SYNTHESIS AND THERMOCHEMICAL MODELING OF REACTION MECHANISM FOR PRODUCING N-ACYL DERIVATIVES OF 2-(2-OXO-1-PYRROLIDINE-1-YL) – ACETAMIDE

Abstract

Nootropic drugs are an extensive group of drugs that are used in the treatment of various disorders of the сentral nervous system. One of the widely used nootropic medicines is a piracetam, which is a cyclic derivative of γ-aminobutyric acid. Synthesis of new derivatives of the piracetam with a high nootropic activity is a promising direction of creation of new neuroprotective drugs. The aim of this work is to optimize the synthesis method and the computer calculation of the thermodynamic parameters, explaining the yields of the reaction to obtain N-acyl derivatives of 2-(2-oxo-1-pyrrolidine-1-yl) - acetamide. The acylation of 2-(2-oxo-1-pyrrolidine-1-yl) - acetamide (piracetam) was made by his interaction with anhydrides of organic acids, which are differed in a long carbon chain. The UB3LYP density functional theory method with 6-311G**basis sets was used to determine the thermodynamic properties of molecules. The resulting vibrational analysis of the studied thermodynamic characteristics was carried out in the Orca program. The values of enthalpy, entropy and Gibbs energy were calculated for each stage of the reaction mechanism. Determination of impurities in the reaction products was carried out by HPLC using the UltiMate 3000 system (Dionex, USA) with a spectrophotometric detector covering the operating wavelength range in the region from 190 to 900 nm. The collection and processing of data were carried out by the system for processing chromatographic data Сhromeleon, version 7, using Dionex, USA. The obtained values of the yields of N-acylamides of piracetam to some extent are explained by the calculations of the thermodynamic characteristics of computational methods of computer chemistry (enthalpy, entropy, Gibbs energy, equilibrium constant). Spectral methods of research proved the structure of the compounds and their high purity was determined using HPLC, which confirms the feasibility of using the proposed method of preparation.