Study of aryl triazoles for absolute configuration determination

A variety of chiral mono- and di-1,4-disubstituted 1,2,3-triazoles were synthesized by CuAAC ‘click chemistry’ as model compounds and their spectroscopic properties characterized. The UV and CD studies of these compounds showed that 4-substituted aryl triazoles give rise to moderate exciton CD curves, under either homo- or hetero-coupling. The direction of the electric transition moment of the non-symmetric chromophores was determined by conformational analysis and supported by NMR data. The signs of the Cotton effects of the CD spectra were in complete agreement with the determined directions of the electric transition moments of the chromophores. Therefore, 4-substituted aryl triazoles can be used for the determination of the absolute configuration of organic compounds. In addition, the 4-(4-bromophenyl)-1,2,3-triazole allows for red-shifted chromophores to be obtained via Suzuki reactions, thus avoiding overlap with the substrate absorptions.

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2,3,4,6-Tetra-O-acetyl-1-(4-butyl-1H-1,2,3-triazol-1-yl)-1-deoxy-β-d-glucopyranosideC20H29N3O9[α]D20 = −19.0 (c 2.1, CHCl3)CD (CH3CN) λext (Δε): 220 (−1.1), 295 nm (+0.2)Source of chirality: 1,2,3,4,6-penta-O-acetyl α-d-glucopyranose

2,3,4,6-Tetra-O-acetyl-1-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-1-deoxy-β-d-glucopyranosideC22H24BrN3O9[α]D20 = −54.0 (c 1.9, CHCl3)CD (CH3CN) λext (Δε): 247 (−4.3), 290 nm (+0.6)Source of chirality: 1,2,3,4,6-penta-O-acetyl α-d-glucopyranose

2,3,4,6-Tetra-O-acetyl-1-(4-butyl-1H-1,2,3-triazol-1-yl)-1-deoxy-α-d-glucopyranosideC20H29N3O9[α]D20 = +105.8 (c 0.1, CHCl3)CD (CH3CN) λext (Δε): br 217 (−0.5), 290 nm (+0.1)Source of chirality: 1,2,3,4,6-penta-O-acetyl α-d-glucopyranose

2,3,4,6-Tetra-O-acetyl-1-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-1-deoxy-α-d-glucopyranosideC22H24BrN3O9[α]D20 = +114.7 (c 0.1, CHCl3)CD (CH3CN) λext (Δε): 252 (+2.9), 286 nm (+0.9)Source of chirality: 1,2,3,4,6-penta-O-acetyl α-d-glucopyranose

2,3,4,6-Tetra-O-acetyl-1-deoxy-1-[4-(6-methoxy-2-naphthyl)-1H-1,2,3-triazol-1-yl]-α-d-glucopyranosideC27H29N3O10[α]D20 = +121.6 (c 0.1, CHCl3)CD (CH3CN) λext (Δε): 245 (+3.3), 253 (+4.1), 290 nm (+2.7)Source of chirality: 1,2,3,4,6-penta-O-acetyl α-d-glucopyranose

1-(4-Butyl-1H-1,2,3-triazol-1-yl)-1-deoxy-β-glucopyranosideC12H21N3O5[α]D20 = −9.0 (c 3.0, MeOH)CD (CH3OH) λext (Δε): 213 nm (−1.2)Source of chirality: 1,2,3,4,6-penta-O-acetyl α-d-glucopyranose

2,3,4,6-Tetra-O-acetyl-1-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-1-deoxy-β-d-mannopyranosideC22H24BrN3O9[α]D20 = +6.1 (c 0.5, CHCl3)CD (CH3CN) λext (Δε): 252 (+2.2), 212 nm (−2.6)Source of chirality: 1,2,3,4,6-penta-O-acetyl α-d-mannopyranose

3,4,6-Tri-O-acetyl-1,2-bis-(4-butyl-1H-1,2,3-triazol-1-yl)-1,2-dideoxy-β-d-glucopyranosideC24H36N6O7[α]D20 = +7.6 (c 0.2, CHCl3)CD (CH3CN) λext (Δε): 212 (+2.0), 228 (−1.9), 292 nm (+0.2)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-dideoxy-1,2-bis-(4-methoxycarbonyl-1H-1,2,3-triazol-1-yl)-β-d-glucopyranosideC20H24N6O11[α]D20 = +22.2 (c 0.2, CHCl3)CD (CH3CN) λext (Δε): 216 (−4.0), 290 nm (+0.5)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-dideoxy-1,2-bis-[4-(4-methylphenyl)-1H-1,2,3-triazol-1-yl]-1,2-dideoxy-β-d-glucopyranosideC30H32N6O7[α]D20 = +36.3 (c 0.2, CHCl3)CD (CH3CN) λext (Δε): 235 (+2.8), 257 (−8.3), 298 nm (+1.2)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-bis-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-1,2-dideoxy-β-d-glucopyranosideC28H26Br2N6O7[α]D20 = −99.1 (c 0.2, DMSO)CD (CH3CN) λext (Δε): 239 (+3.5), 262 (−11.3), 296 nm (+1.2)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-dideoxy-1,2-bis-[4-(methoxy-2-naphthyl)-1H-1,2,3-triazol-1-yl]-β-d-glucopyranosideC38H36N6O9[α]D20 = −191.2 (c 0.2, DMSO)CD (CH3CN) λext (Δε): 238 (+16.7), 255 nm (−29.3)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-bis-(4-butyl-1H-1,2,3-triazol-1-yl)-1,2-dideoxy-α-d-glucopyranosideC24H36N6O7[α]D20 = +141.5 (c 0.4, CHCl3)CD (CH3CN) λext (Δε): 225 (+4.5), 292 nm (+0.2)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-dideoxy-1,2-bis-(4-methoxycarbonyl-1H-1,2,3-triazol-1-yl)-α-d-glucopyranosideC20H24N6O11[α]D20 = +103.1 (c 0.2, CHCl3)CD (CH3CN) λext (Δε): 211 (+4.2), 226 (−1.4), 292 nm (+0.5)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-dideoxy-1,2-bis-[4-(4-methylphenyl)-1H-1,2,3-triazol-1-yl]-α-d-glucopyranosideC30H32N6O7[α]D20 = +77.6 (c 0.6, CHCl3)CD (CH3CN) λext (Δε): 236 (+6.2), 255 (−11.2), 296 nm (+1.1)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-bis-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-1,2-dideoxy-α-d-glucopyranosideC28H26Br2N6O7[α]D20 = +90.5 (c 0.2, DMSO)CD (CH3CN) λext (Δε): 241 (+9.3), 260 (−14.5), 293 nm (+2.0)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1,2-dideoxy-1,2-bis-[4-(methoxy-2-naphthyl)-1H-1,2,3-triazol-1-yl]-α-d-glucopyranosideC38H36N6O9[α]D20 = +101.1 (c 0.1, DMSO)CD (CH3CN) λext (Δε): 234 (+53.8), 255 nm (−69.3)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

1,2-Bis-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-1,2-dideoxy-β-d-glucopyranosideC22H20Br2N6O4[α]D20 = −124.2 (c 0.4, DMSO)CD (CH3CN) λext (Δε): 242 (+4.7), 263 (−18.1), 297 nm (+1.7)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

1,2-Bis-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-1,2-dideoxy-α-d-glucopyranosideC22H20Br2N6O4[α]D20 = +28.0 (c 0.7, DMSO)CD (CH3CN) λext (Δε): 242 (+8.9), 261 (−26.5), 299 nm (+1.1)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

(1R,2R)-1,2-Bis(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)-cyclohexaneC22H20Br2N6[α]D20 = −225.7 (c 0.2, CHCl3)CD (CH3CN) λext (Δε): 263 (−20.9), 241 nm (+4.1)Source of chirality: (1R,2R)-(−)-1,2-diaminocyclohexane

(1R,2R)-1,2-Bis(4-(biphenyl-4-ol)-1,2,3-triazol-1-yl)-cyclohexaneC34H30N6O2[α]D20 = −241.1 (c 0.1, DMSO)CD (CH3CN) λext (Δε): 298 (−19.9), 228 nm (−6.8)Source of chirality: (1R,2R)-(−)-1,2-diaminocyclohexane

3,4,6-Tri-O-acetyl-2-azido-1-O-(4-bromobenzoyl)-2-deoxy-β-d-glucopyranosideC19H20BrN3O9[α]D20 = −51.8 (c 0.2, CHCl3)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-2-azido-1-O-(4-bromobenzoyl)-2-deoxy-α-d-glucopyranosideC19H20BrN3O9[α]D20 = +111.9 (c 0.2, CHCl3)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1-O-(4-bromobenzoyl)-2-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-2-deoxy-α-d-glucopyranosideC27H25Br2N3O9[α]D20 = −53.7 (c 0.1, CHCl3)CD (CH3CN) λext (Δε): 258 (−21.5), 240 nm (+12.0)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride

3,4,6-Tri-O-acetyl-1-O-(4-bromobenzoyl)-2-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-2-deoxy-α-d-glucopyranosideC27H25Br2N3O9[α]D20 = +169.0 (c 0.1, CHCl3)CD (CH3CN) λext (Δε): 258 (+30.9), 239 nm (−11.4)Source of chirality: 2-amino-2-deoxy-d-glucose hydrochloride