layer, containing coloring matter, resin, fat, gallic and ellagic acids, is removed and the aqueous fluid, after concentration, under reduced pressure, in a still, to a syrupy consistence, is spread, when cool, on tin plates, which are placed on a steam table and covered with a wooden box; this causes the tannin to puff up and dry and gives rise to the peculiar spongy character of commercial tannin. The so-called crystalline tannic acid of German manufacturers is obtained by introducing a very thick syrupy mass, prepared as above stated, into well-tinned copper vessels, with a perforated bottom, through which the mass slowly drops in long threads on to heated revolving cylinders, where it dries, and is removed in the form of thin, needleshaped particles.

Another plan is to extract the powdered nutgall with a mixture of ether four parts and alcohol one part, transferring the tannic acid to water by agitation with the latter, and then proceeding as before stated. This method is extensively employed.

Diluted alcohol is used in the preparation of alcohol-tannin by percolation, the tincture being concentrated and evaporated to dryness in a vacuum apparatus. Water-tannin is obtained by evaporating the aqueous infusion described above, to dryness, in a vacuumpan. Neither of these products is as free from color or impurities

as the first named or ether-tannin.

In 1893 Prof. Trimble suggested the use of acetone for the extraction of tannic acid from nutgall, and exhibited, at Chicago, a sample of the acid, almost white, prepared by this method. The advantages claimed for this solvent are cheapness, thorough penetration, and rapidity of action.

Glucose, the most persistent impurity found in tannin, can be removed completely, as suggested by Trimble, by treatment with lead acetate and hydrogen sulphide and subsequent extraction of the tannin with acetic ether.

Gallotannic acid differs markedly from oak-bark tannins in its behavior toward several reagents, thus, while with lime water oaktannins give a pink or red precipitate, gallotannic acid causes a blue precipitate; with bromine water gallotannic acid gives no precipitate, while oak-tannins cause a yellow precipitate; ferric chloride and ammonium hydroxide cause a green precipitate with oak-tannins and a blue one with gallotannic acid, etc. The blue color sometimes observed in the case of oak-tannins with ferric salts is due to the presence of a foreign substance, pure oak-tannins showing only a green color. (Trimble.)

Owing to the ready discoloration of tannic acid by metallic iron in the presence of moisture, all contact with spatulas under such conditions must be avoided. Solutions of tannic acid change readily, particularly if exposed to air and light, gallic acid and probably ellagic acid, CH,O,, being gradually formed; such changes are retarded and even prevented by the presence of glycerin or alcohol in sufficient quantity.

The term tannin is now applied to the whole group of vegetable astringents, while the name tannic acid has been reserved for the particular product derived from nutgalls. The classification adopted by Trimble divides all tannins into two main groups, which may be distinguished from each other by the reactions above mentioned. All tannins should be soluble in water and precipitated by gelatin. The gallotannic-acid group includes, besides nutgall tannin, the tannins found in chestnut wood, chestnut bark, pomegranate bark, and sumac, while the oak-tannin group comprises the tannins from different species of oak, from kino, catechu, krameria, tormentil, mangrove, and canaigre.

While, for technical purposes, the estimation of tannin in various tanning materials is often of importance, and is no doubt also valuable in chemical plant analysis, such determinations are not required in pharmacy. Advantage is taken of the well-known property of tannin to form insoluble compounds with gelatin (as demonstrated in the preparation of leather), and this operation is included in all methods of assay thus far published. A complete account of Löwenthal's method for estimating tannin, as modified by Von Schroeder, will be found in the National Dispensatory, 5th edit., p. 108.

6

Tartaric Acid, H,C,H,O, or (CHOH),(COOH)2.-This acid is even more widely distributed in the fruit of many plants than citric acid, occurring both in the free and combined state. For commercial purposes, it is obtained from crude or partially purified argols (see p. 493) by neutralizing the acid potassium tartrate in hot solution with chalk, whereby calcium and potassium tartrates are formed, and then decomposing the remaining potassium tartrate with calcium chloride; the resulting calcium tartrate is washed with water until tasteless and decomposed by digestion with sulphuric acid, when sparingly soluble calcium sulphate is formed and tartaric acid liberated, which latter enters into solution. After removal of the precipitated calcium sulphate by filtration, the solution of tartaric acid is concentrated and allowed to crystallize, the crystals, if necessary, being redissolved, digested with animal charcoal, and recrystallized. Tartaric acid is rarely found in the shops in other than powder form, and, as a rule, is free from impurities. The official test for oxalic and uvic acids, by means of calcium sulphate solution, depends upon the insolubility of calcium oxalate and uvate in the presence of ammonium salts, whereas calcium tartrate is but slowly deposited under like conditions; an excess of ammonia must be avoided, hence the Pharmacopoeia directs incomplete neutralization. If crystallized tartaric acid is contaminated with uvic acid, the latter is readily detected by the milk-white appearance of its crystals, those of tartaric acid being translucent.

9

Valerianic Acid, HC,H,O, or (CH),CH.CH.COOH.-As this acid occurs in a free state in valerian root, it may be obtained by

distilling the root with water, neutralizing the aqueous portion of the distillate with soda, and decomposing this solution with sulphuric acid; it may then be purified by fractional distillation.

Commercially the acid is made by oxidation of amyl alcohol with a mixture of potassium dichromate and sulphuric acid, and neutralizing the distillate with sodium hydroxide; the resulting sodium valerianate is decomposed by means of sulphuric acid, when the liberated valerianic acid will rise as an oily layer. This is then freed from water by treatment with sulphuric acid, and carefully distilled. The reaction taking place may be illustrated thus: 3CH1OH 2K,Cr2O, + 8H2SO, 3HC,H,O2 2K2SO, + 2Cr,(SO4)3 11H2O. Since a small portion of the amyl alcohol escapes oxidation, it is attacked by the newly formed acid and passes over into the distillate as a compound ether, known as amyl valerianate, CH,CH,O,; the name apple oil is given to this ether, on account of its apple-like odor when diluted. When the acid distillate is neutralized with soda the amyl valerianate separates as an oily liquid, and may be removed.

=

2

The solubility of valerianic acid in not less than 26, and not requiring over 30 times its weight of water, affords a ready means of discovering certain impurities; it should also produce a clear solution with a slight excess of ammonia water.

The only use made of valerianic acid in pharmacy is for the production of ammonium valerianate in the manufacture of the elixir of the same name.

CHAPTER LX.

ALKALOIDS.

THE name alkaloids is applied to a large class of carbon compounds containing nitrogen, which are capable of neutralizing acids and forming salts. The basic properties of these compounds vary in intensity, some exhibiting but a feeble basic reaction, while others are capable of decomposing heavy metallic salts with the formation of metallic hydroxides. The term alkaloid was given to these so-called organic bases on account of their similarity in chemical character to alkalies, alkaloid meaning alkali-like.

Since the discovery of basic principles in both living and dead animal tissues the name alkaloids has generally been restricted to those nitrogenous bases derived from plants, the term leucomaines having been selected for the basic substances found in living animal tissues and płomaines for those produced during putrefaction of dead animal tissues; the last named are still sometimes called cadaveric alkaloids. Chemists go even a step further by subdividing vegetable bases and reserving the name alkaloid for all those shown to be derived from pyridine, CH,N, or quinoline, C,H,N, two simple bases found in coal tar.

The discovery of alkaloids occurred early in the last century, when Sertürner, a German apothecary, in 1817, demonstrated the basic character of a substance obtained by him, in 1806, from opium, now known to us as morphine. In order to distinguish the basic from neutral vegetable principles a different terminology has been adopted for the two classes, which has been maintained in the Pharmacopoeia and serves an excellent purpose. The ending ine (Latin ina) is applied to all basic plant products, while the ending in (Latin inum) is given to all neutral principles.

Alkaloids may be divided into two main classes as regards their constitution, namely, those containing carbon, hydrogen, nitrogen, and oxygen, and those containing only the first three elements; to the former, which are always solid, the name amides has been given, while the latter, which are liquid, are known as amines. Vegetable bases do not all possess the same saturating power, for while the majority are monacid in their character, several well-defined diacid bases are known. When brought together with acids they do not, like inorganic bases, cause the displacement of basylous hydrogen with the formation of water, but behave like ammonia, forming salts by simple addition. In regard to the naming of salts formed by the union of alkaloids with acids, it is customary in the case ( 697 )

of oxygen acids to follow the usual rule, thus: acetates, citrates, nitrates, phosphates, sulphates, etc., but, in the case of halogen acids, the proper name would seem to be obtained by changing the termination ic of the acid into ide for the salt, thus hydrobromide, hydrochloride, hydrocyanide, etc.; the Pharmacopoeia has, however, adopted the plan of using the termination ate throughout, no matter what acid is in combination.

In a pure state alkaloids, with a few exceptions, are but sparingly soluble in cold water, but dissolve more or less readily in alcohol, chloroform, petroleum benzin, benzene, amyl alcohol, etc.; some, but not all, dissolve in ether. Salts of the alkaloids, as a rule, are soluble in water, but less so in other solvents.

In nature alkaloids rarely occur in a free state, being usually associated with an acid, which, in some instances, is a peculiar acid characteristic of the plant in which it is found, as quinic acid of the cinchona barks, meconic acid in opium, etc.; many alkaloids occur in the plant as tannates. Alkaloids are not always restricted to special parts of the plant; while present to a much larger extent in some parts than in others, they are frequently met with in the root, stem, leaf, and fruit of the same plant. For their extraction various methods are employed: either the finely comminuted drug is exhausted with acidulated water, whereby the alkaloid is brought into solution as a new salt, which can then be decomposed and precipitated by means of an alkali and further purified by resolution in some appropriate solvent, filtration through animal charcoal, and crystallization; or the drug may be exhausted with a neutral solvent, such as alcohol or diluted alcohol, the resulting tincture being acidulated, evaporated to remove fats, resins, etc., filtered, treated with water, and precipitated and purified as stated above. Advantage is taken of the difference in solubility between free alkaloids and their salts to separate and purify the product by the use of immiscible solvents, such as water and petroleum benzin, water and chloroform, water and ether, etc., whereby the alkaloid can be alternately transferred, in a combined or free state, from one fluid to another; this necessitates, of course, provision for bringing the liquids into intimate contact by agitators. This method, which is extensively employed in the assay of alkaloidal drugs, is termed by analysts the "shaking out process," because, on a small scale, the transfer is made in glass separators by rotation or shaking. In large operations, such as the manufacture of the cinchona alkaloids and others, kerosene or gasolin, closely allied to benzin, is now extensively employed on account of its solvent capacity, its cheapness, and ready separation from watery fluids. In the case of alkaloids which are volatile, the drug is placed in a still with some water, and, by the addition of a fixed alkali, the alkaloid is liberated, and, with the aid of heat, passed over into a receiver containing acidulated water, when, having been obtained as an acid salt, it can be further purified and isolated by one of the methods before mentioned.