Selecting Resolving Agents with Respect to Their Eutectic Compositions

Szeleczky, Zsolt; Semsey, Sándor; Bagi, Péter; Pálovics, Emese; Faigl, Ferenc; Fogassy, Elemér

doi:10.1002/chir.22564

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…This could be particularly important for chiral molecules unresolvable by current industrially standard methods, such as via formation of diastereomeric salts. 39 In cases such as this, where a new route of crystallization consistently produces crystals below a standard and quality for scXRD, 3D ED has shown that it is possible to overcome these challenges. This serves as a proof-of-concept that 3D ED can form a symbiotic relationship with crystallization from a new kind of volatile deep eutectic solvent.…”

Section: Discussionmentioning

confidence: 99%

“…Formation of a conglomerate via a desolvation-like process in which the coformer spontaneously leaves the system may open up a new avenue by which to achieve racemic resolution. This could be particularly important for chiral molecules unresolvable by current industrially standard methods, such as via formation of diastereomeric salts . In cases such as this, where a new route of crystallization consistently produces crystals below the useful size for scXRD, 3D ED can successfully meet the challenge.…”

Section: Discussionmentioning

confidence: 99%

“…This could be particularly important for chiral molecules unresolvable by current industrially standard methods, such as via formation of diastereomeric salts. 39 In cases Thermogram of Form A-rac grown from a ratio of ≥4:1 (PhOH/MTX) (red) which undergoes an endothermic event at 122 °C and Form A-R/ S grown from a ratio of 3:1 which undergoes an endothermic event at 115 °C followed by a small exotherm before undergoing a second endothermic event at 122 °C (blue). All thermograms were taken at a ramp rate of 10 °C/min from heat/cool cycles between 30 and 150 °C.…”

Section: Crystal Growth and Designmentioning

confidence: 99%

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Racemic Conglomerate Formation via Crystallization of Metaxalone from Volatile Deep Eutectic Solvents

Hamilton

Andrusenko

Potticary

et al. 2020

Crystal Growth & Design

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The pharmaceutical metaxalone (MTX) was obtained as a conglomerate Form A-R/S, via a newly reported crystallization method exploiting volatile deep eutectic solvents.Homochiral crystals of Form A-S, could previously be obtained only by crystallization from enantiopure MTX, synthesized from enantiopure starting materials, and never from a racemic solution of MTX. Homochiral crystals of Form A-R were obtained here concomitantly for the first time. Powder X-ray diffraction and chiral high performance liquid chromatography were used to infer that the structure of the crystals obtained were a conglomerate relating to the known Form A-S. However, this pathway results in exclusively micron-sized needles, below typical structural solution size, and so 3D electron diffraction, combining low-dose continuous acquisition and a dedicated single-electron detector was used for ab-initio structural solution of Form A-R/S. Crystallization via volatile deep eutectic solvents allowed the structural landscape of metaxalone to be further explored, adding a point to its phase diagram. This example highlights the possibility 2 for symbiotic relationships between structural solution via electron diffraction and crystallisation pathways which do not result in crystals of a suitable size and quality for single-crystal X-ray diffraction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…This could be particularly important for chiral molecules unresolvable by current industrially standard methods, such as via formation of diastereomeric salts. 39 In cases Thermogram of Form A-rac grown from a ratio of ≥4:1 (PhOH/MTX) (red) which undergoes an endothermic event at 122 °C and Form A-R/ S grown from a ratio of 3:1 which undergoes an endothermic event at 115 °C followed by a small exotherm before undergoing a second endothermic event at 122 °C (blue). All thermograms were taken at a ramp rate of 10 °C/min from heat/cool cycles between 30 and 150 °C.…”

Section: Crystal Growth and Designmentioning

confidence: 99%

See 1 more Smart Citation

Racemic Conglomerate Formation via Crystallization of Metaxalone from Volatile Deep Eutectic Solvents

Hamilton

Andrusenko

Potticary

et al. 2020

Crystal Growth & Design

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“…Furthermore, the purified product usually requires further cycles of resolution to obtain the desirable optical purity. Consequently, besides the traditional well-known acid and amine resolving agents, the quest for new useful compounds with chiral moieties incorporated in their structures continues 40 and it is desirable to have an efficient and simple process for the resolution of racemic mixtures that is easily scalable to industrial production.…”

Section: Introductionmentioning

confidence: 99%

Resolution of Racemic Mixtures by Phase Transition of PEGylated Resolving Agents

2017

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A novel, efficient, and simple method for the resolution of racemic mixtures is presented in which PEGylated resolving agents are subjected to diastereomeric complex formation in alcohols. The resulting complexes then undergo temperature-assisted phase transition, affording a precipitate that is enriched in one enantiomer and separable by filtration. In an aqueous solution, phase transition can be caused by the methods used in the precipitation of poly(ethylene glycol) (e.g., addition of ammonium sulfate). A number of racemic amines have been successfully resolved using this method. The first cycle of resolution affords the amines with an optical purity of 72–85% from their corresponding racemic mixture in good yields (78–90%). An additional cycle improved the optical purity to 87–95%. The PEGylated resolving agents can be recovered and reutilized without the loss of resolution efficiency.

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Separation of Chiral Compounds: Enantiomeric and Diastereomeric Mixtures

Pálovics¹,

Szeleczky²,

Szolnoki³

et al. 2018

Laboratory Unit Operations and Experimental Methods in Chemical Engineering

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Despite the dramatic development of enantioselective synthesis and chromatographic separation methods, optical resolution still remains the cheapest and operationally simplest method for producing pure enantiomers on a larger scale. No extreme conditions or expensive reagents are required, and the eventually expensive resolving agents can be recovered. This chapter is based mainly on the authors' long experience in the resolution of industrially important molecules, and it presents new observations and establishments as well. Several methods for separation of chiral mixtures, enantiomeric and diastereomeric mixtures, are shown, and possibilities for predicting the efficiency of resolution based on the analysis of physico-chemical properties of the reactants are also described.

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Selecting Resolving Agents with Respect to Their Eutectic Compositions

Cited by 4 publications

References 23 publications

Racemic Conglomerate Formation via Crystallization of Metaxalone from Volatile Deep Eutectic Solvents

Racemic Conglomerate Formation via Crystallization of Metaxalone from Volatile Deep Eutectic Solvents

Resolution of Racemic Mixtures by Phase Transition of PEGylated Resolving Agents

Separation of Chiral Compounds: Enantiomeric and Diastereomeric Mixtures

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