2-[(4-Chlorophenyl)selanyl]-3,4-dihydro-2H-benzo[h]chromene-5,6-dione: crystal structure and Hirshfeld analysis

A step-like conformation about the pyranyl ring is found for the molecular structure of the title compound. The three-dimensional packing is sustained by π–π, C—Cl⋯π and C—H⋯O interactions.


Chemical context
The natural product, -lapachone (see Scheme) can be isolated from the bark of the lapacho tree found in Central and South American countries (see: http://www.beta-lapachone.com/). It exhibits biological activities in the context of cancer (Park et al. 2014), being known to induce apoptotic cell-death pathways in a number of cancer cell lines, including breast cancer (Schaffner-Sabba et al., 1984), leukaemia (Chau et al., 1998) and prostate cancer (Li et al., 1995). In an allied application, -lapachone can be used as a sensitizer in radiotherapy on prostrate (Suzuki et al., 2006) and colon (Kim et al., 2005) cancer cells.
Compounds of the bio-essential element selenium, found in amino acids such as selenocysteine and selenomethionine, are known to hold potential as pharmaceutical agents (Tiekink, 2012), including in the realm of anti-cancer drugs (Seng & Tiekink, 2012). A key aspect of developing metal-based drugs is to incorporate a heavy element into the structure of a biologically active organic molecule and with this in mind, it was thought of interest to attempt to incorporate selenium into the structure of -lapachone. This was attempted by reacting lawsone, paraformaldehyde and (4-chlorophenyl)-(ethenyl)selane, as detailed in Synthesis and crystallization. Two major products were isolated, i.e. derivatives of -lapachone and -lapachone. The latter, hereafter (I), could be ISSN 2056-9890 crystallized and was subjected to an X-ray structure determination along with an analysis of its Hirshfeld surface in order to obtain more information on the molecular packing. The results of this study are reported herein.

Structural commentary
The substituted 2-pyranyl ring in (I) (Fig. 1) adopts a halfchair conformation with the C13 atom lying 0.620 (3) Å above the plane through the remaining five atoms (r.m.s. deviation = 0.0510 Å ). The 12 atoms comprising the naphthalene-1,2dione ring system are almost coplanar, with an r.m.s. deviation of 0.0152 Å . This plane forms a dihedral angle of 9.96 (9) with the chlorobenzene ring bound to the selanyl atom, indicating a near parallel disposition and a step-like arrangement between the aromatic substituents about the 2-pyranyl ring. An intramolecular SeÁ Á ÁO interaction of 2.8122 (13) Å is noted; this observation is discussed further in the Database survey.

Hirshfeld surface analysis
The Hirshfeld surfaces calculated on the structure of (I) also provide insight into the intermolecular interactions; the calculation was performed as in a recent publication (Jotani et al., 2016). The presence of bright-red spots appearing near the naphthyl-C7 and phenyl-C18 atoms on the Hirshfeld surface mapped over d norm in Fig. 3 are due to a short interatomic CÁ Á ÁC contact (see Table 2), significant in the crystal of (I). The absence of characteristic red spots near other atoms on the d norm -mapped Hirshfeld surface confirms the absence of conventional hydrogen bonds in the structure except for a weak C-HÁ Á ÁO interaction as given in  Table 1 Hydrogen-bond geometry (Å , ).

Figure 3
Two views of the Hirshfeld surface for (I) plotted over d norm in the range À0.032 to 1.401 au.
Contact distance symmetry operation  Views of Hirshfeld surfaces mapped over the shape-index about a reference molecule, showing (a) C-HÁ Á ÁO and short interatomic OÁ Á ÁH/ HÁ Á ÁO contacts by black and red dashed lines, respectively, (b)stacking interactions between naphthyl residues and between chlorobenzene and naphthyl rings by blue and yellow dotted lines, respectively and (c) C-ClÁ Á Á/Á Á ÁCl-C stacking contacts between chlorobenzene rings with black and blue dotted lines.  contacts (McKinnon et al., 2007) are illustrated in Fig. 6b-h, respectively; the relative contributions from the various contacts to the Hirshfeld surfaces are summarized in Table 3. The relatively low, i.e. 35.9%, contribution from HÁ Á ÁH contacts to the Hirshfeld surface of (I) is due to the low content of hydrogen atoms in the molecule and the involvement of some hydrogen atoms in short interatomic OÁ Á ÁH/ HÁ Á ÁO contacts (Tables 1 and 2). The single peak at d e + d i $2.3 Å in Fig. 6b is the result of a short interatomic HÁ Á ÁH contact ( Table 2). The intermolecular C-HÁ Á ÁO interaction in the crystal is recognized as the pair of peaks at d e + d i $2.6 Å in the OÁ Á ÁH/HÁ Á ÁO delineated fingerprint plot (Fig. 6c); the points arising from the short interatomic OÁ Á ÁH contacts are merged in the plot.
The fingerprint plot delineated into CÁ Á ÁC contacts, Fig. 6e, characterizes the twostacking interactions, one between inversion-related naphthyl rings, and the other between the chlorobenzene and (C2-C4/C9-C11) rings as the two overlapping triangular regions at around d e = d i $1.8 and 1.9 Å , respectively, having green points in the overlapping portion.
The presence of these twostacking interactions is also seen in the flat regions around the participating rings labelled with 1, 2 and 3 in the Hirshfeld surface mapped over curvedness in Fig. 7.
The chlorine atom on the benzene (C14-C19) ring makes a useful contribution to the molecular packing. The small, i.e. 3.0%, contribution from CÁ Á ÁCl/ClÁ Á ÁC contacts (Fig. 6g) to the Hirshfeld surface is the result of its involvement in a C-ClÁ Á Á contact formed between symmetry-related chlorobenzene atoms (Fig. 5c). Its presence is also clear from the fingerprint plot delineated into ClÁ Á ÁH/HÁ Á ÁCl (Fig. 6d), and ClÁ Á ÁO/OÁ Á ÁCl contacts (Fig. 6h). The contribution from CÁ Á ÁH/HÁ Á ÁC contacts (Fig. 6f) and other contacts (Table 3), including the selenium atom, have negligible influence on the packing as the interatomic separations are greater than sum of their respective van der Waals radii.

Database survey
There are three structures in the crystallographic literature (Groom et al., 2016)  View of the Hirshfeld surface mapped over curvedness highlighting the flat regions corresponding to the C2-C4/C9-C11, C3-C8 and C14-C19 rings, labelled as 1, 2 and 3, respectively, involved instacking interactions.  Table 4, there is no correlation between the SeÁ Á ÁO distance and the C-Se-C angle, consistent with the weak nature of these interactions.

Synthesis and crystallization
Referring to the reaction scheme, in a double-necked flask equipped with a magnetic bar and reflux condenser, under a nitrogen atmosphere, lawsone (1 mmol, 174 mg), paraformaldehyde (8 mmol, 240 mg), the vinyl selenide (1.5 mmol, 326 mg) and the ionic liquid 1-butyl-3-methylimidazolium chloride, [Bmim]Cl (1 mmol, 175 mg) were added over 1,4dioxane (2 ml). The reaction mixture was heated at 383 K and stirred over 2 h. The reaction mixture was cooled and diluted with dichloromethane (100 ml) and then washed with water (3 Â 50 ml). The organic phase was dried over Na 2 SO 4 , filtered and concentrated under vacuum. The crude product was purified in a silica gel-packed chromatography column, using ethyl acetate and hexane (2:8) as eluent to afford -lapachone and -lapachone (I) derivatives in 80% yield. Crystals of (I) were obtained by slow evaporation of a solvent mixture of hexane and ethyl acetate (8:2).

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 5. The carbon-bound H atoms were placed in calculated positions (C-H = 0.93-0.98 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2U eq (C).  Computer programs: APEX2 and SAINT (Bruker, 2009), SIR2014 (Burla et al., 2015), SHELXL2014 (Sheldrick, 2015), ORTEP-3 for Windows (Farrugia, 2012), DIAMOND (Brandenburg, 2006) and publCIF (Westrip, 2010). Table 4 Summary of SeÁ Á ÁO distances (Å ) and C-Se-C bond angles ( ) in (I)-(IV).  program(s) used to solve structure: SIR2014 (Burla et al., 2015); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010). 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.