One-Pot Access to Diverse Functionalized Pyran Annulated Heterocyclic Systems Using SCMNPs@BPy-SO3H as a Novel Magnetic Nanocatalyst

The SCMNPs@BPy-SO3H catalyst was prepared and characterized using Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Vibrating Sample Magnetometry (VSM), Energy Dispersive X-ray Spectroscopy (EDX), X-ray Diffraction (XRD), and Scanning Electron Microscopy (SEM). Afterwards, its capability was efficiently used to promote the one-pot, three-component synthesis of pyrano[2,3-c]pyrazole and 2-amino-3-cyano-pyrano[3,2-c]chromen-5(4H)-one derivatives. The strategy resulted in the desired products with excellent yields and short reaction times. The SCMNPs@BPy-SO3H catalyst was readily recovered using a permanent magnetic field and it was reused in six runs with a slight decrease in catalytic activity. Copyright © 2020 BCREC Group. All rights reserved


Experimental
All the pure chemical substances were purchased from Merck and Aldrich Companies and applied without any further purification. Melting points of the substrate were carried out on Electrothermal-9100 apparatus and uncorrected. Fourier transform infrared spectroscopy (FT-IR) was recorded with a PerkinElmer PXI spectrometer using the KBr wafers that was operating in the range of 400-4000 cm -1 . X-ray diffraction (XRD) patterns of samples was taken with a Philips instrument with a wavelength of 1.54 Å using Cu-K radiation. Thermogravimetric analyses (TGA) were examined by a Du Pont 2000 thermal analysis apparatus under nitrogen atmosphere at a heating rate of 10 °C/min. The magnetic properties were measured by a vibrating sample magnetometry (VSM; Lakeshore 7200 at 300 kVsm) at room temperature. Energy-dispersive X-ray spectroscopy (EDX) analysis was performed for the chemical composition of synthesized nanoparticles (ESEM, Philips, and XL30). Scanning electron microscope (SEM) images were recorded with an SEM-LEO 1430VP instrument about the size, shape and morphology of the nanoparticles.

Preparing Fe3O4 nanoparticles
In a typical method, a solution of FeCl2.4H2O (4.27 g) and FeCl3.6H2O (11.65 g) salts was dissolved in 150 mL deionized water and stirred under nitrogen atmosphere at 70 °C. Then, 15 mL NH4OH (25%) was slowly dropped into the reaction solution, while being sonicated under nitrogen atmosphere within 30 min. The color of the reaction mixture changed from orange to black. The product of magnetic nanoparticles was isolated magnetically from the reaction solution followed by rinsing several times with deionized water and vacuumdrying.

Preparing nano-Fe3O4@SiO2 core shells
The 1 g of Fe3O4 nanoparticles, 65 mL of ethanol and 25 mL of deionized water were added into 250 mL three-neck flask. The reaction solution was sonicated for 20 min. Then, 4 mL of NH4OH (25%) and 0.5 mL of tetraethylorthosilicate (TEOS) were added dropwise to the flask. The reaction mixture was stirred at ambient temperature for 16 h. Finally, the precipitate was isolated with an external magnetic field, rinsed with distilled water and ethanol, and then dried in a vacuum oven.

Preparation of Fe3O4@SiO2-PC magnetic nanoparticles
2 g of Fe3O4@SiO2 NPs was dispersed in 50 mL of dry toluene in a round-bottom flask using an ultrasonic water for 30 min. Afterwards, 4 mL of 3-chloropropyltriethoxysilane (PC) was slowly added into the flask and refluxed with mechanical stirring for 24 h under nitrogen gas protection. Afterward, the amino-modified magnetite nanoparticles were gathered using an external magnetic field followed by rinsing several times with ethanol and then being dried under vacuum oven.

Preparation of SCMNPs@ThSCa
1 g of the prepared Fe3O4@SiO2-PC magnetic nanoparticles was dispersed in 75 mL of ethanol using an ultrasonic bath for 30 min and mixed with 5 mL of thiosemicarbazide (ThSCa), and the reaction solution was refluxed for 24 h under a continuous flow of nitrogen gas. The resultant solid precipitates were isolated using a permanent magnetic field that was washed three times with distilled water to eliminate the unreacted chemicals and then dried in a vacuum oven for 17 h.

Preparing SCMNPs@ThSCa-BPy
1 g of the prepared SCMNPs@ThSCa was dispersed in 75 mL of ethanol and mixed with 2.2 mL of 2,2´-bipyridyl ketone (BPy). The reaction solution was stirred under reflux conditions for 12 h and the resultant solid product was separated using an external magnetic field that was rinsed several times to remove the unreacted chemicals; it was then dried in a vacuum.

Preparation of SCMNPs@BPy-SO3H
1 g of SCMNPs@ThSCa-BPy was added to 20 mL of dry dichloromethane and ultrasonically dispersed for 30 min. Afterwards, 6 mmol of chlorosulfonic acid was slowly added to the reaction vessel and the achieved mixture was stirred in the ice bath for 6 h. Finally, these precipitates were isolated from the reaction solution with a permanent magnet, washed several times with distilled water, and dried in a vacuum oven at 50 ℃ for 15 h. All stages of the SCMNPs@BPy-SO3H synthesis is shown in Scheme 1.
2.2.7 General process for the synthesis of pyrano[2,3-c]pyrazoles (5) A mixture of hydrazine hydrate (1 mmol), acetoacetic ester (1 mmol), aldehyde (1 mmol), malononitrile (1 mmol) and SCMNPs@BPy-SO3H (20 mg) was stirred at 80 °C under solvent-free conditions for the appropriate time. After completion of the reaction, the catalyst was removed using an external magnetic field and the achieved product was purified by recrystallization in aqueous ethanol.

FTIR Analysis of SCMNPs@BPy-SO3H
The FT-IR spectrum of the prepared Fe3O4, Fe3 O 4 @ S i O 2 , F e 3 O 4 @ S i O 2 -P C , SCMNPs@ThSCa, SCMNPs@ThSCa-BPy, and SCMNPs@BPy-SO3H is shown in Figure 1. In the spectrum of Fe3O4, the characteristic bands of the stretching vibration of the Fe-O-Fe and O-H were found at 575 cm -1 and 3386 cm -1 , respectively. The FT-IR spectrum of the Fe3O4@SiO2 showed associated absorption bands at 968 and 1065 cm -1 due to Si-O-Si and Si-OH stretching vibrations, respectively. The FT-IR spectrum of the Fe3O4@SiO2-PC exhibits a peak at 2978 cm -1 that is indexed to the C-H stretching vibration mode. The C=S and N-H stretching vibrations of the SCMNPs@ThSCa could be observed at around 2334 cm -1 and 3312 cm -1 , respectively. Additionally, the FT-IR spectrum shows a strong band at 1456 and 1638 cm −1 due to the C=C and C=N stretching vibrations, respectively, revealing the functionalization of the magnetic cores with organic groups. In the case of SCMNPs@BPy-SO3H, the bands at 1033 and 1142 cm -1 can be attributed to SO3H stretching vibration mode.

Thermal Analysis of SCMNPs@BPy-SO3H.
Thermogravimetric analysis spectrum of Fe3O 4 , Fe 3 O 4 @S iO 2 , Fe 3 O 4 @S iO 2 -P C, SCMNPs@ThSCa, SCMNPs@ThSCa-BPy and SCMNPs@BPy-SO3H was surveyed using TGA under nitrogen atmosphere at 10 ℃/min of heating rate. The results are shown in Figure  2. In the TGA graph of all of the samples, a weight loss of about 3% observed that is related to desorption of physically adsorbed water and dehydration of the surface hydroxyl groups.
an d SCMNPs@ThSCa undergoes other weight loss stages, which can be seen in the range between 330-460 °C, probably related to the elimination of attached 3-chloropropyltriethoxysilane (PC) and thiosemicarbazide (ThSCa) molecules. The TGA curves of SCMNPs@ThSCa-BPy and SCMNPs@BPy-SO3H show distinct stages of weight loss at temperatures within the range of 330-450 ℃, possibly attributed to the decompo-sition of attached functional groups to the Fe3O4 surface.

VSM Analysis of SCMNPs@BPy-SO3H
To study the magnetic properties of the Fe3O4, Fe3O4@SiO2, SCMNPs@ThSCa, and SCMNPs@BPy-SO3H, magnetic measurements were done at room temperature by a vibrating sample magnetometer (VSM). As shown in VSM patterns (Figure 3), the saturation magnetization (Ms) of the Fe3O4 is 64.79 emu.g -1 , which is higher than Fe3O4@SiO2 (52.34 emu.g -1 ) and SCMNPs@ThSCa (48.65 emu.g -1 ). This significant decrease in the Ms confirms the formation of the silica shell around the MNPs and organic groups on the surface of the SCMNPs. However, the saturation magnetization of SCMNPs@BPy-SO3H was 37.68 emu.g -1 , which is lower than that of SCMNPs. This additional decrease in the value of Ms is due to the formation of organic and SO3H groups on the surface of the Fe3O4.

EDX Analysis of SCMNPs@BPy-SO3H
The presence of functionalized groups on the surface of magnetic nanoparticles was also confirmed by the energy-dispersive X-ray spectroscopy (EDX) spectra showing the presence of Fe, C, N, S, Si, and O elements in the

SEM Analysis of SCMNPs@BPy-SO3H
The size and morphology of the Fe3O4 (A) and SCMNPs@BPy-SO3H (B) were investigated to determine the variations in the surface of the magnetic nanoparticles by the scanning electron microscopy (SEM) analysis. As shown in Figure 6, prepared magnetic nanoparticles in all the samples have nearly a spherical structure indicating the nanoparticles with a large surface area. In this research, we reported our outcomes for the efficient and rapid preparation of pyrano[2,3-c]pyrazole and 2amino-3-cyano-pyrano[3,2-c]chromen-5(4H)one derivatives using SCMNPs@BPy-SO3H as an efficient and reusable heterogeneous magnetic nanocatalyst under solvent-free conditions (Scheme 2).
Firstly, the catalytic efficiency of the SCMNPs@BPy-SO3H was studied in the synthesis of pyrano[2,3-c]pyrazole derivatives. To discover the appropriate reaction conditions, a one-pot four-component condensation of hydrazine hydrate (1 mmol), acetoacetic ester (1 mmol), 4-chlorobenzaldehyde (1 mmol), and malononitrile (1 mmol) was selected and tested as a model reaction under different conditions. We used various solvents, such as: H2O, EtOH, MeOH, CHCl3, CH3CN, CH2Cl2, and acetone under reflux conditions ( Table 1, entries 1-7). These observations illustrated that the reaction performed in the absence of solvent serves as the best result according to the principles of green chemistry for this synthesis (Table 1, entry 12). Although, EtOH with respect to having a polarity compared to other nonpolar solvents used in this reaction gave a moderate yield of the product (Table 1, [20][21][22][23][24]. In order to establish the efficiency of the optimum conditions (Table 1, Entry 12) in previously reported reactions, we surveyed the generality of this procedure with both electronwithdrawing and electron-donating aldehydes and the results are depicted in Table 2. All the investigated aldehydes afforded corresponding products in excellent yields and short reaction times.
Next   Table 3. To investigate the effect of various solvents, such as: H2O, EtOH, MeOH, CHCl3, CH3CN, CH2Cl2, acetone, and solvent-free conditions (Table 3, entries 1-8), the model reaction was done in the presence of these solvents and the best outcome was achieved in the absence of solvent (Table 3, entry 8). To illustrate the importance of temperature in the model reaction, the reaction was performed under different temperatures ranging from 25 to 100 °C (Table 3, entries 8 and 9-14). The yields of the desired product were increased and the reaction times were decreased with increased temperature up to 80 °C (Table  3, entries 8 and 9-12). In addition, the results show that the use of 90 and 100 °C led to slight decreases compared to 80 °C in terms of the product yields (Table 3, entries 13-14). To discover the best amounts of catalyst on the model reaction, organic transformation was done in the presence of 5, 8, 12, 15, 20, and 25 mg of SCMNPs@BPy-SO3H (Table 3, entries 8 and 15-20) and the highest yield of the product was achieved in the presence of 15 mg of catalyst (     [21][22][23][24][25]. After optimization of the reaction conditions for the model reaction, various 2-amino-3cyano-pyrano[3,2-c]chromen-5(4H)-ones were prepared with an array of aromatic aldehydes bearing either electron-withdrawing or electron-donating substituents by this procedure (Table 4).
The plausible mechanism for the synthesis of pyrano [2,3-c]pyrazole and pyrano[3,2c]chromen derivatives is shown in Scheme 3. In both cases, benzylidenemalononitrile 8 was achieved because of a Knoevenagel condensation between activated carbonyl group of aldehyde 3 by the SCMNPs@BPy-SO3H nanocatalyst and malononitrile 4. In the case of pyrano[2,3-c]pyrazole derivatives, hydrazine hy-drate 1 reacted with activated carbonyl group of acetoacetic ester 2 by the catalyst to form pyrazolone 9 via condensation reaction. After that, activated benzylidenemalononitrile 8 by the catalyst condense with 4-hydroxycoumarin 6 and pyrazolone 9 through Michael addition. The obtained 10 and 11 intermediates from these additions undergo cyclization and tautomerization (12 and 13) to develop the desired products 5 and 7.