The crystal structures of two isomers of 5-(phenylisothiazolyl)-1,3,4-oxathiazol-2-one

The 3,5-isomer of the title compound contains two almost planar molecules in the asymmetric unit, whereas the 3,4-isomer contains a single substantially twisted molecule. Both crystal structures feature short S⋯N and S⋯O interactions.


Chemical context
Compounds containing the isothiazolyl moiety are well known in organic and pharmacological research, with extensive reviews on the synthesis and chemistry of the ring (Abdel-Sattar & Elgazwy, 2003) and the medicinal and industrial uses of compounds containing the isothiazolyl heterocycle (Kaberdin & Potkin 2002). The solid-state structural features of isothiazole derivatives have been reviewed (Abdel-Sattar & Elgazwy, 2003). In general, the isothiazolyl ring is recognised as a heteroaromatic ring with extensive -delocalization (incorporating the empty sulfur 3d-orbitals) within the ring leading to almost planar heterocycles.
Derivatives of the oxathiazolone heterocycle have been known since their first preparation fifty years ago (Muhlbauer & Weiss, 1967). The facile synthesis of the heterocycle from commercially available amides reacting with chlorocarbonyl sulfenyl chloride under a range of conditions has resulted in the publication of significant libraries of substituted oxathiazolone compounds (Senning & Rasmussen, 1973;Howe et al., 1978;Lin et al., 2009;Fordyce et al., 2010;Russo et al., 2015) leading to hundreds of known oxathiazolone derivatives. The predominant chemistry of the heterocycle has been the thermal cycloreversion to the short lived nitrile sulfide [R-C N (+) -S (À) ] , a propargyl allenyl 1,3-dipole, which can be ISSN 2056-9890 trapped by electron-deficient bonds in reasonable yield to give families of new heterocycles (Paton, 1989), including isothiazole derivatives. As a result of the electronic properties of the short-lived nitrile sulfide intermediates, optimal conditions for cyclization require trapping reactions with electrondeficient dipolariphiles. Industrially, various derivatives of the oxathiazolone heterocycle have been reported as potential fungicides (Klaus et al., 1965), pesticides (Hö lzl, 2004) and as polymer additives (Crosby 1978). More recently, the medicinal properties of the oxathiazolone heterocycle have been explored as selective inhibitors for tuberculosis (Lin et al., 2009), inflammatory diseases (Fan et al., 2014) and as proteasome inhibitors (Russo et al., 2015).
In previous structural studies on oxathiazolone compounds, the non-aromatic heterocyclic rings were found to be planar with largely localized C N and C O double bonds. The extent of -delocalization within the oxathiazolone ring and to the substituent group and the effect on the structure and chemical properties have been discussed spectroscopically (Markgraf et al., 2007) and structurally (Krayushkin et al., 2010a,b). Our interest in this system was prompted by the possibility that catenated systems of isothiazolone heterocycles may have useful electronic properties as the number of systems is increased.

Structural commentary
There are two independent molecules in the asymmetric unit of (I) (Fig. 1). In general, the two molecules are not significantly different with the exception of the C-S bonds in the oxathiazolone rings. In one of the molecules, the C1-S1 distance [1.762 (2) Å ] is longer than the same bond in the second molecule, C12-S3 [1.746 (2) Å ]. The difference may arise from the nature of the intermolecular contacts to the sulfur atoms, with a strong pair of co-planar SÁ Á ÁN contacts [3.086 (2) Å ] in the first molecule but only one SÁ Á ÁN contact [3.072 (2) Å ] in the second molecule (which is also twisted out of the plane of the molecule). These differences are due to the position of the independent molecules in the tetramer that will be described below. For the purposes of further structural analysis, we will restrict our discussion to the first molecule in the asymmetric unit. The asymmetric unit of (II) is shown in Fig. 2. The bond distances and angles within the terminal phenyl rings in compounds (I) and (II) are not significantly different from the those reported for related compounds (Schriver & Zaworotko, 1995;Krayushkin et al., 2010a,b). The sum of the endocyclic bond angles in the isothiazole moieties for both (I) and (II) (540.0 ) is consistent with planar (ideal sum = 540 ) -delocalized five-membered rings, as expected. The bond lengths of the endocyclic bonds in the isothiazolyl moieties in The molecular structure of (I), showing 50% probability displacement ellipsoids.

Figure 2
The molecular structure of (II), showing 50% probability displacement ellipsoids. statistical averages from previous structural studies (Bridson et al., 1994(Bridson et al., , 1995. While the C N bonds in the isothiazolyl rings of ( The bond distances and angles within the oxathiazolone rings in compounds (I) and (II) are not significantly different ( ! 3) from the statistical averages for published crystal structures (Schriver & Zaworotko, 1995;Bridson et al. 1994Bridson et al. , 1995Vorontsova et al., 1996;McMillan et al., 2006;Krayushkin et al., 2010a,b;Nason et al., 2017). The sum of the endocyclic bond angles in the oxathiazolone rings for both (I) and (II) (540.0 ) is consistent with planar rings (ideal sum = 540 ). The S-N bonds in the oxathiazolone rings of (I) The three rings in the molecules of (I) are nearly co-planar, with the dihedral angles between central isothiazolyl ring and the pendant oxathiazolone and phenyl rings being 3.06 (11) and 1.10 (12) , respectively, for the S1 molecule and 2.62 (9) and 6.84 (10) , respectively, for the S3 molecule. Overall r.m.s. deviations for the S1 and S3 molecules are 0.032 and 0.063 Å , respectively. In contrast to the near planarity of both asymmetric molecules of (I), the single molecule of (II) features significant twists between the central isothiazolyl ring and the pendant oxathiazolone and phenyl rings [dihedral angles of 13.27 (6) and 61.18 (7) , respectively], which may be ascribed to steric crowding. It has been argued, based on spectroscopic and structural evidence, that -delocalization extends between the rings of oxathiazolone heterocycles attached to aromatic rings, resulting in observable differences (Schriver & Zaworotko, 1995;Krayushkin et al., 2010a,b;Markgraf et al., 2007). In this work it can be seen that nearly identical molecules result, even when torsion angles are present that would effectively disrupt any conjugation between the rings, suggesting that the presence or absence of inter-ring delocalization does not have a significant effect on the structure of the molecules.

Supramolecular features
In all previous reports on the solid-state structures of compounds containing the oxathiazolone heterocycle, the intermolecular interactions have been ignored or described as insignificant, with the exception of the recent observation of  -stacking in the styryl derivative (Nason et al., 2017). The strongest intermolecular contacts in (I) are S3Á Á ÁN3 [3.086 (2) Å ], S1Á Á ÁN4 [3.072 (2) Å ] and S4Á Á ÁO1 [3.089 (1) Å ] (Fig. 3). The S3Á Á ÁN3 contacts assist in the formation of a coplanar pair of identical molecules within the asymmetric unit. The other molecules in the asymmetric unit are connected via the S1Á Á ÁN4 [3.072 (2) Å ] and S4Á Á ÁO1 [3.089 (1) Å ] contacts. Taken together, the contacts between two pairs of identical molecules in the asymmetric unit form a centrosymmetric tetramer that in turn form -stacks parallel to the a axis. The intermolecular contacts between sulfur and nitrogen and oxygen have been observed in another oxathiazolone ring that also resulted in -stacking of the planar molecules (Nason et al., 2017).
The strongest intermolecular contacts in (II) are S2Á Á ÁO2 [3.020 (1) Å ], S1Á Á ÁC10 [3.299 (2) Å ] and C4Á Á ÁO2 [3.100 (2) Å ] (Fig. 4). The C4Á Á ÁO2 contact, while significantly shorter than the sum of van der Waals radii for the atoms, is to some extent, the result of the adjacent stronger S2Á Á ÁO2 contact. The geometry of the molecule (II) reduces the opportunity for the formation of -stacks but it is observed that the centroid of the terminal phenyl ring is 3.632 (2) Å above and parallel to the nearly planar portion of an adjacent molecule formed by the two heterocyclic rings (Fig. 4).

Database survey
A search of the Cambridge Structural Database (Version 5.38; Groom et al., 2016) revealed that eleven crystal structures of oxathiazolone derivatives in peer-reviewed journals have been reported previously (Bridson et al., 1994(Bridson et al., , 1995Schriver & Zaworotko, 1995;Vorontsova et al., 1996;McMillan et al., 2006;Krayushkin et al., 2010a,b;Nason et al., 2017), which have been partially reviewed (McMillan et al., 2006 andKrayushkin et al., 2010a,b). An additional five X-ray oxathiazolone crystal structures have been reported in theses (Demas, 1982;Zhu, 1997). There are also two published gasphase electron-diffraction structures of oxathiazolone derivatives (Bak et al., 1978(Bak et al., , 1982. The structures fall into two groups: those that feature a Csp 2 -Csp 3 bond between the heterocycle and the saturated organic substituent and those that feature a Csp 2 -Csp 2 bond between the heterocycle and the unsaturated organic substituent (either a phenyl group, heterocyclic ring or alkenyl moiety).

Synthesis and crystallization
Compound (I) was prepared following a local variation of literature methods (Howe et al., 1978). 3-Phenylisothiazole-4carbonamide (Zhu, 1997) (2.90 g, 14.2 mmol) was placed in 50 ml of toluene under nitrogen and chlorocarbonyl sulfenyl chloride (4.20 g, 32.0 mmol, approximately 2 Â molar excess) was added dropwise to the stirred solution. The resulting mixture was heated (363-373 K) under nitrogen for 1.5 h and allowed to evaporate to a solid residue. The evaporate was recrystallized from toluene solution to give colourless needleshaped crystals (Fig. 5)  A photograph of crystals of (I) (5 Â 5 mm background grid).

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.