The suppressed reactivity of pyridine towards electrophiles as a result of an interplay between intra- and intermolecular interactions

A new accounting is suggested for the suppressed relative reactivity of all carbon atoms of pyridine as compared to benzene in the bimolecular electrophilic substitution (S_E2) processes in terms of an interplay between intra- and intermolecular interactions. Introduction of a nitrogen atom is shown to be accompanied by emergence of intramolecular interactions between the usual molecular orbitals of benzene that, in turn, give birth to definite mixed terms containing products of intra- and intermolecular interactions in the perturbative expansions for populations transferred between orbitals of the aromatic ring and those of electrophile. For ortho and para directions of the electrophilic attack, all the principal intramolecular interactions are shown to yield negative contributions to the intermolecular charge transfer in accordance with the dramatically reduced reactivities of these positions in pyridine. By contrast, contributions of different signs are shown to emerge in the relevant expressions referring to the meta attack. In this connection, conditions are revealed and analyzed that ensure the reduced intermolecular charge transfer for the meta position as well. Electrophiles of sufficiently high electron-accepting ability are shown to meet these conditions.