SN2 Reactions – Relative Rates of Reactions
Nucleophile
Relative Rate
CH3OH
1
NO3 -
slowest rxn, weak Nu:
32
F-
500
O
||
CH3C–O -
20,000
Cl ..
Et2S:
H3N:
23,500
219,000
316,000
Br –
617,000
CH3O –
..
Me2Se :
1,950,000
N≡C: –
.. _
Et2As:
5,010,000
2,090,000
7,940,000
I-
26,300,000
HS-
100,000,000
fastest rxn, strong Nu:
SN2 Reaction Mechanism
Walden Inversion
.. HO:
H
H
C
Br
RH
Nucleophile
HO
C
H
Br
C
R
Product
SN2 transition state
center carbon is planar
Nu and LG are linear
+ Br
H
RH
Electrophile
backside attack
HO
Leaving
Group
SN2 Nucleophile Strength – Effect of Charge
Nucleophile
Relative Rate
CH3OH
1
Adding negative
CH3O1,950,000
Et2S :
EtS-
219,000
100,000,000
charge increases
nucleophilicity
SN2 Reactions – Effect of Size
Nucleophile
Relative Rate
EtOH
1
Et2S :
219,000
Et2Se :
2,090,000
FCl Br I-
Moving down the
periodic table
increases
nucleophilicity
500
23,500
617,000
26,300,000
SN2 Reactions – Periodic Effects
Nucleophile
Relative Rate
F500
CH3O1,950,000
H2N: 4,560,000
Moving to the left on
the periodic table
increases
nucleophilicity
Effect of Leaving Group
Key Factors for Reaction Mechanisms
Chem 241
SN2 Reactions:
*1. Sterics – substrate (alkyl halide) must not be highly hindered
no SN2 reactions at tertiary centers; primary works the best
*2. Nucleophile – must have a good nucleophile, such as phosphorus, sulfur, nitrogen,
or negative oxygen
(no SN2 with H2O or ROH)
3. Leaving Group – good leaving group helpful
4. Solvent – polar solvent helpful
examples: DMSO, DMF
SN1 Reactions:
*1. Substrate – must form a stable carbocation (3°, allylic, benzylic;
*2. Solvent – polar, protic solvent (such as ROH or H2O) important
2. Leaving Group – good leaving group important
4. Nucleophile – any mild nucleophile will work
(powerful base/nucleophile will lead to E2/SN2)
maybe 2°)
E2 Reactions:
*1. Hydrogen – must have a hydrogen next door (β) to the leaving group to form an alkene
(beta hydrogen required)
*2. Base – must use a strong base; hindered base also helpful to avoid SN2;
t-butoxide should always give E2
3. Leaving Group – good leaving group helpful
E1 Reactions:
*1. Substrate – must form a stable carbocation (3°, allylic, benzylic; maybe 2°)
2. Base – weak base will help promote E1 over SN1
examples: carbonate (CO32-), acetate (CH3CO2-), amines
3. Solvent – polar, protic solvent important
examples: water, alcohols
4. Leaving Group – good leaving group important (-Br, -I, -OTos)
Chem 241
Flow Cha rt for SN2 / E2 / SN1 / E1 Rea ctio n Mecha nisms
Is there a powerful base/nucleophile present?
( negatively charged C, N, O, S, or P )
Yes
Then no SN1 or E1 reactions
No
(C+ not possible)
Then no E2 reactions
Is the substrate hindered?
Yes
?
(3°)
(2°)
E2 Rxn
Mech
Can a stable carbocation form?
No
(1°)
SN2 Rxn
Mech
Yes
No
(3°, allylic,
benzylic)
Then SN1 or E1 mechanism
(polar solvent also needed)
Is there a weak base present?
Type of base/nucleophile
Strong Base
( RO- R2N- )
E2 Rxn
Mech
Strong Nucleophile
( RS- R2P- )
SN2 Rxn
Mech
2-
-
( CO3 , RCO2 , R3N: )
Yes
E1 Rxn
Mech
favored
(1°, most 2°)
No SN1/E1
Is there good nucleophile?
( R3N, R2S, R3P, I- )
No
Yes
SN1 Rxn
Mech
favored
SN2 Rxn
Mech
No
No Rxn
Notes: All reactions require a good leaving group.
E2 elimination reactions must have a hydrogen atom next door (β hydrogen)to the leaving group: H-C―C-X.
t-Butoxide always does E2 eliminations and always gives the least substituted alkene. Other bases give the most substituted alkene.
The E1/SN1 reaction mechanisms often lead to mixtures.