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.

    5/12 page 1925
    The comparable data available are scanty, but so far as they go they indicate a close re¬ semblance between the constants of the supposed cupreidine with those of dihydrocupreidine, whilst the characters of the methyl ether of the supposed cupreidine agree much better with those of dihydroquinidine, the methyl ether of dihydrocupreidine, than with those of quinidine. It is not well known that the well-crystallised and apparently pure quinidine of commerce usually contains about 20% and may contain as much as 30% of dihydroquinidine (Buttle, Henry, and Trevan, Biochem. J., 1934, 28, 434). On demethylation, commercial quinidine yields a product containing much dihydrocupreidine, and this, on re-methylation, will yield dihydroquinidine, and it seems possible that the substance described by Suszko and his collaborators as cupreidine may be in reality largely dihydrocupreidine, and its methyl ether, not quinidine, but dihydroquinidine. The present authors have repeated the work of the Polish investigators, using as a starting material quinidine purified by a method already described (Buttle, Henry, and Trevan, loc. cit.) and of 99‘5% purity as measured by its capacity for hydrogen absorption. This, on demethylation by boiling 60% sulphuric acid, yields two products, neither of which has been described previously. The first, C19H2202N2, it is proposed to call isoapoquinidine, because it is laevorotatory, and probably represents a greater change in the quinidine molecule than the second substance, which is dextrorotatory; further, all the “ apoquinidine ” hitherto obtained has been amorphous and markedly dextrorotatory and it seems desirable to reserve the name apoquinidine for the second and dextrorotatory product of this reaction. i so Apoquinidine differs markedly from “ cupreidine/' having m. p. 245° and [a]“’ —12*6° (c = 1 in alcohol) : its neutral salts are also laevorotatory, but the acid salts are dex¬ trorotatory. The second product, apoquinidine, is crystalline, yields well-crystallised salts and is dextrorotatory, but it is not yet possible to say whether it has been freed entirely from fsoapoquinidine. As by-products of the action of 60% sulphuric acid on quinine and quinidine, two non- phenolic bases have been obtained in small quantity; these are still under investigation and appear to be isomerides of the two starting materials. In the preparation of crude apoquinine, by precipitation with carbon dioxide from solution in aqueous sodium hydroxide, some alkaloid remains in solution, and can be recovered by long-continued extraction of the alkaline liquor with hot ether. This product is being accumulated for examination. No analogous product is found at the corresponding stage in the preparation of crude apoquinidine. Experimental. In the following account the m. p.’s are corrected and, unless otherwise stated, are also decomposition points; they are of little diagnostic value, as they vary with the rate of heating. The specific rotations are recorded for the dry substance and, unless stated otherwise, the solutions are Tf/40 and the solvent is water for the salts and A/’/10-sulphuric acid for the bases. Except in one case (p. 1926) the combustion results are recorded for the substance dried in a vacuum at an appropriate temperature, usually 120°. With the exception of fsoapoquinidine, none of the phenolic bases dry to constant weight, but ultimately reach a stage at which there is a constant minute loss. In these cases the substance has been taken as anhydrous at the point at which the drying curve begins to flatten. Many cinchona alkaloidal salts are either efflorescent or hygroscopic and consequently show great variation in loss of weight on drying. For that reason, the losses found are not usually represented by a definite number of molecules of water or other solvent, unless special precautions are taken. The authors have, therefore, merely recorded the percentage loss found in the particular preparation used for analysis. It was quite frequently different in other preparations of the same substance. Action of Aluminium Chloride on Quinine.—Crude “ apoquinine, prepared and isolated by Oberlin’s method [loc. cit.), is a pale yellow or cream-coloured powder (yield, 70%), appreciably soluble in water, sparingly soluble in benzene or ether, more so in acetone, and readily in chloroform or alcohol; m. p. 175°, [a]^ — 177° (c = 0-514 in methyl alcohol) (Found : Cl,
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