2-O-Monoalkyl isosorbide ethers with C8, C10, C12 and C14 chain lengths

The crystal structures of 2-O-monooctyl isosorbide, 2-O-monodecyl isosorbide, 2-O-monododecyl isosorbide and 2-O-monotetradecyl isosorbide are reported. All four compounds crystallize in the chiral space group P21.


Chemical context
We are interested in the synthesis and characterization of amphiphiles and liquid crystals based on renewable resources with a special focus on glycolipid structures. The molecules of the reported crystal structures are precursor compounds to possible liquid crystals, which may already present some liquid crystal properties. The exact geometric shape of the molecule under consideration is decisive for the explanation of observed desired liquid crystal properties. (Vill et al., 1988;Vill et al., 1989;Etzbach et al., 1995). These reported precursors and their corresponding endo-isomers (5-O-alkylisosorbide) were also examined for thermotropic and lyotropic liquid crystal properties. In contrast to the exo-isomers presented here, the endo-isomers are colorless fluids at standard conditions for temperature and pressure. The exo-isomers crystallize in colorless needles at given conditions. ISSN 2056-9890

Structural commentary
The Flack parameters and associated e.s.d. values in the title compounds are À0.7 (5) (3a), À0.18 (13) (3b), 1.6 (9) (3c) and À1.1 (10) (3d). None of the esd values meets the criterion for enantiopure-sufficient inversion-distinguishing power (Flack & Bernardinelli, 2000), which is expected given that compounds 3a, 3b and 3d were measured using Mo radiation and Friedif values are in the range of 6 to 7 (Mo) and 33 to 35 (Cu), respectively (Flack et al., 2007;Flack, 2008). Absolute configurations were thus established from unchanging chiral centers of enantiopure starting materials (_chemical_ absolute_configuration syn). The Flack parameter of the reported compounds is essentially inconclusive. Nevertheless, the structure analysis confirms the formation of compound 3ad. Fig. 1 shows compound 3d with a chain length of C 14 . The other compounds with chain lengths of C 8 , C 10 and C 12 have a strong structural similarity and are not shown explicitly.

Supramolecular features
Van der Waals forces cause the molecules to stack in layers. A classical intermolecular hydrogen bond is observed (Table 2, Fig. 2) between the polar headgroups of two neighboring layers. Because each polar headgroup functions as hydrogenbond acceptor and donor, the hydrogen bond reinforces the connection between the layers and strengthens the coherence within the layer, interlocking the molecules into a herringbone pattern parallel to the bc plane. The intermolecular torsion Symmetry code: (i) Àx, y + 1 2 , Àz À for 3a and Àx, y À 1 2 , Àz + 1 for 3b, 3c and 3d.

Figure 2
Crystal structure of the title compound 3d with chain length C 14 in the crystal. Ellipsoids represent 50% probability levels.

Figure 3
Packing diagram of 3d projected parallel to the ac plane. Dashed lines indicate the intermolecular hydrogen bonds. Hydrogen atoms not involved in the hydrogen-bonding system are omitted.
Regarding the angle of the intermolecular hydrogen bond O4-H4Á Á ÁO1 i , it can be seen that the angle varies slightly with the chain length of the non-polar chain between 155 and 162 ; the distance between the donor and acceptor of the hydrogen bond also stays roughly the same: 2.823-2.834 Å (Table 2).

Database survey
A search of the Cambridge Structural Database (CSD, version 5.41, update of November 2019; Groom et al., 2016) for isosorbide derivates gave only seven hits, whereby only three hits were mono-substituted: NOZVUW (Sagawa et al., 2019) is the 2-acetamide-2-deoxyisosorbide, PIMKOO (Kanters et al., 1993) is the isosorbide-2-mononitrate and TUQGET (Santschi et al., 2015) the isosorbide-5-mononitrate. Therefore, none of them represent mono-alkyl ethers. PIMKOL (Kanters et al., 1993) is the isosorbide dinitrate of the corresponding isosorbide-2-mononitrate whereas WECBUE (Wu et al., 2017) is the dinitrile. MOVFUY (Harata & Kawano, 2002) is a bis(-cyclodextrin) clathrate of isosorbide dinitrate and TECRIC (Hušá k et al., 1996) is a cyclosporine dimethylisosorbide solvate. Only the latter is an alkyl ether, but disubstituted. Regarding the angle C2-C3-O3 constituted by the annulated tetrahydrofuran rings, it is noticeable that the angles of the reported compounds here are larger than those of the mono-and dinitrates whereas the angle O1-C4-C5 is smaller. The cyclosporine dimethylisosorbide solvate has a larger angle for O1-C4-C5 whereas the angle for C2-C3-O3 is smaller in comparison to compounds presented here. The dinitrile isosorbide shows a comparable angle for the angle O1-C4-C5, but the C2-C3-O3 angle is larger in that compound compared to the mono-alkyl ethers. The same applies to the isosorbide dinitrate clathrate. The 2-acetamide-2-deoxyisosorbide shows angles that are comparable to the mono-alkyl ethers reported here.

Synthesis and crystallization
Isosorbide 1 (30 mmol) and potassium hydroxide (30 mmol) were dissolved under stirring in 15 mL dimethyl sulfoxide at 400 K. Bromo alkane 2 (20 mmol) was added slowly. The solution was kept at 400 K under stirring for 24h. The solution was cooled to room temperature and acidified to pH = 1 with 37% hydrochloric acid. Triple extraction with 50 mL of ethyl acetate and drying the collected organic phases over magnesium sulfate gave a golden-yellow raw product after removal of the solvent under reduced pressure. The raw product was separated and purified by column chromatography (solvent: petroleum ether 50-70/ethyl acetate 1:1). Evaporation of the solvent under reduced pressure afforded compound 3 as colorless crystals and compound 4 as colorless syrup-like fluids in a combined yield of 30 to 50% (Zhu et al., 2008).    Detail of the packing diagram of 3a with the intermolecular torsion angle highlighted in green. The intermolecular torsion angle corresponds to the opening angle of the herringbone pattern. Ellipsoids represent 50% probability levels.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Methyl groups were refined as idealized rigid groups allowed to rotate but not tip (C-H = 0.98 Å and H-C-H = 109.5 ). Other hydrogen atoms were included using a riding model starting from calculated positions (methylene C-H = 0.98 and methine C-H = 1.00 Å ). The U iso (H) values were fixed at 1.5 (for the methyl H and hydroxy H) or 1.2 times the equivalent U iso value of the parent carbon atoms and oxygen atom, respectively.

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.

6-(Dodecyloxy)hexahydrofuro[3,2-b]furan-3-ol (iso-c12)
Crystal data 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq O4 −0.3077 (4) −0.3567 ( 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.