Synthesis of 3,4-dihydropyrimidin-2(1H)-one and 3,4-dihydropyrimidin-2(1H)-thione derivatives from aldehydes, 1,3-dicarbonyl derivatives and urea or thiourea using granite and quartz as new, natural and reusable catalysts. Some of the 3,4-dihydropyrimidin-2(1H)-thione derivatives were used to prepare new heterocyclic compounds. The antimicrobial activity of selected examples of the synthesized compounds was tested and showed moderate activity. 1. Introduction Aryl-3,4-dihydropyrimidines derivatives have recently received great attention because of their wide range of therapeutic and pharmacological properties, such as antiviral [1], antitumor, antibacterial and antifungal [2], anti-inflammatory [3], antihypertensive agents, and neuropeptide Y (NPY) antagonists [4]. Furthermore, these compounds have emerged as the integral backbones of several calcium-channel blockers [5]. Also, several alkaloids containing the dihydropyrimidine were isolated from marine sources, for example, of these are the batzelladine alkaloids, which are found to be potent HIVgp-120-CD4 inhibitors [6, 7]. In general, the classic Biginelli approach to 3,4-dihydropyrimidinones is based on the condensation of ethyl acetoacetate, aromatic aldehyde, and urea under strong acidic conditions; this suffers, however, from low yields of products, particularly in case of substituted aromatic and aliphatic aldehydes [8, 9]. This problem has led to the development of multistep synthetic strategies that produce relatively higher yields, but lack the simplicity of the original one-pot-Biginelli protocol. Thus, the Biginelli reaction has received renewed interest from researchers interested in discovering milder and more efficient procedures that are applicable to a wide range of substituents in all three components and proceed in better yields. So, the one-pot-Biginelli protocol for 3,4-dihydropyrimidines synthesis was explored by varying all components and catalysts [10–18] in protic, aprotic solvents, and solvent free conditions [19] using either classical heating, microwave [20, 21], ultrasound [22, 23], and visible light (100？W Lamp, THF) irradiations [24]. Also several improved procedures have been reported recently using not only acidic media such as Lewis acids, protic acids, and ionic liquids as promoters [25, 26] but also nonacidic substances such as baker’s yeast [27], graphite [28], and iodine [29, 30]. Heterogeneous solid acids are used also; however, these are advantageous over conventional homogeneous acid catalysts as they can be easily recovered from the reaction mixture by simple
References
[1]
E. W. Hurst and R. Hull, “Two new synthetic substances active against viruses of the psittacosis-lymphogranuloma- trachoma group,” Journal of Medicinal Chemistry, vol. 3, no. 2, pp. 215–229, 1961.
[2]
M. Ashok, B. S. Holla, and N. S. Kumari, “Convenient one pot synthesis of some novel derivatives of thiazolo[2,3-b]dihydropyrimidinone possessing 4-methylthiophenyl moiety and evaluation of their antibacterial and antifungal activities,” European Journal of Medicinal Chemistry, vol. 42, no. 3, pp. 380–385, 2007.
[3]
S. S. Bahekar and D. B. Shinde, “Synthesis and anti-inflammatory activity of some [4,6-(4-substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid derivatives,” Bioorganic & Medicinal Chemistry Letters, vol. 14, no. 7, pp. 1733–1736, 2004.
[4]
T. U. Mayer, T. M. Kapoor, S. J. Haggarty, R. W. King, S. L. Schreiber, and T. J. Mitchison, “Smart molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen,” Science, vol. 286, no. 5441, pp. 971–974, 1999.
[5]
C. O. Kappe, “Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog,” Accounts of Chemical Research, vol. 33, no. 12, pp. 879–888, 2000.
[6]
A. D. Patil, N. V. Kumar, W. C. Kokke et al., “Novel alkaloids from the sponge Batzella sp.: inhibitors of HIV gp120-human CD4 binding,” Journal of Organic Chemistry, vol. 60, no. 5, pp. 1182–1188, 1995.
[7]
B. B. Snider, J. Chen, A. D. Patil, and A. J. Freyer, “Synthesis of the tricyclic portions of batzelladines A, B and D. Revision of the stereochemistry of batzelladines A and D,” Tetrahedron Letters, vol. 37, no. 39, pp. 6977–6980, 1996.
[8]
P. Biginelli, “Derivati aldeidureidici degli eteri acetil-ed ossalacetico,” Gazzetta Chimica Italiana, vol. 23, pp. 360–416, 1893.
[9]
P. Wipf and A. Cunningham, “A solid phase protocol of the Biginelli dihydropyrimidine synthesis suitable for combinatorial chemistry,” Tetrahedron Letters, vol. 36, no. 43, pp. 7819–7822, 1995.
[10]
C. O. Kappe, “100 years of the Biginelli dihydropyrimidine synthesis,” Tetrahedron, vol. 49, no. 32, pp. 6937–6963, 1993.
[11]
D. Dallinger, A. Stadler, and C. O. Kappe, “Solid- and solution-phase synthesis of bioactive dihydropyrimidines,” Pure and Applied Chemistry, vol. 76, no. 5, pp. 1017–1024, 2004.
[12]
C. O. Kappe, “4-aryldihydropyrimidines via the Biginelli condensation: aza-analogs of nifedipine-type calcium channel modulators,” Molecules, vol. 3, no. 1, pp. 1–9, 1998.
[13]
C. O. Kappe and A. Stadler, “The Biginelli dihydropyrimidine synthesis,” Organic Reactions, vol. 63, pp. 1–116, 2004.
[14]
C. Simon, T. Constantieux, and J. Rodriguez, “Utilisation of 1,3-dicarbonyl derivatives in multicomponent reactions,” European Journal of Organic Chemistry, no. 24, pp. 4957–4980, 2004.
[15]
C. O. Kappe, “The generation of dihydropyrimidine libraries utilizing Biginelli multicomponent chemistry,” QSAR and Combinatorial Science, vol. 22, no. 6, pp. 630–645, 2003.
[16]
H. E. Zaugg and W. B. Martin, “α-amidoalkylations at carbon,” in Organic Reactions, vol. 14, pp. 88–90, John Wiley & Sons, New York, NY, USA, 1965.
[17]
C. O. Kappe, “The Biginelli reaction,” in Multicomponent Reactions, pp. 95–120, John Wiley & Sons, New York, NY, USA, 2005.
[18]
L. Z. Gong, X. H. Chen, and X. Y. Xu, “Asymmetric organocatalytic biginelli reactions: a new approach to quickly access optically active 3,4-dihydropyrimidin-2-(1H)-ones,” Chemistry—A European Journal, vol. 13, no. 32, pp. 8920–8926, 2007.
[19]
A. Dondoni and A. Massi, “Parallel synthesis of dihydropyrimidinones using Yb(III)-resin and polymer-supported scavengers under solvent-free conditions. A green chemistry approach to the Biginelli reaction,” Tetrahedron Letters, vol. 42, no. 45, pp. 7975–7978, 2001.
[20]
A. Shaabani and A. Bazgir, “Microwave-assisted efficient synthesis of spiro-fused heterocycles under solvent-free conditions,” Tetrahedron Letters, vol. 45, no. 12, pp. 2575–2577, 2004.
[21]
B. J. Ahn, M. S. Gang, K. Chae, Y. Oh, J. Shin, and W. Chalg, “A microwave-assisted synthesis of 3,4-dihydro-pyrimidin-2-(1H)-ones catalyzed by FeCl3-supported Nanopore Silica under solvent-free conditions,” Journal of Industrial and Engineering Chemistry, vol. 14, no. 3, pp. 401–405, 2008.
[22]
X. Zhang, Y. Li, C. Liu, and J. Wang, “An efficient synthesis of 4-substituted pyrazolyl-3,4-dihydropyrimidin-2(1H)-(thio)ones catalyzed by Mg(ClO4)2 under ultrasound irradiation,” Journal of Molecular Catalysis A, vol. 253, no. 1-2, pp. 207–211, 2006.
[23]
J. T. Li, J. F. Han, J. H. Yang, and T. S. Li, “An efficient synthesis of 3,4-dihydropyrimidin-2-ones catalyzed by NH2SO3H under ultrasound irradiation,” Ultrasonics Sonochemistry, vol. 10, no. 3, pp. 119–122, 2003.
[24]
N. Foroughifar, A. Mobinikhaledi, and H. Fathinejad Jirandehi, “Synthesis of some biginelli compounds in solvent medium using a photochemistry method,” Phosphorus, Sulfur and Silicon and the Related Elements, vol. 178, no. 3, pp. 495–500, 2003.
[25]
E. H. Hu, D. R. Sidler, and U. H. Dolling, “Unprecedented catalytic three component one-pot condensation reaction: an efficient synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydropyrimidin- 2(1H)-ones,” Journal of Organic Chemistry, vol. 63, no. 10, pp. 3454–3457, 1998.
[26]
C. V. Reddy, M. Mahesh, P. V. K. Raju, T. R. Babu, and V. V. N. Reddy, “Zirconium(IV) chloride catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Tetrahedron Letters, vol. 43, no. 14, pp. 2657–2659, 2002.
[27]
A. Kumar and R. A. Maurya, “An efficient bakers' yeast catalyzed synthesis of 3,4-dihydropyrimidin-2-(1H)-ones,” Tetrahedron Letters, vol. 48, no. 26, pp. 4569–4571, 2007.
[28]
Y. Q. Zhang, C. Wang, G. S. Li, J. C. Li, H. M. Liu, and Q. H. Wu, “One-pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Catalyzed by Expandable Graphite,” Chinese Journal of Organic Chemistry, vol. 25, pp. 1265–1267, 2005.
[29]
R. V. Yarapathi, S. Kurva, and S. Tammishetti, “Synthesis of 3,4-dihydropyrimidin-2(1H)ones using reusable poly(4-vinylpyridine-co-divinylbenzene)-Cu(II)complex,” Catalysis Communications, vol. 5, no. 9, pp. 511–513, 2004.
[30]
J. Azizian, A. A. Mohammadi, A. R. Karimi, and M. R. Mohammadizadeh, “KAl(SO4)2·12H2O supported on silica gel as a novel heterogeneous system catalyzed biginelli reaction: one-pot synthesis of di-hydropyrimidinones under solvent-free conditions,” Applied Catalysis A, vol. 300, no. 1, pp. 85–88, 2006.
[31]
N. Mizuno and M. Misono, “Heterogeneous catalysis,” Chemical Reviews, vol. 98, no. 1, pp. 199–217, 1998.
[32]
A. A. Bakibaev and V. D. Filimonov, “Synthesis of hydrogenated acridine-1,8-diones & 1,4-dihydropyrimidines by reaction of urea with 1,3-dicarbonyl compounds,” Russian Journal of Organic Chemistry, vol. 27, pp. 854–859, 1991.
[33]
Y. Yu, D. Liu, C. Liu, and G. Luo, “One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using chloroacetic acid as catalyst,” Bioorganic & Medicinal Chemistry Letters, vol. 17, no. 12, pp. 3508–3510, 2007.
[34]
A. S. Paraskar, G. K. Dewkar, and A. Sudalai, “Cu(OTf)2: a reusable catalyst for high-yield synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Tetrahedron Letters, vol. 44, no. 16, pp. 3305–3308, 2003.
[35]
M. Gohain, D. Prajapati, and S. Sandhub, “A novel Cu-catalysed three-component one-pot synthesis of dihydropyrimidin-2(1H)-ones using microwaves under solvent free conditions,” Synlett, p. 235, 2004.
[36]
Y. Ma, C. Qian, L. Wang, and M. Yang, “Lanthanide triflate catalyzed Biginelli reaction. one-pot synthesis of dihydropyrimidinones under solvent-free conditions,” The Journal of Organic Chemistry, vol. 65, no. 12, pp. 3864–3868, 2000.
[37]
V. T. Kamble, D. B. Muley, S. T. Atkore, and S. D. Dakore, “Three component reaction: an efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones and thiones using heterogeneous catalyst,” Chinese Journal of Chemistry, vol. 28, no. 3, pp. 388–392, 2010.
[38]
B. Gangadasu, S. Palaniappan, and V. J. Rao, “One-pot synthesis of dihydropyrimidinones using polyaniline-bismoclite complex. A facile and reusable catalyst for the biginelli reaction,” Synlett, no. 7, pp. 1285–1287, 2004.
[39]
A. K. Mitra and K. Banerjee, “Clay catalysed synthesis of dihydropyrimidinones under solvent-free conditions,” Synlett, no. 10, pp. 1509–1511, 2003.
[40]
J. Mabry and B. Ganem, “Studies on the Biginelli reaction: a mild and selective route to 3,4-dihydropyrimidin-2(1H)-ones via enamine intermediates,” Tetrahedron Letters, vol. 47, no. 1, pp. 55–56, 2006.
[41]
T. Ghorge, R. Tahilramani, and D. V. Mehta, “Condensed heterocycles from 5-ethoxycarbonyl-6-methyltetrahydropyrimidin-2-ones,” Communications, pp. 405–407, 1975.
[42]
N.-Y. Fu, Y.-F. Yuan, Z. Cao, S.-W. Wang, J.-T. Wang, and C. Peppe, “Indium(III) bromide-catalyzed preparation of dihydropyrimidinones: improved protocol conditions for the Biginelli reaction,” Tetrahedron, vol. 58, no. 24, pp. 4801–4807, 2002.
[43]
J. S. Yadav, B. V. S. Reddy, P. Sridhar et al., “Green protocol for the biginelli three-component reaction: Ag 3PW12O40 as a novel, water-tolerant heteropolyacid for the synthesis of 3,4-dihydropyrimidinones,” European Journal of Organic Chemistry, no. 3, pp. 552–557, 2004.
[44]
K. Folkers and T. B. Johnson, “Researches on pyrimidines. CXXXVI. The mechanism of formation of tetrahydropyrimidines by the Biginelli reaction,” Journal of the American Chemical Society, vol. 55, no. 9, pp. 3784–3791, 1933.
[45]
R. D. Carlos, D. Bernardi, and G. Kirsch, “ZrCl4 or ZrOCl2 under neat conditions: optimized green alternatives for the Biginelli reaction,” Tetrahedron Letters, vol. 48, no. 33, pp. 5777–5780, 2007.
[46]
N. Foroughifar, A. Mobinikhaledi, H. F. Jirandehi, and S. Memar, “Microwave-assisted synthesis of some BI- and tricyclic pyrimidine derivatives,” Phosphorus, Sulfur and Silicon and the Related Elements, vol. 178, no. 6, pp. 1269–1276, 2003.
[47]
B. Ahmed, R. A. Khan, Habibullah, and M. Keshari, “An improved synthesis of Biginelli-type compounds via phase-transfer catalysis,” Tetrahedron Letters, vol. 50, no. 24, pp. 2889–2892, 2009.
[48]
E. Ramu, V. Kotra, N. Bansal, R. Varala, and S. R. Adapa, “Green approach for the efficient synthesis of Biginelli compounds promoted by citric acid under solvent-free conditions,” RASāYAN Journal of Chemistry, vol. 1, no. 1, pp. 188–194, 2008.
