Metal-free selective alcohol oxidation via quinazolinone: mechanistic insights and sustainable applications

Abstract

The oxidation of alcohols has been extensively studied over the years; however, the development of metal-free, selective methods for alcohol oxidation—particularly those enabling precise transformation into aldehydes or ketones—remains a significant challenge. Herein, we report a new organic oxidant that facilitates alcohol oxidation via acid-catalyzed transfer hydrogenation of quinazolin-2(1H)-one (HDQ). This eco-friendly and scalable process offers high selectivity, a straightforward workup, and broad substrate scope. Mechanistic studies, supported by isotope labeling and density functional theory (DFT) calculations, were conducted to elucidate the reaction pathway. Notably, this approach provides a dual-function pathway, directly yielding a diverse array of aldehydes and ketones while simultaneously producing 3,4-dihydroquinazolin-2(1H)-one (DHQZ), a privileged scaffold in small-molecule drug design. This novel alternative to conventional oxidation methods offers a sustainable solution suitable for large-scale chemical production.