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.

    4/12 (page 1924)
    drastic, and present considerable possibilities of racemisation, and that the addition of the elements of hydrogen chloride to the unsaturated side chain of apoquinine may give rise to isomerides. For these reasons, complete identity, e.g., in specific rotation, in products prepared in different ways is hardly to be expected. Now that pure apoquinine is readily obtainable, it will be possible to investigate these points of detail and for the present it is merely intended to settle the question of the composition of “ apoquinine ” prepared by the aluminium chloride process. Demethylation by boiling with 60% sulphuric acid has been applied to quinine by Jarzynski, Ludwiczakowna, and Suszko (Rec. trav. chim., 1933, 52, 839) and to quinidine by Ludwiczakowna, Suszko, and Zwierzchowski (ibid., p. 847). In the case of quinine the Polish authors obtained apoquinine, which they were unable to crystallise, but from which they succeeded in preparing a number of crystalline derivatives, including a neutral hydrochloride, m. p. 236—237°, [a%°° — 145° (c = 1 in water). The only analytical figure given is for chlorine, 10*08 (calc., 10*23%). Although the present authors believe Suszko and his co-workers to be mistaken in the view that this amorphous “ apoquinine ” is a pure sub¬ stance, it should be recorded that this product is a great improvement on most of the “ apoquinines ” previously described, and is a material from which, as shown below, it is possible to prepare pure crystalline apoquinine in any desired quantity. On repeating this work the authors always obtained a crystalline hydrochloride, m. p. 265°, [a]^00 — 154*5° (c = 0*9 in water), and this on complete analysis invariably gave results nearly 1% low in carbon. They, therefore, had recourse to other salts and it was found that the best salt for purification is the acid sulphate, which crystallises well, gives satisfactory analytical results, and from which, for the first time, apoquinine base has been obtained easily and in quantity in well-defined crystals. From it a series of well-crystallised salts, including the pure neutral hydrochloride, m. p. 272*5°, [a%°° — 163*8°, has been prepared. The base regenerated from the crude crystalline hydrochloride first obtained, yields two acid sulphates, the one referred to above having [0%°° — 223*0° and a second having [«]J° — 235°. This second salt is still under investigation, but sufficient data have been obtained to indicate that it may be the acid sulphate of an isomeride of apoquinine. In spite of the hitherto ill-defined character of apoquinine a constitutional formula has been proposed for the alkaloid by Suszko et al. (loc. cit.; Bull. Inter. Acad. Polonaise, 1925, 129) which may be written in linear form as follows : MeO‘C9H5N*CH(OH)*C7H11N*CH:CH2 —> HO-C9H5N*CH(OH)*C7H10N:CH-CH3 Quinine Apoquinine As apoquinine has now been obtained in a satisfactory condition for investigation, and as it seems possible that at least two species are already obtainable, the authors propose to reserve any comments regarding this and other possible formulas until they have accumulated a broader basis of experimental data. Though apoquinidine has received less attention than apoquinine, there has hitherto been no reason to suppose that quinidine differs from quinine by undergoing simple demethylation, without further intramolecular change. The observation of Suszko and his collaborators (loc. cit.) that quinidine, on demethylation with boiling 60% sulphuric acid, yields the hitherto unknown cupreidine, a dextro-isomeride of cupreine, was therefore surprising. The chief item of evidence upon which this view is based is that cupreidine on simple methylation regenerates quinidine, just as its analogue, cupreine, on similar treat¬ ment yields quinine. For convenience of comparison the m. p/s and specific rotations of cupreidine, dihydrocupreidine, quinidine, dihydroquinidine, and the methyl ether of cupreidine have been assembled in the following table. Dihydro- Cupreidine Cupreidine. Dihydrocupreidine. Quinidine. quinidine. methyl ether. Base. B,HC1. Base. B,HC1. Base. Base. Base. M. p. 186—190° 215—216° 185—195° 230—232° 173*5° 169*5° 169*0° Sp. rot. +219*4° +190° +227*2° +194*0° +266*1° +230*8° +234*1° (c= 1*116; (c = 1; (c = 1*116; (c = 0*872; [c = 1; (c = 1; (c = 0*994 EtOH) H20) EtOH) HaO) EtOH) EtOH) EtOH)