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Archana et al., Chem Sci J 2020, 11:1
Chemical Sciences Journal
ISSN: 2150-3494
Research Article
Open Access
An Efficient One Pot Synthesis and Biological Screening of Some Pyrazole
Based Heterocycles
Archana D. Jadhav1*, Pankaj U. Barhate1 and Ayesha N. Durrani2
1Department
of Chemistry, Arts, Science and Commerce College, Rahuri, Ahmednagar, Maharashtra, India
2Department
of Chemistry, Dr. Rafiq Zakaria College of Womens, Naukhanda, Aurangabad, Maharashtra, India
*Corresponding
author: Archana DJ, Department of Chemistry, Arts, Science and Commerce College, Rahuri, Ahmednagar, Maharashtra, India, Tel: +919545171462;
E-mail: archu1990jadhav@gmail.com
Received date: February 06, 2020; Accepted date: March 03, 2020; Published date: March 10, 2020
Copyright: © 2020 Archana DJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Present work deals with the preparation of some Pyrazole derivative salts which was prepared by using different
kinds of aldehydes and hydrazine derivatives by using alkoxide as a base and using the 1,3- dicarbonyl compound
like ethyl acetoacetate at room temperature. The reaction mixture was stirred on magnetic stirrer for about 10 to 20
minutes till colour change is observed and then product is separated by using organic solvent. The product obtained
was converted to sodium salt of Pyrazole derivative by base hydrolysis. The entire synthesized compound was
tested for their antibacterial activity against the Gram-positive and Gram-negative strains of bacteria. The
investigation of antibacterial screening data revealed that most of the tested compounds showed moderate to good
antibacterial activity.
Keywords: Antibacterial; Hydrazine hydrate/Phenyl hydrazine
hydrochloride; Alkoxide
Introduction
Pyrazole is amongst the most important privileged scaffolds found
in synthetic and natural products of medicinal interest.Pyrazole
containing molecules possess a wide range of biological activities such
asantibacterial, antifungal, antiviral, anticancer, antidiabetic, antiinflammatory, etc.Considering the valuable potential of pyrazoles,
numerous synthetic methods were developed over the past
decades.There are two classical methods for the synthesis of pyrazoles
first is 1,3-dipolar cycloaddition reaction of diazo-compounds with
alkynes and second one condensation reaction of 1,3-dicarbonyls with
hydrazine’s. Although these methods provide pyrazoles in acceptable
yields, they suffer from their own limitations such as the use of
hazardous transition metals and limited substrate scope, poor
regioselectivity and time consuming.Therefore Pyrazole synthesis was
investigated extensively and several improved synthetic routes were
developed [1-5]. In recent years one pot three component synthesis has
been taken a greater importance as it synthesize the most important
pyrazole and its different kinds of derivative in just a single step. In our
experiment we have tried to decrease the reaction time required to
complete the reaction for that purpose we had successfully driven our
reaction, by Biginilli type of condensation in basic medium and those
synthesized compounds were subjected to antibacterial activity to
compare their potentials.
recorded on Bruker AV, 200 MHz spectrometers in appropriate
solvents using TMS as internal standard or the solvent signals as
secondary standards and the chemical shifts was shown in δ scale.
Multiplicities of 1H NMR signals are designated as s (singlet), d
(doublet), dd (doublet of doublet), dt (doublet of triplet), t (triplet),
quin (quintet), m (multiplet) etc. IR data were recorded an Alpha-T
ATR-FTIR.
General procedure for preparation of pyrazole derivative
In present work we prepared pyrazole salt by using different kinds
of aldehyde and hydrazine derivatives by using alkoxide as a base. In
this one pot condensation 0.01mol of an aldehyde, (0.01) mol of
hydrazine derivative and (0.01) mol of 1,3-dicarbonyl compound was
taken in RB flask and reaction mix was stirred on magnetic stirrer for
10-15 min till color change is observed [11-15].
Materials and Methods
All the chemicals and solvents were obtained from E-Merck, and SD
fine chemicals L.T.D. India (AR, LR grade) Melting points were
determined in open capillaries in liquid paraffin bath and are
uncorrected [6-10]. Purity of the compound was routinely checked on
silica gel TLC plates using CHCl3 as solvent. 1H NMR spectra were
Chem Sci J, an open access journal
ISSN: 2150-3494
Figure 1: Scheme of the synthesis.
Volume 11 • Issue 1 • 1000205
Citation:
Archana DJ, Pankaj UB, Ayesha ND (2020) An Efficient One Pot Synthesis and Biological Screening of Some Pyrazole Based
Heterocycles. Chem Sci J 11: 205.
Page 2 of 5
S. No.
R1
R2/ R3
Ar
Time (min.)
M.P. (°C)
Yield (%)
A*1
4-NO2
H
4 - NO2 Ph
1
154
75
2
3,4-OMe
H
3,4-O MePh
7
174
72
3
3-NO2
H
3- NO2 Ph
1
140
78
4
H
H
Ph
10
120
68
B*1
4-NO2
Ph
4 - NO2 Ph
15
170
63
2
3,4-OMe
Ph
3,4-O MePh
15
186
72
3
3-NO2
Ph
3- NO2 Ph
15
152
66
4
H
Ph
Ph
15
132
58
Table 1: Experimental data.
Then work up of the reaction is carried out and product separated
by using organic solvent. Product was dried, yield, M.P. and spectral
analysis was carried out. The Scheme of the synthesis was shown in
Figure 1. Results were shown in Table 1 and respective image was
shown in Figure 2.
Figure 2: Graphical representation of results.
Antibacterial activity
The plates were inoculated by specific microorganism by spread
plate technique; bores were made in the solidified agar plate by using a
sterile borer [16-20]. The test solution of specified concentration was
Chem Sci J, an open access journal
ISSN: 2150-3494
added in the bore by using sterile pipette and the plates were kept in
freeze for 1hour for diffusion and then incubated at 37°C for 24 hours.
After 24 hours the plates were examined and zone of inhibition were
recorded. All the synthesized compounds were screened for
antibacterial activity against both gram positive S. aureus and Bascillus
Volume 11 • Issue 1 • 1000205
Citation:
Archana DJ, Pankaj UB, Ayesha ND (2020) An Efficient One Pot Synthesis and Biological Screening of Some Pyrazole Based
Heterocycles. Chem Sci J 11: 205.
Page 3 of 5
substilis and gram negative E. coli and Proteus vulgaris bacteria at a
concentration of 100 µg/ml, 200 µg/ml, 400 µg/ml, 800 µg/ml [21-25].
Azithromycin is used as standard for comparison of anti-bacterial
activity. In presence of base such as NaOH and ethanol was used as a
solvent. The results of screening are given in Tables 2 and 3 and
respective graphical representation was shown in Figures 3 and 4.
Zone of inhibition (mm)
Compound
Staphylococcus aureus
Bacillus subtilis
100 µg
200 µg
400 µg
800 µg
100 µg
200 µg
400 µg
800 µg
A* 1
10
12
13
17
12
14
15
17
2
10
12
12
15
12
15
15
17
3
7
8
11
15
8
10
12
15
4
10
12
13
15
09
11
13
16
B* 1
11
13
14
15
11
12
14
15
2
12
14
16
18
12
14
18
20
3
7
9
14
18
7
10
13
15
4
12
13
16
17
10
12
14
17
Azithromycin
13
14
17
19
15
17
18
21
Table 2: Zone of inhibition for gram positive bacteria graphical representation.
Figure 3: Graphical representation of results.
Zone of inhibition (mm)
Compound
Escherichia coli
Proteus vulgaris
100 µg
200 µg
400 µg
800 µg
100 µg
200 µg
400 µg
800 µg
A* 1
9
11
12
14
9
11
12
14
2
10
11
13
14
10
11
14
15
3
10
12
14
16
10
12
14
16
4
8
10
12
14
7
8
10
12
B* 1
9
11
12
15
8
10
12
12
Chem Sci J, an open access journal
ISSN: 2150-3494
Volume 11 • Issue 1 • 1000205
Citation:
Archana DJ, Pankaj UB, Ayesha ND (2020) An Efficient One Pot Synthesis and Biological Screening of Some Pyrazole Based
Heterocycles. Chem Sci J 11: 205.
Page 4 of 5
2
9
11
13
15
11
12
13
14
3
11
12
14
15
9
11
14
15
4
8
10
11
13
8
8
11
12
Azithromycin
14
15
16
18
12
14
16
17
Table 3: Zone of inhibition for gram negative bacteria graphical representation.
Figure 4: Graphical representation of results.
Amongst all synthesized compounds sodium 3- (3,4dimethoxyphenyl)
-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate
were found to be more potent as antibacterial Staphylococcus aureus
and Bacillus subtilis agents. Whereas compound sodium 5-methyl-3(3-nitrophenyl) -1H-pyrazole-4-carboxylate was more active against
antibacterial Escherichia coli and Proteus vulgaris as antibacterial
[26-30]. The zone of inhibition of synthesized compounds was
compared with the standard drug Azithromycin at four different
concentrations [31-36].
Spectral data
Spectral analysis of given Pyrazole can carried out by NMR spectra
& IR spectroscopy:
IR (KBr) 3300-3500 cm-1 (Ar-N-H), 1680-1600 cm-1 (C=C), 1550
cm-1 (C=N), 1300cm-1 (C-N), 1400 cm-1 (-COO– Na +), 900-690 cm-1
(Ar-CH3 out of plane)
1H-NMR (DMSO) 8.61 δ (s, 1H, Ar-NH), 7.84 δ (s, 2H,Ar-H), 7.48
δ (s, 2H,Ar-H), 7.46 δ (s, 1H,Ar-H)
• Yield 78% mp, 140°C.
IR (KBr) 3300-3500 cm-1 (Ar-N-H), 1500 cm-1 (C=N),1600 cm-1
(C=C), 1400 cm-1 (-COO– Na +), 1390-1300 cm-1 (m- NO2), 900-690
cm-1 (Ar-CH3 out of plane)
1H-NMR (DMSO) 8.29 δ (s, 1H, Ar-NH), 7.73 δ (td, 1H,Ar-H), 8.19
δ (d, 1H,Ar-H), 8.17δ (dd, 1H,Ar-H), 7.59 δ (dd, 1H,Ar-H)
Conclusion
• Yield 72% mp, 174°C.
cm-1
cm-1
IR (KBr) 3300-3500
(Ar-N-H), 1680-1600
(C=C), 1550
cm-1 (C=N), 1350-1000 cm-1, (C-N), 1400 cm-1 (-COO – Na +),
900-690 cm-1 (Ar-CH3 out of plane) .
1H-NMR (DMSO) 8.61 δ (s, 1H, Ar-NH), 3.98 δ (s, 3H, p-OCH3),
3.94 δ (s, 3H, m-OCH3), 6.91 δ (d, 1H,Ar-H), 7.25 δ (dd,1H,Ar-H),
7.24 δ (d, 1H,Ar-H) .
The main target of our reaction is to reduce the reaction time and
efficiency of the product. Here, we have presented an operationally
simple, suitable, fast, efficient method for the preparation of Pyrazole
derivative. The main focus of this research work was to synthesize,
purify, characterize and evaluate antibacterial activities of the
synthesized compounds &which shows good antibacterial activity.
• Yield 63% mp, 170°C.
Acknowledgements
IR (KBr) 1390-1300 cm-1 (p- NO2), 1500 cm-1 (C=N), 1600 cm-1
(C=C), 1400 cm-1 (-COO– Na +), 3000 cm-1 (=C-H) i.e., (sp2) (C-H),
900-690 cm-1 (Ar-CH3 out of plane).
1H-NMR (DMSO) 7.3 δ (m, 5H,Ar-H), 8.2 δ (d, 2equ.H 3J = 7Hz,
Ar-H), 7.7 δ (d, 2 equ.H 3J = 7 Hz, Ar-H)
• Yield 68% mp, 120°C.
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ISSN: 2150-3494
The authors wishto express a deep sense of gratitude to the
respectedPrincipal of Dr. Maqdoom Farooqui of Dr. Rafiq Zakaria
College for Womens, Aurangabad for providing the necessary lab
facilities and constant encouragement and perceptive criticism while
completing the research work. We thank Prin. Dr. S. A. Pathare of
Loknete Ramdas Patil Dhumal Arts, Science and Commerce College,
Rahuri and all teaching and non-teaching staff Department of
Volume 11 • Issue 1 • 1000205
Citation:
Archana DJ, Pankaj UB, Ayesha ND (2020) An Efficient One Pot Synthesis and Biological Screening of Some Pyrazole Based
Heterocycles. Chem Sci J 11: 205.
Page 5 of 5
Chemistry, for their kind co-operation. We also thankful to Prof.
Honde Bharat of Shri Vivekanand Nursing Home Trust's College of B.
Pharmacy, Shrishivajinagar.
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