Ultrasound-Assisted Facile Synthesis and Antimicrobial Studies of Alkanediyl-bis-thiazolidin-4-ones and Alkanediyl-bis-thiazinan-4-ones

Article abstract of DOI:10.1002/jhet.3590

Alkanediyl-bis-2-aryl-thiazolidin-4-one and alkanediyl-bis-2-aryl-1,3-thiazinan-4-one derivatives have been congregated in a single step reaction of diaminoalkanes, aryl aldehydes, and sulfanyl acids in the presence of coupling agent N,N′-dicyclohexylcarb

Full text of DOI:10.1002/jhet.3590

Month 2019
Ultrasound-Assisted Facile Synthesis and Antimicrobial Studies of
Alkanediyl-bis-thiazolidin-4-ones and Alkanediyl-bis-thiazinan-4-ones
a
b
a
b
a
*
Amritpal Kaur, Avneet Pal Kaur, Poonam Gautam, Deepika Gautam, and Ram Pal Chaudhary
aDepartment of Chemistry, Sant Longowal Institute of Engineering and Technology, Longowal, (Sangrur)
Punjab-148106, India
bDepartment of Chemistry, Sant Baba Bhag Singh University, Jalandhar, Punjab 144030, India
*E-mail: rpchaudhary65@gmail.com
Received October 4, 2018
DOI 10.1002/jhet.3590
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
Alkanediyl-bis-2-aryl-thiazolidin-4-one and alkanediyl-bis-2-aryl-1,3-thiazinan-4-one derivatives have
been congregated in a single step reaction of diaminoalkanes, aryl aldehydes, and sulfanyl acids in the pres-
ence of coupling agent N,N0-dicyclohexylcarbodiimide under ultrasonic conditions. This method of con-
structing 4-keto derivatives of thiazolidine and thiazinane is quick and clean besides yielding the products
in quantitative yields. The spectral techniques corroborated the structures of the isolated products. Biological
assay of the synthesized products has also been reported.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
studies of some alkanediyl-bis-2-arylthiazolidin-4-ones
and alkanediyl-bis-2-aryl-1,3-thiazinan-4-one derivatives.
Heterocyclic compounds deserve significant attention
and utility in pharmaceutical and materials field because
of their strong ability to exhibit various activities. The
heterocyclic nuclei have notable potential to function as
both biomimetics and active pharmacophores. Various
heterocyclic motifs have made a huge contribution
toward the development of numerous biologically active
compounds. Among them, the thiazolidine nucleus occurs
frequently in the structure of various natural products,
notably thiamine, compounds possessing cardiac and
glycemic advantages such as troglitazone [1], and many
metabolic products of fungi and ancient marine animals.
Pioglitazone [2] and rosiglitazone are therapeutic
agents for the treatment of diabetes. 1,3-Thiazolidin-4-
ones and 1,3-thiazinan-4-ones have been exploited in
the recent past for their wide range of biological
activities such as antifungal [3], anticonvulsant [4], anti-
HIV [5], analgesic [6], antiurease [7], antiviral [8],
trypanocidal [9], antibacterial [10], anticancer [11], anti-
inflammatory [12,13], cytotoxic [14], antitumor [15], and
antituberculotic [16] activities. They also have potential
for treating diabetic complications such as nephropathy,
RESULT AND DISCUSSION
There are several reports in the literature about the
synthesis of 4-keto derivatives of thiazolidine and
thiazinane heterocyclic rings. These rings have been
synthesized from three components namely an amine,
aldehyde, or ketone and a sulfanyl acid (Scheme 1). The
synthesis can be accomplished in two ways. Firstly, it
can be a two-step process in which the first step is the
condensation of aldehyde or ketone with an amine to
yield Schiff’s base. The second step is the condensation
of Schiff’s base with sulfanyl acid. Nucleophilic attack of
sulfur on carbon of the imine group of Schiff’s base
followed with intramolecular cyclization constitutes the
second step of synthesis. Water is being eliminated in the
cyclization step and hence, a few substances such as
molecular sieves, N,N0-dicyclohexylcarbodiimide (DCC),
and ZnCl2, having strong affinity with water, have also
been reported to be employed in the synthesis. Recently,
some workers have resorted to different catalysts such as
HClO4–SiO2 [23], zeolite [24], ionic liquids [25],
CdZr4(PO4)6 [26], and nano-colloidal silica [28]. Most of
the previously reported procedures utilize non-recyclable
catalysts and hazardous chemicals besides obtaining
products in moderate yields. In this endeavor, we have
succeeded to obtain alkanediyl-bis-2-arylthiazolidin-4-
ones and alkanediyl-bis-2-aryl-1,3-thiazinan-4-ones by
utilizing DCC in dioxane at room temperature under
neuropathy,
and
cataract.
Bis-thiazolidin-4-one
derivatives (Fig. 1) have shown COX-1/COX-2 inhibitor
activity [17]. Also, bis(benzofuran-1,3-thiazinan-4-ones)
(Fig. 2) showed potent inhibitory activity against
chikenguniya virus [18]. In continuation to our studies on
various synthesis pathways of thiazolidin-4-one
derivatives [19–22], we report here ultrasound-assisted
efficient synthesis method and subsequent antimicrobial
© 2019 Wiley Periodicals, Inc.

A. Kaur, A. P. Kaur, P. Gautam, D. Gautam, and R. P. Chaudhary
Vol 000
in 48% yield. To optimize the reaction conditions, several
experiments were performed by varying molar ratio of
the reactants, and yield of the product was estimated in
each case. It was found that maximum yield of the
product, that is, 78% was obtained when slight excess of
thioglycolic acid (3.0 mmol) for 1.0 mmol of diamine
and 2.0 mmol of aldehyde was used in the reaction.
Requirement of slight excess of thioglycolic acid than its
molar ratio may probably be because of occurrence of
many side reactions of it with DCC [27].
Figure 1. (bis-thiazinanone as chikengunia inhibitor). [Color figure can
be viewed at wileyonlinelibrary.com]
The reaction, in case of all the substrates reported in
Scheme 2, was completed in 15–20 min time (TLC). In
the workup of the reaction, the ethyl acetate extract was
washed with citric acid for complete removal of DCU.
The rationale of the present studies is that reaction
completes quickly under ultrasonic conditions and the
products are obtained in quantitative yields (75–88%)
except in 3c (68%). The structure of bis-thiazolidin-4-one
(2a) was established by spectral data as follows. IR
spectrum of 2a showed a peak at 1668 cmꢀ1 ascribed to
carbonyl group. A singlet appeared at δ 5.68 ppm in
proton NMR of compound 2a that is attributed to HA
protons. Aromatic protons appeared between δ 7.28 and
7.36 ppm. Appearance of a doublet of doublet at δ
3.8 ppm is attributed to one of the protons of SCH2
group. This is because of the interaction of this proton
with geminal proton and HA proton at C-2. 1H NMR
spectrum displayed double doublet at δ 3.51 ppm, which
is ascribed to second hydrogen of SCH2 group. This is
because of its interaction with one geminal proton and
another diastereotropic proton of N─CH2─CH2─N
group. The ethylene protons of ─N─CH2─CH2─N─
Figure 2. (bis-thiazolidinone as COX inhibitor). [Color figure can be
viewed at wileyonlinelibrary.com]
ultrasonic conditions. This method has benefits of being
rapid, clean, and highly yielding.
A pilot reaction was performed with ethylenediamine
(1.0 mmol), bezaldehyde (2.0 mmol), and thioglycolic
acid (2.0 mmol) in dioxane solvent and DCC (1.5 mmol)
under ultrasonic conditions (n = 0, Scheme 2). The
reaction was completed in about 12 min as the progress
was tracked with thin-layer chromatography (TLC). The
reaction mixture was filtered to separate out dicyclohexyl
urea (DCU) and the filtrate was brought to dryness under
vacuo. The residue was extracted with ethyl acetate and
the extract was washed with citric acid and sodium
bicarbonate solutions for complete removal of DCU.
Workup of extract finally furnished the crystalline solid
Scheme 1. General method of constructing thiazolidin-4-one ring. [Color figure can be viewed at wileyonlinelibrary.com]
Scheme 2. Carobodiimide and ultrasound prompted synthesis of alkanediyl-bis-thiazolidin-4-ones and alkanediyl-bis-thiazinan-4-ones. [Color figure can
be viewed at wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis of Bis-thiazolidin-4-ones and Bis-thiazinan-4-ones
appeared as two quartets of quartets or multiplets between
δ 2.6 and 3.5 ppm owing to the anisotropic effect of ketone
group and phenyl ring. 13C NMR spectrum of compound
2a exhibited carbonyl peaks at δ 168.5 and δ 156.5 ppm.
The carbon attached to the sulfur appeared at δ 61.2 ppm.
A slight excess of carbons in 13C NMR spectrum are
because of formation of mixture of diastereoisomers. The
mass spectral data of 2a showed a peak at m/z 384
(85%), which arise as a result of molecular ion formation.
The spectral data of 2a corroborated by the assigned
structure. Compound 2c (n = 1, R = C6H5, Scheme 2)
was obtained by the reaction of 1,3-diamino propane with
benzaldehyde and thioglycolic acid following the same
procedure. Bis-thiazinan-4-ones 3 were obtained from 1
following the procedure similar to that of compound 2
except using 3-mercaptopropionic acid in place of
thioglycolic acid. The structures of 3 were also spectrally
characterized as follows. A strong peak at 1634 cmꢀ1 in
the IR spectrum of 3a resulted from ketone group of
thiazolidinone ring. A signal at δ 5.89 ppm in proton
NMR of 3a because of HA proton suggests that the
cyclization had occurred. A molecular ion peak at m/z
412 (38%) in mass spectral data of compound 3a
endorses the assigned structure. The structure of
remaining derivatives can similarly be established.
C═O group. Finally, mass analysis of this compound
revealed molecular ion peak at m/z 398 validating the
assigned structure.
BIOLOGICAL ASSAY OF THE SYNTHESIZED
COMPOUNDS
The
synthesized
compounds
alkanediyl-bis-2-
arylthiazolin-4-ones
2
and alkanediyl-bis-2-aryl-1,3-
thiazinan-4-ones 3 (Scheme 2) were assayed against
bacteria and fungi stains by the method reported in our
earlier communication [20]. The minimum inhibitory
concentration (MIC) values in μg/mL have been reported
in Table 1. All the derivatives have exhibited broad range
inhibition of bacteria and fungi. As compared with other
congeners, 2b, 2d, 3b, and 3d have shown reasonable
activity against bacteria. This may probably be attributed
to the p-chloro-substituted aryl group in these derivatives.
Compounds 2b and 3a have demonstrated their inhibition
ability against all the fungi used in the experiment.
CONCLUSION
A facile single step synthetic procedure for alkanediyl-
bis-2-arylthiazolidin-4-ones and alkanediyl-bis-2-aryl-1,3-
thiazinan-4-ones under ultrasonic conditions has been
ensued. Improved yields and clean isolation of products
are some of the benefits of this approach.
The structure of 2c was established by spectral analysis
as well. In 1H NMR spectrum of 2c, a singlet at δ
5.74 ppm was assigned to HA proton. The 13C NMR of
2c showed signal at δ 170.5 ppm corresponding to the
Table 1
Antibacterial and antifungal activities of compounds 2 and 3.
Antimicrobial activity (MIC in μg/mL)
Gram-negative
Fungi
Gram-positive
Staphylococcus
aureus
Pseudomonas
aeruginosa
Aspergillus
niger
Candida
albicans
Aspergillus
fumigates
Entry
Escherichia coli
2a
50
50
25
25
25
25
2b
2c
2d
3a
3b
3c
3d
Cipro
25
25
12.5
25
12.5
25
12.5
6.25
—
6.25
25
12.5
25
25
25
12.5
6.25
—
25
25
12.5
12.5
12.5
25
12.5
12.5
12.5
—
12.5
25
12.5
12.5
50
50
50
—
6.25
12.5
50
25
12.5
50
50
50
—
6.25
12.5
25
12.5
12.5
25
6.25
—
Miconazole
6.25
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Kaur, A. P. Kaur, P. Gautam, D. Gautam, and R. P. Chaudhary
EXPERIMENTAL
Ethanediamine,
Vol 000
White crystalline solid, yield 78%, mp 224–25°C, IR
(ν,cmꢀ1); 1668 (C═O), 1620 (C═C), 1560 (C═C), 1H
NMR (400 MHz, DMSO-d6) δ; 2.65 (dd, 2H, CH2,
J = 5.8 Hz, 8.1 Hz), 3.51 (dd, 2H, CH2, J = 8.1 Hz,
5.3 Hz), 3.61 (d, 2H, CH2, J = 15.5 Hz), 3.80 (dd, 2H,
CH2, J = 13.8 Hz, 1.7 Hz), 5.68 (s, 2H, HA), 7.28–
7.31 (m, 4H, Ph), 7.33–7.36 (m, 6H, Ph); 13C NMR
(100 MHz, DMSO-d6) 168.5 (C═O), 156.5, 139.9,
128.4, 127.7, 126.3, 61.2, 47.4, 44.4, 40.1, 34.0, 33.3,
25.2, 24.4, 21.1; Mass: m/z 384 (85%, M+) 178 (100%,
M+-2PhCN). Anal. Calcd for C20H20N2S2O2: C, 62.5;
H, 5.2; N, 7.29; S, 16.7. Found: C, 62.73; H, 5.45; N,
7.42; S, 16.48%.
Instrumentations.
1,3-
diaminopropane, DCC, thioglycolic acid, and 3-
mercaptopropionic acid were procured form Sigma and
were used as such. The melting points of the obtained
products were checked with open capillaries on a melting
point apparatus and are uncorrected. Proton and carbon
NMR spectra were obtained in deuterated dimethyl
sulfoxide solvent on BRUKER AVANCE II 400 MHz
instrument. Tetramethylsilane was used as an internal
standard and the chemical shifts are expressed in parts per
million (ppm). Perkin Elmer (RZX) FTIR spectrometer
was employed for recording IR spectra and the frequencies
are expressed in cmꢀ1. Euro EA 3000 Elemental Analyzer
was utilized for determination of percentage of different
elements present in the synthesized compounds. Shimadzu
GC–MS QP 2010 Ultra spectrometer was used for
3,30-(Ethane-1,2-diyl)bis(2-(4-chlorophenyl)thiazolidin-4-
one) (2b).
molecular
mass
determinations.
Ultrasonication
experiments were performed on Cole Parmar CPX500,
20 KHz, and 500 Watt ultrasonicator.
General procedure for synthesis of 2. Thioglycolic acid
(3.0 mmol) was added to the stirred solution of ethylene
diamine (1.0 mmol) and aryl aldehyde (2.0 mmol) in
10 mL of dioxane. The stirring was continued for 5 min.
DCC (1.2 mmol) was then added to the reaction mixture.
The reaction mixture was then kept under ultrasonication
for 15–20 min. The reaction progress was tracked by TLC.
After the completion of the reaction, the mixture was
filtered to separate out dicyclohexy urea, generated from
reaction of DCC with water. The filtrate was subjected to
vacuum distillation under reduced pressure to remove
dioxane. The residue thus obtained was extracted with
ethyl acetate. To remove unreacted thioglycolic acid and
traces of DCU, the extract was then washed with 5%
aqueous solutions of sodium bicarbonate and citric acid,
respectively. Brine solution was used for final washing to
the extract. After drying with anhydrous sodium sulfate,
the extract was reduced to one fourth of its volume in
vacuo. The separated solid was then recrystallized from
ethanol.
White fluffy solid, yield 76%, mp 254–55°C, IR (ν,
1
cmꢀ1); 1665 (C═O), 1618 (C═C), H NMR (400 MHz,
DMSO-d6) δ; 2.72 (dd, 2H, CH2, J = 5.7 Hz, 8.2 Hz),
3.62 (dd, 2H, CH2, J = 8.3 Hz, 5.4 Hz), 3.68 (d, 2H,
CH2, J = 15.6 Hz), 3.84 (dd, 2H, CH2, J = 14.2 Hz,
1.5 Hz), 5.72 (s, 2H, HA), 7.35 (d, 4H, Ar─H,
J = 7.5 Hz), 7.42 (d, 4H, Ar─H, J = 8.2 Hz); 13C
NMR (100 MHz, DMSO-d6) 170.2 (C═O), 155.6,
138.7, 129.3, 126.7, 126.5, 62.3, 48.3, 43.2, 39.2, 36.1,
26.2, 25, 23.2; Mass: m/z 452 (76%, M+) 454 (19%,
M++2). Anal. Calcd for C20H18Cl2N2O2S2: C, 52.98; H,
4.00; N, 6.18; S, 14.14. Found: C, 53.12; H, 4.08; N,
6.38; S, 14.29%.
3,30-(Propane-1,3-diyl)bis(2-phenylthiazolidin-4-one)
(2c).
“3,30-(Ethane-1,2-diyl)bis(2-phenylthiazolidin-4-one)”
(2a).
This compound was also obtained by different
method and previously reported [28], but we have
reported its mass spectral data first time.
White solid, yield 75%, mp 105–108°C, IR (ν,cmꢀ1
)
1
1670 (C═O); H NMR (400 MHz, DMSO-d6) δ; 1.46–
1.49 (m, 2H, CH2), 2.43–2.51 (m, 2H, CH2), 3.34–3.41
(m, 2H, CH2), 3.57 (d, 2H, CH2, J = 15.4 Hz), 3.82
(d, 2H, CH2, J = 17 Hz), 5.74 (s, 2H, HA), 7.34–7.43
(m, 10H, C6H5). 13C NMR (100 MHz, DMSO-d6)
178.5 (C═O), 139.8, 128.8, 128.8, 127.0, 61.6, 31.9,
23.5; Mass: m/z 398 (98%, M+); Anal. Calcd for
C21H22N2O2S2: C, 63.31; H, 5.52; N, 7.03; S, 16.08.
Found C, 63.65; H, 5.19; N, 7.24; S, 15.78%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis of Bis-thiazolidin-4-ones and Bis-thiazinan-4-ones
3,30-(Propane-1,3-diyl)bis(2-(4-chlorophenyl)thiazolidin-4-
one) (2d).
32.5, 23.6; Mass: m/z 412 (38%, M+), 290 (96%, M-
2SCH2CH3). Anal. Calcd for C22H24N2S2O2: C, 64.07;
H, 5.82; N, 6.8; S, 15.53. Found: C, 64.46; H, 5.65; N,
6.37; S, 15.27%.
3,30-(Ethane-1,2-diyl)bis(2-(4-chlorophenyl)-1,3-thiazinan-
4-one) (3b).
White crystalline solid, yield 78%, mp 210–12°C, IR (ν,
1
cmꢀ1) 1676 (C═O); H NMR (400 MHz, DMSO-d6) δ;
1.52–1.58 (m, 2H, CH2), 2.67–2.74 (m, 2H, CH2), 3.47–
3.56 (m, 2H, CH2), 3.74 (d, 2H, CH2, J = 15.4 Hz), 3.88
(d, 2H, CH2, J = 17 Hz), 5.82 (s, 2H, HA), 7.67 (d, 4H,
ArH, J = 7.6 Hz), 7.75 (d, 4H, Ar, J = 7.8 Hz). 13C
NMR (100 MHz, DMSO-d6) 181.2 (C═O), 140.6, 132.8,
129.1, 128.2, 62, 36.2, 31.6, 24.2; Mass: m/z 466 (48%,
White fluffy solid, yield 83%, mp 202–204°C, IR (ν,
1
cmꢀ1); 1638 (C═O), H NMR (400 MHz, DMSO-d6) δ;
1.56–1.62 (m, 2H, CH2,), 1.64–1.72 (m, 2H, CH2), 1.76–
1.8 (m, 2H, CH2), 2.65–2.76 (m, 2H, CH2), 4.23 (dd, 2H,
SCH2, J = 6.2 Hz, 7.8 Hz), 5.72 (d, 2H, CH2,
J = 7.7 Hz), 5.9 (s, 2H, HA), 7.36 (d, 4H, Ph,
J = 7.5 Hz) 7.48 (d, 4H, Ph, J = 8.0 Hz); 13C NMR
(100 MHz, DMSO-d6) 162 (C═O), 145.6, 137.4, 131.6,
129.3, 61.8, 35.26, 32.3, 23.4; Mass: m/z 480 (32%, M+),
484 (9.6%, M++4). Anal. Calcd for C22H22Cl2N2O2S2: C,
54.88; H, 4.61; N, 5.82; S, 13.32. Found: C, 54.97; H,
4.75; N, 5.98; S, 13.52%.
M+), 468 (14%,
M
+
2); Anal. Calcd for
C21H20Cl2N2O2S2: C, 53.96; H, 4.31; 15. N, 5.99; S,
13.72. Found: C, 54.11; H, 4.46; 15. N, 6.17; S, 13.85%.
General procedure for the synthesis of 3.
3-
Mercaptopropionic acid (3.0 mmol) was added to the
stirred solution of diaminoalkane (1.0 mmol) and aryl
aldehyde (2.0 mmol) in 10 mL of dioxane. The stirring
was continued for 5 min. DCC (1.2 mmol) was then
added to the reaction mixture. The reaction mixture was
then kept under ultrasonication for 15–20 min. The
reaction progress was tracked by TLC. After the
completion of the reaction, the mixture was filtered to
separate out DCU, generated from reaction of DCC with
water. The filtrate was subjected to vacuum distillation
under reduced pressure to remove dioxane. The residue
thus obtained was extracted with ethyl acetate. To
remove unreacted thioglycolic acid and traces of DCU,
the extract was then washed with 5% aqueous solutions
of sodium bicarbonate and citric acid, respectively. Brine
solution was used for final washing to the extract. After
drying with anhydrous sodium sulfate, the extract was
reduced to one fourth of its volume in vacuo. The
separated solid was then recrystallized from ethanol.
3,30-(Propane-1,3-diyl)bis(2-pheny-1,3-thiazinan-4-one)
(3c).
White crystals, yield 68%, mp 155–157°C, IR (ν,cmꢀ1);
1640 (C═O), 1H NMR (400 MHz, DMSO-d6) δ; 1.52–1.58
(m, 2H, CH2), 2.67–2.74 (m, 2H, CH2), 3.47–3.56 (m, 2H,
CH2), 3.74 (d, 2H, CH2, J = 15.4 Hz), 3.88 (d, 2H, CH2,
J = 17 Hz), 4.23 (m, 2H, CH2), 5.72 (d, 2H, CH2,
J = 7.7 Hz), 5.78 (s, 2H, HA), 7.36 (m, 5H) 7.44 (m, 5H,
Ph); 13C NMR (100 MHz, DMSO-d6) 163.6 (C═O),
144.3, 134.2, 128.5, 126.3, 59.9, 38.4, 34.1, 23.5; Mass:
m/z 426 (16%, M+). Anal. Calcd for C23H26N2O2S2: C,
64.78; H, 6.10; N, 6.57; S, 15.02. Found: C, 64.46; H,
6.33; N, 6.82; S, 15.28%.
3,30-(Ethane-1,2-diyl)bis(2-pheny-1,3-thiazinan-4-one)
(3a).
3,30-(Propane-1,3-diyl)bis(2-(4-chlorophenyl)-1,3-
thiazinan-4-one) (3d).
White crystalline solid, yield 88%, mp 211–215°C, IR
1
(ν,cmꢀ1); 1634 (C═O), H NMR (400 MHz, DMSO-d6)
δ; 1.48–1.52 (m, 2H, CH2,), 1.59–1.64 (m, 2H, CH2),
1.70–1.74 (m, 2H, CH2), 2.60–2.72 (m, 2H, CH2), 4.15
(dd, 2H, SCH2, J = 5.8 Hz, 7.7 Hz), 5.63 (d, 2H, CH2,
J = 7.8 Hz), 5.89 (s, 2H, HA), 7.21 (d, 4H, Ph,
J = 7.2 Hz) 7.32 (t, 2H, Ph, J = 5.3 Hz) 7.40 (t, 4H, Ph,
J = 7.7 Hz); 13C NMR (100 MHz, DMSO-d6) 165.5
(C═O), 145.8, 136.6, 132.1, 129.2, 128.6, 62.9, 37.3,
White crystalline solid, yield 64%, mp 218–220°C, IR
1
(ν,cmꢀ1); 1636 (C═O), H NMR (400 MHz, DMSO-d6)
δ; 1.5–1.56 (m, 2H, CH2), 2.71–2.75 (m, 2H, CH2), 3.5–
3.58 (m, 2H, CH2), 3.81 (d, 2H, CH2, J = 15.2 Hz), 3.9
(d, 2H, CH2, J = 16.8 Hz), 4.27 (m, 2H, CH2), 5.75 (d,
2H, CH2, J = 7.8 Hz), 5.8 (s, 2H, HA), 7.41 (d, 4H, Ar,
J = 7.6 Hz), 7.52 (d, 4H, Ar, J = 7.2 Hz); 13C NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Kaur, A. P. Kaur, P. Gautam, D. Gautam, and R. P. Chaudhary
Vol 000
[13] Yakub, A.; Mohammad, S. A.; Hinna, H.; Asif, H.; Abhijeet,
D.; Sameena, B.; Chetna, K. Bioorg Med Chem Lett 2017 27, 1017.
[14] Alice, K.; Patrícia, D. N.; Adriana, M. d. N.; Claudio, M. P. P.;
Gabriela, H. M.; Patrícia, S. N.; Maureen, H. V. F.; Silvia, O. H.; Wilson,
C. Eur J Med Chem 2013, 64, 74.
[15] Xue-ing, S.; Ya-Hong, L.; Jia, S.; Zhen-Lei, Z.; Cheng-Zhi, X.;
Xin, Q.; Wei-Guo, B.; Jing-Yuan, X. Eur J Med Chem 2018, 157, 188.
[16] Sambhaji, T. D.; Amarsinh, R. D.; Lalit, D. K.; Manisha, A. D.
S.; Ramrao, A. M. J Heterocyclic Chem 2017, 54, 125.
[17] Vigorita, M. G.; Ottana, R.; Monforte, F.; Maccari, R.;
Trovato, A.; Monforte, M. T.; Taviano, M. F. Bioorg Med Chem Lett
2001, 11, 2791.
[18] Hwu, J. R.; Gupta, N. K.; Tsay, S. C.; Huang, W. C.;
Albulescu, I. C.; Kovacikova, K.; Van Hemert, M. J. Antiviral Res
2017, 146, 96.
[19] Gautam, D.; Chaudhary, R. P. J Mol Struct 2018, 1080, 137.
[20] Gautam, D.; Chaudhary, R. P. Spectrochim Acta Part A 2015,
135, 219.
[21] Gupta, R.; Chaudhary, R. P. J Sulfur Chem 2014, 35, 86.
[22] Poonam, G.; Deepika, G.; Chaudhary, R. P. J Mol Struct 2018,
1160, 333.
[23] Kumar, D.; Sonawane, M.; Pujala, B.; Jain, V. K.; Bhagat, S.;
Chakraborti, A. K. Green Chem 2013, 15, 2872.
[24] Meshram, J.; Ali, P.; Tiwari, V. Green Chem Lett Rev 2010, 3,
195.
[25] Mobinikhaledi, A.; Amiri, A. K. Lett Org Chem 2013, 10,
764.
[26] Javad, S. G.; Seyed, H. N.; Hossein, S. A. J Sulfur Chem 2017,
38, 195.
(100 MHz, DMSO-d6) 161.4 (C═O), 146.3, 138.7, 132.4,
127.6, 63.6, 38.4, 33.5, 28.7; Mass: m/z 494 (18%, M+),
496 (5%, M + 2). Anal. Calcd for C23H24Cl2N2O2S2: C,
55.75; H, 4.88; N, 5.65; S, 12.94. Found: C, 55.87; H,
5.03; N, 5.82; S, 13.24%.
REFERENCES AND NOTES
[1] Willson, T. M.; Cobb, J. E.; Cowan, D. J.; Wiethe, R. W.;
Correa, I. D.; Prakash, S. R.; Beck, K. D.; Moore, L. B.; Kliewer, S. A.;
Lehmann, J. M. J Med Chem 1996, 39, 665.
[2] Kaminsky, D. V.; Kryshchyshyn, A. P.; Lesyk, R. B. J Org
Pharm Chem 2013, 11, 26.
[3] Maria, F.; Panagiotis, Z.; Charalampos, C.; Anthi, P.; Phaedra,
E.; Christophe, T.; Micheline, H.; Athina, G.; Ana, C.; Marina, S. Bioorg
Med Chem 2018 26, 4664.
[4] Anna, P. G. N.; Arfat, N. S.; Sameer, I. S.; Firoz, A. K. K.;
Jaiprakash, N. S.; Devanand, B. S. Bioorg Med Chem Lett 2014, 24,
5558.
[5] Rahul, S.; Sushama, J.; Nandini, M.; Dipen, D.; Devidas, C.;
Archana, S.; SusanIdicula, T.; Vanangamudi, M.; Seturam, B. K.;
Srikanth, T.; Ramesh, P.; Smita, K. Bioorg Chem 2017, 71, 211.
[6] Amin, K. M.; Kamel, M. M.; Anwar, M. M.; Khedr, M.; Syam,
Y. M. Eur J Med Chem 2010, 45, 2117.
[7] Fazal, R.; Khalid, Z.; Hayat, U.; Muhammad, T.; Abdul, W.;
Muhammad, T. J.; Wajid, R.; Muhammad, A.; Reaz, U.; Imad, U.;
Humna, A.; Aftab, A. K.; Khalid, M. K. Bioorg Chem 2015, 63, 123.
[8] Christoph, N.; Verena, N. S.; Mira, A. M.; Behnam, A. K.;
Ralf, B.; Christian, D. K. J Med Chem 2013, 56, 8389.
[9] Dmytro, H.; Borys, Z.; Olexandr, K.; Philippe, G.; Roman, L.
Eur J Med Chem 2014, 85, 245.
[10] Maria, F.; Panagiotis, Z.; Charalampos, C.; Anthi, P.; Phaedra,
E.; Christophe, T.; Micheline, H.; Athina, G.; Ana, C.; Marina, S. Bioorg
Med Chem 2018, 26, 4664.
[11] Mohammad, F. A.; Danish, I.; Md, I. H.; Kamal, A.; Fernando,
A.; Amir, A. Eur J Med Chem 2018, 144, 544.
[27] Lataifeh, A.; Kraatz, H. B. Inorg Chim Acta 2009, 362, 3867.
[28] Safari-Ghomi, J.; Nazemzadeh, S. H.; Shabazi-Alavi, H. Z.
Naturforsh , 72, 927.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
[12] Gina, N. T.; Salwa, M. F.; Hayam, M. A.; Mounir, A. K.;
Rasha, A. N.; Ibrahim, M. L. Bioorg Chem 2018, 80, 164.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet