Introduction

The pyrazole ring is a prominent
structural motif found in numerous pharmaceutically active compounds. This is
mainly due to its ease of preparation and pharmacological activity. Many pyrazole
derivatives are known to possess a wide range of bioactivities such as anti-inflammatory [1], analgesic [2],
antibacterial [3], antifungal [4], and anticancer [5].

 

            The
wide range of biological activities associated with pyrazoles has made them
popular synthetic targets. Numerous methods have been developed for preparation
of substituted pyrazoles.

           

            In
general, pyrazoles are synthesized by

 

(i)                
the reaction of 1,3-diketones with
hydrazines,

(ii)              
1,3-dipolar cycloaddition of diazo
compounds with alkynes

(iii)            
the reaction of ?,?-unsaturated
aldehydes and ketones with hydrazines.

 

Synthesis
of pyrazoles from 1,3-diketones and hydrazines

 

            First synthetic
method for the synthesis of pyrazoles which involves the reactions of
1,3-dicarbonyl compounds with arylhydrazines to afford pyrazoles
derivatives [6].

 

 

 

 

Synthesis of
pyrazoles via 1,3-dipolar cycloaddition of diazoles with alkynes

 

            Alkynes react with diazo compounds
to afford 3,5-disubstituted pyrazoles [7].

 

 

 

 

Pyrazoles
from the reaction of hydrazines with ?,?-unsaturated aldehydes

and
ketones

           

            Another strategy for the synthesis
of pyrazoles is the cyclocondensation of an appropriate hydrazine with a
carbonyl compound having two electrophilic carbons at the 1 and 3 locations [8].

 

 

Literature
review

 

            M. Fedele et al., have synthesized a series of 1- acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles
and were investigated for their ability to inhibit selectively monoamine
oxidases, swine kidney diamine oxidase (SKDAO) and bovine serum amine oxidase (BSAO)
[9].

 

 

           

            B.
P. Anand et al., have synthesised
2-(5-Substituted-1H-pyrazol-3-yl) naphthalen-1-ol derivatives and they
were evaluated for in-vivo anti-inflammatory activity by acute
carrageenan induced paw edema standard method in rats using Indomethacin as a
standard drug [10].

 

 

 

            A. Mathew et al., determined the anticancer
activity of the pyrazole analogues of piperine by MTT
(3-(4,5-Dimethylthiazol-2-yl)-2,5-di phenyl tetrazolium bromide) assay method
[11].

 

 

 

            T. V. Rao et al., have synthesized 1-(5-Methyl-4H-pyrazol-3-yl)methanamine
derivatives and showed significant antibacterial activity [12].

 

           

            Patel VI et al., have synthesized Pyrazole
derivatives and they were screened for anti-tubercular activity [13].

 

 

            G.
M. Nitulescu et al., have synthesized
N-(1-methyl-1H-pyrazole-4-carbonyl)-thiourea derivatives and evaluated
for their analgesic and sedative effects [14].

 

 

 

 

Benzimidazoles

 

            The
benzimidazole ring is an important pharmacophore in modern drug discovery. The
synthesis of novel benzimidazole derivatives remain a main focus of medicinal
research. Recent observations suggested that substituted benzimidazoles show
easy interactions with the biopolymers, possess potential activity with lower
toxicities in the chemotherapeutic approach in man [15]. Several benzimidazole derivatives had been proven to
possess bioactivities such as antiviral [16], antihypertensive [17],
vasodilator [18], anticancer [19] antimicrobial [20], antioxidant and
antiglycation [21].

 

Synthetic
aspects of Benzimidazoles

            Practically all synthetic
processess of benzimidazoles start with benzene derivatives possessing nitrogen
containing functions ortho to each other.

1.     
General synthetic methodology

      Traditionally,
benzimidazole have most commonly been prepared from the reaction of 1,2-diaminobenzenes
with carboxylic acids under harsh dehydrating reaction conditions, utilizing
strong acids such as polyphosphoric acid, hydrochloric acid, boric acid, or p-toluenesulfonic
acid [22].

 

 

2.     
Benzimidazole ring closure

 

            This method is applicable to most
aromatic, unsaturated and aliphatic aldehydes and to substituted
1,2-diaminobenzenes without significant differences. A palladium catalyzed N-arylation
reaction provided a novel synthesis of benzimidazole from (o-bromophenyl)amidine
precursors under microwave irradiation [23].

 

3.      Diels-Alder
reaction

 

            Imidazole o-quinodimethane
intermediate undergoes Diels-Alder reaction with several dienophiles to yield
the benzimidazole derivatives in moderate yields [24].

 

 

Biological
activity

 

            A. Husain et al., synthesized
a series of benzimidazole bearing oxadiazole derivatives and screened for their
in-vitro anticancer activity against full NCI 60 human cell lines on
nine cancer subpanel with significant results [25].

 

 

 

            K.
F. Ansari et al., have synthesized some
benzimidazole derivatives containing oxadiazole like, 1-{[5-(alkyl/aryl)-1,3,4-oxadiazol-2-yl]methyl}-2-alkyl-1H-benzimidazoles
and evaluated their antimicrobial activities [26].

 

 

            R. Sharma et al., have synthesized
certain methyl 5-(?-hydroxy-?-substituted-methyl)-1H-benzimidazole-2-carbomates
and screened them for anthelmintic activity [27].

 

 

            V. K. Pandey et al.,
have synthesized 1,2-disubstituted benzimidazoles and screened them for
antiviral activity [28].

 

            L.
K. Labanauskas et al., have
synthesized 5,6-dialkoxy-2-thiobenzimidazole derivatives which possesses
pronounced antiinflammatory properties [29].

 

            C. Kus et al.,
reported the synthesis and antioxidant properties of novel N-methyl-1,3,4-
thiadiazol-2-amine of benzimidazole class [30].

 

            H. Rajak et al.,
synthesized novel 2,5-disubstituted-1,3,4-thiadiazoles (243) as
potential anticonvulsant activity using standard drug Carbamazepine [31].

 

            P. Pattanayak et al.,
synthesized the new benzimidazole derivatives of
2-amino-5-sulfanyl-1,3,4-thiadiazole and evaluated their antidepressant
activity [32].