Synthesis and antimicrobial evaluation of new 5-(2-hydroxyphenyl)-3-(4- (phenylthio)phenyl)-1 H -pyrazole-2(5 H)-carbothioamide analogues of 2-(4-(phenylthio)phenyl)-4 H -chromen-4-One

Article abstract of DOI:10.1080/10426507.2011.610850

A series of novel 5-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)-1H-pyrazole- 2(5H)-carbothioamide derivatives have been synthesized via the ring opening of 2-(4-(phenylthio)phenyl)-4H-chromen-4-one with semicarbazide in ethanol and KOH under ultrasonic irradiation. The synthesized compounds were screened for antibacterial and antifungal activity against bacteria Staphylococcus aureus (MRSA E710) and Escherichia coli (25922) and fungi Candida albicans and Aspergillus fumigates, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, ¹H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Biological Assay.

Full text of DOI:10.1080/10426507.2011.610850

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Synthesis and Antimicrobial Evaluation
of New 5-(2-Hydroxyphenyl)-3-(4-
(Phenylthio)Phenyl)-1H-Pyrazole-2(5H)-
Carbothioamide Analogues of 2-(4-
(Phenylthio)Phenyl)-4H-Chromen-4-One
Asha V. Chate a , Ratnadeep S. Joshi a , Priyanka G. Mandhane a ,
Shweta R. Mohekar b & Charansingh H. Gill a
a Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada
University, Aurangabad, India
b Y. B. Pharmacy College, Maulana Azad campus, Auranagabad, India
Version of record first published: 31 Jan 2012.
To cite this article: Asha V. Chate, Ratnadeep S. Joshi, Priyanka G. Mandhane, Shweta R. Mohekar
& Charansingh H. Gill (2012): Synthesis and Antimicrobial Evaluation of New 5-(2-Hydroxyphenyl)-3-
(4-(Phenylthio)Phenyl)-1H-Pyrazole-2(5H)-Carbothioamide Analogues of 2-(4-(Phenylthio)Phenyl)-4H-
Chromen-4-One, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:3, 327-335
To link to this article: http://dx.doi.org/10.1080/10426507.2011.610850
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Phosphorus, Sulfur, and Silicon, 187:327–335, 2012
Copyright ꢀC Al Azhar University of Gaza
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.610850
SYNTHESIS AND ANTIMICROBIAL EVALUATION OF NEW
5-(2-HYDROXYPHENYL)-3-(4-(PHENYLTHIO)PHENYL)-1H-
PYRAZOLE-2(5H)-CARBOTHIOAMIDE ANALOGUES OF
2-(4-(PHENYLTHIO)PHENYL)-4H-CHROMEN-4-ONE
Asha V. Chate,1 Ratnadeep S. Joshi,1 Priyanka G. Mandhane,1
Shweta R. Mohekar,2 and Charansingh H. Gill1
1Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad, India
2Y. B. Pharmacy College, Maulana Azad campus, Auranagabad, India
GRAPHICAL ABSTRACT
R1
R2
R3
OH
O
R1
F
S
R2
R3
OH
O
S
SH
4 (a-g)
I
II
CHO
CHO
1
2
3
5 (a-g)
4a,5a: R1=H;R2=H;R3=H
4b,5b: R1=Cl;R2=H;R3=Cl
4c,5c: R1=CH3;R2=H;R3=CH3
4d,5d: R1=H;R2=CH3;R3=Cl
III
R1
R2
R3
OH
S
S
R1
R2
R3
O
4e,5e:
R1=H;R2=H;R3=Cl
IV
4f,5f: R1=H;R2=H;R3=F
4g,5g: R1=H;R2=H;R3=CH3
N
N
S
O
H2N
6 (a-g)
7 (a-g)
Abstract A series of novel 5-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)-1H-pyrazole-
2(5H)-carbothioamide derivatives have been synthesized via the ring opening of
2-(4-(phenylthio)phenyl)-4H-chromen-4-one with semicarbazide in ethanol and KOH under
ultrasonic irradiation. The synthesized compounds were screened for antibacterial and
antifungal activity against bacteria Staphylococcus aureus (MRSA E710) and Escherichia
coli (25922) and fungi Candida albicans and Aspergillus fumigates, respectively. Some of the
tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data,
and elemental analysis elucidated the structures of all the newly synthesized compounds.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
resource: Biological Assay.
Keywords Pyrazoles; chromones; chalcones; antibacterial activity; antifungal activity
Received 22 June 2011; accepted 26 July 2011.
The authors are grateful to the Head, Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada
University, Aurangabad for providing the laboratory facility. The authors are also thankful to the Director, SAIF,
Punjab University, Chandigarh for spectral analysis of novel compounds and Y. B. Pharmacy College, Maulana
Azad campus, Auranagabad for Biological Screening.
Address correspondence to Charansingh H. Gill, Department of Chemistry, Dr. Babasaheb Ambedkar
Marathwada University, Aurangabad 431004, India. E-mail: chgill16@gmail.com
327

328
A. V. CHATE ET AL.
INTRODUCTION
Pyrazoles have a broad spectrum of biological and pharmaceutical properties such
as antimicrobial, antihypertensive, antitumor, anti-inflammatory, antidepressant, and an-
ticonvulsant activities.1–4 It was recently reported that 1-thiocarbamoyl-2-pyrazolines are
cholinesterase5 and selective monoamine5–7 inhibitors that may have promising features in
the treatment of Parkinson’s and Alzeheimer’s diseases. They are also useful intermediates
for important pharmaceutical products, such as rimonabant8 and celecoxib.9
A literature survey shows that organosulfur compounds are biologically active and
some find commercial application as fungicides and bactericides.10–13 However, their bi-
ological activity is dependent not only on the presence of sulfur, but also often on the
presence of additional activating groups. In biological processes, the thiol group is of par-
ticular interest because of its involvement in the mechanism of a number of hormones,
enzymes, and other biologically active proteins.14 They act as antioxidants by scavenging
radicals via hydrogen abstraction,15 as well as one-electron oxidation.16 Indeed, thiols are
generally regarded as repair agents for the oxidative damage site in natural cells such as
DNA, lipids, proteins, and carbohydrates,17 so they have been subject of various studies.18
Therefore, in view of these important biological activities of both, and in continuation
of our research program,19–23 we report the synthesis of some new thiophenol-incorporated
pyrazole derivatives, from the analogues of 2-(4-(phenylthio)phenyl)-4H-chromen-4-one
and test the antibacterial and antifungal activities of the new resulting compounds against
representative Gram-negative and Gram-positive bacteria and fungi, which have been found
to possess an interesting profile of pharmacological activity.
RESULT AND DISCUSSION
Chemistry
The synthetic route for the preparation of (E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)
phenyl)-1H-pyrazole-1-carbothioamide analogues of 2-(4-(phenylthio)phenyl)-4H-
chromen-4-one are shown in Scheme 1. Thiophenol (1) was treated with
R1
R2
R3
OH
O
R1
R2
R3
OH
O
S
S
F
SH
K2CO3/DMF
reflux 120O
4 (a-g)
C
EtOH/KOH, )))))
CHO
CHO
1
2
3
5 (a-g)
4a,5a: R1=H;R2=H;R3=H
4b,5b: R1=Cl;R2=H;R3=Cl
4c,5c: R1=CH3;R2=H;R3=CH3
4d,5d: R1=H;R2=CH3;R3=Cl
DMSO/I2,
reflux 120O
C
S
R1
O
R1
4e,5e:
R1=H;R2=H;R3=Cl
R2
R3
OH
N
S
R2
R3
O
4f,5f: R1=H;R2=H;R3=F
4g,5g: R1=H;R2=H;R3=CH3
NH2CNHNH2
KOH/EtOH,
))))))), 65O
C
N
O
S
6 (a-g)
H2N
7 (a-g)
Scheme 1

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF ANALOGUES CHROMONES
329
4-flurobenzaldehyde (2) in DMF and K2CO3 at 120 ◦C to yield 4-(phenylthio)benzaldehyde
(3). The 4-(phenylthio)benzaldehyde (3) was subjected to a base-catalyzed Claisen-
Schmidt condention reaction24 with appropriate o-hydroxy acetophenones 4(a–g)
generating (E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio) phenyl)prop-2-en-1-one 5(a–g).
2-(4-(phenylthio)phenyl)-4H-chromen-4-one 6(a–g) were prepared by the oxidative
cyclization of corresponding (E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-
en-1-one 5(a–g) in dimethyl sulfoxide and a catalytic amount of iodine at 120 ◦C.
The compounds 6(a–g), on treatment with semicarbazide in ethanol (EtOH)
and potassium hydroxide under ultrasonication, yielded (E)-1-(2-hydroxyphenyl)-3-(4-
(phenylthio) phenyl)-1H-pyrazole-1-carbothioamide 7(a–g). In order to obtain the
optimum experimental conditions, the reaction of (E)-1-(2-hydroxyphenyl)-3-(4-
(phenylthio)phenyl)-1H-pyrazole-1-carbothioamide under ultrasonic irradiation has been
considered as a model reaction. The ultrasonic irradiation plays an important role in
the synthesis of (E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one and
(E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbothioamide, and
the reaction rate improved in a short time span. To determine the appropriate time of
the reaction, we investigated the model reaction at different times (20, 25, 30, 35, 40,
45, 50, 55 min). The product was formed in lower yield at 20–45 min, and higher at
55–58 min. This indicates that 56 min was sufficient for the result. The reaction yield was
improved under sonication at appropriate temperature. The best yield for ◦7a was obtained
by ultrasonic (nominal power 200 W) irradiation at a temperature of 65 C. The product
that was obtained within 56 min gives bette◦r yield. In conventional method, the yield
7a gained 47% after heating for 5–6 h at 65 C. It was observed that the reaction under
ultrasonic irradiation had significantly improved yields. The purity of compounds was
checked by TLC.
Spectral Analysis
Analytical and spectral data (IR, 1H NMR, and mass and elemental analysis) of the
newly synthesized compounds were in full agreement with the proposed structures. The
structure of 5a is interpreted from spectroscopic data. The IR spectrum of 5a showed a
characteristic absorption band at 3200 cm−1 due to OH stretching. Its 1H NMR spectrum
exhibited the presence of olefinic protons as a doublet at δ = 6.98 and 7.96 regions with
a mutual coupling constant value (J = 14.30 & 14.41 Hz). These observed coupling
constant values indicate the presence of the E,Eꢀ-configuration that form the structure, and
the remaining aromatic protons appear at their respective positions. The phenolic OH
is highly deshielded and appears at δ = 12.73 ppm. The mass spectrum of (E)-1-(2-
hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one showed (M+) peak at 333.15.
The IR spectra of prepared 6a revealed the disappearance of the respective OH stretching
absorption due to ring cyclization and also showed a characteristic absorption band at
1
1600 cm−1 and 1645 cm−1, respectively due to C O stretching. The H NMR spectrum
of 6a revealed the characteristic CH2 proton of the chromone ring appearing at δ = 6.98
ppm as a singlet and the rest of the aromatic protons appear at their respective positions.
The mass spectrum of 2-(4-(phenylthio)phenyl)-4H-chromen-4-one showed (M+) peak at
331.09. The IR spectrum of 7c showed a characteristic absorption band at 3428 cm−1 due
to OH stretching and the bands at 1500–1600 cm−1 and 1649–1670 cm−1 correspond to
C N and C O stretching, respectively. Its 1H NMR spectrum exhibited two singlets at
δ = 2.27 and 2.58 ppm characteristic of two CH3 protons, respectively, and, in turn, the

330
A. V. CHATE ET AL.
pyrazol proton (H-4) at δ = 6.51 and the NH2 proton of the carbonyl group were found at
δ = 6.68 ppm as a broadband and also showed one singlet at δ = 9.80 ppm of OH due to
ring opening of chromone. The mass spectrum of 7c showed (M+) peak at 416.12. Figures
S1–S6 (Supplemental Materials) show sample spectra for compounds 5b, 6b, 7b, 5d, 6d,
and 7d.
CONCLUSION
In summary, we have synthesized the series of sulfur-incorporated novel sub-
stituted (E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one and (E)-1-(2-
hydroxyphenyl)-3-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbothioamide derivatives and
have evaulated their antimicrobial activities. All the compounds demonstrated potent in-
hibition against all the tested strains. The importance of such work lies in the possibility
that the new compounds might be more efficacious drugs against bacteria and fungi, which
could be helpful in designing more potent antibacterial and antifungal agents for therapeutic
use. The structures of the synthesized compounds were confirmed with their spectral data.
EXPERIMENTAL
The melting points of all synthesized compounds were determined in open capillary
tubes and were uncorrected. The purity of all compounds was checked by TLC. IR spectra
1
were recorded on Jasco FT-IR-4100, Japan, in KBr disc, H NMR spectra were recorded
on a Varian AS 400 MHz spectrometer in CDCl3/DMSO-d6; chemical shifts (δ) are in ppm
relative to tetramethylsilane and coupling constants (J) are expressed in hertz (Hz). Mass
spectra were recorded on a Macro mass spectrometer (Water) by the electro-spray method
(ES). Elemental analysis was performed on Perkin-Elmer EAL-240 elemental analyzer.
Bandelin Sonorex (with a frequency of 35 kHz and a nominal power 200 W) ultrasonic
bath was used for ultrasonic irradiation. Built-in heating at 30–80 ◦C are thermostatically
adjustable. The reaction vessel was placed inside the ultrasonic bath containing water.
General Procedure for the Synthesis of (E)-1-(2-hydroxyphenyl)-3-
(4-(phenylthio)phenyl)prop-2-en-1-one 5(a–g)
Aqueous KOH (0.03 mol) was added to a suspension of o-hydroxyacetophenone
(0.01 mol) and 4-(phenylthio)benzaldehyde (0.01 mol) in EtOH (15 mL). The mixture was
irradiated under ultrasonication (nominal power 200 W) for 4–5 h; completion of reaction
was monitored by TLC. Furthermore, the reaction mass was poured over crushed ice and
acidified with (2N) HCl until pH was reduced. The yellow solid thus obtained was filtered,
washed with water, and dried. Then, the residue was purified by crystallization to afford
5(a–g).
(E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one (5a): Yield:
80% (yellow solid); mp 89–93 ◦C; IR (KBr) cm−1: 3219( OH), 1643 (C O), 1571, 1484;
1H NMR (400 MHz, DMSO): δ 6.98 (d, J = 14.3 Hz, 1H, -olefinic-H), 7.53 (t, 1H, Ar-H),
7.06–7.67 (m, 10H, Ar-H), 7.67 (t, 1H, Ar-H), 7.96 (d, J = 14.41Hz, 1H, -olefinic-H), 7.99
(d, 1H, Ar-H), 12.73 (s, 1H, OH); EC–MS: 333.15 (M+); Anal. Calcd. for C21H16O2S: C,
75.88%, H: 4.85%,S: 9.65%; Found: C: 75.72%, H: 4.71%: S: 9.58%.
(E)-1-(3,5-dichloro-2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one
◦
(5b): Yield: 85% (yellow solid); mp 121–123 C; IR (KBr) cm−1: 3256 ( OH), 1642

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF ANALOGUES CHROMONES
331
1
(C O), 1549, 1488; H NMR (400 MHz, CDCl3): δ 6.93 (dd, 1H, Ar-H), 6.95 (d, 1H,
Ar-H), 7.10 (d, 1H, Ar-H), 7.14 (d, 1H, Ar-H), 7.26 (d, 1H, Ar-H), 7.31–7.69 (m, 5H,
Ar-H), 7.95 (d, J = 15.64, Olefinic H), 8.03 (d, J = 14.76, Olefinic H), 12.64 (s, 1H,
OH).; EC–MS: 401.03 (M+); Anal. Calcd. for C21H14Cl2O2S: C: 62.86%, H: 3.54%, S:
8.01%; Found: C: 62.91%, H: 3.63%, S: 8.11%.
(E)-1-(2-hydroxy-3,5-dimethylphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one
(5c): Yield: 78% (yellow solid); mp 78–80 ◦C; IR (KBr) cm−1: 3269 ( OH), 1640 (C O),
1571, 1478; 1H NMR (400 MHz, CDCl3): δ 2.39 (s, 3H, CH3), 2.19 (s, 3H, CH3), 7.29 (d,
J = 14.87 Hz, 1H, -olefinic-H), 7.30–7.62 (m, 9H, Ar-H), 7.23–7.28 (d, 2H, Ar-H), 7.95
(d, J = 14.90 Hz, 1H, -olefinic-H), 12.20 (s, 1H, OH); EC–MS: 361.14 (M+); Anal.
Calcd. for C23H20O2S: C: 76.64%, H: 5.59%, S: 8.90%; Found: C: 76.76%, H: 5.65%, S:
8.95%.
(E)-1-(5-chloro-2-hydroxy-4-methylphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-
◦
1-one (5d): Yield: 88% (yellow solid); mp 113–115 C; IR (KBr) cm−1: 3301 ( OH),
1
1631 (C O), 1579, 1496; H NMR (400 MHz, CDCl3): δ 2.45 (s, 3H, CH3), 6.93 (s,
1H, Ar-H), 7.05 (d, J = 12.98 Hz, 1H, olifinic-H), 7.08–7.59 (m, 9H, Ar-H), 7.56 (s, 1H,
Ar-H), 7.92 (d, J = 13.01 Hz, 1H, olifinic-H), 12.73 (s, 1H, OH); EC–MS: 381.04 (M+)
& 382.13 (M+2); Anal. Calcd. for C22H17ClO2S: C: 69.37%, H: 4.50%, S: 8.42%; Found:
C: 69.24%, H: 4.42%, S: 8.34%.
(E)-1-(2-hydroxy-5-methylphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one (5e):
Yield: 86% (yellow solid); mp 92–94 ◦C; IR (KBr) cm−1: 3243 ( OH), 1630 (C O), 1569,
1496; 1H NMR (400 MHz, CDCl3): δ 6.98 (d, J = 15.12 Hz, 1H, -olefinic-H), 7.12–7.31
(m, 10H, Ar-H), 7.51–7.68 (d, 2H, Ar-H), 7.98 (d, J = 15.18 Hz, 1H, -olefinic-H), 12.29
(s, 1H, OH); EC–MS: 367.03 (M+) & 369.12 (M+2); Anal. Calcd. for C21H15ClO2S: C:
68.75%, H: 4.12%, S: 8.74%; Found: C: 68.64%, H: 4.08%, S: 8.65%.
(E)-1-(5-fluoro-2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one (5f):
Yield: 82% (yellow solid); mp 72–74 ◦C; IR (KBr) cm−1: 3208 ( OH), 1634 (C O), 1570,
1498; 1H NMR (400 MHz, CDCl3): δ 6.94 (d, J = 14.84 Hz, 1H, -olefinic-H), 7.09–7.34
(m, 10H, Ar-H), 7.58-7.71 (d, 2H, Ar-H), 8.01(d, J = 14.88 Hz, 1H, -olefinic-H), 12.31 (s,
1H, OH); EC–MS: 351.21 (M+); Anal. Calcd. for C21H15FO2S: C: 71.98%, H: 4.32%,
S: 9.16%; Found: C: 72.01%, H: 4.42%, S: 9.29%.
(E)-1-(2-hydroxy-3,5-methylphenyl)-3◦-(4-(phenylthio)phenyl)prop-2-en-1-one
(5g): Yield: 79% (yellow solid); mp 68–70 C; IR (KBr) cm−1: 3234 ( OH), 1632
1
(C O), 1569, 1487; H NMR (400 MHz, DMSO): δ 2.40 (s, 3H, CH3), 6.84 (d, J =
14.53, 1H, -olefinic-H), 7.05–7.24 (m, 10H, Ar-H), 7.48–7.61 (d, 2H, Ar-H), 7.93 (d,
J = 14.61, 1H, -olefinic-H), 12.23 (s, 1H, OH); EC–MS: 342.11(M+); Anal. Calcd.
for C22H18O2S: C: 76.27%, H: 5.24%, S: 9.26%; Found: C: 76.16%, H: 5.13%, S:
9.12%.
General Procedure for the Synthesis of 2-(4-(phenylthio)phenyl)-
4H-chromen-4-one 6(a–g)
Chalcone (0.003 mol) was dissolved in 15 mL of DMSO and to this reaction mixture
a catalytic amount of iodine was added. The reaction mixture was heated in an oil bath
for 2 h at 120 ◦C. The reaction was monitored by TLC. After completion of the reaction,
the reaction mixture was cooled and then 20 mL of cold water was slowly added to the
flask and the separated product was filtered, washed with water by dil. sodium thiosulphate

332
A. V. CHATE ET AL.
solution for several times, and dried under vacuum and crystallized from EtOH to afford
6(a–g).
2-(4-(phenylthio)phenyl)-4H-chromen-4-one (6a): Yield: 72% (brown solid); mp
106–108 ◦C; IR (KBr) cm−1: 1620 (C O), 1465, 1377, 770; 1H NMR (400 MHz, CDCl3):
δ 6.96–7.04 (m, 4H, Ar-H), 6.98 (s, 1H, Ar-H), 7.07 (t, 1H, Ar-H), 7.16 (d, 2H, Ar-H),
7.21–7.68 (m, 5H, Ar-H), 7.41 (t, 1H, Ar-H); EC–MS: 331.09 (M+); Anal. Calcd. for
C21H14O2S: C: 69.13, H: 3.59, S: 8.79%; Found: C: 69.18%, H: 3.61%, S: 8.84%.
6,8-dichloro-2-(4-(phenylthio)phenyl)-4H-chromen-4-one (6b): Yield: 79% (brown
solid); mp 138–140 ◦C; IR (KBr) cm−1: 1635 (C O), 1574, 1495 (C C); 1H NMR (400
MHz, DMSO): δ 6.73 (s, 1H, Ar-H), 7.28 (d, 1H, Ar-H), 7.30–7.55 (m, 9H, Ar-H), 7.75
(d, 1H, Ar-H); EC–MS: 365.01 (M+) & 367.11 (M+2); Anal. Calcd. for C21H12Cl2O2S: C:
58.15%, H: 2.56%, S: 7.39%; Found: C: 58.23%, H: 2.63%, S: 7.43%.
6,8-dimethyl-2-◦(4-(phenylthio)phenyl)-4H-chromen-4-one (6c): Yield: 79% (brown
1
solid); mp 145–147 C; IR (KBr) cm−1: 1636 (C O), 1574, 1491 (C C); H NMR
(400 MHz, CDCl3): δ 2.18 (s, 3H, CH3), 2.35 (s, 3H, CH3), 6.68–6.91 (s, 2H, Ar-H),
7.04–7.37 (m, 7H, Ar-H), 7.23–7.29 (d, 3H, Ar-H); EC–MS: 385.10 (M+); Anal. Calcd.
for C23H18O2S: C: 70.31, H: 4.36%, S: 8.16%; Found: C: 70.36%, H: 4.44%, S: 8.21%.
6-chloro-7-methyl-2-(4-(phenylthio)phenyl)-4H-chromen-4-one (6d): Yield: 81%
(brown solid); mp 210–212 ◦C; IR (KBr) cm−1: 1623 (C O), 1571, 1493 (C C); 1H NMR
(400 MHz, CDCl3): δ 2.50 (s, 3H, CH3), 6.73 (s, 1H, Ar-H), 7.26 (s, 1H, Ar-H), 7.29–7.88
(m, 9H, Ar-H), 7.79 (s, 1H, Ar-H); EC–MS: 413.16 (M+) & 415.02 (M+2); Anal. Calcd.
for C22H15ClO2S: C: 63.93%, H: 3.41%, S: 7.76%; Found: C: 63.99%, H: 3.50%, S: 7.81%.
6-chloro-2-(4-(phenylthio)phenyl)-4H-chromen-4-one (6e): Yield: 80% (brown
◦
1
solid); mp 110–113 C; IR (KBr) cm−1: 1633 (C O), 1571, 1493 (C C); H NMR
(400 MHz, CDCl3): δ 6.79 (s, 1H, Ar-H), 6.88 (d, 1H, Ar-H), 6.98–7.14 (m, 8H, Ar-H),
7.42–7.51 (d, 3H, Ar-H); EC–MS: 359.07 (M+); Anal. Calcd. for C21H13ClO2S: C: 63.17%,
H: 3.01%, S: 8.04%; Found: C: 63.24%, H: 3.11%, S: 8.12%.
6-fluoro-2-(4-(phenylthio)phenyl)-4H-chromen-4-one (6f): Yield: 70% (brown
solid); mp 123–125 ◦C; IR (KBr) cm−1: 1642 (C O), 1579, 1489 (C C); 1H NMR (400
MHz, CDCl3): δ 6.89 (d, 1H, Ar-H), 6.99 (s, 1H, Ar-H), 7.13 (d, 1H, Ar-H). 7.20–7.42 (m,
9H, Ar-H), 7.31 (d, 1H, Ar-H); EC–MS: 345.12 (M+); Anal. Calcd. for C21H13FO2S: C:
65.88%, H: 3.16%, S: 8.38%; Found: C: 65.91%, H: 3.19%, S: 8.41%.
6-methyl-2-(4-(◦phenylthio)phenyl)-4H-chromen-4-one (6g): Yield: 69% (brown
1
solid); mp 103–105 C; IR (KBr) cm−1: 1612 (C O), 1565, 1490 (C C); H NMR
(400 MHz, DMSO): δ 2.46 (s, 3H, CH3), 6.91 (d, 1H, Ar-H), 6.96 (s, 1H, Ar-H), 7.05–7.19
(m, 9H, Ar-H), 7.07 (d, 1H, Ar-H), 7.44 (d, 1H, Ar-H); EC–MS: 398.98 (M+) & 400.01
(M+2); Anal. Calcd. for C22H16O2S: C: 69.74%, H: 3.99%, S: 8.59%. Found: C: 69.79%,
H: 4.03%, S: 8.51%.
General Procedure for the Synthesis of (E)-1-(2-hydroxyphenyl)-
3-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbothioamide 7(a–g)
Aqueous KOH (0.0015 mol) was added to a suspension of 2-(4-(phenylthio)phenyl)-
4H-chromen-4-one (0.0015 mol) and semicarbazide (0.0015 mol) in 10 mL EtOH. The
mixture was irradiated under ultrasonication (nominal power 200 W) for 56 min at 65 ◦C;
completion of reaction was monitored by TLC. Furthermore, the reaction mass was poured
over crushed ice and acidified with (2N) HCl until pH was reduced. The solid was filtered,

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF ANALOGUES CHROMONES
333
washed with water, and dried. Then, the residue was purified by crystallization to afford
7(a–g).
(E)-1-(2-hydroxyphenyl)-5-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbothioamide
◦
(7a): Yield: 70% (cream color solid); mp 206–208 C; IR (KBr): (cm−1) 3481 (N H),
1
1576 (C N), 1501 (C C), 1649 (C O); H NMR (400 MHz; DMSO-d6): δ 6.05 (s,
2H, CONH2), 7.01 (s, 1H, Pyrazoline C4-H), 7.05–7.51(m, 13H, Ar-H), 12.70 (s, 1H,
OH); ES–MI (m/z) 388.03 (M+). Anal. Calcd. for C22H17N3O2S: C: 68.20%, H: 4.42%,
N:10.85%, S: 8.28.%. Found: C: 68.12%, H: 4.51%, N: 10.75%, S: 8.34%.
3-(3,5-dichloro-2-hydroxyphenyl)-5-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbo
thioamide (7b): Yield: 67% (white solid); mp 125–127 ◦C; IR (KBr): (cm−1) 3392 (N H),
1580 (C N), 1518 (C C), 1676 (C O); 1H NMR (400 MHz; CDCl3-d6): δ 5.32 (s, 2H,
CONH2), 6.89 (s, 1H, Pyrazoline C4-H), 7.10–8.10 (m, 9H, Ar-H), 7.54 (d, 1H, Ar-H),
7.74 (d, 1H, Ar-H), 12.67 (s, 1H, OH); ES-MI (m/z) 456.01 (M+) & 458.06 (M+2).
Anal. Calcd. for C22H15Cl2N3O2S: C: 57.90%, H:3.31%, N: 9.21%,S: 7.03.%. Found: C:
57.58%, H: 3.13%, N: 9.11%, S: 6.89%.
3-(2-hydroxy-3,5-dimethylphenyl)-5-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbo
thioamide (7c): Yield: 65% (cream color solid); mp 210–213 ◦C; IR (KBr): (cm−1
)
1
3444–3233 (N H), 1586 (C N), 1511 (C C), 1676 (C O); H NMR (400 MHz;
DMSO-d6): δ 2.27 (s, 3H, CH3), 2.58 (s, 3H, CH3), 6.68 (s, 2H, CONH2), 6.51 (s, 1H,
Pyrazolines C4-H), 6.82 (d, 1H, Ar-H), 7.03 (d, 1H, Ar-H), 7.19–7.51 (m, 9H, Ar-H),
12.80 (s, 1H, OH); ES–MI (m/z) 416.12 (M+). Anal. Calcd. for C24H21N3O2S: C: 69.37,
H:5.09, N: 10.11, S: 7.72%. Found: C: 69.23, H: 4.96, N: 10.01, S : 7.67%.
3-(5-dichloro-2-hydroxy-4-methylphenyl)-5-(4-(phenylthio)phenyl)-1H-pyrazole-
◦
1-carbothioamide (7d): Yield: 72% (orange solid); mp 186–189 C; IR (KBr): (cm−1
)
3423 (N H), 1588 (C N), 1503 (C C), 1674 (C O); 1H NMR (400 MHz; CDCl3-d6):
δ 2.17 (s, 3H, CH3), 5.10 (s, 2H, CONH2), 6.47 (s, 1H, Ar-H), 6.47–6.48 (m, 3H, Ar-H),
7.26 (s, 1H, Pyrazolines C4-H), 7.39 (s, 1H, Ar-H), 7.65–7.91 (m, 6H, Ar-H), 12.67 (s,
1H, OH); ES–MI (m/z) 436.12 (M+) & 438.07 (M+2). Anal. Calcd. for C23H18ClN3O2S:
C: 63.37%, H: 4.16%, N: 9.64%, S:7.36%. Found: C: 63.25%, H: 4.07%, N: 9.54%, S:
7.24%.
3-(5-chloro-2-hydroxyphenyl)-5-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbothio
◦
amide (7e): Yield: 69% (orange solid); mp 155–157 C; IR (KBr): (cm−1) 3388 (N H),
1
1576 (C N), 1500 (C C), 1656 (C O); H NMR (400 MHz; CDCl3-d6): δ 5.59 (s,
2H, CONH2), 6.54 (s, 1H, Pyrazolines C4-H), 6.79 (d, 1H, Ar-H), 7.05 (dd, 1H, Ar-H),
7.08–7.32 (m, 9H, Ar-H), 7.37 (d, 1H, Ar-H), 12.65 (s, 1H, OH); ES–MI (m/z) 422.09
(M+) & 424.11 (M+2). Anal. Calcd. for C22H16ClN3O2S: C: 62.63%, H: 3.82%, N: 9.96%,
S: 7.60%. Found: C: 62.51%, H: 3.71%, N: 9.86%, S: 7.52%.
3-(5-fluoro-2-hydroxyphenyl)-5-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbothio
◦
amide (7f): Yield: 72% (cream color solid); mp 164–166 C; IR (KBr): (cm−1) 3477
(N H), 1575 (C N), 1507 (C C), 1365 (C O); 1H NMR (400 MHz; CDCl3-d6): δ 5.92
(s, 2H, CONH2), 6.74 (d, 1H, Ar-H), 6.96 (s, 1H, Pyrazolines C4-H), 7.00 (d, 1H, Ar-H),
7.07–7.45 (m, 9H, Ar-H), 7.79 (dd, 1H, Ar-H), 12.78 (s, 1H, OH); ES–MI (m/z) 406.13
(M+). Anal. Calcd. for C22H16FN3O2S: C: 65.17%, H: 3.98%, N: 10.36%, S:7.91%.
Found: C: 65.03%, H: 3.85%, N: 10.23%, S: 7.86%.
3-(2-hydroxy-5-methylphenyl)-5-(4-(phenylthio)phenyl)-1H-pyrazole-1-carbothio
◦
amide (7g): Yield: 62% (brown solid); mp 144–146 C; IR (KBr): (cm−1) 3444 (N H),
1586 (C N), 1503 (C C), 1376 (C O); 1H NMR (400 MHz; CDCl3-d6): δ 2.47 (s, 3H,
CH3), 5.88 (s, 2H, CONH2), 6.68 (d, 1H, Ar-H), 6.79 (d, 1H, Ar-H), 6.90 (dd, 1H, Ar-H),

334
A. V. CHATE ET AL.
6.92 (s, 1H, Pyrazolines C4-H), 7.13–7.59 (m, 9H, Ar-H), 12.88 (s, 1H, OH); ES–MI (m/z)
401.13 (M+). Anal. Calcd. for C23H19N3O2S: C: 68.81%, H: 4.77%, N: 10.47%, S: 7.99%.
Found: C: 68.72%, H: 4.63%, N: 10.37%, S: 7.89%.
Antimicrobial Activity
The standardized agar well diffusion method25 was followed to determine the activ-
ity of the synthesized compounds against the sensitive organisms Staphylococcus aureus
(MRSA E710) and Escherichia coli (25922) as a Gram-positive bacteria, and two species
of fungi, Candida albicans and Aspergillus fumigates. Vancomycin was used as reference in
the case of antibacterial, while Amphotericin B was used in the case of antifungal reference.
Methanol was used as solvent control. Experimental details and tabular results of biological
testing are found in the Supplemental Materials (Table S1).
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