Chap 10.

Elimination Reactions
β-elimination (1,2-elimination)
- -
H C C L + B α + BH + L
β α β

EtO-/EtOH
ψ CH2CH2Br ψ CH CH2 + EtOH
α-elimination (1,1-elimination)
H
B- + C C L C C + BH + L-
β α β α

Cl
HCCl3 + OH- H2O + C Cl Cl
-
+ CCl2
Cl
H3C CH3
H3C
CH CH2N CH3 -
+ OH C CH2
H3C CH3 H3C
possible mech.
OH
H CH3
H3C H3C
β2- C CH2 N CH3 C CH2
H3C CH3 H3C
OH
H H H H
H3C
α- H3C C CH N H3C C CH N H3C C CH C CH2
CH3 CH3 CH3 H3C
OH differentiate
H
CH3 H
CH2 H3C
by D-labeling
α’,β- H3C C CH2 N CH3 H3C C CH2 N CH3 C CH2
CH3 CH3 CH3 CH3 H3C

a deuterium label on β-carbon allows differentiation of the

three mech.
if D appears on alkene → α-elimination
CH2D
if D appears on N CH3 → α’,β-elimination
CH3
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 ‡ E1cb-like
intermediate ‡
‡ 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 E1, first order kinetics

second order kinetics r.d.s. the unimolecular
rate = k[B-][R] ionization
rate = k [R]
 For E1cb, an intermediate carbanion is involved
k1 -
k2
- P
B + RH BH + R
k-1
s.s.a　　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
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+DX-

will 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 π-
bond 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 inversion

character

(2) torsional strain

(3) electrostatic repulsion

 preference for anti-elimination
H k
Cl H Cl
Cl Cl
Cl H Cl
Cl - HCl
10-4
H Cl anti-elimination Cl
Cl Cl
impossible H
H
H H
Cl
Cl
Cl Cl
Cl H - HCl Cl Cl
H
Cl
H Cl
Cl
Cl 1
H anti H
Cl H possible
ψ CH3
≡ H3C Cl
-
H3C ψ H3C H
H ψ ψ CH3CH2O
H CH3CH2OH
H
H ψ anti ψ H ψ ψ
Cl
ψ (E) only syn-product
CH3 Cl
≡ H3C H3C ψ
H3C H
ψ CH3CH2O-
ψ H ψ CH3CH2OH
H H
H anti ψ ψ ψ H
(Z) only syn-product
Cl
H - HCl H k
anti-impossible
H syn-possible
85
Cl Cl (anti-clinal)
H
Cl - HCl H
anti-impossible
H syn-impossible
1
Cl Cl Cl Cl
Cl H
H
k=1
- HCl (anti-clinal)

Cl Cl
H 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

ψ CH3 ψ H
CH CH2N CH3 C C
OH-/50%DMSO-H2O
R CH3 R H
R=H　　　　　　　　　　< 5%　syn-
R=CH3　　　　　　　26.5%　syn-elim.
CH3
R=　　　　　　　　
H 　68.5%　syn-elim.
CH3

B anti syn
R
H ψ
eclipsing
effect H N
ψ R
N B
ρ = 3.02 ρ = 3.69
steric hindrance

ψ ψ ψ Br ψ
O ψ3P─CH2 CH2 Br2 CH2Br - HBr CHBr

ψ Br ψ D H OH
separation 1.)t-BuLi BH3 ψ
2.)D2O D
H H H

H D ψ H
1.)TsCl ψ H
2.)HN(CH3)2 syn
3.)CH3Br -
N(CH3)3 Br D
anti
threo ψ D
stereospecifically
labelled substrate
H
 Syn-elimination can be promoted through a cyclic transition
state with metal complex B
ψ ψ H H ψ ψ
t-BuOK/t-BuOH ψ
meso- CH CH
ψ Cl
Cl Cl Cl Cl H
anti 87%
δ-
B K
δ-
H Cl ψ H

ψ H
Cl ψ
Cl ψ
syn 13%

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
3-ene 2-ene
H3C CH3

Condition Rxn prod. Syn, %

NaOH-H2O 3-ene 9.4
the stronger the base
NaOH-DMSO 3-ene 53.0 the higher amt. of
MeOK 3-ene 20 Syn-elimination
sec-BuOK 3-ene 67
t-BuOK 3-ene 80
cis-trans isomer
X X
H R R H
trans cis
R H R H
H H X = halide → trans
B B X = OTs cis increase
 Effect of leaving gp
C4H9 H H H

anti C C + C C
D H D C4H9 C4H9 C4H9
C4H9 E-product Z-product
H C C

C4H9 X H C4H9 D H
syn
C C + C C
C4H9 H C4H9 C4H9
E-product Z-product

% syn elimination
leaving gp E product Z product
DMSO Benzene DMSO Benzene
Cl 6 62 7 39
OTs 4 27 4 16
+N(CH
3)3 93 92 76 84

→ 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 CH2CH2X + EtO Y CH CH2

X= Br OTs +SMe
2
+NMe
3
more than half-transferred
kH/kD 7.11 5.67 5.07 2.98 B‥‥H‥‥‥C -
δ
ρ 2.14 2.27 2.75 3.77
more negative charge
accumulation on Cβ
 Regiochemistry in 1,2-Elimination
I
EtO-
+
EtOH Saytzeff rule
82% 18%
more subtituted
CH3
OH-
CH2CH2CH2 N CH2CH2
∆
+ Hoffman rule
CH3 98% 2% (’onium cpds)
less subtituted
H3C CH2
S EtO-
+
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
the inductive is important
H C C C C H if the C-H bond breaking
H H H H 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 )
Steric effect leaving gp
N
H H H increasing size of alky gp
H C
β
Cα C
β
C H on Cβ will increase the
H H H amt. of Hofmann product

more accessible less accessible

Br CH2
R CH3
base
R CH2 C CH3 RCH2
CH3 H CH3
CH3
1-olefin 2-olefin
by pyridine by EtO-
R= CH3 25 30
C2H5 32 50
44 54
t-Bu 70 86
Effect of Leaving group
NaOCH3
+
X
X % 1-hexene % trans-2-hexene % cis-hexene t/c
small
F 69.9 21.0 9.1 2.3
poor Cl 33.3 49.5 17.1 2.9
leaving Br 27.6 54.5 17.9 3.0 inc.
gp I 19.3 63.0 17.6 3.6
 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.