(2E,6E)-2,6-Bis(2,5-difluorobenzylidene)cyclohexanone

In the title compound, C20H14F4O, a derivative of curcumin, the dihedral angle between the two aromatic rings is 27.19 (13)°. The C=C double bonds have an E configuration.

In the title compound, C 20 H 14 F 4 O, a derivative of curcumin, the dihedral angle between the two aromatic rings is 27.19 (13) . The C C double bonds have an E configuration.

Comment
The title compound, (2E,6E)-2,6-bis(2,5-difluorobenzylidene)cyclohexanone (I), is one of mono-carbonyl analogues of curcumin designed and synthesized by our group. The need for curcumin-like compounds with improved bioavailability characteristics has led to the chemical synthesis of a series of analogues, using curcumin as the primary structure. In our previous study, a series of fluorine-containing, mono-carbonyl analogues of curcumin were designed and synthesized by the deletion of β-diketone moiety, and their bioactivities were evaluated Zhao et al., 2010a,b). Among those compounds, the cyclohexanone-containing analogues exhibited better anti-tumor properties and a wider anti-tumor spectrum than acetone-and cyclopentanone-containing analogues. Therefore, the structure of one of cyclohexanone-containing compounds (I), was further determined and analyzed using single-crystal X-ray diffraction. Accumulation of detailed structural and pharmacological data facilitated the explanation of the observed structure-activity relationships and modeling of new compounds with potential biological activity.
In this paper, we report the molecular and crystal structures of fluorine-containing, mono-carbonyl analogues of curcumin, (I). The molecule (I), consists of three ring systems, i.e., one cyclohexanone ring and two aryl rings. The central cyclohexanone ring has a distorted chair conformation, and molecular structures have an E-configuration towards the central olefinic bonds, exhibiting a butterfly-shaped geometry. The dihedral angle between the two terminal phenyl rings is 27.19 (13)°, and the two phenyl rings are twisted out of the plane of the central cyclohexanone on the two sides, respectively. Among these derivatives, some of them were reported of their crystal structures (Liang et al., 2007a,b;Zhao et al., 2009;Zhao et al., 2010a,b).
Experimental Cyclohexanone (7.5 mmol) was dissolved in ethanol (5 ml) and crushed KOH (15 mmol) was added. The flask was immersed in a bath of crushed ice and a solution of 2,5-difluorobenzaldehyde (15 mmol) in ethanol (5 mmol) was added. The reaction mixture was stirred at 300 K and completion of the reaction was monitored by thin-layer chromatography. Ice-cold water was added to the reaction mixture after 48 h and the yellow solid that separated was filtered off, washed with water and cold ethanol, dried and purified by column chromatography on silica gel (yield: 45.3%). Single crystals of the title compound were grown in a CH 2 Cl 2 /CH 3 OH mixture (5:2 v/v) by slow evaporation (mp 132-135.4 K).

Refinement
The H atoms were positioned geometrically (C-H = 0.93 and 0.96 Å) and refined as riding with U iso (H) = 1.2U eq (C) or 1.5U eq (methyl C). Fig. 1

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.