Regioselectivity in Electrophilic Aromatic Substitution: Insights from Interaction Energy Decomposition Potentials

Abstract The SEAr reaction was scrutinized using a quantitative, fragment‐based interaction energy decomposition analysis (EDA) as implemented in the ADF program. The interaction energy between monosubstituted benzene derivatives and a model electrophile at the onset of the reaction was studied and decomposed into Pauli repulsion, electrostatic interaction and orbital interaction terms for a plane parallel to the molecular plane. As such experimentally observed selectivity patterns arise in the orbital interaction, stressing again the role of both electrophile and benzene derivative in determining the regioselectivity. Using the HSAB principle and MO theory, the orientation mechanism of the SEAr is further explored.