The presentation of regioselectivity of 1-ethyl-3-[4-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-а]azepin-3-yl)phenyl]thiourea cyclization with α-bromoketone

L. O. Perekhoda; H. O. Yeromina; I. P. Storozhenko; N. V. Sheykina; I. V. Krasovskyi; M. V. Krasovska; S. A. Demchenko

doi:10.24959/ophcj.17.916

Authors

L. O. Perekhoda National University of Pharmacy, Ukraine
H. O. Yeromina National University of Pharmacy, Ukraine
I. P. Storozhenko National University of Pharmacy, Ukraine
N. V. Sheykina National University of Pharmacy, Ukraine
I. V. Krasovskyi National University of Pharmacy, Ukraine
M. V. Krasovska State Scientific Institution “The Institute for Single Crystals”, National Academy of Science of Ukraine, Ukraine
S. A. Demchenko Institute of Pharmacology and Toxicology of the AMS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.17.916

Keywords:

5H-[1, 2, 4]triazolo[4, 3-а]azepines, cyclization, quantum chemical calculations, continuum, activation energy, relative energy, B3LYP/6-31 G(d) and M06-2X/6-31 G(d) GAUSSIAN W09 program methods, thermodynamics parameters, saddle point

Abstract

An important step in creation of potential drugs is to confirm the structure of the compounds synthesized. This requires the use of modern physical and physico-chemical methods of research. Nowadays a promising scientific direction for searching biologically active substances is the study of 2-R-imino-1,3-thiazoline derivatives.

Aim. To study regioselectivity of the cyclization reaction of 1-ethyl-3-[4-(6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-а]azepin-3-yl)phenyl]thiourea with 2-bromo-1-phenylethanone.

Results. The true structure of the interaction product was determined by the methods of ¹H NMR spectroscopy and X-ray analysis. Quantum chemical calculations of the electronic structure, geometry and thermodynamic parameters of the initial thiourea three tautomers were given. Activating energy of tautomer 1A belower than 1B one, the state of 1B has modest lower relative energy, consequently tautomer 1A is more credible state. Thus, the conclusion can be made that the reaction will proceed by 1-1A-3A.

Experimental part. Quantum chemical calculations of the electronic structure, geometry and thermodynamic parameters of the initial thiourea three tautomers were determined by the density functional theory (DFT) methods using the GAUSSIAN W09 computer program. The effect of the solvent was considered within the framework of polarized continuum model (PCM).

Conclusions. Based on the physico-chemical studies and quantum chemical calculations of the reaction cyclization direction the conclusion has been made that the cyclization reaction of 1-ethyl-3-[4-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-а]azepin-3-yl)phenyl]thiourea 1 with 2-bromo-1-phenylethanone 2 is regioselective, and it leads to formation of more thermodynamically advantageous (stable) isomer 3A.

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