913 



CINCHONA, ALKALOIDS OF. 



CINCHONA BARKS. 



914 



Gallate of quinine. This salt precipitates in the state of a white 

 powder, when a soluble gallate is added to a solution of a salt oi 

 quinine. It is soluble in hot water, but precipitates as the solution 

 cools ; it dissolves readily in excess of acid and in alcohol. This salt is 

 produced when infusion of galls is added to infusion of yellow bark. 



Kinate of quinine is the salt which exists naturally in the bark. It 

 is crystalline, and may be obtained by spontaneous evaporation in 

 mammellated white crusts, which sometimes consist of small needles 

 that lose their transparency by exposure to the air, and assume a horny 

 appearance. This salt is very bitter, slightly soluble in alcohol, but 

 very soluble in water. 



lodoquinine is obtained by rubbing together quinine and iodine. It 

 is a brown amorphous powder. 



Bundphate of mloquinine (C^H^N.,0,, I 2 , 2S0 3 , 2HO + lOAq.), called 

 Herapathite, after its discoverer, Herapath, is an exceedingly inter- 

 esting body, on account of its optical properties. It is readily obtained 

 by dissolving sulphate of quinine in concentrated acetic acid, and 

 adding an alcoholic solution of iodine to the liquid heated to 130. 

 On cooling, large rectangular plates form on the surface, and may be 

 removed by careful manipulation. By reflected light the crystals 

 appear of a brilliant green colour, by transmitted light of a pale olive, 

 while the whole of the light that passes through is perfectly polarised, 

 so that a second plate placed at right angles on the first as completely 

 prevent the passage of light as two plates of tourmaline, or Nichol's 

 prisms.* [POLARISATION.] 



2. Quinidine (G lo H. M N^O i + 4 Aq.) This alkaloid is isomeric with 

 quinine. It is best prepared from commercial quinoidine, by digest- 

 ing the latter for some time in boiling ether, filtering, evaporating the 

 solution to dryness, digesting the residue in dilute sulphuric acid, 

 decolourising with animal charcoal, and precipitating with ammonia. 

 A solution of the precipitate in a nu'xture of alcohol and ether yields, 

 on evaporation, large oblique rhombic prisms, which are at first quite 

 transparent, but soon effloresce and become opaque. I 



Heated to 320, quinidine loses its water of crystallisation and fuses, 

 solidifying on cooling to a resinoid mass. It is soluble in 1500 parts 

 of cold water, 750 of boiling water, 45 of cold absolute alcohol, 3'7 

 parts of hot ordinary alcohol, and 90 parts of cold ether. Its solution 

 in alcohol rotates a ray'of polarised light in a contrary direction to that 

 produced by solution of quinine. 



Quinidine combines with acids, forming a class of salts somewhat 

 similar to the corresponding salts of quinine. The neutral hydro- 

 chlorate contains one equivalent less of water than the quinine salt, 

 and the bihydmchlorate is far more stable than the bihydrochlorate 

 of quinine. The acetate, tartrate, and especially the oxalate, of 

 quinidine, are much more soluble in water than the analogous com- 

 ]Hinnds of quinine. 



3. L'inchonine (C^H^N^O.,) is produced, as before stated, in the 

 manufacture of sulphate of quinine ; or sulphate of cinchonine may be 

 obtained from pale or gray cinchona bark, by a process similar to that 

 for obtaining sulphate of quinine from yellow bark, and the alkaloid 

 separated by precipitation with ammonia. It is entirely purified from 

 quinine by taking advantage of the fact that it is less soluble in alcohol 

 than quinine, and that its sulphate is more soluble in water than 

 sulphate of quinine. 



Cinchonine crystallises in large, brilliant, colourless prisms. It is 

 almost insoluble in ether, slightly so in chloroform and the fixed and 

 efwenti.il oils, and soluble in the alkalies or their bicarbonates. Heated 

 to 329, it fuses and solidifies to a crystalline mass on cooling. In an 

 atmosphere from which oxygen is excluded, it may be sublimed with- 

 out decomposition. Its solution in alcohol produces dextrorotation 

 upon a ray of polarised light. 



The salts of cinchonine are formed, for the most part, in the same 

 way as the salts of quinine, than which they are more soluble both in 

 alcohol and in water. The ttsulphate (C^H^N.O,, 2HO, 2S0 3 + 6 Aq.) 

 forma very large, beautiful rhombic octohedra. The Ukydrocklorate 

 treated with bromine forms bromodnchonine (C^H^BrN^O,,). 



4. Cinehanidine (C. H !4 N.,O a ) bears the same relation to cinchomne 

 that quinidine does to quinine. It may be directly obtained from 

 Maracaibo or Bogota barks, by processes similar to those for obtaining 

 the other alkaloids. According to M. Pasteur, the quinidine of com- 

 merce usually contains a large quantity of cinchonidine. The latter 

 may be detected, on examination, by the transparency of its crystals 

 compared with those of quinidine, which rapidly become opaque on 

 exposure to the air. 



Crystallised from absolute alcohol, cinchonidine occurs in very 

 brilliant, anhydrous, rhomboidal prisms, very slightly soluble in water 

 or ether The alcoholic solution turns the plane of polarisation to the 

 left Heated to 347 the crystals melt; and at a higher temperature, 

 if in contact with air, burn with a smoky flame, exhaling the odour of 

 oil of bitter almonds. 



The salts of cinchonidine are obtained with equal facility to the salts 

 of quinine &c They are all more soluble in water thau the quinine 

 compounds, much more soluble in alcohol, but almost insoluble in 

 ether/ The neutral sulphate (C, H M N 2 !1 ,HO,S0 3 ) crystallises m 

 stellate groups of silky needles. 



For details of the manufacture of large available crystals, see a paper by 

 Dr. nerapath in the ' Pharmaceutical Journal, 1 vol. xiii. p. 378. 

 ARTS AHD SCI. DIV. VOL. II. 



Methylic nnd ethylic derii'atlre.i of the cinchuna alkaloids may be 

 obtained by directly combining the several bases with the iodides of 

 methyl and ethyl. They possess considerable theoretical interest. 



Chlorine and bromine derivatives of cinchonine have also been described ; 

 but for these and other less important compounds, &c., of the cinchona 

 bases, the reader is referred to Gerhardt's ' Traite 1 de Chimie Organique,' 

 tome iv. pp. 104-152. 



The tests by which the cinchona alkaloids may be distinguished 

 from each other are somewhat unsatisfactory, inasmuch as they do not 

 admit of being readily applied. Liebig proposes for this purpose to 

 take advantage of the difference of their solubility in ether ; for instance, 

 to detect the presence of cinchonine in the salts of quinine, 10 grains 

 of the latter are agitated with a quarter of an ounce of washed ether 

 and 20 drops of strong solution of ammonia ; on standing, the mixture 

 separates into two layers, the upper an ethereal solution of quinine, 

 the lower an aqueous solution of sulphate of ammonia, on which floats 

 any cinchonine that was present in the quinine salt. A test by which 

 to detect even a trace of quinine or quinidine in a solution, consists in 

 adding to it some recently prepared chlorine water, and then a few 

 drops of ammonia, when a green coloration is produced if either of 

 those alkaloids is present ; by this method one grain may be detected 

 in a gallon of water. Cinchomne and cinchonidine are not affected by 

 this test. Quinine may be distinguished from quinidine by the oppo- 

 site influence exerted by their solutions on plane-polarised light, the 

 former being powerfully Isevogyrate, the latter equally dextrogyrate. 

 Cinchonine under the same circumstances possesses dextrorotation, 

 cinchonidine Isevorotation : this test therefore, combined with the 

 chlorine and ammonia test, presents a means, less facile it is true than 

 could be wished, of discriminating between these four organic bases. 

 Dr. Herapath makes use of the difference in the optical properties of 

 the iodosulphates of the alkaloids, as a means of distinguishing them 

 from each other. 



Qtunicine and cinchonicine were mentioned at the commencement of 

 this article as products of the action of heat on the cinchona alkaloids ; 

 quinine and quinidine yielding quinicine, cinchonine and cinchonidine 

 furnishing cinchonicine. The precaution necessary to be observed 

 in the preparation of these substances, is to fuse the alkaloids at a 

 temperature below their decomposing point. This is accomplished by 

 mixing with a small quantity of water and sulphuric acid, and main 

 taining the mixture at a temperature of about 250 for three or four 

 hours. The change that occurs is entirely molecular, the composition 

 of the alkaloid being unaltered. 



The properties of quinicine and cinchonicine are, according to 

 M. Pasteur, very similar to those of the bases from which they are 

 obtained. They of course differ from each in chemical composition 

 to the same extent that quinine and its isomers differ from cinchonine 

 and its isomers, but otherwise they much resemble each other. Both 

 are very soluble in alcohol, and nearly insoluble in water, unite readily 

 with carbonic acid, expel ammonia from its salts, are precipitated from 

 their solutions in the form of resinous liquids, and finally both turn 

 the plane of polarisation to the right, though comparatively feebly. 

 They are equally bitter, and as febrifuges possess equal merits. 



Quinetine and cinchonetine are names given to the red products ob- 

 tained by the action of the puce-coloured oxide of lead on boiling 

 solutions of the acid sulphates of the alkaloids. They have not been 

 much investigated. 



Cinchmatine (C 4e H M N 2 8 ). An alkaloid discovered by Pelletier 

 and Corriol in arica cinchona baric, and called by them aricine. Mazzini 

 found it in the bark of Cinchona ovala, and gave it the name of cincho- 

 vatine ; the two are, however, identical. It is extracted in the same 

 manner as quinine and cinchonine. Cinchovatine is insoluble in water, 

 but dissolves in alcohol ; and the solution yields large colourless in- 

 odorous prisms, which after some time have a bitter taste. It has an 

 alkaline reaction. It melts at 370 Fahr. 



The salts of cinchovatine are soluble, and crystallise very readily, 

 especially on the cooling of saturated boiling solutions ; it is soluble in 

 ammonia, and crystallises from the solution by evaporation. The 

 action of concentrated nitric on cinchovatine is very characteristic ; it 

 dissolves, giving an intense green colouration. 



CINCHONA BARKS, Medical Properties of. The botanical cha- 

 racter of some of the most important species of cinchona, as far as 

 they were then known, as well as some of the commercial and pharma- 

 ceutical or officinal barks, have been given in NAT. HIST. Drv. 

 Since then, much valuable information has been acquired, chiefly by 

 Dr. Weddell, who spent two years in the cinchona forests of Bolivia and 

 a part of Peru, and who has embodied the results of his researches in 

 the splendid work, entitled ' Histoire Naturelle des Quinquinas,' Paris, 

 1849. To that book inquirers who demand full information must be 

 referred, as well as to Schleiden, ' Pharmacognosie, 1 the contributions of 

 Mr. J. E. Howard, to the ' Pharmaceutical Journal,' vols. xi., xii., xiv., 

 and to the ' Description of Pavon's Specimens in the British Museum," 

 by Mr. J. E. Howard, of which part i., has just appeared ; and chiefly 

 to the elaborate investigations of the late Dr. Pereira, in vol. ii., part ii., 

 p. 1605, 3rd ed. of his ' Elements of Materia Medica.' Lond. 1853. 



It is only necessary to remark here, that Weddell divides the so- 

 called species of cinchona of most former writers into two genera, 

 Chichona, Wedd. ; and Cascarilla, Wedd., the former comprising those 

 species the capsule of which dehisces from the. base to the apex (Qiu'n- 



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