Applying density functional theory on tautomerism in 3,4-dihydropyrimidin-2(1H)-ones

Abstract

In the present study, the density functional theory (DFT) and Gibbs free energy calculations were performed to investigate the stability and tautomerism of C4-substituted-3,4-dihydropyrimidin-2(1H)-ones. Three different forms are possible for the ethyl 3,4-dihydropyrimidinones (ethyl 4-aryl-6-methyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylates, ethyl 4-aryl-2-hydroxy-6-methyl-1,4-dihydropyrimidine-5-carboxylates and ethyl 4-aryl-2-hydroxy-6-methyl-3,4-dihydropyrimidine-5-carboxylates) forms that the most stable form is ethyl 4-aryl-6-methyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylates (keto-form). The obtained data showed that the substitution on the C4-substitut position can be effective on the equilibrium constant (K_eq).

Keywords

Gibbs free energy / density functional theory (DFT) / tautomerism / dihydropyrimidin-2(1H)-ones / Keto-Form

References

[1] Biginelli,P., Gazz. Chim. Ital.1898, 23, 360–413

[2] Cho,H.; Ueda,M.; Shima,K.; Mizuno,A.; Hayashimatsu,M.; Ohnaka,Y.; Takeuchi,Y.; Hamaguchi,M.; Aisaka,K.; Hidaka,T.; Noguchi,T., J. Med. Chem.1989, 32, 2399–2406

[3] Atwal,K. S.; Rovnyak,G. C.; Kimball,S. D.; Floyd,D. M.; Moreland,S.; Swanson,B. N.; Gougoutas,J. Z.; Schwartz,J.; Smillie,K. M.; Malley,M. F., J. Med. Chem.1990, 33, 2629–2635

[4] Rovnyak,G. C.; Kimball,S. D.; Beyer,B.; Cucinotta,G.; DiMarco,J. D.; Gougoutas,J.; Hedberg,A. O.; Malley,M.; McCarthy,J. P.; Zhang,R.; Moreland,S., J. Med. Chem.1995, 38, 119–129

[5] Atwal,K. S.; Swanson,B. N.; Unger,S. E.; Floyd,D. M.; Moreland,S.; Hedberg,A. O.; O’Reilly,B. C., J. Med. Chem.1991, 34, 806–811

[6] Grover,G. J.; Dzwonczyk,S.; McMullen,D. M.; Normandin,D. E.; Parham,C. S.; Sleph,P. G.; Moreland,S., J. Cardiovasc. Pharmacol.1995, 26, 289–294

[7] Memarian,H. R.Farhadi,A.; Sabzyan,H.; Soleymani,M., J. Photochem. Photobiol. Chem.2010, 209, 95–103

[8] Memarian,H. R.; Sabzyan,H.; Farhadi,A., Z. Naturforsch.2009, 64b, 532–540

[9] Memarian,H. R.; Sabzyan,H.; Farhadi,A., Monatsh. Chem.2010, 141, 1203–1212

[10] Kappe,C. O.; Fabian,M. F., Tetrahedron1997, 53, 2803–2816

[11] Kappe,C. O.; Peters,K.; Peters,E. M., J. Org. Chem.1997, 62, 3109–3118

[12] Dondoni,A.; Massi,A.; Minghini,E.; Sabbatini,S.; Bertolasi,V., J. Org. Chem.2003, 68, 6172–6183

[13] Marubayashi,N.; Ogawa,T.; Hamasaki,T.; Hirayama,N., J. Chem. Soc., Perkin Trans. 21997, 1309–1314

[14] Ozimiński,W. P.; Dobrowolski,J. C.; Mazurek,A. P., J. Mol. Struct. THEOCHEM2004, 680, 107–115

[15] Trofimenko,S.; Yap,G. P. A.; Jove,F. A.; Claramunt,R. M.; García,M. Á.; Santa Maria,M. D.; Alkorta,I.; Elguero,J., Tetrahedron2007, 63, 8104–8111

[16] Alkorta,I.; Blanco,F.; Elguero,J., Tetrahedron2010, 66, 5071–5081

[17] Kappe,C. O., Tetrahedron1993, 49, 6937–6963

[18] Dondoni,A.; Massi,A., Tetrahedron Lett.2001, 42, 7975–7978

[19] Mandhane,P. G.; Joshi,R. S.; Nagargoje,D. R.; Gill,C. H., Tetrahedron Lett.2010, 51, 3138-3140

[20] Frisch,M. J.; Trucks,G. W.; Schlegel,H. B.; Scuseria,G. E.; Robb,M. A.; Cheeseman,J. R.; Zakrzewski,V. G.; Montgomery,J. A. Jr; Stratmann,R. E.; Burant,J. C.; Dapprich,S.; Millam,J. M.; Daniels,A. D.; Kudin,K. N.; Strain,M. C.; Farkas,O.; Tomasi,J.; Barone,V.; Cossi,M.; Cammi,R.; Mennucci,B.; Pomelli,C.; Adamo,C.; Clifford,S.; Ochterski,J.; Petersson,G. A.; Ayala,P. Y.; Cui,Q.; Morokuma,K.; Malick,D. K.; Rabuck,A. D.; Raghavachari,K.; Foresman,J. B.; Ciolowski,J.; Ortiz,J. V.; Stefanov,B. B.; Liu,G.; Liashenko,A.; Piskorz,P.; Komaromi,I.; Gomperts,R.; Martin,R. L.; Fox,D. J.; Keith,T.; Al-Laham,M. A.; Peng,C. Y.; Nanayakkara,A.; Gonzalez,C.; Challacombe,M.; Gill,P. M. W.; Johnson,B.; Chen,W.; Wong,M. W.; Andres,J. L.; Head-Gordon,M.; Replogle,E. S.; Pople,J. A., Gaussian 98, Gaussian Inc., Pittsburg PA, 1998

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg