The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan.

  • Buttle, G. A. H. (Gladwin Albert Hurst), 1899-1983.
Date:
[1934]
Catalogue details

Licence: Public Domain Mark

Credit: The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan. Source: Wellcome Collection.

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    ammonia test, which probably does not detect less than 2 % of cinchonidine, and the polarimetric test, which is of no value for the present purpose, since quinine is contaminated not only with cinchonidine, but also with the optically active bases, dihydro quinine and dihydro cinchonidine. Cinchonidine is less soluble in benzene than quinine, whilst its acid salts are more soluble in water than those of quinine: there is no reason to doubt that by rejection of appro¬ priate fractions in fractional crystallisation from such solvents the small amount of cinchonidine in commercial quinine is eliminated. The detection of cinchonine in quinidine is also difficult; there is a con¬ siderable difference between the optical rotations of the two alkaloids, but there has been until now no method of distinguishing between cinchonine and dihydro- quinidine as the cause of low rotation in commercial quinidine. Cinchonine is less soluble in alcohol than quinidine and, it is shown later (p. 434) that it can be eliminated from crude quinidine by recrystallisation from boihng alcohol, the first fractions being rejected and any traces that escape in this process being left in the mother-liquors in the final fractionation, cinchonine dihydrochloride being much more soluble in water than quinidine dihydrochloride. Elimination of dihydro-bases. The second group of impurities consists of the naturally-occurring dihydro-alkaloids, each primary alkaloid being accompanied by its own reduction product. The vinyl group in each of the parent bases is readily oxidised to a carboxyl group by permanganate, while the reduced bases are relatively stable to this reagent, and this method has hitherto been used both for the isolation of these dihydro-bases and for their estimation. Since the dihydro-bases are only relatively stable to permanganate, such a method can merely give approximate results and for the detection and estimation of the dihydro-bases, the authors have used a new method, viz. catalytic hydrogena¬ tion in an apparatus designed for quantitative work [Paget and Solomon, 1932]. The errors in such a determination are estimated not to exceed ±1 %, and a primary cinchona alkaloid has been regarded as free from its dihydro-base when it absorbed 99-5 to 100-5 % of the quantity of hydrogen required to convert the vinyl group into an ethyl group. Colloidal palladium on barium sulphate or Adams’s platinic oxide has been used as a catalyst, the former being preferred as it is less liable to form colloidal solutions from which the reduction product is difficult to recover. For the estimations, 0-4 to 0-5 g. of the base or one of its salts dissolved in 10 ml. of A/10 sulphuric acid, containing 0-05 g. of palla- dised barium sulphate, is exposed to hydrogen with constant, vigorous me¬ chanical agitation. Absorption is rapid during the first half hour and finishes in about 2 hours after which it is taken as complete if, during a further 2 hours, the change in volume of gas is not greater than 0-1 ml. If, after this point is reached, action is continued, there is a slow absorption of 0-2 to 0-5 ml. per diem due no doubt to the very slow formation of more highly hydrogenated bases, but there is no practical difficulty in determining the point at which rapid formation of the dihydro-base is complete and the second very slow absorption begins. The results for hydrogen absorption given below are corrected for hydrogen absorbed by the catalyst, which must be determined by blank experi¬ ments on each new batch of catalyst made. The bulk samples of dihydro-bases used were made by catalytic hydrogena¬ tion in like manner of the purified primary alkaloids and were crystallised as bases or salts to constant optical rotation. As so much attention has been given to the permanganate test for the dihydro-bases, it was thought desirable to use this in a more or less quantitative form. For that purpose, 5 ml. of a 2 % solution of the dihydro-base in water containing 0-3 ml. of A sulphuric acid was