A deep dive into mechanochemical organic reactions by accurate crystallographic analysis via TAAM refinement

Abstract

An original oxidative functionalization of 8-aminoquinolines in the presence of an organic peroxide under batch conditions has been recently reported. It was proposed that the reaction involved a highly unusual C8-to-C7 amino group shift, coupled with the concomitant oxygenation at the C8 position of the heterocycle. Although single crystal X-ray diffraction was performed with acceptable statistical parameters, we propose a substantial reinterpretation of the actual structure by an accurate refinement of data via the transferable aspherical atom model (TAAM). Indeed, we unambiguously clarify that no amino-group-shift took place and that direct oxygenation at C7 occurred instead. Moreover, we report herein that this reactivity could be also performed under mechanochemical conditions, suggesting the feasibility to perform similar oxidation processes minimizing chemical waste.