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

Abdul-Basit Alhassan; Peter Norris; Matthias Zeller

doi:10.1107/S1600536809028700

. 2009 Jul 25;65(Pt 8):o1992–o1993. doi: 10.1107/S1600536809028700

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

Abdul-Basit Alhassan ^a, Peter Norris ^a, Matthias Zeller ^a,^*

PMCID: PMC2977263 PMID: 21583666

Abstract

The title compound, C₁₈H₂₇N₃O₇, was synthesized by Cu^I-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.

Related literature

For background information on N-glycosidic mimics of naturally occurring carbohydrates, see: Norris (2008 ▶); Temelkoff et al. (2006 ▶). For details of the synthesis of the carbohydrate starting material used, see: Zhang et al. (2007 ▶).

Experimental

Crystal data

C₁₈H₂₇N₃O₇
M _r = 397.43
Triclinic,
a = 5.5173 (3) Å
b = 7.7442 (4) Å
c = 24.1013 (13) Å
α = 94.507 (1)°
β = 96.151 (1)°
γ = 91.227 (1)°
V = 1020.22 (9) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.36 × 0.35 × 0.09 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS in SAINT-Plus; Bruker, 2003 ▶) T _min = 0.867, T _max = 0.991
10512 measured reflections
5041 independent reflections
4839 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.120
S = 1.11
5041 reflections
515 parameters
3 restraints
H-atom parameters constrained
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: SMART for WNT/2000 (Bruker, 2002 ▶); cell refinement: SAINT-Plus (Bruker, 2003 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXTL and publCIF (Westrip, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809028700/fl2257sup1.cif

e-65-o1992-sup1.cif^{(30.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809028700/fl2257Isup2.hkl

e-65-o1992-Isup2.hkl^{(246.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1B—H1B⋯O3Bⁱ	1.00	2.53	3.362 (3)	141
C2A—H2A⋯O3A	1.00	2.26	2.701 (3)	105
C2B—H2B⋯O3B	1.00	2.26	2.698 (3)	105
C3A—H3A⋯O3Aⁱⁱ	1.00	2.32	3.214 (3)	149
C3B—H3B⋯O3Bⁱ	1.00	2.27	3.165 (3)	148
C4A—H4A⋯O5A	1.00	2.56	3.046 (3)	110
C4A—H4A⋯O7A	1.00	2.23	2.682 (3)	106
C4B—H4B⋯O5B	1.00	2.57	3.067 (3)	110
C4B—H4B⋯O7B	1.00	2.21	2.670 (3)	106
C7A—H7A⋯N3Aⁱⁱ	0.95	2.39	3.308 (4)	161
C7B—H7B⋯N3Bⁱ	0.95	2.40	3.313 (4)	161
C14A—H14A⋯O1Aⁱⁱⁱ	0.98	2.47	3.377 (3)	154
C14B—H14D⋯O1Bⁱⁱⁱ	0.98	2.35	3.261 (3)	155
C16A—H16A⋯O7Bⁱⁱⁱ	0.98	2.41	3.295 (4)	150
C16B—H16F⋯O7A	0.98	2.51	3.401 (4)	150

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

The authors thank the National Institutes of Health (grant R15 AI053112–01) for funding this study. The diffractometer was funded by NSF grant 0087210, by Ohio Board of Regents grant CAP-491, and by YSU.

supplementary crystallographic information

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-1,2,3-triazoles, the title compound was found to be the only 1,2,3-triazole product formed from the reaction of 2,3,4-tri-O-acetyl-β-L-fucopyranosyl azide (Zhang et al., 2007) with 1-hexyne and catalytic CuSO₄/ascorbic acid (Fig. 1).

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 ¹H NMR spectrum of the crude reaction mixture did not show any additional signals that may indicate the formation of the corresponding 1,5-isomer.

The molecules arrange in the solid state in layers with mainly hydrophobic 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 oxygen atoms as the H bond acceptors (Fig. 4, Table 1). The triazole units interact with each other via C—H···N hydrogen bonds that connect the molecules into two infinite chains made up of either A molecules or B molecules that stretch parallel to each other along the [1 0 0] direction (Figure 4, 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 CuSO₄ (0.3 ml, 0.3 mmol), 1M ascorbic acid (0.4 ml, 0.4 mmol) and 10 ml of 1:1 ethanol/H₂O 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. Purification by flash column chromatography (1:1, hexane-ethyl acetate) and recrystallization with isopropanol gave the title compound as a white solid (0.42 g, 83.3%). Crystals suitable for data collection were grown by slow evaporation from isopropanol. ¹H NMR (CDCl₃): δ 0.91 (t, 3H, J = 7.32 Hz), 1.23 (d, 3H, J = 6.22 Hz), 1.35 (m, 2H, J = 7.32 Hz), 1.64 (m, 2H, J = 7.32 Hz), 1.85 (s, 3H, COCH₃), 1.98 (s, 3H, COCH₃), 2.22 (s, 3H, COCH₃), 2.70 (t, 2H, J = 7.32 Hz), 4.09 (q, 1H, J = 6.59 Hz), 5.21 (dd, 1H, J = 2.93, 10.25 Hz), 5.37 (d, 1H, J = 3.30 Hz), 5.50 (t, 1H, H-2, J = 9.89 Hz), 5.76 (d, 1H, H-1, J = 9.89 Hz), 7.54 (s, 1H, H-triazole); ¹³C NMR (CDCl₃): δ 15.08, 17.33, 21.55, 21.83, 21.96, 23.45, 26.56, 32.53, 69.01, 71.07, 72.45, 73.75, 87.32, 119.86, 150.02, 170.20, 170.90, 171.39; MS: m/z calculated: 397.18, m/z found (ESI): 420.2 (+Na).