Diminished Reactivity of Ortho-Substituted Phenacyl Bromides toward Nucleophilic Displacement

A systematic increase of substitution rates by tert-butylamine on α-bromopropiophenones is observed with meta or para substituents with increasing electron-withdrawing ability (k × 10³ L M^-1 min^-1 = 12.7 (p-CH₃), 15.7 (o-F), 20.5 (H), 20.0 (p-Cl), 23.6 (m-Cl), 27.3 (p-CF₃)). Within an ortho-substituted series, the reactivities decrease (k × 10³ L M^-1 min^-1 = 7.64 (o-OCH₃), 5.31 (o-CH₃), 2.85 (o-Cl), 2.40 ( o-CF₃)). Ortho-substitution results occur from rotational barrier effects and an Aδ_σ⁺ Bδ_σ⁺ repulsion. The major bonding contribution between reaction and α-substituent centers (A−B) is only the σ bond. When π bonding is allowed between A and B (meta/para-substitution), delocalization and stabilization of the reacting center occurs.