FORMULA: HC7H5O2=C6H5COOH. MOLECULAR WEIGHT: 121.71.
SYNONYMS: Acidum benzoicum sublimatum, Flowers of benzoin, Flowers of Benjamin, Flores benzoes.
"An organic acid, usually obtained from benzoin by sublimation, or prepared artificially, chiefly from toluol. It should be kept in dark, amber-colored, well-stoppered bottles, in a cool place"—(U. S. P.).
Source and History.—Benzoic acid is a characteristic constituent of many balsam-resins. It is contained in benzoin, storax, liquidambar, castoreum, balsams of tolu and Peru, and other resinous bodies. The principal source, however, is from gum benzoin, though on account of the scarcity of benzoin yielding profitable quantities of the acid, Botany Bay resin is often used, and as a rule gives a larger yield than that obtained from true benzoin. There are two kinds of benzoic acid on the market, viz.: English and German. The former is obtained by sublimation of the above-mentioned gums; the latter from the urine of herbivorous animals and from coal-tar products. That made from benzoin only should be used by the druggist and doctor.
Vigenère, as far back as 1608, described benzoic acid as one of the products resulting from the dry distillation of gum benzoin. Lemery (1675), and Scheele, just 100 years later, both recognized it as an acid, and the process of preparation given by the latter is essentially one of the methods used in its production at the present time. It was discovered by Baron Liebig, in 1830, in the products obtained by distilling hippuric acid, and obtained from that acid by the action of acids and alkalies by Dessaignes in 1847.
Preparation.—Several modes of preparing benzoic acid have been given from time to time. We shall only introduce here one dry and one wet method. The dry method, which is essentially that introduced by Mohr and adopted by the Pharmacopoeia of the United States in 1870, is as follows: Into an iron dish about 8 or 9 inches wide and a couple of inches deep is introduced about 1 pound of benzoin, broken into coarse fragments or coarsely powdered, spread uniformly over the bottom of the vessel. Over the top of the dish is evenly stretched a piece of coarse filter-paper and pasted to the edges of the container. A hat-like, conical receiver is then made of well-sized paper, a little larger at the base than the diameter of the dish to which it is then attached by pasting it securely over the rim of the vessel. The dish, with its contents, is then placed in a sand-bath and gently heated not higher than 145° C. (293° F.) at the beginning, gradually raising the heat until 200° C. (392° F.) is reached. The vapors of the acid, which are held in combination with the resin, are thus liberated by the heat, and ascending pass through the bibulous paper and condense on the inside of the conical receiver, all empyreumatic oils being absorbed by the paper diaphragm as the vaporous acid passes through it. The heating should be continued 3 or 4 hours or until the acid vapors no longer rise. Should the paper diaphragm become clogged by the melting of the acid in any watery vapor that may be resent, it should be removed and a new one inserted in its place. It occasionally happens that by jarring, or by some other means the condensed acid adhering to the receiving-cap becomes detached and falls upon the filter-paper, and thus becomes contaminated with the empyreumatic products held by it and liquefies, thus impeding the further passage of the vapor. Should this occur the fallen portion should be resublimed to rid it of impurities and a new diaphragm introduced. To prevent such an accident a layer or two of gauze or linen may be stretched above the paper division so that any falling particles would be caught by it, thus preventing its reaching the contaminated bibulous paper. A yield of about 7 or 8 per cent is realized by this method. By breaking up the fused mass left in the container and subjecting it again to sublimation an additional quantity may be obtained. An earthenware vessel may be used instead of an iron one, and the mass may be heated on a common stove-plate if desired, but great care should be exercised that the gum be not too strongly heated.
Scheele's wet method consisted in boiling benzoin in water and milk of lime, separating the resulting calcium benzoate while hot by filtration, and precipitating from the solution the benzoic acid by means of hydrochloric acid. The product is sometimes sublimed to give the appearance of the acid made by the dry method. This process yields about 13 ½ per cent.
A commercial grade known as German benzoic acid is prepared by mixing the urine of horses and cattle with an excess of lime, and evaporating the solution to about one-twelfth of its bulk. The resulting calcium hippurate is then supersaturated with hydrochloric acid, liberating hippuric acid, which is purified by animal charcoal or other means. Hydrochloric acid is then added to the purified hippuric acid and boiled one-half hour, when benzoic acid and glycocoll (CH2NH2COOH) result. Benzoic acid obtained in this manner has a fetid, urinous odor, and is purified by recrystallization or by subliming it with a small quantity of benzoin. Benzoic acid is also cheaply produced on a large scale by synthetic methods from naphthalin (C10H8), a derivative of coal-tar, and from tolulol (C6H5CH3), one of the products of the distillation of wood and coal and a constituent of commercial benzin. The greater portion of the artificial product is now prepared from tolulol by converting the latter into benzo-trichloride and heating this substance with water under pressure. The following reactions take place: C6H5CH3+Cl6=C6H5CCl3+3HCl. C6H5CCl3+2H2O=C6H5COOH+3HCl.
Description and Tests.—"Benzoic acid occurs in commerce in white, or yellowish-white, lustrous scales or friable needles, odorless, or having a slight, characteristic odor resembling that of benzoin, and of a warm, acid taste; somewhat volatile at a moderately warm temperature, and rendered darker by exposure to light. Soluble, when pure, in about 500 parts of water, and in 2 parts of alcohol at 15° C. (59° F.), in 15 parts of boiling water, and in 1 part of boiling alcohol. Also soluble in 3 parts of ether, 7 parts of chloroform, and readily soluble in carbon disulphide, benzol, fixed and volatile oils, but sparingly soluble in benzin. Benzoic acid volatizes freely with the vapor of water. On heating it to 100° C. (212° F.) it begins to sublime. At 121.4° C. (250.5 F.) it melts, and at a higher temperature it is consumed without leaving a residue. The acid sublimed from benzoin has a lower melting point, and a greater solubility in water. Benzoic acid has an acid reaction. On heating benzoic acid gradually with 3 parts of freshly-slaked lime in a retort benzol is evolved. The acid is freely soluble in solutions of alkali hydrates. On carefully neutralizing such a solution, and adding ferric chloride T.S., previously diluted with 2 volumes of water, and neutralized, if necessary, by ammonia, a flesh-colored precipitate of ferric benzoate is produced. A solution of benzoic acid in pure, cold, sulphuric acid, when gently warmed, should not turn darker than light brown; if it is then poured into water the benzoic acid should separate as a white precipitate, and the liquid should be colorless (absence of readily carbonizable, organic matters). If 0.5 Gm. of the acid and 0.8 Gm. of calcium carbonate be mixed with a little water in a crucible, the mixture dried, gently ignited, and then dissolved in water, with the aid of nitric acid in slight excess, so as to obtain 20 Cc. of filtrate, the addition of silver nitrate T.S. to the latter should not produce much more opalescence (if at all) than is produced by the same reagent in a solution measuring 20 Cc. prepared by dissolving 0.8 Gm. of the same calcium carbonate in water with the aid of nitric acid (absence of more than traces of chlorine). On warming 0.5 Gm. of the acid with 5 Cc. of water and 0.5 Gm. of potassium permanganate in a test-tube loosely stoppered and placed in a water-bath heated to about 45° C. (113° F.), then tightly stoppering and cooling the test-tube with cold water, upon removing the stopper no odor of oil of bitter almond should be discernible (absence of cinnamic acid)"—(U. S. P.).
Benzoic acid is permanent at ordinary temperatures. If made from hippuric acid its appearance is often as fine, if not finer, than when produced from benzoin, but traces of a urinous odor can be detected in it. If the odor of benzoic acid resembles that of the sweat of horses it should be rejected. German benzoic acid is often a pure white, the object in later years having been to make it so that it will resemble that produced from the gum. Formerly the crystals produced by this process (artificially) were much the handsomest. It will be observed that though the Pharmacopoeia recognizes both the natural and artificial product its description of the acid is so constructed that it can apply only to the true product produced from the gum, thus practically ruling out the artificial acid. Benzoic acid gives rise to a line of more or less soluble salts known as benzoates.
Action, Medical Uses, and Dosage.—Benzoic acid is destructive to bacterial forms of life, and equally as valuable as salicylic acid in arresting putrefaction. Infusion of gentian, orange, and buchu may be kept unimpaired for a month by the addition of ¼ gr. to the ounce of liquid (Benger). In bulk or in concentrated solution it acts, even in small doses, as a gastro-intestinal irritant, consequently it should be administered in large quantities of water. It excites a general sense of warmth throughout the system, and materially increases the secretions of the skin and pulmonary mucous surfaces. It was formerly used to a considerable extent, in broncho-pulmonary affections. Its principal use now, however, is in disorders of the urinary tract. It prevents and corrects ammoniacal and other varieties of fermentation of urine in the bladder and renders the fluid more acid. If, however, the urine be excessively acid its use, by dissolving it in water by the aid of a small amount of sodium phosphate or carbonate, renders it less acid and thereby relieves the irritability of the cystic mucous lining. It is a certain remedy for phosphatic gravel, and is said to be equally serviceable when vesical irritability is due to excess of uric acid. Cystitis, when due to excessively alkaline urine, or to a urinous fermentation, purulent or non-purulent, is promptly benefited by this agent. Its action is purely local, and by thus acting as an anti-ferment it renders good service in nocturnal enuresis, dysuria, and urethritis when due to these fermentative changes. It is a good remedy for gonorrhoea when aggravated by ammoniacal or other putrid states of the renal secretions. It prevents the formation of incrustations, or calculi of ammoniaco-magnesian phosphate, by maintaining the acid quality of the urine. The enuresis of children and urinal dribbling of old persons, if due to excessive alkalinity, are greatly benefited by a couple of 5 to 10-grain doses daily. Prof. Scudder recommends it as a specific in "irritation of the sympathetic and spinal system of nerves with uric acid deposits" and as a stimulant for brain exhaustion in mentally overworked individuals, with phosphuria—(Specific Medication). It is useful in rheumatism, but only in those cases showing markedly alkaline urine. It is believed to exert some influence on jaundice, due to obstruction of the bile ducts with inspissated bile, and has restored to its normal condition urine that was loaded with chyle. Benzoic acid reduces the quantity of albumen in albuminuria. It is one of the ingredients of paregoric, and is also employed in making many cosmetic washes. The dose ranges from 1/20 to 30 grains, the moderate doses being preferred to correct excessive alkalinity of the urine.
Specific Indications and Uses.—Excessively alkaline urine; phosphuria; vesical irritability, with alkaline urine; fermentative urine; brain-fag, with phosphuria; "irritation of the sympathetic and spinal system of nerves with uric acid deposits"—(Scudder).
Derivative.—BENZOYL TROPEINE (C15H19NO2.2H2O). Silky needles obtained by heating to 100° C. (212° F.) a mixture of tropine, benzoic acid, and dilute hydrochloric acid. It melts at 58° C. (136.4° F.); the anhydrous base at 41° to 42° C. (105.8° to 107.6° F.). Its compounds are not readily dissolved. Filehne (1887) found benzoyl-tropeine to effect a powerful local anaesthesia, and like other tropeines the muscles of accommodation and the pupils were affected by it. He also found other compounds of benzoyl to produce local anaesthesia, benzoyl morphine being weakest, benzoyl quinine more powerful, while benzoyl triacetonalkamine was most active in this respect.