Simultaneous Chiral Resolution of Two Racemic Compounds by Preferential Cocrystallization*
Fuli Zhou1, Oleksii Shemchuk1, Maxime D Charpentier2
1Institute of Condensed Matter and Nanosciences, Place Louis Pasteur, 1 bte L4.01.06, 1348, Louvain-La-Neuve, Belgium.
Angewandte Chemie (International Ed. in English)
|July 7, 2021
Summary
This study introduces simultaneous chiral resolution of two compounds using preferential cocrystallization. The novel method effectively separates mandelic acid and etiracetam enantiomers with high purity.
Area of Science:
- Crystallization Science
- Chiral Chemistry
- Separation Science
Background:
- Preferential crystallization is a key technique for separating enantiomers.
- Simultaneous resolution of multiple compounds remains a significant challenge in chiral chemistry.
Purpose of the Study:
- To develop a novel method for simultaneous chiral resolution of two distinct racemic compounds.
- To investigate the formation of stable cocrystals between mandelic acid and etiracetam enantiomers.
- To establish a cyclic preferential crystallization process for efficient separation.
Main Methods:
- Investigated preferential cocrystallization of RS-mandelic acid (MAN) and RS-etiracetam (ETI).
- Formed enantiospecific cocrystals (R-MAN·R-ETI and S-MAN·S-ETI).
- Developed and applied a cyclic preferential crystallization process.
Main Results:
- Achieved simultaneous chiral resolution of both mandelic acid and etiracetam.
- Obtained high enantiopurity for etiracetam (ee > 98%) and mandelic acid (ee ≈ 95%).
- Demonstrated the formation of a stable conglomerate system enabling the process.
Conclusions:
- Simultaneous preferential cocrystallization is a viable strategy for resolving multiple chiral compounds.
- The developed cyclic process offers an efficient route to high-purity enantiomers.
- This work expands the scope of preferential crystallization in chiral separations.
More Related Videos
08:51Coulomb Explosion Imaging as a Tool to Distinguish Between Stereoisomers
Published on: August 18, 2017
10.5K
06:31Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators
Published on: November 27, 2015
9.8K
Related Concept Videos
02:30Racemic Mixtures and the Resolution of Enantiomers
19.7K
A racemic mixture, or racemate, is an equimolar mixture of enantiomers of a molecule that can be separated using their unique interaction with chiral molecules or media. Racemic mixtures are denoted by the (±)- prefix. This ‘optical rotation descriptor’ applies to the whole solution of a racemic mixture rather than a specific stereoisomer. Enantiomers typically have the same physical and chemical properties. Hence, they are not easily separable. However, enantiomers can exhibit...
19.7K
02:05Prochirality
4.2K
The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...
4.2K
02:15SN1 Reaction: Stereochemistry
9.2K
This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
9.2K
01:12Stereochemical Effects of Enolization
2.2K
The chiral α-carbon of the carbonyl compound is the stereocenter of the molecule. As shown in the figure below, when such a carbonyl compound undergoes racemization under an acidic or basic condition, an achiral enol is formed.
2.2K
02:25Molecules with Multiple Chiral Centers
14.0K
Molecules that possess multiple chiral centers can afford a large number of stereoisomers. For instance, while some molecules like 2-butanol have one chiral center, defined as a tetrahedral carbon atom with four different substituents attached, several molecules like butane-2,3-diol have multiple chiral centers. A simple formula to predict the number of stereoisomers possible for a molecule with n chiral centers is 2n. However, there can be a lower number where some of the stereoisomers are...
14.0K
02:30Chirality at Nitrogen, Phosphorus, and Sulfur
6.3K
Chirality is most prevalent in carbon-based tetrahedral compounds, but this important facet of molecular symmetry extends to sp3-hybridized nitrogen, phosphorus and sulfur centers, including trivalent molecules with lone pairs. Here, the lone pair behaves as a functional group in addition to the other three substituents to form an analogous tetrahedral center that can be chiral.
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
6.3K