Preparation of GO/SiO2/PEA as a new solid base catalyst for the green synthesis of some spirooxindole derivatives

Article abstract of DOI:10.1039/d1ra02850b

Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO₂/PEA) as a solid base catalyst was studied. GO/SiO₂/PEA has been obtained through a two step reaction and characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), thermo gravimetric analysis (TGA), Raman spectroscopy and X-ray diffraction (XRD). Green reaction conditions, short reaction times, reusable catalyst and a high to excellent yield of products are some of the advantageous of the presented method.

Full text of DOI:10.1039/d1ra02850b

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Preparation of GO/SiO2/PEA as a new solid base
catalyst for the green synthesis of some
spirooxindole derivatives†
Cite this: RSC Adv., 2021, 11, 21840
*
Mahla Toorbaf and Leila Moradi
Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of
graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO2/PEA) as a solid base catalyst was
studied. GO/SiO2/PEA has been obtained through a two step reaction and characterized by Fourier
transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), energy-
dispersive X-ray spectroscopy (EDX), thermo gravimetric analysis (TGA), Raman spectroscopy and X-ray
diffraction (XRD). Green reaction conditions, short reaction times, reusable catalyst and a high to
excellent yield of products are some of the advantageous of the presented method.
Received 12th April 2021
Accepted 7th June 2021
DOI: 10.1039/d1ra02850b
rsc.li/rsc-advances
activities of these molecules have been demonstrated9–12 there-
fore; it is desirable to develop simple and highly efficient
Introduction
methods for the preparation of spiroxindoles. Some of catalysts
for synthesis of these compounds are include: piperidin13,
Et3N,14 MNPs-guanidne,15 Na2CaP2O7,16 L-proline,17 meglu-
mine,18 SnO2 (ref. 19) and CuO nanoparticles20 and also 4-
dimethylaminopyridine.21
In recent years, supported catalysts as green and reusable
catalysts have received much attention in the design of chem-
ical syntheses. Graphene oxide (GO) and reduced graphene
oxide has been used as catalyst support due to high surface area,
easily available, low cast and high activity.22–24 Graphene is
a two-dimensional sheet of carbon atoms in a hexagonal
conguration in which atoms are bonded to the sp2 hybrid. This
structure is the newest member of the multi dimensional
graphite carbon family.25,26 Graphene oxide is a nanocarbon
material with a honeycomb-like carbon plate which has
epoxide, hydroxyl and carboxyl functional groups on its
surfaces.
In presented method, we try to design a new heterogeneous
catalyst based on graphene oxide. In fact, an amino group has
been chemically attached on graphene oxide surfaces through
SiO2 linker. Obtained basic catalyst was used in green synthesis
of some spirooxindoles (Scheme 1). Results show the high
efficiency of catalyst as well as short reaction times with high to
excellent yield of products.
Multicomponent reactions (MCRs) allow quick and easy access
to a large group of organic compounds.1–3 Three or more reac-
tants reacted to form the products consisting of all raw mate-
rials.4 Because these reactions do not require intermediate
separation, their efficiency increases dramatically. Simple
conditions, reduction of byproducts, easy separation, energy
saving and short reaction times are the benets of these
reactions.5
Recently, green approaches in designing the synthetic
methods have attracted considerable attention. Green chem-
istry means the design of chemical products and processes that
reduce or eliminate the use and production of harmful
substances to human health and the environment. The goals of
this approach are the implementation and sustainable devel-
opment of chemistry and technology in the chemical industry,
academia and government.6 Green chemistry is usually pre-
sented as a set of twelve principles suggested by Anastas and
Warner, including guidelines for the chemists that work on the
synthesis of materials, new chemicals, and new technological
processes.7,8
Spiroxindoles as a kind of polycyclic compounds, play an
important role in the medical elds. Different derivatives of
spiroxindoles are seriously on the agenda of scientists. On the
other hand, with the change of precursors and methods of
preparation of these compounds, new features of them are
revealed in the medical and pharmaceutical elds. The anti-
bacterial, anticancer, antitumour, antifungal and antimicrobial
Experimental section
Materials and methods
Chemical reagents were purchased from the Merck and Aldrich
Company. FT-IR spectra were obtained using KBr pellets on
a Perkin Elmer 781 spectrophotometer and on an impact 400
Nicolet FTIR spectrophotometer. 1H NMR and 13C NMR spectra
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, P.O.
Box 8731753153, Kashan, I. R. Iran. E-mail: l_moradi@kashanu.ac.ir
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d1ra02850b
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Scheme 1 Synthesis of spirooxindoles in the presence of GO/SiO2/PEA.
were measured with DMSO-d6 solution and tetramethylsilane as
internal standard on a Bruker DRX-400 spectrometer. Thermo
gravimetric analysis (TGA) was performed on a mettle TA4000
system TG-50 at a heating rate of 10 K minꢀ1 under N2 atmo-
sphere. Raman spectroscopy was provided using FRA/106/S. To
investigate the morphology of the MWCNTs and prepared
catalyst, FE-SEM images and EDX analysis visualized by a Sigma
ZEISS, Oxford Instruments Field Emission Scanning Electron
Microscope. TEM images was provided using a Philips CM 120,
Netherlands microscope with an accelerating voltage of 150 kV.
Preparation of graphene oxide functionalized with 2-(1-
piperazinyl) ethylamine (GO/SiO2/PEA)
In a balloon equipped with a magnetic stirrer and a nitrogen gas
conduction system, 1 g of graphene oxide, 100 ml of dry toluene
and 1 ml of (3-chloropropyl) triethoxyethane were mixed and
reuxed at 60 ꢁC for 18 h. Aer the completion of this step, the
content of the balloon was ltered and obtained solid (GO/
CPTES) washed with EtOH and dried at 80 ꢁC for 16 hours.28
For preparation of GO/SiO2/PEA, 0.5 g of GO/CPTES was
dispersed in 15 ml of dry toluene for 10 min by ultrasonication.
Then 0.5 ml of 2-(1-piperazinyl) ethylamine (PEA) was added to
the mixture and reuxed for 28 hours. Aer the time had
elapsed, the mixture was ltered and the nal product was
Preparation of graphene oxide (GO)
GO was synthesized from graphite using the Hummers
method.27 Briey in a typical procedure, 1 g graphite, 15 ml
H3PO4 and 135 ml H2SO4 were mixed. 6.6 g KMnO4 was slowly
added while stirring, and the rate of addition was controlled to
ꢁ
washed with ethanol and dried at 80 C for 12 h (Scheme 2).
General procedure for the preparation of spiro derivatives
prevent the mixture temperature exceeding from 5 ꢁC. Then, to For the synthesis of spiro [indulin-3,40-pyrano[2,3-c]pyrazole]-50-
remove the excess amounts of KMnO4, 3.5 ml of H2O2 was carbonitrile derivatives (5a–e), a mixture of ethyl acetoacetate (1
slowly added and stirred for 10 minutes. Aer le the mixture to mmol) and hydrazine hydrate (1 mmol) were stirred by
ꢁ
cool down, 25 ml of HCl and 15 ml of (deionized water) DI water magnetic stirrer in 5 ml of water for 15 minutes at 60 C. Aer
was added and centrifuged. The supernatant was decanted and the formation of 3-methyl-2-pyrazoline-5-one as
a white
the residuals was then rewashed again with HCl and DI water precipitate, isatin (1 mmol) and malononitrile (1 mmol) and
forꢁ3 times and centrifuged. Obtained washed GO was dried at also catalyst (0.015 g) were added and reaction was continued to
90 C for 24 hours to produce the powder of GO.
complete (followed by thin-layer chromatography). Aer the
Scheme 2 Preparation of GO/SiO2/PEA catalyst.
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reaction was completed, the precipitate was dissolved in 12.40 (1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-d6) dC: 9.8,
ethanol and the catalyst was separated by ltration. Evaporation 48.3, 55.4, 95.2, 110.8, 119.8, 121.6, 127.3, 134.6, 136.5, 144.5,
of solvent from the ltrate, resulted the crud product and for 148.9, 156.7, 164.1, 178.9 ppm; anal. calcd for C15H10N6O4: C,
further purication, recrystallized from ethanol (Scheme 1).
53.25; H, 2.96; N, 24.85%. Found: C, 53.22; H, 3.12; N, 24.79%.
In order to the synthesis of 7-amino-2,4-dihydro [indoline-
60-Amino-30-methyl-2-oxo-10H-spiro[5-uoro-indoline-3,40-
3,5-pyrano(2,3-d)pyrimidine]-6-carbonitriles (6a–g), a mixture of pyrano[2,3-c]pyrazole]-50 carbonitrile (5c). Mp 262–265 ꢁC. FTIR
isatin (1 mmol), malononitrile (1 mmol) and barbituric acid (KBr) nmax: 3409 (NH), 3220 (NH), 2186 (C]N), 1706 (C]O),
derivative (1 mmol) in the presence of 0.015 g of catalyst and 1490 (C–H, Ar) cmꢀ1 1H NMR (400 MHz, DMSO-d6) dH: 1.56
;
5 ml of water was stirred by magnetic stirrer at 60 ꢁC for 18 min. (3H, s, CH3), 6.90 (1H, s, ArH), 6.97 (1H, d, J ¼ 6.0 Hz, ArH), 7.07
Aer the completion of reaction was complete, the separation (1H, d, J ¼ 7.0 Hz, ArH), 7.28 (2H, s, NH2), 10.62 (1H, s, NH),
and purication of products was the same as previous synthetic 12.31 (1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-d6) dC: 9.4,
method.
48.3, 55.3, 95.4, 111.0, 116.2, 119.1, 134.9, 135.2, 138.3, 147.6,
155.8, 157.8, 163.3, 178.2 ppm; anal. calcd for C15H10FN5O2: C,
57.82; H, 3.21; N, 22.49%. Found: C, 57.79; H, 3.23; N, 22.51%.
60-Amino-30-methyl-2-oxo-10H-spiro[5-chloro-indoline-3,40-
pyrano[2,3-c]pyrazole]-50-carbonitrile (5d). Mp 232–234 ꢁC. FTIR
(KBr) nmax: 3346 (NH), 3137 (NH), 2182 (C]N), 1714 (C]O),
Spectral data
60-Amino-30-methyl-2-oxo-10H-spiro[indoline-3,40-pyrano[2,3-
c]pyrazole]-50-carbonitrile (5a). Mp 232–234 ꢁC. FTIR (KBr) nmax
3337 (NH), 3132 (NH), 2182 (C]N), 1711 (C]O), 1496 (C–H, Ar)
cmꢀ1; 1H NMR (400 MHz, DMSO-d6) dH: 1.51 (3H, s, CH3), 6.88
(1H, d, J ¼ 7.0 Hz, ArH), 6.96 (2H, m, ArH), 7.22 (2H, s, NH2),
:
1487 (C–H, Ar) cmꢀ1 1H NMR (400 MHz, DMSO-d6) dH: 1.57
;
(3H, s, CH3), 6.90 (1H, d, J ¼ 6.0 Hz, ArH), 7.12 (1H, d, J ¼ 7.0 Hz,
ArH), 7.29 (1H, s, ArH), 7.29 (2H, s, NH2), 10.74 (1H, s, NH),
12.33 (1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-d6) dC: 9.4,
48.1, 55.1, 95.2, 112.0, 119.1, 125.1, 127.1, 129.5, 135.6, 141.3,
155.7, 163.3, 177.9 ppm; anal. calcd for C15H10ClN5O2: C, 54.88;
H, 3.05; N, 21.34%. Found: C, 54.89; H, 3.09; N, 21.41%.
60-Amino-30-methyl-2-oxo-10H-spiro[5-bromo-indoline-3,40-
pyrano[2,3-c]pyrazole]-50-carbonitrile (5e). Mp 248–250 ꢁC. FTIR
(KBr) nmax: 3346 (NH), 3141 (NH), 2182 (C]N), 1713 (C]O),
7.24 (1H, s, ArH), 10.59 (1H, s, NH), 12.27 (1H, s, NH) ppm; 13
C
NMR (100 MHz, DMSO-d6) d: 12.5, 47.1, 58.5, 111.1, 112.5,
116.2, 122.1, 125.6, 127.7, 140.7, 162.6, 166.9, 175.3 ppm. Anal.
calcd for C15H11N5O2: C, 61.43; H, 3.78; N, 23.88%. Found: C,
61.36; H, 3.75; N, 23.82%.
60-Amino-30-methyl-2-oxo-10H-spiro[5-nitro-indoline-3,40-pyr-
ano[2,3-c]pyrazole]-50-carbonitrile (5b). Mp 226–228 ꢁC. FTIR
(KBr) nmax: 3419–3337 (NH), 3174 (NH), 2187 (C]N), 1720 (C]
O), 1498 (C–H, Ar) cmꢀ1; 1H NMR (400 MHz, DMSO-d6) dH: 1.57
(3H, s, CH3), 7.12 (1H, d, J ¼ 7.0 Hz, ArH), 7.41 (2H, s, NH2), 7.90
(1H, s, ArH), 8.21 (1H, d, J ¼ 8.0 Hz, ArH), 11.36 (1H, s, NH),
1498 (C–H, Ar) cmꢀ1 1H NMR (400 MHz, DMSO-d6) dH: 1.56
;
(3H, s, CH3), 6.86 (1H, d, J ¼ 6.0 Hz, ArH), 7.22 (1H, s, ArH), 7.30
(2H, s, NH2), 7.41 (1H, d, J ¼ 7.0 Hz, ArH), 10.76 (1H, s, NH),
Fig. 1 FT-IR of: (a) GO, (b) GO/SiO2/PEA.
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12.34 (1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-d6) dC: 9.4, 1681 (C]O amide), 1222 (C]O), 1476 (C]C), 1302–1172 (C–
48.0, 55.0, 95.2, 112.2, 114.7, 119.5, 128.0, 132.2, 135.2, 135.5, O) cmꢀ1
;
1H NMR (400 MHz, DMSO-d6) dH: 6.77 (1H, d, J ¼
141.3, 155.6, 163.1, 178.2 ppm; anal. calcd for C15H10BrN5O2: C, 6.0 Hz, ArH), 7.19 (1H, d, J ¼ 7.0 Hz, ArH), 7.36 (1H, s, ArH), 7.45
48.41; H, 2.71; N, 18.82%. Found: C, 48.44; H, 2.65; N, 18.74%. (2H s, NH2), 10.63 (1H, s, NH), 12.39 (1H, s, NH) ppm; 13C NMR
70-Amino-2,40-dioxo-20-thioxo-10,20,30,40-tetrahydrospiro
(100 MHz, DMSO-d6) dC: 48.3, 56.8, 91.0, 110.8, 116.9, 124.4,
[indoline-3,50-pyrano[2,3-d]pyrimidine]-60-carbonitrile (6a). Mp 126.1, 128.6, 135.2, 141.1, 153.3, 158.3, 160.1, 174.3, 177.1 ppm;
281–283 ꢁC. FTIR (KBr) nmax: 3321 (NH2), 2197 (C]N), 1679 (C] anal. calcd for C15H8ClN5O3S: C, 48.15; H, 2.14; N, 18.72%.
O amide), 1249 (C]O) cmꢀ1; 1H NMR (400 MHz, DMSO-d6) dH: Found: C, 48.14; H, 2.18; N, 18.81%.
6.77(1H, d, J ¼ 6.0 Hz, ArH), 6.88 (1H, t, J ¼ 6.0 Hz ArH), 7.16
70-Amino-5-bromo-1,10,2,20,30,40-hexahydro-2,40-dioxo-20-thi-
(2H, t, J ¼ 7.0 Hz, ArH), 7.45 (2H s, NH2), 10.56 (1H, s, NH), 12.51 oxospiro[indole-3,50-pyrano[2,3-d]pyrimidine]-60-carbonitrile
(1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-d6) dc: 45.1, 57.5, (6d). Mp 238–240 ꢁC. FTIR (KBr) nmax: 3350 (NH2), 2199 (C]N),
85.2, 112.4, 119.6, 123.7, 124.3, 129.1, 133.7, 142.6, 163.9, 166.1, 1691 (C]O amide), 1213 (C]O), 1339–1169 (C–O) cmꢀ1 1H
;
167.9, 176.6, 183.2 ppm; anal. calcd for C15H9N5O2S: C, 45.79; NMR (400 MHz, DMSO-d6) dH: 6.74 (1H, d, J ¼ 6.0 Hz, ArH), 7.32
H, 2.29; N, 17.81%. Found: C, 45.81; H, 2.27; N, 17.92%.
(1H, t, J ¼ 7.0 Hz, ArH), 7.50 (1H, s, ArH), 7.50 (2H s, NH2), 10.68
70-Amino-5-uoro-1,10,2,20,30,40-hexahydro-2,40-dioxo-20-thio- (1H, s, NH), 12.54 (1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-
xospiro[indole-3,50ꢁ-pyrano[2,3-d]pyrimidine]-60-carbonitrile
d6) dC: 47.3, 57.3, 91.5, 111.7, 114.1, 117.3, 127.5, 131.8, 137.1,
(6b). Mp 299–301 C. FTIR (KBr) nmax: 3367 (NH2), 3163 (NH), 142.5, 153.8, 158.8, 160.0, 174.8, 177.5 ppm; anal. calcd for
2199 (C]N), 1684 (C]O amide), 1258 (C]O), 1485 (C]C),
C
15H8BrN5O3S: C, 43.06; H, 1.91; N, 16.74%. Found: C, 43.11; H,
1
1184–1341 (C–O) cmꢀ1; H NMR (400 MHz, DMSO-d6) dH: 6.76 1.89; N, 16.69%.
(1H, t, J ¼ 6.0 Hz ArH), 6.95 (1H, t, J ¼ 6.0 Hz, ArH), 7.18 (1H, d, J
2-Amino-6,8-dimethyl-5,7-dioxospiro[50-chloro-(30H)-indol-
¼ 7.0 Hz, ArH), 7.44 (2H s, NH2), 10.53 (1H, s, NH), 12.40 (1H, s, 30,4,4(H)-5,6,7,8-tetrahydropyrano(2,3-d)pyrimidine]-(10H)-20-
NH) ppm; 13C NMR (100 MHz, DMSO-d6) dC: 47.1, 57.0, 91.2, one-3-carbonitrile (6e). Mp 248–250 ꢁC. FTIR (KBr) nmax: 3407
110.0, 112.3, 115.1, 116.8, 134.7, 138.4, 152.9, 157.1, 158.2, (NH2), 2197 (C]N), 1681 (C]O amide), 1245 (C]O), 1499 (C]
159.2, 174.1, 177.4 ppm; anal. calcd for C15H8FN5O3S: C, 50.42; C), 1302–1172 (C–O) cmꢀ1; H NMR (400 MHz, DMSO-d6) dH:
1
H, 2.24; N, 19.61%. Found: C, 50.44; H, 2.22; N, 19.59%.
3.02 (3H, s, CH3), 3.35 (3H, s, CH3), 6.79 (1H, d, J ¼ 6.0 Hz, ArH),
70-Amino-5-chloro-1,10,2,20,30,40-hexahydro-2,40-dioxo-20-thio- 7.18 (1H, d, J ¼ 7.0 Hz, ArH), 7.27 (1H s, ArH), 7.64 (2H, s, NH2),
xospiro[indole-3,50-pyrano[2,3-d]pyrimidine]-60-carbonitrile
(6c). Mp 289–291 ꢁC. FTIR (KBr) nmax: 3357 (NH2), 2197 (C]N), 29.7, 48.1, 56.9, 86.1, 113.5, 117.2, 118.0, 126.4, 130.6, 136.3,
10.63 (1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-d6) dc: 28.2,
Fig. 2 XRD patterns of (a) graphite, (b) GO and (c) GO/SiO2/PEA.
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Fig. 3 TGA curve of: (a) GO and (b) GO/SiO2/PEA.
2-Amino-6,8-dimethyl-5,7-dioxospiro[50-uoro-(30H)-indol-
30,4,4(H)-5,6,7,8-tetrahydropyrano(2,3-d)pyrimidine]-(10H)-20-
one-3-carbonitrile (6f). Mp 276–278 ꢁC. FTIR (KBr) nmax: 3484
140.6, 151.1, 152.6, 157.9, 165.9, 178.1 ppm; anal. calcd for
C
17H12ClN5O4: C, 31.10; H, 3.11; N, 18.13%. Found: C, 31.12; H,
3.09; N, 18.15%.
Fig. 4 FE-SEM (a), EDX (b) and TEM images (c and d) of GO/SiO2/PEA.
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Fig. 5 Raman spectra of GO and GO/SiO2/PEA.
70-Amino-1,10,2,20,30,40-hexahydro-10,30-dimethyl-2,20,40-triox-
(NH2), 2197 (C]N), 1681 (C]O amide), 1288 (C]O), 1486 (C]
1
C) cmꢀ1; H NMR (400 MHz, DMSO-d6) dH: 3.01 (3H, s, CH3),
ospiro[indole-3,50-pyrano[2,3-d]pyrimidine]-60-carbonitrile (6g).
ꢁ
3.46 (3H, s, CH3), 6.77 (1H, m, ArH), 6.97 (1H, t, J ¼ 6.0 Hz ArH),
7.07 (1H, s, ArH), 7.62 (2H, s, NH2), 10.52 (1H, s, NH), 12.50
(1H, s, NH) ppm; 13C NMR (100 MHz, DMSO-d6) dC: 28.2, 30.1,
47.8, 56.9, 85.4, 87.1, 112.3, 117.2, 132.6, 136.9, 137.5, 142.3,
150.1, 153.1, 159.1, 161.0, 178.3 ppm; anal. calcd for
Mp 299–301 C. FTIR (KBr) nmax: 3428 (NH2), 3317 (NH), 2924
1
(CH2), 2000 (C]N), 1693 (C]O amide), 1652 (C]O) cmꢀ1; H
NMR (400 MHz, DMSO-d6) dH: 3.01 (3H, s, CH3), 3.71 (3H, s,
CH3), 6.95 (1H, d, J ¼ 6.0 Hz ArH). 7.28 (2H, t, J ¼ 7.0 Hz, ArH),
7.43 (1H, t, J ¼ 7.0 Hz, ArH), 7.13 (2H, s, NH2) ppm; 13C NMR
(100 MHz, DMSO-d6) dC: 27.4, 29.6, 48.0, 57.5, 87.3, 109.6, 117.0,
121.8, 123.9, 128.4, 133.5, 142.2, 150.0, 152.1, 158.3, 159.2,
177.5 ppm; anal. calcd for C17H13N5O4: C, 34.16; H, 3.70; N,
19.94%. Found: C, 43.14; H, 3.73; N, 19.97%.
C
17H12FN5O4: C, 32.49; H, 3.24; N, 18.95%. Found: C, 32.46; H,
3.28; N, 18.91%.
Table 1 Optimization of solvent and temperature for the synthesis of
spirooxindolesa
Results and discussions
Characterization of catalyst
We have established that GO/SiO2/PEA is an efficient, reusable
and heterogeneous solid base catalyst for the synthesis of spi-
rooxindole derivatives. Presented method has several advan-
tages including excellent yield of products, green reaction
Entry
Solvent
T (ꢁC)
Time (min)
Yieldb (%)
Table
2 Optimization of catalyst amount for the synthesis of
spirooxindolesa
1
2
3
4
5
6
7
8
H2O
H2O
C2H5OH
C2H5OH
C2H5OH/H2O (1 : 1)
C2H5OH/H2O (1 : 1)
CH3CN
r.t.
60
r.t
60
r.t.
60
r.t
60
25
18
25
25
25
25
25
25
80
90
72
83
78
82
12
18
Entry
Catalyst (g)
Time (min)
Yield (%)
1
2
3
4
5
0.005
0.01
0.015
0.018
0.02
30
23
18
18
18
78
84
90
90
90
CH3CN
a
Ethyl acetoacetate (1 mmol), hydrazine hydrate (1 mmol), isatin (1
mmol) and malononitrile (1 mmol) in the presence of 0.015 g of
catalyst. b Isolated yield.
a
(1 mmol) ethyl acetoacetate, (1 mmol) hydrazine hydrate, (1 mmol)
isatin, (1 mmol) malononitrile at 60 ꢁC.
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Table 3 Synthesis of some spirooxindole derivatives using GO/SiO2/PEA
Entry
Carbonyl compound
Isatin
Product
Yield (%)
Mp (ꢁC)
1
90
232–234 (ref. 28)
2
3
92
90
226–228 (ref. 28)
262–265 (ref. 27)
4
5
89
90
232–234 (ref. 27)
248–250 (ref. 27)
6
7
90
93
281–283 (ref. 39)
299–301 (ref. 39)
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Table 3 (Contd.)
Entry
8
Carbonyl compound
Isatin
Product
Yield (%)
Mp (ꢁC)
92
289–291 (ref. 39)
9
91
89
238–240 (ref. 39)
248–250 (ref. 33)
10
11
12
90
90
276–278
299–301 (ref. 20)
conditions, reusability of catalyst and the simple work-up
process. Prepared catalyst was characterized using various PEA. The XRD pattern of graphite shows a sharp and long peak
methods.
at about 26.5ꢁ (with the intermolecular distance of 0.34 nm).
Fig. 2 shows the XRD patterns of graphite, GO and GO/SiO2/
Fig. 1a and b shows the FTIR spectra of GO and GO/SiO2/ Aer the Hummer process and graphene oxide formation, the
PEA. In the FT-IR spectrum, of graphene oxide, the peak at peak is removed and one peak at about 12.7ꢁ was appeared (the
1578 cmꢀ1 corresponds to carbon–carbon double bonds. The interlayer distance become 0.7 nm). In the XRD pattern of the
absorption peaks in the 1057, 1678 and 3437 cmꢀ1 are related to GO/SiO2/PEA, two signals are observed at 2q ¼ 10.8ꢁ, which is
the vibration of C–O, carbonyl and hydroxyl groups, respec- due to the structure of the graphene oxide substrate, and the
tively. In the FT-IR spectra of GO/SiO2/PEA, vibration peaks second widespread signal at 2q ¼ 22.8ꢁ, indicates that the
corresponding to C]O, C]C, Si–O–C and N–H are at 1109, prepared catalyst has a layered structure contains amine
1459, 1628, and 3437 cmꢀ1 demonstrated that the chemically groups.29
attachment of PEA on GO surfaces was done through SiO2
linker.
TGA analysis was used to determine the stability of catalyst
and percentage of functional groups attached on graphene
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oxide surfaces. Fig. 3 exhibited the TGA thermograms of GO and intensity ratio IG/ID for both GO and GO/SiO2/PEA are found to
GO/SiO2/PEA. As can be seen in Fig. 3a, TGA curve of GO is be around 0.39 indicating similar degrees of disorder which is
stable to 220 ꢁC. A major weight loss (about 35%) between understandable considering that functionalization of GO
ꢁ
ꢁ
220 C to 350 C is due to the decomposition of water and the occurs by attachment of SiO2/PEA predominantly on the defect
labile oxygen-containing functional groups on the GO.30 As sites where oxidizing groups were already present and hence it
shown in TGA curve of GO/SiO2/PEA (Fig. 3b), the weight loss does not generally involve conversion of sp2 bonds into sp3.38
ꢁ
about 5% between 20–120 C is assigned to removal of physi-
Aer preparation and characterization of catalyst, to opti-
cally adsorbed water. The second weight loss (about 20%) occur mize the reaction conditions (catalyst amounts, temperature
at the temperatures ranging from 120 to 330 ꢁC, and it is and solvent), the reaction between ethyl acetoacetate (1 mmol),
attributed to the removal of chemically graing of SiO2/PEA on hydrazine hydrate (1 mmol), isatin (1 mmol) and malononitrile
to the GO surfaces (Fig. 3b).31
(1 mmol) was used as model reaction. Firstly, optimization of
In addition, the morphology of prepared catalyst was inves- solvent and temperature was studied. Based on the results
tigated by the FE-SEM and TEM techniques. As can be seen, the depicted in Table 1, it is founded that water is the best solvent in
layered, wrinkled and folded structure of catalyst (in Fig. 4a, c terms of yield and time of reaction (at 60 ꢁC) compared to other
and d) proved that SiO2/PEA chemically attached on the GO solvents.
surfaces.32,33 Also, EDX was used to prove the composition of
GO/SiO2/PEA. Results show the presence of nitrogen, silicon,
carbon and oxygen in catalyst structure to demonstrate the
successfully preparation of GO/SiO2/PEA.
Raman spectroscopy is a nondestructive technique to char-
acterize the structure of carbon based materials. Fig. 5 shows
Raman spectra of GO (curve a) and GO/SiO2/PEA (curve b). For
carbon materials, the main attributes for a Raman spectra is
identied by the D and G bands present around 1345 cmꢀ1 and
1571 cmꢀ1
.
The D band, generated by the zone boundary
34,35
phonons, provides information about the defects and impuri-
ties and the G band arises from the doubly degenerate zone
centre E2g mode and is present for all carbon based mate-
rials.34,36 Fig. 4 also shows that the position of the G band is
shied from 1571 to 1564 cmꢀ1 for GO/SiO2/PEA. This is
consistent with the restoration of sp2 graphitic network.37 The
Fig. 6 Investigation of catalyst reusability.
Scheme 3 Proposed reaction pathway for the synthesis of spirooxindoles.
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Table 4 Comparison of the performance of synthesized catalystsa
Entry
Catalyst
Time
Yield (%)
Reference
1
2
3
4
5
6
7
8
Piperidin
Et3N
Na2CaP2O7
L-Proline
Carbon–SO3H
Meglumine
5 h
5 h
89
80
78
92
90
92
84
80
90
87
90
89
85
83
78
79
90c
13
14
16
17
40
18
41
42
43
44
45
46
47
48
49
50
50 min
30 min
30 min
35 min
4 h
15 min
210 min
5 h
THAMb in ethanol, r.t.
SBA-Pr-NH2, r.t., solvent-free
Chitosan, r.t., (bmim)OH
EDDF–PEG60, r.t.
9
10
11
12
14
15
16
17
18
Ionic liquid/K2CO3 in water
CoFe2O4@SiO2@PUF@Zn(OAc)2 in water
Fe2O3@SiO2@vitB1Np in water for sonication
In water at 6 ꢁC
1 h
45 min
10 min
30 min
20 min
2 min
18 min
g-Fe2O3@HAp-Si(CH2)3SO3H in water at 30 ꢁC
Et3N microwave irradiation
GO/SiO2/PEA
This work
a
Entry 1–10: reaction conditions for the synthesis of 5a and 11–18 for 6a. b Tris-hydroxymethylaminomethane. c The yield of 5a.
Additionally, the optimization of catalyst amount and its
The efficiency of GO/SiO2/PEA was compared with some of
effect on the reaction time and yield was investigated. The data the other catalysts applied for the synthesis of two kinds of
in Table 2 show that 0.015 g of catalyst cause to the best yield of spirooxindole derivatives (5a and 6a). As shown in Table 4, when
product and also the further amount of catalyst did not increase the reaction was performed in the presence of GO/SiO2/PEA in
the yield of product.
water, the reaction time was shorter and the product yield was
Aer the optimization of reaction conditions, for evaluation higher than others. Green reaction conditions contain to reus-
of catalyst efficiency, a variety of spirooxindoles were synthe- able and efficient catalyst, short reaction time, low temperature
sized at optimum conditions. The results and details were as well as easy and clean workup, make this method as a green
summarized in Table 3. As shown in this table, good to excellent and eco-friendly protocol.
yields were achieved aer short reaction times in all cases.
A proposed mechanism for the synthesis of spirooxindoles in
the presence of GO/SiO2/PEA is displayed in Scheme 3. As can be
Conclusion
seen, rstly hydrazine hydrate reacts with ethyl acetoacetate to form We have established that GO/SiO2/PEA is a robust, reusable and
3-methyl-2-pyrazoline-5-one (I). On the other hand, Knoevenagel heterogeneous solid catalyst for the synthesis of spirooxindoles
condensation of malononitrile and isatin in the presence of catalyst, in water under thermal conditions. This method has several
lead to formation of intermediate (II). In the next step, Michael advantages, including excellent yields of products, green reac-
addition occurs between intermediate I and II to produce interme- tion solvent, reusability of catalyst and simple work-up process.
diate (III). Finally, the intramolecular cyclization follow by tauto-
merization of intermediate III resulted the mentioned product.32,33
Conflicts of interest
In order to study on the performance and recyclability of
catalyst, aer the completion of sample reaction, catalyst was There are no conicts to declare.
separated, washed with ethanol and water and dried for using
in other similar reaction. Fig. 6 shows that recycled catalyst
could be reused ve times without considerable decrease in the
Acknowledgements
yield of product to demonstrate the high efficiency and reus- Research Council of Kashan University should be appreciated
ability of GO/SiO2/PEA.
for supporting of this work.
Hot ltration test has been done to detect the catalyst nature
(homogeneous or heterogeneous). In this way, model reaction
was performed under optimized conditions. During the test,
catalyst was separated from the reaction mixture by ltration
aer 9 min (half time of reaction), and the reaction of ltrate
was continued for other 9 min. The yield of product (about 40%)
shown that aer removal of the catalyst, the reaction did not
proceed; indicating that no catalytically active species (amino
groups) remained in the ltrate and the reaction was performed
in the presence of heterogeneous GO/SiO2/PEA catalyst.
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