7.8     Summary and Overview of the S_N2 and S_N1 Reactions

These two substitution reactions are interconnected by more than the ultimate formation of a substitution product. They complement each other—when one is ineffective, the other is likely to work well. For example, the S_N2 reaction works best for methyl and primary substrates, which is exactly when the S_N1 reaction is least effective. When the S_N2 reaction fails, as with tertiary substrates, the S_N1 reaction is most effective (Fig. 7.82).

 

At the extremes, the situation is clear. The S_N2 reaction dominates for methyl and primary substrates because there is little steric hindrance to the displacement of the leaving group and because the competing S_N1 reaction is disfavored by the necessity of forming the highly unstable methyl or primary carbocations (Fig. 7.83).

 

The S_N1 reaction dominates for tertiary substrates because ionization can produce the relatively stable tertiary carbocation and because the competing S_N2 reaction is strongly disfavored by the steric hindrance to the nucleophile approaching from the rear (Fig. 7.84).

 

In the middle ground—secondary substrates—we might expect to be able to find both reactions. Small R groups, use of a powerful nucleophile, and a solvent of proper polarity for the charge type of the reaction favor the S_N2 reaction. Large R groups, a weak nucleophile, and a polar solvent favor the S_N1 reaction (Fig. 7.85).

We have given a picture of these reactions that emphasizes extremes, developing an “either S_N2 or S_N1” view. However, the situation is messier than this simple explanation would suggest, especially for secondary compounds. Imagine beginning to ionize a bond to a leaving group. As the bond stretches, positive charge begins to develop on carbon (δ⁺), and rehybridization toward sp² begins as the groups attached to the carbon flatten out (Fig. 7.86).

 

If we simply continue the process of ionization, we have the pure S_N1 reaction. If we let a nucleophilic solvent molecule interact with the rear of the departing bond and ultimately form a bond to carbon, we have the S_N2 reaction with inversion (Fig. 7.87).

 

How strong an interaction with the rear lobe of the orbital is needed before we call it bonding? In polar solvents, ions are highly solvated, and in an S_N1 reaction solvation will begin to be important as soon as a δ⁺ charge begins to build up on carbon. Solvation will be especially easy at the rear of the departing group as the leaving group shields the front side. We have already seen that the leaving group can hinder reaction at one side of the developing cation and produce some net inversion in the reaction (Figs. 7.76 and 7.77).

Now we begin to see the difficulty of telling the two mechanisms apart in some situations. When does “preferential solvation from the rear” become “displacement from the rear”? It becomes painfully hard to sort out in some cases. Organic chemistry is frustratingly, if delightfully, messy.

This messiness raises its head in other ways. Almost all substitution reactions are accompanied by some formation of alkene. In organic chemistry, few reactions proceed in 100% yield, quantitatively producing one molecule from another. A large part of the business of organic synthesis is the search for specificity. Synthetic chemists seek reagents and reaction conditions that greatly favor one reaction pathway over others. In particular, attempts to synthesize molecules through substitution reactions must take account of competitive reactions called eliminations. A hydrogen atom and a leaving group are lost (eliminated) from the substrate to give an alkene (Fig. 7.88). In the next chapter, we examine two general mechanisms for these elimination reactions.