6.8 : S_N2 Reaction: Mechanism

The kinetic studies of S_N2 reactions suggest an essential feature of its mechanism: it is a single-step process without intermediates. Here, both the nucleophile and the substrate participate in the rate-determining step.

The presence of the more electronegative halogen in the substrate creates a polarized carbon-halide bond. The halide pulls the electron cloud generating an electrophilic center at the carbon atom. Thus, the carbon atom carries a partial positive charge while the halide has a partial negative charge. The electrophilic carbon attracts the nucleophile with its lone pair of electrons.

However, the high electron density around the halide effectively blocks the same-side attack by the nucleophile. Thus, the nucleophile approaches the electrophile from the substrate's electron-poor side, leading to a back-sided attack. Therefore, the nucleophile donates its lone pair to the electrophilic carbon, 180° away from the leaving group.

As the halide departs from the electrophilic carbon, it moves away with the electron pair bonded to the carbon. This results in a transition state with a partially formed bond between the nucleophile and substrate and a partially broken bond between the substrate and leaving group.

With three solid and two partial bonds at the carbon, the transition state is highly unstable. Thus, the leaving group departs with the electron pair bonded to the carbon, leading to inversion of substrate configuration. (Figure 1)

Figure 1. S_N2 mechanism

Further, the molecular orbital theory supports the backside attack as well. When the bonding orbital of the nucleophile, i.e., the highest occupied molecular orbital, or HOMO, approaches the lowest unoccupied molecular orbital, or LUMO, of the substrate from the same side as the leaving group, it faces a node canceling both the bonding and the anti-bonding overlap. In contrast, a backside attack by the nucleophile efficiently overlaps with the substrate's LUMO, resulting in bond formation.

Thus, the S_N2 mechanism occurs in a single step, when the incoming nucleophile reacts with the substrate from a direction opposite the leaving group, which is displaced.

Suggested reading:

1. Brown, W.H., & Iverson, B.L., & Anslyn, V.E., & Foote S.C. (2014). Organic Chemistry. Mason, Ohio: Cengage Learning, 344-345.
2. Solomons, G., & Fryhle, C. & Snyder, S. (2015). Organic Chemistry. New Jersey, NJ: Wiley, 246-248.
3. Loudon, M., & Parise, J. (2016). Organic Chemistry. New York, NY: Macmillan Publishers, 391-393.
4. Klein, D. (2017). Organic Chemistry. New Jersey, NJ: Wiley, 277-278.
5. Clayden, J., & Greeves, N., & Warren, S. (2012). Organic Chemistry. Oxford: Oxford University Press, 340-342.