Crystal structures and Hirshfeld surfaces of differently substituted (E)-N′-benzylidene-N-methyl-2-(thiophen-2-yl)acetohydrazides

The title compounds feature various types of weak intermolecular interactions but their decomposed Hirshfeld fingerprint plots show significant differences.

The syntheses and crystal structures of (E)-N 0 -(3-cyanobenzylidene)-N-methyl-2-(thiophen-2-yl)acetohydrazide, C 15 H 13 N 3 OS, (I), and (E)-N 0 -(4-methoxybenzylidene)-N-methyl-2-(thiophen-2-yl)acetohydrazide, C 15 H 16 N 2 O 2 S, (II), with different substituents in the meta and para position of the benzene ring are described. Compounds (I) and (II) both crystallize with two molecules in the asymmetric unit, with generally similar conformations [r.m.s. overlay fits for (I) and (II) of 0.334 and 0.280 Å , respectively] that approximate to L-shapes. The thiophene rings in (I) are well ordered, whereas those in (II) exhibit 'flip' rotational disorder [occupancies 0.662 (2) and 0.338 (2) for molecule 1, and 0.549 (3) and 0.451 (3) for molecule 2]. The packing for (I) features short C-HÁ Á ÁO interactions arising from the C-H grouping adjacent to the cyanide group and C-HÁ Á ÁN c (c = cyanide) links arising from the methine groups to generate [110] double chains. Weak C-HÁ Á Á interactions interlink the chains into a three-dimensional network. The packing for (II) features numerous C-HÁ Á ÁO and C-HÁ Á Á interactions arising from different donor groups to generate a three-dimensional network. Hirshfeld fingerprint plots indicate significant differences in the percentage contact surfaces for (I) and (II).

Figure 3
The molecular structure of (II) showing 50% displacement ellipsoids. Only the major orientation of the thiophene ring is shown.

Figure 1
The molecular structure of (I) showing 50% displacement ellipsoids.

Figure 5
Fragment of a [110] hydrogen-bonded chain in the crystal of (I). Symmetry codes as in Table 1; additionally (iv) x + 1, y, z À 1. All hydrogen atoms not involved in hydrogen bonds omitted for clarity.

Figure 4
Overlay plot of molecules A (red) and B (black) for (II). Only the major orientation of the thiophene ring is shown.
symmetry. We may speculate that these C-H groupings have been 'activated' (made more acidic) by being adjacent to the electron-withdrawing cyanide group (Pedireddi & Desiraju, 1992 (18) loops are apparent. The chains are cross-linked by C-HÁ Á Á interactions, with all the rings (i.e. both thiophene and both benzene rings) acting as acceptors. The shortest centroid-centroid separation between aromatic rings is 3.9895 (10) Å , indicating that anystacking effects in (I) are very weak at best.
The packing for (II) is less 'tidy' in the sense that C-H entities belonging to several different groups (benzene ring, methylene group adjacent to the thiophene ring, thiophene ring, methoxy group) act as donors and none of the C-HÁ Á ÁO links are particularly short. There are molecule A ! molecule A, A ! B, B ! A and B ! B links. Perhaps the most notable are a pair of bonds arising from the methylene groups that generate A + B dimers incorporating R 2 2 (8) loops, as shown in Fig. 3 above. A number of C-HÁ Á Á interactions are observed, with all the rings acting as acceptors, but there are no aromaticstacking interactions in (II) (shortest centroid-centroid separation > 4.9Å ). When the different intermolecular interactions are taken together, a threedimensional network arises in the crystal of (II).

Hirshfeld analysis
Hirshfeld surface fingerprint plots for (I) (Fig. 6) and (II) (Fig. 7) were calculated with CrystalExplorer17 (Turner et al., 2017). The plot for (I) has 'wingtip' features that correspond to the short C-HÁ Á ÁO hydrogen bonds described above, although the wingtips are not as pronounced as those seen for classical hydrogen bonds (compare: McKinnon et al., 2007). In (II), the wingtips are less apparent, presumably reflecting the longer (and weaker) C-HÁ Á ÁO interactions in this structure, even though there are more of them in (II) than in (I).
When the fingerprint plots for (I) and (II) are decomposed into the separate types of contacts (McKinnon et al., 2007), some interesting differences arise (Table 3): HÁ Á ÁH contacts represent the highest percentage in both structures, but they are far more significant in (II), representing over half the contact area, some 20% more than in (I). This deficit is largely made up by NÁ Á ÁH/HÁ Á ÁN contacts (i.e. the C-HÁ Á ÁN hydrogen bonds) in (I), which are barely present in (II). The OÁ Á ÁH/HÁ Á ÁO contacts are slightly higher in (II) than (I), presumably reflecting that fact that there are many more C-HÁ Á ÁO bonds in (II) (compare Table 2), although the HÁ Á ÁO contacts are shorter in (I). The percentages of CÁ Á ÁH/HÁ Á ÁC contacts in the two compounds are very similar, whereas Table 3 Hirshfeld contact interactions (%).

Figure 6
Hirshfeld fingerprint plot for (I)

Figure 7
Hirshfeld fingerprint plot for (II) CÁ Á ÁC contacts are insignificant in both structures, which presumably correlates with the very weakstacking described above. Finally, SÁ Á ÁH/HÁ Á ÁS contacts are clearly more prominent in (I) although any C-HÁ Á ÁS bonds in (I) would be regarded as very weak at best (shortest HÁ Á ÁS separation = 2.95 Å ). When the two molecules in the asymmetric unit of (I) are compared with each other (Table 3), there is little difference between them and the same applies to (II).  (Ramírez et al., 2009b); OFEBIL (Cao et al., 2007), and EYUBAD, EYUBEH and EYUBIL: this latter trio of refcodes correspond to the three isomeric nitro compounds (Cardoso et al., 2016a) noted in the Chemical Context section above.

Synthesis and crystallization
The appropriate thienyl acetohydrazide derivative (Cardoso et al., 2014) (0.20 g, 1.0 equiv.) was suspended in acetone (5 ml) and potassium carbonate (4.0 equiv.) was added. The reaction mixture was stirred at room temperature for 30 minutes and methyl iodide (4.0 equiv.) was added. The reaction mixture was maintained at 313 K, until TLC indicated the reaction was complete. The mixture was then rotary evaporated to leave a residue, which was dissolved in water (20 ml) and extracted with ethyl acetate (3 Â 10 ml). The organic fractions were combined, dried with anhydrous MgSO 4 , filtered and the solvent evaporated at reduced pressure. The crystals used for the intensity data collections were recrystallized from methanol solution at room temperature to yield colourless plates of (I) and colourless slabs of (II).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. The hydrogen atoms were geometrically placed (C-H = 0.95-1.00 Å ) and refined as riding atoms. The constraint U iso (H) = 1.2U eq (carrier) or 1.5U eq (methyl carrier) was applied in all cases. The N-methyl group was allowed to rotate, but not to tip, to best fit the electron density (AFIX 137 instruction): in every case this group rotated from its initial orientation to minimize steric interaction with H7; the final orientation leads to a rather short C8-HÁ Á ÁO1 intramolecular contact but we do not regard this as a bond. The thiophene rings in both molecules of (II) show 'flip' rotational disorder. For both structures, data collection: CrystalClear (Rigaku, 2012); cell refinement: CrystalClear (Rigaku, 2012); data reduction: CrystalClear (Rigaku, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008). Program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015) for (I); SHELXL2014 (Sheldrick, 2015) for (II). For both structures, molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: publCIF (Westrip, 2010). 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.