Computational Study on the Energetic and Electronic Aspects of Tautomeric Equilibria in 5-methylthio-1,2,4-triazole

Document Type : Regular Article


Department of Chemistry, Faculty of Science, Alzahra University, Vanak, Tehran, Iran


The main purpose of this research is to investigate computationally the tautomeric reaction pathway of 5-methyl-3-methylthio-1,2,4-triazole from the thermodynamical and mechanistical viewpoints. In this respect, density functional theory (DFT) in conjunction with the quantum theory of atoms in molecule (QTAIM) has been employed to model the energetic and electronic features of tautomeric mechanism in the gas phase. Moreover, the effect of two different solvents, dimethylformamide (DMF) and H2O, has been examined via the polarized continuum model (PCM) calculations. Then we have presented the potential energy profile for the two-step tautomeric reaction in the gas and solution phases and analyzed comparatively the energetic aspects of tautomers, intermediate and transition states. On the other hand, we have concentrated on the survey of tautomerism by means of topological electronic indices. Strictly speaking, QTAIM calculations have been performed to explore the variation of electronic density and its laplacian at some key bond critical points of tautomers, intermediate and transition states and also to interpret the proposed tautomeric mechanism.

Graphical Abstract

Computational Study on the Energetic and Electronic Aspects of Tautomeric Equilibria in 5-methylthio-1,2,4-triazole


Main Subjects

[1] A.R. Katritzky, C.A. Ramsden, J.A. Joule, V.V. Zhdankin, Handbook of Heterocyclic Chemistry, 3rd ed., Elsevier, Oxford, 2010.
[2] A.R. Katritzky, C.A. Ramsden, E.F.V. Scriven, R.J.K. Taylor, Comprehensive Heterocyclic Chemistry-III, Elsevier, Oxford, 2008.
[3] M.D. Mullican, M.W. Wilson, D.T. Connor, C.R. Kostlan, D.J. Schrier, R.D. Dyer, J. Med. Chem. 36 (1993) 1090.
[4] E. Bozo, G. Szilagyi, A. Janaka, J. Arch. Pharm. 322 (1989) 583.
[5] D.H. Boschelli, D.T. Connor, D.A. Bornemeier, R.D. Dyer, J.A. Kennedy, P.J. Kuipers, G.C. Okonkwo, D.J. Schrier, C.D. Wright, J. Med. Chem. 36 (1993) 1802.
[6] R.W. Taft, F. Anvia, M. Taagepera, J. Catalfin, J.  Elguero, J. Am. Chem. Soc. 108 (1986) 3237.
[7] J. Elguero, A.R. Katritzky, O.V. Denisko, Adv. Heterocycl. Chem. 76 (2000) 1.
[8] E.D. Raczynska, W. Kosinska, B. Osmiatowski, R. Gawinecki, Chem. Rev. 105 (2005) 3561.
[9] M.M. Heravi, A. Kivanloo, M. Rahimzadeh, M. Bakavoli, M. Ghassemzadeh, B. Neumüller, Tetrahedron Lett. 46 (2005) 1607.
[10] M.M. Heravi, H.R. Khademalfoghara, M.M. Sadeghi, Sh. Khaleghi, M. Ghassemzadeh, Phosphorus, Sulfur Silicon Relat. Elem. 181 (2006) 377.
[11] M.M. Heravi, A. Kivanloo, M. Rahimzadeh, M. Bakavoli, M. Ghassemzadeh, Phosphorus, Sulfur, Silicon Relat. Elem. 177 (2002) 2491.
[12] T. Hosseinnejad, M.M. Heravi, R. Firouzi, J. Mol. Model. 19 (2013) 951.
[13] A.D. Becke, J. Chem. Phys. 98 (1993) 1372.
[14] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B. 37 (1988) 785.
[15] D.G. Truhlar, Y. Zhao, Theor. Chem. Account. 120 (2008) 215.
[16] V. Barone, M. Cossi, M. J. Phys. Chem. A 102 (1998) 1995.
[17] M.M. Heravi, S. Sadjadi, Tetrahedron 65 (2009) 7761.
[18] C. Amatore, E. Carré, A. Jutand, A. Acta Chem. Scand. 52 (1998) 100.
[19] R.F.W. Bader, Atoms in Molecules: a Quantum Theory, Oxford University Press, Oxford, 1990.
[20] M.W. Schmidt, K.K. Baldridge, J.A. Boatz, S.T. Elbert, M.S. Gordon, J.H. Jensen, S. Koseki, N. Matsunaga, K.A. Nguyen, S.J. Su, T.L. Windus, M. Dupuis, J.A. Montgomery, J. Comput. Chem. 14 (1993) 1347.
[21] C. Gonzales, H.B. Schlegel, J. Chem. Phys. 90 (1989)
2154. [22] C. Gonzales, H.B. Schlegel, J. Chem. Phys. 95 (1991) 5853.
[23] R.F.W. Bader, AIM2000 Program, ver 2.0, Hamilton, McMaster University, 2000.
[24] R.F.W. Bader, Chem. Rev. 91 (1991) 893.
[25] D. Cremer, E. Kraka, Angew. Chem. 23 (1984) 627.
[26] K. Wiberg, Tetrahedron 24 (1968) 1093.
[27] S. Jenkins, I. Morrison, Chem. Phys. Lett. 317 (2000) 97.
Volume 1, Issue 2 - Serial Number 2
December 2013
Pages 175-184
  • Receive Date: 20 July 2013
  • Revise Date: 14 September 2013
  • Accept Date: 17 September 2013
  • First Publish Date: 01 December 2013