CHAPTER 5

Alkyl Halides
• Alkyl halides or haloalkanes or
halogenoalkanes are the organic
compounds which contain of the halogens
group with a general formula of CnH2n+1X.

• Aryl halides (Ar-X) is the halogen group that

attach to the aromatic ring.
X
Example: Aliphatic Alkyl Halides

Br
1-bromopentane

Cl F
3-fluoro-6-methyloctane

2-chlorohexane
Example: Alicyclic Alkyl Halides
Br

Br
1,3-dibromocyclopentane
Br I
F
Cl
1-chloro-1-iodocyclobutane
Cl
1-bromo-3-chloro-1-fluorocyclohexane
 Classification of Alkyl Halides
• Alkyl halides are classified as primary, secondary
or tertiary depending on the number of alkyl
groups attached to the carbon atom linked to the
halogen atom.

H R R R

H C X H C X R' C X R' C X

H H H R''
primary primary secondary tertiary
Classify the following alkyl halides.

a) 2-bromo-2-methylbutane
b) 3-chloro-2-methylpentane
c) 1-iodocyclopropane
d) 1-chloro-1-methyl cyclopentane
 The SN2 Reaction
• “S” is stands for substitution, “N” for
nucleophilic and “2” for bimolecular.
• Bimolecular means that two molecules
(nucleophile and alkyl halide) are involved in
the rate-determining step.

Reaction rate = k [alkyl halide] [nucleophile]

Concentration in molarity
The rate constant
 The Evidence for SN2 Reaction

• The Reaction Rate

The rate of the reaction depends on the
concentration of the alkyl halide and on the
concentration of the nucleophile. This
means that both reactants are involved in
the rate-determining step.
CH3Br + OH- CH3OH + Br-
• The rate of reaction for the reaction of
CH3Br with hydroxide ion, OH- depends on
the concentrations of both reagents.

• If the concentration of CH3Br in the reaction

mixture is doubled, the rate of reaction
doubles.
Reaction rate = k [CH3Br ] [OH-]
• If the concentration of OH- in the reaction
mixture is doubled, the rate of reaction also
doubles.

Reaction rate = k [CH3Br] [OH- ]

• Because the rate of the reaction of CH3Br and

OH- is linearly dependent on the concentration
of both reactants; the rate constant, k, is
proportional to alkyl halide and nucleophile.

Reaction rate ∞ k [alkyl halide] [nucleophile]

 Stereochemistry of the SN2 Reaction
• In SN2 reactions, the nucleophile, Nu-, approaches
from the opposite side of the leaving group, Br-.
The leaving group departs and the nucleophile
approaches at the same time. The reaction take
place in a one-step mechanism without the
present of intermediates.
H H
CH3
Nu- CH3 C Br Nu C + Br-
D D
• The Types of Alkyl Halide
When the hydrogens of methyl bromide are
replaced by methyl group, the rate of the
reaction become slower.

Alkyl halides Relative rate

CH3Br (1°)
Most reactive
CH3CH2Br (1°)
CH3CH(CH3)Br (2°)
C(CH3)3Br (3°) Least reactive
 Steric Effects in SN2 Reaction
• Steric effects are caused by groups
occupying volume of space.

Less crowding, easier More crowding, blocks

access to the backside access to the backside
of the haloalkane of the haloalkane

H3C H 3C

C Br C Br
H H3C
H3C
H
• Primary alkyl halide is least crowded with
alkyl group make it easier for Nu- to
approach carbon atom compared to tertiary
alkyl halide.

H3C H
H3C H3C
H C Br H C Br
H3C C Br H3C C Br
H H
H3C H

Increase SN2 reactivity

The Leaving Group (LG)
• The best leaving groups are those that can
stabilize the negative charge in the transition
state. The reason leaving ability depends on
basicity; the weaker the basicity, the better
of its leaving group.

• Example: The iodide ion is the weakest base

of the halide ions, therefore it is the best
leaving group and the fluoride ion the
strongest base, therefore it is the worst LG.
• Strong bases such as OH- and NH2- (azanide
ion) make poor leaving groups.
OH-, NH2-, OR-, F-, Cl-, Br-,I-
Increase LG reactivity

• Example: If alkyl halides with the same alkyl

group were react with the same nucleophile
under the same condition; the relative rates
of reaction will be as followed:
Highest atomic no. = least reactive
Most reactive
RCH2I RCH2Br RCH2Cl RCH2F
The Nucleophile
• Stronger bases are better nucleophile. For
example; OH- (which has a negative charge) is
a stronger base and better nucleophile than
H2O (which is neutral).
Stronger base, Weaker base,
better nucleophile poorer nucleophile
HO- H2O
CH3O- CH3OH
NH2 (azanide ion)
-
NH3 (ammonia)
CH3CH2NH- CH3CH2NH2
• Nucleophilicity increases going down a
column of the periodic table, therefore HS-
(bisulfide), is more nucleophilic than OH-.
• The halide reactivity order is as follows:
F- Cl- Br- l-
Increase nucleophilicity

Going down the periodic table, the valence

electrons in larger shells are farther from the
nucleus, less tightly held and more reactive.
The Solvent
• The rates of SN2 reactions are strongly
affected by the solvent. There are two types
of polar solvents; polar protic and polar
aprotic solvents.

• Protic solvents, those with an -OH and –NH

group are the worst for SN2 reactions, while
polar aprotic solvents, polar but without an –
OH and –NH group, are the best for SN2
reactions.
 Aprotic Solvents
• They do not form hydrogen bonds with the
anionic nucleophile, therefore they cannot
function as hydrogen bond donor.

• The solvents accelerate the rate of  SN2

reactions by solvating the cation thus making
the nucleophile more nucleophilic.
Aprotic solvent Structure Polarity of solvent
O
Dimethyl
sulfoxide (DMSO) S
H3C CH3
O These solvents
Acetone favour SN2

increasing
H3C CH3 reactions.

Dichloromethane CH2Cl2

Diethyl ether (CH3CH2)2O

 Protic Solvents
• They contains hydrogen atom bound to an
oxygen or nitrogen. These solvents favor SN1
reactions.
• Protic solvents such as methanol and ethanol
slow down SN2 reactions by solvation of the
reactant nucleophile. The solvent molecules
are capable of intermolecular hydrogen
bonding because they contain an O-H or N-H
bond.
The partial positive
charge that exists in the
O-H hydrogens solvate
the negative charge of
the nucleophile (Nu:-).
Solvated nucleophiles
are held tightly and are
unable to react with the
electrophilic substrates –
compounds that have
leaving group.
Protic solvent Structure Polarity of solvent

Water H2O

Formic acid HCOOH These solvents

favour SN1

increasing
reactions.
Methanol CH3OH

Ethanol CH3CH2OH

Acetic acid CH3COOH

 Effect of different solvents to the reaction
rate

CH2CH2Br CH2CH2CN

CN-
react faster
H2O relative rate = 150,000

CH2CH2Br CH2CH2CN

CN- react slow

CH3OH relative rate = 4
 The SN1 Reaction
• “S” is stands for substitution, “N” for
nucleophilic and “1” for unimolecular.

• Unimolecular means that only one molecule

is involved in the rate-determining step.

Reaction rate = k [alkyl halide]

The rate constant Concentration in molarity

 The Evidence for SN1 Reaction

• The Rate of Reaction

The rate of the reaction depends only on
the concentration of the alkyl halide. This
means that the rate-determining step of
the reaction involves only the alkyl halide.
 CH3 CH3
H3C C Br + H2O H3C C OH + HBr
CH3 CH3

• If the concentration of the alkyl halide is

doubled, the rate of reaction doubles.
However changing the concentration of the
nucleophile has no effect on the reaction.

• The rate law is proportional to alkyl halide

only. Reaction rate = k [alkyl halide]
• The Types of Alkyl Halide
When the methyl group of the tert-butyl
bromide are replaced by hydrogens, the
rate of the SN1 reaction decreases.
Alkyl halides Relative rate
C(CH3)3Br (3°) Most reactive
CH3CH(CH3)Br (2°)
CH3CH2Br (1°)
CH3Br (1°) Least reactive
*Solvent is water, nucleophile also water
• Stereochemistry of the SN1 Reaction
The leaving group departs before the
nucleophile approaches. The reaction take
place in a two-step mechanism.
CH3 CH3
CH3
CH3 C Br step 1
C + Br-
CH3CH2 CH3CH2

• Carbon-halogen bond breaks and form

carbocation intermediate.
 CH3 CH3 CH3
CH 3
C step 2 CH3 C Nu + Nu C CH3

CH3CH2 CH 3CH2 CH3CH2

• In step 2, nucleophile can attack from either

side of the carbocation to produce two
different products.

• Both products are stereoisomers that are

nonsuperimposable mirror image. They are
enantiomers.
 Factors Affecting SN1 Reactions
• The Leaving Group
Tertiary alkyl halide are most reactive
because the more substituted the
carbocation is, the more stable it is to form.

• The nucleophile has no effect on the rate of

SN1 reaction.
Summary of the Reactivity of Alkyl Halides
in Nucleophilic Substitution Reactions.

Types of Alkyl Halides Types of Reaction

Primary SN2 only
Secondary SN1 and SN2
Tertiary SN1 only
Summary

The different between SN2 and SN1 mechanisms

Characteristics SN2 SN1

Type of alkyl halide Primary Tertiary
Type of solvent Aprotic Protic
No. of reactant two one only
mechanism one-step two-steps
Type of reaction Bimolecular Unimolecular
Summary

Carbocation stability = SN1

Never by SN1

R3CX R2CHX RCH2X CH3X

tertiary secondary primary methyl

Never by SN2

Access to the site of reaction = SN2

 Vinyl Halides and Aryl Halides
• Both compounds do not undergo SN1 or
SN2 mechanism because they have a
halogen atom bonded to the sp2
hybridized carbon.
Predict the final product(s) for the following
reactions. Justify your answers.
Cl
CH3OH
a) ?

Na+ I-
b) Br ?
DMSO

Br CH3S-Na+
c) ?
acetone
 Cl OCH3
a) CH3OH + HCl

• 2-chlorobutane is a 2° alkyl halide. Methanol is

a polar protic solvent and is a weak nucleophile.
Therefore, the reaction is by SN1 mechanism.

Na+ I- + -
b) Br I + Na + Br
DMSO

• This is a 1° alkyl halide. Iodide ion is a good

nucleophile and DMSO is aprotic solvent that favour
SN2 reaction. Therefore, the reaction is by SN2
mechanism.
 Br -
CH3S Na +
SCH3
c) +
+ Na + Br -
acetone

• This is a 2° alkyl halide. Bromide ion is a

good leaving group while methyl sulphide
ion is a good nucleophile. Acetone is a polar
aprotic solvent that favour SN2 reaction.
Therefore, the reaction is occur by SN2
mechanism.
 The E2 Reaction
• “E” stands for elimination and “2” stands
for bimolecular.

• E2 is a one-step reaction without

intermediates, occurs when an alkyl halide
is treated with a strong base such as
hydroxide ion or alkoxide ion (RO-).
 CH3 CH3
H3C C CH3 + HO- H2C C CH3
Br + H2O + Br -

• The rate of E2 depends on the

concentration of both tert-butyl bromide
and hydroxide ion; similar to SN2 reaction.

reaction rate = k [alkyl halide] [base]

The E2 Mechanism:
CH3 H CH3
-OH
CH3 C CH2 CH3 C CH2 + H2O + Br-
Br

• The base removes a proton from the carbon that

is adjacent to the carbon bonded to the halogen.
Br- is eliminated from the reaction.
• OH- is called a nucleophile in substitution
reactions because it attacks a carbon and it is
called a base for elimination reactions because it
removes a proton.
 The Identity of the Alkyl Halide
• The SN2 and E2 mechanism differ in how
the R group affects the reaction rate.

Increasing rate of SN2 reaction

primary secondary tertiary

Increasing rate of E2 reaction

• Increase the R groups, increase the rate of

the E2 reaction.
 The E1 Reaction
• “E” stands for elimination and “1” stands
for unimolecular.

• Only the alkyl halide is involved in the

rate-determining step of the reaction.
Therefore, E1 is a two-step reaction.

Reaction rate = k [alkyl halide]

 The E1 Mechanism
• Opposite of the E2 mechanism, E1 reaction
has two-step mechanism; the bond to the
leaving group breaks first before the π
bond is formed.
• Example:

CH3
H3C
CH3 H2O
C CH3 C CH2 + H3O+ + I-
I H3C
Mechanism of the E1 Reactions
• Step 1: The C-I bond is broken and forms an intermediate
carbocation.
CH3
H3C
CH3 C CH3 slow
C CH3 + I-
I H3C
carbocation

• Step 2: A base like H2O removes a proton from a carbon

adjacent to the carbocation and the C-H bond form the
new π bond.

H H3C
H3C
H 2O C CH2 + H3O+
C CH2
H3C H3C
 Characteristics of E1 Reactions

• The rate of E1 reaction increases as the

number of R groups on the carbon with
the leaving group increases.

primary (1°) secondary (2°) tertiary (3°)

Increasing rate of E1 reaction

Summary
A Comparison of E1 and E2 Mechanism
E2 Mechanism E1 Mechanism
Much more common and Much less useful because a
useful. mixture of SN1 and E1
products usually results.

Favored by strong, Favored by weaker, neutral

negatively charged bases bases like water and alcohol.
like –OH and –OR.

The reaction occurs with The mechanism does not

primary, secondary and occur with primary alkyl halide
tertiary alkyl halides. because they form unstable
primary carbocation.
Summary
Summary of the Reactivity of Alkyl Halides
in Nucleophilic Substitution Reactions.

Types of Alkyl Halides Types of Reaction

Primary E2 only
Secondary E1 and E2
tertiary E1 and E2
 Competition between Substitution and
Elimination

• Decide whether the reaction conditions

favor SN2/E2 or SN1/E1.
• Next, decide whether the reaction will form
the substitution, elimination or both
substitution or elimination products.
• The relative amounts of substitution and
elimination product depend on the types of
the alkyl halide.
 SN2/E2 Condition

• The negatively charged species can act as

a nucleophile and attack the back side of
the α-carbon to form the substitution
product; or it can act as a base and remove
a proton from a β-carbon to form the
elimination product.

• Thus, the two reaction compete with each

other.
• A primary alkyl halide is the most reactive
in SN2 reaction and least reactive in E2
reaction, therefore, in a reaction carried
out under condition that favor SN2/E2
reactions substitution product wins the
competition.
• Relative reactivities of alkyl halides
SN2 1° > 2° > 3°
E2 3° > 2° > 1°
SN1 3° > 2° > 1°
E1 3° > 2° > 1°
• A secondary alkyl halide produce both
substitution and elimination products
under SN2/E2 reactions.

• A tertiary alkyl halide is the least reactive

of the alkyl halides in SN2 reaction and the
most reactive in E2 reaction.
• Elimination is the only product forms by
tertiary alkyl halide under the condition
that favor SN2/E2 reactions.
 SN1/E1 Condition
• The reactions secondary and tertiary alkyl
halides in polar protic solvents give a mixture
of substitution or elimination products.

• SN1/E1 reactions form a carbocation as

intermediate which can either combine with
the nucleophile to form the substitution
product or lose a proton to form the
elimination product.
 CH3 CH3 CH3
H2O
H3C C C C H3C C OH
CH3 CH3 CH3
CH3
E1 SN1
H3C C I
CH3 CH3
CH3
CH3CH2OH C C
H3C C
CH3
CH3 E1
CH3
H3C C OCH2CH3
CH3
SN1
Draw the product(s) of the following reactions and
determine either the reactions undergo SN1, SN2, E1
or E2 mechanism.
CH3
CHCH3 solvolysis
Br ?
1. CH3OH

C(CH3)3
2. CH3COO-
?
Br

Br NaSH/DMSO
3.
?
 Cl
CH3CH2OH
4. ?

Br NaCN
5. ?
O

H3C Br
6. Na+O-CH2CH3
H3C CH3 ?
ethanol

7. NaOCH3
Br ?
methanol
The following reaction is referred.

CH3OH
Br + OH- X

a) Determine the reaction mechanism and explain

your answer.
b) State the reaction rate involve in the above
reaction.
c) Provide the mechanism of the reaction.