NMR Studies Of Drugs. Chiral Solvating Agents for Direct Determination of Enantiomeric Excess of the Cardiac Antiarrhythmic, Mexiletine

Abstract

The 400 MHz ¹H NMR spectra of the cardiac antiarrhythmic, mexiletine, 1, have been studied with different chiral solvating agents (CSA) to obtain a very promising method for direct determination of enantiomeric excess (e.e.) with limited amounts of 1. The methods included the use of β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA), and 2,2,2-trifluoro-1-(9-anthryl)ethanol (TFAE). Use of TFAE in CDCl₃ with the free base of 1 appeared to give the best results, with enantiomeric shift differences observed for the signals of the sidechain methyl, CH ₃CH, and the aryl methyls.

Key Words:

• Optical Purity
• Enantiomer
• Analysis
• 1-(2,6-Dimethylphenoxy)-2-propanamine
• Antiarrhythmic
• Cyclodextrin
• α-Methoxy-α-(trifluoromethyl)phenylacetic acid
• MTPA
• 2,2,2-Trifluoro-1-(9-anthryl)ethanol
• TFAE