Synthesis, crystal structure and Hirshfeld analysis of N-ethyl-2-{3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-ylidene}hydrazinecarbothioamide

The synthesis, crystal structure and Hirshfeld analysis of cis-jasmone 4-ethylthiosemicarbazone are reported. The crystallographically independent molecule shows disorder over the jasmone carbon chain and, in the crystal, the molecules are linked by H⋯S and H⋯N interactions into mono-periodic hydrogen-bonded ribbons parallel to the b-axis.

The title compound (C 14 H 23 N 3 S, common name: cis-jasmone 4-ethylthiosemicarbazone) was synthesized by the equimolar reaction of cis-jasmone and 4-ethylthiosemicarbazide in ethanol facilitated by acid catalysis.There is one crystallographically independent molecule in the asymmetric unit, which shows disorder of the terminal ethyl group of the jasmone carbon chain [site-occupancy ratio = 0.911 (5):0.089( 5)].The thiosemicarbazone entity [N-N-C( S)-N] is approximately planar, with the maximum deviation of the mean plane through the N/N/C/S/N atoms being 0.0331 (8) A ˚, while the maximum deviation of the mean plane through the five-membered ring of the jasmone fragment amounts to À 0.0337 (8) A ˚.The dihedral angle between the two planes is 4.98 (7) � .The molecule is not planar due to this structural feature and the sp 3 -hybridized atoms of the jasmone carbon chain.Additionally, one H� � �N intramolecular interaction is observed, with graph-set motif S(5).In the crystal, the molecules are connected through pairs of H� � �S interactions with R 2 2 (8) and R 2 1 (7) graph-set motifs into centrosymmetric dimers.The dimers are further connected by H� � �N interactions with graph-set motif R 2 2 (12), which are related by an inversion centre, forming a mono-periodic hydrogen-bonded ribbon parallel to the b-axis.The crystal structure and the supramolecular assembly of the title compound are compared with four known cis-jasmone thiosemicarbazone derivatives (two crystalline modifications of the non-substituted form, the 4-methyl and the 4-phenyl derivatives).A Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are from H� � �H (70.7%),H� � �S/S� � �H (13.5%),H� � �C/C� � �H (8.8%), and H� � �N/N� � �H (6.6%) interfaces (only the disordered atoms with the highest s.o.f. were considered for the evaluation).

Chemical context
Thiosemicarbazones [R 1 R 2 C N-N(H)C( S)NR 3 R 4 ] can be readily prepared through a well-known condensation reaction between a ketone or an aldehyde (R 1 R 2 C O) and a thiosemicarbazide derivative [H 2 N-N(H)C( S)NR 3 R 4 ] (Freund & Schander, 1902).Due to the structural diversity of the educts, a huge number of thiosemicarbazone derivatives (TSC) can be synthesized for numerous applications across a wide range of scientific disciplines, such as coordination chemistry, medicinal chemistry and materials science.These three main approaches are interconnected, as demonstrated by Farias et al. (2021) in a report concerning the synthesis, in vitro and in silico evaluations of the antitumor activities of two thiosemicarbazone Ni II complexes, which were considered materials with biological properties.The coordination chemistry of thiosemicarbazone derivatives was addressed in a review by Lobana et al. (2009), illustrating the chemical bonding of TSCs with metal centres of different Lewis acidity, the coordination modes and geometries, and some biological and analytical applications.
Several thiosemicarbazone derivatives have biological properties either as metal complexes or as non-coordinated molecules.For examples of thiosemicarbazone complexes with biological activity, see: Gupta et al. (2022); Khan et al. (2022);Monsur Showkot Hossain et al. (2023); Parrilha et al. (2022), which covers compounds for chemotherapy and medical diagnostic imaging combined, also referred to as theranostics, and Singh et al. (2023).For a review of TSC complexes in the inhibition of topoisomerases, which are biological targets of prime importance in cancer research, see: Jiang et al. (2023).For examples of the biological activity of non-coordinated thiosemicarbazone derivatives, see: Fatondji et al. (2013), which shows a small chemical library with 35 derivatives with trypanocidal activity against the Trypanosoma brucei brucei parasite, and for a review on tyrosinase inhibitory activity, which is another important biological target, see: Hałdys & Latajka (2019).The non-coordinated TSCs are also mentioned in a review on tyrosinase inhibition by Zolghadri et al. (2019).In addition, thiosemicarbazone derivatives have been studied for the treatment of Parkinson's disease (Mathew et al., 2021), microbial growth inhibition (D' Agostino et al., 2022), anti-inflammatory pathologies (Kanso et al., 2021) and antifungal activity (Bajaj et al., 2021).Specifically, in the context of this work, the parent cis-jasmone thiosemicarbazone derivative has shown fungistatic biological activity as a free molecule (Jamiołkowska et al., 2022) and also as a Cu II complex (Orsoni et al., 2020).
In materials science, thiosemicarbazone complexes are employed as single-source educts for the synthesis of nanostructured materials, e.g., CdS nanocrystals (Masikane et al., 2019) and nanostructured CuFeS 2 , which is being used as an electrode material for supercapacitors (Ansari et al., 2022).Non-coordinated thiosemicarbazones have been used to functionalize metal-organic frameworks (MOFs), such as zeolitic imidazolate frameworks (mainly, ZIF-8), for the removal of Hg II from aqueous solutions at room temperature and neutral pH (Jaafar et al., 2021).TSC derivatives have also been studied as corrosion inhibitors for metals and alloys.For the respective theoretical approach, see: Silva & Martı ´nez-Huitle (2021).Additionally, thiosemicarbazone derivatives have turned out to be useful in several fields of analytical chemistry, including calorimetry, fluorimetry and electrochemical sensors, e.g., in the detection of anions and metallic cations (O ¨zbek & Berkel, 2023).
In this context and as a contribution to the TSC chemistry, we report here the synthesis, crystal structure and Hirshfeld analysis of cis-jasmone 4-ethylthiosemicarbazone.

Supramolecular features
In the crystal, the molecules are connected through H� � �S and H� � �N interactions, forming rings of graph-set motifs R 2 2 (8), R 1 2 (7) and R 2 2 (12) for the C 2 H 2 N 2 S 2 , C 2 H 2 N 2 S and C 4 H 2 N 6 entities, respectively (Fig. 2).The S1 and N1 atoms act as double hydrogen-bond acceptors, where the N1 atoms play an important role in the supramolecular arrangement of the molecules.Firstly, the molecules are connected into centrosymmetric dimers through C2-H2A� � �S1 i and N2-H2� � �S1 i intermolecular interactions [symmetry code: (i) À x + 1, À y, À z + 1], as has also been observed in other cis-jasmone thiosemicarbazone derivatives (Oliveira et al., 2023a(Oliveira et al., , 2024)).These centrosymmetric dimers, in which rings of graph-set motif R 2 2 (8) and R 1 2 ( 7) are present, have their centres of gravity located in the centre of the ac planes.In addition, the dimers are further connected by C13-H13B� � �N1 ii intermolecular interactions [symmetry code: where rings of graph-set motif R 2 2 (12) are observed (Fig. 2, Table 1).The centre of gravity of the centrosymmetric C 4 H 2 N 6 ring lies at an inversion centre of the cell and thus, the molecules are linked into a mono-periodic hydrogen-bonded ribbon parallel to the b-axis.(Fig. 3).
The Hirshfeld surface analysis (Hirshfeld, 1977), the graphical representations and the two-dimensional Hirshfeld surface fingerprint plots (HSFP) were calculated with the Crystal Explorer software (Wolff et al., 2012) and only the atoms with the higher s.o.f. were taken into account.The Hirshfeld surface analysis of the title compound suggests that the most relevant intermolecular interactions for the crystal packing are H� � �H (70.7%),H� � �S/S� � �H (13.5%),H� � �C/ C� � �H (8.8%) and H � � �N/N� � �H (6.4%).The graphical representation of the Hirshfeld surface (d norm ) is given in a figure with transparency and using the ball-and-stick model.Locations of the strongest intermolecular contacts, i.e, the regions around the H2, H2A and S1 atoms are indicated in red (Fig. 4).These atoms are those involved in the H� � �S interactions shown in previous figures (Figs. 2 and 3).The contributions to the crystal cohesion are represented as twodimensional Hirshfeld surface fingerprint plots (HSFP) with coloured 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 contacts (in A ˚).

Database survey
To the best of our knowledge and from using database tools such as the Cambridge Structural Database (CSD, accessed via WebCSD on March 15, 2024; Groom et al., 2016), there are

Figure 2
Crystal structure section of the title compound showing the intermolecular hydrogen-bonding interactions as dashed lines.The molecules are linked via pairs of C2-H2A� � �S1 i , N-H2� � �S1 i and C13-H13B-N1 ii interactions with graph-set motifs R 2 2 (8), R 1 2 (7) and R 2 2 (12).[Symmetry codes:  four crystal structures of cis-jasmone thiosemicarbazone derivatives reported in the literature: the �-crystalline modification of cis-jasmone thiosemicarbazone, a-JTSC (refcode ZAJRUB; Orsoni et al., 2020), the �-crystalline modification, b-JTSC (ZAJRUB01; Oliveira et al., 2023b), cis-jasmone 4methylthiosemicarbazone, JMTSC (JOFYOW; Oliveira et al., 2024), cis-jasmone 4-phenylthiosemicarbazone, JPTSC (QIVYIH; Oliveira et al., 2023a), with cis-jasmone 4-ethylthiosemicarbazone, JETSC (this work) being the fifth.For the Hirshfeld analysis comparison, of the a-JTSC and the b-JTSC crystalline modifications, only b-JTSC was considered and will be designated in the following merely as JTSC.Fig. 6 provides the chemical structures of JTSC, JMTSC, JETSC and JPTSC.The Hirshfeld surface fingerprint signatures of the TSC derivatives are drawn as two-dimensional plots (HSFP) and the most relevant contribution for the crystal packing, the H� � �H intermolecular interactions, are highlighted (coloured) (Fig. 7).Their contributions for the crystal cohesion are 67.8% for JTSC, 70.6% for JMTSC, 70.7% for the title compound, JETSC, and 65.3% for JPTSC.It might be argued that the methyl and ethyl derivatives show more C-H entities for H� � �H intermolecular interactions in comparison to the nonsubstituted JTSC, and less steric hindrance than the phenyl derivative JPTSC.These structural features would explain the higher values of the H� � �H contributions to the crystal packing for JMTSC and JETSC, and the lower contributions for JTSC and JPTSC.In addition, the H� � �N/N� � �H contacts,   which are important for the supramolecular arrangement of JETSC (this work) are clearly represented in the HSFP signature of the crystal structure and do not appear in the same way in the signature of the related compounds (Fig. 8).
Although the contributions of the H� � �N/N� � �H contacts to the crystal packing for all the jasmone thiosemicarbazone derivatives are very similar in value, within a range of 4.9% to 6.4%, the H� � �N intermolecular interactions are of major importance for the molecular assembly of JETSC, as shown in Figs. 2 and 3.The influence of the substituent at the terminal N atom on the supramolecular assembly in the crystal structures of jasmone TSC derivatives is shown in Figs. 9 and 10.For the non-substituted �-and �-crystalline modifications of cisjasmone thiosemicarbazone, a-JTSC (Orsoni et al., 2020) and b-JTSC (Oliveira et al., 2023b), the molecules are connected via pairs of H� � �S interactions into mono-periodic hydrogenbonded ribbons.The crystal structure of a-JTSC shows three crystallographically independent molecules in the asymmetric unit.The molecules are linked by H� � �S interactions with graph-set motif R 2 2 (8) along [100] into two independent onedimensional hydrogen-bonded polymers (Fig. 9a).For b-JTSC, with one crystallographically independent molecule in the asymmetric unit, the molecules are connected by H� � �S interactions with graph-set motifs R 2 2 (8) and R 1 2 (7) into monoperiodic hydrogen-bonded ribbons along [010] (Fig. 9b).For the supramolecular assembly of cis-jasmone 4-methylthio-semicarbazone, JMTSC, (Oliveira et al., 2024) and of cisjasmone 4-phenylthiosemicarbazone, JPTSC, (Oliveira et al., 2023a), a structural similarity can be observed.In the crystal, the molecules are linked into centrosymmetric dimers by pairs of H� � �S interactions, in which rings of graph-set motifs R 2 2 (8) and R 1 2 (7) are present.As a result of the steric hindrance of the methyl and phenyl groups, respectively, the dimers are assembled as discrete units and only weak intermolecular interactions, viz., London dispersion forces can be assumed (Fig. 10a,b).The C-H� � �N intermolecular interactions observed in the crystal structure of the title compound, which cause the increase of the supramolecular dimensionality, are not observed in any of the four crystal structures of closely related molecules mentioned above.(a) Section of the molecular arrangement of a-JTSC (Orsoni et al., 2020).The three crystallographically independent molecules are A-, B-, and Clabelled.They are linked by pairs of N-H� � �S interactions, with rings of graph-set motif R 2 2 (8), into two independent mono-periodic hydrogenbonded ribbons along [100].[Symmetry codes: (i) x + 1, y, z; (ii) x À 1, y, z; (iii) À x + 1, À y, À z + 1; (iv) À x, À y, À z + 1.] (b) Section of the molecular arrangement of b-JTSC (Oliveira et al., 2023b).

Synthesis and crystallization
The starting materials are commercially available and were used without further purification.The synthesis of the cisjasmone 4-ethylthiosemicarbazone derivative was adapted from previously reported procedures (Freund & Schander, 1902;Oliveira et al., 2024;Orsoni et al., 2020).cis-Jasmone was dissolved in ethanol under magnetic stirring at room temperature (8 mmol, 1.3139 g, in 50 mL).A solution of 4ethylthiosemicarbazide in ethanol (8 mmol, 0.9535 g, in 50 mL) was prepared under the same conditions.The solutions were combined, the HCl catalyst was added (1 mL, 1 M), and the final mixture was refluxed under magnetic stirring for 8 h.After cooling, the precipitated product was filtered off and washed with cold ethanol.Yield = 0.7431 g (35%).Colourless single crystals suitable for X-ray diffraction were obtained from tetrahydrofuran by slow evaporation of the solvent at room temperature.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2.There is one crystallographically independent molecule in the asymmetric unit of the title compound, which shows disorder over the chain of the cisjasmone fragment, viz., the C9 and C10 atoms [Fig.1; siteoccupancy ratio = 0.911 (5):0.089( 5)].The H atoms were refined freely, with exception of those bonded to C9B and C10B.These constrained H atoms were located in a difference-Fourier map, but were positioned with idealized geometry and refined isotropically using a riding model.For the H atoms attached to atom C9B with U iso (H) = 1.2 U eq (C), the C-H bonds were set to 0.97 A ˚.For the C10B atom, the methyl H atoms were allowed to rotate but not to tip to best fit the experimental electron density, with U iso (H) = 1.5 U eq (C), and the C-H bonds were set to 0.96 A ˚. H atoms treated by a mixture of independent and constrained refinement �� max , �� min (e A ˚À 3 ) 0.29, À 0.21 Computer programs: COLLECT (Nonius, 1998), HKL, DENZO and SCALEPACK (Otwinowski & Minor, 1997), SIR92 (Altomare et al., 1994), SHELXL2018/3 (Sheldrick, 2015), DIAMOND (Brandenburg, 2006), CrystalExplorer (Wolff et al., 2012), WinGX (Farrugia, 2012), publCIF (Westrip, 2010) and enCIFer (Allen et al., 2004).

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 3
Figure 3 Crystal structure section of the title compound, showing the intermolecular hydrogen-bonded interactions as dashed lines.Disorder is not shown for clarity.The molecules are linked into mono-periodic hydrogenbonded ribbons parallel to the b-axis via pairs of N-H� � �S, C-H� � �S and C-H� � �N interactions with graph-set motifs R 2 2 (8), R 1 2 (7) and R 2 2 (12).

Figure 4
Figure 4 Hirshfeld surface graphical representation (d norm ) for the title compound.The surface is drawn with transparency, the molecules are drawn in ball and stick model and the disorder is not shown for clarity.The regions with strongest intermolecular interactions are shown in red.

Figure 5 The
Figure 5 The Hirshfeld surface two-dimensional fingerprint plot (HSFP) for the title compound, showing the contacts in detail (coloured).The major contributions of the interactions to the crystal cohesion amount to (a) H� � �H (70.7%),(b) H� � �S/S� � �H (13.5%),(c) H� � �C/C� � �H (8.8%) and (d) H� � �N/N� � �H (6.4%).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 contacts (in A ˚). Regarding the disorder, only the atoms with the highest s.o.f. were considered.

Figure 7 The
Figure 7The Hirshfeld surface two-dimensional fingerprint plot (HSFP) signatures for (a) JTSC(Oliveira et al., 2023b), (b) JMTSC(Oliveira et al., 2024), (c) JETSC (this work) and (d) JPTSC(Oliveira et al., 2023a).The major contributions for the crystal cohesion in all structures are the H� � �H intermolecular interactions, which amount to 67.8%, 70.6%, 70.7% and 65.3%, respectively, and are highlighted (coloured).The d i (xaxis) and the d e (y-axis) values are the closest internal and external distances from given points on the Hirshfeld surface contacts (in A ˚). Regarding the disorder, only the atoms with the highest s.o.f. were considered.

Figure 8 The
Figure 8The Hirshfeld surface two-dimensional fingerprint plot (HSFP) signatures for (a) JTSC(Oliveira et al., 2023b), (b) JMTSC(Oliveira et al., 2024), (c) JETSC (this work) and (d) JPTSC(Oliveira et al., 2023a), with the H� � �N/N� � �H contacts highlighted (coloured).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 contacts (in A ˚). Regarding the disorder, only the atoms with the highest s.o.f. were considered.

Table 2
Experimental details.