A comparative study on the catalytic activity of Fe3O4@SiO2–SO3H and Fe3O4@SiO2–NH2 nanoparticles for the synthesis of spiro [chromeno [2, 3-c] pyrazole-4, 3′-indoline

Article abstract of DOI:10.1007/s11164-016-2470-6

Abstract: Sulfuric acid and (3-aminopropyl)-triethoxysilane were successfully attached to the core–shell structure of Fe₃O₄@SiO₂ nanoparticles separately. The prepared nanoparticles were characterized by vibrating sample m

Full text of DOI:10.1007/s11164-016-2470-6

Res Chem Intermed
DOI 10.1007/s11164-016-2470-6
A comparative study on the catalytic activity
of Fe3O4@SiO2–SO3H and Fe3O4@SiO2–NH2
nanoparticles for the synthesis of spiro [chromeno
[2, 3-c] pyrazole-4, 30-indoline]-diones under mild
conditions
Fatemeh Alemi-Tameh1 Javad Safaei-Ghomi1
•
•
Mohammad Mahmoudi-Hashemi1
•
Raheleh Teymuri2
Received: 14 January 2016 / Accepted: 1 February 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract Sulfuric acid and (3-aminopropyl)-triethoxysilane were successfully attached
to the core–shell structure of Fe3O4@SiO2 nanoparticles separately. The prepared
nanoparticles were characterized by vibrating sample magnetometer, powder X-ray
diffraction, scanning electronic microscopy, thermal gravimetric analysis, energy disper-
sive X-ray spectroscopy, and Fourier transform infrared spectroscopy. To compare the
efficiency of the two prepared functionalized magnetic nanoparticles, they were employed
as catalysts for the synthesis of spirooxindole containing chromene ring fragments in one-
pot four-component reactions. Sulfuric acid-functionalized magnetic nanoparticles showed
high catalytic activity in mild reaction conditions and short reaction times and excellent
yields of products. The catalyst was easily separated using a magnet and reused for several
cycles of reactions without any significant loss of catalytic activity.
&
Javad Safaei-Ghomi
safaei@kashanu.ac.ir
1
2
Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran,
I. R. Iran
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan 51167,
I. R. Iran
123

F. Alemi-Tameh et al.
Graphical Abstract
Keywords Fe3O4@SiO2–SO3H NPs Á Spirooxindoles Á Multicomponent reactions Á
One-pot synthesis Á Core–shell
Introduction
Following the principles of green chemistry, using recyclable solid catalysts in organic
reactions has attracted much attention in recent years [1]. Among different solid
catalysts, supported magnetic nanoparticles (MNPs) are more interesting and widely
used in organic reactions [2]. MNPs have especially attracted great attention due to their
extensive range of usages in different fields such as drug delivery [3], magnetic
resonance imaging (MRI) [4], cancer treatment through hyperthermia [5], and
absorption of heavy metals from aqueous solutions [6]. The significant properties of
Fe3O4-based nanocatalysts include high stability, easy preparation, high catalyst
loading, and simple catalyst recycling. In addition, surface functionalization of MNPs is
an effective way to createa link between the feature of homogeneous and heterogeneous
catalysis [7, 8]. Recently, MNPs have been used as an efficient heterogeneous
nanocatalyst in a number of organic reactions such as Buchwald–Hartwig, Suzuki [9],
Sonogashira–Hagihara [10], and Paal–Knorr [11, 12] reactions, synthesis of sulfon-
amides [13], coupling of phenols with aryl halides [14], and synthesis of a-aminonitriles
and imines [15].
Multicomponent reactions (MCRs) are regarded as economic methods for the
construction of novel complex molecules in a single step procedure. High atom
economy, short reaction times, high selectivity, minimized waste, and avoidance of
costly purification processes are the characteristics of MCRs [16, 17]. Using these
procedures provide a significant route to produce biologically active compounds [18,
123

A comparative study on the catalytic activity…
F
Cl
O
NH
N
Cl
Et
MeO
Cl
NH
O
O
O
O
N
H
N
H
N
H
HO
Cl
N
H
Horsflline
Elacomine
NITD609
MDM2-P53
Fig. 1 Some biologically important molecules containing spirooxindole motif
19]. The indole nucleus is a renowned heterocyclic unit in a variety of pharmaco-
logical agents [20]. Moreover, it has been reported that sharing of indole C-3 in the
creation of spiroindolines greatly improved its biological property [21–24]. The
spirooxindole system is the core structure of many biologically active molecules such
as NITD609 and MDM2-P53 [25], Elacomine and Horsfline (Fig. 1) [26].
Because of their extensive biological activities, producing novel spirooxindole
derivatives is an interesting subject in medicinal chemistry. Recently, several
attempts have also been made for the construction of spirooxindoles via one-pot
four-component reactions of isatin, hydrazine hydrate, ethyl acetoacetate, and a
compound with an acidic a-hydrogen such as dimedone or malononitrile in the
presence of an acid catalyst such as p-toluene sulfonic acid [27] or a base catalyst
such as 4-dimethylaminopyridine (4-DMAP) [28], meglumine [29], piperidine [30],
L-proline, and a silica-supported organocatalyst system based on L-proline (SSLP)
[31]. Although all reports have their own merits, some of these methods have certain
drawbacks such as use of toxic, non-reusable, and expensive catalysts, consumption
of large amounts of catalyst, long reaction times and high temperatures. Therefore,
continuing research to find economical procedures seems to be necessary. In this
paper we decided to report an efficient and green method for the synthesis of spiro
[chromeno [2, 3-c] pyrazole-4, 30-indoline]-diones via one-pot two-step four-
component reaction of isatin, hydrazine hydrate, ethyl acetoacetate, and dimedone
or 1, 3-cyclohexadione. Also, we compared sulfuric acid functionalized magnetic
nanoparticles and amino functionalized magnetic nanoparticles as acid and base
catalysts to promote the yields and rates of this reaction (Scheme 1).
Experimental
All materials were purchased from Sigma–Aldrich and Merck and were used without
further purification. All melting points were determined in capillary tubes on a
Boetius melting point microscope. 1H NMR and 13C NMR spectra were recorded on
Bruker Avance-400 MHz spectrometer using DMSO-d6 as solvent. The elemental
analyses (C, H, and N) were obtained by means of a Carlo ERBA Model EA 1108
analyzer. Fourier transform infrared (FTIR) spectra were recorded on WQF-510,
spectrometer 550 Nicolet in the range of 400–4000 cm-1 using KBr pellets. The
energy-dispersive X-ray spectroscopy (EDS) measurements were performed by
123

F. Alemi-Tameh et al.
R1
N
R1HN NH2
N
O
O
O
O
X
1
Fe3O4 @SiO2 -SO3H
EtOH
X
+
+
R
O
O
O
N
O
O
R
OEt
R
R
H
3
N
H
4
2
5a-j
R1= Ph, H
X = H, Cl, Br, NO2
R = Me, H
Scheme 1 One-pot four-component reaction for the synthesis spiro [chromeno [2, 3-c] pyrazole-4,
30-indoline]-diones derivatives
SAMX analyzer. Powder X-ray diffraction (XRD) measurements were carried out on
a Philips diffractometer of X’pert Company with monochromatized Cu Ka radiation
(k = 1.54056 nm). A TGAQ5 thermogravimetric analyzer was used to study the
thermal properties of the compounds under an inert N2 atmosphere at 20 mL min-1
and heating rate of 10 °C min-1. SEM images were taken by MIRA3-TESCAN. The
magnetic properties of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2–NH2 , and Fe3O4@
SiO2–SO3H nanoparticles were measured with a vibrating sample magnetometer
(VSM, PPMS-9T) at 300 K in Kashan University, Iran.
Preparation of Fe3O4 nanoparticles
Fe3O4 nanoparticles were synthesized by co-precipitation. FeCl3Á6H2O (11.68 g)
and FeCl2Á4H2O (4.30 g) were dissolved in 200 mL deionized water, then 15 mL
NH3ÁH2O (25 %) was added to the solution drop wise under nitrogen atmosphere
and vigorous stirring at 70–75 °C. The magnetic nanoparticles were separated from
solution by using an external magnet and washed twice with deionized water.
Preparation of Fe3O4@SiO2 nanoparticles
One gram of magnetic nanoparticles was dispersed in 20 mL ethanol in ultrasonic
bath and sonicated for 30 min at room temperature. Then, 6 mL aqueous NH3
(25 %) and 2 ml tetraethyl orthosilicate (TEOS) were added to the solution. The
resulting solution was stirred at 35–40 °C for 24 h. The Fe3O4@SiO2 NPs were
separated from solution by using an external magnet and washed with ethanol
(3 9 15 mL) and dried at room temperature.
Preparation of Fe3O4@SiO2–NH2 nanoparticles
One gram of Fe3O4@SiO2 nanoparticles was dispersed in 25 mL of dry toluene and
sonicated for 15 min. Then, 2.2 mL 3-(aminopropyl)-triethoxysilane (APTES) was
added to the solution drop wise and the mixture was refluxed under nitrogen
atmosphere with vigorous stirring for 20 h. Finally, Fe3O4@SiO2–NH2 nanoparticles
123

A comparative study on the catalytic activity…
were separated from solution by using a magnet and washed several times with
20 mL ethanol and dried at room temperature. The APTES content in Fe3O4@SiO2
NPs is 2.84 mmol/g which agrees well with the content of nitrogen element in
Fe3O4@SiO2–NH2 NPs evaluated by elemental analysis.
Preparation of Fe3O4@SiO2–SO3H nanoparticles
Firstly, 1 g of Fe3O4@SiO2 was dispersed in dry CH2Cl2 (16 mL) and sonicated for
10 min. Then, chlorosulfonic acid (0.8 mL in dry CH2Cl2) was added drop-wise to a
cooled (ice-bath) solution of Fe3O4@SiO2, during a period of 30 min under
vigorous stirring. The mixture was stirred for 60 min, while the residual HCl was
removed by suction. The resulted MNPs were separated by using a magnet, washed
several times with dried CH2Cl2 and methanol before being dried under vacuum at
60 °C. The number of H? sites of Fe3O4@SiO2–SO3H NPs was determined by pH-
ISE conductivity titration (Denver Instrument Model 270) and found to be 1.69 H?
sites per 1 g of solid acid at 25 °C. The overall schematic procedure used to
synthesize the magnetic nanocatalysis is illustrated in Scheme 2.
OH
HO
HO
HO
OH
OH
Fe Cl3, 6H2O
NH4OH
TEOS
D.I. water,75°C
NH4OH
+
Fe Cl2, 4H2O
Fe3O4
HO
OH
OH
OH
Fe3O4 @SiO2
OH
OH
HO
HO
C
l
S
O
H,
d
S
E
r
y
C
T
P
H
A
OH
.
C
l
2
N
1
,
x
OH
u
l
f
e
r
.
2
SO3H
SO3H
NH2
NH2
O
Si
O
O
O
O
Si
O
O
O
O
SO3H
O
SO3H
O
O
O
O
O
Si
O
Si
O
O
SO3H
NH2
SO3H
NH2
Fe3O4@SiO2-NH2
Fe3O4@SiO2-SO3H
Scheme 2 Preparation routes of Fe3O4@SiO2–NH2 and Fe3O4@SiO2–SO3H nanoparticles
123

F. Alemi-Tameh et al.
General procedure for the Fe3O4@SiO2–SO3H NPs catalyzed
multicomponent synthesis of spiro [chromeno [2, 3-c] pyrazole-4,
30-indoline]-diones derivatives (5a–j)
A mixture of hydrazine hydrate 1 (1.1 mmol), ethyl acetoacetate 2 (1.1 mmol), isatin
3 (1 mmol), and Fe3O4@SiO2–SO3H (0.02 g) nanoparticles was heated in EtOH
(10 mL) at 80 °C for 5 min. Then, dimedone 4 (1 mmol) was added to the above
mixture, and the mixture was heated for 25 min. The completion of the reaction was
monitored by TLC, and the catalyst was separated from reaction by an external
magnet before work-up. Then the mixture was poured into cold water and the
obtained precipitate was filtered and recrystallized twice in EtOAc/n-hexane (3:1).
Spectral data of products
3, 7, 7-Trimethyl-7, 8-dihydro-1H-spiro [chromeno [2, 3-c] pyrazole-4,
30-indoline]-20, 5(6H)-diones (5a)
mp 220 °C (dec); IR (KBr): (vmax/cm-1): 3374 (stretch NH), 3182 (stretch NH),
1691 (stretch CO), 1612 (stretch CO). H NMR (CDCl3, 400 MHz): 0.97 (6H, s,
1
2CH3), 1.40 (3H, s, CH3), 1.90–2.00 (2H, m, CH2), 2.20–2.30 (2H, m, CH2),
6.85–6.86 (1H, m, CH), 6.87–6.88 (1H, m, CH), 6.93–6.94 (1H, m, CH), 7.13–7.14
(1H, m, CH), 11.08 (1H, s, NH), 11.72 (1H, bs, NH) ppm. 13C NMR (CDCl3,
100 MHz): d 11.10, 25.42, 30.50, 42.48, 48.10, 51.82, 97.80, 110.50, 120.28,
124.52, 128.00, 130.73, 133.93, 136.72, 142.55, 146.80, 164.93, 173.74, 198.80.
Anal. Calcd. For C20H19N3O3: C, 68.75; H, 5.48; N, 12.03. Found: C, 68.70; H,
5.50; N 12.02.
3, 7, 7-Trimethyl-50-Chloro-7, 8-dihydro-1H-spiro [chromeno [2, 3-c]
pyrazole- 4, 30-indoline]-20, 5(6H)-diones (5b)
mp 215 °C (dec); IR (KBr): (vmax/cm-1): 3207 (stretch NH), 3110 (stretch NH),
1706 (stretch CO), 1618 (stretch CO), 1473 (aromatic C=C), 806, 769 (C–Cl).1H
NMR (DMSO-d6, 400 MHz, d ppm): 1.01 (6H, s, 2CH3), 1.80 (3H, s,
CH3),1.97–2.00 (2H, m, CH2), 2.21–2.24 (2H, m, CH2), 6.76 (1H, d, J = 8.0 Hz,
CH), 7.12 (1H, d, J = 8.0 Hz, CH), 7.20 (1H, s, CH) 10.56 (1H, s, NH), 11.22 (1H,
bs, NH).13C NMR (100 MHz, DMSO-d6, d ppm): 11.14, 27.44, 30.55, 44.90, 48.12,
52.10, 97.84, 111.10, 120.13, 126.00, 128.63, 130.67, 135.90, 137.00, 141.33,
145.90, 164.34, 172.13, 197.00. Anal. Calcd For C20 H18Cl N3O3: C, 62.58; H, 4.73;
N; 10.95. Found: C, 62.60; H, 4.75; N, 10.90.
3, 7, 7-Trimethyl-50-Bromo-7, 8-dihydro-1H-spiro [chromeno [2, 3-c]
pyrazole-4, 30-indoline]-20, 5(6H)-diones (5c)
mp 185 °C (dec); IR (KBr): (vmax/cm-1): 3216 (stretch NH), 3110 (stretch NH),
1724 (stretch CO), 1608 (stretch CO).1H NMR (DMSO-d6, 400 MHz, d ppm): 1.02
123

A comparative study on the catalytic activity…
(6H, s, 2CH3), 1.80 (s, 3H, CH3), 1.97–2.06 (m, 2H, CH2), 2.21–2.31 (m, 2H, CH2),
6.72 (d, J = 7.2 HZ, 1H, CH), 7.25 (d, J = 7.2 HZ, 1H, CH), 7.32 (s, 1H, CH),
10.33 (s, 1H, NH), 11.58 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6, d ppm):
11.13, 25.33, 33.11, 44.80, 52.68, 97.85, 111.51, 120.28, 124.51, 125.99, 130.74,
133.93, 136.70, 142.56, 146.70, 164.74, 174.33, 197.00. Anal. Calcd. for C20 H18 Br
N3O3: C, 56.09; H, 4.24; N, 9.81. Found: C, 56.06; H, 4.26; N, 9.90.
3, 7, 7-Trimethyl-50-Nitro-7, 8-dihydro-1H-spiro [chromeno [2, 3-c]
pyrazole-4, 30-indoline]-20, 5-(6H) diones (5d)
mp 200 °C (dec); IR (KBr): (vmax/cm-1): 3222 (stretch NH), 3104 (stretch NH),
1735 (stretch CO), 1604 (stretch CO), 1517 and 1336 (stretch N O). 1HNMR
(400 MHz, DMSO-d6, d, ppm): 1.05 (6H, s, 2CH3), 1.80 (s, 3H, CH3), 2.06–2.08 (m,
2H, CH2), 2.26–2.28 (m, 2H, CH2), 7.04 (d, J = 8.4 HZ, 1H, CH), 7.67 (s, 1H, CH),
8.13 (d, J = 8.4 HZ, 1H, CH), 10.18 (s, 1H, NH), 11.36 (s, 1H, NH); 13C NMR
(100 MHz, DMSO-d6): d 11.11, 28.51, 32.16, 42.44, 46.83, 52.16, 97.88, 111.04,
119.41, 126.71, 137.25, 138.51, 144.16, 148.90, 164.02, 173.16, 198.90. Anal. Calcd.
for C20H18 N4O5: C, 60.91; H, 4.60; N, 14.21. Found: C, 60.89; H, 4.55; N, 14.30.
3, 7, 7-Trimethyl-50-Methyl-7, 8-dihydro-1H-spiro [chromeno [2, 3-c]
pyrazole-4, 30-indoline]-20, 5(6H)-diones (5e)
mp 243 °C (dec); IR (KBr): (vmax/cm-1): 3303 (stretch NH), 3191 (stretch NH), 1690
(stretch CO), 1625 (stretch CO).1H NMR (DMSO-d6, 400 MHz, d ppm): 0.94 (6H, s,
2CH3), 1.72 (s, 3H, CH3), 1.83 (s, 3H, CH3), 1.98–2.13 (m, 2H, CH2), 2.17–2.28 (m,
2H, CH2), 6.90 (d, J = 6.9 HZ, 1H, CH), 7.13 (d, J = 6.9 HZ, 1H, CH), 7.48 (s, 1H,
CH), 10.24 (s, 1H, NH), 10.78 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6, d ppm):
10.18, 27.42, 31.76, 32.91, 41.75, 55.68, 98.32, 108.33, 111.54, 121.49, 127.63,
129.48, 135.65, 139.47, 143.12, 145.96, 166.15, 173.35, 197.95. Anal. Calcd. For
C21H21N3O3: C, 69.42; H, 5.78; N, 11.57. Found: C, 69.41; H, 5.80; N 11.53.
Results and discussion
Size distribution and surface morphology of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2–NH2,
and Fe3O4@SiO2–SO3H nanoparticles were investigated by SEM. As is shown in
Fig. 2, SEM images of the samples indicate that the prepared nanoparticles have
spherical shape and uniform size. It is observed that average size of Fe3O4@
SiO2–SO3H and Fe3O4@SiO2–NH2is about 19–33 and 25–31 nm, respectively.
XRD patterns of Fe3O4, Fe3O4@SiO2–SO3H, and Fe3O4@SiO2–NH2 are shown
in Fig. 3. The characteristic peaks in the both spectra are in agreement with the
standard XRD pattern of iron oxide (cubic phase). A broad peak in 2h range of
19°–27° is related to the silica shell coated on Fe3O4 NPs. The crystallite size
diameter (D) of both nanoparticles was calculated by Debye–Scherer equation:
123

F. Alemi-Tameh et al.
Fig. 2 SEM image of a Fe3O4 NPs, b Fe3O4@SiO2 NPs, c Fe3O4@SiO2–NH2 NPs, and d Fe3O4@SiO2–
SO3H
Fig. 3 The XRD pattern of Fe3O4@SiO2–SO3H, and XRD pattern of Fe3O4 and Fe3O4 @SiO2–NH2
123

A comparative study on the catalytic activity…
D ¼ Kk=b cos h
˚
where k is the X-ray wavelength (1.54 A for Cu Ka), h is the Bragg angle of the
maximum of diffraction peak, K is called the shape factor, which usually takes a
constant value of about 0.9, and b is full-width at half-maximum (FWHM). The
crystallite size of Fe3O4@SiO2–SO3H NPs calculated by Debye–Scherer equation is
about 23 nm that well agrees with the result shown by SEM. Also the crystallite size
of Fe3O4@SiO2–NH2 NPs is obtained about 31 nm that well agrees with the result
was shown by SEM.
Room temperature specific magnetization (M) versus applied magnetic field
(H) curve measurements for Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2–SO3H, and
Fe3O4@SiO2–NH2 are illustrated in Fig. 4.
The results demonstrate that all four samples are super paramagnetic and the
highest saturation magnetization is 59.1 emu/g, which belongs to bare MNPs. As
illustrated in Fig. 5, the amount of saturation magnetization for Fe3O4@SiO2NPs,
Fe3O4@SiO2–SO3H, and Fe3O4@SiO2–NH2 is 39.7, 10.43, and 31.7 emu/g,
respectively. The lower saturation magnetization of Fe3O4@SiO2–SO3H and
Fe3O4@SiO2–NH2 than that of Fe3O4@SiO2NPs is attributed to the extra layer
coated onto MNPs. However, it is still high enough to be separated by a magnet.
These results prove that both catalysts can be easily separated and recovered by an
external magnetic field.
The FT-IR spectra of sulfuric acid-functionalized Fe3O4@SiO2, amino-function-
alized Fe3O4@SiO2, Fe3O4@SiO2 , and Fe3O4 NPs are shown in Fig. 5. The peak
appeared at 580–600 cm-1 in all the three spectra is related to characteristic absorption
of Fe–O vibrations. The intense peaks appeared at around 1040–1080 cm-1 are
attributed to asymmetric and symmetric stretching vibrations of Si–O–Si bonds. These
basic characteristic peaks verified that SiO2 was coated on the surface of Fe3O4 NPs.
Fig. 4 The VSM curve of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2–NH2, and Fe3O4@SiO2–SO3H
123

F. Alemi-Tameh et al.
Fig. 5 FT-IR spectrum of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2–NH2, and Fe3O4@SiO2–SO3H NPs
The FT-IR spectrum of amino-functionalized Fe3O4@SiO2 shows the characteristic
peaks at 1442 and 1618 cm-1, which are related to the NH2 bending and C–N
stretching vibrations, respectively. Moreover, the peaks appeared at 2909 and
3413 cm-1 are attributed to stretching vibrations of C–H and N–H bonds, respectively,
indicating Fe3O4@SiO2–NH2 NPs were successfully prepared. In the spectrum of
Fe3O4@SiO2–SO3H, the presence of acid group is confirmed by the strong and broad
peak at 3199 cm-1 , which can be attributed to OH stretching vibration. The presence
of sulfonyl group is also verified by the peaks appeared at 1215 and 1120 cm-1. The
peak at 1120 cm-1 was covered with a stronger absorption peak of Si–O bond at
1076 cm-1. These results reveal that the SO3H groups were successfully adjoined
the surface of Fe3O4@SiO2 nanoparticles. Figure 6 shows the EDS spectra of
Fe3O4@SiO2–SO3H and Fe3O4@SiO2–NH2 NPs.
The presence of elements such as oxygen, iron, silicon, and sulfur was confirmed
in the EDS spectrum of Fe3O4@SiO2–SO3H NPs and their weight percentages were
about 58.14, 22.77, 2.23, and 16.86, respectively. The elemental analysis of
Fe3O4@SiO2–NH2 NPs indicated that the amounts of oxygen, carbon, iron, silicon,
and nitrogen were about 46.83, 10.87, 26.26, 12.00, and 4.04 wt%, respectively.
The results proved that amine and sulfonate groups were successfully coated onto
the surface of MNPs.
Thermal behavior of the prepared catalysts was studied by TGA and the related
curves are shown in Fig. 7. In the both curves, the small weight loss at temperatures
between 30 and 250 °C is attributed to the removal of surface hydroxyl groups and
physically adsorbed solvent molecules trapped in SiO2 layer. The weight loss
observed at 250–450 °C in TGA curve of Fe3O4@SiO2–SO3H NPs is mainly related
123

A comparative study on the catalytic activity…
Fig. 6 a EDS spectrum of Fe3O4@SiO2–SO3H NPs, b EDS spectrum of Fe3O4@SiO2–NH2 NPs
Fig. 7 TGA curve of Fe3O4@SiO2–SO3H and Fe3O4@SiO2–NH2
to the decomposition of SO3H groups grafted to the silica surface. Also, the weight
loss at 250–450 °C in TGA curve of Fe3O4@SiO2–NH2 is due to the decomposition
of APTES group attached to the silica surface. These results confirm that both
catalysts are stable up to 200 °C and can be used in organic reactions.
After preparation and characterization of Fe3O4@SiO2–SO3H and Fe3O4@SiO2–
NH2 nanoparticles, their catalytic activities were investigated in a multicomponent
reaction between dimedone, hydrazine hydrate, ethyl acetoacetate, and isatin as a
model reaction. Initially, we selected various base catalysts such as L-proline, SSLP ,
and Fe3O4@SiO2–NH2 NPs and various acid catalysts such as p-TSA, Silica-SO3H,
sulfamic acid, and Fe3O4@SiO2–SO3H NPs for the model reaction to compare their
catalytic activity. The results were summarized in Table 1 and indicated that
Fe3O4@SiO2–SO3H NPs are the best catalysts considering yields of the product and
reaction time. Moreover, the model reaction was performed in the presence of
different amounts of catalyst. Also, the results clearly reveal that an increase in
catalyst loading from 0.01 to 0.02 g improved the yield of the desired product to a
great extent. The best results were obtained as 94 % yield within 0.5 h with the
catalyst loading of 0.02 g (Entry 15).
123

F. Alemi-Tameh et al.
Table 1 Optimization of reaction conditions using different catalysts
Entry
Catalyst
T/°C
Time (h)
Yielda (%)
1
None
80
80
80
80
80
80
60
70
80
80
80
80
80
80
80
80
70
60
5
Trace
80
90
79
92
92
74
85
92
70
83
81
78
85
94
94
86
76
2
L-proline (20 mol %)
1
3
SSLP (4.8 mol %)
1
4
Fe3O4@SiO2–NH2 (0.01 g)
Fe3O4@SiO2–NH2 (0.02 g)
Fe3O4@SiO2–NH2 (0.03 g)
Fe3O4@SiO2–NH2 (0.03 g)
Fe3O4@SiO2–NH2 (0.03 g)
Fe3O4@SiO2–NH2 (0.035 g)
p-TSA (0.05 g)
1
5
1
6
1
7
1
8
1
9
1
10
11
12
13
14
15
16
17
18
a
5
Silica-SO3H (0.02 g)
2
Sulfamic acid (50 mol %)
Fe3O4@SiO2–SO3H (0.01 g)
Fe3O4@SiO2–SO3H (0.015 g)
Fe3O4@SiO2–SO3H (0.02 g)
Fe3O4@SiO2–SO3H (0.025 g)
Fe3O4@SiO2–SO3H (0.02 g)
Fe3O4@SiO2–SO3H (0.02 g)
0.5
0.5
0.5
0.5
0.5
0.5
0.5
Isolated yield
Table 2 Fe3O4@SiO2–SO3H nanoparticles catalyzed synthesis of spiro [chromeno [2, 3-c] pyrazole-4,
30-indoline]-diones in various solvents in model reaction
Entry
Solvent
Time (min)
Yielda (%)
1
2
3
4
5
a
H2O
30
30
30
30
30
75
EtOH
94
EtOH/H2O (1:1)
CH3CN
CH2Cl2
86
63
Trace
Isolated yield
In another effort, the model reaction was carried out in different solvents such as
H2O, EtOH, CH3CN, CH2Cl2, EtOH/H2O (1:1), and the results are listed in Table 2.
The reaction in CH2Cl2 has afforded the product in poor yields. It is observed that
the reaction progress was appropriate in ‘‘EtOH,’’ and it was selected as the best
solvent (Entry 2).
Using optimized conditions of solvent and catalyst obtained in previous sections,
different spiro [chromeno [2, 3-c] pyrazole-4, 30-indoline]-diones were synthesized
through one-pot four-component reaction of various isatins, 1, 3-cyclohexadiones,
ethyl acetoacetate, and hydrazine hydrate (Table 3). The results show that using
isatin without substituent leads to higher yield than isatin having electron
123

A comparative study on the catalytic activity…
Table 3 One-pot synthesis of spiro [chromeno [2, 3-c] pyrazole-4, 30-indoline]-diones catalyzed by
Fe3O4@SiO2–SO3Ha NPs
Entry
Product
R1
R
X
Time (min)
Yieldb (%)
mp (°C) (dec)
mp (°C) [ref]
(dec)
1
2
3
4
5
6
7
8
9
10
a
5a
5b
5c
5d
5e
5f
H
Me
Me
Me
Me
Me
H
H
30
30
30
30
30
30
30
30
30
30
94
92
89
87
73
85
80
87
85
91
220
215
185
200
195
308
305
241
307
240
–
H
Cl
–
H
Br
–
H
NO2
Me
H
–
H
–
Ph
Ph
Ph
Ph
Ph
312 [27]
310 [27]
244 [27]
315 [27]
243 [27]
5 g
5 h
5i
H
NO2
Br
Me
Me
Me
NO2
H
5j
Reaction conditions: isatin derivatives (1 mmol), ethyl acetoacetate (1.1 mmol), dimedone (1 mmol),
hydrazine hydrate (1.1 mmol), and Fe3O4@SiO2–SO3H NPs (0.02) g
b
Isolated yields
HN
N
O
HN
O
N
O
O
O
H2N
NH2
+
O
O
OEt
O
I
HN
H
N
N
H
N
H2N
HN
N
O
+
O
N
N
N
H
H
H
HN
N
O
O
O
O
O
O
N
H
(II)
H
N
OH
N
O
O
N
N
O
O
- H2O
(II)
+
O
O
O
O
N
N
H
H
=
Fe3O4@SiO2-NH2=
H2N
Scheme 3 Proposed reaction pathway for the synthesis of spiro [chromeno [2, 3-c] pyrazole-4,
30-indoline]-diones using Fe3O4@SiO2–NH2 NPs as catalyst
123

F. Alemi-Tameh et al.
HN
O
N
HN
N
O
O
H2N
NH2
+
HO
O
OEt
I
HN
N
O
O
HO3S
O
HO3S
- H2O
HN
N
O
+
O
N
HO
N
N
N
H
H
H
II
HN
OH
O
N
O
O
N
O
O
OH
+
O
O
N
O
H
N
H
II
H
N
O
N
- H2O
=
SO3H
Fe3O4@SiO2-SO3H=
O
O
N
H
Scheme 4 Proposed reaction pathway for the synthesis of spiro [chromeno [2, 3-c] pyrazole-4,
30-indoline]-diones using Fe3O4@SiO2–SO3H NPs as catalyst
withdrawing groups (such as halides and nitro groups). Electron-donor substituents
such as a methyl group decreased the yield of reaction. The electron-withdrawing
substituents decreased the affinity of the carbonyl group in isatin to coordinate with
the acidic hydrogen of Fe3O4@SiO2–SO3H NPs. Also, it was shown that the yield
of reaction with phenyl hydrazine was reduced compared to hydrazine hydrate
because the intermediate (I) from phenyl hydrazine has lower affinity to condense
with isatin via Knoevenagel reaction.
Enolization is catalyzed by acids and bases. A compound containing a carbonyl
group with acidic a-hydrogen can be simply interconverted to enol form in the
presence of acid or base catalysts. Two types of proposed mechanisms for this
reaction are demonstrated in Schemes 3 and 4.
Scheme 3 shows a proposed mechanism for this reaction in the presence of
Fe3O4@SiO2–NH2 NPs as a base catalyst. Initially hydrazine hydrate is reacted with
1, 3-dicarbonyl compound to form intermediate (I) via condensation reaction. Also,
the carbonyl moiety in isatin is converted to imine group by the nucleophilic attack
of Fe3O4@SiO2–NH2 to isatin. Secondly, intermediate (I) is condensed with isatin
derivatives to form intermediate (II) via Knoevenagel condensation reaction. In the
next step, dimedone reacts with intermediate (II) through Michael addition in the
presence of Fe3O4@SiO2–NH2 NPs. Lastly, the final product is formed by intra-
molecular cyclization reactions. This proposed mechanism has also been supported
by literature [28–30].
123

A comparative study on the catalytic activity…
Fig. 8 Recyclability of Fe3O4@SiO2–SO3H in the reaction
Scheme 4 shows a plausible mechanism for the synthesis of spiro [chromeno [2,
3-c] pyrazole-4, 30-indoline]-diones in the present of Fe3O4@SiO2–SO3H, as an acid
catalyst. Initially, the reaction is started with condensation reaction of 1, 3-dicarbonyl
compound with hydrazine hydrate to form intermediate (I). The electrophilicity of
carbonyl group is increased by a strong coordinated bond formed between carbonyl
groups of isatin and Fe3O4@SiO2–SO3H NPs. Afterward, intermediate (I) is rapidly
condensed with the carbonyl group of the activated isatin to afford intermediate (II),
which can be regarded as a fast Knoevenagel condensation reaction. Then,
intermediate (II), reacts with dimedone through Michael addition. Finally, the intra-
molecular cyclization reactions followed by tautomerization afforded the correspond-
ing product 5. The proposed mechanism is supported by the literature [27].
Reusability is one of the most significant properties of the prepared catalysts. The
recyclability of MNPs-SO3H was studied for the reaction of isatin, hydrazine
hydrate, ethyl acetoacetate, and dimedone. After completion of the reaction, the
nanocatalyst was easily separated using an external magnet. The recovered
magnetic nanoparticles were washed several times with acetone and then dried at
room temperature. Figure 8 indicates that the catalyst could be reused for the
subsequent reaction without any noticeable loss of catalytic activity.
Conclusion
In summary, Fe3O4@SiO2–NH2 NPs and Fe3O4@SiO2–SO3H NPs were employed
respectively as a solid base and acid catalyst for the synthesis of spirooxindole
containing chromene ring fragments in one-pot four-component reactions.
Fe3O4@SiO2–SO3H NPs have been selected as a better catalyst with respect to
the yield of product and reaction times. This nanocatalyst was prepared simply and
removed from the reaction mixtures by using an external magnetic field. Also, using
this catalyst is more cost-effective compared to recently reported catalysts such as
SSLP. Moreover, the products were obtained in excellent yields and short reaction
times compared to using reported traditional acid catalysts such as p-TSA.
123

F. Alemi-Tameh et al.
Acknowledgments The authors are grateful to department of chemistry, Science and Research branch,
Islamic Azad University, Tehran, Iran for supporting this work.
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