The document discusses the electrophilic substitution reactions in pyridine, emphasizing that such reactions predominantly occur at the 3-position due to the stability of the intermediate carbonium ion formed at that position. It highlights that pyridine is less reactive towards electrophilic substitution compared to benzene due to the electronegativity of nitrogen, which decreases the electron density in the ring. The document also explains why reactions at the 2 and 4 positions are less favorable, outlining the mechanisms and conditions for nitration and sulfonation of pyridine.

1. 1
B.Sc. Final year
MEB Students
for
Today’s
Chemistry Lecture
by
Dr Pramod R Padole

2. 2

4. LOGO
A) Heterocyclic Compounds:

5. LOGO
b) 6-membered Heterocyclic compounds
(ii) Pyridine or AZABENZENE:
Molecular Formula of Pyridine is C5H5N
..
N
Pyridine

6. LOGO
Orientation of Electrophilic
Substitution in Pyridine:
In pyridine, electrophilic substitution occur at
3-position (β-position) only rather than 2-or
4-position.

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Orientation and Reactivity of
Electrophilic Substitution in
Pyridine:
Q.1) Discuss / Describe the orientation of electrophilic
substitution in pyridine.
(S-10, S-12, W-13, W-17, S-18 & W-19, 4-5 Mark)
Q.2) Explain why pyridine is less reactive to elctrophilic
substitution than benzene?
Q.3) At which position pyridine undergoes electrophilic
substitution.
Q.4) On the basis of stability of intermediate carbonium ion
show that in pyridine, electrophilic substitution take place
at 3-position than 2- or 4-position.
Q.5) Explain why, pyridine undergoes C3 electrophilic
substitution reaction rather than C2 attack. (S-16, 4 Mark)

8. General Mechanism of Aromatic
Electrophilic Substitution:

H
+ E
slow
RDS
H E H E H E
I II III
H E
Benzene
Resonance structures of carbonium ion
Resonance hybrid
(-complex)


electrophile

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Reactivity of Electrophilic
Substitution in Pyridine:
Pyridine can undergo electrophilic
substitution, when extremely vigorous
reaction conditions are used.
Considerably less reactivity of pyridine
than benzene towards electrophilic
substitution is because of the following
reasons-
(1) The nitrogen atom in pyridine, because
of its electronegativity lowers the
electron density around the ring carbons;
and

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Reactivity of Electrophilic
Substitution in Pyridine:
 According to resonance theory, pyridine is the resonance
hybrid of the following resonating structure –
 Thus, the overall pyridine ring is electron deficient and
positively charged carbons as shown in resonance hybrid.
 Since, nitrogen (more EN) accepts the electrons, so
positively charged on the ring increases and deactivates
the pyridine ring towards electrophilic substitution
reaction.
 Hence, pyridine is less reactive to electrophilic
substitution reaction than benzene.
N N N N
Pyridine I II III
.. .. .. .. N

 
..
Resonance hybridResonating structures of Pyridine
1 1 1 1
1
2 2
3 3
4
44
3
2
5 5
6 6
6
6
5
4
4
3
2
2

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Reactivity of Electrophilic
Substitution in Pyridine:
(2) Electrophiles (E+) can coordinate
with the lone pair of electrons on
nitrogen; to form stable pyridinium
cation.
N
E
N
Pyridinium cation (Stable)
EPyridne
Electrophile

12. ..
N
Pyridine
N
..
Pyridine
N
..
Pyridine
1
2 / 6
3 / 5
4 / 4
6 / 2
5 / 3

13. N
..
Pyridine
1
2 / 6
3 / 5
4 / 4
6 / 2
5 / 3
Attack of E+ at ?

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Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):1
Attack of E+ at 3-position (at C-3):2
Attack of E+ at 4-position (at C-4):3
In pyridine, electrophilic substitution occur at
N
..
Pyridine
1
2 / 6
3 / 5
4 / 4
6 / 2
5 / 3

15. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 3-position (at C-3):1
N N
E
E
H
N
E
H
N
E
H
- H
3- Substituted Pyridine
M O R E S T A B L E
H
Favoured product
Three resonating structures
C-3
I II III
.. .. .. ..
attack
at
1
2
3
4
5
6
3 3
3
6
2
4
N
E3
..

16. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 3-position (at C-3):1
N
E
H
C-3
..
attack
at
1
2
3
4
5
6
N
E
H
I
..
3
4
Resonating structurePyridine
Electrophile

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By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 3-position (at C-3):1
N
E
H
I
..
3
4
Resonating structure Resonating structure
N
E
H
II
..
3
6

18. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 3-position (at C-3):1
Resonating structure
N
E
H
II
..
3
6
Resonating structure
N
E
H
III
..
3
2

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By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 3-position (at C-3):1
- H
Resonating structure
N
E
H
III
..
3
2
3- Substituted Pyridine
Favoured product
N
E3
..

20. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 3-position (at C-3):1
N N
E
E
H
N
E
H
N
E
H
- H
3- Substituted Pyridine
M O R E S T A B L E
H
Favoured product
Three resonating structures
C-3
I II III
.. .. .. ..
attack
at
1
2
3
4
5
6
3 3
3
6
2
4
N
E3
..
As a result, three intermediate carbonium ions
obtained by the attack at C-3 position

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By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):2
attack
at
1
2
3
4
5
6
N N
E E
H N
E
H
N
E
H
- H
L E S S S T A B L E
AH
C-2
Ignored
Favourable Two structures
I II
.. .. .. ..
5
1
3
2-Substituted
pyridine
N 2
.. E

22. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):2
attack
at
1 2
3
4
5
6
N
E
H
C-2
..
N
E
H
L E S S S T A B L E
A
Ignored
.. 1
Resonating structure ‘A’ which is obtained by the electrophilic attack
at C-2, is energetically unfavorable and hence it is ignored
because the nitrogen atom in these structure has
only six electrons.
X

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By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):2
N
E
H
L E S S S T A B L E
A
Ignored
.. 1
N
E
H
I
..
5
Resonating structure
2

24. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):2
N
E
H
I
..
5
Resonating structure
2
Resonating structure
N
E
H
II
..
3

25. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):2
Resonating structure
N
E
H
II
..
3
- H
2-Substituted
pyridine
N 2
.. E

26. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):2
attack
at
1
2
3
4
5
6
N N
E E
H N
E
H
N
E
H
- H
L E S S S T A B L E
AH
C-2
Ignored
Favourable Two structures
I II
.. .. .. ..
5
1
3
2-Substituted
pyridine
N 2
.. E
Thus, attack at C-2 position gives only two
resonating structures.
X

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By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 4-position (at C-4):3
attack
at
1
2
3
4
5
6
C- 4
N
4
..
N
N
E
NN
E H
E H
E H
- H
B
L E S S S T A B L E 4- Substituted
pyridine
H
I II
Favourable Two structures (Structure I & II)
Ignored
.. .. ..
..
4 4
4
3
1
5
E

28. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 4-position (at C-4):3
attack
at
1
2
3
4
5
6
C- 4
N
E
H
..
Pyridine
N
E H
I
..
4
3
Resonating structure

29. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 4-position (at C-4):3
N
E H
I
..
4
3
Resonating structure
N
E H
B
L E S S S T A B L E
Ignored
..
4
1
Resonating structure ‘B’ which is obtained by the electrophilic attack
at C-4, is energetically unfavorable and hence it is ignored
because the nitrogen atom in these structure has
only six electrons.
X

30. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 4-position (at C-4):3
Resonating structure
N
E H
B
L E S S S T A B L E
Ignored
..
4
1
Resonating structure
N
E H
II
..
4
5

31. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 4-position (at C-4):3
N
E H
- H
II
..
4
5
Resonating structure
N
4
..
4- Substituted
pyridine
E

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attack
at
1
2
3
4
5
6
C- 4
N
4
..
N
N
E
NN
E H
E H
E H
- H
B
L E S S S T A B L E 4- Substituted
pyridine
H
I II
Favourable Two structures (Structure I & II)
Ignored
.. .. ..
..
4 4
4
3
1
5
E
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 4-position (at C-4):3
Thus, attack at C-4 position gives only two
resonating structures.
X

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By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 3-position (at C-3):1
N N
E
E
H
N
E
H
N
E
H
- H
3- Substituted Pyridine
M O R E S T A B L E
H
Favoured product
Three resonating structures
C-3
I II III
.. .. .. ..
attack
at
1
2
3
4
5
6
3 3
3
6
2
4
N
E3
..
As a result, three intermediate carbonium ions
obtained by the attack at C-3 position

34. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 2-position (at C-2):2
attack
at
1
2
3
4
5
6
N N
E E
H N
E
H
N
E
H
- H
L E S S S T A B L E
AH
C-2
Ignored
Favourable Two structures
I II
.. .. .. ..
5
1
3
2-Substituted
pyridine
N 2
.. E
Thus, attack at C-2 position gives only two
resonating structures.
X

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attack
at
1
2
3
4
5
6
C- 4
N
4
..
N
N
E
NN
E H
E H
E H
- H
B
L E S S S T A B L E 4- Substituted
pyridine
H
I II
Favourable Two structures (Structure I & II)
Ignored
.. .. ..
..
4 4
4
3
1
5
E
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
Attack of E+ at 4-position (at C-4):3
Thus, attack at C-4 position gives only two
resonating structures.
X

36. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
N N
E
E
H
N
E
H
N
E
H
- H
3- Substituted Pyridine
M O R E S T A B L E
H
Favoured product
Three resonating structures
C-3
I II III
.. .. .. ..
attack
at
1
2
3
4
5
6
3 3
3
6
2
4
N
E3
..
attack
at
1
2
3
4
5
6
N N
E E
H N
E
H
N
E
H
- H
L E S S S T A B L E
AH
C-2
Ignored
Favourable Two structures
I II
.. .. .. ..
5
1
3
2-Substituted
pyridine
N 2
.. E
attack
at
1
2
3
4
5
6
C- 4
N
4
..
N
N
E
NN
E H
E H
E H
- H
B
L E S S S T A B L E 4- Substituted
pyridine
H
I II
Favourable Two structures (Structure I & II)
Ignored
.. .. ..
..
4 4
4
3
1
5
E
X
X

37. www.themegallery.com
By Dr Pramod R Padole
Orientation of Electrophilic Substitution in Pyridine:
N N
E
E
H
N
E
H
N
E
H
- H
3- Substituted Pyridine
M O R E S T A B L E
H
Favoured product
Three resonating structures
C-3
I II III
.. .. .. ..
attack
at
1
2
3
4
5
6
3 3
3
6
2
4
N
E3
..
As a result, three intermediate carbonium ions obtained
by the attack at C-3 position are more stable (due to more
resonating structures, i.e., three structures).
Hence, in pyridine, 3-eletrophilic substituted product is
more favourable (stable) product than C-2 & C-4
product.
If C-3 position is already blocked, eletrophilic substitution
will occur at other available at C-5 position.

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39. Electrophilic Substitution Reactions of Pyridine
at C-3 position:
Reaction with
Con.HNO3
or Con.KNO3
in presence
of Con.H2SO4:
Chemical Reactions
(ii) Sulphonation:
(i) Nitration:
Reaction with
fuming
Sulphuric acid (H2SO4):

40. (i) Nitration:
Reaction with Con.HNO3
or Con.KNO3
in presence of Con.H2SO4:

41. companyname
(i) Nitration:
Con.HNO3
in presence
of
Con.H2SO4
Reaction
with
Con.KNO3
in presence
of
Con.H2SO4
Q.1) How does pyridine reacts with nitrating mixture? (W-15, 2 Mark)
Q.2) How will you convert pyridine to 3-nitro-pyridine? (S-19, 2 Mark)

42. companyname
(i) Nitration:
Reaction with Con.HNO3 or Con.KNO3
in presence of Con.H2SO4:
 When pyridine is heated with concentrated nitric acid
(con. HNO3) or potassium nitrate (con.KNO3) in the
presence of concentrated sulphuric acid (con.H2SO4)
at 300oC (573K), undergoes nitration; to form
3-nitro-pyridine in poor (less) yield.
3
N
Conc. H2SO4
0
N
NO2
573KHO-NO2
HNO3
or
+ KO-NO2
or KNO3
300 C or
(- H2O)
Conc. H2SO4
0
573K300 C or
(- KOH)
Pyridine 3-nitro-pyridine
H
3 + H2O
+ KOH

43. Fuming sulfuric acid is a mixture of pyrosulphuric
acid, H 2 S 2 O 7, and other condensed acids, made by
dissolving sulphur trioxide in concentrated sulphuric acid.
Also called: oleum, Nordhausen acid
Q.1) What is the difference between
sulfuric acid and fuming sulfuric acid?
 The key difference between oleum
and sulfuric acid is that the oleum is sulfur
trioxide in sulfuric acid whereas the sulfuric
acid is an inorganic acid having the chemical
formula H2SO4. We call oleum as “fuming
sulfuric acid” as well. ...
 Sulfuric acid, on the other hand, is a syrupy
liquid, which is highly water soluble.

44. pramodpadole@gmail.com By Dr Pramod R Padole
(ii) Sulphonation:
Reaction with fuming Sulphuric acid (H2SO4):
 When pyridine is heated with fuming sulphuric acid (H2SO4) in the
presence of mercuric sulphate (HgSO4) as a catalyst at 230oC (503K);
to form pyridine-3- sulphonic acid.
Q.1) Complete the following reaction. (W-18, 2 Mark)
Q.2) How will you convert pyridine to Pyridine 3-sulphonic acid
(S-19, 2 Mark)
?
N
Fuming H2SO4
33
N Fuming H2SO4
N
SO3H
HgSO4HO - SO3H
or at 230 o
C
Pyridine Pyridine-3-sulphonic acid
H
+ H2O

45. LOGO

46. LOGO
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