DFT Studies of Synthesis of (4R,5S,8as)-4,5,8a-Triphenylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3H)-dione

Qi-Shan Hu; Yun-Qing He; Lai-Cai Li

doi:10.14233/ajchem.2016.19641

Issue

Vol. 28 No. 6 (2016): Vol 28 Issue 6

Issue Published : February 29, 2016

This work is licensed under a Creative Commons Attribution 4.0 International License.

DFT Studies of Synthesis of (4R,5S,8as)-4,5,8a-Triphenylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3H)-dione

https://doi.org/10.14233/ajchem.2016.19641

Qi-Shan Hu

College of Chemistry and Chemical Engineering, Sichuan University of Arts and Science, Dazhou 635711, P.R. China

Yun-Qing He

College of Chemistry, Leshan Normal University, Leshan 614000, P.R. China

Lai-Cai Li

College of Chemistry, Leshan Normal University, Leshan 614000, P.R. China

Corresponding Author(s) : Qi-Shan Hu

huqs@163.com

Asian Journal of Chemistry, Vol. 28 No. 6 (2016): Vol 28 Issue 6
Article Published : February 29, 2016

Abstract

The mechanism of one-pot reaction of benzaldehyde, urea and acetophenone for the synthesis of (4R,5S,8as)-4,5,8a-triphenylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3H)-dione catalyzed by protonic acid was investigated by density functional theory (DFT). The geometries and the frequencies of reactants, intermediates, transition states and products were calculated at the B3LYP/6-311G(d) level. The vibration analysis and the IRC analysis verified the authenticity of transition states. The reaction processes were confirmed by the changes of charge density at the bond-forming critical point. The results indicated that protonic acid is an effective catalyst in the synthesis of (4R,5S,8as)-4,5,8a-triphenylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3H)-dione from benzaldehyde, urea and acetophenone. The activation energy of reaction with protonic acid decreased by 104.3 kJ mol^-1 compared with that of the reaction without it. The mechanism of reaction with catalyst protonic acid differs from that of reaction without it.

Keywords

Density functional theory Biginelli reaction Dihydropyrimidone

Hu, Q.-S., He, Y.-Q., & Li, L.-C. (2016). DFT Studies of Synthesis of (4R,5S,8as)-4,5,8a-Triphenylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3H)-dione. Asian Journal of Chemistry, 28(6), 1244–1252. https://doi.org/10.14233/ajchem.2016.19641

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References

P. Biginelli, Ber. Dtsch. Chem. Ges., 24, 1317 (1891); doi:10.1002/cber.189102401228.
A. Klages and E. Knoevenagel, Ber. Dtsch. Chem. Ges, 26, 447 (1893); doi:10.1002/cber.18930260199.
C.O. Kappe, Bioorg. Med. Chem. Lett., 10, 49 (2000); doi:10.1016/S0960-894X(99)00572-7.
X.H. Chen, X.Y. Xu, H. Liu, L.F. Cun and L.Z. Gong, J. Am. Chem. Soc., 128, 14802 (2006); doi:10.1021/ja065267y.
V. Polshettiwar and R.S. Varma, Tetrahedron Lett., 48, 7343 (2007); doi:10.1016/j.tetlet.2007.08.031.
L.Z. Gong, X.H. Chen and X.Y. Xu, Chem. Eur. J., 13, 8920 (2007); doi:10.1002/chem.200700840.
N. Ahmed and J.E. van Lier, Tetrahedron Lett., 48, 5407 (2007); doi:10.1016/j.tetlet.2007.06.005.
A. Debache, M. Amimour, A. Belfaitah, S. Rhouati and B. Carboni, Tetrahedron Lett., 49, 6119 (2008); doi:10.1016/j.tetlet.2008.08.016.
R. Wang and Z.Q. Liu, J. Org. Chem., 77, 3952 (2012); doi:10.1021/jo300282y.
J.H. Clark, D.J. Macquarrie and J. Sherwood, Chem. Eur. J., 19, 5174 (2013); doi:10.1002/chem.201204396.
I. Sehout, R. Boulcina, B. Boumoud, F. Berree, B. Carboni and A. Debache, Lett. Org. Chem., 10, 463 (2013); doi:10.2174/15701786113109990014.
H.G.O. Alvim, T.B. de Lima, H.C.B. de Oliveira, F.C. Gozzo, J.L. de Macedo, P.V. Abdelnur, W.A. Silva and B.A.D. Neto, ACS Catalysis, 3, 1420 (2013); doi:10.1021/cs400291t.
S.R. Alapati, P.K. Pullela, P. Rangappa and V. Pillarisetti, Substituted Dihydropyrimidines, Dihydropyrimidones and Dihydropyrimidinethiones as Calcium Channel Blockers, US Patent, US7687511 B2 (2010)..
K.S. Atwal, B.N. Swanson, S.E. Unger, D.M. Floyd, S. Moreland, A. Hedberg and B.C. O’Reilly, J. Med. Chem., 34, 806 (1991); doi:10.1021/jm00106a048.
G.C. Rovnyak, K.S. Atwal, A. Hedberg, S.D. Kimball, S. Moreland, J.Z. Gougoutas, B.C. O’Reilly, J. Schwartz and M.F. Malley, J. Med. Chem., 35, 3254 (1992); doi:10.1021/jm00095a023.
G.J. Grover, S. Dzwonczyk, D.M. McMullen, D.E. Normandin, C.S. Parham, P.G. Sleph and S. Moreland, J. Cardiovasc. Pharmacol., 26, 289 (1995); doi:10.1097/00005344-199508000-00015.
S. Putatunda, S. Chakraborty, S. Ghosh, P. Nandi, S. Chakraborty, P.C. Sen and A. Chakraborty, Eur. J. Med. Chem., 54, 223 (2012); doi:10.1016/j.ejmech.2012.04.043.
S.S. Kshirsagar and P. Shanmugasundaram, Int. J. Chem. Technol. Res., 5, 2899 (2013).
Y.M. Litvinov, A.A. Shestopalov, L.A. Rodinovskaya and A.M. Shestopalov, J. Comb. Chem., 11, 914 (2009); doi:10.1021/cc900076j.
Z.L. Shen, X.P. Xu and S.J. Ji, J. Org. Chem., 75, 1162 (2010); doi:10.1021/jo902394y.
F. Shi, R.H. Jia, X.J. Zhang, S.J. Tu, S. Yan, Y. Zhang, B. Jiang, J.Y. Zhang and C.S. Yao, Synthesis, 18, 2782 (2007); doi:10.1055/s-2007-983874.
R.F.W. Bader, Atoms in Molecules: A Quantum Theory; Clarendon: Oxford, U.K. (1990).
P.L. Prpelier, Atoms in Molecules: An Introduction; Pearson Education: Halow, U.K. (1999).
M. Takahashi, S. Tsutsui, K. Sakamoto, M. Kira, T. Müller and Y. Apeloig, J. Am. Chem. Soc., 123, 347 (2001); doi:10.1021/ja003463d.
M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez and J.A. Pople, Gaussian, Inc.: Pittsburgh, PA (2003).

References

P. Biginelli, Ber. Dtsch. Chem. Ges., 24, 1317 (1891); doi:10.1002/cber.189102401228.

A. Klages and E. Knoevenagel, Ber. Dtsch. Chem. Ges, 26, 447 (1893); doi:10.1002/cber.18930260199.

C.O. Kappe, Bioorg. Med. Chem. Lett., 10, 49 (2000); doi:10.1016/S0960-894X(99)00572-7.

X.H. Chen, X.Y. Xu, H. Liu, L.F. Cun and L.Z. Gong, J. Am. Chem. Soc., 128, 14802 (2006); doi:10.1021/ja065267y.

V. Polshettiwar and R.S. Varma, Tetrahedron Lett., 48, 7343 (2007); doi:10.1016/j.tetlet.2007.08.031.

L.Z. Gong, X.H. Chen and X.Y. Xu, Chem. Eur. J., 13, 8920 (2007); doi:10.1002/chem.200700840.

N. Ahmed and J.E. van Lier, Tetrahedron Lett., 48, 5407 (2007); doi:10.1016/j.tetlet.2007.06.005.

A. Debache, M. Amimour, A. Belfaitah, S. Rhouati and B. Carboni, Tetrahedron Lett., 49, 6119 (2008); doi:10.1016/j.tetlet.2008.08.016.

R. Wang and Z.Q. Liu, J. Org. Chem., 77, 3952 (2012); doi:10.1021/jo300282y.

J.H. Clark, D.J. Macquarrie and J. Sherwood, Chem. Eur. J., 19, 5174 (2013); doi:10.1002/chem.201204396.

I. Sehout, R. Boulcina, B. Boumoud, F. Berree, B. Carboni and A. Debache, Lett. Org. Chem., 10, 463 (2013); doi:10.2174/15701786113109990014.

H.G.O. Alvim, T.B. de Lima, H.C.B. de Oliveira, F.C. Gozzo, J.L. de Macedo, P.V. Abdelnur, W.A. Silva and B.A.D. Neto, ACS Catalysis, 3, 1420 (2013); doi:10.1021/cs400291t.

S.R. Alapati, P.K. Pullela, P. Rangappa and V. Pillarisetti, Substituted Dihydropyrimidines, Dihydropyrimidones and Dihydropyrimidinethiones as Calcium Channel Blockers, US Patent, US7687511 B2 (2010)..

K.S. Atwal, B.N. Swanson, S.E. Unger, D.M. Floyd, S. Moreland, A. Hedberg and B.C. O’Reilly, J. Med. Chem., 34, 806 (1991); doi:10.1021/jm00106a048.

G.C. Rovnyak, K.S. Atwal, A. Hedberg, S.D. Kimball, S. Moreland, J.Z. Gougoutas, B.C. O’Reilly, J. Schwartz and M.F. Malley, J. Med. Chem., 35, 3254 (1992); doi:10.1021/jm00095a023.

G.J. Grover, S. Dzwonczyk, D.M. McMullen, D.E. Normandin, C.S. Parham, P.G. Sleph and S. Moreland, J. Cardiovasc. Pharmacol., 26, 289 (1995); doi:10.1097/00005344-199508000-00015.

S. Putatunda, S. Chakraborty, S. Ghosh, P. Nandi, S. Chakraborty, P.C. Sen and A. Chakraborty, Eur. J. Med. Chem., 54, 223 (2012); doi:10.1016/j.ejmech.2012.04.043.

S.S. Kshirsagar and P. Shanmugasundaram, Int. J. Chem. Technol. Res., 5, 2899 (2013).

Y.M. Litvinov, A.A. Shestopalov, L.A. Rodinovskaya and A.M. Shestopalov, J. Comb. Chem., 11, 914 (2009); doi:10.1021/cc900076j.

Z.L. Shen, X.P. Xu and S.J. Ji, J. Org. Chem., 75, 1162 (2010); doi:10.1021/jo902394y.

F. Shi, R.H. Jia, X.J. Zhang, S.J. Tu, S. Yan, Y. Zhang, B. Jiang, J.Y. Zhang and C.S. Yao, Synthesis, 18, 2782 (2007); doi:10.1055/s-2007-983874.

R.F.W. Bader, Atoms in Molecules: A Quantum Theory; Clarendon: Oxford, U.K. (1990).

P.L. Prpelier, Atoms in Molecules: An Introduction; Pearson Education: Halow, U.K. (1999).

M. Takahashi, S. Tsutsui, K. Sakamoto, M. Kira, T. Müller and Y. Apeloig, J. Am. Chem. Soc., 123, 347 (2001); doi:10.1021/ja003463d.

M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez and J.A. Pople, Gaussian, Inc.: Pittsburgh, PA (2003).

Issue

Vol. 28 No. 6 (2016): Vol 28 Issue 6

DFT Studies of Synthesis of (4R,5S,8as)-4,5,8a-Triphenylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3H)-dione

Corresponding Author(s) : Qi-Shan Hu

Abstract

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