Unveiling the reaction mechanisms of the synthesis and the excited state intramolecular proton transfer of 2‐(2′‐hydroxyphenyl)imidazo[1,2‐a]pyridine

A.P. and A.P.-Q. are Serra Húnter Fellows. A.P. received ICREA Academia Prize 2019. We thank the Ministerio de Ciencia e Innovación for projects PID2021-127423NB-I00 (to A.P.), PID2020-113711GB-I00 (to A.P.-Q. and M.S.), and MCIN/AEI/10.13039/501100011033 to A.P.-Q and to the Generalitat de Catalunya for project 2021SGR623. R.M.-C. thanks the Spanish government for the predoctoral FPU20/00707.

Abstract

Given its wide variety of applications in the pharmaceutical industry, the synthesis of imidazo[1,2-a]pyridines has been extensively studied since the beginning of the last century. Here, we disclose the mechanism for the synthesis of imidazo[1,2-a]pyridines by means of the Ortoleva-King reaction. We also reveal the reaction pathway leading to the formation of a iodinated byproduct, demonstrating the challenge of preventing the formation of such a byproduct because of the low energy barrier to access it. Moreover, quantum chemistry tools were employed to investigate the mechanism of intramolecular proton transfer in the excited state, and connections with aromaticity were explored.

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