S-Benzyl 3-[1-(6-methylpyridin-2-yl)ethylidene]dithiocarbazate: crystal structure and Hirshfeld surface analysis

The title molecule has a approximately coplanar relationship between the methylidenehydrazinecarbodithioate (C2N2S2) core and substituted pyridyl ring but the former plane is nearly orthogonal to the thioester phenyl ring. Supramolecular layers in the bc plane sustained by C—H⋯S and C—H⋯π interactions feature in the crystal.


Chemical context
Dithiocarbazates are compounds that contain both nitrogen and sulfur donor atoms, which can react with ketones or aldehydes, via condensation, to yield Schiff bases. Different ligands can be obtained by introducing different organic substituents, which causes variation in their biological properties, although they may differ only slightly in their molecular structures (Ali et al., 1977;Tarafder et al., 2001Tarafder et al., , 2002. Interest in this class of compound remains high as studies have shown that they possess anti-cancer (Mirza et al., 2014), anti-bacterial (Bhat et al., 2018), anti-fungal (Nithya et al., 2017), anti-viral (Chew et al., 2004) and anti-inflammatory (Zangrando et al., 2015) properties. Pyridine derivatives have also been a subject of much interest since the 1930 0 s with the discovery of niacin for the treatment of dermatitis and dementia (Henry, 2004). 3-Aminopyridinecarbaldehyde thiosemicarbazone is another pyridine-containing compound that has shown promising activity in advanced leukemia patients in a clinical phase I evaluation (Karp et al., 2008). Although considerable work has been conducted on pyridine-derived Schiff bases and their biological activities, we report, as part of our research into the synthesis and characterization of pyridine-based Schiff bases and their metal complexes, the crystal structure and Hirshfeld surface analysis of a potentially tridentate Schiff base derived from the condensation of S-benzyldithiocarbazate with 2-acetyl-6-methyl pyridine.

Structural commentary
The molecular structure of (I), Fig. 1, comprises three distinct almost planar residues with the central methylidenehydrazinecarbodithioate, C 2 N 2 S 2 , chromophore [r.m.s. deviation = 0.0111 Å ] being flanked by the thioester-phenyl ring and the substituted pyridyl ring, forming dihedral angles of 71.67 (3) and 7.16 (7) , respectively, indicating nearly orthogonal and co-planar dispositions, respectively; the dihedral angle between the outer rings is 65.79 (4) . The configuration about the imine-C9 N2 bond [1.2924 (18) Å ] is Z, resulting in the hydrazine-N1-H hydrogen atom being directed towards the pyridyl-N3 atom, enabling the formation of an intermolecular amine-N1-HÁ Á ÁN3(pyridyl) hydrogen bond that closes an S(6) loop, Table 1. The pyridyl-methyl group is syn with the thione-S1 atom and at the same time is orientated to the opposite side of the molecule to the iminebound methyl group.

Figure 1
The molecular structure of (I), showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.

Analysis of the Hirshfeld surfaces
The Hirshfeld surfaces calculated for (I) were performed in accord with recent studies on an organic molecule (Tan et al., 2017) and serve to provide insight into the influence of different intermolecular interactions in the crystal. A very short (2.23 Å ) intra-layer HÁ Á ÁH contact between the phenyl-H4 and pyridyl-H15 atoms ( Table 2) is significant in the crystal of (I) and is viewed as the bright-red spots near these atoms on the Hirshfeld surface mapped over d norm in Fig. 3a (labelled as '1'). The presence of the weak intermolecular C-HÁ Á ÁS contact involving the phenyl-C8 and thione-S2 atoms is evident from the diminutive red spots near these atoms in Fig. 3 (labelled as '2'). The faint-red spots near the phenyl-H7 and -C8 atoms in Fig. 3b (labelled as '3') characterize the short surface CÁ Á ÁH/HÁ Á ÁC contacts and indicate the relative importance of this particular C-HÁ Á Á contact compared with the other two C-HÁ Á Á contacts summarized in Table 1. The most prominent interlayer contact appears to be a weak methyl-C16-HÁ Á ÁS1(ester) interaction ( Table 2). The donors and acceptors of intermolecular interactions are also represented with blue and red regions, respectively, corresponding to positive and negative electrostatic potentials on the Hirshfeld surface mapped over electrostatic potential in Fig. 4. The intermolecular C-HÁ Á Á contacts, involving donor atoms, and their reciprocal contacts, i.e. Á Á ÁH-C, containing -bond acceptors, on the Hirshfeld surface mapped with the shape-index property are illustrated in Fig Views of Hirshfeld surface mapped over d norm for (I): (a) in the range À0.120 to +1.541 au highlighting short interatomic HÁ Á ÁH contacts with yellow dashed lines and label '1' and (b) in the range À0.050 to +1.541 au highlighting short interatomic CÁ Á ÁH/HÁ Á ÁC contacts with black dashed lines and label '3'. Weak intermolecular C-HÁ Á ÁS/SÁ Á ÁH-C contacts are indicated by sky-blue dashed lines and label '2' in both (a) and (b).

Figure 4
Two views of the Hirshfeld surface mapped over the electrostatic potential for (I) in the range AE0.055 au. The red and blue regions represent negative and positive electrostatic potentials, respectively.  Table 2 Summary of short surface contacts (Å ) in (I).
Contact Distance Symmetry operation 3.05 -x, Ày, Àz different interatomic contacts to the Hirshfeld surface are summarized in Table 3. The single tip at d e + d i $ 2.0 Å near the vertex of the cone-shaped distribution of points in the fingerprint plot delineated into HÁ Á ÁH contacts (Fig. 6b) indicate the significant influence of the short interatomic phenyl-HÁ Á ÁH(pyridyl) contacts in the crystal mentioned above. The intermolecular C-HÁ Á Á interactions discussed earlier are characterized by short interatomic CÁ Á ÁH/HÁ Á ÁC contacts (Table 2) and their presence are indicated by the distribution of points around a pair of peaks at d e + d i $ 2.8 Å in Fig. 6c, and by the concave surfaces around the phenyl (C3-C8) and pyridyl (N3,C11-C15) rings on the Hirshfeld surface mapped over the electrostatic potential in Fig. 4. The intermolecular C8-H8Á Á ÁS2 contact in the crystal is characterized by the pair of forceps-like tips at d e + d i $ 2.8 Å in Fig. 6d. The interatomic NÁ Á ÁH/HÁ Á ÁN contacts do not represent directional interactions as the interatomic separations are greater than sum of their van der Waals radii as evident from Fig. 6e.
Similarly, the other surface contacts summarized in Table 3 have negligible effect on the packing.

Database survey
As mentioned in the Chemical context, there is sustained interest in this class of compound and this is reflected by the observation there are four closely related structures available for comparison, varying in the S-bound group and substitution in the 2-pyridyl ring. In common with (I), the derivative with the 4-methylbenzyl ester and with a methyl group in the 5-position of the pyridyl ring, a Z-configuration is noted about the imine bond allowing for the formation of an intramolecular hydrazine-N-HÁ Á ÁN(pyridyl) hydrogen bond (Ravoof et al., 2015). By contrast, the three remaining analogues, i.e. the methyl ester with no substitution in the pyridyl ring (Basha et al., 2012), benzyl ester/4-methylpyridyl and 4-methylbenzyl ester/4-methylpyridyl (Omar et al., 2014), an E-configuration is found about the imine bond, a disposition that allows for the formation of intermolecular thioamide-N-HÁ Á ÁS(thione) hydrogen bonds and eight-membered {Á Á ÁHNCS} 2 synthons. Two views of Hirshfeld surface mapped with shape-index properties for (I) highlighting (a) C-HÁ Á Á contacts and (b) their reciprocal i.e. Á Á ÁH-C contacts, with red and blue dotted lines, respectively, and labels '1'-'3'.

Synthesis and crystallization
All chemicals were of analytical grade and were used without any further purification. S-Benzyldithiocarbazate (SBDTC) was prepared according to the method published by Ali & Tarafder (1977). Potassium hydroxide (11.4 g, 0.2 mol) was dissolved in absolute ethanol (70 ml) and to this solution hydrazine hydrate (10 g, 0.2 mol) was added. The mixture was then cooled in an ice bath followed by the dropwise addition of carbon disulfide (15.2 g, 0.2 mol) with constant stirring over 1 h. The two layers that formed were then separated using a separating funnel. The brown organic lower layer was dissolved in 40% ethanol. Benzyl chloride (25 ml, 0.2 mol) was then added dropwise into the mixture with vigorous stirring. The white product that formed was filtered off, washed with cold ethanol and dried in a desiccator over anhydrous silica gel. Pure SBDTC was obtained by recrystallization using absolute ethanol as the solvent. Yield: 75%, m.p. 397-399 K. SBDTC (1.98 g, 0.01 mol) was subsequently dissolved in hot acetonitrile (100 ml) and added to an equimolar solution of 2-acetyl-6-methyl pyridine (1.35 g, 0.01 mol) in ethanol (25 ml). The mixture was then heated on a water bath until the volume reduced to half. A yellow precipitate formed upon standing at room temperature for 1 h which was washed with cold ethanol. A small amount of product was dissolved in acetonitrile and left to stand for a week, after which yellow prisms suitable for single-crystal X-ray diffraction analysis formed. IR (cm À1 ): 2921 (N-H), 1560 (C N), 1055 (N-N), 881 (CSS).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. The carbon-bound H atoms were placed in calculated positions (C-H = 0.95-0.99 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2-1.5U eq (C). The nitrogen-bound H atom was located in a difference Fourier map, but was refined with a distance restraint of N-H = 0.88AE0.01 Å , and with U iso (H) set to 1.2U eq (N).

S-Benzyl 3-[1-(6-methylpyridin-2-yl)ethylidene]dithiocarbazate
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.