Comparison of crystal structures of 4-(benzo[b]thiophen-2-yl)-5-(3,4,5-trimethoxyphenyl)-2H-1,2,3-triazole and 4-(benzo[b]thiophen-2-yl)-2-methyl-5-(3,4,5-trimethoxyphenyl)-2H-1,2,3-triazole

In the crystal structure of (I), the molecules are linked into chains by N—H⋯O hydrogen bonds with (5) ring motifs. After the N-methylation of structure (I), no hydrogen-bonding interactions were observed for structure (II).

The title compound, C 19 H 17 N 3 O 3 S (I), was prepared by a [3 + 2]cycloaddition azide condensation reaction using sodium azide and l-proline as a Lewis base catalyst. N-Methylation of compound (I) using CH 3 I gave compound (II), C 20 H 19 N 3 O 3 S. The benzothiophene ring systems in (I) and (II) are almost planar, with r.m.s deviations from the mean plane = 0.0205 (14) in (I) and 0.016 (2) Å in (II). In (I) and (II), the triazole rings make dihedral angles of 32.68 (5) and 10.43 (8) , respectively, with the mean planes of the benzothiophene ring systems. The trimethoxy phenyl rings make dihedral angles with the benzothiophene rings of 38.48 (4) in (I) and 60.43 (5) in (II). In the crystal of (I), the molecules are linked into chains by N-HÁ Á ÁO hydrogen bonds with R 2 1 (5) ring motifs. After the N-methylation of structure (I), no hydrogen-bonding interactions were observed for structure (II). The crystal structure of (II) has a minor component of disorder that corresponds to a 180 flip of the benzothiophene ring system [occupancy ratio 0.9363 (14):0.0637 (14)].

Chemical context
In continuation of our work on the development of benzothiophene cyano combretastatin A-4 analogs as anti-cancer agents (Penthala et al., 2013), we have synthesized a series of novel CA-4 analogs by constructing a triazole ring structure (I) by chemical modification of the cyano group on the stilbene unit of cyano-CA-4 analogs utilizing a [3 + 2]cycloaddition azide condensation reaction with sodium azide in the presence of l-proline Lewis base as catalyst. This chemical modification is essential to restrict the tendency toward cis-trans isomerization of the cyano-stilbene moiety in cyano-CA-4 analogs (Penthala et al., 2013). To further check the position of the hydrogen atom in the triazole ring system in (I), an Nmethylation reaction was carried out on (I) using CH 3 I, resulting in compound (II). ISSN 1600-5368

Structural commentary
In order to obtain detailed information on the structural conformations of (I) and (II) for analysis of structure-activity relationships (SAR), including the position of the hydrogen atom in the triazole ring system of (I) and the position of methylation on the triazole ring system in (II), we determined the X-ray crystal structures of (I) and (II); see Figs. 1 and 2, respectively.

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.

Figure 3
Hydrogen bonding in the crystal structure of (I), viewed along the b axis. Dashed lines represent hydrogen bonds, which join molecules into chains along the [101] direction.

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 by intermolecular hydrogen bonds (N2-H2NÁ Á ÁO2 and N2-H2NÁ Á ÁO3), forming R 2 1 (5) ring motifs (Table 3), which propagate as chains along the [101] direction. Contacts between adjacent chains form two-dimensional pleated-sheet networks in the ac plane. No significant hydrogen-bonding interactions were found in the structure of (II). Crystal packing of (II), as viewed along the b axis. Table 3 Hydrogen-bond geometry (Å , ) for (I).

Synthesis and crystallization
The title compounds were prepared according to a previously reported procedure . Recrystallization from methanol afforded (I) and (II) as yellow and pale-yellow crystalline products, respectively, which were suitable for X-ray analysis.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 4. H atoms were found in difference Fourier maps. Carbon-bound hydrogens were subsequently placed at idealized positions with constrained distances of 0.98 (RCH 3 ) and 0.95 Å (Csp 2 H). Coordinates of the N-bound hydrogen were refined freely. U iso (H) values were set to either 1.2U eq or 1.5U eq (RCH 3 ) of the attached atom. Refinement progress was checked using PLATON (Spek, 2009) and by an R-tensor (Parkin, 2000). To ensure satisfactory refinement of disordered groups in the structure, a combination of constraints and restraints was employed. The constraints (SHELXL command EADP) were used to fix overlapping fragments. Restraints were used to maintain the integrity of ill-defined or disordered groups (SHELXL commands SAME and RIGU).

(I) 4-(Benzo[b]thiophen-2-yl)-5-(3,4,5-trimethoxyphenyl)-2H-1,2,3-triazole
Special details Experimental. The crystal was mounted with polyisobutene oil on the tip of a fine glass fibre, fastened in a copper mounting pin with electrical solder. It was placed directly into the cold stream of a liquid nitrogen based cryostat, according to published methods (Hope, H. (1994). Prog. Inorg. Chem. 41, 1-19; Parkin, S. & Hope, H. (1998). J. Appl. Cryst. 31,[945][946][947][948][949][950][951][952][953]. Diffraction data were collected with the crystal at 90 K, which is standard practice in this laboratory for the majority of flash-cooled crystals. Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement progress was checked using PLATON (Spek, 2009) and by an R-tensor (Parkin, 2000). The final model was further checked with the IUCr utility checkCIF.