acetanilide produces symptoms of coma and collapse, and the best antidote is copious drafts of brandy. Dose.-250 milligrammes (4 grains). ACETANILIDE DERIVATIVES AND SUBSTITUTES Bromacetanilide is formed when one of the hydrogen atoms of the benzene nucleus is replaced by bromine. It is an antipyretic and antiseptic. Dose, 1 to 8 grains. Benzanilide.-In this the benzoyl (C,H,CO) group is substituted for the acetyl group in the acetanilide. Exalgin is methyl acetanilide, or, more properly speaking, acettoluidide, and is made by heating toluidin (C,H,H) with glacial acetic acid. Antikamnia is a mixture of acetanilide, caffeine, tartaric acid, and sodium bicarbonate. A combination of this character is recognized in the pharmacopoeia as Compound Powder of Acetanilide (p. 301). Antinervine is a compound consisting of 50 per cent. acetanilide, 25 per cent. each ammonium bromide and salicylic acid. A phenol derivative [Acetparaphenetidin, C.H ̧(OCH ̧).NH.CH,.CO 1:4], the product of acetylization of para-amidophenetol. White, glistening, crystalline scales or fine crystalline powder, odorless and taste less. It is soluble in 925 parts of water, 12 parts of alcohol, 63 parts of ether, and 20 parts of chloroform at 25° C. (77° F.); in 70 parts of boiling water and in 2 parts of boiling alcohol. Heated to between 134° and 135° C. (273.2° and 275° F.) it melts, and at a higher temperature burns without leaving a weighable residue. It dissolves without color in sulphuric acid, but if shaken with nitric acid it is colored yellow, which color persists when heated. If 0.1 Gm. of Acetphenetidin be boiled for one minute with 1 Cc. of concentrated hydrochloric acid and the solution diluted with 10 Cc. of water, cooled and filtered, it should yield on addition of 3 drops of an aqueous solution of chromium trioxide (1 in 30) a ruby red color. On heating 0.1 Gm. of Acetphenetidin with 5 Cc. of a concentrated solution of potassium hydroxide (1 in 4), the odor of aniline should not be perceptible. If 0.1 Gm. of Acetphenetidin be boiled with 10 Cc. of water it should yield a solution which, when cooled and filtered, should not become turbid upon the addition of bromine T.S. in slight excess (absence of acetanilide). If 0.1 Gm. of Acetphenetidin be boiled for one minute with 3 Cc. of solution of sodium hydroxide (1 in 2), the solution cooled, and then agitated with 5 Cc. of a solution of chlorinated soda, there should be produced a clear yellow liquid, and not a purplish-red or brownish-red cloudy liquid or precipitate (absence of acetanilide). A mixture of 0.3 Gm. of Acetphenetidin with 1 Cc. of 90 per cent. alcohol should not acquire a red tint when diluted with three times its volume of water and boiled with one drop of tenth-normal iodine V.S. (absence of paraphenetidin). Tests for Identity.-Given above. LOC2H 3 Remarks. This body, commonly known as phenacetine, has the formula C.H<NHC,H,O. It represents acetanilide in which one of the hydrogen atoms is replaced by an OC,H, group. Speaking more technically, it represents an ethyl acetyl derivative of para-amidophenol, CH,NH, and is made by the reduction of para-nitrophenol, which, in turn, is prepared by treating carbolic acid with cold diluted nitric acid. By treating para-amido-phenol with ethyl iodide, OH LOC2H p-phenetidin, C.H.<NH, is produced, and by treating the latter with glacial acetic acid acetyl phenetidin or phenacetine results. Phenacetine is a white powder that melts at 134° to 135° C. It is one of the most valuable antipyretics. Phenacetine is sometimes contaminated with phenetidin. This latter is a dangerous irritant, hence such adulterated phenacetine should not be dispensed. Detection of same is easily accomplished by the pharmacopoeial test given above. Some unscrupulous dealers have adulterated phenacetine with acetanilide, but this can be easily detected by means of the meltingpoint-phenacetine, 134° to 135°; acetanilide, 113°-or by two pharmacopoeial chemical tests given above. Dose.-500 milligrammes (7 grains). As with all the successful modern synthetics, the introduction of phenacetine was followed by a large number of bodies of similar composition. Thus we have iodophenin, which represents phenacetine hydrochloride combined with iodine and potassium iodide. OCH, differs from phenacetine only in having a methyl group instead of the ethyl group of phenacetine, and, like it, is used as an antipyretic. Methacetin, CH,NHCH,O' Hydracetin or pyrodin, CH-NH NHC,H,O which is acetphenylhydrazin and made similar to acetanilide, save for the use of phenylhydrazin instead of aniline. Phenocoll hydrochloride, CH,CH,NH,+HC, is made by treating phenet NH idin with amido-acetic acid, CH, COOH (glycocoll). Phenacoll hydrochloride occurs in white crystals, soluble in 20 parts of water, and in this way possesses decided advantage over phenacetine, which is soluble in 925 parts of water, as mentioned above. It, like phenacetine, is used as an antipyretic. Strictly speaking, it might more properly be considered under the hydrocarbons other than benzene, as both phenacetine and phenocoll contain more than six carbon atoms. However, as they so closely resemble acetanilide, it was deemed advisable to deviate from the regular order, that these closely similar bodies might be considered together. CHAPTER XLIV TOLUENE COMPOUNDS TOLUENE has the formula C,H,CH,. It represents benzene in which one hydrogen is replaced by a methyl group. In this body, therefore, we have a combination of the ring and chain compounds, the methyl group possessing nearly all the reactions of the chain series of hydrocarbons, while the phenyl acts exactly as it did in benzene. Toluene was first made by dry distillation of rosin by Pelletier and Walter in 1838. Deville (1841) obtained it by distillation of balsam. of tolu, and from this circumstance Berzelius named it toluol. It can be easily made by several reactions; chief among these are, (1) the Friedel Craft reaction, in which benzene is treated with methyl chloride in the presence of aluminum chloride, and (2) by the Fittig reaction, in which phenyl bromide is treated with methyl iodide in the presence of metallic sodium, this latter way being a modification of the Wuertz reaction mentioned on p. 634. These two reactions are mentioned by name because affording means of the manufacture of any of the hydrocarbons of this series. Thus if ethyl chloride is substituted for the methyl chloride in the first reaction, or if ethyl iodide replaces methyl iodide in the second reaction, we would get ethyl benzene, CH,C,H ̧. Most commercial toluene, however, is obtained by the fractional distillation of coal-tar, and is a colorless or amber-colored liquid, of aromatic odor, suggestive of benzene. It has a specific gravity 0.870, and boils at 110° C., and is insoluble in water, but freely soluble in alcohol. In its chemical behavior it resembles benzene, on one hand, and methane, on the other, and in the same way forms two distinct lines of hydrocarbon derivatives. Thus, the replacing of one hydrogen of the benzene group by the addition of chlorine gives rise to the compound known as monochlor-toluene, and this body is produced when chlorine is passed into cold toluene.. On the other hand, if boiling toluene is treated with chlorine, the halogen replaces one of the hydrogens of the methyl group, forming the body called benzyl chloride. The structural difference between these two bodies is best shown by the graphic formulas given below. These two compounds are mentioned not because of their importance in themselves, but by reason of the possible forms when the respective chlorines are replaced by hydroxyls, in the first case a phenol (cresol) being formed, whereas the benzyl chloride yields benzyl alcohol, which possesses all the char acteristics of an ordinary fatty alcohol. Under appropriate treatment of boiling toluene with chlorine, there is also yielded benzotrichloride, CH,CC,, and benzal chloride, CHCHCI,. The toluene derivatives of pharmaceutic interest are: OH The cresols, CH, are the monobasic phenols of toluene, and, like all di-derivatives of benzene, are known in the ortho-, meta-, and para- forms. A mixture [CH(CH2)OH] of the three isomeric Cresols obtained from coal-tar, freed from phenol, hydrocarbons, and water. It should be preserved in ambercolored bottles, protected from light. A colorless or straw-colored refractive liquid, having a phenol-like odor, and turning yellowish-brown on prolonged exposure to light. Specific gravity: 1.032 at 25° C. (77° ̊F.). Cresol is soluble in 60 parts of water at 25° C. (77° F.); miscible in all proportions with petroleum benzin, benzene, alcohol, ether, and glycerin; miscible with alkali hydroxide solutions. It boils from 195° to 205° C. (383° to 401° F.). If 1 Cc. of Cresol be mixed with 1 Cc. of an aqueous solution of sodium hydroxide (1 in 10), it should dissolve with no appreciable liquid residue (absence of or limit of hydrocarbons). If 1 Cc. of Cresol be mixed with 1 Cc. of glycerin, a clear solution should be produced, from which, on the addition of 1 Cc. of water, the Cresol should completely separate (absence of, and distinction from, phenol). Tests for Identity.-Given above. Impurities.-Hydrocarbons, phenol. Details above. Remarks. As mentioned in the official definition, commercial cresol (or cresylic acid, as it is frequently called) is a mixture of the three cresols mentioned above. It has been accorded pharmacopoeial recognition because a constituent of the new official, compound solution of cresol. It is sometimes used internally as an intestinal antiseptic. Dose.-0.05 Cc. (1 minim). LIQUOR CRESOLIS COMPOSITUS. Compound Solution of Cresol. Recipe.-Cresol, five hundred grammes.. 500 Gm. Linseed Oil, three hundred and fifty grammes.. 350 Gm. 80 Gm. To make one thousand grammes.. 1000 Gm. Dissolve the Potassium Hydroxide in fifty grammes of Water in a tared dish, add the Linseed Oil, and mix thoroughly. Then add the Cresol and stir, until a clear solution is produced, and finally sufficient Water to make the finished product weigh one thousand grammes. Remarks. This is a 50 per cent. solution of cresol in an alkaline linseed oil soap solution, and is a product therapeutically similar to the popular alkaline solutions of coal-tar distillates, such as creolin, lysol, Like these, it is used as an antiseptic wash or douche. I, Losophane, CH-OH, is cresol tri-iodide, contains 78.38 per cent. iodine, and CH, is used as an iodoform substitute. Europhene, CH, CH, CH, OH is di-isobutylorthocresol iodide. This name is inserted merely to show how simple it is to explain in words a graphic formula, a comparison of the formula just given with the name proving the fact. This body contains 28.17 per cent. iodine, and is used like aristol. Homopyrocatechin, so named because of its similarity to pyrocatechin, is the diatomic phenol of toluene. Its formula is C.H(OH), CH CH, Its methyl ester, CHOCH, is known as creosol, and is of interest OH as a constituent of creosote. CREOSOTUM. Creosote. A mixture of phenols and phenol derivatives, chiefly guaiacol and creosol, obtained during the distillation of wood-tar, preferably of that derived from the beech, Fagus silvatica Linné or Fagus ferruginea Aiton (Fam. Fagacea). An almost colorless, yellowish (not pinkish), highly refractive, oily liquid, having a penetrating, smoky odor, and a burning, caustic taste; it should not become brown in color on exposure to light. Specific gravity not below 1.072 at 25° C. (77° F.). Its solution in about 140 parts of water at 25° C. (77° F.) is not perfectly clear. With 120 parts of hot water it forms a clear liquid, which, on cooling, becomes turbid from the separation of minute oily drops (distinction from, and absence of, both phenol and so-called "coal-tar creosote"). The filtrate from these separated oily globules yields a reddish-brown precipitate with bromine T.S. (distinction from phenol and so-called “coal-tar creosote," both of which yield white precipitates). Soluble in all proportions in absolute alcohol, ether, chloroform, carbon disulphide, acetic acid, and fixed and volatile oils. When distilled, most of it comes over between 200° and 220° C. (392° and 428° F.). When cooled to -20° C. (-4° F.), it becomes gelatinous, but does not solidify (difference from phenol). It is inflammable, burning with a luminous, smoky flame. Creosote is neutral or only faintly acid to litmus-paper. On stirring together equal volumes of Creosote and collodion in a dry test-tube, no permanent coagulum should form (difference from phenol and so-called "coal-tar creosote," and limit of the former). If 1 volume of Creosote be mixed with 1 volume of 95 per cent. glycerin, a clear mixture will result, from which a creosotic layer, equal to or greater in volume than the Creosote employed, will separate on the addition of one-fourth volume of water (difference from, and limit of, phenols). On adding to 10 Cc. of a saturated aqueous solution of Creosote 1 drop of ferric chloride T.S., the liquid develops a clear violet-blue color, which is very transient; it then clouds almost instantly, the color passing rapidly from a grayish-green into a muddy-brown, with finally the formation of a brown precipitate (difference from phenol and so-called "coal-tar creosote," and limit of the former). If 1 Cc. of Creosote be mixed with 10 Cc. of a solution of potassium hydroxide in absolute alcohol (1 in 5), a solid crystalline mass will form (difference from phenol and so-called "coal-tar creosote," and limit of the former). |