Nucleophilic Substitution
Reactions:
SN1 Mechanism
Two Step Mechanism
Which step is rate determining?
A) Step #1
B) Step #2
Solvolysis Reactions
Tertiary alkyl halides are very unreactive in
substitutions that proceed by the SN2 mechanism.
But they are highly reactive in solvolysis
reactions where the solvent is generally one of
the reactants.
Hydrolysis of tert-butyl bromide.
CH3
CH3
C
H
..
Br :
..
+
CH3
: O:
H
+
O:
C
H
CH3
CH3
H
CH3
+
CH3
CH3
C
CH3
..
OH
..
+
H
..
Br :
..
.. –
: Br :
..
Hydrolysis of tert-butyl bromide.
CH3
CH3
C
CH3
H
..
Br :
..
+
: O:
CH3
CH3
H
+
O:
C
H
H
CH3
+
This is the nucleophilic substitution
stage of the reaction; the one with
which we are concerned.
.. –
: Br :
..
Hydrolysis of tert-butyl bromide.
CH3
CH3
C
CH3
H
..
Br :
..
+
CH3
: O:
CH3
H
+
O:
C
H
H
CH3
+
The reaction rate is independent
of the concentration of the nucleophile
and follows a first-order rate law.
rate = k[(CH3)3CBr]
.. –
: Br :
..
Hydrolysis of tert-butyl bromide.
CH3
CH3
C
CH3
H
..
Br :
..
+
CH3
: O:
CH3
H
+
O:
C
H
H
CH3
+
The mechanism of this step is
not SN2. It is called SN1 and
begins with ionization of (CH3)3CBr.
.. –
: Br :
..
Kinetics and Mechanism
rate = k[alkyl halide]
First-order kinetics implies a unimolecular
rate-determining step.
Proposed mechanism is called SN1, which
stands for
substitution nucleophilic unimolecular
CH3
CH3
Mechanism
..
Br :
..
C
CH3
unimolecular
slow
H3C
+
C
CH3
CH3
+
.. –
: Br :
..
Mechanism
H3C
CH3
+
C
H
: O:
CH3
H
bimolecular
fast
CH3
CH3
H
+
C
CH3
O:
H
carbocation
formation
R+
carbocation
capture
proton
transfer
RX
+
ROH2
ROH
Characteristics of the SN1 mechanism
first order kinetics: rate = k[RX]
unimolecular rate-determining step
carbocation intermediate
rate follows carbocation stability
rearrangements sometimes observed
reaction is not stereospecific
racemization occurs in reactions of
optically active alkyl halides
Question
What is the rate-determining step in the reaction
of cyclobutanol with HCl?
A) protonation of the OH group
B) attack of the bromide on the carbocation
C) simultaneous formation of the C-Br bond
and the breaking of the C-OH bond
D) carbocation formation
Question
The species shown below represents _____ of
the reaction between isopropyl alcohol and
hydrogen bromide.
A) the alkyloxonium ion intermediate
B) the transition step of the bimolecular
proton transfer
C) the transition state of the attack of the
nucleophile on the carbocation
D) the transition state of the unimolecular
dissociation
Carbocation Stability and SN1
Reaction Rates
Electronic Effects Govern SN1 Rates
The rate of nucleophilic substitution
by the SN1 mechanism is governed
by electronic effects.
Carbocation formation is rate-determining.
The more stable the carbocation, the faster
its rate of formation, and the greater the
rate of unimolecular nucleophilic substitution.
Reactivity toward substitution by the SN1
mechanism
RBr solvolysis in aqueous formic acid
Alkyl bromide
Class
Relative rate
CH3Br
Methyl
1
CH3CH2Br
Primary
2
(CH3)2CHBr
Secondary
(CH3)3CBr
Tertiary
43
100,000,000
Decreasing SN1 Reactivity
(CH3)3CBr
(CH3)2CHBr
CH3CH2Br
CH3Br
Question
Select the most stable carbocation.
A)
B)
C)
D)
Question
Which one of the following reacts with HBr at
the fastest rate?
A)
C)
B)
D)
Stereochemistry of SN1 Reactions
Generalization
Nucleophilic substitutions that exhibit
first-order kinetic behavior are
not stereospecific.
Stereochemistry of an SN1 Reaction
CH3
H
C
R-(–)-2-Bromooctane
Br
CH3(CH2)5
H
HO
CH3
C
(CH2)5CH3
(S)-(+)-2-Octanol (83%)
CH3
H2O
H
C
OH
CH3(CH2)5
(R)-(–)-2-Octanol (17%)
Figure
Ionization step
gives carbocation; three
bonds to chirality
center become coplanar
+
Leaving group shields
one face of carbocation;
nucleophile attacks
faster at opposite face.
Structure of tert-Butyl Cation
CH3
+
H3C
C
CH3
Positively charged carbon is sp2 hybridized.
All four carbons lie in same plane.
Unhybridized p orbital is perpendicular to
plane of four carbons.
+
More than 50%
Less than 50%
Carbocation Capture
+
H3C CH3
C+
Cl
–
CH3
Lewis acid
Lewis base
Electrophile
Nucleophile
H3C CH3
C
H3C
Cl
Carbocation Rearrangements
in SN1 Reactions
Because...
carbocations are intermediates
in SN1 reactions, rearrangements
are possible.
Example
CH3
CH3
CH3
H2O
C
CHCH3
H
Br
CH3
C
CH2CH3
OH
(93%)
H2O
CH3
CH3
C
H
CH3
CHCH3
+
CH3
C
+
CHCH3
H
Effect of Solvent
on the
Rate of Nucleophilic Substitution
In general...
SN1 Reaction Rates Increase
in Polar Solvents
SN1 Reactivity versus Solvent Polarity
Solvent
Dielectric
Relative
constant rate
acetic acid
methanol
formic acid
water
Most polar
Fastest rate
transition
state
stabilized by
polar solvent
 R
X 
R+
energy of RX
not much
affected by
polarity of
solvent
RX
transition
state
stabilized by
polar solvent
 R
X 
R+
energy of RX
not much
affected by
polarity of
solvent
RX
activation energy
decreases;
rate increases
In general...
SN2 Reaction Rates Increase in
Polar Aprotic Solvents
An aprotic solvent is one that does
not have an —OH group.
SN2 Reactivity versus Type of
Solvent
CH3CH2CH2CH2Br + N3–
Solvent
Type
Relative Rate
CH3OH
polar protic
1
H2O
polar protic
7
DMSO
polar aprotic
1300
DMF
Acetonitrile
p
polar aprotic
5000
Mechanism Summary
SN1 and SN2
When...
primary alkyl halides undergo nucleophilic
substitution, they always react by the SN2
mechanism
tertiary alkyl halides undergo nucleophilic
substitution, they always react by the SN1
mechanism
secondary alkyl halides undergo nucleophilic
substitution, they react by the
SN1 mechanism in the presence of a weak
nucleophile (solvolysis)
SN2 mechanism in the presence of a good
nucleophile
SN1 vs. SN2 – The Leaving Group
The most commonly used leaving groups are halides
and sulfonate ions.
CONCEPTUAL CHECKPOINT 7.28.
SN2 vs. SN1 – Solvent
SN2 reaction, use a polar, aprotic solvent
To promote an SN1 reaction, use a polar, protic
solvent: The protic solvent will hydrogen bond with
the nucleophile, stabilizing it, while the leaving group
leaves first.
Various Functions from Substitution Reactions
Calibrated Peer Review / Lab Experimentation
http://chemconnections.org/organic/chem226/calendar-f-12