Structures of rac-2,4:3,5-dimethylene xylitol derivatives

The crystal structures of three xylitol derivatives prepared directly from commercially available xylitol by treatment with formalin and acid followed by subsequent derivatization of the primary hydroxyl group of the bis-methylene ketal with mesyl chloride, benzyl bromide or phenyl isocyanate are reported.


Chemical context
Naturally occurring monosaccharides provide an abundant source of inexpensive, often chiral, starting materials for the syntheses of numerous sophisticated natural products, nonnatural physiologically active compounds, and ligands for stereoselective catalysts (Ferrier, 2003).Over the past decade or so, a sharply increasing emphasis is seen on the use of these sugars and also on chemical transformations among the various diastereomeric and homologous series of monosaccharides.Despite this flurry of activity, monosaccharide derivatives still provide a rich source of challenging structural and conformational issues due to the anomeric and gauche interactions associated with the O atoms.
In this article, we describe the crystal structures of three cisfused [4.4.0]bicyclo methylene acetals originally derived from the most inexpensive and readily available five-carbon meso polyalcohol, i.e. xylitol.The chemical structures of these compounds are shown in the scheme.The standard chemical numbering for the 1,3,5,7-tetraoxadecalin ring system is shown in Fig. 1.The atoms in all three crystal structures reported are labeled following this pattern.Compound 1 is a mesylate, with R = mesyl (Zarubinskii & Danilov, 1972), compound 2 is a benzyl ether, with R = benzyl (Che et al., 2017), and compound 3 is an N-phenylurethane, with R = -CO-NH-Ph.Since xylitol itself is achiral and we carried out no enantioselective reactions to prepare chiral derivatives, the structures we report are of racemates and hence centrosymmetric, although it is possible to obtain enantiomerically pure compounds from more complicated synthetic routes.

Structural commentary
The defining characteristic of the cis-1,3,5,7-tetraoxa-[4.4.0]bicyclodecalin ring system is depicted in Figs. 2 and 3. Fig. 2 illustrates the two lowest-energy all-chair conformations of this skeleton.The O atoms in these conformers adopt a tetrahedral geometry and the axial lone pair of electrons on each of these O atoms within the decalin ring are depicted.This feature was noted previously (Lemieux & Howard, 1963;Burkert, 1980;Taskinen, 2009) and described in detail in a mini-review summarizing over two decades of chemical work largely from one laboratory (Fuchs, 2013).Trivial nomenclature has evolved to describe these two conformations as inside/concave or outside/convex.These descriptions derive from the orientation of the axial lone pairs on the ring O atoms relative to the overall shape of the decalin ring system.For the completely unsubstituted tetraoxydecalin, it is not immediately obvious which of these two conformers is more stable.
Compounds 1-3 also incorporate a derivatized hydroxymethyl substituent at position C4 that is trans to both bridgehead H atoms. Consequently, this substituent must be equatorial in the concave/inside conformer and axial in the convex/outside conformer.Conformational analysis suggests that the concave/inside conformer is favored, as seen in all these crystal structures.Fig. 3 highlights this overall geometry found in all three crystal structures.The overall shape of this molecule resembles a cylinder that has been cut in half.It is noteworthy that this molecular shape has been examined for its potential to chelate cations as a polydentate ligand (Ganguly & Fuchs, 2001) and also as a cryptand (Abramson et al., 2003).
Fig. 4 is an overlay of all three crystal structures obtained by minimizing the positional differences of the four ring O atoms in all three structures.No significant difference in the geometry of the tetraoxabicyclic ring in these three structures is discernible.It is noteworthy that a gauche conformation is found for the O3-C4-C9-O8 torsion angle, with values of 61.8 (2) and 81.6 (1) in mesylate 1 and benzyl ether 2, respectively.However, a relatively antiperiplanar torsion angle of 175.9 (8) exists in urethane 3.This is likely the consequence of stabilization by the single intermolecular research communications Acta Cryst.(2023).E79, 786-790 Satlow and Williard C 8 H 14 O 7 S, C 14 H 18 O 5 and C 14 H 17 NO 6 787 Figure 2 Stable conformations of cis-1,3,5,7-tetraoxa-[4.4.0]bicyclodecalin.
hydrogen bond observed in the urethane structure (see below).
No other hydrogen-bond interactions are possible in any of the structures, although there are short C-HÁ Á ÁO interactions between the H2B atom on a methylene acetal and an adjacent acetal O5 ii atom [symmetry code: (ii) x, Ày + 3 2 , z + 1 2 ] in urethane structure 3 that is characteristically seen in all of the structures.This is characterized in Table 1.
No -stacking interactions of the aromatic rings are observed.

Figure 8
Hydrogen bonding in compound 3.

Synthesis and crystallization
Compounds 1 and 2 were prepared and crystallized by the following general procedure.To a solution of racemic 2,4:3,5dimethylene xylitol (Hann et al., 1944) in pyridine, 1.1 molar equivalents of either mesyl chloride or benzyl bromide were added and stirred at room temperature until the diacetal dissolved ($4 h).The resulting reaction mixtures were allowed to stand for 18 h at room temperature and then poured onto crushed ice.Solid crystalline material formed upon slow evaporation of the reaction mixture on sitting in a fume hood overnight.Recrystallization from ethanol produced diffraction-quality crystals. 1H and 13 C NMR spectra of the crystalline samples indicated no discernible impurities and are provided in the supporting information.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were added automatically using a riding model with U iso (H) = 1.2U eq (C).The H atom on N1 in urethane 3 was located in a difference Fourier map and refined freely.

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

A search of the Cambridge Structural Database (CSD, Version 5.43, update of November 2021; Groom et al., 2016) 788
Satlow and Williard C 8 H 14 O 7 S, C 14 H 18 O 5 and C 14 H 17 NO 6

Table 2
Krause et al., 2015).Experiments were carried out at 173 K with Mo K radiation.Absorption was corrected for by multi-scan methods (SADABS;Krause et al., 2015).