Magnetic BiFeO3 nanoparticles: a robust and efficient nanocatalyst for the green one-pot three-component synthesis of highly substituted 3,4-dihydropyrimidine-2(1H)-one/thione derivatives | Scientific Reports

Scientific Reports volume 14, Article number: 22201 (2024) Cite this article

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In this research, magnetic bismuth ferrite nanoparticles (BFO MNPs) were prepared through a convenient method and characterized. The structure and morphological characteristics of the prepared nanomaterial were confirmed through analyses using Fourier-transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), elemental mapping, powder X-ray diffraction (XRD), N2 adsorption–desorption isotherms and vibrating sample magnetometry (VSM) techniques. The obtained magnetic BFO nanomaterial was investigated, as a heterogeneous Lewis acid, in three component synthesis of 3,4-dihydropyrimidin-2 (1H)-ones/thiones (DHPMs/DHPMTs). It was found that the BFO MNPs exhibit remarkable efficacy in the synthesis of various DHPMs as well as their thione analogues. It is noteworthy that this research features low catalyst loading, good to excellent yields, environmentally friendly conditions, short reaction time, simple and straightforward work-up, and the reusability of the catalyst, distinguishing it from other recently reported protocols. Additionally, the structure of the DHPMs/DHPMTs was confirmed through 1H NMR, FTIR, and melting point analyses. This environmentally-benign methodology demonstrates the potential of the catalyst for more sustainable and efficient practices in green chemistry.

The synthesis of nitrogen-containing 3,4-dihydropyrimidine-2(1H)-one/thione compounds (DHPMs/DHPMTs) commenced several years ago, driven by the recognition of the 3,4-dihydropyrimidinone skeleton in compounds with diverse biological properties, corrosion inhibition, etc1,2,3. Beyond their structural characteristics, nitrogen-containing heterocycles serve as essential building blocks in the synthesis of various biologically active compounds. These compounds exemplify the significant intersection of structure and function within the broader scope of medicinal chemistry and drug design, making them essential components4,5,6,7,8,9,10. While some initial progresses have been made, there is still a need for further exploration and expansion of their synthetic process, thus justifying continued investigation. Indeed, heterocyclic compounds occupy a crucial and indispensable domain within the field of chemistry2,3,4,5,6,7. Their fundamental role as key compounds has a significant impact on various scientific and applied fields8. Notably, a significant number of medicinal and naturally occurring compounds possessing biological activity contain inherent heterocyclic structures9. These compounds act as essential scaffolds in drug discovery and development, playing a crucial role in the pharmaceutical industry. The diverse and complex structures of heterocyclic compounds enhance their versatility, making them essential components in the synthesis of novel therapeutic agents10. Recognizing the pivotal role of heterocyclic compounds sheds light on their profound influence in advancing both theoretical understanding and practical applications in the field of chemistry11.

The versatility of DHPMs/DHPMTs stems from the ability to modify their chemical structure and subsequent enhancing of their pharmacological properties and therapeutic potential (Fig. 1). For example, (S)-L-771688 (Fig. 1A), a compound derived from the DHPMs/DHPMTs structure, has been studied as an α1a-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia (BPH)5,6,7. In addition to BPH treatment, DHPMs/DHPMTs compounds have shown promise in other medical applications. In this context, nitractin (Fig. 1B) effectively combats the trachoma virus and displays antibacterial activity8. Idoxuridine (Fig. 1c) was also initially designed for cancer but transformed into a topical antiviral for herpes simplex keratitis. In addition, the compound (R)-SQ 32,926 (Fig. 1D), structurally similar to widely used calcium channel blockers, exhibits intriguing hypertensive effects9. On the other hand, emivirine (Fig. 1E) was developed as an HIV treatment, functioning as a non-nucleoside reverse transcriptase inhibitor10,11. Also, the discovery of the anticancer properties of 5-fluorouracil (Fig. 1F) led to the incorporation of fluorinated groups in medicinal chemistry. This compound disrupts DNA synthesis by irreversibly binding to the thymidylate synthase enzyme due to its structural similarity to uracil. Finally, monastrol (Fig. 1G) and its derivatives including enastron (Fig. 1H) and piperastrol (Fig. 1I) are notable DHPMs/DHPMTs compounds12. They exhibit promise for cancer chemotherapy by inhibiting kinesin-5, a key protein involved in mitosis regulation. Overall, DHPMs/DHPMTs compounds have demonstrated their versatility and therapeutic potential in various medical applications, from BPH treatment to antivirals, hypertension management, and cancer chemotherapy. Therefore, their unique chemical structure and pharmacological properties continue to be studied and utilized in the development of new and effective medications.

Typical examples of biologically active 3,4-dihydropyrimidine-2(1H)-one/thione (DHPM/DHPMT) derivatives.

The inherent biological potential of DHPM/DHPMT derivatives has led to the development of numerous synthetic methods for their preparation. Among the diverse strategies employed, the most notably efficient, straightforward and adaptable method for preparing of diverse DHPM/DHPMT derivatives is the one-pot three-component Biginelli condensation involving aldehydes, 1,3-dicarbonyl compounds, and urea/thiourea. In the meantime, the pivotal role of various catalysts especially heterogeneous catalysts with nano dimensions in facilitating the synthesis of nitrogen containing heterocyclic compounds through the Biginelli reaction is unequivocal13,14,15,16,17. These catalysts play a crucial role in enhancing the efficiency and selectivity of the synthesis process, underscoring their undeniable importance in the field18. Thus far, a diverse array of homogeneous or heterogeneous catalysts, including 1-dodecyl-3-(3-sulfopropyl)-imidazolium hydrogen sulfate [C3SO3HDoim]HSO420, l-proline nitrate21, 1-sulfopyridinium chloride [pyridine-SO3H]Cl22, zirconium (IV)-salophen perfluorooctanesulfonate23, triethylammonium acetate ionic liquid [Et3NH][CH3COO]24, MNPs-IL-HSO425, [bmim(SO3H) (OTf)]26, (BMI)BF4, (BMI)PF6 and (BMI)NTf227, coconut husk ash twisted graphene28, 1-butyl-3-carboxymethyl-benzotriazolium trifluoroacetate [C2O2BBTA][TFA]29, (3-(2-carboxy benzoyl)-1-methyl-1H-imidazol-3-ium chloride [Cbmim]Cl30, COF-IM-SO3H31, Fe3O4@Nb2O532, 1-butyl-1,3-thiazolidine-2-thione p-toluene sulfate [Btto][p-TS]33, p-sulfonic acid calix[4]arene (CX4)34, preyssler heteropoly acid H14NaP5W29MoO110 over SiO2 (PASi)35, boric acid [B(OH)3] supported on Fe3O4@MCM-4136, Fe3O4@SiO2@GP/Picolylamine-Cu(II)37, Bi(NO3)3, ZnO@SBA-1538, ZnO@SBA-15 (Si/Al = 7)39, isocyanurate-based periodic mesoporous organosilica40, iron oxide41, l-asparagine–EDTA–amide silica-coated MNPs42, silicasulfuric acid6, sulfamic acid pyromellitic diamide-functionalized MCM-4143, NFS-PRS9, zwitterionic MSI and TRIP44, [P4-VP]-Fe3O4-HSO4 ionic liquid45, nano-y-Fe2O3-SO3H46, MgFe2O4/cellulose/SO3H11, Magnetic Boron Nitride47, Zn coordination polymer48, perovskite photocatalyst under visible-light49, photoexcited Na2 Eosin Y50, 1,3,5-tris(2-hydroxyethyl)isocyanurate functionalized graphene oxide51, have been employed in the synthesis of DHPM/DHPMT derivatives.

The synthesis of DHPM/DHPMT derivatives faces challenges such as the use of toxic solvents, expensive catalysts, and tedious work-up processes. The unique characteristics of DHPM/DHPMT derivatives and the ongoing challenges in their synthesis have encouraged us for an innovative and efficient approach. In continuation of our interest in the synthesis of organic heterocycles according to the principles of green chemistry in the presence of MNPs40,42, 43, 51,52,53,54,55,56,57,58,59,60,61,62,63,64, we have investigated a novel method that demonstrates the catalytic capabilities of magnetic bismuth ferrite nanoparticles (BFO MNPs) to address present challenges and improves the entire synthetic process (Fig. 2).

One-pot three-component synthesis of highly substituted 3,4-dihydropyrimidine-2(1H)-one/thione derivatives catalyzed by the magnetic BiFeO3 nanoparticles (BFO MNPs) under green conditions.

All used chemicals and reagents including ethyl acetoacetate, urea or thiourea, and aldehydes were purchased from Merck or Sigma Aldrich. Additionally, pure distilled H2O and EtOH 96% were used as solvents. A UV lamp emitting light at a wavelength of 254 nm was utilized in conducting the thin-layer chromatography (TLC) experiments. The identification of the BFO MNPs as well as products was achieved on a Shimadzu FTIR 8400S spectrometer by using KBr disks. Furthermore, 1H NMR spectra were recorded using a Bruker Avance 500 in DMSO-d6 solvent at ambient temperature. The melting points were measured using a 9100 Electrothermal apparatus and are uncorrected. The reported yields are calculated based on the isolated products obtained after the purification process.

Preparation of the BFO MNPs was carried out through the solid-state thermal decomposition method65,66. Initially, a 100 ml round-bottom flask was charged with glycine (8.0 mmol), Fe(NO3)3 (4.0 mmol), Bi(NO3)3 (4.0 mmol), and deionized water (40.0 ml) and the obtained mixture was heated at 120 °C for one h. Subsequently, HNO3 (63%, d = 1.4 g ml−1, 2.80 ml) was added dropwise to the reaction mixture. The reaction mixture was subjected to heating at 120 °C, resulting in the formation of a brown solid. Finally, the brown solid was put in a furnace for one h at 350 °C and further one h at 550 °C to prepare bismuth ferrite nanoparticles (BFO MNPs).

In a 5 ml flask, aldehyde (1a–s, 1.0 mmol), ethyl acetoacetate (2, 1.0 mmol), urea/thiourea (3a–b, 1.10 mmol) and BFO MNPs (312.82 g mol−1, 4.0 mg, 1.28 mol%) were added to a mixture of H2O:EtOH (3.0 ml, v:v, 3:1). The reaction mixture was heated under reflux conditions for the appropriate time as indicated in Table 2. The reaction progress was monitored using thin-layer chromatography (TLC). After completion of the reaction, EtOAc (2 × 2 ml) was added and stirred for 10 min. The BFO MNPs were separated from the obtained mixture by applying an external magnet and collected for next runs by keeping them in an oven at 70 °C for 2 h. The filtrate was separated by using a separatory funnel. The EtOAc phase was kept in a 10 ml beaker at ambient temperature to afford recrystallized DHPMs/DHPMTs products with high purities.

Ethyl 6-methyl-4-(3-nitrophenyl)-3,4-dihydropyrimidine-2(1H)-one-5-carboxylate; White solid; M.P: 220–221 °C; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 1.10 (t, J = 7.3 Hz, 3H, CH3), 2.28 (s, 3H, CH3), 4.00 (q, J = 7.3 Hz, 2H, CH2), 5.31 (d, J = 3.0 Hz, 1H, CH), 7.66 (t, J = 8.0 Hz, 1H, Ar–H), 7.70 (d, J = 7.5 Hz, 1H, Ar–H), 7.90 (brs, 1H, NH), 8.09 (s, 1H, Ar–H), 8.14 (d, J = 8.0 Hz, 1H, Ar–H), 9.37 (s, 1H, NH).

Ethyl 4-(3,4-dichlorophenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-one-5-carboxylate; White solid; M.P: 228–230 °C; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 1.01 (t, J = 7.0 Hz, 3H, CH3), 2.30 (s, 3H, CH3), 3.90 (q, J = 7.0 Hz, 2H, CH2), 5.60 (s, 1H, CH), 7.32 (d, J = 8.3 Hz, 2H, Ar–H), 7.42 (d, J = 8.3 Hz, 2H, Ar–H), 7.57 (s, 1H, Ar–H), 7.57 (s, 1H, NH), 9.34 (s, 1H, NH).

Ethyl 4-(3,4-dimethoxyphenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-one-5-carboxylate; White solid; M.P: 173–175 °C; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 1.12 (t, J = 6.8 Hz, 3H, CH3), 2.25 (s, 3H, CH3), 3.77 (s, 6H, 2 OCH3), 4.00 (q, J = 6.8 Hz, 2H, CH2), 5.11 (s, 1H, CH), 6.73 (d, J = 8.0 Hz, 1H, Ar–H), 6.85 (s, 1H, Ar–H), 6.90 (d, J = 8.0 Hz, 1H, Ar–H), 7.67 (s, 1H, NH), 9.15 (s, 1H, NH).

Ethyl 6-methyl-4-(thiophen-2-yl)-3,4-dihydropyrimidine-2(1H)-one-5-carboxylate; White solid; M.P: 214–216 °C; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 1.17 (t, J = 7.0 Hz, 3H, CH3), 2.23 (s, 3H, CH3), 4.07 (q, J = 7.0 Hz, 2H, CH2), 5.42 (d, J = 3.0 Hz, 1H, CH), 6.89 (m, 1H, Het Ar–H), 6.94 (t, J = 4.0 Hz, 1H, Het Ar–H), 7.33 (d, J = 5.0 Hz, 1H, Ar–H), 7.90 (s, 1H, NH), 9.31 (s, 1H, NH).

Ethyl 6-methyl-4-phenyl-3,4-dihydropyrimidine-2(1H)-2-thione-5-carboxylate; White solid; M.P: 211–213 °C; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 1.10 (t, J = 7.0 Hz, 3H, CH3), 2.30 (s, 3H, CH3), 4.00 (q, J = 7.0 Hz, 2H, CH2), 5.19 (s, H, CH), 7.23 (d, J = 7.0 Hz, 2H, Ar–H), 7.28 (t, J = 7.5 Hz, 1H, Ar–H), 7.35 (t, J = 8.0 Hz, 2H, Ar–H), 9.65 (s, 1H, NH), 10.33 (s, 1H, NH).

Characterization of nanoparticles typically involves various techniques to understand their size, shape, composition, surface properties, and other relevant characteristics. To confirm the structure and surface characteristics of the prepared magnetic BFO MNPs nanoparticles, several analyses were employed. These analyses include Fourier transform infrared spectroscopy (FTIR) for identifying functional groups through vibrational modes, field-emission scanning electron microscopy (FESEM) for detailed imaging to reveal information about size and morphology, energy-dispersive X-ray spectroscopy (EDS) for determining the elemental composition of the nanoparticles, X-ray powder diffraction (XRD) for determining the crystallinity degree of structure and providing insights into composition and arrangement, Brunauer–Emmett–Teller (BET) for assessing specific surface area and porosity, and vibrating sample magnetometry (VSM) technique for measuring magnetic properties including magnetic moment, magnetic susceptibility, and coercivity.

The FTIR spectrum of BFO MNPs nanoparticles prepared utilizing glycine, as a chelating agent, demonstrates apparent characteristics spanning the spectral range of 400–4000 cm⁻1 (Fig. 3). The obvious broad peak positioned at 3300–3500 cm⁻1 indicates the stretching vibrations of the hydroxyl (OH) groups located on the surface of the obtained nanomaterial. Additionally, the presence of peaks at 550 and 450 cm⁻1 is ascribed to the stretching vibrations associated with the iron-oxygen (Fe‒O) and bismuth-oxygen (Bi‒O) bonds stretching vibrations, respectively. These findings in the FTIR spectrum provide valuable insights into the structural and chemical composition of the prepared BiFeO₃ nanoparticles67.

FTIR spectrum of the BFO MNPs.

FESEM images of BiFeO₃ nanoparticles (at the scales of 50, 5 and 3 μm) indicate a spongy network with attached frog-like units, which having high porosity and microporous dimensions. These pores originate from the swift release of gases generated during nitrate combustion. Furthermore, upon analyzing of the images at the scales less than 3 μm, including 1 μm as well as 700 and 500 nm, it becomes apparent that the morphology of BFO MNPs consists of nanolayers arranged in close nearby, with micro-sized cavities formed between the layers (Fig. 4).

FESEM images of BiFeO3 nanoparticles at (A) 50 μm, (B) 5 nm, (C) 3 μm and (D) 1 μm, (E) 700 nm, and (F) 500 nm scales.

As shown in the Fig. 5, the elemental mapping analysis of the BFO MNPs catalyst clearly confirms the existence of Fe, O, and Bi elements in the composition of the nanomaterial. In addition, the mapping elemental analysis demonstrates a uniform distribution of desired elements. Furthermore, the identification of Bi, Fe, and O elements in the EDS analysis serves as additional evidence supporting the successful preparation of BFO MNPs (Fig. 6).

EDS elemental mapping analysis of the BFO MNPs.

Elemental analysis by energy-dispersive X-ray spectroscopy (EDS) of the BFO MNPs.

The X-ray diffraction (XRD) analysis of the bismuth ferrite nanostructure is illustrated in Fig. 7. The XRD pattern of the BFO MNPs exhibits characteristic peaks at 2θ of 22.2, 27.8, 31.8, 39.2, 51.1, 56.1, and 86.7°, offering detailed information about the crystalline structure of BFO MNPs. By comparing the findings of the XRD analysis with recent reports, it becomes evident that the crystal structure of BFO MNPs has been successfully established (JCPDS card number 01-073-0548). Also, employing Scherer's equation for particle size calculation at 2θ = 22.2 and a full width at half maximum (FWHM) of 0.448 shows a determined particle size of 18.9 nm68.

XRD pattern of the BFO MNPs.

The magnetization curve for the magnetic BFO MNPs is presented in Fig. 8, offering a comprehensive visualization of the magnetic properties of the prepared nanoparticles. A noteworthy ferromagnetic response is detected in the BFO MNPs, exhibiting a saturation magnetization of 4.60 emu.g−1. This observed behavior aligns cohesively with the findings reported in earlier studies on BiFeO3 nanoparticles, particularly when the average diameter size is maintained below 62.0 nm. This consistency in the magnetic properties underscores the reliability and reproducibility of the observed ferromagnetic characteristics, contributing to the growing body of knowledge surrounding magnetic nanoparticles, specifically those composed of bismuth ferrite69,70.

Hysteresis diagram of the magnetic bismuth ferrite nanoparticles (BFO MNPs).

The nitrogen adsorption–desorption isotherm of the BFO MNPs was studied to determine their surface area (Fig. S14). The specific BET surface area for the prepared BFO MNPs sample was found to be 24.81 m2.g−1. The proper surface to volume ration of the BFO MNPs, contributing to a substantial surface area, serves as a significant indicator of the appropriate characteristics of this particular surface. Furthermore, Barrett-Joyner-Halenda (BJH) pore size was mainly found to be at the range of 8.0 and 12.0 nm (Fig. S15).

To study the synthesis of DHPM/DHPMT derivatives in the presence of BFO MNPs, a model reaction comprising of benzaldehyde (1a), ethyl acetoacetate (2), and urea (3a) was chosen. Various influencing parameters, including catalyst and solvent type, catalyst loading, and temperature were systematically studied. The results of these experiments have been summarized in Table 1. Initially, the progress of the model reaction was examined under conditions without a catalyst, both at room temperature and under reflux conditions, using water as the solvent. The results showed that only trace amounts of the desired product, ethyl 6-methyl-4-(phenyl)-3,4-dihydropyrimidine-2(1H)-one-5-carboxylate (4a), were obtained even after 6 h (Table 1, entries 1,2). In the next experiments, the catalytic performance of different nanoparticles, including Fe3O4, MnFe2O4, CuFe2O4, ZnFe2O4, NiFe2O4, and BiFeO3 (BFO MNPs), was investigated in the model reaction at room temperature (Table 1, entries 3–8). The obtained findings indicated the superior performance of the BFO MNPs compared to other magnetic nanoparticles in the model reaction (Table 1, entry 8). After selecting of the BFO MNPs as the optimal catalyst, the efficiency of various solvents such as MeOH, EtOH, EtOAc and CH3CN as well as mixtures of H2O:MeOH (3:1) and H2O: EtOH (3:1) on the yield of the model reaction was evaluated (Table 1, entries 9–14). The obtained results revealed that the mixture of H2O: EtOH (3:1), as a solvent, exhibited the most significant impact, leading to a product yield of 67% (Table 1, entry 14). This observation can be explained by a combination of factors: the improved dispersibility of the BFO MNPs in the H2O: EtOH medium, the solubility of the substrates in this solvent, and the fact that the resulting DHPMs with higher molecular weights do not dissolve in this mixture. Increasing the catalyst loading to improve the model reaction, particularly in terms of yield and reaction time, was investigated in the next step. It was found that increasing the catalyst loading from 2.0 to 4.0 mg enhances the model reaction yield from 67 to 84%, accompanied by a notable reduction in reaction time from 45 to 20 min (Table 1, entry 15). Finally, the model reaction was examined under the reflux conditions. By increasing the reaction temperature from 25 °C to reflux conditions, higher yield of the desired product (93%) was obtained (Table 1, entry 16). Therefore, the optimized conditions were considered to be 4.0 mg loading of BFO MNPs in a mixture of H2O: EtOH (3.0 ml, 3:1) under reflux conditions.

To demonstrate the efficiency and general scope of the optimized conditions, the conditions was applied to the synthesis of various derivatives of DHPMs/DHPMTs 4a–y. This was achieved through a one-pot three-component reaction involving different aryl/heteroaryl aldehydes 1a–s, ethyl acetoacetate (2), and urea/ thiourea (3a–b) components. The obtained results have been summarized in Table 2. Interestingly, all studied aldehydes 1, even sensitive aldehydes to polymerization under acidic conditions such as thiophen-2-carbaldehyde (1q) and furfural (1r), survived very well under the optimized conditions to afford corresponding DHPMs/DHPMTs 4a–y in high to excellent yields.

According to the data presented in Table 2, aromatic aldehydes with electron-withdrawing groups (‒NO2, ‒Cl, ‒Br and ‒CHO) show faster formation of the desired products 4b–i and 4s–u compared to the benzaldehyde as well as aromatic aldehydes containing electron-donating groups (–OMe, –OH, –Me) to afford 4a, 4n–p and 4v–w, respectively. This can be attributed to the higher carbonyl activity of aldehydes with electron-withdrawing groups, which facilitate the reaction and leads to accelerated product formation. In this context, electron-rich heterocyclic aromatic aldehydes including thiophen-2-carbaldehyde (1q) and furfural (1r) exhibit prolonged reaction times compared to benzaldehyde (1a). The observed behavior can be assigned to their higher electron density and lower carbonyl activity in these compounds compared to aromatic carbocyclic aldehydes. Indeed, the increased electron density in these five-membered heterocyclic aldehydes hinders the attack of both enol form of ethyl acetoacetate (2) and urea/ thiourea (3a-b), as electrophile, on their carbonyl groups. Consequently, slower product formation and lower yields would be observed. These trends in reaction rates and the obtained yields is in consistence with the observed reaction mechanism, which suggests that the attack of an electrophile on the carbonyl group is the rate determining step.

The proposed mechanism for the one-pot multi-component synthesis of DHPM/DHPMT derivatives in the presence of BiFeO3 magnetic nanoparticles has been depicted in Fig. 9. In the first step of the mechanism, the carbonyl group of the aromatic aldehyde 1 is activated by BiFeO3 nanoparticles. The bismuth as well as Fe cations on the surface of the nanoparticles act as active Lewis acid centers and coordinate with the carbonyl group of aldehydes 1, enhancing their reactivity. Then, the nitrogen from urea or thiourea (3a–b) attacks, as a nucleophile, onto the activated carbonyl group by the BFO MNPs leading to the formation of hemiaminal intermediate (Int. 1). Then, this intermediate produces the imine intermediate (Int. 2) by omitting a water molecule. The next step involves the nucleophilic addition of the enol form of ethyl acetoacetate (2’), with proper concentration produced by the BFO MNPs, to the imine intermediate. This Michael addition leads to the formation of intermediate (Int. 3). Finally, the desired DHPMs/DHPMTs products 4a–y are formed through intramolecular condensation catalyzed by the BFO MNPs. This condensation involves the reaction between the remaining amine group of urea or thiourea and the keto group of ethyl acetoacetate moiety, resulting in the removal of H2O and the formation of the final products 4a–y.

Proposed mechanism for the synthesis of 3,4-dihydropyrimidine-2(1H)-one/thione derivatives in the presence of magnetic BFO MNPs nanocatalyst.

The recyclability and reusability of catalysts are important aspects in the field of green chemistry. Heterogeneous catalysts, despite their lower efficiency compared to homogeneous catalysts, are preferred due to their ability to be easily separated and reused. To verify the heterogeneity of the BFO MNPs nanocatalyst in this study, hot filtration test was conducted. After 5 min from the start of the reaction, the magnetic catalyst was separated from the reaction mixture by using an external magnet. The reaction mixture was then stirred for an additional 30 min at room temperature without the catalyst. The results showed that only 51% of the desired product was obtained after this duration, suggesting that the Bi and Fe ions present in the structure of BFO MNPs nanoparticles were absent in the reaction medium and confirms its heterogeneity. This finding is significant as it demonstrates the potential for the BFO MNPs nanocatalyst to be separated and reused, enhancing its practical applications and aligning with the principles of green chemistry.

The recyclability of the BFO MNPs was assessed to determine their potential for multiple uses. The BFO MNPs were isolated from the reaction mixture using an external magnet and then washed with EtOAc and EtOH to remove any impurities. After drying at 70 °C for 2 h, the BFO MNPs were used again in the same model reaction. As depicted in Fig. 10, repeated runs of the model reaction by using the recycled BFO MNPs catalyst showed high conversion rates, indicating their appropriate catalytic activity. After five replications of the model reaction using the recycled BFO MNPs catalyst, an average yield of 86% was obtained. These results highlight the stability and recyclability of the BFO MNPs, as a proper heterogeneous nanocatalyst, for the Biginelli three-component reaction. The fact that the recycled catalyst consistently maintained high conversion rates suggests that it can be reused multiple times without significant loss of its activity. Also, XRD analysis of the recycled catalyst, after its washing and drying, was performed. The result has been shown in Fig. S18. Interestingly, the result demonstrated that the catalyst structure remained almost intact through multiple reuse cycles. Overall, these findings demonstrate the promising potential of BFO MNPs nanoparticles as a stable and efficient heterogeneous nanocatalyst under optimal reaction conditions.

The results of recyclability and reusability of the BFO MNPs nanoparticles in the model reaction.

Ultimately, the effectiveness of the BFO MNPs catalyst was assessed in comparison to previously reported protocols. As outlined in Table 3, the BFO MNPs nanocatalyst developed in this study exhibits notable efficiency in the rapid synthesis of DHPMs/DHPMTs. Additionally, an individual characteristic of this catalyst is its capability to facilitate the formation of DHPMs/DHPMTs products under environmentally friendly conditions and green chemistry principles.

In brief, the efficacy of magnetic bismuth ferrite magnetic nanoparticles (BFO MNPs), as a heterogeneous Lewis acidic catalyst, for the synthesis of diverse derivatives of pharmacologically-active 3,4-dihydropyrimidin-2 (1H)-ones/thiones (DHPMs/DHPMTs) was explored. The catalytic performance of the BFO MNPs demonstrated notable dependence to the solvent and temperature. The corresponding DHPMs/DHPMTs were obtained in a mixture of H2O:EtOH, as a green solvent, through the one-pot Biginelli three-component reaction strategy. The presented method offers several noteworthy advantages including high to excellent yields of the desired products, low catalyst loading and short reaction times. Moreover, this approach eliminates the need for toxic organic solvents and ensures a simplified purification of the desired products, facilitates a straightforward workup process, and allows for the recyclability and reusability of the BFO MNPs catalyst for at least five runs without significant loss of its catalytic activity. This environmentally-benign methodology demonstrates the potential of the catalyst for more sustainable and efficient practices in green chemistry.

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

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The authors would like to express their gratitude to the Research Council of Iran University of Science and Technology, Tehran (IUST) for their financial support (grant no 160/23372). We would also like to acknowledge the support of the Iran Nanotechnology Initiative Council (INIC) and Iran National Science Foundation (INSF).

Pharmaceutical and Heterocyclic Compounds Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran

Safa Hanifi & Mohammad G. Dekamin

Department of Chemistry, Behbahan Khatam Alanbia University of Technology, Behbahan, 63616-63973, Iran

Mohammad Eslami

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Safa Hanifi: Investigation, Formal analysis, Writing-original draft; Mohammad G. Dekamin: Conceptualization, Formal analysis, Financial, Editing-Final draft; Mohammad Eslami: Conceptualization, Formal analysis, Investigation, Writing-original draft.

Correspondence to Mohammad G. Dekamin.

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Hanifi, S., Dekamin, M.G. & Eslami, M. Magnetic BiFeO3 nanoparticles: a robust and efficient nanocatalyst for the green one-pot three-component synthesis of highly substituted 3,4-dihydropyrimidine-2(1H)-one/thione derivatives. Sci Rep 14, 22201 (2024). https://doi.org/10.1038/s41598-024-72407-x

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Received: 06 March 2024

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Published: 27 September 2024

DOI: https://doi.org/10.1038/s41598-024-72407-x

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