Crystal structure and Hirshfeld surface analysis of 5-[(5-nitro-1H-indazol-1-yl)methyl]-3-phenyl-4,5-dihydroisoxazole

In the title compound the indazole portion is planar and the nitro group and the pendant phenyl ring are coplanar within 7°. Oblique stacks along the a-axis direction are formed by π–π-stacking interactions between the indazole unit and the pendant phenyl rings of adjacent molecules. The stacks are linked into pairs through C—H⋯O hydrogen bonds.

In the title compound, C 17 H 14 N 4 O 3 , the indazole unit is planar to within 0.0171 (10) Å and makes dihedral angles of 6.50 (6) and 6.79 (4) , respectively, with the nitro and pendant phenyl groups. The conformation of the oxazole ring is best described as an envelope. In the crystal, oblique stacks along the a-axis direction are formed bystacking interactions between the indazole unit and the pendant phenyl rings of adjacent molecules. The stacks are linked into pairs through C-HÁ Á ÁO hydrogen bonds. Hirshfeld surface analysis and twodimensional fingerprint plots indicate that the most important contributions to the crystal packing are from HÁ Á ÁH (36.3%), OÁ Á ÁH/HÁ Á ÁO (23.4%), CÁ Á ÁH/ HÁ Á ÁC (13.4%) and NÁ Á ÁH/HÁ Á ÁN (11.4%) interactions.

Chemical context
Indazole derivatives are of pharmaceutical interest in a variety of therapeutic areas. They exhibit a variety of biological activities such as HIV protease inhibition (Patel et al., 1999), antiarrhythmic and analgesic activities (Mosti et al., 2000), and antitumor activity and antihypertensive properties (Bouissane et al., 2006;Abbassi et al., 2012). The present work is a continuation of an investigation of indazole derivatives published by our team (Boulhaoua et al., 2015). In this context, we synthesized the title compound by reaction of benzaldoxime with 1-allyl-5-nitro-1H-indazole in a biphasic medium (water-chloroform). We report herein its crystal and molecular structures along with the Hirshfeld surface analysis. ISSN 2056-9890

Structural commentary
In the title compound ( Fig. 1), the indazole portion is planar to within 0.0171 (10) Å (r.m.s. deviation = 0.0095) with atom C6 the furthest from the mean plane. The nitro group is twisted out of this plane by 6.50 (6) while the pendant phenyl group makes a dihedral angle of 6.79 (4) with the plane of the indazole unit. A puckering analysis of the oxazole ring gave parameters Q(2) = 0.1499 (12) Å and '(2) = 325.7 (5) with the conformation best described as an envelope on C9.

Figure 3
Packing viewed along the a-axis direction. A portion of the intermolecular interactions, depicted as in Fig. 2, is shown.

Figure 1
The title molecule with the labelling scheme and 50% probability ellipsoids.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of the title compound, a Hirshfeld surface analysis was carried out by using CrystalExplorer17.5 (Turner et al., 2017). The d norm representation of the Hirshfeld surface reveals the close contacts of the hydrogen-bond donors and acceptors and other close contacts are also evident. The molecular Hirshfeld surfaces were performed using a standard (high) surface resolution with the three-dimensional d norm surfaces mapped over a fixed colour scale of À0.191 (red) to 1.051 (blue) Å . The red spots on the surface indicate the intermolecular contacts involved in the hydrogen bonds. In Fig. 4, the identified red spot is attributed to the HÁ Á ÁO close contacts which are due to the C-HÁ Á ÁO hydrogen bonds (Table 1). Fig. 5 shows the two-dimensional fingerprint plot for the sum of the contacts contributing to the Hirshfeld surface represented in normal mode. The OÁ Á ÁH/HÁ Á ÁO contacts (23.4%) between the oxygen atoms inside the surface and the hydrogen atoms outside the surface, d e + d i $2.3 Å are shown two symmetrical points at the top, bottom left and right, which are characteristic of C-HÁ Á ÁO hydrogen bond. The (d i , d e ) points associated with he HÁ Á ÁH contacts in this study (36.3%) are characterized by an end point that points to the origin and corresponds to d i = d e = 1.08 Å . CÁ Á ÁH/HÁ Á ÁC and NÁ Á ÁH/ HÁ Á ÁN interactions (13.4% and 11.4%, respectively) are represented by two symmetrical wings on the left and right sides. In addition, the CÁ Á ÁC (7.5%), CÁ Á ÁN/NÁ Á ÁC (4.7%), OÁ Á ÁC/CÁ Á ÁO (2.2%) and OÁ Á ÁN/NÁ Á ÁO (0.9%) contacts contribute to the Hirshfeld surface.
A view of the three-dimensional Hirshfeld surface of the title compound plotted over molecular electrostatic potential in the range À0.0698 to 0.0535 a.u. using the STO-3G basis set at the Hartree-Fock level of theory is shown in Fig. 6. The C-HÁ Á ÁO hydrogen-bond donors and acceptors are shown as blue and red areas around the atoms related with positive (hydrogen-bond donors) and negative (hydrogen-bond acceptors) electrostatic potentials, respectively.

Synthesis and crystallization
To a solution of 1-allyl-5-nitro-1H-indazole (0.5 g, 2.46 mmol) and benzaldoxime (4.9 mmol, 0.6 g) in chloroform (20 mL), a solution of sodium hypochlorite 24% (10 mL) was added dropwise to the mixture and stirred at 273 K for 4h. The resulting mixture was washed with water, dried over MgSO 4 and the solvent was evaporated under reduced pressure. The Hirshfeld surface mapped over d norm to visualize the intermolecular interactions.

Figure 5
The fingerprint plot for the title compound.

Figure 6
A view of the three-dimensional Hirshfeld surface plotted over molecular electrostatic potential in the range À0.0698 to 0.0535 a.u. using the STO-3 G basis set at the Hartree-Fock level of theory. residue was then purified by column chromatography on silica gel using a mixture of hexane/ethyl acetate (v/v = 80/20) as eluent. Colourless crystals were isolated when the solvent was allowed to evaporate (yield: 65%).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were located in a difference-Fourier map and freely refined.   (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Special details
Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, colllected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = -30.00 and 210.00°. The scan time was 20 sec/frame. 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. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.