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We here highlight the importance of stoichiometry for simultaneous cocrystal resolution. Focusing on combining the racemates of binol and proline, we show that a 1 : 2 ratio leads to formation of a full racemic compound, whereas a 2 : 1 ratio, leads to conglomerate formation, with simultaneous resolution of both binol and proline. Playing on stoichiometry, one achieves a reversible switch between the racemic compound and conglomerate. This is the first investigation of such behavior combining two racemates. [ABSTRACT FROM AUTHOR]

Temperature-Cycle-Induced Deracemization (TCID) offers a promising approach to obtain enantiopure solids from racemic mixtures. By combining rapid racemization in solution and temperature swings, homochirality is theoretically achieved. Despite theoretical expectations of doubled yields compared to traditional chiral separation methods, such as in Preferential Crystallization, experimental validation remains lacking. We applied TCID to (1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-one) (Cl-TAK), introducing a post-TCID cooling step to enhance yield and a washing step to augment enantiopurity. This refinement yielded an 89.8% mass yield with 99.1% enantiomeric excess in the crystal phase (c.e.e.) within 24 h on an 8.75 g scale, showcasing improved performance with insignificant process duration extension. Additionally, we explored the stochasticity of deracemization, observing the development from low initial crystal enantiomeric excesses (1–6% c.e.e0) at a 2.5 g scale. Kinetic analysis revealed that a 2% c.e.e0 effectively mitigates chiral flipping risks and induction time in our system. Our study underscores the potential for reduced initial c.e.e. to expedite deracemization and presents a straightforward method to optimize yield and purity, facilitating industrial application. [ABSTRACT FROM AUTHOR]

A novel concept of deracemization via periodic fluctuations of solute concentration is demonstrated. Fluctuation of concentration under isothermal conditions was induced by vacuum evaporation followed by re‐addition of solvent. Complete deracemization of a scalemic suspension of N‐(2‐methylbenzylidene)‐phenylglycine amide (NMPA) was achieved. The effects of initial enantiomeric excess, vacuum pressure, and duration of evaporation on the evolution of the solid phase enantiomeric excess and the mechanism of this strategy were studied. Pure enantiomorph NMPA could be achieved by this technique in an efficient and novel procedure. The process has advantages for compounds that have solubility with a weak temperature dependence or compounds that start to decompose at low temperature. [ABSTRACT FROM AUTHOR]

Ciprofloxacin (CIF) is a powerful synthetic antibiotic usually used for chest, skin, and bone infections when the patients have resisted other antibiotics. However, ciprofloxacin has a weakness in terms of solubility, especially in water between pH 6 and 8. Therefore, we propose the formation of novel salt forms of ciprofloxacin with oxalic acid (OXA) in order to alter and improve the solubility. Liquid assisted grinding (LAG) was used as a pre-screen for salt or co-crystal formation with nine candidates for the co-former based on known synthons. The solid-state characterization results confirmed that from these nine candidates, CIF is able to form hydrated salts only with oxalic acid (OXA). Interestingly, CIF-OXA forms hydrated salts with three different stoichiometric forms with different ratios between CIF and OXA. The appearance of hydrated salts with different stoichiometry is caused by the diversity of protonated/deprotonated forms in the OXA molecule, including OXA, OXA−, and OXA2−.The precise molecular structures of the products were confirmed by SC-XRD, which found that the three products are CIF6+OXA32−·2H2O (form A), CIF2+OXA1OXA12−·2H2O (form B), and CIF2+OXA1OXA2−·2H2O (form C). Furthermore, all product forms reveal enhanced solubility in deionized water approximately 38.5, 66.0, and 41.0 times for form A, B, and C with respect to pure CIF. [ABSTRACT FROM AUTHOR]

Preferential crystallization induced by chiral surfaces is an interesting alternative to isolate enantiopure antipodes. Herein, we take advantage of the outstanding enantiorecognition capabilities of inherently chiral oligomers to induce an enantioselective crystallization process. We exemplify this strategy with two amino acid model molecules, asparagine and glutamic acid, having a completely uncorrelated structure with respect to the template. This illustrates the versatility of the approach with potential applications in the resolution of pharmaceutical compounds. [ABSTRACT FROM AUTHOR]