Nucleophilic Substitution

X + Nu

nucleophilicsubstitution

Nu + X

Nucleophilic Substitution

Nu

X

is the nucleophile

is the leaving group

+ Nu

nucleophilicsubstitution

+CH3 Br CH3 Nu Br

Nucleophile ProductHO

CH3O

CH3OH

CH3OCH3

H3N CH3NH3

Base

CH3OH

H2O CH3 OH

H

Br OH-OH

Br

NH3

NH3

But where do alkyl bromides come from?

HBrBr

BrOH HBr

But what about a primary bromide?

Nucleophilic Substitutionworks both ways!

Mechanisms of Nucleophilic Substitution Reaction

There is more than one.

The mechanisms are determinedby studying the rate of the reaction.

A rate of a reaction refers to thechange in concentration of thereactants or products versus time.

First Case:

Rate =

BrCH3 NuCH3 Br +Nu+

- d [CH3Br] d t

= k [CH3Br] [Nu]

The rate that the CH3Br disappearsis proportional to the concentration ofthe CH3Br and the concentration of thenucleophile.

First Case:

Rate =

BrCH3 NuCH3 Br +Nu+

- d [CH3Br] d t

= k [CH3Br] [Nu]

The rate depends on the concentrationof two components so it is a bimolecularreaction.

First Case:

BrCH3 NuCH3 Br +Nu+

The reaction is called an:

SN2 reactionS for substitutionN for nucleophilic2 for bimolecular

H

+

+HO- CH3Br

HOCH3 Br-

TransitionState

Ea

HO Br

H

HH

HO Br

Transition State. Exists only for a very short time.

The key step in the reaction isa collision between the two reactants.

This means that an increase inthe concentration of either reactantwill result in a direct increase in therate.

Rate = - d [CH3Br] d t = k [CH3Br] [OH-]

Second Case: Kind of Strange

(CH3)3COH(CH3)3CBr

Br+OHHO

Br

No substitution with HO-, but reacts with H2O

Nosubstitution

H2O

OH + HBr

(CH3)3COH

No substitution with HO-, but reacts with H2O

HO- is much more basic than H2O.It should be a better nucleophile.

Most interestingly the rate does notdepend upon how much H2O is present.

Rate = - d [(CH3)3CBr] d t

= k [(CH3)3CBr]

The rate does not depend upon concentration of H2O

The key step in the reaction can notbe bimolecular. It must be unimolecular.

CH3

CH3 CH3

Br + Br

(CH3)3CBr (CH3)3C

It turns out to be a multi step reaction:Step one is ionization to give thet-butyl carbocation and bromide.

(CH3)3COH

OH

H+

(CH3)3COH2+

OH

HH2O

(CH3)3C

Br + Br

(CH3)3CBr (CH3)3CStep 1

Step 2 Step 3

The key is the relative rate of the steps.

Slow

Fast Fast

Br + Br

(CH3)3CBr (CH3)3CStep 1Slow

The slow step determines therate of the reaction. It is unimolecular.

Rate = - d [(CH3)3CBr] d t

= k [(CH3)3CBr]

The reaction is called an:

SN1 reactionS for substitutionN for nucleophilic1 for unimolecular

(CH3)3CBr

Br CH3 Br

Why does t-butylbromide react viaan SN1 reaction while methylbromidereacts via an SN2 reaction?

Size Matters

HO

Steric Hindrance

Why does t-butylbromide react viaan SN1 reaction while methylbromidereacts via an SN2 reaction?

1. Steric Hindrance

2. More stable carbocation

CH3

CH3CH3

H

HHversus

Ea

(CH3)3C Br(CH3)3C OH2+ H2O

+ Br-

Transition State

Br

Intermediate Transition State

OH

H

Transition States occur at amaximum of a Energy Profile.

Intermediates occur at a minimumof an Energy Profile. They arepotentially isolatable species.

T.S. T.S.

Int.