The relative favorability of placing substituents ortho or para in the cationic intermediate for electrophilic aromatic substitution

Abstract

AbstractRegioselectivity in electrophilic aromatic substitution (EAS) is partly governed by how well a preexisting substituent stabilizes or destabilizes the cationic intermediate formed by addition of an electrophile. Such intermediates were modeled computationally (G4) by adding a proton ortho, meta, or para to an existing substituent on a benzene ring. The effect of a meta substituent depends on the electronic character, as measured by the Hammett substituent constant σm or, better yet, σ+m. Similarly, the effect of a para or ortho substituent correlates with σ+p (= σ+). However, the influence of a substituent at the para position is 10% stronger than at the ortho position. Frontier molecular orbital arguments rationalize this observation. Consequently, the ortho:para product ratio in EAS is expected to depend, at least in part, on σ+p, with greater electron‐donating character associated with a greater preference for para over ortho. The ortho‐substituted cationic intermediate can even be favored over both meta and para if the electron‐withdrawing character is sufficient to favor ortho over para but insufficient to favor meta over either. This phenomenon is observed to occur in at least some cases when the quantity σ+p–σm falls between –0.5 and 0.