New Discoveries in Enantiomeric Separation of Racemic Tofisopam

Miklós Hunor Bosits, Emese Pálovics, J. Madarász, E. Fogassy

Research output: Contribution to journalArticle

Abstract

Resolution process of tofisopam has been re-evaluated now based on our new investigations. Originally, it was carried out in the water-chloroform system, where the intermediate salt of high diastereomeric excess was described as (R)-TOF·(R,R)-DBTA·(H 2 O) 3 . Opposed to previous assumptions, we have actually found that a different solvate composition, (R)-TOF-(R,R)-DBTA-CHCl 3 , forms with chloroform, in which molecules of CHCl 3 are captured and held with different strengths. Moreover, resolution of TOF with (R,R)-DBTA is possible (and favourable) in water-free solvent and solvent mixture. However, presence of chloroform is essential, and thus, chloroform is also a suitable solvent alone. Among the tested solvents, toluene-chloroform mixture results in the highest resolution efficiency, while the highest enantiomeric purity was achieved when acetonitrile was in the system too. Resolution efficiency can be also increased by using the quasi-racemic resolving agent and thermodynamic control. Purification of enantiomeric mixtures was examined, and recrystallization of the diastereomeric salt was found to be the most efficient solution. Instructive behaviour of the complex enantiomer-conformer system of tofisopam is emphasized.

Original languageEnglish
Article number4980792
JournalJournal of Chemistry
Volume2019
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Chloroform
Salts
Enantiomers
Water
Toluene
Purification
Crystallization
tofisopam
Thermodynamics
Molecules
Chemical analysis

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

New Discoveries in Enantiomeric Separation of Racemic Tofisopam. / Bosits, Miklós Hunor; Pálovics, Emese; Madarász, J.; Fogassy, E.

In: Journal of Chemistry, Vol. 2019, 4980792, 01.01.2019.

Research output: Contribution to journalArticle

@article{4b239086e2e540e3a9f211b6418e644a,
title = "New Discoveries in Enantiomeric Separation of Racemic Tofisopam",
abstract = "Resolution process of tofisopam has been re-evaluated now based on our new investigations. Originally, it was carried out in the water-chloroform system, where the intermediate salt of high diastereomeric excess was described as (R)-TOF·(R,R)-DBTA·(H 2 O) 3 . Opposed to previous assumptions, we have actually found that a different solvate composition, (R)-TOF-(R,R)-DBTA-CHCl 3 , forms with chloroform, in which molecules of CHCl 3 are captured and held with different strengths. Moreover, resolution of TOF with (R,R)-DBTA is possible (and favourable) in water-free solvent and solvent mixture. However, presence of chloroform is essential, and thus, chloroform is also a suitable solvent alone. Among the tested solvents, toluene-chloroform mixture results in the highest resolution efficiency, while the highest enantiomeric purity was achieved when acetonitrile was in the system too. Resolution efficiency can be also increased by using the quasi-racemic resolving agent and thermodynamic control. Purification of enantiomeric mixtures was examined, and recrystallization of the diastereomeric salt was found to be the most efficient solution. Instructive behaviour of the complex enantiomer-conformer system of tofisopam is emphasized.",
author = "Bosits, {Mikl{\'o}s Hunor} and Emese P{\'a}lovics and J. Madar{\'a}sz and E. Fogassy",
year = "2019",
month = "1",
day = "1",
doi = "10.1155/2019/4980792",
language = "English",
volume = "2019",
journal = "E-Journal of Chemistry",
issn = "2090-9063",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - New Discoveries in Enantiomeric Separation of Racemic Tofisopam

AU - Bosits, Miklós Hunor

AU - Pálovics, Emese

AU - Madarász, J.

AU - Fogassy, E.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Resolution process of tofisopam has been re-evaluated now based on our new investigations. Originally, it was carried out in the water-chloroform system, where the intermediate salt of high diastereomeric excess was described as (R)-TOF·(R,R)-DBTA·(H 2 O) 3 . Opposed to previous assumptions, we have actually found that a different solvate composition, (R)-TOF-(R,R)-DBTA-CHCl 3 , forms with chloroform, in which molecules of CHCl 3 are captured and held with different strengths. Moreover, resolution of TOF with (R,R)-DBTA is possible (and favourable) in water-free solvent and solvent mixture. However, presence of chloroform is essential, and thus, chloroform is also a suitable solvent alone. Among the tested solvents, toluene-chloroform mixture results in the highest resolution efficiency, while the highest enantiomeric purity was achieved when acetonitrile was in the system too. Resolution efficiency can be also increased by using the quasi-racemic resolving agent and thermodynamic control. Purification of enantiomeric mixtures was examined, and recrystallization of the diastereomeric salt was found to be the most efficient solution. Instructive behaviour of the complex enantiomer-conformer system of tofisopam is emphasized.

AB - Resolution process of tofisopam has been re-evaluated now based on our new investigations. Originally, it was carried out in the water-chloroform system, where the intermediate salt of high diastereomeric excess was described as (R)-TOF·(R,R)-DBTA·(H 2 O) 3 . Opposed to previous assumptions, we have actually found that a different solvate composition, (R)-TOF-(R,R)-DBTA-CHCl 3 , forms with chloroform, in which molecules of CHCl 3 are captured and held with different strengths. Moreover, resolution of TOF with (R,R)-DBTA is possible (and favourable) in water-free solvent and solvent mixture. However, presence of chloroform is essential, and thus, chloroform is also a suitable solvent alone. Among the tested solvents, toluene-chloroform mixture results in the highest resolution efficiency, while the highest enantiomeric purity was achieved when acetonitrile was in the system too. Resolution efficiency can be also increased by using the quasi-racemic resolving agent and thermodynamic control. Purification of enantiomeric mixtures was examined, and recrystallization of the diastereomeric salt was found to be the most efficient solution. Instructive behaviour of the complex enantiomer-conformer system of tofisopam is emphasized.

UR - http://www.scopus.com/inward/record.url?scp=85065603410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065603410&partnerID=8YFLogxK

U2 - 10.1155/2019/4980792

DO - 10.1155/2019/4980792

M3 - Article

AN - SCOPUS:85065603410

VL - 2019

JO - E-Journal of Chemistry

JF - E-Journal of Chemistry

SN - 2090-9063

M1 - 4980792

ER -