Base-promoted transition-metal-free synthesis of quinazolinones with antioxidant activity

Abstract

Herein, we describe a transition-metal-free, base-promoted protocol for the synthesis of quinazolinones that utilizes polyethylene glycol 200 (PEG-200) as the reaction medium. The process operates under mild reaction conditions, providing a diverse set of quinazolinone scaffolds in good yields with operational simplicity. The established procedure provides access to bioactive quinazolinones, several of which showed remarkable antioxidant activity. In contrast, (4-(trifluoromethyl) phenyl) quinazolin-4(3H)-one and 6-chloro-2-phenylquinazolin-4(3H)-one showed the highest IC₅₀ values of 45.10 and 57.97 μg mL⁻¹ in the DPPH radical scavenging assay. Density functional theory (DFT) calculations were also conducted to provide a mechanistic understanding about the transformation. Thus, this dual-focused work not only provides an effective synthetic pathway to quinazolinones but also identifies lead compounds with noteworthy antioxidant properties for further biological investigation. These results pave the way for manufacturing innovations in the near future.