A simple protocol for the efficient preparation of aryl and heteroaryl substituted dihydropyrimidinone has been achieved via initial Knoevenagel, subsequent addition, and final cyclization of aldehyde, ethylcyanoacetate, and guanidine nitrate in the presence of piperidine as a catalyst in solvent-free under microwave irradiation. The synthesized compounds showed a good anti-inflammatory, antibacterial, and antifungal activity. 1. Introduction Pyrimidinones have been paid increasing attention, due to their various therapeutic and pharmacological properties, such as antiviral, antibacterial, antihypertensive, and antitumor effects [1]. More recently, they emerged as integral backbones of several calcium blockers, antihypertensive agents, α-1a-antagonists, and neuropeptide Y (NPY) antagonists [2]. Pyrimidinone derivatives are found as core units in many marine alkaloids (batzelladine and carambine), which have been found to be potent to HIV-gp-120 CD4 inhibitors [3]. Due to the remarkable biological utilization, the pyrimidinones attract many researchers as well as academicians. Recently, several methods improved the procedure using phosphorus pentoxide-methanesulfonic acid [4], potassium ter-butoxide (t-BuOK) [5], ammonium dihydrogen phosphate [6], silica-gel [7], mesoporous molecular sieve MCM-41 [8], cyanuric chloride [9], nano-BF3·SiO2 [10], silica gel-supported polyphosphoric Acid [11], zirconium(IV) chloride [12], and indium(III) bromide [13] as catalysts. However, some of these one-pot procedures generally require strong protic or Lewis acids, prolonged reaction times, and high temperature. Consequently, there is a scope for further modification towards mild reaction condition, increased variation of the substituents, and improved yields. Microwave promoted solvent-free reactions [14] are well known as environmentally benign methods that also usually provide improved selectivity, enhanced reaction rates, cleaner products, and manipulative simplicity [15]. However, these procedures are practically limited as the solvents in microwave oven at elevated temperatures create high pressures, which may cause explosion. To circumvent these problems, there is a need for the development of newer methods which proceed under mild and solvent free condition. Nowadays solvent-free reactions gained much importance in organic synthesis because of the high yields and shorter reaction times. Earlier reported procedures for the synthesis of pyrimidine derivatives typically involved longer reaction time and fewer yields [16]. In the present communication, we would like
References
[1]
C. O. Kappe, “100 years of the Biginelli dihydropyrimidine synthesis,” Tetrahedron, vol. 49, no. 32, pp. 6937–6963, 1993.
[2]
G. C. Rovnyak, S. D. Kimball, B. Beyer et al., “Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators,” Journal of Medicinal Chemistry, vol. 38, no. 1, pp. 119–129, 1995.
[3]
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.
[4]
A. Borse, P. Mahesh, P. Nilesh, and S. Rohan, “A green, expeditious, one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones using a mixture of phosphorus pentoxide-methanesulfonic acid at ambient temperature,” ISRN Organic Chemistry, vol. 2012, Article ID 415645, 6 pages, 2012.
[5]
D. Abdelmadjid, C. Louisa, B. Raouf, and C. Bertrand, “A one-pot multi-component synthesis of dihydropyrimidinone/thione and dihydropyridine derivatives via Biginelli and Hantzsch condensations using t-BuOK as a catalyst under solvent-free conditions,” The Open Organic Chemistry Journal, vol. 6, pp. 12–20, 2012.
[6]
T. Reza, M. Behrooz, and G. Malihe, “Ammonium dihydrogen phosphate catalyst for one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones,” Chinese Journal of Catalysis, vol. 33, no. 4–6, pp. 659–665, 2012.
[7]
S. Agarwal, U. Aware, A. Patil, et al., “Silica-gel catalyzed facile synthesis of 3, 4-dihydropyrimidinones,” Bulletin of Korean Chemical Society, vol. 33, no. 2, pp. 377–378, 2012.
[8]
R. Hekmatshoar, M. Heidari, M. M. Heravi, and B. Baghernejad, “Mesoporous molecular sieve MCM-41 catalyzed one-pot synthesis of 3,4-dihydro-2(1H)-pyrimidinones and -thiones under solvent-free conditions,” Bulletin of the Chemical Society of Ethiopia, vol. 25, no. 2, pp. 309–313, 2011.
[9]
J. A. Kumar, C. Shanmugam, and P. H. Babu, “One pot synthesis of dihydropyrimidinones catalyzed by Cyanuric chloride: an improved procedure for the Biginelli reaction,” Der Pharma Chemica, vol. 3, no. 4, pp. 292–297, 2011.
[10]
B. F. Mirjalili, A. Bamoniri, and A. Akbari, “One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones (thiones) promoted by nano-BF3？·？SiO2,” Journal of the Iranian Chemical Society, vol. 8, supplement 1, pp. S135–S140, 2011.
[11]
M. Zeinali-Dastmalbaf, A. Davoodnia, M. M. Heravi, N. Tavakoli-Hoseini, A. Khojastehnezhad, and H. A. Zamani, “Silica gel-supported polyphosphoric acid (PPA-SiO2) catalyzed one-pot multi-component synthesis of 3, 4-dihydropyrimidin-2(1H)-ones and -thiones: an efficient method for the Biginelli reaction,” Bulletin of the Korean Chemical Society, vol. 32, no. 2, pp. 656–658, 2011.
[12]
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.
[13]
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.
[14]
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.
[15]
M. M. Abelman, S. C. Smith, and D. R. James, “Cyclic ketones and substituted α-keto acids as alternative substrates for novel Biginelli-like scaffold syntheses,” Tetrahedron Letters, vol. 44, no. 24, pp. 4559–4562, 2003.
[16]
M. Kidwai, K. Singhal, and S. Kukreja, “One-pot green synthesis for pyrimido[4,5-d]pyrimidine derivatives,” Zeitschrift fur Naturforschung B, vol. 62, no. 5, pp. 732–736, 2007.
[17]
M. Kidwai, “Dry media reactions,” Pure and Applied Chemistry, vol. 73, no. 1, pp. 147–151, 2001.
[18]
M. B. Patil, S. S. Jalalpure, H. J. Pramod, and F. V. Manvi, “Antiinflammatory activity of the leaves of Anacardium occidentale linn,” Indian Journal of Pharmaceutical Sciences, vol. 65, no. 1, pp. 70–72, 2003.
[19]
N. K. Jain, M. K. Chourasia, S. Jain, S. K. Jain, and N. K. Jain, “Development and characterization of engineered commensal bacteria for the delivery of enzymes,” Indian Journal of Pharmaceutical Sciences, vol. 65, no. 2, pp. 113–121, 2003.
[20]
A. R. Saundane, K. Rudresh, N. D. Satyanarayan, and S. P. Hiremath, “Pharmacological screening of 6H, 11H-indolo [3, 2-c] isoquinolin-5-ones and their derivatives,” Indian Journal of Pharmaceutical Sciences, vol. 60, no. 6, pp. 379–383, 1998.
[21]
T. Kadre, S. R. Jetti, A. Bhatewara, P. Paliwal, and S. Jain, “Green protocol for the synthesis of 3, 4-dihydropyrimidin-2(1H)-ones/thiones using TBAB as a catalyst and solvent free condition under microwave irradiation,” Archives of Applied Science Research, vol. 4, no. 2, pp. 988–993, 2012.
