Chapter 9 B. - Alkyl Halide
Elimination Reactions
Organic Chemistry, 5th ed.
Marc Loudon
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Chapter 9 n
The Chemistry of Alkyl Halides Part B – Elimina9on Reac9ons n
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The E1 Reaction
Stereochemistry of E1 Reactions
The E2 Reaction
Stereochemistry of E2 Reactions
Competition Between E2 and E1 Reactions
Elimination from Cyclic Compounds
Competition Between Substitution and Elimination
Substitution and Elimination Reactions in Synthesis
Eric J. Kantorowski
California Polytechnic State University
San Luis Obispo, CA
Chapter 9
The E1 Reaction
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The E1 Reaction
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“E1” stands for “Elimination unimolecular”
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The E1 reaction is a two-step reaction
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The first step is rate-determining
Relative reactivities of alkyl halides in an E1 reaction
are similar to the relative stabilities of carbocations
3o benzylic > 3o allylic > 2o benzylic > 2o allylic > 3o > 1o benzylic > 1o allylic ≈ 2o > 1o > vinyl
Increasing reactivity and C+ stability!
Chapter 9
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Chapter 9
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The E1 Reaction
The E1 Reaction: Stereochemistry
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E1 reaction involves a carbocation
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Therefore rearrangements must be considered
Chapter 9
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With C+ both syn and anti-elimination can occur, so E1 reaction
forms both E and Z products regardless of whether β-carbon is
bonded to one or two H’s
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Chapter 9
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Stereochemistry of the E2 Reac4on The E2 Reaction – A concerted mechanism
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The E2 reac4on can take place in two stereochemically dis4nct ways. Which do you think is favored? n
Syn-­‐elimina/on: the dihedral angle is 0° n
An%-­‐elimina/on: the dihedral angle is 180° Removal of the
Chapter 9
9.5 The E2 Reac9on 7
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8 Stereochemistry of the E2 Reac4on n  ____________________is preferred: n
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The E2 Reaction: Stereochemistry
Substituents are
In anti-elimination,
9.5 The E2 Reac9on §
If two β H’s are available on carbon bearing eliminated H,
the E2 reaction is _____________________ (more of one
stereoisomer is formed), but not _________________
§
Alkene with bulkiest groups on
9 Chapter 9
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What Causes Regioselectivity in E2 Reactions?
The E2 Reaction: Regioselectivity
2-bromobutane has two structurally different βcarbons from which to abstract a hydrogen
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Regioselectivity: More of one constitutional isomer is
formed than the other.
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Look at the two products. Explain why!
Chapter 9
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Transition state resembles alkene product so any
factors stabilizing alkene will stabilize TS
More
Not much difference in stability between two alkenes,
so both are formed, but more stable alkene is major
product
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The E2 Reaction: Regioselectivity
The E2 Reaction: Regioselectivity
Zaitsev’s rule:
Zaitsev’s rule may not apply when conjugated dienes
might be formed
CH3
CH2 CHCH2CHCHCH3
Zaitsev’s rule does not predict the product when
•
CH2 CHCH CHCHCH3
major product
+
CH3
Cl
The most subtituted alkene is not the most stable
alkene (e.g.
•
CH3
HO
CH2 CHCH2CH
CCH3
Or
•  The base
Chapter 9
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Chapter 9
The E2 Reaction: Regioselectivity
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The E2 Reaction: Stereochemistry
When only one hydrogen is on the β carbon at a chiral center
predominantly anti-elimination leads to high stereospecificity
Zaitsev’s rule does not apply when the base
is bulky
Chapter 9
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(2S,3S)-2-bromo-3-phenylbutane
(E)-2-phenyl-2-butene
(2S,3R)-2-bromo-3-phenylbutane
(Z)-2-phenyl-2-butene
Chapter 9
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Deuterium Isotope Effects in E2 Reactions
Leaving Group Effects n
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The trend observed for the SN2 reac4on is seen again for the E2 reac4on n
Why? The C-D bond is somewhat stronger than the C-H bond
This retards the E2 reaction rate
CD2 CH2 Br
+ C2H5O-
rate constant kH
C2H5OH
rate constant kk
H
D
C2H5OH
Typically kH/kD is in the range of
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Referred to as a ____________________
CH
CH2
+ Br- + C2H5OH
CH
CH2
+ Br- + C2H5OD
Provides confirmation of reaction mechanism
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Let’s Prac4ce Structure and Leaving Group Effects -­‐ Let’s Prac4ce Problem 9.2 What product(s) are expected in the ethoxide-­‐promoted β-­‐
elimina4on reac4on of each of the following compounds: a)
2-­‐bromo-­‐2,3-­‐dimethylbutane b)
1-­‐chloro-­‐1-­‐methylcyclohexane 9.4 The SN2 Reac9on + C2H5O-
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9.5 The E2 Reac9on CH2 CH2 Br
Problem 9.18 In each of the following series, arrange the compounds in
order of increasing reactivity in the E2 reaction with Na+
C2H5O—.
9.4 The SN2 Reac9on 19 Page 5
20 Stereochemistry and Regioselec4vity: Let’s Prac4ce Stereochemistry and Regioselec4vity: Let’s Prac4ce Problem 9.41 Tell which of the following alkyl halides can give only one
alkene, and which can give a mixture of alkenes, in the E2
reaction. Problem 9.20 Predict the products, including their stereochemistry, from
the E2 reactions of the following diastereomers of stilbene
dibromide with sodium ethoxide in ethanol. Assume that
one equivalent of HBr is eliminated in each case. (±)
Meso-
9.4 The SN2 Reac9on 9.4 The SN2 Reac9on 21 Competition Between E2 and E1
Reactions
Competition Between E2 and E1
Reactions
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Summary of the Reactivity of Alkyl Halides in Elimination
Reactions
E2 reaction is favored by the same factors that favor SN2
reactions over SN1
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primary alkyl halide
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secondary alkyl halide
tertiary alkyl halide
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_____________alkyl halide electrophiles
_______________________(e.g. HO– or –NH2) in 1°, 2°, or
3° electrophiles
An _______________________in 1°, 2°, or 3° electrophiles
An E1 reaction is favored by
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Chapter 9
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A ________________ (e.g. a neutral solvent)
A ________________________(e.g. H2O or ROH)
Chapter 9
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E2 Reactions of Substituted Cyclohexanes
E1 Reactions of Cyclic Compounds
When a cyclohexyl chloride undergoes an E1 reaction,
there is no requirement that the two groups to be
eliminated be diaxial
The conformer of menthyl chloride that undergoes elimination (with
the Cl and H in required axial positions) is the less stable
conformer; and does not give the most substituted double bond.
Chapter 9
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Chapter 9
SN2 vs E2 Competition Between SN2 and E2
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Primary alkyl halides: Primary halides generally undergo substitution, although
if the halide or the base is hindered, elimination is
possible, favorable if heated
Secondary halides are more difficult to predict
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The stronger and more hindered the base, the more
elimination product is produced
The higher the temperature, the more elimination product
is produced
Tertiary halides never undergo SN2 reaction - elimination
is the only possibility
Chapter 9
9.5 The E2 Reac9on 27
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28 SN2 vs E2 n  Secondary alkyl halides: 9.5 The E2 Reac9on SN2 vs E2 n
9.5 The E2 Reac9on 29 1.
Key ques4ons for evalua4on: Is the alkyl halide primary, secondary, ter4ary? If primary or secondary, is there 2.
Is a Lewis base present? Is it a 3.
What is the solvent? 9.7 Summary of Subs9tu9on and Elimina9on Reac9ons of Alkyl Halides 30 Summary of Subs4tu4on and Elimina4on Summary of Subs4tu4on and Elimina4on n
Base structure: 9.7 Summary of Subs9tu9on and Elimina9on Reac9ons of Alkyl Halides 31 Page 8
32 Summary of Subs4tu4on and Elimina4on Solvent Effects – Let’s Prac4ce Problem 9.3 What subs4u4on and elmina4on products (if any) might be obtained when each of the following alkyl halides is treated with sodium methoxide in methanol? a)
2-­‐bromobutane b)
Methyl iodide c)
Trans-­‐1-­‐bromo-­‐3-­‐methylcyclohexane d)
(bromomethyl)cyclopentane 9.7 Summary of Subs9tu9on and Elimina9on Reac9ons of Alkyl Halides 9.4 The SN2 Reac9on 33 SN2 vs E2– Let’s Prac4ce Problem 9.23 SN1 vs E1– Let’s Prac4ce Problem 9.25 Arrange the following four alkyl halides in descending order with
respect to the E2 elimination to SN2 substitution product ratio expected
in their reactions with sodium ethoxide in ethyl alcohol. Explain your
answers. Give all the products that might be formed when each of the following
alkyl halides undergoes solvolysis in aqueous ethanol. Of the alkenes
formed, which should be the major one(s)?
a)
2-chloro-,3,3-dimethylbutane (the alkyl halide in Eq. 9.60)
b)
2-bromo-2-methylbutane
34 9.4 The SN2 Reac9on 9.4 The SN2 Reac9on 35 Page 9
36 SN2/E2 vs SN1/E1– Let’s Prac4ce Problem 9.29 SN2/E2 vs SN1/E1– Let’s Prac4ce Problem 9.45 What products are expected, including their
stereochemistry, when (2S,3R)-2-bromo-3-methylpentane
is subjected to each of the following conditions? Explain.
Predict the products expected in each of the following situations, and
show the mechanism of any reaction that takes place using the curvedarrow notation.
(a)
1-bromobutane in methanol containing a large excess of sodium
methoxide
(b)
(a)
methanol containing an excess of sodium methoxide
(b)
hot methanol containing no sodium methoxide
2-bromobutane in tert-butyl alcohol containing a large excess of
potassium tert-butoxide
(c)
2-bromo-1,1-dimethylcyclopentane in ethanol
(d)
bromocyclohexane in methanol, heat
9.4 The SN2 Reac9on 9.4 The SN2 Reac9on 37 38 Designing a Synthesis
Substitution and Elimination
Reactions in Synthesis
How would you carry out the following?
SN1/E1 conditions are rarely useful synthetically
Chapter 9
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Chapter 9
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