Biological Activity and Efficient Synthesis of 3, 4-Dihydropyrimidin-2-(1H)-one/thione Derivatives

Author

Department of Chemistry, Faculty of Science, Islamic Azad University, Tonekabon Branch, Tonekabon, Iran

Abstract

The present study aimed to use a method for the synthesis of some 3, 4-dihydropyrimidin-2-(1H) - ones/thiones. The study tried to answer the question whether this reaction can be performed without solvent and with new catalyst or not. To find answer to the question, we described a novel protocol for the efficient synthesis of 3, 4-dihydropyrimidin-2-(1H)-one derivatives using aromatic aldehyde, ethylacetoacetate, and urea/thiourea under solvent-free conditions by using SiO2-CaCl2as acatalyst. Using this catalyst has some advantages; it's high yields, usable in mild conditions, available, reusable, ecofriendly, cost effective and environmentally friendly. The structural features of the synthesized compounds were characterized by IR, 1H NMR and 13C NMR. The compounds were screened for antimicrobial activity. The results showed these compounds react against all the tested bacteria. We have demonstrated a novel method for the synthesis of substituted dihydropyrimidinones catalyzed by SiO2-CaCl2 under solvent-free conditions.

Keywords


  1. Kappe C.O., 1993. 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron. 49(32), 6937ââ‚‌“6963.
  2. Ma, N., Jiang B., Zhang G., Tu S.J., Wever W., Li G., 2010. New multicomponent domino reactions (MDRs) in water: highly chemo-, regio- and stereoselective synthesis of spiro{[1,3]dioxanopyridine}-4,6-diones and pyrazolo[3,4-b]pyridines. Green Chem. 12(8), 1357ââ‚‌“1361.
  3. Kappe C.O., 2000. Recent advances in the Biginelli dihydropyrimidine synthesis: new tricks from an old dog. Accounts Chem Res. 33(12), 879ââ‚‌“888.
  4. Trofimov B.A., Andriyankova L.V., Belyaeva K.V., Mal'kina A.G., Nikitina L.P., Afonin A.V., Ushakov I.A., 2010. C2-functionalization of 1-substituted imidazoles with aldehydes and electron-deficient acetylenes: a novel three-component reaction. European J Org Chem. 9. 1772ââ‚‌“1777.
  5. Chen W.B., Wu Z. J., Pei Q.L., Cun L.F., Zhang X.M., Yuan W.C., 2010. Highly enantioselective construction of spiro[4H-pyran-3,3ââ‚‌²-oxindoles] through a domino knoevenagel/Michael/Cyclization sequence catalyzed by cupreine. Organic Lett. 12(14), 3132ââ‚‌“3135.
  6. Yue T., Wang M.X., Wang D.X., Masson G., Zhu J., 2009. Catalytic asymmetric Passerini-type reaction: chiral aluminum-organophosphate-catalyzed ena-ntioselective α-addition of isocyanides to aldehydes. J Org Chem. 74(21), 8396ââ‚‌“8399.
  7. Adib M., Sheikhi E., Kavoosi A., Bijanzadeh H.R., 2010. Synthesis of 2-(alkylamino)-5-{alkyl[(2-oxo-2H-chromen-3-yl)carbonyl]amino}-3,4-furandicarboxylates using a multi-component reaction in water. Tetrahedron. 66(47), 9263ââ‚‌“9269.
  8. Kolla S.R., Lee Y.R., 2012. Efficient one-pot synthesis of β-phosphono malonates and 2-amino-4H-chromen-4-ylphosphonate derivatives by ethylenediamine diacetate-catalyzed three-component reactions. Tetrahedron. 68(1), 226ââ‚‌“237.
  9. Wang S.L., Wu F.Y., Cheng C., Zhang G., Liu Y.P., Jiang B., Shi F., Tu S.J., 2011. Multicomponent synthesis of poly-substituted benzo[a]pyrano-[2, 3-c] phenazine derivatives under microwave heating. ACS Combinatorial Science. 13(2), 135ââ‚‌“139.
  10. Willy B., Müller T.J.J., 2008. Regioselective three-component synthesis of highly fluorescent 1, 3, 5-trisubstituted pyrazoles. European J Org Chem. 24, 4157ââ‚‌“4168.
  11. Heravi M.M., Baghernejad B., Oskooie H.A., Hekmatshoar R., 2008. A novel and facile synthesis of 2-(cyclohexylamino)-6, 7-dihydro-3-aryl-1H-indole-4(5H)-ones via a one-pot multi-component reaction. Tetrahedron Lett. 49(42), 6101ââ‚‌“6103.
  12. Biginelli P., 1893. Aldehyde-urea derivatives of aceto- and oxaloacetic acids. Gazzetta Chimica Italiana. 23, 360ââ‚‌“413.
  13. Kolvari E., Mirzaeeyan M., 2013. Al(NO3)3ââ‚‌¢9H2O: an efficient catalyst for the one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones both under reflux or solvent-free conditions. Journal of Chemistry. Vol. 2013, Article ID 325268, 5.
  14. Reddy C.V., Mahesh M., Raju P.V.K., Babu T.R., Reddy V.V.N., 2002. Zirconium(IV) chloride catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Tetrahedron Lett. 43(14), 2657ââ‚‌“2659.
  15. Salehi P., Dabiri M., Zolfigol M.A., Bodaghi Fard M.A., 2003. Silica sulfuric acid: an efficient and reusable catalyst for the one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones. Tetrahedron Lett. 44(14), 2889ââ‚‌“2891.
  16. Xu F., Wang J.J., Tian Y.P., 2008. New procedure for one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones by Biginelli reaction. Synth Commun. 38(8), 1299ââ‚‌“1310.
  17. De S.K., Gibbs R.A., 2005. Ruthenium(III) chloride-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones under solvent-free conditions. Synthesis. 11, 1748ââ‚‌“1750.
  18. Abbasi E., Hatamjafari F., 2013. Glutamic acid as an efficient catalyst for synthesis of dihydropyrimidinones. Oriental J Chem. 29(2), 731ââ‚‌“733.
  19. Slimi H., Moussaoui Y., Salem R.B., 2011. Synthesis of 3, 4-dihydropyrimidin-2(1H)-ones/thiones via Biginelli reaction promoted by bismuth(III) nitrate or PPh3 without solvent. Arabian J Chem. DOI:10.1016 / J.Arabjc. 2011. 06. 10.
  20. Shafiee M.R.M., 2011. Heterogeneous catalyst for the environmentally friendly preparation of N,Nââ‚‌²-alkylidene bisamides under solvent-free conditions. Canadian J Chem. 89(5), 555-561.
  21. Uma maheswari Devi P., Srinivasa Reddy P., Usha Rani N.R., Reddanna P., 2000. Lipoxygenase metabolites of a-linolenic acid in the development of resistance in pigeonpea, Cajanus cajan (L.) Millsp., seedlings against Fusarium udum infection. European J Plant Path. 106(9), 857-865.
  22. Colle J.G., Duguid J.P., Firaser A.G., Mannion B.P., 1989. Mackie & Mecartney Practical Medicinal Microbiology. 13th edn; Churchil : Edinburgh and London. 2, 553-558.