Traceless synthesis of hydantoin by focused microwave irradiation

An efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 1,3-disubstituted hydantoin has been developed. Chloroacetyl chloride was directly anchored to HO–PEG–OH and subsequently reacted with various primary amines in a microwave cavity. The PEG bound secondary amine coupled with isocyanates and concomitant cyclization–cleavage step occurred in mild basic conditions by microwave flash heating. The desired products were then liberated from the soluble matrix in modest yield and high purity.