Related entry: Piper (U. S. P.)—Piper
FORMULA: C17H19NO3. MOLECULAR WEIGHT: 284.38.
"A neutral principle obtained from pepper, and obtainable also from other plants of the natural order Piperaceae"—U.S. P.).
Source, History, and Preparation.—Piperin, the active principle of pepper (see Piper), exists in the black, white and long pepper, and in the berries of Cubeba Clusii, Miquel. It was first obtained by Oersted, of Copenhagen, in 1819, who believed it to be an organic base. Pelletier (1821) proved, however, that it is a non-basic principle. It may be isolated by various methods. According to Cazeneuve and Caillol (Jahresb. der Pharm., 1877, p. 68), powdered pepper is mixed with milk of lime, the mixture evaporated to dryness on the water-bath, and extracted with ether. This solvent upon evaporation leaves piperin in the form of impure crystals, which are purified best by crystallization from acetone (Flückiger, 1891).Sumatra pepper yielded Cazeneuve, on an average, 8.10 per cent; Singapore white pepper, 9.15 per cent of piperin. T. Stevenson (see Amer. Jour. Pharm., 1885, p. 513) prepares an extract from 50 grammes of pepper with methyl alcohol, dissolves out the resinous portion by means of potassium carbonate; the residual piperin is washed with water and recrystallized from alcohol.
Description and Chemical Composition.—Piperin (C17H19NO3) is described by the U. S. P. as forming "colorless or pale yellowish, shining, prismatic crystals, odorless, and almost tasteless when first put in the mouth, but on prolonged contact producing a sharp and biting sensation. Permanent in the air. Almost insoluble in water; soluble in 30 parts of alcohol at 15° C. (59° F.), and in 1 part of boiling alcohol; very soluble in hot acetic acid; only slightly soluble in ether. When heated to 130° C. (266° F.) piperin melts; upon ignition it emits alkaline vapors, and is consumed, leaving no residue. The alcoholic solution of piperin is neutral to litmus paper. Concentrated sulphuric acid dissolves piperin with a dark blood-red color, which disappears on dilution with water. When treated with nitric acid, piperin turns rapidly first orange and then red, and the acid acquires a yellow color, deepening to reddish as the crystals dissolve. On adding to this solution an excess of potassium hydrate T.S., the color is at first yellow, but upon boiling it becomes blood-red"—(U. S. P.). Piperin is also soluble in chloroform, benzol, carbon disulphide, but almost insoluble in petroleum ether. Piperin has only weak basic properties, being hardly soluble in dilute acids. With hydrochloric acid and platinic chloride, however, it forms a well crystallizable double salt. Piperin is not decomposable even by boiling solution of caustic potash (Gerhardt); but prolonged heating with alcoholic solution of caustic potash decomposes it into piperidine and the potassium salt of piperic acid (v. Babo and Keller), according to the following equation: C17H19NO3+KOH=C12H9O4K+C5H11N. Piperin, reversedly, was synthesized from these constituents by L. Rügheimer (1882). Piperic acid (C12H10O4), being nearly insoluble in water, may be precipitated from the solution of its potassium salt by the addition of hydrochloric acid, and recrystallized from alcohol. The acid forms yellow crystals, melting at 150° C. (302° F.). According to Fittig and Mielck (1869), it has the formula: CH2:O2:C6H3.CH:CH.CH:CH.COOH. The potassium salt by oxidation yields piperonal (which see). Piperidine (C5H11N) is a volatile, strong base, which may be separated in the above reaction by distillation with steam and collecting the vapors in dilute acid. It has the odor of ammonia and pepper, and forms well crystallizable salts with acids. Ladenburg, in 1885, succeeded in obtaining piperidine by synthesis, proving it to be hexa-hydro-pyridine (C5H5N.H6, or CH2:[CH.2CH2]2:NH).
Action, Medical Uses, and Dosage.—Formerly this agent was frequently substituted for or used in conjunction with the cinchona alkaloids in the treatment of malarial fevers. Piperin is now occasionally employed in intermittent fever, but will be found less efficient than the alcoholic extract of black pepper. Its use has also been advised in colic, diarrhoea, cholera, scarlatina, chronic gonorrhoea, and in solution as a wash for tinea capitis. Piperin should not be administered with astringents, as it is thereby rendered nearly inert. The dose is 1 to 8 grains, 3 or 4 times a day (see Piper).
Derivative of Piperin.—PIPERONAL, or HELIOTROPIN (C6H6O3). This compound is an aldehyde, the methylene ether of protocatchuic aldehyde, and has the formula: CH2:O2:C6H3.CHO. Its corresponding acid (CH2:O2:C6H3.COOH) is called piperonylic acid. Piperonal is obtained by oxidizing the potassium salt of piperic acid (see Piperinum; also see Piper Methysticum) with potassium permanganate in neutral solution. It forms small, white crystals, soluble in alcohol and ether, but sparingly soluble, in cold water (1 in about 600). It resembles coumarin and vanillin in odor, and is now manufactured for purposes of perfumery; but it has also been given medicinally in 10 to 15-grain doses, every 3 hours, as an antipyretic and an antiseptic.