Stereochemistry

 Stereochemistry is the study of the three dimensional

shape of molecules and the effects of shape upon the
properties of molecules.
 Example :
CH3-CH2-CH2-CH3
n-Butane (C4H10) Iso butane
C4H10
 Isomers are compounds that have the same molecular
formulas but different structural arrangements of
atoms.

CH3-CH2-CH2-CH3
n-Butane (C4H10) Iso butane
C4H10

They fall into two categories: Constitutional isomers

and stereo isomers.
 Constitutional isomers are isomers that have different
atomic connectivity.
 Constitutional isomers are isomers that have different
atomic connectivity.
Examples: of constitutional isomers include butane
and isobutane (both have the molecular formula C4H10,

CH3-CH2-CH2-CH3
n-Butane (C4H10)
Iso butane
C4H10

but different structures and ethanol and dimethyl ether

(both have the formula C2H6O, but again the two differ
structurally.
CH3 -CH2-OH CH3-O-CH3
Ethanol Dimethyl ether
 Stereo isomers are isomers whose constituent atoms
are connected in the same sequence, but in different
spatial patterns.
A molecule can have more than one stereogenic carbon.
The number of stereoisomers can be determined by the 2n
rule, S)-(+)-lactic acid (left) and (R)-(–)-lactic acid
 where n equals the number of stereogenic carbons.
Thus, if one stereogenic carbon is present, there are two
possible stereoisomers;
 with two stereogenic carbons, there are four possible stereoisomers
Stereo isomers can be further subdivided into: enantiomers
and diastereomers.
Structural Isomers
1. Chain Isomers: Structures having a similar molecular
formula but differ in arrangement of carbon chain are
known as chain isomer.

CH3-CH2-CH2-CH3
n-Butane (C4H10)
Positional Isomers: Structures having a similar
molecular formula but differ in position of functional group
are known as positional isomers

CH3-CH2-CH2-CH2-Br
1-Bromo butane ( C4H9 Br)
2-Bromo butane ( C4H9 Br)
Functional Isomers: Structures having a similar molecular
formula but differ in functional group are known as functional
isomer

CH3 -CH2-OH CH3-O-CH3

Ethanol Dimethyl ether

Metamerism: Unequal distribution of carbon chain on either side of

functional group is known as Metamerism

CH2-O-CH2-CH2-CH3
Methyl propyl ether C4H10 O
Diethyl ether C4H10 O
Tautomerism: The existence of two or more chemical
compounds that are capable of facile interconversion
is known as Tautomerism.

Keto Enol
Optical isomer (d and l)
 Optically active compound: A compound which rotates
the plane polarized light is known as optically active compound.
 Chiral compounds are optically active; they rotate the
plane of polarized light.
 Achiral compounds do not rotate the plane of polarized
light. They are optically inactive.
 If the compound rotates the plane polarized light to the
right side, then it known as Dextrorotatory compound.
[d or (+)].
 If the compound rotates the plane polarized light to
left side, then it known as laevorotatory compound.
[l or (–)].
 Ordinary light is converted into plane polarized light by Nicol prism
(Polarizer), and it is made up of calcite crystals or crystalline CaCO3.

 Light Source: D-line Sodium lamp at λ = 5830 A0

 A polarizer measures the degree of optical rotation of
a compound

 T is the temp in °C
 l is the wavelength
 a is the measured rotation in degrees
 l is the path length in decimeters
c is the concentration in grams per mL
Each optically active compound has a characteristic
specific rotation
Optical Purity = Observed Specific rotation/Specific
rotation of pure enantiomer
Enantiomer Excess = Excess of a single = specific rotation
enantiomer/Entire mixture

 Racemic mixture, which contains an equal amount

(equi-molar mixture) of the two enantiomers, is optically
inactive
Cahn-Ingold-Prelog (CIP system)–R/S Notation
The Cahn-Ingold-Prelog R/S rules are used for naming
enantiomers and diastereomers.
1. Identify the chiral centres (most commonly an sp3 C
with 4 different groups attached)
2. Assign the priority to each group (high = 1, low = 4)
based on atomic number of the atom attached to the
chiral center (remember the first point of difference
rule)
3. Position the lowest priority group away from you as if
you were looking along the C-(4) s bond.
4. For the other 3 groups, determine the direction of high
to low priority (1 to 3)
5. If this is clockwise, then the center is R. (Latin: rectus
= right)
6. If this is counter clockwise, then it is S. (Latin: sinister
= left)
Example: Chlorofluoroiodomethane
 The chirality center is easy to spot, and the four attached
groups are I, Br, F and H listed in priority order, highest to to lowest.
Cahn-Ingold-Prelog (CIP system)–R/S Notation

Sequence Rules

1give priority to high atomic number higher atomic number get high priority

S-configuration
In case of isotopes higher the atomic mass higher the priority

S-configuration
If the priority is not assigned based on atomic number (or ) atomic mass of the first atom then
consider the substituted atom ?next set & unit it is assigned

S-configuration
Rule 4: If Aromatic system (or) Triple bond (or) double bond atoms are present the order of
priority as follows
Rule-5

The order of priority for most common groups & atoms are as follows

- - - -
Naming from the Fischer projection

Rank the groups (or atom) that are bonded to the

asymmetric carbon and draw an arrow with the highest
priority to the lowest priority.
2. If the lowest priority is on a horizontal bond, the naming
is opposite to the direction of the arrow.
The arrow can go from group 1 to 2, passing group 4,
but not group 3

1
-Lactic acid
4. A Fischer projection can only be rotated 180° in the
plane of the paper to yield the same molecule.
Relative configuration (D/L configuration)

-OH group is right side to CH2OH So,

D-Glyceraldehyde is relative
Configuration

D-Glyceraldehyde

OH Group Present Right Side It

Is Called D Type
L-Glyceraldehyde

Relative configuration has been seen in protein,

carbohydrate
and alkaloids.

OH group is left side to CH2OH

So, L-Glyceraldehyde is relative
Configuration
Geometrical isomer:
 Also Cis-trans isomerism
 Isomerism having same molecular formula different in position of functional group
around double bonded in space

Geometrical isomerism shown by

Alkenes C=C
Oxines C=N-OH
Azo

It exhibits geometrical isomer because of restriction of bond rotation of bonds

They differ in the physical and chemical properties because of geometrical isomerism

Cis form is les than the trans form because of steric hindrance and bulky groups

The isomer is converted into trans (or) vice versa only if those isomers are heated to higher
temperature
Cis-Trans system

Cis means two similar groups are on same side

Trans means two similar groups are on opposite

direction.
 Trans isomer is more stable than Cis isomer due to
steric hindrance is more with cis isomer because two
bulky groups are in same side.
 Trans isomer having Dipole moment μ = 0

Cis Isomers
Trans isomer
E/Z system: In alkenes, if carbon is attached with four
different groups than it will be nomenclatured by E/Z
system.
 E means Entegegen-Opposite side
 Z means Zusammen-Same side

E isomer because two Z isomer because two

prior group are on prior group are on
opposite side Same side
Enantiomer and Diastereomers
Enantiomer The stereoisomer of compounds which are
non-superimposable mirror image of each other are known
as enantiomers.
 Enantiomers are often referred as a optical isomer.
 Chirality is necessary and sufficient condition for
existence of an enantiomer.
 Non-superimposabilty on its mirror image is necessary A
and sufficient condition for existence of enantiomerism.
 It is also a necessary but not sufficient condition for
optical activity

E.g., Racemic mixture is optically inactive.

 All enantiomer have similar physical property
(exception is specific rotation) while different chemical
B
property.
A B C

A and B and C and D are pair of enantiomer

 While A and C, A and D, B and C and B and D are pair
of diastereomer.
Diastereomer: The stereoisomer of compound which
are not mirror image of each other are known as diastereomers.
 All diastereomers have similar chemical property and
different physical property.
 Diastereomer is possible if the molecule is having two
or more than two chiral centre.
Meso compounds: These are the ones which are superimposable
on their mirror image even though they contain
chiral carbon. Because it has a plane of symmetry in its
structure, so it is optically inactive
These are the ones which are superimposable
on their mirror image even though they contain
chiral carbon
Erythro/Threo
Erythro: If two similar groups are on the same side of
carbon chain.
Threo: If two similar groups are on the opposite side of
carbon chain

L-Erythro

D-Erythro
Threo: If two similar groups are on the opposite side of
carbon chain

L-Threo
D-Threo
Epimer When two diastereomers differ in the stereochemistry
at only one stereocentre then these are epimers of each
other.
E.g., Glucose and galactose are epimer at C-4
 Glucose and mannose are epimer at C-2 16 isomers of glucose
Anomer If diastereomers differ in their configuration at C-1 (anomeric carbon), then these
are called anomers.

 β-anomer: If –OH group is in upward direction to anomeric

carbon.
 α-anomer: If –OH group is in downward direction to
anomeric carbon
Saytezeff’s rule & Hoffman's rule

Orientation of product formed by E1 &E2 reactions is based on

two rules

Saytezeff’s rule

More stable yields 80%

1 Less stable yields 20%

2
Hoffman's rule
Markonikov’s Rule
When an acidic reagent is added to –C=C-than the positive
portion of reagent goes to the side of double bond or triple
bond contain more H.

1° CARBOCATION

2° CARBOCATION
So according to the rule, 2° carbocation can easily
formed compared to 1° carbocation.
Reactive Intermediate in Organic Chemistry

Carbocation/Carbenium ion Carbon having positive

charge is known as Carbocation

General structure
of carbocation

Stability of Carbocation 3° > 2° > 1° > Methylcation

 > > >

1°
3° 2°

Methylcation

 Because of 3° Carbocation can easily form so it is more

stable than 2° and 1°.
 3° Carbocation directly attached with three partially
electron donating alkyl group. So it will increase the
stability of Carbocation.
Stability Of Carboanion

If the number of alkyl groups (or) methyl groups increases on

anionic carbon atom the –ve charge is also increase on the carbon
& consequently decrease the stability

In stability of carbo cations we have

Inductive effect
Conjugative effects are involved
Stability Of Free Radicals

The stability of carbo radical degeneration of delocalization of odd electron

1)Hyper conjugate
2)Conjugation resonance effect involved in the stability of alkyl radicals
EDG donate the electron to cationic carbon and increase
the stablity of it.
 EDG withdraws the electron and destabilizes carbocation,
decrease its stability

Classical Carbocation: +ve charge located on one carbon

atom/delocalized by resonance involving unshared pair
of electrons
Carbanions: It contains an unshared pair of electrons or
negative charge is known as carbanion. Therefore it acts as
base/nucleophile

General Structure
of carbanion

Stability of Carbanions: 1° > 2° > 3°

 Stability of Carbanions: 1° > 2° > 3°
Effect of electron donating/withdrawing group on carbanion

 Stability of carbanion increase by

 When carbanion carbon conjugated with –C=O, –C=N etc.
Carbanion increases its stability with an increase in the
amount of s character at carbanion carbon.
 Carbanion is stabilized by sulphur/phosphorus atom
due to pπ-dπ bonding
Carbene Carbon having open sextet is known as carbene
or divalent carbon is known as carbene.
 Carbene are very reactive species. In an element of a compound,
 Unshared pair of es. when the number of electrons
General Structure of carbene in the valence shell is equal to
6, it is called sextet of electrons.

In carbene, these two electrons are paired or unpaired

Singlet carbene: Two non-bonding electrons are in
paired, present in SP2 hybridized orbitals

Triplet carbine: Electrons are unpaired one electron present

in SP2 hybridized orbitals and other presents in vacant
unhybridized p-orbital.
Hybridization

Hybridization involves the following steps

1. Formation of Excited State: Paired electrons jump
to higher energy levels to create, if necessary, more
Milk and
number of half-filled orbitals. sugar is a
mixture
2. Mixingand Recasting of Atomic Orbitals: Orbitals
of valence shell mix to form new set of atomic orbitals
having same energy. The new orbitals then formed are
called hybrid orbitals.

Need for the concept of hybridization

 To explain valencies of element.
 To explain equivalence of bonds.
 To explain geometry of molecule
Types of Hybridization
 Sp3-Hybridization: Mixing and recasting of ’s’
orbitals with three ‘p’ orbital of same atom forming four
identical orbitals tetrahedral arranged in space.

 Sp2-Hybridization: One’s’ and two ‘p’ orbitals of the

same atom mix and form three identical orbitals trigonally
arranged in space.
 Sp-Hybridization: One’s’ and one ‘p’ orbital of the
same atom mix and form two identical orbitals diagonally
arranged in space
Examples:
In the case of methane, the three 2p orbitals of the carbon
atom are combined with its 2s orbital to form four new
orbitals called “sp3” hybrid orbitals. The name is simply a
tally of all the orbitals that were blended together to form
these new hybrid orbitals. Four hybrid orbitals were required
since there are four atoms attached to the central carbon
atom. These new orbitals will have energy slightly above
the 2s orbital and below the 2p orbitals as shown in the
following illustration. Notice that no change occurs with the
1s orbital
 These hybrid orbitals have 75 per cent p-character and
 25 per cent s-character which gives them a shape that is shorter
and fatter than a p-orbital.
In the case of ammonia, the three 2p orbitals of the
nitrogen atom are combined with the 2s orbital to form
four sp3 hybrid orbitals. The non-bonded electron pair will
occupy a hybrid orbital.

A stick and wedge drawing of ammonia showing the

non-bonding electrons in a probability area for the hybrid
orbital.
In the case of water, the three 2p orbitals of the
oxygen atom are combined with the 2s orbital to form four
sp3 hybrid orbitals. The two non-bonded electron pairs will
occupy hybrid orbitals.
In the boron tri-fluoride molecule, only three groups
are arranged around the central boron atom.
In this case, the
2s orbital is combined with only two of the 2p orbitals
The trigonal
planar arrangement has bond angles of 120.

Forming three hybrid orbitals called sp2 hybrid orbitals

In this case, the
2s orbital is combined with only two of the 2p orbitals (since
we only need three hybrid orbitals for the three groups
 In the beryllium dichloride Molecule since only two
groups are attached to beryllium,
 we only will have two hybrid orbitals.
 In this case, the 2s orbital is combined with only
one of the 2p orbitals to yield two sp hybrid orbitals.
 The two hybrid orbitals will be arranged as far apart as possible
from each other with the result being a linear arrangement.
.
Hybridization involving d-orbitals
Some 3rd row and larger elements can accommodate more
than eight electrons around the central atom. These atoms
will
also be hybridized and have very specific arrangements of
the attached groups in space. The two types of
hybridization involved with d orbitals are sp3d and sp3d2.
The groups will be arranged in a trigonal bipyramidal
arrangement with sp3d hybridization...bond angles will be
Atomic Structure
Structure of an Atom

An atom consists of negatively charged electrons, positively

charged protons, and neutral neutrons.
 Atomic number: numbers of protons in its nucleus
(E.g., 6C, 7N, 8O)
 Mass number: the sum of number of protons and neutrons
in a atom (E.g., 12 6C, 14 7N)
 Isotopes have the same atomic number but different
mass numbers
Isotopes are chemically same and physically different.

Isobars are atoms of different elements

having the same atomic mass but different atomic
number.
 That is, isobars are
elements which are chemically different but physically same
 their number of electrons is different, their chemical
properties are different. Examples of isobars are Fe58
and Ni58.
Isotones
Isotones are elements having the same number of
neutrons. Examples of isotones are Chlorine-37
and Potassium-39. Both have 20 neutrons in their
nuclei.

The atomic weight: The average weighted mass of

its atoms
 Molecular weight: The sum of the atomic weights of all
the atoms in the molecule.
Distribution of electrons in an atom
 The atomic orbital closer to the nucleus has the lowest
energy.
 Degenerate orbital's have the same energy.
Rules for determining electronic
configuration
The Aufbau principle Electrons occupy the orbital
with the lowest energy orbital first.
E.g., 10
5B-1S and 2S orbital first filled than one electrons
go with 2Px orbitals
The Pauli exclusion principle Only two electrons can
occupy one atomic orbital and the two electrons have opposite
spin
Hund’s rule Electrons will occupy empty degenerated
orbitals before pairing up in the same orbital.
Bonding and Hybridization
Bond In a molecule, the atoms are held together by a strong force
of attraction to form a bond. The force of attraction may be
due to oppositely charged ions or due to orbital overlap.

Types of bonds
Three different types of bonds are formed depending on the
electropositive or electronegative character of atoms involved.
a. Electropositive element + electronegative element =
Ionic Bond
b. Electropositive element + Electropositive element =
Metallic bond
c. Electronegative element + electronegative element =
Covalent bond
Ionic compounds are formed when an electropositive element
transfers electron (s) to an electronegative element or
transfer of valance shell electron.
E.g., Na+ and Cl–, In which Na+ having one electron in its
outer orital while Cl– having 7 electon in its outer shell so, Na+
donate its valance shell electron to Cl– to complete the Octet.
Covalent Compound:
Mutual sharing of electrons: non-polar covalent bond (e.g., H2)
Co-ordinate covalent Bond:
It is a bond formed due to transfer of electron pair from one
atom to other.
Electronegativity of an atom
 It depends upon Atomic number and atomic radius of
an atom.
 Any atom having more atomic number and lower atomic
radius is more electronegative than other atom.
Polar bond
A polar bond has a negative end and a positive end (E.g.,

C+δ—Cl-δ).

Non-polar bond A bond which is made up by same

charged atom is known as non-polar bond. ( H-H, C-C)

Dipole moment It depends upon:

1. Molecule having more than one dipole
2. If centre of negatively charged does not concide with In chemistry, a formal charge (F.C. or q)
is the charge assigned to an atom in a
centre of positively charged.
molecule, assuming that electrons in all
Dipole moment (D) = μ = e x d chemical bonds are shared equally
Where, e is magnitude of the charge on the atom measured between atoms, regardless of relative
in e.s.u (electron spin unit), d is distance between the electronegativity.
two charges (in cm), μ is dipole moment of molecule
(Debye unit)
Formal charge = number of valence electrons–(number
of lone pair electrons +1/2 number of bonding electrons
Octet rule
During bond formation, the atoms gain, lose or share
electrons so that the outermost or valence shell of an atom
has eight electrons as in inert gases.
Electronic Theory
Put forth by Kossel and Lewis in 1916. The main postulates
are
 Valence shell electrons take part in bond formation.
 Inert gases have stable outermost configuration.
 Elements tend to acquire inert gas configuration by
gaining or losing electrons. On this basis, Ionic and
Covalent bonds are explained
 Ionic Bond: Bonds formed by gaining or losing electrons
in which the ions formed are held together by
electrostatic force of attraction.

Limitations of octet rule

 It fails to explain formation of compounds with incomplete
and expanded octets.
 It fails to explain about nature of forces responsible for
the combination of atoms.
 It does not explain energy, stability and reactivity of
molecule.
 It does not explain geometry and shape of different
molecules.
Exceptions to the octet rule
 Elements in groups IA, IIA and IIIA do not follow the octet
rule.
 Electron-dot formula for BF3, the boron will not have
eight electrons.

 A surprising element in this group is the inert gas, xenon.

If xenon is exposed to fluorine gas in the presence of
light for several weeks, it can form XeF2, a colourless
crystalline
solid.
Aromatic carbocyclic compounds
Benzene
 A planar molecule has six identical carbon–carbon bonds.
 Each π electron is shared by all six carbons.
 The π electrons are delocalized.
Rules for drawing resonance contributors

Only electrons move.

 Only p electrons and lone-pair electrons move.
 The total number of electrons in the molecule does not
change.
 The numbers of paired and unpaired electrons do not
change.
The electrons can be moved in one of the following
ways
General mechanism for electrophilic aromatic
substitution of benzene
Step 1: It is a slow step and hence a rate
determining step
 Intermediate is arenium ion or benzonium ion or wheland
intermediates
 Reactivity of EAS
 EDG on benzene ring increases the reactivity towards
electrophillic aromatic substitution.
 EWG on benzene ring decreases the reactivity towards
electrophilic aromatic substitution. e.g., of reactivity order
List of electron donating and withdrawing groups
Ortho-Para
Directing

No one is reactive -R
Weakly activating
Ar
-CH=CH2
-NHCOR
NH2 -OR
NHR NR2 -OH -OCOR Moderately activating

Strongly activating
Moderately deactivating
Standard of comparision -H Weakly deactivating CHO
Deactivating Substituents
(EWG)
Strongly COOH
Scan deactivating
COOR
NO2 COR
NR3
SO3H CN -COCl
Nomenclature of Hetrocyclic Compounds

Hetero atom Valence 2 elections

Hetero atom Valence 3 elections
Oats
PAN
Oxa
Thia Selena
Tellura
O Phospha
S Te Se Arsa Aza
As
P 3
N
3
Hetero atom Valence 4 elections
Germa Sila
Ge Si
 Azete
pyrrole

pyridine

Azepine

Azocine
oxirene
oxete

(Oxole)

furan
oxin
Heterocyclic Chemistry: Structure and
Property
Heterocyclic compounds are organic compounds that
contain a ring structure containing atoms in addition
to carbon, such as sulfur, oxygen or nitrogen, as the heteroatom.
Carbocyclic compounds are organic compounds that
contain ring system made up entirely of carbon atoms
p-Excessive heterocyclic system have an e - –

donating heteroatom
a heteroatom donates a pair of p-electrons to the p-system
(pyrrole, thiophene, furan)
Five member ring containing O, NH, S are p-Excessive
system because of in ring system total six electron are
distributed
in only five atom so each atom having a more than
one electron that’s why it is p-Excessive heterocyclic system.
p-Deficient heterocyclic have an e– - accepting heteroatom eg. N or N+

Six member ring system has N atom is an example of p-

Deficient heterocyclic system due to electronegativity of N

atom is more compare to carbon so electron density is more

at N atom so each carbon has less one electron that’s why it
is p-Deficient heterocyclic system.

Towards SEAR reaction: Pyrrole > Benzene > Pyridin

Heterocyclic Compounds and Benzene:
A Comparison
 Both are aromatic because it obeys 4n + 2 p e Hückel’s
rule.
 Delocalization gives rise to resonance resulting in
stability of compounds, benzene is more stable than
heterocyclic compounds.
 Both undergo electrophilic as well as nucleophilic
substitution.
 Reactions are regioselective
Five member heterocyclic ring system contains one
hetero atom; Pyrrole, Furan and Thiophene

All are aromatic: Thus, 6p electrons

 Sp2 hybridised and planar
 Lone pair electrons on hetero atom is in p-orbital so it
is overlaps with the carbon p-orbital
 Thus, electrophilic aromatic substitution is easy.
 Nucleophilic Substitution is Difficult
Structure of Pyrrole
 It having a 6p electrons, conjugated system and delocalization
of p electron takes place.
 Overlapping p orbital.
 In pyrrole, each of the 4-C contribute 1p electron and
the sp2hybdridised nitrogen contributes 2 e that’s why
obey the 4n + 2 p e Hückel’s rule.
 Lone pair electrons on nitrogen atom are in p-orbital so
it is overlaps with the carbon p-orbital.
 Electron movement thus results in resonance.
 Lone pair on N a part of aromatic sextet.
Basicity and Reactvity of Pyyrole
 Lone pair on N-atom is part of aromatic sextet,
therefore, less available for bonding with acids. Thus
Pyyrole - less basic, less Nucleophilic than aliphatic amines. Weakly basic but has
greater aromatic character
 Electron pair NOT available to act as base.
Electrophilic aromatic substitution reaction in pyrrole

 In pyrrole, Electrophilic aromatic substitution reaction

occurs at C-2 position because of it having more no of resonating
structure compare to attack of electrophile at C-3 of pyrrole
ring, and the positive charge in accommodate in three atom
rather than two atom, if attack of electrophile occur at C-3.
Same like pyrrole in furan and thiophene EAS reaction
takes place on C-2.
 Other Properties of Pyrrole
Pyrrole having more boiling point than furan and thiophene,
because of in pyrrole structure inter molecular hydrogen
bonding takes place due to the N-H group in ring system.
Due to intermolecular H-bonding pyrrole has more b.p than
furan and thiophene
Pyrrole and Furan Is Least Aromatic Than Thiophene
Because of electronegativity of sulphur in less than O and N
containing heterocycles (Furan and Pyrrole) so it can easily
delocalized electron in ring system that’s why thiophene is
more aromatic than pyrrole and furan
Six Member Heterocyclic System: Pyridine
 Aromatic
 Pyridine replaces the CH of benzene by a N atom
and a pair of electrons)
 Flat planner molecule with bond angle 120 (SP2
Hybridization with similar resonance stabilization
energy
 Lone pair of electrons not involved in aromaticity
like pyrrole
It undergoes Substitution reaction rather than addition
reaction.
 The molecule has a dipole moment as the e– -
distribution is uneven.

The C-C bond lengths > the C-N bond lengths

Basicity of Pyridine
Pyridine is more basic than pyrrole because of Kb of
pyridine is 2.3 × 10–9 and Kb of pyrrole is 2.5 × 10–14.
Pyridine has more Kb value than pyrrole, so more
basic.
 Another reason to more basicity of pyridine is, in
pyrrole the lone pair on N atom is involved in
aromaticity while in pyridine it is not a case
Electrophilic Aromatic Substitution Reaction in
Pyridine
 Pyridine is highly deactivating ring because of p-
Deficient heterocyclic system.
 EAS reaction is least readily than benzene, because of
N is more electronegative than C and is a net acceptor
of p-density and so makes the p-cloud less available.
 In other words, N deactivates the ring, especially in
positions 2 and 4.
 So electrophilic aromatic substitution (EAS) reaction
occur at C-3 position.
In the below figure it is clearly shown that in pyridine
the positive charge is generate at C-2 and C-4 that’s
why EAS reaction is not possible on it so EAS reaction
is possible on C-3 only because there is no any positive
charge generate on C-3.
 Nucleophilic Aromatic Substitution reaction occurs at
C-2 and C-4 , because of positive charge is generate at C-2 and C-4 so
neucleophile can easily attack on electron
deficient center
 Fused Heterocycles
eg. Indole, Benzofuran and Benzothiophene

 It is a fusion of benzene and pyrrole ring it is also

known as banzopyrrole.
 Aromatic because cyclic conjugated, planar
 Aromatic due to 10 p-electrons and obey Huckel’s rule
(8p-electrons from the double bond and 2p-electrons
from the hetero atom) lone pair of e from N delocalizes
to give the aromatic character
 Benzene part of indole is non-reactive.
 Electrophilic aromatic substitution occurs at the
3-position because of more canonical structures are
form if attack occur at C-3 position compare to attack
of electrophile at C-2.
Analogous compounds derived by fusion of a benzene
ring to a pyrrole, furan or thiophene nucleus called
indole, benzofuran and benzothiophene.
 For all analogues: Rings numbered in a way that it gives
lowest possible number to the heteroatom
It is also known as benzopyridine: due to fusion of one
benzene and one pyridine ring
 Aromatic because cyclic conjugated, planar
 Aromatic due to 10 p-electrons and obey Huckel’s
rule.
 Electrophilic subsitution in quinoline and isoquinoline:
explanation
Electrophilic aromatic substitution occurs at the benzene
ring giving a mixture of substitution products – C-5 and
C-8
Nucleophilic aromatic substitution occurs at the pyridine
ring giving substitution at C-2 and C-4 for quinoline
and C-1 for isoquinoline
Nucleophilic substitution reaction occurs at C-2 and
C-4 position same like pyridine.
 Explain by looking at the anionic intermediates
 Hydride can be displaced at the 2- and 4- positions
 Stable intermediate from attack at position 2- and 4-,
negative charge on nitrogen atom
Purines and Pyrimidines
 Most important heterocyclic ring system from biological
point of view, nucleic acids
 Pyrimidine: Contains 2 pyridine-like N in a 6-membered
aromatic system
 Purine: Contains 4 N in a fused ring system, 3 of these N
are basic and pyridine-like with their l.p. e in sp2 orbitals
in the plane of the ring while remaining 1 N is nonbasic
and pyrrole-like with l.p. e as part of aromatic p e system.
 Replacing a CH group in the pyrrole ring with a
nitrogen atom can give rise to two compounds: pyrazole
and imdazole
 Only one nitrogen atom can contribute two electrons to
the aromatic sextet.
 It is the nitrogen with the hydrogen and
it is described as pyrrole-like nitrogen. While the second
nitrogen (2nd position) which has no hydrogen is described as
pyridine-like.

 The lone pair on pyrrole-like nitrogen is delocalized round

the ring while that on the pyridine-like nitrogen is localized in
sp2 orbital on nitrogen. Thus these compounds have properties
intermediate between those of pyrrole and pyridine.
Physical Properties of Imidazole and Pyrazole
Solubility
 Imidazole and pyrazole are water soluble solids and
insoluble in aprotic solvent.
 They have very much higher boiling point:256 and
187 °C respectively, this difference is due to imidazole
has an extensive hydrogen bonding than pyrazole
 Thus imidazole molecules can exist as oligommers, consequently
more energy is required to break these bonds to bring the molecules from
one phase to another.
 On the other hand pyrazole molecules can form dimers
only thus lesser energy is required to break these
molecules.
 N-subsituted imidazole and pyrazole have lower boiling
and melting points than the unsubstituted compounds
due to inability to form H-bonds.
Basicity
Imidazole is a stronger base than pyrazole or pyridine and
of course pyrrole. Thus imidazole and pyrazole are more
stabilized than pyrrole in acidic medium.
Basicity order: Imidazole > Pyrazole > Pyridine >
Pyrrole
This can be explained as follows

 Pyrrole is not basic because the lone pair on the only

nitrogen is needed to complete the aromatic pi system and
 protonation if occurs at all occurs at carbon rather than on
nitrogen and the resulting cation is not aromatic
 Both of imidazole and pyrazole have two nitrogen
atoms and on protonation the positive charge can be
delocalized
over them. However, pyrazoles are much weaker bases

 than imidazoles. This difference is due to the fact that the

positive charge in pyarzolium ion is less delocalized than in
the imidazolium ion.
Effect of substitution on basicity
 Generally E.D.G groups on the ring increase the basicity
while E.W.G. decrease it.
 N-methyl imidazole is more basic than imidazole itself.
 However, N-methylpyrazole is less basic than pyrazole
which can be attributed to steric hindrance effect which
cause difficulty in accessing the lone pair of electron
by the proton.
 Diazoles are less reactive than 5-membered heterocycles
with one heteroatom (pyrrole and its analogs) in
electrophilic aromatic substitution due to the inductive
electron-withdrawing effect of the second heteroatom.
 However, they are more reactive than pyridine due to
delocalization of the lone pair of electrons on the Natom
make the C- atoms bear negative charges while
in pyridine the N- atom exerts inductive electron withdrawing
effect only.
 The orientation in pyrazole, is at the 4-position due to
the deactivation effect of the pyridine-like nitrogen
 The orientation in imidazole, is at 5-position, due to the
additional N-atom deactivates its vicinal positions
 However, if the position 5 is occupied the electrophiles
will be directed to 4-position.
Conformation :Different three dimensional arrangements of atoms
results due to free rotation about C-C single bond, this is known as
conformation

Anti: It is a type of staggered

conformation dihedral angle
between two bulky groups is 180°.

Gauche: It is a type of staggered

conformation dihedral
angle between two bulky groups is
60°.

Staggered forms are more stable than eclipsed because

all atoms are arranged opposite to each other so it reduces
steric hindrance among them
Conformation In Cyclohexane

Chair conformation > Twist boat conformation > boat conformation >half chair
conformation

Chair conformation: It is most stable because all H atoms are in staggered form.
 Twist-boat conformation: Where it twists, two H atoms
are at staggered position.
 Boat form: All H-atoms are at eclipsed form.
 Half-Chair form: Because at one end of ring are planar

Effect of electron donating/withdrawing group on carbocation