Photoinduced regioselective halogenation of 1-alkyl/benzyl-3-phenylquinoxalin-2(1H)-ones in water

Abstract

A sustainable visible-light-driven protocol for the regioselective mono-halogenation of 1-substituted-3-arylquinoxalin-2(1H)-ones has been developed. In contrast to previously reported thermally assisted or microwave-promoted methods, the present transformation proceeds efficiently under mild conditions at room temperature in water, without the requirement for elevated temperatures, acid additives, or energy-intensive activation. The reaction employs a dual catalytic system consisting of Pd(OAc)₂ and water-soluble Eosin Y, together with 1,3-dihalo-5,5-dimethylhydantoin (DXDMH) as a safe and efficient halogenating reagent. The methodology affords synthetically valuable yields (64–89%) over a broad substrate scope with excellent regioselectivity and good functional-group tolerance. Mechanistic studies, including radical trapping experiments, light on/off investigations, and control reactions, suggest a cooperative pathway involving palladium-mediated C–H activation and photoredox-induced generation of halogen radicals. The regioselective halogenation pattern was unequivocally established by single-crystal X-ray diffraction analysis, while the practicality of the protocol was demonstrated through a 0.5 g scale reaction. Overall, this work provides an operationally simple, environmentally benign, and fundamentally distinct alternative to conventional halogenation strategies, offering a valuable contribution to sustainable photocatalytic C–H functionalization.