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

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

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

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 π–π stacking [centroid–centroid distance = 3.7983 (18), slippage =1.309 ;Å] between symmetry-related benzene rings.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536811007070/dn2659sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536811007070/dn2659Isup2.hkl Contains datablock I

CCDC reference: 759058

checkCIF report

Key indicators

Single-crystal X-ray study
T = 293 K
Mean (C-C) = 0.004 Å
R factor = 0.063
wR factor = 0.174
Data-to-parameter ratio = 13.2

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C13
PLAT334_ALERT_2_C Small Average Benzene  C-C Dist. C4     -C9            1.37 Ang.
PLAT334_ALERT_2_C Small Average Benzene  C-C Dist. C12    -C17           1.37 Ang.

Alert level G
PLAT128_ALERT_4_G Alternate Setting of Space-group P21/c   .......      P21/n
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported   _diffrn_ambient_temperature        293 K

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   3 ALERT level G = General information/check it is not something unexpected

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   3 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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-H^3,5×2), 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.

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

	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.
	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

C₁₇H₁₀F₄O	F(000) = 624
M_r = 306.25	D_x = 1.443 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 1937 reflections
a = 7.7522 (11) Å	θ = 5.3–44.2°
b = 15.413 (2) Å	µ = 0.13 mm⁻¹
c = 12.2848 (17) Å	T = 293 K
β = 106.194 (2)°	Prismatic, green
V = 1409.6 (3) Å³	0.40 × 0.37 × 0.23 mm
Z = 4

Data collection top

Bruker SMART CCD area-detector diffractometer	2622 independent reflections
Radiation source: fine-focus sealed tube	1612 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.111
ϕ and ω scans	θ_max = 25.5°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2002)	h = −9→8
T_min = 0.640, T_max = 1.000	k = −10→18
7288 measured reflections	l = −13→14

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.063	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.174	H-atom parameters constrained
S = 0.94	w = 1/[σ²(F_o²) + (0.0971P)²] where P = (F_o² + 2F_c²)/3
2622 reflections	(Δ/σ)_max < 0.001
199 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.24 e Å⁻³

Crystal data top

C₁₇H₁₀F₄O	V = 1409.6 (3) Å³
M_r = 306.25	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 7.7522 (11) Å	µ = 0.13 mm⁻¹
b = 15.413 (2) Å	T = 293 K
c = 12.2848 (17) Å	0.40 × 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)
T_min = 0.640, T_max = 1.000	R_int = 0.111
7288 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.063	0 restraints
wR(F²) = 0.174	H-atom parameters constrained
S = 0.94	Δρ_max = 0.27 e Å⁻³
2622 reflections	Δρ_min = −0.24 e Å⁻³
199 parameters

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

	x	y	z	U_iso*/U_eq
F1	0.1321 (2)	−0.05696 (10)	−0.13761 (11)	0.0953 (6)
F2	0.2040 (3)	−0.14772 (13)	0.23505 (14)	0.1253 (7)
F3	0.4725 (3)	0.31282 (12)	−0.12340 (13)	0.1193 (7)
F4	0.7788 (3)	0.37861 (11)	0.25107 (15)	0.1277 (7)
O1	0.4636 (3)	0.11929 (12)	0.21918 (15)	0.0902 (6)
C1	0.4216 (3)	0.12103 (15)	0.1155 (2)	0.0650 (6)
C2	0.3222 (3)	0.04845 (15)	0.0490 (2)	0.0651 (6)
H2	0.2925	0.0506	−0.0297	0.078*
C3	0.2739 (3)	−0.01982 (16)	0.09889 (19)	0.0665 (6)
H3	0.3101	−0.0180	0.1777	0.080*
C4	0.1752 (3)	−0.09625 (15)	0.05189 (18)	0.0625 (6)
C5	0.1051 (3)	−0.11493 (15)	−0.06245 (19)	0.0654 (6)
C6	0.0106 (3)	−0.18811 (17)	−0.1029 (2)	0.0761 (7)
H6	−0.0336	−0.1970	−0.1806	0.091*
C7	−0.0187 (4)	−0.24790 (18)	−0.0290 (3)	0.0816 (8)
H7	−0.0837	−0.2979	−0.0561	0.098*
C8	0.0473 (4)	−0.23481 (19)	0.0854 (3)	0.0908 (8)
H8	0.0285	−0.2755	0.1368	0.109*
C9	0.1404 (4)	−0.16122 (19)	0.1214 (2)	0.0793 (7)
C10	0.4659 (3)	0.19589 (16)	0.0545 (2)	0.0672 (6)
H10	0.4252	0.1973	−0.0242	0.081*
C11	0.5625 (3)	0.26144 (16)	0.10904 (19)	0.0657 (6)
H11	0.5979	0.2561	0.1876	0.079*
C12	0.6217 (3)	0.33956 (16)	0.06650 (19)	0.0652 (6)
C13	0.5821 (3)	0.36416 (17)	−0.0465 (2)	0.0776 (7)
C14	0.6445 (4)	0.4382 (2)	−0.0837 (3)	0.0964 (9)
H14	0.6124	0.4518	−0.1605	0.116*
C15	0.7535 (4)	0.4915 (2)	−0.0071 (3)	0.0980 (9)
H15	0.7977	0.5417	−0.0316	0.118*
C16	0.7993 (4)	0.4721 (2)	0.1059 (3)	0.1009 (9)
H16	0.8741	0.5086	0.1588	0.121*
C17	0.7330 (3)	0.39840 (19)	0.1388 (2)	0.0832 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.1352 (13)	0.0939 (11)	0.0506 (8)	−0.0214 (9)	0.0155 (8)	0.0034 (7)
F2	0.1765 (17)	0.1274 (15)	0.0600 (10)	−0.0324 (12)	0.0129 (10)	0.0212 (9)
F3	0.1636 (15)	0.1215 (14)	0.0553 (9)	−0.0532 (12)	0.0018 (10)	0.0006 (9)
F4	0.1733 (17)	0.1124 (14)	0.0678 (11)	−0.0292 (12)	−0.0153 (10)	−0.0118 (10)
O1	0.1242 (15)	0.0820 (13)	0.0543 (11)	−0.0036 (10)	0.0084 (10)	−0.0012 (8)
C1	0.0676 (14)	0.0680 (15)	0.0553 (14)	0.0125 (11)	0.0102 (11)	−0.0008 (11)
C2	0.0719 (14)	0.0696 (15)	0.0512 (13)	0.0085 (11)	0.0131 (11)	−0.0007 (11)
C3	0.0693 (14)	0.0775 (17)	0.0506 (13)	0.0115 (12)	0.0134 (11)	0.0023 (12)
C4	0.0636 (13)	0.0656 (14)	0.0564 (14)	0.0099 (11)	0.0138 (10)	0.0024 (11)
C5	0.0739 (14)	0.0653 (15)	0.0564 (14)	0.0119 (12)	0.0175 (11)	0.0070 (11)
C6	0.0829 (16)	0.0755 (17)	0.0668 (16)	0.0058 (14)	0.0154 (13)	−0.0075 (13)
C7	0.0841 (17)	0.0689 (17)	0.093 (2)	0.0029 (13)	0.0272 (16)	−0.0040 (15)
C8	0.107 (2)	0.0768 (19)	0.093 (2)	0.0019 (16)	0.0336 (18)	0.0170 (16)
C9	0.0933 (18)	0.0828 (19)	0.0561 (15)	0.0050 (15)	0.0114 (13)	0.0086 (13)
C10	0.0671 (14)	0.0771 (17)	0.0525 (13)	0.0059 (12)	0.0088 (11)	−0.0050 (12)
C11	0.0675 (13)	0.0731 (16)	0.0518 (13)	0.0063 (12)	0.0087 (11)	−0.0052 (11)
C12	0.0629 (13)	0.0707 (16)	0.0588 (14)	0.0052 (11)	0.0118 (11)	−0.0061 (11)
C13	0.0811 (16)	0.0853 (18)	0.0611 (15)	−0.0131 (14)	0.0109 (12)	−0.0040 (13)
C14	0.111 (2)	0.096 (2)	0.0788 (19)	−0.0156 (18)	0.0214 (17)	0.0115 (16)
C15	0.099 (2)	0.082 (2)	0.112 (3)	−0.0120 (16)	0.0258 (19)	0.0076 (18)
C16	0.094 (2)	0.081 (2)	0.112 (3)	−0.0177 (17)	0.0032 (18)	−0.0135 (18)
C17	0.0870 (17)	0.0844 (19)	0.0655 (17)	−0.0005 (15)	0.0004 (13)	−0.0089 (14)

Geometric parameters (Å, º) top

F1—C5	1.342 (3)	C7—H7	0.9300
F2—C9	1.361 (3)	C8—C9	1.351 (4)
F3—C13	1.339 (3)	C8—H8	0.9300
F4—C17	1.360 (3)	C10—C11	1.323 (3)
O1—C1	1.224 (3)	C10—H10	0.9300
C1—C10	1.468 (3)	C11—C12	1.438 (3)
C1—C2	1.470 (3)	C11—H11	0.9300
C2—C3	1.323 (3)	C12—C13	1.388 (3)
C2—H2	0.9300	C12—C17	1.389 (3)
C3—C4	1.436 (3)	C13—C14	1.367 (4)
C3—H3	0.9300	C14—C15	1.353 (4)
C4—C5	1.388 (3)	C14—H14	0.9300
C4—C9	1.390 (4)	C15—C16	1.367 (4)
C5—C6	1.361 (3)	C15—H15	0.9300
C6—C7	1.357 (4)	C16—C17	1.354 (4)
C6—H6	0.9300	C16—H16	0.9300
C7—C8	1.370 (4)

O1—C1—C10	121.1 (2)	F2—C9—C4	116.3 (2)
O1—C1—C2	120.5 (2)	C11—C10—C1	121.5 (2)
C10—C1—C2	118.4 (2)	C11—C10—H10	119.3
C3—C2—C1	121.3 (2)	C1—C10—H10	119.3
C3—C2—H2	119.3	C10—C11—C12	130.4 (2)
C1—C2—H2	119.3	C10—C11—H11	114.8
C2—C3—C4	130.9 (2)	C12—C11—H11	114.8
C2—C3—H3	114.6	C13—C12—C17	112.7 (2)
C4—C3—H3	114.6	C13—C12—C11	126.0 (2)
C5—C4—C9	112.6 (2)	C17—C12—C11	121.2 (2)
C5—C4—C3	126.3 (2)	F3—C13—C14	118.1 (2)
C9—C4—C3	121.1 (2)	F3—C13—C12	117.6 (2)
F1—C5—C6	118.1 (2)	C14—C13—C12	124.2 (3)
F1—C5—C4	117.8 (2)	C15—C14—C13	119.0 (3)
C6—C5—C4	124.1 (2)	C15—C14—H14	120.5
C7—C6—C5	119.4 (3)	C13—C14—H14	120.5
C7—C6—H6	120.3	C14—C15—C16	120.6 (3)
C5—C6—H6	120.3	C14—C15—H15	119.7
C6—C7—C8	120.2 (3)	C16—C15—H15	119.7
C6—C7—H7	119.9	C17—C16—C15	118.3 (3)
C8—C7—H7	119.9	C17—C16—H16	120.9
C9—C8—C7	118.2 (3)	C15—C16—H16	120.9
C9—C8—H8	120.9	C16—C17—F4	118.5 (3)
C7—C8—H8	120.9	C16—C17—C12	125.2 (3)
C8—C9—F2	118.1 (2)	F4—C17—C12	116.2 (3)
C8—C9—C4	125.5 (3)

O1—C1—C2—C3	0.7 (3)	O1—C1—C10—C11	4.4 (3)
C10—C1—C2—C3	−178.2 (2)	C2—C1—C10—C11	−176.71 (19)
C1—C2—C3—C4	178.8 (2)	C1—C10—C11—C12	179.4 (2)
C2—C3—C4—C5	−0.4 (4)	C10—C11—C12—C13	2.2 (4)
C2—C3—C4—C9	179.5 (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—F1	0.5 (3)	C11—C12—C13—F3	3.1 (4)
C9—C4—C5—C6	0.8 (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—C7	179.9 (2)	F3—C13—C14—C15	179.2 (3)
C4—C5—C6—C7	−0.2 (4)	C12—C13—C14—C15	0.8 (5)
C5—C6—C7—C8	−0.3 (4)	C13—C14—C15—C16	−0.7 (5)
C6—C7—C8—C9	0.3 (4)	C14—C15—C16—C17	0.1 (5)
C7—C8—C9—F2	179.2 (2)	C15—C16—C17—F4	179.7 (3)
C7—C8—C9—C4	0.4 (4)	C15—C16—C17—C12	0.5 (5)
C5—C4—C9—C8	−0.9 (4)	C13—C12—C17—C16	−0.4 (4)
C3—C4—C9—C8	179.2 (2)	C11—C12—C17—C16	177.9 (3)
C5—C4—C9—F2	−179.7 (2)	C13—C12—C17—F4	−179.6 (2)
C3—C4—C9—F2	0.4 (3)	C11—C12—C17—F4	−1.3 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C16—H16···O1ⁱ	0.93	2.38	3.307 (4)	171
C8—H8···O1ⁱⁱ	0.93	2.39	3.308 (3)	170

Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+1/2, y−1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₇H₁₀F₄O
M_r	306.25
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	7.7522 (11), 15.413 (2), 12.2848 (17)
β (°)	106.194 (2)
V (Å³)	1409.6 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.40 × 0.37 × 0.23

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2002)
T_min, T_max	0.640, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	7288, 2622, 1612
R_int	0.111
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.063, 0.174, 0.94
No. of reflections	2622
No. of parameters	199
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.24

Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009), SHELXTL (Sheldrick, 2008).