2-[(4-Bromophenyl)sulfanyl]-2-methoxy-1-phenylethan-1-one: crystal structure, Hirshfeld surface analysis and computational chemistry

The title molecule is twisted about the methine-C—C(carbonyl) bond [the O—C—C—O torsion angle is −20.8 (7)°] and the dihedral angle between the bromobenzene and phenyl rings is 43.2 (2)°.


Chemical context
Recently, the crystal structure determination of the chloro analogue of the title compound was described (Caracelli et al., 2018). This was evaluated as a part of on-going studies into the conformational and electronic characteristics of various -thiocarbonyl, -bis-thiocarbonyl and -thio--oxacarbonyl compounds, and their selenium counterparts, employing infrared spectroscopy, computational chemistry and X-ray crystallographic methods (Vinhato et al., 2013;Zukerman-Schpector et al., 2015;Caracelli et al., 2015;Traesel et al., 2018). In particular, the evaluation of the anti-inflammatory activity of what could be selective COX-2 inhibitors (Cerqueira et al., 2017) motivates these investigations, which are supported by molecular docking studies designed to ascertain the mechanism(s) of inhibition (Baptistini, 2015). Subsequently, crystals of the title bromo analogue (I) were obtained: the crystal structure is reported herein along with an analysis of the calculated Hirshfeld surfaces, non-covalent interaction plots (for selected interactions) as well as a computational chemistry study. ISSN 2056-9890

Structural commentary
The molecular structure of (I), Fig. 1, is isostructural with the previously described chloro analogue, (II) (Caracelli et al., 2018). Here, the central chiral methine-C8 atom is connected to (4-bromophenyl)sulfanyl, phenylethanone and methoxy groups. There is a twist in the ethanone residue as seen in the value of the O1-C8-C9-O2 torsion angle of À20.8 (7) , with the oxygen atoms being approximately syn. The dihedral angle between the bromobenzene and phenyl rings is 43.2 (2) , indicative of an inclined relative disposition. Globally, the bromobenzene ring is orientated towards the ethanone residue.
The geometric parameters in (I) can be compared with those of (II): the twist about the central C8-C9 bond is approximately the same in (II), i.e. the the O1-C8-C9-O2 torsion angle is 19.3 (7) , as is the dihedral angle of 42.9 (2) between the aromatic rings. The overlay diagram in Fig. 2 highlights the close similarity between the molecular structures of (I) and (II).

Supramolecular features
The main feature of the molecular packing of (I) is the presence of C-HÁ Á ÁO interactions where the carbonyl-O2 atom accepts two contacts from methyl-C7-H and methine-C8-H atoms derived from the same molecule to generate sixmembered {Á Á ÁOÁ Á ÁHCOCH} synthons, Table 1. The result is a supramolecular chain propagating along [001] with an helical topology (2 1 symmetry), Fig. 3(a). The chains pack without directional interactions between them, Fig. 3 Overlay diagram of (I) (red image) and (II) (blue image).

Figure 1
The molecular structure of (I), showing the atom-labelling scheme and displacement ellipsoids at the 25% probability level.

Hirshfeld surface analysis
The Hirshfeld surface calculations for (I) were performed in accord with protocols described recently (Tan et al., 2019) employing Crystal Explorer (Turner et al., 2017). Over and above the analysis of the important surface contacts in the crystal of (I), the results are compared with those for the recently determined isostructural chloro analogue (II) (Caracelli et al., 2018). The crystal of (I) has similar intermolecular C-HÁ Á ÁO interactions (Table 1) and short interatomic HÁ Á ÁH, CÁ Á ÁH and CÁ Á ÁC contacts (Table 2) as in isostructural (II), as detailed below.
The intermolecular contacts in (I), Tables 1 and 2, are characterized as the pair of bright-red spots near the carbonyl-O2 atom, and each of the methyl-H7A and methine-H8 atoms on the Hirshfeld surfaces mapped over d norm in the images of  Table 2 Summary of short interatomic contacts (Å ) in (I) and (II).

Figure 5
Two views of the Hirshfeld surface for (I) mapped over the electrostatic potential in the range À0.074 to + 0.053 atomic units. The red and blue regions represent negative and positive electrostatic potentials, respectively.
near the methyl-H7B and H7C, phenyl-H14, bromobenzene-C6 and carbonyl-C9 atoms in Fig. 4. On the Hirshfeld surfaces mapped over the calculated electrostatic potential in the images of Fig. 5, the donors and acceptors of intermolecular interactions are viewed as blue and red regions around the participating atoms corresponding to positive and negative potentials, respectively. The environment around a reference molecule within the d norm -mapped Hirshfeld surface high-lighting the intermolecular C-HÁ Á ÁO interactions and short interatomic HÁ Á ÁH, CÁ Á ÁH/HÁ Á ÁC and CÁ Á ÁC contacts is illustrated in Fig. 6. From the overall two-dimensional fingerprint plot in Fig. 7(a), and also those delineated into HÁ Á ÁH, OÁ Á ÁH/HÁ Á ÁO, CÁ Á ÁH/HÁ Á ÁC, CÁ Á ÁC and BrÁ Á ÁH/HÁ Á ÁBr contacts in Fig. 7(b)-(f), respectively, it is evident that the plots are basically identical in shape to those calculated for the chloro analogue (II) with only slight differences in the distribution of points (Caracelli et al., 2018). The percentage contributions from the different interatomic contacts to the Hirshfeld surfaces of (I) and (II) are summarized in Table 3; these values again highlight the similarities between (I) and (II).
The C-HÁ Á ÁO contacts significant in the crystal of (I), Table 1, are represented as the pair of spikes at d e + d i $2.3 Å in the fingerprint plot delineated into OÁ Á ÁH/HÁ Á ÁO contacts, Fig. 7(c). The short interatomic HÁ Á ÁH, CÁ Á ÁH/HÁ Á ÁC and CÁ Á ÁC contacts (Table 2) are characterized as pair of beakshape tips at d e + d i $2.1 Å , Fig. 7(b), and forceps at d e + d i $2.8 Å , Fig. 7(d), and vase-shaped distribution of points at d e + d i $3.3 Å , Fig. 7(e), in the respective delineated fingerprint plots. In addition to these contacts, the crystal also features short interatomic BrÁ Á ÁH/HÁ Á ÁBr contacts appearing as the pair of forceps-like tips at d e + d i $3.0 Å in the delineated fingerprint plot of Fig. 7(f). The small contribution from other remaining interatomic contacts summarized in Table 3 have a negligible effect on the packing.

Interaction energies
The pairwise interaction energies between the molecules within the crystal are calculated by the summation of four energy components comprising electrostatic (E ele ), polarization (E pol ), dispersion (E dis ) and exchange-repulsion (E rep ) (Turner et al., 2017). These energies were obtained by using the wave function calculated at the HF/STO-3G level theory for each of (I) and (II). The individual energy components as well as total interaction energy relative to reference molecule within the molecular cluster were calculated. Table 4 summarizes quantitatively the strength and nature of intermolecular interactions in the crystals of (I) and (II).    It is observed from the interaction energies calculated between the reference molecule and the symmetry-related molecules at R = 6.40 and 6.13 Å (where R is the separation of the centres of gravity of the molecules), respectively (Table 4), that the almost identical values of the electrostatic energy component are due to intermolecular C-HÁ Á ÁO interactions whereas the dispersive components are dominant owing to the short interatomic contacts between the same molecules. The other short interatomic CÁ Á ÁH/HÁ Á ÁC contact between the methyl-H7C and phenyl-C6 atoms in (I) and (II), and the H12Á Á ÁBr1 contact in (I) have a major contribution from dispersion components.
The magnitudes of intermolecular energies are represented graphically in the energy frameworks for (I) and (II) viewed down the c axes are shown in Fig. 8. Here, the supramolecular architecture of the crystals is represented as cylinders joining centroids of molecular pairs. The red, green and blue coloration represent the energy components E ele , E disp and E tot , respectively. The radius of the cylinder is proportional to the magnitude of interaction energy which are adjusted to the same scale factor (3 kJ mol À1 ) within 4 Â 4 Â 4 unit cells. From the energy frameworks for (I) and (II) illustrated in Fig. 8, it is clearly evident that the supramolecular associations viewed down the c axis are identical, reflecting the isostructural relationship between (I) and (II).

Non-covalent interaction plots
The non-covalent interaction plot (NCIplot) analysis was used in the present study in order to confirm the attractive nature of some of the specified intermolecular contacts (Contreras-García et al., 2011). This method is based on the electron density and its derivatives allowing the visualization of the gradient isosurfaces. The colour-based isosurfaces correspond to the values of sign( 2 )(r), where is the electron density and 2 is the second eigenvalue of the Hessian matrix of (Johnson et al., 2010). The isosurfaces for the interactions A comparison of the energy frameworks, plotted with the same scale, composed of (a) electrostatic potential force, (b) dispersion force and (c) total energy for the molecules of (I), upper images, and (II), lower images, all viewed down the c-axis direction. same scale factor of 50 with a cut-off value of 3 kJ mol À1 within 4 x 4 x 4 unit cells. Table 4 Summary of interaction energies (kJ mol À1 ) calculated for (I) and (II). Notes: Symmetry operations: (i) 1 À x, 1 À y, À 1 2 + z; (ii) 1 À x, 2 À y, 1 2 + z; (iii) 1 À x, À y, 1 2 + z; (iv) 1 À x, 1 À y, 1 2 + z.
between the carbonyl-O2 and each of the methyl-H7B and phenyl-H14 atoms, the H7B and H14 atoms, and the chlorobenzene-C6 and methyl-H7C atoms are shown in the upper views of Fig. 9(a)-(c), respectively. The green isosurface observed in each of these indicates a weakly attractive interaction as opposed to attractive (blue isosurface) or repulsive (red). The lower views of Fig. 9, where the plots of the RDG versus sign( 2 )(r) are depicted, the non-covalent interaction peaks appear at density values equal or lower than 0.01 a.u., consistent with weakly attractive interactions.  (III). This comes about owing to a twist about the C8-S1 bond as manifested in the C4-S1-C8-C9 torsion angles of 57.1 (4), 57.3 (5), 46.6 (3) and 57.9 (3) for (I)-(IV), respectively. This difference notwithstanding, the angles between the S-bound benzene rings and the phenyl rings in (I)-(IV) span a relatively narrow range of values, i.e. 43.2 (2), 42.9 (2), 40.11 (16) and 44.03 (16) , respectively.

Synthesis and crystallization
Firstly, 4 0 -bromothiophenol (10.0 g, 52.9 mmol) was reacted with bromine (3.1 ml, 56.0 mmol) in dichloromethane (400 ml) on a hydrated silica gel support (50 g of SiO 2 and water (30 ml) to give 4 0 -bromophenyl disulfide (8.0 g, yield 80%). A brown solid was obtained after filtration and evaporation without further purification (Ali & McDermott, 2002 (Zoretic & Soja, 1976). After stirring for 3 h, water (70 ml) was added at room temperature and extraction with diethyl ether ensued. The organic layer was then treated with a saturated solution of ammonium chloride until neutral pH was reached and then dried over anhydrous magnesium sulfate. A brown oil was obtained after evaporation of the solvent. Purification through flash chromatography with n-hexane was used in order to remove the non-polar reactant (disulfide), then with dry acetone to give a mixture of both acetophenones (product and reactant). Crystallization was performed by vapour diffusion of n-hexane into a chloroform solution held at 283 K to give the pure product (0.6 g, yield = 70%). Irregular colourless crystals suitable for X-ray diffraction of (I) were obtained by the same pathway. Non-covalent interaction plots for intermolecular interactions between (a) each of the methyl-C7-and methine-C-H atoms and the carbonyl-O2 atom, (b) the methyl-H7B and phenyl-H14 atoms and (c) bromobenzene-C6 and methyl-H7C atoms.

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 1.2-1.5U eq (C). The absolute structure was determined based on differences in Friedel pairs included in the data set (Parsons et al., 2013).

2-[(4-Bromophenyl)sulfanyl]-2-methoxy-1-phenylethan-1-one
Crystal data 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.