The document discusses the Knorr pyrazole synthesis reaction which converts hydrazines or derivatives and 1,3-dicarbonyl compounds to pyrazoles using an acid catalyst. The mechanism involves acid-catalyzed imine formation on either carbonyl carbon, followed by attack of the other nitrogen on the other carbonyl group. This forms a diimine compound which deprotonates to generate the final pyrazole product. Several examples of pyrazoles synthesized using this reaction are mentioned, including antipyrine, celecoxib, and metamizole sodium which have various medical applications.

1. Knorr Pyrazole Synthesis
Presented by:
Mohd Shafeeque
M. Pharm. 1st Sem.
(Pharm. Chemistry)
Jamia Hamdard

2. The Knorr pyrazole synthesis is an
organic reaction used to convert a
hydrazine or its derivatives and a 1,3-
dicarbonyl compound to a pyrazole
using an acidcatalyst

3. MECHANISM

4. Themechanism begins withan acidcatalyzedimine
formation, wherein thecaseof hydrazinederivatives
theattackcanhappen on eithercarbonylcarbon
and resultin two possible products.The other
nitrogenof thehydrazinederivativethenattacksthe
other carbonylgroup whichhas also been
protonatedbytheacidand forms a second imine
group.This diiminecompound gets deprotonated
to regeneratetheacidcatalystand providethefinal
pyrazoleproduct.

8. APPLICATION:
Used forthesynthesisofmetalchelate,
photographic dyes,herbicidesand biologically
activecompounds.

9. ANTIPYRINE
N
N
C
H3
C
H3
O
1,5-Dimethyl-2-phenylpyrazole-3-one

10. Mechanism of Action:
Antipyrine is thought to act primarily in the
CNS, increasing the pain threshold by
inhibiting both isoforms of cyclooxygenase,
COX-1, COX-2, and COX-3 enzymes
involved in prostaglandin (PG) synthesis.

11. Synthesis of Antipyrine:
EAA Phenylhydrazine
C
H3
OC2H5
O
O
+
NH2
N
H
Ph
Heat
Condensation
N
N
O
C
H3
Ph
+ C2H5OH
N
N
O
C
H3
Ph
H
CH3I
N
N
O
C
H3
Ph
CH3

12. CELECOXIB
4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzene-1-sulfonamide

13. Mechanism of Action:
Inhibition of prostaglandin synthesis,
primarily via inhibition of cyclooxygenase-2
(COX-2), and at therapeutic concentration
in humans, Celecoxib does not inhibit the
cyclooxygenase-1 (COX-1) isoenzyme.

14. Synthesis of Celecoxib:

15. METAMIZOLE SODIUM
[(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-methylamino]methanesulfonic acid

16. Mechanism of Action:
Metamizole is a pro-drug, which spontaneously
breaks down after oral administration to
structurally related pyrazolone compounds.
Apart from its analgesic effect, the medication is
an antipyretic and spasmolytic agent. The
mechanism responsible for the analgesic effect
is a complex one, and most probably rests on
the inhibition of a central cyclooxygenase-3 and
activation of the opioidergic system and
cannabinoid system.

17. Synthesis of Metamizole Sodium:

18. THANK YOU