Syntheses of substituted 1-methyl-2-(1,3,4-thiadiazol-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles

Article abstract of DOI:10.1002/jhet.5570320121

Starting from readily available ethyl-4-nitropyrrole-2-carboxylate (1), substituted 1-methyl-2-(1,3,4-thiadiazel-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles were prepared. The reaction of 1 with diazemethane gave ethyl 1-methyl-4-nitropyrrole-2-carboxylate (2). Reaction of compound 2 with hydrazine hydrate afforded the corresponding hydrazide 3. The reaction of 3 with formic acid yielded 1-(1-methyl-4-nitropyrrole-2-carboxyl)-2-(formyl)hydrazine (7). Refluxing of the latter with phosphorus pentasulfide in xylene yielded compound 6 in 40% yield. Reaction of compound 7 with phosphorus pentoxide afforded compound 9. Reaction of compound 3 with 1,1'-carboxyldiimidazole in the presence of triethylamine yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-oxadiazoline-4(H)-5-one (11). Refluxing compound 3 with cyanogen bromide in methanol gave compound 12. Compound 13 could be obtained through the reaction of compound 3 with carbon disulfide in basic medium. Alkylation of compound 13 afforded the corresponding alkylthio derivative 14. Reaction of 1-methyl-4-nitropyrrole-2-carboxylic acid (15) with thiosemicarbazide and phosphorus oxychloride gave 2-amino-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole (16). Sandmeyer reaction of compound 16 yielded 2-chloro-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole (17). Refluxing of the latter with thiourea afforded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazotine-4(H)-5-thione (18). Alkylation of compound 18 gave the corresponding alkylthio derivative 19. Oxidation of the latter with hydrogen poroxide in acetic acid yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-5-methylsulfonyl-1,3,4-thiadiazole (20).