Abstract

An efficient regio-selective aryl CH activation and tandem o-hydroxylation method for 2-arylbenzimidazoles has been developed by using a Pd(OAc)(2)/oxone/Cs2CO3 catalytic system. This reaction was successfully optimized by using various catalysts, oxidants, bases, and solvents to achieve the desired products in good yields. Further, preliminary mechanistic studies were conducted to examine the source of oxygen for this transformation. Gratifyingly, this catalytic system is also suitable for the introduction of various alkoxy groups, and delivered the products in good yields. The synthesized compounds were evaluated for their cytotoxic activity in selected human cancer cell lines. Some of the representative compounds (1f, 2f, 3f and 4f) have significant IC50 values ranging from 1-10M. Structure-activity relationship studies indicate that in these compounds the ethoxy substituent is probably responsible for the improved activity. In addition, the DNA-binding potential of these compounds was also investigated by UV/vis, fluorescence, and circular dichroism spectroscopy.