Lipase mediated kinetic resolution of benzimidazolyl ethanols

Enantioselective trans-acylation of the racemic benzimidazolyl ethanols was achieved via enzymatic kinetic resolution. A range of commercially available lipases were screened and Novozyme-435 was established as the optimal catalyst. N-Protection was found to be mandatory for effective transesterification. However, electron-withdrawing substituents reduced the enantioselectivity to some extent when compared to the other substituents.

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(R)-1-(1H-Benzo[d]imidazol-2-yl)ethyl acetateC11H12N2O2[α]D = +59.4 (c 0.9, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (R)

(S)-1-(1H-Benzo[d]imidazol-2-yl)ethanolC9H10N2O[α]D = −13.5 (c 1.1, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (S)

(R)-1-(1-Methyl-1H-benzo[d]imidazol-2-yl)ethyl acetateC12H14N2O2[α]D = +63.6 (c 1.0, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (R)

(S)-1-(1-Methyl-1H-benzo[d]imidazol-2-yl)ethanolC10H12N2O[α]D = −8.6 (c 1.0, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (S)

1-(1-Benzoyl-1H-benzo[d]imidazol-2-yl)-(1R)-ethyl acetateC18H16N2O3[α]D = +27.8 (c 1.0, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (R)

2-[1-Hydroxy-(1S)-ethyl]-1H-benzo[d]imidazol-1-yl-phenylmethanoneC16H14N2O2[α]D = −36.0 (c 1.0, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (S)

(R)-1-(1-Tosyl-1H-benzo[d]imidazol-2-yl)ethyl acetateC18H18N2O4S[α]D = +23.4 (c 0.9, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (R)

(S)-1-(1-Tosyl-1H-benzo[d]imidazol-2-yl)ethanolC16H16N2O3S[α]D = −21.8 (c 0.8, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (S)

(R)-1-(1-Benzyl-1H-benzo[d]imidazol-2-yl)ethyl acetateC18H18N2O2[α]D = +12.2 (c 0.8, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (R)

(S)-1-(1-Benzyl-1H-benzo[d]imidazol-2-yl)ethanolC16H16N2O[α]D = −15.1 (c 0.9, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (S)

1-Benzoyl-1H-benzo[d]imidazol-2-yl(phenyl)methyl acetateC23H18N2O3[α]D = +2.5 (c 1.1, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (R)

2-Hydroxy(phenyl)methyl-1H-benzo[d]imidazol-1-yl-phenylmethanoneC21H16N2O2[α]D = −6.6 (c 1.3, CH3OH)Source of chirality: kinetic resolutionAbsolute configuration: (S)