One-pot synthesis of 3,5-disubstituted 1,2,4-thiadiazoles from nitriles and thioamides via I-mediated oxidative formation of an N-S bond.

A simple and practical method for I-mediated one-pot synthesis of 3-alkyl-5-aryl-1,2,4-thiadiazoles has been developed; the one-pot reaction includes sequential intermolecular addition of thioamides to nitriles, and intramolecular oxidative coupling of N-H and S-H bonds mediated by molecular iodine. Meanwhile the protocol uses readily available nitriles and thioamides as the starting materials, molecular iodine as the oxidant, and generates various 1,2,4-thiadiazoles in moderate to good yields with a wide array of functional groups. This method is an efficient approach for the synthesis of unsymmetrically disubstituted 1,2,4-thiadiazoles.