Electrophile affinity and positional selectivity in electrophilic substitution reactions of N-substituted pyrroles

Abstract

In terms of the density functional theory (DFT) using B3LYP/6-31G(d) method with full geometry optimization, gas-phase quantum chemical calculations were performed for σ-complexes formed upon the attack of electrophiles E (E = H+, Me+, Me3Si+, Br+, NO2 +, MeCO+, SO3) on α- and β-positions of furan, thiophene, selenophene, pyrrole, and N-substituted pyrroles (NR-pyrroles, R = Me, But, SiMe3, SiPri 3, C6H4NO2-p, SO2Ph, CHO, COOMe) and for respective α- and β-substituted electrophilic substitution products. The energy differences between the α- and β-isomers of the σ-complexes characterize the preferred direction of the electrophilic attack, while the energy differences between the isomeric products make it possible to estimate the energy preference of a particular product. An analysis of the results obtained demonstrates the effect of the structure of heterocycle, the nature of electrophile, and thermodynamic and steric factors on the positional selectivity (α/β ratio) in electrophilic substitution reactions of π-electron rich five-membered heteroaromatics.