Predicting S N 1 vs. S N 2 mechanisms; competition between nucleophilic substitution and elimination reactions When considering whether a nucleophilic substitution is likely to occur via an S N 1 or S N 2 mechanism, we really need to consider three factors: The electrophile: when the leaving group is attached to a methyl group or a primary carbon, an S N 2 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 N 1 mechanism is favored. The nucleophile : powerful nucleophiles, especially those with negative charges, favor the S N 2 mechanism. Weaker nucleophiles such as water or alcohols favor the S N 1 mechanism. The solvent : Polar aprotic solvents favor the S N 2 mechanism by enhancing the reactivity of the nucleophile. Polar protic solvents favor the S N 1 mechanism by stabilizing the carbocation intermediate. S N 1 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 N 1 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 N 1 and S N 2 mechanisms are possible, depending on the nucleophile and the solvent. In this example, the nucleophile (a thiolate anion) is strong, and a polar protic solvent is used – so the S N 2 mechanism is heavily favored. The reaction is expected to proceed with inversion of configuration. Example 7.17.1 Determine whether each substitution reaction shown below is likely to proceed by an S N 1 or S N 2 mechanism. Solution Contributors Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)