SN2 - Second-order Nucleophilic Substitution

Substrate Effects in $SN2$ Reactions

The rate of a reaction is frequently influenced to a significant degree by the spatial shape of the substrate. In $SN2$ reactions, the reaction rate depends considerably on the reaction center's degree of substitution. The influences on the reaction rate that arise from the substituent's spatial structure are called steric effects. Additionally, the reaction rate may be controlled by the substituent's ability to stabilize (delocalize) electrical charge (electronic effect).

Fig.1
Halogen exchange.
Tab.1
Relative reaction rates of halogen exchange.
Alkyl halideStructureClassRelative reaction rate
Methyl bromide $CH3Br$ Methyl 163
Ethyl bromide $CH3CH2Br$ Primary 1
Isopropyl bromide $(CH3)2CHBr$ Secondary 0.00074
tert-butyl bromide $(CH3)3CBr$ Tertiary negligible small

The cause of the reaction rate's large decrease in the halogen exchanges with different alkyl bromides is the increasing steric shielding of the central carbon. In an $SN2$ reaction, the nucleophile has to approach the central carbon from the side opposite to the leaving group (here: bromide). This approach is more sterically hindered the more alkyl substituents the central carbon carries. In the three-dimensional, interactive molecular models below, the steric effects of alkyl substituents are illustrated, in particular, when the spacefill presentation is activated.

Fig.2
Methyl bromide
Fig.3
Ethyl bromide
Fig.4
Isopropyl bromide
Fig.5
tert-Butyl bromide

Due to extremely low steric shielding by hydrogen atoms, methyl halides are particularly reactive in $SN2$ reactions. Primary substrates react considerably more rapidly than secondary and tertiary substrates do. In tert-butyl bromide, the reaction center is almost completely blocked by the three methyl substituents. Therefore, the $SN2$ reaction with tert-butyl bromide can only proceeds extremely slowly.

The connection between the reaction rate of $SN2$ reactions and the degree of substitution of the substrate's reaction center is depicted by the following illustration:

Fig.6
Connection between the reaction rate and the degree of substitution.

In connection with secondary and tertiary alkyl compounds, a competition between the $SN2$ reaction, on the one hand, and the $SN1$ reaction or elimination, on the other hand, is to be expected. Particularly in the case of tertiary alkyl compounds, the $SN2$ reaction is usually completely superseded by the $SN1$ reaction or elimination. In $SN1$ reactions and eliminations, the reaction rate is influenced to a much smaller degree by steric effects. The reaction rate is rather controlled by electronic effects. In other words, the more the reaction center's positive charge, which appears in the transition state, is stabilized by substituents, the higher the reaction rate is, as well. Therefore, in contrast to the $SN2$ reaction, the reaction rate of an $SN1$ reaction and an elimination usually increases with the reaction center's degree of substitution.

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