Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives

Abstract In this study, Fe3O4@urea/HITh-SO3H MNPs as a new, efficient, and recyclable solid acid magnetic nanocatalyst was synthesized and characterized using various methods including Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, energy-dispersive X-ray spectroscopy, and X-ray powder diffraction. After the characterization of this new magnetic nanocatalyst, it was efficiently utilized for the promotion of the one-pot synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives via three-component reaction of the 1,3-indanedione, aldehyde, and 1-naphthylamine/1,3-dimethyl-6-aminouracil under solvent-free conditions at 80°C. The procedure gave the desired heterocyclic structures in high-to-excellent yields and short reaction times. Also because of the magnetic nature of the nanocatalyst, it can be separated with an external magnetic field and reused at least six runs without any considerable decrease in the catalytic behavior.


Introduction
The use of magnetic nanoparticles (Fe 3 O 4 MNPs) as a core to support the catalyst in organic transformation has become quite popular in chemistry. Because they include unique features such as high dispersion and reactivity, easy separation under external permanent magnetic fields and reusability, pairing with two or multidentate ligands or inorganic structures [1][2][3][4][5][6]. The use of magnetic nanoparticles may be restricted for reasons such as deformation and aggregation during the chemical process [7]. To remove this restriction and reclaim their features for the specific application, these particles need to be modified by functionalizing their surface via organic or inorganic groups.

General
The chemicals used in this work were obtained from Merck, Fluka, and Aldrich chemical companies and were utilized with any further purification. All melting points were achieved on an Electrothermal 9100 instrument. Fourier transform infrared spectroscopy (FTIR) spectroscopy was done as KBr discs with a Shimadzu spectrometer. Thermogravimetric analysis (TGA) spectra were recorded using a TGA thermoanalyzer (PerkinElmer) instrument. Scanning electron microscopy (SEM) images were obtained using a Tescanvega II XMU Digital Scanning Microscope. Vibrating sample magnetometry (VSM) analyses were performed in a Lakeshore 7407 at ambient temperature. Energy dispersive X-ray spectroscopy (EDX) measurement was performed using ESEM, Philips, and XL30. X-ray powder diffraction (XRD) patterns of samples were obtained using a Siemens D-5000 X-ray diffractometer. Transmission electron microscope (TEM) images were recorded with a TEM Philips EM 208S instrument.

Preparation of Fe 3 O 4 @urea/HITh MNPs
Two grams of Fe 3 O 4 @CPTES/urea MNPs was dispersed in 25 ml dry toluene by ultrasonication for half an hour. Subsequently, 0.65 g of 4,5-dihydroxyimidazolidine-2thione (HITh) and 0.1 ml of trifluoroacetic acid (TFA) were added into the reaction flask, and the mixture was agitated for 1 h at ambient temperature. Then, the resulting solid product was separated by magnetic decantation, washed twice with distilled water (20 ml) and acetone (10 ml) to eliminate the unreacted chemicals, and dried in vacuum at 70°C for 18 h.

Preparation of Fe 3 O 4 @urea/HITh-SO 3 H MNPs
At the end of work, 1 g of Fe 3 O 4 @urea/HPITh MNPs was dispersed in 25 ml dry dichloromethane by ultrasonication for 30 min and then 10 mmol of 1,4-butane sulfonate was added to the reaction vessel. The reaction mixture was refluxed for 8 h; after this, the resulting solid product was isolated using magnetic decantation. The obtained solid catalyst was rinsed three times with 30 ml of distilled water and dried overnight in vacuum oven at 60°C. This synthesis is exhibited in Scheme 1. To ensure the completion of the reaction, thin layer chromatography (TLC) was used to monitor the reaction mixture. After viewing a single spot on the TLC for the final product, the catalyst was isolated using an external magnet, and the desired pure products were attained from the reaction container by recrystallization from the hot ethanol.

General process for the preparation of indeno [2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives 6
A mixture containing 1,3-indanedione (1 mmol), aldehyde (1 mmol), 1,3-dimethyl-6-aminouracil (1 mmol), and Fe 3 O 4 @urea/HITh-SO 3 H MNPs magnetic nanocatalyst (15 mg) reacted with each other in a one-pot condensation at 80°C under solvent-free conditions. To ensure the completion of the reaction, the reaction mixture was monitored using TLC. After viewing a single spot on the TLC for the desired product, the catalyst was separated by a permanent magnetic field, and the desired pure products were achieved from the reaction container by recrystallization from the hot ethanol.
Ethical approval: The conducted research is not related to human or animal use.      Figure 4. According to this image, the particle size of the synthesized heterogeneous magnetic nanocatalyst is found to be approximately 17 nm.

VSM analysis of Fe 3 O 4 @urea/HITh-SO 3 H MNPs
To study the magnetic feature of Fe 3 O 4 MNPs and Fe 3 O 4 @urea/HITh-SO 3 H MNPs, magnetic measurements were carried out by a room temperature VSM under applied magnetic field ( Figure 5). The obtained values  These values indicate that the magnetic saturation of the catalyst has been reduced. Despite this decline in the magnetic saturation, the heterogeneous magnetic nanocatalyst can still be efficiently isolated from the reaction mixture using a powerful magnet.

EDX analysis of Fe 3 O 4 @urea/HITh-SO 3 H MNPs
The elemental composition of Fe 3 O 4 @urea/HITh-SO 3 H MNPs was obtained using EDX ( Figure 6). The EDX spectrum exhibits the characteristic peaks (Fe, O, N, Si, and S) of the catalyst.

XRD analysis of Fe 3 O 4 @urea/HITh-SO 3 H MNPs
The structure of        1, entry 6). Moreover, when the reaction was conducted in the absence of a catalyst, the product yields decreased remarkably and only a trace level of the desired product was found on TLC, even after the reaction time was prolonged to 60 min ( Table 1,  entry 4). Also, the effect of temperature was checked on the reaction yield ( Table 1, entries 3 and 7-12). It is clear that a low yield of the product was achieved without heating (Table 1, entry 7). The yield of the product was increased at higher temperatures (entries 3 and 8-10). However, a further increase in temperature did not improve the yield of reaction ( Table 1, entries 11 and 12). After optimizing the reaction conditions, the generality of these conditions was studied via multifarious aromatic aldehydes, the outcomes of which are listed in Table 2. It was observed that aromatic aldehydes carrying both different electron-donating and electron-withdrawing groups were subjected to the condensation and in all cases, the relating 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one derivatives (4a-p) were obtained in high-to-excellent yields after the appropriate reaction times.      Also, we reported a fast and effective one-pot threecomponent production of indeno[2′,1′:5,6]pyrido [2,3-d] pyrimidine derivatives through the reaction of 1,3indanedione, aldehyde, 1,3-dimethyl-6-aminouracil in the existence of Fe 3 O 4 @urea/HITh-SO 3 H MNPs ( Table 3). To determine the best optimal conditions, we performed the reaction between 1,3-indanedione 1 (1 mmol), 4-nitrobenzaldehyde 2j (1 mmol), and 1,3-dimethyl-6aminouracil 5 (1 mmol), in the existence of 15 mg of Fe 3 O 4 @urea/HITh-SO 3 H MNPs at 80°C under solventfree conditions. The final product 6j was achieved with an excellent yield (96%) within 15 min ( Table 3, entry 3).
Under optimum conditions, the scope and generality of this procedure were explored. To synthesize indeno [2′,1′:5,6]pyrido [2,3-d]pyrimidine derivatives, a variety of aromatic aldehydes comprising electron-withdrawing and electron-donating groups in the existence of 15 mg of Fe 3 O 4 @urea/HITh-SO 3 H MNPs were investigated to react with 1,3-indanedione and 1,3-dimethyl-6-aminouracil, and the outcomes are listed in Table 4. It was observed that the above-mentioned aromatic aldehydes produced a high percentage of products in reaction with two other components. Scheme 3 presents a reasonable pathway for the one-pot three-component condensation of 1,3-indanedione 1, various aldehyde 2, 1-naphthylamine 3/1,3dimethyl-6-aminouracil 5, and Fe 3 O 4 @urea/HITh-SO 3 H MNPs. Initially, 1,3-indanedione 1 and carbonyl group of activated aldehyde 2 as the reactant materials react with each other through a Knoevenagel condensation Recyclability is an important merit of any catalysts, therefore, studying the recyclability of the Fe 3 O 4 @urea/ HITh-SO 3 H MNPs was necessary (Figure 8). To this end, the reaction was performed using the three-component condensation of 1,3-indanedione (1 mmol), 4-chlorobenzaldehyde (1 mmol), and 1-naphthylamine/1,3-dimethyl-6-aminouracil (1 mmol) in the existence of the catalytic  level of Fe 3 O 4 @urea/HITh-SO 3 H MNPs at 80°C. At the end of the reaction, the catalyst was isolated from the reaction solution using an external magnet and rinsed with ethanol several times, dried under reduced pressure, and reused in subsequent reactions at least 6 runs without any considerable reduction in the yield of the products.

Conclusion
In conclusion, a convenient and effective technique has been designed to synthesize 7-aryl-8H-benzo[h]indeno [1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido [2,3-d] pyrimidine derivatives through a one-pot three-component condensation of 1,3-indanedione, aldehyde, and 1-naphthylamine/1,3-dimethyl-6-aminouracil, respectively, using Fe 3 O 4 @urea/HITh-SO 3 H MNPs as a novel heterogeneous magnetic nanocatalyst under solvent-free conditions. Applying an efficient and eco-friendly catalyst, lower loading of the catalyst, magnetical recyclability of the catalyst, omitting organic solvent, simple operation, and high yields of the final products are some benefits of the described protocol. This nanocatalyst was isolated via a permanent magnetic field and recovered efficiently for the six runs without any significant reduction in the catalytic behavior.