Enantiomeric Resolution of (±)-Mandelic Acid by (1R,2S)-(–)-Ephedrine. An Organic Chemistry Laboratory Experiment Illustrating Stereoisomerism

Abstract

There has been an increasing need, particularly in the pharmaceutical industry, to prepare chiral substances in single-isomer form. A chiral technique that makes an excellent introductory organic chemistry experiment is enantiomeric resolution. The classical resolution of (±)-mandelic acid using the chiral amine, (1R,2S)-(–)-ephedrine, was adapted for use in introductory organic chemistry lab curricula. (–)-Ephedrine and (±)-mandelic acid were reacted to produce diasteromeric ephedrinemandelate salts. The [(1R,2S)-(–)-ephedrine][(R)-(–)-mandelate] preferentially precipitated, was recrystallized, and analyzed by melting point, 168–170 °C (lit. 170 °C), 52% yield. The [(–)-ephedrine-][(–)-mandelate] was neutralized with 6 M HCl, extracted and rotary evaporated to produce a white solid in 32% yield whose melting point, 132–134 °C (lit. 133–134 °C), confirmed its identity as (R)-(–)-mandelic acid with a specific rotation of -135°, which corresponds to 85% optical purity.