SN2 - Second-order Nucleophilic Substitution

Influences on the $SN2$ Reaction

The course of an $SN2$ reaction is mainly influenced by the following parameters:

• The substrate structure.
• The nature of the nucleophile.
• The leaving group's character.
• The solvent.

Influence of the substrate structure on the $SN2$ reaction

Tab.1
Reaction rates of some substitutions of bromine by iodine in different alkyl bromides (bromoalkanes).
SubstituentAlkyl bromideRelative reaction rate
Methyl $CH3Br$ 145
Primary $CH3CH2Br$ 1
Secondary $(CH3)2CHBr$ 0.0078
Tertiary $(CH3)3CBr$ negligible small

Steric hindrance in the substrate increases the transition state's energy. As a result, the activation energy rises, while the reaction rate is reduced. Methyl compounds are particularly reactive in $SN2$ reactions. The reaction rate of $SN2$ reactions with primary alkyl compounds is considerably higher than that of $SN2$ reactions with secondary and tertiary alykl compounds. In addition, in the cases of secondary and tertiary alykl compounds, an $SN2$ reaction is largely superseded by an $SN1$ reaction or .

Influence of the nucleophile on the $SN2$ reaction

Good nucleophiles are less stable than poor nucleophiles. Thus, they have a higher energy in the ground state. As a result, the activation energy in an $SN2$ reaction is lower and the reaction rate is consequently higher than in an $SN2$ reaction with a comparatively stable nucleophile. Basic, negatively charged nucleophiles are more reactive than uncharged nucleophiles. Small nucleophiles react more rapidly than sterically-demanding nucleophiles.

Fig.1

Influence of the leaving group on the $SN2$ reaction

Fig.2
Average relative reaction rates of some leaving groups in $SN2$ reactions.

Stable anions are good leaving groups. If the leaving group is a stable anion, the transition state's energy is lower than with a leaving group that is a less stable anion. Consequently, the activation energy is lower, and the reaction rate is higher. The larger the area in which the negative charge is located is, or the more delocalized the negative charge is, the more stable anions are. Therefore, iodide anions, for instance, are better leaving groups than chloride anions are. On a laboratory-scale and large-scale, tosylates and mesylates are often applied to organic syntheses. In the transition state, their partial negative charge is particularly well delocalized, so that the transition state's energy is considerably low. Fluoride anions, hydroxide anions, alkoxides, and amide anions are poor leaving groups. Therefore, $SN2$ reactions with fluoroalkanes, alcohols, ethers, or amines virtually never occur. However, acid-catalysed $SN2$ reactions with alcohols or amines can take place, as the leaving group does not consist of the hydroxide anion, but water, while ammonia functions in place of the amide anion, as well.

Influence of the solvent on the $SN2$ reaction

In protic solvents, such as water and alcohols, the nucleophile is more stabilized by solvation than the transition state is. As a result, the nucleophile's ground state energy is reduced to a higher degree than the transition state's energy is. This leads to a higher activation energy and thus to a lower reaction rate. In polar aprotic solvents, the nucleophile is less solvated - and thus less stabilized in the ground state - than it is in polar protic solvents. Consequently, the nucleophile is more reactive, the activation energy is lower, and the reaction rate is higher. Examples of polar aprotic solvents are DMSO, DMF and HMPT (hexamethylphosphoric triamide). HMPT is particularly effective in $SN2$ reactions. However, it is considerably toxic.

Fig.3
Polar aprotic solvents.

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