Crystal structures of 4,4′-(disulfane-1,2-diyl)bis(5-methyl-2H-1,3-dithiol-2-one) and 4,4′-(diselanane-1,2-diyl)bis(5-methyl-2H-1,3-dithiol-2-one)

By in situ oxidation (S—S)2− and (Se—Se)2− moieties are formed, replacing nBu3Sn substituents on alkene carbon atoms of two distinct and subsequently linked 1,3-ene-dithiol-2-one units. The resulting compounds, bis[4-methyl-1,3-dithiol-2-one] disulfide, C8H6O2S4S2, and bis[4-methyl-1,3-dithiol-2-one] diselenide, C8H6O2Se6, are isotypic.


Chemical context
Selenium-and sulfur-containing compounds play an important role in nature. Sulfur-rich compounds, in particular derivatives of tetrathiafulvalene and dithiolene, comprise chemically interesting compounds with exceptional electronic structural characteristics. Selenium is an essential trace element in the active sites of several enzymes and plays inter alia an important role in antioxidant selenoproteins for protection against oxidative stress such as in thioredoxin reductase (Lee et al., 1999;Lescure et al., 1999;Mustacich & Powis, 2000;Watabe et al., 1999;Williams et al., 2000). In the disulfide isomerase protein family, thioredoxin-like domains are rich in cysteine residues. A diselenide from selenocysteins was shown to be structurally very similar to the respective disulfide from two cysteins (Gö rbitz et al., 2015). As a consequence, disulfide and diselenide compounds were developed as catalysts for oxidative protein folding and refolding reactions (Arai et al., 2018). Here we report the serendipitous synthesis and structural characterization of bis[3-methyl-1,3-ene-dithiol-2-one] disulfide and bis[3-methyl-1,3-ene-dithiol-2-one] diselenide via unprecedented routes. Instead of the targeted products, the applied order of reactions yielded the novel disulfide and its diselenide analogue, which have potential applications in redox chemistry and as biologically interesting compounds. By in situ oxidation, S-S or Se-Se moieties are formed, replacing the n Bu 3 Sn substituents of alkene carbon atoms of two distinct and consequently linked 1,3-ene-dithiol-2-one units. As this constitutes a substitution of a n Bu 3 Sn functional ISSN 2056-9890 group, it is quite likely that this method can be applied to a variety of respective different precursors.

Structural commentary
The two title compounds are isotypic. One complete molecule constitutes the asymmetric unit despite being chemically perfectly symmetric: i.e. no symmetry operation is used to generate the whole molecular structure. In both compounds, two 3-methyl-1,3-ene-dithiol-2-one moieties are linked by a dichalcogenide bridge (S 2 2À or Se 2 2À ), which is attached to one of the ene carbon atoms, while the other ene carbon is bound to a methyl group (Figs. 1 and 2). Both structures constitute the first examples of crystallographically characterized disulfides and diselenides in which two 1,3-ene-dithiol-2-one moieties are linked by a dichalcogenide bridge. While related bridged 1,3-ene-dithiol-2-thione moieties are reported for disulfides and also one compound in which the disulfide is part of a heterocycle with the 1,3-ene-dithiol-2-one moiety (Chou et al., 1998), no such analogues are known in the case of the diselenide bridge.
The metrical parameters of both molecules are nearly identical (see Fig. 3 for an overlay of the molecules), with the largest differences found for the dichalcogenide bridge itself. The Se-Se distance [2.3397 (7) Å ] is longer by ca 0.27 Å than the S-S distance [2.0723 (7) Å ], matching almost exactly the difference in the respective covalent radii (0.13 Å ; Pyykkö & Atsumi, 2009) multiplied by two. Similarly, the average C-Se distance [1.897 (4) Å ] is longer by 0.15 Å than the average C-S distance [1.749 (2) Å ]. Unusual electronic effects upon exchanging selenium for sulfur can, hence, be excluded. The average C-Se-Se angle [98.8 (6) ] is slightly more acute than the C-S-S angle [101.8 (6) ], which necessarily results from the longer distances involving the Se atom and the nearly identical atom positions of the 1,3-ene-dithiol-2-thione moieties. All other differences in the metrical parameters between the two molecular structures are marginal. All observed distances and angles also fall into or close to the expected/previously reported ranges. The S-S distances of the most closely related compounds range from 2.078 Å in an Fe(CO) 2 Cp-coordinating species (Matsubayashi et al., 2002) to 2.160 Å in the [C 6 S 10 ] 2À dianion crystallized as an ammonium salt (Breitzer et al., 2001). The observed S-S distance [S3-S4; 2.0723 (7) Å ] here is slightly shorter than the former, though not shorter than the lower limit of ca 2.00 Å when generally evaluating C-S-S-C linkages (Comerlato et al., 2010;Aida & Nagata, 1986). Se-Se distances in compounds in which one Se 2 2À unit binds to alkene carbon atoms and bridges two identical ene-moieties range from 2.303 Å (Biswas  The molecular structure of [bis[4-methyl-1,3-ene-dithiol-2-one] diselenide. Displacement ellipsoids are shown at the 50% probability level.
The structurally most notable features are the C-S-S-C and C-Se-Se-C torsion angles [70.70 (5) and 68.86 (3) , respectively] which bring the two 1,3-ene-dithiol-2-thione moieties in rather close proximity. In related disulfides they range from 52.08 to 109.82 (Breitzer et al., 2001). C-S-S-C torsion angles near 90 were found in silico to stabilize structures by an overlap of one *S-C orbital with the 3p lone pair of the other sulfur atom, which is maximized in such an arrangement (Aida & Nagata, 1986). The observed C-Se-Se-C torsion angles of diselenide-bridged alkenes as the closest relatives of the title diselenide range from 73.03 (Ruban et al., 1981) to 92.04 (Biswas et al., 2017). In the crystalline solid state, apparently packing effects, steric bulk, hydrogen-bonding interactions, and --stacking can influence the relative orientations of the two substituents on the disulfide unit significantly, whereas the values for alkene bridging diselenides observed to date are less varied.

Database survey
In the literature to date, only S-S-bridged 1,3-ene-dithiol-2thione compounds have been reported but no analogous 1,3ene-dithiol-2-one compounds (excluding those in which the 'link' is part of a heterocycle). The first such thione crystal structure was reported in 1999 by Cerrada et al., which comprises an S-S-linked [C 3 S 5 -C 3 S 5 ] 2À dianion (Cerrada et al., 1999). Ten years later, Cerrada et al. described the S-S coupling via dithiolate transfer from tin to nickel complexes where they isolated an S-S-bridged 1,3-dithiol-2-thione with different substituents as a crystalline byproduct (Cerrada et al., 2009). Rauchfuss and co-workers described the isolation and structural characterization of an S-S-linked dianion [C 6 S 10 ] 2À as the tetramethylammonium salt (Breitzer et al., 2001). In 2002, Matsubayashi et al. reported the formation of an S-S-linked [C 3 S 5 -C 3 S 5 ] 2À system bridging two Fe(CO) 2 Cp complexes by coordination of thiolate sulfur to iron (Matsubayashi et al., 2002). Wardell and coworkers carried out the controlled oxidation of cesium 4-benzoylthio-1,3-dithiole-2-thione-5-thiolate using iodine as oxidant and obtained bis(4-benzoylthio-1,3-dithiole-2-thione)-5,5-disulfide, in two polymorphic forms (Comerlato et al., 2010). Recently the formation of a disulfide with a 4-(methylsulfanyl)-2H-1,3-dithiole-2-thione unit was reported from the reaction of a Cs complex with MCl 2 (M = Pt, Pd) by Kumar et al. (2017). Notably, such compounds predominantly constitute unanticipated side products and the focus of the respective characterization lies in crystallographic analyses with respect to solid-state intermolecular interactions and packing motifs. Only two analogous diselenide compounds with Se-Se moieties linking two 1,3-ene-dithiol-2-thione moieties are reported in the literature, albeit without crystallographic data (Cerrada et al., 1999;Takimiya et al., 2002). To date, no such compounds are known with 1,3-ene-dithiol-2-one moieties. A few examples are available for distantly related compounds in which cyclic alkenes are bridged by a diselenide moiety. Already in 1981, the synthesis, characterization and crystal structure of such a diselenide was described by Ruban et al.: bis{4-(2-thienyl)selenolo[3,4-b]thiophen-6-yl}diselenide was formed unexpectedly by the reaction of 2-[(triphenylphosphonio)methyl] thiophene chloride with sodium hydrogen selenite (Ruban et al., 1981). In 2000, Oilunkaniemi et al. published a procedure for the synthesis of thienyl-and furyl diselenide compounds, which was confirmed by respective crystal structures and selenium NMR spectra (Oilunkaniemi et al., 2000). Kumar & Nangia (2000) published the crystal structure of 2,2'-diselenobis(4,4-diphenylcyclo-hexa-2,5-dienone). In 2003, Thaler et al. synthesized cyclopentadienyl selenium compounds as multifunctional ligand systems with a varied number of selenium atoms in the Se n bridge (Thaler et al., 2003). Recently, the formation of a diselenide as a byproduct during the synthesis of heliannuol C (as confirmed by X-ray diffraction) was described by Biswas et al. (2017). The crystal structures of bis[4-methyl-1,3-dithiol-2one] disulfide and diselenide described in the current work are the first in which two 1,3-ene-dithiol-2-one moieties are linked by an S-S and an Se-Se bridge, respectively. For the latter, even the chemical structure is entirely unprecedented.

Synthesis and crystallization
Preparation of bis[4-methyl-1,3-dithiol-2-one] disulfide: This was undertaken by a modification of a published procedure (Dinsmore et al., 1998). 4-Methyl-1,3-dithiol-2-one (0.95 g, 7.2 mmol) and tributyltin chloride (2.92 ml, 8.63 mmol) in dry THF (10 ml) under nitrogen were cooled to 169 K (N 2 / MeOH:Et 2 O or dry ice/Et 2 O), and LDA (9.8 ml, 7.9 mmol, 10% solution in hexane) was added dropwise over 5 min. The mixture was allowed to stand for 35 min, warmed to ice-bath temperature and after a further 10 minutes quenched with a saturated aqueous solution of NH 4 Cl (around 20 ml). The organic phase was diluted with EtOAc, separated and the aqueous phase re-extracted with Et 2 O (2 Â 15 ml). The combined organic phases were washed with brine, dried and the solvent evaporated in vacuo to give a yellowish oil as crude product. This was purified by chromatography (silica gel), eluting with EtOAc/petroleum ether (40/60) 3:97 v/v to give 4methyl-5-tri-n-butylstannyl-1,3-dithiol-2-one as the major product. During purification, a yellowish oily fraction was isolated and subsequently stored at 253 K, forming large yellow crystals. Crystallographic evaluation of these crystals reveals the formation of the side product bis[4-methyl-1,3dithiol-2-one] disulfide.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The six methyl hydrogen atoms of each structure were included in calculated positions and treated as riding with C-H = 0.98 Å and U iso (H) = 1.5U eq (C).

Special details
Experimental. (X-RED32 and X-SHAPE; Stoe, 2010) 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
Experimental. (X-RED32 and X-SHAPE; Stoe, 2010) 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. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.