by loss of water, forms hydroxy-anthraquinone : /CO X /CO.C 6 H 4 .OH C 6 H 4 < >0 + C 6 H 5 .OH = C 6 H 4 < XJCK XJO.OH /CO.C 6 H4.0H /C(X C 6 H 4 < -H 2 0=C 6 H 4 < >C 6 H 3 .OH. X CO.OH XXX The aromatic compounds also condense (with loss of water) with different alcohols of the aliphatic and aromatic series. Benzene with benzhydrol gives triphenylme thane. 2 The reac- tion only takes place in the presence of dehydrating agents. Usually, a mixture of the reacting bodies with P20 5 , ZnCl 2 , or H 2 S0 4 , is heated. Thus, nitro-benzyl alcohol condenses with benzene by simply shaking with concentrated sulphuric acid r to give: '(1) N0 2 CeH4< \(3) CH 2 .C 6 H 5 In the same manner, by heating to 250-300 C., a mixture of aniline (and its homologues, or their salts) with ordinary alcohol (or its homologues) in the presence of zinc chloride or phosphoric anhydride, there is a condensation with loss of water : C 6 H 5 .NH 2 +C 2 H 5 .OH=C 6 H 4 0+C 6 H 6 =| ' CH 2 .C(X CH 2 .CO.OH 2 Hemilian, On Some Homologues and Isomerides of Triphenylmethane, St. Petersburg, 1886 (in Russian). 198 ORGANIC SYNTHESES. As a secondary product, there is sometimes obtained a secondary base. It is interesting to note the formation of a-naphthylamine (from the condensation of aniline with furfuran) by heating pyromucic acid, aniline, and zinc chloride : X CH = CH /CH=CH C 6 H 5 .NH 2 + | = C 6 H 3 (NH 2 ) | +H 2 0. Furfuran. a-Naphthylamine. Aromatic compounds also condense with various acids. By heating acids or their anhydrides with hydrocarbons in a sealed tube, together with phosphoric anhydride, ketones are produced: C 6 H 6 + C 6 H 5 .CO.OH - H 2 = C 6 H 5 .CO.C 6 H 5 . Phenols react more easily than hydrocarbons; dioxy-aceto- phenone is obtained by heating to 150 C. glacial acetic acid with resorcin and zinc chloride : -f CH 3 .CO.OH=CH 3 .CO.C 6 H 3 /^ By heating aniline with acetic anhydride and zinc chloride, the acetyl group enters the benzene nucleus and also the NH 2 group, and there is formed the compound, CHs.CO.CeH^NH. CO.CH 3 , which, on saponification with acids, gives amido-ace- tophenone, CH 3 .CO.C 6 H 4 .NH 2 . /OTT The ammonia-aldehydes, R.CH<^ -^-^ , readily condense with different compounds with elimination of water. With a concentrated aqueous solution of hydrocyanic acid, they form /CN aceto-acetic ester they give hydropyridine derivatives: thus, aldehyde-ammonia with aceto-acetic ester gives the ester of hydrocollidine-dicarboxylic acid : 1 1 N. Liubavine, The Pyridine Compounds, Moscow, 1887 (in Russian). nitriles of the a-amido-carboxylic acids, R.CH<^ TTT With TYPES OF SYNTHESES. 199 CO.CH 3 XOTT 2 1 +CH 3 .CH< vn _ 3 H 2 CH 2 .CO.O.C 2 H 5 =C 5 H 2 N(CH3)3(CO.O.C 2 H 5 ) 2 . The formation of the ester of aceto-acetic acid and its ana- logues can also be considered as a condensation with elimina- tion of water : CH 3 .CO.OH+CH3.CO.OH-H 2 0=CH 3 .CO.CH 2 .CO.OH. This condensation is produced, with elimination of alcohol, by the action of sodium on ethyl acetate. The other esters behave in a similar manner. Two different acids may also be condensed; this is brought about by treating a mixture of the two esters with sodium or sodium alcoholate. For example, by using an ethereal solution of ethyl oxalate and acetate, there is obtained, by the action of sodium ethylate, C 2 H 5 ,ONa, a sodium salt of aceto-oxalic ester : CO.OC 2 H 5 + CH 3 .CO.OC 2 H 5 + C 2 H 5 .ONa O.OC 2 H 5 v/ i CO.OC 2 H 5 | +2C 2 H 5 .OH. CO.CH(Na).CO.OC 2 H 5 With a mixture of ethyl oxalate and succinate, there is formed an ester of succinyl-oxalic acid, a tribasic acid : CO.OC 2 H 5 CH 2 .CO.OC 2 H 5 + I +C 2 H 5 .ONa = io CO.OC 2 H 5 CH 2 .CO.OC 2 H 5 | | +2C 2 H 5 .OH. C(Na).CO.OC 2 H 5 200 ORGANIC SYNTHESES. In the aromatic series, benzoyl-benzoic acid offers a case analogous to that of aceto-acetic acid. The hydroxy-benzoic acids also condense directly by the action of sulphuric acid; only, in the case of ketonic acids, there are formed closed-chain compounds, such as the hydroxy-anthraquinones. The condensation of acids of the aromatic series with those of the aliphatic series can be brought about by means of the diazo-bodies. The ester of diazo-acetic acid, on heating with benzaldehyde and toluene, gives nitrogen, N 2 , and the ester of benzoyl-acetic acid: N x 1 1 >CH.CO.OH + C 6 H 5 .CHO = C 6 H 5 .CO.CH 2 .CO.OH + N 2 . W V. CONDENSATION WITH LOSS OF HALOGEN ACID, OF A METALLOID, OR OF A SALT. The halogen compounds of the aliphatic series, and those of the aromatic series containing a halogen atom in the side- chain, react with hydrocarbons, with liberation of a halogen acid: HI=C n H 2n+ i The reaction is brought about by heating the hydrocarbon and halide with oxides of zinc, magnesium, and calcium. The aromatic hydrocarbons readily combine with halogen deriva- tives in the presence of zinc dust, or, better, in the presence of aluminium chloride or bromide : l C 6 H 6 + 2CH 3 C1 - 2HC1 = C 6 H 4 (CH 3 ) 2 . This reaction takes place with such regularity that different isomers can be obtained at will. With aluminium chloride the principal derivatives are meta, with zinc dust para and ortho. If the halogen compound is gaseous, like methyl chloride, it is passed into the heated hydrocarbon to which aluminium 1 The chlorides of iron and zinc act in the same manner. TYPES OF SYNTHESES. 201 chloride has been added; if it is liquid, it is mixed with the hydro- carbon, and the metallic chloride is added little by little until the halogen acid is no longer liberated. When the reaction is finished, the product is washed with water and then fractionated, for there is always obtained a mixture of several hydrocarbons. Thus, benzene, treated with methyl chloride besides methyl-benzene, C 6 H 5 .CH 3 , also gives, a whole series of methyl-benzenes up to the hexa compound,. C6(CH 3 )6, inclusively. This process is never complete, as by the action of the aluminium chloride a reverse reaction earn take place: C 6 H 5 .CH 3 + HC1 - C 6 H 6 + CH 3 C1. Zinc chloride acts much more slowly than aluminium chlor- ide; nevertheless, in certain cases, it is preferable (for example, with naphthalene and benzyl chloride, CeHs.CH^.Cl), for then less secondary products are obtained. Metallic zinc only reacts by being converted into zinc chloride at the expense of the chlorine compound. In place of chlorine derivatives, the bromine or iodine compounds may also be used. With the latter it is necessary to heat in a sealed tube with a small quantity of iodine. Normal propyl bromide, CH 3 .CH 2 .CH 2 .Br, on condensing with benzene under the influence of aluminium bromide, gives isopropyl-benzene, (CH 3 ) 2 .CH.C6H 5 , for by the action of alumin- ium bromide alone this same bromide is converted into isopropyl bromide. Allyl chloride, CH 2 :CH.CH 2 .C1, with benzene and aluminium chloride, does not give allyl-benzene, but diphenyl- propane (C 6 H5) 2 .C 3 H 6 . 1 1 There is consequently a substitution of chlorine by C 6 H 5 and a fixation of C 6 H 6 . An analogous case presents itself in the action of ethylene on benzene in the presence of aluminium chloride, this even being a good method for the preparation of ethyl benzene: C 2 H 4 +C 6 H 6 =C 6 H 5 .C 2 H 5 . This reaction may be explained by admitting that the C 3 H 4 is first converted into C 2 H 5 C1, which then reacts with C 6 H 6 . According to Friedel and Crafts, in syntheses with the aid of aluminium chlo- 202 ORGANIC SYNTHESES. Aromatic acids containing a halogen in the side-chain also condense with the aromatic hydrocarbons in the presence of the halogen salts of aluminium : C 6 H 5 .CH. (Br.)CO.OH + C 6 H 6 = HBr + (C 6 H 5 ) 2 .CH.CO.OH. Bodies containing several halogen atoms behave in the same manner with hydrocarbons in the presence of aluminium chloride as monohalogen derivatives. Chloroform with Al 2 Cl6 reacts with 3C 6 H 6 to give triphenylme thane, CH(C 6 H 5 ) 3 . This process, in fact, is used for the preparation of the latter body; as a secondary product, diphenylme thane, CH 2 (Cells) 2 , is formed. With carbon tetrachloride and benzene, in the presence of aluminium chloride, C1 4 is not replaced by (C 6 H 5 ) 4 , as would at first be thought; only 3C1 are replaced, and CC1(C 6 H 5 ) 3 , triphenyl-chlor-methane, is formed. Acetylene tetrabromide with benzene and aluminium chloride gives anthracene anji a small quantity of triphenyle thane and brom-benzene : l CH.Br 2 | +2C 6 H 6 =4HBr+C 6 H 4 CH.Br 2 ride there is formed an organo- metallic compound (which they have not been able to isolate, however) between A1 2 C1 6 and the benzene (or other hydrocarbon), with liberation of hydrochloric acid: C 6 H 5 . A1 2 C1 5 = A1 2 C1 6 + C 6 H 6 -HCL. This compound then reacts with halogen derivatives, regenerating A1 2 C1 6 . Accord- ing to Gustavsonn, however, by the action of A1 2 C1 6 on aromatic hydrocarbons, condensation products are formed, as, for example, A1 2 C1 6 .6C 6 H 6 . During their formation there would be considerable heat liberated which would account for their strongly increased reactivity. 1 An interesting formation of derivatives of triphenylethane is in the con- densation of phenols with the dichlor-esters. If the phenol is intimately mixed with the dichlor-ester, the mixture heats up, a brisk reaction takes place, with liberation of hydrochloric acid and ethyl chloride. With an excess of phenol a reddish-colored resinous substance is obtained soluble in alkalies. The re- action may be thus expressed: CH 2 .C1 CH 2 .C 6 H..OH I + 3C.H,.OH=| +2HC1+C 2 H 5 OH. CHC1.0C 2 H 5 CH(C 6 H 4 OH) 2 Dichlor-ester. Phenol. Trihydroxy- triphenylethane. TYPES OF SYNTHESES. 203 Phenols, in the presence of zinc dust or zinc chloride, react like hydrocarbons with the halogen compounds : C 6 H 5 .CH 2 C1 + C 6 H 5 .OH = C 6 H 5 .CH 2 .C 6 H 4 .OH + HCL Phenol with carbon tetrachloride and a small quantity of zinc chloride gives aurine : CC1 4 + 3C 6 H 5 .OH = (C 6 H 4 .OH) 2 C/ 1 +4HC1. X The halogen compounds condense very readily with tertiary amines : This reaction is carried out on a water-bath without any con- densing agent. The acid chlorides of both the aliphatic and aromatic series condense with hydrocarbons (in the presence of aluminium and zinc chlorides) to form ke tones : f C 6 H 5 .CO.C1 + CioH 8 = C 6 H 5 .CO.Ci H 7 + HCL Two molecules of the acid chloride and one molecule of the hydrocarbon may also take part in the reaction : 2C 6 H 5 .CO.C1 + C 6 H 2 (CH 3 ) 4 - C 6 (CH 3 ) 4 ' + 2HC1. Chlorides of dicarboxylic acids react with either one or two molecules of the hydrocarbon; thus, the chloride of isophthalic acid with one molecule of benzene gives : (1) CO.C 6 H 5 . (3) CO.C1 ' 204 ORGANIC SYNTHESES. while with two it gives isophthalophenone: (l)CO.C 6 H 5 Phthalyl chloride with benzene, in the presence of aluminium chloride, gives phthalophenone : C (C 6 H 5 ) 2 The preparation of the above ketones is carried out by gradu- ally adding aluminium chloride to a mixture of the acid chloride and the hydrocarbon until there is no further liberation of hydrochloric acid. Carbonyl chloride, in the presence of aluminium chloride, reacts with hydrocarbons in the same manner -as the acid chlor- ides. With benzene it gives benzoyl chloride : CO.C1 2 + C 6 H 6 = C 6 H 5 .CO.C1 + HC1. But, as benzoyl chloride reacts in turn on benzene, the final product is benzophenone : C 6 H 5 .CO.C 6 H 5 . Dimethyl-aniline, at 50 C., reacts with carbonyl chloride to give dimethyl-amido-benzoic acid, or, rather, its chloride : The chlorine derivatives of the substituted carbamic acids, Cl.CO.NHR, with the aromatic hydrocarbons, (for example, tolu- ene, C 6 H 5 .CH 3 ) give the substituted amides of the aromatic acids : /(l)CH co NHR This is one of the methods of synthesizing the aromatic acids. TYPES OF SYNTHESES. 205 Cyanogen chloride, in the presence of aluminium chloride, reacts with benzene to give benzo-nitrile, CeH 5 .CN. The reaction of the aliphatic acid chlorides with aluminium chloride is of interest. 1 Thus, acetyl chloride, diluted with chloroform, reacts with aluminium chloride at 40-45 C., lib- erating a large amount of hydrochloric acid gas, and forming a white crystalline substance having a composition of Ci2Hi4 6 A1 2 C1 8 , the formation of which may be expressed by the equation : 6(C 2 H 3 OC1) + A1 2 C1 6 = 4HC1 + C 21 H 14 6 A1 2 C1 8 . This organo-metallic compound is decomposed with alcohol into diace to-acetic acid ester: Benzyl cyanide, C 6 H 5 .CH 2 .CN, easily replaces the hydrogen in the CH 2 group in the presence of halogen compounds. Thus, by the action of benzyl chloride, C 6 H 5 .CH 2 C1, and sodium alco- holate, with benzyl cyanide, there. is obtained the compound: By gently heating a mixture of benzyl cyanide, sodium, and methyl iodide, there is produced the nitrile of hydro-atropic acid: The metallic cyanides (KCN, NaCN, ferrocyanides, etc.) react with the halogen compounds of the aliphatic series and with alkyl acid sulphates, forming nitriles. The reaction is ordinarily brought about by a prolonged boiling of the solution of halogen 1 See Jour. Soc. Phys. Chim. Russe, vol. 20, p. 81. 206 ORGANIC SYNTHESES. compound and cyanide in dilute alcohol. The nitriles are isolated and purified by distillation; often they are not isolated, but by saponification are converted directly into carboxylic acids. The tertiary halogen compounds react with difficulty with the alkaline cyanides; the latter are replaced by the double cyanide of mercury and potassium, Hg(CN)2.2KCN. Aromatic compounds containing a halogen in the side- chain also react with metallic cyanides : C 6 H 5 .CH 2 C1 + KCN = C 6 H 5 .CH 2 .CN + KC1. If dilute alcohol is used as a solvent, the amide of phenylacetic acid, CeH5.CH2.CO.NH2 is obtained as a secondary product. To convert the chloride of triphenyl-carbinol, (C 6 H 5 ) 3 .CC1, into the nitrile, it is heated with mercury cyanide, Hg(CN)2, to 150- 170 C. Halogens in the aromatic nucleus are replaced by CN only with difficulty, and never completely, even at 300-400 C.; by using potassium ferrocyanide, the reaction takes place very incompletely. The iodine compounds react somewhat more readily, than the other halogen derivatives. Brom-benzyl bromide, CeH Q- -g r , on boiling with potassium cyanide, is converted into brom-benzyl cyanide, Phenyl-brom-acetic acid, on boiling with potassium cyanide, loses its bromine and is converted into diphenyl-succinic acid : 2C 6 H 5 .CHBr.CO.OH +2KCN = 2KBr + (CN) 2 + C 6 H 5 .CH.CO.OH I C 6 H 5 .CH.CO.OH In the aromatic series, the nitriles are generally obtained through the intervention of the sulphonic acid derivatives by heating the latter with pure potassium cyanide, or with potas- TYPES OF SYNTHESES. 207 slum ferrocyanide. If necessary, the reaction may be carried out in an atmosphere of carbon dioxide. The nitrile is isolated by distillation: These bodies may also be obtained by replacing NH 2 with CN with the aid of the azo compounds. Benzonitrile, for ex- ample, is obtained by slowly adding with agitation the solution of the diazo chloride, heated to 90 C., to the double cyanide of copper and potassium. This double cyanide is prepared by adding 25 gms. of a 96 per cent, solution of potassium cyanide to a boiling solution of 25 gms. of copper sulphate in 150 cc. of water. The acid chlorides and bromides also react, on heating, with metallic cyanides : * CH 3 .CO.C1 + Ag.CN = CH 3 .CO.CN + AgCl. Although the alkaline cyanides, potassium ferrocyanide r and the double cyanide of mercury and potassium, and some others, with the halogen compounds, give principally nitriles, other cyanides, such as those of silver and zinc and other analo- gous ones, form principally isonitriles or carbylamines. The reaction is carried out at 100 C.: CH 3 I + AgCN =CH 3 NC + Agl. To obtain the carbylamines, for each molecule of iodide there are taken two molecules of silver cyanide, one of which serves for the formation of a double compound with the iso- nitrile, which is subsequently decomposed with water and potassium cyanide. The carbylamine is purified by distillation. 1 For the preparation of the nitriles, see page 117; for the substitution of OH by CN, see page 198; for the combination with HCN, see page 187; and for the action of CNC1, see page 205. -2o8 ORGANIC SYNTHESES. With isopropyl iodide, (CH 3 ) 2 CHI, and silver cyanide, besides the carbylamine, (CH 3 ) 2 CH.NC, there are also formed, as second- ary products, propylene and hydrocyanic acid. The carbylamines are easily obtained by the energetic reac- tion of alcoholic potash on a mixture of chloroform and a salt of an amine l : CHC1 3 + NH 2 .CH 3 + 3KOH = CH 3 .NCN + 3KC1 + 3H 2 0. Jt is on this formation of carbylamine that is based the charac- teristic reaction for chloroform. Compounds which contain the groups, CO.CH 2 .CO or CO.CHR.CO, can have the hydrogen of these groups easily replaced by sodium, and these sodium derivatives which are formed exchange the metal for an R group by the action of the halogen compound of the aliphatic series, and, in certain cases, of the aromatic series. Ace to-acetic ester, malonic ester, and others can have one or two atoms of hydrogen replaced by a radical. The manner of procedure is the following: A calculated quantity of sodium in the least possible amount of absolute alcohol is added to the ester, and afterwards, with cooling if necessary, the theoretical quantity of the halogen compound; finally, the reaction is finished, if required, by heating in a flask with a return condenser until the liquor is no longer alkaline. The alcohol is distilled off, and the product is washed with water to remove any halogen salt, and the ester is finally puri- fied by distillation. If an acid chloride is allowed to act on the sodium compound, it is necessary to operate in an ethereal solution. For the preparation of diaceto-acetic ester, as much sodium as possible is dissolved, and there is added little by little an ethereal solution of acetyl chloride, taking a quantity cor- responding to the sodium dissolved. To obtain compounds containing two radicals, it is not CH V 1 Alexeyeff gives the formula of the isonitrile as I >N. CH/ TYPES OF SYNTHESES. 209 always necessary to isolate the first body containing a single radical. After adding for each molecule of alcoholate a cal- culated amount of the halogen compound, and when it is no longer alkaline, a second molecule of alcoholate may be added, followed by the addition of the halogen body. This reaction is of great importance in syntheses, and is applied in a large number of cases. Dike tones which contain CO.CH 2 .CO, and compounds which have S0 2 .CH 2 .CO, behave like ace to-acetic ester towards the alcoholates and the halogen compounds. Condensation, with the production of metallic halogen derivatives, takes place by the action of the organo-metallic compounds on halogen compounds: CHBr CH.C 2 H 5 2 1 1 + (C 2 H 6 ) 2 Zn = 2 1 1 + ZnBr 2 . CH 2 CH 2 C 6 H 5 .CH.C1 2 + Zn(CH 3 ) 2 = C 6 H 5 .CH(CH 3 ) 2 + ZnCl 2 . The reaction is so energetic that it is necessary to moderate it by dilution with ether, benzene, etc. Dichlor-ethyl-ether with zinc-ethyl only replaces one atom of chlorine and forms : CH 2 .C1 .OC 2 H5 Amp to replace the second, it is necessary to heat in a sealed tube. The acid chlorides react very readily with the organo- metallic compounds to form ketones, a result obtained by the further action of the acid chloride on the first product of the direct action. The reaction may be expressed by the following equation : 2CH 3 .CO.C1 + Zn(CH 3 ) 2 = 2CH 3 .CO.CH 3 + ZnCl 2 . 210 ORGANIC SYNTHESES. It is necessary, after the reaction is finished, to treat the product with water or a dilute acid, especially when there is an excess of ZnR 2 ; otherwise it would form tertiary alcohols. When the substances are mixed together, they should be cooled. The iodine compounds, when treated with sodium, nearly all behave according to the following equation : RI+R'I+Na 2 = R.R' Usually the reaction takes place less readily with chlorine and bromine compounds. In certain cases, by employing a mixture of halogen com- pounds, the reaction takes place separately on each one; this is particularly true when the bodies are not attacked with the same energy. Thus, on heating a mixture of octyl bromide and ethyl iodide with sodium, the latter is converted entirely into butane before the temperature becomes sufficiently elevated to attack the octyl bromide; also the latter is converted entirely Bodies containing several halogen atoms behave in the same manner as those which only contain one : +2CH 3 .CH 2 .CH 2 .Br +2Na 2 = In general, the sodium is allowed to act on the mixture of the well-dried halogen compounds, and without alcohol. The mixture is cooled, if necessary, or, on the other hand, heated under a certain pressure. With secondary iodides there may be formed unsaturated hydrocarbons, but it is easy to separate these by shaking with sulphuric acid. In the aliphatic series, the synthesis of the carboxylic acids and their esters is carried out in the same manner. Sometimes the sodium is replaced with silver obtained by the action of zinc TYPES OF SYNTHESES. 211 on silver chloride. Valerianic acid is obtained in this manner by heating /3-iodo-propionic acid and ethyl iodide with silver at 150-180 C.: /?-Iodo-propionic acid alone with silver gives adipic acid. With silver and (CeHs^CCl^ we have the reaction: C(C 6 H 5 ) 2 2(C 6 H 5 ) 2 C.Cl2+2Ag 2 = || +4AgCl. C(C 6 H 5 ) 2 The silver may be replaced by other metals. Thus the reaction, C 6 H 5 Br +CH 2 CLCO.OC 2 H 5 - (Br +C1) =C 6 H 5 .CH 2 .CO.OC 2 H 5 , occurs on heating with copper at 200 C. Brombenzene reacts with ethyl chlor-formate, C1CO.OC 2 H 5 , on heating with sodium amalgam of 1 per cent. Condensations with removal of halogen may also take place with the aid of alkaline cyanides (see page 206) . Condensation with elimination of a halogen acid takes place in certain cases through the action of an alcoholic solution of sodium. Thus, para-nitro-benzyl chloride gives dinitro-stilbene : (4) N0 2 HC.C 6 H 4 .N0 2 1) CH 2 C1 HC.C 6 H 4 .N0 2 As an example of a condensation with elimination of a salt, may be given the formation of ketones by the distillation of certain salts; thus, ordinary acetone is obtained according to the following equation : MO \ro+ CH3 \co - MO \ro+ CH3 \x> CH 3 / + MO/ C MO/ + CH 3 / U ' 212 ORGANIC SYNTHESES. and benzophenone, in the same way, may be prepared from benzoates : C 6 H 5 .CO.OM + MO.CO.C 6 H 5 = CO/9 + The synthesis of the aromatic carboxylic acids, by the fusion of a mixture of an aromatic sulphonic acid and a for- mate, is also a condensation with elimination of a salt : C 6 H 5 .S0 3 M + HCO.OM = C 6 H 5 (CO.OM) + HMS0 3 . VI. CONDENSATION WITH LIBERATION OF HYDROGEN. The reaction expressed by the general equation, R.H + R.H + = R.R + H 2 0, often occurs in the aromatic series. Benzene, for example, among other products, gives diphenyl when its vapors are passed through an iron tube heated to redness and filled with pumice-stone. The formation of diphenyl will explain the production of a certain quantity of benzoic acid in the oxida- tion of benzene with manganese dioxide and sulphuric acid. Naphthalene, by the same reaction as above, gives CioH 7 .CioH 7 . Dimethyl-aniline, dissolved in sulphuric acid and oxidized with lead oxide, is converted into tetramethyl-benzidine : C 6 H 4 .N(CH 3 )2 6 H4.N(CH 3 ) 2 ' v_ A Phenol, on oxidation with potassium permanganate, gives symmetrical diphenol: C 6 H 4 .OH C 6 H 4 .OH' TYPES OF SYNTHESES. 215 Resorcin and hydroquinone, fused with alkalies, are con- verted into : C 6 H 3 (OH) 2 6 H 3 (OH) 2 ' The other phenols, oxy-aldehydes, and oxy-acids of the aromatic series behave in a similar manner. Vanillin, with a hot solution of ferric chloride, gives divanillin : 1 [C 6 H 2 (COH)(OCH 3 )OH] 2 . An aqueous solution of vanillin gives a bluish-violet colora- tion with ferric chloride; if heated, the divanillin is deposited in the form of a white crystalline substance, difficultly soluble in the ordinary solvents, but readily so in alkalies. Gallic acid, oxidized with silver oxide or arsenic acid, gives- the acid: C 6 H(OH) 3 CO.OH C 6 H(OH) 3 CO.OH* In certain cases, hydrogen may be removed indirectly. Thus, iodine, acting on the sodium compound of bodies con- taining the group, CO.CH 2 .CO, splits off sodium, and there is- formed a condensation: CH 3 .CO.CHNa CH 3 .CO.CH.CO.OC 2 H 5 2 +I 2 = | +2NaI. CO.OC 2 H 5 CH 3 .CO.CH.CO.OC 2 H 5 This reaction takes place by dissolving the sodium com- pound in ether and adding the theoretical quantity of a con- centrated solution of iodine in ether. A Dianine, Conversion of Phenols into Diphenols by Oxidation, St. Petersburg, 1880 (m Russian). 214 ORGANIC SYNTHESES. VII. CONDENSATION WITH LIBERATION OF WATER AND HYDROGEN. This reaction takes place in the important synthesis of Skraup, the formation of quinoline and its derivatives by heat- ing various amido compounds with glycerol and sulphuric acid. 1 Quinoline is obtained in the dry distillation of the condensa- tion product of acrolein with aniline : N = CH C 6 H 5 .N:CH.CH.CH 2 (?) -> C 6 H 4 and it is known that sulphuric acid acting on glycerol will give acrolein. In the reaction of Skraup, the removal of hydrogen can be admitted in the product of condensation (with loss of water) of acrolein with amido compounds. The hydrogen which is so liberated may act as a reducing agent; hence there is added to the mixture an oxidizing agent such as nitrobenzene, or, better, sodium nitrophenate. The general method of obtain- ing the quinolines consists in heating for several hours, with a reflux condenser, the amido compounds with glycerol and sul- phuric acid, with some nitrobenzene. The latter is removed by distillation in steam; the remaining liquor is made alkaline, and the free base is removed either by distillation in steam or by ether. Nearly all aromatic compounds give quinoline deriva- tives if they contain an unre placed hydrogen in the ortho position with reference to the amido group. VIII. CONDENSATION WITH LIBERATION OF C0 2 . The formation of ketones (see page 211) falls under this class of condensations, as well as many other cases. Sulphuric acid acting on malic acid gives cumalic acid : 2C 4 H 6 5 - 2H 2 - 2H 2 - 2C0 2 = C 6 H 4 4 = C 5 H 3 2 .CO.OH. The cumalic acid may be considered as a condensation product of malonic aldehyde. 1 See the Mpnograph of Liubavine cited on p. 198. TYPES OF SYNTHESES 215 Tartaric acid, on dry distillation, or by the action of hydro- chloric acid at 180 C., gives pyrotartaric acid: 2C 4 H 6 6 = C 5 H 8 4 + 3C0 2 + 2H 2 0. Oxalic acid, reduced with sodium amalgam, gives desoxalic acid: HO.C(CO.OH) 2 3C 2 H 2 04-C02-02=C 5 H 6 OH= | HO.CH.CO.OH The electrolysis of aliphatic acids is effected with the lib- eration of carbonic acid and hydrogen with a condensation of the hydrocarbon groups which form a part of the acid radical. The electrolysis of the salts of valeric acid gives octane. IX. POLYMERIZATION. Sometimes polymerization is the result of an indirect com- plication of the molecule; in other cases it is the result of a series of consecutive reactions; while, in others still, it is the result of direct condensation. The latter case takes place most often by the action of high temperatures on unsaturated bodies: acetylene gives benzene; valerylene and isoprene give the ter- pene, CioHie; the terpenes themselves are converted into C 20 H 32 , etc. Styrol is converted into its polymeride, metastyrol. Certain bodies bring about polymerization by their simple presence. Terpenes polymerize under the influence of boron fluoride, antimony trichloride, etc. The polymerization of cyanic acid into cyanuric acid l is the result of an indirect condensation, the nitrogen binding the groups together. The structure of cyanuric acid is : C.OH N/\N HO.CV/C.OH N 1 The action of triethyl phosphine, P(C 2 H 5 ) 3 , on phenylcyanate, CN.OC 6 H , is interesting; a minute quantity of the former is sufficient to convert a very large quantity of the latter into cyanuric ester, C 3 N 3 (OC 6 H 6 ) 3 , 216 ORGANIC SYNTHESES. An analogous formula is admitted for cyanphenine, the polymer of benzonitrile, (C 6 H 5 .CN) 3 , which is formed not only by the action of sodium on benzonitrile, but also by the action of sodium on the ethereal solution of a mixture of C 3 N 3 C1 3 and brombenzene : 3C 6 H 5 Br +C 3 N 3 C1 3 +3Na 2 = (C 6 H 5 ) 3 C 3 N3 -f-NaCl +3NaBr. An entirely different case is presented in the polymeriza- tion of nitriles of the aliphatic series by the action of metallic sodium; there is here a direct condensation. The polymerized nitriles are found to be related to the pyrimidine derivatives, 1 which are obtained by the condensation of amidines with aceto- acetic ester. Cyanethine, for example, very probably has the formula : N-C.C 2 H 5 / \ C 2 Ii5.C C.CH 3 . N = C.NH 2 There has also been obtained a double nitrile, C 6 Hi N 2r intermediate between propionitrile and cyane thine. 1 1. Ponomareff, On the Constitution of Cyariuric Acid, Odessa, 1885 (in Russian)* CHAPTER IX. ISOMERIZATION. IT sometimes happens that a body is converted into an isomeric form possessing the same percentage composition, either by the same reaction which gives rise to the first body, or to some other reaction. This displacement of the atoms combined in a molecule can be explained either by the fact of successive reactions, or by the existence of a more stable form to which all the other isomers tend to transform themselves. 1 This latter supposition has been used in order to explain the tendency possessed by various hydrocarbons to pass into their isomers having a symmetrical structure. For example, the butylenes tend to pass into CH 3 .CH:CH.CH 3 . But this fact, as well as the transformation of propyl bro- mide, CH 3 .CH 2 .CH 2 Br, into isopropyl, (CH 3 ) 2 CHBr, by the action of aluminium bromide, the formation of secondary 1 A. Eltekoff, Molecular Transpositions among the Hydrocarbons of the Ethylene Series and among the Saturated Alcohols, Karkoff, 1884 (in Russian). See also the theses of Gustavsonn and Ponomareff, cited on pp. 75 and 216. In some cases, the presence of certain groups in the molecule may be the cause of its isomerization. Vidmann and Fileti have shown the existence of certain rules in this respect. In the benzene derivatives, if the group CH 2 .CH 2 .CH 3 is found in the para position with reference to a CII 3 group, the oxidation of the latter group (conversion into CH 2 OH, CHO, or CO. OH) is accompanied by the transposition of the CH^CH^CHg group into CH(CH 3 ) 2 . Inversely, the reduction of the groups CH 2 OH, CHO, or CO. OH to CH 3 con- verts CH(CH 3 ), into CH 2 .CH 2 .CH3. 217 218 ORGANIC SYNTHESES. butyl alcohol in place of the normal, and the tertiary in place of isobutyl alcohol, can be explained more readily by successive fixations and removals of groups. The isomerization of acetylene hydrocarbons, when they are heated with alkalies in alcoholic solution, really takes place, as shown by Favorsky, 1 by the fixation and then the removal of the alcoholate. Thus ethyl acetylene, CH 3 .CH 2 .C = CH, heated to 170 C. with an alcoholic solution of caustic potash, gives dimethyl acetylene, CH 3 .C = C.CH 3 . In this same manner the different cases of isomerism above noted may be explained. Durol, or tetramethyl-benzene (symmetrical), C 6 H2(CH 3 )4, by the action of sulphuric acid, is converted into adjacent tetra- methyl-benzene. There is in this case an instance of successive reactions, for at the same time there are formed sulphonic acids of the two hydrocarbons and of trimethyl-benzene, and, still further, hexamethyl-benzene. When brom-tribrom-phenol, C 6 H 2 Br 3 .OBr, is heated to 180 C. with concentrated sul- phuric acid, it is converted into the isomer, tetrabrom-phenol, C 6 HBr 4 .OH. The compounds, CnH 2 nBr 2 , heated with water and lead oxide, yield glycols or oxides at the same time as aldehydes and ke tones. In certain cases this may be explained by the fixation of water to the acetylene products which are at first formed. In this manner ethylene bromide is converted into aldehyde. The conversion of the bromide of trimethyl-ethylene (CH 3 ) 2 .CBr (CH 3 ) 2 .CH into the ketone CH 3 .CHBr CH 3 .CO can also be explained by the fixation of water to the unsat- urated alcohol, (CH 3 ) 2 .C II , CH 3 .C.OH 1 See Jour. Soc. Phys. Chim. Kusse, vol. 19, pp. 414 and 553; vol. 20, p. 518. ISOMERIZATION. 219 which is at first formed, and the subsequent splitting-off of water. But the same explanation cannot be used in the case of the transformation of the bromide of di-isopropyl, (CH 3 ) 2 .CBr (CH 3 ) 3 .C | , into the ketone | . (CH 3 ) 2 .CBr CH 3 .CO v The conversion of phenyl-ethylene oxide, V) into CH 2 / phenyl-acetaldehyde, C 6 H 5 .CH2.CHO, by boiling with a 20 per cent, solution, of sulphuric acid, or by the action of acetyl chloride or benzoyl chloride, is also a fixation and removal of water. In the same manner, symmetrical diphenyl-ethylene oxide, , with dilute sulphuric acid at 200 C., is converted C 6 H 5 .CH into diphenyl-acetaldehyde, (C 6 H 5 ) 2 CH.CHO. (C 6 H 5 ) 2 .C X oxBenzene pinacoline, | \0, is converted into the /? (CflH fi ) 2 .C/ compound, (C 6 H 5 ) 3 C.CO.C 6 H5, when it is heated to 150 C. with hydrochloric or hydrobromic acids. 1 Compounds containing nitrogen often give rise to cases of isomerization. When ammonium cyanate is heated it gives urea; 2 the substituted ureas and the thio-ureas may be obtained 1 A. Zagumenny, On the Aromatic Pinacones and Pinacolines, St. Petersburg, 1881 (in Russian). 2 The synthesis of urea can be regarded as the dissociatibn of ammonium cyanate into cyanic acid, CO:NH, and ammonia, which then recombine in a different manner: CO : NH+ NH 3 = CO^** 2 * \1N ii, Inversely, urea, heated in a sealed tube with alcoholic potash, gives cyanic acid and ammonia. 220 ORGANIC SYNTHESES. in the same manner. The esters of true cyanic acid heated to 200-210 C. are converted into the isocyanic esters. The phenylhydrazines,- on heating, give pyrazolines: CH.CH i CIi2 CH.CH2.CH2 II = II I NHNH.C 6 H 5 N - N.C 6 H 5 The isonitriles, on prolonged heating, are changed into nitriles. Thus, heated to 200 C., is converted into C 6 H 5 .CN. The aromatic ketoximes, by the action of various agents, yield isomeric anilides. The oxime derivative of benzophenone, {C 6 H 5 )2C:N.OH, dissolved in acetic acid, by the action of gaseous hydrochloric acid at the ordinary temperatures, is con- verted into benzanilide, CeHs.CO.NH.CeHs. Azoxy compounds are converted into oxy-azo derivatives by sulphuric acid: C 6 H 5 .N X C 6 H 5 .N l> = || . C 6 H 5 .N/ HO.C 6 H4.N The isomerization in this case can be considered as the result of the reaction between the hydrate of diazobenzene, CeHsN'.N.OH, or, more exactly, its sulphate, and phenol formed by the decomposition of the azoxy-benzene by the sul- phuric acid. The diazo-amido compounds, for example, C 6 H 5 .N:N.NH.C 6 H 5 , yCII 1 The formula for this body as given by Alexeyeff is C 6 H 4 <^ | j . ISOMERIZA TION. 221 are converted into amido-azo derivatives, C 6 H 5 .N:N.C 6 H 4 .NH 2 , by a prolonged cooling of their solutions, but more readily by the action of aniline hydrochloride : C 6 H 5 .N : N.NH.C 6 H5+C 6 H 5 .NH 2 .HC1 There is at first formed, without doubt, diazobenzene chloride, CeH 5 N :N.C1, and aniline, which subsequently react with each other. When the secondary aromatic amines are heated they are converted into the primary; the tertiary into the second- ary, etc. Thus, the iodomethylate of dimethyl aniline, C 6 H5.N(CH 3 )3l, at 220-230 C., gives the hydriodide of di- methyl toluidine: CH 3 .C 6 H 4 .N(CH 3 ) 2 .HI; and the latter, heated still higher, gives hydriodide of methyl- xylidine, (CH 3 )2.C 6 H3.NH(CH 3 ).HI; and at 335 C. there is formed the hydriodide of trimethyl- amido-benzene : (CH 3 ) 3 .C 6 H 2 .NH 2 .HI. This isomerization may be explained by a dissociation of the ammonium derivative and the action of RI on the compound. The R group takes the ortho or para position with reference to the nitrogen, but never the meta. 222 ORGANIC SYNTHESES. Pyridine compounds behave in the same manner when heated: C 5 H 5 N.C2H 5 I, heated to 320 C. for some hours, is con- verted into the hydriodide of ethylpyridine, C5H4(C2H 5 )N.HI. This method is applied to the preparation of the homologues of pyridine. Isomerization affords a method for the synthesis of the diamine derivatives, starting from the hydrazo compounds. 1 Thus, hydrazobenzene, C 6 H 5 .NH I , C 6 H 5 .NH under the influence of acids, gives benzidine: C 6 H4.NH 2 In the same manner, hydramines, heated to 130 C., or by boiling with potash, are converted into a stable nucleus : C 6 H 5 .CH:N X C 6 H 5 .C.NH >CH.C 6 H 5 . || C 6 H 5 .CH:N/ C 6 H 5 .C.NH k C 6 H 5 .C.NtL >CH.C 6 H 5 . || >CH.C 6 H5. . V C 6 H 5 .C.NH/ Hydrobenzamide. Amarine. An interesting fact is the reciprocal transformation by heat of the two isomers of dichlortolane, using 63 and 143 C.: C 6 H 5 .C.C1 C 6 H 5 .C.C1* 1 By the action of energetic reducing agents on azo bodies, which give hydrazo- compounds, the latter isomerizing as above. ISOMERIZATION. 223 This isomerization, along with others (fumaric and maleic acids, etc.), can only be explained by considering the spatial relations of the atoms in the molecule, and by admitting, with Wislicenus, that one of the isomers is piano-symmetrical and the other axio-symmetrical. 1 In these cases, as with dichlortolan?,, where two different bodies are represented by the same formula, the isomerization is called tautomerism. When one and the same body is decomposed differently under the influence of different chemical agents, a single formula does not suffice to explain its reactions; two formulas are required, giving a different distribution of the atoms in their spatial relations in the mole- cule. Thus, aceto-acetic ester, C 3 H.CO.CH 2 .CO.OR, under certain conditions behaves like a compound having the formula, CH 3 .C(OH):CH.CO.OR. Phloroglucol (trioxy-benzene 1:2:4) sometimes behaves as a triketone : CO HzC/NcHa OCX/ CO * CH 2 Optically inactive substances (but containing an asym- metric carbon atom) can be converted into different isomers by different decompositions. The simple crystallization of the salts is sometimes sufficient, as in the case of tartaric, malic, phenylglycollic acids, etc. In the same manner, artificial a- propylpyridine (the salt) gives an isomer which rotates the plane of polarized light to the right. This double nature appears to disappear when one or several isomers are mixed together, when the different rotatory powers mutually annul one another. The splitting-up of a substance into two isomeric bodies may sometimes take place through the agency of a micro-organ- ism which will destroy one of the isomers. Thus, with amyl 1 See Butt. Soc. Chim., vol. 49, p. 457. 224 ORGANIC SYNTHESES. alcohol, CH(CH 3 )(C 3 H 7 )OH, there is formed, by the aid of fer- ments, a Isevo-gyrate alcohol. Glyceric acid, CO.OH CH.OH , CH 2 .OH behaves in the same manner. With conicine, there cannot be obtained by this method the optically active isomers, on account of its destructive action on inferior organisms. INDEX A. PAGE Acetal 1 159 preparation of 164 Acetamide 175 Acetanilide 1 70 Acetic acid, removal of 126 Aceto-acetic acid 144 Aceto-acetic ester 107 Aceto-anthramine 175 Aceto-chlor-hydrin 161 Aceto-ethyl mercaptol 166 Acetone 189 Aceto-nitrile 103 Aceto-oxalic ester 199 Aceto-phenone 70, 145 Acetoxime 160 Acetyl chloride 40, 75 Acetyl-para-toluidine, oxidation of 17 Acetylene hydrocarbons, isomerization of 218 tetrabromide 202 /3-Acetyl-propionic acid 44 Acid amides, action of bromine on 74 conversion of, into acids 43 NH 2 group in 42 chlorides 160 group, effect of, on oxidations 1 8 nitriles, preparation of 207 reducing agents, action of, on azo-bodies 63 Acids, esters of 113 Acids, reduction of 51 Acrolein -ammonia 119 Adipic acid 211 Air, oxidizing action of 1 1 225 226 INDEX. PAGE Alanine 96 Alcohols, oxidation of, to aldehydes 12, 25 reaction of, with amines 169 reduction of 55 removal of 127 Aldehydes 1 50 chlor-substituted 53 condensation of 191 nitration of 87 oxidation of 5,12,23 reaction of, with amines 171, 172 reduction of ." 53, Aldehydine 172 Aldol 136 Aldoximes 92,117 Aliphatic amines, separation of 93 Alkamines 119 Alkylamines 119 Allophanic esters 152 Allyl alcohol, oxidation of 9 benzene 201 chloride 201 cyanide. 1 54 dimethyl-carbinol 189 iodide 76, 1 32 thio-urea 46 Allylene 1 56 Amarine, oxidation of 26 Amides of di-acids, conversion of, into salts 43 Amidines 140 Amido-acetamide 94 Amido-aceto-phenone 198 Amido-acids 167 Amido-ammonium salts 43 /9-Amido-butyric acid 140 Amido-compounds, nitration of 86 Amido-ethers, decomposition of 44 Amido-group, substitution of 58 Amido-oximes 140 Amido-sulphonic acids 102 Amines, action of halogens on 74 chlorine derivatives of 40 nitrites of 41 of the paraffin series 41 removal of 127 Ammo-acids 124 INDEX. 227 PAGE Ammonia-aldehydes 198 Ammonia derivatives, preparation of 93 fixation of 139, 148 removal of 1 20 Ammoniacal chloride of zinc 195 Ammonium derivatives 167 Amyl alcohol 50, 224 Amylene 1 50 Anhydrides, preparation of 162 reaction of, with amines 171 Anilides 147 Aniline 73 oxidation of 10 reduction of 50 Anthramine 96, 175 Anthraquinone 142 oxime 92 Anthrol 96 Antipyrine 77 Aromatic aldehydes, oxidation of 24 reduction of 53 amines, separation of 94 compounds, condensation of, with acids 198 oxidation of 7 hydrocarbons, action of halogens on 69 nitration of 85 Aromatic-hydroxy acids, removal of water from 114 nitriles 117 Asparagine i3 8 Aspartic acid 62 Atropic acid 1 3 1 Aurine 97 Azines 173 Azo-benzene 60 oxidation of 35 Azo-compounds 62, 1 78 oxidation of , 35 Azo-phenylene 169 Azoxy-benzene 60 Azoxy -compounds 1 80 B. Benzaldehyde 53 Benzaldehydine J 72 Benzaldoxime l6 228 INDEX. PAGE Benzene disulphonic acid 45 hexahydride, derivatives of 61 oxidation of 20, 35 a-Benzene-pinacoline 219 Benzene ring, replacement of halogen by OH in 38 Benzene-sulphinic acid 139 Benzhydrol 80, 162 Benzidine 222 Benzoates, formation of 184. Benzo-hydroxy-meta-carboxylic acid 54 Benzoin 56 Benzonitrile 207 Benzophenone 55, 99, 212 Benzophenone-meta-carboxylic acid 54 Benzoquinone-oxime 93 Benzoyl-acetic acid 200 Benzoyl-acrylic acid 145 Benzoyl-benzoic acid 200 Benzoyl chloride 40, 80 Benzoyl-f ormic ester 44 Benzyl-acetamide 1 70 Benzyl-acetic acid * 144. Benzyl-aceto -acetic acid 144. Benzyl alcohol 55 amine 53. cyanide 91, 205 ether 55 iodide 89 Benzylidene-acetone, oxidation of 1 1 Benzylidene chloride, oxidation of 37 Bisulphites, fixation of 139 Borneol 1 50 Brom-acetic acid 75 Brom-anthraquinone 39 Brom-benzyl bromide 206 Brom-ethyl acetate 89 Brom-ethylene I3 1 Brom-naphthylamine 164 Brom-nitrobenzene 94 Brom-nitro-benzoic acid 65 Brom-nitro-ethane 89 a-Brom-/?-nitro-naphthalene 64 Brom-nitro-naphthalene 64. Brom-nitro-toluene - 69 /?-Brom-propionic acid 89 Brom-succinic ester l *& INDEX. 229 PAGE. Brom-tri-brom-phenol 218 Bromine, fixation of 133 oxidizing action of 1 1 removal of no substitution of by chlorine 74 by iodine 76 Butylamine, normal 41 secondary 41 Butyric acid, oxidation of 15 C. Camphoric acid, constitution of 21 Caproic acid, oxidation of 33 Carbamic acid 140 Carbohydrates 147 Carbon dioxide, fixation of 183 disulphide 140 reaction of, with amines 174 monoxide, fixation of 182 removal of 122 tetrabromide 175 tetrachloride 175 Carbonic acid, removal of 123 Carbonyl chloride 160, 168 Carboxyl-ketonic acids 107 Carboxylic acids, nitration of 86 reaction of, with amines 1 70 synthesis of 210 Carbylamine, preparation of 207 Caustic potash, action of in oxidations 114 CH group, conversion of into C.OH 19 oxidation of 19, 20 CH.CH group, conversion of, into CO.CO 20 CH 2 group, conversion of, into CO 19 oxidation of 19 CH 3 group, conversion of, into CO.OH 16 conversion of, into CHO 15 oxidation of 15, 16 oxidation of, in phenols 17 CH 2 OH group, conversion of, into CHO 23 CH 2 .OH group, oxidation of 22 Chlor-acetamide 94 Chlor-acetic acid 75 Chlor-acetic-anilide 1 70 230 INDEX. PAGE Chlor-acetic-ester 78 Chlor-aldehyde 191 Chlor-benzene 68 Chlor-dinitro-benzene 95 Chlor-dinitro-phenol 39 Chlor-ethyl-acetate 94 Chlor-formic acid 160 Chlor-iodo-ethylene 89 Chlor-malyl chloride 8 1 Chlor-nicotinic acid 57 Chlor-nitrobenzene 94 Chlor-nitrotoluidine 95 Chlor-platinate salts 77 -Chlor-propionic acid 109 a-Chlor-quinoline 39 /5-Chlor-quinoline 40 7--Chlor-quinoline 40 Chlor-sulpho-cymene 57 Chloral 53 Chlorine, fixation of 132 formation of compounds of 35 removal of . 109 substitution of, by bromine 75 substitution of, by fluorine 77 substitution of, by iodine 75 Chlorine derivatives, conversion of, into iodine compounds 76 Chloroform 145 CHO group, oxidation of 23 substitution of, by CH 3 53 CH.OH group, oxidation of 21 Choline. .- i, 23 Chromic acid, action of, in oxidations 13 mixture 13 Chromyl chloride, action of, in oxidations 13 preparation of 1 6 Chrysoidine 178 Cinnamic acid 191, 192 oxidation of 30 Cinchomeronic acid ". 66 Citric acid 144 CO group, conversion of, into CH 2 54 into CH.OH 53 into C.OH 53, 187 Collidine : . . . . 119 Combustion 15 Condensation with loss of water 191 INDEX. 231 PAGE Conicine 224 oxidation of 25 Copper spiral, action of, in oxidation 1 1 Coumaric acid 114 Coumarine 136, 193 Cresol, oxidation of 14 Croton aldehyde 136 Crotonic acid 140, 194 oxidation of 9 aldehyde 119, 191 Cumalic acid 214 Cuminic acid, oxidation of 219 alcohol 55 Cyanimide 155 Cyanethine 216 Cyanhydrins 96, 187 Cyanic acid 151 Cyanides, oxidation of 25 Cyanogen 137, 154 chloride 138 Cyan-phenine 216 Cyanuric acid 215 ester 215 Cymene 55 oxidation of 8, 18 D. Desoxalic acid 123, 215 Desoxybenzoin 56 Dextrose 161 Diamido-anthraquinone 97 Diamidogene 63 Diamido-imido-fluorescein 98 Diamines, derivatives of 176 Dianthramine 1 75 Diazo-acetic acid 200 ester 78 Diazo-acids 119 esters of 44 Diazo-amido compounds 59. *77 Diazo-benzene-sulphonic acid 100 Diazo-chlorides 59 group, substitution of 58 Dibenzyl, oxidation of 10, 25 Di-brom-nitro-ethane 91 232 INDEX. PAGE Dibrom-propionic acid, oxidation of 37 Dibrom-toluene, oxidation of 38 Dichlor-nitrobenzene 39 a-Dichlor-propionic acid, oxidation of 37 Dichlor-propionyl chloride 95 Dichlor-tolane 222 Diethylamine 121 Di-imides, derivatives of 1 76 Di-isopropyl bromide 219 Diketones 142 Dimethyl-acetamide 43. Dimethyl-acetylene 218 Dimethyl-amido-benzoic acid 204. Dimethyl-aniline 83, 204. Dimethyl-ethyl-carbinol, oxidation of 29 Dimethyl-nitramine 43 Dimethyl-toluidines 83 /3-Dinaphthylamine 96 Dinitrobenzoic acid 65 Dinitro compounds, preparation of 89 Dinitro-ethane 89 Dinitro-mesitylenic acid 85 Dinitro-stilbene 211 Dinitro-toluene 65 Dinitro-toluidine, oxidation of 117 Dioxy-acetophenone 198 Diphenic acid 115 Diphenyl 212 oxidation of 34 Diphenyl-ethane 196 Diphenyl-methane 55, 202 Diphenyl-propane 201 Diphenyl-succinic acid 206 Diphenyl-thiourea 1 74 Direct oxidation with decomposition of molecule 29 Dithio-carbamic acid 121 Dithionic acid 47 Divanillin 213 Durol 218 E. Elements capable of oxidation 2 Erythrine tetrachloride 80 Erythrite . 80 oxidation of 22, 29 INDEX. 235 PAGE Esters, formation of 158 saponification of 146 Ether 158 Bthers, formation of 162 Ethyl acetate 145 Ethyl-acetylene 218 Ethyl alcohol, action of chlorine on 73 amine !" 58, 74, 75 Ethyl-benzene 67 oxidation of 1 8, 1 9, 34 Ethyl bromide 68 oxidation of 36 Ethyl-chlor-formate 211 Ethyl-ether, oxidation of 1 1 Ethyl iodide 88, 103 Ethyl-isobutyl ketone, oxidation of 32 Ethyl-nitro-acetate 89 Ethyl-nitrolic acid 91 Ethyl oxalate 199 Ethyl peroxide, formation of 25 Ethylene bromide 74 chlor-bromide 75 chloride 75 oxidation of 37 diamine 120 oxide 55, 1 1 1 perchloride no Ethylidene bromide ./. 159 chloride 67 F. Fatty acids, dry distillation of silver salts of 33 reaction of, with halogens 68 Fluorescein 97, 98 Fluorine compounds, preparation of 78 Formaldehyde, preparation of 1 1 Formamide 43 Formaniline 49 Formic acid 144 removal of 1 26 Fumaric acid no, 145 oxidation of 28 Fumaryl chloride 8 1 234 INDEX. G. PAGB Gallic acid 1 25, 2 1 3 Glacial acetic acid 163 Glucose 176 Glucosides 147 Glyceric acid 79, 224 Glycerol, oxidation of 11,12 Glycocoll 124 Glycol 80, 113 oxidation of 31 Glycollic acid 179 Glycols, anhydrides of 187 removal of water from 113 Glyoxal, oxidation of 24 reaction of, with amines 173 Glyoxime 92 Glyoxylic acid 145 Guanidine, conversion of, into urea 44 Guanidines 98 H. Halogen, removal of 109 substitution of, by HS 100 byNH 2 93 by N.OH 91 by NO 2 88 by O.NO 89 by O.NO 2 90 by SO 2 .OH 103 by sulphur 09 Halogen acid, removal of no carriers 7 compounds, preparation of 70 reduction of 48 group, substitution of, by hydroxyl 8 1 Halogens, substitution of 56 Hexachlor-benzene, oxidation of 38 Hexaethyl chloride I IO Hexoxy-benzene I 8 3 -Hexyl iodide, oxidation of 36 Hydration J 42 Hydrazines 59, 66 oxidation of 2 7 substituted *?6 INDEX. 235 PAGE Hydrazobenzene 49, 222 Hydrazo derivatives, oxidation of 26 Hydriodic acid as a reducing agent 49, 52 removal of in Hydro-atropic acid 205 Hydrobromic acid, removal of in Hydrobenzamide 172 Hydrobenzoin 185 Hydrocarbon, removal of 126 Hydrochloric acid, removal of no Hydrocollidine-dicarboxylic acid 198 Hydrocyanic acid 187 Hydrogen additive aromatic compounds, oxidation of 34 fixation of 60 substitution of, by a metal ic 6 by N.OH 93 by NO 2 group 85 by SO 2 .C1 105 by SO 2 .OH 101 Hydrogen peroxide, fixation of 139 sulphide, fixation of 139 removal of 1 20 Hydrophthalic acid 1 26 Hydropyridine compounds, oxidation of 25 Hydroquinone 54, 159, 213 Hydrosorbic acid, oxidation of 14 f-Hydroxy-acids 114 Hydroxy-acids 1 24 Hydroxy-anthraquinone 197 Hydroxy-azobenzene 179 Hydroxy-benzoic acid, condensation of 2C o Hydroxy-benzoin 56 Hydroxybenzoyl-benzoic acid 197 Hydroxyl oxygen, reduction of 48 substitution of, by NH 2 95 by NH.R 97 for halogen 35 Hydroxylamine derivatives, preparation of 82 Hypochlorous acid, fixation of 141 I. Imides 138 Imido esters 149 Indirect oxidation 35 Iodides, methods of oxidizing 36 236 INDEX. PAGE lodination 72 Iodine, fixation of 134 removal of no substitution of, by bromine 76 by chlorine 75 by fluorine 77 by hydrogen 56 Iodine trichloride 71 lodo-acetic acid 79 lodo-aniline 74 lodo-benzene 89 lodo-ethyl alcohol 89 lodo-ethylene 89 /?-Iodo-propionic acid 211 lodo-stearic acid in Jodoform 50, 75 Iso-butyl iodide, oxidation of 36 Iso-butylene 1 36 oxidation of 30 Iso-butyric acid, oxidation of 19 aldehyde 1 86 Iso-caproic acid 114 Iso-cyanic esters 140, 151 Iso-dialuric acid 173 Iso-dibrom-succinic acid 126 Iso-glucosamine 178 Iso-nitriles 1 38, 2 20 Iso-nitro-aceto-acetic ester 90 Iso-nitro-propane 82 Iso-nitroso-ketones 91 Iso-nitroso-malonic ester 90 7-Iso-nitroso-valeric acid 44 Iso-phthalophenone 204 Isoprene 215 Iso-propyl-benzene 201 Iso-propyl-bromide 58 Iso-propyl-chloride 58, 67 Jso-propyl-dimethyl-carbinol, oxidation of 29 Iso-propyl-iodide, oxidation of 36 Iso-sulpho-cyanides 121, 140, 153 Isomerization 217 INDEX. 237 K. PAGB Keto-amides 43 Ketones, condensation of 192 nitration of 97 oxidation of 5, 32 reduction of 53 Ketonic acids 54, 125, 144 aldehydes, reduction of 56 oxygen, reduction of 48 Ketoximes 92 L. Lactic acid 54 Laevulose 176 Laevulinic acid 114 M. Malic acid 81 Malonic ester 146 Manganese dioxide, action of, in oxidation 12 Mellitic acid 123 Mercaptans 165 Mesityl oxide 145 Mesitylene 192 oxidation of 19 Meta-chlor-benzoic acid, oxidation of 38 Meta-chlor-phenol 41 Metacrylic acid 113 Meta-nitro-benzoic acid 69 Meta-phenylene diamine 178 Metallic salts of organic acids 106 Metallo-organic derivatives, preparation of 106 Meta-styrol 215 Methyl-acetamide 43 Methyl amine 93 Methyl-butyl-ketone, oxidation of 33 Methyl-formamide 170 Methyl-malonic acid 123 Methylene iodide 5 Milk sugar, oxidation of * n Mixed ethers 158 Mono-chlor-acetic acid, oxidation of 37 Muscarine l 23 8 INDEX. N. - PAGE Naphthalene, oxidation of 34 ^-Naphthylamine 64, 96 NH group, substitution of , by S 100 conversion of, into 44 NH 2 group, displacement of, by OH 41 joined to CO, conversion of, into OH 43 method of preventing oxidation of 17 substitution of, by halogen 77 by HS loo byN0 2 87 by SO. 2 OH 104 Nicotinic acid 57, 125 Nitric acid, action of, in oxidations 14 derivatives, preparation of 82 Nitrile radical, substitution of 58 Nitriles 136, 140 conversion of, into esters 44 polymerization of 216 Nitrites of secondary amines 1 18 Nitro-compounds, bromination of 71 reduction of 48, 63 separation of, from nitrous esters 88 substitution of 58 Nitro-amido-benzoic acid 118 Nitro-anilides 86 Nitro-benzene 70 action of bromine on 71 Nitro-benzyl alcohol 197 Nitro-carboxylic acids 124 Nitro-chlor-benzene 39 Nitro-dichlor-benzene 100 Nitro-naphthalene 122 a-Nitro-naphthalene 102 Nitro-nitriles, reduction of 65 Nitro-phenols , 96 Nitro-phthalene 122 Nitroso-phenyl-urea 138 Nitro-styrol 85 Nitro-sulphonic acids 85 Nitro-toluene, oxidation of 13, 18 Nitrolic acids 82 Nitrosamines 83 reduction of 63 Nitroso-anilide 84 INDEX. 239 PAGE. Nitroso-anilide, reduction of 64 Nitroso compounds, reduction of 63 Nitroso-dimethyl-aniline 58, 83, Nitroso group, substitution of 58- Nitrosyl chloride, fixation of 141 Nitrous acid, action of, on aliphatic alcohols 84- on imido compounds 84 on nitro-compounds 82 derivatives, preparation of 82 N : N group, conversion of, into H.OH 44. substitution of, by halogens 78- N.OH group, conversion of, into 43 NO 2 group, influence of 39 Normal propyl bromide 201 O. Octyl bromide 210 CEnanthol 191 (Enanthylic acid, oxidation of 33. aldehyde 151 OH group, conversion of, into H 55 introduction of, with silver salts 37 substitution of, by halogen 79 by SOH - 104 Oleic acid 135 oxidation of 28- Ortho-amido-anilides 117 Ortho-iodo-phenol, oxidation of 3& Ortho-nitro-benzal-acetone, oxidation of 10 Ortho-nitro-phenol 39 Ortho-nitro-toluene 64 Ortho-oxy-benzoic acid 46 Ortho-sulpho-amido-toluene 116 Ortho-toluene-sulphonic acid 46 Ortho-toluic acid, oxidation of 17 Oxamic acid 171 Oxamide 171 Oxidants, action of 10- Oxidation as result of condensation 9 direct 15 methods of conducting 8- phases of 2 with ammonia derivatives 41 Oxidizing agents, action of 8, 1 1 Oximes 62- 240 INDEX. PAGE Oxy-acids, action of phosphorus pentachloride on 8 1 formation of 185 nitration of. ..." 87 Oxy-anthraquinone 39 a-Oxy-carboxylic acids 113 a-Oxy-iso-butyric acid 144 ^x-Oxy-nitriles, reaction of, with amines 169 Oxy-pyridine 55 Oxy-pyrone 98 Oxygen, action of 1 1 fixation of 131 removal of 60 substitution of 60 by I 2 82 by NH 97 by N.OH 92 by sulphur 99 in CO group ....,* 81 P. Palmitolic acid, oxidation of 28 Para-amido-benzoic acid 167 Para-amido-phenol, oxidation of 26 Para-brom-aniline '. 69 Para-chlor-ortho-toluidine 64 Para-nitro-aniline 42 Para-nitro-benzyl chloride 90, 211 Para-nitro-phenyl-propiolic acid 133 Para-nitro-toluene 69, 7 1 Paraldehyde 151 Para-phenylene diamine, oxidation of 26 Para-rosaniline, formation of 10 Penta-methylene-diamine 1 20 Phenanthraquinone-oxime 92 Phenates 184 Phenazine 69 Phenol 68, 69 acid esters of 105 action of bromine on 73 Phenol-aldehydes 193 Phenol bromide 57 Phenol, ethers of 163 Phenols, making of 41 nitration of 96 INDEX. 241 PAGE Phenols, oxidation of 14, 20 reaction of, with amines 169 reduction of 55 Phenol-sulphonic acid 46 Phenyl-aldehyde 1 44 Phenyl-brom-acetic acid 20 5 Phenyl-carbimide 168- Phenyl-chloroform, oxidation of 67 Phenyl-cyanate 215 Phenyl-ethylene oxide 113 Phenyl-glycidic acid 125 Phenyl-glycocoll 1 70 Phenyl-glycol 113 Phenyl-hydrazine 1 76 Phenyl iodide 132 Phenyl-lactic acid 144 Phenyl-pyrazol 176 Phenyl-urea 175 Phloroglucic acid 125 Phloroglucol 125, 223 Phorone 192 Phosphonium iodide 50 Phosphorus halides, use of 80 Phosphorus, use of, with hydriodic acid 49 Phthalic anhydride 196 Phthaleins 55 Phthalimide, reduction of 53 Phthalophenone 204 Phthalyl-acetic acid 194 Phthalyl chloride 204 Picoline '. 119 Piperidine, oxidation of 25 Piperonal 122 Platinum spiral, action of, in oxidations 1 1 Polyhydric phenols, oxidation of 20 Polymerization 215 Potash, fusions with 38 Potassium permanganate, action of, in oxidations 12 persulphate 1.05 Primary alcohols, oxidation of 5 amines, action of heat on 175 oxidation of 26 nitro compounds 91 Propane, oxidation products of 6 Propargylic alcohol . 159 Propylene bromide 58 242 ^ INDEX. PAGE Propylene chloride 58 a-Propylene chloride 132 Propyl-phenyl-ketone, oxidation of 16 Propyl-pseudo-nitrol 83, 1 31 Protocatechuic aldehyde 122 Pseudo-cumene, oxidation of i & Pseudo-nitrols 82 Pyrazolines 62, 220 Pyrazols 62 Pyridine-carboxylic acids 125 Pyridone derivatives 97 Pyrocatechin 169 Pyrogallol 125 Pyromellic acid 123 Pyromucic acid 198 Pyrone 97 Pyrotartaric acid 215 Pyruvic acid 54, 112 Q. Quinic acid, oxidation of 34. Quinoline 55 carboxylic acid 125 oxidation of 34. Quinone 54 Quinone-dioxime 93. Quinone-oximes 92, 1 32 Quinone, reduction of 53 Quinoxalines 173 R. Radicals capable of oxidation 2 Reducing agents, action of 49 Reduction, different forms of 48 Removal of halogens 109 hydrogen 109 oxygen 109 Resorcin 163, 213 oxidation of 14, 20 Rhodamine 97 Rhodizonic acid 183 INDEX. 243 S. PAGE Salicyl aldehyde 192 anilide 86 Salicylic acid 87, 194 Secondary alcohols, Chancel's reaction for 89 oxidation of 5 hydrocarbons, substitution of , by Cl 67 Side-chains, influence of position of, on oxidation 7 oxidation of 7 Silver oxide, action of, in oxidations 12 ammoniacal solution of 12 Simple ethers, removal of 127 Skraup's synthesis 214 Sodium acetanilide 184 amalgam 50 as a reducing agent 50 stannite 5 Soluble starch, action of oxidants on 12 SO 2 .OH group, substitution of, by OH 105 Stannous chloride as a reducing agent 51 Styrol 215 Substituted acids, replacement of halogen by OH in 38 Substituents of the first group 68 second group 68 Substitutions, laws of 67 Succinamide 1 20 Succinic anhydride c 150 Succinimide 1 20 Succinyl chloride 52 oxalic acid 199 Sulph-acetic acid 103 Sulphine acids 60 Sulphinic acid 139 Sulphocyanic acid 153 Sulpho-mesitylenic acid 185 Sulphonal ! 166 Sulphones 101, 166 Sulphonic acid group, conversion of, into OH 45 substitution of 60 Sulphonic acids, action of bromine on 174 amides of 43 chlorides of 40, 57, 95, 161 fusion of, with caustic potash 45 lead, salts of 45 244 INDEX. Sulphur, displacement of, by O ........................ . ......... , . 46 preparation of compounds containing ....................... 165 substitution of ........................................... 60 by NH ................................... 9 & Sulphuric acid, esters of ........................................... 105 fixation of ......................................... 139 anhydride, fixation of .................................... 1 39 removal of ................................... 121 Sulphurous anhydride, fixation of .................................. 139 Sulphuryl chloride ................................................ 105 Synthetic sugar .................................................. 22 T. Tartaric acid 81, 215 Tartronic acid 124, 146 Tautomerism 225. Terebenthene, oxidation of 20 Terpene 141 Tertiary alcohols, oxidation of 5, preparation of 190- amines 155 amyl iodide, oxidation of 36 Tetrabrom-phenol 2 1 & a-Tetrahydro-naphthylamine, oxidation of 35 Tetramethyl-benzene 2i& Tetramethyl-diamido 4 -fluorescein 97 Thio-amides 98- Thio-anilides. 99 Thio-benzanilide 99 Thio-butyric acid 120 Thio-carbamic acid 121 Thiophene 119 Thiophenyl-urea 46 Thio-urea 98, 128: substituted 1 20- Thymol 1 26 Tin as a reducing agent 51 Toluene 70 oxidation of 1 1 Triacetonamine 119* Triacetonine 119 Triamido-azo-benzene 179* Tribrom-phenol 57 bromide 57 INDEX. 45 PAGR /?-Trichlor-acetyl-acrylic acid 145 Trichlor-lactic acid, oxidation of 37 Trichlor-phenol 104. Triethyl-phosphine 215 Triethyl-sulphuric iodide 156 Trimethyl-carbinol, oxidation of 29 Trimethylene no Trimethyl-ethylene bromide 218- Trimethyl-rosaniline 97 Trinitro-mesitylene 65 Triphenyl -brom-methane 36 Triphenyl-chlor-methane 202 Triphenyl-guanidine 1 74 Triphenyl-methane 202 oxidation of 20- Triphenyl-urethane 197 U. Unsaturated acids, synthesis of 192 alcohols, oxidation of 27 compounds, oxidation of 14 groups, reduction of 48 hydrocarbons, oxidation of 27 Uramido-benzoic acid 175 Urea 164 synthesis of 219 Urethanes 152 Uric acid, oxidation of 31 V. Valerianic acid 211 Valeric acid 215 Valero-lactone 114 Valerylene 215 Vanillin 213 oxidation of 24 W. Water, fixation of 135 removal of 112 246 INDEX. X. PACK Xylene 71 hexahydride, oxidation of 25 Z. Zinc as a reducing agent 51 dust as a reducing agent 51 ethyl 132 propyl 190 X^BR^lrxN OF THE ;; UNIVERSITY \ UF ~ THIS BOOK IS DUE ON THE LAST DATE STAMPED BELOW AN INITIAL FINE OP 25 CENTS WILL BE ASSESSED FOR FAILURE TO RETURN THIS BOOK ON THE DATE DUE. THE PENALTY WILL INCREASE TO SO CENTS ON THE FOURTH DAY AND TO $1.OO ON THE SEVENTH DAY OVERDUE. SEP 32 1! NOV 11 NOV 17 1944 MAY 3 1S45 22 ' LD 21-100m-7,'39(402s) 2/678 . UNIVERSITY OF CALIFORNIA LIBRARY