4-Butyl-1-(2,3,4-tri-O-acetyl-β-l-fucopyranosyl)-1H-1,2,3-triazole

The title compound, C18H27N3O7, was synthesized by CuI-catalysed coupling of an azide with an alkyne as part of a study into the synthesis of N-glycosyl-1,2,3-triazoles. The crystal structure confirms the selective formation of the β-conformer of the pyranose N-glycoside, thus confirming the retention of stereochemistry during heterocycle formation with the N-glycosyl triazole group occupying the equatorial position at the anomeric C atom. The structure exhibits two crystallographically independent molecules (A and B) with essentially identical conformations with a weighted r.m.s. deviation of only 0.09 Å. The molecules are arranged in layers with hydrophobic and more polar sections built from the butyl triazole units on the one hand and the more polar moieties dominated by the carbohydrate units on the other. Within the polar layers, intermolecular interactions are dominated by a three-dimensional network of weak C—H⋯O hydrogen bonds with the acetyl keto O atoms as the hydrogen-bond acceptors. The triazole units interact with each other via C—H⋯N hydrogen bonds which connect the molecules into two infinite chains of molecules made up of either A molecules or B molecules that stretch parallel to each other along [100]. Between the butyl groups no directional interactions are observed.

The title compound, C 18 H 27 N 3 O 7 , was synthesized by Cu Icatalysed coupling of an azide with an alkyne as part of a study into the synthesis of N-glycosyl-1,2,3-triazoles. The crystal structure confirms the selective formation of the -conformer of the pyranose N-glycoside, thus confirming the retention of stereochemistry during heterocycle formation with the Nglycosyl triazole group occupying the equatorial position at the anomeric C atom. The structure exhibits two crystallographically independent molecules (A and B) with essentially identical conformations with a weighted r.m.s. deviation of only 0.09 Å . The molecules are arranged in layers with hydrophobic and more polar sections built from the butyl triazole units on the one hand and the more polar moieties dominated by the carbohydrate units on the other. Within the polar layers, intermolecular interactions are dominated by a three-dimensional network of weak C-HÁ Á ÁO hydrogen bonds with the acetyl keto O atoms as the hydrogen-bond acceptors. The triazole units interact with each other via C-HÁ Á ÁN hydrogen bonds which connect the molecules into two infinite chains of molecules made up of either A molecules or B molecules that stretch parallel to each other along [100]. Between the butyl groups no directional interactions are observed. Refinement R[F 2 > 2(F 2 )] = 0.046 wR(F 2 ) = 0.120 S = 1.11 5041 reflections 515 parameters 3 restraints H-atom parameters constrained Á max = 0.42 e Å À3 Á min = À0.21 e Å À3 Table 1 Hydrogen-bond geometry (Å , ). 4-Butyl-1-(2,3,4-tri-O-acetyl--L-fucopyranosyl)-1H-1,2,3-triazole A.-B. Alhassan, P. Norris and M. Zeller Comment N-Glycosidic analogs of naturally occurring carbohydrates are receiving a growing amount of attention due to their potential in medicinal chemistry (Norris, 2008;Temelkoff et al., 2006). As part of a study into the synthesis of N-glycosyl-1,2,3triazoles, the title compound was found to be the only 1,2,3-triazole product formed from the reaction of 2,3,4-tri-O-acetylβ-L-fucopyranosyl azide (Zhang et al., 2007) with 1-hexyne and catalytic CuSO 4 /ascorbic acid (Fig. 1).

Related literature
The structure exhibits two crystallographically independent molecules A and B ( Fig. 2) with essentially identical conformations as can be seen in the overlay shown in Fig. 3. The weighted r.m.s. deviation of the two molecules is only 0.09 Å.
Both molecules exhibit unexceptional chair conformations for the pyranose ring and straight all-trans chains for the butyl chains. The crystal structure reveals the β-configuration of the pyranose N-glycoside (Fig. 2). This confirms the retention of stereochemistry during heterocycle formation with the N-glycosyl triazole group occupying the equatorial position at the anomeric carbon atom. Also, the complete regioselectivity of the cycloaddition process is supported with only the 1,4-1H-1,2,3-triazole being formed as the 1 H NMR spectrum of the crude reaction mixture did not show any additional signals that may indicate the formation of the corresponding 1,5-isomer.  Table 1). In the hydrophobic layer dominated by the butyl groups no directional interactions are observed.

Experimental
The triazole was prepared from 2,3,4-tri-O-acetyl-β-L-fucosyl azide (0.4 g, 1.27 mmol), 1-hexyne (0.16 ml, 1.38 mmol), 1M CuSO 4 (0.3 ml, 0.3 mmol), 1M ascorbic acid (0.4 ml, 0.4 mmol) and 10 ml of 1:1 ethanol/H 2 O as solvent. The mixture was heated to 345.5 K (70 °C) and allowed to stir vigorously until TLC showed the completion of the reaction. The reaction was monitored by TLC (1:1, hexane-ethyl acetate, R f = 0.41). After cooling to room temperature, ice water was added to the mixture which led to the precipitation of the triazole product which was then isolated by filtration through a glass frit.

Refinement
Treatment of hydrogen atoms: All hydrogen atoms were added in calculated positions with a C-H bond distance of 0.95 Å (triazole H), 0.98 Å (methyl) or 1.00 Å (others). They were refined with isotropic displacement parameters of 1.5 times (methyl) or 1.2 times (others) that of the equivalent isotropic displacement parameter of the adjacent carbon atom. Methyl hydrogen atoms were allowed to rotate to best fit the experimental electron density.
Friedel pairs were merged prior to refinement. The absolute structure was assigned based on the known stereochemistry of carbon atoms not being changed during the synthesis of the compound.      Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.