Resolution via diastereomeric amides of enantiopure 1,4-benzoxathian-2- and 3-carboxylic acids and determination of their configuration

Chirality. 2022 Aug;34(8):1053-1064. doi: 10.1002/chir.23474. Epub 2022 May 20.


1,4-Benzoxathiane, 2- or 3-substituted, is an important scaffold, and despite its presence in several therapeutic agents, it is chemically unexploited. Furthermore, only a few examples in literature report this moiety in its enantiopure form. Here, taking advantage to the formation of diastereomeric amides by using (S)-phenylethylamine, which show significant differences in terms of 1 H-nuclear magnetic resonance (NMR) spectra and other physical chemical properties, we defined for the first time the absolute configuration of each amide, both 2- or 3-substituted. Moreover, the diastereomeric amides were further hydrolyzed in acid conditions, letting to the achievement of the corresponding 1,4-benzoxathian carboxylic acids.

Keywords: (S)-phenylethylamine; 1,4-benzoxathiane-2-carboxamide; 1,4-benzoxathiane-3-carboxamide; 1H NMR comparison; absolute configuration determination; chiral HPLC; diastereomeric amides.

MeSH terms

  • Amides* / chemistry
  • Carboxylic Acids* / chemistry
  • Magnetic Resonance Spectroscopy
  • Phenethylamines
  • Stereoisomerism


  • Amides
  • Carboxylic Acids
  • Phenethylamines