2015-06-08
1
© 2014 Pearson Education, Inc.
Elimination Reactions of Alkyl Halides
Competition Between Substitution and
Elimination
Paula Yurkanis BruiceUniversity of California,
Santa Barbara
Chapter 10
© 2014 Pearson Education, Inc.
Alkyl Halides UndergoSubstitution and Elimination Reactions
In an elimination reaction, a halogen is removed from one carbonand a hydrogen is removed from an adjacent carbon.
A double bond is formed between the two carbonsfrom which the atoms were removed.
© 2014 Pearson Education, Inc.
An E2 Reaction
© 2014 Pearson Education, Inc.
Mechanism for an E2 Reaction
2015-06-08
2
© 2014 Pearson Education, Inc.
The Halogen Comes off the Alpha Carbon;the Hydrogen Comes off the Beta Carbon
dehydrohalogenation
© 2014 Pearson Education, Inc.
The Weakest Base Is the Best Leaving Group
© 2014 Pearson Education, Inc.
An E2 Reaction is Regioselective
The most stable alkene is (generally) obtained by removing a hydrogen from the beta carbon that is bonded to the fewest hydrogens.
The major product is the most stable alkene.
© 2014 Pearson Education, Inc.
The More Stable AlkeneHas the More Stable Transition State
2015-06-08
3
© 2014 Pearson Education, Inc.
Alkene-Like Transition State
© 2014 Pearson Education, Inc.
More E2 Reactions
© 2014 Pearson Education, Inc.
Relative Reactivities of Alkyl Halides in an E2 Reaction
© 2014 Pearson Education, Inc.
The More Stable Alkene is the Major Product
The conjugated alkene is the more stable alkene (an exception to Zaitsev’s rule).
2015-06-08
4
© 2014 Pearson Education, Inc.
The More Stable Alkene is Not the Major Product
A sterically hindered alkyl halide and a sterically hindered base forms the less stable alkene (another exception to Zaitsev’s rule).
© 2014 Pearson Education, Inc.
© 2014 Pearson Education, Inc. © 2014 Pearson Education, Inc.
Need a Lot of Steric Hindrance
forms the more stable alkene
2015-06-08
5
© 2014 Pearson Education, Inc.
Fluoride Ion is a Poor Leaving Group
This is another exception to Zaitsev’s rule.
© 2014 Pearson Education, Inc.
The Transition State is Carbanion-Like
© 2014 Pearson Education, Inc.
Relative Stabilities of Carbocations
© 2014 Pearson Education, Inc.
Relative Stabilities of Carbanions
2015-06-08
6
© 2014 Pearson Education, Inc.
How the Leaving Group Affects the Product Distribution
© 2014 Pearson Education, Inc.
E2 Reaction Is Regioselective
© 2014 Pearson Education, Inc.
An E1 Reaction
© 2014 Pearson Education, Inc.
The Mechanism for an E1 Reaction
2015-06-08
7
© 2014 Pearson Education, Inc.
How Does a Weak Base (Like Water) Remove a Proton From an sp3 Carbon?
1. The presence of the positive charge greatly reduces the pKa.2. Hyperconjugation weakens the C—H bond by draining electron density.
© 2014 Pearson Education, Inc.
The most stable alkene is obtained by removing a hydrogen from the beta carbon that is bonded to the fewest hydrogens.
An E1 Reaction is Regioselective
The major product is the more stable alkene.
© 2014 Pearson Education, Inc.
The More Stable Alkene is the Major Product
© 2014 Pearson Education, Inc.
The Weakest Base is the Best Leaving Group
2015-06-08
8
© 2014 Pearson Education, Inc.
Benzylic and Allylic Halides Undergo E2 Reactions
© 2014 Pearson Education, Inc.
Benzylic and Allylic Halides Undergo E1 Reactions
© 2014 Pearson Education, Inc.
The E1 Reaction of Allylic Halides Can Form Two Products
© 2014 Pearson Education, Inc.
The Reactivity of Alkyl Halides in Elimination Reactions
Elimination reactions of alkyl halides
RULE - E2 reactions are favored by the same factors that favor an SN2 reaction
High concentration of a strong base and aprotic polar solvent (DMSO, DMF)
RULE - E1 reactions are favored by the same factors that favor an SN1 reaction
A weak base and a protic polar solvent (ROH, H2O)
2015-06-08
9
© 2014 Pearson Education, Inc.
Carbocation Rearrangements
RULE - E1 reactions generate a carbocation, and the carbon skeleton can rearrange before proton loss if the rearrangement leads to a more stable carbocation © 2014 Pearson Education, Inc.
The Bonds to Be Broken Must Be in the Same Plane
© 2014 Pearson Education, Inc.
Anti Elimination is Preferred
1. Anti requires the molecule to be in a staggered conformation.2. Back-side attack achieves the best overlap of interacting orbitals (see Figure 9.1).3. It avoids repulsion of the electron-rich base with the electron-rich leaving group.
© 2014 Pearson Education, Inc.
2015-06-08
10
© 2014 Pearson Education, Inc. © 2014 Pearson Education, Inc.
© 2014 Pearson Education, Inc.
Anti Elimination
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.
© 2014 Pearson Education, Inc.
The More Stable Product is Easier to Form
2015-06-08
11
© 2014 Pearson Education, Inc.
E2 and E1 Reactions are Regioselective
© 2014 Pearson Education, Inc.
E2 and E1 Reactions are Regioselective
© 2014 Pearson Education, Inc.
The Major Product of an E2 Reaction (Largest Groups Are on Opposite Sides)
© 2014 Pearson Education, Inc.
When Only One Hydrogen is Bonded to the β-Carbon, the Major Product of an E2 Reaction Depends on the
Structure of the Alkene
2015-06-08
12
© 2014 Pearson Education, Inc.
When Only One Hydrogen is Bonded to theβ-Carbon, the Major Product is
Still the More Stable Alkene
© 2014 Pearson Education, Inc.
E2 Elimination from Six-Membered Rings
Both groups being eliminated must be in axial positions.
© 2014 Pearson Education, Inc.
H and Cl Must Both Be Axial
© 2014 Pearson Education, Inc.
The Value of Keq Depends on Whether the ReactionTakes Place Through the More Stable
Conformer or Through the Less Stable Conformer
Keq is large Keq is small
2015-06-08
13
© 2014 Pearson Education, Inc.
Neomenthyl Chloride is Faster
Elimination occurs through the more stable conformer.
© 2014 Pearson Education, Inc.
Menthyl Chloride is Slower
Elimination occurs through the less stable conformer.
© 2014 Pearson Education, Inc.
E1 Elimination from Six-Membered Rings
The H and Cl do not have to be in axial positions because the reaction is not concerted.
© 2014 Pearson Education, Inc.
2015-06-08
14
© 2014 Pearson Education, Inc.
Kinetic Isotope Effects
Deuterium kinetic isotope effect - ratio of the rate constant observed for a compound containing hydrogen versus rate constant for identical compound in which one or more hydrogens has been replaced by deuterium
C-D bond (5.0 kcal/mol) is ~1.2 kcal/mol stronger than C-H bond
RULE - a C-D bond is more difficult to break than the corresponding C-H bond
RULE - a deuterium kinetic isotope effect > 1 indicates that breaking a C-H (or C-D) must occur during the rate-determining step (only way to affect rate).
© 2014 Pearson Education, Inc.
Proof That the E2 Reaction is Concerted
The deuterium kinetic isotope effect = 7.1. Therefore, the C—D bond is broken in the rate-limiting step.
A carbon deuterium bond (C—D) is stronger than a carbon hydrogen bond (C—H).
© 2014 Pearson Education, Inc. © 2014 Pearson Education, Inc.
Alkyl Halides in SN2 and E2 Reactions
2015-06-08
15
© 2014 Pearson Education, Inc.
Substitution versus Elimination
1° alkyl halides - easy, only can undergo SN2/E2
2°, 3° alkyl halides - can undergo all four reactions, but:
SN2/E2 favored by high concentrations of good Nu: or strong base
SN1/E1 favored by low concentrations of poor Nu: or weak base
Don’t forget how solvent can affect your solution
SN2/E2 is favored by aprotic polar solvents
SN1/E1 is favored by protic polar solvents
© 2014 Pearson Education, Inc.
Substitution versus Elimination
© 2014 Pearson Education, Inc.
Steric Hindrance Favors Elimination
© 2014 Pearson Education, Inc.
Under SN2/E2 Conditions Secondary Alkyl Halide = Substitution and Elimination
Substitution is favored by a weak base.Elimination is favored by a strong base.
Depends on the Nature of the Nucleophile
2015-06-08
16
© 2014 Pearson Education, Inc.
Bulky Bases are Used to Encourage Elimination
© 2014 Pearson Education, Inc.
Although They are Neutral Bases, They are Strong Bases
© 2014 Pearson Education, Inc.
A High Temperature Favors Elimination
Why? Because elimination has a greater ∆S‡.
© 2014 Pearson Education, Inc.
2015-06-08
17
© 2014 Pearson Education, Inc.∆G‡= ∆H‡–T∆S‡
© 2014 Pearson Education, Inc.
Under SN2/E2 ConditionsTertiary Alkyl Halide = Only Elimination
© 2014 Pearson Education, Inc.
Under SN1/E1 Conditions Tertiary Alkyl Halides Undergo Substitution and Elimination
© 2014 Pearson Education, Inc.
Tertiary (SN1/E1): Substitution is FavoredTertiary (SN2/E2): Only Elimination
2015-06-08
18
© 2014 Pearson Education, Inc.
William Ether Synthesis:an SN2 Reaction
© 2014 Pearson Education, Inc.
Forming an Alkoxide Ion
© 2014 Pearson Education, Inc.
Synthesizing Butyl Propyl Ether
© 2014 Pearson Education, Inc.
The less hindered group should be provided by the alkyl halide.
Synthesizing tert-Butyl Ethyl Ether
2015-06-08
19
© 2014 Pearson Education, Inc.
Synthesizing an Alkene
The more hindered group should be provided by the alkyl halide.
© 2014 Pearson Education, Inc.
Synthesizing an Alkyne
© 2014 Pearson Education, Inc.
Converting an Alkene to an Alkyne
© 2014 Pearson Education, Inc.
Designing a Synthesis