Crystal structure of tetraisobutylthiuram disulfide

The crystal structure of tetraisobutylthiuram disulfide reveals a −85.81 (1)° C—S—C—S torsion angle and multiple intra- and intermolecular S⋯C—H close contacts.


Chemical context
,N 0 -Tetraalkylthioperoxydicarbonic diamides, commonly called tetrathiuram disulfides, comprise a class of organosulfur compounds with applications that are both diverse and long-standing. Tetramethylthiuram disulfide, known by the commercial name thiram, is broadly useful both as a fungicide (Sharma et al., 2003) and as a repellent against animals that feed upon seedling trees (Radwan, 1969). In industry, thiram and related tetraalkylthiuram disulfides find application as vulcanizing agents in the production of synthetic rubber (Datta & Ingham, 2001;Ignatz-Hoover & To, 2016). Tetraethylthiuram disulfide, under the trade name disulfiram, is used for the treatment of chronic alcoholism because of its inhibitory effect upon liver alcohol dehydrogenase (Mutschler et al., 2016). More recently, it has received scrutiny for its ability to sensitize cancer cells to radiotherapy and to the effects of anticancer drugs (Jiao et al., 2016) as well as for its bactericidal action against drug-resistant Mycobacterium tuberculosis (Horita et al., 2012). Tetraalkylthiuram disulfides function both as chelating ligands themselves (Chieh, 1977;Chieh, 1978;Thirumaran et al., 2000;Saravanan et al., 2005;Prakasam et al., 2009) and as precursors to dithiocarbamate ligands, which are used in the coordination chemistry of both the transition metals (Hogarth, 2005) and main group elements (Heard, 2005).
In the course of some studies of diisobutyldithiocarbamate coordination complexes of molybdenum, we have noted a report describing an 1 H NMR spectrum of [Ni(S 2 CN i Bu 2 ) 2 ] that was more complex than anticipated, even considering the hindered rotation about the À S 2 -CN i Bu 2 bond (Raston & White, 1976). This complexity was attributed to intraligand SÁ Á ÁH interactions involving the tertiary hydrogen of the ISSN 2056-9890 isobutyl group. Although the room temperature 1 H NMR spectrum of N,N,N 0 ,N 0 -tetrakis(2-methylpropyl)thioperoxydicarbonic diamide (tetraisobutylthiuram disulfide) itself does not show evidence of such intramolecular interaction, several recent studies of tetrathiuram disulfides have suggested such interactions in the crystalline state (Raya et al., 2005;Srinivasan et al., 2012;Nath et al., 2016). This possibility of similar weak interaction(s) in the crystal structure of tetraisobutylthiuram disulfide has motivated a determination of its structure by X-ray diffraction, reported herein.

Structural commentary
Tetraisobutylthiuram disulfide crystallizes upon a general position in P1 but has pseudo-C 2 symmetry across the disulfide bond, strict C 2 symmetry being disrupted by conformational differences among the pendant isobutyl groups (Fig. 1a). Despite the lack of strict C 2 symmetry, tetraisobutylthiuram disulfide is nevertheless chiral. The image in Fig. 1a presents the molecule with a left-handed configuration to the core -H 2 CNC(S)S-SC(S)NCH 2 -portion. If Fig. 1a were to be viewed from above, along the pseudo C 2 axis that bisects the S3-S4 bond, the C1-S1 and C2-S2 thione bonds would project forward and backward, respectively, from the plane of the paper and thereby define a left-handed propeller. The right-handed counterpart is necessarily the other occupant of the unit cell, as required by the racemic space group. Among the structurally characterized thiuram disulfides, crystallographically imposed C 2 symmetry is also common (Fig. 3).
Multiple intramolecular SÁ Á ÁH-C contacts that are shorter than, or close to, the 2.92 Å sum of the van der Waals radii (Rowland & Taylor, 1996) for sulfur and hydrogen are calculated for the structure of tetraisobutylthiuram disulfide. Each of the four sulfur atoms on the molecule is a participant in such a close contact, as illustrated in Fig. 1b and shown in Table 1. Although weak individually, particularly since these D-HÁ Á ÁA angles are closer to 90 than to 180 (Table 1), these interactions may act cooperatively with packing forces to decide the specific molecular conformation that is adopted. Weak intermolecular SÁ Á ÁH-C contacts are also calculated for molecules that stack along the a axis of the cell (Fig. 2). While angles for these contacts are larger (145.6, 159.5 ), the DÁ Á ÁA separations are longer [3.834 (3), 3.810 (3) Å ]. The geometric parameters for both these intramolecular and intermolecular SÁ Á ÁC-H contacts fall within the range defined as consistent with a weak D-HÁ Á ÁA interaction (Desiraju & Steiner, 1999). These features of the molecular packing in the crystal structure of tetraisobutylthiuram disulfide suggest that the crystal structures of coordination complexes with the diisobutyldithiocarbamate ligand be considered for similar SÁ Á ÁH-C contacts and, importantly, that variable temperature 1 H NMR spectroscopy be used to assess the importance of any such interactions in solution.

Supramolecular features
Molecules of tetraisobutylthiuram disulfide are linked by C-HÁ Á ÁS hydrogen bonds (Table 1)   directed along the a axis of the cell, and parallel chains then align within the ab plane to form sheets (Fig. 2). Because the molecules within a single sheet are related, one from another, only by translations along a or b, they all have the same optical configuration. The sheets in the ab plane then stack along the c axis of the cell. The cell's inversion center resides within the center of the cell and relates molecules from neighboring sheets. Consequently, the sheets alternate in the handedness of the molecules from which they are comprised.
The C-S-S-C torsion angle () and the dihedral angle () between S 2 CN mean planes are closely comparable to values observed for the analogous features in most other tetrathiuram disulfides, as summarized in Fig. 3 Stacking of tetraisobutylthiuram disulfide molecules along the a axis of the unit cell, showing intermolecular SÁ Á ÁH-C close contacts. Displacement ellipsoids are represented at the 50% probability level. Parallel stacks fill in the ab plane to form two-dimensional sheets, as shown. (Symmetry operations: x + 1, y, z; x, y + 1, z.) Table 1 Hydrogen-bond geometry (Å , ). Summary of structurally characterized tetrathiuram disulfides, RR'NC(S)SSC(S)NRR'. thium disulfides that have been characterized structurally by X-ray diffraction (Fig. 3). For those which do not reside on an inversion center (Kumar et al., 1990;Są czewski et al., 2006)

Synthesis and crystallization
The synthesis procedure employed was that described by Kapanda et al., 2009

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms were added in calculated positions and refined with isotropic displacement parameters that were approximately 1.2 times (for -CH-and -CH 2 ) or 1.5 times (for -CH 3 ) those of the carbon atoms to which they were attached. The C-H distances assumed were 1.00, 0.99, and 0.98 Å for the -CH-, -CH 2 , and -CH 3 types of hydrogen atoms, respectively.

Special details
Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, collected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = -30.00 and 210.00°. The scan time was 60 sec/frame. 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.