Elimination Reactions The E2...

Elimination ReactionsThe E2 Mechanism

H

X

B:

The E2 Mechanism

Freeenergy

(G)

Reaction progress

Eact

The E2 Mechanism

R1

C C

R3

R2

R4 R3

C C

R1 R2

R4

XH

B:- B H

X:-

B:-R1

C C

R3

R2

R4

XH

δ-δ-

δ+

δ+

δ-

transition state

The E2 Mechanism-Why?

The E2 Mechanism-Regioselectivity

C C CH3

CH3

Br

C

H

H

H

H

H

Base Base

CCH2 CH3

CH3C

H

H

Hofmann product(least substituted , and

least stable alkene)

C C

CH3H3C

H3C HZaitsev product

(most substituted, and most stable alkene)


Attack of base Attack of base

“Thermodynamic” product“Kinetic” product


~30% ~70%


2-bromopentane 1-pentene2-pentene

The E2 Mechanism-Stereoselectivity

Regioselectivity-The tendency of a reaction to preferentially produce one constitutional isomer.

Stereoselectivity-The tendency of a reaction to produce one of two stereoisomers in unequal amounts.

Stereospecificity-Used to describe a reaction in which the configuration of the product is dependent on the configuration of the starting material.

CH3 O-

The E2 MechanismWhat if we change the base from

methoxide to t-butoxide?

methoxide

“A bulky base”

C C CH3

CH3

Br

C

H

H

H

H

H

Base Base“Bulky” base attacks preferentially at least

hindered position

“Bulky” base avoids hindered position

CCH2 CH3

CH3C

H

H

Hofmann product(least substituted)

C C

CH3H3C

H3C H

Zaitsev product(most substituted)


The E2 Mechanism-RegioselectivityEffect of Steric Bulk of Base

The E2 Mechanism-RegioselectivityExamples of “Bulky” Bases

N

N

N

N

1,5-Diazabicyclo[4.3.0]non-5-ene(DBN)

1,8-Diazabicyclo[5.4.0]undec-7-ene(DBU)

The E2 Mechanism-RegioselectivityEffect of Steric Bulk of Base

CH3O-

CH3OHBr H

Br

CH2CH3

DBU

Br H

H2O

1a.

b.

c. KOH, H2O

The E2 MechanismStereoselectivity and Stereospecificity

The E2 Mechanism-Stereospecificity

H

X

B:

B

X

H

dba

c

d

b

c

a

The E2 Mechanism-Stereoselectivity and Stereospecificity

Br

H H

H

Base:

Base:

SHBr

HH

Br

HH

HBr

HH

H

H

H

HH

Br

H HH

Base:

Base:

The E2 Mechanism-Stereoselectivity

Major product

BrH

HH

Br

HH

H

Br

HH

H

Br

H

HH

Base:

Base:

R

H

H

Br

H

H

H

Base:

Base:

HH Major product

The E2 Mechanism-Stereoselectvity

HBr

HH

BrH

HH

H

H

H

H

Note:The two enantiomers yield the same major

product from an elimination reaction.

The E2 Mechanism-Stereoselectvity

S

R


HBr

CH3H

Br

HH

CH3Br

HCH3

HR

S

Br

H H

H3CBr

H3C H

H

Base:

Base:

H

H3C

?

Only product


BrH

CH3H

Br

HH

CH3Br

HCH3

H

R

R

Base:

Br

H

HH3C

Base:

HH3C

Br

H3C

HH

?

Only product


HBr

CH3H

BrH

CH3H

R

S

R

R

H

H3C

HH3C

Note:Each of the two

diasteromers yields only one product.

The E2 MechanismRegioselectivity in Cyclohexanes


How do we explain this reaction??

Only this product forms

BrNa+OCH3-


First clue: The reaction shows bimolecular kinetics.

Second clue: Reactions with labelled compounds.

BrNa+OCH3-D

H

H

BrNa+OCH3-H

D

D

no deuterium in the product !!

only the hydrogen is removed !!


Third clue:

BrNa+OCH3-


BrNa+OCH3-


H

Br

CH3

BrCH3

H

BrNa+ OCH3-

major product minor product

BrNa+ OCH3-

H

BrBr

CH3

CH3

only product notformed

no trans hydrogen

least stable conformer !!


Br

Na+OEt-

heat Only product formed and the reaction is very slow !!

H

Br

CH

CH3

H3C CH3

BrHC

CH3

CH3

CH3

no trans hydrogen

ClHO-

ClHO-

3a.

b.

enantiomers

enantiomers

Is one reaction faster than the other????

H

Cl

H

Cl

H

Cl

H

H

Cl

H

Cl

Cl

3c.

d.

constitutionalisomers

constitutionalisomers

Is one reaction faster than the other????

H

Cl

H

Cl

HO-

Cl

HO-

Cl

HO-

Cl

HO-

Cl

H

Cl

H

Cl

What’s Going On Here??Regioselectivity in Cyclohexanes

Major product for both reactions !!

Br

Br

CH3OHheat

CH3OHheatH

H

Elimination ReactionsThe E1 Mechanism

The E1 Mechanism

The E1 Mechanism

Base:

The E1 Mechanism

The E1 MechanismRegioselectivity

The E1 Mechanism RegioselectivityZaitsev Product Favored

The E1 MechanismIn the Presence of Acid

+

Substitution vs Elimination

SN1 vs E1Ionization to form carbocation (rate limiting)

SN1: Nucleophilic attack by solvent (fast)

E1: Basic attack by solvent (fast)

SN1 and E1 Mechanisms

SN1

Rearranged substitution product

E1

Rearranged elimination product

SN2 vs E2

Classification of Nucleophiles (and Bases)

Halides Sulfur nucleophiles

Cl- HS- H2S

Br- RS- RSH

I-

H:-

DBN

DBU

HO-

MeO-

EtO-

OH2O

MeOH

EtOH

Nucleophile (only)

Base(only)

Strong Nuc/Strong Base

Weak Nuc/Weak Base

1º halide

more nucleophilicmore basic

strong bulky base

SN2 + E2

E2SN2 + E2

2º halide

more nucleophilic

weak nucleophilestrong bulky base

SN2 + E2

SN1 + E1+ SN2 + E2E2

weak base SN1 + E1+ SN2 + E2

3º halideweak nucleophile

weak base

more basic E2SN1 + E1SN1 + E1

more nucleophilic SN1

SN2

E2

aproticsolventprotic

solvent

Substitution vs Elimination

Elimination Reactions The E2...

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