Sono- and Mechanochemical Tandem Synthesis of Diversely Functionalized 1,2,4-Thiadiazoles: A Robust and Straightforward Dual Synthetic Approach.

We herein report a sonochemistry- and mechanochemistry-driven dual synthetic strategy as a convenient alternative approach for a diverse array of biorelevant functionalized N-fused 1,2,4-thiadiazoles (3)/5-amino-1,2,4-thiadiazoles (5) from the tandem reaction between pyridine-2-amines/benzimidamide derivatives (1/4) and phenyl isothiocyanates (2) in the presence of N-iodosuccinimide (NIS), involving intermolecular dehydrogenative C-N coupling, followed by intramolecular S-N bond cyclization. Both synthetic protocols provide straightforward, practical, and environmentally benign routes to this important class of biologically and synthetically valuable heterocycles. The noteworthy advantages of this dual synthetic approach include mild reaction conditions, the avoidance of using metal catalysts and/or oxidants, organic solvents, and heating, significantly shorter reaction times (in minutes), good to excellent yields with high regioselectivity, a broad substrate scope, excellent functional group tolerance, reusability of the solid surface (in the mechanochemical method), and facile gram-scale applications. Additionally, the synthetic utility of the methodology was demonstrated through the transformation of some selected 1,2,4-thiadiazole derivatives to a variety of structurally diverse and biologically relevant molecular scaffolds.