The synthesis of glyoxaline derivaties allied to pilocarpine / by Frank Lee Pyman.

  • Pyman, Frank Lee.
Date:
[between 1910 and 1919?]
Catalogue details

Licence: In copyright

Credit: The synthesis of glyoxaline derivaties allied to pilocarpine / by Frank Lee Pyman. Source: Wellcome Collection.

    5/16 (page 534)
    apparently the same mixture of the two a-4(or 5)-glyoxalinemethyl- fi-ethylsuccinic acids (IX) is formed, for in each case the product gradually deposited only a small amount of the same crystalline acid, melting at 236° (corr.), the bulk remaining amorphous. On ChEL-CH-‘C H •CHo'ONII 2 5 | | 2 , | >CH CO,H CO,H CH-N (IX.) the supposition that an equilibrium mixture of the two acids had been obtained, the amorphous acids were on one occasion again subjected to treatment with concentrated hydrochloric acid, but no mere of the crystalline acid could be isolated from the product. The remaining amorphous acids were then esterified, and an attempt made to separate the resulting ethyl a-4(or 5)-glyoxaline- methyl-/3-ethylsuccinates by crystallisation of the hydrogen oxalates, but although crystalline salts were obtained, no satisfactory separa¬ tion took place. On esterifying the pure, crystalline «-4(or 5)-glyoxalinemethyl- /3-ethylsuccinic acid melting at 236° (corr.) with absolute alcohol and hydrogen chloride, ethyl a-4(or b)-glyoxalinemethyl-fi-ethylswc- cinate (X) was obtained. It was isolated in the form of its beauti¬ fully crystalline hydrogen oxalate, and in view of the similarity of its structure to that of pilocarpine (XI) was submitted to physio¬ logical examination; it proved to be practically inactive : C9H,-CH CH-CH2-C-NH\r)tT 2 5 l i 2 11 ^MJH C02Et C02Et CH*N CotL’CIL—CH*CH0*C*NMe CO CEE 11 CH-N :>ch o (X.) (XI.) It may perhaps be mentioned at this point that had the isomeric a-4(or 5)-glyoxalinemethyl-j8-ethylsuccinic acids been obtainable in good yield, the preparation of their anhydrides, the reduction of these to the corresponding lactones, followed by methylation/ and resolution of the products were to have been carried out with the object of synthesising pilocarpine. Owing, however, to the poor yields of the acids, these experiments were discontinued, for each of the (2) corresponding anhydrides might yield two isomeric lactones (A and B) on reduction, and each of the (4) lactones would EfCR—CR-CHg-CgHgNg CH2 CO Et-CH—CR-CH2-C3H3N2 CO CHo o o (A.) (B.) yield on meth^iation two isomeric (1 :4- and 1 :5-) A-methyl deriv¬ atives, thus giving rise in all to eight optically inactive (externally