A molecular electron density theory study of the bimolecular nucleophilic substitution reactions on monosubstituted methyl compounds†

The nucleophilic substitution reactions involving methyl monosubstituted compounds have been studied within the Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311+G(d,p) computational level in DMSO. This study aims to characterize the electronic nature of the transition state structures (TSs) involved in the so-called S_N2 and S_Ni reactions. Both electron localization function and atom-in-molecules topological analyses indicate that the TSs involved in these nucleophilic substitutions can be described as a central methyl CH₃⁺ carbocation, which is strongly stabilized by the presence of two neighbouring nucleophilic species through electron density transfer. This MEDT study establishes a significant electronic similarity between the so-called S_N1 and S_N2 reactions. Due to the weak electrophilic character of the methyl tetrahedral carbons, the departure of the leaving group should be expected with the approach of the nucleophile. However, while along the S_N1 reactions, the strong stabilization of the tertiary carbocation does not demand the participation of the nucleophile, along the S_N2 and S_Ni reactions involving primary tetrahedral carbons, the nucleophiles should participate in the reaction to stabilize the unstable methyl carbocation.