Amino alcohol based chiral solvating agents: synthesis and applications in the NMR enantiodiscrimination of carboxylic acids

Four optically active amino alcohols were synthesized via the ring opening of (R)-N-(2,3-epoxypropyl)phthalimide with (R)-2-phenyl glycinol, (1R,2S)-cis-1-amino-2-indanol, (R)-2-amino-1-butanol and (S)-phenyl ethylamine in 73–93% yields. The enantioselective recognition of these receptors towards the enantiomers of racemic carboxylic acids was studied by 1H NMR spectroscopy. The molar ratio and the association constants of the chiral compounds with each of the enantiomers of the guests were determined by using Job plots and a non-linear least-squares fitting method, respectively. Large non-equivalent chemical shifts (up to 30.0 Hz) can be achieved in the presence of chiral amino alcohols 2 and 5. Amongst the chiral receptors used, compound 5 was found to be the best chiral shift reagent, and was effective in the determination of the enantiomeric excess of chiral carboxylic acids.

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2-[(2R)-2-Hydroxy-3-[[(1R)-2-hydroxy-1-phenyl-ethyl]amino]propyl] isoindoline-1,3-dioneC19H20N2O4[α]D25=+32 (c 0.75, CHCl3)Source of chirality: (R)-N-(2,3-epoxypropyl)-phthalimide and (R)-2-phenyl glycinolAbsolute configuration: (R,R)

2-[(2R)-2-Hydroxy-3-[[(1R,2S)-2-hydroxyindan-1-yl]amino]propyl]isoindoline-1,3-dioneC20H20N2O4[α]D25=+48.0 (c 0.5, CHCl3)Source of chirality: (R)-N-(2,3-epoxypropyl)-phthalimide and (1R,2S)-cis-1-amino-2-indanolAbsolute configuration: (R,R,S)

2-[(2R)-2-Hydroxy-3-[[(1R)-1-(hydroxymethyl)-propyl]amino]propyl] isoindoline-1,3-dioneC15H20N2O4[α]D25=-24.0 (c 0.75, CHCl3)Source of chirality: (R)-N-(2,3-epoxypropyl)-phthalimide and (R)-2-amino-1-butanolAbsolute configuration: (R,R)

2-[(2R)-2-Hydroxy-3-[[(1S)-1-phenylethyl]-amino]propyl]isoindoline-1,3-dioneC19H20N2O3[α]D25=-16.0 (c 1.0, CHCl3)Source of chirality: (R)-N-(2,3-epoxypropyl)-phthalimide and (S)-phenyl ethylamineAbsolute configuration: (R,S)