Syntheses of substituted-oxazolo-1,3,4-thiadiazoles, 1,3,4-oxadiazoles,and 1,2,4-triazoles

Starting from readily available methyl 5-methyloxazole-4-carboxylate ( 1 ) and 4-methyl-5-oxazolylcar-boxylic acid hydrazide ( 11 ) the title compounds were prepared. The reaction of compound 1 with hydrazine hydrate afforded the corresponding hydrazide 2 . The reaction of compound 2 with formic acid yielded 1-formyl-2-(5-methyloxazole-4-carboxyl)hydrazine ( 3 ). Refluxing of the latter with phosphorus pentasulfide in xylene gave compound 5 in 62% yield. The reaction of compound 3 with phosphorus pentoxide afforded compound 4 . Starting from hydrazide 11 , compounds 13 and 14 were prepared similarly. Reaction of compound 2 with substituted isothiocyanate yielded compound 9 which was cyclized in basic medium to 4-alkyl-5-(5-methyl-4-oxazolyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione ( 10 ). The isomer 19 was prepared similarly. Methylation and subsequent oxidation of compound 19 gave compound 21 . Reaction of the acid 7 with thiosemicarbazide in the presence of phosphorus oxychloride gave 2-amino-5-(5-methyl-4-oxazolyl)1,3,4-thiadiazole ( 8 ). 2-Amino-5-(4-methyl-5-oxazolyl)-1,3,4-thiadiazole ( 17 ) was prepared from acyl chloride 15 by the usual method.