Chapter 5:- Alkyl halides and Grignard Reagent 1st year Book
Organic Chemistry
(Page 3)

Stereochemistry of Nucleophilic Substitution Reactions and Mechanism | SN1 and SN2 Reaction

Hallmark reactions of alkyl halides are nucleophilic substitution reactions. Several distinct mechanisms ars possible for aliphatic nucleophilic substitution reactions. Depending upon the nature of substrate reactions are as follows :

[A] Mechanism and Stereochemistry of Bimolecular Nucleophilic Substitution (SN2) Reactions:

Hydrolysis of the primary halides viz. bromomethane in an aqueous base (NaOH) to form methanol is a typical example. SN1 and SN2 Reaction
Stereochemistry, SN2, methyl bromide to methyl alcohol formation
It is a one-step process with no intermediate. In this mechanism, there is a backside attack. The nucleophilic approaches the substrate from a position 180∘ away from the leaving group. SN1 and SN2 Reaction
Mechanism: Ingold has supported a transition state in which the attacking ion becomes partially bonded to the reacting carbon before the bromide ion has completely detached from it. 
Stereochemistry of Bimolecular Nucleophilic Substitution, SN2
The energy necessary to break the C−Br bond is supplied by the simultaneous formation of the C−OH bond. When the transition state is reached, the central carbon atom has gone from its initial sp3 hybridization to an sp2 hybridized state with an approximately perpendicular p – orbital. One lobe of the orbital overlaps with the nucleophile and the other with the leaving group as shown below –
Mechanism and Stereochemistry of Bimolecular Nucleophilic Substitution (SN2) Reactions central carbon atom
During the transition state, the three non-reacting groups and the central carbon atom are approximately coplanar. The potential energy profile of the reaction is shown in fig 5.03. It is evident that there is only one transition state and no intermediates between the reactants and products. The reaction is exothermic since the energy of the reactants is slightly higher than that of the products.

Evidence for the SN2 Mechanism :

  1. Kinetics:

Since both the substrate (CH3Br and OH−)are involved in the rate-determining step, the reaction would be first order with respect to each component and second order overall. The rate law can be expressed as :

 Rate = k[CH3Br][OH]
in general,
 Rate =k [ substrate ] [ nucleophile ] 
Since both molecules are taking part in the single rate-determining step, it is therefore would be a bimolecular reaction as well. The ‘ 2 ‘ of SN2 stands for bimolecular.
Evidence for the SN2 Mechanism, A plot of energy vs progress of SN2 reaction
The plot shows the concentration of substrate; [CH3Br ] as well as the nucleophile; [OH] are responsible for the rate. If a large excess of nucleophiles is present, e.g. if ‘ s ‘ is the solvent acting as the nucleophile, the mechanism may still be bimolecular. The experimentally determined kinetics will be first order.
 Rate =k [ substrate ] 
Such kinetics are called ‘pseudo first order.’ Therefore, it must be remembered that it is not always the second order:
  1. Stereochemistry:

Since the incoming nucleophile attacks the alkyl halide from the back side, the is an inversion of the configuration of the molecule which is called ‘Walden inversion‘. SN2 reactions are therefore referred as ‘stereospecific reactions‘ due to the above-said phenomena. If the reaction is carried out with an enantiomerically pure reactant (say R-configuration) an enantiomerically pure product with inversion of configuration is obtained. This is very strong evidence for the SN2 mechanism because it underlines the backside attack which eventually leads to an inversion of configuration.

R- Configuration,  S- Configuration, Stereochemistry

  1. Formation of a single Substitution Product:

Usually, SN2 reactions yield a single substitution product and it is evident that these are single-step reactions. We know that SN1 reactions are often accompanied by rearrangement as they involve carbocation intermediate.

4. No Substitution at Bridgehead Carbons :

It is found that the potential leaving group at bridgehead carbon atoms does not undergo an SN2 reaction. In these cases of the bridgehead, a carbon backside attack is not possible. We know that backside attack has been the basic criterion for the SN2 mechanism. For example, Bromo-3, 3- dimethyl bicyclo[2,2,2] octane does not form a substitution product with ethoxide ion, whereas the open chain analogous undergoes the reaction readily.
Stereochemistry- bromination-reaction

[B] Mechanism and Stereochemistry of Unimolecular Nucleophilic Substitution (SN1) Reactions.

The hydrolysis of tertiary butyl bromide and the formation of tertiary butyl alcohol is a typical example of an S: reaction. In contrast to methyl bromide hydrolysis; the rate of hydrolysis of tert. butyl bromide is not increased by the addition of sodium hydroxide even though hydroxide ions are consumed in the reaction.
Mechanism and Stereochemistry of Unimolecular Nucleophilic Substitution (SN1) Reactions
Kinetic theory revealed that the rate of reaction depends only on the concentration of tert. butyl bromide.
 Rate =k[(CH3)3Br]
Therefore, the mechanism is called SN1 which means substitution nucleophilic unimolecular.


The rate law suggests that the mechanism involves the following two stages :
Step I: It is slow to step in which the carbon-halogen bond undergoes heterolysis to form a carbocation intermediate. Indeed, this is the rate-determining step.
tert-butyl-bromide, tert-butyl-carbocation
Step II: This step is a fast combination of the intermediate carbocation with the nucleophile; OH−ion to yield the substitution product.
carbon atom fast reaction
This step is so fast that it does not affect the rate of the reaction. Since in the first step which is the rate-determining step the nucleophile plays no role, the addition of nucleophiles does not increase the rate of reaction. However, the nucleophile; OH−is used up in the second step. The potential energy profile( figure 5.04) clearly shows that the reaction occurs through a transition state with a carbocation intermediate.
Mechanism and Stereochemistry of Unimolecular Nucleophilic Substitution (SN1) Reactions-A plot of energy vs progress of SN1 reaction
The first step is energy consuming – endothermic and the corresponding transition state has a higher energy of activation (Ea). This high energy transition state makes the first step as the rate-determining of an SN1 reaction. The second step is exothermic as it involves the combination of a carbocation and a nucleophile to form the substitution product. Obviously, the transition state II (T.S.II) is of lower energy, and the second Ea is low. That is why the concentration or strength of the nucleophile does not affect the rate of an SN1 reaction.

 Evidences for SN1 Reaction :

  1. Kinetic:

The SN1 reaction is a first-order reaction and the rate law is given below as :

 Rate = k[(CH3)3C−Br]
 Rate = k[ substrate ] in general 
Thus, the rate of the SN1 reaction depends only on the concentration of substrate and it is independent of the other concentration and strength of the attacking nucleophile.
Figure 5.05 shows that
(i) the slope of graph I is the first-order rate constant, hence
 Rate =k1[(CH3)3C−Br]
(ii) the slope of graph II is equal to zero, hence the concentration of OH does not exceed the reaction rate. Thus, kinetics is very strong evidence for the SN1 mechanism.
  1. Stereochemistry:

We have seen that a carbocation intermediate is involved in the SN2 reaction. A carbocation is a planar species with the central positively charged sp2 hybridized carbon. All three substituents lie in a plane and 120 apart with the unhybridized empty p – orbital perpendicular to the plane. Now if the carbocation is generated from a chiral alkyl halide, the attack of nucleophiles can occur at either lobe of the empty p – orbital with equal possibility. Attack from the front side ( the side where the leaving group was previously attached) gives a product with retention of configuration. On the other hand, if the attack of nucleophiles occurs from the back side, a product with inversion of configuration (15−20%) is formed. Thus, the SN1 reaction of an optically active (chiral) alkyl halide will lead to a certain degree of racemization. However, due to the shielding of the leaving group backside attack is still preferred.

Stereochemistry of SN1 Reaction
Stereochemistry of SN1 Reaction
  1. Formation of Rearranged products:

Rearrangement is one of the characteristic features of carbocations as they tend to attain the most stable configuration. Therefore, the formation of rearranged products is an indication of the SN1 mechanism. For example ;

Stereochemistry of SN1 Reaction

There is a greater number of by-products in the case of the SN1 reaction as compared to SN2 ( which is a single step to reaction proceeding through an intermediate that does not undergo rearrangement) is classic evidence that succeeding through an intermediate.
  1. No Substitution at Bridgehead Carbon:

Substitution reaction following the SN1 mechanism either does ist take part or proceeds very slowly at bridgehead carbons, like SN2 mechanisms, though for different masons. Because of the rigid cage-like structure of the substrate, bridgehead carbons can not attain planarity. – Ance, heterolysis leading to the formation of a carbocation is also prevented. As a result bridgehead carbons are resistant to substitution by the SN1 mechanism.

No Substitution at Bridge head Carbon

Differences between SN1 and SN2 mechanism :

SN1 Mechanism SN2 Mechanism
1. This mechanism involves first-order kinetics. 1. This mechanism involves second-order kinetic
2. This is a two-step mechanism 2. This is one step mechanism.
3. Rate depends mainly on electronic factors. 3. Steric and non-electronic factors influence the rate of reaction
4. Partial racemization occurs, where possible. 4. Complete stereochemical inversion occurs, where possible.
5. Frequent rearrangement takes place. 5. No rearrangement occurs.
6. Reactivity sequence depends on the structure of halides e.g. 6. The reactivity sequence is methyl halide > 1º > 2º > 3º.
7. Tertiary alkyl halides are the common substrate. 7. Primary alkyl halides are the common substrate.
8. Mid nucleophiles like alcohols, water, etc. favor it. 8. Reaction is favored by nonpolar solvents
9. Reaction is favored by polar solvent 9. Reaction is favored by nonpolar solvents
10. Nucleophilic substitution by SN1 mechanism takes place as follows:

Nucleophilic substitution by SN1 mechanism takes place as follows

10. Nucleophilic substitution by SN2 mechanism takes place as follows:


Nucleophilic substitution by SN2 mechanism takes place as follows

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