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

Shaker Awad Abdul Hussein
a; Ammar Abdul Razzak M. Kubba
b

Abstract

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

Author(s): Shaker Awad Abdul Hussein a and Ammar Abdul Razzak M. Kubba b

In this study, new derivatives of 2,5-dimercapto- 1 ,3,4-thiadiazole were synthesized by cyclization a nd coupling reactions, in a satisfactory yield. The reaction of 2,5-dimercapto-1,3,4-thiadiazole with ethyl bromoa cetate in absolute ethanol afforded the ester derivative (1), which was treated with hydrazine hydrate to give t he corresponding carbohydrazide (2). The carbohydrazid e (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) r eacted with acetyl acetone and gave dimethyl pyrazo le derivative (4). Refluxing of carbohydrazide (2) with anhydride s; like succinic, maleic and phthalic anhydrides, a fforded the compounds (5), (6) and (7) respectively. Treatment of carbohydrazide (2) with tetrahydrofuran in glaci al acetic acid gave the compound (9). The reaction of carbohydrazi de (2) with phenyl isothiocyanate, furnished compou nd (10), which is successfully cyclized upon addition of 5% NaOH under reflux, to give the corresponding mercap to triazole derivative (11). Also, a series of amino acid methy l esters (12a-c) and dipeptides (14a-c) attached to the heterocyclic ring were successfully synthesized, starting from a mino acid esters and azides (2a,13a), respectively. All the synthesized compounds were screened for their in vitro antimicrobial activities against six pathogenic bac terial 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 mod erate antibacterial activities, and both compounds (9 and 14c) exhibited the most poten t antifungal activities against Aspergillus terreus . All the synthesized compounds were in good agreement with e lemental and spectral data ( FT-IR, 1 HNMR spectroscopy).

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