About this Journal Submit a Manuscript Table of Contents
ISRN Organic Chemistry
Volume 2012 (2012), Article ID 415645, 6 pages
http://dx.doi.org/10.5402/2012/415645
Research Article

A Green, Expeditious, One-Pot Synthesis of 3, 4-Dihydropyrimidin-2(1H)-ones Using a Mixture of Phosphorus Pentoxide-Methanesulfonic Acid at Ambient Temperature

1School of Chemical Sciences, North Maharashtra University, Jalgaon 425 001, India
2Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education & Research, Shirpur 425 405, India

Received 4 April 2012; Accepted 25 June 2012

Academic Editors: J. Drabowicz, H. A. Jimenez-Vazquez, F. Machetti, F. C. Pigge, and H. Wakamatsu

Copyright © 2012 Amulrao Borse et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

An expeditious, one-pot method for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones using a mixture of phosphorus pentoxide-methanesulfonic acid (Eaton’s reagent) at room temperature under solvent-free conditions is described. The salient features of this method include short reaction time, green aspects, high yields, and simple procedure.

1. Introduction

The widespread interest in 3,4-dihydropyrimidin-2(1H)-ones, Biginelli compounds, has resulted in enormous efforts towards the synthesis of this biologically important moiety. Several methods have been developed for the synthesis of these compounds, but most of these protocols involve expensive reagents, strong acid catalysts, solvents, of prolonged reaction time and even then provide the products in unsatisfactory yields. With the current global awareness of developing environmentally friendly technologies, it is a need to perform a reaction in neat and nonhazardous conditions for providing a green approach towards organic synthesis [1]. Therefore, it was decided to develop an efficient method for the synthesis of Biginelli compounds. In this communication, we report a straightforward and simple procedures for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones using a mixture of phosphorus pentoxide-methanesulfonic acid (Eaton’s reagent).

Eaton’s reagent (1 : 10 phosphorus pentoxide in methanesulfonic acid) is an inexpensive and commercially available substance synthesized by Eaton in 1973 and found to be a good alternative to polyphosphoric acid which enables the drawbacks of many traditional catalysts to be overcome, because it has a much lower viscosity, it is easier to handle, and no complex separation procedures need to be employed [2]. Many processes that employ a mixture of P2O5/MeSO3H are not only more economical, but also they are more environmentally friendly and offer a number of distinct advantages such as safe in industrial scale, no additional solvent required, chlorine-free, rapid reactions, and high-purity products with excellent yields. The distinctive physical and chemical properties of Eaton’s reagent make it a very useful substance in many different reactions with different applications. The mixture of P2O5/MeSO3H is particularly effective for ring closures. McGarry and Detty successfully used this reagent in cycloacylation reactions for producing chromones and flavones [3]; recently, Zewge and coworkers used Eaton’s reagent to promote the cyclization of aniline derivatives to produce 4-quinolones [4]. P2O5/MeSO3H offers a simple means of producing poly(benzimidazoles) from o-phenylenediamines and aromatic carboxylic acids [5]. Kaboudin and Abedi employed this system for synthesis of aryl mesylates [6].

In continuation of our efforts on developing environmentally benign, green methodologies for biologically active organic compounds [79], herein we report a rapid, ambient temperature, and solvent-free method for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones using Eaton’s reagent. 3,4-dihydropyrimidin-2(1H)-ones, Biginelli compounds, have been synthesized by condensing aldehyde, ethylacetoacetate and urea or thiourea under acidic conditions [10]. Methanesulfonic acid [11] and phosphorus pentoxide [12] have been used as catalysts in the past decade. Both of these transformations require conventional heating and use of organic solvents. In case of methanesulfonic acid, the reaction mixture is refluxed for 6-7 h using ethanol as solvent, and in phosphorus pentoxide, it is refluxed for 3-4 h. In view of these results, it was decided to use Eaton’s reagent (P2O5 and CH3SO3H) under solvent-free conditions at room temperature for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. (Scheme 1).

415645.sch.001
Scheme 1: One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using Eaton’s reagent.

The synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-one derivatives is the area of interest because a large number of biologically active molecules contain this moiety. Many dihydropyrimidinones and their derivatives are pharmacologically important as they possess antitumor, antibacterial, and antiviral properties; they have also emerged as integral backbones of several calcium-channel blockers, vasorelaxants, antihypertensive, and antimitotic agents [1317]. The literature survey reveals that numerous methods have been developed for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones by three-component cyclocondensation of aldehyde, urea, and ethylacetoacetate, which comprises the use of ionic liquids [18], microwave irradiation [19], ultrasound irradiation [20], BF3·OEt2 [21], NiCl2·6H2O and FeCl3·6H2O [22], CoCl2·6H2O [23], BiCl3 [24], InCl3 [25], and InBr3 [26]. Zn(OTf)2 [27], Cu(OTf)2 [28], Bi(OTf)3 [29], p-TSA [30], silica sulphuric acid [31], potassium hydrogen sulphate [32], formic acid [33], chloroacetic acid [34], chlorosulfonic acid [35], P2O5/SiO2 [36], TFA [37], CF3COONH4 [38], p-TSA in biphasic media [39], ZnCl2 [40], and I2 [41].

2. Result and Discussion

In our recent study about the synthesis of Bis(indolyl)methanes under mild conditions, we found that reagent works extremely well for the coupling reaction. In this paper, herein we employed the reagent in a multicomponent, one-pot reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones at room temperature. Eaton’s reagent is a colorless, odorless liquid mixture of nonoxidizing methanesulfonic acid and a powerful dehydrating agent phosphorus pentoxide. The addition of phosphorus pentoxide increases the solubility of organic compounds in methanesulfonic acid; this was introduced by Eaton and has been used enormously in organic synthesis.

In order to standardize the reaction conditions for the condensation reaction, it was decided to synthesize 3,4-dihydropyrimidin-2(1H)-one (4a) from benzaldehyde (1a), urea, and ethylacetoacetate using a mixture of P2O5/MeSO3H, and we found that the reaction is fast when compared to other reported methods. The results are compared with the reported methods, and it is clear from Table 1 that the present method is more efficient.

tab1
Table 1: Comparison of reaction conditions and yield of product (4a) with reported methods versus the present method.

To optimize the reaction condition, the condensation reaction was performed under different conditions (Table 2). In the presence of Eaton’s reagent (2 mmol for each operation), initially 4-chlorobenzaldehyde (1k) was used as model for the reaction with ethylacetoacetate and urea. The reaction carried out at room temperature using ethanol as solvent required 2.3 h for completion, and the product (4k) was obtained in 60% yield (Entry 1). When the reaction was performed by using ethanol under refluxing conditions, it required 2 h and provided the product in 65% yield (Entry 2). When the reaction was performed without any solvent at room temperature using 2 mmol of Eaton’s reagent, the reaction was completed in 5 min, and the product (4k) was obtained in 85% yield (Entry 3).

tab2
Table 2: Optimization of reaction conditions for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones (4k) with 4-chlorobenzaldehyde.

To explore the scope and limitations of this reaction, we extended the procedure to various aromatic aldehydes carrying either electron-releasing or electron-withdrawing substituents in the ortho-, meta-, and para-positions. We have also synthesized the compounds with thiourea and methylacetoacetate, and we found that the reaction proceeds very efficiently with all the cases, and the products are obtained in high yields (Table 3).

tab3
Table 3: Expeditious synthesis of 3,4-dihydropyrimidin-2(1H)-ones (4a–4u) using Eaton’s reagent under solvent-free conditionsa.

3. Experimental

Eaton’s reagent (7.7/92.3% by weight of P2O5/MeSO3H) was purchased from Sigma-Aldrich. All melting points were recorded in open capillaries. The purity of the compounds was checked by TLC on silica gel G (Merck). 1H NMR spectra were recorded on Varian 300 MHz instrument, in DMSO - 𝑑 6 using TMS as the internal standard. IR spectra were obtained using a Nujol for solids on a Perkin-Elmer-1710 spectrophotometer. Mass spectra were recorded on Thermo Finnigan (Model-LCQ Advantage MAX) mass spectrometer.

3.1. General Method for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones (4a–4u)

A mixture of aromatic aldehyde 1 (1 mmol), ethylacetoacetate 2 (1 mmol), and urea 3 (1.5 mmol) was stirred with Eaton’s reagent (2 mmol) at room temperature for appropriate time (mentioned in Table 3). After completion of the reaction (monitored by TLC), the reaction mass was transferred to an excess saturated sodium carbonate solution. The solid products separated out, were filtered, and washed with sufficient water and dried. The crude products on recrystallization from ethanol provided 3,4-dihydropyrimidin-2(1H)-ones (4a–4u) in 75–96% yield.

3.2. Spectral Data for the Selected Compounds
3.2.1. 5-Ethoxycarbonyl-4-(phenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4a)

Mp 202–204°C; IR(nujol) cm−1: 3244 (NH), 3108 (NH), 1729 (C=O), 1645 (C=C), 1460 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 9.18 (br s, 1H, NH), 7.73 (br s, 1H, NH), 7.21–7.34 (m, 5H, ArH), 5.13 (d, 1H, 𝐽 = 3.3 Hz, CH), 3.97 (q, 2H, 𝐽 = 7.15 Hz, OCH2), 2.24 (s, 3H, CH3), 1.08 (t, 3H, 𝐽 = 7.15 Hz, CH3); MS ( 𝑚 / 𝑧 ) : 260 (M+).

3.2.2. 5-Ethoxycarbonyl-4-(2,3-dichlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4d)

Mp 248–250°C; IR(nujol) cm−1: 3357 (NH), 3108 (NH), 1696 (C=O), 1646 (C=C), 1459 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 9.32 (br s, 1H, NH), 7.78 (br s, 1H, NH), 7.27–7.56 (m, 3H, ArH), 5.67 (d, 1H, 𝐽 = 2.4 Hz, CH), 3.88 (q, 2H, 𝐽 = 6.9 Hz, OCH2), 2.29 (s, 3H, CH3), 0.96 (t, 3H, 𝐽 = 7.15 Hz, CH3); MS ( 𝑚 / 𝑧 ) : 329 (M+).

3.2.3. 5-Ethoxycarbonyl-4-(2,4-dichlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4 g)

Mp 252–254°C; IR(nujol) cm−1: 3359 (NH), 3108 (NH), 1716 (C=O), 1640 (C=C), 1459 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 9.31 (br s, 1H, NH), 7.76 (br s, 1H, NH), 7.29–7.56 (m, 3H, ArH), 5.58 (s, 1H,CH), 3.88 (q, 2H, 𝐽 = 7.15Hz, OCH2), 2.28 (s, 3H, CH3), 0.99 (t, 3H, 𝐽 = 6.9Hz, CH3); MS ( 𝑚 / 𝑧 ) : 329 (M+).

3.2.4. 5-Ethoxycarbonyl-4-(4-bromophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4 h)

Mp 216–218°C; IR(nujol) cm−1: 3345 (NH), 3110 (NH), 1704 (C=O), 1645 (C=C), 1462 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 9.20 (br s, 1H, NH), 7.73 (br s, 1H, NH), 7.48 (d, 2H, 𝐽 = 8.1 Hz, ArH), 7.14 (d, 2H, 𝐽 = 8.1 Hz, ArH), 5.07 (d, 1H, 𝐽 = 2.8 Hz, CH), 3.93 (q, 2H, 𝐽 = 6.9 Hz, OCH2), 2.20 (s, 3H, CH3), 1.04 (t, 3H, 𝐽 = 7.15 Hz, CH3); MS ( 𝑚 / 𝑧 ) : 339 (M+).

3.2.5. 5-Ethoxycarbonyl-4-(4-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4i)

Mp 226–228°C; IR(nujol) cm−1: 3507 (NH), 3108 (NH), 1682 (C=O), 1645 (C=C), 1460 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 9.06 (br s, 1H, NH), 7.57 (br s, 1H, NH), 7.02 (d, 2H, ArH), 6.67 (d, 2H, ArH), 5.03 (d, 1H, 𝐽 = 2.9 Hz, CH), 3.97 (q, 2H, 𝐽 = 7.15 Hz, OCH2), 2.22 (s, 3H, CH3), 1.09 (t, 3H, 𝐽 = 7.15 Hz, CH3); MS ( 𝑚 / 𝑧 ) : 277 (M++H).

3.2.6. 5-Mthoxycarbonyl-4-(4-fluorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4n)

Mp 208–210°C; IR(nujol) cm−1: 3326(NH), 3204 (NH), 1695 (C=O), 1666 (C=C), 1460 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 9.24 (br s, 1H, NH), 7.76 (br s, 1H, NH), 7.11–7.27 (m, 4H, ArH), 5.13 (d, 1H, 𝐽 = 2.9 Hz, CH), 3.51 (s, 3H, CH3O), 2.24 (s, 3H, CH3); MS ( 𝑚 / 𝑧 ) : 265 (M++H).

3.2.7. 5-Methoxycarbonyl-4-(phenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4o)

Mp 212–214°C; IR(nujol) cm−1: 3334 (NH), 3108 (NH), 1704 (C=O), 1650 (C=C), 1459 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 9.21 (br s, 1H, NH), 7.75 (br s, 1H, NH), 7.21–7.31 (m, 5H, ArH), 5.13 (s, 1H,CH), 3.51 (s, 3H, CH3O), 2.23 (s, 3H, CH3); MS ( 𝑚 / 𝑧 ) : 247 (M++H).

3.2.8. 5-Ethoxycarbonyl-4-(4-methylyphenyl)-6-methyl-3,4-dihydro-pyrimidin-2(1H)-thione (4s)

Mp 194–198°C; IR(nujol) cm−1: 3323 (NH), 3165 (NH), 1670 (C=O), 1575 (C=C), 1459 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 10.28 (br s, 1H, NH), 9.60 (br s, 1H, NH), 7.12 (d, 2H, 𝐽 = 8.1 Hz, ArH), 7.06 (d, 2H, 𝐽 = 8.1 Hz, ArH), 5.10 (d, 1H, 𝐽 = 2.8 Hz, CH), 3.97 (q, 2H, 𝐽 = 6.95 Hz, OCH2), 2.25 (s, 3H, CH3), 2.24 (s, 3H, ArCH3), 1.08 (t, 3H, 𝐽 = 7.15 Hz, CH3); MS ( 𝑚 / 𝑧 ) : 291 (M++H).

3.2.9. 5-Ethoxycarbonyl-4-(4-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (4t)

Mp 196–198°C; IR(nujol) cm−1: 3357 (NH), 3108 (NH), 1670 (C=O), 1644 (C=C), 1459 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 10.24(br s, 1H, OH) 9.55 (br s, 1H, NH), 9.43 (br s, 1H, NH), 6.99 (d, 2H, 𝐽 = 8.1 Hz, ArH), 6.69 (d, 2H, 𝐽 = 8.1 Hz, ArH), 5.04 (d, 1H, 𝐽 = 2.8 Hz, CH), 3.98 (q, 2H, 𝐽 = 6.9 Hz, OCH2), 2.26(s, 3H, CH3), 1.09 (t, 3H, 𝐽 = 6.9 Hz, CH3); MS ( 𝑚 / 𝑧 ) : 293 (M++H).

3.2.10. 5-Ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydro-pyrimidin-2(1H)-thione (4u)

Mp 140–142°C; IR(nujol) cm−1: 3311 (NH), 3165 (NH), 1664 (C=O), 1574 (C=C), 1459 (CH); 1H NMR (300 MHz, DMSO - 𝑑 6 ): 𝛿 H 10.28 (br s, 1H, NH), 9.59 (br s, 1H, NH), 7.12 (d, 2H, 𝐽 = 8.6 Hz, ArH), 6.89 (d, 2H, 𝐽 = 8.6 Hz, ArH), 5.10 (d, 1H, 𝐽 = 3.9 Hz, CH), 3.99 (q, 2H, 𝐽 = 7.15 Hz, OCH2), 3.71 (s, 3H, CH3O), 2.27 (s, 3H, CH3), 1.10 (t, 3H, 𝐽 = 7.15 Hz, CH3); MS ( 𝑚 / 𝑧 ) : 307 (M++H).

4. Conclusion

In summary, we have developed an efficient, ecofriendly and solvent-free method for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones (4a–4u). The present method which makes use of commercially available Eaton’s reagent offers a very attractive features such as shorter reaction times, simple operations with extremely milder conditions, green aspects avoiding hazardous organic solvents, toxic catalyst, and provides good to excellent yields.

Acknowledgments

M. N. Patil is thankful to UGC, New Delhi for SAP fellowship under the scheme “Research Fellowship in Sciences for Meritorious Students.” Authors are also thankful to Professor Raghao S. Mali and Dr. Sidhanath V. Bhosale for their constant encouragement.

References

  1. U. R. Kalkote, V. T. Sathe, R. K. Kharul, S. P. Chavan, and T. Ravindranathan, “Quinolone antibiotics: study of reactivity and impurity profile of piperazine with chloro-fluoro-quinolone carboxylic acid in aqueous medium,” Tetrahedron Letters, vol. 37, no. 37, pp. 6785–6786, 1996. View at Publisher · View at Google Scholar · View at Scopus
  2. P. E. Eaton, G. R. Carlson, and J. T. Lee, “Phosphorus pentoxide-methanesulfonic acid. A convenient alternative to polyphosphoric acid,” Journal of Organic Chemistry, vol. 38, no. 23, pp. 4071–4073, 1973. View at Scopus
  3. L. W. McGarry and M. R. Detty, “Synthesis of highly functionalized flavones and chromones using cycloacylation reactions and C-3 functionalization. A total synthesis of hormothamnione,” Journal of Organic Chemistry, vol. 55, no. 14, pp. 4349–4356, 1990. View at Scopus
  4. D. Zewge, C. Y. Chen, C. Deer, P. G. Dormer, and D. L. Hughes, “A mild and efficient synthesis of 4-quinolones and quinolone heterocycles,” Journal of Organic Chemistry, vol. 72, no. 11, pp. 4276–4279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. A. I. Fomenkov, I. V. Blagodatskikh, I. I. Ponomarev, Y. A. Volkova, I. I. Ponomarev, and A. R. Khokhlov, “Synthesis and molecular-mass characteristics of some cardo poly(benzimidazoles),” Polymer Science—Series B, vol. 51, no. 5-6, pp. 166–173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. B. Kaboudin and Y. Abedi, “A novel synthesis of aryl mesylates via one-pot demethylation-mesylation of aryl methyl ethers using a mixture of phosphorus pentoxide in methanesulfonic acid,” Synthesis, no. 12, pp. 2025–2028, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. A. U. Borse, M. N. Patil, and N. L. Patil, “Expeditious, mild and solvent free synthesis of Bis(indolyl)methanes, Using a mixture of phosphorus pentoxide in methanesulfonic acid,” E-Journal of Chemistry, vol. 9, no. 3, pp. 1313–1319, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. V. S. Patil, K. P. Nandre, A. U. Borse, and S. V. Bhosale, “InCl3-catalysed [2+3] cycloaddition reaction: a rapid synthesis of 5-substituted 1H-tetrazoles under microwave irradiation,” E-Journal of Chemistry, vol. 9, no. 3, pp. 1145–1152, 2012. View at Publisher · View at Google Scholar
  9. K. P. Nandre, J. K. Salunke, J. P. Nandre, V. S. Patil, A. U. Borse, and S. V. Bhosale, “Glycerol mediated synthesis of 5-substituted 1H-tetrazoles under catalyst free conditions,” Chinese Chemical Letters, vol. 23, pp. 161–164, 2012. View at Publisher · View at Google Scholar
  10. P. Biginelli, “The first synthesis of dihydropyrimidinone by refluxing a mixture of an aldehyde, a β-ketoester, and urea under strongly acidic condition,” Gazzetta Chimica Italiana, vol. 23, pp. 360–413, 1893.
  11. T. S. Jin, H. X. Wang, C. Y. Xing, X. L. Li, and T. S. Li, “An efficient one-pot synthesis of 3,4-dihydropyrimidin-2-ones catalyzed by methanesulfonic acid,” Synthetic Communications, vol. 34, no. 16, pp. 3009–3016, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. M. B. Deshmukh, P. V. Anbhule, S. D. Jadhav, A. R. Mali, S. S. Jagtap, and S. A. Deshmukh, “An efficient, simple, one pot synthesis of dihydropyrimidine-2(1H)ones using phosphorus pentoxide,” Indian Journal of Chemistry—Section B, vol. 46, no. 9, pp. 1545–1548, 2007. View at Scopus
  13. S. J. Haggarty, T. U. Mayer, D. T. Miyamoto et al., “Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis,” Chemistry and Biology, vol. 7, no. 4, pp. 275–286, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Yarim, S. Saraç, F. S. Kiliç, and K. Erol, “Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/ 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives,” Farmaco, vol. 58, no. 1, pp. 17–24, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. 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. View at Publisher · View at Google Scholar · View at Scopus
  16. K. S. Atwal, G. C. Rovnyak, S. D. Kimball et al., “Dihydropyrimidine calcium channel blockers. 2. 3-Substituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines,” The Journal of Medicinal Chemistry, vol. 33, no. 9, pp. 2629–2635, 1990. View at Publisher · View at Google Scholar · View at Scopus
  17. B. Jauk, T. Pernat, and C. O. Kappe, “Design and synthesis of a conformationally rigid mimic of the dihydropyrimidine calcium channel modulator SQ 32,926,” Molecules, vol. 5, no. 3, pp. 227–239, 2000. View at Scopus
  18. J. Peng and Y. Deng, “Ionic liquids catalyzed Biginelli reaction under solvent-free conditions,” Tetrahedron Letters, vol. 42, no. 34, pp. 5917–5919, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. B. K. Banik, A. T. Reddy, A. Datta, and C. Mukhopadhyay, “Microwave-induced bismuth nitrate-catalyzed synthesis of dihydropyrimidones via Biginelli condensation under solventless conditions,” Tetrahedron Letters, vol. 48, no. 41, pp. 7392–7394, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. 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. View at Publisher · View at Google Scholar · View at Scopus
  21. 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. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Lu and Y. Bai, “Catalysis of the Biginelli reaction by ferric and nickel chloride hexahydrates. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Synthesis, no. 4, pp. 466–470, 2002. View at Scopus
  23. J. Lu, Y. J. Bai, Y. H. Guo, Z. J. Wang, and H. R. Ma, “CoCl2· 6H2O or LaCl3· 7H2O catalyzed biginelli reaction. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Chinese Journal of Chemistry, vol. 20, no. 7, pp. 681–687, 2002. View at Scopus
  24. K. Ramalinga, P. Vijayalakshmi, and T. N. B. Kaimal, “Bismuth(III)-catalyzed synthesis of dihydropyrimidinones: improved protocol conditions for the Biginelli reaction,” Synlett, no. 6, pp. 863–865, 2001. View at Scopus
  25. B. C. Ranu, A. Hajra, and U. Jana, “Indium(III) chloride-catalyzed one-pot synthesis of dihydropyrimidinones by a three-component coupling of 1,3-dicarbonyl compounds, aldehydes, and urea: an improved procedure for the Biginelli reaction,” Journal of Organic Chemistry, vol. 65, no. 19, pp. 6270–6272, 2000. View at Publisher · View at Google Scholar · View at Scopus
  26. 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. View at Publisher · View at Google Scholar · View at Scopus
  27. H. Xu and Y. G. Wang, “A rapid and efficient Biginelli reaction catalyzed by zinc triflate,” Chinese Journal of Chemistry, vol. 21, no. 3, pp. 327–331, 2003. View at Scopus
  28. 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. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Varala, M. M. Alam, and S. R. Adapa, “Bismuth triflate catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2 (1H)-ones: an improved protocol for the Biginelli reaction,” Synlett, no. 1, pp. 67–70, 2003. View at Scopus
  30. T. Jin, S. Zhang, and T. Li, “p-toluenesulfonic acid-catalyzed efficient synthesis of dihydropyrimidines: improved high yielding protocol for the Biginelli reaction,” Synthetic Communications, vol. 32, no. 12, pp. 1847–1851, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. P. Salehi, M. Dabiri, M. A. Zolfigol, and M. A. Bodaghi Fard, “Silica sulfuric acid: an efficient and reusable catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Tetrahedron Letters, vol. 44, no. 14, pp. 2889–2891, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Tu, F. Fang, S. Zhu, T. Li, X. Zhang, and Q. Zhuang, “A new Biginelli reaction procedure using potassium hydrogen sulfate as the promoter for an efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one,” Synlett, vol. 3, pp. 537–539, 2004. View at Scopus
  33. C. Jiang and Q. D. You, “An efficient and solvent-free one-pot synthesis of dihydropyrimidinones under microwave irradiation,” Chinese Chemical Letters, vol. 18, no. 6, pp. 647–650, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. 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 and Medicinal Chemistry Letters, vol. 17, no. 12, pp. 3508–3510, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. S. A. Kotharkar, R. R. Nagawade, and D. B. Shinde, “Chlorosulfonic acid catalyzed highly efficient solvent-free synthesis of 3, 4-Dihydropyrimidin-2(1H)-one and thiones,” Ukrainica Bioorganica Acta, vol. 2, pp. 17–21, 2006.
  36. A. Hasaninejad, A. Zare, F. Jafari, and A. R. Moosavi-Zare, “P2O5/SiO2 as an efficient, green and heterogeneous catalytic system for the solvent-free synthesis of 3,4-dihydropyrimidin-2-(1H)-ones (and -thiones),” E-Journal of Chemistry, vol. 6, no. 2, pp. 459–465, 2009. View at Scopus
  37. D. Shobha, M. A. Chari, and K. H. Ahn, “An efficient Biginelli one-pot synthesis of new benzoxazole-substituted dihydropyrimidinones and thiones catalysed by trifluoro acetic acid under solvent-free conditions,” Chinese Chemical Letters, vol. 20, no. 9, pp. 1059–1061, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. C. Raju, R. Uma, K. Madhaiyan, R. Sridhar, and S. Ramakrishna, “Ammonium Trifluoroacetate-Mediated Synthesis of 3, 4-dihydropyrimidin-2(1H)-ones,” ISRN Organic Chemistry, vol. 2011, Article ID 273136, 5 pages, 2011. View at Publisher · View at Google Scholar
  39. A. K. Bose, M. S. Manhas, S. Pednekar et al., “Large scale Biginelli reaction via water-based biphasic media: a green chemistry strategy,” Tetrahedron Letters, vol. 46, no. 11, pp. 1901–1903, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. Q. Sun, Y. Q. Wang, Z. M. Ge, T. M. Cheng, and R. T. Li, “A highly efficient solvent-free synthesis of dihydropyrimidinones catalyzed by zinc chloride,” Synthesis, vol. 7, pp. 1047–1051, 2004. View at Scopus
  41. D. Kataki, P. Chakraborty, P. Sarmah, and P. Phukan, “Scalable synthesis of 3,4-dihydropyrimidin-2(1H)-ones under solvent free condition,” Indian Journal of Chemical Technology, vol. 13, no. 5, pp. 519–521, 2006. View at Scopus
  42. H. Sharghi and M. Jokar, “Al2O3/MeSO3H: a novel and recyclable catalyst for one-pot synthesis of 3,4-dihydropyrimidinones or their sulfur derivatives in Biginelli condensation,” Synthetic Communications, vol. 39, no. 6, pp. 958–979, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. D. Russowsky, F. A. Lopes, V. S. S. Da Silva, K. F. S. Canto, M. G. Montes D'Oca, and M. N. Godoi, “Multicomponent Biginelli's synthesis of 3,4-dihydropyrimidin-2(1H)-ones promoted by SnCl2·2H2O,” Journal of the Brazilian Chemical Society, vol. 15, no. 2, pp. 165–169, 2004. View at Scopus
  44. Y. Cao, Y. Guo, and Y. Li, “Biginelli reaction catalyzed by PEG400-KH2PO4 under solvent-free conditions,” Chemical Journal on Internet, vol. 9, no. 6, 2007. View at Scopus
  45. A. Debache, M. Amimour, A. Belfaitah, S. Rhouati, and B. Carboni, “A one-pot Biginelli synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones catalyzed by triphenylphosphine as Lewis base,” Tetrahedron Letters, vol. 49, no. 42, pp. 6119–6121, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. A. Shaabani and A. Rahmati, “Ionic liquid promoted efficient synthesis of 3,4-dihydropyrimidin-2-(1H)- ones,” Catalysis Letters, vol. 100, no. 3-4, pp. 177–179, 2005. View at Publisher · View at Google Scholar · View at Scopus