An efficient and green synthesis of 2-phenylquinazolin-4(3H)-ones via t-BuONa-mediated oxidative condensation of 2-aminobenzamides and benzyl alcohols under solvent- and transition metal-free conditions

Abstract

Abstract Quinazolinone synthesis usually requires employing sensitive substrates, hazardous solvents, large excess oxidants, and expensive catalysts. In this study, an efficient and environmentally benign pathway was developed to synthesize 2-phenylquinazolin-4(3H)-one via oxidative coupling between commercially available and stable chemicals, including 2-aminobenzamide and benzyl alcohol without toxic oxidizing agents and transition-metal catalysts. A high yield of the desired product (up to 84%) was obtained at 120°C for 24 h in the presence of oxygen as a green oxidant and t-BuONa as a base. Importantly, the study scope was expanded toward successfully producing various 2-phenylquinazolin-4(3H)-one derivatives in moderate-to-good yields. Furthermore, control experiments proposed that the conversion involved the initial partial oxidation of benzyl alcohol to the benzaldehyde intermediate under basic conditions, followed by the condensation, intramolecular nucleophilic addition, and oxidative dehydrogenation to 2-phenylquinazolin-4(3H)-one.