Direct Access to Highly Functionalised Benzimidazoles and Benzoxazoles from a Common Precursor

Abstract

Benzoxazole and benzimidazole are commonly encountered heterocycles in medicinal chemistry and their functionalisation around 1-, 2-, 5-, and/or 6-positions provides a wide range of molecules of biological interest. In this manuscript, a straightforward preparation of diversely and highly substituted benzimidazoles and benzoxazoles on these positions, from a common starting material, a 3,3-dibromoacrolein, is described. Such acrolein derivatives are almost never described in the literature or used as ‘building-block’ for organic synthesis. The double electrophilicity of this substrate was found to be advantageous for condensation with two equivalents of various 1,2-diaminobenzene or 2-aminophenol derivatives. This one-pot reaction performed under metal-free and mild conditions allows the creation of three new carbon–heteroatom bonds and affords the desired heterocycles.

Recent achievements in the synthesis of benzimidazole derivatives

“…Garrido et al demonstrated a straightforward approach for the preparation of functionalized benzimidazoles by the reaction between 3,3-dihalogenoacrolein and diaminobenzenes. 170 The one-pot reaction afforded products in good yields under metal-free and mild conditions ( Scheme 101 ). A plausible reaction mechanism was also described.…”