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. 2025 Nov 17;15:40058. doi: 10.1038/s41598-025-25743-5

Nanomagnetic 4-amino-3-hydroxynaphthalene-1-sulfonic as an efficient heterogeneous catalyst for multicomponent synthesis of 2-amino-3-cyano-4,6-diarylpyridines under green conditions

Maha Abdallah Alnuwaiser 1, Ishraga GalalEldin Abdalla Awad 2, MAI MOUSA MAHMOUD ALHEJOJ 3,✉, Ahmed Mohajja Alshammari 4, Mohmed Ahmed Habib 5, Saad Alrashdi 6
PMCID: PMC12623813  PMID: 41249479

Abstract

Herein, we report the synthesis and application of a novel, magnetically retrievable sulfonic acid functionalized solid catalyst, prepared by immobilizing α-amino-3-hydroxynaphthalene-1-sulfonic acid onto alkyl halide-coated Fe3​O4​ magnetic nanoparticles. Comprehensive characterization confirmed its structure, morphology, and properties. Its catalytic efficacy was evaluated in the one-pot multicomponent cyclocondensation for polysubstituted pyridine derivatives, specifically 2-amino-3-cyano-4,6-diarylpyridines. This green and efficient protocol, utilizing aldehydes, ketones, malononitrile, and ammonium acetate in a water/ethanol mixture, achieved high yields, excellent functional group tolerance, and no byproduct formation. Furthermore, the catalyst exhibited remarkable reusability, remaining effective for at least five consecutive cycles through simple magnetic separation. This innovative catalyst provides a practical and efficient method for producing diverse heterocyclic compounds relevant to medicinal chemistry.

Keywords: Nanomagnetic acid catalyst; Polysubstituted pyridines; 2-amino-3-cyano-4,6-diarylpyridines; Multicomponent reactions; Green chemistry

Subject terms: Chemistry, Materials science

Introduction

Pyridine derivatives are a prominent class of heterocyclic compounds indispensable in organic chemistry1. Their unique nitrogen-containing six-membered aromatic ring makes them crucial building blocks for synthesizing a vast array of pharmaceuticals and agrochemicals2. The ability to control the chemical and biological properties of these materials often hinges on the presence and placement of substituents on the pyridine ring3–5. Consequently, the efficient synthesis of substituted pyridines remains a vibrant and essential area of research. Traditionally, substituted pyridines were often synthesized through post-synthetic modification of the aromatic ring. However, increasing the number of substituents and their introduction onto special positions on targeted molecules using these methods typically leads to more complex, lengthy, and costly synthetic routes6–9. In contrast, multicomponent reactions (MCRs) have emerged as pioneering methods, enabling the one-pot synthesis of pyridines with specific substituents10,11. The benefits of MCRs become even more pronounced as the degree of substitution increases, significantly simplifying the overall synthesis12–14.

Over the past two decades, the synthesis of polysubstituted pyridines has garnered significant attention15–20. Among the most important reactions for this purpose is the cyclo-condensation of aryl methyl ketones, arylaldehydes, active methylene compounds (such as malononitrile), and a nitrogen source (like ammonium acetate). This reaction efficiently generates 2-amino-3-cyano-4,6-diarylpyridines as biologically active materials21–23. While numerous methodological studies have focused on this synthesis, many reported approaches suffer from drawbacks such as harsh reaction conditions, the use of toxic materials, expensive catalysts with homogeneous nature, metal leaching, and often prolonged reaction times leading to low yields23–26. Therefore, there is a clear and pressing need to develop greener and more efficient methodologies for the synthesis of polysubstituted pyridines in organic chemistry.

The shift from homogeneous to heterogeneous catalysts has become increasingly important in recent years due to compelling environmental and economic factors27,28. The core advantage of heterogeneous catalysts lies in their use of solid catalyst supports that effectively stabilize the catalytic species29. Among the diverse range of solid supports, including silica30, Boehmite31, and carbon materials32, magnetic nanomaterials stand out33. They are highly favored due to their facile recyclability via an external magnetic field and their inherently high surface area, which enhances catalytic activity34–38.

Concurrently, solid acid catalysts have garnered significant attention, particularly for their efficiency in multicomponent reactions39–42. However, many reported solid acid catalysts are based on sulfuric acid, often immobilized on supports using harsh reagents like chlorosulfonic acid for sulfonation31,42–46. These methods typically involve severe conditions, specialized handling, and can produce corrosive gases such as HCl. This highlights a clear need for the development of safer and greener acid catalysts. Utilizing organic moieties containing acid sites presents a particularly interesting avenue in this regard.

Building on these insights, our ongoing research aims to integrate the benefits of organic acids with nanomagnetic particles by covalently bonding them to the support surface. This approach seeks to create a sustainable and efficient catalyst for various organic reactions. Specifically, we employed Fe3O4 magnetic nanoparticles (MNPs) as the support. Their surface was functionalized with alkyl halide sites to immobilize 4-amino-3-hydroxynaphthalene-1-sulfonic acid. This particular organic acid was chosen for its dual functionality: its free amine groups facilitate bonding to the alkyl halide containing linker on the MNPs surface, while its SO3H group provides the essential acid site. We then thoroughly investigated the catalytic activity of this novel material in the synthesis of 2-amino-3-cyano-4,6-diarylpyridines under green conditions, aiming to establish a sustainable synthetic methodology.

Experimental

Typical procedure for synthesis of Fe3O4@PTMS-AHNS solid acid catalyst

Initially, Fe3O4 MNPs were synthesized via the co-precipitation of FeCl2.4H2O and FeCl3.6H2O in an aqueous medium using ammonium hydroxide, following a previously reported procedure. Subsequently, 5 g of the as-prepared Fe3O4 MNPs were dispersed in 150 mL of toluene and sonicated for 30 min. Then, 7 mL of (3-chloropropyl)trimethoxysilane (CPTMS) was added dropwise to the reaction mixture under continuous stirring over 30 min, followed by refluxing at 80 °C for 48 h. The resulting Fe3O4@CPTMS product was magnetically separated using a neodymium magnet, washed thoroughly with n-hexane, and dried at 80 °C for 4 h. In the next step, 5 g of Fe3O4@CPTMS was dispersed in 100 mL of DMF and sonicated for 1 h. A separately prepared solution of 15 mmol 4-amino-3-hydroxynaphthalene-1-sulfonic acid and 20 mmol K₂CO₃ in 100 mL of DMF was then added to the dispersion, and the mixture was refluxed for 48 h under constant stirring. The final product was isolated by magnetic separation, washed repeatedly with DMF, distilled water, and ethanol, and dried at 80 °C for 4 h to afford the Fe3O4@PTMS-AHNS solid acid catalyst.

General procedure for the synthesis of polysubstituted pyridines catalyzed by over the catalysis of Fe3O4@PTMS-AHNS

A mixture of arylaldehyde (1 mmol), acetophenone (1 mmol), malononitrile (1.1 mmol), ammonium acetate (1.8 mmol), Fe3O4@PTMS-AHNS nanocomposite (25 mg), and a solvent system of water/ethanol (1:2, 5 mL) was added to a round-bottom flask. The reaction mixture was stirred under reflux conditions until completion, as monitored by thin-layer chromatography (TLC). Upon completion, the reaction mixture was diluted with boiling ethanol, and the catalyst was separated by magnetic decantation. The solvent was then partially evaporated under reduced pressure, and the crude product was purified by recrystallization from ethanol.

Results and discussions

The Fe3O4@PTMS-AHNS nanocomposite was synthesized through a straightforward three-step procedure on a multigram scale. The process involved the preparation of Fe3O4 nanoparticles, followed by surface functionalization with CPTMS as the alkyl halide source. In the final step, a nucleophilic substitution reaction was performed between the chloropropyl-functionalized surface and the amine group of 4-amino-3-hydroxynaphthalene-1-sulfonic acid under basic conditions, yielding the desired solid acid catalyst (Scheme 1).

Scheme 1.

Scheme 1

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Stepwise synthesis of Fe3O4@PTMS-AHNS nanocomposite.

Catalyst characterization

Following the successful synthesis of the Fe3O4@PTMS-AHNS nanocomposite, its physicochemical properties were comprehensively characterized using several analytical techniques.

The progressive changes in chemical bands and functional groups during the synthesis and surface functionalization of Fe3O4, Fe3O4@CPTMS, and Fe3O4@PTMS-AHNS nanocomposites were monitored by Fourier transform infrared spectroscopy (FT-IR) as presented in Fig. 1. The FT-IR spectrum of bare Fe3O4 nanoparticles displays a broad absorption band at 3441 cm−1, attributed to O–H stretching vibrations of surface hydroxyl groups, and characteristic Fe–O stretching vibrations at 635 and 581 cm−1, consistent with previous literature reports47. Upon functionalization with CPTMS, the Fe3O4@CPTMS spectrum (curve b) shows new absorption bands at 2925 and 2863 cm−1, corresponding to aliphatic C–H stretching vibrations. Additionally, a broad band around 1050 cm−1, assigned to Si–O stretching vibrations, confirms the successful grafting of CPTMS onto the Fe3O4 surface48. In the final step, the FT-IR spectrum of the Fe3O4@PTMS-AHNS nanocomposite exhibits new peaks at 3060, 1582, 1462, 1351, and 1108 cm−1. These are assigned to aromatic C–H stretching, C = C stretching of the aromatic ring, Ar–NH vibrations, and characteristic SO3H stretching bands (S = O and S─O symmetric and a symmetric stretching vibrations)49, respectively, confirming the successful immobilization of the AHNS moiety and formation of the target nanocatalyst.

Fig. 1.

Fig. 1

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FT-IR spectra of (a) Fe3O4, (b) Fe3O4@CPTMS and Fe3O4@PTMS-AHNS nanocomposite.

The crystalline phase and structure of the Fe3O4@PTMS-AHNS nanocomposite were investigated using X-ray diffraction (XRD) analysis. The obtained XRD pattern (Fig. 2) displays eight distinct diffraction peaks at 2θ values of 30.33°, 35.88°, 43.48°, 44.68°, 54.18°, 57.68°, 63.28°, and 74.63°. These peaks are well-matched with the characteristic reflections of cubic Fe3O4 MNPs, corresponding to the (220), (311), (400), (331), (422), (511), (440), and (533) crystallographic planes, respectively, according to the standard JCPDS card No. 89–0691)50,51. These results confirm that the Fe3O4 nanoparticles retained their intrinsic spinel crystal structure during the Stepwise surface functionalization steps. This preservation of crystallinity indicates that the chemical functionalization occurred primarily on the nanoparticle surface without disturbing the crystalline core of the magnetite structure.

Fig. 2.

Fig. 2

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XRD pattern of Fe3O4@PTMS-AHNS nanocomposite.

The thermal stability and organic content of the Fe3O4@PTMS-AHNS nanocomposite were investigated using Thermogravimetric Analysis-Differential Scanning Calorimetry (TGA-DSC). The TGA curve revealed an initial weight loss of approximately 0.66% below 200 °C, accompanied by a broad endothermic event in the DSC curve (Fig. 3). This minor weight loss is attributed to the evaporation of physisorbed water and residual solvents, suggesting efficient drying of the nanocomposite after synthesis. A more significant weight loss of approximately 6.31% was observed in TGA curve between 200 °C and 500 °C. This range featured a prominent exothermic peak around 360–380 °C, followed by another broad exothermic process extending up to approximately 500 °C in DSC curve. These exothermic events correspond to the thermal decomposition of the organic PTMS-AHNS components grafted onto the surface of the Fe3O4 nanoparticles and confirms the formation of targeted nanocomposite (Fig. 3, 4).

Fig. 3.

Fig. 3

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TGA and DSC analysis of Fe3O4@PTMS-AHNS nanocomposite.

Fig. 4.

Fig. 4

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EDX analysis of Fe3O4@PTMS-AHNS nanocomposite.

Energy-dispersive X-ray (EDX) spectroscopy was employed to determine the elemental composition of the Fe3O4@PTMS-AHNS nanocomposite (Fig. 4). The analysis confirmed the presence of iron (60.77 Wt%, 31.16 at%) and oxygen (26.36 Wt%, 47.17 at%) as the primary constituents of the nanomagnetic catalytic support. The successful surface functionalization with CPTMS was corroborated by the detection of silicon (3.34 wt%, 3.41 at%). Furthermore, the presence of carbon (5.88 wt%, 14.01 at%), nitrogen (0.86 wt%, 1.76 at%), and sulfur (2.79 wt%, 2.50 at%), coupled with the absence of chlorine, collectively confirm the successful functionalization of Fe3O4@CPTMS with AHNS and the subsequent formation of the Fe₃O₄@PTMS-AHNS nanocomposite.

The spatial distribution of elements within the Fe3O4@PTMS-AHNS nanocomposite was thoroughly investigated using elemental mapping analysis (Fig. 5). The resulting elemental maps clearly illustrate the distribution and relative concentrations of the constituent elements. As anticipated, iron and oxygen exhibited the highest concentrations, consistent with their role as the primary components of the nanomagnetic catalytic support. Crucially, their uniform distribution throughout the sample suggests a homogeneous magnetic core. Silicon, carbon and nitrogen were observed with lower relative densities compared to iron and oxygen, which is expected given their incorporation as part of the surface functionalization. In contrast, sulfur as the source of sulfonic acid source displayed a notable and uniform distribution across the sample surface. The homogeneous and accessible distribution of this site is particularly significant, as it suggests excellent accessibility for guest reactants on the catalyst surface. This characteristic is highly beneficial for catalytic applications, indicating that the active sites are readily available for interaction.

Fig. 5.

Fig. 5

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EDX elemental mapping images of Fe3O4@PTMS-AHNS nanocomposite.

The morphology and particle size distribution of the Fe3O4@PTMS-AHNS nanocomposite were investigated using Scanning Electron Microscopy (SEM), as presented in Fig. 6. The SEM images clearly show that the nanoparticles possess a spherical to near-spherical morphology. A noticeable agglomeration of these particles is observed, which is most likely a consequence of the surface functionalization with PTMS-AHNS. Analysis of individual primary particles indicates a size distribution ranging from approximately 44 nm to 90 nm, thereby confirming their nanoscale dimensions.

Fig. 6.

Fig. 6

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SEM images of Fe3O4@PTMS-AHNS nanocomposite.

TEM analysis, as shown in Fig. 7, provides detailed insights into the morphological structure, size, and distribution of the Fe3O4@PTMS-AHNS nanocomposite. The micrographs reveal generally spherical to irregularly shaped nanoparticles that predominantly appear as aggregates. Based on the obtained histogram the particles exhibit an average size of 4.92 nm, while the aggregates can be considerably larger (Fig. 8). The images distinctly display a multicomponent system with characteristic features of each constituent: a darker, internal layer consistent with the Fe3O4 support is clearly visible, decorated by a well-defined, lighter layer attributed to amorphous silicon and carbon. These structural observations confirm the successful formation of the targeted nanocomposite on the surface of Fe3O4.

Fig. 7.

Fig. 7

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TEM images of Fe3O4@PTMS-AHNS nanocomposite.

Fig. 8.

Fig. 8

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Particles size histogram of Fe3O4@PTMS-AHNS nanocomposite.

Vibrating Sample Magnetometry (VSM) was employed to characterize the magnetic properties of the Fe3O4@PTMS-AHNS nanocomposite at room temperature under an applied field of 1.5 Tesla (Fig. 9). The analysis revealed a saturation magnetization (Ms​) of 16.55 emu/g, signifying a robust magnetic capacity and superparamagnetic behavior for the synthesized material. A comparison with the reported Ms​ value for bare Fe3O4 (73 emu/g)52 indicated a reduction in magnetization following functionalization with PTMS and subsequent coating with AHNS. This decrease is attributed to the inherent non-magnetic nature of the immobilized layers, which act as a magnetic insulating barrier. Crucially, this reduction in Ms​ does not impair the essential magnetic functionality required for the separation from the reaction mixture, thereby confirming the successful coating process while maintaining the nanoparticles recyclability.

Fig. 9.

Fig. 9

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VSM analysis of Fe3O4@PTMS-AHNS nanocomposite.

Catalytic study

After successfully synthesizing and characterizing the catalyst’s structure and physiochemical features, its catalytic efficiency was evaluated in the synthesis of 2-amino-3-cyanopyridines. The cyclocondensation of 4-benzaldehyde with acetophenone, malononitrile, and ammonium acetate was chosen as the model reaction, and the reaction parameters were optimized by varying their conditions. Initially, blank tests were conducted without a catalyst and with Fe3O4 and Fe3O4@CPTMS as catalysts, but no significant product was observed. However, when Fe3O4@PTMS-AHNS was applied, the reaction began to progress. Increasing the catalyst loading from 5 to 25 mg enhanced the product yield to 83%. Further increasing the amount to 30 or 35 mg did not improve the reaction yield or time, so 25 mg was selected as the optimal catalyst amount. Next, the effect of the solvent was examined using environmentally friendly conditions, including solvent-free conditions, water, ethanol, and different mixtures of water and ethanol (1:1, 1:2, and 1:3 V/V). The tests showed that solvent-free conditions and pure water resulted in lower yields, while ethanol and its mixtures with water provided higher yields under standard conditions. The best results were obtained using a water/ethanol mixture (1:2 V/V). Afterward, the effect of temperature was investigated and no significant yield of the desired product was observed via TLC at room temperature, so reflux conditions were selected as optimal. Finally, based on the results summarized in Table 1, the optimal conditions were determined to be 25 mg of catalyst in a 1:2 V/V mixture of water and ethanol under reflux.

Table 1.

Optimization of the reaction conditions for synthesis of polysubstituted pyridines over the catalysis of Fe3O4@PTMS-AHNS.

graphic file with name 41598_2025_25743_Figa_HTML.gif
Entry Catalyst Amount of catalyst Solvent Temp. (°C) Time (min) Yield
(%) a, b
1 - - Ethanol Reflux 4 h N.R
2 Fe3O4 25 Ethanol Reflux 4 h Trace
3 Fe3O4@CPTMS 25 Ethanol Reflux 4 h Trace
4 Fe3O4@PTMS-AHNS 5 Ethanol Reflux 30 35
5 Fe3O4@PTMS-AHNS 10 Ethanol Reflux 30 61
6 Fe3O4@PTMS-AHNS 20 Ethanol Reflux 30 78
7 Fe3O4@PTMS-AHNS 25 Ethanol Reflux 30 83
8 Fe3O4@PTMS-AHNS 30 Ethanol Reflux 30 83
9 Fe3O4@PTMS-AHNS 35 Ethanol Reflux 30 83
10 Fe3O4@PTMS-AHNS 25 Solvent-free 80 30 27
11 Fe3O4@PTMS-AHNS 25 Water Reflux 30 67
12 Fe3O4@PTMS-AHNS 25 Water: Ethanol (1:1) Reflux 30 85
13 Fe3O4@PTMS-AHNS 25 Water: Ethanol (1:2) Reflux 30 93
14 Fe3O4@PTMS-AHNS 25 Water: Ethanol (1:3) Reflux 30 91
15 Fe3O4@PTMS-AHNS 25 Water: Ethanol (1:2) R.T. 30 Trace
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a isolated yield.

b reaction conditions: benzaldehyde (1.0 mmol), acetophenone (1.0 mmol), malononitrile (1.1 mmol), ammonium acetate (1.8 mmol) catalyst (mg) and solvent (5 mL).

To investigate the reaction scope of the optimized method, its efficiency and limitations in the synthesis of polysubstituted pyridines were examined using a series of various substituted aryl aldehydes. In general, all studied reactions provided the desired product in good to excellent yields. A comparison of the results shows that aldehydes bearing electron-withdrawing substituents reacted faster and provided higher yields compared to those with electron-donating groups. It is worth noting that increasing the steric hindrance near the aldehyde group decreased reactivity, confirming that the reaction is responsive to both the electronic and steric effects of the substituents (Table 2).

Table 2.

The scope of polysubstituted pyridines synthesis over the catalysis of Fe3O4@PTMS-AHNS.

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A plausible reaction pathway for the synthesis of polysubstituted pyridines catalyzed by Fe3O4@PTMS-AHNS as a solid acid catalyst is outlined in Scheme 2. This transformation is initiated by the protonation and activation of the carbonyl center of the aldehyde by the acidic sites of the catalyst. This activation leads to the Knoevenagel condensation of the aldehyde and malononitrile, forming the α,β-unsaturated intermediate (A) via the removal of a water molecule. Simultaneously, the ketone reacts with ammonium acetate to form enamine (B). These intermediates then react together through a 1,4-Michael addition mechanism, generating intermediate (C), which subsequently undergoes a Thorpe-Ziegler type cyclization to form a six-membered ring58. Subsequent cooperative geminal-vinylogous anomeric-based oxidation or O2 oxidation leads to the aromatization of this six-membered ring (intermediate F) to the pyridine (final product) via the removal of an H2 molecule as a gas.

Scheme 2.

Scheme 2

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The proposed reaction mechanism of polysubstituted pyridines synthesis over the catalysis of Fe3O4@PTMS-AHNS MNPs.

Reusability test

To demonstrate the heterogeneous nature and recoverability of Fe3O4@PTMS-AHNS MNPs, a reusability test was performed for five cycles using benzaldehyde as the model substrate under optimal reaction conditions. After the completion of each reaction cycle, the mixture was diluted with hot ethanol, and the catalyst was collected by magnetic separation. The recovered catalyst was then washed several times with hot ethanol and acetone and dried at room temperature. As shown in Fig. 10, the obtained yields confirmed that the Fe3O4@PTMS-AHNS catalyst can be reused at least five times with only a slight decrease in its catalytic efficiency. This demonstrates its stability, reproducibility, excellent recoverability, and reusability under the reaction conditions. Finally, the stability of the catalyst was comprehensively evaluated using FT-IR and SEM analyses. The FT-IR spectrum of the spent Fe3O4@PTMS-AHNS catalyst (Fig. 11) showed remarkable agreement with that of the fresh catalyst (Fig. 1), thereby confirming the exceptional stability of its functional groups throughout the catalytic process. Additionally, SEM analysis corroborated the catalyst’s morphological integrity. As depicted in Fig. 12, the spent catalyst morphology and particle size distributions closely match to the fresh catalyst patterns. This striking consistency indicates the complete preservation of the host framework, a stable size, and a consistent distribution profile. Consequently, these findings provide unequivocal evidence that the catalyst exhibits no structural degradation and remains robust under operational conditions.

Fig. 10.

Fig. 10

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The reusability of Fe3O4@PTMS-AHNS catalyst.

Fig. 11.

Fig. 11

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The FT-IR spectrum of the recovered Fe3O4@PTMS-AHNS catalyst.

Fig. 12.

Fig. 12

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The SEM images of the recovered Fe3O4@PTMS-AHNS catalyst.

Hot-filtration and leaching tests

To determine the nature of the catalyst and evaluate potential acid leaching, a hot filtration test and subsequent ICP-OES analysis were performed. After a 15-min reaction time, which resulted in a 71% product yield, the reaction mixture was diluted with boiling ethanol and catalyst was then rapidly separated from the hot solution via magnetic filtration. The filtrate was stirred under optimal conditions for an additional 30 min to check for further reaction. During this period, the conversion was negligible, with the final product yield increasing only slightly to 72%. This finding strongly suggests that no active catalytic species leached into the solution. To confirm these results, the filtrate was analyzed using ICP-OES. The analysis detected no sulfur or iron. The absence of iron confirms the complete removal of the catalyst by magnetic filtration, and the lack of sulfur indicates that the acidic functional groups remained covalently bound to the support, with no detectable leaching.

Comparison of catalytic activity

A comparison of the efficiency of the Fe3O4@PTMS-AHNS catalyst in the synthesis of polysubstituted pyridines, using benzaldehyde as the model substrate, is summarized in Table 3. The results indicate that the developed methodology provides higher yields under greener conditions and in shorter reaction times compared to the best recent reports on this synthesis. Additionally, this method utilizes a mixture of ethanol and water as a green solvent system, and the catalyst’s magnetic and heterogeneous nature makes it an excellent choice for simple separation from the reaction medium.

Table 3.

Comparison of Fe3O4@PTMS-AHNS catalytic efficiency in polysubstituted pyridines synthesis.

Entry Catalyst Time (min) Yield (%) Ref.
1 Fe3O4@g-C3N4-SO3H 15 72 59
2 [HO3S-PhospIL@SBA-15] 480 90 60
3 Fe3O4@TiO2@O2PO2(CH2)NHSO3H 20 90 61
4 CoFe2O4@TRIS@sulfated boric acid 35 73 62
5 Fe3O4@Ca(HSO4)2 5 85 63
6 Fe3O4@PTMS-AHNS 30 93 This work
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aIsolated yield.

Comparison of solid acid catalysts

A significant number of solid acid catalysts have been synthesized and applied in various organic transformations64. To demonstrate the novelty and advantages of the present study, the synthetic conditions for Fe3O4@PTMS-AHNS were compared with those of other well-established solid acid catalysts from the literature, as detailed in Table 4. Among these, silica sulfuric acid (SSA), stands out as a well-known solid acid catalyst64,65. Its preparation involves the treatment of silica with chlorosulfonic acid, a procedure widely recognized as the “Zolfigol method.” This technique has since been adopted for the sulfonation of other solid supports, such as boehmite66,67, Cellulose68, g-C3N469 and etc. A key drawback of these materials is the necessity for post-reaction separation methods, including filtration and centrifugation. To mitigate this issue, researchers have developed magnetic acid catalysts by integrating the Zolfigol method with magnetic nanoparticles. This approach has led to the creation of several catalysts, including Fe3O4@SSA70 and Hercynite sulfuric acid49, Hercynite@SSA41, zirconium ferrite@SSA71, tin ferrite@SSA42, cobalt ferrite@SSA72, zinc ferrite@SSA73 and etc64. However, these catalysts often exhibit limited stability and their synthesis typically relies on harsh reagents and conditions. For instance, the use of chlorosulfonic acid is challenging to handle and generates highly corrosive HCl gas as a byproduct. Conversely, our methodology provides a safer and more environmentally friendly alternative. Our catalyst possesses magnetic properties, allowing for easy separation. Crucially, our synthesis avoids the use of chlorosulfonic acid, instead employing an organic moiety that provides the necessary acid sites.

Table 4.

Comparison of several solid acid catalysts.

Entry Catalyst Sulfonation reagent Separation Ref.
1 SSA Chlorosulfonic acid Filtration 65
2 boehmite-SSA Chlorosulfonic acid Filtration 66,67
3 CSA Chlorosulfonic acid Filtration 68
4 g-C3N4·SO3H (BCNSA) Chlorosulfonic acid Filtration 69
5 Fe3O4@SSA Chlorosulfonic acid Magnetically 70
6 Hercynite@SA Chlorosulfonic acid Magnetically 49
7 Hercynite@SSA Chlorosulfonic acid Magnetically 41
8 Zirconium ferrite@SSA Chlorosulfonic acid Magnetically 71
9 Tin ferrite@SSA Chlorosulfonic acid Magnetically 42
10 cobalt ferrite@SSA Chlorosulfonic acid Magnetically 72
11 Zinc ferrite@SSA Chlorosulfonic acid Magnetically 73
12 Fe3O4@PTMS-AHNS 4-amino-3-hydroxynaphthalene-1-sulfonic acid Magnetically This work
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Conclusion

In summary, we successfully synthesized and characterized the Fe3O4@PTMS-AHNS MNPs, serving as an effective solid acid catalyst for the green, one-pot synthesis of polysubstituted pyridines. We meticulously optimized reaction parameters, finding that 25 mg of catalyst in a 1:2 V/V water/ethanol mixture under reflux yielded excellent results, and demonstrated the method’s broad applicability across various substituted aryl aldehydes, noting sensitivity to both electronic and steric effects. A key advantage of the Fe3O4@PTMS-AHNS catalyst is its exceptional reusability and recoverability, maintaining stability over at least five catalytic cycles with minimal efficiency loss, as confirmed by SEM analysis showing no structural degradation. This developed protocol offers a superior alternative to existing methods, providing higher yields, shorter reaction times, and greener conditions with its environmentally friendly water/ethanol solvent system and the added benefit of easy magnetic separation due to its heterogeneous nature.

Acknowledgments

Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2025R186), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Author contributions

Maha Abdallah Alnuwaiser: Conceptualization, Investigation, Methodology, Writing - original draft.Ishraga Galal Eldin: Investigation, Methodology.Mai Mousa Mahmoud Alhejoj: Conceptualization, Supervision, Resources.Ahmed Mohajja Alshammari: Software; Visualization, Writing - review & editing.Mohmed Ahmed Habib: Project administration, Investigation.Saad Alrashdi: Methodology, Writing - review & editing. Acknowledgments:Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2025R186), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Funding

There was no funding.

Data availability

The authors declare that all the data are available the data within the paper.

Declarations

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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