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Reliable Mechanochemistry: Protocols for Reproducible Outcomes of Neat and Liquid Assisted Ball-mill Grinding Experiments
Published on: January 23, 2018
Solid state grinding as a tool to aid enantiomeric resolution by cocrystallisation.
Mark D Eddleston1, Mihails Arhangelskis, Tomislav Friščić
1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Chemical Communications (Cambridge, England)
|October 18, 2012
Summary
Racemic malic acid was transformed into two unique diastereomeric cocrystal phases. This was achieved by grinding with a single enantiomer of tartaric acid using liquid-assisted grinding.
Area of Science:
- Solid-state chemistry
- Crystallography
- Supramolecular chemistry
Background:
- Cocrystal formation is a key strategy in pharmaceutical development for modifying drug properties.
- Malic acid and tartaric acid are organic acids with chiral centers, offering potential for stereoselective cocrystallization.
Purpose of the Study:
- To investigate the formation of diastereomeric cocrystals between malic acid and tartaric acid.
- To explore the use of liquid-assisted grinding for solid-state synthesis of chiral cocrystals.
Main Methods:
- Liquid-assisted grinding (LAG) was employed as the primary solid-state synthesis technique.
- Characterization of the resulting solid phases was performed using techniques suitable for cocrystal analysis.
Main Results:
- The study successfully demonstrated the formation of diastereomeric cocrystals of malic acid and tartaric acid.
- Racemic malic acid was converted into two distinct diastereomeric cocrystal phases through grinding with a single enantiomer of tartaric acid.
Conclusions:
- Liquid-assisted grinding is an effective method for producing specific diastereomeric cocrystals.
- Stereoselective cocrystal formation is achievable between malic acid and tartaric acid, yielding distinct solid phases.
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