Guanidine functionalized core-shell structured magnetic cobalt-ferrite: An efficient nanocatalyst for sonochemical synthesis of spirooxindoles in water

Article abstract of DOI:10.1039/d1ra00967b

Core/shell nanoparticles have a wide range of applications in the science of chemistry and biomedicine. The core-shell material can be different and modified by changing the ingredients or the ratio of core to the shell. In this research, a CoFe2O4@SiO2-guanidine nanocomposite was prepared and identified as an efficient catalyst for the one-pot synthesis of spirooxindole derivatives in water under ultrasonic irradiation conditions. The advantages of this method are in its simplicity, saving costs and energy, high yields, short reaction times, environmental friendliness, reusability and easy recovery of the catalyst using an external magnet. The catalyst was characterized by XRD, SEM, TEM, EDX, FT-IR, TGA and VSM techniques.

Full text of DOI:10.1039/d1ra00967b

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Guanidine functionalized core–shell structured
magnetic cobalt-ferrite: an efficient nanocatalyst
for sonochemical synthesis of spirooxindoles in
water†
Cite this: RSC Adv., 2021, 11, 15360
*
Mahla Dadaei and Hossein Naeimi
Core/shell nanoparticles have a wide range of applications in the science of chemistry and biomedicine. The
core–shell material can be different and modified by changing the ingredients or the ratio of core to the shell.
In this research, a CoFe2O4@SiO2-guanidine nanocomposite was prepared and identified as an efficient
catalyst for the one-pot synthesis of spirooxindole derivatives in water under ultrasonic irradiation
conditions. The advantages of this method are in its simplicity, saving costs and energy, high yields, short
reaction times, environmental friendliness, reusability and easy recovery of the catalyst using an external
magnet. The catalyst was characterized by XRD, SEM, TEM, EDX, FT-IR, TGA and VSM techniques.
Received 4th February 2021
Accepted 15th April 2021
DOI: 10.1039/d1ra00967b
rsc.li/rsc-advances
could be positive effect on increasing yields and rate of the reaction
due to the mechanical effect of shock waves. The main event in
1. Introduction
sonochemistry is the creation, growth and collapse of a bubble that
is formed in the liquid. The step leading to the growth of the bubble
occurs through the diffusion of solute vapor into the volume of the
bubble. The last stage is the crash of the bubble, which occurs when
the bubble size reaches its maximum value.
Core/shell nanoparticles have a wide range of applications in
the science of chemistry, biomedical, pharmaceutical, electronics
and catalysis. Therefore, these nanoparticles have attracted the
attention of researchers. The core–shell material can be different
and modied by changing the ingredients or the ratio of core to
the shell.17 Due to the coating of the shell material, the reactivity
of core decreases and the thermal stability changes. The purpose
of the core cover surface modication, reduce the consumption
of precious metals and increase the efficiency of functional
groups. In recent years, the applications of core–shell structured
MNPs in organic reactions have developed.18–24
Herein, we would like to report the synthesis and application
of guanidine immobilized on CoFe2O4@SiO2-CPTES nano-
composites as an environmentally benign, highly efficient and
reusable catalyst for the preparation of spirooxindole deriva-
tives via one-pot three component of isatin or 5-chloroisatin,
malononitrile or cyanoacetic esters and 1,3-dicarbonyl
compounds in water under ultrasonic irradiation.
Spirooxindole alkaloid compounds were rst extracted from
plants of the Apocynaceae and Rubiaceae families.1 Synthesis of
spiroxindole compounds among organic chemists is particularly
important because these heterocyclic compounds have a wide
range of pharmacological activities.2 These spirocycles possess
anticancer and antimicrobial activities.3 They are also known to
exhibit analgesic, anticonvulsant,4 and fungicidal5 activities.
Recently, few synthetic methods for the synthesis of spirox-
indoles have been reported in the literature. Some of the cata-
lysts that have been utilized in these methods are; PPh3,6
HAuCl4$3H2O,7 Incl3/SiO2,8 sodium stearate,9 and ethylenedi-
amine diacetate (EDDA).10
However, there are disadvantages to these reported methods,
such as; a poor yield, the use of toxic solvents, protracted
reaction time and reusability of the catalyst is hardship.
Although, each of the known methods for the synthesis of spi-
rooxindole compounds has its competency, however further
studies are still necessary for the efficient, environmental and
economical multicomponent methodology for the synthesis of
these heterocyclic compounds.
The use of ultrasonic waves in organic synthesis has been
boosted in recent years.11,12 This technique has many advantages
including saving costs and energy, nontoxic, environmentally
friendly solvent13,14 and reduce of side products.15 The power of
ultrasound radiation is (20 kHz to 10 MHz).16 Ultrasound irradiation
2. Experimental
2.1. General information
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
87317, I. R. Iran. E-mail: naeimi@kashanu.ac.ir; Fax: +98 3615912397; Tel: +98
3615912388
The chemicals were purchased from Fluka and Merck Chem-
ical Companies and used without purication. 1H NMR was
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d1ra00967b
recorded in DMSO-d6 solvent on
a Bruker DRX-400
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spectrometer with tetramethylsilane as internal reference. FT-
IR spectra were obtained as KBr pellets on a Perkin-Elmer 781
spectrophotometer and on an impact 400 Nicolet FT-IR spec-
trophotometer. The nanostructures were characterized using
a Holland Philips Xpert X-ray powder diffraction (XRD)
diffractometer (CuK, radiation, k 14 0.154056 nm), at a scanning
speed of 2ꢀ minꢁ1 from 100 to 100ꢀ (2Ø). The morphological
study of the nanocomposites was investigated by scanning
electron microscopy (SEM, SIGMA VP). The Electron Disper-
sive X-ray (EDX) analysis of the catalyst was performed on
Oxford Instrument Company. The nanocomposite was inves-
tigated by transmission electron microscopy (TEM, Zeiss-
EM10C-100 kV). Thermogravimetric analysis (TGA) was per-
formed on a mettler TA4000 system TG-50 at a heating rate of
10 K minꢁ1 under N2 atmosphere. The magnetic properties of
nanoparticles have been measured with a vibrating sample
magnetometer (VSM, PPMS-9T) at 300 K in Iran (Kashan
University). Melting points were obtained with a Yanagimoto
micro melting point apparatus and are uncorrected. The purity
determination of the substrates and reaction monitoring were
accomplished by TLC on silica-gel polygram SILG/UV 254
plates (from Merck Company).
2.2.4. Preparation of CoFe2O4@SiO2-guanidine. Finally,
according to the reported method in the literature with modi-
cations,26 the amount of 1 g of CoFe2O4@SiO2-CPTES was
dispersed in 10 mL of toluene in an ultrasonic bath for 10 min.
A mixture of functionalized MNPs was added to a suspension of
Na2CO3 (0.34 g) and guanidine (0.56 mL). The mixture was
reuxed for 30 h at 110 ꢀC. The CoFe2O4@SiO2-guanidine thus
obtained, washed with double distilled water until neutrality,
further washed with ethanol and dried at room temperature.
2.2.5. General procedure for the synthesis of spirooxindole
derivatives. A mixture of isatin (1 mmol, 0.147 g) or 5-chlor-
oisatin (1 mmol, 0.182 g), malononitrile (1 mmol, 0.07 g) or
cyanoacetic ester (1 mmol, 0.102 mL), 1,3-dicarbonyl
compounds in water and CoFe2O4@SiO2-guanidine (8 mg) was
added and reacted under ultrasonic irradiation (40 W). The
progress of the reaction was monitored by thin layer chroma-
tography (TLC) and was used ethyl acetate/petroleum ether (1/2)
as an eluent. Aer completion of the reaction, the catalyst was
separated by an external magnet. The organic residue was
washed with water for several times and dried under vacuum to
give the pure product. The products were conrmed by spectral
data and physical data.
2-Amino-20,5-dioxo-5H-spiro[indeno[1,2-b]pyran-4,30-indoline]-
3-carbonitrile. Yellow solid, mp 207–210 ꢀC. IR (KBr) n(cmꢁ1):
2.2. Catalyst preparation
1
3316, 3193, 2201, 1731, 1669, 1602, 1470, 1336, 1212. H NMR
2.2.1. General procedure for preparation of CoFe2O4
nanoparticles. Firstly, cobalt ferrite nanoparticles (CoFe2O4)
were synthesized by co-precipitation procedure, according to
the reported method in the literature.25 The 3 g solution of
sodium hydroxide was added drop wise to a mixture of CoCl2-
$6H2O (1.19 g) and FeCl3$6H2O (2.70 g). The pH of the solution
was constantly monitored as the NaOH solution was slowly
added. The reactants were stirred using a magnetic stirrer till
the pH of the solution was close to 13 for 1 h at reux temper-
ature. The black precipitate of CoFe2O4 were centrifuged and
washed several times with double distilled water and ethanol.
(400 MHz, DMSO-d6) d (ppm): 6.87 (d, 1H, Ar–H, J ¼ 8.0 Hz), 6.95
(t, 1H, Ar–H, J ¼ 8.0 Hz), 7.21 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.24 (s,
1H, Ar–H), 7.29 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.36 (d, 1H, Ar–H, J ¼
8.0 Hz), 7.43 (t, 1H, Ar–H, J ¼ 8.0 Hz), 7.56 (t, 1H, Ar–H, J ¼ 8.0
Hz), 7.70 (s, 2H, NH2), 10.68 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) d (ppm): 45.69, 57.08, 107.17, 109.71, 117.34, 118.78,
122.17, 122.23, 124.57, 129.12, 130.43, 131.30, 131.98, 133.64,
135.07, 141.77, 160.41, 167.47, 177.34, 189.34.
70-Amino-2,40-dioxo-20-thioxo-10,20,30,40-tetrahydrospiro [indo-
line-3,50-pyrano[2,3-d]pyrimidine]-60-carbonitrile. White solid, mp
232–235 ꢀC, lit. 27 (mp 240–241 ꢀC). IR (KBr) n(cmꢁ1): 3309, 3156,
1
ꢀ
The acquired substance was calcined for 4 h at 300 C.
2196, 1718, 1675, 1571, 1470, 1395, 1339, 1104. H NMR (400
2.2.2. General procedure for preparation of nano-CoFe2-
O4@SiO2 core–shell. The core–shell CoFe2O4@SiO2 nano-
particles were obtained according to the reported method in the
literature with minor modications.25 1 g of the CoFe2O4 NPs
was dispersed in 10 mL deionized water and 20 mL absolute
ethanol by sonication for 30 min. Then, 5 mL NH3 and 1 mL
tetraethylorthosilicate (TEOS) were added to the reaction
mixture and was stirred at 40 ꢀC for 24 h under the condition of
N2 atmosphere. Finally, the precipitates, CoFe2O4@SiO2 MNPs,
were washed with deionized water and ethanol for 3 times and
MHz, DMSO-d6) d (ppm): 6.77 (d, 1H, Ar–H, J ¼ 8.0 Hz), 6.89 (t,
1H, Ar–H, J ¼ 8.0 Hz), 7.13 (t, 1H, Ar–H, J ¼ 2.0 Hz), 7.15 (d, 1H,
Ar–H, J ¼ 8.0 Hz), 7.33 (s, 2H, NH2), 10.48 (s, 1H, NH), 12.15 (s,
1H, NH), 13.85 (s, 1H, NH).
70-Amino-2,20,40-trioxo-10,20,30,40-tetrahydrospiro[indoline-3,50-
pyrano[2,3-d]pyrimidine]-60-carbonitrile. White solid, mp 275–
277 ꢀC, lit. (mp 274–276 ꢀC). IR (KBr) n(cmꢁ1): 3353, 3304,
28
3145, 2829, 2203, 1723, 1673, 1395, 1616, 1531, 1468, 1337,
1111. 1H NMR (400 MHz, DMSO-d6) d (ppm): 6.77 (d, 1H, Ar–H, J
¼ 8.0 Hz), 6.89 (t, 1H, Ar–H, J ¼ 6.0 Hz), 7.12 (d, 1H, Ar–H, J ¼
8.0 Hz), 7.15 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.37 (s, 2H, NH2), 10.47 (s,
1H, NH), 11.12 (s, 1H, NH), 12.30 (s, 1H, NH).
70-Amino-5-chloro-2,40-dioxo-20-thioxo-10,20,30,40-tetrahydro
spiro[indoline-3,50-pyrano[2,3-d]pyrimidine]-60-carbonitrile. White
solid, mp 228–230 ꢀC, lit. 28 (mp 224–226 ꢀC). IR (KBr) n(cmꢁ1):
3358, 3278, 3150, 2849, 2196, 1679, 1570, 1476, 1340, 1172,
1110, 1066. 1H NMR (400 MHz, DMSO-d6) d (ppm): 6.79 (d, 1H,
Ar–H, J ¼ 8.0 Hz), 7.19–7.22 (dd, 1H, Ar–H, J ¼ 12.0 Hz, J ¼ 4.0
ꢀ
dried at 80 C for 10 h.
2.2.3. Preparation of CoFe2O4@SiO2-CPTES. The surface of
silica nanoparticles can be easily functionalized and were ob-
tained according to the reported method in the literature with
minor modications.26 To 2.5 mL of the 3-chloropropyl-
triethoxysilane (CPTES) was slowly added 1 g of CoFe2O4@-
SiO2 MNPs solution suspended in dry toluene. The solution was
reuxed for 24 h under an inert atmosphere, ltered and
washed subsequently with toluene, dichloromethane and dried
ꢀ
at 80 C for 10 h.
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Hz), 7.37 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.47 (s, 2H, NH2), 10.65 (s,
1H, NH), 12.43 (s, 1H, NH), 13.86 (s, 1H, NH).
70-Amino-5-chloro-2,20,40-trioxo-10,20,30,40-tetrahydrospiro
[indoline-3,50-pyrano[2,3-d]pyrimidine]-60-carbonitrile.
White
solid, mp 242–245 ꢀC, lit. 29 (mp 250–258 ꢀC). IR (KBr) n(cmꢁ1):
3296, 3163, 2821, 2200, 1693, 1644, 1537, 1401, 1336, 1121, 999.
1H NMR (400 MHz, DMSO-d6) d (ppm): 6.78 (d, 1H, Ar–H, J ¼ 8.0
Hz), 7.18–7.21 (dd, 1H, Ar–H, J ¼ 12.0 Hz, J ¼ 4.0 Hz), 7.31 (d,
1H, Ar–H, J ¼ 8.0 Hz), 7.43 (s, 2H, NH2), 10.60 (s, 1H, NH), 11.12
(s, 1H, NH), 12.32 (s, 1H, NH).
2-Amino-50-chloro-20,5-dioxo-5H-spiro[indeno[1,2-b]pyran-4,30-
indoline]-3-carbonitrile. Yellow solid, mp 219–222 ꢀC. IR (KBr)
n(cmꢁ1): 3316, 3241, 3199, 2196, 1738, 1667, 1600, 1472, 1334,
1
1209, 923. H NMR (400 MHz, DMSO-d6) d (ppm): 6.89 (d, 1H,
Ar–H, J ¼ 8 Hz), 7.26 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.30 (d, 1H, Ar–H,
J ¼ 8.0 Hz), 7.37 (d, 1H, Ar–H, J ¼ 8.0 Hz), 7.43 (d, 1H, Ar–H, J ¼
8.0 Hz), 7.45 (d, 1H, Ar–H, J ¼ 8.0 Hz), 7.56 (t, 1H, Ar–H, J ¼ 6.0
Hz), 7.78 (s, 2H, NH2), 10.83 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) d (ppm): 46.55, 56.96, 106.47, 112.36, 117.68, 118.87,
122.20, 124.98, 126.61, 129.06, 130.51, 131.33, 133.62, 134.37,
135.16, 140.70, 160.55, 167.83, 176.25, 189.35.
Fig. 1 XRD spectrum of (a) CoFe2O4, (b) CoFe2O4@SiO2-guanidine.
254 ꢀC, lit. (mp 256–258 ꢀC). IR (KBr) n(cmꢁ1): 3369, 3178,
30
1
2958, 1715, 1688, 1613, 1525, 1473, 1316, 1259. H NMR (400
MHz, DMSO-d6) d (ppm): 0.78 (t, 3H, CH3, J ¼ 6.0 Hz), 0.93 (s,
3H, CH3), 0.97 (s, 3H, CH3), 2.00 (d, 1H, CH, J ¼ 16.0 Hz), 2.14
(d, 1H, CH, J ¼ 16.0 Hz), 2.47 (d, 1H, CH, J ¼ 16.0 Hz), 2.57 (d,
1H, CH, J ¼ 16.0 Hz), 3.68–3.70 (m, 2H, CH2), 6.66 (d, 1H, Ar–H,
J ¼ 8.0 Hz), 6.75 (t, 1H, Ar–H, J ¼ 6.0 Hz), 6.82 (d, 1H, Ar–H, J ¼
8.0 Hz), 7.03 (t, 1H, Ar–H, J ¼ 8.0 Hz), 7.85 (s, 2H, NH2), 10.13 (s,
1H, NH).
Ethyl-2-amino-50-chloro-7,7-dimethyl-20,5-dioxo-5,6,7,8-tetrahy-
drospiro[chromene-4,30-indoline]-3-carboxylate. White solid, mp
278–281 ꢀC, lit. 30 (mp 275–278 ꢀC). IR (KBr) n(cmꢁ1): 3384, 3276,
1
2958, 1725, 1687, 1650, 1514, 1477, 1349, 1294, 1052. H NMR
(400 MHz, DMSO-d6) d (ppm): 0.81 (t, 3H, CH3, J ¼ 6.0 Hz), 0.95
(s, 3H, CH3), 0.99 (s, 3H, CH3), 2.04–2.15 (q, 2H, CH2, J ¼ 16.0
Hz), 2.50 (t, 2H, CH2, J ¼ 2.0 Hz), 3.67–3.70 (m, 2H, CH2), 6.67
(d, 1H, Ar–H, J ¼ 8.0 Hz), 6.89 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.07–
7.09 (dd, 1H, Ar–H, J ¼ 8.0 Hz, J ¼ 4 Hz), 7.93 (s, 2H, NH2), 10.31
(s, 1H, NH).
2-Amino-50-chloro-7,7-dimethyl-20,5-dioxo-5,6,7,8-tetrahydro
spiro[chromene-4,30-indoline]-3-carbonitrile. White solid, mp
292–294 C, lit. (mp > 300 C). IR (KBr) n(cmꢁ1): 3286, 3154,
ꢀ
30
ꢀ
1
2958, 2192, 1726, 1652, 1602, 1475, 1350, 1222, 1056. H NMR
(400 MHz, DMSO-d6) d (ppm): 1.01 (s, 6H, 2CH3), 2.14 (s, 2H,
CH2), 2.54 (d, 2H, CH2, J ¼ 12.0 Hz), 6.79 (d, 1H, Ar–H, J ¼ 8.0
Hz), 7.09 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.17–7.19 (dd, 1H, Ar–H, J ¼
8.0 Hz, J ¼ 4.0 Hz), 7.33 (s, 2H, NH2), 10.54 (s, 1H, NH).
30-Acetyl-60-amino-5-chloro-20-methyl-2-oxo-spiro[indoline-3,40-
pyran]-50-carbonitrile. White solid, mp 280–282 ꢀC. IR (KBr)
n(cmꢁ1): 3356, 3237, 2192, 1705, 1653, 1592, 1479, 1298, 1214,
1054. 1H NMR (400 MHz, DMSO-d6) d (ppm): 2.22 (s, 3H, CH3),
2.38 (s, 3H, CH3), 6.77 (d, 1H, Ar–H, J ¼ 8.0 Hz), 7.10 (d, 1H, Ar–
Ethyl-2-amino-7,7-dimethyl-20,5-dioxo-5,6,7,8-tetrahydrospiro
[chromene-4,30-indoline]-3-carboxylate. White solid, mp 252–
Scheme 1 Synthesis of the CoFe2O4@SiO2-guanidine catalyst.
15362 | RSC Adv., 2021, 11, 15360–15368
Fig. 2 SEM images of CoFe2O4@SiO2-guanidine.
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2-Amino-7,7-dimethyl-20,5-dioxo-5,6,7,8-tetrahydrospiro [chro-
mene-4,30-indoline]-3-carbonitrile. White solid, mp 288–290 ꢀC,
lit. 30 (mp 290–292 ꢀC). IR (KBr) n(cmꢁ1): 3375, 3312, 3142, 2960,
1
2192, 1722, 1655, 1604, 1469, 1349, 1220, 1054. H NMR (400
MHz, DMSO-d6) d (ppm): 0.99 (s, 3H, CH3), 1.02 (s, 3H, CH3),
2.06–2.18 (q, 2H, CH2, J ¼ 16 Hz), 2.54 (d, 2H, CH2, J ¼ 4.0 Hz),
6.77 (d, 1H, Ar–H, J ¼ 8.0 Hz), 6.88 (t, 1H, Ar–H, J ¼ 8.0 Hz), 6.97
(d, 1H, Ar–H, J ¼ 8.0 Hz), 7.13 (t, 1H, Ar–H, J ¼ 8.0 Hz), 7.23 (s,
2H, NH2), 10.39 (s, 1H, NH).
30-Acetyl-60-amino-20-methyl-2-oxo-spiro[indoline-3,40-pyran]-50-
carbonitrile. White solid, mp 240–243 ꢀC, lit. 31 (mp 243–245 ꢀC).
IR (KBr) n(cmꢁ1): 3378, 3346, 3120, 2188, 1709, 1680, 1653, 1467,
1296, 1211. 1H NMR (400 MHz, DMSO-d6) d (ppm): 2.13 (s, 3H,
CH3), 2.28 (s, 3H, CH3), 6.76 (d, 1H, Ar–H, J ¼ 8.0 Hz), 6.90 (t,
1H, Ar–H, J ¼ 8.0 Hz), 7.02 (d, 1H, Ar–H, J ¼ 8.0 Hz), 7.12 (s, 2H,
NH2), 7.15 (d, 1H, Ar–H, J ¼ 8.0 Hz), 10.38 (s, 1H, NH).
Fig. 3 The EDX pattern of the CoFe2O4@SiO2-guanidine.
3. Results and discussion
3.1. Preparation and characterization of catalyst
To prepare the catalyst, we have chosen a mixture of CoCl2-
$6H2O, FeCl3$6H2O and NaOH dissolved in deionized water
Fig. 4 The TEM image of the CoFe2O4@SiO2-guanidine.
H, J ¼ 4.0 Hz), 7.16 (d, 1H, Ar–H, J ¼ 4.0 Hz), 7.20 (s, 2H, NH2),
10.49 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) d (ppm): 19.80,
31.53, 56.13, 110.67, 114.41, 117.36, 123.19, 125.61, 128.15,
136.69, 140.88, 158.05, 159.01, 178.33, 197.03.
Fig. 6 TG analysis of CoFe2O4@SiO2-guanidine.
Fig. 5 FT-IR spectra of (a) CoFe2O4 nanoparticles, (b) CoFe2O4@SiO2, Fig. 7 Magnetization curves for (a) CoFe2O4 and (b) CoFe2O4@SiO2-
(c) CoFe2O4@SiO2-CPTES, (d) CoFe2O4@SiO2-guanidine.
guanidine.
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Scheme 2 The preparation of spirooxindole derivatives using nanocomposites as catalyst.
under reux condition according to the procedure reported in
The EDX pattern shown in Fig. 3 conrms the signals for
the literature.18 In the next step, the nanomagnetic was coated carbon, iron, cobalt, oxygen, nitrogen and silicon elements. The
with silica. Then, the resulting silica-coated CoFe2O4 nano- results of EDX, XRD and SEM for CoFe2O4@SiO2-guanidine
particles were allowed to react under vigorous stirring with an nanocomposite conrm that nanoparticles were exactly fabri-
appropriate concentration of 3-chloropropyltriethoxysilane.25,26 cated on the surface.
Finally, the reaction of CoFe2O4@SiO2 carried out with guani-
The TEM image of the nanocomposite was shown in Fig. 4.
dine in toluene under reux condition for 30 h to give amino- This image displays the formation of CoFe2O4@SiO2-guanidine
functionalized silica-coated nanomagnetic (CoFe2O4@SiO2- nanostructure that contains core–shell nature.
guanidine). The synthetic path for preparation of the catalyst is
Furthermore, the Fig. 5a–d shows the FT-IR spectra of
shown in Scheme 1. In order to characterize the catalyst struc- CoFe2O4 MNPs, CoFe2O4@SiO2, CoFe2O4@SiO2-CPTES and
ture, the synthesized nanocatalyst was analysed using XRD, CoFe2O4@SiO2-guanidine, respectively. The FT-IR spectrum of
SEM, EDX, TEM, FT-IR, TGA and VSM techniques.
CoFe2O4 MNPs shows peaks characteristic of Co–O at 603 cmꢁ1
The structure of the magnetic nanocatalyst was character- and the broad band at 3428 cmꢁ1 is due to the O–H of adsorbed
ized by XRD as shown in Fig. 1. There are six diffraction peaks at
2q about 30.26, 35.61, 43.24, 53.73, 57.16 and 62.72 corre-
sponding to the (220), (311), (400), (422), (511) and (440) planes Table 2 Optimization of ultrasonic power by using CoFe2O4@SiO2-
CPTES-guanidine in watera
in the CoFe2O4 which is correspond to the standard pattern. As
shown in Fig. 1, the positions of all peaks in the XRD pattern of
CoFe2O4@SiO2-guanidine were according to standard XRD
pattern of CoFe2O4.
The morphology of the CoFe2O4@SiO2-guanidine magnetic
nanocomposite was determined by SEM. The average size of
nanoparticles on the support determined from Fig. 2 was about
54 nm.
Entry
Power (W)
Time (min)
Yield (%)
1
2
3
4
30
35
40
45
10
10
10
10
70
84
90
90
a
Reaction condition: isatin (1 mmol), malononitrile (1 mmol),
dimedone (1 mmol) under ultrasonic irradiation and water as a solvent.
Table 1 Effect of different amounts of the catalyst on the reaction a
Table 3 Optimization of solvents in the presence of CoFe2O4@SiO2-
Amount of catalyst
(mg)
guanidine (8 mg) under ultrasonic irradiation (40 W)a
Entry
Time (min)
Yieldb (%)
Entry
Solvent
Time (min)
Yieldb (%)
1
2
3
4
5
6
No catalyst
10
10
10
10
10
10
—
20
40
65
70
70
2
4
6
8
9
1
2
3
4
5
EtOH
Water
DMF
Chloroform
Toluene
10
10
10
10
10
68
90
50
20
15
a
a
Reaction condition: isatin (1 mmol), malononitrile (1 mmol),
Reaction condition: isatin (1 mmol), malononitrile (1 mmol),
dimedone (1 mmol) under ultrasonic irradiation and water as dimedone (1 mmol) and CoFe2O4@SiO2-guanidine (8 mg) under
a solvent. b Isolated yield.
ultrasound irradiation (40 W), at sonicated time. b Isolated yields.
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Table 4 The preparation of spirooxindole derivatives using CoFe2O4@SiO2-guanidine as catalyst at green conditionsa
Entry
Isatin
Nitril
Carbonyl compound
Product
Time (min)
Yieldb (%)
1
1a
2a
3a
15
94
2
3
4
5
1a
1a
1b
1b
2a
2a
2a
2a
3b
3c
3b
3c
10
92
92
91
93
8
10
10
6
7
1b
1b
2a
2b
3a
3d
12
15
92
88
8
9
1a
1b
2b
2a
3d
3d
15
10
90
87
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Table 4 (Contd.)
Entry
10
Isatin
Nitril
Carbonyl compound
Product
Time (min)
Yieldb (%)
1b
1a
2a
3e
10
92
11
2a
2a
3d
3e
10
90
92
12
1a
8
a
Reaction condition: isatin/5-chloroisatin (1 mmol), malononitrile/cyanoacetic esters (1 mmol), 1,3-dicarbonyl compounds and CoFe2O4@SiO2-
guanidine (8 mg) under ultrasound irradiation (40 W), water as a solvent condition. b Isolated yields.
water molecule and silica surface (Fig. 5a). Fig. 1b shows the FT- temperature. As shown in Fig. 7, MNPs to 15 emu gꢁ1 in the
IR spectrum of CoFe2O4@SiO2 MNPs. The band at 1089 cmꢁ1 is nal CoFe2O4@SiO2-guanidine catalyst. These consequences
attributed to the vibration of Si–O–Si bonds (Fig. 5b). Fig. 5c show that the magnetization property reduces via coating and
shows the FT-IR spectrum of the CoFe2O4@SiO2-CPTES. The functionalization surface of the CoFe2O4 nanoparticles. But the
FT-IR spectrum shows two peaks at 2924 and 2854 cmꢁ1 which advantage of the nanocomposite is that can be easily separated
are related to C–H stretching vibrations. In comparison to by an external magnet from the mixture reaction aer the
CoFe2O4@SiO2-CPTES, the presence of new bands in CoFe2- catalytic reaction.
O4@SiO2-guanidine is observed and the guanidine is recog-
Finally, the prepared CoFe2O4@SiO2-guanidine was used as
nized by the presence of stretching vibrations of N–H bonds at heterogeneous catalyst in the reaction of isatin or 5-chlor-
3402 cmꢁ1. The stretching vibration of C]N bonds at oisatin, malononitrile or cyanoacetic ester and 1,3-dicarbonyl
1664 cmꢁ1 are indicated (Fig. 5d).
compounds in 1 : 1 : 1 mole ratio under ultrasonic irradiation
In Fig. 6, the TG analysis of CoFe2O4@SiO2-guanidine are and water as a solvent (Scheme 2).
displayed. The primary small weight loss about 5% below
To optimize the reaction conditions in amount of catalyst,
200 ꢀC which corresponds to the removal of physically adsorbed condensation of isatin (1 mmol), malononitrile (1 mmol),
solvent and surface hydroxyl groups. The weight loss observed dimedone (1 mmol) was selected as a model reaction and
about 15% between 200–800 ꢀC in TGA curve of CoFe2O4@SiO2- studied under different conditions.
guanidine is mainly related to the decomposition of supported
organic components on the nanoparticles (Fig. 6).
In order to obtain the optimal amount of the catalyst, the
reaction was carried out in the presence of different amounts of
Magnetic properties of CoFe2O4 nanoparticles, CoFe2O4@- catalyst under ultrasonic irradiation and water as a solvent
SiO2-guanidine were investigated by VSM technique at room (Table 1).
Table 5 Comparison of the present work with previously reported works for synthesis of spirooxindoles
Entry
Catalyst
Condition
Time (min)
Yield (%)
Ref.
1
2
3
4
5
6
Fe3O4@SiO2-imid-PMA
SBA-Pr-NH2
ZnS NP
MgO NP
CsxH3ꢁX PW12O40NP
CoFe2O4@SiO2-guanidine
Reux, H2O
Reux, H2O
U. S, H2O
Thermal, H2O
Thermal, CH3CN
U. S, H2O
90
5
11
120
90
10
93
91
95
95
88
90
32
33
34
35
36
This work
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Scheme 3 Proposed reaction mechanism for spirooxindole derivatives by CoFe2O4@SiO2-guanidine nanocomposite as a catalyst.
As can be seen in Table 1, the reaction was efficiently per-
In a plausible mechanism, at rst, malononitrile is activated
formed using 8 mg of the catalyst under ultrasonic irradiation by catalyst and attacks to the carbonyl group of isatin and
and water as a solvent and the desired product was obtained in removes of H2O. Then, in second step, 1,3-dicarbonyl
high yield within a short reaction time (Table 1, entry 5).
compounds is activated by catalyst and attacks to the a carbon
Aer the optimization of the catalyst amount, the reaction atom of isatin. Then a tautomer is performed and the hydroxyl
was carried out in water under ultrasonic irradiation at different group attack on the carbon of nitrile and the nal product is
powers (Table 2). In the same way, the highest yield of product produced (Scheme 3).
was resulted from the reaction run under ultrasonic irradiation
with a power of 40 W (Table 2, entry 3).
3.2. Catalyst reusability
In continuation, the reaction of isatin (1 mmol), malononi-
As shown in Fig. 8, it was investigated the reusability of
trile (1 mmol), dimedone (1 mmol) and CoFe2O4@SiO2-guani-
CoFe2O4@SiO2-guanidine as heterogeneous catalyst for the
dine (8 mg) as catalyst and power of 40 W was carried out in
reaction of isatin, malononitrile, indandion as a model reac-
various solvents (Table 3). The best results were obtained using
tion. Aer the completion of the reaction, the catalyst was
separated from the reaction mixture using an external magnet
water as a solvent (Table 3, entry 2).
Aer optimization of the catalyst amount, ultrasonic power
and the residual catalyst was washed with ethyl acetate and
and optimization of solvents, synthesis of spirooxindole deriv-
dried in an oven at 50 ꢀC. The recycled catalyst could be reused
atives were carried out. The corresponding results are depicted
for three times without considerable loss of its catalytic activity.
in Table 4.
The present work was compared with the previously reported
works for synthesis of spirooxindoles and the results are shown
in Table 5. It was found that the present work was the better
4. Conclusion
In summary, this paper proposed a new protocol for the
synthesis of spirooxindole derivatives in the presence of
CoFe2O4@SiO2-guanidine nanocomposites (core–shell) as
a nanocatalyst in water as a solvent under ultrasonic irradiation.
The main advantages of this present procedure are the easy
recovery of catalyst, non-toxic, small amount of used catalyst
and given products with high yields and short reaction times.
than the other works on the basis of reaction times, product
yields and used catalyst amounts for the reactions (Table 5,
entry 6 vs. entries 1–5).
Conflicts of interest
There are no conicts to declare.
Acknowledgements
The authors are grateful to University of Kashan for supporting
this work by Grant No. 159148/85.
Fig. 8 The reusability of the CoFe2O4@SiO2-guanidine catalyst.
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18 M. Shaker and D. Elhamifar, New J. Chem., 2020, 44, 3445–
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