Substitution Reactions – SN1
Recall that the following reaction does not proceed via an SN2 mechanism. The
electrophilic carbon atom is too sterically crowded for the nucleophile to attack
it. For this type of substrate, the reaction proceeds by a different mechanism,
an SN1 mechanism.
I
+ (H3C)3C
Br
I
C(CH3)3
+
Br
SN1 mechanisms always proceed via a carbocation intermediate in the rate
determining step. The nucleophile then quickly attacks the carbocation to form the
products:
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Substitution Reactions – SN1
There may be more steps depending on the electrophile and/or nucleophile.
H2O
+
(H3C)3C
Br
(H3C)3C
OH +
H
+ Br
Reactions in which the solvent participates as the nucleophile are known as solvolysis
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reactions.
Substitution Reactions – SN1
Sketch a reaction profile diagram for the following reaction:
I
+ (H3C)3C
Br
I
C(CH3)3
+
Br
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Substitution Reactions – SN1
SN1 reactions predominate when:
•A relatively stable carbocation is formed.
•The solvent is polar and protic.
•The nucleophile is a weak base (preferably a neutral molecule like H2O,
ROH, etc.).
Carbocation Stability
Carbocation stability is dependent on:
•Delocalization (resonance).
•Hyperconjugation.
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Carbocation Stability – Resonance Delocalization
We have already seen how a delocalized charge is more stable than a localized one.
For each of the following molecules, form the carbocation and draw all reasonable
resonance structures:
CH2 Cl
H
H2C
C
Br
C
H
H
H3C
H2
C
O
Cl
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Carbocation Stability – Resonance Delocalization
Note that aryl and vinyl carbocations cannot be stabilized by resonance.
The empty p-orbital is orthogonal to the π-system and as such cannot be
delocalized:
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Carbocation Stability – Inductive effects and Hyperconjugation
Carbocations can also be stabilized by inductive effects. That is, electron rich
groups can donate electron density through the sigma bonds to help stabilize a
carbocation:
Inductive effects are enhanced by hyperconjugation, a phenomenon where
electron rich sigma MOs overlap with the empty p-orbital of the carbocation.
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Carbocation Stability
Just as aryl and vinyl carbocations are not stabilized by resonance, they are also not
stabilized by hyperconjugation:
Considering these effects, we can arrange the different types of carbocations on the :
3 w/ resonance
>
3 w/out resonance
or
2 w/ resonance
>
2 w/out resonance
or
1 w/ resonance
>>
1 w/out resonance
> methyl >
vinyl
or
aryl
The type of carbon atoms highlighted in
red do not form carbocations in most cases
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SN1 - Rearrangements
One consequence of reactions proceeding via carbocation intermediates is the
occurrence of rearrangement side reactions. Consider the following reaction:
The substitution product is a constitutional isomer of the product expected. Propose a
mechanism for the above reaction:
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SN1 - Rearrangements
It is worth noting that carbocation
rearrangements can involve
shifting either a hydride ion or a
methyl anion. In either case, you
will always be forming a more
stable carbocation.
Pay close attention to the way
curly arrows are drawn when
proposing a hydride or methyl
shift. We should be able to tell if
you’re proposing a hydride shift or
generation of a pi bond.
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The SN1 Reaction - Kinetics.
I - + (CH3)3CBr → (CH3)3CI + Br Consider:
•What happens to the rate of production of (CH3)3CI if the concentration of I- is
held constant and the concentration of (CH3)3CBr is increased?
•What happens to the rate of production of (CH3)3CI if the concentration of
(CH3)3CBr is held constant and the concentration of I- is increased?
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The SN1 Reaction - Kinetics.
I - + (CH3)3CBr → (CH3)3CI + Br -
As we did for the SN2 reaction, we can also write a rate law for the SN1 reaction:
Considering what happens to the concentrations of reactants, what would a graph
or reaction rate vs. time look?
Again, as with the SN2 reaction, this type of graph is not that useful since we
cannot predict the rate of reaction at some future time. In order to do so we would
need to convert the graph into a linear function which is outside the scope of this
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course.
The Stereochemistry of the SN1 reaction
Unlike in an SN2 reaction, an SN1 reaction at an asymmetric carbon generates a
racemic mixture of products.
Br
NaI/Acetone
C
H3C
H3C
CH2CH3
Ph
C
CH2CH3
Ph
I
C
H3C
H3C
CH2CH3
Ph
C
CH2CH3
Ph
I
The nature of the intermediate is such that the nucleophile can attack from either side
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with equal likelihood.
The Stereochemistry of the SN1 reaction
Sometimes (depending on conditions) reactions occur with only partial
racemization.
Br Br
NaI/Acetone
C
H3C
H3C
CH2CH3
Ph
C
CH2CH3
Ph
I
C
H3C
CH2CH3
Ph
H3C
C
CH2CH3
Ph
I
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SN1 and SN2 reactions – Solvent Effects
SN1 reactions are typically done in polar protic solvents. Polar protic solvents are
used because they help stabilize the transition state during the process of forming
the carbocation intermediate. The more stabilized the transition state, the faster the
carbocation will form:
Some common polar protic solvents:
O
OH
C
H3C
OH
Acetic Acid t-Butanol
AcOH
(t-BuOH)
OH
Isopropanol
(iPrOH)
CH3CH2OH
Ethanol
(EtOH)
CH3OH
H2O
Methanol
(MeOH)
Water
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SN1 and SN2 reactions – Solvent Effects
SN2 reactions are typically done in polar aprotic solvents. These solvents are
polar enough to solubilize the nucleophile but don’t stabilize the nucleophiles
enough to prevent reaction:
Some common polar aprotic solvents:
O
O
H3C
C
H3C
CH3
Acetone
C
N
CH3OCH2CH2OCH3
Acetonitrile
(MeCN)
Dimethoxyethane
(DME)
C
H
N(CH3)2
Dimethylformamide
(DMF)
O
H3C
O
O
S
CH3
Dimethyl sulfoxide
(DMSO)
H3CH2C
CH2CH3
Ethyl ether
(Et2O)
N
Pyridine
(Pyr)
Tetrahydrof uran
(THF)
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SN1 vs. SN2 reactions – Comparison
SN2
SN1
Reaction Order
second order reaction
first order reaction
Minimum # Steps
1 or more steps
2 or more steps
Intermediates?
not necessarily
carbocation
Stereochemical
Consequences
stereospecific inversion of
configuration at electrophilic site
racemization (full or partial)
at electrophilic site
Importance of
Nucleophile Strength
very important; no reaction unimportant
for weak nucleophiles like H2O
Importance of
Leaving Group
very important; no reaction for
weak leaving groups like HO-
very important; no reaction for
weak leaving groups like HO-
Substrate Structure
Dependence
avoid steric hindrance;
CH3 > 1 > 2(slow) > 3 (no);
no reaction for aryl/vinyl
need carbocation stabilization;
3 > 2 (slow) > 1 (no);
resonance stabilization helps;
no reaction for aryl/vinyl
Solvent
polar aprotic
polar protic
Competing Reactions
E2
E1, E2, rearrangement
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SN1 vs. SN2 reactions
Would you expect the following reactions to proceed via SN1, SN2, both, or neither ?
Draw the expected product(s) for each reaction.
NaI
acetone
Ag+
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