Catalyst-free synthesis of unsymmetrical ureas from COS and amines: a strategy for selectivity regulation†

Abstract

A novel and mild method for the highly selective synthesis of unsymmetrical ureas from amines and COS has been established. This method effectively synthesizes unsymmetrical ureas from combinations of aliphatic primary amines and aliphatic secondary amines, as well as from sterically hindered aliphatic primary amines and aromatic primary amines. This breakthrough overcomes the previous limitation of using only aromatic amines and secondary amines for the selective synthesis of unsymmetrical ureas. Moreover, the method accommodates a wide range of substrates and demonstrates high tolerance to various functional groups, affording diverse unsymmetrical ureas with good to excellent yields and selectivity. Mechanistic investigations reveal that the high selectivity is due to two-stage temperature regulation, the selection of specific substrate structures and ratios, and the appropriate amount of COS. Additionally, the H₂S produced during the reaction is efficiently captured by the substrate or solvent, forming useful chemical products. This efficient synthetic methodology provides a mild and selective pathway for the preparation of unsymmetrical urea derivatives.