50

Course materials in Italics and the larger chemical structures in the section are from the
following book with permission to use in any format (https://authors.library.caltech.edu/25032/:
Organic chemistry: Methane to macromolecules
Copyright© 1971 by W. A. Benjamin, Inc.
New York, New York 1001
All rights reserved
Standard Book Number 8053-8332-8
Library of Congress Catalog Card Number 71-!30356 Manufactured in the United States of
America 12345K54321
W. A. BENJAMIN, INC.

4.4. Aromatic Chemistry

Several organic compounds with distinct smells were described as "aromatic compounds" in
the early days of organic chemistry (circa 1855). The first aromatic compounds that were
discovered were benzene and its derivatives. Derivatives are compounds that are derived from
a "parent compound", such as benzene, but with one or more different substituents. An example
of such a compound is benzaldehyde that has a distinct almond smell. However, with time, the
word aromatic has become associated with a group of compounds that have distinct chemical
and physical properties based on their electronic structure.
Many biologically relevant molecules, as well as drug molecules, have aromatic parts. Amino
acids such as tryptophan, phenylalanine, histidine and tyrosine all have aromatic parts. The
nucleotides that are building blocks of RNA and DNA are also aromatic. Many drug molecules
also have aromatic parts, for example, sertraline, ibuprofen and chlorpromazine. A pharmacist
needs to have a foundation in aromatic chemistry in order to understand the synthesis,
metabolism, degradation and interaction with biomolecules such as proteins in the human body.

H CH3
N
S
CH3

Cl N OH
CH3
O
H3C
CH3
N
Cl
CH3
Cl

chlorpromazine
sertraline ibuprofen
(a phenothiazine derivative)
an antidepressant an anti-inflammatory
an antipsychotic
 51

Activity 4.4.1

Circle the parts that all three of the molecules at the bottom of the previous page have in
common.

4.4.1. Aromaticity
The history of aromatic compounds is fascinating. Scientists isolated a compound with a
molecular formula of C6H6 which indicated that it was highly unsaturated. Unsaturated means
that it has fewer hydrogen atoms than a compound with only carbon and hydrogen atoms where
all the bonds are singles. Unsaturated molecules can have double or triple bonds or both. They
are formed when a molecule loses sets of two hydrogen atoms at a time. An example of a
saturated compound is hexane with a molecular formula of C6H14. In contrast, unsaturated
compounds have one or more double bonds, for example, hexene with a molecular formula of
C6H12.

ACTIVITY 4.4.1.1.
HC
CH2 CH2 CH3 CH CH CH3 CH CH CH2 C CH CH2
H3C CH2 CH2 H2C CH CH2 H2C CH CH CH CH

hexane (3E)-hexa-1,3-diene (3E)-hexa-1,3,5-triene (3E)-hexa-1,3-dien-5-yne

Write the molecular formula for each of the above compounds underneath the name of each
compound. How many hydrogen atoms are removed each time moving from left to right in the
sequence above?
All the molecules above are also very reactive; for example, they readily react with Br2 to form
addition products. Scientists were perplexed by the fact that the molecule with the molecular
formula of C6H6 which they called benzene, did not readily react with Br2. They realised that
it must have a different structure and considered many options. One of the people studying the
structure of this new compound was August Kekulé. He proposed a ring structure for benzene
consisting of the following two structures:
 52

Apparently, he had a dream in which it looked like a snake that was biting its tail:

(By Haltopub - Own work basé sur Benzene Structural diagram.svg et Ouroboros-simple.svg, CC BY-SA 3.0,
https://commons.wikimedia.org/w/index.php?curid=29661966)

Let us consider the two structures that Kekulé proposed:

Later on, scientists were able to measure the bond lengths in the molecule and discovered that
all the C-C bonds in benzene had the same length. It was contrary to the fact that a single bond
is longer than a double bond. In order to explain this phenomenon, they used molecular orbital
theory. They proposed a conjugated system in the ring where all the carbon atoms are sp2-
hybridised with parallel, overlapping p-orbitals. It creates two spaces that are doughnut-shaped.
One is above, and the other is below the molecule, in which the electrons in the π-bonds can
move:

By Vladsinger - Own work by uploader, based on en:File:Benzene-orbitals2.png, CC BY-SA 3.0,

https://commons.wikimedia.org/w/index.php?curid=7531044

A way to think about this is that the electrons are so busy moving in the circular spaces, that
they are not interested in reacting with compounds similar to other alkenes. In more scientific
terms we say that the electrons are delocalised due to resonance energy.
 53

It would, therefore, be correct to consider the two structures that Kekulé proposed as resonance
forms. We can represent that by putting a double-headed arrow between them, meaning that
they are essentially two forms of the same molecule:

Today there are several ways in which we draw benzene rings:

Scientists continued to study benzene and similar derivatives, and in the 1930s, Erich Hückel,
a German Chemist and some of his fellow chemists developed Hückel's 4n+2 rule. Also, they
established criteria that can be used to determine whether a compound is aromatic or not:
a) It must be cyclic, i.e. have a ring structure.
b) It must be planar or very close to planar so that the p-orbitals can overlap in order to
form a conjugated system.
c) All the atoms in the ring must be sp2-hybridised. Please note that carbocations are sp2-
hybridised. Carbanions are usually sp3-hybridised, except when they are in a conjugated
system, such as in an aromatic compound. Carbanions also have a lone electron pair
that should be added to the number of π-electrons of the conjugated system.
d) It must have 4n+2π electrons in the ring. "n" can be any integer, including zero. It makes
it easy to determine how many electrons one must look out for when determining
whether a compound is aromatic or not. Below is a table with the 4n+2 values already
calculated for n=0 to n=4. It can also be calculated for larger numbers. You can see that
if a molecule has 2 or 6 or 10, or 14 electrons and conforms to the rules a) to c) above,
it will be aromatic.

4n + 2
n (number of electrons that must be
in the conjugated system.)
0 2
1 6
2 10
3 14
4 18

Compounds that comply with rules a) to c), but have 4n π electrons, are antiaromatic.
All other molecules are not aromatic.
 54

ACTIVITY 4.4.1.2
State whether the following compounds are aromatic, antiaromatic or not aromatic. You may
assume that they are all planar. Give reasons for your answers in terms of ALL four criteria for
aromaticity.
 55

4.4.2. Nomenclature

A variety of substituted benzenes are known with one or more of the hydrogen atoms of the ring
replaced with other atoms or groups. In almost all of these compounds, the exceptional stability
associated with the benzene nucleus is retained. A few examples of" benzenoid" hydrocarbons
follow, and it will be noticed that the hydrocarbon substituents include alkyl, alkenyl, alkynyl,
and aryl groups.

Several aromatic compounds have common names that are still in frequent use today. The
compounds that you will encounter the most are:

H3C O H O HO O
CH3 OH NH2

toluene phenol aniline acetophenone benzaldehyde benzoic acid

ACTIVITY 4.4.2.1
Draw chemical structures for bromobenzene, nitrobenzene (nitro = -NO2), chlorobenzene,
propylbenzene:
 56

The naming of these hydrocarbons is relatively straightforward. Each is named as an alkyl,

alkenyl, or arylbenzene unless for some reason the compound has a trivial name. The
hydrocarbon group (C6H5 -) from benzene itself is called a phenyl group and is sometimes
abbreviated as the symbol ϴ or as Ph. Aryl groups, in general, are often abbreviated as Ar.
An aryl group in nomenclature is also used to indicate to which group a benzene ring is attached;
for example, another name for chlorobenzene is aryl chloride. One will often wee the word aryl
halide for a benzene ring that has a halogen attached to it. Similarly, you will see terms such
as arylamine and aryl ketone.
Benzenes can also be called arenes.

ACTIVITY 4.4.2.2
Draw the structures of 2-phenyl-hexane and 3,5-diphenyl-heptane.

There are two methods for naming benzene rings with two substituents.
The first method describes the relative positions of the substituents. Usually, the names for the
more common benzene derivatives at the bottom of page 55 are used in this method. For
example, if a bromine substituent is directly next to the methyl group of toluene, it will be
called ortho-bromotoluene, as in the structures below:
 57

The name of the compound will not change if you draw it in a different orientation, for example,
all the structures below are called meta-chloro-aniline:
NH2 Cl
NH2
Cl

H2N
Cl NH2
Cl

The second method is executed by number the carbon atoms on the benzene ring. The name of
each substituent is included. Note that the common names such as toluene and aniline are not
always used in this method:

Ortho-dimethylbenzene meta-dimethylbenzene para-dimethylbenzene

When benzene rings have more than two substituents, the carbon atoms on the ring are
numbered in such a way that the substituents will all have as low a number as possible.
However, you will often find some discrepancies in this method in several textbooks.
Below are two different but acceptable names for the same compound.
Note that the name of the left-hand compound is based on the name methylbenzene. The
numbering was chosen to give the lowest numbers to all the substituents. In the name itself, the
substituents appear in alphabetical order.
The name of the right-hand compound is based on the common name aniline. Therefore, the
carbon atoms attached to the amino group is number one. The numbering order then moves
around the ring to give all the substituents the lowest possible numbers.

NH2 NH2

5 4 3 6 1 2

6 1 5 4
2 Cl 3 Cl
CH3 CH3
4-amino-2-chloro-1-methylbenzene 3-chloro-4-methylaniline
 58

You will be expected to:

a) give acceptable names to benzene derivatives
b) match a structure and its name

ACTIVITY 4.4.2.3

Here are some example questions from previous examination papers:

1. The correct name for the following compound is: (1)

HO
Cl
a) meta-chlorophenol
b) ortho-chlorophenol
c) para-chlorophenol
d) ortho-chlorobenzyl alcohol

2. The correct name for the following compound is: (1)

Br

Br
NH2

a) 1,4-dibromo-2-aniline
b) 2,5-dibromoaniline
c) 3,6-dibromoaniline
d) 1,4-dibromo-3-aniline
 59

3. The structure for 4-amino-2-chlorophenol is: (1)

a) Cl b) H
OH
O

NH2 Cl
NH2

c) OH d) OH
Cl Cl

NH2 NO2

4. The structure for 3-chloro-4-nitrobenzoic acid is: (1)

a) b) Cl OH
OH
O2N O
O
O2N

Cl

c) d)
OH H

Cl Cl
O O

O2N O2N

Answers:
1. b)
2. b)
3. c)
4. c)