In Situ Electrosynthesis of Active Chlorine for Selective Aromatic Chlorination

Aromatic chlorination is highly valuable because it enhances lipophilicity, increases bioactivity, and enables the selective blocking of metabolic sites. However, conventional methods often rely on toxic chlorine gas, which poses significant environmental and safety risks. Herein, we report an in situ electrochemical chlorination strategy that enables the generation of active chlorine species (Cl2/HOCl) for the selective chlorination of aromatic compounds. Using benzyl alcohol as a model substrate, electrochemical analyses identified a titanium electrode coated with iridium and ruthenium (Ti/IrRu) as the most effective, exhibiting high chlorination efficiency with minimal byproduct formation. Selective oxidation of Cl− to Cl2, followed by its immediate conversion to HOCl, was achieved while suppressing oxygen evolution and minimizing undesired substrate oxidation. Theoretical calculations showed that the strong adsorption of benzyl alcohol suppresses substrate oxidation, while the Cl adsorption being more favorable than OH enables fast chloride oxidation and suppresses oxygen evolution, consistent with the experimentally observed selectivity of the Ti/IrRu electrode. The versatility of the method was further demonstrated across a broad range of aromatic substrates, including drug molecules such as clofibrate and aniracetam, thereby demonstrating its potential for late-stage functionalization in pharmaceutical and fine chemical synthesis. Furthermore, supported by the excellent stability of the Ti/IrRu electrode, we developed a continuous electrochemical flow-cell system for the in situ generation of Cl2/HOCl, thereby facilitating real-time electrochemical chlorination. Based on fundamental electrochemical analysis, the system demonstrates the feasibility of seawater-based halogenation and establishes a practical, scalable platform toward continuous electrochemical synthesis.