Fe3O4@saponin/Cd: a novel magnetic nano-catalyst for the synthesis of β-aminoketone derivatives

Article abstract of DOI:10.1007/s13738-020-01918-x

A novel recyclable magnetic core–shell nanoparticles Fe₃O₄@saponin/Cd was synthesized by the combination of nano-Fe₃O₄@saponin with cadmium acetate. The structure, magnetic features, and morphology of magnetic nanoparticles (MNPs) Fe₃O₄@saponin/Cd were studied totally via different experiments, such as Fourier transform infrared (FT-IR) spectroscopy, energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), inductively coupled plasma (ICP), high-resolution transmission electron microscopy (HR-TEM), and Brunauer–Emmett–Teller (BET). It was found that the catalyst was active for the synthesis of?β-aminoketone derivatives via one-pot three-component Mannich-type reactions of ketones, aromatic aldehydes, aromatic amines under eco-friendly solvent, at room temperature. Furthermore, this catalyst can be easily recovered magnetically and can be reused for other runs without any reduction in the activity.

Full text of DOI:10.1007/s13738-020-01918-x

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-020-01918-x
ORIGINAL PAPER
Fe3O4@saponin/Cd: a novel magnetic nano‑catalyst for the synthesis
of β‑aminoketone derivatives
Marzieh Kiani1 · Hossein Anaraki‑Ardakani2 · Neda Hasanzadeh1 · Ayeh Rayatzadeh1
Received: 16 October 2019 / Accepted: 18 March 2020
© Iranian Chemical Society 2020
Abstract
A novel recyclable magnetic core–shell nanoparticles Fe3O4@saponin/Cd was synthesized by the combination of nano-
Fe3O4@saponin with cadmium acetate. The structure, magnetic features, and morphology of magnetic nanoparticles (MNPs)
Fe3O4@saponin/Cd were studied totally via diferent experiments, such as Fourier transform infrared (FT-IR) spectroscopy,
energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray difraction (XRD), vibrating sample
magnetometer (VSM), scanning electron microscopy (SEM), inductively coupled plasma (ICP), high-resolution transmis-
sion electron microscopy (HR-TEM), and Brunauer–Emmett–Teller (BET). It was found that the catalyst was active for the
synthesis of β-aminoketone derivatives via one-pot three-component Mannich-type reactions of ketones, aromatic aldehydes,
aromatic amines under eco-friendly solvent, at room temperature. Furthermore, this catalyst can be easily recovered magneti-
cally and can be reused for other runs without any reduction in the activity.
Keywords Nano-Fe3O4 · Saponin · Cadmium acetate · β-aminoketones · Green chemistry
Introduction
spontaneously when exposed to acids and aqueous solu-
tions. To overcome the above-mentioned limitations, the
surface of MNPs must be covered by a protective agent
such as silica, polymer, or carbon [6, 7].
The heterogeneous catalysts made out of organic and
inorganic materials have recently been introduced by
researchers who possess the advantages of both homo-
geneous and heterogeneous catalysts. Furthermore, the
use of MNPs as support in heterogeneous catalysis is
a growing field of research. In this area, MNPs appear
as an ultimate nanosupport due to their ease of recov-
ery [1, 2]. Fe3O4 NPs, for their strong magnetic proper-
ties, high chemical stability, being abundant, effortless
preparation via co-precipitation, and low toxicity which
are the most common MNPs, have been more extensively
studied as the core magnetic support by researchers [3,
4]. It should be mentioned that pure Fe3O4 MNPs, with
the high surface area to volume ratio, are highly chemi-
cally active and suffer from an inherent instability [5].
They are very sensitive to oxidation and tend to aggregate
Quillaja Saponaria (sapogenin) is a huge evergreen tree,
which is native to China, Peru, and the arid zones of Chile.
Leaves of this tree are shiny, leathery, and its bark is thick
[8]. Its bark is rich in saponins, plant glycosides, which
are widely distributed in the plant and marine animal king-
doms. Chemically, saponins are steroids, or triterpene gly-
cosides, possessing a wide variety of activities, which are
cancer-related, anti-infammatory, anti-allergic, and anti-
viral activities with efects on the physiology of the car-
diac, and blood systems, as well as molluscicidal activities
[9, 10]. The Quillaja saponaria’s bark is rich in industrial
triterpenoid saponin. Saponin is the general name of this
chemical, and about 20 to 35% of the chemical is composed
of sapogenin. Saponin is mainly cellulose, especially the
hydroxyl groups in cellulose, which provide active sites for
numerous attractive chemical modifcations [11]. There-
fore, cellulose in saponin can be used as an efcient sup-
porting agent for the synthesis of various heterogeneous
catalysts [12, 13].
* Hossein Anaraki-Ardakani
hosseinanaraki@yahoo.com
1
Department of Chemistry, Ahvaz Branch, Islamic Azad
University, Ahvaz, Iran
The Mannich-type reactions are a significant car-
bon–carbon bond formation in organic synthesis. They
2
Department of Chemistry, Mahshahr Branch, Islamic Azad
University, Mahshahr, Iran
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
provide β-aminoketones compounds, which are vital inter-
mediates for the development of different natural products
containing nitrogen and pharmaceutical products [14–17].
Previously, some of the β-aminoketone compounds had
been catalyzed by heteropolyacids [18], diaryliodonium
salts [19], saccharose [20], bismuth nitrate [21], starch
[22] solution, proline [23–25], InCl3 [26], Yb(OiPr)3 [27],
calixarenes [28], and carboxyl-functionalized poly(ionic
liquid) (CFPIL) [29]. The discussed catalyst has some
drawbacks, like long reaction duration, low yield of prod-
ucts, toxicity, and lack of recoverability. Therefore, it is
required to find better alternatives that can proceed under
mild, simple, efficient, and environmentally reaction-
friendly conditions.
Methods
Preparation of magnetic nanoparticles (Fe3O4)
MNPs were precipitated in an alkali solution of Fe(III) and
Fe(II) (molar ratio 2:1) at 80 °C via standard co-precipitation
method reported by Liu et al. [30].
FeCl3·6H2O (10 mmol, 2.7 gr) and FeSO4·7H2O
(10 mmol, 1.39 gr) were slowly added to a vortex of deoxy-
genated distilled water (100 ml). The dispersion was vigor-
ously stirred at 80 °C under N2 protection. In the next step,
the reaction mixture was suddenly incorporated into ammo-
nium hydroxide by a volume of 7.5 mm. Adding the base to
the solution of Fe2+/Fe3+ salt led to the formation of MNPs,
which was a black precipitate. The reaction proceeded for
another 60 min, and the mixture was cooled to room tem-
perature. The resulting black precipitate was isolated using
the implementation of an external magnetic feld. It was then
washed four times with water followed by drying in vacuum
at room temperature [31, 32].
Hence, we report Fe3O4@saponin/Cd as a strong and attrac-
tive biological heterogeneous nano-catalyst for the synthesis
of β-amino ketone derivatives by a three-component reaction
of ketones, aromatic aldehydes, and aromatic amines under
mild reaction conditions.
Experimental
Preparation of nano‑Fe3O4@saponin
General
A mixture of 1.5 g synthesized nano-Fe3O4 and 2.5 g sapo-
nin was stirred in 20 mL of ethanol at ambient temperature
for 20 min. After stirring the mixture, the product was gath-
ered by a magnet, and then it was washed with ethanol. After
this process, a 3.96 g product was obtained.
All compounds used in this study were purchased from
Merck or Sigma-Aldrich brand. They were all highly
pure. FT-IR apparatus used in this study was able to detect
spectra in the range of 4000 to 400 cm−1 using the Perki-
nElmer spectrometer by KBr disks. The melting point of
compounds was measured via the Electrothermal-9200
apparatus. Reactions were monitored by thin-layer chro-
matography (TLC) performed on 0.25-mm Merck TLC
silica gel 60 F254 plates, using UV light as a visualizing
agent. TGA tests were conducted on a LINSEIS MODEL
1600 PT, which is a thermal analyzing apparatus with a
heating speed of 5 °C per each minute under atmospheric
condition. XRD was analyzed using a Philips apparatus
by radiation of Cu/Kα within a 1.54 Å wavelength on the
powdered product. BET was analyzed via BELSORP MINI
II apparatus. ICP was performed using Agilent device
(model: ICP-7900). HR-TEM images were captured by FEI
apparatus with model of TEC9G20. SEM was obtained
Preparation of nano‑Fe3O4@saponin/Cd
0.3 gr of synthesized nano-Fe3O4@saponin powder and
0.348 g of Cd(CH3COO)2·2H2O (1:1 w/w) were dispersed
in 10 ml of ethanol at ambient temperature for 30 min. Then,
the solvent was evaporated at room temperature; then, its
magnetic characteristic was investigated. Finally, the product
was rewashed with ethanol for more purifcation and dried
at room temperature.
Synthesizing procedure for the β‑aminoketones
A mixture of 1.1 mmol of ketones, 1 mmol of aromatic
amines, 1 mmol of aromatic aldehydes, and 0.08 g of nano-
Fe3O4@saponin/Cd was poured in 15 ml of EtOH at ambient
temperature. After completion of the reaction (monitored by
TLC), the catalyst was collected with an external magnet.
Then, the reaction mixture was heated to obtain the crude
product. After the purifcation process of the crude product
by recrystallization from ethanol/acetone (v/v=3:2), the cor-
responding compounds were obtained.
using a Mira III. H and 13C NMR spectra were recorded
1
by Bruker DRX-500 Avance spectrometer at the solution in
DMSO-d6 using TMS as an internal standard. Analysis of
the EDS was conducted for the mapping of the nanocom-
posite elements. Two minutes before the test commenced, a
10 mA layer of gold was used to cover the surface of sam-
ples. The magnetic characteristics of samples were identi-
fed via VSM (SAMX; Model: MIRA III) at the ambient
temperature.
Spectral data for new Compounds 4n-q
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Journal of the Iranian Chemical Society
3‑(4‑Bromo‑phenylamino)‑1,3‑diphenyl‑propan‑1‑one
(Table 3, Entry 4n) Mp 177–179 °C, IR (KBr, cm−1): 3412,
1676, 1605, 1515, 1312, 858, 767. Analyses: Calcd. for
C21H18BrNO: C, 66.33; H, 4.77; N, 3.68; O, 4.21%. Found:
C, 66.36; H, 4.80; N, 3.64%. 1H NMR (300 MHz, DMSO):
δ=7.98–6.60 (m, 14H), 6.34 (d, J=6 Hz 1H), 5.10 (m, 1H),
3.55 (m, 2H). (13CNMR,75 MHz, CDCl3): δ=44.5, 55.15,
116.85, 116.93, 126.05, 127.58, 128.4, 128.43, 128.64,
131.89, 133.05, 137.95, 141.58, 146.88, 198.15 ppm.
1H), 2.23 (s, 3H). (13CNMR,75 MHz, CDCl3): δ=21.01,
46.38, 54.43, 114.04, 120.79, 127.84, 128.15, 128.73,
128.92, 129.02, 129.64, 129.80, 129.84, 134.85, 136.12,
198.48 ppm.
3‑(4‑Nitro‑phenylamino)‑1‑phenyl‑3‑p‑tolyl‑propan‑1‑one
(Table 3, Entry 4q) Mp 163–165 °C, IR (KBr, cm−1): 3392,
1671, 1600, 1513, 1313, 862, 768; Analyses: Calcd. for
C22H20N2O3: C, 73.32; H, 5.59; N, 7.77%; Found: C, 73.38;
H, 5.51; N, 7.81%; 1H NMR (300 MHz, CDCl3): δ=7.97–
6.58 (m, 13H), 5.11 (m, 1H), 4.35 (s, 1H), 3.71 (m, 1H),
3.38 (m, 1H), 2.24 (s, 3H). (13CNMR,75 MHz, CDCl3):
δ=21.05, 45.55, 53.94, 112.12, 126.56, 127.74, 128.15,
128.36, 128.77, 129.75, 135.24, 137.63, 137.99, 138.23,
152.18, 197.85 ppm.
3‑(4‑Bromo‑phenylamino)‑3‑(4‑chloro‑phenyl)‑1‑phe‑
nyl‑propan‑1‑one (Table 3, Entry 4o) Mp 171–173 °C, IR
(KBr, cm−1): 3376, 1681, 1598, 1510, 1301, 750; Analy-
ses: Calcd. for C21H17BrClNO: C, 60.82; H, 4.13; N, 3.38;
1
Found: C, 60.87; H, 4.17; N, 3.31%. H NMR (300 MHz,
CDCl3): δ=7.91 (s, 2H), 7.88 (d, J=1.4 Hz, 1H), 7.59 (m,
2H), 7.45 (t, J=7.83 Hz, 2H), 7.37–7.27 (m, 2H), 7.19–7.16
(m, 2H), 6.43–6.4 (m, 2H), 4.93 (br, 1H), 4.65 (s, br, 1H),
3.44 (m, 2H). (13CNMR,75 MHz, CDCl3): δ=44.92, 54.18,
109.83, 115.46, 127.73, 128.14, 128.78, 129.05, 131.85,
133.16, 133.67, 136.45, 140.93, 145.69, 197.79 ppm.
Results and discussion
Nano-Fe3O4@saponin/Cd was synthesized within two steps.
Firstly, nano-Fe3O4 was synthesized by co-precipitation of
Fe2+ and Fe3+ ions, and then it was mixed with saponin.
Finally, it was used as a magnetic support to bond cadmium
(Scheme 1).
3‑(4‑Bromo‑phenylamino)‑1‑phenyl‑3‑p‑tolyl‑pro‑
pan‑1‑one (Table 3, Entry 4p) Mp 175–177 °C, IR (KBr,
cm−1): 3395, 1673, 1602, 1513, 1311, 760; Analyses: Calcd.
for C22H20BrNO: C, 67.01; H, 5.11; N, 3.55%; Found: C,
The magnetically heterogeneous nano-catalyst, Fe3O4@
saponin/Cd, is characterized by FT-IR spectroscopy, VSM,
EDS analysis, XRD, SEM, ICP, BET, and TGA.
The results obtained from FT-IR spectroscopy of (A)
nano-Fe3O4, (B) nano-Fe3O4@saponin, (C) nano-Fe3O4@
1
67.11; H, 5.18; N, 3.58%; H NMR (300 MHz, CDCl3):
δ=7.94–6.44 (m,13H), 6.40 (m, 1H), 4.9 (m, 1H), 3.6 (d, d,
J=12, J=4.5 Hz, 1H), 3.34–3.23 (d, d, J=12, J=4.5. Hz,
H
H
H
H
H
OH
HO
OH
O
N
H
N
Fe2+
H
HO
HO
O
H
H
O
O
H
H
H
H
O
nano- Fe3O4
O
O
O
O
O
Fe2+
O
OH
O
O
CH2CH3OH
Fe2+
O
Fe2+
O
O
O
O
HO
OH
O
Fe2+
O
O
Fe2+
OH
Fe2+
OH
HO
OH
Cd
HO
Saponin
OH
OH
OH
Cd(CH3COO)2
Ethanol, rt
30 min
Fe3O4 NP
Ethanol
HO
HO
Fe3O4 NP
+
Fe3O4 NP
rt, 20 min
Saponin
OH
HO
OH
Scheme 1 Preparation of nano-Fe3O4@saponin/Cd
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Journal of the Iranian Chemical Society
saponin/Cd are shown in Fig. 1. The existence of the stretch-
ing vibration of Fe–O was concluded by an obvious signal
in 585 cm−1 in FT-IR spectroscopy of nano-Fe3O4. Further-
more, the broadness of the band at the range within 3300 to
3500 cm−1 has resulted from stretching vibrations of OH
group. The existence of Fe–O stretching vibration in con-
junction with absorptions of nano-Fe3O4@saponin indicates
that the magnetic nano-Fe3O4 is covered by saponin. Wide-
band at 3383 cm−1 as a result of the OH groups’ stretch-
ing vibrations in addition to the absorption bands around
2925 cm−1 demonstrates the stretching vibrations of the C–H
bonds, and the 1619 cm−1 band corresponds to the H–O–H
bending vibration. The absorption bands around 1065 and
1100 cm−1 demonstrate the vibrations of the C–O bonds.
The FT-IR spectrum of nano-Fe3O4@saponin/Cd shows
a characteristic peak at 673.15 cm−1 that may be corre-
sponding to stretching vibrations of Fe–O; the absorption
bands around 1021.79 cm−1 demonstrate the vibrations of
the C–O bonds. The formed Cd–O is characterized by an
intense and very broad IR band resolved as shoulders at
about 1417.87 cm−1. The 1564.50 cm−1 band corresponds
to the H–O–H bending vibration. The stretching vibrations
of O–H bonds are observed at 3439.42 cm−1.
42.7496°, 52.6891°, 56.3597°, and 61.64854° with FWHM
equal to 0.4723, 0.4723, 0.4723, 0.7872, 0.6298, and 0.6298
correspond, respectively, to the cubic structure of the pure
Fe3O4 patch described in the literature (Fig. 2a) [33]. The
same peaks were also observed on the XRD difraction pat-
tern of nano-Fe3O4@saponin, which indicates the preser-
vation of the structure of the crystalline spinel ferrite core
during the process of cellulose coating.
Moreover, the other different peaks at 2Ө = 19.5°,
21.3°, 23.5°, and 27.1° are related to the saponin coating
of nano-Fe3O4 (Fig. 2b). The XRD of nano-Fe3O4@sapo-
nin/Cd pattern shows that the structure is amorphous. The
peaks at 2Ө = 17°, 19.3°, 25.4°, 27° were also observed
in the Fe3O4@saponin (Fig. 2c). The difraction peaks at
2Ө=18.5°, 49°, 53.5° correspond to cadmium cores and the
sharp peak at around 2Ө=18.1°, 23.2°, 34°, 40.5°, 44.5°,
and 53.9° indicates the existence of nano-Fe3O4@saponin
and bonding of Cd to saponin shell.
TGA results in the temperature range of 0–800 °C are
shown in Fig. 3. The TGA (A) is related to nano-Fe3O4@
saponin. Curve A shows three mass-loss steps. The frst
weight loss was small (about 12.64%) and was occurred in
the range of 20 to 135 °C, which is related to the removal
of moisture and solvent of the catalyst. Afterward, the
weight loss observed in two steps, the main weight loss was
about 35.27% and observed in the range of 170–510 °C. It
is related to the decomposition of saponin units through
the formation of cellulose and other compounds. The fnal
weight loss is between 640 and 800 °C. The TGA (B) is
related to the nano-Fe3O4@saponin/Cd curve. It shows two
In comparison with nano-Fe3O4@saponin, bonding Cd to
the Saponin, the peak corresponding to wagging vibration
of Cd–O is observed at 1417.87 cm−1.
Phase purity and structure of nano-Fe3O4 (A) nano-
Fe3O4@saponin (B) and nano-Fe3O4@saponin/Cd (C) are
studied by means of high angle XRD (Fig. 2). The bare
Fe3O4 shows difraction peaks at 2Ө=30.3821°, 35.7917°,
Fig. 1 FT-IR spectra of a nano-
Fe3O4, b nano-Fe3O4@saponin,
c nano-Fe3O4@ saponin/Cd
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Journal of the Iranian Chemical Society
Fig. 2 XRD patterns of the a nano-Fe3O4, b nano-Fe3O4@saponin, c nano-Fe3O4@saponin/Cd
Fig. 3 Thermogravimetric anal-
ysis pattern of a nano-Fe3O4@
saponin, b nano-Fe3O4@
saponin/Cd
steps of mass loss. The frst weight loss from 0 to 63 °C is
related to the removal of moisture and solvent and water of
the catalyst. The second weight loss is the main weight loss,
which occurred in the range of 63–520 °C. It is related to
metals and some organic compounds.
EDS results confrm that the nano-Fe3O4 and saponin were
combined.
The existence of the expected elements in the structure of
the nano-Fe3O4@saponin/Cd was approved by EDS analysis,
which is shown in Fig. 5. The EDS results clearly confrm
the presence Fe, O, Cd, and C elements in this catalyst. The
results indicate that the catalyst has been made.
In order to determine the content of the elements, EDS
analysis was conducted on nano-Fe3O4@saponin, results of
which are shown in Fig. 4. The results of EDS nano-Fe3O4
@ saponin indicate the presence of C, Fe, and O. Also, the
The magnetic properties of nano-Fe3O4 (A), nano-
Fe3O4@saponin (B), and nano-Fe3O4@saponin/Cd (C)
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Journal of the Iranian Chemical Society
Fig. 4 EDS diagram of nano-
Fe3O4@saponin
Fig. 5 EDS diagram of nano-
Fe3O4@saponin/Cd
less than its bulk counterparts (92.0 emu/g) [34]. The
nano-Fe3O4@saponin/Cd magnetization was less than
30.0 emu/g of the particles. Therefore, the result showed
that its magnetization characteristic is lower than nano-
Fe3O4. This might have resulted from the formation of a
saponin shell and Cd shell as a double layer around the
nano-Fe3O4 core.
The morphology and size of the Fe3O4@saponin/Cd were
investigated by SEM, and Fig. 7 indicates that the dimen-
sions of Fe3O4@saponin/Cd are between 21 and 44 nm.
HR-TEM images of the catalyst are shown in Fig. 8.
Figure 8a, b illustrates that Fe3O4@saponin/Cd MNPs are
spherical in shape, dimension of which ranging from 21 to
44 nm. The saponin modifcation process of Fe3O4 leads to
the formation of a core–shell structure and confrms the for-
mation of a saponin layers with thickness of about 7 nm. The
TEM (Fig. 8a) observation indicates that Cd-coated Fe3O4/
saponin has average diameter ranging about 33 nm.
N2 adsorption–desorption isotherms of nano-Fe3O4@
saponin and nano-Fe3O4@saponin/Cd are shown in Fig. 9.
Fig. 6 Magnetization loops of a nano-Fe3O4, b nano-Fe3O4@saponin
and c nano-Fe3O4@saponin/Cd
were characterized at room temperature by VSM, and their
curves are shown in Fig. 6. All of the samples indicate a
typical super paramagnetic behavior. So, the saturation
magnetization of NPs is 70.0 emu/g (Fig. 6a), which is
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Journal of the Iranian Chemical Society
Fig. 7 SEM image of synthesized Fe3O4@saponin/Cd MNPs
Based on the IUPAC classifcation, the samples exhibit the
type of IV curves, which is corresponded to mesoporous
materials. The nitrogen adsorption–desorption isotherms
exhibit that the surface area of Fe3O4@saponin and Fe3O4@
saponin/Cd is 8.9317 and 3.3845 m2 g−1, respectively. The
pore diameter and pore volume of the mesoporous materials
indicates a marked decrease as a result of grafting organic
layers and Cd complex on the surface of the saponin. These
results indicate that due to the presence of the large organic
moieties within the pore channels of mesoporous saponin@
Cd complex loading appears as a thin layer on the inner
surface of Fe3O4. The surface properties of the synthesized
materials are given in Table 1.
To illustrate the magnetic properties of the synthesized
catalyst, the nano-Fe3O4@saponin/Cd was dispersed in
ethanol, which made a dark dispersion. In the presence of
an external magnetic feld, the nano-Fe3O4@saponin/Cd
was completely gathered on one side of the reservoir wall
(Fig 10).
Fig. 8 a HR-TEM of synthesized catalyst at 50 nm scale. b. HR-TEM
of synthesized catalyst at 100 nm scale
The catalytic activity of nano-Fe3O4@saponin/Cd was
investigated for synthesis of β-aminoketones derivatives
via one-pot three-component Mannich reaction of aromatic
amines, aromatic aldehydes, and ketones in ethanol at room
temperature. (Scheme 2).
Firstly, for the optimization of the reaction conditions,
the model reaction was carried out by using acetophenone,
aniline, and benzaldehyde in the presence of nano-Fe3O4,
nano-Fe3O4@saponin, and nano-Fe3O4@saponin/Cd as
catalyst. It was found that nano-Fe3O4@saponin/Cd was the
most efcient catalyst for the reaction in ethanol at ambi-
ent temperature. (Table 2, entry 4). However, only a trace
amount of the product was formed in the absence of catalyst
(Table 2, entry 1).
Fig. 9 N2 adsorption–desorption isotherms of nano-Fe3O4@saponin
(a) nano-Fe3O4@saponin/Cd (b)
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Journal of the Iranian Chemical Society
Table 1 Surface properties of
nano-Fe3O4@saponin and nano-
Fe3O4@saponin/Cd
Sample
SBET(m2/g)
Pore diam by BJH method Pore vol (cm3/g)
(nm)
Nano-Fe3O4@saponin
Nano-Fe3O4@saponin/Cd
8.9317
3.3845
1.98
1.65
0.067303
0.015916
Fig. 10 Photographs of aqueous
suspension of nano-Fe3O4@
saponin/Cd before a and after b
magnetic capture
R3
O
O
NH
CH3
NH2
CHO
R2
R1
R1
or
nano-Fe3O4@saponin/Cd
+
+
or
O
EtOH , R.T
R3
R2
R3
R3
R2
HN
O
HN
O
R2
+
R1
R1
2
3
R1
1
4a-q
Scheme 2 One-pot Mannich reaction of ketones, aromatic aldehydes, and aromatic amines catalyzed by nano-Fe3O4@saponin/Cd at room tem-
perature
To improve the yield of the target product, we car-
ried out the test reaction in the presence of various sol-
vents, and the results are given in Table 2 As shown in
Table 2, ethanol has been found to be the best solvent
among other solvents (toluene, xylene, CH3CN, MeOH,
CHCl3, DMF, and H2O). Then, the optimization of nano-
catalyst amounts was carried out in the model study by
using different amounts of the nano-Fe3O4@saponin/
Cd in ethanol at room temperature The higher yield was
obtained by increasing the amount of catalyst from 0.01
to 0.08 g (entry 13–21). However, a further increase in
catalyst amount from 0.08 to 0.1 g did not signifcantly
increase the yield of the product. Hence, the optimum con-
centration of nano-Fe3O4@saponin/Cd was chosen 0.08 g
in the model reaction (entry 20). We also investigated the
reaction temperature and found out that when the reaction
temperature was increased, no improved the amount of
yield. (entry 23–26)
In order to demonstrate the efectiveness of this method
and to study the scope and generality of the reaction, vari-
ous ketones, aromatic amines, and aromatic aldehydes were
examined, and the results are given in Table 3.
Compounds 4n-q were new and their structures
were deduced by elemental and spectral analysis. Other
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Journal of the Iranian Chemical Society
Table 2 Optimization of
condition for condensation
of acetophenone (1.1 mmol);
aniline (1 mmol); and
Entry
Catalyst
Temp (°C)/solvent
Time (h)
Weight (g)
Isolated
yield
(%)a
benzaldehyde (1 mmol)
1
2
3
4
5
6
7
8
No catalyst
Nano-Fe3O4
Nano-Fe3O4@saponin
r.t/EtOH
r.t/EtOH
r.t/EtOH
r.t/EtOH.
r.t/MeOH
r.t/CHCl3
r.t/Xylene
r.t/DMF
120 °C/None
r.t/CH3CN
r.t/Toluene
r.t/H2O
r.t./EtOH
r.t./EtOH
r.t./EtOH
r.t./EtOH
r.t./EtOH
r.t./EtOH
r.t./EtOH
r.t./EtOH
r.t./EtOH
r.t./EtOH
40/EtOH
60/EtOH
70/EtOH
Ref/EtOH
12
7
3
3
3
3
3
3
3
3
3
3
7
7
7
6
6
5
5
3
3
3
3
2.30
2.10
1.30
–
Trace
60
48
93
65
40
35
55
65
0.09
0.09
0.08
0.08
0.08
0.08
0.08
0.08
0/08
0.08
0.08
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
Nano-Fe3O4@saponin/Cd
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
70
Trace
Trace
53
61
68
73
80
86
91
93
93
90
93
93
86
80
0.08
0.08
0.08
0.08
aIsolated yields
compounds (4a-m) were known, and their structures were
deduced by comparison of melting points and spectral data
with authentic samples [14–29].
Reusability and leaching study of the catalyst
One of the signifcant properties of this nano-catalyst is reus-
ability; reusability of this catalyst was also studied for three-
component Mannich reaction of acetophenone, aniline, and
benzaldehyde under optimized conditions, results of which
are shown in Fig. 11. The magnetic nature of the catalyst
allowed its easy separation by magnet, after fnishing the
reaction. The catalyst was washed with ethanol three to four
times and dried at room temperature. Then, the recovered
catalyst was reused in the next cycles. As shown in Fig. 11,
the catalyst can be reused up to 4 runs but products yield
decreases from 93 to 78%.
Suggested mechanism for the synthesis of
β-aminoketones is shown in Scheme 3.
It is reasonable to assume that for the frst step, mag-
netic nano-catalyst bonds with carbonyl of aldehyde 2 and
makes it active. Then, it attacks to the nucleophilic of amin
3 to generate intermediate 5, which will lose one mole of
water to convert to imine 6. Then, the enol form 9 (in the
presence of tautomerization of ketone 1 in nano-catalyst)
reaction with imine 6 leads to the fnal product 4.
Finally, in order to show the efciency and generality
of this methodology, we compared this method with previ-
ously reported catalysts in the synthesis of compounds 4 l.
From comparison with the results given in Table 4, it was
found that nano-Fe3O4@saponin/Cd is the most efcient
catalyst with respect to reaction times, temperature, and
yield of the products (Table 4).
Furthermore, according to results obtained from ICP
analysis, the amount of cadmium in the virgin catalyst
is found to be 1.99 × 10−3 mol/g. After conducting the
reaction using this catalyst, the same test was performed
on the recovered one (4 runs), which showed that the Cd
concentration has reduced to 1.97 × 10−3 mol/g.
1 3

Journal of the Iranian Chemical Society
Table 3 Synthesis of β-aminoketone derivatives by nano-Fe3O4@saponin/Cd
Entry
Ketone
R2
R3
Time (h)
Yield (%)
Anti/syn
Mp. (°C)
Lit. mp. (°C)
4a
4b
4c
4d
4e
4f
4 g
4 h
4i
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
4-methylcyclohexanone
4-methylcyclohexanone
4-methylcyclohexanone
4-methylcyclohexanone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
1-naphthyl
2-naphthyl
1-naphthyl
4-Br
4-Cl
3-NO2
4-F
H
H
4-CH3
H
4-CH3
H
H
H
H
H
H
H
4-CH3
4-Br
4-Br
4-Br
4-NO2
1
1
99
99
94
93
95
90
91
99
97
98
83
93
89
97
91
90
87
99/1
99/1
97/3
98/2
98/2
93/7
82/18
95/5
97/3
99/1
99/1
–
170–172
127–128
135–137
109–111
119–121
160–162
118–120
131–133
168–170
174–176
144–146
166–168
161–162
177–179
171–173
175–177
63–165
171–173 [35]
129–131 [36]
137–139 [37]
109–110 [38]
119–120 [39]
163–165 [40]
–
132–135 [35]
169–172 [35]
174–178 [35]
146–147 [35]
168–169 [41]
160–161 [42]
[This work]
[This work]
[This work]
[This work]
1.10
50 (min)
45 (min)
1.30
1.20
55 (min)
1
1
1.10
3
4
3
3.30
3.30
3.50
H
1-naphthyl
2-naphthyl
2-Cl
4j
4 k
4 l
4 m
4n
4o
4p
4q
H
4-OCH3
H
4-Cl
4-CH3
4-CH3
–
–
–
–
–
Reaction conditions: ketone (1.1 mmol), amine (1 mmol), aldehyde (1 mmol); catalyst (0.08 g)
All reactions were obtained in ethanol at room temperature
To investigate the leaching of catalyst, a hot filtration
test has been conducted in the coupling of acetophenone
with 4-chlorobenzaldehyde and 4-bromoaniline. In this
work, 51% of yield product was obtained after reaction
halftime. Also, the same reaction was done, and after the
reaction halftime (110 min), the catalyst was gathered,
and then the filtrated mixture was allowed to continue
until the reaction end-time (220 min). In this step, 52%
of the product was produced. These tests confirm that the
leaching of the catalyst does not occur.
FT-IR spectroscopy was performed on the recovered
catalyst, which illustrates that the change in functional
groups of catalyst was negligible (Fig. 14).
Conclusions
In conclusion, we have described the characterization
and preparation of nano-Fe3O4@saponin/Cd as a novel
core–shell magnetic heterogeneous catalyst in good yields.
The catalytic activity of this catalyst was examined in the
synthesis of β-aminoketones derivatives through the one-
pot three-component reaction of aromatic aldehydes, aro-
matic amine, and ketones in ethanol. The most important
advantage of this protocol is that the materials used for this
protocol are readily accessible. Furthermore, the reaction
is conducted at room temperature and produces high yield
with no byproduct. Also, magnetic separation and reusability
of this catalyst are from other advantages of the described
protocol.
XRD, VSM, FT-IR, and ICP analyses were conducted
on the recovered catalyst after forth run. The results
obtained from these tests are illustrated in Figs. 12, 13,
and 14.
According to XRD data for recovered catalyst, which
are illustrated in Fig. 12, structure of the synthesized
catalyst did not change intensely after being recovered.
As shown in Fig. 13, the magnetic strength of the cata-
lyst has decreased slightly after recovery as compared to
original one.
1 3

Journal of the Iranian Chemical Society
Cd
Cd
Saponin
Cd
Saponin
Saponin
Fe3O4
FFee O
3O4 NP
3
4
R2
R2
O
NH2
OH
HN
N
H
R3
+
R3
R3
5
R2
6
Cd
Cd
Cd
Saponin
Cd
Saponin
Cd
Saponin
OCd
Saponin
Saponin
2
3
Fe3O4 NP
FFee O
3O4 NP
3
4
FFee O
3O4 NP
3
4
R2
Cd
Saponin
Cd
H
Saponin
O
Fe O
Fe3O4 NP
N
3
4
O
O
+
R1
R1
R3
R1
9
6
1
8
R2
HN
O
R1
R3
4
Scheme 3 Mechanism for formation of β-aminoketones in the presence of nano-Fe3O4@saponin/Cd as catalyst
Table 4 Comparison of the
efciency of nano-Fe3O4@
saponin/Cd with that of the
reported catalysts for the
synthesis of 1,3-diphenyl-3-
phenylamino-propan-1-one
Entry
Catalyst
Amount of catalyst
Tempera- Time (h)
ture (°C)
Yield (%) Refa
1
2
3
4
5
6
7
8
9
Cu/NH2-SBA-15
Diaryliodonium(III)
Citric acid
Carbon-based solid acid
H3PW12O30
CFPIL-1
PS-SO3H
BiNO3
[CellFemBen]CSA/EtOH
nano-Fe3O4@saponin/Cd
50 mg
30
rt
rt
rt
rt
10
24
10
3:45
18
5
90 [43]
83 [19]
90 [44]
90 [45]
76 [18]
70 [29]
75 [46]
89 [21]
10 mol %
20 mol%
0.1 g
0.691 g
0.032 g
0.08 g
10 mol%
1.63 mol%
0.08 g
rt
30
rt
rt
24
4
5
92 [47]
93 [present work]
10
rt
3
Reaction conditions: acetophenone (1.1 mmol); aniline (1 mmol); benzaldehyde (1 mmol)
All reactions were obtained in ethanol at room temperature
aIsolated yields
1 3

Journal of the Iranian Chemical Society
Fig. 11 Recycling experiment
of nano-Fe3O4@saponin/Cd in
the synthesis of β-aminoketones
reaction
100
90
80
70
60
50
40
30
20
10
0
93
91
86
78
1
2
3
4
Fig. 12 XRD of recovered
catalyst
Fig. 13 VSM of recovered
catalyst
1 3

Journal of the Iranian Chemical Society
Fig. 14 FT-IR of recovered catalyst
Acknowledgements The authors would like to highly appreciate the
experimental facilities provided by Ahvaz Branch, Islamic Azad Uni-
versity, Ahvaz, Iran.
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