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

  • Henry, Thomas Anderson, 1873-1958.
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.

    6/12 (page 1926)
    5-3; MeO, 0-5. Calc, for the equimolecular mixture C19H2202N2 -f- C19H2302N2C1 : Cl, 5-4%). Oberlin (loc. cit.) found no chlorine and Jarzynski, Ludwiczakowna., and Suszko (loc. cit.) confirm this by stating that “ apoquinine ” prepared by this method is the same as that made by the sulphuric acid process (p. 1927). As a similar discrepancy is recorded for Hesse’s “ apoquinine,” obtained by the action of hydrochloric acid (d 1-125) at 140° on quinine (Hesse, loc. cit.; Ber., 1895, 28, 1301; Lippmann and Fleissner, Monatsh., 1895, 16, 34; Lippmann, Ber., 1895, 28, 1971; Frankel and Buhlea, Ber., 1925, 58, 559), a specimen of this material was prepared; it closely resembled Oberlin’s product but contained less chlorine (2-6%). This equimolecular proportion of apoquinine and chlorodihydroapoquinine is preserved through several salts. When the crude product (1 g.) is dissolved in hot concentrated hydro¬ chloric acid (2 c.c.), the solution, on cooling, deposits slender colourless needles. This substance, on recrystallisation in like manner till colourless, has m. p. 225° (dry), [a]o° — 204-1° (Found : C, 56-3; H, 6-3; N, 6-5; Cl, 22-5. C19H2202N2,2HC1 + C19H2302N2C1,2HC1 requires C, 56-8; H, 6-15; N, 7-0; Cl, 22-1%). Similarly, when crude “ apoquinine ” (1 g.) in hot hydro¬ chloric acid (2 c.c.) is mixed with a solution of zinc chloride (1 g.) in the same solvent (2 c.c.), a mixture of zincichlorides crystallises on standing, and this on recrystallisation from hot hydro¬ chloric acid forms pale yellow needles, m. p. 242° [Found : C, 42-2; H, 4-8; N, 5-2; Cl (total), 29-5; Cl (non-ionisable), 3-15; Zn, 12-45. C19H2202N2,2HCl,ZnCl2 + C19H2302N2Cl,2HCl,ZnCl2 requires C, 42-4; H, 4-5; N, 5-2; Cl (total), 29-7; Cl (non-ionisable), 3-3; Zn, 12-2%]. This mixture, on repeated crystallisation from hot hydrochloric acid, becomes sticky and the m. p. falls. It cannot be crystallised from water or alcohol. Out of many methods tried, three ways have been found of isolating the two chief components of crude “ apoquinine ” and though none of these is of practical value, the yields being so poor, two of them are now described briefly, as the results confirm the view expressed above as to the composition of this mixture. When crude “ apoquinine ” is boiled with acetone (1 g. in 10 c.c.) it dissolves and almost immediately deposits a white powder (40%), which when air-dry has m. p. 175°. When dried at 105° in a vacuum, it loses 7-6% by weight after 11 hours, and at this stage contains Cl 7-0% and has [a]p° — 188-4° (c — 0-484 in methyl alcohol). It continues to lose weight on further drying, but gradually turns black. On solution in warm methyl alcohol (1 g. in 2 c.c.) and addition of acetone (2 c.c.) the product deposits clusters of prismatic crystals and, by repeated crystallisation in this manner, a 10% yield of a substance, m. p. 182—183°, [a]2D°° — 200-0° (c = 0-625, air-dry substance in methyl alcohol), is obtained. This behaves like the anterior product on drying, and was analysed in an air-dry condition, in which it appears to contain one molecule of acetone (Found: C, 65-7; H, 7-2; N, 7-2; Cl, 9-0. Ci9H2302N2C1,C3H60 requires C, 65-2; Id, 7-2; N, 6-9; Cl, 8-8%). The substance is, therefore, chlorodihydroapoquinine. A series of salts was prepared, of which the acid sulphate may be described : aggregates of transparent yellow plates, sinters at 192°, darkens at 195° and liquefies at 205°, [a]^0 — 206-7° (c = 0-556 in water), becomes anhydrous over sulphuric acid in a vacuous desiccator; loss 8-7—9-4% (Found: C, 51-2; H, 6-0; N, 6-4; Cl, 7-7; S, 7-2. Ci9H2302N2C1,H2S04 requires C, 51-3; H, 5-7; N, 6-3; Cl, 8-0; S, 7-2%). For comparison a specimen of chlorodihydroapoquinine was made by Zorn’s method (/. pr. Chem., 1871, 4, 44; 1873, 8, 279) and converted into the same series of salts. The only difference noted was that the base now described and its salts had higher specific rotations than the cor¬ responding Zorn base and its salts. The acid sulphate, for example, showed the same characters as those just described, but had [a]^° — 198-6° (c = 0-556 in water), a discrepancy for which an explanation has been suggested already (p. 1923). When hot solutions in alcohol of crude “ apoquinine ” and of excess of dianisoyl-d-tartaric acid (Rabe and Meyer, Annalen, 1932, 492, 265) are mixed, a white, crystalline powder separates as the mixture cools. This substance is insoluble in all ordinary solvents and can only be recrystallised by solution in boiling glacial acetic acid (1 g. in 10 c.c.), concentration of the solution in a vacuum to 2-5 c.c., and dilution with dry alcohol (12 c.c.). Each crystallisation reduces the quantity available by 50—75%, but the 5% of chlorine contained in the crude product is reduced in 2 or 3 crystallisations to 0-5%. The best specimen obtained consisted of minute colourless granules, m. p. 242° (Found: C, 63-9; H, 5-8; N, 4-3; Cl, 0-2; MeO, 9T. C19H22O2N2,C20H18O10 requires C, 64-3; H, 5-5; N, 3-85; Cl, nil; MeO, 8-5%). This only differs from pure apoquinine acid dianisoyltartrate (p. 1928) in containing 0-2% of chlorine, but the base recovered from it has m. p. 180° (no depression on admixture with pure apoquinine), and [oc]1^0 — 196-5° (c — 0-579 in methyl alcohol), whereas pure apoquinine froths at 184° and has [a]1^0 — 212° {c — 0-6585 in methyl alcohol), the reason for this discrepancy being no doubt that already stated (p. 1923).