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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    absorptions of the middle fractions were 100-8,101-5 and 101-6% (hydrogen absorptions by quinine dihydrobromide were generally high). The neutral hydrochloride and sulphate, made by neutralising pure quinine base with the appropriate acid, were recrystallised from hot water containing a trace of the appropriate acid to avoid any risk of inclusion of free base, which accounts for the high rotation shown by some specimens of neutral quinine salts. Constants for the pure base and salts are given in Table III. Dihydroquinine. The base, prepared by hydrogenation of pure quinine was crystallised from hot benzene, or as the neutral sulphate or the dihydrobromide from hot water. Constants for these three preparations are given in Table III. Dihydroquinine cuprichloride. Dihydroquinine (5 g.) was dissolved in cone. HC1 (8 ml.) and cupric chloride (5 g.) in cone. HC1 (8 ml.) added: the mixture was kept at 7° for 24 hours, but nothing separated. The side of the beaker just under the surface of the liquid was then rubbed vigorously with a glass rod for 5 minutes. A yellow streak appeared and in 20 minutes the liquid had set to a semi-solid, crystalline magma. The crystals were filtered out on Whatman filter-paper No. 54, washed sparingly with cone. HC1 and dried in a vacuous desiccator over soda lime; wt. 7-0 g. The product was recrystallised from 14 ml. hot cone. HC1; wt. 3-9 g. It crystallised on the sides of the container in silky, cushion-like masses of golden-brown needles, m.p. 204° (decomp.). (Found: C, 44-61; H, 5-22; N, 5-26; Cl, 26-60; Cu, 11-68%. C20H26O2N2.2HC1, CuCl2 requires: C, 44-98; H, 5-28; N, 5-25; Cl, 26-57; Cu, 11-9 %.) Dihydroquinine zincichloride. C20H2GO2N2.2HC1, ZnCl2. The base (5 g.) dissolved in cone. HC1 (8 ml.) was mixed with zinc chloride (12-5 ml. of 40 % solution in cone. HC1). Crystallisation began almost immediately, and the product was isolated in the same way as the cuprichloride. Yield 6-9 g. It crystallises from hot water (1 in 5) but shows a tendency to separate as an oil, which can be corrected by the addition of a little alcohol ; also from hot 50 % alcohol or from hot cone. HC1 in masses of colourless, flattened prisms, m.p. 257°; froths 262°. (Found: C, 45-12; H, 5-43; N, 5-28; Cl, 26-35; Zn, 12-20 %. Calc.: C, 44-82; H, 5-27; N, 5-23; Cl, 26-48; Zn, 12-22 %.) Quinidine. The quinidine base used had [a]))1 +324-3° (c = M[40 in A/10 H2S04) and hydrogen absorption 77-9 % indicating the presence of 22-1 % of reduced bases, chiefly dihydroquinidine. After recrystallisation from boiling alcohol, the first fraction (about 10 %) being rejected, it had [a% +325-5° and hydrogen absorption 76-4 %; these slight changes are accounted for by removal of cinchonine. The hydrogen absorption could not be raised by crystallisation of either the base from alcohol, or the dihydrobromide from water, but the dihydrochloride (1 in 1 in hot water) proved suitable for this purpose, the less soluble fractions being richest in quinidine, as indicated by increasing rotation and hydrogen absorption. Three such crystallisations give a yield of about 33 % by weight of the starting material, and raise the hydrogen absorption to 90 %. This pro¬ cedure answers well until a product having hydrogen absorption 98-0 to 98-5 % is reached. At this stage crystallisation from weaker solutions (1 in 3) ensures more rapid purification. At the first point at which approximate purity is reached, the yields are about 2-75 % of material with hydrogen absorption 100-6 % and about 7-5 % showing hydrogen absorption from 98 to 99 %. In the course of attempts to find a derivative of quinidine, which would expedite the tedious fractional crystallisation necessary especially in the last stages of purification by means of the dihydrochloride, addition compounds of the alkaloid with silver nitrate and with zinc chloride were examined. Quinidine argentonitrates. Two silver nitrate addition products of quinidine are known, one represented by the formula (C20H24O2N2)2, AgN03 [Stenhouse, 1864], which cannot be recrystallised without decomposition, and a second, obtained as a crystalline precipitate when silver nitrate is added to dilute solutions of quinidine sulphate. Though used as a test for quinidine, the origin of this latter reaction has not been traced, and the nature of the precipitate appears to be unknown. It was prepared by adding silver nitrate solution (5 ml. of 50 %) to a boiling, aqueous, faintly acid solution of quinidine sulphate (5 g.). As the solution cooled, colourless needles of quinidine sulphate argentonitrate separated. Yield 6-2 g. The substance is sparingly soluble in boiling water, but can be crystallised with some decomposition from boiling 50 % alcohol in colourless needles containing 2H20. Loss at 120° in vacuo 3-9: calc. 3-7 %.) m.p. 213° (decomp.). (Found: C, 51-3; H, 5-98; N, 7-72; MeO, 6-32; Ag, 11-74; S, 3-51 %. (C20H24O2N2)2.H2S04, AgN03 requires: C, 52-3; H, 5-4; N, 7-6; MeO, 6-7; Ag, 11-7; S, 3-49 %.) The carbon determinations were per-