chapter 10 alkyl halides undergo substitution and ...home.konkuk.ac.kr/~parkyong/classes/chapter...

2015-06-08

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© 2014 Pearson Education, Inc.

Elimination Reactions of Alkyl Halides

Competition Between Substitution and

Elimination

Paula Yurkanis BruiceUniversity of California,

Santa Barbara

Chapter 10


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.


An E2 Reaction


Mechanism for an E2 Reaction

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The Halogen Comes off the Alpha Carbon;the Hydrogen Comes off the Beta Carbon

dehydrohalogenation


The Weakest Base Is the Best Leaving Group


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.


The More Stable AlkeneHas the More Stable Transition State

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Alkene-Like Transition State


More E2 Reactions


Relative Reactivities of Alkyl Halides in an E2 Reaction


The More Stable Alkene is the Major Product

The conjugated alkene is the more stable alkene (an exception to Zaitsev’s rule).

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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.

Need a Lot of Steric Hindrance

forms the more stable alkene

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Fluoride Ion is a Poor Leaving Group

This is another exception to Zaitsev’s rule.


The Transition State is Carbanion-Like


Relative Stabilities of Carbocations


Relative Stabilities of Carbanions

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How the Leaving Group Affects the Product Distribution


E2 Reaction Is Regioselective


An E1 Reaction


The Mechanism for an E1 Reaction

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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.


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.


The More Stable Alkene is the Major Product


The Weakest Base is the Best Leaving Group

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Benzylic and Allylic Halides Undergo E2 Reactions


Benzylic and Allylic Halides Undergo E1 Reactions


The E1 Reaction of Allylic Halides Can Form Two Products


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)

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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


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.


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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.


The More Stable Product is Easier to Form

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E2 and E1 Reactions are Regioselective


E2 and E1 Reactions are Regioselective


The Major Product of an E2 Reaction (Largest Groups Are on Opposite Sides)


When Only One Hydrogen is Bonded to the β-Carbon, the Major Product of an E2 Reaction Depends on the

Structure of the Alkene

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When Only One Hydrogen is Bonded to theβ-Carbon, the Major Product is

Still the More Stable Alkene


E2 Elimination from Six-Membered Rings

Both groups being eliminated must be in axial positions.


H and Cl Must Both Be Axial


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

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Neomenthyl Chloride is Faster

Elimination occurs through the more stable conformer.


Menthyl Chloride is Slower

Elimination occurs through the less stable conformer.


E1 Elimination from Six-Membered Rings

The H and Cl do not have to be in axial positions because the reaction is not concerted.


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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).


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).


Alkyl Halides in SN2 and E2 Reactions

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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


Substitution versus Elimination


Steric Hindrance Favors Elimination


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

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Bulky Bases are Used to Encourage Elimination


Although They are Neutral Bases, They are Strong Bases


A High Temperature Favors Elimination

Why? Because elimination has a greater ∆S‡.


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© 2014 Pearson Education, Inc.∆G‡= ∆H‡–T∆S‡


Under SN2/E2 ConditionsTertiary Alkyl Halide = Only Elimination


Under SN1/E1 Conditions Tertiary Alkyl Halides Undergo Substitution and Elimination


Tertiary (SN1/E1): Substitution is FavoredTertiary (SN2/E2): Only Elimination

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William Ether Synthesis:an SN2 Reaction


Forming an Alkoxide Ion


Synthesizing Butyl Propyl Ether


The less hindered group should be provided by the alkyl halide.

Synthesizing tert-Butyl Ethyl Ether

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Synthesizing an Alkene

The more hindered group should be provided by the alkyl halide.


Synthesizing an Alkyne


Converting an Alkene to an Alkyne


Designing a Synthesis

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