Tandem synthesis of [1,2,4]-triazoles mediated by iodine-a regioselective approach

A tandem regioselective one-pot synthesis of 3-amino-[1,2,4]-triazoles has been achieved from 1,3-disubstituted thioureas using molecular iodine. In this one-pot strategy, the intermediate carbodiimide generated in situ from thiourea upon reaction with HCONHNH2 gives diaryl/alkylhydrazinecarboximidamide or acylureidrazone, which then undergoes an intramolecular cyclodehydration to afford the corresponding 3-amino-[1,2,4]-triazole. The product regioselectivity for unsymmetrical 1,3-disubstituted thioureas correlate well with the pK(a)s of the parent amines attached, in which the amine having higher pK(a) goes to the ring nitrogen while the other nitrogen remains flanked as an exocyclic nitrogen of the triazole core. This method is milder and environmentally sustainable giving good to excellent yields of the desired products. (C) 2012 Elsevier Ltd. All rights reserved.