Synthesis, characterization and antimicrobial activity of new 2,5-disubstituted-1,3,4-thiadiazole derivatives

Abstract

In this study, new derivatives of 2,5-dimercapto- 1,3,4-thiadiazole were synthesized by cyclization and coupling reactions, in a satisfactory yield. The reaction of 2,5-dimercapto-1,3,4-thiadiazole with ethyl bromoacetate in absolute ethanol afforded the ester derivative (1), which was treated with hydrazine hydrate to give the corresponding carbohydrazide (2). The carbohydrazide (2) was reacted with two and four equivalents of methyl acetoacetate, and afforded the corresponding methyl pyrazolone (3) and pyranopyrazole (8), derivatives, respectively. Furthermore, the carbohydrazide (2) reacted with acetyl acetone and gave dimethyl pyrazole derivative (4). Refluxing of carbohydrazide (2) with anhydrides; like succinic, maleic and phthalic anhydrides, afforded the compounds (5), (6) and (7) respectively. Treatment of carbohydrazide (2) with tetrahydrofuran in glacial acetic acid gave the compound (9). The reaction of carbohydrazide (2) with phenyl isothiocyanate, furnished compound (10), which is successfully cyclized upon addition of 5% NaOH under reflux, to give the corresponding mercapto triazole derivative (11). Also, a series of amino acid methyl esters (12a-c) and dipeptides (14a-c) attached to the heterocyclic ring were successfully synthesized, starting from amino acid esters and azides (2a,13a), respectively. All the synthesized compounds were screened for their in vitro antimicrobial activities against six pathogenic bacterial strains, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia and three fungal strains, Aspergillus niger, Aspergillus terreus and Candida albicans, by well diffusion method. These compounds showed moderate antibacterial activities, and both compounds (9 and 14c) exhibited the most potent antifungal activities against Aspergillus terreus. All the synthesized compounds were in good agreement with elemental and spectral data (FT-IR,1HNMR spectroscopy).