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

Abstract

An important step in the creation of potential drugs is to confirm the structure of the synthesized compounds. This requires the use of modern physical and physicochemical methods. Nowadays a perspective scientific direction for searching biologically active substances is the study of 2-R-imino-1,3-thiazoline derivatives. The purpose of the present work is to study a regioselectivity of cyclization of 1-ethyl-3-[4-(6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-а]azepin-3-yl)phenyl]thiourea reaction with 2-bromo-1-phenylethanone. Results and discussion. The structure of the interaction product was determined by the methods 1H NMR spectroscopy and X-ray analysis. 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. So we can make the conclusion that the reaction will go by the way 1-1A-3A. Experimental part. Quantum-chemical calculations of electronic structure, geometry and thermodynamics parameters of initial thiourea three tautomers were calculated with the density functional theory (DFT) methods using the GAUSSIAN W09 computer program. The effect of the solvent was considered out 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-5Н-[1,2,4]triazolo[4,3-а]azepin-3-yl)phenyl]thiourea 1 with 2-bromo-1-phenylethanone 2 is regioselective and leads to formation of more thermodynamically advantageous isomer 3A.