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Acta Cryst. (2011). E67, o758    [ doi:10.1107/S1600536811007070 ]

(1E,4E)-1,5-Bis(2,6-difluorophenyl)penta-1,4-dien-3-one

J.-D. Huang, Q.-Q. Tang, X.-Y. Chen, Y. Ye and Y. Wang

Abstract top

The molecule of the title compound, C17H10F4O, is roughly planar, with a dihedral angle of 5.59 (14)° between the two phenyl rings. The molecule has an E conformation with respect to the olefinic bonds. In the crystal, molecules are connected through C-H...O hydrogen bonds and there is slipped [pi]-[pi] stacking [centroid-centroid distance = 3.7983 (18), slippage =1.309 ;Å] between symmetry-related benzene rings.

Comment top

The title compound, (1E,4E)-1,5-bis (2,6-difluorophenyl) penta-1,4-dien-3-one (I), is one of mono-carbonyl analogues of curcumin designed and synthesized by our group.Curcumin (diferuloylmethane ) is the main component of turmeric, the powdered root of Curcuma longa Linn. Traditionally, curcumin has been used as a medicine for liver disease, indigestion, urinary tract diseases, rheumatoid arthritis, and insect bites (Aggarwal et al., 2007; Kamat et al., 2009). The pharmacological safety of curcumin has been demonstrated by its consumption for centuries at levels of up to 100 mg/day by people in certain countries (Pan et al., 1999). One potential problem with the clinical use of curcumin is its low bioavailability and poor absorption characteristics ( Sharma et al., 2007); however, curcumin remains an ideal leading compound for design of some effective analogues. 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 (Liang et al., 2009; Zhao et al., 2010a,b). Among those compounds, some analogues exhibited better anti-tumor properties and a wider anti-tumor spectrum than curcumin. As a continuation of our broad program of work on the synthesis and structural study of curcumin analogues, the title curcumin derivative has been obtained and an X-ray diffraction study was carried out. Therefore, the structure of one of 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.

The molecule (I), consists of two 2,6-difluoophenyl rings linked through a penta-1,4-dien-3-one chain (Fig. 1). The molecule displays an E conformation with respect to the olefinic bonds, exhibiting a butterfly-shaped geometry. The whole molecule is roughly planar with a dihedral angle between the two terminal phenyl rings of 5.59 (14)°. Among these derivatives, the structures of some of them were reported ( Liang et al., 2007; Zhao et al., 2009; Zhao et al., 2010a,b).

In the crystal, the molecule are connected through C-H···O hydrogen bonds and slippest π-π stacking between symmetry related phenyl rings (Tables 1 and 2, Fig. 2).

Related literature top

The title compound is a derivative of the biologically active compound curcumin [systematic name (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione]. For the biological activity and applications of curcumin, see: Aggarwal et al. (2007); Kamat et al. (2009); Liang et al. (2009); Pan et al. (1999); Sharma et al. (2007); Zhao et al. (2010a,b). For related structures, see: Zhao et al. (2009); Liang et al. (2007).

Experimental top

Acetone (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 2,6-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: 49.3%). Single crystals of the title compound were grown in a CH2Cl2/CH3OH mixture (5:2 v/v) by slow evaporation .

Yellow powder, 49.3% yield, mp 135-138°C. 1H-NMR (CDCl3) δ: 6.95 (4H, t, Ar-H3,5×2), 7.29 (2H, d, J=18.0Hz, =CH-C=O×2), 7.31-7.36 (2H, m, Ar-H4×2), 7.81 (2H, d, J=18.0Hz, Ar-CH=C×2). ESI-MS m/z: 307.7 (M+1)+ 329.6 (M+Na) 635.3 (2M+Na), calcd for C17H10F4O: 306.25.

Refinement top

The H atoms were positioned geometrically (C—H = 0.93 and 0.96 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C).

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with the atom labeling scheme. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms are represented as small spheres of arbitrary radii.
[Figure 2] Fig. 2. Partial packing view showing the C-H···O hydrogen bonds and the π-π stacking. H atoms not involved in hydrogen bondings have been omitted for clarity. Hydrogen bonds are shown as dashed lines. [Symmetry codes: (i) -x+3/2, y+1/2, -z+1/2; (ii) -x+1/2, y-1/2, -z+1/2]
(1E,4E)-1,5-Bis(2,6-difluorophenyl)penta-1,4-dien-3-on top
Crystal data top
C17H10F4OF(000) = 624
Mr = 306.25Dx = 1.443 Mg m−3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 1937 reflections
a = 7.7522 (11) Åθ = 5.3–44.2°
b = 15.413 (2) ŵ = 0.13 mm−1
c = 12.2848 (17) ÅT = 293 K
β = 106.194 (2)°Prismatic, green
V = 1409.6 (3) Å30.40 × 0.37 × 0.23 mm
Z = 4
Data collection top
Bruker SMART CCD area-detector
diffractometer		2622 independent reflections
Radiation source: fine-focus sealed tube1612 reflections with I > 2σ(I)
graphiteRint = 0.111
φ and ω scansθmax = 25.5°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2002)		h = −9→8
Tmin = 0.640, Tmax = 1.000k = −10→18
7288 measured reflectionsl = −13→14
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.063Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.174H-atom parameters constrained
S = 0.94 w = 1/[σ2(Fo2) + (0.0971P)2]
where P = (Fo2 + 2Fc2)/3
2622 reflections(Δ/σ)max < 0.001
199 parametersΔρmax = 0.27 e Å−3
0 restraintsΔρmin = −0.24 e Å−3
Crystal data top
C17H10F4OV = 1409.6 (3) Å3
Mr = 306.25Z = 4
Monoclinic, P21/nMo Kα radiation
a = 7.7522 (11) ŵ = 0.13 mm−1
b = 15.413 (2) ÅT = 293 K
c = 12.2848 (17) Å0.40 × 0.37 × 0.23 mm
β = 106.194 (2)°
Data collection top
Bruker SMART CCD area-detector
diffractometer		2622 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2002)		1612 reflections with I > 2σ(I)
Tmin = 0.640, Tmax = 1.000Rint = 0.111
7288 measured reflectionsθmax = 25.5°
Refinement top
R[F2 > 2σ(F2)] = 0.063H-atom parameters constrained
wR(F2) = 0.174Δρmax = 0.27 e Å−3
S = 0.94Δρmin = −0.24 e Å−3
2622 reflectionsAbsolute structure: ?
199 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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 F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.1321 (2)−0.05696 (10)−0.13761 (11)0.0953 (6)
F20.2040 (3)−0.14772 (13)0.23505 (14)0.1253 (7)
F30.4725 (3)0.31282 (12)−0.12340 (13)0.1193 (7)
F40.7788 (3)0.37861 (11)0.25107 (15)0.1277 (7)
O10.4636 (3)0.11929 (12)0.21918 (15)0.0902 (6)
C10.4216 (3)0.12103 (15)0.1155 (2)0.0650 (6)
C20.3222 (3)0.04845 (15)0.0490 (2)0.0651 (6)
H20.29250.0506−0.02970.078*
C30.2739 (3)−0.01982 (16)0.09889 (19)0.0665 (6)
H30.3101−0.01800.17770.080*
C40.1752 (3)−0.09625 (15)0.05189 (18)0.0625 (6)
C50.1051 (3)−0.11493 (15)−0.06245 (19)0.0654 (6)
C60.0106 (3)−0.18811 (17)−0.1029 (2)0.0761 (7)
H6−0.0336−0.1970−0.18060.091*
C7−0.0187 (4)−0.24790 (18)−0.0290 (3)0.0816 (8)
H7−0.0837−0.2979−0.05610.098*
C80.0473 (4)−0.23481 (19)0.0854 (3)0.0908 (8)
H80.0285−0.27550.13680.109*
C90.1404 (4)−0.16122 (19)0.1214 (2)0.0793 (7)
C100.4659 (3)0.19589 (16)0.0545 (2)0.0672 (6)
H100.42520.1973−0.02420.081*
C110.5625 (3)0.26144 (16)0.10904 (19)0.0657 (6)
H110.59790.25610.18760.079*
C120.6217 (3)0.33956 (16)0.06650 (19)0.0652 (6)
C130.5821 (3)0.36416 (17)−0.0465 (2)0.0776 (7)
C140.6445 (4)0.4382 (2)−0.0837 (3)0.0964 (9)
H140.61240.4518−0.16050.116*
C150.7535 (4)0.4915 (2)−0.0071 (3)0.0980 (9)
H150.79770.5417−0.03160.118*
C160.7993 (4)0.4721 (2)0.1059 (3)0.1009 (9)
H160.87410.50860.15880.121*
C170.7330 (3)0.39840 (19)0.1388 (2)0.0832 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.1352 (13)0.0939 (11)0.0506 (8)−0.0214 (9)0.0155 (8)0.0034 (7)
F20.1765 (17)0.1274 (15)0.0600 (10)−0.0324 (12)0.0129 (10)0.0212 (9)
F30.1636 (15)0.1215 (14)0.0553 (9)−0.0532 (12)0.0018 (10)0.0006 (9)
F40.1733 (17)0.1124 (14)0.0678 (11)−0.0292 (12)−0.0153 (10)−0.0118 (10)
O10.1242 (15)0.0820 (13)0.0543 (11)−0.0036 (10)0.0084 (10)−0.0012 (8)
C10.0676 (14)0.0680 (15)0.0553 (14)0.0125 (11)0.0102 (11)−0.0008 (11)
C20.0719 (14)0.0696 (15)0.0512 (13)0.0085 (11)0.0131 (11)−0.0007 (11)
C30.0693 (14)0.0775 (17)0.0506 (13)0.0115 (12)0.0134 (11)0.0023 (12)
C40.0636 (13)0.0656 (14)0.0564 (14)0.0099 (11)0.0138 (10)0.0024 (11)
C50.0739 (14)0.0653 (15)0.0564 (14)0.0119 (12)0.0175 (11)0.0070 (11)
C60.0829 (16)0.0755 (17)0.0668 (16)0.0058 (14)0.0154 (13)−0.0075 (13)
C70.0841 (17)0.0689 (17)0.093 (2)0.0029 (13)0.0272 (16)−0.0040 (15)
C80.107 (2)0.0768 (19)0.093 (2)0.0019 (16)0.0336 (18)0.0170 (16)
C90.0933 (18)0.0828 (19)0.0561 (15)0.0050 (15)0.0114 (13)0.0086 (13)
C100.0671 (14)0.0771 (17)0.0525 (13)0.0059 (12)0.0088 (11)−0.0050 (12)
C110.0675 (13)0.0731 (16)0.0518 (13)0.0063 (12)0.0087 (11)−0.0052 (11)
C120.0629 (13)0.0707 (16)0.0588 (14)0.0052 (11)0.0118 (11)−0.0061 (11)
C130.0811 (16)0.0853 (18)0.0611 (15)−0.0131 (14)0.0109 (12)−0.0040 (13)
C140.111 (2)0.096 (2)0.0788 (19)−0.0156 (18)0.0214 (17)0.0115 (16)
C150.099 (2)0.082 (2)0.112 (3)−0.0120 (16)0.0258 (19)0.0076 (18)
C160.094 (2)0.081 (2)0.112 (3)−0.0177 (17)0.0032 (18)−0.0135 (18)
C170.0870 (17)0.0844 (19)0.0655 (17)−0.0005 (15)0.0004 (13)−0.0089 (14)
Geometric parameters (Å, °) top
F1—C51.342 (3)C7—H70.9300
F2—C91.361 (3)C8—C91.351 (4)
F3—C131.339 (3)C8—H80.9300
F4—C171.360 (3)C10—C111.323 (3)
O1—C11.224 (3)C10—H100.9300
C1—C101.468 (3)C11—C121.438 (3)
C1—C21.470 (3)C11—H110.9300
C2—C31.323 (3)C12—C131.388 (3)
C2—H20.9300C12—C171.389 (3)
C3—C41.436 (3)C13—C141.367 (4)
C3—H30.9300C14—C151.353 (4)
C4—C51.388 (3)C14—H140.9300
C4—C91.390 (4)C15—C161.367 (4)
C5—C61.361 (3)C15—H150.9300
C6—C71.357 (4)C16—C171.354 (4)
C6—H60.9300C16—H160.9300
C7—C81.370 (4)
O1—C1—C10121.1 (2)F2—C9—C4116.3 (2)
O1—C1—C2120.5 (2)C11—C10—C1121.5 (2)
C10—C1—C2118.4 (2)C11—C10—H10119.3
C3—C2—C1121.3 (2)C1—C10—H10119.3
C3—C2—H2119.3C10—C11—C12130.4 (2)
C1—C2—H2119.3C10—C11—H11114.8
C2—C3—C4130.9 (2)C12—C11—H11114.8
C2—C3—H3114.6C13—C12—C17112.7 (2)
C4—C3—H3114.6C13—C12—C11126.0 (2)
C5—C4—C9112.6 (2)C17—C12—C11121.2 (2)
C5—C4—C3126.3 (2)F3—C13—C14118.1 (2)
C9—C4—C3121.1 (2)F3—C13—C12117.6 (2)
F1—C5—C6118.1 (2)C14—C13—C12124.2 (3)
F1—C5—C4117.8 (2)C15—C14—C13119.0 (3)
C6—C5—C4124.1 (2)C15—C14—H14120.5
C7—C6—C5119.4 (3)C13—C14—H14120.5
C7—C6—H6120.3C14—C15—C16120.6 (3)
C5—C6—H6120.3C14—C15—H15119.7
C6—C7—C8120.2 (3)C16—C15—H15119.7
C6—C7—H7119.9C17—C16—C15118.3 (3)
C8—C7—H7119.9C17—C16—H16120.9
C9—C8—C7118.2 (3)C15—C16—H16120.9
C9—C8—H8120.9C16—C17—F4118.5 (3)
C7—C8—H8120.9C16—C17—C12125.2 (3)
C8—C9—F2118.1 (2)F4—C17—C12116.2 (3)
C8—C9—C4125.5 (3)
O1—C1—C2—C30.7 (3)O1—C1—C10—C114.4 (3)
C10—C1—C2—C3−178.2 (2)C2—C1—C10—C11−176.71 (19)
C1—C2—C3—C4178.8 (2)C1—C10—C11—C12179.4 (2)
C2—C3—C4—C5−0.4 (4)C10—C11—C12—C132.2 (4)
C2—C3—C4—C9179.5 (2)C10—C11—C12—C17−175.9 (2)
C9—C4—C5—F1−179.4 (2)C17—C12—C13—F3−178.6 (2)
C3—C4—C5—F10.5 (3)C11—C12—C13—F33.1 (4)
C9—C4—C5—C60.8 (3)C17—C12—C13—C14−0.2 (4)
C3—C4—C5—C6−179.3 (2)C11—C12—C13—C14−178.5 (2)
F1—C5—C6—C7179.9 (2)F3—C13—C14—C15179.2 (3)
C4—C5—C6—C7−0.2 (4)C12—C13—C14—C150.8 (5)
C5—C6—C7—C8−0.3 (4)C13—C14—C15—C16−0.7 (5)
C6—C7—C8—C90.3 (4)C14—C15—C16—C170.1 (5)
C7—C8—C9—F2179.2 (2)C15—C16—C17—F4179.7 (3)
C7—C8—C9—C40.4 (4)C15—C16—C17—C120.5 (5)
C5—C4—C9—C8−0.9 (4)C13—C12—C17—C16−0.4 (4)
C3—C4—C9—C8179.2 (2)C11—C12—C17—C16177.9 (3)
C5—C4—C9—F2−179.7 (2)C13—C12—C17—F4−179.6 (2)
C3—C4—C9—F20.4 (3)C11—C12—C17—F4−1.3 (4)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C16—H16···O1i0.932.383.307 (4)171
C8—H8···O1ii0.932.393.308 (3)170
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+1/2, y−1/2, −z+1/2.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C16—H16···O1i0.932.383.307 (4)171
C8—H8···O1ii0.932.393.308 (3)170
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+1/2, y−1/2, −z+1/2.
Table 2
Table 2 π-π stacking interactions (Å) top
Cg1 is the centroid of the C12-C17 ring.
CgICgJCgI···CgJaCgI···P(J)bCgJ···P(I)cSlippage
Cg1Cg1iii3.7983 (18)3.5656 (12)3.5656 (12)1.309
Symmetry codes: (iii)1-x,1-y,-z Notes: a : Distance between centroids b : Perpendicular distance of CgI on ring plan J. c : Perpendicular distance of CgJ on ring plan I. Slippage = vertical displacement between ring centroids.
Acknowledgements top

The use of the X-ray crystallographic service at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, and the valuable assistance of the staff there is gratefully acknowledged.

references
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