Synthesis and biological activities of methylenebis-4H-1,2,4-triazole derivatives

Authors: YILDIZ UYGUN, HACER BAYRAK, HAVVA ÖZKAN

Abstract: 5,5'-Methylenebis(4--phenyl-4H-1,2,4-triazole-3-thiol) (2) was synthesized starting from hydrazinecarbothioamide compound (1). Treatment of compound 2 with ethyl bromoacetate produced diethyl 5,5'-{methylenebis[(4-phenyl-4H-1,2,4-triazole-5,3-diyl)thio]}diacetate (3), which was converted to the corresponding diacetohydrazide derivative (4) by treatment with hydrazine hydrate. The reaction of compound 4 with several aldehydes produced the corresponding arylidene hydrazides, 5a--d. Syntheses of Mannich bases 6a--c were carried out by the treatment of compound 2 with several amines in the presence of formaldehyde. (4{[5-({5-[(4-Amino-2-chlorophenyl)thio]-4-phenyl-4H-1,2,4-triazol-3-ylmethyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio}-3-chlorophenyl)amine (8) was prepared by reduction of 2 nitro groups of 3,3' -methylenebis{5-[(2-chloro-4-nitrophenyl)thio]-4-phenyl-4H-1,2,4-triazole} (7) that were obtained from the condensation of 2} with 3,4-dichloronitrobenzene. The newly synthesized compounds were screened for their antimicrobial activities; some of them were found to be active towards the test microorganisms as the results demonstrated that the synthesized compounds exhibited a broad spectrum of activity with minimum inhibitory concentration (MIC) values of 31.3--500 \mu g/mL against gram-positive and gram-negative bacteria, Candia albicans and Saccharomyces cerevisiae. All compounds displayed lower activity in this series against the microorganisms with MIC values of 31.3--500 \mu g/mL than did the compared control drugs of ampicillin, streptomycin, and fluconazole.

Keywords: 1,2,4-Triazole, morpholine, furan, Schiff base, Mannich base, antimicrobial activity

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