Scalable and Practical Electrooxidation of Electron-Deficient Methylarenes to Access Aromatic Aldehydes.

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.