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

Jun-Da Huang; Qin-Qin Tang; Xiao-Yan Chen; Yun Ye; Yi Wang

doi:10.1107/S1600536811007070

. 2011 Mar 2;67(Pt 4):o758. doi: 10.1107/S1600536811007070

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

Jun-Da Huang ^a, Qin-Qin Tang ^a, Xiao-Yan Chen ^b, Yun Ye ^a, Yi Wang ^a,^*

PMCID: PMC3099841 PMID: 21754055

Abstract

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.

Related literature

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

Crystal data

C₁₇H₁₀F₄O
M _r = 306.25
Monoclinic,
a = 7.7522 (11) Å
b = 15.413 (2) Å
c = 12.2848 (17) Å
β = 106.194 (2)°
V = 1409.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 293 K
0.40 × 0.37 × 0.23 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2002 ▶) T _min = 0.640, T _max = 1.000
7288 measured reflections
2622 independent reflections
1612 reflections with I > 2σ(I)
R _int = 0.111

Refinement

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

Data collection: SMART (Bruker, 2002 ▶); cell refinement: SAINT (Bruker, 2002 ▶); data reduction: SAINT; 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.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811007070/dn2659sup1.cif

e-67-0o758-sup1.cif^{(17.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811007070/dn2659Isup2.hkl

e-67-0o758-Isup2.hkl^{(128.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

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

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

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.

supplementary crystallographic information

Comment

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).

Experimental

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.