Solvent and Autocatalytic Effects on the Stabilisation of the σ‐Complex during Electrophilic Aromatic Chlorination

Abstract

The solvent and autocatalytic effects of the electrophilic aromatic chlorination of benzene are studied using a combined approach of static calculations and ab initio metadynamics simulations. Different possible reaction pathways are investigated and the influence of the solvents (CCl , acetonitrile and acetic acid) is thoroughly assessed. Our results show that the stability and lifetime of a charged σ-complex is increased by electrostatic stabilisation effects of the environment, which can originate from catalytic HCl, solvating effects of polar solvents (acetonitrile), or specific hydrogen bonding interactions with the solvent (acetic acid). Metadynamics simulations reveal a new chlorine addition mechanism explaining the autocatalytic effects of the reaction. The strength of combining static calculations and metadynamics simulations is highlighted, which provide complementary insight into chemical reactions in solvent.

A dynamic picture of the halolactonization reaction through a combination of ab initio metadynamics and experimental investigations

“…[51][52][53][54] Recently, we have shown the usefulness of rst-principles metadynamics (MtD) simulations to study the mechanisms of the electrophilic aromatic sulfonation and chlorination, with a focus on the formation of ionic intermediates during the reaction. 55,56 In this work, a similar approach will be used to revisit the mechanism of the non-catalysed halolactonization. Emphasis will be put on the formation of a possible ionic intermediate, which differentiates the NAAA mechanism from the classic two-step mechanism.…”

SuFEx-Enabled, Chemoselective Synthesis of Triflates, Triflamides and Triflimidates

“…We, among others, have previously shown the ability of AIMtD to elucidate reaction mechanisms, quantify reaction barriers and unveil solvation effects. [44] Figure 1. (A) Transition states obtained through metadynamics simulations for: I) the non-activated CF3SO2F -triflylation of piperidine in acetonitrile, II) the DMAPactivated CF3SO2F-triflylation of piperidine in acetonitrile, III) the Et3N-activated CF3SO2F-triflylation of piperidine in acetonitrile and IV) the non-activated CF3SO2Ftriflylation of piperidine in acetonitrile including two molecules of piperidine.…”

“…We, among others, have previously shown the ability of AIMtD to elucidate reaction mechanisms, quantify reaction barriers and unveil solvation effects. [44] Here, piperidine served as a case study for the computationally modeled CF3SO2F triflylation reaction (Figure 1A). In parallel, a series of experimental studies was performed, to complement the in silico findings (Figure 1B).…”

An analysis of electrophilic aromatic substitution: a “complex approach”

“…It can be seen from Scheme 5 that the EAS reaction also goes through the formation of p-complexes and s-complexes, [16][17][18][19][20][21][22][23] which explains the gradual destabilization of the aromatic system. First, a p-complex is formed, which is thermodynamically less stable and rapidly isomerizes to the corresponding scomplex.…”

“…5a Deformation of such a HOMO leads to the formation of a C(sp3) site, as already mentioned, while the C(sp 2 )-E bond is shortened relative to the same bond in the p-complex. 20 Fig. 4 shows the ratio of the angles that overlap the electrophile and the hydrogen atom, with respect to the plane axis (i.e., the benzene nucleus).…”