6 Nucleophilic Substitution Reactions

Reaction with Sodium Hydroxide

The reactions proceed in 2 different reaction mechanisms: bimolecular nucleophilic substitution (S_N2)

unimolecular nucleophilic substitution (S_N1)

Bimolecular Nucleophilic Substitution (S_N2)

Example: CH₃ – Cl + OH^– ®¾ CH₃OH + Cl^–

Rate = k[CH₃Cl][OH^–]

Order of reaction = 2 Þ both species are involved in rate determining step

Reaction mechanism of the S_N2 reaction:

• The nucleophile attacks from the backside of the electropositive carbon centre

• In the transition state, the bond between C and O is partially formed, while the bond between C and Cl is partially broken

Transition state involve both the nucleophile and substrate Þ second order kinetics of the reaction

Stereochemistry of S_N2 Reactions

• The nucleophile attacks from the backside of the electropositive carbon centre

• The configuration of the carbon atom under attack inverts

Unimolecular Nucleophilic Substitution (S_N1)

Example:

Kinetic study shows that: Rate = k[(CH₃)₃CCl]

• The rate is independent of [OH–]

• Order of reaction = 1 Þ only 1 species is involved in the rate determining step

Reaction mechanism of S_N1 reaction involves 2 steps and 1 intermediate formed

Step 1:

• Slowest step (i.e. rate determining step)

• Formation of carbocation and halide ion

Step 2:

• Fast step

• Attacked by a nucleophile to form the product

• Rate determining step involves the breaking of the C – Cl bond to form carbocation

• Only 1 molecule is involved in the rate determining step Þ first order kinetics of the reaction

Stereochemistry of S_N1 Reactions

• The carbocation formed has a trigonal planar structure

• The nucleophile may either attack from the frontside or the backside

For some cations, different products may be formed by either mode of attack

The reaction is called racemization

The above S_N1 reaction leads to racemization. Formation of trigonal planar carbocation intermediate

The attack of the nucleophile from either side of the planar carbocation occurs at equal rates and results in the formation of the enantiomers of butan-2-ol in equal amounts

Factors Affecting the Rates of S_N1 and S_N2 Reactions:

Most important factors affecting the relative rates of S_N1 and S_N2 reactions:

1. The structure of the substrate

2. The concentration and strength of the nucleophile (for S_N2 reactions only)

3. The nature of the leaving group

The Structure of the Substrate

1. Sn2 reactions

• The reactivity of haloalkanes in S_N2 reactions: CH₃X > 1° haloalkane > 2° haloalkane > 3° haloalkane

• Steric hindrance affects the reactivity bulky alkyl groups will inhibit the approach of nucleophile to the electropositive carbon centre Þ energy of transition state­ Þ activation energy ­

Steric effects in the S_N2 reaction

2. Sn1 reactions

• Critical factor: the relative stability of the carbocation formed

• Tertiary carbocations are the most stable 3 electron-releasing alkyl groups stabilize the carbocation by releasing electrons

• Methyl, 1°, 2° carbocation have much higher energy Þ activation energies for S_N1 reactions are very large and rate of reaction become very small

The Concentration and Strength of the Nucleophile

• Only affect S_N2 reactions

• Concentration of nucleophile ­ Þ rate ­

Relative strength of nucleophiles can be correlated with two structural features:

(I) A negatively charged nucleophile (e.g. OH–) is always a stronger nucleophile than a neutral nucleophile (e.g. H₂O)

(II) In a group of nucleophiles in which the nucleophilic atom is the same, the order of nucleophilicity roughly follows the order of basicity:

e.g. RO– > OH– >> ROH > H₂O

Strength ­ Þ rate ­

The Nature of Leaving Group

• Halide ion departs as a leaving group

• For the halide ion, the ease of leaving: I– > Br– > Cl– > F–

• This is in agreement with the order of bond enthalpies of carbon-halogen bonds

• Uncharged or neutral compounds are better leaving groups e.g. The ease of leaving of oxygen compounds:

H₂O >> OH– > RO–

• Strongly basic ions rarely act as leaving group e.g.

When an alcohol is dissolved in a strong acid, it can react with a halide ion. The acid protonates the –OH group, and the leaving group becomes a neutral water molecule

Comparision of Rates of Hydrolysis of Haloalkanes and Halobenzene