Quantum-chemical calculations of transitional states thermodynamic parameters of tautomers of initial N,N’-disubstituted thiourea derivative during the cyclization reaction in the conditions of different solvents application

Perekhoda, L. O.; Yeromina, H. O.; Ieromina, Z. G.; Sheykina, N. V.; Krasovskyi, I. V.; Krasovska, M. V.; Storozhenko, I. P.

doi:10.7124/bc.000A19

Biopolym. Cell. 2019; 35(6):467-475.

http://dx.doi.org/10.7124/bc.000A19

Molecular Biophysics

Quantum-chemical calculations of transitional states thermodynamic parameters of tautomers of initial N,N’-disubstituted thiourea derivative during the cyclization reaction in the conditions of different solvents application

1Perekhoda L. O., 1Yeromina H. O., 1Ieromina Z. G., 1Sheykina N. V., 1Krasovskyi I. V., 2Krasovska M. V., 1Storozhenko I. P.

National University of Pharmacy
53, Pushkinska Str., Kharkiv, Ukraine, 61002
SSI "Institute for Single Crystals", NAS of Ukraine
60, Nauky ave., Kharkiv, Ukraine, 61001

Abstract

Aim. Theoretical substantiation of the cyclization reaction possible direction in different solvents by means of quantum-chemical calculations of thermodynamic parameters of three tautomers of the initial N-ethyl-N’-[4-(6,7,8,9-tetrahydro-5H-[1,2,4]triazol[4,3-a]azepin-3-yl)phenyl]thiourea. Methods. Quantum-chemical calculations of relative energies, interconversion barriers, structural and thermodynamic parameters of tautomers of the initial thiourea in dioxane, ethanol, dimethylformamide (DMFA) and tetrachlormethane were performed on the basis of the density functional theory applying the GAUSSIAN 09W program. The influence of the solvent was taken into account within the framework of the continuum polarized model. Results. According to the results obtained, in all the solvents under study the cyclization reaction must proceed in one direction to form the N-ethyl-4-phenyl-N’-[4-(6,7,8,9-tetrahydro-5H-[1,2,4]triazol[4,3-a]azepin-3-yl) phenyl]-1,3-thiazole-2(3H)-imine. The smallest barrier of initial thiourea tautomers interconversion was observed in the condition of dioxane application as a solvent, this fact indicated the advantage of synthesis conducting in this solvent precisely in comparison to ethanol, water, tetrachlormethane and DMFA. Conclusions. It is theoretically justified that dioxane is the most suitable solvent for cyclization.

Keywords: 5Y-[1,2,4]triazol[4,3-a]azepines, cyclization, quantum-chemical calculations, activating energy, relative energy, saddle point (transitional state)

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