Synthesis of ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocomposite as a superior and reusable heterogeneous catalyst for the preparation of pyrimidine derivatives and investigation of their antimicrobial activities

Abstract

In this report, we synthesized some pyrimidine derivatives by multi-component reaction of urea, benzaldehydes, and 1,3-indandione in the presence of ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocomposite under reflux conditions. Initially, graphene oxide was prepared from graphite, and then it was sulfonated using ClOSO₃H. Next, GO-OSO₃H nanosheets were used to support ZIF-8/ZnFe₂O₄ nanostructure. The construction of the synthesized structure was established using different spectral techniques such as X-ray crystallography (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX/Mapping), Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA), vibrating sample magnetometer (VSM), and Brunauer-Emmett-Teller (BET). The present method provides various benefits including the efficiency of outcomes, easy separation of the catalyst, and excellent yield of the products within short reaction times. Moreover, the antibacterial activities of pyrimidine derivatives were investigated via the agar-well diffusion method on gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria and the obtained results illustrated reasonable effects.

1. Introduction

Heterocyclic compounds are widely distributed in nature and have biological and industrial importance. Today, many drugs contain heterocycles that are not extracted from natural sources, but synthesized in the laboratory [1]. Heterocyclic compounds are of interest to researchers due to their valuable biological actions, as well as antiviral [2], antibacterial [3], anti-inflammatory [4], antitumor [5], and antihypertensive [6]. Meanwhile, clinical properties such as antimicrobial [7], antihistamine, and antiasthmatic [8] have been described for the pyrimidine derivatives.

Metal-organic frameworks (MOFs) have captivated the consciousness of many investigators which are rapidly developing and are characterized by high porosity and abundant properties. MOFs are generally composed of metal clusters with open crystal lattices which are permanently assembled through strong cross-links [9].

Newly, utilizing MOFs as catalysts has become a new research field [10]. The diversity of MOF topologies (i.e. pores shapes and sizes) makes MOFs attractive for a broad range of applications. The most crucial characteristic of MOFs is their high surface area. Integration of metal clusters has led to significant recovery of MOFs in porosity and stability [11]. A wide variety of MOF's structures are engineered synergistically between metal nodes, practical linkage, enclosed layers, or nanoparticles for numerous and choosy heterogeneity interplays and activates in these MOF-based nanocatalysts. The most commonly used MOFs are HKUST-1, MIL-53, Fe-BTC, UiO-66, and ZIF-8. Consequently, these materials were broadly utilized in diverse fields including drug delivery, sensing, catalyst, etc. [12,13].

In recent years, MIL structures have been used as catalyst in the Groebke-Blackburn-Bienaymé reaction (GBB reaction) [14], the Hantzsch synthesis [15,16], and the Biginelli reaction [17]. Moreover, the application of UiO-66 MOFs has been studied in Gewald condensation [18], pyrimido [4,5-d] pyrimidine synthesis [19,20], spirooxindoles synthesis [21], and dihydro-2-oxopyrroles synthesis [22].

One of the crucial subgroups of MOFs is the zeolitic imidazolate framework (ZIF) in which maximum series contain Co or Zn as the center of metal and imidazole imitative as connectors. ZIF-8 is the greater reviewed in the ZIFs toolbox massed from 2-methylimidazolen and Zn²⁺ [23]. ZIF structures have also played catalytic role in organic transmutations, like Friedel-Crafts acylation [24], Knoevenagel condensation [25], the synthesis of quinazolines [26], and the reduction of acetylenes [27]. In addition, the use of ZIFs has been expanded in industrial applications such as water purification from heavy metals and organic dyes [28,29], as well as the selective filtration of gaseous pollutants [30].

Magnetic nanoparticles, especially iron oxide, can rapidly bulk up. Therefore, covering the surface and supporting it through porous polymers, graphene derivatives, supramolecules, or even via other metals (neutral or noble) and oxides are the maximum common ways to protect gathering [31]. Magnetic nanoparticles are an important substrate for linking inorganic and organic catalysts. This can lead to major advances in the growth of different nanocatalytic systems via immobilizing homogeneous catalysts on magnetic nanoparticles. Magnetic nanoparticles can be also considered attached to organometallic frameworks, which provide the superiority of enhanced surface area and growth feedback rate [32].

One of the oxidized derivatives of graphene is graphene oxide (GO) which has a wide range of oxygen-containing useful groups including hydroxyl, carboxyl, and epoxy groups. Mixing GO with MOFs can exchange the distance among GO layers to have a variety of applications in GO/MOF catalysis, which can take advantage of the advisable assets of both kinds of materials and at the same time boost their physical properties. These composites increase the surface stability of MOFs and lead to new applications in various fields [33]. Pd–ZIF-8/rGO which have been used to catalyze the Knoevenagel condensation and reduce the resulting imine product [34]. Moreover, GO/Fe₃O₄/UiO-66-NH₂ was exploited in the optimal synthesis of chromene polycycles [35].

Recently, various nanostructures including rGO@Fe₃O₄@Ni [36], Fe₃O₄@GlcA@Ni-MOF [37], Cu-BTC@Fe₃O₄ [38], Fe₃O₄@P4VP@metal-organic framework [39], and MOF-5@SiO₂@Fe₃O₄ [40] have been used as catalyst in organic reactions. Although these reported nanocomposites have efficient catalytic activity and enjoy high stability, high surface area, high yields, and easy long-term reusability, however, intrinsic functionalities of substrates can be exploited as easy anchoring sites for nanocomponents.

Gram-negative and Gram-positive bacteria are classified based on their cell wall structure and response to Gram staining. Gram-negative bacteria such as Escherichia coli have a thin layer of peptidoglycan in their cell wall that is surrounded by an outer membrane containing lipopolysaccharides, which makes them more resistant to some antibiotics. When stained with a warm stain, they appear pink or red under the microscope. On the other hand, Gram-positive bacteria such as Staphylococcus aureus have a thick layer of peptidoglycan in their cell wall, but they lack an outer membrane, which makes them more sensitive to antibiotics, and antibiotics easily penetrate the cell wall. When stained with warm stain, they appear purple or blue under the microscope [41,42].

The incorporation of the merits of MOFs and GO to construct a novel class of composites with both enhanced functionality and large surface area is of great significance and interest. Recently, nanotechnology with a wide diversity of nanomaterials has created a new revolution in science and especially in chemical fields [[43], [44], [45], [46], [47], [48]].

This study, considering the importance of heterogeneous catalysts based on graphene oxide, ZIF-8, and magnetic nanoparticles, is intended to produce ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocomposite as a robust and reusable catalyst for the production of pyrimidine derivatives (Scheme 1). In addition, the antibacterial activities of pyrimidine derivatives were investigated via agar-well diffusion method on gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria that showed satisfactory consequences.

Scheme 1.

Synthesis of pyrimidines using ZIF-8/ZnFe₂O₄/GO-OSO₃H as catalyst.

2. Experimental

2.1. Materials and analysis

The high-purity chemicals were bought from Sigma-Aldrich and Merck. The substances with the commercial reagent grades were utilized without further purification. The melting point was unmodified and defined in a capillary tube over a melting point microscope (Boetius). ¹H NMR and ¹³C NMR spectra were attained on Bruker 250 MHz spectrometer with CDCl₃ as a solvent and TMS as an internal standard. Recording FT-IR spectra was performed on Magna-IR, spectrometer 550. Powder XRD (X-ray diffraction) was performed on a Philips diffractometer (X'pert Co.) with Cu Kα mono chromatized radiation (λ = 1.5406 Å). The microscopic morphology of the products was observed through SEM (LEO, 1455VP). The energy dispersive analysis of X-ray was used to perform compositional analysis (EDX, Kevex, Delta Class 1). A Mettler Toledo TGA was considered to perform thermogravimetric analysis (TGA) under argon, and heating was performed to 825 °C from room temperature. A Belsorp mini automatic adsorption tool was used to measure nitrogen adsorption-desorption isotherms at 196 °C followed by degassing the specimens for 5 h at 150 °C. The sample weight was estimated at 10 mg in the TG test with heating at 10 °C per minute. To analyze the magnetometer, the vibrating sample (VSM) was examined using a device (MDKFD) at room temperature.

2.2. Synthesis of graphene

In this study, graphene was prepared using graphite, KMNO₄, and H₂SO₄ via the modified Hummer's method [49].

2.3. Preparation of graphene oxide

GO was made via the modified Hummer's method, as follows: sodium nitrate (2.5 g) and graphene (5 g) were put in sulfuric acid (115 mL, 98%), and the solution was set down on a magnetic stirrer provided with a condenser put in an ice bath. In continuation, KMnO₄ (15 g) was added steadily over 120 min. The reaction mixture was then put in a water bath (35 °C) and mixed for 30 min. Then, 230 mL of deionized water was slowly poured into the vessel, and the mixture was kept at 98 °C for 15 min. To terminate the reaction, 700 mL of deionized water and H₂O₂ (50 mL, 30%) were consequently poured into the solution. When the reaction was complete, the residue was cleaned with deionized water and HCl (5%) three times. The gained GO was then dried at 60 °C for 12 h [50].

2.4. Synthesis of sulfonated GO

GO (1 g) was distributed in chloroform for 1 h and then chlorosulfonic acid was poured into the dispersed solution. The solution was then refluxed for 4 h at 60 °C in a round-bottomed flask via a cold-water condenser. Finally, the cooled suspension was filtered and washed with excess ethanol to afford sulfonated graphene oxide (Step 1, Scheme 2) [51].

Scheme 2.

The preparation steps of ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocatalyst.

2.5. Preparation of ZnFe₂O₄ nanoparticles

Initially, FeCl₃.6H₂O (0.2 M) and ZnCl₂.6H₂O (0.1 M) were dissolved individually in 75 mL of distilled water. Next, NaOH (2 M) was poured dropwise into the FeCl₃ solution till the pH of the solution reached 10. Then, the ZnCl₂ solution was added to another mixture. Next, the temperature of the reaction was increased to 80 °C for 3 h to produce a brown residue. The earned residue was washed several times with distilled water and ethanol via centrifugation, and then kept at room temperature for 24 h. Finally, ZnFe₂O₄ nanoparticles were obtained in the furnace at 500 °C for 5 h (Step 2, Scheme 2) [52].

2.6. Preparation of ZIF-8

6.5 g of 2-methylimidazole was dispersed in 80 mL of methanol. Then, Zn(NO₃)₂.6H₂O solution (0.25 M) was added to 2-methylimidazole solution under vigorous stirring at room temperature for 24 h. The obtained solid was then collected via centrifugation and washed with methanol for five times. Eventually, the achieved product dried at 75 °C under vacuum (Step 3, Scheme 2) [53].

2.7. Synthesis of ZIF-8/ZnFe₂O₄

A mixture of ZIF-8 (0.2 g) and ZnFe₂O₄ (0.1 g) was mixed in methanol (20 mL), and the mixture was placed in an autoclave at 100 °C for 24 h. The final precipitate was washed twice with DMF and methanol and then dried overnight at room temperature (Step 4, Scheme 2) [54].

2.8. Preparation of ZIF-8/ZnFe₂O₄/GO-OSO₃H

Initially, sulfonated GO (0.5 g) and ZIF-8/ZnFe₂O₄ (1.1 g) were dispersed in 30 mL of DMF. Then, it was placed in an autoclave at a temperature of 120 °C for 12 h. Afterward, the obtained sediment was washed twice with DMF and methanol. Finally, the produced ZIF-8/ZnFe₂O₄/GO-OSO₃H was dried at 40 °C for 24 h (Step 5, Scheme 2) [55].

The preparation steps of ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocatalyst are shown in Scheme 2.

2.9. The preparation method for the synthesis of pyrimidine derivatives

To synthesize pyrimidine derivatives, a mixture of 1,3-indanedione (0.5 mmol), urea (1.5 mmol), arylaldehyde (0.5 mmol), and ZIF-8/ZnFe₂O₄/GO-OSO₃H (0.005 g) was stirred in ethanol as solvent (7 mL) for about 30 min. The reaction progress was monitored by TLC (n-hexane: ethyl acetate 5: 1). After completion of the reaction, the heterogeneous catalyst was separated via a magnet, and then the resultant precipitate was filtered and recrystallized from ethanol and dried for 12 h. The spectral data of new products are shown below.

4- Cyano -3,4-dihydro-1H-indeno [1,2-d] pyrimidine-2,5-dione (4i): C₁₈H₁₁N₂0₂:¹H NMR (300 MHz, CDCl₃) δ: 5.49 (s, 1H, –CH), 7.19 (s, 1H, NH), 8.44 ppm (s, 1H, NH),7.2–8.4 (m, 8H, H_Ar); ¹³C NMR (62.9 MHz, CDCl₃) δ: 41.22, 115.28, 118.26, 123.66, 123.70, 131.83, 132.2, 132.90, 133.72, 135.88, 135.99, 136.71, 140.19, 142.55, 143.31, 188.49, 189.21; FT-IR (KBr):1589 (C C), 1693 (C O), 1724 (C O), 2225 (CN), 3437 (NH) cm⁻¹.

2- Methoxy -3,4-dihydro-1H-indeno [1,2-d] pyrimidine-2,5-dione (4j): C₁₈H₁₄N₂0₃: ¹H NMR (300 MHz, CDCl₃) δ: 3.07 ppm (s, 3H, OCH₃), 5.13 (s, 1H, CH), 7.74 (s,1H, NH), 8.44 (s, 1H, NH), 6.96–8.89 (m,8H, H_Ar); ¹³CNMR (62.9 MHz, CDCl₃) δ: 38.89, 55.79, 105.02, 110.69, 120.42, 122.05, 123.22, 128.29, 133.99, 135.05, 135.71, 135.42, 140.11, 141.43, 142.42, 160.56, 189.33, 190.68; FT-IR (KBr): 1684 (C O), 1705 (C O), 3425 (NH) cm¹.

2-Hydroxy, 4-Fluoro-3,4-dihydro-1H-indeno [1,2-d]pyrimidine-2,5-dione (4k): C₁₇H₁₁N₂0₂F: ¹H NMR (300 MHz, CDCl₃) δ: 5.75 ppm (s,1H, CH), 7.20–7.83 (m,7H, H_Ar), 9.00 (s, 1H, NH), 9.20 (1H, NH), 10.20 (1H,OH); ¹³CNMR (62.9 MHz, CDCl₃) δ: 37.7, 38.3, 112.1, 114.9, 117.1, 126.0, 129.6, 129.7, 131.2, 135.0, 137.4, 138.9, 139.3, 151.5, 154.5, 186.0; FT-IR (KBr): 1590 (C O), 1701 (C O), 3170 (NH), 3407 (OH) cm⁻¹.

2- Hydroxy, 4-Bromo-3,4-dihydro-1H-indeno [1,2-d]pyrimidine-2,5-dione (4l): C₁₇H₁₁N₂0₂Br: ¹H NMR (300 MHz, CDCl₃) δ: 5.70 ppm (s, 1H, CH), 9.00 (s, 1H, NH), 9.20 (1H, NH), 10.0 (s, 1H,OH), 7.20–7.83 (m,7H, H_Ar); ¹³CNMR (62.9 MHz, CDCl₃) δ: 37.6, 37.7, 112.1115.5, 117.1, 126.0, 129.6, 129.7, 131.2, 131.8, 134.2, 137.4, 138.9, 140.01, 154.9, 156.8, 187.0; FT-IR (KBr): 1600 (C O), 1715 (C O), 2950 (NH), 3402 (OH) cm⁻¹.

2.10. Evaluation of antibacterial activity

The antibacterial activity of the prepared products was evaluated using well diffusion method on Mueller-Hinton Agar (MHA). Inhibitory zones were reported in millimeters. S. aureus (ATCC 25923) and E. Coli (ATCC 25922) were used as references for the antibacterial assay of the products. In addition, gentamicin was used as a positive standard. Briefly, MHA plates were inoculated with a bacterial strain under aseptic conditions. All the compounds were prepared with a concentration of 512 μg/mL in the solvent and antibacterial tests of the compounds were performed according to CLSI standards [56], and incubated at 37 °C for 24 h. After the incubation period, the diameter of growth inhibition zones was measured.

3. Results and discussion

3.1. FT-IR spectroscopy

The structure of ZIF-8/ZnFe₂O₄/GO-OSO₃H was considered via FT-IR spectroscopy (Fig. 1). As shown, the peak at 3428 cm⁻¹ is due to the stretching vibration of OH groups in the structure [57]. The peak at 2923 cm⁻¹ is due to the C–H stretch of imidazole groups [58], and at 2853 cm⁻¹ stretching vibration of the C–H bond appears [59]. Moreover, the peak at 1632 cm⁻¹ corresponds to the tensile vibration of the groups of carbonyl located at the edging of GO, while the adsorption band at 1484 cm⁻¹ is due to the C N bond in the imidazole ring. In addition, the peaks at 1384 cm⁻¹, 1156 cm⁻¹ are related to the stretching vibration of C–O and S O bonds, respectively [60]. Moreover, the peaks at 757 cm⁻¹, and 616 cm⁻¹ are relevant to the Zn–N and Zn–O bonds [61], and the peak at 458 cm⁻¹ is relevant to the Fe–O.

Fig. 1.

FT-IR spectrum of ZIF-8/ZnFe₂O₄/GO-OSO₃H.

3.2. SEM analysis

Field emission scanning electron microscopy (SEM) is a useful technique for determining the size distribution of particles and porosity. The morphology and size of the ZIF-8/ZnFe₂O₄/GO-OSO₃H particles were determined using SEM are shown in Fig. 2. The results indicate that the prepared nanostructure exhibits a uniform particle shape with a particle size ranging from 71 to 85 nm (Fig. 2a and b).

Fig. 2.

The SEM images of ZIF-8/ZnFe₂O₄/GO-OSO₃H (Fig. 2a and b) with various magnifications.

3.3. BET analysis

Brunauer-Emmett-Teller (BET) analysis (Fig. 3a), adsorption/desorption (Fig. 3b), and BJH analysis (Fig. 3c) of the ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocomposite are illustrated in Fig. 3. The average diameter of the pores of the nanocatalyst is 1.21 nm, which shows the presence of porosity on the nanoscale. The analysis isotherm for ZIF-8/ZnFe₂O₄/GO-OSO₃H is more consistent with the type I adsorption isotherm, which confirms the pore volume distribution in the fine range. Also, the pore volume of the cavities in the ZIF-8/ZnFe₂O₄/GO-OSO₃H was calculated to be 1.8928 cm⁻³g⁻¹, which was constant through the literature [62].

Fig. 3.

BET analysis (a), adsorption/desorption (b), and BJH analysis (c) of ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocomposite.

3.4. EDX analysis

The chemical Purity of the samples experimented with utilizing energy-dispersive X-ray spectroscopy (EDX). Fig. 4a–b shows the EDX spectra of ZIF-8/ZnFe₂O₄ and ZIF-8/ZnFe₂O₄/GO-OSO₃H, respectively. As illustrated, ZIF-8/ZnFe₂O₄ has only O, Zn, C, and Fe elements, and in Fig. 4b the elements including Fe, Zn, O, S, and C were observed for ZIF-8/ZnFe₂O₄/GO-OSO₃H. In addition, EDX examination has been accomplished in an elemental mapping manner on ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocomposite (Fig. 5). The highly dispersed distribution of elements confirmed that there were no impurities in the produced nanocomposite. It was concluded that all of the elements including Zn (Fig. 5a), C (Fig. 5b), Fe (Fig. 5c), S (Fig. 5d), N (Fig. 5e), O (Fig. 5f), and all elements (Fig. 5g) were verified by EDX-mapping analysis. The obtained results exhibit superb purity and homogeneous dispersion. Fig. 5g illustrates the homogeneous arrangement of components all-round the structure.

Fig. 4.

EDX spectra of ZIF-8/ZnFe₂O₄ (a), and ZIF-8/ZnFe₂O₄/GO-OSO₃H (b).

Fig. 5.

EDX-Mapping of ZIF-8/ZnFe₂O₄/GO-OSO₃H; Zn (Fig. 5a), C (Fig. 5b), Fe (Fig. 5c), S (Fig. 5d), N (Fig. 5e), O (Fig. 5f), and all elements (Fig. 5g).

3.5. XRD analysis

The analysis of X-ray diffraction (XRD) for ZIF-8/ZnFe₂O₄/GO-OSO₃H is shown in Fig. 6. Diffraction peaks at 33°, 35°, and 62° are related to the crystalline structure of ZnFe₂O₄ [63]. According to the literature, the peaks at 12.5°, 18° are correspond to ZIF-8, and the related peak of GO-OSO₃H at 14° overlaps with very strong peaks related to Zn. Moreover, the presence of OSO₃H groups prevents GO peaks from appearing well. It can also be assumed that GO-OSO₃H nanosheets are grouped by ZnFe₂O₄ nanoparticles in the 20–30° section [64].

Fig. 6.

The XRD pattern of ZIF-8/ZnFe₂O₄/GO-OSO₃H.

3.6. TGA analysis

Thermogravimetric analysis (TGA) shows that the ZIF-8/ZnFe₂O₄/GO-OSO₃H sample has three weight loss regions at 100–800 °C, indicating the organometallic nature of the structure (Fig. 7). The first one at 0–100 °C is connected to the deprivation of solvents from the frame. Loss weight for the second stage is in the range of 200–500 °C, illustrating the decomposition of the structure of ZIF-8 because of the decomposition of the metal-organic framework [65]. Finally, the observed degradation at 500–800 °C can be attributed to the destruction of GO-OSO₃H [[66], [67], [68], [69]].

Fig. 7.

TGA analysis of ZIF-8/ZnFe₂O₄/GO-OSO₃H.

3.7. VSM analysis

Vibrating sample magnetometers (VSM) for ZIF-8/ZnFe₂O₄ and ZIF-8/ZnFe₂O₄/GO-OSO₃H samples are shown in Fig. 8. As observed, the saturation magnetization of ZIF-8/ZnFe₂O₄ is about 0.07 emu/g (Fig. 8a), and the saturation magnetization of ZIF-8/ZnFe₂O₄/GO-OSO₃H is 0.05 emu/g (Fig. 8b). It has been concluded that GO-OSO₃H is non-magnetic, and when it is added, the magnetic property decreases.

Fig. 8.

VSM analysis of ZIF-8/ZnFe₂O₄ (a), ZIF-8/ZnFe₂O₄/GO –OSO₃H (b).

3.8. Optimization of reaction conditions

In this research, by selecting the model reaction using 1,3-Indandione, 4 cyano-benzaldehyde, and urea, different conditions including solvents, temperatures, and catalysts were investigated. As shown in Table 1, different solvents such as H₂O, EtOH, H₂O/EtOH (1:1), DMF, CH₃CN, and PhCH₃ along with solvents-free conditions at different temperatures using ZIF-8/ZnFe₂O₄/GO-OSO₃H were evaluated. As illustrated, the best results were obtained in the attendance of ethanol as solvent under reflux conditions (Table 1).

Table 1.

The model reaction optimization in different solvents and temperatures using ZIF-8/ZnFe₂O₄/GO-OSO₃H nanocatalyst.

Entry	solvents	Temp. (°C)	Time (min)	Yielda (%)
1	–	25	240	50
2	–	70	180	60
3	–	80	180	60
4	–	100	180	70
5	H2O	70	180	65
6	CH3CN	Reflux	160	60
7	H2O	Reflux	180	60
8	EtOH	Reflux	45	98
9	DMF	Reflux	60	90
10	PhCH3	Reflux	360	45

^aIsolated Yield.

After optimizing the reaction conditions, to compare our prepared catalyst with other catalysts, the model reaction was conducted by diverse catalysts that had acidic or basic properties. The results are shown in Fig. 9. In the investigation of different catalysts, 0.01 g of each catalyst was used, and the accomplishment of the reaction was checked via TLC. The best performance corresponded to the ZIF-8/ZnFe₂O₄/GO-OSO₃H catalyst, which has several acidic sites in its structure.

Fig. 9.

The effect of various catalysts and the absence of a catalyst on the model reaction.

To evaluate the effectiveness of the catalyst, a comparison was made in the model reaction in the presence or the absence of the ZIF-8/ZnFe₂O₄/GO-OSO₃H catalyst with different amounts, including 0–0.007 g. As illustrated, the proper amount of the catalyst was 0.005 g with an efficiency of 98% yield in 45 min (Fig. 10).

Fig. 10.

The optimization of the catalyst amount for the synthesis of the corresponding pyrimidine.

In the continuation of our study, we decided to examine diverse benzaldehydes to evaluate the catalytic activity of ZIF-8/ZnFe₂O₄/GO-OSO₃H in the synthesis of pyrimidine derivatives. As expected, aryl aldehydes with electron-withdrawing groups give rise to higher yields and shorter reaction times than aldehydes with electron-donating groups (Table 2). The advantages of this research are include high efficiency, mild reaction conditions, the catalyst's reusability, and a short duration.

Table 2.

Synthesis of pyrimidine derivatives with benzaldehyde derivatives, using ZIF-8/ZnFe₂O₄/GO-OSO₃H as a catalyst

*Compounds 4i, 4j, 4k, and 4l are new products.

3.9. Reusing and recycling the catalyst

The recyclability of the ZIF-8/ZnFe₂O₄/GO-OSO₃H catalyst was investigated under the optimal conditions of the model study. As shown in Fig. 11, due to the heterogeneity and magnetic properties of the catalyst, it was simply divided from the crude via an external magnet and used for six cycles.

Fig. 11.

The reusability of ZIF-8/ZnFe₂O₄/GO-OSO₃H catalyst.

3.10. The proposed reaction mechanism

The proposed mechanism, based on the present study and previous literature [70], for the synthesis of pyrimidine derivatives catalyzed by ZIF-8/ZnFe₂O₄/GO-OSO₃H is shown in Scheme 3. It is presumed that ZnFe₂O₄ and ZIF-8 act as Lewis acids which increase the electrophilicity of the carbonyl groups of the aldehyde and 1,3-indanedione through a strong coordination bond [71,72]. The reaction proceeds via condensation of 1,3-indanedione 1 via aryl aldehyde 2 to yield intermediate I. Dehydration of the intermediate I, followed by the Michael addition of urea, led to the formation of intermediate II. In the end, the intermediate III goes through a process called intramolecular cycloaddition to make product 4.

Scheme 3.

Proposed mechanism for the synthesis of Pyrimidine derivatives using ZIF-8/ZnFe₂O₄/GO-OSO₃H.

3.11. Results of antimicrobial activities

The inhibition zone diameter was evaluated via evaluation of antimicrobial activities (Fig. 12). Antibacterial test results were included for compounds (4a-4j) by Staphylococcus aureus bacterium (Fig. 12a), and also for compounds (4a-4j) using Escherichia coli bacterium (Fig. 12b). The diameter of the inhibition zone for the synthesized pyrimidines against Staphylococcus aureus and Escherichia coli bacteria is depicted in Table 3.

Fig. 12.

The antibacterial test results including Staphylococcus aureus (a), and Escherichia coli (b) bacteria.

Table 3.

The antibacterial activities of pyrimidine derivatives.

Product	S. aureus (mm) (ATTCC-25923)	E. coli (mm) (ATTCC-25922)
4a	-	-
4b	36	–
4c	–	–
4d	-	24
4e	40	-
4f	13	-
4 g	13	23
4h	–	–
4i	15	25
4j	15	-

4. Conclusion

In this study, a reasonable synthesis method for the preparation of pyrimidine compounds using ZIF-8/ZnFe₂O₄/GO-OSO₃H as an efficient catalyst is reported. The acidic nature of the catalyst makes it more efficient and less time-consuming, with excellent yields in comparison with other catalysts. The properties of the produced heterogeneous catalyst were examined via different methods, including EDS, SEM, BET, TGA, VSM, XRD, and FT-IR analysis. The catalyst was simply retrieved and reused for six cycles without any notable loss of its catalytic activity. The antibacterial attributes of pyrimidines were considered via the agar-well diffusion technique on gram-negative (E.mcoli) and gram-positive (S. aureus) bacteria which demonstrated appropriate results. Utilization of this catalyst is suggested as a green and reasonable method for the synthesis of pyrimidine derivatives under green reaction conditions.

CRediT authorship contribution statement

Maryam Mahdavi: Methodology, Investigation, Data curation. Mohammad Ali Ghasemzadeh: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Resources, Project administration, Funding acquisition, Formal analysis, Conceptualization. Ali Javadi: Visualization, Supervision, Data curation.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.