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
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)
The E2 Mechanism-Regioselectivity
Attack of base Attack of base
“Thermodynamic” product“Kinetic” product
The E2 Mechanism-Regioselectivity
~30% ~70%
The E2 Mechanism-Regioselectivity
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
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
The E2 Mechanism-Stereospecificity
HBr
CH3H
Br
HH
CH3Br
HCH3
HR
S
Br
H H
H3CBr
H3C H
H
Base:
Base:
H
H3C
?
Only product
The E2 Mechanism-Stereospecificity
BrH
CH3H
Br
HH
CH3Br
HCH3
H
R
R
Base:
Br
H
HH3C
Base:
HH3C
Br
H3C
HH
?
Only product
The E2 Mechanism-Stereospecificity
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
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
The E1 Mechanism-Regioselectivity
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
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