Magnetic Fe3O4 nanoparticles supported imine/Thiophene-nickel (II) complex: A new and highly active heterogeneous catalyst for the synthesis of polyhydroquinolines and 2, 3-dihydroquinazoline-4(1H)-ones

Article abstract of DOI:10.1002/aoc.3943

A new magnetically separable nickel catalyst (Ni(NO₃)_2?Imine/Thiophene-Fe₃O₄@SiO₂) was readily prepared and structurally characterized by Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDX), Vibrating sample magnetometer (VSM), X-Ray diffraction (XRD) and Atomic absorption spectroscopy (AAS). The Ni(NO₃)_2?Imine/Thiophene-Fe₃O₄@SiO₂ exhibited efficient catalytic activity in the synthesis of 2,3-dihydroquinazoline-4(1H)-ones and polyhydroquinolines. Catalysis research under water and solvent-free conditions makes also this synthetic protocol ideal and fascinating from the environmental point of view. The catalyst can be magnetically recovered after the reaction and can be reused for many times without appreciable decrease in activity.

Full text of DOI:10.1002/aoc.3943

Received: 28 February 2017
DOI: 10.1002/aoc.3943
Revised: 10 May 2017
Accepted: 27 May 2017
F U L L PA P E R
Magnetic Fe3O4 nanoparticles supported imine/Thiophene‐nickel
(II) complex: A new and highly active heterogeneous catalyst for
the synthesis of polyhydroquinolines and 2, 3‐dihydroquinazoline‐
4(1H)‐ones
Lotfi Shiri | Leili Heidari | Mosstafa Kazemi
Department of Chemistry, Faculty of Basic
Sciences, Ilam University, P.O. Box 69315‐
516, Ilam, Iran
A new magnetically separable nickel catalyst (Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2) was readily prepared and structurally characterized by Fourier
transform infrared spectroscopy (FT‐IR), Scanning electron microscopy (SEM),
Energy‐dispersive X‐ray spectroscopy (EDX), Vibrating sample magnetometer
(VSM), X‐Ray diffraction (XRD) and Atomic absorption spectroscopy (AAS).
The Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 exhibited efficient catalytic activity
in the synthesis of 2,3‐dihydroquinazoline‐4(1H)‐ones and polyhydroquinolines.
Catalysis research under water and solvent‐free conditions makes also this syn-
thetic protocol ideal and fascinating from the environmental point of view. The
catalyst can be magnetically recovered after the reaction and can be reused for
many times without appreciable decrease in activity.
Correspondence
Lotfi Shiri, Department of Chemistry,
Faculty of Basic Sciences, Ilam University, P.
O. Box 69315‐516, Ilam, Iran.
Email: lshiri47@gmail.com
Funding information
Ilam University
KEYWORDS
2,3‐dihydroquinazoline‐4(1H)‐ones, magnetically nickel catalyst, magnetically separation,
polyhydroquinolines, solvent‐free condition, water
1 | INTRODUCTION
research in catalysis. Among various solid supports used for
the immobilization of metallic catalysts, magnetic nanoparti-
Catalysis research campaign is a hot research topic in modern
organic synthesis. Compared with the heterogeneous cata-
lysts, homogeneous catalysts exhibit high catalytic activities
in chemical processes due to their solubility in reaction
media, which increases catalytic site accessibility for the sub-
strate.[1,2] However, separating them from the reaction mix-
ture to avoid contamination of the product requires
expensive and tedious purification steps.[3,4] In recent times,
the immobilization of homogeneous catalysts on support
materials (such as inorganic silica and organic polymers),
for incorporate the preponderances of both heterogeneous
and homogeneous catalysis, have emerged as an efficient cat-
alytic strategy to overcome this drawback.[5,6] Therefore, the
search for finding new support materials and
heterogenization techniques is a hot research topic in modern
cles have emerged as a robust and high‐surface‐area hetero-
geneous catalyst support, because they could not only
stabilize the reaction catalytic species, but also improve the
catalytic activity[7–12] The simple separation of MNPs‐sup-
ported catalysts from products or mixture reaction by an
external magnet is the most notable advantage of magnetic
nanoparticles.[13–15] It is noteworthy that magnetic‐supported
catalysts can be reused many times while keeping their initial
activity. Among the various employed magnetic NPs as the
core magnetic support, Fe3O4 nanoparticles have been widely
studied both for their scientific interests and technological
applications.[15] In describing the magnetic nanoparticles
can be said that in fact the magnetic separation is an admira-
ble and valuable victory in the research campaign of chemis-
try catalysis.
Appl Organometal Chem. 2017;e3943.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.3943

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SHIRI ET AL.
In recent times, catalysis research under green mediums
antidiabetic, antibacterial, antidefibrillatory, antipyretic, and
anticonvulsant agents.[22–30] Polyhydroquinolines also are
well‐known drugs for the treatment of cardiovascular and
Alzheimer's diseases.[31,32] Furthermore, polyhydroquinoline
derivatives are well‐known as Ca2+ channel blockers and
drugs of NADH co‐enzymes.[33,34] The biological and phar-
maceutical activities of 2,3‐dihydroquinazoline‐4(1H)‐one
and polyhydroquinoline derivatives have encouraged organic
chemists to develop numerous one‐pot, green strategies for
their preparation. In recent times, search for finding new
or in the absence of solvent has received special attention in
both academic and industrial research.[16]
2,3‐dihydroquinazoline‐4(1H)‐ones and polyhydro-
quinolines are two important category of nitrogen‐containing
heterocyclic compounds that are broadly distributed in many
natural products and bio‐active molecules.[17–21] 2, 3‐
dihydroquinazoline‐4(1H)‐one and polyhydroquinoline
structural motifs have been known to possess diverse biolog-
ical activities such as antitumor, anticancer, antibiotic,
SCHEME 1 Stepwise preparation of
magnetic nanoparticles supported imine/
Thiophene nickel (II) complex
(Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2)
FIGURE 1 FT‐IR spectra of Fe3O4
MNPs (A), Fe3O4@SiO2 (B), APTMS‐
Fe3O4@SiO2 (C), imine/Thiophene‐
Fe3O4@SiO2 (D) and Ni(NO3)2−Imine/
Thiophene‐Fe3O4@SiO2 (E)

SHIRI ET AL.
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and efficient synthetic routs toward the preparation of 2, 3‐
dihydroquinazoline‐4(1H)‐one and polyhydroquinoline
derivatives have been focused on using highly active and
reusable catalysts under environmentally benign mediums.
Now, as a part of our research program directed toward the
utility of magnetic nanoparticles,[6,33] herein we wish to report
that Imine/Thiophene‐functionalized silica‐coated magnetic
Fe3O4 nanoparticles is a new support for the immobilization
of nickel (II) complex (Ni(NO3)2). The activity of this magnet-
ically nickel catalyst was investigated in the synthesis of 2,3‐
dihydroquinazoline‐4(1H)‐ones and polyhydroquinolines.
nitrogen conditions. Ultimately, the Imine/Thiophene‐
Fe3O4@SiO2 reacted with Cu(NO3)2.3H2O in refluxing eth-
anol for 6 h to provide the target catalyst (Ni(NO3)2−Imine/
Thiophene‐Fe3O4@SiO2).
As‐prepared catalyst was characterized by several charac-
terization techniques such as FT‐IR, SEM, EDX, VSM,
XRD, TGA, AAS and ICP/OES analysis.
The FT‐IR spectra for the Fe3O4 MNPs (a), Fe3O4@SiO2
(b),
Fe3O4@SiO2
Fe3O4@SiO2 (e) are displayed in Figure 1. The FT‐IR analysis
of the Fe3O4 MNPs exhibits a characteristic peak at 579 cm−1
APTMS‐Fe3O4@SiO2
(c),
Imine/Thiophene‐
(d) and
Ni(NO3)2−Imine/Thiophene‐
,
which is attributed to the Fe‐O stretching vibration. Also the
broad band at around 3400 cm−1 is attributed to bound water
O‐H stretching vibration adsorption. In the curve of
Fe3O4@SiO2 (b), two peaks at 954 and 1084 cm−1 can be
attributed the Si–O–Si stretching vibration of silica shell.
The FT‐IR analysis of the APTMS‐Fe3O4@SiO2 (c) exhibits
that broad bond at 3435 cm−1 is assigned to NH2 group and
two weak peaks at 2921 and 2858 cm−1 are ascribed to the
C‐H stretching vibration of alkyl chain of amine. In the curve
of Imine/Thiophene‐Fe3O4@SiO2 (d), stretching vibrations of
imine bond appeared at 1625 cm−1, while this band shifts to
lower frequency (1612 cm−1) in the Ni(NO3)2−Imine/Thio-
phene‐Fe3O4@SiO2 catalyst. This band shifts to lower fre-
quency confirmed the formation of metal–ligand bonds.
Therefore, it can be concluded that Ni (II) complex was
2 | RESULT AND DISCUSSION
2.1 | Preparation and characterization of
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2
The magnetic nanoparticles supported Imine/Thiophene
nickel (II) complex was successfully fabricated by the con-
cise route outlined in Scheme 1. Silica‐coated magnetic
Fe3O4 nanoparticles (Fe3O4@SiO2) were prepared by chem-
ical co‐precipitation strategy.[35] The Fe3O4@SiO2‐propyl
chloride was prepared by the reaction of Fe3O4@SiO2 with
3‐aminopropyltrimethoxysilane (APTMS) in thermal EtOH/
H2O for 8 h.[5] Next, the imine bond was formed through
the condensation between Fe3O4@SiO2‐propyl amine with
thiophene‐2‐carbaldehyde in refluxing ethanol under
FIGURE 2 SEM image of the
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2

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SHIRI ET AL.
FIGURE 3 EDX spectrum of the
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2
supported successfully on the surface of Imine/Thiophene‐
functionalized silica‐coated magnetic Fe3O4 nanoparticles.
The morphology and size of the nickel nano‐solid was
investigated by Scanning electron microscope (SEM) as
shown in Figure 2 The SEM image of Ni(NO3)2−Imine/Thio-
phene‐Fe3O4@SiO2 shows that the catalyst is formed of
nanometre‐sized particles.
Energy‐dispersive X‐ray spectroscopy (EDX) is an effi-
cient spectra technique to characterize the components of
catalyst. The EDX analysis of Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2 is shown in Figure 3. As shown in Figure 3,
characteristic peaks containing Si, O and Fe are indicative
of the formation of silica coated magnetic support. The
results confirmed the presence of Fe (74.72%), O (7.98%),
Si (2.35%), C (4.03%), N (1.08%), S (0.96%) and Ni
(8.88%) in the sample. Also, another point taken from the
EDX analysis is that there are no any extra peaks related
to any impurity. As
a result of the analysis, the
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 catalyst has been
successfully synthesized.
The magnetic property of the catalyst was investigated
by vibrating sample magnetometer (VSM) at ambient tem-
perature. The curves of magnetization for the Fe3O4 MNPs
(green line) and Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2
(blue line) are depicted in Figure 4. According to the mag-
netization curves, the saturation of the nanoparticles
decreased from 55 emu/g in the initial Fe3O4 sample to
34 emu/g in the final Ni(NO3)2−Imine/Thiophene‐
FIGURE 4 Magnetization curves for Fe3O4 MNPs (green line) and
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 (blue line) at room
temperature
FIGURE 5 The XRD pattern of the Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2

SHIRI ET AL.
5 of 11
Fe3O4@SiO2 catalyst. The decrease of the saturation magne-
tization can be related to the presence of Ni(NO3)2−Imine/
Thiophene on the surface of the Fe3O4@SiO2 nanoparticles
supports.
X‐ray diffraction (XRD) is an efficient spectra technique
to the better reorganization of the major properties of the
magnetite structures. In fact, the formation of magnetite crys-
tal phase in the nanomagnetic catalyst in aggregate powder
form can be as well identified by the X‐ray diffraction
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 is displayed in
Figure 5 the strong characteristic diffraction peaks at
2θ = 35.1o, 41.4o, 50.6o, 63.3o, 67.5o and 74.4o were
observed for Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2
nanoparticles, in which are related to the (220), (311),
(400), (422), (511) and (440) planes. These results are similar
to those of the standard JCPDS 89–3854 exhibiting the iron
oxide characteristic peaks with cubic structure[36] Accord-
ingly, XRD analysis confirmed as well that the
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 have been fabri-
cated successfully without damaging the crystal structure of
Fe3O4 core.
(XRD).
X‐ray
diffraction
(XRD)
spectrum
of
The thermal stability of Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2 was investigated by thermogravimetric analysis
(TGA), and the results is shown in Figure 6. As shown in
Figure 6, the small amount of weight loss below 140°C is
due to desorption of physically adsorbed solvents and surface
hydroxyl groups. Organic groups have been reported to
desorb at temperatures above 220°C. The last stage of degra-
dation in the region of 250‐550°C, probably is due to thermal
decomposition of the complex.
Atomic absorption spectroscopy (AAS) of the catalyst
showed that the amount of nickel loaded on the surface
of
magnetic
Fe3O4
nanoparticles
is
about
15 × 10−5 mmol.g−1. Also, the Ni amount was measured
by atomic absorption spectroscopy (AAS), which the
FIGURE 6 TGA thermogram of the Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2
a
TABLE 1 Optimization of the reaction conditions
Entry
1
Catalyst (mg)
Solvent (Temp.oC)
Peg (100 °C)
Time (min)
Yield (%)a
70
25
25
25
25
25
25
25
20
15
10
20
20
20
20
‐‐
20
20
20
20
20
20
20
20
20
20
20
20
20
20
120
2
DMF (100 °C)
67
3
CH3CN (reflux)
16
4
EtOH (reflux)
56
5
EtOH/H2O (1:1) (80 °C)
H2O (reflux)
45
6
50
7
Solvent‐free (100 °C)
Solvent‐free (100 °C)
Solvent‐free (100 °C)
Solvent‐free (100 °C)
Solvent‐free (r.t)
Solvent‐free (60 °C)
Solvent‐free (90 °C)
Solvent‐free (110 °C)
Solvent‐free (100 °C)
96
8
96
9
90
10
11
12
13
14
15
78
Trace
55
87
95
Trace
aReactions conditions: aldehyde (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1 mmol) and ammonium acetate (1.2 mmol). b Isolated yield.

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SHIRI ET AL.
SCHEME 2 Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2‐catalyzed the synthesis of
polyhydroquinolines
results were very close to ICP‐OES method (15.37×
10−5 mmol.g−1).
absence of solvent at 100°C was considered as the standard-
ized reaction conditions (Table 1, Entry 8).
All together, these analyses are indicative of the success-
ful immobilization of Ni (II) complex onto the Imine/Thio-
phene‐Fe3O4@SiO2 nanoparticles.
Under the standardized conditions, the generality of the
catalytic system was evaluated by the reaction of various
TABLE 2 Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 catalyzed the
synthesis of polyhydroquinolines at 100 °C under solvent‐free
conditions
2.2 | Catalytic studies
After characterization of the catalyst, the catalytic activity of
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 was studied in the
synthesis of polyhydroquinoline and 2,3‐dihydroquinazoline‐
4(1H)‐one derivatives.
Time Yield
Mp (°C)
[ref.]
Entry
Aldehyde
C6H5CHO
Product (min) (%)a
1
2a
2b
2c
20
40
65
25
60
100
55
60
70
50
30
45
96
98
93
92
86
85
91
83
88
87
91
90
214–216[33]
235–237[33]
252–255[33]
184–186[33]
232–236[33]
230–231[33]
182–185[33]
174–177[5]
216–218[5]
230–232[33]
250–251[5]
207–209[5]
2
4‐ClC6H5CHO
4‐OMeC6H5CHO
4‐FC6H5CHO
3
4
2d
2e
2.2.1 | Polyhydroquinolines
5
4‐NO2C6H5CHO
4‐OHC6H5CHO
4‐OEtC6H5CHO
3‐NO2C6H5CHO
3‐OHC6H5CHO
3‐BrC6H5CHO
2‐OMeC6H5CHO
2‐NO2C6H5CHO
Four‐component reaction of benzaldehyde (1a), ethyl
acetoacetate, dimedone and ammonium was chosen as a
simple model substrate to optimize the reaction conditions.
First, the effect of solvent and solvent‐free condition on
the four‐component reaction, catalyzed by 25 mg of
Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2, was investigated
(Table 1, Entries 1–7). A number of solvents such as
PEG, DMF, CH3CN, EtOH, EtOH/H2O and H2O were
tested. In all cases, the reaction afforded the desired product
in poor to moderate yields. As shown in Table 1, the max-
imum yield was observed in the absence of solvent (Table 1
, Entry 7). Next, under solvent‐free conditions, the effect of
catalyst loading on the four‐component reaction was investi-
gated (Table 1, Entries 7–10). As seen in Table 1, the best
results in terms of reaction time and isolated yield were
observed in the presence of 20 mg of Ni(NO3)2−Imine/
Thiophene‐Fe3O4@SiO2 (Table 1, Entry 8). The effect of
temperature on the reaction was then studied. The reaction
was evaluated at different temperatures including r.t, 60,
90 and 110°C (Table 1, Entries 11–14). As seen in
Table 1, higher reaction temperature (110°C) did not
improve the reaction time and product yield, while lower
reaction temperatures (r.t, 60 and 90°C) decreased the prod-
uct yield. Finally, to clarify the role of catalyst in the pro-
cess, the reaction was carried out at in the absence of
catalyst. But, only a trace amount of the product 2a was
observed after 120 min (Table 1, Entry 15). Accordingly,
20 mg of Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 in the
6
2f
7
2 g
2 h
2i
8
9
10
11
12
2j
2 k
2 l
aIsolated yield.
SCHEME
3
Proposed mechanism for the synthesis of
polyhydroquinolines catalyzed by Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2

SHIRI ET AL.
7 of 11
aromatic aldehydes (bearing electron‐donating and electron‐
with drawing groups) with ethyl acetoacetate, dimedone and
ammonium acetate (Scheme 2). The results are listed in
Table 2. As seen in Table 2, a diverse range of the 1,4‐DHP
products were synthesized in high to excellent yields in less
than 100 min. Aromatic aldehydes containing nitro group
on aromatic ring were applicable to this reaction and the
desired products were afforded in lower yields and longer
reaction times (Table 2, Entry 4, 8 and 12).
of anthranilamide with banzaldehyde was chosen as a model
substrate, and the effect of various parameters (such as solvent
type, catalyst and temperature amount) on the model reaction
was studied. First, the effect of solvent on the model reaction
was tested. Among all tested solvents (Table 3, Entries 1–7),
water was found to be the best solvent in terms of the product
yield (Table 3, Entry 7). Next, the effect of catalyst loading (3,
5, 6, 7, 8, and 10) on the model reactionwas evaluated (Table 3,
Entries 8–12). The results in Table 3 showed that the best
results were obtained in 50 min in the presence of 5 mg of cat-
alyst (Table 3, Entry 9). The yield remained unchanged when
the catalyst loading was increased from 5 to 10 mg (Table 3,
Entries 10–12). The reaction at lower reaction temperatures
(r.t, 60, 80 and 90°C) was also tested, but, the obtained results
were disappointing (Table 3, Entries 13–16). Only a trace
amount of the desired product (4a) was obtained in the absence
of the Ni catalyst (Table 3, Entry 17). Ultimately, the reaction
A proposed mechanistic path for the synthesis of
polyhydroquinolines using Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2 as catalyst is depicted in Scheme 3.
2.2.2 | 2,3‐dihydroquinazoline‐4(1H)‐ones
In order to establish the optimum condition for the synthesis of
2,3‐dihydroquinazoline‐4(1H)‐ones, the cyclocondensation
a
TABLE 3 Optimization of the reaction conditions
Entry
1
Catalyst (mg)
Solvent (Temp.oC)
Peg (100 °C)
Time (min)
Yield (%)a
75
7
7
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
55
120
240
2
PhMe (100 °C)
1,4‐dioxane (100 °C)
CH3CN (reflux)
EtOH (reflux)
EtOH/H2O (80 °C)
H2O (reflux)
15
3
7
10
4
7
55
5
7
70
6
7
87
7
7
97
8
3
H2O (reflux)
90
9
5
H2O (reflux)
H2O (reflux)
97
10
11
12
13
14
15
16
17
18
6
97
8
H2O (reflux)
96
10
5
H2O (reflux)
93
H2O (r.t)
5
5
H2O (60 °C)
58
5
H2O (80 °C)
82
5
H2O (90 °C)
92
‐‐
‐‐
H2O (reflux)
Trace
No
Solvent‐free (100 °C)
aReaction conditions: anthranilamide (1.05 mmol) and 4‐chlorobenzaldehyde (1 mmol) in the presence of catalyst and solvent (2 ml). b Isolated yield.
SCHEME 4 Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2 catalyzed the
cyclocondensation of anthranilamide with
aldehydes

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SHIRI ET AL.
TABLE 4 Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 catalyzed the synthesis of 2, 3‐dihydroquinazolin‐4(1H)‐ones in refluxing water
Entry
Aldehyde
C6H5CHO
Product
4a
Time (min)
Yield (%)a
Mp (°C) [ref.]
216–218[33]
198–200[33]
181–184[33]
198–201[33]
222–225[33]
199–200[33]
185–187[33]
173–175[33]
212–214[33]
169–172[33]
203–205[33]
213–215[33]
1
50
40
97
99
92
91
90
94
93
87
91
95
86
88
2
4‐ClC6H5CHO
4‐OMeC6H5CHO
4‐FC6H5CHO
4‐MeC6H5CHO
4‐NO2C6H5CHO
4‐OEtC6H5CHO
3‐BrC6H5CHO
3‐NO2C6H5CHO
2‐OMeC6H5CHO
2‐ClC6H5CHO
4b
3
4c
55
4
4d
45
5
4e
75
6
4f
110
70
7
4 g
4 h
4i
8
100
125
85
9
10
11
12
4j
4 k
4 l
80
3,4‐(OMe)2C6H4CHO
150
aIsolated yield.
did not occur in the absence of catalyst and solvent even after a
long reaction time (240 min) (Table 3, Entry 18).
was obtained in the presence of 5 mg of the catalyst in
refluxing water (Table 3, Entry 9).
After evaluation of the solvent nature, catalytic loading,
the reaction time, and the reaction temperature, the best result
To determine the scope of the protocol, a nice collection
of aromatic aldehydes subjected to react with anthranilamide
under the optimized reaction conditions (Scheme 4). All
results are listed in Table 4. As shown in Table 4, the reac-
tions
proceeded
smoothly
to
give
the
2,3‐
dihydroquinazoline‐4(1H)‐one products in admirable yields
over suitable reaction times. High reaction yield was obtained
when disubstituted aromatic aldehyde vg was targeted as a
substrate (Table 4, Entry 12).
A plausible mechanistic path for the cyclocondensation
of aldehydes with anthranilamide is depicted in Scheme 5.
It seems that enhancing the electrophilicity of the carbonyl
group in aldehyde has occurred using supported metal. Thus,
the intermediate A is formed by the reaction of 2‐
aminobenzamide and activated aldehyde. After dehydration
of intermediate A, the imine intermediate B is produced.
The intramolecular nucleophilic attack of the amide nitrogen
on activated imine group following by a proton transfer leads
to the desired 2,3‐dihydroquinazolinones.
SCHEME 5 Proposed mechanism for the cyclocondensation of
aldehydes with anthranilamide catalyzed by Ni(NO3)2−Imine/
Thiophene‐Fe3O4@SiO2
TABLE 5 Comparison of the activity of various catalysts in the synthesis of products 2b (Entries 1–5) and 4b (Entries 6–10)
Entry
Catalyst
PdCl2
K7[PW11CoO40
Cu‐SPATB/Fe3O4
Condition
THF, reflux
Time (min)
Yield (%)
[ref.]
[25]
1
2
3
4
5
6
7
8
9
10
240
30
87
80
96
95
98
80
97
81
87
99
[37]
[38]
[39]
]
CH3CN, reflux
Peg‐400, 80°C
Solvent‐free, 110°C
Solvent‐free, 100°C
EtOH, reflux
65
[TBA]2[W6O19
]
20
This catalyst
40
This work
[40]
KAl(SO4)2.E12H2O
Glycerosulfonic acid
Silica sulfuric acid
SBNPSA
300
360
180
150
40
[41]
[42]
[43]
Glycerol, 80°C
H2O,80°C
EtOH, reflux
This catalyst
H2O, reflux
This work

SHIRI ET AL.
9 of 11
In order to show the efficiency of present work, the
The loading amount of Ni in the recovered catalyst after
seven times was about 13.47× 10−5 mmol.g−1, which is
determined by ICP/OES analysis.
obtained results for the synthesis of synthesis of products
2b and 4b were compared with the previously reported proce-
dures in the literature (Table 5). As shown in Table 5, this
methodology is superior to some of the reported previously
procedures in terms of product yield, reaction time and reac-
tion conditions.
3 | CONCLUSION
In summary, from obtained experimental results we can con-
clude that the Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 is a
versatile and efficient heterogeneous catalyst for the synthesis
of N‐heterocyclic compounds (2,3‐dihydroquinazoline‐
4(1H)‐ones and polyhydroquinolines). It is noteworthy that
the catalyst can be readily separated and recovered from the
reaction system by a magnet, and reused for at least seven
times without noticeable loss of its activity. Good to excellent
yields, simplicity of operation, high catalytic activity, catalysis
research under water or solvent‐free conditions, easy magnet-
ically separation and reusability of the solid catalyst are nota-
ble advantages of this protocol. As a result of this study, this
catalytic system can act as an efficient strategy for the synthe-
sis of biologically and pharmaceutically active molecules.
2.2.3 | Reusability of the catalyst
The recovery and reusability of catalyst is a valuable advan-
tage in modern catalysis research, in which makes them very
notable from commercial and economical points of view. In
this respect, the reusability of Ni(NO3)2−Imine/Thiophene‐
Fe3O4@SiO2 in the synthesis of products 2b and 4b (as the
model reactions) was investigated. After completion of the
reaction, the catalyst was separated easily and rapidly from
the product by exposure to an external magnet (Figure 7).
The remaining nano‐magnetic catalyst was washed several
times with ethyl acetate and dried to remove residual product,
and subjected to the next run. The magnetically separation
minimizes the loss of catalyst during separation. The recov-
ered catalyst could be reused seven times without any signif-
icant loss in catalytic efficiency (Figure 8).
4 | EXPERIMENTAL
4.1 | Materials
Chemicals were purchased from Fisher and Merck. The
reagents and solvents used in this work were obtained from
Sigma‐Aldrich, Fluka or Merck and used without further
purification. The infrared spectra (IR) of samples were
recorded in KBr disks using a NICOLET impact 410 spec-
1
trometer. HNMR and 13CNMR spectra were recorded with
a Bruker DRX‐400 spectrometer at 400 and 100 MHz respec-
tively. Nanostructures were characterized using a Holland
Philips X, pert X‐ray powder diffraction (XRD) diffractome-
ter (Co Kα, radiation = 0.154056 nm), at a scanning speed of
2° min−1 from 10° to 80°. Scanning electron microscope
(SEM) was performed on a FEI Quanta 200 SEM operated
at a 20 kV accelerating voltage. The thermogravimetric anal-
ysis (TGA) curves are recorded using a PL‐STA 1500 device
manufactured by Thermal Sciences. The magnetic measure-
ments were carried out in a vibrating sample magnetometer
(VSM, BHV‐55, Riken, Japan) at room temperature.
FIGURE 7 (A) reaction mixture and (B) recovery of catalyst from
the reaction mixture using an external magnet
4.2 | Preparation of the magnetic Fe3O4‐
nanoparticles
The mixture of FeCl3.6H2O (5.838 g, 0.0216 mol) and
FeCl2.4H2O (2.147 g, 0.0108 mol) were dissolved in
100 ml of deionized water in a three‐necked bottom
(250 mL) under N2 atmosphere. After that, under rapid
mechanical stirring, 10 ml of NH3 was added into the solu-
tion within 30 min with vigorous mechanical stirring. After
FIGURE 8 Reusability of Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2
in the synthesis of products2b and 4b

10 of 11
SHIRI ET AL.
being rapidly stirred for 30 min, the resultant black dispersion
was heated to 80°C for 30 min. The black precipitate formed
was isolated by magnetic decantation, washed with double‐
distilled water until neutrality, and further washed twice with
ethanol and dried at room temperature.[29,44]
absolute ethanol, and dried under vacuum at room tempera-
ture (Scheme 1).
4.7 | General procedure for the synthesis of
polyhydroquinolines
A mixture of aldehyde (1 mmol), dimedon (1 mmol),
ethylacetoacetate (1 mmol), ammonium acetate (1.2 mmol)
and Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2 (20 mg) was
stirred at 100°C under solvent‐free conditions. Reaction
progress was monitored by TLC (acetone: n‐hexane, 3:7).
After completion of the reaction, the catalyst was separated
using an external magnet and washed with ethyl acetate.
Then, the solvent was evaporated and all products were
recrystallized from ethanol. The pure polyhydroquinoline
derivatives were obtained in excellent yields (83–98%).
4.3 | Preparation of the Fe3O4@SiO2:
Then the obtained Fe3O4 MNPs (2 g) were dispersed in 20 ml
of water by sonication for 30 min, and then 2‐propanol
(200 ml) was added to the reaction mixture. The reaction
mixture was stirred using a magnetic stirrer at room temper-
ature. Under continuous stir‐ring, PEG (5.36 g), water
(20 ml), ammonia solution (10 ml, 28 wt.%) and 2 ml of
tetraethyl orthosilicate (TEOS) were respectively added into
the suspension, and continuously reacted for 38 h under stir-
ring at room temperature. Then the products (Fe3O4@SiO2)
were isolated with an external magnet and washed two times
with ethanol and distilled water.[35]
4.8 | General procedure for the synthesis of
2,3‐dihydroquinazolin‐4(1H)‐ones:
A mixture of anthranilamide (1.05 mmol, 142 mg), aldehyde
(1 mmol) and Ni(NO3)2−Imine/Thiophene‐Fe3O4@SiO2
(5 mg) in water (2 ml) was stirred at reflux temperature.
Reaction progress was monitored by TLC (acetone: n‐hex-
ane, 2:8). After time specified in Table 4, reaction mass
was allowed to cool down to room temperature. CH2Cl2
(3 × 5 ml) was added to reaction mixture and the catalyst
was separated by an external magnet. CH2Cl2 was evaporated
under reduced pressure to afford the crude products. The
obtained crude products were further recrystallized from eth-
anol to get the pure 2,3‐dihydroquinazolin‐4(1H)‐ones (86–
99%).
4.4 | Preparation of APTMS‐Fe3O4@SiO2
The obtained Fe3O4@SiO2 nanoparticles (1.5 g) was dis-
persed in 250 ml ethanol/water (volume ratio, 1:1) by sonica-
tion for 30 min, and then APTMS (2.5 ml) was added to the
mixture reaction. The reaction mixture was stirred using
mechanical stirring under N2 atmosphere at 40°C for 8 h.
then, the nanoparticles was re‐dispersed in ethanol by sonica-
tion for 5 times and separated through magnetic decantation.
The nanoparticles product (APTMS‐Fe3O4@SiO2) was dried
at room temperature.[2]
All the products reported here are known compounds and
their spectroscopic data are reported in the literature.
4.5 | Preparation of imine/Thiophene‐
Fe3O4@SiO2
The APTMS‐Fe3O4@SiO2 (3 g) were dispersed in EtOH
(60 ml) by ultrasonic bath for 10 min. Thiophene‐2‐
carbaldehyde (6 mmol, 672 g) was added and stirred at reflux
temperature for 12 h under N2 atmosphere. Then, the pre-
pared functionalized magnetic nanoparticles were separated
by magnetic decantation and washed five times with ethanol
to remove the unattached substrates. The resulting product
was dried at room temperature.
ACKNOWLEDGEMENTS
This work was supported by the research facilities of Ilam
University, Ilam, Iran.
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How to cite this article: Shiri L, Heidari L, Kazemi
M. Magnetic Fe3O4 nanoparticles supported imine/
Thiophene‐nickel (II) complex: A new and highly
active heterogeneous catalyst for the synthesis of
polyhydroquinolines and 2, 3‐dihydroquinazoline‐
4(1H)‐ones. Appl Organometal Chem. 2017;e3943.
https://doi.org/10.1002/aoc.3943
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