A versatile synthesis of bis[2-(2′-hydroxylphenyl)benzoxazole] derivatives as zinc sensors

Abstract

A versatile synthetic route has been developed to prepare 2, 5-bis(benzoxazole-2-yl)benzene-1,4-diol derivatives 2. Although one of the derivatives (2b) has recently been shown to exhibit an excellent response to Zn²⁺ cations, the low yielding synthetic route will likely prevent its wide application. This report describes an improved synthetic procedure to obtain 2, thereby making this class of compounds available for biologically relevant studies. An effective synthesis has been developed for 2-aminophenol derivative 6, which bears a carboxylate group in the desired position. The strategy allows construction of bis(benzoxazole) compound 5, where the built-in ester group can be easily converted to either a hydroxymethyl or a bromomethyl group to introduce the zinc-chelating ligand.