In recent decades, magnetic nanoparticles (MNPs) have been widely studied for various biological and medical applications [1, 2]. They have been shown to be promising supports for the immobilization of catalysts because magnetic catalysts can be easily separated from the reaction medium by an external magnet, which provides a simple separation of the catalyst without the need for filtration, centrifugation, or other tedious workup processes [3]. This separation technique has a special importance for nano-sized catalyst supports where filtration methods result in the loss of catalyst particles and product contamination. Apart from an easy separation, an interesting property of MNPs is that an appropriate surface modification provides a wide range of magnetic-functionalized catalysts that show equal and sometimes higher activity than their homogeneous catalysts in organic transformations. In recent years, MNPs as catalyst or catalyst support have been widely used in a variety of important organic reactions including C-C coupling [4, 5, 6], reduction [7, 8, 9], oxidation [10, 11, 12, 13, 14, 15] and multicomponent reactions [16, 17, 18, 19] with high activity.
Recently, Wang et al. [20] reported the synthesis of silica coated Fe3O4 MNPs for immobilizing heteropoly acids (HPAs) with a Keggin structure (tungstophosphoric acid). Their synthesized catalyst was a magnetically separable catalyst and after completion of the reaction, it was easily separated by an external magnet. Rafiee et al. [21, 22, 23] reported another silica coated MNPs with the formula Fe2O3@SiO2 for supporting tungstophosphoric acid and phosphomolybdic acid. They showed good catalytic activity by these catalysts. In addition to Fe3O4 and Fe2O3, there are other iron oxides with the ferrite structure and general formula (AFe2O4), where A can be Mn, Co, Ni, Cu, and Zn [24, 25, 26]. Ni ferrites (NiFe2O4) are one of the most versatile magnetic materials with a high saturation magnet ization, high Curie temperature, chemical stability, and relatively high permeability [27], and because of these magnetic properties it can be used as a magnetic source.
The Preyssler HPA (H14NaP5W30O120) is a HPA which has significant advantages, such as 14 acidic protons, high thermal stability, high hydrolytic stability (0 < pH < 12), regenerability and safety [28, 29]. Owing to the low surface area (7-10 m2/g) and high solubility of HPAs in polar solvents, it is preferrable to use them in supported form. These catalysts can be supported on neutral solids, such as silica, activated carbons, or zeolites and acidic ion exchange resins [29, 30]. Recently, we supported Preyssler HPA on silica and used this supported catalyst for various reactions [29, 31, 32, 33]. Several advantages of using supported HPAs compared to the homogeneous catalyst include easier recovery and recycling after reaction and easier product separation [34]. However, the separation and recovery of the immobilized Preyssler on silica is usually performed by filtration or centrifugation, which are not eco-friendly processes. The immobilization of this HPA on silica-coated MNPs with a new structure (NiFe2O4) can be employed to develop a novel heterogeneous catalyst system which is magnetic that possesses both a high separation efficiency and a relatively high surface area to maximize catalyst loading and activity.
In a continuation of our achievements in the preparation of novel catalysts [35, 36, 37, 38] and based on our previous success in the preparation of MNPs as catalysts [39, 40, 41], in this study, we supported Preyssler HPA on NiFe2O4@SiO2 (denoted NFS-PRS). After the characterization of this novel magnetically recoverable catalyst, its catalytic activity was tested in the synthesis of bis(dihydropyrimidinone)benzene and 3,4- dihydropyrimidin- 2(1H)-ones and -thiones derivatives by the Biginelli reaction. The synthesis of these products occurred from the condensation of terephthalic aldehyde, urea and 1,3-dicarbonyl compound. This is a simple, green, and efficient synthesis method with these reactions using NFS-PRS as a heterogeneous and highly active acidic catalyst (Scheme 1).
All reagents were purchased from Merck and Aldrich and used without further purification. Melting points were determined on an Electrothermal Type 9100 melting point apparatus. The particle size and morphology of the synthesized catalyst were characterized with a transmission electron microscope (TEM, Philips CM-200 and Titan Krios) and scanning electron microscope (SEM, Philips XL 30 and S-4160) with a gold coating. X-ray diffraction (XRD) measurements were performed using a Bruker AXS Company, D8 ADVANCE diffractometer (Germany). Infrared (IR) spectra were recorded on a Thermo Nicolet AVATAR-370 FT-IR spectrophotometer and 1H NMR spectra were recorded on a Bruker DRX400 spectrometer.
The core-shell silica nickel ferrite (NFS, Fig. 1) was synthesized according to our previous reports [39, 40, 41]. Afterwards, for the immobilization of Preyssler HPA on the NFS, 0.75 g of Preyssler was dissolved in 5 mL of water. This solution was added dropwise to a suspension of 1.0 g of NFS in water (50 mL). The mixture was stirred for 12 h at room temperature under vacuum. After stirring for the specified time, the solvent was evaporated off and the supported catalyst collected by a permanent magnet and dried in a vacuum overnight. After the drying, the supported nano catalyst was calcined at 250 °C for 2 h [31].
The NFS-PRS catalyst (0.02 g) was added to a solution of terephthalic aldehyde (1.0 mmol), urea (2.5 mmol) and 1,3-dicarbonyl compound (2.0 mmol) in ethanol (10 mL) and refluxed for 45-60 min. Upon completion, the reaction mixture was allowed to cool to room temperature and the NFS-PRS was separated from the reaction mixture by an external magnet and thoroughly washed and dried to be reused in the next run. Cold water (20 mL) was added to the reaction mixture (without a catalyst) and after stirring for a few minutes, the solid product formed was filtered off and washed several times with cold ethanol and water. The resulting crude product was recrystallized from ethanol and gave compounds 5a-5h in high yields.
Diethyl-4,4'-(1,4-phenylene)bis(6-methyl-2-oxo-1,2,3,4- tetrahydropyrimidine-5-carboxylate) (5b). 1H NMR(400 MHz, DMSO-d6): δ 1.0 (6H, t, J = 7.2 Hz, OCH2CH3), 2.23 (6H, s, CH3), 3.9 (4H, q, J = 7.3 Hz, OCH2CH3), 5.1 (2H, d, J = 3.2 Hz, CH), 7.17 (4H, s, Ph), 7.69 (2H, s, NH), 9.17 (2H, d, J = 1.6 Hz, NH); IR (KBr, cm-1): υ 3365, 3239, 3104, 2971, 1701, 1647, 1459, 1223, 1084; MS (m/z): 442 (M+), 255, 236, 149, 124, 97, 83, 69, 57; Anal. Calcd.: C, 59.72; H, 5.92; N, 12.66. Found: C, 59.58; H, 5.94; N, 12.71.
4,4'-(1,4-phenylene)bis(5-acetyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one) (5c). 1H NMR (400 MHz, DMSO-d6): δ 2.07 (6H, s, CH3), 2.37 (6H, s, COCH3), 5.1 (2H, d, J = 3.6 Hz, CH), 7.18 (4H, s, Ph), 7.71 (2H, s, NH), 9.1 (2H, d, J = 1.6 Hz, NH); IR (KBr, cm-1): υ 3423, 3284, 1686, 1655, 1610, 1577, 1184, 1109, 1018; MS (m/z): 382 (M+), 369, 301, 236, 97, 83, 69, 57.
4,4'-(1,4-phenylene)bis(5-benzoyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one) (5d). 1H NMR (400 MHz, DMSO-d6): δ 1.65 (6H, s, CH3), 5.20 (2H, d, J = 3.2 Hz, CH), 7.13 (4H, s, Ph), 7.3-7.5 (10H, m, COPh), 7.76 (2H, s, NH), 9.15 (2H, s, NH); IR (KBr, cm-1): υ 3400, 3096, 1685, 1417, 1179.
4,4'-(1,4-phenylene)bis(5-acetyl-6-(trifluoromethyl)-3,4-dihydropyrimidin-2(1H)-one) (5e). 1H NMR (400 MHz, DMSO-d6): δ 2.03 (6H, s, CH3), 5.14 (2H, d, CH), 7.31 (4H, s, Ph), 7.76 (2H, s, NH), 9.48 (2H, s, NH); IR (KBr, cm-1): υ 3412, 3101, 1680, 1415, 1159.
Similar to the above synthesis method, NFS-PRS catalyst (0.02 g) was added to a solution of aromatic aldehyde (1.0 mmol), urea (1.2 mmol) and 1,3-dicarbonyl compound (1.0 mmol) in ethanol (10 mL) and refluxed for 15-30 min. Upon completion, the reaction mixture was allowed to cool to room temperature and the NFS-PRS was separated from the reaction mixture by an external magnetic field and thoroughly washed and dried to be reused in the next run. Cold water (40 mL) was added to reaction mixture (without a catalyst) and after stirring for a few minutes, the solid product formed was filtered off and washed several times with cold ethanol and water. The resulting crude product was recrystallized from ethyl acetate/ n-hexane and gave compounds (6a-6h) in high yields.
The NFS-PRS catalyst was prepared by the route outlined in Fig. 1. Magnetic NiFe2O4 nanoparticles were prepared by the chemical method and subsequently were coated with tetraethyl orthosilicate to get silica coated nickel ferrite nanoparticles (NFS). Finally, the Preyssler HPA was supported on the silica coated MNPs to give the corresponding Preyssler HPA supported on the magnetic nanoparticles (NFS-PRS). The catalyst was characterized by FT-IR, TEM and particle size analysis, SEM and EDS, XRD and VSM.
TheFT-IR spectra of NFS, Preyssler and NFS-PRS are shown in Fig. 2. NFS exhibited highly intense absorption peaks at 1200 and 1100 cm-1. These peaks are assigned to the longitudinal and transverse stretching vibration modes of the Si-O-Si asymmetric bond. Additional bands at 812 and 470 cm-1 were identified as the characteristic peaks of the Si-O-Si bond. The other peak observed at 950 cm-1 assigned to the SiO32- vibrations indicated the existence of nonbridging oxygen ions [29, 31]. Preyssler HPA displayed vibrations at 1162, 1090, and 1025 cm-1 for the P-O stretching in the Preyssler structure, 980 and 906 cm-1 for W-O-W stretching, 802 cm-1 for W=O stretching, and 522 cm-1 for P-O bending [42]. There was also a highly intense absorption peak at 1630 cm-1, which was attributed to adsorbed water [20]. In the NFS-PRS, the peaks in the regions of 3563, 1090, 960, 913, 794, and 566 cm-1 confirmed the successful immobilizing of the Preyssler HPA on the surface of the silica coated nickel ferrite NPs.
Fig. 3 shows TEM images of the synthesized NFS and NFS-PRS MNPs. In the NFS-PRS, the darker parts proved good immobilizing of Preyssler HPA on the NFS. Also, the particle size distribution (Fig. 3(c)) of the NFS NPs showed that these MNPs have a size between 25 to 97 nm and a mean diameter of 53 nm. The morphological features were examined by SEM. The SEM images before (Fig. 4(a)) and after (Fig. 4(b)) supporting Preyssler HPA on the NFS demonstrated that these MNPs were almost spherical and regular in shape. However, aggregation of the nanoparticles was found. This aggregation may have occurred during the coating and supporting process. In the energy dispersive spectrum (EDS) of NFS-PRS (Fig. 4(c)), the tungsten peaks confirmed the successful immobilizing of the Preyssler HPA on the surface of the silica coated nickel ferrite MNPs. These observations were in agreement with the FT-IR results.
In our previous work [40], we supported HPAs with Keggin structures on silica coated NiFe2O4. The structure of these MNPs before and after the supporting were compared using XRD analysis. We showed that there was no separate crystal phase that was characteristic of a Keggin HPA in the supported form. The broad peak at 2θ = 20°-30° that appeared was related to the amorphous silica phase in the shell of NiFe2O4 [43]. In the XRD pattern of NFS-PRS (Fig. 5), the characteristic peaks at 2θ = 30°, 35°, 43°, 54° 57, and 63° were similar to the previously reported data for NiFe2O4 MNPs [44, 45], and the broad peak at 2θ = 20°-30° can be assigned to an amorphous silica phase in the shell of NiFe2O4. Similar to our previous work, there was no characteristic peak of the Preyssler HPA in the XRD pattern [20]. These observations indicated that the Preyssler HPA was well dispersed on the surface of the silica coated MNPs since there was no crystalline phase of this HPA detected by XRD analysis.
It is important that the core/shell material possess sufficient magnetic and superparamagnetic properties for practical applications. Magnetic hysteresis measurements for the NiFe2O4 were done in an applied magnetic field at room temperature with the field swept from −10000 to +10000 Oe. As shown in Fig. 6, the M (H) hysteresis loop for the samples was reversible, showing that the nanoparticles exhibit superparamagnetic characteristics. The hysteresis loops of these reached saturation at the maximum applied magnetic field. The magnetic saturation value of NiFe2O4 was 16.71 emu/g at room temperature. These MNPs showed high permeability in magnetization and their magnetization was sufficient for easy magnetic separation with a normal magnet.
Initially, in order to optimize the reaction conditions, the synthesis of compound 5b was used as a model reaction. A mixture of terephthalic aldehyde (1.0 mmol), urea (2.5 mmol) and ethyl acetoacetate (2.0 mmol) in the presence of NFS-PRS was heated in different solvents and under a solvent-free condition to assess the effect of the solvent on the reaction yield. As shown in Table 1, the yield of the reaction under ethanol reflux condition was higher and the reaction time was shorter than with the other solvents and solvent-free condition (entry 7). Increasing the reaction time did not increase the yield significantly (entry 8). The model reaction was carried out in the presence of silica-supported Preyssler HPA (SiO2-PRS) and Preyssler HPA. The yield of the reaction after the same time and condition was lower than when we used NFS-PRS as a catalyst (entries 8 and 9). We believe that when we used Preyssler HPA in the supported form, due to the adsorption of the reactants on the surface of the catalyst, there was an increase in the local concentration of reactants around the active sites of the NFS-PRS which promoted the reaction effectively. This reaction was also carried out in presence of other HPAs with Keggin structures. These HPAs were not efficient for this reaction and the yields of the reaction were very low (entries 10−12).
Next, to determine the optimum quantity of NFS-PRS, the reaction of terephthalic aldehyde, urea and ethyl acetoacetate was carried out under the above conditions using different amounts of catalyst (Table 2). No product was obtained in the absence of the catalyst (entry 1), indicating that the catalyst was necessary for the reaction. Increasing the amount of the catalyst increased the yield of the product 5b (entries 2 and 3). The use of 0.02 g of catalyst resulted in the highest yield in 45 min (entry 4). Increasing the amount of the catalyst beyond this value did not increase the yield noticeably (entries 5 and 6).
Finally, after optimization of the reaction conditions, we prepared a range of bis(dihydropyrimidinone)benzene derivatives (Table 3). In all cases, 1,3-dicarbonyl compounds with substituents carrying either electron-donating (entries 1−4) or electron-withdrawing (entry 5) groups reacted successfully and gave the expected products in good to excellent yields and short reaction times. Also, thiourea has no significant effect on the reaction time and yield (entries 6−8). In addition, we synthesized 3,4-dihydropyrimidin-2(1H)-ones and -thiones under the optimized reaction conditions. It can be seen that by using this magnetic acidic catalyst, aromatic aldehydes containing electron-donating and electron-withdrawing groups (entries 9-16) afforded the products with good to excellent yields, and different aldehydes have no significant effect on the reaction time and yield.
To show the merit of the present catalyst, we compared the results of using NFS-PRS in the synthesis of 3,4- dihydropyrimidin-2(1H)-ones from benzaldehyde, urea and ethyl acetoacetate with other heterogeneous catalysts like H4SiW12O40 heteropoly acid [49], zinc hydrogen sulfate Zn(HSO4)2 [50], P2O5-SiO2 [51] and silica-bonded S-sulfonic acid (SBSSA) [52]. All the catalysts were tested at the same catalyst loading. As shown in Table 4, NFS-PRS (entry 5) was the most efficient catalyst and gave high yields of product in shorter reaction times. In addition, the advantages of NFS-PRS are its recyclability and very simple work-up.
A mechanism for the condensation of terephthalic aldehyde, urea and 1,3-dicarbonyl compounds in the presence of NFS-PRS for the synthesis of bis(dihydropyrimidinone)benzene is shown in Scheme 2.
From the viewpoint of green chemistry, good recovery and reusability of the catalyst are highly preferred. To show this, the same model reaction was again studied under the optimized conditions. After the completion of the reaction, NFS-PRS was separated from the reaction mixture by a magnet and thoroughly washed with methanol and chloroform to remove residual product. It was dried at 100 °C under vacuum for 2 h and reused for the reaction. As shown in Fig. 7, the catalyst can be reused at least five times without loss of activity.
The FT-IR spectra of the NFS-PRS catalyst before use (fresh) and after reuse for five times (recovered) were obtained. As shown in Fig. 8, the FT-IR spectrum of the recovered NFS-PRS showed that the structure of the catalyst remained the same after five runs. In addition, the weight of the recovered catalyst was the same as the amount of the fresh catalyst used the first time in the reaction.
We have prepared a novel magnetic catalyst containing Preyssler HPA supported on silica coated nickel ferrite NPs (NFS-PRS) for the synthesis of bis(dihydropyrimidinone) benzene and 3,4-dihydropyrimidin-2(1H)-ones and -thiones derivatives by the Biginelli reaction. The Preyssler HPA provided adequate acidic sites to give the excellent catalytic activity of NFS-PRS. This magnetic catalyst can be easily removed from the reaction mixture by an external magnet, and it was reused several times without loss of catalytic activity. In addition to the synthesis of these products by the Biginelli reaction, the environmentally benign NFS-PRS catalyst is potentially promising for other acid-catalyzed chemical reactions.
The authors are thankful to Ferdowsi and Islamic Azad University, Mashhad and Bandar Abbas Branches for financial support.
2015, Vol. 36 Issue (3): 299-307
PDF (1028 KB)
2015, Vol. 36 Issue (3): 299-307
PDF (1028 KB)