Introduction:
Pyrazole and their derivatives have long been used as precursors for the synthesis of biologically
active molecules. Because of the wide spectrum of activity shown by the pyrazole moiety,
numerous pyrazole substituted with different groups at various positions have been prepared. In
recent years several new methods for the preparation of pyrazole derivatives and reactions have
been reported. The heterocyclization of these derivatives inspired us to undertake the aspect on
pyrazole derivatives.
Pyrazole exhibits characteristic reactions of pyrrole and pyridine because of containing pyrrole
type and pyridine type nitrogen atoms at the position-1 and position-2. Pyridine type nitrogen is
susceptible to electrophilic attack but it is less nucleophilic than the pyridine nitrogen atom. The
hydrogen atom attached to the nitrogen atom in pyrazole is more acidic then the pyrrolic N-H in
pyrrole and can be easily removed by nucleophiles. Pyrazole exists in two tautomeric forms.
N
NH
N
N
H
Heterocyclic compounds are predominant among the types of compounds used as
pharmaceutical, agrochemical and veterinary products. One of the most useful classes in this
category is pyrazole. The pyrazole ring consists of a doubly unsaturated five membered ring
containing two adjacent nitrogen atoms. In 1883, Knorr [1,2] first synthesized a compound by
the reaction of ethyl acetoacetate with phenyl hydrazine, which yields 1-phenyl-3-methyl-5-
pyrazoline. The name pyrazole was given to such compounds because the nucleus was derived
from pyrrole by replacement of carbon by nitrogen. Much research has been carried out with the
aim to find the therapeutic values of pyrazole moiety, since their discovery [3-5]. Various
pyrazole and its derivatives have been used in many drugs [6-8].
CH3
N
O
N
C6H5
(II)
Different methods of preparation of pyrazoles are available in literature. Palmey synthesized two
structurally isomeric pyrazoles by the reaction of the substituted hydrazines with 1,3-dicarbonyl
compounds., Esribano et al synthesized some pyrazoles by the reaction of ethyl aceto-acetate
with aryl hydrazine hydrate. Jacobs reported the synthesis by the reaction of acetylene with
diazomethane. Whereas, Singh and Ojha synthesized pyrazoles by the reaction of ethyl
acetoacetate with aryl hydrazines. Some workers reported synthesis by reaction of acetonitrile
derivatives with (DMF-DMA)[9]. Others synthesized by the cyclo-condensation of mono-
substituted hydrazines with enaminones afforded pyrazoles [10].
Pyrazole derivatives have been reported to be associated with diverse biological activities. Drug
molecules having pyrazole nucleus with good pharmacological activities are listed below.
C N
MeO
N
N
N
CH3
N N
O
N
CH 3
N OH
O
Cl
CH 3
Tepoxalin
Zaleplon
(Sedative, Hypnotic) (Antiinflammatory)
N O
CF 3
N CH2 SO 3 Na
N
N
CH 3
H 2NO 2S H3 C
CH 3
Novalgin
Celecixib
(Antiinflammatory) (Antipyretic, Analgesic)
CF3
H 3 C ( H 2 C )3 O
N
O N
Cl Cl
N NH N OH
N
N
S C H2F CN
P y r a flu p r o le O x y p h e n b u ta z o n e
(A n tia r th r itic )
(In s e c tis id e )
CH 3
CH 3 OH
CH 3 O O CH 3
N P CH 3 H
N O CH 3
O
N H H
N
Cl N
H H
Chlorprazophos Stanozolol
(Insectiside)
(Insectiside)