A computational study on phenibut lactamization mechanism and the pH effects on the process

Abstract

The current work investigates the lactamization reaction of neuropsychotropic medicine phenibut to higher toxicity phenibut-lactam. The reaction is considered as an intramolecular cyclization which finally leads to generation of phenibut-lactam component. Herein, we considered three different structural forms for the chemically intact phenibut which consist of two stable R1, R2, and a relatively distorted isomer R*. The initial stage in this reaction is the transformation of two stable isomers into the unstable form, R*. The calculations showed that there is a transition state (TS) close to the unstable geometry, R*. This transition state possesses 31.30 kcal/mol more energy compared to the isomer R* (5.98 kcal/mol). By studying the thermodynamic stability of the lactam structure (− 13.55 kcal/mol), we can clearly conclude that pheni-l component has higher thermal stability compared to its related phenibut. Also, from the investigation of this reaction in various pH, it was found that the rate of reaction reduces under both basic and acidic conditions.