Novel NMR chiral solvating agents derived from (1R,2R)-diaminocyclohexane: synthesis and enantiodiscrimination for chiral carboxylic acids

A series of new compounds, (1R,2R)-1-(1′,8′-naphthalimide)-2-aminocyclohexane 1 and its 4′-derivatives 2 and 3 derived from (1R,2R)-1,2-diaminocyclohexane have been synthesized conveniently and efficiently. 1H NMR spectroscopy was employed to investigate their enantiodiscriminating ability. Compared with α-phenylethylamine, a commercially available chiral solvating agent (CSA), these compounds exhibited better enantiodiscriminating ability toward the chiral carboxylic acids we had chosen, distinguishing them as promising and practical CSAs.

(1R,2R)-1-(1′,8′-Naphthalimide)-2-aminocyclohexane and its 4′-derivatives derived from (1R,2R)-diaminocyclohexane are efficient NMR chiral solvating agents for chiral carboxylic acids leading to large separation (ΔΔδ up to 104.1 Hz) of the proton signals of the enantiomers.Figure optionsDownload as PowerPoint slide

(1R,2R)-1-(1′,8′-Naphthalimide)-2-aminocyclohexaneC18H18N2O2Ee 100%[α]D20=+2.3 (c 2.50, CHCl3)Source of chirality: (1R,2R)-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)

(1R,2R)-1-(4′-Bromo-1′,8′-naphthalimide)-2-aminocyclohexaneC18H17BrN2O2Ee 100%[α]D20=-12.8 (c 0.065, CHCl3)Source of chirality: (1R,2R)-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)

(1R,2R)-1-(4′-Dimethylamino-1′,8′-naphthalimide)-2-aminocyclohexaneC20H23N3O2Ee 100%[α]D20=-16.0 (c 0.025, CHCl3)Source of chirality: (1R,2R)-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)