HPA decorated Halloysite Nanoclay: An efficient catalyst for the green synthesis of Spirooxindole derivatives

Article abstract of DOI:10.1002/aoc.4113

A novel heterogeneous catalyst, HPA@HNTs-IMI-SO₃H, was designed and synthesized based on functionalization of halloysite nanotubes with ionic liquid and subsequent incorporation of heteropolyacid. The structure of the catalyst was studied and confirmed by using SEM/EDX, FTIR, XRD, ICP-AES, TGA, DTGA and BET. Moreover, the catalytic activity of HPA@HNTs-IMI-SO₃H was investigated for promoting ultrasonic-assisted three-component reaction of isatines, malononitrile or cyanoacetic esters and 1,3-dicarbonyl compounds to afford corresponding spirooxindole in high yields and short reaction time. The reusability of the catalyst was also studied. Notably, the catalyst could be recovered and reused for three reaction runs. However, reusing for fourth reaction runs led to the decrease of the catalytic activity. Considering leaching test results, that observation was attributed to the leaching of heteropolyacids, which can be induced by ultrasonic irradiation.

Full text of DOI:10.1002/aoc.4113

Received: 18 July 2017
DOI: 10.1002/aoc.4113
Revised: 28 August 2017
Accepted: 30 August 2017
F U L L P A P E R
HPA decorated Halloysite Nanoclay: An efficient catalyst for
the green synthesis of Spirooxindole derivatives
Samahe Sadjadi1
| Majid M. Heravi2
| Masoumeh Malmir2 | Baharak Masoumi2
1 Gas Conversion Department, Faculty of
Petrochemicals, Iran Polymer and
Petrochemical Institute, PO Box
14975‐112, Tehran, Iran
2 Department of Chemistry, School of
Science, Alzahra University, PO Box
1993891176, Vanak, Tehran, Iran
A novel heterogeneous catalyst, HPA@HNTs‐IMI‐SO3H, was designed and
synthesized based on functionalization of halloysite nanotubes with ionic
liquid and subsequent incorporation of heteropolyacid. The structure of
the catalyst was studied and confirmed by using SEM/EDX, FTIR, XRD,
ICP‐AES, TGA, DTGA and BET. Moreover, the catalytic activity of
HPA@HNTs‐IMI‐SO3H was investigated for promoting ultrasonic‐assisted
three‐component reaction of isatines, malononitrile or cyanoacetic esters
and 1,3‐dicarbonyl compounds to afford corresponding spirooxindole in high
yields and short reaction time. The reusability of the catalyst was also studied.
Notably, the catalyst could be recovered and reused for three reaction
runs. However, reusing for fourth reaction runs led to the decrease of the
catalytic activity. Considering leaching test results, that observation was
attributed to the leaching of heteropolyacids, which can be induced by
ultrasonic irradiation.
Correspondence
Samahe Sadjadi, Gas Conversion
Department, Faculty of Petrochemicals,
Iran Polymer and Petrochemical Institute,
PO Box 14975‐112, Tehran, Iran.
Email: samahesadjadi@yahoo.com;
s.sadjadi@ippi.ac.ir
Majid Heravi, Department of Chemistry,
School of Science, Alzahra University, PO
Box 1993891176, Vanak, Tehran, Iran.
Email: mmh1331@yahoo.com;
mheravi@alzahra.ac.ir
KEYWORDS
halloysite, hybrid, ionic liquid, nanocatalyst, spirooxindole
1 | INTRODUCTION
clusters. The unique feature of HPAs and their salts is that
they can exert both acidic (Bronsted acidity(and redox
Spirooxindole derivatives such as are biologically‐
attractive heterocycles which can be found in alkaloids
and pharmaceuticals. The synthesis of these compounds
is an appealing target in the organic synthesis due to their
diverse biological activities including fungicidal, anti-
convulsant, herbicidal and anti‐cancer properties.[1,2]
Spirooxindoles can also be used as a key intermediate
for the synthesis of clinical pharmaceuticals.[3] To date
many attempts have been devoted to disclose efficient
protocols for the synthesis of spirooxindoles. In this line,
the utilities of many catalysts such as triethylamine,
piperidine, ethylenediamine diacetic acid, L‐Proline,[4]
chiral phoshoic acid[5] and potassium tetrachloroaurate
trihydrate have been proved.[1]
activity.[6] This outstanding property renders these
catalysts bi‐functional and broadens their applications as
efficient catalysts in catalytic processes.[7–10] Considering
the non‐toxic and non‐corrosive entity of HPA, they can
be very promising for developing green protocols for the
synthesis of various chemicals. However, HPAs are highly
soluble in water and most organic solvents which is a
drawback from the green chemistry and industrialization
point of views. To circumvent this issue, immobilization
of HPA on heterogeneous supports such as zeolites and
clays has been suggested.[11,12]
Halloysite nanotubes, HNTs, are naturally oc-
curring clays with the general formula of
(Al2(OH)4Si2O5·2H2O).[13,14] The HNTs tubes are relatively
long (~ 100 nm to 4000 nm).[15] Moreover, the external
diameters of HNTs range from 30 to 190 nm while their
Heteropolyacids, HPAs, belong to a class of inorganic
compounds that are composed of cations and polyanion
Appl Organometal Chem. 2017;e4113.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 12
https://doi.org/10.1002/aoc.4113

2 of 12
SADJADI ET AL.
internal diameters vary between 10–100 nm.[16] This
structure of HNTs as well as their biocompatibility,
abundance, high mechanical and thermal stability and
surface area makes them promising candidates for using
as drug delivery system[17] and loading catalytic active
species.[17,18] Notably, the applications of HNTs are
not limited to the abovementioned fields. They also
proved to be efficient for optical, magnetic and electrical
applications,[17] water treatment,[19] and membrane for
gas separation.[20] Recently, the functionalization of HNTs
surface has gained growing interest.[21] The functionalized
HNTs can be considered as an efficient hybrid system for
accommodating diverse range of active species such as
catalytic species.[22,23]
gel 60 F254, visualized, using ultraviolet light. Melting
points were determined in open capillaries using an
Electrothermal 9100 without further corrections.
HPA@HNTs‐IMI‐SO3H was fully characterized by
using various analytical techniques including BET, FTIR,
SEM/EDX, Thermogravimetric analysis (TGA), DTGA,
XRD, and ICP‐AES. TGA was carried out on a METTLER
TOLEDO thermogravimetric analysis apparatus with a
heating rate of 10 °C min−1 from 50 to 600 °C under N2
atmosphere. FTIR spectra of the fresh and reused catalyst
were recorded by using PERKIN‐ELMER‐ Spectrum 65
instrument. Room temperature powder X‐ray diffraction
patterns were obtained by using a Siemens, D5000. CuKα
radiation from a sealed tube. SEM/EDX images were
obtained by a Tescan instrument, using Au‐coated sam-
ples and acceleration voltage of 20 kV. The BET analyses
of the catalyst and pure HNTs were carried out by
employing BELSORP Mini II instrument. Prior to BET
analyses, the catalyst or pure HNTs were degassed at
423 K for 3 h. The ultrasonic apparatus applied for
performing the organic reactions was Bandelin HD 3200
with output power of 150 W and tip TT13.
In the following of our research[18,24–28] on the synthe-
sis of novel heterogeneous catalysts and disclosing mild
and environmentally benign methodologies for organic
transformations, herein, we wish to present a novel
hybrid catalytic system, HPA@HNTs‐IMI‐SO3H, consists
of heteropolyacids, ionic liquids and halloysite nanoclay
as an efficient and heterogeneous catalyst for promoting
the synthesis of spirooxindole from reaction of isatines,
malononitrile or cyanoacetic esters and 1,3‐dicarbonyl
compounds (Scheme 1). The reaction proceeded rapidly
in the mixture of ethanol and water under ultrasonic
irradiation as a green and environmentally benign protocol
to afford the desired products in excellent yields. The
reusability of the catalyst as well as the HPA leaching is
also studied to disclose the nature of the catalysis and
stability of the catalyst.
2.2 | Synthesis of HNTs/cl
HNTs (1.2 g) was added into a mixture of 4 ml
(3‐chloropropyl)trimethoxysilan in 50 ml dry toluene.
Then, to obtain a homogenized mixture, the suspension
was subjected to ultrasonic irradiation for half an hour.
Subsequently the mixture was refluxed for 24 h at 110 °C.
Upon completion of the reaction, the reaction mixture
was cooled to ambient temperature and the precipitate
was filtered off, washed with dry toluene repeatedly and
dried at 80 °C overnight.
2 | EXPERIMENTAL
2.1 | Material and instrument
All chemicals and reagents used for the synthesis of
the catalyst including halloysite clay, (3‐chloropropyl)
trimethoxysilan, imidazole, 1,2‐oxathiane 2,2‐dioxide,
phosphotungstic acid, EtOH, toluene, water and acetoni-
trile were analytical grade reagents, purchased from
Sigma‐Aldrich, and used as received. The organic com-
pounds employed for the synthesis of spirooxindoles
included isatines, malononitrile, cyanoacetic esters, 1,3‐
dicarbonyl compounds and were provided from Merck.
The progress of the organic processes was monitored by
TLC on commercial aluminium‐backed plates of silica
2.3 | Synthesis of HNTs/1‐(3‐
(trimethoxysilyl)propyl)‐1H–imidazole
(HNTs‐IMI)
In this step, a mixture of imidazole (1.361 g, 22 mmol) and
HNTs/Cl (1.5 g) in 50 ml dry toluene were refluxed at
80 °C for 48 h in the absence of any catalyst. After the
end of the reaction, the obtained product was washed
with diethyl ether (3*10 ml) and dried at 80 °C in oven
for 12 h, to yield a cream powder.
O
O
NH2
O
O
O
Catalyst (0.025 g)
R4
O
O
+
R4
CN
+
N
H
H2O: EtOH, 8:2
r.t., 80 W
R1
N
SCHEME 1 Three‐component reaction
R1
H
catalyzed by HPA@HNTs‐IMI‐SO3H
under ultrasonic irradiation
R1 (1a, b)
R2, R3 (2a, b) R4 (3a, b)

SADJADI ET AL.
3 of 12
2.4 | Synthesis of HNTs/4‐(1‐(3‐
(trimethoxysilyl)propyl)‐1H–imidazol‐3‐
ium‐3‐yl)butane‐1‐sulfonate (HNTs‐IMI‐
SO3H)
2.6 | Synthesis of spirooxindole in the
presence of HPA@HNTs‐IMI‐SO3H as
catalyst
A tube was charged with a mixture of isatines (1 mmol),
malononitrile or cyanoacetic esters (1 mmol), 1,3‐
dicarbonyl compounds (1 mmol), and HPA@HNTs‐IMI‐
SO3H as a catalyst (0.025 g) in H2O/EtOH (8:2, 10 ml).
The reaction mixture was then sonicated at 80 W at room
temperature for proper reaction time (Table 2). After com-
plete conversion (monitored by TLC), 10 ml of hot EtOH
was added into the reaction mixture to dissolve the
resulting products. Then, the catalyst was filtered, washed
with EtOH and dried at 90 °C overnight for reusing in
consecutive reaction runs. The filtrate on the other hand,
was cooled to room temperature to let the dissolved prod-
ucts crystalize. Then, the product was filtrated. Finally,
the pure product was achieved by recrystallization from
hot EtOH.
To a suspension of HNTs‐IMI (1 g) in dried toluene, 1,2‐
oxathiane 2,2‐dioxide (5.8 mmol, 0.75 g) was added. The
as‐made mixture was then stirred overnight. At the end
of the reaction, the cream powder was filtered, washed
with dry toluene and dried at 80 °C in oven for 12 h.
2.5 | Immobilization of HPA on HNTs‐
IMI‐SO3H: Synthesis of HPA@HNTs‐IMI‐
SO3H
Wetness impregnation method was used to immobilize
phosphotungstic acid on HNTs‐IMI‐SO3H. To this pur-
pose, a mixture of HNTs‐IMI‐SO3H (1 g) in acetonitrile
(25 ml) were prepared and stirred vigorously. Then, a
solution of H3PW12O40 (0.2 g) in acetonitrile (5 ml) was
dropwise added to the suspension. The resulting mixture
was subsequently stirred vigorously at ambient tempera-
ture overnight. Upon completion of the reaction, the solid
was filtered, washed with acetonitrile and dried in oven at
90 °C overnight. The schematic synthesis of the catalyst is
described in Figure 1.
3 | RESULT AND DISCUSSION
3.1 | Characterization of HPA@HNTs‐
IMI‐SO3H as catalyst
The FTIR spectra of HPA@HNTs‐IMI‐SO3H and pure
HNTs are depicted in Figure 2. As shown, the FTIR
FIGURE 1 Synthesis of HPA@HNTs‐IMI‐SO3H as catalyst

4 of 12
SADJADI ET AL.
FIGURE 2 FTIR spectra of pure HNTs
(a) and HPA@HNTs‐IMI‐SO3H (b)
spectrum of the catalyst clearly exhibited the characteris-
tic bands of HNTs, i.e. the bands at 669 cm−1 and
1660 cm−1which are indicative of Al‐O‐Si vibration and
the interlayer water as well as the bands at 3702 cm−1
and 3693 cm−1 which can be assigned to internal and
external hydroxyl groups of HNTs structure. The compar-
ison of FTIR spectra of HPA@HNTs‐IMI‐SO3H and pure
HNTs established that the two FTIR spectra are distin-
guished to some extent and the FTIR spectrum of the
catalyst exhibited some additional bands and broadening
of some bands. More precisely, an additional band can
be observed at 2954 cm−1which can be assigned to –CH2
stretching, confirming the conjugation of (3‐chloropropyl)
trimethoxysilan. Moreover, the broad band, broaden in
the range of 1042–1154 cm−1can be assigned to the Si–O
stretching as well as the sulfur trioxide ion. This observa-
tion along with the increase in the intensity of the band at
1660 cm−1, which can also be assigned to the C = N
stretching, can confirm the presence of ionic liquid in
the structure of the catalyst. Finally, The sharp bands at
808 and 783 cm−1 can be assigned to symmetric stretching
of W–Oc–W, W–Oe–W respectively and proved the pres-
ence of heteropolyacid.[29] It is worth noting that due to
the overlap of some characteristic bands, FTIR spectros-
copy cannot individually prove the formation of the
catalyst. Hence, other analyses were performed to establish
the structure of the catalyst.
structure. Moreover, the observation of C, N and S atoms
in EDX is indicative of incorporation of IMI‐SO3H in the
catalyst structure. The immobilization of HPA can be
confirmed by the presence of the W and P atoms in
EDX image.
The structure of HPA@HNTs‐IMI‐SO3H was also
analyzed by XRD analysis. In Figure 4 the XRD patterns
of HPA@HNTs‐IMI‐SO3H and pure HNTs are illustrated.
The comparison of the XRD patterns indicated that both
patterns exhibits peaks at 8°, 13°, 23°, 28°, 31°, 58° and
67° which are representative of HNTs structure (JCPDS
No. 29–1487).[16,30] This observation demonstrated that
the HNTs functionalization with IMI‐SO3H and incorpo-
ration of HPA did not collapse of HNTs framework.
Noteworthy, the unchanged interlayer distances of
HPA@HNTs‐IMI‐SO3H established that the functionality
and HPA did not located within the interlayer of HNTs,
but on the surface and the edges of the HNTs tubes. This
is in good agreement with previous reports.[16]
The thermal stability HPA@HNTs‐IMI‐SO3H was
studied by using of TGA and DTGA analyses. In
Figure 5 the thermogram of HPA@HNTs‐IMI‐SO3H is
illustrated. Compared to pure HNTs which showed one
degradation step due to loss of water[31,32] over the range
of 35–550 °C, the TGA thermogram of HPA@HNTs‐IMI‐
SO3H possessed two degradation stages. The initial degra-
dation stage is due to the loss of adsorbed H2O molecules
in the catalyst. The next one, however, can be assigned to
the thermal decomposition of organic component.
Using TGA analysis the weight percentage of organic
motif in HPA@HNTs‐IMI‐SO3H was calculated to be
about 18 w/w%.
The SEM images of HPA@HNTs‐IMI‐SO3H are
illustrated in Figure 3. As shown, the catalyst exhibited
the rod like morphology which packed together to form
aggregates. This morphology is very similar to that of pure
HNTs, Figure 3, indicating that functionalization and
HPA incorporation did not destruct the morphology of
the HNTs.
The EDX image of HPA@HNTs‐IMI‐SO3H is depicted
in Figure 3. As shown, Si, Al and O atoms are present in
the EDX image which can be representative of the HNTs
To study the textural properties of HPA@HNTs‐
IMI‐SO3H and elucidate whether the incorporation of
HPA and IMI‐SO3H can affect these properties, Nitrogen
adsorption–desorption isotherms of HPA@HNTs‐IMI‐
SO3H and pure HNTs were obtained and compared,

SADJADI ET AL.
5 of 12
FIGURE 3 a) the SEM–EDX picture of HPA@HNTs‐IMI‐SO3H, b) SEM image of HNTs
Figure 6. As shown, both isotherms exhibited the shape
which is in good agreement with the type II nitrogen
adsorption–desorption isotherms with H3 hysteresis
loops.[16] This observation clearly established that both
HPA@HNTs‐IMI‐SO3H and pure HNTs possess porous
structure. Moreover, it can be concluded that upon
functionalization of HNTs and incorporation of HPA, the
porous structure of HNTs was preserved. It was also found
that upon functionalization and HPA incorporation, the
specific surface area of pure HNTs (~ 51 m2 g−1) increased
and reached to ~99 m2 g−1.Moreover, compared to HNTs,
the average pore diameter and total pore volume increased

6 of 12
SADJADI ET AL.
FIGURE 4 XRD pattern of
HPA@HNTs‐IMI‐SO3H
FIGURE 5 TGA and DTGA analysis of
HPA@HNTs‐IMI‐SO3H
in HPA@HNTs‐IMI‐SO3H (Table 1). These observations
are in good agreement with the previous reports in which
the increase in specific surface area was attributed to the
presence of catalytic species on HNTs surface.[33] Accord-
ing to the previous reports,[34] the increase of average pore
diameter and total pore volume could be attributed to the
presence of more interparticle pores of the composites.
To calculate the amount of heteropolyacid
biologically active spirooxindole from three component
reaction of isatines, malononitrile or cyanoacetic esters
and 1,3‐dicarbonyl compounds. In this context, the reac-
tion of malononitrile, isatines and dimedone was selected
as the model reaction. Notably, the ultrasonic irradiation
was used to promote an efficient, green and rapid route
for the synthesis of spirooxindole. Initially, the model
reaction was performed in the absence of the catalyst
(Table 2). It was found that the reaction proceed very
slowly (2 h) in the absence of the catalyst and only a trace
amount of the desired product was obtained. Hence, the
necessity of the use of the catalyst was confirmed. Next,
the reaction variables including, the catalyst amount,
solvent and power of ultrasonic irradiation were
optimized. As development of a green methodology was
targeted, water was first selected as the reaction solvent.
Comparison of the yield of the desired product in water
as solvent with those of some organic solvents such as
toluene or acetonitrile confirmed the superior efficiency
of the water as a solvent. However, the yield of the model
in HPA@HNTs‐IMI‐SO3H,
a
known amount of
HPA@HNTs‐IMI‐SO3H was digested in concentrated
HCl and HNO3 solution. Then, the extract was subjected
to ICP‐AES analysis. Through this procedure, the content
of heteropolyacid was estimated to be about 4 wt%.
3.2 | Catalytic activity
In the next step, we move on to study the catalytic activity
of the HPA@HNTs‐IMI‐SO3H for promoting chemical
transformations. In this line, we selected synthesis of

SADJADI ET AL.
7 of 12
FIGURE 6 The N2 adsorption–
desorption isotherm of HPA@HNTs‐IMI‐
SO3H
product in water was not comparative to some of the
previous reports. To increase the yield of the product,
ethanol was used as a co‐solvent. Gratifyingly, use of scant
amount of ethanol enhanced the yield of the desired
product remarkably. In the next step, the catalyst amount
was optimized by using various amount of the catalyst
(0.01–0.05 g). It turned out that the higher the amount
of the catalyst, the higher the yield of the product.
However, this was not a sustainable trend and increase
of the catalyst amount further than the optimum value
(0.025 g) had no effect on the yield of the product. Hence,
0.025 g was selected as the best catalyst amount. Finally,
the effect of ultrasonic irradiation on the yield of the prod-
uct was studied. It was found that the yield of the product
was markedly dependent on the power of ultrasonic irradi-
ation. Upon using low power (30 W), the reaction did not
proceed efficiently and low yield of the product was
obtained. Increase of the power of ultrasonic irradiation
to 80 W dramatically enhanced the yield of the product.
However, further increase to 100 W had a detrimental
effect and the yield of the desired product decreased. This
observation was attributed to the side‐reactions; induce
by high ultrasonic power that led to the formation of
by‐products. The results established that using 0.025 g of
the catalyst, the mixture of water: ethanol and ultrasonic
power of 100 W were the optimum reaction variables.
Having the optimum reaction conditions in hand, we
investigated the generality of the protocol by using
various isatines, cyanoacetic esters or malononitrile and
1,3‐dicarbonyl compounds (Table 3).
The results established that using various isatines,
cyanoacetic esters or malononitrile and 1,3‐dicarbonyl
compounds led to the corresponding products in high
yields. However, the use of isatin with electron withdraw-
ing group led to the desired product in shorter reaction
time. Moreover, compared to 4‐hydroxycoumarin, use of
dimedone resulted in shorter reaction times. These results
showed that the electron density of the substrate can
affect the yield of the product.
TABLE 1 Textural properties of the HPA@HNTs‐IMI‐SO3H and
pure HNTs
SBET
Average pore Total pore
Sample
(m2 g−1) diameter (nm) volume (cm3 g−1
)
HPA@HNTs‐
IMI‐SO3H
99
51
36
15
0.8
0.2
In the next step, the efficiency of the present protocol,
i.e. using HPA@HNTs‐IMI‐SO3H catalyst and ultrasonic
irradiation, for promoting of the reaction of 4‐
HNTs

8 of 12
SADJADI ET AL.
TABLE 2 Effects of loading of catalyst, duration of reaction and solvent on the yield of model product via model reactiona
Entry
Catalyst (g)
Condition Solvent/ temperature (°C)/ power (W)
Time (min)
Yield (%)b
1
6
H2O/EtOH: 8/2 / r.t./ 80
120
Trace
2
0.01
H2O/EtOH: 8/2 / r.t./ 80
H2O/EtOH: 8/2 / r.t./ 80
H2O/EtOH: 8/2 / r.t./ 80
H2O/EtOH: 8/2 / r.t./ 30
H2O/EtOH: 8/2 / r.t./ 100
H2O/EtOH: 8/2 / 50/ 80
Water/ r.t. / 80
15
15
15
15
15
15
15
15
15
15
15
55
95
95
30
80
85
75
60
50
40
80
3
0.025
0.05
4
5
0.025
0.025
0.025
0.025
0.025
0.025
0.025
0.025
6
7
8
9
EtOH/ r.t./ 80
10
11
12
CH3CN/ r.t./ 80
Toluene/ r.t./ 80
H2O/EtOH: 5/5 / r.t./ 80
aReaction condition: a mixture of isatine 1a (1 mmol), dimedone 2a (1 mmol), malononitrile 3a (1 mmol) and HPA@HNTs‐IMI‐SO3H was reacted by ultrasonic
irradiation.
bIsolated yield.
TABLE 3 Synthesis of spirooxindole catalyzed by HPA@HNTs‐IMI‐SO3Ha
Entry
R1
R2
R3, R4
Time(min)
Yield(%)b
1
1a: H
2a: CN
3a: CH2‐CH(CH3)2‐CH2
5
90
2
1a
2a
3b: CH3
3b
OC2H5
30
55
10
60
30
15
30
90
25
90
90
90
95
85
90
98
70
85
3
1a
2b: CO2Et
3b
3b
4
1b: NO2
1a
2a
2a
2b
2a
2a
2b
2b
3b
5
4a
6
1a
4a
7
1b
3a
8
1b
4a
9
1b
4a
10
1b
3a
aReaction condition: a mixture of isatines (1 mmol), derivatives of malononitrile (1 mmol), 1,3‐dicarbonyles (1 mmol) and HPA@HNTs‐IMI‐SO3H as a catalyst
(0.025 g) in H2O/EtOH (8:2) subjected to ultrasonic irradiation at room temperature and 80 W.
bisolated yields.
hydroxycumarine, malononitrile and 6‐nitroindoline‐2,3‐
dione was compared with some of the previously reported
methodologies, Table 4. As shown in Table 4, this reaction
was performed previously under various conditions
including ultrasonic irradiation, reflux and solvent‐free
condition. Compared to the tabulated reports, the present
protocol led to the desired product in shorter reaction
time. In the case of using piperidine under ultrasonic irra-
diation, the reaction time was comparative. However, the
yield of the product was lower. Additionally, piperidine
was a homogeneous and toxic catalyst. Hence, from the
green chemistry point of view, the catalytic performance
of HPA@HNTs‐IMI‐SO3H was superior to that of
HPA@HNTs‐IMI‐SO3H. Use of L‐proline, EDDA and PPL
resulted in the desired product in comparative yield. How-
ever, all of these three catalysts were homogeneous and
led to the product in longer reaction times. Other
catalysts, exhibited inferior performance in terms of
product yield and reaction time. Besides short reaction
time, low catalyst amount and reusability of the catalyst
are the advantageous of the present protocol.
3.3 | Reaction mechanism
The plausible reaction mechanism is depicted in
Scheme 2. It is postulated that the catalyst could promote

SADJADI ET AL.
9 of 12
TABLE 4 Comparison of the result using our reaction system with results obtained by other published works for spirooxindolea
Entry
Catalyst (amount)
Reaction conditions
Yield (%)
Time (h:Min)
Ref
[1]
1
Carbon‐SO3H (2.5 mol%)
EtOH/ reflux/S.F.
86
05:00
[3]
2
Piperidine (5 mol%)
EtOH/ US/ 50 C
84
94
95
91
94
95
00:07
00:20
01:00
00:15
03:00
00:04
[4]
L‐proline (10%)
H2O/ 80
H2O/ 60
H2O/ 80
̊C
[35]
[36]
[37]
EDDA (10 mol%)b
Nano‐FGT (56 mg)c
PPL (30 mg)d
̊C
̊C
EtOH:H2O/ 30
̊C
3
HPA@HNTs‐IMI‐SO3H (0.025 g)
H2O/EtOH: 8/2 / U.S/ 50
̊
[this work]
aReaction condition: a mixture of 4‐hydroxycumarine (1 mmol), malononitrile (1 mmol.), 6‐nitroindoline‐2,3‐dione (1 mmol) was reacted.
bEthylenediamine diacetate.
cGlutathione grafted nano‐organocatalyst
dLipase from Porcine Pancreas (Anzyme)
SCHEME 2 The plausible mechanism
of synthesis of spirooxindole in the
presence of HPA@HNTs‐IMI‐SO3H
successfully recovered and reused for three successive
reaction runs with only slight loss of the catalytic activity.
Unfortunately, reusing the catalyst for fourth reaction run
resulted in dramatic decrease in the catalytic performance
and the model product was achieved only in 70% yield. To
elucidate the reason of this observation, the FTIR spec-
trum of the reused catalyst for four times was obtained
and compared with that of the fresh catalyst, Figure 8.
Interestingly, the two spectra were distinguished and in
the spectrum of the reused catalyst some extra bands
could be observed. This observation can be attributed to
the deposition of some organic species on the catalyst in
the course of several reaction runs. Moreover, the intensi-
ties of the some characteristic bands were reduced. It is
suggested that using ultrasonic irradiation for four reac-
tion runs can induce the leaching of HPA and conse-
quently the reduction of the catalytic activity. To
confirm this postulation, the HPA leaching was examined
after four reaction runs. It was found that upon reusing
the Knoevenagle condenstion of isatin and malononitrile
or cyanoacetic ester through activation of the carbonyl
group of isatin. The resulting intermediate then reacted
with 1,3‐dicarbonyl compounds to furnish a new interme-
diate which subsequently tolerated.
3.4 | Reusability of the catalyst
Ease of recovery of a heterogeneous catalyst and high
reusability can render the catalyst green and cost‐effec-
tive. Hence, the study of the reusability of the catalyst is
imperative. In this context, the reusability of
HPA@HNTs‐IMI‐SO3H for model reaction was investi-
gated. To this purpose, the model reaction was carried
out in the presence of fresh HPA@HNTs‐IMI‐SO3H.
Upon the completion of the reaction, the catalyst was sim-
ply filtered off, washed and dried (Experimental section)
and reused for consecutive reaction runs. The results,
Figure 7, established that the catalyst could be

10 of 12
SADJADI ET AL.
FIGURE 7 Reusability of the
HPA@HNTs‐IMI‐SO3H catalyst for the
three component reaction
FIGURE 8 The comparison of FTIR
analysis for fresh HPA@HNTs‐IMI‐SO3H
(a) and after 4 runs (b)
the catalyst for four reaction runs the HPA leaching
increased remarkably, justifying the observed lower
catalytic activity.
suspended in the solvent in the absence of the reagent and
subjected to the ultrasonic irradiation for 15 min, the time
required for three reaction runs. Then, the catalyst was
recovered and filtrate was kept for further test. The recov-
ered catalyst was reused for fourth reaction run in the
presence of the reagents. Moreover, the reagents were
added to the filtrate to see whether the leached HPA are
enough to promote the reaction. The results showed that
the reaction could proceed in the filtrate and yield the
desired product to 20% yield, indicating the significant
amount of the leached HPA in the filtrate. The result of
the reused catalyst also showed a decrease in the catalytic
activity and the products were obtained in about 75%
yield, implying the main role of ultrasonic irradiation on
leaching of HPA.
To elucidate whether the loss of the catalytic activity is
mostly induced by the ultrasonic irradiation or acidic and
basic functionalities located on the reactants, we designed
a control experiment in which the catalyst was suspended
in the reaction solvent without any reagents and subjected
to the ultrasonic irradiation. We postulated that if the
ultrasonic irradiation could effectively promote the
leaching of HPA, after several reaction runs the HPA
leached in the filtrate could promote the organic transfor-
mation. Moreover, it is expected that if ultrasonic irradia-
tion had a main role in HPA leaching, the catalyst reused
from the reagent‐less system after several times (forth
run) must exhibit lower catalytic activity, similar to the
one observed for the reused catalyst for four times in the
presence of the reagents. Hence, the catalyst was
For further study, the filtrate was subjected to the ICP
test and the result established the leaching of HPA.
Hence, it can be concluded that loss of the catalytic

SADJADI ET AL.
11 of 12
activity could stem from both ultrasonic irradiation and
the effect of the reagents. However, the effect of the ultra-
sonic irradiation was predominant and more pronounced.
3.5.4 | 2′‐Amino‐5‐nitro‐1,2‐dihydro‐2,5′‐
dioxospiro[3H–indole‐3,4′‐[4H,5H]
pyrano[3,2‐c] [1]benzopyr‐an]‐3′‐
carbonitrile (entry 8)
White solid; m.p. 292–294 °C, IR (KBr) ν cm−1: 3318,
3260, 3187, 2923, 2194, 1717, 1671, 1585, 1467, 1342. H
3.5 | Selected spectral data (Supporting
data)
1
NMR (DMSO‐d6, 400 MHz) δ (ppm): 7.07 (d, J = 8 Hz,
1H), 7.47 (d, J = 8 Hz, 1H), 7.54 (t, J = 8 Hz, 1H), 7.76
(t, J = 8 Hz, 1H), 7.85 (s, NH2), 7.93 (d, J = 8 Hz, 1H),
8.19 (d, J = 8 Hz, 1H), 8.34 (s, 1H), 11.43 (s, 1H, NH),
13C NMR (DMSO‐d6, 100 MHz) δ (ppm): 57.6, 70.5,
101.2, 109.9, 112.9, 117.2, 117.4, 122.5, 123.1, 124.8,
125.7, 129.3, 133.5, 134.1, 142.9, 152.4, 155.9, 155.9,
158.9, 177.6.
3.5.1 | 2‐Amino‐7,7‐dimethyl‐2′,5‐dioxo‐
5,6,7,8‐tetrahydrospiro[chromene‐4,3′‐
indoline]‐3‐carbonitrile (entry 1)
White powder, m.p: 250–252 °C. IR (KBr) ν cm−1: 3296,
1
3196, 2968, 2205, 1712, 1673, 1471. H NMR (DMSO‐d6,
400 MHz) δ (ppm): 1.01 (s, 3H, CH3), 1.04 (s, 3H, CH3),
2.10 (d, J = 16.0 1H, CH2), 2.18 (d, J = 16.0 Hz,
1H, CH2), 2.54 (d, J = 18.0 Hz, 1H, CH2), 2.59
(d, J = 18.0 Hz, 1H, CH2), 6.79 (d, J = 7.6 Hz, 1H, ArH),
6.89 (t, J = 7.2 Hz, 1H, ArH), 6.98 (d, J = 7.2 Hz, 1H,
ArH), 7.14 (t, J = 7.6 Hz, 1H, ArH), 7.24 (s, 2H, NH2),
10.40 (s, 1H, NH). 13C NMR (DMSO‐d6, 100 MHz) δ
(ppm): 27.1, 28.0, 32.3, 47.2, 50.4, 57.9, 109.7, 111.2,
117.7, 122.1, 123.4, 128.5, 134.8, 142.4, 152.4, 159.2,
166.5, 178.5, 195.4.
4 | CONCLUSION
In summary, design and synthesis of the HPA@HNTs‐
IMI‐SO3H through functionalization of halloysite
nanotubes with ionic liquid and incorporation of
heteropolyacid is disclosed. The hybrid system was
successfully used for promoting ultrasonic‐assisted
three‐component reaction of isatines, malononitrile or
cyanoacetic esters and 1,3‐dicarbonyl compounds to fur-
nish the corresponding spirooxindole in short reaction
time and high yields. The ICP‐AES analysis and FTIR
spectroscopy revealed that the catalyst preserved its cata-
lytic activity for three reaction runs while exhibited lower
catalytic activity upon reusing for fourth run. Leaching
test using ICP‐AES demonstrated that the lower catalytic
activity stem from the HPA leaching which can be due
to the ultrasonic irradiation for several reaction runs.
3.5.2 | Ethyl 2′‐Amino‐3′‐cyano‐6′‐methyl‐
2‐oxospiro[indoline‐3,4′‐pyran]‐5′‐carboxyl-
ate (entry 2)
Cream powder, m.p. 260–262 °C, IR (KBr) ν cm−1: 337,
3314, 3140, 2965, 2192, 1723, 1655, 1472. 1H NMR
(DMSO‐d6, 400 MHz) δ (ppm): 0.78 (t, J = 6.8 Hz, 3H,
CH3), 2.32 (s, 3H, CH3), 3.75–3.79 (m, 2H, CH2), 6.80
(d, J = 7.6 Hz, 1H, ArH), 6.93 (t, J = 7.2 Hz, 1H, ArH),
7.06 (d, J = 7.2 Hz, 1H, ArH), 7.15 (s, 2H, NH2), 7.18
(t, J = 7.6 Hz, 1H, ArH), 10.40 (s, 1H, NH). 13C NMR
(DMSO‐d6, 100 MHz) δ (ppm): 13.6, 19.2, 49.6, 57.1,
60.9, 105.3, 110.0, 118.1, 122.5, 124.0, 129.2, 135.2, 142.8,
159.2, 159.6, 165.1, 179.2.
ACKNOWLEDGEMENT
The authors appreciate partial financial supports from
Alzahra University and Iran Polymer and Petrochemical
Institute. MMH is also thankful to Iran National Science
Foundation for the Individual given grant.
3.5.3 | 2′‐Amino‐1,2‐dihydro‐2,5′‐
dioxospiro[3H–indole‐3,4′‐[4H,5H]
pyrano[3,2‐c] [1] benzopyran]‐3′‐
carbonitrile (entry 5)
White solid, m.p. 273–274 °C, IR (KBr) ν cm−1: 3378,
3300, 3199, 2905, 2203, 1673, 1606, 1474, 1417, 1359. H
NMR (DMSO‐d6, 400 MHz) δ (ppm): 6.86 (d, J = 7.6 Hz,
1H, ArH), 6.94 (t, J = 7.6 Hz, 1H, ArH), 7.22 (t,
J = 7.2 Hz, 2H, ArH), 7.49 (d, J = 8.4 Hz, 1H, ArH), 7.54
(t, J = 8.0 Hz, 1H, ArH), 7.68 (s, 2H, NH2), 7.77
(t, J = 8.0 Hz, 1H, ArH), 7.95 (d, J = 7.6 Hz, 1H, ArH),
10.69 (s, 1H, NH).
ORCID
Samahe Sadjadi http://orcid.org/0000-0002-6884-4328
Majid M. Heravi http://orcid.org/0000-0003-2978-1157
1
REFERENCES
[1] B. Maheshwar Rao, G. Niranjan Reddy, T. Vijaikumar Reddy,
B. L. A. Prabhavathi Devi, R. B. N. Prasad, J. S. Yadav, B. V.
Subba Reddy, Tetrahedron Lett. 2013, 54, 2466.
[2] W.‐B. Chen, Z.‐J. Wu, Q.‐L. Pei, L.‐F. Cun, X.‐M. Zhang, W.‐C.
Yuan, Org. Lett. 2010, 12, 3132.

12 of 12
SADJADI ET AL.
[3] S. Golizadeh, K. Radmoghadam, Orient. J. Chem. 2013, 29, 1637.
[23] Y. Zhang, J. Ouyang, H. Yang, Appl. Clay Scie. 2014, 95, 252.
[24] S. Sadjadi, M. M. Heravi, M. Daraie, J. Mol. Liq. 2017, 231, 98.
[25] S. Sadjadi, M. M. Heravi, RSC Adv 2017, In press.
[4] Y. Li, H. Chen, C. Shi, D. Shi, S. Ji, J. Comb. Chem. 2010, 12,
231.
[5] X. H. Chen, Q. Wei, S. W. Luo, H. Xiao, L. Z. Gong, J. Am.
Chem. Soc. 2009, 131, 13819.
[26] M. M. Heravi, E. Hashemi, Y. Shirazi Beheshtiha, S. Ahmadi, T.
Hosseinnejad, J. Mol. Catal. A. 2014, 394, 74.
[6] S. Sadjadi, M. M. Heravi, Curr. Org. Chem. 2016, 20, 1404.
[27] M. M. Heravi, F. Mousavizadeh, N. Ghobadi, M. Tajbakhsh,
[7] L. Hong, Y. Gui, J. Lu, J. Hu, J. Yuan, L. Niu, Int. J. Hydrogen
Energy 2013, 38, 11074.
Tetrahedron Lett. 2014, 55, 1226.
[28] S. Sadjadi, M. M. Heravi, M. Daraie, Res. Chem. Intermed. 2017, 7,
[8] M. M. Heravi, S. Sadjadi, J. Iran. Chem. Soc. 2009, 6, 1.
36807.
[9] T. Fotiou, T. M. Triantis, T. Kaloudis, E. Papaconstantinou, A.
[29] S. Mallik, S. S. Dash, K. M. Parida, B. K. Mohapatra, J. Colloid
Interface Sci. 2006, 300, 237.
Hiskia, J. Photochem. Photobiol., A 2014, 286, 1.
[10] X. Cuixia, Y. Kedi, L. Zili, Q. Zuzeng, H. Wei, D. Qianwen, Z.
[30] H. Zhu, M. L. Du, M. L. Zou, C. S. Xu, Y. Q. Fu, Dalton Trans.
2012, 41, 10465.
Jianjie, Z. Fan, Chin. J. Chem. Eng. 2014, 22, 305.
[11] B. A. Dar, A. K. Sahu, P. Patidar, P. R. Sharma, N. Mupparapu,
D. Vyas, S. Maity, M. Sharma, B. Singh, J. Ind. Eng. Chem. 2013,
19, 407.
[31] S. Bordeepong, D. Bhongsuwan, T. Pungrassami, T.
Bhongsuwan, Songklanakarin J. Sci. Technol 2011, 33, 599.
[32] L. Zatta, J. E. F. da Costa Gardolinski, F. Wypych, Appl. Clay
Scie. 2011, 51, 165.
[12] G. D. Yadav, S. O. Katole, A. K. Dalai, Appl. Catal., A 2014, 477,
18.
[33] S. Kumar‐Krishnan, A. Hernandez‐Rangel, U. Pal, O. Ceballos‐
Sanchez, F. J. Flores‐Ruiz, E. Prokhorov, O. Arias de Fuentes,
R. Esparza, M. Meyyappan, J. Mater. Chem. B 2016, 4, 2553.
[13] P. Yuan, A. Thill, F. Bergaya, Nanosized Tubular Clay Minerals
Halloysite and Imogolite, 2016, 7, 49.
[14] B. Szczepanik, P. Słomkiewicz, Appl. Clay Sci. 2016, 124‐125, 31.
[34] P. Yao, S. Zhong, Z. Shen, Int. J. Photoenergy 2015, (1).
[35] G. S. Hari, Y. R. Lee, Synthesis 2010, 3, 453.
[15] S. Barrientos‐Ramírez, E. V. Ramos‐Fernández, J. Silvestre‐
Albero, A. Sepúlveda‐Escribano, M. M. Pastor‐Blas, A.
González‐Montiel, Microporous Mesoporous Mater. 2009, 120,
132.
[36] R. Jamatia, A. Gupta, A. Kumar Pal, RSC Adv. 2016, 6, 20994.
[37] S.‐J. Chai, Y.‐F. Lai, J.‐C. Xu, H. Zheng, Q. Zhu, P.‐F. Zhang,
Adv. Synth. Catal. 2011, 353, 371.
[16] P. Yuan, P. D. Southon, Z. Liu, M. E. R. Green, J. M. Hook, S. J.
Antill, C. J. Kepert, J. Phys. Chem. C 2008, 112, 15742.
SUPPORTING INFORMATION
[17] Y. Zhang, A. Tang, H. Yang, J. Ouyang, Appl. Clay Sci. 2016,
119, 8.
Additional Supporting Information may be found online
in the supporting information tab for this article.
[18] S. Sadjadi, M. M. Heravi, M. Daraie, Res. Chem. Intermed. 2017,
43, 2201.
[19] D. Grabka, M. Raczyńska‐Żak, K. Czech, P. M. Słomkiewicz, M.
A. Jóźwiak, Appl. Clay Sci. 2015, 114, 321.
How to cite this article: Sadjadi S, Heravi MM,
Malmir M, Masoumi B. HPA decorated Halloysite
Nanoclay: An efficient catalyst for the green
synthesis of Spirooxindole derivatives. Appl
Organometal Chem. 2017;e4113. https://doi.org/
10.1002/aoc.4113
[20] R. S. Murali, M. Padaki, T. Matsuura, M. S. Abdullah, A. F.
Ismail, Sep.Purif.Technol. 2014, 132, 187.
[21] M. Massaro, V. Schembri, V. Campisciano, G. Cavallaro, G.
Lazzara, S. Milioto, R. Noto, F. Parisi, S. Riela, RSC Adv. 2016,
6, 55312.
[22] Y. Zhang, H. Yang, Phys. Chem. Miner. 2012, 39, 789.