New Discoveries in Enantiomeric Separation of Racemic Tofisopam

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·(H2O)3. Opposed to previous assumptions, we have act...

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Main Authors: Miklós Hunor Bosits, Emese Pálovics, János Madarász, Elemér Fogassy
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Chemistry
Online Access:http://dx.doi.org/10.1155/2019/4980792
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author Miklós Hunor Bosits
Emese Pálovics
János Madarász
Elemér Fogassy
author_facet Miklós Hunor Bosits
Emese Pálovics
János Madarász
Elemér Fogassy
author_sort Miklós Hunor Bosits
collection DOAJ
description 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·(H2O)3. Opposed to previous assumptions, we have actually found that a different solvate composition, (R)-TOF‐(R,R)-DBTA-CHCl3, forms with chloroform, in which molecules of CHCl3 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.
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spelling doaj-art-ead6aad081c946a9b56aeef14225bf722025-02-03T01:10:16ZengWileyJournal of Chemistry2090-90632090-90712019-01-01201910.1155/2019/49807924980792New Discoveries in Enantiomeric Separation of Racemic TofisopamMiklós Hunor Bosits0Emese Pálovics1János Madarász2Elemér Fogassy3Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, 1111 Budafoki út 8, Budapest, HungaryBudapest University of Technology and Economics, Department of Organic Chemistry and Technology, 1111 Budafoki út 8, Budapest, HungaryBudapest University of Technology and Economics, Department of Inorganic and Analytical Chemistry, 1111 Szent Gellért tér 4, Budapest, HungaryBudapest University of Technology and Economics, Department of Organic Chemistry and Technology, 1111 Budafoki út 8, Budapest, HungaryResolution 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·(H2O)3. Opposed to previous assumptions, we have actually found that a different solvate composition, (R)-TOF‐(R,R)-DBTA-CHCl3, forms with chloroform, in which molecules of CHCl3 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.http://dx.doi.org/10.1155/2019/4980792
spellingShingle Miklós Hunor Bosits
Emese Pálovics
János Madarász
Elemér Fogassy
New Discoveries in Enantiomeric Separation of Racemic Tofisopam
Journal of Chemistry
title New Discoveries in Enantiomeric Separation of Racemic Tofisopam
title_full New Discoveries in Enantiomeric Separation of Racemic Tofisopam
title_fullStr New Discoveries in Enantiomeric Separation of Racemic Tofisopam
title_full_unstemmed New Discoveries in Enantiomeric Separation of Racemic Tofisopam
title_short New Discoveries in Enantiomeric Separation of Racemic Tofisopam
title_sort new discoveries in enantiomeric separation of racemic tofisopam
url http://dx.doi.org/10.1155/2019/4980792
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AT janosmadarasz newdiscoveriesinenantiomericseparationofracemictofisopam
AT elemerfogassy newdiscoveriesinenantiomericseparationofracemictofisopam