We developed a highly regioselective base-induced synthesis of N 2-substituted 1,2,3-triazoles from N-sulfonyl-1,2,3-triazoles and alkyl bromides/alkyl iodides at room temperature. We propose an SN2-like mechanistic pathway to explain the high N 2-regioselectivity. The protocol features a broad substrate scope and generates products in good to excellent yields (72–90%).

The green and highly efficient synthesis of N 2 -substituted 1,2,3-triazoles remains challenging due to the lower electron density at the N 2 -atom than that at two terminal nitrogen atoms (N 1 and N 3 ) 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, N 2 -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 N 2 H-1,2,3-triazole.

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A regioselective electrochemical C−H amination method to synthesize N 2 -substituted 1,2,3-triazole using easily accessible ethers has been developed. Various substituents, including heterocycles, have a good tolerance, and 24 examples were obtained in moderate to good yields. Control experiments and DFT calculation investigations demonstrate that the electrochemical synthesis undergoes a N-tosyl 1,2,3-triazole radical cation process promoted by the single-electron transfer of the lone pair electrons of the aromatic N-heterocycle, and the desulfonation is responsible for the high N 2 -regioselectivity.