Copper-catalyzed click synthesis of 1,2,3-triazole-linked benzimidazole

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, also known as the click reaction , has become one of the most important reactions used for the preparation of 1,2,3-triazoles [1]. The 1,2,3-triazoles showed significant antiproliferative against a wide variety of human cancer cell lines, including those that are multidrug resistant [2]. The benzimidazole skeleton is an important class of nitrogen-containing heterocyclic compounds with a significant pharmacological efficiency including the anti-bacterial, and anti-viral properties [3]. On the other hand, when 1,2,3-triazoles and benzimidazole are linked by copper-catalyzed click reactions at the specific ring positions of bi- or tri-heterocyclic containing new molecules, interesting physiological proprieties are observed. Herein, we now wish to investigate a straightforward synthesis of new derivatives of the 1,2,3-triazole-linked benzimidazole via the copper-catalyzed click reactions (Scheme 1).A mixture of 2-(methylthio)-1H-benzo[d]imidazole (1), K2CO3, and propargyl bromide was stirred in DMF for 24h at room temperature. The solvent was evaporated to dryness, the product was washed with water. The resulting solid substance wasfiltered to afford 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (2) in good yield. The click reaction of compound (2) with various alkyl halides, sodium azide, in the presence of 5 mol% of Cu(OAc)2 and 10 mol% of sodium ascorbate at room temperature in ethanole, to afford the compound (3) were obtained in good-to-high yields.