Crystal, molecular structure and Hirshheld surface analysis of 5-hydroxy-3,6,7,8-tetramethoxyflavone

5-Hydroxy-3,6,7,8-tetramethoxyflavone was isolated from a butanol extract of the herb Scutellaria nepetoides M. Pop. and its structure has been established by X-ray crystallographic analysis.

The title compound [systematic name: 8-hydroxy-2,5,6,7-tetramethoxy-3phenylnaphthalen-1(4H)-one], C 19 H 18 O 7 , is a flavone that was isolated from a butanol extract of the herb Scutellaria nepetoides M. Pop. The flavone molecule is almost planar, with a dihedral angle between the planes of the benzopyran-4one group and the attached phenyl ring of 6.4 (4) . The 5-hydroxy group forms a strong intramolecular hydrogen bond with the carbonyl group, resulting in a sixmembered hydrogen-bonded ring. The crystal structure has triclinic (P1) symmetry. In the crystal, the molecules are linked by C-HÁ Á ÁO hydrogen bonds into a two dimensional network parallel to the ab plane. The Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from HÁ Á ÁH (53.9%) and HÁ Á ÁO/OÁ Á ÁH (20.9%) interactions.

Chemical context
Flavonoids are the most numerous class of natural phenolic compounds, which are characterized by structural diversity, high and versatile activity and low toxicity. Plants of the genus Scutellaria L. are widespread in Europe, North America, East Asia and are extensively used in traditional Chinese medicine (Shang et al., 2010). Flavonoids isolated from plants of the genus Scutellaria L. exhibit antitumor (Yu et al., 2007), hepatoprotective (Jang et al., 2003), antioxidant (Sauvage et al., 2010), anti-inflammatory (Dai et al., 2013), anticonvulsant (Park et al., 2007), antimicrobial (Arituluk et al., 2019) and antiviral activity (Leonova et al., 2020). The creation of drugs based on flavonoids is based on the establishment of the 'chemical structure-pharmacological properties' relationship, and the determination of the structure of a new flavonoid may become a key starting point.

Supramolecular features
In the crystal, the molecules are linked by C-HÁ Á ÁO hydrogen bonds into a two dimensional network parallel to the ab plane. A perspective view of the crystal packing in the unit cell is depicted in Fig. 2 and numerical details of the hydrogen bonds are presented in Table 1.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystals of the title compound, a Hirshfeld surface analysis was carried out using Crystal Explorer 17.5 (Turner et al., 2017). The Hirshfeld surface mapped over d norm (Fig. 3) shows the expected bright-red spots near atoms O3, O7, H16B, which are involved in the C-HÁ Á ÁO hydrogen-bonding interactions. Fingerprint plots (Fig. 4)  Crystal structure of the title compound in projection on the ac plane. Hydrogen bonds are shown as dashed lines. Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) x þ 1; y; z; (ii) x À 1; y; z.

Figure 1
The molecular structure of the title compound with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Synthesis and crystallization
Air-dried whole plants (1.1 kg) of Scutellaria nepetoides M.
Pop. were extracted three times (each 3 h) with butanol (5 l) at 353 K. The butanol filtrates were collected and concentrated under reduced pressure to provide 10.2 g of butanol extract. The butanol extract (1 g) was subjected to silica gel (60-100 mesh) column (gradient of butanol:water = 0:1, 2:8, 1:1, 8:2, 1:0) as eluent, and five fractions were collected according to TLC analysis. All fractions were concentrated under reduced pressure. A crystallization procedure with different solvents at high temperature was used to obtain the pure compounds. Fraction 5 (0.23 g) was eluted with butanol (100%) at 353 K and with ethanol (95%) at 343 K. The obtained polycrystals were removed from the butanol solution by filtration. Yellow prismatic single crystals were prepared by slow evaporation of butanol solution at room temperature.

Refinement
Crystal data, data collection and structure refinement details are summarized in     (Siemens, 1994).

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.