Magnetic calcined oyster shell functionalized with taurine immobilized on β-cyclodextrin (Fe3O4/COS@β-CD-SO3H NPs) as green and magnetically reusable nanocatalyst for efficient and rapid synthesis of spirooxindoles

Article abstract of DOI:10.1007/s11164-019-03860-x

Abstract: Magnetic calcined oyster shell functionalized with taurine immobilized on β-cyclodextrin (Fe₃O₄/COS@β-CD-SO₃H NPs) was prepared as a new stable, long-lived, highly efficient, and exceptional reusable magnetic nan

Full text of DOI:10.1007/s11164-019-03860-x

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03860-x
Magnetic calcined oyster shell functionalized with taurine
immobilized on β‑cyclodextrin (Fe3O4/COS@β‑CD‑SO3H
NPs) as green and magnetically reusable nanocatalyst
for efcient and rapid synthesis of spirooxindoles
Narges Mohammadian1 · Batool Akhlaghinia1
Received: 17 February 2019 / Accepted: 15 May 2019
© Springer Nature B.V. 2019
Abstract
Magnetic calcined oyster shell functionalized with taurine immobilized on
β-cyclodextrin (Fe3O4/COS@β-CD-SO3H NPs) was prepared as a new stable, long-
lived, highly efcient, and exceptional reusable magnetic nanostructured catalyst.
The as-prepared solid acidic catalyst was characterized by various spectroscopic and
microscopic techniques such as Fourier-transform infrared (FT-IR) spectroscopy,
X-ray difraction (XRD) analysis, scanning electron microscopy (SEM), energy-
dispersive X-ray (EDX) spectroscopy, transmission electron microscopy (TEM),
vibrating-sample magnetometry (VSM), thermogravimetric analysis (TGA)/difer-
ential thermogravimetry (DTG), and elemental (CHNS) analysis. The results clearly
showed that the synthesized superparamagnetic catalyst existed as uniform spheres
with average particle size of 16–25 nm. The new magnetic nanocatalyst (Fe3O4/
COS@β-CD-SO3H NPs) was found to be very efective in one-pot multi-compo-
nent reaction of isatin, active methylene component, and 1,3-dicarbonyl compounds
for rapid preparation of spirooxindoles with fused chromenes in water in excellent
yield. The most promising features of the presented approach are the short reaction
time (15–22 min), magnetic separation of the nanostructured catalyst, simple work-
up procedure, reusability of the catalyst for at least eight successive runs without any
appreciable loss of activity, and high product yields (about 94–98%). Surprisingly,
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03860-x) contains supplementary material, which is available to authorized users.
*
Batool Akhlaghinia
akhlaghinia@um.ac.ir
1
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad,
Mashhad 9177948974, Iran
Vol.:(0123456789)
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N. Mohammadian, B. Akhlaghinia
the present methodology proved to be environmentally sustainable, low cost, and
industrially proftable for scale-up and commercialization.
Graphical abstract A novel and green approach for synthesis of spirooxindoles
using a green, inexpensive, and efcient nanocatalyst was investigated.
Keywords Spirooxindoles · Nanocatalyst · Taurine · Fe3O4 /COS@β-CD-SO3H NPs
Introduction
Among N-heterocycle skeletons, the indole nucleus as a ‘‘privileged scafold’’ is
probably the most ubiquitous heterocyclic moiety, being found in a large variety
of natural products and pharmaceuticals [1, 2]. Nitrile-substituted 4H-chromenes
in particular have immense importance as efective drugs in human neurodegen-
erative disorders [3]. Several efective attempts to construct fused spirooxindoles
via one-pot multicomponent reaction of isatin, active methylene component, and
1,3-dicarbonyl compounds are described in literature [4]. This type of reaction has
been achieved using a number of diferent catalysts and conditions, such as trieth-
ylbenzylammonium chloride (TEBA) [5], Et3N [6], I2 [7], tetrabutylammonium
fuoride (TBAF) [8], NH4Cl [9], lipase [10], oxalic acid dihydrate:proline (LTTM)
[11], ZnS nanoparticles [12], sodium stearate [13], butylmethylimidazolium tetra-
fuoroborate ([BMIm]BF4) [14], SiO2-OSO3H NPs [15], amino-functionalized SBA-
15 [16], Cu(OAc)2·H2O [17], ZrO2 nanoparticles [18], nanocrystalline MgO [19],
gluconic acid [20], Mn(bpyo)2/MCM-41 [21], MnFe2O4 nanoparticles [22], silica
sulfuric acid magnetic nanoparticle (SSA-MNPsd) [23], S-alkyl O-hydrogen sul-
fothioate-functionalized silica-coated magnetic nanoparticles (AHST-MNPs) [24],
silica-bonded 5-n-propyl-octahydro-pyrimido[1,2-a]azepinium chloride (SB-DBU)
Cl [25], carbon-SO3H [26], ethylenediammonium diformate (EDDF) [27], and sul-
fated choline-based heteropolyanion [28].
While all reported approaches have their own merits, most of them are associated
with one or more drawbacks such as use of carcinogenic organic solvents, appli-
cation of high temperatures, harsh reaction conditions, poor yield, use of expen-
sive and toxic catalysts, lack of catalyst reusability, consumption of large amounts
of catalyst, and prolonged reaction time. Therefore, owing to the pharmaceutical
1 3

Magnetic calcined oyster shell functionalized with taurine…
importance of spirooxindoles, development of new catalytic systems to overcome
these shortcomings and enable simple, mild, green, and economical synthesis of
spirooxindole derivatives remains important.
Based on the above discussion and our continuing eforts to develop novel and
environmentally benign synthetic methodologies [29–59], we were prompted to
design magnetic calcined oyster shell functionalized with taurine immobilized on
β-cyclodextrin (Fe3O4/COS@β-CD-SO3H NPs) to catalyze one-pot three-compo-
nent synthesis of spirooxindoles with fused chromenes in water with excellent yield
(Scheme 1).
Nowadays, magnetic nanoparticles (MNPs) have acquired immense impor-
tance in organic synthesis due to their unique properties such as high surface
area, low toxicity, superparamagnetic behavior, high degree of chemical stability
in various solvents, easy synthesis and modifcation, cost-efectiveness, and bio-
compatibility [60–63]. In particular, appropriate removal and recycling of Fe3O4
nanoparticles using an external magnet provides a separation method which is
not time-consuming in comparison with standard methods (fltration and cen-
trifugation), prevents loss of the heterogeneous catalyst during the separation
process, and subsequently increases the purity of the products, as well as opti-
mizing operational costs [64]. To improve the chemical stability and also pre-
vent direct contact between magnetic nanoparticles, their surface has been coated
by various materials such as titania [32], chitin [43], carbon [65, 66], polymer
[67, 68], and hydroxyapatite [40]. The resultant nanocomposites with abundant
hydroxyl groups (Fe3O4) on their surface can be efciently functionalized using
various function molecules for many special applications. Use of such function-
alized magnetic nanocomposites or organocatalysts immobilized on coated iron
oxide nanoparticles has been described for a number of organic transformations
in literature [69–72]. Due to our interest in the development of new, efcient,
and environmentally friendly catalysts [29–59], in the present study, synthesis
and characterization of magnetic calcined oyster shell functionalized with tau-
rine immobilized on β-cyclodextrin (Fe3O4/COS@β-CD-SO3H NPs) were car-
ried out and reported for the frst time. Initially, calcined oyster shell nanopar-
ticles (COS NPs) were generated by calcination of waste oyster shells at high
temperature (900 °C for 6 h). Then, COS NPs (I) were magnetized by reaction
between Fe2+ and Fe3+ ions and NH4OH in presence of COS NPs (I). Afterwards,
Scheme 1 Synthesis of diferent structurally spirooxindoles in presence of Fe3O4/CaO@β-CD-SO3H
NPs (V)
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N. Mohammadian, B. Akhlaghinia
in continuation of our previous research on use of solid acids in organic synthe-
sis [34, 38, 42, 46–52], preparation of Fe3O4/COS@β-CD-SO3H NPs (V) as a
new catalyst was investigated through functionalization of Fe3O4/COS NPs (II)
by tosylated β-cyclodextrin (III) then immobilization of taurine (2-aminoethane-
sulfonic acid) on the surface of Fe3O4/COS@β-CDOTs (IV) (Scheme 2).
Scheme 2 Preparation of magnetic calcined oyster shell functionalized with taurine immobilized on
β-cyclodextrin (Fe3O4/COS@β-CD-SO3H NPs, V)
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Magnetic calcined oyster shell functionalized with taurine…
Results and discussion
Characterization of catalyst
Fe3O4/COS@β-CD-SO3H NPs (V) as a magnetically reusable nanocatalyst was syn-
thesized via the stepwise procedure illustrated in Scheme 2. Full characterization
of this newly synthesized nanocatalyst was performed by Fourier-transform infra-
red (FT-IR) spectroscopy, X-ray powder difraction (XRD) analysis, scanning elec-
tron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, transmission
electron microscopy (TEM), vibrating-sample magnetometry (VSM), thermogravi-
metric analysis/diferential thermogravimetry (TGA/DTG), and elemental (CHNS)
analysis.
To confrm successful functionalization of Fe3O4/COS NPs (II) with β-CDOTs
and then taurine, COS NPs (I), Fe3O4/COS NPs (II), β-CDOTs (III), Fe3O4/
COS@β-CDOTs NPs (IV), and Fe3O4/COS@β-CD-SO3H NPs (V) were charac-
terized by FT-IR spectroscopy (Fig. 1). Figure 1a displays the FT-IR spectrum
of COS NPs (I). The absorption band at around 1620–1332 cm−1 corresponds to
stretching vibration of Ca–O bond, corroborating the presence of CaO phase in
the structure of COS NPs. As seen in Fig. 1b, the signifcant new band at around
580 cm−1 is assigned to stretching vibration of Fe–O bond, illustrating success-
ful bonding of Fe3O4 NPs to COS NPs (I) [73]. Broad stretching vibrations of
OH groups were detected at around 3600–3000 cm−1, related to absorptions
by β-CD, –SO3H, and Fe3O4. Also, the absorption band ranging from 2950 to
2780 cm−1 can be attributed to symmetric stretching of CH (Fig. 1c–f) [74, 75].
Fig. 1 FT-IR spectra of (a) COS NPs (I), (b) Fe3O4/COS NPs (II), (c) β-CDOTs (III), (d) Fe3O4/
COS@β-CDOTs (IV), (e) Fe3O4/COS@β-CD-SO3H NPs (V), and (f) Fe3O4/COS@β-CD-SO3H NPs (V)
after eight reuses
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N. Mohammadian, B. Akhlaghinia
The characteristic band of β-CD is evident in the region of 1220–870 cm−1, being
due to asymmetric glycosidic C–O–C vibration. These results confrm success-
ful grafting of β-CDOTs (III) onto the surface of Fe3O4/COS NPs (II) (Fig. 1d).
Absorption bands at 1220–1190 and 1070–1020 cm−1 are related to both asym-
metric and symmetric stretching vibration modes of O=S=O group. N–H bending
and stretching vibrations appeared at 1660–1530 and 3450–3280 cm−1, respec-
tively (Fig. 1e). These results clearly confrm successful immobilization of tau-
rine molecules on the surface of Fe3O4/COS@β-CDOTs (IV) (Fig. 1e).
Also, XRD analysis was applied to evaluate the crystallinity of the COS NPs
and Fe3O4/COS NPs. Figure 2 shows the characteristic peaks at 2θ of 30.5°,
38.1°, 52.6°, 63.2°, 66.9°, and 79.1° corresponding to (1 1 1), (2 0 0), (2 2 0), (3
1 1), (2 2 2), and (4 0 0) crystallographic planes, in agreement with the standard
data for CaO in Joint Committee on Powder Difraction Standards (JCPDS) card
no. 04-007-9734 [76]. The XRD results also demonstrate the presence of cubic
CaO phase with high crystallinity. Moreover, in comparison with the COS NPs
(I), difraction peaks appeared at 2θ = 29.4°, 35.4°, 41.5°, 55.6°, 57.9°, and 62.1°,
being associated with (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1), and (4 4 0) refec-
tions, in good accordance with the cubic phase of Fe3O4 MNPs (JCPDS 04-009-
8428) [77]. The average crystallite size of the COS NPs (I) and Fe3O4/COS NPs
(II) was calculated using the Debye–Scherrer equation d = Kλ/βcosθ, yielding
values of about 20 and 25 nm, respectively.
The morphology of the as-prepared nanostructured catalyst was studied using
scanning electron microscopy (SEM). SEM images of Fe3O4/COS@β-CD-SO3H
NPs (V) (Fig. 3a, b) showed spherical morphology. Furthermore, energy-disper-
sive X-ray (EDX) spectroscopy confrmed the presence of Fe, Ca, Si, S, C, and O
elements in the nanocatalyst structure, as shown in Fig. 4.
Fig. 2 XRD patterns of (a) COS NPs (I), (b) Fe3O4/COS NPs (II), and (c) Fe3O4/COS@β-CD-SO3H
NPs (V)
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Magnetic calcined oyster shell functionalized with taurine…
Fig. 3 SEM images of a, b Fe3O4/COS@β-CD-SO3H NPs (V), and c, d Fe3O4/COS@β-CD-SO3H NPs
(V) after eight reuses
Fig. 4 EDX analysis of Fe3O4/COS@β-CD-SO3H NPs (V)
The size and morphology of the Fe3O4/COS NPs (II) and Fe3O4/COS@β-CD-
SO3H NPs (V) were further characterized by transmission electron microscopy
(TEM). As shown in Fig. 5, most of the particles displayed uniform spherical mor-
phology with average particle size of about 20–50 nm, in good agreement with
the values deduced from the XRD results. It can be seen that β-CDOTs (III) were
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N. Mohammadian, B. Akhlaghinia
Fig. 5 TEM images of a, b Fe3O4/COS NPs (II), c, d Fe3O4/COS@β-CD-SO3H NPs (V), and e, f Fe3O4/
COS@β-CD-SO3H NPs (V) after eight reuses
successfully immobilized on the surface of Fe3O4/COS NPs (II) through the reac-
tion between Fe3O4/COS NPs (II) and –OH groups of the β-CDOTs (III) molecules
(Fig. 5b, c).
The magnetization curves of the Fe3O4/COS NPs (II) and Fe3O4/COS@β-CD-
SO3H NPs (V), which are critical for this application, were measured at ambient
temperature by vibrating-sample magnetometry (VSM). As illustrated in Fig. 6,
1 3

Magnetic calcined oyster shell functionalized with taurine…
Fig. 6 Magnetization curves of (a) Fe3O4/COS NPs (II) and (b) Fe3O4/COS@β-CD-SO3H NPs (V)
the saturation magnetization values of the Fe3O4/COS core–shell (II) and Fe3O4/
COS@β-CD-SO3H NPs (V) were 35.9 and 20.8 emu g−1, respectively, being lower
than the reference value for pure Fe3O4 MNPs [41]. This can be ascribed to com-
munication at the interfaces between the COS NPs and Fe3O4 NPs in the com-
posite [78]. However, the decline in the saturation magnetization of the Fe3O4/
COS@β-CD-SO3H NPs (V) can be attributed to the presence of the organic com-
ponent (β-CD-SO3H) functionalizing the surface of the Fe3O4/COS core–shell
structures(II). Moreover, it is clearly seen from this fgure that no remanence or
coercivity were observed, indicating that the nanoparticles obtained in this study
were superparamagnetic.
The thermal stability and amount of organic segment grafted onto the surface of
Fe3O4/COS NPs were estimated by TGA/DTG of Fe3O4/COS@β-CD-SO3H NPs
(V). As shown in Fig. 7, the TGA thermogram of the nanocatalyst showed a~2.0%
weight loss at temperature near 100 °C, which is due to loss of residual water from
the sample. Further, the next weight loss of~20% from 150 to 630 °C is related to
decomposition of β-CD-SO3H groups on the surface of Fe3O4/COS NPs (II). This
high temperature for β-CD-SO3H elimination indicates the high thermal stability of
Fe3O4/COS@β-CD-SO3H NPs (V). According to the results obtained from TGA,
the amount of organic component supported on the surface of Fe3O4/COS NPs (II)
was estimated to be~3.22 mmol g−1. This result is also in good agreement with
the elemental analysis results, showing carbon, nitrogen, and sulfur content of
C=35.86%, N=4.48%, and S=10.28%.
Furthermore, backtitration was used to determine the amount of carboxyl
groups (acidic sites) on the Fe3O4/COS@β-CD-SO3H NPs (V). To this purpose,
a certain amount (100 mg) of nanoparticles was frst reacted with NaOH solution
(15 mL, 0.1 N), and the resulting mixture was maintained at room temperature for
24 h. Finally, the suspension was fltered and neutralized using standard HCl solu-
tion (0.1 M). According to the volume of HCl consumed (14.1 mL), the number of
acidic sites was found to be 3.20 mmol g−1.
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N. Mohammadian, B. Akhlaghinia
Fig. 7 TGA/DTG thermogram of Fe3O4/COS@β-CD-SO3H NPs (V)
The results of elemental analysis of β-CDOTs (III) and the Fe3O4/COS@β-CD-
SO3H NPs (V) are presented in Table 1, showing good agreement with the TGA
results and the calculation of the amount of acidic sites on the Fe3O4/COS@β-CD-
SO3H NPs (V).
Catalytic synthesis of spirooxindole derivatives
In our initial study, the merit of Fe3O4/COS@β-CD-SO3H NPs (V) (as a het-
erogeneous acidic nanocatalyst) was investigated in the preparation of 2-amino-
7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahydrospiro[chromene-4,3′-indoline]-
3-carbonitrile via one-pot multicomponent reaction of isatin (1 mmol),
malononitrile (1 mmol), and dimedone (1 mmol) as model reaction under dif-
ferent conditions. The results are presented in Table 2. During our optimiza-
tion studies, it was observed that, when the reaction was carried out without
Table 1 CHNS analysis results for β-CDOTs and Fe3O4/COS@β-CD-SO3H NPs (V)
β-CDOTs (III)
Fe3O4/COS@β-CD-SO3H NPs (V)
C
H
N
S
C
H
N
S
wi (calc.)/mass%
wi (found)/mass%
49.36
49.22
5.10
5.04
–
–
10.14
10.09
35.92
35.86
6.54
6.51
4.51
4.48
10.33
10.28
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Magnetic calcined oyster shell functionalized with taurine…
Table 2 Optimization of various reaction parameters for synthesis of 2-amino-7,7-dimethyl-2′,5-dioxo-
5,6,7,8-tetrahydrospiro[chromene-4,3′-indoline]-3-carbonitrile in presence of Fe3O4/COS@β-CD-SO3H
NPs (V)
Entry Catalyst
Catalyst (g) Solvent Tem-
Time (min) Isolated yield (%)
perature
(°C)
1
2
3
4
5
6
7
8
–
–
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
50
50
50
50
50
50
50
50
18 h
18 h
18 h
18 h
18 h
18 h
45
Trace
10
15
20
20
30
95
98
Fe3O4 NPs
COS NPs
Fe3O4/COS NPs
β-CD
Fe3O4/COS@β-CDOTs NPs
Taurine
0.025
0.025
0.025
0.025
0.025
0.025
0.025
Fe3O4/COS@β-CD-SO3H
20
NPs
9
Fe3O4/COS@β-CD-SO3H
NPs
0.025
0.025
0.020
0.015
0.020
0.020
H2O
H2O
H2O
H2O
40
60
50
50
25
95
98
98
90
90
60
10
11
12
13
14
Fe3O4/COS@β-CD-SO3H
20
NPs
Fe3O4/COS@β-CD-SO3H
NPs
20
Fe3O4/COS@β-CD-SO3H
35
NPs
Fe3O4/COS@β-CD-SO3H
NPs
EtOH 50
50
20
Fe3O4/COS@β-CD-SO3H
–
18 h
NPs
catalyst in water at 50 °C, the reaction was incomplete even after 18 h with a
trace amount of the desired product obtained (Table 2, entry 1). To emphasize
the essential role of Fe3O4/COS@β-CD-SO3H NPs (V) in the preparation of
spirooxindoles, in a set of experiments, the model reaction was conducted in
presence of Fe3O4 NPs, COS NPs (I), Fe3O4/COS NPs (II), β-CD, and Fe3O4/
COS@β-CD NPs (III) (Table 2, entries 2–6). In all cases, rather poor yield of
product was obtained. To our delight, use of taurine and Fe3O4/COS@β-CD-
SO3H NPs (V) increased the yield signifcantly with shorter reaction time
(Table 2, entries 7, 8). This is presumed to occur due to the acidity of taurine and
Fe3O4/COS@β-CD-SO3H NPs (V), which promotes the reaction efectively. The
heterogeneity and magnetic reusability of Fe3O4/COS@β-CD-SO3H NPs (V) as
a green and solid acidic catalyst make it the best choice for catalytic preparation
of spirooxindole derivatives. Decreasing the reaction temperature to 40 °C pro-
longed the reaction time to obtain the same yield (Table 2, entry 9), whereas an
increase in the reaction temperature did not lead to any improvement in the yield
of the product (Table 2, entry 10). Several sets of reactions were performed in
presence of diferent amounts of catalyst (Table 2, entries 11, 12). Gratifyingly,
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N. Mohammadian, B. Akhlaghinia
the desired product was produced in high yield when applying 0.020 g catalyst.
To search for the best solvent system for the model reaction, the feasibility of
the model reaction was examined in EtOH, and also under solvent-free condi-
tions (Table 2, entries 13, 14). Interestingly, the results clearly revealed that the
catalyst showed better activity in H2O (98%, 20 min) or EtOH (90%, 20 min)
compared with solvent-free conditions (60%, 18 h). Water and ethanol produced
almost the same results, but based on environmental awareness, cost-efective-
ness, and easy accessibility, we chose water as the solvent.
Having obtained the optimized condition, we delineated the versatility of the
present methodology towards various substrates for synthesis of a series of desired
spirooxindole products through the reaction of variously substituted isatins, dif-
ferent nitrilo active methylene components (malononitrile or ethyl cyanoacetate),
and 1,3-dicarbonyl compounds. The results of this detailed study are presented in
Table 3. The reactions proceeded rapidly, and the desired spirooxindoles with fused
Table 3 Synthesis of diferent structurally spirooxindoles in presence of Fe3O4/COS@β-CD-SO3H NPs
(V)
O
O
O
O
CN
X
O
NH2
R
O
+
+
N
H
R
X
H2O, 50 °C
O
N
H
1
2
3
4a-u
Entry
R
C–H activated
X
Product
Time (min)
Isolated
yield (%)
1
2
3
4
5
6
7
8
H
5-Me
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Cyclohexane-1,3-dione
Cyclohexane-1,3-dione
Cyclohexane-1,3-dione
Cyclohexane-1,3-dione
Cyclohexane-1,3-dione
Cyclohexane-1,3-dione
Cyclohexane-1,3-dione
Cyclohexane-1,3-dione
CN
CN
CN
CN
CO2Et
CO2Et
CO2Et
CO2Et
CN
CN
CN
CN
CO2Et
CO2Et
CO2Et
CO2Et
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
20
15
20
15
20
22
20
20
20
20
20
16
20
20
20
15
98
95
96
98
95
94
95
94
96
95
96
98
94
96
95
96
5-OMe
5-Cl
H
5-Me
5-OMe
5-Cl
H
5-Me
5-OMe
5-Cl
H
5-Me
5-OMe
5-Cl
9
10
11
12
13
14
15
16
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Magnetic calcined oyster shell functionalized with taurine…
tetrahydrochromene derivatives were obtained from a diverse set of reactants in high
yield. The corresponding spirooxindoles (4a–p) were produced after 15–22 min by
one-pot condensation reaction of various isatins (bearing electron-donating groups
as well as electron-withdrawing substituent) with malononitrile or ethyl cyanoac-
etate, and dimedone or cyclohexane-1,3-dione.
Likewise, after longer reaction times, trace amounts of desired products were pro-
duced when using isatins substituted at 4- and 7-position with malononitrile or ethyl
cyanoacetate, and dimedone or cyclohexane-1,3-dione.
All products were crystalline and fully characterized based on their melting point
and mass spectrometry. Additionally, the structures of selected compounds (4a, b, c,
e, g, m, o) were further recognized by FT-IR and 1H and 13C nuclear magnetic reso-
nance (NMR) spectroscopy. The common spectral features of all these compounds
are the presence of cyano and amino groups in the FT-IR spectra; the stretching
frequency appeared in the range of 2200–2190 cm−1, corroborating the presence of
–CN group, while the stretching frequency in the range of 3377–3140 cm−1 corre-
sponds to –NH2 functional group. In the 1H NMR spectra, a broad singlet resonating
in the range of 10.5–10 ppm established the –NH2 at 11-position. Besides, in 13C
NMR spectra, a characteristic peak at around 110–108 ppm verifed the carbon of
cyano group.
According to the above results, the following possible mechanism can be pro-
posed to account for the formation of spirooxindole derivatives in presence of
Fe3O4/COS@β-CD-SO3H NPs (V) via a typical cascade reaction (Scheme 3):
Owing to their acidic nature, Fe3O4/COS@β-CD-SO3H NPs (V) might serve as a
Brønsted-acid catalyst in several stages and play a crucial role in accelerating the
condensation of isatin with nitrilo active methylene components (malononitrile or
ethyl cyanoacetate) to aford I (see Table 2, entry 1). In the subsequent step, the
electron-defcient adduct I is attacked through acid-promoted Michael addition of
activated 1,3-dicarbonyl compound to give intermediate II. Further intramolecular
cyclization furnishes the desired product III. Previous literature reports also support
this proposed mechanism [79].
From the viewpoint of green chemistry, recyclability is an essential aspect for a
good and efcient catalyst. In this regard and to show an additional advantage of
our developed catalytic system, the reusability of Fe3O4/COS@β-CD-SO3H NPs (V)
was studied in the model reaction under the optimized reaction conditions (Table 2,
entry 11). After reaction completion, the magnetic nanocatalyst was easily sepa-
rated using the simple means of a external magnet, washed with EtOH and then
H2O to remove all organic compounds, then dried at 50 °C for 24 h. Then, the nano-
catalyst was reused for the next batch under the same experimental condition and
recycled again. It is interesting to note that almost equal efciency as when using
the fresh nanocatalyst was obtained when using the recovered catalyst up to eight
times (Fig. 8). These results evidently demonstrate that the initial catalytic activity
of the present magnetic nanocatalyst was substantially retained even after repeated
applications.
After completion of eight cycles, we analyzed the magnetic nanocatalyst
using FT-IR spectroscopy, XRD analysis, SEM, and TEM. The FT-IR spectrum
of the Fe3O4/COS@β-CD-SO3H NPs (V) after eight reuses (Fig. 1f) illustrated
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N. Mohammadian, B. Akhlaghinia
Scheme 3 Proposed mechanism for synthesis of spirooxindoles using Fe3O4/COS@β-CD-SO3H NPs (V)
Fig. 8 Synthesis of 2-amino-7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahydrospiro[chromene-4,3′-indoline]-3-
carbonitrile in presence of reused Fe3O4/COS@β-CD-SO3H NPs (V)
1 3

Magnetic calcined oyster shell functionalized with taurine…
that no substantial changes occurred in the chemical structure of the catalyst. All
the characteristic absorption bands of functional groups and hydrogen-bonding
network of the nanocatalyst after uses were well preserved in terms of shape,
position, and relative intensity. Moreover, the XRD results (Fig. 2c) and SEM
(Fig. 3c, d) and TEM images (Fig. 5e, f) of the nanostructured catalyst after right
reuses clearly indicated that no signifcant changes (no signifcant changes or
shifts in the characteristic XRD peaks; no changes in morphology, shape, or size
in SEM and TEM images) occurred in the chemical structure of the catalyst after
eight runs.
Backtitration of the Fe3O4/COS@β-CD-SO3H NPs (V) after right reuses revealed
that the amount of NHCH2CH2SO3H loaded per 1.000 g of nanocatalyst decreased
to 3.15 mmol. This result clearly indicates that 5% (a negligible amount) of the
active acidic sites had leached out from the surface of the catalyst after eight reac-
tion runs (fresh catalyst contained 3.2 mmol –NHCH2CH2SO3H per 1.000 g).
The catalytic ability of Fe3O4/COS@β-CD-SO3H NPs (V) in one-pot
multicomponent
preparation
of
2-amino-7,7-dimethyl-2′,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,3′-indoline]-3-carbonitrile is compared with catalysts
previously reported in literature in Table 4. Although other catalysts can aford high
yield of the product, some of these methods sufer from one or more disadvantages,
such as long reaction time (entries 1–5, 7–11), high catalyst loading (entries 1–11),
corrosive reagent (entry 3), tedious workup procedures and catalyst nonreusability
(entries 1–6).
Conclusions
Fe3O4/COS@β-CD-SO3H NPs (V) were prepared as a new environmentally friendly
magnetic nanostructured catalyst. The as-prepared green solid-phase acidic nano-
catalyst was well characterized by various techniques such as FT-IR spectroscopy,
XRD analysis, SEM, EDX spectroscopy, TEM, VSM, TGA, and elemental analysis
and evaluated in one-pot three-component synthesis of spirooxindoles with fused
chromenes in green solvent (H2O). The characterization results revealed uniform
spherical morphology with average particle size of about 16–25 nm and confrmed
the superparamagnetic behavior of the Fe3O4/COS@β-CD-SO3H NPs (V). Fe3O4/
COS@β-CD-SO3H NPs (V) is highlighted as a better catalyst in terms of product
yield, mild reaction condition, reaction time, use of H2O as green reaction medium,
and simple experimental and isolation procedures. The magnetic acidic catalyst was
prepared simply, removed from the reaction mixture using an external magnetic
feld, and reused eight times without appreciable loss of activity. Use of this catalyst
is more cost-efective compared with recently reported catalysts. Due to the advan-
tages of this protocol over previously reported methods, it can be expected that the
present methodology will fnd extensive application in combinatorial chemistry as
well as in multicomponent green synthesis to aford diferent types of spirooxin-
dole fused heterocycles. Moreover, as this method does not involve use of hazardous
organic solvents, it can be classifed as a green chemistry approach.
1 3

N. Mohammadian, B. Akhlaghinia
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Magnetic calcined oyster shell functionalized with taurine…
Experimental
General
All chemical reagents and solvents were purchased from Merck and Sigma-Aldrich
chemical companies and used as received without further purifcation. Purity deter-
minations of the products were accomplished by thin-layer chromatography (TLC)
on silica gel Polygram SIL G/UV 254 plates. Melting points of products were deter-
mined using an Electrothermal type 9100 melting point apparatus. FT-IR spectra
were obtained from pressed KBr pellets using an AVATAR 370 FT-IR spectrometer
(Thermo Nicolet, USA) at room temperature in the range from 4000 and 400 cm−1
with resolution of 4 cm−1. Elemental analysis was performed using a Thermo Finni-
gan Flash EA 1112 series instrument. NMR spectra were obtained using Bruker
Avance 300 MHz instruments in dimethylsulfoxide (DMSO)-d6. Mass spectra were
recorded with a CH7A Varian MAT Bremen instrument at 70 eV electron impact
ionization and are reported in m/z (rel %). The crystal structure of the catalyst was
analyzed by XRD using a Bruker D8 Avance difractometer operated at 40 kV and
30 mA with Cu Kα radiation (λ=0.154 Å). SEM images were recorded using a
Leo1450 VP scanning electron microscope at accelerating voltage of 20 kV. Ele-
mental compositions were determined using an SC7620 energy-dispersive X-ray
(EDX) instrument presenting 133 eV resolution at 20 kV. Transmission electron
microscopy (TEM) was performed with a Leo 912 AB microscope (Zeiss, Ger-
many) at accelerating voltage of 120 kV. TGA was carried out using a Shimadzu
thermogravimetric analyzer (TG-50) in the temperature range of 25–900 °C at
heating rate of 10 °C min−1 under air atmosphere. The magnetic properties of the
catalyst were measured using a vibrating-sample magnetometer (VSM, 7400 Lake
Shore). All products are known compounds and were characterized based on their
FT-IR, 1H NMR, and 13C NMR, and mass spectra plus comparison of their melting
points with known compounds. All yields refer to isolated products after purifcation
by recrystallization.
Preparation of calcined oyster shells (I)
Oyster shells were washed several times with H2O/EtOH to remove impurities, then
dried for 12 h at 100 °C. The oyster shells were crushed and milled to obtain fne
powder. Subsequently, calcined oyster shells (COS) were generated by calcination of
waste oyster shells at high temperature (900 °C for 6 h).
Hydrothermal synthesis of Fe3O4/COS NPs (II)
A suspension of calcined oyster shell (COS) (2 g) in deionized water (150 mL) was
added to a 500-mL three-necked fask. Then, FeCl3·6H2O (9.2 mmol, 2.48 g) and
FeCl2·4H2O (4.6 mmol, 1.26 g) were added to the white suspension. The result-
ing mixture was mechanically stirred for 3 min at room temperature under Ar
1 3

N. Mohammadian, B. Akhlaghinia
atmosphere. Subsequently, ammonium hydroxide (20 mL, 25%) was dropped very
slowly into the mixture under stirring. The resulting black mixture was stirred con-
tinuously for 5 h at 75 °C under Ar atmosphere. Finally, the mixture was permitted
to cool to room temperature, and Fe3O4/COS MNPs were separated by an exter-
nal magnet and washed with deionized water several times before being dried under
vacuum at 50 °C overnight.
Preparation of tosylated β‑cyclodextrin (β‑CDOTs) (III)
To a suspension of β-CD (1 mmol, 1.134 g) in water (10 mL), NaOH (7 M, 2 mL)
was added dropwise slowly. When the suspension turned to a homogeneous phase,
the fask was immersed in an ice–water bath. Afterward, a solution of p-toluene-
sulfonyl chloride (10.5 mmol, 2 g) in acetonitrile (4 mL) was dripped into the clear
solution over 20 min. After stirring for 3 h at ambient temperature, the remaining
precipitate was refrigerated overnight at 4 °C. Subsequently, the white precipitate
was removed by fltration and recrystallized from hot water to obtain a pure white
solid (1.971 g, 89%).
Preparation of Fe3O4/COS@β‑CDOTs NPs (IV)
Fe3O4/COS NPs (1 g) were dispersed in dry DMF by sonication for 20 min, then
β-CDOTs (1.32 mmol, 1.5 g) was added to the suspension. The mixture was refuxed
with vigorous stirring. After 24 h, the resulting Fe3O4/COS@β-CDOTs NPs were
collected using an external magnet, washed with distilled water, then dried at 50 °C
for 6 h.
Preparation of magnetic calcined oyster shell functionalized with taurine
immobilized on β‑cyclodextrin (Fe3O4/COS@β‑CD‑SO3H NPs) (V)
Taurine (40.00 mmol, 5 g) was added to a suspension of Fe3O4/COS@β-CDOTs
NPs (V) (1 g) in distilled water (80 mL) with stirring at 60 °C. After 24 h, the mix-
ture was permitted to cool to room temperature. Thereafter, Fe3O4/COS@β-CD-
SO3H nanoparticles (V) were separated by an external magnet and washed with
deionized water several times before being dried under vacuo at 50 °C overnight.
Typical procedure for preparation of 2‑amino‑7,7‑dimethyl‑2′,5‑dioxo‑5,6,7,8
‑tetrahydrospiro[chromene‑4,3′‑indoline]‑3‑carbonitrile in presence of Fe3O4/
COS@β‑CD‑SO3H NPs (V)
Fe3O4/COS@β-CD-SO3H NPs (V) (0.02 g) were added to a mixture of isatin
(1 mmol, 0.147 g), 5,5-dimethylcyclohexane-1,3-dione (dimedone) (1 mmol,
0.140 g), and malononitrile (1 mmol, 0.066 g) in water (4 mL). The mixture was
magnetically stirred at 50 °C, for 20 min. Reaction progress was monitored by TLC
(n-hexane:EtOAc, 3:1). Upon reaction completion, the catalyst was removed by an
external magnet, washed with water (10 mL), and dried overnight to be ready for the
1 3

Magnetic calcined oyster shell functionalized with taurine…
next run. The formed solid was fltered of, washed with warm water, then dried to
obtain pure products (0.328 g, 98%).
Acknowledgements The authors gratefully acknowledge partial support of this study by Ferdowsi Uni-
versity of Mashhad Research Council (Grant no. 3/43388).
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