Sulfur‐Assisted Deprotection of Methylene Nitrile Group: One‐Pot Synthesis of 4‐Substituted‐2H‐1,2,3‐triazoles

An operationally simpler one‐pot synthesis of 4‐substituted‐2H‐1,2,3‐triazole is demonstrated by unusual deprotection of methylene nitrile group using elemental sulfur. The strategy involves click reaction followed by deprotection of methylene nitrile group using elemental sulfur. Broad functional group tolerance with good to excellent yielding method has been developed. Also, N‐acyl‐cyclopentyl and hexyl amide 1,2,3‐triazole derivatives 6 m and 6 n were evaluated for their in vitro quorum sensing inhibition (QSI) activity against P. aeruginosa. Compounds 6 m and 6 n exhibited significant QSI activity with 49.7% and 50.7% in P. aeruginosa MH602 at 250 μM, respectively. We also report in vitro toxicity of these compounds against human embryonic kidney cell line. 6 m and 6 n are found to be less toxic in HEK 293 cell line. For the first time we report, synthesis of 4‐substituted‐2H‐1,2,3‐triazole employing, less expensive, S8 to deprotect methylene nitrile group. Yields ranged from 62–91%. N‐acyl‐cyclopentyl and hexyl amide 1,2,3‐triazole derivatives 6 m and 6 n exhibited significant QSI activity with 49.7% and 50.7% in P. aeruginosa MH602 reporter strain at 250 μM, respectively. Both 6 m and 6 n were not found to be toxic in normal human embryonic kidney cell line (HEK 293).