Crystal structures of (Z)-5-[2-(benzo[b]thiophen-2-yl)-1-(3,5-dimethoxyphenyl)ethenyl]-1H-tetrazole and (Z)-5-[2-(benzo[b]thiophen-3-yl)-1-(3,4,5-trimethoxyphenyl)ethenyl]-1H-tetrazole

In both structures, molecules are linked into hydrogen-bonded chains. In (Z)-5-[2-(benzo[b]thiophen-2-yl)-1-(3,5-dimethoxyphenyl)ethenyl]-1H-tetrazole methanol monosolvate, these chains involve both tetrazole and methanol, and are parallel to the b axis. In (Z)-5-[2-(benzo[b]thiophen-3-yl)-1-(3,4,5-trimethoxyphenyl)ethenyl]-1H-tetrazole, molecules are linked into chains parallel to the a axis by N—H⋯N hydrogen bonds between adjacent tetrazole rings.


Chemical context
We have reported on benzothiophene cyanocombretastatin A-4 analogs (Penthala et al., 2013), and benzothiophene triazolylcombretastatin A-4 analogs as promising anti-cancer agents (Penthala et al., 2015). Previously, we published the synthesis of triazolylcombretastatin A-4 analogs utilizing a [3 + 2]cycloaddition azide condensation reaction with sodium azide in the presence of l-proline as catalyst (Penthala et al., 2014a). In a continuation of our work on the chemical modification of the cyano group on the stilbene moiety of cyanocombretastatin A-4 analogs (Penthala et al., 2014a), we have recently synthesized tetrazolylcombretastatin A-4 analogs as potential anti-cancer agents (Penthala et al., 2016).

Structural commentary
Single crystal X-ray analysis was carried out to obtain the structural conformations of the tetrazolylcombretastatin A-4 analogs (I) and (II) for the analysis of structure-activity relationships (SAR), the relevance of the geometry of the ISSN 2056-9890 tetrazole ring on the stilbene scaffold and to confirm the position of the hydrogen atom in the tetrazole ring system. The single crystal X-ray structures of (I) and (II) are shown in Figs. 1 and 2, respectively.
The benzothiophene rings are almost planar with r.m.s. deviations from the mean plane of 0.0084 and 0.0037 Å in (I) and 0.0084 Å in (II), with bond distances and angles comparable with those reported for other benzothiophene derivatives (Sonar et al., 2007;Penthala et al., 2014b). The tetrazole rings make dihedral angles with the mean plane of the benzothiophene rings of 88.81 (13) and 88.92 (13) in (I), and 60.94 (6) in (II). The dimethoxyphenyl ring in (I) and trimethoxyphenyl ring in (II) make dihedral angles with the benzothiophene rings of 23.91 (8) and 24.99 (8) in (I) and 84.47 (3) in (II). Bond lengths and angles in both (I) and (II) are, by and large, unremarkable.

Supramolecular features
Hydrogen bonding and the mode of packing of (I) is illustrated in Fig. 3, and the mode of packing of (II) is illustrated in Fig. 4. In the structure of (I), the molecules are linked into hydrogen-bonded (Table 1) chains parallel to the crystallographic b axis involving interaction between tetrazoletetrazole (N-HÁ Á ÁN), tetrazole-methanol (O-HÁ Á ÁN and N-HÁ Á ÁO), and methanol-methanol (O-HÁ Á ÁO). These chains are bidirectional, as the hydrogen atoms on the tetrazole rings and the methanol oxygen atom appear to be disordered over two positions. In the structure of (II), the molecules are linked into chains parallel to the a axis by intermolecular N-HÁ Á ÁN hydrogen bonds (Table 2) between adjacent tetrazole rings.

Database survey
A search of the 2015 Cambridge Structural Database (Groom & Allen, 2014) for tetrazole bonded via its carbon atom to another carbon atom yielded 255 hits. Of these, only two were bonded to an sp 2 carbon atom, namely 5-(2H-chromen-3-yl)-

Figure 1
The molecular structure of (I), with displacement ellipsoids drawn at the 50% probability level.

Figure 2
The molecular structure of (II), with displacement ellipsoids drawn at the 50% probability level.

Synthesis and crystallization
The title compounds (I) and (II) were prepared by utilizing our recently reported literature procedure (Penthala et al., 2016). Recrystallization of the compounds from methanol afforded (I) and (II) as pale-yellow crystalline products which were suitable for X-ray analysis.

Refinement details
Crystal data, data collection and refinement details for both (I) and (II) are summarized in Table 3. H atoms were found in difference Fourier maps and subsequently placed at idealized positions with constrained distances of 0.95 Å (R 2 Csp 2 H), 0.98 Å (RCH 3 ), 0.84 Å (OH), 0.88 Å (Nsp 2 H). U iso (H) values were set to either 1.2U eq or 1.5U eq (RCH 3 , OH) of the attached atom. Final models were checked using PLATON (Spek, 2009), RT (Parkin, 2000, and by checkCIF. Refinement of (I) was hampered by the presence of pseudosymmetry. An alternative model using space group Pccn was also refined, but the overall quality of the refinement was not as good as the P2 1 2 1 2 model given here. Indeed, the ADDSYM routine in PLATON (Spek, 2009) suggests a missing inversion centre and transformation to Pccn, but that model did not refine well (R 1 > 9%). Other alternatives using space groups Pcc2, Pban, and Pna2 1 were much less satisfactory. Not surprisingly, the P2 1 2 1 2 model was twinned by inversion, which was dealt with using standard SHELXL methods (TWIN and BASF commands).
The hydrogen on the tetrazole ring was initially placed solely on the atoms labelled N1A and N1B. This assignment results in impossible clashes with symmetry equivalents about the twofold axis. Since there were suitable small difference map peaks for hydrogen atoms attached to atoms N4A and N4B as well as N1A and N1B, these hydrogen atoms were included as split over the two sites at half occupancy. Disorder of the tetrazole ring hydrogen atoms in this way also requires that the hydroxyl hydrogen atoms of the methanol molecules are disordered. Again, suitable (albeit small) difference map  Table 2 Hydrogen-bond geometry (Å , ) for (II).  Symmetry codes: (i) Àx; Ày; z; (ii) Àx þ 1; Ày þ 1; z; (iii) Àx þ 1; Ày; z.

Figure 3
Crystal packing of (I), viewed down the c axis.

Figure 4
Crystal packing of (II), viewed down the c axis.
peaks were apparent. Further evidence for the disorder is that the distances C11A-N1A, C11A-N4A and C11B-N1B, C11B-N4B are all very similar, indicating that the C N double bond and C-N single bond in these rings are scrambled. Not surprisingly, convergence of the OH hydrogen-atom positions was rather problematic.    Absolute structure: Refined as an inversion twin Absolute structure parameter: 0.50 (3) Special details Experimental. The crystal was mounted using polyisobutene oil on the tip of a fine glass fibre, which was fastened in a copper mounting pin with electrical solder. It was placed directly into the cold gas stream of a liquid-nitrogen based cryostat. Diffraction data were collected with the crystal at 90K, which is standard practice in this laboratory for the majority of flash-cooled crystals. 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. Refinement. Refined as a 2-component inversion twin.