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Sage 1891 97»4 arV10443 Organic chemistry, Cornell University Library 3 1924 031 268 448 oiin,anx WW B Cornell University ^^' h) Library The original of tliis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/cletails/cu31924031268448 ORGANIC CHEMISTRY INCLUDING CERTAIN PORTIONS OF PHYSICAL CHEMISTRY MEDICAL, PHARMACEUTICAL, AND BIOLOGICAL STUDENTS (WITH PRACTICAL EXEECISES) HOWARD D. HASKINS, A.B., M.D. Associate Professor of Organic Chemistry and Bio-Chemistry, Medical Department, Western Reserve University. SECOND EDITION FIRST THOUSAND NEW YORK JOHN WILEY & SONS London ; CHAPMAN & HALL, Limited 1913 Copyright, 1907 BY H. D. HASKINS AND J. J. R. MACLEOD Copyright, 1912 BY HOWARD D. HASKINS THE eClENTIFIC PRESS ROaeRT DHUMMOND ANO COMPANV BROOKLYN, N. V. 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 pharmacology. H. D. Haskins. July 1, 1912. 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 com- position of animal tissues and fluids, and to the physico- chemical laws which govern, or at least influence, many physiological processes. The discovery of the chemical constitution of the pvu-in bodies, of many of the urinary constituents, and of sugars and fats, as well as the new theories of solution and catalysis, has revolutionized the teaching of biological and clinical chemistry; and in pharmacology 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.^ As taught in the regular college classes in organic chemistry, the subject certainly absorbs too great a * The recent application by Arrhenius of certain phjrsico- chemical 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. V yl PREFACE. proportion of the medical student's time, and much is included in the course which has no bearing on 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 wliich 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 portion of the book considerable attention is given to a. descrip- tion 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 diffculties. A chapter 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 atten- tion 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. Numerous prac- tical exercises accompany the text, and these have been chosen .and arranged so as to occupy about four PREFACE. vii hoiiTS of laboratory work per week for a thirty-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 cycUc compounds and the more com- plicated of the benzene derivatives 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 beUeve that by conducting an elementary analysis and by doing cryoscopic experiments with Beckmann's ap- paratus, as also by 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 futtire work. Our experience is, also, that students of whom laboratory work is required get a grasp and under- standing of the subject of organic chemistry such as others rarely acquire. H. D. Haskins. J. J. R. Macleod. April, 1907. CONTENTS. CH-\PTER I. PAGE The Nature and Composition op Organic Compodnds 1 CHAPTER II. Purification and Identification op Substances 7 CHAPTER III. Elementary Analysis 25 CH.\PTER IV. Moi^cuLAR Weight Determination. The Nature of Solu- tions. Osmotic Pressure. Ionization. Colloid.al Solutions. Surface Tension. Viscosity 36 CHAPTER V. FoRiruL.E, Empirical and Structur-al. Isomerism 76 Synopsis of Ch.\pters I-V 78 CH.APTER VI. Preliminary SuR^'EY op Organic CHEnnsTRY 79 Synopsis op Fatty Compounds 92 CHAPTER VII. Saturated Hydrocarbons. Meth-vne Series 94 ix X CONTENTS. CHAPTER VIII. PAOB Halogen SuBSirniTiON Products of the Paraffins 101 CHAPTER rx. Bthehs • • 109 CHAPTER X. Primary Alcohols 112 CHAPTER XI. Aldehydes 122 CHAPTER XII. Fatty Acids and Ethereal Salts. Further Observations IN Physical Chemistry 133 CHAPTER XIII. Secondary and Certain Other Monacid Alcohols. Ketones Ig3 CHAPTER XIV. Diacid Alcohols and Dibasic Acids 167 CHAPTER XV. Triacid Alcohols, Fats, and Soaps I73 CHAPTER XVI. Nitrogen Derivativbs. (Also Phosphorus and Sulphur Compounds) J84 CHAPTER XVII. Mixed Compounds. Hydroxy-acids 196 CONTEXTS. XI CHAPTER XVIII. PACK Mixed Compounds (Continued). Amido Acids and Acid Amides 211 CHAPTER XIX. Mixed Compounds (Continued). Acid Imides. Complex Amido .\xd Imido Compounds, Including Polypeptides 229 CHAPTER XX. Mixed Compounds (Continued). C.\rbohydrates and Glucosides 243 CHAPTER XXI. Unsaturated Htdrocahbons and Their Derh'atives 268 CHAPTER XXII. Cyclic and bi-cyclic Compounds 275 CHAPTER XXIII. The Aromatic Hydrocarbons 281 CHAPTER XXIV. Aromatic Halogen Derivatives 298 CHAPTER XXV. Aromatic Hydroxy Compounds 301 CHAPTER XXVI. Aromatic Acids 318 CHAPTER XXVII. .Aromatic Nitrogen and Sulphur Deriv.\tives 327 FA.QB . 343' xii CONTENTS. CHAPTER XXVIII. Mixed Aromatic Compounds CHAPTER XXIX. Mixed Aromatic Compounds (Continued). Also Indica- TOES AND Dyes ^^° CHAPTER XXX. Aromatic Compounds Having Condensed Rings 368 CHAPTER XXXI. Heterocyclic Compounds 373 Synopsis of Aromatic Compounds 380 CHAPTER XXXII. Alkaloids and Drug Principles 382 APPENDIX. Note to the Instructor 401 Reference Tables: I. Specific Gravity and Percentage of Alcohol 403 II. Weight in Milligrams of 1 c.c. of Moist Nitrogen at Various Temperatures and under Various Pressures . 405 III. Specific Gravity and Percentage of NaOH in Aqueous Solution 406 IV. Specific Gravity and Percentage of KOH in Aqueous Solution 407 V. Acetic Acid, Specific Gravity and Freezing-point at Various Concentrations 408 VI. Vapour Tension of Water and of 40% KOH at Various Temperatures 408 VII. Dissociation Constants of Certain Weak Acids 409 'N'lII. Dis.sociation Constants of Certain Bases 409 IX. Power of Certain Acids to Cause Hydrolysis 410 CONTEXTS. Xin ILLUSTRATIONS. FAGB Fig. 1. Melting-jx)int Apparatus 10 2. Sublimation Apparatus — after Gattermann 13 3. Fractional Distillation Apparatus — after Gattermann.. 14 4. Fractionating Column — after Gattermann 15 5. Steam Distillation Apparatus — after Gattermann 16 6. Vacuimi Distillation Apparatus — after Gattermann. . . 16 7. Boiling-point Flask 17 8. Picnometer ,., 20 9. Westphal's balance 20 10. Hydrometer 21 11. Combustion furnace 26 12. Calcium Chloride and Potash Absorption Apparatus — after Gattermann 27 13. Mixing Tube 29 14. Nitrogen Burette — aft«r Gattermann 33 15. Victor Meyer's ^'apour Density Apparatus — after Walker 39 16. Palladium Chamber 42 17. Beckmann's Apparatus and Thermometer — after Walker 53 18. Flashing-point Apparatus — ^after Remsen 99 19. Ethyl Bromide Apparatus — after Gattermann 103 20. Aldehyde Apparatus — after Fischer 128 21. Acetjl Chloride Apparatus — after Gattermann 144 22. Tartaric Acid Models, lUustiating Stereoisomerism. . 206 23. Sodium Ammonium Racemate Crystals — after HoUc- man 208 24. Ethylene Bromide Apparatus — after Gattermann 269 25. Collie's Benisene Model 289 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 chemist into groups, a group comprising all the compounds of some particular element. Thus we have the iron group, the sulphur group, and so on. On account, however, of the great number i of compounds containing the element carbon, the group of carbon compounds is set apart for consideration as a special branch of chemistry. Organic chemistry is that branch: it is the chemistry of carbon compounds. This definition is, however, not strictly accm-ate, 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 organ- isms, by so-called vital activity. That such a notion ' Over 112,000. 2 ORGANIC CHEMISTRY. is untenable was first shown by Wohler, who, in 1828^ obtained urea — the main organic constituent of urine— by simply evaporating an aqueous solution of ammonium iso-cyanate, his intent being to recrystallize the latter salt (p. 224). 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 compounds carbon may exist in combination with one, two, three, four, or even five other elements. The most important elements present in organic compounds, together with their atomic weights and valences, are as follows : Carbon, C atomic wt. 12, valence IV. Hydrogen, H . . . . " Oxygen, 0... " ' Nitrogen, N . . . " Phosphorus, P . . . . " Sulphur, S " Some important compounds contain the halogens (CI, 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 finding the percentage composition of the compound and observing that the sum of the per cents of all the other elements is less than one hundred. 1, ' I. 16, ' II. 14, " III and V. 31, " III and V. 32, " II,IVandVI ORGANIC COMPOUNDS. 3 Experiments. Detection of carbon, hydrogen, nitro- gen, sulphur, and phosphorus. (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 mix- ture 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 condense on the cool parts, showing the presence of H.^ Cloudiness in the baryta is due to carbon dioxide, forming BaCOa, and indicates the presence of C. By heating CuO it is reduced; its oxygen combines with the C and H of the organic sub- stance to produce CO2 and H2O. (2) N and S. (a) Triturate in a mortar some dry albumin with twenty times as much soda-lime,^ transfer the mixture to a test-tube, and heat over a flame. Test the vapour that appears for ammonia, the presence of which proves the existence of N in the compound examined. (b) 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 small beaker containing 10 c.c. of distilled water. The tube breaks, and NaCN and Na2S go into solution. Filter and diAdde the filtrate into portions A, B, C, and D. To A add NaOH 1 Water of crjrstaUization must be removed before testing for hydrogen. * Soda-lime is made by gradually adding powdered quick- lime to a saturated solution of caustic soda with constant stirring. 4 ORGANIC CHEMISTRY. until Strongly alkaline, then a few drops of freshly made FeS04 solutioni and a drOp of Fe2Cl6 solution. Boil this mixture two minutes, cool, and acidify with HCl. The appearance of a greenish-blue colour or a precipitate of Prussian blue indicates N. To B add a few drops of a fresh solution of sodium nitroprusside;^ a reddish- violet colour 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. NeutraUze D with HCl; add a few drops of Fe2Cl6 solution: a red colour, which is removed by HgCla, is caused by the presence of sulphocyanide. If sulphocyanide is not formed in examining an organic compound by this method, halogens may be tested for in the filtrate by boiling some of it with one-tenth volume of concentrated HNOa (HCN or HzS driven off — prolonged boiling may be necessary to remove all the HCN) and then testing with AgNOs (precipitate of AgCl, AgBr, or Agl). In this test iodine and bromine are set free by the nitric acid and can be detected by odour and colour. If it is desired to detect N, S, or halogens in a liquid it is best to drop the Uquid on to melted sodium contained in a test-tube which is held vertically by being thrust through a hole in an asbestos pad. (3) P. Mix some dry nucleoprotein (or dry yeast) with twenty parts of fusion mixture (1 part Na2C03 + 2 parts KNO3). 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 evaporat- ing dish. Add HCl until neutral and filter. To half of ' Sodium ferrocyanide is formed by this treatment. ' Formula = Na,Fe(CN) eCNO V ORGANIC COMPOUNDS. 5 the filtrate add NH4OH until strongly alkaline, then add magnesia mixture. 1 The phosphates, formed by the oxidation of the phosphorus of the compound, cause a white precipitate. To the other half of the filtrate add HNO3 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 present in the organic compound that he is investigating, the chemist next proceeds to its more thorough examination. He first estimates the percentage amounts of the vari- ous elements contained in the substance, and then he determines its molecular weight. He is able from these data to calculate the empirical ^ formula. But more than one substance may have this same formula; there- fore 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 Unked together. And, finally, by causing simpler substances, the structure of whose molecules is known, to become united (synthesis), he endeavours to produce a substance having the same molecular structure as his compound. •Magnesia mixture is made as follows: Dissolve 55 gm. of pure MgCls crystals and 70 gm. NH4CI 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. ammonium molybdate in 500 c.c. of water and add 500 c.c. of HNO3 of specific gravity 1.2. ' The empirical formula gives merely the total number of atoms of each element in one molecule, as CsHuOs (see p. 76). 6 ORGANIC CHEMISTRY. If his synthetic compound 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 compound. 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 neces- sary 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 ascertained. This will be done 'm the chapter that follows. 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, svblimation, distillation, and dialysis. Crystallization. The basis of this method is the fact that different substances are not usually soluble to an equal extent in the same solvent. For example, acetanilide can be separated from dextrcjse by dissolving the mixtiu-e of these two in hot water : on cooling the resulting solution, the acetaniUde 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 separa- tion and purification of organic compounds is invaluable, it will be well to detail specific directions for carrying it out. (1) Carefully select a suitable solvent. Put small quantities of the substance to be purified into several test-tubes; add to each a different solvent — those most commonly used are water, alcohol, ether, chloroform, benzol, petroleum ether, acetone, and 8 ORGANIC CHEMISTRY. glacial acetic acirl. Discard those which dissolve the substance readily. Heat each of those that remain. Choose the solvent which when hot dissolves the sub- stance 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 prevent rapid cooling by wrapping the beaker with a towel. (6) Cover the beaker with a piece of filter-paper to prevent condensation-drops 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 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 suflBciently insoluble in ' 5, 6, and 7 may be disregarded except when the form of the crystals is to be studied. PURIFICATION OF SUBSTANCES. 9 the cold solvent, crystallization may be brought about by slow evaporation in a wide crystallization dish which is loosely covered, as with fractional crystallization. (9) Collect the crystals on a suction-filter (reject the crystals that have crept above the surface of the liquid), 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. Com- pletely 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 and recrystallize. Repeat the process until the filtrate from the crystals no longer reduces Fehling's solution.^ At least three crystalfizations should be carried through. Save the pure white crystals. After drying them in a desic- cator a determination of the melting-point may be made (see below) . To test the purity of the crystals their melting-point is determined. The method of making a melting-point determination ^\all be described in the experiments that follow. Pure crystals melt quite sharply and com- pletely, i.e., they become completely melted within 0.5° to 1°. The crystals may be considered pure when, » Fehling's reagent consists of an alkaline solution of cupric hydroxide, the latter being held in solution by means of Rochelle salt. The reagent is of a deep-blue colour, and when it is boiled with even a trace of dextrose a red precipitate forms in it. 10 ORGANIC CHEMISTRY. after repeated crystallization, 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° i). Sulphuric acid is used for higher temperatures (up to 280°) . For still higher temperatures paraffine is used. The thermometer should be one with the scale engraved on the stem. The crystals should be powdered and thoroughly dried in a desiccator. *M Experiment. Make melting-point tubes by heating a small glass tube of 4 mm. diameter in a flame until red, then suddenly drawing it out. A capil- lary tube about 1 mm. in diameter is thus obtained. Break into lengths of 6-8 cm. and seal one end of Fig- 1. each. Put into such a tube some powdered chloral hydrate which has been dried in a desiccator. Gentle scratching with a file 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 thermometer 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 indi- cation of melting (beginning transparency or collapsing 'All temperatures given in this book are centigrade) PURIFICATIOX OF SUBSTANCES. U against the wall of the capillary tube of any portion of the crystalline substance) also the temperature of actual fusion. Into another capillary tube put pure dried powdered urea;i attach the tube to a thennometer with a fine platinum wire, adjusting it as above. The bath in this case should be pure H2SO4 containing 30% of K2SO4 (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 ther- mometer in the flask, with its bulb dipping into the bath. In a similar manner suspend another thermometer to take the temperature of the air above the H2SO4 Heat gradually. When melting occurs, place the bulb of the second 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 H2SO4 (=L in the formula). The correction which must be added to the observed reading (which is T) on account of the stem of the thermometer and mercury thread being cooler than the bulb can be calculated by the formula: i(!r -0(0.000154) .2 The corrected 3 melting- point of pure urea is 132.6°. 1 Where "pure urea" is called for it is best to prepare it by recrystallizing some urea from hot absolute alcohol. 2 The coeflScient of expansion of mercurj'- in glass in 0.000154. 'The melting-points marked "corrected" are quoted from H. Meyer's Analyse und Konstitution der organischen Verbind- imgen. 12 ORGANIC CHEMISTRY. 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, soUdly packed. The initial heating may be rapid until a temperature 20° below the melting-point is reached, then 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 hquid insures greater accuracy. Such an apparatus can be con- 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 albohne (liquid vaseline) to a depth of 5 cm., and fill the beaker for nine-tenths of its depth with the same hquid. 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 approaching the melting-point, stir steadily. An air temperature of only 3-7° below the oil temperature is secured, hence it is unnecessary to calculate a correction. A method of purification applicable to certain solid substances is sublimation. A substance sublimes when it passes readily from the solid state to a vapour. The method is carried out as follows. A watch-glass or evaporating dish containing the substance is covered with filter paper which has several pin-hole perforations. A funnel which is of a size to fit neatly is inverted over this, the stem being loosely plugged with cotton PURIFICATION OF SUBSTANCES. 13 Fig. 2. The dish is heated gradually until vapour passes into the upper chamber of the apparatus and condenses on the cool walls of the funnel (see exp., p. 321). 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 em- ployed (i.e., at a temperature at which the substance itself readily vaporizes), simple distillation suffices. "WTien, however, a mixture of vola- tihzable liquids is dealt with, fractional distillation has to be resorted to. This method is described in the following experiment. Certain mixtures cannot be resolved into their constituents in the pure state by fractional distillation, such as a mixture of water and alcohol, or methyl alcohol and benzol Experiment. Set up a distillation apparatus as shown in the diagram. Into the fractionating flask — a flask having a branch tube fused into the neck as a delivery-tube for the vapour — ^pour through a funnel about 300 c.c. of 50% alcohol, and drop in a couple of 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 vapour, 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 14 ORGANIC CHEMISTRY. liquid. Heat on a water bath. Have four clean dr}- receiving flasks ready and labelled. In the first flask collect all the distillate coming over while the ther- mometer registers a temperature between 78° and 83°. Now dry the outside of the fractionating 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 FiQ. 3. is to catch the distillate between 88° and 93°. The last flask recei\'cs all that distils over above 93°. (Do not distil 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 fractionating flask or a small flask with a bulbed column attached as shown in the diagram. Pour into it the fluid in flaok number one and use the latter as the first receiving flask for the distillate. When the temperature reaches 80° pour the contents of flask number two into the fractionating flask, and when the temperature again PURIFICATION OF SUBSTANCES. 15 Fig. 4. 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 fractionating flask, and distil until the temperature reaches 88°. Determine the per cent of alcohol in these three fractions by taking the specific gravity of each with Westphal's balance (see p. 21), and comparing with the table (p. 403). By repeated fractionating 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, redistil 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- perature of at least 100°. By this means substances which boil even above 200° can be obtained in the distillate, mixed, of course, with a large quantity of water (see Fig. 5). (Compare phenol, p. 303). Vacuum distillation is employed in certain cases, particularly when it is desirable to lower the boiling- point in order to prevent any decomposition of the substance. Many substances decompose at a tempera- ture below their boihng-points. The distilling appara- tus is closed up air-tight except for a finely pointed tube which dips below the surface of the heated liquid 16 ORGANIC CHEMISTRY. and, passing through the stopper, is open to the air: through this tube fine bubbles of air keep the contents of the fiask in commotion and prevent bumping. The receiving flask is connected with a suction-pump. A Fig. 5. reduction of pressure in the apparatus to 30 mm. of mercury (atmospheric pressure being about 760 mm.) will usually lower the boiling-point of a high-boiling Fig. 6. substance by nearly 100°. An ordinary suction-pump is usually quite satisfactory for lowering the pressure (see fig. 6). PURIFICATION OF SUBSTANCES. 17 The test of purity of a substance that distils is constancy of boiling-point. If, after repeated fractional distilla- tion, a material is obtained which has the same boihng- point each time and which distils over completely at that temperature, it is most likely a pure substance. Experiment. The boiling-point flask should be either a long-necked fractionating flask which has the side tube coming off very high up I near the cork, or an ordinary fractionating flask into whose neck is fitted an open tube slightly expanded 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 slipping into the chamber of the flask (see fig. 7) . In such an apparatus the va- pour passes up to the cork, then descends outside the tube, heating the stem of the ther- mometer for the whole length of the mercury column, the thermometer being lowered suflficiently 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; sup- port the flask on wire gauze (it is advisable to inter- pose 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 vapour passes freely into the condenser, note the temperature. 18 ORG ASIC CHEMISTRY. Continue distillation until the temperature has remained constant for at least five minutes. Take the reading a,s the boiling-point. No correction is necessary except for barometric pressure. This correction can be cal- culated approximately by adding to the observed boihng-point 0.038° for each mm. below 760 mm. barometric pressure or subtracting 0.038° for each mm. above thisi. The boiling-point of chloroform at 760 mm. pressure is 61.2° (corrected)^. The author has devised a simple apparatus by which the boiling-point can be determined under standard pressure, avoiding calculation of a correction.' The special distilling flask (Fig. 7) is connected with an air-tight condensing apparatus, a filtering flask (as receiver) being fitted onto 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 distilUng apparatus, as suggested below) of the older type which is 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 ' If the boiling-point is aroimd 100° the factor of correction is 0.044, if 150° it is 0.05, if 200° it is 0.056 and 250° it is 0.062. For water, alcohol, organic acids, and other liquids whose mole- cules become associated (p. 60) 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. 'The boiling-points marked "corrected" in this book are those given in Traube's Physico-chemical Methods. 'Smith and Menzies have recognized the desirability of securing the boihng-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 which is tied to a thermometer, and is submerged in a bath. IDENTIFICATION OF SUBSTANCES. 19 or lowering this tube, the pressure in the distilling apparatus as recorded by the barometer can be brought to any height 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 mercury of the barometer is at 0°. For example, if the temperature of the room is 15°, the apparent pressure in the apparatus must be 762 mm. (glass scale, 761.9 mm. if bra; J scale), in order to get the boiUng-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 which is stable and not inclined to absorb moisture (as benzene), the apparatus can be arranged to eUminate the barometer by connecting a second air-tight distilling apparatus in which to boil the liquid that is uiider examination. Now regulate the pressure so that the Uquid of knuvm boiUng-point distils at a temperature corresponding to standard pressure as previously determined (read to 0.1°), then the temperature at which the other liquid distils wiU be the boihng-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. Dialysis is occasionally employed for purification purposes, especially in bio-chemistry. It depends on the well-known fact that crystalloids can diffuse through animal membranes or parchment paper, whereas colloids cannot. Th"as, . to separate sodium chloride from egg proteid a solution containing these is placed in a dialyser suspended in pUre running water: the sodium chloride diffuses out, leaving the egg proteid in the dialyser. IDENTIFICATION OF SUBSTANCES. ■ When the substance has been purified by the above methods, identification may be attempted. For this 20 ORGANIC CHEMISTRY. purpose its -physical properties are studied; its colour, odour, and taste are carefully noted, and determinations are made of its melting-point, boiling-point, crystalline form, — including measurement 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. Next to the first five properties mentioned, the most universally useful one for purposes of identifica- tion is specific gravity. The method of determining this we will describe here. Those of the other properties not already described will be found in one or another of the larger laboratory manuals.^ The specific gravity of liquids may be found by several different methods. 1. The weight of equal vol- umes of the liquid and of water may be successively ^=^^=71 A=^ Fig. 8. ■Fia. 9. determined in a special stoppered bottle called a picnorrir ' Gatterman. The Practical Methods of Organic Chem- istry. Translated by Schober. MuUiken. Identification of Pure Organic Compounds. Lassar-Cohn. Laboratory Manual of Organic Chemistry; also, Arbeitsmethoden fiir organisch-chemische Laboratorien. IDENTIFICATION OP SUBSTANCES. 21 eter. The temperature of both fluids at the moment of weighing must be reported. The temperature of the water taken as the standard 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 differ- ent sizes are used on this balance, each one represent- ing a different decimal place in the specific gravity. This instrument gives the specific gravity of the hquid at the temperature of observation | compared with pure water at 15°. 3. The hydrometer is another empiiioally 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 fluid, so that the surface comes to a certain mark on the stem, and the figures which are read off at that mark indicate the specific gravity (see fig. 10). The urinometer is a hydrometer for use with uiine. The specific gravity of a solid can be found by weighing it in the air, then reweighing it while immersed in water. This method has very p^^ j„ little apphcation in organic chemistry. The specific gravity of crystals or email solids can be de- termined by placing an acciu-ately weighed quantity oi" them in a picnometer filled ^^■ith some liquid in which they are insoluble (see exp. below) . 22 ORGANIC CHEMISTRY. 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 reweigh. When weighed, note the tem- perature as indicated by the thermometer in the stopper, also make sure that no 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 recording specific gravity report the temperature of observation; for ex- 18° ample, petroleum ether -St^o= 0.7 means that the spe- cific gravity of petroleum ether at 18° is 0.7 when com- pared with water at 15°. Also determine the specific gravity of the ether with the Westphal's balance. (6) Specific gravity of urea. Weigh a Httle test-tube which contains pure dry urea crystals. Remove the stopper of the picnometer used in (a); pour the urea into the petroleum ether. Tap the picnometer to cause the air adhering to the crystals to be dislodged. Now fill the neck with more petroleum ether, insert the stopper as before, and reweigh. The petroleum ether must be at the same temperature as in (a). Reweigh the urea tube; by deducting this weight from the pre- N'ious one find the weight of the urea in the picnometer. IDE.\TIPICATIO\ OF SUBSTAXCES. 23 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 im- mersed in petroleum ether (6); the diflFerence is the weight of the petroleum ether displaced. Divide this by the specific gravity of petroleum ether; the result indi- cates the displacement in cubic centimetres, 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 ^ of boiling-points, melting-points, specific gravities, etc. Generally an accurate determination of the boiling- or melting-point and of the specific gravity will definitely locate the substance. When deahng with a hquid it is advisable, if there exists any doubt about the nature of the substance, to determine the specific gravity at several different temperatures. When reljning 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 di.Terent temperature. Therefore, mix some of the • Such tables may be found in Physikalisch-chemische Tabellen by Landoldt and Bomstein, Chemiker-Kalendar by Biedermann (yearly editions), ^Melting and Boiling Point Tables by Cametty. 24 ORGANIC CHEMISTRY. 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 iden- tification has been completed. If the substance is still unknown or cannot be posi- tively 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 present in a compound is made by combustion in the presence of cupric oxide, the end-products of combustion 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 diflBcultly fusible glass having an inside diameter of about 1.5 cm. This tube should be 10 cm. longer than the fm-nace 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 roU or spiral of copper gauze is in- serted and pushed in 5 cm. from the end, moderately coarse cupric oxide (of wire form) is poured into the other end imtil it occupies 35^0 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 ^ intimately with fine cupric oxide ' The substance may be placed m 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, and this is placed in the combustion-tube. 25 ELEMEXTARY A\ALYSIS. 27 (wire form) in the manner described in the experiment below, then follows a short copper spiral (which has a wire loop attached) and finally some coarse cupric oxide. 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 whicli is connected with the apparatus for purifying the incoming air or oxygen. Fig. 12. The absorption apparatus which collects the products 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 28 ORGAXIC CHEMISTRY. 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 tan be used for the combustion process. Pvire 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 absorp- tion 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 appa- ratus (see fig. 11). It first bubbles through a strong solu- tion of caustic potash, which removes most of the carbon dioxide; then passes through a large U-tube or drymg- 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 moisture.^ 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 produced, also any volatilized material which has not been oxidized, and brings them into contact with the coarse copper oxide, which completes the oxidation; thus the stream when it reaches the end of the tube consists of air or oxygen containing carbon dioxide and water-vapour. In passing through the calcium 1 To insure thorough drying the air is sometimes finally bubbled through sulphuric acid. In this case H2SO4 must also be used as the absorbent in the place of the two calcium chloride tubes (Fig. 12). ELEMENTARY AXALYSIS. 29 chloride tube of the absorption apparatus the water is absorbed, and finally in bubbling through the caustic potash solution of the absorption bulbs the carbon dioxide is removed; the slight amount of moisture picked up here is removed by the straight calcium chloride tube (sec fg. 12). The details of the method are given in the following experiment. Fig. 13. Experiment. Combustion analysis of salicylic acid. The combustion-tube has been charged 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, finally poui" 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 which has stood in a desiccator several days. Through a clean short-stemmed funnel pour the salicylic acid into the mixing-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 the CuO into the mixing-tube. When the tube is half full, insert the stopper; hold the tube and stopper firmly and shake very vigorously. "Wlien weU mixed, quickly empty the contents into the combustion-tube; rinse the mixing-tube by shaking successively with small portions of fine oxide until all the oxide has been trans- ferred to the combustion-tube. Replace the spiral and 30 ORGANIC CHEMISTRY. pour in the coarse oxide. Replace the stopper and con- nect with the air-purifying apparatus and start the air stream. The CaCl2 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. Start one burner at a time and with the lowest flame possible, then very gradually increase the flames in number and size. Do not heat the fine oxide at all. In the meantime weigh the cal- cium chloride absorption-tube and the caustic potash bulb wilh its calcium chloride tube (remove the plvgs before weighing\ When the coarse oxide has been brouglit to a dull rod heat, the part of the tube which contains this having been covered with tiles, attach the absorption apparatus in place of the ordinary calcium chloride tube. Now start the heating of the other end of the tube, containing the fine oxide and. the substance, very gradually, beginning at the far end. 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. Finally, bring the whole tube to a dull red heat (never hotter). After thirty minutes (one hour if air is used) at this temperature begin to cool the tube by gradually turning down the burners from each end. 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 ELEMENTARY ANALYSIS. 31 rapidly to sweep out of the tube all water-vapour 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 apparatus. 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 cliloride 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 H2O produced X 100 9Xwt. of substance burned" The increase in weight of the potash bulb and straight calcium chloride tube is equal to the weight of the car- bon dioxide produced. Carbon represents y^y of this, therefore for calculating the per cent of carbon the formula used is: wt. of CO2 produced X3X100 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 nitrogen may be formed when the substance is oxidized as above. This necessitates a special modification of the 32 ORGANIC CHEMISTRY. 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,! 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 off; when combustion is complete the air stream is again turned on to remove all the products from the tube. 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 ' By this treatment any oxide adherent to the copper yields up its oxygen to oxidize the. alcohol to aldehyde. ELEMENTARY ANALYSIS. 33 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 combustion is completed carbon dioxide is passed again until the tube is cleared of nitrogen, as shown by the volume of the gas in the burette remaining constant. The caustic potash absorbs all the products of combustion except nitrogen. The jurette is allowed to stand for an hour to come to room temperature, the alkah being levelled 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 centimeters of gas is read off. The temperature of the nitrogen is found by placing a thermometer against the burette, with the bulb at the mid-level of the gas. The barometric reading (corrected for tem- perature) 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 corresponding to 1 c.c. of the moist gas in the burette, at various temperatures and under various pressures (see Appendix, p. 405). In order to use Fig. 14. 34 ORGANIC CHEMISTRY. the table for nitrogen collected over alkali, add to the barometric pressure the difference between the vapour pressure of water and that of 40% potassium hydroxide at the temperature of observation (see table VI, p. 408). 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 pro- duced 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. Kjeldahl's method is extensively employed in bio- chemical analysis and will be found fully described in many of the laboratory manuals on that subject. // 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 them passing into the absorption tubes, where they would be absorbed. When sulphur is present lead chromatc takes the place of the cupric oxide in the tube, lead sulphate being formed during combustion. Having determined the percentage composition, 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 i), and make use of these smaller figures, or the 1 In many cases some other common divisor will have to be used. ELEMENTARY AXA^YSIS. 35 nearest whole number, to express the number of atoms of each element in one molecule. An example will illustrate this. Alcohol was found by one analysis to contain 52.05% C, 13.13% H, and 34.82% 0. Then 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 C2H6O. The same per- centage composition would, however, be shown by any substance having the formula C2„H6nO„. 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. CHAPTER IV. MOLECULAR WEIGHT PETERMINATION. THE NA- TURE OF SOLUTIONS. OSMOTIC PRESSURE. IONIZATION. COLLOIDAL SOLUTIONS. SURFACE TENSION. VISCOSITY. 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 cardinal points in physical chemistry which relate to these subjects. As we shall see later, gases and solutions in their physico-chemical behaviour are very much alike, so that a clear conception of the gas laws, which are well known and readily tested, will enable us to study more satisfactorily 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 ^|^ of its volume at 0° for each degree of rise of temperature. Thus a gas occupying a volume of 1 litre at 0° will occupy 2 litres at 273°, if the pressure remaims constant. In making calculations it should be remembered that the absolute temperature of 0° is 273°, and therefore for any temperature above 0° the absolute temperature is that temperature plus 273°. Another way of stating the law is that the volume of a gas (at constant pres- sure) varies directly with its absolute temperature. 36 MOLECULAR WEIGHT DETERMINATIOX. 37 2. Boyle's law: provided the temperature remains constant, the vokime of a gas varies inversely as the pressure. Thus, if 1 litre of gas be compressed into the space of 0.5 litre, the pressure has been doubled. 3. Avogadro's hypothesis: under the same conditions of temperature and pressure, equal volumes of all gases contain the same number of molecules. THE MOLECULAR WEIGHT OF GASES AND VAPOURS. 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 molec- ular weights of other gases can readily be ascer- tained. 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 molecu- lar weight of 32, being sixteen times heavier than hydrogen. Two grami of hydrcgen at 0° and 760 mm. Hg pressure has a volume of 22.4 litres. 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 wiU also occupy a volume of 22.4 litres (at 0° and 760 mm.).. Such a weight in grams corresponding to the figures for the molecular weight is called a gram-mohcule or a jnol. In consequence of Boyle's law it must follow that if we compress a mol of any gas at 0° to the volume of 1 litre it will have a pressure of 22.4 atmospheres (i.e.^ 22.4X760 mm. Hg). 38 ORGANIC CHEMISTRY. 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 molecular weight. As an example, suppose that 0.2 gm. of a dry gas has a volume of 50 c.c. at 10° and 740 mm. Hg; what is the molecular weight? 27S 740 50 X „^., , ..^ Xr^- 46.899 = c.c. at 0° and 760 mm. 273 + 10 760 But a mol occupies 22400 c.c. Then 0.2 gm. is 46 899 - ".., of a mol, therefore the mol is 95.4 gm. The 22400 molecular weight is 95.4. Vapours obey the same laws as gases. Substances, solid or liquid, which can be vaporized by heat submit to a molecular weight determination as readily as gases. In practice the determination is made either by weigh- ing a known volume of the substance in the form of vapour, or by measuring the volume of the vapour produced from a known weight of the substance. A known volume of vapour 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 tem- perature 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 determined, and from these data the molecular weight MOLECULAR WEIGHT DETERMINATION. 39 can be calculated. This method, while simple in principle, is nevertheless tedious in practice. A much more useful method for general purposes is that of Victor Meyer, in which the volume of a known weight of vapour is ascertained by finding how much air is displaced in a closed apparatus when the sub- stance changes to a vapour. The apparatus,^ as shown in the figure, consists of an elongated bulb con! inued above into a long neck closed at the top by a rub- ber 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 which contains some liquid with a boiling-point 40°-50° above the vaporization temperature of the substance. ExPEBiMENT. Fill the bulb of the outer tube two thirds fuU of distilled water; suspend the inner tube ' Aa 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. Fig. 15. 4(1 ORGANIC CHEMISTRY. 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 ako hang a thermometer in the steam-cham- ber and insert a bent glass tube as a steam-\^ent. Now boil the water (start the heating ve. y gradually). When the thermometer registers a constant temperature, i.e., the boiling-point of the water,i 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, see fig. 15) a little sealed glass bulb con- taining a known weight of pure chloroform (the bulb having been weighed before and after filling). Fit the stopper tightly, and wait a few minutes to deter- mine 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 burette or one specially inserted in the rubber tubing connection). Then close the cock, so that the burette communicates 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°. MOLECULAR WEIGHT DETERMINATION. 41 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 10-15 minutes, dose the cock of the burette. Measure the volume of the air displaced into the burette in exactly the same way as in nitrogen estimations (see p. 33), correcting for temperatm-e, also for aqueous (see Appendix) and barometric pressure, and convert to the volume at 0° and 760 mm. (see p. 38). To make the calculation divide 22400 (22.4 L.) by the number of cubic centimetres 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 substance, 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 gas by mieans of a manometer, but it is obviously 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 container. In the case of a gas the molecules are suspended in a vacuum; in the case of a solution they 42 ORGANIC CHEMISTRY. are suspendetl in a solvent; the solvent of a solution is, therefore, analogous to the vacuum in which the gaseous molecules are suspended. For purposes of analogy is there any means by which the pressure of one gas suspended in another gas may be determined? The metal palladium when heated to 200° allows hydrogen, but no other gas, to diffuse through it. If, therefore, a small vessel of heated palladium containing nitrogen be suspended in a confined atmosphere of hydrogen, the latter being kept under constant pressure, hydro- gen will diffuse into the vessel but no nitrogen will diffuse out. In consequence of this the pres- sure inside the palladium vessel will become greater than that outside, and the difference between the two at the end of the experi- ment will represent the pressure of the nitrogen. The figure shows a piston working freely in the palla- dium box; hydrogen passing into the nitrogen chamber (indicated by arrows) increases the pressure on the under surface of the piston so that the latter moves upward. This gives us an indication of how it may be possible to measure the pressure of a dissolved substance, for in the above experiment we can conceive of the nitrogen as being in solution in hydrogen; indeed, to make the case still plainer, we can start the above experiment with a mixture of hydrogen and nitrogen inside the palladium vessel and measure increase of pressure, The hydrogen Fig. 1G. OSMOTIC PRESSURE. 43 really dissolves in the palladium membrane, and is given off on the other side where the partial pressure of hydrogen is low. This experiment shows us that if we could but obtain a membrane allowing only one of the constituents of a solution (i.e., the solvent) to pass through it, then we could measure the pressure which the other constituent (i.e., the solute) exercises. An example of such a membrane is a film of copper ferrocyanide. Since this film of copper ferrocyanide is too fragile to exist unsupported, it may be deposited in the pores of a porous cell (such as is used for electric batteries), and the following method may be used in preparing 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 con- necting with a suction-pump. The cell is placed in water, and the water is sucked through the pores; then in acid, then in water again. By this means the pores of the cell are thoroughly cleaned. When clean, the cell is placed in a 15 per cent solution of potassium ferrocyanide, 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 immersed for several hours in a 25 per cent solution of copper sulphate. The copper sulphate reacts with the potassium ferrocyanide in the pores of the porous pot, so that a fine precipitate of copper ferrocyanide is deposited. After washing in water the cell is ready for use. If a solution of cane sugar be placed inside such a cell and this be suspended in water, the latter will pass 44 ORGANIC CHEMISTRY. into the cell and cause the A'olume of fluid in this to in- crease, so that, if a vertical glass tube be connected with the cell, fluid will mount up in it to a very considerable height; or if we connect a pressure-gauge (manometer) with the cell, we shall be able to measure the pressui-e instead of the increase of volume. If a gram-molecu lar 1 (more accurately, weight normal) solution of cane sugar ber employed, the pressure in the cell as recorded by the mercury manometer comes to be equal to that of 22.4 atmospheres. This pressure, however, can seldom be attained, for it is too great for the fine film of copper ferrocyanide to withstand.^ The film of copper ferrocyanide ruptures, and an escape of the fluid takes place. The pressure thus demonstrated is called osmotic pressure, and a membrane of the nature described is called a semi-penneahle membrane? None of the membranes used for this purpose are perfect semi-permeable membranes, for traces of solute can pass through them. Some membranes, such as porous plates the spaces of which have been partially blocked by fine non-gelatinous precipitates so that the capillary pores are about O.Six ' By grain-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 (Arrhenius), while by weight normal is meant a solution in which the gram-molecular weight of substance is dissolved in 1000 gm. of solvent. ^ An actual pressure eqiial to 22.4 atmospheres has recently been observed by Morse and Frazer by using a specially con structed apparatus. ' Solutions of salts and other substances which become dis- sociated in solution do not behave according to this law (see p. 57). OSMOTIC PRESSURE. 45. in diameter, have a sieve-like action in developing osmotic pressure, holding back the larger molecules and letting water pass through. In some other cases there is involved the question of solubility of a sub- stance in a membrane (cf. palladium experiment), for instance if a membrane well soaked with water be interposed between moist ether and a mixture of benzene and ether, ether will dissolve in the membrane and pass over into the benzene, but benzene will not pass through into the ether. It has been found that the osmotic pressure of all gram-molecular solutions corresponds to a pressure of 22.4 atmospheres, which, it will be remembered, is the pressure of a gram-molecule of gas compressed to the volume of a litre. Knowing this, we can calculate what the pressure of any dissolved substance in solu- tion will be. Thus, the pressure a; of a 1 per cent solution of cane sugar may be calculated from the proportion: Molecular solution : 22.4 atmospheres:: 1% solution: x. Solutions which obey the laws of osmotic pressure most accurately are those of the strength of decinormal solutions. These facts show us that the osmotic pressure of a solution must be analogous to the pressure of a gas; the volume in both cases being easily measured, we are therefore in a position to test the gas laws in solutions. 1.' According to Gay-Lussac's law, the osmotic pres- sure should be proportional to the absolute temperatm-e. That this is so is proved by the following observation. A 1 per cent solution of cane sugar at 14.2° has an osmolis pressure of 510 mm. Hg, and at 32° of 544 mm. 46 ORGANIC CHEMISTRY. Hg. According to calculation it should be 540.6 mm. Hg (practically agreeing with the finding), thus 2. According to Boyle's law, the osmotic pressure should be directly proportional to the concentration of the solution — or, in other words, inversely proportional to the A'olume of the solution. By comparing the osmotic pressures of cane sugar solutions of varying strengths (at the same temperature), the following values have been obtained : Gram-molecules in Osmotic Pressure 1000 gm. Water. in Atmospheres. 0.1 2.35 0.2 4.70 0.6 14.09 1.0 23.49 It will be seen that the law applies. 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 solution bear the same ratio to one another as the molecular weights of those substances) ought to have the same osmotic pres- sure. As already stated, this has been found to be the case. OSMOTIC PRESSURE. 47 Theoretically, the measurement of the osmotic pres- sm-e would be a simple enough way of determining the molecular weight, but, in practice, the method can- not be used, because, unless elaborate precautions be taken, any considerable pressure in the cell mechanically ruptures the membrane, and so allows the fluid to leak and the pressure to fall. The method is of interest mainly because it shows us the striking analogy between a gas and a solution. It shows us that the osmotic pressm-e is virtually the same as the gaseous pressure which anjr substance would exert were it present as a gas in the same volume as that occupied by the pm-e solvent: that if the solvent were suddenly removed the dissolved molecules might be considered as remain- ing suspended as a gas and the gas would be under a pressure corresponding to its volume. Considerable discussion and criticism of the present ^^ews as to the nature of osmotic pressure has recently been brought forward. Biol::gical Meth?ds for Mrasuring Osmotic Pressure. If, in the above 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 one another bv a semi-permeable membrane.' ' This is true only for solutions of dififusible substances in the same solvent (water). 48 ORGANIC CHEMISTRY. 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 employ 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.' 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 iso-osmotic 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 wiU difi^use 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 wiU 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 hajmatocrit. This consists of a graduated narrow capillary tube, about seven centimetres 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, accurately fitting, metal plates held in position by a spring. • The corpuscles are, however, permeable for alcohols, free acids, and alkalies, ammonium salts and urea. MOLECULAR WEIGHT DETERMINATIOX. 49 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 whose molecular concentration 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. K the column of corpuscles be shorter, the solution is hypertonic. Iso-osmotic solutions are isotonic to the same cells. Solutions of corresponding concentration (as, one- tenth gram-molecular) of most organic compounds (except metallic salts, acids and bases) are iso-osmotic; solutions of ionizable substances (p. 57) have a greater osmotic pressure than solutions of other substances; a comparison is made in the following: Cane sugar 1 . 00 Potassium nitrate 1 . 67 Sodium chloride 1 - 69 Calcium chloride 2 . 40 These figures are the isotonic coefficients of the substances. 50 ORGANIC CHEMISTRY. 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 hypertonic 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 solu- tion (3%) does not swell up, the epithelial cells are not noticeably permeable to water passing in. Experiments. (1) Osmotic Pressure Effects in a Vegetable Membrane. Shave very thin slices from a red beet, mount some on a slide with very little water, and examine microscopically. Now drop a few crystals of NaCl on the slice and observe that the red substance shrinks, the hypertonic solution having caused phs- molysis. (2) Osmetic Pressure Shown by an Animal Membrane. Float an egg in 20% NaCl, the uppermost end contains an air space, open the shell at this point, removing it down to where the egg membrane joins the shell. Stretch a number of strips of parchment paper over the membrane and on to the shell, cementing them to the shell ; shellac the cemented ends. 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 tiie tube and carefully drill a hole through the shell and egg mem- brane. Immerse the egg in distilled water. Aft«r 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 CUSO4, MOLECULAR WEIGHT DETERMINATION. 51 tie a thread about the middle, fasten the thread to a glass rod lying across the top of a 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. (b) Fill the bent portion of a U-tube with melted agar solution, cool, when solidified fill one limb with CUSO4 solution, the other with potassium ferrocyanide solution. On standing several days a sharply definite area of copper ferrocyanide forms midway in the agar. (c) Drop a small lump of CaCl2 into some saturated potassium carbonate solution. On standing a mem- brane develops and grows, making plant-like forms. MOLECULAR WEIGHT OF SUBSTANCES IN SOLUTION. Is there then no easily measurable physical property of solutions which depends on their molecular concen- tration, 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 tem- perature at which a solvent freezes is lowered when a substance is dissolved in it, and that the amount of this lowering, or depression of freezing -poinf A, is for dilute ' Cryoscopy is a name given to freezing-point determination. An interesting explanation of the fact that C is quite different for different solvents is furnished in Raoult's extension of his 52 ORGANIC CHEMISTRY. solutions proportional, not, in general, to the rhemical 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 solu- tions in the same solvent must lower the freezing-point to an equal extent. The depression of freezing-point produced by a gram-molecular quantity of a substance dissolved in 1000 gm. of the solvent (weight normal solution) varies for different solvents: Depression of Freezing-point. For water 1 . 86° " benzol 5.00° " phenol 7.20° ' acetic acid 3 . 90° These figures are called the constants (or C) of the solvents. They correspond, therefore, to an osmotic pressure of 22.4 atmospheres. The apparatus in which the freezing-point determina- tions are made is known as Beckmann's. This consists of a large test-tube, to contain the substance, suspended law: if a gram-molecule of a compound be dissolved in 100 gram-molecules of solvent (except water), the freezing-point of the latter will be depressed by about 0.62°. MOLECULAR WEIGHT DETERMIXATION. 53 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-mix- ture is stirred with a loop of wire as represented in the diagram. In the inner test-tube is suspend- ed the bulb of a Beckmaim ther- mometer. This thermometer does not give absolute- 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 modi- fications it may be used to tell the different temperatures at which two solutions boU. Before usmg the thermometer for freezing- point demonstrations 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 mercury at the top of the reservoir, which is connected with the upper end Fig. 17. 54 ORGANIC CHEMISTRY. of the thermometer tube, to fall to the bottom and so to become discomiected from the mercmy column in the thermometer tube. Should the meniscus of mer- cury stand below the scale at the 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 determination the irmer tube of the apparatus is partly filled with the solution under examination so that the latter comes a little above the bulb of the thermometer (see fig. 17). The tube is then placed directly in the freezing-mixture until the mercury, having fallen ta its lowest level, be- gins to rise again, after which the tube is removed 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 when- ever constant and compared with the reading obtained when pure water (or whatever other solvent is used) is frozen. This difference is designated by J} ' 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, therefore, 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 4°, that of the solution at 2°, and the point of supercooling at 0°. A is 2, then 2 X .0125 = .025 ; 2°-!- .025 =2.025°; 4° -2.025 = 1.975° =corrected A. MOLECULAR WEIGHT DETERMINATION: 55 Since this constancy of C, 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. ExPEEiMENT. 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 gm. of dis- tilled water. Compare the freezing-point of this solu- tion, corrected for supercooling, with that of pure water. It will be found to freeze almost exactly at 1.86 " lower than that of water. In determining the molecular weight of any sub- stance 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 imder examination. Knowing what C for our solvent is, — in other words, through how many degrees centigrade 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 pro- portional to the difference from C recorded by the thermometer. In other words, the depression ob- served, represented by J, is to C as the strength of /weight of sub stance ^ . ., . , the solution used ( weight of solvent ) '' *° *^^* °^ ^ gram-molecular solution (or rather a solution containing a gram-molecule diesolved in 1000 gm. of solvent, see foot-note, p. 44). 56 ORGANIC CHEMISTRY. s c m = yX7, where S equals the weight of substance used in grams; L, the weight of solvent in grams, j^, when solved, gives a decimal fraction expressing what part of 1 gm. of the substance is dissolved in 1 gm. of solvent; therefore, to calculate the gram-molecule (the amount dissolved in 1000 gm. of solvent), m must be multiplied by 1000, and M equals the molecular S C weight in the equation M=-jXjX 1000. For example, let us take a determination on a one per cent cane-sugar solution, the J is about 0.054.° The molecular weight of the sugar, therefore, is, -j^X-^X 1000 =344. According to the formula, C12H22O11, it should be 342. The A of blood and of urin? 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 sub- stances, even though they be readily soluble in the above-mentioned solvents. This is on account of the fact that in the case of those the extent to which a gram-molecular quantity per 1000 gm. of solvent lowers the freezing-point is greater than C. Practi- cally all metallic salts and most acids and bases when in aqueous solution are included in this category. To demonstrate this let us determine the depression of freezing-point produced by a gram-molecular solution of sodium chloride. IONIZATION. 57 Experiment. Weigh out one-tenth (one-twentieth is better) the molecular weight of pure sodium chloride in grams and dissolve, as in the 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 J for a gram-molecular solution, it is easy to calculate how many gram-molecules per litre {X) a J of 3.35 will represent, thus: 1.86 :1 ::3.35:.Y; Z =1.8. To ascertain the actual osmotic pressure of the sodium chloride solution we must accordingly multiply 2'2A atmospheres by 1.8. This gives us about 40 atmos' pheres. What then is the cause of this deviation from the law? The answer to the question is furnished by comparing the electriml conductivity 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 w^hich conduct electricity appear, from the determination of J, 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 dissociation of molecules into ions takes place that it is possible for the solution to conduct electricity. In fact, our whole 58 ORGANIC CHEMISTRY. conception of the conduction of electricity in solutions is based on this hypothesis. It is supposed that every molecule of substance is charged with positive and negative electricity, which in the intact molecules so neutrahze one another that we do not appreciate either. When these molecules are suspended in solution, how- ever, they show a greater or less tendency to spht up into ions, one set of which carries positive electricity and the other negative electricity. These ions wander about the solution much as if they were independent molecules. When an electrical current is passed through a solution which 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. Ex- amples of anions are oxygen and the acid portion of salts, for example SO4, CI, etc.; the cations include hydrogen and metals. 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 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. IONIZATION. 5q When solutions of acids undergo ionization, the cation H is that which confers the acidic properties to the solution. An un-ionized acid does not act liise an acid; for example, H2SO4 dissolved in toluene does not ionize and will not give off hydrogen in the presence of zinc. (Also see experiment under Picric Acid, p. 307.) 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 usual to designate the various ions by their sym- bols, aflSxed to which is the sign • for cations (e.g., H", Na', etc.) and ' for anions (e.g., CI', NO3', etc.). Some ions must carry two or more units of electrical charge, however, for otherwise in tie case of such a substance as H2SO4 there would be an excess of positive electricity in the molecule. The ion SO4 must therefore carry two charges of negative electricity and be represented by the sign SO4". The valence of the ion usually agrees with the number of unit charges of electricity which it carries. The coefficient of dissociation therefore indicates what proportion of the molecules have become split up into ions. For molecules which can jneld only two ions it cannot be greater than 2, but for those split- ting into more than two ions it may exceed this number. In the concentration of a 1 per cent solution it is 1.82 for KQ, 1.67 for KNO3, 2.11 for K2SO4, 2.18 for NaaCOs, and so on. 60 ORGANIC CHEMISTRY. The amount of dissociation that a salt or acid under- goes in solution depends very largely upon the diUition: the greater the dilution, the greater the dissociation, and therefore the higher the coefficient.^ For example, the coefficient of a 0.27 per cent solution of sodium chloride is 2, as against 1.9 for a 1 per cent solution. In a solution of an electrolyte there is a condition of equilibrium between molecules and ions. The mole- cules are continually dissociating and simultaneously ions are uniting to form molecules. Reactions between electrolytes proceed rapidly, because as fast as ions are used up more molecules ionize in the effort to restore equilibrium. Most organic compounds react slowly because of absence of ions. Experiment. To two test-tubes add a few c.c. AgNOs, to one add NaBr, to the other C2H5Br. Occasionally, when a substance is dissolved, instead of dissociation there occurs a fusion of several of the molecules. In such a case the freezing-point or boil- ing-point method would give too high a molecular weight. This tendency to form complex molecules ,most frequently manifests itself with organic substances containing hydroxyl or cyanogen groups, and when chloroform or benzol is the solvent. Many liquids polymerize, that is, their molecules associate. The condition of water is supposed to be represented by (H20)4. Liquid hydrocyanic acid is (HCN)6. Next in order of association are formic acid 'For example, a solution of 0.073 gm. HCl per litre (.77^,) VoOO/ is completely dissociated. COLLOIDS. 61 and methyl alcohol. The greater the polymerization of the solvent, the greater will be the dissociation of an electrolyte. Experiment. Add a few drops of phenolphthalein solution to 25 c.c. of neutral ethyl alcohol, then one drop of concentrated NH4OH, no colour change; dilute with water, and a pink colour develops because ioniza- tion of the hydroxide takes place in the dilute alcohol. COLLOIDS. Substances may be distributed or dispersed in a liquid in various ways. Insoluble substances in the form of a coarse powder when shaken, with a liquid are momentarily suspended in the liquid but quickly settle out, while very fine powders may remain sus- pended a considerable time. As the size of the particles is decreased, the time that they remain in suspension is increased, until a stage is reached at which the par- ticles do not settle. Mercuric sulphide may be pre- pared by passing hydrogen sulphide into a neutral solution of mercuric chloride; no precipitation occurs; to the eye it seems a perfectly uniform solution. Under the microscope, however, the liquid is seen to be full of small particles in active motion (Brownian). Such an apparent solution is classed not as a suspension but as a susPENsoiD. In the case of most suspensoids, the particles are too small to be seen with the microscope. Not only may solid particles be suspended in a liquid, but liquids also may be suspended in liquids as minute droplets. For example, if an oil be shaken very vigorously with water, the oil is broken up into drops 02 ORGANIC CHEMISTRY. which remain suspended for a moment. If the oil be treated with an emulsifying agent and then mixed with water, the oil is present as microscopically fine drops, each drop being covered with a film of the emulsifying material. Such an emulsion remains apparently homo- geneous for some time. There are certain complex organic substances which in solution are believed to be present in the liquid phase as film-covered droplets, which are infinitely smaller than emulsion drops. Such substances are called EMOLSOiDS. Thus emulsoids differ from suspensoids in that the former are in the liquid phase. Other substances dissolve, forming what we call true solutions, which we conceive to be liquids having molecules of the solute uniformly distributed through- out the solvent. However, it has been shown in the case of some solutions that the centrifuge can cause them to become non-homogeneous, the solution becoming more concentrated at the bottom of the tube. It would, therefore, be better to ftall such solutions molec- ular disperse solutions. The finest particles of sus- pensoids and emulsoids are not separate molecules, but agglomerations of molecules. Thus there is a regular gradation in dispersion mix- tures from molecular dispersoids to emulsoids and sus- pensoids and then to emulsions and suspensions. The diameter of the particles is said to be as follows: Molecular dispersoids: 0.1-l.OfifiA Emulsoids [ 10-01 Suspensoids ) ' ^~ ' ^' Suspensions and emulsions: greater than 0.1 fi. » A jAn is one millionth part of a millimeter. A (j. is one thou- sandth part of a millimeter. COLLOIDS. 63 As a rule suspensoid particles are much larger than emulsoid particles, in the case of colloidal gold, however, some particles as small as 3-10///I have been obtained. Emulsoids and suspensoids are classed together as colloids. An approximate idea of the size of the particles can be obtained by graded filters, the size of their pores being known. By this method colloidal Prussian blue is shown to have the largest particles and dextrin the smallest. The following list gives in order some of the sub- stances having particles intermediate in size: Prussian blue. Colloidal ferric hydroxide. Casein (in milk). 1 per cent gelatin. 1 per cent haemoglobin. Serum albumin. Albumoses. Dextrin. The rate of diffusion of colloidal substances is very slow compared with that of non-colloidal substances; for instance, it takes egg albumin 21 times as long as it does sodium chloride to diffuse to the same extent, and caramel 42 times as long. Colloids will not diffuse through a gelatinous partition such as an animal mem- brane or parchment paper, whereas crystalloids readily diffuse (diffusion through a membrane is called osmose^). Therefore colloids and crystalloids can be separated 1 Do not confuse osmose with osmptic pressure phenomena. 64 ORGANIC CHEMISTRY. from one another by dialysis (see p. 19). Some colloidal solutions have been shown to exert osmotic pressure. A 1% haemoglobin solution gave 3.5-4.35 mm. (Hg) pressure, while a 10% gelatin solution at 26° gave 70 mm. pressure which was remarkably con- stant for a long time. In these experiments a dialyzing membrane was the osmotic membrane, so that the effect of diffusible impurities was eliminated. Ap- parently the colloidal particle exerts the same effect in causing osmotic pressure as a molecule of a crystal- loid. The number of molecules aggregated together into a colloidal agglomerate is variable and may be different at different times in the same solution. When- ever the colloidal clumps become larger the osmotic pressure is lessened. Because of this variabiHty it is obviously impossible to determine molecular weight by the usual methods. Depression of freezing-point is valueless for the pur- pose, even aside from the question of variable aggrega- tion, because a solution which has an osmotic pressure of 50 mm. gives only 0.005° depression of freezing-point. Evidence of the presence of colloidal clumps in a solu- tion can be obtained with the aid of the ultra-microscope. A powerful beam of light is passed into the solution, the axis of the microscope being at right angles to the ray. The particles divert or reflect the hght. This is on the same principle as the Tyndail phenomenon observed in the scattering ot hght by dust particles in the air when a sunbeam passes into a room. What is seen in the colloidal solution by means of the microscope are bright moving specks on a dim background or else a haze of hght. COLLOIDS. 65 In the case of suspensoids the size of the clumps can be estimated by means of this apparatus. One speci- men of colloidal gold solution has been prepared having particles too small to be distinguished. Solutions of emulsoids which have been dialyzed until electrolytes have been removed probably have particles less than 20/1/1 in diameter; they cannot be distinguished. These show the haze of Hght. Extreme dilution is necessary to cause sufficient separation of the clumps of any colloidal solution from one another to make them distinguishable. In the presence of electrolytes, particularly salts, colloids aggregate into larger clumps; under these circumstances even emulsoid particles can be detected. Thus the digestion of protein by pepsm, it is said, can be watched with the ultra-microscope (HCl present). Colloidal solutions can be prepared that are optically negative to the ultra-microscope, while, on the other hand, solutions of some crystalloids, as sucrose, cannot be obtained which are optically negative. Apparently, it is safest to consider all solutions as being ultimately non-homogenous. It is probable that the motion of colloidal particles is due to the same force as causes the movement of molecules and of ions. This motion and also the bump- ing of the colloidal particles by the rapidly moving ions greatly favor the agglutination of the particles to form larger masses. Ldntner's soluble starch in 0.01% solution gives a faint diffuse polarized light^cone. A 0.01% gelatin solution shows tiny whitish particles, barely visible, and freely moving; if the solution is prepared by boil- ing, individual particles cannot be seen, but only a light- 66 ORGANIC CHEMISTRY. cone. A 0.07% solution of specially purified glycogen showed numerous extremely small white particles (in motion). If various proportions of alcohol are present in different portions of a glycogen solution, the particles become easily observable, the size of the clumps increas- ing steadily with increase in alcohol concentration. Solutions of suspensoids do not gelatinize, are not viscid, and are coagulated by a small quantity of elec- trolytes. They are irreversible colloids, that is, after being precipitated they cannot be put into colloidal solution again. 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 ferro- cyanide, 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, no 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 stand- ing a blue precipitate forms. Save the more con- centrated Prussian blue solution for a later experiment. Even suspensions of some fine powders, as lamp- black or kaolin, are precipitated by electrolytes in a similar manner to suspensoids. The power of elec- trolytes to precipitate suspensoids is proportional to the electrical conductivity of the electrolyte in the solution. A 0.7 gram-molecular solution of acetic acid and a 0.0038 gram-molecular solution of hydro- chloric acid have the same precipitating power toward COLLOIDS. 67 colloidal arsenious sulphide, and have practically the same conductivity (therefore the same // ion con- centration). Some colloids are electro-positive while others are electro-negative; that is, when an electrical current is passed through the solution the particles travel to the cathode or to the anode respectively. Suspensoids are precipitated by ions of opposite electrical sign; electropositive colloids, as ferric hydroxide, are pre- cipitated by anions, as CI, SO4, while electronegative colloids, as arsenious sulphide, are precipitated by cations, as H, K, Mg. The colloidal particles attract ions carrying an opposite electrical charge; their elec- trical charge is thus neutralized. In consequence the surface tension between the particles and the water becomes greater. This leads to agglomeration of the colloidal clumps, progressing steadily until the masses are large enough to separate out as a precipitate. Suspensoids of opposite electrical sign will mutually precipitate one another, as illustr?.ted by the experiment. ExPEBiMENT. To 5 c.c. of coUoidal arsenious sul- phide solution add gradually colloidal ferric hydroxide solution, while shaking, until a precipitate forms. Emulsoid solutions are viscid, they tend to gelatinize, and are not coagulated by small amounts of electrolytes. They are reversible, that is, after being precipitated by strong solutions of salts or by alcohol, etc., the pre- cipitate can be redissolved in water. Experiment. Reversible colloids. Pour about 5 c.c. of warm 5% gelatin solution into a test-tube. Shake 68 ORGANIC CHEMISTRY. well; the froth indicates viscidity. Cool the tube with running tap water; the solution becomes a jelly. Warm again until fluid, add an equal volume of magne- sium chloride solution; no precipitation occurs. An aqueous colloidal solution in the liquid state is called a hydrosol, in the gelatinized state a hydrogel. Suspensoids cannot travel into an emulsoid solution when the latter is in the gel state, while crystalloids readily diffuse into the gel. 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. concen- trated copper sulphate solution add ammonia water until the precipitate is just redissolved) . Let the tubes stand an hour or more; the Cu solution penetrates the agar, while the colloidal suspension does not. At the end of the session empty the tubes, leaving the agar in, rinse out, note the condition of the agar. Some emulsoids are not colloidal when dissolved in a solvent other than water; for example, tannic acid dissolved in glacial acetic acid is a molecular dispersoid, but in water it is a colloid. Emulsoids require a high concentration of salts to effect precipitation from a solution. This action is not an ion effect concerned with electrical charges as in the case of suspensoids, but is a salting-out process. Specially purified serum protein was found to be neither electropositive nor electronegative, yet it was precipitated by salts from neutral solution. SURFACE TENSION. 69 When an emulsoid is added to a suspensoid solution it exerts a protective action, preventing or hindering the precipitation of the suspensoid by electrolytes. 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 obtained. (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 same rate into a beaker. An opalescent solution (milky) which resembles gly- cogen solution, but no precipitate, is obtained. Now dilute and note carefully absence of precipitate. Photographic plates are made by taking advantage of the protective action of gelatin, preventing pre- cipitation of the sUver salt. The therapeutic agent, collargol, is said to be a col- loidal sUver 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. There is good reason for beheving that enzymes are colloidal substances. SURFACE TENSION. The molecules of a liquid are attracted to one another in all directions, these attractions neutraKzing one another. At the surface, however, the molecules are attracted towards the middle of the liquid and there is no counter-balancing attraction in the opposite 70 ORGANIC CHEMISTRY. direcf^ion, thus there results a definite pressure called surface tension. In the case of solutions there is a greater concentration of the solute at the surface than elsewhere. The pressure crowds the molecules closer together. Surface tension is equivalent, then, to the stretching of an elastic membrane at the surface. Fine powders of such a nature that they do not readily take up moisture (as sulphur) float when sprinkled on water — the particles rest on the surface exactly the same as if on a membrane. If the surface tension be lowered as results when bile salts are dissolved in the water, such particles will not be buoyed up, but will sink. Many organic liquids such as methyl and ethyl alcohols, ether, chloroform, glycerol, acetone, anihne, pyridine, phenol and many 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. Experiment, (a) Fill a test-tube with water, another with 1% solution of castile soap; on the surface of each liquid dust a few very fine particles of sulphur. The sulphur readily sinks in the soap solu- tion. Dilutions of the soap may be made to find how dilute a solution still shows marked lowering of surface tension. (6) Dip capillary tubes in various liquids, as water, alcohol, soap solution, etc. The height to which the liquid rises (more accurately the weight of hquid raised) is a measure of the surface tension. In similar manner within a liquid containing colloidal or suspended particles, there is a surface of the liquid SURFACE TENSION. 71 presented to the surface of each particle and hence surface tension comes into play. Thus in the region of each colloidal particle there is a minute surface tension area surrounding it. How important this is in a consideration of colloidal solutions will be under- stood by calling attention to the enormous increase of surface exposure when a. substance 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 largest suspensoid particles (0.1[i.), will acquire a surface area of 314 sq.cm. If a col- loidal solution be purified, that is, freed of other dis- solved substances, the surface tension about the par- ticles becomes higher, and as it becomes higher, the difference in potential increases and the particles divide into smaller particles. When an electrolyte is added to the solution, it concentrates at the surfaces between solvent and colloidal clumps, just as it concentrates at the surface in contact wi th air (as above) . The electrical charge of the electrolyte opposes the force of surface tension and lessens it. Surface tension being lessened the colloidal particles aggregate more and more so as to restore the balance in potential. Suspensoid particles attract ions of opposite electrical charge and hold them, so that when the colloid is precipitated the ions are carried down also. This holding is not chemical union, but condensation of a substance at the surfaces of contact and is called adsorption. So also two colloids of opposite electrical charge will hold one another by adsorption and pre- cipitate together. One of the colloids may be an emul- 72 ORGANIC CHEMISTRY. soid; the suspensoid and emulsoid adsorb and then when an electxolyte is added the suspensoid is pre- cipitated, and the adsorbed emulsoid is carried down with it. For example if Fe(0H)3 (electropositive) be mixed with a faintly alkaline solution of protein (electronegative), on adding a salt both iron and pro- tein 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 (Merck's dialyzed iron containing 5% FeaOs), shake, add powdered sodium sulphate, shaking after each addition, until a gelatinous precipitate forms. Filter, test the filtrate for protein (biuret test, p. 228). Adsorption can occur independently of electrical considerations. In this case it is to be explained solely by the concentration of the adsorbable substance at colloidal surfaces and the lowering of surface tension of the liquid about the colloidal particles. The use of animal charcoal to remove coloring mat- ters and certain other substances from solutions is a' case of adsorption. Ferments readily adsorb to colloids. There is a surface condensation of the enzyme on the colloid particles. This is not selective, for an enzyme can adsorb to substances on which it has no action. Recent investigation seems to show that the rate of enzyme action at any particular moment is propor- tional to the amount of enzyme present in the adsorbed state at that moment. VISCOSITY. 73 VISCOSITY. The viscosity of a liquid depends upon its internal friction. 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 comparing , with the time required by an equal volume of water in the same apparatus. For accurate work the tem- perature must be carefully regulated. We may suppose that the layer of liquid in contact 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 centre 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 measure- ment of this rate gives a basis for calculating vis- cosity. AMien liquid particles push past each other in this way work must be done and the amoimt 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 which has been chosen as a standard. Comparing with water .as unity the specific viscosity, (at 25°) of five per cent ethyl alcohol is 1.161 and of five per cent ethyl acetate is 1.044. Experiments. (1) Compare the viscosity of water, of absolute alcohol and of 50% alcohol successively in an Ostwald viscosity pipette. To do this pour about 5 clc. 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, dis- connect and prevent the liquid flowing back by sealing the end with the finger (as in using a pipette)-, draw 74 ORGANIC CHEMISTRY. off the excess of liquid in the large tube with a pipette. 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. The dilute alcohol has a greater viscosity than either water or absolute alcohol. (2) Use a viscosimeter 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, repeat the experiment, using a temperature 20° higher. Each determination is made as follows; put 200 c.c. of the hquid 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 specific viscosity of the oil. Suspensoid colloidal solutions have a viscosity but shghtly different than it would be if the colloidal particles were not present. Emulsoid colloidal solu- tions, however, show marked increase of viscosity if their concentration is above one per cent. Traces of acid or of alkali distinctly increase the viscosity of some emulsoids. There is a point of max- imum viscosity, for example with gelatine solution N the maximum viscosity with HCl is secured when ^^ is present. A concentration of alcohol below that necessary to cause precipitation (as 35%) increases the viscosity of albumin solutions. Increase of temperature lessens viscosity. MOLECULAR WEIGHT DETERMINATION. 75 MOLECULAR WEIGHT DETERMINATION BY ANALYSIS OF DERIVATIVES. The molecular weight of a substance can also be deduced from a quantitative analysis of its deriva- tives. This method is most easily apphed to acids and bases. Take, for example, a simple acid, such as acetic. By analysis, its formula might be CH2O, 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 107 9 CHOAg, then the % of Ag must be jgg^Xl00=78.8. Obviously CH>0 cannot be the correct formula for acetic acid. If we take C2H302Ag as the formula, 107 9 the per cent of silver will be j^^X 100 =64.6%, therefore C2H4O2 is the correct formula. In the case of bases, their chlorplatinates have been found to be the most suitable compounds to form for this purpose. CHAPTER V. FORMULA, EMPIRICAL AND STRUCTURAL. ISOMERISM. A KNOWLBDGE 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 num- ber 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 C9H10O3. 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 ascer- tained 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 group.s to unite together, i.e., by synthesizing the sub- 76 FORMULAE, EMPIRICAL AND STRUCTURAL. 77 stance. If the synthesis is successful, the structure of the molecule is proven. 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 substance, but it is also an epitome of the more important reactions of the substance. In the chapters which immediately follow this one, the methods by which the various facts indicating the structure of the molecule are discovered wiU be fully explained (see especially acetic acid, p. 140). When we come to study the more complex substances, we shall find that even the structural formula does not always suffice to differentiate the substance, 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 de- scribed in coimection with lactic and tartaric acids (pp. 198 and 206). Before starting with a systematic study of the com- poimds 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 imderstanding why it is so written. If he conscien- tiously follows this advice, he will soon find that organic chemistry is by no means the uninteresting and discon- nected subject so many students think it to be. 78 ORGANIC CHEMISTRY. SYNOPSIS OF CHAPTERS I-V. Determination of the Chemical Character of an Organic Compoimd. 1. PuRIPICATION. (a) Methods. (6) Tests of purity. 2. Identification. (a) Physical properties. (6) Elementary analysis. 3. Empirical formula. (a) Elementary analysis. (6) Molecular weight determination. 4. Structural formui-a. (a) Reactions to detect , presence and relative placing of atoms and groups of atoms in the molecule. (&) Synthesis of the molecule. 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 re- member the properties and reactions of each organic substance separately, we should utterly fail, and should, moreover, probably overlook one of their most im- portant characteristics in contrast with inorganic substances, viz., their transmutability into other organic compounds. In inorganic chemistry it is im- possible 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 classification 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 CO2, with 79 so ORGANIC CHEMISTRY. sulphur in CS2, etc. We do not, however, consider these as organic compounds, the simplest organic compounds being those in which carbon is combined with hydrogen or with nitrogen. In union with nitrogen, carbon forms cyanogen (CN (in the free state C2N2), which is the lowest member of a group of compounds 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). Practically 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 sub- divide hydrocarbons into several groups. If we express the hydrogen in terftis 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„H2n+2 (3) C„H2n_2 (2) C„H2„ (4) C„H2„_6 (n designating the number of C atoms). 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 behaviour of the members 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; PRELIMINARY SURVEY. 81 indeed, that these directly combine with the reagent by addition, i.e., without chemical substitution. We may, therefore, further subdivide our four groups into two, viz., saturated (1st and 4th) and unsaturated ^ (2d and 3d). Of the two saturated groups it will be found that many members of the 4th group have an aromatic odour, whereas those of the 1st do not. The members of the 4th group are hence often styled aromatic com- pounds, and on account of the fact that the members of the 1st group are very resistant towards 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) .^ Compounds of the first three groups make up the ALIPHATIC or FATTY DIVISION of Organic chemistry. The compounds and derivatives formed by the vari- ous 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 wUl 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. From these preliminary remarks it will be evident that ' Only unsaturated compounds can form addition products. ' The groups are also sometimes named from the lowest member of each, e.g., methane group, benzene group, etc, 82 ORGANIC CHEMISTRY. 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„H2„+2. The following is a list of the most important members: Methane, CH4 Butane, C4H10 Ethane, C2H6 Pentane C5H12 Propane, CsHg Hexane, CeHu It will be noticed that each diiTers from the one preceding it by CH2. They all form the same kind of derivatives, differing from one another again by CH2 ■ thus the hydroxide or alcohol of methane has the formula CH3OH, and of ethane C2H5OH. 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^. 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 H I H— C— H. I H PRELIMINARY SURVEY. 83 When two methane molecules fuse together a hydrogen atom of each disappears and the liberated valence H H I I bonds unite as represented in the formula H — C — C — H. H H Since each of th-e four valence bonds of C has the same value it will b« obvious that only one propane can exist : that we can ^rrite only one structural formula for H H II III it, viz., H — C — C — C— H. But we may have two van- I I I H H H eties of the next member of the series, viz., butane, for, in adding an extra CH3 group to propane, we may add it either to the central C atom of the H I H H— C— H H chain or to one of the end ones. III) H— C C G-H I I I H H H H H H H H — C — C — C — C — H, and the properties of the cor- I I I I H H H H responding body wUl vary accordingly; in other words, it makes a difference when the extra CH3 group is tacked on to a C atom in union with two H atoms (as is the case with the central atom), and when on to one with three H atoms (as in the case of an end atom). 84 ORGANIC CHEMISTRY. When the substitution occurs in the centre of the chain the resulting body is called an iso-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 can be still more clearly demonstrated: thus we may con- sider C as occupying the core of a tetrahedron (made Normal butane Isobutane of wood), the four solid angles of which represent mono- valent combining affinities, these angles being covered in the model by p3T.amidal tin caps representing H atoms (see fig. 22, p. 206). By removing an H cap from two models of methane and joining the two tetrahedra together by the 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 PRELIMINARY SURVEY. 85 model of propane. It does not matter which of the H caps we remove in these manipulations; the resulting ethane or propane models are always the same. When we proceed to add another tetrahedron to propane, how- ever, 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 the model will represent normal butane, and in the latter isobutane; and so with the other homologues. We may also describe this progression from one hydro- carbon to the next higher as being due to the replace- ment of the H atoms of the former by the group CHg, 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 hydrocarbons 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 corre- sponding derivative of any other member of the series wiU differ from it by just as many CH2 groups as did the original hydrocarbons differ from one another. In inorganic chemistry the halogen compounds, the oxides, and the hydroxides are among the most im- portant compounds of an element, and the same applies to the hydrocarbons: each has halogen derivatives, oxides (ethers), and hydroxides (alcohols). Beyond these, however, the analogy breaks down, for whereas an inorganic hydroxide is an ultimate product and cannot be fiu-ther oxidized, an organic hydroxide (or 86 ORGANIC CHEMISTRY. alcohol) can be oxidized so as to yield various substances according to the extent of the oxidation and the nature of the alcohol started with. We may, therefore, clas- sify 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 tetrachlor methane. In connection with the monohalogen substitution products it should be pointed out that they may be considered as de- rived 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 alkyl, and the specific names for the alkyls are methyl (CH3-), ethyl (C2H5-), propyl (C3H7-), and so on. An alkyl is, therefore, analogous with a monovalent element or with NH4-. Halogen atoms may likewise displace one or more of the H atoms of the alkyl radicle when this latter is already in combination with some other substituting group. Thus, chloral is trichloraldehyde, CCI3CHO, aldehyde being CH3CHO. Oxides (or ethers). Since oxygen combines with two atoms of a monovalent element, as in sodium oxide, Na20, the lowest alkyl oxide wUl have the formula PRELIMINARY SURVEY. 87 QTT^^O. To this group belong the ethers, common ether being c'h!^^- Hydroxides (or alcohols). When one of the H atoms of methane is replaced by hydroxyl, OH, methyl alcohol H H " is formed. Thus H — C — H becomes H — C — OH, and I I H H it does not matter which of the H atoms is thus replaced, the resulting compound being always the same. The same is true for ethane and its alcohol, ethyl alcohol, CHs— CH2OH. 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. 84); we may add the OH group to a C atom of propane which is in combination with three hydrogen atoms or to one in union with two such, and the result- ing product, as we have seen, will exhibit different prop- erties. Consequently we have two forms of propyl alcohol. Of these the OH group in the one is attached at the end of the chain, CH3 — CH2 — CH2OH; in the other it is attached in the middle of the chain, OH I The former is called a primary CH3 — CH — CH3 . alcohol, the latter a secondary alcohol. In the case of butane, we may have the hydroxyl radicle at the end of the chain, CH3— CHg— CH2— CH2OH (primary butyl alcohol) ; or attached to a C atom in the 88 ORGANIC CHEMISTRY. centre of the chain with one other H atom attached to it, CH3 — CH2 — CH<^pTT (secondary butyl alcohol); or — a third possibility — the hydroxyl radicle may be attached to a C atom which is not directly combined CH3 with any other H atom, thus CH3 — C — OH (tertiary I CH3 butyl alcohol). There are, therefore, three varieties of these alcohols: 1. Primary, containing the group ■ — CH2OH 2. Secondary, " " " — CHOH— I 3. Tertiary, " " " — C— OH I . . The essential chemical difference between these is that when oxidized they yield different products. These we shall consider immediately. In all these alcohols only one hydroxyl radicle is present : they are analogous with hydroxides of mono- valent elements such as sodium (thus NaOH is analo- gous with CH3OH). Just as in inorganic chemistry, however, we may have hydroxides with two hydroxyls, Hydrolysis means introducing HiO into the molecule of the substance to be hydrolyzed, resulting in a product quite different from the original substance. 133 134 ORGANIC CHEMISTRY. conform to the general formula, C„H2„02. They are the end products of the oxidation of primary alcohols, of the methyl alcohol series, since they can be obtained by oxidation of aldehydes: H CHO + 0=H COOH. The OH of carboxyl can be proven to be hydroxyl by the reaction with PCI3 (see pp. 112 and 122), thus; 3CH3 -COOH + PCI3 = 3CH3 • COCl + H3PO3. It would be desirable to call this series of acids the formic acid series, since the term fatty is misleading. The boiling-points of these acids increase steadily with increase m the number of carbon atoms. For some unexplained reason a similar statement is not true of the melting-points, but on the contrary the acids having an odd number of carbon atoms have each a lower melting-point than the next acid having one less carbon atom. Formic acid (methanoic acid), H-COOH, is a hquid. (1) It can be made by oxidation of formaldehyde by hydrogen peroxide in alkaline solution (see exp.): H CHO-hH202 + KOH=HCOOK + 2H20. The acid can then be liberated from the potassium formate. FATTY ACrDS AXD ETHEREAL SALTS. 135 (2) Moist CO is absorbed by soda-lime at 190°-220°, forming sodium formate: CO+NaOH = HCOONa ^ (3) Moist CO2 coming in contact with metallic potassium forms potassium formate and potassium bicarbonate : 2K +2CO2 +H2O = HCOOK +KHCO3. (4) Oxalic acid when heated with glycerol (glyc- erine) decomposes to formic acid and carbon dioxide (see exp.). Formic acid occurs in red ants, in stinging nettles, and in the stinging apparatus of bees. It is very irritant, causing blisters when applied to the skin. Formic acid boils at 101°; it solidifies at a low tem- perature and melts at 8.3°. Its specific gravity is 1.2187 at 20*^. It is a strong reducing agent, reducing silver and mercury compounds to the metal (see exp.). The full structural formula, H — C=^0, shows that it I 0— H contains the aldehyde group overlapping the acid group, carbonyl being common to both. It oxidizes to carbon dioxide and water. It is a stronger acid than acetic acid. 'V^'Tien treated with concentrated sul- phuric acid it is decomposed, with evolution of carbon monoxide (see exp.). Experiments. (1) To 0.5 c.c. of commercial for- maline in a beaker add 10 c.c. of 8% NaOH (twice 136 ORGANIC CHEMISTRY. normal solution). Add hydrogen peroxide as long as effervescence continues and let it stand until no odour of formaldehyde remains. Titrate the solution with N y H2SO4 in the following manner: After putting a drop of methyl orange into the solution, run in the acid from a burette gradually, until the mixture remains slightly pink after stirring well. Deduct the number of cubic centimetres of H2SO4 from 20 c.c. (which would be neutralized by 10 c.c. of 8% NaOH); the difference indicates the amount of formic acid which has been produced. This method can be used for quantitative estimation of formaldehyde. (2) Prepare formic acid also as follows : Into a half- litre flask put 50 c.c. of anhydrous glycerol (which has been heated at 170° for an hour); add 50 gm. of crystallized oxalic acid. Suspend a thermometer in the cork, so that its bulb is in the liquid. Heat gradually on a sand bath. Connect with a condenser. Carbon dioxide is evolved and formic acid begins to distil at about 115° (temperature of the liquid). When the temperature reaches 150°, cool the mixture to about 50°, then add 50 gm. of oxalic acid. Heat again up to 150°. If the mixture is overheated acrolein (p. 271) will be produced, which is a very disagreeable gas. Test some of the acid distillate for formic acid as below. If less than 200 c.c. of distillate is obtained, dilute it. In the meantime copper hydroxide has been prepared by treating CUSO4 solution with KOH until slightly alkaline, diluting and filtering. In similar manner, prepare lead hydroxide from lead nitrate solution. Add to half of the formic acid copper hydroxide, warm- FATTY ACIDS AND ETHEREAL SALTS. 137 ing the mixture. When copper hydroxide no longer dissolves, filter and set away for slow evaporation. To the rest of the acid add lead hydroxide and proceed as with the copper formate. C3H5(OH)3+ (C00H)2 =C3H5(0H)20C0H+H20+C02 (Glycerol) (Oxalic acid) (Monoformin or glyceryl monoformate) C3H5(OH)20COH + H20 = HCOOH+C3H5(OH)3. (Formic acid) (Glycerol) (3) Test for formic acid in the distillate as follows: Warm a few c.c. to 50°, add HgO, and shake vigorously. Filter and boil the filtrate one minute; a gray pre- cipitate of mercury develops : HgO + HCOOH = Hg+C02 + H20. (4) Into a test-tube put 3 c.c. of undiluted formic acid; add slowly 6 c.c. of H2SO4. Cork quickly with a cork through which passes a bent deHvery-tube the end of which is to dip into a few cubic centimetres of dilute haemoglobin solution in another test-tube. The hsemo- glqbin is changed to carbon-monoxide-hsemoglobin, which has a cherry-red tint. The haemoglobin solu- tion is made by adding a drop of blood to a little dis- tilled water. Acetic acid, CH3COOH. There are various ways by which ethyl alcohol may be oxidized to yield acetic acid. In the laboratory, the addition of spongy platinum to alcohol contained in an open vessel causes the atmospheric oxygen to attack the alcohol, oxi- 138 ORGANIC CHEMISTRY. dizing it and producmg acetic acid. The spongy platinum itself undergoes no change; it is a catalytic agent, merely transferring the oxygen to the alcohol. Pure alcohol or alcohol diluted with pure water does not spontaneously become converted into acetic acid when exposed to the air, but does so if the dilute alcoholic solution contains nitrogenous matter. This is because of the growth in the latter solution of a microorganism derived from the air {Mycoderma aceti), which, like spongy platinum, transfers atmospheric oxygen to the alcohol. Nitrogenous matter is necessary for the life of this organism. It is in this way that wine becomes converted into vinegar. Mere exposure of wine or cider to air would, however, occupy too much time to produce sufficient vinegar to meet the demands of commerce, and consequently the above process has to be accelerated. This is done by allow- ing the wine to slowly percolate through freely per- forated barrels filled with beech shavings previously sown with the mycoderma by soaking them in strong vinegar. A slight amount of heat is generated during the oxidation; this creates currents of air which enter the barrels through the perforations in their sides, and in this way a sufficiency of oxygen for the process is supplied. Other alcoholic solutions besides wine may be used for the purpose, e.g., cider or beer, and frequently some alcohol obtained by fermenting glu- cose is added to theso. The amount of alcohol in such solutions should not, however, be over ten per cent. The resulting vinegars contain about five per cent of acetic acid, besides various aromatic bodies. To obtain acetic acid in a pure state, fermentation FATTY ACIDS AND ETHEREAL SALTS. 139 of alcoholic liquids is, however, not employed. For this purpose wood is subjected to what is known as destructive distillation. It is heated at low tempera- ture (200°) in an iron retort from which air is excluded, and the vapours condensed. The resulting distillate consists of a mixture of a tarry material and a watery liquid known as pyrohgneous acid. This latter con- tains, besides acetic acid (10%), various other organic substances, particularly acetone (0.5%) and methyl alcohol (1 — 2%); By fractional distillation several of these are separated, the second fraction, which contains most of the acetic acid, being neutralized with quicklime and evaporated; the resulting calcium acetate is then freed of impurities by heating and treated with hydrochloric acid so as to liberate the acetic acid, which is then distilled. This first distillate contains about 36 per cent of acetic acid. To further purify it, this dilute acid is passed through charcoal, and then redistilled over potassium dichromate. The final dis- tillate, however, still contains water. To separate this, the solution is cooled down to a low temperature, when most of the acid solidifies and the water can be drained off. Since pure acetic acid solidifies on cooling, it is often called glacial acetic acid. Acetic acid is a colourless liquid, boiling at 118.1° (corrected) and with a specific gravity of 1.055 at 15°. By dilution with water the specific gravity rises, attain- ing the, maximum when an acid of 80% is obtained (see table in Appendix, p. 408). When glacial acetic acid is cooled it solidifies, the crystals again melting at 16.6°. It has a characteristic odour and, in dilute solution, a pleasant acid taste. 140 ORGANIC CHEMISTRY. Experiments. (1) Into a small fractionating flask put 6 gm. of potassium dichromate and 10 c.c. of concentrated H2SO4; connect with a condenser; then, by means of a dropping funnel suspended by the cork of the flask, add drop by drop 12 c.c. of 20% alcohol. Heat until enough distillate is secured for the following tests. (2) Acetic acid tests, (a) To 5 c.c. of the solution add 1 c.c. of H2SO4 and a few drops of alcohol. Shake, and note the odour of ethyl acetate on warming. (b) Neutralize 5 c.c. with sodium carbonate solu- tion. When neutral add a few drops of ferric chloride solution. The mixture becomes brownish red; on boil- ing a coloured precipitate separates out. Filter; the filtrate is colourless. (3) Cool some glacial acetic acid in a large test-tube by means of ice-water, stirring with a thermometer. Melt the crystals with the heat of the hand, keeping the thermometer in motion, note the temperature at which the acid melts. ■ In all its reactions acetic acid conforms with the structural formula CH3COOH. Since, in our practical exercises, we shall perform nearly all the reactions which have enabled chemists to ascribe this formula to acetic acid, it may be advantageous, when describing these reactions, to indicate how they bear out the structural formula. To illustrate clearly just exactly how a structural formula is arrived at by the chemist let us suppose that we are working with an unknown sub- stance which, by elementary analysis and molecular weight determination (see Chapter III and p. 75), FATTY ACIDS AND ETHEREAL SALTS. 141 we have found to possess the empirical formula C2H4O2. For the sake of clearness of comprehension of the steps of the argument for the structural formula, a tabulated statement will be given before the detailed discussion. (1) C2H3O2 — ^H, proof: monobasic acid. (2) C2H3O — OH, proof: phosphorus chloride reac- tion. (3) CH3 — (OC) — OH, methyl group proven by pro- duction of CH4 from an acetate. (4) CH3— COO— H, proof: the addition of CO2 to CH3Na forming an acetate. (5) Synthetically by the building up of methyl cyanide from CH4, and the hydrolysis of the cyanide to acetic acid. (1) In testing the reaction of this substance we shall have found it acid, and on neutralizing it with monacid bases and evaporating, crystalline salts will be obtained which on analysis will be found to contain one H atom less than the acid itself. These facts indicate that the acid dissociates into a cation of hydrogen, H', and an anion represented by the remainder of the molecule, C2H3O2'. In other words, one of the four H atoms must be represented in the structural formula as dif- ferent from the others: C2H3O2 — ^H. The hydroxides which may be employed to neutralize 142 ORGANIC CHEMISTRY. the acid are conveniently divided into metallic and organic. Metallic salts of acetic acid — the acetates — are very numerous. Sodium and 'potassium acetates (C2H3O2K; C2H302Na) are extensively used for various purposes in the laboratory. Lead acetate, Pb(C2H302)2, on account of its possessing a peculiar sweetish taste, is kno\\n as sugar of lead. It is used in mecJicino as an astringent. "When it is mixed with lead oxide the r H o In the presence of carbonic acid, basic lead acetate forms densely opalescent solutions on account of the insoluble lead carbonate which is formed. In boiled distilled water the solutions are nearly clear. The lead acetates are valuable precipitating reagents and are extensively employed for this purpose in bio-chemistry. Copper acetate is a well-known salt and is used as a reagent. All these acetates are most simply prepared by dissolving the metallic hydroxides in acetic acid. Ethereal Salts of Acetic Acid. In studying alcohol we saw that its hydroxyl group (OH) is replaceable, for example, by halogens (CI, Br, or I), or, as in (he case of ethereal salts, by the organic acid radicle C2H302. Since the ethereal salts are of considerable importance and are numerous, we shall postpone their consideration till later. (2) So far we have seen that one of the H atoms in acetic acid differs considerably from the others. By another set of reactions we can show that this same H atom must be intimately connected with one of the atoms, the resulting group, which we have already FATTY ACIDS AND ETHEREAL SALTS. 143 met with in alcohols, being hydroxyl. This hydroxyl is, as we have seen, replaceable by halogens. Thus, when acetic acid is treated with PCI3, the following reaction ensues : 3C2H3O2H + PCI3 =3C2H30C1 + H3PO3. The hydroxyl group is evidently substituted by CI, just as in the case of water or alcohol: 3HOH + PCI3 =3HC1 + P(0H)3. We must therefore assume that acetic acid can under certain conditions be caused to spht up into C2H3O and OH. The former of these is called the acetyl group, the latter is of course hydoxyl. Acetyl chloride, C2H3OCI, belongs to the class of acid chlorides (or acyl halogenides) and may be pre- pared by the method described in the following exper- iment: Experiment. Put 25 c.c. of glacial acetic acid into a fractionating flask. Suspend a dropping funnel by the cork. Attach the flask to a condenser. As a receiver, fit a filtering flask on to the condenser-tube with a cork (see fig. 21), and attach to the side tube of the filtering flaek a calcium chloride tube. All mois- ture must be carefully excluded in this manner. Add to the acid through the dropping funnel 20 gm. of phosphorus trichloride, the flask being immersed in a bath of ice-water. When cooled, substitute a warm bath at 40°-50°. Keep the temperature at this point until the evolution of HCl ceases (have the apparatus under a hood). Bring (he water of the bath to active boiling and distil the acetyl chloride. 144 ORGANIC CHEMISTRY. Fig. 21. It is a colourless Volatile fluid, boiling at 51°. In the presence of water it readily decomposes, as represented in the following equation: CaHsOiCl+HlOH =C2H300H +HC1. The atmospheric moisture is sufficient to cause this reaction, so that when acetyl chloride is exposed to the air it fumes, the fumes being very suffocating and disagreeable. (It should be kept in tightly stoppered bottles.) The H of the hydroxyl group of alcohols reacts similarly with acetyl chloride, thus: C2H3OICI +HiOC2H5 =C2H300C2H5 +HC1, (Ethyl acetate) FATTY ACIDS AND ETHEREAL SALTS. 145 the ethereal salt of acetic acid with the radicle of the alcohol used being formed. On this account acetyl chloride is an invaluable reagent for the detection of alcoholic hydroxyl; if we find that a substance when treated with acetyl chloride forms an ethereal acetate we may conclude that the substance contains hydroxyl other than the hydroxyl of carboxyl. Experiment. To 3 c.c. of absolute alcohol add 3 c.c. of acetyl chloride. HCl is evolved. Note the odour of ethyl acetate. The above experiments, therefore, justify our writing the formula C2H3O — OH. Further corroboration of this is found in the fact that two molecules of acetic acid can be made to unite together with the loss of a mole- cule of water, thus : C2H30G:H p TT n\ C2H3OIOH ^^MsU/ the resulting body being acetic anhydride. For practi- cal purposes acetic anhydride may be prepared by acting on acetyl chloride with anhydrous sodium acetate, thus: + i i =p'2'n>0 +NaCL C2H3O JC] J ^'"'^ It is a fluid giving off a suffocating vapour. Added to water, it sinks to the bottom of the vessel, but gradually becoines reconverted into acetic acid. Its 146 ORGANIC CHEMISTRY. readiness to re-form acetic acid causes it to attaclt the hydroxyl group of alcohols and other hydroxyl com- pounds, one of the acetyl groups becoming thereby attached in place of the OH group, thus: CaHslOH OC^Ial = C2H5OOC2H3 + C2H3OOH. ' ' (Ethyl acetate) (Acetic acid) +^\0C.H3 Like acetyl chloride, it may therefore be employed for ascertaining whether a substance contains hydroxyl not in carboxyl, and if so, how many such groups it contains (see p. 179). (3) There remains for us to find out how the acetyl radicle C2H3O is corn-posed. A clue to this is furnished by the observation that methane, CH4, and a carbonate are obtained by heating anhydrous so(iium acetate with soda-hme (see exp., p. 96) : CaHsOONa+NaOH =Na2C03 + CH4. This must mean that the two carbon atoms are of dif- ferent value and that one of them exists in combination with hydrogen as methyl, CH3. 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: C2H3O • OH +CI2 =C2H2C10 ■ OH +Ha C2H2CIO • OH +CI2 =C2HCl20- OH +HC1, C2HCI2OOH +CI2 =C2Cl30 0H+HCl. FATTY ACIDS AND ETHEREAL SALTS. 147 The resulting substitution products retain the acid properties of acetic acid, such as the power of forming ethereal salts, anhydrides, etc. The chlor-acetic acids are much stronger acids than acetic acid, and the acid power increases with increase in the number of chlorine atoms. (4) If we represent acetic acid as containing a methyl group its formula must be written either CCH3OOH, COCH3OOH, or CH3COOH: which of these is correct? The valence of carbon prevents C of CH3 having more than one linking to the rest of the molecule, also for the other C to satisfy its valence it is necessary that it be linked to both oxygen atoms as well as to C of CH3, therefore, the structure must be CH3COOH. 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 CO2 : CH3Na + C02=CH3COONa. (b) The result of electrolysis of acetic acid. The cation H' is liberated at the cathode; the anion CH3COO' passes to the anode, where it is liberated as CO2 and ethane (the two methyl (CH3) groups from two molecules having united together). (5) By synthesis, as shown by the equations: CH4+Br2=CH3Br+HBr. CH3Br+KCN=CH3CN + KBr. CH3CN+2H20=CH3COOH + NH3 (p. 185). Experiment. Take 2 gm. of acetonitrile (prepared as directed in the experiment under methyl cyanide, see p. 184) and mix with 10 c.c. of 60%- KOH in a 148 ORGANIC CHEMISTRY. t 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. NeutraUze the resulting fluid with HCl and test for acetic acid (see previous experiments): CH3CN +2H2O =CH3 COONHi, CH3 ■ COONH4 +KOH =CH3 • COOK +NH3 +H2O. THE CAUSE OF THE RELATIVE STRENGTHS OF ACIDS {AND BASES). It is important to understand what it is that consti- tutes 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 HCl, H2SO4, 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 effective, the value of this fraction being proportional to the strength of the acid or alkaU. 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. 58), In the case of solutions of strong acids a much greater pro- portion 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 concentration of the hydrogen ions. FATTY ACIDS AND ETHEREAL SALTS. Ii9 (See the table in the appendix, p. 409, for dissocia- tion constants of a number of organic acids.) In the case of bases, e.g., KOH, NH4OH, dissociation in solution into cations of the metal or its equivalent (K,NH4) and into anions of hydroxyl occurs. It is the concentration of the hydroxyl ions (hydroxions) which determines their strength (cf. amines, p. 189). (See the table in the appendix, p. 409, for dissocia- tion constants of certain bases.) In a solution of HCl, for example, there exist: (a) undissociated HCl, (b) cations of H", and (c) anions of CI'; in a solution of acetic acid: (a) undissociated CHs-COOH, (6) cations of H', and (c) anions of CH3COO': but the amount of (a) in the two cases will be very different, there being much less dissociation (i.e., (a) is of greater value) in the case of acetic acid than in the case of hydrochloric acid. In every acid, therefore, there must exist a certain proportion between the undissociated and the dissociated portions. This will, of course, vary at different dilutions, for it will be remembered that dissociation increases with dilution (see p. 61). Since it is known that the electrical con- ductivity of a solution depends on the amount of dis- sociation of the electrolyte dissolved in it, we may obtain a value for this proportion by measurement of electrical conductivity. 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 hydrocar- bon radicle. Thus ethyl acetate has the formula 150 ORGANIC CHEMISTRY. CH3COO -02115, from which it is seen that the two constituent radicles are Hnked together through an oxygen atom as in the ethers (see p. 109). On this 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, C2H5ONO2, and ethyl sulphate, (€2115)2804, are included in this group; but since such as these have been considered elsewhere we shall study at present only those salts in which both basic and acid por- tions are organic. Inorganic salts are immediately formed when solu- tions of an acid and a base are mixed together, 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- +0H') +(H- +Z') = (B- +Z') +H2O.1 (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 : R0H + (H-+Z')=RZ+H20. (Alcohol) (Acid) (Ester) Not only are inorganic distinguished from ethereal salts in their ease of formation but also in their dissoci- abihty in solution, the former being usually entirely dissociated in solution, the latter not at all so. In I This equation will serve as an example of how ions are represented in a reaction. FATTY ACIDS AND ETHEREAL SALTJ^i. 151 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 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 CH3COO' 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, when- ever a slight excess of water comes to exist in the mix- ture, it decomposes the ester into the acid and alcohol, thus: CH3COOC2H5 + H0H<=^CH3C00H + C2H5OH. Such reversible reactions are often represented in equa- tions by two arrows in place of the sign of equality. The mixture comes to a point of equiUbrium when 0.669 part of a gram molecule of ester is present, pro- vided 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 reverse 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 hydrol- ysis is as pronounced as that of the alcohol and acid to cause esterification. The equilibrium is not really static, the action and the reverse action are going on constantly to an equal degree thus maintaining a balance. 152 ORGANIC CHEMISTRY. 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 alcohol 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 litre of the substances on the one side of the equation 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 acid xC alcohol 79 — : 7; 7 — = constant, C ester xC water ' where represents gram-molecules per litre of the reacting substances. It will be evident that if we increase C acid while C alcohol remains constant, then C ester must increase, which leads us to the conclusion that if enough acid be added all the alcohol will become converted into ester, or, conversely, that if more alcohol be added, the acid remaining constant, the same will be true. For example if one gram-molecule of acetic acid and two gram-molecules of ethyl alcohol interact they come to equilibrium when 82.9% of a gram-molecule of ethyl acetate is formed. FATTY ACIDS AND ETHEREAL SALTS. 15G Temperature does not effect the constant to any marked degree, i.e., does not influence the ultimate amoxmt of ethereal salt produced. On the other hand, it greatly influences the rate of reaction, i.e., the time that it takes for the condition of chemical equihbrium to be 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, i.e., the constant, varies only slightly,^ but the rate is much greater for such acids as acetic than it is for such as benzoic, and for primary than for secondary alcohols. The amount of ester produced can be greatly increased by removing the water formed during the reaction, and in some cases this can be accomplished. By removing the ethereal salt as it is formed (e.g., by distillation or crystaUization) much higher yields can also be obtained (see exp., p. 156). Preparation of Ethereal Salts. The more usual meth- ods for preparing ethereal salts are the following: 1. By heating a mixture of the acid and alcohol with sulphuric acid: ethylsulphuric acid is first formed '■ 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+ethyl alochol 67. Acetic acid+amyl alcohol 68.9, benzoic acid+amyl alcohol 70. 154 ORGANIC CHEMISTRY. and then reacts with the acid, sulphuric acid being re-formed (c/. ether, p. 91), thus: (a) C2H5JOH+ Hi • HSO4 =C2H5 ■ HSO4 +H2O. (6) CzHji ■HS04+HiOOCCH3 = C2H5— OOC.CH3+H2S04. 2. By heating a mixture of the acid and alcohol with hydrochloric acid gas : an aciil chloride is probably first formed, which then reacts with the alcohol: (a) CH3CO|OH + h|Cl=CH3CO-Cl+H20. (b) CH3CO;cr+H|OC2H5 =CH3C00 •C2H5 +HC1. 3. Or the second stage of this reaction (b) 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 maimer the acetyl or benzoyl (see p. 144) derivatives of many substances can be produced, and these, being readily purified, are extensively prepared for purposes of identification. The addition of sodium hydroxide accelerates this reaction in the case of benzoyl compounds (see p. 321). 4. By treating a silver salt of an acid with an alkyl halide (as iodide) : CHsCOOi A^ + J IC2H5 =CH3COOC2H5 +AgI. Properties. Esters in a pure state are stable; in watery solution they slowly decompose into acid and alcohol, the decomposition being greatly accelerated by boiling with water and by the action of acids or FATTY ACIDS AND ETHEREAL SALTS. 155 bases. Hydrolysis i 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 odours, often simulating those of fruits, for instance isoamyl acetate has an odour resembling pears. On this account some of them are used as artificial fruit essences (see p. 161). Ethereal salts include the neutral fats (see p. 176). 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 odours. Ethyl acetate is com- monly called acetic ether. From a bio-chemical standpoint the acceleration which acids induce in the hydrolysis of esters is of interest, partly because a method for the quantitative determination of the acid in gastric juice is based on it, and partly because it typifies catalytic action, which is the means possibly by which ferments produce their actions. Catalysis is defined as consisting in acceleration or retardation of reactions which would take place with- out the catalyzer, but more slowly. Neither the acid molecule nor the ions enter into the chemical reaction. "When a chemical agent enters into the reaction 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 1 Hydrolysis of esters is commonly called saponification (see p. 181). 156 ORGANIC CHEMISTRY. varies greatly with the acid employed. HCl and HNO3 produce about the greatest acceleration, whereas the commonest organic acids have only a feeble influence; thus the accelerating influence of oxalic acid is only 19% and of acetic only 0.4% of that of HCl (see table in appendix, p. 410). Now it has been found that the electrical conductivity 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. 148). By this means, therefore, we have a practical method for gauging the relative strengths of acids (see p. 158). Further, if we add dilute solutions of varying con- centrations of the same mineral acid to methyl acetate it will be found that the rate of saponification is pro- portional to the strength of acid added. It is important to n'ote 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 saponifica- tion of methyl acetate which occurs when a known quantity of acid is added, with the amount occurring in a similar solution of methyl acetate having an un- known quantity of the same acid, an estimate can be made of the amount of acid actually present in the lat- ter. 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. Il2S04. Use a three- hole cork; by one hole suspend a dropping funnel, by FATTY ACIDS AND ETHEREAL SALTS. 157 another connect with a condenser, also insert a ther- mometer so that its bulb is in the hquid. 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 about correspond to the rate of distillation. Wash the distillate in the receiving flask with small portions of saturated sodium carbonate solution until the top layer is no longer acid to htmus. Separate with a separating funnel. Add to the acetic ether a cold solution of 20 gm. 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. Redistil on a water bath, noting the boiling-point (77°). Determine the specific gravity (0.905 at 17°). (2) Determine the rate of saponification of methyl ace- tate as influenced by different strengths of acid (HCl). 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 HCl solution of known strength (say 0.4%); to the other add 20 c.c. of HCl more dilute but of unknown concentration; cork each flask and shake. As quickly as possible titrate 5 c.c. of each mix- ture successively with decinormal NaOH, using phenol- phthalein as an indicator. This gives the acidity of each at the begimiing of the experiment. Cork the flasks tightly with rubber stoppers and keep them in an in- cubator at about 40° for three or four hours, then, after shaking and cooling, take 5 c.c. from each and titrate 158 ORGANIC CHEMISTRY. again. The increase in acid (due to acetic acid liberated by saponification) is found by deducting the initial titra- tion from this second titration. The stronger solution causes the greater amount of saponification. To calculate the exact strength of the unknown acid solution by com- parison with the known we must find out the limit of saponification for the known strength; to do this lea,ve the flask containing this acid in the incubator for forty- eight hours, then titrate again. The titration at the end of this period, less the initial titration, gives an acid value called A; this is the number of cubic centi- metres of decinormal acetic acid that can be liberated by saponification 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 / A \ the constant in the formula C =log l-z — y) for each solution, but call the constant of the known solution C- The observed increase in acid content during the three or four hours' incubation is X. Take a particular experiment. A known solution (0.43435% HCl) gave A =24.9 (c.c). The increase (after four hours) in the known solUton was 12.1 (c.c), therefore A -X =24.9-12.1 =12.8: 24.9\ ^'=l°g (12:8) = -2878 With the unknown solution Z=7 (c.c), A -X =17.9: /24.9\ j^) = .1430. FATTY ACIDS AND ETHEREAL SALTS. 159 Now the per cent of HCl in the unknown /C of unknowm , „„, . = I C of known ) ^P^" ^^^* ^Cl in knownl. Therefore per cent = ('HI?) (0.43435) =0.21544. In this particular case the unknown was of exactly half the strength of the known solution. The rate of saponification bears a definite relation to the number of hydrogen ions present in the solu- tion. Therefore with dilute solutions of easily ioniz- able acids (which are completely dissociated), as most mineral 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. 133) that their presence has practically no effect. In consequence, the method is available for determining the per cent of HCl present in gastric juice or stomach contents. It must not be forgotten, however, that the presence of salts (as in stomach contents) can change the rate of saponification from what it would be if only pure acid were present. OTLER FATTY ACIDS. Propionic acid (propanoic acid), CH3 • CH2 ■ COOH, resembles acetic acid. It can be prepared in similar ways as the latter, namely, by oxidation of propyl alcohol, by hydrolysis of ethyl cyanide, and by the action of CO2 on sodiumethyl. In addition it can be made by reduction of lactic acid, thus : CH3-CHOHCOOH+2HI = CH3-CH2COOH+H20+l2. (Lactic acid) 160 ORGANIC CHEMISTRY. 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 CH3 group or in the CH2 group of propionic acid. It becomes necessary, therefore, to dis- tinguish between these two positions in the molecule. This is done by using Greek letters, a and /?. In order to have a rule which 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 position, the second group is in the /? position, and so on; for example, CHs-CHCl-COOH is a-chlorpropionic acid, CH2CI -0112 -COOH is ^-chlorpropionic acid. Butyric acid (butanoic acid), CH3 -0112 -0112 -COOH, is normal butyric acid. Isobutyric add or methylpropanoic acid has the for- mula pTT^/=CH — COOH. Normal butyric acid is fer- mentation butyric acid, and occurs in Limburger cheese, rancid butter, and sweat. It may be prepared by oxi- dation of butyl alcohol and by hydrolysis of propyl cyanide. Butter contains about six per cent of butyrin, which is the glycerol ester of butyric acid (see p. 174); the acid can therefore be obtained by hydrolysis or saponification of butter (see exp., p. 180). Micro- organisms can cause fermentation of butter, with result- ing hydrolysis of the ester (butyrin) and setting free of butyric acid. Butyric acid is soluble in water and vola- tile. Oleomargarule contains very little butyric or other soluble volatile fatty acids. On this account it FATTY ACIDS AND ETHEREAL SALTS. 161 can readily be identified by making an estimation of the volatile acids in the manner to be described later in an experiment (see p. 180). Butyric acid can also be made from cane sugar as foUows: The sugar solution, acidified with tartaric acid, is inoculated with sour nulk: one variety of micro- organisms in the latter "inverts " the sugar into dextrose and laevulose; another variety ferments these monosac- charides, producing lactic acid; while a third variety con- verts the lactic acid into but3Tic acid: C12H22O11 +H2O =C6Hi206 +C6H12O6, (Cane sugar) (Dextrose) (Laevulose) C6H12O6 =2C3H603, (Lactic acid) 2C3H6O3 =CH3 • CH2 ■ CH2 • COOH +2CO2 +2H2. (Butyric acid) Similar fermentation, with production of lactic and butyric acids, may occur in the stomach when the hydro- chloric acid of the gastric juice is deficient in amount or absent altogether. The gases formed (CO2 and H2) cause the flatulence present in such cases. But)Tic acid has the peculiar disagreeable odour characteristic of rancid butter. The ethereal salt C3H7 ■ COOC2HS, ethyl butyrate, re- sembles pineapple in odour. It is used as a flavouring material in place of pineapple juice. Valeric acid (valerianic acid), CH3 • CH2 • CH2 • CH2 • COOH, is the normal acid. Ordinary valeric acid, however, is isovaleric acid, pTx^CH • CH2 • COOH. It occurs in vale- rian root. 162 ORGANIC CHEMISTRY. Amyl valerate, C4H9-COOC5Hii, 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 CH2 groups are of importance. Caproic acid is CH3(CH2)4COOH. Caprylic acid is CH3(CH2)6C00H. Capric acid is CH3(CH2)8C00H. Lawic acid is CH3(CH2)ioCOOH. MyrisHc acid is CH3(CH2)i2COOH. Palmitic acid is CH3(CH2)i4COOH. Stearic acid is CH3(CH2)i6COOH. Arachidic acid is CH3(CH2)i8COOH. Behenic acid is CH3(CH2)2oCOOH. Most of these occur in fats. The lowest acids are volatile with steam and soluble^ The higher acids are non-volatile and insoluble. The melting-point of pal- mitic 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 administration 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-CHs, 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: CHs • CHOH • CH3 + = CH3 • CO • CH3 + H2O or CH3-C-CH3 A '" \ 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. Furthermore many ketones act as reducing agents toward alkaline silver and copper solutions. Some ketones give the fuchsin 163 164 ORGANIC CHEMISTRY. test (see p. 130), particularly those that have CHa-CO — in the molecule. Many ketones form addition com- pounds with acid sulphites and with hydrocyanic acid (c/. aldehydes). Ketones do not polymerize, but they form condensation products. The reaction of phosphorus pentachloride with ketones is similar to that with aldehydes: CH3CO-CH3 + PCls=CH3-CCl2-CH3+POCl3. No hydrochloric acid is produced and a dichlor deriva- tive is formed, therefore a ketone does not contain hydroxyl. The most important ketone is acetone. Acetone (dimethylketone or propanone), CH3CO CHs, is the simplest ketone. It is produced by the dry distillation of calcium acetate. CH3— ?feo/^^ ^ ^^= ■ ^^ ■ *^^3 +CaC03 Commercially, it is prepared from crude wood alcohol (see p. 139). 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. <^gj =2CH3 -CO -CHa +ZnCl2. It is present in the urine under certain conditions, especially in severe cases of diabetes. It is a useful CHa-CO- CI + Zn CHa -CO- CI „ SECONDARY ALCOHOLS AND KETONES. 1G5 solvent. Acetone is a liquid, boiling at 56.3° (corrected) . Its specific gravity is 0.812 at 0°. Nascent hydrogen converts it into secondary propyl alcohol. It does not oxidize to an acid containing the same number of carbon atoms, but to acetic and formic or carbonic acids. Acetone gives the iodoform test. Experiments. (1) Make iodoform, using acetone instead of alcohol (see p. 107). The reactions involved are of the same nature as in the preparation of iodoform from alcohol, in this case the intermediate compound is triiodoacetone, Clg-CO-CHs. (2) Dissolve 2 c.c. of acetone .in dilute H2SO4; add KIV[n04 solution until a pink colour remains on warming. Filter, make the filtrate strongly acid with 20% H2SO4, and distil. Test the distillate for acetic acid (see p. 140). (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), CH3— C^- CCls.is an addition prod- \CH3 uct 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. Brometone, the corresponding bromine preparation, produced from acetone and bromoform, is analogous 166 ORGANIC CHEMISTRY. to chloretone. As a remedy it is used instead of bro- mides. Sulphonal, another hypnotic, is produced form acetone (see p. 194). Some acids are ketone acids containing both the carbonyl and carboxyl groups. Aceto-acetic acid, CH3 ■ CO • CH2 ■ COOH, typifies these and is of importance, since it may occur in the urine (see p. 202). Tertiary alcohols, when oxidized, decompose into coni- pounds 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 niunber of carbon atoms — ^for example, ceryl alcohol, C26H63OH, cetyl alcohol, CH3(CH2)i4CH20H, and melissic alcohol, CsoHeiOH. In waxes some of the alcohol is not in ester combina- tion, but free. Cetyl palmitate has been found in the fat of an ovarian cyst. Lanolin contains some wax esters (see p. 183). CHAPTER XIV. DIACID ALCOHOLS AND DIBASIC ACIDS. DIACID ALCOHOLS. DiACiD alcohols contain two hydroxy! groups. They are comparable to Ca(0H)2. The simplest diacid alco- hol and the only one of importance is glycol (ethandiol) , CH2OH I . The method of preparation shows that both CH2OH 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, 269). From ethylene bromide glycol can be obtained by the action of silver hydroxide: CHzJBr AglOH CH2OH I + =1 +2AgBr. CHziBrAgjOH CH2OH Glycol is a colourless glycerol-hke liquid, of sweetish taste. It boils at 195° and has a specific gravity of 1.128 at 0°. It forms two classes of ethereal salts, according to 167 168 ORGAXIC CHEMISTRY. whether one or both hydroxyls are replaced. Similarly there are two sodium alcoholates of glycol: CHzONa I , monosodium glycolate.i CH2OH CHaONa , disodium glycolate. SHaONa a; The oxidation products of glycol are numerous because of the presence of two primary alcohol groups. There are two aldehydes: CH2OH I , glycolic aldehyde, and CHO CHO I , glyoxal. CHO CH2OH Oxidation of the first gives rise to glycollic acid, \ ; COOH this will be considered under hydroxy-acids (see p. 196). CHO Oxidation of glyoxal gives | , glyoxylic acid; this is COOH really a dihydroxy-acid, as will be seen later (seep. 203). These two acids are monobasic. Complete oxidation of glycol results in the formation of a dibasic acid, oxalic COOH acid, I COOH ' Distinguish from the glycollates derived from glycoUic acid (p. 197"). DIACID ALCOHOLS AND DIBASIC ACIDS. 169 DIBASIC ACIDS. The simplest is oxalic acid. The next members of the p.TT I , and glutaric acid, CH2<^S nr^r^S■ CH2— COOH \bM2— 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 hydroxy-acid. The acids of the oxalic acid series show the same behaviour as regards melting-points as do the acids of the formic acid series (see p. 134). COOH Oxalic acid, | , 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 is made commercially by heating sawdust with caustic potash and soda. After cooling the oxalate is dissolved out of the mass, precipitated by slaked lime as calcium oxalate, and the separated oxalate is treated with sulphuric acid, setting oxalic acid free. Oxalic acid is one of the strongest of all organic acids, because its solution contains more hydrogen ions than the cor- responding solutions of most other organic acids (see p. 148). 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 170 ORGANIC CHEMISTRY. 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 136). Sulphuric acid decom- poses it to carbon monoxide, carbon dioxide, and water. Potassium permanganate in warm acid solution oxidizes it to carbon dioxide and water: 2KMn04 + 5 (COOH) 2 + 3H2SO4 = IOCO2 + K2SO4 + 2MnS04+8H20. Oxalic acid forms two classes of salts, acid and neu- COOH tral. Acid potassium oxalate, \ , occurs in plants, COOK particularly sorrel. Ammonium, potassium, and sodium oxalates are soluble; all other oxalates of metals are practically insoluble. Calcium oxalate frequently occurs in the urine as a crystalline sediment. Oxalic acid is poisonous and has been used for suicidal purposes. Experiments. (1) Preparation of oxalic acid. Heat 200 c.c. of HNO3 in a large flask to 100°. Set in a fume- closet and add 50 gm. of cane sugar. When the evolu- tion of fumes has ceased, evaporate the acid mixture in an evaporating dish to about one fifth 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 DIACID ALCOHOLS AND DIBASIC ACIDS. 171 evolved gases for CO2 (baryta water, as on p. 3) and CO (hEemoglobin solution, as on p. 137). (4) To 5 c.c. of oxalic acid solution add a few drops of H2SO4, warm, then add potassium permanganate solu- tion — it is decolorized. Malonic acid, CH2<('pqqtt, is of importance mainly in bringing about certain organic syntheses. CH2— COOH Succinic acid, | , is normal succinic acid CH2— COOH and may be produced by hydrolysis of /?-cyanpropionic acid: CH2CN • CH2 ■ COOH +2H2O =CH2— COOH I +NH3. CH2— COOH If caustic potash is used to effect hydrolysis, potassium succinate would be formed. If a-cyanpropionic acid be hydrolyzed isosuccinic acid is formed : CH3-CHCN-COOH+2H20=CH3 +NH3. I /COOH ^^\COOH These two acids give different reactions. Normal succinic acid when heated to 235° yields succinic anhydride and water: COOH • CH2 • CH2 ■ COOH =CH2— COv i >0+H20. CH2— CO/ (Succinic anhydride) 172 ORGANIC CHEMISTRY. Isosuccinic acid, however, when heated above 130°, breaks up into propionic acid and carbon dioxide: CHs • CH<^Q§Qg = CH3 • CH2 ■ COOH +CO2. 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. 316). HOOC(CH2)2CO-0— 0— OC(CH2)2COOH. It is an oxidizing agent, and is said to be antiseptic. CHAPTER XV. TRIACID ALCOHOLS, FATS, AND SOAPS. TRIACID ALCOHOLS. CH2OH Glycerol (glycerine or propanetriol) , CHOH, is the i CH2OH only triacid alcohol of importance. Glycerol occurs in fats in combination with fatty acids and oleic acid, as glycerol esters of these aci.ds. By hydrolyzing (i.e., saponifying) fats, glycerol is set free. This is accom- plished commercially by heating fats (at 170-180°) in a closed boiler or autoclave with water and lime. The lime combines with fatty acids, forming insoluble calcium salts, while the glycerol goes into solution. The calcium remaining in solution is precipitated with sulphuric acid. The dilute glycerol solution is then evaporated imder diminished pressure at as low a temperature as possible until its specific gravity becomes 1.24. The crude glycerol is purified by distillation with superheated steam. C.P. glycerol is prepared by treatment of distilled glycerol with animal charcoal and concentration by vacuum distillation. 173 174 ORGANIC CHEMISTRY Glyceryl butyrate or butyrin yields on saponification glycerol and butyric acid, thus: CH2— OOCC3H7 CH2OH CH — OOC ■C3H7 +3H2O =CHOH +3C3H7 -COOH. I I CH2— OOCC3H7 CH2OH The other fats will be considered more fully presently. Pure glycerol is a colourless, syrupy liquid, having a sweet taste. It boils at 290° and has a specific 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-vapour. 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- CH2CI CH2CI CH2CI I i I hydrin respectively: CHOH, CHOH, CHCl. If tri- I I I CH2OH CH2CI CH2CI chlorhydrin 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, propylene dichloride, trichlorhydrin, and finally glycerol: CH3CH2OH -> CH3COOH -^ CH3COCH3-> (Alcohol) (Acetic acid) (Acetone) ^ CH3 ■ CHOH ■ CH3 -> CH3 ■ CH=CH2 -^ (Isopropyl alcoliol) (Propylene) ^ CH3 • CHCl • CH2CI ^ CH2CI • CHCl • CH2CI -» (Propylene dichloride) (Trichlorhydrin) -^ CH2OH • CHOH • CH2OH. (Glycerol) TRIACID ALCOHOLS, FATS, AND SOAPS. 175 Glycerol forms salts with nitric acid. The trinitrate is nitroglycerine or nitroglycerol. It is made by m'xing glycerol with sulphuric and nitric acids, keeping the CH2— 0— NO2 mixture cold. Its formula is CH — 0— NO2. It ex- CH2— 0— NO2 plodes when suddenly heated or percussed, with the formation of nitrogen, nitric oxide, carbon dioxide, and water. It is a yellow, oily liquid. Dsmamite 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. 262) will absorb nitroglycerin, forming a gelatinous mass. Such explosives as cordite and ballistite are prepared in this way. Gelatin dynamite is prepared from resin, collodion gun-cotton, a httle wood pulp and nitroglycerol. Nitroglycerol is a strong poison, causing violent headache and lowering of blood-pressure. In appro- priate dosage it is extremely useful as a medicine. 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 • - . I On oxidation glycerol yields glyceric acid, CHOH, and CH2OH 176 ORGANIC CHEMISTRY. COOH tartronic acid, CHOH. These are studied with the hy- I COOH droxy-p,cids (see pp. 203 and 205). Glycerophosphoric acid consists of one molecule of orthophosphoric acid combined with glycerol, CH2OH • CHOH • CH2 (H2PO4) . Experiments. (1) Heat 1 c.c. of glycerol with 5 gm. of KHSO4 in an evaporating dish until it turns brown. Note the odour (acrolein) (see p. 271). The fumes will blacken a strip of paper that has been mois- tened 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 add CUSO4 until a copious precipitate of Cu(0H)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. Most fats are mixtures of palmitin (glyceryl tripalmitate), stearin (glyceryl tristearate), and olein (glyceryl trioleate). Olein is a liquid. Butyrin, caproin and caprylin are fluid at ordinary temperature, caprin melts at 31°; these are all present in butter. Palmitin melts at 65°. Stearin has the highest melting-point (about 72°). Mutton-fat contains a large percentage of stearin. TRIACID ALCOHOLS, FATS, AND SOAPS. 177 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. CHa— OOCC15H31 I Palmitin is CH— OOC-CisHgi. CH2— OOC-CisHai CH2— OOC-CitHss Stearin is CH— OOC-CitHss- CH2— OOCC17H35 Mixed esters of glycerol can be obtained; some have CH2— OOCC15H31 been proven to occur naturally. CH — OOC-CirHss CH2— OOCC17H35 is a mixed ester. The following 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 which are volatile and soluble, namely, butyric, capric, capryHc, 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. 178 ORGANIC CHEMISTRY. Cod-liver oil contains glycerides of palmitic, stearic, oleic, myristic, erucic and two other unsaturated acids, also cholesterol. Croton oil contains tiglic, cro tonic, 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 seventy per cent, and contains also esters of palmitic and arachidic acids, and some phytosterol. Fat Values. By determining certain analytical values i and by finding the melting-point and specific 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 value indicates the amount of volatile soluble acid present in the fat. When butter or any other fatty substance is saponified so as to free the fat acid and then distilled as described in the experiment below, the volatile acid in the distillate can be readily estimated by titration. The Reichert- Meissl value is the number of cubic centimetres of decinormal acid contained in the distillate from five grams of fatty substance. (2) The acid value of a fat is found by titration of a solution of the fat in alcohol ether mixture with decinormal KOH, using phenolphthalein as an indicator. ' A very satisfactory book on this subject is Chemical Analysis of Oils, Fats, and Waxes, by /. Lewkowitsch. TBI AC ID ALCOHOLS, FATS, AND SOAPS. 179 This determines the amount of free acid present. The acid value is expressed as milligrams 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 value. 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 HCl to find how much KOH remains unneu- tralized. Then the amount in milligrams of KOH combined with fatty acid as soap for each gram of fat taken is readily calculated; this is the saponification value. (1) The ester or ether value of a fat represents the combined acid, being the saponification value less the acid value. (5) The iodine value estimates the amount of unsat- urated acid (e.g., oleic) present. The iodine forms an addition compoimd with the acid (see p. 268). This value is expressed as the grams of iodine taken up by 100 grams of fat. (6) The acetyl value estimates the hydroxyl content. If. glycerol be treated with acetic anhydride, one mole- cule of acetic acid is produced for each hydroxyl group attached (see p. 146) : CHaiUH OC • CHri =CH3 • COOH +CH2 • OOC • CH3 CHOH+0 CHOH I \ I CH3OH OC-CHa CH2OH fGlyceryl monacetate) 180 ORGANIC CHEMISTRY. The reaction can be pushed until all of the hydroxy! 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 "acety- lated," and by estimating the acetic acid in combina- tion with the alcohol, or acids of the fat, the hydroxyl content can be calculated. Partially hydrolyzed fat esters (e.g., a diglyceride) and hydroxy acids are mainly responsible for this value. Such an acid is ricinoleic acid (p. 272) contained in castor oil, also dihydroxy- stearic acid, CH3(CH2)7(CHOH)2(CH2)7COOH, which is present in butter and in castor oil. Experiments. (1) Compare the specific gravity of filtered butter and oleomargarine by successively 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 value. Into a 300 c.c. flask put 5 gm. of filtered butter, 2 c.c. of 60% KOH solution, and 20 c.c. of glycerol. Heat with a small flame, shaking to prevent excessive foaming. In about 5 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 90 c.c. of hot distilled water and shake until the soap is dissolved. Add 50 c.c. of 5% H2SO4 and some small pieces of pumice.i pistil on, a sand ' To prevent bumping. TBIACID ALCOHOLS, FATS, AND SOAPS. 181 bath. Collect 110 c.c. of distillate in a graduated flask. The distilling should be accomplished in 30 minutes. Filter the distillate; take 100 c.c. of the filtrate with a pipette and transfer it to a beaker. Add a little phenolphthalein solution and titrate with decinormal KOH until shghtly pink. Multiply the number of cubic centimeters of alkali by 1.1; this gives the Reichert-Meissl value. For butter this value should not be less than 24. The experiment may be repeated with oleomargarine. (3) Acid value. 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. When fats are hydrolyzed with the aid of alkali, soap is formed. Hence the origin of the term saponification. In the strict sense, saponification means hydrolysis of an ester, the resulting products being an alcohol and an acid. Many use the word loosely as synonymous with hydrolysis. Soaps are metalhc salts of the acids which occur in fats. Ordinary soaps are mixtures of potassium or sodium palmitate, stearate, and oleate. Potassium soap is soft soap, commonly dispensed as green soap. It is of a yellow colour, but in many countries this colour is changed to green by the addition of indigo. It con- tains the glycerol that is freed by saponification. So- dium soap is hard soap. It is freed of glycerol by " salt- 1S2 ORGANIC CHEMISTRY. ing 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 colour. Calcium, mercury, lead, copper, and many other metals form insoluble soaps. Cheap soaps are made with resin, sodium resinate acting similarly to true soa'p. The cleansing action of soap is due to the presence of free alkah in dilute soap solution. Hydrolytic dissocia- tion of soap can be demonstrated as follows: Add phenolphthalein to a concentrated soap solution, and only a slight red colour appears; now dilute with a large quantity of water, when a decided red colour develops (for effect of dilution on dissociation, see p. 60). Thus the dilute soap solution used for washing contains just the right concentration of alkali to do the work and not enough alkah to be injurious. Dirt is held on the skin or clothing by the aid of fatty material; the alkali partly saponifies and partly emulsifies this, with the result that the " grease " can now be rinsed off. The lather also aids mechanically in removing dirt. Experiments. (1) Melt in an evaporating dish about 10 gm. of lard or tallow, add 100 c.c. of 20% KOH and 50 c.c. of alcohol, 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. Boil until completely saponi- fied, adding water as necessary to maintain constant volume. While hot add an equal vohmie of saturated solution of NaCl. Sodium soap will separate as a top layer and finally solidify. TRIACID ALCOHOLS, FATS, AND SOAPS. 183 (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 solu- tion with calcium chloride solution (calcium soap), with lead acetate (lead soap), copper sulphate, and solutions of other metaUic salts. Lanolin is a fat-like substance prepared by purifying wool grease. It contains about 25 per cent of water and will take up more water until it holds 80 per cent. It is more closely related to waxes than to fats, since its esters yield monacid alcohols, such as ceryl alcohol, by saponification. In addition to esters it contains free acids, free alcohols, cholesterol and isocholesterol. CHAPTER XVI. NITROGEN DERIVATIVES. (ALSO PHOSPHORUS AND SULPHUR COMPOUNDS.) NITROGEN DERIVATIVES. These fall into three classes : (1) cyanogen derivatives, (2) substituted ammonias, and (3) nitro compounds. Cyanogen Derivatives. Organic cyanides can be pre- pared by treatment of alkyl halides with potassium cyanide, as CsHsjCr+KiCN =C2H5CN +KC1, (Ethyl ehioride) (Ethyl cyanide) also by anhydrolysis (removal of water) of an acid amide (see p. 218), thus (see exp.) : CHg ■ CONH2 = CH3 • CN + H2O. (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 phosphorus pentoxide. 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. Collect the distillate in a large clean test-tube. Shake the distillate with half its 184 NITROGEN DERIVATIVES. 185 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. Remove the cyanide carefully with a clean dry pipette. Use the product for synthesis of acetic acid (p. 147). 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. 148): CH3CN+2H20=CH3- COOH + NH3 (i.e., CH3COONH4). HON, 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 dilute solution as a remedy. This reaction also shows that the carbon atom of CN is linked directly to the carbon chain. There are cyan- ides, however, in which it is the nitrogen atom of the CN group that is linked to the carbon chain. These are isocyanides or isonitriles. CH3— N=C is methyl iso- cyanide. 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 amine gives rise to the disagreeable vapour of isocyanide; CHCI3 + R— NH2 =R— NC + 3HC1. 186 ORGANIC CHEMISTRY. When an isocyanide is hydrolyzed, an amide and formic acid are formed : CH3 NC +2H2O =CH3NH2 +HCOOH. Experiment. Isocyanide reaction. Mix together 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 pecuUar disagreeable odour of the isocyanide. As soon as 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 replacing in the cyanic acid molecule. Cyan-acids, such as cyan-acetic acid, CH2CN-C00H, 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 am- monias, N^H, contain the group NH^, called the amido or amino group. Secondary substituted amr monias, N^R, contain the imido group, NH. Tertiary \R substituted ammonias, N^R, have aU the hydrogen of ammonia displaced. "■ NITROGEN DERIVATIVES. 187 These are all called amines. They are prepared by the action of ammonia on alkyl halides: CzHsBr + NHs =C2H5NH2 • HBr, (Ethylamine hydrobromide) C2H5NH2 + CsHsBr = (C2H5) 2NH ■ HBr, (Diethylamine hydrobromide) (C2H5) 2NH + CaHsBr = (C2H5) 3N ■ HBr. (Triethylamiae hydrobromide) The HBr is removed by treating the above compounds 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 NH2 groups, as ethylene diamine, NH2— CH2CH2— NH2. The amines may also be prepared by treating an acid amide with sodium hypobromite (see exp.) : CH3 • CONH2 +Br2 +4NaOH =CH3 ■ NH2 +2NaBr (Acetamide) (Methylamine) +Na2C03 +2H2O. (Br forms hypobromite with NaOH.) Experiment. Treat 12.5 gm. of dry acetamide in a half-htre 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, meanwhile keeping the flask cooled with running water. Run this hypobro- mite mixture by means of a dropping funnel rapidly 188 ORGANIC CHEMISTRY. 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 temperature gets above 75°. Keep at 75° for thirty minutes. Add some powdered pumice and distil on a sand bath. Attach an adapter (see fig. 19, p. 103) to the condenser; dip this slightly below the surface of strong hydrochloric acid in the receiving flask (50 c.c. C.P. HCl+50 c.c. of water). Distil until the distillate, tested by detaching the adapter momenta- rily, 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 decanted alcohol into a dry beaker. Crystals of methylamine hydrochloride separate out by coohng. Filter off the crystals; press between filter-paper; keep part as a specimen. Put the rest into a small test-tube, add strong KOH solution; methylamine is evolved. Note the odour and the reaction of the gas to litmus Test its inflammability by corking the test-tube with a cork fitted with a glass tube which has a finely drawn tip, and applying a flame to this tip. Heat the mixture if necessary to secure free evolution of gas. Nascent hydrogen converts an alkyl cyanide into an amine, CHaCN +4H =CH3 CHaNHz. (Methyl cyanide) (Ethylamine) Many amines, particularly the primary ammonia bases, are decomposed by nitrous acid. This is a reac- tion of considerable importance. An ammonium nitiite NITROGEN DERIVATIVES. 189 derivative is formed first, but this is so unstable that it breaks down, Ubsrating nitrogen : NH2 -CaHs +HNO2 =NH3(C2H5) -NOa, (Ethylamine) (Ethyl ammomum nitrite) NHaCCaHs) -NOa =N2 +H2O +C2H5OH. Many amines result from decomposition of protein material. Amines resemble ammonia in odour, and their vapours 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 (C2H5)4N0H (cf. NH4OH). 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, KOHandNaOH=98 (C2H5)4NOH=79 NH40H=2 Methylamine, dimethylamine, and trimethylamine are gases. They are contained in herring-brine. They are also obtained by destructive distillation of the residue which is left after preparing alcohol from the molasses of beet sugar. HCI is used to hold the amines as salts. This amine distillate is used commercially to produce methyl chloride, because the latter can be 190 ORGANIC CHEMISTRY. obtained from trimethylamine by treatment with hydrochloric acid : (CH3)3N-HC1 + 3HC1 =3CH3C1 + NH4C1. Choline is a substituted ammonium hydroxide, tri- methylhydroxyethyl ammonium hydroxide: (LU3)3N<^Qjj 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, /CH2CO (CH3)3N<' Analogous to choline and betaine are novaine, CPTJ \ m/CH2-CH2-CH2 -011(0 H)2 (CH3)3Ns^Qjj and carnitine, /CH2-CH(0H)-CH2-C0 (CN3)3N<' \o The lecithins are salts of chohne. The principal lecithin, (distearyl lecithin) contains stearic and gly- cerophosphoric acids in combination with choline, having the formula CH2 — OOCisHsS (Stearic acid) CH— OOC18H35 I /OH CH2— O— PO^ — 0-C2H4N(CH3)30H (Glycerol) (Phosphoric acid) (Choline) NITROGEN DERIVATIVES. 191 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 un- saturated acid of the linoleic acid series, C17H30COOH, while the nitrogenous part differs from choline in having one methyl group instead of three. Muscarine is closely related to choline. It has been suggested that it is the aldehyde corresponding to choline considered as an alcohol: rPR ^ m/CH2-CH0(+H20) (.l/tlsjsJN^Qjj It is a basic substance classed as an alkaloid (see p. 382). Muscarine is very posionous and is contained in toad- stools {Agaricus muscarius) and some other plants. Many ptomaines 1 are amine bases. Methylamine, dimethylamine, trimethylamine, ethylamine, diethyl- amine, triethylamine, propylamine, butylamine, amyl- amine, muscarine, and choline occur as ptomaines. ^ 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. 192 ORGANIC CHEMISTRY. Cadaverine and putrescine are diamine ptomaines. They are are highly poisonous. Cadaverine is p„/CH2-CH2NH2 ^"2\cH2-CH2-NH2' Putrescine has the formula, CH2— CH2— NH2 I CH2— CH2— NH2 Neurine, like choline, is a ptomaine containing oxygen, (CH3)3N<(g|=CH^ Urotropine is hexamethylentetramine, (CH2)6N4, and is obtained by the action of ammonia on formaldehyde. The following structural formula has been suggested, /CH2— N =CH2 NfCHa— N=CH2. ^CHa— N=CH2 Piperazine (spermine) is diethylendiamine. '\CH2— CH; Urotropine and piperazine act as solvents for uric acid (in a test-tube at least). 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 (PHa) and arsine (AsHs). Since NITROGEN DERIVATIVES. 193 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, O^As^CHs. \0H Nitro Compounds. — Nitroparafl&ns have N of the nitro group linked directly to C of the chain, e.g., nitroethane, CH3-CH2 — ^N02. The nitro compounds of the benzenes are much more important than are those of the paraffins, and will be considered later. The Nitrites, ethyl nitrite, C2H5— 0— NO, and isoamyl nitrite, CsHu — — 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. 175), but comes on quickly and is very evanescent. 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. H2S64 from a dropping funnel. Amyl nitrite fornls a top layer; decant it off into a separating funnel. Add some water to the mixture in the flask and shake; more amyl nitrite separates out; decant again. Separate the nitrite from the aqueous liquid. Dry with calcium chloride and distil. Note the colour, odour, and the effect of cautious inhalation (flushing of the face and vascular throbbing) . 194 ORGANIC CHEMISTRY. SULPHUR DERIVATIVES. Sulphur may take the place of oxygen in alcohols or ethers, forming sulphur alcohols and ethers, as CHa-SH (c/. CH3OH), CHa-S-CHs (c/. CH3OCH3). Sulphur alcohols are called mercaptans or thioalcohols . The ethers are dialkyl sulphides. ^Vhen they are oxidized, as with nitric acid, sulphonic acids are formed, CH3-SH + 30=CH3-S03H. The sulphonic acid group is SO3H. Sulphonic acids may be looked upon as sulphuric acid in which an hydroxyl group is replaced by an organic group: on /OH q^ /'C2H5 (Sulphuric acid) {Etliylaulphonio acid) A sulphone is obtained if the hydroxyl of the SO3H group be substituted by an organic radicle. The sul- phonic acids are of more importance in the chemistry of aromatic compounds. There are three ahphatic sulphonic derivatives of importance, because they are used as hypnotics. Sulphonal (sulphonmethane), diethylsulphonedi- methylmethane, pxj /C!<('qq^P^tt'^, is made from ace- tone and ethyl mercaptan. It forms colourless crystals, slightly soluble in cokl water, quite soluble in hot water. SULPHUR DERIVATIVES. 195 Trional (sulphonethylmethane) is C2H5\r,yS02C2H5 J2-n.5\p/S02C2Xl5 CHa/^SOaCzHs' Tetronal is C2H5\p/S02C2H5 Ichthyol consists largely of a mixture of the ammonium salts of certain sulphonic acids derived from the tar, which is obtained by distillation of a bituminous shale (found in the Tyrol) that contains the fossil remains of fishes. CHAPTER XVII. MIXED COMPOUNDS. HYDROXY-ACIDS. Under mixed compounds we shall consider hydroxy- acids, amido compounds, and carbohydrates. 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 replaced 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 hypo- thetical carbonic acid, H2CO3. The lowest typical hydroxy-acid is hydroxyacetic /OTT acid, CHs^^pQQTT, or glycollic acid (mentioned pre- viously under glycol) . Glycollic acid (ethanolic acid) may be prepared in many ways, starting either with an alcohol or an acid: (1) By oxidation of glycol or glycol aldehyde (see p. 168). 196 MIXED COMPOUNDS. HYDROXY -ACIDS. 197 (2) By forming the cyanogen derivatives of methyl alcohol, or, what is the same thing, the cyanhydrin of formaldehyde, then hydrolyzing : H.C/^ + HCN=H.CH<(g^, (Cyanhydrin of formaldehyde) CH2ch2=ch2< >ch2+2h20. \coo:h hok \coo/ This has neither alcoholic nor acidic properties. Hydroxypropionic acids are commonly called lactic acids. Just as there are two mpnochlorpropionic acids a and /?, so there is an a-hydroxypropionic acid and a /3-hydroxypropionic acid. The ^ acid, /OH CH2^ CH2— COOH, shows by its reactions that it is related to ethylene (see p. 269). It is therefore called ethylene lactic acid. It is unimportant. Lactic acid proper, a-hydroxypropionic add, /OH CHs-CH^ — COOH, is known in three forms as isomers. As with some of the amyl alcohols (p. 120), these isomers have identical structural formulae. Isomerism of the kind to be de- scribed now is called stereoisomerism.^ To understand ' Stereochemistry {stereos meaning solid) treats of those chem- ical and physical phenomena that are supposed to be caused by the relative positions in space that are occupied by the atoms within the molecule. MIXED COMPOUNDS. HYDROXY-ACIDS. 199 this it is necessary to conceive of the atoms of the mole- cules as being arranged in space, anti not on one plane as in ordinary formulse. The main carbon atom is thought of as being placed in the centre 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 understanding this. To , represent a-lactic acid, write the groups CH3, OH, H, and COOH at the comers of the tetrahedron, thus: OH CH, COOH Try the effect of interchanging these groups in all pos- sible ways. It will be found that two and only two different arrangements are possible. 1 Further, by hold- ing the tetrahedron representing one combination before a mirror, the image in the mirror will be seen to corre- spond exactly to the other possible arrangement. This is true only in the case of compounds which would be represented as having four different groups at the corners. If two of these groups are the same, only one arrangement is possible and stereoisomerism cannot occur. ^ 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. 200 ORGANIC CHEMISTRY. 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.* Dextrolactic acid rotates it to the right, Isevolactic acid rotates it to the left. As represented by models Isevolactic acid is the mirror- image of dextrolactic acid. Ordinary 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 dextrolactic and Isevolactic acid molecules ; such a substance is called racemic.^ 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 different degree of action on the animal organism according to whether it is the d or I isomer that is acting (see nicotine, p. 386, atropine, p. 388, and cocaine, p. 390). 1 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 CeH.\ ^^^^ CsHe. '\Br The pentavalent N atom has been conceived of as at the centre of a pyramid. 2 Racemic substances are not always mixtures ; the mixtures might better be called conglomerates. The racemic, properly speaking, contain the two active molecules in some sort of molecular combination (c/. tartaric acid). MIXED COMPdUNDS. HYDROXY-ACIDS. 201 Dextrolactic acid (d-lactic acid) is also called sarco- lactic 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 Isevorotatory. Laevolactic acid (i-lactic acid) is obtainable by fer- mentation of dextrose by the Micrococcus acidi Icevo- lactici, Racemic lactic acid {d-, Uactic acid) is a s3Tupy liquid 15° having a specific gravity of 1.2485 at -^5-. It is stronger than most organic acids. This is 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 microorganisms: Ci2ll220ii-|-H20 =4C3H603. (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 Iffivo. d, Z-Lactic acid can be shown to contain dextrolactic acid by growing the mould Penicillium glaucum in a solution of d, l- ammonium lactate: the mould destroys the Isevolactic acid. It may be shown to contain laevolactic acid by fractional crystallization of a solution of strychnine lactate, inasmuch as the Isevolactate crystals are formed first. 202 ORGANIC CHEMISTRY. ^Yhen heated to 150° in dry air lactic acid changes to an anhydride called lactid (c/. glycollic acid, p. 198). Hydriodic acid reduces lactic acid to propionic acid (see p. 159). Experiment. In a retort mix 5 c.c. of lactic acid, 10 c.c. of water, and 5 c.c. of concentrated H2SO4. Connect with a condenser. Heat with a smoky flame. Test the distillate for aldehyde (see. p. 129) and for formic acid (see p. 137): CH3CHOHCOOH=CH3-CHO+H-COOH. /?-Hydroxybutyric acid (/?-oxy butyric acid), CH3CH(0H).CH2-C00H, is pathologically of importance, since it may occur in blood or urine, especially in the disease diabetes. It is Isevorotatory, its specific rotation (p. 260) being —24.12°. It will be noticed that the ketone acid acetoacetic acid (/?-ketobutyric acid) corresponds to the above alcohol acids, just as ketones correspond to secondary alcohols (see also p. 166) : CHg-CHOH-CHaCOOH (cf. CHaCHOH-CHs), CHa ■ CO • CH2 ■ COOH (cf. CH3 ■ CO • CHa) . /?-hydroxybutyric acid can be readily oxidized to acetoacetic acid by hydrogen peroxide. /?-Hydro3£yethylsulphonic acid (isethionic acid), CH2(0H)-CH2-S03H, enters into the synthesis of taurin (see p. 217). MIXED COMPOUNDS. HYDROXY-ACIDS. 203 7--Hydroxy-ac-ds are very unstable. They readily oplit off water to form anhydrides called lactones, thus: CHaCOH) •CH2CH2COOH= (r-Hydroxybutyrio acid) CHj • CH2 • CH2 • CO +H2O. I \ (Butyrolactone) The carbon chain is closed by a linking through oxygen. It is not a typical closed chain, however. The presence of hydrogen ions acts catalytically to hasten the forma- tion of the lactone, and it is supposed that the H ions of v-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, CH2OH I CHOH I COOH. Glyoxylic acid, which has been previously mentioned (p. 168), while classed as an aldehydic acid, is really a dihydroxy-acid, because it holds a molecule of water inseparable from it (c/. chloral hydrate): COOH-CX^JJ +HOH =COOH-C^OH ^(J \0H or CH(0H)2C00H. 204 ORGANIC CHEMISTRY. It is a reducing agent like aldehydes (as chloral hydrate). Experiments. (1) To 20 c.c. of a strong solution of oxalic acid add 1 gm. sodium amalgam; when evolution of gas has ceased, filter. The filtrate is a dilute solution of glyoxyhc acid: COOH , „ COOH i + f} = I +H2O. COOH ' ^ CHO (Oxalic acid) (Nascent (Glyoxylic acid) nyurogen) (2) To 5 c.c. of albumin solution (egg-white solution) add 5 c.c. of the glyoxyhc acid solution, then 5 c.c. of concentrated H2SO4; mix and heat gradually; a bluish- violet color is obtained, due to tryptophan contained in the protein molecule. Most proteins give this test. An example of a trihydroxy-acid is cholic or cholalic acid, C2oH3i(CHOH) • (CH20H)2-C00H. The constitu- tion of the C20H31 portion of the formula is unknown. This is important physiologically, being contained, in combination with glycin and with taurin, in bile. Glycocholic acid has the formula: C20H31 (CHOH) (CH2OH) 2 • CO — HN ■ CH2 • COOH. Tatirocholic acid is C20H31 (CHOH) (CH20H)2C0— NH ■ (CH2)2S03H. Glyciironic acid is an aldehydic tetrahydroxy-acid, CHO -(CHOH) 4 -COOH, the arrangement of the second- ary alcohol groups being the same as in dextrose. It is formed by the animal body from dextrose when it MIXED COMPOUNDS. HYDROXY-ACIDS. 205 is needed to combine with abnormal substances, as drugs or indol (when there is an insufficiency of SO4, see p. 375). It is excreted in the urine as paired glycuronates; these are Isevorotatory. By heating with dilute acid, glycuronic acid is set free; this is dextro- rotatory. It is closely related to monosaccharides, differing only in the change of the CH2OH 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. This may cause a mistake in urine examination. It is not fermentable. It gives the pentose reactions (see p. 245). Monohydroxydibasic Acids. COOH I Tartronic acid, CHOH, has been supposed to take COOH part in the physiological synthesis of uric acid, partic- ularly in birds (see p. 234). CH(OH)— COOH Malic acid is hydroxysuccinic acid, | CH2 COOH It is contained in sour fruits, e.g., apples and cherries. Dihydroxydibasic Acids. COOH I /OH Mesoxalic acid, C<' , is the third exception to the I ^OH COOH 206 ORGANIC CHEMISTRY. rule that two hydroxyls cannot be attached to the same carbon atom, chloral hydrate and glyoxylic acid being the other two exceptions. Tartaric acid is dihydroxysuccinic acid, CH(OH)— COOH I CH(OH)— COOH Here there are two asymmetric carbon atoms (see p. 199) in the molecule. This fact causes a species of stereoisomerism which is more difficult to under- stand than that of lactic acid. With the aid of mod- els it can be clearly understood. Arrange pairs of tetrahedra as shown in the diagram. Dextro-tartaric acid. La3vo-tartaric acid. Fig. 22. Meso-tartario acid. It will be noticed in the case of dextro-siad Icevo-tartanc acids that the groups, OH and OH, H and H, are con- nected by straight lines and are on opposite sides of a line connecting the centres of the tetrahedra; they are diagonally opposite, while the COOH groups are vertically opposite one another, both being at an angle MIXED COMPOUNDS. HYDROXY-ACIDS. 207 of the tetrahedron which points forward. As with the models for lactic acid, these models for active tartaric acids cannot be made identical by turning the model about. Place the Isevotartaric 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 Isevo-tartaric acids (cf. racemic lactic acid)i. There is, however, another inactive tartaric acid which cannot be separated 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, for the arrangement of the groups on the top corresponds to that of laevotartaric acid, while the arrangement at the base corresponds to that of dextro tartaric.2 Racemic and mesotartaric acids differ widely in melting-point and solubility. Ordinary tartaric acid is dextrorotatory. It is con- tained in grape-juice as potassium bitartrate or acid tartrate, H00C(CH0H)2C00K. When wine is pro- duced this salt .separates out, because of its relative insolubihty in dilute alcohol. This crude tartar, or argol, is called cream of tartar when purified. 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 being dissolved liberates car- 1 The racemic tartaric acid crystals, however, are represented by the formula 4C4H6O6+2H2O. 2 It will further be noted that an acid of this variety is not possible in the case of lactic acid. 208 ORGANIC CHEMISTRY. bon dioxide from the bicarbonate. Tartaric acid is obtained from potassium bitartrate by precipitation of 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 odour like caramel. It is very soluble. Dextrotartaric acid can be converted into racemic acid by boiling with an excess of strong sodium hydrox- ide solution. The two methods given for separating racemic lactic acid into the active acids 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). -^ a N ~r^/^ X ^ ^— Fig. 23. The crystals are mirror-images of one another. These can be picked out mechanically; one set furnishes dex- trotartaric acid, the other Isevotartaric acid. Rochelle salts is sodium potassium tartrate, CH(OH)— COONa I +4H2O. CH(OH)— COOK MIXED COMPOUNDS. HYDROXY-ACIDS. 209 This has the power of holding Cu(0H)2 in solution, 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. (I) Heat some tartaric acid in a test-tube, stirring it with a thermometer. Note the melting-point. Remove the thermometer and con- tinue heating. The acid turns brown and emits an odour like scorched sugar.i (2) Prepare tartar emetic. Dissolve 5 gm. of potassium acid tartrate in 50 c.c. of water, add 4 gm. Sb203 and boil. Filter and test some of the filtrate for antimony with H2S. Set aside the rest of the filtrate to secure crystals by slow evaporation. (3) After reading over a description of the polariscope^ and its manipulation, determine the rotary power of a strong solution of tartaric acid. ^ Certain other acids act in the same way, particularly citric, malic, tannic, and gallic. 2 A good description can be found in Cohen's Practical Organic Chemistry, also in Practical Physiology by Beddard, Macleod, etc. 210 ORGANIC CHEMISTRY. Monohydroxytribasic Acids. CH2— COOH Citric acid, C(OH) — COOH, is present in currants, CH2— COOH gooseberries, and lemons. It forms large crystals and is quite soluble. Citrates are valuable medicines (diuretics). Agaric or agaricinic acid is used as a remedy. Its formula is Ci9H36(OH)(COOH)3. Other hydroxyacids that are mentioned elsewhere are dihydroxystearic acid (p. 179) and ricinoleic acid (p. 272). CHAPTER XVIII. MIXED COMPOUNDS (Continued). AMIDO ACIDS AND ACID AMIDES; AMIDO ACIDS. Amido or am!no acids are acids containing an NH2 or amido group. Corresponding to monochloracetic acid, CHzCl-COOH, is aminoacetic acid, CHaNHg-COOH. The simplest amino acid is aminoformic acid, NH2-C00H, called carbamic acid. The free acid is unknown. The salts are unstable, showing a decided tendency to become converted into carbonates. Ammo- nium carbamate is of considerable importance in physi- ology, 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 temperature of 135°-140°: NH2 • COONH4 =NH2 • CO • NH2 +H2O. (Ammonium carbamate) (Urea) Experiment. Prepare ammonium carbamate by bubbling dryC02^ and dry NH3 simultaneously into alcohol contained in a cylinder or graduate. Secure the ' CO.j is obtained by putting marble chips into a bottle or generator and adding HCl by a dropping funnel. 211 212 ORGANIC CHEMISTRY. dry NH3 as previously described (see p. 129). Dry the CO2 by bubbling it through H2SO4. When a consider- able quantity of crystals has been produced, stop the process. Filter off the alcohol; press the crystals be- tween filter-paper. To test the carbamate, dissolve some of the crystals in 5 c.c. of distilled water which has been cooled to 0°; immediately add some CaCl2 solution which has been similarly cooled. No reaction is appar- ent because calcium carbamate in solution is stable at very low temperatures. Now warm the solution; the carbamate decomposes and a heavy precipitate of calcium carbonate appears. Leave the rest of the crys- tals exposed to the air several days; a small amount of a white powder (NH4HCO3) is obtained: 2NH3+C02=CO<(qJ| Ethyl carbamate, or urethane, NH2 -00002116, is used as a hypnotic. Amino acids may be obtained by treating a halogen fatty acid with ammonia, thus : HzNiH +CIIH2C • COOH =NH2 • CH2 • COOH +H01. (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 animo-acids that are considered in this chapter AMIDO ACIDS. 213 are of great importance in physiology. They arc very weak acids. In fact they are amphoteric elec- trolytes, their solutions behaving as if they contained both hydrogen and hydroxyl ions. The amino group gives the basic character to the molecule. Proteins and some other organic compounds act in the same manner. /NH2 Glycocoll (glycin) is aminoacetic acid, €£[2^^^ — COOH. It can be produced from glue (or gelatin) by boiling with dilute sulphuric acid or baryta water. It can be pre- pared by allowing an excess of strong ammonium hydroxide to act on monochloracetic acid for 24 hours. In the animal body it combines with benzoic acid to form hippuric acid (see p. 322), and with cholic acid to form one of the bile acids, glycocholic acid. rOOH ^' ^^ called sarcosin. It can be synthesized from monobromacetic acid and methylamine: CHzBr • COOH +2CH3 -NHa =CH2<^^q^^^ + +NH3<(' CH3 Br • It is a product of decomposition of creatin and of caffeine. Alanin, CH3CHNH2COOH, is a-aminopropionic acid. It can be made from a-chlorpropionic acid by treatment with ammonia. It is isomeric with sarcosin. Serin is hydroxyalanin, -CH^OH-CHNHaCOOH. 214 ORGANIC CHEMISTRY. Valin is a-aminoisovaleric acid, S^JJ^^CHCHNHaCOOH. Leucin is a-aminoisobutylacetic acid, or a-amino- isocaproic acid, /NH2 ^JJ^ >CH -CH2^CH -COOH. ^^Z/ (laobutyl ) j (Aminoacetic acid) This may occur in the urine in certain diseases. It is a decomposition product of protein, being an important end product of tryptic digestion. Isoleucin, njj'/CH — C!H<'qqqjj is contained in certain protein.s. Aspartic acid (asparaginic acid) is- aminosuccinic acid, /NH2 CH^ — COOH CH2 COOH It is obtainable from asparagin and from protein. Glutaminic acid (glutamic acid) is a-aminoglutaric acid, /NH2 ^CH^- — COOH CH2\ ^CHs— COOH Gelatin and caseinogen can be split up so as to furnish a considerable proportion of this acid. Phenylalanin and tyrosin are aromatic mono-amino- acids derived from proteins (see p. 353). The amino AMIDO ACIDS. 215 acids considered thus far have the amino group in the oc-position. Lysin is ae-diaminocaproic acid, NH2 • CHa ■ CH2 ■ CH2 ■ CH2 • CH< \COOH It is one of the products of protein when boiled with mineral acid. Ornithin is aiJ-diaminovaleric acid, NH2 • CH2 ■ CH2 • CH2 • CHC03. \NH2 (H2O NH4/ Of course by the action of alkali NH3 is liberated from the (NH4)2C03, while by the action of acid CO2 is liberated. This reaction is the basis of Bunsen's and Folin's methods of quantitative estimation of urea. Sodium hypochlorite and hypobromite decompose urea, liberating nitrogen : C0(NH2)2 + SNaBrO = N2 + 8NaBr-F CO2 + 2H2O. This reaction is made use of in the usual clinical method 226 ORGANIC CHEMISTRY. for urea estiijiation. Nitrous acid also liberates free nitrogen (see p. 189): CO(NH2)2 + 2HN02=2N2 + C02 + 3H20. When heated strongly, urea yields, among other sub- stances, biuret, NH2-C0-NH-C0-NH2, which gives a reddish-violet colour reaction with caustic soda or potash containing a trace of copper sulphate (biuret reaction). This reaction is given by proteins, by oxam- ido, in fact by all substances containing two groups of CO-NHa linked together either directly (as in oxamide) or through a single nitrogen (as in biuret) or carbon atom (as in CH2<^^qJJJ^^Y or through one or more CO-NH / CO-CONHaN groups I as in | \ NH-C0NH2. CH2-NH2 may take the place of one of the CONH2 groups, as in glycinamide (pp. 221 and 241). Urea acts as a weak monacid base toward certain acids, the nitrate and oxalate being particularly char- acteristic salts. In the common method for extraction of urea from urine, it is precipitated from the~ urine (previously concentrated by evaporation) by treat- ment with nitric acid. The urea is liberated from the nitrate by treating the latter with barium carbonate. Experiment. (1) S3mthesize urea as follows: Heat 25 gm. of 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. AMien the frothing ceases pour on to an iron plate. ACID AMIDES. 227 When it is cool powder the mass, separating out the metalhc lead. Digest this crude cyanate for an hour with 100 c.c. of cool water. Filter through a plaited filter into an evaporating dish. Add to the filtrate 25 gm. of ammonium sulphate which has been dissolved in a small quantity of water. Evaporate to dryness on a water bajh, stirring frequently to prevent crusting over. Cool the residue and powder it in a mortar. Transfer it to a small flask, add 100 c.c. of 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 sinlilar manner. Evaporate the alcohol on a water bath to very small bulk. When cool, urea crys- tals 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 colourless concentrated nitric acid. Place a cover-glass over the crystals and examine under a microscope. (6) In a test-tube melt some dry urea, then heat gently for a minute while gas (NH3) 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 colour is obtained. This is called the biuret reaction (see above) : /NH2 NH2 . 0C< + >C0=NH2— CO— NH— CO— NH2 ^|nh^-"""h|nh/ ^^'"-'' +NH3 (Urea) (Urea) If the heating has been continued beyond a certain point an insoluble compound, cyanuric acid, (HCN0)3, is formed; this results from the combination of one 228 ORGANIC CHEMISTRY. molecule of biuret with one of urea, 2NH3 being elim- inated. Veronal is a urea derivative, being diethylmalonylurea or diethylbarbituric acid. CgHsK /CO— NH\ >C< >C0. C2H5/ \C0— NH/ 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 : /NH2 C0< /CH3 \0— CH< Bromural is another hypnotic, derived from urea It is monobrom-iso-valeryl-urea, CH3 ■ CH ■ CHBr . CO— NH • CO • NH2 CHs CHAPTER XIX. MIXED COMPOUNDS (Continued). ACID IMIDES. COM- PLEX AMIDO AND IMIDO COMPOUNDS, INCLUDING POLYPEPTIDES. ACID IMIDES. These contain the group NH; they are illustrated by CH2— COv succinimide, | />NH. They are formed from CH2— CCK acid amides by loss of ammonia, the amide of a dibasic acid being necessary: CHa-CONHa CHg-CO^ I =1 >NH+NH3. CHz-CONH. CHa-CQ/ (Succinamide) (Succinimide) OTHER AMIDO AND IMIDO COMPOUNDS. Guanidin, NH=C<^TyTTT^, may be considered as an imido derivative of urea, and might be called imido- carbamide. It can be synthesized from cyanamide and ammonia : CN.NH2 + NH3 =NH=rC<^5Jg2 (Cyanamide) ^Ou^niZr 229 230 ORGANIC CHEMISTRY. It is more strongly basic than urea, undoubtedly because of the changing of the carbonyl linking of urea for the naturally basic NH group. Methylgicanidin. TTVr p/NH2 ^J-^— ^\NH(CH3)' occurs as a ptomaine (p. 192). Of more importance are the derivatives of guanidin, namely, creatin and creat'.nin. Creatin is methylguanidinacetic acid, /NH2 /CH3 NH=C ^ N^CHa ■ COOH. Creatin can be synthesized from cyanamide and sarcosin : /NH— CH3 /NH2 CN-NH2+CH2^COOH =NH=(/^/CH3 (Cyanamide) (Sarcosin) XCHa COOH Creatin is present in considerable quantity in muscular tissue. It can be obtained from meat extract. Heat- ing with baryta water converts it into urea, sarcosin, and some other substances. Heating with dilute acid changes it to creatinin. As a rule the appearance of creatin in the urine is pathological. It is reported as occurring normally in the urine of children. Creatinin is creatin less a molecule of water; NH CO NH=C< /CH3 1 . ^N^ CH2 This is always present in normal human urine, about 1.5 gm. being excreted in twenty-four hours. The amount excreted when creatinin containing food (flesh) is debarred from the diet seems to be fixed a quantity AMIDO AND IMIDO COMPOUNDS. 231 for each individual, no matter how much the total nitrogen content of the urine may vary. Creatinin crystallizes in monoclinic prisms. It is readily soluble. In alkaline solution it becomes con- verted, at least in part, into creatin. It reduces Feh- ■ ling's and other alkaline copper solutions, but it holds cuprous oxide in solution; on account of these proper- ties it may mislead in testing for sugar if the urine is concentrated. An alkaline bismuth solution, however, is not reduced by creatinin. Creatinin is precipitated by mercuric chloride and by zinc chloride, these reagents entering into chemical union with the creatinin. Uric acid is a derivative of urea. In uric acid two molecules of urea unite together by linking to an inter- mediate carbon chain, each NH2 group losing one hydrogen atom and becoming NH in order to effect the union: ^NH— rC- 0=C C I CJ >(>=0. 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 products of uric acid resulting from oxidation and hydrolysis: NH— CO I I NH— CO I. CO C— NH. I I NHav I 11 >C0+H20+0=C0 CO-l- >C0. NH-C-NH/ i I NH/ NH— CO (Uric acid) [treated with cold HNO3] (Alloxan) (Urea) 23': II. ORGANIC CHEMISTRY. NH— CO NH— CO CO CO +0 I I NH— CO (Alloxan) [treated with warm HNOs] CO +C02 NH— CO NH— CO (ParaVanic acid) NH— CO III. CO +H2O = CO NH— CO (Farabanic acid) [treated with alkali] NH— CO IV. CO +H2O NH2 COOH (Oxaluric acid) [boiled with water] NH2 COOH. (Oxaluric acid) /NH2 COOH C0< + I \nH2 COOH. (Urea) (Oxalic acid) N—C The presence of the pyrimi(iin ring, C C, in uric I I N—C acid is shown by Travhe's synthesis, which is as follows : Cyanacetic acid and urea are treated with POCI3; the latter removes hydroxyl from the acid, and urea takes its place to form cyanacetyl urea : CH2— CN /CN (1) CH2COOH+NH2CONH2=CO (Cyanacetic acid) (Urea) | +H2O. I NH-C-NH2 (Cyanacetyl urea) AMIDO AND IMIDO COMPOUNDS. 233 Treating cyanacetyl urea with alkali causes a shifting within the molecule, resulting in the formation of the pyramidin derivative, HN-C=0 I I (2) 0=C CH2 . HN— C=NH This is treated with. HNO2, giving HN— C=rO i I (3) 0=C C==NOH. I I HN— C=NH By reduction this becomes HN— C=0 0=C C— NH2, HN-C— NH2. which when acted on by CCIOOC2H5 + KOH gives (Ethyl chlorcarbonate HN— C=0 I I (4) 0=C C— NH— COOC2H5, HN— C— NH2 a pyrimidin derivative of urethane. The potassium salt cf this is heated (dry) to 150°, then later to 180°- 23i ORGANIC CHEMISTRY. 190°. Alcohol is split off, leaving uric acid (as potassium urate) : HN— CO (5) 0=C C— NH\ I II >C=0+C2H50H. HN— C— NH/ (Uric acid) 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— (NH2) / I CO C— (HOH) NH^(H) \ . i >co (H)— NH C— (CI3) NH^(H) (Urea) (Trichlorlactamide) (Urea) The groups in parenthesis do not enter into the uric acid molecule, but unite ta form NH4CI, HCl, and H2O. Dial uric acid, COs'-.TrT QQy>CHOH, appears in the case of birds to be an intermediate bocJy in the synthesis of uric acid by the liver. It is formed by the combination of urea with tartronic acid (p. 205). By the addition of another urea molecule to this, uric acid is produced: AMIDO AND IMIDO COMPOUNDS. 235 ,NH— CO Co/ C— (HOH) + NH^(H) \ I >co = ^NH— C(0) NH/(H) (Dialuric acid (Urea) NH— CO = CO C— NH. >C0 +2H2O. NH— C— NH^ (Uric acid) Analogous synthesis in the case of mammals has not been proven. Uric acid has been synthesized by heating together glycocoU and urea. On the other hand, uric acid when heated in a sealed tube with HCl jaelds glycocoU. 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 HO— C C— NH ii4-N>-0H- 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 beheved to exist mainly in the form of monosodium urate in both the blood and the urine. 236 ORGANIC CHEMISTRY. 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 colourless crystalline powder. It is almost insoluble in cold water and alcohol. Uric acid reduces Fehling's solution, but does not reduce an alkaline bismuth solution. Experiment. (1) Add 5 c.c. of 20% HNO3 to a little uric acid in an evaporating-dish; evaporate to dryness on a water bath. Alloxantin is formed. To the residue add baryta water; a blue colour appears. (2) Repeat the above, but instead of using baryta expose the residue to fumes of ammonia. A red colour 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. /NH— CH— NH . Allantoin, CO | /CO, results from \NH— CO- NHg/ careful oxidation of uric acid by potassium permanga- nate. It occurs in the urine of calves, and at times in human and in dogs' urine. Purin bodies. Uric acid and all the purin bodies con- N— C tain the double-ring nucleus C C— N\ . The main I f >c N— C-N^ ring is the pyrimidin ring; the purin nucleus, therefore, is pyrimidin with a urea residue attached as a secondary ring. The relationship of the purin bodies is shown below : AM I DO AND I MI DO COMPOUNDS. 237 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) (2) C C (5)— N(7)s (3) N— C (4)— N(9)' (Purin nucleus) NH— CO CO C— NHs >C(8) NH— C- -N' / €H (Xanthin (2, 6-dioxy purin) NH— CO CH C— NH N II Vh C— N^ (Hypoxanthin) (6-oxypurin) NH— CO CO C— NCCHa) .. >™ (CH3)N C— N (Tneobromine, dimethylxantliin) (3, 7-diniethyl-2, 6-dioxypurin) (CH3)N— CO I I CO C— N< ^(CHg) I II ^CH (CH3)N— C— N^ (Caffeine, theme, trimethylxanthin) (1, 3, 7-trimethyl-2, 6-dioxypurm) NH— CO I I CO C— NHv I II >co NH— C— NH/ (Uric acid) (2, 6, 8-trioxypurin) 238 ORGANIC CHEMISTRY. N=C— NH2 NH— CO 'II II CH C— NH\ H2N— C C— NH^ N- II >H II II ^CH _C_N^^ N C N^ (Adenin) (Guanin) (6-aminopurin) (2-animo-6-oxypurm) 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 nu- clein bodies. Caffeine and theobromine when taken as food are excreted in the urine partly unchanged and partly as monomethyl and dimethyl xanthins. Only 35-40 per cent of caffeine and theobromine appear in the urine as purin 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 which is free of purin bodies the amount of purins excreted daily is a fixed quantity for each individual (cf. creatinin) . Some of the purins, mainly xanthin and hypoxanthin, are found in muscle, and therefore in meat extract. Beef tea or a solution of meat extract contains as its organic constituents chiefly creatin, purin bodies, and sarcolactic acid. Theobromine (dimethylxanthin) is found in chocolate and cocoa. It is called an alkaloid (see p. 382). CaflEeine or theine (trimethylxanthin) is the alkaloidal AMIDO AND IMIDO COMPOUNDS. 239 principle in tea and coffee. Both theobromine and caffeine are used as medicines. Experiment. Try the murexide test (see p. 235) on a little caffeine. Repeat, substituting bromine water for HNO3. Pjrrimidin 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, thymin and cytosin. Uracil is 2, 6 dioxypyramidin, NH— C=0 0=C CH. NH— CH Thymin is 5, methyl 2, 6 dioxypyrimidin, NH— C=0 0=0 C— CH3. I II NH— CH Cytosin is 6 amino 2 oxypyrimidin, N=C— NH2 0=0 OH . I II NH— OH As an illustration of a nucleic acid might be mentioned one which has been obtained from a nucleoprotein of the thymus gland. It is believed to consist of the 240 ORGANIC CHEMISTRY. linking together of four hexose (p. 246) and four meta- phosphoric acid molecules with one molecule each of guanin, adenin, thymin and cytosin. To it has been assigned the formula: C43H57Ni503oP4- Leucomaine is a term applied to basic substances found in Hving animal tissues. The purin bodies and the creatinin group of compounds are the chief leuco- maines. DIPEPTIDES AND POLYPEPTIDES. Because of the fact that the decomposition products of proteins include amino-acids (as alanin, glycocoll, leucin, tjTosin, aspartic acid, etc.) and the hexone bases, it has been proposed to explain the structure of the protein molecule as a chaining together of these amino bodies by means of the removal of OH of a carboxyl group of the one amido body and an H of the amido group of another (c/. formation of acid amides), thus: NH2 • CH2 ■ CO NH ■ CH2 ■ COOH; (Glycylglycin) or a more complicated chain, as : — NH • CH • CO— NH ■ CH • CO— NH • CH ■ CO^NH— I I I I . C4H9 CHs- COOH CaHo-CHg-NHa (Leucin) (Aspartic acid) (Lyain) Of course the above is supposed to be only a part of the formula. DIPEPTJDES AND POLYPEPTIDES. 241 This theory of the constitution of protein molecules gives the best explanation of the universality of the biuret test as applied to proteins (see p. 226), the test being due to the many — ^NH-CH-CONH — groups (cf. glycinamide, p. 221). 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 peptides. If two molecules have united, the compound is a dipeptide; for example, glycylglycin, •NH2 CHa -CO-NH -CHa COOH. Polypeptides are built up from more than two mole- cules; they include tripeptides (as diglycylglycin, NH2 • CH2 • CO— NH • CH2CO — NH • CH2 ■ COOH), tetrapeptides, pentapeptides, hexapeptides, etc. A polypeptide composed of three leucin and fifteen glycocoU molecules has been sjnithesized, the formula being C48H80O19N18 and the molecular weight 1213. Certain polypeptides, identical with those produced synthetically, have been obtained by partial hydrolysis of proteins. The more complex polypeptides show certain resemblances to peptones in their reactions. They taste bitter. They are precipitated 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. 242 ORGANIC CHEMISTRY. E. Fischer, who is doing such brilliant work in this line of synthesis, is inclined to doubt whether this com- paratively simple method of Unking 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. 216) and ammonia. They vary widely in the proportion of the different amino acids and bases, contained in their molecules, e.g., haemoglobin has not less than 20 per cent of leucin, but gelatin only about 2 per cent; on the other hand there is 16.5 per cent of glycocoll in gelatin and none in haemoglobin. The most important classes of proteins are protamines, histones, albumins, globulins, phosphoproteins, sclero- proteins, compound proteins (chromoproteins, gluco- proteins and nucleoproteins), derived proteins (coagu- lated proteins, acid and alkali metaproteins, proteoses and peptones) and certain classes of vegetable proteins called glutehns and prolamines (or gliadins). lodothyrin (thyreoiodin) is a derivative of an iodin containing protein, present in thyroid tissue. Oxyproteic acid, C43H82Ni403iS, is a derivative of protein. It is found in the urine, and may be greatly increased in some pathological conditions. CHAPTER XX. MIXED COMPOUNDS (.Continued). CARBOHYDRATES AND GLUCOSIDES. CARBOHYDRATES. This last class of mixed compounds is of very great importance, since it includes sugars and starches. The name carbo{n)hydrates calls attention to the fact that the number of atoms of hydrogen and oxygen present in the molecule bear the same ratio to one another as in water;! therefore a general formula often given for carbohydrates is C„(H20)„. This, however, is misleading, for there are a number of non-carbohydrate substances that conform to this formula, such as acetic acid, C2H4O2, 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. There are four classes of carbohydrates, namely, monosaccharides, disaccharides, trisaccharides and poly- saccharides.^ Monosaccharides are the simplest car- ' It should be pointed out in this connection that the term hydrate as appUed to alkalies is inaccurate, e.g., NaOH, so- dium hydroxide, not a hydrate. 2 These are also called monoses, bioses, trioses and polyoses. 243 244 OROANIC CHEMISTRY. bohydrates. From the linking together of two mono- saccharide molecules disaccharides result. A trisac- charide contains in its molecule three monosaccharide molecules. Polysaccharides have complex mole- cules that can be resolved into many monosaccharide molecules. MONOSA CCH ABIDES. According to the number of carbon atoms present, monosaccharides are called dioses, trioses, tetroses, pen- toses, hexoses, heptoses, octoses, and nonoses. Aldoses are those containing an aldehyde group, while ketoses are those having a ketone group. CH2OH Glycol aldehyde, | , may be considered a diose. CHO Glycerose can be obtained by mild oxidation of glycerol (or lead glycerate) ; it is a mixture of an alde- hyde and a ketone, and since each contains three carbon atoms, they are trioses : CH2OH CH2OH CH2OH CHOH -^ CHOH + CO CH2OH CHO CH2OH (Glycerol) (Glyceric aldehyde) (Dihydroxyacetone) CH2OH (Glycerose) CHOH Tetrose, | , can be obtained by polymerization CHOH CHO of glycol aldehyde. A ketose tetrose also occurs. CARBOHYDRATES AND GLUCOSIDES. 245 The chief pentoses are c^-arabinose and Z-xylose The following formulae represent their isomeric rela- tion: CH20H CH2OH 1 HO-C H HO— O-H HO— C— H H-C— OH H— C— OH HO— C-H CHO (d-arabinoae) CHO (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 solution and form osazones with phenylhydrazine (the nature of the osazone reaction will be explained presently). Neither is fermented by pure yeast. They give certain, colour reactions which will be illustrated in the experi- ment below. Most of the monosaccharides thus far considered have not been found in natural products. Several methyl derivatives of monosaccharides occur in glucosides, as digitoxose, C6H12O4, a dimethyltetrose, 246 ORGANIC CHEMISTRY. digitalose, C7H14O5, a dimethylpentose, and rhamnosc, C6H12O5, a methyl pentose. Experiment. Pentose test. To 2 c.c. of water in a test-tube add 2 c.c. of HCl and warm. Add phloro- glucin, a little at a time, as long as it dissolves. Now add 1 c.c. of arabinose solution, and heat uhtil a red colour is obtained; examine at once with a small spectro- scope, 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 col- oured and gives the same spectroscopic appearance as above. The hexoses are the sugars of prime importance. The chief ones are dextrose, galactose, and Icevulose; the first two are aldoses, while the last is a ketose: CH2OH CH2OH CH2OH HO— G-H HO— C— H HO— C^H HO— C— H H— C— OH HO— C— H H— C— OH 1 H— C— OH H— C— OH HO— C^H HO C H C=0 CHO CHO CH2OH (Dextrose (d-glucose)) Cd-galactose) (Laovulose (d-fructose)) The aldoses have four asymmetric C atoms, therefore eight main arrangements of the secondary alcohol groups together with their mirror images make sixteen aldose hexoses possible. Twelve of these have been studied. CARBOHYDRATES AND 6LUC0SIDES. 247 d-Mannose differs from d-glucose only in the arrange- ment of the fourth secondary alcohol group. The mirror image aldoses are the Z-hexoses and are IjEVorota- tory. Lsevulose is called d-fructose because the arrange- ment of its secondary alcohol groups is the same as in d-glucose. Six ketose hexoses are known, the only one of im- portance being lsevulose. Two methyl hexoses have been prepared. Condensation of the aldehyde and ketone trioses in glycerose results in the production of a ketose isomeric with lsevulose, thus : CH2OH CH2OH CHOH CHOH CHO + HCHOH = CHOH CO CHOH CH2OH CO (Glyceric aldehyde) (Dihydroxyacetone) I (Glycerose) CH2OH (Ketohexose) Such condensations are commonly called aldol con- densations (see aldol, p. 127). By aldol condensation of six molecules of formaldehyde, formose is obtained, which contains an aldose identical with that obtained from glyceric aldehyde : .R /H /H /H /H H2CO + HCO + HCO + HCO + HCO + HCO = = H2COH • CHOH • CHOH • CHOH • CHOH • CHO. 248 ORGANIC CHEMISTRY. 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- CH2OH I I bitol, (CH0H)4, and can be converted into the latter by CH2OH reduction. Dextrose can be oxidized to the dibasic COOH acid saccharic acid, (CH0H)4. The alcohol duhitol, a COOH stereoisomer of sorbitol, can be oxidized to galactose, and this aldehyde monosaccharide can be oxidized fur- COOH I ther to mucio acid, (CH0H)4. Similarly there are I COOH alcohols and acids corresponding to the other hexoses. Glycuronic acid (p. 204) 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 carbohydrate derivative combined with the protein molecule proper; such are called glucoproteins. This combined sugar has been found in most cases to be an aminohexose, CARBOHYDRATES AND GLUCOSIDES. 249 CH2OH (CH0H)3 generally glucosamine, \ , sometimes galactos- CHNH2 CHO amine. Z-Xylose is found in combination in nucleo- proteins. The sugar group in protein may be detected by certain colour reactions (see exp. below). The question of the possibiUty 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. Attention has been called to the fact that proteins readily spUt up into amino-acids. Reasoning on purely chemical grounds it is possible that amino-acids contain- ing 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: CH2OH CH3 CH, CH2OH CH2OH CH2OH CHNH2 CHNH2 i CHOH I CHOH i CHOH i (CHOH), COOH, serin. COOH, alanin. COOH, lactic acid. COOH, glyceric acid. CHO, glyceric aldehyde. CHO, dextrose-like aldose. The production of dextrose from alanin, glycocoU, aspartic acid and glutaminic acid in the animal body has been exper- imentally demonstrated, lactic acid being noted as an inter- mediate product. 250 ORGANIC CHEMISTRY. Experiment. To 1 c.c. of a strong solution of egg proteid add a drop of saturated solution of a-naphthol in alcohol (acetone-free) ; then with a pipette add 1 c.c. of C.P. H2SO4, so that the acid does not mix, but forms a bottom layer. The greenish colour at the zone of contact is due to the reagents; let the tube stand until a violet ring forms. If the violet colour 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 carbo- hydrate-containing substances. Instead of the alcohohc solution a 10% solution of a-naphthol in chloroform may be used. General Reactions of Monosaccharides. They all reduce alkaline silver, copper, and bismuth solutions, as do other aldehydes and some ketones (see p. 129), All form osazone crystals when treated with phenyl- hydrazine acetate (see exp. below). The reaction occurs in two stages, first the of CO is substituted (as in hydrazones), then secondly the excess of phenylhy- drazine 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 CHoOH is changed to CO in this case. In similar manner rf-mannose gives an osazone which is the same as glucosazone. Methylphenylhydrazine ^ves osazones only with ketoses, and can therefore be used to detect the presence of Isevulose. Glucosazone has the formula CARBOHYDRATES AND GLUCOSfDES. 251 CH2OH I (CH0H)3 C=N-NH-C6H5, I C^N-NHCeHg I H This can be converted by treatment with warm hydro- CH2OH I (CH0H)3 chloric acid into glucosone, | When glucosone CO I CHO is treated with nascent hydrogen (as by using zinc dust), fructose is formed. Thus we can cpnvert an aldose into a ketose. Dextrose and galactose are dexitrorotatory ; Isevulose 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 possible, designated as a and g. This has been investigated 252 ORGANIC CHEMISTRY. in the case of Z-arabinose, d-galactose, lactose and d-glucose. This will be illustrated by d-glucose: CH2OH i HO-C— H C-H CHiiOH HO— C-H 0— H H— C— OH HO— C— H H-C— OH HO 4- -H H— C-OH o-ti-glucoae HO— C-H /3-d-gluoose The a variety, immediately after preparing a solution, has a specific rotation (p. 260) of 110°, the ^ variety 19°, on standing each solution changes and both finally come to a specific rotation of 52.7°; a partly changes to ^ and a partly changes to a, the two come into equilibrium when 40% of the glucose is a and 60% p. Maltose is believed to be made up of two a-d-glucose molecules and isomaltose of two ^-d-glucose molecules. The apparent conversion of the aldehyde group into a secondary alcohol group does not prevent the com- pound giving aldehyde tests. These hexoses are fermented by yeast, giving, as the main products, alcohol and carbon dioxide. Z-Glucose does not ferment, possibly because the optically active enzyme fits only the d-form. In making a test for reducing sugar (dextrose, laevulose, pentose or lactose) in the urine, reduction of Fehling's solution is not sufficient, for the urine may reduce this reagent sUghtly after the administration of turpentine, chloroform, chloral, CARBOHYDRATES AND GLUCOSIDES. 253 phenacetin, saccharin, salicylic acid and balsams, because these bodies are excreted in glycuronic acid combination (see p. 204). While the bismuth test excludes many non-saccharine sub- stances (uric acid and creatinin) that reduce Fehling's solution, it may yet be positive with urine after the administration of antipyrin, salol, turpentine, kairin, senna, rhubarb, benzosol, sulphonal, trional and some other drugs. |The phenylhydrazine test is the most delicate and the most positive. The fermenta- tion test, if positive, is conclusive evidence. 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 boiUng with dilute HCl (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. Pure glucose is crystalline; if crystal- lized from water it contains a molecule of water of crystallization, but if crystalhzed 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. Lsevulose (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 concentration. 254 ORGANIC CHEMISTRY. Experiments. (1) Prepare osazone crystals from dextrose and tevulose as follows: To 100 c.c. of a strong solution of the sugar add 0.25 gm. of phenylhydrazine 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 water acidu- lated with acetic acid, or with cold acetone, press between filter-paper, recrystalHze from a little 80% alcohol, dry the crystals in a desiccator, and later make melting- point determinations.! The osazones of the important sugars have the following melting-points : Dextrose 1 „ „ „ T 1 204°-205° La3vulose J Lactose 200' Maltose 206° (2) Ketose test. To a few cubic centimetres of Isevulose solution add half its volume of HCl. Add a few crystals of resorcin and heat the mixture. A deep- red colour develops, later a brown precipitate which is soluble in alcohol. The alcoholic solution is red. (3) (a) Try the aldehyde tests (see p. 106) with dextrose solution, (b) To some dextrose solution add one fifth its volume of alkaline bismuth reagent (4 gm. Rochelle salts and 2 gm. of bismuth subnitrate dis- ' A quicker and more sati.=factory way of securing osazone crystals is as follows: To 0.5 c.c. phenylhydrazine add 0.5 c.c. glacial acetic acid, after mixing add 10 c.c. of the sugar solu- tion, heat in a boiling water bath; glucosazone crystals appear in 5-10 minutes. For lact- and maltosazone heat 20-30 minutes, hen cool before examining. CARBOHYDRATES AND GLUCOSIDES. 255 solved in 100 c.c. of 10% NaOH), boil five minutes. On cooling a black precipitate separates out. 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 combination of dextrose and Isevulose, lactose of dextrose and galactose, and maltose of two a-d-glucose molecules: C6H12O6 + C6H12O6 =Ci2H220ii + H20. [Jy hydrolysis the constituent monosaccharides are easily obtained : C12H22OH + H2O =C6Hi206 + C6H12O6. Dilute mineral acids and ferments (invertases) bring about this hydrolysis, which is called inversion. Yeast produces an invertase that hydrolyzes maltose quickly and another which hydroly:^es 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. 156) (see appendix, p. 410). Maltose and lactose reduce alkahne copper and bismuth solutions; pure cane sugar does not. After inversion, however, cane sugar reduces these reagents. Therefore FehUng's solution can be used for quantitative 256 ORGANIC CHEMISTRY. estimation of all the sugars treated of in this chapter. 10 c.c. of Fehling's solution is reduced by 0.050 gram dextrose or laevulose. 0.0676 " lactose. 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 to cuprous oxide by disaccharides, but gives reduction with monosaccharides. Maltose and lactose form osazones with phenylhydra- zine, each of these having a characteristic crystalline form and melting-point (see p. 254), while cane sugar forms no such combination provided hydrolysis is guarded against. In order to explain the non-aldehydic action of cane sugar as shown by its behaviour in these two re- actions the following formula has been suggested for it: CH2OH CH2OH -C— H HO— C— H -C— 0^ I HO— C— H — C— H HC— OB H— C— OH ( I HOC— H CH2OH \ \cH Both the aldehyde and ketone groups are tied up by the linking together of their C atoms. CARBOHYDRATES AND GLUCOSIDES. 257 The other disaccharides have the following formulae: Maltose. CH2OH HO— C— H C-H 6 H— C— OH HO— C— H ■ -CH2 HO— C— H — — C— H H— C- -0 HC— OH I HO— C-H (a-d-gluoose Lactose. CH20H HO— C-H H— C H— C— OH HO— C— H H— C= H— C-OH oc-d-glucose) -CH, HO— C-H C-H O (^-galactose -0 + H-C— OH HO— C-H H— C— OH (^-glucose) These disaccharides are all dextrorotatory. Maltose shows the greatest rotary power, lactose the least; maltose and lactose manifest multirotation. Invert- sugar is distinctly Isevorotatory, while the cane sugar from which it is produced is dextrorotatory; this is due to the fact that the laevulose produced (invert- 258 ORGANIC CHEMISTRY. 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 inversion, while that of lactose is increased. Saccharose (cane sugar, beet sugar, sucrose), C12H22O11, 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 vege- tables and plants. The method of commercial preparation of cane sugar is, in brief, as follows: The crushed or chipped material is soaked with water so that the sugar diffuses out; beet chips are first heated to 80-90°, this coagulates the protein of the cell walls and causes rupture of the cells. The sugar extract is treated with lime (removes acids and many impurities), then with carbon dioxide (removes the excess pf lime), and is then evaporated in vacuum pans. On cooling, sugar crystalhzes out. This crude sugar is dissolved, filtered through bone- black (animal charcoal), and recrystallized. The syrup that is left is molasses. Cane sugar as sold is commonly called granulated sugar. Cane sugar forms large crystals when slowly crystal- lized; they are monoclinic prisms. It melts at 160°; at 210°-220° it is converted into caramel with loss of water. It is extremely soluble, 100 gm. of water at 15° dissolves 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 concen- tration; it is lessened by presence of acids, alkalies or salts, but is practically uninfluenced by temperature. CARBOHYDRATES AND GLUCOSIDES. 259 Lactose (milk sugar), Ci2H220ii + H20, is the sugar contained in milk. It occasionally occurs in the urine of pregnant and nursing women. Certain microorgan- isms convert lactose into lactic acid (souring of milk, see p. 201). 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 compoimds with bases. Its specific rotation is not influenced much by concentration or temperature. Maltose, C12H22O11 + H2O, 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 temperature. Isomaltose (gallisin) is distinguished from maltose in that it does not ferment with yeast, and that its osazone has a lower melting-point (150°). ExPBEiMENTS. (1) Produce osazone crystals from lactose and from maltose (see p. 254) . 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. 209). (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 neutralize, and fill up to the mark. Examine this invert-sugar 260 ORGANIC CHEMISTRY. solution (corresponding in concentration to the solu- tion in (a)) with the polariscope. The specific rotation [a]D of the important sugars in 10% solution (at 20°) when sodium light is used are for Dextrose (anhydrous) + 52 . 7° Lffivulose - 93.0° Maltose (anhydrous) + 137 . 04° Lactose (+H2O) + 52. 5° Cane sugar + 66 . 54° Invert sugar - 20 . 2° (—'means rotation to the left.) (3) Test cane sugar before and after inversion (solu- tions of experiment 2, a and b) with Fehling's solution. (4) Try the ketose test (see p. 254) on cane sugar solution. (5) Galactose test. To 10 c.c. of a strong solution of lactose add 3 c.c. of HNO3 and boil for a few minutes. 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, raffinose, consists of d-fructose, d-glucose and (^-galactose linked together as in saccha- rose, none of the CO groups being free. It therefore does not reduce Fehling's solution. Emulsin hydrolyzes it to cane sugar and galactose. Invertase of yeast hydrolyzes it, therefore it ferments. It gives the ketose test. Its specific rotation is -M04°. CARBOHYDRATES AND GLUCOSIDES. 261 POLYSACCHARIDES. These have complex moelcules containing many sugar moelcules linked together. Cellulose, (CeHioOs)^, having a very high molecular weight, is essential to all plants, being the chemical basis of the woody fibre. Cotton-fibre, 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 alkalies and an ammoniacal solu- tion 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. Parchment paper is made in this way. If a solution of cellulose 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 H2SO4, dilute with 200 c.c. of water, and boil for an hour. Neutralize some of this hydrolyzed cellulose solution and test with Feh- ling's solution. (2) Immerse a piece of blotting-paper in 80% H2SO4 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. 1 A substance (probably not a polysaccharide) present along with cellulose in wood. 262 ORGANIC CHEMISTRY. Coat a sheet of cheap white paper with a solution of aniline in HCl; if it turns yellow, lignin is present. 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, pyroxyKn) is trinitro- cellulose. It is explosive. By dissolving guncotton in acetone a gelatinous mass is obtained, then on re- moving the solvent, the guncotton is left in such a physical condition that it burns and explodes more slowly. This substance is used in smokeless powders. The products of the explosion are nitrogen, hydrogen, carbon monoxide and dioxide, and water-vapour. The two lower nitrates are contained in celloidin. Col- lodion is a solution of these nitrates in a mixture of ether and alcohol. Celluloid is made by dissolving them in camphor. 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 NOa groups. Almost pure cellulose, resembling silk, is left. Experiment. Mix 5 c.c. of C.P. HNO3 and 10 c.c. of C.P. H2SO4. When cool immerse some absorbent cot- ton 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 CARBOHYDRATES AND GLUCOSIDES. 263 obtained, and later a glassy skin. Test the inflamma- bility of another piece of the dry cotton, and compare with untreated cotton. Starch (amylum), (C6Hio05)a;, comprises a large part of all vegetable food. It exists in the plant as granules, having different forms and sizes in different plants. Starch grains are supposed to consist of more or less spherical masses of radiating interwoven acicular crystals. When heated with water, the latter is ab- sorbed by the crystals so that the granules swell. Starch and cellulose are probably synthesized by plants from formaldehyde by processes of condensation and polymerization. Ordinary starch is made from com 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 not a true solution, however, but is called a colloidal solution. It is precipitated from solution by low concentration of alcohol, and by saturation with certain salts (as Na2S04 and NaCl). A dilute solution of boiled starch is readily hydrolyzed by ferments (diastase, ptyahn, 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 process further, the end prod- uct being glucose. Heat alone converts starch into dextrin; the crust on bread is mainly dextrin. Starch combines with iodine to form a blue compound; heat drives the iodine out of combination, so that the colour is lost until the mixture becomes cool again. Natural starch contains two different compounds, a soluble 264 ORGANIC CHEMISTRY. substance, amylase (60-80% of the weight of the starch) and an insoluble substance, amybpectin, which gel- atinizes with hot water. Amylopectin gives little color with iodine, amylose gives a deep blue. Both are hydrolyzed by ferments. It may be that there are a large number of closely related amyloses. Dextrin, or more properly dextrins, are less complex bodies than starch. The intermediate substances be- tween starch and maltose, formed during digestion, are, in the order of complexity, amylodextrins, erythro- dextrins, achroodextrins, and maltodextrins. The first give a blue colour with iodine, the second a red or reddish brown (a mixture of erythro- and amylo- dextrins gives a bluish red colour) while the simpler dextrins give no colour 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 ammo- nium sulphate and sodiiun 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)Z) being 192-196° for the higher dextrins. Acid hydrolyzes them to glucose. Diastatic ferments change them to maltose. Glycogen, (CeHioOs)^;, resembles dextrin. It is pres- ent in animal tissues, mainly in the liver. The liver acts as a storehouse for carbohydrates, storing up in the form of glycogen the sugar which comes to it from the digestive organs, and then reconverting the latter CARBOHYDRATES AND GLUCOSIDES. 265 into sugar as needed by the tissues. A. substance has been found in certain vegetables resembling glycogen. Glycogen forms a colloidal solution which is char- acteristically opalescent. With iodine it gives a reddish brown colour. Its (a)Z) is +196.5°. It hydrolyzes to dextrose. Diastatic 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, dextrin, 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 HCl. Gums con%in polysaccharides similar to dextrin. Gum arable (acacia) contains arabin (doHigOg?), which hydrolyzes to arabinose. Oum tragacanth contains bas- sorin. Agar-agar is a pectin-like substance containing at least seven different carbohydrates, including some starch and cellulose. The most important constituent is gelose, (C24H38O19?), 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 medicines. A large number of glucosides have been studied. The sugar derived from them is generally glucose. 266 ORGANIC CHEMISTRY. Phloridzin, C21H24O10, is used to produce exper- imental diabetes in animals. It splits up into glucose and phloretin, C15H14O5 (see also phloroglucin, p. 312). Arbutin, C12H16O7, is a comparatively simple gluco- side, hydrolyzing to dextrose and hydroquinone. Gaultfaerin, CiiHigOs, is a giucoside contained in the wintergreen plant; an accompanying ferment hydrolyzes it to dextrose and methyl salicylate. Salicin, C13H18O7, is used in medicine; it hydrolyzes to dextrose and saligenin (p. 345). Amygdalin, C20H27NO11, is found in bitter almonds, peach-pits, etc. The ferment emulsin, as well as acids, hydrolyze it to glucose, hydrocyanic acid, and benzal- deliyde (see p. 315). Its structural formula is said to be: I 1 CH(CH0H)2CHCH0H-GH2 OCH (CHOH)2CH-CHOH-CH20H. I 1 CeHg— CH— CN Digitalin, C35H56O14, an active principle of digitalis, hydrolyzes to dextrose, digitaligenin, C22H30O3, and digitalose, C7H14O5. Digitoxin, C34H540n, the chief active giucoside of digitaUs, yields by hydrolysis digitoxigenin, C22H32O4, and digitoxose, C6H12O4. Strophanthin, C40H66O19, from strophanthus, hydro- lyzes to strophanthidin, C27H38O7, methyl alcohol, mannose and rhamnose. CARBOHYDRATES AND GLUCOSIDES. 267 Sinigrin, C10H16NS2KO9, the glucoside of black mustard, by the action of a ferment present in the mustard splits up into mustard oil, dextrose and KHSO4. In similar manner sinalbin, C30H42N2S2O15, of white mustard yields dextrose, parahydroxytolyl mustard oil and sinapin bisulphate. Saponins. A large number of glu;!osides are grouped together into this sub-class. They are non-nitrogenous and form a solution which foams on shaking (c/. soaps). Digitonin is a saponin contained in digitalis, C54H92O28 ; it splits up into digitogenin, C30H48O6, and two mole- cules each of glucose and galactose. Artificial glucosides are simpler compounds, for example a methyl glucoside of d-glucose has the CH3 group attached to of the aldehyde group of glucose. Experiments. (1) Try Molisch's test (see p. 250) on a solution of a glucoside. (2) Hydrolyze some glucoside solution by boihng with dilute H2SO4, neutraUze, and examine for sugar with Fehling's solution. CHAPTER XXI. UNSATURATED HYDROCARBONS AND THEIR DERIVATIVES. The most important unsaturated hydrocarbons are the ethylenes and acetylenes. Their unsaturation con- sists in having two or three bonds or Unkings between two or more carbon atoms, thus: C=C, Ci^C, C=C— C=C, C=C=C, etc. 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. 178). Another illustration of the formation of addition compounds is the production of ethylene bromide, C2H4 + Br2=C2H4Br2. Halogen acids (HBr, HI) are added on to these hydrocarbons in similar manner: C2H4+HBr=C2H5Br. The addition compound is, of course, saturated. 268 UNSATURATED HYDROCARBONS. 269 ETHYLENES. Ethylenes or olefins, C„H2„, form an homologous series. Ethylene (ethene, olefiant gas), CH2=CH2, is the only member of importance, and is contained in coal-gas (about 4%). It is colourless and burns with a yeUow flame. Ethylene forms an explosive mixture with oxy- gen. It is obtained by dehydration of alcohol, as by sulphuric acid (see exp. below) : C2H5OH =C2H4 +H2O. ExPEBiMENTS. (1) In a htre flask heat a mixture of 30 c.c. of alcohol and 83 c.c. of C.P. H2SO4 (it is stated that H3PO4 can be used instead of H2SO4, Fig. 24. avoiding the carbonizing) on 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 which is obtained. In- 270 ORGANIC CHEMISTRY. sert a dropping funnel, also a thermometer 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 contains H2SO4, the Woulff bottle (having a safety-tube) contains dilute NaOH solution, each of the last bottles contains 10 c.c. of bromine and 10 c.c. of water, finally a loosely corked flask containing dilute alkali catches any bromine vapour that may pass over. Begin heating the flask, then 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 of tubing. By means of this tube bubble the evolved ethylene through a mixture of solutions of potassium permanganate and sodiima carbonate in a test-tube (Von Baeyer's reagent i) until the pink colour 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 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. 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 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. UNSATURATED HYDROCARBONS. 271 chloride, and cork. After a day or so distil, 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), CH2=CH • CH2OH, is an unsaturated alcohol corresponding to the hydrocarbon propene, CH2=CH-CH3. Its radicle, C3H5, is called allyl. This alcohol can be made from glycerol. Acrolein (acryhc aldehyde), CH2=CH-CH0, is the aldehyde from the above alcohol. It is produced from glycerol (see p. 176) : OH OH H H CH2— CH— CH— =CH2=CH— CHO +2H2O. (Glycerol) (Acrolein) ExPEBiMENT. 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 Schiff's reagent (aldehyde tests). By oxidation it becomes acryUc acid, 0H2=CH • COOH. Crotonic acid, CH3-CH=CH-C00H, and methyl-cro- tonic acid (tiglic acid), CH3-CH=CCH2; cyclopentane, | /CH2, etc. CH2^ CH2-CH2/ They are given the same names as the members of the methane series, with the prefix cyclo. Certain of these cyclic compounds have been found in Caucasian pe- troleum. 275 276 ORGANIC CHEMISTRY. Cycloses. There are a number of hydroxy derivatives of the cychc hydrocarbons; these are cyclic alcohols or cycloses (OH attached to C of the ring). The most important of these is inosite. Inosite, C6H12O6, hexahydroxycyclohexane, has the same empirical formula as the hexoses; it is not a sugar, however. It occurs in animal tissues and in urine, being from this source optically inactive; d and I and dl varieties of inosite are said to occur in plants. BICYCLIC COMPOUNDS. TERPENES AND CAMPHORS. In the volatile oils obtained from coniferous trees (and in various other natural products) are con- tained hydrocarbons having the empirical formula C10H16. These are called terpenes. They decolorize Von Baeyer's reagent (see p. 270), and they combine directly with one or two molecules of HCl. They therefore possess the general properties of unsaturated compounds, but yet they differ from these in many re- spects and may be considered to belong to the class of cyclic compounds since they contain a closed chain of carbon atoms. By mild oxidation many of them can be converted into cymene (paramethylisopropyl benzene) (see p. 297) and by further oxidation into paratoluic acid (see p. 323), both of these substances being aromatic compounds. The terpenes and camphors include many bodies of medical and coromercial value, and of these the following are important: 1. Pinene, CioHie, the principal constituent of oil of turpentine, has the structural formula annexed TERPENES AND CAMPHORS. Ill HoC and exists as stereoisomers. It is dextrorotatory. Its boiling-point is 155°. When combined with hydro- chloric acid it forms pinene hydrochloride, C10II17CI, which, since it resembles camphor,is known as artificial camphor (see exp. below). Artificial camphor can be converted into true camphor. Oil oj turpentine is obtained by incising the bark of fir- trees: the crude oil contains, in addition to turpentine, which is separated by distil- lation, residues constituting rosin. By destructive distillation or by steam distillation of resinous waste wood (pine and fir) are obtained wood turpentine and pine oils. Pinene can be converted by alcohol and nitric acid into terpin hydrate, which is a crystalline substance used in medicine. It is not bicyclic like pinene. Its formula is CH3 C— OH HaC/NcHa H,&\JCB.2 /CH3. CH— C(OH) \c: H, Experiments. (1) Prepare artificial camphor. Into 10 c.c. of freshly distilled turpentine that is free of water (treat with calcium chloride before distilling) 278 ORGANIC CHEMISTRY. contained in a flask kept cool by a freezing-mixture, bubble dry HCl gas until crystals of pinene hydro- chloride appear. Make the HCl by heating in a retort a mixture of dried NaCl and C.P. H2SO4. Collect the crystals on a filter and examine them. (2) Shake some turpentine with Von Baeyer's reagent. Is there evidence of unsaturated linking? 2. Camphor, CioHieO. This is a gum obtained by distilling with steam the finely chopped wood of the camphor tree. Its chemical structure has recently been worked out, and it is now produced by synthetic processes on a commercial scale. Camphor contains a ketone group, so that it CH3 CH2 CH2 -€- -CO may be called a terpene ketone having the formula as shown opposite. In so- lution it is dextrorotatory. Bomeol is a secondary terpene alcohol correspond- ing to camphor, it has CHOH instead of the CO group. Carvacrol (isomeric with thymol) can be obtained CH3 CH3 — C — CH3 CH -CHo CH2 CH2 -COOB CH3— C— CH3 -CH- -COOH {Camphoric acid.) from it by tht loss of two atoms of hydrogen. By warming with phosphorus pentoxide it is converted into cymene. It melts at 17G.4°, and sublimes, the TERPENES AND CAMPHORS. 279 sublimate forming crystals. Hydroxycamphor (oxy- eamphor) has a secondary alcohol group in the place of a CH2 group of camphor. It is one of the newer remedies. Camphor monohromide is.CioHisBrO. Cam- phor can be oxidized to camphoric acid (see formula on page 278). 3. Menthol is a terpene alcohol containing a secondary alcohol group CHOH. Its formula is given below. Like camphor, it contains no unsaturated Hnkings. Menthol is a white crystalHne substance melting at 42°, and is the chief constituent of oil of peppermint. Its solution is Isevorotatory. It is useful as a medicine. It is excreted in combination with glycuronic acid (p. 204). CH3 CH H2C CH2 H2C C\QJJ \/ /t-Ha. CH— CH< ^CH3 Sandalwood oil contains two isomeric unsaturated primary alcohols, one being bicyclic and the other tricyclic. They have the formula, C15H24O. Polyterpenes have two or more terpene rings. 280 ORGANIC CHEMISTRY SUBSTANCES ALLIED TO TERPENES. Caoutchouc or rubber contains a terpene-like sub- stance, CsoHesOio. This is decomposable into 3(CioHi6) + 10H20. Rubber is the hardened milky juice of certain tropical plants. Gutta-percha is similar to rubber. Cholesterol (cholesterin), C27H46O, is an important constituent of bile. It is also present in egg yolk, cod liver oil and lanolin. It belongs to a class of compounds called sterins, which includes also isocholesterol, kopro- sterol, phytosterol and other substances. It has an unsaturated linking and a secondary alcohol group: CH3S yCH • (0112)2 • C17H26 • CH =CH2. CH3/ CHaCHOH-CHa. The portion C17H26 is believed to be related to the polyterpenes. Its crystalhne form is characteristic. It melts at 145-146°. In ether solution it is laevorotatory. Koprosterol, C26H46 ■ CHOH, is a similar compound occurring in the faeces. Phytosterol is of vegetable origin, being most abundant in leguminous seeds and in vegetable oils. It can be detected and distinguished from cholesterol by the fact that its ester with acetic anhydride has a higher melting-point (125°) than the similar ester from choles- terol (114.5"). CHAPTER XXIII. THE AROMATIC HYDROCARBONS. Nearly all of the substances which we have so far studied are represented in their formulae as composed of open chains of carbon atoms. A few of them, such as the anhydrides of hydroxy-acids, lactones, and the purin derivatives, have to be represented as composed of closed chains. It is only in the case of the aromatic bodies and the cyclic compounds, however, that each link in the closed chain is represented by a C atom. In connection with the paraflBn derivatives containing closed clia:ins, moreover, it will be remembered that their closed chain is readily opened, e.g., an anhydride of an acid can easily be converted into the corresponding acid, etc. We come now to a group of organic substances — the largest group, indeed — the members of which are composed of closed chains that cannot readily be opened. In the older chemical nomenclature the bodies belong- ing to this group were called aromatic bodies on account of the presence of an agreeable aroma, and by this name they are still known. They may all be looked upon as derivatives of a substance called benzene, CeHe, just as all the fatty substances may be represented as 281 282 ORGANIC CHEMISTRY derivatives of methane. Many of the derivatives of benzene are indeed quite analogous with those of methane, undergoing similar reactions and possessing much the came properties. Unlike the fatty series, few of them are useful as foods; many of them, how- ever, have very pronounced physiological actions. Commercially they are of very great value. There are four simple reactions in which the two groups^. e., the aromatic and the fatty — give very different results : 1. With concentrated nitric acid the aromatic hydro- carbons readily form nitro compounds, which on reduc- tion with nascent hydrogen yield amino-derivatives. Paraffins are unaffected by HNO3. a. CeHsjH +HOINO2 ^CeHgNOa +H2O. (Benzene) (Nitrobenzene) 6. C6H6N02+6H=C6H5NH2+2H20. (Aniline) 2. With concentrated sulphuric acid they form sul- phonic acids (see p. 193). Paraffins are unaffected by H2SO4. CeHsJH+HOl • SO3H =C6HsS03H +H2O. (Benzene sulphonic acid) 3. Chlor- and brombenzene are very stable and do not readily react with KOH, whereas in the case of methyl chloride, etc., hydroxyl can readily be substituted for the CI (seep. 113). 4. When a benzene substitution product with one or more side chains of carbon atoms is oxidized, the side chain or chains become oxidized in such a way as to form simply carboxyl. THE AROMATIC HYDROCARBONS. 283 BENZENE. At the outset we must study the structure of benzene, since, as has been noted, this is the mother substance of the aromatic bodies. We must furnish evidence that its formula is correctly represented as having a closed chain. Benzene i (benzol), CeHe. When coal is heated in gas retorts, in the preparation of artificial gas, there passes out with the gas a vapour which is condensed in specially arranged condensers. The condensed vapours con- stitute coal-tar. The ammonia and pyridine bases which are also given off from the retorts are dissolved in water. The tar is a mixture of neutral, acid, and a small quantity of basic bodies, and also contains par- ticles of carbon in suspension (hence its blackness) . The tar products are separated, partly by fractional distilla- tion and partly by chemical means. The crude tar is distilled into four fractions, as follows : (1) Light oil (fraction up to 170°). (2) Carbolic oil (170°-230°). (3) Heavy or creosote oil (230°-270°). (4) Anthracene oil (above 270°). The residue contains a large amount of carbon. The light oil is purified by treatment with acid and with alkali and is then distilled. It is in the light oil that most of the benzene and its homologues are contained. The benzene can be further purified by fractional dis- tillation, then by treatment with concentrated H2SO4 to remove thiophene (C4H4S), and finally by freezing it and pouring off the liquid portion. ' Different from benzine (see p. 98). 284 ORGANIC CHEMISTRY. Benzene may also be obtained (1) by distillation of a salt of an aromatic acid with soda-lime, a reduction which, it will be remembered, is analogous with that employed for the preparation of methane: CeHsCOONa +NaOH =Na2C03 +C6H6. (2) By passing acetylene (C2H2) through a red-hot tube. This method illustrates how synthesis of aro- matic out of fatty hydrocarbons can be accom- plished. (3) By heating potassium in a current of CO. A syn- thesis occurs resulting in the formation of C6(0K)6, potassium carbonyl. This is a derivative of benzene and can be converted into benzene by distillation with zinc dust in the presence of water. Benzene is a colourless liquid of aromatic odour, boiling at 80.3° (corrected) (at 80.12° at 757.3 mm.). Its melting-point is 5.4°. Its specific gravity is 0.8736 20° at -rs". Benzene is inflammable and immiscible with 4° water. It is a good solvent for many substances. It can be used for molecular weight determinations (see p. 52). Experiments. (1) Mix thoroughly 25 gm. of benzoic acid and 50 gm. of powdered quicklime, and put into a dry retort (cf. preparation of methane, p. 97). Connect with a condenser and heat gradually. Treat the distillate with dry calcium chloride and redistil from a small fractionating flask (an air-condenser will do). Note the boiling-point. Put the distillate into a dry test- THE AROMATIC HYDROCARBONS. - 285 tube and cool in a freezing-mixture until crystalliza- tion occurs. Remove from the mixture and warm the test-tube with the fingers while stirring the crystals with a thermometer. At what point does the tem- perature remain constant while the crystals are melting? (2) Determine the specific gravity of some pure ben- zene at 15° with the Westphal balance. (3) Shake a few cubic centimeters of benzene with Von Baeyer's reagent. Does it act like an unsaturated compound? Structure of Benzene. From its empirical formula, CeHg, one would expect to find benzene giving reactions like those of acetylene or other unsaturated hydrocar- bons/ that is to say, reactions indicating the existence of double bonds between the carbon atoms. Such, how- ever, is not the case. Benzene does not readily combine / with halogens, i.e., form addition products ; it is not sensi- tive toward oxidizing agents; it does not decolorize a solution of potassium permanganate containing sodium carbonate. Unsaturated compounds readily give all these reactions. It is evident, therefore, that the for- mula for benzene cannot be represented as containing double bonds between the carbon atoms. Further, the formula must represent all the hydrogen atoms as simi- 1 Cf. dipropargyl, CeHe, CH=C— CH2— CHj— C=CH. This has a distinctly greater heat of combustion than benzene, therefore the kind of Unking that we have in benzene must be quite different from that in ordinary unsaturated compounds. 2S6 ORGANIC CHEMISTRY. larly combined with the carbon atoms, for there are no isomers of the monosubstitutwn products of benzene: there is only one monobrombenzene, one monochlorben- zene, etc. This important fact can be shown in a variety of ways. Perhaps the simplest is as follows : If we treat benzene with bromine one of the six hydrogen atoms is re- place 1 by bromine. Numbering the hydrogen atoms 12 3 4 5 6 1 thus: H H H H H H, let us suppose that H is re- placed. Our problem is to see whether the monobromben- zene thus formed is identical with that formed by replace- 2 3 ment of H, H, etc. To do this we must replace another 1 2 3 4 5 6 H in the compound CeBrHHHHH by some group which can then be substituted by Br, the Br originally present being meanwhile replaced by H. This can be accomplished by treating monobrombenzene with nitric acid, the resulting compound having the formula C6H4BrN02. For the sake of argument, let lis sup- 2 pose that H is replaced by the NO2 group, thus: 1 2 3 4 5 6 C6BrN02H: H H H. By the action of, nascent H the NO2 group becomes an amide group, NH2 (see p. 329), and the Br is replaced by H. The formula for our sub- stance is then CgH (NH2) H H H H. (aniline). By treating a salt of aniline (p. 334) with nitrous acid the diazonium salt is formed, which by treatment with hydrobromic acid (see p. 335) yields a monobrombenzene 2 in which the Br atom stands in place of H, and yet this is found to be identical in properties with that mono- 1 brombenzene in which Br was in place of H. By similar reactions the various H atoms may be replaced one by THE AROMATIC HYDROCARBONS. 2S7 one, the resulting monosubstitution product being always the same. This fact makes it evident that we cannot represent the C atoms as linked together in an open chain, for then there would necessarily be two or three varieties : of monosubstitution products, depending upon the particu- lar C atom in the chain to which the substituting group is linked (c/. alcohols, p. 87). On this account Kekul6, who had been a mechanical engineer before he became a chemist, conceived the notion that the C atoms must be represented as forming a ring, and that the formula for benzene must be CH HcV /cH CH or, as it is more usually written, CH HC/XCH HC\/CH CH To satisfy the quadrivalence of the C atom, it is necessary, as shown in the second formula, to assume that certain of these bonds are double. We have, however, seen that 2SS ORGANIC CHEMISTRY. when double bonds between carbon atoms exist, the resulting body is unsaturated. To explain this apparent inconsistency, Kekul6 supposes that in benzene there are really no double bonds in the same sense as they exist in unsaturated hydrocarbons, but that the double bond is dynamic, changing about from place to place, and is really unrepresentable in a formula.^ Collie has made an extremely interesting suggestion as to the spatial relations of the C atoms in benzene. His model represents each C atom as at the centre of a tetrahedron, and neighbouring carbons are attached by bands, while an H atom is attached to each C through the centre of a face not at an angle of the tetrahedron. The rest of the rnodel is mechanical serving for support of the figure (p. 289). Such an arrangement permits rotation of two kinds, (1) the tetrahedra can rotate on their own axes simul- taneously, and (2) the three pairs of tetrahedra can rotate on the axes passing through the centre of the model. This possibility of double rotation conforms very well to the idea that the benzene molecule must be conceived as a system in vibration. By those rotations the model can be made to correspond successively to the following formulae: ' The centric formula fC'>| ' has been proposed to indi- cate pictorially this self-saturation of the carbon atoms of the ring without definite extra linkings. This formula also has the advantage of emphasizing the distinguishing difference of all aromatic from other organic compounds. THE AROMATIC HYDROCARBONS. 289 Fig. 25. 290 ORGANIC CHEMISTRY. The first and last would indicate that there are two sets of H atoms. Possibly this explains why, in the sub- stitution of certain groups for H, there is a tendency to displace alternate H atoms instead of successive ones, for instance nitric acid forms '\ -NOo -NO2 , \ and /\ I J — NO2 O2N —1^ J — NO2 THE AROMATIC HYDROCARBONS. 291 In perfect harmony with this conception of a. ring is the fact that there are three kinds of disubstitution froducts. That three and only three are possible will be evident from the following formulae, where x repre- sents some substituting group : /\ X /\ X /\ /\ /\ \/ \/^ \/^ \/' \/'" \/' X X A (ortho) B (meta) /\ XX \/ ""K/ V/'" C (para) The substituting groups may replace neighbouring hy- drogens, as in the formulae marked A; or be so arranged that a carbon of the ring intervenes, as in B; or vnth two such atoms intervening, as in C. Bodies exhibiting the first arrangement are called ortho, the second meta, and the third para} For certain of the simple disub- stitution products of benzene it has been definitely established which is ortho, which meta, and which para. To ascertain to which of these groups an unknown substance belongs it is necessary to transform it into ' The abbreviations o, m, and p, are used for these terms. 292 ORGANIC CHEMISTRY. one of the known simpler forms, it being considered that the unknown substance contains the same arrangement of its side chains as does the simpler substance which it yields. It remains for us to see, therefore, how it is possible to tell to what class some simple disubstitution product of benzene belongs. This is done by a study of the number of isomeric compounds which can be pro- duced by substituting still another hydrogen atom of the ring by a group different from the other two groups. Suppose y to represent this third substituting group. In an ortho compound we might have y attached next to x, or one carbon atom removed from it, x X X y^ ^x V [ 1 X X /\ X /\. \y y \y y that is to say, there might be two trisubstitution products which on removal of y would yield the same disubstitution product. In a meta compound y might occupy three positions which would be different; thus, between the two x's as in A, or beyond but next to them as in B, or separated from them by carbon atoms of the ring as in C, thus: X X y X THE AROMATIC HYDROCARBONS. 293 That is to say, there are three trisubstitution products which yield the same disubstitution product. In a para compound y could occupy only one position, i.e., next to an x; therefore there is only one trisubstitu- tion product that could be converted into it, thus: y . To take an example: There are six diamine- \/ X /NH2 benzoic acids with the formula C6H3^NH2 . \COOH By removal of the carboxyl group three of these yield diaminobenzenes which are identical in properties (melt- ing-point 63°), and which must therefore be meta; two others yield another variety of diaminobenzene (melting-point 102°) which must be ortho; and the remaining one'yields yet another diaminobenzene (melt- ing-point 140°) and which is para. For convenience of description it is customary to number the carbon atoms in the benzene ring thus: 1 6 2 5 3 When three similar groups (e.g., three hydroxyls) are attached to the benzene ring, only three isomers are possible, symmetrical (positions 1, 3 and 5), unsym- metrical (1, 3, 4) and adjacent (1, 2, 3). Analogous to the alkyl radicles of paraffin hydro- 294 ORGAXIC CHEMISTRY. carbons is the phenyl group, Cetls. This is sometimes designated by the Greek letter 4>- HOMOLOGUES OF BENZENE. The chief homologues of benzene are toluene, CeHs-CHs, the xylenes, C6H4(CH3)2, mesitylene, C6H3(CH3)3, and durene, C6H2(CH3)4. Toluene (toluol), CeHg-CHs, boiling-point 111°, 20° specific gravity 0.8656 at — , can be separated from light oil or can be prepared synthetically by treating a mixture of monobrombenzene and methyl iodide with sodium (c/. synthesis of parafl&ns, p. 95) : CeHsBr +CH3I +2Na =NaI +NaBr +C6H5CH3. This reaction clearly illustrates its structure as methyl benzene. By oxidation the CH3 group becomes car- boxyl, benzoic acid, CeHsCOOH, being therefore formed. Xylenes, C6H4(CH3)2. Being disubstitution products of benzene, there are three of thess. The boiling-point of ortho is 141.9°, meta 139.2°, para 138°; the specific 20° gravity at —5- of ortho is 0.8766, meta 0.8655, para 0.8635. The xylenes can be prepared from light oil. By /CH3 f oxidation they give first toluic acids, C6H4/ i m, N:OOH [ p yCOOH f and then phthalic acids, C6H4^ ] m . The xylol, \coori [ p THE AROMATIC HYDROCARBONS. 295 which is extensively used in histological work and as a fat-solvent, is a mixture of the xylenes.. Isomeric with the xylenes is ethyl benzene, CeHs -02115, which on oxidation yields benzoic acid, CeHgCOOH, instead of toluic or phthalic acid. Mesitylene, C6H3(CH3)3, boiling-point 164.5°, specific 9 8° gravity 0.8694 at ~^j^, is also contained in light oil, and can likewise be obtained by a most interesting and important synthesis, viz., by distilling a mixture of acetone and sulphuric acid (see exp. below). Three acetone molecules no doubt enter into the synthesis, the sulphuric acid removing a molecule of water from each and causing them to condense together into a ring as represented in the following formula. H,C-C Mild oxidation of mesitylene yields mesitylenic acid, /CHa CeHs —CHs , and if this be heated with sOda-hme and \COOH 296 ORGANIC CHEMISTRY. the COOH group be thus removed (see p. 284), meta- xylene is obtained, furnishing corroborative proof that CH3 I metaxylene has the formula J-CH3 Experiment. Preparation of a benzene hydrocarbon (mesitylene) from a fatty compound (acetone). Into a 500 c.c. flask put 100 gm. of clean sand, 50 c.c. of g,cetone, and a cooled mixture of 65 c.c. of C.P. H2SO4 and 30 c.c. of water. Mix thoroughly and allow to stand for at least two days. Filter with the aid of suction, using a hardened filter paper. Distil, using an oil-bath. Shake the distillate with dilute alkali, then with water. Separate the oily layer, dry it with calcium chloride, and distil. Collect the fraction coming over above 150°. Notice the aromatic odour. Test it as fol- lows : Place a few small crystals of anhydrous aluminium chloride in a dry test-tube; heat gradually until a thin coating of sublimate is secured in the upper part of the tube. When cool add a solution of a few drops of the mesitylene in about 2 c.c. of chloroform and cork the tube. Most aromatic hydrocarbons and some of their derivatives give a colour reaction under the conditions of this test, at least on standing. Durene is of on importance. THE AROMATIC HYDROCARBONS. 297 Cymene is paramethylisopropyl benzene, 0 +2C6H40=C6H4< ^ :^(C6H40H)2 + (Phenolphthalein) +H2O. (4) Prepare eosin. Dissolve 2 gm. of fluorescein in 7 c.c. of glacial acetic acid, add to it 0.5 c.c. bromine dissolved in 6 c.c. acetic acid. Mix and warm imtil dissolved. Then add water; red crystals of eosin sep- arate out. To a little of the eosin add NaOH solution, the eosin now dissolves, forming a solution of character- istic red colour. There is a hexabask acid, viz., mellitic, C6(COOH)6, which is found in nature in combination with aluminium as the mineral mellite. CHAPTER XXVII. AROMATIC NITROGEN AND SULPHUR DERIVATIVES. Thehe is very little similarity between the nitrogen 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 im- portance, because they are readily produced and are easily converted into other nitrogenous derivatives. 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.^ The sulphuric acid absorbs the water produced: CeHe + HNOs =C6H5N02 + H20. Its boiling-point is 210°, melting-point 5° and its 20° specific gravity 1.2033 at ^. Experiment. To 80 c.c. H2SO4 in a flask add, while shaking, 70 c.c. of colourless HNO3. Cool thor- 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 1 Mononitrobenzene has the odour of bitter almonds and is known as essence of mirbane. It is poisonous. 327 328 ORGANIC CHEMISTRY. adding the benzene. Attach a vertical air-condenser tube; heat for an hour in a bath kept at 60°, shaldng 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 nitro- benzene becomes the bottom layer). Warm gently with dry calcium chloride in a flask on a water-bath. Distil in a fractionating flask, when the temperature rises above 100° attach an air-condenser, and observe the boiUng-point. Note the odour of the distillate. If, on the other hand, the reaction be allowed to pro- ceed at boiling temperature and with fuming nitric acid the product is dinitrobenzene, a crystaUine substance (needles) melting at 90° (corrected) and boiling at 297°: C6H5NO2 + HNO3 =C6H4^gj + H2O. Three varieties of this are possible (see p. 291). Experiment. Prepare dinitrobenzene {meta). Mix in a beaker 25 c.c. of C.P. H2SO4 and 25 c.c. of fuming HNO3. 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, press between filter-paper, and crystaUize from alcohol. 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 NITROGEN AND SULPHUR DERIVATIVES. 329 nitro groups be introduced into it. The nitro com- pounds are very stable. AMINO COMPOUNDS. The most important reaction of nitro compounds is with nascent hydrogen, whereby they become converted into amino compounds, of which aniline (phenylamine) is the representative : C6H5NO2 +6H =C6H5NH2 +2HaO. (Aniline) Ciommercially, aniline is produced by mixing nitroben- zene with iron fiUngs and hydrochloric acid in an iron cylinder provided with a stirring apparatus, and, when the action is over, adding lime and distilling the anihne. It is a colourless liquid, boihng at 183.7° (corrected); its specific gravity at 16° is 1.024. If not perfectly pure it becomes coloured 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 colour reactions, described in the experiments below. It may be con- sidered as NH3 in which one H is displaced" by CeHs. Like all such bodies (see p. 187), it directly combines with acids to form (anililie) salts, e.g., C6H5NH2-HC1; CfiHgNHa-HNOg; CeHsNHa • H2SO4. The hydrochlo- ride 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. 57). It is, therefore, quite different in this respect from aliphatic amines, which with water form bases, some of which 330 ORGANIC CHEMISTRY. are stronger even than ammonia (c/. p. 189). Phenyl (CeHs) diminishes the basic properties of the amino (NH2) group, whereas fatty residues increase the basic properties of NH2. Whereas nitrous acid decomposes fatty amines with hberation of nitrogen (p. 189), it converts aromatic amines into diazonium compounds (p. 334). Anihne can be liberated from the acid in its salts by distilling with caustic alkah : C6H5NH2 • HCl + KOH =C6H5NH2 + KCl + H2O. It can also be obtained by distilhng 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 5 c.c. each) 100 c.c. of C.P. HCl, 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 temperature, pour into a sep- arating funnel and shake with ether to remove un- changed nitrobenzene. Add 50% NaOH until strongly alkaline; cool the flask if the mixture boils. Distil with steam. "V^Tien the distillate comes clear, stop the process. 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, distil ofif the ether, then distil the aniline, using an air-condenser. MTROGEN AND SULPHUR DERIVATIVES. 331 (2) Tests (a) Dissolve a little KCIO3 in 0.5 c.c. H2SO4; add a few drops of aniline solution — & blue- violet colour appears; dilute with water — the colour changes to red; then add ammonia, and the blue is restored. (6) To a solution of aniline in H2SO4 add a few drops of potassium dichromate solution — a blue colour appears, (c) To some aniline solution (in water) add a filtered solution of bleaching-powder^ — a, purple colour develops. Derivatives of Aniline. The homologues include three toltiidines, C6H4<^-»ttt , of which the ortho and para varieties are important, and six xylidines, CeHsf irrT ^ ^, this large number of isomers being due to differences in the relative positions of the amide and methyl groups. When a mixture of aniline and the toluidines is treated with oxidizing agents a compound known as rosaniline is obtained. This is the mother substance of the anihne dyes. Rosanihne is (NH2C6H4)2C(0H)C6H3/'^g^- Fuchsin is rosaniline hydrochloride. Experiment. Heat together in a test-tube 1 c.c. of aniline, 1 gm. of paratoluidine, and 3 gm. HgCl2 until dark red in colour (15 minutes at 180-200°). Cool partly, extract with alcohol; a deep-red solution is obtained. Filter, evaporate the filtrate. Replacement of one or more of the H atoms of the NH2 group in aniline can be effected in various ways. By reaction with alkyl hahdes secondary and tertiary 332 ORGANIC CHEMISTRY. mixed aromatic fatty amines are obtained. Thus with methyl iodide, methyl aniline and dimethyl aniline are produced : C6H5NH|H + IiCH3=C6HsNHCH3HI and C6H5NHCH3 + ICH3 =C6H5N<(^g3 . jjj Some quaternary base is also formed by the reaction. Dimethyl aniline is commercially the most important of these mixed amines and is prepared by heating aniline hydrochloride with methyl alcohol, methyl chloride being first formed, which then reacts as above. Dimethyl aniline +chIoranil (CiCl^Oz) gives methyl violeti which is a mixture of two salts with the following formulae: /C.H.N(CH3), /C„H,N(CH3). CfC„H,N(CH3), and CeC„H,N(CHa)^ . I \CeH,NCH=HCl \C34N (CH3) ,C1 Methyl violet is also called pyoktanin. Methylene blue (methyl- thionin hydrochloride) has the formula p„ .'N(CHa), ^•^'\N(CH3),C1 In a similar manner replacement with phenyl groups may occur, di- and triphenylamine being produced. Diphenylamine, CeHaNHCeHg, is obtained by heat- ing aniline wilh aniline hydrochloride to 200°: CeHsNHjH + HClNHajCeHs-CeHsNHCeHs+NHiCl. NITROGEN AND SULPHUR DERIVATiyES. 333 Dissolved in concentrated sulphuric acid it is a reagent which detects traces of nitric acid by formation of a deep blue colour. It is changed to tetra-phenylhydra- zine. With acid chlorides, aniline forms anilides, which are analogous with the acid amides (see p. 218) : CHsCOiCl+HiHNCeHs =CH3COHNC6H5 +HC1. (Acetaoilide) One of these, acetanilide (phenylacetamide) , is of very great therapeutic interest on account of its antipjTetic properties. It is the active drug in many proprietary headache medicines (antikamnia, antifebrine, orangine powders, etc.). These remedies are not entirely harm- les'^, since acetmilide acts as a circulatory depressant. Acetanilide is easily prepared by heating aniline with glacial acetic acid (see exp.) : CfiHsNHjH + HOjOCCHa =C6H5 • NH • OCCHo + HgO. (Acetanilide) Experiment. Mix 10 c.c. each of aniUne and glacial acetic acid in a small flask; fit with a long glass tube as a reflux condenser (allows some of the water of reaction to escape, but condenses the acetic acid); boil for four hours. Dilute with 100 c.c. of boiling water and filter at once, using a hot funnel. On cooling, acetanilide crystallizes out. Recrystallize from hot water. Save a sample. Acetanilide is very slightly soluble in cold water and crystallizes from hot water in colourless plates. It 334 ORGANIC CHEMISTRY. melts at 114.2° (corrected). Two other antipyretic drugs are closely related to acetanilide. In one of these, exalgin (methyl acetanilide), the hydrogen atom of the amido group is replaced by methyljCeHsNCHsCOCHs. In the "other, 'benzanilide (benzoyl anilide), the acetyl radicle is replaced by benzoyl, CeHs-NH-OCCeHs.i DIAZO COMPOUNDS. When fatty amino derivatives are treated with nitrous acid, (see p. 189), 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 be- cause they contain two nitrogen (nitrogen = azote (French)) atoms linked together. The diazo compounds are of very great importance in organic synthesis 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 or with ethyl nitrite: CeHsNHaHNOs +HNO2 =C6H5F=NNO.s +2H2O. (Benzene diazonium nitrate) ' In their passage through the animal body these drugs become partially oxidized to aminophenol CoH^x^ c;^ , which also has antip5Tetic properties, and it has been thought that it is reftUy this substance which produces the antipyretic action. On this supposition, various derivatives of par- aminophenol have been prepared and found to be equally active as antipyretics. These will be described' later on (p. 344). Acetyl paraminophenol as well as aminophenol is produced in the animal body. NITROGEN AND SUPLHUR DERIVATIVES. 335 If a diazonium salt be dried and struck with a hammer it explodes. Its most important reactions are as fol- lows: 1. With water it forms phenol and nitrogen (see exp. (2) (6) : C6H5N=NC1 +H2O =C6H50H +N2 +HC1. To obtain this result the diazonium salt is best prepared by treating a cold, acidified solution of an aniline salt with an equivalent quantity of sodium nitrite, and then boiling (see exp. 2, p. 303). 2. Boiling with alcohol causes replacement of the diazo group either by ethoxy ( — — C2H5) or hydrogen. In the first case phenyl ethyl ether or phenetole is formed : C6HsN=NCl +C2H5OH =C6H50C2H5 +N2 +HC1. In the second case benzene and aldehyde : CeHsN^NCl +C2H5OH =C6li6 +CH3CHO +N2 +H01. 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 diazo group by the halogen: CeHsN^NCl +HC1 =C6HsC] +N2 +HC1. 4. Heating with cuprous cyanide replaces the diazo group by cyanogen : CeHsN^NCl +Cu2(CN)2 =C6H5CN +Cu2<(^J^ +N2, and the resulting nitrile can be hydrolyzed to form benzoic acid (see p. 319). 336 ORGANIC CHEMISTRY. Other replacements by hydrocarbon residues, sulphur groups, etc., can also be effected. Experiments. (1) Prepare benzene diazonium ni- trate. Put 50 gm. of arsenic trioxide into a flask; pro- vide a funnel-tube, as in other gas-generators, and a delivery-tube which is connected with an empty bottle or cyUnder standing in cold water. Mix 10 gm. of aniUne nitrate with 12 c.c. of cold water in a graduate or large test-tube standing in ice-water, and immerse in the Hquid a deUvery-tube coming from the condenser- bottle of the gas apparatus. Through the funnel add 50 c.c. of concentrated HNO3 to the AS2O3; 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 ah equal volume of alcohol cooled to 0°, then some cold ether. An abundant precipitate of benzene diazonium nitrate is obtained.! Filter quickly with suction. Test for the following reactions at once : (2) (a) Dissolve some in water and let it stand. It decomposes, as is shown by change of colour, (6) Boil some with water; notice the phenol odour, (c) Boil some with alcohol in a. test-tube; it is decomposed with production of phenetole; (d) Add some to a little con- '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 HCl. Cool to 5° add 4 c.c. ethyl nitrite very slowly while shaking and cooling. Test for HNO2 with starch iodide paper. Add more ethyl nitrite if necessary. Let it stand a while, then add cold ether. NITROGEN AND SULPHUR DERIVATIVES. 337 centrated HCl and boil. Chlorbenzene 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 N2 group is replaced. Diazo compounds, however, exhibit another type of reaction in which the N2 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 amido group is replaced by a diazo residue. A type of the class is diazoaminobenzene, CeHs • N=N • NH ■ CeHs, which is prepared by bringing to- gether anihne and diazonium chloride in neutral solu- tion. It forms yellowish crystals, which are insoluble in water but soluble in alcohol. By heating with aniline, and in various other ways, diazoaminobenzene becomes converted by a rearrangement of atoms into b. Aminoazobenzene, CeHs •N=N 06114 NHa, which is the amino derivative of a substance called azobenzene. Dimethyl aminoazobenzene is CeHs •N2 -06114 •N(CH3) 2. It is used as an indicator for free acid, giving a pink colour in the presence of the latter (see p. 361) . c. Azobenzene, CeHs- N=N- CeHs. Azobenzene can be obtained by partial reduction of nitrobenzene. It forms orange-red crystals and is soluble in water, but the resulting solution is not a dye (see p. 365). The azo group is present, however, in many dyes. It has been calculated that the number of azo dyes that can theoret- ically be prepared runs up into the millions. d. Hydrazobenzene, CeHsNH — ^NHCaHs, is obtained 338 ORGANIC CHEMISTRY. by reducing azobenzene; it is colourless. Hydrazo- benzene is the diphenyl derivative of hydrazine, NH2 — ^NH2. The most important hydrazine deriva- tive is e. Phenylhydrazine, CeHsNH— NH2, which forms hydrazones (see p. 316) with aldehydes, and osazones with sugars (see p. 250). It is obtained by reduction of diazonium salts (see exp.) : C6H5N2CI+4H =C6HsNH— NH2 -HCl. (Phenylhydrazine hydrochloride) Experiment. To 18 c.c. of freshly distilled aniline add, while stirring, 100 c.c. of concentrated HCl. Cool, in a freezing mixture to 0°, add 150 gm. of ice, then add slowly, from a dropping funnel (have 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 colour) . For the test dilute a drop of the acid mixture with 5 c.c. of water. During the diazotizing the temperature must keep below 5°. Add slowly an ice-cold solution of 60 gm. of stannous chloride in 50 c.c. of concentrated HCl. Add ice to keep the temperature at 0°. Mix thoroughly and let it stand one hour. Filter through muslin, using suc- tion. Transfer to a porous plate, press out the phenyl- hydrazine hydrochloride crystals in a thin layer, and set away to dry out: 1 . CeHgNHa • HCl + HNO2 = C6H5N2CI + 2H2O. 2. C6H5N2C1 + 4H=C6H5NH.NH2-HC1. NITROGEN AND SULPHUR DERIVATIVES. 339 Free phenylhydrazine may be extracted by treating the hydrochloride with an excess of NaOH solution and shaking with ether. After dehydrating the ethereal extract, evaporate the ether; phenylhydrazine remains behind as a liquid which readily solidifies on cooling. Phenylhydrazine is a colourles«3 oil at ordinary tem- perature and boils at 242°, meanwhile undergoing some decomposition. It melts at 19°. It is poisonous. It becomes dark 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 b}' sodium acetate. By a series of reactions, which are too com- plicated for description here, a derivative of phenyl- hydrazine can be obtained which lowers fever tem- perature. This is antip3rrin or phenazone (l-phenyl-2, 3-dimethyl pyrazolone), /CO CH CeHs-N/ II \N(CH3)— C— CH3 It is really a heterocyclic compound (p. 373). It acts as a weak base, certain of its salts being used medicinally, e.g., tussol, which is antipyrin mandelate. The relationship of these bodies to nitrobenzene and aniline will be evident from an examination of the following formulae : CeHs-N CeHs-NH CeHg-NH C6H5NO2 II I I CeHsNHz '^ie^er' CfiHs-N CsHs-NH NH2 <^°"'°«> (Azoben- (Hydrazo- (Phenylhydrazine) zene) benzene) 310 ORGANIC CHEMISTRY. SULPHUR DERIVATIVES. Sulphonic acids. With sulphuric acid the benzenes form sulphonic acids, thus : C6H6 + H2S04=C6H5S03H+H20 (Benzene-sulphonic acid) and C6HgCH3+H2S04=C6H4<|Q^^jj+H20. (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 other 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 pentachloride the salts of sulphonic acids form sulphonic chlorides, which may be reduced to mercaptans : 1. CeHsSOaNa +PCI5 =C6H5S02C1 +POCI3 +NaCl. 2. C6H5SO2CI +6H =C6l^5SH+HCl+2H20. (Thiophenol) These reactions show us that sulphonic acids must possess an — OH group and that the S atom is in imme- diate connection with the benzene ring. The structural formula of benzene-sulphonic acid must therefore be TTQ °\o n ) °^ sulphuric acid, TT(-)ySC)2, in which one hydroxyl group is replaced. by phenyl (c/. p. 194). AROMATIC SULPHUR DERIVATIVES. 341 They give several other reactions, the following of which are important : 1. Fused with potassium hydroxide, benzene-sulphonic acid yields phenol, CeHsSOsK + KOH = CeHgOH + K2SO3. Experiments. (1) To 75 gm. of fuming H2SO4 in a small flask to which an air-condenser is attached, add, a little at a time, 20 gm. of benzene, shaking and cool- ing 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 ben- zene 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 centimetres of water, and melt. Then add slowly, while stirring with a spatula, the sodium ben- zene sulphonate. Keep fused for an hour. Dissolve in water, acidulate with HCl, shake with ether, and treat the ethereal solution of phenol in the same way as in the previous phenol experiments (see p. 303). 2. Distilled with potassium cyanide, cyanides are formed : C6H5SO3K + KCN = CeHsCN + K2SO3 and C6H4<^q^'k + ^^^ = ^6H4C0+CaC03. CeHslCqO / i CeHs^ (Benzophenone) b. By distilling salts of two different aromatic acids such as a salt of benzoic and one of toluic acid: n Tj /CHs p, TT /CH3 O6tl4\Q00M 1 ^6-tl4\(.Q + = / +M2CO3. CeHsCOOM CeHg (Phenyltolylketone) ' The salt usually employed is that of calcium. M means a metal, 364 ORGANIC CHEMISTRY. c. By distilling a salt of an aromatic acid with one of a fatty acid : CeHgCOOM CeHsK + = >CO+M2C03. CH3COOM CH3 / (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. Quinones. These may be regarded as diketones.^ The best known of them is benzoquinone or quinone, /■% HC CH which has the structural formula || || , and HC CH \co/ may be prepared by oxidizing various para derivatives of benzene, but not ortho or meta derivatives. Thus p-phenolsulphonic acid, p-sulphanilic acid, p-amido-. phenol, etc., all yield quinone when oxidized. It is usually prepared, however, by oxidizing aniline with chromic acid or by oxidizing hydroquinol: ' These do not strictly belong to the class of bodies that we are considering as mixed compounds. MIXED AROMATIC COMPOUNDS. 365 COH C=0 /\ /\ HC CH HC CH 1 +0 = = II II +H2O. HC CH HC CH \/ \y- COH C=0 These reactions for its preparation (with the excep- tion of its preparation from anihne) leave little doubt as to its structural formula. The quinones are of a yellow colour and possess a pungent odoiu". They have oxidizing properties and are important in dye chemistry. Several dyes have already been mentioned. All such bodies are supposed to owe their dyeing properties to the presence in them of a so-caUed chromophore group. Chromophore groups are of various kinds, of which the following are important : 1. The azo group N=N, as in orange II (see p. 357). 2. The nitro group NO2, as in picric acid (see p. 306)- 3. The group C-(R)-N, as in methyl violet (see p. 332). I. 1 4. The group (R)<^qq^(R), as in alizarin (seep. 371). The presence in a substance of one of these groups alone is not, generally, sufficient to constitute it a dye; certain other groups, such as OH and NH2, must, as a rule, be attached to a chromophore-containing com- pound to render it available as a dye. These assisting or auxihary groups are called auxochromes. The chemistry of the cause of colour in organic compounds is being vigorously investigated; as a result it will 366 ORGANIC CHEMISTRY. not be surprising if the above theory is soon cast aside. The sulpho group is often introduced to render a dye soluble. For many dyes a mordant is necessary, that is, an agent that will fix the colouring matter in the fibres of the fabric. 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 oxide of the metal; the dyeing con- sists in forming an insoluble compound of the coloured substance with the oxide. 12. Benzene derivatives having unsaturated carbon Unkings in a side chain. Cinnamic aldehyde has the formula CeHg— CH=CH— CHO. The corresponding acid is cinnamic acid, CeHs • CH=CH • COOH. The alde- hyde is the essential constituent of cinnamon oil. Syn- thetic cinnamic aldehyde is now displacing natural oil of cinnamon. Ciimamic acid is a therapeutic agent. Other allyl derivatives of benzene are eugenol and safrol. Eugenol, or parahydroxy-metamethoxy-allyl-ben- /C^Ha— CH=CH2 HC/ ^CH zene, II | , is the chief substance HC\ yCOCHs in oil of cloves, and is contained in other drugs. Eugenol acetamide, eugenol carbinol, eugenol iodide and benzeugenol have been put on the market as me- dicinal preparations. Safrol is contained in oil of sassafras and camphor MIXED AROMATIC COMPOUNDS. 367 oil. It is the methylene ether of allyl pyrocat- ■ echol. yCH2-CH=CH:. (1) ^^^'\0/*^^2 (3 and 4). Apiol has the same formula as safrol, except that it has OCH3 groups in the place of H in positions 2 and 5. CHAPTER XXX AROMATIC COMPOUNDS HAVING CONDENSED RINGS. Kaphthalene (CioHg) contains two benzene rings connected together in the following manner: CH CH r • HC A' 2 CH HC 5 V A 3 CH >/ A*/ M CH It forms white crystals melting at 79.6°, boiling at 218.1° and having a tar-like odour. It is volatile and is contained in coal-gas, being also a constituent of the distillate from coal-tar. Experiments. (1) Heat some.naphthalene in a sub- limation apparatus. (2) Try the reaction with aluminium chloride given by some naphthalene dissolved in chloroform (see p. 296). The naphthols, CioHj-OH, coiTespond to phenols. Alpha-naphthol (melting-point 95°) and beta-naphthol (melting-point 122°) are both of importance, a Deriva- tives of naphthalene have some group introduced in position 1, 4, 5 or 8, while /9 derivatives have it in 368 NAPHTHALENE AND DERIVATIVES. 369 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 in positions 1, 2, 3, 4). Epicarin is /3-naphthol-ortho-hydroxy-toluic acid, /COOH CeHs^OH \CH2 • OC10H7 /?-naphthol benzoate, C10H7 — OOC-CeHs, is another of the newer remedies. Orphol is a combination of beta-naphthol with bis- muth nitrate. All these substances are antiseptics. Alpha- and beta-naphthylamines, CioH7-NH2, are used as reagents. a-Naphthylamine. is used to detect the p'*esence 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 ^^°J>CioH5 • N=N ■ C6H4 • C6H4 • N=N ■ CioH6<|O^^J^^ Its colour becomes blue in the presence of free acids. It forms a colloidal solution, which will not dialyze. Electrolytes cause its molecules to aggregate. Santonin, CigHigOs, is* a derivative of naphthalene and is the anhydride or lactone of santoninic acid. Its formula is probably, 370 ORGANIC CHEMISTRY. oc C — CH3 CH2 c IsC c \/\y C — -CHa CH2 CH CH 0, CH-CH3 Elaterin, a neutral principle, is said to be a derivative of naphthalene. Anthracene. C14H10, is a hydrocarbon containing three benzene rings condensed together: 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 dianthra- cene, this depolymerizes in the dark to anthracene, a reversible photo-chemical reaction: 2Ci4Hio<=^C28H20. ANTHRACENE AND DERIVATIVES. 371 One of the important derivatives of anthracene is anthraquinone, CH CO HC HC / CH s/^\/^^X. 9- CH CH , C14H8O2. CH CO CH Dihydroxyanthraquinone is the very important dye alizarin, Ci4H602(0H)2: HC HC CH CO COH f CH 'C c\ CO CH COH ^H Aloin is an anthraquinone derivative, its formula may be (the position of the OH being uncertain): CH CO C-OH C /\ C C- — CH3 c \/ c \/ /^^' CH CO C— 0— CH(CH0H)3CH0 37: ORGANIC CHEMISTRY. Chrysophanic acid, Ci4H502(CH3)(0H)2, and chrysa- robin, C15H12O3, are anthraceae derivatives of thera- peutic importance, chrysophanic acid probably being monomethyl-dihydroxy-anthraquinone, and chyrsarobin monomethyl-trihydroxy-anthracene. Emodin, C15H10O5, is a 2-mononiethyl 3, 6, 7-tri- hydroxyanthraquinone. Rhein, CisHgOe, is also an anthraquinone derivative, /COOH (1) Ci4H502^0H (3) . \0H (5) Isomeric with anthracene is phenanthrene, C14H10: OH CH HC CHAPTER XXXI. 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.^ Pyrrol has the formula HO — CH. lodol is a medicinal II II HC CH \/ NH derivative, it is tetraiodopyrrol. Pyrrolidine is the hydrogen addition derivative of P5Trol, H2C— — CH2. This is the basis of certain alka- loids. a.2C\\'/Gn.2 NH Prolin and hydroxy-prolin are pyrrolidine acids (p. 216). ' Heterocyclic compounds of minor importance are thiophene, HC-CH and pyrazole, HC CH \/ S HC— CH I I HC NH \/ NH 373 374 ORGANIC CHEMISTRY. Hsematin, hsemin, and haematoporphyrin (from haemo- globin) are supposed to contain four pyrrol rings in their molecules. Pyridine Bases. These are ammonia derivatives and of great importance on account of their relationship to certain alkaloids which will be discussed presently. The simplest member of the series is pyridine, which has the CH structural formula HC N . It may therefore be CH considered as benzene with a CH group replaced by nitrogen (CsHsN). 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, am- monia, methylaminc, etc. Pyridine is a colourless liquid with an odour like tobacco-smoke. It boils at 115° C. It mixes readily with water, the resulting solution being strongly alka- line. Like other tertiary ammonia bases, it directly combines with acids to form crystalline salts. When warmed with alkyl halides addition products are formed, and if these be treated with caustic potash a very pun- gent and disagreeable odour is evolved. Experiments. (1) Dissolve some pyridine in water; test alkahnity with Utmus. Notice the odour. (2) Then neutralize the solution with HCl, add a few drops of platinic chloride solution, and boil; a yellow precipitate of (C5H5N)2PtCl4 forms. HETEROCYCLIC COMPOUNDS. 375 CONDENSED HETEROCYCLIC BENZENE COMPOUNDS. PYRROL DERIVATIVES OF BENZENE. Indol, C6H4<'.njTT^CH, contains the pyrrol nucieus, condensed with the benzene nucleus, and may be represented thus: CH CH HC C CH HC or CH B \ C K CH NH \!. CH CH IH NH Skatol is methyl indol, C6H4^ \1N ./CH3 JCH. Indol ^NH/^ and skatol are contained in faeces, imparting the char- acteristic odour to the latter. They are produced 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 combina- tion with sulphuric acid as an ethereal sulphate, /C-O-SOaCOH) Q jj^/ ^^CH ■ It is indoxyl-sulphuric •\nh/ acid. It is sometimes present as a potassium salt in the urine in considerable quantity. The urine may also contain indoxyl glycuronic acid. The origin of these bodies is indol absorbed from the bowel-contents. 376 ORGANIC CHEMISTRY. Indigo can be obtained from it, and occasionally indigo is deposited 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 colourimetric estimation may be made. Skatoxyl-sulphuric acid is the corresponding derivative /Cs-CHs of skatol, CsHZ >C— 0— S02(0H). y C ^^Ha • CH (NH2) ■ COOH /3-indol a-amino-propionic acid. It is a decomposition product of protein, being produced during tryptic digestion. It, in turn, is attacked by bacteria, giving rise to indol. It gives a colour reaction with glyoxyhc acid (see p. 204). Directly related to indol is isatin, C6H4/^Vr\;!0, dioxyindol, for the former can be obtained from the latter by reduction. Indigo, structurally, is a combina- tion of two isatin molecules, the end oxygen atom of each molecule being ehminated, thus : Tryptophan, CeHX >CH is CeHC^CCe 1H4 Indigo can be produced from isatin. It is a valuable blue dye. The synthesis of indigo on a commercial scale is one of the great achievements of chemistry. HETEROCYCLIC COMPOUNDS. 377 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. Naphthalene is the starting-point of the synthesis. This is oxidized by ftuning H2SO4 to phthahc acid, the latter is converted into phthalimide, by treatment with chlorine and soda; this becomes anthran- ilic acid. This acid is condensed with chloracetic acid, giving — CO PH rOOH" -fusion with KOH NH converts this into indoxyl, and the latter is oxidized to indigo by exposure to the air. In plants the indigo is contained in a glucoside com- bination. Reduction (adding H) changes indigo to indigo white; it is in this form that it is introduced into cloth for dyeing. Indigo red, indirvbin, 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 ortho- nitrobenzaldehyde, warm the mixture in a bath kept at 50° for ten minutes. Cool, add a few drops of 10% NaOH and shake. A yellow colour appears first', then a green. When 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, 378 ORGANIC CHEMISTRY. 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 byN: CH CH Hc/^r'AcH HC ,CH , C9H7N. It is \/c\/ CH^N 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 concentrated sulphuric acid (see exp. below) : PTT ntT CH CH + CHOH 4-0= +4H2O I HCl /. iCH VCXNH, CH,OH \/cY (Aniline^ (Glycerol) (Quinoline) CH HC HC CH Quinoline is a liquid boiling at 237°. By proper treatment of quinoUne, pyridine can be derived from it. Many alkaloids are quinoline derivatives. Oxyquinoline Sulphate (chinosol), (C9H7NO)2H2S04, is a substance used as an antiseptic, and is said to be non-toxic. HETEROCYCLIC COMPOUNDS. 379 Experiment. Synthesize quinoline. In a litre flask mix 15 gm. of nitrobenzene, 24 gm. of aniline, and 75 gm. of glycerol; add 62 gm. of C.P. H2SO4 while agitat- ing 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 distil with steam. When no more oily drops of nitro- benzene come over, stop the distilling. Cool par- tially, render the mixture alkaline with strong NaOH solution, and again distil with steam, thu"? removing the quinoUne and aniline. This last distillate is specially treated to convert the anihne into phenol, as was di- rected in the experiment under phenol (see p. 259). Diazotize the cooled liquid after rendering it distinctly acid with dilute H2SO4, warm in a bath, make alkahne (the phenol becomes fixed as a phenolate, while quino- line is set free), and distil with steam. Extract the quinoline from the distillate with ether and proceed just as was done with phenol. ThaUine, C9H9(OCH3)NH, and Kairine, C9H9(OH)N — C2H5, are quinoline derivatives that have been used as antipyretics. Analgen (quinalgen) is a more recent antipyretic, CflH5(OC2H5)NH(COC6H3)N. Kynurenic acid, occurring in the urine of dogs, is a quinoline derivative, 380 ORGANIC CHEMISTRY. CH COH HC/^'^S^C—COOH; CH N it is supposed to be derived from tryptophan. Isoquinoline, C9H7N, is an isomer of quinoline: 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. . Ethereal salts. a. Phenols • (1) Monacid phenols (Substitution (. products. (2) Diacid phenols. (3) Triacid phenols. (4) Hexacid phenol derivative. SYNOPSIS OF AROMATIC COMPOUNDS. 3S1 b. Fatty alcohol side-chain compounds and derivar Alcohols (primary). Aldehydes. Monobasic acids ■!„,," , ( luhereal salts. tives 3. Dibasic acids. 4. Nitrogen derivatives. (a) Nitro compounds. (6) Amino compounds, (c) Diazo compounds. 5. Sulphur derivatives. 6. Mixed compounds. (1) Phenol and sulphonic groups. (2) Phenol and nitro groups. (3) Phenol and amino groups. (4) Phenol and primary alcohol groups. (5) Hydroxy-acids. (6) Hydroxyl groups and fatty acid side chain. (7) Acid and nitro groups. (8) Acid and amino groups. (9) Acid and sulpho groups. (10) Sulphonic and amino groups. (11) Ketone linkings and quinones. (12) Unsaturated side-chain combinations with ben- zene derivatives. B. Condensed benzene kings. 1. Naphthalene. 2. Anthracene. 3. Phenanthrene. C. Heterocyclic compounds. 1. Pyrrol and pyridine bases. 2. Condensed heterocyclic-bemene rings, (1) Indol and derivatives. (2) Quinoline and derivatives. (3) Isoquinoline and derivatives. (4) Alkaloids. CHAPTER XXXII. 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 theobro- mine, purin bases and other leucomaines, choline, mus- carine, and other ptomaines are all called alkaloids. Most alkaloids are tertiary ammonia bases. The most recent definition which seems acceptable is that alkaloids include all nitrogenous plant products which have N in a closed chain of atoms. Those whose structure is known are derivatives of pyridine, pyrroli- dine, quinoline, isoquinoline, phenanthrene or purin. The empirical formulae of the chief alkaloids are as follows : Coniine CgHirN. Nicotine C10H14N2. Sparteine C15H26N2. Theobromine C7H8N4O2. Theophylline CyHgNiOa. Caffeine C8H10N4O2. Pelletierine CgHieNO. Pilocarpidine C10H14N2O2. Hydrastinine CnHisNOs. 382 ALKALOIDS AND DRUG PRINCIPLES. 383 Pilocarpine C11H16N2O2. Physostigmine C15H21N3O2 (Eserine). Eseridine C16H23N3O3. Homatropine . . . . C16H21NO3. Sinipine C16H25NO6. Apomorphine Ci7Hi7N02. Piperine C17H19NO3. Morphine C17H19NO3. Cocaine C17H21NO4. Hyoscine , C17H21NO4 (Scopolamine). Atropine C17H23NO3 ] , TT • n Tj -KJi^ ^Isomers. Hyoscyamine O17H23NO3 J Codeine C18H21NO3. Lobeline C18H23NO2. Thebaine C19H21NO3. Cinchonine C19H22N2O ] Cinchonidine C19H22N2O J Curarine C19H26N2O. Sanguinarine C2o^Hi5N04. Berberine C20H17NO4. Papaverine C20H21NO4. . Quinine C20H24N2O2 (Isomer,Quinidine) Hydrastine .... C21H21NO6. Strychnine. C21H22N2O2. Narcotine . ... C22H23NO7. Colchicine C22H2SNO6. Gelseminine C22H26N2O3. Yohimbine C22H28N2O3. Brucine C23H26N204. Narceine 0231127^08. Jervine C26H37N03. Emetine 0:0^^40^205. 3S1 ORGANIC CHEMISTRY. Veratrine C32H49NO9. Aconitine C34H47NO11. Ergotinine C35H39N5O5. Ergotoxine C35H41N5O6. Coniine and nicotine are the only important alkaloids that contain no oxygen and that are volatile liquids- Sparteine, pelleteirine and pilocarpidine are liquids, but non-volatile. All of the alkaloids form salts with acids (see p. 187); 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 immiscible solvents — ether, chloroform, benzene, and amyl alcohol.. All alkaloids are precipitated by phosphomolybdic and phosphotungstic acids, most of them by potassium mercuric iodide and many of them by tannic acid. Most of the alkaloids are optically active, generally laevorotatory. Many of the alkaloids are extremely poisonous, but in minute doses they are very valuable remedies. The alkaloids here considered are of vegetable origin, practically all coming from dicotyledonous plants. We shall consider now some of the facts tha,t are known in regard to the structm-e of alkaloids. PYRIDINE DERIVATIVES. It is necessary to designate the positions of groups in the pyridine ring thus : CH(r) (^')HC/^CH(/?) (a')HC N CH(a) ALKALOIDS AND DRUG PRINCIPLES. Piperidine is the simplest derivative, 385 H2C H2C CH2 NH CH2 CHa' Piperme is contained in pepper. It is a combination of piperidine and piperinic acid. Coniine is dextro-a-propyl piperidine, CH2 H2C/\CH2 H2C CH — CH2 ■ CH2 • CH3 NH Nicotine is a pyrrol derivative (see p. 373) of pyridine the attachment of methyl pyrrolidine to pyridine being in the j3 position of the latter and position 2 of- the former: CH HCA^ H2C HC N HC\/ CH N I GH, CH2 CH2 Coniine and nicotine have marked similarities; both are volatile liquids having a strong odour, and both are very poisonous. Coniine is obtained from hemlock-seed, and nicotine from tobacco. Both are strongly alka' 386 ORGANIC CHEMISTRY. line to litmus. In tobacco the nicotine is combined with malic acid and citric acid. Synthetic 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 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 determined It is dextrorotatory. The artificial alkaloids a- and /?-eucaine are complex piperidine bodies. v CeHsCOO^C/OOC-CHs CeHsCOO^c.-H .A HoC HsCs N CH2 /CII3 'H3 H2C H3C HoC CH, ^v< H CH3 CH3 (a-eucaine) H (;9-eucaine) The eucaines are local anaesthetics, and differ from cocaine in action'in that they do not affect the pupil. Euphthalmine is related to /?-eucaine, having a CH3 group in place of the H attached to N and having the ALKALOIDS AND DRUG PRINCIPLES. 387 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 oi the cocaine and atropine group are all pyrrolidine derivatives. This class of alkaloids is of great pharmacological importance. Cocaine is an in- valuable local anaesthetic, while members of the atro- pine group are used to dilate the pupil. The basal substance for all of these compounds is tropine. This has, as will be noticed, a secondary closed carbon chain : HoC HC H»C CHOH CHa CH Cfl, This double ring nucleus is called the tropan nucleus. It may be looked upon as a condensation of the pyrrol with the pyridine ring, having N and the two neighbor- ing C atoms in common to the two rings. 388 ORGANIC CHEMISTRY. Tropic acid has the formula r TT PTT/CH2OH O6XI5 — ^•'^\C( \COOH • Atropine is the tropine ester (tropine being an alco- hol) of tropic acid, its formula being HC CH, CH CH, H.C CHaOH Cell 6 Atropine is optically inactive. Its physiological action is what would be expected of d Z-hyoscyamine. Hyoscyamine is Isevorotatory. 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, CH3 and NO3 attaching to the N atom of atropine, the latter changing its valence to five. It is used ALKALOIDS AND DRUG PRINCIPLES. 389 for the same purposes as atropine, but is much less toxic. Homatropine 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. Hyoscine and scopolamine are esters also, consisting of tropic acid combined with scopolin, C8H13NO2, an alcohol derived from pyrrolidine. They are iso- meric, hyoscine being Isevorotatory and scopolamine racemic. If in tropine an H atom of a CH2 group of the secondary ring be replaced by COOH, ecgonine is obtained : H.C HC CH, HoC CHOH COOH From this is derived cocaine, which is the methyl ester of ecgonine benzoate: 390 ORGANIC CHEMISTRY. HjCi |CH, lie HjC CH, CH ~COO-CH, OOC-CeHs Cocaine exists both as d and as I, 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 chem- ical structure, there are some resemblances in phar- macological action. Tropacocaine has a formula similar to cocaine, but having CH2 instead of CH-COOCHs. It is less toxic and as strongly anaesthetic as cocaine. It has little effect on the pupil. QUINOLINE DERIVATIVES. The chief alkaloids of this class are the cinchona alka- loids. The following formula has been suggested for cinchonine : ALKALOIDS AND DttVG PRINCIPLES. CHa^CH— CH— CH— CH2 CH2 CH2 H2C — N CH 391 CHOH CH (X) HC HC. \V c CH CH \/c\. CH N Quinine has the same formula, except that an H atom .at the position marked (X) is replaced by the methoxy group (OCH3). Cinchonine is dextrorotatory, quinine Isevorotatory. Cinchonidine is the Isevorotatory isomer of cinchonine. Quinidine is the dextrorotatory 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. Quinine urea hydrochloride, a crystalline double salt, is very soluble and is suitable for subcutaneous in- jection, being non-irritating and even anaesthetic locally. Strychnine and brucine are believed to be quinoline derivatives, but their structure has not been fully worked out. The nature of the nitrogen Hhkings is known. Strychnine may be represented as 392 ORGANIC CHEMISTRY. (C2oH220)^CO Brucine differs from it in having two methoxy (OCH3) groups in the place of two-hydrogen atoms: (C2oH2o(OCH3)20)^— CO Both strychnine and brucine are Isevorotatory. Strych- nine is much used as a medicine, brucine not at all. Methyl strychnine is obtained as follows: strychnine is treated with methyl iodide; an addition compound is formed, C2iH22N202-ICH3, the N atom which has the triple bond changing its valence from III to V in order to attach the I and CH3; when this is treated with silver sulphate and barium hydroxide solution the product is the ammonium base, C2iH22N202-CH3(0H); on standing this becomes methyl strychnine, (C20H220)< \^\ t\co/' \nh Dimethyl strychnine hss the same formula, except that CH3 is substituted for H in the NH group. This is produced from methyl strychnine in exactly the ALKALOIDS AND DRUG PRINCIPLES. 393 same manner as the latter is derived from strychnine; in this case, however, no oxygen is introduced into the molecule, but only CH3. ISOQUINOLINE DERIVATIVES. The minor o'pium alkaloids, papaverine, narcotine, and narceine, also hydrastine and berberine, belong to this group. These alkaloids are of very Uttle impor- tance (except hydrastine) therapeutically. Papaverine has the simplest structure; it is tetramethoxybenzyl- isoquinoline; its formula is 0— CH3 H3CO— C H3CO-C /^V^x. V* CH Papaverine has been synthesized. 394 ORGANIC CHEMISTRY. Hydrastine has a similar but more complicated struc- ture : OCH3 I C HC HC y C— OCH3 C CO (X) CH C CH- I CH -0 .0_G/ /\. c ./\ H.C Narcotine is methoxyhydrastine, the OCH3 group taking the place of H at (X). Hydrastinine is an alkaloid prepared by oxidation of hydrastine with nitric acid. It has a much stronger physiological action than hydrastine. Its formula is CH /O— C'^ H2C \o— c, CH CH2 CH=0 NH— CH3 CH2 ALKALOIDS AND DRUG PRINCIPLES. 395 the side chain being bent so as to point out its derivation from hydrastine. Narceine has a somewhat similar formula, but it has a benzoic acid group and several methoxy groups, additional. Berberine has a still more complex formula. Cotamine, C12H15NO4, is an oxidation product of narcotine, as hydrastinine is of hydrastine. Its for- mula corresponds to the isoquinohne half of the narcotine formula. Its hydrochloride is called stypticin, the phthalate is called stjrptol. Cotamine and hydrastinine have very similar phys- iological action; both affect the circulatory system in such a way as to lessen haemorrhage. Cotamine is much less expensive. PHENANTHRENE DERIVATIVES. These are morphine, codeine, and thebaine, all of them being alkaloids present in opium. Derivatives of mor- phine artificially produced are apomorphine, dionine, heroine and peronine. Morphine is the most valuable alkaloid for therapeutic purposes that we have. Opium contains about ten per cent of morphine. Its derivatives are much weaker in physiological action. Its Constitutional formula is now believed to be: ORGANIC CHEMISTRY. C-OH (X) Codeine has the above formula, with CH3 substituted for the H of the OH group at X. Thus codeine is the monomethyl ether of morphine. Codeine' has been prepared from morphine by treating the latter with methyl iodode in the presence of caustic potash: Ci7Hi7NO(OH)2 + CH3l + KOH (Morphine) =Ci7Hi7NO(OH) (OCH3) + KH- H2O. (Codeine) ' It is prepared commercially by heating a mixture of morphine and potassium methyl sulphate (K(CH3)S04) with alcohoUc KOH (see exp.). ALKALOIDS AND DRUG PRINCIPLES. 397 Both morphine and codeine are Isevorotatory. Thebaine has two less hydrogen atoms attached to the phenanthrene nucleus, and has two OCH3 groups in place of the two hydroxyls of morphine. By the action of concentrated mineral acids, a mole- cule of water can be removed from morphine, producing apomorphine : C17H19NO3— H2O =Ci7Hi7N02. (Morphine) (Apomorphine) It is supposed that in apomorphine the phenanthrene 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, CitHitNOCOH) (OC2H5) • HCl. Heroine is an ester, diacetate of morphine, Ci7Hi7NOH HC— N^ It is dextrorotatory. It has a marked pharmacological -action. CERTAIN ALKALOIDS THAT HAVE NOT BEEN CLASSIFIED. The following indicates what is known about the structure of aconitine: C2iH27(0CH3)4(N05) Formic acid 0.547 0.00532 Acetic acid . ... 0.000747 Monochloracetic acid Dichloracetic acid 0.0295 0.245 Trichloracetic acid 0.670 0.169 Succinic acid 0.00195 Citric acid 00797 INDEX Absolute alcohol, 118 Aoetaldehyde, 127 Acetaldehyde cyanhydrin, 123 Acetamide, 219 Acetaminophenetole, 344 AcetamHde, 333 Acetates, 142 Acetic acid, 137 " ", freezing-point ta- ble, 408 ", glacial, 139 " " metaUic salts, 142 " " , mol. wt. determi- nation, by silver salt, 76 " " , proofs of structural formula, 140 " " , specific gravity ta- ble, 408 " tests, 140 Acetic anhydride, 145, 179 Acetic ether, 155 Aceto-acetic acid, 166, 202 Acetone, 164, 296 Acetonitrile, 184 Acetophenone, 364 Acetozone, 316 Acetphenetidin, 344 Acetylation, 145, 179 Acetyl chloride, 143 Acetylene, 273 Acetylenes, 268, 273 Acetyl group, 143 " paraminophenol, 334 ' ' paraminophenyl saUcy- late, 349 ' ' saUcylic acid, 349 " value, 179 Achroodextrin, 264 Acid amides, 92, 218 " chlorides, 143 " imides, 229 " strength, estimation of, 159 " value, 178 Acids, 90 " , aromatic, 318 ' ' , dibasic aromatic, 324 " , fatty, 133 " , monobasic aromatic, 318 " , monobasic, dibasic, etc., 90 " , strength of, 148 Aconitine, 384, 399 Acrolein, 271 Acrylic acid, 271 Acrylic aldehyde, 271 Acyclic compounds, 93 Acyl halogenides, 143 Adenin, 238 Adrenalin, 353 Adsorption, 71 Agar-agar, 265 Agaric acid, 210 411 412 INDEX. Agaricinic acid, 210 Aggregates of molecules, 64 Airol, 352 Alanin, 213, 249 Alcohol, absolute, 118 ' ' , denatured, or methylat- ed, 118 ' ' , heat of combustion, 113 " , ordinary, 118 " , specific gravity tables, 403 Alcohols, 87 ' ' , aromatic, 314 ' ' , diacid, 167 ' ' , monacid, diacid, etc.89 " , monacid primary, 114 " , oxidation products of, 89 ' ' , primary, 87, 112 ' ' , secondary, 87, 163 " , tertiary, 88, 166 , triacid, 173 Aldehyde, 127 acid, 203 " ammonia, 123 " bisulphite, 123 ' ' group, 89 " tests, 123, 129 Aldehydes, 89, 122 " , aromatic, 314 Aldohexose, 246 Aldol, 127 Aldol condensation, 247 Aldose, 244, 246 Aliphatic division of organic chemistry, 81 AHzarin, 371 Alkaloidal precipitants, 384 Alkaloids, 382 Alkyl cyanides, 185 " hydroxides, 112 " haUdes, 101 Alkyls, 86 Allantoiin, 236 Alloxan, 231 AUoxuric bodies, 238 AUyl alcohol, 271 " isothiocyanate, 273 " radicle, 271 " sulphide, 272 ' ' sulphocarbamide, 273 " thiourea, 273 Aloin, 371 Alpha naphthol, 368 Alpha naphthylamine, 369 Alphozone, 172 Alypin, 322 Amido acids, 211 Amido group, 92 Amines, 186 Amines, mixed ai-omatic fatty, 332 Aminoacetic acid, 213 Aminoacetphenetidin, 344 Amino acids, 92, 211, 249 Anfinoazobenzene, 337 Aminobenzoic acids, 322 Amino compounds, aromatic, 329 p-Aminoethylsulphonic acid, 217 Aminoformic acid, 211 a-Aminoglutaric acid, 214 Aminohexose, 248 a-Aminoisobutylacetic acid, 214 Aminophenols, 334, 343 a-Aminopropionic acid, 213 Aminosuccinic acid, 214 Aminovaleric acid, 214 Ammonia derivatives, 91 Ammonium carbamate, 211 Ammonium cyanate, 224 Amphoteric electrolytes, 213 Amphoteric reaction, 362 Amygdalin, 266, 315 Amyl alcohol, fermentation, 120 " " , inactive, 120 " " , normal, 120 Amylene hydrate, 121 Amyl nitrite, 193 Amylodextrin, 264 Amylopectin, 264 Amyloid, 261 INDEX. 413 Amylose, 264 Amylum, 263 Amyl valerate, 162 Anaesthesin, 349 Anaesthetics, 102, 105, 110 Analgen, 379 Analysis, elementary, 25 Anhydrides, 145, 171, 324 Anhydrolysis, 184 Anilides, 333 Aniline, 329 " derivatives of, 331 " salts, 329 Anions, 58 Anisole, 305 Anozol, 108 Anthracene, 370 Anthracene oil, 283 Anthranilic acid, 355 Anthraquinone, 371 Antifebrine, 333 Antikamnia, 333 Antinosin, 325 Antipyretics, 333, 344 Antipyrin, 339 Antipyrin mandelate, 339 Apiol, 367 Apomorphine, 383, 397 Aqueous pressure, 408 Arabinose, 245 Arachidic acid, 162 Arbutin, 266 Arginase, 216 Arginin, 215 Aristol, 309 Aromatic acids, 318 " alcohols, 314 " amines, 329 ' ' bases having nitrogen in nucleus, 374 " compounds, 81, 93, 281 ' ' compounds, having condensed rings,368 ' ' compounds, mixed, 343 Aromatic compounds, synopsis of, 380 " " , reactions of, 282 ' ' hydroxy compounds, 301 " ketones, 363 ' ' nitrogen derivatives, 327 ' ' sulphur derivatives, 340 Arsacetin, 345 Arsanilic acid, 345 Arseno-benzol, 344 Arsine, substitution derivatives of, 192 Asparagin, 222 Asparaginic acid, 214 Aspartic acid, 214 Aspirin, 349 Association of liquids, 60 Asymmetric N atom, 200 Asymmetric carbon atom, 200 Atomic weight of elements in organic compounds, 2 Atoxyl, 345 Atropine, 388 Autocatalysis, 203 Auxochromes, 365 Avogadro's hypothesis, 37 Azobenzene, 337 Baeyer's reagent, 270 Baking powder, 207 Ballistite, 175 Balsams, 320 Balsam of Peru, 320 " ofTolu, 320 Barfoed's reagent, 256 Barometer, correction for tem- perature, 19 Bases, strength of, 149 Bassorin, 265 Beckmann's thermometer, 52 Beer, see Malt liquors. Beet sugar, 258 414 INDEX. Behenic acid, 162 Benzal chloride, 316 Benzaldehyde, 315 Benzamide, 323 Benzanilide, 334 Benzene, 283 " derivatives, 93, 282 " diazonium nitrate, 334 ' ' diazonium sulphonic acid, 357 " , disubstitution prod- ucts of, 291 ' ' , homologues of, 294 model. Collie's, 288 ' ' , preparation of, 284 " , ring, 287 " , structure of, 285 ' ' sulphonic acid, 340 " trisubstitution deriva- tives, 293 Benzeugenol, 366 Benzine, 98 Benzoates, 320 Benzoic acid, 294, 318, 335 " " , preparation o f , 320 " " , salts of, 320 " " , substitution prod- ucts of, 321 Benzoic aldehyde, 315 Benzoin, 316 Benzol, 283 Benzonitrile, 335 Benzophenone, 363 Benzoquinone, 364 Benzosol, 310 Benzosulphinide, 355 Benzotrichloride, 319 Benzoylacetyl peroxide, 316 Benzoylaminoacetic acid, 322 Benzoyl anilide, 334 Benzoyl chloride, 319, 321 Benzoylation, 154, 321 Benzozone, 316 Benzyl acetate, 314 Benzyl alcohol, 314 Benzyl chloride, 299 Benzyl methyl ether, 314 Berberine, 395 Betaine, 190 Beta naphthol, 369 Beta naphthylamine, 369 Betol, 350 Bicyclic compounds, 275 Biological methods, for testing molecular concentration, 47 Biose, 242 Bitter almonds, oil of, 315 Biuret, 226 Biuret reaction, 226, 241 Bleier and Kohn, vapour den- sity determination, 39 Blood, depression of freezing point, 58 BoiUng-point determination, 17 " at 760 mm., 18 Borneol, 278 Boyle's law, 37 Branched chains, 84, 99 Brandy, 116 Brombenzene, 298 Brometone, 165 Bromoform, 106 Bromural, 228 Brucine, 392 Butane, 82, 97 Butter, 177 Butyl alcohol, normal, 120 Butyl chloral hydrate, 132 Butyric acid, 160 Butyrin, 160, 174, 176 Butyrolactone, 203 Cacodylic acid, 193 Cadaverine, 192 Caffeine, 237, 382, 399 Camphor, 278 , artificial, 277 " , monobromide, 279 , oil, 366 Camphoric acid, 278 Camphors, 278 INDEX. 415 Cane sugar, 256, 258 Cantharidin, 399 Caoutchouc, 280 Capric acid, 162 Caprin, 176 Caproic acid, 162 Caproin, 176 Caprylic acid, 162 Caprylin, 176 ■Caramel, 268 Caraway, oil of, 309 Carbamic acid, 211 Carbamide, 222 Carbinol, 114 Carbohydrates, 243 Carbolic acid, 302 Carbolic oil, 283 Carbon atom, asymmetric, 200 ' ' , detection of, 3 ' ' , estimatiom of, 25 " , oxy chloride, 105 ", tetrachloride, 97 Carbonyl group, 90 Carboxyl group, 90 CarboxyUc acids, 133 Carnitine, 190 Carvacrol, 278, 308 Castor oil, 178, 272 Catalytic action, 138, 155, 255, 263 Catalysis, 155 Catechol, 310 Cathode, 58 Cations, 58 Celloidin, 262 Celluloid, 262 CeUulose, 261 Cellulose nitrates, 262 Centric benzene formula, 288 Cephalin, 191 Ceryl alcohol, 166 Cetyl alcohol, 166 Cetyl palmitate, 166 Chemical equilibrium, 151 Chemical structure, how deter- mined, 6 Chinoline, 378 Chiaosol, 378 Chloracetic acids, 146 Chloral, 130 Chloral alcoholate, 130 Chloralamide, 132 Chloral formamide, 132 Chloral hydrate, 130 Chloralose, 132 Chloral substitutes, 131 Chloranil, 332 Chlorbenzene, 298, 335 Chlorbenzoic acids, 299, 322 Chlorbenzyl alcohol, 315 Chloretone, 165 Chlorhydrins, 174 Chloroform, 104 " , acetone,. 165 " , as reducing agent, 253 " , molecular weight determina- tion, 39 Chlorpropionic acids, 160 Chlortoluenes, 299 Cholahc acid, 204 Cholesterine, 280 Cholesterol, 280 Cholic acid, 204 Choline, 190 Chromophore group, 365 Chrysarobin, 372 Chrysophanic acid, 372 Cinchonidine, 383, 391 Cinchonine, 378, 383, 390 Cinnamic acid, 366 Cinnamic aldehyde, 366 Cinnamon oil, 366 Citrates, 210 Citric acid, 210 Closed carbon chains, 276 Cloves, oil of, 366 Coal gas, 96 Cocaine, 383, 389 Codeine, 383, 396 Cod liver oU, 178 416 INDEX. Colchicine, 383, 399 Collargol, 69 Collie's benzene model, 288 Collodion, 262 Colloidal solutions, 61, 263, 369 Colloids, 61, 263 " , irreversible, 66 " , reversible, 67 Combustion analysis, 25 ' ' analysis, modified when halogens present, 34 ' ' analysis, modified when nitrogen present, 31 ' ' analysis, modified when sulphur present, 34 " furnace, 26 Condensation, 247, 249 Condensed benzene rings, 368 Conductivity, electrical, 57 Conglomerates, 200 Congo red, 361, 369 Coniine, 382, 385 Constants, 52 Constitutional formula, see ■ I Structural. Copper acetate, 142 Copper acetylide, 274 ' Copper-zinc couple, 95 Cordite, 175 Corn starch, 118 Cotarnine, 395 Cream of tartar, 207 Creatin, 230 Creatinin, 230 Creolin, 308 Creosote, 308 Creosote oil, 283 Creosotol, 308 Cresols, 308 Croton chloral, 132 Crotonic acid, 271 Croton oil, 178 Crystallization, 7 Cryoscopy, 51 Crystals, purity of, 9 Curarine, 283 Cyanacetic acid, 232 Cyan acids, 186 Cyanamide, 223 Cyanic acid, 186, 223 Cyanides, 91, 184 " , aromatic, 341 Cyanogen compounds, 80 Cyanpropionic acids, 171 Cyclic compounds, 275 Cyclopentane, 275 Cyclopropane, 275 Cycloses, 276 Cymene, 276, 297 Cymogene, 98 Cystein, 217 Cystin, 217 Cytosin, 239 Dalton's law, 36 Definition of organic chemis- try, 1 Denatured alcohol, 118 Depression of freezing-point by solutions, 51 Dermatol, 352 Destructive distillation, 139 Developers, photographic, 310 Dextrin, 117, 263, 264 Dextroconiine, 386 Dextrolactic acid, 201 Dextrose, 246, 253 Diabetes, 253 Diacid phenols, 310 Dialkyl sulphides, 194 Dialuric acid, 234 Dialysis, 19 Diamine - dihydroxy-diarseno (di) benzene, 344 Dianthracene, 370 Diastase, 116 Diazoaminobenzene, 337 Diazoamino compounds, 337 Diazo compounds, 334 INDEX. 417 Diazonium salts, 334 Diazotizing, 303 Dibasic aromatic acids, 324 Dibrommethane, 104 Dichloracetic acid, 146 Dichlorhydrin, 174 Dichlormethane, 104 Diethyl oxalate, 221 Digitalin, 266 Digitalose, 246 Digitonin, 267 Digitoxin, 266 Digitoxose, 245 Diglyeeride, 180 Dihydroxyacetone, 244 Dihydroxyanthraquinone, 371 Dihydroxybenzoic acid, 350 Dihydroxydibasic acids, 205 Dihydroxymonobasic acids, 203 Dihydroxjrphenylacetic acid, 353 Dihydroxytoluene, 311 Dihydroxy stearic acid, 177, 180 Diiodoform, 108 Diiodomethane, 104 Diiodomethyl salicylate, 349 Diketones, 364 Dimethylamine, 189 Dimethylaminoazobenzene, 337, 361 Dimethylaminoazobenzene-sul- phonic acid, 357 Dimethylaniline, 332 Dimethyl strychnine, 392 Dimethyl xanthin, 237 Dinitrobenzene, 290, 328 Dionine, 397 Dioses, 244 Dioxyindol, 376 Dipalmito-olein, 177 " -stearin, 177 Dipeptides, 240 Diphenylamine, 332 Diphenylaminoazobenzene-sul- phonic acid, 358 Diphenylketone, 363 Disaccharides, 244, 255 Dissociation, coefficient of, 59 Dissociation constants of acids, 409 of bases, 409 " , electrolj^ic, 57 Distillation, destructive, 139 " , fractional, 13 " , steam, 15 " , vacuimi, 15 Disuccinyl peroxide, 172 Dithymol diiodide, 309 Dormiol, 132 Drug principles, 382, 399 Dulcitol, 248 Dumas, vapoiu- density deter- mination, 38 Ductal, 310 Durene, 296 Dyes, 365 Dynamic bonds, 288 Djmamite, 175 Ecgonine, 389 Egg membrane, osmotic pres- sure, 50 Eka-iodoform, 108 Elaterin, 370 Electrical conductivity of solu- tions, 57 Electrolytes, 57 Electrolytic dissociation, 57 Elements in organic compounds, 2 Emetine, 383 Emodin, 372 Empirical formula, 5, 76 Emulsin, 260, 266, 315 Emulsions, 62 Emulsoids, 62 Enzymes, 117 Enzymes, adsorption of, 72 " , as colloids, 69 Eosin, 326 Epicarin, 369 Epinephrin, 354 418 INDEX. Equilibrium of ions and mole- cules, 60 Ergotinine, 384 Ergotoxine, 384 Erucic acid, 272 Erythrodextrine, 264 Eseridine, 383 Eserine, 383 Esterification, 151 Esters, 149 ' Ester value, 179 Ethanal, 127 Ethane, 82, 97 Ethene, 269 Ethereal salts, 142, 154 Ethers, 86, 109 ' ' , aromatic fatty, 305 " , mixed, 111 ' ' , true aromatic, 305 Ether value, 179 Ethyl acetate, 155 " alcohol, 115 " amine, 188 " benzene, 295 " benzoate, 320 " bromide, 102 " butyrate, 161 " carbamate, 212 " carbonate, 223 " chloride, 102 " cyanide, 184 " ether, 109 " glycollate, 197 ' ' gly collie acid, 197 ' ' nitrite, 193 ' ' sulphonic acid, 194 " sulphuric acid, 110 Ethylene, 167, 269 " bromide, 167 " " , preparation of, 269 ' ' lactic acid, 198 Ethylenes, 269 Eucaine, a and p, 386 EucaljTjtus oil, 297 Eudoxine, 325 Eugenol, 366 " acetamide, 366 carbinol, 366 iodide, 366 Eumydrine, 388 Euquinine, 391 Euthalmin, 386 Exalgin, 334 Fats, 176 ' ' , vegetable, 178 Fatty acids, 133 " " , volatile, 177 " compounds, synopsis of, 93 Fat values, 178 Fehling's solution, 255 Fermentation, 252, 255 Filicic acid, 313 Fire damp, 95 Fischer, Emil, 242 Flashing point of oils, 99 Fluorescein, 311, 325 Formaldehyde, 124 Formaline, 124 Formamide, 219 Formic acid, 134 " series, 134, 162 Formonitrile, 185 Formula, calculation from per- centage composition, 34 Formulae, empirical and struc- tural, 76 Fractional crystallization, 9, 170, 201 Fractional distillation, 13 Fractionating flask, 13 Freezing-point constants, 52 ' ' depression by so- lutions, 51 Fructose, 253 Fruit sugar, 253 Fuchsin, 331 Fuchsin aldehyde reaction, 124, Fusel oil, 120 INDEX. 419 Galactose, 246, 253 " test, 260 Galactosamine, 249 Gallic acid, 312, 350 Gallisin, 259 GaU-nuts, 350 Garlic, oil, of, 272 Gas, coal, 96 ' ' laws, 36 " , natural, 96 Gases, molecular weight of, 37 Gasoline, 98 Gasoline, fuel value, 99 Gastric juice, 159, 361 Gaultherin, 266 Gay-Lussac's law, 36 Gelatine dynamite, 175 Gelose, 265 Gelseminine, 383 Glucoproteins, 248 Glucosamine, 249 Glucosazone, 250 Glucose, 253 d-Glucose, a and p, 252 Glucosides, 265 Glucosides, artificial, 267 Gluoosone, 251 Glutamic acid, 214 Glutamin, 222 Glutaminic acid, 214 Glutaric acid, 169 Glutol, 125 Glyceric acid, 175, 203, 249 " aldehyde, 244 Glycerine, 173 Glycerol, 173, 244, 271 Glycerophosphoric acid, 176 Glycerose, 244 Glyceryl acetates, 179 " butyrate, 174 " tribenzoate, 321 " trioleate, 176 " tripahnitate, 176 " tristearate, 176 Glycin, 213 Glycinamide, 193, 221, 226, 241 Glycocoll, 197, 204, 213, 322 GlycochoUc acid, 204 Glycogen, 66, 264 Glycol, 167 " aldehyde, 244 Glycolates, 168 GlycoUates, 197 Glycollic acetate, 197 " acid, 168, 196 " aldehyde, 168 Glycollid, 198 Glycuronates, paired, 205 Glycuronic acid, 204, 248, 253 Glyoxal, 168 Glyoxyhc acid, 168, 203 Gram molecular solution, 44 Gram molecule, 3^ Grape sugar, 253 Green soap, 181 Guaiacol, 308, 310 ' ' benzoate, 310 Guanidin, 229 Guanin, 238 Gum Arabic, 265 " benzoin, 320 Gums, 265 Gum tragacanth, 265 Guncotton, 262 Gtinzberg's reagent, 312, 361 Gutta percha, 280 Haematin, 374 Haematoporphyrin, 374 Haemin, 374 HaUdes, 86 Halogens, detection of, 4 Halogen derivatives of paraf- fins, 101 " " benzenes, 298 Headache medicines, 333 Heat of combustion, 97, 113 Heavy oil, 283 Hedonal, 228 Helianthin, 357 Heptoses, 244, 255 420 INDEX. Heroine, 397 Heterocyclic compounds, 93, 373 Hexabasic acid, 326 Hexachlorbenzene, 298 Hexamethylentetramine, 192 Hexane, 82, 100 Hexone bases, 216 Hexoses, 246 Hippuric acid, 322 Holooain, 344 Homatropine, 383, 389 Homogentisic acid, 353 Homologous series, 82 Homologues of benzene, 294 Hydrastine, 383, 394 Hydrastinine, 382, 394 Hydrazine, 338 Hydrazobenzene, 337 Hydrazones, 124, 250, 316 Hydrion, 148 Hydrocarbons, 80 " , , aromatic, 281 " , cyclic, 275 ' ' , groups of, 80 " , saturated, 81, 94 " , unsaturated, 81, 268 Hydrocinnamic acid, 324 Hydrocyanic acid, 185 Hydrogels, 68 Hydrogen, detection of, 3 " , estimation of, 25 " , nascent, 95 Hydrolysis, 133 " , power of acids to cause, 410 Hydrometer, 21 Hydroquinol, 311 Hydroquinone, 311 Hydrosols, 68 Hydroxion, 149 Hydroxyacetic acid, 196 Hydroxy acids, 92, 196 Hydroxybenzoic acids, 345 p-Hydroxybutyric acid, 202 Hydroxycamphor, 279 Hydroxy compounds, aromatic, 343 Hydroxycymenes, 309 p-Hydroxyethyl-sulphonic acid, 202 Hydroxyformic acid, 196 Hydroxyhydroquinol, 313 Hydroxyl group, nature of, li2 Hydroxyl, test for, 112, 122 Hydroxyprolin, 216, 373 Hydroxjfpropionic acids,' 198 Hydroxytoluenes, 308 Hyoscine, 383, 389 Hyoscyamine, 383, 388 Hypertonic solutions, 48 Hypnal, 132 Hypnone, 364 Hypotonic solutions, 48 Hypoxanthin, 237 Ichthyol, 195 Identification of substances, 19, 23 Illuminating gas, 96 Imido compounds, 229 Imido group, 91 Indican, 375 Indicators, 358 Indigo, 330, 376 Indigo red, 377 ' ' , synthesis of, 376 ' ' , white, 377 Indirubin, 377 Indol, 375 Indolaminopropionic acid, 376 Indoxylglycuronic acid, 375 Indoxylsulphuric acid, 375 Ink, 352 Inosite, 276 Inversion, 256 Invertases, 255 Invert sugar, 255, 260 lodal, 107 Iodine, dextrine test, 264 " , glycogen test, 265 ' ' , starch test, 263 INDEX. 421 Iodine value, 179 lodobenzene, 298 Iodoform, 108 lodoformin, 108 lodoformogen, 108 lodol, 373 lodothyrin, 242 Ionization, 57 " constants, 149, 409 " experiment, 307 ' ' of indicators, 368 Ions, 57 ' ' , electrical charge of, 58 Isatin, 376 Isethionic acid, 202 Isoamyl alcohol, primary, 120 " " , tertiary, 121 " acetate, 155 Iso-butane, 99 Isobutyl alcohol, 120 " carbinol, 120 Isobutyric acid, 160 Isocholesterol, 280 Iso-compomids, 84, 99 Isocyanide reaction, 186 Isocyanides, 185 IsocycUc compounds, 93 Isoleucin, 214 Isomaltose, 252, 259 Isomerism, 76, 84 ' ' , stereo-chemical, 198 Isomers, 76 Isonitriles, 185 Isoosmotic solutions, 48 Iso-paraffins, 99 Iso-pentane, 100 Isopropylmetacresol, 309 Isopropylorthocresol, 309 IsoquinoUne, 380 Isosuccinic acid, 172 Isotonic coefficient, 49 " solutions, 48 Isovaleric acid, 161 Jervine, 383 Kairine, 379 Kekule, 287 Kerosene, 98 Ketohexose, 247 Ketone acid, 202 Ketones, 91, 163 ' ' , aromatic, 363 " , mixed aromatic fatty, 363 Ketose, 244, 246 ' ' test, 254 Kjeldahl's method of nitrogen estimation, 34 Koprosterol, 280 Kynurenic acid, 379 Lacmoid, 311 Lactates, 201 Lactic acid, 115, 198, 249, 259 Lactid, 202 Lactocaramel, 259 Lactones, 203 Lactophenin, 344 Lactosazone, 254 Lactose, 255, 257, 259 Lactylphenetidin, 344 Laevolactic acid, 200 Lsevulose, 246, 250, 253 Lanolin, 166, 183 Lard, 177 Laurie acid, 162 Lead acetate, 142 " , basic, 142 " , sugar of, 142 Lecithin, 190 Leucin, 214 Leucomaines, 240 Light oil, 283 Lignin test, 261 Ligroin, 98 Linoleic acid, 272 Litmus, 362 Lobeline, 383 Lowering of freezing-point, 51 Lubricating oil, 99 Lycetol, 192 422 INDEX. Lysidin, 192 Lysin, 215 Lysol, 308 Malic acid, 205 Malonic acid, 169 Malt, 116 " liquors, 116 Maltodextrin, 264 Maltosazone, 254 Maltose, 117, 252, 255, 257, 259 Mandelic acid, 324 Mannose, 247 Maple sugar, 258 Marsh gas, see Methane. Marsh gas series, 94 Mass action, 151 Measuring osmotic pressure, 44 Melissic alcohol, 166 Mellite, 326 Mellitic acid, 326 Melting-point determination, 9 Menthol, 279 Meroaptans, 91, 194 Mesitylene, 295 " , preparation of, 296 Mesitylenio acid, 295, 324 Mesotartario acid, 207 Mcsoxalic acid, 205 Meta compounds, 291 Metadihydroxybenzene, 311 Metaldehyde, 127 Metaaulphobenzoic acid, 355 Metaxylene, 324 Methanal, 124 Methane, 82, 94, 95 Methane series, 94 Methanoic acid, .134 Methoxyhydrastine, 394 Methyl, 86 Methyl acetanilide, 334 Methyl acetate, 155 Methyl alcohol, 114 Methylamine, 189 Methylaniline, 332 Methylated alcohol, 118 Methyl carbinol, 115 Methyl chloride, 102 ' ' cro tonic acid, 271 " cyanide, 184 " ether, 109 " ethyl ether. Ill " glycocoU, 213 " guanidin, 230 guanin,'238 " hexoses, 247 " indol, 376 " isocyanide, 185 " orange, 357 Methylene blue, 332 Methyl pentoses, 245 Methylphenylhydrazine, 250 Methylphenyl ketone, 364 Methyl pyridines, 374 " saUcylate, 347 " strychnine, 392 ' ' thionin hydrochloride, 332 " violet, 332 ' ' xanthins, 238 Meyer, Victor, method, 39 Milk sugar, 269 Mixed aromatic compoimds, 343 Mixed compounds, 196, 343 Mixed compounds, paraffin de- rivatives, 92, 196 Models representing formulse, 84 Models to represent stereoiso- merism, 206 Mol, 37 Molasses, 258 Molecular disperse solutions, 62 Molecular weight: Calculated from freezing- point determination, 55 Calculated from osmotic pres- sure, 45 Calculated from vapour den- sity determination, 41 Determined by analysis of derivatives, 75 INDEX. 423 Molecular weight: Determined by depression of freezing-point, 51 Molecular weight of gases and vapours, 37 Molecular weight of colloids, 64 Molisch's test, 250, 267 Monobasic acids, 75 Monobromethane, 102 Monobromisovaleryl-urea, 228 Monochloracetic acid, 146 Monochlorethane, 102 Monochlorhydrin, 174 Monochlormethane, 96 Monoformin, 137 Monohydroxybenzene, 301 Monohydroxybenzoic acids, 345 Monohydroxydibasic acids, 205 Monohydroxytribaaic acids, 210 Monomethyldihydroxyanthrar quinone, 372 Monomethyltrihydroxyanthra- quinone, 372 Mononitrobenzene, 327 Mononitrophenol, 306 Monosaccharides, 243 " , general reac- tions of, 250 Monose, 243 Mordants, 366 Morphine, 383, 395 Mucic acid, 248 Multirotation, 251 Muscarine; 191 Mustard oil, 273, 308 Mycoderma aceti, 138 Myristic acid, 162 Naphtha, 98 Naphthalene, 368 Naphthols, 368 P-Naphthol benzoate, 369 a-Naphthol-orthohydroxytoluic acid, 369 Naphthylamines, 369 Naphthylamine-sulphonic acid, 369 Narceine, 383, 395 Narcotine, 383, 394 Nascent hydrogen, 95 Natural gas, 96 Neo-pentane, 100 Neurine, 192 Nicotine, 382, 385 Nirvanin, 349 Nitriles, acid, 185 Nitrites, 193 Nitrobenzene, 327 Nitrobenzoic acids, 322, 355 Nitrocellulose, 262 Nitro-compounds, 193 " , aromatic, 327 Nitroparaffins, 193 Nitrogen derivatives of paraf- fins, 91, 184 ' ' , detection of, 3 ' ' , estimation by combus- tion, 32 " , estimation by Kjel- dahl's method, 34 tables, 405 Nitroglycerine, 175 Nitroglycerol, 175 Nitrophenols, 343 Nitrous acid, action on amines, 189 Non-electrolytes, 57 Nonoses, 244, 255 Normal compounds, 84 Nosophen, 325 Novaine, 190 Novaspirin, 350 Novocaine, 322 Nucleic acid, 239 Nuclein bodies, 238 Nucleoproteins, 249 Octoses, 244,, 255 Oil of bitter almonds, 315 " " caraway, 309 " " cinnamon, 366 424 INDEX. Oil of cloves, 366 " " eucalyptus, 297 " " garlic, 272 " " peppermint, 279 " " sassafras, 366 " " thyme, 297 " " turpentine, 277 " " wintergreen, 247 Olefiant gas, 269 Olefins, 269 Oleic acid, 271 Olein, 176 Oleomargarine, 160 Oleo-paJmito-stearin, 177 Olive oil, 178 Opium alkaloids, 393, 395 Optical activity, 200 Optical activity of protein de- composition products, 216 Orange II, 357 Orangine powders, 333 Orcein, 311 Orcin, 311 Orcinol, 311 Organic chemistry, definition of, 1 Organic chemistry, preliminary survey of, 79 Organic compounds, synopsis of, 92 Organic substances, solvents of, 7 Ornithin, 215 Orphol, 369 Ortho compounds, 291 Orthodihydroxybenzene, 310 Orthoform, 349 Orthophthahc acid, 324 Osazones, 250, 254, 259 ' ' , melting-points of, 254 Osmose, 63 Osmotic cell, 43 Osmotic pressure, 41 Osmotic pressure of hsemoglobin, 64 Osmotic pressure of gelatine, 64 Osmotic pressure, determination of, with red blood cells, 48 Osmotic pressure, effect of tem- perature on, 45 Osmotic pressure, effect of con- centration of solution on, 46 Osone, 251 Oxalates, 170 Oxalic acid, 169 Oxaluric acid, 232 Oxamide, 221 Oxycamphor, 279 Oxygen, calculation of percent- age of, 31 Oxyproteic acid, 242 Oxyquinoline sulphate, 378 Palladium-hydrogen experiment, 42 Palmitic acid, 162, 272 Palmitin, 176 Palmito-distearin, 177 Papaverine, 383, 393 Paper, 261 Parabanic acid, 232 Para compounds, 291 Paradihydroxybenzenc, 311 Paraffin, 99 " derivatives, 85 oil, 98 " series, 94 Paraffins, 81, 94 " , boiling-points, spe- cific gravities, etc., 97 " , heat of combustion of, 97 ' ' , synthesis of, 94 Paraform, 125 Paraformaldehyde, 124 Parahydroxymetamethoxyallyl- benzene, 366 Parahydroxytolyl mustard oil, 308 Paraldehyde, 127 Paraminophenol, 334 INDEX. 425 Paraminosulphonic acid, 356 Paraphenetidin, 344 Paratoluic acid, 276, 323 Parchment paper, 261 Pelletierine, 382 Pentane, 82, 100 Pentoses, 245 Pentose test, 246 Peppermint, oil of, 280 Peptides, 240 Peptone, 241 Percentage composition, calcu- lated from analysis, 31 Peronine, 397 Petroleum, 98 ether, 98 " ether, specific grav- ity of, 22 Phenacetin, 344 Phenanthrene, 372 Phenazone, 339 Phendiol, 310 Phenetole, 305, 335 Phenocoll, 344 Phenol, 301, 302, 335, 341 Phenol, derivatives of, 305 ' ' , substitution products of, 306 Phenolates, 301 Phenolphthalein, 324, 326, 358 361 " tautomerism of, 360 Phenol-sulphonic acids, 307, 343 Phenols, 301 " , diacid, 302, 310 " , monacid, 302 " , triacid, 302, 312 Phenoxides, 301 Phentriol, 312 Phenyl, 294 Phenylacetamide, 333 Phenyl acetate, 305 ' ' acetic acid, 324 " alanin, 214, 353 " amine, 329 Phenyl carbinol, 314 Phenyldimethylpyrazolone, 339 Phenylethyl ether, 305 Phenylhydrazine, 124, 250, 316, 338 Phenylmethyl ether, 305 Phenylpropionic acid, 324 Phenyl salicylate, 347 Phenyltolylketone, 363 Phloretin, 266 Phloridzin, 266 Phloroglucin, 312 Phloroglucinol, 312 Phloroglucin-vaniUin reagent, 312, 361 Phosgene, 105 Phosphatides, 191 Phosphine, substitution deriva- tives of, 192 Phosphorus-containing com- pounds, 191 ' ' , detection of, 4 PhthaKc acid, 294, 311, 324 ' ' anhydride, 324 PhthaUmide, 326 Physical properties of sub- stances, 20 Physostigmine, 383 Phytosterol, 280 Picnometer, 20 Picric acid, 306, 365 PicropodophyUin, 399 Picrotoxin, 399 Pilocarpidine, 382 Pilocarpine, 399 Pinene, 276 ' ' hydrochloride, 277 Pine oils, 277 Pintsch gas, 96 Piperazine, 192 Piperidine, 385 Piperine, 383, 385 Plasmolysis, 50 Polarization, 259 PoljTnerization, 124, 127 Polj'mers, 124 426 INDEX. Polyose, 243 Polypeptides, 240 Polysaccharides, 244 Polyterpenes, 279 Potassium acetate, 142 " acid tartrate, 208 ' ' antimonyl tartrate, 209 ' ' benzene sulphonate, 302, 319, 341 ' ' hydroxide, specific gravity table, 407 ' ' phenol sulphate, 305 Pressure, osmotic, 41 " , vapour, 408 Primary alcohols, 87, 112 " amines, 186 Prolin, 216, 373 Propane, 82, 97 Propane, 271 Propenol, 271 Propionic acid, 159 Propyl alcohol, 119 " " , secondary, 163 Propylene, 174 a-Propyl piperidine, 385 Protamines, 216 Protein, formation of dextrose from, 249 ' ' , synthesis of, 240 Proteins, classes of, 242 Protocatechuic acid, 354 Prussic acid, see Hydrocyanic acid. Pseudo-catalyst, 155 Ptomaines, 191 Purification of substances, 7 Purin bodies, 236 ' ' nucleus, 236 Putrescine, 192 Pyoktanin, 332 Pyrazole, 373 Pyridine, 374 bases, 283, 374 Pyrimidin derivatives, 239 Pyrimidin ring, 232 Pyrocatechin, 310 Pyrocatechol, 310 Pyrogallic acid, 312 Pyrogallol, 312 Pyroligneous acid, 139 Pyroxylin, 262 Pyrrol, 373 Pyrrolidine, 373 a-Pyrrolidine-carboxylic acid, 216 Pyrrolidine derivatives, 387 Quantitative analysis, 25, 75 Quaternary bases, 91, 189 Quinalgen, 379 Quinidine, 391 Quinine, 378, 383, 391 " bisulphate, 363 Quinine-urea hydrochloride, 391 Quinoid structure, 361 Quinol, 311 Quinoline, 278 Quinones, 364 Racemic lactic acid, 200 " substances, 200 " tartaric acid, 207 Reduction tests, 250 Reference books, 401 Reichert-Meiasl value, 178, 180 Resorcin, 311 Resorcinol, 311 Reversible reactions, 151 Rhamnose, 246 Rhein, 372 Rhigoline, 98 Ricinoleic acid, 272 Rochelle salts, 208 Rosaniline, 331 Rotation of polarized light, 200 Rotatory power of sugars, 251, 260 Rubber, 280 INDEX. 427 Saccharates, 258 Saccharic acid, 248 Saccharin, 355 Saccharose, 256, 268 Safrol, 366 Sajodin, 162 Sahcin, 266, 345 SalicyUc acid, 347 " " combustion anal- ysis of, 29 SaUcyl-sulphonic acid, 348 Sahgenin, 266, 345 Salipyrin, 349 Salol, 345 Salophen, 349 Salting out, 303 Sandalwood oil, 279 Sanguinarine, 383 Sanoform, 349 Santonin, 369 Santoninic acid, 369 Saponification, 155, 181 ' ' value, 179 Saponin, 267 Sarcolactic acid, 201 Sarcosin, 213 Sassafras oil, 366 Saturated hydrocarbons, 81, 94 Schiff's reagent, 130 Schweitzer's reagent, 261 Scopolamine, 383, 389 Scopolin, 389 Secondary alcohols, 87, 163 " amines, 186 Selective permeabihty, 50 Semipermeable membrane, 44 Serin, 213, 249 Side chain, 84, 318 Sidonal, 192 Silk, artificial, 262 Sinalbin, 267, 308 Sinigrin, 267 Sinipine, 383' " Six hundred and six," 344 Skatol, 375 Skatoxylsulphuric acid, 376 Smokeless powder, 262 Soap, castile, 182 " , cleansing action of, 182 " , green, 181 ' ' , hard, 181 " , resin, 182 ' ' , soft, 181 ' ' , Venetian, 182 Soaps, 181 Sodium acetate, 142 " amalgam, 204 ' ' hydroxide, specific grav- ity table, 406 " ' methyl, 108 " methylate, 113 " phenylcarbonate, 346 ' ' potassium tartrate, 208 " salicylate, 346 Solute, 43 Solutions, 51 , coUoidal, 61 " , electrical conductiv- ity of, 57 ' ' , isotonic, hypotonic, hypertonic, 48 ' ' , obedience to gas laws, 45 Solvents, 7 Sorbitol, 248 Sparteine, 382, 384, 386 Spatial representation of mole-. cules, 198 Specific gravity determination, 20 " ofUquids, 20 " " of solids, 21 " " tables, 403, 405-408 Spermine, 192 Starch, 65, 263 " , soluble, 65 Steam distillation, 15 Stearic acid, 162, 272 Stearin, 176 Stereochemical isomerism, 198 Stereoisomerism, 198 428 INDEX. Sterins, 280 Stovaine, 322 Strophanthin, 266 Structural formula, 76 Structural formula of acetic acid, proof of, 140 Strychnine, 388, 391 Stypticin, 395 Sublimation, 12 Substituted ammonias: Primary, 186 Secondary, 186 Tertiary, 186 Succinic acid, 171 Succinic anhydride, 171 Succinimide, 229 Sucrose, 256, 258 Sugars, comparative reducing power of, 256 " , estimation of, 256 " , specific rotation of, 260 " , tests of, 253,254 Sulphanilic acid, 356 Sulphobenzoic acids, 322 Sulphocyanic acid, 186 Sulphonal, 194 Sulphones, 194 Sulphonic acids, 92, 194 " " , aromatic, 340 " chlorides, 340 Sulphonmethane, 194 Sulphur alcohols, 91, 194 ' ' -containing amido acids, 217 " derivatives of paraf- fins, 91, 194 ' ' , detection of, 3 ethers, 91, 194 Suprarenin, 354 Surface tension, 69 Suspensoids, 61 Synthesis, 5 Tannacol, 352 Tannalbin, 352 Tannic acid, 68, 351 Tannigen, 352 Tannin, 351 Tannins, 352 Tannoform, 352 Tannopin, 352 Tartar emetic, 209 Tartaric acids, 206 Tartronic acid, 176, 205, 234 Taurin, 217 Taurocholic acid, 204 Tautomerism, 235, 311, 360 Terpenes, 276 Terpin hydrate, 277 Tertiary alcohols, 88, 166 " amines, 186 bases, 91, 382 Tetrachlormethane, 97, 104 Tetraethylammonium hydrox- ide, 189 Tetra-iodo-methane, 108 Tetra-iodo-pyrrol, 373 Tetramethoxybenzylisoquino- Une, 393 Tetranitrol, 175 Tetraphenylhydrazine, 333 Tetronal, 195 Tetrose, 244 Thalline, 379 Thebaine, 383, 397 Theobromine, 237, 382, 399 Theophylline, 382, 399 Thio alcohols, 194 Thiophene, 283, 373 Thiophenol, 340 Thiosinamine, 273 Thyme, oil of, 297, 309 Thymin, 239 Thymol, 308 Tiglic acid, 271 ToUiene, 294 Toluene-sulphonio acids, 340, 342 . Toluic acids, 294 Toluidines, 331 Toluol, 294 INDEX. 429 Tolyl carbinol, 315 Tragacanth, gum, 265 Traube's synthesis, 232 Tribrommethane, 104 Tribromphenol, 304, 306 Trichloracetic acid, 146 Trichloraldehyde, 130 Trichlorhydrin, 174 Trichlorlactamide, 234 Trichlormethane, 96, 104 Trichlortertiary butyl alcohol, 165 Trihydroxybenzene, 312 Trihydroxybenzoic acid, 350 Triiodoacetone, 165 Triiodomethano, 104 Trimethylamine, 189 Trinitrobenzene, 290 TrinitroceUulose, 262 Trinitophenol, 306 Trional, 195 Trioses, 244 Triphenylamine, 332 Trisaccharides, 243, 260 Tropacocaine, 390 TropsBolin 00, 358 Tropic acid, 388 Tropine, 387 Tryptophan, 204, 216, 376 Turpentine, 277 Tussol, 339 Tyrosin, 214, 353 Ultramicroscope, 64 Unsaturated hydrocarbons, 92 Uracil, 239 Urates, 235 Urea, 222 " , freezing-point determina- tion of molecular weight, 55 " , nitrate, 226 " oxalate, 226 ' ' , specific gravity of, 22 " , synthesis of, 2, 211, 226 Urea, tests, 227 Urethane, 212 Uric acid, 231, 237 " , tautomerism of, 235 Urine, depression of freezing- point of, 56 Urinometer, 21 Urotropine, 192 / Vacuum dis'tiUation, 15 Valence of elements in organic compounds, 2 Valerianic acid, 161 Valeric acid, 161 VaUn, 214 Vanilla, 350 Vanillic acid, 350 VaniUin, 312, 350 Vapours, molecular weight of, 38 Vapour tension table, 408 Vaseline, 99 Vegetable bases, see Alkaloids. Veratrine, 384 Veronal, 228 Victor Meyer's vapour density method, 39 Vinegar, 138 Viscosity, 73 " of colloidal solutions, 67,74 Von Baeyer's reagent, 270 Water-gas, 96 Waxes, 166 Weight normal solutions, 44 \ Westphal's balance, 21 Whiskey, 116 Wines, 116 Wintergreen, oil of, 347 Wood alcohol, 114 " turpentme, 277 Xanthin, 237 bodies, 238 430 INDEX. Xylene, meta, 294, 296 Xylenes, 294 Xylidines, 331 Xylol, 294 Xylose, 245 Yeast, fermentation by, 117 Yohimbine, 383 Zinc methyl, 108 Zymase, 117 SHORT-TITLE CATALOGUE OF THE PUBLICATIONS OF JOHN WILEY & SONS NEW YORK London: CHAPMAN & HALL, Limited Montreal, Can.: RENOUF PUB. CO. ' ARRANGED UNDER SUBJECTS Descriptive circulars sent on application. Books marked with an asterisk-f*;). are sold at we/ prices only. All books are bound in cloth unless otherwise stated.. ..a AGRICULTURE— HORTICULTURE— FORESTRY. 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