PHARMACEUTICAL CHEMISTRY (ORGANIC)

Chapter 1

BASIC CONCEPTS
Two main classes of chemical compounds:
• Organic
• Inorganic
All compounds were classified on the basis of source
from which they were derived.
• Mineral origin---inorganic e.g. table salt, marble,
carbon dioxide
• Animal, vegetable---organic e.g. acetic acid (from
vinegar), alcohol (from wine), citric acid (from
lemons), sucrose (from sugarcane)
 Bond order
Bond order is the number of chemical bonds between a pair
of atoms and indicates the stability of a bond. For example, in
diatomic nitrogen, N≡N, the bond order is 3; in acetylene,
H−C≡C−H, the carbon-carbon bond order is also 3, and the
C−H bond order is 1. Bond order and bond length indicate the
type and strength of covalent bonds between atoms. Bond
order and length are inversely proportional to each other:
when bond order is increased, bond length is decreased.
 Bond Length

Bond length is defined as the distance between the centers of two covalently

bonded atoms. The length of the bond is determined by the number of bonded

electrons (the bond order). The higher the bond order, the stronger the pull

between the two atoms and the shorter the bond length. Generally, the length

of the bond between two atoms is approximately the sum of the covalent radii

of the two atoms. Bond length is reported in picometers. Therefore, bond

length increases in the following order: triple bond < double bond < single

bond.

(A picometer is one trillionth of a meter)

 Bond Energies

Atoms bond together to form compounds because in

doing so they attain lower energies than they possess
as individual atoms. A quantity of energy, equal to
the difference between the energies of the bonded
atoms and the energies of the separated atoms, is
released, usually as heat. That is, the bonded atoms
have a lower energy than the individual atoms
do. When atoms combine to make a compound,
energy is always given off, and the compound has a
lower overall energy.
• When a chemical reaction occurs, molecular
bonds are broken and other bonds are formed
to make different molecules. For example, the
bonds of two water molecules are broken to
form hydrogen and oxygen.
2H2O→2H2+O2
Energy is always required to break a bond, which
is known as bond energy. While the concept may
seem simple, bond energy serves a very
important purpose in describing the structure
and characteristics of a molecule. It can be used
to determine which Lewis Dot Structure is most
suitable when there are multiple Lewis Dot
Structures.
When a bond is strong, there is a higher bond
energy because it takes more energy to break a
strong bond.
When the Bond order is higher, bond length is
shorter, and the shorter the bond length means
a greater the Bond Energy because of increased
electric attraction. In general, the shorter the
bond length, the greater the bond energy.
 Inductive Effect

• To understand the inductive effect properly, we must know

about the nature of the covalent bond. There are two types of
covalent bonds, one is a non-polar covalent bond and another is
a polar covalent bond. A non-polar covalent bond is a bond that
is established between either two identical atoms or atoms
having almost the same value of electronegativity, for example,
H—H, N≡N, Cl—Cl, Br—Br etc. Due to the same
electronegativity, the shared electron pair of the covalent bond
is present at the center of the nuclei of both the bonded atoms.
Hence, the electron cloud is shared equally between these two
atoms. Therefore, the formation of two different poles does not
take place and thus the bond is said to be non-polar.
A polar covalent bond binds the two atoms with unequal
electronegativity. In this bond, the shared electron pair is not at
the center of the covalent bond but it is displaced towards the
more electronegative atom. Therefore, unequal distribution of
shared electrons takes place between these two atoms. As a
result, the electron density is increased towards a more
electronegative atom, leading to the generation of partial
negative charge (δ−) on it, whereas electron deficiency is found at
the less electronegative atom side which results in the generation
of partial positive charge(δ+) on it. Therefore, two opposite poles
(negative and positive poles) are generated in this type of
covalent bond and thus it is said to be a polar covalent bond.
For example, the chlorine atom is more
electronegative than hydrogen and thus the
shared electron pair is closer to the Cl-atom as
compared to the H-atom in the HCl molecule,
which leads to the formation of a partial
negative charge on chlorine and partial positive
charge on the hydrogen atom.
After understanding non-polar and polar
covalent bonds, it is now easy to understand the
inductive effect. The inductive effect can be
defined as the “Generation of polarity in a non-
polar covalent bond due to the presence of an
adjacent polar covalent bond”. It is also known
as the “Transmission effect”.
Let us consider the example of a carbon chain with a chlorine atom
attached to its terminal carbon. To understand the example
systematically, number 1 is assigned to the carbon attached to the
chlorine, and numbers 2, 3, and 4 are assigned to the consecutive
carbons. As the electronegativity of chlorine is greater than that of
carbon, the chlorine attracts the electrons of the C1–Cl covalent bond,
causing the shared electrons of the bond to be displaced towards the
chlorine atom and the electron density around the chlorine atom gets
increased. As a result, a partial negative charge is generated on the
chlorine atom and the same amount of positive charge is generated on
the C1 atom due to electron deficiency. Hence, the C1–Cl bond becomes
polar.
Since the bond formed between two identical atoms is
non-polar, the bond formed between C 1 and C2 must be
non-polar. But due to the polar nature of the C 1–Cl bond,
the positive charge on C1 attracts the electrons of the C1–
C2 covalent bond, and thus the electrons of the C 1–
C2 bond are displaced towards C1 leading to the
generation of electron deficiency on C 2 atom i.e. a partial
positive charge is generated on C2. But this partial positive
charge on C2 is less than the positive charge generated on
C1.
Similarly, electron-deficient C2 pulls electrons
from C2–C3 bond, and the C3 atom attracts
electrons from C3–C4 bond. As a result, partial
positive charges are generated on all these
carbon atoms but the extent of the positive
charge gets weaker while moving from C1 to C4.
Therefore, it can be concluded that due to the C1–Cl
polar covalent bond, polarity is generated in C–C non-
polar covalent bonds viz C1–C2, C2–C3, and C3–C4 bonds.
This phenomenon is known as the inductive effect (I-
effect). The inductive effect exists in a molecule even
when no other chemical species are present or the
molecule is not participating in the chemical reaction
and thus it is a permanent effect. It is to be noted that
only the σ electrons are displaced in this effect and
not the π electrons.
Types of inductive effect
There are two types of inductive effect:
1.Negative inductive effect or –I effect
The atoms or groups which pull the electron density
while showing an inductive effect are called the –I
groups and the inductive effect of such groups is called
the negative inductive effect (–I effect). Such
groups/atoms are generally more electronegative or
electron-attracting than the H atom. Few atoms/groups
in decreasing order of their –I effect are shown below:
2. Positive Inductive effect or +I effect
The atoms or groups having electron
repelling/releasing tendency while showing
inductive effect are called +I groups and the
inductive effect induced by them is called the
positive inductive effect (+I effect). Such groups have
generally less electronegativity i.e. more electron
repulsion ability than the H atom. Few atoms/groups
showing the +I effect are mentioned below in their
decreasing order: