2,3,4,6-Tetra-O-benzoyl-4-nitro­phenyl-1-thio-α-d-mannopyran­oside–dichloro­methane–diethyl ether mixed solvate (1/0.53/0.38)

Ludovic Drouin; Andrew R Cowley; Antony J Fairbanks; Amber L Thompson

doi:10.1107/S1600536807064951

. 2007 Dec 12;64(Pt 1):o236. doi: 10.1107/S1600536807064951

2,3,4,6-Tetra-O-benzoyl-4-nitrophenyl-1-thio-α-d-mannopyranoside–dichloromethane–diethyl ether mixed solvate (1/0.53/0.38)

Ludovic Drouin ^a, Andrew R Cowley ^a, Antony J Fairbanks ^a,^*, Amber L Thompson ^a

PMCID: PMC2915296 PMID: 21200803

Abstract

The title compound, C₄₀H₃₁NO₁₁S·0.53CH₂Cl₂·0.38C₄H₁₀O, was synthesized in two steps from mannose pentaacetate and single crystals were grown by slow evaporation. The structure was determined by single-crystal X-ray diffraction, confirming the α-configuration of the anomeric thioaryl substituent. The asymmetric unit contains two crystallographically distinct molecules of the carbohydrate. The central pyranose rings of these are geometrically similar, but there are differences in the orientations of the benzoate substituents.

Related literature

For related literature, see: Cao et al. (1998 ▶); Shah & Bahl (1974 ▶); Cosier & Glazer (1986 ▶); France et al. (2004 ▶); Mootoo et al. (1988 ▶); Prince (1982 ▶); Roy et al. (1992 ▶); Watkin (1994 ▶).

Experimental

Crystal data

C₄₀H₃₁NO₁₁S·0.534CH₂Cl₂·0.382C₄H₁₀O
M _r = 770.56
Monoclinic,
a = 11.7508 (2) Å
b = 20.5564 (3) Å
c = 16.4633 (2) Å
β = 105.8699 (16)°
V = 3825.20 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 150 K
0.34 × 0.28 × 0.24 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ▶) T _min = 0.94, T _max = 0.96
35711 measured reflections
15110 independent reflections
13111 reflections with I > 3σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.056
S = 1.09
13111 reflections
990 parameters
17 restraints
H-atom parameters not refined
Δρ_max = 1.02 e Å⁻³
Δρ_min = −0.92 e Å⁻³
Absolute structure: Flack (1983 ▶), 6226 Friedel pairs
Flack parameter: 0.03 (5)

Data collection: COLLECT (Nonius, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶); data reduction: DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: SHELXTL (Bruker, 2000 ▶); software used to prepare material for publication: CRYSTALS.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536807064951/lw2055sup1.cif

e-64-0o236-sup1.cif^{(43.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807064951/lw2055Isup2.hkl

e-64-0o236-Isup2.hkl^{(753.2KB, hkl)}

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

Acknowledgments

The authors thank the EPSRC (project studentship GR/T24692/01 to LD) for financial support, and Dr Sarah Jenkinson for assistance with the preparation of the manuscript.

supplementary crystallographic information

Comment

Thioglycosides are extremely useful and versatile glycoside donors for the synthesis of oligosaccharides, which may be activated by a wide range of electrophiles and also by electrochemical methods (France et al., 2004). The nature of an aromatic substituent of an aryl thioglycoside has a strongly modulating effect on the reactivity of such a thioglycoside; strongly electron withdrawing substituents greatly reduce their reactivity towards electrophiles (Roy et al., 1992) and also increase their oxidation potentials. Such 'disarmed' (Mootoo et al., 1988) thioglycosides may themselves therefore be used as acceptors for the glycosylation of more reactive 'armed' thioglycoside donors. The title compound was obtained by a trans-esterification sequence from the corresponding peracetylated thioglycoside, itself synthesized from mannose penta-acetate by treatment with 4-nitrothiophenol and boron trifluoride etherate in dichloromethane, by Zemplen deacetylation followed by reaction with benzoyl chloride in pyridine in the presence of N,N-dimethylaminopyridine (DMAP).

Experimental

1,2,3,4,6-Penta-O-acetyl-D-mannopyranoside (2.17 g, 3.55 mmol) and 4-nitrothiophenol (1.75 g, 11.26 mmol) were suspended in anhydrous dichloromethane (15 ml), under an atmosphere of argon, the mixture was cooled to 0°C, and boron trifluoride diethyl etherate (3.3 ml, 26 mmol) was added dropwise. The reaction mixture was then stirred at room temperature until after 66 h, t.l.c. (petroleum ether/ethyl acetate, 1:1) indicated complete consumption of the starting material, and the formation of a single product (Rf 1/2). The reaction was quenched by the addition of triethylamine (10 ml), and the mixture was then partitioned between water (200 ml) and dichloromethane (200 ml). The aqueous layer was re-extracted with dichloromethane (3 x 200 ml), and the combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (200 ml), dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate, 7:3) to afford 4-nitrophenyl 2,3,4,6-tetra-O-acetyl-1-thio-α-D-mannopyranoside (1.98 g, 74%) which recrystallized from petroleum ether/ethyl acetate as a yellow crystalline solid; m.p 134–136°C (petroleum ether/ethyl acetate); lit., 135–136°C (methanol, Shah & Bahl, 1974); [α]_D²³ +158 (c, 0.9 CHCl₃); lit., [α]_D +142.6 (c, 0.93 CHCl₃, Shah & Bahl,(1974): ν_max (KBr) 1752 (νC=O ester), 1513, 1579, 1599 (νArC=C), 1233 (νCO ether), 1066 (νCO ether) cm^-1; δ_H (400 MHz, CDCl₃) 2.03 (3H, s, CH₃CO), 2.04 (3, s, CH₃CO), 2.07 (3H, s, CH₃CO), 2.19 (3H, s, CH₃CO), 4.10 (1H, dd, J_5,6 2.5 Hz, J_6,6' 12.0 Hz, H-6), 4.31 (1H, dd, J_5,6' 6.0 Hz, J_6,6' 12.0 Hz, H-6'), 4.41 (1H, ddd, J_4,5 9.5 Hz, J_5,6 2.5 Hz, J_5,6' 6.0 Hz, H-5), 5.28 (1H, dd, J_2,3 3.5 Hz, J_3,4 10.0 Hz, H-3), 5.37 (1H, at, J_3,4 10.0 Hz, J_4,5 10.0 Hz, H-4), 5.48 (1H, dd, J_1,2 2.0 Hz, J_2,3 3.5 Hz, H-2), 5.70 (1H, d, J_1,2 2.0 Hz, H-1), 7.60 (2 x 1H, 2 x dd, J 7.0 Hz, J 2.0 Hz, 2 x ArH), 8.17 (2 x 1H, dd, J 7.0 Hz, J 2.0 Hz, 2 x ArH); δ_C (100 MHz, CDCl₃) 20.9 (2 x CH₃CO), 21.0 (CH₃CO), 21.1 (CH₃CO), 62.4 (C-6), 66.2 (C-4), 69.4 (C-3), 70.4 (C-5), 70.8 (C-2), 84.3 (C-1), 124.3 (2 x ArCH), 129.8 (2 x ArCH), 142.9 (ArC), 146.9 (ArC), 169.9 (C=O), 170.1 (C=O), 170.1 (C=O), 170.6 (C=O); (HMRS (ESI) Calcd. For C₂₀H₂₇O₁₁N₂S (M+NH₄)⁺ 503.1336. Found 503.1334). (Found: C, 49.49; H, 4.79; N, 2.88. C₂₀H₂₃O₁₁SN requires: C, 49.48; H, 4.77; N, 2.88%).

4-Nitrophenyl 2,3,4,6-tetra-O-acetyl-1-thio-α-D-mannopyranoside, as prepared above, (1.66 g, 3.43 mmol) was dissolved in methanol (26 ml) and sodium methoxide (0.20 g, 3.80 mmol) was added. The reaction mixture was then stirred at 22°C and, after 45 min, t.l.c. (petroleum ether/ethyl acetate, 1:1) indicated complete consumption of the starting material (Rf 0.6) and the formation of a single product (Rf 0.1). Cation exchange resin IR-120 was then added until neutral pH was attained, and then the mixture was filtered and the solvent was removed under reduced pressure. Azeotropic evaporation with toluene (15 ml) furnished the crude product, which was used in the next step without further purification. The residue was dissolved in pyridine (10 ml) and the mixture was cooled to 0°C. Benzoyl chloride (2.5 ml, 21.52 mmol), and N,N-dimethylaminopyridine (97 mg, 0.79 mmol) were added and the reaction mixture was stirred at room temperature for 24 h after which time, t.l.c.(petroleum ether/ethyl acetate, 7:3) indicated complete consumption of the starting material (Rf 0.0) and the formation of three major products (Rf 0.2 identified as 4-nitrothiophenyl 2,3,6-tri-O-benzoyl-α,D-mannopyranoside; Rf 0.3, Rf 0.4 identified as 1,2,3,4,6-penta-O-benzoyl-D-mannopyranoside; Rf 0.5 identified as the desired 4-nitrothiophenyl 2,3,4,6-tetra-O-benzoyl-α,D-mannopyranoside). The mixture was partitioned between water (40 ml) and dichloromethane (70 ml), and the aqueous layer was re-extracted with dichloromethane (3 x 70 ml). The combined organic extracts were washed with aqueous hydrochloric acid (1M, 3 x 70 ml), a saturated aqueous solution of sodium hydrogen carbonate (140 ml), dried over MgSO₄, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate) and then re-crystallized from petroleum ether/ethyl acetate to afford 4-nitrothiophenyl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranoside (934 mg, 37%) as yellow crystals; m.p 119–120°C (from petroleum ether/ethyl acetate); a sample suitable for X-ray analysis was then re-crystallized by slow evaporation of a solution in dichloromethane/diethyl ether; [α]_D²³ +77 (c, 1.0 in CHCl₃); ν_max (KBr) 1728 (νC=O ester), 1452, 1518, 1581, 1600 (νArC=C), 1265 (νCO ester), 1093 (νCO ester), 709 (νArCH) cm^-1; δ_H (400 MHz, CDCl₃) 4.61 (1H, dd, J_5,6 6.0 Hz, J_6,6' 12.5 Hz, H-6), 4.66 (1H, dd, J_5,6' 3.0 Hz, J_6,6' 12.5 Hz, H-6'), 4.93 (1H, dd, J_4,5 10.0 Hz, J_5,6 6.0 Hz, J_5,6' 3.0 Hz, H-5), 5.88 (1H, dd, J_2,3 3.0 Hz, J_3,4 10.0 Hz, H-3), 5.96 (1H, dd, J_1,2 1.5 Hz, J_2,3 3.0 Hz, H-2), 6.04 (1H, d, J_1,2 1.5 Hz, H-1), 6.14 (1H, at, J_3,4 10.0 Hz, J_4,5 10.0 Hz, H– 4), 7.20–8.20 (24 x 1H, m, 24 x ArH); δ_C (100 MHz, CDCl₃) 60.6 (C-6), 63.0 (C-4), 67.0 (C-3), 70.4 (C-5), 71.6 (C-2), 84.0 (C-1), 124.3 (2 x ArCH), 128.6 (2 x ArCH), 128.8 (2 x ArCH), 128.9 (2 x ArCH), 129.1 (2 x ArC), 129.5 (2 x ArCH), 129.6 (2 x ArC), 129.8 (2 x ArCH), 130.0 (2 x ArCH), 130.1 (2 x ArCH), 130.1 (2 x ArCH), 130.2 (2 x ArCH), 133.6 (ArCH), 133.7 (ArCH), 133.9 (ArCH), 134.0 (ArCH), 142.6 (ArC), 146.7 (ArC), 165.5 (C=O), 165.7 (2 x C=O), 166.1 (C=O); m/z (ESI) 792.12 ([M+NH₄+CH₃CN]⁺, 100%). (Found: C, 65.40; H, 4.78; N, 1.98; S, 4.27. C₄₀H₃₁O₁₁SN requires: C, 65.48; H, 4.26; N, 1.91; S, 4.37%).