Crystal structure and Hirshfeld surface analysis of 4-allyl-2-methoxy-6-nitrophenol

The crystal structure of 4-allyl-2-methoxy-6-nitrophenol, which crystallizes in the centrosymmetric space group P with three independent molecules in the asymmetric unit, is reported along with the Hirshfeld surface analysis.


Chemical context
Eugenol, the main constituent of clove essential oil, has many interesting biological properties and participates in the synthesis of bioactive compounds (Kaufman, 2015). The nitroeugenol isomers were tested for their antifungal activity, growth inhibitory activity on human tumor cell lines (Carrasco et al., 2012(Carrasco et al., , 2008, and antioxidant activity (Hidalgo et al., 2009). We report here the synthesis, structure, spectrometric and spectroscopic characterization of the title compound along with an analysis of the calculated Hirshfeld surface and the two-dimensional fingerprint plots.

Hirshfeld surface analysis
In order to explore the nature of the intermolecular contacts and their role in the crystal packing, Hirshfeld surfaces (Spackman & Jayatilaka, 2009) and the associated twodimensional fingerprint plots (McKinnon et al., 2007) were calculated using Crystal Explorer 17.5 (Turner et al., 2017). The three-dimensional molecular Hirshfeld surfaces of the three molecules Mol-N1, Mol-N2 and Mol-N3 and the overall surface were generated using a high standard surface resolution colour-mapped over the normalized contact distance. The red, white and blue regions visible on the d norm surfaces indicate contacts with distances shorter, longer and equal to the van der Waals radii ( Fig. 4a and 5a). The shape-index of the Hirshfeld surface is a tool to visualize thestacking interactions ( Fig. 4b and 5b). The red spots in Fig. 4a correspond to the strong C-HÁ Á ÁO hydrogen-bond interactions in the crystal structure; in Mol-N1 two of them involve the O atoms of the methoxy (O1) and nitro (O3) groups as acceptors with allyl H atoms (C22B-H22BÁ Á ÁO1 and C12B-H12BÁ Á ÁO3), while the other is due to the interatomic interaction between the aromatic H9 donor atom and the nitro O7 oxygen atom (C9-H9Á Á ÁO7 Symmetry codes: (i) Àx þ 1; Ày þ 1; Àz þ 1; (ii) Àx þ 2; Ày þ 1; Àz þ 2.

Figure 2
Partial crystal packing of the title compound showing molecules connected by hydrogen bonds (dashed cyan lines) andinteractions (dashed green lines).

Figure 3
Crystal packing of the title compound viewed along the a axis showing molecules linked by hydrogen bonds (dashed cyan lines).

Figure 1
The asymmetric unit of the title compound with the displacement ellipsoids drawn at the 50% probability level. H atoms are represented as small circles. Intra-and intermolecular hydrogen bonds are shown as dashed lines.
hydrogen bonds and OÁ Á ÁO interactions are characterized by smaller red spots close to each other on the surface, where the faint red spot indicating the O-HÁ Á ÁO interactions is associated with the longest OÁ Á ÁO contact of 2.96 (3) Å in Mol-N1 and Mol-N3. In Mol-N2, the red spots correspond to C-HÁ Á ÁO (C9-H9Á Á ÁO7 and C12A-H12AÁ Á ÁO12) and C-HÁ Á ÁC (C20-H20BÁ Á ÁC11A) hydrogen-bond interactions. The corresponding fingerprint plots for each of the independent molecules and for the entire asymmetric unit, showing characteristic pseudo-symmetric wings in the d e and d i diagonal axes, and those delineated into HÁ Á ÁH, OÁ Á ÁH/HÁ Á ÁO, CÁ Á ÁH/HÁ Á ÁC and CÁ Á ÁC contacts are illustrated in Fig. 6. The result of the quantitative analysis of all types of intermolecular contacts present in the title compound is summarized in Fig. 7. The most important interaction is HÁ Á ÁH, contributing 45.4% to the overall crystal packing (Fig. 6b), which is reflected in the widely scattered points of high density due to the large hydrogen-atom content of the molecule. The contribution from the OÁ Á ÁH/HÁ Á ÁO contacts (31.7%), corresponding to C-HÁ Á ÁO and O-HÁ Á ÁO interactions, is represented by a pair of sharp spikes characteristic of a strong hydrogen-bond interaction with d e + d i ' 2.5Å (Fig. 6c). In the absence of weak C-HÁ Á Á interactions in the crystal, the pair of characteristic wings in the fingerprint plot delineated into HÁ Á ÁC/ CÁ Á ÁH contacts (7.7% contribution) have a symmetrical distribution of points ( Hirshfeld surface of the title compound (symmetry-independent molecules Mol-N1, Mol-N2 and Mol-N3), with (a) d norm with the interaction of neighbouring molecules and (b) shape-index.

Figure 5
Views of the Hirshfeld surface for a reference molecule of the title compound mapped over (a) d norm , (b) shape-index and (c) the shapeindex property highlighting theinteractions as black dashed lines.

Figure 7
Percentage contribution of various intermolecular interactions in the title compound obtained from decomposed fingerprint plots.

Database survey
A search of the Cambridge Structural Database (CSD, Version 5.40, May 2019; Groom et al., 2016) of eugenol derivatives revealed two compounds with very similar structures but with a different position of the nitro group or with the hydroxide group substituted by an acetate group, viz. 4-allyl-2methoxy-5-nitrophenyl acetate (refcode: TEJREG; Carrasco-Altamirano et al., 2006) and 4-hydroxy-3-methoxy-5-nitroacetophenone (5-nitroapocynin) (MUCDOE; Babu et al., 2009). A third related compound, 4-hydroxy-3-methoxy-5nitrobenzaldehyde, has recently been reported (Vusak et al., 2020). All of these compounds exhibit intramolecular hydrogen bonds involving the nitro O atoms with the H atoms of the hydroxide group, and other intermolecular hydrogen bonds, in addition tointeractions, which assure the crystal cohesion.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The C-bound H atoms were located in a difference-Fourier map and refined as riding with C-H = 0.93-0.97 Å , and U iso (H) = 1.2 U eq (C) or 1.5U eq (C) for methyl H atoms. A rotating model was used for the methyl groups. The hydroxyl H atoms were located in a difference-Fourier map and refined freely. The two allyl groups of Mol- The FT-IR spectrum of the title compound.  (9):0.332 (9) respectively. One outlier (100) was omitted in the cycles of refinement.
SHELXL2016/6 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).  (2) 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.