4 68 



THE TROPICAL AGRICULTURIST. [December i, 1884. 



1S69) bad afresh affirmed to the quinologist Weddell* the 

 experimental law at that time generally held to be correct, 

 that the cinchona alkaloids were peculiar to the cinchonas 

 only, it may be assumed that Howard first bad his atten- 

 tion drawn to the presence of quinine in the bark in 

 question by my discovery, which Fliiekiger had communicated 

 to him privately. 



Far more important than this point is the question 

 whether the alkaloid of cuprea bark then spoken of as 

 quinine was quinine, or only an alkaloid similar to it, 

 homoquinine. Notwithstanding that at the time I found 

 the alkaloid in question to correspond in every respect 

 with quinine obtained from true cinchona bark, I have 

 once more examined the original cuprea bark in connec- 

 tion with my experiments upon homoquinine, the former 

 results being confirmed most completely. Subsequently, 

 also, it was pointed out by me that in cuprea bark quinine is 

 not accompanied by cinchonidine, which has equally been 

 since confirmed by D. Howard and others. On the other 

 hand, according to my observation, quinine is always present 

 in cuprea bark, although the quantity is sometimes relatively 

 very small. 



The constant occurrence of quinine in cuprea bark and 

 the persistent absence from it of cinchonidine is so far 

 of special interest that it has been assumed in several 

 quarters, especially by J. E. Howard.f that the plants in 

 their development and growth are capable of converting 

 quinine and cinchonidine into one another. Of course in 

 order to make this conversion preceptible certain influences 

 on the development of the plants or their cultivation at 

 different altitudes are required. Nevertheless, the assump- 

 tion of such a change as this during the development 

 and growth of the plant proves faulty, since if such a 

 conversion actually took place under the conditions named, 

 it would certainly be possible to discover a sample of cuprea 

 bark in which at least traces of cinchonidine would be 

 present. 



Although I am in the position to detect the smallest 

 traces of cinchonidine with quinine, all the experiments 

 made in this direction with cuprea bark, as well as with 

 quinine obtained from that bark, have remained without 

 Shi cess, a result that justifies me in saying that the form- 

 ation of the quinine within the plant takes place quite inde- 

 pendently of the cinchouidine. 



( in account of the absence of. cinchonidine it is very 

 easy to prepare pure quinine sulphate from cuprea bark. 

 This has normally, whilst yet uneffloresced, the composition 

 represented by the formula (O a0 H M N 2 O,),, S0 4 H s + 8 H a O, 

 like the similarly pure salt obtainable From cinchona barks.* 

 The possibility is not, however, excluded that the com- 

 mercial sulphate obtained from cuprea bark may contain 

 somewhat less than eight molecules of wate r of crystalliz- 



* Uebersicht J. Cinchonen, "Weddell, 7. 



t Pitarni. Journal, [31, xiii., 1013. 



\ With respect to the remark of Fliiekiger upon this 

 salt ('Die Ohinarinden,' 18S3, p. 55), that "it is not 

 established whether this salt contains seven or eight mole- 

 cules of water of crystallization, or possibly a quantity 

 lying between the two," I may say that more than twenty 

 years since (Anna/en, cxix., 361) it was shown by Jobstaud 

 myself that the formula (C^HmNjO^, S0 4 H a « 7H s O, for 

 quinine sulphate, is incorrect. On the other hand, it is 

 not so easy to say whether the sulphate in question con- 

 tains seven and a half or eight molecules of H.,0. A series 

 of experiments, however, carried out by me with every 

 precaution, showed that pure uneffloresced sulphate may 

 actually contain eight molecules of water of crystallization. 

 In that case the formula attribute.! to quinine sulphate 

 by Robiquet about fifty years ago would be correct. 

 Undoubtedly the commercial sulphate may contain generally 

 less water than is required by the formula (O 20 H i , 4 N.,O a ) 2 , 

 S0 4 H 2 X 8 H,0., and for this reason, that in manufacturing 

 operations it is almost impossible to prepare it dry and 

 avoid at the same time the occurrence of a partial efflorescence 

 of the salt. Quite apart from the fact that in certain 

 quarters a smaller amount of water (for instance, 14J per 

 cent) in quinine sulphate is required, it should not be 

 overlooked that a commercial sulphate corresponding to 

 the legally prescribed tests of the German Pharmacopoeia 

 may sometimes contain quite a considerable quautity of 

 cinchonidine sulphate (Annalcn, ccv., 222), upou which a 

 deficiency in water of crystallization may equally depend. 



ation, not only because it has effloresced more or less, but 

 also because it contains an admixture of homoquinine. 



//. — Homoquinine. 

 The occurrence in cuprea bark of a special alkaloid, similar 

 in many respects to quinine, was announced simultaneously, 

 in December, 1881, by D. Howard and Hodgkin,* Paul 

 and Cownley,t and G. Wniffen,} the alkaloid being named 

 by the first two chemists "homoquinine," and by Whiffen 

 " ultraquinine." The name "cupreine" has also been 

 suggested for it. This same alkaloid was also observed 

 by one of my colleagues a year earlier; but he considered 

 it to be cinchonidine until June, 1881, when he became 

 aware of the error. 



According to Tod the alkaloid in question first appeared 

 in cuprea bark in September, 1880, but only in a few specim- 

 ens of bark ; its occurrence first became almost general 

 in May, 1881. The amount of homoquinine in the bark 

 in many cases reached 03 per cent, in some 0'5 to 0'6 

 per cent. According to 'Whiffen the cuprea bark examined 

 shortly before the publication referred to contained Ol 

 to OS per cent of the alkaloid, and he believed that in 

 greater or less quantity it was to be met with in every 

 cuprea bark. Paul and C'ownley first observed it very 

 frequently four months before their communication (con- 

 sequently first in August, 1881). D. Howard, who appears 

 not to have observed it so frequently as Paul and Cowuley, 

 states that the quantity of homoquinine in the barks in 

 question amounted to about 10 per cent of their quinine 

 contents, consequently to about 02 per cent. Finally to 

 complete the history of our alkaloid it may be mentioned 

 that Wood and Barret § were unable to observe this alkaloid 

 in several hundred specimens of cuprea bark which they 

 examined specially for the purpose, and they believed that 

 it might be a compound of quinine with conchinine. 



With respect to this latter point, my examination of 

 the alkaloid prepared by Tod, as well as of some kindly 

 supplied to me by Paul and C'ownley, has shown that 

 this material is free from conchinine. Moreover the state- 

 ment made by "Whiffen, as well as those of Howard and 

 Hodgkin, point to the same conclusion, so that the opinion 

 of "Wood and Barret referred to would appear to be without 

 support, quite apart from the fact that I have been un- 

 able to obtain any such compound of quinine and conchinine 

 in working according to the directions originally given by 

 those chemists. 



All the above-named chemists who have indicated the 

 existence of homoquinine in one way or another are unan- 

 imous that the alkaloid in question forms with sulphuric 

 acid a neutral salt rather difficulty soluble in cold water; 

 it is presumed consequently that it would be necessarily 

 mixed with quinine sulphate prepared from the particular 

 bark, since it would not be separated or altered in any 

 way during the manufacture of quinine. 



According to my experience the best method of separating 

 homoquinine from such a mixture is by dissolving it in 

 dilute sulphuric acid, precipitating the alkaloids with am- 

 monia and at once shaking them out with ether, from 

 which after a short time the homoquinine separates out in 

 crystals. The. crystallised homoquinine, after being separated 

 as completely as possible from the mother-liquor, is re- 

 dissolved in dilute sulphuric acid, and again precipitated 

 with ammonia and taken up with ether, which quickly 

 deposits the alkaloid in crystals. This operation is repeated 

 as often as may be necessary, but generally a second re- 

 erystallizatiou of the base in this way suffices to separate 

 any admixture of quinine. 



On a previous occasion, || I had, upon the basis of the 

 results of analyses I. and II., which were before me at 

 the time, represented homoquinine by the formula O l9 H 28 

 No0 2 . But in the course of this investigation it has giveu 

 weighty evidence in favour of the formula (!.,„H, J N.,Oj, 

 with which, moreover, analysis IV., made by nie only recently 

 with well crystallized material, corresponds very well. Before 

 analysis the substance was dried at 120 ° to 125 ° C. ; it 

 then gave: — 



* Plutrm. Journ., i:i], xii., 528. 

 t Pliurm. Journ., [3], xii., 497. 



* I'liarm. Journ., [3], xii., 565. 

 § Chemical News, xlv.. 6. 



jl Berichte, xv.. 857. 



