The constitution of hydroxysulphapyridine and synthesis of 2-aminohydroxypyridines.

Hydroxysulphapyridine was isolated as a metabolite of sulphapyridine in the dog by Scudi (1940, 1944) and by Weber, Lalich & Major (1943). In an investigation of the metabolism ofsulphapyridine in the rabbit, we obtained a compound which appeared to be identical with the hydroxysulphapyridine produced by the dog (Bray, Neale & Thorpe, 1946). The constitution was not determined, but evidence was obtained that one hydroxyl group had been introduced. Scudi (1944) had suggested that this occupied either position 3 in the pyridine ring or position 2 in the benzene ring. Since, however, hydrolysis of hydroxysulphapyridine gave sulphanilic acid and a compound believed to be an aminohydroxypyridine it was more reasonable to infer that the hydroxyl was attached to the pyridine ring (Weber et al. 1943; Bray et al. 1946). In the expectation that hydroxylation might occur in position 5, we synthesized a compound which the literature led us to believe was 2-amino-5-hydroxypyridine. Since this compound was different from that obtained from the rabbit we attempted to synthesize the other three isomers. This investigation revealed that the so-called '2:5 '-compound was really the 2:3-isomer. Of the four possible isomers two, 2-amino-3-hydroxypyridine and 2-amino-6hydroxypyridine, have been obtained by routes which leave little doubt of their configuration. We have not succeeded inpreparing 2-amino-5-hydroxypyridine, althoughwe have obtained strong evidence that it does indeed form the aminohydroxypyridine moiety of hydroxysulphapyridine. Since we met with considerable difficulty in the preparation of aminohydroxypyridines and found some discrepancies in the literature, we include in this report a brief summnary of some of the syntheses carried out.