Combining Viedma Ripening and Temperature Cycling Deracemization

Abstract

While much data are available for the Viedma ripening and temperature cycling deracemization processes, not much is known about the advantages (or disadvantages) of a combination of the two. We here try to elucidate what happens when Viedma ripening is used in combination with temperature cycling by comparing not only the deracemization times but also the change in the sizes of the crystals. We found that, in the case of NMPA ( rac -(2-methylbenzylidene)-phenylglycine amide) as a model compound, combined experiments significantly increase the deracemization time. By tuning the process parameters, it is possible to approach experimental conditions where both Viedma ripening and temperature cycling control the deracemization. Under those conditions, however, the deracemization time is not significantly improved. Following our results, it seems unlikely that a combination of Viedma ripening and temperature cycling would shorten the deracemization time. Nevertheless, these experiments might provide clues for unraveling the mechanism of temperature cycling.

Possibility of Conversion from a Stable Phase to a Metastable Phase by Grinding Crystals

“…4 in [32]), the conversion by TC is faster than that by VR. In an experiment of the chirality conversion, the conversion time of TC is about 20 times shorter than that of VR [37]. Our result is consistent with the experimental result although direct correspondence between the theoretical and the experimental parameter values cannot be made.…”

Exact and Ubiquitous Condition for Solid-State Deracemization in Vitro and in Nature

“…Although a strong temperature dependence of the racemization rate constant may in theory switch the sign of the inequality in eq 9, in practice, this is very unlikely given the relatively small amplitudes of temperature cycles used in experiments (order of 5−20 °C), 10,11,40 if not at all impossible when considering the very small-amplitude temperaturecycling experiments presented in this work (see Section 2.4).…”

Strategies for chiral separation: from racemate to enantiomer

“…83 However, crystallization possesses the highest compatibility with deracemization (Section 5). This is because the size-dependent solubility difference between two enantiomers can be naturally and easily induced by simple physical processes during crystallization, such as boiling, 84 agitation, 85 temperature cycling, 86 homogenization 87 and grinding, 88 thereby leading to a concentration difference between enantiomers for initializing racemization. Among them, temperature cycling-induced deracemization (TCID) and attrition-enhanced deracemization (VR) are the most widely used autocatalysis-crystallization techniques, which can be coupled with CCR-, CBR- and (reverse) PC-related processes 37,84,89,90 to expand the substrate scope from racemic conglomerates (Con) to racemic compounds (Rac) and racemic solid solutions (Ss).…”