Reactions of l-ascorbic and isoascorbic acids with hydrazines related to sulfanilamide drugs

Abstract

Various compounds related to the antibacterial, sulfanilamide drugs have been prepared from dehydro- l-ascorbic acid or its d- erythro analog by reaction with hydrazines related to sulfanilamide, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxydiazine, whereby the 2-mono- and 2,3-bis-(hydrazone) were isolated. After opening of the lactone ring in the bis(hydrazones) with alkali, nucleophilic attack, on the carbonyl group, of the imino nitrogen atom of the 3-hydrazone residue afforded 3-( l- threo-glycerol-1-yl)-1-phenyl- and -1-( p-sulfamylphenyl)-4,5-pyrazole-dione 4-( p-sulfamylphenlhydrazone) and the related 3-( d- erythro-glycerol-1-yl)compounds. Whereas acetylation of l- threo-2,3-hexodiulosono-1,4-lactone 2,3-bis( p-sulfamylphenylhydrazone) (9) and 3-( l- threo-glycerol-1-yl)-1-( p-sulfamylphenyl)-4,5-pyrazoledione 4-( p-sulfamylphenylhydrazone) ( 15) gave the O-acetyl derivatives, benzoylation of 15 gave the di- N-benzoy ltri- O-benzoyl compound. Reaction of 9 with cupric chloride gave 3,6-anhydro-3-( p-suIfamylphenylazo) - l-xylo-2-hexulosono-1,4-lactone 2-( p-sulfamylphenylhydrazone). The 3-( l-threo-glycerol-1-yl)-1-( p-sulfamylphenyl)flavazole ( 35) was prepared by the rearrangement of 3-[(1- p-sulfamylphenyl)hydrazono- l- threo-trihydroxybutyl]-2-quinoxalinont ( 33). Periodate oxidation of 15, 33, and 35 gave 3-formyl-1-( p-sulfamylphenyl)-4,5-pyrazoledione 4-( p-sulfamylphenylhydrazone), 3-1-[( p-sulfamylphenyl)hydrazono]glyoxal-1-yl]-2-quinoxalinone, and 3-formyl-1-( p-sulfamylphenyl)flavazole, respectively. The i.r. and n.m.r. spectral data for some of these derivatives are reported.