Efficient Synthesis of Ortho- or Para-aminophenol via Diazo Coupling Reduction Process and Scalable Manufacturing Chlorzoxazone

Abstract

Aminophenol are versatile intermediates widely utilized in the pharmaceutical, dye and pigment, and materials science industries. Conventional synthetic methods typically involve harsh reaction conditions, use expensive noble metal catalysts, or generate a large amount of environmentally unfriendly "three wastes". In this study, we systematically optimized the diazo coupling reduction process and established an efficient and practical synthetic route for aminophenol synthesis. This protocol features a broad substrate scope (20 examples), mild reaction conditions, straightforward post-reaction treatment, and excellent yields (up to 96%). The application of this process was further extended to the development of a kilogram-scale synthesis of the muscle relaxant chlorzoxazone. Notably, the overall three-step yield reached up to 76.5%.