Synthesis of 3,4-dihydropyrimidinones using nano γ-Al2O3/BF3/Fe3O4 as an efficient magnetic nanocatalyst under solvent-free conditions

Bamoniri, Abdolhamid; Mirjalili, Bi Bi Fatemeh; Mahmoodi Fard Chegeni, Mahnaz

doi:10.22052/JNS.2020.04.0008

Synthesis of 3,4-dihydropyrimidinones using nano γ-Al2O3/BF3/Fe3O4 as an efficient magnetic nanocatalyst under solvent-free conditions

Document Type : Research Paper

Authors

¹ Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran

² Department of Chemistry, Faculty of Science, Yazd University, Yazd, Iran

10.22052/JNS.2020.04.0008

Abstract

Nano-γ-Al2O3/BF3/Fe3O4 magnetic nanoparticles was synthesized and characterized with Fourier Transform Infrared (FT-IR), Powder X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Transmittance Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM), Brunauer–Emmett–Teller (BET) and Thermal Gravimetry (TGA). Dihydropyrimidinones (DHP) act as antivirals, antibacterial, antifungal, antiinflammatory, antioxidan, anticarcinogen, calcium channel blockers, antihypertensive, anti-cancer and anti-HIV compounds. Nano-γ-Al2O3/BF3/Fe3O4 magnetic nanoparticles as an efficient catalyst was applied for the mild and green one-pot multicomponent synthesis of 3,4-dihydro pyrimidine-2(1H)-ones/thiones under solvent-free conditions. Biginelli reaction proceeds through an aldehyde, β-keto ester and urea or thiourea to the dihydropyrimidinone. Excellent yields of dihydropyrmidinones are gained within a short reaction time. The proposed method offers several advantages such as short reaction time, high efficiency, smooth purification, cleaning reaction, ease of recovery, and reusable catalyst. The structure and purity of these compounds were confirmed using IR and 1H NMR and 13C NMR spectral analysis. Meanwhile, the physical property of products were compared with reported ones.

Keywords

Full Text

INTRODUCTION

Magnetic nanoparticles (MNPs) have attracted great deal of attention because of unique features including good biocompatibility, low toxicity, easy preparation and functionalization, facile separation using an external magnet and a high degree of chemical stability [1-3]. Multi-component reactions (MCRs) are one of the most important processes in organic synthesis and medicinal chemistry because of their comprehensive range of applications and numerous advantages versus conventional linear type syntheses. Firstly, the Biginelli reaction was reported for the synthesis of dihydropyrimidine-2(1H)-ones via condensation reaction of acetyl acetone, benzaldehyde and urea in ethanol. Dihydropyrimidinones (DHP) have some biological activities such as antiviral, antibacterial, antifungal, antiinflammatory, antioxidant, anticarcinogen, calcium channel blockers, antihypertensive, anticancer and anti-HIV. A large number of solid acid catalysts such as lanthanum chloride [4], silica sulfuric acid [5], cellulose sulfuric acid [6], alumina sulfuric Acid [7], SbCl5.SiO2 [8], nano-TiCl4.SiO2 [9], Nano-ZrO2 sulfuric acid [10], nano- silicaphosphoricacid [11], Cu–EDTA-modified APTMS-Fe3O4@SiO2 [12], phosphomolybdic acid nanoparticles on imidazole functionalized Fe3O4@ SiO2 [13], MgFe2O4/cellulose/SO3H [14] and potassium phthalimide [15] have been utilized for the above mentioned reaction. Herein, we wish to report an efficient protocol for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones in the presence of nano-γ-Al2O3/BF3/Fe3O4 [16,17].

MATERIALS AND METHODS

Material

A commercial-grade of aliphatic diamines and 1,2-dicarbonyl compounds were purchased from Merck and Fluka chemical companies and applied without any additional purification. All other reagents were obtained from Merck and utilized as received unless otherwise noted. The course of 3,4-dihydropyrimidinones synthesis was observed by TLC on silicagel plates. FT-IR spectra of all compounds were done on a Nicolet Magna series FTIR 550 spectrometer using KBr pellets. A Bruker (DRX-400 Avance) NMR was used to record the NMR spectra. Powder X-ray diffraction (XRD) was obtained on a Philips diffractometer of X’pert company with monochromatized Cu Ka radiation (k = 1.5406 Å). FESEM was recorded on a Mira Tescan. The magnetization of the prepared catalyst was charactraized by using a Vibrating Sample Magnetometer (Meghnatis Daghigh Kavir Co. Kashan, I.R. IRAN). Sizes and morphologies of the catalyst were obtained by Philips CM120 transmission electron microscopy (TEM) and were used with a LaB6 cathode and accelerating voltage of 120 kV. Thermal gravimetric analysis (TGA) was conducted using “STA 504” instrument. Brunauer–Emmett–Teller (BET) surface area of catalyst was done with Micromeritics, Tristar II 3020 analyzer.

Preparation of Fe3O4 nanoparticles

A mixture of FeCl3.6H2O (5.838 g, 0.022 mol) and FeCl2.4H2O (2.147g, 0.011 mol) in 100 ml of distilled water was poured in a three-necked flask (250 ml) at 80°C under nitrogen atmosphere. Afterward, 10 ml of aqueous NH3 solution (32%) was added to the mixture in 30 minutes with an active mechanical stirrer. Magnetic nanoparticles were isolated from solution by a strong magnet and washed (3 times) with 200 ml of distilled water over to neutral. Finally, the products was dried at 80 °C in vacuum to form Fe3O4 nanoparticles.

Preparation of nano-γ-Al2O3/BF3

BF3.OEt2 (5 ml) was added drop-wise to a vessel which includes a mixture of nano-γ-Al2O3 (5 g) and CH2Cl2 (10 ml). The composed suspension was stirred at room temperature for 1 hour, filtered, washed with chloroform and dried at room temperature to form nano-γ-Al2O3/BF3.

Preparation of nano-γ-Al2O3/BF3/Fe3O4

Fe3O4 nanoparticles (1.5 g) were added to a mixture of nano-γ Al2O3/BF3 (1.5 g) and CH2Cl2 (40 mL) and were dispersed by ultrasonic bath for 40 minutes. Afterward, the reaction mixture was filtered, and the precipitate was washed five times with CH2Cl2 and the product was dried to form nano-γ-Al2O3/BF3/Fe3O4.

General procedure for the synthesis of 3,4-dihydropyridinone/thiones

A mixture of aldehyde (1 mmol), β-diketone or β-ketoester (1 mmol), and urea or thiourea (1.2 mmol) was stirred in oil-bath at 80 °C in the presence of nano-γ-Al2O3/BF3/Fe3O4 (0.04 g) under solvent-free conditions. After completion of the reaction, nano magnetite catalyst was separated by strong external magnet. Ethanol (2 ml) was added to remain product and then poured on crushed ice. The obtained solid product was separated by simple filtration, washed with EtOH and dried at room temperature. The resulting solid product was recrystallized from ethanol to give pure product.

Spectral Data

5-Ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidine-2(1H)-one

FTIR [ (cm-1((KBr)]: 1098 (C-O stretch.), 1232 (C-N stretch.), 1369 (CH3 bend.), 1440, 1600 (C=C aromatic stretch.), 1666 (C=O stretch.), 2979 C-H aliphatic stretch.), 3122 (=C-H stretch.), 3295 (OH stretch.), 3512 (NH stretch.). 1H NMR (DMSO-d6, 400 MHz) δ (ppm): 1.08 (t, 3H, J =7.2 Hz, CH3), 2.22 (s, 3H, CH3), 3.96 (q, 2H, J = 7.2 Hz, CH2), 5.02 (s, 1H), 6.67 (s, 2H), 7.02 (d, 2H, J = 8.0 Hz), 7.60 (s, 1H, NH), 9.09 (s, 1H, NH), 9.32 (s, 1H, OH).

5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidine-2(1H)-one

FTIR [ (cm-1((KBr)]: 1091 (C-O stretch.), 1291 (C-N stretch.), 1387 (CH3 bend.), 1420, 1463 (C=C aromatic stretch.), 1701 (C=O stretch.), 2977 C-H aliphatic stretch.), 3116 (=C-H stretch.), 3244 (NH stretch.). 1H NMR (DMSO-d6 400 MHz) δ (ppm): 1.08 (t, 3H, J = 7.2 Hz), 2.23 (s, 3H, CH3), 3.97 (q, 2H, J = 7.2 Hz), 5.13 (s, 1H), 7.22 (d, 2H, J = 7.6 Hz), 7.32 (t, 3H, J = 7.6 Hz), 7.72 (s, 1H, NH), 9.18 (s, 1H, NH).

5-Ethoxycarbonyl-6-methyl-4-(4-methoxyph-enyl)-3,4 dihydropyrimidine-2(1H)-one

FTIR [ (cm-1((KBr)]: 1090 (C-O stretch.), 1223 (C-N stretch.), 1385 (CH3 bend.), 1451, 1649 (C=C aromatic stretch.), 1705 (C=O stretch.), 2955 C-H aliphatic stretch.), 3112 (=C-H stretch.), 3242 (NH stretch.). 1H NMR (DMSO-d6 400 MHz) δ (ppm): 1.08 (t, 3H, J = 7.2 Hz), 2.22 (s, 3H, CH3), 3.70 (s, 3H, CH3), 3.96 (q, 2H, J = 7.0 Hz), 5.07 (s, 1H), 6.86 (d, 2H, J = 8.4 Hz), 7.13 (d, 1H, J = 8.4 Hz), 7.66 (s, 1H, NH), 9.14 (s, 1H, NH).

5-Methoxycarbonyl-6-methyl-4-(4-chlorophenyl)-3,4-dihydropyrimidine-2(1H)-one

FTIR [ (cm-1((KBr)]: 1093 (C-Cl), 1140 (C-O stretch.), 1235 (C-N stretch.), 1425 (CH3 bend.), 1488, 1616 (C=C aromatic stretch.), 1701 (C=O stretch.), 2927)C-H aliphatic stretch.), 3120 (=C-H stretch.), 3288 (NH stretch.). 1H NMR (DMSO-d6 400 MHz) δ (ppm): 2.11 (s, 3H, CH3), 2.27 (s, 3H, CH3), 5.23 (s, 1H), 7.23 (d, 2H, J = 8.4 Hz), 7.37 (d, 2H, J = 8.4 Hz), 7.86 (s, 1H, NH), 9.23 (s, 1H, NH).

5-Ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-dihydropyrimidine-2(1H)-thione

FTIR [ (cm-1((KBr)]: 1106 (C-O stretch.), 1177 (C-N stretch.), 1346 (CH3 bend.), 1457, 1600 (C=C aromatic stretch.), 1521 (N=O stretch.), 1690 (C=S stretch.), 2981)C-H aliphatic stretch.), 3357 (NH stretch.).1H NMR (DMSO-d6 400 MHz) δ (ppm): 1.08 (t, 3H, J = 7.2 Hz), 2.30 (s, 3H, CH3), 3.99 (q, 2H, J = 7.2 Hz), 5.29 (s, 1H), 7.47 (d, 2H, J = 8.4 Hz), 8.22 (d, 2H, J = 8.4 Hz), 9.75 (s, 1H, NH), 10.49 (s, 1H, NH).

5-Ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidine-2(1H)-thione

FTIR [ (cm-1((KBr)]: 1104 (C-O stretch.), 1179 (C-N stretch.), 1371 (CH3 bend.), 1461, 1573 (C=C aromatic stretch.), 1688 (C=S stretch.), 2975 )C-H aliphatic stretch.), 3196 (OH stretch.), 3512 (NH stretch.).1H NMR (DMSO-d6 400 MHz) δ (ppm): 1.08 (t, J =7.1 Hz, 3H, CH3), 2.26 (s, 3H, CH3), 3.98 (q, 2H, J = 7.0 Hz), 5.04 (s, 1H), 6.69 (d, 2H, J = 8.4 Hz), 6.99 (d, 2H, J = 8.4 Hz), 9.42 (s, 1H, NH), 9.54 (s, 1H, NH), 10.23 (s, 1H, OH).

RESULTS AND DISCUSSION

The XRD pattern of nano-γ-Al2O3/BF3/Fe3O4 is shown in Fig. 1. The signals at 2θ equal to 37, 45 and 67 are shown nano-γ-Al2O3 structure and the values of 2θ equal to 30.27, 35.64, 57.31 and 62.88 with FWHM equal to 0.5510, 0.3936, 0.62298 and 0.6298 respectively, show the existence of Fe3O4.

The FT-IR spectrum of Fe3O4 NPs, the wide band at 1627 and 3446 cm-1 are regarding to the H-O-H and O-H groups adsorption of Fe3O4 NPs, while the bands at 459 and 598 cm-1 are respectively corresponding to the octahedral bending and tetrahedral stretching vibration of the Fe-O functional group. Meanwhile the band at 630 cm-1 indicates the formation of Fe3O4 structure (Fig. 2a). The FT-IR spectrum of nano-γ-Al2O3/BF3/Fe3O4 shows significant bands at 1095 and 796 cm−1 corresponding to symmetrical and asymmetrical vibrations of Al–O–Al, respectively (Fig. 2b).

TG-DTA pattern of nano-γ-Al2O3/BF3/Fe3O4 was identified by heating from 0 °C to 800 °C (Fig. 3). The catalyst TGA curve suggests a preliminary weight loss of 5% below 200 °C, related to physically adsorbed water on the support. According to the TGA diagram of nano-γ-Al2O3/BF3/Fe3O4, it was exposed that the catalyst is suitable for the promotion of organic reactions until 200 °C.

The magnetization curve of magnetite nanoparticles is shown in Fig. 4 at room temperature using VSM. Within the VSM magnetization curves of nano-Fe3O4 and γ-Al2O3/BF3/Fe3O4 nanoparticles, there is a shortage of hysteresis, and the remanence and coercivity is negligible, which reveals the superparamagnetism of these nanomaterials (Fig. 4). The saturation magnetization value of nano-γ-Al2O3/BF3/Fe3O4 (28.3 emu g-1) is below that of Fe3O4 (62.3 emu g-1) because of the existence of a non-magnetic Al2O3/BF3 in catalyst.

The specific surface area of catalyst was examined by Brunauer–Emmett–Teller (BET) theory. The single point surface area is 1.3173 m2 g-1 while the mean pore diameter is 8.2525 nm and the total pore volume (P/P0=0.990) is 0.2718 cm3g-1. The N2 adsorption isotherm of catalyst is described in Fig. 5.

The FESEM and TEM images of the γ-Al2O3/BF3/Fe3O4 nanoparticles are exhibited in Figs. 6a and 6b. Using FESEM, the magnitude and morphology of the nano-γ-Al2O3/BF3/Fe3O4 was determined. They show an irregular spherical shape for nanoparticles below 5 µm.

In order to determination of dihydropyrim-idinones synthesis in the presence of nano-γ-Al2O3/BF3/Fe3O4, initially, the reaction between benzaldehyde (1 mmol), ethylacetoacetate (1 mmol) and urea (1.2 mmol), was done under various conditions (Table 1). The best result was recognized in the presence of 0.8 mg nano-γ-Al2O3/BF3/Fe3O4 at 80 °C (Table1, entry 4). The results show clearly that nanocatalyst is effective for this reaction and in the absence of the catalyst, the reaction did not take place even after long reaction time (Table 1, entry 1).

The effect of temperature was determined using doing the model reaction at various temperatures (25 °C, 60 °C and 80 °C) under solvent-free condition. The best results were obtained at 80 °C (Table 1, Entry 4). Then, the reaction was refluxed in EtOH (Table1, entry 7). It was found that, the reaction under solvent free is better than under reflux condition. Therefore, the solvent-free condition was applied for the synthesis of dihydropyrimidinones derivatives.

A comparison among nano-γ-Al2O3/BF3/Fe3O4 and other catalysts, which were reported for the synthesis of 3,4-dihydropyrimidinones. It was shown that our catalyst is better than the others in high yield and short reaction time (Table 2). According to these results, nano-γ-Al2O3/BF3/Fe3O4 led to the best outcome and created the maximum conversion in the shortest reaction time (Table 2, Entry1).

A number of aromatic aldehydes, include electron-donating and electron-withdrawing substituents were reacted with ethyl acetoacetate and urea under the improved conditions (Fig. 7).

The results are shown in Table 3. Aromatic aldehydes containing both electron-donating and electron-withdrawing groups produced high yields of the desired products. The reaction of other 1,3-dicarbonyl compounds such as acetylacetone was also operated with benzaldehyde and urea in the presence of γ-Al2O3/BF3/Fe3O4 nanoparticles in solvent-free conditions, and the corresponding dihydropyrimidinones were collected in high yields (Table 3, Entry 13). Additionally, the reaction of 4-nitro, 4-chloro and 4-hydroxy benzaldehyde derivatives were employed with ethyl acetoacetate and thiourea in the presence of above mentioned nanocatalyst at 80 °C under solvent-free condition. The related Biginelli products were achieved in high yields (Table 3, Entries 15-17).

To determine the recycling of catalyst, the reaction of 3-chlorobenzaldehyde (Table 2, Entry 3) under the improved reaction conditions was studied. After separation of the catalyst from the reaction mixture, the catalyst was washed with CH2Cl2, dried at 50 °C under vacuum for 1 h and reused for the same reaction. This method was done over five runs and all reactions led to the preferred product with high efficiency (Fig.8).

A reasonable pathway for the preparation of 3,4-dihydropyrimidinones using nano-γ-Al2O3/BF3/Fe3O4 is shown in Fig. 9. Protonation of the carbonyl group by Brønsted acid generates an electrophilic center on the carbonyl group, which is easily attacked by the urea to form intermediate (I), which is the rate-limiting step. Tracking of this intermediate (I) by β-dicarbonyl compound produces (II), which subsequently cyclizes through dehydration procedure yielding compound (III).

CONCLUSION

In conclusion, we have demonstrated a new pathway for synthesis of 3,4-dihydropyrimidinone/ thiones using nano-γ-Al2O3/BF3/Fe3O4 as an efficient solid acidic magnetic catalyst in solvent-free condition. The advantages of this process are easy work-up procedure and good to excellent yields of the final products. The catalyst was successfully recovered for five runs at least without significant loss in its activity.

ACKNOWLEDGEMENTS

The authors are grateful to University of Kashan for supporting this work by Grant No. 159189/405.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interests regarding the publication of this manuscript

References

1. Pooresmaeil M, Namazi H. β-Cyclodextrin grafted magnetic graphene oxide applicable as cancer drug delivery agent: Synthesis and characterization. Materials Chemistry and Physics. 2018;218:62-9.

2. Pooresmaeil M, Mansoori Y, Mirzaeinejad M, Khodayari A. Efficient Removal of Methylene Blue by Novel Magnetic Hydrogel Nanocomposites of Poly(acrylic acid). Advances in Polymer Technology. 2016;37(1):262-74.

3. Mansoori Y, Khodayari A, Banaei A, Mirzaeinejad M, Azizian-Kalandaragh Y, Pooresmaeil M. Fe3O4–PVAc nanocomposites: surface modification of sonochemically prepared magnetite nanoparticles via chemical grafting of poly(vinyl acetate). RSC Advances. 2016;6(54):48676-83.

4. Lu J, Bai Y, Wang Z, Yang B, Ma H. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using lanthanum chloride as a catalyst. Tetrahedron Letters. 2000;41(47):9075-8.

5. Salehi P, Dabiri M, Zolfigol MA, Bodaghi Fard MA. Silica sulfuric acid: an efficient and reusable catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Tetrahedron Letters. 2003;44(14):2889-91.

6. Reddy PN, Reddy YT, Reddy MN, Rajitha B, Crooks PA. Cellulose Sulfuric Acid: An Efficient Biodegradable and Recyclable Solid Acid Catalyst for the One-Pot Synthesis of 3,4-Dihydropyrimidine-2(1H)-ones. Synthetic Communications. 2009;39(7):1257-63.

7. Besoluk S, Kucukislamoglu M, Nebioglu M, Zengin M, Arslan M. Solvent-free synthesis of dihydropyrimidinones catalyzed by alumina sulfuric acid at room temperature. Journal of the Iranian Chemical Society. 2008;5(1):62-6.

8. Bamoniri A, Mirjalili B F, Karbasizadeh H. Nano SbCl5.SiO2: An efficient and heterogeneous catalyst for synthesis of 3,4-dihydropyrimidin-2(1H)-one(thione) derivatives under solvent-free conditions. Scientia Iranica, 2015; 22 (6):2332.

9. Zamani L, Mirjalili BBF, Zomorodian K, Zomorodian S. Synthesis and characterization of 5-substituted 1H-tetrazoles in the presence of nano-TiCl4.SiO2. South African Journal of Chemistry. 2015;68.

10. Kolvari E, Koukabi N, Hosseini MM, Vahidian M, Ghobadi E. Nano-ZrO2 sulfuric acid: a heterogeneous solid acid nano catalyst for Biginelli reaction under solvent free conditions. RSC Advances. 2016;6(9):7419-25.

11. Bamoniri A, Mirjalili B F, Nazemian S. Nano-Silica phosphoric acid: an efficient catalyst for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones (thiones) under solvent-free or sonication conditions. Iranian Journal of Catalysis, 2012; 2 (1): 17-21.

12. Sheykhan M, Yahyazadeh A, Rahemizadeh Z. Cu–EDTA-modified APTMS-Fe3O4@SiO2 core–shell nanocatalyst: a novel magnetic recoverable catalyst for the Biginelli reaction. RSC Advances. 2016;6(41):34553-63.

13. Javidi J, Esmaeilpour M, Dodeji FN. Immobilization of phosphomolybdic acid nanoparticles on imidazole functionalized Fe3O4@SiO2: a novel and reusable nanocatalyst for one-pot synthesis of Biginelli-type 3,4-dihydro-pyrimidine-2-(1H)-ones/thiones under solvent-free conditions. RSC Advances. 2015;5(1):308-15.

14. Maleki A, Jafari AA, Yousefi S. MgFe2O4/cellulose/SO3H nanocomposite: a new biopolymer-based nanocatalyst for one-pot multicomponent syntheses of polysubstituted tetrahydropyridines and dihydropyrimidinones. Journal of the Iranian Chemical Society. 2017;14(8):1801-13.

15. Kiyani H, Ghiasi M. Solvent-free efficient one-pot synthesis of Biginelli and Hantzsch compounds catalyzed by potassium phthalimide as a green and reusable organocatalyst. Research on Chemical Intermediates. 2014;41(8):5177-203.

16. Babaei E, Mirjalili BBF. One Pot Aqueous Media Synthesis of 1,3-Oxazine Derivatives Catalyzed by Reusable Nano-Al2O3/BF3/Fe3O4 at Room Temperature. Polycyclic Aromatic Compounds. 2019:1-8.

17. Babaei E, Mirjalili BBF. One-pot synthesis of five substituted tetrahydropyridines using nano-Al2O3/BF3/Fe3O4 as a highly efficient nano-catalyst. Research on Chemical Intermediates. 2018;44(5):3493-505.

18. Heravi MM, Bakhtiari K, Bamoharram FF. 12-Molybdophosphoric acid: A recyclable catalyst for the synthesis of Biginelli-type 3,4-dihydropyrimidine-2(1H)-ones. Catalysis Communications. 2006;7(6):373-6.

19. Heravi MM, Derikvand F, Bamoharram FF. A catalytic method for synthesis of Biginelli-type 3,4-dihydropyrimidin-2 (1H)-one using 12-tungstophosphoric acid. Journal of Molecular Catalysis A: Chemical. 2005;242(1-2):173-5.

20. Bigdeli MA, Jafari S, Mahdavinia GH, Hazarkhani H. Trichloroisocyanuric acid, a new and efficient catalyst for the synthesis of dihydropyrimidinones. Catalysis Communications. 2007;8(11):1641-4.

21. Shobha D, Chari MA, Mano A, Selvan ST, Mukkanti K, Vinu A. ChemInform Abstract: Synthesis of 3,4-Dihydropyrimidin-2-ones (DHPMs) Using Mesoporous Aluminosilicate (AlKIT-5) Catalyst with Cage Type Pore Structure. ChemInform. 2010;41(15).

22. Bigi F, Carloni S, Frullanti B, Maggi R, Sartori G. A revision of the Biginelli reaction under solid acid catalysis. Solvent-free synthesis of dihydropyrimidines over montmorillonite KSF. Tetrahedron Letters. 1999;40(17):3465-8.

23. Kumar A, Maurya RA. Synthesis of 3,4-dihydropyrimidin-2(1H)-ones using Ziegler–Natta catalyst system under solvent free conditions. Journal of Molecular Catalysis A: Chemical. 2007;272(1-2):53-6.