Everything about Nucleophilic Substitution totally explained
In
organic and
inorganic chemistry,
nucleophilic substitution is a fundamental class of
substitution reaction in which an "electron rich"
nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom
attached to a group or atom called the
leaving group; the positive or partially positive atom is referred to as an
electrophile.
The most general form for the reaction may be given as
» Nuc
: + R-LG → R-Nuc + LG
:
The electron pair (
:) from the nucleophile (Nuc) attacks the substrate (R-LG) forming a new bond, while the leaving group (LG) departs with an electron pair. The principal product in this case is R-Nuc. The nucleophile may be electrically neutral or negatively charged, whereas the substrate is typically neutral or positively charged.
An example of nucleophilic substitution is the
hydrolysis of an
alkyl bromide,
R-Br, under alkaline conditions, where the
attacking nucleophile is the
OH− and the
leaving group is
Br-.
» R-Br + OH
− → R-OH + Br
−
Nucleophilic substitution reactions are commonplace in organic chemistry, and they can be broadly categorised as taking place at an
aliphatic (
saturated) carbon or at (less often) an
aromatic or other unsaturated carbon centre.
Nucleophilic substitution at saturated carbon centres
SN1 and SN2 reactions
In 1935,
Edward D. Hughes and
Sir Christopher Ingold studied nucleophilic substitution reactions of
alkyl halides and related compounds. They proposed 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.
In the S
N2 reaction, the addition of the nucleophile and the elimination of leaving group take place simultaneously. S
N2 occurs where the central carbon atom is easily accessible to the nucleophile. By contrast the S
N1 reaction involves two steps. S
N1 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 S
N2 reaction (discussed above) and because a highly substituted carbon forms a stable
carbocation.
Initially, the rate of the nucleophilic substitution was a little puzzling as the rate followed the pattern :
CH
3X > primary >
secondary <
tertiary
The
reaction kinetics changed from second order to first order.
The S
N1 and S
N2 reactions are influenced by different factors
S
N1 reactivity rates follow the trend CH
3X < primary < secondary < tertiary
S
N2 reactivity rates follow the trend CH
3X > primary > secondary > tertiary
The total reactivity is the sum of the two rates.
A graph showing the relative reactivities of the different alkyl halides towards S
N1 and S
N2 reactions. Also see Table 1.
| Table 1. Nucleophilic substitutions on RX (an alkyl halide or equivalent) |
| Factor | SN1 |
SN2 |
Comments |
| Kinetics |
Rate=k[RX] |
Rate=k[RX][Nuc] |
| Primary alkyl substrate |
Never unless
additional stabilising
groups present |
Good unless
a hindered nucleophile is used |
|
| Secondary alkyl substrate |
Moderate |
Moderate |
|
| Tertiary alkyl substrate |
Excellent |
Never |
Elimination likely
if heated or if
strong base used |
| Leaving group |
Important |
Important |
For halogens,
I > Br > Cl >> F |
| Nucleophilicity |
Unimportant |
Important |
|
| Preferred solvent |
Polar protic |
Polar aprotic |
|
| Stereochemistry |
Racemisation
(+ partial inversion
possible) |
Inversion |
|
| Rearrangements |
Common |
Rare |
Side reaction |
| Eliminations |
Common, especially
with basic nucleophiles |
Only with heat &
basic nucleophiles |
Side reaction
esp. if heated |
Nucleophilic substitution reactions
There are many reactions in organic chemistry that involve this type of mechanism. Common examples include
Besides S
N1 and S
N2, other mechanisms are known, although they're less common. The
SNi mechanism is observed in reactions of
thionyl chloride with
alcohols, and it's similar to S
N1 except that the nucleophile is delivered from the same side as the leaving group.
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 S
N1' or S
N2' reaction (depending on the kinetics). With
allylic halides or sulphonates, 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:
» CH
3CH=CH-CH
2-Cl → CH
3CH=CH-CH
2-OH + CH
3CH(OH)-CH=CH2
The
Sn1CB mechanism appears in
inorganic chemistry.
Nucleophilic substitution at unsaturated carbon centres
Nucleophilic substitution via the S
N1 or S
N2 mechanism doesn't generally occur with vinyl or aryl halides or related compounds. Under certain conditions nucleophilic substitutions may occur, via other mechanisms such as those described in the
nucleophilic aromatic substitution article.
When the substitution occurs at the
carbonyl group, the
acyl group may undergo
nucleophilic acyl substitution. This is the normal mode of substitution with
carboxylic acid derivatives such as
acyl chlorides,
esters and
amides.
Further Information
Get more info on 'Nucleophilic Substitution'.
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