PharmD Program

Fall 2023
Pharmaceutical Organic
Chemistry-I
PC 102
Prof. Dr. Ehab Gedawy
 Lecture 6
✓ Aromaticity
✓ Nomenclature of aromatic
compounds
 Advised references;

1- Organic Chemistry;
11th edition,
Graham Solomons; Craig Fryhle; Scott Snyder.

2. L.G. Wade, J. W. Simek “Organic Chemistry” Pearson, 9th

Edition (2016).

3. John E. McMurry “Organic Chemistry”, Cengage Learning,

9th Edition, (2015).
 Office Hours
• Sunday: 11-1 pm
• Monday: 12-02 pm
• Location: level 3
quality assurance unit
 Learning outcomes covered by the lecture

1-1-1.2- Apply fundamental rules of IUPAC system to predict nomenclature of

different organic compounds.

1-1-1.3- Explain the concept and requirements of aromaticity and the structure of
benzene and utilizing Huckle’s rule.

1-1-4.1- Apply principles of organic chemistry to explain the chemical reactivity

and synthesis of the different organic compound classes.

1-1-4.2- Discuss and explain of the mechanism of different organic reactions

utilizing his understanding of principles of organic.

2-2-4.2- Design a reasonable chemical method to prepare organic

4-1-2- Demonstrate capability to manage his time effectively.

4-1-3- Retrieve, gather, evaluate analyze data from different.

 I- Structure of Benzene
1- Discovery of Benzene
In 1825, Michael Faraday isolated a pure compound of boiling point 80 oC from the
from illuminating gas, the fuel burned in gaslights from (whale oil).
▪ Mol. Formula :
C6H6 (low hydrogen-to-carbon ratios) ... highly unsaturated
▪ Reactions:
1- Reacts with substitution rather than addition (the common reactions of
the unsaturated hydrocarbons).
2- Give only one monosubstitution product (all H atoms are equivalent).

3- Benzene is remarkably stable, not undergo addition reaction & oxidation

reactions (While alkenes & alkynes were unstable towards these reactions).
... benzene does not show the behavior expected of a highly unsaturated compound
 I- Structure of Benzene
2- Kekule structure
Kekule proposed a cyclic structure for benzene with three alternating double bonds

▪ Advantages of Kekule structure:

Kekule structure explain Mol. Formula (C6H6 ) & high unsaturation & formation
of monosubstituted benzene.
▪ Drawbacks of Kekule structure: Kekule structure cannot explain
1- Extra stability of benzene.
2- Benzene reacts with substitution rather than addition (although has 3
double bonds).
3- Kekule structure predicts (for example), two different 1,2-
dichlorobenzenes, but only one is known to exist.
 I- Structure of Benzene

Explanation: 1,2-dichlorobenzene has two

& possible Kekule’s structure while only one
structure already exist

4- In a Kekule structure, the C-C single bonds would be longer than the double
bonds, while benzene ring showed all the bonds are the same length (1.397 Ao)

While 6 C-C bonds of benzene ring of same length (1.397 Ao) that is intermediate value
between double & single bond lengths
 I- Structure of Benzene
3- Resonance explanation of the benzene structure
❑ Benzene is actually a resonance hybrid of the two Kekule structures, in them
the three π bonds are delocalized over the ring, that could be written as circle
in the hexagon.

2 Kekule resonance structures Hybrid structure drawn as

circle in the hexagon

❑ The Molecular Orbital Explanation of the structure of benzene: -

▪ Benzene is a planar symmetrical hexagon with bond angle 120o
and C–C bond length 1.39 Ao (i.e. intermediate between–C and C=C).
 I- Structure of Benzene
- There are two types of bonding in benzene:
➢ σ-Bonding:
▪ Each C is sp2 hybridized and uses 3 sp2 orbitals to form 3 σ bonds (2 σ
bonds with 2 sp2 orbitals of the 2 adjacent carbon atoms and one σ with
1s orbital of H atom) a
▪ All C’s are planar.

➢ π-Bonding

▪ Each carbon has p orbital perpendicular to the plane of the ring.

▪ Each p orbital can overlap equally with each of the two adjacent p
orbitals i.e. C1 can overlap with each of C2 and C6.
▪ Overlap of all 6 p orbitals occurs to form delocalized molecular orbitals
(MO) containing 6 π electrons.
 H H
π
σ σ

σ
H σ σ σ σ
H ≡
σ σ
σ
π π
σ σ
H
H

≡
● As a result Benzene is generally represented by the combined contributions of
its two resonance structures (Kekulé structures).
● When combined, the C-C bonds are neither single or double bonds but
something intermediate.
4- Stability of benzene
by measuring heats of hydrogenation, hence Hydrogenation of alkenes is
exothermic reaction.

Hydrogenation of cyclohexene (only one C꞊C)

Hydrogenation of cyclohexadiene (two C꞊C)

While hydrogenation of cyclohexadiene resulting in

Energy equal nearly twice that of cyclohexene
Hydrogenation of benzen (three C꞊C)

Resulted in E less than expected

[3×-28.6 = -85.8 Kcal/mol]

... benzene has lower energy content (i.e. more stable) than the imaginary 1,3,5–
cyclohexatriene by 36 Kcal/mol.

5- Resonance Energy of Benzene

● Delocalization of 6 π electrons over cyclic conjugated system (resonance)
result in increased stability of the benzene structure (more stable than 1,3,5-
cyclohexatriene).
➢ Failures of the Resonance explanation:
Fail to explain why have not all the cyclic hydrocarbons with alternating single and
double bonds that called annulenes the same stability of benzene.

▪ Although, cyclobutadiene and cyclooctatetraene are conjugated rings (with

alternating double & single C-C bonds) & can also be represented by resonance
structures like benzene, cyclobutadiene and cyclooctatetraene are not stable and
have properties typically associated with alkenes and cyclobutadiene is very
unstable

React by addition reaction rather than substitution,

Not stable
So not aromatic
6- Requirements for Aromaticity according to
Molecular Orbital Theory (Hucle’s Rule)
The compound to be aromatic it must be
1-Cyclic
2-Fully conjugated (all C atom sp2 hybridized).
3-Planar. if the compound does not satisfy condition 1→3,
it will be non aromatic

while if the compound satisfy all condition 1→3,

4-Follow Huckel’s rule
a- if the compound has 4n+2 π (where n is integer number i.e. n
= 0,1,2,3 ….) it will be aromatic.

b-if the compound has 4n π (where n is integer number i.e. n =

0,1,2,3 ….) it will be antiaromatic.
•Application of Huckel’s rule
1) Benzene: 3 π bonds, each has 2 π electrons
Cyclic, conjugated, planar ... 3 × 2 = 6 π electrons

Contain 6 π electrons
w\ represent 4n+2; n=1
... Aromatic

2) cyclobutadiene: 2 π bonds, each has 2 π electrons

Cyclic, conjugated, planar ... 2 × 2 = 4 π electrons

Contain 4 π electrons
w\ represent 4n; n=1
... Antiaromatic

3) Cyclooctatetraene:
Cyclic, conjugated, non-planar
... nonaromatic
N.B. For the planarity of cyclic compounds; all Cyclic, Conjugated, 3- or 4- or 5-
or 6-membered rings are Planar

Cyclopentadiene:
Cyclic, not conjugated (not all Cs sp2)
... Nonaromatic
➢ For Aromatic ions:
Cyclopentadienyl anion:

- Carbon atom becomes sp2 hybridized

- The two electrons left behind can occupy the

new p orbital
- new p orbital can overlap with the p orbitals
- Carbanion C has pair of 2 π electrons on either side, so six p electrons become
delocalized

Cyclopentadienyl anion:
Cyclic, conjugated, planar
Contain 6 π electrons
w\ represent 4n+2; n=1
... Aromatic
Cycloheptatriene: Cycloheptatrienyl cation:
Cyclic, not conjugated (not all Cs Cyclic, conjugated (all Cs is sp2),
is sp2) planar, Contain 6 π electrons
... Not Aromatic w\ represent 4n+2; n=1
... Aromatic

Cyclopropenyl cation:
Cyclic, conjugated, planar
Contain 2 π electrons
w\ represent 4n+2; n=0
... Aromatic
Cycloheptatrienyl anion:
Cyclic, conjugated, planar
Contain 8 π electrons
w\ represent 4n; n=2
... Antiaromatic

➢ Heterocyclic ring (contain O, N, S)

Pyrrole:
Cyclic, conjugated, planar
Contain 6 π electrons
w\ represent 4n+2; n=1
... Aromatic
Lone pair of electrons in P orbital,
So available for overlapping with 4 π
... Total No of π electrons = 6 π e
Pyridine: 6 parallel p orbital each
contain one π electron

lone pair of electrons present in sp2

orbital perpendicular to the π system
Pyridine :
Cyclic, conjugated, planar
Contain 6 π electrons
w\ represent 4n+2; n=1
... Aromatic

N.B. For considering the aromaticity of heterocyclic rings:-

1- N, NH, S, O, Se all could be considered sp2 hybridized.
2- For rings with -N=, lone pair of electrons in present in sp2 orbital, so not
parallel with other π system (not be added to total value of π electrons).

3- For rings with -NH-, -O-, -S-, -Se-, lone pair of electrons present in p orbital so
parallel with other π system (be added to total value of π electrons).
Examine aromaticity of pyrimidine ring???

Annulenes
- monocyclic compounds having alternating single and double bonds.
- The ring size of an annulene is indicated by a number in brackets.

[10]annulene

Steric hinderence caused by 2 central H prevent the compound from gaining the
coplanarity required for aromaticity.
so compound non planar ... Non aromatic
▪ Explain whether the following compound cyclopentadienyl anion is aromatic,
antiaromatic or not aromatic?

.......................
.......................
.......................
.............................................
H

▪ Explain the aromaticity of naphthalene (planar)?

.....................
.....................
.....................
..................................
▪ Explain whether the following compound cycloheptatrienyl anion
is aromatic, antiaromatic or not aromatic?
(N.B. cycloheptatrienyl anion is planar)

.......................
.......................
.......................
.............................................

H
 Summary (i)
Structure of Benzene
Conflict of the expected structures of benzene Delocalization arise from overlapping of each p orbital of
a certain C atom equally with each of the two adjacent p
▪ Mol. Formula: C6H6... highly unsaturated orbitals
▪ Reacts with substitution rather than addition Resonance Energy of Benzene
& give monosubstituted product
● the stability acquired due to Delocalization of 6 π electrons
▪ Benzene is stable, not undergo oxidation & over cyclic conjugated system (resonance).
reduction reactions
❑ Requirements for Aromaticity according to
... benzene does not show the behavior expected Molecular Orbital Theory (Hucle’s Rule)
of a highly unsaturated compound
The compound to be aromatic it must be
Kekule structures 1-Cyclic
explain Mol. Formula (C6H6 ) & formation 2-Fully conjugated (all C atom sp2 hybridized).
of monosubstituted benzene. 3-Planar.
Extra stability if not satisfy any of conditions 1→3, ... non aromatic
Not explain
Reacts with substitution 4-Follow Huckel’s rule
a- if compound has 4n+2 π it will be aromatic.
rather than addition. (i.e has No of π electrons = 2 or 6 or 10 or 14 & soon)
Why 1,2-dicsubstituted benzenes, have only one
b-if compound has 4n π it will be antiaromatic.
structure exist rather than expected 2 isomers
(i.e has No of π electrons = 4 or 8 or 12 or 16 & soon)
Why 6 C-C bonds of benzene
ring of same length (n is integer No i.e. n = 0,1,2,3 ….)
N.B. For considering the aromaticity of ions:-
Resonance explanation of the benzene structure ❑ Carbanions C has pair of 2 π electrons while cations has
Benzene is a hybrid of the two Kekule structures, with 3 π vacant orbital (0 π electrons )
bonds are delocalized over the ring. N.B. For considering the aromaticity of heterocyclic rings:-
1- N, NH, S, O, Se all could be considered sp2 hybridized.
2- lone pair of electrons of heteroatom if present in sp2 orbital not
enter in the π system while if in P orbital will enter.
II- Nomenclature of Benzene Derivatives
1- Monosubstituted benzenes:
1- For substituent -Cl, -Br , -I , -NO2 →prefix the name of substituent to the
word benzene.
I NO2
Cl Br

Chlorobenzene Bromobenzene Iodobenzene Nitrobenzene

2- Other substituent give common name to compound. e.g.

CH3 OH COOH
NH2

Toluene Aniline Phenol Benzoic acid

 SO3H CHO

Benzenesulphonic acid Benzaldehyde

II- Disubstituted benzenes:

● When 2 substituent occur in the ring → 3 isomers are possible
ortho-, meta-, para-
 Br Br Br

e.g. Br

Br

Br
o-dibromobenzene m-dibromobenzene p-dibromobenzene

● If the 2 substituent are different & both not give special name to the
molecule → name the two groups successively (alphabet.) + word benzene.
I
NO2

Cl
Br
p-Bromoiodobenzene m-Chloronitrobenzene

● If one of the 2 substituent can give the ring special name

→ the molecule is named as derivative of that special compound.
e.g.
 OH

CH3 COOH

NO2

Br Cl

o-nitrotoluene p-bromophenol m-chlorobenzoic acid

● If the 2 substituent can give the ring special name

→ the molecule is named as derivative of that special compound of higher priority.

Order of priority of Functional groups:

N.B.
* Carboxylic acid group (COOH) higher priority than
hydroxy group (OH);
Parent name: benzoic acid, use name “hydroxyl” for
(-OH group) as prefix.
** Begin numbering from carbon attached to COOH
m-hydroxybenzoic acid (higher priority group).
 * Carbaldehyde group (CHO) higher priority than
amino group (NH2);
Parent name: benzaldehyde, use name “amino” for
(-NH2 group) as prefix.

o-aminobenzaldehyde NOT o-anilinebenzaldehyde

* Acetyl group (COCH3) higher priority than

hydroxy group (OH);
Parent name: benzaldehyde, use name “hydroxyl” for
(-OH group) as prefix.

m-hydroxyacetophenone NOT o-Phenolacetophenone

o-aminophenol
❑ When the benzene ring is named as a substituent on another molecule, it is
called a phenyl group, and it is often abbreviated Ph.

1-Phenyl-2-butyne
III- If three or more substituents on the benzene ring,
▪ Numbers are used to indicate their positions. Assign the numbers to give the
lowest possible numbers to the substituents.
▪ The carbon atom bearing the functional group that defines the base name (as
in phenol or benzoic acid) is assumed to be C l.

3,5-dihydroxybenzoic acid
1,3,5-trinitrobenzene
(COOH higher priority than
OH)

4-chloro-1,2-dinitrobenzene
Not 2,4-dinitrophenol
1-chloro-3,4-dinitrobenzene
2-bromo-1-chloro-3-nitrobenzene 2-chloro-6-nitrophenol
NOT NOT
2-bromo-3-chloro-1-nitrobenzene 6-chloro-2-nitrophenol

4-bromo-2-nitrobenzoic acid
NOT
4-bromo-6-nitrobenzoic
 p-methylphenol
NOT
p-toluenephenol
Not 3,4-dinitrophenol p-bromobenzoic acid
p-hydroxytoulene
 Summary (ii)
II- Nomenclature of Benzene Derivatives
1- Monosubstituted benzenes: ● If 2 substituents are different & both not give special name
1- For substituent -Cl, -Br , -I , -NO2 →prefix the → name the two groups successively (alphabet.) + word benzene.
name of substituent to the word benzene. I
NO2

Cl
Br

2- Other substituent give common name to p-Bromoiodobenzene m-Chloronitrobenzene

compound. e.g. ● If one of the 2 substituent can give the ring special name
→ the molecule is named as derivative of that special compound.

If the 2 substituent can give the ring special name → the molecule
is named as derivative of that special compound of higher priority.
Order of priority of Functional groups:

II- Disubstituted benzenes:

3 isomers are possible ortho-, meta-, para-
m-hydroxybenzoic acid
➢ Test your self:
Q1: Give IUPAC name for the following compounds:
NH2 CH3
COOH
OH CH2CH2CH3

Cl

Br
Cl I
NO2
F

Q2) Draw structures corresponding to the following names

(a) 3-Methyl-2-nitrobenzoic acid (d) Benzene-1,3,5-triol
(b) 3-Methyl-2-phenylhexane (e) p-Iodonitrobenzene

(c) o-Aminobenzoic acid (f) 4-bromo-2-nitrotoluene

Q3: Determine which of the following compounds are aromatic, antiaromatic or non-
aromatic and explain why????