Towards physical interpretation of substituent effects: the case of N- and C3-substituted pyrrole derivatives

Abstract

Classical and reverse substituent effects were studied for pyrrole derivatives. Two extensive sets of pyrrole derivatives with NO, NO2, CN, CF3, COMe, COOH, CHO, CONH2, Cl, SH, SiH3, F, PH2, H, Me, OMe, OH, NH2, NHMe, NMe2, Li, BeH, BH2, Na, MgH, and AlH2 substituents at N and C3 positions were taken into account. Analysis of the substituent effects was based on charges of the Substituent Active Region (cSAR). The cSAR values were obtained from atomic charges calculated within the Quantum Theory of Atoms in Molecules (QTAIM) methodology. Calculations were performed at the B3LYP/6-311++G** level of theory. It was documented that classical substituent effect in substituted pyrroles is much greater (approximately ten times) for substituents at C3 position than at NH group. The reverse substituent effect is also greater in C3-substituted pyrroles that in N-substituted ones. As a result of observed correlations, substituent constants for some rare substituents such as Li, BeH, BH2, Na, MgH, and AlH2 were evaluated.