Exploring the Crystal Landscape of Mandelamide and Chiral Resolution via Cocrystallization

Area of Science:

• Crystallography
• Chiral Chemistry
• Organic Synthesis

Background:

• Mandelamide exists as enantiomers, R and S forms.
• Chiral resolution is crucial for separating enantiomers in pharmaceuticals and fine chemicals.
• Cocrystallization is a potential method for chiral resolution.

Purpose of the Study:

• To determine the crystal structures of racemic, S-enantiomer, and enantioenriched mandelamide.
• To synthesize and characterize diastereomeric cocrystals of S-mandelamide with mandelic acid and proline enantiomers.
• To investigate the potential of these diastereomeric cocrystals for chiral resolution.

Main Methods:

• X-ray crystallography for crystal structure determination.
• Cocrystal synthesis via solution crystallization.
• Stoichiometric analysis of synthesized cocrystals.

Main Results:

• Crystal structures of (±)-mandelamide, S-mandelamide, and 94% S-enantioenriched mandelamide were determined.
• 1:1 diastereomeric cocrystals of S-mandelamide with S-mandelic acid and R-mandelic acid were formed.
• Diastereomeric cocrystals of S-mandelamide with proline exhibited varying stoichiometries.
• Preliminary studies indicated the potential of this system for chiral resolution.

Conclusions:

• The crystal structures provide insights into the solid-state behavior of mandelamide enantiomers.
• Diastereomeric cocrystallization with mandelic acid and proline offers a viable strategy for chiral resolution of mandelamide.
• Further investigation is warranted to optimize this cocrystallization approach for efficient enantiomeric separation.