Synthesis and characterization of Fe3O4@THAM-SO3H as a highly reusable nanocatalyst and its application for the synthesis of dihydropyrano[2,3-c]pyrazole derivatives

Article abstract of DOI:10.1002/aoc.5472

In this work, a new, green and beneficial nanomagnetic catalyst was easily fabricated using sulfuric acid as an acidic group on Fe₃O₄ nanoparticles coated with tris (hydroxymethyl) aminomethane (THAM). The synthesized catalyst was characterized by FT-IR, TGA/DTG, XRD, TEM, EDS, VSM, and SEM analyses. Next, its catalytic activity was studied for the synthesis of dihydropyrano[2,3-c]pyrazole derivatives. This catalyst has advantages such as high catalytic activity, non-toxicity, easy separation from the reaction mixture using an external magnet and reuses for several times without significantly reducing in its catalytic activity.

Full text of DOI:10.1002/aoc.5472

Received: 20 September 2019
DOI: 10.1002/aoc.5472
Revised: 5 December 2019
Accepted: 8 December 2019
F U L L P A P E R
Synthesis and characterization of Fe3O4@THAM-SO3H as a
highly reusable nanocatalyst and its application for the
synthesis of dihydropyrano[2,3-c]pyrazole derivatives
Homayoun Faroughi Niya | Nourallah Hazeri
| Malek Taher Maghsoodlou
Department of Chemistry, Faculty of
In this work, a new, green and beneficial nanomagnetic catalyst was easily
fabricated using sulfuric acid as an acidic group on Fe3O4 nanoparticles coated
with tris (hydroxymethyl) aminomethane (THAM). The synthesized catalyst
was characterized by FT-IR, TGA/DTG, XRD, TEM, EDS, VSM, and SEM
analyses. Next, its catalytic activity was studied for the synthesis of
dihydropyrano[2,3-c]pyrazole derivatives. This catalyst has advantages such as
high catalytic activity, non-toxicity, easy separation from the reaction mixture
using an external magnet and reuses for several times without significantly
reducing in its catalytic activity.
Science, University of Sistan and
Baluchestan, P.O. Box 98135-674,
Zahedan, Iran
Correspondence
Nourallah Hazeri, Department of
Chemistry, Faculty of Science, University
of Sistan and Baluchestan, P.O. Box
98135-674, Zahedan, Iran.
Email: nhazeri@chem.usb.ac.ir;
n_hazeri@yahoo.com
Funding information
University of Sistan and Baluchestan
K E Y W O R D S
Fe3O4@THAM-SO3H, heterogeneous nanocatalyst, magnetite nanoparticles, multicomponent
reaction
1 | INTRODUCTION
without significantly reducing in its catalytic
activity.[16–20]
In recent years, magnetic nanoparticles (MNPs)
(especially superparamagnetic Fe3O4 nanoparticles) are
used in various applications in pharmaceutical industries
and green chemistry such as drug delivery vehicles,[1,2]
sensors,[3] and catalysts.[4,5] MNPs received considerable
attention due to their superior characteristics such as
high surface energies, high surface to volume ratios, easy
recoverability, enhanced dispersion, high catalytic
performance, and reusing without loss of their catalytic
activity.[6–12] One of the most essential abilities of MNPs
in organic chemistry is their catalyst role in
multicomponent reactions (MCRs). The use of heteroge-
neous magnetic nanocatalyst has been widely reported.
These nanocatalysts have small size and large external
surface areas that allow great accessibility of substrates to
the surface-bound active catalytic sites.[13–15] Also, their
applications are increased due to their superior character-
istics such as easily removable from the reaction mixture
using an external magnet and reuse for several times
As a review of previous studies, many methods have
been reported for sulfuric acid coupling as an
acidic group on magnetic nanoparticles. Among them,
Fe3O4@APTES@isatin-SO3H,[21]
CoFe2O4@SiO2-
SO3H,[22] Fe3O4@BNPs@SiO2–SO3H,[23] Fe3O4@zeolite-
SO3H,[24] Fe3-xTixO4-SO3H[25] and Fe3O4@GO-naphtha-
lene-SO3H[26] are examples of catalysts.
Pyranopyrazoles and their derivatives such as
dihydropyrano[2,3-c]pyrazole
derivatives
are
an
important class of heterocyclic compounds which have
significant biological activities, such as anticancer,[27]
vasodilatory[28] and bactericidal[29] activities. These mole-
cules are also used as biodegradable agrochemicals and
pharmaceutical
ingredients.[30]
Furthermore,
dihydropyrano[2,3-c]pyrazole derivatives have attracted
attention as molluscicidal agents[31,32] and potential
insecticidal.[33]
In continue the development of synthesis of MNPs as
a green catalyst for the production of pharmaceutical
Appl Organometal Chem. 2020;e5472.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5472

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FAROUGHI NIYA ET AL.
compounds in one pot synthesis, we wish to
propose a nanomagnetic catalyst using sulfuric acid as an
acidic group on Fe3O4 nanoparticles coated with THAM.
Then, the synthesized nanocatalyst was used as a
recyclable catalyst sorbents for one-pot synthesis
of dihydropyrano[2,3-c]pyrazole derivatives from reaction
between benzaldehyde (1), malononitrile (2) and
5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (6) or
hydrazine hydrate (3) and acetoacetate (4) (Scheme 1).
2.3 | Synthesis of magnetite
nanoparticles coated by tris
(hydroxymethyl) aminomethane
THAM-capped Fe3O4 were prepared according to previ-
ous reports.[34] The synthesized Fe3O4 (1.0 g) and 50 ml
of ethanol were ultrasonically dispersed for 30 min. Then,
to this suspension, 2.0 g of tris (hydroxymethyl)
aminomethane (THAM) was added. The reaction mixture
was stirred for 24 hr at 100 ꢀC under N2 atmosphere.
Finally, The resulting nanoparticles (Fe3O4@THAM)
were separated by an external magnet and washed several
times with water to remove unreacted material and dried
at 60 ꢀC.
2 | EXPERIMENTAL
2.1 | General
Melting points and FT-IR spectra of compounds were
measured with an Electrothermal 9100 apparatus. The
1H NMR spectra were obtained on BRUKER DRX
300 and 400 MHz, using DMSO as a solvent. Ferrous
chloride tetrahydrate (FeCl2Á4H2O) and ferric chloride
hexahydrate (FeCl3Á6H2O) were obtained from Aldrich.
Other reagents and solvents were obtained from Aldrich
and Merck and were used without further purification.
2.4 | Synthesis of Fe3O4@THAM-SO3H
An amount of 1.0 g of the prepared magnetite Fe3O4@-
THAM nanoparticles was dispersed in 50 ml chloroform
by ultrasonic bath for 20 min. Then, subsequently,
chlorosulfonic acid (1.5 ml) was added dropwise and the
resulting reaction mixture was stirred for 4 hr at room
temperature under N2 atmosphere. The resulting
nanoparticles (Fe3O4@THAM-SO3H) were separated by
an external magnet and washed several times with etha-
nol to remove the remaining acid and dried at 60 ꢀC.
2.2 | Synthesis of the magnetic Fe3O4
nanoparticles
Fe3O4 nanoparticles (NPs) have been synthesized by
chemical coprecipitation method. Briefly, FeCl2Á4H2O
(0.994 g, 5.0 mmol) and FeCl3Á6H2O (2.703 g, 10.0 mmol)
were dissolved in 100 ml deionized water under nitrogen
flow. Thereafter, 25% ammonia solution was added
dropwise to the solution under vigorous stirring at
1000 rpm. After reaching the pH of 11, the mixture was
stirred vigorously for 1 hr at room temperature. Finally,
the nanoparticles obtained were separated and washed
several times with ethanol and diethyl ether and dried for
2 hr at 60 ꢀC in an oven.
2.5 | General procedure for four-
component synthesis of
dihydropyrano[2,3-c]pyrazole derivatives
Initially, the reactant ethyl acetoacetate (1.0 mmol) and
hydrazine hydrate (1.0 mmol) were taken at room tem-
perature until 3-methyl-2-pyrazoline-5-one was precipi-
tated as white solid. Then, malononitrile (1.0 mmol),
aromatic aldehyde (1.0 mmol) and Fe3O4@THAM-SO3H
(10 mg) in ethanol/water (1:1) was added to the reaction
ꢀ
mixture at 100 C and stirred for the appropriate time.
SCHEME 1 Fe3O4@THAM-SO3H catalyzed
the one-pot synthesis of dihydropyrano[2,3-c]
pyrazoles derivatives

SYNTHESIS, CHARACTERIZATION AND APPLICATION OF FE3O4@THAM-SO3H
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1
After the completion of the reaction which was
monitored by TLC, the product was dissolved in hot
ethanol and the catalyst separated by an external magnet,
and the resulting solution was cooled to room tempera-
ture, the desired product precipitated and crystalized,
then it was filtered.
752, 853 (C-H). H-NMR (300 MHz, DMSO) δ = 1.83 (s,
3H, CH3), 3.66 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 4.94 (s,
1H, CH), 6.54 (d, J = 3 Hz, 1H, Ar-H), 6.79 (dd,
J1 = 8.7 Hz, J2 = 3 Hz, 1H, Ar-H), 6.84 (s, 2H, NH2), 6.95
(d, J = 9 Hz, 1H, Ar-H), 12.03 (s, 1H, N-H).
2.6 | General procedure for three-
component synthesis of
dihydropyrano[2,3-c]pyrazole derivatives
2.7.4 | 6-amino-1,4-dihydro-3-methyl-
4-(4-bromophenyl)pyrano[2,3-c]pyrazole-
5-carbonitrile (5e)
A mixture of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-
3-one (1.0 mmol), malononitrile (1.0 mmol), aldehydes
(1.0 mmol) and Fe3O4@THAM-SO3H (10 mg) in
ethanol/water (1:1) was stirred at 100 ꢀC for the appropri-
ate time. After the completion of the reaction which was
monitored by TLC, the product was dissolved in hot
ethanol and the catalyst separated by an external magnet,
and the resulting solution was cooled to room tempera-
ture, the desired product precipitated and crystalized,
then it was filtered. The spectra of selected compounds
have been reported in supporting information.
1H-NMR (300 MHz, DMSO) δ = 1.80 (s, 3H, CH3), 4.63
(s, 1H, CH), 6.96 (s, 2H, NH2), 7.15 (d, J = 8 Hz, 2H, Ar-
H), 7.54 (d, J = 8 Hz, 2H, Ar-H), 12.17 (s, 1H, N-H).
2.7.5 | 6-Amino-3-methyl-1,4-diphenyl-
1,4-dihydropyrano[2,3,c]pyrazole-
5-carbonitrile (7a)
FT-IR (KBr, νmax, cm−1): 3471 (NH2), 3324 (NH), 3063
(C-Haromatic), 2919 (C-Haliphatic), 2198 (CN), 1592, 1516
1
(C=C), 685, 753 (C-H). H-NMR (300 MHz, DMSO): (δ,
2.7 | Selected spectra for seven known
products are given below
ppm): 1.80 (s, 3H, CH3), 4.70 (s, 1H, CH), 7.23 (s, 2H,
NH2), 7.26–7.40 (m, 6H, Ar-H), 7.51 (t, J = 8 Hz, 2H, Ar-
H), 7.81 (d, J = 9 Hz, 2H, Ar-H).
2.7.1 | 6-Amino-1,4-dihydro-3-methyl-
4-(2-chlorophenyl)pyrano[2,3-c]pyrazole-
5-carbonitrile (5b)
2.7.6 | 6-Amino-1,4-dihydro-3-methyl-
4-(2,4-dichlorophenyl)-
1-phenylpyrano[2,3-c]pyrazole-
5-carbonitrile (7b)
FT-IR (KBr, νmax, cm−1): 3391 (NH2), 3357 (NH2), 3314
(NH), 2925(C-Haliphatic), 2190 (CN), 1654 (C=N), 1272 (C-
1
O). H NMR (300 MHz, DMSO) δ = 1.82 (s, 3H, CH3),
5.12 (s, 1H, C-H), 7.00 (s, 2H, NH2), 7.22–7.66 (m, 4H,
Ar-H),12.18 (s, 1H, NH).
1H NMR (400 MHz, DMSO): δ = 1.81 (s, 3H, CH3), 4.74
(s, 1H, CH), 7.31–7.44 (m, 5H, NH2 and ArH), 7.48–7.52
(m, 2H, ArH), 7.62 (s, 1H, ArH), 7.78 (d, J = 8 Hz, 2H,
ArH).
2.7.2 | 6-Amino-1,4-dihydro-3-methyl-
4-(2-nitrophenyl)pyrano[2,3-c]pyrazole-
5-carbonitrile (5c)
2.7.7 | 6-amino-1,4-dihydro-3-methyl-
4-(4-chlorophenyl)-1-phenylpyrano[2,3-c]
pyrazole-5-carbonitrile (7c)
FT-IR (KBr, νmax, cm−1): 3414 (NH2), 3376 (NH2), 3315
(NH), 2186 (CN), 1158 (C-O). 1H NMR (300 MHz, DMSO)
δ = 1.79 (s, 3H, CH3), 5.11 (s, 1H, CH), 7.05 (s, 2H, NH2),
7.33–7.92 (m, 4H, Ar-H), 12.22 (s, 1H, NH).
1H NMR (400 MHz, DMSO): δ = 1.79 (s, 3H, CH3), 5.16
(s, 1H, CH), 7.28–7.79 (m, 9H, ArH), 7.81 (s, 2H, NH2).
3 | RESULTS AND DISCUSSION
2.7.3 | 6-amino-1,4-dihydro-3-methyl-
4-(3,4-dimethoxyphenyl)pyrano[2,3-c]
pyrazole-5-carbonitrile (5d)
3.1 | Synthesis and characterization of
catalyst
FT-IR (KBr, νmax, cm−1): 3456 (NH2), 3346 (NH2), 3229
In this work, we prepared
a new nanocatalyst
(NH), 2971(C-Haliphatic), 2209 (CN), 1568, 1642 (C=C),
(Fe3O4@THAM-SO3H) by following the method shown

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FAROUGHI NIYA ET AL.
in Scheme 2. In the first step, The Fe3O4 MNPs were
prepared by chemical coprecipitation method. Then,
chlorosulfonic acid was coated on the surface of
magnetite nanoparticles using tris (hydroxymethyl)
aminomethane. The synthesized nanocatalyst was
characterized using several techniques, including Fourier
transform infrared (FT-IR), X-ray diffraction (XRD),
thermogravimetric (TGA), differential thermal analysis
(DTA), vibrating sample magnetometer (VSM), field
emission scanning electron microscopy (FE-SEM), X-ray
spectroscopy (EDS), and TEM analyses.
The determination of the size and morphology of the
Fe3O4@THAM-SO3H was performed by FESEM. As
shown in Figure 1, The particles of uncoated Fe3O4 and
Fe3O4@THAM-SO3H are uniform in both shape and size.
The FESEM image of the nanocatalyst (Fe3O4@THAM-
SO3H) showed the spherical-shaped nanoparticles and an
average size of approximately 14 nm. The size histogram
of Fe3O4 (a) and Fe3O4@THAM-SO3H (b) was con-
structed by measuring 200 particles that appear in the
FESEM image (Figure 2).
The EDS spectrum of Fe3O4@THAM-SO3H exhibited
in Figure 3. This spectrum showed the presence of oxy-
gen (O, 25%), sulfur (S, 2.2%), nitrogen (N, 1.2%), carbon
(C, 17.3%) and iron (Fe, 54.3%) elements. This spectrum
is proof for the fact that the organic layer (THAM-SO3H)
was immobilized onto the Fe3O4 nanoparticles.
TEM images, which is presented in Figure 4, clearly
demonstrates that the nanocatalyst was composed of two
parts, brighter and darker parts (core-shell structure).
The brighter parts of the image are likely related to the
organic layer anchored to the surface of the Fe3O4 NPs
and the darker parts correspond to magnetic
nanoparticles. Also, the TEM image of Fe3O4@THAM-
SO3H exhibits that the morphology of nanoparticles is
almost spherical with a narrow size distribution of about
11 nm (Figure 5), which confirmed the achieved
SEM data.
The characterization of Fe3O4@THAM-SO3H was
confirmed by FT-IR spectrum (Figure 6) which showed
spectra of Fe3O4 (a) and Fe3O4@THAM-SO3H (b). In
Figure 6a can be seen the Fe-O stretching vibration of
Fe3O4 at 550–650 cm−1. Also, two peaks at 1618 cm−1
and 3374 cm−1 are attributed to bending vibration and
stretching vibration of the OH functional groups on the
surface of Fe3O4, respectively. The spectrum of
Fe3O4@THAM-SO3H (Figure 6b) shows some bands in
1000–1250 cm−1 which are attributed to the absorption S-
O and S=O stretching bands of -SO3H moiety on
Fe3O4@THAM-SO3H surface. In addition, the peak at
3405 cm−1 in the spectrum of Fe3O4@THAM-SO3H was
probably attributed to the -SO2-OH groups, which is over-
lapped by the Fe–OH stretching vibration.[21]
The thermal stability of Fe3O4@THAM-SO3H
nanoparticles was studied byꢀTG/DTG analysis in the
decomposition area of 0–600 C with a heating rate of
ꢀ
10 C per minute under nitrogen atmosphere (Figure 7).
As can be seen, Fe3O4@THAM-SO3H nanoparticles dis-
played four weight-loss steps. The initial weight loss
ꢀ
(4.82%) from room temperature to 180 C is related to
loss of physically adsorbed solvent and the surface
hydroxyl groups. The second weight loss (5.09%) between
180 and 330 ꢀC is due to thermal decomposition of acidic
functional groups (SO3H) of the nanocatalyst. The other
organic moiety grafted on the Fe3O4 NPs decomposed at
elevated temperatures (weight loss 11.41%). The total
weight loss was computed to be 16.5%. In accordance
with this mass loss, it was computed that the amount of
0.85 mmol of the organic layer (THAM-SO3H) was loaded
on 1 g of Fe3O4 nanoparticles. Furthermore, the DTG
curve shows that the decomposition of the organic struc-
ꢀ
ture mainly happened at 250 C. So, the Fe3O4@THAM-
SO3H is stable below this temperature.
The XRD pattern of Fe3O4@THAM-SO3H and Fe3O4
was investigated in the domain of 5–80 degrees
(Figure 8). The powder XRD pattern of the Fe3O4
SCHEME 2 Preparation of
Fe3O4@THAM-SO3H

SYNTHESIS, CHARACTERIZATION AND APPLICATION OF FE3O4@THAM-SO3H
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FIGURE 1 SEM images of Fe3O4 (a) and
Fe3O4@THAM-SO3H (b)
FIGURE 2 The size histogram of Fe3O4 (a) and Fe3O4@THAM-SO3 (b)
The magnetic properties of Fe3O4 NPs and
Fe3O4@THAM-SO3H were analyzed via VSM at room
temperature (Figure 9). The M(H) hysteresis loop was
completely reversible. Hence, these results indicate that
nanocatalyst possesses sufficient superparamagnetism.
The magnetic saturation (Ms) values of Fe3O4 NPs and
Fe3O4@THAM-SO3H are 116.6 and 42.3 emu g − 1,
respectively. The decrease of MS for the synthesized
nanocatalyst (Fe3O4@THAM-SO3H) is due to the non-
magnetic nature of the organic layer anchored to the sur-
face of the Fe3O4 NPs.
FIGURE 3 EDS spectrum of Fe3O4@THAM-SO3H
3.2 | Catalytic application of
Fe3O4@THAM-SO3H
(Figure 8a) exhibited diffraction peaks at 2θ = 30.03ꢀ,
35.68ꢀ, 43.36ꢀ, 53.85ꢀ, 57.35ꢀ, 62.79ꢀ and 74.43ꢀ, which
are associated with corresponding indices of (2 0 2), (3 1
1), (4 0 0), (4 2 2), (5 1 1), (4 4 0) and (6 6 0), respectively.
In the XRD pattern of Fe3O4@THAM-SO3H (Figure 8b),
an additional broad peak at region lower than 20ꢀ is seen
which can be attributed to the existence of amorphous
organic layer (THAM-SO3H) that was immobilized onto
the Fe3O4 nanoparticles.
In order to evaluate the catalytic activity of the
Fe3O4@THAM-SO3H nanoparticles, they were used in
the synthesis of dihydropyrano[2,3-c]pyrazole derivatives
(Scheme 1). To find the optimal reaction conditions, the
four-component
reaction
of
benzaldehyde
(1),
malononitrile (2), hydrazine hydrate (3) and acetoacetate
(4) was chosen as a model reaction. Initially, the influ-
ence of a variety of solvents was investigated using

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FAROUGHI NIYA ET AL.
FIGURE 4 TEM images of
Fe3O4@THAM-SO3H
FIGURE 5 The size histogram of
Fe3O4@THAM-SO3H
FIGURE 6 FT-IR spectra of Fe3O4
(a) and Fe3O4@THAM-SO3H (b)
various solvents such as ethanol, water, or mixture of
ethanol:water (1:1). All of the results are registered in
Table 1. Among the studied solvents, mixture of ethanol:
water (1:1) exhibited the most potent effect on the model
reaction (Table 1, entry 2).
of temperature was studied. Based on our experimental
results, ꢀthe best result is obtained in ethanol:water (1:1)
at 100 C in the presence of 10 mg of Fe3O4@THAM-
SO3H for 10 min. In these conditions, the desired product
was obtained at 80% yields (Table 2, entry 9).
In the next step, the model reaction was performed
with various amounts of nanoparticles (5, 7.5, 10, 15 mg).
All of the results are registered in Table 2. The best result
was obtained in the presence of 10 mg of Fe3O4@THAM-
SO3H as a catalyst which confirmed the catalytic activity
of Fe3O4@THAM-SO3H nanoparticles. Finally, the effect
After optimizing the reaction conditions, of benzalde-
hyde (1), malononitrile (2), hydrazine hydrate (3) and
acetoacetate (4) under optimized conditions for prepara-
tion of dihydropyrano[2,3-c]pyrazole derivatives was
investigated. Interestingly, a variety of aromatic alde-
hydes including, para, meta, ortho-substituted were used

SYNTHESIS, CHARACTERIZATION AND APPLICATION OF FE3O4@THAM-SO3H
7 of 11
FIGURE 7 TGA and DTG
curves of Fe3O4@THAM-SO3H
FIGURE 8 XRD pattern of Fe3O4 (a) and
Fe3O4@THAM-SO3H (b)
and corresponding products were synthesized in excellent
yields at short reaction times (Table 3).
A
proposed mechanism for the synthesis of
dihydropyrano[2,3-c]pyrazoles is provided in Scheme 3.
In the first step, the electrophilicity of the carbonyl group
of aldehyde (1) was increased by the proton from
Fe3O4@THAM-SO3H. Next, the Knoevenagel condensa-
tion of malononitrile (2) with activated aldehyde
generates 2-benzylidenemalononitrile intermediate (a).
In the second step, Michael addition of 5-methyl-2-phe-
nyl-2,4-dihydro-3H-pyrazol-3-one (6) or pyrazolone (b)
(from the reaction between ethyl acetoacetate (4) and
hydrazine hydrate (3)) to 2-benzylidene malononitrile
FIGURE 9 VSM spectra of Fe3O4 (a) and Fe3O4@THAM-
intermediate
(a),
followed
by
continuous
SO3H (b)
intramolecular cyclization happen to give the intermedi-
ate (d). Finally, tautomerization affords the
corresponding product.
TABLE 1 Optimization of solvent at 60 ꢀC
Entry
Solvent
EtOH
Time (min)
Yield (%)
3.3 | Catalyst recovery and reuse
1
2
3
50
30
35
37
67
66
H2O:EtOH (1:1)
H2O
The recyclability and stability of the catalyst was
checked using the three-component reaction of

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FAROUGHI NIYA ET AL.
TABLE 2 Effect of the catalyst amount and temperature on the model reaction
Entry
Catalyst (gr)
Temperature (ꢀC)
Time (min)
Yield (%)
1
No catalyst
60
60
40
40
40
30
30
30
20
10
10
56
50
53
67
55
70
68
80
75
2
0.005
3
0.0075
0.01
60
4
60
5
0.015
0.01
60
7
70
8
0.01
90
9
0.01
100
110
10
0.01
4-chlorobenzaldehyde, malononitrile, and 5-methyl-
2-phenyl-2,4-dihydro-3H-pyrazol-3-one, using the
recycled catalyst under the optimized conditions. After
completion of the reaction, the product was dissolved
in hot ethanol (30 ml) and the catalyst separated by an
external magnet and washed with ethanol for three
times ꢀto remove any organic moieties present and dried
at 60 C. The catalyst was used directly in the next run.
As shown in Figure 10, the catalyst could be reused
eight times with no significant reduction in its activi-
ties. This small decrease can be attributed to the loss of
catalyst after every recycling.
TABLE 3 Synthesis of dihydropyrano[2,3-c]pyrazole derivatives in the presence of Fe3O4@THAM-SO3H (0.01 g) in water/ethanol (1:1)
at 100 ꢀC
Entry
Product
Time (min)
Yield (%)
M.p (ꢀC)
M.p (ꢀC) [Lit.]Ref.
1
10
80
244–246
243–245[35]
5a
2
15
75
143–145
145–147[35]
5b
3
25
69
226–228
227–228[36]
(Continues)

SYNTHESIS, CHARACTERIZATION AND APPLICATION OF FE3O4@THAM-SO3H
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TABLE 3 (Continued)
Entry
Product
Time (min)
Yield (%)
M.p (ꢀC)
M.p (ꢀC) [Lit.]Ref.
5c
4
10
81
190–193
189–193[35]
5d
5
5
85
180–181
178–180[35]
5e
6
20
82
165–168
167–169[35]
7a
7
10
88
182–184
181–183[35]
7b
(Continues)

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FAROUGHI NIYA ET AL.
TABLE 3 (Continued)
Entry
Product
Time (min)
Yield (%)
M.p (ꢀC)
M.p (ꢀC) [Lit.]Ref.
8
5
98
169–171
170–172[35]
7c
SCHEME 3 Proposed mechanism for the synthesis of dihydropyrano[2,3-c]pyrazoles
FIGURE 10 Reusability of the
nanocatalyst in the synthesis of 6-amino-
1,4-dihydro-3-methyl-4-(4-chlorophenyl)-
1-phenylpyrano[2,3-c]pyrazole-5-carbonitrile

SYNTHESIS, CHARACTERIZATION AND APPLICATION OF FE3O4@THAM-SO3H
11 of 11
[14] V. Moodley, S. Maddila, S. B. Jonnalagadda, W. E. van Zyl,
New J. Chem. 2017, 41, 6455.
4 | CONCLUSIONS
[15] S. Safaei, I. Mohammadpoor-Baltork, A. R. Khosropour,
M. Moghadam, S. Tangestaninejad, V. Mirkhani, Catal. Sci.
Technol. 2013, 3, 2717.
[16] H. R. Shaterian, M. Mohammadnia, Res. Chem. Intermed.
2013, 39, 4221.
In this study, The Fe3O4 nanoparticles (NPs) was
synthesized easily by chemical coprecipitation method at
room temperature. The synthesis of Fe3O4 NPs at room
temperature has some advantage such as better magnetic
properties and avoids Fe3O4 to γ-Fe2O3 conversion. Then,
[17] A. R. Moosavi-Zare, M. A. Zolfigol, M. Zarei, A. Zare,
V. Khakyzadeh, J. Mol. Liq. 2015, 211, 373.
Fe3O4@THAM-SO3H as
a
magnetically retrievable
[18] H. R. Shaterian, F. Mordi, Res. Chem. Intermed. 2015, 41, 291.
[19] F. Khorami, H. R. Shaterian, Res. Chem. Intermed. 2015, 41,
3171.
[20] H. R. Shaterian, A. Hosseinian, Res. Chem. Intermed. 2014, 40,
3011.
nanocatalyst was synthesized and characterized by
several analyses including FT-IR, XRD, SEM, EDS, TEM,
VSM, and TG/DTG. The synthesized nanocatalyst was
successfully
employed
in
the
synthesis
of
dihydropyrano[2,3-c]pyrazole derivatives. This heteroge-
neous nanocatalyst has the following advantages: easy
product separation and purification, reusability for eight
reactions cycles without any significant decrease in cata-
lytic activity, eco-friendly nature that make it sustainable,
attractive and economic in agreement with some green
chemistry protocols.
[21] S. Sajjadifar, Z. Gheisarzadeh, Appl. Organomet. Chem. 2019,
33, e4602.
[22] S. Mandal, S. Hazra, S. Sarkar, C. Bodhak, A. Pramanik, Appl.
Organomet. Chem. 2019, 33, e4702.
[23] M. G. Kermanshahi, K. Bahrami, RSC Adv. 2019, 9, 36103.
[24] M. Kalhor, Z. Zarnegar, F. Janghorban, S. A. Mirshokraei, Res.
Chem. Intermed. 2019, 1.
[25] D. Azarifar, Y. Abbasi, M. Jaymand, M. A. Zolfigol,
M. Ghaemi, O. Badalkhani, J. Organomet. Chem. 2019.
[26] M. Khaleghi-Abbasabadi, D. Azarifar, Res. Chem. Intermed.
2019, 45, 2095.
ACKNOWLEDGEMENTS
The authors gratefully appreciate the financial support
from the Research Council of University of Sistan and
Baluchestan.
[27] M. R. Nadia, Y. K. Nahed, A. A. Fahmyb, A. A. F. El-Sayeda,
Pharma Chem. 2010, 2, 400.
[28] V. K. Ahluwalia, A. Dahiya, V. Garg, Indian J. Chem. 1997,
36B, 88.
[29] M. N. Nasr, M. M. Gineinah, Arch. Pharm. Med. Chem. 2002,
335, 289.
[30] H. Junek, H. Aigner, Chem. Ber. 1973, 106, 914.
[31] F. M. Abdelrazek, P. Metz, N. H. Metwally, S. F. El-Mahrouky,
Arch. Pharm. 2006, 339, 456.
ORCID
Nourallah Hazeri https://orcid.org/0000-0002-0560-
7245
Malek Taher Maghsoodlou https://orcid.org/0000-0002-
4454-8049
[32] A. Siddekha, A. Nizam, M. A. Pasha, Spectrochim. Acta B.
2011, 81, 431.
[33] E. S. El-Tamany, F. A. El-Shahed, B. H. Mohamed, J. Serb.
Chem. Soc. 1999, 64, 9.
[34] S. M. El-Sigeny, M. F. Abou Taleb, Life Sci. J. 2015, 12, 161.
[35] H. Pejman, N. Hazeri, M. Fatahpour, H. Faroughi Niya, Rev.
Roum. Chim. 2019, 64, 241.
REFERENCES
[1] S. Laurent, D. Forge, M. Port, A. Roch, C. Robic, L. V. Elst,
R. N. Muller, Chem. Rev. 2008, 108, 2064.
[2] A. K. Gupta, M. Gupta, Biomaterials 2005, 26, 3995.
[3] O. J. Cayre, N. Chagneux, S. Biggs, Soft Matter 2011, 7, 2211.
[4] F. Tajifirooz, A. Davoodnia, M. Pordel, M. Ebrahimi,
A. Khojastehnezhad, Appl. Organomet. Chem. 2017, 32, e3930.
[5] S. Phadtare, A. Kumar, V. P. Vinod, C. Dash, D. V. Palaskar,
M. Rao, P. G. Shukla, S. Sivaram, M. Sastry, Chem. Mater.
2003, 15, 1944.
[36] A. Maleki, V. Eskandarpour, J. Iran Chem. Soc. 2019, 16, 1459.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
[6] S. Shylesh, V. Schnemann, W. R. Thiel, Angew. Chem. Int. Ed.
2010, 49, 3428.
[7] D. Wang, D. Astruc, Chem. Rev. 2014, 114, 6949.
[8] M. Mokhtary, J. Iran, Chem. Soc. 2016, 13, 1827.
[9] T. Cheng, D. Zhang, H. Li, G. Liu, Green Chem. 2014, 16, 3401.
[10] B. Karimi, F. Mansouri, H. M. Mirzaei, ChemCatChem 2015, 7,
1736.
[11] C. W. Lim, I. S. Lee, Nano Today 2010, 5, 412.
[12] (a)S. Payra, A. Saha, S. Banerjee, J. Nanosci. Nanotechnol.
2017, 17, 4432. (b)A. Maleki, Tetrahedron 2012, 68, 7827. (c)
A. Maleki, T. Kari, M. Aghaei, J. Porous Mater. 2017, 24, 1481.
(d)A. Maleki, RSC Adv. 2014, 4, 64169.
How to cite this article: Faroughi Niya H,
Hazeri N, Maghsoodlou MT. Synthesis and
characterization of Fe3O4@THAM-SO3H as a
highly reusable nanocatalyst and its application for
the synthesis of dihydropyrano[2,3-c]pyrazole
derivatives. Appl Organometal Chem. 2020;e5472.
https://doi.org/10.1002/aoc.5472
[13] B. Rác, A. Molnar, P. Forgo, M. Mohai, I. Bertóti, J. Mol. Catal.
A: Chem. 2006, 244, 46.