Fe3O4–cysteamine hydrochloride magnetic nanoparticles: New, efficient and recoverable nanocatalyst for Knoevenagel condensation reaction

Article abstract of DOI:10.1002/aoc.3795

Fe₃O₄ magnetic nanoparticles (MNPs) were obtained using a reduction–precipitation method. These MNPs were modified with cysteamine hydrochloride. This catalyst was characterized using a number of physicochemical measurements. The Fe<

Full text of DOI:10.1002/aoc.3795

Received: 21 December 2016
DOI: 10.1002/aoc.3795
Revised: 14 February 2017
Accepted: 14 February 2017
F U L L PA P E R
Fe3O4–cysteamine hydrochloride magnetic nanoparticles: New,
efficient and recoverable nanocatalyst for Knoevenagel
condensation reaction
Razieh Maleki | Eskandar Kolvari
| Mehdi Salehi | Nadiya Koukabi
Department of Chemistry, Semnan
University, PO Box 35195‐363 Semnan, Iran
Fe3O4
magnetic
nanoparticles
(MNPs)
were
obtained
using
a
reduction–precipitation method. These MNPs were modified with cysteamine
hydrochloride. This catalyst was characterized using a number of physicochemical
measurements. The Fe3O4–cysteamine MNPs, as an efficient and heterogeneous
catalyst, were successfully used for Knoevenagel condensation under mild condi-
tions. The activity of this nanomagnetic catalyst in the Knoevenagel condensation
of aromatic aldehydes and malononitrile is described. Easy preparation of the
catalyst, easy work‐up procedure, excellent yields and short reaction times are some
of the advantages.
Correspondence
Eskandar Kolvari, Department of Chemistry,
Semnan University, PO Box 35195‐363,
Semnan, Iran.
Email: kolvari@semnan.ac.ir
KEYWORDS
Fe3O4–cysteamine hydrochloride, heterogeneous catalyst, Knoevenagel condensation, organic magnetic salt
nanocatalyst
1 | INTRODUCTION
organic compounds.[7] For example, Zolfigol et al. used
modified MNPs for synthesis of tetrahydrobenzo[b]pyran
Magnetic nanoparticles (MNPs) are of interest for their appli-
cations in many areas, including biotechnology/biomedi-
cine[1] and especially catalysis because of their unique
magnetic and electronic properties.[2] Functionalized MNPs
have emerged as viable alternatives to conventional materials,
being robust, readily accessible and having high surface area,
which allows the design of many catalytic sites.[3] These
functionalized materials suggest an added advantage of being
magnetically separable, thereby eliminating the requirement
of catalyst filtration after completion of a reaction.[4] Among
the MNPs, magnetic iron oxide nanoparticles have large
surface‐to‐volume ratio and therefore have high surface
energies.[5] Bare iron oxide nanoparticles have high chemical
activity, and are easily oxidized in air, generally resulting in
loss of magnetism and dispersibility. For these reasons,
providing appropriate surface coating and developing some
effective protection strategies to keep the stability of iron
oxide MNPs are very important.[6] Magnetic iron nanoparti-
cles have many applications as catalysts in the synthesis of
derivatives.[8] Also, Hudson used iron MNPs for drug
delivery, tissue destruction and remote biological interfacing.[9]
The Knoevenagel condensation reaction is well known
for its vast potential for the synthesis of α,β‐unsaturated
compounds from active methylene compounds and carbonyl
compounds.[10] One of the most important properties of
Knovenagel condensations from a synthetic outlook is that
they offer a route to the formation of C═C bonds, in the
presence of basic catalyst or Lewis acid catalyst, such as
piperidine, diethylamine or corresponding ammonium
salt.[11] A wide array of catalysts, such as TiCl4,[12]
magnesium
fluoride,[13]
ZnCl2,[14]
Na2CaP2O7,[15]
chitosan,[16] ionic liquids[17] or guanidinium group,[18] have
been employed. Also, heterogeneous catalysts were used as
efficient catalysts for Knoevenagel condensation reactions.
For example, Bhaumik and co‐workers were able to
synthesize porphyrin‐based microporous organic polymer
Fe‐POP‐1. This catalyst was used as a base catalyst for the
Knoevenagel condensation of various aromatic aldehydes
Appl Organometal Chem. 2017;e3795.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.3795

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MALEKI ET AL.
with malononitrile.[19] They were also able to prepare amino‐
functionalized mesoporous materials to synthesize α,β‐unsat-
urated dicyano compounds via Knoevenagel condensation of
aromatic aldehydes and malononitrile.[20]
Cysteamine is a chemical compound with the formula
HSCH2CH2NH2. It is the simplest stable aminothiol and a
degradation product of the amino acid cysteine. It is often
used as the hydrochloride salt, HSCH2CH2NH3Cl. This
compound is used in the body to form the essential
SCHEME 1 Preparation of Fe3O4–cysteamine hydrochloride MNPs
FIGURE 1 XRD spectrum of Fe3O4–cysteamine hydrochloride
FIGURE 2 EDS spectrum of Fe3O4–cysteamine hydrochloride

MALEKI ET AL.
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biochemical coenzyme A by combining with pantothenate
and adenosine triphosphate.
2 | EXPERIMENTAL
This paper describes the synthesis of magnetite nanoparti-
cles without surfactant. The raw targets were prepared by a
reduction co‐precipitation method without argon or nitrogen
protection.[21] To improve the immobilized catalysts in this
procedure, we focused on MNP‐supported cysteamine. In
continuation of our research on the development of greener
protocols, new methodologies and nanocatalysis, we have
designed a new, simple and efficient method for the
functionalization of magnetite nanoparticles with cysteamine,
which catalyse the two‐component Knoevenagel condensation
reaction of aldehydes and malononitrile in ethanol–water.
2.1 | Materials and instrumentation
All starting materials were purchased from Merck and
Sigma‐Aldrich and used as received without further purifica-
tion. The morphology of the catalyst was studied using
scanning electron microscopy (SEM) with a Philips XL30
field emission scanning electron microscope (Royal Philips
Electronics, Amsterdam, The Netherlands) operating at
25 kV and transmission electron microscopy (TEM; CM30,
Philips, Netherland). Wide‐angle X‐ray diffraction (XRD)
measurements were performed at room temperature with a
Siemens D5000 (Siemens AG, Munich, Germany) using Cu
Ka radiation of wavelength 1.54 Å. Thermogravimetric anal-
ysis (TGA) was done using a Dupont 951 thermal analysis
instrument, heating from 25 to 1000 °C at a ramp of 5 °C
min−1 under nitrogen atmosphere. The specific surface area
and pore volume of the catalyst were calculated using the
Brunauer–Emmett–Teller (BET) and Barrett–Joyner–
Halenda methods, respectively. Energy‐dispersive X‐ray
spectroscopy (EDS; Philips XL‐30) was used for determina-
tion of elemental composition of the catalyst. The purity of
products was checked by TLC using commercial plates
coated with silica gel 60 F254 using n‐hexane–ethyl acetate
mixture as mobile phase. Melting points were recorded with
a Thermo Scientific 9100 instrument. Fourier transform
infrared (FT‐IR) spectroscopy was conducted with a
Shimadzu 8400 spectrometer in the range 400–4000 cm−1
using KBr plates. NMR spectra were measured in pure deu-
terated chloroform with a Bruker Advance 400 MHz instru-
ment with tetramethylsilane as the internal reference.
2.2 | Preparation of Fe3O4–Cysteamine MNPs
The Fe3O4 MNPs were synthesized by a reduction–precipita-
tion method according to a previously reported procedure.[21]
FIGURE 3 (a) TEM image and (b) SEM image of Fe3O4–cysteamine
hydrochloride
TABLE 1 Results of BET measurements of Fe3O4–cysteamine
hydrochloride
Surface area (m2 g−1
)
Total pore volume (cm3 g−1
)
FIGURE
hydrochloride
4
N2 adsorption isotherm of Fe3O4–cysteamine
84
0.2538

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MALEKI ET AL.
FIGURE 5 XPS analysis of Fe3O4–cysteamine hydrochloride
FIGURE 6 TGA curve of Fe3O4–cysteamine hydrochloride
FIGURE
7
Room temperature magnetization curves of (a)
nanomagnetic Fe3O4 and (b) Fe3O4–cysteamine hydrochloride
Synthesized MNPs (1 g) were dispersed in 20 ml of distilled
water. Cysteamine hydrochloride (1 g) dissolved in 40 ml of
water–ethanol (1:1) was added to the dispersed MNPs and
the reaction mixture stirred at room temperature. The cyste-
amine hydrochloride‐functionalized MNPs were then
isolated by simple magnetic decantation and successively
washed with water (20 ml) and methanol (20 ml) and dried
under vacuum at 60 °C for 2 h.

MALEKI ET AL.
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TGA, X‐ray photoelectron spectroscopy (XPS) surface
analysis and EDS. Figure 1 shows the XRD spectrum of
Fe3O4–cysteamine hydrochloride. The peak at 2θ = 35.8°
confirms the nanostructures of Fe3O4. Also, the broad peak
at 2θ = 15–30° may be related to cysteamine hydrochloride.
The crystal size of Fe3O4–cysteamine was determined using
the Debye–Scherrer equation. The results show that cubic
spinel structure of Fe3O4–cysteamine hydrochloride was
synthesized with a size of 40 nm.
SCHEME 2 Fe3O4–cysteamine hydrochloride‐catalysed Knoevenagel
condensation of aromatic aldehydes with malononitrile in ethanol–water
2.3 | General procedure for synthesis of
knoevenagel products using Fe3O4–cysteamine
hydrochloride as catalyst
According to Figure 2, the EDS analysis clearly confirms
the presence of cysteamine hydrochloride.
A mixture of aldehyde (0.5 mmol), malononitrile (0.5 mmol)
and Fe3O4–cysteamine hydrochloride (0.05 g) in a round‐
bottom flask containing 5 ml of ethanol was stirred at
50 °C using a magnetic stirrer for the required time. After
completion of the reaction monitored by TLC, the catalyst
was separated magnetically. The reaction mixture was
placed at room temperature until solidification occurred.
For further purification, the solid was recrystallized from
96% ethanol.
The size and the shape of the synthesized Fe3O4–cyste-
amine hydrochloride nanocatalyst were deduced from TEM
images. Typical TEM and SEM images of the magnetic
nanocatalyst are shown in Figure 3. According to Figure 3, the
size of nanoparticles in the TEM image (within 20–40 nm) is
in agreement with the SEM image (average of 40 nm).
The BET data show that surface area of the
Fe3O4–cysteamine hydrochloride nanocatalyst is 84 m2 g−1
and the total pore volume of the nanocatalyst is
0.2538 cm3 g−1 (Table 1). Also, the N2 adsorption isotherm
of this catalyst is shown in Figure 4. The Fe 2p XPS spectrum
contains two peaks. There are two strong peaks located at 757
and 772 eV, which are typical Fe 2p1/2 and Fe 2p3/2 XPS
signals of magnetite. The peaks corresponding to oxygen
(O 2 s) at 557 eV, carbon (C 1 s) at 290 eV and nitrogen
(N 1 s) at 447 eV are also clearly observed in the XPS
elemental survey of the catalyst (Figure 5).
3 | RESULTS AND DISCUSSION
3.1 | Synthesis and characterization of
nanocatalyst (Fe3O4–cysteamine hydrochloride)
The organocatalyst MNPs (Fe3O4–cysteamine hydrochloride)
were prepared from Fe3O4 and cysteamine by simple
mechanical stirring (Scheme 1). The synthesized catalyst
was characterized using XRD, FT‐IR spectroscopy, TEM,
vibrating sample magnetometry (VSM), BET measurements,
TGA was used to study the possible thermal stability and
degradation processes of nano‐Fe3O4–cysteamine hydrochlo-
ride. The TGA thermogram of nano‐Fe3O4–cysteamine
TABLE 2 Knoevenagel condensation in various solvents and with different amounts of Fe3O4–cysteamine hydrochloride
Entry
Solvent
Catalyst (g)
Temp. (°C)
Yield (%)
1
Solvent‐free
Solvent‐free
Ethanol
0.05
0.05
0.05
0.05
0.05
0.02
0.03
0.04
0.05
0.06
0.05
0.05
0.05
0.05
50
80
50
90
RT
50
50
50
50
50
40
50
100
70
Trace
Trace
50
2
3
4
Water
47
5
Ethanol
42
6
Ethanol–water
Ethanol–water
Ethanol–water
Ethanol–water
Ethanol–water
Dichloromethane
n‐hexane
60
7
66
8
70
9
93
10
11
12
13
14
94
—
42
PEG–water
Acetonitrile
—
—

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MALEKI ET AL.
TABLE 3 Knoevenagel condensation of various aromatic aldehydes with malononitrilea
Entry
Aldehyde
Yield (%)b
Time
M.p.)° C)
M.p. (reported) (°C)
1
93
20
83–85
82–85[22]
2
3
96
95
15
40
189–191
92–95
190–191[23]
94–95[24]
4
5
6
97
98
91
10
55
15
162–164
113–115
137–139
162–163[25]
113–114[26]
137–138[24]
7
92
10
106–108
102–103[27]
8
9
96
90
5
159–161
135–137
160[28]
25
134–135[29]
10
11
93
94
15
5
160–162
138–140
159–161[25]
136–137[30]
12
13
97
95
10
15
187–189
102–103
187–188[25]
99–100[30]
14
92
20
73–75
72[31]
(Continues)

MALEKI ET AL.
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TABLE 3 (Continued)
Entry
Aldehyde
Yield (%)b
Time
M.p.)° C)
M.p. (reported) (°C)
15
94
20
131–133
130[32]
16c
17c
92
94
20
20
118–119
131–134
116[33]
130[33]
aReaction conditions: Fe3O4–cysteamine hydrochloride (0.05 g), aromatic aldehydes (1 mmol), ethanol–water (1:1), 50 °C.
bYields are given for isolated products.
cWith dimedone (1 mmol).
hydrochloride is shown in Figure 6. Three thermal
degradation steps are characterized. The first decomposition
step is identified in the range 25–120 °C and this corresponds
to a loss of H2O. The weight loss in the second degradation
step of this catalyst corresponds to the range 250–400 °C
and this corresponds to loss of cysteamine hydrochloride.
The third decomposition step is identified in the range
415–675 °C showing the phase transformations which
can be assigned to the phase change of magnetite to
maghemite. The sum of these three degradation steps is
8.348% and this value gives direct evidence for the load-
ing of cysteamine hydrochloride on the surface of nano‐
Fe3O4 (Figure 6).
Figure 7 illustrates the magnetic curves of the initial
MNPs and cysteamine hydrochloride‐modified MNPs. The
magnetic properties of the uncoated Fe3O4 and
Fe3O4–cysteamine hydrochloride nanoparticles were
measured using VSM. From the M versus H curves, the
saturation magnetization (Ms) of uncoated MNPs is found
to be 70 emu g−1. For Fe3O4–cysteamine hydrochloride
MNPs, the magnetization is obtained as 60 emu g−1. This
reduced magnetization is mainly attributed to the existence
of cysteamine hydrochloride on the surface of the MNPs.
This interesting magnetic property could ensure that this
superparamagnetic nanocatalyst is easily manipulated using
a magnet in the separation process.
Knoevenagel condensation (Scheme 2). In the first step and
to optimize the reaction conditions, the prepared catalyst
was used for the promotion of the Knoevenagel condensation
of aromatic aldehydes with malononitrile, and the effect of
various solvents and solvent‐free conditions were compared
and also the effect of the catalyst load on the reaction yield
and time at thermal conditions. The results are summarized in
Table 2. On the basis of these results it can be concluded that
the best results can be obtained under the conditions shown
in Scheme 2.
To study the efficiency of Fe3O4–cysteamine hydrochlo-
ride in Knoevenagel condensation, various aromatic
aldehydes were reacted with malononitrile under the opti-
mal reaction conditions. The obtained results are summa-
rized in Table 3.
Reusability is one of the important criteria for an efficient
heterogeneous catalyst in organic transformations and makes
them useful for commercial applications. The recovered
nanocatalyst was reused five times for the Knoevenagel con-
densation reaction of aromatic aldehydes with malononitrile.
The results illustrated in Figure 8 show that the catalyst can
be used five times without significant loss in its activity.
3.2 | Optimization of Knoevenagel
condensation reaction catalysed by Fe3O4–
cysteamine hydrochloride
The synthesized and well‐characterized Fe3O4–cysteamine
hydrochloride MNPs were explored as a catalyst for
FIGURE
hydrochloride catalyst
8
Recycling
experiment
of
Fe3O4–cysteamine

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MALEKI ET AL.
[14] P. Shanthan Rao, R. V. Venkataratnam, Tetrahedron Lett. 1991, 32,
ACKNOWLEDGMENT
5821.
The authors are grateful to the Semnan University Research
Council for the partial support of this work.
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Commun. 2001, 2, 101.
[16] M. Zhang, A. Q. Zhang, X. H. Tang, Chin. J. Org. Chem. 2004, 24,
1106.
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How to cite this article: Maleki R, Kolvari E, Salehi
M, Koukabi N. Fe3O4–cysteamine hydrochloride
magnetic nanoparticles: New, efficient and recoverable
nanocatalyst for Knoevenagel condensation reaction.
Appl Organometal Chem. 2017;e3795. https//:doi.org/
10.1002/aoc.3795
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