Study of stability of potential betaadrenolytics, derivatives of the [(arylcarbonyl)oxy]aminopropanol by kinetics of alkaline hydrolysis

Abstract

This work deals with the study of the stability of six derivatives of the [(arylcarbonyl)oxy]amino propanol with carbamate substitution on the benzene ring. The studied compounds are different in the substitution on the amine group in the side chain as well as in the substitution on the carbamate functional group. The hydrolysis of compounds was measured in the aqueous-ethanol sodium hydroxide solution (0.1 mol.l -1 ) at 25, 37, 45 and 60°C spectrophotometrically in the ultraviolet and visual regions. The studied compounds possess two functional groups, which undergo hydrolysis. The pseudo-first order rate constants of hydrolysis for individual reaction steps were determined. The ester functional group of compounds hydrolyses very quickly in this medium. The compounds possessing the tertiary substitution on the amino group are less stable toward alkaline hydrolysis. The course of hydrolysis of compounds was also investigated by thin layer chromatography (TLC).

Evaluation of Stability of Potential Betaadrenolytics in Various Solutions by thin Layer Chromatography and by Kinetics of Hydrolysis

“…The ultra-short beta-blocking activity of the prepared derivatives was attained by the incorporation of metabolically unstable ester functional group into the connecting chain of the original aryloxypropanolamine structure of the beta-blockers. The substitution on the nitrogen atom of amino group of these drugs differs from that of compounds studied in (Stankovičová, 2011). The hydrogen atom of the amine group is substituted with the phenylethylene group where on the benzene ring is placed in position 2-or in position 4-a methoxy group.…”