Continuous Synthesis of Aryl Amines from Phenols Utilizing Integrated Packed‐Bed Flow Systems

Aryl amines are important pharmaceutical intermediates among other numerous applications. Herein, an environmentally benign route and novel approach to aryl amine synthesis using dehydrative amination of phenols with amines and styrene under continuous‐flow conditions was developed. Inexpensive and readily available phenols were efficiently converted into the corresponding aryl amines, with small amounts of easily removable co‐products (i.e., H2O and alkanes), in multistep continuous‐flow reactors in the presence of heterogeneous Pd catalysts. The high product selectivity and functional‐group tolerance of this method allowed aryl amines with diverse functional groups to be selectively obtained in high yields over a continuous operation time of one week. Flow with it: Dehydrative amination of phenols under continuous‐flow conditions has been developed. In an integrated packed‐bed flow system containing heterogeneous Pd catalysts, phenols reacted with amines to obtain aryl amines and small amounts of easily removable co‐products. The method has high product selectivity and excellent functional‐group tolerance, so that variously substituted aryl amines can be selectively prepared in high yields.