Convenient access to 1,3,4-trisubstituted pyrazoles carrying 5-nitrothiophene moiety via 1,3-dipolar cycloaddition of sydnones with acetylenic ketones and their antimicrobial evaluation

Article abstract of DOI:10.1016/j.ejmech.2007.08.002

Novel 1-aryl-3-(5-nitro-2-thienyl)-4-aroyl-pyrazoles 7 have been synthesized by the 1,3-dipolar cycloaddition of 3-arylsydnones 3 with 1-aryl-3-(5-nitro-2-thienyl)-2-propyn-1-ones 6. The newly synthesized compounds were well characterized by elemental analysis, IR, ¹H NMR and mass spectral studies. They were also screened for their antibacterial and antifungal activities against a variety of microorganisms and the results of such studies have been discussed in this article.

Full text of DOI:10.1016/j.ejmech.2007.08.002

Available online at www.sciencedirect.com
European Journal of Medicinal Chemistry 43 (2008) 1715e1720
http://www.elsevier.com/locate/ejmech
Original article
Convenient access to 1,3,4-trisubstituted pyrazoles carrying
5-nitrothiophene moiety via 1,3-dipolar cycloaddition of sydnones
with acetylenic ketones and their antimicrobial evaluation
a
b
N. Satheesha Rai a, Balakrishna Kalluraya a, , B. Lingappa , Shaliny Shenoy ,
*
Vedavati G. Puranic c
a Department of Post-Graduate Studies and Research in Chemistry, Mangalore University, Mangalagangothri-574 199, Karnataka, India
b Department of Micorbiology, KMC Mangalore, India
c Centre for Materials Characterization, National Chemical Laboratory, Pune, India
Received 30 March 2007; received in revised form 18 August 2007; accepted 20 August 2007
Available online 30 August 2007
Abstract
Novel 1-aryl-3-(5-nitro-2-thienyl)-4-aroyl-pyrazoles 7 have been synthesized by the 1,3-dipolar cycloaddition of 3-arylsydnones 3 with 1-
1
aryl-3-(5-nitro-2-thienyl)-2-propyn-1-ones 6. The newly synthesized compounds were well characterized by elemental analysis, IR, H NMR
and mass spectral studies. They were also screened for their antibacterial and antifungal activities against a variety of microorganisms and
the results of such studies have been discussed in this article.
Ó 2007 Elsevier Masson SAS. All rights reserved.
Keywords: Sydnone; Pyrazole; Acetylenic ketone; 1,3-Dipolar cycloaddition; 5-Nitrothiophene; Antibacterial; Antifungal
1. Introduction
studied extensively pretty long back [3e6]. However, less at-
tention has been paid on the regiochemistry of 1,3-dipolar cy-
cloaddition of sydnones with more complex dipolarophiles. In
literature the reaction of sydnones with symmetrical dipolaro-
philes like dimethyl acetylenedicarboxylate (DMAD) and
methyl propiolate has been reported. But less attention was
given for the reaction between sydnones and unsymmetrical
acetylenic ketones (dipolarophiles).
The incorporation of 5-nitrofuran or 5-nitrothiophene moi-
ety into various heterocyclic systems has found to increase
their biological activities. We have reported a few heterocyclic
systems carrying 5-nitrofuran moiety as potent antimicrobial
agents [7]. In continuation of our studies on 1,3-dipolar cyclo-
addition reactions of sydnones with dipolarophiles carrying ni-
trofuran or nitrothiophene moiety [8], we herein report the
synthesis of some new pyrazoles possessing 5-nitrothiophene
nucleus and evaluated them for their biological properties.
The results of such studies are discussed in this article.
Chemotherapeutic activity of nitro heterocycles is almost
always associated with compounds having the nitro group at-
tached to C-5 of the five memebered heterocycles containing
appropriate substituents at C-2 [1].
The pyrazole nucleus constitute an interesting class of or-
ganic compound with diverse chemical applications [2].
They possess antipyretic, antitumour, tranquilizing and herbi-
cidal activities. Sydnones are easily accessible aromatic com-
pounds and versatile synthetic intermediates with a masked
azomethine imine unit. The 1,3-dipolar cycloaddition reaction
with various dipolarophiles offers a convenient synthetic route
for the preparation of pyrazole derivatives and has been
* Corresponding author. Tel.: þ91824 2287262; fax: þ91824 2287367.
E-mail address: bkalluraya_2001@yahoo.com (B. Kalluraya).
0223-5234/$ - see front matter Ó 2007 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2007.08.002

1716
N. Satheesha Rai et al. / European Journal of Medicinal Chemistry 43 (2008) 1715e1720
2. Chemistry
R2
COCH3
+
(AcO)2HC
NO2
S
In continuation of our earlier work we studied the 1,3-
dipolar cycloaddition [9] reaction of 3-arylsydnone with
acetylenic ketones carrying 5-nitrothiophene [10] moiety.
Substituted anilines when treated with ethyl chloroacetate in
the presence of sodium acetate in ethanol medium gave the
corresponding anilino acetic ester. This ester on hydrolsis
gave the corresponding aniline acetic acid 1. Diazotization
of the anilino aceticacid 1 with sodium nitrite and conc.
HCl at 0 ꢀC gave the corresponding nitroso compound 2.
Cyclisation of this nitroso compound with acetic anhydride
gave 3-arylsydnone 3 (Scheme 1). The various acetylenic
ketones 6 were obtained by the dehydrobromination of
corresponding dibromides 5. Dibromides 5 were obtained by
the bromination of propenones 4. Propenones 4 were inturn
obtained by the condensation of appropriate aryl ketone with
5-nitro thiophenediacetate in ethanol medium employing
conc. sulphuric acid as the catalyst (Scheme 2).
EtOH, Conc H2SO4
O
4
S
R2
NO2
Br2 /AcOH
Br
O
S
Br
R2
5
NO2
The title compounds 1-aryl-3-(5-nitro-2-thienyl)-4-aroyl-
pyrazoles 7 were obtained by the treatment of acetylenic
ketones 6 with 3-arylsydnones 3 in dry xylene under reflux
(Scheme 3). The structures of the newly synthesized
compounds have been established on the basis of elemental
Et3N/dry C6H6
O
1
analysis, IR, H NMR and mass spectral studies.
S
NO2
6
3. Biological activity
6a -R2 = H
R2
The newly synthesized pyrazoles 7 were screened for their
antibacterial and antifungal activities. The antibacterial
6b -R2 = Me
6c -R2 = Cl
6d -R2 = OMe
COOEt
COOH
Scheme 2.
NH2
HN
HN
COOEt
EtOH,AcONa
Heat
i) OH-/H2O
H+
+
Cl
activity was studied against four bacterial strains, namely Es-
cherichia coli (ATCC-25922), Staphylococcus aureus (ATCC-
25923), Pseudomonas aeruginosa (ATCC-27853), Bacillus
subtilis (recultured) and antifungal activity was studied against
a fungi namely Candida albicans (NCIM No. 3100) by serial
dilution method [11,12].
R1
R1
R1
1
NaNO2/HCl 0°C
The test compound was dissolved in dimethylformamide
(5 mL) to prepare a stock solution of concentration 1000
(mg/mL). One loop full of an 18-h broth culture was inoculated
into 5 mL of nutrient broth and this was incubated at 37 ꢀC for
4 h. An assay was prepared by diluting with labeled test tubes
1e11. An aliquot 0.5 mL of stock solution of test compound
was added to the first tube. The solution was mixed well
and 0.5 mL of this solution was transferred into second tube.
This process was repeated serially to obtain the quantities in-
dicated in each of the test tubes. The eleventh tube was taken
as growth control. Drops of diluted broth culture of the test or-
ganism (approximately 0.5 mL) were added into all the tubes
using a sterilized Pasteur pipette. The solutions were mixed
gently and the incubation was carried out at 37 ꢀC for 16e
18 h. Nitrofurazone dissolved in dimethylformamide was
used as standard drug for antibacterial study and fluconazole
O
COOH
O
ON
N
N
H
N
AC2O
Heat
R1
R1
2
3
3a -R1 = H
3b -R1 = Me
3c -R1 = OMe
Scheme 1.

N. Satheesha Rai et al. / European Journal of Medicinal Chemistry 43 (2008) 1715e1720
1717
4. Results and discussion
O
O
The antibacterial and antifungal screenings revealed that
some of the tested compounds showed good inhibition at
0.125 mg/mL concentration. The antibacterial screening indi-
cated that among the tested compounds 7d, 7e and 7f showed
excellent activity against all the tested bacterial strains namely
S. aureus, E. coli, P. aeruginosa and B. subtilis. The remaining
compounds were found to be moderately active.
N
O
H
N
+
S
NO2
R2
R1
The antifungal screening revealed that among the tested
compounds 7d, 7e, 7f and 7g showed excellent activity against
the tested fungal strain namely C. albicans. The remaining
compounds were also equipotent as that of the standard
drug. The higher potency of compounds 7d, 7e and 7f may
be due to the presence of chlorine in the aryl moiety. So these
pyrazoles may be suitable as possible antimicrobial agents.
1,3-Dipolar cycloaddition reaction of sydnones with acetyle-
nic ketones containing 5-nitrothiophene moiety in it has re-
sulted in the formation of biologically active pyarazoles.
6
3
dry-xylene, Δ
NO2
O
S
R2
7a -R1 = H,
7b -R1 = H,
R2 = Me
N
N
R2 = OMe
7c -R1 = Me, R2 = H
7d -R1 = Me, R2 = Me
5. Conclusions
7e -R1 = H,
R2 = Cl
A series of pyrazoles namely 1-aryl-3-(5-nitro-2-thienyl)-4-
aroyl pyrazoles have been synthesized and screened for their
antibacterial and antifungal activities. The antibacterial and anti-
fungalscreeningresultssuggest thatamongthecompoundstested
7d, 7e and 7f have exhibited higher activity against all the tested
microorganisms compared to the standard. Pyrazole nucleus is
one of the active components present in many standard drugs.
The presence of 5-nitrothiophene moiety is also instrumental in
contributing to the net biological activity of the system.
R1
7f -R1 = Me, R2 = Cl
7g -R1 = OMe, R2 = Cl
7
7h -R1 = H,
R2 = H
7i -R1 = OMe, R2 = H
7j -R1 = OMe, R2 = Me
Scheme 3.
6. Experimental protocols
was employed as the standard for antifungal studies. The
concentration at which there was no turbidity was taken as
minimum inhibitory concentration (MIC) and the results are
tabulated in Table 1.
6.1. General
Melting points were determined using open capillary
method and are uncorrected. All compounds were analyzed
Table 1
Antibacterial and antifungal activity data of compounds 7aej
Compound
Antibacterial activity (MIC in mg/mL)
Antifungal activity (MIC in mg/mL)
S. aureus
E. coli
P. aeruginosa
B. subtilis
C. albicans
7a
7b
0.25
0.25
0.25
0.125
0.125
0.125
0.25
0.25
0.25
0.25
0.25
e
0.25
0.25
0.25
0.125
0.125
0.125
0.25
0.25
0.25
0.25
0.25
e
0.25
0.25
0.25
0.125
0.125
0.125
0.25
0.25
0.25
0.25
0.25
e
0.25
0.25
0.25
0.125
0.125
0.125
0.25
0.25
0.25
0.25
0.25
e
0.25
0.25
0.25
0.125
0.125
0.125
0.125
0.25
0.25
0.25
e
7c
7d
7e
7f
7g
7h
7i
7j
Standard: nitrofurazone
Standard: fluconazole
Control: DMF
0.25
e
e
e
e
e

1718
N. Satheesha Rai et al. / European Journal of Medicinal Chemistry 43 (2008) 1715e1720
satisfactorily for C, H, and N. The IR spectra (in KBr pellets)
were recorded on a JASCO FT IR 430 spectrophotometer. The
1H NMR spectra were recorded on a Bruker AMX-400
(400 MHz) NMR spectrometer using TMS as an internal stan-
dard. The chemical shifts are expressed in d scale downfield
from TMS and proton signals are indicated as s ¼ singlet,
d ¼ doublet, t ¼ triplet, q ¼ quartet m ¼ multiplet. The mass
spectra were recorded either on a Jeol JMS-D 300 mass spec-
trometer or API 3000 LCMS instrument operating at 70 eV.
room temperature for overnight. Then it was poured into
ice-cold water, filtered and washed with water, 5% sodium
bicarbonate solution and again with water. The solid was
dried and recrystallised from benzene. Compounds prepared
according to this procedure are 3-phenylsydnone 3a: m.p.
134e35 ꢀC, yield 73% (lit. [7] 134e35 ꢀC), 3-( p-tolyl)syd-
none 3b: m.p. 143e44 ꢀC, yield 78%. (lit. [7] 144e45 ꢀC),
3-( p-anisyl)sydnone 3c: m.p. 125e26 ꢀC, yield 75%. (lit.
[7] 125e26 ꢀC).
6.2. General procedure for the synthesis of N-substituted
glycines (anilino acetic acid) 1aec
6.5. General procedure for the preparation of
1-aryl-3-(5-nitro-2-thienyl)-2-propen-1-ones 4aed
A mixture of substituted aniline (0.5 mol), ethyl chloroace-
tate (73.0 g 0.6 mol) and anhydrous sodium acetate (50 g,
0.6 mol) in 120 mL of ethanol was refluxed in an oil bath
(120e125 ꢀC) for 6 h. The reaction mixture was left overnight
at room temperature and poured into crushed ice. The precip-
itate formed was collected by filtration and dried. The dried
product, ethyl ester of N-substituted glycine without further
purification was used for the next step.
To ethyl ester of N-substituted glycine (0.4 mol), sodium
hydroxide (18 g, 0.45 mol) in 200 mL of water was added
and refluxed for 0.5 h. After cooling, the reaction mixture
was acidified to pH ¼ 2 using hydrochloric acid. The precipi-
tated N-substituted glycine 1 was filtered and washed thor-
oughly with cold water. Further purification was done by
recrystallisation from ethanol. The compounds prepared by
this procedure are anilino acetic acid 1a: m.p. 127e28 ꢀC,
yield 70% (lit. [7] 128e29 ꢀC), p-methylanilino acetic acid
1b: m.p. 163e64 ꢀC, yield 75% (lit. [7] 163e64 ꢀC), p-
methoxyanilino acetic acid 1c: m.p. 142 ꢀC, yield 75% (lit.
[7] 144e45 ꢀC).
A
solution of 5-nitro-2-thiophenealdehyde diacetate
(2.5 g, 0.01 mol) and an appropriate acetophenone
(0.01 mol) in ethanol (20 mL) was treated with conc. sulfuric
acid (2 mL). The mixture was stirred for 4 h and allowed to
stand at room temperature for 24 h. The precipitated crystals
of propenones were collected by filtration, washed with eth-
anol, dried and recrystallised from ethanol. Characterization
data of the compounds prepared as per this procedure is
given in Table 2.
6.6. General procedure for the preparation of
2,3-dibromo-1-aryl-3-(5-nitro-2-thienyl)propan-
1-ones 5aed
1-Aryl-3-(5-nitro-2-thienyl)-2-propen-1-one 4 (0.01 mol)
was dissolved in glacial acetic acid (25 mL) by gentle warm-
ing. A solution of bromine in glacial acetic acid (30% w/v)
was added to it with constant stirring till the yellow color of
bromine persisted. The reaction mixture was kept aside at
room temperature overnight. Crystals of dibromopropanones
separated out. They were collected by filtration and washed
with ethanol. It was dried and recrystallised from glacial acetic
acid. Characterization data of the compounds prepared as per
this procedure is given in Table 3.
6.3. Preparation of N-nitroso-N-substituted
glycines 2aec
To a stirred suspension of N-substituted glycine 1
(0.1 mol) in water at 120 mL at 0 ꢀC, a solution of sodium
nitrite (6.9 g, 0.1 mol) in water 24 mL was added drop
wise during 30 min. The reaction mixture was practically
clear after 2 h. It was filtered and acidified with concentrated
hydrochloric acid. The precipitated product was filtered,
washed with cold water and dried in air. The nitrosoglycines
2 prepared by the above method were recrystallised from
aqueous ethanol. Compounds prepared according to this pro-
cedure are N-nitroso-N-phenylglycine 2a: m.p. 101e02 ꢀC,
yield 80% (lit. [7] 102e03 ꢀC), N-nitroso-N-( p-tolyl)glycine
2b: m.p. 98e99 ꢀC, yield 83% (lit. [7] 99e100 ꢀC), N-
nitroso-N-( p-anisyl)glycine 2c: m.p. 120e21 ꢀC, yield 84%
(lit. [7] 121 ꢀC).
6.7. General procedure for the preparation of 1-aryl-3-
(5-nitro-2-thienyl)-2-propyn-1-ones 6aed
To a stirred solution of 2,3-dibromo-1-aryl-3-(5-nitro-2-
thienyl)propan-1-one (0.01 mol) 5 in dry benzene (100 mL),
a solution of triethylamine (4 g, 0.04 mol) in dry benzene
(30 mL) was added. The reaction mixture was stirred at
room temperature for 24 h. The resulting mass of
Table 2
Characterization data of 1-aryl-3-(5-nitro-2-thienyl)-2-propen-1-ones: 4aed
Compound
R2
M.p. (ꢀC)
Crystal nature
6.4. Preparation of 3-arylsydnone 3aec
4a
4b
4c
4d
H
176e77 (177)
169e70 (170)
224e25 (225)
207 (207)
Yellowish flakes
Brown crystals
Yellow needles
Yellow needles
Me
Cl
N-Nitroso-N-substituted glycine 2aec (0.1 mol) was
heated with acetic anhydride (56 mL, 0.5 mol) on a water
bath for 2e4 h. The reaction mixture was kept aside at
OMe
The values within the parenthesis indicate the literature [8] melting point.

N. Satheesha Rai et al. / European Journal of Medicinal Chemistry 43 (2008) 1715e1720
1719
Table 3
Characterization data of 2,3-dibromo-1-aryl-3-(5-nitro-2-thienyl) propan-1-
ones: 5aed
Table 4
Characterization data of 1-aryl-3-(5-nitro-2-thienyl)-2-propyn-1-ones: 6aed
Compound
R2
M.p. (ꢀC)
Crystal nature
Compound
R2
M.p. (ꢀC)
Crystal nature
6a
6b
6c
6d
H
154e56 (155)
152e53 (153)
181e82 (182)
165e67 (167)
Brown crystals
Brown crystals
Brown crystals
Yellowish needles
5a
5b
5c
5d
H
144e45 (145)
150e52 (151)
170e71 (170)
158e59 (159)
Brown crystals
Brown needles
Me
Cl
Me
Cl
Pale yellow crystals
Shining yellow crystals
OMe
OMe
The values within the parenthesis indicate the literature [8] melting point.
The values within the parenthesis indicate the literature [8] melting point.
protons of p-tolyl, J ¼ 10.1 Hz), 7.52e7.88 (m, 5H, AreH),
8.23 (s, 1H, pyrazole-5H); LCMS, m/z; 390 (Mþ þ 1).
triethylamine hydrobromide was removed by filtration and the
filtrate was concentrated by distilling the benzene under re-
duced pressure. The concentrated solution was cooled to
room temperature. The product that formed was collected by
filtration and washed with ethanol. It was dried and recrystal-
lised from ethanol. Characterization data of the compounds
prepared as per this procedure are given in Table 4.
6.8.1.4. Compound 7d: 1-p-tolyl-3-(5-nitro-2-thienyl)-4-( p-
methylbenzoyl) pyrazole. IR (KBr,g cmꢁ1); 1646 (C]O),
1577 (C]N), 1524 (NO2e asymmetric), 1339 (NO2e sym-
1
metric); H NMR (CDCl3) d: 2.42 (s, 3H, CH3), 2.46 (s, 3H,
CH3), 7.41 (d, 1H, thiophene-3-H), 8.05 (d, 1H, thiophene
4-H), 7.26 (d, 2H, o-protons of p-tolyl, J ¼ 9.8 Hz), 7.80 (d,
2H, m-protons of p-tolyl, J ¼ 9.8 Hz), 7.61 (d, 2H-o-protons
of p-tolyl, J ¼ 10.2 Hz), 7.87 (d, 2H, m-protons of p-tolyl,
J ¼ 10.2 Hz), 8.19 (s, 1H, pyrazole-5H);LCMS, m/z; 403
(Mþ þ 1).
6.8. General procedure for the synthesis of
1-aryl-3-(5-nitro-2-thienyl)-4-aroyl pyrazoles 7aej
3-Arylsydnone
3 (0.01 mol) and 1-aryl-3-(5-nitro-2-
thienyl)-2-propyn-1-one 6 (0.01 mol) were dissolved in
10 mL dry xylene and refluxed for 3e4 h. After completion
of the reaction (monitored by TLC and evolution of CO2)
the solvent was removed by distillation under reduced pres-
sure. The crude product obtained was purified by recrystallisa-
tion from ethanol and DMF mixture. The yield, melting point
and other characterization data of these compounds are given
in Table 5.
6.8.1.5. Compound 7f: 1-p-tolyl-3-(5-nitro-2-thienyl)-4-( p-
chlorobenzoyl) pyrazole. IR (KBr,g cmꢁ1); 1634 (C]O),
1523 (C]N), 1413 (NO2e asymmetric), 1333 (NO2e sym-
metric); 1H NMR (CDCl3) d: 2.44 (s, 3H, CH3), 7.35 (d,
1H, thiophene-3-H), 7.97 (d, 1H, thiophene 4-H), 7.54 (d,
2H, o-protons of p-tolyl, J ¼ 10.5 Hz), 7.85 (d, 2H, m-protons
of p-tolyl, J ¼ 10.5 Hz), 7.66 (d, 2H-o-protons of p-chloro-
phenyl, J ¼ 11.7 Hz), 7.89 (d, 2H-m-protons of p-chloro-
phenyl, J ¼ 11.7 Hz), 8.18 (s, 1H, pyrazole-5H); LCMS, m/z;
424 (Mþ þ 1).
6.8.1. Data for compounds 7aej
6.8.1.6. Compound 7g: 1-p-anisyl-3-(5-nitro-2-thienyl)-4-( p-
cholorbenzoyl) pyrazole. 1H NMR (CDCl3) d: 3.89 (s, 3H,
OCH3), 7.05 (d, 1H, thiophene-3-H), 7.97 (d, 1H, thiophene-
4-H), 7.51 (d, 2H, o-protons of p-anisyl, J ¼ 11.6 Hz), 7.67
(d, 2H, m-protons of p-anisyl, J ¼ 11.6 Hz), 7.53 (d, 2H-o-pro-
tons of p-chlorophenyl, J ¼ 11.9 Hz), 7.83 (d, 2H-m-protons of
p-chlorophenyl, J ¼ 11.9 Hz), 8.13 (s, 1H, pyrazole-5H);
LCMS, m/z; 440 (Mþ þ 1).
6.8.1.1. Compound 7a: 1-phenyl-3-(5-nitro-2-thienyl)-4-( p-
methylbenzoyl) pyrazole. 1H NMR (CDCl3) d: 2.423 (s, 3H,
CH3), 7.32 (d, 1H, thiophene-3-H), 7.89 (d, 1H, thiophene
4-H), 7.45 (d, 2H, o-protons of p-tolyl, J ¼ 10.5 Hz), 7.98
(d, 2H, m-protons of p-tolyl, J ¼ 10.5 Hz), 7.52e7.63 (m,
5H, AreH), 8.19 (s, 1H, pyrazole-5H); LCMS, m/z; 390
(Mþ þ 1).
6.8.1.7. Compound 7h: 1-phenyl-3-(5-nitro-2-thienyl)-4-
6.8.1.2. Compound 7b: 1-phenyl-3-(5-nitro-2-thienyl)-4-p-(me-
thoxybenzoyl) pyrazole. 1H NMR (CDCl3) d: 3.77 (s, 3H,
OCH3), 7.02 (d, 1H, thiophene-3-H), 7.66 (d, 1H, thiophene
4-H), 7.52 (d, 2H, o-protons of p-anisyl, J ¼ 11.6 Hz), 7.88
(d, 2H, m-protons of p-anisyl, J ¼ 11.6 Hz), 7.53e7.63 (m,
5H, AreH), 8.13 (s, 1H, pyrazole-5H); LCMS, m/z; 405
(Mþ þ 1).
1
benzoyl pyrazole. H NMR (CDCl3) d: 7.06 (d, 1H, thiophene-
3-H), 7.56 (d, 1H, thiophene-4-H), 7.58e7.64 (m, 10H, AreH),
8.11 (s, 1H, pyrazole-5H); LCMS, m/z; 376(Mþ þ 1).
6.8.1.8. Compound 7j: 1-phenyl-3-(5-nitro-2-thienyl)-4-( p-
methylbenzoyl) pyrazole. 1H NMR (CDCl3) d: 1.56 (s, 3H,
CH3), 3.89 (s, 3H, OCH3), 7.66 (d, 1H, thiophene-3-H), 7.99
(d, 1H, thiophene-4-H), 7.02 (d, 2H, o-protons of p-tolyl,
J ¼ 11.5 Hz), 7.56 (d, 2H, m-protons of p-tolyl,
J ¼ 11.5 Hz), 7.68 (d, 2H-o-protons of p-anisyl,
J ¼ 11.6 Hz), 7.89 (d, 2H-m-protons of p-anisyl,
6.8.1.3. Compound 7c: 1-p-tolyl-3-(5-nitro-2-thienyl)-4-ben-
zoyl pyrazole. 1H NMR (CDCl3) d: 2.46 (s, 3H, CH3), 7.33
(d, 1H, thiophene-3-H), 7.92 (d, 1H, thiophene 4-H), 7.44
(d, 2H, o-protons of p-tolyl, J ¼ 10.1 Hz), 8.05 (d, 2H, m-

1720
N. Satheesha Rai et al. / European Journal of Medicinal Chemistry 43 (2008) 1715e1720
Table 5
Characterization data of 1-aryl-3-(5-nitro-2-thienyl)-4-aroyl pyrazoles 7aej
Compound
R1
R2
Molecular formula
M.p. (ꢀC)
Yield (%)
Crystal nature
Percentage analysis
found (calculated)
C
H
N
7a
7b
7c
7d
7e
7f
H
Me
OMe
H
C
21H15N3O3S
C21H15N3O4S
21H15N3O3S
145e47
200e02
182e84
135e37
205e07
195e97
150e52
125e27
127e29
108e09
71
73
75
73
72
77
78
80
75
76
Bright yellow
Bright yellow
Light yellow
Light yellow
Bright yellow
Bright yellow
Bright yellow
Light yellow
Bright yellow
Bright yellow
64.79 (64.78)
62.10 (62.2)
64.65 (64.78)
65.49 (65.5)
58.59 (58.61)
59.49 (59.51)
57.37 (57.34)
63.9 (64)
3.86 (3.85)
3.69 (3.7)
10.76 (10.79)
10.29 (10.3)
10.78 (10.79)
10.41 (10.42)
10.23 (10.25)
9.89 (9.91)
H
Me
Me
H
C
3.86 (3.85)
4.20 (4.21)
2.91 (2.93)
3.29 (3.30)
3.23 (3.18)
4.85 (4.87)
3.69 (3.7)
Me
Cl
C22H17N3O3S
C20H12N3O3SCl
C21H14N3O3SCl
Me
OMe
H
Cl
Cl
7g
7h
7i
C21H14N3O4SCl
9.38 (9.55)
H
C20H13N3O3S
C22H15N3O4S
C22H17N3O4S
11.19 (11.2)
10.31 (10.3)
10.01 (10.02)
OMe
OMe
H
Me
62.19 (62.2)
63.1 (63)
7j
4.09 (4.05)
Solvent for recrystallisation: ethanol:DMFT 4:2.
[4] R. Huisgen, R. Grashey, H. Gotthardt, R. Schmidt, Angew. Chem., Int.
Ed. 1 (1962) 49.
J ¼ 11.6 Hz), 8.15 (s, 1H, pyrazole-5H); LCMS, m/z; 420
(Mþ þ 1).
[5] D.L. Hammick, D.J. Voeden, J. Chem. Soc. (1965) 5875e5880.
[6] P.M. Weintraub, J. Chem. Soc. (1970) 760.
[7] J.C. Hegde, G. Rai, V.G. Puranic, B. Kalluraya, Synth. Commun. 36
(2006) 1285e1290.
Acknowledgements
The authors thank Head, RSIC, Chandigarh, and CDRI,
Lucknow, for spectral and analytical data. The authors are
also thankful to UGC New Delhi for the financial assistance
through Major Research Project.
[8] B. Kalluraya, A. D’Souza, B.S. Holla, Indian J. Chem. 33B (1994)
1017e1022.
[9] N.S. Rai, B. Kalluraya, Indian J. Chem. 46B (2007) 375e378.
[10] B. Kalluraya, A. D’Souza, B.S. Holla, Indian J. Chem. 34B (1995)
939e943.
[11] Z.K. Khan, In vitro and vivo screening techniques for bioactivity screen-
ing and evaluation, in: Proceeding of International Workshop, UNIDO-
CDRI, 1997, p. 210.
References and notes
[12] R.S. Verma (Ed.), Antifungal Agents: Past, Present and Future
Prospectus, National Academy of Chemistry and Biology, India,
Lucknow, 1998.
[1] B. Kalluraya, Sreenivasa, Il. Farmaco 53 (1998) 399e404.
[2] R.B. Pathak, S.C. Bahel, J. Indian Chem. Soc. 57 (1989) 1108e1112.
[3] R. Huisgen, H. Gotthardt, R. Grashey, Angew. Chem., Int. Ed. 1 (1962) 48.