Chapter 8
Alkyl Halides
and
Elimination Reactions
1
Alkyl Halides and Elimination Reactions
General Features of Elimination
• Elimination reactions involve the loss of elements from
the starting material to form a new π bond in the product.
2
• Equations [1] and [2]
elimination reactions.
illustrate
examples
of
• In both reactions a base removes the elements of an
acid, HX, from the organic starting material.
3
• Removal of the elements HX is called
dehydrohalogenation.
• Dehydrohalogenation is an example of β elimination.
• The curved arrow formalism shown below illustrates
how four bonds are broken or formed in the
process.
4
• The most common bases used in elimination
reactions
are
negatively
charged
oxygen
compounds,
• E.g.: HO¯ and its alkyl derivatives, RO¯, called
alkoxides.
5
• To draw any product of dehydrohalogenation :
(i) Find the α carbon.
(ii) Identify all β carbons with H atoms.
(iii) Remove the elements of H and X from the α and β
carbons and form a π bond.
6
Alkenes—The Products of Elimination
• Recall that the double bond of an alkene consists of a σ
bond and a π bond.
7
• Alkenes are classified according to the number of
carbon atoms bonded to the carbons of the double bond.
Figure 8.1: Classifying alkenes by the number of R groups bonded to the double bond
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• Because of restricted rotation, two stereoisomers of
2-butene are possible.
• cis-2-butene and trans-2-butene are diastereomers
• they are stereoisomers that are not mirror images of
each other.
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• When the two groups on each end of a carboncarbon double bond are different from each other,
two diastereomers are possible.
10
• In general, trans alkenes are more stable than cis
alkenes
• The groups bonded to the double bond carbons in
trans alkenes are further apart, reducing steric
interactions.
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• The stability of an alkene increases as the number of R
groups bonded to the double bond carbons increases.
• The higher the percent s-character, the more readily an
atom accepts electron density.
• sp2 carbons are more able to accept electron density and
sp3 carbons are more able to donate electron density.
• Increasing the number of electron donating groups on a
carbon atom able to accept electron density makes the
alkene more stable.
12
• trans-2-butene is more stable than cis-2-butene
(disubstituted alkenes), but both are more stable
than 1-butene (a monosubstituted alkene).
13
Mechanisms of Elimination
• There are two mechanisms of elimination—E2 and
E1.
• E2 mechanism—bimolecular elimination
• E1 mechanism—unimolecular elimination
• The E2 and E1 mechanisms differ in the timing of
bond cleavage and bond formation, analogous to
the SN2 and SN1 mechanisms.
• E2 and SN2 reactions have some features in
common, as do E1 and SN1 reactions.
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Mechanisms of Elimination—E2
• The
most
common
mechanism
dehydrohalogenation is the E2 mechanism.
for
• It exhibits second-order kinetics, and both the alkyl
halide and the base appear in the rate equation, i.e.,
rate = k[(CH3)3CBr][ ¯OH]
• The reaction is concerted—all bonds are broken and
formed in a single step.
15
16
Figure 8.3: An energy diagram for an E2 reaction:
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• There are close parallels between E2 and SN2
mechanisms in how the identity of the base: the leaving
group and the solvent affect the rate.
• The rate of the E2 reaction increases as the strength of
the base increases.
• E2 reactions are generally run with strong, negatively
charged bases like ¯OH and ¯OR. Two strong sterically
hindered nitrogen bases called DBN and DBU are also
sometimes used.
18
Figure 8.4: An E2 elimination with DBN used as the base
19
20
• The SN2 and E2 mechanisms differ in how the R group
affects the reaction rate.
21
• The increase in E2 reaction rate with increasing
alkyl substitution can be rationalized in terms of
transition state stability.
• In the transition state, the double bond is partially
formed.
• Thus, increasing the stability of the double bond
with alkyl substituents stabilizes the transition state
(i.e., lowers Ea, which increases the rate of the
reaction.
22
• Increasing the number of R groups on the carbon with
the leaving group forms more highly substituted, more
stable alkenes in E2 reactions.
• Hence, 3° alkyl halides reacts faster than the 1º alkyl
halide.
23
Table 8.2 summarizes the characteristics of the E2 mechanism.
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The Zaitsev (Saytzeff) Rule
• When alkyl halides have two or more different β carbons,
more than one alkene product is formed.
• When this happens, one of the products usually
predominates.
• The major product is the more stable product—the one
with the more substituted double bond.
• This phenomenon is called the Zaitsev rule.
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• The Zaitsev rule: the major product in β elimination has
the more substituted double bond.
• A reaction is regioselective when it yields predominantly
or exclusively one constitutional isomer when more than
one is possible.
• Thus, the E2 reaction is regioselective.
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• When a mixture of stereoisomers is possible from a
dehydrohalogenation, the major product is the more
stable stereoisomer.
• A reaction is stereoselective when it forms
predominantly or exclusively one stereoisomer when
two or more are possible.
• The E2 reaction is stereoselective
because one
stereoisomer is formed preferentially.
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Mechanisms of Elimination—E1
• An E1 reaction exhibits first-order kinetics:
rate = k[RX]
• The E1 reaction
mechanism:
proceeds
via
a
two-step
(i) the bond to the leaving group breaks
(ii) π bond is formed.
• The slow step is unimolecular, involving only the
alkyl halide.
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29
Figure 8.6: Energy diagram for an E1 reaction.
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• The rate of an E1 reaction increases as the number of R
groups on the carbon with the leaving group increases.
• The strength of the base usually determines whether a
reaction follows the E1 or E2 mechanism.
• Strong bases like ¯OH and ¯OR favor E2 reactions,
whereas weaker bases like H2O and ROH favor E1
reactions.
31
• E1 reactions are regioselective, favoring formation
of the more substituted, more stable alkene.
• Zaitsev’s rule applies to E1 reactions also.
32
Table 8.3 summarizes the characteristics of the E1 mechanism.
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SN1 vs E1 Reactions
• SN1 and E1 reactions have exactly the same first step—
formation of a carbocation. They differ in what happens
to the carbocation.
• E1 reactions often occur with a competing SN1 reaction,
E1 reactions of alkyl halides are much less useful than
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E2 reactions.
Stereochemistry of the E2 Reaction
• The transition state of an E2 reaction consists of four atoms
from an alkyl halide—all aligned in a plane. There are two ways
for the C—H and C—X bonds to be coplanar.
• E2 elimination occurs most often in the anti periplanar geometry.
• This arrangement allows the molecule to react in the lower
energy staggered conformation
• Allows the incoming base and leaving group to be further away
from each other.
35
Figure 8.7: Two possible geometries for the E2 reaction.
36
• The stereochemical requirement of an anti periplanar geometry
in an E2 reaction has important consequences for compounds
containing six-membered rings.
• Consider chlorocyclohexane which exists as two chair
conformations. Conformation A is preferred since the bulkier Cl
group is in the equatorial position.
• For E2 elimination, the C-Cl bond must be anti periplanar to the
C—H bond on a β carbon, and this occurs only when the H and
Cl atoms are both in the axial position.
• The requirement for trans diaxial geometry means
elimination must occur from the less stable conformer, B.
that
37
Figure 8.8: The trans diaxial geometry for the E2 elimination in chlorocyclohexane
38
• E2 dehydrohalogenation
methylcyclohexane.
of
cis-
and
trans-1-chloro-2-
• This cis isomer exists as two conformations, A and B, each of
which as one group axial and one group equatorial. E2 reaction
must occur from conformation B, which contains an axial Cl
atom.
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• Because conformation B has two different axial β
hydrogens, labeled Ha and Hb, E2 reaction occurs in two
different directions to afford two alkenes.
• The major product contains the more stable
trisubstituted double bond, as predicted by the Zaitsev
rule.
40
• The trans isomer of 1-chloro-2-methylcyclohexane exists
as two conformers: C, having two equatorial substituents,
and D, having two axial substituents.
• E2 reaction must occur from D, since it contains an axial Cl
atom.
41
• Because conformer D has only one axial β H, the E2
reaction occurs only in one direction to afford a single
product. This is not predicted by the Zaitsev rule.
42
When is the Mechanism E1 or E2??
• The strength of the base is the most important factor in
determining the mechanism for elimination.
• Strong bases favor the E2 mechanism. Weak bases favor
the E1 mechanism.
43
E2 Reactions and Alkyne Synthesis
• A single elimination reaction produces a π bond of an
alkene.
• Two consecutive elimination reactions produce two π
bonds of an alkyne.
44
• Two elimination reactions are needed to remove two
moles of HX from a dihalide substrate.
• Two different starting materials can be used—a
vicinal dihalide or a geminal dihalide.
45
• Stronger bases are needed to synthesize alkynes by
dehydrohalogenation than are needed to synthesize
alkenes.
• The typical base used is ¯NH2 (amide), used as the
sodium salt of NaNH2. KOC(CH3)3 can also be used with
DMSO as solvent.
46
• Reason : The transition state for the second elimination
reaction includes partial cleavage of the C—H
bond.
• However, the carbon atom is sp2 hybridized
• sp2 hybridized C—H bonds are stronger than sp3
hybridized C—H bonds.
• A stronger base is needed to cleave this bond.
47
Figure 8.9: Example of dehydrohalogenation of dihalides to afford alkynes.
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Predicting the Mechanism from the Reactants—
SN1, SN2, E1 or E2.
• Good nucleophiles that are weak bases favor
substitution over elimination
• Certain anions generally give products of substitution
because they are good nucleophiles but weak bases.
• These include I¯, Br¯, HS¯, ¯CN, and CH3COO¯.
49
• Bulky nonnucleophilic bases favor elimination over
substitution
• KOC(CH3)3, DBU, and DBN are too sterically hindered to
attack tetravalent carbon, but are able to remove a small
proton, favoring elimination over substitution.
50
Figure 8.10: Determining whether an alkyl halide reacts by an SN1, SN2, E1, or E2 mechanism.
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Figure 8.10-8.10 continued
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Figure 8.10-8.10 continued
53
1. What is the IUPAC name for the structure below?
2. What is the starting material in the reaction below?
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3. What is the product?
4. What is the product?
55
Provide the structure of the major organic product in the
following reaction.
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Q: When 1-iodo-1-methylcyclohexane is treated with
NaOCH2CH3, the more highly substituted alkene
product predominates. When KOC(CH3)3 is used
instead, the less highly substituted alkene product
predominates. Offer an explanation.
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