Chiral separation of beta-blockers after derivatization with (-)-alphamethoxy-alpha-(trifluoromethyl)phenylacetyl chloride by gas chromatography

Arch Pharm Res. 2001 Oct;24(5):402-6. doi: 10.1007/BF02975183.

Abstract

Gas chromatographic method was investigated for the chiral separation of several beta-blockers(atenolol, betaxolol, bisoprolol, metoprolol and pindolol) using (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent for amino group. Prior to N-acylation, hydroxyl group was converted into O-silyl ethers by react with N-methyl-N-(trimethylsilyl)trifluoroacetamide. The reaction was selective and rapid and the diastereomeric derivatives were well separated by capillary gas chromatography. (R)-isomers were eluted faster than (S)-isomers when (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride was used as the chiral derivatizing agent. But in the opposite sequence when (+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride was used. No racemization was found during the reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / isolation & purification*
  • Chromatography, Gas
  • Indicators and Reagents
  • Mass Spectrometry
  • Phenylacetates / chemical synthesis*
  • Phenylacetates / pharmacology*
  • Stereoisomerism

Substances

  • Adrenergic beta-Antagonists
  • Indicators and Reagents
  • Phenylacetates
  • alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride