Efficient synthesis of spirooxindole derivatives by magnetic and recyclable CaFe2O4@MgAl-LDH

Article abstract of DOI:10.1007/s13738-020-02017-7

A promising chemotherapeutic agent is spirooxindole. Probable targets involve cancers of the lung, liver, breast, colon, stomach, and prostate. Widespread drug discovery applications and biological activity are significant synthetic targets of spirooxindo

Full text of DOI:10.1007/s13738-020-02017-7

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-020-02017-7
SHORT COMMUNICATION
Efcient synthesis of spirooxindole derivatives by magnetic
and recyclable CaFe2O4@MgAl‑LDH
Mehri Salimi1 · Reza Sandaroos1 · Farzaneh Esmaeli‑nasrabadi1
Received: 17 March 2020 / Accepted: 22 July 2020
© Iranian Chemical Society 2020
Abstract
A promising chemotherapeutic agent is spirooxindole. Probable targets involve cancers of the lung, liver, breast, colon,
stomach, and prostate. Widespread drug discovery applications and biological activity are signifcant synthetic targets of
spirooxindoles. In the present study, the synthesis of CaFe2O4 nanoparticles via the sol–gel method is discussed. Vibrating
sample magnetometer, scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray difraction were
used to prepare and characterize CaFe2O4@MgAl-LDH as an efective catalyst for the preparation of spirooxindole deriva-
tives via one-pot, the three-component reaction of malononitrile, CH-acids (1,3-dicarbonyl compounds), and isatin in the
presence of CaFe2O4@MgAl-LDH in excellent yields with short reaction times in aqueous media is used to describe a facile
and efcient multicomponent synthesis of functionalized spirooxindoles.
Keywords Malononitrile · Spirooxindoles · Multicomponent reaction · 1,3-Dicarbonyl compounds · CaFe2O4@MgAl-LDH
Introduction
and deoxidization, gas absorbers, high-temperature sensors,
and oxidation [10], oxidation catalysts, gas absorbers, among
others [11, 12]. The co-precipitation [13], sol–gel, hydro-
thermal [14], and aerosolization methods [15], auto com-
bustion [16] can be used to produce magnetic nanoparticles.
It is favorable to use 2D materials as catalyst supports
[17] because they have exceptional mechanical robustness
and excellent electronic properties. Layered double hydrox-
ide (LDH) is a kind of 2D material, and its advantages
include low cost, exclusive structure, easy preparation, high
stability, and composition diversity. It has presented count-
less potential in the synthesis and design of new supported
catalysts.
In a variety of applications such as biomedical applications
[1], magnetic fuids [2], and catalyst [3], the magnetic nano-
particles have been mainly used. The shape and size of metal
nanoparticles infuence the magnetic properties of them [4].
Nowadays, wide applications of magnetic oxide nanoparti-
cles, both in fundamental research and industrial use, have
made signifcant interest [5]. Because of their interesting
magnetic, optical, and catalytic properties, CaFe2O4 NPs are
among several kinds of nanoparticles that are presently get-
ting a lot of interest [6, 7]. Because of the presence of Ca2+
rather than heavy metals, calcium ferrite, among well-known
other ferrites, for example, ZnFe2O4, NiFe2O4, MnFe2O4,
CuFe2O4, and CoFe2O4, has an important beneft as it is
eco-friendly and biocompatible [8]. Also, due to chemical
stability and biocompatibility, these particles are potentially
benefcial for a wide range of applications [9].
Due to their frequent presence in many synthetic and
natural products along with valuable biological activities,
oxindoles play a signifcant role in the area of heterocyclic
chemistry. In natural compounds and biological activities
including anti-infammatory activities, antiprotozoal, pro-
gesterone receptors (PR) agonists, and antibacterial, oxin-
dole derivatives often appear as signifcant structural com-
ponents [18–21].
Calcium- and iron-based compounds have been studied
for possible uses in optical memory tools as well as the pro-
duction of steel through dephosphorization, desulfuration,
It has been recently reported in the literature that several
procedures of this strategy include reaction of dimedone,
isatin, and malononitrile in the presence of GN/SO3H [22],
CoFe2O4@SiO2 [23], Borax [24], sodium stearate [25], Al-
ITQ-HB [26], Alum [27], TEBA [28], CoFe2O4@SiO2@
* Mehri Salimi
msalimi@birjand.ac.ir; m_salimi4816@yahoo.com
1
Department of Chemistry, Faculty of Science, University
of Birjand, P. O. Box 97175-615 Birjand, Iran
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
Co(III) Salen complex [29], DES [30], NEt3 [31], SBA-PR-
NH2 [32], and Ni NPS [33].
which were reported in cm−1. A Bruker DPX-250 Avance
1
instrument was used to measure HNMR and 13CNMR
In this work, our research continues on developing envi-
ronmentally friendly organic synthesis, especially with
nanocatalyst [34–44]. CaFe2O4@ MgAl-LDHs was intro-
duced as an active, recyclable, and efective magnetic nano-
catalyst. This nanocatalyst can be used for various organic
functional group transformations in green processes. Then,
its catalytic efciency in the preparation of spirooxindoles
was investigated by the coupling of malononitrile and vari-
ous isatins with 1,3-dicarbonyl. High to excellent yield and
selectivity of the corresponding delivered products were
found. Unique advantages including simple synthesis of
the catalyst, high magnetic property, and easy separation
of the catalyst with a permanent magnet, the application of
available and inexpensive precursors are also presented in
this study. Also, under the applied reaction conditions, the
catalytic systems exhibited high reusability and durability.
The stability, reusability, and reactivity of the catalyst were
also enhanced against the reaction processes (Scheme 1).
spectra at 250 MHz and 62.9 MHz in CDCl3 or DMSO-d6.
The chemical shift was given in ppm relative to TMS as
the internal standard. A Bruker D8-advance X-ray difrac-
tometer with Cu Kα (λ = 0.154 nm) radiation was used to
carry out power X-ray difraction (XRD). Using vibrating
sample magnetometer (VSM) leak shore 7200, the mag-
netic properties were determined at 300 K Vsm leak shore.
MIRA 3TESCAN-XMU spectrometer was used for scan-
ning electron microscopy.
Catalyst preparation
Preparation of CaFe2O4 nanoparticles
The conventional sol–gel method was used to synthe-
size the calcium ferrite nanoparticles. A mixture of
1 M solution of Ca(NO3)2·6H2O and 2 M solution of
Fe(NO3)3·9H2O was prepared. 2.5 M citric acid solution
along with 7 ml of ethylene glycol was added to this mix-
ture. The constantly magnetically stirring was done, and
heating was carried out at 80–90 °C. Heat treatment is
also signifcant for drying gel, and fnally, the powder was
prepared. Ethanol was used to wash the obtained powder
thoroughly. In a vacuum oven, it was dried overnight at
60 °C. At 550 °C, the obtained product was calcined for
3 h [45].
Experimental
Chemicals
Reagents and solvents were produced in Merck or Fluka
chemical companies. An Electrothermal 9100 apparatus
was used to measure melting points. A PerkinElmer 781
spectrometer was used to take IR spectra in KBr pellets,
Scheme 1 Preparation of
spirooxindole derivatives with
CaFe2O4@ MgAl-LDHs nano-
particle
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Journal of the Iranian Chemical Society
Preparation of CaFe2O4@ MgAl‑LDHs nanoparticles
2‑Amino‑7,7‑dimethyl‑2′,5‑dioxo‑5,6,7,8‑tetrahydrosp
iro [chromene‑4,3′‑indoline]‑3‑carbonitrile (Compound
11, Table 1): White solid, mp>250 °C. 1HNMR (250 MHz,
DMSO-d6) 1.02 (3H, s, CH3), 1.12 (3H, s, CH3), 2.07-2.12
(2H, m, CH2), 2.54 (2H, m, CH2), 6.68 (d,1H, J 7.3 Hz,
Ph), 6.88 (t, 1H, J 7.3 Hz, Ph), 7.08 (d, 1H, J 7.3 Hz, Ph),
7.23 (t, 1H, J 7.4 Hz, Ph), 7.31 (s, 2H, NH2), 10.64 (s, 1H,
NH). 13CNMR(62.9 MHz, DMSO-d6) 195.2 (C=O), 178.4
(C=O), 166.5 (C), 159.1 (C), 152.3 (C), 142.4 (C), 134.8
(CH), 128.5 (CH), 123.3 (CH), 122.1 (CH), 117.7 (C), 112.2
(C ≡ N), 109.6 (C), 57.9 (C), 50.4 (CH2), 47.2 (C), 32.3
(CH2), 28.0 (CH3), 27.0 (CH3). IR (KBr, cm−1): 3374, 3311,
The CaFe2O4 particles of 0.50 g were dispersed in deionized
water and methanol (80 ml) with a deionized water/metha-
nol molar ratio of 1:1 by an ultrasonic cleaner. CaFe2O4
was created in the form of a suspension in 15 min (solu-
tion A). To obtain a metal nitrate solution, Al(NO3)3·6H2O
of 1.13 g and Mg(NO3)2·6H2O of 1.96 g were dissolved in
100 ml of deionized water (solution B). NaOH of 0.39 g
and Na2CO3 of 2.12 g were dissolved in 100 ml of deion-
ized water (solution C). At room temperature, solution B
was dropped into solution A along with solution C until pH
to 10 under vigorous stirring. Then, for 24 h, the mixture
was heated to 65 °C. Finally, using a magnet, the resulting
products were separated and later, washed with ethanol and
deionized water several times. Then, to obtain the magnetic
precursor CaFe2O4@MgAl-LDHs, the formed products were
dried at 65 °C in a forced air oven for 12 h [46].
3143, 2927, 2194, 1723, 1654, 1349, 1225, 1055 cm−1
.
Anal. Calcd for C19H17N3O3: C, 68.05; H, 5.11; N, 12.53%.
Found: C, 67.86; H, 5.14; N, 12.65%.
Results and discussion
Catalytic activity
From Fe(NO3)3·9H2O and Ca(NO3)2·6H2O, CaFe2O4 was
synthesized. Then, in methanol/deionized water, an appro-
priate amount of CaFe2O4 nanoparticles was dispersed.
Then, to obtain a metal nitrate solution, Al(NO3)3·6H2O
and Mg(NO3)2·6H2O were dissolved in 100 ml of deionized
water. In 100 ml of deionized water, NaOH and Na2CO3
were dissolved. Then, the solution of Al(NO3)3·6H2O,
Mg(NO3)2·6H2O, NaOH, and Na2CO3 was dropped to
achieved CoFe2O4@MgAl-LDHs (corresponding hetero-
geneous CaFe2O4@ MgAl-LDHs, Scheme 2).
General procedure for the preparation of spirooxindole
derivatives
CaFe2O4@MgAl-LDHs of 0.002 g was added to a mixture
of 1.0 mmol of 1,3-dicarbonyl compounds, 1.0 mmol of
isatin, and 1.0 mmol of malononitrile in water as a solvent.
◦
At 70 C, the mixture was stirred for appropriated reaction
time. TLC was used to monitor the progress of the reaction.
When the reaction was completed, the mixture was dissolved
in ethyl acetate, and an external magnet was used to separate
the CaFe2O4@MgAl-LDHs. Then, under reduced pressure,
the solvent was removed from the solution. Using ethanol,
the resulting product was purifed by recrystallization to
obtain the pure spirooxindole product in excellent purity and
yield. 1HNMR, 13CNMR, and IR spectra of the products are
bases of their structural assignments.
Scanning electron microscopy (SEM), vibrating sample
magnetometer (VSM), Fourier transform infrared (FTIR)
analyses, and powder X-ray difractometry (XRD) were used
to characterize the catalyst.
Catalyst characterization
FTIR spectroscopy
Selectedspectraldata 2‑Amino‑2′,5‑dioxo‑5,6,7,8‑tetrahy
drospiro‑[chromene‑4,3′‑indoline]‑3‑carbonitr
ile (Compound 6, Table 1): White solid, mp>250 °C.
1HNMR (250 MHz, DMSO-d6) 1.91 (2H, m, CH2), 2.14
(2H, m, CH2), 2.59 (2H, m, CH2), 6.65 (d,1H, J 7.39 Hz,
Ph), 6.87 (t, 1H, J 7.39 Hz, Ph), 7.11 (d, 1H, J 7.39 Hz, Ph),
7.21 (t, 1H, J 7.39 Hz, Ph), 7.37 (s, 2H, NH2), 10.66 (s, 1H,
NH). 13CNMR (62.9 MHz, DMSO-d6) 195.1 (C=O), 178.2
(C=O), 166.1 (C), 158.7 (C), 142.1 (C), 134.5 (C), 128.5
(CH), 123.3 (CH), 121.8 (CH), 117.4 (CH), 112.9 (C ≡ N),
109.2 (C), 57.6 (C), 46.9 (C), 36.4 (CH2), 26.8 (CH2), 19.8
(CH2). IR (KBr, cm−1) 3354, 3296, 3174, 2952, 2204, 1712,
1655, 1350, 1214, 1075. Anal. Calcd for C17H13N3O3: C,
66.44; H, 4.26; N, 13.67%. Found: C, 66.42; H, 4.31; N,
13.72%.
FTIR spectroscopy was used to study the FTIR at 4000 to
400 cm−1 for (a) CaFe2O4 and (b) CaFe2O4@ MgAl-LDHs;
the results are shown in Fig. 1. Due to O–H stretching and
bending vibrations, the FTIR spectra of calcium ferrite nano-
particles, Fig. 1a exhibits abroad stretch at 3419 cm−1 cm−1.
Metal–alloy (Fe–Ca) corresponds to the band at 1094 cm−1,
and due to the presence of ferrite skeleton, bands at 634 and
585 cm−1 are attributed to Fe–O bonds [47].
In spectrum 1b, the broad bands which were displayed in
the range of 3130–3627 cm−1 were assigned to OH group
stretching, and the absorption band, which was around
1630 cm−1, was caused by the fexural oscillation peaks of
interlayer water molecules [48]. Also, the absorption peaks
around 1384 cm−1 were considered to be caused by the
asymmetric stretching bond of intercalated NO2− [49]. This
3
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Journal of the Iranian Chemical Society
Table 1 Synthesis of spirooxindole derivatives
Substrate
3
Time
(min)
Yield
(%)
Entry
Product
Substrate 1
O
Substrate 2
H2N
NC
O
OH
CN
CN
O
O
1
4
4
96
97
N
H
O
O
O
O
O
N
H
O
OH
H2N
NC
O
F
CN
CN
O
O
2
F
N
H
O
O
N
H
O
O
OH
H2N
NC
O
H3C
CN
CN
O
O
3
4
5
5
96
95
H3C
N
O
O
N
H
O
O
O
H
O
OH
H2N
NC
O
Br
CN
CN
O
O
Br
N
O
O
N
CH3
O
CH3
O
OH
H2N
NC
O
Cl
CN
CN
O
O
5
6
10
82
96
Cl
N
O
O
N
O
O
CH2Ph
CH2Ph
H2N
NC
O
O
O
CN
CN
O
6
O
N
H
O
N
H
O
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Journal of the Iranian Chemical Society
Table 1 (continued)
Substrate
3
Time
(min)
Yield
(%)
Entry
Product
Substrate 1
Substrate 2
O
O
H2N
NC
O
H3C
CN
CN
H3C
O
7
5
5
97
94
81
O
N
O
N
H
O
H
H2N
O
O
O
NC
Br
CN
CN
Br
Cl
O
8
9
O
N
O
O
N
CH3
O
CH3
H2N
NC
O
O
O
Cl
F
CN
CN
O
12
O
N
N
CH2Ph
O
CH2Ph
H2N
NC
O
O
O
CN
CN
F
O
10
11
5
4
96
96
O
N
O
N
H
O
H
O
H2N
NC
O
O
CH3
CH3
CN
CN
O
H3C
H3C
O
N
O
N
H
O
H
O
O
H2N
NC
O
F
CH3
CH3
CN
CN
F
O
12
4
97
H3C
H3C
O
O
N
H
N
H
O
indicates the presence of a small number of carbonate ions
in the LDH phase. Al–OH stretching may be responsible for
the bond at 646, 710, and 1160 cm−1 [50]. The lattice vibra-
tion of metal–oxygen bonds (M–O) was responsible for the
absorption peaks around 550–770 cm−1.
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Journal of the Iranian Chemical Society
Table 1 (continued)
Substrate
3
Time
(min)
Yield
(%)
Entry
Product
Substrate 1
Substrate 2
O
H2N
NC
O
O
H3C
CH3
CH3
CN
CN
H3C
O
13
5
5
96
95
81
H3C
H3C
O
N
O
N
H
O
O
O
H
O
O
O
H2N
NC
O
Br
CN
CN
CH3
CH3
Br
O
14
H3C
H3C
O
O
N
N
CH3
CH3
O
H2N
NC
O
N
Cl
CN
CN
CH3
CH3
Cl
O
15
12
H3C
H3C
O
O
N
CH2Ph
CH2Ph
Scheme 2 Preparation of CaFe2O4@ MgAl-LDHs
X‑ray difraction (XRD) analysis
In the case of CaFe2O4 (Fig. 2a), the most prominent
peaks present at 23.41°, 30.33°, 32.40°, 38.47°, and
48.87° which are corresponding to the (2 1 0), (21 2),
(2 0 2), (2 0 3) and (4 0 2) planes of CaFe2O4, respec-
tively. Thus, the sample is identified as orthorhombic
CaFe2O4 corresponding to reported data (DB card num-
ber 9013281). There are also peaks present at 43.01°
and 78.24°, which are corresponding to the (133) and
(0 8 3) planes of CaFe5O7, which indicates the complex
nature of the sample. Typically, an intergrowth between
By the prominent use of XRD measurement, crystalline
structures of the CaFe2O4 particles could be clearly under-
stood. The crystalline nature of the samples is determined
by the sharp peaks from difraction patterns. As shown in
Fig. 2, the good match of the XRD pattern of the synthesized
calcium ferrite powder with the documented XRD data of
CaFe2O4 (JCPDS card No. 32-0168) indicated that well-
crystallized catalyst had been obtained.
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Journal of the Iranian Chemical Society
Fig. 2 XRD results of a CaFe2O4, b CaFe2O4@ MgAl-LDHs
Fig. 1 FTIR spectra for the a CaFe2O4, b CaFe2O4@ MgAl-LDHs
one CaFe2O4 unit and 3 units of FeO wustite-type struc-
tures forms CaFe5O7 [51]. This is common for CaFe2O4
because it naturally exists as a system comprising the
different oxidation states of Fe.
The characteristic diffraction peaks of a well-crys-
tallized LDH phase (JCPDS NO. 22-0452) were pre-
sented by MgAl-LDH at 2θ of 11.71°, 34.33°, 61.34°,
and 62.68°, corresponding to the reflections of planes
(001), (100), (110), and (111), respectively. The success-
ful synthesis of the LDH was determined by the diffrac-
tion peaks.
Vibrating sample magnetometer (VSM)
By a vibrating sample magnetometer (VSM), the magnetic
properties of CaFe2O4 and CaFe2O4@ MgAl-LDHs nano-
particles were studied at 300 K (Fig. 3). For CaFe2O4@
MgAl-LDHs nanoparticles, the saturation magnetization
value decreased compared to the CaFe2O4.
Fig. 3 VSM pattern of CaFe2O4 and CaFe2O4@MgAl-LDH
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Journal of the Iranian Chemical Society
Yield (%)
Time (min)
Scanning electron microscopy (SEM)
5
Solvent free
Acetonitrile
DMSO
The size and morphology information of CaFe2O4 nanoparti-
cle is provided by SEM analysis of the products (Fig. 4). The
results presented that the average product size of CaFe2O4
nanoparticle was 26.36–57.76 nm.
15
15
60
95
90
90
97
12
10
EtOH
The catalytic activity of CaFe2O4@MgAl‑LDHs
for the synthesis of spirooxindoles
H2O + EtOH
H2O
6
4
For the first time, CaFe2O4@MgAl-LDHs was used as
an efcient and recyclable nanocatalyst for the synthesis
of spirooxindoles by the coupling of various isatins with
1,3-dicarbonyls and malononitrile to show the merit of
synthesized nanocatalyst in organic reactions. The model
substrates were isatins, dimedone, and malononitrile. The
reaction was examined in various solvents (Fig. 5). The
results indicate that the efciency of the reaction is afected
by diferent solvents. Low yield (60%) was aforded by ace-
tonitrile, while the yields could be improved using solvents
such as water, ethanol, and DMSO. Finally, using water as a
solvent, the yield increased to 97%, which is better than any
other solvents examined here. The yield of model reaction
decreased to 5% in the absence of solvent.
0
20
40
EtOH
90
60
DMSO
95
80
100
H2O
97
4
H2O + EtOH
90
Acetonitrile Solvent free
Yield (%)
Time (min)
60
15
5
15
6
10
12
Fig. 5 The efect of several solvents in the preparation of spiroox-
indole by CaFe2O4@MgAl-LDHs. Reaction conditions: dimedone
(1.0 mmol), isatin (1.0 mmol), and malononitrile (1 mmol), at 70 °C,
0.002 g CaFe2O4@MgAl-LDHs
character of the methylene carbon (C-2) of dimedone. Thus,
it helps to increase the reaction rate [30].
The amount of catalyst was also changed. Figure 6 sum-
marizes the results. The results presented that the catalyst
concentration reaction afects the yield crucially. Under
the same conditions, decreasing the catalyst concentration
resulted in lower yields. The product signifcantly reduced,
with catalyst concentration increasing (more 0.002 g). Con-
sequently, because the reaction was completed within high
A fundamental strategy for constructing MCRs is the
electrophilic reaction of isatin with two diferent nucleo-
philes, water, and protic solvent which helps in the enoliza-
tion of dimedone as well as its action as a solvent by making
hydrogen bonds with the OH. This increases the nucleophilic
Fig. 4 SEM images of CaFe2O4
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Journal of the Iranian Chemical Society
Yield (%)
Time (min)
Yield (%)
Time (min)
Amount of Catalyst (g)
97
97
100
6
5
4
3
2
1
3
6
4
3
2
1
0.004
90
5
4
97
0.002
4
90
60
15
20
3
0.001
45
6
0
2
30
40
1
0
40
2
60
80
100
0
20
40
60
80
100
1
6
3
97
4
4
97
3
1
2
45
2
3
60
3
4
97
4
5
90
5
6
100
6
Yield (%)
Time (min)
Amount of Catalyst (g)
90
15
0.001
Yield (%)
Time (min)
40
30
0
1
0.002
0.004
Fig. 8 The efect of diferent time in the preparation of spirooxin-
dole by CaFe2O4@MgAl-LDHs. Reaction conditions: dimedone
(1.0 mmol), isatin (1.0 mmol), and malononitrile (1 mmol) in H2O
(0.5 cc), 70 °C
Fig. 6 The efect of diverse catalysts in the preparation of spiroox-
indole by CaFe2O4@MgAl-LDHs. Reaction conditions: dimedone
(1.0 mmol), isatin (1.0 mmol), and malononitrile (1 mmol) in H2O
(0.5 cc), at 70 °C
yield, this condensation was best catalyzed by 0.002 g of
CaFe2O4@MgAl-LDHs. The reaction was performed in the
presence of CaFe2O4 and efciency was 20%.
catalyst within 4 min in H2O as a solvent, spirooxindole
was achieved with an excellent yield (97%).
Evaluation using various 1,3-dicarbonyl and isatin com-
pounds was carried out to explore further the scope and
limitation of this protocol under the optimized conditions,
particularly regarding library construction. Table 1 sum-
marizes the results. In all cases, to aford the correspond-
ing spirooxindoles in good to excellent yields (81–97%) in
short reaction times, the reaction proceeded readily.
In comparison with most of the reported works, this
catalyst showed good catalytic activity and good yields
(97%) in shorter times (see Table 2).
By carrying out the model reaction at diferent tempera-
tures, the efect of the temperature of the reaction was stud-
ied. The best result was obtained within 70 °C (Fig. 7).
By carrying out the model reaction at various times, the
efect of time of reaction was investigated. The best outcome
was obtained within 4 min (Fig. 8).
This coupling was carried out in the absence of cata-
lysts to study the catalytic activity of CaFe2O4@MgAl-
LDHs. In this case, over model reaction time, the reac-
tion proceeded in low yield (6%). Using 0.002 g of the
Herein, in Scheme 3, a mechanism was proposed for the
CaFe2O4@MgAl-LDHs catalyzed preparation of spiroox-
indole. Thus, it is demonstrated that the CaFe2O4@MgAl-
LDHs induces the polarization of the carbonyl group of
isatin, which is followed by the nucleophilic addition of
malononitrile to isatin. Then, this intermediate subse-
quently undergoes elimination via Knoevenagel conden-
sation. The spirooxindole derivatives are aforded by the
addition of dimedone to intermediate [29].
Yield (%)
Time (min)
T (oC)
95
95
3
4
3
2
1
80
4
70
90
A permanent external magnet could recover the cata-
lyst at the end of the reaction. Ethanol was used to wash
the recycled catalyst, which is then subjected to a second
reaction process. According to the results, the yield of the
product was only slightly reduced after fve runs (Fig. 9).
After fve runs, the reused catalyst characterization (FTIR
spectra (Fig. 10)) was obtained where no important vari-
ation was seen in the structure of the recovered catalyst
with the fresh catalyst.
15
60
60
0
25
0
20
40
2
60
80
100
1
0
3
95
4
Yield (%)
Time (min)
T (oC)
90
95
60
25
15
60
4
70
3
80
Fig. 7 The efect of diferent temperatures in the preparation of
spirooxindole by CaFe2O4@MgAl-LDHs. Reaction conditions: dime-
done (1.0 mmol), isatin (1.0 mmol), and malononitrile (1 mmol) in
H2O (0.5 cc)
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Journal of the Iranian Chemical Society
Table 2 Comparison of results
utilizing CaFe2O4@MgAl-
LDHs with diferent catalysts
Entry
Catalyst
Solvent/T (oC)
Time (min)
Yield (%)
References
1
2
3
4
5
6
GN/SO3H
Borax (10 mol%)
(SB-DBU)Cl
SBA-PR-NH2
β-Cyclodextrin
CaFe2O4@MgAl-LDH
EtOH/water (1:1)/ref.
EtOH/ref.
EtOH/r.t
H2O/ref.
H2O/60 °C
H2O/70 °C
40
120
150
5
480
4
95
94
97
80
88
97
[22]
[24]
[52]
[32]
[53]
This work
Malononitrile (1 mmol), isatin (1 mmol), dimedone (1 mmol)
Scheme 3 An acceptable mechanism for the synthesis of spirooxindole with CaFe2O4@MgAl-LDHs
of efciency, the catalyst was recycled for at least fve
consecutive runs. The advantages of the catalyst include
the performance, preparation from cheap and accessible
materials, environmentally benign nature, and cost-efec-
tiveness. These advantages make it a suitable alternative
for the preparation of spirooxindole. Moreover, separation
and recovery of the catalyst for another catalytic recycling
are easy.
Conclusion
In conclusion, using CaFe2O4@MgAl-LDHs, a facile
methodology was developed to prepare spirooxindole
derivative nanoparticles as an efficient heterogeneous
catalyst. At 70 °C, the catalyst represents an outstanding
activity in water. For a wide variety of substrates, a good
to high yield of products was obtained within short reac-
tion times. FTIR, SEM, VSM, and XRD analyses were
used to characterize the catalyst. With the negligible loss
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Journal of the Iranian Chemical Society
Yield (%) Runs
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