Transcript Chapter 9 Elimination Reactions of Alkyl Halides Competition Between

Organic Chemistry
6th Edition
Chapter 9
Paula Yurkanis Bruice
Elimination Reactions
of Alkyl Halides
Competition Between
Substitution and
Elimination
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In addition to substitution, an alkyl halide can undergo an
elimination reaction
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The E2 Reaction
Hydroxide cannot act as a nucleophile in this reaction
because of the bulky tertiary halide. Rather, hydroxide
acts as a base and abstracts a proton.
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The removal of a proton and a halide ion is called
dehydrohalogenation:
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An E2 reaction is also called a b-elimination or a
1,2-elimination reaction:
The weaker the base, the better it is as a leaving group
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The Regioselectivity of the E2 Reaction
The major product of an E2 reaction is the most stable
alkene:
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Reaction coordinate diagram for the E2 reaction of
2-bromobutane and methoxide ion
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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
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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
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Bulky bases affect the product distribution resulting in
the Hofmann product, the least substituted alkene:
Hofmann product
Zaitsev product
However, it takes a lot of steric hindrance for the less
stable product to be the major product:
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Another exception to Zaitsev’s rule
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Consider the elimination of 2-fluoropentane…
A carbanion-like transition state
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Therefore, the major product of an E2 elimination reaction
is the more stable alkene except if the reactants are
sterically hindered or the leaving group is poor
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The E1 Reaction
A unimolecular reaction:
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The E1 reaction, like the SN1 reaction, involves a
carbocation intermediate:
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How does a weak base like water remove a proton from
an sp3 carbon?
1) The presence of a positive charge greatly reduces the
pKa
2) Hyperconjugation weakens the C-H bond by electron
density
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The major product in an E1 reaction is generally the
more substituted alkene
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Reaction coordinate diagram for the E1 reaction of
2-chloro-2-methylbutane
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Because the first step is the rate-determining step, the rate of an
E1 reaction depends both on the ease with which the carbocation
is formed and how readily the leaving group leaves
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Because the E1 reaction forms a carbocation
intermediate, we need to consider carbocation
rearrangement
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Competition Between E2
and E1 Reactions
An E2 is favored by a high concentration of strong base and an
aprotic polar solvent
An E1 is favored by a weak base and a protic polar solvent
Review Section 8.10
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Stereochemistry of the E2 Reaction
The bonds to the eliminated groups (H and X) must be
in the same plane
The anti elimination is favored over the syn elimination
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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
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Consider the stereoselectivity 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
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Reaction coordinate diagram for the E2 reaction of
2-bromopentane and ethoxide ion
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When only one hydrogen is bonded to the b-carbon, the
major product of an E2 reaction depends on the structure
of the alkene
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Stereochemistry of the E1 Reaction
The major stereoisomer obtained from an E1 reaction is
the alkene in which the bulkiest substituents are on
opposite sides of the double bond
Both syn and anti elimination can occur in an E1 reaction
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Elimination from Cyclic Compounds
In an E2 reaction, groups to be eliminated must be in
axial positions
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The hydrogen that is removed and the leaving group
both have to be in the axial position, therefore…
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E1 Elimination from Cyclic Compounds
No axial orientation required for the E1 reaction.
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Utilization of kinetic isotope effect to study a reaction
mechanism
A carbon deuterium bond (C–D) is stronger than a carbon
hydrogen bond (C–H)
The deuterium kinetic isotope effect is 7.1, indicating that a C–H
(or C–D) bond must be broken in the rate-determining step
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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 a
good 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
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Consider the SN2/E2 conditions
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A bulky alkyl halide or a sterically hindered nucleophile
encourages elimination over substitution
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A strong or a bulky base encourages elimination over
substitution
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High temperature favors elimination over substitution:
Why? Because elimination is entropically favorable.
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Tertiary alkyl halides undergo only elimination under
SN2/E2 conditions:
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Consider SN1/E1 conditions:
The elimination reaction favored at higher temperatures.
Primary alkyl halides do not form carbocations; therefore
they cannot undergo SN1 and E1 reactions.
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Substitution and Elimination Reactions
in Synthesis
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In synthesizing an ether, the less hindered group should
be provided by the alkyl halide
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However, the most hindered alkyl halide
should be used if you want to synthesize an alkene
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The E2 reaction should be used if you want to
synthesize an alkene:
Hydroxide
Water
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Consecutive E2 Elimination Reactions
Requires a strong base NaNH2. Reaction carried out in liquid ammonia.
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Synthesis Example
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Synthesis Example
Racemic
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Synthesis Example
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Synthesis Example
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