Design, Characterization, and Application of The SCMNPs@PC/VB1-Zn as A Green and Recyclable Biocatalyst for Synthesis of Pyrano[2,3-c]pyrazole and 4H-benzo-[b]-pyran Derivatives

Eco-friendly and reusable solid acid catalysts (SCMNPs@PC/VB1-Zn) were identified as one of the most effective basic catalysts for the composition of a pot, three-component pyrano[2,3-c]pyrazoles. Methyl-1phenyl-1H-pyrazole-5(4H)-one, benzaldehyde and malononitrile in high yield at 80 °C. SCMNPs@ PC/VB1-Zn reports the simple and efficient catalysis of a three-component pot reaction of dimedone, aldehydes, and malononitrile to 4H-benzo-[b]-pyran derivatives. This magnetic nanocatalyst can be recycled more than 6 times without dramatically reducing performance with respect to reaction time and efficiency. Copyright © 2020 BCREC Group. All rights reserved


Introduction
Iron oxide magnetic nanoparticles, especially magnetite (Fe3O4) as the most extensive investigated magnetic nanoparticles (MNPs), exhibit unique physical and chemical features compared to the bulk materials and their use is expanding quite rapidly. Various strategies have been used to prepare Fe3O4 core-shell nanocomposites including coprecipitation [1], thermal decomposition [2], ultrasound irradiation, microemulsion, and hydrothermal synthesis [3] of which thermal decomposition and coprecipitation are the most commonly used procedures. Fe3O4 MNPs are particularly promi-tivities, including the inhibitors of human Chk1 kinase [22], antimicrobial [23], antiinflammatory [24], and anticancer [25] activities. In one of the important ways, pyrano [2,3c]pyrazole derivatives were synthesized by the three-component condensation reaction of pyrazolone, malononitrile, and aldehyde in the presence of various catalysts, such as: KF.2H2O [26], BF3/MNPs [27], p-dodecylbenzene sulfonic acid (DBSA) [28], H14[NaP5W30O110] [29], triethylbenzylammonium chloride (TEBA) [30], MgO [31], and hexadecyltrimethylammonium bromide (HTMAB) [32]. Most of the procedures reported for the preparation of these kind of heterocyclic compounds are associated with demerits such as long reaction time, low yields, the use of hazardous organic solvents, lack of general applicability, tedious work-up methods, use of toxic catalysts, and harsh reaction conditions. Therefore, the introduction of new and efficient strategy for the synthesis of pyrano [2,3-c]pyrazole derivatives can be useful.
In this study, we reported our outcomes for the rapid and efficient preparation of pyrano [2,3-c]pyrazoles and 4H-benzo-[b]-pyran derivatives using SCMNPs@PC/VB1-Zn as a green and recyclable heterogeneous magnetic biocatalyst under solvent-free conditions (Scheme 1).

Experimental
FT-IR spectra were collected with a Perki-nElmer PXI spectrometer in the range 400-4000 cm -1 on KBr pellets. The X-ray diffraction patterns of samples were obtained in the 2θ range of 10-80° at room temperature on a Philips X-pert diffractometer (Holland) with Co-K ( = 1.54 Å). Scanning electron microphotograph (SEM) was utilized to survey the catalyst morphology on an LEO 1430VP instrument. Thermal gravimetric analysis was performed using a Linseis STA PT 1000 instrument with a heating rate of 10 ℃/min over a temperature range of 25-700 °C under N2 atmosphere. The magnetic susceptibility measurements of the catalyst were obtained using a vibrating sample magnetometry (VSM; Lake Shore 7200 at 300 kVsm).

Preparation of the Fe3O4 magnetic nanoparticles (Fe3O4 MNPs)
First, a mixture of 4.8 g FeCl3.6H2O and 2.4 g FeCl2.4H2O was added to 100 mL of deionized water and the contents of the reaction vessel were vigorously stirred under the argon atmosphere at 80 °C for 20 min. Then, 10 mL of concentrated solution of ammonia was added quickly to the reaction solution and stirred again for 30 min. To achieve the desired precursor, the reaction solution was cooled and the formed black magnetic nanoparticles were isolated by the magnetic decantation. The desired precipitates were consecutively washed with deionized water and dried overnight in the absence of temperature under vacuum.

Preparation of the silica-coated magnetic nanoparticles (SCMNPs)
First, the achieved black magnetic nanoparticles from the first step was dispersed in a mixture of ethanol (80 mL), deionized water (25 mL) and concentrated aqueous ammonia (8 mL) and was sonicated for 30 min. Under continuous mechanical stirring, 20 mL of tetraethylorthosilicate (TEOS) was added to the reaction solution and was stirred for 24 h. The obtained Fe3O4@SiO2 precipitate was separated by magnetic decantation and consecutively washed with deionized water and ethanol and dried under vacuum at 50 ℃ for 10 h.

Preparation of the silica-coated magnetic nanoparticles bonded 3chloropropyltriethoxysilane (SCMNPs@PC)
The 4 mL of 3-chloropropyltriethoxysilane (CPTCSi) was added to the reaction vessel containing 2 g of dispersed SC@Fe3O4 MNPs in 50 mL dry toluene and stirred at 60 ℃ for 24 h. The residue solid (SCMNPs@PC) was separated via the magnetic decantation, consecutively washed with ethanol to remove the excess CPTCSi, and dried in a vacuum oven at 60 ℃ for 12 h.

Preparation of the SCMNPs@PC/VB1
The 2 g of SCMNPs@PC was added to the reaction vessel containing 50 mL of ethanol and dispersed for 30 min. Then, 1 mmol of thiamine hydrochloride (VB1) and 3-4 drop of triethylamine were added to the reaction mixture and refluxed for 12 h. The solid residue was extracted by an appropriate magnetic field, consecutively washed with ethanol, and dried under the vacuum oven.

Preparation of SCMNPs@PC/VB1-Zn.
The 2 g of the prepared SCMNPs@PC/VB1 was dispersed in 50 mL of acetonitrile for 30 min. Then, 0.1 g of Zn(OAc)2 was poured to the reaction solution. After that, the contents of the reaction vessel were refluxed for 24 h and the resulting nanoparticles were isolated using an external magnetic field. The solid residue was washed several times with dry ethanol and dried at 70 °C for 24 h. All stages of the SCMNPs@PC/VB1-Zn synthesis are shown in Scheme 2.
A mixture of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (1 mmol), aldehyde (1.1 mmol), m a l o n o n i t r i l e ( 1 . 1 m m o l ) , a n d SCMNPs@PC/VB1-Zn (10 mg) was stirred at 80 °C in the absence of any solvents for the appropriate time. The progress of the reaction was monitored by thin layer chromatography (TLC). In order to extraction of the catalyst, ethanol was added to the reaction vessel and stirred at 70 °C. After complete dissolution of the product in the desired solvent, the catalyst was isolated from reaction solution by an external magnetic field and rinsed several times with ethanol. The obtained products were crystallized from ethanol to give pure products.

Typical procedure for the preparation of pyrano[2,3-c]pyrazole derivatives.
A mixture of dimedone (1 mmol), aldehyde (1 mmol), malononitrile (1.2 mmol), and SCMNPs@PC/VB1-Zn (10 mg) was stirred at 50 °C in the absence of any solvents for the appropriate time. After completion of the reaction, as it can be seen from thin layer chromatography (TLC), ethanol was added to the reaction vessel and stirred at 70 °C. After complete dissolution of the product in the desired solvent, the catalyst was isolated from reaction mixture by an external magnetic field and rinsed several times with ethanol. After evaporation of ethanol, the achieved products were washed with nhexane to give appropriate compound in pure form. Figure 1 shows the FT-IR spectra of Fe3O4 M N P s , S C M N P s , S C M N P s @ P C , SCMNPs@PC/VB1, and SCMNPs@PC/VB1-Zn. As is clear from all of the spectra, the broad absorption of 3408 cm -1 belongs to the O-H stretching vibrations. In the spectrum of Fe3O4 MNPs, the characteristic absorption at 585 and 456 cm -1 are associated to Fe-O-Fe stretching vibrations related to the magnetite phase. As can be seen from the FT-IR spectrum of the SCMNPs, the introduction of a layer of SiO2 to Scheme 2. Preparation of SCMNPs@PC/VB1-Zn core-shell catalyst. the surface of MNPs can be verified by band at 1103 cm -1 which is assigned to the stretching vibration of Si-O-Si group. After bonding the SCMNPs with 3-chloropropyltriethoxysilane (CPTCSi), the FT-IR spectrum of the SCMNPs@PC exhibits a new peak at 2985 cm -1 assigned to the C-H stretching vibration of the aliphatic group. The bands at 1533 and 1640 cm -1 are attributable to the C-N and N-H (NH2) vibrations of the VB1 group indicate that the SCMNPs@PC are functionalized with thiamine. It should be noted that the C-N and N-H signal of the SCMNPs@PC/VB1-Zn are shifted to a lower wavenumber than the C-N and N-H signal of the SCMNPs@PC/VB1 (1529 and 1637 cm -1 rather than 1533 and 1640 cm -1 ).

TGA Analysis of SCMNPs@PC/VB1-Zn.
Using TGA, we investigated the thermal stability of the Fe3O4 MNPs, SCMNPs, SCMNPs@PC, SCMNPs@PC/VB 1 , and SCMNPs@PC/VB1-Zn were investigated. The outcomes of these analyses are exhibited in Figure 2. In the TGA curve of the all samples, the first small amount of weight loss in 100-150 °C is attributed to the both the physisorbed and chemisorbed solvents and hydroxyl groups on the surface of the magnetic nanoparticles. In the TGA curve of SCMNPs@PC, a weight loss below 350 °C is resulted from the decomposition of the coating organic layer of chloropropyl on the Fe3O4 MNPs surface. The weight loss of the SCMNPs@PC/VB1, and SCMNPs@PC/VB1-Zn at the temperature range of 150-450 °C are attributed to the decomposition of the organic parts of chloropropyl and thiamine on the surface of the magnetic phase.

EDX analysis of SCMNPs@PC/VB1-Zn
The results of the element distribution of SCMNPs@PC/VB1-Zn were further surveyed by EDX analysis (Figure 3). The coating of SiO2 on the Fe3O4 MNPs surface was verified by the presence of Si, Fe, and O signals. The existence of C, S, O, and N signals exhibits that the thiamine is loaded on the surface of SCMNPs@PC/VB1. The EDX analysis also presents the existence of the zinc element indicating coordination of Zn with thiamine. The appearance of the zinc element in the EDX analysis is attributed to SCMNPs@PC/VB1-Zn catalyst, indicating coordination of Zn with thiamine has been done successfully.

SEM Analysis of SCMNPs@PC/VB1-Zn
As shown in Figure 6, in order to determine the variations in the surface of the prepared magnetic nanoparticles, the morphology and size of the SCMNPs@PC/VB1-Zn (A) and recovered SCMNPs@PC/VB1-Zn (B) were studied by scanning electron microscopy (SEM). The SCMNPs@PC/VB1-Zn (A) exhibits a nearly spherical structure with an average particle diameter about 32 nm. As is clear from SEM images, the diameters of the recovered SCMNPs@PC/VB1-Zn (B) are about 38-46 nm with a negligible increase in the size.

TEM Analysis of SCMNPs@PC/VB1-Zn
The TEM image of the SCMNPs@PC/VB1-Zn exhibits that the dark Fe3O4 MNPs cores have an almost spherical shape with a narrow size distribution and surrounded by the grey silica shell (the average particle size is 50 nm, Figure 7). In the first study, the condensation of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (1 mmol), benzaldehyde (1.1 mmol), and malononitrile (1.1 mmol) for the synthesis of pyrano[2,3-c]pyrazoles was selected as a model reaction. The effects of amounts of SCMNPs@PC /VB1-Zn, reaction temperature, different sol-     [13][14]. In this reaction, the best results were achieved using 10 mg of catalyst (  Entries 15-19). The results showed that SCMNPs@PC/VB1-Zn is a more efficient catalyst than the reported ones in the literature with respect to the easy work-up, using a reusable catalyst, low catalyst loading, short reaction time and high yield.
To ascertain the scope and generality of the present system, various aromatic aldehydes   with both electron-withdrawing and electrondonating substituents were explored and the results of their reaction with 3-methyl-1phenyl-1H-pyrazol-5(4H)-one and malononitrile (or ethyl cyanoacetate) were summarized in Table 2. Aromatic aldehydes with both electronwithdrawing and electron-donating groups underwent smooth transformation to the corresponding pyrano [2,3-c]pyrazole derivatives, with no side products formation at high-toexcellent yields and in short reaction times.
The catalytic activity of SCMNPs@PC/VB1-Zn was investigated for the synthesis of 4Hbenzo-[b]-pyran derivatives via one-pot threecomponent reactions of dimedone, aldehydes, and malononitrile. To optimize the reaction conditions, we investigated the condensation among dimedone, 4-chlorobenzaldehyde, and malononitrile as a model reaction in the presence of various conditions (Table 3). In the best reaction condition, we used 10 mg of the SCMNPs@PC/VB1-Zn for 1 mmol of any substrates at 50 o C under solvent-free conditions ( Table 3, Entry 4). Moreover, in order to compare the efficiency of this prepared catalyst with that of some previously reported catalysts for the synthesis of 4H-benzo-[b]-pyran derivatives ( see Table 3, Entries 12-16), we bring the results for these catalysts in the synthesis of 6d as a model reaction.
After optimizing the conditions, the efficiency and versatility of the SCMNPs@PC/VB1-Zn as a catalyst for the preparation of 4H-benzo-[b]-pyran derivatives were evaluated by different aromatic aldehydes with both electronwithdrawing and electron-donating substituents. In all the studied cases, the reaction proceeded smoothly to give the desired products 6a-m (Table 4).

Conclusion
A simple method for the immobilization of Fe3O4 MNPs by functional groups was introduced via the reaction of OH groups on Fe3O4 level. Innovative SCMNPs@PC/VB1-Zn has been utilized as an effective and reusable catalyst for one-pot synthesis of pyrano [2,3c]pyrazoles and 1,8-dioxooctahydroxanthene derivatives. Serious analyses, such as: FTIR, XRD, VSM, EDX, TGA, and SEM, investigated the structure of the synthesized catalysts. The significant advantages of our protocol include high-to-excellent yields, short reaction time, simple separation and reusability of the catalyst.