One-pot sonochemical synthesis of 1,3-thiazolidin-4-ones using nano-CdZr4(PO4)6 as a robust heterogeneous catalyst

Article abstract of DOI:10.1016/j.ultsonch.2015.12.008

An efficient three-component synthesis of 1,3-thiazolidin-4-ones is described by one-pot condensation of aldehydes, aniline and thioglycolic acid with nano-CdZr₄(PO₄)₆ as a robust heterogeneous catalyst under ultrasonic ir

Full text of DOI:10.1016/j.ultsonch.2015.12.008

Accepted Manuscript
One-pot sonochemical synthesis of 1,3-thiazolidin-4-ones using nano-
CdZr4(PO4)6 as a robust heterogeneous catalyst
Javad Safaei-Ghomi, Maryam Navvab, Hossein Shahbazi-Alavi
PII:
S1350-4177(15)30101-2
DOI:
http://dx.doi.org/10.1016/j.ultsonch.2015.12.008
ULTSON 3064
Reference:
Ultrasonics Sonochemistry
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11 December 2015
Please cite this article as: J. Safaei-Ghomi, M. Navvab, H. Shahbazi-Alavi, One-pot sonochemical synthesis of 1,3-
thiazolidin-4-ones using nano-CdZr4(PO4)6 as a robust heterogeneous catalyst, Ultrasonics Sonochemistry (2015),
doi: http://dx.doi.org/10.1016/j.ultsonch.2015.12.008
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One-pot sonochemical synthesis of 1,3-thiazolidin-4-ones using
nano-CdZr4(PO4)6 as a robust heterogeneous catalyst
Javad Safaei-Ghomi*, Maryam Navvab, Hossein Shahbazi-Alavi
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 51167,
I. R. Iran
Corresponding Author Tel.: +98 31 55912385; fax: +98 31 55552935; *E-mail:
safaei@kashanu.ac.ir
Abstract
An efficient three-component synthesis of 1,3-thiazolidin-4-ones is described by one-pot
condensation of aldehydes, aniline and thioglycolic acid with nano-CdZr4(PO4)6 as a robust
heterogeneous catalyst under ultrasonic irradiation. Use of simple and readily available starting
materials, experimental simplicity, applying the sonochemical methodology as an efficient
method and innocuous means of activation in synthetic chemistry are some advantages of this
protocol.
Keywords: CdZr4(PO4)6, 1,3-Thiazolidin-4-ones, Ultrasonic irradiation, Heterogeneous catalysts, Three-
component condensation
1

1. Introduction
Thiazolidinones are valuable synthetic scaffolds for both medicinal and synthetic organic
chemists. Thiazolidinones exhibit various pharmacological activities such as anti-HIV [1-5],
antimicrobials [6,7], antihistaminic [8,9], anti-YFV (Yellow fever virus) [10], anti-cancer [11],
antiinflammatory [12] and antioxidant [13]. Therefore, the development of simple and efficient
synthetic protocols for the construction of more elaborate and usefully functionalized
thiazolidinones are still desirable. Undoubtedly, the synthesis of thiazolidinones through
multicomponent reactions (MCR) has been paid much attention due to excellent synthetic
efficiency, inherent atom economy, the use of readily available starting materials, experimental
simplicity and environmental friendliness [14-16]. The possibility of accomplishing
multicomponent reactions with a heterogeneous catalyst under ultrasonic irradiation could
improve their effectiveness from cost-effectiveness and environmental points of view. The
ultrasound approach offers several advantages, including enhanced organic reaction rates,
formation of purer products in high yields, simple experimental conditions, and waste
minimization compared with traditional methods [17-19]. Ultrasound irradiation has been
utilized to accelerate the chemical reactions proceed through the formation, growth, and
implosive collapse of bubbles in a liquid. Cavitation serves as a means of concentrating the
dispread energy of sound [20-21]. Recently, ultrasound irradiation was applied for the
appropriate and rapid synthesis of 2-aryl-3-(piperonylmethyl)-1,3-thiazolidin-4-ones from
piperonilamine [22], synthesis of new 2-imino-1,3-thiazolidin-4-ones [23] and synthesis of
thiazolidinones from 2-aminopyridineand 2-picolilamine [24]. Nanocatalysts have been emerged
as an alternative approach for the development of many significant organic reactions under
ultrasonic irradiations [25-26]. Nanocatalysts are isolated and recovered through filtration or
2

centrifugation methods, and are acknowledged to possess a wide range of specific features
including high activity, great selectivity, high stability, efficient recovery and good recyclability.
MZr4(PO4)6 structure ceramics have been interested because of their unique properties and
potential applications in diverse fields [27-28]. According to the above results we used nano-
CdZr4(PO4)6 for the synthesis of 1,3-thiazolidin-4-ones. Recently, the synthesis of 1,3-
thiazolidin-4-ones has been reported using MCRs in the presence of diverse catalysts including
HClO4-SiO2 [29], Ionic liquid immobilized on FeNi3 [30], Fe3O4/SiO2/Salen/Mn/IL MNPs [31],
Bi(SCH2COOH)3 [32], and Saccharomyces cerevisiae [33]. Many methods for the synthesis of
1,3-thiazolidin-4-ones are known, but some of these methods have certain drawbacks, including
long reaction times, use of toxic and non-reusable catalyst and utilize of specific conditions.
In the current work, we disclosed a novel methodology for the synthesis of 1,3-thiazolidin-4-
ones by one-pot condensation of aldehydes, aniline and thioglycolic acid with nano-CdZr4(PO4)6
as a robust heterogeneous catalyst under ultrasonic irradiation.
Scheme 1.
2. Experimental
2.1. Materials and Apparatus
All organic materials were purchased commercially from Sigma–Aldrich and Merck and
were used without further purification. A multiwave ultrasonic generator (Sonicator 3200;
Bandelin, MS 73, Germany), equipped with a converter/transducer and titanium oscillator (horn),
12.5 mm in diameter, operating at 20 kHz with a maximum power output of 200 W, was used
for the ultrasonic irradiation. The ultrasonic generator automatically adjusted the power level. All
melting points are uncorrected and were determined in capillary tube on Boetius melting point
3

microscope. FT-IR spectra were recorded with KBr pellets using a Magna-IR, spectrometer 550
Nicolet. NMR spectra were recorded on a Bruker 400 MHz spectrometer with DMSO-d6 as
solvent and TMS as internal standard. CHN compositions were measured by Carlo ERBA Model
EA 1108 analyzer. Powder X-ray diffraction (XRD) was carried out on a Philips diffractometer
of X’pert Company with monochromatized Zr Kα radiation (λ= 1.5406 Å). In order to
investigate the particle size and morphology of the synthesis structures nano-CdZr4(PO4)6, FE-
SEM images of the products visualized by a HITACHI S4160 Field Emission Scanning Electron
Microscope.
2.2. Preparation of nano-CdZr4(PO4)6
ZrOCl2was used as zirconium source. Firstly 1 mmol (322 mg) of ZrOCl2.8H2O and 1 mmol
(266 mg) of Cd(OAc)2·2H2O were added in 15 mL of HO(CH2)2OH and sonicated at 30 W
power to completely dissolution. Afterward 0.8 ml H3PO4 (85%), 4 mmol of NH4Cl and 1.4 mL
of CH3NH2 water solution (25.0-30.0%) were added consecutively and sonicated for 30 min.
Then, the reaction mixture was transferred into a Teflon-lined autoclave under autogenous
o
pressure at 200 C for 5 days. When the reaction was completed, dispersed precipitate was
obtained. The solid was filtered and washed with distilled water and ethanol several times.
o
o
Subsequently product was dried at 50 C for 5 h and calcined at 700 C for 2 h. Afterward the
solid was added in 20 mL of DMF and sonicatedat 95 W power for 2 h. Finally the resulting
product was filtered, washed with distilled water and absolute ethanol and dried at 150 oC for 2 h
in vacuum to afford pure nano-CdZr4(PO4)6 ceramics.
2.3. General procedure for the preparation of 1,3-thiazolidin-4-ones
A mixture of aldehydes (2 mmol), aromatic amine (2 mmol), thioglycolic acid (2 mmol) and
0.50 mol% (12 mg) of nano-CdZr4(PO4)6 in PhMe (15 mL) was sonicated at 60 W power. The
4

reaction was monitored by TLC. After completed reaction, hot CH3OH was added to dilute the
reaction mixture after terminating the reaction. The reaction mixture was filtered until
heterogeneous catalyst was recovered. The filtrate was evaporated and recrystallized with n-
hexane/ethyl acetateto get pure product.
2.4. Representative spectral data
2-(2-chlorophenyl)-3-phenylthiazolidin-4-one (4a) :
White solid, m.p 120-124 ºC, IR (KBr) cm-1: 1683, 1598, 1521, 1455, 732; 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 3.89 (d, 1H, 2J= 15.6 Hz), 3.96 (d, 1 H, 2J= 15.6 Hz), 6.76 (s, 1H), 7.12 (m,
1H, J = 7.2 Hz), 7.16-7.45 (m, 4 H), 7.47-7.54 (m, 3 H), 7.61 (d, 1H, J = 7.00 Hz); 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 33.20, 60.02, 124.50, 125.20, 126.53, 128.02, 129.10, 129.60,
135.12, 135.72, 137.25, 146.83, 171.10; Anal. calcd for C15H12ClNOS: C, 62.17; H, 4.17; N,
4.83; S, 11.07;Found: C, 62.10; H, 4.09; N, 4.71; S, 10.89.
2-(2-Nitrophenyl)-3-phenylthiazolidin-4-one (4b):
Cream Solid; m.p112-114ºC, IR (KBr) cm-1: 1686, 1595, 1521, 1449, 1343; 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 3.84 (d, 1H, 2J= 16 Hz), 3.97 (d, 1H,2J= 16 Hz), 6.78 (s, 1H), 7.12 (m, 1H, J
= 7.2 Hz), 7.16-7.27 (m, 4H), 7.47-7.49 (t, 1H, J = 8Hz), 7.53 - 7.70 (m, 2H), 7.98-8.00 (d, 1H, J
= 8 Hz); 13C NMR (100 MHz, DMSO-d6): δ (ppm) 32.29, 59.74, 125.53, 127.04, 127.10, 128.05,
129.36, 129.98, 135.02, 135.89, 137.73, 147.40, 171.36; Anal. calcd for C15H12N2O3S: C, 59.99;
H, 4.03; N, 9.33; S, 10.68; Found: C, 59.88; H, 3.95; N, 9.42; S, 10.57.
5

3-phenyl-2-(pyridin-2-yl)thiazolidin-4-one (4c):
White solid; m.p150-152ºC, IR (KBr) cm-1: 1673, 1587, 1524, 1497, 1432; 1H NMR (400 MHz,
2
2
DMSO-d6): δ (ppm) 3.80 (d, 1H, J= 15.6 Hz), 4.03 (d, 1H, J= 15.6 Hz), 6.47 (s, 1H), 7.04 (d,
J= 7.2 Hz, 1H), 7.15-7.40 (m, 5H), 7.52 (m, 1H), 7.72 - 7.74 (d, J = 7.4 Hz, 1H), 8.49 (d, J =
13
7.00 Hz, 1H); C NMR (100 MHz, DMSO-d6): δ (ppm) 33.15, 60.21, 124.69, 127.04, 128.02,
129.30, 130.25, 135.05, 135.93, 147.40, 157.30, 171.36; Anal. calcd for C14H12N2OS: C, 65.60;
H, 4.72; N, 10.93; S, 12.51;Found:C, 65.55; H, 4.62; N, 10.99; S, 12.43.
2-(3-Nitrophenyl)-3-phenylthiazolidin-4-one (4d):
Cream solid; m.p179-181ºC, IR (KBr) cm-1: 1676, 1596, 1529, 1521, 1497, 1386, 1348; 1H NMR
2
2
(400 MHz, DMSO-d6): δ (ppm) 3.89(d, 1H, J= 15 Hz), 4.08 (d, 1H, J= 15 Hz), 6.72 (s, 1H),
7.11 (m, 1H, J= 7.2 Hz), 7.19-7.29 (m, 4H), 7.41-7.52 (t, 1H, J= 8 Hz), 7.51-7.72 (d, J= 7.2 Hz,
1H), 7.80 (d, J= 7.2 Hz, 1H),7.98-8.00 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ (ppm) 33.09,
60.14, 125.62, 127.22, 127.26, 128.15, 129.33, 129.93, 135.15, 135.93, 137.82, 147.42, 171.35;
Anal. calcd forC15H12N2O3S:C, 59.99; H, 4.03; N, 9.33; S, 10.68; Found: C, 59.82; H, 3.93; N,
9.40; S, 10.52.
3-phenyl-2-(pyridin-3-yl)thiazolidin-4-one (4e):
1
White solid; m.p135-137ºC, IR (KBr) cm-1: 1673, 1582, 1495, 1431; H NMR (400 MHz,
2
2
DMSO-d6): δ (ppm) 3.88 (d, 1H, J= 15.6 Hz), 4.05 (d, 1H, J= 15.6 Hz), 6.57 (s, 1H), 7.13 (d,
1H, J = 6.4 Hz), 7.29-7.60 (m, 5H), 7.83-7.85 (d, J= 8 Hz, 1H), 7.38-7.40 (d, J=4 Hz, 1H), 8.53
(s, 1H); 13C NMR (100 MHz, DMSO-d6): δ (ppm) 33.19, 60.28, 124.72, 127.05, 128.09, 129.35,
130.29, 135.14, 135.91, 147.47, 157.33, 171.35; Anal. calcd for C14H12N2OS: C, 65.60; H, 4.72;
N, 10.93; S, 12.51; Found:C, 65.51; H, 4.65; N, 10.98; S, 12.40.
6

2-(4-chlorophenyl)-3-phenylthiazolidin-4-one (4f) :
White solid, m.p125-127 º C, IR (KBr) cm-1: 1675, 1595, 1520, 1453, 730; 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 3.94 (d, 1 H, 2J= 15 Hz), 4.02 (d, 1H, 2J= 15Hz), 6.58 (s, 1H), 7.04-7.45 (m,
13
7 H), 7.60-7.68 (m, 2 H); C NMR (100 MHz, DMSO-d6): δ (ppm) 33.10, 59.95, 124.45,
125.22, 126.64, 129.12, 129.60, 135.10, 137.23, 146.81, 171.08; Anal. calcd for C15H12ClNOS:
C, 62.17; H, 4.17; N, 4.83; S, 11.07; Found: C, 62.09; H, 4.05; N, 4.70; S, 10.87.
2-(4-Nitrophenyl)-3-phenylthiazolidin-4-one(4g):
Yellow Solid; m.p133-134ºC, IR (KBr) cm-1: 1686, 1598, 1521, 1521, 1455, 1346; 1H NMR (400
MHz, DMSO-d6): δ (ppm) 3.89 (d, 1 H, 2J= 15 Hz), 4.09 (d, 1 H, 2J= 15 Hz), 6.69 (s, 1H), 7.12-
7.15 (t, 1H, J = 7.2 Hz), 7.27-7.35 (m, 4H), 7.66-7.68 (d, 2 H, J= 8 Hz), 8.10-8.12 (d, 2 H, J= 8
Hz); 13C NMR (100 MHz, DMSO-d6): δ (ppm) 33.11, 60.18, 125.65, 127.26, 128.15, 129.33,
129.93, 135.93, 137.82, 147.42, 171.35; Anal. calcd for C15H12N2O3S: C, 59.99; H, 4.03; N,
9.33; S, 10.68; Found:C, 59.86; H, 3.94; N, 9.41; S, 10.55.
3-phenyl-2-(thiophen-2-yl)thiazolidin-4-one(4h):
White Solid; m.p130-131 ºC, IR (KBr) cm-1: 1686, 1598, 1521, 1521, 1455, 1346;1H NMR (400
2
2
MHz, DMSO-d6): δ (ppm) 3.86 (d, 1 H, J= 15.6 Hz), 3.98 (d, 1 H, J= 15.6 Hz), 6.82 (s, 1H),
13
7.12-7.55 (m, 8 H); C NMR (100 MHz, DMSO-d6): δ (ppm) 33.55, 59.27, 123.64, 125.52,
127.26, 128.15, 129.33, 129.93, 130.99, 139.42, 171.35; Anal. calcd forC13H11NOS2: C, 59.74;
H, 4.24; N, 5.36; S, 24.54; Found:C, 59.65; H, 4.31; N, 5.40; S, 24.60.
7

2-(4-isopropyl-phenyl)-3-phenylthiazolidin-4-one(4i):
1
White Solid; m.p 133-135 º C, IR (KBr) cm-1: 1685, 1595, 1521, 1496, 1455, 1346; H NMR
2
(400 MHz, DMSO-d6): δ (ppm) 1.07 (2 CH3, 6H), 2.60 (1H, CH), 3.81 (d, 1 H, J= 15 Hz), 4.03
2
(d, 1 H, J= 15 Hz), 6.49 (s, 1H), 7.12-7.15 (t, 1 H, J = 7.2 Hz), 7.20-7.25 (m, 4H), 7.42-7.44
13
(d, 2 H, J = 8 Hz), 7.45-7.46 (d, 2 H, J = 8 Hz); C NMR (100 MHz, DMSO-d6): δ (ppm)
22.54, 33.16, 35.50, 60.19, 126.65, 127.29, 127.95, 129.24, 129.62, 135.90, 137.80, 147.30,
171.22 Anal. calcd for C18H19NOS: C, 72.69; H, 6.44; N, 4.71; S, 10.78; Found: C, 72.75; H,
6.49; N, 4.55; S, 10.69.
2,3-diphenylthiazolidin-4-one (4j):
White Solid; m.p 132-134 ºC, IR (KBr) cm-1: 1672, 1594, 1521, 1521, 1455, 1346; 1H NMR (400
2
2
MHz, DMSO-d6): δ (ppm) 3.89 (d, 1 H, J= 15 Hz), 4.09 (d, 1 H, J= 15 Hz), 6.50 (s, 1H), 7.25
(t, 1 H, J= 7.2 Hz), 7.27-7.34 (m, 9H); 13C NMR (100 MHz, DMSO-d6): δ (ppm) 33.08, 59.78,
124.62, 126.24, 128.12, 128.90, 129.92, 135.91, 136.92, 147.25, 171.52; Anal. calcd for
C15H13NOS: C, 70.56; H, 5.13; N, 5.49; S, 12.56; Found: C, 70.48; H, 5.02; N, 5.38; S, 12.49.
3- Results and discussion
3.1. Structural analysis of nano-CdZr4(PO4)6
ZrOCl2 and Cd(OAc)2·2H2O were used as the starting materials for the synthesis of nano-
CdZr4(PO4)6. In this method, the ultrasonic irradiation was performed before and after
solvothermal route. Sonication was used to speed dissolution, by breaking the interactions
between particles. When the solution containing precursor is exposed via an ultrasound
solvothermal route, extremely high pressures and temperatures are produced to generate
CdZr4(PO4)6 nuclei. At the beginning of the reaction, the reactant particles and the molecules of
8

methylamine disperse randomly in the glycol solution under ultrasounic irradiation. The
CdZr4(PO4)6 form gradually around the methylamine molecules. During calcination at a high
temperature, methylamine decomposed into carbon dioxide, carbon monoxide and nitrogen
oxide, thus the nano-CdZr4(PO4)6 were finally obtained. The particle size diameter (D) of the
nano-CdZr4(PO4)6 has been calculated by the Debye–Scherrer equation (D =Kλ/β cos θ), where
β FWHM (full-width at half-maximum or half-width) is in radian and θ is the position of the
maximum of the diffraction peak. K is the so-called shape factor, which usually takes a value of
about 0.9, and λ is the X-ray wavelength. Fig.1 shows the XRD spectra of nano-CdZr4(PO4)6.
According to the Debye–Scherrer equation, the average particle sizes of the as-synthesized nano-
CdZr4(PO4)6 were calculated and the results show that nano-CdZr4(PO4)6 was obtained with an
average diameter of 19-23 nm as confirmed by XRD analysis. In order to investigate the
morphology and particle size of nano-CdZr4(PO4)6, FE-SEM image of nano-CdZr4(PO4)6 was
presented in Fig.2. The FE-SEM image shows particles with diameters in the range of
nanometers.
Fig. 1.
Fig. 2.
3.2. Catalytic behaviors of nano-CdZr4(PO4)6 for the synthesis 1,3-thiazolidin-4-ones
Initially, we focused on systematic evaluation of different catalysts for the model reaction of 4-
chlorobenzaldehyde (2 mmol), aniline (2 mmol) and thioglycolic acid (2 mmol) in different
solvents. We employed various conditions and found that the reaction gave satisfying result in
the presence of nano-CdZr4(PO4)6 under ultrasonic irradiation in toluene (Table 1). The reaction
was carried out with different amounts of nano-CdZr4(PO4)6 as catalyst. As show in Table1, 0.50
9

mol % of nano-CdZr4(PO4)6 as catalyst was suitable and when the amount of catalyst was
increased to 0.70 mol %, but the yield was not improved. The model reaction was carried out in
the presence of various catalysts such as H2SO4, nano-SnO, nano-ZrO2, and nano-CdZr4(PO4)6.
When the reaction was carried out using nano-CdZr4(PO4)6 as the catalyst under ultrasonic
irradiation, the product could be obtained in good yield.
Table 1
In continuation of this method, the role of ultrasonic irradiation and the effect of various powers
of ultrasonic irradiation on the reaction were investigated. The results illustrated that the
sonication certainly affected the reaction system. It could reduce the reaction time and increase
the yield of the products (Table 2). When the reaction was carried out under reflux conditions, it
gave low yields of products and took longer reaction times, while the same reaction was carried
out under ultrasonic irradiation to give excellent yields of products in short reaction times. The
probable explanation for the positive association of irradiation is that the ultrasonic irradiation
could increase the number of active cavitation bubbles and the size of the individual bubbles,
both of which are expected to result in higher maximum collapse temperature and accelerated
respective reaction. Therefore, it was observed that the reaction in the presence of 0.50 mol % of
nano-CdZr4(PO4)6 and under ultrasonic irradiation with the power of 60W gave the best result as
the obtained product with 88% isolated yield during 25 minutes.
Table 2
We examined condensation reaction under ultrasonic irradiation without catalyst. When the
reaction was examined without catalyst, the products were obtained in a moderate to good yields
10

(Table 1). The results demonstrated that the sonication certainly affected the reaction system.
The recycling of nano-CdZr4(PO4)6 catalyst was examined and the results are summarized in
Figure 3. The possibility of recycling of the catalyst is an important process from different
aspects such as environmental concerns, and commercialapplicable processes. In the recycling
procedure of nanocrystalline CdZr4(PO4)6 ceramics, hot CH3OH was added to dilute the reaction
mixture after terminating the reaction. The catalyst was insoluble in the solvent and was
separated by filtering. The reusability of the catalyst was tested for nine runs, providing almost
similar yields of the desired product.
Fig. 3.
Investigations of the reaction scope revealed that various aromatic aldehydes (bearing electron-
withdrawing and electron-donating groups) can be utilized in this protocol (Table 3). It was
shown that aromatic aldehydes with electron-withdrawing groups reacted faster than those with
electron-releasing groups. Meanwhile, it has been observed that better yields are obtained with
substrates having electron-withdrawing groups.
Table 3.
3.3. The proposed reaction mechanism
A proposed mechanism for the reaction is outlined in Scheme 2 via initial imine formation
followed by attack of the sulfur moiety of the thioglycolic acid on the imine carbon followed by
intramolecular cyclization with the expulsion of water giving rise to the cyclized product
thiazolidinone. Based on this mechanism, it is highly probable that the carbonyl groups of
aldehydes and acid have to be activated, which occurs when the carbonyl oxygen is coordinated
11

by nano-CdZr4(PO4)6 (Scheme 2).
Scheme 2.
4. Conclusions
In conclusion, we have developed a simple and highly efficient protocol for the synthesis of
1,3-thiazolidin-4-ones using nano-CdZr4(PO4)6 as an efficient catalyst under ultrasonic
irradiation. High catalytic activity and ease of recovery from the reaction mixture through
filtration or centrifugation methods, and several reuse times without significant losses in
performance are additional eco-friendly attributes of this catalytic system. The remarkable
advantages of this methodology are easy work-up, short reaction times, recycling of the catalyst,
little catalyst loading and use of ultrasonic irradiation as a valuable and powerful technology.
Further investigations of similar protocols are happening in our laboratory.
Acknowledgment
The authors are grateful to University of Kashan for supporting this work by Grant NO:
159196/XXX.
References
12

1. R. K. Rawal, Y. S. Prabhakar, S. B. Katti,E. De Clercq, Bioorg. Med. Chem.13 (2005)
6771–6776.
2. M. L. Barreca, A. Chimirri, L. De Luca, A. M. Monforte, P. Monforte, A. Rao, M.
Zappala`, J. Balzarini, E. De Clercq, C. Pannecouque, M. Witvrouw, Bioorg. Med.
Chem.Lett. 11 (2001) 1793–1796.
3. R. K. Rawal, R. Tripathi, S. B. Katti, C. Pannecouque, E. De Clercq, Bioorg. Med.
Chem.15 (2007) 1725–1731.
4. M. L. Barreca, J. Balzarini, A. Chimirri, E. De Clercq, L. De Luca, H. Dieter Höltje,
MHöltje, A. M. Monforte, P. Monforte, C. Pannecouque, A. Rao, M. Zappala`, J. Med.
Chem. 45 (2002) 5410-5413.
5. A. Rao, A. Carbone, A. Chimirri, E. De Clercq, A. M. Monforte, P. Monforte, C.
Pannecouque, M. Zappala`, Il Farmaco 57 (2002) 747-751.
6. C. V. Kavitha, Basappa, S. N. Swamy, K. Mantelingu, S. Doreswamy,M. A. Sridhar, J. S.
Prasad, K. S. Rangappa, Bioorg. Med. Chem. 14 (2006) 2290–2299.
7. M. Sayyed, S. Mokle, M. Bokhare, A. Mankar, S. Surwase, S.Bhusare, Y. Vibhute,
Arkivoc 2006 (ii) 187-192.
8. M. V. Diurno, O. Mazzoni, E. Piscopo, A. Calignano, F. Giordano, A. Bolognese, J.
Med. Chem. 35 (1992) 2910-2912.
9. M. V. Diurno, O. Mazzoni, G. Correale, I. G. Monterrey, A. Calignano, G. L. Rana, A.
Bolognese, Il Farmaco 54 (1999) 579–583.
10. D. Sriram, P. Yogeeswari, T. G. Ashok Kumar, J Pharm PharmaceutSci. 8 (3) (2005)
426-429.
11. S. Wu, W. Guo, F. Teraishi, J. Pang, K. Kaluarachchi, L. Zhang, J. Davis, F. Dong, B.
13

Yan, B. Fang, Med. Chem. 2 (2006) 597-605.
12. I. Vazzana, E. Terranova, F. Mattioli, F. Sparatore, Arkivoc 2004 (v) 364-374.
13. M. Cacic, M. Molnar, B. Sarkanj, E. Has-Schön, V. Rajković,Molecules15 (2010) 6795-
6809.
14. W. Cunico, C. R. B. Gomes, W. T. Vellasco Jr.Mini-Reviews in Organic Chemistry. 5
(2008) 336-344.
15. W. Cunico, C. R. B. Gomes, M. de Lourdes, G. Ferreira, L. R. Capri, M. Soares, S. M. S.
V. Wardell, Tetrahedron Lett. 48 (2007) 6217–6220.
16. T. Srivastava, W. Haq, S. B. Katti, Tetrahedron 58 (2002) 7619–7624.
17. A. Ziarati, J. Safaei-Ghomi, S. Rohani, Ultrason. Sonochem. 20 (2013) 1069–1075
18. R. Pagadala, S. Maddila, S. B. Jonnalagadda, Ultrason. Sonochem. 21 (2014) 472–477.
19. C. Leonelli, T. J. Mason, Chem. Eng. Process. 49 (2010) 885–900.
20. N. C. Eddingsaas, K. S. Suslick. Nature, 444 (2006)163.
21. K. S. Suslick, Science, 247 (1990) 1439-1445.
22. P. D. Neuenfeldt, A. R. Duval, B. B. Drawanz, P. F. Rosales, C. R. B. Gomes, C. M.P.
Pereira, W. Cunico, Ultrason. Sonochem. 18 (2011) 65–67.
23. M. Mamaghani, A. Loghmanifar, M. R. Taati, Ultrason. Sonochem. 18 (2011) 45–48.
24. D. P. Gouvêa, V. D.O. Bareño, J. Bosenbecker, B. B. Drawanz, P. D. Neuenfeldt, G. M.
Siqueira, W. Cunico, Ultrason.Sonochem. 19 (2012) 1127–1131.
25. R. Fazaeli, H. Aliyan, Appl. Catal. A: Gen. 353 (2009) 74–79.
26. A. Javidan, A. Ziarati, J. Safaei-Ghomi, Ultrason. Sonochem. 21 (2014) 1150–1154.
27. N. Gorodylova, V. Kosinova, Z. Dohnalova, P. Belina, P. Sulcova, Dyes Pigm. 98(2013)
393-404.
14

28. J.Safaei-Ghomi, A. Javidan, A. Ziarati, H. Shahbazi-Alavi, J Nanopart. Res. 17 (2015)
338-350.
29. D. Kumar, M. Sonawane, B. Pujala, V. K. Jain, A. K. Chakraborti,Green Chem.15 (2013)
2872-2884.
30. S. M. Sadeghzadeh, F. Daneshfar, J. Mol. Liq.199 (2014) 440-444.
31. S. M. Sadeghzadeh, M. Malekzadeh, J. Mol. Liq. 202 (2015) 46-51.
32. N. Foroughifar, S. Ebrahimi, Chin. Chem. Lett. 24 (2013) 383-391.
33. U. R. Pratap, D. V. Jawale, M. R. Bhosle, R. A. Mane, Tetrahedron Lett. 52 (2011)
1689–1691.
15

Figure captions:
Scheme 1.Synthesis of 1,3-thiazolidin-4-ones using nano-CdZr4(PO4)6
Scheme 2.Schematic mechanism for the catalytic activity of nano-CdZr4(PO4)6 in the synthesis
of titled compound
Table 1.Optimization of reaction conditions using different catalysts
Table 2.Study of the effect of ultrasonic irradiation on the formation of 1,3-thiazolidin-4-ones
Table 3.Synthesis of 1,3-thiazolidin-4-ones using nano-CdZr4(PO4)6 under ultrasonic irradiation
Fig. 1.XRD pattern of nano-CdZr4(PO4)6
Fig. 2. FE-SEM images of nano-CdZr4(PO4)6
Fig 3. Reusability of nano-CdZr4(PO4)6 as catalyst for the synthesis of 4a
16

Table 1. Optimization of reaction conditions using different catalystsa
Entry
1
Solvent (condition)
----
Catalyst (mol)%
H2SO4 (10)
Time (min)
480
480
480
420
420
300
300
180
180
140
140
140
140
25
Yieldb(%)
9
2
H2O(reflux)
EtOH (reflux)
PhMe (reflux)
PhMe (reflux)
THF (reflux)
PhMe (reflux)
EtOH(reflux)
DMF (reflux)
THF (reflux)
PhMe (reflux)
PhMe (reflux)
PhMe (reflux)
PhMe (US)c
PhMe (US)c
PhMe (US)c
PhMe (US)c
PhMe (US)c
H2SO4 (10)
trace
trace
14
3
H2SO4 (10)
4
H2SO4 (10)
nano-SnO (5)
5
19
6
nano-ZrO2 (4)
25
7
nano-ZrO2 (4)
35
nano-CdZr4(PO4)6(0.5)
nano-CdZr4(PO4)6 (0.5)
nano-CdZr4(PO4)6 (0.5)
8
29
9
34
10
11
12
13
14
15
16
17
18
42
nano-CdZr4(PO4)6 (0.3)
53
nano-CdZr4(PO4)6 (0.5)
nano-CdZr4(PO4)6 (0.7)
nano-CdZr4(PO4)6 (0.3)
nano-CdZr4(PO4)6 (0.5)
58
58
83
25
88
nano-CdZr4(PO4)6 (0.7)
--------
25
88
25
51
nano-ZrO2 (4)
25
62
a4-Chlorobenzaldehyde (2 mmol), aniline (2 mmol), thioglycolic acid (2 mmol)
b Isolated yields
c Ultrasonic irradiation (60 W)
17

Table 2.Study of the effect of ultrasonic irradiation on the formation of 1,3-thiazolidin-4-onesa
Entry
Power (W)
Time (min)
Yieldb(%)
1
2
3
4
5
30
40
50
60
70
50
40
30
25
25
53
73
82
88
88
a4-Chlorobenzaldehyde (2 mmol), aniline (2 mmol), thioglycolic acid (2 mmol), nano-CdZr4(PO4)6
(0.5 mol%)
b Isolated yields
18

Table 3. Synthesis of 1,3-thiazolidin-4-ones using nano-CdZr4(PO4)6 under ultrasonic
irradiation
Entry
Aldehyde
2-Cl-C6H4
Product
Time (min)
Yielda%
84
m. p °C [ref]
120-124
1
2
30
30
30
30
30
25
25
25
35
25
4a
4b
4c
4d
4e
4f
2-NO2- C6H4
pyridin-2-yl
3-NO2- C6H4
pyridin-3-yl
4-Cl- C6H4
86
112-114
3
81
152-153 [29]
176-178 [32]
135-137
4
83
5
79
6
88
128-130 [29]
138-140 [29]
132-133 [29]
133-135
7
4-NO2- C6H4
thiophen-2-yl
4-isopropyl- C6H4
88
4g
4h
4i
8
80
9
80
10
C6H5
82
130-132 [32]
4j
aIsolated yields
19

CHO
NH2
O
R
nano-CdZr4(PO4)6
+
+
N
OH
HS
O
PhMe
ultrasonic irradiation
R
S
Scheme 1. Synthesis of 1,3-thiazolidin-4-ones using nano-CdZr4(PO4)6
20

R
R
O
N
+
PhNH2
H
((((
O
((((
HS
OH
R
R
HO
N
HN
O
((((
O
S
S
nano-CdZr4(PO4)6
=
Scheme 2. Schematic mechanism for the catalytic activity of nano-CdZr4(PO4)6 in the synthesis of titled
compound
21

Fig. 1. XRD pattern of nano-CdZr4(PO4)6
22

Fig. 2.FE-SEM images of nano-CdZr4(PO4)6
23

Fig 3. Reusability of nano-CdZr4(PO4)6 as catalyst for the synthesis of 4f
24

Graphical abstract:
25