Synthesis and antimicrobial activity of coumarin pyrazole pyrimidine 2,4,6(1H,3H,5H)triones and thioxopyrimidine4,6(1H,5H)diones

Article abstract of DOI:10.1007/s00044-012-0078-y

A series of 5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl) methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (4a-f) and dihydro-5-((3-(2-oxo-2H- chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxopyrimidine-4,6(1H,5H) -dione (5a-f) derivatives w

Full text of DOI:10.1007/s00044-012-0078-y

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-012-0078-y
ORIGINAL RESEARCH
Synthesis and antimicrobial activity of coumarin
pyrazole pyrimidine 2,4,6(1H,3H,5H)triones
and thioxopyrimidine4,6(1H,5H)diones
•
S. Vijaya Laxmi B. Suresh Kuarm
•
B. Rajitha
Received: 22 November 2011 / Accepted: 20 April 2012
Ó Springer Science+Business Media, LLC 2012
Abstract A series of 5-((3-(2-oxo-2H-chromen-3-yl)-1-
phenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,
5H)-trione (4a–f) and dihydro-5-((3-(2-oxo-2H-chromen-
3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxopyrimi-
dine-4,6(1H,5H)-dione (5a–f) derivatives were synthesized
by the condensation of 3-(2-oxo2H-chromen-3-yl)-1-
phenyl-1H-pyrazole-4-carbaldehyde (3a–f) with barbituric
acid and thiobarbituric acid in acetic acid under microwave
irradiation method. The newly synthesized compounds
were evaluated for their antibacterial activity against
Bcillus subtilis, Staphylococcus aureus, Staphylococcus
epidermidis, Escherichia coli, Pseudomonas aeoginosa,
and Klebsiella pneumoniae. All the compounds were found
to be moderately active against used microorganisms,
whereas compounds (4d) and (4e) exhibited good anti-
fungal activity against Aspergillus niger.
bacterial strains in the last decades indicates a substantial
need for new classes of antibacterial agents (Chopra et al.,
2008). Pyrazole and Isoxazole derivatives exhibit various
biological properties, viz., bacteriostatic, antidiabetic,
analgesic, antioxident, anti-inflammatory, antimicrobial,
and anticancer (Padmaja et al., 2009; Patricia et al., 2008;
Padmaja et al., 2011; Gadakh et al., 2010; Diana et al.,
2007). It is also known that coumarin derivatives have wide
range of biological and therapeutic properties (Jih et al.,
2011; Gnerre et al., 2000; Khalid et al., 2004; Manolov
et al.,1995; Emmanuel-Giota et al., 2001). Antimicrobial
activity of coumarin derivatives is well documented in the
literature (Smyth et al., 2009; Kawase et al., 2001). Thio-
barbituric acid (TBA) and Barbituric acid (BA) derivatives
are used as antibacterial, (Yan et al., 2009) sedatives,
(David et al., 2007) antidiabetic, (Sandeep et al., 2008)
fungicides (Brouwer et al., 1990; Brouwer et al., 1991), and
antiviral (Esanu et al., 1985; Esanu et al., 1986) agents.
Recently, BA and TBA were reported as anti cancer agents
(Singh et al., 2009). Microwave-assisted organic reaction is
a well-established technique for the synthesis of various
heterocycles. All thermally driven reactions can be accel-
erated by microwave irradiation. Spectacular results, viz.,
shorter reaction time, experimental simplicity, selectivity of
products, easy work up etc., were obtained, giving clear
indication of the potentialities of this technique over con-
ventional heating (Caddick, 1995; Verma, 1999; Mavand-
Keywords Antimicrobial activity ꢀ Barbituric acid ꢀ
Coumarin ꢀ Microwave irradiation ꢀ Pyrazole ꢀ
Thiobarbituric acid
Introduction
Bacterial resistance to antibiotics has increased worldwide
in recent years. In order to combat this new problem, novel
antibiotic compounds/substances need to be found which
are effective (Francesca, 2011). In spite of the large number
of antibiotics and chemotherapeutics available for medical
use, the emergence of old and new antibiotic-resistant
¨
adi and Lidstrom, 2004.). In view of these facts, and as part
of our ongoing studies in developing new anti microbial
agents (Vijaya Laxmi et al., 2011; Suresh et al., 2011), it
was envisaged to construct a system, which combines both
these moieties in a single molecular frame work to explore
the additive effect of antimicrobial activities. In this article,
we wish to report microwave-assisted synthesis of pyrazolyl
coumarin barbiturates and their antimicrobial activity.
S. Vijaya Laxmi ꢀ B. Suresh Kuarm ꢀ B. Rajitha (&)
Department of Chemistry, National Institute of Technology,
Warangal 506004, India
e-mail: rajitabhargavi@yahoo.com
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Med Chem Res
Scheme 1 Synthesis of
compounds 4(a–f) and 5(a–f)
Results and discussion
Table 1 Results of the synthesized compounds 3a–f
Entry Product R1 R2 Yields at (80 °C) Yield at r.t
Synthesis of coumarin pyrazole barbiturate derivatives
4(a–f) and 5(a–f) is outlined in Scheme 1, when 3-acetyl
coumarins 1(a–f) treated with phenyl hydrazine in metha-
nolic acetic acid refluxed for half an hour afforded the
compounds 2(a–f) (Chodankar et al., 1986). Vilsmeier
formylation of these compounds 2(a–f) at room tempera-
ture afforded the compounds 3(a–f) in good yields; how-
ever, in literature the reaction was carried out at 80 °C poor
yields were observed (Chodankar et al., 1986; Selvi and
Perumal, 2002a, b). Hence, we made a comparative study
on vilsmeier formylation, at room temperature (method 1)
and also at 80 °C (method 2) the results are depicted in
Table 1, unexpectedly good yields were observed in
method 1. Structures of the compounds were confirmed by
1H NMR spectral data. Further Knoevenagel condensation
(Thirupathi Reddy et al., 2010) of aldehyde 3(a–f) with BA
and TBA on microwave irradiation, furnished the com-
pounds 4(a–f) and 5(a–f) in good yields (Table 2). We did
a comparative study on conventional and microwave irra-
diation method and observed excellent yields (75–85 %) in
microwave irradiation method within a short period. All
coumarin pyrazole barbiturate analogs provide satisfactory
spectral data. (IR,1H NMR,13CNMR, and Mass spectra). In
IR spectra, bands in the region 3,180–3,200 cm-1 attrib-
uted to NH group of the BA and TBA. Bands at
1,704 cm-1 obtained from the lactone ring of coumarin
C=O, 1,667 and 1,733 cm-1 stretching frequencies were
correspond to the C=O groups of BA. In thiobarbiturates,
C=S stretching frequency was observed at 1,292 cm-1. In
1
2
3
4
5
6
3a
3b
3c
3d
3e
3f
H
H
H
70
72
85
88
87
84
82
86
Cl
Cl
Cl 75
H 73
Br
Br
Br 72
70
7,8 benzo
Table 2 Results of the synthesized compounds 4a–f, 5a–f
Entry Product R1 R2 Conventional Yield Time Yield
method (h)
(%)
(min) (%)
1
4a
4b
4c
4d
4e
4f
H
H
7
8
8
6
7
5
6
7
8
9
35
40
50
40
50
60
50
40
60
40
50
55
5
10
10
10
10
5
85
83
85
80
88
82
82
75
80
86
80
82
2
Cl
H
3
Cl
Cl
H
4
Br
5
Br
Br
6
7,8 benzo
7
5a
5b
5c
5d
5e
5f
H
H
H
Cl
H
5
8
Cl
10
10
10
10
5
9
Cl
10
11
12
Br
Br
Br 10
6
7,8 benzo
1H NMR spectra, the absence of aldehyde proton signal at
d 9.93 and the presence of a signal at the range d 9.7–9.8
(C=C–H) supports the formation of compounds 4(a–f) and
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Med Chem Res
5(a–f). The NH signals of BA were detected at
11.33–11.36 ppm range, while NH signal in TBA was
observed at 11.3–12.47 ppm range. In both the series,
aromatic protons appeared as multiplet in regular aromatic
region at 7.2–8.5 ppm range. 13C-NMR signal at d
158.5–159.3 confirmed lactone carbonyl, signal at d
162.6–162.8 ppm and 163.3–163.6 ppm assign the C=O
groups in BA 4(a–f), where as signal at 178.3 ppm
attributed to C=S group 5(a–f).
spectrophotometer; ciprofloxacin was used as a standard
drug.
Antifungal activity
The ready-made Potato Dextrose Agar (PDA) medium
(Himedia, 39 g) was suspended in distilled water (1,000 mL)
and heated to boiling until it dissolved completely, the med-
ium and petri dishes were autoclaved at pressure of 15 lb/inc2
for 20 min. Agar cup bioassay was employed for testing
antifungal activity. The medium was poured into sterile petri
dishes under aseptic conditions in a laminar flow chamber.
When the medium in the plates solidified, 0.5 mL of (week
old) culture of test organism was inoculated and uniformly
spread over the agar surface with a sterile L-shaped rod.
Solutions were prepared by dissolving the compound in
methanol and different concentrations were obtained (30 and
100 lg/mL). After inoculation, cups were scooped out with
6-mm sterile cork borer and the lids of the dishes were
replaced. To each cup, different concentrations of test solu-
tions (30,100 lg/mL) were added. Controls were maintained
with Methanol and Fluconazole (30 lg/mL). The treated
controls were kept at 27 °C for 48 h. Inhibition zones were
measured and the diameter was calculated in mille meter.
Three to four replicates were maintained for each treatment.
Biological activities
All the compounds 4(a–f) and 5(a–f) were evaluated for
their in vitro antibacterial and antifungal activity (National
Committee for Clinical Laboratory Standards, 1982; Lin-
day, 1962).
Antibacterial activity
Determination of minimum inhibitory concentration
(MIC) of synthetic compounds
The MIC was measured by broth dilution method
(Villanova, 1984). A set of sterile test tubes with nutrient
broth media were capped with cotton plugs (1–9). The
test compound is dissolved in DMSO and a concentration
of 100 lg/mL of the test compound was added to the first
tube, which was serially diluted from 1 to 9. A fixed
volume of 0.5 mL over night culture was added in all the
test tubes and incubated at 37 °C for 24 h. After incu-
bation period, the tubes were measured for turbidity using
Antibacterial activity
All the compounds have shown moderate activity at MIC
on 6 different bacterial strains. Results are summarized in
(Table 3).
Table 3 In vitro antibacterial
MIC (lg/mL)
activity (MIC) values for
compounds 4a–f, 5a–f
Compound
B. subtilis
S. aureus
S. epidermidis
E. coli
P. aeroginosa
K. pneumoniae
4a
300
150
300
150
150
150
300
150
300
600
150
300
24
300
150
300
150
150
300
150
300
150
600
150
150
25
300
150
300
150
150
300
150
600
300
300
300
300
22
300
150
300
600
150
300
600
300
600
300
150
600
20
150
150
150
600
150
150
300
150
300
300
150
150
12.5
150
150
150
150
300
300
150
150
150
150
150
150
25
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
Ciprofloxacin
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Med Chem Res
derivatives of 3-[1-(phenyl-hydrazono)-ethyl]-chromen-2-
one, 0.97 g (0.0035 mol) (2a–f), were added and the reac-
tion mixture was stirred for 8–10 h at room temperature.
Completion of the reaction was monitored by TLC, reaction
mixture was poured into ice-cold water, and neutralized
with 10 % NaOH solution. The crude product precipitated
out was filtered, dried, and recrystallized from ethanol.
Table 4 In vitro antifungal activity (MIC) values for compounds 4d
and 4e
Zone of inhibition (mm)
Compound
A. niger
100 lg
150 lg
4d
14
7
20
10
4e
3-(2-Oxo-2H-chromen-3-yl-)-1-phenyl-1H-pyrazole-4-
Fluconazole
30
carbaldehyde (3a)
1
m.p.: 180–185 °C; H-NMR (DMSO, d, ppm): 7.42–8.47
(m, 10H), 9.25 (s, 1H), 9.93 (s, 1H). MS ESI: m? 1 317
Antifungal activity
(100 %) for the M.F C19H12N2O3, M.Wt 316.
All the synthesized compounds were screened for In vitro
antifungal activity; except compounds 4d and 4e remaining
all the compounds were inactive. In both compounds (4d)
and (4e), analog (4d) was found to be more potent against
Aspergillus niger. Structure–activity relationship studies
revealed that (Table 4) the presence of bromo at 6th
position on coumarin (4d) enhanced the activity, while the
activity is diminished when additional bromo group is
introduced at 8th position on coumarin (4e). Hence, a new
lead compound (4d) with antifungal activity encourages
further optimization to develop more potent and effective
analogs as antimycotic agents.
3-(6-Chloro-2-oxo-2H-chromen-3-1-phenyl-1H-
pyrazole-4-carbaldehyde (3b)
1
m.p.: 190–195 °C; H-NMR (DMSO, d, ppm): 7.46–8.21
(m, 9H), 8.85 (s, 1H), 9.92 (s, 1H).
3-(6,8-Dichloro-2-oxo-2H-chromen-3-yl)-1-phenyl-
1H-pyrazole-4-carbaldehyde (3c)
1
m.p.: 175-180 °C; H-NMR (DMSO, d, ppm): 7.23-8.34
(m, 8H), 8.75 (s, 1H), 9.91 (s, 1H).
3-(6-Bromo-2-oxo-2H-chromen-3-yl)-1-phenyl-1H-
Experimental protocols
pyrazole-4-carbaldehyde (3d)
Chemistry
1
m.p.: 180–185 °C; H-NMR (DMSO, d, ppm): 7.3–8.45
(m, 9H), 8.92 (s, 1H), 9.89 (s, 1H).
The barbitutric acid and thiobarbitutric acid with 98 %
purity were purchased from Merck Company. All melting
points were determined using a Quimis apparatus, Q-340s
13 model and are uncorrected. TLC was performed on
2.0 9 6.0 cm aluminum sheets covered with silica gel
(Sorbent, 200-lm thickness) under ultraviolet radiation.
Ethyl acetate:hexane (2:8) is used as a mobile phase.
Infrared (IR) spectra were obtained using ABB spectro-
13C-NMR (DMSO, d, ppm): 116.4, 118.5, 119.3, 120.6,
121, 123.4, 127.9, 129.7, 131, 132.7, 134.9, 138.5, 141.7,
147, 152.5, 158.8, 185.5.
3-(6,8-Dibromo-2-oxo-2H-chromen-3-yl)-1-phenyl-
1H-pyrazole-4-carbaldehyde (3e)
1
m.p.: 185–190 °C; H-NMR (DMSO, d, ppm): 7.39–8.26
(m, 8H), 8.279 (s, 1H), 9.92 (s, 1H).
1
photometer, FTLA 2000-100 model, using KBr pellets. H
NMR, was measured on a Brucker 300 MHz, spectrometer
using DMSO as a solvent and TMS as internal standard;
splitting patterns are as follows: s, singlet; d, doublet; and
m, multiplet (Chemical shifts in d ppm) mass spectra were
recorded on a Jeol JMSD-300 spectrometer.
3-(2-Oxo-2-H-benzo[g]chromen-3-yl)-1-phenyl-1H-
pyrazole-4-carbaldehyde (3f)
1
m.p.: 220–225 °C; H-NMR (DMSO, d, ppm): 7.59–8.42
(m, 12H), 9.27 (s, 1H), 9.92 (s, 1H).
General procedure for the synthesis of 3-(2-oxo-2H-
chromen-3-yl-)-1-phenyl-1H-pyrazole-4-carbaldehyde
(3a–f) derivatives
General procedure for the synthesis of 5-((3-(2-oxo-2H-
chromene-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)
pyrimidine-2,4,6(1H,3H,5H)-trione derivatives (4a–f)
To the cooled solution of DMF (1.0 mL,0.014 mol), POCl3
(1.3 mL, 0.014 mol) was added drop wise for half an hour
by maintaining the temperature at 0–5 °C. To this solution,
0.1 g (0.00031 mol) of derivatives of 3-(2-oxo-2H-chro-
men-3-yl-)-1-phenyl-1H-pyrazole-4-carbaldehyde (3a–f),
123

Med Chem Res
0.039 g (0.0003 mol) of BA and acetic acid (quantity)
were finely mixed together. The reaction mixture was
placed in a screw-capped vial and irradiated for 5–10 min
in a domestic microwave oven at 300 W. On cooling, solid
was separated out, which was filtered and recrystallized
from ethanol.
505. For the M.F C23H13BrN4O5, M.Wt 504. 13C-NMR
(DMSO, d, ppm): 116.4, 118.5, 119.3, 120.6, 121, 123.4,
127.9, 129.7, 131, 132.7, 134.9, 138.5, 141.7, 147, 152.5,
158.8, 161.2, 162.3.MS EIMS: m? 505. For the M.F C23H13
BrN4O5, M.wt 505.
5-((3-(6,8-Dibromo-2-oxo-2H-chromene-3-yl)-1-
phenyl-1H-pyrazol-4-yl)methylene)pyrimidine-
2,4,6(1H,3H,5H)-trione (4e)
5-((3-(2-Oxo-2H-chromene-3-yl)-1-phenyl-1H-
pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-
trione (4a)
m.p.: [300 °C; IR (KBr) (cm-1): 3283, 3102 (NH), 1733,
1704, 1667 (C=O), 1573 (C=N); 1H-NMR (DMSO, d,
ppm): 7.47–8.26 (m, 8H), 8.42 (s, 1H), 9.76 (s, 1H), 11.35
(s, 2H, 2NH). 13C-NMR (DMSO, d, ppm): 110.2, 114.7,
116.5, 119.6, 120.8, 121.7, 128.2, 129.9, 130.7, 134.6, 137,
138.3, 143.5, 149.7, 150.1, 152.7, 158.2, 162.5, 163.3,
165.3. MS EIMS: m ? 585. For the M.F C23H12Br2N4O5,
M.wt 585.
m.p.: [300 °C; IR (KBr) (cm-1): 3231, 3089 (NH), 1732,
1704, 1667 (C=O), 1573 (C=N); 1H-NMR (DMSO, d,
ppm): 7.44–8.5 (m, 10H), 9.27 (s, 1H), 9.77(s, 1H), 11.34
(s, 1H, NH), 11.36 (s, 1H, NH). 13C-NMR (DMSO, d,
ppm): 113.1, 114.5, 116.7, 116.8, 118, 119.9, 122.7, 126.5,
128.3, 128.8, 129.1, 130.1, 134.6, 138.6, 141.8, 143.5,
150.3, 152.8, 154, 159.5, 162.8, 163.2. MS EIMS:
m ? 426. For the M.F C23H14N4O5, M.wt 426.
5-((3-(2-Oxo-2H-benzo[g]chromene-3-yl)-1-phenyl-
1H-pyrazol-4-yl)methylene)pyrimidine-
2,4,6(1H,3H,5H)-trione (4f)
5-((3-(6-Chloro-2-oxo-2H-chromene-3-yl)-
1phenyl1Hpyrazol4yl)methylene)pyrimidine-
2,4,6(1H,3H,5H)-trione (4b)
m.p.: [300 °C; IR (KBr) (cm-1): 3270, 3089 (NH), 1730,
1701, 1665 (C=O), 1570 (C=N); 1H-NMR (DMSO, d,
ppm): 7.49–8.7 (m, 12H), 9.27 (s,1H), 9.81 (s, 1H), 11.3
(s, 1H, NH), 11.3 (s, 1H, NH). 13C-NMR (DMSO, d, ppm):
113.1, 114.5, 116.7, 116.8, 118, 119.9, 122.7, 126.5, 128.3,
128.8, 129.1, 130.1, 134.6, 138.6, 141.8, 143.5, 150.3,
152.8, 154, 158.5, 162.8, 163.6.
m.p.: [300 °C; IR (KBr) (cm-1): 3280,3100 (NH), 1730,
1704, 1665 (C=O), 1573 (C=N); 1H-NMR (DMSO, d,
ppm): 7.47–8.1 (m, 9H), 8.4 (s, 1H), 9.76 (s, 1H), 11.35
(s, 2H, 2NH).13C-NMR (DMSO, d, ppm): 114.5, 116.4,
118.3, 119.5, 120, 128, 128.1, 128.6, 129.9, 132.4, 134.5,
138.3, 143.2, 144, 150, 151.8, 152.3, 158.8, 162.5, 163.2.
MS ESI: m? 1 461. For the M.F C23H13ClN4O5, M.wt 460.
5-((3-(6,8-Dichloro-2-oxo-2H-chromene-3-yl)-1-
phenyl-1H-pyrazol-4-yl)methylene)pyrimidine2,4,6
(1H,3H,5H)-trione (4c)
General procedure for the synthesis of dihydro-5-((3-(2-
oxo-2H-chromene-3-yl)-1-phenyl-1H-pyrazol-4-
yl)methylene)2-thioxopyrimidine4,6(1H,5H)-diones
(5a–f).
m.p.: [300 °C; IR (KBr) (cm-1): 3279, 3920 (NH), 1733,
1702, 1662 (C=O), 1573 (C=N); 1H-NMR (DMSO, d,
ppm): 7.2–8.1 (m, 8H), 8.4 (s, 1H), 9.77 (s, 1H) 11.34
(s, 1H, NH), 11.34 (s, 1H, NH). 13C-NMR (DMSO, d, ppm)
114.5, 116.4, 118.3, 119.5, 120, 128, 128.1, 128.6, 129.9,
132.4, 134.5, 138.3, 143.2, 144, 150, 151.8, 152.3, 158.8,
162.2, 162.3.MS HRMS: m? 495, m? 1 496. For the M.F
C23H12Cl2N4O5, M.wt 495.
Derivatives of 3-(2-oxo-2H-chromen-3-yl-)-1-phenyl-1H-
pyrazole-4-carbaldehyde (3a–f) 0.1 g (0.00031 mol), TBA
0.0044 g (0.00031 mmol), and acetic acid were finely
mixed together and placed in a screw-capped vial and
irradiated for 5–10 min in a domestic microwave oven at
300 W power level. On cooling, solid was separated out,
which was filtered and recrystallized from ethanol.
5-((3-(6-Bromo-2-oxo-2H-chromene-3-yl)-1-
phenyl1Hpyrazol4yl)methylene)pyrimidine-
2,4,6(1H,3H,5H)-trione (4d)
Dihydro-5-(-((3-(2-oxo-2H-chromene-3-yl)-1-phenyl-
1H-pyrazol-4-yl)methylene)2-thioxopyrimidine4,6
(1H,5H)-dione (5a).
m.p.: [300 °C; IR (KBr) (cm-1): 3298, 3160 (NH), 1732,
1704, 1665 (C=O), 1572 (C=N); 1H-NMR (DMSO, d,
ppm): 7.38–8.6 (m, 9H), 9.2 (s, 1H), 9.68 (s, 1H), 11.34
(s, 1H, NH), 11.36 (s, 1H, NH). M S EIMS: 70 eV m? 1
m.p.: [300 °C; IR (KBr) (cm-1): 3229, 3093 (NH), 1732,
1704, (C=O), 1573 (C=N), 1292 (C=S); 1H-NMR (DMSO,
d, ppm): 7.44–8.51 (m, 10H), 9.7 (s, 1H), 9.80 (s, 1H), 11.3
(s, 1H, NH), 12.45 (s, 1H, NH). 13C-NMR (DMSO, d, ppm)
123

Med Chem Res
116.3, 118.7, 119.6, 125, 129.2, 129.9, 133, 134.5, 134.8,
138.5, 138.4, 144.3, 144.4, 145.6, 150.1, 152.4, 153.7,
159.3, 160.4, 161.6, 162.6, 163.4, 178.3. MS ESI: m? 1
443. For the M.F C23H14N4O4S, M.wt 442.
161.6, 178.3. MS ESI: m? 598. For the M.F C23H12
Br2N4O4S, M.wt 598.
Dihydro-5-((3-(2-oxo-benzo[g]chromene-3-yl)-
1-phenyl-1H-pyrazol-4yl)methylene)thioxopyrimidine-
4,6(1H,5H)-dione (5f)
5-((3-(6-Chloro-2-oxo-2H-chromene-3-yl)-1-
phenyl-1H-pyrazol-4-yl)methylene)-dihydro-
thioxopyrimidine-4,6(1H,5H)-dione (5b)
m.p.: [300 °C; IR (KBr) (cm-1): 3298, 3152 (NH), 1733,
1704 (C=O), 1570 (C=N), 1292 (C=S); H-NMR (DMSO,
1
m.p.: [300 °C; IR (KBr) (cm-1): 3260, 3082 (NH), 1730,
1705, (C=O), 1573 (C=N), 1294 (C=S); 1H-NMR (DMSO,
d, ppm): 7.2–8.13 (m, 9H), 8.44 (s, 1H), 9.79 (s, 1H), 11.1
(s, 1H, NH), 11.3 (s, 1H, NH). 13C-NMR (DMSO, d, ppm)
114.5, 116.4, 118.3, 119.5, 120, 128, 128.1, 128.6, 129.9,
132.4, 134.5, 138.3, 143.2, 144, 150, 151.8, 152.3, 158.8,
162.5, 162.7, 178.2. MS EIMS: m? 476. For the M.F
C23H13ClN4O4S, M.wt 476.
d, ppm): 7.51–8.7 (m, 12 H), 9.27 (s, 1H), 9.84 (s, 1H),
12.45 (s, 1H, NH), 12.46 (s, 1H, NH) 13C-NMR (DMSO, d,
ppm): 112.9, 114.4, 116.5, 116.9, 117.7, 119.7, 122.5,
126.3, 128.2, 128.6, 128.9, 129.9, 130, 134.4, 134.7, 138.4,
141.7, 144.4, 152.8, 153.9, 159.3, 160.4, 161.6, 178.3. MS
ESI: m? 1 493. For the M.F C27H16N4O4S, M.wt 492.
Acknowledgments The authors wish to thank Dr. U.S.N. Murthy,
Head, Biology division, Indian Institute of Chemical Technology,
Hyderabad, for screening the antimicrobial activity of the synthesized
compounds. The authors also thank Prof. D.S Keshava Rao for proof
reading and necessary language corrections. One of the authors S.V
thanks the Ministry of Human Resource Development for the
fellowship.
5-((3-(6,8-Dichloro-2-oxo-2H-chromene-3-yl)-1-
phenyl-1H-pyrazol-4-yl)methylene)-dihydro-
thioxopyrimidine-4,6(1H,5H)-dione (5c)
m.p.: [300 °C; IR (KBr) (cm-1): 3294, 3092 (NH), 1733,
1707, (C=O), 1573 (C=N), 1296 (C=S); 1H-NMR (DMSO,
d, ppm): 7.42–8.45 (m, 8H), 9.27 (s, 1H), 9.80 (s, 1H),
d = 12.46 (s, 1H, NH), d = 12.47 (s, 1H, NH). 13C-NMR
(DMSO, d, ppm): 114.7, 116.7, 118.3, 119.6, 119.9, 120,
128.1, 128.2, 129.9, 132.4, 138.2, 144.0, 144.3, 152.0,
152.3, 158.8, 160.3, 161.5, 178.3.
Conflict of interest The author reports no conflicts of interest. The
author alone hereby stands responsible for the contents of this sci-
entific paper.
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