Characterization of rates of growth and dissolution of crystals of conglomerate-forming chiral compounds

The two characteristics of enantiomer crystals of conglomerates, i.e., identical properties and enantiomerically pure crystal lattices, allow us to develop a novel experimental protocol to estimate the kinetics of crystal dissolution and crystal growth of conglomerate forming chiral compounds. This is based on measuring the evolution of the enantiomeric excess of a suspension initially enriched in one of the enantiomers during one heating and cooling cycle, and on estimating dissolution and growth rate parameters by fitting the enantiomeric excess measurements using the population balance equation model. The protocol is used to characterize the temperature-independent rates of growth and dissolution of three compounds, namely N-(2-methylbenzylidene)-phenylglycine amide (NMPA), 2-(benzylideneamino)-2-(2-chlorophenyl)acetamide (CPG) and 3,3-dimethyl-2-((naphthalen-2-ylmethylene)amino) butanenitrile (tLEU). All three compounds have been demonstrated in the literature to be amenable to solid-state deracemization via periodic temperature cycling. In this work, we show that random temperature fluctuations lead to complete deracemization also of CPG and tLEU, likewise what is already reported for NMPA. The two novel pieces of experimental evidence provided in this work, namely that dissolution is faster than growth and that CPG and tLEU (as well as NMPA) are solid-state-deracemized by random temperature fluctuations, are fully consistent with the theoretical findings about a simple and ubiquitous criterion for solid-state deracemization that we have recently demonstrated. • Development of a novel experimental protocol to estimate the crystal dissolution and crystal growth kinetics of conglomerates. • Demonstration of faster crystal dissolution than crystal growth. • Solid-state deracemization of two chiral model compounds via random temperature fluctuations.