Elimination Reactions The E2...

Elimination Reactions The E2 Mechanism

H

X

B:

The E2 Mechanism

X-

B-H

Free energy

(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

C C CH3

CH3

C

H

H

H

H

C C CH3

CH3

C

H

H

H

H

Base Base

2-methyl-1-butene

2-methyl-2-butene

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.

The E2 Mechanism What if we change the base from

methoxide to t-butoxide?

methoxide

“A bulky base”

CH3 O C O

CH3

CH3

CH3

“t-butoxide”

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-Regioselectivity Effect of Steric Bulk of Base

The E2 Mechanism-Regioselectivity Examples 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-Regioselectivity Effect of Steric Bulk of Base

Examples

1a.

b.

+cis isomer

+H H H

HH

1c.

d.

e.

1 2 3

KOH, H2O

K⨁ C(CH3)3O⊖

, (CH3)3COH (solv)

1 2 3

OH

CH2CH3Substitution !!!

heat

H

HH

The E2 Mechanism Stereoselectivity and Stereospecificity

The E2 Mechanism-Stereospecificity

H

X

B:

B

X

H

dba

c

d

b

c

a

The E2 Mechanism-Stereoselectivity and Stereospecificity

R1R1 R1

R1 R1

R2

R2

R2R2

R3 R3

R3R3

R4

R4

R4

R4

R4R3

R2R4R3 R1

R2

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

Base

Base


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.

Base

Base

The E2 Mechanism Regioselectivity in Cyclohexanes

H

Br

CH3

BrCH3

H

BrNa+ OCH3-

major product minor product

H

HH

BrNa+ OCH3-

H

BrBr

CH3

CH3

only product not formed

no trans hydrogen

least stable conformer !!

The E2 Mechanism Regioselectivity in Cyclohexanes

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

H

HH

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 Reactions The E1 Mechanism

The E1 Mechanism

Free energy

(G)

Reaction progress

The E1 Mechanism

δ+ δ-

R1

C C

R3

R2

R4

XH

R1

C C

R3

R2

R4

HEact

δ- δ+B:-

R1

C C

R3

R2

R4

H

transition states

R1

C C

R3

R2

R4 R3

C C

R1 R2

R4

XH

B:-

B HX:-

The E1 Mechanism

Base:

The E1 Mechanism

Reaction progress


CH3 CH2 C

CH3

CH3

Cl

CH3 CH2 C

CH3

CH3

CH3 CH2

C

H3C

CH

H

CH3

C CCH3

CH3

H

CH3 C C

C

C

HH

HH

HHH

H

alkene product

The E1 Mechanism Regioselectivity Zaitsev Product Favored

CH3 CHC C

Br

HH

H

H

H

CH3 CH2 CH CH

H20%

CH CHCH3

CH3

CH CHCH3CH3

80%

CH3 CH2HC CH3

Br

KOH, alcohol

The E1 Mechanism Regioselectivity Zaitsev Product Favored

CH3

CH C

CH3

CH3

BrCH3

KOH, alcohol

CH3C C

C

C

BrCH3

H H H

HH

H

H

CH3 CHC

CH3C

H

H

CH321%

CH3

C CCH3

CH3

CH3

79%

The E1 Mechanism In 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

Classification of Nucleophiles (and Bases)

Halides Sulfur nucleophiles Cl- HS- H2S

Br- RS- RSH

I-

H:-

DBN

DBU

HO-

MeO-

EtO-

O

H2O

MeOH

EtOH

Nucleophile (only)

Base(only)

Strong Nuc/Strong Base

Weak Nuc/Weak Base

SN2 vs E2

Regiochemistry Stereochemistry

SN2Nucleophile attacks the position

where the leaving group is attached

Inversion

SN1Nucleophile attacks the

carbocation ⨁ where the leaving group was, unless.......

Racemization

E2Zaitsev product is favored over

Hoffmann product unless a sterically hindered base is used.

Trans alkenes favored.Anti-periplanar elimination

required.

E1Zaitsev product is always favored

over Hoffmann product.Trans alkenes favored.

Table 8.2- Regiochemistry and Stereochemstry of Substitution and Elimination Reactions

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...

Documents

Transcript of Elimination Reactions The E2...