Synthesis of novel spirooxindoles in water by using MnFe2O 4 nanoparticles as an efficient magnetically recoverable and reusable catalyst

Article abstract of DOI:10.1016/j.apcata.2013.07.029

An efficient, clean, atom-economical and simple method for the one-pot synthesis of novel spirooxindole derivatives via a three-component reaction of isatins, dimedone and anilinolactones was reported. This reaction was performed by using MnFe₂O₄ nanoparticles (5 mol%) as an efficient magnetically heterogeneous catalyst in water as green solvent. Prominent among the advantages of this method is the use of magnetically recoverable and reusable catalyst, simple work up procedure, good to high product yields and use of water as a solvent that is considered to be relatively environmentally benign.

Full text of DOI:10.1016/j.apcata.2013.07.029

Accepted Manuscript
Title: Synthesis of novel spirooxindoles in water by using
MnFe2O4 nanoparticles as an efficient magnetically
recoverable and reusable catalyst
Author: Ramin Ghahremanzadeh Zahra Rashid Amir Hassan
Zarnani Hossein Naeimi
PII:
S0926-860X(13)00427-4
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2013.07.029
APCATA 14345
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Applied Catalysis A: General
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Revised date:
Accepted date:
24-4-2013
13-7-2013
14-7-2013
Please cite this article as: R. Ghahremanzadeh, Z. Rashid, A.H. Zarnani, H. Naeimi,
Synthesis of novel spirooxindoles in water by using MnFe2O4 nanoparticles as an
efficient magnetically recoverable and reusable catalyst, Applied Catalysis A, General
(2013), http://dx.doi.org/10.1016/j.apcata.2013.07.029
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Synthesis of novel spirooxindoles in water by using MnFe2O4 nanoparticles as an
efficient magnetically recoverable and reusable catalyst
Ramin Ghahremanzadeha, Zahra Rashidb, Amir Hassan Zarnanic, and Hossein Naeimib*
aNanobiotechnology Research Center, Avicenna Research Institute, ACECR, 1936773493, Tehran, I.R. Iran.
bDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 87317, I.R. Iran.
cReproductive Immunology Research Center, Avicenna Research Institute, ACECR, 1936773493, Tehran, I.R. Iran.
Abstract
An efficient, clean, atom-economical and simple method for the one-pot synthesis of novel spirooxindole
derivatives via a three-component reaction of isatins, dimedone and anilinolactones was reported. This reaction
was performed by using MnFe2O4 nanoparticles (5 mol %) as an efficient magnetically heterogeneous
catalyst in water as green solvent. Prominent among the advantages of this method is the use of magnetically
recoverable and reusable catalyst, simple work up procedure, good to high product yields and use of water as a
solvent that is considered to be relatively environmentally benign.
Keywords: Multicomponent reaction, Water, Magnetic nanoparticles, Spirooxindole, Tetronic acid, Isatin,
Dimedone.
1. Introduction
There has been a huge interest in development of highly efficient transformations to form novel structures from
simple building blocks. Synthetic chemists are also in need of finding new, efficient, and simple synthetic routes
leading to greater structural variation in short times with high yields and simple work-up procedures. Significant
advances have been made on to chemical processes to achieve the hazard-free, waste-free, and energy-efficient
syntheses as an ultimate goal. In this context, multicomponent reactions (MCRs) have played an important role
in this area in which the starting materials in a single reaction vessel give a final product [1-3]. The development
of novel, efficient and green MCRs that focus on a target product is one of the major challenges in organic
synthesis. The use of water as green solvent in organic chemistry was rediscovered in the 1980s in Breslow’s
work, which was highlighted that hydrophobic effects could strongly enhance the rate of some organic
reactions. In this effect, hydrophobic molecules in aqueous solution are surrounded by a cage of water
molecules. The condensation of individual molecules to form local domains consisting of multiple hydrophobes
surrounded by water cages is favored by the minimization of the surface area of contact between the
hydrophobic and hydrophilic domains. Therefore, the acceleration of a reaction through the hydrophobic effect
is expected to correlate with the hydrophobic surface area of the reactants [4]. The performance of organic
1
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reactions in water, without the use of any hazardous and flammable organic solvents are some of the
current focuses today especially in our environmentally conscious society [5, 6]. The extensive work has
revealed that a variety of organic reactions can be realized in water especially in the presence of various
catalysts [7-10].
Recently, the magnetic nanoparticles have been widely used as a useful group of heterogeneous
catalysts for organic synthesis, due to their important advantages such as, the remarkable catalytic activity,
easy synthesis, operation simplicity, eco-friendliness, and recoverability by external magnetic field. They
can be separated from the reaction medium after being magnetized by an external magnet. Magnetic
separation is an intriguing alternative to filtration or centrifugation as it prevents the loss of catalyst and
enhances the reusability, rendering the catalyst cost-effective and it is promising for industrial applications
[11-15]. These advantages encouraged us to utilize manganese ferrite nanoparticles as recoverable and
reusable catalyst for the synthesis of novel spirooxindole structures.
Spirooxindole structures are the central skeleton for numerous alkaloids and pharmacologically
important compounds [16] with wide range of useful pharmacological properties and biological activities
such as; antimicrobial [17], antitumoral [18] and antibiotic agents [19] human NK-1 receptor inhibitors [20]
and microtubule assembly inhibitors [21]. For example, Spirotryprostatin B, a natural alkaloid isolated from
the fermentation broth of Aspergillus fumigatus, has been identified as a novel microtubule assembly
inhibitor, also, pteropodine and isopteropodine have been shown to modulate the function of muscarinic
serotonin receptors (Fig. 1) [22-24]. The unique structural array and highly prominent pharmacological
activities have subsequently stimulated interest in the spirooxindole derivatives synthesis, consequently,
much effort has been made to find efficient, new and simple synthetic methods so as to prepare compounds
containing spirooxindole nucleus [25-28].
Figure 1.
In order to evaluate the potential applications of MCRs in the field of heterocyclic chemistry, and to
continue our research towards the development of novel spirooxindoles, employing environmentally benign
reaction medium [29-34], herein we report a simple and efficient one-pot three-component protocol for the
synthesis of new 4-phenyl-6,7-dihydro-[spiro[furo]quinoline-indoline]-triones.
2. Experimental section
2.1 Reagents and Materials
The used chemicals in this work were obtained from Fluka and Merck and used without purification.
Melting points were measured on an Electrothermal 9200 apparatus. IR spectra were
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recorded as KBr pellets on a Perkin-Elmer 781 spectrophotometer and an Impact 400 Nicolet FT-IR
1
13
spectrophotometer. H NMR and C NMR spectra were recorded in DMSO–d6 solvents on a Bruker
DRX-400 spectrometer with tetramethylsilane as internal reference. The elemental analyses (C, H, N)
were obtained from a Carlo ERBA Model EA 1108 analyzer. Nanostructures were characterized using a
Holland Philips Xpert X-ray powder diffraction (XRD) difractometer (Cu K, radiation, k = 0.154056
nm), at a scanning speed of 2°/min from 10° to 100° /(2θ). Scanning electron microscopy (SEM)
micrographs have been collected by a FEI Quanta 200 SEM operated at a 20 kV accelerating voltage.
The purity determination of the substrates and reaction monitoring were accomplished by TLC on
silica-gel polygram SILG/UV 254 plates (from Merck Company).
2.2 Typical experimental procedure for the preparation of catalyst
Manganese ferrite nanoparticles have been synthesized via a number of different popular methods
including co-precipitation, thermal decomposition and/or reduction, micelle synthesis, hydrothermal
synthesis, and laser pyrolysis techniques that all of them can be directed in the synthesis of high-quality
magnetic nanoparticles [35-37]. In this research, the MnFe2O4 nanoparticles have been prepared by
following the reported standard protocol by co-precipitation of MnCl2 and FeCl3 in water in the presence of
sodium hydroxide. Briefly, MnCl2.4H2O and FeCl3.6H2O were taken in molar ratio of Mn2+: Fe3+= 1:2 to
prepare 0.3 mol.L-1 metal ion solution of 100 ml containing 0.1 mol.L-1 Mn2+ and 0.2 mol.L-1 Fe3+, which
was then dropped slowly into 100 ml NaOH solution of 3 mol.L-1 at the temperature of 95 °C. After aging
for 2 h with continuous stirring, the mixture was filtered, washed and dried at 60 °C for 12 h [38].
2.3. Typical procedure for the preparation of 6,6-dimethyl-4-p-tolyl-6,7-dihydro-1H-spiro[furo[3,4-
b]quinoline-9,3'-indoline]-1,2',8(3H,4H,5H)-trione (4b)
A mixture of isatin (1 mmol, 0.147 g), dimedone (1 mmol, 0.140 g), 4-(p-tolylamino)furan-2(5H)-
one (1 mmol, 0.189 g), catalyst (5 mol %, 0.011g) and water (5 mL) was added in a round-bottomed flask
and stirred at 90 °C. After completion of the reaction (monitored by TLC), the catalyst was easily separated
from the reaction mixture with an external magnet. After separation of catalyst, the reaction mixture was
filtered and the precipitate washed with water and recrystallized by EtOH to afford the pure product as
cream powder (0.388 g, Yield: 88%); mp: >300 οC; IR (KBr) ( max/ cm--1): 3439, 2960, 1740, 1665, 1620; 1H
NMR (DMSO-d6, 400 MHz): : 0.99 (3H, s, CH3), 1.02 (3H, s, CH3), 2.01-2.63 (4H, m. 2 CH2), 2.36 (3H, s,
CH ), 4.95 (2H, m, OCH ), 6.94-7.36 (8H, m, ArH), 10.29 (1H, s, NH); 13C NMR (DMSO-d6, 100 MHz): :
3
2
21.2, 27.4, 29.3, 34.4, 36.2, 49.1, 51.2, 65.8, 92.5, 117.2, 120.8, 121.4, 124.0, 127.4, 127.9, 129.0, 130.4,
3
Page 3 of 25

131.3, 137.1, 138.9, 156.3, 160.6, 171.2, 180.1, 190.5; Anal. Calcd for C27H24N2O4: C, 73.62; H, 5.49; N,
6.36; Found C, 73.68; H, 5.54; N, 6.31.
3. Results and discussion
Due to the unique properties of spirooxindole compounds, the development of environmentally benign
synthetic methods which enable facile access to these useful entities will be an interesting challenge. To the
best of our knowledge there are no reports in literature by using of anilinolactones for preparation of
spirooxindoles, and this is the first report for the synthesis of these compounds by using of anilinolactones.
Hence, in this research, firstly, the anilinolactones were prepared from the condensation reaction of tetronic
acid with various anilines. As shown in Scheme 1, when tetronic acid was reacted with an equimolar
amount of various anilines in 1,4-dioxane solution at room temperature, the corresponding products were
obtained in excellent yields, appropriate reaction times and high purity [39].
Scheme 1.
In continuation of this research, considering the highly prominent pharmacological activities of
spirooxindoles, we evaluated the MCR of isatins 1, dimedone 2 and anilinolactones 3 for the synthesis of
novel spirooxindole derivatives 4. The choice of an appropriate reaction medium is of crucial importance
for successful synthesis. For this purpose, isatin 1a, dimedone 2 and, 4-(p-tolylamino)furan-2(5H)-one 3b
as a simple model substrate was investigated to establish the feasibility of the strategy and to optimize the
reaction conditions (Scheme 2).
Scheme 2.
The model reaction was investigated in the presence of a catalytic amount of p-toluenesulfonic acid
(p-TSA), as an inexpensive and available catalyst in ethanol at room temperature, where no reaction
occurred. Subsequently, the reaction mixture was heated to reflux. After stirring for 15 h, TLC analysis
showed that the reaction proceeded, obtaining the product 4a in 64% yield. Based on the above data and in
order to achieve the best results, the reaction conditions were optimized in various solvents. The results are
summarized in Table 1.
Table 1.
As shown in Table 1, when the reaction was carried out in the presence of p-TSA as catalyst in
4
Page 4 of 25

water, the expected product 4b was obtained in high yield (68%) and better reaction time compared with
other organic solvents. It is noteworthy that in some of the above solvents, with non-polar solvents such as
chloroform and toluene due to the low solubility of starting materials, the reaction yield was low and at the
end of the reaction, the starting materials were recovered along with the product. Therefore, water was
chosen as the best solvent of this reaction (Table 1, entry 5).
It was found that when the reaction was carried out without any catalysts the desired product was
obtained in trace amount (by TLC) only along with the unreacted starting materials even after prolonged
reaction time (24 h). This result prompted us to explore the ideal reaction condition to get the maximum
product yield. In the next step, it was made an effort to focus on the search for a suitable catalyst to
improve the reaction yields and to optimize the reaction conditions. We examined the reaction using
different Brønsted and Lewis acids under refluxing water to find the best catalyst. The employed catalysts
were listed in Table 2.
After the extensive screening, it was found that the optimized yields and time profiles were obtained
with manganese ferrite nanoparticles at 90 °C, which lead to the corresponding 6,6-dimethyl-4-p-tolyl-6,7-
dihydro-1H-spiro[furo[3,4-b]quinoline-9,3'-indoline] 1,2',8(3H,4H,5H)-trione 4b in 88% yield through
condensation reaction between isatin 1a, dimedone 2 and 4-(p-tolylamino)furan-2(5H)-one 3b.
Table 2.
3.1. Characterization of the catalyst
The manganese ferrite nanoparticles were prepared by co-precipitation of MnCl2 and FeCl3 in basic
solution at 95 °C using the method in accordance to the literature [39]. The synthesized MnFe2O4 was
characterized by XRD, SEM, and VSM. The position and relative intensities of all peaks are confirmed
well with standard XRD pattern of MnFe2O4 (JCPDS card No. 75-0035) indicating the characteristics of the
cubic structure. The manganese ferrite calcined at 800 °C presented a particle size of 33 nm, calculated
from the broadening of the peak at 2Ɵ = 35.31 using the Scherrer equation (Fig. 2).
Figure 2.
The SEM image shows that manganese ferrite nanoparticles have a mean diameter of about 33 nm
and a nearly spherical shape (Fig. 3). The magnetization curve for MnFe2O4 nanoparticles is shown in Fig.
4. It is of great importance that a catalyst should possess sufficient magnetic and superparamagnetic
properties for its practical application. Magnetic hysteresis measurements on MnFe2O4 were conducted in
an applied magnetic field at room temperature, with the field sweeping from -10000 to +10000 Oersted.
5
Page 5 of 25

As shown in Fig. 4, the hysteresis loop for the sample was completely reversible confirming its super
paramagnetic nature. The catalyst showed high permeability in magnetization and high reversibility in the
hysteresis loop.
Figure 3.
Figure 4.
The amount of catalyst required for this transformation was also evaluated. The model reaction was
performed in the presence of different mol amounts of catalyst. It was found that using 5 mol% manganese
ferrite nanoparticles as a catalyst in water is sufficient to push the reaction forward. Increasing the amount
of MnFe2O4 nano particles to more than 5 mol % did not show any substantial improvement in the yield,
whereas the yield was decreased by decreasing the amount of the catalyst to 5 mol%. Thus, 5 mol% of
catalyst was chosen as maximum quantity of the catalyst for the reaction (Table 3).
Table 3.
Finally, The possibility of recycling the magnetic catalyst was examined by using the reaction of
isatin 1a, dimedone 2, and 4-(p-tolylamino)furan-2(5H)-one 3b as model substrates under optimized
conditions. After completion of the reaction, the catalyst was separated from the reaction mixture by an
external magnet and was washed with acetone, then dried and the recycled catalyst was saved for the next
reaction runs. The procedure was repeated and the results indicated that, the recycled catalyst could be
reused four other times. The isolated yields remain similar with no detectable loss (Figure 5). The SEM
analysis of the recovered nano MnFe2O4 revealed that the morphology and size of the nano particles
remains unchanged (Figure 3).
We have not established an exact mechanism for the formation of these spirooxindoles 4a-p.
However, two reasonable possibilities according to the literatures [12a, 40-43] are indicated in Scheme 3.
Addition of dimedone 2 to activated isatin 1 by nano MnFe2O4 as a Lewis acid leads to highly reactive
intermediate 5 via a standard nucleophilic addition. Interception of 5 by anilinolactone 3 and followed
cyclization catalyzed by nano MnFe2O4 produces the corresponding spirooxindole 4 (Pathway A).
Activated isatin 1 by nano MnFe2O4 and anilinolactone 3 would react to produce highly reactive
intermediate 6, followed by a nucleophilic addition with dimedone 2, finally intra molecular ring closure
leading to the formation of 6,6-dimethyl-4-phenyl-6,7-dihydro-1H-spiro[furo[3,4-b]quinoline-9,3'-indoline]
1,2',8(3H,4H,5H)-trione 4 catalyzed by nano MnFe2O4 (Pathway B). All steps are promoted by Lewis acid
6
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sites of MnFe2O4.
Scheme 3.
Subsequently to verify the general procedure of reaction, a variety of isatins, both electron-donating
and electron-withdrawing groups were reacted with dimedone and various anilinolactones possessing either
electron-donating or electron-withdrawing substituents, under these appropriate reaction conditions (5 mL
of water, reflux, 5 mol% MnFe2O4 nanoparticles). In this reaction, a series spirooxindoles were
synthesized. The results are summarized in Table 4.
Table 4.
The influence of electron-withdrawing and electron-donating substituents on the aromatic ring of
anilinolactone and isatin upon the reaction yields was investigated. The results showed that in isatin, both
electron-withdrawing and electron-donating substituents had no significant effect on the reaction yields.
Anilinolactones with electron-donating group on the aromatic ring reacted rapidly, while anilinolactones
bearing electron-withdrawing group such as -NO2 group decreased the reactivity of anilolactones, and
required longer reaction times.
4. Conclusions
In conclusion, we have developed a potentially efficient, relatively safe and eco-friendly procedure
for the one-pot synthesis of novel spirooxindoles via a three-component condensation reaction of isatins,
dimedone and anilinolactones using manganese ferrite nanoparticles as a powerful and green catalyst in
water. Mild reaction conditions, high product yields, convenient work up, recyclability and reusability of
the magnetic catalyst are the important features of this protocol. Most importantly of all, easy magnetic
separation of the catalyst eliminates the requirement of catalyst filtration after completion of the reaction.
Acknowledgements
We are thankful from Iran National Science Foundation (INSF) for supporting this project
numbered 90002975, University of Kashan for supporting this work by grant number 159148/15, and also
gratefully acknowledge financial support from the Avicenna Research Institute.
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Table 1.
Screening of solvents for the synthesis of 4ba.
Entry
Solvent
Time (h)
24
Yield (%)b
50>
50>
64
1
2
THF
Et2O
24
3
EtOH
15
4
CH3CN
H2O
24
55
5
12
68
6
PhCH3
CH3CO2H
CHCl3
DMSO
Acetone
24
50>
58
7
15
8
24
50>
50>
50>
9
24
10
24
aThe reaction was carried out using isatin (1 mmol), dimedone (1 mmol) and 4-(p tolylamino)furan 2(5H)-one (1 mmol) in the
presence of p-TSA (20 mol%) and solvent (5 mL) at reflux condition .
bIsolated yield of the pure compound
10
Page 10 of 25

Table 2.
Influence of different catalysts for the synthesis of 4ba
Entry
Catalyst
Nano CuFe2O4
Nano MnFe2O4
Nano Fe3O4
Time (h)
Yield (%)b
1
2
6
78
88
6
3
8
65
4
Nano MgO
10
10
12
12
12
12
24
24
58
5
Nano ZnO
52
6
60
p-Toluenesulfonic acid (p-TSA)
Alum
7
57
8
K-10 Montmorillonite
Silica sulfuric acid (SSA)
Bulk ZnO
55
9
54
10
11
50>
50>
Bulk MgO
aThe reaction was carried out using isatin (1 mmol), dimedone (1 mmol) and, 4-(p-tolylamino)furan-2(5H)-one (1 mmol) in the
presence of catalyst (10 mol%) and H2O (5 mL) at 90 °C.
bIsolated yield of the pure compound
11
Page 11 of 25

Table 3.
Optimization amounts of the MnFe2O4 nanoparticles as catalyst in model reactiona
Entry
MnFe2O4 (mol%)
Time (h)
Yield (%)b
1
2
3
4
5
1
2
8
8
6
6
6
76
80
88
88
87
5
10
20
aThe reaction was carried out using isatin (1 mmol), dimedone (1 mmol) and, 4-(p-tolylamino)furan-2(5H)-one (1 mmol) in the
presence of catalyst and H2O (5 mL) at 90 °C.
bIsolated yield of the pure compound
12
Page 12 of 25

Table 4.
Synthesis of novel spirooxindole derivatives 4a
Yieldb
(%)
Entry
R
R1
Product
TON
15.8
HN
O
O
O
O
Cl
O
O
O
H3C
1
79
N
H
N
O
CH3
N
H
Cl
4a
HN
O
O
O
O
O
CH3
O
H3C
O
N
2
88
17.6
O
CH3
N
N
H
H
CH3
4b
HN
O
O
O
O
Br
O
O
H3C
O
O
3
84
16.8
N
N
N
CH3
H
H
Br
4c
HN
O
O
O
OCH
O
O
O
H3C
O
4
82
16.4
N
N
O
CH3
H
N
H
OCH3
4d
13
Page 13 of 25

HN
O
O
O
O
O
O
O
H3C
5
6
85
87
17
O
N
N
N
H
CH3
H
4e
HN
O
O
NO2
O
CH3
O
O
O
O2N
O
H3C
O
17.4
N
N
N
CH3
H
H
CH3
4f
HN
O
NO2
O
O
Cl
O
O
O2N
O
H3C
O
O
7
81
16.2
N
N
N
CH3
H
H
Cl
4g
HN
O
NO2
O
O
O
O
O2N
O2N
H3C
OCH3
O
H3C
O
O
8
9
82
78
75
16.4
15.6
15
N
N
CH3
N
H
H
OCH3
4h
4i
HN
NO2
O
O
O
O
O
O
O
O
H3C
N
H
N
N
CH3
H
HN
O
O
CH3
O
O
O
OCH3
O
O
H3C
O
10
N
N
N
CH3
H
H
OCH3
4j
14
Page 14 of 25

HN
O
CH3
O
O
O
O
CH3
O
H3C
H3C
Br
O
H3C
O
11
12
13
14
79
74
77
81
15.8
14.8
15.4
16.2
N
N
N
CH3
H
H
CH3
4k
HN
O
O
CH3
O
O
Br
O
H3C
O
O
O
N
N
CH3
N
H
H
Br
4l
HN
O
O
Br
O
Br
O
O
O
H3C
O
O
N
N
N
CH3
H
H
Br
4m
HN
O
O
Br
O
O
O
Br
CH3
O
H3C
O
O
N
N
CH3
N
H
H
CH3
4n
HN
O
Br
O
O
O
O
Br
Cl
O
H3C
O
O
15
16
74
76
14.8
15.2
N
N
CH3
N
H
H
Cl
4o
4p
HN
Br
O
O
O
O
O
Br
O
O
O
H3C
N
N
N
H
CH3
H
aReaction conditions: 1a-d (1 mmol), 2 (1 mmol), 3a-f (1 mmol), MnFe2O4 (5 mol%), H2O (5 mL), 90 °C, time reaction 6h.
bIsolated yields
15
Page 15 of 25

Me
H
N
Me
H
O
N
O
O
N
O
H
H
H
H
Me
O
O
O
N
O
OMe
Me
N
N
O
OMe
H
H
H
Isopteropodine
Pteropodine
Spirotryprostain B
Figure 1. Representatives of spirooxindole-containing compounds
16
Page 16 of 25

Figure 2. (a) The X-ray diffraction patterns of calcined MnFe2O4 (b) The authentic
X-ray diffraction patterns of MnFe2O4.
17
Page 17 of 25

Figure 3. The SEM image of MnFe2O4 before the reaction (a) and the SEM image of MnFe2O4 after
the reaction (b)
18
Page 18 of 25

60
40
20
0
-20
-40
-60
-10000 -8000 -6000 -4000 -2000
0
2000 4000 6000 8000 10000
Applied Field(Oe)
Figure 4. The vibrating sample magnetometer curve of synthesized MnFe2O4 nanoparticles.
19
Page 19 of 25

Figure 5. Recyclability of MnFe2O4 nanoparticles on the synthesis of 4b.
20
Page 20 of 25

O
O
H2N
R
O
O
1,4-dioxane
r.t.
HN
+
O
R
Scheme 1. The synthetic route of anilinolactons
21
Page 21 of 25

HN
O
O
O
O
O
O
O
O
O
H3C
+
O
+
HN
N
N
CH3
H
H3C
CH3
1a
2
3b
4b
CH3
CH3
Scheme 2. Model reaction for the synthesis of novel spirooxindoles
22
Page 22 of 25

O
O
H
3
H3C
CH3
N
2
O
O
-H2O
OH
H3C
A
O
CH3
5
NH
O
O
O
O
O
H3C
O
4
O HN
N
CH3
-H2O
O
H
1a
NH
B
O
O
O
O
HN
HO
HN
2
3
6
-H2O
: Manganese ferrite nanoparticles
Scheme 3. The possible mechanism for the synthesis of 4
23
Page 23 of 25

Highlight research:
•
•
•
•
•
An efficient, relatively safe and eco-friendly procedure had been reported.
Novel spirooxindoles via a simple, one-pot three-component reaction synthesized.
Nano MnFe2O4 as a powerful, green, recyclable and reusable catalyst had been used.
Water as a green, safe, inexpensive, and available solvent had been used.
In this method, the reaction times are short and the yields are high.
Page 24 of 25

Synthesis of novel spirooxindoles in water by using MnFe2O4 nanoparticles as
an efficient magnetically recoverable and reusable catalyst
Ramin Ghahremanzadeh, Zahra Rashid, Amir Hassan Zarnani, and Hossein Naeimi*
aNanobiotechnology Research Center, Avicenna Research Institute, ACECR, 1936773493, Tehran, Iran.
bDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 87317, I.R.
Iran.
cReproductive Immunology Research Center, Avicenna Research Institute, ACECR, 1936773493,
Tehran, Iran.
Page 25 of 25