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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    treated with 0-5 ml. of xV 50 potassium permanganate. The colour disappears in not less than 10 minutes with all the dihydro-bases except dihydrocinchonine, which discharges it in 30 seconds. The specific rotations of the pure bases and their salts are recorded in Tables III and IV. It is well known that in this series the specific rotation varies with the nature of the solvent and the concentration of the solution. As the authors had to make extensive use of polarimetric observations to follow the course of crystallisation in the final purification of the alkaloids, they found it convenient to use xlf/40 solutions of any salt selected for this purpose, since the series of readings were then directly comparable without calculation. The figures recorded for [jx]D in Tables III and IV are in all cases for ilf/40 or ilf/10 solutions of the dry salt or dry base in water or 0T N acid, usually 01N sulphuric acid. Additive compounds of cinchona alkaloids with metallic salts. The elimination of the dihydro-bases from quinine and cinchonidine is easy, and from cinchonine and quinidine slow and laborious. In the hope of improving it numerous salts and derivatives were tried. Quinidine sulphate argentonitrate, B2. H2S04, AgNOs, proved useless, because it could not be recrystallised without decomposition. The zincichlorides of the type B.(HC1)2, ZnCl2, can be recrystallised, are easily purified, and the alkaloids are readily recoverable from them, but they are formed with equal facility and are of similar solubility with both the parent and the reduced bases and are therefore of no value as a means of separation. When this work was almost completed, a paper was published [Cohen, 1933] describing the specific precipitation by cupric chloride of cinchona alkaloids con¬ taining the vinyl group, and making the statement that ‘:no complex salts are precipitated when the corresponding dihydro-bases are treated with cupric chloride under exactly the same conditions, even after several weeks at — 4°.” As the cuprichlorides are represented by the formula B. (HC1)2, CuCl2, which is strictly analogous with that found for the zincichlorides, it seemed curious that this specificity should be exhibited by cupric chloride and not by zinc chloride. The behaviour of cupric chloride with commercial cinchonine and commercial quinidine was investigated carefully and it was found that the cuprichlorides did, in fact, effect a partial separation of the dihydro-bases. The resulting fractionation showed clearly that the dihydro-bases must form in¬ soluble cuprichlorides and, on trying the experiment, no difficulty was ex¬ perienced in preparing cuprichlorides of all four dihydro-bases, except in the case of dihydrocinchonidine, where the additive compound is readily soluble in cone. HC1 at atmospheric temperatures and when prepared in small quantities is best manipulated in a cold room. In the following account, the melting-points quoted are corrected; the combustion results are for material dried at 120° in vacuo unless otherwise stated and were obtained by micro-analysis. Quinine. The material used consisted of base prepared from commercial quinine sulphate. It had [a]/,’ -280-7° (c= J//40 in Nj 10 H2S04) and hydrogen absorption 94-7 %. It is known that cinchonidine can be eliminated from quinine by repeated crystallisation of the acid sulphate [Tutin, 1909]. The authors have found that quinine purified in this way is also free from dihydro, quinine, as indicated by its absorptive capacity for hydrogen. Purification can also be effected by crystallisation of the dihydrobromide [Emde, 1932]. The quinine acid sulphate was prepared by repeated crystallisation (five or six times is usually necessary) from hot water (1 in 7 to 8) until the rotation became constant. It was then recrystallised in three fractions, for which [a]/,’ showed the narrow range -216-1° to -217-0° (c = J//40 in water); the hydrogen absorption, for which the middle fraction was used, was 100-1 %. The dihydrobromide was prepared by recrystallisation from hot (43°) water (1 in 3 to 4) with the same precautions as the acid sulphate: the range of specific rotation for the three final fractions was - 189° to - 189C- and°, the hydrogen