Pharmaceutical organic chemistry Best pdf

1. BENZENE AND
DERIVATIVES
BY
K.NITHYAKALYANI..M.PHARM
ASSITANT PROFESSOR

2. INTRODUCTION
Benzene and other aromatic compounds are conjugated
cyclic polymers. Their chemical reactivity and physical properties differ
significantly from linear conjugated and nonconjugated mono- and
polyenes. Ethylene and conjugated 1,3-butadiene react readily with
bromine and chlorine at room temperature to yield halogenated products.
Benzene reacts with bromine and chlorine, in the presence of catalyst to
yield the substitution product.
Benzene undergoes substitution reactions rather than
addition reactions, with many reagents. Substitution reactions include:
halogenation, sulphonation, nitration, alkylation and acylation. These
reactions are common to various aromatic compounds. This discussion
will be limited to benzene as a model aromatic compound. Benzene is
considered as the parent compound of aromatic hydrocarbons. The
chemical formula of benzene is C 6 H 6 . Faraday in the year 1825
isolated benzene from illuminating gas cylinders. The name benzene was

3. NOMENCLATURE OF AROMATIC
COMPOUNDS
The following are the important rules for assigning systematic
names to the derivatives of benzene:
1. The word root for benzene derivatives is benzene.
2. In case of monosubstituted benzenes, the name of the
substituent group is added as a prefix to the word root

4. EXAMPLE:
Chlorobenzene

5. ISOMERISM OF BENZENE DERIVATIVES
Arenes show positional isomerism as discussed
below. Benzene is a symmetrical molecule. Therefore, the
replacement of one hydrogen atom of benzene by any
substituent will give only a single product. Thus, mono-
substitution products of benzene do not show isomerism . Thus,
di-substitution products of benzene show positional isomerism .
These three isomers are called ortho ( o -), meta ( m -) and para
( p -) accordingly as the relative positions of the two substituents
are 1,2-, 1,3- and 1,4-, respectively.

6. Besides the three dimethylbenzenes, the fourth
isomer, ethylbenzene, is also known.
Thus, the three positional isomers of
dimethylbenzene or xylene are as
follows:

7. If the number of substituents increases
in the benzene ring, the number of
positional isomers also goes up. In
case of bicyclic arenes such as
naphthalene, even monosubstituted
compounds show position isomerism.

8. EXAMPLE :
With higher arenes, the number of
possible position isomers also
increases

9. PREPARATION OF BENZENE
COMMERCIAL PREPARATION OF BENZENE
When coal undergoes destructive distillation, the following important products
are formed:
1.Ammoniacal liquor
2.Coal gas
3.Coal tar
4.Solid residue
Benzene is a fraction of coal. It is collected when coal tar is
subjected to further distillation. Benzene is collected between 80 and 81°C.
Light oil (first fraction), which is lighter than the water, is treated with
sulphuric acid to remove basic impurities and washed with water and treated
with sodium hydroxide solution to remove excess sulphuric acid and phenol.
Finally it is washed with water and subjected to fractional distillation. The first
fraction (collected up to 110°C) and the second fraction (110–140°C)

10. PROPERTIES OF BENZENE
PHYSICAL PROPERTIES OF BENZENE
Learning Plus Prior to the 1920s, benzene was frequently used
as an industrial solvent, especially for degreasing metal. As its toxicity
became obvious, other solvents replaced benzene in application that directly
exposed the user to benzene.
1. It is a colourless liquid.
2. Benzene in organic solvents but immiscible in water.
3. It is an aromatic compound so it has a typical aromatic odour. ( Aroma in
Greek means pleasant smell.)
4. It burns with sooty flames it contains high amount of carbon.
5. It has density of 0.87 g cm −3 . It is lighter than water.
6. Its melting is point 5.5°C and boiling point is 80.5°C. For homologous
series, it increases with the increasing molecular mass because of the
increase in magnitude of van der Waals forces of attraction.
7. All the carbon–carbon bonds in benzene are of same length, which is

11. STRUCTURE OF BENZENE
LET US NOW DISCUSS THE STRUCTURE OF THE SIMPLEST ARENE, I.E. BENZENE.
Kekule Ring Structure of Benzene
The molecular formula of benzene is C 6 H 6 , which suggests
that it is an unsaturated compound. But it does not undergo the
usual reactions of open chain unsaturated compounds. Rather it
takes part in substitution reactions such as halogenation and
nitration. However its adds three molecules of hydrogen,
halogens and ozone indicating the presence of three double
bonds in it. It forms only one type of monosubstitution product
showing similar nature of all the six carbon atoms.

12. Learning Plus Kekule was the first to deduce the ring structure of
benzene; after years of studying carbon bonding, benzene and related
molecules, the solution to the benzene structure came to him in a
dream of a snake eating its own tail. Upon waking, he was inspired to
deduce the ring structure of benzene.
All the above facts led Kekule to propose a ring structure for benzene.
He postulated the structure as follows:
1. The six carbon atoms in benzene are located at the six corners of a
hexagon and each carbon is attached to one hydrogen atom.
2. The six carbon atoms are linked to one another through alternate
single and double bonds to account for the fourth valency of each
carbon, as shown in the structure below:

13. LIMITATIONS OF THE RING STRUCTURE
Although Kekule structure of benzene has been supported by
many evidences, yet it has the following shortcomings:
1. Since this structure contains three double bonds, the chemical
properties of benzene should resemble those of alkenes. But
actually it is not so. Benzene is highly stable and forms
substitution compounds easily.
2. Kekule structure predicts two types of bond lengths, i.e. for
single bonds (C — C), 1.54 Å and for double bonds (C C) 1.34
Å. Actually all the bonds of benzene are of equal length (1.39
Å).

14. 3. According to Kekule structure, two o -disubstituted
products of benzene are possible.
But only one o -dihalobenzene is known. However,
these can easily be explained in terms of resonance and
molecular orbital theories of benzene.

15. RESONANCE STRUCTURE OF BENZENE
IN THE LIGHT OF RESONANCE THEORY, BENZENE CAN BE REPRESENTED AS A
RESONANCE HYBRID OF THE FOLLOWING TWO KEKULE STRUCTURES:
Facts in support of resonance structure of
benzene
1. Carbon–carbon bond length: X-ray analysis and electron
diffraction studies show that all the carbon–carbon bonds in
benzene are of exactly same bond length, i.e. 1.397 Å. This
value of bond length lies between carbon–carbon single bond
in ethane 1.54 Å and the double bond 1.34 Å as in ethylene.

16. 2. Stability: The actual molecule of benzene is more
stable than any of the Kekule structures. The extra
stability of benzene as a result of resonance is defined
as the difference in the energy content between a
hybrid molecule and the more stable contributing
structure.
The resonance energy of benzene can be
calculated on the basis of heat of hydrogenation.
The quantity of heat evolved when one mole of an
unsaturated compound is completely hydrogenated in
the presence of catalyst is known as heat of
hydrogenation.
The heat of hydrogenation of cyclohexene (six-
membered ring and one double bond) is 119.5 kJ mol
−1 . On this basis heat of hydrogenation of Kekule
structure (I or II) is expected to be 119.5 × 3 = 358.5
kJ mol −1 . However, when benzene (six-membered
ring and three double bonds) is fully hydrogenated, it
gives cyclohexane and 208.2 kJ mol −1 of heat is

17. Thus the heat of hydrogenation of benzene is 358.5 –
208 = 150.3 kJ mol −1 less than that of Kekule
structure. In other words, benzene is 150.3 kJ mol −1
or 36 kcal mol −1 more stable than if it were simply a
cyclic conjugated triene. This is the resonance energy
of benzene.