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Article

Efficient Synthesis of Dihydropyrimidines Using a Highly Ordered Mesoporous Functionalized Pyridinium Organosilica

by
Fatemeh Rajabi
1,*,
Mika Sillanpää
2,3,
Christophe Len
4 and
Rafael Luque
5,*
1
Department of Science, Payame Noor University, P.O. Box 19395-4697, Tehran 19569, Iran
2
Department of Biological and Chemical Engineering, Aarhus University, 8000 Aarhus, Denmark
3
International Research Centre of Nanotechnology for Himalayan Sustainability (IRCNHS), Shoolini University, Solan 173212, India
4
CNRS, Institute of Chemistry for Life and Health Sciences, Chimie Paris Tech, PSL Research University, 11 rue Pierre et Marie Curie, F-75005 Paris, France
5
Departamento de Química Orgánica, Campus de Rabanales, Edificio Marie Curie (C-3), Universidad de Córdoba, Ctra Nnal IV-A, Km 396, E14014 Cordoba, Spain
*
Authors to whom correspondence should be addressed.
Catalysts 2022, 12(3), 350; https://doi.org/10.3390/catal12030350
Submission received: 1 February 2022 / Revised: 7 March 2022 / Accepted: 11 March 2022 / Published: 21 March 2022 / Corrected: 26 July 2023
(This article belongs to the Special Issue Exclusive Papers of the Editorial Board Members (EBMs) of Catalysts)
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Abstract

:
A Brönsted acidic ionic solid pyridinium-functionalized organosilica network (PMO-Py-IL) was demonstrated to efficiently catalyse one-pot Biginelli condensation reaction. The green synthesis of 3,4-dihydro-2(H)-pyrimidinones (DHPMs) with high yield was carried out via one-pot three component condensation of β- dicarbonyls, aldehydes, and urea in the presence of a catalytic amount of PMO-Py-IL nanomaterial as an efficient nanocatalyst under solvent free conditions. Furthermore, the catalyst showed outstanding stability and could be easily separated and reused for at least ten reaction runs without significant loss of activity and product selectivity. The green protocol features simple set-up, cost-effectiveness, easy work-up, eco-friendly and mild reaction conditions.

Graphical Abstract

1. Introduction

3,4-Dihydro-2(H)-pyrimidinones (DHPMs) are one of the most biologically important families of nitrogen-containing heterocycles in natural and synthetic chemistry [1]. The pyrimidine ring system could be naturally found in vitamins such as thiamin, folic acid and riboflavin; nucleic acids such as uracil, thymine, and cytosine, and alkaloids such as heteromine and manzacidin [2]. DHPMs have been found to exhibit distinct pharmacological and biological activities such as being anti-tumor [3], anti-cancer [4,5], anti-inflammatory [6], anti-viral [7], anti-fungal [8], and as calcium channel blockers [9,10]. Furthermore, the industrial applications include their use as additive to agrochemicals, dyes, and organic compounds [11]. Some examples of biologically and pharmacologically active dihydropyrimidine derivatives such as [bis(2-chloroethyl)amino] pyrimidine-2,4(1H,3H)-dione (Uramustine), 5-fluoro-1-(tetrahydro-2-furyl)pyrimidine-2,4(1H,3H)-dione (Tegafur), 4-amino-1-β-darabinofuranosyl pyrimidine-2(1H)-one (Cytarabine), 5-Fluoropyrimidine-2,4(1H,3H)-dione (Fluorouracil), 1,2,3,6-Tetrahydro-2,6-dioxo pyrimidine-4-carboxylic acid (Orotic Acid), and 5-Bromo-2′-deoxyuridine-5-bromo-1-(2-deoxy-β-D-ribofuranosyl) pyrimidine-2,4-(1H,3H)-dione (Broxuridine) are shown in Figure 1.
One-pot Biginelli condensation reaction is the original procedure for the synthesis of DHPMs reported by Biginelli in 1891. This procedure involved reaction of β-dicarbonyl compounds, aromatic aldehydes, and urea under strongly acidic conditions [12,13,14,15]. Biginelli reaction was carried out by refluxing a mixture of the three components such as ethyl acetoacetate, benzaldehyde, and urea in the presence of ethanol catalyzed by hydrochloric acid which often resulted in poor to moderate yields of desired products. Due to remarkable biological and pharmacological activities and versatile use of DHPMs, the synthesis of DHPMs has been revalued. Several improved synthetic methodologies for the Biginelli condensation have recently been developed by employing various catalysts such as p-toluenesulfonic acid [16], Ni(II) coordination complex [17], chloroacetic acid [18], TiCl4 [19], RuCl3 [20], Sc(OTf)3 [21], Co(OAc)2 [22], sulfated zirconia [23], FeCl3.6H2O [24], MgBr2 [25], NbCl5 [26], Yb(OTf)3 [27], InCl3 [28], CuCl2 [29], SnCl2 [30], BF3.OEt2 [31], ZrCl4 [32], ZnCl2 [33], TMSOTf [34], CdCl2 [35], CH3SO3H [36], Iron(III) [37], SmI2 [38], Pb(NO3)3 [39], Ba(OH)3 [40], solvent-free synthesis [41], microwave irradiation [42], ultrasound radiation [43], visible light irradiation [44], Brønsted acidic ionic liquid [45], solid supported reagent [46,47,48,49,50], and enzymatic catalysts [51]. In spite of progress in the synthesis of these compounds, however, some of the previously reported procedures have significant drawbacks such as harsh reaction conditions, low product yield, use of expensive or toxic reagents, laborious workup, and large amount of toxic wastes generation. Therefore, the development of green, efficient, simple, clean, high yielding, mild, environmentally benign and cost-effective approaches using reusable catalysts is highly desirable and is of utmost importance for the synthesis of DHPMs.
The activity of the heterogeneous catalysts with various supports is dependent on the size, morphology, surface area, and nature of the support. Among them, periodic mesoporous organosilicas (PMOs) with high loading of organic functional groups, high surface area, periodically ordered and tunable pores is most favorable and have various applications such as in adsorption, catalysis, separation, medicine, and advanced materials [52,53,54,55,56,57]. –Numerous organosilane precursors can be used to successfully form PMOs via surfactant-based sol-gel technique allowing a better control of the size, structure, and composition of the PMO materials for the specific application requirements.
In continuation of our efforts towards sustainable development of highly efficient and recyclable catalysts for green chemicals synthesis [58,59,60] we have very recently developed a highly ordered porous PMO nanomaterial based on pyridinium ionic liquid as ionic solid catalyst (PMO-Py-IL), which showed excellent activity towards biodiesel production via Fischer esterification [60]. Herein, we demonstrate the application of this efficient and reusable nanocatalyst for one-pot three component Biginelli condensation reaction under mild and eco-friendly conditions.

2. Results and Discussion

The synthesis and characterization of ionic solid-acid hybrid nanomaterial with pyridinium ionic liquid framework (PMO-Py-IL) was reported according to our recently published work [60]. The growing interest towards the development of green reaction conditions has motivated us to develop 3,4-dihydro-2(H)-pyrimidinones (DHPMs) via one-pot three component condensation of β-dicarbonyls, aldehydes, and urea for further application of PMO-Py-IL nanomaterials.
The catalytic activity of PMO-Py-IL nanocatalyst has been investigated in the reaction of three-component condensation of ethyl acetoacetate, benzaldehyde and urea as a model reaction. In order to optimize the reaction conditions, the effect of different reaction parameters such as reaction time, reaction temperature, catalyst amount, and solvent were evaluated, and results are summarized in Table 1. According to the results, blank runs (in the absence of catalyst or solvent) provide a low yield of the product even after 2 h at 100 °C (Table 1, Entries 1,2). We screened the effect of solvents such as acetonitrile (CH3CN), ethanol (C2H5OH), dichloromethane (CH2Cl2), tetrahydrofuran (THF), and water (H2O) using 10 mg of the PMO-Py-IL nanocatalyst in the model reaction under reflux conditions. The excellent yield of the product was observed with C2H5OH (Entry 3), and the lowest yield was observed in CH2Cl2 (Entry 4). It was found that the reaction was carried out in excellent yield under solvent-free condition (Entry 9). Next, the effect of catalyst loading on the reaction efficacy was studied. The reaction yield was found to be significantly decreased at lower loading (Entry 10). In order to study the influence of the reaction temperature, the model reaction was carried out at different reaction temperatures (Entries 11–14). Interestingly, excellent yield of product was obtained at 50 °C. Further studies were done to optimize the reaction time. As displayed in Table 1 (Entries 15–18), it was observed that the PMO-Py-IL nanocatalyst showed the highest product yield within the short time span (of 15 min), utilizing 10 mg of the PMO-Py-IL nanocatalyst under solvent free conditions.
To evaluate the scope and limitation of the process, a series of DHPMs were synthesized via one-pot Biginelli condensation reaction under optimized conditions (Scheme 1). As shown in Table 2, various aromatic aldehydes were reacted with -dicarbonyls and urea to give desired DHPM products in high yields under optimal reaction conditions.
From the data presented in Table 2, it is clearly observed that the method was effective for both electron-withdrawing groups and electron-donating in the aromatic ring of the aldehydes. When reaction was carried out using aliphatic aldehydes such as acetaldehyde and propanal, a trace of corresponding dihydropyrimidone product was obtained even after 3 h.
To evaluate the heterogeneity of PMO-Py-IL and leaching of active species from the support, a hot filtration test was performed during the Biginelli reaction of three-component ethyl acetoacetate, benzaldehyde, and urea under optimized conditions. PMO-Py-IL nanocatalyst was removed by hot filtration after 6 min, and the filtrate solution was further left to react after catalyst filtration for 30 min. No Biginelli condensation reaction progress was observed (monitored by GC) after catalyst filtration. The results confirmed that no catalytically active species remained in the reaction solution and strong incorporation of the active sites in the organosilica framework suppressed leaching of the active phase.
In order to check the reusability and robustness of the PMO-Py-IL nanocatalyst, some studies were performed to find the lifetime and recovery factors of the nanocatalyst in the Biginelli reaction of three-component ethyl acetoacetate, benzaldehyde, and urea under optimized conditions. After ten consecutive cycles, illustrated in Scheme 1, it was found that reusable PMO-Py-IL nanocatalyst can be fully recyclable and showed outstanding structural stability maintaining the catalytic activity to around 90% of its initial activity under studied conditions. The SEM image presented in Figure 2 confirmed that the uniform cylindrical/spheroidal shape structure of porous pyridinium trifluoroacetate organosilica (PMO-Py-IL) after ten runs was similar to reported pristine PMO-Py-IL materials. Moreover, XRD analyses of PMO-Py-IL nanocatalyst before and after recycling were shown in Figure 3. The patterns are identical, and no obvious change was observed, which could be further evidence of the strong stability of the PMO-Py-IL nanocatalyst.
We further compared the catalytic performance of PMO-Py-IL nanocatalyst with reported catalysts for the synthesis of DHPMs. As can be seen in Table 3, our recoverable catalytic system possesses good activity, as compared to those of previously reported heterogeneous catalytic systems; the results obtained using the method described herein provides a more environmentally benign and economically attractive system.

3. Experimental Section

3.1. General Remarks

All solvents and chemicals were used as received without further purification. The melting points were measured with an Electrothermal model 9100 apparatus. FTIR spectra were obtained using a Shimadzu 4300 spectrophotometer. The 1H NMR and 13C NMR spectra were recorded in DMSO-d6 on Bruker DRX-300 Avance spectrometers. Proton chemical shifts (δ) were reported in ppm and were referenced to the NMR solvent (a septet centered at 39.52 ppm in 13CNMR related to DMSO-d6). The scanning electron microscope (SEM) images were produced utilizing a Jeol JSM 6490 LA field emission device with an acceleration voltage of 15 kV.

3.2. Synthesis of PMO Materials Bearing Protic Pyridinium Ionic Liquid (PMO-Py-IL)

PMO-Py-IL was synthesized following our previously reported work [60].

3.3. General Procedure for the Preparation of 3,4-dihydropyrimidin-2(1H)-Ones Using PMO-Py-IL Nanocatalyst

In a typical experiment, a mixture of aldehyde (10 mmol), 1,3-dicarbonyl compound (10 mmol), urea (12 mmol), and PMO-Py-IL nanocatalyst (10 mg) were heated at 50 °C for 15 min under stirring and solvent-free conditions. Upon reaction completion, and monitored by thin-layer chromatography (TLC), the resulting mixture was cooled to room temperature and then hot ethanol (50 °C) was added to the mixture, and the heterogeneous PMO-Py-IL nanocatalyst was separated by filtration. In order to study the reusability of the PMO-Py-IL nanocatalyst, after the first reaction run, the PMO-Py-IL nanocatalyst was separated from the reaction mixture by simple filtration. Then, the heterogeneous PMO-Py-IL nanocatalyst was washed with water and ethanol, dried in vacuum, and reused for the subsequent run. The final products were recrystallized from ethanol. All products were analyzed by 1H NMR, 13C NMR, FTIR, and melting points. The melting points of the product were matched well with literature reported data for the corresponding compounds. The spectral data of some products (4a-r) are presented below:
5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (4a): White crystal; Mp 201–203 °C; FT-IR (KBr, cm−1) ν max 3244, 3115, 2977, 1724, 1647, 1464, 1290, 1220, 1090, 781, 698. 1H NMR (DMSO-d6) δ: 1.2 (3H, t, J = 7.2 Hz, OCH2CH3), 2.24 (3H, s, CH3), 3.967 (2H, q, J = 7.2 Hz, OCH2CH3), 5.136 (d,1H, J = 3 Hz, -CH), 7.314 (m, 5H, Ar-H), 7.68 (1H, s, NH), 9.136 (1H, s, NH).13C NMR (DMSO-d6) δ: 14.5, 18.3, 54.4, 59.7, 99.7, 118.5, 126.7, 127.7, 128.9, 144.3, 149.2, 152.6, 165.8.
5-(Ethoxycarbonyl)-6-methyl-4-(4-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-one (4b): Colorless solid; Mp 210–212 °C; FT-IR (KBr, cm−1) ν max: 3235, 3118, 2976, 1727, 1648, 1610, 1462, 1391, 1214, 1091, 783, 697. 1H NMR (DMSO-d6) δ: 2.06 (3H, t, J = 7.2 Hz, OCH2CH3), 2.18 (3H, s, CH3), 2.41 (2H, q, J = 7.2 Hz, OCH2CH3), 5.23 (d,1H, J = 3.3 Hz, -CH), 7.49 (2H, d, J = 8.4 Hz, Ar-H), 7.94 (1H, s, NH), 8.08 (2H, d, J = 8.4 Hz, Ar-H), 9.29 (1H, s, NH).13C NMR (DMSO-d6) δ: 19.6, 31.1, 53.6, 109.9, 124.3, 128.1, 147.1, 149.6, 152.1, 152.5, 194.46.
5-(Ethoxycarbonyl)-4-(4-Chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4c): Yellow powder; Mp 213–215 °C; FT-IR (KBr, cm−1) ν max: 3242, 3116, 2979, 1723, 1647, 1489, 1291, 1220, 1088, 781, 492. 1H NMR (DMSO-d6) δ:1.08 (3H, t, J = 7.0 Hz, OCH2CH3), 2.46 (3H, s, CH3), 3.96 (2H, q, J = 7.0 Hz, OCH2CH3), 5.12 (1H, d, J = 2.7 Hz, -CH), 7.12–7.39 (4H, m, Ar-H), 7.72 (1H, s, NH), 9.19 (1H, s, NH). 13C NMR (DMSO-d6) δ: 14.5, 18.3, 53.9, 59.7, 99.3, 128.7, 128.9, 132.3, 144.3, 149.2, 152.4, 165.7.
5-(Ethoxycarbonyl)-6-methyl-4-(2-Chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (4e): Pale yellow powder; Mp 214–215 °C; FT-IR (KBr, cm−1) ν max: 3342, 3241, 2986, 1667, 1460, 1233, 1091,757. 1H NMR (DMSO-d6) δ:1.03 (3H, t, J = 7.0 Hz, OCH2CH3), 2.31 (3H, s, CH3), 3.91 (2H, q, J = 7.0 Hz, OCH2CH3), 5.60 (1H, s, -CH), 7.25–7.28 (1H, m, Ar-H), 7.28–7.30 (2H, m, Ar-H), 7.39–7.70 (1H, m, Ar-H), 7.71 (1H, s, NH), 9.28 (1H, s, NH).
5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4f): Pale yellow powder; Mp 201–203 °C; FT-IR (KBr, cm−1) ν max: 3322, 3126, 2937, 1720, 1670, 1434, 1276, 1215, 1075, 801, 503. 1H NMR (DMSO-d6) δ: 1.07 (3H, t, J = 7.1 Hz, OCH2CH3), 2.20 (3H, s, CH3), 3.72 (3H, s, OCH3), 3.95 (2H, q, J = 7.1 Hz, OCH2CH3), 5.23 (s, 1H, CH), 7.10 (2H, d, J = 8.1 Hz, Ar-H), 7.36 (2H, d, J = 8.1 Hz, Ar-H), 7.88 (1H, s, NH), 9.07 (1H, s, NH). 13C NMR (DMSO-d6) δ: 14.1, 18.0, 54.2, 60.4, 99.7, 121.8, 126.4, 130.3, 143.4, 146.0, 155.7, 166.3.
5-Acetyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (4m): White powder; Mp 221–223 °C; FT-IR (KBr, cm−1) ν max: 3332, 3223, 1697, 1667, 1414, 1340, 1239, 1094, 698. 1H NMR (DMSO-d6) δ: 2.062 (3H, s, CH3), 3.322 (3H, s, OCH3), 5.242 (1H, s, -CH), 7.12–7.34 (m, 5H, Ar-H), 7.771 (1H, s, NH), 9.127 (1H, s, NH). 13CNMR (DMSO-d6) δ: 19.412, 30.801, 30.837, 54.312, 110.096, 126.919, 127.842, 129.011, 144.732, 152.749, 194.774.
5-Methoxycarbonyl-6-methyl-4-(4-Nitrophenyl)-3,4-dihydropyrimidin-2(1H)one (4h): White powder; Mp 233–235 °C; FT-IR (KBr, cm−1) ν max: 3368, 3235, 3109, 2946, 1689, 1617, 1348, 1228, 1095, 855, 700. 1H NMR (DMSO-d6) δ: 2.31 (3H, s, CH3), 3.55 (3H, s, OCH3), 5.26 (1H, s, CH), 7.46 (2H, d, J = 8.6 Hz, Ar-H), 7.89(1H, s, NH), 8.19 (2H, d, J = 8.6 Hz, Ar-H), 9.36 (1H, s, NH).
5-Methoxycarbonyl-6-methyl-4-(4-Chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (4i): Yellow powder; Mp 154–156 °C; FT-IR (KBr, cm−1) ν max: 3324, 3219, 3105, 1698, 1675, 1491, 1420, 1342, 1295, 1239, 1093, 938, 700. 1H NMR (DMSO-d6) δ: 2.13 (3H, s, CH3), 3.66 (3H, s, OCH3), 5.24 (1H, s, CH), 7.03 (2H, d, J = 7.9 Hz, Ar-H), 7.35 (2H, d, J = 7.9 Hz, Ar-H), 7.88 (1H, s, NH), 9.23 (1H, s, NH). 13CNMR(DMSO-d6) δ: 14.1, 17.8, 54.9, 100.6, 122.5, 126.5, 130.3, 142.9, 146.0, 155.5, 166.7.
5-Methoxycarbonyl-6-methyl-4-(2-Chlorophenyl)-3,4-dihydropyrimidin-2(1H)one (4k): Pale yellow powder; Mp 265–268 °C; FT-IR (KBr, cm−1) ν max: 3441, 3351, 3250, 1690, 1660, 1458, 1086, 960, 800, 462. 1H NMR (DMSO-d6) δ: 2.32 (3H, s, CH3), 3.51 (3H, s, OCH3), 5.57 (1H, d, J = 3.4 Hz, CH), 7.30–7.44 (4H, m, Ar-H), 7.53 (1H, s, NH), 9.32 (1H, s, NH).
5-Acetyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (4m): White powder; Mp 231–233 °C; FT-IR (KBr, cm−1) ν max: 3268, 1702, 1675, 1599, 1493, 1236, 1106, 767, 704, 571. 1H NMR (DMSO-d6) δ: 2.09 (3H, s, CH3), 2.24 (3H, s, CH3), 5.22 (1H, d, J = 3.5 Hz, 1H), 7.17 (3H, d, J = 6.5 Hz, Ar-H), 7.22–7.34 (2H, m, Ar-H), 7.81 (1H, s, NH), 9.16 (1H, s, NH).13CNMR(DMSO-d6) δ: 18.4, 30.2, 39.6, 54.0, 109.6, 126.5, 127.4, 128.6, 144.265, 148.1, 152.2, 194.3.
5-Acetyl-6-methyl-4-(4-Nitrophenyl)-3,4-dihydropyrimidin-2(1H)-one (4n): White powder; Mp 229–230 °C; FT-IR (KBr, cm−1) ν max: 3342, 3252, 3143, 1709, 1674, 1608, 1515, 1446, 1384, 1239, 1279, 1237, 1187, 1102, 862, 763, 698. 1H NMR (DMSO-d6) δ: 2.10 (3H, s, CH3), 2.25 (3H, s, CH3), 5.24 (1H, d, J = 3.4 Hz, 1H), 7.24 (2H, d, J = 8.4 Hz, Ar-H), 7.40 (2H, d, J = 8.4 Hz, Ar-H), 7.84 (1H, s, NH), 9.21 (1H, s, NH).13CNMR(DMSO-d6) δ: 18.9, 30.5, 53.17, 109.6, 128.4, 128.6, 131.9, 143.3, 148.5, 152.1, 193.9.
5-Acetyl-6-methyl-4-(4-Chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (4o): Yellow powder; Mp 204–206 °C; FT-IR (KBr, cm −1) ν max: 3288, 3121, 2915, 1699, 1618, 1424, 1322, 1262, 1236, 1091, 837, 789, 581. 1H NMR (DMSO-d6) δ: 2.13 (s, 3H), 2.29 (s, 3H), 5.257 (d, J = 3.2 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.88 (s, 1H), 9.25 (s, 1H).
5-Acetyl-6-methyl-4-(2-Hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (4p): Pale yellow powder; Mp 204–208 °C; FT-IR (KBr, cm−1) ν max: 3240, 3096, 2982, 1682, 1603, 1584, 1503, 1173, 1113, 925, 867, 762.
5-Acetyl-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (4r): Yellow powder; Mp 172–174 °C. 1HNMR (DMSO-d6) δ: 2.073 (s, 3H), 2.275 (s, 3H), 3.72 (s, 3H), 5.19 (d, J = 3.2 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.71 (s 1H), 9.13 (s, 1H).

4. Conclusions

In summary, one-pot Biginelli condensation reaction for a series of aryl aldehydes, β-dicarbonyls and urea using protic pyridinium functionalized hybrid mesoporous materials (PMO-Py-IL) as catalyst in high yield and under solvent-free conditions was described. Moreover, the catalyst showed superior stability and could be easily separated and reused at least for ten Biginelli reaction cycles. The uniform cylindrical/spheroidal structure of porous PMO-Py-IL nanomaterial was confirmed by the SEM image of the PMO-Py-IL nanomaterial after ten reaction runs. The ultimate goal of present work was the development of a cost-effective, green, sustainable, reusable, and simple and mild process for synthesis of 3,4-dihydro-2(H)-pyrimidinones (DHPMs).

Author Contributions

F.R. and R.L. conceived the study, contributed with characterization and writing of the manuscript; F.R. performed the experiments; M.S. and C.L. contributed with the useful advice and editing the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Data is contained within the article.

Acknowledgments

F.R. is grateful to Payame Noor University for partial support of this work.

Conflicts of Interest

The authors declare no conflict of interest.

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Catalysts 12 00350 g001 550
Figure 1. Chemical structures of some biologically and pharmacologically active DHPMs.
Figure 1. Chemical structures of some biologically and pharmacologically active DHPMs.
Catalysts 12 00350 g001
Catalysts 12 00350 sch001 550
Scheme 1. PMO-Py-IL catalyzed the one-pot Biginelli condensation reaction.
Scheme 1. PMO-Py-IL catalyzed the one-pot Biginelli condensation reaction.
Catalysts 12 00350 sch001
Catalysts 12 00350 g002 550
Figure 2. SEM image of the fresh PMO-Py (left) and recycled PMO-Py-IL after ten runs (right).
Figure 2. SEM image of the fresh PMO-Py (left) and recycled PMO-Py-IL after ten runs (right).
Catalysts 12 00350 g002
Catalysts 12 00350 g003 550
Figure 3. XRD patterns corresponding to the fresh PMO-Py-IL (left) and recycled PMO-Py-IL after ten runs (right).
Figure 3. XRD patterns corresponding to the fresh PMO-Py-IL (left) and recycled PMO-Py-IL after ten runs (right).
Catalysts 12 00350 g003
Table
Table 1. Effect of different parameters on the Biginelli reaction of ethyl acetoacetate (10 mmol), benzaldehyde (10 mmol), and urea (12 mmol).
Table 1. Effect of different parameters on the Biginelli reaction of ethyl acetoacetate (10 mmol), benzaldehyde (10 mmol), and urea (12 mmol).
EntryPMO-Py-IL
(mg)		SolventTemp.
(°C)		Time
(min)		Yield
(%) a
1 - - 10012020
2 - C2H5OHReflux12028
310C2H5OHReflux12095
410CH2Cl2Reflux12042
510THFReflux12054
610H2OReflux12082
810CH3CNReflux12058
910 - 8012099
108 - 8012088
1110 - 7012084
1210 - 6012087
1310 - 5012099
1410 - 4012070
1510 - 506098
1610 - 503098
1710 - 501598
1810-501091
a Isolated yields.
Table
Table 2. Synthesis of dihydropyrimidones catalyzed by PMO-Py-IL nanocatalyst under solvent free conditions.
Table 2. Synthesis of dihydropyrimidones catalyzed by PMO-Py-IL nanocatalyst under solvent free conditions.
EntryR1R2ProductYield (%) aM.P(°C) [Ref.]
1C6H5OEt4a98201–203 [16]
24-NO2-C6H4OEt4b94211–213 [16]
34-Cl-C6H4OEt4c92210–212 [16]
42-OH-C6H4OEt4d80217–219 [16]
52-Cl-C6H4OEt4e82220–223 [16]
64-OCH3-C6H4OEt4f84201–203 [16]
7C6H5OMe4g96221–223 [16]
84-NO2-C6H4OMe4h92233–235 [16]
94-Cl-C6H4OMe4i85154–156 [16]
102-OH-C6H4OMe4j78243–244 [45]
112-Cl-C6H4OMe4k82249–252 [16]
124-OCH3-C6H4OMe4l80232–233 [16]
13C6H5Me4m98231–233 [45]
144-NO2-C6H4Me4n93229–230 [45]
154-Cl-C6H4Me4o90204–206 [45]
162-OH-C6H4Me4p82215–217 [45]
172-Cl-C6H4Me4q85201–203 [45]
184-OCH3-C6H4Me4r84172–174 [45]
a Isolated yield.
Table
Table 3. Comparison of catalytic activities in the Biginelli condensation reaction of benzaldehyde, ethyl acetoacetate, and urea using heterogeneous catalysts under solvent-free conditions.
Table 3. Comparison of catalytic activities in the Biginelli condensation reaction of benzaldehyde, ethyl acetoacetate, and urea using heterogeneous catalysts under solvent-free conditions.
EntryCatalystT (°C)TimeConversion (%)Ref.
1PMO-Py-IL (0.002 g)5015 min98This work
2Cu@SBA-15 (0.01 g)1005 min94[50]
3TSA/bent (0.09 g)805 h86[61]
4TSILS (ionic liquids)9010 min94[62]
5PTA@MIL-101 (0.6 mol%)10060 min90[63]
6PMo7W5/kaolin (20%)1008 min95[64]
7β-Cyclodexterin (0.5 mol%)100180 min85[65]
8NH4H2PO4/MCM-41 (0.04 g)1006 h72[66]
940% w/w WSi/A-15 (0.05 g)924.588[67]
10Nano-γ-Al2O3/BF3/Fe3O4 (0.008 g)8030 min95[68]
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Rajabi, F.; Sillanpää, M.; Len, C.; Luque, R. Efficient Synthesis of Dihydropyrimidines Using a Highly Ordered Mesoporous Functionalized Pyridinium Organosilica. Catalysts 2022, 12, 350. https://doi.org/10.3390/catal12030350

AMA Style

Rajabi F, Sillanpää M, Len C, Luque R. Efficient Synthesis of Dihydropyrimidines Using a Highly Ordered Mesoporous Functionalized Pyridinium Organosilica. Catalysts. 2022; 12(3):350. https://doi.org/10.3390/catal12030350

Chicago/Turabian Style

Rajabi, Fatemeh, Mika Sillanpää, Christophe Len, and Rafael Luque. 2022. "Efficient Synthesis of Dihydropyrimidines Using a Highly Ordered Mesoporous Functionalized Pyridinium Organosilica" Catalysts 12, no. 3: 350. https://doi.org/10.3390/catal12030350

APA Style

Rajabi, F., Sillanpää, M., Len, C., & Luque, R. (2022). Efficient Synthesis of Dihydropyrimidines Using a Highly Ordered Mesoporous Functionalized Pyridinium Organosilica. Catalysts, 12(3), 350. https://doi.org/10.3390/catal12030350

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