Elimination reactions: E1, E2

E2: biomolecular elimination

H
B:-
C C C C BH X:-
X

Reverse of H-X addition

Need an α proton
if more than one, product mixture results

kinetics: rate = k[RBr][B:-]

H3 C Cl
H B:- +
C C
H loss of a loss of b
H CH3 (minor) (major)
b a

CH 3 CH 3
CH 3
H a - H
B:
+
H
H H
Br
H H H H H
b
loss of a loss of b
(major) (minor)

Zaitsev’s Rule: In general, for base promoted elimination

reactions, the more highly substituted alkene is the major product.

1
 c NaOEt
a
lose a
EtOH
Br b

lose b

lose c
major

Chiral substrate

+ - H H Et H
Na OEt Ph
C C C C -
EtOH EtOH Br
Et
H3C Br
H3C Ph
R S (E)
100%

-
OEt H H
Ph
C C Ph = C6 H5
Et Et = C2 H5
H 3C Br

2
 H Br H
Anti-periplanar conformation preferred H Ph
•to reduce steric strain. H
•maximize developing π overlap Et CH3 Et CH3
Br Ph
-
B: anti syn

-
B: H H
H Ph H
Ph Et H
Et H3 C Ph
Et H 3C
H3 C Br
Br
-
δ
B:- H3C H
Ph H3C H
Et Ph H3 C H
Et
Et Ph
H Br H Br

B: - δ- Notice closer approach of

B:- to developing Br- ion.

E2: substrate requirement summary

• α proton must be present
•must achieve anti-periplanar conformation

B: -
H H
C C H
C C Et
Et Br rotate Et
H3 C H C C
H3 C Br H3C H
R,R (Z)
anti-periplanar
one α proton
not peri-planar

3
 E2: leaving groups

-
:B
H Transition state
•leaving group is developing negative charge
C C •good leaving groups are weak bases

X
δ−

E2: Base/solvent combination (nucleophile)

Prevalent elimination mechanism when a strong base is used in
combination with its CA as solvent.

OH- / H2O O- / OH O-
/ OH

useful when α-proton is not very acidic

Elimination reactions and cyclohexane conformation

O- Na +
FAST

OH
cis [α]D = 0
Br racemic

O-Na +
SLOW

trans OH [α]D = 0
Br racemic
Substrate requirements
Why the difference in rate? • α-proton
•anti-periplanar arrangement

4
 Consider chair conformations: bigger group wants to be in equatorial position

cis H H

4 6
5 H -
RO
H
2 ROH
3 1
H H
5 6 Br
H H 50/50
1
4 2 H anti-periplanar (poised for E2)
3
H Br RO-
Br
trans H H

4 6 H
5 H
H
Br small fraction
2 ring flip
3 1
H H Br
H H
5 6 H H
H Br
1 Leaving group must be in
4 2 H H
H
H 3 H axial position for E2. H

Rationalize:
Br
EtO- FAST
EtOH
Et Et Et
cis major minor Zaitsev's
Rule
Br
EtO- SLOW
EtOH
Et Et
trans

Br
H ethyl is larger than Br, so
H EtO - takes equatorial position
Et EtOH in most stable conformer
Et Et
bH (a) (b)
Ha
H H axial
Et
Br H EtO-
Et H EtOH
Et
H eqH Br

5
 Summary of E2 requirements

substrate
• α-proton
•anti-periplanar (trans diaxial H, LG)

LG
•weak base

B:-/solvent
•strong/conjugate acid

An aside: How do we know which step is rate determining?

Isotope Effects--changes in the rate resulting from the use of different isotopes.
• 2 H or D, deuterium, most commonly used
•C-D bond is slightly stronger, so Eact is greater
•if breaking C-H bond is r.d.s., substitution with D will result in slower rate
rel. rate
CH4 + Cl . CH3Cl + HCl 12
CD4 + Cl . CD3Cl + DCl 1
H H H

H C H + Cl . H C H Cl H C . + HCl

H H H
bond breaking occurs in transition state
H
-
EtO
C CH2Br CH CH2 Faster
EtOH
supporting H
evidence D
for E2 EtO
-
C CH2Br CD CH2 Slower
EtOH
D

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 E1: unimolecular elimination reaction

H H H
+ B:
C C C C δ+ C C C C BH+
slow fast
X δ− X-
X
E1
B:

H B+
rate = k[RX]
SN 1
C C

Usually get mixture of products.

SN 1 and E1 share common carbocation
B: is too weak to remove α-proton but the
carbocation increases its acidity.

Not very useful for synthesis; usually a side-reaction in SN 1 reactions.

SN 1 and E1 share common carbocation intermediate:

H H H
+ B:
C C C C δ+ C C C C BH+
slow fast
X δ− X-
X
E1
B:

TS1 H B+
TS2 TS2 S N1
C C
E1
I
∆Go S N1

rxn progress

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Some examples:
H H
CH 3 CH3 CH3
Cl OCH 3
CH 3OH +
H
o H
3 E1 S N1

H HO CH3
H H Cl - + CH
O 3
CH 3 + CH 3
Cl SN1 CH3
HOCH3 fast
slow H
H
E1
fast

CH 3 CH3
+
H O CH 3 OCH 3 +
+ + H O CH3
H H

Br H b minor major
H2O OH
H
H3C
CH3 CH3
a a a b
E1 SN1
Br H
+ H
Br-
slow
H H OH2
H
E1
SN1
+OH OH
2 H2O
+ H3 O+
+ + H 3O
+

8
 E1 summary
substrate
• α-proton
•anti-periplanar not required
leaving group
•weak base
base = solvent
weak bases
neutral species with electron pair

Distinguishing between SN1, SN2, E1, E2

substrate, base/nucleophile

cannot form stable carbocation

•no E1
1o substrates: SN2, E2 •no SN 1

good Nu α-proton, anti-periplanar

•strong base
•polarizable
(increases going
down a group)

9
 -
S N2 Cl I I
+ Cl-
DMSO

polar aprotic solvent

O-
E2 Cl
O
OH
E2 SN 2
(trace)

t-butoxide is a very strong base, so excellent nucleophile

but: SN 2
•steric bulk of t-butoxide disfavors SN 2 H H
(easier to pluck off a proton) - E2
H
O
•t-butanol is a poor SN 2 solvent (polar protic) C C
H
H3C Cl

3o substrates (SN 1, E1 or E2): do not react by S N2!

strong bases
weak bases α-proton, anti-periplanar

weak base
CH3 CH3
OH O
H3C C Br H2C C +
slow
CH3 CH3
E1 SN1

CH3

H3C C +

CH3

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Strong Base

CH 3 CH 3
O-
H3C C Br H 2C C OH Br -
OH
CH 3 CH 3
E2

H CH 3
O- CH 3 OH H CH 3
C C C C
H
Br H CH3
H
Br-

SUMMARY
Use substrate and base/Nu to distinguish pathways!

1o substrates: SN2, E2

good Nu strong base

α-proton, anti-periplanar

3o substrates (SN1, E1 or E2)

strong bases
weak bases
α-proton, anti-periplanar

2o substrates: difficult to predict, can react by all 4 pathways!

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