Different conformations and packing motifs in the crystal structures of four thiophene–carbohydrazide–pyridine derivatives

The title compounds show different packing motifs including chains mediated by N—H⋯N and N—H⋯O hydrogen bonds.


Chemical context
Various thiophene-carbohydrazide derivatives containing a T-C( O)-NH-N CH-R (T = thiophene ring) building unit have been previously investigated by some of us for their anti-cancer (Cardoso et al., 2017) and anti-tuberculosis (Cardoso et al., 2014(Cardoso et al., , 2016a properties. Other workers have reported their analgesic activities (Lima et al., 2000) and their potential uses as tunable photo switches (van Dijken et al., 2015). The use of these compounds as multi-dentate chelating ligands has been described by Gholivand et al. (2016) and Abbas et al. (2021).

Structural commentary
The molecular structures of (I)-(IV) are shown in Figs. 1-4, respectively and they all confirm the structures (atomic connectivities) postulated in the previous studies noted in the synthesis section: each compound crystallizes with one molecule in the asymmetric unit and there is no suggestion that any of these compounds exist in the 'enol' -C(OH) Ntautomer in the solid state.
In (I) (Fig. 1), the conformation about the N2 C6 bond [1.280 (5) Å ] is E and the C5-N1-N2-C6 torsion angle is 175.1 (4) . The oxygen atom of the carbonyl group and the sulfur atom of the thiophene ring lie on the same side of the molecule [S1-C4-C5-O1 = À4.9 (6) ] whereas atom N3 of the pyridine ring lies on the opposite side. The dihedral angle between the thiophene and pyridine rings is 21.4 (2) and the largest twist in the molecule occurs about the C6-C7 bond [N2-C6-C7-C8 = À11.8 (7) ]. The N1-N2 bond length of 1.384 (5) Å in (I) is significantly shorter than a typical N-N single bond ($1.44 Å ), which suggests substantial delocalization of electrons with the adjacent C5 O1 carbonyl group and the N2 C6 double bond, as observed previously for related compounds (Cardoso et al., 2016c). Otherwise, the bond lengths and angles in (I) may be regarded as unexceptional.

Figure 3
The molecular structure of (III) showing 50% displacement ellipsoids. The short C-HÁ Á ÁS contact is indicated by a double-dashed line.
Given these distances, any aromatic ring-stacking effects that contribute to the cohesion and stability of the crystal must be weak to non-existent.
In order to gain more insight into these different packing motifs, the Hirshfeld surfaces and fingerprint plots for (I)-(IV) were calculated using CrystalExplorer (Turner et al., 2017) following the approach recently described by Tan et al. (2019). The Hirshfeld surfaces (see supporting information) show the expected red spots (close contacts) in the vicinities of the various donor and acceptor atoms.
The fingerprint plots for (I)-(IV) decomposed into the different percentage contact types (Table 5) show that the different contributions are broadly similar, with HÁ Á ÁH (van der Waals) contacts the most significant for each structure, followed by CÁ Á ÁH/HÁ Á ÁC. The OÁ Á ÁH/HÁ Á ÁO and NÁ Á ÁH/ HÁ Á ÁN contributions are almost the same for the four structures, despite the lack of classical hydrogen bonds in (III). The SÁ Á ÁH/HÁ Á ÁS percentage contributions for (I) and (IV) are notably greater than those for (II) and (III), possibly because the S atom is 'facing outwards' in the former structures but is associated with an intramolecular C-HÁ Á ÁS close contact arising from the pyridine ring in the latter structures. It is notable that the percentage of OÁ Á ÁO contacts is zero in all structures, presumably reflecting the fact that 'bare' O atoms avoid each other in the solid state for electrostatic reasons.

Synthesis and crystallization
Compounds (I) and (II) were prepared by a literature procedure (Lima et al., 2000) and single crystals suitable for data collection were recrystallized from ethanol solution at room temperature. For the syntheses and spectroscopic characterizations of (III) and (IV), see Cardoso et al. (2016a) and 622 Garbutt et al. C 11 H 9 N 3 OS, C 11 H 9 N 3 OS, C 12 H 11 N 3 OS and C 12 H 11 N 3 OS Acta Cryst. (2022). E78, 619-624 research communications Table 5 Hirshfeld fingerprint contact percentages for (I)-(IV).

N′-[(E)-Pyridin-3-ylmethylidene]thiophene-2-carbohydrazide (I)
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.

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.

N-Methyl-N′-[(E)-pyridin-2-ylmethylidene]thiophene-2-carbohydrazide (III)
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.