Optically active imidazole N-oxides derived from l-prolinamine1

Starting with (S)-1-benzylprolinamine and α-hydroxyimino ketones, enantiomerically pure bisheterocyclic imidazole N-oxides bearing the (S)-configured N-benzyl(pyrrolidin-2-yl)methyl residue were prepared. These N-oxides reacted with 2,2,4,4-tetramethylcyclobutane-1,3-dithione to give the corresponding optically active imidazole-2-thione derivatives via a sulfur transfer reaction. Reduction of the N-oxides with Raney-nickel led to deoxygenation, whereas catalytic hydrogenation (Pd/C) in ethanol occurred with simultaneous deoxygenation and debenzylation, leading to optically active 1-(pyrrolidin-2-yl)methyl-1H-imidazoles. Alkylation of the prepared imidazole N-oxides and their respective imidazoles with butyl and hexyl bromide and subsequent anion exchange gave optically active N-alkoxy- and N-alkylimidazolium tetrafluoroborates, respectively, with the properties of ‘room temperature ionic liquids’.

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1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4,5-dimethyl-1H-imidazole 3-oxideC17H24N3OEe = 100%[α]D25=-18 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4-methyl-5-phenyl-1H-imidazole 3-oxideC22H26N3OEe = 100%[α]D25=-24 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4,5-diphenyl-1H-imidazole 3-oxideC27H28N3OEe = 100%[α]D25=-5 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

N-Phenyl-1-{[(2S)-N-benzylpyrrolidin-2-yl]methyl}-5-methyl-1H-imidazole-4-carboxamide 3-oxideC23H27N4O2Ee = 100%[α]D25=-27 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

N-(4-Bromophenyl)-1-{[(2S)-N-benzylpyrrolidin-2-yl]methyl}-5-methyl-1H-imidazole-4-carboxamide 3-oxideC23H26BrN4O2Ee = 100%[α]D25=-22 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4,5-dimethyl-1H-imidazoleC17H24N3Ee = 100%[α]D25=-25 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4-methyl-5-phenyl-1H-imidazoleC22H26N3Ee = 100%[α]D25=-25 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

4,5-Diphenyl-1-{[(2S)-N-benzylpyrrolidin-2-yl]methyl}-1H-imidazoleC27H28N3Ee = 100%[α]D25=-31 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

N-Phenyl-1-{[(2S)-N-benzylpyrrolidin-2-yl]methyl}-5-methyl-1H-imidazole-4-carboxamideC23H27N4OEe = 100%[α]D25=-11 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

N-(4-Bromophenyl)-1-{[(2S)-N-benzylpyrrolidin-2-yl]methyl}-5-methyl-1H-imidazole-4-carboxamideC23H26BrN4OEe = 100%[α]D25=-10 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

4,5-Diphenyl-1-[(2S)-pyrrolidin-2-yl]methyl-1H-imidazoleC21H22N3Ee = 100%[α]D25=-18 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

5-Methyl-N-phenyl-1-[(2S)-pyrrolidin-2-yl]methyl-1H-imidazole-4-carboxamideC22H23N4OEe = 100%[α]D25=-24 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4,5-dimethyl-1,3-dihydro-2H-imidazole-2-thioneC17H24N3SEe = 100%[α]D25=-19 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4,5-diphenyl-1,3-dihydro-2H-imidazole-2-thioneC27H28N3SEe = 100%[α]D25=-14 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

N-(4-Bromophenyl)-1-{[(2S)-N-benzylpyrrolidin-2-yl]methyl}-5-methyl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxamideC23H26BrN4OSEe = 100%[α]D25=-10 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-3-hexyl-4,5-dimethyl-1H-imidazolium tetrafluoroborateC23H36BF4N3Ee = 100%[α]D25=-35 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylopyrrolidin-2-yl]methyl}-4,5-dimethyl-3-octyl-1H-imidazolium tetrafluoroborateC25H40BF4N3Ee = 100%[α]D25=-22 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-3-butyl-4-methyl-5-phenyl-1H-imidazolium tetrafluoroborateC26H34BF4N3Ee = 100%[α]D25=-10 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4-methyl-3-octyl-5-phenyl-1H-imidazolium tetrafluoroborateC30H42BF4N3Ee = 100%[α]D25=-27 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-3-butoxy-4,5-dimethyl-1H-imidazolium tetrafluoroborateC21H32BF4N3OEe = 100%[α]D25=-33 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-4,5-dimethyl-3-octyloxy-1H-imidazolium tetrafluoroborateC21H40BF4N3OEe = 100%[α]D25=-26 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-3-butoxy-4-methyl-5-phenyl-1H-imidazolium tetrafluoroborateC26H34BF4N3OEe = 100%[α]D25=-25 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-3-hexyloxy-4-methyl-5-phenyl-1H-imidazolium tetrafluoroborateC28H38BF4N3OEe = 100%[α]D25=-17 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

1-{[(2S)-N-Benzylpyrrolidin-2-yl]methyl}-3-butoxy-4,5-diphenyl-1H-imidazolium tetrafluoroborateC31H36BF4N3OEe = 100%[α]D25=-16 (c 1.00, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)