Huang Chong, Xu Hai-Chao
State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province, and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
Angew Chem Int Ed Engl. 2025 Aug 11;64(33):e202504612. doi: 10.1002/anie.202504612. Epub 2025 Jun 16.
Aromatic aldehydes are pivotal synthetic intermediates with applications in fine chemicals, pharmaceuticals, agrochemicals, and advanced materials. Although the oxidation of methylarenes represents an ideal route to aromatic aldehydes due to the availability of starting materials, existing methods face significant challenges, including reliance on hazardous oxidants, costly catalysts, poor scalability, and limited compatibility with electron-deficient substrates. To address these limitations, we report a practical and scalable electrochemical method for the oxidation of electron-deficient methylarenes to access aromatic aldehydes, eliminating the need for chemical oxidants or homogeneous transition-metal catalysts. This approach operates under industrially viable conditions-high current densities (75 mA cm⁻), minimal electrolyte loading (0.05 equiv), and operation in an undivided cell without additives-to produce aromatic acetals, which are readily hydrolyzed to the corresponding aldehydes. The use of minimal electrolyte not only reduces costs and simplifies product isolation but also significantly enhances anodic oxidation selectivity, ensuring high efficiency and practicality. This protocol exhibits a broad substrate scope, compatibility with both batch and continuous flow systems, and exceptional scalability, as demonstrated by successful kilogram-scale synthesis.
芳香醛是关键的合成中间体，在精细化学品、制药、农用化学品和先进材料领域有广泛应用。尽管由于起始原料的可得性，甲基芳烃的氧化是合成芳香醛的理想途径，但现有方法面临重大挑战，包括依赖危险氧化剂、昂贵的催化剂、可扩展性差以及与缺电子底物的兼容性有限。为了解决这些限制，我们报道了一种实用且可扩展的电化学方法，用于将缺电子甲基芳烃氧化以制备芳香醛，无需化学氧化剂或均相过渡金属催化剂。该方法在工业可行的条件下运行——高电流密度（75 mA cm⁻²）、最低电解质负载量（0.05当量）以及在无添加剂的无隔膜电解池中操作——以生成芳香缩醛，这些缩醛可轻松水解为相应的醛。使用最低量的电解质不仅降低了成本并简化了产物分离，还显著提高了阳极氧化选择性，确保了高效率和实用性。该方案具有广泛的底物范围，与间歇式和连续流系统均兼容，并且具有出色的可扩展性，千克级规模的成功合成证明了这一点。
