High Regioselective Synthesis of N²-Substituted-1,2,3-triazole via N-Sulfonyl-1,2,3-triazole Coupling with Alcohol Catalyzed by in-situ Generated Sulfonic Acid

The green and highly efficient synthesis of N²-substituted 1,2,3-triazoles remains challenging due to the lower electron density at the N²-atom than that at two terminal nitrogen atoms (N¹ and N³) of the triazole heterocycle. Cheap and easily available alcohols were developed as starting points to couple with N-sulfonyl-1,2,3-triazole instead of halogenated reagents catalyzed by in-situ generated sulfonic acid. The resulting products, N²-substituted 1,2,3-triazoles, were obtained with high regioselectivity and in good yields (68%～83%) without any additional catalysts or additives. The reaction has a broad substrate adaptability and functional group compatibility, including aryl benzyl and alkyl alcohols. Preliminary mechanistic studies indicate that methanesulfonic acid (MsOH) which in situ produced by the hydrolysis of N-sulfonyl-1,2,3-triazoles promoted the reaction, and high regioselectivity was promoted through the thermally stable intermediate N²H-1,2,3-triazole.