Unit 5: Chapter 6

Alkyl Halides: Nucleophilic

Substitution and Elimination

Organic Chemistry, 5

th

Edition

L. G. Wade, Jr.

Alkyl Halides

2

Classes of Halides

• Alkyl

: Halogen, X, is directly bonded to

sp

3

carbon.

• Vinyl

: X is bonded to sp

2

carbon of alkene.

• Aryl:

X is bonded to sp

2

carbon on

benzene ring. Examples:

C

H

H

H

C

H

H

Br

alkyl halide

C C

H

H

H

Cl

vinyl halide

I

aryl halide

=
>

Alkyl Halides

3

Polarity and Reactivity

• Halogens are more electronegative than C.
• Carbon-halogen

bond is polar

, so carbon

has partial positive charge.

• Carbon can be

attacked

by a nucleophile.

• Halogen can

leave

with the electron pair.

=>

C

H

H

H

Br

+ -

Alkyl Halides

4

Classes of Alkyl Halides

• Methyl halides

: only one C, CH

3

X

• Primary

: C to which X is bonded has

only one C-C bond, CH

3

CH

2

X.

• Secondary

: C to which X is bonded has

two C-C bonds, (CH

3)2

HCX.

.

• Tertiary

: C to which X is bonded has

three C-C bonds , (CH

3)3

CX.

=>

Alkyl Halides

5

Classify These:

CH

3

CH CH

3

Cl

CH

3

CH

2

F

(CH

3

)

3

CBr

CH

3

I

=>

Alkyl Halides

6

Dihalides

• Geminal dihalide

: two halogen atoms

are bonded to the same carbon

• Vicinal dihalide

: two halogen atoms

are bonded to adjacent carbons.

C

H

H

H

C

H

Br

Br

geminal dihalide

C

H

H

Br

C

H

H

Br

vicinal dihalide

=
>

Alkyl Halides

7

IUPAC Nomenclature

• Name as

halo

alkane.

• Choose the

longest carbon chain

, even if

the halogen is not bonded to any of those

C’s.

• Use

lowest possible

numbers for position.

CH

3

CH CH

2

CH

3

Cl

CH

3

(CH

2

)

2

CH(CH

2

)

2

CH

3

CH

2

CH

2

Br

2-chlorobutane

4-(2-bromoethyl)heptane

=
>

Alkyl Halides

8

Systematic

Common

Common

Names

• Name as alkyl

halide

.

• Useful only for

small

alkyl groups.

• Name these:

CH

3

CH CH

2

CH

3

Cl

(CH

3

)

3

CBr

CH

3

CH

CH

3

CH

2

F

=>

secbutyl

chloride

2-chlorobutane

tert-Butyl

bromide

2bromo-2-methylpropane

1-flouro-2-methylpropane

Alkyl Halides

9

“Trivial” Names

• CH

2

X

2

called methylene halide.

• CHX

3

is a haloform.

• CX

4

is carbon tetrahalide.

• Examples:

CH

2

Cl

2

is methylene chloride

CHCl

3

is chloroform

CCl

4

is carbon tetrachloride.

=>

Alkyl Halides

10

Uses of Alkyl Halides

• Solvents

- degreasers and dry cleaning fluid

• Reagents

for synthesis of other compounds

• Anesthetic

: Halothane is CF

3

CHClBr

CHCl

3

used originally (toxic and carcinogenic)

• Freons

, chlorofluorocarbons or CFC’s

Freon 12, CF

2

Cl

2

, now replaced with Freon 22,

CF

2

CHCl, not as harmful to ozone layer.

• Pesticides

- DDT banned in U.S.

=>

Alkyl Halides

11

Dipole Moments

•



=

4.8 x



x d

, where  is the charge

(proportional to EN, electronegativity) and

d is the distance (bond length) in Angstroms.

• Electronegativities

: F > Cl > Br > I

• Bond lengths

: C-F < C-Cl < C-Br < C-I

• Bond dipoles

:

C-Cl > C-F > C-Br > C-I

1.56 D 1.51 D 1.48 D 1.29 D

• Molecular dipoles

depend on shape, too!

=>

Alkyl Halides

12

Boiling Points

• Greater intermolecular forces, higher b.p.

dipole-dipole attractions not significantly

different for different halides

London forces greater for larger atoms

• Greater mass, higher b.p

.

• Spherical shape decreases b.p.

(CH

3

)

3

CBr CH

3

(CH

2

)

3

Br

73C 102C

=>

Alkyl Halides

13

Densities

• Alkyl fluorides and chlorides

less dense

than water.

• Alkyl dichlorides, bromides, and iodides

more dense

than water.

=>

Alkyl Halides

14

Preparation of RX

• Free radical halogenation

produces mixtures, not good lab

synthesis

unless: all H’s are equivalent, or
halogenation is highly selective.

• Free radical allylic halogenation

produces alkyl halide with double bond

on the neighboring carbon.

=>

Alkyl Halides

15

Chlorination of Methane

• Requires

heat or light

for initiation.

• The most effective wavelength is

blue

,

which is absorbed by chlorine gas.

• Lots of product formed from absorption of

only

one photon

of light (

chain reaction

).

=>

C

H

H

H

H + Cl

2

heat or light

C

H

H

H

Cl + HCl

Alkyl Halides

16

Free-Radical Chain

Reaction

• Initiation

generates a reactive

intermediate

.

• Propagation

: the

intermediate reacts

with

a stable molecule to produce another
reactive

intermediate

(and a product

molecule).

• Termination

: side reactions that destroy

the reactive intermediate.
=>

Alkyl Halides

17

Initiation Step

A chlorine molecule splits

homolytically

into chlorine atoms

(free radicals)

=
>

Cl Cl + photon (

h



)

Cl + Cl

Alkyl Halides

18

Propagation Step (1)

The chlorine

atom collides with a

methane molecule and abstracts
(removes) a H, forming another

free

radical

and one of the products (HCl).

C

H

H

H

H

Cl

+

C

C

H

H

H

H

H

H

+ H Cl

=
>

Alkyl Halides

19

Propagation Step (2)

The methyl free radical collides with

another chlorine molecule, producing
the other product (methyl chloride)
and regenerating the chlorine radical.

C

H

H

H

+

Cl Cl

C

H

H

H

Cl

+

Cl

=
>

Alkyl Halides

20

Overall Reaction

C

H

H

H

H

Cl

+

C

H

H

H

+ H Cl

C

H

H

H

+

Cl Cl

C

H

H

H

Cl

+

Cl

C

H

H

H

H + Cl Cl

C

H

H

H

Cl

+ H Cl

=
>

Cl Cl + photon (

h



)

Cl + Cl

Alkyl Halides

21

Termination Steps

• Collision of any two free radicals
• Combination of free radical with

contaminant or collision with wall.

C

H

H

H

Cl

+

C

H

H

H

Cl

Can you suggest others?

=>

Alkyl Halides

22

Halogenation of

Alkanes

• All H’s equivalent. Restrict amount of

halogen to prevent di- or trihalide
formation

• Highly selective: bromination of 3C

=>

+ HBr

H

Br

h



Br

2

+

H

H

90%

+ HBr

CH

3

C

CH

3

CH

3

Br

h



Br

2

+

CH

3

C

CH

3

CH

3

H

Alkyl Halides

23

Allylic Halogenation

• Allylic radical is resonance stabilized.
• Bromination occurs with good yield at

the allylic position (sp

3

C next to C=C).

• Avoid a large excess of

Br

2

by using

N-bromosuccinimide (NBS)

to generate

Br

2

as product HBr is formed.

N

O

O

Br + HBr

N

O

O

H + Br

2

=>

Alkyl Halides

24

Reaction Mechanism

Free radical chain reaction

initiation, propagation,

termination.

H

H

Br

H

+ HBr

Br

Br

H

Br

+ Br

=>

2Br

Br

2

h



Allylic Halogenation

Alkyl Halides

25

Chlorination of Propane

• There are

six 1 H’s

and

two 2’s

. We

expect 3:1

product mix, or 75% 1-

chloropropane and 25% 2-chloropropane.

• Typical product mix:

40%

1-chloropropane

and

60%

2-chloropropane.

• Therefore, not all H’s are equally reactive.

=>

1 C

2 C

CH

3

CH

2

CH

3

+ Cl

2

h



CH

2

Cl

CH

2

CH

3

+ CH

3

CH

Cl

CH

3

Alkyl Halides

26

Energy required to break a C-H bond
decreases as substitution on the carbon
increases.

Stability: 3° > 2 ° > 1° > methyl
H(kcal) 91, 95, 98, 104

Free Radical Stabilities

C

+

CH

3

CH

3

C

H

3

C

+

CH

3

H

C

H

3

C

+

H

H

C

H

3

C

+

H

H

H

Alkyl Halides

27

Substitution Reactions

• The halogen atom on the alkyl halide is

replaced

with another group.

• Since the halogen is more electronegative

than carbon, the

C-X

bond breaks

heterolytically and

X

-

leaves.

• The group replacing X

-

is a

nucleophile.

=>

C C

H X

+ Nuc:

-

C C

H Nuc

+ X:

-

Alkyl Halides

28

Elimination Reactions

• The alkyl halide loses halogen as

a halide

ion, and also loses

H

+

on the adjacent

carbon to a base.

• A

pi bond

is formed. Product is

alkene

.

• Also called

dehydrohalogenation (-HX).

=>

C C

H X

+ B:

-

+ X:

-

+ HB

C C

Alkyl Halides

29

S

N

2 Mechanism

• Bimolecular

nucleophilic substitution.

• Concerted reaction

: new bond forming

and old bond breaking at same time.

•

Rate is first order in each reactant.

Rate is first order in each reactant.

• Walden inversion.

=>

C

H

Br

H

H

H O

C

HO

Br

H

H

H

C

HO

H

H

H

+ Br

-

Alkyl Halides

30

S

N

2 Energy Diagram

• One-step reaction

.

• Transition state is highest in energy. =>

Alkyl Halides

31

Alkyl Halides

32

7_104.exe

S

N

2 reaction of oxonum ion

7_108.exe

Reaction of alcohols with thionyl chloride

Alkyl Halides

33

Steric

Hindrance

Relative rate of reaction for some alkyl halides

Alkyl Halide Type of C

Relative Rate

H

CH

2

X

methyl

30

CH

3

CH

2

X

primary

1

CH

3

CH

2

CH

2

X

primary 0.4

CH

3

CH

2

CH

2

CH

2

X

primary

0.4

(CH

3

)

2

CHX

secondary

0.025

(CH

3

)

3

CX

tertiary

~0.00

Size of
nucleophile
and hindrance

Rate = Ze

Rate = Ze

-

-

Ea/RT

Ea/RT

Alkyl Halides

34

Uses for S

N

2 Reactions

• Synthesis of other classes of compounds.
• Halogen exchange reaction.

=
>

Alkyl Halides

35

S

N

2: Nucleophilic Strength

• Stronger nucleophiles react faster.
• Strong bases are strong nucleophiles,

but not all strong nucleophiles are basic.

=>

Alkyl Halides

36

Trends in Nuc. Strength

• Of a conjugate acid-base pair, the

base

is stronger:

OH

-

> H

2

O, NH

2-

> NH

3

• Decreases

left to right

on Periodic Table. More

electronegative atoms less likely to form new bond:

OH

-

> F

-

, NH

3

> H

2

O

• Increases

down Periodic

Table, as size and

polarizability increase:

I

-

> Br

-

> Cl

-

=>

Alkyl Halides

37

Polarizability Effect

=
>

Alkyl Halides

38

Bulky Nucleophiles

Sterically hindered for attack on

carbon, so weaker nucleophiles.

CH

3

CH

2

O

ethoxide (unhindered)

weaker base, but stronger nucleophile

C

CH

3

H

3

C

CH

3

O

t-butoxide (hindered)

stronger base, but weaker nucleophile

=>

Alkyl Halides

39

Solvent Effects (1)

Polar protic solvents

(O-H or N-H) reduce

the strength of the nucleophile.
Hydrogen bonds must be broken before
nucleophile can attack the carbon.

=
>

Alkyl Halides

40

Solvent Effects (2)

• Polar

aprotic

solvents (no O-H or N-H) do

not form hydrogen bonds with nucleophile

• Examples:

CH

3

C N

acetonitrile

C

O

H

3

C

CH

3

acetone

=>

dimethylformamide

(DMF)

C

H

O

N

CH

3

CH

3

Alkyl Halides

41

Crown Ethers

• Solvate the

cation

, so

nucleophilic strength
of the anion increases.

• Fluoride becomes a

good nucleophile.

O

O

O

O

O

O

K+

18-crown-6

CH

2

Cl

KF, (18-crown-6)

CH

3

CN

CH

2

F

=>

Alkyl Halides

42

S

N

2: Reactivity of Substrate

• Carbon must be

partially positive

.

• Must have a

good leaving group

• Carbon must

not be sterically hindered

.

=>

Alkyl Halides

43

Leaving Group Ability

• Electron-withdrawing
• Stable once it has left (not a strong base)
• Polarizable to stabilize the transition state.

=>

Alkyl Halides

44

Structure of Substrate

• Relative rates for S

N

2:

CH

3

X > 1° > 2°

>> 3°

• Tertiary halides do not react via the

S

N

2 mechanism, due to steric

hindrance. =>

Alkyl Halides

45

Stereochemistry of S

N

2

Walden inversion

=>

Alkyl Halides

46

S

N

1 Reaction

• Unimolecular

nucleophilic substitution.

• Two step reaction

with carbocation

intermediate.

• Rate is first order

in the alkyl halide,

zero order in the nucleophile.

• Racemization

occurs.

=>

Alkyl Halides

47

S

N

1 Mechanism (1)

Formation of carbocation (slow)

(CH

3

)

3

C Br

(CH

3

)

3

C

+

+ Br

-

=>

Alkyl Halides

48

S

N

1 Mechanism (2)

• Nucleophilic attack

(CH

3

)

3

C

+

+ H O H

(CH

3

)

3

C O H

H

(CH

3

)

3

C O H

H

H O H

+

(CH

3

)

3

C O H + H

3

O

+

=>

• Loss of H

+

(if needed)

Alkyl Halides

49

S

N

1 Energy Diagram

• Forming the

carbocation is
endothermic

• Carbocation

intermediate is in
an energy well.

=>

Alkyl Halides

50

7_106.exe

S

N

1 with hindrance

7_105.exe

S

N

1 and S

N

2 reactions of alcohols with acids

7_107.exe

Racemic from S

N

1

Alkyl Halides

51

Rates of S

N

1 Reactions

• 3° > 2° > 1° >> CH

3

X

Order follows stability of carbocations

(opposite to S

N

2)

More stable ion requires less energy to

form

• Better leaving group, faster reaction (like

S

N

2)

• Polar protic solvent best: It solvates ions

strongly with hydrogen bonding.

=>

Alkyl Halides

52

Stereochemistry of S

N

1

Racemization:

inversion and retention

=>

Alkyl Halides

53

Rearrangements

• Carbocations can rearrange to form a

more stable carbocation.

• Hydride shift: H

-

on adjacent carbon

bonds with C

+

.

• Methyl shift: CH

3-

moves from adjacent

carbon if no H’s are available.

=>

Alkyl Halides

54

Hydride Shift

CH

3

C

Br

H

C

H

CH

3

CH

3

CH

3

C

H

C

H

CH

3

CH

3

CH

3

C

H

C

H

CH

3

CH

3

CH

3

C

H

C
CH

3

CH

3

H

CH

3

C

H

C
CH

3

CH

3

H

Nuc

CH

3

C

H

C
CH

3

CH

3

H Nuc

=>

Alkyl Halides

55

Methyl Shift

CH

3

C

Br

H

C

CH

3

CH

3

CH

3

CH

3

C

H

C

CH

3

CH

3

CH

3

CH

3

C

H

C

CH

3

CH

3

CH

3

CH

3

C

H

C
CH

3

CH

3

CH

3

CH

3

C

H

C
CH

3

CH

3

CH

3

Nuc

CH

3

C

H

C
CH

3

CH

3

CH

3

Nuc

=>

Alkyl Halides

56

S

N

2 or S

N

1?

• Primary or methyl

• Strong nucleophile

• Polar aprotic

solvent

• Rate = k[halide]

[Nuc]

• Inversion at chiral

carbon

• No rearrangements

• Tertiary

• Weak nucleophile (may

also be solvent

)

• Polar protic solvent,

silver salts

• Rate = k[halide]

• Racemization of

optically active

compound

• Rearranged products

=>

Alkyl Halides

57

E1 Reaction

• Unimolecular elimination
• Two groups lost (usually X

-

and H

+

)

• Nucleophile acts as base
• Also have S

N

1 products (mixture)

=>

Alkyl Halides

58

E1 Mechanism

• Halide ion leaves, forming carbocation.

• Base removes H

+

from adjacent carbon.

• Pi bond forms. =>

H C

H

H

C
CH

3

CH

3

Br

C

H

H

H

C CH

3

CH

3

O

H

H

C

H

H

H

C CH

3

CH

3

C C

H

CH

3

CH

3

H

+ H

3

O

+

Alkyl Halides

59

A Closer Look

O

H

H

C

H

H

H

C CH

3

CH

3

C C

H

CH

3

CH

3

H

+ H

3

O

+

=>

Alkyl Halides

60

E1 Energy Diagram

• Note: first step is same as S

N

1

=
>

Alkyl Halides

61

E2 Reaction

• Bimolecular

elimination

• Requires a

strong base

• Halide leaving and proton

abstraction happens
simultaneously - no intermediate.

=>

Alkyl Halides

62

E2 Mechanism

H C

H

H

C
CH

3

CH

3

Br

C C

H

CH

3

CH

3

H

O

H

+ H

2

O B

r

-

+

=
>

Alkyl Halides

63

Saytzeff’s Rule

• If more than one elimination product is

possible, the

most-substituted

alkene is the

major product (most stable).

• R

2

C=CR

2

>R

2

C=CHR>RHC=CHR>H

2

C=CHR

tetra > tri > di > mono

C C

Br

H

C

H

CH

3

H

H

H

CH

3

OH

-

C C

H

H

C

H H

CH

3

CH

3

C

H

H

H

C

H

C

CH

3

CH

3

+

=>

minor

minor

major

major

Alkyl Halides

64

E2 Stereochemistry

=>

Alkyl Halides

65

E1 or E2?

• Tertiary > Secondary
• Weak base
• Good ionizing

solvent

• Rate = k[halide]
• Saytzeff product
• No required

geometry

• Rearranged products

• Tertiary > Secondary
• Strong base required
• Solvent polarity not

important

• Rate = k[halide][base]
• Saytzeff product
• Coplanar leaving

groups (usually anti)

• No rearrangements

=>

Alkyl Halides

66

Substitution or Elimination?

• Strength

of the nucleophile determines

order: Strong nuc. will go S

N

2 or E2.

• Primary

halide

usually S

N

2.

• Tertiary halide

mixture of S

N

1, E1 or E2

• High

temperature

favors elimination.

• Bulky

bases

favor elimination.

• Good nucleophiles, but weak bases,

favor substitution. =>

Alkyl Halides

67

Secondary Halides?

Mixtures of products are common.

=
>

Alkyl Halides

68

End of Unit 5