Direct Synthesis of 2‐Aryl Quinolone Derivatives via Oxidative Cyclization: Batch Versus Continuous‐Flow

ABSTRACT

Efficient access to structurally important N‐heterocycles continues to be a major focus in synthetic chemistry owing to their broad relevance in medicinal and functional molecule synthesis. In this study, we report an efficient and practical metal‐free p‐TsOH·H ₂ O‐promoted protocol for the synthesis of 2‐arylquinolones under batch and continuous‐flow conditions. The strategy provides two synthetic routes to 2‐arylquinolones; direct cyclization of readily accessible 2‐aminochalcones and a convenient one‐pot synthesis from 2‐aminoacetophenones and aldehydes, thereby avoiding the need to pre‐isolate the aminochalcone intermediates. The transformation proceeds effectively and accommodates a broad range of substrates bearing electron‐donating as well as electron‐withdrawing groups, delivering the desired 2‐arylquinolones in good to excellent yields. Importantly, translation of the methodology to continuous‐flow processing enabled rapid and selective access to both 2‐phenyl‐2,3‐dihydroquinolin‐4(1 H )‐ones and 2‐arylquinolones within minutes by adjusting the reaction atmosphere. The scalability and robustness of the protocol are demonstrated through gram‐scale experiments, highlighting its practical utility for synthetic applications.