Predicting S_N1 vs. S_N2 mechanisms; competition between nucleophilic substitution and elimination reactions

When considering whether a nucleophilic substitution is likely to occur via an S_N1 or S_N2 mechanism, we really need to consider three factors:

1) The electrophile: when the leaving group is attached to a methyl group or a primary carbon, an S_N2 mechanism is favored (here the electrophile is unhindered by surrounded groups, and any carbocation intermediate would be high-energy and thus unlikely). When the leaving group is attached to a tertiary, allylic, or benzylic carbon, a carbocation intermediate will be relatively stable and thus an S_N1 mechanism is favored.

2) The nucleophile: powerful nucleophiles, especially those with negative charges, favor the S_N2 mechanism. Weaker nucleophiles such as water or alcohols favor the S_N1 mechanism.

3) The solvent: Polar aprotic solvents favor the S_N2 mechanism by enhancing the reactivity of the nucleophile. Polar protic solvents favor the S_N1 mechanism by stabilizing the carbocation intermediate. S_N1 reactions are frequently solvolysis reactions.

For example, the reaction below has a tertiary alkyl bromide as the electrophile, a weak nucleophile, and a polar protic solvent (we’ll assume that methanol is the solvent). Thus we’d confidently predict an S_N1 reaction mechanism. Because substitution occurs at a chiral carbon, we can also predict that the reaction will proceed with racemization.

In the reaction below, on the other hand, the electrophile is a secondary alkyl bromide – with these, both S_N1 and S_N2 mechanisms are possible, depending on the nucleophile and the solvent. In this example, the nucleophile (a thiolate anion) is strong, and a polar aprotic solvent is used – so the S_N2 mechanism is heavily favored. The reaction is expected to proceed with inversion of configuration.