Aliphatic Nucleophilic substitution

Aliphatic Nucleophilic substitution reactions

1. Aliphatic Nucleophilic Substitution Prof. A.Ramachandran Assistant Professor in Chemistry GCE, Salem-11

2. Definition Nucleophilic substitution reaction involves the displacement of a nucleophile by another nucleophile The nucleophile furnishes an electron pair to the carbon from which the leaving group departs with the bonding pair of electrons.

3. Types of Nucleophilic Substitution reactions Unimolecular Nucleophilic Substitution reaction (S N 1 ) Bimolecular Nucleophilic Substitution reaction (S N 2 ) Internal Nucleophilic Substitution reaction ( S N i )

4. S N 1 MECHANISM The S N 1 reaction is a nucleophilic substitution reaction where the rate determining step is unimolecular . The rate of the reaction is dependent on one of the reactants, the reaction is a first order reaction. Rate [R 3 C-X ] The product is formed through formation of carbocation intermediate. Hence it follows two step mechanism.  

5. S N 1 MECHANISM Taking the hydrolysis of tertiary butyl bromide as an example, Step 1 The carbon-bromine bond is a polar covalent bond. The cleavage of this bond allows the removal of the leaving group (bromide ion). When the bromide ion leaves the tertiary butyl bromide, a carbocation intermediate is formed. It is important to note that the breaking of the carbon-bromine bond is endothermic . The first step is reversible and slow one. Hence it shows rate determining step.

6. S N 1 MECHANISM Step I: Overall Carbocation Rate determining step Reversible

7. S N 1 MECHANISM Step II: In the second step of the SN1 reaction mechanism, the carbocation is attacked by the nucleophile . A rapid attack of OH – on the carbocation completes the hydrolysis . A carbocation is flat (SP 2 , trigonal planar) with the vacant 2P orbital vertical to the plane bearing the three groups, the attack of the reagent can occur from either side of the plane with equal probability, i.e. a racemic product should result if the alkyl halide is chiral.

8. S N 1 MECHANISM Step II: Retention Inversion Racemization

9. S N 1 MECHANISM Effect of Solvent A solvent that can facilitate the formation of the carbocation intermediate will speed up the rate determining step of the S N 1 reaction. The preferred solvents for this type of reaction are both polar and protic . The polar nature of the solvent helps to stabilize ionic intermediates whereas the protic nature of the solvent helps solvate the leaving group. Examples of solvents used in S N 1 reactions include water and alcohols. These solvents also act as nucleophiles.

10. S N 1 MECHANISM Effect of Substrate A tertiary carbocation being stabilized by three electron releasing groups. Allylic and benzylic halides can also react by an S N 1 mechanism since these substrates can form relatively stable carbocation. T he order of hydrolysis of alkyl halides by S N 1 path is: Benzyl, Allyl> tert - > Sec-> primary > CH 3

11. S N 2 MECHANISM Nucleophilic substitution reactions which follow second-order kinetics are called S N 2 T he rate of hydrolysis of methyl bromide with NaOH has been found to be of second order, i.e., R ate [CH 3 Br] [OH - ] T he reaction is a concerted one step reaction without any intermediate.  

12. S N 2 MECHANISM A collision between the two reactants resulting in the direct displacement of Br - by OH - occurs. While a new C-OH bond is being formed, the C-Br bond starts breaking, i.e. the bond formation and the bond breaking are simultaneous. During the collision an energetic hydroxide ion approaches the methyl bromide molecule from the side opposite to bromine to avoid repulsion, i.e. at 180° to the leaving group- a back- side attack.

13. S N 2 MECHANISM A state is reached when the OH and Br are partially bonded to the central carbon and the non- participating groups lying in a plane perpendicular to the line HO….C….Br. This state is called the transition state. In the transition state partial negative charge of the hydroxide ion is transferred to bromine via the carbon atom. With further approach of hydroxide, a complete C-OH bond is formed and bromine departs with the bonding pair of electrons.

14. S N 2 MECHANISM Inversion Transition state Overall

15. S N 2 MECHANISM Effect of Substrate : The optimum substrate would be CH 3 -X. Each replacement of hydrogen by a more bulky alkyl group should decrease the rate of reaction. Consequently, the order of reactivity of alkyl groups is expected to be M ethyl > primary > secondary > tertiary

16. S N i MECHANISM S N i means Substitution Nucleophilic Internal mechanism It follows second-order kinetics with no change in the configuration of the product. Best example is the esterification of chiral alcohols with thionyl chloride, which results in the retention of configuration of the product The rate of the reaction is found to be dependent on both the reactants, R ate [ PhCH (Me)OH] [ SOCl 2 ]  

17. S N i MECHANISM Overall

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