Elimination Continuum

8/3/2019 Elimination Continuum

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Chap 10. Elimination Reactions

-elimination (1,2-elimination)

-elimination (1,1-elimination)

possible mech.

CH C L + B-

+ B H + L-

CH2CH2Br CH CH2 + EtOHEtO

-/EtOH

C C L

H

+B- + B H + L

-

C C

Cl

Cl

HCCl3 + OH-

H2O + C Cl Cl-

+ CCl2

CH CH2NH3C

H3C

CH3

CH3

CH3

+ OH-

C CH2

H3C

H3C

C N

H3C

H3C

CH3

CH3

CH3

OHH

CH2 C CH2

H3C

H3C

C NH3C

CH3

OH

H

CH

H

C NH3C

CH3

H

CH CH3C

CH3

H

CH C CH2

H3C

H3C

C NH3C

CH3

CH3

CH3

CH3

H

CH2 C NH3C

CH3

CH2

CH3

CH3

H

CH2

OH

C CH2

H3C

H3C

2-

-

,-

differentiate

by D-labelin

a deuterium label on-carbon allows differentiation of thethree mech.

if D appears on alkene-elimination

if D appears on ,-elimination

if D not on alkene, not on amine-elimination

N

CH2D

CH3

CH3


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1,2-elimination

differ in the timing of bond cleavage and/or the

presence of intermediate

More-OFerrall diagram

the T.S. of E2 can shift towar

E1-like on E1cb-like, dependin

on structure & reaction medium

e.g. stronger base or poore

leaving gpshift to E1cb

Good LG, or high ionizin

solvent shift to E1

carbanionintermediate

carbanion intermediate

E2

second order kinetics

rate = k[B-][R]

E1, first order kinetics

r.d.s. the unimolecular

ionization

rate =k

[R]

E1-like

E1cb-like


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For E1cb, an intermediate carbanion is involved

B- + RH BH + R

-k1

k-1

Pk2

21

12

112

][

]][[][

]][[]][[][..

kBHk

BHRkkR

RHBkBHRkRkass

+

=

=+

21

122

][]][[][

kBHkBHRkkRk

dtdPrate

+===

Characteristic for substrates with acidic -H, or poor leaving

group, or having electron-withdrawing group on -C.

ifk1 >>k-1, k2, and [B-]>>[RL].

Pseudo first order, all RL is in the form of carbanion

Rate k[RL](first order)

characteristicsfast isotope exchange of C-DkH/ kD~1, appreciable leaving group effect

(element effect)

ifk-1 ~k1, k-1 [BH] >>k2,

if BH is the solvent

If [B-]/[BH] is kept constant using buffer, rate is independent of

the concentration of base specific base catalysis

characteristicsC-H exchange kH/ kD~1, small leaving groupeffect

]][[][

]][[Rate1

12RLBk

BHk

BRLkkobs

==

E1cbR(reversible)

E1cb(anion)


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E1cbip(ion pair)

ifk2 >>k-1 [BH] >>k1Rate k[RL][B-](second order)

characteristicslittle C-H exchangesignificant kH/ kD (2~8)

ion pair

Similar to E1cbR, but no free anion is formed, an ion pair is

formed with the protonate base as the counter cation

aracteristics: kH/kD ~1-1.2. No -H exchange. addition of R3N+DX-

ill not affect the rate and caused no isotope exchange.(so, diff. from E1cbR

E1cbI(irreversible)


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barrier to

1,2-elim.

inversion

Stereochemistry of 1,2-Elimination Rxns

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

parallel p-orbitals allow -bond formation during bond

cleavage

incipient bond

more carbanion

character

(2) torsional strain

(3) electrostatic repulsion


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preference for anti-elimination

H

H

Cl

H

H

H

Cl

H

ClCl

ClCl

Cl

Cl

Cl

Cl

Cl

H

- HCl

anti-elimination

impossible

H

H

Cl

H

H

Cl

H

H

ClCl

ClCl

Cl Cl

Cl

Cl

Cl

H

- HCl

antipossible

H

CH3

H

Cl

Cl

H

H

H3C H

H3C

CH3CH2O

-

CH3CH2OH

anti

H3C H

(E) only syn-product

H

CH3

Cl

H

Cl

H

H3C

H

H3C H

CH3CH2O

-

CH3CH2OH

anti H

H3C

(Z) only syn-product

Cl

H

H

Cl

- HCl

anti-impossiblesyn-possible

H

Cl

H

Cl

H

Cl

- HClanti-impossible

syn-impossible

H

Cl

(anti-clinal)

H

HCl

Cl

k=1- HCl

Cl

Cl

HCl

H

k=7.8syn- - HCl

Cl

(anti-clinal)

k

10-4

1

k

85

1

syn is more favored than anti-c


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Syn-elimination can proceed in acyclic system

due to steric effect

CH

R

CH2N

CH3

CH3

CH3

OH-/50%DMSO-H2O

C

R

C

H

H

R=H < 5% syn-R=CH3 26.5% syn-elim.R= 68.5% syn-elim.CH3H

CH3

O

3PCH2 CH2

CH2Br

BrCHB

- HBr

separation Br

H

1.)t-BuLi

2.)D2O

D

H

BH3

D

H

H OH

1.)TsCl

2.)HN(CH3)23.)CH3Br

D HH

N(CH3)3 Br-

H

D

D

H

syn

anti

Br2

threo

stereospecificallylabelled substrate

H

R

N H

R

N

B

B anti syn

steric hindrance

= 3.02 = 3.69

eclipsing

effect


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Syn-elimination can be promoted through a cyclic transition

state with metal complex

CH CH

Cl Cl

t-BuOK/t-BuOH

H

Cl

H

Cl

B

Cl H

H Cl

Cl

H

B K

-

-

anti

syn

87%

Cl

H

13%

meso-

N

H3C CH3

CH33-ene 2-ene

+

cis-trans isomer

H

RH

R

X

H

B

H

HR

R

X

H

B

trans cis

X = halide trans

X = OTs cis increas

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

9.43-eneNaOH-H2O

53.03-eneNaOH-DMSO

803-enet-BuOK

673-enesec-BuOK

203-eneMeOK

Syn, %Rxn prod.Condition

the stronger the bas

the higher amt. of

Syn-elimination


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Effect of leaving gp

better leaving gp, syn-elimination, anti-elimination favored

polar solvent stablize the leaving gp favor anti-eliminationnon-polar solvent favor ion-pair and complexed T.S

C C

D

XC4H9

C4H

9

H

H

C C

C4H9

C4H9D

H

+ C C

H

C4H9C4H9

H

CC

C4H9

C4H9 H

H

+ C C

D

C4H9C4H9

H

E-product Z-product

E-product Z-product

anti

syn

Y CH2CH2X + EtO-

Y CH CH2

3.772.752.272.14

2.985.075.677.11kH/kD

+NMe3+SMe2OTsBrX =

more negative charge

accumulation on C

more than half-transferre

BHC-

% syn elimination

BenzeneDMSOBenzeneDMSO

Z productE productleaving gp

84769293+N(CH3)3

164274OTs

397626Cl


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Regiochemistry in 1,2-Elimination

more substituted olefin is more stable,

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

The TS more like carbanion, the

stability of carbanion determine

the product distribution

E1cb-like rxn less substituted olefi

aytzeff

rxn

ffman

rxn

Saytzeff rule

Hoffman rule

(onium cpds)

IEtO

-

EtOH

82%

more subtituted18%

CH2CH2CH2 N

CH3

CH2CH2

CH3

OH-

+

+

98%

less subtituted

2%

S

H3C CH2EtO

-

+

74%

less subtituted26%

True for good leaving gp, eg. Br, I, OT


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Interpretation of Hofmann mechanism

Inductive effect

the inductive is important

if the C-H bond breaking

is leading C-L breaking E1cb-like

-CH2CH2Br = 2.1

-CH2CH2+S(CH3)2

= 2.6 ( more anion-charater on C, more E1cb-like )

Steric effect

increasing size of alky gp

on C will increase the

amt. of Hofmann product

Effect of Leaving group

R CH2 C

Br

CH3

CH3

baseRCH2

CH2

CH3

R CH3

CH3H

1-olefin 2-olefin

H

CH

H

C

N

H

C C

H

H

H

H

H

more acidic less acidic

e-withdrawing gp

H

CH

H

C

N

C C

H

H

H

H

H

leaving gp

more accessible less accessible

t/c% cis-hexene% trans-2-hexene% 1-hexeneX

3.017.954.527.6Br

2.917.149.533.3Cl

2.39.121.069.9F

inc.poor

aving

mall

X

+NaOCH3

by EtO-by pyridine

8670t-Bu5444

5032C2H5

3025R= CH3


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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 developingcarbocation 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, poorleaving gp makes rxn more E1cb-like.

*More electronegative leaving gp makes TS less carbocation

character on -carbon and more carbanion character on-carbon atom.

Elimination Continuum

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