Case Study on the Effects of Molecular Structure on the Mode of Polymorphic Transition Inducing Preferential Enrichment

Abstract

A series of (±)‐N‐{2‐[4‐(2‐hydroxy‐3‐ethoxypropoxy)phenylcarbamoyl]ethyl}‐N‐methylpyrrolidinium p‐halobenzenesulfonates [(±)‐1a–c] were found to cause an unusual symmetry‐breaking enantiomeric resolution phenomenon called preferential enrichment, whereas the N‐methylpiperidinium analogues (±)‐N‐{2‐[4‐(2‐hydroxy‐3‐ethoxypropoxy)phenylcarbamoyl]ethyl}‐N‐methylpiperidinium p‐halobenzenesulfonates [(±)‐2a–c] failed to show this phenomenon. By X‐ray crystallographic and ATR‐FTIR spectroscopic studies, (±)‐1a–c were found to undergo the desired solvent‐assisted solid‐to‐solid polymorphic transition of the first‐formed and metastable γ‐form into the stable δ‐form, which could induce preferential enrichment. In contrast, (±)‐2a–c were subject to the undesired solvent‐mediated polymorphic transition of the γ‐form into the α2‐form, and similarly, (±)‐1d and (±)‐2d bearing a p‐toluenesulfonate ion also showed the undesired solvent‐mediated polymorphic transition of the γ‐form into the β‐form; in these cases, preferential enrichment was not observed. Accordingly, the structure of the cyclic ammonium group as well as the basicity of the p‐substituted benzenesulfonate ion largely affected the mode of the polymorphic transition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Role of the Substituent Effect over the Squarate Oxocarbonic Ring: Spectroscopy, Crystal Structure, and Density Functional Theory Calculations of 1,2-Dianilinosquairane

“…Recently, several investigations have shown the importance of the CH-π interactions in the crystal structure, including selective enantiomeric enrichment, [34][35][36][37] properties of coordination complexes, [38][39][40][41] and mainly the folding and properties of molecular biological systems. [42][43][44][45] This weak electrostatic interaction can be seen in the ACSQ structure and also can be contributing to the hydrogen bonds for the torsion between the squarate and phenyl ring.…”

Control of polymorphic transition inducing preferential enrichment

“…In case of the -form, both crystal structures of a metastable form (-form) and the stable form (-form) were solved by X-ray crystallographic analysis and by the direct-space approach employing the Monte Carlo method with the subsequent Rietveld refinement from the powder X-ray diffraction data, respectively, permitting us to suggest the mechanism of a solid-to-solid polymorphic transition occurring during crystallization. 48 Among these four crystal forms, the -form and  1 -form were most commonly found for the compounds showing preferential enrichment, [46][47][48][49][50][51][57][58][59][60][61][62][63][64][65][66][67][68][69][70] while only one case was observed for each of the -form and -form. 45,47,48,64 Accordingly, described below is the mode of polymorphic transition of a -form polymorph into a -form or  1 -form polymorph as well as their unique crystal structures ( Figure 6).…”

Chiral Symmetry Breaking Phenomenon Caused by a Phase Transition

“…Thus far, we have found four types of solvent-assisted solid-to-solid transformations of a kinetically formed metastable γ-form crystalline phase into a thermodynamically more stable one (α-, α 1 -, δ-, or ε-form) [5,6,[20][21][22][23][24][25][33][34][35][36][37][38][39][40][41][42][43][44][45], which are relevant to the occurrence of preferential enrichment, in a process of crystal growth.…”

“…Among them, the δ-form and α 1 -form crystals are most commonly found for the compounds showing preferential enrichment [20][21][22][23][24][25][33][34][35][36][37][38][39][40][41][42][43][44][45], while only one case is observed for each of the α-and ε-forms [5,6,21,22,39]. In this section, the crystal structures of the δ-and α 1 -forms are described in detail, because this crystal structure provides a crucial information on the mechanism of the polymorphic transition causing preferential enrichment.…”