S_N2 Reaction: Mechanism

Kinetic studies of S_N2 reactions show that both the nucleophile and the substrate participate in the rate-determining step. However, they do not precisely explain how the molecules arrange during the reaction. To derive the full mechanism of an S_N2 reaction, consider the following theories.

Firstly, the substrate contains an electronegative halogen, which creates a polarized carbon-halide bond. This leads to an electrophilic center at the carbon attracting the nucleophile with its lone pair of electrons.

However, the presence of high electron density around the halide effectively blocks the frontside attack. Thus, the nucleophile approaches the electrophile from the side opposite to the leaving group leading to a backside attack.

As the nucleophile donates its lone pair to the electrophile, the leaving group pulls away with the electron pair bonded to the carbon. This results in a transition state where the bond formation between the nucleophile and substrate and the bond breakage between the substrate and leaving group occur simultaneously.

The transition state is highly unstable. To regain stability, the leaving group departs with the electron pair in a concerted manner leading to inversion of the substrate configuration.

Molecular orbital theory further supports the backside attack. The nucleophile’s lone pair of electrons occupies the highest molecular orbital, or HOMO. To form a bond, the HOMO needs to overlap with the lowest unoccupied molecular orbital, or LUMO, of the electrophile.

When a nucleophile approaches the electrophile from the same side as the leaving group, it faces a node, which results in the HOMO overlapping with the bonding and antibonding LUMO. Yet, no bond forms as the antibonding overlap cancels the bonding overlap.

In contrast, the backside approach of the nucleophile efficiently overlaps the HOMO with the LUMO of the electrophile leading to bond formation.

Thus, both theories support the S_N2 reaction mechanism being concerted where the nucleophile attacks from the backside while simultaneously displacing the leaving group and causing an inversion of configuration.