Download SN1 vs. SN2 Reactions - Master Organic Chemistry

SN1 Reaction
SN2 Reaction
Stereochemistry
Substitution occurs with a mixture of retention and inversion at a
stereocenter
Br
3
1
2
HO
H 2O
3
1
2
retention
2
1
4
2
3
4
2
3
Rate = k [R–Br]
+ H 3O Br
1
1
2
3
[
1
4
Br
]
[
2
3
(doubling the
concentration of
water has no
effect on the rate)
4
H 2O ]
Fastest for tertiary, slowest for primary
Tertiary
2
3
50°C
1
Br
Secondary
2
3
1
3
1
50°C
1
3
4
–H
Step 3:
deprotonation
H
HO
2
1
3
4
Path A
OH 2
1
H
Stepwise - leaving group
leaves (slow) forming a
carbocation, which is then
attacked by a nucleophile
(fast)
H 2O 2
(R)
1.2 × 10 6
11.6
+ H 3O Br
1
1
+ H 3O Br
2
(likely occuring through SN 2 mechanism)
From "March's Advanced Organic Chemistry", 5th Ed. p. 431
Mechanism
H
1
OH
H 2O
2
2
Rate
+ H 3O Br
OH
50°C
1
2
3
H 2O
Br
Primary
HO
H 2O
H
2
Br
3
1
Bonds
Broken
C2 –Br
C2 –CN
One stereoisomer
The rate of the reaction is sensitive to the concentration of the
substrate AND the nucleophile
Br
4
2
3
CN
C N
Na
4
1
3
2
Rate = k [R–Br] [
+ NaBr
1
1
OH 2
Path B
3
OH 2
2
4
(S)
–H
Step 3:
deprotonation
1
3
4
H
2
OH
(S)
Path B gives retention (S)
"Big Barrier"
1
2
[
3
4
Br
1
2
3
(doubling the
concentration of
CN doubles the rate)
4
[ :CN ]
]
Unimolecular
Bimolecular
(substrate only) (substrate and nucleophile)
Carbocation
stability
3° > 2° >>1°
(fastest)
Steric hindrance
1° > 2° >>3°
(fastest)
Weak (generally
neutral)
Strong (generally
bearing a negative
charge)
Solvent
Polar protic
(e.g. alcohols)
Polar aprotic
(e.g. DMSO, acetone)
Stereochemistry
Mix of retention
and inversion
Inversion
Comparing SN1 vs. SN2 reactions
Slowest for tertiary, fastest for primary (methyl even faster)
Br
Tertiary
4
Na
2
3
4
4
3
2
3
Methyl
2
1
H 3C
NC
C N
4
1
Br
Secondary
Primary
SN2
Nucleophile
Rate
Na
4
1
Br
Br
Na
Na
3
2
1
C N
4
2
3
2
3
C N
Rate
< 0.001
CN
C N
1
1
1
H
3
2
4
(S)
Br
The key skill to start with is identifying the leaving group
Look for halogens (Cl, Br, I) or tosylates/mesylates (OTs, OMs)
Alternatively, look for alcohols (OH) if acid is present
Once you've identified the leaving group, instpect the carbon it is
attached to. How many carbons is that carbon connected to? That
will tell you if the carbon is primary, secondary, or tertiary. If there are
no attached carbons, that's the special case of "methyl" (SN 2 for sure!)
CN
~20
If the carbon is tertiary, it's likely SN1. You can rule out SN 2 due to steric
hindrance.
If the carbon is primary, it's likely SN 2. You can rule out SN1 due to the fact that
primary carbocations are unstable [one exception: resonance stabilized
carbocations].
CN
~1000
Next, examine the nucleophile. A negatively charged nucleophile
generally indicates an SN 2 reaction. A neutral nucleophile (such as
H 2O or ROH) generally indicates an SN1 reaction.
1
H 3C
1
N C
H
Rate Law
CN]
Finally, check the solvent. A polar aprotic solvent (such as DMSO,
acetone, acetonitrile, or DMF) generally indicates SN 2, whereas a
polar protic solvent such as H 2O or ROH generally indicates SN1
conditions.
In the "backside attack", the nucleophile attacks the substrate from the backside
in a single step, resulting in inversion of configuration.
Br
SN1
Alkyl halide
(electrophile)
Rate Law
One step (backside attack)
(S) alkyl halide
Carbocation
4
(R)
Path A gives inversion (R)
Br
+ Na
Mechanism
Step 1: Loss of
leaving group (slow)
Step 2: Attack of nucleophile
on carbocation (fast)
Can occur from either side of
the flat carbocation
(Path A or Path B)
3
2
Substrate
Substrate
Br
4
1
Rate
Rate
Rate
3
Bonds
Formed
CN
C N
Na
One stereoisomer
inversion
HO
1
4
2
inversion!
This substitution reaction results in an inversion of configuration at C-2
The rate of the reaction is ONLY sensitive to the concentration of
the substrate (and not the nucleophile)
H 2O
Br
+ H 3O Br
Rate Law
Br
Stereochemistry
Substitution occurs with inversion of configuration at chiral centers
OH
3
SN1 vs. SN2 Summary
δ
N C
–
H
δ
+ δ–
Br
partial bonds!
Transition state
H
N C
2
1
3
4
(R)
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• Explains bimolecular rate law (depends on conc. of nucleophile and substrate)
• Explains inversion of stereochemistry
• Explains sensitivity to steric hindrance (bulky groups slow down backside attack)
This is called the SN2 mechanism
(Substitution, Nucleophilic, bimolecular)
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