The preparation, characterization and application of COOH grafting on ferrite–silica nanoparticles

Abstract

Magnetic materials grafted with carboxylic acid (Fe₃O₄@SiO₂@COOH MNPs) were successfully prepared via the incorporation of maleic anhydride as a functional group on the surface of ferrite–silica nanoparticles. The properties of the magnetite nanoparticles prepared were characterized using transmission electron microscopy (TEM), FT-infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM), and X-ray diffraction (XRD) analysis. The prepared magnetic catalyst (Fe₃O₄@SiO₂@COOH) showed a high catalytic activity for the synthesis of diindolyl oxindoles via the coupling of indole and isatin compounds. The products were produced with good to high yield in an aqueous medium. The catalyst could be readily separated from the reaction mixture using a permanent magnet and showed high stability in recycling experiments.

---

1. Introduction

In an attempt to develop more sensitive, simple and cost effective materials, nanotechnology has attracted much attention. Magnetic nanoparticles, in particular, may contribute to such applications due to their distinct advantages such as their high surface area-to-volume ratio and therefore higher extraction capacity compared to micrometer-sized particles. The most important benefits are their facile and convenient separation upon applying an external magnetic field, which enables easy recovery and recycling of the scavenger, potentially even in the open environment.^1–5 Functionalized magnetic nanoparticles (MNPs) have emerged as viable alternatives to conventional materials, not just for heterogeneous catalysis,⁶ but also for homogenous catalysis.⁷ According to these attractive properties, many MNP supported catalysts have been designed and widely applied as novel magnetically separated catalysts in traditional metal catalysis,^8–10 organocatalysis,¹¹ and even enzymatic catalysis.¹² Recently, nanocrystalline ferrites (Fe₃O₄) have been identified as an ideal and most widely used support in catalysis^13,14 because of its low cost and easy preparation. Magnetite (Fe₃O₄) is inert and possesses a very active surface for immobilization or adsorption of catalytic fragments, including metal catalysts (Au, Pd, Pt, Cu, Ni, Co, and Ir), organocatalysts, and enzymes resulting in formation of remarkably sustainable catalysts. Magnetite has been used in recent years as a versatile catalyst support in a wide range of reactions, including Suzuki, Heck, Sonogashira, Hiyama, hydrogenation, reduction, oxidation, cycloaddition reactions, and asymmetric synthesis.^15–17

On a different note, oxindoles occupy an important place in the area of heterocyclic chemistry because they are frequently found in numerous natural and synthetic products along with useful biological activities. Oxindole derivatives often appear as important structural components in biologically active and natural compounds, which include antibacterial, antiprotozoal, and anti-inflammatory compounds, and progesterone receptors (PR) agonists.^18–20

In this study, we report on the preparation and use of carboxylic acid supported on ferrite–silica superparamagnetic nanoparticles. We introduce Fe₃O₄@SiO₂@COOH as a new, efficient, active, inexpensive and recyclable acidic magnetic nanocatalyst, which can be used for different organic functional group transformations in green processes. Then, we studied its catalytic activity in the synthesis of diindolyl oxindoles prepared by the coupling of indole and isatin derivatives. The oxindole derivatives were produced in good to high yield in an aqueous medium under mild conditions (Scheme 1).

Scheme 1

2. Results and discussion

Due to the reasonable need for the clean and green recovery of the acidic nanocatalyst, we synthesized carboxylic acid supported on Fe₃O₄@SiO₂ nanoparticles (Fe₃O₄@SiO₂@COOH) as a nanomagnetic system. This nanocatalyst was prepared in three steps: (i) the preparation of colloidal iron oxide magnetite nanoparticles (Fe₃O₄MNPs); the Fe₃O₄ MNPs were prepared via the reaction of FeCl₂·4H₂O and FeCl₃·6H₂O with sodium hydroxide in deionized water, (ii) coating silica on the Fe₃O₄ MNPs; to a mixture of Fe₃O₄ and tetraethoxysilane (TEOS) was added NH₃, which was stirred mechanically at room temperature to produce the Fe₃O₄@SiO₂ MNPs and (iii) the incorporation of carboxylic acid as a functional group on the surface of the ferrite–silica nanoparticles (Fe₃O₄@SiO₂@COOH); the Fe₃O₄@SiO₂ MNPs were treated with maleic anhydride in chloroform for 5 h to obtain the Fe₃O₄@SiO₂@COOH MNPs (Scheme 2).

Scheme 2 Preparation of the Fe₃O₄@SiO₂@COOH MNPs.

2.1 Characterization of the Fe₃O₄@SiO₂@COOH MNPs

The synthesized catalyst was characterized using different methods, including TEM, FT-IR, VSM, and XRD analyses.

2.1.1 XRD studies. The powder X-ray pattern recorded for the samples of Fe₃O₄, Fe₃O₄@SiO₂ and Fe₃O₄@SiO₂@COOH MNPs are shown in Fig. 1. The XRD patterns of the synthesized Fe₃O₄ nanoparticles display several relatively strong reflection peaks in region of 20–80°, which are quite similar to those of Fe₃O₄ nanoparticles reported by other groups. The patterns indicate a crystallized structure at 2θ = 30.2°, 35.3°, 43.2°, 53.5°, 57° and 62.5°, which were assigned to the (220), (311), (400), (422), (511) and (440) crystallographic faces of magnetite and is consistent with the standard pattern (JCPDS card no. 19-629). Extra reflections are not detected in the X-ray diffraction pattern. The XRD pattern of the Fe₃O₄@SiO₂ prepared shows an obvious diffusion peak at 13–28° that appeared because of the existence of amorphous silica. The calculated average crystallite size of Fe₃O₄@SiO₂@COOH MNPs, was 12.5–15 nm. Using Scherrer's equation D = 0.9λ/β cos θ, where D is the crystallite size, k is a correction factor = 0.9 used to account for particle shapes, β is the full width at half maximum (FWHM) of the peaks of all planes in the XRD pattern, λ is the wavelength of Cu target = 1.5406 Å, and θ is the Bragg angle.

Fig. 1 XRD pattern of (A) Fe₃O₄ MNPs (B) Fe₃O₄@SiO₂ MNPs (C) Fe₃O₄@SiO₂ @COOH MNPs.

2.1.2 VSM studies. Using a VSM at room temperature (300 K), the hysteretic curve of the Fe₃O₄@SiO₂@COOH nanoparticles was investigated. Plots of magnetization versus magnetic field for the Fe₃O₄@SiO₂@COOH nanoparticles are illustrated in Fig. 2. The carboxylated ferrite–silica nanoparticles exhibit superparamagnetic behaviour with a saturation magnetisation (M_s) of 36.3 emu g⁻¹ and without a magnetic hysteresis area, coercivity (H_c) and remanent magnetisation (M_r).

Fig. 2 The VSM pattern of the Fe₃O₄@SiO₂@COOH MNPs.

2.1.3 FT-IR studies. The successful conjugation of carboxylic acid onto the surface of the ferrite–silica sample was further supported by FT-IR spectroscopy, as shown in Fig. 3. The band located at 3420 cm⁻¹ can be attributed to the symmetric vibration of –OH groups. The bands at 1120 cm⁻¹ and 690 cm⁻¹ are corresponding to the Si–O and Fe–O groups. The peak at 2390 was ascribed to H–O–H bending vibrations of free or absorbed water.

Fig. 3 (a) The FT-IR spectrum of the Fe₃O₄ MNPs. (b) The FT-IR spectrum of the Fe₃O₄@SiO₂ MNPs. (c) The FT-IR spectrum of the Fe₃O₄@SiO₂@COOH MNPs.

2.1.4 EDX studies. Fig. 4 shows the energy-dispersive X-ray (EDX) spectrum of the Fe₃O₄@SiO₂@COOH MNPs. It was recorded to investigate the elemental composition of the Fe₃O₄@SiO₂@COOH MNPs. The results demonstrate that Si, Fe, C and O appear in the sample of Fe₃O₄@SiO₂@COOH MNPs. It can be noted that no impurities are present in the products. The ratio of Fe : Si determined from the EDX analysis was 1 : 0.7.

Fig. 4 EDX pattern of Fe₃O₄@SiO₂@COOH MNPs.

2.1.5 TEM studies. The TEM images of Fe₃O₄, Fe₃O₄@SiO₂ and the Fe₃O₄@SiO₂@COOH MNPs are shown in Fig. 5. The results showed the average product size of the Fe₃O₄@SiO₂@COOH MNPs was 14–18 nm, which was similar to the results obtained from the XRD analysis.

Fig. 5 The TEM images of: (a) Fe₃O₄ MNPs, (b) Fe₃O₄@SiO₂ MNPs and (c) Fe₃O₄@SiO₂@COOH MNPs.

2.2 Application of the Fe₃O₄@SiO₂@COOH MNPs

To show the merit of the synthesized nanocatalyst in organic reactions, the Fe₃O₄@SiO₂@COOH MNPs were used in the synthesis of oxindoles. To optimize the reaction conditions under conventional thermal conditions, the condensation of indole (2 mmol) with isatin (1 mmol) was initially selected as the model reaction to provide the desired diindolyl oxindole. The model reaction was examined in common organic solvents at 80 °C (Fig. 6). The reaction proceeded perfectly in polar solvents (EtOH, MeOH, and water), but the yields decreased when the reaction was carried out in low polar solvents (CHCl₃ and CH₂Cl₂). Water was used as a green solvent and produced diindolyl oxindole in excellent yield (80%).

Fig. 6 The effect of the solvent on the synthesis of diindolyl oxindole using the Fe₃O₄@SiO₂@COOH MNPs.

The reaction could be carried out under solvent-free conditions and gave a low yield (50%).

In another study, this reaction was tested in the presence of different ratios of the Fe₃O₄@SiO₂@COOH MNPs at 80 °C in an aqueous medium. As it is shown in Fig. 7, 0.003 g of the catalyst was sufficient to promote the reaction efficiently at 80 °C. Upon increasing the catalyst concentration the product yield increased significantly. Decreasing the catalyst concentration resulted in lower yields under the same conditions.

Fig. 7 The effect of the amount of nanocatalyst on the synthesis of diindolyl oxindole.

The effect of temperature was studied by carrying out the model reaction at different temperatures in water (room temperature, 60 °C, 80 °C and 100 °C) and the best result was obtained at 80 °C (Fig. 8).

Fig. 8 The effect of temperature on the synthesis of diindolyl oxindole.

To study the catalytic activity of the Fe₃O₄@SiO₂@COOH, the coupling of indole and isatin was carried out in water in the presence of 0.003 g of different nanometal oxides (Fig. 9). As it is evident from the results, Fe₃O₄@SiO₂@COOH was the most effective catalyst in terms of the yield of the oxindole (80%), whereas the other catalysts formed the product in yields of 20–42%.

Fig. 9 The effect of various nanocatalysts on the synthesis of diindolyl oxindole.

To establish the catalytic role of Fe₃O₄@SiO₂@COOH, indole was treated with isatin in the absence of a catalyst. In this case, the reaction proceeded in low yield (17%) over the model reaction time. Consequently, this reaction was carried out as a pseudo three-component reaction with twice amount of indole under heating conditions (80 °C) and diindolyl oxindole was achieved in an excellent yield (80%) with 2.0 equivalents of indole and 1.0 equivalent of isatin using 0.003 g of catalyst within 30 min in an aqueous medium.

After optimization of the reaction conditions, the efficiency and generality of the method were evaluated by the reaction of indole with a variety of isatin compounds. The results are summarized in Table 1. As it can be observed in Table 1, all the reactions were performed successfully to furnish the corresponding oxindoles in high to excellent yield and in relatively short reaction times. We were delighted that some more reactive carbon electrophiles such as 5-bromo isatin could serve as a good substrate in this reaction (Table 1, entries 1 and 5).

Table 1 The preparation of 3,3-diindolyl oxindole derivatives using Fe₃O₄@SiO₂@COOH^a

Entry	Reagents		Product	Time (min)	Yield^b (%)
	Indole	Isatin
a Reaction conditions: isatin compound (1 mmol), indole (2 mmol), Fe3O4@SiO2@COOH MNPs (0.003 g) and water (2 mL) at 80 °C.b The yield refers to pure isolated product.
1				30	98
2				30	85
3				60	78
4				30	80
5				30	80
6				60	60
7				60	65
8				30	80

---

At the end of the reaction, the catalyst could be recovered using an external magnetic field. The recycled catalyst was washed with dichloromethane and subjected to a second reaction process. The results show that the yield of product after four runs was only slightly reduced (Fig. 10).

Fig. 10 The recyclability of the Fe₃O₄@SiO₂@COOH in the synthesis of diindolyl oxindole.

3. Experimental

3.1 Chemicals

All starting materials and solvents were obtained from Merck (Germany) and Fluka (Switzerland), and were used without further purification. Purity determinations of the products were accomplished by TLC on silica-gel polygram SILG/UV 254 plates. Melting points were measured on an Electro thermal 9100 apparatus. IR spectra were obtained on a Perkin Elmer 781 spectrometer as KBr pellets and reported in cm⁻¹. ¹H NMR and ¹³C NMR spectra were measured on a Bruker DPX-250 Avance instrument at 250 MHz and 62.9 MHz, respectively, in CDCl₃ or DMSO-d₆ with the chemical shift reported in ppm relative to TMS as an internal standard. The morphology of the products was determined using transmission electron microscopy (TEM) on a CMPhilips10 model transmission electron microscope at an accelerating voltage of 100 kV. Power X-ray diffraction (XRD) was performed on a Bruker D₈-advance X-ray diffractometer with Cu K_α (λ = 0.154 nm) radiation. The magnetic properties were determined using a vibrating sample magnetometer (VSM) lakeshore 7200 at 300 K VSM lakeshore.

3.2 Catalyst preparation

3.2.1 Preparation of the Fe₃O₄ nanoparticles. First, 15 g of sodium hydroxide (NaOH) was dissolved into 25 mL of deionized water. Then, a mixture of 2 g of FeCl₂·4H₂O, 5.2 g of FeCl₃·6H₂O, 25 mL of deionized water and 0.85 mL of HCl was added dropwise with vigorous stirring to make a black solid product. The resultant mixture was heated using a water bath for 4 h at 80 °C. The black magnetite solid MNPs were isolated using an external magnet and washed three times with deionized water and ethanol, and then dried at 80 °C for 10 h.

3.2.2 Preparation of the Fe₃O₄@SiO₂ core–shells. Fe₃O₄ (0.50 g, 2.1 mmol) was dispersed in a mixture of ethanol (100 mL) and deionized water (20 mL) for 10 min. Then, 2.5 mL of NH₃ was added followed by the dropwise addition of tetraethoxysilane (TEOS) (1.5 mL). This solution was stirred mechanically for 6 h at room temperature. Then, the product Fe₃O₄@SiO₂ was separated using an external magnet and was washed three times with deionized water and ethanol, and then dried at 80 °C for 10 h.

3.2.3 Preparation of carboxylic acid supported on Fe₃O₄@SiO₂ nanoparticles [Fe₃O₄@SiO₂@COOH]. A mixture of Fe₃O₄@SiO₂ (0.2 g) and maleic anhydride (0.2 g) in CHCl₃ (10 mL) was magnetically stirred at 50 °C for 5 h. The Fe₃O₄@SiO₂@COOH MNPs were isolated using an external magnet, washed with ethanol and dichloromethane (50 mL) and then dried at 80 °C to obtain the Fe₃O₄@SiO₂@COOH.

3.3 Catalytic activity

3.3.1 General procedure for the preparation of diindolyl oxindole derivatives. The reactions were carried out by mixing indole (2 mmol) and the isatin compounds (1 mmol) in the presence of Fe₃O₄@SiO₂@COOH MNPs (0.003 g) in an aqueous medium with stirring at 80 °C using an oil bath. Thin layer chromatography clearly indicated the formation of the corresponding oxindoles. After completion of the reaction, the mixture was dissolved in acetone and the Fe₃O₄@SiO₂@COOH MNPs separated using an external magnet. Then, the solvent was removed under reduced pressure to produce the crude oxindole product. The product was purified via recrystallization using methanol as the solvent to afford the pure oxindole product.

4. Conclusion

Carboxylic acid supported on ferrite–silica nanoparticles (Fe₃O₄@SiO₂@COOH) as a nanocatalyst with a large density of acidic groups were synthesized using chemical methods. The present study provided a nanocatalyst with potential synthetic applications. In the present study, we have shown the unique advantages of the Fe₃O₄@SiO₂@COOH, which include high magnetic properties, a high density of acid functional groups on the nanocomposite surface, facile synthesis and easy separation using a permanent magnet. The Fe₃O₄@SiO₂@COOH MNPs are efficient and reusable nanocatalyst that can be used for the synthesis of diindolyl oxindole derivatives. The products were obtained using a one-pot coupling reaction of isatin compounds and indole in a short period of time. In addition, it is easy to separate and recover the catalyst for catalytic recycling.

Acknowledgements

We gratefully acknowledge from the Payame Noor University of Birjand for the financial support of this study.

References

1. A. Farrukh, A. Akram, A. Ghaffar, S. Hanif, A. Hamid, H. Duran and B. Yameen, ACS Appl. Mater. Interfaces, 2013, 5, 3784.
2. H. Parham, B. Zargar and R. Shiralipour, J. Hazard. Mater., 2012, 206, 94.
3. M. H. Baki and F. Shemirani, Anal. Methods, 2013, 5, 3255.
4. J. Zhao, B. Zhu, H. Yu, L. Yan, Q. Wei and B. Du, J. Colloid Interface Sci., 2013, 389, 46.
5. Y. Zhai, S. Duan, Q. He, X. Yang and Q. Han, Microchim. Acta, 2010, 169, 353.
6. (a) V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara and J. M. Basset, Chem. Rev., 2011, 111, 3036; (b) V. Polshettiwar and R. S. Varma, Green Chem., 2010, 12, 743.
7. (a) X. Gao, K. M. K. Yu, K. Y. Tam and S. C. Tsang, Chem. Commun., 2003, 2998; (b) V. Polshettiwar and R. S. Varma, Chem.–Eur. J., 2009, 15, 1582; (c) H. M. R. Gardimalla, D. Mandal, P. D. Stevens, M. Yen and Y. Gao, Chem. Commun., 2005, 4432; (d) P. D. Stevens, G. F. Li, J. D. Fan, M. Yen and Y. Gao, Chem. Commun., 2005, 4435.
8. (a) R. Abu-Reziq, H. Alper, D. S. Wang and M. L. Post, J. Am. Chem. Soc., 2006, 128, 5279; (b) G. Chouhan, D. S. Wang and H. Alper, Chem. Commun., 2007, 4809; (c) T. Hara, T. Kaneta, K. Mori, T. Mitsudome, T. Mizugaki, K. Ebitani and K. Kaneda, Green Chem., 2007, 9, 1246; (d) M. J. Jin and D. H. Lee, Angew. Chem., Int. Ed., 2010, 49, 1119.
9. (a) Y. H. Liu, J. Deng, J. W. Gao and Z. H. Zhang, Adv. Synth. Catal., 2012, 354, 441; (b) R. B. N. Baig and R. S. Varma, Green Chem., 2013, 15, 398.
10. J. Deng, L. P. Mo, F. Y. Zhao, L. L. Hou, L. Yang and Z. H. Zhang, Green Chem., 2011, 13, 2576.
11. (a) C. Ó. Dálaigh, S. A. Corr, Y. Gun'ko and S. J. Connon, Angew. Chem., Int. Ed., 2007, 46, 4329; (b) Y. Zhang and C. G. Xia, Appl. Catal., A, 2009, 366, 141; (c) X. X. Zheng, S. Z. Luo, L. Zhang and J. P. Cheng, Green Chem., 2009, 11, 455.
12. J. Lee, Y. Lee, J. K. Youn, H. B. Na, T. Yu, H. Kim, S. M. Lee, Y. M. Koo, J. H. Kwak, H. G. Park, H. N. Chang, M. Hwang, J. G. Park, J. Kim and T. Hyeon, Small, 2008, 4, 143.
13. M. B. Gawande, P. S. Brancoa and R. S. Varma, Chem. Soc. Rev., 2013, 42, 3371.
14. S. Roy and M. A. Pericas, Org. Biomol. Chem., 2009, 7, 2669.
15. B. Sreedhar, A. S. Kumar and P. S. Reddy, Tetrahedron Lett., 2010, 51, 1891.
16. V. Polshettiwar and R. S. Varma, Chem.–Eur. J., 2009, 15, 1582.
17. H. Pajouhesh, R. Parsons and F. D. Popp, J. Pharm. Sci., 1983, 72, 318.
18. F. Garrido, J. Ibanez, E. Gonalons and A. Giraldez, Eur. J. Med. Chem., 1975, 10, 143.
19. Y. Kamano, H. P. Zhang, Y. Ichihara, H. Kizu, K. Komiyama, H. Itokawa and G. R. Pettit, Tetrahedron Lett., 1995, 36, 2783.
20. C. Fischer, C. Meyers and E. M. Carreira, Helv. Chim. Acta, 2000, 83, 1175.

---