Theoretical Investigation into Rate-Determining Factors in Electrophilic Aromatic Halogenation

Abstract

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 Cl 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 Br 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.

Mechanism of Direct Electrophilic Aromatic Amination: an Electrophile is Found by Quantum‐Chemical Study

“…A comparison of the C−N distance in π‐complex, TS1, and σ‐complex shows that TS1 has a structure more similar to π‐complex. Thus, according to the Hammond postulate the direct amination has an earlier transition state than halogenations since halogenations show a closer structural similarity between the σ‐complex and corresponding transition state …”

“…The predicted ρ values and observed similarities allowed us to put amination of arenes by H 2 N 3 + somewhere close to nitration (Table ). As we stated above, amination is characterized by an earlier transition state than halogenations since TS1 in amination shows more similarity to the π‐complex, whereas TS in halogenations is more similar to the σ‐complex ,. Nitration was also shown to have an earlier transition state than halogenations .…”

Sulfonylation of Five‐Membered Aromatic Heterocycles Compounds through Nucleophilic Aromatic Substitution: Concerted or Stepwise Mechanism?

“…In 2018, they reported a theoretical investigation on the halogenation of mono‐substituted benzenes using Density Functional Theory (DFT) at PCM−M06‐2X/6‐311G(d,p) level. It was found that the reactions with Cl 2 and Br 2 procced by a stepwise mechanism, while the iodination with ICl involves a concerted mechanism …”

A Predictive Tool for Electrophilic Aromatic Substitutions Using Machine Learning

“…A more realistic mechanism can rationalize some of these observations by the formation of a π-complex, which can sometimes be rate-limiting but not selectivity-determining (Scheme ). , Furthermore, for some electrophiles such as iodine, the σ-complex may not be a true intermediate, but rather a transition state with a concerted deprotonation, detectable by a significant kinetic isotope effect . However, brominations and chlorinations seem to be reasonably well approximated by the schoolbook mechanism.…”