Electrophilic Aromatic Substitution: New Insights into an Old Class of Reactions

ConspectusThe classic SEAr mechanism of electrophilic aromatic substitution (EAS) reactions described in textbooks, monographs, and reviews comprises the obligatory formation of arenium ion intermediates (σ complexes) in a two-stage process. Our findings from several studies of EAS reactions challenge the generality of this mechanistic paradigm. This Account focuses on recent computational and experimental results for three types of EAS reactions: halogenation with molecular chlorine and bromine, nitration by mixed acid (mixture of nitric and sulfuric acids), and sulfonation with SO3. Our combined computational and experimental investigation of the chlorination of anisole with molecular chlorine in CCl4 found that addition–elimination pathways compete with the direct substitution processes. Detailed NMR investigation of the course of experimental anisole chlorination at varying temperatures revealed the formation of addition byproducts. Moreover, in the absence of Lewis acid catalysis, the direct halogena...