Synthesis of Novel Azo-Linked 5-Amino-Pyrazole-4-Carbonitrile Derivatives Using Tannic Acid–Functionalized Silica-Coated Fe3O4 Nanoparticles as a Novel, Green, and Magnetically Separable Catalyst

Tannic acid–linked silica-coated Fe3O4 nanoparticles (Fe3O4@SiO2@Tannic acid) were prepared and characterized by transmission electron microscope (TEM), field emission scanning electron microscope (FE-SEM), X-ray powder diffraction (XRD), X-ray spectroscopy (EDX), vibrating sample magnetometry (VSM), and Fourier transform infrared (FT-IR) spectroscopy. Fe3O4@SiO2@Tannic acid supplies an environmentally friendly procedure for the synthesis of some novel 5-amino-pyrazole-4-carbonitriles through the three-component mechanochemical reactions of synthetized azo-linked aldehydes, malononitrile, and phenylhydrazine or p-tolylhydrazine. These compounds were produced in high yields and at short reaction times. The catalyst could be easily recovered and reused for six cycles with almost consistent activity. The structures of the synthesized 5-amino-pyrazole-4-carbonitrile compounds were confirmed by 1H NMR, 13C NMR, and FTIR spectra, and elemental analyses.


INTRODUCTION
One of the largest groups of heterocyclic compounds is five-membered rings with more than one heteroatom. One of the 5-membered rings with 2-heteroatom heterocycles is pyrazoles. Pyrazoles and their salts have numerous biological and pharmaceutical properties such as anti-inflammatory, sedative, hypnotic, fever-resistant, antifungal, and antibacterial. For example, 1) phenylbutazone acts as an anti-inflammatory agent, 2) diphenucate acts as a herbicide, 3) tartazine acts as a food coloring agent, 4) cecluxib acts as an anti-inflammatory agent, and 5) pyrazophine acts as a natural antibiotic and antitumor agent (Figure 1) (Bekhite and Aziem, 2004;Liu et al., 2008).
Some methods have also been reported for the synthesis of pyrazoles with azo bridges, such as the preparation of azo dyes from pyrazoles with a nitro group, such as 1-aryl-5-amino-4cyano-pyrazole as the starting material (Towne et al., 1968), and the coupling reaction between pyrazolo[3,4-d]-pyrazine with phenol and 1-naphthol (Kasimogullari et al., 2010).
Chemistry is advancing toward new approaches that focus on the environment. Chemists try to use green techniques such as nontoxic solvents (such as water), solvent-free syntheses, cheap and available catalysts, and one-step multicomponent reactions; nanocatalysts play an essential role in green synthesis. Nanodimensions provide tremendous advantages for using nanoparticles as catalysts. By reducing the particle size of the catalyst, there is an increase in contact surface with the reactants, and the catalytic power is improved, resulting in maximum efficiency with a small amount of catalyst. Another useful feature of nanocatalysts is their heterogeneity with high catalytic activity, so at the end of the reaction, the catalyst can be separated from the reaction mixture by smoothing and reused (Polshettiwar and Varma, 2010;Fihri et al., 2011;Fardood et al., 2017;Rezaei et al., 2017).
Compared to other nanoparticles, magnetite (Fe 3 O 4 ), due to its unique magnetic properties (Xin et al., 2020), easy magnetic separation (Hamedi et al., 2018), low toxicity (Zhao et al., 2014), environmental compatibility (Eslahi et al., 2021), and chemically modifiable surface (Bai et al., 2013), has attracted scientists. Therefore, applications of these magnetic nanoparticles (MNPs) have been developed in drug delivery, cancer treatment, magnetic resonance imaging, tissue repairing, contrast agents, magnetic storage media, biosensing, magnetic inks for jet printing, and catalysis (Inaloo et al., 2020;Eslahi et al., 2021). However, MNPs easily aggregate in aqueous solutions due to their anisotropic dipolar attraction (Sardarian et al., 2019). Also, they are unstable in acidic environments and may be oxidized by air, which can alter their magnetic properties, reduce adsorption capacity, and limit the range of application (Pourjavadi et al., 2012). To overcome this limitation, stabilization of MNPs is performed. Magnetic shells, with core advantages and a wide range of shells, have attracted much attention in intensive research (Zhao et al., 2015).

Material and Method
Chemicals were purchased from Merck and Fluca and used as raw materials of standard purity. Melting temperatures were measured on electro-thermal 9100 devices and were uncorrected. For ultrasound reactions, the ultrasound apparatus Astra 3D (9.5 dm 3 , 45 kHz, 305 W) from TECNO-GAZ was used. FT-IR spectra were obtained on a Shimadzu FT-IR-8400S spectrometer. A Bruker DRX-500 Avance spectrometer was used to obtain the 1 H NMR and 13 C NMR spectra with DMSO-d 6 as the solvent and TMS as internal standard. Elemental analyses were recorded on a Carlo-Erba EA1110CNNO-S analyzer. All mechanochemical reactions were carried out using a Retsch MM400 vibrational ball mill, equipped with Retsch 25 ml screw-top vessels, containing a 13.6-g stainless steel ball of 15 mm diameter unless otherwise stated. The operating frequency was set at 25 Hz for each experiment. The products were dried in a Carbolite PF60 oven set at 80°C. was confirmed by FT-IR, XRD, EDX, VSM, TEM, and SEM techniques (Figures 2-8).
The structure of the Fe 3 O 4 @SiO 2 @Tannic acid nanoparticles is synthesized in three steps from existing commercial materials, as shown in Figure 2. Fe 3 O 4 @SiO 2 core-shell structures were sequentially treated with 3-chloropropyltrimethoxysilane. Next, it was treated with tannic acid to produce Fe 3 O 4 @SiO 2 @Tannic acid ( Figure 2).
FT-IR spectroscopy of Fe 3 O 4 @SiO 2 @Tannic acid MNPs was performed to identify the functional groups of the synthesized nanoparticles. The strong stretching bond at 3,409 cm −1 is related to the O-H stretching vibrations of the phenolic moiety of the nano-catalyst, and C O stretching bands of carboxylic acid were shown at 1704 cm −1 , which confirms the presence of tannic acid in the structure of nanoparticles. The bonds at 1,620, 1,506, and 1,453 cm −1 are assigned to the C C stretching vibrations of the aromatic moiety. Also, vibrations of Si-O-Si bonds in the SiO 2 shell were observed at 1,116 and 906 cm −1 (Figure 3). The size and morphology of the Fe 3 O 4 @SiO 2 @Tannic acid MNPs were studied using transmission electron microscopy and field emission scanning electron microscopy (Figures 4, 5). The transmission electron microscope (TEM) and field emission scanning electron microscope (FE-SEM) images in Figures 4, 5 show that the Fe 3 O 4 @SiO 2 @Tannic acid nanoparticles have an almost spherical morphology with a particle size of 10-20 nm. In addition, TEM images show aggregation that confirms the successful bonding of tannic acid with magnetic nanoparticles (Figures 4, 5).
The data from the energy-dispersive X-ray spectroscopy (EDX) analysis of the synthesized Fe 3 O 4 @SiO 2 @Tannic acid MNPs confirm the nanoparticle structure. Thus, the presence of Fe (21.35 w/w %), O (52.38 w/w %), Si (0.36 w/w %), and C (25.92 w/w %) atoms in the structure proves the presence of Fe 3 O 4 core in the structure of Fe 3 O 4 @SiO 2 @Tannic acid MNPs ( Figure 6).
The VSM plot of the Fe 3 O 4 @SiO 2 @Tannic acid MNPs is presented in Figure 7. As can be seen, the saturation magnetization of the MNPs is smaller than that of the pure Fe 3 O 4 . VSM was measured during solid sampling at the tip of a vibrating rod at room temperature and analyzed in an applied magnetic field from −10 to 10 kOe (Figure 7).

Catalytic Application
To evaluate the catalytic capability of the synthesized heterogeneous catalyst (Fe 3 O 4 @SiO 2 @Tannic acid) in organic reactions, we chose to examine its activity in a one-pot mechanochemical reaction between synthetized azo-linked aldehydes, malononitrile, and phenylhydrazine or p-tolylhydrazine (Scheme 1).

Effect of Fe 3 O 4 @SiO 2 @Tannic Acid Catalyst Value
The synthesis of product 4a with different amounts of Fe 3 O 4 @ SiO 2 @Tannic acid at room temperature was investigated, and it was found that 0.1 g of the desired catalyst per 1 mmol of substrate gave a better yield in a shorter reaction time ( Table 2).
To present the efficiency and generality of the mechanochemical reaction, various azo-linked aldehydes, malononitrile, and phenylhydrazine or p-tolylhydrazine were reacted in the presence of Fe 3 O 4 @SiO 2 @Tannic acid at room temperature (Scheme 1 and Table 3).
The recyclability and reusability of a catalyst were studied in the model one-pot mechanochemical reaction between various azo-linked aldehydes, diverse hydrazines, and malononitrile. At the end of the reaction, the separated catalyst can be reused after washing with warm EtOH and drying at 80°C. Fe 3 O 4 @SiO 2 @Tannic acid was used again for subsequent experiments under similar reaction conditions. The catalyst could be reused for the next cycle without any considerable loss of its activity. The yields of the product decreased only slightly after reusing the catalyst six times ( Table 4). TEM images of the synthesized Fe 3 O 4 @SiO 2 @ Tannic acid MNPs after one cycle of reaction and after six cycles of reaction are shown in Figure 5.

CONCLUSION
In conclusion, Fe 3 O 4 @SiO 2 @Tannic acid was synthesized and investigated as a new, environmentally friendly, inexpensive, mild, and reusable catalyst for the mechanochemical synthesis of azo-linked 5-amino-pyrazole-4-carbonitriles. High yield, a simple work-up procedure, observance of green chemistry principles, eco-friendly procedure using natural ingredients, ease of separation, recyclability of the magnetic catalyst, and waste reduction are some advantages of this method.