Substitution and

Elimination
Reaction of Alkyl Halides

ALKIL HALIDA
1. Manfaat (Pestisida, Bahan Dasar
Sintesis Alkohol, Alkena)
2. Struktur (Metil, Primer, Sekunder,
Tersier, Benzil dan Vinil)
3. Reaksi (SN-2, SN-1, E-2 dan E-1)

PETA REAKSI ALKIL HALIDA

1.
2.
3.
4.

Metil Halida
Alkil halida Primer
Alkil Halida Sekunder
Alkil Halida Tersier

5.
6.

Alil Halida
Benzil Halida

SN-2
SN-2
SN-2, SN-1 dan E-2
SN-2, SN-1 dan E-2
SN-2, SN-1
SN-2, SN-1

7. Vinil Halida
8. Aril Halida
Dalam Pembahasan Tersendiri

Organic compounds
with an electronegative
atom or an electronwithdrawing group
bonded to a sp3 carbon
undergo substitution or
elimination reactions

Su

ion
t
tu
i
t
bs

Eli
m
ina

Halide ions are good

leaving groups.
Substitution reaction on
these compounds are
easy and are used to get
a wide variety of
compounds

tio
n

alkyl fluoride alkyl chloride alkyl bromidealkyl iodid

4

Alkyl Halides in Nature

Synthesized by red algae

red algae

Synthesized by sea hare

a sea hare

Substitution Reaction with

Halides
(1)

bromomethane
If concentration of (1)
is doubled, the rate of
the reaction is
doubled.
If concentration of (2)
is doubled, the rate of
the reaction is
doubled.

(2)

methanol

If concentration of (1)
and (2) is doubled, the
rate of the reaction
quadruples.

Substitution Reaction with

Halides
(1)

(2)

bromomethane

methanol
Rate law:

rate = k [bromoethane][OH-]
this reaction is an example of a SN2 reaction.
S stands for substitution
N stands for nucleophilic
2 stands for bimolecular

Mechanism of SN2
Reactions
Alkyl halide
The rate of reaction depends on
the concentrations of both
reactants.
When the hydrogens of
bromomethane are replaced with
methyl groups the reaction rate
slow down.
The reaction of an alkyl halide in
which the halogen is bonded to
an asymetric center leads to the
formation of only one
stereoisomer

Relative rate
1200

40

Mechanism of SN2
Reactions
Hughes and Ingold proposed the following
mechanism:

Transition state
Increasing the concentration of either of
the reactant makes their collision more
probable.
9

Mechanism of SN2
Reactions
Steric effect

Energy

activation
energy: G2
activation
energy: G1

reaction coordinate

reaction coordinate

Inversion of
configuration
(S)-2-bromobutane

(R)-2-butanol

10

Factor Affecting SN2

Reactions
The leaving group
relative rates of reaction

pKa HX

HO- + RCH2I

-10

RCH2OH + I-

30 000

RCH2OH + Br-

HO- + RCH2Br
-9
The nucleophile

10 000

HO- + RCH2Cl
RCH2OH + Cl-7 halogen substitution
In general, for
the baseRCH
the OH
better
HOthe
+ strongest
RCH2F
+ F
2
the nucleophile.
3.2

200
1
pKa

Nuclephilicity
11

SN2 Reactions With Alkyl

Halides
an alcohol
a thiol
an ether
a thioether
an amine
an alkyne

a nitrile

12

Substitution Reactions With

Halides

1-bromo-1,1-dimethylethane

1,1-dimethylethanol
Rate law:

If concentration of (1)
is doubled, the rate of
the reaction is
doubled.

rate = k [1-bromo-1,1dimethylethane]

If concentration of (2)
is doubled, the rate of
the reaction is not
doubled.

this reaction is an example of a

SN1 reaction.
S stands for substitution
N stands for nucleophilic
1 stands for unimolecular
13

Mechanism of SN1
Reactions
Alkyl halide
The rate of reaction depends on
the concentrations of the alkyl
halide only.
When the methyl groups of 1bromo-1,1-dimethylethane are
replaced with hydrogens the
reaction rate slow down.
The reaction of an alkyl halide in
which the halogen is bonded to
an asymetric center leads to the
formation of two stereoisomers

Relative rate
0*

0*

12

1 200 000

14

* a small rate is actually observed as a result of a S

Mechanism of SN1
Reactions
nucleophile attacks
the carbocation
slow

C-Br bond
breaks
fast

Proton
dissociation
15

Mechanism of SN1
Reactions
Rate determining
step

Carbocation
intermediate

R++ X+

R-OH2
R-OH

16

Mechanism of SN1
Reactions

Inverted
configuration
relative the alkyl
halide

Same
configuration as
the alkyl halide

17

Factor Affecting SN1

reaction
Two factors affect the rate of a SN1 reaction:
The ease with which the leaving group dissociate from
the carbon
The stability of the carbocation
As in the case of SN2,
The more the
the weaker base is the
substituted the
leaving group, the less
carbocation is, the
tightly it is bonded to
more stable it is and
the carbon and the
therefore the easier it is
easier it is to break the
to form.
bond
The reactivity of the
nucleophile has no effect
on the rate of a SN1
reaction

18

Comparison SN1 SN2

SN1

SN2

A two-step mechanism

A one-step mechanism

A unimolecular ratedetermining step

A bimolecular rate-determining
step

Products have both retained

and inverted configuration
relative to the reactant

Product has inverted

configuration relative to the
reactant

Reactivity order:
3o > 2o > 1o > methyl

Reactivity order:
methyl > 1o > 2o > 3o

19

Kestabilan Karbokation
H

H
H

propan-2-ylium

H
H

+H C
2

CH3+

Ethanylium

Methanylium
20

21

Elimination Reactions

1-bromo-1,1-dimethylethane

2-methylpropene

Rate law:
rate = k [1-bromo-1,1-dimethylethane][OH-]
this reaction is an example of a E2 reaction.
E stands for elimination
2 stands for bimolecular
22

The E2 Reaction
A proton is
removed

Br- is
eliminated

The mechanism shows

that an E2 reaction is a
one-step reaction

23

Elimination Reactions

1-bromo-1,1-dimethylethane

2-methylpropene
Rate law:

If concentration of (1)
is doubled, the rate of
the reaction is
doubled.

rate = k [1-bromo-1,1dimethylethane]

If concentration of (2)
is doubled, the rate of
the reaction is not
doubled.

this reaction is an example of a

E1 reaction.
E stands for elimination
1 stands for unimolecular
24

The E1 Reaction
The base
removes a
proton

The alkyl halide

dissociate,
forming a
carbocation
The mechanism shows
that an E1 reaction is a
two-step reaction

25

Products of Elimination
Reaction
30%

2-bromobutane

50%

80%
2-butene
20%
1-butene

The most stable alkene

is the major product of
the reaction for both E1
and E2 reaction
For both E1 and E2 reactions, tertiary
alkyl halides are the most reactive and
primary alkyl halides are the least
reactive

The greater the

number of alkyl
substituent the more
stable is the alkene
26

ELIMINATION REACTIONS:
ALKENES, ALKYNES

27

Elimination Reactions
Dehydrohalogenation (-HX) and
Dehydration (-H2O) are the main types of
elimination reactions.
C

28

Dehydrohalogenation (-HX)
H
C

C
X

strong
base

"H

X"

X = Cl, Br, I

29

The E2 mechanism
This reaction is done in strong base at high
concentration, such as 1 M NaOH in water.

H_

.. __
O:
..

..
O:
H

H
C

C
Br

_
+

Br

concerted mechanism
30

Kinetics
The reaction in strong base at high
concentration is second order
(bimolecular):
Rate law: rate = k[OH-]1[R-Br]1

31

The E1 mechanism
This reaction is done in strong base such as 0.01
M NaOH in water!! Actually, the base solution is
weak!

1)

H
C

H
slow

rate determining
step

Br

2)

H
H

C
+

_
Br

..
O:
fast

H
C

C
+

.. +
O
H
H
+

32

Kinetics
The reaction in weak base or under
neutral conditions will be first order
(unimolecular):
Rate law: rate = k [R-Br]1
The first step (slow step) is rate
determining!
33

The E2 mechanism

Mechanism
Kinetics
Stereochemistry of reactants
Orientation of elimination (Zaitsevs
rule)
Stereochemistry of products
Competing reactions
34

E2 mechanism
This reaction is done in strong base at high
concentration, such as 1 M NaOH in water.

.. __
O:
..

..
O:
H

H
C

C
Br

_
+

Br

concerted mechanism
35

Kinetics of an E2 reaction
The reactions are second order
(bimolecular reactions).
Rate = k [R-Br]1[Base]1
second order reaction (1 + 1 = 2)
High powered math!!

36

Transition State

..
O:
H

C
Br

energy
H

.. __
O:
..

H O

H
C

C
Br

H
C
Br-

Reaction coordinate
37

Stereochemistry of
reactants

E2 reactions must go by an anti

elimination
This means that the hydrogen atom
and halogen atom must be 180o
(coplanar) with respect to each other!!
Draw a Newman projection formula
and place the H and X on opposite
sides.
38

Stereochemistry of E2
Reaction
CH3 C
CH3

CH3

Br

CH3

H
H

KOH

Alcohol
Solvent

CH3 C
CH3
H

H
H

H and Br are anti structure in conformation!!!!!!!!!

39

(S,S)-diastereomer
CH3

Br
CH3

t-butyl

C
H

KOH
ethanol
heat
???

CH3

CH3
C

???

CH3
C

t-butyl

(E)-isomer

CH3

C
t-butyl

(Z)-isomer

40

This one is formed!

CH3

CH3
C

C
T-butyl

(E)-isomer

41

(R,S)-diastereomer
CH3

Br
C

CH3

t-butyl

C
H

KOH
ethanol
heat
???

CH3

CH3
C

???

CH3
C

T-butyl

(E)-isomer

CH3

C
t-butyl

(Z)-isomer
42

This one is formed!

CH3
C

CH3

C
t-butyl

(Z)-isomer

43

Orientation of elimination:
In reactions of removal of hydrogen
regiochemistry/
Zaitsevs
halides from alkyl halides or the removal
of water from alcohols, the hydrogen
Rule
which is lost will come from the more
highly-branched -carbon.
More branched

H H H

H C C C
CH3
H
X

C H

Less branched
A. N. Zaitsev -- 1875

H
44

Product formed from previous

slide
H
H

C
H

H
C

CH3

C
C

H
More substituted alkene is more stable!!!!!!!!

45

Typical bases used in E2

reactions
High concentration of the following >1M
If the concentration isnt given, assume
that it is high concentration!
Na+ -OH
K+ -OH
Na+ -OR
Na+ -NH2

46

Orientation of
elimination:
Explaination of Zaitsevs rule:
regiochemistry/ Zaitsevs
When you remove a hydrogen atom
Rule
from the more branched position,
you are forming a more highly
substituted alkene.

47

Stereochemistry of
products
The H and X must be anti with
respect to each other in an E2
reaction!
You take what you get, especially
with diastereomers! See the
previous slides of the reaction of
diastereomers.

48

Competing reactions
The substitution reaction (SN2)
competes with the elimination
reaction (E2).
Both reactions follow second order
kinetics!

49

The E1 mechanism
Mechanism
Kinetics
Stereochemistry of reactants
Orientation of elimination (Zaitsevs
rule)

Stereochemistry of products
Competing reactions
50

E1 mechanism
This reaction is done in strong base at low
concentration, such as 0.01 M NaOH in water)
1)

H
C

H
slow

water helps
to stabilize
carbocation

Br

H
2)

C
+

..
O:

H
fast

H
C

C
+

_
Br

..+
O
H
+

51

E1 Reactions
These reactions proceed under neutral
conditions where a polar solvent helps
to stabilize the carbocation
intermediate.
This solvent also acts as a weak base
and removes a proton in the fast step.
These types of reactions are referred
to as solvolysis reactions.

52

 tertiary substrates go by E1 in polar

solvents, with little or no base
present!
typical polar solvents are water,
ethanol, methanol and acetic acid
These polar solvents help stabilize
carbocations
E1 reactions also occur in a low
concentration of base (i.e. 0.01M
NaOH).
53

However!!!!
With strong base (i.e. >1M), goes by E2

54

Structure of the Carbocation

Intermediate

CH3
C

CH3

CH3

55

Carbocation stability order

Tertiary (3o) > secondary (2o) > primary
(1o)

It is hard (but not impossible) to get

primary compounds to go by E1. The
reason for this is that primary
carbocations are not stable!
56

Kinetics of an E1 reaction
E1 reactions follow first order
(unimolecular) kinetics:
Rate = k [R-X]1
The solvent helps to stabilize the
carbocation, but it doesnt appear in
the rate law!!

57

Br

C C
H

C
H

C C

energy

intermediate

Br
C C
H

Reaction
coordinate

+ H

58

Stereochemistry of the
reactants
E1 reactions do not require an anti
coplanar orientation of H and X.
Diastereomers give the same
products with E1 reactions, including
cis- and trans products.
Remember, E2 reactions usually give
different products with
diastereomers.
59

Orientation of elimination
E1 reactions faithfully follow
Zaitsevs rule!
This means that the major product
should be the product that is the
most highly substituted.

60

Stereochemistry of products
E1 reactions usually give the
thermodynamically most stable
product as the major product. This
usually means that the largest
groups should be on opposite sides
of the double bond. Usually this
means that the trans product is
obtained.
61

Competing reactions
The substitution reaction (SN1)
competes with the elimination
reaction (E1).
Both reactions follow first order
kinetics!

62

Whenever there are

carbocations

They can undergo elimination (E1)

They can undergo substitution
(SN1)
They can rearrange
and then undergo elimination
or substituion

63

Rearrangements
Alkyl groups and hydrogen can
migrate in rearrangement reactions
to give more stable intermediate
carbocations.
You shouldnt assume that
rearrangements always occur in all
E1 reactions, otherwise paranoia will
set in!!
64

Comparison of E2 / E1
E1 reactions occur under essentially
neutral conditions with polar solvents,
such as water, ethyl alcohol or acetic acid.
E1 reactions can also occur with strong
bases, but only at low concentration,
about 0.01 to 0.1 M or below.
E2 reactions require strong base in high
concentration, about 1 M or above.

65

Comparison of E2 / E1
E1 is a stepwise mechanism (two or more);
Carbocation intermediate!
E2 is a concerted mechanism (one step)
No intermediate!
E1 reactions may give rearranged products
E2 reactions dont give rearrangement
Alcohol dehydration reactions are E1

66

Bulky leaving groups

This give the anti-Zaitsev product (least
Hofmann
Elimination
substituted product is formed)!

_
CH3 CH2 CH2 CH CH3 OH
CH N+ CH
3

CH3

heat

CH3 CH2 CH CH CH3

6%

+
CH3 CH2 CH2 CH CH2

94%
67

Orientation of elimination:
In bimolecular elimination reactions in the
regiochemistry/
Hofmanns
presence of either a bulky leaving group or
a bulky base, the hydrogen that is lost will
Rule
come from the LEAST highly-branched carbon.
More branched

H H H

H C C C
CH3
H
X

Less branched

C H
H
68

Product from previous slide

H
H

C
H

H
C

CH3

H
C

69

Elimination with bulky

bases
Non-bulky bases, such as hydroxide
and ethoxide, give Zaitsev products.
Bulky bases, such as potassium
tert-butoxide, give larger amounts
of the least substituted alkene
(Hoffmann) than with simple bases.

70

Comparing Ordinary and

Bulky Bases
H
CH3 C

CH

CH3

CH3 Br

NaOC2H5
C2H5OH
heat

H
CH3 C

CH3

CH

CH3

Major

CH

CH2

Major

CH3

H
CH

CH3 Br

CH3

KOC(CH3)3
(CH3)3COH
heat

CH3 C
CH3

71

1-butene: watch out for

competing reactions!
H3C

CH2

CH2

CH2

O-CH3

Non-bulky
KOCH3
H3C

CH2

CH2

CH2

SN2

Br

bulky base
KO-t-butyl

E2

H3C

CH2

CH

CH2

72

Highlights

Dehydrohalogenation -- E2 Mechanism
Zaitsevs Rule
Dehydrohalogenation -- E1 Mechanism
Carbocation Rearrangements -- E1
Elimination with Bulky Leaving Groups
and Bulky Bases -- Hofmann Rule -- E2

73

Competition Between
SN2/E2 and SN1/E1
SN1

SN2

E1

E2

rate = k1[alkyl halide] + k2[alkyl halide][nucleo.] + k3[alkyl halide] +

k2[alkyl halide][base]

SN2 and E2 are favoured by a high concentration of a

good nucleophile/strong base
SN1 and E1 are favoured by a poor nucleophile/weak
base, because a poor nucleophile/weak base disfavours
SN2 and E2 reactions

74

Competition Between
Substitution and Elimination
SN2/E2 conditions:

In a SN2 reaction: 1o > 2o > 3o

In a E2 reaction: 3o > 2o > 1o

90%

10%

75%

25%

100%

75

Competition Between
Substitution and Elimination
SN1/E1 conditions:
All alkyl halides that react under SN1/E1
conditions will give both substitution and
elimination products (50%/50%)

76

Summary
Alkyl halides undergo two kinds of nucleophilic subtitutions:
SN1 and SN2, and two kinds of elimination: E1 and E2.
SN2 and E2 are bimolecular one-step reactions
SN1 and E1 are unimolecular two step reactions
SN1 lead to a mixture of stereoisomers
SN2 inverts the configuration od an asymmetric carbon
The major product of a elimination is the most stable alkene
SN2 are E2 are favoured by strong nucleophile/strong base
SN2 reactions are favoured by primary alkyl halides
E2 reactions are favoured by tertiary alkyl halides

77

REAKSI ADISI ALKENA

78

Addition Reaction of
Alkene
1. HX Addition
Electrophilic Addition (Markovnikov Product)
Free Radical Mechanism (Anti-Mark Product)
2. Hydration (+ H2O)
3. Halogenation/ Hydrohalogenation
4. Reduction or Hydrogenation (+ H2 )
5. Oxidation
6. Multi-step Synthesis

Addition of Halogens to
Alkenes
C

+ X2

electrophilic addition to double bond

forms a vicinal dihalide
X2 = Cl2 or Br2
F2; explosive I2 ; endothermic

Example
Br2
CH3CH

CHCH(CH3)2

CH3CHCHCH(CH3)2

Br

Br

(100%)

Stereochemistry of Halogen Addition

anti
anti addition
addition
H
Br2
H

Br

Br

trans-1,2-Dibromocyclopentane
80% yield; only product
Anti Addition ; Two Bromines add to opposite
sides of the ring

Example
H
H

Cl

Cl2

H
Cl

trans-1,2-Dichlorocyclooctane
73% yield; only product

Mechanism is electrophilic
addition
Br2 is not polar, but it is polarizable
two steps
(1)

formation of bromonium ion &

electrophilic attack

(2)
nucleophilic attack on
bromonium
ion by bromide

NET REACTION
CH2=CH2 + Br2 -> Br-CH2-CH2-Br

Step 1a: Formation of

Bromonium Ion
Br

Br

Br

Br

Mutual polarization
of electron distributions
of Br2 and alkene

Electrons flow
from alkene
toward Br2

Step 1b; Electrophilic

Addition to form Bromonium
Part i
Ion
H

H
C

Br

Br

Br
H

+
C

+ Br-

Part ii

Step 1b; Lone Pair on

Bromine Stabalizes
Carbocation and Forms
Cyclic BromoniumBrIon
+
Br
C
H

+
C

C
H

H
+
Br

H
+ Br-

Step 2; Bromide Ion

Must Attack from
Oppositte Side of Cyclic
Bromonium Ion (anti
addition)
+

Br

Br

Br

Br

+
Br

Br

Example
H
Br2
H

Br

Br

trans-1,2-Dibromocyclopentane
80% yield; only product

+ X2

alkenes react with X2 to form vicinal dihalides

alkenes react with X2 in water to give vicinal
halohydrins

+ X2

+ H2O

+ HX

OH

Examples
H2C

CH2

H2O

Br2

BrCH2CH2OH
(70%)

Cl2
H

OH
H2O

Cl

anti addition: only product

Mechanism; 1) Cl2 is polarized and adds across

double bond. 2) Ion formed is stabalized by lone
pair of Cl.

3) Water
attacks
chloronium
ion from side
opposite (anti
addition)
carbonchlorine bond.
This gives
trans isomer

Regioselectivity
CH3

H3C
Br2
C

CH2

CH3

H2O

CH2Br

H3C
OH
(77%)

Markovnikov's rule applied to halohydrin

formation: the halogen adds to the
carbon having the greater number of
hydrogens.

Hydrogenation (Reduction, +H2) of Ethylene

H
C

HH

Metal
Catalyst
H

exothermic H = 136 kJ/mol

catalyzed by finely divided Pt, Pd, Rh, Ni

Two spatial (stereochemical)

aspects of
alkene hydrogenation:
(1) syn addition of both H atoms to double bond
(2) hydrogenation is stereoselective,
corresponding to addition to less crowded face of
double bond
H
CO2CH3

CO2CH3

H2, Pt

CO2CH3

CO2CH3
H

syn-Additon versus
anti-Addition

syn addition

anti addition

syn-Addition; Metal catalyst

breaks H-H bonds.
B

Y
C

A
H

C
X
H

H
H

syn-Addition; Addition of
H2 across double bonds
takes place in two steps.
B
H

A
C

H3C

Example
of
Stereosel
ective
Reaction

CH3

H
H3C

H3C

H2, cat

H3C

CH3

H
H3C
H

Both products
correspond to
syn addition
of H2.

H
H
H3C

CH3

H3C

CH3

H
H3C

H3C

H2, cat

Top
Topface
faceof
ofdouble
double
bond
bondblocked
blockedby
by
this
thismethyl
methylgroup
group
CH3

H
H
H3C
H

But only this

one is formed.
HH22 adds
addsto
to
bottom
bottom face
faceof
of
double
doublebond.
bond.

Example
of
Stereosel
ective
Reaction