1

ELIMINATION REACTIONSELIMINATION REACTIONS

Lecture 13

2

ALKYL HALIDES + WEAK BASE ALKYL HALIDES + WEAK BASE (SOLVOLYSIS)(SOLVOLYSIS)

E1

The removal of a β

-hydrogen becomes difficult without a strong base and a different mechanism (ionization) begins to take place

….. if the substrate is capable.

3

An E1 reaction exhibits first-order kinetics:

rate = k[(CH3

)3

CI]

The E1 reaction proceed via a two-step mechanism.

The bond to the leaving group breaks first before the π

bond

is formed.

The slow step is unimolecular, involving only the alkyl halide.

Mechanisms of Elimination—E1

4

The E1 Elimination Reaction (The E1 Elimination Reaction (two stepstwo steps))

+ :Xslow

fast

B:

C C

+C C

H

C C

H

X

rate = k [RX]

carbocation

unimolecular

Weak base

5

6

The rate of an E1 reaction

increases as the number of R groups

on the carbon with

the leaving group increases.

Mechanisms of Elimination—E1

7

REGIOSELECTIVITYREGIOSELECTIVITY

8

•

E1 reactions are regioselective, favoring formation of the more substituted, more stable alkene.

•

Zaitsev’s rule

applies to E1 reactions also.

Mechanisms of Elimination—E1

THE E1cB MECHANISMTHE E1cB MECHANISM

C C

H

XC C

X

C C

B: protonfirst

halogensecond

carbanion

Elimination, unimolecular, of the conjugate base.Carbanion

mechanism

10

A regioselective

reaction forms more of one constitutional isomer than the other.

A B + C more ‘B’ is formed than ‘C’, where B and C are constitutional isomers.

A stereoselective

reaction forms more of one stereoisomer than the other.

A B+ C more ‘B’ is formed than ‘C’, where B and C are stereoisomers.

Regioselective

and stereselective

reaction

11

A B

C D

‘A’ AND ‘C’ ARE STEREOISOMERS

‘B’ AND ‘D’ ARE STEREOISOMERS

Stereospecific

reaction

In a stereospecific

reaction, each stereoisomeric

reactant forms a different

stereoisomeric

product or a different set of stereoisomeric

products.

12

Alkene

synthesis by elimination reactions

13

Typical acids used in dehydration are sulfuric acid and phosphoric acid

Primary alcohols are most difficult to dehydrate, tertiary are the easiest.

Rearrangements

of the carbon skeleton can occur

Acid Catalyzed Dehydration of Alcohols

14

The temperature and concentration of acid required to dehydrate depends on the structure of the alcohol

Acid Catalyzed Dehydration of Alcohols

15

Only a catalytic amount

of acid is required since it is regenerated

in the final step of the

reactionThe second step

of the E1 mechanism in

which the carbocation

forms is rate determining

Tertiary alcohols react the fastest because they have the most stable tertiary carbocation

- like transition state in the

second step

Mechanism for Dehydration of Secondary and Tertiary Alcohols: An E1 Reaction

16

E1 Mechanism

17

Carbocation

Stability and the Transition State

Recall the stability of carbocations

is:

18

The relative heights of ΔG‡ for the second step of E1 dehydration indicate that primary alcohols have a prohibitively large energy barrier

19

A Mechanism for Dehydration of Primary Alcohols: An E2 Reaction

Primary alcohols cannot undergo E1 dehydration because of the instability of the carbocation-like transition state in the 2nd step.

In the E2 dehydration the first step is again

protonation

of the hydroxyl to yield

the good leaving group water

20

21

E2: Vicinal Dibromides•

Remove Br2

from adjacent carbons.•

Bromines must be anti-coplanar

(E2).

•

Use NaI

in acetone, or Zn in acetic acid.

22

E2: Vicinal Dibromides

23

•

Secondary or tertiary halides•

Formation of carbocation

intermediate

•

May get rearrangement•

Weak nucleophile

•

Usually have substitution products too.

Removing HX via E1

Dehydrohalogenation

of alkyl halides

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25

Removing HX via E2•

Strong base abstracts H+

as X-

leaves from

the adjacent carbon.•

Tertiary and hindered secondary alkyl halides give good yields.

•

Use a bulky base if the alkyl halide usually forms substitution products.

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bromocyclohexane Cyclohexene(93%)

Bromocyclohexane, a secondary alkyl halide, can undergo both substitution and elimination

E2 is favored over substitution using bulky base diisopropylamine

Removing HX via E2

H

H

BrH

H

H

+(iPr)2NH, heat

[(CH3)2CH]2NH2Br

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Formation of Hofmann Product

•

Bulky bases abstract the least hindered H+

•

Least substituted alkene

is major product.

28

Hofmann Elimination•

A quaternary ammonium salt

has a good

leaving group -

a neutral amine.•

Heating the hydroxide salt produces the least substituted

alkene.

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30

Hofmann Elimination

31

E2 Mechanism

32

E2 Mechanism

33

Cope Elimination

Amine oxides undergo elimination to form the least substituted alkene under milder conditions than the Hofmann reaction.

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DIFFERENCES BETWEEN DIFFERENCES BETWEEN E1 AND E2E1 AND E2

35

E1 formation of carbocation

intermediaterate :tertiary > secondary > primary > methyl

But this same order holds for E2 also.

Structure of substrateStructure of substrate

R-C-XR

RR-C-X

R

HR-C-X

H

H

primary secondary tertiary

tertiary has moreβ

-hydrogens C C

C

C

HH

H

H H

HH H

B r

HEtO-

more opportunitesfor reaction

36

E2 mechanism E1 mechanism

strong base weak base

ALKYL HALIDE + BASEALKYL HALIDE + BASE

solvolysis

must be able to make“good” carbocation

or

anti-coplanar requirement

stereospecific not stereospecific

regioselective regioselective

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E1 or E2?•

Tertiary > Secondary

•

Weak base•

Good ionizing solvent

•

Rate = k[halide]•

Zaitsev

product

•

No required geometry

•

Rearranged products

•

Tertiary > Secondary•

Strong base required

•

Solvent polarity not important

•

Rate =

k[halide][base]•

Zaitsev

product

•

Coplanar leaving groups (usually anti)

•

No rearrangements

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Elimination vs. Substitution

SN

2 and E2

favored over SN

1 and E1 by a strong base/Nu

SN

2 is slowed by steric

hindrance, but E2 is not

Stronger bases

favor E2 over SN

2higher temperatures

favor elimination

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SN

2 E2weaker bases stronger bases

less steric

more sterichindrance hindrance

lower temperature higher temperature

Elimination vs. Substitution

40

Benzylic

halides undergo substitution reactions without competition from elimination.10

benzyl halides react via SN

2

pathway.

CH2Cl+ CH3O- SN2 condition

CH2OCH3

+ Cl-

Elimination vs. Substitution

41

20 and 30

benzyl halides react via SN

1 pathway, without benzylic

rearrangement

CH2ClSN1 condition

CH2+

+ Cl-

CH3OH

+ H+

CH2OCH3

42

ClH2O

Na2CO3HO

Rearranged products are possible from Allyl halides

43

Br

+ Br-X

R CH CHCl R C CHCl + Cl-X

Vinyl halides and aryl halides do not undergo SN

2 reaction because the nucleophile approaches the backside of sp2 carbon and is

repelled by the π

electron cloud of the double bond or the aromatic ring

44

Aryl and vinyl halides do not undergo SN

1 reactions, two reasons:

1. Vinylic

and aryl carbocations

are very unstable

due to positive charge on sp

carbon

atom.2. sp2

carbon atom makes stronger bond

than sp3.

CH

HC

C

H

H H

H

+ 464 kJ

+ 372 kJ

45

PhH2

C-X Ph2

HC-X

Ph3

C-XkSN

1 1

1000108

An exceptionally stable cation

triphenylmethyl

cation used to form ether with a primary alcohol by an SN

1 reaction.Ph

ClPhPh

PhPh

Ph

HO R

slow

-Cl-fast

Py

Ph

OPh

PhR

Ph

OPh

Ph

R

fast

H

46

Cl

SbF6

Steric

hindrance

from backside of the C-Cl

prohibits SN

2

reaction.Carbenium

ion

produced by SN

1 is not planar, therefore is unstable.

Larger bicyclic

system undergo slow SN

1 at bridged head position.

Apocamphyl

chloride 1-bicyclo[3.2.2]nonyl cation

Apocamphyl

chloride is inert to hydroxide ion

47

Substitution or Elimination?

•

Strength of the nucleophile determines order: Strong nucleophile, bimolecular, SN

2 or E2.•

Primary halide usually SN

2.•

Tertiary halide mixture of SN

1, E1 or E2•

High temperature favors elimination.

•

Bulky bases favor elimination.•

Good nucleophiles, but weak bases, favor substitution.