Discrimination in resolving systems. II: Ephedrine-substituted mandelic acids

Area of Science:

• Crystallography
• Physical Chemistry
• Organic Chemistry

Background:

• Diastereomeric salts are crucial in chiral resolution and understanding molecular interactions.
• Ephedrine and mandelic acid derivatives are commonly used chiral resolving agents.
• Solubility and crystal packing significantly impact the physical properties of organic salts.

Purpose of the Study:

• To investigate the structural and property differences of binary diastereomeric ephedrine salts with various mandelic acid derivatives.
• To correlate crystal packing, hydrogen bonding patterns, and molecular conformations with observed solubility and thermal properties.
• To elucidate the influence of mandelic acid substituents on salt formation and solid-state behavior.

Main Methods:

• Synthesis and crystallization of (-)-ephedrine salts with substituted mandelic acids from 95% ethanol.
• X-ray crystallography to determine the solid-state structures of the diastereomeric salts.
• Solubility, melting point, and heat of fusion measurements to characterize physical properties.

Main Results:

• Significant solubility differences were observed between diastereomeric salts, with distinct crystal structures.
• (2R)-mandelate salts showed more ordered structures with shorter hydrogen-bonding chains and higher melting points.
• (2S)-mandelate salts exhibited greater structural variability, influencing their physical properties and solubility trends, especially with larger substituents.

Conclusions:

• The stereochemistry of mandelic acid profoundly affects the crystal packing and hydrogen bonding in ephedrine salts.
• Structural variations directly correlate with differences in solubility, melting points, and heats of fusion.
• Substituent effects on mandelic acid can alter the trend of solubility discrimination between diastereomers.