Copper(II)-complex functionalized magnetite nanoparticles: a highly efficient heterogeneous nanocatalyst for the synthesis of 5-arylidenthiazolidine-2,4-diones and 5-arylidene-2-thioxothiazolidin-4-one

Article abstract of DOI:10.1007/s11243-017-0159-3

Abstract: Magnetite nanoparticles (MNPs) have proved to be a useful support for heterogeneous catalysis. We have synthesized Fe₃O₄ MNPs functionalized with a copper(II) complex, and tested the resulting material as a heterogeneous nanocatalyst. The catalyst was tested for aldol condensation reactions between aliphatic/aromatic aldehydes and rhodanine or thiazolidine-2,4-dione (TZD) derivatives under reflux in ethanol, giving the target products in high yield. Environmentally benign chemistry, short reaction times, simple work-up, excellent yields, and the reusability of the new nanocatalyst are beneficial features of the present study. The nanocatalyst was characterized by scanning electron microscopy, vibrating sample magnetometery, thermogravimetry, X-ray diffraction, and energy-dispersive X-ray analyses. The data showed that the magnetic nanoparticles are super-paramagnetic with a size range of 10–20?nm. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11243-017-0159-3

Transit Met Chem
DOI 10.1007/s11243-017-0159-3
Copper(II)-complex functionalized magnetite nanoparticles:
a highly efficient heterogeneous nanocatalyst for the synthesis
of 5-arylidenthiazolidine-2,4-diones and 5-arylidene-2-
thioxothiazolidin-4-one
1
1
1
2
Malihe Akhavan · Naser Foroughifar · Hoda Pasdar · Alireza Khajeh-Amiri ·
3
Ahmadreza Bekhradnia
Received: 22 March 2017 / Accepted: 26 June 2017
©
Springer International Publishing AG 2017
Abstract Magnetite nanoparticles (MNPs) have proved to
be a useful support for heterogeneous catalysis. We have
synthesized Fe O MNPs functionalized with a copper(II)
Introduction
Five-membered heterocycles including the thiazole nucleus
with two heteroatoms and a carbonyl group on the fourth
carbon, such as rhodanine and thiazolidine-2,4-dione
derivatives, have a wide spectrum of biological and phar-
macological activities [1, 2]. In the past two decades, these
compounds have been found to possess antitumor, anti-
inflammatory, anti-microbial, and antidiabetic properties,
and have found clinical use in medications such as cigli-
tazone, englitazone, rosiglitazone, pioglitazone, epalrestat,
and troglitazone for the treatment of type 2 diabetes mel-
litus. They are also key intermediates for the synthesis of
anti-HIV and anti-ischemic agents [3–5]. Hence, the
molecular modification and pharmacological evaluation of
these molecules have attracted much attention from syn-
thetic chemists and pharmacologists [4].
3
4
complex, and tested the resulting material as a heteroge-
neous nanocatalyst. The catalyst was tested for aldol
condensation reactions between aliphatic/aromatic alde-
hydes and rhodanine or thiazolidine-2,4-dione (TZD)
derivatives under reflux in ethanol, giving the target
products in high yield. Environmentally benign chemistry,
short reaction times, simple work-up, excellent yields, and
the reusability of the new nanocatalyst are beneficial fea-
tures of the present study. The nanocatalyst was
characterized by scanning electron microscopy, vibrating
sample magnetometery, thermogravimetry, X-ray diffrac-
tion, and energy-dispersive X-ray analyses. The data
showed that the magnetic nanoparticles are super-param-
agnetic with a size range of 10–20 nm.
Because of pharmacological and medicinal importance
of rhodanine and thiazolidine-2,4-dione, numerous meth-
ods have been applied for the synthesis of these compounds
and their derivatives, with an extensive range of catalysts
including Alum [6], ionic liquids [7], glycine and sodium
carbonate [8], piperidinium acetate [9], and piperidine [10].
However, currently known methods suffer from one or
more drawbacks, such as low yields, long reaction times,
tedious work-up procedures, toxic residues, special appa-
Electronic supplementary material The online version of this
article (doi:10.1007/s11243-017-0159-3) contains supplementary
material, which is available to authorized users.
&
Naser Foroughifar
n_foroughifar@yahoo.com
ratus, environmentally unfavorable solvents, and a
requirement for excess catalyst. Also, using the amine was
found to be carcinogenic and problematic in the recovery
and reusability of the catalysts [11, 12].
1
2
Department of Chemistry, Tehran North Branch, Islamic
Azad University, Tehran, Iran
Young Researchers and Elites club, Yadegar-e Imam
Khomeini (RAH) Shahre Rey Branch, Islamic Azad
University, Tehran, Iran
Although homogeneous catalysts can provide excellent
activity and selectivity for a variety of reactions, the
problems of catalyst separation from the product mixture
and use of large amounts of organic solvents are the main
weaknesses in their wider industrial utility [13, 14].
3
Department of Medicinal Chemistry and Pharmaceutical
Sciences Research Center, Mazandaran University of
Medical Sciences, Sari, Iran
123

Transit Met Chem
According to the principles of green chemistry, magnetic
nanoparticles (MNPs) offer features such as easy prepara-
tion and functionalization, considerable durability and
reusability, high surface area, low toxicity, and facile
recovery with the aid of an external magnet [15, 16].
Consequently, the cost of the desired product can be sig-
nificantly diminished by the use of MNP catalysts.
Moreover, the heterogenization of homogeneous catalysts
on solid supports is a significant field of research in
catalysis.
comparison of their melting points and spectral data with
1
those reported in the literature. HNMR (400 MHz) and
1
3
CNMR (100 MHz) spectra were recorded with a Bruker
Advance spectrometer with CDCl or DMSO-d as solvent
3
6
and TMS as an internal standard. TLC was performed on
silica gel poly gram SILG/UV 254 nm plates. The X-ray
diffraction (XRD) pattern of the catalyst was recorded with
an X-Pert Pro instrument (Cu kα radiation, λ = 1.54 A) in
the region of 2ϴ = 20°–80°. Magnetite properties of the
nanocatalyst were analyzed using a varying magnetic field
from −10000 to 10000 on a BHV-S5 vibrating sample
magnetometer (VSM). Thermogravimetric analysis curves
were carried out using a PL-STA 1500 device manufac-
tured by Thermal Sciences. Thermal analyzer with heating
In recent years, functionalized MNPs have been used in
magnetic resonance imaging, drug delivery systems, cell
biology, biotechnology, protein separation, and cancer
treatments [17, 18]. They have also been applied in various
organic reactions such as Knoevenagel condensation,
Suzuki and Heck cross-coupling, asymmetric aldol reac-
tion, asymmetric hydrogenation of aromatic ketones,
reduction of nitro aromatic compounds, cyanosilylation of
carbonyl compounds, and enantioselective direct addition
of terminal alkynes to imines [19]. Thus, homogeneous
catalysts have various benefits but heterogeneous catalysts
are widely applied due to their easy recovery [20]. The
advantages of magnetic heterogeneous catalysts, especially
involving copper supported on MNPs, include efficiency,
enhanced stability and magnetic retrieval and reuse of the
catalyst [21].
−
1
rate of 10 °C min over a temperature limited area of 30–
1300 °C under N atmosphere. Morphology was analyzed
2
by SEM (Hituch S4160 scanning electron microscope).
Preparation of Fe O MNPs
3
4
3
+
Fe O MNPs were synthesized via co-precipitation of Fe
3
4
2
and Fe in ammonia solution as follows [24]. FeCl ·6H O
+
3
2
(0.86 g, 3.2 mmol) and FeCl ·4H O (0.31 g, 1.6 mmol)
2
2
were dissolved in distilled water (300 ml). The solution
was stirred at 90 °C for 1 h under N atmosphere. Then
2
ammonia solution was added dropwise until pH 11, and the
suspension was stirred for 1 h. The prepared Fe O MNPs
Recently, a copper(II)-catalyst for the Michael–aldol
reaction has been developed [22]. However in spite of high
yields, recycling problems have limited its development.
Therefore, to minimize these disadvantages, the heteroge-
nization of homogeneous catalysts has emerged as a
research focus [23]. With the aim to develop a more effi-
cient catalyst, we herein describe aldol condensation
reactions using various aldehydes and rhodanine or thia-
zolidine-2,4-dione in the presence of a magnetically
reusable and efficacious Fe O @SiO -NH /Cu(II) catalyst
3
4
were isolated from the mixture by applying an external
magnet, washed several times with water, and dried in
vacuum at 60 °C for 5 h.
Preparation of Fe O @SiO
2
3
4
Silica-coated magnetite nanoparticles were prepared by the
St o¨ ber method [24]. Fe O MNPs (1 g) were dispersed in a
3
4
mixture of ethanol (33 ml), distilled water (9 ml), and
concentrated ammonia solution 25% (0.7 ml) by ultrasonic
bath for 30 min. Thentetraethyl orthosilicate (TEOS)
(0.5 ml) was then added dropwise. After vigorous stirring
for 24 h at room temperature, the solid was magnetically
separated, washed sequentially with water (3 9 100 ml)
then ethanol (3 9 100 ml), and dried in vacuum at 60 °C
for 5 h.
3
4
2
2
under Knoevenagel condensation conditions. To the best of
our knowledge, the use of nanoparticle-supported copper
(
II) catalysts for the one-pot synthesis of 5-arylidenthia-
zolidine-2,4-diones and 5-arylidene-2-thioxothiazolidin-4-
one has not been previously reported.
Experimental
Preparation of Fe O @SiO -Cl
3
4
2
Materials and instrumentation
Fe O @SiO -Cl nanoparticles were synthesized with slight
3
4
2
All solvents and reagents were purchased from Merck and
used without additional purification. FTIR spectra were
obtained in the region of 400–4000 cm−1 as KBr pellets
with a PerkinElmer 550 spectrometer. Melting points were
recorded with an Electrothermal 9200 apparatus and are
not corrected. Known products were identified by
modification of the literature procedure [24]. To a sus-
pension of Fe O @SiO (1 g) in dry toluene (100 ml),
3
4
2
3-chloropropyltrimethoxysilane (CPTMS) (1 ml) was
added and the mixture was sonicated for 30 min under N2
atmosphere. Then, the mixture was stirred for 12 h under
reflux and the resulting solid (Fe O /SiO -Cl) was
3
4
2
1
23

Transit Met Chem
separated and washed with toluene (3 9 100 ml) then
ethanol (3 9 100 ml) and finally dried under vacuum at
the required time (Table 2). The progress of the reaction
was monitored by TLC (n-hexane/EtOAc, 2:1). After
completion of the reaction, EtOH (3 ml) was added and the
nanocatalyst was separated by an external magnet. The
crude product was recrystallized from EtOH.
6
0 °C for 5 h.
Preparation of Fe O @SiO -NH
2
3
4
2
Fe O @SiO -NH nanoparticles were synthesized by a
3
Spectroscopic data for the compounds
4
2
2
modified literature procedure [24]. Fe O @SiO -Cl (1 g)
2
3
4
was suspended in acetonitrile (100 ml) with sonication for
Thiazolidine-2,4-dione White crystals (94%); m.p. 126–
127 °C; IR: 3468(M), 3444(M), 2963(W), 2823(W), 1736
(S), 1653(S), 1391(W), 1341(M), 1227(M), 1162(S), 890
3
7
3
0 min. Then, KI (0.27 g, 7 mmol) and K CO (0.96 g,
2 3
mmol) were added and the mixture was sonicated for
0 min. Next, 1,3-diaminopropane (0.52 g, 20 mmol) was
−
1 1
(M), 806(M), 788(M), 715(M), 617(M), 513(M) cm ; H-
added under stirring and the mixture was refluxed for 10 h.
The resulting solid was separated magnetically, washed
with water/ethanol (20 ml/20 ml), and dried under vacuum
at 60 °C for 5 h.
NMR (400 MHz,CDCl ): δ (ppm) 4.07 (s, 2H, CH2), 8.66
3
1
(brs, 1H, NH); C-NMR (100 MHz, CDCl ):38.6, 169.2,
3
3
173.5.
2-thioxo-thiazolidine-4-one (rhodanine) Yellow crystals
(
92%); m.p. 168–169 °C; IR: 3468(W), 3135(W), 3039
W), 2703(W), 1731(S), 1643(S), 1395(M), 1347(M), 1205
M), 1174(M), 897(W), 876(W), 788(W), 787(W), 662(W),
Preparation of Fe O @SiO -NH /Cu(II)
3
4
2
2
(
(
Fe O @SiO -NH (1 g) was added to a solution of
3
4
2
2
−1 1
5
42(W) cm ; H-NMR (400 MHz, CDCl ): δ (ppm) 4.26
3
Cu(OAc) .H O (0.29 g, 1.5 mmol) in ethanol (50 ml). The
2
2
13
s, 2H, CH2), 12.88 (bs, 1H, NH); C-NMR (100 MHz,
(
mixture was sonicated for 30 min, then refluxed for 10 h.
The separated Fe O @SiO -NH /Cu(II) was washed with
CDCl ): 40.6, 175.5, 201
3
3
4
2
2
methanol and dried under vacuum at 60 °C for 5 h.
(Z)-5-Benzylidene-thiazolidine-2,4 -dione(1a) m.p. 251–
2
52 °C; IR: 3459(W), 3899(M), 1688 (S), 600-800 (W),
−1 1
Preparation of 2,4-thiazolidinedione
3136 (S) cm ; H-NMR (400 MHz, DMSO-d ): δ (ppm)
6
7
.52–7.61 (m, 5H, ArH), 7.2 (s, 1H, = CHAr), 10.62 (brs,
1
3
Chloroacetyl chloride (7.02 g, 60 mmol) and thiourea
1H, NH); C-NMR (100 MHz, DMSO-d ):125.3, 127.9,
6
(
4.56 g, 60 mmol) were dissolved in distilled water (10 ml).
131.7130, 137, 143.5, 168.3, 170.1
The mixture was stirred for 20 min to form a white pre-
cipitate. Concentrated hydrochloric acid (6 ml) was then
added and the mixture refluxed for 7–8 h. The product was
filtered off, washed with water (20 ml), and dried under
vacuum. Yield 6.61 g (90%).
(
Z)-5-Benzylidene-2-thioxo-thiazolidine-4-one (2a) m.p.
2
3
7
1
1
10–212 °C; IR: 3193(M), 1237(M), 1728(S), 600-800(W),
−1 1
018(S) cm ; H-NMR (400 MHz, DMSO-d ): δ (ppm)
6
.50–7.60 (m, 5H, ArH),7.7 (s, 1H, = CHAr), 10.89 (bs,
3
1
H, NH); C-NMR (100 MHz, DMSO-d ):124.9, 128.1,
6
32.2, 130.1, 136.8, 143.9, 168.9, 196.5
Preparation of rhodanine
(Z)-5-(4-Methoxybenzylidene)-thiazolidine-2,4-dione (3b)
Carbon disulfide (5 ml) was added to ammonia solution
m.p. 218–220 °C; IR: 3383 (M), 1732(M), 1694(S), 600–
800(W), 3218(S), 1184(M) cm ; H-NMR (400 MHz,
−1
1
(
5 ml), and the reaction mixture was stirred for 30 min at
0 °C. The resulting ammonium dithiocarbamate solution
4
CDCl ): δ (ppm) 3.89 (s, 3H, OCH ), 7.01 (m, 2H, ArH),
3
3
was added to a solution of sodium chloroacetate in distilled
water over 5 min. The reaction mixture was allowed to
stand for 20–30 min, then added to boiling 6 N hydrochlo-
ric acid (10 ml) and heated at 100–110 °C. The precipitate
was filtered off, washed with water (30 ml), and dried
under vacuum. Yield 10.28 g (94%).
7.49 (m, 2H, ArH), 7.83 (s, 1H, = CHAr), 8.36 (brs, 1H,
1
NH); C-NMR (100 MHz, CDCl ): 56.5, 114.9, 116.4,
3
3
128.1, 128.8, 142.8, 160.1, 167.2, 168.9
(Z)-5-(4-Methoxybenzylidene)-2-thioxo-thiazolidine-4-one
(
4b) m.p. 235–237 °C; IR:3353 (M), 1686(S), 1221(M),
00–800(W),3158(S), 1174(M) cm ; H-NMR (400 MHz,
−1 1
6
CDCl ): δ (ppm) 3.84 (s, 3H, OCH ),7.3 (m, 2H, ArH),
3
3
General procedure for aldol condensation
7
.58 (m, 2H, ArH), 7.91 (s, 1H, = CHAr), 8.72 (brs, 1H,
1
NH); C-NMR (100 MHz, CDCl ): 56.8, 115.1, 116.8,
3
3
To a mixture of thiazolidine-2,4-dione or rhodanine
129.3, 129, 143.1, 161.2, 168.9, 196.3
(
0.13 g, 1 mmol), aliphatic/aromatic aldehyde (1 mmol),
and ethanol (4 ml), a portion of Fe O @SiO -NH /Cu(II)
3
(Z)-5-(4-Hydroxybenzylidene)-thiazolidine-2,4-dione (5c)
m.p. 298–299 °C; IR:3344 (M), 1721(S), 600-800(W),
4
2
2
(
0.15 g) was added and the mixture stirred under reflux for
123

Transit Met Chem
−
1 1
113(S), 3160(S) cm ; H-NMR (400 MHz, DMSO-d ): δ
3
(Z)-5-(2-Chlorobenzylidene)
thiazolidine-2,4-
dione
6
(
ppm) 6.98 (m, 2H, ArH), 7.58 (m, 2H, ArH), 7.86 (s,
(12f) m.p. 182–183 °C; IR:3420(M), 1741(S), 1581(M),
−1 1
1
1
H, = CHAr), 7.28 (s, 1H, ArOH), 10.42 (bs, 1H, NH);
841(S), 2829(S) cm ; H-NMR (400 MHz, DMSO-d ): δ
6
3
C-NMR (100 MHz, DMSO- d ):114.7, 116.5, 127.7,
(ppm): 7.93 (s, 1H, = CH), 7.45-7.93 (m, 4H, Ar–CH),
1
6
3
1
28.9, 146, 160.5, 167.9, 168.7
12.90 (brs, 1H, NH); C-NMR (100 MHz, DMSO-d6):
ppm 116.5, 127.2, 128.6, 130.1, 131.4, 132.8, 134.4,
(
Z)-5-(4-Hydroxybenzylidene)-2-thioxo-thiazolidine-4-one
167.9172.8
(
6c) m.p. 288–290 °C; IR:3341 (M), 1688 (S), 1173 (M),
−1
1
00-800 (W),3120 (S), 3161 (S) cm ; H-NMR
6
(Z)-5-(4-Flurobenzylidene)-thiazolidine-2, 4-dione (13g)
m.p. 223–224 °C; IR:3203(M), 1724(S), 3023(S), 1125
(
400 MHz, DMSO-d ): δ (ppm) 7.2 (m, 2H, ArH), 7.63 (m,
6
−1 1
2
H, ArH), 7.86 (s, 1H, = CHAr), 7.44 (s, 1H, ArOH), 10.7
3
(S) cm ; H-NMR (400 MHz, DMSO-d ): δ (ppm): 7.41
6
1
(
bs, 1H, NH); C-NMR (100 MHz, DMSO-d ):115.8,
(m, 2H, ArH), 7.73 (m, 2H, ArH), 7.84 (s, 1H, = CHAr),
1
6
3
1
16.9, 128.0, 129.7, 145.0, 160.0, 167.5, 196.4
12.56 (br s, 1H, NH); C-NMR (100 MHz, DMSO-d6):
1
1
16, 115.9 (2C), 129.5 (2C), 131.3, 140.5, 164.5,
68.1169.0
(
(
(
(
Z)-5-(1H-Indol-3- yl methylene)-thiazolidine-2, 4- dione
7d) m.p. 185–186 °C; IR:3225(M), 1687(S), 600-800
−1
1
W), 3112(S) cm ; H-NMR (400 MHz, DMSO-d ): δ
(Z)-5-(4-Flurobenzylidene)-2-thioxo-thiazolidine-4-one (14g)
m.p. 219–220 °C; IR:3210(M), 1235(M), 1694(S), 1580 M
(S), 1120(S) cm ; H-NMR (400 MHz, DMSO-d ): δ
(ppm): 7.38 (m, 2H, ArH), 7.71 (m, 2H, ArH), 7.67 (s,
1
1H, = CHAr), 13.50 (brs, 1H, NH); C-NMR (100 MHz,
6
ppm) 6.99 (s, 1H, = CHAr), 7.019 (m, 1H, ArH), 7.38 (m,
−1
1
1
1
H, ArH), 7.54 (m, 1H, ArH) 7.71(m, 1H, ArH), 12.01 (brs,
6
1
3
H, NH), 13.2 (brs, 1H, NH(indole)); C-NMR (100 MHz,
3
DMSO-d ): 110, 111.1, 119, 120.1, 121.9, 122.2, 126.0,
6
1
30.8, 135.0, 143.5, 167.3, 168.1
Z)-5-(1H-Indol-3-yl-methylene)-2-thioxo-thiazolidine-4-
one(8d) m.p. 306–307 °C; IR: 3235 (M), 1716(S), 1178
DMSO-d ): ppm 116.4, 115.9 (2C), 129.5 (2C), 131.3,
6
140.5, 165.5, 169.7, 191.8.2.8.17
(
(Z)-5-((Quinoxalin-3-yl) methylene) thiazolidine-2,4-dione
−
1
1
(
M), 600–800(W), 3053(S)cm ; H-NMR (400 MHz,
(15h) m.p. 288–290 °C; IR:3452(M), 1732(S), 2964(S),
−
1 1
DMSO-d ): δ (ppm) 6.99 (s, 1H, = CHAr), 7.09 (m, 1H,
1398(M),2919(S) cm ; H-NMR (400 MHz, DMSO-d ): δ
6
6
ArH), 7.37 (m, 1H, ArH), 7.54 (m, 1H, ArH) 7.71(m, 1H,
(ppm): 7.92-8.17(m, 4H, ArH), 7.59 (s, 1H, = CHAr), 9.31
1
3
ArH), 11.01 (bs, 1H, NH), 13.02 (brs, 1H, NH(indole));
1
(s, 1H, = CHN), 12.65 (brs, 1H, NH);
C-NMR
3
C-NMR (100 MHz, DMSO-d ): 108.6, 11.8, 1203, 121.3,
(100 MHz, DMSO-d ): ppm 124.06, 129.27, 129.48, 129.6,
6
6
1
22.3, 124.5, 126.8, 128.8, 136.1, 144, 168.3, 194.6
131.73, 131.4, 141.76, 142.25, 1438.1, 148.8, 167.3, 168.5
(
Z)-5-((Thiophen -2-yl) methylene)-thiazolidine-2,4- dione
(Z)-5-((Quinoxalin-3-yl) methylene)-2-thioxothiazolidin-
(
9e) m.p. 240–242 °C; IR:3198(M), 1727(S), 665
one (16h) m.p. 295–296 °C; IR:3321(M),1654(M), 1732
(S), 2094(S), 1395(M) cm ; H-NMR (400 MHz, DMSO-
−
1
1
−1 1
(
W) 3056(S) cm ; H-NMR (400 MHz, DMSO-d ): δ
6
(
ppm), 7.27 (d, 1H, ArH), 7.43 (d, 1H, ArH), 7.69 (d, 1H),
1
d ): δ (ppm) 7.91-8.16(m, 4H, ArH), 7.5 (s, 1H, = CHAr),
6
3
13
9.30 (s, 1H, = CHN), 12.60 (brs, 1H, NH); C-NMR
8
.05(s, 1H, = CH), 13.67 (s, 1H, NH);
C-NMR
(
100 MHz, DMSO-d ): 123.1, 124.8, 129.3, 134.37,
6
(100 MHz, DMSO- d ): ppm 124.05, 129.27, 129.48, 129.5,
6
1
35.44, 137.5, 167.5, 169.9
Z)-5-((Thiophen-2-yl) methylene)-2-thioxothiazolidin-4-
one (10e) m.p. 214–215 °C; IR:3128(M), 1728(S), 1171
131.71, 131.2, 141.75, 142.24, 143.2, 148.75, 168.3, 192.5
(
(Z)-5-((Naphthalen-3-yl) methylene)-2-thioxothiazolidin-
4- one (17i) m.p. 270–272 °C; IR: 3132(M), 1648(M),
1732(S), 1479(M), 2684(S) cm ; H NMR (400 MHz,
−1
1
−1
1
(
M), 667(W) 3055(S) cm ; H-NMR (400 MHz, DMSO-
d ): δ (ppm): 7.27 (d,1H, ArH),7.68 (d,1H, ArH), 7.90 (d,
1
CDCl ): δ (ppm) 7.71–7.82 (m, 3H), 8.10–8.15 (m, 4H),
8.60 (s, 1H), 11.77 (brs, 1H, NH); 13C-NMR (100 MHz,
6
3
1
H, ArH), 8.02(s, 1H, = CH), 10.07 (s, 1H, NH); C-NMR
3
(
100 MHz, DMSO-d ): 123.1, 124.8, 129.3, 134.3, 135.4,
CDCl ): δ (ppm) 123.6, 125.8, 127.3, 127.5, 127.8, 128.7,
6
3
1
37.5, 168.1, 194.4
Z)-5-(2-Chlorobenzylidene)-2-thioxothiazolidin-4-one (11f)
m.p. 218–220 °C; IR:3033(M), 1694(S), 1189(M), 1581
128.8, 130.5, 130.7, 131.5, 132.6, 133.1, 167.8, 192.7
(
(Z)-5-((Naphthalen-3-yl) methylene) thiazolidine-2, 4-
dione (18i) m.p. 252–253 °C; IR:3223(M), 1739(S), 1698
(S), 1580(M),2094(S) cm ; H-NMR (400 MHz, CDCl ):
−1
1
−1 1
(
M), 1465(M), 849(S), 1038(W), 2829(S) cm ; H-NMR
3
(
400 MHz, DMSO-d ): δ (ppm) 7.23–7.48 (m, 4H, Ar–
δ (ppm) 7.70–7.76 (m, 3H), 7.94–8.08 (m, 4H), 8.50 (s,
6
1
3
CH), 7.79–7.91 (s, 1H, = CH), 13.7 (brs, 1H, NH); C-
13
1H), 12.65 (brs, 1H, NH); C-NMR (100 MHz, CDCl ):δ
3
NMR (100 MHz, DMSO-d ): 116.1, 126.5, 127.5, 129.4,
(ppm) 123.7, 125.9, 127.1, 127.6, 127.9, 128.6, 128.9,
6
1
29.9, 133.4, 143.5, 168.7, 193.5
130.6, 130.8, 131.7, 132.7, 133.2, 167.5, 168.9
1
23

Transit Met Chem
(Z)-5-(3-Methylbutylidene) thiazolidine-2,4 -dione (19j)
complexation of the Fe O @SiO -NH was performed by
3 4 2 2
m.p. 166–167 °C; IR:3343 (M), 1732(S), 1685 (S), 2963
reaction with excess Cu (OAc) ·H O.
2
2
−
1 1
(
W) cm ; H-NMR (400 MHz, CDCl ): δ (ppm) 1.21 (d,
3
6
8
H), 1.78–1.82 (m, 1H), 2.17–2.18 (m, 2H), 6.82 (t, 1H),
FTIR spectroscopy
FTIR spectra of Fe O , Fe O @SiO , Fe O @SiO -Cl, Fe
3-
1
3
.67 (brs, 1H, NH); C-NMR (100 MHz, CDCl ): 25.51
3
(
2C), 27.55, 40.25, 70.91, 126.01, 136.1, 166.95, 167.63
3
4
3
4
2
3
4
2
O @SiO -NH and Fe O @SiO -NH /Cu(II) are shown in
4
2
2
3
4
2
2
(
Z)-5-(3-Methylbutylidene)-2-thioxothiazolidin-4- one (20j)
Fig. 1. The band at 573 cm− is typical of structural Fe–O
vibrations. A broad absorption band at 3386 cm− is assigned
to –OH groups on the Fe O surface (Fig. 1a). For the Fe
1
m.p. 188–189 °C; IR: 3142 (M), 1655(M), 1725(S), 2964
(
1
−1 1
W) cm ; H-NMR (400 MHz, DMSO-d ): δ (ppm) 1.2–
6
3
4
3-
1
6
.22(d, 6H), 1.74–1.82 (m, 1H), 2.17–2.18 (m, 2H), 6.92–
O @SiO nanoparticles, a sharp band at 1072 cm− is
1
1
.88 (t, 1H), 9.4 (brs, 1H); C-NMR (100 MHz, DMSO-
3
4
2
attributed to Si–O-Si asymmetric stretching vibrations, indi-
d6): 25.5 (2C), 27.5, 40.2, 70.9, 126.0, 136.0, 167.9, 192.6
cating the presence of a SiO layer around the Fe O core.
2
3 4
Peaks at around 960 and 3736 cm− are assigned to Si–OH
moieties (Fig. 1b). The presence of C-H stretching modes
assigned to the propyl groups in Fig. 2c, d is confirmed by
1
Results and discussion
−1
stretching vibrations at about 1459 and 2927 cm , while
peaks at 3421 and 1508–1551 cm− are assigned to the
stretching and bending vibrations of the amino groups
1
Catalyst preparation and characterization
The new magnetically recoverable catalyst Fe O @SiO -
−1
3
4
2
(Fig. 1c, d). The band at 1551 cm shifted to lower frequency
−1
NH /Cu (II) was prepared as shown in (Scheme 1). Firstly,
2
1504 cm , upon reaction of the amine with Cu(OAc) . Also,
2
−1
2
+
Fe O (MNPs) were synthesized by co-precipitation of Fe
3
3
and Fe from ammonia solution. The surface of the Fe O
new absorption bands at516 and470 cm areassignedto Cu–
4
+
3
4
N and Cu–NH bands (Fig. 1e), suggesting that the Fe O @-
3 4
MNPs was then coated with a silica shell by the hydrolysis
and condensation of tetraethyl orthosilicate in ethanol/am-
monia mixture to produce Fe O @SiO . Next, chloropropyl
SiO -NH /Cu(II) was synthesized successfully.
2 2
3
4
2
XRD study
The crystalline structure of Fe O @SiO -NH /Cu(II) was
modified Fe O @SiO (Fe O @SiO -Cl), Fe O @SiO was
3
4
2
3
4
2
3
4
2
prepared by reaction of chloropropyl triethoxysilane. Fe3-
O @SiO -NH was synthesized via the substitution of
3
4
2
2
4
2
2
examined by X-ray diffraction (Fig. 2). According to
Fe O @SiO -Cl with excess 1,3-propanediamine. Finally,
3
Fig. 2, diffraction peaks observed at 2Ɵ = 30.1º, 35.6º,
4
2
Scheme 1 Synthetic pathways
for the synthesis of
3 4 2 2
Fe O @SiO -NH /Cu(II)
123

Transit Met Chem
spinel ferrite core structure during the Fe O @SiO -NH /
3
4
2
2
Cu(II) coating process. Through the Debye–Scherrer for-
mula (D = K λ/βcosƟ), the average crystalline size of
Fe O @SiO -NH /Cu (II) particles was determined. D, k,
3
4
2
2
λ, β, Ɵ in this formula, signify mean grain size, Scherrer’s
constant, X-ray wavelength, corrected diffraction line full-
width at half-maximum (FWHM) and Bragg diffraction
angle, respectively. The average size of Fe O @SiO -NH /
3
4
2
2
Cu(II) was determined as about 13 nm for the width of the
peak at 2Ɵ = 35.6º (311), which is smaller than the value
determined by SEM analysis.
SEM study
Fig. 1 FTIR spectra of (a) Fe
Cl (d) Fe /SiO -NH (e) Fe
3
O
4
NPs (b) Fe
3
O4/SiO
2 3 4 2
(c) Fe O /SiO -
Scanning electron microscopy is very useful for the char-
acterization of surface morphology and size of the MNPs.
The SEM image of the as-prepared Fe O @SiO -NH /Cu
3
O
4
2
2
3
O
4
@SiO
2
-NH
2
/Cu(II) (KBr pellet)
3
4
2
2
(II) is shown in Fig. 3. The particles have a mean diameter
of about 13-20 nm, and most are almost spherical in shape.
EDAX study
EDAX analysis was used to get some information on the
elemental composition and distribution on the surface of
the Fe O @SiO -NH /Cu(II). Thus, Fe, O, Si, C, N, and
3
4
2
2
Cu were detected based on the results in Fig. 4. The
obvious presence of a Cu signal in the EDAX spectrum
demonstrates that Cu(II) was immobilized onto the surface
of the diamine-functionalized MNPs. According to the
above analysis, it can be concluded that the Fe O @SiO -
Fig. 2 XRD diffraction pattern of Fe
O
3 4
@SiO -NH
2
2
/Cu(II)
3
4
2
NH /Cu(II) MNPs have been successfully synthesized.
2
4
3.3º, 53.7º, 57.2º, 63.1º, 74.2º can be assigned to the
220), (311), (400), (422), (511), (440) and (533) planes of
Fe O , respectively, matching well with the standard pat-
(
TGA study
3
4
terns of spinel ferrites available in the literature (JCPDS
file No. 19-0629). This shows the survival of the crystalline
The stability of the Fe O @SiO -NH /Cu(II) and the bond
3 4 2 2
formation between Fe O @SiO -NH and copper(II) were
3
4
2
2
3 4 2 2
Fig. 3 SEM images of Fe O @SiO -NH /Cu(II)
1
23

Transit Met Chem
3 4 2 2
Fig. 6 Magnetization curves of Fe O @SiO -NH /Cu(II). Left inset:
the magnified field from −3 to 3 Oe. Right inset: dispersal of the
MNPs in solvent and capture by an external magnet
3 4 2
Fig. 4 Energy-dispersive X-ray (EDX) spectrum of Fe O @SiO -
2
NH /Cu(II)
examined by thermogravimetric analysis (Fig. 5). The
TGA measurements were taken using a weighed powder
sample of 5–10 mg in a platinum pan, with the results
shown in Fig. 5. The sample was heated from 30 to 1300 °
C at a heating rate 15 °C/min under a nitrogen stream. The
weight loss below 230 °C is attributed to loss of adsorbed
water and or water formed by the condensation of hydroxyl
groups [25]. A weight loss at approximately 230–650 °C is
attributed to decomposition of organic groups grafted to the
surface the MNPs. A weight loss between 650 and 1218 °C
can be ascribed to the decomposition of the residual
structure. According to the TGA curve, the amount of
organic moiety was about 5.5% and inorganic moiety was
about 4.5% against the total heterogeneous catalyst [25].
magnetization (Mr). According to Fig. 6, the saturation
magnetization quantity was 27 emu/g. Hence because of
the silica coating, the functionalized magnetic nanoparti-
cles have a lower magnetic quantity compared with bar
magnetic nanoparticles (74.3 emu/g). On the basis of Fig. 6
(left inset), we can also see that Mr and Hc are negligible;
hence, the Fe O @SiO -NH /Cu(II) MNPs can be regar-
3
4
2
2
ded as super-paramagnetic. According to Fig. 6 (right
inset), the MNPs were effectively attracted with an external
magnet. These results show that the MNPs have excellent
magnetic response, which prevents composite micro-
spheres from aggregating and making them to redisperse
rapidly in case of magnetic field removal.
Catalytic synthesis of rhodanine and TZD
derivatives
Magnetic study
The magnetic properties of the Fe O @SiO -NH /Cu(II)
3
4
2
2
The catalytic properties of the Fe O @SiO -NH /Cu(II)
2
3
4
2
MNPs were determined using a vibrating sample magne-
tometer (VSM) at room temperature (Fig. 6). The
hysteresis curve allows designation of the saturation mag-
netization (Ms), coercivity (Hc), and remanent
catalyst were evaluated for the aldol condensation reaction
between rhodanine or thiazolidine-2,4-dione and diverse
aldehyde derivatives (Scheme 2).
In our initial experiments, a mixture of rhodanine or
thiazolidine-2,4-dione (1 mmol), benzaldehyde (1 mmol),
and catalyst (0.125 g) in ethanol under reflux conditions
was stirred for a specified time, as required to complete the
reaction (100 min). To optimize the conditions, the reaction
was carried out in diverse solvents, using different tem-
peratures. These experiments showed that ethanol is the
most favorable solvent, due to its efficiency and environ-
mental compatibility. Next, the quantity of catalyst was
optimized (Table 1). In the absence of the catalyst, no
product was detected and the starting materials were
recovered. Optimal yields were obtained with 0.15 mg of
the catalyst; higher amounts gave no further improvement.
When aldehydes and rhodanine or thiazolidine-2,4-dione
3 4 2 2
Fig. 5 TG analysis spectra of the Fe O @SiO -NH /Cu(II)
123

Transit Met Chem
Scheme 2 Synthesis of
rhodanine and TZD derivatives
3 4 2 2
using Fe O @SiO -NH /Cu(II)
Y = O, 2,4-thiazolidinedione;
Y = S, rhodanine
Table 1 Aldol condensation of
benzaldehyde (1 mmol),
a
Entry
Catalyst (g)
Y
Solvent
Temperature
Time (min)
Yield (%)
rhodanine and thiazolidine-2,4-
dione (1 mmol) in the presence
1
2
3
4
5
6
7
8
9
–
O
S
–
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
100 °C
100 °C
100 °C
Reflux
300
300
30
0
0
–
–
3 4 2 2
of Fe O @SiO -NH /Cu(II)
under different condition
0.150
0.150
0.125
0.125
0.150
0.150
0.150
0.150
0.125
0.125
0.150
O
S
EtOH
EtOH
EtOH
EtOH
97
95
95
93
79
75
78
76
25
20
85
45
O
S
85
100
160
175
150
170
250
250
30
O
S
CH
CH
3
CN
CN
3
O
S
methanol
methanol
10
11
12
13
a
O
S
EtOH-H
EtOH-H
EtOH
2
O (1:1)
O (1:1)
2
S
Isolated yields
were condensed under reflux in the presence of Cu(OAc)2
as a homogeneous catalyst, the yield of product was 85%
Table 2 Aldol condensation reaction catalyzed by Fe
NH /Cu(II)
3 4 2
O @SiO -
2
(
Table 1, Entry 13).
Aldehyde
Y
Product Yield (%) M.p. reported
Next, the effect of temperature was investigated, using
0
.15 g of the catalyst (Table 1); reflux temperature was found
O
S
1a
89
88
91
89
90
89
95
93
94
93
95
94
97
95
95
94
89
88
88
88
248–250 [26]
209–211 [26]
217–219 [26]
233–235 [26]
[300 [26]
to give the best results. Overall as shown in Table 1, the
optimum yield was obtained using 0.15 g of catalyst, under
reflux and in ethanol as solvent (entries 3 and 4; yield 97.0%)
With the optimized reaction conditions in hand, the
reactions were explored with aromatic aldehydes contain-
ing both electron-withdrawing and releasing groups,
heteroaromatic aldehydes, and aliphatic aldehydes
2a
O
S
3b
4b
O
S
5c
6c
287–290 [26]
180–184 [27]
307–309 [27]
239 [27]
O
S
7d
8d
(
Table 2). All of these condensations gave very good
O
S
9e
yields, with reaction times ranging from 25 to 45 min.
A comparison of the results obtained in this study with
some published procedures is given in Table 3. These
10e
11f
12f
13g
14g
15h
16 h
17i
18i
19j
20j
213–214 [27]
217–220 [26]
180–182 [26]
220–223 [26]
217–219 [26]
Not reported
Not reported
250–251 [28]
269–270 [28]
Not reported
189 [29]
O
S
results show that Fe O @SiO -NH /Cu(II) compares
3
4
2
2
O
S
favorably, with high yields, short reaction times, and
simple conditions.
O
S
The possible reaction pathway for the aldol condensation
mediated by Fe O /SiO -NH-ligand-Cu(II) as a Lewis acid
3
4
2
0
is outlined in Scheme 3. Electron deficient sites on the sur-
face of the catalyst could coordinate with the O-donor sites of
rhodanine or thiazolidine-2,4-dione and activate them for
conversion to the enol form. Subsequent aldol type con-
densation leads to the corresponding product [7, 33].
S
O
S
1
23

Transit Met Chem
Table 3 Comparison of the
catalytic activity of
Entry
Catalyst/Conditions
Time (Min)
Yield (%)
Ref.
a
2-HEAP /solvent-free
3 4 2 2
Fe O @SiO -NH /Cu(II) with
1
2
3
4
5
6
7
8
9
a
3–100
10–60
360–780
360
72–93
25–94
50–90
50–81
85–94
57–78
85–90
50–95
88–97
[30]
[6]
other systems in the
Knoevenagel condensation
Alum/microwave
Base/solvent
[9]
Toluene, Piperidine Reflux
b
[TMG][Lac] /80 °C
[10]
[7]
20–120
240–360
4–8
Pyridine/25–70 °C
[31]
[12]
[32]
This work
BiCl
Piperidine, HOAc/MW
Fe @SiO -NH /Cu(II)
3
/MW
1.5
O
3 4
2
2
20–60
2
-hydroxy ethylammonium propionate
,1,3,3-tetramethylguanidine lactate
b
1
2+
Scheme 3 Plausible mechanism for aldol condensation in the presence Cu organocatalyst Y = O or S
conditions, good yields, inexpensive and simple work-up of
product, and green reaction conditions.
3 4
Table 4 Reusability of the Fe O @SiO2-NH2/Cu(II) MNPs for the
synthesis of 5-arylidenthiazolidine-2,4-diones and 5-arylidene-2-
thioxothiazolidin-4-one conclusion
Acknowledgements The authors thankful the Mazandaran university
of medical sciences for providing laboratory facilities to carry out this
research.
Cycle
1st
98
2nd
98
3rd
96
4th
94
5th
93
6th
92
7th
90
Yield (%)
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