Skip to main content
NCBI home page
ACS Omega logoLink to ACS Omega
. 2026 Mar 11;11(11):17558–17575. doi: 10.1021/acsomega.5c11148

Sustainable One-Pot Synthesis of Dihydropyrimidinones Using a Bio-Waste-Derived Magnetic Sulfonated SBA-16/NiAl-LDO Catalyst

Pakin Noppawan †,‡,*, Kanyarat Saenthornsin †,‡, Sonchai Intachai §, Kanyaphat Torboon †,‡, Pareenat Waenthongkham †,‡, Andrew J Hunt ∥
PMCID: PMC13019263  PMID: 41908438

Abstract

This study presents the development of a novel magnetic heterogeneous catalyst derived from waste sugarcane bagasse ash for the efficient one-pot synthesis of dihydropyrimidinones via the Biginelli reaction. The catalyst combines mesoporous SBA-16 silica with NiAl-layered double oxides (LDO) and Fe3O4 nanoparticles, further functionalized with sulfonic acid groups to enhance surface acidity. The prepared SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst exhibited excellent structural properties, high surface area, and superparamagnetic behavior, enabling easy recovery and reuse. Under optimized green conditions (ethanol, 90 °C, 6 h), the catalyst delivered outstanding yields of up to 99% for various aromatic aldehydes, demonstrating superior performance compared to conventional silica-based and magnetic catalysts. Sustainability analysis, including green metrics such as Process Mass Intensity, E-factor, and Atom Economy, confirmed the process’s high efficiency and low environmental impact. The catalyst maintained high activity over multiple cycles with minimal efficiency loss, highlighting its potential for industrial applications with high turnover number (TON, 3,300) and turnover frequency (TOF, 550 h–1). This work introduces an innovative, biowaste-derived magnetic catalyst with excellent reusability and sustainability, offering a practical and environmentally friendly alternative for the synthesis of pharmaceutically valuable dihydropyrimidinones.

graphic file with name ao5c11148_0020.jpg

graphic file with name ao5c11148_0018.jpg

Introduction

Multicomponent reactions (MCRs) represent an efficient and sustainable strategy in organic synthesis, enabling the construction of structurally complex molecules through the one-pot condensation of three or more reactants. These reactions are widely recognized for their excellent atom economy, step economy, waste minimization, and ability to integrate diverse molecular fragments into a single scaffold. MCRs have found broad applications in the synthesis of pharmaceutically active compounds, biologically relevant scaffolds, and diversity-oriented libraries. Among them, the Biginelli reactionfirst reported by Pietro Biginelli in 1893remains a prototypical acid-catalyzed MCR involving the condensation of aldehydes, β-ketoesters, and (thio)­urea to afford 3,4-dihydropyrimidin-2­(1H)-ones (DHPMs). , These heterocycles exhibit a wide range of biological activities, including antiviral, anticancer, anti-inflammatory, antifungal, and antimalarial properties. − The efficiency and selectivity of the Biginelli reaction are strongly dependent on the nature of the catalyst. Early studies primarily employed homogeneous acid catalysts such as HCl, trifluoroacetic acid (TFA), ZnCl2, CuCl2, and LaCl3 due to their high intrinsic activity. − However, these systems suffer from inherent drawbacks, including difficult separation, lack of recyclability, corrosion issues, and the generation of environmentally undesirable acidic waste streams. These limitations have motivated extensive research into heterogeneous catalytic systems that combine high activity with facile recovery and reusability.

In heterogeneous catalysis, performance is governed not only by the nature of the active sites but also by the physicochemical properties of the support material, which influence active-site dispersion, mass-transfer efficiency, stability, and recyclability. Consequently, a wide range of catalyst supports has been explored, each offering distinct advantages and limitations. Metal oxide supports (e.g., Al2O3, TiO2, ZrO2, and MgO) are widely used owing to their thermal stability, mechanical robustness, and tunable acid–base properties. − Nevertheless, many metal oxides exhibit limited surface areas and suboptimal dispersion of active species, which can restrict catalytic efficiency in multicomponent reactions requiring rapid diffusion and multiple activation steps. Carbon-based materials, including activated carbon, graphene, and biomass-derived carbons, offer high surface area, electrical conductivity, and chemical tunability. − While attractive from a sustainability perspective, their hydrophobic nature and limited intrinsic acidity often necessitate extensive functionalization to achieve high activity in acid-catalyzed reactions. Metal–organic frameworks (MOFs) provide exceptionally high surface areas and well-defined pore architectures; , however, many MOFs suffer from insufficient hydrothermal and chemical stability under acidic or high-temperature conditions, limiting their applicability in demanding multicomponent reactions such as the Biginelli condensation. Layered double hydroxides (LDHs) and their calcined derivatives, layered double oxides (LDOs), represent another important class of heterogeneous catalysts. Upon calcination, LDHs transform into LDOs with increased surface area, abundant surface defects, and enhanced Lewis acidity, making them effective promoters for condensation reactions. − Despite these advantages, LDH/LDO materials alone often suffer from aggregation, limited mass transfer, and challenging recovery from reaction mixtures without additional structural support.

Mesoporous silica materials, such as MCM-41 and SBA-15, have therefore emerged as widely used catalyst supports due to their high surface areas, tunable pore sizes, chemical inertness, and ease of surface functionalization. − However, their one- or two-dimensional channel structures are susceptible to pore blocking and diffusion limitations in multicomponent reactions, as observed in silica-supported Biginelli and related condensations. In contrast, SBA-16 possesses a unique three-dimensional cubic (Im3m) cage-like mesostructure with interconnected pore entrances, which enables enhanced mass transport, reduced diffusion resistance, and improved resistance to structural degradation during repeated catalytic cycles. , These structural advantages promote uniform dispersion of active species and superior recyclability compared with SBA-15, MCM-41, and amorphous silica supports. , Despite its structural advantages, functionalized SBA-16 remains relatively underexplored in multicomponent catalysis due to the complexity of its synthesis and processing conditions. , Nevertheless, several studies have demonstrated the catalytic potential of SBA-16-based materials. For example, sulfonic-acid-functionalized SBA-16 (SBA-16/SO3H) has been applied in Kabachnik-Fields reactions for the synthesis of α-aminophosphonates, showing good catalytic activity, albeit using hazardous solvents such as dichloromethane. Similarly, Fe2O3–ZrO2/SBA-16 and Al-SBA-16 catalysts have been reported, but their preparation typically relies on tetraethyl orthosilicate (TEOS), raising concerns regarding cost, toxicity, and sustainability. , These limitations highlight the need for safer, low-cost silica sources and simplified synthesis strategies to improve the practicality and industrial viability of SBA-16-based catalysts.

Magnetic supports, particularly Fe3O4-based materials, have attracted increasing attention due to their facile separation using an external magnetic field, which minimizes catalyst loss and reduces energy-intensive filtration or centrifugation steps. − However, bare Fe3O4 nanoparticles typically exhibit low surface area and a strong tendency toward aggregation, necessitating their integration with high-surface-area supports to achieve optimal catalytic performance.

Herein, we report the development of a highly efficient magnetic heterogeneous catalyst by integrating sulfonated SBA-16 with NiAl-LDO and Fe3O4. In this composite system, SBA-16derived from industrial wasteprovides a robust three-dimensional mesoporous framework and Brønsted acidic −SO3H sites, NiAl-LDO contributes accessible Lewis acidic centers, and Fe3O4 enables facile magnetic recovery. This rational integration addresses the key limitations of individual catalyst classesnamely diffusion resistance, limited acidity, and poor recoverabilityresulting in a synergistic catalytic platform for the Biginelli reaction. The present design strategy combines catalytic efficiency, recyclability, and sustainability, offering a viable pathway toward greener multicomponent synthesis.

Experimental Procedures

Synthesis of NiAl-LDO from NiAl-LDH

NiAl-layered double hydroxide (NiAl-LDH) was synthesized through a coprecipitation approach, serving as the precursor for NiAl-layered double oxide (LDO). In this process, 0.030 mol of Ni2+ (M2+) and 0.010 mol of Al3+ (M3+) aqueous solutions were combined under vigorous magnetic stirring for 10 min. The pH of the resulting solution was gradually adjusted to approximately 9 by the slow addition of ammonia solution. The mixture was then sealed and maintained at 80 °C for 24 h to allow for complete precipitation. The formed solid was separated via centrifugation, washed repeatedly with deionized water until a neutral pH (∼7) was achieved, and subsequently dried at 80 °C for another 24 h to obtain NiAl-LDH. A portion of the prepared LDH was then calcined at 400 °C for 2 h to produce NiAl-LDO. The elemental composition was verified using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES), confirming that the Ni:Al molar ratio remained consistent with the target stoichiometry of 3:1.

Synthesis of SBA-16 and SBA-16-SO3H

Sugarcane bagasse ash (SCBA) was used as the silica source for the synthesis of SBA-16. The SCBA was obtained from Buriram Energy Co., Ltd. (BEC), a biomass power plant located in Buriram Province, Thailand. The preparation method followed our previously published procedure. In particular, 4.0 g of SCBA and 6.0 g of NaOH, at a weight ratio of 1.5:1, were mixed thoroughly to achieve uniformity. The mixture was then heated in a crucible at 550 °C under atmospheric pressure for 40 min. The fused product obtained was dissolved in 50 mL of deionized water to produce solution 1. In a separate step, 4.0 g of Pluronic F127 surfactant was dissolved in 120 mL of 2 M HCl at room temperature, followed by stirring until a uniform gel (solution 2) was formed. Solution 2 was then incrementally added to solution 1, and the resulting mixture was stirred gently at room temperature for 20 h. The solid product was collected by filtration, rinsed with deionized water, and dried at 80 °C for 4 h. Finally, calcination of the dried material was carried out at 550 °C in air for 6 h to remove the surfactant, resulting in the final SBA-16 material.

The incorporation of thiol (RSH) groups into SBA-16 was achieved through a batch reaction carried out in a 150 mL flask fitted with a stirrer, thermometer, and reflux condenser at 60 °C. In a standard process, 1.0 g of SBA-16 was dispersed in 30 mL of toluene, followed by the addition of 1.0 mL of 3-mercaptopropyltrimethoxysilane (MPTMS). The mixture was stirred continuously for 24 h to ensure complete functionalization. To oxidize the thiol groups, 30 mL of 30 wt % H2O2 solution was gradually added dropwise to the mixture under moderate stirring at room temperature over 24 h. The resulting solid was collected by filtration, thoroughly rinsed with deionized water, and dried at 80 °C for 4 h. This product was labeled as SBA-16-SO3H.

Synthesis of Fe3O4

Iron­(III) chloride (0.01 M, 2.7029 g) and ammonium iron­(II) sulfate (0.005 M, 1.9607 g) were dissolved in 20 mL of water. Sodium hydroxide (1.8 g in 20 mL of water) was added under stirring for 15 min. The precipitate was washed with water until pH 7, followed by ethanol, and dried at 80 °C for 20 h to obtain dark-brown magnetite.

Preparation of SBA-16-SO3H/NiAl-LDH/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4

Magnetic catalysts were preparation by accurately weighing SBA-16-SO3H, LDH, and Fe3O4 (1:1:1 by weight) and thoroughly grinding the components in a mortar to achieve a homogeneous mixture. A magnet was then employed to separate the magnetic catalyst from nonmagnetic residues, yielding the SBA-16-SO3H/NiAl-LDH/Fe3O4 catalyst. The SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst was synthesized using an identical procedure, with LDO substituted for LDH. Scheme illustrates the chemically explicit synthesis pathway of the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst, highlighting key structural transformations and surface functionalization steps. −

1. Chemically Explicit Stepwise Synthesis of the SBA-16-SO3H/NiAl-LDO/Fe3O4 Catalyst.

1

Open in a new tab

Catalyst Characterization

Fourier-transform infrared (FTIR) spectra were collected using a Bruker INVENIO-S spectrometer over the range of 400–4000 cm–1. X-ray diffraction (XRD) patterns were recorded with a Bruker D8 Advance diffractometer equipped with a Cu Kα radiation source (40 kV, 40 mA). Nitrogen adsorption–desorption isotherms were measured on a Micromeritics TriStar II Plus analyzer. The specific surface area was calculated by the Brunauer–Emmett–Teller (BET) method, and the pore size distribution was determined using the Barrett–Joyner–Halenda (BJH) method. Thermogravimetric analysis (TGA) was performed on an SDT Q600 thermal analyzer (TA Instruments, New Castle, DE, USA). Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS) images were obtained using a JEOL JSM-6010LV microscope. Transmission Electron Microscopy (TEM) images were captured with an FEI TECNAI G2 20 microscope. The magnetic properties of the materials were analyzed using a vibrating sample magnetometer (VSM, 8600 Series).

General Procedure for the Preparation of 3,4-Dihydropyrimidin-2­(1H)-ones

A mixture of aldehyde (5 mmol), β-ketoester or 1,3-diketone (7.5 mmol), urea (5 mmol), catalyst in varying amounts, and 4 mL of ethanol was stirred at different temperatures and times. The progress of the reaction was monitored by thin-layer chromatography (TLC) using dichloromethane/hexane (6:4) as the mobile phase. Upon completion, the catalyst was separated from the solution using an external magnet, and the solvent was evaporated to yield the solid product. The solid was washed with 10 mL of 50% ethanol in water and recrystallized from 5 mL of ethanol to obtain the pure product. The recovered catalyst was washed twice with 10 mL of hot ethanol and reused in subsequent reactions.

Results and Discussion

Catalyst Characterization: Fourier Transform Infrared (FT-IR) Spectroscopy

FTIR spectra of the catalysts SBA-16/NiAl-LDH/Fe3O4, SBA-16-SO3H/NiAl-LDH/Fe3O4, SBA-16/NiAl-LDO/Fe3O4, and SBA-16-SO3H/NiAl-LDO/Fe3O4 show several common features, including absorption bands at approximately 587 cm–1 and 630 cm–1, corresponding to Fe–O bonds in the Fe3O4 crystalline, as well as peaks related to hydroxyl (OH) groups, silanol (Si–OH) groups, and metal–oxygen (M-O) bonds. The spectra of SBA-16/NiAl-LDH/Fe3O4 and SBA-16-SO3H/NiAl-LDH/Fe3O4 exhibit distinct peaks at 3433 cm–1 (OH stretching), 1380 cm–1 (carbonate stretching), 992 cm–1 (Si–OH), 784 cm–1 (M–O stretching), 564 cm–1 (M–O bending), and 446 cm–1 (M–O bending), indicating the presence of NiAl-LDH. In contrast, the spectra of SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4 show the absence of carbonate-related peaks around 1380 cm–1 due to the calcination of NiAl-LDH to NiAl-LDO, with new absorption bands at 3447 cm–1 (OH from water), 1636 cm–1 (OH bending), and 804, 564, and 446 cm–1 (Ni–O and/or Al–O vibrations) confirming the transformation to NiAl-LDO. , The key difference in SBA-16-SO3H-containing catalysts is the presence of peaks at 930 cm–1 (S–O), 1425 cm–1 (SO), and 3000–3250 cm–1 (O–H bending of −SO3H), which confirm the successful incorporation of sulfonic acid groups into the silica framework, a feature absent in the SBA-16/NiAl-LDH/Fe3O4 and SBA-16/NiAl-LDO/Fe3O4 catalysts (Figure ).

1.

1

Open in a new tab

FTIR spectrum of SBA-16, SBA-16-SO3H, Fe3O4, NiAl-LDH, NiAl-LDO, SBA-16/NiAl-LDH/Fe3O4, SBA-16-SO3H/NiAl-LDH/Fe3O4, SBA-16/NiAl-LDO/Fe3O4, and SBA-16-SO3H/NiAl-LDO/Fe3O4.

Catalyst Characterization: X-ray Diffraction (XRD) Spectroscopy

Figure presents the small-angle X-ray diffraction (XRD) patterns of SBA-16. The material exhibits distinct diffraction peaks at 2θ = 0.97°, 1.25°, 1.38°, and 1.76°, which can be indexed to the (110), (200), (211), and (220) reflections of the cubic Im3m symmetry. These well-defined reflections confirm the preservation of the ordered cage-like mesoporous structure of SBA-16. The observed diffraction features are in good agreement with previously reported SBA-16 materials, further validating the successful synthesis of the mesostructured framework. − Figure presents the XRD patterns of the samples, including SBA-16, SBA-16-SO3H, Fe3O4, NiAl-LDH, NiAl-LDO, SBA-16/NiAl-LDH/Fe3O4, SBA-16-SO3H/NiAl-LDH/Fe3O4, SBA-16/NiAl-LDO/Fe3O4, and SBA-16-SO3H/NiAl-LDO/Fe3O4. The results indicate that the catalysts SBA-16/NiAl-LDH/Fe3O4, SBA-16-SO3H/NiAl-LDH/Fe3O4, SBA-16/NiAl-LDO/Fe3O4, and SBA-16-SO3H/NiAl-LDO/Fe3O4 exhibit diffraction peaks in identical positions, specifically at 2θ = 11.5°, 21.9°, 26.8°, 30.5°, 36.1°, 43.5°, 57.5°, and 63.1°. The peak at 2θ = 26.8° corresponds to the (111) plane (JCPDS card no 27–1404), confirming the presence of Si within the structure of SBA-16 and SBA-16-SO3H. The peaks at 2θ = 30.5°, 36.1°, 57.5°, and 63.1° correspond to the (220), (311), (400), (511) and (440) planes (JCPDS card no. 19–062), respectively, which are characteristic of Fe3O4. − For the SBA-16/NiAl-LDH/Fe3O4 and SBA-16-SO3H/NiAl-LDH/Fe3O4 catalysts, additional characteristic peaks are observed at 2θ = 11.5° and 21.9°, corresponding to the (003) and (006) planes of NiAl-LDH (JCPDS card no. 15–0087), confirming the successful synthesis of NiAl-LDH. In contrast, for the SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4 catalysts, contain NiAl-LDO after calcination. The characteristic peaks of NiAl-LDH including 2θ = 11.5° disappear, together with the appearance of new diffraction peaks corresponding to the (111), (200) and (220) which is consistent with NiO formation (JCPDS card no. 01–1239), indicating a complete transformation from NiAl-LDH to NiAl-LDO.

2.

2

Open in a new tab

Small-angle X-ray diffraction patterns of SBA-16.

3.

3

Open in a new tab

X-ray diffraction patterns of SBA-16, SBA-16-SO3H, Fe3O4, NiAl-LDH, NiAl-LDO, SBA-16/NiAl-LDH/Fe3O4, SBA-16-SO3H/NiAl-LDH/Fe3O4, SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4.

Catalyst Characterization: N2 Adsorption–Desorption Analysis

The BET analysis results for the synthesized mesoporous catalysts, presented in Table and Figure , confirm that all materials possess mesoporous characteristics, as evidenced by type IV nitrogen adsorption–desorption isotherms with a pronounced hysteresis loop in the relative pressure range of P/P 0 = 0.4–1. These findings are consistent with the IUPAC classification of mesoporous materials. The Fe3O4 sample exhibited a high surface area of 109.24 m2 g–1 and a total pore volume of 0.29 cm3 g–1, with nearly all the pore volume contributed by mesopores (99.87%) (Figure a). This structure is beneficial for diffusion and adsorption processes. In contrast, NiAl-LDH exhibited an undetectably low surface area, likely due to its dense lamellar structure, whereas the calcined form, NiAl-LDO (Figure b), showed a measurable surface area of 3.28 m2 g–1 and a small average pore size of 6.79 nm, indicating partial decomposition and porosity generation. After incorporating mesoporous silica (SBA-16), the SBA-16/NiAl-LDH/Fe3O4 composite showed a significantly increased surface area of 89.15 m2 g–1 and a large total pore volume of 0.31 cm3 g–1. The average pore size was also the largest among all samples (14.96 nm), reflecting a well-developed mesoporous network. Upon sulfonation, the SBA-16-SO3H/NiAl-LDH/Fe3O4 sample further increased in surface area (102.87 m2 g–1), though the total pore volume slightly decreased (0.28 cm3 g–1), and the average pore size reduced slightly to 13.44 nm. This may be attributed to partial pore blocking or surface condensation during the introduction of SO3H groups. Similarly, for the SBA-16/NiAl-LDO/Fe3O4 composite (Figure c), the surface area was relatively lower (63.81 m2 g–1), and after functionalization with SO3H (SBA-16-SO3H/NiAl-LDO/Fe3O4), the surface area slightly increased to 70.70 m2 g–1. Notably, the average pore size increased to 15.11 nm, the highest among all the samples, which suggests that the acid functionalization may have opened the pore channels or improved pore accessibility. In summary, the incorporation of SBA-16 significantly enhanced the surface area and mesoporosity of the composite catalysts, while sulfonation with SO3H groups contributed to further modifications of the textural properties. These structural enhancements are advantageous for catalytic applications where surface area and pore accessibility play critical roles. −

1. Results of BET Analysis for Catalysts.

data S BET (m2 g–1) S micro (m2 g–1) S meso (m2 g–1) V total (cm3 g–1) V micro (cm3 g–1) V meso (cm3 g–1) V micro /V total (%) V meso/V total (%) average pore size (nm)
Fe3O4 109.24 2.76 106.48 0.29 0.0004 0.29 0.13 99.87 11.15
NiAl-LDH       0.0005   0.0005   100 3.15
NiAl-LDO 3.28   3.28 0.0057   0.0057   100 6.79
SBA-16/NiAl-LDH/Fe3O4 89.15 0.29 88.87 0.31   0.31   100 14.96
SBA-16-SO3H/NiAl-LDH/Fe3O4 102.87 11.32 91.55 0.28 0.0051 0.27 1.84 98.16 13.44
SBA-16/NiAl-LDO/Fe3O4 63.81 2.91 60.90 0.14 0.0011 0.14 0.74 99.26 9.79
SBA-16-SO3H/NiAl-LDO/Fe3O4 70.70 1.76 68.94 0.25 0.0003 0.25 0.11 99.98 15.11
Open in a new tab

4.

4

Open in a new tab

N2 adsorption–desorption isotherm of (a) Fe3O4, (b) NiAl-LDO and (c) SBA-16/NiAl-LDO/Fe3O4, SBA-16-SO3H/NiAl-LDO/Fe3O4, SBA-16/NiAl-LDH/Fe3O4 and SBA-16-SO3H/NiAl-LDH/Fe3O4.

Catalyst Characterization: Thermal Analysis

Samples were heated from 40 to 800 °C at a rate of 20 °C min–1 under a nitrogen atmosphere. Figure illustrates the thermal behavior of the catalysts under a nitrogen atmosphere, showing the results for the following catalysts: SBA-16, SBA-16-SO3H, Fe3O4, NiAl-LDO, SBA-16/NiAl-LDO/Fe3O4, and SBA-16-SO3H/NiAl-LDO/Fe3O4. All the catalysts exhibit weight loss around 100 °C, which is attributed to moisture loss. The weight loss observed for SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4 in the range of 250–600 °C may result from various processes, such as the removal of residual hydroxyl (−OH) groups, decomposition of interlayer anions like carbonate (CO3 2–) or nitrate (NO3 –), and the reorganization of the mixed oxide (NiO-Al2O3) into a more stable phase. A notable feature observed in SBA-16-SO3H/NiAl-LDO/Fe3O4 is the significant weight loss in the range of 200–600 °C, which corresponds to the decomposition of sulfonic (−SO3H) groups, which is clearly seen by the DTG analysis. These findings confirm the successful incorporation of sulfonic groups into the catalyst structure, as evidenced by the thermal stability profile of SBA-16-SO3H. −

5.

5

Open in a new tab

TGA and DTG measurements for SBA-16, SBA-16-SO3H, Fe3O4, NiAl-LDO, SBA-16/NiAl-LDO/Fe3O4, SBA-16-SO3H/NiAl-LDO/Fe3O4.

Catalyst Characterization: Scanning Electron Microscopy (SEM)

Figure presents SEM images of SBA-16, SBA-16-SO3H, Fe3O4, NiAl-LDO, SBA-16/NiAl-LDO/Fe3O4, and SBA-16-SO3H/NiAl-LDO/Fe3O4. Under the applied synthesis conditions, SBA-16 and SBA-16-SO3H (Figure a,b) exhibit uniformly distributed and densely packed small particles, indicating a relatively compact structure with low porosity. In contrast, NiAl-LDO (Figure c) shows large, smooth-surfaced crystalline structures, reflecting the characteristics of calcined materials. Upon incorporation with SBA-16 and Fe3O4, both SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4 (Figure d,e) display surfaces composed of loosely aggregated small particles with discontinuous morphology, resulting in increased porosity. −

6.

6

Open in a new tab

SEM images of (a) SBA-16, (b) SBA-16-SO3H, (c) NiAl-LDO, (d) SBA-16/NiAl-LDO/Fe3O4, and (e) SBA-16-SO3H/NiAl-LDO/Fe3O4.

Catalyst Characterization: Transmission Electron Microscopy (TEM) with Energy Dispersive X-ray Spectroscopy (EDS)

The internal structure of the prepared materials was characterized using TEM-EDS. The TEM images of SBA-16/NiAl-LDH/Fe3O4 and SBA-16-SO3H/NiAl-LDH/Fe3O4 are shown in (Figure ), revealing that the Fe3O4 particles, which appear dark, are unevenly distributed within both materials. EDS analysis was performed to identify the elemental composition of these materials confirming the presence of Fe, C, Si, and O elements distributed evenly (Figure ). This supports the successful synthesis of both SBA-16/NiAl-LDH/Fe3O4 and SBA-16-SO3H/NiAl-LDH/Fe3O4. Notably, Fe, C, Si, and O are the major components in these materials as shown in Figure . The C element originates from the use of sugarcane bagasse ash in the synthesis of SBA-16, while Ni and Al are primarily associated with the layered double oxide (LDO) structure. Furthermore, the presence of sulfur (S) is exclusive to the SBA-16-SO3H/NiAl-LDH/Fe3O4 composite, confirming the incorporation of the −SO3H group, consistent with previous FTIR and XRD results. −

7.

7

Open in a new tab

TEM images at different magnifications of SBA-16/NiAl-LDO/Fe3O4 catalyst (a–c) and SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst (d–f).

8.

8

Open in a new tab

TEM-EDS images of (a) SBA-16/NiAl-LDH/Fe3O4 and (c) SBA-16-SO3H/NiAl-LDH/Fe3O4 and Elemental analysis of (b) SBA-16/NiAl-LDO/Fe3O4, and (d) SBA-16-SO3H/NiAl-LDO/Fe3O4.

Catalyst Characterization: Vibrating-Sample Magnetometer (VSM)

The magnetic properties of the materials were analyzed using a vibrating sample magnetometer (VSM, 8600 Series). The magnetic hysteresis loops of Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4 catalysts at room temperature are illustrated in Figure . Both catalysts exhibit superparamagnetic behavior, as evidenced by their narrow hysteresis curves. This characteristic is attributed to the distribution of Fe3O4 crystallites within their structure. The saturation magnetization value of the Fe3O4 catalyst is 57.18 emu/g, whereas the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst shows a significantly lower value of 19.91 emu g–1. The observed decrease in magnetic saturation can be ascribed to the incorporation of Fe3O4 into the SBA-16-SO3H/NiAl-LDO composite, where nonmagnetic components such as SBA-16 and LDO reduce the overall magnetic intensity. Despite the decrease in magnetization, the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst still exhibits favorable magnetic properties. This makes it suitable as a magnetically recoverable catalyst, facilitating efficient separation from the reaction products using an external magnetic field, thereby enhancing the recovery and reusability process. ,

9.

9

Open in a new tab

VSM analysis of Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4.

Catalyst Characterization: Ammonia Temperature-Programmed Desorption (NH3-TPD)

Figure shows the NH3-TPD profile of the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst. A dominant desorption peak centered around 150 °C is observed, which is attributed to weak to moderate Brønsted acid sites associated with surface sulfonic acid (SO3H) groups. In addition, a broader desorption feature extending above 200 °C is present. This high-temperature signal can be attributed to stronger acid sites and Lewis acidic centers (∼200 °C) originating from the NiAl-LDO component, as well as strong acid-NH3 interactions. Importantly, the onset of this high-temperature desorption region is also consistent with the thermal decomposition of SO3H groups, as evidenced by the TGA results, which show a corresponding weight-loss event above 200 °C. Similar acidity and thermal behavior has been reported for sulfonated SBA-16 materials derived from sugarcane bagasse ash and for NiAl-LDO catalysts. , The total acidity determined by NH3-TPD was 0.091 mmol/g, which exceeds the SO3H density obtained from acid–base titration (0.050 mmol g–1). This difference arises because NH3-TPD accounts for both Brønsted and Lewis acid sites, whereas titration selectively measures Brønsted acidity. These combined results confirm the successful introduction of sulfonic acid groups and the coexistence of Brønsted and Lewis acid sites in the composite catalyst, providing a comprehensive acidity profile relevant to its catalytic performance.

10.

10

Open in a new tab

NH3-TPD profile of the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst showing the distribution of acidic sites.

Catalyst Performance Evaluation: Catalyst Screening and Optimization of Reaction Conditions

Table summarizes the consolidated optimization of reaction parameters for the Biginelli reaction, including catalyst screening, catalyst loading, reaction temperature, and reaction time. All reactions were performed using aldehyde (5 mmol), β-ketoester (7.5 mmol), and urea (5 mmol) in ethanol under the specified conditions, and product yields refer to isolated yields.

2. Optimization of Reaction Parameters for the Biginelli Reaction.

entry catalyst temperature (°C) time (h) catalyst loading (wt %) solvent yield (%)
1 No catalyst 75 3 10 EtOH 33
2 Fe3O4 75 3 10 EtOH 39
3 SBA-16 75 3 10 EtOH 46
4 SBA-16-SO3H 75 3 10 EtOH 63
5 NiAl-LDH 75 3 10 EtOH 9
6 NiAl-LDH/Fe3O4 75 3 10 EtOH 33
7 SBA-16/NiAl-LDH/Fe3O4 75 3 10 EtOH 10
8 SBA-16-SO3H/NiAl-LDH/Fe3O4 75 3 10 EtOH 41
9 NiAl-LDO 75 3 10 EtOH 38
10 NiAl-LDO/Fe3O4 75 3 10 EtOH 41
11 SBA-16/NiAl-LDO/Fe3O4 75 3 10 EtOH 79
12 SBA-16-SO3H/NiAl-LDO/Fe3O4 75 3 10 EtOH 79
13 SBA-16/NiAl-LDO/Fe3O4 85 3 10 EtOH 79
14 SBA-16/NiAl-LDO/Fe3O4 90 3 10 EtOH 88
15 SBA-16/NiAl-LDO/Fe3O4 95 3 10 EtOH 91
16 SBA-16/NiAl-LDO/Fe3O4 105 3 10 EtOH 93
17 SBA-16-SO3H/NiAl-LDO/Fe3O4 85 3 10 EtOH 80
18 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 3 10 EtOH 91
19 SBA-16-SO3H/NiAl-LDO/Fe3O4 95 3 10 EtOH 94
20 SBA-16-SO3H/NiAl-LDO/Fe3O4 105 3 10 EtOH 95
21 SBA-16/NiAl-LDO/Fe3O4 90 4 10 EtOH 91
22 SBA-16/NiAl-LDO/Fe3O4 90 5 10 EtOH 93
23 SBA-16/NiAl-LDO/Fe3O4 90 6 10 EtOH 97
24 SBA-16/NiAl-LDO/Fe3O4 90 7 10 EtOH 98
25 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 4 10 EtOH 93
26 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 5 10 EtOH 97
27 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 6 10 EtOH 99
28 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 7 10 EtOH 99
29 SBA-16/NiAl-LDO/Fe3O4 90 6 2 EtOH 37
30 SBA-16/NiAl-LDO/Fe3O4 90 6 4 EtOH 66
31 SBA-16/NiAl-LDO/Fe3O4 90 6 6 EtOH 88
32 SBA-16/NiAl-LDO/Fe3O4 90 6 8 EtOH 88
33 SBA-16/NiAl-LDO/Fe3O4 90 6 12 EtOH 99
34 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 6 2 EtOH 56
35 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 6 4 EtOH 80
36 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 6 6 EtOH 85
37 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 6 8 EtOH 94
38 SBA-16-SO3H/NiAl-LDO/Fe3O4 90 6 12 EtOH 99
Open in a new tab

To evaluate the individual catalytic contributions, a comprehensive catalyst screening study was performed using 11 different catalysts (Scheme and Table , entries 1–12). Among the tested systems, SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4 (entries 11 and 12) exhibited the highest catalytic performance, each affording yield of approximately 79%. In contrast, catalysts lacking either sufficient Brønsted acidity or a cooperative Brønsted-Lewis acid framework generally resulted in significantly lower yields (≤63%). These results clearly demonstrate that the synergistic interaction among the mesoporous SBA-16 support, surface sulfonic acid groups, and Lewis acidic NiAl-LDO is critical for achieving high catalytic efficiency under the applied reaction conditions. It is noteworthy that SBA-16-SO3H alone afforded a moderate yield (63%) under the present conditions (Table , entry 4), which is lower than the yield reported for silica sulfuric acid catalysts in the literature. This difference can be attributed to the substantially lower Brønsted acid site density and catalyst loading employed in this work, as well as milder reaction conditions, reflecting a distinct catalytic regime that prioritizes controlled acidity and cooperative Brønsted-Lewis acid catalysis over high acid loading.

2. General Reaction Equation Employed for Catalyst Screening Studies in the Biginelli Reaction.

2

Open in a new tab

The influence of reaction temperature on product yield was subsequently investigated over the range of 75–105 °C (Table , entries 11–20). For both SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4, the yield increased progressively with temperature, from 79% at 75 °C to 88–91% at 90 °C (entries 14 and 18). Further increasing the temperature to 105 °C led to slightly higher yields of 93% and 95%, respectively (entries 16 and 20). However, considering energy efficiency and practical operation, 90 °C was selected as the optimal reaction temperature. The observed enhancement in yield with increasing temperature can be attributed to improved reactant diffusion, enhanced molecular collisions, and more effective activation of the catalytic sites.

The effect of reaction time was also examined for the two most active catalysts (Table , entries 11, 12, and 21–28). After 3 h, yields of 88% and 91% were obtained for SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4, respectively. Prolonging the reaction time resulted in a gradual increase in yield, reaching near-quantitative conversion after 6 h (entries 23 and 27). Extending the reaction beyond 6 h did not lead to significant further improvement. Therefore, a reaction time of 6 h was identified as optimal, ensuring efficient utilization of the catalyst active sites and complete conversion of reactants.

Catalyst loading was found to be another critical parameter influencing reaction efficiency (Table , entries 11, 12, and 29–38). For SBA-16/NiAl-LDO/Fe3O4, increasing the catalyst loading from 2 to 12 wt % led to a substantial increase in yield from 37% to 99% (entries 29–33). Further increases in catalyst loading did not result in noticeable yield enhancement, indicating that 12 wt % is sufficient for this system. In the case of SBA-16-SO3H/NiAl-LDO/Fe3O4, increasing the catalyst loading from 2 to 10 wt % significantly improved the yield from 56% to 99% (entries 34 and 12), while higher loadings did not provide additional benefits. Accordingly, 10 wt % was identified as the optimal catalyst loading for this catalyst.

Overall, the optimal conditions for the Biginelli reaction were established as a reaction temperature of 90 °C, a reaction time of 6 h, and a catalyst loading of 10 wt % using SBA-16-SO3H/NiAl-LDO/Fe3O4. These conditions provide excellent yields while maintaining efficient catalyst utilization. Furthermore, a 10-fold gram-scale Biginelli reaction (50 mmol scale-up) proceeded smoothly under the optimized conditions, affording the target product in 99% yield, comparable to that obtained on the small scale. Reaction progress at different time intervals was monitored by TLC, as shown in Figure S51.

Catalyst Performance Evaluation: Substrate Scopes for Biginelli Reaction

The catalytic performance of SBA-16/NiAl-LDO/Fe3O4 and its sulfonated counterpart, SBA-16-SO3H/NiAl-LDO/Fe3O4, was evaluated in the Biginelli reaction under optimized conditions (EtOH, 90 °C, 6 h) (Table  ), with particular emphasis on the electronic effects of substituents on aromatic aldehydes. In this study, the substrate scope was deliberately limited to para-substituted aromatic aldehydes to systematically assess electronic effects while minimizing steric influences; extension to ortho- and meta-substituted aldehydes will be explored in future work. As shown in the experimental matrix, aldehydes bearing electron-withdrawing groups such as NO2 (entries 5, 10, 15) and Cl (entries 3, 8, 13) generally afforded high product yields, ranging from 87% to 99% across both catalytic systems, confirming their favorable influence on enhancing electrophilic reactivity. In contrast, substrates containing electron-donating groups (e.g., OCH3, CH3; entries 2, 4, 7, 12, 13) exhibited a marked decline in yields, especially in the absence of sulfonic acid functionality. For example, entry 2 (R1 = OCH3) resulted in a yield of only 42% with SBA-16-SO3H/NiAl-LDO/Fe3O4, and negligible conversion with the nonsulfonated catalyst, corroborating previous findings that electron-rich aromatics hinder the condensation process. Notably, the incorporation of the SO3H group on SBA-16 significantly enhanced catalytic efficiency; for instance, in entry 11, the yield increased from 39% to 98%, with similarly high yields in entries 6 and 9 (95–99%). The lowest yields were observed when both the aldehyde and diketone components contained electron-donating substituents (entry 12:22–32%), indicating an additive deactivation effect. Overall, these results demonstrate that both the electronic nature of the reactants and the surface acidity of the catalyst are critical factors in optimizing the one-pot synthesis of dihydropyrimidinones via the Biginelli reaction. ,

3. Substrate Scope for the Biginelli Reaction in the Presence of by SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4 .

graphic file with name ao5c11148_0017.jpg

      melting point (°C)
 %yield
entry R1 R2 observed reported SBA-16/NiAl-LDO/Fe3O4 SBA-16-SO3H/NiAl-LDO/Fe3O4
1 H OCH3 196–198 202–205 97 99
2 OCH3 OCH3 185–187 186–188 0 42
3 Cl OCH3 204–206 204–206 71 87
4 CH3 OCH3 214–216 213–215 87 99
5 NO2 OCH3 235–237 235–237 97 99
6 H OCH2CH3 202–204 202–204 95 99
7 OCH3 OCH2CH3 205–207 206–207 0 44
8 Cl OCH2CH3 213–215 215–216 74 89
9 CH3 OCH2CH3 204–206 205–206 92 99
10 NO2 OCH2CH3 205–207 207–208 97 99
11 H CH3 236–238 236–237 39 98
12 OCH3 CH3 170–172 168–170 22 32
13 Cl CH3 214–216 215–216 76 92
14 CH3 CH3 224–226 227–228 93 99
15 NO2 CH3 235–237 234–235 90 98
Open in a new tab
a

Conditions: aldehyde (5 mmol), β-diketonates (7.5 mmol), urea (5 mmol), catalysts (10 wt %), 90 °C, 6 h.

Heterogeneity Test

To confirm the true heterogeneous nature and stability of the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst, hot filtration and metal leaching experiments were carried out under the optimized reaction conditions. The hot filtration test was performed following established procedures reported in the literature. , During the model Biginelli condensation of benzaldehyde, methyl acetoacetate, and urea, the reaction was intentionally interrupted after 1 h, corresponding to approximately 64% conversion. At this stage, the solid catalyst was rapidly removed from the hot reaction mixture using an external magnetic field and washed with a minimal amount of hot ethanol. The resulting clear filtrate, now free of solid catalyst, was then allowed to react further under identical conditions. Only a marginal increase in yield was observed, reaching 65% after 6 h, indicating that the reaction did not proceed appreciably in the absence of the solid catalyst (Figure ). This result confirms that the catalytic activity originates predominantly from the heterogeneous catalyst surface rather than from leached active species. In addition, possible metal leaching from the catalyst was investigated after completion of the catalytic reaction. The recovered catalyst-containing reaction mixture was washed with hot ethanol (20 mL), and the combined washing solution was concentrated by rotary evaporation and subsequently digested with 40% (v/v) HNO3 prior to analysis. Anodic stripping square wave voltammetry (SWASV) was employed as a sensitive method for detecting trace amounts of nickel and iron in the filtrate. Electrochemical measurements were performed using a screen-printed carbon electrode. During the preconcentration step, metal ions were reduced and deposited onto the electrode surface at −1.5 V for 60 s, followed by anodic stripping via potential scanning from −1.3 to +0.75 V at a scan rate of 125 mV s–1, with a step potential of 5 mV, an amplitude of 20 mV, and a frequency of 25 Hz. Standard solutions of iron and nickel (10 μg mL–1) exhibited well-defined anodic stripping peaks at −0.68 V and −0.03 V, respectively, in agreement with reported values. , In contrast, no corresponding anodic peaks were detected in the washing solution obtained from the catalytic reaction (Figure ), indicating that any leached metal species were below the detection limit of 10 μg mL–1. Taken together, the hot filtration and electrochemical leaching studies provide strong evidence for the true heterogeneous behavior, excellent stability, and resistance to metal leaching of the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst under the applied reaction conditions.

11.

11

Open in a new tab

Hot filtration test for the Biginelli reaction catalyzed by SBA-16-SO3H/NiAl-LDO/Fe3O4 under the optimized conditions.

12.

12

Open in a new tab

Square-wave voltammograms of 10 μg mL–1 standard iron and nickel and the washing solution.

Proposed Reaction Mechanism and Role of the Catalyst

Figure illustrates the proposed catalytic mechanism for the synthesis of dihydropyrimidinones (DHPMs) over the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst. The mechanism is adapted from well-established Brønsted-Lewis acid catalyzed Biginelli pathways reported in the literature and reflects the cooperative roles of sulfonic acid and metal-oxide Lewis acid sites. , Initially, the Brønsted acidic −SO3H groups protonate the aldehyde carbonyl, increasing its electrophilicity and facilitating condensation with the 1,3-dicarbonyl compound to form intermediate (c). Subsequent dehydration leads to the α,β-unsaturated enone intermediate (d). In parallel, Lewis acidic sites associated with the NiAl-LDO component coordinate to the carbonyl oxygen atoms of the β-ketoester, stabilizing the enolized form and promoting its interaction with the activated aldehyde species. The nucleophilic amino group of urea then attacks the activated enone intermediate to generate intermediate (f). Intramolecular nucleophilic attack of the second amino group onto the adjacent carbonyl group results in cyclization to form the six-membered dihydropyrimidinone framework (g). Final dehydration, assisted by Lewis acid sites, affords the desired DHPM product. In this cooperative catalytic system, Brønsted acidity accelerates carbonyl activation and dehydration steps, while Lewis acidic NiAl-LDO sites enhance electrophilicity through coordination, lower activation barriers for cyclization, and stabilize key intermediates.

13.

13

Open in a new tab

Proposed cooperative Brønsted–Lewis acid catalyzed mechanism for DHPM synthesis over SBA-16-SO3H/NiAl-LDO/Fe3O4, highlighting the roles of −SO3H groups and NiAl-LDO Lewis acid sites in carbonyl activation, cyclization, and dehydration.

Comparison of the Current Magnetic Silica-Based Catalyst with Previously Reported Silica-Based Catalysts for the Biginelli Reaction

The comparative data in Table  clearly demonstrates that the magnetic silica-based catalysts developed in this work, SBA-16/NiAl-LDO/Fe3O4 and SBA-16-SO3H/NiAl-LDO/Fe3O4, derived from waste sugarcane bagasse ash, exhibit superior catalytic performance for the Biginelli reaction compared to other silica-based and magnetic catalysts reported in the literature. Notably, both catalysts achieved excellent yields (97% and 99%, respectively) under mild, green conditions (EtOH, 90 °C, 6 h) using only 0.03 g of catalyst, which is comparable or even lower than the amounts required for other systems. For example, although Fe3O4@SiO2/H2PO3 and Fe3O4@SiO2–IL/[Mo6O19] catalysts also afforded high yields (97–99% and 90%, respectively), these systems typically rely on more complex or costly modifiers, often require inert conditions, or lack the added sustainability benefit of being derived from agro-industrial waste. Furthermore, other reported catalysts such as Fe3O4@SBA-15 and LDH-based systems showed lower yields (85–88%) or required shorter times at higher temperatures, but without the multifunctionality and recyclability demonstrated by the SBA-16/NiAl-LDO/Fe3O4 catalysts. Importantly, the introduction of the sulfonic acid group (SO3H) further enhanced the catalytic activity by increasing surface acidity, thus boosting the reaction efficiency, especially for substrates with challenging electron-donating substituents. The turnover frequency (TOF) represents the instantaneous catalytic efficiency, while the turnover number (TON) indicates the maximum number of times a catalyst can be utilized before deactivation. TOF is defined as (yield/time) per mole of catalyst, and TON is calculated as (yield) per mole of catalyst. Based on the Brønsted acid site density (−SO3H) determined by acid–base titration (0.05 mmol g–1), the turnover number (TON) and turnover frequency (TOF) of the SBA-16-SO3H/NiAl-LDO/Fe3O4 catalyst were calculated to be 3300 and 550 h–1, respectively. These values highlight the high catalytic efficiency of the heterogeneous system and are markedly higher than those reported for comparable catalysts. These results clearly demonstrate that the catalyst is both highly robust, capable of sustaining numerous catalytic cycles, and highly active, efficiently converting substrate to product per unit time per active site. Overall, these findings highlight that the innovative combination of magnetic properties, hierarchical mesoporosity, tunable acidity, and sustainable biowaste sourcing make these newly developed catalysts highly competitive and environmentally attractive alternatives for the efficient one-pot synthesis of dihydropyrimidinones.

4. Comparative Account of Catalysts for the Optimized Biginelli Reaction.

entry catalyst solvent catalyst (g) temperature (°C) time yield (%) TON TOF (h–1) refs
1 Silica sulfuric acid EtOH 0.23 (30 mol %) 60 6 h 92 3.1 0.5
2 Fe3O4@SBA-15 EtOH 0.05 90 6 h 85 n.a. n.a.
3 LDH EtOH 0.0005 (75 mol %) 75 4 h 88 1.2 0.3
4 Mg/Al-LDH   0.03 90 40 min 88 n.a. n.a.
5 Fe3O4@SiO2/H2PO3 EtOH 0.05 70 2 h 97–99 n.a. n.a.
6 Fe3O4@SiO2–IL/[Mo6O19]   0.01 (0.25 mol %) 65 40 min 90 360 537.3
7 Fe3O4@SiO2/ZnCl2   0.05 110 25 min 90 n.a. n.a.
8 Fe–Co–V/Zeolite and Fe–Co–Mo/Zeolite   0.001 80 25–55 min 82 n.a. n.a.
9 SBA-16-SO3H/NiAl-LDO/Fe3O4 EtOH 0.03 (0.03 mol %) 90 6 h 99 3300 550 this work
Open in a new tab
a

The acid density of the catalyst was determined by an acid–base titration method, giving a value of 0.05 mmol g–1. In this procedure, 0.05 g of the catalyst was dispersed in 30 mL of 2 M aqueous NaCl solution and subjected to ultrasonic treatment for 30 min at room temperature. The supernatant solution was then titrated with 0.005 M NaOH to quantify the acid sites. Not applicable (n.a.): calculation could not be performed due to the absence of catalytic site data.

Reusability of Catalyst

Under optimal conditions, the magnetic catalyst exhibited excellent recyclability, maintaining a high yield of 98% even after three consecutive cycles (Figure ). Although a decline in yield was observed in the fourth cycle, the catalyst retained an impressive efficiency of 76.34% after five cycles, demonstrating its sustained catalytic performance over multiple uses. To further enhance its recyclability, future modifications could involve the direct synthesis of magnetically active LDH/LDO, which may improve its long-term usability. These findings underscore the superior durability and efficiency of the magnetic catalyst even after multiple reaction cycles. Despite a gradual decrease in catalytic efficiency beyond the third cycle, the magnetic catalyst outperformed those previously studied by Mekki which exhibited significant efficiency losses upon repeated use. In contrast, the magnetic catalyst demonstrated ease of separation from the reaction mixture, enhanced stability, and strong potential as a sustainable catalytic system. The recyclability of the catalyst was further investigated by extending the reuse study up to ten consecutive cycles under the optimized Biginelli reaction conditions. As shown in Figure S46, the catalyst maintained excellent catalytic activity during the first three cycles, affording yields of 99%, 98%, and 97%, respectively. A noticeable decrease in activity was observed from the fourth cycle onward, with yields declining to 77% and 74% in the fourth and fifth cycles, followed by a more pronounced reduction in subsequent runs. After ten cycles, the yield decreased to 17%, indicating the onset of catalyst deactivation. The gradual decrease in catalytic activity observed upon repeated reuse of the catalyst can be rationalized by changes in surface acidity rather than structural degradation of the support. To elucidate this behavior, the recovered catalyst after cycles 1, 3, and 5 was systematically characterized. Acid–base titration revealed that the fresh catalyst possessed an SO3H density of 0.050 mmol g–1, which remained largely preserved after cycle 1 (0.048 mmol g–1, 99% yield) and cycle 3 (0.047 mmol g–1, 98% yield). In contrast, a pronounced reduction in acidity was observed after cycle 5, where the SO3H density decreased to 0.031 mmol g–1, coinciding with a significant drop in catalytic yield (76%) (Table S2). These findings indicate that high catalytic performance is closely correlated with the availability of Brønsted acid sites. This trend is further supported by TEM-EDS analysis, which showed a substantial decrease in sulfur content from 0.34 wt % after cycle 1 to 0.13 wt % after cycle 5 (Figure S48). The combined acidity and compositional analyses suggest that the observed loss of activity originates primarily from partial leaching or degradation of surface sulfonic acid groups during repeated reaction and recovery steps, rather than collapse of the SBA-16 mesostructure. Overall, the catalyst exhibits good stability over the initial cycles, while the gradual depletion of acid sites defines the practical recyclability limit under the applied reaction conditions. Nevertheless, the catalyst demonstrates a clearly defined operational stability window of up to three highly efficient cycles. These findings highlight both the robustness of the catalyst under repeated use and the importance of structural optimization for further enhancing long-term recyclability.

14.

14

Open in a new tab

Reusability of catalyst on Biginelli reaction. Reaction conditions: the reactions were carried out with methyl acetoacetate (7.5 mmol), benzaldehyde (5 mmol), urea (5 mmol) and SBA-16-SO3H/NiAl-LDO/Fe3O4 (10 wt %) in ethanol at 90 °C for 6 h.

In comparison with our previously reported SCBA-derived SBA-16/SO3H catalyst, which featured solely sulfonic acid sites on a mesoporous silica framework, the present SBA-16-SO3H/NiAl-LDO/Fe3O4 composite exhibits enhanced acidity, magnetic recoverability, and greater structural robustness. The incorporation of NiAl-LDO nanoparticles introduces additional Lewis acid centers while preventing pore collapse during repeated catalytic cycles. Whereas the earlier SBA-16/SO3H achieved a surface area of 207 m2 g–1 and a 99% yield in the Biginelli reaction at 105 °C for 7 h (10 wt % catalyst), the current SBA-16-SO3H/NiAl-LDO/Fe3O4 system attains comparable yields under milder conditions and demonstrates superior recyclability owing to its magnetic component, which simplifies catalyst recovery. Both catalysts share sustainability advantages derived from agro-waste precursors; however, the present hybrid design further advances this concept by integrating waste valorization with multifunctionality and improved reusability.

Sustainability Analysis of Biginelli Synthesis

In this study, a thorough sustainability analysis of the Biginelli reaction catalyzed by SBA-16-SO3H/NiAl-LDO/Fe3O4 was performed using standard green chemistry metrics, including the Process Mass Intensity (PMI) and E-factor (Table ). , These metrics assess the process’s efficiency and environmental footprint. PMI indicates the overall material efficiency, while the E-factor evaluates waste production, with an ideal process striving for a PMI near 1 and an E-factor as close to 0 as possible. The results from this study showed that many of the reactions, particularly those resulting in products 5, 10, and 15, achieved PMI and E-factor values close to these ideal targets, highlighting the efficiency of the method. The Atom Economy (AE) value remained consistently high for all substrates, mostly exceeding 86%, while product yields were above 85% in nearly every case, with some reactions even achieving 99% yields. This demonstrates excellent synthetic efficiency. The Water Intensity (WI) and Solvent Intensity (SI) were both moderate, reflecting a relatively low consumption of auxiliary materials throughout the process. The data reveals a wide range of performance across different products, but with several achieving high atom economy, excellent yields, and favorable PMI and E-factor values. Notably, products 5, 10, and 15 exhibited the lowest PMI and E-factor values, indicating that the method is both efficient and environmentally friendly.

5. Sustainability Metrics for Biginelli Syntheses Catalyzed by SBA-16-SO3H/NiAl-LDO/Fe3O4 .

product PMI (g g–1) E-Factor (g g–1) AE (%) WI (g g–1) SI (g g–1) yield (%)
1 14.59 13.59 87 4.11 10.35 99
2 30.77 29.77 88 8.59 13.89 42
3 14.65 13.65 89 4.08 10.33 87
4 13.84 12.84 88 3.88 10.17 99
5 12.48 11.48 89 3.47 9.85 99
6 13.90 12.90 88 3.89 10.18 99
7 28.15 27.15 89 7.81 13.28 44
8 13.80 12.80 89 3.83 10.13 89
9 13.19 12.19 89 3.68 10.01 99
10 11.45 10.45 88 3.16 9.61 99
11 15.64 14.64 94 4.43 10.61 98
12 42.87 41.87 86 12.05 16.62 32
13 14.57 13.57 88 4.09 10.34 92
14 14.72 13.72 88 4.16 10.39 99
15 12.56 11.56 87 3.52 9.88 98
Open in a new tab

As in our previous SCBA-derived SBA-16/SO3H study, the present system demonstrates strong alignment with green chemistry metrics, exhibiting a low E-factor and favorable PMI values. The DOZN-based sustainability assessment of the earlier catalyst yielded an overall score of 75/100, confirming a greener process compared with conventional TEOS-based synthesis. Building upon that foundation, the magnetic SBA-16-SO3H/NiAl-LDO/Fe3O4 composite offers additional advantages by eliminating filtration steps and reducing solvent consumption during catalyst recovery, thereby further enhancing its life-cycle performance. Collectively, these improvements illustrate how the present catalyst advances our previous design toward a more energy- and resource-efficient platform.

Conclusion

In summary, this study demonstrates the successful design of a novel, magnetically recoverable heterogeneous catalyst, SBA-16-SO3H/NiAl-LDO/Fe3O4, synthesized from waste sugarcane bagasse ash. By integrating mesoporous SBA-16 silica, NiAl-layered double oxide, and Fe3O4 nanoparticles, the catalyst combines high surface area, hierarchical porosity, tunable acidity, and superparamagnetic properties within a single multifunctional framework. Sulfonic acid functionalization further enhances surface acidity, improving catalytic efficiency, particularly for reactions involving electron-deficient aromatic aldehydes. This catalyst enables an efficient one-pot Biginelli reaction under mild, green conditions (ethanol, 90 °C, 6 h), achieving yields up to 99% across a broad substrate scope. Compared with previously reported silica-based and magnetic catalysts, this biowaste-derived system provides superior yields, simpler separation, and avoids complex synthesis routes or expensive modifiers. The magnetic property also facilitates straightforward recovery and reuse, maintaining high activity over multiple cycles with minimal loss, confirming excellent operational stability and reusability. Comprehensive sustainability assessments, including Process Mass Intensity, E-factor, Atom Economy, and solvent usage, reveal high material efficiency and minimal waste generation. This work builds upon our earlier SCBA-derived SBA-16/SO3H catalyst by developing a bifunctional, magnetically separable SBA-16-SO3H/NiAl-LDO/Fe3O4 system that offers comparable activity with enhanced durability and recyclability. The synergistic interaction between sulfonic acid and NiAl-LDO components delivers high turnover and simpler reusability, advancing the design toward energy-efficient, circular, and sustainable catalytic processes. Overall, this research provides a promising strategy for transforming agricultural waste into cost-effective, environmentally benign catalysts for scalable and sustainable chemical manufacturing.

Supplementary Material

ao5c11148_si_001.docx (18.2MB, docx)

Acknowledgments

This research project was financially supported by Thailand Science Research and Innovation (TSRI). The authors would like to thank the Department of Chemistry, Faculty of Science, Mahasarakham University, for providing facility support.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.5c11148.

  • Experimental procedures, 1H NMR spectra and green metric evaluation (DOCX)

The authors declare no competing financial interest.

References

  1. Dömling A., Wang W., Wang K.. Chemistry and Biology of Multicomponent Reactions. Chem. Rev. 2012;112(6):3083–3135. doi: 10.1021/cr100233r. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Nagarajaiah H., Mukhopadhyay A., Moorthy J. N.. Biginelli reaction: an overview. Tetrahedron Lett. 2016;57(46):5135–5149. doi: 10.1016/j.tetlet.2016.09.047. [DOI] [Google Scholar]
  3. Kappe C. O., Roschger P.. Synthesis and reactions of “biginelli-compounds”. Part I. J. Heterocycl. Chem. 1989;26(1):55–64. doi: 10.1002/jhet.5570260112. [DOI] [Google Scholar]
  4. Bosica G., Cachia F., De Nittis R., Mariotti N.. Efficient One-Pot Synthesis of 3,4-Dihydropyrimidin-2­(1H)-ones via a Three-Component Biginelli Reaction. Molecules. 2021;26(13):3753. doi: 10.3390/molecules26123753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Mokale S. N., Shinde S. S., Elgire R. D., Sangshetti J. N., Shinde D. B.. Synthesis and anti-inflammatory activity of some 3-(4,6-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl) propanoic acid derivatives. Bioorg. Med. Chem. Lett. 2010;20(13):4424–4426. doi: 10.1016/j.bmcl.2010.06.058. [DOI] [PubMed] [Google Scholar]
  6. Kumar B. C., Reddy K. R. V., Fasiulla, Shridhara A. M.. Synthesis, Characterization and Antimicrobial Activity of Some Novel 2,3-Disubstituted Thiazolidin-4-One Derivatives. J. Chem. Pharm. Res. 2013;5(9):1–6. [Google Scholar]
  7. Bais J., Benedetti F., Berti F., Cerminara I., Drioli S., Funicello M., Regini G., Vidali M., Felluga F.. One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues. Molecules. 2020;25(20):4152. doi: 10.3390/molecules25184152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. de Fátima Â., Braga T. C., da S Neto L., Terra B. S., Oliveira B. G. F., da Silva D. L., Modolo L. V.. A mini-review on Biginelli adducts with notable pharmacological properties. J. Adv. Res. 2015;6(3):363–373. doi: 10.1016/j.jare.2014.10.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rogerio K. R., Carvalho L. J. M., Domingues L. H. P., Neves B. J., Moreira Filho J. T., Castro R. N., Bianco C. Jr., Daniel-Ribeiro C. T., Andrade C. H., Graebin C. S.. Synthesis and molecular modelling studies of pyrimidinones and pyrrolo­[3,4-d]-pyrimidinodiones as new antiplasmodial compounds. Mem. Inst. Oswaldo Cruz. 2018;113:170452. doi: 10.1590/0074-02760170452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Aslanoğlu F., Esvet A., Mehmet S., Anıl B.. Studies on Reactions of Pyrimidine Compounds: Synthesis and Reactions of 5-Benzoyl-4,6-Diphenyl-1,2,3,4-Tetrahydro-2-Thioxopyrimidine. Phosphorus, Sulfur, Silicon Relat. Elem. 2007;182:1589–1597. doi: 10.1080/10426500701263554. [DOI] [Google Scholar]
  11. Singh K., Singh J., Deb P. K., Singh H.. An expedient protocol of the Biginelli dihydropyrimidine synthesis using carbonyl equivalents. Tetrahedron. 1999;55:12873–12880. doi: 10.1016/S0040-4020(99)00760-7. [DOI] [Google Scholar]
  12. Reddy C. V., Mahesh M., Raju P. V. K., Babu T. R., Reddy V. V. N.. Zirconium­(IV) chloride catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2­(1H)-ones. Tetrahedron Lett. 2002;43:2657–2659. doi: 10.1016/s0040-4039(02)00280-0. [DOI] [Google Scholar]
  13. Prajapati D., Gohain M., Sandhu J. S.. A Novel Cu-catalysed Three-component One-pot Synthesis of Dihydropyrimidin-2­(1H)-ones Using Microwaves under Solvent-free Conditions. Synlett. 2004;2004:235–238. doi: 10.1055/s-2003-43374. [DOI] [Google Scholar]
  14. Lu J., Bai Y., Wang Z., Yang B., Ma H.. One-pot synthesis of 3,4-dihydropyrimidin-2­(1H)-ones using lanthanum chloride as a catalyst. Tetrahedron Lett. 2000;41:9075–9078. doi: 10.1016/s0040-4039(00)01645-2. [DOI] [Google Scholar]
  15. Jayarathna R., Javaid R., Lauterbach J.. Understanding the role of metal oxide support in ruthenium-based catalysts for ammonia synthesis via interpretable machine learning. J. Catal. 2025;447:116136. doi: 10.1016/j.jcat.2025.116136. [DOI] [Google Scholar]
  16. State R.-N., Morosan M.-A., Cretu L., Straca A.-I., Vasile A., Bratan V., Culita D., Atkinson I., Balint I., Papa F.. The Effect of the Metal Oxide as the Support for Silver Nanoparticles on the Catalytic Activity for Ammonia Ozonation. Catalysis. 2025;15:104. doi: 10.3390/catal15020104. [DOI] [Google Scholar]
  17. Rivera-Guasco R., López-Benítez A., Guevara-Lara A.. Ni-W Catalysts Supported on TiO2-Al2O3 for Efficient Green Diesel Production: “Standard” vs “Keggin” Comparison. ACS Omega. 2025;10:4276–4290. doi: 10.1021/acsomega.4c05634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Al-Fatesh A. S., Bamatraf N. A., Alreshaidan S. B., Abu-Dahrieh J. K., Patel N., Ibrahim A. A., Fakeeha A. H., bin Jumah A., Kumar R.. Cost-Effective Single-Step Synthesis of Metal Oxide-Supported Ni Catalyst for H2-Production Through Dry Reforming of Methane. Arab. J. Sci. Eng. 2024;49:8031–8047. doi: 10.1007/s13369-023-08576-0. [DOI] [Google Scholar]
  19. Valero-Romero M. J., Rodríguez-Cano M. Á., Palomo J., Rodríguez-Mirasol J., Cordero T.. Carbon-Based Materials as Catalyst Supports for Fischer–Tropsch Synthesis: A Review. Front. Mater. 2021;7:617432. doi: 10.3389/fmats.2020.617432. [DOI] [Google Scholar]
  20. Wang W., Wang Y., Kong X., Ning H., Wu M.. Carbon-based material for CO2 catalytic conversion applications. Carbon Future. 2024;1:9200016. doi: 10.26599/CF.2024.9200016. [DOI] [Google Scholar]
  21. Lam E., Luong J. H. T.. Carbon Materials as Catalyst Supports and Catalysts in the Transformation of Biomass to Fuels and Chemicals. ACS Catal. 2014;4:3393–3410. doi: 10.1021/cs5008393. [DOI] [Google Scholar]
  22. Sadakiyo M.. Support effects of metal–organic frameworks in heterogeneous catalysis. Nanoscale. 2022;14:3398–3406. doi: 10.1039/D1NR07659K. [DOI] [PubMed] [Google Scholar]
  23. Mussa N.-S., Toshtay K., Dumeignil F.. Recent developments in the field of MOF-based catalytic systems: A review. Appl. Catal., A. 2025;708:120555. doi: 10.1016/j.apcata.2025.120555. [DOI] [Google Scholar]
  24. Sun T., Wang X., Zhang J., Wang L., Song X., Huo P., Liu X.. A Short Review of Layered Double Oxide-Based Catalysts for NH3-SCR: Synthesis and NOx Removal. Catalysis. 2024;14:755. doi: 10.3390/catal14110755. [DOI] [Google Scholar]
  25. Feng J., He Y., Liu Y., Du Y., Li D.. Supported catalysts based on layered double hydroxides for catalytic oxidation and hydrogenation: general functionality and promising application prospects. Chem. Soc. Rev. 2015;44:5291–5319. doi: 10.1039/C5CS00268K. [DOI] [PubMed] [Google Scholar]
  26. Abd El-Monaem E. M., Elshishini H. M., Bakr S. S., El-Aqapa H. G., Hosny M., Andaluri G., El-Subruiti G. M., Omer A. M., Eltaweil A. S.. A comprehensive review on LDH-based catalysts to activate persulfates for the degradation of organic pollutants. npj Clean Water. 2023;6:34. doi: 10.1038/s41545-023-00245-x. [DOI] [Google Scholar]
  27. Shinde P. S., Suryawanshi P. S., Patil K. K., Belekar V. M., Sankpal S. A., Delekar S. D., Jadhav S. A.. A brief overview of recent progress in porous silica as catalyst supports. J. Compos. Sci. 2021;5:75. doi: 10.3390/jcs5030075. [DOI] [Google Scholar]
  28. Besoluk S., Kucukislamoglu M., Nebioglu M., Zengin M., Arslan M.. Solvent-free synthesis of dihydropyrimidinones catalyzed by alumina sulfuric acid at room temperature. J. Iran. Chem. Soc. 2008;5:62–66. doi: 10.1007/BF03245816. [DOI] [Google Scholar]
  29. Wei Y., Yang W., Yang Z.. An excellent universal catalyst support- mesoporous silica: Preparation, modification and applications in energy-related reactions. Int. J. Hydrogen Energy. 2022;47:9537–9565. doi: 10.1016/j.ijhydene.2022.01.048. [DOI] [Google Scholar]
  30. Shinde P. S., Suryawanshi P. S., Patil K. K., Belekar V. M., Sankpal S. A., Delekar S. D., Jadhav S. A.. A Brief Overview of Recent Progress in Porous Silica as Catalyst Supports. J. Compos. Sci. 2021;5:75. doi: 10.3390/jcs5030075. [DOI] [Google Scholar]
  31. Choudhary V. R., Tillu V. H., Narkhede V. S., Borate H. B., Wakharkar R. D.. Microwave assisted solvent-free synthesis of dihydropyrimidinones by Biginelli reaction over Si-MCM-41 supported FeCl3 catalyst. Catal. Commun. 2003;4:449–453. doi: 10.1016/S1566-7367(03)00111-0. [DOI] [Google Scholar]
  32. Ma Z., Yamg H., Qin Y., Hao Y., Li G.. Palladium nanoparticles confined in the nanocages of SBA-16: Enhanced recyclability for the aerobic oxidation of alcohols in water. J. Mol. Catal. A: Chem. 2010;331:78–85. doi: 10.1016/j.molcata.2010.08.006. [DOI] [Google Scholar]
  33. Cao Z., Du P., Duan A., Guo R., Zhao Z., Zhang H. L., Zheng P., Xu C., Chen Z.. Synthesis of mesoporous materials SBA-16 with different morphologies and their application in dibenzothiophene hydrodesulfurization. Chem. Eng. Sci. 2016;155:141–152. doi: 10.1016/j.ces.2016.08.001. [DOI] [Google Scholar]
  34. Lakshmidevi J., Vakati V., Naidu B. R., Raghavender M., Krishna Rao K. S. V., Venkateswarlu K.. Pd­(5%)-KIT-6, Pd(5%)-SBA-15 and Pd(5%)-SBA-16 catalysts in water extract of pomegranate ash: A case study in heterogenization of Suzuki-Miyaura reaction under external base and ligand free conditions. Sustainable Chem. Pharm. 2021;19:100371. doi: 10.1016/j.scp.2020.100371. [DOI] [Google Scholar]
  35. Tella J. O., Adekoya J. A., Ajanaku K. O.. Mesoporous silica nanocarriers as drug delivery systems for anti-tubercular agents: a review. R. Soc. Open Sci. 2022;9:220013. doi: 10.1098/rsos.220013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sakamoto Y., Díaz I., Terasaki O., Zhao D., Pérez-Pariente J., Kim J. M., Stucky G. D.. Three-Dimensional Cubic Mesoporous Structures of SBA-12 and Related Materials by Electron Crystallography. J. Phys. Chem. B. 2002;106:3118–3123. doi: 10.1021/jp014094q. [DOI] [Google Scholar]
  37. Boza A. F., Kupfer V. L., Oliveira A. R., Radovanovic E., Rinaldi A. W., Meneguin J. G., Domingues N. L. C., Moisés M. P., Favaro S. L. S.. Synthesis of α-aminophosphonates using a mesoporous silica catalyst produced from sugarcane bagasse ash. RSC Adv. 2016;6:23981–23986. doi: 10.1039/C5RA23233C. [DOI] [Google Scholar]
  38. Manimaran S., Pandurangan A., Govindasamy G.. Green synthesis of spherical mesoporous SBA-16 and its supported Fe2O3- ZrO2 catalyst for selective acetalization of glycerol to dioxolane as biofuel additive. J. Environ. Chem. Eng. 2023;11:109476. doi: 10.1016/j.jece.2023.109476. [DOI] [Google Scholar]
  39. Gallo J. M. R., Bisio C., Marchese L., Pastore H. O.. A zeolite-based vapor phase adsorptive desulfurization process for naphtha. Microporous Mesoporous Mater. 2011;145:124–130. doi: 10.1016/j.micromeso.2011.01.009. [DOI] [Google Scholar]
  40. Basumatary S. F., Das B., Das B. K., Hoque M., Brahma S., Basumatary B., Patir K., Selvaraj M., Rokhum S. L., Basumatary S.. Recent advances in magnetic solid catalysts: Synthesis, stabilization and application in cleaner production of biodiesel. Energy Nexus. 2024;15:100318. doi: 10.1016/j.nexus.2024.100318. [DOI] [Google Scholar]
  41. Govan J., Gun’ko Y. K.. Recent Advances in the Application of Magnetic Nanoparticles as a Support for Homogeneous Catalysts. Nanomaterials. 2014;4:222–241. doi: 10.3390/nano4020222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lim C. W., Lee I. S.. Magnetically recyclable nanocatalyst systems for the organic reactions. Nano Today. 2010;5:412–434. doi: 10.1016/j.nantod.2010.08.008. [DOI] [Google Scholar]
  43. Sead F. F., Jain V., Kumar A., Rekha M. M., Kundlas M., Gupta S., Kumari M., Kazemi M., Javahershenas R.. Magnetically recoverable catalysts for e multicomponent synthesis of organosulfur compounds. RSC Adv. 2025;15:3928–3953. doi: 10.1039/D4RA08769K. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Intachai S., Sumanatrakul P., Chaiburi C., Pewhom A., Nuengmatcha P., Khaorapapong N.. Green and facile assembly of LDO, AC, FeOOH and Fe3O4 as multifunctional composite catalyst for efficient biodiesel production and dye degradation. Fuel. 2024;371:132041. doi: 10.1016/j.fuel.2024.132041. [DOI] [Google Scholar]
  45. Saenthornsin K., Hunt P. J., Limtragool O., Noppawan P.. Mesoporous SBA-16/SO3H from waste sugarcane bagasse ash for efficient Biginelli reactions. Sci. Rep. 2025;15:15738. doi: 10.1038/s41598-025-99670-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wu K., Ye Q., Wang L., Meng F., Dai H.. Polyethyleneimine-modified layered double hydroxide/SBA-15 composites: A novel kind of highly efficient CO2 adsorbents. Appl. Clay Sci. 2022;229:106660. doi: 10.1016/j.clay.2022.106660. [DOI] [Google Scholar]
  47. Dhaneswara D., Marito H. S., Fatriansyah J. F., Sofyan N., Adhika D. R., Suhariadi I.. Spherical SBA-16 particles synthesized from rice husk ash and corn cob ash for efficient organic dye adsorbent. J. Cleaner Prod. 2022;357:131974. doi: 10.1016/j.jclepro.2022.131974. [DOI] [Google Scholar]
  48. Niakan M., Kargar P. G., Maleki B., Zabibah R. S., Daryapeima M., Ashrafi S. S., Zhou S.. Ternary AgFe2O4/SBA-16/SO3H Heterojunction Photocatalyst for the Sustainable Production of 5-Hydroxymethylfurfural under Mild Conditions. Langmuir. 2025;41:13220–13232. doi: 10.1021/acs.langmuir.5c00894. [DOI] [PubMed] [Google Scholar]
  49. Eftekhar M., Khosravi I.. CoII immobilized on aminated mesoporous SBA-16 (SBA-16/ GPTMS-NH2–CoII): a highly efficient mesostructured catalyst for the C–O bond formation under solvent-free conditions. J. Porous Mater. 2023;30:1255–1272. doi: 10.1007/s10934-022-01414-y. [DOI] [Google Scholar]
  50. Hosseinzadeh R., Mavaji M., Moradi I.. Synthesis and Characterization of Fe3O4@SiO2@MgAl-LDH@Au.Pd as an Efficient and Magnetically Recyclable Catalyst for Reduction of 4-Nitrophenol and Suzuki Coupling Reactions. Arab. J. Sci. Eng. 2023;48:7525–7541. doi: 10.1007/s13369-022-07543-5. [DOI] [Google Scholar]
  51. Nalbandian L., Patrikiadou E., Zaspalis V., Patrikidou A., Hatzidaki E., Papandreou C.. Magnetic Nanoparticles in Medical Diagnostic Applications: Synthesis, Characterization and Proteins Conjugation. Curr. Nanosci. 2016;12:455–468. doi: 10.2174/1573413712666151210230002. [DOI] [Google Scholar]
  52. Karnopp J. C. F., Cardoso T. F. A., Gonçalves D. A., Carollo A. R. H., de Castro G. R., Duarte A. P., Martines M. A. U.. Preparation of the rutin-SBA-16 drug delivery system. J. Biomater. Nanobiotechnol. 2020;11:1–13. doi: 10.4236/jbnb.2020.111001. [DOI] [Google Scholar]
  53. Sarkar S. M., Ali M., Rahman M. L., Yusoff M.. Preparation of mesoporous SBA-16 silica-supported biscinchona alkaloid ligand for the asymmetric dihydroxylation of olefins. J. Nanomater. 2014;2014:123680. doi: 10.1155/2014/123680. [DOI] [Google Scholar]
  54. Vanichvattanadecha C., Singhapong W., Jaroenworaluck A.. Different sources of silicon precursors influencing on surface characteristics and pore morphologies of mesoporous silica nanoparticles. Appl. Surf. Sci. 2020;513:145568. doi: 10.1016/j.apsusc.2020.145568. [DOI] [Google Scholar]
  55. Ghorbani F., Kamari S.. Core–shell magnetic nanocomposite of Fe3O4@SiO2@NH2 as an efficient and highly recyclable adsorbent of methyl red dye from aqueous environments. Environ. Technol. Innov. 2019;14:100333. doi: 10.1016/j.eti.2019.100333. [DOI] [Google Scholar]
  56. Yan W., Li Y., Zeng J., Bao W., Zhao H., Li J., Gunawan P., Yu F.. Silica-Decorated NiAl-Layered Double Oxide for Enhanced CO/CO2 Methanation Performance. Nanomaterials. 2022;12:3041. doi: 10.3390/nano12173041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Irzaman, Irmansyah, Aisyah S., Har N. P., Aminullah. Effect of Different Hydrothermal Temperatures on the Properties on Nano-Silica (SiO2) of Rice Husk. Int. J. Renew. Energy Dev. 2022;11:640–646. doi: 10.14710/ijred.2022.43904. [DOI] [Google Scholar]
  58. Hu F., Cui E., Liu H., Wu J., Dai Y., Yu G.. Layered Bi2MoO6/LDH hetero-structured composites with enhanced visible light photocatalytic activity. J. Mater. Sci.: Mater. Electron. 2019;30:2572–2584. doi: 10.1007/s10854-018-0532-9. [DOI] [Google Scholar]
  59. Hu X., Li P., Zhang X., Yu B., Lv C., Zeng N., Luo J., Zhang Z., Song J., Liu Y.. Ni-Based Catalyst Derived from NiAl Layered Double Hydroxide for Vapor Phase Catalytic Exchange between Hydrogen and Water. Nanomaterials. 2019;9:1688. doi: 10.3390/nano9121688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Thommes M., Kaneko K., Neimark A. V., Olivier J. P., Rodriguez-Reinoso F., Rouquerol J., Sing K. S. W.. Physisorption of gases, with special reference to the evaluation of surface area and pore size distribution (IUPAC Technical Report) Pure Appl. Chem. 2015;87:1051–1069. doi: 10.1515/pac-2014-1117. [DOI] [Google Scholar]
  61. Akopyan A. V., Shlenova A. O., Polikarpova P. D., Vutolkina A. V.. High-Performance Heterogeneous Oxidative Desulfurization Catalyst with Brønsted Acid Sites. Pet. Chem. 2022;62:636–642. doi: 10.1134/S0965544122040053. [DOI] [Google Scholar]
  62. Wang C., Li K., Ji P.. Using taurine to increase mesopores in Ce-based metal–organic framework for enhancing the production of 5-hydroxymethylfurfural and 5-ethoxymethylfurfural from fructose. J. Chem. Technol. Biotechnol. 2021;96:163–171. doi: 10.1002/jctb.6522. [DOI] [Google Scholar]
  63. Cardinale A. M., Carbone C., Consani S., Fortunato M., Parodi N.. Layered Double Hydroxides for Remediation of Industrial Wastewater from a Galvanic Plant. Crystals. 2020;10:443. doi: 10.3390/cryst10060443. [DOI] [Google Scholar]
  64. He Q., Lu Y., Peng Q., Chen W., Fan G., Chai B., Song G.. Synthesis of 5-hydroxymethylfurfural from fructose catalyzed by sulfonated carbon-based solid acid. Biomass Convers. Biorefin. 2023;13:9195–9203. doi: 10.1007/s13399-021-01847-6. [DOI] [Google Scholar]
  65. Song G., Wang Q., Yang L., Liao D., Li S.. Oxidative Dehydrogenation of Ethane with CO2 over Mo/LDO Catalyst: The Active Species of Mo Controlled by LDO. Catalysts. 2022;12:493. doi: 10.3390/catal12050493. [DOI] [Google Scholar]
  66. Vanichvattanadecha C., Jaroenworaluck A., Henpraserttae P., Wimuktiwan P.. Synthesis of Highly Ordered Mesoporous Silica (SBA-16) to Support Titania (TiO2) Nanoparticles for Enhancing the Degradation of Diuron Herbicide. Silicon. 2024;16:5907–5919. doi: 10.1007/s12633-024-03124-3. [DOI] [Google Scholar]
  67. Tronto, J. ; Bordonal, A. C. ; Naal, Z. ; Valim, J. . Materials Science – Advanced Topics; Mastai, Y. , Ed.; IntechOpen: London, 2013. 10.5772/54803. [DOI] [Google Scholar]
  68. Zeynizadeh B., Gilanizadeh M.. Green and highly efficient approach for the reductive coupling of nitroarenes to azoxyarenes using the new mesoporous Fe3O4@SiO2@Co–Zr–Sb catalyst. Res. Chem. Intermed. 2020;46:2969–2984. doi: 10.1007/s11164-020-04126-7. [DOI] [Google Scholar]
  69. Yu L., Xia A., Hao Y., Li W., He X., Xing C., Shang Z., Zhang Y.. COF-SiO2@Fe3O4 Composite for Magnetic Solid-Phase Extraction of Pyrethroid Pesticides in Vegetables. Molecules. 2024;29:2311. doi: 10.3390/molecules29102311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Singh P., Mishra S., Sahoo A., Patra S.. A magnetically retrievable mixed-valent Fe3O4@SiO2/Pd0/PdII nanocomposite exhibiting facile tandem Suzuki coupling/transfer hydrogenation reaction. Sci. Rep. 2021;11:9305. doi: 10.1038/s41598-021-88528-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Prasad C., Tang H., Liu W.. Magnetic Fe3O4 based layered double hydroxides (LDHs) nanocomposites (Fe3O4/LDHs): recent review of progress in synthesis, properties and applications. J. Nanostruct. Chem. 2018;8:393–412. doi: 10.1007/s40097-018-0289-y. [DOI] [Google Scholar]
  72. Mirbagheri R., Elhamifar D., Shaker M.. Yolk–shell structured magnetic mesoporous silica: a novel and highly efficient adsorbent for removal of methylene blue. Sci. Rep. 2021;11:23259. doi: 10.1038/s41598-021-02699-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Mahmud N., Benamor A., Nasser M. S., Ba-Abbad M. M., El-Naas M. H., Mohammad A. W.. Effective Heterogeneous Fenton-Like degradation of Malachite Green Dye Using the Core-Shell Fe3O4@SiO2 Nano-Catalyst. ChemistrySelect. 2021;6:865–875. doi: 10.1002/slct.202003937. [DOI] [Google Scholar]
  74. Yang X., Geng F., Yang Z., Rezayan A., Xu C. C., Wu D., Zhang Y.. Efficient metal-acid bifunctional catalysts derived from NiAl-LDO for the reductive catalytic fractionation of lignocellulose into phenolic monomers. ACS Sustainable Chem. Eng. 2024;12:13816–13825. doi: 10.1021/acssuschemeng.4c03808. [DOI] [Google Scholar]
  75. Salehi P., Dabiri M., Zolfigol M. A., Fard M. A. B.. Silica sulfuric acid: an efficient and reusable catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2­(1H)-ones. Tetrahedron Lett. 2003;44:2889–2891. doi: 10.1016/S0040-4039(03)00436-2. [DOI] [Google Scholar]
  76. Shah S. I. A., Kostiuk L. W., Kresta S. M.. The Effects of Mixing, Reaction Rates, and Stoichiometry on Yield for Mixing Sensitive ReactionsPart I: Model Development. Int. J. Chem. Eng. 2012;2012:750162. doi: 10.1155/2012/750162. [DOI] [Google Scholar]
  77. Jadhav C. K., Nipate A. S., Chate A. V., Songire V. D., Patil A. P., Gill C. H.. Efficient Rapid Access to Biginelli for the Multicomponent Synthesis of 1,2,3,4-Tetrahydropyrimidines in Room-Temperature Diisopropyl Ethyl Ammonium Acetate. ACS Omega. 2019;4:22313–22324. doi: 10.1021/acsomega.9b02286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Zheng S., Jian Y., Xu S., Wu Y., Sun H., Zhang G., Zhang W., Gao Z.. N-Donor ligand activation of titanocene for the Biginelli reaction via the imine mechanism. RSC Adv. 2018;8:8657–8661. doi: 10.1039/C8RA01208C. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Nemati F., Alizadeh S. G.. Bi-SO3H Functionalized Ionic Liquid Based on DABCO: New and Efficient Catalyst for Facile Synthesis of Dihydropyrimidinones. J. Chem. 2013;2013:235818. doi: 10.1155/2013/235818. [DOI] [Google Scholar]
  80. Khabazzadeh H., Kermani E. T., Jazinizadeh T.. An efficient synthesis of 3,4-dihydropyrimidin-2­(1H)-ones catalyzed by molten [Et3NH]­[HSO4] Arab. J. Chem. 2012;5:485–488. doi: 10.1016/j.arabjc.2010.09.015. [DOI] [Google Scholar]
  81. Kumar A., Maurya R.. Synthesis of 3,4-dihydropyrimidin-2­(1H)-ones using Ziegler–Natta catalyst system under solvent free conditions. J. Mol. Catal. A: Chem. 2007;272:53–56. doi: 10.1016/j.molcata.2007.03.026. [DOI] [Google Scholar]
  82. Harsh S., Kumar S., Sharma R., Kumar Y., Kumar R.. Chlorophyll triggered one-pot synthesis of 3,4-dihydropyrimidin-2­(1H)-ones via photo induced electron transfer reaction. Arab. J. Chem. 2020;13:4720–4730. doi: 10.1016/j.arabjc.2019.11.002. [DOI] [Google Scholar]
  83. Huseynzada A., Mori M., Meneghetti F., Israyilova A., Guney E., Sayin K., Chiarelli L. R., Demiralp M., Hasanova U., Abbasov V.. Crystal Structure, Hirshfeld Surface Analysis, In-Silico and Antimycotic Investigations of Methyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyrimidine-5-carboxylate. Crystals. 2023;13:52. doi: 10.3390/cryst13010052. [DOI] [Google Scholar]
  84. Abdolahi S., Soleiman-Beigi M.. Design of natural asphalt sulfamic acid (NA-NHSO3H) as a scalable natural asphalt-derived heterogeneous Brønsted acid to catalyze multicomponent reactions meeting green chemistry goals. Heliyon. 2025;11:e41492. doi: 10.1016/j.heliyon.2024.e41492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Nazifi M., Saeidian H., Taheri S.. Efficient Synthesis of 3,4-Dihydropyrimidin-2­(1H)-ones Catalyzed by a Cd-Based Covalent Organic Framework Under Solvent-Free Conditions. Chem. Methodol. 2024;8:490–506. doi: 10.48309/CHEMM.2024.464210.1806. [DOI] [Google Scholar]
  86. Patel M. M., Kapadia M. A., Joshi J. D.. Thermal and catalytic aspects of Ln­(III) polymer–metal complexes. Polym. Int. 2009;58:728–737. doi: 10.1002/pi.2584. [DOI] [Google Scholar]
  87. Dilmaghani K. A., Zeynizadeh B., Amirpoor M.. Ultrasound-Mediated Synthesis of 3,4-Dihydropyrimidin-2-(1H)-Ones (or Thiones) with NaHSO4·H2O. Phosphorus, Sulfur, Silicon. 2013;188:1634–1642. doi: 10.1080/10426507.2013.777725. [DOI] [Google Scholar]
  88. Slimi H., Moussaoui Y., ben Salem R.. Synthesis of 3,4-dihydropyrimidin-2­(1H)-ones/thiones via Biginelli reaction promoted by bismuth­(III)­nitrate or PPh3 without solvent. Arab. J. Chem. 2016;9:S510–S514. doi: 10.1016/j.arabjc.2011.06.010. [DOI] [Google Scholar]
  89. Devarajan N., Saravanakumar N., Suresh P.. Comparison of Catalytic Behaviors of Brønsted Versus Lewis Acidic MOFs in Synthesis of 2,4,5- Trisubstituted Imidazoles. Appl. Organomet. Chem. 2025;39:e70031. doi: 10.1002/aoc.70031. [DOI] [Google Scholar]
  90. Jafari F., Moeinpour F., Mohseni-Shahri F. S.. Minute-scale, solvent-free microwave-assisted three-component synthesis of naphtho­[1,2-e]­[1,3]­oxazin-3-ones catalyzed by a recyclable Brønsted-Lewis acidic COF. Results Chem. 2026;19:102940. doi: 10.1016/j.rechem.2025.102940. [DOI] [Google Scholar]
  91. Oza R., Shah N., Patel S.. Nickel Recovery from Spent Ni/Al2O3 Catalysts Using Nitric Acid Solution. Asian J. Water Environ. Pollut. 2011;8:51–58. doi: 10.3233/AJW-2011-8_3_08. [DOI] [Google Scholar]
  92. Scheers N., Andlid T., Alminger M., Sandberg A.-S.. Determination of Fe2+ and Fe3+ in Aqueous Solutions Containing Food Chelators by Differential Pulse Anodic Stripping Voltammetry. Electroanalysis. 2010;22:1090–1096. doi: 10.1002/elan.200900533. [DOI] [Google Scholar]
  93. Dewi G. C., Levin O.. Analysis of Nickel­(II) in Water Medium using Electrochemical Techniques. Chem. Mater. 2023;2:24–29. doi: 10.56425/cma.v2i1.49. [DOI] [Google Scholar]
  94. Noppawan P., Waenthongkham P., Torboon K., Ngernyen Y., Nijpanich S., Laokul P., Hunt A. J.. Sustainable corncob-derived sulfonated carbon catalysts for recyclable biginelli reactions in palm oil. Environ. Technol. Innov. 2026;41:104691. doi: 10.1016/j.eti.2025.104691. [DOI] [Google Scholar]
  95. Ramos L. M., de Leon y Tobio A. Y. P., dos Santos M. R., de Oliveira H. C. B., Gomes A. F., Gozzo F. C., de Oliveira A. L., Neto B. A. D.. Mechanistic Studies on Lewis Acid Catalyzed Biginelli Reactions in Ionic Liquids: Evidence for the Reactive Intermediates and the Role of the Reagents. J. Org. Chem. 2012;77:10184–10193. doi: 10.1021/jo301806n. [DOI] [PubMed] [Google Scholar]
  96. Kozuch S., Martin J. M. L.. Turning Over” Definitions in Catalytic Cycles. ACS Catal. 2012;2:2787–2794. doi: 10.1021/cs3005264. [DOI] [Google Scholar]
  97. Hemmati S., Yousefi M., Salehi M. H., Amiri M., Hekmati M.. Cu­(I)-anchored polyvinyl alcohol coated-magnetic nanoparticles as heterogeneous nanocatalyst in Ullmann-type C–N coupling reactions. Appl. Organomet. Chem. 2020;34:e5653. doi: 10.1002/aoc.5611. [DOI] [Google Scholar]
  98. Mondal J., Sen T., Bhaumik A.. Fe3O4@mesoporous SBA-15: a robust and magnetically recoverable catalyst for one-pot synthesis of 3,4-dihydropyrimidin-2­(1H)-ones via the Biginelli reaction. Dalton Trans. 2012;41:6173–6181. doi: 10.1039/c2dt30106g. [DOI] [PubMed] [Google Scholar]
  99. Ghotkar N. S., Berad B. N.. Biginelli synthesis of 3,4-dihydropyrimidin-2­(1H)-one using Layered Double Hydroxide (LDH) as a eco-friendly catalyst. Der Phar. Chem. 2015;7:167–172. [Google Scholar]
  100. Dib M., Ouchetto H., Akhramez S.. Preparation of Mg/Al-layered double hydroxide and its application in the synthesis of 3,4-dihydropyrimidin-2­(1H)-ones. J. Chem. Pharm. Res. 2018;10:106–116. [Google Scholar]
  101. Pirhadi L., Alana R., Soleimani E.. PO3H2-Functionalized Fe3O4@SiO2 Core–Shell as an Efficient and Magnetic Nanocatalyst for the Preparation of Dihydropyrimidinones via Biginelli Condensation. Polycycl. Aromat. Compd. 2022;42:4374–4385. doi: 10.1080/10406638.2021.1891104. [DOI] [Google Scholar]
  102. Kargar S., Elhamifar D., Zarnegaryan A.. Core–shell structured Fe3O4@SiO2-supported IL/[Mo6O19]: A novel and magnetically recoverable nanocatalyst for the preparation of biologically active dihydropyrimidinones. J. Phys. Chem. Solids. 2020;146:109601. doi: 10.1016/j.jpcs.2020.109601. [DOI] [Google Scholar]
  103. Maleki B., Heshmatollah A., Hengameh A., Reza T., Mofrad A. V.. One-Pot Synthesis of Polyhydroquinolines Catalyzed by ZnCl2 Supported on Nano Fe3O4@SiO2 . Org. Prep. Proced. Int. 2019;51:301–309. doi: 10.1080/00304948.2019.1600132. [DOI] [Google Scholar]
  104. Abadi S. Z. Y., Mohammadi M., Tavakkoli H.. Tri Oxometallic Zeolite Composite Nanostructures: New and Efficient Catalyst for Solvent Free Synthesis of Bis (Dihydropyrimidinone) Derivatives. J. Inorg. Organomet. Polym. Mater. 2021;31:2949–2958. doi: 10.1007/s10904-021-01905-6. [DOI] [Google Scholar]
  105. Mekki S., Laichi Y., Benourrad F., Lagha N., Chebout R., Bachari K., Saidi-Besbes S.. Copper triazole complex supported on Fe3O4@SiO2 nanoparticles as eco-friendly nanocatalysts in solvent-free Biginelli reaction. Appl. Organomet. Chem. 2023;37:e7103. doi: 10.1002/aoc.7103. [DOI] [Google Scholar]
  106. Augé J.. A new rationale of reaction metrics for green chemistry. Mathematical expression of the environmental impact factor of chemical processes. Green Chem. 2008;10:225–231. doi: 10.1039/B711274B. [DOI] [Google Scholar]
  107. Phan T. V. T., Gallardo C., Mane J.. GREEN MOTION: a new and easy to use green chemistry metric from laboratories to industry. Green Chem. 2015;17:2846–2852. doi: 10.1039/C4GC02169J. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao5c11148_si_001.docx (18.2MB, docx)

Articles from ACS Omega are provided here courtesy of American Chemical Society

RESOURCES