The SN2 reaction: Substitution Nucleophilic Bimolecular

Several distinct mechanisms are possible for nucleophilic substitution reactions at saturated C atoms, depending on the substrate, nucleophile, leaving group and the reaction conditions. By far the most common are the S_N1 and S_N2 mechanisms.

Simple alkyl groups, methyl and primary alkyl groups always react by the S_N2 mechanism and never by S_N1.

Why methyl and primary alkyl groups react by the S_N2 mechanism? What are the steps in an S_N2 mechanism?

Partly because the corresponding cations are unstable and partly because it is easy for the nucleophile to attack the C atom since it is surrounded by H atoms – and not by bulky alkyl groups.

Experimental results show the following in S_N2 reactions:

In this mechanism (Fig. 1)  there is backside attack¹. The nucleophile attacks the carbon atom on the opposite side from the leaving group – 180 away from the leaving group – and the carbon atom turns inside out as the reaction proceeds

The reaction is a one-step process with no intermediate

The C-Nu bond is formed (where Nu nucleophile) as the C-X bond is broken (where X the leaving group) to generate transition state 1.

If the C atom under attack is a stereogenic center the result will be inversion of configuration

The kinetics of the rection is 2^nd order

There is absence of rearrangement (absence of intermediate carbocations)

The rate of reaction decreases in the order: -CH3 > 1^o > 2^o > 3^o

Fig. 1: Mechanism for the S_N2 reaction

The energy necessary to break the C-X bond is supplied by the simultaneous formation of the C-Nu bond. The transition state 1 is shown in Fig.1

The group X must leave as the group Nu comes in because the carbon atom cannot have more than eight electrons in its outer shell. At the transition state, the central C atom has an sp2 hybridization with an approximately perpendicular p orbital. One lobe of this p orbital overlaps with the nucleophile and the other with the leaving group. This is why a backside attack always occurs in S_N2 reactions because in a hypothetical front-side attack both the nucleophile Nu and the leaving group X would have to overlap with the same lobe of the p orbital.

During the transition state the three non-reacting substituents and the central carbon are on the same plane.

There is a large amount of evidence for the S_N2 mechanism:

• Kinetic evidence

• Stereochemical evidence

Kinetic evidence

Since both the nucleophile and the substrate are involved in the rate-determining step , the reaction should be first order in each component, second order overall.

The rate expression for S_N2 reactions has been found to be:

Rate = k * [nucleophile] * [substrate] = k * [Nu] * [RX]

This rate law has been found to apply. The 2 in S_N2 reactions stands for bimolecular.

References

1. L. Sun et al., J.A.C.S., 123, 5753 (2001)

2. R. Bruckner, “Advanced Organic Chemistry – Reaction Mechanisms”, 2^nd Edition, Elsevier, 2002

3. M.B. Smith & J. March “March’s Advanced Organic Chemistry”, 6^th Edition, Wiley-Interscience, 2007