Pyrazoles having two groups of nitrogens one of them is basic and another one is neutral. It have anti cancer , anti microbial properties.

1. Annu
M.Sc. (Chemistry)
4th sem.
Roll no:-180000701002
CH. BANSILAL UNIVERSITY BHIWANI
2019-20
Heterocyclic compound pyrazole
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2. CONTENTS Introduction
 Pyrazole synthesis.
a) Knorr pyrazole synthesis.
b) Tandem reaction.
c) From hydrazine and various Michael acceptors.
d) Aromatic aldehydes and tosylhydrazine.
e) From vinyl ketones.
 Reactions of pyrazole.
1. Catalytic reduction.
2. Oxidation.
 Medicinal use.
 Conclusion.
 References.
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3. Introduction
 Pyrazoles are important members of heterocyclic compounds with two
adjacent nitrogens in a five membered ring system.
 Among the two nitrogen atoms; one is basic and the other is neutral in
nature.
 These are aromatic molecules due to their planar conjugated ring
structure with six delocalized pi electrons.
 The unshared pair of electrons present on the –NH nitrogen.
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4. Pyrazole synthesis
a) Knorr pyrazole synthesis.
 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 acid catalyst.
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5. Mechanism
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6. b).Tandem reactions
 In this reaction enones were synthesized from acid chlorides and
terminal alkynes and were converted in situ into pyrazoles by the
cycloaddition of hydrazines. The method has easy isolation and simple
workup procedures.
 Tandem reaction refers to two reactions operating in succession in the
same reaction vessel.
 It is an efficient and one pot three component procedure.
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7. Mechanism
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8. c).From hydrazine and various Michael
acceptors.
Visible light photoredox catalysis enables a selective and high
yielding synthesis of polysubstituted pyrazoles in very good
yields from hydrazine and various Michael acceptors under very
mild reaction conditions in the presence of air as the terminal
oxidant.
The reaction proposed to go through VLPC- promoted oxidation
of hydrazine to diazene followed by its addition to Michael
acceptors.
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9. Mechanism
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10. d).Aromatic aldehyde and
tosylhydrazines
 An efficient , one pot , three component procedure for the
preparation of 3,5-disubstituted 1 H-pyrazoles includes
condensation of substituted aromatic aldehydes and
tosylhydrazine followed by cycloaddition with terminal alkynes.
 The reaction tolerates various functional groups.
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11. Mechanism
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12. e).From vinyl ketones.
 The cyclocondensation reaction between an alpha,beta-
ethylenic ketone and a hydrazine derivative results in the
synthesis of pyrazolines which after oxidation provide the
pyrazole ring.
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13. Mechanism
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14. Reaction of pyrazole
1.Catalytic reduction
 When pyrazole is reduced in the presence of H2-Pd reagent to
form pyrazoline or dihydrapyrazole.
 Again pyrazoline react with reducing agent to form
pyrazolidine.
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15. 2.Oxidation
 Pyrazole ring are stable to the action of oxidising agents, but the
side chain may be oxidised to carboxylic acid.
 When 3-methyl-1-phenyl pyrazole are react with alk. KMnO4 it
forms 1-phenyl pyrazole -3-carboxylic acid.
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16. Medicinal use
 Antibacterial and Antifungal Activity
 Akbas et at. Synthesized of series 1H-pyrazole-3-carboxylic acid
derivatives and evaluated for their antibacterial activities against
Bacillus cereus.
 Staphylococcus aureus, Escherichia coli and pseudomonas
putida.
 The results showed that the compound (1) was the best
compound in the series, exhibiting antibacterial activity against
both Gram-positive and Gram negative.
 A series of new pyrazoles containing a quinolinyl chalcone group
were synthesized and accessed for antibacterial activity.
 Compound (2) was the most potent against bacterial and fungal
strains.
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18. Anticancer Activity
 A new class of pyrazole-oxindole were synthesized and
investigated for their antiproliferative activity on different
human cancer cell lines.
 Pyrazole derivatives synthesized by Viale et al. were secrenned
for their antiproliferative activity.
 A series of substituted pyrazole compounds were synthesized
and evaluated in vitro for their anticancer effects on a panel of 60
cellular lines.
 A series of 3,5-diarylpyrazole derivatives were synthesized and
evaluated for their anticancer activity against five cell lines
(breast cancer, prostate cancer, promyelocytic leukemia, lung
cancer, colon cancer).
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20. Anti-Inflammatory and Analgesic
Activity
 A new group of pyrazole derivatives were designed for
evaluation as selective cyclooxygenase-2 (COX-2)
inhibitors .
 Results indicated the compound (1) exihibited
significant COX-2 inhibition.
 A series of 1H-pyrazolyl derivatives were described by
Bekhit et al. and tested for their in vivo anti-
inflammatory activity.
 Compound (2) exhibited anti-inflammatory activity
and showed good selective inhibitory activity against
COX-2 enzyme.
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22. Anti-Tubercular Activity
 Manetti et al. identify new inhibitors of Mycobacterium
tuberculosis.
 Compound (1) was found to be most active agent.
 A series of 3-substituted 5-hydroxy-5-trifluoro[chloro]methyl-
1H-1-isonicotinoyl-4,5-dihydropyrazoles were synthesized by
Almeida da Silva et al. and tested for their in vitro antimicrobial
activity against Mycobacterium tuberculosis H37Rv, INH-
resistant clinical M.tuberculosis isolates non tuberculous
mycobacteria.
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24. Conclusions
Pyrazoles represent a major pharmacophore with
various biological properties and some pyrazole
containing derivatives have already been used for
therapeutic purposes.
It has been noted so far that the structural
modifications of the basic structure of pyrazol, have
allowed the preparation of new derivatives with a
broad spectrum of biological activity.
It has an antimicrobial, anticonvulsant, analgesic, anti-
inflammatory, anti-viral, anti-malarial and anti-cancer
properties.
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25. References
 Fustero,S.; Sanchez-Rosello, M.; Barrio, P.; Simon-Fuentes,
A. From 2000: A fruitful decade for the synthesis of
pyrazoles. Chem. Rev. 2011, 111, 6984-7034, doi:
10,1021/cr2000459.
 Ansari, A,; Ali, A.; Asif, M. Biologically active pyrazole
derivatives. New J.Chem.2017, 41, 16-41, doi:
10.1039/C6NJ03181A.
Hampp, C.; Hartzema, A.G.; Kauf, T.L. Cost-utility analysis
of rimonabant in the treatment of obesity. Value Health
2008, 11, 389-399, doi: 10.11 11/j.1524-4733.2007.00281.x.
Luttinger, D.; Hlasta, D.J. Antidepressant Agents. Annu.
Rep. Med. Chem. 1987, 22, 21-30, doi:10.1016/S0277-
5387(96)00346.4.
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