Design of an efficient magnetic brush solid acid and its catalytic use in organic reactions

Abstract

In this research, with the Green Chemistry approach, to load more sulfonic acid active sites on catalyst surfaces, a nanocomposite material based on core-shell magnetite coated with vinyl silane and a sulfonated polymeric brush-like structure is designed and synthesized as a new class of efficient solid acid catalysts, referred to as Fe₃O₄@VS-APS brush solid acid. The synthesized catalyst was comprehensively characterized by a range of instrumental techniques, including XRD, SEM, TEM, FT-IR, EDX, TGA, and VSM. The activity of the catalyst was evaluated in Biginelli, Strecker, and esterification reactions. The Fe₃O₄@VS-APS brush solid acid has special features, such as easy reusability when a simple magnet is used for four reaction runs, an appropriate balance between hydrophobic and hydrophilic properties on the catalyst surface, and effective catalytic performance in the production of 3,4-dihydropyrimidin-2-one(thione) derivatives, 2-phenyl-2-(phenylamino)acetonitrile and octyl acetate.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-025-86027-6.

Introduction

Today green chemistry, a field that emphasizes environmentally friendly approaches, has gained significant attention in recent years. This includes the use of eco-friendly catalysts and solvent-free conditions for organic synthesis and reactions¹. The use of heterogeneous catalysts, particularly solid acids, has emerged as a key focus in this area¹. They can be easily separated from the reaction medium, eliminating the need for a neutralization process and reducing disposal issues. In other words, the most important advantages of heterogeneous catalysts over homogeneous catalysts include easier recovery by filtration from reaction mixtures, reusability for multiple uses, and excellent adaptability to continuous flow processes. This not only makes the process green and cost-effective but also maximizes atomic utilization^1,2. Therefore, the use of solid acids, is a significant step toward achieving the goals of green chemistry³.

In recent decades, extensive research has been conducted to modify the surfaces of various polymers for use in a variety of fields, which range from raw materials, engineering sciences, and biological sciences to catalytic chemical reactions⁴. Among many types of polymers, few studies have focused on hairy particles with brush-like structures^5–7. These polymers consist of a central core and numerous dense polymer chains surround the core of hairy particles with a brush-like structure. These chains are attached to the core through covalent bonds. The core can be made of various materials, such as minerals, metals, or organic compounds, and its size can vary from micro to nanometers^8,9. In addition to having a spherical shape, cores can have cylindrical or rod-shaped shapes^10,11. The brush layer can be made of different types of polymers: neutral or charged, flexible or rigid, and single- or multi-component systems. They can be designed to be used for specific purposes by combining the properties of the core particles and the polymer brush shell^12–14. In this research, to produce a robust solid acid catalyst, a grafted magnetic particles with a polymer brush shell was synthesized by attaching olefinic functional groups on the surface of the Fe₃O₄ MNPs core, and then brush-like polymer chains were grown via the polymerization process.

Among the polymerization processes that control radical polymerization methods, such as atom transfer radical polymerization (ATRP), nitroxide-mediated radical polymerization (NMRP), and reversible addition fragmentation chain-transfer polymerization (RAFT) have been used to make dense polymer brushes on many different substrates, ranging from quantum dots and carbon nanotubes to silica and gold nanoparticles^15–19. Surface-initiated ATRP is a powerful technique for introducing uniform polymer layers on solid surfaces^16,20–24. This polymerization method fulfills our goal of achieving high loading of catalyst active sites through brush-like polymer chains while allowing them to be properly accessible, making them an effective tool in the field of catalysis. In this regard, in a small number of studies, brush polymers with sulfonic acid active sites have been considered in the field of catalysis^25–28. They offer high efficiency, stability, and recyclability, which makes them ideal for green synthesis. Therefore, these brush polymer-based catalysts have been used in some organic reactions. Long and co-workers²⁵ synthesized a new type of sulfonic acid hybrid catalyst based on poly(styrene sulfonic acid) brush materials with a silica core. The synthesized catalyst was evaluated for the hydrolysis of ethyl lactate. This work emphasizes the need to understand the stability of acid catalysts in the presence of water and the importance of synthesizing new ‘water-tolerant’ acid catalysts. Riccardi and co-workers²⁶ synthesized a catalyst made of polymer brushes containing sulfonic acid active sites and immobilized it on the inner walls of continuous flow glass microreactors. The performance of the sulfonic acid catalyst located in the microreactor wall was evaluated in the hydrolysis of benzaldehyde dimethyl acetal. ِِDurie and co-workers²⁷ synthesized a catalyst derived from three distinct polymer brush systems: alkylsulfonyl fluorides, aromatic sulfonyl fluorides, and aromatic fluorosulfonates, which react with three different silyl ether derivatives. In another study, Wang and co-workers²⁸ synthesized a dual-functionalized block copolymer brush catalyst and used it for the direct esterification of methacrylic acid and methoxy polyethylene glycol for the synthesis of methoxy polyethylene glycol methyl acrylates.

Solid acids find widespread use in various organic chemistry reactions, and they also play a significant role in multicomponent reactions. In other words, multicomponent reactions (MCRs) have emerged as a crucial class of reactions, particularly when heterogeneous catalysts are used^29,30. MCRs involve the use of at least three reactants, and the majority of the starting components are integrated into the resulting structures. This approach is simple, has excellent selectivity, and efficiently reduces the time required for separation and purification. Strecker made the initial and significant contribution to the development of multicomponent reactions in 1850³¹. These reactions have facilitated the synthesis of a large number of compounds, holding the upper hand over multistep synthesis owing to their efficiency, cost-effectiveness, easy operation, high product complexity, and large molecular diversity. Therefore, the green approach of MCRs, especially when heterogeneous catalysts are used, has made them an essential part of modern synthetic chemistry^29–34.

One of the important multicomponent reactions is the Biginelli reaction. The Biginelli reaction is a three-component reaction that was first reported in 1893. The Biginelli reaction is a method for synthesizing 3,4-dihydropyrimidin-2-ones(thiones), which have diverse medicinal properties. The reaction involves the condensation of an aldehyde, a β-keto ester, and a urea or thiourea, typically catalyzed by strong liquid acids. Despite its original limitations, such as low yields with substituted and aliphatic aldehydes, severe conditions, and long reaction times, advancements have led to the use of heterogeneous catalysts, ionic liquids, and immobilized ionic liquids to improve the process. The products of the Biginelli reaction, 3,4-dihydropyrimidin-2-ones(thiones), are used in various pharmacological and therapeutic applications, including antitumor, antihypertensive, antithyroid, anti-HIV and anticancer treatments (Fig. 1)^35–37.

Fig. 1.

Illustrative pharmacologically active 3,4-dihydropyrimidin-2-ones(thiones).

With the rise of green technology and sustainable chemistry, the Biginelli reaction has been adapted to be more environmentally friendly, achieving improved yields and facilitating the efficient synthesis of bioactive compounds. This includes the use of various heterogeneous catalysts and different solvents to synthesize many Biginelli-type compounds^38,39. Some of these methods employ catalysts such as polystyrene sulfonic acid⁴⁰, polystyrene-poly(ethylene glycol) resin-supported sulfonic acid⁴¹, mesoporous silica MCM-41⁴², silica sulfuric acid⁴³, and sulfonated carbon materials⁴⁴.

Additionally, the construction of sulfonic acid sites immobilized on magnetite nanoparticles involves the use of facile and efficient methods. The synthesis of 3,4-dihydropyrimidinone(thione) derivatives utilizing sulfonated Fe₃O₄@SiO₂ core-shell magnetic nanoparticles as recyclable catalysts and eco-friendly materials has been investigated on the basis of the principles of green chemistry to develop an ideal synthesis approach^45–47. The Fe₃O₄ nanoparticles were prepared via a chemical co-precipitation method. Next, the magnetic core was coated with a siliceous shell via the Stober process. Magnetite nanoparticles have attracted much research interest in recent years because of their unique physicochemical properties and great potential for various biomedical applications^48–51. Owing to their functionalizable surfaces, magnetite nanoparticles are promising for creating heterogeneous catalysts^45–47. Despite the many advantages of magnetite nanoparticles, they easily aggregate and owing to their limited surface area the loading of catalytically active sites on them is low. To prevent aggregation and enhance their surface area and surface functionality, the grafting of hydrophilic/hydrophobic, biocompatible, and biodegradable components is a key research area^52–55. In other words, using a shell that increases the specific surface area and thus the loading of the catalytic active sites can produce a much more efficient catalyst. In this regard, core-shell particles, with magnetite cores and polymer shells, are highly regarded as a matrix for heterogeneous catalysts because of the synergistic effect of the magnetite nanoparticles (which are easy to separate with an external magnet) and the high potential of the polymer shell for surface functionalization^52–55. To the best of our knowledge, no heterogeneous catalyst with a magnetic core and brush polymer shell has been investigated in the three-component Biginelli reaction. Therefore, as part of our efforts to explore novel magnetic catalysts to catalyze various organic transformations herein, a magnetic brush sulfonic acid catalyst, Fe₃O₄@VS-APS, was synthesized and its utility and efficiency were investigated in Biginelli, Strecker and esterification reactions (Fig. 2).

Fig. 2.

Illustrative description of the Fe₃O₄@VS-APS brush solid acid.

Experimental

Chemicals and characterization methods

Chemicals such as 1-vinyltriethoxysilane (VS), benzoyl peroxide (BP), 2-acrylamido-2-methylpropane sulfonic acid (APS), ferric chloride hexahydrate (FeCl₃·6H₂O), ferrous chloride tetrahydrate (FeCl₂·4H₂O), ethyl acetate, n-hexane, toluene, ethanol, ammonium hydroxide, sodium hydroxide, sodium chloride, sulfuric acid, urea, thiourea, methylacetoacetate, and various aldehydes, were supplied commercially by Merck, Sigma-Aldrich, Tianjin Chemical Factory, and Dr. Mojallali Co. FT-IR spectra were analyzed via a Perkin-Elmer spectrometer within the 4000–400 cm^− 1 range, with materials provided as KBr tablets. The X-ray diffraction patterns were determined via a PHILIPS PW1730 XRD device. SAMX detected the energy-dispersive X-ray (EDX) analysis. A MIRA III - TESCAN device was used to conduct field emission scanning electron microscopy (FESEM).

TEM images were captured with a Philips EM 208 S microscope at an accelerating voltage of 100 kV. Vibrating sample magnetometer (VSM) analysis was performed via the MDKB model developed by Kashan Kavir Magnetism. The thermal stability of the supported catalysts was examined via a TA Q600 thermogravimetric analyzer (TGA) in the temperature range of 0–800 °C.

Preparation of magnetic samples

Synthesis of Fe₃O₄

The procedure described by Luo and co-workers⁵⁶ was employed for the synthesis of Fe₃O₄ MNPs. For the conventional preparation process, 11.0 g (40.7 mmol) of ferric chloride hexahydrate (FeCl₃·6H₂O) and 4.0 g (20.1 mmol) of ferrous chloride tetrahydrate (FeCl₂·4H₂O) were dissolved in 250 mL of deionized water at 85 °C. The dissolution took place under a nitrogen environment with the assistance of a mechanical stirrer. The pH of the solution was regulated to a range of 9–11 by introducing aqueous ammonia (25%). Following 4 h of continuous stirring, the magnetite precipitates were thoroughly washed with distilled water until the pH reached 7.0. The black Fe₃O₄ precipitate was retrieved from the bottom of the reaction flask via a permanent magnet. The Fe₃O₄ MNPs, which formed a dark precipitate, were subsequently rinsed with ethanol (3 × 15 mL) and desiccated under vacuum at room temperature overnight (Scheme 1a).

Scheme 1.

Synthesis pathways of (a) Fe₃O₄ MNPs, (b) Fe₃O₄@VS, and (c) Fe₃O₄@VS-APS brush solid acid.

Functionalization of Fe₃O₄ MNPs with VS

Vinyl groups were attached to the surfaces of the Fe₃O₄ MNPs via a 1-vinyltriethoxysilane precursor as follows. First, 1.0 g of Fe₃O₄ MNPs and 4.2 mmol (0.5 mL) of VS were completely combined in dry toluene (35 mL) and then sonicated for an additional 20 min. The mixture was refluxed for 24 h in a nitrogen environment. Afterward, the mixture was cooled to room temperature, and the vinyl-modified Fe₃O₄ MNPs were separated via an external magnetic field. The mixture was washed with toluene and ethanol to remove the remaining organosilane precursor and finally dried under reduced pressure at 50 °C (Scheme 1b).

Synthesis of the Fe₃O₄@VS-APS brush solid acid

The nanocomposite was synthesized via free radical polymerization, utilizing Fe₃O₄@VS as a vinyl containing support to polymerize with the APS monomer. First, 3 g of APS was dissolved in 70 mL of hot ethanol. Separately, 70 mL of ethanol solution including 1.2 g of Fe₃O₄@VS was subjected to ultrasonic waves for 20 min and added to the APS solution. The resulting mixture was heated to 75 °C. To conduct the polymerization reaction, 0.4 g of BP was subsequently dissolved in 15 mL of hot ethanol and added to the reaction mixture. Reflux was carried out under a nitrogen atmosphere for 6 h to complete the polymerization reaction. Once the polymerization finished, the product was separated via a simple magnet and washed with ethanol several times. Finally, the Fe₃O₄@VS-APS brush solid acid was dried under vacuum for 4 h at 50 °C (Scheme 1c).

The acidity of the Fe₃O₄@VS-APS brush solid acid

The sulfonic acid group concentration was accurately determined via ion-exchange pH analysis^47,56. Fe₃O₄@VS-APS brush solid acid (50 mg) was introduced into a 25 mL aqueous solution of NaCl (1 M). The resulting mixture was agitated for 3 days. Titration was subsequently performed on the obtained solutions using NaOH (0.02 M). The acid content of the Fe₃O₄@VS-APS brush solid acid was measured to be 0.4 mmol g^− 1.

General procedure for the synthesis of 3,4-dihydropyrimidin-2-ones(thiones)

A solution containing aldehyde (1 mmol), methyl acetoacetate (1 mmol), urea/thiourea (1.3 mmol) and Fe₃O₄@VS-APS brush solid acid (0.05 g) (0.12 g in the case of thiourea) was agitated at 100 °C for a suitable time under solvent-free conditions (Table 2). The progress of the reaction was tracked via thin-layer chromatography (TLC). Upon completion of the reaction, the mixture was washed with water (3 × 10 mL). Ultimately, the mixture was dissolved in heated ethanol and the catalyst was isolated via magnetic decantation. The crude product was further purified via recrystallization using ethanol or preparative thin-layer chromatography via silica gel.

Table 2.

Substrate scope for the synthesis of 3,4-dihydropyrimidin-2-ones/thiones^a.

Entry	Aldehyde	X	Time (h[min])	Yield (%)b	Product
1		O	1 [50]	92
2		O	1 [45]	93
3		O	2	91
4		O	2	90
5		O	2 [15]	90
6		O	2 [30]	87
7		O	2 [30]	88
8		O	1 [50]	91
9		O	1 [50]	85
10		O	3 [45]	88
11		O	1 [50]	89
12		S	7	90c
13		S	7	91c
14		S	8	90c
15		S	7	89c
16		S	8 [25]	89c
17		S	9 [15]	85c
18		S	7 [10]	90c

^aReaction conditions: aldehyde (1 mmol), methyl acetoacetate (1 mmol), urea or thiourea (1.3 mmol) and Fe₃O₄@VS-APS brush solid acid (0.05 g) at 100 °C. ^bIsolated yields and the structures of the products were confirmed by¹H-NMR and¹³C-NMR spectral data (Refer to Supplementary Information). ^cReaction was carried out using 0.12 g of Fe₃O₄@VS-APS brush solid acid.

Results and discussion

Catalyst characterization

Figure 3 shows the infrared spectra of Fe₃O₄, Fe₃O₄@VS and Fe₃O₄@VS-APS. The absorption band at 594 cm^− 1 confirms the existence of Fe₃O₄, which is observed in all samples and can be attributed to Fe–O stretching vibrations⁵⁷. The two absorption peaks observed at 1042 and about 3300 cm^− 1 correspond to the stretching vibrations of the –Si–O and –Si–OH bonds, respectively (Fig. 3b and c)⁵⁷. These peaks affirm that the 1-vinyltriethoxysilane precursor was successfully coated on the surface of the Fe₃O₄ MNPs core. In the spectrum of the Fe₃O₄@VS-APS brush solid acid (Fig. 3c), the absorption peaks at around 2957 and 2867 cm^− 1 are attributed to asymmetric and symmetric aliphatic –C–H bonds⁵⁷. The strong absorption peak at 1642 cm^− 1 is attributed to the C = O bond⁵⁸. Additionally, the absorption peak at 1545 cm^− 1 is attributed to the bending vibration of the N‒H bond⁵⁸. Additionally, the weak absorption peaks in the 1200–1400 and 3366 cm^− 1 regions are attributed to sulfonic acid functional groups⁵⁸.

Fig. 3.

FT-IR spectra of (a) Fe₃O₄ (b) Fe₃O₄@VS and (c) Fe₃O₄@VS-APS.

Figure 4 displays the XRD patterns of the Fe₃O₄ MNPs and Fe₃O₄@VS-APS brush solid acid. The XRD patterns in both Fig. 4a and b show that the Fe₃O₄ MNPs core have six distinct XRD peaks at 2θ values of 30.2°, 35.6°, 43.2°, 53.6°, 57.2°, 62.9°, 71.2° and 74.1°. These peaks correspond to the crystallographic planes (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1), (4 4 0), (6 2 0) and (5 3 3) of Magnetite, respectively. This confirms that the Fe₃O₄ MNPs are pure and have a crystalline cubic spinel structure, as indicated by the JCPDS database file No. 19-0629⁵⁷. In the XRD pattern of Fe₃O₄@VS-APS brush solid acid (Fig. 4b), in addition to the usual reflections of Fe₃O₄ MNPs, there are weak XRD peaks at 11.90°, 16.65° and 18.15°.

Fig. 4.

XRD patterns of the (a) Fe₃O₄ MNPs and (b) Fe₃O₄@VS-APS brush solid acid.

These peaks are caused by the presence of a silica shell that coats the Fe₃O₄ MNPs core⁵⁷. Despite the polymeric shell being coated on the Fe₃O₄ MNPs core, the characteristic XRD peaks for both amorphous silica and magnetite were maintained, with only minor alterations in the Bragg intensity. The results indicate that the structure of the spinel ferrite Fe₃O₄ MNPs is intact in Fe₃O₄@VS-APS brush solid acid, suggesting that the magnetic properties are preserved following surface functionalization with the polymeric shell, as supported by other characterization results.

Figure 5 displays the energy-dispersive X-ray spectroscopy (EDX) spectrum of the Fe₃O₄@VS-APS brush solid acid. The Fe₃O₄@VS-APS brush solid acid contained carbon (C), oxygen (O), silicon (Si), iron (Fe), nitrogen (N), and sulfur (S) with atomic percentages of approximately 17.78%, 43.80%, 1.13%, 32.67%, 2.22%, and 2.40%, respectively.

Fig. 5.

EDX spectrum of the Fe₃O₄@VS-APS brush solid acid.

The morphology of the Fe₃O₄@VS-APS brush solid acid was analyzed by scanning electron microscopy (SEM). Figure 6, shows that the SEM images of the Fe₃O₄@VS-APS brush solid acid show an approximately uniform distribution of spherical particles with an average diameter of around 57 nm. Additionally, the images also reveal the presence of particle agglomerations, which can be attributed to the magnetic forces between the particles.

Fig. 6.

Representative SEM images of the Fe₃O₄@VS-APS brush solid acid at two magnifications: (a) 1 μm and (b) 500 nm.

Figure 7 displays transmission electron microscopy (TEM) images of the Fe₃O₄@VS-APS brush solid acid. The images revealed a distinct visual contrast between the magnetic core and its surrounding siliceous and organic shells, which appeared as black and lighter areas, respectively. This observation confirms that the Fe₃O₄ MNPs core was effectively coated by the polymeric shell, resulting in the formation of a core-shell structure.

Fig. 7.

Representative TEM images of the Fe₃O₄@VS-APS brush solid acid at two magnifications: (a) 50 nm and (b and c) 100 nm.

The magnetic characteristics of the Fe₃O₄ MNPs and Fe₃O₄@VS-APS brush solid acid were determined by vibrating sample magnetometer (VSM), and the magnetization curves at room temperature are shown in Fig. 8a. The isothermal magnetization curves exhibited a significant and rapid increase as the applied magnetic field increased. The magnetization curves did not reveal any remanence or coercivity, thus verifying the superparamagnetic characteristics of the Fe₃O₄@VS-APS brush solid acid. The Fe₃O₄ MNPs and Fe₃O₄@VS-APS brush solid acid exhibited saturation magnetizations of 66.9 and 29.1 emu/g, respectively. Despite a decrease in the saturation magnetization value following the addition of siliceous and polymeric acidic shells, the resulting solid catalyst maintained an optimal degree of magnetic responsiveness for the purpose of magnetic separation.

Fig. 8.

(a) Magnetization curves of the Fe₃O₄ (blue dashed line) and Fe₃O₄@VS-APS (black line) magnetic samples and (b) photographs depicting the Fe₃O₄@VS-APS suspensions (i) prior to and (ii) subsequent to magnetic separation.

The Fe₃O₄@VS-APS brush solid acid that was produced may be effortlessly dispersed in the reaction mixture through slight shaking, without any indications of agglomerations, resulting in a solution that is uniformly spread. In addition, by placing an external magnet next to the reaction flask, the Fe₃O₄@VS-APS brush solid acid may be quickly and completely separated (Fig. 8b). This method is advantageous for efficiently recovering the catalyst from the reaction mixture. Therefore, the Fe₃O₄@VS-APS brush solid acid offers an easy way to separate it from the liquid reaction mixture because of its heterogeneous nature and magnetic properties. In other words, the Fe₃O₄ component of the Fe₃O₄@VS-APS brush solid acid possesses magnetic properties, allowing easy separation from the reaction mixture and subsequent recycling for reuse.

To evaluate the successful loading of the vinylsilane precursor and organic brush polymer shells as well as the thermal stability of the Fe₃O₄@VS-APS brush solid acid, TGA/DTG analysis was performed. Figure 9 displays the thermogravimetric and differential thermal analysis thermograms of Fe₃O₄@VS and Fe₃O₄@VS-APS. The magnetic Fe₃O₄@VS and Fe₃O₄@VS-APS samples underwent thermal decomposition resulting in total weight losses of 9.07% and 21.80%, respectively. In both samples, the initial thermal degradation, spanning from ambient temperature to 200 °C, can be ascribed to the evaporation of physically adsorbed water onto the specimens³². The subsequent weight losses between 200 and 800 °C can be attributed to the decomposition of organic moieties coated on the Fe₃O₄ MNPs^59,60. Owing to the decomposition of the polymer brushes coated onto the surface of the Fe₃O₄ MNPs, the TGA/DTG thermogram of the Fe₃O₄@VS-APS brush solid acid (Fig. 9b) revealed greater weight loss than did the TGA/DTG thermogram of Fe₃O₄@VS (Fig. 9a). Therefore, it was evident from the TGA/DTG thermograms that the Fe₃O₄@VS-APS brush solid acid was prepared successfully and had good thermal stability, demonstrating its feasibility for the Biginelli reaction.

Fig. 9.

TGA/DTG thermograms of the (a) Fe₃O₄@VS and (b) Fe₃O₄@VS-APS magnetic samples.

Catalytic performance of the Fe₃O₄@VS-APS brush solid acid for the Biginelli reaction

In this research, a magnetic brush polymer-supported sulfonic acid nanocomposite was synthesized and utilized as an acidic catalyst for the Biginelli reaction. A variety of aldehydes, including substituted aromatic aldehydes, aliphatic aldehydes, heterocyclic aldehydes, and aldehydes containing polycyclic aromatic hydrocarbons, were chosen and combined with methyl acetoacetate and urea(thiourea) to produce 3,4-dihydropyrimidine-2-ones(thiones).

To assess this reaction, the optimal reaction conditions, including the choice of temperature, and catalyst quantity, were determined. To achieve these objectives, the model reaction used was a reaction involving benzaldehyde (1.0 mmol), methyl acetoacetate (1.0 mmol), and urea (1.3 mmol) as substrates. The model reaction was carried out under various temperatures and quantities of brush solid acid.

First, we treated the model substrates with each other in the presence of 0.2 g of Fe₃O₄@VS-APS brush solid acid at room temperature under solvent-free conditions. Only a 6% yield of the desired product was observed even after 15 h (Table 1, entry 1). To determine the optimal reaction temperature, the model reaction was tested by increasing the temperature with 0.2 g of brush solid acid under solvent-free conditions. The study revealed that the production of the desired 3,4-dihydropyrimidin-2-one was increased when the temperature was increased, resulting in shorter reaction durations (Table 1, entries 2–4). After that, with the green chemistry approach, the reaction was carried out by reducing the amount of the Fe₃O₄@VS-APS brush solid acid at 70 °C. At the same time, a lower yield of the desired 3,4-dihydropyrimidin-2-one was obtained (Table 1, entry 5). Thus, the model reaction was carried out at higher temperatures without any change in catalyst loading. An increase in the desired 3,4-dihydropyrimidin-2-one was observed with shorter reaction times (Table 1, entries 6 and 7). To determine the importance of the amount of brush solid acid in the reaction, the effect of less loading of brush solid acid was subsequently investigated at constant and different reaction temperatures for 110 min. At a constant reaction temperature, a lower yield of the expected 3,4-dihydropyrimidin-2-one was obtained, but when the reaction temperature was increased to 100 °C, a good yield of the product was obtained (Table 1, entries 8 and 9). Moreover, the reaction was investigated without the presence of brush solid acid, which resulted in a minimal product yield even after 15 h (Table 1, entry 10). Finally, the reaction was conducted in the presence of the Fe₃O₄ MNPs under optimal conditions, resulting in a yield of only 29% (Table 1, entry 11). On the basis of the data in Table 1 and with the green chemistry approach, the appropriate result is obtained when the reaction is carried out under optimal conditions, i.e., a temperature of 100 °C, 0.05 g of Fe₃O₄@VS-APS brush solid acid, 110 min and no solvent (Table 1, entry 9).

Table 1.

Optimization of the reaction temperature and amount of the Fe₃O₄@VS-APS brush solid acid for the model reactions of benzaldehyde, methyl acetoacetate and urea^a.

Entry	Brush solid acid (g)	Temperature (°C)	Time (h[min])	Yield (%)b
1	0.2	r.t.	15	6
2	0.2	50	3 [30]	53
3	0.2	60	3 [30]	71
4	0.2	70	2 [45]	82
5	0.1	70	2 [45]	70
6	0.1	80	1 [50]	84
7	0.1	90	1 [50]	93
8	0.05	90	1 [50]	85
9	0.05	100	1 [50]	92
10	-	100	15	9
11c	-	100	1 [50]	29

^aReaction conditions: benzaldehyde (1 mmol), methyl acetoacetate (1 mmol), and urea (1.3 mmol). ^bIsolated yields. ^cReaction was carried out using 0.05 g of Fe₃O₄ MNPs under optimal conditions. Significant values are in bold.

To determine the extent of the Biginelli reaction under optimal reaction conditions in the presence of Fe₃O₄@VS-APS brush solid acid, aliphatic, substituted aromatic and heterocyclic aldehydes were used to react with urea and methyl acetoacetate. The desired 3,4-dihydropyrimidin-2-ones(thiones) were obtained with high efficiency and rapid reaction times, as shown in Table 2. The reactions of aromatic aldehydes, which possess either electron-donating (meta methyl, para isopropyl, meta hydroxy and para methoxy benzaldehydes (Table 2, entries 4–7)) or electron-withdrawing (para fluoro and meta bromo benzaldehydes (Table 2, entries 2–3)) substituents at the meta, and para positions, result in exceptional yields, as shown in Table 2. Therefore, inserting a significant number of substitution patterns on the aryl ring that are pharmacologically relevant with a high level of efficiency is possible^35–37. Although the use of aliphatic aldehydes in the Biginelli reaction often results in a low yield, in this study, a good yield of the corresponding 3,4-dihydropyrimidin-2-one was obtained (Table 2, entry 10). Furthermore, even aromatic aldehydes with high steric hindrance such as 1-naphthaldehyde and anthracene-10-carbaldehyde, which may be relatively difficult to react with, exhibited good reactivity (Table 2, entries 8 and 9). Another remarkable feature of this method is that even with the use of heterocyclic thiophene-2-carbaldehyde, a good yield of the desired 3,4-dihydropyrimidin-2-one has been obtained. In addition, thiourea has been effectively employed to yield equivalent 3,4-dihydropyrimidin-2-thiones, which have attracted significant attention because of their biological properties^48,49. All the reactions proceeded smoothly and afforded the corresponding products in good yields (Table 2, entries 12–18).

With these results in hand and continuing our research on the evaluation of three-component reactions using new solid acids, we then investigated the efficiency of Fe₃O₄@VS-APS brush solid acid in the Strecker reaction for the synthesis of α-aminonitriles, which are intermediates in the synthesis of various amino acids, nitrogen-containing heterocycles and other physiologically and pharmacologically active compounds (Fig. 10)^61–64.

Fig. 10.

Chemical structures of three distinct types of pharmacologically active α-aminonitriles synthesized through the Strecker reaction, which serves as a fundamental step in the process.

To this end, the Strecker reaction under investigation involved the condensation of benzaldehyde (1.0 mmol), aniline (1.0 mmol), and trimethylsilyl cyanide (TMSCN) (1.2 mmol), in the presence of 0.05 g of Fe₃O₄@VS-APS brush solid acid at room temperature for 15 min under solvent-free conditions, affording the corresponding α-aminonitrile in 96% isolated yield (Scheme 2).

Scheme 2.

Strecker reaction utilizing Fe₃O₄@VS-APS brush solid acid.

Given the promising performance of the Fe₃O₄@VS-APS brush solid acid in the Biginelli and Strecker reactions, we investigated the ability of the Fe₃O₄@VS-APS brush solid acid to catalyze the esterification of 1-octanol with glacial acetic acid to produce octyl acetate. For this purpose, in a typical experiment, 1-octanol was mixed with acetic acid glacial at a ratio of 1:6 in the presence of 0.05 g of Fe₃O₄@VS-APS brush solid acid at 70 °C and stirred under solvent free conditions. After 24 h, the desired ester was extracted and obtained in 93% yield (Scheme 3).

Scheme 3.

The catalytic esterification of 1-octanol with glacial acetic acid.

Considering that a heterogeneous catalyst was used in this research to investigate the reactions, a study was carried out on catalyst reusability in reactions involving benzaldehyde (1.0 mmol), methyl acetoacetate (1.0 mmol), and urea (1.3 mmol) in the presence of Fe₃O₄@VS-APS brush solid acid (0.05 g) at 100 °C under solvent-free conditions. After the completion of the reaction, Fe₃O₄@VS-APS brush solid acid was separated with an external magnet, washed with ethanol (3 × 5 mL), and dried at 90 °C under vacuum. The catalyst was subsequently utilized in subsequent runs. The findings indicated that the catalyst exhibited consistent performance for a minimum of four consecutive cycles, with minimal degradation in its catalytic efficacy, which proves the effectiveness of the proposed catalyst for the Biginelli reaction (Fig. 11).

Fig. 11.

Reusability assessment of the Fe₃O₄@VS-APS brush solid acid.

Since Fe₃O₄@VS-APS brush solid acid was utilized in the Biginelli reaction, it is important to demonstrate its contribution to promoting the reaction. On the basis of the proposed mechanisms in the literature for the Biginelli reaction^36,37,66, three main mechanisms are accepted: iminium, enamine, and Knoevenagel. The reaction pathway is related to the catalytic system used and the reaction conditions. A plausible reaction pathway for the Fe₃O₄@VS-APS brush solid acid-catalyzed Biginelli reaction appears to proceed through the following sequence. Protonation of the carbonyl aldehyde group by the sulfonic acid sites of the catalyst creates an electrophilic center at the carbonyl carbon. A nucleophilic attack occurs by urea, producing a Schiff base (I), followed by protonation of the Schiff base (I) to produce an iminium intermediate (II). The reaction of iminium with the enol form of methyl acetoacetate provides intermediate (III), followed by cyclization (IV) and finally dehydration to produce 3,4-dihydropyrimidin-2-one (V) (Scheme 4).

Scheme 4.

Proposed mechanism for the Fe₃O₄@VS-APS brush solid acid-catalyzed Biginelli reaction.

To explore further, we conducted a comparative analysis of the catalytic efficiency of the Fe₃O₄@VS-APS brush solid acid to other catalytic systems described in the literature^65–69.

The reaction under investigation involved the condensation of benzaldehyde, methyl acetoacetate, and urea as outlined in Table 3. The findings illustrate the benefits of this method in comparison with some previously documented methodologies, especially with respect to the amount of catalyst. Notably, the Fe₃O₄@VS-APS brush solid acid catalyzed the reaction in the absence of any organic solvent and in a short reaction time. Additionally, it should be highlighted that, the balance of hydrophobic (due to the non-polar nature of the organic polymer structure of the catalyst) and hydrophilic (due to the polar sulfonic acid active sites) groups on the catalyst surfaces facilitates the mass transfer of the polar or non-polar reactants during the reaction. Moreover, the Fe₃O₄@VS-APS brush solid acid is more easily magnetically recovered in comparison to the other catalysts.

Table 3.

Comparison of different catalytic systems in the Biginelli reaction.

Entry	Catalyst	Catalyst (mg)	Solvent	Temp. (°C)	Time (h)	Yield (%)	Ref.
1	HNTS-BOA	150 mg	CH3CN	Reflux	36	69	66
2	Nb2O5/T	56 mg	Solvent-free	130 °C	1	94	67
3	NiO nanocatalyst	60 mg	Solvent-free	90 °C	1.5	92	68
4	CuFe2O4	83 mg	Solvent-free	50 °C	< 1	92	69
5	Coconut husk ash twisted graphene	100 mg	Solvent-free	130 °C	< 1	93	70
6	Fe3O4@VS-APS brush solid acid	50 mg	Solvent-free	100 °C	< 2	92	This work

Conclusions

In conclusion, in the present study, a new magnetic brush catalyst functionalized with sulfonic acid active sites, named the Fe₃O₄@VS-APS brush solid acid, was designed and synthesized. The expected structure and properties of the catalyst were confirmed through various experimental and instrumental methods. The performance of the brush solid acid was evaluated in three acid-catalyzed reactions: Biginelli, Strecker, and esterification. The desired products were successfully obtained in high purity and excellent yields under solvent-free conditions. The magnetic susceptibility of the catalyst facilitates its isolation and reuse in reactions. Additionally, the brush-like polymer structure of the catalyst enhances the interaction of the sulfonated surfaces with the reactants, leading to increased exposure to acidic active sites and improved reaction yields. The Fe₃O₄@VS-APS brush solid acid was successfully reused in four consecutive reactions without any significant decrease in yield, demonstrating its capacity for endurance during recycling procedures. Finally, according to the mentioned advantages, Fe₃O₄@VS-APS brush solid acid showed superior activity compared with some existing documented catalysts. These capabilities indicate the potential of sulfonated polymeric brush-like catalysts as promising new eco-friendly options for hybrid catalyst materials to further explore acid-catalyzed reactions.

Electronic supplementary material

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Author contributions

A. M.: Supervision, Conceptualization, Resources, Writing Original Draft, Review & Editing, Visualization, Investigation, Formal analysis; M. H.: Conceptualization, Review & Editing, Formal analysis; H. M.: Performed the experiments; M. P.: Performed the experiments and Formal analysis; A. T.: Performed the experiments.

Data availability

The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information files. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request. Source data are provided with this paper.

Declarations

Competing interests

The authors declare no competing interests.