7.2 SN2 Reaction Mechanisms, Energy Diagram and Stereochemistry

S_N2 Reaction Mechanism

Let’s still take the reaction between CH₃Br and OH^– as an example of an S_N2 mechanism.

An S_N2 mechanism involves two electron pair transfers that occur at the same time; nucleophile attacking (red arrow) and leave group leaving (blue arrow). The nucleophile OH^– approaches the electrophilic carbon from the back side, the side that is opposite to the direction that the leaving group Br leaves. With the nucleophile OH^– getting closer, the Br starts to leave as well. The new C—OH bond formation and the old C—Br bond breaking occur at the same time. In a very short transient moment, the carbon atom is partially connected with both OH and Br, which gives the highest energy level state of the whole process called the transition state. In the transition state of an S_N2 reaction, there are five groups around the carbon and the carbon can be called “pentacoordinated”. As the OH^– continues to get closer to the carbon, the Br moves further away from it with the bonding electron pair. Eventually, the new bond is completely formed and the old bond is completely broken, which gives the product CH₃OH.

In the mechanism, the reaction proceeds in a single step that involves both the nucleophile and the substrate, so increasing the concentration of either increases the possibility of a collision, which explains the second-order kinetics of an S_N2 reaction. With both nucleophile attacking and leaving group leaving happen at the same time, S_N2 is also said to be a concerted mechanism, as concerted means simultaneous.

Energy Diagram of the S_N2 Mechanism

The energy changes for the above reaction can be represented in the energy diagram shown in Fig. 7.2b. S_N2 is a single-step reaction, so the diagram has only one curve. The products CH₃OH and Br^– are in lower energy than the reactants CH₃Br and OH^–, which indicates that the overall reaction is exothermic and the products are more stable.

The top of the curve corresponds to the transition state, which is the highest-energy structure involved in the reaction. A transition state always involves partial bonds, partially formed bonds and partially broken bonds, and therefore it is very unstable with no appreciable lifetime. The transition state therefore can never be isolated. The structure of the transition states is usually shown in a square bracket with a double-dagger superscript.

The Effect of Alkyl Halide Structure on S_N2 the Reaction Rate

For the discussions on the S_N2 mechanism so far, we focused on the reaction of methylbromide CH₃Br. Other alkyl halides could undergo S_N2 reactions as well. The studies on the reaction rate for S_N2 indicate that the structure category of electrophilic carbon in alkyl halide dramatically affects the reaction rate.

Table 7.1 Relative Reaction Rate of S_N2 for Different Types of Alkyl Halide

As shown in Table 7.1, methyl and primary halides are the substrates with the highest rate, the rate decreases a lot for secondary halides, and the tertiary halides do not undergo an S_N2 reaction at all because the rate is too low to be practical.

The relative reactivity of alkyl halides towards S_N2 reaction can therefore be summarized as:

Why is the trend like this? This can be explained by the mechanism of the S_N2 reaction. Actually, this is among the experimental evidence scientists used for proposing the mechanism. A key feature in the S_N2 mechanism is that the nucleophile attacks from the back side. When nucleophiles approach the carbon, it is easiest to get close to the methyl carbon because the hydrogen atoms connected to carbon are small in size. With the size of the groups connected to the carbon getting larger, it becomes more difficult to access the carbon, and such an approach is completely blocked for tertiary carbons with three bulky alkyl groups connected. Therefore, the reactivity difference is essentially caused by the steric effect. The steric effect is based on the steric size or volume of a group. Because of the steric hindrance of bulky groups on the electrophilic carbon, it is less accessible for nucleophiles to do back-side attacks, so the S_N2 reaction rate of secondary (2°) and tertiary (3°) substrates dramatically decreases. The 3° substrates never go with the S_N2 reaction mechanism because the reaction rate is too slow.

The Stereochemistry of S_N2 Reaction

Another feature of the S_N2 reaction mechanism is that the overall configuration of the carbon in the product gets inverted compared to that of the reactant, as an umbrella flipped inside out. Such inversion of the configuration is called Walden inversion. Let’s see what are the stereochemistry consequences for such inversion.

Start with the (R)-2-bromobutane. The S_N2 reaction produces only one enantiomer of the 2-butanol product, and it is predictable that the configuration of the product is supposed to be S because of the configuration inversion.

Answers to Chapter 7 Practice Questions