Highly efficient and recyclable novel spindles Fe2O3@SiO2/In2O3 nanomagnetic catalyst designed for green synthesis of azomethine compounds

A novel and reusable nanomagnetic catalyst, Fe2O3@SiO2/In2O3, was synthesized by a facile chemical approach in three successive steps. The nanocatalyst was characterized by FT-IR, XRD, SEM, EDX, TEM, and VSM. The XRD pattern displays the characteristic peaks of Fe2O3 and SiO2, accompanied by new peaks assigned to different planes of In2O3 that confirm the formation of In2O3 on the surface of Fe2O3@SiO2 core/shell spindles. The TEM micrographs show spindle-like particles of Fe2O3 covered with SiO2 shell, and the In2O3 nanoparticles in an average diameter of 20 nm are hung on the surface of the Fe2O3@SiO2. The nanomagnetic catalyst Fe2O3@SiO2/In2O3 was used for the transformation of the (4-nitrophenyl)-1-phenyl-1H-pyrazole-5-amine, and chalcones derivatives, into valuable azomethine compounds of 3-(substituted)-1-(pyridine-2-yl)allylidene)-3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-5-amine with high rate and efficient catalyst recovery. The yield obtained through the catalytic route reached 90–95% in shorter reaction times compared with uncatalyzed reaction method.


Introduction
The development of low-cost and recyclable catalysts is attractive to whom are involved in the green synthesis of organic compounds. By using catalysts, one can reduce the reaction temperature, and the amount of reagent-based waste, but enhance the selectivity of the reaction and avoid undesired side products, to quire a green technology [1]. Nanomaterials are used as catalysts in organic transformations to improve the selectivity and yield of various organic reactions and verify the aspects of green organic synthesis. This is due to their unique surface features, which are the essential difference from those of corresponding bulk materials [2,3]. In nanocatalysts, the high surface area/volume ratio implies a large number of active sites that participate in the reactions. Nanocomposites open a wide spectrum of desirable synergistic and complementary effects as heterogeneous catalysts for various organic transformations. Metal oxides based nanocomposites are used in heterogeneous catalysis of different organic transformations, due to their optimum porous size, extensive surface area, and large thermal stability [4,5]. The nano-mixed oxides attracted attention because they are more efficient than their single and bulk counterparts [6]. Recently, magnetic nanoparticles have also received considerable attention owing to their superparamagnetic properties, high adsorption capacities, and high surface area. Iron oxide nanoparticles (NPs) especially hematite (Fe 2 O 3 ) are used in

Instrumentation
The crystalline structure of synthesized nanoparticles was examined by X-ray powder diffraction (XRD) with a GNR APD 2000 PRO diffractometer. The X-ray beam was nickel-filtered Cu K α (λ = 1.5405 Å) radiation operating at 40 kV and 30 mA and the scanning speed was 0.03 degree/1 s. The morphology of the nanocomposites was obtained by a scanning electron microscope (SEM), (JEOL Japan JSM IT-100) and transmission electron microscope (200 kV TEM / FEG TEM, Japan, (JEM-2100), JEOL). The energy dispersive X-ray spectroscopy (EDX) IT100LA operating at an accelerating voltage of 20.00 keV is attached to the scanning electron microscope. Magnetic properties were measured by a vibrating sample magnetometer (VSM, Lake Shore, 7410 model) at room temperature. The FT-IR spectra were recorded by FT-IR-4100 (JASCO, Japan) spectrophotometer using KBr pellets in the wavenumber range 4000-400 cm −1 with a resolution of 2 cm −1 . The nuclear magnetic resonance ( 1 HNMR) spectra were recorded on a Bruker AC spectrometer (400 MHz) at 25 °C in d 6 -DMSO with TMS as an internal standard, and chemical shifts are reported in parts per million as d values; ( 13 CNMR) was set at 101 MHz. Mass spectra were measured on a Finnigan MAT 8222 EX electron impact mass spectrometer (EIMS) at 70 eV. The melting points were measured without corrections on a Gallenkamp melting point apparatus. Elemental analyses for C, H, and N were also carried out at the regional center for mycology and biotechnology, and the values were found to be within ± 0.4% of the theoretical ones unless otherwise indicated.

Synthesis of Fe 2 O 3 spindles
Fe 2 O 3 spindles were synthesized from an aqueous solution. 2 g of FeCl 3 .6H 2 O and 1 g of PVP were dissolved with stirring in 30 mL of water until a clear solution was developed. 2 g of anhydrous sodium acetate followed by 7 mL of ethylenediamine were added. The mixture was then sealed in an autoclave and heated at 200 °C for 10 h. The Fe 2 O 3 spindles were collected, washed perfectly with water, and dried [25] Fig. 1.

Synthesis of Fe 2 O 3 @SiO 2 core/shell
2 g of Fe 2 O 3 spindles were first dispersed in a solution consisting of 400 mL of ethanol and 100 mL of water and sonicated till dispersion. 10 mL of ammonia were then added to the suspension followed by 6 mL of TEOS under constant magnetic stirring. The mixture was left for 4 h at 25 °C. The formed Fe 2 O 3 @SiO 2 core/shell was obtained by centrifugation and washed with ethanol and water repeatedly [26] Fig. 1.

Synthesis of Fe 2 O 3 @SiO 2 /In 2 O 3 nanocomposite
This nanocomposite was prepared as follows. 1 g of indium nitrate hydrate, 1 g of urea, and 0.5 g of Fe 2 O 3 @SiO 2 were mixed in 200 mL of ethyl alcohol and stirred for 40 min. The mixture was transferred into a 100-mL Teflon-lined stainless steel autoclave and maintained at 180 °C for 2 h, followed by 160 °C for 8 h. After that, the autoclave was left to cool to ambient temperature. The obtained material was centrifuged and washed with water and absolute ethanol. It was then dried at 80 °C for 12 h and calcined in air at 400 °C for 2 h. [27] Fig. 1.
Phenyl hydrazine (0.76 g, 7 mmol) was added to (1.29 g, 6.8 mmol) of 3-(4-nitrophenyl)-3-oxopropanenitrile in absolute ethanol (5 mL) and acetic acid (0.2 mL). The reaction mixture was refluxed for 10 h, and the excess solvent was removed under reduced pressure. The crude product was crystallized from ethanol to give the compound 1 in Fig. 2

Synthesis of substituted chalcones (2a-c)
The investigated chalcones (2a-b) are synthesized according to Claisen-Schmidt condensation [28]. Equimolar concentrations (1.21 g, 10 mmol) of 1-(pyridine-2-yl) ethanone and respective aldehydes (10 mmol) were mixed and dissolved in a water-ethanol mixture (30%, v/v) (30 mL). To this solution, 20-mL aqueous sodium hydroxide solution (20%) was added dropwise with stirring, and the reaction mixture was kept under stirring overnight at room temperature. Completion of the reaction was identified by observing thin layer chromatography (TLC) on pre-coated SiO 2 gel plates. After completion of the reaction, the reaction mixture was poured into crushed ice, and acidified with dilute HCl till the chalcones were precipitated out as solid. The solid separated was filtered off and dried. It was purified by recrystallization from ethanol Fig. 3. Reaction progress was monitored by TLC using benzene/ethyl acetate (3/1 by volume) as eluent. The 5-(4-(dimethylamino)phenyl)-1-(pyridine-2-yl)penta-2,4-dien-1-one (2c) was prepared according to the previously reported method [29]. The obtained chalcones are:

Results and discussions
Catalyst characterization

FT-IR
The FT-IR spectrum of the Fe 2 O 3 spindles was recorded in the range of 400-4000 cm −1 . The large broad peak at 3453 cm −1 is ascribed to the O-H stretching vibration of OH groups. The absorption peaks around 1630, and 1382 cm −1 are due to the asymmetric and symmetric bending vibration of the C = O of the PVP stabilizing agent, indicating the formation of a PVP layer on the surface of spindles [25]. The band at 577 cm −1 is corresponding to the Fe-O stretching mode of Fe 2 O 3, Fig. 5a [32]. For Fe 2 O 3 @SiO 2 , in addition to the previous band that appeared in the spectrum of Fe 2 O 3 spindles, the new band around 1085 cm −1 is attributed to the symmetric and the asymmetric stretching vibration frequency of Si-O-Si, indicating  Fig. 5b [27]. The intense peaks at 590, 553, and 440 cm −1 correspond to the In-O phonon vibration mode which is characteristic of In 2 O 3 as shown in Fig. 5c [14,33].

EDX
The energy-dispersive X-ray signals provide information on the sample composition. EDX spectra of the synthesized Fe 2 O 3 spindles, Fe 2 O 3 @SiO 2 core/shell, and Fe 2 O 3 @SiO 2 /In 2 O 3 nanocomposite are shown in Fig. 8 where their tentative data are collected in Table 1 Figure 9a shows the morphology of the spindle-like particles of Fe 2 O 3 . The particles have an average length of 600 nm and width of 220 nm uniform and a continuous PVP layer appeared on the surface of the spindles, indicating that the obtained spindles are coated with the PVP. Figure 9b describes the TEM micrograph of the Fe 2 O 3 @SiO 2 core/shell. It demonstrates that the Fe 2 O 3 spindle core is covered with a SiO 2 shell. In 2 O 3 nanoparticles are present on the surface of the    the SiO 2 -coated spindles in Table 2 have not changed in comparison with the corresponding values of uncoated Fe 2 O 3 . Coating of Fe 2 O 3 with the SiO 2 reduces the value of Ms. Thus, the coated samples can easily be separated from the reaction mixture with an external magnet. Since the units of the magnetization are reported per gram of material, such a decrease in Ms would reflect a smaller percentage of net magnetic material per gram of the overall sample [40,41].

Characterization of reaction products 3a-c
The azomethine compounds based on 5-amino-pyrazoles have been synthesized by two different methods, conventional and catalytic. The key start 3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-5-amine (1) was synthesized in two steps: the first step is the reaction of sodium cyanide with 2-bromo-1-(4-nitrophenyl) ethanone to produce 3-(4-nitrophenyl)-3-oxopropanenitrile which is confirmed by the appearance of a nitrile absorption peak at 2255 cm −1 . This product reacts in the second step with phenyl hydrazine in absolute ethanol and acetic acid as given in Fig. 11. The structure of compound 1 was identified by FT-IR, 1 HNMR, 13 CNMR, and mass spectrometry. The disappearance of the nitrile absorption peak in the FT-IR spectrum and the Fig. 11 A proposed mechanism for the conventional synthesis of azomethine compounds 3a-c appearance of new broad bands at 3421 cm −1 and 3303 cm −1 due to the amino group supports the formation of this compound. The 1 HNMR spectrum exhibits a characteristic methine proton (=CH of pyrazole ring) as a singlet at δ 5.58 ppm, an amino proton at δ 5.22 ppm which are exchangeable by mixing with D 2 O, and multiple at δ 7. 22-8.36 ppm that corresponding to aromatic protons. The 13 CNMR spectrum of compound 1 has signals at δ 86.48, 146.79, and 148.46 ppm, indicating the presence of C 3 , C 4 , and C 5 of the pyrazole ring, respectively. Furthermore, the formation of compound 1 has also been confirmed by mass spectra that match its molecular weight. The starting compound 3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-5-amine (1) was condensed with chalcones derivatives 2a-c by one-pot two-component systems in the presence of sulfuric acid to yield the corresponding compounds 3a-c (conventional method) or in the presence of Fe 2 O 3 @SiO 2 /In 2 O 3 nanocatalyst (catalytic method) as shown in Fig. 12. The characteristic spectral analysis of FTIR, 1 HNMR, 13 CNMR, and mass spectra used to confirm the structures of the synthesized compounds are provided in the supplementary file (Figs. S1-S4).
The first reversible step of the mechanism of azomethine formation is the nucleophilic attack of the amine group on the electrophilic carbonyl carbon of the aldehyde to form an imine. The formation of azomethine from an imine depends largely on the water removal rate in the final step.
Depictions of compounds 3a-c were established based on their elemental analyses and spectral data (FTIR, 1 H, 13 CNMR, and MS). The FT-IR absorption bands of the compounds 3a-c appeared at 1600-1673 cm −1 for the C=N pyridine ring , and 1510-1517 cm −1 are due to azomethine group C=N-and the 1440-1510 cm −1 are due to the CH=CH aliphatic for compounds 3a-c, respectively. The 1 H NMR spectra revealed doublet signals at range δ 7.57-7.62 ppm which are due to the CH=CH. The doublet signals at range δ 6.72-7.75 ppm are attributed to the CH=CH for the compounds 3a-c. For the compound 3c, the singlet signal at 2.87 ppm is due to N-CH 3 , the doublet signals at δ 6.61 ppm are characteristic of the CH=CH, and the doublet signals at δ 6.89 ppm are assignable to the CH=CH. The signal of the free NH 2 protons is absent in the spectra of azomethine compounds 3a-c indicating their formation. All other protons are located at their respective positions. 13 C NMR spectra of compounds 3a-c showed signals at δ 123.5-131.1 that belong to the (CH=CH), signals at δ 139.3-147.5 correspond to the (CH=CH), the signals at δ 156.2-157.9 are due to (C=N imine ), the signals at δ 157.7 are attributed to the (C=N of pyridine ring). The number of signals found are corresponding to the magnetically nonequivalent carbon atoms. Moreover, the mass spectra of the azomethine compounds 3a-c displayed peaks at m/z which match their exact molecular mass. Details of selected spectroscopic data are reported in the experimental section.

Comparative synthesis of compounds 3(a-c), comparative study
Many studies on the synthesis of azomethine compounds have been reported [42,43], but they all suffer from one or more serious shortcomings, such as high environmental pollution due to the solvent and reaction hardness, high temperature, multistep pathways, and long reaction times with low-to-moderate yields under severe reaction conditions. Recently, one of the most intriguing areas in the synthesis of widely used organic compounds is the focus on benign environmentally friendly conditions and reagents such as catalysts. The catalysts have played vital roles in reducing the pollution of our environment. In addition, the catalyst can be recycled from the liquid reaction medium and reused, to maintain the high productivity of reaction products [44,45].
In this regard, we studied the condensation reaction between 3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-5-amine (1) and chalcones derivatives 2a-c by one-pot twocomponent systems using the heterogeneous nanocatalyst, Fe 2 O 3 @SiO 2 /In 2 O 3 to synthesize a series of 3-(substituted)-1-(pyridine-2-yl) allylidene)-3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-5-amine derivatives 3a-c. The desired products were obtained with high yields in short reaction times. The suggested mechanism offers the removal of water by the dehydration strategy [46]. The Fe 2 O 3 @SiO 2 /In 2 O 3 catalyst was used as a dehydrating agent for the conversion of the imine into the corresponding azomethine products. The reaction is facile due to the good electrophilic and nucleophilic properties of the carbonyl and amine groups, respectively. The comparative results are depicted in Table 3. The results showed that the synthesized compounds by different techniques have the same properties [TLC, melting point, and mixed melting point] with more cleanly and high yield in the case of the catalytic method than the conventional one. The comparison of the results obtained from the Fe 2 O 3 @SiO 2 /In 2 O 3 catalyzed method with some of the reported catalysts used for the synthesis of Schiff bases shows the high efficiency of the Fe 2 O 3 @SiO 2 /In 2 O 3 catalyzed method. This is due to the good yield and the short reaction time as given in Table 4.

Recycling of nanocatalyst
To examine the reusability of Fe 2 O 3 @SiO 2 /In 2 O 3 nanocatalyst, it was magnetically recovered from the reaction mixture and reused for fresh subsequent experiments under the same reaction conditions. It is interesting to know that the yields remained approximately constant during all the experimental runs as illustrated in Fig. 13. The recyclability and reusability of the catalyst have been established without a significant loss of its activity. The stability of the catalyst after the first three cycles has been examined by the analysis of the reused catalyst with FTIR, XRD, SEM, and are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.