Chap 10. Elimination Reactions
β-elimination (1,2-elimination)
H
C
C
ψ
-
+ B
L
α
β
EtO-/EtOH
CH2CH2Br
α
β
ψ
CH
C
C
α-elimination (1,1-elimination)
+ BH + L
EtOH
+
CH2
-
H
B- +
C
HCCl3
+ OH-
C
L
α
β
CH
CH2N
H2O +
C
H3C
+ OH
β2-
C
+
CCl2
C
CH2
H3C
OH
H
Cl
H3C
-
CH3
possible mech.
-
Cl
Cl
CH3
H3C
+ BH + L-
Cl
CH3
H3C
α
β
CH3
N
CH2
H3C
H3C
CH3
C
CH3
CH2
H3C
OH
H
α-
H
H3C C
CH
H
H
H3C C
N
CH3
N
CH
H3C C
CH3
H3C
CH
CH3
C
H3C
differentiate
by D-labeling
OH
H
α’,β-
H3C C
H
CH3
CH2 N
CH3
CH3
H3C C
CH3
CH3
CH2
CH2 N
H3C
CH3
CH3
CH2
C
CH2
H3C
a deuterium label on β-carbon allows differentiation of the
three mech.
if D appears on alkene → α-elimination
if D appears on
CH2D
N
CH3
CH3
→ α’,β-elimination
if D not on alkene, not on amine → β-elimination
1,2-elimination
differ in the timing of bond cleavage and/or the
presence of intermediate
More-O’Ferrall diagram
carbanion
intermediate
‡
E1cb-like
‡
‡
E1-like
‡
‡
‡
‡
carbanion intermediate
the T.S. of E2 can shift toward
E1-like on E1cb-like, depending
on structure & reaction medium
e.g. stronger base or poorer
leaving gp Æshift to E1cb
Good LG, or high ionizing
solvent Æ shift to E1
E2
second order kinetics
rate = k[B-][R]
E1, first order kinetics
r.d.s. the unimolecular
ionization
rate = k [R]
For E1cb, an intermediate carbanion is involved
B + RH
k1
k-1
-
BH + R
k2
P
k2 [ R − ] + k−1[ R − ][ BH ] = k1[ B − ][ RH ]
k2 ⋅ k1[ R − ][ BH ]
−
[R ] =
k−1[ BH ] + k2
dP
k2 ⋅ k1[ R − ][ BH ]
−
rate =
= k2 [ R ] =
dt
k−1[ BH ] + k2
s.s.a
Characteristic for substrates with acidic β-H, or poor leaving
group, or having electron-withdrawing group on β-C.
E1cb(anion)
if k1 >>k-1, k2, and [B-]>>[RL].
Pseudo first order, all RL is in the form of carbanion
Rate
k[RL](first order)
characteristics：fast isotope exchange of Cβ-D
kH/ kD~1,
appreciable leaving group effect
(element effect)
≈
E1cbR(reversible)
if k-1 ~k1, k-1 [BH] >>k2,
k2 k1[ RL][ B − ]
Rate =
= kobs [ B − ][ RL] if BH is the solvent
k−1[ BH ]
If [B-]/[BH] is kept constant using buffer, rate is independent of
the concentration of base ⇒ specific base catalysis
characteristics：Cβ-H exchange kH/ kD~1, small leaving group
effect
E1cbip(ion pair)
Similar to E1cbR, but no free anion is formed, an ion pair is
formed with the protonate base as the counter cation
ion pair
characteristics: kH/kD ~1-1.2. No β-H exchange. addition of R3N+DXwill not affect the rate and caused no isotope exchange.(so, diff. from E1cbR)
E1cbI(irreversible)
if k2 >>k-1 [BH] >>k1
Rate
k[RL][B-](second order)
characteristics：little Cβ-H exchange
significant kH/ kD (2~8)
≈
Stereochemistry of 1,2-Elimination Rxns
incipient bond
parallel p-orbitals allow πbond formation during bond
cleavage
barrier to
1,2-elim.
anti-elimination is favored over syn due to (1) overlap of electron
in Cβ-H bond (HOMO) with backside of C-L bond (LUMO)
if carbanion formation is extensive → syn-elimination is possible
after inversion of carbanion
more carbanion
character
(2) torsional strain
(3) electrostatic repulsion
inversion
preference for anti-elimination
H
Cl
H
Cl
ψ
H
anti-elimination
impossible
Cl
H
H3C
≡
Cl
ψ
H
H
ψ
H3C
Cl
CH3CH2O
ψ
H
H
H
H
Cl
-
anti
ψ
H3C
ψ
H
(E) only
ψ
CH3CH2O-
H
ψ
ψ
syn-product
H
H3C
ψ
ψ
ψ
ψ
CH3CH2OH
anti
(Z) only
H
H3C
H3C
Cl
H
1
Cl
H
CH3CH2OH
Cl
≡
Cl
Cl
anti
possible
H
CH3
10-4
Cl
Cl
Cl
- HCl
H
H
Cl
ψ
H
Cl
Cl
Cl
CH3
H
Cl
Cl
- HCl
k
H
H
Cl
Cl
Cl
Cl
H
Cl
H
ψ
Cl
H
Cl
ψ
H
- HCl
anti-impossible
syn-possible
H
Cl
Cl
(anti-clinal)
H
syn-product
k
85
H
Cl
H
Cl
H
Cl
Cl
- HCl
anti-impossible
syn-impossible
Cl
1
Cl
H
k=1
- HCl
Cl
H
H
(anti-clinal)
Cl
H
Cl
k=7.8
syn- - HCl
syn is more favored than anti-clinal
Syn-elimination can proceed in acyclic system
due to steric effect
CH3
ψ
CH
R
CH2N
ψ
CH3
< 5% syn26.5% syn-elim.
CH3
H
CH3
R=
B
C
OH-/50%DMSO-H2O
CH3
R=H
R=CH3
C
H
R
68.5% syn-elim.
anti
syn
R
H
ψ
H
ψ
eclipsing
effect
H N
R
N
B
ρ = 3.02
ρ = 3.69
steric hindrance
ψ
ψ
ψ
O ψ3P─CH2
separation
Br2
CH2
ψ
Br
1.)t-BuLi
2.)D2O
ψ
H
1.)TsCl
2.)HN(CH3)2
3.)CH3Br
H
ψ
D
Br
CH2Br
ψ
- HBr
D
CHBr
H
BH3
ψ
D
H
H
H
ψ
H
syn
-
D
N(CH3)3 Br
threo
stereospecifically
labelled substrate
OH
anti
ψ
D
H
Syn-elimination can be promoted through a cyclic transition
state with metal complex
B
ψ
ψ
meso-
CH
CH
Cl
Cl
H
H
Cl
Cl
t-BuOK/t-BuOH
ψ
δ-
B
ψ
δ-
Cl
H
ψ
H
ψ
Cl
ψ
Cl
H
87%
anti
K
ψ
ψ
H
Cl
ψ
13%
syn
In the presence of 18-crown-6, K+ is complexed by crown ether
→ The 6-membered TS is suppressed, → only anti-product
Effect of Base
+
N CH3
H3C
3-ene
CH3
Condition
NaOH-H2O
NaOH-DMSO
MeOK
sec-BuOK
t-BuOK
2-ene
Rxn prod.
3-ene
3-ene
3-ene
3-ene
3-ene
Syn, %
9.4
53.0
20
67
80
the stronger the base
the higher amt. of
Syn-elimination
cis-trans isomer
X
X
H
R
R
H
trans
R
H
H
B
cis
R
H
H
B
X = halide → trans
X = OTs
cis increase
Effect of leaving gp
C4H9
C
H
X
+
C
H
C
C4H9
C
D
+
C
C
C4H9
C4H9
Z-product
C4H9
E-product
syn
H
H
D
C4H9
C
C4H9
C
anti
H
D
H
C4H9
H
E-product
H
C
C
C4H9
C4H9
Z-product
% syn elimination
E product
Z product
leaving gp
DMSO
Benzene
DMSO
Benzene
Cl
6
62
7
39
OTs
4
27
4
16
93
92
76
84
+N(CH
3)3
→ better leaving gp, syn-elimination↓, anti-elimination favored
→ polar solvent stablize the leaving gp favor anti-elimination
non-polar solvent favor ion-pair and complexed T.S
Y
X=
CH2CH2X
+ EtO
-
Y
Br
OTs
+SMe
2
+NMe
kH/kD
7.11
5.67
5.07
2.98
ρ
2.14
2.27
2.75
3.77
3
CH
CH2
more than half-transferred
B‥‥H‥‥‥C δ
more negative charge
accumulation on Cβ
Regiochemistry in 1,2-Elimination
I
EtO-
+
EtOH
82%
more subtituted
CH3
CH2CH2CH2
N
CH2CH2
OH-
H3C
CH2
S
+
∆
CH3
98%
less subtituted
EtO-
Saytzeff rule
18%
2%
Hoffman rule
(’onium cpds)
+
26%
74%
less subtituted
more substituted olefin is more stable,
Saytzeff
rxn
TS leading to more stable product
will have lower activation energy
“ if ” the TS has character of product
i.e. E1, E2
product relative stability determine the
product distribution
True for good leaving gp, eg. Br, I, OTs
Hoffman
rxn
The TS more like carbanion, the
stability of carbanion determine
the product distribution
E1cb-like rxn → less substituted olefin
Interpretation of Hofmann mechanism
e-withdrawing gp
Inductive effect
N
H
H
H
H
C
C
C
C
H
H
H
H
H
the inductive is important
if the C-H bond breaking
is leading C-L breaking
→ E1cb-like
more acidic
less acidic
ψ-CH2CH2Br
ψ-CH2CH2+S(CH3)2
ρ = 2.1
ρ = 2.6 ( more anion-charater on Cα,
→ more E1cb-like )
leaving gp
Steric effect
N
H
H
H
C
β
Cα
C
H
β
H
H
more accessible
Br
R
CH2 C
C
H
H
less accessible
base
CH3
increasing size of alky gp
on Cβ will increase the
amt. of Hofmann product
CH3
CH2
t-Bu
CH3
H
CH3
RCH2
CH3
1-olefin
R= CH3
C2H5
R
2-olefin
by pyridine
25
32
44
70
by EtO30
50
54
86
Effect of Leaving group
NaOCH3
+
X
small
poor
leaving
gp
X
F
Cl
Br
I
% 1-hexene
69.9
33.3
27.6
19.3
% trans-2-hexene
21.0
49.5
54.5
63.0
% cis-hexene
9.1
17.1
17.9
17.6
t/c
2.3
2.9
3.0
3.6
inc.
Summary of Trends
The transition state structure determines the product distribution
The transition state (E1, E2, E1cb ) is affected by reactant
structure, solvent, base, …
*α-aryl (or alkyl ) substituent can stabilize a developing
carbocation and make TS more E1-like
*β-aryl substituent can stabilize carbanion at β-carbon and
make TS more E1cb-like
*Introducing a β-alkyl gp makes the reaction more E1-like
(less E1cb-like ). (Shift a E1cb to more synchronous, and
more E2-like, shift a E1-like more E1-like )
*Better leaving group makes reaction more E1-like, poor
leaving gp makes rxn more E1cb-like.
*More electronegative leaving gp makes TS less carbocation
character on α-carbon and more carbanion character on
β-carbon atom.