Fe3O4@SiO2-LY-C-D-Pd as a new, effective, and magnetically recoverable catalyst for the synthesis of 1H-tetrazoles and asymmetric biphenyls

Materials and characterization

The materials and solvents used in this study were obtained from Sigma-Aldrich, Fluka, or Merck and utilized directly without further purification.

Preparation of Fe₃O₄@SiO₂-LY-C-D-Pd

The synthesis process began with the preparation of Fe₃O₄@SiO₂ using the co-precipitation method^36,37. To introduce l-lysine functional groups onto the Fe₃O₄@SiO₂ surface, 1 g of the synthesized Fe₃O₄@SiO₂ was suspended in 30 mL of ethanol solution. Gradually, 1.5 mmol or 0.219 g of l-lysine was added to this solution while ensuring continuous mixing. The resulting mixture underwent stirring under reflux conditions over a duration of 24 h to achieve functionalization. Following this, the solid material was carefully separated through filtration, washed multiple times with ethanol to remove impurities, and subsequently air-dried at ambient temperature. To synthesize Fe₃O₄@SiO₂-LY-C, 1 g of the l-lysine-functionalized Fe₃O₄@SiO₂ (denoted as Fe₃O₄@SiO₂-LY) was dispersed uniformly in 40 mL of tetrahydrofuran (THF) via sonication for 30 min to ensure homogeneity. Afterward, 2.5 mmol or 0.461 g of cyanuric chloride was added to the reaction vessel, and the reaction mixture was stirred at room temperature for 24 h to facilitate covalent attachment. Upon completion of the reaction, the resulting Fe₃O₄@SiO₂-LY-C product was isolated using magnetic separation. The solid material was then thoroughly washed three times with fresh THF to remove any unreacted reagents and by-products. Following this purification step, the material was dried in an oven set at 40 °C for 5 h. To further modify this intermediate product, the dried Fe₃O₄@SiO₂-LY-C sample was treated with a mixture of 40 mL of acetonitrile and 1 mL of diisopropylethylamine. Subsequently, 7 mmol (equivalent to 1.2 g) of dipyridylamine was introduced into the reaction mixture. This suspension was initially stirred at room temperature for 2 h to ensure proper interaction between the reactants and then subjected to reflux conditions for an extended period of 20 h to allow the reaction to proceed to completion. Afterward, the solid products were separated using an external magnet, followed by thorough washing with deionized water and acetone to remove residual reactants. Finally, the solid product was oven-dried at a controlled temperature of 50 °C for 12 h. To synthesize the final Fe₃O₄@SiO₂-LY-C-D-Pd nanocatalyst, a mixture containing 1 g of the Fe₃O₄@SiO₂-LY-C-D precursor, 2.5 mmol of palladium acetate (Pd(OAc)₂), and 40 mL of ethanol was prepared and added to a reaction vessel. This mixture was stirred under reflux conditions for 24 h to facilitate palladium loading onto the nanostructure. Subsequently, 1.6 mmol of sodium borohydride (NaBH₄) was gradually introduced into the flask to promote the reduction of palladium ions to metallic palladium particles. This reduction process was carried out with agitation over a period of 6 h. Once complete, the resulting nanocatalyst was separated using magnetic extraction and subjected to multiple rinse cycles with ethanol and water to ensure thorough purification. Finally, the nanocatalyst was dried under vacuum conditions at 50 °C, producing the final product ready for catalytic applications (Fig. 1).

Synthetic route for Fe₃O₄@SiO₂-LY-C-D-Pd.

General procedure for the Suzuki reactions

In a 25 mL round bottom flask, aryl halide (1.0 mmol), phenylboronic acid (1.0 mmol or 0.129 g), K₂CO₃ (1.5 mmol or 0.207 g), and Fe₃O₄@SiO₂-LY-C-D-Pd (30 mg) were added to DMSO (4 mL) and stirred at 120 °C for 30 min. After the reaction was finished (monitored via thin-layer chromatography), 10 mL of EtOAc was added to the reaction mixture, and the nanocatalyst was separated using a magnet. The organic phase yielded biphenyl compounds through solvent evaporation (Fig. 2).

Fe₃O₄@SiO₂-LY-C-D-Pd‐catalysed Suzuki reaction.

General procedure for synthesis of 1H‐tetrazoles

A reaction involved combining 1.3 mmol or 0.084 g of sodium azide, 1 mmol of nitrile, and 0.03 g of Fe₃O₄@SiO₂-LY-C-D-Pd in PEG-400 (2 mL) and stirring the mixture at 120 °C. After completion, determined by TLC monitoring, the mixture was allowed to cool to room temperature. The catalyst was separated using a magnet, and HCl (4 N, 2 mL) was added to the filtered solution. The resulting tetrazole was extracted with ethyl acetate, and the organic phase was washed with distilled water, dried with anhydrous sodium sulfate, and concentrated to yield the crude solid product (Fig. 3).

Synthesis of ¹H-tetrazoles in the presence of Fe₃O₄@SiO₂-LY-C-D-Pd.

Catalyst characterizations

FT-IR analysis (Fig. 4) shows the FT-IR spectra of Fe₃O₄, Fe₃O₄@SiO_2, Fe₃O₄@SiO₂-LY, Fe₃O₄@SiO₂-LY-C, Fe₃O₄@SiO₂-LY-C-D and Fe₃O₄@SiO₂-LY-C-D-Pd MNPs. The two absorption bands at 650 cm⁻¹ are attributed to the stretching vibrations of iron-oxygen bonds. In Fig. 1a, the bending and stretching vibrations of OH molecules present on the nanoparticle surface are observed at 3435 cm⁻¹. Figure 4b illustrates the occurrence of a condensation reaction between the hydroxyl groups of Fe₃O₄ nanoparticles (MNPs) and the alkoxysilane molecules of TEOS, forming the first layer. The peak at 1068 cm⁻¹ confirms the presence of Si–O–Si stretching vibrations, which correspond to the silica shell. In Fig. 4c, for Fe₃O₄@SiO₂-LY, the bands observed at 2889 and 2809 cm⁻¹ correspond to the bending vibration of CH₂, confirming the successful attachment of l-lysine chain molecules. In Fig. 4d, the emergence of new bands at 1458 and 1561 cm⁻¹ (from the Fe₃O₄@SiO₂-LY@C spectrum) signifies the presence of an aromatic triazine ring in the Fe₃O₄@SiO₂-LY-C sample, confirming the stabilization of cyanuric chloride. The incorporation of pyridine groups is validated through bands appearing at 3050 cm⁻¹ (aromatic C-H stretching) and 1653 cm⁻¹ (C-N stretching). These results indicate that Fe₃O₄@SiO₂ has been successfully functionalized with melamine-containing pyridine groups, as shown in Fig. 4e. Additionally, the peak at 1653 cm⁻¹ in Fig. 4e signifies metal–ligand coordination, with its shift to a lower frequency range (1653–1632 cm⁻¹) further confirming the successful binding of palladium ions (Pd) with the organic ligand, as depicted in Fig. 4f^37,38.

Comparative study of FTIR spectra of (a) Fe₃O₄, (b) Fe₃O₄@SiO₂, (c) Fe₃O₄@SiO₂-LY (d) Fe₃O₄@SiO₂-LY@C, (e) Fe₃O₄@SiO₂-LY-C-D (f) Fe₃O₄@SiO₂-LY-C-D-Pd.

Figure 5 illustrates the normal-angle powder X-ray diffraction (XRD) patterns of Fe₃O₄@SiO₂-LY-C-D-Pd. The XRD pattern closely resembles that of Fe₃O₄, confirming the presence of octahedral structures. The successful synthesis of Fe₃O₄ nanoparticles (MNPs) is evident from the peak positions observed at 2θ = 31°, 37°, 44°, 56°, 61°, and 68°, which correspond to the (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1), and (4 4 0) crystal plane reflections, respectively. Moreover, the XRD data confirm a cubic spinel crystalline structure characteristic of Fe₃O₄. These results suggest that the structural integrity of Fe₃O₄ was retained during the preparation of the LY-C-D-Pd-supported catalyst, with its crystalline phase and structural characteristics remaining largely unaltered.

XRD spectrum of Fe₃O₄@SiO₂-LY-C-D-Pd.

The thermal behavior of the Fe₃O₄@SiO₂-LY-C-D-Pd complex nanocomposite was analyzed using TGA, as illustrated in Fig. 6. The analysis revealed two distinct weight loss regions. The first, approximately 5%, occurred below 250 °C and was attributed to the removal of organic solvents trapped within the catalyst structure. The second weight loss, around 26%, was observed between 250 and 600 °C, corresponding to the decomposition of the organic layer and the Pd complex attached to Fe₃O₄ (Fig. 6). These findings confirmed the successful chemisorption of the LY-C-D-Pd complex onto the surface of Fe₃O₄@SiO₂ MNPs.

TGA curve of Fe₃O₄@SiO₂-LY-C-D-Pd.

The elemental composition of Fe₃O₄@SiO₂-LY-C-D-Pd was determined from the EDX spectrum (Fig. 7). Figure 7 confirms the presence of Silicon, Iron, Nitrogen, Oxygen, Carbon, and Palladium in the catalyst and proves the successful synthesis of nanoparticles. The results confirmed the successful immobilization of LY-C-D-Pd on the surface of Fe₃O₄@SiO₂ MNPs.

EDS analysis of Fe₃O₄@SiO₂-LY-C-D-Pd.

The size and morphology of the synthesized Fe₃O₄@SiO₂-LY-C-D-Pd particles were analyzed using scanning electron microscopy (SEM). The SEM image revealed the formation of uniform, single-dispersed nanoparticles. A closer examination of the magnified image indicated slight aggregation and stacking textures, likely caused by magnetic interactions within the catalyst’s particle structure (Fig. 8). The average particle size was measured to range between 38 and 93 nm.

SEM images of Fe₃O₄@SiO₂-LY-C-D-Pd.

Figure 9 presents the XPS spectrum of the synthesized Fe₃O₄@SiO₂-LY-C-D-Pd catalyst, showcasing peaks corresponding to oxygen, carbon, silicon, nitrogen, palladium, and iron (Fig. 9a). The oxidation state of palladium was examined through XPS analysis, as shown in Fig. 9b. To determine this oxidation state, X-ray photoelectron spectroscopy (XPS) studies were conducted, revealing two distinct binding energy peaks at 333.4 eV and 342.6 eV. These peaks are attributed to Pd 3d_3/2 and Pd 3d_5/2, respectively. Based on this analysis, the XPS data confirms the structure of the synthesized Fe₃O₄@SiO₂-LY-C-D-Pd catalyst.

XPS spectrum of Fe₃O₄@SiO₂-LY-C-D-Pd catalyst.

The pore size and surface area distribution of Fe₃O₄@SiO₂-LY-C-D-Pd were carefully examined using the N₂ adsorption–desorption isotherms technique, as illustrated in Fig. 10. This method revealed that the surface area of Fe₃O₄@SiO₂-LY-C-D-Pd is 6.15 m²/g. Furthermore, the Barrett–Joyner–Halenda (BJH) method provided details about the pore size distribution and volume, showing dimensions of 40.56 nm for pore size and a pore volume of 0.06 cm³/g.

N₂-adsorption isotherms of Fe₃O₄@SiO₂-LY-C-D-Pd.

In addition, an ICP-OES analysis was conducted to determine the quantity of Pd in Fe₃O₄@SiO₂-LY-C-D-Pd. According to the analysis, the Pd content in the catalyst was measured at 1.5 × 10^–4 mol g⁻¹. Furthermore, the extent of Pd leaching following the catalyst’s recycling was examined through ICP analysis. The findings reveal that the levels of Pd in the reused catalysts are 1.4 × 10^–4 mol g⁻¹, indicating minimal Pd leaching from the Fe₃O₄@SiO₂-LY-C-D-Pd framework.

The magnetic properties of uncoated magnetic spinel ferrite (Fe₃O₄) and Fe₃O₄@SiO₂-LY-C-D-Pd MNPs were examined through VSM analysis within the external magnetic field range of − 10,000 to + 10,000 Oe at room temperature (see Fig. 11). As shown in Fig. 11, the decrease in saturation magnetization from approximately 40 emu/g to about 29 emu/g can be attributed to the presence of the new coated layer, serving as evidence of the successful synthesis of the catalyst. Though the Ms level of the Fe₃O₄@SiO₂-LY-C-D-Pd is lower than that of the Fe₃O₄ NPs its magnetic sensitivity is sufficient for its magnetic removal from different reaction mediums.

VSM curves of (a) Fe₃O₄ (b) Fe₃O₄@SiO₂-LY-C-D-Pd.

Catalytic studies

The Fe₃O₄@SiO₂-LY-C-D-Pd catalyst was studied for its efficiency in synthesizing biaryls through the Suzuki cross-coupling reaction. Iodobenzene and PhB(OH)₂ were selected as the model reactants for this investigation. Reaction conditions were optimized by varying the amount of catalyst, solvent, temperature, and other parameters. According to Table 1, no reaction occurred in the absence of the catalyst, even after an extended period (entry 1). Using 8 mg of the catalyst resulted in a low product yield (entry 2). However, when 30 mg of the catalyst was employed with suitable proportions of aryl halide and PhB(OH)₂, optimal performance was achieved. Increasing the temperature to 120 °C resulted in a high product yield within just 30 min. Further optimization involved testing different bases, such as K₂CO₃, KOH, and NaOH. Among them, K₂CO₃ proved most effective, providing a 98% yield of the desired biphenyl product within 30 min (entry 5). The solvent selection was also explored using options like DMSO, EtOH, DMF, PEG-400, CH₃CN, water, and a solvent-free system (entries 7–13). The use of DMSO stood out, delivering a 98% yield of biphenyl after 30 min.

After achieving the best conditions for coupling iodobenzene with phenylboronic acid, the catalytic activity of Fe₃O₄@SiO₂-LY-C-D-Pd was expanded to include the coupling of other aryl halides with phenylboronic acid. Furthermore, a variety of aryl bromides, iodides, and chlorides were examined in the coupling reaction with phenylboronic acid using Fe₃O₄@SiO₂-LY-C-D-Pd (Table 2). In this case, the Suzuki–Miyaura reaction successfully yielded the desired biphenyl derivatives from both electron-deficient and electron-rich aryl halides under mild conditions.

Predicting the precise course of a chemical reaction in its entirety can be challenging. However, here we propose a mechanism for the synthesis involved in the Suzuki reaction. In this coupling mechanism, aryl halide undergoes an oxidative addition with Pd(0). Subsequently, the base potassium carbonate activates phenylboronic acid, leading to the formation of a phenyl boronate ester. Next, medium (2) forms through a displacement reaction, where the metal in medium (1) is substituted by the activated borane group. The final step involves an elimination-reduction process, yielding the desired product while regenerating the catalyst for reuse (Fig. 12).

Possible mechanism for Suzuki reaction.

We next focused on the cycloaddition reaction of aryl benzonitriles with sodium azide. To identify the optimal conditions, a representative reaction between benzonitrile and NaN₃ was selected in a 1:1.3 molar ratio, with varying parameters such as solvent, temperature, and catalyst loading using a Pd-anchored catalyst. The findings are summarized in Table 3. The study evaluated key factors, including temperature, different solvents (such as PEG-400, n-Hexane, H₂O, EtOH, CH₃CN, and a solvent-free method), the amount of catalyst, and the quantity of NaN₃ in the reaction model. From the results detailed in Table 3, it was concluded that the optimal conditions for synthesizing 1H-tetrazole derivatives involve using 0.03 g of Fe₃O₄@SiO₂-LY-C-D-Pd in PEG-400 at 120 °C with 1.3 mmol of NaN₃.

After fine-tuning the reaction conditions, the catalytic scope of Fe₃O₄@SiO₂-LY-C-D-Pd was broadened to encompass both aromatic and aliphatic nitrile derivatives. The study particularly concentrated on aromatic nitriles with either electron-withdrawing or electron-donating groups on the aromatic ring to produce corresponding tetrazole derivatives. As shown in Table 4, all products were synthesized within acceptable durations and attained outstanding yields, showcasing the catalyst’s exceptional efficiency. Moreover, para-, meta-, and ortho-substituted benzonitriles were effectively examined. The investigation also extended to aliphatic nitriles, resulting in tetrazole derivatives with excellent yields. An interesting property observed was homoselectivity, where only one similar functional group participates in the reaction. For instance, the catalyst was used to study malononitrile, which contains two identical cyano groups, for tetrazole production. Impressively, Fe₃O₄@SiO₂-LY-C-D-Pd demonstrated high selectivity by reacting with only one cyano group in malononitrile with sodium azide while leaving the other unchanged.

Previous research has outlined an efficient cyclic mechanism for synthesizing 5-substituted 1H-tetrazoles using the Fe₃O₄@SiO₂-LY-C-D-Pd catalyst, as depicted in Fig. 13. In this process, the cyanide functional group is initially activated by palladium metal, enabling its reaction with sodium azide to yield intermediate I. Subsequently, the removal of the catalyst facilitates the formation of intermediate II. In the final step, intermediate II is transformed into the desired tetrazole product through the addition of HCl. Concurrently, the catalyst is regenerated, making it ready to initiate a new reaction cycle.

Proposed Mechanism for tetrazole in the presence of Fe₃O₄@SiO₂-LY-C-D-Pd.