Aromatic compounds

Aromatic Compounds

adjective
1.having a pleasant and distinctive smell.
2.relating to or denoting organic compounds containing a planar unsaturated ring
of atoms which is stabilized by an interaction of the bonds forming the ring, e.g.
benzene and its derivatives.
noun
1.a substance or plant emitting a pleasant and distinctive smell.
2.an aromatic compound.

The adjective "aromatic" is used by organic chemists in a rather different way than it
is normally applied. It has its origin in the observation that certain natural substances,
such as cinnamon bark, wintergreen leaves, vanilla beans and anise seeds, contained
fragrant compounds having common but unexpected properties. Cinnamon bark, for
example, yielded a pleasant smelling compound, formula C9H8O, named
cinnamaldehyde.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

If the compound below is reacted under the conditions shown,

what are the expected products.
?
+
H3O, H2O

KMnO4/HO
- 1 mole Br2,
? CCl4, dark
?
H2O, cold
25 oC

H2, Metal catalyst

?
Answer: No Reaction!!
This compound is benzene
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Discovery of benzene:
In 1825 English chemist Michael Faraday (Royal Institution) isolated benzene from a
compressed illuminating gas that had been made by pyrolyzing whale oil. Faraday called this
new hydrocarbon "bicarburet of hydrogen"; we now call it benzene.
From this point the study of the class of compounds that organic chemists call aromatic
compounds.
In 1834 the German chemist Eilhardt Mitscherlich (University of Berlin) synthesized benzene
by heating benzoic acid with calcium oxide. Using vapor density measurements Mitscherlich
further showed that benzene has the molecular formula C6H6.
In 1834 the German chemist Eilhardt Mitscherlich (University of Berlin) synthesized benzene
by heating benzoic acid with calcium oxide. Using vapor density measurements Mitscherlich
further showed that benzene has the molecular formula C6H6.
heat C6H6 + CaCO3
C6H5COOH + CaO
benzene

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

• First isolated in 1825 by Michael Faraday by pyrolysis of

whale oil; was characterized as a ―CH‖ compound.
• Later shown that benzene has a molecular formula of C6H6
(1834), a m. p of 5.5 oC, a b. p of 80.1 oC, and at room
temperature is a colorless liquid.
• It is chemically inert under many reaction conditions; in fact, it
is so inert that benzene has been widely used as an industrial
and laboratory-scale organic solvent.
• Proposal of a structure for benzene was a major under-taking,
but it revolutionized chemistry.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

III. The Stability of Benzene

Demonstrated by examining heats of hydrogenation of cyclohexene,
cyclohexadiene, and benzene.

Pt
+ H2 ∆Ho = -120 kJ mol-1

Calculated:
∆Ho = (2 x -120) = -240 kJ mol-1
+ 2H2 Pt
Observed:
∆Ho = -232 kJ mol-1
Calculated:
Pt ∆Ho = (3 x -120) = -360 kJ mol-1
+ 3H2 Observed: ∆Ho = -208 kJ/mol-1
Difference: 152 kJ/mol
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Resonance Energy of Benzene: 152 kJ mol-1

The difference between the amount of heat released upon
hydrogenation of benzene (actual value) and that predicted for
hydrogenation of 1,3,5-cyclohexatriene (theoretical value).

• So, benzene is 152 kJ/mol more stable than would be

predicted based on the Lewis structure of the mythical
1,3,5-cyclohexatriene.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

• These thermochemical calculations provide an explanation for

the stability of benzene under addition reaction conditions.
• Quantum mechanics gives the best explanation for benzene‘s
unusual properties and the modern theory for its structure.

+ 3H2
...................
Potential Energy

152
+ 2H2 kJ/mol
+ H2 ...................
Ho = -232 Benzene
kJ/mol
Ho = -120 + 3H2
kJ/mol Ho = -262
kJ/mol Ho = -208
kJ/mol

Cyclohexane
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Benzene structure:
•Elementary analysis and molecular weight of benzene proved that benzene has molecular
formula C6H6.
•Benzene underwent addition reaction with bromine or chlorine in sun light to give
C6H6X6 (X=Br or Cl).
•Catalytic hydrogenation of benzene give C6H12 (cyclohexane) by addition of 3 mole of
hydrogen.
•Benzene underwent electrophelic substitution reaction in the presence of catalyst to give
mono substituted benzene C6H5X.
•Benzene produce three isomers when the substitution reaction carried with two moles of
reagents in the presence of catalyst to give C6H4X2.
C 6H 6 X 6 Br2 or Cl2
X2/FeX3
From these evidence (X = Br or Cl) C 6 H 5X
sun light heat
Kekule conclude that (h) monohalobenzene
cyclohexane 3H2/Ni X = Br or Cl
the structure of C 6H 6
benzene is: C6H12 Benzene

Three isomers C 6 H 4X 2 X2/FeX3 H2SO4 C6H5SO3H

heat Benzene sulfonic acid

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The Kekulé Structure of Benzene

A. Proposal of the first accepted structure for benzene
• Based on the structural theory
• Structural theory states:
1. Atoms of the elements can form a fixed number of bonds (carbon is
tetravalent
2. A carbon atom can use one or more of its valences to form a bond to
another atom
• The first accepted structure for benzene was proposed in 1865 by F.
August Kekulé:
1. Carbon atoms arranged in a 6-membered ring
2. Carbon atoms are bonded by alternating single and double bonds.
H
3. One H atom is attached to each C atom: H H

All H atoms of benzene are equivalent or

H H
H
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

FRIEDRICH AUGUST KEKULÉ

(7th September 1829–13th July 1896

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Problem Kekulé structure:

predicts two different 1,2-dibromobenzenes
H Br H H
H H H Br H Br H H
2Br 2/FeBr 3 2Br2/FeBr3
H H H H H Br H H
H H H H

Experimentally only one 1,2-dibromobenzene has ever been found.

Possible Solution: (Kekulé in 1872) suggest that equilibrium
between the two structures so rapid that separation of two
isomers is impossible. Br Br

Br Br

• Now known to be incorrect

Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds
Resonance Theory
Kekulé proposed two structures for benzene:
Resonance theory states: whenever two or more Lewis structures differ only in the
positions of their electrons, no individual
Each Lewis structure is a resonance contributor to the actual structure of the molecule
(resonance hybrid).

1.39 Ao
Resonance 120o H
Conclusions from resonance theory: hybrid H H
Bonds are neither single nor double (all bonds are 1.39 Å in length).
All bond angles are 120o. H H
All six electrons are delocalized about the six carbon atoms of the ring. H
Resonance theory also states: whenever two equivalent resonance structures can be
drawn, the molecule is much more stable than any of the individual resonance
contributors. This explains the resonance ―stabilization‖ energy of benzene
calculated from thermochemical measurements (152 kJ/mol)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Problem Kekulé structure:

H2SO4 No Reaction

heat Br2
C6H5COOH C6H6 No Reaction
CaO benzene
Benzoic acid

KMnO4
No Reaction

Benzene also proved unreactive to common double bond transformations, as shown below.
For comparison, reactions of cyclohexene, a typical alkene, with these reagents are also
shown. As experimental evidence for a wide assortment of compounds was acquired, those
incorporating this exceptionally stable six-carbon core came to be called "aromatic".
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

OSO3H
H2SO4 H
H
H Br
Br2 H
H
Br
KMnO4 COOH
COOH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Stability of benzene:
If benzene is forced to react by increasing the temperature and/or by addition of a
catalyst, It undergoes substitution reactions rather than the addition reactions that
are typical of alkenes.
This further confirms the previous indication that the six-carbon benzene core is
unusually stable to chemical modification.
The conceptual contradiction presented by a high degree of unsaturation (low H:C
ratio) and high chemical stability for benzene and related compounds remained an
unsolved puzzle for many years.
Eventually, the presently accepted structure of a regular-hexagonal, planar ring of
carbons was adopted, and the exceptional thermodynamic and chemical stability of
this system was attributed to resonance stabilization of a conjugated cyclic triene.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Huckel ruke:

In 1931, Huckel proposed that any compound with a cyclic, conjugated p-system
containing 4n+2 electrons, where n is any integer, will display enhanced stability (like
benzene), while any compound with a cyclic, conjugated p- system containing 4n
electrons will display reduced stability like cyclobutadiene).
Hückel's rule, however, suffers from some shortcomings. One is that it is not
quantifiable. According to Hückel's rule, a molecule is either aromatic or it is
not, and there is no way to determine, for example, how aromatic pyridine is
relative to benzene.
Secondly, Hückei's rule is based on an extremely simplified view of quantum theory,
and is theoretically deeply flawed. Finally, Hückel's rule does not account for the
behavior of large annulenes or polycyclic aromatic hydrocarbons.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
Hückel‘s Rule
A. Proposed in 1931 by the German physicist Erich Hückel for
compounds composed of one planar ring in which each atom
has a p orbital:
B. Planar monocyclic rings containing (4n + 2) p electrons have
closed shells of delocalized electrons-- just like benzene!
C. n = 0, 1, 2, 3,…….
So, planar, monocyclic rings with 2, 6, 10, 14, ….
delocalized electrons are aromatic.

Benzene [14]Annulene Cyclopentadienyl

4n + 2 = 6 4n + 2 = 14 Anion
n=1 n=3 4n + 2 = 6
n=1
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Laboratory methods of preparation of benzene:

1. By passing hydrocarbon gases (methane, ethane, propane, butane or hexane
through tube at elevated temperature:
CH CH pass througho C6H6
tube at 580 C

2. By heating sodium or potassium benzoate with soda lime:

Decarboxylation was happened to give benzene
fusion
C6H6CO2Na + NaOH/CaO
soda lime
C6H6 + Na2CO3
sodium benzoate
3. By heating phenol with zinc dust:
Reduction was happened to give benzene
heat
C6H6OH + Zn, powder C6H6 + ZnO
phenol
4. By hydrolysis of benzene sulphonic acid with super heated steam:
super heated steam
C6H6SO3H + C6H6 + H2SO4
benzene sulphonic
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Commercial sources of benzene and its derivatives:

Benzene and its derivatives are used as high octane gasoline.
Also are used as a staring materials for many chemical industries
such as; detergents, insecticides, polymers, dyes, drugs, …and so
on.
Before world war II the coal is the only source for aromatic
hydrocarbon, but after that the petroleum became the main
source

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

NOMENCLATURE OF BENZENE DERIVATIVES

Two systems are used in naming monosubstituted benzenes. In certain compounds, benzene
is the parent name and the substituent is simply indicated by a prefix. We have, for example,
F Cl Br NO2

Fluorobenzene Chlorobenzene Bromobenzene Nitrobenzene

For other compounds, the substituent and the benzene ring taken together may form a new
parent name. Methylbenzene is usually called toluene, hydroxybenzene is almost always
called phenol, and aminobenzene is almost always called aniline. These and other examples
are indicated here.
.. H
CH3 :O H :N H

Toluene Phenol Aniline

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

..
:O ..
SO3H CO2H C CH3 :O H

Benzenesulfonic acid Benzoic acid Acetophenone Anisole

When two substituents are present, their relative positions are indicated by the prefixes ortho,
meta, and para (abbreviated 0-, m-, and p-) or by the use of numbers. * For the
dibromobenzenes we have
Br
Br
Br

Br Br Br
1,2-Dibromobenzene 1,3-Dibromobenzene 1,4-Dibromobenzene
(o-dibromobenzene) (m-dibromobenzene) (p-dibromobenzene)
ortho meta para

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The dimethylbenzenes are called xylenes.

CH3
CH3
CH3

CH3 CH3 CH3

1,2-Dimethylbenzene 1,3-Dimethylbenzene 1,4-Dimethylbenzene

(o-xylene) (m-xylene) (p-xylene)

and for the nitrobenzoic acids:

CO2H
CO2H
CO2H

NO2 NO2 NO2

2-Nitrobenzoic acid 3-Nitrobenzoic acid 4-Nitrobenzoic acid
(o-nitrobenzoic acid) (m-nitrobenzoic acid) (p-nitrobenzoic acid)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

If more than two groups are present on the benzene ring, their positions must be
indicated by the use of numbers. As examples, consider the following two com-
pounds.
Numbers can be used for two or more substituents, but ortho, meta, and para must-
never be used for more than two.

Cl Br
1 1
Cl Br
6 6
2 2

5 5
3 3
4 Cl 4
Br
1,2,3- Trichlorobenzene 1,2,4- Tribromobenzene
(not 1,3,4-tribromobenzene)

We notice, too, that the benzene ring is numbered so as to give the lowest possible
numbers to the substituents.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

When more than two substituents are present and the substituents are different,
they are listed- in alphabetical order.
When a substituent is one that when taken together with the benzene ring gives a new
base name, that substituent is assumed to be in position 1 and the new parent name is
used:

COOH SO3H
1 1 F
6 6
2 2
5 5
O 2N 3 3
4 NO2 4
F
3,5-Dinitrobenzoic acid 2,4-DifluorobenzenesuIfonic acid

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

When the C6Hs- group is named as a substituent, it is called a phenyl group. A

hydrocarbon composed of one saturated chain and one benzene ring is usually named
as a derivative of the larger structural unit. However, if the chain is unsaturated, the
compound may be named as a derivative of that chain, regardless of ring size. The
following are examples: H C CH
3 CH CH3

CH2CH2CH2CH3

3,5-Dinitrobenzoic acid 2-Phenyl-2-butene

H3C CH CH2 CH2 CH2 CH2 CH3

2-Phenylheptane

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The phenyl group is often abbreviated as C6Hs-, Ph-, or ~-. The name benzyl is an
alternative name for the phenylmethyl group:

CH2 CH2 Cl

The benzyl group Benzyl chloride

(the phenylmethyl group) (phenylmethyl chloride)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Important Aromatic Compounds:

Benzenoid Aromatics:

CHO
COOH CHO

OCH3
OH
Benzoic Acid Vanillin Benzaldehyde

Plant Products

O O

OH OH

HO HO
OCH3
p-Coumaric acid Ferulic acid

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

O
O
O
-
Amino Acids O
- +
+NH NH3
HO
3
Amino Acids Tyrosine
Analgesics

NH CH3
NH CH3
HO O
Medicinal Agents
HO O
Acetaminophen Ibuprofen
H3C
NH
F3C
N
O

Fluoxetine
Cocaine (An antidepressant
(A local anesthetic)
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Reactions of benzene.
There are three main reactions of benzene:
i. Substitution reactions
ii. Addition reactions
iii. Oxidation reactions
i. Substitution reactions of benzene as we know the benzene
ring is flat planer shape and presented between two clouds of
electrons from up and dawn.
From this point the benzen was considered as nucleophile and
will be attacked by the electrophile.
All the substitution reactions of benzene are electrophelic
aromatic substitution (EAS) reactions.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Electrophilic Aromatic Substitution (EAS) Reactions:

i. A General Mechanism for EAS Reactions
ii. Halogenation of Benzene
iii. Nitration of Benzene
iv. Sulfonation of Benzene
v. Friedel-Crafts Alkylation
vi. Friedel-Crafts Acylation
vii. Limitations of Friedel-Crafts Reactions

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Electrophilic Aromatic Substitution (EAS) Reactions:

Usually a catalyst is needed to give electrophile
E H

+ E

Normally electrophilic attack leads to an addition reaction.

Addition to the ring would cause destruction of the aromaticity of the ring.

H E
E Y
Y

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

To prevent loss of aromaticity, a hydrogen is lost instead to give a net substitution

reaction.
H
E
E
+ E + H

The Reaction Mechanism of electrophilic aromatic substitution.

E H

+ E

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

• The electrophilic attack is very endothermic.

• The resultant cation is allylic but the aromaticity has been lost.
• The cation is highly resonance stabilized however.

H H H
E A E E +
+ +
E

Arenium ion (complex)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Decomposition of arenium ion intermediate

The second step completes the reaction by losing a proton and regenerating the
aromatic ring.
This step is very exothermic.
Once the product is formed it is difficult for this step to reverse itself.

A-
E H E
+
+ H A

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Free-Energy Diagram of EAS Reactions

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The Energy Diagram

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

1 -Halogenation
The halogens Cl2 or Br2 may be added to an arene in the presence of either FeCl3, for
chlorination, FeBr3 for bromination.

.. .. .. + .. + Br
..
Mechanism: :Br
.. Br
.. :+ FeBr3 :Br Br FeBr3 : + : FeBr3
Br
.. .. .. ..
Bromonium ion
The Iron complex is much more electrophilic than bromine itself and this permits attack
on the ring.
+ Br Br
.. + Slow
+ :Br
.. H H
+

.. Br
Br:
.. ..
:Br
.. H
+ +
H
..
Prof. Dr. Adel M. Kamal El-Dean :Br
.. FeBr3
Aromatic compounds

Electrophilic aromatic chlorination is analogous to electrophilic aromatic bromination.

Cl

Cl2
FeCl3

• But electrophilic aromatic iodination is different

I
HNO3
+ I2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

2. Nitration
Introduction of a nitro group as substituent is called nitration.
The reagent used to introduce the nitro group is a mixture of nitric acid and sulfuric
acid.
Sulfuric acid is a powerful dehydrating agent. (A substance that causes loss of water.)
Nitric acid when mixed with sulfuric acid will react to lose an OH group and form
water.
The loss of water leads to generate nitronium ion as the electrophile in the nitration
reaction.
.. ..
.. O: H O :
+
HO3SO H + H O
.. N .. + -
HSO4
H O N
.. .. +
..:
O O:
..

:O:
H2O + N+
:O:
Nitronium ion
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

:O: +
+

N+ H
+ H
:O: NO2 NO2

+ H
H +
NO2 NO2
+

NO2

HNO3
H2SO4

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

3. Sulfonation
Introduction of a sulfonic acid group into an aromatic compound is called sulfonation.
The reagent used to introduce a sulfonate group is called oleum (mixture of sulfuric acid
and sulfur trioxide, SO3).

.. :O: .. .. :O: .. .. :O: H .. :O: .. -

HO S O+ H + HO S O:
.. S O
HO .. H HO
.. S O .. H .. .. .. ..
:O: :O: ::
O :O:

+ .. :O: .. - ..O :OS : O.. .. :O: .. -

+ SO3 HO S O:
H3O + HO S O ..: .. + .. H
..
..:
H2O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

..O .. -
:O: .. : O..:
.. S
.. S ..O
O + H O:
..
HSO4-

.. ..
: ..
O :O ..
H2O + S OH S O:
.. ..
:..
O :O.. H +
OH2

SO3H
heat
SO3
H2SO4

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Friedel-Crafts Alkylation
R
AlCl3
+R X + HX
R = Alkyl

Mechanism:
.. ..Cl
: Cl : H3C : :
H3C ..+ - ..
.. .. Cl Al Cl:
Cl
Al .. .. ..
.. : :Cl
.. .. :
Cl H3C :Cl
.. :
H3C
..Cl
: :
.. - .. +
:Cl
.. Al Cl:
.. + H3C CH3
:Cl
..: Isopropyl carbocation

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Freidel-Crafts Alkylation
The introduction of an alkyl group to an aromatic ring is called alkylation.
The reagent most commonly used to perform alkylations is a mixture of an alkyl halide
and a Lewis Acid Catalyst.
Common Lewis Acid Catalysts are: AlCl3, BF3, SnCl4.
Alkyl Halides: If the alkyl halide is a 2º or 3º alkyl group the electrophile will be a
carbocation.
..
.. : + AlCl3
(CH3)3C Cl (CH3)3C Cl AlCl3 (CH3)3C + AlCl4

C(CH3)3
AlCl3
+ (CH3)3C Cl

If the alkyl halide is a 1º alkyl group the electrophile will be the Lewis acid complex.

..
CH3 Cl: + AlCl3 CH3 Cl AlCl3
..

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Friedel-Crafts Acylation

The introduction of acyl group to an arene is called acylation.

The reagents used to affect acylation are an acyl halide and aluminum chloride catalyst.
Reaction of the acyl halide with aluminum chloride produces an acylium ion.
COCH3
O
+ H3C C Cl AlCl3
80 oC
Acetyl chloride Acetophenone (97%)

The acylium ion is the electrophile in this reaction.

Preparation of Acid Chlorides:

O O
80 oC
H3C C OH + SOCl2 H3C C Cl + SO2 + HCl
Acetic Acid Thionyl Chloride Acetyl chloride
80-90%

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Anhydrides work as acylating agents:

O
H3C C COCH3
O
+ O AlCl3
H3C C OH
Remaining steps
H3C C + are analogous to
those in the general
O
Acetophenone (82-85%) and bromination
Acetic Anhydride
mechanisms.
• Product is a Lewis
O O acid-base complex,
R C Cl + AlCl3 RC O + AlCl3 O C R from which the free
ketone can be
liberated with
water.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Limitations of Friedel-Crafts Reactions

Cation rearrangements are common in Freidel-Crafts alkylation.
Sec-butylchloride rearranges to t-butyl cation. So sec-butyl benzene cannot be
prepared directly. H H
+
H3C C CH2 Cl + AlCl3 H3C C CH2 + AlCl4
CH3 CH3

The intermediate carbocation

rearranges to the more stable +
H3C C CH2 H
tertiary carbocation.
CH3

H3C CH3
+ C
H3C C CH2 H + CH3
CH3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

In the following scheme the 1o

intermediate carbocation
rearranged to the more stable
secondiary carbocation.
AlCl3
CH3CH2CH2Br CH3CH2CH2 Br AlCl3

CH3CH2CH2
BrAlCl3

Propylbenzene CH3CHCH3
H3C CH3
Minor
CH

Isopropylbenzene
Major

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

In order to overcome this limitation we can follow the

following strategy:
By using the combination of acylation followed by reduction
the compound can be prepared easily.

O H
H O
C C CH3
AlCl3
+ H3C C C Cl CH3
CH3

H H
O H
N2H2 C C CH3
C C CH3
CH3
KOH H CH3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Some Aryl Substrates are Unreactive toward alkylation:

Substrates such as; NO2, N=Me3, CO2H, COR, CF3, SO3H, NH2, NHR, NR2,
when attached to the benzene ring inhibits the progress of friedel-Crafts
reaction.

Y +
Y = NO2, -NMe3, CO2H, Freidel craft No reaction occurred
COR, CF3, SO3H, NH2, reaction or very difficultreaction
NHR, NR2

Either aryl or Vinyl Halides are not used as source of electrophiles in

Freidel-Craft reaction Cl

no reaction
AlCl3
Cl
no reaction

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Alkenes can also be used as the alkylating agent if a strong

nonnucleophilic acid like H2SO4 is used as the alkylating agent.
Sulfuric acid used to generate the carbocation as alkylatin agent

H3C C CH2 + H2SO4 H3C C CH2 H

CH3
CH3

C(CH3)3
H2SO4

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Polyalkylations
In some cases additional alkylation was occurred to form poly alkylated
derivatives. Polyalkylations
In some cases additional alkylation was occurred to form poly alkylated
derivatives.

CH3 CH3 CH3

CH3Cl
AlCl3
+ +
H3C
CH3 CH3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Addition reactions to benzene:

Reduction of benzene:
There are two different ways to reduce aromatic hydrocarbons: Birch
reduction or catalytically reduction

1 - Birch Reduction
a. The reaction involves reacting an aromatic ring system with sodium in liquid
ammonia containing an alcohol.
b. The product of the reaction is an isolated diene

Na/NH3
CH3OH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Mechanism:
The reaction begins in a manner similar to the reduction of an alkyne with a group I
metal in liquid ammonia.
An electron is transferred to the aromatic ring to form a radical anion is formed.
The radical anion then reacts with the alcohol by abstracting a proton.
Next a second electron is transferred to the racical to form a carbanion.
Finally step is abstraction of another proton from a second molecule of methanol to
give the product.
. ..
Na/NH3
..
H OCH3 H H
Na/NH3
H3CO H
H H
..

H H H H

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

2 - Catalytic hydrogenation
Catalytic hydrogenation can be performed using hydrogen in the presence of
catalysit.
Generally the reaction gives total reduction to the cycloalkane. The catalyst
usually used is either Platinum or Palladium metal.

CH3 CH3
CHCH3 CHCH3
H2
Pt

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

2 – Oxidation reactions of benzene

Benzene unreactive towards oxidizing agent like KMnO4, CrO3 or H2O2 but
can be oxidized by vanadium pentaoxide at high temeprature to give maleic
anhydride.
O
O2, V2O5
O maleic anhydride
400-440 oC

O
2 – Oxidation reactions of benzene
Also benzene oxidized by ozone to give triozonide which hydrolyzed to glyoxal.

O
O O CHO
O 2 , V 2O 5 OO H2O
3
400-440 oC O CHO
O
O Glyoxal
O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Effect of Substituents on Reactivity &

Orientation of EAS Reactions
Substituents have two effects on EAS reactions:
1. Activation or Deactivation
Activating substituents make EAS reactions faster;
deactivating substituents make EAS reactions slower.
2. Substituents control orientation of products.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Rate and Regioselectivity in electrophilic aromatic substitution.

A. Rate Effects
1. Groups attached to an aromatic ring will either cause substitution to occur
faster or slower than benzene itself.
i. A group that causes substitution to occur faster than benzene is called an
activating group.
ii. A group that causes substitution to occur slower than benzene is called a
deactivating group.
B. Activating Groups
a. Groups that can donate electron density to the aromatic ring also activate the
ring to substitution.
i. Alkyl groups stabilize carbocations by donating electron density to the
carbocation center.
ii. In the same way, alkyl groups speed electrophilic attack on an aromatic
ring by donating electron density to the ring.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

..
:OCH3 ..OCH
3

b. Groups with Nitrogen or Oxygen attached to the ring also activate the ring to
substitution.
i. In this case, the lone electron pairs on these two elements become directly
involved in resonance so donation is even better here.
ii. While this resonance contributer is not the major resonance contributer, it
does provide electron donation to the ring.
The activating groups in decreasing order are:
NH2 > NHR> NR2 > OH > NHCOR > OR > OCOR > R > Ar

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

C. Deactivating groups:
a. CF3 is a deactivating group.
i. Deactivation occurs because the C-F bond is polarized toward fluorine.
ii. This in turn makes the carbon electron deficient so that it will withdraw electrons
from the ring that it is attached to.
iii. Reduces the ability for electrophilic attack on the ring.
b. Halogens are only weakly deactivating.
i. The halogen itself is highly electronegative so that it strongly withdraws
electrons.
ii. The lone pair electrons though can interact with the ring through resonance
and thus donate electron density in this way.
iii. The net result is two opposing effects, one donating and one withdrawing.
The withdrawing effect wins out slightly.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

c. The deactivating groups in increasing order of deactivation are:

F < Cl < Br < I < CH2X < COH < COR < COCl < CN < SO3H < CF3 < NO2

E. Regiospecificity of Electrophilic Aromatic Substitution

1. A group attached to a benzene ring will direct a second group during attack
in one of two ways.
i. Some substituents will direct attack into the ortho or para postion.
ii. Some substituents will direct attack into the meta position.
2. Directing effects are related to the ability to donate electron density.
i. All electron donating groups are ortho – para directors.
ii. All electron withdrawing groups except halogens are meta directors.
iii. Halogens are ortho–para directors because of the ability to resonance
donate electrons even though their net effect is electron withdrawal.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Substituents have two effects on EAS products.

Orientation of EAS Reactions
CH3 CH3 CH3
NO2
HNO3 Activating
H2SO4 +
substituents are
o, p-directors
NO2

Cl Cl Cl
NO2 Mildly
HNO3
H2SO4 + Deactivating
halogens are
NO2
o,p-directors.
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Ortho-Para Directors Meta Directors

Strong Activators: Moderate

-NH2, -NHR, -NR2, -OH, -O- Deactivators:
Moderate Activators: -CN, -SO3H, -CO2H, -
-NHCOR, -NHCOAr,-OR, -OAr CO2R, -CHO, -COR

Weak Activators:
-R, -C6H5 Strong Deactivators:
Weak Deactivators: -NO2, N+R3, -CF3,
-F, -Cl, -Br, -I -CCl3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
Theory of Substituent Effects
on EAS Reactions
A. Effect of Electron-Releasing and Withdrawing Groups on Reactivity

+
Q + Q
Q Electron-releasing
+ substituent stabilizes
+E + transition state.
+
+
Reaction is faster.
H E H E
Q +
+
Q Q
Electron-withdrawing
+ Substituent
+E +
+ destabilizes transition
+ state. Reaction is
H E H E slower.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Electrostatic potential maps in Figure show differences in electron

density of the arenium ion when it is substituted with -CH3 or -CF3.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

1. Nitration of Toluene.

CH3 CH3 CH3

CH3
NO2
HNO3
+ +
Acetic
Anhydride
NO2
NO2
63% 3% 34%
2. Nitration of trifluoromethylbenzene.

CF3
CF3 CF3 CF3
NO2
HNO3
+ +
H2SO4
NO2
NO2
6% 91% 3%

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
Reaction Mechanism in the nitration of
CH3 CH3
toluene.
H
a. Look at the σ-complexes that result from NO2
+
NO2
attack by nitronium ion. +
i. Ortho attack:
The resonance contributor CH3 CH3 CH3
H H H
III has extra stability since +
NO2 NO2 NO2
the positive charge located + +
next to the electron donating
methyl group. I II III
CH3 CH3
+
NO2
+

H NO2
CH3 CH3 CH3
ii. Para attack:
+
As in the ortho attack. II plays the same
+ +
stability effect on the intermediate.
H NO2 H NO2 H NO2
I II III
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

iii. Meta attack:

CH3 CH3

+
NO2 H
No added stabilization is +
provided in any of the O 2N
resonance structures in
this case. CH3 CH3
CH3

+ +
H
H H
+
O2N O2N O2N

I II III

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

iv. Reactions characteristic for alkyl group:

Side chain oxidation:
COOH CH2CH3
Side chain with any length (1C, CH3
2C, 3C…etc) which usually KMnO4 KMnO4
aliphatic was oxidized with heat
heat
KMnO4 or K2Cr2O7 to
carboxylic group

Side chain halogenation: CH3 CH2Cl CHCl2 CCl3

Side chain was chlorinated free Cl2 Cl2 Cl2
radically substitution in the
h h
presence of UV or sun light. h

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

b. An Explanation of the results.

i. The rate-determining intermediates for ortho and para nitration each has
a resonance form that is a tertiary carbocation.
ii. All of the resonance forms for the rate-determining intermediate in meta
nitration are secondary carbocations.
iii. Tertiary carbocations, being more stable, are formed faster than
secondary ones.
iv. The intermediates for attack at the ortho and para positions are formed
faster than the intermediate for attack at the meta position.
v. Thus, the major products are o- and p-nitrotoluene.
c. Partial Rate Factors.
One way to look at Electrophilic Aromatic Substitution is by comparing the
rate of a given reaction at a particular site in a molecule to the rate of that
same reaction in benzene.
These rates are shown by writing a number that reflects the rate of that
position relative to benzene.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

CH3

42 42
2.5 2.5
58
How to use partial rate factors. Nitration of toluene vs. t-butylbenzene.
a. Because the t-butyl group is activating all positions are accelerated relative to
benzene.
b. The ortho position is far less activated in t-butyl- benzene compared to
toluene reflecting the steric hindrance created by the t-butyl group.
CH3
H3C C CH3
CH3
42 4.5 4.5
42
2.5 2.5 3 3
58 75
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

d. The mechanism of the nitration of trifluoromethylbenzene.

a. Look at the σ-complexes that result from attack by
nitronium ion.
i. Ortho attack: CF 3 CF 3
+
H
NO2
NO2
+
The resonance
contributor III is CF 3 CF 3 CF 3
H H
destabilizing due to the H
+
positive charge location NO2 NO2 NO2
+ +
next to the electron
withdrawing
I II III
trifluoromethyl group.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

ii. Para attack: CF 3

CF 3

+
Like the ortho case, the NO2
+
resonance contributor II
is destabilizing because H NO2
the charge is located CF 3 CF 3 CF 3
next to the
+
trifluoromethyl group.
+ +

H NO2 H NO2 H NO2

I II III

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

iii. Meta attack:

CF 3
CF 3
No destabilization
+ H
occurs in any of NO2
+
the resonance O2N
structures for
meta substitution. CF 3 CF 3 CF 3

+ +
H H H
+
O2N O2N O2N

I II III

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Partial factor
i. All sites react slower than benzene itself.
The CF3 group is deactivating.
ii. The position that is least deactivated is the CF3
meta position.
4.5 x 10-6 4.5 x 10-6
III. Substituent Effects on Electrophilic
Aromatic Substitution. 67 x 10-6 67 x 10-6
Activating Groups – Electron Donating 4.5 x 10-6
Groups
i. All activating groups are ortho – para
directors.
ii. The more activating the group is, the
milder the conditions need for substitution.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

OH OH
Examples: O2N NO2
i. nitration of phenol HNO3
H2SO4

NO2
To obtain mononitration products
nitric acid, without any added OH OH OH
catalyst must be used. NO2
HNO3
+
ii. Bromination of aniline. NO2
Generally bromination requires the use of
FeBr3 to cause addition to occur. NH2 NH2 NH2
With strongly activating groups like NH2,
the addition occurs without catalyst. Br
Br2
+

Br

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The intermediate is stabilized by the NH2

:NH2
nitrogen atom lone pair of electrons. H H

Br Br

The groups where O

O
this kind of electron .. .. .. .. .. .. ..
donation
important are:
are H2N RHN R2 N HO
.. RO
.. ..OCR NHCR
Deactivating Groups – O O O O
Electron Withdrawing Groups CH , CR ,
Strong electron withdrawing CCl , COH
O
groups are:
COR , NO2 ,
SO3H , C N

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Halogens
Halogens are deactivating groups due to
their electronegativity. .. ..+
They direct ortho – para due to their ability : Cl: :Cl
H
H
to donate a pair of electrons in the same +
manner activating groups do. NO2
NO2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

For example:
Multiple substituent effects. p-Methoxytoluene
When more than one substituent is
All positions are
present on the benzene ring, the directing CH3
activated but the highest
effects of each substituent will function
product yield will come
independently of each other.
from attack at the
To predict sites of reactivity:
positions ortho to the
Represent each substituents directing
methoxy group.
effect with an arrow. OCH3
Strongly activating groups have longer
arrows than weaker activating groups
The two groups are reinforcing so
Deactivating groups have short arrows.
activate the same two positions.
Now place these arrows over the
positions that are activated by each
group.

O2N
OCH3
o-Nitromethoxybenzene
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds
Aryl halides

Aryl halides are compounds containing halogen attached directly

to aromatic ring.
Aryl halides formula was written Ar-X (Ar = aromatic ring; X =
halogen).
Nomenclature of aryl halides:
We describe in the beginning of this course the nomenclature of
different aryl halides

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
Preparation of Aryl Halides
Halogenation of arenes :
electrophilic aromatic H
Br
FeBr3
substitution + Br2 + HBr

diazotization-nucleophilic aromatic substitution

The Sandmeyer reaction:
N
H
N
H
+N Cl
- Cl
NaNO2 CuCl
HCl/H2O Heat
O O + O
+ + N
N N
O- O- O-
1o Aryl Amine Aryl diazonium Aryl chloride
chloride
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

The Schiemann reaction:

N
H H
N +N BF4
- F
NaNO2 H2O
O HCl/H2O O
Heat
O
C BF4 +
C N
CH2CH3 CH2CH3 O-
1o Aryl Amine Aryl diazonium salt Aryl fluoride

diazotization-nucleophilic aromatic substitution

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Reaction of aryl diazonium salts with iodide ion

N
H H - I
N +N Cl Me
Me NaNO2 Me KI
HCl/H2O room
temperature

1o Aryl Amine Aryl diazonium Aryl Iodide

salt

diazotization-nucleophilic aromatic substitution

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Physical properties of aryl halides:

• resemble alkyl halides Cl Cl

• are essentially insoluble in water
• less polar than alkyl halides  2.2 D  1.7 D

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Aryl halides are halides in which the

halogen is attached directly to an
aromatic ring. X
Carbon-halogen bonds in aryl halides are
shorter and stronger than carbon-halogen
bonds in alkyl halides.
X = F, Cl, Br, I

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Reactions of Aryl Halides:

Formation of Grignard reagent:
Br MgBr Cl MgCl
Mg tetrahydro
dry ether furan

Substituted aryl halide with R-, Ar, OR or Cl can be give Grignard reagent.
Other substitution lead to decomposition of Grignard reagent.

Electrophelic Substitution in the ring:

Halogen atom attached to benzene ring make the benzene
ring less reactive than benzene itself, but it directing the se
iterance second group directed to ortho or para.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nitration of halobenzene:
Nitration of halo benzene using nitric acid and sulfuric acid
mixture produced a mixture of ortho and para nitro halobenzene.
X X
X
H2SO4/SO3 SO3H
+
Sulfonation of halobenzene: SO3H
Sulfonation of halo benzene using sulfuric acid-SO3 mixture
(Oleum sulfuric acid) produced a mixture of ortho and para
halobenzene sulfonic acid.
X X
X
HNO3/H2SO4 NO2
+
NO2
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Halogenation of halobenzene:
Introducing another halogen atom to halobenzene performed
using halogen in the presence of FeX3 or AlX3.
X X X
X
X2/FeX3
+
X
Alkylation of halobenzene:
Fridel-Crafts alkylation of halobenzene in the presence of AlX3.
X X
X
RX/AlCl3 R
+
R
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Substitution of halogen atom in halobenzene:

Nucleophilic Aromatic Substitution by Elimination–Addition:
Benzyne
Aryl halides that do not contain an electron-withdrawing group
generally do not react with nucleophiles. Under extreme reaction
conditions, however, nucleophilic aromatic substitution can occur with
aryl halides. For example, heating chlorobenzene with NaOH above
300 °C and 170 atmospheres of pressure affords phenol.

The mechanism proposed to explain this result involves formation of

a benzyne intermediate (C6H4) by elimination–addition. As shown
in Mechanism, benzyne is a highly reactive, unstable intermediate
formed by elimination of HX from an aryl halide.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nucleophilic Aromatic Substitution by Elimination–Addition: Benzyne

Part [1] Elimination of HX to form benzyne:

Cl Cl Elimination of H and X from

-: .. two adjacent carbons forms a
OH ..
H .. - Benzyne
reactive benzyne intermediate
+ + (Steps [1] and
H2O Cl -
Part [2] Nucleophilic addition to
form the substitution product
Addition of the nucleophile (–OH in
-: .. this case) and protonation form the
OH
.. OH OH substitution product (Steps [3] and [4]).
+ OH
-
Benzyne ..
- HOH
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Ullmann Reaction Mechanism

A reaction that is superficially related to the Wurtz-Fitting reaction is the
Ullmann reaction by which diaryl or polyaryl compounds are obtained by
condensing aromatic halides (other than fluorides) with themselves, with
aniline or with sodium phenolates by heating with copper powder or
copper-bronze at an elevated temperature.
The reaction is successful with aryl iodides. However, aryl chlorides and
bromides do not generally undergo this reaction unless an electronegative
group is present in the compound.

I + 2Cu  + 2CuI
Specific example,
Iodo benzene Biphenyl

X + 2Cu  + 2CuI
R R R
Where X is halogen
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

The Wurtz–Fittig reaction is the chemical reaction of aryl halides with alkyl halides
and sodium metal to give substituted aromatic compounds. The reaction is named after
Charles-Adolphe Wurtz, who discovered in 1855 a similar reaction between two alkyl
halides (Wurtz reaction), and Rudolph Fittig, who discovered that also aryl halides
undergo this reaction.
The reaction works best for forming asymmetrical products if the halide reactants are
somehow separate in their relative chemical reactivities. One way to accomplish this is
to form the reactants with halogens of different periods. Typically the alkyl halide is
made more reactive than the aryl halide, increasing the probability that the alkyl
halide will form the organosodium bond first and thus act more effectively as a
nucleophile toward the aryl halide. Typically the reaction is used for the alkylation of
aryl halides; however, with the use of ultrasound the reaction can also be made useful
for the production of biphenyl compounds of type Ph–Ph.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Aromatic nitro compounds:

Aromatic nitro compounds are prepared by direct nitration and was considered as
an example of electrophilic aromatic substitution.
The electrophile is a nitronium ion, 1, which displaces a hydrogen ion from the
benzene ring. It is generated from a Lewis base, nitric acid, in the presence of a
Lewis acid catalyst.
Lewis acid usually used is sulphuric acid; but other Lewis acid can be used glecial
acetic acid or boron trifluoride.

HNO3 + H2SO4 -
H2O + NO2 + HSO4
NO2
+ NO2
+ H

Ar H + HNO3 + BF3 Ar NO2 + H2O + BF3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Dinitrobenzene.

m-Dinitrobenzene:
First nitro group attached with benzene ring lead to deactivation of benzene ring, so
for introducing the second group is too difficult for this reason we are using fuming
nitric acid and conc. sulfuric acid at 95 oC.
NO2 NO2
fuming HNO3
conc. H2SO4
95 oC NO2
o-Dinitrobenzene:
Ortho dinitrobenzene can‘t prepared by direct nitration of benzene.
It prepared from o-nitro aniline by oxidation using caro‘s acid (Peroxymonosulfuric
acid H2SO5), .
NO2 NO2
NH2 H2SO5 NO2
Caro's acid

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

o-Dinitrobenzene:
o-nitro aniline can be oxided by pertrifluoroacetic acid (CF3COOOH)

NO2 NO2
NH2 CF CO H NO2
3 3
methylene
chlorid
p-Dinitrobenzene:
Was synthesized Similar ortho-dinitrobenzene from p-nitroaniline by oxidation either
by pertrifluoroacetic acid (CF3COOOH) or caros acid
NO2 NO2
CF3CO3H
methylene
NH2 chlorid
or NO2
Caro's acid

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
Halonitrobenzene
o-, and p-Halonitrobenzene:
Was synthesized by nitration of halobenzene.

X X
X
HNO3/H2SO4 NO2
+
NO2
Cl Cl Cl
HNO3/H2SO4
NO2
+
NO2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

m-Halonitrobenzene:
Was synthesized by halogenation of nitrobenzene.

NO2 NO2
Cl2/AlCl3

Cl
Nitrotoluene:
Was synthesized by nitration of toluene.

Methylbenzene reacts rather faster than benzene - in nitration, the reaction is about 25
times faster. That means that you would use a lower temperature to prevent more than
one nitro group being substituted - in this case, 30°C rather than 50°C. Apart from
that, the reaction is just the same - using the same nitrating mixture of concentrated
sulphuric and nitric acids.
You get a mixture of mainly two isomers formed: 2-nitromethylbenzene and 4-
nitromethylbenzene. Only about 5% of the product is 3-nitromethylbenzene. Methyl
groups are said to be 2,4-directing.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
For 2-nitromethylbenzene:

CH3 CH3 CH3 CH3

NO2 and for
HNO3 HNO3
4- nitromethyl H2O
+ H2O
benzene
+
NO2

CH3 CH3 CH3

O2N NO2 NO2
HNO3 HNO3

Further nitration for o-,p-

nitrotoluene affording NO2 NO2
2,4,6-trinitrotoluene (TNT)
(TNT):TNT can be oxidized Na2Cr2O 7/H2SO4
by Na2cr2O7/H2SO4 to
give trinitrobwnzoic acid, COOH
O2N O N NO2
which upon heating loss NO2 2
-CO2
CO2 to give trinitrobenzene
NO2 NO2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds OH
OH OH
H2SO4
SO3H
+
SO3H
OH
SO3H

2,4,6-trinitrophenol (picric acid):

Due to the high reactivity of phenol SO3H
and its sensitivity to oxidation with
nitric acid; picric acid can‘t be HNO3
obtained by direct nitration of
phenol. OH
It obtained by sulfonation of phenol, O2N NO2
followed by nitration.

NO2
2,4,6-Trinitrophenol(Picric Acid)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

2,4,6-trinitrophenol (picric acid):

Picric acid also can be prepared from chlorobenzene by nitration followed by
substitution of chlorine by hydroxy group and nitration.

Cl Cl OH OH
O 2N NO2 O2N
HNO3/H2SO4 Na2CO3 NO2
HNO3

NO2 NO2 NO2

Picric acid can be reacted with PCl5 to replace of by hydroxy group with
chlorine, which inturn can be replaced with amino group when treated with
ammonia.
OH Cl NH3
O2N NO2 O2N NO2 O2N NO2
PCl5 NH3

NO2 NO2 NO2

Picryl chloride Picramide

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nucleophelic substitution reactions of nitrobenzene:

Nitro group is m-directing for electrophelic substitution in benzene ring; but in the
case of nucleophilic substitution it was o-,p-directing.

NO2 NO2 NO2

KOH OH
60 oC +
OH
M-dinitro benzene reacted with potassium ferrocyanide in the presence of sodium
hydroxide to introduce hydroxy group in o-position to both two nitro group.

NO2 NO2
K3Fe(CN)6
OH
NaOH
NO2 NO2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Displacment of nitro group in nitrobenzene:

Nitro group is too difficult to undergo displacement but poly nitrobenzene one of these
nitro groups can be displaced by other electrophelic group.

NO2 NO2
NO2 KOH OH
+ KNO2

NO2 NO2
NO2 KOH OC2H5
C2H5OH + KNO2 + H2O

NO2 NO2
NO2 NH3
NH2
+ NH4NO2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Reduction of nitrobenzene:
Nitro group is reduced by catalytic hydrogenation at room temperature and
atmospheric pressure to primary amine.

NO2 NH2
3H2
Pt or
raneyNi
Nitro group also reduced by metal like tin or iron in the presence of HCl to primary
amine.
NO2 NH2
Sn or Fe
HCl

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
O-
CH3OH/Na
N N
Azoxybenzene

Fe H2O2
heat

Azobenzene N N
NaOH/Zn H2/Pt
Nitrobenzene reduction under Air or NaOBr or EtOH/Na
different condition path NaOH/Zn
through several intermediate
NH NH
Hydrzobenzene
compounds. Each one of these NH2
NO2
intermediate compounds gave
Sn or Fe
in the final product aniline.
HCl

Zn/NH4Cl NH OH Sn or Fe
HCl
Phenyl hydroxyl amine
NaCr2O7/H2SO4

Nitrozobenzene
NO

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

If we look to the reduction of NH OH O N

nitrobenzene in alkaline medium we
find it produce phenyl hydroxylamine
and nitrozobenzene.
These two compounds were condensed
with each other to form azoxybenzene
O-
N N
Reduction of azoxybenzene gave hydrazobenzene,
oxidation of hydrazobenzene gave azobenzene.
O-
Reduction
N N NH NH
oxidation

N N
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Benzidine rearrangment:
Hydrazobenzene under acidic condition rearranged to give benzidine.
+
NH NH H
H2N NH2
Mechanism of Benzidine rearrangment:
Protonation of nitrogen atoms of Hydrazobenzene follwed by weakness of N-N bond
and followed by forming bond between two carbons in position 4 acomanied by
breaking bond between two nitrogen and deproaination.

H +
NH +
+ NH2 NH2
2H

NH + +
NH2 NH2
H
+
-2H

H2N NH2
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds
Aryl Amines
Nomenclature of Aromatic Amines

Aromatic amines in the common system they are named by adding suffix amine to the
name of aryl group. They are named as derivatives of the parent member aniline. But in
some cases other names O/m/p - toluidine for o/m/p methylamiline and o/m/p - anisidine
for o/m/p methyl anilines are assigned. Even N-phenyl derivative of aniline is called
diphenyl amine.
NH2 NH2
NH2 NH2

Aromatic amines NO2 OCH3 CH3

classified into 1o, 2o Aniline m-nitro aniline p-anisidine p-toludine
and 3o amines Primary (1o) amins
according to the
CH3
substitution in
NH NH C2H5 NH CH3
nitrogen atom.

Diphenyl amine N-ethyl aniline N-dimethyl aniline

Tertiary (3o) amins
Secondary (2o) amins

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

In the IUPAC system, the simplest aromatic amine is called benzene amine.
Other amines are named as derivatives of benzene amines.

H 3C CH3
NH2 N
NH2
CH3

Benzeneamine 2-Methyl bnzeneamine N,N-Dimethyl bnzeneamine

NH2
Br Br
NH

Br
N-Phenyl bnzeneamine 2,4,6-tribromo bnzeneamine

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
Synthesis of Amines from Nitroarenes
Synthesis of Anilines:
1. Reduction of nitro benzene:
Aniline derivatives are easily prepared by reducing nitrobenzenes with Tin and HCl. The
initial product is the anilinium hydrochloride, which on its treatment with base frees the
aniline.
NO2 NH3 Cl NH2
Sn NaOH
HCl

1. Ammonolysis of activated halobenzene:

When chlorine attached to benzene ring with presence of three nitro groups in o,p
that is make chlorine is easily displaced with amino
Cl NH2
O2N NO2 O2N NO2
NH3

NO2 NO2
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Structure of aromatic amines:

Structure named aromatic amine when the amino group attached to the
directly to the aromatic ring.
In aromatic amine the Amino group attached to the carbon with double
bond. That is like enamine structure

NH2 NH2

C C
C C
NH2 NH
C HC
enamine structure emino structure
stable in aromatic stable in aliphati
system system
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds
Preparation of Aryl Halides
Basicity of aryl amines:
In generally the aromatic amines are less basic than aliphatic amines. If
we compare the methyl amine with aniline, we was found that the pair of
non bonding electrons was located in the nitrogen atom in the case of
methyl amine, while it involved in the ring resonance in case of aniline.
.. +
NH2 NH2
..
H3C NH2
-

Aniline

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Alkylation of aromatic Amines:

Aryl amines resemble the aliphatic amines can be alkylated with alkyl halides.

NH2 +
NH2R X
- NHR

RX NaOH
+ NaX + H2O

Aniline Secondary (2o) amins

Primary (1o) amins

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The alkylation in the presence of excess of alkyl halide don‘t stop

at the formation‘s stage of secondary amines but can be extended
to gave tertiary amines and quaternary ammonium salt
R R
NHR +
NHR2 X
- N

RX NaOH
+ NaX + H2O

Secondary (2o) amins Tertiary (3o) amins

RX

R
R N R X-
+

Quaternary (4o) ammonium

salt
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

It is too difficult the reaction of aryl halide with aryl amine.

Diphenyl amine produced easily from aniline hydrochloride with aniline.
NH2 NH2.HClX

220 oC NH
+ + NH4Cl
Diphenyl amine
Triphenyl amine obtained from other route. From Iodo benzene with
diphenyl amine in the presence of potassium carbonate and copper bronze.

NH K2CO3/Cu N + KI + KHCO3
+
Triphenyl amins

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Acylation of aryl amine:

Primary and secondary amines act as nucleophile and ca be acylated with
acetic anhydride or acyl chloride to produce corresponding amides.
O
NH2
NHCCH3
O O O
+ CH3C O CCH3
+ CH3C OH

O
NH CH3 +
CH3 N-CCH3 HCl.NH CH3
O
+ CH3C Cl
+

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Oxidation of aryl amine:

Primary aromatic are oxidized to several products according to the
reaction condition such as phenyl hydroxylamine, azobenzene, azobenzene.

NH2 PhI/Ac2O
N N

O2N NH2 CF3CO3H O2N NO2

NH2 NaOCl HO NH2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Aniline can be oxidized by sodium hypochlorite to give indoaniline as violet

dye

NH2 NaOCl HO NH2

NaOCl

O NCl H NH2

HO N NH O N NH2

indoaniline
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Nitrosation of amines:

Nitrite ion has interesting properties, when protonated forms nitrous acid.
The produced nitrous acid is in equilibrium with water and nitrosyl cation.

+
O N O + H+ HO N O + H

H
H2O N O HO N O
+

Nitrosyl cation will react with amines in different ways. If the amine is a
secondary amine, the product is an N-nitrosoamine through loss of a proton.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nitrosation of different aromatic amines:

i. Formation of diazonium ions form primary amines:

NH2 N N HSO4
-
NaNO2, H2SO4

H2O at oC

ii. Formation of nitrozylamines form secondary amines:

..
NHCH3 O N N CH3

+ N O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

iii. Tertiary amines; nitrosyl cation adds to tertiary as electrophilic

aromatic substitution reaction at para position to amine group.

N(CH2CH3)2 N(CH2CH3)2

NaNO2, H2SO4
H2O at 0C

NO

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Synthetic application using of aryl Diazonium Salts:

Aryl diazonium ions are synthetically very useful.
They can be used to prepare: phenols, aryl halides, aryl nitriles and hydrogen
insertion.
i. Phenol (hydrolysis of aryl diazonium salt):
Phenols were produced by treating an aryl diazonium salt with water and heat.

NH2 N N HSO4
- OH

NaNO2, H2SO4 H2O, heat

H2O oC

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

ii. Aryl halides:

a. Aryl iodides were prepared by treating a diazonium salt with
potassium iodide.

N N HSO4 - I

KI, RT

b. Aryl fluorides are prepared by treating a diazonium salt with

hydrogentetrafluroborate, HBF4 followed by heat.

N N HSO4- F

1) HBF4
2) heat

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

c. Chlorides or Bromides may be prepared by treating the

diazonium salts with CuCl or CuBr.

Br N N HSO4 - Cl

1) CuBr 1) CuCl
2) heat 2) heat

Diazonium salt reactions involving copper (I) salts are called Sandmeyer

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Reactions..
iii. Aryl nitriles:
Nitriles are prepared by reacting aryl diazonium salts with copper (I) cyanide.

N N HSO4
- CN

CuCN
heat

iv. Hydrogen insertion:

Hypophosphorous acid converts diazonium salts to unsubstituted aryl
derivatives. The reaction is called reductive deamination.

N N HSO4
- H

H3PO2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Azo Coupling Reactions.

Diazonium salts can undergo addition reactions to highly activated
aromatic compounds.
The product is called an azo compound.

N N HSO4 - OCH3

+ N N OCH3

Phenylazo-p-anisole

Azo compounds are generally highly colored and are used as dyes

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

O
NH2 NHCCH3

Ac2O

i. Synthesis of p-bromo-and
p-nitroaniline:
HNO3 Br2
Bromination and nitration of O
O
aniline can‘t be performed NHCCH3
NHCCH3
directely from aniline due to the
sensitivity of amino group to
oxidation. So it must be
protected by acylation before NO2 Br
nitration or bromination. NaOH NaOH

NH2 NH2

NO2 Br

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Condensation of primary NH2 N CHAr

amines with aldehydes:
Primary aromatic amines
ArCHO
condensed with aromatic
aldehydes forming Schiff‘s
base.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
ARENE SULFONIC ACIDS
Introduction:
Benzene sulfonic acid is the simplest sulfonated aromatic compound and is simply a
benzene ring to which is attached a sulfur(VI) as part of an SO3H group. As such, with
three electronegative oxygen atoms, this group is strongly acidic. Needless to say, this
would deplete the aromatic ring of its electron cloud making the molecule highly
deactivated. It is nevertheless 3-directing to any species strong enough to be drawn to
the remaining electron cloud around the aromatic nucleus

The following resonance structures are given not to show that the ring is somehow
furnishing the attached sulfonic acid group with electron density but merely to
indicate the positions most likely to find relative electron density enrichment in what
would otherwise be a generally deficient system vis-a-vis its electron cloud density.
Comparatively speaking then, the 3-positions are slightly electron-density enriched
and any suitable electrophile, seeking electron rich systems, will in all probability
attack the benzenesulfonic acid ring in the 3- and 5- positions.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

OH
O S O-
OH OH +
OH
O S O O S O O S O-
+ +
 -  -
+ OH
+
Benzensulfonic acid O S O-
+

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Using of Sulfuric acid and sulfur trioxide as sulfonating agent to

benzene lead to byproduct diphenylsulfone.

O
O H O
S
S OH + S + H2SO4
+ O O O
O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nomenclature
The nomenclature of aryl sulfonic acid derivatives by naming the compound and
ending by the sulfonic acid
SO3H
SO3H SO3H SO3H
NO2

OH Cl
Benzensulfonic acid 4-hydroxybenzenesulfonic acid 2-nitrobenzenesulfonic acid 3-chlorobenzenesulfonic acid

COOH OH
SO3H

SO3H
2-hydroxycarboxy benzenesulfonic acid 3-hydroxy benzenesulfonic acid
Preparation (2-sulfobenzoic acid)

Both the laboratory as well as the industrial scale preparation of benzenesulfonic

acids is carried out by direct sulfonation of the aromatic ring. This process can be done
using concentrated sulfuric acid but this tends to be slow. Far better to use either
fuming sulfuric acid, ‗oleum‘ (SO3 dissolved in conc. sulfuric acid) or liquid SO3 as the
reaction is then over in a matter of minutes.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Direct sulfonation of benzene

O
+
H O
O Fuming S O
- Rearomatization
S OH
S O
O O H2SO4 O

Two important points need to be mentioned here and these are firstly that the
reactions are easily reversed, quite unlike a lot of other similar chemical
(electrophilic substitution) reactions and secondly that further substitutions are
directed to the 3 and 5 positions as is expected with this substituent.

SO3H SO3H SO3H

Fuming
Fuming
H2SO4
H2SO4
SO3H HO3S SO3H

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Benzenesulfonic acid has a very little uses due to their strong acidity, but its salts are
very important.

Sodium sulfonate when fused with sodium hydroxide gave sodium phenate.

SO3H SO3Na ONa

NaOH NaOH
+ Na2SO3 + H 2O
Fusion

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Properties
Physical Properties
Benzenesulfonic acids are white crystalline solids, very soluble in water giving
strongly acidic solutions that will readily react with metals, carbonates, oxides,
hydroxides and litmus in the expected fashion. (Often deliquescent as the solids they
tend to be stored as the sodium salts).

Sodium salt of benzene sulfonic acid is less soluble in water than free
acid.
For reason it separated as sodium salt by addition of sodium chloride
(salting out) to acid solution.
SO3H SO Na 3

+ NaCl + HCl

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Chemical Properties
A : Reactions involving the SO3H group

a) Replacement of the SO3H with H – formation of parent arene (PhSO3H --> PhH )
Hydrolysis of the benzenesulfonic acids with dilute HCl at 150oC, under pressure,
yields the parent arene (- not the phenol!)
SO3H
dil. HCl/150 oC
+ H2O
Pressure

The hydrolysis is the exact reverse reaction of the sulfonation process.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
b. Replacement of SO3H with OH --formation of phenols (PhSO3H --> PhOH)
Fusion of the sulfonic acids with sodium hydroxide initially gives the phenate salt
with the phenol being released by the subsequent addition of mineral acid.
SO3H ONa OH
NaOH HCl
fuses + Na2SO3

c.Substitution of SO3H with CN -- formation of benzonitrile (PhSO3H --> PhCN)

An important reaction that easily gives us a small carbon chain extension (which may
be very significant in some reaction sequences!) is that where sodium cyanide is heated
with sodium benzenesulfonate, easily prepared from the sulfonic acid by
neutralization. (The toxic gas HCN can easily be released if the sulfonic acid is treated
directly with NaCN)
SO3H SO3Na CN

NaOH NaCN
+ Na2SO3
fuses
(This reaction is of some importance because the substitution of Ar-Cl by CN is
not possible, quite unlike the aliphatic halogenated compounds!)
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Formation of Arenesulfonyl chloride, an acid chloride (PhSO3H--> PhSO2Cl)

The OH group found on the SO3H group can be replaced by a Cl in the same way that it
is for the carbon analogues. Treating the sulfonic acids with PCl5 affords the sulfonyl
chlorides :

SO3H SO2Cl
PCl5

benzenesulfonyl chloride

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

As acid chlorides, they give the same reactions seen with the carbonyl species
except that they do not react with the same vigour, but will nevertheless give
esters and amides, the sulfonate esters and sulfonamides respectively. (Reaction
of the sulfonyl chloride with water is slow, unlike the carbon equivalent and it
is for this reason that formation of esters can be brought about in aqueous
conditions)
SO2Cl SO OR
2

+ ROH + HCl

SO2Cl SO2NHR

+ RNH2 + HCl

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

B : Reactions on the ring

The ring is deactivated and the sulfonic acid group is 3-directing to electrophiles. With
the exception of the Friedel-Crafts alkylations, which will not work on account of the
ring being too deactivated, the electrophiles give 3-substituted sulfonic acids when
harsher conditions than those needed for benzene are used.
e.g. Nitration
Nitration of benzenesulfonic acid yields the 3-nitrobenzenesulfonic acid, as expected :

SO3H SO3H
SO3H
HNO3
HNO3
H2SO4
H2SO4 heat O2N NO2
heat NO2
3-nitrobenzenesulfonic 3,5-dinitrobenzenesulfonic
acid acid

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Bromination
Bromination of benzenesulfonic acid in the presence of iron yields the 3-
bromobenzenesulfonic acid, as expected :

SO3H
SO3H
Fe
+ Br2 + HBr
Br
3-Bromobenzenesulfonic
acid
Bromination of 2,5-
dimethyl benzenesulfonic CH3
CH3
acid in the presence of SO3H
water lead to bromination OH
Br2
accompanied by + H2SO4 + HBr
substitution of sulfonic H2O
CH3 Br Br
group with hydroxyl group.
CH3
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Also nitration of 2-Chloro benzenesulfonic acid in the presence of water lead

to nitration accompanied by substitution of sulfonic group with hydroxyl
group.

Cl
Cl
SO3H
HNO3 OH
H2O + H2SO4 + HBr
O2N NO2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Uses of arenenesulfonic acid and their salts:

Chloramine T:

CH3

SO2N Cl Na

Chloramine T sodium salt

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Toluene sulfonamide was prepared either:

a. from toluenesulfonic acid followed by converting it to the coeesponding
acid chloride and after that reacting it with ammonia.
b. From toluene by reacting with chlorosulfonic acid to give
toluenesulfonyl chloride and the reacting with ammonia.
CH3
CH3 CH3
H2SO4
SO3H
+

SO3H
PCl5
PCl5

CH3 CH3 CH3

ClSO2SOH SO2Cl
-H2O

SO2Cl
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Chloramine-T is prepared from p-toluenesulfonamide and

sodium hypochlorite, with the latter being produced in situ
from sodium hydroxide and chlorine (Cl2). Further
chlorination gave dihloramine T.

CH3 CH3
CH3 CH3
NaOCl
NH3
NaOCl

SO2N Cl Na SO2N Cl
SO2Cl SO2NH2 Cl
Chloramine T sodium salt Dichloramine T

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Saccharin can be produced in various ways. The original route by Remsen

and Fahlberg starts with toluene; another route begins with o-
chlorotoluene. Sulfonation of toluene by chlorosulfonic acid gives the ortho
and para substituted sulfonyl chlorides. The ortho isomer is separated and
converted to the sulfonamide with ammonia. Oxidation of the methyl
substituent gives the carboxylic acid, which cyclicizes to give saccharin free
acid:
CH3
CH3 NH
SO2Cl O
SO2NH2 S
NH3
Oxidation O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Phenols
Topics Covered:
1. Phenol - Bonding, Physical Properties and Reactions

2. Electrophilic Aromatic Substitution: Halogen, Nitration, Nitrosation

3. O- and C-Acylation of Phenols: Fries Rearrangement

4. Kolbe-Schmitt Reaction: Carboxylation of Phenols

5. Preparation and Cleavage of Aryl Alkyl Ethers

6. Claisen Rearrangement of Aryl Allyl Ether

7. Preparation of Quinones

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nomenclature of Phenols

named on basis of phenol as parent substituent's listed in alphabetical order

lowest numerical sequence: first point of difference rule

OH
CH3

Cl
5-chloro-2-methylphenol

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

OH
OH OH
OH

OH OH

1,2-Benzenediol 1,3-Benzenediol 1,4-Benzenediol

(common name: (common name: (common name:

pyrocatechol) resorcinol) hydroquinone)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

OH

p-Hydroxybenzoic acid
COOH

name on basis of benzoic acid as parent

higher oxidation states of carbon outrank

hydroxyl group

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Epinephrine
is the principal hormone governing the "fight or
flight" response. This hormone also triggers a OH O
variety of physiological events, including increased
heart rate. It is biosynthesized from from the amino OH
acid tyrosine by way of DOPA. NH2
The importance of dopamine in neural transmission is Tyrosine
emphasized by the number of major neurological diseases that
are associated with improper dopamine regulation. The
earliest indication of this type of defect was the finding that H
dopamine levels are abnormally low in a particular region of HO N
the brain of patients with Parkinsonism, a severe neurological H
disorder. Attempts to treat such patients with dopamine were Dopamine
futile, because after injection, dopamine does not cross the HO
blood brain barrier. However, the dopamine precursor, dopa,
does cross the blood brain barrier. For many individuals with
Parkinsonism, daily doses of dopa have provided dramatic OH H
clinical improvement. HO N
Dopamine is a catecholamine derived from tyrosine. Other H
catecholamines include epinephrine and norepinephrine. Epinephrine
HO
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Epinephrine, also known as adrenaline, is the principal hormone governing

the "fight or flight" response to various stimuli. In addition to stimulating
glycogenolysis, the hormone triggers a variety of physiological events, such as
increasing depth and frequency of heartbeats.

Epinephrine is secreted from the adrenal medulla and binds to specific

receptors on muscle cell membranes. Binding of the hormone at the
membrane stimulates the synthesis of cAMP by membrane-bound adenylate
cyclase, through the action of a G protein, Gs. cAMP in turn activates cAMP-
dependent protein kinase, which catalyzes the phosphorylation of
phosphorylase b kinase. This kinase in turn catalyzes the phosphorylation of
phosphorylase b to a and, hence, the activation of glycogen breakdown,
through the action of phosphorylase a. These events explain how the secretion
of relatively few molecules of hormone, such as epinephrine, can, within just a
few moments, trigger a massive conversion of glycogen to glucose-1-
phosphate.
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Phenol is highly corrosive and moderately toxic. It effects humans by burning the
skin and other tissue that it comes into contact with. This gives severe skin burning
and if inhaled serious internal corrosion. The skin burning is not initially felt
because the phenol has a local anesthetic effect. It can affect the central nervous
system, which will at first lead to sweating, weakness, dizziness and twitching but
with prolonged exposure leads to nausea, vomiting and coma. If ingested even a
small dose can lead to be fatal in humans and therefore care must be taken at all
times using phenol-containing products.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

OH

phenol is planar
C—O bond distance is 136 pm, which is
slightly shorter than that of CH3OH (142 pm)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Physical properties

Hydrogen Bonding in Phenol

The hydroxyl group of

phenols allows hydrogen
bonding to other phenol
molecules and to water.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Compared to compounds of similar size and molecular weight, hydrogen bonding in

phenol raises its melting point, boiling point, and solubility in water.

C6H5CH3 C6H5OH C6H5F C6H7N

Molecular weight 92 94 96 93

Melting point (°C –95 43 –41 −6.3

Boiling 111 132 85 184

point (°C,1 atm)
Solubility in 0.05 8.2 0.2 3.6 g/100 mL at
H2O (g/100 20 °C
mL,25°C)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Phenols

Methods of phenol preparation:

Industrially phenol and its derivatives were separated from the coal tar during
formation of cock coal .

Practically phenols prepared from the corresponding sulfonic acid by fusion with
sodium hydroxide.
SO3H ONa OH
NaOH HCl
fuses + Na2SO3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Also phenol was prepared from the corresponding diazonium salt by heating its
aqueous solution. NH N N HSO
- OH
2 4

NaNO2, H2SO4 H2O, heat

H2O oC

Nitro phenols was prepared Cl OH

from the corresponding
halonitrobenzene by heating NaOHaq.
with sodium hydroxide
solution. NO2 NO2

Cl OH
O2N NO2
Na2CO3aq. Dinitro phenols was prepared
from the corresponding
NO2 NO2 halodinitrobenzene by heating
with sodium carbonate solution.
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

OH
Phenol can be prepared from OH
COOH
the corresponding hydroxy NaOH/CaO2
carboxylic acid by
-CO2
decarbxylation.

Phenol can be prepared from

the corresponding Grignard
reagent.
Cl MgCl OMgCl OH
Mg O H2O
dry ether + MgClOH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Phenols
Aromatic rings with an OH group are named as phenols.

OH OH OH
Cl

NO2
Cl
phenol m-nitrophenol 2,4-dichlorophenol

Naphthalene rings with an OH group are named as naphthols.

OH
HO

-naphthol -naphthol
1-napthol 1-napthol

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Dihydroxy phenols:
The three possible diphenols all have common names. They are systematically
named as benzenediols.
OH OH OH
OH

OH
OH
1,2-benzenediol 1,3-benzenediol 1,4-benzenediol
pyrocatechol resorcinol hydroquinone
Triphenols: OH
OH
HO OH

HO OH

1,3,5-Benzenetriol 1,2,3-Benzenetriol
(Fluoroglcinol) (Pyrogalol)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Higher order substituents.

If a higher order substituent is present, the OH group is named as a hydroxyl
group.

OH

C
O OH
p-hydroxybenzoic acide

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Properties of Phenols
Structure of phenol.
The oxygen in phenols is sp2 hybridized.
This permits interaction of the lone-pair of electrons on oxygen with the π system of
the ring.

Physical Properties.
i. Hydrogen bonding. OH O
Phenols can be hydrogen bonded to themselves or to +
other oxygen containing molecules. H
The hydrogen bonding has the effect of increasing the
melting point, boiling point and water solubility of
O O
phenols compared to other aromatics of similar molecular
weight.
ii. Acidity of Phenols.
Typical alcohol acidities lie in the range of pKa = 14 – 17.
The acidity of phenols lie in the range of pka = 6 – 12. pKa = 10

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The increased acidity of phenols compared to alcohols is due to resonance

stabilization of the anion in the phenol.
Substituent effects on the acidity of phenols
Electron releasing groups have very little effect on the acidity of phenols.
OH OH OH

CH3 OCH3
pKa 10 10.3 10.2

OH OH OH
Electron-withdrawing
groups increase acidity

Cl NO2
pKa 10 9.2 7.2
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

The effect of the electron-withdrawing groups is most pronounced in the ortho

and para positions.
OH
OH OH
NO2

NO2
NO2
pKa 7.2 8.4 7.2

Effects are cumulative.

OH OH
OH
O2N NO2
NO2 NO2

NO2 NO2
pKa 7.2 4.0 0.4

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The reason for these effects is the resonance stabilization of the negative charge
in the anion.

O O O O

N O N O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Synthesis of phenols
Phenols can be obtained as described before from aryl
diazonium ions. Diazonium salts react with water and heat
to form phenols.
NH2 N N HSO4- OH

NaNO2, H2SO4 H2O, heat

H2O at 0 C

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Reactions of Phenols
Electrophilic aromatic substitution in phenols
Phenol is one of the strongest activating groups available for electrophilic aromatic
substitution.
Because of this, the substitution of phenols generally require slightly different
conditions than other substitutions.
The reactions must be ―toned down‖ to prevent multiple substitutions from
occurring.
i. Halogenation
Bromination using Br2/FeBr3 of phenol leads directly to 2,4,6-tribromophenol.

OH OH
Br Br
FeBr3
+ Br2

Br

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

To affect monobromination, bromine alone in a nonpolar solvent is used.

OH
OH

ClCH2CH2Cl
+ Br2

Br

Even Use of a polar solvent leads to multiple halogenation.

OH OH
Br
H2O
+ Br2

Br

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

ii. Nitration.
Again this need to ―tone down‖ the reagent.
The use of nitric acid in acetic acid at low temperature afforded mononitrated
derivative.
If multiple substituents are present the OH group will determine the
regioselectivity.
OH OH
NO2
Acetic Acid
+ HNO3

CH3 CH3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
Nitrosation
Nitrosation of aromatic rings rarely
occurs.
Only very highly activated aromatic OH OH
rings will undergo reaction with nitrosyl
cation. H2SO4
The hydroxyl group is activating enough + NaNO2
to cause the reaction to take place.

Nitrosation of aromatic rings rarely occurs. NO

Only very highly activated aromatic rings will undergo reaction with nitrosyl cation. The
hydroxyl group is activating enough to cause the reaction to take place.
When phenol heated with sodium nitrite in the presence of sulfuric acid the p-
nitrosophenol, whch can be reacted with another molecule of phenol, this reaction called
Libermann reaction.
OH OH

OH
H2SO4 HO N O
NaNO2

NO

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Sulfonation:
Through hydroxyl activation, sulfonation can be performed by using sulfuric acid
alone.
OH OH
H2SO4

SO H
3
Friedel-Crafts Alkylation:
Aluminum chloride is the traditional catalyst used for Friedel-Crafts alkylation.
Weaker catalysts than AlCl3 can be used with phenols.
Usually when phenol is alkylated alcohols with an acid such as phosphoric or sulfuric
is used.
OH OH

(CH3)3COH
H3PO4

C(CH3)3
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

The alkylating agents for phenols not alkyl halide but may be alcohol or olefins.

OH OH OH
H2SO4 CHR2
+ R2CHOH +

CHR2

Condensation with aldehydes:

OH OH OH
dil. NaOH CH2OH
+ HCHO +

CH2OH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Formaldehyde reaction with phenol was controlled but may be condensed further to
give Phenol-Formaldehyde Resins this called Lederer Manasse reaction. This reaction
was considered a type of aldol condensation.

OH OH OH OH
CH2OH H
dil. NaOH
+
dil. NaOH
HCHO

OH OH OH
OH
HOCH2 CH2OH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Mannich Reaction:
Mannich Reaction usually between formaldehyde, secondary amine. In the case of
phenol the reaction occurred between formaldehyde, secondary amine and phenol to
give Mannich base.
OH OH OH
HCHO
CH2OH HN(CH3)2
+
HN(CH3)2
CH2OH
HN(CH3)2

OH
(CH3)2NH2C CH2N(CH3)2 OH OH
HCHO
CH2N(CH3)2
HN(CH3)2 +
CH2N(CH3)2
CH2N(CH3)2
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Condensation with aldehydes:

Condensation of phenol with aldehydes in acid medium two mols of aldehyde

condensed with mole of phenol as follwes:
OH
OH

H2SO4 in AcOH
or ZnCl2 + HCl CHR
H
O CHR
H
OH

OH
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds
O
Friedel-Crafts Acylation: OH OCCH3
In the presence of AlCl3, phenols O
are acylated to give hydroxyl
+ CH3CCl
ketones.
On the other hand esters will be
formed in the absence of OH OH
O
catalyst. AlCl3
+ CH3CCl

CCH3
Preparation of Aryl Ethers: O
Aryl ethers are generally prepared by using a Williamson
Synthesis.
In this reaction, phenol must function as the nucleophile.

-+
O Na + R X O R + NaX

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

An alkoxide will not react with most aryl halides.

O- Na
+ X
R + No Reaction

Examples
- +
O Na + CH3CH2CH2Br O CH2CH2CH3

K2CO3
OH + H2C CH CH2Br O CH2CH CH2

Nitroaryl halides will react with an alkoxide ion provided the nitro group is ortho
or para to the halogen.
Cl OCH3

CH3O Na
- +

NO2 NO2
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Aryl alkyl ethers cleave to produce an alkyl halide and a phenol.

Examples
OH

OCH2CH3 HBr CH3CH2Br

OCH3 OH
HBr CH3Br
OH OH

viii. Claisen Rearrangement of Allyl Aryl Ethers

Allyl Aryl ethers undergo rearrangement when heated leads to alkyl phenol.

O CH2CH CH2 OH
200ºC

CH2CH CH2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

O O
CH2
CH2
CH
CH CH2
H 2C H

OH

CH2CH CH2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The Claisen rearrangement is called a sigmatropic rearrangement.

A sigma bond rearranges from one end of a conjugated system to the other end.
The allyl system is a conjugated system.
In the ether the sigma bond is attached to the oxygen and the allyl group.
In the phenol the sigma bond is attached the the aryl carbon and the opposite end of
the allyl group.

ix. Formylation:
When phenols heated with chloroform in the presence of KOH, hydroxyl aromatic
aldehydes were produced this reaction called Reimer-Tiemann
formylation
OH OH OH
CHO
CHCl3
3KOH + + 3KCl + 2H2O

CHO

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Carboxylation:
Sodium Phenolate reacts with CO2 at 125 and at high pressure to afford salicylic
acid, this reaction called Kolbe-Schmitt Reaction.

-O Na+ OH
OH
CO2Na
CO2H
125 oC/7 atm. +
+ 2
CO H

. Oxidation of Phenols.
A quinone is a cyclohexadienedione. O O
O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

1,4-benzenediols are readily oxidized to quinones

OH O

+ Na2Cr2O7/H2SO4

OH O
OH p-benzoquinone
O
OH
O
+ Ag2O
CH3
CH3
4- Methyl-1,2-benzoquinone

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

1,4-benzenediols are readily oxidized to quinones.

OH O

+ Na2Cr2O7/H2SO4

OH O
p-benzoquinone

OH O
OH O
+ Ag2O

CH3 CH3
4- Methyl-1,2-benzoquinone

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nitrozation:
Phenol react with nitrous acid to give p-nitrosophenol.
The produced nitrosophenol was in tautomer with p-benzoquinone monoxime
OH

HO H + HO NO
NO
O O
O H

NO NOH
NO
enol form keto form p-benzoquinone monoxime

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

If nitrozation carried out in the presence of conc. Sulfuric acid further condensation
of other phenol molecule to give dark blue dye called phenolindophenol sulphate salt
which when diluted with water liberate phenolindophenol as red color which when
treated with sodium hydroxide return to blue color to give sodium salt.
This reaction called Liebermann reaction.

O NOH + H OH HO
+
N OH HSO4
-
Deep Blue
Phenolindophenol sulphate salt

H2O

O N O Na
- + NaOH
O N OH
Deep Blue Deep Red
Phenolindophenol sudium salt Phenolindophenol

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Aromatic aldehydes and Ketones

Aromatic aldehyde containing aldyhedic group (-CHO) attached directly to the

aromatic ring
CHO
CHO OH
CHO

NO2
benzaldehyde 2-hydroxybenzaldehyde 4-nitrobenzaldehyde
or comon name (salicaldehyde) or p-nitrobenzaldehyde

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Synthesis of aromatic aldehydes

Methyl side chain oxidation:
Methyl side chain was oxidized with MnO in the presence of
sulfuric acid lead to the formation of benzaldehyde which
oxidized in the reaction medium to benzoic acid.
To prevent the further oxidation the reaction was carried in the
presence of acetic anhydride which gave benzal diacetal whuch
hydrolyzed with water to benzaldehyde.

CH3 CHO
2 MnO2
H2SO4 + 3H2O + 2MnSO4

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

CH3 CHO CO2H

2 MnO2
H2SO4
+
3H2O + 2MnSO4
2 MnO2
H2SO4 CH(OCCH3)2 CHO
H2O
(CH3CO)2O + 2CH3COOH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

From hydroxymethyl side chain oxidation:

CH2 OH CHO
N-Chloro-
Succinimide

From unsaturated side chain oxidation:

CH CHCH3 CHO
KMnO4
+ CH3COOH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Hydrolysis of benzal dihalide:

OH
CHCl2 CH OH
CHO
NaOH aq. -H2O
or Ca(OH)2

Gattermann-Koch reaction:
CH3 CH3
CO + HCl or AlCl3/CuCl
+ HCl
HCOCl
CHO

HCOO H + Cl SO3H HCl + CO + H2SO4

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Gattermann hydrogen cyanide reaction:

OH OH OH
HCN/HCl/ZnCl2 H2O
+ NH4Cl
OH OH OH
ClCH=NH CH NH CHO
Reimeri Tiemann reaction:

OH OH
H Cl
NaOH CHCl2
+ H C Cl + EtOH
Cl
H2O

OH OH
HC OH
CHO
OH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Reactions of Aromatic aldehydes:

You are study the carbonyl compounds reactions in the 1st

term. The reactions of aldehydes are mainly nucleophilic
addition reactions such as:
Oxime formation
Acetal and hemiacetal formation
Schif‘s base formation

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Oxidaion of Aromatic aldehydes:

benzaldehydes were oxidized with potassium permanganate in

acidic medium and basic medium to afford benzoic acid.
CHO + COOH
KMnO4/H

CHO -
KMnO4/OH
COOH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Halogenaion of Aromatic aldehydes:

Benzaldehyde was reacted with chlorine in absence of catalyst,
while substitution of aldhydic group hydrogen to give benzoyl
chloride
CHO COCl
Cl2
+ HCl

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Cannizaro reaction:

Due to absence of -hydrogen in the aromatic aldehydes. The

reaction with sodium hydroxide undergo Cannizaro reaction
and doesn‘t gave aldol condensation.

If we look to the mechanism it will be seen as two molecule of

aldehyde one oxidized and the other one reduced.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Crossed-Cannizaro reaction:

When benzaldehyde heated with concentrated sodium

hydroxide in the presence of formaldehyde. Cannizaro reaction
occurred between molecule of benzaldehyde and molecule of
formaldehyde. Due to easily oxidation of formaldehyde than of
benzaldehyde it oxidized to formic acid and benzaldehyde
reduced to benzyl alcohol.

CHO CH2OH
NaOH
+ HCHO + HCOONa

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

BENZOIN CONDENSATION

The Benzoin Condensation is a coupling reaction between two aldehydes that allows
the preparation of α‐hydroxyketones. The first methods were only suitable for the
conversion of aromatic aldehydes.

O
O
H -
CN
H2O/EtOH
OH
Benzoin

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Mechanism of Benzoin Condensation :

Addition of the cyanide ion to create a cyanohydrin effects an umpolung of the
normal carbonyl charge affinity, and the electrophilic aldehyde carbon becomes
nucleophilic after deprotonation: A thiazolium salt may also be used as the catalyst
in this reaction .

A strong base is now able to deprotonate at the former carbonyl C‐atom:

A second equivalent of aldehyde reacts with this

carbanion; elimination of the catalyst regenerates the
carbonyl compound at the end of the reaction:

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

OH
O O-
H O H CN
H CN- CN
- H
H -OH
H2O -OH
-
OH
H O CN OH
OH
H CN
H - CN

OH H
-O
H O H O
-
O CN
H O
H

OH
OH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Aldol Condensation

Aldol reactions join two carbonyl containing molecules together forming a new
carbon-carbon bond between the alpha carbon of one molecule and the carbon of the
carbonyl of the second molecule. This forms a beta hydroxyl carbonyl compound. If
this product undergoes a subsequent dehydration, then an aldol condensation
reaction has taken place.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The reaction that is being carried out today combines two equivalents of benzaldehyde
with one equivalent of acetone in the presence of a base to form the product 1,5-
diphenyl-1,4-pentdiene-3-one. The common name of this material is dibenzylactone.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Aromatic Carboxylic acid

Carboxylic acid whereas the carboxylic group attached directely to the aromatic ring.
COOH

R
General Methods of preparation of carboxylic acid:
Oxidaion of Aromatic aldehydes:

benzaldehydes were oxidized with potassium permanganate in

acidic medium and basic medium to afford benzoic acid.
CHO
-
KMnO4/OH
COOH
+ CHO
KMnO4/H

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Hydrolysis of aromatic nitriles:

C N COOH
H2O/H2SO4

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Carobnylation of Grignard reagent:

OMgBr
COOMgBr
CO2 COOH
H2O

Fridel Craft :
Benzene with oxalyl chloride in the presence of alimnium
chloride affording benzoic acid.
COCl COOH
COCl H 2O
+ + AlCl3
COCl

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

From phthalic anhydride:

Phthalic anhydride on the presence of metalic catalyst and
steam affording benzoic acid.
O
COOH
O + H 2O
ZnCl2
O
From benzotrichloride:
CH3 CCl3
Cl2 COOH
H2O
h
Ca(OH)2

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Properties of Aromatic Carboxylic acid:

Acidity of Aromatic carboxylic acid:

Acidity of aromatic carboxylic acid is less than the

corresponding aliphatic acid.
Acidity of aromatic carboxylic acid increased with the presence
of electron withdrawing groups and decreased with presence
electrons donating groups

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Oxalic (1) H2C2O4 HC2O4- 5.9 x 10-2 1.23

Formic HCOOH HCOO- 1.77 x 10-4 3.75

Acetic CH3COOH CH3COO- 1.76 x 10-5 4.75

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Chemical Properties of Aromatic Carboxylic acid:

Esterification:
Aromatic acid condensed with alcohols in dehydrating agent
like sulfuric acid to give ester.
COOH H OC2H5 COOC2H5
H2SO4
-H2O
Ethyl benzoate
Formation of acid chloride:
Aromatic acid reacted with chlorinating agents like PCl5 or
SOCl2 give acid chloride.
COOH COCl
PCl5 or
SOCl2
benzoyl chloride
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Reduction of aromatic acid:

Aromatic acids and its esters or acid chloride were reduced with
LiAlH4 to give primary alcohol
COOH CH2OH
LiAlH4

benzyl Alcohol
Decarboxylation of aromatic acid:
Aromatic acids when heated with soda lime loss carbon dioxide
to give benzene and its derivatives
COOH
CaO
-CO2
benzene

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Chemical Properties of Aromatic Carboxylic acid:

Reactions on aromatic ring:
Nitration:
COOH
COOH
HNO3 H2SO4
+
NO2
m-nitrobenzoic

Sulfonation:
COOH COOH
+ conc. H2SO4
SO3H
m-sulfobenzoic acid
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

Halogenation:

COOH
COOH
+ Cl2 FeCl3
Cl
m-Chlorobenzoic acid

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Hydroxy carboxylic aromatic acid:

There are three isomers of benzene dicarboxylic acid
COOH

OH
o-nitrobenzoic
Salicylic Acid

Synthesis of salycilllic acid:

By colb-shmidt reaction
OH ONa ONa
NOH COOH
CO2
heat/7atm.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Synthesis of salycilllic acid:

From anthranilic acid diazonium salt
COOH
COOH COOH
NaNO2 H2O
NH2 HCl
N Cl -
+ Heat
N OH

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Proparties of salycilllic acid:

When heated with soda lime loss CO2 to give phenol

COOH OH
CaO
Heat
OH
Reacted with Methanol to give methyl salicylate

COOH
CH3OH
COOCH3

OH H2SO4
OH
methyl salicylate

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Reacted with Acetyl chloride or acetic anhydride to give

acetyl salicylic (Aspirin).

COOH
CH3COCl
COOH

OH or Ac2O
Asprin
OCOCH3

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Dicarboxylic aromatic acid:

There are three isomers of benzene dicarboxylic acid
COOH
COOH COOH

COOH
COOH COOH
Phthalic acid
Isophthalic acid Terphthalic acid
Synthesis of phthalic acid:
By oxidation of ortho-dialkyl benzene
CH3 COOH
KMnO4
CH3 COOH
ortho-xylene Phthalic acid
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

From phthalic anhydride:

Commercially phthalic acid was obtained from phthalic
anhydride, which produced from naphthalene oxidation

HgSO4
H2SO4 O
Naphthalene COONa
NaOHaq
O
COONa
V2O5 O disodium phthalate
O2
HCl
Naphthalene
COOH

COOHa
Prof. Dr. Adel M. Kamal El-Dean
Phthalic acid
Aromatic compounds

Reactions of phthalic acid and phthalic anhydride:

phthalic acid and phthalic anhydride condensed with
phenol in sulfuric acid to give phenolphthalein
OH OH

HO OH
H O H
COOH
H2SO4
O Ocolorless

phenolphthalene
COOH
O O
NOH
NaO O

ONa
Pink O
Prof. Dr. Adel M. Kamal El-Dean
Aromatic compounds

phthalic acid and phthalic anhydride condensed with

resorcinol in sulfuric acid to give fluoresscein
HO OH HO OH
HO O OH
H OH
H2SO4
O O

O O

NaO O O

Green Fluorescence colorless

ONa
O

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds
ARENE SULFONIC ACIDS
Introduction:
Benzenesulfonic acid is the simplest sulfonated aromatic compound and is simply a
benzene ring to which is attached a sulfur(VI) as part of an SO3H group. As such, with
three electronegative oxygen atoms, this group is strongly acidic. Needless to say, this
would deplete the aromatic ring of its electron cloud making the molecule highly
deactivated. It is nevertheless 3-directing to any species strong enough to be drawn to
the remaining electron cloud around the aromatic nucleus

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

The above resonance structures are given not to show that the ring is somehow
furnishing the attached sulfonic acid group with electron density but merely to
indicate the positions most likely to find relative electron density enrichment in what
would otherwise be a generally deficient system vis-a-vis its electron cloud density.
Comparatively speaking then, the 3-positions are slightly electron-density enriched
and any suitable electrophile, seeking electron rich systems, will in all probability
attack the benzenesulfonic acid ring in the 3- and 5- positions.

Preparation
Both the laboratory as well as the industrial scale preparation of benzenesulfonic
acids is carried out by direct sulfonation of the aromatic ring. This process can be done
using concentrated sulfuric acid but this tends to be slow. Far better to use either
fuming sulfuric acid, ‗oleum‘ (SO3 dissolved in conc. sulfuric acid) or liquid SO3 as the
reaction is then over in a matter of minutes.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Direct sulfonation of benzene

Two important points need to be mentioned here and these are firstly that the
reactions are easily reversed, quite unlike a lot of other similar chemical
(electrophilic substitution) reactions and secondly that further substitutions are
directed to the 3 and 5 positions as is expected with this substituent.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Nomenclature
This functionality is the highest ranking functionality we come across and hence
the compounds bearing this functionality are all derivatives of the arenesulfonic acid,
benzenesulfonic acid in our case.

Properties
Physical Properties
Benzenesulfonic acids are white crystalline solids, very soluble in water giving
strongly acidic solutions that will readily react with metals, carbonates, oxides,
hydroxides and litmus in the expected fashion. (Often deliquescent as the solids they
tend to be stored as the sodium salts)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Chemical Properties
A : Reactions involving the SO3H group

a) Replacement of the SO3H with H – formation of parent arene (PhSO3H --> PhH )
Hydrolysis of the benzenesulfonic acids with dilute HCl at 150oC, under pressure,
yields the parent arene (- not the phenol!)

The hydrolysis is the exact reverse reaction of the sulfonation process.

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

b. Replacement of SO3H with OH --formation of phenols (PhSO3H --> PhOH)

Fusion of the sulfonic acids with sodium hydroxide initially gives the phenate salt
with the phenol being released by the subsequent addition of mineral acid.

c.Substitution of SO3H with CN -- formation of benzonitrile (PhSO3H --> PhCN)

An important reaction that easily gives us a small carbon chain extension (which may
be very significant in some reaction sequences!) is that where sodium cyanide is heated
with sodium benzenesulfonate, easily prepared from the sulfonic acid by
neutralization. (The toxic gas HCN can easily be released if the sulfonic acid is treated
directly with NaCN)

(This reaction is of some importance because the substitution of Ar-Cl by CN is

not possible, quite unlike the aliphatic halogenated compounds!)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Formation of Arenesulfonyl chloride, an acid chloride (PhSO3H--> PhSO2Cl)

The OH group found on the SO3H group can be replaced by a Cl in the same way that it
is for the carbon analogues. Treating the sulfonic acids with PCl5 affords the sulfonyl
chlorides :

As acid chlorides, they give the same reactions seen with the carbonyl species except
that they do not react with the same vigour, but will nevertheless give esters and amides,
the sulfonate esters and sulfonamides respectively. (Reaction of the sulfonyl chloride
with water is slow, unlike the carbon equivalent and it is for this reason that formation
of esters can be brought about in aqueous conditions)

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

B: Reactions on the ring

The ring is deactivated and the sulfonic acid group is 3-directing to electrophiles. With
the exception of the Friedel-Crafts alkylations, which will not work on account of the
ring being too deactivated, the electrophiles give 3-substituted sulfonic acids when
harsher conditions than those needed for benzene are used.

e.g. Nitration
Nitration of benzenesulfonic acid yields the 3-nitrobenzenesulfonic acid, as expected :

etc

Prof. Dr. Adel M. Kamal El-Dean

Aromatic compounds

Aromatic Nitro compounds

Aromatic Nitro compounds were prepared by direct nitration using:

1. Concentrated nitric acid
2. Fuming nitric acid(containing 6-12% NO2 gas.
3. Mixed acids(Concentrated nitric acid : Concentrated sulfuric acid)
4. Concentrated nitric acid : BF3

E- Nitration
1- Benzene can be treated with a nitric acid to
give nitrobenzene.
2- Overall reaction
Prof. Dr. Adel M. Kamal El-Dean