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
