Urea hydrogen-bond donor strengths: bigger is not always better†‡

Abstract

The hydrogen-bond donor strength of ureas, widely used in hydrogen-bond donor catalysis, molecular recognition, and self-assembly, can be enhanced by increasing the size of the chalcogen X in the CX bond from O to S to Se and by introducing more electron-withdrawing substituents because both modifications increase the positive charge on the NH groups which become better hydrogen-bond donors. However, in 1,3-diaryl X-ureas, a steric mechanism disrupts the positive additivity of these two tuning factors, as revealed by our quantum-chemical analyses. This leads to an enhanced hydrogen-bond donor strength, despite a lower NH acidity, for 1,3-diaryl substituted O-ureas compared to the S- and Se-urea analogs. In addition, we provide a strategy to overcome this steric limitation using a predistorted urea-type hydrogen-bond donor featuring group 14 elements in the CX bond so that the hydrogen-bond donor strength of X-urea derivatives bearing two aryl substituents can be enhanced upon varying X down group 14.