12-(3,4,5-Trimethoxyphenyl)-2,3,4,12-tetrahydro-1H-5-oxatetraphen-1-one: crystal structure and Hirshfeld surface analysis

The pyran and cyclohexene rings of the title compound adopt flattened-boat and envelope conformations, respectively. In the crystal, zigzag supramolecular chains are formed via aryl-C—H⋯O(methoxy) interactions.

In the title compound, C 26 H 24 O 5 , the pyran ring has a flattened-boat conformation, with the 1,4-related ether O and methine C atoms lying 0.1205 (18) and 0.271 (2) Å , respectively, above the least-squares plane involving the doubly bonded C atoms (r.m.s deviation = 0.0208 Å ). An envelope conformation is found for the cyclohexene ring, with the flap atom being the middle methylene C atom, lying 0.616 (2) Å out of the plane defined by the remaining atoms (r.m.s. deviation = 0.0173 Å ). The fused four-ring system is approximately planar, with the dihedral angle between the least-squares planes through the cyclohexene and naphthyl rings being 10.78 (7) . The trisubstituted benzene ring occupies a position almost perpendicular to the pyran ring [dihedral angle = 83.97 (4) ]. The most prominent feature of the packing is the formation of zigzag supramolecular chains mediated by aryl-C-HÁ Á ÁO(meth-O(methoxy) interactions; chains are connected into a three-dimensional architecture by methylene-and methyl-C-HÁ Á Á interactions. The prevalence of C-HÁ Á ÁO and C-HÁ Á Á interactions is confirmed by an analysis of the Hirshfeld surface. A comparison with related structures suggests that the molecular conformation of the title compound is relatively robust with respect to varying substitution patterns at the methine C atom of the pyran ring.

Chemical context
Xanthenes and benzoxanthenes are important bioactive compounds that possess a wide range of biological and therapeutic properties, such as analgesic (Hafez et al., 2008), antiviral and antibacterial and anti-inflammatory activities (Poupelin et al., 1978;Hideo & Teruomi, 1981;Asano et al., 1996;Matsumoto et al., 2005;Pinto et al., 2005;Woo et al., 2007;Pouli & Marakos, 2009). Some of these compounds have been used in photodynamic therapy (Ion, 1997). Further, due to their having desirable spectroscopic properties, some derivatives have been used as dyes in laser technologies (Menchen et al., 2003) and as pH-sensitive fluorescent materials for the visualization of biomolecules (Ahmad et al., 2002).
Various methods for the synthesis of tetrahydrobenzo[a]xanthen-11-ones have been reported (Knight & Stephens, 1989). These usually involve a three-component condensation of dimedone with an aromatic aldehyde and 2-naphthol. However, each of these procedures has some drawbacks, such as harsh reaction conditions, tedious work-up and low yields. Hence, the microwave-assisted ionic liquid-mediated synthesis of xanthenes from cyclohexane-1,3-dione, 3,4,5-trimethoxybenzaldehyde and 2-naphthol was attempted. The use of an ionic liquid, i.e. [1-butyl-3-methylimidazolium]PF 6 , and microwave irradiation afforded the title compound in high yield within 12 min (Iniyavan et al., 2015). The title compound is a potent anti-oxidant (Iniyavan et al., 2015) and herein its crystal and molecular structures are described, along with an analysis of its Hirshfeld surface in order to gain greater insight into the crystal packing, especially the role of weaker interactions.

Structural commentary
The central pyran ring in the title compound, (I), is flanked by both a cyclohexene ring and a naphthyl-fused ring system (Fig. 1). A trisubstituted benzene ring is connected to the aforementioned four-ring residue at the methine C7 atom. The pyran ring has a flattened boat conformation, with the 1,4related O1 and C7 atoms lying 0.1205 (18)  To a first approximation, the cyclohexene ring has an envelope conformation, with the C3 (flap) atom lying 0.616 (2) Å above the plane defined by the remaining atoms (r.m.s. deviation = 0.0173 Å ). The atoms comprising the four-ring system are approximately coplanar, as seen in the dihedral angle between the best plane through the cyclohexene ring and naphthyl residue of 10.78 (7) . The benzene ring occupies a position almost perpendicular to the previous residue, forming a dihedral angle of 83.97 (4) with the best plane through the pyran ring. In the benzene ring, two methoxy groups are coplanar with the ring to which they are connected [the C20 0 -O20-C20-C19 and C22 0 -O22-C22-C23 torsion angles are 4.98 (19) Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
The molecular packing in (I): (a) a view of the supramolecular chain along the a axis sustained by C-HÁ Á ÁO interactions shown as orange dashed lines and (b) the unit-cell contents shown in projection down the a axis with the C-HÁ Á Á(aryl) interactions shown as purple dashed lines.

Figure 1
The molecular structure of (I), showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.
Presumably, this conformation is adopted to reduce steric hindrance.

Supramolecular features
In the molecular packing of (I), supramolecular chains along the a axis are formed through the agency of relatively strong aryl-C16-H16Á Á ÁO(methoxy) interactions (Table 1). Being generated by glide symmetry, the topology of the chain is zigzag (Fig. 2a). The chains are connected into a threedimensional architecture by a network of C-HÁ Á Á(aryl) interactions ( Table 1). The donor atoms are derived from methylene and methyl groups, with the acceptor rings being each of the aromatic rings and with the outer benzene ring participating in two such contacts (Fig. 2b).

Hirshfeld surface analysis
With the aid of the program Crystal Explorer (Wolff et al., 2012), Hirshfeld surfaces mapped over d norm , d e , curvedness and electrostatic potential were generated. The electrostatic potential was calculated with TONTO (Spackman et al., 2008;Jayatilaka et al., 2005), integrated in Crystal Explorer, using the crystal structure as the starting geometry. The electrostatic potentials were mapped on the Hirshfeld surface using the STO-3G basis/Hartree-Fock level of theory over the range AE0.08 au. The contact distances d i and d e from the Hirshfeld surface to the nearest atom inside and outside, respectively, enables the analysis of the intermolecular interactions through the mapping of d norm . The combination of d e and d i in the form of a two-dimensional fingerprint plot (McKinnon et al., 2004) provides a convenient summary of the intermolecular contacts in the crystal. The bright-red spots at the aryl H16 and methoxy O20 atoms, visible on the Hirshfeld surface mapped over d norm and labelled as '1' in Fig. 3, represent the donor and acceptor atoms for the intermolecular C-HÁ Á ÁO interaction, respectively. On the surface mapped over electrostatic potential (Fig. 4), these interactions appear as the respective blue and red regions. The views of surfaces mapped over d norm , d e , electrostatic potential and shape-index (Figs. 3-6) highlight the significant role of C-HÁ Á Á interactions in the packing. In particular, the involvement of the methoxy C22 0 -H group in two C-HÁ Á Á interactions with the symmetry-related aryl rings (Table 1) are evident from the two faint-red spots near these atoms on the d norm mapped surface, indicated with '2' in Fig. 3.

Figure 4
Two views of Hirshfeld surfaces mapped over electrostatic potential for (I). The red and blue regions represent negative and positive electrostatic potentials, respectively. also evident from Fig. 4, through the appearance of respective blue and light-red regions near these atoms. The network of these C-HÁ Á Á interactions are also recognized through the pale-orange spots present on the Hirshfeld surfaces mapped over d e , highlighted within blue circles in Fig. 5, and as brightred spots over the front side of shape-indexed surfaces identified with arrows in Fig. 6. The reciprocal of these C-HÁ Á Á interactions, i.e. Á Á ÁH-C, are also seen as blue spots on the shape-indexed surface in Fig. 6. The faint-red spots near the phenyl C23 atom on the surface mapped over d norm , labelled as '3' in Fig. 3, indicate the presence of short interatomic CÁ Á ÁH/HÁ Á ÁC contacts in the crystal, Table 2.
The overall two-dimensional fingerprint plot (Fig. 7a) and those delineated (McKinnon et al., 2007) into HÁ Á ÁH, OÁ Á ÁH/ HÁ Á ÁO and CÁ Á ÁH/HÁ Á ÁC contacts are illustrated in Figs. 7(bd), respectively; their relative contributions are summarized in Table 3. The interatomic HÁ Á ÁH contacts at distances greater than their van der Waals separation appear as scattered points in the greater part of the fingerprint plot (Fig. 7b), and makes the most significant contribution to the overall Hirshfeld surface, i.e. 49.3%. In the fingerprint plot delineated into OÁ Á ÁH/HÁ Á ÁO contacts, a pair of short spikes at d e + d i $ 2.4 Å , and the cluster of blue points aligned in pairs with (d e + d i ) min $ 2.7 Å , identified with labels '1' and '2', respectively, in Fig. 7(c), corresponds to a 21.2% contribution to the Hirshfeld surface. These features reflect the presence of aryl-C16-H16Á Á ÁO(methoxy) interactions, as well as the short interatomic OÁ Á ÁH/HÁ Á ÁO contacts between carboxyl O2 and methylene H3B atoms ( Table 2).
The fingerprint plot delineated into CÁ Á ÁH/HÁ Á ÁC contacts, with a 28.1% contribution to the Hirshfeld surface, shows the points in the plot arranged in the form of two pairs of arrowlike shapes with their tips at d e + d i = 2.70 and 2.85 Å , labelled as '1' and '2' in Fig. 7(d), respectively. These features reflect the presence of C-HÁ Á Á interactions and short interatomic CÁ Á ÁH/HÁ Á ÁC contacts (Table 3) in the crystal. The absence of stacking interactions is consistent with their being no contribution from CÁ Á ÁC contacts to the Hirshfeld surface (Table 3) Views of Hirshfeld surface mapped over d e for (I). The pale-orange spots within blue circles indicate the involvement of aryl ring atoms in C-HÁ Á Á interactions.

Figure 6
Views of Hirshfeld surface mapped with the shape-index property for (I). The bright-red spots identified with arrows indicate the C-HÁ Á Á interactions, while the blue spots indicate complementary Á Á ÁH-C interactions.   Table 3 Percentage contribution of the different intermolecular interactions to the Hirshfeld surface of (I). The final analysis of the molecular packing involves a relatively new descriptor, i.e. the enrichment ratio (ER) (Jelsch et al., 2014); data are collated in Table 4. The involvement of surface H atoms in C-HÁ Á Á interactions and the presence of a number of interatomic CÁ Á ÁH contacts (Table 3) yields an ER value for HÁ Á ÁH contacts less than unity, i.e. 0.90. The presence of these interactions explains the enhanced ER value of 1.31 for CÁ Á ÁH/HÁ Á ÁC contacts, consistent with their high propensity to form in the molecular packing of (I). The O atoms comprise only 11.1% of the surface but provide a 21.2% contribution from OÁ Á ÁH/HÁ Á ÁO contacts to the Hirshfeld surface. Reflecting this, the ER value is 1.28, which is in the expected 1.2-1.6 range. Other contacts, namely CÁ Á ÁC, OÁ Á ÁO and CÁ Á ÁO/OÁ Á ÁC, show no propensity to form as reflected in their low ER values (Table 4).

Database survey
There are two structures in the crystallographic literature (Groom et al., 2016) featuring the methine-substituted 2,3,4,12-tetrahydro-5-oxatetraphen-1-one residue, as in (I). In the most closely related structure, (II) (Sethukumar et al., 2012), with a 2-chlorobenzene ring at the methine C7 atom, an essentially similar conformation is found, as emphasized in the overlay diagram shown in Fig. 8. Here, the dihedral angle between the best plane through the cyclohexene ring and naphthyl residue is 7.50 (6) , i.e. marginally less folded than in (I) where the angle was 10.78 (7) . The angle between the least-squares planes through the pyran and benzene rings is 89.71 (6) . Despite having a bulky 2-hydroxy-6-oxocyclohex-1enyl residue at the methine C7 atom, rather than an aryl ring, the conformation in (III) (Akkurt et al., 2013) bears a close resemblance to those of (I) and (II). Thus, in (III), the cyclohexene/naphthyl dihedral angle is 16.26 (5) , indicating a non-folded four-ring residue, and the pyran/cyclohexenyl dihedral angle is 85.57 (6) . Clearly, the non-folded conformation of the 2,3,4,12-tetrahydro-5-oxatetraphen-1-one core and its orthogonal relationship to the methine C7-bound substituent in (I)-(III) is to a first robust.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 5. Carbon-bound H atoms were placed in calculated positions (C-H = 0.95-1.00 Å ) and were included in the refinement in the riding model approximation, with U iso (H) set at 1.2-1.5U eq (C).