This document discusses heterocyclic compounds, specifically pyrazoles. It describes pyrazoles as a 5-membered heterocyclic ring containing two nitrogen atoms at the 1st and 2nd positions. Several common synthesis routes for pyrazoles are outlined, including the Paal-Knorr synthesis using 1,3-dicarbonyl compounds and hydrazines. The document also reviews reactions that pyrazoles undergo, such as electrophilic substitution, oxidation, and reduction. Finally, some medicinal uses of pyrazoles are provided, including their use as anti-pyretic, analgesic, and anti-inflammatory drugs.

1. Unit 4
HETEROCYCLIC
COMPOUNDS II
Lecture by
Sowmiya Perinbaraj,
M.Pharm
Assistant Professor
Dept of Pharmaceutical
Chemistry
SVCP

2. 1. PYRAZOLE
❖ Pyrazole is an unsaturated five membered
heterocyclic ring consists of two nitrogens as
heteroatoms at 1st and 2nd positions.
❖ Molecular Formula: C3H4N2

3. SYNTHESIS
1. Paal-knorr synthesis:
✓ 1,3-dicarbonyl compound react with hydrazine or its derivative to give
pyrazole derivatives.
✓ A simple pyrazole is obtained with a 1,3-dicarbonyl compound such as
acetylacetone and hydrazine or phenyl hydrazine.

4. SYNTHESIS
2. From α,β- ethylene carbonyl compounds:
➢ it is an important synthesis consists of a reaction between an
α,β- ethylene carbonyl derivative and hydrazine.

5. SYNTHESIS
3. Addition of diazo compound to acetylenic
compound:
➢ A Diazo compound adds to an acetylenic derivative which
has its triple bond activated by an electron withdrawing
substituent.
➢ The reaction is usually carried out in a suitable solvent at
room temperature.
➢ Methyl diazoacetate and methyl phenyl propionate yield
isomeric pyrazoles in equal amounts.

7. SYNTHESIS
4. From other ring systems:
➢ Various heterocyclic compounds transform to pyrazoles under
appropriate conditions.
➢ Syndone and acrylonitrile result in pyrazole formation.

8. REACTIONS
1. Electrophilic Substitution reaction:
❖ Pyrazole undergoes electrophilic substitution at 4th position.
❖ Electrophile attacks at possible positions with intermediates.

9. REACTIONS
i) Nitration:
ii) Sulphonation:
NH
N
NH
N
HO3S
Pyrazole-4-sulphonic acid
H2SO4

10. ii) Halogenation:
iv) Friedel crafts reaction has limited application
in pyrazole chemistry.

11. REACTIONS
2. Oxidation:
Pyrazole ring is stable to the action of oxidising agents, but the side chain
may oxidised to carboxylic acid.
3. Reduction:

12. 4. N-Alkylation and N-Acylation:

13. REACTIONS
5. Ring opening Reaction:

14. Medicinal uses
1. Antipyrine- used as anti-
pyretic drug
2. Analgin- analgesic
and anti-pyretic drug

15. Medicinal uses
3. Phenylbutazone- used as
anti-pyretic, analgesic and
anti-inflammatory drug
(NSAID)
4. Oxyphenbutazone- used
as anti-pyretic, analgesic
and anti-inflammatory drug
(NSAID)

16. Medicinal uses
5. Phenazone- used as
anti-pyretic, analgesic
6. Celecoxib- anti-
inflammatory drug (NSAID)