Aliphatic Nucleophilic Substitution Reaction - SN2 Reaction

Aliphatic Nucleophilic Substitution Reaction

Contents

• Aliphatic substitution reaction

• Nucleophile

• Leaving group

• Bimolecular substitution reaction

• Mechanism

• Factors affecting rate of reaction

• Structure of the substrate

• Concentration and reactivity of the nucleophile

• Effect of the solvent

• Nature of the leaving group

• Stereochemistry of SN2 Mechanism

Learning Objectives

At the end of this lecture, student will be able to

• Explain substitution reaction

• Classify nucleophile & leaving group

• Explain kinetics and mechanism involved in SN2 reaction

• Explain factors affecting rate of SN2 reaction

• List out the factors affecting rate of SN2 reaction

• Explain the stereochemistry of SN2

Substitution Reaction

• Definition

Z +    R     X   à   R    Z +  X

• Aliphatic nucleophilic substitution reaction

• Components required

– Substrate

– Nucleophile

– Solvent

Nucleophile

• Definition

– Nucleus loving

– Electron rich

– Attacking reagents

• Types

– Negative nucleophile

– Neutral nucleophile

Examples

• Negative nucleophile: Cl‾, OH‾, CN‾, OR‾, H‾, X‾, SH‾

• Neutral nucleophile: NH3, H2O, ROH, RSH, ROR

Leaving Group

• Definition

• Good leaving group

– Weak base

– Halide ion

• Leaving ability among halogens

I‾ > Br‾ > Cl‾ >F‾

• Example

Mechanism of Aliphatic Nucleophilic Substitution

• SN1 – substitution nucleophilic unimolecular

• SN2 – substitution nucleophilic bimolecular

SN2 Reaction

• Definition

– Bimolecular nucleophilic substitution

• Example

• Kinetics

– 2nd order kinetics

– Rate α [substrate] [nucleophile]

– Rate = k [CH3Br] [OH‾]

• Mechanism

– Backside attack

Factors affecting the rates of SN2 reaction

• Structure of the substrate

• Concentration and reactivity of the nucleophile

• Effect of the solvent

• Nature of the leaving group

• Structure of the substrate

– Reactivity order

– Reason

• Steric hindrance

a. SN2 reaction of methyl bromide with hydroxide ion

b. SN2 reaction of sterically hindered alkyl halide with hydroxide ion

• Concentration & strength of nucleophile

– Strong & high concentration of nucleophile

• Solvents

– Polar aprotic solvents

• Leaving group

– Good leaving groups

– Weak bases

– Halide ions

Role of solvents

• Polar protic solvents

– Decreases the rate of SN2 reaction

– E_act is high

• Polar aprotic solvents

Increases the rate of SN2 reaction

– Solvate cations very well

– No hydrogen bonding

– Anions reactive as nucleophiles

• Polar aprotic solvents

Stereochemistry of SN2

• Walden inversion

• Nucleophile attacks carbonfrom side opposite bond to the leaving group

Inversion of Configuration

Stereospecific Reaction

• Stereoisomeric starting materials give stereoisomeric products

• The reaction of 2-bromooctane with NaOH (in ethanol-water) is stereospecific.

•   (+)-2-Bromooctane           (–)-2-Octanol

•   (–)-2-Bromooctane             (+)-2-Octanol

Summary

• Alkyl halides readily undergo nucleophilic substitution reactions

• Nucleophile is electron rich, nucleus loving reagents

• Nucleophile substitutes for halogen which is the good leaving group

• SN2 reaction is bimolecular - 2 molecules involved in the rate determining step

• Nucleophile attacks the back side of the carbon that is attached to the halogen

• Rate of SN2 reaction depends on steric hindrance

• Bulkier the groups at the backside of the carbon slower the reaction

• Methyl halides and primary alkyl halides readily undergo SN2 reaction

• Rate of SN2 reaction is favoured by strong & high concentration of nucleophile in polar aprotic solvents

• SN2 reaction involves complete inversion of configuration – Walden inversion

• Back side attack is preferred