An efficient synthesis of new 3,5-bis(2-arylthiazol-4-yl)-1,2,4-oxadiazole derivatives and their antimicrobial evaluation

A new series of 3,5-bis(2-arylthiazol-4-yl)-1,2,4-oxadiazole (8a-o) has been synthesized by modified reaction conditions. The reaction of ester 7a with N '-hydroxy-2-phenylthiazole-4-carboximidamide 6a using NaOH in DMSO gave the formation of product 8a up to 40% yield. In the second method, the reaction with K2CO3 in toluene at reflux conditions gave a 50% yield. In the third method, the reaction condition was modified. The ester 7a was hydrolyzed to acid 9a. The reactions of acid 9a using N,N-dimethyl amino pyridine (DMAP) in N,N-dimethylformamide (DMF), followed by the addition of N-(3-dimethylaminopropyl)-N '-ethylcarbodiimide hydrochloride (EDC center dot HCl), and then N '-hydroxy-2-phenylthiazole-4-carboximidamide 6a, furnished a 65% yield of 8a. The compounds 8b-o were synthesized using DMAP and EDC center dot HCl as coupling reagents and gave 60%-72% yields. The structure of newly synthesized compounds was confirmed by spectral analysis. The synthesized compounds were screened for in vitro antimicrobial activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM2063), Staphylococcus albus (NCIM 2178), Candida albicans (NCIM 3100), and Aspergillus niger (ATCC 504). Among the 8a-o derivatives, eight compounds 8c, 8e, 8f, 8g, 8i, 8j, 8k, and 8l showed good activity S. albus with a MIC 31.25-62.5 mu g/mL.