Synthesis and Reactions of New Fused Heterocycles Derived from 5-Substituted-4-Amino-3-Mercapto-(4H)-1,2,4-Triazole with Biological Interest

The reaction of thiocarbohydrazide with carboxylic acids at the melting temperature allows an improved preparation of 5-substituted-4-amino-3-mercapto 1,2,4-triazoles 1(a-g). Compound 1(a) reacted with 2-bromopropionic acid to give acid derivative 2. The latter was reacted with a mixture of acetic anhydride and triethylamine to afford the mesoionic compound 3. Heating of compound 3 in ethanol gave the ester derivative 4, which on alkaline hydrolysis in methanol gave ketone derivative 5. Substituted 1,2,4-triazolo [3,4-b]-6H-1,3,4-thiadiazine 6(h,i) and 7 were synthesized by reaction of 1(a) with acetylacetone, ethyl acetoacetate and chloroacetamide. Heterocyclic systems 8 and 9 were prepared through the reaction of 1(a) with 2,3-dichloro-1,4-naphthoquinone and 2,3-dichloroquinoxaline. In addition, thenoyl isothiocyanate, thenoyl chloride, 2-thiophenecarbaldehyde, and p-chlorophenyl isocyanate reacted with compound 1(a) to afford 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole ring system 10, 11, and urea derivative 12. 1,2,4-Triazolo[3,4-b]-5H-pyrazole derivatives 14(j,k) were prepared through the reaction of compound 1(a) with 3-chloro-2,4-pentandione and ethyl-2-chloroacetoacetate. Compound 14(j) was treated with hydrazine to afford products 15, 16, and 17 depending on the type of hydrazine derivative and reaction conditions. Compound 19 was synthesized by refluxing of compound 14(j) with hydroxylamine hydrochloride to afford the corresponding oxime derivative 18 followed by treatment with thenoyl chloride.