Investigation of temperature cycling with coupled vessels for efficient deracemization of NMPA

Abstract

Chiral compounds can exist as pairs of nonsuperimposable stereoisomers (enantiomers) possessing the same physical properties but interacting differently with biological systems. This makes them interesting materials to be explored by the pharmaceutical and food industries. In this study, to obtain pure enantiomers from their conglomerates, a method that involves using a two-vessel system for deracemization of N-(2-methylbenzylidene) phenylglycine amide (NMPA) was developed. In this method, a suspension was transferred with a pulsating pumping profile between two inter-connected stirred vessels that were set at constant temperatures. As the suspension was exposed to more rapid changes in temperature, it resulted in the speeding up of the process and thus enhancing productivity in comparison to a single vessel system. The results confirmed successful deracemization of NMPA. A modified pumping profile and tubing design eliminated the issue of clogging of the transfer tubes and ensured effective suspension transfer for longer durations. Operating parameters, such as initial enantiomeric excess, vessel residence time, and suspension density were also investigated. In this method, optimization of residence time was necessary to enhance the efficiency of the process further. Results confirmed that this methodology has the potential to be more adaptable and scalable as it involved no mechanical attrition.