|Organic Chemistry 4e Carey|
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Nucleophilic Substitution reactions
Chapter 4: Alcohols and Alkyl Halides
Nucleophilic substitution will be explored in much more detail in chapter 8.
What does the term "nucleophilic substitution" imply ?
A nucleophile is
an the electron rich species that will react with an electron poor species.
A substitution implies that one group replaces another
SN1 indicates a substitution, nucleophilic, unimolecular reaction, described by the expression rate = k [R-LG]
This pathway is a multi-step process with the following characteristics:
|Multi-step reactions have intermediates and several transition states
In an SN1 there is loss of the leaving group generating an intermediate carbocation which then undergoes a rapid reaction with the nucleophile.
The reaction profiles shown here are simplified and do not include the equilibria for protonation of the -OH.
The following issues are relevant to the SN1 reactions of alcohols:
Effect of R-
Reactivity order : (CH3)3C- > (CH3)2CH- > CH3CH2- > CH3-
In an SN1 reaction, the key step is the loss of the leaving group to form the intermediate carbocation. The more stable the carbocation is, the easier it is to form, and the faster the SN1 reaction will be. Some students fall into the trap of thinking that the system with the less stable carbocation will react fastest, but they are forgetting that it is the generation of the carbocation that is rate determining.
More about carbocations
The only event in the rate determining step of the SN1 is breaking the C-LG bond. For alcohols it is important to remember that -OH is a very poor leaving. In the reactions with HX, the -OH is protonated first to give an oxonium, providing the much better leaving group, a water molecule (see scheme below).
Since the nucleophile is not involved in the rate determining step of an SN1 reaction, the nature of the nucleophile is unimportant. In the reactions of alcohols with HX, the reactivity trend of HI > HBr > HCl > HF is not due to the nucleophilicity of the halide ion but the acidity of HX which is involved in generating the leaving group prior to the rate determining step.
|In an SN1, the nucleophile attacks the planar carbocation. Since there
is an equally probability of attack on either face there will be a loss
of stereochemistry at the reactive center and both possible products
will be observed.
Since a carbocation intermediate
is formed, there is the possibility of rearrangements (e.g. 1,2-hydride
or 1,2-alkyl shifts) to generate a more stable carbocation (see later).
This is usually indicated by a change in the position of the halide compared
to that of the original -OH group, or a change in the carbon skeleton of the
product when compared to the starting material.
The general stability order of simple alkyl carbocations is: (most stable) 3o > 2o > 1o > methyl (least stable)
||Alkyl carbocations are sp2 hybridized, planar systems at the
cationic C center.
The p-orbital that is not utilized in the hybrids is empty and is often shown bearing the positive charge since it represents the orbital available to accept electrons.
|As they have an incomplete octet, carbocations are excellent electrophiles
and react readily with nucleophiles. Alternatively, loss of H+ can
generate a p bond.
The electrostatic potential diagrams clearly show the cationic center
in blue, this
is where the nucleophile will attack.
Carbocations are prone to rearrangement via 1,2-hyride or 1,2-alkyl shifts if it generates a more stable carbocation
1. Substitutions via the SN1
2. Eliminations via the E1
3. Additions to alkenes and alkynes (HX, H3O+)
SN2 indicates a substitution, nucleophilic, bimolecular reaction, described by the expression rate = k [Nu][R-LG]
This pathway is a concerted
process (single step) as shown by the following reaction coordinate diagrams,
where there is simultaneous attack of the nucleophile and displacement of the
|Single step reactions have no intermediates and single transition state
In an SN2 there is simultaneous formation of the carbon-nucleophile bond and breaking of the carbon-leaving group bond, hence the reaction proceeds via a TS in which the central C is partially bonded to five groups.
The reaction profiles shown here are simplified and do not include
the equilibria for protonation of the -OH.
The following issues are relevant to the SN2 reactions of alcohols:
Effects of R-
Reactivity order : CH3- > CH3CH2- > (CH3)2CH- > (CH3)3C-
For alcohols reacting with HX, methyl and 1o systems are more likely to react via an SN2 reaction since the carbocations are too high energy for the SN1 pathway to occur.
Once again the leaving group is a water molecule formed by protonation of the -OH group. -OH on its own is a poor leaving group.
Since the nucleophile is involved in the rate determining step, the nature of the nucleophile is very important in an SN2 reaction. More reactive nucleophiles will favor an SN2 reaction.
When the nucleophile attacks in an SN2 reaction, it is on the opposite side to the position of the leaving group. As a result, the reaction will proceed with an inversion of configuration.
Simultaneous formation of C-Br bond and cleavage of the C-O bond allows the loss of the good leaving group, a neutral water molecule, to give a the alkyl bromide. This is the rate determining step.