GIFT OF ORGANIC CHEMISTRY INCLUDING CERTAIN PORTIONS OF PHYSICAL CHEMISTRY FOR MEDICAL, PHARMACEUTICAL, AND BIOLOGICAL STUDENTS (WITH PRACTICAL EXERCISES) BY HOWARD D. HASKINS, A.B., M.D. Professor of Biochemistry, Medical Department, University of Oregon Formerly Associate Professor of Organic Chemistry and Biochemistry, Medical Department, Western Reserve University THIRD EDITION, THOROUGHLY REVISED TOTAL ISSUE, FIVE THOUSAND NEW YORK JOHN WILEY & SONS, INC. LONDON: CHAPMAN & HALL, LIMITED 1917 COPYRIGHT, 1907, BY H. D. HASKINS AND J. J. R. MACLEOD COPYRIGHT, 1917, BY t\ HOWARD D. HASKINS PRESS OP BRAUNWORTH & CO. BOOK MANUFACTURERS BROOKLYN. N. Y. PREFACE TO .THIRD EDITION IN this edition the subject matter has been rearranged to a considerable extent. Numerous revisions have been made. The discussion of the physical chemistry topics has been amplified, and, hi some cases, partly re- written (e.g., osmotic pressure and colloids). It will gratify the author greatly to receive for consideration suggestions and criticisms from any who are using this text-book. HOWARD D. HASKINS. PORTLAND, OREGON. Nov. 1, 1916. iii 380850 PREFACE TO SECOND EDITION THE author has endeavored to revise the entire book, striving to make it more reliable as a reference book, and more complete from the standpoint of the student of medical sciences. It is our belief that an organic chemistry text-book for the use of medical students should give the chemistry of all the organic compounds (of any importance) that enter into the study of physiology, biochemistry, and pharma- cology. H. D. HASKINS. July 1, 1912. iy PREFACE TO FIRST EDITION AMONG the most important of the recent advances in medical science are those relating to the chemistry of the various organic substances which enter into the composition of animal tissues and fluids, and to the physico-chemical laws which govern, or at least influence, many physiological processes. The dis- covery of the chemical constitution of the purin bodies, of many of the urinary constituents, and of sugars and fats, as well as the new theories of solu- tion and catalysis, has revolutionized the teaching of biological and clinical chemistry; and in phar- macology and pharmacy a knowledge of organic and physical chemistry is almost essential. The study of these parts of chemistry is, therefore, daily coming to be of greater importance to the medical student and is already included in the curriculum of the best medical schools. 1 As taught in the regular college classes in organic chemistry, the subject certainly absorbs too great a proportion of the medical student's time, and much is included in the course which has no bearing on 1 The recent application by Arrhenius of certain physicochemical laws in explaining the mode of action of antitoxins, etc., is an illustration of the increasing importance of a knowledge of physical chemistry for the medical student. Vi PREFACE his future work, and much is omitted which is of immense importance to him. It was with the idea of presenting in the simplest manner the facts of organic and physical chemistry which have an essential bearing on medical science that the present book was written. For the sake of simplicity, the subject-matter is arranged in a some- what different manner from that usually followed in text-books for chemical students. In the first por- tion of the book considerable attention is given to a description of the methods employed for purifying and testing the purity of substances preparatory to their further investigation. It is to this part of his work that the investigator in bio-chemistry has to give his closest attention and in which he often meets with the greatest difficulties. A chap- ter giving a fairly full description of the methods of elementary analysis follows, and then a chapter on the principles of physical chemistry as applied to molecular weight determinations and to the theories of osmosis, solution, etc. Those facts of physical chemistry which it is desirable to call attention to that are not included in this chapter are inserted where they can most conveniently be studied along with the organic compounds. The remainder of the book includes a description of the various groups of organic substances, and, where possible, there is chosen, as the representative of each group, some body of medical or biological importance. Numer- ous practical exercises accompany the text, and these have been chosen and arranged so as to occupy about four hours of laboratory work per week for a thirty- PREFACE vii week session. A few more advanced exercises are given for the sake of completeness, and it is left to the teacher whether or not he shall have them performed by the student. The cyclic compounds and the more complicated of the benzene deriva- tives may also be omitted at the discretion of the teacher. In the Appendix will be found a schedule showing how the work of the class in our own institution is arranged so that all the members of it may do those experiments involving the use of expensive apparatus. The laboratory work is required of our students. We believe that by conducting an elementary analysis and by doing cryoscopic experiments with Beck- mann's apparatus, as also preparing pure organic compounds, the student acquires an idea of accuracy and an insight into the principles of chemical methods which he cannot otherwise obtain, and which, without any doubt, will be of immense value to him in all his future work. Our experience is, also, that students of whom laboratory work is required get a grasp and understanding of the subject of organic chemistry such as others rarely acquire. H. D. HASKINS. J. J. R. MACLEOD. April, 1907. CONTENTS CHAPTER I. PAGE THE NATURE AND COMPOSITION OP ORGANIC COMPOUNDS ... 1 CHAPTER II. PURIFICATION AND IDENTIFICATION OF SUBSTANCES 7 CHAPTER III. ELEMENTARY ANALYSIS 28 CHAPTER IV. MOLECULAR WEIGHT DETERMINATION. THE NATURE OF SOLU- TIONS. OSMOTIC PRESSURE. IONIZATION. SURF ACE TEN- SION. VISCOSITY. COLLOIDAL SOLUTIONS 40 CHAPTER V. FORMULAE, EMPIRICAL AND STRUCTURAL. ISOMERISM 98 SYNOPSIS OF CHAPTERS I-V 100 CHAPTER VI. PRELIMINARY SURVEY OF ORGANIC CHEMISTRY 101 SYNOPSIS OF FATTY COMPOUNDS 115 CHAPTER VII. SATURATED HYDROCARBONS. METHANE SERIES 117 ix X CONTENTS CHAPTER VIII. PAGE HALOGEN SUBSTITUTION PRODUCTS OF THE PARAFFINS 124 CHAPTER IX. ETHERS 132 CHAPTER X. PRIMARY ALCOHOLS : . , 136 CHAPTER XI. ALDEHYDES 146 CHAPTER XII. FATTY ACIDS AND ETHEREAL SALTS. FURTHER OBSERVATIONS IN PHYSICAL CHEMISTRY 157 CHAPTER XIII. SECONDARY AND CERTAIN OTHER MONACID ALCOHOLS. KETONES 189 CHAPTER XIV. DIACID ALCOHOLS AND DIBASIC ACIDS 193 CHAPTER XV. \ TRIACID ALCOHOLS, FATS, AND SOAPS 199 CHAPTER XVI. HYDROXY-ACIDS 212 CHAPTER XVII. CARBOHYDRATES AND GLUCOSIDES 227 CHAPTER XVIII. NITROGEN DERIVATIVES. (ALSO PHOSPHORUS AND ARSENIC COMPOUNDS.) 255 CONTENTS xi CHAPTER XIX. PAGE AMINO ACIDS AND ACID AMIDES 266 CHAPTER XX. ACID IMIDES. COMPLEX AMINO AND IMIDO COMPOUNDS, INCLUDING POLYPEPTIDES 284 CHAPTER XXI. UNSATURATED HYDROCARBONS AND THEIR DERIVATIVES 299 CHAPTER XXII. SULPHUR DERIVATIVES 306 CHAPTER XXIII. CYCLIC AND BI-CYCLIC COMPOUNDS 309 CHAPTER XXIV. THE AROMATIC HYDROCARBONS 316 CHAPTER XXV. AROMATIC HALOGEN DERIVATIVES 333 CHAPTER XXVI. AROMATIC HYDROXY COMPOUNDS 336 CHAPTER XXVII. AROMATIC ACIDS 356 CHAPTER XXVIII. AROMATIC NITROGEN DERIVATIVES. . . 374 xii CONTENTS CHAPTER XXIX. PAGE SULPHUR AND ARSENIC DERIVATIVES 391 CHAPTER XXX. QUINONES, DYES AND INDICATORS 398 CHAPTER XXXI. AROMATIC COMPOUNDS HAVING CONDENSED RINGS 409 CHAPTER XXXII. HETEROCYCLIC COMPOUNDS 414 SYNOPSIS OF AROMATIC COMPOUNDS 423 CHAPTER XXXIII. ALKALOIDS AND DRUG PRINCIPLES 425 APPENDIX. NOTE TO THE INSTRUCTOR 443 REFERENCE TABLES I. Specific Gravity and Percentage of Alcohol 445 II. Weight of Pure Gas in 1 c.c. of Moist Nitrogen at Various Temperatures and under Various Pressures . . 447 III. Specific Gravity and Percentage of NaOH in Aqueous Solution 448 IV. Specific Gravity and Percentage of KOH in Aqueous Solution 449 V. Acetic Acid, Specific Gravity and Freezing-point at Various Concentrations 450 VI. Vapor Tension of Water and of 40% KOH at Various Temperatures 450 VII. Dissociation Constants of Certain Organic Acids 451 VIII. Dissociation Constants of Certain Bases 451 IX. Power of Certain Acids to Cause Hydrolysis 452 CONTENTS xiii ILLUSTRATIONS. PAGE FIG. 1. Melting-point Apparatus 10 2. Sublimation Apparatus after Gattermann 14 3. Fractional Distillation Apparatus after Gattermann. 15 4. Fractionating Column after Gattermann 15 5. Steam Distillation Apparatus after Gattermann .... 16 6. Vacuum Distillation Apparatus after Gattermann. . . 17 7. Boiling-point Flask 18 8. Picnometer 23 9. Westphal's balance 23 10. Hydrometer 24 11. Combustion furnace 30 12. Calcium Chloride and Potash Absorption Apparatus after Gattermann 31 13. Mixing Tube 32 14. Nitrogen Burette after Gattermann 37 15. Victor Meyer's Vapor Density Apparatus after Walker 45 16. Pfeffer's Osmotic Pressure Apparatus 49 17. Beckmann's Apparatus and Thermometer after Walker 61 18. Flashing-point Apparatus after Remsen 122 19. Ethyl Bromide Apparatus after Gattermann 126 20. Aldehyde Apparatus after Fischer 152 21. Acetyl Chloride Apparatus after Gattermann 167 22. Tartaric Acid Models, Illustrating Stereoisomerism . . . 223 23. Sodium Ammonium Racemate Crystals after Holle- man 224 24. Ethylene Bromide Apparatus after Gattermann 301 25. Collie's Benzene Model .324 ORGANIC CHEMISTRY CHAPTER I THE NATURE AND COMPOSITION OF ORGANIC COMPOUNDS Definition of Organic Chemistry. The various inor- ganic chemical compounds are classified by the chem- ist into groups, a group comprising all the com- pounds of some particular element. Thus we have the iron group, the sulphur group, and so on. On account, however, of the great number 1 of compounds containing the element carbon, the group of carbon compounds is set apart for consideration as a special branch of chemistry. Organic chem- istry is that branch: it is the chemistry of carbon compounds. This definition is, however, not strictly accurate, for it is customary to treat of the oxides of carbon and the carbonates in inorganic chemistry. The name organic owes its 'origin to the old-time belief that these compounds of carbon could be pro- duced only by the agency of vegetable or animal organisms, by so-called vital activity. That such a notion is untenable was first shown by Wohler, who, in 1828, obtained urea the main organic 1 About 150,000. CHEMISTRY constituent of urine by simply evaporating an aqueous solution of ammonium iso-cyanate, his intent being to recrystallize the latter salt (p. 278). Since that date thousands of organic compounds have been prepared in the laboratory without any assistance from vital processes. In fact, a great proportion of the compounds known to organic chemists have never been discovered in nature, but have been created in the chemical laboratory. Elements and Their Detection. In organic com- pounds carbon may exist in combination with one, two, three, four, or even five other elements. The most important elements present in organic com- pounds, together with their atomic weights and valences, are as follows: Carbon C, atomic wt. 12, valence IV. Hydrogen, H, " " i, " I. Oxygen, O, " "16, " II. Nitrogen, N, " "14, " III and V. Phosphorus,?, " "31, " III and V. Sulphur, S, " "32, " II, IV and VI. Some important compounds contain the halogens (Cl, Br, I). The presence of most of these elements in organic compounds can be quite readily detected by simple tests, the principal ones being incorporated in the experiments that follow. The presence of oxygen cannot be directly determined; it is detected by rinding the percentage composition of the com- pound and observing that the sum of the per cents of all the other elements is less than one hundred. ORGANIC COMPOUNDS 3 EXPERIMENTS. Detection of carbon, hydrogen, nitrogen, sulphur, phosphorus and chlorine. (1) C and H. Dry a clean test-tube in the gas- flame. Fit it with a cork through which passes a glass tube bent at a right angle. Mix in a mortar a little dry cane sugar and ten times as much dry CuO, pour this mixture into the test-tube, cork, and dip the outside end of the glass tube into baryta solution contained in another test-tube. Heat the sugar mixture over a flame. Drops of water con- dense on the cool parts, showing the presence of H. 1 Cloudiness in the baryta is due to carbon dioxide, BaCOs having been formed, and indicates the presence of C. By heating, CuO is reduced; its oxygen combines with the C and the H of the organic substance to produce CO2 and EbO. (2) N and S. (a) Triturate in a mortar some dry albumin with twenty times as much soda-lime, 2 transfer the mixture to a test-tube, and heat over a flame. Test the vapor that appears for ammonia, the presence of which proves the existence of N in the compound examined. (6) Put into a dried test-tube some dry albumin equal in bulk to a bean. Add a small piece of clean metallic sodium. Heat until the mass is red-hot, then gently drop the test-tube into a mortar contain- ing 10 c.c. of distilled water. The tube breaks, and NaCN and Na 2 S go into solution. Grind 1 Water of crystallization must be removed before testing for hydrogen. 2 Soda-lime is made by gradually adding powdered quick- lime to a saturated solution of caustic soda with constant stirring. 4 ORGANIC CHEMISTRY up the charred mass with the pestle. Filter and divide the filtrate into portions A, B, C, and D. To A add NaOH until strongly alkaline, then a few drops of freshly made FeSO* solution l and a drop of FeCls solution. Boil this mixture two minutes, cool, and acidify with HC1. The appearance of a greenish-blue color or a precipitate of Prussian blue indicates N. To B add a few drops of a fresh solution of sodium nitroprusside; 2 a reddish-violet color points to the presence of S. To C add lead acetate solution and acidify with acetic acid. A brownish-black discoloration or precipitate is due to S. Neutralize D with HC1; add a few drops of FeCls solution; a red color, which is removed by HgCb, is caused by the presence of sulphocyanide. If sulphocyanide is not formed in examining an organic compound by this method (it is not formed if a sufficient excess of sodium is used), halogens may be tested for in the filtrate by boiling some of it with one-tenth volume of concentrated HN0 3 (HCN or H 2 S driven off, prolonged boiling may be necessary to remove all the HCN) and then testing with AgN0 3 (precipitate of AgCl, AgBr, or Agl). In this test iodine and bromine are set free by the nitric acid and can be detected by conducting the vapor into a test-tube containing a little CS 2 (for this test heat the mixture in a short test-tube and close the tube with a stopper having a bent tube as in exp. 1). If it is desired to detect N, S, or halogens in a liquid it is best to drop the liquid on melted sodium contained in a test- tube that is held vertically by being thrust through a hole in an asbestos pad. 1 Sodium ferrocya'nide is formed by this treatment. Formula =Na 2 Fe(CN) 6 (NO). ORGANIC COMPOUNDS 5 (3) Cl. Put a little pure powdered soda-lime in a dry test-tube, add as much chloroform as it will soak up, and heat strongly. Break the tube and powder the mass in a mortar. Treat with strong HNOs until dissolved. Test with AgNOs. A control test with soda-lime alone should give only a slight turbidity. (4) P. Mix some dry nucleoprotein (or dry yeast) with twenty parts of fusion mixture (1 part Na2COs +2 parts KNOs). Heat in a crucible until the mass is almost white. When cool, dissolve it in a little hot water and pour the resulting solution into an evaporating dish. Add HC1 until neutral and filter. To half of the filtrate add NH 4 OH until strongly alkaline, then add magnesia mixture. 1 The phos- phates, formed by the oxidation of the phosphorus of the compound, cause a white precipitate. To the other half of the filtrate add HNOs until strongly acid, then add an equal volume of ammonium molybdate solution 2 and heat in a water bath until a fine yellow precipitate appears. Having thus determined what elements are pres- ent in the organic compound that he is investigating, the chemist next proceeds to its more thorough 1 Magnesia mixture is made as follows: Dissolve 55 gm. of pure MgCl 2 crystals and 70 gm. NH 4 C1 in 1300 c.c. of water and add 350 c.c. of 8% ammonium hydroxide. 2 Ammonium molybdate solution is made as follows: Dis- solve 75 gm. of powdered ammonium molybdate in 250 c.c. of water with the aid of heat, and add (when cool) 35 c.c. of C.P. NH 4 OH. Pour this into a mixture of 300 c.c. of C.P. HN0 3 and 675 c.c. of water while stirring vigorously. 6 ORGANIC CHEMISTRY examination. He first estimates the percentage amounts of the various elements contained in the substance, and then he determines its molecular weight. He is able from these data to calculate the empirical l formula. But more than one sub- stance may have this same formula; therefore he studies the reactions of the compound when treated with reagents in order to get a clue as to how its molecule is built up, that is, how its atoms are linked together. And, finally, by causing simpler substances, the structure of the molecules of which is known, to become united (synthesis), he endeavors to produce a substance having the same molecular structure as his compound. If his synthetic com- pound shows properties that are identical with the substance under examination, the chemist then considers that he has established with absolute certainty the chemical construction of the com- pound. But all this work will end in failure unless the sub- stance under examination be absolutely pure, i.e., free from admixture of any other substances. It is necessary for us at this stage, therefore, to explain the chief methods of purification as well as the tests by which the purity of the substance is ascer- tained. This will be done in the chapter that follows. 1 The empirical formula gives merely the total number of atoms of each element in one molecule, as C*Hi 2 (see p. 98). CHAPTER II PURIFICATION AND IDENTIFICATION OF SUBSTANCES PURIFICATION OF SUBSTANCES THE main methods of separating an organic sub- stance in a pure state are crystallization, sublimation, distillation, extraction and dialysis. Crystallization. The basis of this method is the fact that different substances are not usually solu- ble to an equal extent in the same solvent. For example, acetanilide can be separated from dex- trose by dissolving the mixture of these two in hot water; when the resulting solution is cooled, the acetanilide crystallizes out because of its slight solubility in cold water, while the dextrose remains in solution. By repeated crystallization in this manner perfectly pure acetanilide can be obtained (see exp. below). Inasmuch as crystallization as a method for separation and purification of organic compounds is invaluable, it will be well to detail specific direc- tions for carrying it out. (1) Carefully select a suitable solvent. Put small quantities of the sub- stance to be purified into several test-tubes; and add to each a different solvent (those most commonly used are water, alcohol, ether, chloroform, benzol, 7 8 ORGANIC CHEMISTRY petroleum ether, acetone, and glacial acetic acid). Discard those that dissolve the substance readily. Heat each of the remaining. Choose the solvent which when hot dissolves the substance readily, but deposits crystals on cooling. The solvent should either hold the impurity in solution when cold or exert no solvent action on it whatever. (2) Completely saturate at boiling temperature a certain quantity of the chosen solvent with the sub- stance. (3) Filter the hot liquid through a plaited filter, using a funnel with a short stem. (With a long- stemmed funnel crystals may separate out in the stem and block it.) Heating the funnel in hot water before filtration may be resorted to. (4) Collect the filtrate in a beaker having a capacity twice the volume of the liquid. With too small a beaker creeping of crystals and liquid may occur. (5) Cool slowly. 1 If crystals are deposited very quickly, redissolve with the aid of heat, and pre- vent rapid cooling by wrapping the beaker with a towel. (6) Cover the beaker with a piece of filter-paper to prevent condensation-drops from falling back into the liquid and disturbing the crystallization. A watch-glass or glass plate completes the covering. (7) Do not disturb the beaker until crystals have formed. If their appearance is greatly delayed they may often be induced to form by scratching the inner 1 5, 6, and 7 may be disregarded except when the form of the crystals is to be studied. PURIFICATION OF SUBSTANCES 9 wall of the beaker with a glass rod, or by " sowing " a crystal of the substance into the liquid. (8) If the substance is not sufficiently insoluble in the cold solvent, crystallization may be brought about by slow evaporation in a loosely covered crystallization dish. (9) Collect the crystals on a suction-filter (reject the crystals that have crept above the surface of the liquid), and wash them with a little of the pure cold solvent. (10) Dry the crystals in a desiccator, except when they contain water of crystallization. EXPERIMENT. Put 20 c.c. of distilled water into a beaker and heat to boiling on an asbestos pad. Completely saturate it with the mixture of dextrose and acetanilide which is furnished. Filter while hot, and cool rapidly. When a good crop of crystals has formed, separate them by filtration. Dissolve in a little water and recrystallize. Repeat the proc- ess until the filtrate from the crystals no longer gives reduction when boiled with Fehling's solution. 1 At least three crystallizations should be carried through. Save the pure white crystals. After they are dried in a desiccator a determination of the melting-point may be made (see below).. 1 Fehling's reagent consists of an alkaline solution of cupric hydroxide, the latter being held in solution by means of Rochelle salt. The reagent should be freshly prepared by mixing equal volumes of 7% CuS0 4 and of an alkali solution containing 25 gm. KOH and 35 gm. Rochelle salt in 100 c.c. The reagent is of a deep-blue color, and when it is boiled with even a trace of dextrose a red precipitate forms in it. 10 ORGANIC CHEMISTRY To test the purity of the crystals their melting- point is determined. The method of making a melting-point determination will be described in the experiments that follow. Pure crystals melt quite sharply and completely, i.e., they become completely melted within 0.5 to 1. The crystals may be considered pure when, after repeated crystal- lization (preferably from different solvents), the melting-point remains constant for several successive determinations. A bath of water may be used for substances having a low melting-point (below 80 l ). Sulphuric acid is used for higher tem- peratures (up to 280). For still higher temperatures paraffin is used. The thermometer should be one with the scale engraved on the stem. The crys- tals should be powdered and thoroughly dried in a desiccator. EXPERIMENT. Make melting-point tubes by heating a glass tube of 10 mm. diameter in a flame until a 2-cm. section is red, then drawing it out. A capillary tube about 1 mm. in diameter and 5 FlG - * or 6 feet long, is thus obtained. Break into lengths of 6-8 cm. and seal one end of each. Put into such a tube some powdered chloral hydrate that has been dried in a desiccator. Gentle scratching with a file 1 All temperatures given in this book are centigrade. PURIFICATION OF SUBSTANCES 11 will cause the particles to travel to the bottom of the tube. Attach the tube to a thermometer by means of a narrow rubber band cut off from rubber tubing, adjusting it so that the main part of the chloral will be opposite the middle of the bulb of the thermometer. Suspend the ther- mometer in a beaker of water so that the bulb is fully immersed. Heat the water very gradually. Note the temperature at which there is the first indication of melting (beginning transparency or collapsing against the wall of the capillary tube of any portion of the crystalline substance). Note also the temperature of complete fusion. The temperature nearest to the true melting-point is that recorded by the thermometer at the moment when minute droplets are first formed by the melt- ing of the fine particles that are in actual contact with the wall of the capillary tube. Into another tube put pure dried powdered urea; 1 attach the tube to a thermometer with a fine plati- num wire, adjusting it as above. The bath in this case should be pure H 2 S04 containing 30% of K 2 SO4 (to lessen fuming), contained in a long- necked Jena flask (as, for example, a Kjeldahl incineration-flask). By means of a loosely fitting cork suspend the thermometer in the flask, with its bulb dipping into the bath. In a similar manner suspend another thermometer to take the temper- ature of the air above the H 2 S04. Heat gradually. When melting occurs, place the bulb of the second 1 Where " pure urea " is called for it is best to prepare it by recrystallizing some urea from hot absolute alcohol. 12 ORGANIC CHEMISTRY thermometer midway between the meniscus of the mercury in the stem of the first thermometer and the surface of the bath; from this quickly make the reading of the air temperature (this is t in the formula below). Also measure in degrees the height of the mercury column above the surface of the H 2 S04 ( =L in the formula). The correction that must be added to the observed reading (which is T) on account of the fact that the stem of the thermometer and mercury thread is cooler than the bulb, can be calculated by the formula: L(T t) (0.000154). The coefficient of expansion of mer- cury in glass is 0.000154. The corrected 1 melting- point of pure urea is 132.6. For the most accurate work in determining melting-points careful attention to a number of things is essential. Tested thermometers of a standard thickness should be used. A set of thermometers of limited range, as 0-50, 50-100, 100-150 graduated for 0.2, would be desirable. The melting-point tube should have about the same thickness of wall as the wall of the bulb of the thermometer. The crushed crystals should be sifted through a fine-mesh screen, as variation in size of the particles gives variation in melting-point. The tube should be filled for only about 3 mm. of its length, solidly packed. The initial heating may be rapid until a temperature 20 below the melting-point is reached, when the heating should be such as to cause not over 3 rise per minute, and near the melting-point 0.5 per minute. Stir- ring of the bath is desirable. A double bath by means of which the air about the thermometer is heated as well as the liquid insures greater accuracy. Such an apparatus can be con- 1 The melting-points marked " corrected " are quoted from H. Meyer's Analyse und Konstitution der organischen Verbind- ungen. PURIFICATION OF SUBSTANCES 13 structed by taking a tall Jena beaker (17-20 by 8 cm.) and suspending in it a large test-tube (20x3 cm.). Pour into the test-tube albolene (liquid vaseline) to a depth of 5 cm., and fill the beaker for nine-tenths of its depth with the same liquid. As a stirrer use a piece of gold-plated wire, coiled in a large spiral at the end to fit loosely the inside of the test-tube. Sus- pend the thermometers in the test-tube as shown in Fig. 1. When the temperature approaches the melting-point, stir steadily. An air temperature of only 3-7 below the oil tem- perature is secured, hence it is unnecessary to calculate a cor- rection. A method of purification applicable to certain solid substances is sublimation. A substance sub- limes when it passes readily from the solid state to a vapor. The method is carried out as follows : A watch-glass or evaporating dish containing the substance is covered with iilter-paper which has several pin-hole perforations. A funnel of slightly smaller diameter is inverted over this, the stem being loosely plugged with cotton. The dish is heated gradually until vapor passes into the upper chamber of the apparatus and condenses on the cool walls of the funnel (see exp., p. 359). Distillation. This method is useful mainly for the purification of liquids. Certain solid substances, however, can be distilled to advantage. When the impurity is a material that will not vaporize at the temperature employed (i.e., at a temperature at which the substance itself readily vaporizes), simple distillation suffices. When, however, a mix- ture of volatilizable liquids is dealt with, fractional distillation has to be resorted to. This method is described in the following experiment. Certain 14 ORGANIC CHEMISTRY mixtures cannot be resolved into their constituents in the pure state by fractional distillation, such as water and alcohol, or methyl alcohol and benzol. EXPERIMENT. Set up a distillation apparatus as shown in the diagram. Into the distilling flask pour through a funnel about 300 c.c. of 70% alcohol, and drop in some short capillary tubes. Select a cork that will fit the flask tightly. Through a hole in the cork insert a thermometer, and hang it so that the bulb is in the stream of vapor, i.e., opposite or below the opening of the side tube. The bulb must not be below the neck nor low enough to be splashed by the boiling liquid. Heat on a water bath. Have four clean dry receiving flasks ready and labeled. In the first flask collect all the distillate coming over while the thermometer registers a temperature between 78 and 83. Now dry the outside of the distilling flask with a cloth and change it to an asbestos pad having a hole one inch in diameter. In the second flask collect that distilling between 83 and 88. Flask number three is to catch the distillate between 88 and 93. The last flask re- ceives all that distills over above 93. (Do not distill over all the water.) Measure the amount of each fraction, and of the residue in the flask. Drain and dry the condenser tube. For the second distillation use a smaller distilling PURIFICATION OF SUBSTANCES 15 flask or a small flask with a bulbed column attached as shown in the diagram. Pour into it the fluid in FIG. 3. flask number one and use the latter as the first receiving flask for the distillate. When the tem- perature reaches 80 pour the con- tents of flask number two into the distilling flask, and when the tem- perature again rises to 80 replace flask number one by flask number two as the receiver; also change the distilling flask to the asbestos pad as before. When the temperature reaches 83 add the liquid in flask number three to the distilling flask, and distill until the tempera- ture reaches 88. Determine the per cent of alcohol in these three fractions by taking the specific gravity of each with WestphaPs balance (see p. 24), and comparing with the table (p. 445). By repeated fractionating FIG. 4. 16 ORGANIC CHEMISTRY practically all of the alcohol is brought into flask number one, and most of the water into flask number four. As, however, it is simply the alcohol that is of value in this case, redistill the first frac- tion only and secure a distillate coming over at 78-79. This should contain at least 90% (by volume) of alcohol. Distillation is sometimes carried out by bubbling steam through the mixture, which is kept at a tem- FIQ. 5. perature of at least 100. By this means substances that boil even at 200 can be obtained in the dis- tillate, mixed, of course, with a large quantity of water (see Fig. 5). Those substances that do not have a distinct vapor pressure at 100 will not dis- till with steam. Vacuum distillation is employed in certain cases, particularly when it is desirable to lower the boil- ing-point in order to prevent any decomposition of the substance. Many substances decompose at a temperature below their boiling-points. The PURIFICATION OF SUBSTANCES 17 distilling apparatus is closed up air-tight except for a finely pointed tube which dips below the sur- face of the heated liquid and, passing through the stopper, is open to the air; through this tube fine bubbles of air keep the contents of the flask in commotion and prevent bumping. The receiv- ing flask is connected with a suction-pump. A reduction of pressure in the apparatus to 30 mm. of mercury (atmospheric pressure being about 760 mm.) FIG. 6. will usually lower the boiling-point of a high-boiling substance by nearly 100. An ordinary suction- pump is usually quite satisfactory for lowering the pressure (see Fig. 6). The test of purity of a substance that distills is con- stancy of boiling-point. If, after repeated frac- tional distillation, a material is obtained which has the same boiling-point each time and which distills over completely at that temperature, it is most likely to be a pure substance. 18 ORGANIC CHEMISTRY EXPERIMENT. The boiling-point flask should be either a long-necked distilling flask which has the side tube coming off very high up near the cork, or an ordinary distilling flask into the neck of which is fitted an open tube slightly ex- panded at the lower end so as to fit the neck, while the latter has been dented with a blast-flame at the proper point to prevent the tube from slip- ping into the chamber of the flask (see Fig. 7). In such an apparatus the vapor passes up to the cork, then descends outside the tube, heating the stem of the thermometer for the whole length of the mercury column, the thermometer being lowered sufficiently to permit this. The thermometer used should be of the same kind as those specified for melting-point determination (p. 12). Put 20 c.c. of pure chloroform into the flask; support the flask on wire gauze (it is advisable to interpose between the gauze and the flask an asbestos pad having a hole one inch in diameter). Attach a long tube as an air-condenser and place a receiving flask in position. Heat with a small flame. When vapor passes freely into the con- denser, note the temperature. Continue distilla- tion until the temperature has remained constant for at least five minutes. Take the reading as the boiling-point. No correction is necessary except PURIFICATION OF SUBSTANCES 19 for barometric pressure. This correction can be calculated approximately by adding to the ob- served boiling-point 0.038 for each mm. below 760 mm. barometric pressure or subtracting 0.038 for each mm. above this. 1 The boiling-point of chloroform at 760 mm. pressure is 61.2 (corrected). 2 The author has devised a simple apparatus by which the boiling-point can be determined under standard pressure without the calculation of a correction. 3 The special distilling flask (see Fig. 7) is connected with an air-tight condensing apparatus, a filtering flask (as receiver) being fitted to the end of the condenser. The side tube of this flask is connected with tubing containing air under pressure coming from the blower part of a large Wetzel suction pump. A calcium chloride tube or tower is interposed to prevent moisture getting into the flask. The compressed-air system is connected also with a barometer (or with a second distilling apparatus, as suggested below) of the older type bent in U form at the bottom; and furthermore is connected with a tube that is suspended in a tall cylinder of water. By raising or lowering this tube, the pressure in the distilling apparatus as recorded by the barometer can be brought to any height 1 If the boiling-point is around 100 the factor of correction is 0.044, if 150 it is 0.05, if 200 it is 0.056, and if 250 it is 0.062. For water, alcohol, organic acids, and other liquids whose mole- cules become associated (p. 69) the figures are lower; around 50 it is 0.032, 100 it is 0.037, 150 it is 0.042, 200 it is 0.046, and 250 it is 0.051. 2 The boiling-points marked " corrected " in this book are those given in Traube's Physico-chemical Methods. 3 Smith and Menzies have recognized the desirability of securing the boiling-point at this standard pressure. They recently (1910) described an apparatus for the purpose. Their method, however, makes use of a small boiling-point bulb tied to a thermometer, and submerged in a bath. 20 ORGANIC CHEMISTRY which could occur as atmospheric pressure. It must be remem- bered that a small correction of the barometer must be made for the temperature, since standard barometric pressure is 760 mm. when the scale and the mercury of the barometer are at 0. For example, if the temperature of the room is 15, the apparent pressure in the apparatus must be 762 mm. (761.9 mm. if the barometer has a brass scale), in order to get the boiling- point under 760 mm. pressure. The apparatus can be used to demonstrate the amount of change of boiling-point for definite changes of pressure. After accurately determining the boiling-point of an absolutely pure liquid that is stable and not inclined to absorb moisture (as benzene), the apparatus can be arranged to eliminate the barometer by connecting a second air-tight distilling apparatus in which to boil the liquid that is under examination. Now regulate the pressure so that the liquid of known boiling-point distills at a temperature corresponding to standard pressure as previously determined (read to 0.1); then the temperature at which the other liquid distills will be the boiling-point of the latter at 760 mm. If the liquid has a high boiling-point, shield the flask with a metal or asbestos cylinder that rests on the asbestos pad. Extraction. Not infrequently the most feasible method of separating an organic compound from a mixture is by extraction. It may be extracted from an aqueous mixture by shaking the latter with an organic solvent that is immiscible with water. If the substance that is to be extracted has a greater solubility in the organic solvent than in water, it will be extracted rapidly. In many cases the solubility of the substance in the water may be greatly diminished by saturating the solu- tion with a salt (as NaCl or CaCl 2 ), then, of course it will be more readily extracted. The principle involved in extraction is that a substance soluble PURIFICATION OF SUBSTANCES 21 in two liquids distributes itself between the two in the ratio of its solubilities in the two solvents. For instance, if a compound in aqueous solution is twice as soluble in ether as in water, then after shaking the solution with an equal volume of ether for a proper length of time, the ether will contain two-thirds of the substance and one-third will remain in aqueous solution. It follows that several succes- sive extractions with small portions of solvent is very much more efficient than a single extraction with a large volume of the solvent. If the solubilities are in the ratio of one to two (as above), extracting once by shaking thoroughly with three volumes of ether will result in one-seventh of the original amount remaining in aqueous solution; but only one-twenty-seventh will remain if the shaking is carried out three times with equal volumes of ether. If the solvent is one that takes up more than a trace of water, a drying agent should be used to remove the water. The substance extracted is recovered by distillation or evaporation of the solvent. If necessary, it may be purified further by crystallization, distillation, or by treatment with a different solvent. EXPERIMENT. Measure into a separating fun- nel 20 c.c. of saturated salicylic acid solution and 20 c.c. of ether, stopper tightly, and shake vigor- ously for ten minutes. Draw off the bottom layer, and carefully pour the ether out through the mouth of the funnel into a dry flask. Return the aqueous 22 ORGANIC CHEMISTRY solution to the funnel, add 20 c.c. of ether, and continue as above. Also extract with a third por- tion of ether. Test about 1 c.c. of the aqueous solution with a drop of dilute FeCls, and compare the faint color reaction with the intense color given by saturated salicylic acid. Treat the com- bined ether extract with a small amount of dried Na2S(>4. After it has stood for some time, pour the ether into a dry flask, and distill off most of the ether, using a hot water bath or a steam bath (have no flames near by). Now transfer the balance of the ether solution to an evaporating dish, and let the ether evaporate. Note that an appreciable quantity of crystalline residue is obtained. Dialysis is occasionally employed for purification purposes, especially in biochemistry. It depends on the well-known fact that crystalloids can diffuse through animal membranes or parchment paper, whereas colloids cannot. Thus, to separate sodium chloride from egg protein a solution containing these is placed in a dialyzer suspended in pure running water: the sodium chloride diffuses out, leaving the egg protein in the dialyzer, IDENTIFICATION OF SUBSTANCES When the substance has been purified by the above methods, identification may be attempted. For this purpose its physical properties are studied; its color, odor, and taste are carefully noted, and determinations are made of its melting-point, boiling-point, crystalline form including measure- IDENTIFICATION OF SUBSTANCES 23 ment of the angles of the crystals, density or specific gravity, action on polarized light, spectroscopic appearance, refractive power, and solubilities. The data thus obtained are compared with those of known substances. Aside from the first five properties mentioned, the most universally useful one for purposes of identi- fication is specific gravity. The method of determin- ing this will be considered next. Descriptions of the FIG. 8. FIG. 9. methods of ascertaining other properties will be found in the larger laboratory manuals. 1 The specific gravity of liquids may be found by several different methods: 1. The weight of equal volumes of the liquid and of water may be successively determined in a special stoppered bottle called a picnometer. The temperature of both fluids at the moment of weighing must be reported. 1 Gatterman. The Practical Methods of Organic Chemis- try. Translated by Schober. Mulliken. Identification of Pure Organic Compounds. Lassar-Cohn. Laboratory Manual of Organic Chemistry; also, Arbeitsmethoden fur organisch-chemische Laboratorien. 24 ORGANIC CHEMISTRY The temperature of the water taken as the stand- ard for comparison may be 0, 4, or 15. The most convenient form of picnometer is one which holds exactly 10, 25, or 50 gm. of pure boiled water at 15 (see Fig. 8). Further details are explained in the experiment below. 2. Westphal's balance is a very useful instrument for finding specific gravity (see Fig. 9). Riders of different sizes are used on this balance, each one representing a different decimal place in the specific gravity. This instrument gives the specific gravity of the liquid at the temperature of observa- tion compared with pure water at 15. 3. The hydrometer is another empirically graduated instrument for determining specific gravity, water at 15 being the standard. It is a glass float having a long stem; this sinks in the liquid, so that the surface of the latter is on a level with a certain mark on the stem, and the figures that are read off at that mark indicate the specific gravity (see Fig. 10). The urinometer is a hydrometer for use with urine. The specific gravity of a solid can be found (ft) by weighing it in the air, then reweighing it while immersed in water. This method has very little application in organic chemistry. The specific gravity of crystals or small solids can be determined by placing an accurately weighed quantity of them in a picnometer filled with some liquid in which they are insoluble (see exp. below). IDENTIFICATION OF SUBSTANCES 25 EXPERIMENTS, (a) Specific gravity of petroleum ether. Weigh accurately an empty dry picnometer which will hold just 25 gm. of pure water at 15; deduct from the weight 0.027 gm. for the weight of the contained air. Remove the stopper and fill with petroleum ether (boiling at 60-70). Wrap a strip of folded filter-paper about the neck to catch the overflow, insert the stopper so that no air is left in the bottle, wipe off gently, and re weigh. When weighed, note the temperature as indicated by the thermometer in the stopper, and observe whether air has been drawn into the bottle* by cooling and consequent contraction of the fluid. The difference between the two weights gives the weight of the petroleum ether, and this divided by the weight of an equal amount of water (25 gm.) gives the specific gravity as compared with water at 15. In record- ing specific gravity report the temperature of obser- 18 vation; for example, petroleum ether /Sr-^=0.67 lo means that the specific gravity of petroleum ether at 18 is 0.67 when compared with water at 15. Also determine the specific gravity of the ether with the Westphal balance. (6) Specific gravity of urea. Weigh a little test- tube which contains pure dry urea crystals. Re- move the stopper of the picnometer and pour the urea into the petroleum ether. Tap the picnometer to cause the air adhering to the crystals to be dis- lodged. Now fill the neck with more petroleum ether, insert the stopper as before, and reweigh. The petroleum ether must be at the same temper- 26 ORGANIC CHEMISTRY ature as before. Reweigh the urea tube; by deduct- ing this weight from the previous one find the weight of the urea in the picnometer. To find how much petroleum ether has been displaced by the urea '(the latter being insoluble in the former) add to the weight of the bottle filled with petroleum ether (exp. a) the weight of the urea, then deduct from this sum the weight of the bottle containing urea immersed in petroleum ether; the difference is the weight of the petroleum ether displaced. Divide this by the specific gravity of petroleum ether; the result indicates the displacement in cubic centimeters, or rather the weight (in grams) of an equal quantity of water, so that the weight of the urea used divided by this figure gives the specific gravity. The specific gravity of urea is about 1.33. If the substance under investigation is known to chemists it can generally be identified by comparing the data gathered as to its properties with tabulated lists 1 of boiling-points, melting-points, specific gravities, etc. Generally an accurate determina- tion of the boiling- or melting-point and of the specific gravity will definitely locate the substance. When dealing with a liquid it is advisable, if there exists any doubt about the nature of the substance, to determine the specific gravity at several different tables may be found in Physikalisch-chemische Tabellen by Landoldt and Bornstein, Chemiker-Kalendar by Biedermann (yearly]editions), Melting- and Boiling-Point Tables by Carnelly. IDENTIFICATION OF SUBSTANCES 27 temperatures. When relying on melting-point for identification, it is of value to bear in mind that two different substances may have nearly the same melting-point, but a mixture of them melts at a far different temperature. Therefore, mix some of the known substance with that which is supposed to be identical with it and determine melting-point; if this is the same as for the unknown substance, then identification has been completed. If the substance is still unknown or cannot be positively identified, an accurate analysis is made to determine the percentage by weight of each element present in it. CHAPTER III ELEMENTARY ANALYSIS The estimation of the carbon and hydrogen pres- ent in a compound is made by combustion in the presence of cupric oxide, the end-products of com- bustion being carbon dioxide and water. The method is in principle exactly the same as that for the detection of carbon and hydrogen. The combustion is carried out in a glass tube of difficultly fusible glass having an inside diameter of about 1.5 cm. This tube should be 10 cm. longer than the furnace in which it is to be heated; 85 cm. is a good length. A tube of this length is charged for combustion as follows: a short roll or spiral of copper gauze is inserted and pushed in 5 cm. from the end; moderately coarse cupric oxide (of wire form) is poured into the other end until it occupies 35-40 cm. of the tube next to the spiral; then another short copper spiral is pushed down to the coarse oxide to hold the latter in place. The next 20 cm. of the tube is occupied by the substance to be analyzed mixed l intimately with fine cupric oxide 1 The substance may be placed in a little platinum or porce- lain boat instead of being mixed with CuO. If a liquid is to be analyzed it is sealed in a little glass bulb having a long capillary tube and the tip of the tube is broken off when the bulb is placed in the boat. 28 ELEMENTARY ANALYSIS 29 (wire form) in the manner described in the experi- ment below. A short copper spiral (which has a wire loop attached) is inserted and finally some coarse cupric oxide may be added. Each end of the tube is closed with a rubber stopper. Through the stopper at the end nearest the fine oxide mixture passes a glass tube, which is connected with the apparatus for purifying the incoming air or oxygen. The absorption apparatus which collects the prod- ucts of combustion is connected directly with a glass tube passing through the stopper at the other end. When a tube is in service for the first time, to insure complete removal of any organic matter that might be clinging to the glass or the copper oxide, the fine oxide is used unmixed with any other substance, and the whole tube is heated for several hours while a stream of dry air is passing through. In this case an ordinary calcium chloride tube takes the place of the absorption apparatus. If moisture has collected in the tube toward the end, it must be removed by warming the tube at that point. A stream of air can be used for the combustion proc- ess. Pure oxygen, however, is very much better for substances that do not oxidize readily, because of the rapidity and completeness of combustion in its presence. With oxygen, completion of the process is indicated when the outgoing stream from the absorption apparatus causes an ember on the end of a splinter of wood to glow brightly. It may add to the understanding of the process to trace the air or oxygen stream through the whole ELEMENTARY ANALYSIS 31 apparatus (see Fig. 11). It first bubbles through a strong solution of caustic potash, which removes most of the carbon dioxide; then passes through a large U-tube or drying-tower containing soda- lime or small pieces of NaOH, which removes the last traces of carbon dioxide; then through another U-tube containing calcium chloride, which removes FIG. 12. moisture. 1 The dry gas passes into the combustion- tube; when it reaches the fine copper oxide it aids the oxidation of the organic substances, and carries along with it the carbon dioxide and steam pro- duced, also any volatilized material that has not lf ro insure thorough drying the air is sometimes finally bubbled through sulphuric acid. In this case H 2 S0 4 must also be used as the absorbent in the place of the calcium chloride tubes (see Fig. 12). 32 ORGANIC CHEMISTRY been oxidized, and brings them into contact with the coarse copper oxide, which completes the oxida- tion; thus the stream when it reaches the end of the tube consists of air or oxygen containing car- bon dioxide and water- vapor. In passing through the calcium chloride tube of the absorption appara- tus the water is absorbed, and finally in bubbling through the caustic potash solution of the absorp- tion bulbs the carbon dioxide is removed; the slight amount of moisture picked up here is removed by the straight calcium chloride tube (see Fig. 12). The details of the method are given in the following experiment. EXPERIMENT. Combustion analysis of salicylic acid. After the combustion-tube has been charged FIG. 13. and thoroughly heated as directed above, remove the stopper at the end nearest the air-tank, quickly pour out the coarse oxide into a clean dry beaker, pull out the short spiral, and finally pour out the fine oxide into another beaker and replace the stopper. Put the beakers and the spiral into a desiccator. Weigh accurately a weighing-bottle containing about 0.2 gm. of pure salicylic acid that has stood in a desiccator several days. Through a clean short- stemmed funnel pour the salicylic acid into the mix- ing-tube (see Fig. 13) ; add some of the fine oxide carefully through the funnel in such a way that all the crystals of salicylic acid are carried along with ELEMENTARY ANALYSIS 33 the CuO into the mixing-tube. When the tube is half full, insert the stopper; hold the tube and stop- per firmly and shake very vigorously. When well mixed, quickly empty the contents into the com- bustion-tube; rinse the ' mixing-tube by shaking successively with small portions of fine oxide until all the oxide has been transferred to the combustion- tube. Replace the spiral and pour in the coarse oxide. Replace the stopper, connect with the air- purifying apparatus, and start the air-stream. The CaCl 2 tube remains at the other end of the tube. Reweigh the weighing-bottle. Begin lighting the burners at the end near the cal- cium chloride tube, starting one burner at a time and with the lowest flame possible, then very grad- ually increasing the flames in number and size. Do not heat near the fine oxide. In the meantime weigh the calcium chloride absorption-tube and the caustic potash bulb with its calcium chloride tube (remove the plugs before weighing), and attach them in place of the ordinary calcium chloride tube. When the coarse oxide has been brought to a dull red heat, the part of the tube that contains this having been covered with tiles, start the heating of the other end of the tube, very grad- ually, beginning at the far end. Stop the air-stream. When the fine oxide is heated, watch closely, and turn down the burners here if bubbles pass too rapidly through the potash bulbs. The bubbles should not go so fast that they cannot be easily counted (three in two seconds). Finally, bring the whole tube to a dull red heat (never hotter). When 34 ORGANIC CHEMISTRY bubbles cease to pass, combustion is practically complete; but continue the heating of the tube for thirty minutes (fifteen if oxygen is used) while passing a slow air-stream (which will give the proper rate of bubbles). Then begin to cool the tube by gradually turning down the burners from each end, but do not remove the tiles. Examine the end of the combustion tube for condensed water; if present, vaporize it by careful heating at that point. If oxygen is used, change to an air-stream at this point so as to clear oxygen out of the absorption tubes before reweighing. During the first fifteen minutes of cooling pass the air-stream more rapidly to sweep out of the tube all water- vapor and carbon dioxide. Disconnect the absorption tubes, put on the plugs, and allow to cool in the balance room for one hour. When cool, reweigh after removing the plugs. Do not forget to attach the calcium chloride tube in the place of the absorption appara- tus. Before the combustion-tube is used for another analysis, it should be heated for an hour while dry air is passed through it. The KOH solution in the potash bulbs should not be used for more than two combustions. The increase in weight of the U calcium chloride tube indicates the weight of the water produced by the combustion. One-ninth of this is hydrogen; therefore the per cent of hydrogen present in the substance burned can be obtained by the following formula : wt. of H 2 produced X 100 Per cent H 9 Xwt. of substance burned* ELEMENTARY ANALYSIS 35 The increase in weight of the potash bulb and straight calcium chloride tube is equal to t'he weight of the carbon dioxide produced. Carbon represents TT of this; therefore for calculating the per cent of carbon the formula used is: , ~ wt. of C0 2 produced X3 X 100 Per cent C= . 11 Xwt. of substance burned The sum of the per cents of hydrogen and carbon deducted from 100 gives the per cent of oxygen. If the substance contains nitrogen, oxides of nitro- gen may be formed when the substance is oxidized as above. This necessitates a special modification of the method, because these oxides are absorbed by caustic potash. A long copper spiral (12-15 cm.), which has been reduced to pure copper by dipping it while hot into alcohol, 1 is put into the end of the tube nearest the weighed absorption apparatus in the place of part of the coarse oxide. When the nitrogen oxides come in contact with the hot reduced copper, they are deprived of their oxygen by the copper, and nitrogen is set free. Of course a free stream of air or oxygen cannot be used in this case until combustion is complete, otherwise the reduced copper spiral would become oxidized and be rendered useless. The air-stream is used to clear carbon dioxide out of the tube at the start before the heat is applied to the reduced copper spiral; during combustion the air is shut 1 By this treatment any oxide adherent to the copper yields up its oxygen to oxidize the alcohol to aldehyde. 36 ORGANIC CHEMISTRY off; when combustion is complete the air-stream is again turned on to remove all the products from the tube. // halogens are present in the substance to be analyzed a silver spiral must be used in place of the reduced copper spiral. The silver combines with the halogens and prevents their passing into the absorption tubes, where they would be absorbed. When - sulphur or phosphorus is present lead chromate takes the place of the cupric oxide in the tube. The sulphur or phosphorus is fully oxidized, and is held in the tube as sulphate or phosphate of lead. To estimate the nitrogen alone in an organic sub- stance the same tube as that described above for nitrogenous substances can be employed, provided a stream of dried carbon dioxide gas, instead of air, is used for removing the gases, etc., produced by the combustion and for clearing out the nitrogen and oxygen contained in the tube before the heating is begun. The absorption apparatus in this case is a gas burette (a burette closed with a glass cock at the top) having some mercury in the bottom to act as a valve, and filled with a 40% solution of caustic potash (see Fig. 14). When bubbles no longer collect at the top of the burette and the latter remains full of caustic (i.e., when only carbon dioxide is passing out of the tube) , the carbon dioxide is shut off and combustion is carried out by heating the tube gradually up to a red heat. When com- bustion is completed carbon dioxide is passed again until the tube is cleared of nitrogen, as shown by ELEMENTARY ANALYSIS 37 the constancy of the volume of the gas in the burette. The caustic potash absorbs all the pro- ducts of combustion except nitrogen. The burette is allowed to stand for an hour to come to room temperature, the alkali being leveled up in the appa- ratus. The caustic potash in the reservoir is brought to exactly the same level as that in the burette, and the number of cubic centi- meters of gas is read off. The temperature of the ni- trogen is found by placing a thermometer against the burette, with the bulb at the mid-level of the gas. The barometric reading (corrected for temperature) must also be taken. The results of the analysis are then computed by referring to specially prepared tables, which give in grams the amount of nitrogen corre- sponding to 1 c.c. of the moist gas in the burette, at various temperatures and under various pressures (see Appendix, p. 447). In order to use the table for nitrogen collected over alkali, add to the baro- metric pressure the difference between the vapor pressure of water and that of 40% potassium hydroxide at the temperature of observation (see Table VI, p. 450). FIG. 14. 38 ORGANIC CHEMISTRY An easier method of nitrogen estimation is the Kjeldahl method, by which the nitrogen in the organic substance is converted into ammonia by heating with pure sulphuric acid. The ammonium sulphate produced can then be treated with alkali, and the ammonia thus liberated distilled into a measured quantity of standard acid. From the amount of this latter which is thus neutralized, the amount of nitrogen contained in the organic substance can readily be calculated. A few organic compounds do not give a correct nitrogen estimation by the Kjeldahl method. This method is extensively employed in biochemical analysis and will be found fully described in many of the laboratory manuals on that subject. Oxygen is not estimated directly, but is calculated by deducting from one hundred the sum of the per cents of all the other elements present. After the percentage composition is determined, a provisional formula for the compound may be found as follows: divide the percentage number of each element by its atomic weight, divide each of the resulting figures by the smallest of them (as the greatest common divisor *), and make use of these smaller figures, or the nearest whole number, to express the number of atoms of each element in one molecule. The following example will illus- trate this. Alcohol was found by one analysis to contain 52.05% C, 13.13% H, and 34.82% O. Then J In many cases some other common divisor will have to be used. ELEMENTARY ANALYSIS 39 i C 52.05-12= 4.337; 4.337-^-2.176=1.993 H 13.13- 1=13.130; 13.130^2.176=6.030 O 34.82-16= 2.176; 2.176*2.176 = 1.000 Therefore the formula may be C2H 6 0. The same percentage composition would, however, be shown by any substance having the formula C2 n H 6n O n . It becomes necessary then to determine the number of atoms in the molecule by finding out the molecular weight; the value of n is thus discovered, so that it becomes possible to write the correct empirical formula, CHAPTER IV MOLECULAR WEIGHT DETERMINATION. THE NA- TURE OF SOLUTIONS. OSMOTIC PRESSURE. IONIZATION. SURFACE TENSION. VISCOSITY. COLLOIDAL SOLUTIONS MOLECULAR WEIGHT DETERMINATION BY ANALYSIS OF DERIVATIVES THE molecular weight of a substance can be deduced from a quantitative analysis of its deriva- tives. This method is most easily applied to acids and bases. Take, for example, a simple acid, such as acetic. By analysis, its formula might be CH 2 O, or any multiple thereof. By forming its silver salt and estimating the amount of silver in it, this will be found to be 64.6%. Now, knowing that the atomic weight of silver is 107.9 and that it is monovalent, and having ascertained that only one silver acetate occurs (showing that the acid is monobasic), we can see what formula agrees with this proportion of silver in silver acetate. Suppose this salt to have the formula CHOAg, then the per cent of Ag must be -X 100 =78.8. Obviously CH 2 O cannot be the 136.9 correct formula for acetic acid. If we take C 2 H3O 2 Ag as the formula, the per cent of silver will be ^ X 100 = 64.6% ; therefore C 2 H 4 O 2 is the correct 166.9 40 MOLECULAR WEIGHT DETERMINATION 41 formula. In the case of bases, their chlorplatinates have been found to be the most suitable compounds to form for this purpose. MOLECULAR WEIGHT .OF GASES AND VAPORS In order to understand fully the physico-chemical nature of solutions and the subject of molecular weight determinations, it will be advisable briefly to review some of the fundamental points in chem- istry that relate to these subjects. As we shall see later, gases and solutions in their physico-chemical behavior are very much alike, so that a clear con- ception of the gas laws, which are well known and readily tested, will enable us to study more satis- factorily the nature of solutions. The three important gas laws are as follows: 1. Gay-Lussac's or Dalton's law: provided its pressure remains unchanged, every gas expands by -2^3 of its volume at for each degree of rise of tem- perature. Thus a gas occupying a volume of 1 liter at will occupy 2 liters at 273, if the pressure remains constant. In making calculations it should be remembered that the absolute temperature of is 273, and therefore for any temperature above the absolute temperature is that temperature plus 273. Another way of stating the law is that the volume of a gas (at constant pressure) varies directly with its absolute temperature. 2. Boyle's law: provided the temperature re- mains constant, the volume of a gas varies inversely as the pressure. Thus, if 1 liter of gas be compressed 42 ORGANIC CHEMISTRY into the space of 0.5 liter, the pressure has been doubled. 3. Avogadro's hypothesis: under the same con- ditions of temperature and pressure, equal volumes of all gases contain the same number of molecules. The relative weights of equal volumes of different gases, under the same conditions of temperature and pressure, must represent the relative weights of the molecules (Avogadro's hypothesis). If, then, we take the weight of one gas as the standard, the molecular weights of other gases can readily be ascertained. Hydrogen is the gas thus chosen, and since its molecule contains two atoms, we ascribe to it a molecular weight of 2. Similarly, oxygen has a molecular weight of 32, being sixteen times heavier than hydrogen. Two grams of hydro- gen at and 760 mm. Hg pressure has a volume of 22.4 liters. But 2 is the molecular weight of hydrogen; therefore if we take the number of grams of any other gas equivalent to its molecular weight this amount of gas will also occupy a volume of 22.4 liters (at and 760 mm.). Such a weight in grams corresponding to the figures for the molec- ular weight is called a gram-molecule or a mole. In consequence of Boyle's law it must follow that if we compress a mole of any gas at to the volume of 1 liter, it will have a pressure of 22.4 atmospheres (i.e., 22.4x760 mm. Hg). If, therefore, we know the volume, temperature, and pressure of a known weight of a gas, it is easy by applying the above laws to determine its molec- ular weight. As an example, suppose that 0.2 MOLECULAR WEIGHT DETERMINATION 43 gm. of a dry gas has a volume of 50 c.c. at 10 and 740 mm. Hg; what is the molecular weight? 070 50 X X~ =46.899 -c.c at and 760 mm. 273 -f- 10 760 But a mole occupies 22,400 c.c. Then 0.2 gm. is 46.899 ' of a mole, therefore the mole is 95.4 gm. The molecular weight is 95.4. Vapors obey the same laws as gases. Substances, solid or liquid, that can be vaporized by heat sub- mit to a molecular weight determination as readily as gases. In practice the determination is made either by weighing a known volume of the substance in the form of vapor, or by measuring the volume of the vapor produced from a known weight of the substance. A known volume of vapor is weighed when Dumas' method is used. By this method an indefinite quantity of the substance is vaporized in a flask- like bulb by heating the bulb in an oil-bath. The neck of this flask-like bulb is drawn out to a fine tip. When all the air is displaced from the bulb, and the substance is completely vaporized, the tip is sealed off in a flame. The temperature of the bath is recorded, also the barometric pressure. After cooling, the weight of the substance in the bulb and the capacity of the latter are accurately deter- mined, and from these data the molecular weight can be calculated. This method, while simple in principle, is nevertheless tedious in practice. 44 ORGANIC CHEMISTRY A much more useful method for general purposes is that of Victor Meyer, in which the volume of a known weight of vapor is ascertained by finding how much air is displaced in a closed apparatus when the substance changes to a vapor. The apparatus/ as shown in the figure, consists of an elongated bulb continued above into a long neck closed at the top by a rubber stopper; from the neck passes a side tube, which is connected by heavy rubber tubing with a gas burette. The bulb is suspended in a wide tube having a bulb-like expansion at its closed end (the upper two-thirds of this tube should be wrapped with asbestos paper) and containing some liquid with a boiling-point 40-50 above the vaporization temperature of the substance. EXPERIMENT. Fill the bulb of the outer tube two-thirds full of distilled water; suspend the inner tube in it by means of a cork (this will have to be cut in two and then wired together again). By means of this cork also hang a thermometer in the steam-chamber and insert a bent glass tube as a steam- vent. Now boil the water (start the heating very gradually). When the thermometer registers a constant temperature, i.e., the boiling-point of 1 An excellent modification of this apparatus has been made by Bleier and Kohn, by which, instead of measuring air-displacement, the increase of pressure (the volume of gas in the apparatus being constant) due to the vaporization is measured by means of a mercury manometer. Before making an estimation the air-pressure in the apparatus is lowered by a suction-pump. MOLECULAR WEIGHT DETERMINATION 45 the water, 1 connect the side tube with the gas burette and cork the inner tube tightly with a rubber stopper. Bring the water in the burette and in the reservoir to exactly the same level. If there is no variation from this level for 5-10 minutes, the apparatus is ready for making an estimation. The entire column of air in the narrow tube has now come to the temperature of the steam surrounding it. Remove the stopper of the inner tube and place in position (supported by the glass rod, which fits the extra branch tube and extends into the neck of the main tube, as shown in Fig. 15) a little sealed glass bulb containing a known weight of pure chloroform (the bulb hav- ing been weighed before and after filling). Fit the stopper tightly, and wait a few minutes to determine whether the volume of the air in the apparatus remains constant (as indicated by the level of the liquid in the burette). When constant, fill the burette exactly to the cock by raising the reservoir after having brought the burette into communication with the outer air by means of a two-way cock (either the cock of the 1 Boiling-point at 735 mm. barometric pressure is 99.1, at 740 mm. 99.3, at 745 mm. 99.4, at 750 mm. 99.6, at 755 mm. 99.8, and at 760 mm. 100. FIG. 15. 46 ORGANIC CHEMISTRY burette or one specially inserted in the rubber tubing connection). Then close the cock, so that the burette communicates only with the air of the system. Now drop the bulb to the bottom of the Victor Meyer tube by pulling the rod. Some glass wool has been put into the bottom of the tube to prevent injury. Vapor forms and hot air is pushed over into the burette. Level up the water in the burette with that in the reservoir. When the level remains absolutely constant for a few moments, close the cock of the burette. After allowing sufficient time for cooling, measure the volume of the air displaced into the burette in exactly the same way as in nitrogen estimations (see p. 37), correcting for temperature, also for aqueous (see Appendix) and barometric pressure, and convert to the volume at and 760 mm. (see p. 43). To make the calculation divide 22,400 (22.4 L.) by the number of cubic centimeters of air displaced, and multiply this quotient by the weight of the chloroform vaporized; the product gives the weight of a gram-molecule of the sub- stance, and the same figures express the molecular weight. THE NATURE OF SOLUTIONS. OSMOTIC PRESSURE In their physical properties solutions are very different from gases. In attempting to apply gas laws to substances in solution, it is evident that other methods than those used in the case of gases must be adopted to measure the pressure of the dis- solved substance. We measure the pressure of a OSMOTIC PRESSURE 47 gas by means of a manometer, but it is ob- viously impossible to measure the pressure of a dissolved substance by the same means, for the only pressure which the manometer can record is that of the solution against the walls of its con- tainer. By making use of membranes, however, much can be learned about the behavior of solutions. If a permeable membrane, for example, parchment paper, is arranged as a partition to separate a solu- tion of some substance from pure solvent, the two liquids refuse to remain separate. The solvent passes through the membrane in both directions; but a more important fact is that the dissolved substance diffuses through the membrane into what was at the start pure solvent, and this process con- tinues until the liquids on both sides of the membrane become solutions of the same concentration. The energy manifested in this process of dialysis is diffusion pressure. If, however, a much less permeable membrane is used, diffusion of a solute through it is prevented; but the solvent readily passes through in both directions. Such a membrane is called a semi- permeable membrane. In a properly constructed apparatus this membrane can be used to demon- strate a kind of pressure different from diffusion pressure. The best example of a semi-permeable membrane is a film of copper ferrocyanide. Since this film of copper ferrocyanide is too fragile to exist un- supported, it may be deposited in the pores of a 48 ORGANIC CHEMISTRY porous cell (such as is used for electric batteries), and the following method may be used in prepar- ing it. A fine-grained porous cell, about four inches long and one inch inside diameter, is closed with a perforated rubber stopper, through which passes a glass tube connecting with a suction-pump. The cell is set in water, and the water is sucked through the pores; then placed in acid, then in water again. By this means the pores of the cell are thoroughly cleaned, and air is removed. When clean, the cell is placed in a concentrated solu- tion of copper sulphate, and suction is maintained until the pores are completely filled. The inside and the outside of the cell are then thoroughly washed with distilled water, after which it is filled with 3% potassium ferrocyanide solution and the outside is exposed to a solution of copper sulphate. The copper sulphate reacts with the potassium ferrocyanide in the pores of the porous pot, so that a fine gelatinous precipitate of copper ferrocyanide is deposited. After standing for a day the cell is washed in water. If a solution of cane sugar is placed inside and the cell is suspended in water, water will pass into the cell and cause the volume of fluid in this to increase so that, by connecting a vertical glass tube with the cell by means of a rubber stopper, fluid will mount up in it to a very considerable height. If, however, the liquid in the cell is put under pressure, increase in the volume of the solution is prevented. When the system is in equilibrium because the OSMOTIC PRESSUEE 49 pressure is so regulated as to prevent change in volume, exactly as much solvent diffuses out as diffuses in. By connecting a manometer with the apparatus, the pressure can be determined by measuring the height of the column of mercury. Large pressures are reported as at- mospheres pressure, 760 mm. of mercury constituting one atmosphere. The pressure thus demonstrated is called osmotic pressure. No membrane has ever been prepared that is absolutely semi-permeable, that is, im- permeable to all solutes. A carefully prepared membrane is truly semi-permeable to sugar solutions and to col- loidal solutions. The law of osmotic pressure as stated by van't Hoff and modified by Morse, is as fol- lows: The osmotic pressure of a substance in dilute solu- tion is the same amount of pressure that the substance would exert, if it could exist in the form of a gas at the same tempera- ture as the solution, and if it were confined to the same volume as that occupied by the pure solvent. If this law could be applied to concentrated solutions, it would mean that the osmotic pressure FIG. 16. 50 ORGANIC CHEMISTRY of all weight-normal 1 solutions at must be 22.4 atmospheres, 2 because this is the pressure of a gram-molecule of gas when compressed to the volume of a liter. On the basis of this, we can calculate what the pressure of any dissolved sub- stance in solution will be. Thus, the pressure x of a 1% solution of cane sugar may be calculated from the proportion: Molecular solution : 1% solution:: 22. 4 atmospheres :#. Solutions which obey the laws of osmotic pressure most accurately are those that are not more concentrated than one- tenth gram-molecular. Since a comparison has been made of osmotic pressure to gas pressure, it will be of interest to test the application of the gas laws to solutions. 1. According to Gay-Lussac's law, the osmotic pressure should be proportional to the absolute temperature. That this is so is proved by observa- tions like the following: A 1% solution of cane sugar at 14.2 has an osmotic pressure of 510 mm. Hg, and at 32 of 544 mm. Hg. According to calculation it should be 540.6 mm. Hg (practically agreeing with the finding), thus 1 By gram-molecular solution is meant the molecular weight of a substance in grams dissolved in an amount of solvent sufficient to make 1 L. of solution, while by weight normal is meant a solution in which the gram-molecular weight of sub- stance is dissolved in 1000 gm. of solvent. 2 The pressure should be 22.28 atmospheres according to Morse, because 1000 gm. of water at has a volume greater than 1000 c.c. OSMOTIC PRESSURE 51 2. According to Boyle's law, the osmotic pressure should be inversely proportional to the volume of the solution, or, in other words, directly propor- tional to the concentration. The osmotic pres- sures of glucose solutions of varying strengths (at the same temperature, 0), have been found to be as follows: Gram-molecules in Osmotic Pressure in 1000 gm. Water. Atmospheres. Observed. Calculated. 0.1 2.40 2.23 0.2 4.65 4.45 0.3 7.01 6.68 0.4 9.30 8.91 0.5 11.65 11.14 It will be noticed that the pressures observed are almost proportional to concentration. Thus the pressure for the 0.4 molar solution is twice that for the 0.2, but that for the 0.2 is not quite twice that for the 0.1. The figures given above as cal- culated pressures are the gas pressures which the glucose would be under if in the form of a gas at and confined to the same volume as the solvent. These values are a little lower than the actual osmotic pressure. Some would explain the variation as due to hydration of the sugar molecules. 3. According to Avogadro's hypothesis, all equi- molecular solutions (i.e., solutions in which the weights of the solutes in a given quantity of solu- tion bear the same ratio to one another as the molecular weights of those substances) ought to 52 ORGANIC CHEMISTRY have the same osmotic pressure. This has been found to be the case. Osmotic pressure is related to vapor pressure. When a substance is dissolved, the vapor pressure of the solvent is lowered. This lowering of vapor pressure explains why the freezing-point of a solu- tion is lower, and the boiling-point higher than that of the pure solvent. Increase of osmotic pressure is proportional to decrease of vapor pressure, so that the osmotic pressure of a solution has been cal- culated from its vapor pressure. This was found to agree closely with the pressure that was actually measured in an osmotic apparatus. The tendency of the pure solvent to diffuse through a membrane, so as to pass into the liquid having a lower vapor pressure, can be seen more clearly by considering the effect of a difference of vapor pressure in an experiment that does not involve the use of a membrane. Thus if pure water is put in one beaker and an aqueous solution in another, and both are set in a jar that is then tightly closed, vapor will pass off from the water, but will be taken up from the air of the jar by the liquid of lower vapor pressure, that is, by the solu- tion. The transfer of water from one beaker to the other is equivalent to distillation. If it were possible to subject the solution in the one beaker to pressure without at the same time cutting the liquid off from contact with the air of the jar, and also without changing the pressure on the pure water, the vapor pressure of the solution could be raised by the increasing hydrostatic pressure until OSMOTIC PRESSURE 53 finally it equaled that of the pure water; and In consequence distillation would cease. It will be seen, therefore, that pressure can be used to bring two liquids into equilibrium with each other as regards vapor pressure. It is not at all improbable that the equilibrium brought about in an osmotic apparatus by exerting pressure on the solution in the cup, is due to the establishing of an equilibrium of the vapor pressures of the two liquids. One of the recent theories as to the method of the passage of the solvent through the osmotic mem- brane supposes that the solvent is in the form of a vapor while passing through the capillary pores of the membrane. The vapor condenses, and is taken up by the solution on the other side of the membrane. According to this theory the pores do not become wet, and the process is simply distillation. If we accept this theory, we have no difficulty in understanding why the molecules of the dissolved substance do not diffuse through the pores of a perfect semi-permeable membrane. The old-time theory that the membrane acts as a sieve, preventing the molecules of the solute from passing through the pores, is no longer tenable. It has been recently shown that an osmotic mem- brane can be prepared by partially blocking the pores of an unglazed porcelain plate by means of a fine non-gelatinous precipitate. When the diam- eter of the capillaries has been reduced to about O.SM, the plate can be used to demonstrate osmotic pressure (but the pressure will be only a fraction of the true osmotic pressure of a solution). But 54 ORGANIC CHEMISTRY the diameter of these capillaries is from 500 to 1000 times the diameter of the molecules of most solutes, so that it is evident that there is no sieve- like action involved. A theory that is favored by some supposes that the solvent passes through the membrane by first .dissolving in the substance of the membrane and then passing out of the membrane on the other side. This theory does not take those membranes into account that are known to have capillary pores. By using a non-porous membrane, as, for example, a rubber membrane, and by using solvents that dis- solve in rubber, the osmotic pressure of solutions made with such solvents can be demonstrated. Such an experiment does not prove anything what- ever about the mode of action of a membrane in the case of aqueous solutions. It may well be true that osmosis occurs through some membranes in accordance with this solution theory; but the theory certainly does not apply to all membranes. Biological Methods for Measuring Osmotic Pressure. If, in the experiment with cane sugar solution, instead of placing the cell in water we had placed it in a solution of cane sugar weaker than that contained in the cell, then the osmotic pressure would not be so great as in the previous case, because water would pass into the cell only until the strength of the solution came to be the same as that outside it. This fact leads us to an important conclusion, viz.: that the relative strengths of two solutions can be ascertained by seeing whether osmosis oc- curs between them when they are separated from each other by a semi-permeable membrane. 1 1 This is true only for solutions of diffusible substances in the same solvent (water). OSMOTIC PRESSURE 55 In the case of the copper ferrocyanide cell above described, we could determine this fact by measuring the pressure inside the cell. If, however, we employed a closed sac of some semi- permeable membrane filled with one of the fluids, then we could, by suspending this sac in some other fluid, tell if osmosis had occurred, by seeing whether the sac became distended or the reverse. In the case of the red blood-corpuscles we have a structure analogous to this. The envelope of the cor- puscles acts like a semi-permeable membrane; it allows water to diffuse through it, but not salts. 1 Now a corpuscle contains a solution of salts and haemo- globin, and if it be placed in a fluid containing in solution the same number of molecules as is contained in the fluid inside the corpuscle, then no osmosis will occur in either direction and the corpuscle will remain unchanged in volume Such a fluid which is isosmotic with the fluid inside the corpuscle, is called an isotonic solution. If the corpuscle be placed in a solution which is weaker than that contained in the cor- puscle, then water will diffuse in and the corpuscle will distend and may ultimately burst. Such a solution is said to be hypo- tonic. If the corpuscle be placed in a solution which is stronger than that of its fluid contents, then water will diffuse out of the corpuscle, so that the corpuscle will shrink. Such a solution is called hypertonic. This change in the volume of the corpuscle may be observed under the microscope, and a quantitative expression also of the change in volume of the corpuscle may be obtained by using an instrument called a hsematocrit. This consists of a graduated narrow capillary tube, about seven centimeters long. At one end the tube is widened so as to give space in which the fluids may be mixed. Blood is drawn into the capillary by means of a syringe, and its volume accurately measured. The pipette is then closed at each end by small, 1 The corpuscles are, however, permeable for alcohols, free acids, and alkalies, ammonium salts, and urea. This explains why an isotonic NaCl solution remains isotonic after the addi- tion to it of urea, in spite of the increase in osmotic pressure. 56 ORGANIC CHEMISTRY accurately fitting, metal plates held in position by a spring. The tube is then placed horizontally in a rapid centrifuge and rotated so that the corpuscles are thrown to the outer end. The graduation mark at which the column of corpuscles stands is then noted. In another tube a drop of the same blood is mixed with an equal volume of the fluid the molecular concentration of which it is desired to determine. The exact amount of blood and fluid taken is read off from the graduations of the tube. The two fluids are then sucked into the wide part of the tube and mixed by means of a fine platinum wire. The tube is then closed and centrifuged. If the corpuscles stand at the same level as for blood alone, then we know that the solution is isotonic with the blood-corpuscles, which means that they must also be isotonic with the plasma. If the column of cor- puscles be longer, then we know that their volume must have been increased, and that the fluid under examination is hypo- tonic. If the column of corpuscles be shorter, the solution is hypertonic. Isosmotic solutions are isotonic to the same cells provided the cells are impermeable to the solutes. Solutions of corresponding concentration (as, one- tenth gram-molecular) of most organic compounds (except metallic salts, acids and bases) are isosmotic. Solutions of ionizable substances (p. 65) have a greater osmotic pressure than solutions of other substances, since each ion has the same effect as a molecule; a comparison is made in the following : Cane sugar (not ionized) 1 . 00 Potassium nitrate 1 . 67 Sodium chloride 1 . 69 Calcium chloride . . . . 2 . 40 OSMOTIC PPESSURE 57 These figures are the isotonic coefficients of the substances. The coefficient 1.69 for NaCl means that a 0.1 gram-molecular solution of salt has the same osmotic pressure as a 0.169 gram-molecular solution of sugar. In the case of living cells it seems to be necessary to take into account selective permeability; for example, the tadpole when immersed in a hyper- tonic sucrose solution (as 8%) shrinks noticeably in twenty-four hours, there being no injury to the epithelium; on the other hand, a tadpole placed in hypotonic sucrose solution (3%) does not swell up, because the epithelial cells are not noticeably permeable to water passing in. EXPERIMENTS. (1) Osmotic Pressure Effects in a Vegetable Membrane. With a sharp razor shave thin slices from a red beet, mount some on a slide, and examine microscopically. Now add a drop of saturated NaCl on the slice and observe that the red substance shrinks away from the wall of the cell, the hypertonic solution having caused plasmolysis. (2) Osmotic Pressure Shown by an Animal Membrane. The large end of an egg contains an air space, open the shell at this point, removing it down to where the egg membrane joins the shell. Cross three strips of parchment paper five inches long over the membrane, and stretch them on to the shell; bind them down to the shell beyond the middle of the egg with a rubber band, bend the strips back on themselves and hold them fast with another rubber band. Coat the bands with 58 ORGANIC CHEMISTRY melted paraffin to keep them in position. The parchment gives support to the membrane. To the opposite end of the egg attach a small upright glass tube by applying melted paraffin, run a long needle down the tube and carefully drill a hole through the shell and egg membrane; or the shell may be nicked before fastening the tube in position, and a wire can be put down the tube to break the egg membrane. Immerse the egg in distilled water. After standing some time the egg contents will have swollen sufficiently to force egg white up into the tube. (3) Osmotic Pressure Shown by an Inorganic Mem- brane, (a) Select a long narrow crystal of CuS04, tie a thread about the middle, and fasten the thread to a glass rod lying across the top of a small beaker so that the crystal hangs in potassium ferrocyanide solution. A copper ferrocyanide membrane forms, which becomes distended by the passage of water through it toward the copper sulphate. (6) Fill the bent portion of a U-tube with melted agar solution, cool, and when solidified fill one limb with CuS04 solution, the other with potassium ferrocyanide solution. On standing several days a sharply defined area of copper ferrocyanide forms midway in the agar. (c) Drop a small lump of CaC^ into a test-tube half filled with saturated potassium carbonate solution. On standing a membrane develops and grows, making plant-like forms. MOLECULAR WEIGHT DETERMINATION 59 MOLECULAR WEIGHT OF SUBSTANCES IN SOLUTION Theoretically, the measurement of the osmotic pressure would be a simple enough way of deter- mining the molecular weight, but, in practice, the method can seldom be used. Is there then no easily measurable physical property of solutions which depends on their molec- ular concentration, and which will, therefore, bear a relationship to the osmotic pressure? The vapor pressure of a solution is proportional to its osmotic pressure, but the method of determining vapor pressure is a difficult one to carry out. It has been found that the temperature at which a solvent freezes is lowered when a substance is dissolved in it, and that the amount of this lower- ing, or depression of freezing-point, 1 is for dilute solutions proportional, not, in general, to the chem- ical nature of the substance, but to the number of molecules of substance dissolved in a given volume. (The same holds true for the elevation of boiling- point, which can be most easily demonstrated with the McCoy apparatus. This method, however, will not be described here.) This being so, it follows that all gram-molecular solutions in the same solvent must lower the freezing-point to an equal extent. The depression of freezing-point pro- duced by a gram-molecular quantity of a sub- stance dissolved in 1000 gm. of the solvent (weight normal solution) varies for different sol- vents : 1 Cryoscopy is a name given to freezing-point determination. 60 ORGANIC CHEMISTRY Depression of Freezing-point. For water 1.86 " benzol 5.00 " phenol 7.20 '" acetic acid 3.90 These figures are called the constants 1 (or C) of the solvents. They correspond, therefore, to an osmotic pressure of 22.4 atmospheres. The osmotic pressure of solutions is commonly calculated from the depression of freezing-point. The apparatus in which the freezing-point de- terminations are made is known as Beckmann's. This consists of a large test-tube, to contain the substance, suspended in a somewhat larger test- tube, so as to form an air-jacket between the two tubes. The outer test-tube is placed in a freezing- mixture of iced water and salt contained in an earthenware jar (which has been wrapped round with flannel to diminish the heat-conduction). The freezing-mixture is stirred with a loop of wire as represented in the diagram. In the inner test- tube is suspended the bulb of a Beckmann ther- mometer. This thermometer does not give ab- solute readings of temperature as does an ordinary thermometer. It is used only for demonstrating the difference in temperature at which two solu- tions freeze, or with certain modifications it may 1 The constants are not always exactly those given above. Some substances give a depression of freezing-point of water, indicating a constant of 1.84 or 1.85. The constant for benzol seems to vary from 4.85 to 5.15. MOLECULAR WEIGHT DETERMINATION 61 be used to tell the different temperatures at which two solutions boil. Before the thermometer is used for freezing-point determinations, the menis- cus of the mercury column must be adjusted so that it stands within the scale -(high up) at the tempera- ture at which the solvent used freezes or crystallizes. To make this adjustment the bulb of the thermometer is placed in iced water ^ and if it be found that there is too much mercury to bring the meniscus within the scale, then the upper end of the thermometer is tapped with the fingers so as to cause the mer- cury at the top of the reservoir, which is connected with the upper end of the thermometer tube, to fall to the bottom and so to become disconnected from the mercury column in the thermometer tube. Should the meniscus of mercury stand be- low 3.5 on the scale at the FIG. 17. freezing-point of water, or of the other solvent used, then the thermometer must be inverted, and, by tapping, more mercury can be added to that in the tube. For making the actual freezing-point determina- tion the inner tube of the apparatus is partly filled with the solution under examination so that the latter comes a little above the bulb of the ther- 62 ORGANIC CHEMISTRY mometer (see Fig. 17). The tube is then placed directly in the freezing-mixture until the mercury, having fallen to its lowest level, begins to rise again, when the tube is removed quickly from the freezing-mixture and placed in the larger test- tube, as before described. The cooling is then proceeded with until the meniscus of mercury stands at a constant level.- During cooling, the fluid is kept constantly in motion by means of a platinum wire, bent into a loop as shown in the diagram. The reading is taken whenever constant and compared with the reading obtained when pure water (or whatever other solvent is used) is frozen. This difference is designated by A. 1 Since this constancy of (7, for any given solvent, is the point on which the method depends, the following experiment should be performed to demonstrate that for water C has the value given to it above. EXPERIMENT. Weigh out a quantity of pure dry urea corresponding to one-tenth its molecular weight in grams (i.e., 6 gm.); dissolve this in 100 1 Care should be taken that the supercooling is not excessive. If this be so, a correction is necessary because the formation of ice (pure water) lessens the volume of the solution, and there- fore, the depression is greater than it would be if only a trace of ice is present. For aqueous solutions 1.25% of A is added to the observed thermometer reading for each degree centigrade of supercooling, and by deducting from the freezing-point of water the true A is obtained. For example, suppose the freezing-point of water was at 3.9, that of the solution at 2, and the point of supercooling at 0. A is 1.9, then 1.9(2 x .0125) = .047, 2 +.047 =2.047; 3.9 -2.047 = 1.853= corrected A. MOLECULAR WEIGHT DETERMINATION 63 gm. of distilled water. Compare the freezing- point of this solution, corrected for supercooling, with that of pure water. Does it correspond to the constant? Also calculate the molecular weight of urea. In determining the molecular weight of any substance we must first of all choose the most suitable solvent for it, and, in an accurately weighed quantity of this dissolve an accurately weighed quantity of the substance under examina- tion. Knowing what C for our solvent is, in other words, through how many degrees centi- grade the freezing-point of our solution would be lowered were a gram-molecular quantity per 1000 gm. of solvent taken, if we find the freezing- point actually lowered to a less extent than this, we know that less than a gram-molecule must have been dissolved, the actual amount less than this being proportional to the difference from C recorded by the thermometer. In other words, the depression observed, represented by A, is to C as the strength of the solution . /weight of substanceX . - used I - - ) is to that of a gram- \ weight of solvent / molecular solution (or rather a solution containing a gram-molecule dissolved in 1000 gm. of solvent). S> C 1 m=X, where S equals the weight of sub- L A stance used in grams; L, the weight of solvent in S grams. , when solved, gives a decimal fraction 64 ORGANIC CHEMISTRY expressing what part of 1 gm. of the substance is dissolved in 1 gm. of solvent; therefore, to cal- culate the gram-molecule (the amount dissolved in 1000 gm. of solvent), ra must be multiplied by 1000, and M equals the molecular weight in the S C equation M - X XlOOO. For example, the A L A of a 1% cane-sugar solution is about 0.054. The molecular weight of the sugar, therefore, is 1 1 QA X XlOOO =344. According to the formula Ci2H 22 Oii, it should be 342. The A of blood and of urine are sometimes determined. That of human blood is about 0.55. In case of drowning the blood is diluted, therefore the A is much less; if a person were killed before being thrown into the water, the A would not be lessened. IONIZATION The method is not, however, applicable to all substances, even though they be readily soluble in the above-mentioned solvents. Weight normal solutions of certain substances give a depression of freezing-point greater than C. Practically all metallic salts and most acids and bases when in aqueous solution are included in this category. To demonstrate this let us determine the depres- sion of freezing-point produced by a gram-molecular solution of sodium chloride. EXPERIMENT. Weigh out one-tenth (one- twentieth is better) the molecular weight of pure sodium chloride in grams and dissolve, as in the IONIZATION 65 case of urea, in 100 c.c. of pure distilled water. Determine the depression of the freezing-point in Beckmann's apparatus. It will be found to be considerably greater than 1.86 (viz., about 3.35). Knowing that 1.86 is A for a gram-molecular solution, it is easy to calculate how many gram- molecules per liter (X) a A of 3.35 will represent, thus: 1.86 : 1::3.35 : X] X = 1.8. To ascertain the actual osmotic pressure of the sodium chloride solution we must accordingly multiply 22.4 atmospheres by 1.8. This gives us about 40 atmospheres. What then is the cause of this deviation from the law? The answer to the question is furnished by comparing the electrical conductivities of the two classes of solutions. Solutions of those substances which obey the above law will be found to be bad conductors of electricity non-electrolytes whereas solutions of those substances which do not obey it will be found to be good conductors electrolytes. This discovery, viz., that solutions which con- duct electricity appear, from the determination of A, to have a greater number of molecules than those which do not conduct, has led chemists to the conclusion that certain of the molecules in such solutions must split up into smaller parts, called ions, and that it is only when this dissocia- tion of molecules into ions takes place that it is possible for the solution to conduct electricity. 66 ORGANIC CHEMISTRY In fact, our whole conception of the conduction of electricity in solutions is based on this hypothe- sis. It is supposed that every molecule of substance is charged with positive and negative electricity, which in the intact molecules so neutralize each other that we do not appreciate either. When these molecules are suspended in solution, how- ever, they show a greater or less tendency to split up into ions, one set of which carries positive elec- tricity and the other negative electricity. These ions wander about the solution much as if they were independent molecules. Each ion has as much effect as a molecule on the vapor pressure, osmotic pressure and depression of freezing-point of a solution. When an electrical current is passed through a solution that has undergone dissociation into ions, the ions tend to collect at the two poles and yield up their electrical charges. Those which collect around the positive element or anode are. called anions, and those collecting around the negative element or cathode are called cations. Anions are charged with negative electricity, and cations with positive electricity. Examples of anions are OH and the acid portion of salts, for example 864, Cl, etc.; the cations include hydro- gen and metals. The ionization is not dependent on the passage of an electrical current. EXPERIMENT. Put some strong NaCl solution in a beaker, add a few drops of phenolphthalein solution, and immerse in the liquid a pair of battery ION I Z AT ION 67 plates, consisting of a strip of sheet zinc and one of copper soldered together at one end and separated in the liquid. As the electric current passes, sodium ions travel to the copper plate and give up their electric charges, becoming metallic sodium, which attacks the water and forms NaOH in the region of the copper plate, therefore a pink zone (OH ions) appears at this point. When solutions of acids undergo ionization, the cation H is that which confers the acidic properties on the solution. An un-ionized acid does not act like an acid; for example, EbSCU dissolved in toluene does not ionize and will not give off hydrogen in the presence of zinc. (Also see experiment under Picric Acid, p. 342). On the other hand, hydrogen itself, as the gas or in solution, shows no acid properties. We must assume, therefore, that the hydrogen ion is something different from the hydrogen atom. The same is true for other ions: they are not the same as the free elements or groups of elements; they are particles with opposite electrical charges which behave like molecules. It is believed that the ions are hydrated, i.e., that they hold molecules of water intimately attached to them. It is usual to designate the various ions by their symbols, affixed to which is the sign * for cations (e.g., H', Na", etc.) and ' for anions (e.g., Cl', NO'a etc.). Some ions, however, must carry two or more units of electrical charge, for otherwise in the case of such a substance as H 2 S04 there would be an excess of positive electricity in the molecule. 68 ORGANIC CHEMISTRY The ion S(>4 must therefore carry two charges of negative electricity and be represented by the sign SO r/ 4. The valence of the ion usually agrees with the number of unit charges of electricity that it carries. The coefficient of dissociation therefore indicates what proportion of the molecules have become split up into ions. For molecules that can yield only two ions it cannot be greater than 2, but for those splitting into more than two ions it may exceed this number. In the concentration of a 1% solu- tion KC1 has a coefficient of 1.82, KN0 3 1.67, K 2 S0 4 2.11, Na 2 C0 3 2.18 and NaCl 1.9. The amount of dissociation that a salt or acid undergoes in solution depends very largely upon the dilution: the greater the dilution, the greater the dissociation. 1 EXPERIMENT. To 1 c.c. of a saturated solution of cupric bromide add water gradually 5 drops at a time, and note the color changes. When the color is a pure blue, determine whether it is exactly the same color as that obtained by diluting solutions of cupric sulphate, nitrate and acetate. What is the blue color due to? In a solution of an electrolyte there is a condition of equilibrium between molecules and ions. The molecules are continually dissociating, and simul- taneously ions are uniting to form molecules. Re- 1 For example, HC1 is completely dissociated. IONIZATION 69 actions between electrolytes proceed rapidly, be- cause as fast as ions are used up more molecules ionize in the effort to restore equilibrium. Even the trace of H and OH ions present in pure water (H ions amounting only to 0.0000001 gm. H per L at 22) facilitates chemical reactions. Most organic com- pounds react slowly because of absence of ions. EXPERIMENT. To two test-tubes add a few c.c. AgNOs ; to one add NaBr, and to the other Occasionally, when a substance is dissolved, in- stead of dissociation there occurs a fusion or associ- ation of several of the molecules. In such a case the freezing-point or boiling-point method would give too high a molecular weight. This tendency to form complex molecules most frequently mani- fests itself when the organic substances contain hydroxyl or cyanogen groups, and when chloroform or benzol is used as the solvent. For example, an 8% solution of phenol in benzol gives a depression of freezing-point indicating a molecular weight of 188, which is twice that called for by the formula, C 6 H 5 OH. Many liquids polymerize, that is, their molecules associate. The condition of water is supposed to be represented by (H 2 O) 4 . 2 Liquid hydrocyanic acid is (HCN)e. Next in order of association are formic acid and methyl alcohol. The greater the polym- 2 H 2 0, (H 2 0) 2 , and (H 2 0) 3 are also present. Some chemists think that liquid water is a mixture of these three (but mainly dihydrol), and that ice is trihydrol, while steam is monohydrol, 70 ORGANIC CHEMISTRY erization of the solvent, the greater will be the dissociation of an electrolyte. EXPERIMENT. Add a few drops of phenol- phthalein solution to 25 c.c. of neutral ethyl alcohol, then one drop of concentrated NH 4 OH; there is no color change. Dilute with water, and a pink color develops because ionization of the hydroxide takes place in the dilute alcohol. HYDROLYTIC DISSOCIATION Many salts when dissolved in water, undergo not only electrolytic dissociation, but also hydrolytic dissociation. The latter is induced by the action of water. Three classes of salts are hydrolyzed: 1. Salts formed by the combination of a weak base with a strong acid. The hydrolysis is illustrated in the following equation: FeCl 3 +HOH = FeCl 2 OH + (H + Cl) . 2. Salts formed from a strong base and a weak acid: KCN+HOH = (K+OH)+HCN. 3. Salts formed from a weak base and a weak acid : CH 3 COONH 4 +HOH = NEUOH +CH 3 COOH, The condition of the solutions is not fully repre- sented by the above equations, because only a cer- tain fraction of the solute is hydrolyzed in each SURFACE TENSION 71 case. In a one-thirtieth gram-molecular solution of aniline hydrochloride about 2.6% of the molecules are hydrolyzed to aniline and hydrochloric acid. A solution of a salt of class 1 is acid in reaction because of the ionization'of the strong acid set free (while the basic product of hydrolysis furnishes but few OH ions). A solution of a salt of class 2 is alkaline because the strong base liberated yields so many OH ions, but the weak acid hardly ionizes at all. A solution of a salt of class 3 will be neutral if both base and acid are equally weak, because the effect of the few H ions from the acid is neutralized by that of the correspondingly few OH ions from the base. EXPERIMENT. Dissolve a little potassium citrate in 1 c.c. of distilled water. In similar manner pre- pare a solution of phenylhydrazine hydrochloride. Test each with litmus paper. SURFACE TENSION The molecules of a liquid are attracted to one an- other in all directions, these attractions neutraliz- ing one another. At the surface, however, the molecules are attracted by the molecules below and at the sides, but as there is no counterbalancing attraction above there results a definite pressure called surface tension. The pressure crowds the molecules closer together. Surface tension is equiv- alent, then, to the stretching of an elastic mem- brane at the surface. Fine powders of such a nature that they do not readily take up moisture (as 72 ORGANIC CHEMISTRY sulphur) float when sprinkled on water; the par- ticles rest on the surface exactly the same as if on a membrane. If the surface tension is lowered, as results when bile salts are dissolved in the water, such particles will not be buoyed up, but will sink. Surface tension is manifested also wherever the liquid comes in contact with the supporting vessel. The effect of surface tension is very noticeable in the case of small amounts of liquid under cer- tain circumstances. If a little water is dropped on an oily or paraffined surface, it will not spread out in a film, but will gather together into drops. The small drops are almost spherical, while the large drops are flattened. Surface tension causes the liquid to assume the form that has the least surface, that is, the spherical. Unless the drop is very small, the pull of gravity will modify the effect of surface tension. When a drop forms at the tip of a pipette, it appears to be exactly spherical while small, but as it grows in size it assumes a some- what bag-like shape. The drop falls when its weight becomes great enough to overcome the tension which has been holding it suspended. The surface tension of a liquid may be determined by finding the weight of the drops delivered from a stalagmometer. For accurate estimations the tip of the instrument must be of a certain diameter and must have been standardized; also the drops must form slowly and have a typical shape. A correction must be made for temperature. Or- dinarily it suffices to count the number of drops SURFACE TENSION 73 produced by emptying a stalagmometer, and to compare with the number of drops of water delivered from the instrument at the same temperature. Allowance must be made for the density of the liquid. The formula for the calculation of the sur- face tension as dynes is as follows: Dynes per Number of drops of water cm.= T-r- -TT: X specific gravity Number of drops of liquid X73. The factor 73 is the surface tension of pure water in dynes, determined for a line at the surface of the water one centimeter in length. Capillarity is due to surface tension. If a glass plate is suspended in water, the liquid will wet the glass for some distance above the surface of the water. This amounts to an increase in the total surface. But the force of surface tension combats an increase in surface, and tends to pull the surface into the least possible area. This it does by raising water at the junction of the surface with the glass, so that the surface curves upward on to the glass. The area of the surface along this curved portion is much less than the area of the surface in this region if it could lay flat plus the area of the vertical film of water on the glass plate. The weight of water raised is dependent on the length of contact of the water with the glass. The curved portion of the surface is called the meniscus. If a number of glass tubes of different internal diameters are placed in water, the effect of capil- larity seems to be different in the various tubes. 74 ORGANIC CHEMISTRY In a wide tube there is only the formation of a meniscus; this is exactly the same effect as with the glass plate, the only difference being in the curve of the glass wall. In a narrower tube the water is raised slightly, because the amount of water en- closed in the tube is greatly diminished in propor- tion to the number of vertical lines of contact, and there will not be a sufficient weight of water in a meniscus to balance the pull, therefore, a column of water must be raised to get the requisite weight. In the case of a tube having a capillary bore the amount of water available for the action of each line of contact is extremely small, and in con- sequence the water is raised to a considerable height. The relative surface tension of a liquid may be determined by measuring the height of the column of liquid in a capillary tube, and comparing with the height of the column of water when the same tube is used in water. The reading must be corrected for the specific gravity of the liquid, so that the comparison made will be of weights of liquids raised. The absolute surface tension can be calculated, if the diameter of the capillary is known. Many organic liquids, such as methyl and ethyl alcohols, ether, chloroform, glycerol, acetone, aniline, pyri- dine, phenol and certain organic acids, have a low surface tension; on the other hand when they are dissolved in water they lower the surface tension of the water. -~* EXPERIMENTS. (1) Fill a test-tube with water, and another with 0.1% solution of castile soap; on SURFACE TENSION 75 the surface of each liquid dust a few very fine par- ticles of sulphur. The sulphur sinks in the soap solution. Dilutions of the soap may be made to find how dilute a solution still shows marked lower- ing of surface tension. 2. Place a little paraffin on a small glass plate, and melt it by warming over a flame, so that a smooth layer is obtained. Attempt to spread water as a film over the paraffin. Observe the shape of small and of large drops of water that stand on the paraffin. 3. Pour about 10 c.c. of saturated K 2 COs into a test-tube, and add a few drops of chloroform. Notice that the latter forms a layer on the car- bonate. Hold the test-tube obliquely, and pour down the wall about 5 c.c. of water, but do not mix the liquids. Why does the chloroform refuse to remain as a layer between the two aqueous liquids? 4. Count the drops delivered from a stalag- mometer, using (in the order indicated) ether, chloroform, alcohol and water. Use suction to dry the tube before each filling. A 1 or 2 c.c pipette having a fine tip may be substituted for the stalagmometer, if necessary. In order to secure slow dropping, attach a piece of rubber tubing, and use a pinchcock to control the outflow. Do not handle the glass parts after filling; and keep the apparatus in a vertical position (since the size of the drops may be different if held in an inclined position). Calculate the surface tension of each liquid by means of the formula given above. 76 ORGANIC CHEMISTRY 5. Compare the relative surface tensions of ether, chloroform, alcohol, and water, after having meas- ured the height of the column of liquid raised in a graduated capillary tube of medium-sized bore. After using the tube in one liquid dry it by suction before placing it in another. Before comparing the results multiply each reading by the specific gravity of the liquid. The surface of the liquid is that part in contact with the air; this may be called the air-liquid inter- face. As a matter of fact there are other surfaces. For instance, wherever the liquid comes in contact with the supporting vessel there is a surface, a solid-liquid interface. Also, if particles are sus- pended in the liquid, there is a solid-liquid interface about each particle. A liquid-liquid interface ex- ists at the plane of contact of two immiscible liquids. If hydrated particles of substance in the liquid phase (emulsoid colloids, see p. 81) are present in suspension in water, there is a liquid- liquid interface about each particle. Surface tension is not the same, quantitatively, at these various interfaces. It is stated that the surface tension at the solid-liquid interface is much greater than that at the air-liquid interface, while it is least at a liquid-liquid interface. Sur- face tension effects are of considerable importance in the case of colloidal particles. Inorganic salts raise the surface tension of the water in which they are dissolved, while most dissolved substances lower it. At liquid-liquid VISCOSITY 77 interfaces, however, all substances (including salts) lower the surface tension of the solvent. Gases are more soluble in liquids of low surface tension, and the degree of solubility is almost pro- portional (inversely) to. the surface tension. For example, the solubility at of C02 in 1 c.c. of water, alcohol, and ether is 1.713, 4.33, and 7.33 c.c. respectively, while the surface tensions of these liquids are 73, 22 and 16 dynes. VISCOSITY The viscosity of a liquid depends upon its inter- nal friction. The friction is due to the adhesion of the molecules of the liquid to one another. A measurement of this friction may be made by observing the time required for a certain quantity of liquid to pass through a capillary tube and com- paring with the time required by an equal volume of water in the same apparatus. In the calculation account must be taken of the specific gravity of the liquid, because increase in the weight of the column of liquid increases the pressure and, there- fore, increases the rate of flow. We may suppose that the layer of liquid in con- tact with the wall is not moving, that the next layer is moving slowly, and that each layer moves faster the nearer it is to the center of the tube. The rate of flow of the liquid as a whole will depend upon the amount of friction between these successive layers, hence measurement of this rate gives a basis for calculating viscosity. When liquid particles push past one another in this way, work must be done, 78 ORGANIC CHEMISTRY and the amount of work necessary is dependent upon the internal friction. Specific viscosity is the ratio of the viscosity of a liquid to that of another liquid that has been chosen as a standard. For example, compared with water as unity, the specific viscosity (at 25) of 5% ethyl alcohol is 1.161, and of 5% ethyl acetate is 1.044. It will not be necessary to discuss the determina- tion of the absolute viscosity of a liquid. The temperature of the liquid must be controlled when its viscosity is determined, since increase in temperature diminishes viscosity. The tempera- ture should always be reported. The coefficients for change in viscosity for temperature are different for different liquids. The viscosity of organic liquids belonging to an homologous series (see p. 104) increases in pro- portion to the increase in molecular weight. The viscosity of the blood is of great physiological importance. Fluidity is the reciprocal of viscosity. In proportion as the viscosity is lessened, the fluidity is increased. EXPERIMENTS. (1) Compare the viscosity of water, and of absolute alcohol in an Ostwald vis- cosity pipette. To do this pour about 5 c.c. of the liquid into the large tube and by suction from a suction-pump draw it into the small tube and bulb, filling above the upper mark; disconnect and prevent the liquid flowing back by sealing the end with the finger (as in using a pipette); draw off the excess of liquid in the large tube with a pipette. COLLOIDS 79 Now releasing the finger start a stop-watch at the instant that the meniscus reaches the upper mark and stop the watch when it reaches the mark on the capillary tube. 2. Use a viscosimetex- such as is used for com- mercial chemical work; Scott's is a simple apparatus. Try this with water and later with an oil at the same temperature (preferably at 20). Each determina- tion is made as follows: put 200 c.c. of the liquid into the viscosity cup, set a graduate under the cup to catch the outflow, press the lever which raises the plunger and at the same instant start the watch; when 50 c.c. has flowed out stop the watch and let the plunger fall. Dividing the time for the oil by the time for water gives the figure for the viscosity number 1 of the oil. Now raise the temperature of the oil 20 and make another determination. COLLOIDS Dispersion of Substances in a Liquid. When sodium chloride dissolves in water, it forms what we call a true solution. The molecules of NaCl, and also the Na and Cl ions are uniformly dis- tributed throughout the mass of the solvent. In In test' "le oil for iter^ti-m v ocurel 137 acternlnlr . ">iuc- ed fro ail The Ostviald v tic - rfc of exnctly Gher , r xlc . ) 80 ORGANIC CHEMISTRY the solution there is both ionic and molecular dis- persion. In a true solution of a substance that does not ionize there is only molecular dispersion of the substance. On shaking an insoluble powder (as talcum) with water the fine particles are scattered all through the liquid, and seem to be in uniform suspension. This condition is temporary, however, for, on standing, the liquid becomes clear and all of the solid sub- stance is deposited at the bottom. In the case of some substances the particles may be fine enough to remain suspended for a long time. Such a mix- ture is a suspension, not a solution. Insoluble liquids may be broken by shaking with water into minute droplets. As long as these drops remain suspended the mixture is an emul- sion. In order to form a permanent emulsion it is generally necessary to use an emulsifying agent. This forms a film about the drop, so that it is kept separate from other drops. In cream the fat is present as a permanent emulsion, the microscopic drops being enclosed by films. Intermediate between these coarse dispersions of solids and liquids in liquids, and the molecular dispersions of true solutions, there is another type of dispersion that is characteristic of colloidal solu- tions. The particles in a colloidal solution are larger than the largest molecules in a true solution, but smaller than the smallest particles in a suspen- sion or emulsion. The colloidal particles remain permanently suspended. Some colloidal solutions are somewhat opaque or opalescent, but others are COLLOIDS 81 practically as clear as true solutions. One of the distinguishing differences between colloidal solu- tions and true solutions is the fact that in all colloidal solutions the particles have surfaces of contact with the liquid, while in true- solutions there are no sur- faces of contact of the dissolved substance. These surfaces are an important factor in the behavior of colloids. There are two kinds of colloids, suspensoids and emulsoids. Suspensoid particles are in the solid phase, while emulsoid particles are in the liquid phase. Suspensions and suspensoids are essentially of the same nature, differing only in the size of the particles. In appearance, however, they are dis- tinctly different, since suspensions are invariably turbid, but suspensoid solutions may be quite clear, so that they seem to be free of solid particles. Emulsions and emulsoids are not of the same nature, although both consist of liquid particles suspended in liquids. The liquid particles in an emulsion are practically insoluble, and have no affinity for the liquid in which they are dispersed. Emulsoids, however, readily take up the solvent, so that the particles become liquid particles. The solvent dissolves in the colloidal substance, and the latter, instead of becoming molecularly dispersed, breaks up into infinitely small liquid particles. In the case of colloidal solutions in water we may say that the emulsoid particles are hydrated. Suspensions, emulsions, and colloidal solutions are heterogeneous mixtures, while true solutions are homogeneous. 82 ORGANIC CHEMISTRY In the following classification of dispersion mix- tures the diameter of the particles is indicated. HOMOGENEOUS DISPERSIONS Ionic dispersions Molecular dispersions . 1-1 . MM 1 MICRO-HETEROGENEOUS DISPERSIONS Emulsoids 1.0-100 MM Suspensoids 1.0-1 00 MM COARSE HETEROGENEOUS DISPERSIONS Emulsions greater than 100 MM Suspensions greater than 100 MM We must warn against getting the idea that these forms of dispersion are rigidly separated from one another. It is believed that all substances can be brought into colloidal solution under proper con- ditions. Therefore, it is better to throw the em- phasis on the colloidal state, and to avoid looking upon certain particular substances as distinctively colloidal. A true solution may spontaneously change to a colloidal solution. Thus, silicic acid, when first prepared, is in true solution, and on standing be- comes mainly colloidal, finally changing to a typical colloidal gel (see p. 84). In some cases there may be a trace of substance in true solution, in equili- brium with that portion which is in colloidal solu- tion. It is supposed that, if a substance has extremely large molecules, a molecularly dispersed 1 A MM is one-millionth part of a millimeter. COLLOIDS 83 solution of it may have the properties of a colloidal solution. For instance, haemoglobin is considered by some to have single molecules as the ultimate particles in solution, yet it is colloidal. As a rule, however, the very smallest particles in a suspensoid or emulsoid solution are clusters or aggregations of many molecules. Behavior of Colloidal Solutions. Solutions of sus- pensoids do not gelatinize, are not viscid, and are coagulated by a small quantity of electrolytes. They are irreversible colloids, that is, after being evaporated the residue cannot be put into colloidal solution again. The surface tension of these solu- tions is practically the same as that of the pure solvent. EXPERIMENT. Prepare colloidal Prussian blue as follows: measure into one test-tube 10 c.c. N/50 ferric chloride, into another 10 c.c. N/50 potassium ferrocyanide, and pour the two solutions simultaneously at the same rate into a clean beaker. A blue solution free of precipitate is secured. Shake some of the solution in a test-tube; it does not form a foam, there is no evidence of viscidity. Dilute about 5 c.c. with 25 c.c. of distilled water; there is no precipitate. To 5 c.c. of the diluted solution add 5 c.c. of magnesium chloride solution. On standing a blue precipitate forms. Save the more concentrated Prussian blue solution for a later experiment. To test reversibility evaporate 5 c.c. in an evaporating dish on the water-bath, and attempt to redissolve the residue. 84 ORGANIC CHEMISTRY Illustrations of suspensions are: colloidal gold, colloidal hydroxides of metals (as Fe(OH)3), and colloidal sulphides of metals (as As 2 S 3 ). Emulsoid solutions are viscid, they tend to gelatin- ize, and they are not coagulated by small amounts of electrolytes. After evaporation the residue can be redissolved, so that they are reversible. They are also reversibly soluble after precipitation by alcohol or certain salts. Emulsoid solutions usually have a lower surface tension than the pure solvent. EXPERIMENT. Pour about 5 c.c. of warm 5% gelatin solution into a test-tube. Shake well, the frothing indicates viscidity. Cool the tube with running tap water; the solution becomes a jelly. Warm the tube until the gelatin liquefies; pour part of it into an evaporating dish and evaporate to dryness on a water-bath; to the rest add an equal volume of magnesium chloride solution. Dissolve the residue in the evaporating dish with hot water. To a few c.c. of dilute gelatin solution add ammonium sulphate crystals, and shake. Filter off the pre- cipitated gelatin, and dissolve it in hot water. Illustrations of emulsoids are: silicic acid, tannin, soaps, many of the dyes, gelatin, albumin and other proteins. A colloidal solution when in the liquid condition is called a sol, and when in the gelatinized state a gel. If the solvent is water the terms hydrosol and hydrogel may be used. When a solution " gelates," a structure or framework develops in the liquid. In some cases the structure is sponge-like, liquid COLLOIDS 85 being interspersed throughout. In other cases (e.g., 13% gelatin) the liquid is held as separate droplets imprisoned in the solid gel substance. Diffusion of Colloids. The rate of diffusion of typical colloids is only one-hundredth of that of the most rapidly diffusing electrolytes, and about one-tenth of that of cane sugar. Diffusion may be tested by bringing the solution and solvent to- gether, but separated by an easily permeable membrane. Crystalloids diffuse into soft colloidal gels, passing along the liquid pathways of the gel almost as readily as they diffuse in a liquid. Col- loids, however, diffuse very slowly into gels. EXPERIMENT. Take two test-tubes containing 1% agar-agar solution in the gel state. Into one pour Prussian blue solution; into the other pour some ammoniacal copper hydroxide solution (to 5 c.c. concentrated copper sulphate solution add ammonia water until the precipitate is just redis- solved). Let the tubes stand an hour or more; the Cu solution penetrates the agar, while the col- loidal suspension does not. At the end of the session empty the tubes, leaving the agar in, rinse out; and note the condition of the agar. In which tube is agar colored blue? Dialysis. Colloids will not diffuse through a gelatinous partition such as an animal membrane or parchment paper, but crystalloids pass through it quickly. Certain colloids are said to dialyze to a slight extent. It may be that in these cases there is a trace of the substance in true solution main- 86 ORGANIC CHEMISTRY tained in equilibrium with the colloidally dissolved substance; then it would be expected that more of the colloidal substance would go into .true solution as fast as the molecularly dispersed part passes through the dialyzer membrane, so that slow continuous dialysis would take place. Ultra-filtration. By impregnating pieces of filter- paper with gelatin of different concentrations from 2 to 10%, and then hardening the gel by exposure to formaldehyde, filter disks can be obtained in which there is a gradation in the size of the pores. The 10% gelatin produces a filter having the small- est size pores; this filter holds back almost all colloidal particles. Working with a set of these filters, results are obtained that enable one to arrange a list of colloidal solutions in the order of the size of their particles. In the following list Prussian blue has the largest, and dextrin the smallest particles Prussian blue. Colloidal ferric hydroxide (about 44 /*/*). Casein (in milk). Collargol (about 20 MM). 1 per cent gelatin. 1 per cent haemoglobin. Serum albumin. Albumoses. Dextrin. As a rule suspensoid particles are much larger than emulsoid particles. COLLOIDS 87 Optical Properties. A microscope of the highest power (2250 magnifications) can detect a body 140 w in diameter. The particles in most sus- pensions and emulsions can, therefore, be seen. These microscopic particles have been named microns. Visual evidence of the existence of col- loidal aggregations in a solution can be obtained by using the ultramicroscope. A microscope is used, but the illumination is from one side instead of from below. An intense beam of light from an arc lamp is passed through a special condenser, so that it is focused to a point within the solution directly under the lens of the objective. The colloidal particles diffract the light, so that some rays pass up through the microscope. This diver- sion of light is on the same principle as the Tyndall phenomenon observed in the scattering of light by dust particles, when a sunbeam passes into a darkened room. The light is polarized. The par- ticles appear as dots or tiny specks of light on a dark background. Those that can be seen as separate points of light are called submicrons. In some solutions the particles are so small that they cannot be detected, but they cause a haze of light to be seen; these are called amicrons. The particles in colloidal solutions of metals have a greater power to diffract light than those in other colloidal solu- tions, so that particles of colloidal gold as small as 3-5 nfj. (about 10 times the size of alcohol and ether molecules) have been detected. In the case of emulsoids the particles exert so much weaker action in diffracting the light, that 88 ORGANIC CHEMISTRY they cannot be seen as submicrons unless their diameter is at least 30 /*/*. Most emulsoid solu- tions show a haze of light, and, therefore, have amicrons. Submicrons have been observed in al- bumin, gelatin, glycogen, and agar hydrosols. Diluting a solution may cause amicrons to take the place of submicrons. Heating some solutions (as 3% soluble starch or 0.01% gelatin) can change submicrons to amicrons. In the presence of elec- trolytes (or, in some cases, alcohol) the particles are aggregated into larger clumps, and appear large in the ultra-microscope. Motion of the Particles. Colloidal particles are constantly in motion (Brownian). Submicrons have been observed to trace a zigzag course. The motion of large particles is oscillatory. The premanency of suspension of the colloidal particles is largely due to their motion. Increase in the viscosity of a solution lessens Brownian movement. Surface Tension of Colloidal Solutions. Suspensions and suspensoid solutions have practically the same surface tension as the pure liquid. Emulsoids, however, affect the surface tension; some increase it (e.g., starch and gum arabic), and others lower it (e.g., dextrin, gelatin, egg albumin, tannic acid, fats, resins and soap). This difference in behavior can be taken advantage of for the purpose of dis- tinguishing emulsoids from suspensoids Venetian soap (olive oil soap) has a marked effect in high dilution, thus a 0.004% solution has a very low sur- face tension. The surface tension of emulsoid solutions is changed by H ions, OH ions, and by COLLOIDS 89 salts. Rise of temperature decreases surface ten- sion. Surface tension effects take place within all colloidal solutions, since there is a surface of the liquid presented to the surface of each particle in the solution. How important this is in a consideration of col- loidal solutions will be understood by noticing the enormous increase of surface exposure when a sub- stance is divided into fine particles. A compact sphere of substance one mm. in diameter (surface area of 0.0314 sq. cm.), if broken up into particles of uniform size, corresponding to the size of the larg- est suspensoid particles (O.lju), will acquire a sur- face area of 314 sq. cm. If a colloidal solution is purified, that is, freed of other dissolved substances, the surface tension about the particles becomes higher, and as it becomes higher, the difference in potential increases and the particles divide into smaller particles. Viscosity of Colloidal Solutions. Suspensoid solutions have a viscosity but slightly different from that of the pure solvent. A 3.85% solution of a colloidal silver compound was found to be only 1% more viscid than pure water. Some emulsoids (as agar- agar) show great viscosity in low concentrations. Most emulsoid solutions, if stronger than 1%, have increased viscosity. Traces of acid or of alkali increase the viscosity of some emulsoids. There is a point of maximum viscosity; for example, with gelatin solution the N maximum viscosity with HC1 is secured when 90 ORGANIC CHEMISTRY is present. The maximum viscosity with NaOH N is the same, but is obtained when is present. Increase of temperature lessens the viscosity. But in the case of albumin solutions a marked increase in viscosity has been observed at a temper- ature slightly below that at which heat coagulation occurs. ' Osmotic Pressure of Colloids. Osmotic pressure has been demonstrated with some colloidal solu- tions. Haemoglobin in 3% solution gave 12 mm. mercury pressure, and in 6% solution 22 mm. The osmotic pressure of 1.5% gelatin was found to be 8 mm., and that of 1.5% egg albumin was 25.6 mm. For these determinations a dialyzing mem- brane was used as the osmotic membrane, so that the effect of impurities was neutralized, since these dialyzed until there was exactly the same con- centration of them in the liquids on both sides of the membrane. Apparently the colloidal particle exerts the same effect in causing osmotic pressure as a molecule of a crystalloid. The number of molecules aggregated together into a colloidal agglomerate is variable and may be different at different times in the same solution. Whenever the colloidal clumps become larger the osmotic pressure is lessened. Molecular Weight of Colloids. The true molecular weight cannot be calculated from the osmotic pressure, because the number of molecules in the colloidal particle can not be determined. Exactly the same difficulty applies to molecular weight deter- COLLOIDS 91 mination by the freezing-point method. The read- ings for depression of freezing-point are too low to be made use of, since a solution which has an osmotic pressure of 50 mm. gives only 0.005 depression. In the case of haemoglobin the smallest possible molecular weight can be calculated from the con- tent of iron on the supposition that each molecule contains one atom of iron; but it does not necessarily follow that this minimum is the correct molecular weight. Electrical Charges of Colloids. The particles in a colloidal solution carry positive and negative charges of electricity; and, since the charges are all of the same kind, the particles repel one another. This repulsion is a factor of importance in main- taining the stability of a colloidal solution. When a current of electricity is passed through a colloidal solution, the particles travel to one electrode, to the cathode if they are electro-positive, but to the anode if they are electro-negative. This process is called cataphoresis or electrophoresis. The nature of the electrical charge is determined by this method. Most suspensoids are electro-negative, but a few (as the hydroxides) are electro-positive. Prac- tically all emulsoids that are of importance physio- logically are electro-negative. Haemoglobin, how- ever, is electro-positive. An albumin solution, that had been purified so as to free it of electrolytes to the highest degree, showed no cataphoresis; but when acid was added to the solution, the colloid became electro-positive (effect of H ions), and, when alkali was added, it became electro-negative 92 ORGANIC CHEMISTRY (effect of OH ions). Some favor the view that most emulsoids would be found to be electrically neutral, if sufficiently purified. In their natural environ- ment in vegetable and animal tissues, emulsoids would never be electrically neutral. Many of the dyes are emulsoids, some being electro-positive, and others electro-negative. Precipitation of Colloids. If two suspensoids of opposite electrical sign are mixed in such pro- portions that there are just as many positive as negative charges present in the mixtures, maxi- mum mutual precipitation occurs. The oppositely electrified particles attract each other, and when they meet the charges are neutralized. This change in electrical condition lowers the surface tension about the particles, so that larger colloidal clumps must necessarily be formed. The agglomeration of the colloidal masses progresses steadily until they are large enough to separate out as a precipitate. The Brownian movement aids in bringing the masses together after the factor of electrical repulsion has been eliminated. Emulsoids of opposite electrical sign can cause mutual precipitation. In this case, also, there must be the proper relative proportions of the two colloids. EXPERIMENT. To 1 or 2 c.c. of colloidal arsenious sulphide solution x add gradually, a drop at a time, 1 Arsenic sulphide may be prepared in colloidal solution by pouring a boiling hot saturated solution of arsenious acid into an equal volume of cold water that has been saturated with H 2 S. Continue the passage of the H 2 S until the mixture retains COLLOIDS 93 colloidal ferric hydroxide (Merck's dialyzed iron containing 5% Fe20s) ; let it stand a few minutes after each addition. Finally a decided precipitate will be obtained. It is difficult to regulate the pro- portions just right. Maximum precipitation is se- cured when the mixture contains 24 parts by weight of As2$3 and 13 parts of Fe20s. Precipitation by Salts. Suspensoids are precipitated by ions of opposite electrical sign; electro-positive colloids, as ferric hydroxide, are precipitated by anions, as Cl, SCU, while electro-negative colloids, as arsenious sulphide, are precipitated by cations, as H, K, Mg. The colloidal particles attract the ions carrying an opposite electrical charge; their electrical charges are thus neutralized. In conse- quence precipitation occurs for the reason explained above. The precipitating power is proportional to the concentration of the ions. Thus a 0.7 gram- molecular solution of acetic acid and a 0.0038 gram-molecular solution of hydrochloric acid have the same concentration of H ions, and have the same degree of precipitating action on colloidal arsenious sulphide. The precipitating ions are held by the colloidal masses (adsorption, see p. 95) while the other ions remain in solution. Emulsoids are not precipitated by small quanti- the odor of the gas after thorough shaking. Nowj*emove the free H 2 S by passing hydrogen through the solution. An opaque yellow liquid is secured. If there is any precipitate remove this with the aid of a centrifuge. 94 ORGANIC CHEMISTRY ties of electrolytes; the latter, however, have an effect on the solution. When an electrolyte is added to a solution, it concentrates at the inter- faces between the colloidal particles and the solvent, just as it does at the air-liquid interface. Salts lower surface tension at liquid-liquid interfaces (see p. 76); and, since the surface tension about the colloidal particles is lessened, the particles must come together to form larger clumps so as to restore the balance in potential. If an emulsoid solution, that shows only amicrons, is treated with an elec- trolyte, submicrons will be seen in it with the ultra-microscope. Addition of more electrolyte in- creases the size of the particles. Precipitation of emulsoids occurs when large amounts of very soluble salts are added; this is generally referred to as a salting-out process. The explanation offered is that such concentrations of salts act to abstract water from the hydrated col- loidal particles, so that the latter are reduced to the solid phase, and, therefore, become suspensoid particles, which are easily precipitated. In contact with water most insoluble substances acquire negative charges of electricity. For example, the fibers of filter-paper, wool, cotton and asbestos become electro-negative. This is true also of the particles in most suspensions, very few being electro-positive (e.g., barium carbonate). Suspensions of some fine powders, as lamp-black or kaolin, are precipi- tated by electrolytes in a similar manner as suspensoids. Acids can diminish the negative charge, completely neu- tralize it, or even import a positive charge; this effect is undoubtedly due to adsorption (see below) of the positive H ions. COLLOIDS 95 Adsorption. Colloidal particles attract ions having opposite electrical charges, and hold them, but not by entering into chemical combination. This phys- ical union is described as surface condensation; and the process is called adsorption. Other substances besides ions are adsorbed. Emulsoids adsorb to suspensoid particles, particu- larly if the colloids have opposite electrical charges. For example if Fe(OH) 3 (electro-positive suspensoid) is mixed with a faintly alkaline solution of protein (electro-negative emulsoid), on adding a salt both iron and protein are completely precipitated. EXPERIMENT. To 10 c.c. of blood serum add 70 c.c. of water, then 15 c.c. of colloidal ferric hydroxide solution and add powdered sodium sulphate, shak- ing after each addition, until a gelatinous precipitate forms. Filter, and test the filtrate for protein (biuret test, p. 282) with NaOH solution and a drop of dilute CuSO-t. Enzymes are supposed to be emulsoids. The substrate (the substance that is to be acted on) con- denses on the surface of the enzyme particle, and the rate of enzyme action at any particular moment is proportionate to the degree of adsorption. Other substances adsorb to enzymes, so that it is prac- tically impossible to separate enzymes in pure condition. The humus of the soil is an emulsoid colloid; it plays an important part in holding soluble salts in the soil by adsorption. Dyes adsorb to the fibers of cloth (see p. 407). 96 ORGANIC CHEMISTRY Crystalloids, enzymes, and colloids adsorb to insoluble particles suspended in a liquid. The high surface tension at the liquid-solid interfaces about the particles probably accounts for the inten- sity of the adsorption process. Finely powdered animal charcoal is one of the most effective agents for removal of substances from solution by adsorp- tion. It is used extensively for decolorizing liquids. The rate of adsorption is increased by shaking, also by heating; but the total amount adsorbed is less in a hot than in a cold liquid. Adsorption is re- versible, since the adsorbed substance may be removed, at least in part. For instance, lactose that has adsorbed to charcoal may be recovered by treating the charcoal with acetic acid, the more easily adsorbable acetic acid dislodging the lactose and being adsorbed in its stead. In some cases not all of the substance is adsorbed, the mixture coming to an equilibrium when a cer- tain proportion has been adsorbed. Some solu- tions should not be filtered, because the dissolved substance adsorbs to the paper too readily. In some cases chemical reaction follows adsorp- tion. This is undoubtedly what takes place in the manufacture of leather; tannin being first adsorbed to the tissue substance of the hide, and later forming insoluble compounds. Protective Colloids. When an emulsoid is added to a suspensoid solution, it exerts a protective action, preventing or hindering the precipitation of the suspensoid by electrolytes. This effect is believed to be due to adsorption of the emulsoid on the sus- COLLOIDS 97 pensoid, so that the latter acquires the .character of an emulsoid. EXPERIMENT, (a) To 5 c.c. of N/20 silver nitrate solution add three drops nitric acid and 5 c.c. of N/20 sodium chloride; a curdy precipitate is ob- tained. (6) Into one test-tube put 5 c.c. N/20 silver nitrate, 3 drops nitric acid and about 1 c.c. gelatin. Into another put 5 c.c. NaCl and 1 c.c. gelatin. Empty both simultaneously and at the sanle rate into a beaker. An opalescent solution (milky) which resembles glycogen solution is obtained. Now dilute and note carefully absence of precipitate. Photographic plates are made by taking advan- tage of the protective action of gelatin, which pre- vents precipitation of the silver salt. The therapeutic agent, collargol is a colloidal silver preparation, in which albumin acts as the protective agent. There being no Ag ions it is not toxic; bacterial action, however, changes it to ordinary silver and the ions act antiseptically. Swelling of Colloids. Many plant and animal tissues, also other gels (as starch, agar, gelatin, and other proteins) have the power of taking up water, so that they swell. In certain optimum concentra- tions acids and alkalies increase greatly the amount of water imbibed, CHAPTER V FORMULAE EMPIRICAL AND STRUCTURAL. ISOMERISM A KNOWLEDGE of the percentage composition and of the molecular weight of a substance, as we have seen, enables us to assign to it a formula indicating the number of atoms of each element present in the molecule. This is called the empirical formula. But it often happens that several organic substances with very different properties may have the same empirical formula. For example, there are no fewer than eighty-two compounds having the empirical formula CgHioOa. Such bodies having the same empirical formula are called isomers. It is evident, therefore, that a more detailed formula is necessary a formula, namely, in which the relations of the various atoms to one another (i.e., the grouping of the atoms) are indicated. Such a formula is called the structural formula. It is ascertained by acting on the substance with reagents which decompose it into simple bodies that can be identified ; in other words, we must tear the molecule apart. After some knowledge has been gained as to what simpler groups of atoms the body is composed of, an attempt is made to build up the substance by causing the simpler groups to unite, i.e., by synthesizing the sub- FORMULA, EMPIRICAL AND STRUCTURAL 99 stance. If the synthesis is successful, the structure of the molecule is proved. We see then that the structural formula is not only a graphical expression of the actual number of the various atoms present in a molecule of the sub- stance, but it is also an epitome of the more impor- tant reactions of the substance. In the chapters that immediately follow this one, the methods by which the various facts indicating the structure of the molecule are discovered will be fully explained (see especially acetic acid, p. 164). When we come to study the more complex sub- stances, we shall find that even the structural for- mula does not always suffice to differentiate the sub- stance, since, indeed, there may be several bodies having the same structural formula. In such cases it is supposed that the cause of the difference lies in the order of arrangement of the atoms in space. This subject will be found described in connection with lactic and tartaric acids (pp. 214 and 222). Before starting with a systematic study of the compounds of carbon, the student should bear in mind the extreme importance of the structural formula; he should never allow one to pass him without thoroughly understanding why it is so written. If he conscientiously follows this advice, he will soon find that organic chemistry is by no means the uninteresting and disconnected subject so many students think it to be. 100 ORGANIC CHEMISTRY SYNOPSIS OF CHAPTERS I-V. Determination of the Chemical Character of an Organic Compound 1. PURIFICATION. a. Methods. b. Tests of purity. 2. IDENTIFICATION. a. Physical properties. 6. Elementary analysis. 3. EMPIRICAL FORMULA. a. Elementary analysis. b. Molecular weight determination. 4. STRUCTURAL FORMULA. a. Reactions to detect the relative placing of atoms and groups of atoms in the molecule. b, Synthesis of the molecule, Physical Chemistry Topics 1. Osmotic pressure. 2. Electrolytic dissociation. 3. Hydrolytic dissociation. 4. Surface tension. 5. Viscosity. 6. Colloids (including adsorption), CHAPTER VI PRELIMINARY SURVEY OF ORGANIC CHEMISTRY BEFORE attempting to study the various organic substances individually, it is essential that we possess a general idea of their relationships to one another. Their number is so great that, did we attempt to remember the properties and reactions of each organic substance separately, we should utterly fail, and should, moreover, probably over- look one of their most important characteristics in contrast with inorganic substances, viz., their transmut ability into other organic compounds. In inorganic chemistry it is impossible to convert the compounds of one element into those of another element, except by substituting the elements. Each element has its own fixed chemical properties and compounds. In organic chemistry, on the other hand, as remarked above, we may consider all our substances as compounds of the element carbon and as being, therefore, convertible into one another. As is natural, we select as our basis of classifica- tion the very simplest organic substances, namely, those which contain carbon along with one other element. From our studies in inorganic chemistry we know that there are several elements with which carbon may be thus combined, e.g., with oxygen in C02, with sulphur in C$2, etc. We do not, how- ever, consider these as organic compounds, the 101 102 ORGANIC CHEMISTRY simplest organic compounds being those in which carbon is combined with hydrogen or with nitrogen. In union with nitrogen, carbon forms cyanogen (which is the lowest member of a group of com- pounds including hydrocyanic acid, HCN, cyanic acid, HCNO, sulphocyanic acid, HCNS) and the substituted ammonias. - In union with hydrogen, carbon forms the so- called hydrocarbons (i.e., hydro[gen] carbons). Prac- tically all the remaining carbon compounds may be considered as derived from these. The quantitative relationship between C and H in hydrocarbons is variable, so that we are enabled to subdivide hydrocarbons into several groups. If we express the hydrogen in terms of its proportion to carbon, we shall find that all the hydrocarbons group themselves into several series, four of which are of importance. The general formulae for the four series or groups are as follows: (1) C n H 2n+2 (3) C n H 2ra -2 (2) C n H 2ra (4) C n H 2n _ 6 (in the case of the fourth series n is at least 6.) - It will, moreover, be found that it is to the first and fourth of these groups that the great majority of hydrocarbons belong. If, now, we investigate the behavior of the mem- bers of these four groups towards hydrobromic acid, we shall find that members of the first and fourth groups do not readily react, whereas those of the second and third do; and indeed, that these directly combine with the reagent by addition, i.e., . PRELIMINARY SURVEY 103 without chemical substitution. We may, therefore, further subdivide our four groups into two, viz., saturated (1st and 4th) and unsaturated l (2d and 3d.) Of the two saturated groups it will be found that many members of the 4th group have an aromatic odor, whereas those of the 1st do not. The mem- bers of the 4th group are hence often styled aromatic compounds, and on account of the fact that the members of the 1st group are very resistant toward chemical reagents, they are called paraffins (parum affinis) . On account of their properties, then, we may amplify our classification into paraffins (1st group), unsaturated compounds (2d and 3d), and aromatic bodies (4th). 2 Compounds of the first three groups make up the ALIPHATIC OR FATTY DIVISION of organic chemistry. The compounds and derivatives formed by the various hydrocarbons of each of these groups are, in general, analogous, although the reactions by which they are produced may differ somewhat. If we understand the chemistry of the most important derivatives of one hydrocarbon in each group, we shall be able to infer approximately what the derivatives and reactions of all the other members of the group will be; and further, when we come to study the hydrocarbons of the other groups, we shall find many of their compounds quite similar to those already met with. 1 Only unsaturated compounds can form addition products. 2 The groups are also sometimes named from the lowest member of each, e.g., methane group, benzene group, etc. 104 ORGANIC CHEMISTRY From these preliminary remarks it will be evident that we must first of all take one group, and, having shown the relationship of its various members to one another, then study carefully the derivatives of some one or two of these members. Let us take the paraffins. They have the general formula C n H2 n +2. The following is a list of the most important members: Methane, CH 4 Butane, C 4 Hio Ethane, C2He Pentane, CsHi2 Propane, CsHs Hexane, CeHu It will be noticed that each differs from the one preceding it by CH 2 . They all form the same kind of derivatives, differing from one another again by CBb; thus the hydroxide or alcohol of methane has the formula CH 3 OH, and of ethane C2H 5 OH. Such a series is called an homologous series (cf. nitrogen oxides series). Let us consider why it should be that the increase of complexity is by CH 2 . To understand this we must remember that C is considered to have a valence of four; that, in other words, an atom of it can combine with four atoms of a monovalent element such as H, and that each of these valence bonds has exactly the same combining value. We may therefore write the structural formula for methane as follows: H H C H. PRELIMINARY SURVEY 105 When two methane molecules fuse together a hydrogen atom of each disappears and the liberated valence bonds unite as represented in the formula H H 1 I H C C H. Since each of the four valence bonds of C has the same value, it will be obvious that only one propane can exist: that we can write only one structural H H H formula for it, viz., H C G C H. But we may H H H have two varieties of the next member of the series, viz., butane, for, in adding an extra CH 3 group to propane, we may add it either to the central C atom of the chain or to one of the end ones, H I HH C HH H H H H H C- C C H, or H C C C C H III I I I I H H H H H H H and the properties of the corresponding body will vary accordingly; in other words, it makes a differ- ence when the extra CH 3 group is tacked on to a C atom in union with two H atoms (as is the case 106 ORGANIC CHEMISTRY with the central atom), and when on to one with three H atoms (as in the case of an end atom). When the substitution occurs in the center of the chain the resulting body is called an ^so-compound; when at the end it is normal. Such an iso-compound therefore contains a branched chain. Now, this isomerism applies not only to the methyl deriva- tives of propane for butane may be considered as such but also to all its derivatives, e.g., chlorides, hydroxides, etc. By using models instead of formulae these points Normal butane Isobutane can be still more clearly demonstrated: thus we may consider C as occupying the core of a tetra- hedron (made of wood), the four solid angles of which represent monovalent combining affinities, these angles being covered in the model by pyra- midal tin caps representing H atoms (see Fig. 22, p. 223). By removing an H cap from two models of methane and joining the two tetrahedra by the PRELIMINARY SURVEY 107 bared angles, we obtain the model of ethane. And, if by removing another H cap from ethane we unite three such tetrahedra, we obtain the model of propane. It does not matter which of the H caps we remove in these manipulations; the result- ing ethane or propane models are always the same. When we proceed to add another tetrahedron to propane, however, it will be evident that this can be done in either of two ways, by attaching it either to one of the end tetrahedra or to the central one; in the former case Uie model will represent normal butane, and in the latter isobutane; and so with the other homologues. We may also describe this progression from one hydrocarbon to the next higher as being due to the replacement of the H atoms of the former by the group CH 3 , called methyl. Now we may proceed with the derivatives of the paraffins. These are produced by the replacement of one or more of the H atoms of the simple hydro- carbons by various elements or groups of elements. Since, as explained, these derivatives are, in general, the same for each member of a series, we may choose any one of these and confine our attention for the present to its derivatives, remembering always that the corresponding derivative of any other member of the series will differ from it by just as many CH 2 groups as did the original hydrocarbons differ from one another. In inorganic chemistry t.v^. halogen compounds, * the oxides, and the hydroxides are among the most important compounds of an element, and the same 108 ORGANIC CHEMISTRY applies to the hydrocarbons: each has halogen derivatives, oxides (ethers), and hydroxides (al- cohols). Beyond these, however, the analogy breaks down, for whereas an inorganic hydroxide is an ultimate product and cannot be further oxidized, an organic hydroxide (or alcohol) can be oxidized so as to yield various substances according to the extent of the oxidation and the nature of the alco- hol started with. We may, therefore, classify our derivatives thus: Halides. Oxides or ethers. Hydroxides or alcohols. Oxidation products of alcohols. Halides. When the paraffins are brought into contact with chlorine, substitution of one or more of the H atoms occurs. Thus, taking methane, we may have monochlormethane, dichlormethane, trichlormethane (chloroform), and tetrachlorme- thane. In connection with the monohalogen sub- stitution products it should be pointed out that they may be considered as derived from a halogen acid, the H of the acid having been replaced by a hydrocarbon minus one of its H atoms. The general term for all such groups is alky I, and the specific names for the alkyls are methyl (CH 3 -), ethyl (C2H 5 -), propyl (CsHj-), and so on. An alkyl is, therefore, analogous with a monovalent element or with NH 4 -. Halogen atoms may likewise displace one or more of the H atoms of the alkyl radicle when this latter PRELIMINARY SURVEY 109 is already in combination with some other substitut- ing group. Thus, chloral is trichloraldehyde, CC1 3 CHO, aldehyde being CH 3 CHO. Oxides (or ethers). Since oxygen combines with two atoms of a monovalent element, fas in sodium oxide, Na2O, the lowest alkyl oxide will have the formula yO. To this group belong the ethers, 25\ common ether being XX / Hydroxides (or alcohols) . When one of the H atoms of methane is replaced by hydroxyl, OH, methyl H I alcohol is formed. Thus H C H becomes H H H C OH, and it does not matter which of the H H atoms is thus replaced, the resulting compound being always the same. The same is true for ethane and its alcohol, ethyl alcohol, CH 3 CH 2 OH. When we come to form the alcohol from propane, however, we encounter conditions analogous with those which exist when butane is formed from propane (see p. 106); we may add the OH group to a C atom of propane that is in combination with three hydrogen atoms or to one in union with two such, and the resulting product, as we have seen, 110 ORGANIC CHEMISTRY will exhibit different properties. Consequently we have two forms of propyl alcohol. Of these the OH group in the one is attached at the end of the chain, CH 3 CH 2 CH 2 OH; in the other it is attached OH in the middle of the chain, The CH 3 CH CH 3 . former is called a primary alcohol, the latter a secondary alcohol. In the case of butane, we may have the hydroxyl radicle at the end of the chain, CH 3 CH 2 CH 2 CH 2 OH (primary butyl alcohol); or attached to a C atom in the center of the chain with one other H /OH atom attached to it, CH 3 CH 2 CH CH 3 CH - CH 3 (Normal butane) CH 3 (Isobutane) Isopentanes. There are several pentanes: CH 3 CH2 CH2 CH2 CH 3 \ CH 3 CH CH.2 CH 3 j (Normal pentane) CH 3 (Isopentane) CH 3 CH 3 C CH 3 CH 3 (Neopentane) The newer nomenclature designates these isomers as derivatives of methane; thus, isopentane is dimethylethyl-methane, and neopentane is tetra- methy 1-met hane . In the case of hexane still another kind of iso- hydrocarbon is possible, in which there are two branches attached to different (inside) C atoms of the chain. CHAPTER VIII HALOGEN SUBSTITUTION PRODUCTS OF THE PARAFFINS IF only one hydrogen atom of the hydrocarbon is replaced by a halogen atom, the compound is called an alkyl halide (or alkyl halogenide), because it con- sists of a halogen atom linked to an alkyl radicle, e.g., CH 3 Cl (see p. 108). The alkyl halides derived from methane are: methyl chloride or monochlormethane, CH 3 C1; methyl bromide or monobrommethane, CH 3 Br; methyl iodide or monoiodomethane, CH 3 I. General Methods of Preparation. (1) The chloride and bromide can be produced from methane by mixing chlorine or bromine with it and exposing the mixture to diffused sunlight. (2) All may be secured by acting on methyl alcohol with the proper halogen acid, in accordance with the following equations: CH 3 |OH+|[|C1 =CH 3 C1+H 2 O, CH 3 |OH+H|Br = CH 3 Br +H 2 O, CH 3 :OH+Hll =CH 3 I +H 2 O. (3) Another method of obtaining them is by the action on methyl alcohol of PC1 3 , PBr 3 , and Pis: 124 HALOGEN SUBSTITUTION PRODUCTS 125 3CH 3 OH+PC1 3 = 3CH 3 C1+P(OH) 3 , 3CH 3 OH+PBr 3 = 3CH 3 Br+P(OH) 3 , 3CH 3 OH+PI 3 = 3CH 3 I +P(OH) 3 . In a manner exactly similar to the last two methods the ethyl halides can be derived from ethyl alcohol. Some of the More Important Alkyl Halides. Methyl chloride (monochlormethane), CH 3 C1, is a gas under ordinary conditions. It is readily lique- fied, the liquid boiling at -23.7. Ethyl chloride (monochlorethane), C2H 5 C1, is a liquid boiling at 12.2. It is put up in glass or metal tubes, and is used for local anaesthesia by spraying the liquid on the skin. The rapid evapora- tion causes the abstraction of enough heat from the skin to result in freezing the latter. Its vapor is very inflammable. It can be used also as a general anaesthetic, 1 being administered as a vapor by inhalation. Ethyl bromide (monobromethane), C2H 5 Br, is a liquid resembling chloroform in odor, density, and physiological effect. It boils at 38.37 (at 37.1- 37.4 under 737 mm. pressure), and its specific gravity is 1.468 at 13. It may be obtained by any of the general methods, but is best prepared by the action of ethyl sulphuric acid on - potassium bromide, as in the following experiment. 1 In this book brief pharmacological statements are fre- quent. For full information on these points consult the excellent pharmacology text-books by Cushny and by Sollmann. 126 ORGANIC CHEMISTRY EXPERIMENT. Into a 250, c.c flask put 55 c.c. of concentrated sulphuric acid; add quickly 55 c.c. of ethyl alcohol, shaking at the same time. Cool the flask by holding it in running water, add 38 c.c. of iced water, and cool again. Meanwhile set up a condenser having an adapter attached. Use a rapid stream of water in the condenser. Put into the flask 50 gm. of powdered potassium bromide, FIG. 19. then place the flask on a sand-bath and attach to the condenser. Fill an Erlenmeyer flask one-third full of ice-water and have the adapter dip below the surface of the water. Place this receiving flask in a bath of cold water. Heat rapidly and continue heating as -long as any distillate comes over. Watch that the contents of the receiver be not sucked up into the condenser. If this is threatened turn the adapter so that air can enter it. Decant most of the water from the ethyl bromide, HALOGEN SUBSTITUTION PRODUCTS 127 then add ice-water and agitate. Decant the water. Wash several times in this manner. Finally shake the washed ethyl bromide with a dilute sodium carbonate solution; do not, however, cork the flask. Transfer the bromide to a separating funnel, and run out the bottom layer into a dry flask. Add dry calcium chloride, cork tightly, and let it stand in a cool place. After a day or so distill from a small fractionating flask, using a water-bath. Place an empty receiving flask in cold water. Note the boiling-point. Take the specific gravity in a small picnometer holding 5 or 10 c.c. The following equations will explain the reactions: C 2 H 5 OH +H 2 SO 4 = CH 3 CH 2 HSO 4 +H 2 O, (Ethyl alcohol) (Ethyl sulphuric acid) CH 3 CH 2 , HS0 4 +KBr = CH 3 CH 2 Br +KHSO 4 . (Ethyl bromide) (Acid potassium ilphate) sui Other halogen derivatives (besides the alkyl halides) are illustrated by the following compounds : dichlor- methane, CH 2 C1 2 ; dibrommethane, CH 2 Br 2 ; diiodo- methane, CH 2 I 2 ; trichlormethane, CHC1 3 ; tri- brommethane, CHBr 3 ; triiodometnane, CHI 3 ; and tetrachlormethane, CC1 4 . Of the many compounds thus derived from the paraffins the three trihalogen substitution products of methane are the only ones of importance. Chloroform (trichlormethane), CHC1 3 , is a liquid having a pleasant odor and a sweetish taste. Its boiling-point is 61 at 73 1 mm. Its specific gravity is 1.498 at 15, 1.5039 at ii~-. It is slightly soluble in 128 ORGANIC CHEMISTRY water, one liter of water dissolving 8 gm. of chloro- form, while, on the other hand, one liter of chloro- form can take up 3 gm. of water. It is a good solvent for many substances. Chloroform is a very use- ful general anaesthetic, but is considered much less safe than ether. Since it is not inflammable, it can be used at night as an anaesthetic where only lamp or gas-light is available. Chloroform vapor should not be allowed to come in contact with a flame, as noxious gases are produced. It is not a stable compound, as exposure to light, air, and mois- ture causes some decomposition, thus furnishing the poisonous impurities, chlorine, hydrochloric acid, and carbon oxy chloride or phosgene (COCU). These impurities can be readily detected, since chloroform containing them gives a precipitate when shaken with silver nitrate solution. Pure chloroform or other halogen substitution products do not immediately give a precipitate with silver nitrate, because they furnish no halogen ions (see p. 69). The addition of alcohol to chloroform, to the extent of 0.6%, prevents decomposition. The method of its preparation is given in the follow- ing experiment. Chlorine (from bleaching-powder), acts to chlorinate acetone, and from the product by the action of the calcium hydroxide present in the mixture, chloroform is produced. Alcohol may be used instead of acetone. EXPERIMENTS. (1) Preparation. Into a liter flask put 150 gm. of bleaching powder (calcium hypochlorite) and 450 c.c. of water, and mix them HALOGEN SUBSTITUTION PRODUCTS 129 thoroughly. Add slowly a mixture of 16 c.c. of acetone and 35 c.c. of water. Connect the flask with a steam generating flask and with a condenser, as for steam distillation (p. 16). Pass steam as long as droplets of chloroform appear with the water at the end of the condenser. Transfer the distillate to a separating funnel, draw off the chloro- form and wash it with several small portions of water. Run the chloroform into a dry flask, add calcium chloride, cork, and let it stand a day or so. As the yield is small, it need not be redistilled, but can be sealed up in sample bottles. The following equations will explain the reaction : CH 3 CO CH 3 +6CI = CC1 3 CO - CH 3 +3HC1, 2CC1 3 CO CH 3 +Ca(OH) 2 = 2CHC1 3 + (CH 3 -COO) 2 Ca. (2) To 1 c.c. of chloroform add half a test-tube of distilled water and shake vigorously. Remove the water with a pipette. Wash three times in this manner, testing the last wash-water with silver nitrate solution; if no precipitate appears, add silver nitrate to the washed chloroform. Let it stand, observing whether a precipitate forms later. Bromoform (tribrommethane), CHBr 3 , is a liquid which boils at 146 at 751 mm. On cooling it becomes solid, melting at 8. Its specific gravity is 2.885 at 15. It has been used as a medicine. lodoform (triiodomethane), CHI 3 , is a yellow crystalline solid, the crystals having the form of hexagonal plates. Its odor is peculiar and charac- 130 ORGANIC CHEMISTRY teristic. It melts at 119. Its specific gravity is 4.008. It is used in surgery as an antiseptic, the action being probably due to iodine which is freed. It is manufactured from acetone by the action of iodine and potassium carbonate. Its method of preparation is illustrated in the following experi- ment: EXPERIMENTS. (1) Dissolve 5 gm. of sodium carbonate in 30 c.c. of warm water, add 5 c.c. of alcohol, heat in a water-bath to 70-80, and add a little at a time 3 gm. of powdered iodine, shaking frequently. If the liquid has become brown, add just enough sodium carbonate solution to change it to a pale yellow. After cooling, filter and wash the crystals. After being dried in a desiccator, a melt- ing-point determination may be made. The reactions involved are doubtless the produc- tion of iodal, CIs-CHO, by the action of NalO; then the conversion of iodal by the action of the alkali present into iodoform and sodium formate. (2) Make a yellow solution of iodoform in alcohol, and set it aside loosely covered; by slow evaporation of the alcohol hexagonal crystals of considerable size are formed. This reaction, besides being given by alcohol, is given by aldehyde, acetone, and other compounds that contain the group CH 3 CO , provided the CO is not part of a carboxyl group. On account of its characteristic strong odor, the production of iodoform in this manner is often used as a test for HALOGEN SUBSTITUTION PRODUCTS 131 the presence of alcohol or other substances containing the above group. lodoform Substitutes. Because of the unpleasant odor of iodoform many antiseptic preparations have been put on the market which disguise or eliminate the bad odor. Such are eka-iodoform (iodoform with paraformaldehyde), iodoformin (iodoform with hexa- methylenetetramine), iodoformogen (protein com- pound of iodoform), and anozol (iodoform and thymol). lodol (see p. 414) and possibly aristol (see p. 344) liberate iodine in the tissues, so that they are suitable substitutes for iodoform. Diiodoform is tetraiodoethylene, C2l4 (see ethylene, p. 299). Tetraiodomethane, Cl4, is a solid, having a very high specific gravity, 4.32. Similar to the alkyl halides are the alkyl combinations with metals, as zinc methyl, Zn(CH 3 ) 2 , and sodium methyl, NaCH 3 . Both of these are important reagents. CHAPTER IX ETHERS THE alkyl oxides are called ethers. They con- sist of two organic radicles linked to an oxygen atom, as methyl ether, CH 3 O CH 3 ; ethyl ether, C2Hs O C2H5. A general method of synthesis is shown by the following equations ; CH 3 -0 |Na+I| CH 3 = CH 3 O CH 3 +NaI, (Sodium methylate) (Methyl iodide) (Methyl ether) C 2 H 5 - OjNa +IiC 2 H 5 = C 2 H 5 O C 2 H 5 +NaI. (Sodium ethylate) (Ethyl iodide) (Ethyl ether) Methyl ether is a gas and is unimportant. Ethyl ether is common ether. Pure ether is a liquid, boiling at 35 (33.6 at 734 mm. barometric pressure) and having a specific gravity of 0.718 at 25 15.6 and 0.7079 at ?L. It dissolves to a certain extent (about 6.5%) in water; it also takes up about If % of water. If ether is allowed to stand for some time over magnesium bromide both water and alcohol will be abstracted from it by the salt. To obtain absolute ether, it is necessary to treat 132 ETHERS 133 the ether with metallic sodium and then distill (Na +H 2 = NaOH +H) . It vaporizes readily, and, when rapidly evaporated, abstracts enough heat to freeze water if the latter is contained in a small vessel surrounded by the ether. The vapor is heavier than air and consequently falls. It is very inflammable, and should therefore be kept away from a flarne. Ether is a solvent for a great number of substances. It is extensively used as an anaesthetic, being reasonably safe when properly administered. Heat is liberated when chloroform and ether are mixed in certain proportions. Because of the use of sulphuric acid in its produc- tion, it is sometimes called sulphuric ether. To pre- pare it, ethyl alcohol is allowed to flow slowly into heated ethylsulphuric acid (see p. 127) contained in a flask. The following experiment will make clear how this is done: EXPERIMENT. In a liter Jena flask mix 165 c.c. of C.P. H 2 SO 4 with 210 c.c. of alcohol. Fit a cork, pierced with three holes, into the mouth of the flask, One hole is to admit the bent tube connecting with the condenser, another holds a thermometer, and the third is for a dropping funnel which contains ethyl alcohol. The bulb of the thermometer is immersed in the liquid. A better arrangement is to introduce alcohol into the ethylsulphuric acid in the form of vapor. For this it is necessary to have an extra flask in which to boil alcohol, which is connected with a tube extending to the bottom of the ether generator flask. When all is ready, 134 ORGANIC CHEMISTRY place the flask on a sand-bath and connect with the condenser. Submerge the receiving flask in a cold bath and use .an adapter (cf. ethyl bromide, p. 126). Heat rapidly until the ethylsulphuric acid has a temperature of 140, at which point it must be kept for the rest of the process. Run in a very little alcohol from the funnel, or vapor from the alcohol flask. At intervals, i.e., when the amount of ether vapor diminishes, add more alcohol, a few cubic centimeters at a time. Keep flames away from the vicinity of the receiving flask. Watch the apparatus constantly. When sufficient distillate has been secured, wash it with dilute NaOH solu- tion in a separating funnel, then with several small portions of water; draw off the water, pour the ether into a dry flask, add calcium chloride, and cork tightly. Redistill after a day or so, using a water-bath. The following equations will explain the reaction: C 2 H 5 OH +H 2 S0 4 = C 2 H 5 HS0 4 +H 2 O, (Ethyl alcohol) (Ethylsulphuric acid) C 2 H 5 H + HS0 4 : C 2 H 5 = C 2 H 5 C 2 H 5 +H 2 S0 4 . (Ether) Mixed ethers contain two different organic radicles linked to the same oxygen atom, as methyl ethyl ether, CH 3 O C 2 H 5 . They may be formed by a synthetic process similar to that described above for simple ethers, thus: CH 3 O!Na+I:C 2 H 6 = CH 3 C 2 H 5 +NaI. ETHERS 135 It is interesting to note that the boiling-point of methyl ethyl ether (11) is intermediate between that of dimethyl ether, (CH 3 ) 2 O (-23.6), and that of diethyl ether, (C 2 H 5 ) 2 (34.6). The ethers are very stable, not being affected by boiling with alkali or dilute acid. CHAPTER X PRIMARY ALCOHOLS AMONG the most important classes of organic com- pounds are the alcohols. The empirical formula of a monacid alcohol can be derived from the formula of the paraffin hydrocarbon containing the same num- ber of carbon atoms, by attaching an atom of oxygen, thus: C n H 2n+2 O. Alcohols, however, are not oxides of the hydro- carbons. They are hydroxides. A primary alcohol is an alkyl hydroxide. Alcohols cannot be obtained by direct oxidation of the hydrocarbons. That the oxygen atom is present in hydroxyl is proved by the following reactions : (1) CH 3 |OH +H|CI = CH 3 C1 +HOH (Methyl alcohol) (Methyl chloride) (cf. K|OH+H|CI =KCI+HOH), (2) 3CH 3 OH+PC1 3 = 3CH 3 C1+P(OH) 3 (Phosphorus (Phosphorous trichloride) acid) (cf. 3HOH+PC1 3 =3HC1+P(OH) 3 ), (3) CH 3 OH +H 2 S0 4 = CH 3 HS0 4 +HOH (cf. KOH +H 2 S0 4 =KHS0 4 +HOH). (4)CH 3 OH+CH 3 -COOH=CH 3 -COO-CH 3 +HOH (Acetic acid) (Methyl acetate) (cf. KOH+CH 3 -COOH = CH 3 -COOK+HOH). 136 PRIMARY ALCOHOLS 137 The striking similarity between the reactions of alcohol and the most typical of all hydroxides (viz., KOH and H^O) is clearly shown by these reactions. The reaction of potassium and sodium 1 with alcohols shows further that one particular hydrogen atom of the latter has a different linking from that of the other three hydrogen atoms : CH 3 OH +Na = CH 3 ONa +H (Sodium methylate) (cf . HOH +Na = NaOH +H) . Finally, the structure of an alcohol is settled be- yond a doubt by its synthesis from an alkyl halide by the action of a strong hydroxide : CH 3 ]cT+K|OH = CH 3 OH +KC1. Inorganic hydroxides are strong bases, because they furnish many hydroxyl ions when dissolved in water (see p. 172). Alcohols, on the other hand, are not bases; they ionize very slightly, if at all. It is to be noted that the change of one hydrogen atom of the hydrocarbon molecule into hydroxyl greatly alters the chemical behavior of the com- pound; the paraffin is very stable and enters into reaction with few reagents, whereas the alcohol is reactive, being readily affected by many reagents. The heat of combustion of an alcohol is less than that of the corresponding hydrocarbon. This is just what we should expect since there is oxygen in the alcohol molecule. 1 The higher alcohols are hardly affected, the fewer the C atoms in the alcohol the more vigorous is the sodium action. 138 ORGANIC CHEMISTRY MONACID PRIMARY ALCOHOLS. These comprise the most important group of alcohols. They form an homologous series begin- ning with methyl alcohol. There is a regular in- crease of specific gravity and boiling-point from the lowest to the highest members of the series. Methyl alcohol (methanol, carbinol), H-CH 2 OH or CHsOH, is obtained from the distillate produced by the destructive distillation of wood (see p. 162). The crude alcohol is therefore called wood alcohol. It is also secured by destructive distillation of vinasse, which is the residue left after ordinary alcohol has been distilled off from fermented beet sugar molasses. Fractional distillation does not suffice to free the methyl alcohol from the acetic acid, acetone, and other constituents of crude wood spirits. A crys- talline compound, methyl oxalate (CHs)2C2O4, can be formed by treatment with oxalic acid. The purified crystals can then be decomposed by boiling with ammonia water, yielding pure methyl alcohol. If the crude alcohol be treated with calcium chloride, CaCU^CHsOH is formed; this is not affected by heating to 100, but acetone is driven off. Treatment with water sets the alcohol free, and distillation completes the purification. Methyl alcohol boils at 66 and its specific gravity 1 ^ A 90 at *2- is 0.7931 (at ^ it is 0.7913). Its melt- 15. o 4 ing-point is higher than that of ethyl alcohol, 93.9. Electrolytes dissolved in methyl alcohol PRIMARY ALCOHOLS 139 ionize readily. It mixes readily with water, exhibit- ing the phenomena of contraction of volume and liberation of heat. It is a useful solvent; in con- sequence, the crude alcohol is used in the prepara- tion of paints. It is intoxicating if taken inter- nally; wood alcohol is dangerous, having caused many deaths when used as a substitute for ethyl alcohol. Wood alcohol burns with a blue flame, hence its use in alcohol lamps. Ethyl alcohol (ethanol), CH 3 -CH 2 OH or C 2 H 5 OH, is common alcohol. Its relation to methyl alcohol is seen when it is considered as methyl alcohol in which one hydrogen atom is replaced by the methyl radicle : H CH 2 OH -> CH 3 CH 2 OH. The name methyl carbinol expresses this relation. Similarly the higher alcohols are called carbinols (the prefix in each case indicating the groups attached). Alcohol is produced by fermentation of .dextrose (glucose) by means of yeast. C 6 Hi 2 6 = 2C0 2 +2CH 3 CH 2 OH. (Dextrose) About 5% of the dextrose forms by-products, such as amyl alcohol, glycerol (i.e., glycerine), and succinic acid. It has been thought that lactic acid is an intermediate product of yeast fermen- tation; and that it is converted into acetaldehyde and formic acid, the latter in turn giving up H (and evolving C0 2 ), which adds itself to the aldehyde 140 ORGANIC CHEMISTRY molecule, and thus ethyl alcohol results. This theory has not been proved, and is rather discoun- tenanced by the fact that yeast will not produce alcohol from lactic acid, nor from an equimolecular mixture of formic acid and acetaldehyde (even when these are gradually set free in the reaction mixture). Another theory advances pyruvic acid as the first in- termediate product of yeast action. No theory has as yet sufficient experimental evidence in its favor. Alcoholic beverages are obtained by fermentation of fruit juices containing sugar, as wine from grapes, or of malted grain, as beer from barley. Fermenta- tion is inhibited when the alcohol content reaches about 17% (by volume). Malt liquors contain from 2 to 8% of alcohol. Wines contain 8 to 15%. Stronger wines are made from these by adding alcohol. Brandy is obtained by distillation of wine, whiskey by distillation of fermented grain; both of these contain 40 to 60% of alcohol Many liquors require aging in order that the by-products, which are disagreeable and injurious, as for instance fusel- oil, may be converted into ethereal compounds of pleasant taste and odor. The amount of alcohol present in a liquor can be readily estimated by distilling 100 c.c. of the liquor (diluted with 50 c.c. of water); when 100 c.c. of distillate has been collected, its specific gravity is determined. The percentage of alcohol is found by referring to tables of specific gravities (see Appendix, p. 445). Preparation. Commercial alcohol is made from the cheapest forms of starch, potato or corn. The ground or mashed raw material is heated until the PRIMARY ALCOHOLS 141 starch is thoroughly cooked. After cooling malt 1 is added and the mixture is kept at 60-62. Malt contains a ferment, diastase, which changes starch into the sugar maltose, and, to the extent of about 20%, into dextrin. The sugar solution is diluted, and yeast is added. The yeast furnishes a ferment that splits or in- verts the maltose molecule into two dextrose mole- cules, and also a ferment that decomposes the dex- trose into alcohol and carbon dioxide. These ferments can be extracted from the yeast cells by grinding the latter with fine quartz sand, subject- ing the mass to a very high pressure (up to 300 atmospheres), and finally filtering the extract through porcelain. This filtrate contains no yeast cells, but it inverts maJiosa^jnto dextrose and changes dextrose into alcohol. The ferment in this extract from yeast cells is called zymase. Similar intracellular ferments can be obtained from certain bacteria. Ferments are often called enzymes. The weak alcoholic solution (not over 13%) obtained by this process of fermentation is distilled in an apparatus containing a fractionating column. The crude distillate (90% alcohol) is filtered through animal charcoal, which removes many impurities. It is then redistilled, the product being ordinary alcohol (95%) . This is apt to contain some aldehyde. The strongest alcohol obtainable by the most careful fractionation contains 4.5% by weight 1 Malt is obtained by allowing barley to germinate to a certain stage. 142 ORGANIC CHEMISTRY of water. Commercial absolute alcohol contains about one-half of 1% of water. It is obtained by digesting alcohol with quick-lime and then distilling (CaO+H 2 O=Ca(OH) 2 ). More nearly absolute alcohol is secured by treating with metallic sodium and distilling. In Europe potatoes are used for alcohol production, but in this country corn starch is the material used, 2.7 gallons being secured from one bushel of corn. The cost of the process of manu- facture exclusive of the cost of the raw material is said to be very low, less than five cents per gallon. Properties. Chemically absolute alcohol is almost unknown, because it takes up moisture so rapidly when exposed to the air. Absolute alcohol has a 1 ^ ^f\ i ^ specific gravity of 0.79365 at ^_, 0.79357 at ^ lo.oo 4 and boils at 78.3 (corrected) (at 734 mm. pressure it boils at 77.7). It solidifies at -112. It has much less odor than common alcohol. Commercial absolute alcohol (dehydrated alcohol) contains 99% by weight, and has a specific gravity of 0.798 at 15. Alcohol containing 95.57% by weight has the lowest boiling-point of any alcohol preparation, 78.15 at 760 mm. Alcohol is of great service as a solvent. Alcohol burns with a colorless flame. When mixed with water, rise of temperature and contraction of volume are observed. It is an intoxicant; the detrimental effect of alcoholic liquors, however, is due in part to other compounds besides the alcohol. Methylated or denatured alcohol is alcohol to which wood alcohol or nauseous substances have been added to render it unfit to drink. In the United PRIMARY ALCOHOLS 143 States 10 parts of wood alcohol and 1 or 2 parts of benzine, or else 2 parts of wood alcohol and 1 or 2 parts of crude pyridine per 100 parts of alcohol, are used. Such alcohol can be sold duty-free in many countries. EXPERIMENT. Into a large bottle or flask put 500 c.c. of 10% glucose solution, and add some crumbled yeast. Through a cork that tightly fits the bottle or flask, pass a glass tube bent so as to extend down into a small bottle containing some baryta water, the tip of the tube jtist reaching the surface of the latter; through a second hole in its cork the baryta bottle is connected with a tube or tower of soda-lime. Thus C02 cannot enter the apparatus from without. Let it stand a few days, after which a copious precipitate of BaCOs is obtained. Experiments with 95% alcohol. (1) Shake 10 c.c. in a test-tube with anhydrous CuSO* and let it stand (corked) one hour; the CuSCX becomes bluish (with absolute alcohol no blue color appears). Explain what takes place. (2) Take 52 c.c. of alcohol and 48 c.c. of water, each being at a temperature of 20, mix them in a 100-c.c. graduate, and note the maximum tempera- ture, cool to 20, and read off the volume (about 96.3 c.c. instead of 100 c.c.). When miscible liquids are mixed a change in volume is generally noticed, usually a decrease (sometimes an increase). Heat may be either absorbed or given off. 144 ORGANIC CHEMISTRY (3) Put 10 c.c. of alcohol in a test-tube, and add as a bottom layer 5 c.c. of concentrated sulphuric acid. Throw in a number of small crystals of potas- sium permanganate. Flashes of fire will occur in the liquid in the zone of contact of the alcohol and acid (probably due to ozone production, and intense oxidation of a derivative of alcohol). Propyl alcohol is a primary alcohol having the formula, CH 3 - CH 2 - CH 2 OH. Normal butyl alcohol is CH 3 -CH 2 -CH 2 -CH 2 OH. Primary isobutyl alcohol is CH 3 -CH-CH 2 OH. I CH 3 As with hydrocarbons the branching of the chain lowers the boiling-point. Normal amyl alcohol is CH 3 CH 2 CH 2 CH 2 CH 2 OH. Primary isoamyl alcohol, called isobutyl carbinol, is CH 3 CH CH 2 CH 2 OH ; this is the main constituent CH 3 of fermentation amyl alcohol. Both of these amyl alcohols are contained in fusel-oil and in certain liquors, especially recently distilled brandy and whiskey. There are three isoamyl alcohols having the same structural formula, CHav/H CH 3 -CH 2 / \CH 2 OH. Their chemical and physical properties are identical, except that their action on polarized light is different. PRIMARY ALCOHOLS 145 One rotates the beam of light to the left, another rotates it to the right these are the active amyl alco- hols; the third does not cause rotation and is called inactive amyl alcohol. 1 There is also another amyl alcohol containing the primary alcohol group, CH 3 \ /CH 3 CH 3 / \CH 2 OH. There are four secondary amyl alcohols, two normal and two isoamyl alcohols. There is a tertiary isoamyl alcohol v / / \ OH CH 3 / \CH 2 CH 3 , which has been used as a hypnotic under the name amylene hydrate. Fusel oil contains normal propyl alcohol, primary isobutyl alcohol, primary isoamyl alcohol and the optically active (primary) isoamyl alcohol. Solubility of alcohols. The hydroxyl group tends to render a compound soluble in water; the fewer the carbon ,atoms the more soluble the alcohol. Methyl, ethyl and propyl alcohols mix with water readily, while 30 parts of butyl alcohol and only 6 parts of amyl alcohol dissolve in 100 parts of water. 1 For a discussion of this form of isomerism, see p. 214. CHAPTER XI ALDEHYDES IF a primary alcohol be oxidized, the first product is an aldehyde: CH 3 CH 2 OH +0 = CH 3 CHO +H 2 0. Two atoms of hydrogen have been removed from the alcohol molecule, hence the name al(cohol) dehyd(rogenatus) . The reaction is more accurately indicated as follows : CH 3 CH 2 OH +0 = CH 3 - CH bll Two hydroxyls become attached to the same car- bon atom, but, as is the rule 1 in organic compounds, such a combination is too unstable to persist and H 2 splits off. It is to be noticed that the aldehyde group CHO contains no hydroxyl. This can be proved experi- mentally. If alcohol or any other hydroxyl-contain- ing compound be treated with phosphorus penta- chloride, the place of each hydroxyl group is taken by one chlorine atom: CH 3 CH 2 OH +PC1 5 = CH 3 - CH 2 C1 +POC1 3 +HC1. 1 There are three well-known exceptions to this rule chloral hydrate, mesoxalic and glyoxylic acid. 146 ALDEHYDES 147 But if an aldehyde is similarly treated, a dichlor-com- pound is obtained: CH 3 CHO +PC1 5 = CH 3 CHC1 2 +POC1 3 . Therefore the aldehyde group must be written CHO, or CO H. Nascent hydrogen converts an aldehyde into the corresponding primary alcohol. The aldehydes are named from the acids they produce when oxidized: thus, H-CHO is formic aldehyde or formaldehyde, and CH 3 -CHO is acetic aldehyde or acetaldehyde. Aldehyde reactions. (1) All aldehydes are strong reducing agents, because they readily take up oxygen to form acids. The common tests for sugar are really aldehyde reactions, as practically all sugars contain the CHO group. The reduction of silver and copper salts is illustrated by the experi- ment below. (2) The linking C in the aldehyde group causes aldehydes to act like unsaturated compounds, for they readily form addition compounds, thus: ,0 /0-H CH 3 C< +HCN=CH 3 C^ - CN, X H \H (Acetaldehyde) (Acetaldehyde cyanhydrin) .0 /0-H CH 3 Cf +NH 3 =CH 3 C(- - NH 2 , X H \H (Aldehyde ammonia) .0 X H CH 3 Cf +NaHS0 3 =CH 3 Ce S0 3 Na. X H \H (Sodium acid sulphite) (Aldehyde bisulphite) 148 ORGANIC CHEMISTRY (3) Phenylhydrazine can combine with an alde- hyde by removing O of the carbonyl group, a hydrazone being formed. (4) Aldehydes (except chloral hydrate) cause a violet-red color to appear when added to a solution of fuchsin which has been decolorized by sulphurous acid. This reaction is due to the formation of con- densation products (see acetaldehyde). Dextrose does not give this test because, as in the case of chloral hydrate, it does not contain a C =O group; however, in the case of both of these compounds the aldehyde character appears under the influence of the strong reagents (and the heat) used for other tests. Formaldehyde (methanal), H-CHO, is a gas. It is very soluble in water. Commercial formalin is a 40% solution. Formaldehyde is prepared by bub- bling air through methyl alcohol, which is kept at about 50; then the mixture of air and vapor is passed through a heated tube containing platinized asbestos: H-CH 2 OH+0=H.CHO+H 2 O. . It is also produced by burning methyl alcohol in a special lamp in which the supply of air is limited, so that incomplete combustion occurs; part of the alcohol is oxidized to formaldehyde and escapes. This lamp can be used for disinfection of rooms, but is not very satisfactory. Formaldehyde has a tendency to form polymers. A polymer has a molecular weight which is an even multiple of that of the original substance, and it has the same percentage composition as the lat- ter. Thus paraformaldehyde (trioxymethylene) is (H CHO)s. Its graphic representation is ALDEHYDES 149 H I/H C/ o o (X H' | N H H H Paraformaldehyde (paraform) is a white sub- stance, which, on being heated, is converted into formaldehyde. It is sold in the form of tablets or candles for disinfecting purposes. With ammonia, formaldehyde does not form a simple addition compound as do other aldehydes, but a complex substance, hexamethylentetramine (see p. 264). Formaldehyde is an efficient germicide, and is therefore used extensively for disinfecting pur- poses. It is used either as the gas or in dilute solu- tion. It is very irritating to the eyes and mucous membranes. The dilute solution also hardens al- buminous substances, and is consequently used to prepare tissues for histological examination. It converts a solution of gelatin into a hard insoluble mass. Glutol is a substance produced by the action of formaldehyde on gelatin. In the form of a dry powder it is used as a surgical dressing for raw surfaces. It is said to act as an antiseptic because of slow liberation of formaldehyde. 150 ORGANIC CHEMISTRY EXPERIMENTS. (1) To a few cubic centimeters of concentrated H 2 S04 in a test-tube add a few drops of ferric chloride solution; with a pipette run in about 5 c.c. of milk containing 5 drops of 1 : 5000 for- maldehyde solution as a top layer, avoiding mixing with the H 2 S04. A violet zone forms between the two layers. (2) Set in a desiccator an evaporating dish containing 5 c.c. of formalin. Leave several days until a white solid, paraformaldehyde, is obtained. When this is secured, heat some of it in a dry test- tube. It volatilizes completely, passing away as formaldehyde gas. Note the odor. Be careful not to get strong fumes into the eyes or nostrils, as the gas is very irritating. (3) To 10 c.c. of milk in a large evaporating dish add a little formaldehyde and 10 c.c. of concentrated hydrochloric acid containing one drop of 5% ferric chloride. Heat over the flame, holding the dish in the hand and maintaining a rotary motion." At about 90 the mixture acquires a violet color. (4) Add 4 drops of methyl alcohol to 3 c.c. of water in a test-tube. Make a spiral of copper wire that will easily slip into the tube. Heat the wire until red hot and plunge it into the solution. Re- peat this several times. Cool the liquid, add 1 drop of 0.5% resorcinol solution, and with a pipette run in a bottom layer of 5 c.c. of concentrated sul- phuric acid. A red zone develops. Why is for- maldehyde produced by this procedure? This is used as a test for small quantities of methyl alcohol. ALDEHYDES 151 Acetaldehyde (ethanal, aldehyde), CH 3 -CHO, can be obtained in similar manner as formaldehyde by the oxidation of ethyl alcohol vapor, induced by heated platinum. The oxidation is generally effected, however, by the use of sulphuric acid and sodium or potassium dichromate, as described in the experiment below. Acetaldehyde boils at 20.8 and has a specific gravity of 0.780 at 20. Acetaldehyde can be changed into the polym- ers, paraldehyde, a liquid boiling at 124, and metaldehyde, a solid. Both have the formula (CH 3 -CHO) 3 . It is supposed that the difference in their structural formulae is a stereomeric dif- ference (see p. 214), that is, a difference in the arrangement in space of a CH 3 group in relation to the rest of the molecule. Paraldehyde is a hypnotic. Aldehyde molecules can be made to fuse together, forming a " condensation " product, aldol. Zinc chloride will effect this change: O H 2CH 3 CH -* CH 3 CH CH C It has been suggested that the production of starch and sugar by plants is due to condensation and polymerization of formaldehyde, the latter being synthesized from C02 and EbO. A sugar can be made from formaldehyde by condensation under the influence of lime-water (see p. 232). EXPERIMENTS. Preparation. (1) Mix in a large flask 100 c.c. of water and 30 c.c. of C.P. H 2 S0 4 . 152 ORGANIC CHEMISTRY Fit a cork having two holes, one for the bent tube connecting with a condenser, the other for a drop- ping funnel. Have the tip of the dropping fun- nel about 3 cm. above the liquid. Connect with the condenser, and place the receiving flask in ice-water. Heat the flask over wire gauze to the boiling-point. Now add through the funnel, in a slow stream, a solution of sodium dichromate (100 gm. of dichromate dissolved in 100 c.c. of water, FIG. 20. and mixed with 53 c.c. of alcohol). Remove the flame as soon as distillation is well started. If vapor passes through uncondensed, slacken the stream. If aldehyde ceases distilling, heat again with the flame. When all of the solution has been added, redistill the distillate. Save a portion of the crude distillate for making the aldehyde tests given below. In redistilling tilt the condenser upward, as shown in the diagram. Circulate through it water heated to 30, using a reservoir or large funnel. Connect the condenser with a drop- ALDEHYDES 153 ping funnel, which dips into the ether in the first wash-bottle. Put 25 c.c. of dry ether into each wash-bottle. As aldehyde will not condense at 30 , while most of the alcohol and water will, only aldehyde passes into the ether, which absorbs it. Keep the ether bottles in a bath of ice-water. When the aldehyde seems to have all passed over, trans- fer the ether to a beaker, which is placed in a freezing- mixture. Now bubble into it ammonia gas (se- cured by heating NH 4 OH in a flask), which has been dried by passing through a tower of soda-lime. A mass of white crystals of aldehyde ammonia will finally appear. Filter, wash the crystals with ether, and let them dry. From this product pure alde- hyde may be obtained by dissolving some of it in an equal weight of water, adding 3| times as much 50% H2S04, and then distilling. Put some of the crystals in a sample bottle, hold the bottle obliquely, bottom up, and fill with ammonia gas; cork and seal with sealing wax. Na 2 Cr 2 7 +4H 2 S0 4 = 3O +Cr 2 (S0 4 )3 +4H 2 0, CH 3 -CH 2 OH+0=CH 3 -CHO+H 2 0, CH 3 CHO +NH 3 = CH 3 NH (2) Aldehyde tests, (a) Add a little of the crude distillate to 5 c.c. of dilute Fehling's solution in a test-tube; boil until Cu 2 O is precipitated. (6) Add another small portion to a few cubic centimeters of ammoniacal AgNO 3 solution in a 154 ORGANIC CHEMISTRY perfectly clean test-tube; and heat gradually. A mirror of silver is deposited. (c) To 1 c.c. of dilute rosaniline (fuchsin) solution add a solution of sulphurous acid until almost decol- orized. Add some aldehyde solution and shake, a violet-red color appears. Schiff's reagent is very convenient to use for this test. 1 Chloral (trichloraldehyde), CC1 3 -CHO, is a chlor- ine derivative of acetaldehyde. It is produced by passing dried chlorine gas into absolute alcohol for several days. Aldehyde and HC1 are the first products of the chlorination. The final product X)C 2 H 5 is chloral alcoholate, CCls CH\ , an addi- ^ tion compound of chloral with alcohol. Chloral is liberated from this by the action of concentrated sulphuric acid. Chloral is an oily liquid, boiling at 97.7 and hav- ing a specific gravity of 1.512 at 20. It gives the aldehyde reactions. When it comes into contact with water it forms chloral hydrate crystals. / H Chloral hydrate, CCl 3 -Cr-OH, is believed to X OH have two hydroxyls attached to the same carbon atom, contrary to the general rule. It may be considered an addition compound of the aldehyde with water. One reason for believing that a typical 1 Prepare the reagent by saturating with S0 2 gas a solution of 2.2 gm. of rosaniline in 10 c.c. of water. Cork tightly and let it stand until light yellow or colorless. Dilute with 200 c.c. of water and keep in a dark-colored bottle well stoppered. ALDEHYDES 155 CHO group is not contained in it is the fact that it does not give the fuchsin test. Chloral hydrate is extremely valuable as a medicine, being used as a hypnotic. It is very soluble in water and in -alcohol. It melts at 57. Alkaline solutions decompose both chloral and chloral hydrate to chloroform and formic acid: CC1 3 CHO +KOH = CC1 3 H +HCOOK. (Potassium formate) EXPERIMENTS. (1) Try the aldehyde tests (see acetaldehyde) with a solution of chloral hydrate. (2) Warm a few cubic centimeters of chloral hydrate solution; after adding NaOH, notice the odor of chloroform. (3) Boil a few cubic centimeters of chloral hydrate solution; then test part of it with AgNOs; it gives no precipitate. Now add some zinc powder to the original solution and boil two minutes. Filter; test the filtrate with AgN0 3 ; it gives a white pre- cipitate of AgCl. The zinc decomposes water; the nascent hydrogen produced takes chlorine from the chloral hydrate, forming HC1 (which com- bines with the zinc) . (4) To 2 gm. of chloral hydrate in a dry test-tube add 5 c.c. of C.P. H^SO*, and warm gently while shaking. An oily liquid (chloral) separates as a top layer. Cool the tube to room temperature, and add 5 c.c. of chloroform which is free of alcohol and water. Draw off the top layer with a dry pipette, and allow the chloroform to evaporate; the residue in the dish will take up moisture from 156 ORGANIC CHEMISTRY the air, until finally chloral hydrate crystals are formed. Chloral Substitutes. Many derivatives of chloral have been synthetized with the object of correcting the tendency which chloral hydrate has to depress the circulation. Such are: Butyl-chloral hydrate (croton chloral), CH 3 CHC1 - CC1 2 CH(OH) 2 . Chloralformamide, (chloralamide) , /OH CCl3 - CH 0+H 2 0, C a H 8 0/ the resulting body being acetic anhydride. For practical purposes acetic anhydride may be prepared by acting on acetyl chloride with anhydrous sodium acetate, thus: C 2 H 3 OOiNa! +NaCl. C 2 H 3 Cll C 2 H 3 It is a fluid giving off a suffocating vapor. Added to water, it sinks to the bottom of the vessel, but gradually becomes reconverted into acetic acid. Its readiness to re-form acetic acid causes it to attack the hydroxyl group of alcohols and other hydroxyl compounds, one of the acetyl groups becoming thereby attached in place of the OH group, thus: C 2 H 5 |OH OC3EJ = C 2 H 5 OOC 2 H 3 +C 2 H 3 OOH. JL~QX^ (Ethyl acetate) (Acetic acid) \)C 2 H 3 Like acetyl chloride, it may therefore be em- ployed for ascertaining whether a substance con- tains hydroxyl not in carboxyl, and if so, how many such groups it contains (see p. 206). 170 ORGANIC CHEMISTRY (3) There remains for us to find out how the acetyl radicle C2H 3 O is composed. A clue to this is fur- nished by the observation that methane, CBU, and a carbonate are obtained by heating anhydrous sodium acetate with soda-lime (see exp., p. 120): C 2 H 3 OONa+NaOH =Na 2 C0 3 +CH 4 . This must mean that the two carbon atoms are of different value and that one of them exists in com- bination with hydrogen as methyl, CH 3 . Further corroboration of this is furnished also by the fact that the three H atoms which belong to the methyl group can be separately replaced by chlorine atoms, thus forming the substitution products mono-, di-, or tri-chloracetic acid: C 2 H 3 - OH + C1 2 = C 2 H 2 C10 - OH +HC1, C 2 H 2 C10 OH +C1 2 = C 2 HC1 2 OH +HC1, C 2 HC1 2 OH +C1 2 = C 2 C1 3 OH +HC1. The resulting substitution products retain the acid properties of acetic acid, such as the power of form- ing ethereal salts, anhydrides, etc. The chlor- acetic acids are much stronger than acetic acid, and the acid power increases with the number of chlorine atoms. (4) If we represent acetic acid as containing a methyl group, its formula must be written CCH 3 OOH, COCH 3 OH, or CH 3 COOH: which of these is correct? The valence of carbon prevents C of CH 3 from having more than one linking to the rest of the molecule; and for the other C to satisfy FATTY ACIDS AND ETHEREAL SALTS 171 its valence, it is necessary that it be linked to both oxygen atoms as well as to C of CH 3 ; therefore the structure must be CH 3 COOH. Further evidence that the group COOH does actually exist in acetic acid is given by the following observations: (a) The formation of sodium acetate by treating sodium methyl with CO 2 : CH 3 Na+C0 2 =CH 3 COONa. (6) The result of electrolysis of acetic acid. The cation H' is liberated at the cathode; the anion CH 3 COO' passes to the anode, where it is liberated as CO 2 and ethane (the two methyl (CHs) groups from two molecules having united). (5) By synthesis, as shown by the equations: CH 4 +Br 2 = CH 3 Br +HBr. CH 3 Br +KCN = CH 3 CN +KBr. CH 3 CN+2H20=CH 3 COOH+NH3 (p. 256). EXPERIMENT. Take 2 gm. of acetonitrile (pre- pared as directed in the experiment under methyl cyanide, on p. 255) and mix with 10 c.c. of 60% KOH in a small flask. Attach the flask to an upright (reflux) condenser. Heat for forty-five minutes. Note the ammonia escaping from the top of the condenser. Neutralize the resulting fluid with HC1 and test for acetic acid (see previous experiments) : CH 3 CN +2H 2 = CH 3 - COONH 4 , CH 3 COONH 4 +KOH = CH 3 COOK +NH 3 +H 2 O 172 ORGANIC CHEMISTRY THE CAUSE OF THE RELATIVE STRENGTHS OF ACIDS (AND BASES) It is important to understand what it is that con- stitutes the strength of an acid or alkali. This obviously cannot be gauged by titration with indicators: a normal solution of any acid will be neutralized by an equal volume of a normal solution of any alkali, and yet such acids as HC1, H 2 S04, etc., are far more reactive are stronger, in other words than such acids as acetic, lactic, etc. This difference in strength is explained by the fact that only a certain fraction of any acid or alkali is effect- ive, the value of this fraction being proportional to the strength of the acid or alkali. The effective fraction of an acid is that portion of it which becomes ionized. In solution, acids ionize into a cation of hydrogen or hydrion (which being charged with + electricity is often called the positive ion) and an anion of the rest of the molecule (see p. 66). In the case of solutions of strong acids a much greater proportion of acid ionizes in this way than in the case of an equimolecular solution of weak acids. We may therefore state that the active acidity of a solution of an acid depends on the concen- tration of the hydrogen ions. In the case of bases, e.g., KOH and NEUOH, dissociation in solution into cations of the metal or its equivalent (K,NBU) and into anions of hydroxyl occurs. It is the concentration of the hydroxyl ions (hydroxions) which determines their strength (cf. Amines, p. 260). FATTY ACIDS AND ETHEREAL SALTS 173 In a solution of HC1, for example, there exist: (a) undissociated HC1, (6) cations of H', and (c) anions of Cl'. A solution of acetic acid contains (a) undissociated CH 3 -COOH, (6) cations of IT, and (c) anions of CHsCOO'. The amount of (a) in the two cases will be very different, there being much less dissociation in the case of acetic acid than in the case of hydrochloric acid. In every acid, therefore, there must exist a certain proportion be- tween the undissociated and the dissociated por- tions. This will, of course, vary at different dilu- tions, for it will be remembered that dissociation increases with dilution (see p. 68). Since it is known that the electrical conductivity of a solu- tion depends on the amount of dissociation of the electrolyte dissolved in it, we may obtain a value for this proportion by measurement of electrical conductivity. In decinormal HC1 solution 91% of the molecules are ionized, as compared with 1.3% in decinormal acetic acid. In decinormal NaOH solution 84% of the molecules are ionized, but only 1.4% in decinormal NBUOH. (Consult the tables, p. 451). ETHEREAL SALTS. ESTERS. Corresponding to the salts of inorganic chemistry there are derivatives of organic acids in which the hydrogen of carboxyl is replaced by some hydro- carbon radicle. Thus ethyl acetate has the formula CH 3 COO-C2ll5, from which it is seen that the two constituent radicles are linked together through an oxygen atom as in the ethers (see p. 132). On this 174 ORGANIC CHEMISTRY account such compounds are usually called ethereal salts, or more briefly esters. In a looser sense, com- pounds of mineral acids with organic radicles, as ethyl nitrate, C 2 H 5 ONO 2 , and ethyl sulphate, (C 2 H 5 ) 2 S04, are included in this group; but since such as these have been considered elsewhere, we shall study at present only those salts in which organic acids are in combination. Inorganic salts are immediately formed when solu- tions of an acid and a base are mixed, for, both of these being ionized, the hydrogen ion of the acid immediately unites with the hydroxyl ion of the base to form water : (B- +OH') +(H- +Z') = (B- +Z') +H 2 CM (Base) (Acid) (Salt) Esters are, however, not thus readily formed, for the reacting hydroxide, being an alcohol, is not ionized, but remains as a molecule, and on this the acid only slowly acts: R - OH + (H- +Z') = R Z +H 2 0. (Alcohol) (Acid) (Ester) Inorganic are distinguished from ethereal salts not only in their ease of formation but also in their dissociability in solution, the former being usually entirely dissociated in solution, the latter not at all so. In this connection it is of great importance to point out that salts of organic acids with metals do undergo dissociation in solution, and to about equation will serve as an example of how ions are represented in a reaction. FATTY ACIDS AND ETHEREAL SALTS 175 the same extent as inorganic salts. Thus in a solution of ethyl acetate there are no free ions, whereas in one of sodium acetate dissociation into Na* and CH 3 COO' ions occurs. Mass Action. One of the notable illustrations of mass action is ester formation. The formation of an ethereal salt when an alcohol and an acid are directly mixed, although slow, yet proceeds until a balance between the four constituents is established (i.e., between acid, alcohol, salt, and water). This is because the reaction is a reversible one; in other words, whenever a slight excess of water comes to exist in the mixture, it decomposes the ester into the acid and alcohol, thus: CH 3 COOC 2 H5+HOH ? CH 3 COOH+C 2 H 5 OH. Such reversible reactions are often represented in equations by two arrows in place of the sign of equality. The mixture comes to a point of equilibrium when 0.669 part of a gram molecule of ester is pres- ent, provided we started with one gram-molecule of both acid and alcohol. At the beginning of the reaction the mass action of both alcohol and acid is most marked, forcing ester production, the re- verse action being very slight. As ester and water accumulate, ester formation slows up and the reverse action begins to figure in the reaction, until finally the mass action of the water to cause hydrolysis is as pronounced as that of the alcohol and acid to cause esterification. The equilibrium is not really static; for the action and the reverse 176 ORGANIC CHEMISTRY action are going on constantly to an equal degree, thus maintaining a balance. If a gram-molecule of both the ester and water are mixed, hydrolysis occurs, but apparently ceases when the same equilibrium point as for esterifica- tion is reached. In this case also the equilibrium mixture contains about two-thirds of a gram-mole- cule of ester and water, and one-third of a gram- molecule of alcohol and acid. The amount of ester thus formed depends on the relative amounts of acid and alcohol present and not on the temperature. With a given amount of alco- hol an increase in the amount of acid increases the yield of ethereal salt, and, conversely, the same is true with a given amount of acid when more alcohol is used. Since the progress of the formation of the above ester can be followed by titrating the residual acid, the reaction has been extensively employed in studying the laws of mass action. The fundamental law of mass action states that the product of the number of gram-molecules per liter of the substances on the one side of the equa- tion, divided by the product of these on the other side, is equal to some constant. In the case of the above reaction we have therefore the equation: C acidxC alcohol -= ^ = constant, C ester xC water where C represents gram-molecules per liter of the reacting substances. It will be evident that if we increase C acid while C alcohol remains constant, then C ester must FATTY ACIDS AND ETHEREAL SALTS 177 increase, which leads us to the conclusion that if enough acid is added, all the alcohol will become converted into ester, or, conversely, that if more alcohol is added, the acid remaining constant, the same will be true. For example if one gram- molecule of acetic acid and eight gram-molecules of ethyl alcohol interact, they come to equilibrium when 96.6% of a gram-molecule of ethyl acetate is formed. Temperature does not affect the constant to any marked degree, so that it does not influence the ultimate amount of ethereal salt produced. On the other hand, it greatly influences the rate of reaction, i.e., the time that it takes before the condition of chemical equilibrium is reached. Thus a rise in temperature increases the velocity of the reaction (as a rule the rate doubles for each increase of ten degrees in temperature). At 55 cane sugar is hydrolyzed by acids about five times as fast as at 25. By studying different alcohols and acids, it has been found that if equimolecular amounts of acid and alcohol be used, the limit of esterification varies only slightly; 1 but the rate is much greater for such acids as acetic than it is for such as ben- zoic, and for primary than for secondary alcohols. The amount of ester produced can be greatly 1 For example the per cent of a gram-molecule of ester formed by some alcohols and acids is as follows: Acetic acid+methyl alcohol 67.5, benzoic acid+methyl alcohol 64.5. Acetic acid +ethyl alcohol 66.9, benzoic acid -fethyl alcohol 67. Acetic acid +amyl alcohol 68.9, benzoic acid +amyl alcohol 70. 178 ORGANIC CHEMISTRY increased by removing the water formed during the reaction, and in some cases this can be accom- plished. By removing the ethereal salt as it is formed (e.g., by distillation or crystallization), much higher yields can also be obtained (see exp., p. 181). Preparation of Ethereal Salts. The more usual methods for preparing ethereal salts are the follow- ing: 1. By heating a mixture of the acid and alcohol with sulphuric acid: ethylsulphuric acid is first formed and then reacts with the acid, sulphuric acid being re-formed (cf. ether, p. 134), thus: (a) C 2 H 5 |OH+H .HS04 = C 2 H 5 -HS04+H 2 0. (6) C 2 H 5 i^HS^+|[loOCCH3 = C 2 H 5 OOC CH 3 +H 2 S0 4 . 2. By heating a mixture of the acid and alcohol with hydrochloric acid gas: an acid chloride is probably first formed, which then reacts with the alcohol : (a) CH 3 COJOH +H|C1 =CH 3 CO Cl +H 2 0. (6) CH 3 CO|a +H|OC 2 H 5 = CH 3 COO - C 2 H 5 +HC1. 3. Or the second stage of this reaction (6) can be itself used for the production of ethereal salts by treating an alcohol with an acid chloride or an anhy- dride of an acid. In this latter manner the acetyl or benzoyl (see p. 359) derivatives of many sub- stances can be produced, and these, being readily FATTY ACIDS AND ETHEREAL SALTS 179 purified, are extensively prepared for purposes of identification. The addition of sodium hydroxide accelerates this reaction in the case of benzoyl compounds (see p. 359). 4. By treating a silver salt of an acid with an alkyl halide (as iodide) ; CH 3 COO|Ag+I|C2H5 =CH 3 COOC 2 H 5 +AgI. Properties. Esters in a pure state are stable; in watery solution they slowly decompose into acid and alcohol, the decomposition being greatly ac- celerated by boiling with water and by the action of acids or bases. Hydrolysis most readily occurs with those esters which are easily formed; thus methyl acetate is more readily formed and is more easily hydrolyzed than ethyl acetate. Many esters have pleasant odors, often simulating those of fruits; for instance, isoamyl acetate has an odor resembling pears. On this account some of them are used as artificial fruit essences (see p. 187). Ethereal salts include the neutral fats (see p. 203). The two most important ethereal salts of acetic acid are methyl and ethyl acetates. Prepared by the general methods described above, both these bodies are liquids with pleasant odors. Ethyl acetate is commonly called acetic ether. From a biochemical standpoint the acceleration which acids induce in the hydrolysis of esters is of interest, partly because a method for the quanti- tative determination of the acid in gastric juice is based on it, and partly because it typifies catalytic 180 ORGANIC CHEMISTRY action , which is the means by which enzymes pro- duce their actions. Enzymes have a much more powerful action than other catalysts. Catalysis is defined as consisting in acceleration of reactions, which would take place without the cata- lyzer, but more slowly. (Some catalytic agents cause retardation of reactions.) Neither the acid molecule nor the ions enter into the chemical reac- tion. When a chemical agent enters into the reac- tion and is recovered, as sulphuric acid in ether production, it is a pseudo-catalyst. If equimolecular quantities of different acids be added to similar quantities of methyl acetate, it will be found that the acceleration of hydrolysis produced varies greatly with the acid employed. HC1 and HNOs produce about the greatest accelera- tion, whereas the commonest organic acids have only a feeble influence; thus the accelerating influ- ence of oxalic acid is only 19% and of acetic only 0.4% of that of HC1 (see table in Appendix, p. 452). Now it has been found that the electrical conduc- tivity of dilute solutions of the acids is directly proportional to their accelerating (catalytic) power, which leads us to the conclusion that the catalytic power depends on the amount of dissociation which the acids undergo; in other words, on the number of hydrogen ions existing in the solution (see p. 172). By this means, therefore, we have a practical method for gauging the relative strengths of acids (see p. 184). Further, if we add dilute solutions of varying con- centrations of the same mineral acid to methyl FATTY ACIDS AND ETHEREAL SALTS 181 acetate it will be found that the rate of hydrolysis is proportional to the strength of acid added. It is important to note that this law holds only for dilute solutions (less than decinormal) of strong acids and not at all for weak acids. By comparing the amount of hydrolysis of methyl acetate that occurs when a known quantity of acid is added, with the amount occurring in a similar solution of methyl acetate having an unknown quantity of the same acid, an estimate can be made of the amount of acid actually present in the latter. In this comparison the two solutions must of course be kept at the same temperature and the action allowed to proceed for the same length of time (see exp. below), EXPERIMENTS. (1) Put into a medium-sized flask 10 c.c. of alcohol and 10 c.c. of C.P. H 2 S0 4 . Use a three-hole cork; by one hole suspend a dropping funnel, by another connect with a condenser, and insert a thermometer so that its bulb is in the liquid. Heat until the liquid is at 135, then begin running in slowly by the dropping funnel a mixture of 80 c.c. of alcohol and 80 c.c. of glacial acetic acid, keeping the temperature of the mixture constant at about 135. Regulate the inflow of acid alcohol to correspond approximately to the rate of dis- tillation. Wash the distillate in the receiving flask with small portions of saturated sodium car- bonate solution until the top layer is no longer acid to litmus. Separate with a separating funnel. Add to the acetic ether a cold solution of 20 gm. 182 ORGANIC CHEMISTRY of calcium chloride in 20 c.c. of water and shake. (The ester is soluble in 17 parts of water). Separate with the funnel. Put the ethyl acetate into a dry flask, add solid calcium chloride, cork, and let it stand a day or so. Redistill on a water bath, noting the boiling-point (77). Determine the specific gravity (0.905 at 17). (2) Determine the rate of hydrolysis of methyl acetate as influenced by different strengths of acid (HC1). Into each of two small flasks put 1 c.c. of methyl acetate measured accurately with a pipette; to one add with a pipette 20 c.c. of HC1 solution of known strength (say 0.4%); to the other add 20 c.c. of HC1 more dilute but of unknown concen- tration; cork each flask and shake. As quickly as possible titrate 5 c.c. of each mixture successively with decinormal NaOH, using phenolphthalein as an indicator. This gives the acidity of each at the beginning of the experiment. Cork the flasks tightly with rubber stoppers and keep them in an incubator at about 40 for three or four hours; then, after shaking and cooling, take 5 c.c. from each and titrate again. The increase in acid (due to liberation of acetic acid by hydrolysis) is found by deducting the initial titration from this second titration. The stronger solution causes the greater amount of hydrolysis. To calculate the exact strength of the unknown acid solution by com- parison with the known, we must find out the limit of hydrolysis for the known strength; to do this leave the flask containing this acid in the incubator for forty-eight hours, then titrate again. The FATTY ACIDS AND ETHEREAL SALTS 183 titration at the end of this period, less the initial titration, gives an acid value called A] this is the number of cubic centimeters of decinormal acetic acid that can be liberated by hydrolysis of the methyl acetate by 0.4% HCl. Now we can reckon the per cent of HCl in the other solution in the following manner: Find the value of the constant / A \ in the formula C=log ( = for each solution, but call the constant of the known solution C f . The observed increase in acid content during the three or four hours' incubation is X. Take a particular experiment. A known solu- tion (0.43435% HCl) gave A =24.9 (c.c.). The increase (after four hours) in the known solution was 12.1 (c.c.); therefore A -X= 24.9 -12.1 =12.8: With the unknown solution X = 7 (c.c.) , A -X = 17.9 : Now the per cent of HCl in the unknown f C of unknownX " of known / (per cent HCl in known). Therefore per cent = ' (0.43435) =0.21544. \.2o7o/ In this particular case the unknown was of exactly half the strength of the known solution. 184 ORGANIC CHEMISTRY The rate of hydrolysis bears a definite relation to the number of hydrogen ions present in the solu- tion. Therefore with dilute solutions of easily ionizable acids an accurate estimation of the quantity of acid present can be made by this method. Most organic acids furnish so few hydrogen ions (see p. 157) that their presence has practically no effect. In consequence, the method is available for determin- ing the per cent of HC1 present in gastric juice or stomach contents. It must not be forgotten, however, that the pres- ence of salts (as in stomach contents) can change the rate of hydrolysis from what it would be if only pure acid were present. EXPERIMENT 3. Determine the relative strength of several acids, repeating the procedure of experi- ment 2. Decinormal solutions of tartaric, oxalic, trichloracetic and hydrochloric acids give interest- ing results. Ethyl acetate may be used instead of methyl acetate. Make a third titration of acidity after hydrolysis has proceeded for at least a day. Compare directly the c.c. increase of decinormal acid in the various mixtures. This will give a rough idea of the relative H ion concentrations. OTHER FATTY ACIDS Propionic acid (propanoic acid), CHs-CH^-COOH, resembles acetic acid. It can be prepared by oxidation of propyl alcohol, by hydrolysis of ethyl cyanide, and by the action of CCb on sodium-ethyl. FATTY ACIDS AND ETHEREAL SALTS 185 In addition it can be made by reduction of lactic acid, thus: CH3-CHOH-COOH+2HI . = CH 3 - CH 2 COOH +H 2 +I 2 . The hydriodic acid furnishes nascent hydrogen, and this brings about reduction. Corresponding to chloracetic acids there are chlor- propionic acids. But the halogen may take the place of hydrogen either in the CH 3 group or in the CH2 group of propionic acid. It becomes neces- sary, therefore, to distinguish between these two positions in the molecule. This is done by using Greek letters, a and /?. In order to have a rule that will apply to all acids, no matter how many carbon atoms the acid may contain, it is necessary to count backwards from the carboxyl group: thus, the group next to the COOH is in the a posi- tion, the second group is in the position, and so on; for example, CH 3 - CHOI- COOH is a-chlor- propionic acid, CH 2 C1-CH 2 -COOH is p-chlor- propionic acid. Butyric acid CH 3 CH 2 - CH 2 COOH, is normal butyric acid. Isobutyric acid or methylpropanoic acid has the f or- mula >CH COOH. Normal butyric acid is fermentation butyric acid, and occurs in Lim- burger cheese, rancid butter, and sweat. It may be prepared by oxidation of butyl alcohol and by hydrolysis of propyl cyanide. Butter contains 186 ORGANIC CHEMISTRY about 6% of butyrin, which is the glycerol ester of butyric acid (see p. 200) ; the acid can therefore be obtained by hydrolysis or saponification of butter (see exp., p. 207). Microorganisms can cause fermentation of butter, with resulting hydrolysis of the ester (butyrin) and setting free of butyric acid. Butyric acid is soluble in water and vola- tile. Oleomargarine contains very little butyric or other soluble volatile fatty acids. On this account it can readily be identified by making an estimation of the volatile acids in the manner to be described later in an experiment (see p. 207). Butyric acid can also be made from cane sugar as follows: The sugar solution, acidified with tar- taric acid, is inoculated with sour milk: one variety of microorganisms in the latter " inverts " the sugar into dextrose and Isevulose; another variety ferments these monosaccharides, producing lactic acid; while a third variety converts the lactic acid into butyric acid: (Cane sugar) (Dextrose) (Laevulose) (Lactic acid) 2C 3 H 6 3 = CH 3 CH 2 CH 2 COOH +2CO 2 +2H 2 . (Butyric acid) Similar fermentation, with production of lactic and butyric acids, may occur in the stomach when the hydrochloric acid of the gastric juice is deficient in amount or absent altogether. The gases formed and H 2 ) cause the flatulence present in such FATTY ACIDS AND ETHEREAL SALTS 187 cases. Butyric acid has the peculiar disagreeable odor characteristic of rancid butter. The ethereal salt C 3 H 7 -COOC 2 H 5 , ethyl butyrate, resembles pineapple in odor. It is used as a flavor- ing material in place of pineapple juice. Valeric acid (valerianic acid), CH 3 - CH 2 - CH 2 CH 2 COOH, is the normal acid. Ordinary valeric acid, however, CH 3 v is isovaleric acid, ">CH CH 2 COOH. It / occurs in valerian root. Amyl valerate, CJETg-COOCsHn, smells like apple, and is therefore used as an apple essence. This is the ester of isoamyl alcohol with isovaleric acid. It has been used as a medicine. Of the other acids of the formic acid series, only those containing an even number of CH 2 groups are of importance. Capnric acid is CH 3 (CH 2 ) 4 COOH. Caprylic acid is CH 3 (CH 2 ) 6 COOH. Capric acid is CH 3 (CH 2 ) 8 COOH. Laurie acid is CH 3 (CH 2 ) 10 COOH. Myristic acid is CH 3 (CH 2 )i 2 COOH. Palmitic acid is CH 3 (CH 2 )i 4 COOH. Stearic acid is CH 3 (CH 2 ) 16 COOH. Arachidic acid is CH 3 (CH 2 )i 8 COOH. Behenic acid is CH 3 (CH 2 ) 20 COOH. Most of these occur in fats. The lowest acids are volatile with steam and soluble. The higher acids 188 ORGANIC CHEMISTRY are non-volatile and insoluble. The melting-point of palmitic acid is 62.6, and of stearic acid is 69.2. The calcium salt of monoiodo-behenic acid is a remedy called sajodin; it is used for administra- tion of iodine. CHAPTER XIII SECONDARY AND CERTAIN OTHER MONACID ALCOHOLS. KETONES SECONDARY ALCOHOLS AND THEIR OXIDATION PRODUCTS SECONDARY alcohols contain the group CHOH, as in CHs CHOH CH 3 , secondary propyl alcohol. None of the secondary alcohols is of any importance. When a secondary alcohol is oxidized an aldehyde is not formed, but a ketone: CH 3 CHOH CH 3 +O = CH 3 CO - CH 3 +H 2 or A ketone is in all essential points identical with an aldehyde, the only difference being that in the case of an aldehyde the oxygen atom is attached to a carbon atom at one end of the chain, while in a ketone it is attached to an inner carbon atom. Some ketones can be oxidized, but this involves splitting up the chain of carbon atoms. Some ketones give the fuchsin test (see p. 154), particularly 189 190 ORGANIC CHEMISTRY those that have CH 3 CO in the molecule. Many ketones form addition compounds with acid sul- phites and with hydrocyanic acid (cf. aldehydes). Phenylhydrazine reacts with ketones in the same manner as with aldehydes, forming hydrazones. Ketones do not polymerize, but they form condensa- tion products. The reaction of phosphorus pentachloride with ketones is similar to that with aldehydes: CH 3 CO CH S +PC1 5 = CH 3 CC1 2 - CH 3 +POC1 3 . No hydrochloric acid is produced, and a dichlor derivative is formed; therefore a ketone does not contain hydroxyl. The most important ketone is acetone. Acetone (dimethylketone or propanone) is the sim- plest ketone, its formula being CH 3 -CO-CH 3 . It is produced commercially by the dry distillation of calcium acetate at about 300: CH 3 C< * ~ =CH 3 -CO-CH 3 +CaC0 3 . It can also be obtained by oxidation of secondary propyl alcohol. Its synthesis from zinc methyl and acetyl chloride proves the structural formula for acetone. CH, CH 3 -CO-|C1_ J\CH 3 =2CH 3 -CO-CH 3 +ZnCl 2 . SECONDARY ALCOHOLS AND KETONES 191 Acetone is present in the urine under certain con- ditions, especially in severe cases of diabetes. It is a useful solvent. It is a liquid, boiling a t56.3 (corrected), with a specific gravity of 0.812 at 0. Nascent hydrogen converts it into secondary pro- pyl alcohol. It does not oxidize to an acid contain- ing the same number of carbon atoms, but to acetic and formic or carbonic acids. Acetone gives the iodoform test. EXPERIMENTS. (1) Make iodoform, using ace- tone instead of alcohol (see p. 130). The reactions involved are of the same nature as in the preparation of iodoform from alcohol; in this case the intermediate compound is triiodoacetone, CI 3 -CO-CH 3 . (2) Dissolve 2 c.c. of acetone in dilute H 2 S04,* add KMn(>4 solution until a pink color remains on warming. Filter, make the filtrate strongly acid with 20% H 2 S0 4 , and distill. Test the distillate for acetic acid (see p. 163). (3) Shake 5 c.c. of acetone with 8 c.c. of a saturated solution of sodium bisulphite; cool; crystals of the addition compound of acetone appear. Filter and wash. Save samples. Chloretone (chloroform acetone, trichlor-tertiary- /O H butyl-alcohol), CH 3 (Xj- CC1 3 , is an addition X CH 3 product of acetone. It is formed by the interaction of acetone and chloroform in the presence of an excess of KOH, It is a useful hypnotic. 192 ORGANIC CHEMISTRY Brometone, the corresponding bromine prepara- tion, produced from acetone and bromoform, is analogous to chloretone. As a remedy it is used instead of bromides. Ketone acids. Some acids contain both the car- bony! and carboxyl groups. Aceto-acetic acid, CH 3 -CO-CH 2 -COOH, typifies these, and is of importance, since it may occur in the urine (see p. 218). Pyruvic acid (pyroracemic acid) is another ketone acid of importance. Its formula is CH 3 -CO-COOH. It shows a strong tendency to polymerize. Tertiary alcohols, when oxidized, decompose into compounds containing fewer carbon atoms than the alcohol. The tertiary alcohols are of no importance. Little need be said of other monacid alcohols, except that most waxes contain esters of monacid alcohols having a large number of carbon atoms; for example : Ceryl alcohol, C26H 5 30H. Cetyl alcohol, CH 3 (CH 2 )i 4 CH 2 OH. Melissic alcohol, C 3 oH 6 iOH. In waxes some of the alcohol is not in ester com- bination, but free. Cetyl palmitate has been found in the fat of an ovarian cyst. Lanolin contains -some wax esters (see p. 211). Myricyl palmitate, C 3 oH 6 iOOC-Ci 6 H 3 i, is the chief constituent of beeswax, CHAPTER XIV DIACID ALCOHOLS AND DIBASIC ACIDS DIACID ALCOHOLS DIACID alcohols contain two hydroxyl groups. They are comparable to Ca(OH)2. The simplest diacid alcohol, and the only one of importance, is glycol (ethandiol), CH 2 OH . The method of prep- CH 2 OH aration shows that both hydroxyl groups are not attached to the same carbon atom. Ethylene is produced from ethyl alcohol by heating the latter with an excess of sulphuric acid. The ethylene is saturated with bromine, forming ethylene bromide, in the manner described in the experiment (see p. 301). From ethylene bromide glycol can be obtained by the action of silver hydroxide: AOH CH 2 OH I " ...... = I +2AgBr. CH 2 jBr AglOH CH 2 OH Glycol is a colorless glycerol-like liquid, of sweet- ish taste. It boils at 195 and has a specific gravity of 1.128 at 0. It forms two classes of ethereal salts, according 193 194 ORGANIC CHEMISTRY to whether one or both hydroxyls are replaced. Similarly there are two sodium alcoholates of glycol: CH 2 ONa , monosodium glycolate, 1 and CH 2 OH CH 2 ONa , disodium glycolate. CH 2 ONa The oxidation products of glycol are numerous because of the presence of two primary alcohol groups. There are two aldehydes: ^>- | , glycolic aldehyde, and V_y- CH 2 OH JHO CHO I , glyoxal. CHO Oxidation of the first gives rise to glycollic acid, CH 2 OH ; this will be considered under hydroxy- COOH acids (see p. 212). Oxidation of glyoxal gives CHO , glyoxylic acid; this is really a dihydroxy- COOH acid, as will be seen later (see p. 219). These two acids are monobasic. Complete oxidation of glycol 1 Distinguish from the glycollates derived from glycollic acid (p. 213). DIACID ALCOHOLS AND DIBASIC ACIDS 195 results in the formation of a dibasic acid, oxalic acid, COOH GOGH* DIBASIC ACIDS The simplest is oxalic acid. The next members /COOH of the series are malonic acid, CH 2 succinic M^OOJci CH 2 COOH acid, | , and glutaric acid, CH 2 COOH /CH 2 COOH H2 \CH 2 COOH* General methods for the production of dibasic acids are (1) by hydrolysis of cyan-acids, (2) by oxidation of diacid alcohols, and (3) by oxidation of an Itydroxy-acid. The acids of the oxalic acid series show the same behavior as regards melting-points as do the acids of the formic acid series (see p. 158). COOH Oxalic acid, I , forms crystals containing two COOH molecules of water for each molecule of oxalic acid. The crystals readily effloresce. It may be prepared by oxidation of cane sugar with nitric acid. It was formerly made by heating sawdust with caustic potash and soda. After cooling the oxalate is dis- solved out of the mass, precipitated by slaked lime as calcium oxalate, and the separated oxalate is treated with sulphuric acid, so that the oxalic acid is set free. It is now made by heating together 196 ORGANIC CHEMISTRY potassium formate and hydroxide (and a little oxalate); and treating the product with sulphuric acid. Oxalic acid is one of the strongest of all organic acids, because its solution contains more hydrogen ions than the corresponding solutions of most other organic acids (see p. 172). As the number of C atoms interposed between the carboxyls of acids of this series is increased, acid power is decreased. When oxalic acid is heated, it first loses its water of crystallization, then decomposes into carbon dioxide, carbon monoxide, water, and some formic acid. If heated in the presence of glycerol, formic acid and carbon dioxide are formed (see p. 159). Sulphuric acid decomposes it to carbon monoxide, carbon dioxide, and water. Potassium permanganate in warm acid solution oxidizes it to carbon dioxide and water: 2KMnO 4 +5(COOH) 2 +3H 2 S0 4 = 10C0 2 +K 2 S0 4 +2MnSO 4 +8H 2 O. Oxalic acid forms two classes of salts, acid and COOH neutral. Acid potassium oxalate, \ , occurs COOK in plants, particularly sorrel. Ammonium, potas- sium, and sodium oxalates are soluble; all other oxalates of metals are practically insoluble. Cal- cium oxalate frequently occurs in the urine as a crystalline sediment. Oxalic acid is poisonous and has been used for suicidal purposes. DIACID ALOCOHLS AND DIBASIC ACIDS 197 EXPERIMENTS. (1) Preparation of oxalic acid. Heat 200 c.c. of HN0 3 in a large flask to 100. Set in a fume-closet and add 50 gm. of cane sugar. When the evolution of fumes has ceased, evaporate the acid mixture in an evaporating dish to about one third its original volume. Cool and collect the crystals. Recrystallize, using as little hot water as possible. (2) Heat some dry crystals of oxalic acid in a test-tube, loss of water of crystallization occurs, as shown by drops collecting on the cool part of the tube. (3) Decompose some oxalic acid with H2SO4; test the evolved gases for CO 2 (baryta water, as on p. 3) and CO (haemoglobin solution, as on p. 161). (4) To 5 c.c. of oxalic acid solution add a few drops of H 2 SO4, warm, then add potassium permanganate solution, it is decolorized. /COOH Malonic acid, CH 2 0+H 2 0. CK 2 CO/ (Succinic anhydride) Isosuccinic acid, however, when heated above 130, breaks up into propionic acid and carbon dioxide: /COOH CH 3 CH \ COOH = CH 3 CH 2 - COOH +C0 2 . It is, indeed, a general rule in organic chemistry that two carboxyl groups cannot remain attached to the same carbon atom at high temperatures, carbon dioxide being split off from one of the carboxyls. Alphozone (disuccinyl peroxide) is an organic peroxide (cf . acetozone p. 352) : HOOC(CH 2 ) 2 CO O O OC(CH 2 ) 2 COOH. It is an oxidizing agent, and is said to be antiseptic. CHAPTER XV TRIACID ALCOHOLS, FATS, AND SOAPS TRIACID ALCOHOLS CH 2 OH Glycerol (glycerine or propanetriol), | CHOH, is the . 2 OH only triacid alcohol of importance. Glycerol occurs in fats in combination with fatty acids and oleic acid, as glycerol esters of these acids. By hydrolyz- ing fats, glycerol is set free. This is accomplished commercially by heating fats (at 170-180) in a closed boiler or autoclave with water and lime. The lime combines with fatty acids, forming insolu- ble calcium salts, while the glycerol goes into solution. The calcium remaining in solution is precipitated with sulphuric acid. Glycerol is also a by-product of soap manufacture. The liquid left after the separation of hard soap, containing 4-5% of glycerol, is purified to remove salts and alkali. The dilute glycerol solution is then evapor- ated under diminished pressure, at as low a tem- perature as possible, until its specific gravity becomes 1.24. The crude glycerol is purified by combined steam and vacuum distillation. C.P. glycerol is prepared by treatment of distilled 199 200 ORGANIC CHEMISTRY glycerol with charcoal and distillation with steam in vacuo. Glyceryl butyrate or butyrin yields on hydrolysis glycerol and butyric acid, thus: CH 2 OOC C 3 H 7 CH 2 OH CH OOC - C 3 H 7 + 3H 2 = CHOH +3C 3 H 7 COOH. I I CH 2 OOC - C 3 H 7 CH 2 OH The other fats will be considered more fully pres- ently. Pure glycerol is a colorless, syrupy liquid, hav- ing a sweet taste. It boils at 290 and has a spe- cific gravity of 1.265 at 15. It is hygroscopic. Crystals of glycerol can be obtained by cooling to a low temperature (0); these melt at 17. It is volatile with water-vapor. It is useful as a solvent and as a preservative agent. One, two, or three of the hydroxyl groups can be replaced by chlorine to form mono-, di-, or trichlor- CH 2 C1 CH 2 C1 CH 2 C1 hydrin respectively: CHOH, CHOH, CHC1 A, CH 2 C1 CH 2 C1. If trichlorhydrin be heated with water to 170, it is hydrolyzed to glycerol. Glycerol can be obtained from ethyl alcohol by producing successively acetic acid, acetone, isopropyl alcohol, propylene, pro- pylene dichloride, trichlorhydrin, and, finally, glycerol : TRIACID ALCOHOLS, FATS, AND SOAPS 201 CH 3 CH 2 OH -> CH 3 COOH -> CH 3 CO CH 3 -> (Alcohol) (Acetic acid) (Acetone) ~> CH 3 CHOH CH 3 - CH 3 - CH CH 2 -> (Isopropyl alcohol) (Propylene) -> CH 3 CHC1 - CH 2 C1 -> CH 2 C1 CHC1 CH 2 C1 -> (Propylene dichloride) (Trichlorhydrin) - CH 2 OH CHOH CH 2 OH. (Glycerol) Glycerol forms salts with nitric acid. The tri- nitrate is nitroglycerine or nitroglycerol. It is a yellow, oily liquid, made by mixing glycerol with sulphuric and nitric acids. When the action has ceased, the mixture is poured into a large volume of cold water; the nitroglycerine separates as a CH 2 N0 2 I heavy oil. Its formula is CH N0 2 . It ex- CH 2 NO 2 plodes when suddenly heated or percussed, with the formation of nitrogen, nitric oxide, carbon dioxide, and water. Dynamite consists of infusorial earth or other material impregnated with nitroglycerol, and may contain as much as 75% of the latter. Nobel discovered that nitrocellulose (p. 247) will absorb nitroglycerine; a gelatinous mass being formed. Such explosives as cordite and ballistite are prepared in this way. Gelatin dynamite is prepared from resin, collodion gun-cotton, a little wood pulp, and nitroglycerol. Nitroglycerol is a strong poison, causing violent 202 ORGANIC CHEMISTRY headache and lowering of blood-pressure. In 1% alcoholic solution it is used as a medicine. 1 Tetranitrol is similar to nitroglycerol, chemically and phar- macologically. It is the tetranitrate of the tetracid alcohol erythrol. Glycerol forms glyceryl acetates when treated with acetic anhydride. This will be considered more fully under fats. COOH On oxidation glycerol yields gly eerie acid, CHOH, CH 2 OH COOH I and tartronic acid, CHOH. These are studied with COOH the hydroxy-acids (see pp. 219 and 221). Glycerophosphoric acid consists of one molecule of orthophosphoric acid combined with glycerol, CH 2 OH CHOH . CH 2 (H 2 P0 4 ). EXPERIMENTS. (1) Heat 1 c.c. of glycerol with 5 gm. of KHSO4 in an evaporating dish until it turns brown. Note the odor (acrolein) (see p. 302). The fumes will blacken a strip of paper that has been moistened with ammoniacal silver nitrate solution. (2) Repeat the same experiment, using lard or some other fat. Glycerol in combination also gives the acrolein test. (3) To a few cubic centimeters of NaOH solution 1 This is nitrite action (cf. amyl nitrite, p. 265). TRIACID ALCOHOLS, FATS, AND SOAPS 203 add CuSO* until a copious precipitate of Cu(OH) 2 is obtained; now add some glycerol and shake, a deep- blue solution results. FATS AND SOAPS Fats contain esters of glycerol with fatty acids and with the unsaturated acid, oleic acid. Only those members of the fatty acid series that contain an even number of CH 2 groups in then: formulae, occur in fats. Most fats are mixtures of palmitin (glyceryl tripalmitate), stearin (glyceryl tristearate), and olein (glyceryl trioleate). Olein is a liquid. Palmitin melts at 65, while stearin has the highest melting-point (about 72). The esters of low molecular weight, butyrin, caproin, caprylin, (these three are liquids), and caprin (melting at 31) are peculiar to butter. Mutton-fat contains a large percentage of stearin. Lard contains esters of lauric, myristic and linoleic acids, as well as the commoner esters. The softer fats contain less stearin and palmitin and relatively more olein. Physiologically, the fats of lower melting-point are more easily digested. CH 2 OOC-Ci 5 H 3 i Palmitin is CH OOC-Ci 5 H 3 i. CH 2 OOC-Ci 5 H 3 i CH 2 OOC-Ci 7 H 35 in is C] Stearin is CH OOC-Ci 7 H 35 . -OOC ' Cl 7 H 3 5 CH< 204 ORGANIC CHEMISTRY Mixed esters of glycerol can be obtained; some have been proved to occur naturally. CH 2 OOC-Ci 5 H 3 i CH-OOC.Ci 7 H 3 5 CH.2 OOC * Ci7ll35 is a mixed ester. The following mixed esters have been detected in beef and mutton fat : dipalmito-stearin, dipalmito- olein, palmito-distearin, and oleo-palmito-stearin. Butter contains glycerol esters of fatty acids that are volatile and soluble, namely, butyric, capric, caprylic, and caproic acids. Artificial butters (as oleomargarine) contain only very small amounts of these acids. Butter also contains esters of myristic, lauric and dihydroxystearic acids. It will be of interest to give the composition of the oils that are used most commonly in medicine: Cod-liver oil contains glycerides of palmitic, stearic, oleic, myristic, erucic, and two other un- saturated acids, also cholesterol. Croton oil contains tiglic, crotonic, formic, acetic, butyric, valeric, myristic, and lauric acids, besides palmitic, stearic, and oleic acids. Castor oil is composed chiefly of esters of ricinoleic and isoricinoleic acids, and contains also sebacic, stearic, and dihydroxystearic acids. Olive oil has olein to the extent of 70%, and con- tains also esters of palmitic and arachidic acids, and some phytosterol. TRIACJD ALCOHOLS, FATS, AND SOAPS 205 Fat Values. By determining certain analytical values 1 and by finding the melting-point and spe- cific gravity, a fat can generally be identified with the aid of the tables compiled for the purpose. The values referred to will now be briefly explained in order. (1) The Reichert-Meissl number indicates the amount of volatile soluble acid present in the fat. When butter or any other fatty substance is saponi- fied so as to free the fat acid and then distilled as described in the experiment below, the volatile acid in solution in the distillate can be readily estimated by titration. The Reichert-Meissl value is the number of cubic centimeters of decinormal acid contained in the distillate from five grams of fatty substance. (2) The acid number of a fat is found by titration of a solution of the fat in alcohol ether mixture with decinormal KOH, phenolphthalein being used as an indicator. This determines the amount of free acid present. The acid value is expressed as milli- grams of KOH required to neutralize the free acids in one gram of fat. (3) The total amount of acid present, free and combined, is indicated by the saponification number. A weighed quantity of fat (2-4 gm.) is saponified by heating it with an accurately measured quantity of alcoholic KOH solution of known strength (half normal); the resulting soap is diluted and titrated with half normal HC1 to find how much KOH X A very satisfactory book on this subject is Chemical Analysis of Oils, Fats, and Waxes, by J. Lewkbwitsch. 206 ORGANIC CHEMISTRY remains unneutralized. Then the amount in milli- grams of KOH combined with fatty acid as soap for each gram of fat taken is readily calculated; this is the saponification number. (4) The ester number of a fat represents the com- bined acid, being the saponification number less the acid number. (5) The iodine number estimates the amount of unsaturated acid (e.g., oleic) present. The iodine forms an addition compound with the acid (see p. 299). This value is expressed as the grams of iodine taken up by 100 grams of fat. (6) The acetyl number estimates the hydroxyl content. If glycerol is treated with acetic anhydride one molecule of acetic acid is produced for each hydroxyl group attached (see p. 169) : CH 2 |OH~~ """OC : CH51 CHOH+O CH 2 OH OC-CHs = CH 3 COOH +CH 2 - OOC - CH 3 CHOH CH 2 OH (Glyceryl monacetate) The reaction can be pushed until all of the hydroxyl groups are displaced, giving, as the products, glyceryl triacetate and acetic acid (three molecules of the latter for each molecule of glycerol). In a similar manner a fat which contains some hydroxyl groups can be " acetylated," and by estimating the acetic TRIACID ALCOHOLS, FATS, AND SOAPS 207 acid in combination with the alcohol, or acids of the fat, the hydroxyl content can be calculated. The acetyl number is the number of milligrams of KOH required to neutralize the acetic acid after hydrolysis of one gram of the acetylated fat. Par- tially hydrolyzed fat esters (e.g., a diglyceride) and hydroxy-acids are mainly responsible for this number. Such an acid is ricinoleic acid (p. 304) contained in castor oil, also dihydroxy-stearic acid, CH 3 (CH 2 )7(CHOH)2(CH 2 )7COOH, which is pres- ent in butter and in castor oil. The viscosity number (see p. 79) may be deter- mined for the purpose of detecting adulteration of olive oil, since the cheaper vegetable oils have a lower viscosity. EXPERIMENTS. (1) Compare the specific gravity of filtered butter with that of oleomargarine by suc- cessively putting a little of each in alcohol of specific gravity 0.926 at 15. There must be no air bubbles adhering to the fat. The oleomargarine will float (it having a specific gravity of about 0.918 at 15); the butter will either sink or remain suspended. (2) Reichert-Meissl number. Into a 300-c.c. flask put 5 gm. of filtered butter, 2 c.c. of 60% KOH solu- tion, and 20 c.c. of glycerol. Heat with a small flame, shaking to prevent excessive foaming. In about five minutes the water is boiled off and saponification is almost complete. Tip the flask and rotate to bring down any fat adhering to the walls. Heat again for a few minutes, then partly cool. The soap solution should be clear. Add 208 ORGANIC CHEMISTRY 90 c.c. of hot distilled water and shake until the soap is dissolved. Add 50 c.c. of 5% H 2 S04 and some zinc powder or small pieces of pumice. 1 Distill on a sand-bath. Collect 110 c.c. of distillate in a graduated flask. The distilling should be accom- plished in thirty minutes. Filter the distillate; take 100 c.c. of the nitrate with a pipette and transfer it to a beaker. Add a little phenol- phthalein solution and titrate with decinormal KOH until slightly pink. Multiply the number of cubic centimeters of alkali by 1.1; this gives the Reichert- Meissl number. For butter this value should not be less than 24. The experiment may be repeated with oleomargarine. (3) Acid number. Mix equal volumes of alcohol and ether; add phenolphthalein solution, then a drop or more of decinormal KOH until slightly pink. Now dissolve a weighed quantity of butter (5-10 gm.) in some of the ether-alcohol, and titrate with decinormal KOH to a faint pink, which remains after mixing. If the mixture becomes turbid during titration, warm it in a water bath (with no flame near it). When fats are decomposed with the aid of alkali, soap is formed. Hence the origin of the term saponification. In the strictest sense, saponifica- tion means the action of an alkali on an ester, the resulting products being an alcohol and a salt of the acid. Many use the word loosely as synony- mous with hydrolysis. 1 To prevent bumping. TRIACID ALCOHOLS, FATS, AND SOAPS 209 Soaps are metallic salts of the acids that occur in fats. Ordinary soaps are mixtures of potassium or sodium palmitate, stearate, and oleate. Potas- sium soap is soft soap, commonly called green soap. In many countries its yellow color is changed to green by the addition of indigo. It contains the glycerol that is freed by saponification. Sodium soap is hard soap, which has been freed of glycerol by " salting out " in the manner described in the experiment. Castile or Venetian soap, if genuine, is made from olive oil. It contains no free alkali. It is slightly yellow in color. Calcium, mercury, lead, copper, and many other metals form insoluble soaps. Cheap soaps are made with resin, sodium resinate acting similarly to true soap. The cleansing action of soap is largely due to hydrolytic dissociation of the salts in dilute soap solution. This dissociation can be demonstrated as follows: Add phenolphthalein to a concentrated soap solution, and only a slight red appears; now dilute with a large quantity of water, and a decided red develops (for effect of dilution on dissociation, see p. 68). The lather also aids mechanically in removing dirt. Sodium oleate is the most soluble of the salts of soap, and hydrolyzes the least. The hydrolyzed stearate and palmitate furnish colloidal particles. Various substances adsorb to these par- ticles, facilitating their removal in the washing process. This explains why vaseline can be removed by first treating the vaseline with a fat, and then using soap ; the vaseline is adsorbed. 210 ORGANIC CHEMISTRY The free alkali of soap solution probably acts to some extent to saponify the grease on the surface to be washed; while the sodium oleate acts to emul- sify the fat. Saponification, emulsification, and adsorption are all of them factors in the cleansing process. Experiments. (1) Put into a flask about 10 gm. of lard or tallow, add 5 c.c. of 60% KOH and 50 c.c. of alcohol; attach an upright air condenser tube, and boil moderately. After boiling half an hour test by shaking a drop of the fluid with half a test-tube of water; if no oily drops separate out, saponification is complete. Dilute with 50 c.c. of hot water. While hot add an equal volume of saturated solution of NaCl. Sodium soap will separate as a top layer and finally solidify. (2) To same soap solution add hydrochloric acid. Free fatty acids separate and rise to the top. Collect the fatty acids on a filter, wash thoroughly with water, press between filter paper, and crystallize from hot alcohol. (3) Make insoluble soap by treating same soap solution with calcium chloride solution (calcium soap), with lead acetate (lead soap), copper sulphate, and solutions of other metallic salts. Explain " hardness " of water. In a soap solution at least part of the soap is in the colloidal state; a concentrated solution made with the aid of heat gelatinizes on cooling (hydrogel). The colloidal behavior of the solution is said to TRIACID ALCOHOLS, FATS, AND SOAPS 211 be due in large measure to hydrolytic dissociation of the salt, the relatively insoluble product going into colloidal solution. Dried soap swells when soaked in water. Lanolin is a fat-like substance prepared by purify- ing wool grease. It contains about 25% of water and will take up more water until it holds 80%. It is more closely related to waxes than to fats, since by saponification its esters yield monacid alcohols, such as ceryl alcohol. In addition to esters it con- tains free acids, free alcohols, cholesterol, and isocholesterol. CHAPTER XVI HYDROXY-ACIDS Hydroxy-acids contain both alcohol (OH) and acid (COOH) groups. The acid properties, however, are more marked than the alcohol properties. They are not acid alcohols, but hydroxy-acids, and may therefore be defined as acids in which a hydrogen atom attached to one of the carbon atoms is re- placed by hydroxyl. They are often called oxy- acids. The simplest possible hydroxy-acid would be hydroxy-formic acid, H- COOH -> HO- COOH. (Formic acid) (Hydroxy-formic acid) It will be observed that this is identical with the hypothetical carbonic acid, ^COs. The lowest typical hydroxy-acid is hydroxyacetic /OH acid, CH2 and S l y collic acetate, ' .OOC.CHs COOH ' Glycollic acid is found in green grapes and else- where. It forms needle crystals, melting at 80. It is a stronger acid than acetic acid. When heated Distinguish glycollates from the glycolates derived from glycol (p. 194). 214 ORGANIC CHEMISTRY in an atmosphere of carbon dioxide at 210, it combines with itself, losing water, and thus forms an anhydride called glycollid: .2 < C OHH1 OC /CH CH 2 CH 2 +2H 2 0. COO This has neither alcoholic nor acidic properties. Hydroxypropionic acids are commonly called lactic acids. Just as there are two monochlorpro- pionic acids, a and /3, so there are an a-hydroxy- propionic acid and a /3-hydroxypropionic acid. The j8 acid, /OH CH/-- CH 2 COOH, shows by its reactions that it is related to ethylene (see p. 300). It is therefore called ethylene lactic acid. It is unimportant. Lactic acid proper, a-hydroxypropionic acid, /OH CH 3 -CH^--COOH, is known in three forms as isomers. As with some of the amyl alcohols (p. 144), these isomers have identical structural formulae. Isomerism of the kind to be described now is called stereoisomerism. 1 1 Stereochemistry (stereos meaning solid) treats of those chem- ical and physical phenomena that are supposed to be caused by the relative positions in space occupied by the atoms within the molecule. HYDROXY-ACIDS 215 To understand this it is necessary to conceive of the atoms of the molecules as being arranged in space, and not on one plane as in ordinary formulae. The main carbon atom is thought of as being placed in the center of a tetrahedron, at the apex of each solid angle of which is situated an atom or group. Models of wood or pasteboard will be helpful in understand- ing this. To represent a-lactic acid, -write the groups CH 3 , OH, H, and COOH at the corners of the tetrahedron, thus: OH CH 3 COOH Try the effect of interchanging these groups in all possible ways. It will be found that two and only two different arrangements are possible. 1 Further, when the tetrahedron representing one combination is held before a mirror, the image in the mirror will be seen to correspond exactly to the other possible arrangement. This is true only in the case of com- pounds that would be represented as having four different groups at the corners. If* two of these 1 The truth of this statement can be most clearly shown by writing down the various possible arrangements and then marking off those that are identical. The student will be interested in observing that his hands are mirror images of each other. 216 ORGANIC CHEMISTRY groups are the same, only one arrangement is possible and stereoisomerism cannot occur. The tetrahedron representing lactic acid is unsym- metrical as regards the kind of groups present; its central carbon atom is therefore said to be an asym- metric carbon atom. It has been found that com- pounds containing an asymmetric carbon atom rotate the plane of polarized light. 1 Dextrolactic acid rotates it to the right, laevolactic acid rotates it to the left. As represented by models, laevolactic acid is the mirror-image of dextrolactic acid. Ordi- nary lactic is also an a-lactic acid, but it does not affect polarized light; it is optically inactive. It has been shown to consist of equal quantities of dex- trolactic and Isevolactic acid molecules; such a substance is called racemic. 2 The two constituent acids of racemic acid neutralize each other in their action on polarized light. Optically active substances that have a physiological action may show a dif- ferent degree of action on the animal organism *A few optically active organic compounds have been pre- pared which contain asymmetric atoms other than carbon. Certain quaternary bases have an asymmetric N atom, as C,Hs\ \ C 6 H 5 .CH 2 -N The pentavalent N atom has been conceived of as at the center of a pyramid. 2 Racemic substances are not always mixtures; thed, ^-mixtures might better be called conglomerates. The racemic, properly speaking, contain the two active molecules in some sort of molecular combination (cf. tartaric acid). HYDROXY-ACIDS 217 according to whether it is the d or I isomer that is acting (see nicotine, p. 430, atropine, p. 432, and cocaine, p. 433). Dextrolactic acid (d-lactic acid) is also called sarcolactic acid, because it occurs in flesh. It is present in beef extract. It is also the product of fermentation of dextrose by the Micrococcus acidi paralactici. Its salts are laevorotatory. Laevolactic acid (/-lactic acid) is obtainable by fer- mentation of dextrose by the Micrococcus acidi Icevo- lactici. f Racemic lactic acid (d-, Mactic acid) is a syrupy 15 liquid having a specific gravity of 1.2485 at -^-. It is stronger than most organic acids, and much stronger than propionic and ethylene lactic acids, to which it is related. It is the product of ordinary lactic acid fermentation. When milk sours, milk- sugar becomes converted into lactic acid by micro- organisms : =4C 3 H 6 O 3 . (Lactose) (Lactic acid) No matter in what way lactic acid is artificially produced by synthesis, the synthetic acid is always racemic. The law of probability as applied to chemical synthesis calls for the formation of just as many molecules having the dextro-arrangement as the laevo. It can be shown that d } Mac tic acid contains dextrolactic acid by growing the mold Penicillium glaucum in a solution of d, /-ammonium lactate, because the mold destroys the Isevolactic 218 ORGANIC CHEMISTRY acid. On the other hand it may be shown to con- tain Isevolactic acid by fractional crystallization of a solution of strychnine lactate, since the Isevo- lactate crystals are formed first. When heated to 150 in dry air, lactic acid changes to an anhydride called lactid (cf. glycollic acid, p. 214). Hydriodic acid reduces lactic acid to pro- pionic acid (see p. 185). EXPERIMENT. In a retort mix 5 c.c. of lactic acid, 10 c.c. of water, and 5 c.c. of concentrated H^SO*. Connect with a condenser. Heat with a smoky flame. Test the distillate for aldehyde (see p. 153) and for formic acid (see p. 160) : CH 3 CHOH GOOH = CH 3 CHO +H COOH. /3-Hydroxybutyric acid (/3-oxybutyric acid), CH 3 - CH(OH) CH 2 COOH, is pathologically of importance, since it may occur in the blood or urine, especially in diabetes. It is laevorotatory, its specific rotation (p. 245) being -24.12. It will be noticed that the ketone acid acetoacetic acid (/3-ketobutyric acid) corresponds to the above alcohol acids, just as ketones correspond to second- ary alcohols (see also p. 192) : CH 3 CHOH -CH 2 - COOH (cf. CH 3 CHOH - CH 3 ) CH 3 .CO-CH 2 -COOH (cf. CH 3 -CO-CH 3 ). /3-Hydroxybutyric acid can be readily oxidized to acetoacetic acid by hydrogen peroxide. HYDROXY-ACIDS 219 T -Hydroxy-acids are very unstable. They readily split off water to form anhydrides called lactones, thus: CH 2 (OH) CH 2 CH 2 COOH (7 -Hydroxybutyric acid) o- (Butyrolactone) The carbon chain is closed by a linking through oxygen. It is, however, not a typical closed chain. The presence of hydrogen ions acts catalytically to hasten the formation of the lactone, and it is supposed that the H ions of the 7-hydroxy acid itself have this action, causing autocatalysis. When boiled with caustic alkalies, the lactones form salts of the corresponding hydroxy-acids; thus lactones give a " saponification value." This fact must be borne in mind in examining unknown substances supposed to be fats or waxes. Dihydroxymonobasic acids are illustrated by glyceric acid, CH 2 OH CHOH. COOH. Glyoxylic acid, which has been previously men- tioned (p. 194), while classed as an aldehydic acid, is according to some chemists a dihydroxy-acid, because it holds a molecule of water inseparable from it (cf. chloral hydrate): 220 ORGANIC CHEMISTRY /H COOH C\ +HOH = COOH % OH or CH(OH) 2 -COOH. It is a reducing agent like aldehydes (as chloral hydrate). EXPERIMENTS. (1) To 20 c.c. of a strong solu- tion of oxalic acid add 1 gm. sodium amalgam; when evolution of gas has ceased, filter. The filtrate is a dilute solution of glyoxylic acid: COOH COOH - +H 2 0. COOH CHO (Oxalic acid) (Nascent (Glyoxylic acid) hydrogen) (2) To 5 c.c. of albumin solution (egg-white solution) add 5 c.c. of the glyoxylic acid solution, then 5 c.c. of concentrated H 2 S0 4 ; mix and heat gradually; a bluish-violet color is obtained, due to trytophan contained in the protein molecule. Most proteins give this test. An example of a trihydroxy-acid is cholic or cholalic acid, (CH 2 OH) 2 [C 20 H 31 (CHOH)] COOH. The constitution of the C 2 oHsi portion of the formula is unknown. This acid is important phys- iologically, since its combinations with glycin and with taurin, glycocholic and taurocholic acids, are the most valuable constituents of bile. Glycocholic acid has the formula: C 20 H 3 i(CHOH) (CH 2 OH) 2 - CO HN - CH 2 COOH. HYDROXY-ACIDS 221 Taurocholic acid is [C 20 H 3 i(CHOH) (CH 2 OH) 2 CO NH- (CH 2 ) 2 S0 3 H. Glycuronic acid is an aldehydic tetrahydroxy-acid, CHO-(CHOH) 4 -COOH, the arrangement of the secondary alcohol groups being the same as in dextrose. It is formed by the animal body from dextrose when it is needed to combine with abnormal substances, such as drugs or indol. It is excreted in the urine as paired glycuronates; these are Isevorotatory. By heating with dilute acid, gly- curonic acid is set free; this is dextrorotatory. It is closely related to monosaccharides, differing only in the change of the CH 2 OH group to COOH. The free acid and some of its combinations reduce alkaline copper solutions (like other aldehydes), more particularly after prolonged heating of the mixture; so that occasionally a mistake may be made in concluding that a reducing urine contains sugar. It is not fermentable. It gives the pentose reactions (see p. 230). Monohydroxydibasic Acids. COOH Tartronic acid, CHOH, has been supposed to take I COOH part in the physiological synthesis of uric acid, particularly in birds (see p. 290). Malic acid is hydroxysuccinic acid, CH(OH) COOH 222 ORGANIC CHEMISTRY It is contained in sour fruits, e.g., apples and cherries. Agaric Acid is used as a remedy. Its formula is Ci 4 H 2 7(OH)(COOH) 2 . Dihydroxydibasic Acids. COOH | OH Mesoxalic acid, C\ , is the third exception to | X OH COOH the rule that two hydroxyls cannot be attached to the same carbon atom, chloral hydrate and gly- oxylic acid being the two other exceptions. Tartaric acid is dihydroxysuccinic acid, CH(OH) COOH CH(OH) COOH* Here there are two asymmetric carbon atoms (see p. 216) in the molecule. This fact causes a species of stereoisomerism, that is more difficult to under- stand than that of lactic acid. With the aid of models it can be clearly understood. Arrange pairs of tetrahedra as shown in the diagram. It will be noticed in the case of dextro- and Icevo- tartaric acids that the groups, OH and OH, H and H, are connected by straight lines and are on opposite sides of a line connecting the centers of the tetra- hedra; they are diagonally opposite, while the COOH groups are vertically opposite each other, both being at an angle of the tetrahedron that points for- HYDROXY-ACIDS 223 ward. As with the models for lactic acid, these models for active tartaric acids cannot be made identical by turning the model about. Place the Ia3votartaric model before a mirror; the image corresponds to dextrotartaric acid. Racemic tartaric acid when in solution is a mixture of equal quantities of dextro- and Ia3vo-tartaric acids (cf. racemic lactic acid). 1 There is, however, an- other inactive tartaric acid which cannot be sepa- Dextro-tartaric acid. Laevo-tartaric acid. FIG. 22. Meso-tartaric acid rated into optically active acids. This is mesotartaric acid. By studying the diagram above, or a model, it will be seen that the neutralization of optical properties is an inner molecular one, since the arrangement of the groups on the top corresponds to that of Isevotartaric acid, while the arrangement at the base corresponds to that of dextrotartaric. 2 1 The racemic tartaric acid crystals, however, are represented by the formula 4C 4 H 6 6 +2H 2 O. 2 It will further be noted that an acid of this variety is not possible in the case of lactic acid. 224 ORGANIC CHEMISTRY Racemic and mesotartaric acids differ widely in melting-point and solubility. Ordinary tartaric acid is dextrorotatory. It is contained in grape-juice as potassium bitartrate or acid tartrate, HOOC(CHOH) 2 COOK. When wine is produced this salt separates out because of its relative insolubility in dilute alcohol. This crude tartar, or argol, is called cream of tartar when puri- fied. It is used in the manufacture of the best baking-powders. Baking-powder is a mixture of sodium bicarbonate and some acid salt, which on FIG. 23. being dissolved liberates carbon dioxide from the bicarbonate. Tartaric acid is obtained from potas- sium bitartrate by precipitation as calcium tartrate, from which the acid is liberated by using the proper amount of dilute sulphuric acid. It forms large crystals, melting at 170. On heating further it turns brown and gives off an odor like caramel. It is easy soluble. Dextrotartaric acid can be converted into racemic acid by boiling with an excess of strong sodium hydroxide solution. The two methods given for separating racemic lactic acid into the active acids HYDROXY-ACIDS 225 are applicable also to racemic tartaric acid. Pasteur discovered a third method which is very interesting. By slow evaporation (below 28) of a solution of sodium ammonium racemate, two classes of crystals can be obtained, which from their appearance might be called right-handed and left-handed crystals (see Fig. 23). The crystals are mirror-images of one another. These can be picked out mechanically; one set furnishes dextrotartaric acid, the other Isevotartaric acid. Rochelle salt is sodium potassium tartrate, CH(OH) COONa | +4H 2 0. CH(OH) COOK This has the power of holding Cu(OH)2 in solu- tion, as in Fehling's solution. It is used as a cathartic. Tartar emetic is potassium antimonyl tartrate, CH(OH) COOK CH(OH) COO(SbO). It is used as a medicine. EXPERIMENTS. (1) Heat some tartaric acid in a test-tube, stirring it with a thermometer. Note the melting-point. Remove the thermometer and continue heating. The acid turns brown and emits an odor like scorched sugar. 1 1 Certain other acids act in the same way, particularly citric, malic,' tannic, and gallic. 226 ORGANIC CHEMISTRY (2) Prepare tartar emetic. Dissolve 5 gm. of potassium acid tartrate in 50 c.c. of water, add 4 gm. Sb 2 0s and boil. Filter and test some of the filtrate for antimony with H 2 S. Set aside the rest of the filtrate to secure crystals by slow evaporation. (3) After reading a description of the polariscope 1 and its manipulation, determine the rotary power of a strong solution of tartaric acid. Monohydroxytribasic Acids. CH 2 COOH I Citric Acid, C(OH) COOH, is present in currants, CH 2 COOH gooseberries, and lemons. It forms large crystals (having one molecule of water of crystallization) and is easily soluble. Citrates are valuable medi- cines. Citrates redissolve Cu(OH) 2 which has been precipitated by NaOH (cf. Rochelle salt in Fehling's solution). Other hydroxyacids that are mentioned else- where are dihydroxystearic acid (p. 207) and ricino- leic acid (p. 304). 1 A good description can be found in Cohen's Practical Organic Chemistry, also in Mathews' Physiological Chemistry. CHAPTER XVII CARBOHYDRATES- AND GLUCOSIDES CARBOHYDRATES THIS class of compounds is of very great im- portance, since it includes sugars and starches. The name carbo(n)hydrates calls attention to the fact that the hydrogen and oxygen in their for- mulae have the same ratio as in the formula for water; 1 therefore a general formula often given for carbohydrates is C n (H 2 0) m . This, however, is misleading, for there 'are a num- ber of non-carbohydrate substances that conform to this formula, such as acetic acid, C 2 H 4 02, and lactic acid, CaHeOs. Carbohydrates may be defined as including mono- saccharides and those more complex substances that yield by hydrolysis simply monosaccharides. All monosaccharides contain in their formulae a CO group, either in an aldehyde group or as the ketone group, and have also an alcoholic hydroxyl attached to each of the other carbon atoms. This may be condensed to the statement: mono- saccharides are aldehyde or ketone derivatives of polyhydroxylic alcohols. There are four classes of carbohydrates, namely, 1 It should be pointed out in this connection that the term hydrate as applied to alkalies is inaccurate, e.g., NaOH is so- dium hydroxide, not a hydrate. 227 228 ORGANIC CHEMISTRY monosaccharides, disaccharides, trisaccharides and poly saccharifies. 1 Monosaccharides are the simplest carbohydrates. From the linking of fcwo monosac- charide molecules, disaccharides result. A trisac- charide contains in its molecule three monosac- charide molecules. Polysaccharides have complex molecules that can be resolved into many mono- saccharide molecules. Monosaccharides and disac- charides act as very weak acids, but their H ion concentrations are extremely low. MONOSACCHARIDES According to the number of carbon atoms present, monosaccharides are called dioses, trioses, tetrpses, pentoses, hexoses, heptoses, octoses, and nonoses. Aldoses are those containing an aldehyde group, while ketoses are those having a ketone group. CH 2 OH GlycoLaldehyde, I , may be considered a diose. CHO Glycerose can be obtained by mild oxidation of glycerol (or lead glycerate); it is a mixture of an aldehyde and a ketone, and since each contains three carbon atoms, they are trioses: CH 2 OH CH 2 OH CH 2 OH CHOH -> CHOH + CO CH 2 pH CHO CH 2 OH (Glycerol) (Glyceric aldehyde) (Dihydroxyacetone) (Glycerose) 1 These are also called monosaccharoses, disaccharoses, tri- saccharoses, and polysaccharoses. CARBOHYDRATES AND GLUCOSIDES 229 CH 2 OH CHOH Tetrose, | , can be obtained by polymeriza- CHOH CHO tion of glycol aldehyde. A ketose tetrose also occurs. The chief pentoses are d-arabinose and [Z-xylose. The following formulae represent their isomeric rela- tion: CH 2 OH CH 2 OH HO C H HO C H I I HO C H H C OH H C OH HO C H I I CHO CHO (d-arabinose) (Z-xylose) Arabinose is obtainable by boiling gum-arabic with dilute acid. Xylose can be obtained by similar means from bran or wood. Racemic arabinose is sometimes present in the urine as an abnormal constituent. Several ketose pentoses are known. On account of having three asymmetric C atoms, four main arrangements and the mirror images of these are possible, so that eight aldose pentoses are obtainable. Seven of these are known at present. Both arabinose and xylose reduce Fehling's solu- tion and form osazones with phenylhydrazine (the 230 ORGANIC CHEMISTRY nature of the osazone reaction will be explained presently). Neither is fermented by pure yeast. They give certain color reactions, which will be illustrated in the experiment below. If a pentose is boiled with strong HC1, an aldehyde having a closed chain (furfurol) is produced : HOjCH GHJOHJ TT-PTT P/S I O^M <-\|OH|. CHO=CH C -CHO+3H 2 N 0|H \ ./ (P^ntoaer"" f{ ' (Furfurol) Most of the monosaccharides thus far considered have not been found in natural products. Several methyl derivatives of monosaccharides occur in glucosides, as digitoxose, CeH^O^ a di- methyltetrose, digitalose, CyHuOs, a dimethyl- pentose, and rhamnose, C 6 Hi20 5 , a methyl pen- tose. EXPERIMENT. Pentose test. To 2 c.c. of water in a test-tube add 2 c.c. of HC1 and warm. Add phloroglucin, a little at a time, as long as it dissolves. Now add 1 c.c. of arabinose solution, and heat until a red color is obtained; examine at once with a small spectroscope, when an absorption band between the d and e lines will be seen. Heat until a precipitate forms, add some amyl alcohol, and shake; the alcohol becomes colored and gives the same spectroscopic appearance as above. CARBOHYDRATES AND GLUCOSIDES 231 The hexoses are the sugars of prime impor- tance. The chief ones are dextrose, galactose, and laevulose; the first two are aldoses, while the last is a ketose: CH 2 OH 1 CH 2 OH 1 CH 2 OH 1 HO C H 1 HO C H 1 HO C H 1 HO C H H C OH HO C H H C OH H C OH H C OH HO C H CHO Dextrose (d-glucose) ) HO C H CHO (d-galactose) i, )H 2 OH (Lsevulose (cMructose)) The aldoses have four asymmetric C atoms, there- fore eight main arrangements of the secondary alco- hol groups together with their mirror images make sixteen aldose hexoses possible. Twelve of these have been studied. d-Mannose differs from d-glucose only in the arrangement of the fourth secondary alcohol group. The mirror image aldoses are the Z-hexoses and are Isevorotatory. The chemical name for laevulose is fructose, and it is called d-fructose because the arrangement of its secondary alcohol groups is the same as in d-glucose. Six ketose hexoses are known, the only one of importance being Isevulose. Two methyl hexoses have been prepared. Condensation of the aldehyde and ketone trioses 232 ORGANIC CHEMISTRY in glycerose results in the production of a ketose, d, I fructose, thus : CH 2 OH CH 2 OH CHOH CHOH CHO+HCHOH = CHOH CO CHOH I I CH 2 OH CO (Glyceric aldehyde) (Dihydroxyacetone) (Glycerose) CH 2 OH (Ketohexose) The condensation of formaldehyde induced by weak alkali yields the same product. All the synthetic sugars are optically inactive when produced by purely chemical means. Physiologists believe that in the animal body glycerol (from fat) may be converted into a hexose, at least under certain circumstances. Dextrose is the aldehyde of the hexacid alcohol sor- CH 2 OH toly (CHOH) 4, and can be converted into the latter CH 2 OH by reduction. Dextrose can be oxidized to the COOH dibasic acid saccharic acid, (CHOH) 4. The alcohol C OOH dulcitol, a stereoisomer of sorbitol, can be oxidized to galactose, and this aldehyde rApnosaccharide can CARBOHYDRATES AND GLUCOSIDES 233 COOH I be oxidized further to mucic acid, (CHOH)4. Sim- COOH ilarly there are alcohols and acids corresponding to the other hexoses. These alcohols and acids have the same arrange- ment of the secondary alcohol groups as the mono- saccharides to which they are related. Glycuronic acid (p. 221) is a monobasic acid, having the same arrangement of the CHOH groups as d-glucose, the aldehyde group also being present. There are certain proteins that contain a carbo- hydrate derivative combined with the protein mole- cule proper; such are called glucoproteins. This combined sugar has been found in most cases to CH 2 OH (CHOH) 3 be an aminohexose, generally glucosamine, \ , CHNH 2 CHO sometimes galactosamine. Z-Xylose is found in combination in nucleoproteins. The sugar group in protein may be detected by certain color reactions (see exp. below). The question of the possibility of the formation of dex- trose from proteins other than glucoproteins is of very great physiological importance. The chemistry of the problem will now be briefly considered. Proteins readily split up into amino- acids (see p. 267). When we reason on purely chemical grounds, 234 ORGANIC CHEMISTRY we see that it is possible that amino-acids containing three or six carbon atoms can be converted into dextrose. Alanin can be changed to lactic acid, the latter to glyceric acid, which can be reduced to glyceric aldehyde, and finally this can be converted into a dextrose-like sugar by aldol con- densation. Such a synthesis when carried out in the animal organism would undoubtedly result in production of dextrose, i.e., dextrorotatory glucose. It is quite likely that serin is also convertible into lactic acid and therefore into dextrose; CH 2 OH-CHNH 2 COOH, serin. CH 3 .CHNH 2 -COOH, alanin. CH 3 CHOH COOH, lactic acid. CH 2 OH CHOH COOH, glyceric acid. CH 2 OH CHOH . CHO, glyceric aldehyde. CH 2 OH (CHOH), CHO, dextrose-like aldose. The production of dextrose from alanin, glycocoll, aspartic acid and glutaminic acid in the animal body has been exper- imentally demonstrated, lactic acid being noted as an inter- mediate product. EXPERIMENT. To 1 c.c. of a strong solution of egg protein add a drop of saturated solution of a-naphthol in alcohol (acetone-free); then with a pipette add 1 c.c. of C.P. EbSO^ so that the acid does not mix, but forms a bottom layer. The greenish color at the zone of contact is due to the reagents ; let the tube stand until a violet ring forms. If the violet color does not appear, tap the tube so as to cause a slight mixing of the two layers. This is Molisch's test and is given by all carbohydrate- containing substances. CARBOHYDRATES AND GLUCOSIDES 235 Instead of the alcoholic solution a 10% solution of a-naphthol in chloroform may be used. General Reactions of Monosaccharides. They all reduce alkaline silver, .copper, and bismuth solu- tions, as do other aldehydes and some ketones (see p. 153). All form osazone crystals when treated with phenylhydrazine acetate (see exp. below). The reaction occurs in two stages; first the O of CO is substituted (as in hydrazones), then secondly the excess of phenylhydrazine removes two H atoms of the neighboring CHOH group, converting it to CO, and the latter reacts with phenylhydrazine. The osazone from Isevulose is identical chemically with that from dextrose, because Isevulose has the same arrangement of CHOH groups as dextrose, and the end CH 2 OH is changed to CO in this case. In similar manner d-mannose gives an osazone that is the same as glucosazone, Methylphenylhydrazine gives osazones with ke- toses only, and can therefore be used to detect the presence of Isevulose. Glucosazone has the formula, CH 2 OH (CHOH) 3 CN-NH-CeHs. C=N-NH-C 6 H 5 236 ORGANIC CHEMISTRY This can be converted by treatment with warm CH 2 OH (CHOH) 3 hydrochloric acid into glucosone, | When CO CHO glucosone is treated with nascent hydrogen (as by using zinc dust), fructose is formed. Thus we can convert an aldose into a ketose. Dextrose and galactoseare dextrorotatory; Isevu- lose is Isevorotatory. They all have a different rotary power when freshly dissolved from that which they show after allowing the solution to stand. This phenomenon is called mutarotation or multirotation. This has been explained by supposing a lactone-like linking in the sugar molecule so that the C of the alde- hyde group comes to hold H and OH. This C atom is now asymmetric and two stereoisomers become possi- ble, designated as a and /3. This has been investi- gated in the case of Z-arabinose, d-galactose, lactose and d-glucose. This will be illustrated by d-glucose: CH 2 OH CH 2 OH HO C H HO C H -C H H C OH H J.J. V_X ^ HO C ] H C OH HO C H a-d-glucose /3-d-glucose CARBOHYDRATES AND GLUCOSIDES 237 The a variety, immediately after preparing a solution, has a specific rotation (p. 245) of 110, the |8 variety 19. On standing each solution changes and both finally come to a specific rotation of 52.5; in the one solution a partly changes to j8, and in the other solution /? partly changes to a. The two come into equilibrium when 40% of the glucose is a and 60% in the case of concentrated solutions. The change from the one form of glucose to the other is believed to take place through an intermediate form, this being not a lactone but the hydrated aldehyde, CH 2 OH(CHOH) 4 CH(OH) 2 . There is supposed to be a trace of this present in the equilibrium mixture, thus explaining the response of the sugar solution to aldehyde tests. Maltose is believed to be made up of two a-d-glucose molecules, and isomaltose of two 0-d-glucose molecules. These hexoses are fermented by yeast, the main products being alcohol and carbon dioxide. /-Glu- cose does not ferment, possibly because the optically active enzyme fits only the rf-form. In making a test for reducing sugar (dextrose, Isevulose, pentoee, or lactose) in the urine, reduction of Fehling's solution is not sufficient, for the urine may reduce this reagent slightly after the administration of chloral hydrate, camphor, menthol, thymol or antipyrin because these bodies are excreted in gly- curonic acid combination (see p. 221). While the bismuth test excludes many non-saccharine substances (uric acid and creatinin) that reduce Fehling's solution, it may yet be positive with urine after the administration of antipyrin, salol, tur- pentine, kairin, senna, rhubarb, benzosol, sulphonal, or trional. The phenylhydrazine test is the most delicate and the most positive. The fermentation test, if positive, is generally con- 238 ORGANIC CHEMISTRY elusive. If lactose or a pentose alone be present, fermentation will not occur. These can be distinguished by a special pentose test, and in the case of lactose by increase in dextrotation after boiling with dilute HC1 (hydrolysis). Lsevulose can be differentiated from dextrose by the special ketose test and by laevorotation. Chloroform added to urine as a preservative gives reduction because heating it with alkali produces formic acid. Normal urine has a reducing power equivalent to 0.2% dextrose, but less than one-fifth of this is due to dextrose. Dextrose (glucose, grape sugar) is present in many fruits and plants, in honey, and in the urine of diabetic patients. Commercial glucose is made by boiling starch with dilute acid; it is used for making candies, cheap syrup, etc. This crude glucose con- tains dextrin. Pure glucose is crystalline ; if crystal- lized from water it contains a molecule of water of crystallization, but if crystallized from methyl alcohol it is anhydrous. It is not so sweet as cane sugar. Galactose is obtained from lactose, by hydrolysis of the latter. It ferments slowly. Laevulose (fructose, fruit sugar) is contained in many sweet fruits, in honey, and rarely in urine. It is difficult to crystallize. Its rotary power is greatly dependent on temperature and concentra- tion. Calcium forms a compound with Isevulose that is only slightly soluble. The corresponding glucose compound is easily soluble. EXPERIMENTS. (1) Prepare osazone crystals from dextrose and Isevulose as follows: To 10 c.c. of a strong solution of the sugar add 0.25 gin. of phenyl- CARBOHYDRATES AND GLUCOSIDES 239 hydrazine hydrochloride and 0.5 gm. of sodium acetate, heat in a boiling water bath for an hour, and cool. Examine the yellow crystals under the microscope. Collect the crystals on a filter, wash thoroughly with cold acetone or water acidulated with acetic acid, press between filter-paper, recrystallize from a little 80% alcohol, dry the crystals in a desic- cator, and later make melting-point determinations. 1 The osazones of the important sugars have the following melting-points : Dextrose I 204-205 Lactose 200 Maltose 206 (2) Ketose test. To 5 c.c. of laevulose solution add 5 c.c. of 25% HC1. Add a little resorcin and heat the mixture. A deep red color develops, and later a brown precipitate, which is soluble in alcohol. The alcoholic solution is red. (3) (a) Try the aldehyde tests (see p. 153) with dextrose solution. (6) To some dextrose solution add one-fifth its volume of alkaline bismuth reagent (4 gm. Rochelle salt and 2 gm. of bismuth sub- nitrate dissolved in 100 c.c. of 10% NaOH), and boil five minutes. On cooling a black precipitate separates out. 1 A quicker and more satisfactory way of securing osazone crystals is as follows: To 0.5 c.c. phenylhydrazine (base) add 0.5 c.c. glacial acetic acid; after mixing add 10 c.c. of the sugar solution, and heat in a boiling water-bath; glucosazone crystals appear in 5-10 minutes. For lact- and maltosazone, heat 20-30 minutes, then cool before examining. '240 ORGANIC CHEMISTRY Several heptoses and octoses and two nonoses are known, but they are unimportant. DISACCHARIDES These are the result theoretically of the union of two monosaccharide molecules, with the elimination of a molecule of water, cane sugar being a combina- tion of dextrose and Isevulose, lactose of dextrose and galactose, and maltose of two a-d-glucose molecules : By hydrolysis the constituent monosaccharides are easily obtained: Dilute mineral acids and ferments (invertases) bring about this hydrolysis, which is called inversion. Yeast produces an invertase that hydrolyzes maltose quickly and another that hydrolyzes cane sugar slowly, but none that has an effect on lactose. Therefore lactose does not ferment with yeast, while cane sugar and maltose do. Inversion by the action of dilute mineral acids is due to catalytic action of hydrogen ions, just as in the case of hydrolysis of esters (p. 180) (see appen- dix, p. 452). Maltose and lactose reduce alkaline copper and bismuth solutions; pure cane sugar does not. After inversion, however, cane sugar reduces these reagents. Therefore Fehling's solution can be used for quantitative estimation of all the sugars treated CARBOHYDRATES AND GLUCOSIDES 241 of in this chapter. 10 c.c. of Fehling's solution is reduced by 0.048 gram dextrose. 0.051 " Isevulose. 0.0676 " lactose (+H 2 0). 0.074 " maltose. 0.0475 " cane sugar (after conversion into invert-sugar) . A solution of copper acetate acidified with acetic acid (Barfoed's reagent) is not reduced quickly to cuprous oxide by disaccharides, but is so reduced by monosaccharides. Maltose and lactose form osazones with phenyl- hydrazine, each of these having a characteristic crystalline form and melting-point (see p. 239), while cane sugar forms no such combination pro- vided hydrolysis is guarded against. In order to explain the non-aldehydic action of cane sugar as shown by its behavior in these two re- actions, the following formula has been suggested for it : CH 2 OH CH 2 OH HO C H 242 ORGANIC CHEMISTRY Both the aldehyde and ketone groups are tied up by the linking together of their C atoms. The other disaccharides have the following for- mulae: Maltose. CH 2 OH -CH 2 HO C H C H H C OH HO C H H C OH a-d-glucose) HO C H C H H C OH i-H (d-galactose HO H C OH d-glucose) These disaccharides are all dextrorotatory. Mal- tose shows the greatest rotary power, lactose the least; maltose and lactose manifest multirotation. Lactose solution contains a and & lactose in equilib- CARBOHYDRATES AND GLUCOSIDES 243 rium; /3 lactose has the formula above but with the end group arranged as in jS-d-glucose. Invert- sugar is distinctly Isevorotatory, while the cane sugar from which it is produced is dextrorotatory; this is due to the fact that the Isevulose produced (invert- sugar is a mixture of equal parts of Isevulose and dex- trose) rotates polarized light more to the left than does dextrose to the right. The rotary power of maltose is decreased by in- version, while that of lactose is increased. Saccharose (cane sugar, beet sugar, sucrose), Ci2H 2 2On, is the most important of the sugars because of its use as food. It is contained in sugar cane, beets, the sap of certain maple trees, and in many other vegetables and plants. The method of commercial preparation of cane sugar is, in brief, as follows: The juice is obtained from the sugar cane by shredding and then crush- ing the cane between rollers. The sugar beet, how- ever, is cut into slices and these are soaked with successive portions of hot water, the sugar diffusing out of the beet pulp. The sugar extract is treated with lime (which removes acids and many im- purities), then with carbon dioxide (which removes the excess of lime), and is then evaporated in vacuum pans. On cooling, sugar crystallizes out. This crude sugar is dissolved, filtered through bone- black (animal charcoal), evaporated, and recrystal- lized. The syrup that is left is molasses. Cane sugar as sold is commonly called granulated sugar. Cane sugar forms large crystals when slowly crystallized; they are monoclinic prisms. It melts 244 ORGANIC CHEMISTRY at 160; at 210-220 it is converted into caramel with loss of water. It is extremely soluble, 100 gm. of water at 15 dissolving 197 gm. of sugar; this saturated solution has a specific gravity of 1.329. It forms saccharates with bases. Its rotary power is influenced somewhat by con- centration; it is lessened by presence of acids, alkalies or salts, but it is practically uninfluenced by temperature. Lactose (milk sugar), C^H^On+EbO, is the sugar contained in milk. It occasionally occurs in the urine of pregnant and nursing women. Cer- tain microorganisms convert lactose into lactic acid. When heated it forms lactocaramel, CeHioOs. Lactose is crystalline and contains a molecule of water of crystallization. It can be obtained as amorphous lactose, which is anhydrous. Lactose forms compounds with bases. Its specific rotation is not influenced much by concentration or temper- ature. Maltose, C^B^On+EbO, is the product of the action of the ferments diastase (in malt), ptyalin (in saliva), or amylopsin (in pancreatic juice) upon starch. It can also be obtained from starch by treatment with dilute mineral acids, the action of the acid being stopped at a stage before glucose is formed. It crystallizes in fine needles. Its specific rotation varies with concentration and tempera- ture. Isomaltose (gallisin) is distinguished from maltose in that it does not ferment with yeast, and that its osazone has a lower melting-point (150). CARBOHYDRATES AND GLUCOSIDES 245 EXPERIMENTS, (1) Produce osazone crystals from lactose and from maltose (footnote, p. 239). When the solutions have cooled, examine micro- scopically. Make melting-point determinations. (2) (a) Examine a 10% solution (10 gm. dissolved in enough water to make 100 c.c. of solution) of pure cane sugar with the polariscope (see p. 226). (6) To 50 c.c. of a 20% cane sugar solution in a 100 c.c. grad- uated flask add 1 gm. of citric acid, and heat in a boil- ing water-bath for 30 minutes. Cool, almost neu- tralize, and fill up to the mark. Examine this invert-sugar solution (corresponding in concentra- tion to the solution in (a) with the polariscope. 1 The specific rotation [a]D of the important sugars in 10% solution (at 20) when sodium light is used is as follows: Dextrose (anhydrous) +52.5 Lsevulose - 93.0 Maltose (anhydrous) +137.04 Lactose (+H 2 0) +52.5 Cane sugar + 66 . 54 Invert sugar - 20.2 Galactose + 81 .0 ( means rotation to the left.) (3) Test cane sugar before and after inversion (solutions of experiment 2, a and 6) with Fehling's solution. (4) Try the ketose test (see p. 239) on cane sugar. M 100 X rotation observed > For calculation, % sugar [a]Oxdecimeters tube length - 246 ORGANIC CHEMISTRY (5) Galadose test. To 10 c.c. of a strong solution of lactose add 3 c.c. of HNOs and boil for a few min- utes. Now evaporate on a water-bath to about 3 c.c. while stirring. Add 2 c.c. of water and cool. If no crystals of mucic acid separate out, let the material stand and examine after twenty-four hours. The trisaccharide mffinose, consists of d-fructose, d-glucose and d-galactose linked together as in saccharose, none of the CO groups being free. It therefore does not reduce nor give an osazone. Emulsin hydrolyzes it to cane sugar and galactose. Invertase of yeast hydrolyzes it, therefore it fer- ments. It gives the ketose test. Its specific rotation is +104, POLYS ACCHARIDES These have complex molecules, the empirical formula of each being an unknown multiple of Cellulose, (C 6 Hi 5 )^ or (Cel^C^OH^X of high molecular weight, is essential to all plants, being the basis of the woody fiber. Cotton-fiber, hemp, flax, and the best filter-paper are almost entirely cellulose. Ordinary paper is composed mainly of cellulose. Cellulose is affected by only a few chemical agents; concentrated acids and alka- lies and an ammoniacal solution of copper oxide (Schweitzer's reagent) are able to dissolve it. If unsized paper be treated momentarily with sulphuric acid, its surfaces become changed to amyloid, which renders the paper tough when dried. Parchment paper is made in this way. If a solution of cellulose CARBOHYDRATES AND GLUCOSIDES 247 in sulphuric .acid be diluted and boiled, dextrin and glucose are produced by hydrolysis of the cellulose. EXPERIMENTS. (1) Dissolve some scraps of filter- paper in a little cold concentrated B^SCU, dilute with 200 c.c. of water, and boil for an hour. Neu- tralize some of this hydrolyzed cellulose solution and test with Fehling's solution. (2) Immerse a piece of blotting-paper in 80% H2S04 for a moment only, transfer to a large beaker of water, and wash out the acid thoroughly. Allow the paper to dry out; it will be found to be tough. (3) Detection of lignin 1 in paper made from wood. Coat a sheet of cheap white paper with a solution of aniline in HC1; if it turns yellow, lignin is present. Esters of cellulose can be formed by the action of reagents that attack alcoholic hydroxyl groups (as acetic anhydride). When cellulose is treated with nitric acid in the presence of sulphuric acid, nitro-celluloses are formed, just as nitroglycerol is produced from glycerol. These range from mononitro- to trinitrocellulose. Guncotton (nitrocellulose, pyroxylin) is trinitro- cellulose. It is explosive. By dissolving gun- cotton in acetone a gelatinous mass is obtained; then on removing the solvent, the guncotton is left in such a physical condition that it burns and explodes more slowly. This substance is used in 1 A substance present with cellulose in wood; it is supposed to contain pentosans and aromatic bodies. 248 ORGANIC CHEMISTRY smokeless powders. The products of the explosion are nitrogen, hydrogen, carbon monoxide and dioxide, and water-vapor. The two lower nitrates are contained in celloidin. Collodion is a solution of these nitrates in a mixture of ether and alcohol. Celluloid is made by dis- solving them in camphor with the aid of a little alcohol. An artificial silk can be produced by means of trinitrocellulose, fine filaments being made and spun into thread. After being woven the nitrocellulose fabric is treated with a solution of calcium sulphide, which removes the N0 2 groups. Almost pure cellulose, resembling silk, is left. Artificial silk is pro- duced by two other methods, one of these, called the viscose method, is supplanting the others. Viscose silk is made from as pure cellulose as can be obtained from wood pulp. The latter is treated with NaOH solution and CS 2 , and is macerated for a considerable time. The cellulose solution is squirted through very fine openings into an acid bath which precipitates the cellulose as fibers. Large quantities of artificial silk are now produced. EXPERIMENT. Mix 5 c.c. of C.P. HNOs and 10 c.c. of C.P. B^SO*. When it is cool, immerse some absorbent cotton in the mixture for half a minute, then wash out the acid from the cotton with a large quantity of water, press out the water, and dry at room temperature. When dry, shake part of it with a mixture of ether and alcohol, pour the liquid into an evaporating dish and allow to evaporate. A syrupy liquid (collodion) is obtained, and later a glassy skin. Test the inflammability of another piece of the dry cotton, and compare with un- treated cotton. CARBOHYDRATES AND GLUCOSIDES 249 Starch (amylum), (CeHioOs)^, comprises a large part of all vegetable food. It exists in the plant as granules, having different forms and sizes in dif- ferent plants. Starch grains are spherocrystals, covered with a layer of specially modified starch substance which is more resistant to the action of water, ferments and chemical agents than the sub- stance within the grains. Starch and cellulose are probably synthesized by plants from formaldehyde by processes of conden- sation and polymerization. Ordinary starch is made from corn or potatoes. Starch is insoluble in cold water. When boiled, it apparently goes into solution or forms a gelatinous mass, according to the amount of water present. It is a colloidal solution containing also tiny masses in suspension. It is precipitated from solution by low concen- tration of alcohol, and by saturation with certain salts (as Na2S(>4 and NaCl). A dilute solution of boiled starch is readily hydrolyzed by ferments (diastase, ptyalin, etc.) and by platinum black (catalytic action) at a temperature of about 40. Dextrin is first formed, then maltose, while hydrolysis by boiling with dilute mineral acid carries the proc- ess further, the end product being glucose. Heat alone converts starch into dextrin; the crust on bread is mainly dextrin. Starch takes up iodine, probably by adsorption, thus forming a blue sub- stance; heat drives the iodine from this substance, so that the color is lost until the mixture becomes cool again. Natural starch contains two dif- 250 ORGANIC CHEMISTRY ferent materials, a soluble substance amylose (60-80% of the weight of the starch) and an insolu- ble substance, amylopectin, which gelatinizes with hot water. Amylopectin gives little color with iodine, while amylose gives a deep blue. Both are hydrolyzed by ferments. It is probable that there is a very large number of amyloses (stereoisomers). Dextrins are less complex bodies than starch. The intermediate substances between starch and maltose formed during digestion are, in the order of complexity, amylodextrins, erythrodextrins, achroodextrins, and maltodextrins. The first gives a blue color with iodine, the second a red or reddish brown (a mixture of erythro- and amylo-dextrins gives a bluish red color), while the simpler dextrins give no color test. Commercial dextrin is prepared from starch by means of heat. It forms a gummy solution, which is used for making labels. It is insoluble in alcohol. Most dextrins are precipitated by saturating their solutions with salts, such as ammonium sulphate and sodium sulphate. Most dextrins are precipitated by alcohol when the concentration reaches 75%; the lower dextrins require as much as 90% for precipitation. The dextrins are dextrorotatory, the (a)D being 192-196 for the higher dextrins. Acid hydrolyzes them to glucose. Diastatic ferments change them to maltose. Glycogen, (CeHioOs)^, resembles dextrin. It is present in animal tissues, mainly in the liver. The liver acts as a storehouse for carbohydrates, storing up in the form of glycogen the sugar that comes to CARBOHYDRATES AND GLUCOSIDES 251 it from the digestive organs, and then reconverting the latter into sugar as needed by the tissues. A substance has been found in certain vegetables resembling glycogen. Glycogen forms a colloidal solution, which is characteristically opalescent. With iodine it gives a reddish brown color. Its (a)D is +196.5. It hydrolyzes to dextrose. Di- astatic ferments form from it dextrins, and finally maltose. It is precipitated by 55% alcohol and by basic lead acetate. EXPERIMENTS. (1) Test solutions of starch, dex- trin, and glycogen with iodine solution. (2) Test them with lead subacetate solution. (3) Test them with Fehling's solution before and after hydrolyzing by boiling with dilute HC1. Gums contain polysaccharides similar to dextrin. Gum arabic (acacia) contains a pentosan, araban, (CsHsO^n which hydrolyzes to Z-arabinose. Gum tragacanth contains bassorin. Agar-agar is a pectin-like substance containing at least seven different carbohydrates, including some starch and cellulose. The most important constituent is gelose, a galactan, which can be hydrolyzed to galactose. GLUCOSIDES Natural glucosides are vegetable substances which can be split up by hydrolysis into a sugar (or sugars) and some other characteristic organic compound or compounds. Many of them are important medi- 252 ORGANIC CHEMISTRY cines. A large number of glucosides have been studied. The sugar derived from them is generally glucose. Phloridzin, C 2 iH 2 4Oio, is used to produce exper- imental diabetes in animals. It splits up into glucose and phloretin, Ci 5 Hi 4 5 (see also phloro- glucin, p. 348). Arbutin, Ci2Hi 6 7 , is a comparatively simple glucoside, hydrolyzing to dextrose and hydro- quinone. Gaultherin, CuHigOs, is a glucoside contained in the wintergreen plant; an accompanying ferment hydrolyzes it to dextrose and methyl salicylate. Salicin, CisHigOy, is used in medicine; it hydro- lyzes to dextrose and saligenin (p. 354). Its struc- /O-CeHnOs tural formula is C 6 H 4 < ^ TT ^ TT M^i 2 Uil Amygdalin, C 2 oH 27 NOii, is found in bitter almonds, peach-pits, etc. The ferment emulsin, as well as acids, hydrolyzes it to glucose, hydrocyanic acid, and benzaldehyde (see p. 351). Its structural formula is said to be: O CH(CHOH) 2 CH CHOH - CH 2 >CH (CHOH) 2 CH-CHOH-CH 2 OH. I. C 6 H 5 CH CN CARBOHYDRATES AND GLUCOSIDES 253 Digitalin, CasHseOi*, an active principle of digi- talis, hydrolyzes to dextrose, digitaligenin, C22H3o03, and digitalose, CrHuOs. Digitoxin, C 3 4H 5 40ii, the chief active glucoside of digitalis, yields by hydrolysis digitoxigenin, C22H 3 2C>4, and digitoxose, Cell 1204. Strophanthin, C4oH 6 60i9, from strophanthus, hydrolyzes to strophanthidin, C2?H38O7, methyl alcohol, mannose and rhamnose. Sinigrin, CioHi 8 NS2KOio, the glucoside of black mustard, by the action of a ferment present in the mustard splits up into mustard oil, dex- trose, and KHS04. In similar manner sinalbin, C3oH44N2S2Oi6, of white mustard yields dextrose, parahydroxytolyl mustard oil and, sinapin bisul- phate. Indican, CuHiyOeN, is the glucoside which is contained in those plants from which indigo is produced. It is a combination of glucose and indoxyl. The indican present in urine (p- 417) is a different compound. Saponins. A large number of glucosides are grouped together into this sub-class. They are non-nitrogenous and form solutions that foam on shaking (cf. soaps). Digitonin is a saponin contained in digitalis, C54H 9 2O28; it splits up into digitogenin, CsoH^sOe, and two molecules each of glucose and galactose. Artificial glucosides are simpler compounds; for example, a methyl glucoside of d-glucose has the CHs group attached to O of the aldehyde group of glucose. 254 ORGANIC CHEMISTRY EXPERIMENTS. (1) Try Molisch's test (see p. 234) on a solution of a glucoside. (2) Hydrolyze some glucoside solution by boil- ing with dilute H 2 S04, neutralize, and examine for sugar with Fehling's solution. CHAPTER XVIII NITROGEN DERIVATIVES. (ALSO PHOSPHORUS AND ARSENIC COMPOUNDS) NITROGEN DERIVATIVES THESE fall into four classes: (1) cyanogen derivatives, (2) substituted ammonias, (3) nitro compounds, and (4) nitrites. Cyanogen Derivatives. Organic cyanides can be prepared by treatment of alkyl halides with potas- sium cyanide, as C 2 H 5 |cf +K|CN = C 2 H 5 CN +KC1, (Ethyl chloride) (Ethyl cyanide) also by anhydrolysis (removal of water) of an acid amide (see p. 273), thus (see exp.): CH 3 CONH 2 = CH 3 CN +H 2 O. (Acetamide) (Methyl cyanide) EXPERIMENT. Into a dry 250-c.c. wide-mouth Jena flask (extraction flask) put 10 gm. of dry acetamide and add quickly about 15 gm. of phos- phorus pent oxide. Mix quickly with a dry rod. As soon as possible add 10 gm. more of the oxide as a top layer. Cork and connect with a condenser immediately. Heat with a small smoky flame. 255 256 ORGANIC CHEMISTRY Collect the distillate in a large clean test-tube. Shake the distillate with half its volume of water, then add small pieces of solid KOH until no more dissolves, keeping the solution cool with running water; the cyanide now separates as a top layer. Transfer to a narrow test-tube, and remove the cyanide carefully with a clean dry pipette. Use the product for synthesis of acetic acid (p. 171). The CN group of organic cyanides can be hydrolyzed to COOH; in consequence the alkyl cyanides are called acid nitriles; for example, CHs-CN is acetonitrile because acetic acid can be obtained from it (see exp., p. 171) : CH 3 CN +2H 2 O = CH 3 COOH +NH 3 (i.e., CH 3 COONH 4 .) HCN, hydrocyanic acid, may be called formonitrile because it can be hydrolyzed to formic acid. As regards acid power it is extremely weak; its dissociation constant is less than one ten-thousandth of that of acetic acid. It is very poisonous, but is used in 2% solution as a remedy. This reaction also shows that the carbon atom of CN is linked directly to the carbon chain. There are cyanides, however, in which it is the nitrogen atom of the CN group that is linked to the carbon chain. These are isocyanides or isonitriles. CH 3 NEEEC is methyl ixocyanide. Some chemists think that hydrocyanic acid may be a mixture of HCN and HNC, and that the metallic cyanides are mainly isocyanides. Chloroform when heated with alkali and a primary NITROGEN DERIVATIVES 257 amine gives rise to the disagreeable vapor of iso- cyanide : CHC1 3 +R NH 2 =R NC +3HC1. When an isocyanide is hydrolyzed, an amide and formic acid are formed: CH 3 NC +2H 2 O - CH 3 NH 2 +HCOOH. EXPERIMENT. Isocyanide reaction. Mix to- gether in a test-tube a few drops of chloroform, 1 c.c. of aniline, and 2 c.c. of alcoholic KOH. Warm gently. Note the peculiar disagreeable odor of the isocyanide. As soon as this odor is detected, dilute the mixture with much water in the sink, since the fumes are poisonous. Other Cyan-compounds. Cyanic acid may be HO C=N or HN=C=0, or a mixture of both. Sulphocyanic (thiocyanic) acid has sulphur re- placing O in the cyanic acid molecule. Cyan-acids, e.g., cyan-acetic acid, CH 2 CN-COOH, are analogous to monochloracetic acid. Such an acid is much stronger than the simple acid and even stronger than the corresponding monochlor acid. Substituted Ammonias. These may be considered as ammonia in which one or more hydrogen atoms are replaced by organic groups. Primary substituted /H ammonias, N^-H, contain the group NH 2 , called X R 258 ORGANIC CHEMISTRY the amido or amino group. Secondary substituted /H ammonias, N-R, contain the imido group, NH. X R / R Tertiary substituted ammonias, N^-R, have all the X R hydrogen of ammonia displaced. These are all called amines. They are pre- pared by the action of ammonia on alkyl halides: C 2 H 5 Br +NH 3 = C 2 H 5 NH 2 HBr, (Ethylamine hydrobromide) C 2 H 5 NH 2 +C 2 H 5 Br = (C 2 H 5 ) 2 NH HBr, (Diethylamine hydrobromide) (C 2 H 5 ) 2 NH +C 2 H 5 Br = (C 2 H 5 ) 3 N HBr. (Triethylamine hydrobromide) The HBr is removed by treating the above com- pounds with KOH. Amines form salts with acids by adding on the entire acid molecule, N changing its valence from three to five. The salts of alkaloids are of similar nature. Some amines have two NH 2 groups, as ethylene diamine, NH 2 CH 2 - CH 2 NH 2 . The amines may also be prepared by treating an acid amide with sodium hypobromite (see exp.): CH 3 CONH 2 +Br 2 +4NaOH = CH 3 NH 2 +2NaBr (Acetamide) (Methylamine) +Na 2 CO 3 -t-2H 2 O. (Br forms hypobromite with NaOH.) NITROGEN DERIVATIVES 259 EXPERIMENT. Treat 12.5 gm. of dry acetamide in a half -liter flask with 11.5 c.c. of bromine; add a cooled solution of 20 gm. of KOH in 175 c.c. of water until the mixture turns a bright yellow, mean- while keeping the flask cooled with running water. Run this hypobromite mixture by means of a drop- ping funnel rapidly into a solution of 40 gm. of KOH in 75 c.c. of water. Keep the temperature of the liquid at 70-75. Cool the flask if the temper- ature gets above 75. Keep at 75 for thirty min- utes. Add some powdered pumice and distill on a sand-bath. Attach an adapter (see Fig. 19, p. 126) to the condenser; dip this slightly below the surface of strong hydrochloric acid in the receiving flask (50 c.c. C.P. HC1+50 c.c. of water). Distill until the distillate, tested by detaching the adapter momentarily, is no longer strongly alkaline to litmus. Evaporate the acidulated distillate in an evaporating dish heated over wire gauze. When down to small bulk complete the drying in an oven at 110. Pulverize the residue; treat with several portions of 10 c.c. of hot alcohol, filtering the de- canted alcohol into a dry beaker. Crystals of methylamine hydrochloride separate out by cool- info. Filter off the crystals; press between filter- paper; keep part as a specimen. Put the rest into a small test-tube, and add strong KOH solution; methylamine is evolved. Note the odor and the reaction of the gas to litmus. Test its inflam- mability by corking the test-tube with a cork fitted with a glass tube that has a finely drawn tip, and applying a flame to this tip. Heat the 260 ORGANIC CHEMISTRY mixture if necessary to secure free evolution of gas. Nascent hydrogen converts an alkyl cyanide into an amine, CH 3 CN +4H = CH 3 CH 2 NH 2 . (Methyl cyanide) (Ethylamine) Many amines, particularly the primary ammonia bases, are decomposed by nitrous acid. This is a reaction of considerable importance. An ammo- nium nitrite derivative is formed first, but this is so unstable that it breaks down, liberating nitrogen : NH 2 C 2 H 5 +HN0 2 = NH 3 (C 2 H 6 ) N0 2 , (Ethylamine) (Ethyl ammonium nitrite) NH 3 (C 2 H 5 ) NO 2 =N 2 +H 2 +C 2 H 5 OH. Many amines result from decomposition of protein material. Amines resemble ammonia in odor, and their vapors are alkaline to litmus. When dissolved in water they form bases, i.e., they give rise to hydroxyl ions. Many of the amines are more strongly basic than ammonium hydroxide. There are quaternary bases in which four organic groups are linked to nitrogen; these are really sub- stituted ammonium compounds. Tetraethyl ammo- nium hydroxide is (C 2 H 5 ) 4 NOH (cf. NH 4 OH). This is a very strong base; its saponifying power is almost equal to that of sodium hydroxide. If the saponifying power (affinity constant) of LiOH be taken as 100, NITROGEN DERIVATIVES 261 KOHandNaOH=98 (C 2 H 5 ) 4 NOH=79 NH 4 OH= 2 Methylamine, dimethylamine, and trimethyla- mine are gases. They are contained in herring- brine. They are also obtained by destructive dis- tillation of the residue that is left after preparing alcohol from the molasses of beet sugar. HC1 is used to hold the amines as salts. This amine dis- tillate is used commercially to produce methyl chloride, because the latter can be obtained from trimethylamine by treatment with hydrochloric acid: (CH 3 ) 3 N HC1+3HC1 =3CH 3 C1+NH4C1. Choline is a substituted ammonium hydroxide, trimethylhydroxyethyl ammonium hydroxide : It will be noticed that it is also related to primary alcohols. It is of physiological importance. Choline is oxidized to betaine by removal of the H atoms of both the alcohol and the basic hydroxyl groups, (CH 3 ) / N\ CH 2 -CO 262 ORGANIC CHEMISTRY Analogous to choline and betaine is carnitine (novaine), /CH 2 .CH 2 -CH(OH).CO (CN 3 ) 3 N< \ The lecithins are salts of choline. The chief one (distearyl lecithin) contains stearic and glycerophos- phoric acids in combination with choline, having the formula: CH2 OOCisH 3 5 (Stearic acid) CH OOCi 8 H 35 /OH )H 2 O PCX O C 2 H 4 N(CH 3 ) 3 OH (Glycerol) (Phosphoric acid) (Choline) Lecithin is an important constituent of yolk of egg, of nerve-tissue, of bile, and of the envelope of red blood-corpuscles. Phosphatides. The lecithins belong to this class of compounds. Phosphatides contain phosphoric acid in ester combination with an alcohol, generally glycerol, and one or more fatty acid radicles, and also one or more radicles containing nitrogen, generally choline. They are of importance in biochemistry. One of these is cephalin, which has been obtained from brain tissue. It* contains the radicle of stearic acid and of an unsaturated acid of the linoleic acid series, Ci7H 3 oCOOH, while the nitrogenous part differs from choline in having one methyl group instead of three. Muscarine is closely related to choline. It has NITROGEN DERIVATIVES 263 been suggested that it is the aldehyde corresponding to choline considered as an alcohol: CH 2 CHO(+H 2 O) Some chemists believe that the CHO group is combined with water, so that it is really CH(OH)2 as in chloral hydrate. Muscarine is a basic substance classed as an alka- loid (see p. 425). It is very poisonous and is con- tained in toadstools (Agaricus muscarius) and some other plants. Many ptomaines 1 are amine bases. Methyla- mine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, butyl- amine, amylamine, muscarine, and xjholine occur as ptomaines. Cadaverine and putrescine are diamine ptomaines. Cadaverine is /CH2 CH 2 -NH 2 H2 \CH 2 CH 2 -NH 2 ' Putrescine has the formula, CH 2 CH 2 NH 2 CH 2 CH 2 NH 2 1 Ptomaines are organic bases formed by the action of bac- teria on nitrogenous matter. Decomposing animal tissue is very apt to contain ptomaines. Many of them are highly toxic and are the cause of death in certain cases of poisoning by canned meats, etc. 264 ORGANIC CHEMISTRY Neurine, like choline, is a ptomaine-containing oxygen, H=CH 2 Urotropine is hexamethylentetramine, and is obtained by the action of ammonia on for- maldehyde. Acid solutions, even those of very low H ion concentration, act on urotropine, liberating for- maldehyde. Piperazine (spermine) is diethylendiamine, Piperazine acts as a solvent for uric acid, pro- vided the former is present in sufficient concentra- tion. Sidonal, lycetol, and lysidin are piperazine derivatives and are used for the same purpose. Analogous to the substituted ammonias are the substitu- tion derivatives of phosphine (PH 8 ) and arsine (AsH 3 ) Since they will be mentioned in no other place, it may be well in this connection to state that there are organic acids contain- ing phosphorus or arsenic, as, for example, cacodylic acid, which is dimethylarsenic acid, CH 3 CH 3 . OH Nitro Compounds. Nitroparaffins have N of the nitro group linked directly to C of the chain, e.g., nitroethane, CH 3 -CH 2 NO 2 . The nitro com- pounds of the benzenes are much more important NITROGEN DERIVATIVES 265 than are those of the paraffins, and will be considered later. The Nitrites. Ethyl Nitrite, C 2 H 5 NO, and amyl nitrite, CsHn NO, are of importance. Both are used as medicines. Amyl nitrite is a very valuable remedy; its physiological action is similar to that of nitroglycerol (see p. 202), but comes on quickly and is very evanescent. It consists chiefly of isoamyl nitrite. These organic nitrites are often called nitrous esters, being formed by the action of nitrous acid on alcohols. EXPERIMENT. Prepare amyl nitrite as follows: Mix in a small flask 20 c.c. of fermentation amyl alcohol and 15 gm. of finely powdered sodium nitrite. Set the flask in ice- water; add to the alcohol, drop by drop, 5 c.c. of C.P. H2SO4 from a dropping funnel. Amyl nitrite forms a top layer; decant it off into a separating funnel. Add some water to the mixture in the flask and shake; when more amyl nitrite separates out, decant again. Separate the nitrite from the aqueous liquid. Dry with calcium chloride and distill. Note the color, odor, and the effect of cautious inhalation (flushing of the face and vascular throbbing), CHAPTER XIX AMINO ACIDS AND ACID AMIDES AMINO ACIDS Amino or amido acids are acids containing an NH 2 or amido group. Corresponding to mono- chloracetic acid, CH 2 C1-COOH, is aminoacetic acid, CH 2 NH 2 -COOH. The simplest amino acid is aminoformic acid, NH 2 -COOH, called carbamic acid. The free acid is unknown. The salts are unstable, showing a decided tendency to become converted into car- bonates. Ammonium carbamate is of considerable importance in physiology, because it is believed to be one of the forerunners of urea. It can be changed into urea by heating it in a sealed tube at a temper- ature of 135-140: NH 2 - COONH 4 = NH 2 CO - NH 2 +H 2 O. (Ammonium carbamate) (Urea) EXPERIMENT. Prepare ammonium carbamate by bubbling dry C0 2 X and dry NHs simultaneously into alcohol contained in a cylinder or graduate. Secure the dry NHs as previously described (see p. 153). Dry the CO 2 by bubbling it through H 2 S0 4 . When 1 C0 2 is obtained by putting marble chips into a bottle or generator and adding HC1 by a dropping funnel. 266 AMINO ACIDS AND ACID AMIDES 267 a considerable quantity of crystals has been pro- duced, stop the process. Filter off the alcohol; press the crystals between filter-paper. To test the carbamate, dissolve some of the crystals in 5 c.c. of distilled water that has been cooled to 0; and immediately add some cold CaCl 2 solution. No reaction is apparent because calcium carbamate in solution is stable at very low temperatures. Now warm the solution; the carbamate decom- poses and a heavy precipitate of calcium carbonate appears. Leave the rest of the crystals exposed to the air several days; a small amount of a white powder (NH 4 HC0 3 ) is obtained: Ethyl carbamate, or urethane, NH 2 -COOC 2 H5, is an ester having a hypnotic action. Amino acids may be obtained by treating a halo- gen fatty acid with ammonia, thus: H 2 N|H +C1!H 2 C COOH = NH 2 - CH 2 COOH +HC1. (Monochloracetic acid) (Aminoacetic acid) Ammonium salts are, of course, formed. They can also be obtained by decomposing proteins by means of acids, alkalies, or hydrolytic ferments. All the amino-acids that are considered in this chapter are of great importance in physiology. They are very weak acids. In fact they are am- photeric electrolytes, their solutions behaving as if they contained both hydrogen and hydroxyl ions. 268 ORGANIC CHEMISTRY The arnino group gives the basic character to the molecule. Proteins and some other organic com- pounds act in the same manner. Glycocoll (glycin) is aminoacetic acid, /NH 2 CH 2 ^- COOH. It can be produced from glue (or gelatin) by boil- ing with dilute sulphuric acid or baryta water. It can be prepared by allowing an excess- ^of strong ammonium hydroxide to act on monochloracetic acid for twenty-four hours. In the animal body it combines with benzoic acid to form hippuric acid (see p. 360), and with cholic acid to form one of the bile acids, glycocholic acid. % '* /NH-CH 3 Methyl glycocoll, CH 2 < ? , is^alled sar- \COOH cosin. It can be synthesized from monobromacetic acid and methylamine: CH 2 Br - COOH +2CH 3 NH 2 = CHCH CHa-r-CH COOH. (Isobutyl) (Aminoacetic acid) This may occur in the urine in certain diseases. It is a decomposition product of protein, being an im- portant end product of tryptic digestion. C 2 H 5 \ /NH 2 Isoleucin, /CH CH o=c< X OH X NH 2 The relationship of urea to carbamic acid is shown by its preparation from ammonium carbamate by heat- ing in a sealed tube at a temperature of 135: X NH 2 /NH 2 O=C< =0=C< +H 2 0. X ONH 4 X NH 2 (Ammouium carbamate) (Urea) H2 \ 278 ORGANIC CHEMISTRY Its relationship to carbonic acid is evidenced by its production from carbonyl chloride and ammonia: /Cl /NH 2 0=C< +2NH 3 =0=C< +2HC1, X C1 X NH 2 (Carbonyl chloride) also from ethyl carbonate and ammonia: /OC 2 H 5 /NH 2 O=C< +2NH 3 = 0=(\ +2C 2 H 5 OH. X OC 2 H 5 X NH 2 (Ethyl carbonate) That it bears a relationship to cyanic acid, HCNO, and its amide cyanamide, N=C NH 2 , is proved by its preparation from both of these. By hydrolysis cyanamide is converted into urea: CN-NH 2 +H 2 0=0=C/ 2 . \JNJbi2 Mere evaporation of a solution of ammonium iso- cyanate is sufficient to convert the salt into urea (see exp.) ; this involves intramolecular change: X T NH 4 /NH 2 \NH 2 (Ammonium iso-cyanate) The change of cyanate to urea is a reversible reaction. A decinormal solution of ammonium isocyanate changes on standing until it reaches an equilibrium point, at which 95% of the cyanate has become urea. On the other hand a urea solution changes until it reaches the same equilibrium point, i.e., when 5% has been changed to cyanate. AMINO ACIDS AND ACID AMIDES 279 Physiologists have advocated three main hypotheses as to the origin of urea in the animal body, corresponding to the above methods of synthesis, namely, that it is derived from (1) ammonium carbonate, (2) from ammonium carbamate, or (3) from ammonium cyanate. It seems most likely that the derivation of urea is as follows : Ammonia enters the blood of the portal venous system mainly as the result of fermentative and bacterial hydrolysis of the proteins of the food. In the pres- ence of the large amount of carbonic acid in the blood, am- monium carbonate and carbamate are formed in accordance with the laws of mass action; both of these are then converted in the liver into urea by a process of anhydrolysis: ONH 4 /NH 2 /NH 2 - 0=C< ( - H 2 0) -> 0= C ( - H 2 0) \ONH 4 \ONH 4 X NH 2 (Ammonium carbonate) (Ammonium carbamate) (Urea) A certain portion of the amino acids which are not used by the tissues for synthesis of proteins probably become a source of urea in the following manner: The monoamino-acids may be acted on by ferments (deamidization) so that ammonia is split off (the presence of ferments possessing that power has been demonstrated in many organs), and then the ammonia becomes ammonium carbonate and carbamate, and is changed to urea. Arginin may be hydrolyzed by a ferment, arginase, which is present in many organs, urea being one of the products (see p. 270). Urine contains a large quantity of urea, 20 to 30 gm. of urea being excreted in the urine of man in twenty-four hours on a mixed diet. It crystallizes in colorless needles or rhombic prisms. It melts at 132 (corrected melting-point is 132.6). It is very soluble in water and hot alcohol, less soluble in cold alcohol. Bacterial fermentation of urine converts urea into 280 ORGANIC CHEMISTRY ammonium carbonate, hence the ammoniacal odor of decomposed urine. An enzyme urease, also boil- ing with alkalies or acids or superheating with water, can accomplish a similar hydrolysis: / 2 ( 2 NH 4 \ C0< + = >C0 3 . X Of course by the action of alkali NH 3 is liberated from the (NH 4 ) 2 CO 3 , while by the action of acid CO 2 is liberated. This reaction is the basis of Bunsen's and Folin's methods of quantitative estimation of urea. The most satisfactory method of estimation is that in which urease is used. Sodium hypochlorite and hypobromite decompose urea, liberating nitrogen; CO(NH 2 ) 2 +3NaBrO = N 2 +3NaBr +C0 2 +2H 2 0. This reaction is made use of in the usual clinical method for urea estimation. Nitrous acid also liberates free nitrogen (see p. 260) : CO(NH 2 ) 2 +2HN0 2 =2N 2 +CO 2 +3H 2 0. When heated strongly, urea yields, among other substances, biuret, NH 2 -CO-NH-CO-NH 2 , which gives a reddish-violet color reaction with caustic soda or potash containing a trace of copper sulphate (biuret reaction). This reaction is given by oxam- ide, in fact by all substances containing two groups of CO-NH 2 linked together either directly (as in oxamide) or through a single nitrogen (as in biuret) AMWO ACIDS AND ACID AMIDES 281 / /CONH 2 \ or carbon atomf as in CTb, \ ) or through one \ \COJN xi2/ / CO-CONH 2 \ or more CO-NH groups I as in I ). \ NH-CONH 2 / CH2-NH2 may take the place of one of the CONEb groups, as in glycinamide (p. 275). All proteins give the biuret reaction (p. 296) . Urea acts as a weak monacid base toward certain acids, the nitrate and oxalate being particularly characteristic salts. In the common method for extraction of urea from urine, it is precipitated from the urine (previously concentrated by evaporation) by treatment with nitric acid. The urea is liberated from the nitrate by treating the latter with barium carbonate, EXPERIMENT. (1) Synthesize urea as follows: Heat 25 gm. of powdered potassium cyanide in an iron dish until it begins to fuse (do this under a hood), then add gradually 70 gm. of red oxide of lead a little at a time, stirring in well. When the frothing ceases pour on an iron plate. When it is cool powder the mass, separating out the metallic lead. Digest this crude cyanate for an hour with 100 c.c. of cool water. Filter through a plaited fil- ter into an evaporating dish. Add to the filtrate 25 gm. of ammonium sulphate that has been dissolved in a small quantity of water. Evaporate to dryness on a water-bath, stirring frequently to prevent crust- ing over. Cool the residue and powder it in a mor- tar. Transfer it to a small flask, add 100 c.c. of 282 ORGANIC CHEMISTRY alcohol, attach to a reflux condenser, and boil for fifteen minutes. Filter off the hot alcohol into an evaporating dish. Use 25 c.c. more of alcohol in a similar manner. Evaporate the alcohol on a water-bath to very small bulk. When it is cool, urea crystals should form. Test a few crystals or some of the solution as below. (2) Urea tests, (a) Put one drop of concentrated urea solution on a glass slide; mix with it one drop of colorless concentrated nitric acid. Place a cover- glass over the crystals and examine under a micro- scope. (6) In a test-tube melt some dry urea, then heat gently for a minute while gas (NHa) is being evolved. Cool; add 1 c.c. of water, then an equal amount of 20% NaOH solution, and finally a small drop of very dilute copper sulphate solution. A violet or pinkish color is obtained. This is called the biuret reaction (see above) : NH 2 NH 2 oc/ + \co= X X (Urea) ...... "(Urea) =NH 2 CO NH CO-NH 2 +NH 3 . (Biuret) If the heating has been continued beyond a cer- tain point, an insoluble compound, cyanuric acid, (HCNO)3, is formed; this results from the combina- tion of one molecule of biuret with one of urea, 2NHs being eliminated. Veronal is a urea derivative, being diethylmalonyl- urea or diethylbarbituric acid, AMINO ACIDS AND ACID AMIDES 283 C 2 H 5 CO V >CO. This is used as a hypnotic. The sodium salt of veronal is also used for the same purpose. Another hypnotic related to urea is hedonal, which is really a carbamate similar to urethane. Hedonal is methylpropylcarbinolurethane : /NH 2 C0< /CH 3 ^0CR<( ^C 3 R 7 Bromural is another hypnotic, derived from urea. It is monobrom-iso-valeryl-urea, CH 3 - CH - CHBr CO NH - CO - NH 2 . CH 3 Neuronal is a hypnotic, having a somewhat similar structure, CBr(C 2 H 5 ) 2 CONH 2 . CHAPTER XX ACID IMIDES. COMPLEX AMINO AND IMIDO COM- POUNDS, INCLUDING POLYPEPTIDES ACID IMIDES THESE contain the group NH, illustrated by CH 2 C(X succinimide, | >NH. They are formed CH 2 CCr from acid amides by loss of ammonia, the amide of a dibasic acid being necessary: \ CH 2 -CONH 2 CH 2 -CO I = | >NH+NH 3 . CH 2 -CONH 2 CH 2 -CO X (Succinamide) (Succinimide) OTHER AMINO AND IMIDO COMPOUNDS /NH 2 Guanidin, NH=C^ , may be considered as an \NH 2 imido derivative of urea, and might be called imido- carbamide. It can be synthesized from cyanamide and ammonia: /NH 2 CN-NH 2 +NH 3 =NH=C< T . (Cyanamide) \NH 2 (Guanidin) It is more strongly basic than urea, undoubtedly because of the changing of the carbonyl linking of 284 AMINO AND IMIDO COMPOUNDS 285 urea for the naturally basic NH group. Methyl- /NH 2 guanidin, HN=CC=0. H.W This is the skeleton of the uric acid formula. The presence of two urea molecules and of a carbon chain is shown by the nature of the decomposition prod- ucts of uric acid resulting from oxidation and hydrol- ysis: AMINO AND IMIDO COMPOUNDS 287 NH CO I. CO C NH V || >CO+H 2 0+0 [ C NH X NH- (Uric acid) [treated with cold HNO 3 ] NH CO I I NH 2\ II. = CO CO + >CO. | | NH/ NH CO (Alloxan) (Urea) NH C CO ( NH C (Alloxan) [trea warm t ^0 X>+0 = :o ted with [NOs] NH CO CO +CO 2 . NH CO (Parabanic acid) NH ( 1 :o NH ( 1 ^O CO 1 +H 2 = CO 1 NH ( banic acid) [tr :o 3ated with alkali] NH 2 ( (Oxah ^OOH. iric acid) III. NH CO IV. CO +H 2 = NH 2 COOH (Oxaluric acid) [boiled with water] NH 2 COOH +| NH 2 COOH. (Urea) (Oxalic acid) N C The presence of the pyrimidin ring, C C, in uric N C acid is shown by Traube's synthesis, which is as fol- lows: Cyanacetic acid and urea are treated with 288 ORGANIC CHEMISTRY POC1 3 ; the latter removes hydroxyl from the acid, and urea takes its place to form cyanacetyl urea: /CN (1) CH 2 .COOH+NH 2 -CO-NH 2 = (Cyanacetic acid) (Urea) CH 2 CN +H 2 0. NH C NH 2 II O (Cyanacetyl urea) Treating cyanacetyl urea with alkali causes a shifting within the molecule, resulting in the formation of monoamino-dioxy-pyrimidin, HN C=O (2) 0=C CH 2 . HN C=NH This is treated with HNO 2 , giving HN C=O (3) o=C C=NOH. I I HN C NH By reduction this becomes HN C O 0=C C NH 2 , I II HN C NH 2 . AMINO AND IMIDO COMPOUNDS 289 which when acted on by CC100C 2 H 5 +KOH gives (Ethyl chlorcarbonate) HN C=O (4) o=C C NK COOC 2 H 5 , HN C NH 2 a pyrimidin derivative of urethane. By heating this potassium salt (dry) to 150, then later to 180- 190, alcohol is split off, leaving uric acid (as potas- sium urate) : HN CO (5) o C C NK X | || >C=0+C 2 H 5 OH. HN C NIT This synthesis conclusively proves the structure of uric acid. Another interesting synthesis, because it is anal- ogous to one which may occur in the animal body, (at least in birds), is effected by heating together urea and trichlorlactamide : H) NH CO (NH 2 ) CO C (HOH) NH V (H) \ I >co (H) NH C (C1 3 ) NH^(H) (Urea) (Trichlorlactamide) (Urea) The groups in parenthesis do not enter into the uric acid molecule, but unite to form NH 4 C1, HC1, and H 2 0. 290 ORGANIC CHEMISTRY /NH COv Dialuric acid, COC >CHOH, appears in \N H O O' the case of birds to be an intermediate body in the synthesis of uric acid by the liver. It is formed by the combination of urea with tartronic acid (p. 221). By the addition of another urea molecule to this, uric acid is produced: (HOH)+NH^(H) V NH C(O) (Dialuric acid) (Urea) NH CO = CO C NH X >CO + 2H 2 0. NH C NIT (Uric acid) Analogous synthesis in the case of mammals has not been proved. Uric acid has been synthesized by heating together glycocoll and urea. On the other hand, uric acid when heated in a sealed tube with HC1 yields glycocoll. Tautomerism of uric acid. Uric acid exists not only in the form corresponding to the above formula (the lactam state) but also in another form (the lactim state), in which the three atoms are in hydroxyls: N=C OH i I HO C C NH AMINO AND IMIDO COMPOUNDS 291 The lactam form is less stable. It is stated that in the urine uric acid is in the lactim form. Uric acid acts as a weak dibasic acid, forming urates. It does not, however, play any part in the acid reaction of urine. It is believed to exist mainly in the form of monosodium urate in both the blood and the urine. In very acid urine there is some free uric acid. It often crystallizes out as a reddish deposit from strongly acid urine. About 0.7 gm. is excreted daily by man. Pure uric acid is a color- less crystalline powder. It is almost insoluble in cold water and alcohol. Uric acid reduces Fehling's solu- tion, but does not reduce an alkaline bismuth solution. EXPERIMENT. (1) Add 5 c.c. of 20% HNO 3 to a little uric acid in an evaporating-dish ; evaporate to dry ness on a water-bath. Alloxantin is formed. To the residue add baryta water; a blue color appears. (2) Repeat the above, but instead of using baryta expose the residue to fumes of ammonia. A red color is obtained, due to murexide. This test is called the murexide test. If much ammonia is present in the air, the residue will be reddish because of the ammonia taken up. Ammonia converts alloxantin into purpuric acid, HN CO NH OC NH OC C/ \C CO. II II HN CO OC NH Murexide is the ammonium salt of this acid. 292 ORGANIC CHEMISTRY /NH CH NIL Allantoin, CO >CO, results from \NH-CO NH 2 X careful oxidation of uric acid by potassium per- manganate. It occurs in the urine of calves and dogs, and at times in human urine. Purin bodies. Uric acid and all the purin bodies contain the double-ring nucleus N C C C N v i i \r* /O. N C W The main ring is the pyrimidin ring; the purin nucleus, therefore, is pyrimidin with urea attached as a secondary ring. 1 The relationship of the purin bodies is shown below: Purin itself has an H atom at each of the positions numbered 2, 6, 7, and 8. It can be prepared from uric acid. (1) N C (6) NH CO II II (2) C C (5) N(7)v CH C NH V >C(8) || || >CH (3) N C (4) N(9) (Purin nucleus) (Hypoxanthin) (6-oxypurin) 1 The purins and pyrimidins are heterocyclic. We prefer to discuss the chemistry of them at this point because of their relationship to urea and proteins. They show no similarity to the typical heterocyclic compounds. AM I NO AND I MI DO COMPOUNDS 293 NH CO NH CO CO C NIL CO C N(CH 3 ) I II >CH \ OH NH-C W ./ CH (CHs)N C N (Xanthin (Theobromine, dimethylxanthin) (2, 6-dioxypurin) (3, 7-dimethyl-2, 6-dioxypurin) (CH 3 )N CO I I /(CH 8 ) CO C W H I (J IT (CHs)N- (Caffeine, theine, trimethylxanthin) (1, 3, 7-trimethyl-2, 6-dioxypurin) NH CO CO C NIL I II >co NH C NH X (Uric acid) (2, 6, 8-trioxypurin) CH C NH H 2 N C C NH N=C NH 2 NH CO >AJ.2J-1 V> O Ix J-J-v CH || || >CH IN v IN - N C W (Adenin) (Guanin) (6-aminopurin) (2-amino-6-oxypurin) There are a number of methyl purins besides caffeine and theobromine, as, 1 methyl xanthin, 7 methyl xanthin (heteroxanthin) , 1, 7 dimethyl xanthin (paraxanthin), and 7 methyl guanin. The purins are also called alloxuric, xanthin, or nuclein bodies. Caffeine and theobromine when taken as food are excreted in the urine partly unchanged and partly 294 ORGANIC CHEMISTRY as monomethyl and dimethyl xanthins. Only 35- 40% of caffeine and theobromine appear in the urine as purine bodies. A number of investigators agree in the assertion that tea and coffee do not increase uric acid excretion. The other purins are excreted mainly as uric acid. It is believed by some that on a diet that is free of purin bodies, the amount of purins excreted daily is a fixed quantity for each individual (cf. creatinin). In the case of mammals the purin bodies have their origin in the nucleic acids of nucleoproteins, both those of the tissues and those of the food. Some of the purins, mainly xanthin and hypo- xanthin, are found in muscle, and therefore in meat extract. Beef tea or a solution o meat extract contains as its organic constituents chiefly creatin, purin bodies, and sarcolactic acid. Theobromine (dimethylxanthin) is found in choc- olate and cocoa. It is called an alkaloid (see p. 425). Caffeine or theine (trimethylxanthin) is the alka- loidal principle in tea and coffee Both theobromine and caffeine are used as medicines. EXPERIMENT. Try the murexide test (see p. 291) on a little caffeine. Repeat, substituting bromine water for HNOs. Pyrimidin derivatives. These are derived from nucleic acid by hydrolysis whether by the action of acids or by post-mortem autolysis of animal tissue. The most important are uracil, thyrnin and cytosin. AMINO AND IMIDO COMPOUNDS 295 Uracil is 2, 6 dioxypyrimidin, NH C= I I O=C CH. Thymin is 5 methyl 2, 6 dioxypyrimidin, NH C=0 O=C C CH 3 . I II NH CH Cytosin is 6 amino 2 oxypyrimidin, N=C NH 2 C CH NH CH As an illustration of a nucleic acid might be men- tioned one which has been obtained from a nucleo- protein of the thymus gland. It is believed to consist of the linking together of four hexose (p. 231) and four phosphoric acid molecules with one mole- cule each of guanin, adenin, thymin and cytosin. To it has been assigned the formula : Leucomaine is a term applied to basic substances found in living animal tissues. The purin bodies and the creatinin group of compounds are the chief leucomaines. 296 ORGANIC CHEMISTRY DIPEPTIDES AND POLYPEPTIDES Because of the fact that the decomposition prod- ucts of proteins include amino-acids (as alanin, glycocoll, leucin, tyrosin, aspartic acid, etc.) and the hexone bases, it has been proposed to explain the structure of the protein molecule as a chaining to- gether of these amino bodies by means of the removal of OH of a carboxyl group of the one amino body and an H of the amino group of another (cf. formation of acid amides), thus: /!OH HI NH 2 CH 2 - CO"- -NH CH 2 COOH; ; (Glycylglycin) or a more complicated chain, as: -NH CH CO-NH CH - CO-NH CH CO-hNH C-iHg CH 2 ' [ 2 -COOH C 3 H 6 -CH 2 -NH 2 (Leucin) (Aspartic acid) (Lysin) Of course the above is supposed to be only a part of the formula. This theory of the constitution of protein mole- cules gives the best explanation of the universality of the biuret test as applied to proteins (see p. 281) the test being due to the many CONH groups. On the basis of this hypothesis the problem of the synthesis of protein is now being vigorously attacked. Compounds have been synthesized in which two, three, and even up to eighteen molecules have been made to combine in this manner; these synthetic bodies are called pep tides. AMINO AND IMIDO COMPOUNDS 297 If two molecules have united, the compound is a dipeptide; for example, glycylglycin, NH 2 - CH 2 CO NH - CH 2 COOH. Polypeptides are built up from more than two mole- cules; they include tripep tides (as diglycylglycin, NH 2 CH 2 CO NH CH 2 CO NH CH 2 COOH), tetrapeptides, pentapeptides, hexapep tides, etc. A polypeptide composed of three leucin and fifteen glycocoll molecules has been synthesized, the formula being CdsHgoOigNis and the molecular weight 1213. Certain polypeptides, identical with those pro- duced synthetically, have been obtained by partial hydrolysis of proteins. The more complex poly- peptides show certain resemblances to peptones in their actions. They taste bitter. They are pre- cipitated by the same reagents, and give the biuret test. Those that are composed of amino acids of the same optical activity as those occurring in proteins are hydrolyzed by trypsin. Their solutions are colloidal. E. Fischer, who is doing such brilliant work in this line of synthesis, is inclined to doubt whether this comparatively simple method of linking is the only kind of linking existing in protein molecules. PROTEINS Proteins are complex nitrogenous compounds that yield on complete hydrolysis mainly amino acids, hexone bases (p. 270), and ammonia. They vary 298 ORGANIC CHEMISTRY widely in the proportion of the different amino acids and bases contained in their molecules; e.g., haemo- globin has not less than 20% of leucin, but gelatin only about 2%; on the other hand there is 16.5 per cent of glycocoll in gelatin and none in haemoglobin. Gelatin has very little of aromatic amino acids. Tryptophan seems to be the amino acid of proteins which is most essential to proper nourishment. Most proteins contain S (cystin), some P. Since they form colloidal solutions, molecular weight determination has not been successful. The lowest possible molecular weight of haemoglobin is over 16,000, calculating on the basis of the percentage composition, and supposing that there is one atom of iron in the molecule; this corresponds to the formula : The most important classes of proteins are pro- tamines, histones, albumins, globulins, phospho- proteins, scleroproteins, compound proteins (chro- moproteins, glucoproteins and nucleoproteins), derived proteins (coagulated proteins, acid and alkali metaproteins, proteoses and peptones), and certain classes of vegetable proteins called glutelins and prolamines (or gliadins). lodothyrin (thyroiodin) is the iodin-containing portion of the compound protein, thyreoglobulin, present in thyroid tissue. Oxyproteic acid, C43H 8 2Ni4O 3 iS, is a derivative of protein. It is found in the urine, and may be greatly increased in some pathological conditions. CHAPTER XXI UNSATURATED HYDROCARBONS AND THEIR DERIVATIVES THE most important unsaturated hydrocarbons are the ethylenes and acetylenes. Their unsaturation consists in having two or three bonds or linkings between one or more pairs of carbon atoms, thus: 0=C, C=C, 0= C 0= C, C=C=C, etc. The unsaturation is undoubtedly not of so simple a nature as is indicated by the double and triple bond. Unsaturated substances of this nature readily form addition compounds, as with iodine and bromine. This fact is taken advantage of in analysis of fats and oils, the estimation of the oleic and other unsaturated acids being made by the use of an iodine solution (see p. 206). Another illustration of the formation of addition compounds is the production of ethylene bromide, C2H 4 +Br2=C 2 H 4 Br2. Halogen acids (HBr, HI) are added to these hydrocarbons in similar manner: C2H 4 +HBr =C2H 5 Br. The addition compound is, of course, saturated. That the place of double linking is a weak point in the chain is shown by the fact that vigorous oxidation results in rupture of the C chain at this point. 299 300 ORGANIC CHEMISTRY ETHYLENES Ethylenes or olefins, C n H 2n , form an homologous series. Ethylene (ethene, olefiant gas), CH2=CH2, is the only member of importance, and is contained in coal gas (about 2%). It is colorless and burns with a yellow flame. Ethylene forms an explosive mixture with oxygen. It is obtained by decom- position of ethyl sulphuric acid by heat, C2H5HSO4 EXPERIMENTS. (1) In a liter flask heat a mixture of 30 c.c. of alcohol and 83 c.c. of C.P. H 2 SO 4 (it is stated that HsPCU can be used instead of H 2 SO4, avoiding the carbonizing), using a sand-bath. Put a little sand in the flask. Use a three-holed cork. It is best to use rubber stoppers for the entire apparatus because of the pressure of gas that is obtained. Insert a dropping funnel, also a ther- mometer placed so that the bulb is immersed in the liquid. Connect with a series of wash-bottles as shown in the diagram; the first bottle having H 2 SO4, the Woulff bottle (having a safety-tube) containing dilute NaOH solution, and each of the last bottles having a mixture of 10 c.c. of bromine and 10 c.c. of water. A loosely corked flask partly filled with dilute alkali catches any bromine vapor that may pass over. Begin heating the flask, and when the temperature reaches 170-175 this is maintained thereafter. At the start raise the safety-tube of the Woulff bottle out of the liquid, and attach a piece UNSATURATED HYDROCARBONS 301 of tubing. By means of this tube bubble the evolved ethylene through a mixture of solutions of potassium permanganate and sodium carbonate in a test-tube (Von Baeyer's reagent l ) until the pink color is lost and a brownish precipitate of hydrated manganese dioxide appears. Lower the safety- tube and then begin running slowly into the flask, through the dropping funnel, a mixture of alcohol FIG, 24. and sulphuric acid (100 c.c. of the former to 85 c.c. of the latter). Keep up a steady production of ethylene until the bromine is almost decolorized. The bromine bottles should stand in ice-water. Disconnect the flask and then remove the flame. 1 Von Baeyer's reagent is decolorized by formic and hydroxy- benzoic acids, by malonic ether, phenols, aldehyde, benzalde- hyde, aldehyde bisulphite, acetone, acetophenone, glycerol, and some sugars (because of oxidation of these substances), as well as by unsaturated compounds. 302 ORGANIC CHEMISTRY Wash the ethylene bromide with water in a separat- ing funnel, and finally shake it with NaOH solution. Draw off the bromide into a flask, add dry calcium chloride, and cork. After a day or so distill, noting the boiling-point (130.3, but 129.5 at 730 mm.). Also take the specific gravity (2.1785 at 20). The bromide is easily solidified, melting at 9.5. (2) Bubble coal gas into Von Baeyer's reagent, as above. Allyl alcohol (propenol), CH 2 =CH CH 2 OH, is an unsaturated alcohol corresponding to the hydro- carbon propene, CH 2 =CH CH 3 . Its radicle, C 3 H 5 , is called allyl. This alcohol can be made from gly- cerol. Acrolein (acrylic aldehyde), CH 2 CH CHO, is the aldehyde from the above alcohol. It is pro- duced from glycerol (see p. 202) : OH OH H H CH 2 CH CH O = CH 2 =CH CHO+2H 2 0. (Glycerol) (Acrolein) EXPERIMENT. In a dry test-tube mix 4 c.c. glycerol and 0.3 c.c. of 85% phosphoric acid. Fit the tube with a stopper and bent delivery tube. Dip the end of this tube in 2 c.c. of water in a small test-tube. Heat the glycerol to a high temperature. Finally test the solution for reducing power and with SchhT s reagent (aldehyde tests). By oxidation it becomes acrylic acid, = CH-COOH. UNSATURATED HYDROCARBONS 303 Crotonic acid is CH 3 -CH CH-COOH. Oleic acid is a member of the acrylic acid series. It has the formula, CH 3 (CH2)7CH=CH(CH 2 ) 7 COOH. It is contained in combination with glycerol as glyceryl trioleate, in many oils, as in olive oil and whale oil, and in animal fats. Oleic acid forms crystals, melting at 14. Hydriodic acid converts it into stearic acid; this is brought about by addition of hydrogen, thus : ; . " CisH340 2 +2H = (Oleic acid) (Stearic acid) This reaction is now taken advantage of commer- cially in the process of hydrogenation of oils, by which they are converted into solid fats. In this process hydrogen gas is used, and a catalyzer (generally nickel) is employed to facilitate reaction with the olein. Fusion with caustic potash results in the formation of palmitic and acetic acids. EXPERIMENTS. (1) Dissolve two drops of oleic acid in a few cubic centimeters of ether in a test- tube; shake with a little Von Baeyer's reagent (see p. 301). (2) Shake some ether with a little bromine water; the ether becomes yellow. Add a few drops of oleic acid and shake. The bromine is taken up, so that the color is lost. Erucic acid, CH 3 (CH 2 ) 7 -CH== CH(CH 2 )nCOOH, is present in some oils, as cod-liver oil. 304 ORGANIC CHEMISTRY Linoleic acid, CirHsi-COOH, is believed now to be an acid somewhat similar to oleic acid, but it has two double linkings instead of one. Its molecule takes up four Br atoms, producing tetrabromstearic acid. Its glyceryl ester is contained in linseed oil. It has the power of taking up oxygen from the air and becoming a hard solid substance, hence its use in paints. Ricinoleic acid, CH 3 (CH 2 ) 5 CH(OH).CH 2 .CH== CH(CH 2 ) 7 COOH, is present in castor oil in combination with glycerol. ACETYLENES These hydrocarbons, C n H 2n _ 2 , form a series of which few members are known. Acetylene, CH^CH, is the only important mem- ber. Small quantities are synthesized directly from carbon and hydrogen when a stream of hydrogen is passed between the carbon poles of an electric arc- light, a small quantity of methane being formed at the same time. It is formed when a Bunsen burner " snaps back." The gas is made most easily and cheaply by the action of water on calcium carbide, C 2 Ca+2H 2 0=C2H2+Ca(OH)2. When used with a special burner, it gives a brilliant light, and is used as an illuminating gas. It is a colorless gas of unpleasant odor. It is very soluble in acetone. UNSATURATED HYDROCARBONS 305 EXPERIMENTS. (1) Put 10 gm. of calcium car- bide in a dry flask or bottle, cork with a two-holed cork. By one hole suspend a dropping funnel containing water, and into the other hole fit a bent delivery tube. Let the water drop on the carbide very slowly. Bubble the acetylene into Von Baeyer's reagent until the test is secured. Then connect with a platinum-tipped glass tube such as is used for burning hydrogen. Light the acetylene; a brilliant flame is obtained. (2) Test the acetylene by inverting a beaker moistened inside with a solution of cuprous chloride in ammonia over the stream of gas; a red precipitate of copper acetylide, C2CU2, is formed. Repeat the experiment, causing a Bunsen burner to strike back, thus producing acetylene. The cuprous chloride is easily prepared as follows : dissolve 0.5 gm. of copper sulphate in a little water, add 2 c.c. of concentrated ammonium hydroxide, then 1.5 gm. hydroxylamine hydrochloride, and dilute to 25 c,c, CHAPTER XXII SULPHUR DERIVATIVES SULPHUR may take the place of oxygen in alco- hols or ethers, forming sulphur alcohols and ethers, as CH 3 -SH (cf. CH 3 OH), CH 3 -S-CH 3 (cf. CH 3 OCH 3 ). Sulphur alcohols are called mercaptans or thioal- cohols. The ethers are dialkyl sulphides. When they are oxidized, as with nitric acid, sulphonic acids are formed, CH 3 -SH+30==CH 3 -S0 3 H. The sul- phonic acid group is S0 3 H. Sulphonic acids may be looked upon as sulphuric acid in which an hydroxyl group is replaced by an organic group: /OH /C 2 H 5 SO 4: C 6 H 5 OH+3HON0 2 =C 6 H 2 (N0 2 ) 3 (OH) +3H 2 0. (2) Warm gently a little picric acid with 5 c.c. of petroleum ether in a test-tube; a colorless solution is AROMATIC HYDROXY COMPOUNDS 343 secured (no ionization). Pour the petroleum ether into water and shake ; the water becomes yellow from the picric acid dissolved in it (ionization). (3) Immerse pieces of woolen, silk, and cotton cloth in picric acid solution for fifteen minutes. Wash them thoroughly with running water. Which are dyed? Aminophenols (seep. 382). Phenolsulphonic acids (see p. 393). Ca!= NCG+CaCOs. . C 6 H 5 |COO_ CeH/ (Benzophenone) b. By distilling salts of two different aromatic acids, such as a salt of benzoic and one of toluic acid : >CO = /. C 6 H 5 COOM C 6 H 5 (Phenyltolylketone) 1 The salt usually employed is that of calcium. M means a metal. AROMATIC HYDROXY COMPOUNDS 355 c. By distilling a salt of an aromatic acid with one of a fatty acid : C 6 H 5 COOM C 6 H 5x + = >CO+M 2 C0 3 . CH 3 COOM CH 3 / (Methyl phenyl ketone or acetophenone) Acetophenone may also be obtained by adding aluminium chloride to a mixture of benzene and acetyl chloride. It is a crystalline substance melting at 20.5, and is slightly soluble in water. It is used in medicine as a hypnotic under the name of hypnone. CHAPTER XXVII AROMATIC ACIDS MONOBASIC ACIDS AROMATIC acids are in general analogous with those of the paraffins, being monobasic, dibasic, etc. The representative monobasic acid is benzoic, CeHs-COOH. This acid^oF\i) great commercial value and of much physiological interest, since, as will be explained later, it is the end product of the oxidation in the animal body of a large number of benzene derivatives having oxidizable side chains. It can. be prepared by numerous reactions, the most important of which are as follows : 1. By oxidation of any benzene derivative with a single fatty side chain. It follows from this that if an aromatic substance yields benzoic acid on oxidation, it must contain only one side chain. When two side chains exist, a dibasic acid (phthalic) is obtained. Thus the hydrocarbons of the benzene series, CeHsCHs, C6H 5 C2H 5 , CeHsCaHT, their monacid alcohols and aldehydes, CoHsCHsOH, CeHsCHsCI^OH, CeHsCHO, etc., and their halogen derivatives where the halogen is situated in the side chain, all yield benzoic acid when oxidized. 2. By hydrolysis of benzonitrile, CeH^CN (see 356 AROMATIC ACIDS 357 p. 256). The reagent can be obtained by substitut- ing the CN group for an H of benzene, either by distilling potassium benzene sulphonate with potas- sium cyanide, C 6 H 5 SO 3 K +KCN = C 6 H 5 CN + K 2 SO 3 , or by heating a diazonium salt with Cu2(CN)2 (see p. 385). 3. By treating benzoyl chloride (see p. 359) with water, C 6 H 5 CO|C1+H|OH. 4. By treating boiling toluene with chlorine, whereby benzotrichloride, CeHsCCls, is produced, which is then boiled with water (see exp. below) : CT~H lOH Cl+H Cl H OiH =C 6 H 5 COOH+3HC1+H 2 0. OH This is the ordinary commercial method. 5. By sublimation or treatment of gum benzoin with alkalies. 6. By heating hippuric acid (see p. 360) with hydrochloric acid (hydrolysis) : CH 2 COOH+H 2 = (Hippuric acid) /NH 2 Benzoic acid forms needle-shaped crystals, which melt at 121.3 (corrected) and readily sublime. It is slightly soluble in cold water, but its solubility increases with rise in temperature until, at 90, 358 ORGANIC CHEMISTRY the water contains 11.2% of the acid, and the crystals that remain undissolved liquefy and form a layer beneath the water. When the temperature is further raised in a closed tube, the two layers gradually mix till, at 116, a homogeneous liquid is obtained. Salicylic acid (p. 363) behaves in a similar manner. The lower liquid layer is a solution of water in the acid, not melted acid. It is soluble in alcohol and ether, and volatilizes with steam. Its salts and derivatives are very numerous, and are analogous with those of acetic acid. Most of them are soluble in water. Of the metallic salts those of sodium and am- monium are employed as medicines. The ethereal salts are prepared in the same way as are those of acetic acid (see exp. (1) (a) ). Balsams (e.g., balsam of Tolu and balsam of Peru) contain as their important constituents benzoic and cinnamic acids, both as free acids and as their esters in combination with benzyl alcohol. Gum benzoin is a balsam containing less cinnamic acid than other balsams. EXPERIMENTS. (1) Preparation of benzoic acid. Put into a flask 5 c.c. of benzotrichloride, 100 c.c. of water, and small pieces of pumice. Attach to a reflux condenser and boil for two hours. Before cooling add 200 c.c. of hot water and filter at once. Cool, collect the crystals on a filter, recrystallize from hot water, and make the ethyl benzoate test on the dried crystals as follows : to some of the dried benzoic acid add 1 c.c. of alcohol and about 3 c.c. AROMATIC ACIDS 359 of concentrated H 2 SO 4 . Heat; just as it begins to boil, notice the peppermint-like odor of ethyl benzoate. Save a sample of benzoic acid. (2) Heat together 1 c.c. of benzaldehyde and an excess of potassium permanganate solution until the odor of benzaldehyde is imperceptible. Add per- manganate as required to maintain a pink color. Decolorize with a few drops of alcohol. Cool, filter, and add HC1 to the filtrate; benzoic acid crystallizes out: C 6 H 5 CHO +0 = C 6 H 5 COOH. (3) Sublime benzoic acid from impure benzoic acid, (see p. 13). BENZOIC ACID DERIVATIVES Benzoyl chloride, the acid chloride of benzoic acid, CeHsCOCl, can be obtained by the action of chlorine on benzaldehyde, or by the action of PCls on ben- zoic acid: C 6 H 5 COOH+PCl5=C6H5COCl-fPOCl3 +HC1. It is more stable than acetyl chloride, not being decomposed by water in the cold. It resembles acetyl chloride, however, in that it reacts with the hydroxyl group of alcohols to form esters of ben- zoic acid. The presence of caustic alkali greatly facilitates this reaction. It reacts thus with the hydroxyl groups in dextrose, the resulting ester being insoluble in water and in dilute alkali. EXPERIMENT. To 10 c.c. of 10% NaOH add 4 drops of glycerol and 1 c.c. of benzoyl chloride. Cork the tube, and shake until a curdy precipitate 360 ORGANIC CHEMISTRY forms, cooling the tube frequently. Add 10 c.c. of water, shake and filter. Crystallize the glyceryl tribenzoate from 15 c.c. of hot 65% alcohol. The substitution products of benzoic acid are numer- ous, for of each there may be an ortho, met a, and para variety. They can be made by oxidizing the corresponding substituted toluenes, or by direct substitution of one or more of the hydrogens of the phenyl radicle in benzoic acid, the methods being the same as are used for the substitution products of benzene. The chlorbenzoic acids, the nitrobenzoic acids, the aminobenzoic acids, and the sulpho- benzoic acids are examples (see p. 394). The aminobenzoic acids are weaker than benzoic acid, while the nitrobenzoic acids are stronger. Novocaine is a derivative of para-aminobenzoic acid, C 6 H 4 (NH 2 )COO CH 2 CH 2 N(C 2 H 5 ) 2 - HCL It is built up from ethane by substitution of an H in each CH 3 group, diethylamine hydrochloride being the second substituting group. It is a local anaesthetic, introduced as a substitute for cocaine. Stovaine and alypin, local anaesthetics of some- what similar nature, are also benzoic acid derivatives. An important compound of benzoic acid, from a biochemical standpoint, is hippuric acid. This is benzoylaminoacetic acid, CeHsCO-NH-CH^COOH. It is present in the urine of herbivorous animals, being produced in the kidney by synthesis from glycin and benzoic acid. It also appears in human urine when benzoic acid is administered, or when AROMATIC ACIDS 361 foods yielding it in the organism are ingested. It may be prepared in the laboratory by several methods: 1. Heating glycocoll and benzoic acid to 160 in a closed tube. 2. Shaking glycin dissolved in sodium hydroxide solution with benzoyl chloride (see exp. below): CeHsCOlCl +H|HNCH 2 COOH = ' = C 6 H 5 CO-NH-CH 2 COOH+HC1. 3. Heating benzamide with chloracetic acid (ben- zamide is analogous to acetamide, see p. 274) : C 6 H 5 CONH;H +C1 CH 2 COOH = = C 6 H 5 CO - NH CH 2 COOH +HC1. Hippuric acid is relatively insoluble in cold water, alcohol, and ether, and forms long rhombic crystals, having a melting-point of 187.5 (corrected). It is readily decomposed by boiling with acids or alkalies, and also decomposes when urine containing it under- goes fermentation. EXPERIMENTS. (1) Synthesize hippuric acid. Shake together 4 c.c. of benzoyl chloride and a solution of 2.5 gm. of glycocoll in 30 c.c. of 10% NaOH (keeping the flask corked) until the odor of the chloride has disappeared. Cool whenever the mixture gets hot. Filter, and acidulate the alkaline filtrate with HC1. Collect the hippuric acid on a filter, wash with a little water, press dry between filter-paper, and recrystallize from hot water. Save a sample. Test part of it as follows. 362 ORGANIC CHEMISTRY (2) (a) Test the solubility of hippuric acid in petroleum ether (compare benzoic acid). (6) Heat a little dry hippuric acid in a test-tube; benzoic acid sublimes, while the residue becomes reddish. Corresponding to toluene there are four mono- basic toluic acids. Three of these (o-, w-, p-) have /CH 3 the formula CoH^ ~~ ,-,-.. and are made- by oxidiz- \COOH ing the corresponding xylenes with nitric acid. The fourth has the formula C 6 H 5 CH 2 COOH, and might properly be called phenyl-acetic acid. It is obtained by treating benzyl chloride, C6H 5 CH 2 C1, with potassium cyanide and hydrolyzing the result- ing nitrile (C 6 H 5 CH 2 CN) : C 6 H 5 CH 2 CN +2H 2 O = C 6 H 5 CH 2 COOH +NH 3 . A homologue of this is phenyl-propionic or hydro- cinnamic acid, C 6 H 5 CH 2 CH 2 COOH. Cinnamic acid is an unsaturated compound, its formula being C 6 H 5 -CH=CH.COOH. It is used therapeutically. Mandelic acid is a hydroxy acid, its formula being C 6 H 5 -CHOH.COOH. Mesitylene yields only one acid, mesitylenic, . This is of importance because it COOH can be converted into metaxylene by distillation with lime (cf. benzene, p. 319): ., = C 6 H 4 +CaC0 3 . \COOH X CH 3 (m) AROMATIC ACIDS 363 PHENOLIC MONOBASIC ACIDS An acid group may exist along with one or more phenolic hydroxyl groups. According to the number of the latter groups we may have mono-, di-, and tri- hydroxybenzoic acids. /OH A. Monohydroxybenzoic acids, C 6 H 4 \^ . The ortho variety of this is salicylic acid, an extremely important medicinal substance. Oxidation of the alcohol saligenin (above) yields salicylic acid. It may be prepared by a variety of reactions, the chief of which are as follows : (1) By saponifying methyl salicylate (oil of winter- green) with caustic potash, ,COO|CH COOK +CH 3 OH. OH OH The potassium salicylate thus formed can be decom- posed by acidifying with hydrochloric acid (see exp. 1, p. 366). (2) By subjecting sodium phenolate to the ac- tion of carbon dioxide under pressure (and at 140), sodium phenyl carbonate, CeHsOCOONa, is formed, which by heating to 140 in an autoclave, becomes converted into sodium salicylate (an intramolecular change taking place) : /COONa C 6 H 5 COONa = C 6 H 4 < MJH This method is used commercially. 364 ORGANIC CHEMISTRY (3) By fusing orthotoluene-sulphonic acid, ortho cresol, or orthosulphobenzoic acid with caustic potash. In the case of the first two bodies oxidation of the methyl side chain occurs. The replacement of the sulphonic group by hydroxyl has already been explained (cf. p. 337). (4) By converting orthoaminobenzoic acid into the diazonium salt and boiling this with water (see p. 384). Salicylic acid crystallizes in needles and melts at 159 (corrected). It is readily soluble in hot water, but only sparingly so in cold. Its aqueous solutions give an intense violet color with ferric chloride. It is readily soluble in fat-solvents. Solutions of salicylic acid possess antiseptic proper- ties, and, having no odor, it is therefore employed for preserving wines, foods, etc. Its sodium salt, /COONa CeH^ , has great medicinal value in the \OH treatment of rheumatism. There are also meta and para hydroxybenzoic acids, which can be prepared from the corresponding amino- or sulphonic-benzoic acids. They do not react with ferric chloride. The meta and para acids are weaker acids than salicylic acid, and have a somewhat different physi- ological action. The introduction of OH in the ortho position increases the acid power of the mole- cule, so that salicylic acid is much stronger than ben- zoic acid. Salicylic acid forms various salts, the salicylates, many of which are important. Methyl salicylate, AROMATIC ACIDS 365 /OH CeH^ , is the chief constituent of oil of XCOOCHs wintergreen. It can be made synthetically by heat- ing methyl alcohol with sulphuric acid and salicylic acid. A very interesting compound of salicylic acid /OH is phenyl salicylate, CeH 4 C< C 6 H 4 / / \OC-0 \OOCCH 2 X Both of the aspirins are invaluable substitutes for sodium salicylate. 368 ORGANIC CHEMISTRY Betol is the 0-naphthol ester of salicylic acid, C 6 H 4 (OH)COO.CioH 7 . B. Dihydroxybenzoic acid. Protocatechuic acid, /COOH (1) C 6 H 3 eOH (3) . X OH (4) /COOH Its monomethyl ether, C 6 H3^-OCH 3 , X OH is vanillic acid, which is derived from vanillin, the /CHO corresponding aldehyde, CeHs^-OCHs, by oxidation. X OH Vanillin, contained in the vanilla-bean, is extensively employed as a flavoring agent. It is used, with phloroglucin, as an indicator for free mineral acid (see p. 402). Synthetically it can also be prepared /OCH 3 by treating guaiacol, CH4V n ? with chloroform and caustic soda. C. Trihydroxybenzoic acid is the important com- COOH (1) OH (3) pound gallic acid, OH (4) (+H 2 0). This OH (5) is contained in certain plants, but is most readily obtained by boiling tannin with dilute mineral acid, or by fermenting oak gallnuts. Tannic acid (tannin), obtained from nutgall, consists of two molecules of gallic acid minus one molecule of water; it is therefore a condensation product. Tannic acid will be seen to bear a relation to gallic AROMATIC ACIDS 369 acid similar to that which disaccharides bear to monosaccharides : Ci 4 H 10 9 +H 2 =2C 7 H 6 5 . (Tannic acid) (Gallic acid) The following structural formulae have been pro- posed for tannic acid: H HO OH and OH >[COOH HO/ N H Hi JH -0 OC Its constitution is still under discussion. That gallic acid has the structural formula given to it above is proved by the fact that it can be prepared by fusing bromprotocatechuic acid with KOH: COOH OH OH |Br +K|OH =C 2 H 2 COOH OH +KBr. OH Gallic acid is almost insoluble in cold water, but soluble in hot water, alcohol, and ether; and with 370 ORGANIC CHEMISTRY ferric chloride its solutions give first a precipitate and then form a dark-green solution. A blue- black ink is made by adding gallic acid to a slightly acid solution of ferrous sulphate to which indigo carmine has also been added. When this dries on paper it oxidizes, giving a heavy black precipitate. When distilled, gallic acid yields pyrogallic acid and carbon dioxide (see p. 349). Airol and dermatol are combinations of gallic acid with bismuth. Tannic acid is much more soluble than gallic, the solution being colloidal. It gives the same reac- tion with ferric chloride. Tannic acid solution is slightly dextrorotatory. It has a very extensive commercial use in tanning, in which process it forms insoluble and tough compounds with the protein, etc., in skin. It is also employed, on account of its astringent properties, in medicine. Many de- rivatives of tannic acid have been prepared as sub- stitutes for it, such as tannalbin, tannacol, tannigen, tannoform, etc. There are many substances of vegetable origin similar in properties to tannic acid, but having dif- ferent chemical structure. These are classed to- gether as tannins. When acted upon by molten KOH some of these yield gallic acid, while others yield protocatechuic acid. The tannin of tea and that of coffee are not identical with tannic acid. EXPERIMENTS. (1) Test solutions of gallic acid and tannic acid with ferric chloride. (2) Add tannic acid solution to some gelatin solu- tion; the gelatin is precipitated. AROMATIC ACIDS 371 (3) To a solution of quinine bisulphate (quinine dissolved in very dilute H 2 SO4) add tannic acid solution; the quinine is precipitated. D. Other phenolic acids. Tyrosin is a phenol having an a amino acid side chain. It is parahydroxyphenyl-tf-aminoproprionic acid, /OH C6 KcH 2 .CHNH,COOH' ****** * ^^ from protein. Being a phenol it gives a test with Millon's reagent. Proteins that contain no tyrosin (as gelatin, certain albumoses, etc.) do not give this test. It occasionally occurs in the urine as charac- teristic crystals. Phenylalanin is closely related to tyrosin, differing only in not being a phenol; its formula is C 6 H 5 -CH 2 .CHNH 2 .COOH. Homo- gentisic acid is dihydroxyphenylacetic acid, /OH (5) C 6 H 3 ^-OH (2) . It has been found in the X CH 2 -COOH (1) urine in cases of alcaptonuria, being derived from tyrosin and phenylalanin. DIBASIC ACIDS In agreement with theory, there are three of these. They are called phthalic acids. Orthophthalic acid is prepared by oxidizing naphthalene (see p. 409) with sulphuric acid, or by oxidizing o-toluic acid with potassium permanganate. When heated it decom- poses into water and an anhydride, 372 ORGANIC CHEMISTRY which latter, when heated with phenol in the presence of H^SCU, yields phenolphthalein (see exp. 3), a body of complicated structure used ex- tensively as an indicator in volumetric analysis, being red in alkaline and colorless in acid solu- tion (see p. 399). It is also used now as a cathartic. The meta- and paraphthalic acids do not form anhydrides. Certain iodine derivatives of phe- nolphthalein, as nosophen, eudoxine, and antinosine, are used as medicines. When phthalic anhydride is acted upon by am- monia, an acid imide, phthalimide, C=O is formed. C = O EXPERIMENTS. (1) Heat some phthalic acid in a sublimation apparatus (see 'p. 13); the sublimate is phthalic anhydride. (2) To some phthalic anhydride add an equal quantity of resorcinol and 1 c.c. of concentrated H2S0 4 , then warm until deep red. Dilute with 100 c.c. of water and render alkaline with NaOH. The resulting solution of fluprescein is pinkish to transmitted light, but shows a marked greenish fluorescence to reflected light: C0\ /OH /C0\ =C 6 H 4 < >0+2H 2 \ v/ / HO-H,C 6 C 6 H 3 -OH ' O' (Fluorescein) AROMATIC ACIDS 373 (3) Mix equal quantities of phthalic anhydride and phenol, add a little C.P. H 2 SO 4 , and warm until strongly colored. Pour into a large quantity of water. This solution of phenolphthalein becomes red when it is made faintly alkaline : (C 6 H 4 OH)2+H 2 0. (Phenolphthalein) (4) Prepare eosin: To 2.5 gms. of fluorescein add 10 c.c. of alcohol, then add, a drop at a time, 2 c.c. of bromine, shaking the mixture after each addition. When enough bromine has been added .to form di- bromfluorescein, the latter goes into solution, then as tetrabromfluorescein is formed it crystallizes out. After the mixture has stood for an hour, filter and wash the crystals with a little cold alcohol. To a little of the eosin add NaOH solution; the eosin now dis- solves, forming a solution of characteristic red color. Eosin is an acid dye, being the potassium or sodium salt of tetrabromfluorescein, Br OH / CO \ / \Br There is a hexabasic acid, viz., mellitic, C 6 (COOH) 6 , which is present in the mineral mellite in combination with aluminium. CHAPTER XXVIII AROMATIC NITROGEN DERIVATIVES THERE is very little similarity between the nitro- gen compounds of the aromatic bodies and those of the paraffins. The nitro compounds of the paraffins we have seen to be of little importance; those of the aromatic bodies, on the other hand, are of prime importance, because they are readily produced and are easily converted into other nitrogenous deriva- tives. On this account nitration forms the first step in many organic syntheses. NITRO COMPOUNDS By shaking benzene in the cold with a mixture of pure nitric and sulphuric acids, mononitrobenzene, an oily liquid, is obtained. 1 The sulphuric acid absorbs the water produced: C 6 H 6 +HN0 3 = C 6 H 5 N0 2 +H 2 O Its boiling-point is 210, melting-point 5, and its 20 specific gravity 1.2033 at --^-. EXPERIMENT. To 80 c.c. H 2 S0 4 in a flask add, while shaking, 70 c.c. of colorless HNO 3 . Cool thor- 1 Mononitrobenzene has the odor of bitter almonds and is known as essence of mirbane. It is poisonous. 374 AROMATIC NITROGEN DERIVATIVES 375 oughly. Add (a little at a time) 20 c.c. of benzene, keeping the temperature of the mixture below 30 and shaking frequently. Take 30 minutes for the work of adding the benzene. Attach a vertical air- condenser tube; heat for' an hour in a bath kept at 60, shaking occasionally. Cool, dilute with 120 c.c. of water, pour into a separating funnel, draw off the bottom layer of acid, and wash the oil with water (the nitrobenzene becomes the bottom layer). Warm gently with dry calcium chloride in a flask on a water-bath. Distill in a fractionating flask; when the temperature rises above 100 attach an air-condenser, and observe the boiling-point. Note the odor of the distillate. If, on the other hand, the reaction be allowed to proceed at boiling temperature and with fuming nitric acid the product is dinitrobenzene, a crystal- line substance (needles) melting at 90 (corrected) and boiling at 297. /N0 2 C 6 H 5 N0 2 +HN0 3 = C 6 H 4 ^ N() +H 2 0. Although three varieties of this are possible, it is almost exclusively the meta form that is produced. EXPERIMENT. Prepare dinitrobenzene (meta). Mix in a beaker 25 c.c. of C.P. EUSC^ and 25 c.c. of fuming HNOs. Immediately add very slowly 5 c.c. of benzene from a pipette. After the action subsides, boil for a while and then pour the mixture into 250 c.c. of cold water. Filter off the precipitate, 376 ORGANIC CHEMISTRY press between filter-paper, and crystallize from alco- hol. Make a melting-point determination with dried crystals. Save a sample of the crystals. Toluene and the xylenes react with nitric acid in the same manner. In fact, the more alkyl groups there are attached to the benzene nucleus, the more easily can nitro groups be introduced into it. The nitro compounds are very stable. Trinitrotoluene has recently come into use as an explosive. AMINO COMPOUNDS The most important reaction of nitro compounds is that with nascent hydrogen, whereby they be- come converted into amino compounds, of which aniline (phenylamine) is the representative: C 6 H 5 NO 2 +6H = C 6 H 5 NH 2 +2H 2 O. (Aniline) Commercially, aniline is produced by mixing nitrobenzene with iron filings and hydrochloric acid in an iron cylinder provided with a stirring apparatus, and, when the action is over, adding lime and distilling the aniline. It is a colorless liquid boiling at 183.7 (corrected); its specific gravity" at 16 is 1.024. If not perfectly pure it becomes colored on standing. It is soluble in about 30 parts of water, and one part of water is soluble in about 20 parts of aniline at 25. It is readily soluble in alcohol. It gives several important color reac- tions, described in the experiments below. A blue coloring matter is produced by the action of AROMATIC NITROGEN DERIVATIVES. 377 potassium dichromate and sulphuric acid (see 2&); this is the same substance as the first artificial dye- stuff that was produced (in 1856). Aniline may be considered as NH 3 in which one H is displaced by C 6 H 5 . Like all such bodies (see p. 258), it directly combines with acids to form (aniline) salts, e.g., C 6 H 5 NH 2 .HC1; CeHsNHs.HNOs; C 6 H 5 NH 2 .H 2 SO4. The hydrochloride is technically known as aniline salt. In watery solution, however, aniline is not alkaline towards litmus and scarcely conducts an electrical current ; in other words, it does not become ionized (see p. 65). It is, therefore, quite different in this respect from aliphatic amines, which with water form bases, some of which are stronger even than ammonia (cf- p. 260). Phenyl (Cells) diminishes the basic properties of the amino (NH 2 ) group, but fatty residues increase the basic properties of NH 2 . Whereas nitrous acid decom- poses fatty amines with liberation of nitrogen (p. 260), it converts aromatic amines into diazonium compounds (p. 384). Aniline can be liberated from the acid in its salts by distilling with caustic alkali : C 6 H 5 NH 2 HC1 +KOH = C 6 H 5 NH 2 +KC1 +H 2 O. It can also be obtained by distilling indigo (hence its name, anil being the Spanish for indigo). It is an extremely important substance in organic synthesis. EXPERIMENTS. (1) Preparation of aniline. Put 30 gm. of granulated tin and 15 c.c. of nitrobenzene into a large flask, add gradually (in portions of 378 ORGANIC CHEMISTRY 5 c.c. each) 100 c.c. of C.P. HC1, and cool the flask whenever the action becomes very vigorous. When all the acid has been added, heat on a water-bath for one hour, using a vertical air-condenser. Now dilute with 50 c.c. of water, cool to room tempera- ture, pour into a separating funnel, and shake with ether to remove unchanged nitrobenzene. Add 50% NaOH until strongly alkaline; cool the flask if the mixture boils. Distill with steam, until the distillate comes clear. Add to the distillate 25 gm. NaCl for each 100 c.c.; shake in a separating funnel with three portions of ether. Dry the ether extract with solid potassium hydroxide. Next empty the liquid into a fractionating flask, distill off the .ether, then distill the aniline, using an air-condenser. (2) Tests, (a) Dissolve a little KC10 3 in 0.5 c.c. H2SO4; adding a few drops of aniline solution causes a blue- violet color to appear; diluting with water changes it to red; then adding ammonia restores the blue. (6) To a solution of aniline in EbSCU add a few drops of potassium dichromate solution; a blue color appears, (c) To some aniline solution (in water) add a filtered solution of bleach- ing-powder; a purple color develops. Derivatives of Aniline. The homologues include /CH 3 three toluidines, CeEU^ , of which the ortho \Nri2 and para varieties are important, and six xylidines, xca , this large number of isomers being due to differences in the relative positions of the AROMATIC NITROGEN DERIVATIVES 379 amino and methyl groups. When a mixture of ani- line and paratoluidine is treated with oxidizing agents, a compound known as para-rosaniline is obtained. Many of the aniline dyes are derivatives of this substance. Fucksin is methyl para-rosan- iline, CH 3 H 2 N Acid fuchsin is a sulphonic acid derivative. Dyes that have this structure are called the tri- phenylmethane dyes. EXPERIMENT. Heat together in a test-tube 1 c.c. of aniline, 1 gm. of paratoluidine, and 3 gm. HgCl 2 until dark red in color (15 minutes at 180-200). Cool partly, and extract with alcohol; a deep-red solution is obtained. Filter, and evaporate the filtrate. Replacement of one or more of the H atoms of the NEU group in aniline can be effected in various ways. By reaction with alkyl halides secondary and tertiary mixed aromatic fatty amines are obtained. 380 ORGANIC CHEMISTRY Thus methyl iodide produces methyl aniline and dimethyl aniline: C^ TT "\TTT ; TJ I T Y^TT C* TT "\TTT/' S -C N/ Ha. Lactophenin is lactylphenetidin, TT 2X15 OC-CHOH-CHa' AROMATIC NITROGEN DERIVATIVES 383 Phenocoll is aminoacetphenetidin (glycocoll phen- etidin). r H / OCzR5 4 \NH.OC-CH 2 -NH 2 ' Acid and ammo groups. By reducing the nitro- benzoic acids with tin and hydrochloric acid (nascent hydrogen) amino derivatives of benzoic acid may be obtained (cf. reduction of nitrobenzene to aniline, p. 376). The ortho variety of these is known as /COOH anthranilic acid, Csl&v -p. . It is produced as an intermediate product in the preparation of aniline by boiling indigo with caustic alkali. One of the most important nitrogenous aromatic compounds is an amine derivative of pyrocatechol. Epinephrin (adrenalin, suprarenin) has the follow- ing structural formula: CHOH CH 2 NH-CHs Epinephrin is the active principle in the extract from the suprarenal capsule, and when its solution is injected into the circulation of an animal, several important effects are observed, chief of which is rise of blood-pressure. It is optically active, 384 ORGANIC CHEMISTRY (a) D is -50.4 to 51.4. d. I. Suprarenin has been prepared synthetically. By treating this with tar- tar ic acid, crystals can be obtained, from which I. suprarenin is secured. This is found to be identical with natural epinephrin. Synthetic I. suprarenin is now a commercial product. It is advisable to reserve the term suprarenin for the synthetically produced substance. The physiological action of racemic suprarenin is weak compared with that of I. suprarenin, DIAZO AND DIAZONIUM COMPOUNDS When fatty amino derivatives are treated with nitrous acid (see p. 260), nitrogen is evolved and a hydroxyl group takes the place of the amino group; with the aromatic amines, on the other hand, nitrous acid at low temperatures has quite a different action. It converts them into diazo compounds, so called because they contain two nitrogen (nitrogen = azote (French)) atoms linked together. The diazonium salts are of very great importance in organic syn- thesis on account of the readiness with which they can be converted into other bodies. They are prepared by treating an ice-cold solution of an aniline salt with nitrous acid. The diazonium salts are believed to contain the linking N . +HN0 2 = (Benzene diazonium nitrate) AROMATIC NITROGEN DERIVATIVES 385 If a diazonium salt be dried and struck with a hammer, it explodes. Its important reactions are as follows: 1. With water it forms phenol and nitrogen: C 6 H 5 N 2 C1 +H 2 O = C 6 H 5 OH +N 2 +HC1. To obtain this result the diazonium salt is best pre- pared by treating a cold, acidified solution of an aniline salt with an equivalent quantity of sodium nitrite, and then boiling (see exp. 2, p. 338). 2. Boiling with alcohol causes replacement of the N 2 group either by ethoxy ( O C 2 Hs) or by hydrogen. In the first case phenyl ethyl ether or phenetole is formed : C 6 H 5 N 2 C1 +C 2 H 5 OH = C 6 H 5 OC 2 H 5 +N 2 +HC1 ; in the second case benzene and aldehyde: C6H 5 N 2 C1+C 2 H 5 OH= C 6 H 6 +CH 3 CHO +N 2 +HC1. 3. Heating with a halogen acid or, better still, with an acid solution of the corresponding cuprous salt of the acid causes replacement of the N 2 group by the halogen: C 6 H 5 N 2 C1 +HC1 = C 6 H 5 C1 +N 2 +HC1. 4. Heating with cuprous cyanide replaces the N 2 group by cyanogen: C 6 H 5 N 2 Cl+Cu 2 (CN) 2 = C 6 H 5 CN+Cu2<^ +N 2 , 386 ORGANIC CHEMISTRY and the resulting nitrile can be hydrolyzed to form benzole acid (see p. 356). 5. Nascent H changes- a diazonium salt to phenyl- hydrazine (p. 388). Other replacements by hydrocarbon residues, sulphur groups, etc., can also be effected. EXPERIMENTS. (1) Prepare benzene diazonium nitrate. Put 50 gm. of arsenic trioxide into a flask; provide a funnel- tube, as in other gas-gen- erators, and a delivery-tube which is connected with an empty bottle or cylinder standing in cold water. Mix 10 gm. of aniline nitrate with 12 c.c. of cold water in a graduate or large test-tube standing in ice-water, and immerse in the liquid a delivery-tube coming from the condenser-bottle of the gas appara- tus. Through the funnel add 50 c.c. of concentrated HNOa to the As20s; heat as is necessary to keep up an evolution of nitrogen oxides. Bubble the gas into the aniline nitrate mixture until complete solution is secured. Add to the solution an equal volume of alcohol cooled to 0, then some cold ether. An abundant precipitate of benzene diazonium ni- trate is obtained. 1 Filter quickly with suction. Test for the following reactions at once: (2) (a) Dissolve some in water and let it stand. It 1 A less troublesome method of preparation is as follows : dissolve 5 gm. aniline hydrochloride in 35 c.c. absolute alcohol which contains a few drops of concentrated HC1. Cool to 5; add 4 c.c. ethyl nitrite very slowly while shaking and cooling. Test for HN0 2 with starch iodide paper. Add more ethyl nitrite if necessary. Let it stand a while, then add cold ether. AROMATIC NITROGEN DERIVATIVES 387 decomposes, as is shown by change of color. (6) Boil some with water; notice the phenol odor, (c) Boil some with alcohol in a test-tube; it is de- composed with production of phenetole. (d) Add some to a little concentrated HCt and boil. Chlor- benzene is formed : on adding water this sinks to the bottom, (e) The dried salt is explosive; place a small particle on a piece of iron and strike it with a hammer. In all the above cases the N 2 group is replaced. Diazo compounds, however, exhibit another type of reaction in which the N 2 group is retained and a new substance of greater stability is produced. The more important of these substances are : a. Diazoamino Compounds. In these, one of the hydrogens of an amino group is replaced by a diazo residue. A type of the class is diazoaminobenzenej C 6 H 5 N=N NH C 6 H 5 , which is prepared by bring- ing together aniline and diazonium chloride in neutral solution. It forms yellowish crystals, which are in- soluble in watei but soluble in alcohol. By heating with aniline, and in various other ways, diazo- aminobenzene becomes converted by a rearrange- ment of atoms into 6. Aminoazobenzene , CeHs N=N CeH* NH2, which is the amino derivative of a substance called azobenzene. Dimethylaminoazobenzene is a derivative, having the formula, 388 ORGANIC CHEMISTRY It is used as an indicator for free acid, giving a pink color in the presence of the latter (see p. 402). c. Azobenzene, CoHs N r =N CeEU. Azobenzene can be obtained by partial reduction of nitroben- zene. It forms orange-red crystals and is soluble in water, but the resulting solution is not a dye (see p. 407). The azo group is present, however, in many dyes. It has been calculated that the number of azo dyes that can theoretically be prepared runs up into the millions. d. Hydrazobenzene, C 6 H 5 NH NHC 6 H 5 , is ob- tained by reducing azobenzene; it is colorless. Hy- drazobenzene is the diphenyl derivative of hydrazine, NH 2 NH 2 . Benzidine is produced from hydrazobenzene by the action of strong acids, the latter causing intra- molecular rearrangement, Its formula is e. Phenylhydrazine, CeHsNH NH 2 , is the most important hydrazine derivative. It forms hydra- zones (see p. 352) with aldehydes, and osazones with sugars (see p. 235). It is obtained by reduc- tion of diazonium salts (see exp.) : C 6 H 5 N 2 C1 +4H = C 6 H 5 NH NH 2 HC1. (Phenylhydrazine hydrochloride) EXPERIMENT. To 18 c.c. of freshly distilled aniline add, while stirring, 100 c.c. of concentrated HC1. Cool in a freezing mixture to 0, add 150 gm. of ice, then add slowly from a dropping funnel (have AROMATIC NITROGEN DERIVATIVES 389 the tip dipping in the mixture), while shaking, a solution of sodium nitrite (14 gm. in 70 c.c. of water), until testing with starch-potassium-iodide paper shows the presence of free nitrous acid (blue color). For the test dilute a drop of the acid mixture with 5 c.c. of water. During the diazotizing the tempera- ture must keep below 5. Add slowly an ice-cold solution of 60 gm. of stannous chloride in 50 c.c. of concentrated HC1. Add ice to keep the temper- ature at 0. Mix thoroughly and let it stand one hour. Filter through muslin, using suction. Trans- fer to a porous plate, press out the phenylhydrazine hydrochloride crystals in a thin layer, and set away to dry out: 1. C 6 H 5 NH2-HC1+HN02 = C 6 2. C 6 H5N 2 CH-4H=C 6 H 5 NH.NH 2 .HC1. Free phenylhydrazine may be extracted by treat- ing the hydrochloride with an excess of NaOH solution and shaking with ether. After dehydrating the ethereal extract, evaporate the ether; phenyl- hydrazine remains behind as a liquid which readily solidifies on cooling. Phenylhydrazine is a colorless oil at ordinary temperature and boils at 242, meanwhile under- going some decomposition. It melts at 19. It is poisonous. It becomes dark colored on exposure to air. Its salts, e.g., the hydrochloride, are solid and are sometimes employed in place of the base itself for producing osazone crystals, the hydrochloric acid being neutralized by sodium acetate. 390 ORGANIC CHEMISTRY The relationship of these bodies to nitrobenzene and aniline will be evident from an examination of the following formulae: C 6 H 5 -N CeHs-NH C 6 H 5 -NH C 6 H 5 N0 2 | | C 6 H 5 NH 2 (NHroben- C 6 H 5 'N C 6 H 5 'NH NH 2 (Aniline > (Azoben- (Hydrazo- (Phenylhydrazine) zene) benzene) CHAPTER XXIX SULPHUR AND ARSENIC DERIVATIVES SULPHUR DERIVATIVES Sulphonic acids. With sulphuric acid the ben- zenes form sulphonic acids, thus: C 6 H 6 +H 2 S0 4 = C 6 H 5 S0 3 H +H 2 O (Benzene-sulphonic acid) /CH 3 and C6H.CHs+H2S04=CH4< Qr ._+H a O. ^feUsxl (Toluene-sulphonic acid) It is of importance to note that in this respect they behave quite differently from paraffins. When an alkyl group (as in toluene), an amino group (as in aniline), or a hydroxyl group (as in phenol) is attached to the benzene nucleus, the sulphonic acid derivative is more easily formed than when benzene alone, or any of its 6ther derivatives, is used. The sulphonic acids are soluble in water and are strong acids, so that their salts are very stable, e.g., CeHsSOsNa. Treated with phosphorus pentachlor- ide the salts of sulphonic acids form sulphonic chlorides, which may be reduced to mercaptans: = C 6 H 5 S0 2 C1 +POC1 3 +NaCl. 2. C6H5S0 2 C1+6H=C6H 5 SH+HC1+2H 2 O. (Th'iopnenol) 391 392 ORGANIC CHEMISTRY These reactions show us that sulphonic acids must possess an OH group and that the S atom is in immediate connection with the benzene ring. The structural formula of benzene-sulphonic acid O TT must therefore be jjQ_!\gQ or sulphuric acid, y>S0 2 , in which one hydroxyl group is replaced by phenyl (cf. p. 306). They give several other reactions, the following of which are important : 1. Fused with potassium hydroxide, benzene-sul- phonic acid yields phenol, C 6 H 5 S0 3 K +KOH = C 6 H 5 OH +K 2 S0 3 . EXPERIMENTS. (1) To 75 gm. of fuming EhSC^ in a small flask to which an air-condenser is attached add, a little at a time, 20 gm. of benzene, shaking and cooling after each addition. Transfer to a dropping funnel, and run the mixture out, drop by drop, into 300 c.c. of cold saturated NaCl solution. Keep the salt solution cold with ice-water. On standing, crystals of sodium benzene sulphonate form. Crystallization may be hastened by strongly cooling some of the mixture in a test-tube and emptying the crystalline mass into the main liquid. Filter the pasty mass of crystals with suction and wash it with a little saturated salt solution. Press dry, and complete the drying in an oven at 110. (2) Weigh the dry powder (of 1); weigh out five times as much KOH. Put the KOH in an iron dish, add a few cubic centimeters of water, SULPHUR AND ARSENIC DERIVATIVES 393 and melt. Then add slowly, while stirring with a spatula, the sodium benzene sulphonate. Keep fused for an hour. Dissolve in water, acidulate with HC1, shake with ether, and treat the ethereal solution of phenol in the same way as in the pre- vious phenol experiments (see p. 338). 2. Distilled with potassium cyanide, cyanides are formed : C 6 H 5 S0 3 K+KCN =C 6 H5CN+K 2 S03 /CH 3 /CH 3 and C 6 H 4 <+KCN=C6H4< +K 2 S0 3 . By hydrolysis these cyanides can be converted into acids : C 6 H 5 CN+2H 2 =C 6 H 5 COOH+NH 3 . The toluene-sulphonic acids may be ortho or para. The meta variety is rare. The sulphonic acid group is present in many dyestuffs (see p. 407). By the action of sulphuric acid on salicylic /COOH (1) acid, salicyl-sulphonic acid, CH4\ , is MjSO 3 H (2) formed. This is a white crystalline deliquescent substance, readily soluble in water, the solution being a valuable precipitant for certain proteins. Its solutions on standing become colored red. Phenol and sulphonic groups exist in phenol-sul- /S0 3 H phonic acid, CeH^ (o or p), which is commer- cially known as aseptol and used as a disinfectant. 394 ORGANIC CHEMISTRY The sodium salt of it is sodium sulphocarbolate (phenolsulphonate), and is used to arrest fermenta- tion in the stomach. Acid and sulpho groups. Metasulphobenzoic acid is produced by the action of sulphuric acid on ben- zoic acid. The important substance saccharin is the imide of orthosulphobenzoic acid, XX) \ C6H < SO > H ' , and is also called benzosulphinide. Its sodium salt (in which Na replaces H of NH) is called soluble saccharin. It is intensely sweet, and anti- septic; on account of these properties it is used as a medicine and a preservative. Sulphonic and amino groups. By the action of sulphuric acid on aniline, aniline sulphate is formed, and then this becomes converted by heating into paraminobenzenesulphonic acid or sulphanilic acid, /NH 2 < _ , by dehydration: N^Os-U C 8 H 5 NH 2 H 2 S0 4 = C 6 H 4 < ' +H 2 O. Sulphanilic acid is soluble in hot water, but only sparingly so in cold water. Its solution is acid in reaction, thus differing from that of taurin (amino- ethyl-sulphonic acid, see p. 272). It is used in the manufacture of dyes, in a large number of which there exists the sulphonic acid group along with a diazo group. Two of these dyes, viz., methyl SULPHUR AND ARSENIC DERIVATIVES 395 orange and tropaeolin OO, are used as indicators in biochemistry. EXPERIMENT. Preparation of sulphanilic acid. To 50 gm. of C.P. IbSCU in a flask, add gradually 15 c.c. of aniline, and heat in an oil-bath at 180-190 for about four hours, until a test-drop, diluted with water and treated with NaOH, shows no unchanged aniline. Cool, and pour into a beaker of cold water while stirring the latter. Filter off the crystals. Evaporate the nitrate to small volume to secure more crystals. Recrystallize from hot water. Helianthin is dimethylaminoazobenzene-sulphonic acid, ,N= N C 6 H4N(CH 3 )2 (1) C6H4 \S0 3 H (4) prepared by acting on benzene-diazonium-sulphonic acid with dimethylaniline. Its sodium salt is methyl orange (see indicators, p. 400). Orange II is an azo dye, somewhat related to methyl orange in chemical structure: /N= N -doEe -OH C6H4 \S0 3 H EXPERIMENT. Dissolve 10 gm. of dry sulphanilic acid in 100 c.c. of 2.5% Na2COs solution (made with anhydrous carbonate), and add 3.5 gm. of NaNO 2 dissolved in 20 c.c. of water. Cool with ice-water, gradually add diluted HC1 (6 c.c. +10 c.c. H 2 O), and finally add an acid solution of dimethylaniline 396 ORGANIC CHEMISTRY (6 gm. +6 c.c. HC1 +20 c.c. H 2 O). Render the mix- ture alkaline with NaOH solution and add 20 gm. of NaCl. Filter off the methyl orange precipitate and crystallize from hot water. To a little dilute solution of methyl orange add some acid, a red color is obtained. Save a sample of the crystals. Tropseolin OO is diphenyl-aminoazobenzene-sul- v, M n TT /N 2 -CeH 4 NHC 6 H5 phonic acid, C 6 H 4 < . Its solu- tion gives a violet color with free mineral acid; or, if its alcoholic solution be evaporated to dryness, the resulting residue, gives a violet color with free mineral acids. Applied in this latter manner the test is very delicate. It is thus used as an indicator in analysis of the gastric juice. Methylene blue (methylthionin chloride) is a dye containing sulphur in the chromophore group (see p. 406). It is a thiazine derivative, its formula being: /\/ N \. AROMATIC ARSENIC DERIVATIVES An arsenic-containing derivative of ortho amino- phenol has been recently synthesized. It is used as a remedy for syphilis. Its trade name, salvarsan (arseno-benzol or " 606 ")> gives little idea of its SULPHUR AND ARSENIC DERIVATIVES 397 composition. It is the hydrochloride of dihydroxy- diamino-diarseno- (di-) benzene, NH 2 Another organic arsenic compound is atoxyl, in which an OH of monosodium arsenate is replaced by aniline, /NH 2 (1) \AsO(OH) (ONa) (4)' If the sodium be substituted by H, arsanilic acid is obtained. Arsacetin is sodium acetyl arsanilate. CHAPTER XXX QUINONES, DYES AND INDICATORS Quinones. These may be regarded as diketones. The best known of them is benzoquinone or quinone, / co \' HC CH which has the structural formula || || , and HC CH \CO/ may be prepared by oxidizing various para deriva- tives of benzene, but not ortho or meta derivatives. Thus p-phenolsulphonic acid, p-sulphanilic acid, p-amino-phenol, etc., all yield quinone when oxidized. It is usually prepared, however, by oxidizing aniline with chromic acid or by oxidizing hydroquinol: COH C=0 \ /\ C HC CH HC CH | || +0= || || +H 2 0. HC CH HC CH v COH These reactions for its preparation (with the exception of its preparation from aniline) leave little doubt as to its structural formula. The quinones are of a yellow color and possess a 398 QUINONES, DYES AND INDICATORS 399 pungent odor. In some particulars they behave like ketones, but in others very differently. They have oxidizing properties and are important in dye chemistry. INDICATORS At this stage it will be convenient to discuss briefly the theory of the action of indicators. These must possess weak acid or basic properties, and be, therefore, undissociated when in a free state, but dissociated when present as salts. In the dis- sociated state the anion must have a different color from that of the undissociated compound. Taking the three most commonly used indicators, phenolphthalein, methyl orange, and litmus, let us see in how far their actions can be thus explained. (1) Phenolphthalein. This is of the nature of a very feeble acid, so that it is undissociated when in a free state, and when undissociated it is colorless. When dissociated, however, its anion has a red color. Dissociation occurs when it is converted into a salt. Thus, when we titrate an acid with sodium hydrox- ide, using phenolphthalein as indicator, what happens is this: In the presence of the acid the phenolphthalein is undissociated, and the solution is therefore colorless; as alkali is added the acid becomes gradually neutralized, until at last a trace of alkali in excess of that necessary to neutralize the acid is present; this trace combines with the phenolphthalein, forming a salt, which then dissoci- ates, so that the anion imparts its red color to the solution. 400 ORGANIC CHEMISTRY The acid to be titrated must be distinctly stronger than phenolphthalein, for otherwise, before the former has all been neutralized, some of the salt formed will become hydrolyzed (see p. 70), and the base thus liberated will combine with the phenol- phthalein and form a salt which, partially dissociat- ing, will impart a pink tint to the solution. Thus, phenols cannot be titrated with phenolphthalein. On the other hand, such a feeble acid as carbonic is so much stronger than phenolphthalein that the latter can be employed as an indicator for titrat- ing it. On this account carbon dioxide (carbonates) must be absent from the standard alkali used for titrating. Phenolphthalein can also be used for practically all organic acids. The base used for neutralization must also be a strong one. Thus, if a feeble base such as ammonia is employed, then the salt which it forms with the phenolphthalein will be so feeble that it will be decomposed by the water (hydrolysis), and the end reaction will be indefinite, an excess of ammonia requiring to be present before the decomposing effect of the water is overcome. Phenolphthalein must not, therefore, be used when ammonia or ammonium salts are present in a solution. Phenolphthalein is the ideal indicator for weak acids and acid salts, and should be employed along with a strong base. (2) Methy 1 Orange. This is the sodium salt of a much stronger acid than phenolphthalein, and it dissociates readily in weak solution. When un- dissociated (as free acid) it is red, when dissociated QUINONES, DYES AND INDICATORS 401 (as a salt) its anion is yellow. Its dissociation in water is prevented by the presence of a trace of stronger acid such solutions are therefore red but if alkali is added in sufficient amount just to neutralize this acid, then the methyl orange partially dissociates and the solution becomes much paler, and if a trace more alkali is added, still more dissocia- tion occurs, so that the solution becomes bright yellow. Methyl orange is not affected by acid sodium phosphate (NaH 2 PO 4 ), so that a weak acid such as this must be present in large excess before it can prevent the dissociation of methyl orange; therefore, for titrating acid salts this indicator is unsuitable; and for the same reasons it cannot be used for weak organic acids. On the other hand, it is suitable for practically all bases and carbonates, since with all of them it will immediately form dis- sociable salts, which do not hydrolyze so long as any of the base is available (i.e., uncombined with the acid that is being titrated, which must, of course, be stronger than methyl orange). Nitrous acid acts on methyl orange chemically, therefore nitrites must not be present. Methyl orange is therefore especially useful for the titration of bases, including ammonia, and un- suitable for the weaker organic acids. Very weak organic bases (as aniline) cannot be titrated. According to a recent theory the color change of phenolphthalein and methyl orange is due to intra- molecular rearrangement and production of a tau- tomer having a quinoid structure (a CH group of benzene changed to CO). For example, the red 402 ORGANIC CHEMISTRY salt of phenolphthalein (in the presence of dilute alkali) is said to have the following quinoid formula : Compare this with the formula of non-ionizing phenolphthalein (p. 373). It is supposed that methyl orange has a tautomeric quinoid structure in the presence of free acid. The quinoid substance is red in the case of both phenol- phthalein and methyl orange. The indicators used for the detection of mineral acid in the gastric contents belong to the same class as methyl orange, e.g., Congo red (p. 410) and dimeth- ylaminoazobenzene (p. 387). While it is true that these indicators will not give an accurate titration value with organic acids, our experience (contrary to statements in clinical chemistry textbooks) is that methyl orange, Congo red, and dimethyl- aminoazobenzene give a distinct color reaction (as with mineral acids) even when used with very dilute organic acid solutions (see exp. p. 405). The phloroglucin- vanillin reagent (p. 348), however, reacts only to mineral acid and can be used as the indicator when making a quantitative estimation of mineral acid in the presence of organic acids. (3) Litmus. This stands between phenolphtha- lein and methyl orange in its properties. In the QUINONES, DYES AND INDICATORS 403 un-ionized state it is red, therefore red with acids; and in the ionized state blue, therefore blue with alkalies. The importance to the student of thoroughly understand- ing the action of these three indicators will be evident from a single illustration, namely that urine reacts very differently towards them. Towards methyl orange urine (even when it is acid to litmus) reacts alkaline or neutral, towards phenol- phthalein it reacts acid, while towards litmus paper urine reacts acid (usually), neutral, or alkaline. The cause of this difference in action lies in the fact that in this fluid we have a mixture of NaH 2 P0 4 and Na 2 HP0 4 . Occasionally these two salts are present in equivalent quantities in the urine (normally in milk also) ; in such a case the urine reacts acid to blue litmus paper and alkaline to red litmus (amphoteric reaction). This is due to the fact that NaH 2 P0 4 is acid to litmus, and Na 2 HP0 4 is alkaline. In normal (acid) urine NaH 2 P0 4 preponderates over the alkaline salt, therefore the urine reacts acid to litmus. Even the acid-reacting NaH 2 P0 4 , is but feebly dissociated (i.e., furnishes few ions) compared with the relatively strong acid in methyl orange; therefore it is unable to influence the degree of dissociation of methyl orange. Congo red acts in the same manner as methyl orange. Phenolphthalein, however, is so feeble an acid that these acid salts can readily keep it in the (practically) undissociated condition and do not allow the indicator to form its sodium salt, under which circumstances, as we have already stated, it remains colorless. EXPERIMENTS. (1) Effect of ammonium salts on indicators, (a) Measure with a pipette 5 c.c. of decinormal E^SCU containing ammonium sulphate and titrate with decinormal NaOH, using methyl orange as indicator. (6) Repeat (a) but use phe- nolphthalein as indicator. (2) Organic acids, (a) Titrate 5 c.c. of decinormal 404 ORGANIC CHEMISTRY butyric acid with methyl orange; (6) with phenol- phthalein. (3) Acid salts, (a) With litmus paper (both blue and red) test solutions of NaH 2 P04 and Na 2 HP04 (both being one-tenth gram molecular), then mix 4 c.c. of NaH 2 PO 4 with 6 c.c. of Na 2 HP0 4 , and test with litmus (amphoteric) . (6) Test the acidity of acid phosphate to methyl orange and to methyl red. Determination of the H ion concentration of a solution may often be made by the use of indicators. This depends on the fact that different indicators suffer a color change in the presence of different degrees of acidity; thus rosolic acid gives a series of colors from yellow to red when added to various solutions of low acidity, solutions of somewhat greater acidity give colors with methyl red rang- ing from red to yellow, still more acid solutions give similar color changes with methyl orange, while N N with solutions equivalent to HC1 Tropseolin 1UU oUU 00 gives a gradation of colors from red to yellow (see exp. 1). By using standard solutions of known H ion concentrations and adding the proper indicators, a basis is secured for colorimetric estimations. To the solution to be tested is added an indicator which gives with the solution one of the intermediate colors shown by the standard solutions to which the same indicator has been added. It may be necessary to try several indicators before the right one is found. The final determination is simply a QUINONES, DYES AND INDICATORS 405 question of color matching; and the solution is said to have the same H ion concentration as the standard solution that most nearly resembles it in color. EXPERIMENTS. (1) Select 12 test-tubes having practically the same diameter, and clean them thoroughly, rinsing with distilled water. Arrange them in three series of four tubes each. In each tube put 10 c.c. of the acid solution indicated. For series 1 use |, A, ^, and JL HCt. For series 2 use A, _*L, _*_ and J^ lactic acid. For series 3 use -j^ ^L, gH_, and -^ l act ic acid. To each tube of series 1 add 5 drops of .05% tropseolin OO (dissolved in 50% alcohol) ; for series 2 use 3 drops of .05% alcoholic solution of dimeth- ylaminoazobenzene ; and for series 3 use 3 drops of .02% methyl orange. After mixing note the gradation of colors obtained in each series. (2) In order to illustrate the differing H ion concentrations obtained at the end-points of titra- tion with different indicators, titrate successively 5 c.c. portions of one-tenth gram molecular NaEbPC^ solution, using methyl red, rosolic acid, and phenol- phthalein. Explain why the titrations differ so widely. 406 ORGANIC CHEMISTRY DYES Several of these have already been mentioned. All such bodies are supposed to owe their dyeing properties to the presence in them of a so-called chromophore group. Most chromophore groups contain double link- ings. The azo group (N=N) is an independent chromophore, being sufficient of itself to impart color to a compound. The groups C = 0, CH = CH and N=C are dependent chromophore constituents, since they require a certain environment in the struc- ture of the molecule in order to enable them to impart color; the true chromophore group in these cases must, therefore, be more than the simple groups given above. The following give illustra- tions of chromophore groups: CO CO QUINONES, DYES AND INDICATORS 407 The presence in a substance of one of these groups alone is not, generally, sufficient to constitute it a dye, the substance is merely a chromogen; certain other groups, such as OH and NEb, must, as a rule, be attached to a chromophore-containing com- pound to render it available as a dye. These assisting or auxiliary groups are called auxochromes; these confer salt-forming properties. The auxo- chrome has the effect of producing color in color- less chromogens, or of intensifying the color of other chromogens. The dye-stuff, when fully elab- orated, will have basic or acidic properties. The sulphonic acid group is often introduced to render a dye soluble (and acidic). In solution some dyes are emulsoid colloids, a few are semi-colloids, and others are crystalloids. The diffusible dyes can penetrate animal tissues, and, therefore, can be used as stains in the prep- aration of tissues for microscopical examination. The semi-colloids dialyze slowly, probably because a very small proportion of the substance is in true solution in equilibrium with that portion that is in colloidal solution. If cloth is immersed in water its fibers acquire negative charges of electricity. Dyes that furnish electro-positive ions or electro-positive colloidal particles are adsorbed by the fibers, because the ions or particles are attracted, and after neutraliza- tion of electrical charges are precipitated on the fibers (see p. 95). In many cases the amount of dye taken up from a solution of a particular concen- tration indicates that there is an equilibrium be- 408 ORGANIC CHEMISTRY tween the fibers and the solution; this is the same sort of result as is obtained in recognized adsorption processes. Dyes that have electro-negative ions or colloidal particles may be adsorbed by fibers under special conditions, for instance, when elec- trolytes are present. Basic dyes are salts of weak organic bases with strong acids, and, therefore, undergo hydrolytic dissociation (see p. 70). The base set free goes into colloidal solution, the particles being electro- positive. Acid dyes are mostly sodium salts of fairly strong organic acids; they do not hydrolyze appreciably, but they ionize. The ion of the acid (electro-negative) behaves like a colloid. In the case of many dyes cotton fibers do not take up the color satisfactorily. Mordants are used as a preliminary step in the dyeing process, resulting in the coating of the cotton fibers with a colloidal substance which is capable of precipitating or adsorb- ing the dye substance. For basic dyes tannic acid is largely used. For acid dyes acetates of aluminium, chromium, and iron are commonly employed, the cloth being soaked with the acetate and then steamed to decompose the salt and leave the colloidal hydroxide of the metal. In some cases the dye may enter into chemical combination after adsorption. CHAPTER XXXI AROMATIC COMPOUNDS HAVING CONDENSED RINGS Naphthalene (CioH 8 ) contains two benzene rings connected in the following manner: CH HC It forms white crystals melting at 80, boiling at 218.1 and having a tar-like odor. It is volatile and is contained in coal-gas, being also a con- stituent of the distillate from coal-tar. It is an antiseptic. EXPERIMENTS. (1) Heat some naphthalene in a sublimation apparatus. (2) Try the reaction with aluminium chloride given by some naphthalene dissolved in chloroform (see p. 332). The naphthols, CioHr- OH, correspond to phenols. Alpha-naphthol (melting-point 95) and beta-naph- thol (melting-point 122) are both of importance. 409 410 ORGANIC CHEMISTRY a Derivatives of naphthalene have some group introduced in position 1, 4, 5 or 8, while derivatives have it in position 2, 3, 6 or 7. Ortho, meta and para naphthalene derivatives have two substituting groups attached to the same half of the formula (as inpositions 1, 2, 3, 4). Epicarin is /3-naphthol-ortho-hydroxy-toluic acid, /COOH C 6 H 3 eOH x CH 2 -OCi H 7 /3-Naphthol benzoate, d H 7 OOC-C 6 H 5 , is an- other of the newer remedies. Orphol is bismuth /3-naphtholate. All these sub- stances are antiseptics. Alpha- and beta-naphthylamines, CioHr-NEk are used as reagents. a-Naphthylamine is used to detect the presence of and to estimate the amount of traces of nitrites, as in drinking water. This test depends on the fact that a red compound, azo-benzene- naphthylamine-sulphonic acid, is produced. Congo red is a complex diazonium derivative of naphthylamine-sulphonic acid. Its formula is Its color becomes blue in the presence of free acids. It forms a colloidal solution, which will not dialyze. Electrolytes cause its molecules to aggregate. Santonin, CisHigOs, is a naphthalene derivative and is the inner anhydride or lactone of santonic acid. Its formula is probably, ANTHRACENE C_CH 3 CH 2 411 CH CH 3 CH 2 Elaterin, a neutral principle, is said to be a deriva- tive of naphthalene. Anthracene. CuHio, is a hydrocarbon contain- ing three benzene rings condensed together: CH CH CH or It occurs in coal-tar in small quantity and is used in manufacturing alizarin. Its crystals melt at 216.5 (corrected). Exposure to light changes it into dian- thracene, which depolymerizes in the dark to anthra- cene, a reversible photo-chemical reaction: ^ C28-H20* 412 ORGANIC CHEMISTRY One of the important derivatives of anthracene is anthraquinone, CH CO Dihydroxyanthraquinone is the very important dye alizarin, Ci4H 6 2 (OH)2: CH CO COH COH H CH CO This was formerly obtained from a plant. It is now produced much more cheaply by synthetic means. Its synthesis on a commercial scale is one of the great achievements of organic chemistry. Aloin is an anthraquinone derivative. Its formula may be (the position of the OH being uncertain) : CH CO HO-C C-CH 3 CH 3 CH(CHOH) 3 CHO PHENANTHRENE 413 Chrysophanic acid, Ci4H 5 02(CH 3 )(OH)2, and chrysarobin, Ci 5 H 12 03, are anthracene derivatives of therapeutic importance, chrysophanic acid probably being monomethyl-dihydroxy-anthraquinone, and chyrsarobin monomethyl-trihydroxy-anthracene. Emodin, CisHioOs, is 2-monomethyl 3, 6, 7-tri- hydroxyanthraquinone. Rhein, CisHsOe, is also an anthraquinone deriva- tive, /COOH (1) (3) . X OH (5) Isomeric with anthracene is phenanthrene, CH CH Some chemists think that it may be a derivative of diphenyl, the two benzene rings being linked to CH =CH, in addition to the direct linking, the form- ula being written: CHAPTER XXXII HETEROCYCLIC COMPOUNDS HETEROCYCLIC compounds are related to the aromatic compounds, but contain at least one atom other than C atoms in the ring; this is generally N. 1 Pyrrol has the formula HC CH. lodol is a HC CH NH medicinal derivative; it is tetraiodopyrrol. 1 Heterocyclic compounds of minor importance are thiophene, HC CH HC CH' \/ s pyrazole, HC CH HC NH \/ NH imidazole, HC N YH and furan, HC CH v 414 HETEROCYCLIC COMPOUNDS 415 Pyrrolidine is the hydrogen addition derivative of pyrrol, EbC 3 4 CH2. This is the basis of certain alkaloids. H 2 C 2 5 CH 2 NH Prolin and hydroxy-prolin are pyrrolidine acids (p. 271). Haematin, haemin, and haematoporphyrin (from haemoglobin) are supposed to contain four pyrrol rings in their molecules. Antipyrin or phenazone is an important derivative of pyrazolone, which contains the pyrazole ring, its formula being : CH 3 N CH 3 . N C 6 H 5 It is an antipyretic of value, and is a crystalline substance melting at 113. Two of its derivatives are used as remedies: pyramidon or dimethylamino-antipyrin, and tussol or antipyrin mandelate. Furfuraldehyde is the chief derivative of furan; its formula is HC=CH I > HC=C^-CHO. Pyridine Bases. These are ammonia deriva- tives and of great importance on account of their relationship to certain alkaloids which will be dis- 416 ORGANIC CHEMISTRY cussed presently. The simplest member of the series is pyridine, which has the structural formula, CH HC/NCH . It may therefore be considered as 'CH N benzene with a CH group replaced by nitrogen (C 5 H 5 N). There are several methyl pyridines. The pyridines are contained in coal-tar, and are formed when bones are distilled, being produced by the action on one another at high temperatures of acrolein, ammonia, methylamine, etc. Pyridine is a colorless liquid with an odor like tobacco-smoke. It boils at 115 C. It mixes readily with water, the resulting solution being strongly alkaline. Like other tertiary ammonia bases, it directly combines with acids to form crystalline salts. When it is warmed with alkyl halides, addition products are formed, and if these be treated with caustic potash a very pungent and disagreeable odor is evolved. EXPERIMENTS. (1) Dissolve some pyridine in water; test alkalinity with litmus. Notice the odor. (2) Then neutralize the solution with HC1, add a few drops of platinic chloride solution, and boil; a yellow precipitate of (CsHsN^PtCU forms. HETEROCYCLIC COMPOUNDS 417 CONDENSED HETEROCYCLIC BENZENE COM- POUNDS PYRROL DERIVATIVES OF BENZENE / Indol, C 6 H 4 < /CH, contains the pyrrol nucleus, condensed with the benzene nucleus, and may be represented thus : CH CH CH NH Skatol is methyl indol, C 6 H 4 <^ ^CH. Indol and skatol are contained in faeces, imparting the characteristic odor to the latter. They are pro- duced in the intestine by the action of bacteria on the aromatic groups (tryptophan) in protein. They are volatile with steam. Indican is the oxidation product of indol in com- bination with sulphuric acid as an ethereal sulphate, / C ^-0 S0 2 (OK) CeH^ \CH . It is potassium in- doxyl-sulphate. It is sometimes present in the urine in considerable quantity. The urine may also contain indoxyl glycuronic acid. The origin of these 418 ORGANIC CHEMISTRY bodies is indol absorbed from the bowel-contents. Indigo can be obtained from it; and indigo is de- posited from urine containing much indican after ammoniacal decomposition sets in. To estimate the indican in the urine it is converted into indigo by various reagents, and this is then removed by shaking with chloroform. The blue chloroform solution can be compared with an indigo solution of known strength, and thus a colorimetric estima- tion may be made. Skatoxyl-sulphuric acid is the corresponding r^ _ OTT derivative of skatol, C 6 H 4 / C S0 2 (OH). C ^-CH 2 .CH(NH 2 ) -COOH Tryptophan, Ce is /3-indol a-amino-propionic acid. It is a decom- position product of protein, being produced during tryptic digestion. It, in turn, is attacked by bacteria in the intestines, giving rise to indol. It gives a color reaction with glyoxylic acid (see p. 220). X CO \ Directly related to indol is isatin, CeH 4 <^ ">CO, dioxyindol, for the former can be obtained from the latter by reduction. Indigo, structurally, is a com- bination of two isatin molecules, the end oxygen atom of each molecule being eliminated, thus : Indigo can be produced from isatin. It is a valu- able blue dye. The synthesis of indigo on a com- HETEROCYCLIC COMPOUNDS 419 mercial scale is one of the great achievements of chemistry. Most of the indigo marketed nowadays is artificially produced, the cost of manufacture being only about one-fourth the cost of production of natural indigo. It will be of interest to give an outline of one of the recent commercial methods. Naphthalene is the starting-point of the synthesis. This is oxidized by fuming H 2 S0 4 to phthalic acid, and the latter is converted into phthalimide by the action of ammonia gas; then by treatment with chlorine and caustic soda phthalimide becomes converted into anthranilic acid. This acid is con- densed with monochloracetic acid, COOH giving . Fusion with KOH NH splits off C02 and water, producing XXK CeEU^ /CH, which is then oxidized in alkaline solution to indigo by a current of air. In plants the indigo is contained in a glucoside combination, indican (p. 253). Reduction (adding H) changes indigo to indigo white; it is in this form that it is introduced in alkaline solution into cloth for dyeing; on exposure to air it oxidizes to the insoluble indigo blue. Indigo red, indirubin, is a structural isomer of indigo. EXPERIMENT. Synthesize indigo. To 1 c.c. of water add 3 drops of acetone and a few crystals of orthonitrobenzaldehyde. Warm the mixture in a 420 ORGANIC CHEMISTRY bath kept at 50 for ten minutes. Cool, add a few drops of 10% NaOH and shake. A yellow color appears first, then a green. When it is deep green add chloroform and shake. Indigo dissolves in the chloroform (blue solution). Remove the bottom layer with a pipette, and run it into a sample bottle. As the solvent evaporates indigo is deposited on the wall. CONDENSED PYRIDINE-BENZENE COMPOUNDS Quinoline (chinoline) is another tertiary ammonia base. It may be considered as naphthalene in which a CH group has been replaced by N: ,C 9 H 7 N. CH It is found in coal-tar. When certain alkaloids, particularly quinine and cinchonine, are distilled with potassium hydroxide, quinoline is obtained. Quinoline can be synthesized from aniline and glycerol in the presence of nitrobenzene and concen- trated sulphuric acid (see exp. below): The reac- tions involved are as follows: the glycerol is de- hydrated to acrolein ; removal of a molecule of water from acrolein by further dehydration causes com- bination with aniline forming acrolein-aniline; and finally oxygen from nitrobenzene removes a hydrogen atom from the end of the chain and also HETEROCYCLIC COMPOUNDS 421 from the benzene ring, resulting in the closing of the pyridine ring. CH CH 2 CH CH fCH +0=' +H 2 CH HC UU CH CETN CH N (Acrolein-aniline) (Quinoline) Quinoline is a liquid boiling at 240. By proper treatment of quinoline, pyridine can be derived from it. Many alkaloids are quinoline derivatives. Oxyquinoline Sulphate (chinosol) , (CgHyNO) 2 EbSC^, is a substance used as an antiseptic, and is said to be non-toxic. EXPERIMENT. Synthesize quinoline. " In a liter flask mix 15 gm. of nitrobenzene, 24 gm. of aniline, and 75 gm. of glycerol; add 62 gm. of C.P. H 2 SO 4 while agitating the mixture. Connect with an air- condenser having a diameter of 2 cm., and heat the flask very gradually on a sand-bath. Wrap the condenser with a damp rag. When the reaction begins (sudden bubbling) remove the flame. If the action is very vigorous, cool the upper part of the flask with an air stream from a bellows. When the mixture becomes quiet, heat for three hours on a sand-bath. Then dilute with 300 c.c. of water and distill with steam. When no more oily drops of nitrobenzene come over, stop the distilling. Cool partially, render the mixture alkaline with strong NaOH solution, and again distill with steam, thus 422 ORGANIC CHEMISTRY removing the quinoline and aniline. This last distillate is specially treated to convert the aniline into phenol, as was directed in the experiment under phenol (see p. 338). Diazotize the cooled liquid after rendering it distinctly acid with dilute H 2 S04, warm in a bath, make alkaline (the phenol becomes fixed as a phenolate, while quinoline is set free), and distill with steam. Extract the quinoline from the distillate with ether and proceed just as was done with phenol. Thalline, C 9 H 9 (OCH 3 )NH, and Kairine, C 9 H 9 (OH)N C 2 H 5 , are quinoline de- rivatives that have been used as antipyretics. Analgen (quinalgen) is a more recent antipyretic, C 9 H 5 (OC 2 H 5 )NH(COC6H5)N. Kynurenic acid, occurring in the urine of dogs, is a quinoline derivative, CH COH OH; N it is supposed to be derived from tryptophan. Atophan is one of the newer remedies that is of importance. It is phenyl-quinoline-carboxylic acid, CH C COOH CH N HETEROCYCLIC COMPOUNDS 423 Novatophan is the ethyl ester of methyl atophan. Isoquinoline, CgHyN, is an isomer of quinoline: CH CH CH CH It is of importance because of the derivation of many alkaloids from it. The formula may be written with N at any one of the four positions at the sides of the rings. SYNOPSIS Aromatic Compounds A. BENZENE HYDROCARBONS. Benzene derivatives. 1. Halogen derivatives. 2. Hydroxy derivatives. , ( Ethers. a. Phenols ] _ A , . ., ( Ethereal salts. /i\ AT -j u i (Substitution (1) Monacid phenols < ( products. (2) Diacid phenols. (3) Triacid phenols. 6. Fatty alcohol side-chain compounds and deriva- Alcohols. Aldehydes, tives Ketones. TV/T L -j f Salts. Monobasic acids < _ . / Ethereal salts. c. Phenolic monobasic acids. 3. Dibasic acids. 4. Nitrogen derivatives. (a) Nitro compounds. (6) Amino compounds, (c) Diazo compounds. 424 ORGANIC CHEMISTRY 5. Sulphur derivatives. 6. Arsenic derivatives. 7. Quinones. B. CONDENSED BENZENE RINGS. 1. Naphthalene. 2. Anthracene. 3. Phenanthrene. C. HETEROCYCLIC COMPOUNDS. 1. Pyrrol and pyridine bases. 2. Condensed heterocyclic-benzene rings. (1) Indol and derivatives. (2) Quinoline and derivatives. (3) Isoquinoline and derivatives. D. ALKALOIDS. CHAPTER XXXIII ALKALOIDS AND. DRUG PRINCIPLES ALKALOIDS IN its broadest application the term alkaloid includes all nitrogenous organic substances that are basic in character (alkaloid = alkali-like) . Caffeine and theobromine, purin bases and other leuco- maines, choline, muscarine, and ptomaines have all been called alkaloids. The most recent definition which seems acceptable is that'alkaloids include all nitrogenous plant prod- ucts which have N in a closed chain of atoms. Many of them contain more than one N atom in the molecule. Most alkaloids are tertiary ammonia bases. Those the structure of which is known are derivatives of pyridine, pyrrolidine, quinoline, iso- quinoline, phenanthrene, or purin. The empirical formulae of the chief alkaloids are as follows: Coniine CgHiyN. Nicotine. CioHi 4 N2. Sparteine Ci5H 2 6N2. Theobromine C 7 H 8 N40 2 . Theophylline C 7 H 8 N 4 2 . Caffeine C 8 HioN 4 2 . Pelletierine C 8 H 15 NO. 425 426 ORGANIC CHEMISTRY Pilocarpidine Hydrastinine ...... CnHi 3 NO 3 . Pilocarpine ....... CnHi 6 N 2 2 . Physostigmine ..... Ci5H 2 iN3O2 (Eserine). Eseridine ......... Ci 5 H 23 N 3 O 3 . Homatropine ...... Sinipine .......... Apomorphine ..... Pipeline .......... Ci 7 Hi 9 N0 3 . Morphine Cocaine Hyoscine ......... Ci7H 2 iN04. (Scopolamine). Atropine .......... C 17 H 23 N0 3 . 1 Hyoscyamine ..... Ci7H 23 N03 J Codeine .......... Ci 8 H 2 iNO 3 . Lobeline .......... Ci 8 H 23 N0 2 . Thebaine ......... Ci 9 H 2 iNO 3 . Cinchonine ....... Ci 9 H 22 N 2 1 T r>,. i i- /^ TT AT r\ Isomers. Cmchomdme ...... Ci9H 22 N 2 O Curarine .......... Ci 9 H 26 N 2 O. Sanguinarine ...... Berberine ......... Papaverine ....... Quinine .......... C 20 H 24 N 2 2 (Isomer, Quinidine) Hydrastine ....... C 2 iH 2 iNO6. Strychnine ........ C 2 iH 22 N 2 2 . Narcotine ......... C 22 H 23 N(>7. Colchicine ........ C 22 H 25 NO6. Gelseminine ....... C 22 H 26 N 2 3 . Yohimbine ........ C 22 H 28 N 2 O 3 . Brucine .......... C 23 H 26 N 2 O4. Narceine ALKALOIDS AND DRUG PRINCIPLES 427 Jervine Veratrine Aconitine Ergotinine Ergotoxine Coniine and nicotine are the only important alka- loids that contain no oxygen and that are volatile liquids. Sparteine, pelletierine, and pilocarpidine are liquids, but non-volatile. All of the alkaloids form salts with acids (see p. 258); these salts are very much more soluble in water and alcohol than the free alkaloids. The free alkaloids, on the other hand, are more soluble than their salts in the immis- cible solvents ether, chloroform, benzene, and amyl alcohol. In solution some of the alkaloids are dis- tinctly alkaline. Most of the alkaloids are optically active, and generally Isevorotatory. All alkaloids are precipitated by phosphomolybdic and phosphotungstic acids, most of them by potas- sium mercuric iodide and many of them by tannic acid. Many of the alkaloids are extremely poisonous, but in minute doses they are very valuable remedies. The alkaloids here considered are of vegetable origin. They are present in plants as salts of various organic acids (e.g., citric, malic, and tannic acids). Methods of determining the constitution of alkaloids. By violent reactions (e.g., fusing with alkali, heating with bromine or phosphoric acid, or distilling with zinc dust) the molecule may be shattered, so that as a result of the reaction a 428 ORGANIC CHEMISTRY stable nucleus is found, such as pyridine, quinoline or isoquinoline. Methyl ether Unkings of alkaloids may be broken up by heating with hydriodic acid, and from the methyl iodide formed the number of methoxy groups (OCH 3 ) can be ascertained. Alkaloids that are esters can be hydrolyzed, and the products of hydrolysis can be examined. Hy- droxyl, carboxyl and carbonyl groups are readily determined. In the case of a few alkaloids the struc- ture of the molecule has been proved by synthesis. We shall consider now some of the facts that are known in regard to the structure of alkaloids. PYRIDINE DERIVATIVES It is necessary to designate the positions of groups in the pyridine ring thus: CH( 7 ) \JH(0) (a')HCL JCHfa) Piperidine is the simplest derivative, CH 2 lJcH 2 " H 2 c NH Piperine is contained in pepper. It is a combina tion of piperidine and piperic acid, ALKALOIDS AND DRUG PRINCIPLES 429 Coniine is dextro-^-propyl piperidine, CH 2 H 2 C/NCH 2 H 2 cl JcH CH 2 - CH 2 - CH 3 NH Nicotine is a pyrrol derivative (see p. 414) of pyridine the attachment of methyl pyrrolidine to pyridine being in the position of the latter and position 2 of the former: CH H 2 C CH CH 2 HC CH N CH 3 Coniine and nicotine have marked similarities; both are volatile liquids having a strong odor, and both are very poisonous. Coniine is obtained from hemlock-seed, and nicotine from tobacco. Both are strongly alkaline to litmus. In tobacco the nicotine is combined with malic acid and citric acid. Syn- thetic a-propyl piperidine is identical with coniine, except that it is optically inactive. Optically active coniine can be obtained from this by securing crystals of the tartrate of coniine, the first crop of crystals containing only dextroconiine. This was the first synthesis (1886) of a natural alkaloid. Nicotine is laevorotatory. d Z-Nicotine has been synthesized; from this the I variety is separated by 430 ORGANIC CHEMISTRY crystallization of the tartrate. d-Nicotine is much less toxic than Z-nicotine. Sparteine is thought to be a piperidine derivative, but its chemical structure has not been fully deter- mined. It is dextrorotatory. The artificial alkaloids a- and /3-eucaine are com- plex piperidine bodies. C 6 H 6 COO v c/OOC.CH 3 C 6 H H 2 (X >CH< H 3 & H 3 C CH 3 H (a-eucaine) (3-eucaine) The eucaines are local anaesthetics, and differ from cocaine in action in that they do not affect the pupil. Euphthalmine is related to /3-eucaine, having a CHa group in place of the H attached to N and hav- ing the mandelic acid radicle, CeHs-CHOH-COO instead of the benzoic acid radicle. It dilates the pupil more quickly and less persistently than atropin. It is" not an anaesthetic. PYRROLIDINE DERIVATIVES The alkaloids of the cocaine and atropine group are all pyrrolidine derivatives. This class of alkaloids is of great pharmacological importance. Cocaine is an invaluable local anaesthetic, while members of the atropine group are used to dilate the pupil. The basal substance for all of these compounds is ALKALOIDS AND DRUG PRINCIPLES 431 tropine. This has, as will be noticed, a secondary closed carbon chain: This double ring nucleus is called the tropan nucleus. It may be looked upon as a condensation of the pyrrol with the pyridine ring, hav- ing N and the two neighbor- ing C atoms in common to the two rings. Tropic acid has the formula CH 2 CH CH a C6H - CH W)H ' Atropine is the tropine ester (tropine being an alcohol) of tropic acid, its formula being, HC CH CH, CH CH 2 CH 2 OH 'C 6 H 5 Atropine is optically inactive. Its physiological action is what would be expected of d Z-hyoscyamine. 432 ORGANIC CHEMISTRY Hyoscyamine is laevorotatory. d-Hyoscyamine has a different degree of physiological action. Like other esters, atropine and hyoscyamine can be saponified. Atropine has been synthesized. Atropine and its isomers have a marked pharma- cological action. Eumydrine is the nitrate of methyl atropine, CH 3 and NOs attaching to the N atom of atropine, the latter changing its valence to five. It is used for the same purposes as atropine, but is much less toxic. Homatr opine is an artificial alkaloid prepared by the condensation of tropine and mandelic acid in ester combination. It dilates the pupil more promptly and less persistently than atropine. Scopolamine, also called hyoscine, is an ester, consisting of tropic acid combined with scopolin, C 8 Hi 3 N0 2 , an alcohol derived from pyrrolidine. It is Isevorotatory. It is used to cause analgesia. If in tropine an H atom of a CEb group of the sec- ondary ring be replaced by COOH, ecgonine is obtained : H 2 C| , C H a HC CHOH ALKALOIDS AND DRUG PRINCIPLES 433 From this is derived cocaine, which is the methyl ester of benzoyl ecgonine: H 2 C | 1 C H a HC Cocaine exists both as d and as /, the latter having a more marked action. Cocaine is a very valuable local anaesthetic. Its solution cannot be sterilized by heat, because it hydrolyzes readily, yielding methyl alcohol and benzoylecgonine. Besides this similarity of cocaine to atropine in chemical structure, there are some resemblances in pharmacological action. Tropacocaine has a formula similar to cocaine, but has CH 2 instead of CH-COOCH 3 . It is less toxic than cocaine and as strongly anaesthetic. It has little effect on the pupil. ' Other substitutes for cocaine, namely, novocaine, stovaine, and alypin (see p. 360) have been previously mentioned. Nicotine is a pyrrolidine derivative as well as a pyridine derivative (see p. 429). 434 ORGANIC CHEMISTRY (X)HC QUINOLINE DERIVATIVES The chief alkaloids of this class are the cinchona alkaloids. The following formula has been suggested CH 2 =CH CH CH CH 2 f or cin chonine : Quinine probably has the same for- mula, except that an H atom at the posi- tion marked (X) is replaced by the m e t h o x y group (OCRs). Cinchonine is dex- trorotatory, quinine Isevorotatory. Cin- chonidine is the Isevo- rotatory isomer of cinchonine. Quini- dine is the dextro- rotatory isomer of quinine. Quinine is important as a medicine. It is very bitter. Euquinine, an ester, quinine ethyl carbonate, is tasteless. It gives full quinine action. Aristoquin is similar to euquinine. It is diquinine carbonic ester. Its action is the same as that of quinine, but ifc has none of the disadvantages of the latter. Quinine and urea hydrochloride, a crystalline double salt, is very soluble and is suitable for sub- cutaneous injection, being non-irritating and even anaesthetic locally. N ALKALOIDS AND DRUG PRINCIPLES 435 Strychnine and brucine are believed to be quin- oline derivatives, but their structure has not been fully worked out. Both strychnine and brucine are laevorotatory. Strychnine is much used as a medicine, brucine not at all. ISOQUINOLINE DERIVATIVES The minor opium alkaloids, papaverine, narcotine, and narceine, also hydrastine and berberine, belong to this group. These alkaloids are therapeutically of very little importance (except hydrastine). Papav- erine has the simplest structure; it is tetramethoxy- benzylisoquinoline; its formula is CH 3 CH 436 ORGANIC CHEMISTRY Papaverine has been synthesized. Hydrastine probably has the similar but more com- plicated formula: OCH 3 C H 2 C C\ \/o , CH CH 2 Narcotine is believed to be methoxyhydrastine, the OCHs group taking the place of H at (X). Hydrastinine is an alkaloid prepared by oxida- tion of hydrastine with nitric acid. It has a much stronger physiological, action than hydrastine. Its CH formula is H CH=0 NH CH 3 , CH ALKALOIDS AND DRUG PRINCIPLES 437 the side chain being bent so as to point out its derivation from hydrastine. Narceine has a somewhat similar formula, but it has in addition a benzoic acid group and several methoxy groups. Berberine has a still more complex formula. Cotarnine, C^HisNO^ is an oxidation product of narcotine, as hydrastinine is of hydrastine. Its formula corresponds to the isoquinoline half of the narcotine formula. It is methoxyhydrastinine. Its hydrochloride is called stypticin, and the phthalate is called styptol. Cotarnine and hydrastinine have very similar physiological action; both affect the circulatory system in such a way as to lessen haemorrhage. Cotarnine is much less expensive. PHENANTHRENE DERIVATIVES These are morphine, codeine, and thebaine, all of them being alkaloids present in opium. Derivatives of morphine artificially produced are apomorphine, dionine, heroine and peronine. Morphine is the most valuable alkaloid for thera- peutic purposes that we have. Opium contains about 10% of morphine. Its derivatives are much weaker in physiological action. Its constitutional formula is supposed by some to be: ORGANIC CHEMISTRY HC C-OH (X) Codeine is supposed to have the above formula, with CHs substituted for the H of the OH group at X. Thus codeine is the monomethyl ether of mor- phine. Codeine has been prepared from morphine by treating the latter with methyl iodode in the pres- ence of caustic potash: Ci 7 Hi7NO(OH)2+CH 3 I+KOH = (Morphine) = Ci 7 Hi 7 NO(OH)(OCH 3 ) +KI+H 2 0. (Codeine) ALKALOIDS AND DRUG PRINCIPLES 439 It is prepared by heating a mixture of morphine and potassium methyl sulphate (K(CH 3 )S04) with alcoholic KOH (see exp.). Both morphine and codeine are laevorotatory. Thebaine is supposed to have two less hydrogen atoms attached to the phenanthrene nucleus, and two OCHs groups in place of the two hydroxyls of morphine. By the action of concentrated mineral acids, a molecule of water can be removed from morphine, producing apomorphine: Ci7H 19 N0 3 H 2 O =Ci 7 Hi 7 NO 2 . (Morphine) (Apomorphine) It is supposed that in apomorphine the phenan- threne nucleus is condensed with methyl piperidine. It turns green after long standing. Other derivatives of morphine have been recently put forward as therapeutic agents. Dionine is the hydrochloride of the ethyl ether of morphine, Ci7Hi 7 NO(OH)(OC2H 5 ) -HC1. Heroine is an ester, diacetyl morphine, < Peronine is the hydrochloride of the benzyl ether of morphine Ci 7 Hi7NO(OH)(OCH 2 C 6 H5) -HC1. EXPERIMENTS. (1) Test solutions of morphine sulphate and quinine sulphate with alkaloidal reagents, such as phosphomolybdic acid, picric acid, 440 ORGANIC CHEMISTRY iodine potassium iodide solution, mercuric potassium iodide, and tannic acid solutions. (2) Dissolve quinine in dilute H 2 S04, and notice the fluorescence of the quinine bisulphate solu- tion. (3) Extraction of an alkaloid. To 10 grams of tea add 500 c.c. of water, and heat, keeping the liquid barely at boiling temperature for 15 minutes. Pre- cipitate tannin from the filtrate of this by adding 10% lead acetate, a drop at a time, until no more precipitate forms. Filter, and evaporate to about 75 c.c. Cool the solution, and if it is turbid filter again. Extract it twice by shaking with two por- tions of 15 c.c. of chloroform. Dry the chloroform with anhydrous Na2S(>4. Filter through a small filter into an evaporating dish. Let the chloroform evaporate spontaneously, then examine the crystal- line character of the caffeine residue. Remove a little of it, and taste it. Dissolve part of the residue in a few c.c. of hot water and test the solution with alkaloidal reagents (exp. 1). (4) Produce codeine. Dissolve 1 gm. of morphine (pure alkaloid) and 0.6 gm. potassium methyl sul- phate in 50 c.c. of pure methyl alcohol, warming and shaking. Then add an excess of powdered KOH until strongly alkaline, attach a reflux condenser and heat in a water-bath for two hours. Add 20 c.c. of water, neutralize with HC1 and distill off all volatile materials on a boiling water-bath. Cool, make slightly alkaline with ammonia and filter; transfer to a separating funnel, and shake with sev- eral portions of benzene. Dry the combined ben- ALKALOIDS AND DRUG PRINCIPLES 441 zene extracts with calcium chloride, filter into an evaporating dish, and evaporate to dryness on a water-bath. Dissolve part of the residue with 2% HC1, warming gently. Test a drop of the solution with potassium mer- curic iodide solution. Also make the following test: (a) make a paste of some ammonium molyb- date with a few drops of C.P. H 2 SO 4 ; on adding a drop of the alkaloid solution a blue color is obtained, warm if necessary to develop the color; (6) to a few drops of the solution add 2 c.c. of H 2 S0 4 containing 1 drop of formaline, and a reddish-violet color ap- pears. These two tests are given also by morphine, but morphine cannot be extracted by means of benzene. A test given by codeine, but not by mor- phine, is this: to the residue in the evaporating dish add about 1 c.c. of 20% H 2 S0 4 and warm, a faint pink color appears. This method of synthesis should yield considerable impure codeine. Crystals can be obtained by dis- solving a little in chloroform, and allowing a drop of the solution to evaporate on a slide. PURIN DERIVATIVES The methyl xanthins, caffeine and theobromine, have been discussed elsewhere (p. 293). Theophylline is 1, 3- dimethyl- 2, 6- dioxypurin, an isomer, therefore, of theobromine. These three alkaloids can be prepared synthetically. All are used as remedies. Pilocarpine does not have the full purin nucleus, but has the heterocyclic ring imidazol (see p. 414). 442 ORGANIC CHEMISTRY C 2 H 5 CH CH - CH 2 I I I OC CH 2 C N^- V II O HC W It is dextrorotatory. It has a marked pharmaco- logical action. CERTAIN ALKALOIDS THAT HAVE NOT BEEN CLASSIFIED The following indicates what is known about the structure of aconitine : OC-CH 3 C 21 H 2 ,(OCH 3 )4(N0 5 ) Colchicine is given the formula: -COOCH 3 DRUG PRINCIPLES OF UNKNOWN STRUCTURE Cantharidin, CioHi 2 O4, is an acid lactone, derived from either benzene or cyclohexane. Picrotoxin, CisHieOe. Picropodophyllin, C 23 H 24 9 2H 2 0. APPENDIX Note to the Instructor. 1 If it is desired to shorten the time given to the experiments, we should advise omitting the following: preparation of phenol from potassium benzene sulphonate (see p. 392), the diazonium experiments (see p. 386), preparation of sulphanilic acid (see p. 395), of quinoline (see p. 421), and of codeine (see p. 440). Diazonium salt may be prepared as a demon- stration by the instructor. To permit of using one apparatus (as a Beckmann apparatus or a combustion furnace) with the entire class, we should suggest dividing the class or a section of it into five groups of three or four men each, the men of each group working together on a particular experiment, but the various groups performing different experiments on the same day. Thus, one group may do crystallization and melting-point experiments (see pp. 9, 10), a second may carry out fractional distillation (see p. 14) and boiling- point determination (see p. 18), a third may make *We can recommend as valuable books for reference the textbooks of organic chemistry by Holleman, W. A. Noyes, Bernthsen, and Meyer and Jacobson, the laboratory manuals by Gattermann (translated by Schober), W. A. Noyes, and Cohen, and " Introduction to Physical Chemistry," by Walker. 443 444 APPENDIX specific gravity determinations (see p. 25), a fourth may do a combustion analysis (see p. 32), and a fifth may use the Beckmann apparatus (see p. 62). Each group will, of course, have to take the experi- ments in a different order, thus : Group I, Lessons 1, 2, 3, 4, 5. Group II, Lessons 2, 3, 4, 5, 1. Group III, Lessons 3, 4, 5, 1, 2. Group IV, Lessons 4, 5, 1, 2, 3. Group V, Lessons 5, 1, 2, 3, 4. Spellings. We have retained the ending " ine " in the case of amines and alkaloids, with the idea of indicating by this means the organic substances that are distinctly basic in character. Formulce. We strongly advise that the learning of empirical formulae by the student be discouraged, but that, on the other hand, the student be thoroughly drilled in giving structural formulae. The Student. Many students need advice as to the proper method of studying chemistry, since some try to learn it by rote. Medical students should be urged to retain this textbook for use as a reference book while studying biochemistry, physiology, path- ology, and pharmacology. REFERENCE TABLES TABLE I SPECIFIC GRAVITY AND PERCENTAGE OF ALCOHOL [According to Squibb.] Per Cent Alcohol by Volume. Per Cent Alcohol by Weight. SPECIFIC GRAVITY. Per Cent Alcohol by Volume. Per Cent Alcohol by Weight. SPECIFIC GRAVITY. At 15.56 At 25 15.56 At 15.56 15.56 At 25 15.56 U 15.56^ 1 0.79 0.9985 0.9970 31 25.51 0.9643 0.9594 2 1.59 .9970 .9953 32 26.37 .9631 .9582 3 2.39 .9956 .9938 33 27.23 .9618 .9567 4 3.20 .9942 .9922 34 28.09 .9609 .9556 5 4.00 .9930 .9909 35 28.96 .9593 .9538 6 4.80 .9914 .9893 36 29.83 .9578 .9521 7 5.61 .9898 .9876 37 30.70 .9565 .9507 8 6.42 .9890 .9868 38 31.58 .9550 .9489 9 7.23 .9878 .9855 39 32.46 .9535 .9473 10 8.04 .9869 .9846 40 33.35 .9519 .9456 11 8.86 .9855 .9831 41 34.24 .9503 .9438 12 9.67 .9841 .9816 42 35.13 .9490 .9424 13 10.49 .9828 .9801 43 36.03 .9470 .9402 14 11.31 .9821 .9793 44 36.93 .9452 .9382 15 12.13 .9815 .9787 45 37.84 .9434 .9363 16 12.95 .9802 .9773 46 38.75 .9416 .9343 17 13.78 .9789 .9759 47 39.67 .9396 .9323 18 14.60 .9778 .9746 48 40.60 .9381 .9307 19 15.43 .9766 .9733 49 41.52 .9362 .9288 20 16.26 .9760 .9726 50 42.52 .9343 .9267 21 17.09 .9753 .9719 51 43.47 .9323 .9246 22 17.92 .9741 .9706 52 44.42 .9303 .9226 23 18.76 .9728 .9692 53 45.36 .9283 .9205 24 19.59 .9716 .9678 54 46.32 .9262 .9184 25 20.43 .9709 .9668 55 47.29 .9242 .9164 26 21.27 .9698 .9655 56 48.26 .9221 .9143 27 22.11 .9691 .9646 57 49.23 .9200 .9122 28 22.96 .9678 .9631 58 50.21 .9178 .9100 29 23.81 .9665 .9617 59 51.20 .9160 .9081 30 24.66 .9652 .9603 60 52.20 .9135 .9056 445 446 REFERENCE TABLES TABLE I Continued [According to Squibb.] Per Cent Alcohol by Volume. Per Cent Alcohol by Weight. SPECIFIC GRAVITY. Per Cent Alcohol by Volume. Per Cent Alcohol by Weight. SPECIFIC GRAVITY. At 15.56 15.56 At 25 15.56 ' At 15.56 15.56 At 25 15.56 61 53.20 0.9113 0.9034 81 74.74 0.8611 0.8530 62 54.21 .9090 .9011 82 75.91 .8581 .8500 63 55.21 .9069 .8989 83 77.09 .8557 .8476 64 56.22 .9047 .8969 84 78.29 .8526 .8444 65 57.20 .9025 .8947 85 79.50 .8496 .8414 66 58.27 .9001 .8923 86 80.71 .8466 .8384 67 59.32 .8973 .8895 87 81.94 .8434 .8352 68 60.38 .8949 .8870 88 83.19 .8408 .8326 69 61.42 .8925 .8846 89 84.46 .8373 .8291 70 62.50 .8900 .8821 90 85.75 .8340 .8258 71 63.58 .8875 .8796 91 87.00 .8305 .8223 72 64.66 .8850 .8771 92 88.37 .8272 .8191 73 65.74 .8825 .8746 93 89.71 .8237 .8156 74 66.83 .8799 .8719 94 91.07 .8199 .8118 75 67.93 .8769 .8689 95 92.46 .8164 .8083 76 69.05 .8745 .8665 96 93.89 .8125 .8044 77 70.18 .8721 .8641 97 95.34 .8084 .8003 78 71.31 .8696 .8616 98 96.84 .8041 .7960 79 72.45 .8664 .8583 99 98.39 .7995 .7914 80 73.59 .8639 .8558 100 100.00 .7946 .7865 The table of the U. S. Bureau of Standards gives specific gravities for a number of concentrations of alcohol differing from those in this table by 0.0002 to 0.0005; for instance, the figures for 95-100% alcohol are lower by 0.0004-0.0006. REFERENCE TABLES 447 TABLE II MILLIGRAMS OF PURE NITROGEN IN 1 c.c. OF THE MOIST GAS AT VARIOUS TEMPERATURES AND UNDER VARIOUS PRESSURES (MILLIMETERS OF MERCURY) Tem- perature. 721 724 727 730 733 736 739 742 10 1.130 1.135 1.139 1.144 .149 1.154 .158 .163 11 .125 1.129 1.134 1.139 .144 1.148 .153 .158 12 .120 1.124 1.129 1.134 .139 1.143 .148 .153 13 .115 1.119 1.124 1.129 .134 1.138 .143 .148 14 .110 1.114 1.119 1.124 .129 1.133 .138 .143 15 .105 1.109 1.114 1.119 .124 1.128 .133 .138 16 .099 1.103 1.108 1.113 .118 1.123 .127 .132 17 .094 1.098 1.103 1.108 .113 1.118 .122 .127 18 .089 1.093 1.098 1.102 .107 1.112 .116 .121 19 .084 1.088 1.093 1.097 .102 1.107 .111 1.116 20 .079 1.083 1.088 1.092 .097 1.102 .106 1.111 21 .074 1.078 1.082 1.087 .091 1.096 .101 1.106 22 .068 1.072 1.076 1.081 .086 1.091 .095 1.100 23 .062 1.067 1.071 1.076 .080 1.085 .090 1.094 24 .057 1.061 1.066 1.071 .075 1.080 .084 1.089 25 .051 1.056 1.060 .065 .069 1.074 .078 1.083 26 .046 1.050 1.054 .059 .064 1.068 .072 1.077 27 .040 1.044 1.048 .053 .058 1.062 .066 1.071 28 .034 1.038 1.042 .047 .052 1.0C3 .060 1.065 29 .028 1.032 1.036 .041 .046 1.050 .054 1.059 30 .022 1.026 1.031 .035 .040 1.044 .048 1.053 Tem- perature. 745 748 751 754 757 760 763 766 10 1.168 1.173 .177 .182 1.187 1.192 .197 1.202 11 1.162 1.167 .172 .176 1.181 1.186 .191 1.196 12 1.157 1.162 .167 .171 1.176 1.181 .186 .190 13 1.152 1.157 .162 .166 1.171 1.176 .181 .185 14 1.147 1.152 .157 .161 1.166 1.171 .176 .180 15 1.142 1.147 .152 .156 1.161 1.166 .170 .175 16 1.137 1.141 .146 .150 1.155 1.160 .164 .169 17 1.131 1.136 .140 .144 1.149 1.154 .158 .163 18 1.125 1.130 .135 .139 1.144 1.149 .153 .158 19 1.120 1.125 .130 .134 1.139 1.144 .148 .153 20 1.115 1.120 .125 .129 1.134 1.138 .143 .148 21 1.110 1.114 .119 .123 1.128 1.133 .138 .142 22 1.104 1.108 1.113 .117 1.122 1.127 .132 .136 23 1.098 1.103 1.107 .111 1.116 1.121 .126 .131 24 1.093 1.097 1.101 .106 1.111 1.116 1.121 .125 25 1.087 1.092 1.096 .101 1.105 1.110 1.115 .119 26 1.082 1.086 1.090 .095 1.099 1.104 1.108 .113 27 1.076 1.080 1.084 .089 1.093 1.098 1.102 .107 28 1.070 1.074 1.078 .083 1.087 1.092 1.096 .101 29 1.063 1.068 1.072 1.077 1.081 1.086 1.090 .095 30 1.057 1.062 1.066 1.071 1.075 1.080 1.084 .089 448 REFERENCE TABLES TABLE III SPECIFIC GRAVITY AND PERCENTAGE OF NaOH IN AQUEOUS SOLUTION Specific Gravity at 15. Per Cent NaOH. Gm. NaOH in 100 c.c. Specific Gravity at 15. Per Cent NaOH. Gm. NaOH in 100 c.c. 1.007 0.61 0.6 1.220 19.58 23.9 1.014 1.20 1.2 1.231 20.59 25.3 1.022 2.00 2.1 1.241 21.42 26.6 1.029 2.71 2.8 1.252 22.64 28.3 .036 3.35 3.5 .263 23.67 29.9 .045 4.00 4.2 .274 24.81 31.6 .052 4.64 4.9 .285 25.80 33.2 .060 5.29 5.6 .297 26.83 34.8 .067 5.87 6.3 . .308 27.80 36.4 1.075 6.55 7.0 .320 28.83 38.1 1.083 7.31 7.9 .332 29.93 39.9 1.091 8.00 8.7 . .345 31.22 42.0 1.100 8.68 9.5 .357 32.47 44.1 1.108 9.42 10.4 1.370 33.69 46.2 1.116 10.06 11.2 1.384 34.96 48.3 1.125 10.97 12.3 1.397 36.25 50.6 1.134 11.84 13.4 .410 37.47 52.8 1.142 12.64 14.4 .424 38.80 55.3 1.152 13.55 15.6 .438 39.99 57.5 1.162 14.37 16.7 .453 41.41 60.2 1.171 15.13 17.7 .468 42.83 62.9 1.180 15.91 18.8 .483 44.38 65.8 1.190 16.77 20.0 .498 46.15 69.1 1.200 17.67 21.2 1.514 47.60 ' 72.1 1.210 18.58 22.5 1.530 49.02 75.0 REFERENCE TABLES 449 TABLE IV SPECIFIC GRAVITY AND PERCENTAGE OF KOH IN AQUEOUS SOLUTION Specific Gravity at 15. Per Cent KOH. Gm. KOH in 100 c.c. Specific Gravity at 15. Per Cent. KOH. Gm. KOH in 100 c.c. 1.007 0.9 0.9 1.252 27.0 33.8 1.014 1.7 1.7 1.263 28.0 35.3 1.022 2.6 2.6 1.274 28.9 36.8 1.029 3.5 3.6 1.285 29.8 38.5 1.037 4.5 4.6 1.297 30.7 39.8 .045 5.6 5.8 1.308 31.8 41.6 .052 6.4 6.7 1.320 32.7 43.2 .06fr 7.4 7.8 1.332 33.7 44.9 .067 8.2 8.8 1.345 34.9 46.9 .075 9.2 9.9 1.357 35.9 48.7 .083 10.1 10.9 1.370 36.9 50.6 .091 10.9 11.9 1.383 37.8 52.2 .100 12.0 13.2 1.397 38.9 54.3 .108 12.9 14.3 1.410 39.9 56.3 .116 13.8 15.3 1.424 40.9 58.2 .125 14.8 16.7 1.438 42.1 60.5 .134 15.7 17.8 1.453 43.4 63.1 142 16.5 18.8 1 ,468 44.6 65.5 .152 17.6 20.3 1.483 45.8 67.9 1.162 18.6 21.6 1.498 47.1 70.6 1.171 19.5 22.8 1.514 48.3 73.1 1.180 20.5 24.2 1.530 49.4 75.6 1.190 21.4 25.5 . 1.546 50.6 77.9 1.200 22.4 26.9 1.563 51.9 81.1 1.210 23.3 28.2 1.580 53.2 84.0 1.220 24.2 29.5 1.597 54.5 87.0 1.231 25.1 30.9 1.615 55.9 90.2 1.241 26.1 32.4 1.634 57.5 94.0 450 REFERENCE TABLES TABLE V ACETIC ACID SPECIFIC GRAVITY AT 15 OP VARIOUS CONCENTRATIONS. FREEZING-POINT, AS AFFECTED BY WATER-CONTENT. Per Cent of Acetic Acid. Specific Gravity. Per Cent of Acetic Acid. Specific Gravity. Per Cent of Water. Freez- ing- point. Per Cent of Water. Freez- ing- point. 10.0 1.014 60.0 1.069 1.0 14.8 5.6 8.2 20.0 1.028 70.0 1.073 2.0 13.25 6.5 7.1 30.0 1.041 80.0 1.075 2.9 11.95 8.3 5.3 40.0 1.052 90.0 1.071 3.8 10.5 9.1 4.3 50.0 1.062 100.0 1.055 4.8 9.4 9.9 3.6 TABLE VI VAPOR TENSION (AQUEOUS PRESSURE IN MILLIMETERS OF MER- CURY) OF WATER AND OF 40% KOH AT VARIOUS TEMPERA- TURES. Tem- pera- ture. Pure HtO. 40% KOH. Tem- pera- ture. Pure H 2 0. 40% KOH. Tem- pera- ture. Pure H 2 0. 40% KOH. 4.6 2.6 12 10.5 5.8 24 22.2 11.7 1 4.9 2.8 13 11.2 6.1 25 23.5 12.4 2 5.3 3.0 14 11.9 6.5 26 25.0 13.1 3 5'.7 3.2 15 12.7 6.9 27 26.5 13.8 4 6.1 3.4 16 13.6 7.4 28 28.1 14.7 5 6.5 3.6 17 14.4 7.8 29 29.8 15.5 6 7.0 3.9 18 15.4 8.3 30 31.6 16.4 7 7.5 4.1 19 16.4 8.9 31 33.4 17.3 8 8.0 4.4 20 17.4 9.3 32 35.4 18.3 9 8.6 4.7 21 18.5 9.9 33 37.4 19.4 10 9.2 5.1 22 19.7 10.5 34 39.6 20.5 11 9.8 5.4 23 20.9 11.1 35 41.9 21.5 REFERENCE TABLES 451 TABLE VII THE DISSOCIATION CONSTANTS OF CERTAIN ORGANIC ACIDS Substance. lOOtf. Substance. 10QK. Formic. 02140 /3-Hydroxypropionic 00311 Acetic 0.00180 Lactic 0138 Propionic. 00145 Glyceric 0228 Butyric 00175 Malonic . . . 163 Valerianic 0.00156 Succinic 00665 Caproic 00147 Glutaric 00475 Monochloracetic. 155 Tartaric 097 Dichloracetic 5 144 Benzoic 006 Trichloracetic. . . . Monobromacetic 120.00 138 o-Hydroxybenzoic, salicylic 102 Cyanacetic Glycollic Oxalic. 0.370 0.0152 10 06 ra-Hydroxybenzoic . . p-Hydroxybenzoic . . Phenol 0.0087 0.0029 000000013 TABLE VIII DISSOCIATION CONSTANTS OF CERTAIN BASES Substance. IOOK. Substance. WOK. Ammonia 0.0023 Diethylamine . . . 126 Methylamine . 050 Trimethylamine 0074 Ethylamine. 0.056 Triethylamine 064 Dimethylamine . . . . 0.074 Benzylamine 0024 452 REFERENCE TABLES TABLE IX THE POWER OF CERTAIN ACIDS TO CAUSE HYDROLYSIS Acid. Inversion Coefficients (Cane- sugar) . Velocity Coefficients (Methylace- tate). Velocity Coefficients (Acetamide). Hydrochloric acid 1 000 1 000 1 000 Nitric acid 1 000 915 955 Hydrobromic 1 114 983 972 Sulphuric acid 0.536 541 547 Formic acid 0153 0131 00532 Acetic acid 0040 00345 000747 Monochloracetic acid 0484 0430 0295 Dichloracetic acid 271 2304 245 Trichloracetic acid. ' 754 6820 670 Oxalic acid 1857 1746 169 Succinic acid. 00545 00496 00195 Citric acid 0172 01635 00797 INDEX Absolute alcohol, 142 Acetaldehyde, 151 Acetaldehyde cyanhydrin, 147 Acetamide, 274 Acetaminophenetole, 382 Acetanilide, 381 Acetates, 165 Acetic acid, 161 ' ' , freezing-point ta- ble, 450 " , glacial, 163 " ' ' metallic salts, 165 " " , mol. wt. determi- nation, by silver salt, 40 " " , proofs of structural formula, 164 " " , specific gravity ta- ble, 450 " > " tests, 163 Acetic anhydride, 169, 206 Acetic ether, 179 Aceto-acetic acid, 192, 218 Acetone, 190 Acetonitrile, 256 Acetophenone, 355 Acetozone, 352 Acetphenetidin, 382 Acetylation, 169, 206 Acetyl chloride, 166 Acetylene, 304 Acetylenes, 304 Acetyl group, 166 ' ' paraminophenyl salicy- late, 367 ' ' salicylic acid, 367 Acetyl value, 206 Achroodextrin, 250 Acid amides, 115, 273 " chlorides, 166 " imides, 284 " strength, estimation of, 183, 184 " value, 205 Acids, 113 " , aromatic, 356 ' ' , dibasic aromatic, 371 11 , fatty, 157 " , H ion concentration of, 405 ' ' , monobsic aromatic, 356 " , monobasic, dibasic, etc., 113 " , strength of, 172 Aconitine, 427, 442 Acrolem, 302 Acrylic acid, 302 Acrylic aldehyde, 302 Acyclic compounds, 116 Acyl halogenides, 166 Adenin, 293 Adrenalin, 383 Adsorption, 95, 209, 407 Agar-agar, 251 Agaric acid, 222 Agaricinic acid, 222 Airol, 370 Alanin, 268 Alcohol, absolute, 142 ' ' , denatured or methylat- ed, 142 ' ' , heat of combustion, 137 453 454 INDEX Alcohol, ordinary, 141 " , specific gravity tables, 445 Alcohols, 109 ' ' , aromatic, 349 " , diacid, 193 ** , monacid, diacid, etc., 112 ' ' , monacid primary, 138 " , oxidation products of, 112 " , primary, 110, 136 11 , secondary, 110, 189 " , tertiary, 110, 192 " , triacid, 199 Aldehyde, 151 acid, 219, 221 1 ammonia, 147 ' bisulphite, 147 ' group, 113 tests, 147, 153 Aldehydes, 112, 146 " , aromatic, 349 Aldohexose, 231 Aldol, 151 Aldol condensation, 151 Aldose, 228, 231 Aliphatic division of organic chemistry, 103 Alizarin, 412 Alkaloidal precipitants, 427 Alkaloid, extraction of, 440 Alkaloids, 425 , determination of chemical structure of, 427 Alkyl cyanides, 256 " hydroxides, 136 " halides, 124 Alkyls, 108 Allantoin, 292 Alloxan, 287 Alloxuric bodies, 293 Allyl alcohol, 302 ' ' isothiocyanate, 307 " radicle, 302 Allyl sulphide, 307 " sulphocarbamide, 308 " thiourea, 308 Aloin, 412 Alpha naphthol, 409 Alpha naphthylamine, 410 Alphozone, 198 Alypin, 360 Amicrons, 87 Amido acids, 266 Amido group, 114 Amines, 258 Amines, mixed aromatic fatty, 379 Aminoacetic acid, 268 Aminoacetphenetidin, 383 Amino acids, 114, 234, 266 Aminoazobenzene, 387 Aminobenzoic acids, 360 Amino compounds, aromatic, 376 !3-Aminoethysulphonic acid, 272 Aminoformic acid, 266 a-Aminoglutaric acid, 269 Aminohexose, 233 a-Aminoisobutylacetic acid, 269 Aminophenols, 382 a-Aminopropionic acid, 268 Aminosuccinic acid, 269 Aminoiso valeric acid, 269 Ammonia derivatives, 114 Ammonium carbamate, 266 Ammonium cyanate, 278 Amphoteric electrolytes, 267 Amphoteric reaction, 403 Amygdalin, 252, 351 Amyl alcohol, fermentation, 144 " '" , inactive, 145 " " , normal, 144 Amylene hydrate, 145 Amyl nitrite, 265 Amylodextrin, 250 Amylopectinj 250 Amyloid, ^246 Amylose, 250 Amylum, 249 Amyl valerate, 187 INDEX 455 Ansesthesin, 367 Anaesthetics, 125, 128, 133 Analgen, 422 Analysis, elementary, 28 Anhydrides, 169, 198, 371 Anhydrolysis, 255 Anilides, 381 Aniline, 376 ' ' derivatives of, 378 " salts, 377 Anions, 66 Anisole, 340 Anozol, 131 Anthracene, 411 Anthracene oil, 318 Anthranilic acid, 383 Anthraquinone, 412 Antifebrine, 381 Antikamnia, 381 Antinosin, 372 Antipyretics, 381, 415 Antipyrin, 415 Antipyrin mandelate, 415 Apiol, 347 Apomorphine, 439 Aqueous pressure, 450 Arabinose, 229 Arachidic acid, 187 Arbutin, 252 Arginase, 270 Arginin, 270 Aristol, 131, 344 Aristoquin, 434 Aromatic acids, 356 ' ' alcohols, 349 " amines, 376 " bases having nitrogen in nucleus, 414 " compounds, 103, 116, 316 1 ' compounds, having condensed rings, 409 Aromatic compounds, synopsis of, 423 reactions of, 317 Aromatic hydroxy compounds, 336 ketones, 354 ' ' nitrogen derivatives, 374 ' ' sulphur derivatives, 391 Arsacetin, 397 Arsanilic acid, 397 Arseno-benzol, 396 Arsine, substitution derivatives of, 264 Aseptol, 393 Asparagin. 277 Asparaginic acid, 269 Aspartic acid, 269 Aspirin, 367 Association of liquids, 69 " " molecules of so- lute, 69 Asymmetric N atom, 216 Asymmetric carbon atom, 216 Atomic weight of elements in organic compounds, 2 Atophan, 422 Atoxyl, 397 Atropine, 431 Autocatalysis, 219 Auxochromes, 407 Avogadro's hypothesis, 42 Azobenzene, 388 Baeyer's reagent, 301 Baking powder, 224 Ballistite, 201 Balsams^SS Balsam of Peru, 358 " ofTolu, 358 Barfoed's reagent, 241 Barometer, correction for tem- perature, 20 Bases, strength of, 172 Bassorin, 251 Beckmann's thermometer, 60 Beer, see Malt liquors. Beet sugar, 243 Behenic acid, 187 456 INDEX Benzal chloride, 351 Benzaldehyde, 351 Benzamide, 361 Benzanilide, 382 Benzene, 318 derivatives, 116, 316 " diazonium nitrate, 384 ' ' diazonium sulphonic acid, 395 " , di substitution prod- ucts of, 326 " , homologues of, 329 model, Collie's, 324 ' ' , preparation of, 320 ring,. 323 " , structure of, 320 " sulphonic acid, 392 " trisubstitution deriva- tives, 328 Benzeugenol, 347 Benzidine, 388 Benzine, 121 Benzoates, 358 Benzoic acid, 330, 356, 386 ' ' " , preparation of, 358 " " ', salts of , 358 " " , substitution prod- ucts of, 359 Benzoic aldehyde, 351 Benzoin, 352 Benzol, 318 Benzonitrile, 386 Benzophenone, 354 Benzoquinone, 398 Benzosol, 345 Benzosulphinide, 394 Benzotrichloride, 357 Benzoylacetyl peroxide, 352 Benzoylaminoacetic acid, 360 Benzoyl anilide, 382 Benzoyl chloride, 359 Benzoylation, 359 Benzozone, 352 Benzyl acetate, 350 Benzyl alcohol, 349 Benzyl chloride, 334 Benzyl methyl ether, 350 Berberine, 437 Betaine, 261 Beta naphthol, 409 Beta naphthylamine, 410 Betol, 368 Bicyclic compounds, 310 Biological methods for test- ing molecular concentration, 54 Bitter almonds, oil of, 351 Biuret, 280 Biuret reaction, 280, 296 Bleier and Kohn, vapor den- sity determination, 44 Blood, depression of freezing- point, 64 Boiling-point determination, 18 at 760 mm., 19 Borneol, 313 Boyle's law, 41 Branched chains, 105, 123 Brandy, 140 Bromobenzene, 333 Brometone, 192 Bromoform, 129 Bromural, 283 Brownian motion, 88 Brucine, 435 Butane, 105, 120 Butter, 203, 204 Butyl alcohol, normal, 144 Butyl chloral hydrate, 156 Butyric acid, 185 Butyrin, 186, 200, 203 Butyrolactone, 219 Cacodylic acid, 264 Cadaverine, 263 Caffeine, 294, 441 Camphor, 312 " , artificial, 311 " monobromide, 313 , oil, 347 Camphoric acid, 313 Cane sugar, 241, 243 INDEX 457 Cantharidin, 442 Caoutchouc, 314 Capillarity, 73 Capri c acid, 187 Caprin, 203 Caproic acid, 187 Caproin, 203 Caprylic acid, 187 Caprylin, 203 Caramel, 244 Caraway, oil of, 344 Carbamic acid, 266 Carbamide, 277 Carbinol, 138 Carbohydrates, 227 Carbolic acid, 337 Carbolic oil, 318 Carbon atom, asymmetric, 216 * ' , detection of, 3 ' ' , estimation of, 28 oxychloride, 128 11 tetrachloride, 120 Carbonyl group, 113 Carboxyl group, 113 Carboxylic acids, 157 Carnitine, 262 Carvacrol, 313, 343 Castor oil, 204, 304 ' Catalytic action, 161, 179, 240, 249 Catalysis, 179 Cataphoresis, 91 Catechol, 345 Cathode, 66 Cations, 66 Celloidin, 248 Celluloid, 248 Cellulose, 246 Cellulose nitrates, 247 esters, 247 Centric benzene formula, 323 Cephalin, 262 Ceryl alcohol, 192 Cetyl alcohol, 192 Cetyl palmitate, 192 Chemical equilibrium, 175 Chemical structure, how deter- mined, 6 Chinoline, 420 Chinosol, 421 Chloracetic acids, 170 Chloral, 154 Chloral alcoholate, 154 Chloralamide, 156 Chloral formamide, 156 Chloral hydrate, 154 Chloralose, 156 Chloral substitutes, 156 Chlorbenzene, 333, 385 Chlorbenzoic acids, 334, 360 Chlorbenzyl alcohol, 350 Chloretone, 191 Chlorhydrins, 200 Chlorine, detection of, 5 Chloroform, 127 11 acetone, 191 " , as reducing agent, 238 11 , molecular weight determination, 44 Chlorpropionic acids, 185 Chlortoluenes, 334 Cholalic acid, 220 Cholesterine, 315 Cholesterol, 315 Cholic acid, 220 Choline, 261 Chromophore group, 406 Chrysarobin, 413 Chrysophanic acid, 413 Cinchonidine, 434 Cinchonine, 420, 434 Cineol, 314 Cinnamic acid, 362 Cinnamic aldehyde, 353 Cinnamon oil, 354 Citrates, 226 Citric acid, 226 Closed carbon chains, 309 Cloves, oil of, 347 Coal gas, 119 Cocaine, 433 458 INDEX Codeine, 438 Cod liver oil, 204 Coefficient of dissociation, 68 Colchicine, 442 Collargol, 97 Collie's benzene model, 324 Collodion, 248 Colloidal solutions, 79, 210, 407 Colloids, 79, 210, 249, 407 ' , irreversible, 83 ' , precipitation of, 92 1 , protective, 96 ' , reversible, 84 , swelling of, 97, 211 Combustion analysis, 28 analysis, modified when halogens present, 36 analysis, modified when nitrogen present, 35 analysis, modified when sulphur present, 36 " furnace, 30 Condensation, 231, 234 Condensed benzene rings, 409 Conductivity, electrical, 65 Conglomerates, 216 Congo red, 402. 410 Coniine, 429 Constants, 60 Constitutional formula, see Structural. Copper acetate, 166 Copper acetylide, 305 Copper-zinc couple, 118 Cordite, 201 Cotarnine, 437 Cream of tartar, 224 Creatin, 285 Creatinin, 285 Creolin, 343 Creosols, 346 Creosote, 346 Creosote oil, 318 Cresols, 343 Cresylic acid, 343 Croton chloral, 156 Crotonic acid, 303 Croton oil, 204 Crystallization, 7 Cryoscopy, 59 Crystals, purity of, 10 Cyanacetic acid, 257 Cyan acids, 257 Cyanamide, 278 Cyanic acid, 257, 278 Cyanides, 114, 256 " , aromatic, 393 Cyanpropionic acids, 197 Cyclic compounds, 309 Cyclopentane, 309 Cyclopropane, 309 Cy close, 310 Cymene, 310, 332 Cymogene, 121 Cystein, 272 Cystin, 272 Cytosin, 295 Dalton's law, 41 Definition of organic chemis- try, 1 Denatured alcohol, 142 Depression of freezing-point by solutions, 59 Dermatol, 370 Destructive distillation, 162 Developers, photographic, 345 Dextrin, 141, 249, 260 Dextroconiine, 429 Dextrolactic acid, 217 Dextrose, 231, 238 Diabetes, 238 Diacid phenols, 345 Dialkyl sulphides, 306 Dialuric acid, 290 Dialysis, 22, 85 Diamino - dihydroxy - diarseno (di) benzene, 396 Dianthracene, 411 INDEX 459 Diastase, 141 Diazoaminobenzene, 387 Diazoamino compounds, 387 Diazo compounds, 384 Diazonium salts, 384 Diazotizing, 338 Dibasic aromatic acids, 371 . Dibrommethane, 127 Dichloracetic acid, 170 Dichlorhydrin, 200 Dichlormethane, 127 Diethyl oxalate, 273 Diffusion of colloids, 85 Digitalin, 253 Digitalose, 230, 253 Digitonin, 253 Digitoxin, 253 Digitoxose, 230, 253 Diglyceride, 207 Dihydroxy ace tone, 228 Dihydroxyanthraquinone, 412 Dihydroxybenzoic acid, 368 Dihydroxydibasic acids, 222 Dihydroxy monobasic acids, 219 Dhydroxyphenylacetic acid, 371 Dihydroxy toluene, 347 Dihydroxystearic acid, 207 Diiodoform, 131 Diiodomethane, 127 Diiodomethyl salicylate, 366 Diketones, 398 Dimethylamine, 261 Dime thy laminoazobenzene, 387, 402 Dimethylaminoazobenzene-sul- phonic acid, 395 Dimethylaniline, 380 Dimethyl xanthin, 293 Dinitrobenzene, 375 Dionine, 439 Dioses, 228 Dioxyindol, 418 Dipalmito-olein, 204 " stearin, 204 Dipeptides, 297 Diphenylamine, 380 Diphenylaminoazobenzene-sul- phonic acid, 396 Diphenylketone, 354 Disaccharides, 228, 240 Dissociation, coefficient of, 68 Dissociation constants of acids, 451 " " of bases, 451 , electrolytic, 65 , hydrolytic, 70, 209 Distil ation, destructive, 162 , fractional, 13 , steam, 16 , vacuum, 16 Disuccinyl peroxide, 198 Dithymol diiodide, 344 Dormiol, 156 Drug principles, 442 Dulcitol, 232 Dumas, vapor density deter- mination, 43 Duotal, 345 Dyes, 406 Dynamic bonds, 323 Dynamite, 201 Ecgonine, 432 Egg membrane, osmotic pres- sure, 57 Eka-iodoform, 131 Elaterin, 411 Electrical conductivity of solu- tions, 65 Electrolytes, 65 Electrolytic dissociation, 65 Elements in organic compounds, 2 Emodin, 413 Empirical formula, 6, 98 Emulsin, 246, 252, 351 Emulsions, 80 Emulsoids, 81 Enzymes, 141, 180 Enzymes, adsorption of, 95 " , as colloids, 95 460 INDEX Eosin, 373 Epicarin, 410 Epinephrin, 383 Equilibrium, chemical, 175 of ions and mole- cules, 68 Ergotinine, 427 Ergotoxine, 427 Erucic acid, 303 Erythrodextrin, 250 Eseridine, 426 Eserine, 426 Esterification, 174 Esters, 173 Ester value, 206 Ethanal, 151 Ethane, 104, 120 Ethene, 300 Ethereal salts, 166, 178 Ethers, 109, 132 , aromatic fatty, 340 , mixed, 134 , true aromatic, 340 Ethyl acetate, 182 alcohol, 139 amine, 260 benzene, 330 benzoate, 359 bromide, 125 butyrate, 187 carbamate, 267 carbonate, 278 chloride, 125 cyanide, 255 ether, 132 glycollate, 213 nitrite, 265 sulphonic acid, 306 sulphuric acid, 127 Ethylene, 193, 300 " bromide, 193 " " i preparation of, 301 11 lactic acid, 214 Ethylenes, 300 Eucaine, a and /3, 430 Eucalyptol, 314 Eucalyptus oil, 314 Eudoxine, 372 Eugenol, 347 ' ' acetamide, 347 " carbinol, 347 iodide, 347 Eumydrine, 432 Euquinine, 434 Euthalmine, 430 Exalgin, 382 Extraction, 20 Fats, 203 ' ' , vegetables, 204 Fatty acids, 157 " " , volatile, 204 " compounds, synopsis of, 115 Fat values, 205 Fehling's solution, 241 Fermentation, 237, 240 Fire damp, 118 Fischer, Emil, 297 Flashing point of oils, 122 Fluidity, 78 Fluoresceiin, 372 Formaldehyde, 148 Formaline, 148 Formamide, 274 Formic acid, 158 et " series, 158, 187 Formonitrile, 256 Formula, calculation from per- centage composition, 38 Formulae, empirical and struc- tural, 98 Fractional crystallization, 218 Fractional distillation, 13 Freezing-point constants, 60 ' ' depression by so- lutions, 59 Fructose, 231, 235, 238 Fruit sugar, 238 Fuchsin, 379 Fuchsin, acid, 379 INDEX 461 Fuchsin aldehyde reaction, 148 Furan, 414 Furfuraldehyde, 230, 415 Furfurol, 230, 415 Fusel oil, 145 Galactose, 231, 238, 246, 251 test, 246 Galactosamine, 233 Gallic acid, 368 Gallisin, 244 Gall-nuts, 368 Garlic, oil of, 307 Gas, coal, 119 " laws, 41 " , natural, 119 Gases, molecular weight of, 41 Gasoline, 121 Gasoline, fuel value, 122 Gastric juice, 184, 402 Gaultherin, 252 Gay-Lussac's law, 41 Gelatine dynamite, 201 Gelose, 251 Gelseminine, 426 Glucoproteins, 233 Glucosamine, 233 Glucosazone, 235 Glucose, 231, 236, 238 d-Glucose, a and /3, 236 Glucosides, 251 Glucosides, artificial, 253 Glucosone, 236 Glutamic acid, 269 Glutamin, 277 Glutaminic acid, 269 Glutaric acid, 195 Glutol, 149 Glyceric acid, 202, 219, 234 aldehyde, 228, 234 Glycerine, 199 Glycerol, 199 Glycerophosphoric acid, 202 Glycerose, 228 Glyceryl acetates, 206 Glyceryl butyrate, 200 " tribenzoate, 360 11 trioleate, 203 " tripalmitate, 203 " tristearate, 203 Glycin, 268 Glycinamide, 275 Glycocoll, 220, 268, 360 Glycocholic acid, 220 Glycogen, 88, 250 Glycol, 193 " aldehyde, 228 Glycolates, 194 Glycollates, 213 Glycollic acetate, 213 " acid, 194, 212 aldehyde, 194 Glycollid, 214 Glycuronates, paired, 221 Glycuronic acid, 221, 233, 237 Glyoxal, 194 Glyoxylic acid, 194, 219 Gram molecular solution, 50 Gram molecule, 42 Grape sugar, 238 Green soap, 209 Guaiacol, 345, 346 ' ' benzoate, 345 Guanidin, 284 Guanin, 293 Gum Arabic, 251 " benzoin, 358 Gums, 251 Gum tragacanth, 251 Guncotton, 247 Giinzberg's reagent, 348, 402 Gutta percha, 315 Hsematin, 415 Hsematoporphyrin, 415 Haemin, 415 Haemoglobin, 298 Halides, 108 Halogens, detection of, 4, 5 Halogen derivatives of paraffins, 124 462 INDEX Halogen derivatives of benzenes, 333 Headache medicines, 381 Heat of combustion, 121, 137 Heavy oil, 318 Hedonal, 283 Helianthin, 395 Heptoses, 240 Heroine, 439 Heterocyclic compounds, 116, 414 Hexabasic acid, 373 Hexachlorbenzene, 333 Hexamethylentetramine, 264 Hexane, 104, 120, 123 Hexone bases, 270 Hexoses, 231 Hippuric acid, 360 Histidin, 271 Holocain, 382 Homatropine, 426, 432 Homogentisic acid, 371 Homologous series, 104 Homologues of benzene, 329 Hydrastine, 436 Hydrastinine, 436 Hydrazine, 388 Hydrazobenzene, 388 Hydrazones, 148, 235, 352 Hydrion, 172 Hydrocarbons 102 ' ' aromatic, 316 cyclic, 309 ' ' groups of, 102 11 saturated, 103, 117 " , unsaturated, 103, 299 Hydrocinnamic acid, 362 Hydrocyanic acid, 256 Hydrogels, 84 Hydrogen, detection of, 3 1 ' , estimation of, 28 ion concentration, 404 " , nascent, 118 Hydrogenation of oils, 303 Hydrolysis, 157 " , power of acids to cause, 452 Hydrolytic dissociation, 70, 209 Hydrometer, 24 Hydroquinol, 346 Hydroquinone, 346 Hydrosols, 84 Hydroxion, 172 Hydroxyacetic acid, 212 Hydroxy acids, 114, 212 Hydroxybenzoic acids, 363 /3-Hydroxybutyric acid, 218 Hydroxy camphor, 313 Hydroxy compounds, aromatic, 336 Hydroxycymenes, 344 /3-Hydroxyethyl-sulphonic acid, 306 Hydroxyformic acid, 212 Hydroxy hydroquinol, 348 Hydroxyl group, nature of, 136 Hydroxyl, test for, 136, 146 Hydroxy prolin, 271, 415 Hydroxypropionic acids, 214 Hydroxytoluenes, 343 Hyoscine, 426, 432 Hyoscyamine, 432 Hypertonic solutions, 55 Hypnal, 156 Hypnone, 355 Hypotonic solutions, 55 Hypoxanthin, 292 Ichthyol, 307 Identification of substances, 22, 26 Illuminating gas, 119 Imidazole, 414 Imido compounds, 284 Imido group, 114 Indican, 253, 417, 419 Indicators, 399 Indigo, 418 Indigo red, 419 INDEX 463 Indigo, synthesis of, 419 " , white, 419 Indirubin, 419 Indol, 417 Indolaminopropionic acid, 418 Indoxylglycuronic acid, 417 Indoxylsulphuric acid, 417 Ink, 370 Inosite, 310 Inversion, 240 Invertases, 240 Invert sugar, 241, 245 lodal, 130 Iodine, dextrin test, 250 ' ' , glycogen test, 251 ' * , starch test, 249 Iodine value, 206 lodobenzene, 333 lodoform, 129 lodoformin, 131 lodoformogen, 131 lodol, 131. 414 lodothyrin, 298 lonization, 65 " constants, 451 " experiment, 342 " of indicators, 399 Ions, 65 ' ' , electrical charge of, 66 Isatin, 418 Isethionic acid, 306 Isoamyl alcohol, primary, 144 11 , tertiary, 145 " acetate, 179 Iso-butane, 123 Isobutyl alcohol, 144 " carbinol, 144 Isobutyric acid, 185 Isocholesterol, 315 Iso-compounds, 106, 123 Isocyanide reaction, 257 Isocyanides, 256 Isocyclic compounds, 116 Isoleucin, 269 Isomaltose, 237, 244 Isomerism, 98, 106 Isomerism, stereo-chemical, 214 Isomers, 98 Isonitriles, 256 Isosmotic solutions, 56 Iso-paraffins, 123 Iso-pentane, 123 Isopral, 156 Isopropylmetacresol, 344 Isopropylorthocresol, 344 Isoquinoline, 423 Isosuccinic acid, 198 Isotonic coefficient, 57 " solutions, 55 Iso valeric acid, 187 Jervine, 427 Kairine, 422 Kekule', 322 Kerosene, 121 Ketohexose, 232 Ketone acid, 192 Ketones, 114, 189 " , aromatic, 354 11 , mixed aromatic fatty, 354 Ketose, 228, 231, 235 " test, 239 Kjeldahl's method of nitrogen estimation, 38 Koprosterol, 315 Kynurenic acid, 422 Lacmoid, 346 Lactic acid, 139, 214, 234 Lactid, 218 Lactocaramel, 244 Lactones, 219 Lactophenin, 382 Lactosazone, 239 Lactose, 240, 242, 244 Lactylphenetidin, 382 Lsevolactic acid, 217 Lsevulose, 231, 235, 238 Lanolin, 192, 211 Lard, 203 464 INDEX Laurie acid, 187 Lead acetate, 165 " " , basic, 165 ' ' , sugar of, 165 Lecithin, 262 Leucin, 269 Leucomaines, 295 Light oil, 318 Lignin test, 247 Ligroin, 121 Linoleic acid, 304 Litmus, 402 Lobeline, 426 Lowering of freezing-point, 59 Lubricating oil, 122 Lycetol, 264 Lysidin, 264 Lysin, 270 Lysol, 343 Malic acid, 221 Malonic acid, 197 Malt, 141 " liquors, 140 Maltodextrin, 250 Maltosazone, 239 Maltose, 141, 237, 240, 242, 244 Mandelic acid, 362 Mannose, 231 Maple sugar, 243 Marsh gas, see Methane. Marsh gas series, 117 Mass action, 175 Melissic alcohol, 192 Mellite, 373 Mellitic acid, 373 Melting-point determination, 10 Menthol, 313 Mercaptans, 115, 306 Mesitylene, 330 " , preparation of, 331 Mesitylenic acid, 362 Mesotartaric acid, 223 Mesoxalic acid, 222 Meta compounds, 326 Metadihydroxybenzene, 346 Metaldehyde, 151 Metasulphobenzoic acid, 394 Metaxylene, 362 Methanal, 148 Methane, 104, 118 Methane series, 117 Methoxyhydrastine, 436 Methyl, 108 Methyl acetanilide, 382 Methyl acetate, 179 Methyl alcohol, 138 Methylamine, 261 Methylaniline, 378 Methylated alcohol, 142 Methyl carbinol, 139 chloride, 125 ' cyanide, 255 ' ether, 132 ethyl ether, 135 ' glycocoll, 268 ' guanidin, 285 ' guanin, 293 ' hexoses, 231 indol, 417 ' isocyanide, 256 ' orange, 395, 400 Methylene blue, 396 Methyl pentoses, 230 Methylphenylhydrazine, 235 Methylphenyl ketone, 355 Methyl pyridines, 416 " salicylate, 364 ' ' thionin hydrochloride, 396 " violet, 380 " xanthins, 293 Meyer, Victor, method, 44 Microns, 87 Milk sugar, 244 Models representing formulae, 106 Models to represent stereoiso- merism, 223 Mole, 42 Molasses, 243 Molecular disperse solutions, 80 INDEX 465 Molecular weight: Calculated from freezing- point determination, 64 Calculated from osmotic pres- sure, 50 Calculated from vapor den- sity determination, 41 Determined by analysis of derivatives, 40 Determination by depression of freezing-point, 59 Molecular weight of gases and vapors, 41 Molecular weight of colloids, 90 Molisch's test, 234, 254 Monobasic acids, 40, 113 Monobromethane, 125 Monobromisovaleryl-urea, 283 Monochloracetic acid, 170 Monochlorethane, 125 Monochlorhydrin, 200 Monochlormethane, 125 Monoformin, 160 Monohydroxybenzene, 336 Monohydroxybenzoic acids, 363 Monohydroxy dibasic acids, 221 Monohydroxytribasic acids, 226 Monomethyldihydroxyanthra- quinone, 413 Monomethyltrihydroxyanthra- quinone, 413 Mononitrobenzene, 374 Mononitrophenol, 341 Monosaccharides, 227 " , general reac- tions of, 235 Mordants, 408 Morphine, 437 Mucic acid, 233 Multirotation, 236 Murexide, 291 Muscarine, 262 Mustard oil, 307, 343 Mutarotation, 236 Mycoderma aceti, 161 Myristic acid, 187 Naphtha, 121 Naphthalene, 409 Naphthols, 409 /3-Naphthol benzoate, 410 a-Naphthol-orthohydroxytoluic acid, 410 Naphthylamines, 410 Naphthylamine-sulphonic acid, 410 Narceine, 437 Narcotine, 436 Nascent hydrogen, 118 Natural gas, 119 Neo-pentane, 123 Neurine, 264 Neuronal, 283 Nicotine, 429 Nirvanin, 367 Nitriles, acid, 256 Nitrites, 265 Nitrobenzene, 374 Nitrobenzoic acids, 360 Nitrocellulose, 247 Nitro-compounds, 264 ' ' , aromatic, 374 Nitroparaffins, 264 Nitrogen derivatives of paraf- fins, 114, 255 ' ' , detection of, 3 " , estimation by com- bustion, 36 " , estimation by Kjel- dahl's method, 38 tables, 447 Nitroglycerine, 201 Nitroglycerol, 201 Nitrophenols, 341 Nitrous acid, action on amines, 260 Non-electrolytes, 65 Nonoses, 240 Normal compounds, 106 Nosophen, 372 Novaine, 262 Novaspirin, 367 Novatophan, 423 466 INDEX Novocaine, 360 Nucleic acid, 295 Nuclein bodies, 293 Nucleoproteins, 295 Octoses, 240 Oil of bitter almonds, 351 caraway, 344 cinnamon, 354 cloves, 347 eucalyptus, 314 garlic, 307 peppermint, 313 sassafrass, 347 thyme, 332 turpentine, 311 wintergreen, 365 Olefiant gas, 300 Olefins, 300 Oleic acid, 303 Olein, 203 Oleomargarine, 186 Oieo-palmito-stearin, 204 Olive oil, 204 Opium alkaloids, 435, 437 Optical activity, 216 Optical activity of protein de- composition products, 271 Orange II, 395 Orangine powders, 381 Orcein, 347 Orcin, 347 Orcinol, 347 Organic chemistry, definition of, 1 Organic chemistry, preliminary survey of, 101 Organic compounds, synopsis of, 115 Organic substances, solvents of, 7 . Ornithin, 270 Orphol, 410 Ortho compounds, 326 Orthodihydroxybenzene, 345 Orthoform, 367 Orthophthalic acid, 371 Osazones, 235, 238, 245 ' ' , melting-points of, 239 Osmotic cell, 48, 49 Osmotic pressure, 46 Osmotic pressure of colloids, 90 Osmotic pressure of haemoglobin, 90 Osmotic pressure of gelatine, 90 Osmotic pressure, determination of, with red blood cells, 55 Osmotic pressure, effect of tem- perature on, 50 Osmotic pressure, effect of con- centration of solution on, 51 Osone, 236 Oxalates, 196 Oxalic acid, 195 Oxaluric acid, 287 Oxamide, 276 Oxycamphor, 313 Oxygen, calculation of percent- age of, 38 Oxyproteic acid, 298 Oxyquinoline sulphate, 421 Palmitic acid, 187, 303 Palmitin, 203 Palmito-distearin, 204 Papaverine, 435 Paper, 246 Parabanic acid, 287 Para compounds, 326 Paradihydroxybenzene, 346 Paraffin, 122 " derivatives, 107 oil, 122 " series, 117 Paraffins, 104, 117 " , boiling-points, spe- cific gravities, etc., 120 " , heat of combustion of, 121 " , synthesis of, 117 Paraformaldehyde, 148 INDEX 467 Parahydroxymetamethoxyallyl- benzene, 347 Parahydroxytolyl mustard oil, 343 Paraldehyde, 151 Paraminophenol, 382 Paraminosulphonic acid, 394 Paraphenetidin, 382 Pararosaniline, 379 Paratoluic acid, 362 Parchment paper, 246 Pelletierine, 425 Pentane, 120, 123 Pentoses, 229 Pentose test, 230 Peppermint, oil of, 313 Peptides, 296 Peptone, 297 Percentage composition, calcu- lated from analysis, 34 Peronine, 439 Petroleum, 121 ether, 121 ether, specific grav- ity of, 25 Phenacetin, 382 Phenanthrene, 413 Phenazone, 415 Phendiol, 345 Phenetole, 340, 385 Phenocoll, 383 Phenol, 336, 337, 385, 392 Phenol, derivatives of, 340 " , substitution products of, 341 Phenolates, 336 Phenolic acids, 363 Phenolphthalein, 372, 399, 402 " , tautomerism of, 402 Phenol-sulphonic acids, 342, 393 Phenols, 336 11 , diacid, 337, 345 " , monacid, 337 " , triacid, 337, 348 Phenoxides, 336 Phentriol, 348 Phenyl, 329 Phenylacetamide, 381 Phenyl acetate, 341 1 ' acetic acid, 362 " alanin, 269, 371 " amine, 376 11 carbinol, 349 Phenylethyl ether, 340 Phenylhydrazine, 148, 235, 352, 388 Phenylmethyl ether, 340 Phenylpropionic acid, 362 Phenyl salicylate, 365 Phenyltolylketone, 354 Phloretin, 252 Phloridzin, 252 Phloroglucin, 348 Phloroglucinol, 348 Phloroglucin-vanillin reagent, 348, 402 Phosgene, 128 Phosphatides, 262 Phosphine, substitution deriva- tives, of, 264 Phosphorus-containing com- pounds, 262 ' ' , detection of, 5 Phthalic acid, 330, 371 " anhydride, 371 Phthalimide, 372 Physical properties of sub- stances, 22 Physostigmine, 426 Phytosterol, 315 Picnometer, 23 Picric acid, 341 Picropodophyllin, 442 Picrotoxin, 442 Pilocarpidine, 426 Pilocarpine, 441 Pinene, 311 " hydrochloride, 311 Pine oils, 311 Pintsch gas, 119 Piperazine, 264 468 INDEX Piperidine, 428 Pipeline, 428 Plasmolysis, 57 Polarization, 245 Polymerization, 148, 151 Polymers, 148 Polymethylenes, 310 Polypeptides, 296 Polysaccharides, 228, 246 Polyterpenes, 314 Potassium acetate, 165 acid tartrate, 224 antimonyl tartrate, 225 benzene sulphonate, 337, 357, 393 hydroxide, specific gravity table, 449 phenol sulphate, 340 Pressure, osmotic, 46 ' ' , vapor, 450 Primary alcohols, 110, 136 " amines, 257 Prolin, 271, 415 Propane, 105, 120 Propene, 302 Propenol, 302 Propionic acid, 184 Propyl alcohol, 144 ' ' ' ' , secondary, 189 Propylene, 201 a-Propyl piperidine, 429 Protamines, 271 Protein, formation of dextrose from, 233 1 ' , synthesis of, 296 Proteins, classes of, 298 Protocatechuic acid, 368 Prussic acid, see Hydrocyanic acid. Pseudo-catalyst, 180 Ptomaines, 263 Purification of substances, 7 Purin bodies, 292 " nucelus, 292 Purpuric acid, 291 Putrescine, 263 Pyoktanin, 380 Pyramidon, 415 Pyrazole, 414 Pyridine, 416 bases, 415 Pyrimidin derivatives, 294 Pyrimidin ring, 287 Pyrocatechin, 345 Pyrocatechol, 345 Pyrogallic acid, 348 Pyrogallol, 348 Pyroligneous acid, 162 Pyroxylin, 247 Pyrrol, 414 Pyrrolidine, 415 a-Pyrrolidine-carboxylic acid, 271 Pyrrolidine derivatives, 430 Pyruvic acid, 140, 192 Quantitative analysis, 28, 40 Quaternary bases, 114, 260 Quinalgen, 422 Quinidine, 434 Quinine, 420, 434 " bisulphate, 440 Quinine-urea hydrochloride, 434 Quinoid structure, 402 Quinol, 346 Quinoline, 420 Quinones, 398 Racemic lactic acid, 217 " substances, 216 ' ' tartaric acid, 223 Reduction tests, 235 Reichert-Meissl value, 205, 207 Resorcin, 346 Resorcinol, 346 Reversible reactions, 175 Rhamnose, 230 Rhein, 413 Rhigoline, 121 Ricinoleic acid, 304 INDEX 469 Rochelle salt, 225 Rosaniline, 379 Rotation of polarized light, 216 Rotatory power of sugars, 236, 245 Rubber, 314 Saccharates, 244 Saccharic acid, 232 Saccharin, 394 Saccharose, 241, 243 Safrol, 347 Sajodin, 188 Salicin, 252 Salicylic acid, 363 combustion anal- ysis of, 32 Salicyl-sulphonic acid, 393 Saligenin, 252, 351 Salipyrin, 367 Salol, 365 Salophen, 366 Salvarsan, 396 Sandalwood oil, 314 Sanguinarine, 426 Sanoform, 366 Santonin, 410 Santoninic acid, 410 Saponification, 208 value, 205 Saponin, 253 Sarcolactic acid, 217 Sarcosin, 268 Sassafras oil, 366 Saturated hydrocarbons, 103, 117 Schiff's reagent, 154 Schweitzer's reagent, 246 Scopolamine, 432 Scopolin, 432 Secondary alcohols, 110, 189 ' ' amines, 258 Selective permeability, 57 Semipermeable membrane, 47 Serin, 268 Side chain, 106, 356 Sidonal, 264 Silk, artificial, 248 " , viscose, 248 Sinalbin, 253 Sinigrin, 253 Sinipine, 426 " Six hundred and six," 396 Skatol, 417 Skatoxylsulphuric acid, 418 Smokeless powder, 248 Soap, castile, 209 ' , cleansing action of, 209 ' , green, 209 ' , hard, 209 ' , resin, 209 ' , soft, 209 1 , Venetian, 209 Soaps, 209 Sodium acetate, 165 " amalgam, 220 ' ' hydroxide, specific grav- ity table, 448 " methyl, 131 " methylate, 137 " oleate, 209 " phenylcarbonate, 363 ' ' potassium tartrate, 225 ' ' salicylate, 364 Solute, 47 Solutions, 47, 59 11 , colloidal, 81 " , electrical conductiv- ity of, 65 " , isotonic, hypotonic, hypertonic, 55 1 1 , obedience to gas laws, 50 Solvents, 7 Sorbitol, 232 Sparteine, 427, 430 Spatial representation of mole- cules, 215 Specific gravity determination, 23 " " of liquids, 23 470 INDEX Specific gravity of solids, 24 " "' tables, 445, 448, 449, 450 Spermine, 264 Starch, 249 ' ' , soluble, 88 Steam distillation, 16 Stearic acid, 187, 303 Stearin, 203 Stereochemical isomerism, 214 Stereoisomerism, 214 Sterins, 315 Stovaine, 360 Strophanthin, 253 Structural formula, 98 Structural formula of acetic acid, proof of, 164 Strychnine, 435 Stypticin, 437 Sublimation, 13 Submicrons, 87 Substituted ammonias: Primary, 257 Secondary, 258 Tertiary, 258 Succinic acid, 197 Succinic anhydride, 198 Succinimide, 284 Sucrose, 241, 243 Sugars; comparative reducing power of, 241 ' ' , estimation of, 241 1 ' , specific rotation of, 245 ' ' , tests of, 239 Sulphanilic acid, 394 Sulphobenzoic acids, 360 Sulphocyanic acid, 257 Sulphonal, 307 Sulphones, 306 Sulphonic acids, 115, 306 " , aromatic, 391 " chlorides, 391 Sulphonmethane, 307 Sulphur alcohols, 115, 306 ' ' -containing amino acids, 272 Sulphur, derivatives of paraffins, 115, 306 ' ' , detection of, 3 11 ethers, 115, 306 Suprarenin, 384 Surface tension, 71, 88 Suspensoids, 81 Synthesis, 6 Tannacol, 370 Tannalbin, 370 Tannic acid, 88, 368 Tannigen, 370 Tannins, 370 Tannoform, 370 Tartar emetic, 225 Tartaric acids, 222 Tartronic acid, 202, 221, 290 Taurin, 272 Taurocholic acid, 221 Tautomerism, 290, 401 Terpenes, 310 Terpin, 312 Terpin hydrate, 312 Tertiary alcohols, 110, 192 " amines, 258 bases, 114, 425 Tetrabromfluorescein, 373 Tetrachlormethane, 120, 127 Tetrathylamrnonium hydrox- ide, 260 Tetra-iodo-methane, 131 Tetra-iodo-pyrrol, 414 Tetramethoxybenzylisoquino- line, 435 Tetranitrol, 202 Tetraphenylhydrazine, 381 Tetronal, 307 Tetrose, 229 Thalline, 422 Thebaine, 439 Theobromine, 294, 441 Theophylline, 441 Thio alcohols, 306 Thiophene, 319, 414 INDEX 471 Thiophenol, 391 Thiosinamine, 308 Thyme, oil of, 332, 344 Thymin, 295 Thymol, 343 Toluene, 329 Toluene-sulphonic acids, 391, 393 Toluic acids, 362 Toluidines, 378 Toluol, 329 Tolyl carbinol, 351 Tragacanth, gum, 251 Traube's synthesis, 287 Tribrommethane, 127 Tribromphenol, 341 Trichloracetic acid, 170 Trichloraldehyde, 154 Trichlorhydrin, 200 Trichlorlactamide, 289 Trichlormethane, 120, 127 Trichlortertiary butyl alcohol, 191 Tricresol, 343 Trihydroxybenzene, 348 Trihydroxybenzoic acid, 368 Triiodoacetone, 191 Triiodomethane, 129 Trimethylamine, 261 Trimethylene, 310 Trinitrobenzene, 326 Trinitrocellulose, 248 Trinitro phenol, 341 Trinitrotoluene, 376 Trional, 307 Trioses, 228 Triphenylamine, 380 Triphenylmethane dyes, 380 Trisaccharides, 228, 246 Tropacocaine, 433 Tropaeolin OO, 396 Tropic acid, 431 Tropine, 431 Tryptophan, 220, 271, 418 Turpentine, 311 Tussol, 415 Tyrosin, 269, 371 Ultrafiltration of colloids, 86 Ultramicroscope; 87 Unsaturated hydrocarbons, 103 Uracil, 295 Urates, 291 Urea, 277 ' ' , freezing-point determina- tion of molecular weight. 62 " , nitrate, 281 " , oxalate, 281 ' ' , specific gravity of, 25 " , synthesis of , 1,278,281 Urethane, 267 Uric acid, 286, 293 ' ' , tautomerism of, 290 Urine, depression of freezing- point of, 64 Urinometer, 24 Urotropine, 264 Vacuum distillation, 16 Valence of elements in organic compounds, 2 Valerianic acid, 187 Valeric acid, 187 Valin, 269 'Vanilla, 368 VaniUic acid, 368 VaniUin, 368 Vapors, molecular weight of, 41 Vapor tension table, 450 Vaseline, 122 Vegetable bases, see Alkaloids. Veratrine, 427 Veronal, 282 Victor Meyer's vapor density method, 44 Vinegar, 162 Viscosity, 77 ' ' of colloidal solutions, 89 number, 79, 207 Von Baeyer's reagent, 301 Water-gas, 119 472 INDEX Waxes, 192 Weight normal solutions, 50 Westphal's balance, 23 Whiskey, 140 Wines, 140 Wintergreen, oil of, 365 Wood alcohol, 138 " turpentine, 311 Xanthin, 293 " bodies, 293 Xylene, meta, 330, 331 Xylenes, 330 Xylidines, 378 Xylol, 330 Xylose, 229, 233 Yeast, fermentation by, 141 Yohimbine, 426 Zinc methyl, 131 Zymase, 141 RETURN CIRCULATION DEPARTMENT TO* 202 Main Library LOAN PERIOD 1 HOME USE 2 3 4 5 6 ALL BOOKS MAY BE RECALLED AFTER 7 DAYS 1 -month loans may be renewed by calling 642-3405 6-month loans may be recharged by bringing books to Circulation Desk Renewals and recharges may be made 4 days prior to due date DUE AS STAMPED BELOW APR ^V Q i UNIVERSITY OF CALIFORNIA, BERKELEY FORM NO. DD6, 60m, 12/80 BERKELEY, CA 94720 UNIVERSITY OF CALIFORNIA LIBRARY " : .yt -. ?