Guanidinylated SBA-15/Fe3O4 mesoporous nanocomposite as an efficient catalyst for the synthesis of pyranopyrazole derivatives

In this study, a novel mesoporous nanocomposite was fabricated in several steps. In this regard, SBA-15 was prepared by the hydrothermal method, next it was magnetized by in-situ preparation of Fe3O4 MNPs. After that, the as-prepared SBA-15/Fe3O4 functionalized with 3-minopropyltriethoxysilane (APTES) via post-synthesis approach. Then, the guanidinylated SBA-15/Fe3O4 was obtained by nucleophilic addition of APTES@SBA-15/Fe3O4 to cyanimide. The prepared nanocomposite exhibited excellent catalytic activity in the synthesis of dihydropyrano[2,3-c]pyrazole derivatives which can be related to its physicochemical features such as strong basic sites (presented in guanidine group), Lewis acid site (presented in Fe3O4), high porous structure, and high surface area. The characterization of the prepared mesoporous nanocomposite was well accomplished by different techniques such as FT-IR, EDX, FESEM, TEM, VSM, TGA, XRD and BET. Furthermore, the magnetic catalyst was reused at least six consequent runs without considerable reduction in its catalytic activity.

Porous materials with remarkable characteristics such as high surface area, well-defined porous structure, uniform pore size, and processability have attracted great interest from researchers in scientific fields 1,2 . Based on the IUPAC definition, the porous materials are classified in three main groups depending on their pore size (or pore width): microporous (pores width < 2 nm), mesoporous (2 < pores width < 50 nm), and macroporous (pores width > 50 nm) materials 2,3 . In 1998, Stucky and et al. synthesized a novel kind of hexagonal array of pores named SBA (Santa Barbara Amorphous). After that, different types of SBA materials such as SBA-1, SBA-16 and SBA-15 have synthesized. The SBA-15 is a highly ordered mesoporous materials with striking properties for instance high surface area, straight cylindrical pores, thick framework walls, adjustable pore size , large pore diameter (which provide a facilitated diffusion of reactant molecules), and excellent ability to be modified/functionalized. It has been extensively utilized in various application such as catalysis 4 , removal of pollutants form wastewater 5 , hyperthermia 6 , drug delivery 7,8 , and chromatographic techniques 9 . To obtain high performance SBA-15-based catalysts, the surface functionalization or modification needs to be performed. There are two main approach to modify/functionalize the silica-based mesoporous materials including one-pot synthesis or co-condensation and grafting technique or post-synthesis. In the first approach, the active phase is added to the reaction mixture which subsequently co-assembles into the inorganic framework for the construction of the mesoporous material in single step, but in the second approach siliceous support is prepared followed by the modification with active moieties or their precursors 2,10,11 . Incorporating Fe 3 O 4 MNPs as a superparamagnetic material into the silica-based mesoporous materials is a practical way to achieve retrievable and reusable nanocomposite with enhanced surface area 12 . The chemical modification of SBA-15 gives high efficiency porous catalyst by more active sites to interact with reactants. In recent years, a great attention has been dedicated to prepare amine functionalized SBA-15 to enhance its potential catalytic application. For instance, several types of amines functionalized SBA-15 were fabricated via grafting technique by using three different aminosilane reagents then, it was applied as heterogeneous catalysts for Michael addition 13 . One of the most widely used materials to modify the SBA-15 through both co-condensation or and post-synthesis is the 3-aminopropyltriethoxysilane (APTES) 14,15 .
Guanidine, the nitrogenous analogue of carbonic acids, is a fascinating group of basic organic compounds. They are exceedingly strong Brønsted and Lewis bases, their basic strength more than amines, pyridines, diamines and amidines. This strong basicity is ascribed to great delocalization of positive charge on the guanidinium cation above the three nitrogen atoms. After protonation of guanidine group, the highly stable guanidinium ion act as a bidentate hydrogen bond donor which able to activate different hydrogen bond acceptors species such as carbonyl groups 16,17 . Therefore, guanidine and their derivatives can be considered as appropriate candidates in base-catalyzed organic reactions. The guanidinylation reaction has been used to convert primary amine groups in different materials for example chitosan 18,19 and Poly(2-guanidinoethylmethacrylate) 20 into guanidine groups. Multicomponent reactions (MCRs) are one of the most significant methods for the synthesis of heterocyclic compounds because of their outstanding properties such as high atomic economy, short reaction time, straightforward reaction model, high selectivity, and great compliance with principals of green chemistry [21][22][23] . Among the product of MCRs, the pyranopyrazole derivatives have received much interest of researchers due to their extensive application in pharmacology and medicine [24][25][26][27] . In continuation of research on heterogeneous nanocatalysts [28][29][30] , in this study a novel SBA-15 based nanocomposite prepared in four steps as illustrated in Fig. 1a, then it was used as a heterogeneous catalyst in the synthesis of dihydropyrano [2,3-c]pyrazole derivatives via four component condensation reaction (Fig. 1b).

Experimental
General. All the required chemical reagents and solvents were purchased from the chemical international companies including Merck and Sigma Aldrich. Several analyses were carried out to demonstrate the construction of the catalyst. Fourier-transform infrared (FT-IR) spectra were carried out by applying a Shimadzu IR-470 spectrometer by using KBr pellet. Elemental analysis of the prepared samples was performed by energy dispersive x-ray analysis (EDX) recorded on Numerix JEOL-JDX 8030 (30 kV, 20 mA). X-ray diffraction (XRD) pattern of fabricated samples were obtained by X-ray diffractometer (Bruker D8 Advance). The morphology and surface of samples were studied by a field emission scanning electron microscope (FESEM) and transmission electron microscopies (TEM) using VEGA2 TESCAN instrument and Zeiss-EM10C-100 kV, respectively. The magnetic behavior of samples was measured using VSM analysis (Meghnatis, daneshpajooh Kashan), and thermal stability of samples was studied by thermogravimetric analysis (TGA) using a BAHR-STA 504 instrument. Melting points of synthesized products were measured with an Electrothermal 9100 apparatus. The specific surface area of prepared samples was determined using the Brunauer-Emmett-Teller (BET, Micrometics ASAP2020). 1 HNMR and 13 C NMR nuclear magnetic resonance spectra were recorded on a Bruker DRX-500   The reaction completion process was investigated by thin layer chromatography (TLC). After completion of the reaction, hot ethanol was added to dissolve the product, then undissolved magnetic mesoporous catalyst was separated from the reaction mixture by a magnet and filtration. The crude products were recrystallized from EtOH to obtain pure dihydropyrano[2,3c] pyrazole derivatives.
Spectral data of selected products. 6

Results and discussion
Characterizations. In  www.nature.com/scientificreports/ mesoporous catalyst, several spectral and analytical techniques were employed which will be explained and discussed.
FT-IR spectroscopy. FT-IR analysis was used to detect different functional groups in the samples fabricated in each step. As is observed in Fig Transmission and Scanning Electron Microscopies (TEM, SEM). Field emission scanning electron microscopy was employed to observe particle size distribution, surface morphology and particle aggregation mode in prepared samples. As is observed in Fig. 4, the FESEM images of guanidinylated SBA-15/Fe 3 O 4 and SBA-15 are presented in three scales: 1 µm, 500 and 200 nm. The SBA-15 images presented a porous structure, but in the nanocomposite images in addition to the porous structure, the distribution of spherical Fe 3 O 4 MNPs on the SBA-15 as a mesoporous support was also can be observed. Therefore, fabrication Fe 3 O 4 MNPs onto SBA-15 mesoporous matrix and subsequent modification resulted in change the its morphology. The average particle size for 35 spherical particles in the nanocomposite was determined to be about 26 nm using Digimizer software. TEM analysis was performed to more accurately study the morphology and particle size of the mesostructured guanidinylated SBA-15/Fe 3 O 4 catalyst. As can be seen in Fig. 5, TEM image of prepared nanocomposite (left image of Fig. 4c) exhibited an ordered pore channels framework having dimension about 6-7 nm. In another image (right image of Fig. 4c), both a regular mesoporous arrangement with two-dimensional hexagonal honeycomb structure and the Fe 3 O 4 MNPs onto SBA-15 support was observed, but formation of the magnetite NPs onto the certain amount of SBA-15 channels and subsequent functionalization lead to hide some part of ordered pore arrangement.  According to the reported information, SBA-15 has high thermal stability; it has maintained above 90-95% of its weight up to 700 ºC and a continuous slight weight loss was attributed to dehydrogenation or dehydroxylation of its surface 38,39 . Moreover, the thermal behavior of Fe 3 O 4 displayed that with increasing the temperature to 800 °C, a small weight loss of about 5-6% was occurred, which was ascribed to the evaporation of water molecules absorbed in it 40 . As can be observed in Fig. 6, the thermogram of the SBA-15/Fe 3 O 4 (a) exhibited a gradual gentle weight loss between 50 and 800° C which may be related to the evaporation of adsorbed water molecules in the cavities of this sample, and dehydrogenation or dehydroxylation of its surface. Therefore, high thermal stability of this composite was demonstrated with just 9% weight loss until 800 °C. In the thermogram of guanidinylated SBA-15/Fe 3 O 4 nanocomposite (b), the first observed weight loss (~ 2%) in the temperature range of 50-160 °C is attributed to the evaporation adsorbed water molecules in the cavities and surface of the mesoporous nanocomposite. Next, with increasing temperature to 550 °C weight loss of about 10% occurs, which can be due to the separation and thermal decomposition of organic parts (alkyl chain and guanidine group) that covalently bounded to the SBA-15/Fe 3 O 4 , and the continuation of weight loss with increasing temperature up to 800 °C can be ascribed to the condensation of silanol groups of guanidinylated SBA-15/Fe 3 O 4 41 . The residual weight of these mesoporous nanocomposites up to 800 °C is about 85%, which is only 6% more weight loss than the SBA-15/Fe 3 O 4 compound. Therefore, it can be referred that the two steps chemical modification of SBA-15/Fe 3 O 4 did not have a significant effect on its thermal resistance. Furthermore, considering the difference in residual weight of the two samples, it can be calculated that just about 6% of the total weight of the guanidinylated SBA-15/Fe 3 O 4 nanocomposite composed of the organic part. The differential thermogravimetric analysis (DTGA) of guanidinylated SBA-15/Fe 3 O 4 (spectrum c) showed main endothermic peaks at 123 and two weak peaks at 411 and 510, the first one is attributed to the loss of adsorbed water molecules in mesoporous nanocomposite and the others related to decomposition of the organic part which constitute a very small weight percent of nanocomposite and the condensation of silanol groups of SBA-15. It can be seen from these results that the prepared mesoporous nanocomposite has structural stability at high temperatures and can be used for catalytic reactions at high temperature.
XRD analysis. The XRD analysis was used to investigate the crystalline nature of prepared samples. As is depicted in Fig. 7, the XRD pattern of SBA-15 (b) showed a broad characteristic peak at 2Ө: 20-30 34,42 .The diffractogram of guanidinylated SBA-15/Fe 3 O 4 (c) exhibited the relatively broad peak at 2Ө: 20-30° with attributed to the presence of SBA-15, which was lower intensity compared to unmodified SBA-15, this reduction can     Fig. 9. All samples exhibited a typical type-IV curves which are characteristic of mesoporous materials. However, the magnetic nanocomposites exhibited narrower hysteresis cycles than the SBA-15 and their adsorption and desorption branches are closer which can be related to an increase in their pore diameters, as can be seen in Fig. 9(I). The surface area, the pore volume and pore size (width) were calculated by the BET (Brunauer-Emmett-Teller) and BJH (Barrett-Joyner-Halenda) methods and results are summarized in Table 1   To obtain the best result, different experimental conditions such as temperature, solvent, amount of catalyst and the type of catalysts was examined in the one-pot four components reaction of ethyl acetoacetate (1 mmol), hydrazine hydrate (1.2 mmol), 3-nitrobezaldehyde (1 mmol) and malononitrile (1 mmol). First, the model reaction was performed without catalyst and solvent in two different temperatures, the yield of products was trace ( Table 2, entries 1 and 2). By adding the guanidinylated SBA-15/Fe 3 O 4 catalyst to the model reaction in the absence of solvent, the yield of the reaction was reached about 47% ( Table 2, entry 3). In the next step, to assess the solvent effect, ethanol was added to the reaction in the presence of a catalyst at room temperature, the efficiency increased considerably ( Table 2, entry 4). Then, the reaction was repeated at 80° C to evaluate the effect of temperature and observed that increasing the temperature up to 80° C leads to the reaction progress ( To assess the generality of the optimum conditions, a wide range of benzaldehydes bearing both electrondonating and electron-withdrawing substitution were tested. As is observed in Table 3, a wide range of substituted dihydropyrano [2,3-c]pyrazole derivatives were obtained in high yields by using guanidinylated SBA-15/Fe 3 O 4 mesoporous nanocatalyst in short reaction times.  [2,3-c], its catalytic activity in the synthesis of 5e derivatives was compared with some other previously reported methods. As indicated in Table 4, the present method is superior to the other methods in terms of the yields of products or the reaction condition.  21,28,55 . The reusability of prepared mesoporous catalysts in the synthesis of pyranopyrazoles derivatives was evaluated in several runs. For this, after completion of the reaction, the catalyst was separated from the reaction mixture by a magnet, eluted by ethanol and dried in an oven at 60 °C for 6 h in order to be ready for the next catalytic run. Later, the recovered catalyst in a constant amount was used for the subsequent runs. The presented results in Fig. 11 revealed that the recycled catalyst could be effective at least six consecutive runs without considerable reduction in its catalytic activity.