Nanomagnetically modified polyphosphoric acid (NiFe2O4@SiO2-PPA): An efficient, fast, and reusable catalyst for the synthesis of 2-thioxoquinazolinones under solvent-free conditions

Article abstract of DOI:10.1007/s11164-014-1866-4

Polyphosphoric acid functionalized silica-coated magnetic nanoparticles with core-shell structure (NiFe₂O₄@SiO₂-PPA) has been used as a magnetically recyclable green catalyst for the one-pot three-component synthesis of 2-thioxoquinazolinones by the reaction of isatoic anhydride, primary amines and thiourea under neat conditions. The catalyst is readily recovered by simple magnetic decantation and can be recycled five times with no significant loss of catalytic activity.

Full text of DOI:10.1007/s11164-014-1866-4

Res Chem Intermed
DOI 10.1007/s11164-014-1866-4
Nanomagnetically modified polyphosphoric acid
(NiFe2O4@SiO2–PPA): an efficient, fast, and reusable
catalyst for the synthesis of 2-thioxoquinazolinones
under solvent-free conditions
•
Hossein Eshghi Amir Khojastehnezhad
•
•
Farid Moeinpour Mehdi Bakavoli
•
•
Nafiseh Zeinabi Sadegh Allameh
Received: 8 August 2014 / Accepted: 2 November 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract Polyphosphoric acid functionalized silica-coated magnetic nanoparticles
with core–shell structure (NiFe2O4@SiO2–PPA) has been used as a magnetically
recyclable green catalyst for the one-pot three-component synthesis of 2-thioxo-
quinazolinones by the reaction of isatoic anhydride, primary amines and thiourea
under neat conditions. The catalyst is readily recovered by simple magnetic
decantation and can be recycled five times with no significant loss of catalytic
activity.
Keywords Polyphosphoric acid Á Magnetic nanoparticles Á One-pot, three-
component Á 2-Thioxoquinazolinones Á Isatoic anhydride
Introduction
In recent years, much attention has been directed toward the production of magnetic
nanoparticles (MNPs) [1–3], because these nanoparticles can be well dispersed in
the reaction mixtures without a magnetic field providing large surfaces for ready
access of substrate molecules. More importantly, after completing the reactions, the
MNP catalysts can be isolated efficiently from the product solution through a simple
H. Eshghi Á M. Bakavoli
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
A. Khojastehnezhad Á N. Zeinabi Á S. Allameh
Department of Chemistry, College of Science, Islamic Azad University, Mashhad Branch,
Mashhad, Iran
F. Moeinpour (&)
Department of Chemistry, College of Science, Islamic Azad University, Bandar Abbas Branch,
7915893144 Bandar Abbas, Iran
e-mail: f.moeinpour@gmail.com; fmoeinpour52@iauba.ac.ir
123

H. Eshghi et al.
magnetic separation process. The strategy of magnetic separation, taking advantage
of MNPs, is typically more effective than filtration or centrifugation as it prevents
loss of the catalyst [4, 5]. Magnetic separation of super MNPs is simple,
economical, and promising for industrial applications. From both economic and
environmental viewpoints, organic reactions under solvent-free conditions using
recoverable catalysts have gained significant attention [5–8]. Rostamnia et al.
reported the synthesis of MNPs for immobilizing sulfuric acid as a heterogeneous
catalyst, and showed that their synthesized catalyst can act as a magnetic separable
catalyst and after completing the reaction can be easily isolated by using an external
magnet [9]. In another study, Mamani and et al. reported supporting sulfonic acid on
silica-coated MNPs, and obtained good results in the catalytic activity of these
catalysts [10]. Polyphosphoric acid (PPA) is an inorganic acid which is used as a
catalyst in organic synthesis [11, 12], but because it is homogeneous, its separation
is difficult after completing the reaction. Thus, we decided to support this acid on
silica-coated MNPs.
Thioxoquinazolinones have been the object of intensive investigation due to their
different biological properties such as antimycobacterial [13], antifungal [14],
antihypertensive [15], antihistaminic [16], enzyme inhibitor [17], anticancer [18]
and antiviral activities [19]. Although various procedures have been reported for the
synthesis of thioxoquinazolinone derivatives [20–22], most of the methods have
encountered some drawbacks, such as low yields, prolonged reaction time,
expensive catalysts and use of toxic organic solvents. Thus, the development of
an environmentally benign and high yielding methodology for the synthesis of
thioxoquinazolinones is in great demand.
Recently, we developed approaches for the synthesis of biologically interesting
products via multicomponent reactions [23–26]. The challenge in this field was
developing efficient and rapid green methods. Based on our earlier success in the
preparation of magnetic nanoparticles as catalysts [27–30] combined with our
achievements in this area, we present here the results of an extended investigation
into the activity of the PPA functionalized magnetic nanocatalyst [27] NiFe2O4@-
SiO2–PPA, as an efficient catalyst for the synthesis of 2-thioxoquinazolinones.
Facile separation of the catalyst by using an external magnet and the recyclability of
the catalyst (up to five times) are other important benefits of this system. To the best
of our knowledge, there are no examples of the use of NiFe2O4@SiO2–PPA as a
catalyst for the synthesis of thioxoquinazolinones from the condensation of isatoic
anhydride, primary amines and thiourea under solvent-free conditions. Therefore,
we wish to report a simple, rapid and an efficient synthetic method for the synthesis
of thioxoquinazolinones using NiFe2O4@SiO2–PPA as a heterogeneous and
reusable catalyst without the requirement for any solvent, salt, or additive
(Scheme 1).
Experimental
Melting points were determined on an Electrothermal type 9100 melting point
apparatus. IR spectra were recorded using a 4300 Shimadzu spectrophotometer with
123

Nanomagnetically modified polyphosphoric acid (NiFe2O4@SiO2–PPA)
O
O
S
NiFe2O4 SiO2-PPA
@
NR
O
RNH2
H2N
NH2
Solvent free
N
H
N
H
S
O
3a-o
4a-o
1
2
Scheme 1 Synthesis of thioxoquinazolinones catalyzed by NiFe2O4@SiO2–PPA
KBr plates. 1H NMR spectra were recorded on a Bruker DRX500 spectrometer. The
products (4a–o) were isolated and characterized by comparison of physical and
spectral data with those of known samples.
Preparation of NiFe2O4@SiO2–PPA
The magnetic nanoparticles (NiFe2O4; Fig. 1) were synthesized by a chemical co
precipitation technique using ferric and nickel ions [31]. Based on our previous
report [27], coating a layer of silica on the surface of the NiFe2O4 nanoparticles and
then functionalization of the iron oxide with polyphosphoric acid were achieved by
treatment with tetraethyl orthosilicate (TEOS) followed by polyphosphoric acid. As
shown in Fig. 1, the SEM image of NiFe2O4 nanoparticles demonstrates that these
MNPs are almost spherical and regular in shape. However, aggregation of the
nanoparticles was found and this aggregation might occur during the coating and
supporting process [27–30].
General procedure for the preparation of 3-(aryl)-2-thioxo-2,3-
dihydroquinazolin-4(1H)-ones (4a–i)
A mixture of isatoic anhydride (2.0 mmol), primary amines (2.0 mmol) with
thiourea (2.0 mmol) under solvent-free condition at 120 °C in the presence of
(0.02 g) of NiFe2O4@SiO2–PPA was heated in an oil bath for 18–30 min. Upon
completion, cold ethanol was added to the reaction mixture (the product is soluble in
ethanol) and the NiFe2O4@SiO2–PPA was placed on the side wall of the reaction
vessel with the aid of an external magnet, then the catalyst was washed and dried to
be reused in the next run. The solvent was evaporated and the resulting crude
product was collected and gives compounds (4a–o) in high yields.
The spectral data of some representative 3-(aryl)-2-thioxo-2,3-dihydroquinazo-
lin-4(1H)-ones are the following:
3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one (4a): mp 307–309 °C,1H NMR
(500 MHz, DMSO-d6): d 7.2–8 (m, 9H, Ar–H), 13 (br, 1H, N–H exchanges with
D2O), IR (KBr disc): 1,662 (C=O), 1,229 (C=S), 3,243 cm-1 (N–H).
3-(4-Methylphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one (4d): mp 305–307 °C,
1H NMR (500 MHz, DMSO-d6): d 2.38 (s, 3H, CH3), 7.1–8 (m, 8H, Ar–H), 13 (br,
123

H. Eshghi et al.
Fig. 1 Preparation of polyphosphoric acid supported on NiFe2O4@SiO2–PPA and its SEM image
1H, N–H exchanges with D2O), IR (KBr disc): 1,662 (C=O), 1,199 (C=S),
3,243 cm-1 (N–H).
3-Benzyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one (4e): mp 254–255 °C, 1H NMR
(500 MHz, DMSO-d6): d 5.6 (s, 2H, CH2), 7.2–8 (m, 9H, Ar–H), 13 (br, 1H, N–H
exchanges with D2O), IR (KBr disc): 1,688 (C=O), 1,179 (C=S), 3,200 cm-1
(N–H).
3-(4-Chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one (4f): mp 318–320 °C,
1H NMR (500 MHz, DMSO-d6): d 7.2–8 (m, 8H, Ar–H), 13 (br, 1H, N–H
exchanges with D2O), IR (KBr disc): 1,661 (C=O), 1,233 (C=S), 3,244 cm-1
(N–H).
3-(2-Methylphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one (4 h): mp 265–267 °C,
1H NMR (500 MHz, DMSO-d6): d 2.94 (s, 3H, CH3), 7.1–8 (m, 8H, Ar–H), 13 (br,
1H, N–H exchanges with D2O), IR (KBr disc): 1,662 (C=O), 1,199 (C=S),
3,286 cm-1 (N–H).
Results and discussion
In order to determine the optimum conditions, the reaction between isatoic
anhydride (2.0 mmol), aniline (2.0 mmol) with thiourea (2.0 mmol) at 120 °C were
chosen as a model reaction. The best result has been obtained at 0.02 g of catalyst
(Table 1) and under solvent-free conditions (Table 2). For comparison, and to show
the effect of NiFe2O4@SiO2–PPA as a solid acid catalyst, synthesis of the model
compound 4a, was also investigated using SiO2–PPA, PPA, and SiO2 under solvent
free conditions separately. The results are given in Table 3 and, as shown,
NiFe2O4@SiO2–PPA gave the best result (entry 1). Using SiO2–PPA as the catalyst
123

Nanomagnetically modified polyphosphoric acid (NiFe2O4@SiO2–PPA)
Table 1 Comparison of the
Entry
Catalyst mol% (g)
Time (min)
Yield (%)
amount of NiFe2O4@SiO2–PPA
and yields for synthesis of
3-phenyl-2-thioxo-2,3
dihydroquinazolin-4(1H)-one
(4a)
1
1
1
2
3
4
5
None
120
60
30
30
18
18
18
None
31
0.4 (0.008)
0.5 (0.010)
1.0 (0.020)
2.0 (0.040)
4.0 (0.080)
5.0 (0.10)
54
67
91
92
91
Table 2 Comparison of
different solvents for synthesis
of 3-phenyl-2-thioxo-2,3-
Entry
Solvent
Time (min)
Yield (%)
1
2
3
4
5
6
p-xylene
DMF
180
120
300
120
480
18
79
70
57
41
67
91
dihydroquinazolin-4(1H)-one
(4a) using NiFe2O4@SiO2–PPA
Toluene
DMAC
EtOH
Solvent-free
Table 3 Comparison of various conditions for synthesis of 3-phenyl-2-thioxo-2,3-dihydroquinazolin-
4(1H)-one (4a)
Entry
Catalyst (g)
Time (min)
Yield (%)
1
2
3
4
NiFe2O4@SiO2–PPA (0.04)
SiO2–PPA (0.05)
PPA (0.05)
18
30
30
60
91
84
68
SiO2 (0.10)
No reaction
Isatoic anhydride (2.0 mmol), aniline (2.0 mmol) and thiourea (2.0 mmol) at 120 °C under solvent-free
conditions
gave the product 4a in good yield (84 %) (entry 2), but separation and recovery of
SiO2–PPA were not easy, because we needed filtration or centrifugation, which are
not eco-friendly processes. Also, we used PPA as a catalyst and the yield of the
reaction was relatively good (68 %), but it was not recyclable (entry 3). Therefore,
NiFe2O4@SiO2–PPA can act as a solid acid catalyst in the synthesis of
2-thioxoquinazolinones derivatives. The generality of this process was demon-
strated by the wide range of substituted primary amines to synthesize the
corresponding products in high yields (Table 4). Unlike some previously reported
methods, the present method does not require toxic organic solvents to produce the
2-thioxoquinazolinones derivatives (4a–o). All the products were characterized by
NMR, IR and melting point and also by comparison with the data reported in
literature.
123

H. Eshghi et al.
Table 4 NiFe2O4@SiO2–PPA-catalyzed one-pot synthesis of 3-(aryl)-2-thioxo-2,3-dihydroquinazoli-
none-4(1H)-ones (4a–o)
Entry
R
Producta
Time
(min)
Yield
(%)b
Mp
(°C)
Lit. Mp
(°C)
O
1
18
91
303–304 302 [32]
H2N
N
N
H
S
S
S
4a
r
B
2
25
86
318–320 320 [32]
H2N
r
B
O
N
N
H
4b
e
OM
3
4
22
19
88
79
273–274 274 [32]
H2N
e
OM
O
N
N
H
4c
e
M
299–300 298 [32]
H2N
e
M
O
N
N
H
S
4d
O
5
6
20
18
92
90
254–255 253–254 [33]
318–320 319–321 [33]
H2N
N
N
H
S
4e
Cl
H2N
Cl
O
N
N
H
S
S
S
4f
O
7
8
20
22
89
83
282–284 282–284 [34]
260–262 260–262 [34]
H2N
e
M
N
e
M
N
H
4g
O
H2N
N
e
M
e
M
N
H
4h
123

Nanomagnetically modified polyphosphoric acid (NiFe2O4@SiO2–PPA)
Table 4 continued
Entry
R
Producta
Time
(min)
Yield
(%)b
Mp
(°C)
Lit. Mp
(°C)
O
9
25
88
260–262 261–263 [35]
H2N
N
F
F
N
H
S
4i
NO2
10
11
25
91
328–329 330–332 [36]
H2N
H2N
H2N
NO2
O
N
N
H
S
4j
Cl
30
88
254–256 254–256 [36]
Cl
O
N
Cl
Cl
N
H
S
4k
O
12
13
25
25
85
90
268–269 270–271 [37]
198–199 199–200 [20]
N
N
H
S
4l
N
H2N
H2N
H2N
O
N
N
H
S
S
4m
O
14
15
30
20
87
90
246–248 246–248 [36]
170–172 171–172 [37]
N
N
H
4n
O
N
N
H
S
4o
Isatoic anhydride (2.0 mmol), aniline (2.0 mmol), thiourea (2.0 mmol) and NiFe2O4@SiO2–PPA (0.02 g)
at 120 °C
a
All the products were identified by comparing of their melting points and spectral data (IR and 1H
NMR) with those of authentic samples
b
Isolated yields
123

H. Eshghi et al.
Scheme 2 Plausible reaction mechanism for the synthesis of 2-thioxoquinazolinones in the presence of
NiFe2O4@SiO2–PPA as a catalyst
Fig. 2 VSM curve of NiFe2O4 at r.t
Fig. 3 Reusability of NiFe2O4@SiO2–PPA for the model reaction
123

Nanomagnetically modified polyphosphoric acid (NiFe2O4@SiO2–PPA)
A probable mechanism for condensation of isatoic anhydride, aniline, thiourea
and NiFe2O4@SiO2–PPA (as an acidic catalyst) for the synthesis of 2-thioxoqui-
nazolinones is proposed as shown in Scheme 2.
It is of great importance that the core/shell material should possess sufficient
magnetic and superparamagnetic properties for its practical applications. Magnetic
hysteresis measurements for the NiFe2O4 were done in an applied magnetic field at
r.t., with the field sweeping from -10,000 to ?10,000 Oersted. As shown in Fig. 2,
the M (H) hysteresis loop for the samples was completely reversible, showing that
the nanoparticles exhibit superparamagnetic characteristics. The hysteresis loops of
them reached saturation up to the maximum applied magnetic field. The magnetic
saturation value of the NiFe2O4 is 16.71 emu g-1 at r.t. These particles showed high
permeability in magnetization, and their magnetization was sufficient for magnetic
separation with a conventional magnet (Fig. 2).
At the end of the reaction, to determine the applicability of catalyst recovery,
ethanol was added to the reaction mixture to dissolve the product. With the aid of an
external magnet, the catalyst was held on the side wall of the reaction vessel, while
the solution was decanted. The catalyst was washed with diethyl ether to remove
residual product, dried at 100 °C under vacuum, and reused in subsequent reactions
in excellent yields (91, 91, 91, 90 and 89 %). It showed the same activity as the
fresh catalyst without any significant loss of its activity (Fig. 3).
Conclusion
We have reported a simple new catalytic method for the synthesis of 2-thioxoqui-
nazolinones by one-pot three-component condensation reaction of isatoic anhydride,
primary amines and thiourea using NiFe2O4@SiO2–PPA as an efficient, reusable,
and green heterogeneous catalyst under solvent-free conditions. Moreover, the
catalyst could be readily separated by use of a magnetic force and reused without
any significant loss of catalytic activity after five runs.
Acknowledgment The authors are grateful to Islamic Azad University, Bandar Abbas and Mashhad
Branches for financial support.
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