Chap 10.

Elimination Reactions
] -elimination (1,2-elimination)
H C
]

C
\

+ B

+ BH + L CH2 + EtOH

-elimination (1,1-elimination)
H
\

CH2CH2Br

EtO-/EtOH

CH

B +

C
]

C
]

C
\

+ BH + L-

HCCl3

+ OH-

Cl H2O + C Cl Cl Cl
-

CCl2

H3C CH H3C CH2N

CH3 CH3 CH3

H C H3C H H CH N CH2 OH N

H3C + OH
-

C H3C

CH2

possible mech.
H3C

CH3 CH3 CH3

H3C C H3C H H3C C CH3 OH CH N H H3C C CH3 H H3C C CH3 CH2 N CH2 CH3 CH3 H3C H3C C CH H3C CH2

2-

OH

H3C C CH2

H3C C CH3 H

,] -

CH3 CH2 N CH3 CH3

differentiate by D-labeling

H3C C CH3

CH2

a deuterium label on ] -carbon allows differentiation of the three mech. if D appears on alkene \ -elimination if D appears on
CH2D CH3 CH3 N

,] -elimination -elimination

if D not on alkene, not on amine ]

1,2-elimination

differ in the timing of bond cleavage and/or the presence of intermediate More-OFerrall 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 shift to E1cb Good LG, or high ionizing solvent 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

k2 [ R ] + k1[ R ][ BH ] = k1[ B ][ RH ] k k [ R ][ BH ] [R ] = 2 1 k1[ BH ] + k2 dP k2 k1[ R ][ BH ] rate = = k2 [ R ] = dt k1[ BH ] + k2 s.s.a

Characteristic for substrates with acidic -H, or poor leaving group, or having electron-withdrawing group on -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) characteristicsG fast isotope exchange of C] -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 k1[ BH ] If [B-]/[BH] is kept constant using buffer, rate is independent of the concentration of base specific base catalysis characteristicsG C] -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 -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) characteristicsG little C] -H exchange significant kH/ kD (2~8)

Stereochemistry of 1,2-Elimination Rxns

incipient bond

parallel p-orbitals allow k bond formation during bond cleavage

barrier to 1,2-elim.

anti-elimination is favored over syn due to (1) overlap of electron in C] -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

inversion

(2) torsional strain (3) electrostatic repulsion

preference for anti-elimination

H Cl Cl Cl H Cl Cl H H H H H H Cl H Cl Cl H
- HCl

Cl

H Cl Cl
- HCl

Cl Cl Cl Cl Cl H

k 10-4

anti-elimination impossible

Cl

Cl

Cl Cl Cl H

Cl

r
H

Cl

anti possible
Cl
CH3CH2O anti
-

CH3 H

r
CH3 H

H3C H

H3C

r
H

H3C

r r

Cl

r
Cl H

CH3CH2OH

r
(E) only H3C

r
H3C

r r

syn-product H

H3C H
Cl H H

CH3CH2OCH3CH2OH anti

r
(Z) only
H Cl

H syn-product

- HCl anti-impossible syn-possible

k 85 1

Cl H Cl H Cl Cl H
k=1 - HCl - HCl anti-impossible syn-impossible

(anti-clinal) H

Cl H

Cl

Cl

(anti-clinal) Cl

Cl H

H Cl
k=7.8 syn- - HCl

syn is more favored than anti-clina

Syn-elimination can proceed in acyclic system due to steric effect

r
CH R CH2N R=H@ R=CH3@ R=@ CH3 CH3 CH3 CH3 H CH3
@ OH-/50%DMSO-H2O < 5%@ syn26.5%@ syn-elim. 68.5%@ syn-elim.

r
C R C

H H

B H

anti

syn

r
R

eclipsing effect H N

l = 3.02

l = 3.69

steric hindrance

r
O r
3PCH2

r
CH2
Br2

Br CH2Br

r
- HBr

CHBr

separation

Br
1.)t-BuLi 2.)D2O

D
BH3

OH D H

H
1.)TsCl 2.)HN(CH3)2 3.)CH3Br

H H
-

r
syn

H D

N(CH3)3 Br

threo stereospecifically labelled substrate

anti

D H

Syn-elimination can be promoted through a cyclic transition state with metal complex B
r r
mesoCH Cl CH Cl B H
t-BuOK/t-BuOH

Cl

r
H 87%

r
K
-

Cl anti

Cl

Cl

r
Cl 13%

r
Cl 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 CH3 3-ene 2-ene

Condition NaOH-H2O NaOH-DMSO MeOK sec-BuOK t-BuOK

Rxn prod. 3-ene 3-ene 3-ene 3-ene 3-ene

X

Syn, % 9.4 53.0 20 67 80

the stronger the base the higher amt. of Syn-elimination

cis-trans isomer
X H R H B R trans H R H B H R H cis

X = halide X = OTs

trans cis increase

Effect of leaving gp
C4H9 D H C4H9 C C X H C4H9 syn anti C D C H + H C C H

C4H9 E-product H C C C4H9 +

C4H9 C4H9 Z-product D C C H

C4H9 H E-product

C4H9 C4H9 Z-product

leaving gp Cl OTs
+N(CH 3)3

% syn elimination E product Z product DMSO 6 4 93 Benzene 62 27 92 DMSO 7 4 76 Benzene 39 16 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
-

CH

CH2

X= kH/kD

Br 7.11 2.14

OTs 5.67 2.27

+SMe 2

+NMe

5.07 2.75

2.98 3.77

more than half-transferred BLL HLLL C

_

more negative charge accumulation on C]

Regiochemistry in 1,2-Elimination
I
EtOEtOH

+ 82% more subtituted 18%

Saytzeff rule

CH3 CH2CH2CH2 N CH3 H3C S CH2

EtO-

CH2CH2

OH

+ 98% less subtituted + 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

The TS more like carbanion, the stability of carbanion determine the product distribution

Hoffman rxn

E1cb-like rxn

less substituted olefin

Interpretation of Hofmann mechanism

e-withdrawing gp

Inductive effect
H H C H

N H C H C H H C H H

the inductive is important if the C-H bond breaking is leading C-L breaking E1cb-like

more acidic less acidic r -CH2CH2Br r -CH2CH2+S(CH3)2 l = 2.1 l = 2.6 ( more anion-charater on C\ , more E1cb-like ) leaving gp Steric effect
N H H C

H C C H

H C H H

increasing size of alky gp on C] will increase the amt. of Hofmann product

CH2

more accessible
Br R CH2 C CH3 CH3 base

less accessible
RCH2

R H 2-olefin

CH3 CH3

R= CH3 C2H5 t-Bu

by pyridine 25 32 44 70

CH3 1-olefin

by EtO30 50 54 86

Effect of Leaving group

NaOCH3 X +

small poor leaving

X F Cl Br

% 1-hexene 69.9 33.3 27.6

% trans-2-hexene 21.0 49.5 54.5

% cis-hexene 9.1 17.1 17.9

t/c 2.3 2.9 3.0

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, *\ -aryl (or alkyl ) substituent can stabilize a developing carbocation and make TS more E1-like

*] -aryl substituent can stabilize carbanion at ] -carbon and make TS more E1cb-like *Introducing a ] -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 \ -carbon and more carbanion character on ] -carbon atom.