Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Chapter 11
Elimination Reactions
of Alkyl Halides
Competition Between
Substitution and
Elimination
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall
In addition to substitution, an alkyl halide can undergo an
elimination reaction
The E2 Reaction
The weaker the base, the better it is as a leaving group
The Regioselectivity of the E2 Reaction
The major product of an E2 reaction is the most stable
alkene
The greater the number of substituents, the more stable
is the alkene
Reaction coordinate diagram for the E2 reaction of
2-bromobutane and methoxide ion
The Zaitsev Rule
The more substituted alkene product is obtained when a
proton is removed from the b-carbon that is bonded
to the fewest hydrogens
The most stable alkene is generally (but not always) the
most substituted alkene
Conjugated alkene products are preferred over the
more substituted alkene product
Do not use Zaitsev’s rule to predict the major product
in these cases
Steric hindrance also affects the product distribution
Another exception to Zaitsev’s rule
Consider the elimination of 2-fluoropentane …
A carbanion-like transition state
Relative stabilities of carbanions
R
R C: R
tertiary
carbanion
least
stable
<
R
R C: H
secondary
carbanion
<
R
H C: H
primary
carbanion
<
H
H C: H
methyl
anion
most
stable
The E1 Reaction
Reaction coordinate diagram for the E1 reaction of
2-chloro-2-methylbutane
Because the E1 reaction forms a carbocation
intermediate, we need to consider carbocation
rearrangement
Competition Between E2 and E1
Reactions
Stereochemistry of the E2 Reaction
The bonds to the eliminated groups (H and X) must be
in the same plane
HX
H
X
the more stable conformation
The anti elimination is favored over the syn elimination
Another view of the E2 reaction mechanism
The best overlap of the interacting orbitals is achieved
through back side attack
Anti elimination avoids repulsion of the electron-rich
base
Consider the regioselectivity of the E2 reaction
The alkene with the bulkiest groups on opposite sides of
the double bond will be formed in greater yield, because
it is the more stable alkene
Reaction coordinate diagram for the E2 reaction of
2-bromopentane and ethoxide ion
The particular alkene isomer that is formed depends on
the configuration of the reactant
Stereochemistry of the E1 Reaction
Elimination from Cyclic Compounds
In an E2 reaction, groups to be eliminated must be trans
to one another
H
Br
H
Br
E1 Elimination from Cyclic Compounds
An E1 reaction involves both syn and anti elimination
Utilization of kinetic isotope effect to study a reaction
mechanism
CH2CH2Br
CD2CH2Br
-
+ CH3CH2O
-
+ CH3CH2O
kH
CH CH2
+ Br- + CH3CH2OH
CD CH2
+ Br- + CH3CH2OD
kD
A carbon deuterium bond (C–D) is stronger than a
carbon hydrogen bond (C–H)
The deterium isotope is 7.1, indicating that C–H (or C–D)
bond must be broken in the rate-determining step
Competition Between Substitution and
Elimination
Alkyl halides can undergo SN2, SN1, E2 and E1
1) decide whether the reaction conditions favor SN2/E2 or SN1/E1
•SN2/E2 reactions are favored by a high
concentration of nucleophile/strong base
•SN1/E1 reactions are favored by a poor
nucleophile/weak base
2) decide how much of the product will be the substitution product
and how much of the product will be the elimination product
Consider the SN2/E2 conditions
A bulky base encourages elimination over substitution
A weak base encourages substitution over elimination
Cl
CH3CHCH3 + CH3CH2O-
OCH2CH3
CH3CHCH3
+ CH3CH CH2 + CH3CH2OH
+ Cl-
strong
base
Cl
O
CH3CHCH3 + CH3C O-
weak
base
O
OCCH3
CH3CHCH3 +
Cl-
Consider SN1/E1 conditions
Substitution and Elimination Reactions
in Synthesis
In synthesizing an ether, the less hindered group should
be provided by the alkyl halide
CH3
CH3CH2Br + CH3COCH3
CH3
Br- + CH3COCH2CH3 + CH2 CH2
CH3
CH3
CH3CH2O- + CH3CBr
CH3
CH3
Br- + CH3C CH2
+ CH3CH2OH
However, the most hindered alkyl halide
should be used if you want to synthesize an alkene
Consecutive E2 Elimination Reactions
Intermolecular Versus Intramolecular
Reactions
• A low concentration of reactant favors an intramolecular
reaction
• The intramolecular reaction is also favored when a fiveor six-membered ring is formed
Three- and four-membered rings are less easily formed
Three-membered ring compounds are formed more
easily than four-membered ring compounds
The likelihood of the reacting groups finding each other
decreases sharply when the groups are in compounds
that would form seven-membered and larger rings.
Now we can design a synthesis …
?
CH3
?
CH3
Br
Br