2-{1-[(6R,S)-3,5,5,6,8,8-Hexamethyl-5,6,7,8-tetrahydronaphthalen-2-yl]ethylidene}-N-methylhydrazinecarbothioamide

The synthesis, crystal structure and Hirshfeld analysis of (R,S)-fixolide 4-methylthiosemicarbazone is reported. The compound is disordered over the fixolide fragment and in the crystal, the molecules are linked by H⋯S interactions with graph-set motif C(4), forming mono-periodic hydrogen-bonded ribbons along [100].

The reaction between a racemic mixture of (R,S)-fixolide and 4-methylthiosemicarbazide in ethanol with a 1:1 stoichiometric ratio and catalysed with HCl, yielded the title compound, C 20 H 31 N 3 S [common name: (R,S)-fixolide 4-methylthiosemicarbazone].There is one crystallographically independent molecule in the asymmetric unit, which is disordered over the aliphatic ring [siteoccupancy ratio = 0.667 (13):0.333( 13)].The disorder includes the chiral C atom, the neighbouring methylene group and the methyl H atoms of the methyl group bonded to the chiral C atom.The maximum deviations from the mean plane through the disordered aliphatic ring amount to 0.328 (6) and À 0.334 (6) A ˚[r.m.s.d.= 0.2061 A ˚], and À 0.3677 (12) and 0.3380 (12) A ˚[r.m.s.d.= 0.2198 A ˚] for the two different sites.Both fragments show a half-chair conformation.Additionally, the N-N-C( S)-N entity is approximately planar, with the maximum deviation from the mean plane through the selected atoms being 0.0135 (18) A ˚[r.m.s.d.= 0.0100 A ˚].The molecule is not planar due to the dihedral angle between the thiosemicarbazone entity and the aromatic ring, which amounts to 51.8 (1) � , and due to the sp 3 -hybridized carbon atoms of the fixolide fragment.In the crystal, the molecules are connected by H� � �S interactions with graph-set motif C(4), forming a mono-periodic hydrogenbonded ribbon along [100].The Hirshfeld surface analysis suggests that the major contributions for the crystal cohesion are [(R,S)-isomers considered separately] H� � �H (75.7%),H� � �S/S� � �H (11.6%),H� � �C/C� � �H (8.3% and

Structure description
The thiosemicarbazone chemistry is essentially interdisciplinary and these molecules, characterized by the R 1 R 2 N-N(H)-C( S)-NR 3 R 4 functional group, play an important role in a wide range of scientific disciplines, including biochemistry, coordination chemistry and materials science.Originally, thiosemicarbazone derivatives were the major product of a condensation reaction employed in the organic chemistry for the detection of ketones and aldehydes, using thiosemicarbazide as analytical reagent (Freund & Schander, 1902).As a result of the huge structural diversity of ketones and aldehydes, a large number of thiosemicarbazone derivatives can be easily obtained for various applications.One of the earliest reports on the application of the thiosemicarbazones can be traced back to the middle of the 1940s, when these compounds were proved to be effective on Mycobacterium tuberculosis growth inhibition (Domagk et al., 1946).Until today, the biological activity of thiosemicarbazone derivatives remains one of the most important approaches for this chemistry.Thiosemicarbazone derivatives are well known for their biological properties, e.g., antifungal (Bajaj et al., 2021), antitumoural (Farias et al., 2021;Rocha et al., 2019;Siqueira et al., 2019) and anti-inflammatory pathologies (Kanso et al., 2021), to cite just a few examples.For instance, thiosemicarbazone coordination compounds also have applications in diagnostic medical imaging and theranostics (Dilworth & Hueting, 2012;Parrilha et al., 2022).In addition, thiosemicarbazone complexes are employed as single-molecule precursors in the synthesis of nanostructured materials through thermal decomposition techniques.Thus, Co II , Cd II and Zn II complexes are used for the synthesis of CoS and Co 9 S 8 (Pawar & Garje, 2015), CdS (Pawar et al., 2016) and ZnS (Palve & Garje, 2011) nanoparticles, respectively.For a review of the coordination chemistry of thiosemicarbazones, showing the different bonding modes with diverse metal centres and Lewis acidity, see: Lobana et al. (2009).Finally, thiosemicarbazone derivatives can act as organic corrosion inhibitors, e.g., as a layer of protection for carbon steel AISI 1020 in a hydrochloric acid medium (Goulart et al., 2013) and for a theoretical study of the corrosion inhibition concerning dimeric thiosemicarbazones, see: Silva & Martı ´nez-Huitle (2021).
As part of our interest in this chemistry, we report herein the synthesis, crystal structure and Hirshfeld analysis of the title (R,S)-fixolide 4-methylthiosemicarbazone compound.The molecular structure matches the asymmetric unit, which is disordered over the aliphatic ring, with the site-occupancy ratio being 0.667 (13):0.333(13) for the A-and B-labelled atoms, respectively (Fig. 1).A racemic mixture of fixolide was employed as starting material.As the disorder includes the C10 chiral centre, with C10A-H10A and C10B-HB bonds in opposite directions, (R)-and (S)-isomers are observed.The C9 atom was also split over two positions into C9A and C9B, with the same respective occupancy ratio.The C18 atom is itself not disordered, but the H atoms attached to the carbon atom of this methyl group were refined as disordered to get the best orientations for the C-H bonds, since it is bonded to the sp 3hybridized C10A and C10B atoms.The displacement ellipsoids for C16, C17, C19 and C20 are prolate-like, but no disorder was suggested by the data analysis.
Concerning the thiosemicarbazone entity, the torsion angles for the N3/N2/C2/N1 and the N3/N2/C2/S1 atom chains amount to 1.2 (4) and À 178.1 (2) � , respectively.The maximum deviation from the mean plane through the N3/N2/C2/S1/N1 atoms is 0.0135 (18) A ˚for N2 (r.m.s.d.= 0.0100 A ˚), thus, the fragment is approximately planar.The molecule of the title compound is not planar due to the sp 3 -hybridized C atoms of the apliphatic ring and due to the dihedral angle between the mean plane through the N3/N2/C2/S1/N1 atoms and the mean plane through the aromatic ring of the fixolide fragment, which amounts to 51.8 (1) � .
The Hirshfeld surface analysis (Hirshfeld, 1977), the graphical representations and the two-dimensional Hirshfeld surface fingerprint plots for the title compound were performed using CrystalExplorer (Wolff et al., 2012).The Hirshfeld surface analysis of the crystal structure indicates that the most relevant intermolecular interactions for crystal cohesion are H� � �H (75.7%),H� � �S/S� � �H (11.6%),H� � �C/ C� � �H (8.3% and H� � �N/N� � �H (4.4%).The graphics of the Hirshfeld surface of the title compound are represented with transparency in two opposite side-views and separate figures for clarity (Fig. 4).The locations of the strongest intermolecular contacts are indicated in red, i.e, the regions around the H1 and S1 atoms.These atoms are those involved in the H� � �S interactions shown in a previous figure (Fig. 2) and in Table 1.
Although the Hirshfeld surface graphical representation shows, in red, locations of intermolecular contacts involving H atoms attached to C atoms, no C-H� � �H-C intermolecular interactions can be assigned.The fixolide fragment is a nonpolar organic periphery and only weak intermolecular interactions, e.g., London dispersion forces, can be considered.The contribution of H� � �H intermolecular interactions in the supramolecular arrangement of crystal structures has been studied (Almeida et al., 2017), but this is not the focus of the present work.The crystal structure of the title compound is disordered, the H atoms were placed geometrically, the Rfactor amounts to 0.079 and no additional experiment for the intermolecular interactions was performed, so it is not recommended to assure such contacts here.Additionally, no short H� � �H intermolecular distances were observed.
The contributions to the crystal packing are shown as twodimensional Hirshfeld surface fingerprint plots with cyan dots (Fig. 5).The d i (x-axis) and the d e (y-axis) values are the closest internal and external distances from given points on the Hirshfeld surface (in A ˚).
To the best of our knowledge and from using database tools such as SciFinder    on November 18, 2023; Groom et al., 2016), this work represents the first report on the synthesis, crystal structure and Hirshfeld analysis of the fixolide 4-methylthiosemicarbazone molecule.Thus, two crystal structures with similarities to the title compound were selected for comparison.
The first selected example is the crystal structure of the tetralone 4-ethylthiosemicarbazone (Oliveira et al., 2017).There are two molecules with atoms in general positions forming the asymmetric unit, one of them being disordered over the ethyl fragment.In the crystal, the molecules are linked by H� � �S interactions along [100], with graph-set motif C( 4), and forming a mono-periodic hydrogen-bonded ribbon (Fig. 6), as observed to the title compound (Fig. 2).The tetralone entity consists of one aliphatic and one aromatic ring, and for the non-polar organic periphery are suggested weak intermolecular interactions only, since even �-� interactions are not present in the structure.
The second example is the crystal structure of a (R,S)fixolide carboxylic acid derivative (Kuhlich et al., 2010).For this structure, only one crystallographic independent molecule is observed in the asymmetric unit, which shows disorder over the aliphatic ring and two methyl groups (Fig. 7).The chiral centre is disordered, C10A and C10B, and two isomers are observed, namely the (R)-and (S)-forms.For the synthesis, a racemic mixture of fixolide was used as starting material.For the (R,S)-fixolide carboxylic acid derivative, the s.o.f.ratio amounts to 0.683 (4):0.317(4).The torsion angles of the C9/ C10A/C11A/C12 and the C9/C10B/C11B/C12 atom chains amount to À 67.0 (3) and 71.8 (6) � , respectively, being similar to the selected chains of the title compound (Table 2).
compound was adapted from previously reported procedures (Freund & Schander, 1902;Oliveira et al., 2017).A mixture of the racemic fixolide (5 mmol) and 4-methylthiosemicarbazide (5 mmol) in ethanol (80 ml), catalysed with HCl, was stirred and refluxed for 8 h.After cooling at room temperature, a colourless crystalline solid precipitated, was filtered off and washed with cold ethanol.The crystalline solid was dissolved in warm ethanol and single crystals suitable for X-ray diffraction were obtained by slow evaporation of the solvent at room temperature.The site-occupancy ratio of the disordered atoms refined to 0.667 (13):0.333(13).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3.The crystallographically independent molecule is disordered over the aliphatic ring (C9A, C9B, C10A and C10B) (Fig. 1).The s.o.f. for the A-labelled atoms amounts to 0.667 (13), while for the B-labelled atoms it is 0.333 (13).Although the displacement ellipsoids of C16, C17, C19 and C20 are prolate-like in comparison with the ellipsoids of other methyl groups, e.g., C1, C4, C15 and C18, no additional disorder was indicated by the data analysis.
The hydrogen atoms attached to carbon and nitrogen atoms were positioned with idealized geometry and constrained to ride on their parent atoms.To get the best orientations for the C-H bonds of the C18H 3 group, which is bonded to the C10A and C10B atoms, the methyl hydrogen atoms were split into two positions, located geometrically and refined using a riding model [U iso (H) = 1.5U eq (C); C-H bonds lengths set to 0.96 A ˚].The other methyl groups were allowed to rotate but not to tip to best fit the experimental electron density and the same C-H bond lengths value was set, also with U iso (H) = 1.5U eq (C).The U iso (H) = 1.2U eq (C) relation was employed for the other C-H bonds and, for the phenyl ring H atoms, the C-H bond lengths were set to 0.93 A ˚.For the disordered -CH 2 -fragment (C9A and C9B), the C-H bond-length value was set to 0.97 A ˚and for the disordered tertiary C atoms (C10A and C10B), the C-H bond lengths amount to 0.98 A ˚. Finally, the N-H bond lengths, with U iso (H) = 1.2U eq (N), were set to 0.86 A ˚.
data reports

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.

Figure 2
Figure 2 Graphical representation of the H� � �S intermolecular interactions for the title compound viewed along [010].The interactions are drawn as dashed lines, with graph-set motif C(4), and connect the molecules into a monoperiodic hydrogen-bonded ribbon along [100].Only the major occupied sites are drawn for clarity.[Symmetry codes: (i) x + 1, y, z; (ii) x À 1, y, z.] (Chemical Abstracts Service, 2023) and the Cambridge Structural Database (CSD, accessed via WebCSD data reports IUCrData (2023).8, x231020 Melo et al. � C 20 H 31 N 3 S 3 of 6

Figure 3
Figure 3 Section of the crystal packing of the title compound.The arrangement of the molecules shows a zigzag or a herringbone motif when viewed along [100].Only the major occupied sites are drawn for clarity.

Figure 4
Figure 4 Two opposite side-views in separate figures of the Hirshfeld surface graphical representation (d norm ) for the title compound.The surface is drawn with transparency and simplified for clarity.The regions with strongest intermolecular interactions are shown in red.(d norm range: À 0.142 to 1.510.)

4 of 6 Figure 5
Figure 5 The Hirshfeld surface two-dimensional fingerprint plot for the the title compound showing the (a) H� � �H (75.7%),(b) H� � �S/S� � �H (11.6%),(c) H� � �C/C� � �H (8.3%) and (d) H� � �N/N� � �H (4.4%) contacts in detail (cyan dots) and the contributions of the interactions for the crystal packing.The d i (x-axis) and the d e (y-axis) values are the closest internal and external distances from given points on the Hirshfeld surface (in A ˚).

Table 3
Experimental details.