Performance Analysis and Model-Free Design of Deracemization via Temperature Cycles

Abstract

Solid-state deracemization via temperature cycles is a technique that has been shown to be effective to isolate the pure enantiomer of a conglomerate-forming compound. This process has a large number of operating parameters that can be adjusted according to system-specific properties. On the one hand, this feature makes the process flexible and prone to optimization. On the other hand, the design space is so large that experimental optimization of the process can become long and cumbersome. In this work, we achieve two results. First, we show that deracemization via temperature cycles works very effectively for two new experimental systems, namely, the chiral compounds 2-(benzylideneamino)-2-(2-chlorophenyl)acetamide (CPG) and 3,3-dimethyl-2-((naphthalen-2-ylmethylene)amino)butanenitrile (tLEU). Second, we propose a new approach for the design of an effective deracemization process via temperature cycles for a new compound. Therefore, in this work, we investigate the effect of different operating conditions, namely, the initial enantiomeric excess, the cooling rate, the temperature range, and the catalyst concentration, on the performance of deracemization via temperature cycles for the new compounds CPG and tLEU and for N-(2-methylbenzylidene)phenylglycine amide (NMPA), which was already studied in a previous paper. On the basis of these outcomes, we conclude by proposing a model-free screening strategy for the design of an effective deracemization process via temperature cycles for a new compound.