Preparation and Characterization of Hollow MgO/SiO2 Nanocomposites and Using as Reusable Catalyst for Synthesis of 1 H-isochromenes

In the present study, a hollow MgO/SiO2 nanocatalyst with high alkaline properties was prepared. This heterogeneous catalyst was prepared in several steps to create a great active area and decrease the density of the catalyst. The alkaline hollow catalyst framework was applied for the reaction of cyclohexanone, malononitrile and benzaldehyde for synthesis of 1 H-isocromene therough the Michael addition and aldol condensation reaction at room temperature. In this method, all of the done reactions were excellent in the yields of products and reaction times. At the end of the reaction, the nanocatalyst separated by simple filtration and reuse in several runs elsewhere. In the present study, hollow MgO/SiO2 nanocatalyst with great base properties was made. Thisheterogeneous catalyst was a synthesis in several steps to create a great active area and decreasethe density of the catalyst


Introduction
The 1 H-isochromene derivatives are a special structural style commonly appearance in a numerous of naturally and nonnaturally products [1][2][3][4] which has represented as "advantaged structure" in various medicinally and related compounds due to its significant biological effects counting antitumor properties [5][6][7][8]. Some natural compounds that include the isochromene were flaccidin separated of the orchids, Dendrobium amoenum also Coelogyne flaccida and also the numerous of compounds which separated from Cannabis sativa, can be observed as isochromene derivatives [9]. Three derivatives of Ulmusdavidiana which comes from Korea are utilized in oriental medicines for the usage of edema, inflammations, and stomach cancer. The enormous value of these compounds have inspired much effort to advance a vast number of influential and dependable procedures for their syntheses [10]. Outdated 1 H-isochromene synthesized from dimerization of benzopyrylium salts in acid conditional [11]. The shortage of substrate range and the trouble in the supply of benzopyrylium salts was a disadvantage for this method. For solving this problem, the direct and economical ways have been established to the synthesis of 1 Hisochromenes via different catalysts such as transition-metalcatalyzed and organic functional catalyzed.
The preparation of solid heterogeneous nanocatalyst with exact control the site of unique functionalities was commonly required in the organic reaction. In contrast, the solid catalysts attended with lacking clear morphology such as the hollow compounds with small density and the great explicit surface area. Hollow catalyst and nanoparticles wall, hollow spheres via nanometre or micrometre dimension often display singular chemical and physical properties dissimilar from dense particles.
Hollow spheres have used in many fields, for example electrics, light-weight filler, optics selective adsorption, magnetics, drug delivery, medicine-release capsules, and catalysis [12][13][14][15][16][17]. Consequently, there has been abundant interest in arranging hollow compound with altered arrangements in latest years. In earlier reports, the hollow structure with amorphous shells or nanocrystalline and hard template or soft Highlight • The hollow MgO/SiO2 nanocatalyst was used as active base catalyst.
• The products were characterized using melting point, FT-IR and 1 H NMR techniques.
• The products were obtained in excellent yields and short reaction times.
• The hollow MgO/SiO 2 nanocatalyst as efficient catalyst was employed in synthesis of 1H-isocromenes. template were ready in diversity courses. In the hard template structure, the first coating is formed on the core and then the hard template (core) is eliminated by chemical or thermal method to form hollow structure. To fabricate hollow spheres variability of solid particles have been utilized as hard templates like polystyrene spheres, silica particles, carbon spheres [18][19][20][21][22]. The hard template technique is the great method for the construction of hollow spheres: hollow spheres with altered dimensions can be attained by the usage of colloid particles with a particular size, and the thickness wall of hard template hollow particles is due to reaction restrictions. In the soft template method, regularly usage of emulsions, vesicles, and micelles molecules which formed via self-assembly to template [23][24][25][26][27].
In this research, it was prepared the hollow MgO/SiO 2 nanoparticles with the great surface active alkaline area and used in the reaction of cyclohexanone, malononitrile and benzaldehyde for synthesis of 1 H-isochromene under mild condition.

Chemicals
All material and solvents were used as the starting resources attained without further purification. Also, cyclohexanone, malononitrile, benzaldehyde, cetyltrimethyl ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS) and ammonium aqueous solution, were acquired from Sigma. Magnesium oxide, sodium bicarbonate, ammonium peroxydisulfate and hydrogen chloride, were purchased from Sinopharm Chemical.
The products were recognized with melting point, FT-IR and 1 H NMR analysis, the spectra were recorded in DMSOd 6 and CDCl 3 solvents and register on a Bruker DRX-400 spectrometer via tetramethylsilane as the inner reference. FT-IR spectra were attained via KBr pellets and record with Perkin-Elmer 781 spectrophotometer by an Impact 400 Nicolet FT-IR spectrophotometer. XRD analysis was recorded with (CuKa, radiation, ʎ = 0.154056 nm), with the speed of 2°min − 1 beginning 10°to 80°(2 ). The nanocatalyst size was determined with Zeiss Scanning Electron Microscope (SEM) worked at a 15 kV accelerating voltage. The surface areas (BET) were assignment via nitrogen adsorption-desorption in − 196 o C that recorded by analyser Tristar 3020, Micromeritics.

Synthesis of Compact SiO 2 Spheres (sSiO 2 )
For a synthesis of sSiO 2 from Stober procedure, 5 mL of tetraethylorthosilicate was instantly added to the mixture of deionized water (8 mL), ethanol (70 mL) and ammonium aqueous solution (28 %, 4 mL). Then, the mixture was stirred for 1.5 h in ambient temperature. At the end of the reaction, the white silica suspension was formed, then the product separated with a centrifuge and washed three times by deionized water and ethanol.

Synthesis of Hollow SiO 2
60 mg of the prepared sSiO 2 was dispersed in 15 mL deionized water via the ultrasonic waves for 20 min. Then, 1.5 mL of the CTAB aqueous solution (1 mg, 1.5 mL) was added and stirred the mixture at ambient temperature for 1 h. Then, 212 mg of Na 2 CO 3 added to the reaction mixture and followed the reaction at 35°C for 24 h. At the end, the product has separated and washed with deionized water and ethanol.
2.4 Synthesis of hollow SiO 2 /MgO by Self-Assembly 50.0 mg of hollow SiO 2 was dispersed in 5.0 mL toluene by ultrasonic water bath for 30 min. After that, 2.0 mL of the MgO NPs which dispersed in toluene was added to the mixture and sonicated for 1.5-2 h. Consequently, the product was washed by toluene and dried at 120°C overnight.

Preparation of Hollow SiO 2 /MgO
The product of previous steps was converted to hollow MgO/ SiO 2 with hydrothermal removal of CTAB phase in 450°C for 4 h. As a result, the hollow MgO/SiO 2 were prepared.

General Procedure for Multicomponent Synthesis of 1 H-isochromene
1 H-isochromene was synthesized from the three-component reaction. In this reaction, 1 mmol of cyclohexanone (1a-d) with 1 mmol of malononitrile were mixed in ethanol solvent. Then, 10 mg of hollow MgO/SiO 2 nanocatalyst was added to the mixture and stirred for 10-20 min at room temperature. After completed the first step, 1 mmol of benzaldehyde was added to the mixture and the reaction followed for 10-20 min at room temperature. In the end, the nanocatalyst was separated by simple filtration and added water (5 ml) to the mixture for the formation of the pure product. The final product was characterized by melting points, IR and 1 H NMR spectra. 3-amino-

Design of Experiments
The experimental conditions and the importance of the objective parameters and their interaction were optimized and followed by the Box-Behnken design (BBD) method. Firstly, several tests were performed to choose the effective factors and their ranges for the yield of the product.
In this investigation, the catalyst amount (A), temperature (B), and time of reaction (C) were chosen as variables. Each data variable was placed at three levels: -1, 0, and + 1. The three various levels of the variables and experimental ranges were displayed in Table 1.
The number of examination runs was measured according to the following equation: In this equation, No is the number of central points, and k is the independent factors. In this research, three independent variables and three focal points were used, so the total number of the test was 15 runs. The obtained data and design matrix were displayed in Table 2. Analysis of the variance (ANOVA) was determined to the efficacy of the fitted model. Design-Expert 10 (Stat-Ease Inc., USA) was applied to analyze the final data and design the experimental runs.

Preparation and Chracterization of Catalyst
In this research, it was needed a strong base as a catalyst to obtain the 1 H-isochromene derivatives with excellent yields and short reaction times. The MgO is the strong base, but the yield of the model reaction at the presence of this catalyst was 79 % (Table 1. Entry 9) in the mild condition. So to increase the basicity of the MgO, it was designed the novel nanocatalyst that includes a large surface area covered with base compound. The hollow compounds, because of numerous pore and hollow spaces, have a great surface area. So, the hollow compounds were designed that contain mesopore silica and covered with MgO. The model reaction was investigated with the novel catalyst and achieved an excellent yield of the product. In this research, the hollow MgO/SiO 2 nanoparticles were prepared in three-steps that show in Scheme 1. At the first step, compact SiO 2 sphere (sSiO 2 ) was prepared and decreased density and increased of the active area space via converted to hollow SiO 2 [29,30]. Then, the hollow SiO 2 was functionalized with MgO nanoparticles and the obtained nanostructure calcinated and converted to the hollow MgO/ SiO 2 nanocatalyst.
After preparation, the nanocatalyst was characterized by various analysis such as; FT-IR, XRD, BET, SEM and TEM. For the determined the crystal structure of nanoparticles, the X-ray diffraction patterns of nanostructure were investigated with the XRD spectrum (Fig. 1). In the graph (a), the structure of hollow SiO 2 considered by X-ray diffraction (XRD) (tetragonal, JCPDS card N 34-0425). The spectra were showed a wide peak in 20-30 that assignment an amorphous structure of SiO 2 (Fig. 2). The graph (b) that due to hollow MgO@ SiO 2 furthermore the wide peak in 20-30, it has two peaks in 43, 62 that due to MgO (Fig. 2).
The hollow catalyst was considered by FT-IR spectrum (Fig. 2). Figure 2a  The hollow structure of synthetic compound has been demonstrated. The N 2 adsorption-desorption isotherms and hysteresis loop provided better confirmation of the mesoporous structure. The Brunauer-Emmett-Teller (BET) was demonstrate 619 m 2 g − 1 surface area and the mean pore diameter is 2.11 nm (Fig. 3).
Hollow spheres morphology was achieved after calcination and considered by FE-SEM. The SEM images have displayed the formation of hollow MgO/SiO2 nanoparticles with smooth and regular morphology in two scales 200, (Fig. 4a) and 500 nm (Fig. 4b). The images were displayed the average crystal size of the nanocatalyst between 110 and 170 nm that measured with Digimizer software. The morphology of the nanocatalyst was regular spherical and uniform.
To discover the morphology of hollow MgO/SiO 2 nanoparticles, transmission electron microscopy (TEM) was employed. The TEM image of the nanoparticles illustrates the formation of a hollow MgO/SiO 2 nanostructure that contains an empty space at the core and the MgO/SiO 2 on the shell of the molecule (Fig. 5). The regular morphology was a display in two scales 30 nm, (Fig. 5a) and 50 nm (Fig. 5b). The morphology of the nanocatalyst was regular spherical and uniform. The size of the nanoparticle was calculated with Digimizer software and display the size of hollow space in the core of the nanocatalyst is double of the shell.
The TG curve of hollow MgO/SiO 2 displayed weight loss data from 30 ºC to 1100 ºC. A complete weight loss was around 14 % and chiefly occurred through 30-100 ºC, matching to the adsorbed water. The DSC curve varied with the TG curves recommending that each mass reduction processor reacts to an endothermic process (Fig. 6).

Investigation of Catalytic Activity
1H-isochromene was synthesized from cyclic ketones, malononitrile and benzaldehyde in varies conditions. The model reaction was investigated with different catalysts, the amount of catalyst and solvents moreover the result displayed in Table 3. Some various acids and bases as the catalyst were examined in the model reaction. These catalysts were P-TSA, nanoNiFe 2 O 4 , Nano CoFe 2 O 4 , guanidine, morpholine, MgO, nanoCaO, Et 3 N, nanoMgFe 2 O 4 , and Hollow MgO/SiO 2 ( Table 3). The observation of low productivity in a long time was noticed in the presence of acidic catalysts, such as; P-TSA, nanoNiFe 2 O 4 , and Nano CoFe 2 O 4 (Table 3, entries 2, 3). It was revealed that the yield of product in the model reaction improved under the influence of nitrogen containing bases such as; guanidine, triethylamine, morpholine, similarly MgO, CaO, MgFe 2 O 4 as a Lewis base catalyst. The MgO is a strong base, but the yield of the model reaction in the presence of this catalyst was 79 % (Table 3. Entry 9). The yield of the reaction using Hollow MgO/SiO 2 was investigated and determined, it has the greatest yield in the short reaction time (Table 3. Entry 10). Also, the type of solvent was investigated in   Table 1, Entries 10-14. The ethanol was selected as the best solvent for the model reaction (Table 3. Entry 10).

Statistical Analysis
The resulting model was achieved from BBD is quadratic and correlates the yield of products as a function of catalyst amount (A), temperature (B), and time of reaction (C). AB, AC, and BC display double cooperations, and A2, B2, and C2 are the quadratic outcomes. The statistical analysis was obtained with a 95 % confidence level.
Yield % ð Þ ¼ þ93:00 þ 4:50 Â A À 4:50 Â B þ 0:50 To study the efficacy of the model and the significance of major variables, it was performed the analysis of variance (ANOVA) method. The acquired results were shown in Table 4. As a result, the term A (catalyst amount) with a smaller p-value and a larger F-value was the most significant agent in the increase of the yield reaction, whereas the term According to the results, The F-value of the model 5.84, and the p-value of 0.0013 are proved the validity of the model. Also, the p-value of lack of fit was 0.5456 and not significant, noting that the model fitted has great experimental data. Furthermore, the validity of the model was founded by the high values of the predicted R 2 (98.78 %) and adjusted R 2 (99.46 %).

Effect of Independent Variables and Their Interactions on the Yield of Product
To compare the influence of chief independent variables on the yield of the product was used the perturbation plot, which can see in Fig. 7. All parameters have a significant influence on the yield of the product. Although, the effect of time was less than the catalyst amount and temperature. Figure 7a-c the response surface plots were incarnated from Eq. (2). Figure 7a displays the influence of catalyst amount and temperature at a constant time on the yield of the product. It was obvious, an increase in catalyst amount and  decrease in temperature can be raised the yield of the product. The interaction between catalyst amount and time was shown in the Fig. 7b. As the result, the yield of the reaction increased by rising catalyst amount and half of the time. The interaction between temperature and time was investigated and the result, displaying in Fig. 7c. It is clear that at low temperature and half time, the yield of the reaction increased. After optimization of the reaction conditions with different catalysts and solvents, the situation of a reaction was determined (Scheme 2). The hollow MgO/SiO 2 with strong base properties selected as the catalyst for the synthesis of 1 H-isochromene from cyclohexanone (1 mmol), malononitrile (1 mmol) and benzaldehyde (1 mmol) in the ethanol solvent. Therefore, the different derivatives of 1 H-isochromene (Table 5) were synthesized at room temperature in 20-30 min.
In this reaction, the 1H-isochromenes derivatives with electron-donating and electron-withdrawing substituents were achieved as pure products in excellent yields and short reaction times (Table 5).   Table 5 The reaction of cyclohexanone 1a-d, malononitrile and benzaldehyde 3a-h for synthesis of 1H-isochromenes 4a-l a

Proposed Reaction Mechanism
Synthesis of 1 H-isochromene was done in the two-step; the first step including the mixed of cyclohexanone with malononitrile in ethanol under the base condition. The reaction was followed by vinylogous Michael addition for the synthesis of vinylmalononitriles. In the second step, the benzaldehyde was added to the mixture and during the aldol condensation reaction, vinyl malononitrile reacted with benzaldehyde. The vinyl malononitrile was adsorbed a hydrogen, and the processes followed by cycle creation of C-C and C-O bonds. In the end, 1 H-isochromene was synthesized with loss of the hydrogen via the base catalyst [31] (Scheme 3).

Catalytic Comparisons
The efficiency and influence of new methods were investigated by the comparison of other methods, catalysts, and conditions ( Table 6). As can be seen, the present study with novel nanocatalyst is superior in the yield of pure products and short reaction times.

Reusability
At the end of reaction, the hollow catalyst separated by simple filtration and washed with acetone and ethyl acetate solvent. The heterogeneuse nanostructure can be catalyze the reaction in six consecutive runs without loss of activity (Fig. 8).

Conclusions
In this research, it was prepared a novel heterogeneous hollow catalyst for the synthesis of 1 H-isochromene from cyclohexanone, malononitrile, and benzaldehyde. The reaction was followed in the ethanol solvent at room temperature and hollow MgO/SiO 2 nanostructure used as a base catalyst. The products were synthesized in excellent yields and short reaction times. The catalyst easy recovered and reused for several runs of the reactions.
Scheme 3 Proposed reaction mechanism for the synthesis of 1H-isochoromene