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

Abstract

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.

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1. Introduction

Spirooxindole alkaloid compounds were first 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 spiroxindoles have been reported in the literature. Some of the catalysts that have been utilized in these methods are; PPh₃,⁶ HAuCl₄·3H₂O,⁷ Incl₃/SiO₂,⁸ sodium stearate,⁹ and ethylenediamine 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 spirooxindole 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 solvent^13,14 and reduce of side products.¹⁵ The power of ultrasound radiation is (20 kHz to 10 MHz).¹⁶ Ultrasound irradiation could be positive effect on increasing yields and rate of the reaction due to the mechanical effect of shock waves. The main event in 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 modified 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 modification, 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 nanocomposites as an environmentally benign, highly efficient and reusable catalyst for the preparation of spirooxindole derivatives via one-pot three component of isatin or 5-chloroisatin, malononitrile or cyanoacetic esters and 1,3-dicarbonyl compounds in water under ultrasonic irradiation.

2. Experimental

2.1. General information

The chemicals were purchased from Fluka and Merck Chemical Companies and used without purification. ¹H NMR was recorded in DMSO-d₆ solvent on a Bruker DRX-400 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 spectrophotometer. The nanostructures were characterized using a Holland Philips Xpert X-ray powder diffraction (XRD) diffractometer (CuK, radiation, k ¼ 0.154056 nm), at a scanning speed of 2° min⁻¹ from 100 to 100° (2Ø). The morphological study of the nanocomposites was investigated by scanning electron microscopy (SEM, SIGMA VP). The Electron Dispersive X-ray (EDX) analysis of the catalyst was performed on Oxford Instrument Company. The nanocomposite was investigated by transmission electron microscopy (TEM, Zeiss-EM10C-100 kV). Thermogravimetric analysis (TGA) was performed on a mettler TA4000 system TG-50 at a heating rate of 10 K min⁻¹ 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. Catalyst preparation

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 reflux temperature. The black precipitate of CoFe₂O₄ were centrifuged and washed several times with double distilled water and ethanol. The acquired substance was calcined for 4 h at 300 °C.

2.2.2. General procedure for preparation of nano-CoFe₂O₄@SiO₂ core–shell. The core–shell CoFe₂O₄@SiO₂ nanoparticles were obtained according to the reported method in the literature with minor modifications.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 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 obtained according to the reported method in the literature with minor modifications.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 refluxed for 24 h under an inert atmosphere, filtered and washed subsequently with toluene, dichloromethane and dried at 80 °C for 10 h.

2.2.4. Preparation of CoFe₂O₄@SiO₂-guanidine. Finally, according to the reported method in the literature with modifications,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 refluxed 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-chloroisatin (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 chromatography (TLC) and was used ethyl acetate/petroleum ether (1/2) as an eluent. After 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 confirmed by spectral data and physical data.
2-Amino-2′,5-dioxo-5H-spiro[indeno[1,2-b]pyran-4,3′-indoline]-3-carbonitrile. Yellow solid, mp 207–210 °C. IR (KBr) ν(cm⁻¹): 3316, 3193, 2201, 1731, 1669, 1602, 1470, 1336, 1212. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 6.87 (d, 1H, Ar–H, J = 8.0 Hz), 6.95 (t, 1H, Ar–H, J = 8.0 Hz), 7.21 (d, 1H, Ar–H, J = 4.0 Hz), 7.24 (s, 1H, Ar–H), 7.29 (d, 1H, Ar–H, J = 4.0 Hz), 7.36 (d, 1H, Ar–H, J = 8.0 Hz), 7.43 (t, 1H, Ar–H, J = 8.0 Hz), 7.56 (t, 1H, Ar–H, J = 8.0 Hz), 7.70 (s, 2H, NH₂), 10.68 (s, 1H, NH). ¹³C NMR (100 MHz, DMSO-d₆) δ (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.
7′-Amino-2,4′-dioxo-2′-thioxo-1′,2′,3′,4′-tetrahydrospiro [indoline-3,5′-pyrano[2,3-d]pyrimidine]-6′-carbonitrile. White solid, mp 232–235 °C, lit. ²⁷ (mp 240–241 °C). IR (KBr) ν(cm⁻¹): 3309, 3156, 2196, 1718, 1675, 1571, 1470, 1395, 1339, 1104. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 6.77 (d, 1H, Ar–H, J = 8.0 Hz), 6.89 (t, 1H, Ar–H, J = 8.0 Hz), 7.13 (t, 1H, Ar–H, J = 2.0 Hz), 7.15 (d, 1H, Ar–H, J = 8.0 Hz), 7.33 (s, 2H, NH₂), 10.48 (s, 1H, NH), 12.15 (s, 1H, NH), 13.85 (s, 1H, NH).
7′-Amino-2,2′,4′-trioxo-1′,2′,3′,4′-tetrahydrospiro[indoline-3,5′-pyrano[2,3-d]pyrimidine]-6′-carbonitrile. White solid, mp 275–277 °C, lit. ²⁸ (mp 274–276 °C). IR (KBr) ν(cm⁻¹): 3353, 3304, 3145, 2829, 2203, 1723, 1673, 1395, 1616, 1531, 1468, 1337, 1111. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 6.77 (d, 1H, Ar–H, J = 8.0 Hz), 6.89 (t, 1H, Ar–H, J = 6.0 Hz), 7.12 (d, 1H, Ar–H, J = 8.0 Hz), 7.15 (d, 1H, Ar–H, J = 4.0 Hz), 7.37 (s, 2H, NH₂), 10.47 (s, 1H, NH), 11.12 (s, 1H, NH), 12.30 (s, 1H, NH).
7′-Amino-5-chloro-2,4′-dioxo-2′-thioxo-1′,2′,3′,4′-tetrahydro spiro[indoline-3,5′-pyrano[2,3-d]pyrimidine]-6′-carbonitrile. White solid, mp 228–230 °C, lit. ²⁸ (mp 224–226 °C). IR (KBr) ν(cm⁻¹): 3358, 3278, 3150, 2849, 2196, 1679, 1570, 1476, 1340, 1172, 1110, 1066. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 6.79 (d, 1H, Ar–H, J = 8.0 Hz), 7.19–7.22 (dd, 1H, Ar–H, J = 12.0 Hz, J = 4.0 Hz), 7.37 (d, 1H, Ar–H, J = 4.0 Hz), 7.47 (s, 2H, NH₂), 10.65 (s, 1H, NH), 12.43 (s, 1H, NH), 13.86 (s, 1H, NH).
7′-Amino-5-chloro-2,2′,4′-trioxo-1′,2′,3′,4′-tetrahydrospiro [indoline-3,5′-pyrano[2,3-d]pyrimidine]-6′-carbonitrile. White solid, mp 242–245 °C, lit. ²⁹ (mp 250–258 °C). IR (KBr) ν(cm⁻¹): 3296, 3163, 2821, 2200, 1693, 1644, 1537, 1401, 1336, 1121, 999. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 6.78 (d, 1H, Ar–H, J = 8.0 Hz), 7.18–7.21 (dd, 1H, Ar–H, J = 12.0 Hz, J = 4.0 Hz), 7.31 (d, 1H, Ar–H, J = 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-5′-chloro-2′,5-dioxo-5H-spiro[indeno[1,2-b]pyran-4,3′-indoline]-3-carbonitrile. Yellow solid, mp 219–222 °C. IR (KBr) ν(cm⁻¹): 3316, 3241, 3199, 2196, 1738, 1667, 1600, 1472, 1334, 1209, 923. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 6.89 (d, 1H, Ar–H, J = 8 Hz), 7.26 (d, 1H, Ar–H, J = 4.0 Hz), 7.30 (d, 1H, Ar–H, J = 8.0 Hz), 7.37 (d, 1H, Ar–H, J = 8.0 Hz), 7.43 (d, 1H, Ar–H, J = 8.0 Hz), 7.45 (d, 1H, Ar–H, J = 8.0 Hz), 7.56 (t, 1H, Ar–H, J = 6.0 Hz), 7.78 (s, 2H, NH₂), 10.83 (s, 1H, NH). ¹³C NMR (100 MHz, DMSO-d₆) δ (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.
Ethyl-2-amino-5′-chloro-7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahydrospiro[chromene-4,3′-indoline]-3-carboxylate. White solid, mp 278–281 °C, lit. ³⁰ (mp 275–278 °C). IR (KBr) ν(cm⁻¹): 3384, 3276, 2958, 1725, 1687, 1650, 1514, 1477, 1349, 1294, 1052. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 0.81 (t, 3H, CH₃, J = 6.0 Hz), 0.95 (s, 3H, CH₃), 0.99 (s, 3H, CH₃), 2.04–2.15 (q, 2H, CH₂, J = 16.0 Hz), 2.50 (t, 2H, CH₂, J = 2.0 Hz), 3.67–3.70 (m, 2H, CH₂), 6.67 (d, 1H, Ar–H, J = 8.0 Hz), 6.89 (d, 1H, Ar–H, J = 4.0 Hz), 7.07–7.09 (dd, 1H, Ar–H, J = 8.0 Hz, J = 4 Hz), 7.93 (s, 2H, NH₂), 10.31 (s, 1H, NH).
Ethyl-2-amino-7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahydrospiro [chromene-4,3′-indoline]-3-carboxylate. White solid, mp 252–254 °C, lit. ³⁰ (mp 256–258 °C). IR (KBr) ν(cm⁻¹): 3369, 3178, 2958, 1715, 1688, 1613, 1525, 1473, 1316, 1259. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 0.78 (t, 3H, CH₃, J = 6.0 Hz), 0.93 (s, 3H, CH₃), 0.97 (s, 3H, CH₃), 2.00 (d, 1H, CH, J = 16.0 Hz), 2.14 (d, 1H, CH, J = 16.0 Hz), 2.47 (d, 1H, CH, J = 16.0 Hz), 2.57 (d, 1H, CH, J = 16.0 Hz), 3.68–3.70 (m, 2H, CH₂), 6.66 (d, 1H, Ar–H, J = 8.0 Hz), 6.75 (t, 1H, Ar–H, J = 6.0 Hz), 6.82 (d, 1H, Ar–H, J = 8.0 Hz), 7.03 (t, 1H, Ar–H, J = 8.0 Hz), 7.85 (s, 2H, NH₂), 10.13 (s, 1H, NH).
2-Amino-5′-chloro-7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahydro spiro[chromene-4,3′-indoline]-3-carbonitrile. White solid, mp 292–294 °C, lit. ³⁰ (mp > 300 °C). IR (KBr) ν(cm⁻¹): 3286, 3154, 2958, 2192, 1726, 1652, 1602, 1475, 1350, 1222, 1056. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 1.01 (s, 6H, 2CH₃), 2.14 (s, 2H, CH₂), 2.54 (d, 2H, CH₂, J = 12.0 Hz), 6.79 (d, 1H, Ar–H, J = 8.0 Hz), 7.09 (d, 1H, Ar–H, J = 4.0 Hz), 7.17–7.19 (dd, 1H, Ar–H, J = 8.0 Hz, J = 4.0 Hz), 7.33 (s, 2H, NH₂), 10.54 (s, 1H, NH).
3′-Acetyl-6′-amino-5-chloro-2′-methyl-2-oxo-spiro[indoline-3,4′-pyran]-5′-carbonitrile. White solid, mp 280–282 °C. IR (KBr) ν(cm⁻¹): 3356, 3237, 2192, 1705, 1653, 1592, 1479, 1298, 1214, 1054. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 2.22 (s, 3H, CH₃), 2.38 (s, 3H, CH₃), 6.77 (d, 1H, Ar–H, J = 8.0 Hz), 7.10 (d, 1H, Ar–H, J = 4.0 Hz), 7.16 (d, 1H, Ar–H, J = 4.0 Hz), 7.20 (s, 2H, NH₂), 10.49 (s, 1H, NH). ¹³C NMR (100 MHz, DMSO-d₆) δ (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.
2-Amino-7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahydrospiro [chromene-4,3′-indoline]-3-carbonitrile. White solid, mp 288–290 °C, lit. ³⁰ (mp 290–292 °C). IR (KBr) ν(cm⁻¹): 3375, 3312, 3142, 2960, 2192, 1722, 1655, 1604, 1469, 1349, 1220, 1054. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 0.99 (s, 3H, CH₃), 1.02 (s, 3H, CH₃), 2.06–2.18 (q, 2H, CH₂, J = 16 Hz), 2.54 (d, 2H, CH₂, J = 4.0 Hz), 6.77 (d, 1H, Ar–H, J = 8.0 Hz), 6.88 (t, 1H, Ar–H, J = 8.0 Hz), 6.97 (d, 1H, Ar–H, J = 8.0 Hz), 7.13 (t, 1H, Ar–H, J = 8.0 Hz), 7.23 (s, 2H, NH₂), 10.39 (s, 1H, NH).
3′-Acetyl-6′-amino-2′-methyl-2-oxo-spiro[indoline-3,4′-pyran]-5′-carbonitrile. White solid, mp 240–243 °C, lit. ³¹ (mp 243–245 °C). IR (KBr) ν(cm⁻¹): 3378, 3346, 3120, 2188, 1709, 1680, 1653, 1467, 1296, 1211. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 2.13 (s, 3H, CH₃), 2.28 (s, 3H, CH₃), 6.76 (d, 1H, Ar–H, J = 8.0 Hz), 6.90 (t, 1H, Ar–H, J = 8.0 Hz), 7.02 (d, 1H, Ar–H, J = 8.0 Hz), 7.12 (s, 2H, NH₂), 7.15 (d, 1H, Ar–H, J = 8.0 Hz), 10.38 (s, 1H, NH).

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 under reflux condition according to the procedure reported in the literature.¹⁸ In the next step, the nanomagnetic was coated with silica. Then, the resulting silica-coated CoFe₂O₄ nanoparticles were allowed to react under vigorous stirring with an appropriate concentration of 3-chloropropyltriethoxysilane.^25,26 Finally, the reaction of CoFe₂O₄@SiO₂ carried out with guanidine in toluene under reflux condition for 30 h to give amino-functionalized silica-coated nanomagnetic (CoFe₂O₄@SiO₂-guanidine). The synthetic path for preparation of the catalyst is shown in Scheme 1. In order to characterize the catalyst structure, the synthesized nanocatalyst was analysed using XRD, SEM, EDX, TEM, FT-IR, TGA and VSM techniques.

Scheme 1 Synthesis of the CoFe₂O₄@SiO₂-guanidine catalyst.

The structure of the magnetic nanocatalyst was characterized by XRD as shown in Fig. 1. There are six diffraction peaks at 2θ about 30.26, 35.61, 43.24, 53.73, 57.16 and 62.72 corresponding to the (220), (311), (400), (422), (511) and (440) planes 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.

Fig. 1 XRD spectrum of (a) CoFe₂O₄, (b) CoFe₂O₄@SiO₂-guanidine.

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.

Fig. 2 SEM images of CoFe₂O₄@SiO₂-guanidine.

The EDX pattern shown in Fig. 3 confirms the signals for carbon, iron, cobalt, oxygen, nitrogen and silicon elements. The results of EDX, XRD and SEM for CoFe₂O₄@SiO₂-guanidine nanocomposite confirm that nanoparticles were exactly fabricated on the surface.

Fig. 3 The EDX pattern of the CoFe₂O₄@SiO₂-guanidine.

The TEM image of the nanocomposite was shown in Fig. 4. This image displays the formation of CoFe₂O₄@SiO₂-guanidine nanostructure that contains core–shell nature.

Fig. 4 The TEM image of the CoFe₂O₄@SiO₂-guanidine.

Furthermore, the Fig. 5a–d shows the FT-IR spectra of CoFe₂O₄ MNPs, CoFe₂O₄@SiO₂, CoFe₂O₄@SiO₂-CPTES and CoFe₂O₄@SiO₂-guanidine, respectively. The FT-IR spectrum of CoFe₂O₄ MNPs shows peaks characteristic of Co–O at 603 cm⁻¹ and the broad band at 3428 cm⁻¹ is due to the O–H of adsorbed water molecule and silica surface (Fig. 5a). Fig. 1b shows the FT-IR spectrum of CoFe₂O₄@SiO₂ MNPs. The band at 1089 cm⁻¹ is attributed to the vibration of Si–O–Si bonds (Fig. 5b). Fig. 5c shows the FT-IR spectrum of the CoFe₂O₄@SiO₂-CPTES. The FT-IR spectrum shows two peaks at 2924 and 2854 cm⁻¹ which are related to C–H stretching vibrations. In comparison to CoFe₂O₄@SiO₂-CPTES, the presence of new bands in CoFe₂O₄@SiO₂-guanidine is observed and the guanidine is recognized by the presence of stretching vibrations of N–H bonds at 3402 cm⁻¹. The stretching vibration of C=N bonds at 1664 cm⁻¹ are indicated (Fig. 5d).

Fig. 5 FT-IR spectra of (a) CoFe₂O₄ nanoparticles, (b) CoFe₂O₄@SiO₂, (c) CoFe₂O₄@SiO₂-CPTES, (d) CoFe₂O₄@SiO₂-guanidine.

In Fig. 6, the TG analysis of CoFe₂O₄@SiO₂-guanidine are displayed. The primary small weight loss about 5% below 200 °C which corresponds to the removal of physically adsorbed solvent and surface hydroxyl groups. The weight loss observed about 15% between 200–800 °C in TGA curve of CoFe₂O₄@SiO₂-guanidine is mainly related to the decomposition of supported organic components on the nanoparticles (Fig. 6).

Fig. 6 TG analysis of CoFe₂O₄@SiO₂-guanidine.

Magnetic properties of CoFe₂O₄ nanoparticles, CoFe₂O₄@SiO₂-guanidine were investigated by VSM technique at room temperature. As shown in Fig. 7, MNPs to 15 emu g⁻¹ in the final CoFe₂O₄@SiO₂-guanidine catalyst. These consequences show that the magnetization property reduces via coating and functionalization surface of the CoFe₂O₄ nanoparticles. But the advantage of the nanocomposite is that can be easily separated by an external magnet from the mixture reaction after the catalytic reaction.

Fig. 7 Magnetization curves for (a) CoFe₂O₄ and (b) CoFe₂O₄@SiO₂-guanidine.

Finally, the prepared CoFe₂O₄@SiO₂-guanidine was used as heterogeneous catalyst in the reaction of isatin or 5-chloroisatin, malononitrile or cyanoacetic ester and 1,3-dicarbonyl compounds in 1 : 1 : 1 mole ratio under ultrasonic irradiation and water as a solvent (Scheme 2).

Scheme 2 The preparation of spirooxindole derivatives using nanocomposites as catalyst.

To optimize the reaction conditions in amount of catalyst, condensation of isatin (1 mmol), malononitrile (1 mmol), dimedone (1 mmol) was selected as a model reaction and studied under different conditions.

In order to obtain the optimal amount of the catalyst, the reaction was carried out in the presence of different amounts of catalyst under ultrasonic irradiation and water as a solvent (Table 1).

Table 1 Effect of different amounts of the catalyst on the reaction ^a

Entry	Amount of catalyst (mg)	Time (min)	Yield^b (%)
a Reaction condition: isatin (1 mmol), malononitrile (1 mmol), dimedone (1 mmol) under ultrasonic irradiation and water as a solvent.b Isolated yield.
1	No catalyst	10	—
2	2	10	20
3	4	10	40
4	6	10	65
5	8	10	70
6	9	10	70

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As can be seen in Table 1, the reaction was efficiently performed using 8 mg of the catalyst under ultrasonic irradiation and water as a solvent and the desired product was obtained in high yield within a short reaction time (Table 1, entry 5).

After the optimization of the catalyst amount, the reaction was carried out in water under ultrasonic irradiation at different powers (Table 2). In the same way, the highest yield of product was resulted from the reaction run under ultrasonic irradiation with a power of 40 W (Table 2, entry 3).

Table 2 Optimization of ultrasonic power by using CoFe₂O₄@SiO₂-CPTES-guanidine in water^a

Entry	Power (W)	Time (min)	Yield (%)
a Reaction condition: isatin (1 mmol), malononitrile (1 mmol), dimedone (1 mmol) under ultrasonic irradiation and water as a solvent.
1	30	10	70
2	35	10	84
3	40	10	90
4	45	10	90

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In continuation, the reaction of isatin (1 mmol), malononitrile (1 mmol), dimedone (1 mmol) and CoFe₂O₄@SiO₂-guanidine (8 mg) as catalyst and power of 40 W was carried out in various solvents (Table 3). The best results were obtained using water as a solvent (Table 3, entry 2).

Table 3 Optimization of solvents in the presence of CoFe₂O₄@SiO₂-guanidine (8 mg) under ultrasonic irradiation (40 W)^a

Entry	Solvent	Time (min)	Yield^b (%)
a Reaction condition: isatin (1 mmol), malononitrile (1 mmol), dimedone (1 mmol) and CoFe2O4@SiO2-guanidine (8 mg) under ultrasound irradiation (40 W), at sonicated time.b Isolated yields.
1	EtOH	10	68
2	Water	10	90
3	DMF	10	50
4	Chloroform	10	20
5	Toluene	10	15

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After optimization of the catalyst amount, ultrasonic power and optimization of solvents, synthesis of spirooxindole derivatives were carried out. The corresponding results are depicted in Table 4.

Table 4 The preparation of spirooxindole derivatives using CoFe₂O₄@SiO₂-guanidine as catalyst at green conditions^a

Entry	Isatin	Nitril	Carbonyl compound	Product	Time (min)	Yield^b (%)
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.
1	1a	2a	3a		15	94
2	1a	2a	3b		10	92
3	1a	2a	3c		8	92
4	1b	2a	3b		10	91
5	1b	2a	3c		10	93
6	1b	2a	3a		12	92
7	1b	2b	3d		15	88
8	1a	2b	3d		15	90
9	1b	2a	3d		10	87
10	1b	2a	3e		10	92
11	1a	2a	3d		10	90
12	1a	2a	3e		8	92

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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 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).

Table 5 Comparison of the present work with previously reported works for synthesis of spirooxindoles

Entry	Catalyst	Condition	Time (min)	Yield (%)	Ref.
1	Fe3O4@SiO2-imid-PMA	Reflux, H2O	90	93	32
2	SBA-Pr-NH2	Reflux, H2O	5	91	33
3	ZnS NP	U. S, H2O	11	95	34
4	MgO NP	Thermal, H2O	120	95	35
5	CsxH3−X PW12O40NP	Thermal, CH3CN	90	88	36
6	CoFe2O4@SiO2-guanidine	U. S, H2O	10	90	This work

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In a plausible mechanism, at first, malononitrile is activated by catalyst and attacks to the carbonyl group of isatin and removes of H₂O. Then, in second step, 1,3-dicarbonyl compounds is activated by catalyst and attacks to the α carbon atom of isatin. Then a tautomer is performed and the hydroxyl group attack on the carbon of nitrile and the final product is produced (Scheme 3).

Scheme 3 Proposed reaction mechanism for spirooxindole derivatives by CoFe₂O₄@SiO₂-guanidine nanocomposite as a catalyst.

3.2. Catalyst reusability

As shown in Fig. 8, it was investigated the reusability of CoFe₂O₄@SiO₂-guanidine as heterogeneous catalyst for the reaction of isatin, malononitrile, indandion as a model reaction. After the completion of the reaction, the catalyst was separated from the reaction mixture using an external magnet and the residual catalyst was washed with ethyl acetate and dried in an oven at 50 °C. The recycled catalyst could be reused for three times without considerable loss of its catalytic activity.

Fig. 8 The reusability of the CoFe₂O₄@SiO₂-guanidine catalyst.

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.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The authors are grateful to University of Kashan for supporting this work by Grant No. 159148/85.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra00967b

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