6.8:
SN2 Reaction: Mechanism
Kinetic studies of SN2 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 SN2 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 SN2 reaction mechanism being concerted where the nucleophile attacks from the backside while simultaneously displacing the leaving group and causing an inversion of configuration.
6.8:
SN2 Reaction: Mechanism
The kinetic studies of SN2 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. SN2 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 SN2 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:
- Brown, W.H., & Iverson, B.L., & Anslyn, V.E., & Foote S.C. (2014). Organic Chemistry. Mason, Ohio: Cengage Learning, 344-345.
- Solomons, G., & Fryhle, C. & Snyder, S. (2015). Organic Chemistry. New Jersey, NJ: Wiley, 246-248.
- Loudon, M., & Parise, J. (2016). Organic Chemistry. New York, NY: Macmillan Publishers, 391-393.
- Klein, D. (2017). Organic Chemistry. New Jersey, NJ: Wiley, 277-278.
- Clayden, J., & Greeves, N., & Warren, S. (2012). Organic Chemistry. Oxford: Oxford University Press, 340-342.