Synthesis of 5-halogenated 1,2,3-triazoles under stoichiometric Cu(I)-mediated azide-alkyne cycloaddition (CuAAC or 'Click Chemistry')

Abstract

Glucosylated heterocycles have been identified as potent inhibitors of glycogen phosphorylase (GP), a biomolecular target for the treatment of hyperglycemia and therefore type 2 diabetes. Several glucosylated triazoles have been evaluated as GP inhibitors and additional structures are being considered in the present study with the introduction of a substituent at the 5-position of the triazole ring. The 1,3-dipolar cycloaddition of azide and alkyne using stoichiometric amounts of Cu(I) halides favored the formation of the 5-halogenated 1,2,3-triazoles. The influence of the copper halide introduced (CuI, CuBr, or CuCl) provided different results and more specifically for the CuCl system which afforded a dimeric 5,5'-bistriazole in good yield (56%) as evidenced by crystallographic data.