Crystal structure of N-ethyl-2-(1,2,3,4-tetrahydronaphthalen-1-ylidene)hydrazinecarbothioamide

There are two molecules in the asymmetric unit of the title compound, one of them being disordered over the methyl group. The molecules are linked by weak H⋯S interactions into chains with graph-set motifs C(4) along [100] and and (10) rings. The Hirshfeld surface calculation suggests that the most important contribution for the crystal structure are the H⋯H interactions (64.20%).


Chemical context
The synthesis of thiosemicarbazone derivatives can be traced back to the early 1900 0 s (Freund & Schander, 1902). Initially, the chemically selective nucleophilic reaction with thiosemicarbazide, H 2 N-N(H)C( S)NH 2 , was employed for the identification and characterization of aldehydes and ketones, yielding the respective thiosemicarbazone. In the 1940s it was reported that in in vitro assays, the thiosemicarbazone turned out to be very effective against tuberculosis. In contrast, the related oxygen-containing semicarbazones did not shown biological activity in the same assays, so that the sulfur atom in the molecular structure is essential for Mycobacterium tuberculosis growth inhibition, a true milestone in the thiosemicarbazone pharmacological research (Domagk et al., 1946). Today, thiosemicarbazone chemistry is present across a wide range of scientific disciplines, especially inorganic coordination chemistry (Lobana et al., 2009) and medicinal chemistry. For example, the synthesis, the molecular docking calculation and the in vitro inhibition of Chikungunya virus replication by a thiosemicarbazone derivative was published in the past year (Mishra et al., 2016). Thus, the crystal structure determination of thiosemicarbazone derivatives is an intensive research field, especially for biological chemistry.

Structural commentary
The asymmetric unit shows two crystallographically independent molecules, one of them being disordered over the terminal methyl group. For the disordered molecule, the C25 atom ISSN 2056-9890 was fixed with restraints and had to be split over two positions with an occupancy ratio of 0.705 (5):0.295 (5) with A and B labels. As the orientations for this sp 3 -hybridized C atom are different, two possibilities for the disordered C26-atom locations are generated (Fig. 1).
The Hirshfeld surface analysis (Hirshfeld, 1977) of the crystal structure suggests that the contribution of the HÁ Á ÁH intermolecular interactions to the crystal packing amounts to 64.20%, the HÁ Á ÁS interactions amount to 12.60% and the HÁ Á ÁC interactions amount to 12.00%. Other important intermolecular contacts for the cohesion of the structure are (values given in %) are: HÁ Á ÁN = 5.50, CÁ Á ÁN = 3.60 and CÁ Á ÁC = 2.20. For the Hirshfeld surface analysis, the disorder over the molecule was not considered and the calculations were performed using the major occupancy component atoms. The graphical representation of the Hirshfeld surface (Fig. 3 Symmetry code: (i) x À 1; y; z.

Figure 1
The molecular structure of the title compound, with labeling and displacement ellipsoids drawn at the 40% probability level. The N3-H12Á Á ÁS2 and C9-H10Á Á ÁS2 interactions are drawn as dashed lines. Disordered atoms are shown with 30% transparency. The C25A/B atom is itself not disordered, but it was split using the same occupancy ratio as C26A and C26B.

Figure 2
Section of the crystal structure of the title compound, showing the N-HÁ Á ÁS and C-HÁ Á ÁS interactions. The graph-set motifs for the hydrogenbonding interactions in the crystal packing are C(4) and R 1 2 (10). The HÁ Á ÁS interactions are shown as dashed lines and connect the molecules into a chain along [100].
represented in magenta) suggests the locations of the strongest intermolecular contacts. The HÁ Á ÁH contribution for the crystal packing is shown as a Hirshfeld surface two-dimensional fingerprint plot with cyan dots (Wolff et al., 2012). The d e (y axis) and d i (x axis) values are the closest external and internal distances (in Å ) from given points on the Hirshfeld surface contacts (Fig. 4). As the most important contribution for the crystal packing is from the HÁ Á ÁH interactions, all other intermolecular interactions are relatively weak. As a consequence, the lengths of the HÁ Á ÁS contacts are close to or slightly above the sum of the van der Waals radii for H and S atoms (Bondi, 1964;Rowland & Taylor, 1996). Finally, the molecular packing shows a herringbone motif when viewed along [001] (Fig. 5).

Comparison with related structures
HÁ Á ÁH connections are the most important contribution for the crystal packing of 1-tetralone thiosemicarbazone derivatives; however, the HÁ Á ÁS contacts are relevant intermolecular interactions because of the possibility of forming hydrogen bonds. Therefore, D-HÁ Á ÁS hydrogen bonding is considered in the comparison of the title compound with related structures. In the crystal structure of 2-(1,2,3,4-tetrahydronaphthalen-1-ylidene)hydrazinecarbothioamide, the molecules are linked into chains by N-HÁ Á ÁS hydrogen bonds (HÁ Á ÁS distances = 2.45 and 2.71 Å ) and the HÁ Á ÁS contribution for the cohesion of the structure amounts to 19.20% ( Fig. 6a and   7a). This kind of arrangement, the one-dimensional hydrogenbonded polymer, is possible due to the unsubstituted amine, which increases the possibilities for intermolecular hydrogen  The Hirshfeld surface graphical representation (d norm ) for the asymmetric unit of the title compound. The surface regions with the strongest intermolecular interactions are shown in magenta. The disorder is not shown and the figure is simplified for clarity.

Figure 4
Hirshfeld surface two-dimensional fingerprint plot for the title compound showing the HÁ Á ÁH contacts in detail (cyan dots). The contribution of the HÁ Á ÁH interactions to the crystal packing amounts to 64.20%. The d e (y axis) and d i (x axis) values are the closest external and internal distances (in Å ) from given points on the Hirshfeld surface contacts. The disorder was not considered.
bonding (Oliveira et al., 2012). For the crystal structure of N-methyl-2-(1,2,3,4-tetrahydronaphthalen-1-ylidene)hydrazinecarbothioamide, one H atom of the amine group is substituted by one methyl group. The N-HÁ Á ÁS hydrogen bonds are weaker in comparison with the first structure (HÁ Á ÁS distances = 3.03 and 3.29 Å ), the HÁ Á ÁS contribution for the cohesion of the structure amounts to 15.80% and the dimensionality of the structure is preserved with molecules linked into chains ( Fig. 6b and 7b). The disorder over the molecules in the asymmetric unit was not considered and the calculations were performed using atoms of the major occupancy component (Oliveira et al., 2014a). Finally, for N-phenyl-2-(1,2,3,4-tetrahydronaphthalen-1-ylidene)hydrazinecarbothioamide, the molecules are also linked by N-HÁ Á ÁS hydrogen bonds, but not into hydrogen-bonded polymers (HÁ Á ÁS distance = 2.70 Å ). The phenyl rings linked to the amino groups change the molecular arrangement due to steric effects: the molecules build dimers and the HÁ Á ÁS contribution to the crystal packing amounts to 13.00% ( Fig. 6c and 7c) (Oliveira et al., 2014b). For the 1-tetralone 4-ethylthiosemicarbazone reported here, the HÁ Á ÁS contribution for the molecular cohesion on the crystal structure amounts to 12.60% (Fig. 7d). Thus, there is a relationship between the molecular assembly, the geometry of the HÁ Á ÁS interactions and their contribution to the crystal structures (Hirshfeld, 1977 andWolff et al., 2012).

Synthesis and crystallization
The starting materials are commercially available and were used without further purification. The synthesis of the title compound was adapted from a previously reported procedure (Freund & Schander, 1902). In a hydrochloric acid catalysed reaction, a mixture of 1-tetralone (10 mmol) and 4-ethyl-3thiosemicarbazide (10 mmol) in ethanol (80 mL) was stirred and refluxed for 4 h. After cooling and filtering, a pale-yellow solid was obtained. Colourless crystals were grown in tetrahydrofuran by slow evaporation of the solvent.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. One of the two independent molecules exhibits disorder of the methyl group. Although the secondary C atom of the ethyl substituent is not itself disordered, it was split using the same occupancy ratio as the terminal C atom to account for the different orientations of the two hydrogen atoms for the two disordered parts. The C25A and C25B atoms share the same site (EXYZ and EADP commands) and two positions will be possible for the terminal CH 3 -group. The C25 and C26 atoms were fixed with restraints (SADI command) and had to be split over two positions. The occupancy factor for C25A and C26A is 0.705 (5) and for C25B and C26B it is 0.295 (5). H atoms were located in difference maps but were positioned with idealized geometry and were refined with isotropic displacement parameters using a riding model (HFIX command) with U iso (H) =   Hirshfeld surface two-dimensional fingerprint plots for the crystal structures of (a) 1-tetralone thiosemicarbazone, (b) 1-tetralone 4methylthiosemicarbazone, (c) 1-tetralone 4-phenyllthiosemicarbazone and (d) 1-tetralone 4-ethylthiosemicarbazone showing the HÁ Á ÁS contacts in detail (cyan dots). The HÁ Á ÁS interactions contributions to the molecular cohesion on the crystal structures amount to 19.20, 15.80, 13.00 and 12.60%, respectively.

Acknowledgements
We gratefully acknowledge the financial support by the State of North Rhine-Westphalia, Germany. ABO is an associate researcher in the project 'Dinitrosyl complexes containing thiol and/or thiosemicarbazone: synthesis, characterization and treatment against cancer', founded by FAPESP, Proc. 2015/12098-0, and acknowledges Professor José C. M. Pereira (UNESP, Brazil) for his support. BRSF thanks CNPq for the award of a PIBIC scholarship and RLF thanks the CAPES foundation for the PhD scholarship.   N-ethyl-2-(1,2,3,4-tetrahydronaphthalen-1-yl-

Data collection
Nonius KappaCCD area detector diffractometer Radiation source: fine-focus sealed tube, Nonius Kappa CCD Graphite monochromator Detector resolution: 9 pixels mm -1 CCD rotation images, thick slices scans Absorption correction: multi-scan (Blessing, 1995)  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.48 e Å −3 Δρ min = −0.41 e Å −3 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. 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 > 2sigma(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.