Conversion of diarylchalcones into 4,5-dihydropyrazole-1-carbothioamides: molecular and supramolecular structures of two precursors and three products

1,3-Disubstituted chalcones have been converted into 3,5-disubstituted 4,5-dihydropyrazole-1-carbothioamides by reaction with thiosemicarbazide. Two isomorphous chalcone precursors form hydrogen-bonded sheets, while in two isomorphous reduced pyrazole products, hydrogen-bonded chains of rings are formed: in a third product, the molecules are linked into complex sheets.


Chemical context
Pyrazole derivatives exhibit a wide range of pharmacological activities, including analgesic (Badawey & El-Ashmawey, 1998), antibacterial (Zhang et al., 2017), anticancer (Koca et al., 2013) and anti-inflammatory (Vijesh et al., 2013) activity, and recent work on both the synthesis of pyrazole derivatives and their pharmacological activities has been reviewed recently (Karrouchi et al., 2018). With this background in mind, we have now employed three chalcones, compounds (I)-(III) as precursors for the synthesis of the corresponding 4,5-dihydropyrazole-1-carbothioamides, compounds (IV)-(VI), and we report here the molecular and supramolecular structures of two of the chalcone precursors, compounds (I) and (II), and of the three reduced pyrazole products (IV)-(VI): unfortunately, we have been unable to obtain satisfactory crystals of the chalcone (III). The chalcones were The molecular structure of compound (II) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 4
The molecular structure of compound (V) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 1
The molecular structure of compound (I) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 5
The molecular structure of compound (VI) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 3
The molecular structure of compound (IV) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. ring are 0.330 (5), 0.332 (6) and 0.351 (4) Å in compounds (IV)-(VI), respectively, and, in each case, the aryl substituent at atom C5 occupies the axial site. In compound (VI), the methoxy C atom is displaced from the plane of the adjacent aryl ring by only 0.215 (6) Å : associated with this near planarity, the two exocyclic O-C-C angles at atom C34 differ by almost 10 , as is frequently observed in near-planar alkoxyarene systems (Seip & Seip, 1973;Ferguson et al., 1996).

Supramolecular features
Despite the presence of a carbonyl group in compounds (I) and (II), their structures do not contain any C-HÁ Á ÁO hydrogen bonds (Table 1): there are no intermolecular CÁ Á ÁH contact distances less than 2.8 Å , well beyond the sum of the van der Waals radii, 2.68 Å (Rowland & Taylor, 1996). The structures do, however, contain two C-HÁ Á Á(arene) hydrogen bonds, both involving the same ring (C31-C36) as the acceptor, with one C-H donor on each face of the ring and with H13 i Á Á ÁCg1Á Á ÁH35 ii angles of 158 in (I) and 157 in (II), where Cg1 represents the centroid of the (C31-C36) ring [symmetry codes: (i) 1 À x, 1 À y, 1 À z; (ii) x, 1 2 À y, 1 2 + z]. The combination of these two C-HÁ Á Á hydrogen bonds links the molecules into a sheet lying parallel to (100) and occupying the whole domain 0 < x < 1.0 (Fig. 7).
shown from database analyses (Brammer et al., 2001;Thallypally & Nangia, 2001) that halogen atoms bonded to C atoms are extremely poor acceptors of hydrogen bonds, so that this contact should not be regarded as structurally significant. The molecules of compound (VI) are linked by a combination of N-HÁ Á ÁS, N-HÁ Á ÁN and C-HÁ Á Á(arene) hydrogen bonds to form a complex sheet lying parallel to (001) in the domain 0 < z < 1 2 ( Fig. 9): a second sheet, related to the first by inversion lies in the domain ( 1 2 < z < 1.0). The only direction-specific intermolecular contact between adjacent sheets is of the C-HÁ Á ÁO type; however, this involves a C-H bond in a methyl group, which is probably undergoing fast rotation about the adjacent C-O bond (Riddell & Rogerson, 1996 and, in addition, it has a very small D-HÁ Á ÁA angle, indicating a very small interaction energy (Wood et al., 2009). On both these grounds, this contact can be regarded as having negligible structural significance, so that the supramolecular assembly in (VI) is two-dimensional.

Database survey
It is of interest to briefly compare the structures of the reduced pyrazole derivatives (IV)-(VI) reported here with those of some related compounds. Although there are no records of any 4,5-dihydropyrazole-1-carbothioamides recorded in the Cambridge Structural Database (CSD version 5.40, update of December 2019; Groom et al., 2016), there are several examples of 4,5-dihydropyrazole-1-carboxamides which contain a CONH 2 substituent, as opposed to the CSNH 2 substituent in compounds (IV)-(VI). Both 3-ethyl-5-hydroxy-5-(trifluoro- Part of the crystal structure of compound (VI), showing the formation of a hydrogen-bonded sheet running parallel to (001). Hydrogen bonds are shown as dashed lines and, for the sake of clarity, the H atoms not involved in the motifs shown have been omitted.

Figure 7
Part of the crystal structure of compound (I), showing the formation of a hydrogen-bonded sheet running parallel to (100). Hydrogen bonds are shown as dashed lines and, for the sake of clarity, the H atoms not involved in the motifs shown have been omitted.

Synthesis and crystallization
Samples of the chalcones (I)-(III) were prepared using the published methods (Hans et al., 2010;Yuan et al., 2009;Yu et al., 2016;Yadav et al., 2017): crystals of compounds (I) and (II), which were suitable for single-crystal X-ray diffraction, were grown by slow evaporation, at ambient temperature and in the presence of air from a solution in methanol. Despite repeated attempts, no suitable crystals of (III) could be obtained.
Crystals of compounds (IV)-(VI), which were suitable for single-crystal X-ray diffraction analysis, were selected directly from the analytical samples. For all structures, data collection: APEX2 (Bruker, 2012); cell refinement: APEX2/SAINT (Bruker, 2012); data reduction: SAINT/XPREP (Bruker, 2012); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b) and PLATON (Spek, 2020).  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.

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Acta Cryst. (2020). E76, 360-365 where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.50 e Å −3 Δρ min = −0.46 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.

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Acta Cryst. (2020). E76, 360-365 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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )