Theoretical Description of Substituent Effects in Electrophilic Aromatic Substitution Reactions

Abstract

AbstractThe ability of the current Kohn–Sham density functional theory (DFT) to compute the change of the proton affinity (PA) of phenol derivatives due to substitution is investigated. These systems can be used as models to predict reactivities in electrophilic aromatic substitution reactions. The complexity of the problem is increased systematically by introducing successively up to four substituents in five typical cases (methyl, cyano, fluorine, chlorine, and bromine). Our investigation can be regarded as representative for an important class of problems consistently encountered in the DFT modeling of organic reactions. High‐level theoretical reference data from CCSD(T) and SCS‐MP2 wave‐function calculations are presented, and the PAs are compared to those obtained by a series of density functionals (DFs). It is shown that not all DFs are capable of quantitatively reproducing the substituent effects. These can be simply linear in the number of substituents or show more complicated patterns. Especially for halogens, some DFs even fail completely. In these cases, linearly increasing errors with the number of groups are observed. Reliable results are obtained with hybrid DFs or the even more accurate double‐hybrid DF approach. The errors are attributed to the common self‐interaction (over‐delocalization) error in part of the DFs. Comparison with Hartree–Fock results shows that a reliable account of electron correlation is necessary to compute the PA of unsaturated and highly substituted molecules with chemical accuracy.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)