Theoretical Investigation into Rate-Determining Factors in Electrophilic Aromatic Halogenation.

The halogenation of monosubstituted benzenes in aqueous solvent was studied using density functional theory at the PCM-M06-2 X/6-311G(d,p) level. The reaction with Cl2 begins with the formation of C atom coordinated π-complex and is followed by the formation of the σ-complex, which is rate-determining. The final part proceeds via the abstraction of the proton by a water molecule or a weak base. We evaluated the use of the σ-complex as a model for the rate-determining transition state (TS) and found that this model is more accurate the later the TS comes along the reaction coordinate. This explains the higher accuracy of the model for halogenations (late TS) compared to nitrations (early TS); that is, the more deactivated the substrate the later the TS. The halogenation with Br2 proceeds with a similar mechanism as the corresponding chlorination, but the bromination has a very late rate-determining TS that is similar to the σ-complex in energy. The iodination with ICl follows a different mechanism than chlorination and bromination. After the formation of the π-complex, the reaction proceeds in a concerted manner without a σ-complex. This reaction has a large primary hydrogen kinetic isotope effect in agreement with experimental observations.