Substitution and Elimination Reactions: Paula Yurkanis Bruice University of California, Santa Barbara

Chapter 9
Substitution and
Elimination
Reactions
Paula Yurkanis Bruice

University of California,
Santa Barbara
© 2017 Pearson Education, Ltd.

The Families of Group II

The Compounds in Group II
Are Electrophiles
All of the compounds in Group II

have an electron-withdrawing atom or group
that is attached to an sp3 carbon.

Because Group II Compounds Are Electrophiles,
They React with Nucleophiles
substitution reaction—the electronegative group is replaced

by another group.
elimination reaction—the electronegative group is eliminated

along with a hydrogen.
Alkyl Halides
the first of the families

in Group II
Alkyl halides have relatively good leaving groups.

A Substitution Reaction
more precisely called a nucleophilic substitution reaction

because the atom replacing the halogen is a nucleophile

What is the Mechanism of the Reaction?
The kinetics of a reaction—the factors that affect the rate of

the reaction—help determine the mechanism.
The Rate Law
The rate law tells us what molecules are involved in

the transition state of the rate-limiting step.
an SN2 reaction
substitution nucleophilic bimolecular
Relative Rates of an SN2 Reaction

Inverted Configuration
If the halogen is bonded to an asymmetric center,

the product will have the inverted configuration.

Summary of the Experimental Evidence
for the Mechanism of an SN2 Reaction
1. Both the alkyl halide and the nucleophile are in

the transition state of the rate-limiting step.
2. The relative rate:

primary alkyl halide > secondary alkyl halide > tertiary alkyl halide
3. The configuration of the product is inverted

compared to the configuration of the reacting
chiral alkyl halide.

The Mechanism
back-side attack

Why Back-Side Attack?

Why Bimolecular?

Why Do Methyl Halides React the Fastest
and Tertiary the Slowest?
steric hindrance

Steric Hindrance Decreases the Rate

Both are Primary Alkyl Halides,
but They React at Different Rates

Although it is Primary, it Reacts Very Slowly

Why the Configuration of the Product
is Inverted

The Weakest Base is the Best Leaving Group

The Rate of an SN2 Reaction
is Affected by the Leaving Group

Bases and Nucleophiles
A base shares its lone pair with a proton.
A nucleophile shares its lone pair with an atom other than a proton.
Base Strength and Nucleophile Strength
A negatively charged atom is a stronger base and a

better nucleophile than the same atom that is neutral.

If atoms are in the same row,

the strongest base is the best nucleophile.

Polarizability
The larger the atom, the more polarizable it is

(can move more freely toward a positive charge).

Polarizability versus Nucleophilicity
Does the greater polarizability of the larger atoms make up for

their decreased basicity that makes them poorer nucleophiles?
No, if they are in an aprotic polar solvent.

I− is still the poorest nucleophile.
Yes, if they are in a protic polar solvent.

I− is now the best nucleophile.

Solvents
nonpolar solvents: hexane, benzene
Negatively charged species cannot dissolve in nonpolar solvents.
protic polar solvents: have a hydrogen attached to an O

(water, alcohols)
aprotic polar solvents: do not have a hydrogen attached to an O

The strongest base is the best nucleophile unless they

differ in size and they are in a protic polar solvent.
Why Do Protic Polar Solvents Make the Strongest
Bases the Poorest Nucleophiles?
F− is the best nucleophile in an aprotic polar solvent.
I− is the best nucleophile in a protic polar solvent.
Strong bases form strong ion–dipole interactions.
The ion–dipole interactions must be broken

before the nucleophile can react.
Solvent Effects on Nucleophilicity
• Most organic reactions are performed in a liquid solvent
capable of dissolving the reactants, at least to some extent.
• Since substitution reactions involve polar starting materials, polar

solvents are used to dissolve them.
• There are two types of polar solvents: protic and aprotic.
• Nucleophilicity can be affected by the nature of the solvent.
29 29
Solvation by Polar Protic Solvents
• Polar protic solvents solvate both cations and anions well.

• If the salt NaBr is used as a source of the nucleophile Br¯ in H2O:
• The Na+ cations are solvated by ion-dipole interactions with H2O
molecules.
• The Br¯ anions are solvated by strong hydrogen bonding
interactions.
30
Nucleophilicity in Polar Protic Solvents
• Smaller, more electronegative anions are solvated more strongly,

effectively shielding them from reaction.
• In polar protic solvents, nucleophilicity increases down a column of
the periodic table as the size of the anion increases.
• This is the opposite of basicity.
31
Polar Aprotic Solvents
• Polar aprotic solvents also exhibit dipole-dipole interactions, but

they have no O-H or N-H bonds.
• They are incapable of hydrogen bonding.
32
Nucleophilicity in Polar Aprotic Solvents
• Polar aprotic solvents solvate cations by ion-dipole interactions.

• Anions are not well solvated because the solvent cannot hydrogen
bond to them.
• These anions are said to be “naked” and therefore, more reactive.
33
Nucleophilicity vs. Basicity in Polar
Aprotic Solvents
• In polar aprotic solvents, nucleophilicity parallels basicity, and
the stronger base is the stronger nucleophile.
• Because basicity decreases as size increases down a
column, nucleophilicity decreases as well.
34
Aprotic Polar Solvents
They can solvate a cation (+)

better than they can solvate an anion (−).
Crown Ethers
• Crown ethers solvate

the cation, so the
nucleophilic strength of
the anion increases.
• Fluoride becomes a
good nucleophile.
Chapter 6 36
Steric Hindrance Decreases Nucleophilicity
tert-Butoxide ion is a stronger base than ethoxide ion,

but it is a poorer nucleophile.
Its large size makes it difficult for it

to approach the back side of the carbon.

SN2 Reactions Can Be Used to Make
a Variety of Compounds
The reactions are irreversible

because a weak base cannot
displace a strong base.

Synthesizing an Amine
K2CO3 makes the solution basic

so that the amine will exist in its basic form.
Energy Diagrams Showing the Effects of
Substrate, Nucleophile, Leaving Group, and
Solvent on SN2 Reaction Rates.

A Substitution Reaction
a tertiary alkyl halide and a poor nucleophile
The reaction is surprisingly fast,

so it must be taking place by a different mechanism.
The Rate Depends Only on the
Concentration of the Alkyl Halide
The Rate Law
Only the alkyl halide is in the transition state of the rate-limiting step.
an SN1 reaction
substitution nucleophilic unimolecular

Solvolysis Reaction
Most SN1 reactions are solvolysis reactions;

the solvent is the nucleophile.
The Mechanism
The leaving group departs before the nucleophile approaches.
The slow step is carbocation formation.

The Reaction Coordinate Diagram

Substitution Reactions of Alkyl Halides
Primary alkyl halides undergo only SN2 reactions.
Secondary alkyl halides undergo only SN2 reactions.
Tertiary alkyl halides undergo only SN1 reactions.

The Product is a Pair of Enantiomers
If the halogen is bonded to an asymmetric center,

the product will be a pair of enantiomers.

Why a Pair of Enantiomers?

Most SN1 Reactions Lead to
Partial Racemization
Generally more inverted product is formed,

because the front side is partially blocked.

Summary of the Experimental Evidence
for the Mechanism of an SN1 Reaction
1. The rate of the reaction depends only on the

concentration of the alkyl halide.
2. Tertiary alkyl halides, but not primary or

secondary alkyl halides, undergo SN1 reactions.
3. If the halogen is attached to an asymmetric

center, the product will be a pair of enantiomers.


Comparing SN2 and SN1 Reactions

Rate Law for the
Reaction of an Alkyl Halide with a Nucleophile
primary alkyl halides and methyl halides only SN2

They cannot form carbocations.
secondary alkyl halides only SN2

Carbocation formation is too slow to make up
for the large concentration of the nucleophile
in a solvolysis reaction.
tertiary alkyl halides only SN1

They cannot undergo back-side attack.
Nature of the Alkyl Halide
• The most important factor is the identity of the alkyl halide.
54
Effect of the Nucleophile
• Strong nucleophiles (which usually bear a negative charge)

present in high concentrations favor SN2 reactions.
• Weak nucleophiles, such as H2O and ROH favor SN1 reactions by
decreasing the rate of any competing SN2 reaction.
• Consider what happens when the 2˚ alkyl halide A, which can
react by either mechanism, is treated with either the strong
nucleophile HO¯ or the weak nucleophile H2O.
55
Predicting SN1 or an SN2–Nucleophile
• The strong nucleophile favors an SN2 mechanism.
• The weak nucleophile favors an SN1 mechanism.
56
Effect of Leaving Groups
• A better leaving group increases the rate of both SN1 and SN2
reactions.
57
Effect of Solvent
• Polar protic solvents like H2O and ROH favor SN1

reactions because the ionic intermediates (both cations
and anions) are stabilized by solvation.
• Polar aprotic solvents favor SN2 reactions because

nucleophiles are not well solvated, and therefore, are
more nucleophilic.
58
Predicting SN1 or an SN2–Summary
59
Alkyl Halides Undergo
Substitution and Elimination Reactions
In an elimination reaction, a halogen is removed from one carbon

and a hydrogen is removed from an adjacent carbon.
A double bond is formed between the two carbons

from which the atoms were removed.
An E2 Reaction
The alkyl halide and the base

are in the transition state of the rate-limiting step.

The Mechanism for an E2 Reaction

The Halogen Comes off the Alpha Carbon;
the Hydrogen Comes off the Beta Carbon
無法顯
示圖片
dehydrohalogenation

An E2 Reaction is Regioselective
The major product is the most stable alkene.
The most stable alkene is generally obtained by removing a hydrogen

from the beta carbon that is bonded to the fewest hydrogens.

The More Stable Alkene
Has the More Stable Transition State
The major product is the more stable alkene.

Alkene-Like Transition State

More E2 Reactions

Limitations of Zaitsev’s Rule
Zaitsev’s rule leads to the more substituted alkene.
If there is conjugation,
the more substituted alkene might not be the more stable alkene.
Limitations of Zaitsev’s Rule
If the alkyl halide and the base are both bulky,

the base will remove the more accessible hydrogen,
which will lead to formation of the less stable product.

The Steric Properties of the Base
Affect the Product Distribution

Alkyl Fluorides Form the Less Stable Alkene
The major product of the E2 reaction of an alkyl fluoride

is the less stable alkene.

The Transition State is Carbanion-Like
Because the leaving group is poor, the transition state is carbanion-like.

Carbocation and Carbanion Stability

The Leaving Group Affects
the Product Distribution

Relative Reactivities of Alkyl Halides
in an E2 Reaction

An E1 Reaction
Only the alkyl halide is in the transition state

of the rate-limiting step.

The Mechanism for an E1 Reaction

How Does a Weak Base
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.
An E1 Reaction is Regioselective
like an E2 reaction
The major product is the more stable alkene.
The more stable alkene is obtained by removing a hydrogen

from the beta carbon that is bonded to the fewest hydrogens.

The More Stable Alkene is the Major Product
The transition state leading to the more stable alkene

is more stable.

Competition between E2 and E1 Reactions
Primary and secondary alkyl halides undergo E2 reactions.
Tertiary alkyl halides undergo both E2 and E1 reactions.
rate = k2[alkyl halide] [base] + k1[alkyl halide]
For tertiary alkyl halides that can undergo both E2 and E1 reactions:
An E2 reaction is favored by a high concentration of a strong base.
An E1 reaction is favored by a low concentration of a weak base.

Anti Elimination is Preferred
Anti requires the molecule to be in a staggered conformation.
Back-side attack achieves the best overlap of interacting orbitals.
Anti avoids repulsion of the electron-rich base with

the electron-rich leaving group.

An E2 Reaction is Stereoselective
The alkene with the bulkiest groups on opposite sides of the double
is formed in greater yield, because it is the more stable alkene.

Anti Elimination

The More Stable Product is Easier to Form

The Major Product of an E2 Reaction
(the 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 Alkyl Halide

When Only One Hydrogen is Bonded to the β-Carbon,
the Major Product of an E1 Reaction is Still
the More Stable Alkene

Summary of the Stereochemistry
of Substitution and Elimination Reactions

E2 Elimination from Six-Membered Rings
Both groups being eliminated must be in axial positions.

Both H and Cl Must Be Axial
Therefore, only the less stable conformer

undergoes an elimination reaction.

Rate Constant for the Elimination Reaction
k′Keq
The value of Keq depends on whether the reaction takes place

through the more stable conformer or through the less stable conformer.
Keq is large Keq is small

The Reaction is Fast
Elimination occurs through the more stable conformer.

The Reaction is Slow
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.

Comparison of E1 and E2 Mechanisms
• The strength of the base is the most important factor in

determining the mechanism for elimination.
97
SN2 and E2 Reactions of Alkyl Halides

Under SN2/E2 Conditions
Primary Alkyl Halide = Primarily Substitution

Steric Hindrance Favors Elimination
The nucleophile is hindered from getting to the back side of the carbon.

Secondary Alkyl Halide = Substitution and Elimination
Substitution is favored by a weak base.

Elimination is favored by a strong base.

Bulky Bases Favor Elimination

Although They Are Neutral Bases,
They Are Strong Bases

A High Temperature Favors Elimination
Why? Because elimination has a greater ∆S‡.
Elimination forms three products.
Substitution forms two products.

Tertiary Alkyl Halide = Only Elimination

Tertiary Alkyl Halides Undergo Substitution and Elimination

The Product a Tertiary Alkyl Halide Forms
Depends on Base Strength
weak base: SN1 and E1 with substitution favored
strong base: only elimination (E2)

Summary of the Products Obtained
from Substitution and Elimination Reactions

When is the Reaction SN1, SN2, E1, or E2?
• Good nucleophiles that are weak bases favor substitution over

elimination.
• These include I¯, Br¯, HS¯, ¯CN, and CH3COO¯.
109
Bulky Bases Favor Elimination
• Bulky nonnucleophilic bases favor elimination over

substitution.
• KOC(CH3)3, DBU, and DBN are too sterically hindered to
attack tetravalent carbon.
• They are, however, able to remove a small proton, favoring
elimination over substitution.
110
Predicting Reaction Mechanisms (SN1, SN2,
E1, or E2)
Tertiary Alkyl Halides
111
Predicting Reaction Mechanisms (SN1,
SN2, E1, or E2)
Primary Alkyl Halides
112
SN2, E1 or E2)
Secondary Alkyl Halides
113
SN2, E1 or E2)
114
Benzyl and Phenyl Groups

Benzylic and Allylic Halides Undergo SN2 Reactions
Unless benzylic and allylic halides are tertiary,

they readily undergo SN2 reactions.

Benzylic and Allylic Halides Undergo SN1 Reactions
Benzylic and allylic halides also undergo SN1 reactions

because they form relatively stable carbocations.

The SN1 Reaction of an Allylic Halide
Can Form Two Products

Benzylic and Allylic Halides Undergo E2 Reactions
The product is relatively stable because it has conjugated double bonds.

Benzylic and Allylic Halides Undergo E1 Reactions
Benzylic and allylic halides also undergo E1 reactions

because they form relatively stable carbocations.

Vinylic and Aryl Halides Cannot Undergo
SN2 Reactions

Vinylic and Aryl Halides Cannot Undergo
SN1 or E1 Reactions
The carbocation is too unstable to be formed.

A Vinylic Halide Can Undergo
an E2 Reaction
A strong base (−NH2) is required.

Solvation
Polar solvents stabilize charges.

If a Reactant is Charged, Increasing
the Polarity of the Solvent Decreases the Rate
The charge on the

reactants is greater
than the charge on the
transition state. As a
result, increasing the
polarity of the solvent
increases the stability
of the reactants more
than the stability of the
transition state, so the
reaction will be slower.
If the Reactants are Neutral (less highly charged),
Increasing the Polarity of the Solvent Increases the Rate
The charge on the

transition state is greater
than the charge on the
reactants. As a results,
increasing the polarity of
the solvent increases the
stability of the transition
state more than the
stability of the reactants,
so the reaction will be
faster.
How the Solvent Affects the Rate of the
SN1 and E1 Reactions of an Alkyl Halide
If the reactants are neutral,

the charge on the reactants is less than the charge on the transition state.
Increasing the polarity of the solvent stabilizes the transition state

more than it stabilizes the reactant—so the reaction is faster.

The Rate of an SN1 Reaction of an Alkyl Halide
Increases as the Polarity of the Solvent Increases

How the Solvent Affects the Rate of
SN2 and E2 Reactions of Alkyl Halides
If a reactant is charged,
the charge on the reactants is more than the charge on the transition state.
Increasing the polarity of the solvent stabilizes the reactants

more than it stabilizes the transition state—so the reaction is slower.
What Solvent Should Be Used?
an SN2 or E2 reaction of an alkyl halide with a

charged nucleophile/base should be carried out
in an aprotic polar solvent.
an SN2 or E2 reaction of an alkyl halide with a

neutral nucleophile/base should be carried out
in a polar solvent.
an SN1 or E1 reaction of an alkyl halide

should be carried out in a polar solvent.
The Williamson Ether Synthesis
making the alkoxide ion

Examples of the Williamson Ether Synthesis

The Williamson Ether Synthesis
No ether is formed.
The less hindered group should be provided by the alkyl halide.

Using Elimination Reactions
to Synthesize Alkenes
To synthesize an alkene, use the most hindered alkyl halide

possible to maximize elimination and minimize substitution.

Strong Base E2
Weak Base E1 + SN1
The strength of the base affects the amount of the alkene formed.

Intermolecular versus Intramolecular
SN2 Reactions

The Intramolecular Reaction is Favored When
a Five- or Six-Membered Ring Can Be Formed

Designing a Synthesis




Substitution and Elimination Reactions: Paula Yurkanis Bruice University of California, Santa Barbara

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Substitution and Elimination Reactions: Paula Yurkanis Bruice University of California, Santa Barbara

Uploaded by

Copyright:

Available Formats

Chapter 9

Paula Yurkanis Bruice

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

All of the compounds in Group II

© 2017 Pearson Education, Ltd.

substitution reaction—the electronegative group is replaced

elimination reaction—the electronegative group is eliminated

the first of the families

Alkyl halides have relatively good leaving groups.

© 2017 Pearson Education, Ltd.

more precisely called a nucleophilic substitution reaction

© 2017 Pearson Education, Ltd.

The kinetics of a reaction—the factors that affect the rate of

The Rate Law

The rate law tells us what molecules are involved in

© 2017 Pearson Education, Ltd.

If the halogen is bonded to an asymmetric center,

© 2017 Pearson Education, Ltd.

1. Both the alkyl halide and the nucleophile are in

2. The relative rate:

3. The configuration of the product is inverted

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

A base shares its lone pair with a proton.

A negatively charged atom is a stronger base and a

© 2017 Pearson Education, Ltd.

If atoms are in the same row,

© 2017 Pearson Education, Ltd.

The larger the atom, the more polarizable it is

© 2017 Pearson Education, Ltd.

Does the greater polarizability of the larger atoms make up for

No, if they are in an aprotic polar solvent.

Yes, if they are in a protic polar solvent.

© 2017 Pearson Education, Ltd.

nonpolar solvents: hexane, benzene

Negatively charged species cannot dissolve in nonpolar solvents.

protic polar solvents: have a hydrogen attached to an O

aprotic polar solvents: do not have a hydrogen attached to an O

© 2017 Pearson Education, Ltd.

The strongest base is the best nucleophile unless they

F− is the best nucleophile in an aprotic polar solvent.

I− is the best nucleophile in a protic polar solvent.

Strong bases form strong ion–dipole interactions.

The ion–dipole interactions must be broken

• Since substitution reactions involve polar starting materials, polar

• There are two types of polar solvents: protic and aprotic.

• Nucleophilicity can be affected by the nature of the solvent.

• Polar protic solvents solvate both cations and anions well.

• Smaller, more electronegative anions are solvated more strongly,

• Polar aprotic solvents also exhibit dipole-dipole interactions, but

• Polar aprotic solvents solvate cations by ion-dipole interactions.

They can solvate a cation (+)

• Crown ethers solvate