Chiral resolution by preferential crystallization from a racemic or scalemic solution occurs by selective crystallization of a single enantiomer as a homochiral solid phase, known as a conglomerate. However, there is a prevailing perception that stable homochiral crystals are quite rare and are estimated to form in only 510% of all chiral compounds. In this work, the prevalence rate of stable conglomerates is reexamined using dispersion-corrected density-functional theory calculations for a collection of homochiral and heterochiral crystal pairs. The homochiral crystal is found to be the thermodynamically stable phase for 19% of the examined compounds. This value represents a lower bound of the prevalence rate since our sample is necessarily biased because the comparison is limited to cases where a stable heterochiral phase exists and does not include molecules with no reported heterochiral phase. Even so, this lower bound is two to four times higher than the often-quoted conglomerate prevalence rate, a value that is also based on (experimental) thermodynamic quantities. In addition, our results are used to reexamine Wallachs rule and the close-packing principle. It is concluded that the prevalence of stable conglomerates has been underestimated, and, provided thermodynamic equilibrium drives the crystallization process, preferential crystallization has a much wider scope of applicability than previously assumed.
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