Crystal structure and Hirshfeld surface analysis of (E)-3-(2-chloro-6-fluorophenyl)-1-(3-fluoro-4-methoxyphenyl)prop-2-en-1-one

In the title chalcone derivative, molecules are linked into a three-dimensional network by C—H⋯O hydrogen bonds and aromatic π–π stacking interactions are also observed. The intermolecular interactions in the crystal structure were quantified and analysed using Hirshfeld surface analysis.


Chemical context
Chalcone derivatives possess a wide range of biological properties such as antibacterial (Jarag et al., 2011), antiinflammatory (Mukherjee et al., 2001) and anti-oxidant (Arty et al., 2000) activities. As part of our ongoing studies on chalcone derivatives, we hereby report the synthesis and crystal structure of the title compound, (I).

Structural commentary
The molecular structure of (I) is shown in Fig. 1. The enone moiety (O1/C7-C9) adopts an E-conformation with respect to C7 C8 bond. The molecule is slightly twisted at the C9-- The structure of the title compound, showing 50% probability displacement ellipsoids. The intramolecular C-HÁ Á ÁF hydrogen bond is shown as a dashed line.

Figure 3
(a) d norm mapped on Hirshfeld surfaces for visualizing the intermolecular interactions of the title chalcone compound. (b) Hirshfeld surfaces mapped over the electrostatic potential. Dotted lines (green) represent hydrogen bonds.

Analysis of the Hirshfeld Surfaces
Crystal Explorer 3.1 (Wolff et al., 2012) was used to analyse the close contacts in the crystal of (I), which can be summarized with fingerprint plots mapped over d norm , electrostatic potential, shape index and curvedness. The electrostatic potentials were calculated using TONTO (Spackman et al., 2008;Jayatilaka et al., 2005) integrated within Crystal Explorer. The electrostatic potentials were mapped on Hirshfeld surfaces using the STO-3G basis set at Hartree-Fock level theory over a range AE0.03 au. The strong C-HÁ Á ÁO interactions are visualized as brightred spots between the respective donor and acceptor atoms on the Hirshfeld surfaces mapped over d norm (Fig. 3a) with neighbouring molecules connected by C2-H2AÁ Á ÁO1 and C3-H3AÁ Á ÁO2 hydrogen bonds. This finding is corroborated by Hirshfeld surfaces mapped over the electrostatic potential ( Fig. 3b) showing the negative potential around the oxygen atoms as light-red clouds and the positive potential around hydrogen atoms as light-blue clouds.
Significant intermolecular interactions are plotted in Fig. 4: the HÁ Á ÁH interactions appear as the largest region of the fingerprint plot with a high concentration in the middle region, shown in light blue, at d e = d i $1.4 Å ( Fig. 4a) with overall Hirshfeld surfaces of 27.5%. The contribution from the OÁ Á ÁH/HÁ Á ÁO contacts, corresponding to C-HÁ Á ÁO interactions, is represented by a pair of sharp spikes characteristic of a strong hydrogen-bond interaction having almost the same d e + d i $2.3 Å (Fig. 4b).
The CÁ Á ÁC contacts, which refer to -Á stacking interactions, contribute 13.7% of the Hirshfeld surfaces. This appears as a distinct triangle at around d e = d i $1.8 Å ( Fingerprint plots for the title chalcone compound, broken down into contributions from specific pairs of atom types. For each plot, the grey shadow is an outline of the complete fingerprint plot. Surfaces to the right highlight the relevant surface patches associated with the specific contacts, with d norm mapped in the same manner as Fig. 3a.

Figure 5
Hirshfeld surfaces mapped over the shape index of the title chalcone compound.

Figure 6
Hirshfeld surfaces mapped over curvedness of the title chalcone compound.
by the appearance of red and blue triangles on the shapeindexed surfaces, identified with black arrows in Fig. 5, and in the flat regions on the Hirshfeld surfaces mapped over curvedness in Fig. 6.

Synthesis and crystallization
A mixture of 3-fluoro-4-methoxyacetophenone (0.1 mol, 0.08 g) and 2-chloro-6-fluorobenzaldehyde (0.1 mol, 0.08 g) was dissolved in methanol (20 ml). A catalytic amount of NaOH (5 ml, 20%) was added to the solution dropwise with vigorous stirring. The reaction mixture was stirred for about 5-6 h at room temperature. After stirring, the contents of the flask were poured into ice-cold water (50 ml) and the resulting crude solid was collected by filtration. Brownish blocks of (I) were grown from an acetone solution by slow evaporation.

(E)-3-(2-Chloro-6-fluorophenyl)-1-(3-fluoro-4-methoxyphenyl)prop-2-en-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.