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.