7.4 The SN1 Reaction

Most nucleophilic substitutions take place by the S_N2 pathway just discussed. The reaction is favored when carried out with an unhindered substrate and a negatively charged nucleophile in a polar aprotic solvent, but is disfavored when carried out with a hindered substrate and a neutral nucleophile in a protic solvent. You might therefore expect the reaction of a tertiary substrate (hindered) with water (neutral, protic) to be among the slowest of substitution reactions. Remarkably, however, the opposite is true. The reaction of the tertiary halide 2-bromo-2-methylpropane (CH₃)₃CBr with H₂O to give the alcohol 2-methyl-2-propanol is more than 1 million times faster than the corresponding reaction of CH₃Br to give methanol.

What’s going on here? A nucleophilic substitution reaction is occurring—a hydroxyl group is replacing a halogen—yet the reactivity order seems backward. These reactions can’t be taking place by the S_N2 mechanism we’ve been discussing, so we must therefore conclude that they are occurring by an alternative substitution mechanism. This alternative mechanism is called the S_N1 reaction, for substitution, nucleophilic, unimolecular.

In contrast to the S_N2 reaction of CH₃Br with OH^–, the S_N1 reaction of (CH₃)₃CBr with H₂O has a rate that depends only on the alkyl halide concentration and is independent of the H₂O concentration. In other words, the process is a first-order reaction; the concentration of the nucleophile does not appear in the rate equation.

To explain this result, we need to know more about kinetics measurements. Many organic reactions occur in several steps, one of which usually has a higher-energy transition state than the others and is therefore slower. We call this step with the highest transition-state energy the rate-limiting step, or rate-determining step. No reaction can proceed faster than its rate-limiting step, which acts as a kind of traffic jam, or bottleneck. In the S_N1 reaction of (CH₃)₃CBr with H₂O, the fact that the nucleophile concentration does not appear in the first-order rate equation means that it is not involved in the rate-limiting step and must therefore be involved in some other, non-rate-limiting step. The mechanism shown in Figure 7.6 accounts for these observations.

Figure 7.6 MECHANISM: The mechanism of the S_N1 reaction of 2-bromo-2-methylpropane with H₂O involves three steps. Step 1—the spontaneous, unimolecular dissociation of the alkyl bromide to yield a carbocation—is rate-limiting.

Unlike what occurs in an S_N2 reaction, where the leaving group is displaced while the incoming nucleophile approaches, an S_N1 reaction takes place by loss of the leaving group before the nucleophile approaches.

Because an S_N1 reaction occurs through a carbocation intermediate, its stereochemical outcome is different from that of an S_N2 reaction. Carbocations, as we’ve seen, are planar, sp²-hybridized, and achiral. Thus, if we carry out an S_N1 reaction on one enantiomer of a chiral reactant and go through an achiral carbocation intermediate, the product loses its optical activity. That is, the symmetrical intermediate carbocation can react with a nucleophile equally well from either side, leading to a racemic, 50 : 50 mixture of enantiomers (Figure 7.7).

Figure 7.7 Stereochemistry of the S_N1 reaction. Because the reaction goes through an achiral intermediate, an enantiomerically pure reactant gives an optically inactive racemic product.

Problem 7.7
What product(s) would you expect from reaction of (S)-3-chloro-3-methyloctane with acetic acid? Show the stereochemistry of both reactant and product.

Problem 7.8
Assign configuration to the following substrate, and show the stereochemistry and identity of the product you would obtain by S_N1 reaction with water (reddish brown = Br):