Nanobubble-Driven Selective Oxidation of Toluene to Benzaldehyde

Abstract Selective oxidation of C(sp3)-H bonds remains a longstanding challenge in organic synthesis, especially under environmentally friendly conditions. Conventional strategies typically rely on harsh oxidants or complex catalysts, limiting their sustainability and scalability. Nanobubbles can generate highly reactive species during collapse because of their unique physicochemical properties. In particular, the gas–liquid interface of nanobubbles has attracted increasing attention for its ability to concentrate reactants and facilitate radical-driven transformations. Herein, we report a light-assisted ultrasound strategy in which nanobubbles produce hydroxyl radicals as the primary reactive species for C(sp3)-H bond activation under ambient conditions, without requiring additional oxidants or catalysts. With toluene as a model substrate, the method afforded 24.3% conversion and 61.6% selectivity toward benzaldehyde within 4 h. Mechanistic investigations, including isotope-labeling, radical-quenching experiments, and density functional theory (DFT) calculations, revealed that hydroxyl radicals originate from both water and dissolved oxygen and selectively abstract benzylic hydrogen atoms. This study establishes an efficient and environmentally friendly route for C–H bond oxidation while offering new mechanistic insights into radical generation at gas–liquid interfaces. We anticipate that this nanobubble-driven strategy will advance the development of green chemical transformations and may provide opportunities for the development of sustainable oxidation processes.