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.

    7/12 page 1927
    Action of Sulphuric Acid (60%) on Quinine.—Commercial quinine contains cinchonidine and dihydroquinine, from which it is easily purified by recrystallisation of the acid sulphate (Buttle, Henry, and Trevan, loc. cit.). For that reason quinine acid sulphate was employed as a starting material. The process used was that described by Suszko et al. [loc. cit.) with the exception that the alkaline solution of the crude phenolic base was shaken out with ether to remove any remaining undemethylated base (1-3—8%). The latter does not appear to be quinine and is still under investigation. The yield of crude apoquinine is difficult to state, since the moisture content after drying in a vacuous desiccator varied considerably, but is probably about 80% of the theoretical. The carbonated liquors left after the precipitation of apoquinine, still contain alkaloid, which can be recovered by long-continued treatment with ether (about 100 hours) in a continuous-extraction apparatus. The product, which does not appear to be apoquinine, is being accumulated for examination (yield, 6%). The crude apoquinine is dissolved in hot acetone (1 g. in 25 c.c.), the solution filtered to remove inorganic material, concentrated to low bulk, diluted with sufficient alcohol to form a clear solution, and neutralised with iV-hydrochloric acid. Water is then added, and the bulk of the organic solvents removed by distillation in a vacuum. The neutral hydrochloride crystallises as the solution cools, and a second crop is obtained by evaporating the mother- liquor to dryness in a vacuum and boiling the residue with dry alcohol. The whole of the crude hydrochloride is boiled with dry alcohol (1 g. in 5 c.c.) to remove coloured impurities and finally recrystallised by solution in 50% alcohol (1 g. in 10 c.c.) and removal of about half the solvent by distillation in a vacuum. It then has m. p. 265°, [a]^° — 154-5° (c — 0-9 in water) (Found : C, 64-8; H, 6-7; N, 7-9; Cl, 9-9; OMe, nil. C19H2202N2,HC1 requires C, 65-75; H, 6-7; N, 8-1; Cl, 10-2%). No matter what method of purification was adopted this deficiency of 1% in carbon could not be overcome. Suszko et al. (loc. cit.) give for their hydrochloride prepared from crude apoquinine and repeatedly recrystallised, m. p. 236—237°, [a]D — 145° (c = 1 in water) and Cl, 10-08% and provide no further analytical data. Though the hydro¬ chloride so obtained is impure, its preparation is necessary as a preliminary means of purification. The base is then recovered from it and converted into the acid sulphate by solution in methyl alcohol and addition of the calculated quantity of iV-sulphuric acid. The residue left on evaporation of the solution in a vacuum is redissolved several times in methyl alcohol and taken to dryness each time, to remove as much water as possible, and is finally dissolved in hot methyl alcohol (1 g. in 20 c.c.), from which it crystallises on cooling. Further crops are obtained with difficulty on concentration of the mother-liquor. The whole of the crops are recrystallised from methyl alcohol and then yield pure apoquinine acid sulphate. Six fractions of such material, obtained by the recrystallisation of 10 g. from water, had [a]^° ranging only from 221-25° to 223-25°. Apoquinine base is prepared by pouring a saturated aqueous solution (2% approx.) of this salt into excess of a saturated aqueous solution of sodium carbonate in presence of ether (100 c.c. per g. of base) and shaking vigorously until all the alkaloid has been extracted, more ether being used if necessary. The ethereal solution is dried for a short time only (to avoid crystallisation of the base at this stage) over anhydrous sodium sulphate, and the solvent re¬ moved by slow distillation. As concentration proceeds, apoquinine crystallises in a pure condition. The combined methyl-alcoholic mother-liquors, which have ceased to deposit apoquinine acid sulphate, are taken to dryness in a vacuum, and the residue dissolved in hot water. This solution deposits an acid sulphate, closely resembling apoquinine acid sulphate, but having a higher specific rotation, [a]^J — 235°, which, so far, it has not been found possible to alter by fractional crystallisation. The base recovered from this salt crystallises well and is also mainly distinguished from apoquinine by its higher specific rotation. It may be one of the numerous possible stereoisomerides of apoquinine and is still under examination. Apoquinine crystallises in small, colourless, transparent, triangular prisms, is readily soluble in ethyl or methyl alcohol and sparingly soluble in ether or acetone. It froths at 184° and has MlT — 281° (c = 0-784 in N/10-sulphuric acid), or — 214-8° (c — 0-775 in alcohol). Crystals of apoquinine have been obtained, apparently with difficulty, twice previously. Lippmann and Fleissner (loc. cit.) record m. p. 210° with shrinkage at 160°, [<*% — 217° (c — 0-7877 in alcohol), whilst Frankel and Buhlea (loc. cit.) give m. p. 160° and [a]D — 196-37° (c = 0-7995 in alcohol). No more recent author appears to have succeeded in crystallising apoquinine. Miura (Japan J. Med. Sci., 1930, 5, 1) states that amorphous apoquinine, prepared by a new method, not yet described, sinters at 170°, melts at 210°, and has [a]™0 — 216-1°, and Suszko et al. (loc. cit.), for their amorphous base, give m. p. 190—195° and [a]^° — 188-7—191-7° (c = 1 in water). The crystalline base described above does not dissolve appreciably in water. These discrepancies
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