REACTIONS OF ALKYL HALIDES

-Alkyl halides are polarized molecules with partial negative

charge on X & positive charge on the C atom which makes
them easily converted to many other functional groups.
-Alkyl halides may undergo rxns as below:

A. Nucleophilic substitution (SN rxn)

- the X atom is substituted by a nucleophile.
-the rxn is limited to alkyl, allyl and benzyl halides which X
atom are bonded to sp3 carbon atom.
-IMPORTANT: Aryl halides and vinyl halides do not
undergo SN rxn due to being bonded to sp2 carbon atom.

B. Elimination (also called dehydrohalogenation)

-the X ion leaves with another atom or ion (often H+).
-the X is “eliminated” from the molecule after abstraction of
a H atom by a strong base. Elimination rxns occur to
produce alkenes.

C. Formation of organometals

A. Nucleophilic Substitution (SN Rxn)

substrate nucleophile product leaving grp

-in this rxn the species which attacks the substrate is called
the nucleophile as this species has lone pair electrons
available to make a new covalent bond with the C of the C-
X grp. Hence, a new Nu-C bond is formed
-The ion removed is called the leaving group.
-There are 3 types of nucleophile:

Weak Moderate Strong

Nucleophile Nucleophile Nucleophile

F Br (CH3CH2)3P

NH3 HS
H-O-H
CH3-S-CH3 I
CH3-O-H
Cl (CH3CH2)3N H
O
CH3CO C N

OH

CH3O and RO

- Halide ions are good leaving grp because they are the
conjugate base for strong acids.
-The hydroxide and alkoxide ions are the conjugate bases
for weak acids. Hence, hydroxide & alkoxide ions are strong
nucleophile.
 Common Leaving Groups

Note:
-Sulfonates, sulfates, and phosphates are good leaving
groups because they can delocalize the negative charge
over the oxygen atoms.
-Neutral molecules are the leaving groups when the
reaction is carried out in acidic media.

-The ease of nucleophilic substation of alkyl halides are as

below:

R-I > R-Br > R-Cl > R-F

Increase reactivity towards Nu substitution

Types of SN rxn

There are 2 types of SN rxn:

a. SN1 rxn (Substitution, Nucleophilic, unimolecular)
- unimolecular means there is only one molecule involved in
the transition state of the rate-determining step.

b. SN2 rxn (Substitution, Nucleophilic, bimolecular)

a. SN1 rxn (Substitution, Nucleophilic, unimolecular)
-It is first order rxn.
-The term unimolecular, means only one molecule involved
in the transition state of the rate-determining step.
-Rate of rxn dependent of concn of alkyl halide.

Rate SN1 = k[RX]

Mechanism of the SN1 reaction:

Rxn of t-butyl bromide with methanol is shown below.

(fast)

(fast)

Notes:
1st step: Carbocation formation. (slow & rate determining
step)

2nd step: -Nucleophilic attack of the Nu- on the carbocation.

-
Final step: Loss of proton.
(If the nucleophile is water or ROH molecule, a proton will
have to be lost in order to obtain a neutral product)
 Energy Diagram of SN1 rxn

-Rxn SN1 result in racemic mixtures (equal mixtures of

inversion of configuration and retention of configuration
products).

-The carbocation is trigonal planar. The nucleophile can

attack the p orbital at the top or at the bottom.
- If the attack occurs from the top, there will be retention of
configuration. [starting material (R) to product (R)]
- If the nucleophile attacks from the bottom there will be
inversion of configuration. [starting material (R) to product
(S)]

Example:
In the SN1 reaction of cis-1-bromo-3-deuteriocyclopentane
with methanol.

- the carbocation formed can be attacked from either face.

-Because the leaving group (bromide) partially blocks the
front side as it leaves, back-side attack (inversion of
configuration) is slightly favored.
Rearrangement in SN1 rxns
-Since rate determining step is formation of carbocation,
SN1 rxn progress at higher rate when stable carbocation is
obtain.
-rearrangement occur by means of Hydride shift or methyl
shift. Results in multiple products.
Examples:
a. HYDRIDE SHIFT

-the above example shows movement of hydride from C3 to

C2 of molecules.

b. METHYL SHIFT
-one of the CH3 groups on the adjacent carbon migrate to
the 1o carbon at the same time as the X atom leaves to
allow for formation of a more stable 3o carbocation.
Example: Rearrangement on neopentyl carbocation

-Rxn of neopentyl bromide with ethanol gives only a

rearranged substitution product which results from a methyl
shift (represented by the symbol ~CH3 the migration of a
methyl group together with its pair of electrons.
-The methyl shift occurs while bromide ion is leaving, so
that only the more stable tertiary carbocation is formed.

a. SN2 rxn (Substitution, Nucleophilic, bimolecular)

-Bimolecular means the rate limiting step involves reaction
of collision of 2 molecules.
-Follow 2nd order rxn.

Rate SN2 = k[RX][Nu-]

NOTE:
INCREASING CONCN OF NUCLEOPHILE AND ALKYL HALIDE
BY 2 FOLD WILL INCREASE RATE OF RXN ALSO BY 2 FOLD.

-SN2 attack happens to 1o alkyl halide BUT SN2 attack DO

NOT OCCUR on a 2o halide and 3o tertiary halide.
(hindered).
-To form a bond, the nucleophile has to get within bonding
distance of the carbon. A sterically hindered alkyl halide
will prevent the nucleophile from getting close enough to
react.
Example of steric effect on SN2 rxn.
Reaction Mechanism of SN2

(pentacoordinated transition state)

-The result of a backside attack of nucleophile onto

molecule is inversion of configuration (Walden inversion).
-Order of reactivity of alkyl halide towards SN2 rxn is:

CH3 > 1o > 2o > neopentyl > 3o

Energy diagram of SN2 rxn:

 Summary of Substitution Rxns

E1 E2
Promoting Factors
Nucleophile Weak Strong
Solvent Good ionizing solvent Wide variety of solvents
Substrate (RX) 3o > 2o CH3X > 1o > 2o
Leaving group Must be good Must be good
Other AgNO3 forces ionization
Characteristics
Kinetics 1st order , kr[RX] 2nd order, kr[RX] [B:-]
Orientation Most substituted alkene Most substituted alkene
Stereochemistry of Retention & inversion of Walden inversion
product configuration
rearrangements Common Impossible
Question:
Predict the whether the rxns below will under S N1 or SN2
mechanism.
a. CH3CH2I + NaCN CH3CH2CN + NaI

b. (CH3)3CBr + CH3OH (CH3)3OCH3 + HBr

Answers:
a. SN2 mechanism
-because the alkyl halide is a 1o and CN- is a strong
nucleophile.

b. SN1 mechanism
-because substrate is 3o alkyl halide and methanol is a
weak nucleophile.
B. ELIMINATION RXN (E rxn)
- also called dehydrohalogenation rxn & β-elimination rxn.
(removal of H on C- β)
-E stands for elimination
-Occur when the X ion leaves with another atom or ion
(often H+).
-This rxn is favoured when a strong base i.e t-butoxide
(CH3)3CO- or hydroxide ion (-OH) at high temperature is
used.
- An elimination involves the loss of two atoms or groups
from the substrate, usually with formation of a pi bond & is
dependent on the reagents & conditions of rxn involved
-Elimination might be a
1. 1st order (E1) or
2. 2nd order (E2)

a. E1 rxn (elimination, unimolecular)

- 1st order rxn cause the rate-limiting rxn involves one
molecule only.
General Eqn:

base
C C C C HX
B a
X
alkene
- results in formation of alkene.
-Rate-limiting is the formation of carbocation similar as in
SN1 rxn.
Rate E1 = k[RX]

-Hence rate of rxn is dependent on concn of alkyl halide

only.
Reaction mechanism:

-Much like the SN1, the E1 rxn involves carbocation

intermediates.
1st step
The ionization of the molecule to form the carbocation,

2nd step
The abstraction of a proton of the neighboring carbon.
Main product of elimination reactions are alkenes.

Energy diagram for E1 rx

The order of reactivity for E1 rxn is as below:

Benzyl > allyl > 3o > 2o > 1o

Rearrangements in E1 mechanism
-Like other carbocation reactions, the E1 may be
accompanied by rearrangement.
-When the reaction involves carbocation intermediates,
there will be a possibility of rearrangements, so a mixture
of products will be obtained.
Example:

(with hydride shift) (no hydride shift)

b. E2 rxn (elimination, bimolecular)
- A one step rxn and follows 2nd order.
- occur with a strong base present (alkoxide/hydroxide ion).
-Rate of rxn is dependent on concn of akyl halide and base.
Rate E2 = k[RX][base]

This rxn is favoured when the carbon-β is NOT HINDERED

by large substituents.
Rxn Mechanism: Reaction of t-butyl bromide with
methoxide ion in methanol.

-Main product are mixture of alkenes.

- Since E2 rxn requires abstraction of a proton C-β, there
are 2 or more possibilities to give mixtures of products.
Example:

In general, the more substituted alkene will be the major

product.
NOTE
Saytzeff Rule : In elimination reactions the most highly substituted alkene usually
predominates.
Summary of Elimination Rxns
SN1 SN2

Promoting Factors
Base Weak Strong needed
Solvent Good ionizing solvent Wide variety of solvents
Substrate (RX) 3o > 2o 3o > 2 o > 1o
Leaving group Must be good Must be good
Others AgNO3 forces ionization

Characteristics
Kinetics 1st order, kr[RX] 2nd order, kr[RX] [B:-]
Orientation Most substituted alkene Most substituted alkene
Stereochemistry of No special geometry Co-planar transition state
product required
rearrangements Common Impossible
Factors affecting Competition between Substitution (SN) and
Elimination (E) Reactions.
1. Class of alkyl halide
2. Type of nucleophile
3. Concentration of nucleophile
4. Solvent
5. Temperature

1. Class of Alkyl Halide

Alkyl halide Preferred Reaction
1o Nu-
RCH2X RCH2Nu
SN2

2o
Nu- R2CHNu
SN2 + E2
ALKENE

R2CHX

Strong base
ALKENE
E2

3o Nu- weak R3CNu

SN1 + E1
ALKENE

R3CX

Strong base
ALKENE
E2
2. Type of Nucleophile
Weak Nucleophile = SN1 (major product) + E1 (minor)
Strong Nucleophile = SN2 (i.e CN- ions)
Strong Base = E2 (i.e -OH/ alkoxide ions)

3. Concentration of Nucleophile
-Rate of rxn of SN2 and E2 are directly proportional to
concentration of base or nucleophile that are used.
-Reduction of concentration of nucleophiles and bases DOES
NOT EFFECT rate of SN1 and E1 rxn.

4. Type of Solvent
-Aprotic & protic solvents can effect nucleophilic
substitution rxns of alkyl halides.
-Polarized aprotic solvents i.e solvents which does not have
OH grp, acetone, DMSO or acetonitrile.
-Polarized protic solvents (H2O, alcohol & carboxylic acid)
increase reactivity towards SN1 rxn because the solvent aids
in solvation or to stabilize the carbocation. Example:

H H
O R O
H H
carbocation solvated
by water molecules
-Protic solvents also helps to reduce nucleophilicity of
nucleophiles by solvating/stabilizing the nucleophiles.
Example: Nucleophilicity of I- is reduced if ethanol is used
as solvent in rxn medium to promote SN1 rxn.
H H
O I O
H2 CH3C δ -
δ
-
CH2CH3
ethanol helps to
stabilize I-
-Solvents which cannot solvate anions promotes SN2 rxn.
Example: Nucleophilicity of I- is increased in when aprotic
solvent of dimethylsulfoxide (DMSO) is used.
Why?
Because DMSO does not have oxygen atom attached to a H
atom that can be used to solvate anion.
O
CH3 SCH3
DMSO

Question
(R)-2-iodobutane reacts with a mixture of acetone:water
(95%:5%) to give (S)-2-butanol but when mixture of
acetone:water of 30%:70% is used, a mixture of (S)-2-
butanol and (R)-2-iodobutanol is formed. Explain this
phenomenon.

Answer
In mixture of 95%:5% of water and acetone, SN2
substitution rxn occur. High concn of acetone makes the
mixture to have aprotic properties, hence, reduce number
of –OH ions which are unable to solvate the
anion/nucleophiles causing them to be reactive and rxn
takes the SN2 pathway.
H
H3C H CH3 CH3
O S N2 -H-
H C I O C HO C
H -I- CH3 CH3
CH2 CH3 H CH2CH3 CH2CH3
(R)-2-iodobutane (S)-2-iodobutanol
When concn of water is increased, mixture has more protic
properties which able to solvate the anions/nucleophiles
causing them to be less reactive therefore impossible for
SN2 rxn to occur. The system only allows SN1 rxn as the
solvent can help stabilize the carbocation.
CH3
HO C CH3
CH2CH3
(S)-2-iodobutanol
H3C CH3
S N1 H2O -H+
C I
H slow C fast
H3C
CH2 CH3 H CH2 CH3
H3C C OH
(R)-2-iodobutane H3CH2C
(R)-2-iodobutanol

5. Temperature
-Increase in temperature, will increase rate for substitution
and elimination rxns.
-However, an increase in rxn temperature will favour more
elimination rxn to occur.

Question 1:
Predict the product for the rxn of 1-chloro-1-
methylcyclopentane with sodium ethoxide in ethanol.

How to solve?
Draw the structure of 1-chloro-1-methylcyclopentane and it
is found it is a 3o halide.
CH3
Cl

An E2 rxn is favoured as sodium ethoxide is a strong base.

Will give 2 type of products as there are two types of
hydrogen-β (from CH3 and CH2).
CH3 CH2 O- 1
H
2
CH2
CH2 CH3 CH2 OH
Cl Cl-
OR 3

CH3 CH2 O- 1

H H
CH3
CH3 CH3 CH2 OH
2
Cl Cl-
3

Question 2:
Draw the structures of all possible products of E2 rxn when
2-bromobutane reacts with concn NaOH.

How to solve?
NaOH is a strong base which can attack H on the 1st and 3rd
C (these are hydrogen-β) in 2-bromobutane.

H H H

H2C C C CH3
1 2 3
Br H
2-bromobutane
Attack of base on H atom on C1 will give 1-butene
HO-
H H H

H2C C C CH3 CH2 =CHCH2CH3

1 2 3
1-butene
Br H
Or attack of base on H atom on C3 will give 2 isomers of 2-
butene.
Hence, this rxn gives 3 alkene products.
H3C H
C C
HO-
H CH3
H H H
trans-2-butene
H2C C C CH3
1 2 3
Br H H3C CH3
C C
H H

NOTE: cis-2-butene
When doing mechanism for elimination rxn, have to
consider the types of H atoms attached on the C-β as
different types of H atoms will give mixtures of alkenes. The
example is as shown previously for elimination rxn for 2-
bromobutane.
C. FORMATION OF ORGANOMETALS
-Most alkyl halides i.e alkyl (RCl, RBr and RI) reacts with
certain metals to form organometals.
-Grignard reagents is the most common organometallic
compounds formed in organic synthesis.
General Eqns:
Dry ether
R-X + Mg R-MgX (X= Cl, Br or I)
(R= aryl, vinyl or allyl halide)

Ar-CH2X + Mg Dry ether Ar-CH2MgX (X=Cl, Br or I)

benzyl halide

Dry ether
Ar-X + Mg Ar-MgX (X=Cl, Br
or I)
aryl halide

-All classes of alkyl halides can react with Mg metal to form

Grignard reagent. Examples:

Dry ether CH3 CHCH3

CH3 CHCH3 Mg
Cl MgCl

isopropyl chloride isopropylmagnesium chloride

Dry ether CH2MgBr

CH2Br Mg

benzyl chloride benzylmagnesium chloride

Dry ether H2C CHMgI

H2C CHI Mg
iodoethane ethenylmagnesium chloride
(vinyl iodide) (vinylmagnesium chloride)
 Visual Test for Alkyl Halides

A. SN1 rxn (AgNO3 in ethanol)

-All benzyl, allyl and 3o alkyl halides give +ve results of a

white precipitate of AgCl.
-EXCEPT for aryl or vinyl halides which will give –ve results.
-2o alkyl will give precitpitate of AgCl after 5 mintes.
-To be exact, AgCl gives a white precipitate.
AgBr gives a pale yellow precipitate.
AgI gives a pale yellow precipitate.

Examples:
ethanol
R-X + AgNO3 AgX + R+

(+ve for benzyl, allyl and 3o alkyl halides)

ethanol +
R-CH=CHCH2X + AgNO3 AgX + R-CH=CHCH2
allyl halide

B. SN2 rxn (NaI in acetone)

-To distinguish classes of alkyl bromides.
-Iodide ion will replace bromide ion & form NaBr precipitate.
-Rate of rxn of nucleophilic substitution of bromide by
iodide ion is as below:
1o > 2o > 3o
Ease of substitution/rxn

-Aryl & vinyl bromides give a -ve result for NaI in acetone
rxn.
acetone
R-Br + NaI R-I + NaBr
 Uses of Alkyl Halides

A. Pesticides
Cl
Cl Cl
H
Cl C Cl

Cl Cl CCl3

Cl DDT
Lindan
Cl Cl
Cl
Cl
Cl Cl
Cl
Cl Chlordan

B. Coatings
-Teflon is an organofluoro polymer used to coat cooking
utensils, mechanical parts to able to withstand against
abrasion and rust.
-Polyvinyl chloride (PVC) and polyvinylidene are polymers
synthesized from organochloride i.e raincoats and toys from
PVC.