Transcript Ch10-Sn1 - ChemConnections

Unimolecular Nucleophilic Substitution
SN1
A question...
Tertiary alkyl halides are very unreactive in
substitutions that proceed by the SN2 mechanism.
Do they undergo nucleophilic substitution at all?
Yes. But by a mechanism different from SN2.
The most common examples are seen in
solvolysis reactions.
The Sn1 Reaction
Example of a solvolysis. Hydrolysis of
tert-butyl bromide.
CH3
H
CH3
..
+ : O:
C Br :
..
H
CH
3
CH3
CH3
C
CH3
..
OH
..
+
H
..
Br :
..
Kinetics and Mechanism
rate = k [alkyl halide]
First-order kinetics implies a unimolecular
rate-determining step.
Mechanism is called SN1, which stands for
substitution nucleophilic unimolecular (1)
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 are observed
• Reaction is not stereospecific:
racemization in reactions of
optically active alkyl halides
Reaction Coordinate Diagram for an
SN1 Reaction
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
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%)
The carbocation reaction intermediate leads to the
formation of two stereoisomeric products
Step 1
Ionization step
gives carbocation; three
bonds to stereogenic
center become coplanar
+
Step 2
+
Leaving group shields
one face of carbocation;
nucleophile attacks
faster at opposite face.
+
More than 50%
Less than 50%
Carbocation Rearrangements
in SN1 Reactions
Because...
carbocations are intermediates
in SN1 reactions, rearrangements
are possible.
Carbocations
Carbocations rearrange to
the more stable form(s)
Carbocation Rearrangement
Mechanism
What is the starting carbocation: 1o, 2o or 3o?
What is the rearranged carbocation: 1o, 2o or 3o?
Carbocation Rearrangement
Example
CH3
CH3
CH3
H2O
C
CHCH3
H
Br
CH3
C
OH
CH2CH3
(93%)
Example
CH3
CH3
CH3
C
CHCH3
H
Br
CH3
C
CH2CH3
OH
(93%)
H2O
CH3
CH3
C
H
CH3
CHCH3
+
CH3
C
+
CHCH3
H
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
Putting things together