Preparation of thiazolidin-4-one derivatives using ZnO–NiO–NiFe2O4 nano-composite system

Article abstract of DOI:10.1007/s11164-020-04287-5

The hydrothermal synthesis of ZnO–NiO–NiFe₂O₄ nano-composite is reported. The sample was utilized to characterize via XRD, FE-SEM, EDS, FT-IR, UV–Vis, and BET techniques. The sample consisted of three different phases as ZnO (hexagonal), NiO (cubic), and NiFe₂O₄ (cubic) with the average particle size as 34?nm and specific surface area, average pore diameter, and pore volume as 64.35?m²?g^?1, 13.02?nm, and 0.201?cm³?g^?1, respectively. Catalytic behavior of the nano-composite was investigated on the synthesis of thiazolidin-4-one derivatives under thermal and ultrasonic irradiation condition. Our results show that the catalytic activity of ZnO–NiO–NiFe₂O₄ nano-composite is much higher than ZnO, NiO, and NiFe₂O₄ metal oxides. All products were prepared in high yields with short reaction times. In addition, the catalyst was recovered for at least five times.

Full text of DOI:10.1007/s11164-020-04287-5

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04287-5
Preparation of thiazolidin‑4‑one derivatives using
ZnO–NiO–NiFe2O4 nano‑composite system
Mojtaba Lashkari1 · Majid Ghashang2
Received: 25 July 2020 / Accepted: 26 September 2020
© Springer Nature B.V. 2020
Abstract
The hydrothermal synthesis of ZnO–NiO–NiFe2O4 nano-composite is reported.
The sample was utilized to characterize via XRD, FE-SEM, EDS, FT-IR, UV–Vis,
and BET techniques. The sample consisted of three diferent phases as ZnO (hex-
agonal), NiO (cubic), and NiFe2O4 (cubic) with the average particle size as 34 nm
and specifc surface area, average pore diameter, and pore volume as 64.35 m2 g−1,
13.02 nm, and 0.201 cm3 g−1, respectively. Catalytic behavior of the nano-composite
was investigated on the synthesis of thiazolidin-4-one derivatives under thermal and
ultrasonic irradiation condition. Our results show that the catalytic activity of ZnO–
NiO–NiFe2O4 nano-composite is much higher than ZnO, NiO, and NiFe2O4 metal
oxides. All products were prepared in high yields with short reaction times. In addi-
tion, the catalyst was recovered for at least fve times.
Keywords Thiazolidin-4-one · 2-Methyl-5-(4-oxo-2-phenylthiazolidin-3-yl)
thieno[3,4-d]pyrimidin-4(3H)-one · ZnO–NiO–NiFe2O4 nano-composite ·
Hydrothermal synthesis · NiFe2O4
Introduction
Heterocyclic scafolds with N and S heteroatoms have fascinated chemists not
only for the wide variety in their structure but also for their wide array of biologi-
cal properties. As an example, thiazolidinones and thieno[3,4-d]pyrimidine deriva-
tives are known as building blocks in drug design and synthesis and possess various
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04287-5) contains supplementary material, which is available to authorized users.
*
Mojtaba Lashkari
mojtaba_chem_84@yahoo.com; m.lashkari@velayat.ac.ir
1
2
Faculty of Sciences, Velayat University, P.O. Box 9911131311, Iranshahr, Iran
Department of Chemistry, Najafabad Branch, Islamic Azad University, P.O. Box 517,
Najafabad, Iran
Vol.:(0123456789)
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M. Lashkari, M. Ghashang
pharmacological activities [1–4]. The widespread use of structures containing thia-
zolidine nuclei has led scientists to pay special attention to develop the synthesis and
design of chemical structures with thiazolidine nuclei, and for this reason, a num-
ber of methods have been developed for the synthesis of diverse thiazolidine deriva-
tives. Among these reported protocols, those that use the multi-component reaction
of aldehydes, amines, and thioglycolic acid are simple and more favorable due to the
structure diversity, easy to work, and product purifcation [5–13].
On the other hand, metal oxides are a good choice for use as a catalyst in many
chemical reactions due to their thermal and chemical stability and attracted the
attention of chemists for many years. Although metal oxides are useful and appli-
cable materials, the improvement in their characteristics in many cases is necessary
[14, 15]. One way is to make a composite of metal oxides. Composites usually retain
or strengthen the properties of their components. For example, our fndings have
been shown that ZnO-based nano-composites could be used as a more efective cata-
lyst in organic transformations than ZnO alone [16–18]. In particular, composites of
metal oxides have been found to be more suitable materials for use in transportation
industries, lighting and electronics, photometry, and catalytic applications. In addi-
tion, composites have improved properties compared to single-metal oxides [15].
From another view of point, the composites of transition metal ferrites are promis-
ing catalysts for a variety of chemical reactions such as decolorization of an azo
dye, synthesis of amides, partial oxidation of C3H6 to surface carboxylates and NO
oxidation to NO2, synthesis of bis(dihydropyrimidinone)benzene and 3,4-dihydro-
pyrimidin-2(1H)-ones, and vapor phase oxidation of benzoic acid to phenol [19–23].
Magnetic composites are more advantageous compared to non-magnetic materials
as these materials are due to their structural, electronic, high catalytic potentials, and
ease of recovery [24–27]. Thus, the use of metal oxides magnetic composites could
be associated with the environmental and economic impacts.
In the present work, we plan to fabricate ZnO–NiO–NiFe2O4 nano-composite
through a simple hydrothermal synthetic method and evaluation of its catalytic
potential on the preparation of thiazolidin-4-one derivatives.
Experimental section
Preparation of ZnO–NiO–NiFe2O4 nano‑composite
ZnO nano-powders were prepared according to our previous report [28].
In a 250-mL beaker, ZnO nano-powders (1.0 mmol) were dispersed in a
25 mL aqueous solution of FeCl3·6H2O (2.0 mmol) and NiSO4·6H2O (2.0 mmol)
by ultrasonic technique for 60 min. Next, a solution of NaOH (10%) was added
dropwise until the pH = 12. The mixture was sonicated for 60 min and subse-
quently was transferred into an autoclave oven (100 mL) and kept at 200 °C for
24 h. Finally, the prepared ZnO–NiO–NiFe2O4 nano-composite was fltered and
washed with water and dried at 100 °C.
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Preparation of thiazolidin-4-one derivatives using ZnO–NiO–…
General procedure for the preparation of thiazolidin‑4‑one derivatives
To a mixture of amine (1/5, 1.0 mmol), aldehyde (2/6, 1.0 mmol), and thioglycolic
acid (3, 1.0 mmol) in DMF (10 mL) was added ZnO–NiO–NiFe2O4 nano-compos-
ite (0.025 g), and the mixture was refuxed (or sonicated at 100 °C) until the reac-
tion was completed (TLC monitoring). At last, the solvent was concentrated under
reduced pressure and the reaction mixture was purifed using plate chromatography
(silica plates, n-hexane/ethyl acetate 3/1).
Results and discussion
The XRD pattern was used to determine the crystallinity of the ZnO–NiO–NiFe2O4
nano-composite. The XRD pattern shows three phases as ZnO (hexagonal, JCPDS
PDF No. 00-036-1451) with the distinctive peaks as 31.8, 34.4, 36.2, 47.5, 56.6,
62.9, 67.9, and 69.1 [2θ°], NiO (cubic, JCPDS PDF No. 00-002-1239) with the
following distinctive peaks as 37.4, 43.4, 62.2, 75.4, and 79.9 [2θ°], and NiFe2O4
(cubic, JCPDS PDF No. 00-010-0325) designed with the following peaks as 18.4,
30.3, 35.7, 43.4, 57.3, 62.9, and 74.6 [2θ°] without any other phases or impurities
(Fig. 1). The FE-SEM image shows the shapeless morphology of the particles and
shows the uniform distribution of the phases involved in the composite mixture. The
average particle size was determined by the particle size distribution analysis by the
DLS technique, and the results showed that the sample consists of particles of less
than 100 nm in size ZnO–NiO–NiFe2O4. The average particle size determined by
this method was 34 nm. The results of EDS analysis confrm the presence of Zn, Ni,
and Fe elements, and based on the molar ratio of the elements the chemical structure
of nano-composite can be suggested as ZnO–NiO–NiFe2O4 (Fig. 2).
Fig. 1 XRD pattern of ZnO–NiO–NiFe2O4 nano-composite
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M. Lashkari, M. Ghashang
Fig. 2 FE-SEM, EDS, and DLS analysis of ZnO–NiO–NiFe2O4 nano-composite
The FT-IR analysis of ZnO–NiO–NiFe2O4 nano-composite is depicted in Fig. 3.
The sharp signals below 700 cm−1 could be assigned to the stretching vibration
2−
of metal–oxygen bonds. The stretching vibration of the Fe2O4 group is seen as
a broad peak at about 1500 cm−1. The broad peak located at 3300–3700 cm−1 is
related to the stretching vibration of the O–H bond from the adsorbed water on the
KBr disk. At the UV–visible absorption spectra, we found that ZnO–NiO–NiFe2O4
nano-composite discloses absorption at the UV region (Fig. 3). The noticed absorp-
tion peak centered at about 370 nm is due to the existence of the ZnO and NiO
phases in a composite structure of them. The NiFe2O4 phase shows a lower intensity
absorption peak at about 308 nm.
In order to characterize the surface area and possible porosity of
ZnO–NiO–NiFe2O4 nano-composite, nitrogen adsorption–desorption analysis was
used. Figure 3 shows the type IV of isotherm model with an H3-type hysteresis loop
(IUPAC classifcation) that shows the mesoporous structure of the material. The
physicochemical parameters of ZnO–NiO–NiFe2O4 nano-composite including spe-
cifc surface area, average pore diameter, and pore volume were measured by the
BET method as 64.35 m2 g−1, 13.02 nm, and 0.201 cm3 g−1, respectively [29, 30].
Synthesis of thiazolidin‑4‑one derivatives
At frst, the reaction of 5-amino-2-methylthieno[3,4-d]pyrimidin-4(3H)-one
(1.0 mmol), benzaldehyde (1.0 mmol), and thioglycolic acid (1.0 mmol) was
chosen as the model to observe the efect of various solvents (H2O, EtOH,
EtOAc, hexane, Et2O, DMF, and solvent-free condition), catalyst concentrations
1 3

Preparation of thiazolidin-4-one derivatives using ZnO–NiO–…
Fig. 3 FT-IR, UV–Vis, N2 adsorption–desorption isotherm, and pore size distribution analysis of ZnO–
NiO–NiFe2O4 nano-composite
Fig. 4 Reusability of ZnO–NiO–NiFe2O4 nano-composite (preparation of 7a using method A)
(0.01–0.1 g), and diferent metal oxides screening (ZnO, NiO, MgO, Fe2O3,
Al2O3, CaO, Bi2O3, and NiFe2O4) on the product yield. The results are depicted
in Table 1. The product (4a) was formed in low yields in solvents such as EtOH
and EtOAc and in moderate yield under solvent-free condition, while solvents
1 3

M. Lashkari, M. Ghashang
Table 1 Optimization of the reaction conditions (based on the preparation of 2-methyl-5-(4-oxo-2-phe-
nylthiazolidin-3-yl)thieno[3,4-d]pyrimidin-4(3H)-one (4a))
Entry
Catalyst (g)
Condition
Time (h)
Yielda (%)
1
0.025
H2O, Refux
8
–
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
0.025
0.025
0.025
0.025
0.025
0.01
0.05
0.075
EtOH, Refux
EtOAc, Refux
Hexane, Refux
Et2O, Refux
DMF, Refux
DMF, Refux
DMF, Refux
DMF, Refux
DMF, Refux
Solvent-free, 100 °C
US, DMF, 100 °C
DMF, Refux
DMF, Refux
DMF, Refux
DMF, Refux
DMF, Refux
DMF, Refux
DMF, Refux
DMF, Refux
8
8
8
8
3
8
3
2.5
2.5
3
3
3
3
3
3
3
35
41
–
–
95
32
80
83
82
65
97
80
75
25
–
0.1
0.025
0.025
ZnO (0.025 g)
NiO (0.025 g)
MgO (0.025 g)
Fe2O3 (0.025 g)
Al2O3 (0.025 g)
CaO (0.025 g)
Bi2O3 (0.025 g)
NiFe2O4 (0.025 g)
–
–
–
41
3
3
3
aYields refer to the isolated product
Bold values indicate the optimized conditions
such as H2O, hexane, and Et2O are not suitable media for the preparation of the
targeted compounds. Surprisingly, excellent yield (95%) of (4a) was obtained in
dimethylformamide (DMF) as a solvent and using 0.025 g of ZnO–NiO–NiFe2O4
nano-composite as a catalyst. According to the results depicted in Table 1, higher
dosages of the catalyst do not lead to a better yield of product (4a), whereas lower
catalyst dosage resulted in poor yield (32%). Among the metal oxides screened,
ZnO–NiO–NiFe2O4 nano-composite has distinctive better results. The synthesis
of (1d) was done successfully under ultrasonic radiation conditions, and a high
yield of product (97%) was obtained.
After optimization of the reaction condition, the scope and limitations for the
preparation of products 4a–l using other aromatic aldehydes were investigated
(Scheme 1, Table 2). As shown in Table 2, all products were synthesized in high
yields under short reaction times. The reaction of both aldehydes bearing elec-
tron-donating and electron-withdrawing groups results in high yields. However,
electron-withdrawing groups have longer reaction times than those of electron-
donating groups. The generality of the method was also examined under ultra-
sonic irradiation condition. As can be seen from Table 2, all target products were
synthesized in excellent yields.
1 3

Preparation of thiazolidin-4-one derivatives using ZnO–NiO–…
S
O
O
N
O
N
NH2
S
ZnO-NiO-NiFe2O4
nano-composite
O
Ar
HN
H3C
HN
H3C
+ Ar-CHO
+
OH
S
Condition
SH
N
3
2
4a-l
1
Scheme 1 Preparation of 2-methyl-5-(4-oxo-2-arylthiazolidin-3-yl)thieno[3,4-d]pyrimidin-4-(3H)-one
derivatives (4a–l) using ZnO–NiO–NiFe2O4 nano-composite
Table 2 Preparation of thiazolidin-4-one derivatives (4a–l) using ZnO–NiO–NiFe2O4 nano-composite
Entry Ar
Product Method A
Method B
Melting point (°C)
time (h)/Yield (%) Time (h)/Yield (%)
1
2
3
4
5
6
7
8
Ph
4a
4b
4c
4d
4e
4f
3/95
2.5/90
3/83
2.5/87
4/69
3.5/79
4/98
2.5/84
2.5/94
2.5/88
2.5/90
5/78
3/97
2.5/96
3/88
2.5/90
4/79
3.5/93
4/90
120–122
151–153
137–139
144–146
171–173
189–191
197–199
192–194
188–190
211–213
203–205
190–192
4-MeOC6H4
2-MeC6H4
4-MeC6H4
2-ClC6H4
4-ClC6H4
4-BrC6H4
3-ClC6H4
4-(CH3)3CC6H4
3,4-(CH3O)2C6H4
3,4,5-(CH3O)3C6H4 4k
4-NO2C6H4
4g
4h
4i
3/93
9
2.5/91
2.5/89
2.5/88
5/77
10
11
12
4j
4l
Method A: DMF, refux; Method B: US, DMF, 100 °C
ZnO-NiO-NiFe2O4
nano-composite
O
S
O
ArNH2
Ar-CHO
+
OH
+
N
Ar
Ar
Condition
SH
6
5
3
7a-y
Scheme 2 Preparation of thiazolidin-4-one derivatives (7a–y) using ZnO–NiO–NiFe2O4 nano-composite
The method can be extended by the use of diferent amines. In continue, 5-amino-
2-methylthieno[3,4-d]pyrimidin-4(3H)-one was replaced by diferent aromatic
amines and the potential of ZnO–NiO–NiFe2O4 nano-composite was investigated
as a catalyst on the three-component reaction of aromatic amines, aldehydes, and
thioglycolic acid (Scheme 2). Diferent aromatic amines were successfully used in
the reaction, and the corresponding products (7a–y) were obtained in high yields.
The results are shown in Table 3. In general, electron-donating groups substituted
on aromatic rings both in amines and in aldehydes have a positive efect on the reac-
tion rate. Electron-donating groups such as methyl and methoxy increase the rate of
the reaction, while electron-withdrawing groups decrease the rate of the reaction.
1 3

M. Lashkari, M. Ghashang
Table 3 Preparation of thiazolidin-4-one derivatives (7a–y) using ZnO–NiO–NiFe2O4 nano-composite
Entry
ArCHO
ArNH2
Product
Method A
Method B
Time (h)/Yield (%)
Time (h)/Yield (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
7a
7b
7c
7d
7e
7f
7g
7h
7i
2/87
1.8/90
3/81
2/91
1.8/93
3/85
4-MeC6H4
3-NO2C6H4
4-NO2C6H4
4-MeOC6H4
4-ClC6H4
4-BrC6H4
Ph
4-MeC6H4
4-ClC6H4
2-ClC6H4
3-NO2C6H4
4-MeOC6H4
2-ClC6H4
4-NO2C6H4
3-NO2C6H4
2-MeC6H4
4-MeOC6H4
4-MeC6H4
Ph
3/79
3/83
1.5/88
2.5/88
2.5/80
1.5/84
1/89
2/79
2/84
3/87
1/90
2.5/90
3/85
3.5/86
1/89
1/96
1/79
1.5/82
1.5/90
3/81
3/74
2/90
1.5/90
2.5/93
2.5/87
1.5/88
1/94
2/85
2/86
3/90
1/92
2.5/88
3/88
3.5/89
1/94
1/93
1/84
1.5/86
1.5/94
3/76
3/75
2/79
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
3-MeC6H4
3-NO2C6H4
4-NO2C6H4
3-MeOC6H4
4-ClC6H4
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
7j
7k
7l
7m
7n
7o
7p
7q
7r
7s
7t
Ph
Ph
Ph
Ph
7u
7v
7w
7x
7y
Ph
3/88
3/80
Method A: DMF, refux; Method B: US, DMF, 100 °C
Amines substituted with electron-donating groups have more reactivity when com-
pared with those substituted with electron-withdrawing groups.
At last, we demonstrate that the catalyst could be recovered from the reaction
mixture by an external magnet. The catalyst was tested for fve runs without a sig-
nifcant decrease on the reactivity (Fig. 4).
Supplementary data summary
Details of the experimental procedures, characterization data for compounds
1HNMR, 13CNMR, and elemental analysis of selected compounds have been pro-
vided in the Supplementary Data fle.
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Preparation of thiazolidin-4-one derivatives using ZnO–NiO–…
Acknowledgements We gratefully acknowledge fnancial support from the Research Council of the
Velayat University.
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