Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine via diastereomeric salt formation

Chirality. 2011 Apr;23(4):326-32. doi: 10.1002/chir.20922. Epub 2010 Nov 12.

Abstract

Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine 1 by N-(p-toluenesulfonyl)-(S)-phenylalanine 2 via diastereomeric salt formation was studied. (S)-1·(S)-2 was preferentially crystallized as a less-soluble salt from aqueous alcohol, while (R)-1·(S)-2 salt was mainly obtained by addition of solvents with a six-membered ring such as dioxane, cyclohexane, tetrahydropyran, and cyclohexene to 2-propanol. Further investigations were carried out from the viewpoints of molecular structures, optical rotation measurement, and X-ray crystallographic analyses. Crystallographic analyses have revealed that incorporation of the six-membered ring solvent molecule in (R)-1·(S)-2 without hydrogen bonds changed the molecular conformation of (S)-2 to stabilize the salt, which changed the selectivity of 1 in the enantioseparation.

MeSH terms

  • 2-Propanol / chemistry
  • Amino Acids / chemistry
  • Crystallography, X-Ray / methods*
  • Cyclohexanes / chemistry
  • Cyclohexenes / chemistry
  • Dioxanes / chemistry
  • Glycine / analogs & derivatives*
  • Glycine / chemistry
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Optical Rotation
  • Phenethylamines / chemical synthesis
  • Phenethylamines / chemistry*
  • Phenethylamines / isolation & purification*
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / chemistry
  • Salts / chemistry
  • Solvents / chemistry*
  • Stereoisomerism
  • Water / chemistry

Substances

  • Amino Acids
  • Cyclohexanes
  • Cyclohexenes
  • Dioxanes
  • N-(p-toluenesulfonyl)-(R)-phenylglycine
  • N-(p-toluenesulfonyl)-(S)-phenylalanine
  • N-benzenesulfonyl-(S)-phenylalanine
  • Phenethylamines
  • Salts
  • Solvents
  • Water
  • cyclohexene
  • Phenylalanine
  • Cyclohexane
  • 1,4-dioxane
  • 2-Propanol
  • Glycine