Modified cinchona alkaloids. Pt. 1, Apoquinine and apoquinidine / by T.A. Henry and W. Solomon.

  • Thomas Anderson Henry
Date:
[1934]
Catalogue details

Licence: Public Domain Mark

Credit: Modified cinchona alkaloids. Pt. 1, Apoquinine and apoquinidine / by T.A. Henry and W. Solomon. Source: Wellcome Collection.

    8/12 page 1928
    in m. p. are no doubt mainly due to differences in purity of materials, but may also in part be due to the fact that pure apoquinine froths at 184° and, on continued heating the froth becomes transparent at about 205°, and observers may record either or both of these points. Apoquinine crystals lose nothing when dried at 120° in a vacuum, but the finely powdered base loses 7% by weight after 8 hours at 110—135° (Found : C, 73-4; H, 7-6; N, 8-9. Calc, for C19H2202N2 : C, 73-5; H, 7-2; N, 9-0%). The hydrochloride forms clusters of colourless needles, m. p. 272-5°, [a]1^0 — 163-8°. Aqueous solutions are pale yellow : the colour is intensified by heat and is discharged by addition of acid. Solutions in alcohol are colourless. The salt is sparingly soluble in alcohol or water, but readily soluble in mixtures of the two solvents. It is anhydrous (Found : C, 65-8; H, 6-7; N, 8-2; Cl, 10-2. Calc, for C19H2202N2,HC1 : C, 65-75; H, 6-7; N, 8-1; Cl, 10-2%). The dihydro chloride crystallises from dry alcohol in colourless spherical nodules, m. p. 261°, MiT — 224-4°. It loses 8-7% by weight in a vacuum at 110°, is hygroscopic, and appears to be readily dissociated, all the samples examined being slightly deficient in chlorine (Found : Cl, 17-7. C19H2202N2,2HC1 requires Cl, 18-5%). The hydrobromide forms colourless needles, m. p. 284°, from dilute alcohol (Found : Br, 20-7. C19H 220 2N2,2HBr requires Br, 20-4%). The dihydrobromide crystallises from dry alcohol in colourless or faintly yellowish-grey spangles, m. p. 255°, [a]^° — 180-9°, and, like the dihydrochloride, seems to dissociate, being always slightly deficient in bromine (Found: C, 48-05; H, 5-5; N, 5-8; Br, 32-1 to 33-2. Ci9H2202N2,2HBr requires C, 48-3; H, 5-1; N, 5-9; Br, 33-9%). The acid sulphate crystallises in two forms : (a) from methyl alcohol in thin, soft, lemon- yellow platelets, and (6) stout, hard, almost colourless, thin, hexagonal plates from water. The two forms lose 10-7 and 8-0% by weight respectively on drying and re-absorb these amounts on exposure to air. The salt is sparingly soluble in water (2% approx.) or methyl alcohol. The (a) form sinters at 90° when rapidly heated, and at 170—190° when heated slowly, then darkens and finally froths at 200°. The (b) form melts sharply at 203° to 208° depending on the rate of heating, [a]9° — 223° (Found : C, 55-7; H, 6-0; N, 6-9; S, 7-7. C19H2202N2,H2S04 requires C, 55-8; H, 5-9; N, 6-9; S, 7-85%). The sesquioxalate crystallises from alcohol in pale yellow needles, is sparingly soluble in water or alcohol, has m. p. 224-5—226°, [a]9° — 193-6° (c — 0-212 in water) [Found : C, 59-55; FI, 5-8; N, 6-3. Calc, for (C19H2202N2)2,3H2C204 : C, 59-3; H, 5-7; N, 6-3%]. Suszko {Bull. Inter. Acad. Polonaise, 1925, 143) gives m. p. 228°, [a]D — 168—170° {c = 0-84 in water) to a sesquioxalate of “ apoquinine ” prepared from either quinine or (3-isoquinine by Hesse’s method {loc. cit.). The acid dianisoyl-d-tartrate prepared for comparison with the chlorine-free component of Oberlin’s “ apoquinine ” (p. 1926) is a colourless crystalline powder, has m. p. 235-5°, and is anhydrous (Found: C, 64-3; H, 5-7; N, 4-0; MeO, 8-8. C19H22O2N2,C20H18O10 requires C, 64-3; H, 5-5; N, 3-85; MeO, 8-5%). Apoquinine methyl ether was obtained in poor yield by the action of diazomethane on the base, and after treatment with sodium hydroxide solution to remove unchanged phenolic base, was converted into hydrochloride, which was recrystallised from dry alcohol, by addition of acetone and a little ether. The salt separated in hemispherical aggregates of colourless needles, m. p. 249—251°, [a]^° — 196°, was readily soluble in water or alcohol but sparingly in acetone, and was anhydrous (Found: C, 66-5; H, 7-0; N, 7-6; Cl, 9-8. C20H24O2N2,HCl requires C, 66-5; H, 7-0; N, 7-8; Cl, 9-8%). The base regenerated from the hydrochloride crystallised from benzene in anhydrous, colourless, aggregates of needles, m. p. 183—185° after sintering at 180° {no decomp.), [a]^° — 201-2° {c = 0-811 in alcohol). Miura {loc. cit.) gives m. p. 175—176°, [a]9° — 201*5°, and Suszko et al. {loc. cit.), m. p. 186—187°, [a]D — 192° {c = 1 in alcohol). Apoquinine ethyl ether, prepared by the use of ethyl sulphate, gave a hydrochloride, which crystallised from hot acetone (1 g. in 10 c.c.) in anhydrous, short, colourless needles, m. p. 247—250°, [a]9° — 191-7° (Found: C, 67-6; H, 7-45; N, 7-45; Cl, 9-45. C21H2602N2,HC1 requires C, 67-2; H, 7-3; N, 7-5; Cl, 9-5%). The base regenerated from this and crystallised from benzene had m. p. 195—197°, after sintering at 189° {no decomp.) and [a]^f — 199-7° {c — 0-846 in alcohol). Previous figures for the ethyl ether are : m. p. 195—196°, [a]^° — 174-7° (Miura, loc. cit.); m. p. 182° (Lippmann and Fleissner, loc. cit.); m. p. 183° (Giemsa and Bonath, Ber., 1925, 58, 95). Action of Sulphuric Acid (60%) on Quinidine.—-The quinidine used was purified through the cuprichloride and dihydrochloride as already described (Buttle, Henry, and Trevan, loc. cit.) and was 99-5% pure, as estimated by absorption of hydrogen in presence of colloidal palladium. It was converted into crude apoquinidine by the method described under apoquinine (p. 1927), the recovery of undemethylated base being 15-0% and the yield of crude apoquinidine 77-0%.
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