Unit 4 Pyrazole

Pharmaceutical Organic Chemistry 3 B.Pharm IV sem

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

2. 1. PYRAZOLE
❖Pyrazoleisanunsaturatedfivemembered
heterocyclicringconsistsoftwonitrogensas
heteroatomsat1
st
and2
nd
positions.
❖MolecularFormula:C
3H
4N
2

3. SYNTHESIS
1.Paal-knorrsynthesis:
✓1,3-dicarbonylcompoundreactwithhydrazineoritsderivativetogive
pyrazolederivatives.
✓Asimplepyrazoleisobtainedwitha1,3-dicarbonylcompoundsuchas
acetylacetoneandhydrazineorphenylhydrazine.

4. SYNTHESIS
2.Fromα,β-ethylenecarbonylcompounds:
➢itisanimportantsynthesisconsistsofareactionbetweenan
α,β-ethylenecarbonylderivativeandhydrazine.

5. SYNTHESIS
3. Addition of diazo compound to acetylenic
compound:
➢ADiazocompoundaddstoanacetylenicderivativewhich
hasitstriplebondactivatedbyanelectronwithdrawing
substituent.
➢Thereactionisusuallycarriedoutinasuitablesolventat
roomtemperature.
➢Methyldiazoacetateandmethylphenylpropionateyield
isomericpyrazolesinequalamounts.

7. SYNTHESIS
4.Fromotherringsystems:
➢Variousheterocycliccompoundstransformtopyrazolesunder
appropriateconditions.
➢Syndoneandacrylonitrileresultinpyrazoleformation.

8. REACTIONS
1.Electrophilic Substitution reaction:
❖Pyrazoleundergoeselectrophilicsubstitutionat4
th
position.
❖Electrophileattacksatpossiblepositionswithintermediates.

9. REACTIONS
i) Nitration:
ii) Sulphonation: NH
N
NH
N
HO
3
S
Pyrazole-4-sulphonic acid
H
2
SO
4

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

11. REACTIONS
2. Oxidation:
Pyrazole ring is stableto 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)