DFT study of 1-, 4-, and 5-substituted 2-oxo-1,2,3,4-tetrahydropyrimidines: substituent steric and electronic effects, and ring flipping

Abstract

Steric and the electronic effects caused by the substituents in the 1-, 4-, and 5-positions of substituted 2-oxo-1,2,3,4-tetrahydropyrimidines were investigated using density functional theory at the B3LYP/6-31++G(d,p) level. Results of this study show that the heterocyclic ring adopts a pseudo-boat conformation, in which the C4 and N1 atoms are deviated from ring planarity. The C4-substituent occupies a pseudo-axial position and the space orientation of the substituent depends on the type and position of the additional substituent in this aryl group. The heights of the C4 and N1 atoms from the boat plane and the orientation of 5-CO moiety toward the heterocyclic ring depend on the electronic and steric effects of the substituents in the various positions. Ring flip calculations for 4-phenyl substituent explain the extreme steric effect caused by the substituent in the 1-position. These calculations indicate the more favored pseudo-axial orientation of the phenyl group over the equatorial orientation.