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Substitution & Elimination Reactions of Alkyl Halides

1. Alkyl halides can undergo substitution and elimination reactions. Substitution involves replacing the halogen with another group, while elimination removes the halogen and a hydrogen to form a double bond. 2. The mechanism of substitution depends on whether it is SN1 or SN2. SN2 is a single step process where the halogen is replaced in a backside attack. SN1 involves formation of a carbocation intermediate. 3. Factors like sterics influence whether substitution or elimination occurs. Primary alkyl halides favor SN2, tertiary favor SN1, and secondary can do both.

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108 views

Substitution & Elimination Reactions of Alkyl Halides

1. Alkyl halides can undergo substitution and elimination reactions. Substitution involves replacing the halogen with another group, while elimination removes the halogen and a hydrogen to form a double bond. 2. The mechanism of substitution depends on whether it is SN1 or SN2. SN2 is a single step process where the halogen is replaced in a backside attack. SN1 involves formation of a carbocation intermediate. 3. Factors like sterics influence whether substitution or elimination occurs. Primary alkyl halides favor SN2, tertiary favor SN1, and secondary can do both.

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Daniel McDermott
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© © All Rights Reserved
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Download as PPT, PDF, TXT or read online on Scribd
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Chapter 7

Substitution & Elimination


Reactions of
Alkyl Halides

We will start considering alkyl halides with X being Cl, Br, or I

Alkyl halides can undergo subsitition and


elimination
Substitution reactionthe electronegative group is replaced by another group.

Elimination reactionthe electronegative group is eliminated along with a hydrogen.

More precisely called a nucleophilic substitution reaction


because the atom replacing the halogen is a nucleophile.

Leaving Group

Nucleophile

A Substitution Reaction

Relative Rates of an SN2 Reaction

Does not
undergo SN2

Tertiary alkyl halides do not undergo SN2 substitution.

If the halogen is bonded to an chiral sp3 cabron,


the product will have the inverted configuration.

Leaving Group

Nucleophile

Inverted Configuration

Summary of the Experimental Evidence


for the Mechanism of an SN2 Reaction
1. The rate of the reaction is dependent on the concentration
of both the alkyl halide and the nucleophile.
2. The relative rate of the reaction is
methyl > primary > secondary
tertiary alkyl halides do not undergo SN2 reactions.

3. If the starting alkyl halide is chiral at the halogen, the


configuration of the product will be inverted.

The Mechanism
back-side attack

Inversion!

Why Bimolecular?

Why Do Methyl Halides React the Fastest


and Tertiary Halides are Unreactive?

steric hindrance

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

Steric Hindrance Decreases Nucleophilicity

Even though the tert-butoxide ion is a


stronger base, it is a poorer nucleophile
because

nucleophilic

attack

is

more

sterically hindered than proton removal.

SN2 Reactions Can Be Used to Make


a Variety of Compounds

The reactions are irreversible because a strong base displaces a weak base.

Tertiary Alkyl Halides & SN1

A tertiary alkyl halide will not undergo SN2 but


will react by an alternate mechanism called SN1

The Product is a Pair of Enantiomers


No inversion (unlike SN2)
Racemization (loss of control over stereochemistry) in SN1

If a halogen is bonded to a chiral center,


the product will be a pair of enantiomers.

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 react the fastest.

3. If the halogen is attached to an asymmetric center


the product will be a pair of enantiomers.

The Mechanism
The leaving group departs before the nucleophile approaches.

Rate-Determining Step

Most SN1 reactions are solvolysis


reactions; the nucleophile is the solvent.

The Rate of an SN1 Depends Only on the


Concentration of the Alkyl Halide

Rate-Determining Step

The Slow Step is Formation of the Carbocation

Tertiary alkyl halides react the fastest


they form the most stable carbocations.
Primary alkyl halides do not undergo SN1 reactions
they form the most unstable carbocations.

Why a Pair of Enantiomers?

The Weakest Base is the Best Leaving Group

pKa
HF
3
HCl -7
HBr -9
HI
-11 Most acidic (most stable X)

Benzylic and Allylic Halides


Undergo SN2 Reactionsbut

Benzylic and Allylic Halides


Can Also Undergo SN1 Reactions

The SN1 Reaction of Allylic Halides


Can Form Two Products

Vinylic and Aryl Halides


Cannot Undergo SN2 Reactions

Vinylic and Aryl Halides


Cannot Undergo SN1 Reactions

Summary of Alkyl Halide Reactivity


Substrate

Substitution Mechanism

methyl and 1o

SN2 only

allylic, benzylic, and 2o

Both SN2 and SN1

3o

SN1 only

vinylic and aryl halides

Neither SN2 or SN1

Intermolecular versus Intramolecular


SN2 Reactions

The Intramolecular Reaction is Favored When


a Five- or Six-Membered Ring Can Be Formed

3-Membered and 4-Membered Rings


are Less Stable

Three-membered rings are generally formed faster than 4-membered rings.

Elimination Reactions of Alkyl


Halides
Competition Between Substitution and
Elimination

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 Halogen Comes off the Alpha Carbon;


the Hydrogen Comes off the Beta Carbon

All elimination reactions are elimination. The double


bond always forms between the and carbons

Stereochemistry

180o

Leaving group and hydrogen must have a


dihedral angle of 180o also called antiperiplanar

Anti Elimination is Preferred

Like SN2, an E2 is a one-step reaction.


The base and the substrate must come together to form the transition state thus
giving the kinetic profile

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.

An E2 Reaction is Regioselective

A disubstituted alkene

A monosubstituted alkene

The major product is the most highly substituted alkene.

Recall Alkene Substitution Patterns

More E2 Reactions

-Identify all carbons


-All possible products will have a bond between the and carbons
-Major product will be the most highly substituted alkene

Conjugation is preferred

The conjugated alkene is the more stable alkene.

An E1 Reaction

Recall the Stabilities of Carbocations

doesnt
form

The Mechanism for an E1 Reaction

An E1 Reaction is Regioselective

The major product is the more substituted alkene.

Benzylic and Allylic Halides


Undergo E2 & E1 Reactions

Conjugated Dienes

Benzylic and Allylic Halides


Undergo E2 & E1 Reactions

Both E2 and E1
Compare these elimination reactions

E2 and E1 Reactions are Regioselective


E2

E1

All elimination reactions are eliminations and


the most substituted alkene is preferred
trans is preferred to cis

E2 Elimination from Six-Membered Rings

Both groups being eliminated must be in axial positions.

H and Cl Must Both Be Axial

Neomenthyl Chloride is Faster

Menthyl Chloride is Slower

SN2 and E2 can compete

2o undergo both E2 and SN2

Under SN2/E2 Conditions


Primary Alkyl Halide = Primarily Substitution

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.

Under SN2/E2 Conditions


Tertiary Alkyl Halide = Only Elimination

Under SN1/E1 Conditions Tertiary Alkyl Halides


Undergo Substitution and Elimination

Tertiary (SN1/E1): Substitution is Favored


Tertiary (SN2/E2): Only Elimination

Weak base

Strong base

William Ether Synthesis:


an SN2 Reaction

Forming an Alkoxide Ion

Synthesizing Butyl Propyl Ether

Synthesizing Ethyl Isopropyl Ether

Synthesizing an Alkene

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

Hydration of an alkene/dehydration of
an alcohol

Dilute vs. concentrated acid


Lots of water
Not very much water
Same mechanism run in reverse

Converting an Alkene to an Alkyne


A special case

Designing a Synthesis

Designing a Synthesis

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