Crystal structure of 1-(4-methylphenyl)-3-(propan-2-ylideneamino)thiourea

The title twisted thiosemicarbazone molecule has, respectively, anti- and syn-dispositions of the p-tolyl-N—H and imino-N—H groups with respect to the central thione-S atom allowing for the formation of an intramolecular p-tolyl-N—H⋯N(imino) hydrogen bond. The presence of N—H⋯S hydrogen bonds lead to layers in the bc plane which are connected by methyl-C—H⋯π interactions.


Chemical context
The reaction between an alcohol or amine (primary or secondary) with N-alkyl-or N-aryl-isothiocyanides usually results in the formation of thiocarbamides. For example, in the case of reactions involving a monofunctional alcohol, the reaction proceeds in the following manner: R-OH + R 0 N C S ! ROC( S)N(H)R 0 (Ho et al., 2005). Often, reactions are facilitated by initially employing an alkali metal hydroxide as the base and later adding an acid, e.g. HCl (Ho et al., 2005). Such molecules are of interest as when deprotonated, they can function as effective thiolate ligands for phosphanegold(I) derivatives, which display biological activity. For example, Ph 3 PAu[SC(O-alkyl) N(aryl)] compounds exhibit significant cytotoxicity against a variety of cancer cell lines and mechanistic studies show that they can kill cancer cells by initiating a variety of apoptotic pathways, both extrinsic and intrinsic (Yeo, Ooi et al., 2013;Ooi, Yeo et al., 2015). Related species, i.e. Ph 3 PAu[SC(O-alkyl) N(ptolyl)], exhibit potency against Gram-positive bacteria (Yeo, Sim et al., 2013). Over and above these considerations, systematic studies into the structural chemistry of these molecules, which have proven relatively easy to crystallize, have been of some interest in crystal engineering endeavours (Ho et al., 2006;Kuan et al., 2008). In the course of studies to increase the functionality of the thiocarbamide molecules, bipodal {1,4-[MeOC( S)N(H)] 2 C 6 H 4 } was successfully synthesized along with binuclear phosphanegold(I) complexes (Yeo, Khoo et al., 2015). Recent attempts at expanding this chemistry by using thiourea as an amine donor have been undertaken. As reported very recently, 1:2 reactions between thiourea and R 0 N C S resulted in the isolation of salts containing 1,2,3thiazole-based cations resulting from 1:1 cyclizations (Yeo, Tan et al., 2015). Herein, the product of an analogous reaction ISSN 2056-9890 involving a bifunctional amine, i.e. H 2 NNH 2 (hydrazine) with (p-tolyl)N C S, conducted in acetone solution, is described, namely the thiosemicarbazone, (I). Molecules related to (I) and especially their metal complexes continue to attract attention owing to potential biological activity (Dilworth & Hueting, 2012;Lukmantara et al., 2013;Su et al., 2013).

Structural commentary
The molecular structure of (I), Fig. 1, comprises three planar regions. The central NC( S)N chromophore (the r.m.s. deviation of the fitted atoms is 0.0020 Å ) has anti-and syn-dispositions of the N1-and N2-bound H atoms, respectively, with respect to the central thione-S1 atom. The N1bound H atom is syn to the imino-N3 atom allowing for the formation of a five-membered loop via an N1-HÁ Á ÁN3 hydrogen bond, Table 1. The central plane forms dihedral angles of 23.49 (4) with the propan-2-ylideneamino residue (N CMe 2 ; r.m.s. deviation for the C 3 N atoms = 0.0002 Å ) and 43.30 (5) with the p-tolyl ring. Overall, the molecule is twisted as quantified by the dihedral angle between the outer planes of 29.27 (8) .
Two P2 1 /c polymorphs have been reported for the parent compound, i.e. having a phenyl rather than a p-tolyl substituent (Jian et al., 2005;Venkatraman et al., 2005); the structure of (I) also crystallizes in the P2 1 /c space group. As revealed from the data collated in Table 2, there is a high degree of concordance in the key bond lengths and angles for the three molecules, as might be expected. However, there are some notable differences in the torsion-angle data as well as in the dihedral angles between the three least-squares planes discussed above, Table 2. From these and the overlay diagram shown in Fig. 2, it is apparent that the molecular structure of (I) more closely matches that observed in the polymorph reported by Venkatraman et al. (2005) rather than that described by Jian et al. (2005). This conclusion is also vindicated in the unit cell data, i.e. a = 12.225 (3), b = 7.618 (2), c = 11.639 (3) Å , = 102.660 (4) reported for the former (Venkatraman et al., 2005).

NMR invesitgations
The conformation of (I) was also investigated in CDCl 3 solution by NMR methods. Assignments were made with the aid of the interpretative program, Chemdraw Ultra The molecular structure of (I) showing displacement ellipsoids at the 70% probability level. Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
Overlay diagram of the molecules in (I), red image, and (II), forms a (green) and b (blue). The molecules have been overlapped so that the central NC( S)N chromophores are coincident. 1 H and 13 C{ 1 H} resonances for the methyl groups of the propan-2-ylideneamino residue, it appears that the (propan-2ylideneamino)thiourea residue has a locked configuration, consistent with the persistence of the intramolecular N1-HÁ Á ÁN3 hydrogen bond in CDCl 3 solution.

Supramolecular features
In the crystal, N-HÁ Á ÁS and C-HÁ Á Á interactions provide identifiable points of contact between molecules; these interactions are quantified in Table 1. Centrosymmetrically related molecules are connected by pairs of amide-N2-HÁ Á ÁS1 hydrogen bonds, forming eight-membered thioamide {Á Á ÁHNCS} 2 synthons. These are connected into supramolecular layers in the bc plane by amide-N1-HÁ Á ÁS1 hydrogen bonds so that the S1 atom accepts two hydrogen bonds, Fig. 3. The p-tolyl groups protrude to either side of each layer and inter-digitate along the a axis with adjacent layers allowing for the formation of methyl-C8-HÁ Á Á(C2-C7) interactions, thereby consolidating the three-dimensional architecture, Fig. 4.

Analysis of the Hirshfeld surfaces
The crystal packing was further investigated by an analysis of the Hirshfeld surface (Spackman & Jayatilaka, 2009) employing CrystalExplorer (Wolff et al., 2012). Fingerprint plots (Rohl et al., 2008) were calculated, as were the electrostatic potentials using TONTO (Spackman et al., 2008;Jayatilaka et al., 2005)  Supramolecular layer in the bc plane in the crystal packing of (I).

Figure 4
A view of the unit cell contents of (I) shown in projection down the b axis. Supramolecular layers, illustrated in Fig. 3, are linked via C-HÁ Á Á interactions, shown as purple dashed lines, leading to a three-dimensional architecture.

Figure 5
Views of the Hirshfeld surface for (I): (a) and (b) mapped over d norm , and (c) mapped over the calculated electrostatic potential.
Two views of the Hirshfeld surface mapped over d norm are shown in Fig. 5a and b. The deep-red depressions at the S1 and N2 atoms (Fig. 5a) confirm their role as an acceptor and donor in the hydrogen-bonding scheme, respectively. This is also evident from the dark-red and blue regions, respectively, on the Hirshfeld surface mapped over the calculated electrostatic potential (Fig. 5c). The diminutive red spots near S1 and N1 (Fig. 5b) indicate their involvement in the intermolecular N-HÁ Á ÁS hydrogen bond.
The overall two-dimensional fingerprint plot (Fig. 6a) and those delineated into HÁ Á ÁH, SÁ Á ÁH/HÁ Á ÁS, NÁ Á ÁH/HÁ Á ÁN and CÁ Á ÁH/HÁ Á ÁC HÁ Á ÁH (Fig. 6b-d, respectively) interactions operating in the crystal structure of (I) are illustrated in Fig. 6; the relative contributions are summarized in Table 3. The prominent pair of sharp spikes of equal length (d e + d i = 2.45 Å ; Fig. 6b) with a 15.2% contribution due to SÁ Á ÁH/HÁ Á ÁS contacts to the Hirshfeld surfaces also suggest the presence of these interactions in the crystal packing. The light-red region near N3 (Fig. 5a) and diminutive red spot near N1-H (Fig. 5b) are consistent with relatively smaller contributions from NÁ Á ÁH/HÁ Á ÁN contacts, i.e. 2.5 and 3.0%, respectively, and are indicative of the weak intramolecular hydrogen bond. The strength of such an interaction can be visualized from the 2D fingerprint plot corresponding to NÁ Á ÁH/ HÁ Á ÁN contacts (Fig. 6c). The bright-orange spot in the surface mapped with d e (within a red circle in Fig. 7) about the aryl ring and a lightblue region around the tolyl-hydrogen atom, H8C (Fig. 7), suggest a contribution from the C-HÁ Á Á interaction (Table 1). This is also evident through distinct pair of 'wings' in the fingerprint plot corresponding to CÁ Á ÁH/HÁ Á ÁC contacts (Fig. 6d). The wing at the top, left belongs to C-H donors, while that at the bottom, right corresponds to the surface around -acceptors with 11.3 and 7.8% contribution from CÁ Á ÁH and HÁ Á ÁC contacts, respectively. The HÁ Á ÁH contacts reflected in the middle of scattered points in Fig. 6e     View of the Hirshfeld surface for (I) mapped over d e .
the most significant contribution, i.e. 57.0%, to the Hirshfeld surface arising from a side-ways approach. The small, flat segments delineated by the blue outline in the surface mapped with curvedness (Fig. 8) and the small (i.e. 0.7%) contribution from CÁ Á ÁC contacts to the surface indicates the absence of stacking interactions in the structure.

Database survey
According to a search of the Cambridge Structural Database (Groom & Allen, 2014), there are no direct analogues of (I), either in the coordinated or uncoordinated form. As mentioned in the Structural commentary, the parent compound has been characterized in two polymorphic forms (Jian et al., 2005;Venkatraman et al., 2005). The parent compound, LH, has also been observed to coordinate metal centres. Thus, monodentate coordination via the thione-S atom was observed in a neutral complex [ZnCl 2 (LH) 2 ] (Bel'skii et al., 1987). By contrast, a chelating mode via thione-S and imino-N atoms was observed in each of the charged complexes [CoBr(LH) 2 ]Br (Dessy et al., 1978) and [( 6 -pcymene)RuCl(LH)]Cl (Su et al., 2013). The most closely related structure having the p-tolyl substituent but variations at the imino-N atom is one where one methyl group has been substituted by a phenyl (Zhang et al., 2011). This is also a twisted molecule with the dihedral angle between the p-tolyl and NC 3 residues being 65.44 (7) .

Synthesis and crystallization
To p-tolyl isothiocyanate (Sigma-Aldrich; 10 mmol, 1.49 g) in acetone (20 ml) was added hydrazine monohydrate (Sigma-Aldrich; 10 mmol, 0.76 ml). The resulting mixture was stirred for 4 h at room temperature. Both chloroform (20 ml) and acetonitrile (20 ml) were then added, and the resulting mixture left for slow evaporation. Light-brown crystals were obtained after 2 weeks. Yield: 2.012 g (91%

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. Carbon-bound H-atoms were placed in calculated positions (C-H = 0.95-0.98 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 N-bound H atoms were located in a difference Fourier map but were refined with a distance restraint of N-H = 0.88AE0.01 Å , and with U iso (H) set to 1.2U eq (N).

1-(4-Methylphenyl)-3-(propan-2-ylideneamino)thiourea
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.