CHAPTER-1

1) 1-BASIC CONCEPTS
2) Chemical Bonding (concept of hybridization)
3) Hydrogen Bonding
4) Conjugation
5) Hyper-conjugation
6) Inductive effect
7) Electromeric Effect
8) Resonance (mesomerism)
9) Steric effect
10) Effect of structure on reactivity of compounds
11) Tautomerism of carbonyl compounds
12) Nomenclature of organic compounds
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.1
Dated 01-02-
2022
 Chapter N0.1

Basic concept of organic

chemistry

1-Chemical Bonding
(concept of Hybridization)
Carbon
Carbon
Carbon electron orbitals
Electron disribution in
orbits
Ground vs excited state
 1-Chemical Bonding
Lewis and Koasel
Accept inert gases which have either 2 or 8
electrons in valence orbit all other have incomplete
valence orbits and lead to complete them by
combination to other atoms. In other words
stability
“There is urge to complete that
incomplete orbit like inert gases
which leads to chemical
combination”
 Types of Bonds
 ionic or electrovalent
Bonding

 Covalent Bond

 Co-ordinate Bond
Ionic or Electrovalent Bonding

 ionic bond, also called electrovalent

bond, type of linkage formed from
the electrostatic attraction between
oppositely charged ions in a
chemical compound. Such a bond
forms when the valence
(outermost) electrons of one atom
are transferred permanently to
another atom.
How electrovalent bonding
occurs
Ionic bonding
 Covalent Bond
 The elements of groups in middle of periodic
table like boron,carbon and nitrogen do not form
ionic bonds. Covalent bonds are formed by
mutual sharing of electrons
 Both of which are short of electron

“covalent bond, in chemistry,
the interatomic linkage that
results from the sharing of an
electron pair between two
atoms. “
Covalent sharing of
electron
Types of covalent Bonds

 Sigma bond

 Pi- bond
 Co-ordinate Co-valent
Bond
 A coordinate bond (also called a
dative covalent bond) is a covalent
bond (a shared pair of electrons) in
which both electrons come from the
same atom. A covalent bond is
formed by two atoms sharing a pair
of electrons. The atoms are held
together because the electron pair
is attracted by both of the nuclei.
 Recent interpretation of
Covalent Bond
 According to lewis theory in 1916 when
atoms combine to form molecules they
attain attain electronic configurationration
like inert gases.
 We simply represent it by a short line lrike
as unde
 Hydrogen Bonding
 hydrogen bonding, interaction involving a
hydrogen atom located between a pair of
other atoms having a high affinity for
electrons; such a bond is weaker than an ionic
bond or covalent bond but stronger than van
der Waals forces.
 A hydrogen bond is formed when the positive
end of one molecule is attracted to the
negative end of another.
 Application of Bonding in
Pharmacy
 It is becoming increasingly
important in drug design, but is
usually at odds with good oral
absorption. The formation of
intramolecular hydrogen bonds in
drug molecules is hypothesised to
shield polarity facilitating improved
membrane permeability and
intestinal absorption.
 Intermolecular forces are
 Application
 Drugs interact with receptors by
means of chemical bonds. The three
major types of bonds are covalent,
electrostatic, and hydrophobic.
 Modern Theory
 According to modern theory it is believed
that electrons have wave like properties
 Wave length

 Frequency

As well as properties of particles like

Mass
Energy
Momentum
So due to both properties its uneasy to
specify position and momentum of electrons
 Orbitals
 Electrons in an atom surround positively
charged nucleus and found in energy levels
called orbitals

 So orbital is region
where the
probability of finding
electron is maximum
Shapes of orbitals
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.2
Dated 02-02-
2022
Hybridization
 Orbitals
 Electrons in an atom surround positively
charged nucleus and found in energy levels
called orbitals

 So orbital is region
where the
probability of finding
electron is maximum
Ground vs excited state
Concept of hybridization
 Hybridization
 The process of mixing of pure orbitals to
give a set of new equivalent orbitals is
termed as hybridization
 sp3 1:3
 sp2 1:2
 sp 1:1
sp3 Hybrid orbitals
AlKANE(methane)
ALKENE(ETHENE)
ALKYNE( ETHYNE)
 Hybridization of Oxygen in
water
 The molecular structure of water
is consistent with a tetrahedral
arrangement of two lone pairs and
two bonding pairs of electrons.
Thus we say that the oxygen atom
is sp3 hybridized, with two of the
hybrid orbitals occupied by lone
pairs and two by bonding pairs.
Water molecule
tetrahedral
Hybridization of Nitrogen
 The nitrogen
is sp3hybridized which means
that it has four sp3 hybrid
orbitals. Two of the sp3hybridized
orbitals overlap with s orbitals
from hydrogen to form the two N-
H sigma bonds.
Application of Hybridization in
Pharmaceuticals
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.3
Dated 03-02-2022
Electronegativity
And induction effect
 Bonding in Light of modern
Atomic Structure
Consider when atoms are far apart. No force between them.
Consider when two atoms approach each other. What happens:
1-Electron clouds over lap.
2-Force of attraction between electrons in one atom and nucleus of other
atoms
3-the repulsion between electrons of both atoms
4-repulsion between nuclei of both atoms
5-so attraction and repulsion at same time.
6-the repulsive forces are significant at small distance
7-over-lap of atomic orbitals lowers energy.
8-energy is minimum when atoms bond
9-energy lowers until atoms so close that repulsion occurs and energy
increases.
 Electronegativity
 Electronegativity of an atom is measure of its power to
attract electrons that it is sharing in a covalent bond.
 When atom in a molecule are identical electrons are buried
in cloud between them and therefore both exert equal
attraction like H-H , Br-Br, Cl-Cl
 Usually electronegativity arises in molecule of different
atoms
 However when atoms in molecular orbitals are not identical
the electronic cloud which bonds two atoms is distorted
toward one atom which exerts great attraction like H-Cl ,
Cloud will be distorted toward more electronegative atom .
 Leads to polarity i.e. positive and negative poles
 So the molecule is said to be polarized
Electronegative Atom
Polarization
Molecular polarity
Ionic character of covalent Bond

 So the covalent bond are partially ionic if

they exist between two unlike atoms
which have different electronegativity
Polarity and Bond Length
 Electronegativity
 Depends upon
1- Atomic No.
2-Atomic Radii

Rule: atoms with higher atomic no less atomic

radii are more electro negative
In periodic table as u read toward right in a
particular horizontal row electronegativity
gradually increases. And as we read upwards to
downwards it in a particular vertical row it
decreases.
ELECTRONEGATIVITY
TREND
Factors influencing a Reaction

1- Inductive Effect

2-Mesomeric Effect

3-Electromeric Effect

4- Steric Effect
 INDUCTIVE EFFECT

“The effect of the sigma

electron displacement
towards the more
electronegative atom by
which one end becomes
positively charged and
the other end negatively
REASON OF INDUCTIVE EFFECT

 Its due to difference between

electronegativity of different atoms.

 The more electronegative will acquire

small /Partial negative charge.

 The less electronegative will acquires

a small /Partial positive charge
 Example
 In ethyl chloride, Cl is said to have an electron
withdrawing –I effect. ... Thus, the
substituents or functional groups can be
classified as electron-withdrawing (–I) and
electron-donating (+I) groups.
 Let us explain the inductive effect by
considering ethane and ethyl chloride as
examples. The C-C bond in ethane is non-polar
while the C-C bond in ethyl chloride is polar. ...
To compensate for it, the C1 draws the shared
pair of electrons between itself and C2 This
polarization effect is called the inductive effect.
Ehtyl chloride induction effect
 +I and –I effect
 -I effect means electro-attracting
 E.g. F , Cl , Br , I, OH.
 +I effect means electro-releasing.
 E.g. primary Alkyl, secondary Alkyl, tertiary

 Tertiary Alkyl exert more + I effect than

secondary exert more + I effect than primary
Alkyl.
 Inductive effect
transmission
 An inductive effect is not
confined to the
polarization of one bond it
is transmitted along a
chain of carbon atoms,
although it is insignificant
beyond the secondary
Explana
Application of inductive effect
 Effect on Bond Length: usually bond
length decreases with increase of
electronegativity

 Dipole Movement: As inductive effect

increases dipole movement increases.
 Strength of Acids: with increase in +I
removal of hydrogen becomes difficult so
decreased acidic strength.
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.4
Dated 04-02-
2022
 Todays topic

 Mesomeris

m
Factors influencing a Reaction

1- Inductive Effect

2-Mesomeric Effect

3-Electromeric Effect

4-Steric Effect
 MESOMERISM
(MESOMERIC EFFECT)
The mesomeric effect in chemistry is a
property of substituents or functional
groups in a chemical compound. It is
defined as the polarity produced in the
molecule by the interaction of two pi
bonds or between a pi bond and lone
pair of electrons present on an
adjacent atom.
 MESOMERIC EFFECT
 It involves π electrons of double and
tripple bonds.
 “ The mesomeric effect (M effect)
refers to polarity produced in a
molecule as a result of interaction
between two π bonds or a π bond
and a lone pair of electrons.”
 This effect is transmitted along a chain in
similar way as are in Inductive effect.
 IMPORTANCE
 The mesomeric effect is of great
importance in conjugated
compounds.

 CONJUGATED COMPOUNDS:
 Are the compounds in which
carbon atoms are linked
alternatively by single and
double bonds
 Explanation

 In such conjugated
system the π electrons
get delocalized as a
consequence of
mesomeric effect giving
a number of resonance
structure of the
 Mesomerism of carbonyl
 Consider a carbonyl group
the oxygen atom is more
electronegative than the
carbon atom. As a result, the
π electron of the carbon-
oxygen double bond is
displaced towards the
oxygen atoms this gives
Carbonyl Group
(mesomerism)
 Representation of mesomeric
effect
 The mesomeric effect is
represented by a curved arrow.
The head of the arrow resents the
movement of a pair of π electrons.
 If the carbonyl group is conjugated
to a carbon double bond, the
above shown polarity will be
transmitted via the π electrons
 Types of mesomerism

+M effect
Jus like inductive effect it is electron
withdrawal and release. The atom which
loses electron towards the carbon atom is
said to be have +M effect.

-M effect:
those atoms or group which draw
electron away from carbon atom are said to
have –M effect
+M effect
-M effect
Resonance
 Application of M effect
 Just like inductive effect it results in
permanent state of molecule
 It dose not depend any reagent
 The inductive and mesomeric effect
both indicate charge distribution in a
molecule
 So both effectively provide point of
attack for electrophile and
nucleophiles on a molecule.
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.5
Dated 07-02-
2022
 Todays topic

 Electromeric Effect

 Resonance Effect
Factors influencing a Reaction

1- Inductive Effect

2-Mesomeric Effect

3-Electromeric Effect

4-Steric Effect
 Electromeric Effect
 Like mesomeric effect it also
involves π electrons.
 It is also referred to as polarity in a
multiple bonded compounds
 It is expressed as E Effect.
 However it depends by reagent
unlike inductive and mesomeric
effect which are directed by
electronegativity.
 Reagent
 A reagent is a substance or
compound added to a system to
cause a chemical reaction, or added
to test if a reaction occurs. The
terms reactant and reagent are often
used interchangeably—however, a
reactant is more specifically a
substance consumed in the course
of a chemical reaction.
 Theory
 When a double or tripple
bond is exposed to a
electrophile E+ (a
reagent), the two π
electron which form pi
bonds are completely
transfer to one atom or to
Ethene electromeric effect
 Resonance Concept

 The representation
of a real structure
as a weighted
average of two or
two more forms is
called resonance.
 Lewis Structure
 When two or more Lewis
Structures can be written for a
compound, these structures are
called resonance contributing
structure or canonical Structure,
and the real structure is the
hybrid of these structures.
Canonical Structure
Benzene
 Energy in resonance
 The energy of actual molecule,
i.e resonance hybrid is less than
the contributing structure.
 The difference of energy
between the actual molecule
and the contributing structure of
the lowest energy is called the
resonance energy.
The rules of resonance
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.6
Dated 08-02-
2022
 Todays topic

Steric Effect
Factors influencing a Reaction

1- Inductive Effect

2-Mesomeric Effect

3-Electromeric Effect

4-Steric Effect
 General Concept
 Any effect on a molecule, a
reaction, etc. due to the size
of atoms or groups. Common
steric effects include steric
hindrance and van der Waals
repulsion. ... This is an example
of a steric effect caused by
steric hindrance: the tertiary
carbon is more hindered than
 Definition
 “Steric effects are nonbonding
interactions that influence the
shape and reactivity of ions
and molecules. Steric effects
complement electronic effects,
which dictate the shape and
reactivity of molecules.”
DIFFERENCE
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.7
Dated 09-02-
2022
 Todays topic

 HYPERCONJUGATION.
 Fission

When a bond breaks

two possibilities
1- homolytic fission
2- heterolytic fission
 Reaction Intermediates
 Hetrolytic and homolytic bond fission
results in formation of short lived
fragments called reaction
intermediates.
Among these include :
1- carbonium ions(hetrolytic)
2-carbanions(hetrolytic)
3-cabocations(hetrolytic)
4-carbon free radicals(homolytic)
 Carbonium ions
(carbocations)
 Carbocations is an organic
ion which contain positively
charged Carbon atom, also
called as carbonium ion.
 They are formed by
hetrolytic fission
Carbocation
Carbanions
Stability of carbonium ion
 The stability of
carbonium ion is
influenced by both
resonance and inductive
effect
Fission products
 BASIC CONCEPT
 The system of delocalzed electron
discussed so far involved only in
interaction of π electrons.
 Delocalization ofσ electrons is also
possible

 For compounds which have CH, CH2 and

CH3
group attached to a double bonded carbon
atom, the following types of contributing
structures can be written
 Hyper-Conjugation
 Hyper conjugation may be thought
as a special type of resonance or
mesomeric effect.

 The idea of hyperconjugation wa put

forward by Baker & Nathan in 1935.

 It is also called No-Bond Resonance.

 Definition
 “The conjugation of σ-bond
with a multiple bond or a π-
bond, i.e separation of a σ-
bond from a multiple bond or
a π-bond by only one single
bond also produces resonance,
such conjugation of σ-bond
with π-bond is termed as
Hyper-Conjugation.”
Types of Hyperconjugation

 1- C-H Hyper conjugation

carbon hydrogen bond is involved

 2- C-C Hyper conjugation

carbon carbon bond is involved

 C-C hyperconjugation
 Movement of Pi electrons through the p-
orbital pathway is Mesomeric effect and
leads to resonance.
Movement of sigma electrons through the
adjacent Pi system or a carbocation is
Hyper conjugation. It therefore involves
sigma electron delocalisation.
 Hyper conjugation
 Influence of hyper conjugation on the
structure
The C-C bond acquires some double bond
character and C=C acquires some single
bond character
C-H hyperconjugation
 Application
 Similar to resonance hyperconjugation is permanent
effect, and occurs even in ground state of the molecule.
 It also effects the physical properties of the compound i.e

 Shortening of bond
length.
 Effect on Stability
 Dipole movements
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.8
Dated 10-02-
2022
 Todays topic

 EFFECT OF STRUCTURE ON
REACTIVITY.
 Structure and Reactivity
 In the 19th century a
number of natural
products are isolated and
attempts are made to
correlate their
physiological activities
with their structure
 Pharmacophore Group
 Pharmacophore is defined as
“an ensemble of steric and
electronic features that is
necessary to ensure the optimal
supra-molecular interactions with
a specific biologic target and to
trigger (or block) its biologic
response.”
 Explanation
 Pharmacophore are a set of methods
related to SAR(Structure Activity
Relationship): they produce three-
dimensional arrangements of
functional group that are required for
activity. Pharmacophore are usually
used to derive relation between the
structure and the activity of a set of
molecules.
IUPAC Definition
 SAR
 Effect of unsaturation
 Effect of isomerism
 Effect of Alkyl groups
 Effect of size of Alkyl Group
 Effect of nitrile Group
 Effect of Hydroxyl Group
 Effect of Aldehydes and ketone Group
 Effect of Acidic Group
 Effect of Halogens
 Effect of Nitro and Nitrile Group
 Effect of Amino Group
 1-Effect of unsaturation
 Unsaturated compounds are found to be
more toxic than their corresponding
saturated compounds.
 It is noted that toxicity of compund
increases with unsaturation.
 E.g 1-propanol has mild norcotic property
than its corresponding allyl alcohol
 Example
 Incase of acrolein and crotonaldehyde
toxicity increases with unsaturation.

 Unsaturation also found to produce

toxicity in compounds other than carbon
 Eg arsenic compounds.
 2-effect of isomerism
a)Structural isomerism
Structural isomerism often show differences in their
physiological activities
e.g. o-hydroxy benzene is physiologically active,
while both p- and m- isomers are inactive.
b)Stereoisomerism
Both geometrical and optical isomerism show
differences in physiological activities.
e.g. maleic acid is poisonous while formic acid is
harmless
(-) Adrenaline is 12 times more active than(+) forms.
Similarly (-) Nicotine is twice as active as(+) forms.
 3-Effect of Alkyl Group
 Whenever an active hydrogen is
substituted by an alkyl group the
following observations are noted.

 Decrease in Biological Activity

 Increase in Toxicity.

 Appearance of masked properties.

.
 a) Biological Activity
In some compounds biological Activity decreases
by Alkylation
e.g. the convulsive property of Ammonia decreases
by introducing methyl groups i.e.
tri-methyl amine is free from all these effects
Similarly salicylic acid is more active than Methoxy
benzoic Acid
 b-Increase in toxicity
 In some compounds toxicity increases with on
Alkylation.
e.g. esters are more toxic than Alcohols
R-O-R, R-O-H
e.g. resorcinol dimethyl is more toxic than
resorcinol

e.g, theobromine and caffeine are much more

toxic than parent compound i.e, Xanthine
 c – Appearance of masked
property
 Some times alkylation leads to
appearance of a masked property
 cocaine is strong anesthetic than its inert
analogue
 Antipyrine is strong antipyretic while its
analogue having one methyl group is
inert
 4-Effect of Size of Alkyl Groups
 The size of alkyl group show maked effect on
the pharmacological activity.
e.g diethyl ether is stronger hypnotic than
acetone.

When methyl group of acetophenone is replaced

by ethyl group resulting compound is more
hypnotic.
 4- effect of Nitrile(-CN)
Group
 The parent compound of nitrile
group is HCN, which is well known
poison
 The introduction of nitrile group
may give rise to series of
compounds , the nitrile RCN and
isonitrile RCNR both are poisonous
 In inorganic chemistry cyanide ion
also exert poisonous effect.
 5-Effect of Hydroxyl Group

 A) weakens physiological activity

 B) loss of a particular Activity

 C)Increase in physiological
Activity
 a)Weakens the physiological
effect
 The introduction of hydroxyl group into
aliphatic compound weakens its
physiological activity. This weakening has
been found roughly proportional to the
number of hydroxyl group
 n-propanol is more active than glycerol

 Hexanol is more active than sorbitol

 b)Loss of a particular
Activity
 Sometimes the presence of
hydroxy group makes the
compound to lose its
particular activity. For
example
 Hydroxy caffeine has none
of the effect as that of
caffeine
 c) Increase in Physiological
Activity
 In case of aromatic compounds, the
introduction of hydroxyl group increases the
physiological Activity of the compound i.e
reverse as in case of aliphatic compounds.
 E.g. phenol is more toxic and strong
antiseptic than benzene
 Salicylic acid is more strong anti-fungal but
also anti rheumatic agent than bezoic acid
 Exception: introduction of more hydroxyl
groups in aromatic compound may lead to
toxicity i.e resorcinol more toxic than phenol
 6)Effect of Aldehyde and
Ketone
1-ALDEHYDE
Aldehydes are more reactive than ketone also
exhibit more biological activity. Higher groups with
Alkyl groups on Aldehyde may have combined
effects of alkyl and Aldehyde
2-KETONES
In general ketones possess narcotic effect. Aliphatic
ketone due to presence of alkyl group hypnotic
action is masked
Mixed ketones like acetophenone strong hypnotic
effect
While unsaturated ketones are diuretics.
 7) Effect of Acidic Group
 The introduction of acidic group such as –
SO3H, and –COOH in a molecule either
decrease or completely destroys the
physiological activity of the parent
compound.
 E.g. phenol is poisonous but benzene
sulphonic acid is harmless
 Nitro-benzene is poisonous but nitro
benzoic acid is harmless
 Amines are toxic but Amine acid is food-
stuffs
 8-Effect of Halogens
 The introduction of halogens are
used to increase useful as well
as well as toxic properties, but
at different states.
 Halogenation increase toxicity
only to a little extent but are
used to increase the activity.
 On the other hand positive
halogens decrease the toxicity
 9-Effect of Nitro(NO2) and
Nitrite(ONO)
1-NITRO GROUP (R-NO2)
The introduction of nitro to aan aromatic
compound increases its toxicity
e.g. Nitrobenzene, nitronaphthol.
2-NITRITE GROUP (R-ONO)
Nitrite group is isomeric with nitro group but
differs in action
e.g.aliphatic nitrites have dilating effect on blood
vessels and decrease blood pressure while nitro-
compounds have no effect.
 10-Effect of Amino Group
 In general the amino group is
toxic. Successive alkylation of
amino group decreases its toxicity.
 While acylation of amino group
decreases its physiological activity
 E.g. aniline is toxic while
acetanilide is as febrifuge.
P Pharmaceutical Chemistry-1
(Organic Chemistry)

Lecture No.9
Dated 11-02-
2022
Todays topic

 AROMATICITY.
 AROMATICITY
 It is the property of aromatic
compounds as the name indicates.
 it is property of conjugated
cycloalkanes.
 In which stabilization of molecule
is enhanced by π-electrons
delocalization.
 Act as frame work to create planer
molecule.
 Definition
 Aromaticity is a property of
conjugated cycloalkenes in
which the stabilization of the
molecule is enhanced due to
the ability of the electrons in
the π orbitals to delocalize.
This act as a framework to
create a planar molecule
Explanation
Explanation
 Huckel’s Rule
 a cyclic ring molecule follows
Hückel's rule when the number
of its π-electrons equals 4n + 2
where n is a non-negative
integer, although clearcut
examples are really only
established for values of n = 0 up
to about n = 6
 Criteria
 Aromatic compounds are more stable than theoretically
predicted using hydrogenation data of simple alkenes; the
additional stability is due to the delocalized cloud of electrons,
called resonance energy. Criteria for simple aromatics are:
1. the molecule must have 4n + 2 (a so-called "Hückel number") π
electrons[7] (2, 6, 10, ...) in a conjugated system of p orbitals
(usually on sp2-hybridized atoms, but sometimes sp-
hybridized);
2. the molecule must be (close to) planar (p orbitals must be
roughly parallel and able to interact, implicit in the requirement
for conjugation);
3. the molecule must be cyclic (as opposed to linear);
4. the molecule must have a continuous ring of p atomic orbitals
(there cannot be any sp3 atoms in the ring, nor do exocyclic p
orbitals count).
 Application

 Vital role in Bio-Chemistry.

 3 of 20 amino acids are aromatic.

 All five nucleotides that make

DNA and RNA sequence required
are Aromatic.