Elimination Reactions

CHM-624
Elimination Reactions
 1,1-elimination or a-elimination is an elimination reaction
in which an organic compound loses two ligands from the
same atom.

 1,2-elimination or b-elimination is an elimination

reaction in which an organic compound loses two ligands
from adjacent atom.
Elimination Reactions

• Two fragments of a molecule are

lost from adjacent carbon atoms
• Multiple bond created
Dehydrohalogenation
β hydrogen
H a carbon
C C
β carbon
X halide as LG
Br
LG t
BuOK t
β a t o + KBr + BuOH
BuOH, 60 C
H
β hydrogen
⊖ OtBu
Common base/solvent pairs used in
dehydrohalogenations

• Potassium hydroxide in ethanol

(i.e., KOH/EtOH)
• Sodium ethoxide in ethanol (i.e.,
EtONa/EtOH)
• Potassium tert-butoxide in tert-
butanol (e.g., t-BuOK/t-BuOH)
The alkoxide is prepared in an excess of alcohol. Thus,
the unreacted alcohol becomes the solvent for the
alkoxide base.
Synthesis of Alkoxides

Oxidation-reduction (metallic sodium)

Acid-base (sodium hydride, NaH)

Synthesis of t-BuOK
1. The E2 Reaction
Et O Et O
H CH3 H CH3
α  H CH3
Cβ C H C C H C C
H H  H H
H Br H Br +

EtO⊖ removes a Partial bonds in Et OH + Br

b proton; C−H the transition C=C is fully
breaks; new p state: C−H and formed and
bond forms and C−Br bonds the other
Br begins to break, new p products are
depart C−C bond forms EtOH and Br⊖
b-hydrogen, leaving group, and base
must be coplanar

An “anti” co-planar arrangement of b-hydrogen and

LG is most favorable.

(This is similar to the requirement, in the SN2 reaction, that the

nucleophile “push out” a leaving group from the opposite side.)
1A. Zaitsev’s Rule
If there are two different types of b-hydrogen,
you can potentially form two different products.

a
̶̶̶ H
B Ha Hb
2-methyl-2-butene

Br
b
̶̶̶ H
2-methyl-1-butene
 ⊖
 When a small base is used (e.g. EtO
⊖
or HO ) the major product will be the
more highly substituted alkene (the
more stable alkene). Examples:
 Zaitsev’s Rule
● In elimination reactions, the more
highly substituted alkene product
predominates
 Stability of alkenes
Me Me Me Me Me H
C C > C C > C C
Me Me Me H H Me

Me Me Me H
> C C > C C
H H H H
1B. Formation of the Less Substituted
Alkene Using a Bulky Base
 Dehydrohalogenations carried
out using a sterically-bulky
base such as t-BuOK favor the
formation of the less
substituted alkane.

 Opposite of Zaitsev’s Rule

 Sometimes called the

Hoffman Rule
 Example of small vs. bulky base
EtO CH3CH CHCH3 (80%)
+
(small) CH3CH2CH CH2 (20%)

CH3CH2CHCH3
Br t CH3CH CHCH3 (30%)
BuO
+
(bulky) CH3CH2CH CH2 (70%)
⊖
EtO
(small base)
H H H H tBuO⊖

H C C C C H (bulky base)
H H Br H
 Zaitsev Rule vs. Hofmann Rule

● Examples
a b
H H
(1) +

Br a b
(eliminate H ) (eliminate H )
o
NaOEt, EtOH, 70 C 69% 31%
t t o
KO Bu, BuOH, 75 C 28% 72%
1C. How to Favor an E2 Mechanism
 When a synthesis must begin with a
primary alkyl halide, use a bulky
base. (Because the steric bulk of the
base will inhibit substitution).

 Use a secondary or tertiary alkyl

halide if possible. (Because steric
hindrance in the substrate will inhibit
substitution)
 Use a high concentration of a
strong and non-polarizable base,
such as an alkoxide. [Because a weak
and polarizable base would not drive
the reaction toward a bimolecular
reaction, thereby allowing unimolecular
processes (such as SN1 or E1 reactions)
to compete.]
 Sodium ethoxide in ethanol
(EtONa/EtOH) and potassium tert-
butoxide in tert-butyl alcohol
(t-BuOK/t-BuOH) are bases typically
used to promote E2 reactions

 Use elevated temperature because

heat generally favors elimination over
substitution. (Because elimination
reactions are entropically favored over
substitution reactions.)
2. The E1 Reaction

a carbon
β hydrogen
H

slow fast
r.d.s.
 E1 and SN1 are competing pathways
(“Does H2O act like a nucleophile or base?”)
CH3 CH3 CH3
H 2O
CH3 C Cl CH3 C OH + CH2 C
CH3 CH3 CH3
slow (major (SN1)) (minor (E1))
r.d.s
CH3 H2O as H2O as
CH3 C nucleophile base
CH3
3. Elimination and Substitution
Reactions Compete with Each Other
3A. How to Determine Whether
Substitution or Elimination is Favored

(a) H C
(b) +X
SN2 Nu C
H C
Nu
C X
(a) (b) C
+ Nu H + X
E2 C
Primary Substrate
 With a strong base, e.g. EtO⊖
● Favor SN2

OEt
SN2: 90%
NaOEt
Br EtOH +

E2: (10%)
Secondary Substrate
 With a strong base, e.g. EtO⊖
● Favor E2 +

E2: 80%
NaOEt
+
Br EtOH

OEt
SN2: 20%
Tertiary Substrate
 With a strong base, e.g. EtO⊖
● E2 is highly favored

NaOEt
+
EtOH
Br OEt
E2: 91% SN1: 9%
Increasing temperature favors elimination even
more! (Elimination is entropically-favored.)
Base/Nu⊖: Small vs. Bulky
 Unhindered “small” base/Nu⊖ (SN2)
NaOMe +
Br MeOH OMe
SN2: 99% E2: 1%

 Hindered “bulky” base/Nu⊖ (E2)

t
KO Bu +
t
Br t O Bu
BuOH SN2: 15% E2: 85%
Basicity and Polarizability
O
O
O CH3
CH3 C O
+
(weak base)
Br SN2: 100% E2: 0%

OEt
EtO +
(strong base)
SN2: 20% E2: 80%
Tertiary Halides: SN1 vs. E1 & E2

EtO OEt
+
(strong
base) E2: 100% SN1: 0%
Br

EtOH OEt
+
heat
E1 + E2: 20% SN1: 80%
4. The E1cB Reaction
 The E1cB (Elimination, Unimolecular, Conjugate Base)
mechanism is a third mechanistic pathway for
elimination reactions.
 In many ways it is the exact opposite of the E1
mechanism, as the first step is deprotonation to form a
carbanion, followed by elimination in the second step.
 It does occasionally come up in introductory organic
chemistry courses, particularly in the mechanism of the
aldol condensation, aryne formation and elimination
of alkenyl halides to give alkynes.
4A. Comparison of The E1cB Reaction with
E1 & E2

The E1cB mechanism and the E1 mechanism are two extremes, with the E2 Mechanism
Lying In The Middle.
4B. The E1cB Reaction
Mechanism
The beta carbon is deprotonated first (form B–H, break C–H). In
the limiting case, this would give an anionic intermediate, the
“conjugate base” of the substrate.
4B. The E1cB Reaction
Mechanism Cont..

 In the second step, the pair of electrons from the conjugate

base then displaces the leaving group, forming a pi bond.

 The mechanism is more likely to occur when the C–H bond is

relatively acidic, as when the alpha carbon is adjacent to an
electron withdrawing group like a ketone, nitrile (CN), or nitro
group (NO2). These groups stabilize negative charge.
4C. Examples E1cB Reaction
1. Aldol Condensation
4C. Examples E1cB Reaction
2. Formation Of Alkynes From Alkenyl Halides
4C. Examples E1cB Reaction
3. Formation Of Arynes From Phenyl Halides
4D.Examples
Example to solve
 since: Br
Only H is
CH3CH2 H trans-
H
H CH3 coplanar
EtO to Br

CH3CH2 + EtO CH3CH2

Br CH3 CH3
 E2 Elimination where there are two axial β hydrogens.

EtO (a)
a
EtO b H
H
1 CH(CH3)2
H3C 4 H
3
2
H
H Cl
Both Ha and Hb hydrogens (b)
are anti to the chlorine in
this, the more stable
conformation
 Synthesis

NaNH 2
C C H C C Na
liq. NH 3

(SN2) I

NaI + C C
 END OF CHAPTER 