New thiophene-1,2,4-triazole-5(3)-ones: Highly bioactive thiosemicarbazides, structures of Schiff bases and triazole-thiols

Key compound 2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4- tiazole-1-yl) acetohydrazide (3) was synthesized by reacting hydrazine hydrate with ethyl-2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4-tiazole- 1yl)acetate (2), obtained in basic media from 4-amino-5-(thiophene-2-ylmethyl)- 2H-1,2,4-triazole-3(4H)-one (1). Compound 3 was converted to thiosemicarbazide derivatives (4a-d) and Schiff base derivatives 6a-e and 7a-e. The treatment of compound 4 with NaOH gave 4-amino-2-((4-(4-aryl)-5-mercapto-4H-1,2,4-triazole-3- yl)methyl)-5-(thiophene-2-ylmethyl)-2H-1,2,4-triazole-3(4H)-ones (5a-d). All newly compounds, well characterized by elemental analyses, IR, 1H NMR, 13C NMR and mass spectral studies were tested for their antioxidant and antimicrobial activities. Thiosemicarbazide derivatives (4a-d) were highly active in two antioxidant tests with 69.0-88.2% DPPH scavenging and 503-1257 μM TEAC values, while the others showed lower or no activity. The results of the two antioxidant tests correlated well. Moreover, Thiosemicarbazide derivatives (4a-d) also showed antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Mycobacterium smegmatis. Thiosemicarbazide group deserves attention in the synthesis of bioactive compounds.