Aryl halide and vinyl halide

Aryl Halides
Aryl halides are halides in which the
halogen is attached directly to an aromatic
ring.

Carbon-halogen bonds in aryl halides are
shorter and stronger than carbon-halogen
bonds in alkyl halides.

X
Whats the Difference Between Ar- and Ph-?
P h e n
y
l r e f e r s s p e c i f i c a l l y t o t h i s :
A r y l i s a g e n e r a l t e r m f o r a l l a r o m a t i c r i n g s y s t e m s :
C
N
N
O
Nomenclature
Aryl halides are named by prefixing the name of the halogen to
benzene. For example:
Numbering of the ring begins at the halogen-substituted carbon and
proceeds in the direction of the next substituted carbon that possesses the
lower number.

Ortho, meta or para ?

Mono-substituted aryl halides are characterised using the prefix ortho (o-), meta (m-
) or para (p-) depending on the placement of the substituent from the halogen or the
halogen from a higher priority functional group: 1,2-, 1,3- or 1,4- respectively.
Cl
1-chloro-2-ethylbenzene
or
o-ethylchlorobenzene
Cl
1-chloro-3-ethylbenzene
or
m-ethylchlorobenzene
Cl
1-chloro-4-ethylbenzene
or
p-ethylchlorobenzene
Cl
O
N
Br
I
Br
Br Br
Br
OMe
O
Cl
1-(3-chlorophenyl)ethanone
4-bromo-N,N-dimethylaniline
(E)-1-iodo-2-(prop-1-enyl)benzene
1,2,3-tribromobenzene
2-bromobiphenyl
methyl 2-(3-chlorophenyl)acetate
Physical properties

The physical properties of unsubstituted aryl halides are much like
those of the corresponding alkyl halides.

Thus, boiling points, melting points, and solubilities of aryl halides
are very similar to those of alkyl halides containing the same
number of carbon atoms.

Boiling points

Chlorobenzene, bromobenzene and iodobenzene are all oily liquids.
The boiling points increase as the halogen atom gets bigger.


Compounds boiling point (C)
C
6
H
5
Cl 132
C
6
H
5
Br 156
C
6
H
5
I 189


The main attractions between the molecules will be van der Waals
dispersion forces.

These increase as the number of electrons in the molecule increases. This
is the reason that the boiling points increase as the halogen atom gets
bigger.

There will also be permanent dipole-dipole attractions involved in the
chlorobenzene and bromobenzene, but very little in the iodobenzene.
Iodine has much the same electronegativity as carbon.


Solubility in water
The aryl halides are insoluble in water. They are denser than water and
form a separate lower layer.

The molecules are quite large compared with a water molecule. In order
for chlorobenzene to dissolve it would have to break lots of existing
hydrogen bonds between water molecules and also have to break the
quite strong van der Waals dispersion forces between chlorobenzene
molecules. Both of these cost energy.

The only new forces between the chlorobenzene and the water would
be van der Waals dispersion forces.

These aren't as strong as hydrogen bonds (or the original dispersion
forces in the chlorobenzene), and so wouldn't get much energy
released when they form.

It simply isn't energetically profitable for chlorobenzene (and the others)
to dissolve in water.

Resonance Picture
C-X bonds in aryl halides have more double
bond character than C-X bonds in alkyl halides
Synthesis of Aryl Halides
The two most common methods of preparing aryl
halides are by direct halogenation of benzene
and via diazonium salt reactions.




Preparing chlorobenzene and bromobenzene by reacting
chlorine or bromine with benzene, and
preparing iodobenzene from benzenediazonium chloride.
Preparation of Chlorobenzene

Benzene reacts with chlorine in the presence of a catalyst, replacing one of
the hydrogen atoms on the ring by a chlorine atom.

The reaction happens at room temperature. The catalyst is either aluminium
chloride or iron.

Strictly speaking iron isn't a catalyst, because it gets permanently changed
during the reaction. It reacts with some of the chlorine to form iron(III)
chloride, FeCl
3
.

The reaction between benzene and chlorine in the presence of either
aluminium chloride or iron gives chlorobenzene.

Preparation of Bromobenzene

The reaction between benzene and bromine in the presence of either
aluminium bromide (rather than aluminium chloride) or iron gives
bromobenzene.

Iron is usually used because it is cheaper and more readily available. If
we use iron, it is first converted into iron(III) bromide by the reaction between
the iron and bromine.
Preparation of Iodobenzene

Iodobenzene can be made from the reaction of benzene with iodine if they
are heated under reflux in the presence of concentrated nitric acid, but it is
normally made from benzenediazonium chloride solution. That's what we will
concentrate on here.

If you add cold potassium iodide solution to ice-cold benzenediazonium
chloride solution, nitrogen gas is given off, and you get oily droplets of
iodobenzene formed.

There is a simple reaction between the diazonium ions present in the
benzenediazonium chloride solution and the iodide ions from the potassium
iodide solution.

Primary
Arylamine
Aryl Diazonium
Salt
N
H H
N
NaNO
2
HCl, H
2
O
N
KI
room
temp.
Aryl Iodide
I
Me Me
Me
Cl
o-toluidine
Sandmeyer reaction

A second method for preparing aryl halides is the Sandmeyer reaction.

During a Sandmeyer reaction, a diazonium salt reacts with copper (I)
bromide, copper (I) chloride, or potassium iodide to form the respective aryl
halide.

The diazonium salt is prepared from aniline by reaction with nitrous acid at
cold temperatures.

Primary
Arylamine
Aryl Diazonium
Salt
N
H H
N
NaNO
2
HCl, H
2
O
N
CuCl
heat
Aryl Chloride
Cl
N
+
O

O
N
+
O

O
N
+
O

O
Cl
An aromatic (or heterocyclic) amine quickly reacts with a nitrite to form an
aryl diazonium salt, which decomposes in the presence of copper(1) salts,
such as copper (1)b chloride, to form the desired aryl halide.The reaction is
a radical nucleophilic aromatic substitution
Reactions of alkyl halides

1. S
N
2 NR
2. E2 NR
3. organo metallic compounds similar
4. reduction similar
C C X
X
aryl halide
vinyl halide
Ag+
-
OH
-
OR
NH
3
-
CN
ArH
AlCl
3
NO REACTION
Bond Lengths ()

CCl CBr
CH
3
X 1.77 1.91
C
2
H
5
X 1.77 1.91 sp
3

(CH
3
)
3
CX 1.80 1.92
CH
2
=CHX 1.69 1.86
C
6
H
5
X 1.69 1.86

sp
2

In aryl halides, the carbon to which the halogen is attached is sp
2

hybrizided. The bond is stronger and shorter than the carbon-
halogen bond in aliphatic compounds where the carbon is sp
3

hybridized.
Hence it is more difficult to break this bond and aryl halides resist
the typical nucleophilic substitution reactions of alkyl halides.
The same is true of vinyl halides where the carbon is also sp
2

hybridized and not prone to nucleophilic substitution.
In a manner analogous to the phenols & alcohols, we have the
same functional group in the two families, aryl halides and alkyl
halides, but very different chemistries.
Aryl halides, reactions:
1. Formation of Grignard reagent
2. EAS (Electrophilic aromatic substitution)
3. Nucleophilic aromatic substitution (bimolecular displacement)
(Ar must contain strongly electron withdrawing groups ortho and/or
para to X)
4. Nucleophilic aromatic substitution (elimination-addition)
(Ring not activated to bimolecular displacement)
1) Preparation of Grignard reagent
Br
Cl
Mg
Mg
anhyd. Et
2
O
THF
MgBr
MgCl
Overall an electrophilic aromatic susbtitution (EArS) can be
represented as follows:
2) EAS
There are three fundamental components to an electrophilic aromatic
substitution mechanism:

1. formation of the new bond from a C=C in the arene nucleophile
2. removal of the proton by breaking the C-H bond
3. reforming the C=C to restore the aromaticity
The mechanism is represented by the following series of events:

1.Formation of the reactive electrophile, E
+
from the reagents.

2.Slow reaction of the arene C=C with the E
+
to give a resonance
stabilised carbocation.

3. Loss of H
+
from the carbocation to restore the C=C and the
aromatic system
The reaction of the electrophile E
+
with the arene is the slow step since
it results in the loss of aromaticity even though the resulting cation is
still resonance stablised. This carbocation is also described as
the cyclohexdienyl cation or arenium ion or as a sigma-complex.
Electrophilic Aromatic Substitution of Aryl Halides

1. Aryl halides are themselves reactive towards EAS but they are less reactive
than benzene.
2. This is because halides

are weak deactivators
3. Halides direct subsequent reactions ortho, para.
4. This makes them a little unusual (activators are usually ortho, para-directing,
deactivators meta-directing).
5. The weak deactivation is due to the electronegativity of the halogen making the
intermediate cations less stable than those produced when benzene undergoes
substitution:
The directing effect is due to the resonance stabilisation of the cationic
intermediates derived by ortho or para attack but not by meta attack. For
example, the stabilisation during ortho attack is shown below :


However, aryl halides can undergo many of the same electrophilic
aromatic substitution reactions that benzene can
including nitration, sulfonation, further halogenation and Friedel-
Crafts alkylation or acylation reactions.
The X group is electron-withdrawing and
deactivating in EAS, but is an ortho/para
director.
Br
HNO
3
, H
2
SO
4
H
2
SO
4
,SO
3
Br
2
,Fe
CH
3
CH
2
-Br, AlCl
3
+
+
+
+
Br
Br
Br
Br
Br
Br
NO
2
SO
3
H
Br
CH
2
CH
3
Br
NO
2
Br SO
3
H
Br CH
2
CH
3


Aryl halides and vinylic halides are relatively unreactive toward
nucleophilic substitution under conditions that give facile nucleophilic
substitution with alkyl halides.
Reason:

(1) Phenyl cations are very unstable.
(2) Halogen bonds of aryl (and vinylic) halides are shorter and
stronger than those of alkyl, allylic, and benzylic halides because
of the hybridized state and the resonance.
But aryl halides can be remarkably reactive toward nucleophiles
if they bear certain substituents or when we allow them to react
under the proper conditions.
3) Nucleophilic aromatic substitution (bimolecular
displacement)
Chapter 21 32
Aryl Halides and Nucleophilic Aromatic
Substitution
Simple aryl and vinyl halides do not undergo
nucleophilic substitution







Back-side attack required for S
N
2 reaction is blocked
in aryl halides


Chapter 21 33
S
N
2 reaction also doesnt occur in aryl (and vinyl
halides) because the carbon-halide bond is shorter
and stronger than in alkyl halides
Bonds to sp
2
-hybridized carbons are shorter, and
therefore stronger, than to
sp
3
-hybridized carbons
Resonance gives the carbon-halogen bond some double
bond character
bimolecular displacement (nucleophilic aromatic substitution)
mechanism:
1)
+ :Z X
X
Z
RDS
X
Z
2)
Z
+ :X
X
Z
Z
X
Z
X
Z
X
Z
X
Z
X
G
G
If G is an electron withdrawing group in the ortho and
para positions, it will stabilize the intermediate anion.
NUCLEOPHILIC AROMATIC SUBSTITUTION BY ADDITION
ELIMINATION: THE SNAr MECHANISM
Nucleophilic substitution can occur when strong electron-withdrawing groups
are ortho or para to the halogen atom.

Cl
NO
2
OH
NO
2
+ OH
-
aq. NaHCO
3
130
H
+
Cl
NO
2
NO
2
OH
NO
2
NO
2
+ OH
-
aq. NaHCO
3
100
H
+
Cl
NO
2
NO
2
O
2
N
OH
NO
2
NO
2
O
2
N
+ OH
-
aq. NaHCO
3
35
H
+
The temperature
is related to the
number of ortho or
para nitro groups
But the meta-nitro group does not produce a similar activating effect.
Mechanism:

Cl
NO
2
+ OH
-
addition
slow
OH Cl
NO
2
elimination
fast
OH
-
+ Cl
-
O
-
NO
2
OH
NO
2
+ Cl
-
HO
Cl
N
O O
HO
Cl
N
O O
HO
Cl
N
O O
HO
Cl
N
O O
The delocalized carbanion is stabilized by electron-withdrawing groups in the
positions ortho and para to the halogen atom.
CF
3
Cl
NaNH
2
NH
3
CF
3
NH
2
m-(Trifluoromethyl)aniline
(-
Addition-Elimination Mechanism
Two step mechanism:

Step 1
nucleophile attacks aryl halide and bonds to the
carbon that bears the halogen
(slow: aromaticity of ring lost in this step)

Step 2
intermediate formed in first step loses halide
(fast: aromaticity of ring restored in this step)

Addition-Elimination Mechanism
Addition-Elimination Mechanism
Step 1 - Addition
bimolecular
consistent with second-
order kinetics;

first order in aryl halide,
first order in nucleophile

Rate = k [CH
3
ONa] [arene]
Addition-Elimination Mechanism
Step 1 - Addition
intermediate is negatively
charged

formed faster when ring
bears electron-withdrawing
groups such as NO
2

because negative charge
is stabilized..
Reaction Involves an Anionic Intermediate
Stabilization of Addition Product
by Electron-Withdrawing Group
Rapid Collapse of Cyclohexadienyl
Anion Intermediate
Step 2 - Elimination
carbon-halogen bond breaking does not occur
until after the rate-determining step
electronegative F stabilizes negatively
charged intermediate
F > Cl > Br > I is unusual, but consistent
with mechanism
The Role of Leaving Groups
The Role of Leaving Groups
Cl
NO
2
OH
NO
2
Cl
NO
2
NO
2
OH
NO
2
NO
2
O
2
N
O
2
N
Cl
+ NaOH NR
350
o
C, 4500 psi
H
+
OH
15% NaOH, 160
o
C H
+
warm water
Cl
NO
2
NH
2
NO
2
Cl
NO
2
NO
2
NH
3
NO
2
NO
2
O
2
N
O
2
N
Cl
NH
2
NH
3
, 170
o
C
NH
3
, room temp.
NH
3
, Cu
2
O, 200
o
C, 900 psi
NO
2
NO
2
49
Nucleophilic Aromatic Substitution through an
Elimination-Addition Mechanism: Benzyne
Under forcing conditions, chlorobenzene can
undergo an apparent nucleophilic substitution with
hydroxide
Bromobenzene can react with the powerful base amide







Chapter 21 50
The reaction proceeds by an elimination-addition
mechanism through the intermediacy of a benzyne
(benzene containing a triple bond)

Chapter 21 51
A calculated electrostatic potential map of benzyne
shows added electron density at the site of the
benzyne p bond
The additional p bond of benzyne is in the same plane as the
ring






When chlorobenzene labeled at the carbon bearing
chlorine reacts with potassium amide, the label is
divided equally between the C-1 and C-2 positions
of the product
This is strong evidence for an elimination-addition
mechanism and against a straightforward S
N
2 mechanism

Chapter 21 53
Benzyne can be generated from anthranilic acid by
diazotization
The resulting compound spontaneously loses CO
2
and N
2

to yield benzyne
The benzyne can then be trapped in situ using a Diels-
Alder reaction










Phenylation

Acetoacetic esters and malonic esters can be phenylated by benzyne
generated in situ from bromobenzene
1. Preparation of vinyl halides
Example of a vinyl halide:
R
Cl
Cl
Example of an aryl halide:
a. Halogenation of alkynes
b. Hydrohalogenation of alkynes
c. Elimination in dihaloalkanes
d. S
E
Ar - halogenation
2. Elimination in aryl and vinyl halides
These reactions never proceed by E1 because of low stability of aryl and vinyl carbocations.
Vinyl halides are much less reactive in E2, than alkyl halides because of a stronger
C(sp
2
)-Cl bond .
R
Br
KOH, 200
o
C
R H
Cl
O
NaOCH
3
H
3
CO
O
-
OCH
3
Cl
O
- H
3
CO
3. Substitution in vinyl halides
This reaction proceeds through addition, followed by elimination. It
never goes via S
N
2, because of the lack of stabilization of the transition
state.
(Same reason, why vinyl cations are less stable, than alkyl cations.)
Write a structural formula for each of the following:

(a)m-Chlorotoluene
(b)1-Chloro-1-phenylethane
(c)p-Bromobenzyl chloride
(d) 2-Chloronaphthalene
(e) 1,8-Dichloronaphthalene
(f) 2-Bromo-1-chloro-4-nitrobenzene
Latihan
Reactions Involving Aryl Halides
Electrophilic aromatic substitution
Bromobenzene
Br Br
BrOH
(hypobromous
acid)
Br
Br
Br
Br
Br
35.7% 1.0% 64.3%
halide substituents are ortho-para directing & deactivating
Reactions Involving Aryl Halides
Electrophilic aromatic substitution (Section 12.14)

ADD DDT SYNTHESIS
Reactions Involving Aryl Halides
Formation of aryl Grignard reagents (Section 14.4)
Bromobenzene
Br
MgBr
Mg
Et
2
O
Phenylmagnesium
bromide
Substitution Reactions Involving Aryl Halides
We have not yet seen any nucleophilic substitution
reactions of aryl halides.

Nucleophilic substitution on chlorobenzene occurs so
slowly that forcing conditions are required.

Nucleophilic Substitution of Chlorobenzene
Cl OH
(97%)
1. NaOH, H
2
O
370C
2. H
+
This reaction does not proceed via SN2..
the S
N
2 is not reasonable because the
aromatic ring blocks back-side approach
of the nucleophile. Inversion is not
possible.
Why is Chlorobenzene Unreactive?
SN1 Also Unlikely:
Aryl Cations are Highly Unstable
Cl
C
Cl
S
N
1
empty
sp
2
orbital
Aryl Cation
SN1 not reasonable because:

1) CCl bond is strong; therefore, ionization to a carbocation is a
high-energy process

2) aryl cations are highly unstable
What is the Mechanism of This Reaction?
Cl OH
(97%)
1. NaOH, H
2
O
370C
2. H
+
23.5
Nucleophilic Substitution in
Nitro-Substituted Aryl Halides