2,6-Anhydro-1,3-di-O-benzyl-d-mannitol

Edmilson Clarindo de Siqueira; Bogdan Doboszewski; James McGarrah; Alexander Y Nazarenko

doi:10.1107/S1600536811022306

. 2011 Jun 18;67(Pt 7):o1653–o1654. doi: 10.1107/S1600536811022306

2,6-Anhydro-1,3-di-O-benzyl-d-mannitol

Edmilson Clarindo de Siqueira ^a, Bogdan Doboszewski ^a, James McGarrah ^b, Alexander Y Nazarenko ^c,^*

PMCID: PMC3152021 PMID: 21837055

Abstract

In the title compound, C₂₀H₂₄O₅, the six-membered pyranose ring adopts a chair conformation. The dihedral angle between the planes of the phenyl groups of the benzyl substituents is 63.1°. Two types of intermolecular O—H⋯O hydrogen bonds lead to the formation of infinite chains along the b axis. Only weak C—H⋯O contacts exist between neighboring chains.

Related literature

For syntheses of this and similar compounds, see: Barker (1970 ▶); Doboszewski (1997 ▶, 2009 ▶); Doboszewski & de Siqueria (2010 ▶); Hartman (1970a ▶,b ▶). For related structures, see: Boeyens et al. (1983 ▶); Doboszewski & Nazarenko (2003 ▶); Guiry et al. (2008 ▶); Hong et al. (2005 ▶); Vidra et al. (1982 ▶). For conformations of six-membered rings, see: Schwarz (1973 ▶); Cremer & Pople (1975 ▶); Boeyens & Dobson (1987 ▶). For hydrogen bonding in carbohydrate chemistry, see Gilli & Gilli (2009 ▶); Desiraju & Steiner (1999 ▶); Jeffrey (1997 ▶), and references therein.

Experimental

Crystal data

C₂₀H₂₄O₅
M _r = 344.39
Monoclinic,
a = 5.6584 (10) Å
b = 7.9610 (12) Å
c = 19.808 (4) Å
β = 91.968 (6)°
V = 891.8 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 200 K
0.6 × 0.4 × 0.05 mm

Data collection

Bruker SMART X2S diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2008b ▶) T _min = 0.91, T _max = 0.98
8624 measured reflections
1695 independent reflections
1458 reflections with I > 2σ(I)
R _int = 0.052

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.082
S = 0.99
1695 reflections
228 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Data collection: GIS (Bruker, 2010 ▶); cell refinement: APEX2 (Bruker, 2010 ▶) and SAINT (Bruker, 2009 ▶); data reduction: SAINT and XPREP in SHELXTL (Sheldrick, 2008a ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008a ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008a ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1999 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811022306/zl2379sup1.cif

e-67-o1653-sup1.cif^{(20.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811022306/zl2379Isup2.hkl

e-67-o1653-Isup2.hkl^{(83.5KB, hkl)}

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

Enhanced figure: interactive version of Fig. 5

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯O5ⁱ	0.84	1.95	2.789 (2)	175
O5—H5⋯O2ⁱ	0.84	1.98	2.812 (2)	169
C6—H6B⋯O5ⁱⁱ	0.99	2.54	3.461 (3)	155

Open in a new tab

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

Acknowledgments

This study was supported by a grant for the X-ray diffractometer and by SUNY grant No. 1073053. AYN thanks Dr Bruce Noll (Bruker AXS) for useful advice in operating the X2S diffractometer, and Dr David Geiger (SUNY Geneseo) for help with the experiment.

supplementary crystallographic information

Comment

A target compound of our (BD and ECS) synthetic research, 2,5-anhydro-D-glucitol (compound 2 in Fig. 1) is technically a β-C-glycoside of D-arabinofuranose. We prepared it in its protected form 4 starting from 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride or bromide (Doboszewski, 1997, 2009). The structure of 4 was confirmed by X-ray crystallography (Doboszewski & Nazarenko, 2003). Since this procedure furnished low and variable yields, we focused our attention on an alternative method, i.e. acid-catalyzed dehydration of D-mannitol 1 (Barker, 1970; Hartman, 1970a,b; Doboszewski & de Siqueria, 2010). The original patented procedure (Hartman, 1970a,b) was modified by using vacuum-dry chromatography to isolate the acetonide 4, which was subsequently used to obtain the corresponding di-O-benzyl derivative 8 (Doboszewski, 1997). During the synthesis of 8 at a ca 30 g scale (see Fig. 1) we have noticed the presence of a minor byproduct which is more polar than the expected 8. This compound was formed in a very low yield (ca 1%) and its ¹H NMR spectrum was practically intractable and showed an aromatic:aliphatic H atom ratio of 1:1.4. Using single-crystal X-ray diffraction (this present study) it was identified as 2,6-anhydro-1,3-di-O-benzyl-D-mannitol 9. Evidently, the main cyclization route to form 2,5-anhydro-D-glucitol 2 was accompanied by a minor pathway to form 3 together with other dehydration products (Barker, 1970). Both acetonides 4 and 5 migrated jointly during chromatography, but become separable after transformation into the corresponding di-benzyl ethers 8 and 9, respectively (Fig. 1).

The absolute structure of the title compound is known from the synthetic route which does not affect stereogenic atoms of the starting D-mannitol. In the crystal structure of title compound (Fig. 2), all bond lengths and bond angles have standard dimensions. The high flexibility of the oxymethylene fragment results in elongated thermal ellipsoids of atoms O1 and C10.

The six-membered phenyl rings are flat within 0.01 Å. Fig. 3 shows that the pyranose ring adopts a chair conformation (Schwarz, 1973) with atoms C1, C2, C5, and C6 being within 0.01 Å from their mean plane, and atoms O1 and C4 at a distances of 0.68 and 0.64 Å. A quantitative analysis of the ring conformations was performed using the method of Cremer and Pople (Cremer & Pople, 1975; Boeyens & Dobson, 1987) for the calculation of parameters of puckering. The polar parameters for the pyranose ring are Q = 0.576 (2) Å, Θ = 175.8 (2)°, and Φ = 207 (3)°. These suggest a chair conformation (ideal Θ = 0 or 180°) only slightly distorted towards half-chair (Θ = 130°, Φ = 210°). There are four compounds reported in Cambridge Structure Database with the same motif: 1,5-anhydro-DL-galactitol (refcode ANGALA10, Vidra et al., 1982) 1,5-anhydro-D-glucitol (CELTUI, Boeyens et al., 1983), (+)-ethyl-3-(acetoxy)-4,5-dihydroxytetrahydro-2H-pyran-2-carboxylate (FIQWAE, Hong et al., 2005) and 1-deoxy-D-lactose (XOJLUE, Guiry et al., 2008). In all these structures, the six-membered ring has a chair conformation.

Two hydroxy groups and an O atom of the pyranose ring form a system of O—H··· O hydrogen bonds that leads to the formation of an infinitive chain along the b axis (Table 1, Fig. 4). These hydrogen bonds of intermediate strength (Gilli & Gilli, 2009) result in a decrease of the O—H stretching vibrations frequency from the theoretical 3500 cm^-1 for a "free" OH group to 3330 cm^-1.

Only weak C—H···O (Table 1) contacts exist between neighboring chains. Similar bonds were observed in various carbohydrates (Desiraju & Steiner, 1999). A short intramolecular contact between oxygen O3 and H atom H1A of neighboring methylene group may additionally stabilize the conformation of the molecule.

Experimental

Crystals of the title compound were obtained as a side product of dehydration of D-mannitol (Fig. 1) in the form of thin plates (m.p. 454 (3) K) by spontaneous crystallization after chromatographic separation using a gradient of ethylacetate in hexane. A suitable crystal was cut out of a larger plate. Data collection was limited to θ = 25° because of the geometry of the instrument.

Exact mass MS (ESI): calc. for C₂₀H₂₄O₅ +Na⁺: 367.1516; found 367.1507.

Optical rotation: α_D +7.4° c 2.6 (DMSO)

¹H NMR (300 MHz, DMSO-d₆): 7.37–7.25 (H aromatic, 10H), 4.86 (d, J = 6.3 Hz, 1H, exchangeable), 4.83 (d, J = 11.1 Hz, 1H), 4.65 (d, J = 3.6 Hz, exchangeable), 4.51 (d, J = 11.6 Hz, 2H), 4.44 (d, J = 12.1 Hz, 1H), 3.76–3.39 (unresolved, 7H), 3.27–3.21 (unresolved, 1H).

¹³C NMR: 139.02, 138.42, 128.21, 128.10, 127.63, 127.39, 127.28, 78.66, 75.98, 74.36, 73.76, 72.33,* 69.77,* 69.69,* 69.29 (* negative signals in the Attached Proton Test).

FT–IR (Nicolet 400, diamond ATR): 3330 (very strong), 3064, 3033, 2916, 2862, 1495, 1452, 1328, 1082, 1067, 890, 692, 606, 530 cm^-1.

Raman (Raman Systems 2.0; 785 nm laser): 1603, 1466, 1342, 1278, 1202, 1174, 1004 (very strong), 945, 821, 617, 431, 186 cm^-1.