Abstract
In this work, we report the Biginelli-type reaction between various aldehydes, acetophenones and urea systems in the presence of sulfonic acid functionalized silica (SBA-Pr-SO3H) under solvent-free conditions, which led to 4,6-diarylpyrimidin-2(1H)-ones derivatives. SBA-Pr-SO3H with a pore size of 6 nm was found to be an efficient heterogeneous solid acid catalyst for this reaction which led to high product yields, was environmentally benign with short reaction times and easy handling.
Biginelli-type reaction; green synthesis; heterogeneous SBA-Pr-SO3H catalyst
INTRODUCTION
The multi-functionalized dihydropyrimidinones (DHPMs) and dihydropyrimidines synthesis
in a Biginelli or Biginelli-like three-component-coupling reaction are of considerable
interest.11 Kappe, C. O.; Acc. Chem. Res.
2000, 33, 879.
2 Bose, D. S.; Fatima, L.; Mereyala, H. B.; J. Org.Chem.
2003, 68, 587.
3 Kappe, C. O.; Roschger, P.; J. Heterocycl. Chem.
1989, 26, 1555.
4 Karimi, B.; Mobaraki, A.; Mirzaei, H. M.; Zareyee, D.; Vali, H.;
ChemCatChem
2014, 6, 212.
5 Oliverio, M.; Costanzo, P.; Nardi, M.; Rivalta, I.; Procopio, A.;
ACS
Sustainable Chem. Eng.
2014, 2, 1228.
6 Alvim, H. G. O.; de Lima, T. B.; de Oliveira, H. C. B.; Gozzo, F. C.; de
Macedo, J. L.; Abdelnur, P. V.; Silva, W. A.; DaSilveira Neto, B. A.; ACS
Catal.
2013, 3, 1420.
7 Sahu, P. K.; Sahu, P. K.; Gupta, S. K.; Agarwal, D. D.; Ind.
Eng. Chem. Res.
2014, 53, 2085.
8 Pramanik, M.; Bhaumik, A.; ACS Appl. Mater. Interfaces
2014, 6, 933.-99 Shen, Z. -L.; Xu, X. -P.; Ji, S. -J.; J. Org. Chem.
2010, 75, 1162. In addition, it also provides an efficient access to the
corresponding pyrimidines which are found in a broad variety of biologically active
molecules and shown biological and therapeutic activities1010 Voronina, T. A.; Gordiichuk, G. N.; Andronati, S. A.; Garibova, T. L.;
Zhilina, Z. I.; Khim.-Farm, Z.; Pharm. Chem. J.
1981, 15, 495.,1111 Nagaraj, A.; Reddy, C. S.; J. Heterocycl.
Chem.
2007, 44, 1181. such as antitumoral
agents1212 Carraro, F.; Pucci, A.; Naldini, A.; Schenone, S.; Bruno, O.; Ranise,
A.; Bondavalli, F.; Brullo, C.; Fossa, P.; Menozzi, G.; Mosti, L.; Manetti, F.;
Botta, M.; J. Med. Chem.
2004, 47, 1595.
13 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.;
Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo,
C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.;
Angelucci, A.; Botta, M.; J. Med. Chem.
2007, 50, 5579.
14 Lacotte, P.; Buisson, D. -A.; Ambroise, Y.; Eur.
J. Med. Chem.
2013, 62, 722.
15 Lauro, G.; Strocchia, M.; Terracciano, S.; Bruno, I.; Fischer, K.;
Pergola, C.; Werz, O.; Riccio, R.; Bifulco, G.; Eur. J. Med. Chem.
2014, 80, 407.
16 Escande, V.; Garoux, L.; Grison, C.; Thillier, Y.; Debart, F.; Vasseur,
J. -J.; Boulanger, C.; Grison, C.; Appl. Catal., B
2014, 146, 279.-1717 Lacotte, P.; Puente, C.; Ambroise, Y.; ChemMedChem
2013, 8, 104. and HIV inhibitors.1818 Mugnaini, C.; Alongi, M.; Togninelli, A.; Gevariya, H.; Brizzi, A.;
Manetti, F.; Bernardini, C.; Angeli, L.; Tafi, A.; Bellucci, L.; Corelli, F.; Massa,
S.; Maga, G.; Samuele, A.; Facchini, M.; Clotet-Codina, I.; Armand-Ugón, M.; Esté, J.
A.; Botta, M.; J. Med. Chem.
2007, 50, 6580.,1919 Mai, A.; Artico, M.; Rotili, D.; Tarantino, D.; Clotet-Codina, I.;
Armand-Ugon, M.; Ragno, R.; Simeoni, S.; Sbardella, G.; Nawrozkij, M. B.; Samuele,
A.; Maga, G.; Este, J. A.; J. Med. Chem. 2007, 50, 5412. Some of biological
active dihydropyrimidinone compounds were represented in the Scheme 1, for example, flucytosine is an antibacterial and
antifungal active compound, monastrol is a drug which inhibit vitamin Eg5
formation, nifedipine is a Ca regulator drug utilized for blood pressure treatments, and
batzclladine B is a dihydropyrimidinone core containing natural product derived from
marines which is anti HIV virus drug.2020 Pandiarajan, K.; Chitra, S.; Tetrahedron Lett.
2009, 50, 2222.
21 Mayer, T. U.; Kapoor, T. M.; Haggarty, S.; King, R. W.; Schreiber, S.
L.; Mitchison, T. J.; Science 1999,
286, 971.
22 Boumoud, T.; Boumoud, B.; Rhouati, S.; Belfaitah, A.; Debachea, A.;
Mosset, P.; Acta Chim. Slov. 2008,
55, 617.-2323 Rovnyak, G. C.; Atwal, K. S.; Hedberg, A.; Kimball, S. D.; Moreland, S.;
Gougoutas, J. Z.; Reilly, B. C. O.; Schwartz, J.; Malley, M. F.; J. Med.
Chem.
1992, 35, 3254.
Solid acid catalysts such as ordered mesoporous materials2424 Díaz, I.; Márquez-Alvarez, C.; Mohino, F.; Pérez-Pariente, J.; Sastre, E.; J. Catal. 2000, 193, 283.,2525 Maheswari, R.; Shanthi, K.; Sivakumar, T.; Narayanan, S.; Appl. Catal., A 2003, 248, 291. have outstanding properties such as their environmental compatibility in terms of less toxicity of waste, reusability, simplicity in handling, non-corrosiveness and ease of isolation of the products in terms of heterogeneity. Thus, the surface of SBA-15 was modified by acidic functional groups (e.g., -SO3H) to prepare nano-solid acid catalyst that was gratefully used in organic synthesis.2626 Burri, D. R.; Jun, K. W.; Kim, Y. H.; Kim, J. M. Park, S. E.; Yoo; J. S.; Chem. Lett. , 2002, 212.
As mentioned in our recent studies in the application of SBA-Pr-SO3H,2727 Mohammadi Ziarani, G.; Badiei, A.; Dashtianeh, Z.; Gholamzadeh, P.;
Hosseini Mohtasham, N.; Res. Chem. Intermed.
2012, 39, 3157.
28 Mohammadi Ziarani, G.; Badiei, A.; Khaniania, Y.; Haddadpour, M.;
Iran J. Chem. Chem. Eng.
2010, 29, 1.
29 Lashgari, N.; Mohammadi Ziarani, G.; Badiei, A.; Gholamzadeh, P.;
Eur. J. Chem.
2012, 3, 310.-3030 Mohammadi Ziarani, G.; Badiei, A.; Shakiba Nahad, M.; Hassanzadeh, M.;
Eur. J. Chem.
2012, 3, 433. among different catalysts used for these Biginelli-type reactions such as
Bi(TFA)3,3131 Khosropour, A. R.; Baltork, M. I.; Ghorbankhani, H.; Catal.
Commun.
2006, 7, 713.
H2NSO3H,3232 Heravi, M. M.; Ranjbar, L.; Derikvand, F.; Alimadadi, B.; Mol.
Divers. 2008, 12,
191.
I2,3333 Ren, Y. R.; Cai, C.; Monatsh. Chem.
2009, 140, 49. nanocomposites
ZrO2-Al2O3-Fe3O4,3434 Wang, A.; Liu, X., ; Sua, Z. Jing, H.; Catal. Sci.
Technol.
2014, 4, 71. iron,3535 Zhang, L.; Zhang, Z.; Liu, Q.; Liu, T.; Zhang, G.; J. Org.
Chem.
2014, 79, 2281.,3636 Ramos, L. M.; Guido, B. C.; Nobrega, C.; Corrêa, J. R.; Silva, R. G.; de
Oliveira, H. C. B.; Gomes, A. F.; Gozzo, F. C.; DaSilveira Neto, B. A.; Chem.
Eur. J.
2013, 19, 4156. and
manganese-containing periodic mesoporous organosilica3737 Elhamifar, D.; Shábani, A.; Chem. Eur. J.
2014, 20, 3212. we used sulfonic acid functionalized silica (SBA-Pr-SO3H) as an
efficient heterogeneous catalyst to prepare
4,6-diarylpyrimidin-2(1H)-ones derivatives in excellent yields.
EXPERIMENTAL
All chemicals were obtained commercially and utilized without further purification. IR spectra were recorded from KBr disk using a FT-IR Bruker Tensor 27 instrument. Melting points were measured by using the capillary tube method with an electro thermal 9200 apparatus. The 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (250 MHz) was recorded on a Bruker DPX at 250 MHz using TMS as an internal standard. Gas chromatography-mass spectrometry (GC-MS) analysis was achieved on an Agilent 6890-5973 GC/MS detector. Also, SEM analysis was performed on a Philips XL-30 field-emission scanning electron microscope operated at 16 kV while Transmission electron microscopy (TEM) analysis was performed on a Tecnai G22 Bose, D. S.; Fatima, L.; Mereyala, H. B.; J. Org.Chem. 2003, 68, 587. F30 at 300 kV.
Preparation of SBA-15-Pr-SO3H
The modified SBA-Pr-SO3H used as a solid acid catalyst in the following reaction was synthesized and functionalized according to our previous report.3838 Kidwai, S.; Saxena, S.; Khalilur, M.; Thukral, S. S.; Eur. J. Med. Chem. 2005, 40, 816.
General procedure for the preparation of 4,6-diarylpyrimidin-2(1H)-ones derivatives (4a-4i): The SBA-Pr-SO3H (0.05 g) was activated in vacuum at 100 ºC and then cooled to room temperature. The aromatic aldehydes 1 (1 mmol), acetophenones 2 (1 mmol) and urea 3 (1 mmol), and SBA-Pr-SO3H (0.05 g) were heated at 110 ºC for the appropriated time, as mentioned in Table 2. The completion of the reaction was monitored by TLC. The mixture was cooled to room temperature, the crude product was dissolved in hot ethanol and then the catalyst was removed by filtration. Ultimately, pure crystals of compounds 4a-4i were obtained from filtrates.
4,6-Diphenyl-pyrimidin-2(1H)-one (4a): IR (KBr, νmax): 3420, 3285, 3084, 3005, 2894, 2856, 2741, 1618, 1577, 1495, 1455, 1397, 1338, 1069, 823, 681 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (250 MHz, CDCl3): δ 7.50-7.61 (m, 7H, ArH& H-5), 8.13-8.16 (m, 4H, ArH), 12.07 (s, 1H, NH). 1313 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.C NMR (100 MHz, DMSO-d6): δ 164.9, 157.0, 133.2, 132.3, 128.9, 128.0, 100.8, 56.0.3939 Hui, W.; Xiu-mei, C.; Yu, W.; Ling, Y.; Hai-qiang, X.; Hua-hong, X.; Li-ling, P.; Rui, M.; Cai-hui, Y.; J. Chem. Res. 2008, 12, 711. EI-MS: 248 (M+), 171, 94, 77.
4-(4-Chlorophenyl)-6-phenyl-pyrimidin-2(1H)-one (4b): IR (KBr, νmax): 3423, 3385, 3104, 3058, 3002, 2892, 2743, 1614, 1568, 1490, 1437, 1391, 1333, 1089, 990, 821, 765, 683 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (250 MHz, CDCl3): δ 7.49 (d, J = 7.5 Hz, 2H, ArH), 7.52-7.62 (m, 4H, ArH & H-5), 8.12 (d, J = 7.5 Hz, 2H, ArH), 8.18 (d, J = 7.5 Hz, 2H, ArH), 12.17 (s, 1H, NH). 1313 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.C NMR (100 MHz, DMSO-d6): δ 160.2, 144.9, 135.6, 129.0, 127.7, 109.6.3939 Hui, W.; Xiu-mei, C.; Yu, W.; Ling, Y.; Hai-qiang, X.; Hua-hong, X.; Li-ling, P.; Rui, M.; Cai-hui, Y.; J. Chem. Res. 2008, 12, 711. EI-MS: 282 (M+), 171, 111, 94, 77.
4-(4-Methylphenyl)-6-phenyl-pyrimidin-2(1H)-one (4c):3939 Hui, W.; Xiu-mei, C.; Yu, W.; Ling, Y.; Hai-qiang, X.; Hua-hong, X.; Li-ling, P.; Rui, M.; Cai-hui, Y.; J. Chem. Res. 2008, 12, 711. IR (KBr, νmax): 3410, 2794, 1674, 1592, 848, 773 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (400 MHz, DMSO-d6): δ 8.11-8.20 (m, 4H, ArH), 7.49-7.60 (m, 6H, ArH), 2.36 (s, 3H, CH). 1313 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.C NMR (100 MHz, DMSO-d6): δ 142.1, 131.9, 129.9, 129.3, 128.0, 128.0, 21.5;. EI-MS: 262 (M+), 247, 171, 94, 92, 77.
4-(3-Methylphenyl)-6-phenyl-pyrimidin-2(1H)-one (4d): IR (KBr, νmax): 3423, 3293, 3093, 3005, 2897, 1618, 1491, 1339, 1202, 1154, 1070, 991, 808, 774, 692 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (250 MHz, CDCl3): δ 2.39 (s, 3H, CH3), 7.49 (d, J = 7.5, 2H, ArH), 7.53-7.58 (m, 4H, ArH & H-5), 7.91-8.12 (t, 2H, ArH), 8.14 (d, J = 5.75 Hz, 2H, ArH), 12 (s, 1H, NH). EI-MS: 262 (M+), 247, 171, 94, 77.
4-(4-Hydroxyphenyl)-6-phenyl-pyrimidin-2(1H)-one (4e):3939 Hui, W.; Xiu-mei, C.; Yu, W.; Ling, Y.; Hai-qiang, X.; Hua-hong, X.; Li-ling, P.; Rui, M.; Cai-hui, Y.; J. Chem. Res. 2008, 12, 711. IR (KBr, νmax): 3331, 3300, 2928, 1659, 1616, 779 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (400 MHz, DMSO-d6): δ 11.88 (hr, s, lH, NH), 10.21 (s, lH, OH), 8.08 (m, 4H, ArH), 7.56 (d, J= 7.2 Hz, 3H, ArH), 7.42 (s, lH, ArH), 6.91 (d, J = 8.8 Hz, 2H, ArH) 1313 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.C NMR (100 MHz, DMSO-d6): δ 161.0, 131.5, 129.7, 128.9, 127.6, 115.7. EI-MS: 264 (M+), 247, 171, 94, 77.
4-(4-Methoxy-phenyl)-6-phenyl-pyrimidin-2(1H)-one (4f): IR (KBr, νmax): 3320, 3096, 1615, 1513, 809, 744 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (400 MHz, DMSO-d6): δ 8.09 (tri, 2H,ArH), 7.99 (d, J=7.6 Hz, 2H, ArH), 7.59 (d, J= 5.2 Hz, 3H, ArH), 7.39 (d, J= 8.0 Hz, 2H, ArH), 7.14 (m, lH, ArH), 2.48 (s, 3H, CH). 1313 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.C NMR (100 MHz, DMSO-d6): δ 162.3, 131.5, 129.5, 128.9, 127.7, 117.4, 55.6. EI-MS: 278 (M+), 247, 171, 108, 94, 77.
4-(Phenyl)-6-(4-Methylphenyl)-pyrimidin-2(1H)-one (4g): IR (KBr, νmax): 3436, 3280, 3096, 3005, 2901, 2745, 1616, 1512, 1459, 1338, 1180, 919, 808, 774, 691 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (250 MHz, CDCl3): δ 2.38 (s, 3H, CH3), 7.35 (d, J = 7.5 Hz, 2H, ArH), 7.51-7.58 (m, 4H, ArH & H-5), 8.05 (d, J = 7.5 Hz, 2H, ArH), 8.13 (d, J = 7.5 Hz, 2H, ArH), 12 (s, 1H, NH). EI-MS: 262 (M+), 247, 171, 94, 77.
4-(4-Chlorophenyl)-6-(4-nitrophenyl)-pyrimidin-2(1H)-one (4h): IR (KBr, nmax): 3412, 3192, 2921, 1612, 1548, 1515, 1456, 1348 cm-1. 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (300 MHz, DMSO-d6): δ 6.90-7.83 (m, 9H, ArH & H-5), 9.98 (s, 1H, NH). EI-MS: 327 (M+), 247, 171, 77.
4-(Chlorophenyl)-6-(4-Methoxyphenyl)-pyrimidin-2(1H)-one (4i):3131 Khosropour, A. R.; Baltork, M. I.; Ghorbankhani, H.; Catal. Commun. 2006, 7, 713. IR (KBr) 3429, 3 100, 289 0, 1617, 1582, 810, 600 cm-1; 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H NMR (CDCl3, 200 M Hz) d 3.8 (s, 3H, OCH3 ), 7.09 (d, J =8.4 Hz, 2H, Ar), 7.53 (s, 1H, =CH-), 7.61 (d, J = 8.09 Hz, 2H, Ar), 8.17 (m, 4H, Ar), 1 2.0 (br, 1H, NH); 1313 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.C NMR (CDCl3, 50 MHz) d 100.4, 115.1, 115.4, 128.8, 129.7, 129 .9, 130.2, 130.4, 130.7, 131.2, 137.1, 160.7, 163.0.
RESULTS AND DISCUSSION
In continuation of our interest in the developing of green methodologies and the
synthesis of diverse heterocyclic compounds of pharmaceutical importance, we report
herein the synthesis of some 4,6-diarylpyrimidin-2(1H)-ones
4a-4i derivatives under neat condition. Thus, a three-component reaction
of aromatic aldehydes 1, acetophenones 2 and urea
3, in the presence of sulfonic acid functionalized silica
(SBA-Pr-SO3H) as catalyst at 110 ºC, has been shown to give
4,6-diarylpyrimidin-2(1H)-ones derivatives 4a-4i in
excellent yields (Scheme 2). However,
3,4-dihydropyrimidin-2(1H)-ones has been prepared4040 Wang, Z. T.; Xu, L. W.; Xia, C. G.; Wang, H. Q.; Tetrahedron
Lett. 2004, 45,
7951. from the reaction of aromatic aldehydes, aromatic
ketones, and urea using a Lewis acid (FeCl36H2O-TMSCl) as
catalyst; but we did not find 3,4-dihydropyrimidin-2(1H)-ones in our
investigation. In addition, the crucial role of catalysis, solvent effects, mechanisms,
kinetics and etc. in the Biginelli reactions are discussed in the recently published
articles.4141 Alvim, H. G. O.; Lima, T. B.; de Oliveira, A. L.; de Oliveira, H. C. B.;
Silva, F. M.; Gozzo, F. C.; Souza, R. Y.; da Silva, W. A.; DaSilveira Neto, B. A.;
J. Org. Chem.
2014, 79, 3383.
42 Clark, J. H.; Macquarrie, D. J. Sherwood J.; Chem. Eur.
J.
2013, 19, 5174.
43 Medeiros, G. A.; da Silva, W. A.; Bataglion, G. A.; Ferreira, D. A. C.;
de Oliveira, H. C. B.; Eberlin, M. N.; DaSilveira Neto, B. A.; Chem.
Commun.
2014, 50, 338.
44 Souza, R. O. M. A.; da Penha, E. T.; Milagre, H. M. S.; Garden, S. J.;
Esteves, P. M.; Eberlin, M. N.; Antunes, O. A. C.; Chem. Eur. J.
2009, 15, 9799.-4545 Ramos, L. M.; Tobio, A. Y.; dos Santos, M. R.; de Oliveira, H. C. B.;
Gomes, A. F.; Gozzo, F. C.; de Oliveira, A. L.; DaSilveira Neto, B. A.; J.
Org. Chem.
2012, 77, 10184.
As can be seen in Table 1, we found that the yield of 4a improved and the reaction time was shortened when the reaction would proceed at 110 ºC under solvent free condition (entries 1-5). After optimization of the reaction condition, the generality of this method was demonstrated with respect to six different aromatic aldehydes and four acetophenones, and the results were summarized in Table 2. On the base of our investigation, we also find out that the nature of substitute groups in the aldehydes or ketones has no significant effect in this reaction. Completion of the reaction was monitored by TLC, the crude product was dissolved in hot ethanol, the heterogeneous solid catalyst was removed by simple filtration, and the pure crystals of the desired products (4a-4i) were obtained and characterize by IR, mass spectrometric analysis and 11 Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.H & 1313 Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.C NMR spectroscopic analyses. The acid catalyst can also be reused without significant loss of activity by simple washing subsequently with diluted acid solution, water and acetone.
According to proposed mechanism in Scheme 3, the condensation of aryl aldehyde 1 and urea 3 catalyzed by SBA-Pr-SO3H lead to the preparation of iminium intermediate 7 that followed by the nucleophilic addition of acetophenones 2 to give the intermediate 8, which consequently undergoes the ring closure by the nucleophilic attack of the amine onto the carbonyl group. Subsequently proton transfer, dehydration and oxidation results in the formation of adduct compound 4.
As illustrated in the Table 3, comparison of the effectiveness of various catalysts used in the synthesis of 4,6-diarylpyrimidin-2(1H)-ones derivatives is shown the advantages of current methodology. The simplicity, low reaction time and high yields of products under a green condition are resulted from the efficiency of sulfonic acid functionalized silica (SBA-Pr-SO3H) as a heterogeneous nano catalyst.
Comparison of different conditions for the synthesis of 4,6-diarylpyrimidin-2(1ff)-ones derivatives
As preparation of SBA-Pr-SO3H is illustrated in Figure 1, the calcined SBA-15 silica was functionalized with (3-mercaptopropyl) trimethoxysilane (MPTS) and then, the thiol groups were oxidized to sulfonic acid by hydrogen peroxide. Different methods such as TGA, BET and CHN methods were employed to analyze the surface of the catalyst which was demonstrated that the organic groups (propyl sulfonic acid) were immobilized into the pores.2929 Lashgari, N.; Mohammadi Ziarani, G.; Badiei, A.; Gholamzadeh, P.; Eur. J. Chem. 2012, 3, 310.
The SEM and TEM images of SBA-Pr-SO3H are illustrated in Figure 2. Uniform particles about 1 mm is shown in the SEM image (Figure 2a) as the same for SBA-15. It could be find out that morphology of solid was saved without change during the surface modification. Also, the TEM image (Figure 2b) shows the parallel channels as the pores configuration of SBA-15, indicating that the pore of modified catalyst was not collapsed. Nanopore size of SBA-Pr-SO3H act as a nano-reactor in the syntheses of 4,6-diarylpyrimidin-2(1H)-ones compounds.
CONCLUSION
In conclusion, a mild and efficient protocol for the synthesis of 4,6-diarylpyrimidin-2(1H)-ones derivatives has been developed through a one-pot Biginelli reaction under neat condition according to green chemistry using SBA-Pr-SO3H as a nano reactor with the pore size of 6 nm. In addition, the results are shown that the reaction takes place easily in the nano-pores of catalyst.4646 Mohammadi Ziarani, G.; Lashgari, N.; Badiei, A.; J. Mol. Catal. A 2015, 397, 166. The attractive features of this simple procedure are short reaction time, excellent yields, simple workup, the reusability of catalyst, and non-chromatographic purification of products.
-
SUPPLEMENTARY MATERIALThe spectral data is available in .pdf format at http://quimicanova.sbq.org.br/ with free access.
ACKNOWLEDGEMENTS
We gratefully acknowledge the financial support from the Research Council of Alzahra University and the University of Tehran.
REFERENCES
-
1Kappe, C. O.; Acc. Chem. Res. 2000, 33, 879.
-
2Bose, D. S.; Fatima, L.; Mereyala, H. B.; J. Org.Chem. 2003, 68, 587.
-
3Kappe, C. O.; Roschger, P.; J. Heterocycl. Chem. 1989, 26, 1555.
-
4Karimi, B.; Mobaraki, A.; Mirzaei, H. M.; Zareyee, D.; Vali, H.; ChemCatChem 2014, 6, 212.
-
5Oliverio, M.; Costanzo, P.; Nardi, M.; Rivalta, I.; Procopio, A.; ACS Sustainable Chem. Eng. 2014, 2, 1228.
-
6Alvim, H. G. O.; de Lima, T. B.; de Oliveira, H. C. B.; Gozzo, F. C.; de Macedo, J. L.; Abdelnur, P. V.; Silva, W. A.; DaSilveira Neto, B. A.; ACS Catal. 2013, 3, 1420.
-
7Sahu, P. K.; Sahu, P. K.; Gupta, S. K.; Agarwal, D. D.; Ind. Eng. Chem. Res. 2014, 53, 2085.
-
8Pramanik, M.; Bhaumik, A.; ACS Appl. Mater. Interfaces 2014, 6, 933.
-
9Shen, Z. -L.; Xu, X. -P.; Ji, S. -J.; J. Org. Chem. 2010, 75, 1162.
-
10Voronina, T. A.; Gordiichuk, G. N.; Andronati, S. A.; Garibova, T. L.; Zhilina, Z. I.; Khim.-Farm, Z.; Pharm. Chem. J. 1981, 15, 495.
-
11Nagaraj, A.; Reddy, C. S.; J. Heterocycl. Chem. 2007, 44, 1181.
-
12Carraro, F.; Pucci, A.; Naldini, A.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Brullo, C.; Fossa, P.; Menozzi, G.; Mosti, L.; Manetti, F.; Botta, M.; J. Med. Chem. 2004, 47, 1595.
-
13Manetti, F.; Santucci, A.; Locatelli, G. A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N. P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M.; J. Med. Chem. 2007, 50, 5579.
-
14Lacotte, P.; Buisson, D. -A.; Ambroise, Y.; Eur. J. Med. Chem. 2013, 62, 722.
-
15Lauro, G.; Strocchia, M.; Terracciano, S.; Bruno, I.; Fischer, K.; Pergola, C.; Werz, O.; Riccio, R.; Bifulco, G.; Eur. J. Med. Chem. 2014, 80, 407.
-
16Escande, V.; Garoux, L.; Grison, C.; Thillier, Y.; Debart, F.; Vasseur, J. -J.; Boulanger, C.; Grison, C.; Appl. Catal., B 2014, 146, 279.
-
17Lacotte, P.; Puente, C.; Ambroise, Y.; ChemMedChem 2013, 8, 104.
-
18Mugnaini, C.; Alongi, M.; Togninelli, A.; Gevariya, H.; Brizzi, A.; Manetti, F.; Bernardini, C.; Angeli, L.; Tafi, A.; Bellucci, L.; Corelli, F.; Massa, S.; Maga, G.; Samuele, A.; Facchini, M.; Clotet-Codina, I.; Armand-Ugón, M.; Esté, J. A.; Botta, M.; J. Med. Chem. 2007, 50, 6580.
-
19Mai, A.; Artico, M.; Rotili, D.; Tarantino, D.; Clotet-Codina, I.; Armand-Ugon, M.; Ragno, R.; Simeoni, S.; Sbardella, G.; Nawrozkij, M. B.; Samuele, A.; Maga, G.; Este, J. A.; J. Med. Chem. 2007, 50, 5412.
-
20Pandiarajan, K.; Chitra, S.; Tetrahedron Lett. 2009, 50, 2222.
-
21Mayer, T. U.; Kapoor, T. M.; Haggarty, S.; King, R. W.; Schreiber, S. L.; Mitchison, T. J.; Science 1999, 286, 971.
-
22Boumoud, T.; Boumoud, B.; Rhouati, S.; Belfaitah, A.; Debachea, A.; Mosset, P.; Acta Chim. Slov. 2008, 55, 617.
-
23Rovnyak, G. C.; Atwal, K. S.; Hedberg, A.; Kimball, S. D.; Moreland, S.; Gougoutas, J. Z.; Reilly, B. C. O.; Schwartz, J.; Malley, M. F.; J. Med. Chem. 1992, 35, 3254.
-
24Díaz, I.; Márquez-Alvarez, C.; Mohino, F.; Pérez-Pariente, J.; Sastre, E.; J. Catal. 2000, 193, 283.
-
25Maheswari, R.; Shanthi, K.; Sivakumar, T.; Narayanan, S.; Appl. Catal., A 2003, 248, 291.
-
26Burri, D. R.; Jun, K. W.; Kim, Y. H.; Kim, J. M. Park, S. E.; Yoo; J. S.; Chem. Lett. , 2002, 212.
-
27Mohammadi Ziarani, G.; Badiei, A.; Dashtianeh, Z.; Gholamzadeh, P.; Hosseini Mohtasham, N.; Res. Chem. Intermed. 2012, 39, 3157.
-
28Mohammadi Ziarani, G.; Badiei, A.; Khaniania, Y.; Haddadpour, M.; Iran J. Chem. Chem. Eng. 2010, 29, 1.
-
29Lashgari, N.; Mohammadi Ziarani, G.; Badiei, A.; Gholamzadeh, P.; Eur. J. Chem. 2012, 3, 310.
-
30Mohammadi Ziarani, G.; Badiei, A.; Shakiba Nahad, M.; Hassanzadeh, M.; Eur. J. Chem. 2012, 3, 433.
-
31Khosropour, A. R.; Baltork, M. I.; Ghorbankhani, H.; Catal. Commun. 2006, 7, 713.
-
32Heravi, M. M.; Ranjbar, L.; Derikvand, F.; Alimadadi, B.; Mol. Divers. 2008, 12, 191.
-
33Ren, Y. R.; Cai, C.; Monatsh. Chem. 2009, 140, 49.
-
34Wang, A.; Liu, X., ; Sua, Z. Jing, H.; Catal. Sci. Technol. 2014, 4, 71.
-
35Zhang, L.; Zhang, Z.; Liu, Q.; Liu, T.; Zhang, G.; J. Org. Chem. 2014, 79, 2281.
-
36Ramos, L. M.; Guido, B. C.; Nobrega, C.; Corrêa, J. R.; Silva, R. G.; de Oliveira, H. C. B.; Gomes, A. F.; Gozzo, F. C.; DaSilveira Neto, B. A.; Chem. Eur. J. 2013, 19, 4156.
-
37Elhamifar, D.; Shábani, A.; Chem. Eur. J. 2014, 20, 3212.
-
38Kidwai, S.; Saxena, S.; Khalilur, M.; Thukral, S. S.; Eur. J. Med. Chem. 2005, 40, 816.
-
39Hui, W.; Xiu-mei, C.; Yu, W.; Ling, Y.; Hai-qiang, X.; Hua-hong, X.; Li-ling, P.; Rui, M.; Cai-hui, Y.; J. Chem. Res. 2008, 12, 711.
-
40Wang, Z. T.; Xu, L. W.; Xia, C. G.; Wang, H. Q.; Tetrahedron Lett. 2004, 45, 7951.
-
41Alvim, H. G. O.; Lima, T. B.; de Oliveira, A. L.; de Oliveira, H. C. B.; Silva, F. M.; Gozzo, F. C.; Souza, R. Y.; da Silva, W. A.; DaSilveira Neto, B. A.; J. Org. Chem. 2014, 79, 3383.
-
42Clark, J. H.; Macquarrie, D. J. Sherwood J.; Chem. Eur. J. 2013, 19, 5174.
-
43Medeiros, G. A.; da Silva, W. A.; Bataglion, G. A.; Ferreira, D. A. C.; de Oliveira, H. C. B.; Eberlin, M. N.; DaSilveira Neto, B. A.; Chem. Commun. 2014, 50, 338.
-
44Souza, R. O. M. A.; da Penha, E. T.; Milagre, H. M. S.; Garden, S. J.; Esteves, P. M.; Eberlin, M. N.; Antunes, O. A. C.; Chem. Eur. J. 2009, 15, 9799.
-
45Ramos, L. M.; Tobio, A. Y.; dos Santos, M. R.; de Oliveira, H. C. B.; Gomes, A. F.; Gozzo, F. C.; de Oliveira, A. L.; DaSilveira Neto, B. A.; J. Org. Chem. 2012, 77, 10184.
-
46Mohammadi Ziarani, G.; Lashgari, N.; Badiei, A.; J. Mol. Catal. A 2015, 397, 166.
Publication Dates
-
Publication in this collection
May 2015
History
-
Received
09 May 2014 -
Accepted
22 Jan 2015