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.

    11/22 (page 435)
    sistently low in recrystallised specimens, owing to the slight decomposition observed on re- crystallisation, but there can be little doubt that the substance is correctly represented by the formula given. The “quinidine” recovered from the silver nitrate compound absorbed 8T1 % of the calculated amount of hydrogen, which is only a slight improvement on the original figure of 78%. Quinidine zincicMoride. This was made by the usual method (p. 434) using quinidine 1 in 5 and zinc chloride 1 in 3 of cone. HC1. It crystallises from hot water or 50 % alcohol but best from hot cone. HC1 (1 in 3) when it forms much-twinned colourless prisms, m.p. 242° (decomp.). In the following analyses the two figures for each constituent are for material crystallised from cone. HC1 and water respectively and dried at 120° in vacuo. (Found: C, 44-98, 45-0; H, 5-13, 5-10; N, 5-32, 5-49; MeO, 6-02, 6-23; Cl, 25-9, 25-48; Zn, 12-5, 12-4 %. C20H24O2N2.2HC1, ZnCl2requires: C, 44-9; H, 4-87; N, 5-25; MeO, 5-8; Cl, 26-5; Zn, 12*2 %.) This is the formula adopted by Stenhouse for what was undoubtedly the same substance and the foregoing confirms and extends his description. Quinidine cuprichloride. In view of the claim [Cohen, 1933] that the vinyl-containing cinchona alkaloids form solid cuprichlorides whilst the dihydro-bases do not, this method was tried on quinidine. The “quinidine” was not recovered by Cohen’s method of removing copper as the sulphide but by the simpler process of dissolving and thereby decomposing the cuprichloride in cold water and pouring the filtered solution into excess of ammonia solution, when the base is precipitated and is readily filtered and washed free from the ammoniacal copper solution. The following is a typical result of a close imitation on a larger scale of one of Cohen’s experiments with the modification just referred to, starting with a “quinidine” fraction having a hydrogen absorption of 51-6 %: Cohen used a mixture, quinidine-dihydroquinidine (1:1). The “quinidine” (11 g.) was dissolved in cone. HC1 (40 ml.) and cupric chloride (11 g.) in 36 ml. hot cone. HC1 added. On cooling, the orange-coloured crystalline cuprichloride separated and was collected, dried overnight on a porous tile and finally in a vacuous desiccator over soda lime for 48 hours. Yield 11 g. A filtered aqueous solution of the cuprichloride (3 g. in water 30 ml.) was run into solution of ammonia (10 ml. cone. NH4OH with water 30 ml.) and the pre¬ cipitated base collected, thoroughly washed and dried in a vacuous desiccator. Yield 1-97 g. It absorbed 67-5 % of the calculated amount of hydrogen, i.e. an improvement of 15-9 %. In other trials with varying amounts of hydrochloric acid as solvent such results as the following were obtained; the figures are the hydrogen absorption values % of (a) the “quinidine” used, and (6) the recovered “quinidine.” (a) 77*9 77-9 86-6 78-6 80-4 88-1 95-8 (b) 91-0 88-0 88-7 80-4 88-1 95-8 98-0 The method has obvious possibilities and by combining it with the present authors’ method— recrystallisation of the dihvdrochloride—it is possible to obtain the latter in a pure state. 1 he remainder of the “quinidine cuprichloride (8 g.) prepared from the 51-6 % “quinidine' referred to above, was recrystallised from hot cone. HC1 (1 g. in 3 ml.) and the whole of the crop (4-6 g.) ground in a mortar with water (9 ml.). Under these conditions the cuprichloride decomposed, and part of the quinidine dihydrochloride formed crystallised out. This was collected and without washing or drying was converted into base as already described. Yield 2-15 g. This absorbed 85-2 % of the calculated amount of hydrogen, an improvement of nearly 34 %. Still better quinidine but in poorer yield can be obtained by the use of more water (3 or 4 ml. instead of 2 ml. for 1 g. of cuprichloride). The base recovered from the dihydrochloride mother-liquors is of poorer quality. Starting with “quinidine” showing hydrogen absorption 77-9 % and using cone. HC1 (5 ml.) for each g. of quinidine or cupric chloride employed, it is possible by one treatment by this modified process, to obtain 1/3 of the original amount as a fraction showing hydrogen absorption about 95-4 % and by repeating the operation to obtain about 1/9 of the original amount having hydrogen absorption 99 to 100 %. The quinidine used in determining the constants of the base, acid sulphate and dihydrobromide recorded in Table III was made by both processes. No figures are given for quinidine dihvdro- chloride as this substance is not completely dehydrated at 120° in vacuo, and between 120° and 130° the loss is irregular owing to incipient decomposition.