Nucleophilic substitution

In chemistry, nucleophilic substitution is a class of substitution reaction in which a electron-rich nucleophile attacks a molecule and replaces a group or atom, called the leaving group. It is a fundamental class of reaction in organic chemistry, where the reaction occurs at a carbon centre, but nucleophilic substitutions are also well known in inorganic covalent compounds too.

Nucleophilic substitution at saturated carbon centres{{Ref|4}}

S_N1 and S_N2 reactions

In 1935, Edward D. Hughes and Sir Christopher Ingold studied nucleophilic substitution reactions of alkyl halides and related compounds. They proposed a theory proposing that there were two main mechanisms at work, both of them competing with each other. The two main mechanisms are the SN1 reaction and the SN2 reaction. S stands for chemical substitution, N stands for nucleophilic, and the number represents the kinetic order of the reaction.

Related Topics:
Edward D. Hughes - Sir Christopher Ingold - Alkyl halide - S_N1 reaction - S_N2 reaction - Kinetic order

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In the SN2 reaction, the addition of the nucleophile and the elimination of leaving group take place simultaneously. SN2 occurs where the central carbon atom is easily accessible to the nucleophile. By contrast the SN1 reaction involves two steps. SN1 reactions tend to be important when the central carbon atom of the substrate is surrounded by bulky groups, both because such groups interfere sterically with the SN2 reaction (discussed above) and because a highly substituted carbon forms a stable carbocation.

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Initially, the rate of the nucleophilic substitution was a little puzzling as the rate followed the pattern :

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CH3X > primary > secondary < tertiary

Related Topics:
Primary - Secondary - Tertiary

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The reaction kinetics changed from second order to first order.

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The SN1 and SN2 reactions are influenced by different factors

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SN1 reactivity rates follow the trend CH3X < primary < secondary < tertiary

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SN2 reactivity rates follow the trend CH3X > primary > secondary > tertiary

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The total reactivity is the sum of the two rates.

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A graph showing the relative reactivities of the different alkyl halides towards SN1 and SN2 reactions. Also see Table 1.

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There are many reactions in organic chemistry that involve this type of mechanism. Common examples include

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• organic reductions with hydrides, for example

:: R-X → R-H using LiAlH4   (SN2)

Related Topics:
R-X - R-H - LiAlH₄

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• hydrolysis reactions such as

:: R-Br + OH− → R-OH + Br− (SN2) or

Related Topics:
R-OH - Br⁻

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:: R-Br + H2O → R-OH + HBr   (SN1)

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• Williamson ether synthesis

:: R-Br + OR'− → R-OR' + Br−   (SN2)

Related Topics:
OR'⁻ - R-OR'

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Other mechanisms

Besides SN1 and SN2, other mechanisms are known, although they are less common. The SNi mechanism is observed in reactions of thionyl chloride with alcohols, and it is similar to SN1 except that the nucleophile is delivered from the same side as the leaving group.

Related Topics:
SNi - Thionyl chloride - Alcohol

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Nucleophilic substitutions can be accompanied by an allylic rearrangement as seen in reactions such as the Ferrier rearrangement. This type of mechanism is called an SN1' or SN2' reaction (depending on the kinetics). With allylic halides or sulfonates, for example, the nucleophile may attack at the γ unsaturated carbon in place of the carbon bearing the leaving group. This may be seen in the reaction of 1-chloro-2-butene with sodium hydroxide to give a mixture of 2-buten-1-ol and 1-buten-3-ol:

Related Topics:
Allylic rearrangement - Ferrier rearrangement - Allylic - Sodium hydroxide

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:CH3CH=CH-CH2-Cl → CH3CH=CH-CH2-OH + CH3CH(OH)-CH=CH2

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