Performance analysis and model-free design of deracemisation via temperature-cycles

Solid-state deracemisation via temperature-cycles is a technique that has 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 optimisation. On the other hand, the design space is so large that the experimental optimisation of the process can become long and cumbersome. In this work we achieve two results. First, we show that deracemisation 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). Secondly, we propose a new approach for the design of an effective deracemisation 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 deracemisation via T-cycles for the new compounds, CPG and tLEU, and for $N$-(2-methylbenzylidene)-phenylglycine amide (NMPA) already studied in a previous paper. Based on these outcomes, we conclude by proposing a model-free screening strategy for the design of an effective deracemisation process via temperature-cycles for a new compound.

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