Crystal structure, Hirshfeld surface analysis and DFT calculations of (E)-3-[1-(2-hydroxyphenylanilino)ethylidene]-6-methylpyran-2,4-dione

The asymmetric unit contains three independent molecules differing slightly in conformation. Portions of the observed conformations are determined by intramolecular N—H⋯O hydrogen bonds. In the crystal, O—H⋯O hydrogen bonds form chains of molecules which are linked into corrugated sheets parallel to ( 03) by C—H⋯O hydrogen bonds together with π interactions between the carbonyl groups and 2-hydroxyphenyl rings. The layers are linked by further C—H⋯O hydrogen bonds.


Chemical context
Heterocyclic molecules play a very important role in life processes and are of major interest in the industrial development of dyes, pharmaceuticals, pesticides, and natural products (Saber et al., 2020;El Ghayati et al., 2021;Patra & Saxena, 2010). Therefore, scientists have devoted considerable effort to finding efficient synthetic methods for a wide variety of heterocyclic compounds (Yeh et al., 2014;Liaw et al., 2015). Among these molecules, pyrone derivatives constitute an important class in the heterocycle family since the pyrone structural unit is found in a wide variety of natural bioactive compounds (McGlacken & Fairlamb, 2005;Beckert et al., 1997) and also in a wide range of synthetic products with demonstrated efficacy in various fields such as the pharmaceutical and therapeutic field as cytotoxic (Calderó n-Montañ o et al., 2013), antitumor (Suzuki et al., 1997;Kondoh et al., 1998) and antimicrobial agents (Fairlamb et al., 2004). Another representative example of the pyrone class of compounds, kavalactones, possess many biological activities such as antituberculosis, local anesthetic, anticonvulsant, analgesic, anti-malarial, and sedative activities (Altomare et al., 1997;Scherer, 1998;Bilia et al., 2002;Ernst, 2007). In this work, we report the synthesis of (E)-3-[1-(2-hydroxyphenylanilino)ethylidene]-6-methylpyran-2,4-dione, (I) (Fig. 1) in good yield by the condensation of 2-aminophenol and dehydroacetic acid along with its crystal and molecular structures as well as the Hirshfeld surface analysis and the density functional theory (DFT) computational calculations carried out at the B3LYP/ 6-311G(d,p) levels.

Structural commentary
The asymmetric unit of the title compound comprises three independent molecules, two of which (those containing O5 and O9) differ modestly in the orientations of the methyl groups while the third differs more in conformation from the other two (Fig. 1). In each molecule, the conformation is partially determined by an intramolecular N-HÁ Á ÁO hydrogen bond ( Fig. 1 and Table 1), which can be described as a resonance-assisted hydrogen bond (RAHB). With reference to the scheme below, in the three independent molecules the bonds designated a are the same within experimental error. The same is true for each of the bonds labeled b-f and the average values are a = 1.323 (3) Å , b = 1.431 (3) Å , c = 1.447 (3) Å , d = 1.433 (3) Å , e = 1.226 (3) Å and f = 1.254 (3) Å . These compare quite favorably with those found in molecules with R = Me (Gilli et al., 2000) and 4-XC 6 H 4 (X = F, Cl, Br; Boulemche et al., 2019) and accompanied by in depth discussions of the RAHB.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions, a Hirshfeld surface (HS) analysis (Hirshfeld, 1977) was carried out using Crystal Explorer 17.5 (Turner et al., 2017). In the HS plotted over d norm (Fig. 4), the white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colors indicate distances shorter (in close contact) or longer (distinct contact) than the sum of the van der Waals radii, respectively (Venkatesan et al., 2016). The shape-index of the HS is a tool to visualizestacking by the presence of adjacent red and blue triangles; if there are no adjacent red and/or blue triangles, then there are nointeractions. Detail of the C OÁ Á Á(ring) stacking interactions (pink dashed lines) and the connection of stacks by C-HÁ Á ÁO hydrogen bonding (black dashed lines). Non-interacting H atoms are omitted for clarity.

Figure 4
View of the three-dimensional Hirshfeld surface of the title compound, plotted over d norm in the range À0.7208 to 1.5611 a.u.

Figure 5
Hirshfeld surface of the title compound plotted over shape-index.

Figure 6
The full two-dimensional fingerprint plots for the title compound  et al., 2007) are illustrated in Fig. 6 b-k, respectively, together with their relative contributions to the Hirshfeld surface. The most important interaction is HÁ Á ÁH contributing 49.0% to the overall crystal packing, which is reflected in Fig. 6b as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i = 1.09 Å . The pair of spikes in in the fingerprint plot delineated into HÁ Á ÁO/ OÁ Á ÁH contacts with a 28.3% contribution to the HS, Fig. 6c, has a symmetric distribution of points with the tips at d e + d i = 1.69 Å . In the presence of C-HÁ Á Á interactions, the pair of characteristic wings in the fingerprint plot delineated into HÁ Á ÁC/CÁ Á ÁH contacts, Fig. 6d, with a 10.9% contribution to the HS has the tips at d e + d i = 2.67 Å . The CÁ Á ÁC contacts, Fig. 6e, with a 6.2% contribution to the HS have a bulletshaped distribution of points and the tip at d e = d i = 1.64 Å . The symmetric distribution of points for the CÁ Á ÁO/OÁ Á ÁC contacts, Fig. 6f, with 3.8% contribution to the HS has a pair of the scattered points of spikes with the tips at d e + d i = 3.11 Å . Finally, the contributions of the remaining OÁ Á ÁO, NÁ Á ÁO/ OÁ Á ÁN, HÁ Á ÁN/NÁ Á ÁH, NÁ Á ÁN and CÁ Á ÁN/NÁ Á ÁC contacts ( Fig. 6g-k) are smaller than 1.0% with low densities of points.
The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the HÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH and HÁ Á ÁC/CÁ Á ÁH interactions in Fig. 7a-c, respectively. The Hirshfeld surface analysis confirms the importance of H-atom contacts in establishing the packing. The large number of HÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH and HÁ Á ÁC/CÁ Á ÁH interactions suggest that van der Waals interactions play the major role in the crystal packing (Hathwar et al., 2015).

DFT calculations
The optimized structure of the title compound in the gas phase was generated theoretically via density functional theory (DFT) using the standard B3LYP functional and 6-311 G(d,p) basis-set calculations (Becke, 1993) as implemented in GAUSSIAN 09 (Frisch et al., 2009). The theoretical and experimental results are in good agreement ( Table 2). The highest-occupied molecular orbital (HOMO), acting as an electron donor, and the lowest-unoccupied molecular orbital (LUMO), acting as an electron acceptor, are very important parameters for quantum chemistry. When the energy gap is small, the molecule is highly polarizable and has high chemical reactivity. The DFT calculations provide some important information on the reactivity and site selectivity of the molecular framework. E HOMO and E LUMO , which clarify the inevitable charge-exchange collaboration inside the molecule, electronegativity (), hardness (), potential (), electrophilicity (!) and softness () are recorded in Table 3. The significance of and is to evaluate both the reactivity and stability. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 8. The HOMO and LUMO are localized in the plane extending from the whole (E)-3-[1-(2-hydroxyphenylamino)ethylidene]-6-methyl-3Hpyran-2,4-dione ring. The energy band gap [ÁE = E LUMO À E HOMO ] of the molecule is 4.54 eV, and the frontier molecular orbital energies, E HOMO and E LUMO are À6.12 and À1.58 eV, respectively.

Molecular electrostatic (MEP)
Molecular electrostatic potential (MEP) was used to broadly predict reactive sites for electrophilic and nucleophilic attack  in the title compound by B3LYP/6-31G optimized geometries using Gaussview software (Frisch et al., 2009). The total electron density onto which the electrostatic potential surface has been mapped is shown in Fig. 9. This figure gives a visual representation of the chemically active sites and comparative reactivity of atoms where red regions denote the most negative electrostatic potential, blue represents regions of the most positive electrostatic potential, and green represents the region of zero potential. The distribution favors the existence of the intra and intermolecular C-HÁ Á ÁO and N-HÁ Á ÁO hydrogen bonding.

Synthesis and crystallization
To a solution of 2-aminophenol (2.5 mmol) in 30 mL of ethanol, 2.5 mmol of dehydroacetic acid were added. The mixture was refluxed for 1 h. After cooling, the precipitate that formed was recrystallized from ethanol solution to give yellow crystals in 88% yield. MEP surfaces mapped from the optimized geometries of the B3LYP/6-311 G calculation.

Figure 8
The energy band gap of the title compound.

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. 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. H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -0.98 Å) while those attached to nitrogen and to oxygen were placed in locations derived from a difference map and their parameters adjusted to give N-H = 0.91 and O-H = 0.87 Å. All were included as riding contributions with isotropic displacementparameters 1.2 -1.5 times those of the attached atoms.