All Title Author
Keywords Abstract


Synthesis of Some Hexahydroquinazolinones Using K3AlF6(Al2O3/KF) as an Efficient Catalyst in Some Hexahydroquinazolinone Derivatives

DOI: 10.4236/ijoc.2017.73018, PP. 240-253

Keywords: 4-Aryl-1,3,4,6,7,8-Hexahydroquinazolin-2,5(1H,6H)-Diones (HHQs), K3AlF6(Al2O3/KF), 1,3-Cylohexadione, Acetonitrile

Full-Text   Cite this paper   Add to My Lib

Abstract:

A protocol for the synthesis of some 4-Aryl-1,3,4,6,7,8-hexahydroquinazolin-2,5(1H,6H)-diones (HHQs) was developed by means of a three-component condensation reaction of an aromatic aldehyde, 1,3-cylohexadione and urea in the presence of K3AlF6 (Al2O3/KF) as catalyst. This reaction is carried out under different conditions including 1) solvent free; 2) reflux in acetonitrile; 3) reflux in ethanol; 4) reflux in chloroform; and 5) reflux in water. In all conditions, the desired products are obtained in high yields after relatively short reaction times. Nevertheless, the reactions proceed faster and in higher yields when they were carried out in acetonitrile. This adopted protocol for some Biginelli-type products has offered the advantages of reusability of the catalyst, high yields and ease of separation of pure products. Furthermore, the catalyst is easily prepared, stabilized and efficiently used under reaction conditions.

References

[1]  Nakamichi, N., Kawashita, Y. and Hayashi, M. (2002) Oxidative Aromatization of 1,3,5-Trisubstituted Pyrazolines and Hantzsch 1,4-Dihydropyridines by Pd/C in Acetic Acid. Organic Letters, 4, 3955-3957. https://doi.org/10.1021/ol0268135
[2]  Nakamichi, N., Kawashita, Y. and Hayashi, M. (2004) Activated Carbon-Promoted Oxidative Aromatization of Hantzsch 1,4-Dihydropyridines and 1,3,5-Trisubstituted Pyrazolines Using Molecular Oxygen. Synthesis, 2004, 1015-1020.
[3]  Bonsignore, L., Loy, G., Secci, D. and Calignano, A. (1993) Synthesis and Pharmacological Activity of 2-Oxo-(2H) 1-Benzopyran-3-Carboxamide Derivatives. European Journal of Medicinal Chemistry, 28, 517-520.
https://doi.org/10.1016/0223-5234(93)90020-F
[4]  Hatakeyama, S., Ochi, N., Numataand, H. and Takano, S. (1988) A New Route to Substituted 3-Methoxycarbonyldihydropyrans; Enantioselective Synthesis of (-)- Methyl Elenolate. Journal of the Chemical Society, Chemical Communications, 1202.
https://doi.org/10.1039/C39880001202
[5]  Gonzalez, R., Martin, N., Seoane, C., Marco, J.L., Albert, A. and Cano, F.H. (1992) The First Asymmetric Synthesis of Polyfunctionalized 4H-Pyrans via Michael Addition of Malononitrile to 2-Acyl Acrylates. Tetrahedron Letters, 33, 3809-3812.
[6]  Kappe, C.O. (2000) Biologically Active Dihydropyrimidones of the Biginelli-Type— A Literature Survey. European Journal of Medicinal Chemistry, 35, 1043-1052.
https://doi.org/10.1016/S0223-5234(00)01189-2
[7]  Atwal, K.S., Rovnyak, G.C., Schwartz, J., Moreland, S., Hedberg, A., Gougoutas, J.Z., Malley, M.F. and Floyd, D.F. (1990) Dihydropyrimidine Calcium Channel Blockers: 2-Heterosubstituted 4-Aryl-1,4-Dihydro-6-Methyl-5-Pyrimidinecarboxylic Acid Esters as Potent Mimics of Dihydropyridines. Journal of Medicinal Chemistry, 33, 1510-1515.
https://doi.org/10.1021/jm00167a035
[8]  Kappe, C.O. (1993) 100 Years of the Biginelli Dihydropyrimidine Synthesis. Tetrahedron, 49, 6937-6963. https://doi.org/10.1016/S0040-4020(01)87971-0
[9]  Patil, A.D., Kumar, N.V., Kokke, W.C., Bean, M.F., Freyer, A.J., Debrosse, C., Mai, S., Trunch, A., Faulkner, D.J., Carte, B., Been, A.L., Herzberg, R.P., Johnson, R.K., Wastly, J.W. and Ports, B.C.M. (1995) Novel Alkaloids from the Sponge Batzella sp.: Inhibitors of HIV gp120-Human CD4 Binding. Journal of Organic Chemistry, 60, 1182.
https://doi.org/10.1021/jo00110a021
[10]  Atwal, K.S., Swanson, B.N., Unger, S.E., Floyd, D.M., Moreland, S., Hedberg, A. and O’Reilly, B.C. (1991) Dihydropyrimidine Calcium Channel Blockers. 3-Carbamoy l-4-Aryl-1,2,3,4-Tetrahydro-6-Methyl-5-Pyrimidinecarboxylic Acid Esters as Orally Effective Antihypertensive Agents. Journal of Medicinal Chemistry, 34, 806.
https://doi.org/10.1021/jm00106a048
[11]  Jalali, M., Mahdavi, M., Memarian, H.R., Ranjbar, M., Soleymani, M., Fassihi, A. and Abedi, D. (2012) Antimicrobial Evaluation of Some Novel Derivatives of 3,4- Dihydropyrimidine-2(1H)-One. Research in Pharmaceutical Sciences, 7 243.
[12]  Biginelli, P. (1893) Aldehyde-Urea Derivatives of Aceto- and Oxaloacetic Acids. Gazzetta Chimica Italiana, 23, 360-413.
[13]  Kidwai, M., Saxena, S., Khan, M.K.R. and Thukral, S.S. (2005) Synthesis of 4-Aryl-7,7-Dimethyl-1,2,3,4,5,6,7,8-Octahydroquinazoline-2-One/Thione-5-One Derivatives and Evaluation as Antibacterials. European Journal of Medicinal Chemistry, 40, 816-819.
https://doi.org/10.1016/j.ejmech.2005.02.009
[14]  Shah, P. and Patel, M. (2012) Zn(OTf)2-Catalyzed Three Component, One-Pot Cyclocondensation Reaction of Some New Octahydroquinazolinone Derivatives and Access Their Bio-Potential. Medicinal Chemistry Research, 21, 1188-1198.
https://doi.org/10.1007/s00044-011-9628-y
[15]  Yarim, M., Sarac, S., Kilic, F.S. and Erol, K. (2003) 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-Octahy-droquinazoline-2,5-Dione Derivatives. Farmaco, 58, 17-24.
[16]  Lin, H., Zhao, Q., Xu, B. and Wang, X. (2007) Nafion-H Catalyzed Cyclocondensation Reaction for the Synthesis of Octahydroquinazolinone Derivatives. Journal of Molecular Catalysis A: Chemical, 268, 221-226.
https://doi.org/10.1016/j.molcata.2006.12.020
[17]  Kantevari, S., Bantu, R. and Nagarapu, L. (2006) TMSCl Mediated Highly Efficient One-Pot Synthesis of Octahydroquinazolinone and 1,8-Dioxo-Octahydroxanthene Derivatives. Archive for Organic Chemistry, 2006, 136-148.
[18]  Farhadi, A., Takassi, M.A. and Hejazi, L. (2017) One-Pot Synthesis of 2-Oxo-1,2,3, 4-Tetrahydropyrimidines Using Homogeneous Catalyst under Solvent-Free Conditions. Iranian Chemical Communication, 5, 35-41.
[19]  Clark, J.H. (1980) Fluoride Ion as a Base in Organic Synthesis. Chemical Reviews, 80, 429-452.
https://doi.org/10.1021/cr60327a004
[20]  Yamawaki, J. and Ando, T. (1980) Potassium Fluoride on Alumina as Base for Crown Ether Synthesis. Chemistry Letters, 9, 533-536.
[21]  Yamawaki, J., Ando, T. and Hanafusa, T. (1981) N-Alkylation of Amides and N-Heterocycles with Potassium Fluoride on Alumina. Chemistry Letters, 10, 1143.
https://doi.org/10.1246/cl.1981.1143
[22]  Ando, T., Yamawaki, J., Kawate, T., Sumi, S. and Hanafusa, T. (1982) Fluoride Salts on Alumina as Reagents for Alkylation of Phenols and Alcohols. Bulletin of the Chemical Society of Japan, 55, 2504-2507. https://doi.org/10.1246/bcsj.55.2504
[23]  Clark, J.H., Cork, D.G. and Robertson, M.S. (1983) Fluoride Ion Catalysed Michael Reactions. Chemistry Letters, 12, 1145-1148.
[24]  Yamawaki, J. and Ando, T. (1979) Potassium Fluoride on Inorganic Solid Supports. A Search for Further Efficient Reagents Promoting Hydrogen-Bond-Assisted Alkylation. Chemistry Letters, 8, 755-758. https://doi.org/10.1246/cl.1979.755
[25]  Weinstock, L.M. and Stevensona, J.M. (1986) Characterization of the Actual Catalytic Agent in Potassium Fluoride on Activated Alumina Systems. Tetrahedron Letters, 27, 3845-3848.
https://doi.org/10.1016/S0040-4039(00)83895-2
[26]  Grojtheim, K., Holm, J.L. and Mikhael, S.A. (1973) Equilibrium Studies in the Systems K3AlF6-Na3AlF6 and K3AlF8-Rb3AlF6. Acta Chemica Scandinavica, 27, 1299.
https://doi.org/10.3891/acta.chem.scand.27-1299
[27]  Steward, E.G. and Rooksby, H.P. (1953) Transitions in Crystal Structure of Cryolite and Related Fluorides. Acta Crystallographica, 6, 49.
https://doi.org/10.1107/S0365110X53000107
[28]  Wang, S.X., Li, J.T., Yang, W.Z. and Li, T.S. (2002) Synthesis of Ethyl α-Cyanocin-namates Catalyzed by KF-Al2O3 under Ultrasound Irradiation. Ultrasonics Sonochemistry, 9, 159-161.
https://doi.org/10.1016/S1350-4177(01)00115-8
[29]  Farhadi, A., Ramyar, M. and Takassi, M.A. (2017) Nano Al2O3/KF Using for Synthesis of Some Hantzsch Type-Products. Iranian Chemical Communication. (In Press)
[30]  Ghassamipour, S. and Sardarian, A.R. (2010) One-Pot Synthesis of Dihydropyrimidinones by Dodecylphosphonic Acid as Solid Bronsted Acid Catalyst under Solvent-Free Conditions via Biginelli Condensation. Journal of the Iranian Chemical Society, 7, 237-242.
https://doi.org/10.1007/BF03245884

Full-Text

comments powered by Disqus