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

Jiang, C.; Feng, Z.; Song, B.; Li, X.; Li, X.

doi:10.1107/S1600536810011499

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

C. Jiang, Z. Feng, B. Song, X. Li and X. Li

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.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536810011499/ng2751sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536810011499/ng2751Isup2.hkl Contains datablock I

CCDC reference: 777927

checkCIF report

Key indicators

Single-crystal X-ray study
T = 293 K
Mean (C-C) = 0.003 Å
R factor = 0.056
wR factor = 0.156
Data-to-parameter ratio = 15.1

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT230_ALERT_2_C Hirshfeld Test Diff for    C7     --  C8      ..       6.30 su
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          1
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          4
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600         22

Alert level G
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 = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   2 ALERT level G = General alerts; check

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

Comment top

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 (Liang et al., 2009; 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).

Related literature top

For background and related structures, see: Liang et al. (2007a,b, 2009); Zhao et al. (2009, 2010a,b).

Experimental top

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 CH₂Cl₂/CH₃OH mixture (5:2 v/v) by slow evaporation (mp 132-135.4 K).

Structure description top

For background and related structures, see: Liang et al. (2007a,b, 2009); Zhao et al. (2009, 2010a,b).

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); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of the title compound, showing 30% displacement ellipsoids for the non-hydrogen atoms. Hydrogen atoms are drawn as spheres of arbitrary radius.

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

Crystal data top

C₂₀H₁₄F₄O	F(000) = 712
M_r = 346.31	D_x = 1.450 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 15.824 (2) Å	Cell parameters from 1858 reflections
b = 6.3128 (8) Å	θ = 2.4–22.3°
c = 17.097 (2) Å	µ = 0.12 mm⁻¹
β = 111.756 (3)°	T = 293 K
V = 1586.2 (3) Å³	Prismatic, colorless
Z = 4	0.43 × 0.35 × 0.27 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	3425 independent reflections
Radiation source: fine-focus sealed tube	2018 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.049
phi and ω scans	θ_max = 27.0°, θ_min = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 2002)	h = −15→20
T_min = 0.490, T_max = 1.000	k = −7→8
8935 measured reflections	l = −21→18

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.056	H-atom parameters constrained
wR(F²) = 0.156	w = 1/[σ²(F_o²) + (0.082P)²] where P = (F_o² + 2F_c²)/3
S = 0.93	(Δ/σ)_max < 0.001
3425 reflections	Δρ_max = 0.23 e Å⁻³
227 parameters	Δρ_min = −0.24 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.015 (2)

Crystal data top

C₂₀H₁₄F₄O	V = 1586.2 (3) Å³
M_r = 346.31	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 15.824 (2) Å	µ = 0.12 mm⁻¹
b = 6.3128 (8) Å	T = 293 K
c = 17.097 (2) Å	0.43 × 0.35 × 0.27 mm
β = 111.756 (3)°

Data collection top

Bruker SMART CCD area-detector diffractometer	3425 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2002)	2018 reflections with I > 2σ(I)
T_min = 0.490, T_max = 1.000	R_int = 0.049
8935 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.056	0 restraints
wR(F²) = 0.156	H-atom parameters constrained
S = 0.93	Δρ_max = 0.23 e Å⁻³
3425 reflections	Δρ_min = −0.24 e Å⁻³
227 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	0.40753 (15)	0.4774 (3)	1.14644 (10)	0.1192 (7)
F2	0.42662 (12)	1.2350 (2)	1.00801 (10)	0.0934 (5)
F3	0.00929 (10)	0.5237 (2)	0.36811 (8)	0.0809 (5)
F4	0.16575 (11)	1.2677 (2)	0.49902 (9)	0.0839 (5)
O1	0.17234 (12)	1.1232 (3)	0.76698 (9)	0.0796 (6)
C1	0.20606 (14)	0.9520 (4)	0.76181 (12)	0.0520 (6)
C2	0.26784 (13)	0.8418 (3)	0.83949 (12)	0.0466 (5)
C3	0.29758 (14)	0.9609 (4)	0.90938 (13)	0.0556 (6)
H3	0.2766	1.0999	0.9033	0.067*
C4	0.35876 (14)	0.9001 (4)	0.99398 (12)	0.0528 (6)
C5	0.35519 (16)	0.7068 (4)	1.03101 (14)	0.0633 (6)
H5	0.3125	0.6053	1.0019	0.076*
C6	0.4149 (2)	0.6673 (5)	1.11059 (15)	0.0760 (8)
C7	0.47922 (18)	0.8090 (6)	1.15698 (15)	0.0836 (9)
H7	0.5196	0.7755	1.2108	0.100*
C8	0.48225 (18)	1.0026 (5)	1.12152 (16)	0.0794 (8)
H8	0.5247	1.1039	1.1512	0.095*
C9	0.42230 (17)	1.0439 (4)	1.04241 (14)	0.0654 (7)
C10	0.18662 (13)	0.8503 (3)	0.67808 (12)	0.0466 (5)
C11	0.14905 (14)	0.9764 (3)	0.61179 (13)	0.0517 (6)
H11	0.1403	1.1160	0.6244	0.062*
C12	0.11951 (13)	0.9273 (3)	0.52187 (12)	0.0470 (5)
C13	0.07950 (14)	0.7364 (3)	0.48623 (12)	0.0503 (5)
H13	0.0731	0.6275	0.5202	0.060*
C14	0.04988 (14)	0.7102 (4)	0.40128 (13)	0.0556 (6)
C15	0.05733 (15)	0.8634 (4)	0.34722 (14)	0.0614 (7)
H15	0.0367	0.8396	0.2895	0.074*
C16	0.09649 (17)	1.0538 (4)	0.38151 (14)	0.0629 (7)
H16	0.1025	1.1624	0.3472	0.076*
C17	0.12608 (15)	1.0796 (3)	0.46646 (14)	0.0562 (6)
C18	0.29633 (15)	0.6182 (3)	0.83255 (12)	0.0528 (6)
H18A	0.2525	0.5215	0.8405	0.063*
H18B	0.3549	0.5916	0.8769	0.063*
C19	0.30317 (15)	0.5754 (4)	0.74764 (12)	0.0541 (6)
H19A	0.3514	0.6616	0.7421	0.065*
H19B	0.3188	0.4279	0.7446	0.065*
C20	0.21500 (14)	0.6242 (3)	0.67610 (12)	0.0523 (6)
H20A	0.2220	0.5968	0.6230	0.063*
H20B	0.1677	0.5313	0.6796	0.063*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.193 (2)	0.0997 (14)	0.0587 (9)	0.0260 (13)	0.0392 (11)	0.0185 (9)
F2	0.1281 (14)	0.0767 (12)	0.0776 (10)	−0.0307 (10)	0.0406 (10)	−0.0231 (8)
F3	0.0950 (11)	0.0712 (10)	0.0577 (8)	−0.0144 (8)	0.0066 (7)	−0.0117 (7)
F4	0.1145 (12)	0.0498 (9)	0.0738 (9)	−0.0116 (8)	0.0189 (9)	0.0087 (7)
O1	0.1081 (14)	0.0625 (12)	0.0539 (10)	0.0340 (10)	0.0133 (9)	−0.0087 (8)
C1	0.0591 (13)	0.0470 (14)	0.0464 (12)	0.0073 (11)	0.0155 (10)	−0.0066 (10)
C2	0.0484 (12)	0.0478 (13)	0.0427 (11)	−0.0004 (9)	0.0159 (9)	−0.0013 (9)
C3	0.0606 (14)	0.0549 (14)	0.0478 (12)	0.0038 (11)	0.0159 (11)	−0.0042 (10)
C4	0.0539 (12)	0.0624 (15)	0.0421 (11)	0.0039 (11)	0.0179 (10)	−0.0090 (10)
C5	0.0741 (16)	0.0689 (17)	0.0456 (12)	−0.0015 (13)	0.0206 (12)	−0.0073 (11)
C6	0.104 (2)	0.082 (2)	0.0416 (13)	0.0253 (16)	0.0262 (14)	0.0058 (13)
C7	0.0701 (17)	0.126 (3)	0.0422 (14)	0.0292 (18)	0.0062 (13)	−0.0182 (16)
C8	0.0680 (17)	0.109 (2)	0.0561 (16)	−0.0100 (16)	0.0176 (14)	−0.0303 (16)
C9	0.0707 (16)	0.0769 (19)	0.0497 (14)	−0.0028 (14)	0.0235 (13)	−0.0184 (13)
C10	0.0472 (11)	0.0444 (13)	0.0433 (11)	0.0023 (9)	0.0113 (9)	−0.0041 (9)
C11	0.0588 (13)	0.0431 (13)	0.0483 (12)	0.0081 (10)	0.0143 (10)	−0.0010 (9)
C12	0.0463 (11)	0.0458 (13)	0.0454 (11)	0.0090 (9)	0.0128 (9)	0.0046 (9)
C13	0.0536 (12)	0.0474 (13)	0.0445 (12)	0.0013 (10)	0.0118 (10)	0.0054 (9)
C14	0.0550 (13)	0.0537 (15)	0.0494 (13)	0.0027 (11)	0.0092 (10)	−0.0019 (11)
C15	0.0648 (15)	0.0728 (18)	0.0429 (12)	0.0142 (13)	0.0157 (11)	0.0048 (12)
C16	0.0729 (15)	0.0599 (16)	0.0547 (14)	0.0092 (13)	0.0221 (12)	0.0188 (12)
C17	0.0619 (14)	0.0417 (14)	0.0577 (14)	0.0045 (11)	0.0137 (11)	0.0063 (11)
C18	0.0606 (13)	0.0513 (14)	0.0437 (11)	0.0047 (11)	0.0161 (10)	0.0013 (10)
C19	0.0617 (13)	0.0494 (14)	0.0476 (12)	0.0110 (11)	0.0159 (10)	−0.0016 (10)
C20	0.0626 (13)	0.0462 (14)	0.0432 (11)	0.0059 (10)	0.0140 (10)	−0.0039 (9)

Geometric parameters (Å, º) top

F1—C6	1.371 (3)	C10—C20	1.500 (3)
F2—C9	1.355 (3)	C11—C12	1.465 (3)
F3—C14	1.360 (2)	C11—H11	0.9300
F4—C17	1.362 (2)	C12—C17	1.381 (3)
O1—C1	1.223 (2)	C12—C13	1.392 (3)
C1—C10	1.493 (3)	C13—C14	1.361 (3)
C1—C2	1.497 (3)	C13—H13	0.9300
C2—C3	1.341 (3)	C14—C15	1.372 (3)
C2—C18	1.500 (3)	C15—C16	1.380 (3)
C3—C4	1.462 (3)	C15—H15	0.9300
C3—H3	0.9300	C16—C17	1.361 (3)
C4—C9	1.380 (3)	C16—H16	0.9300
C4—C5	1.386 (3)	C18—C19	1.519 (3)
C5—C6	1.361 (3)	C18—H18A	0.9700
C5—H5	0.9300	C18—H18B	0.9700
C6—C7	1.366 (4)	C19—C20	1.508 (3)
C7—C8	1.373 (4)	C19—H19A	0.9700
C7—H7	0.9300	C19—H19B	0.9700
C8—C9	1.359 (3)	C20—H20A	0.9700
C8—H8	0.9300	C20—H20B	0.9700
C10—C11	1.331 (3)

O1—C1—C10	120.60 (18)	C13—C12—C11	124.00 (19)
O1—C1—C2	120.36 (18)	C14—C13—C12	119.5 (2)
C10—C1—C2	119.03 (19)	C14—C13—H13	120.2
C3—C2—C1	115.35 (19)	C12—C13—H13	120.2
C3—C2—C18	125.57 (18)	F3—C14—C13	118.2 (2)
C1—C2—C18	118.93 (17)	F3—C14—C15	118.3 (2)
C2—C3—C4	128.3 (2)	C13—C14—C15	123.5 (2)
C2—C3—H3	115.9	C14—C15—C16	117.7 (2)
C4—C3—H3	115.9	C14—C15—H15	121.2
C9—C4—C5	116.7 (2)	C16—C15—H15	121.2
C9—C4—C3	119.3 (2)	C17—C16—C15	118.7 (2)
C5—C4—C3	124.0 (2)	C17—C16—H16	120.6
C6—C5—C4	119.1 (2)	C15—C16—H16	120.6
C6—C5—H5	120.4	C16—C17—F4	117.7 (2)
C4—C5—H5	120.4	C16—C17—C12	124.4 (2)
C5—C6—C7	123.5 (3)	F4—C17—C12	117.9 (2)
C5—C6—F1	117.7 (3)	C2—C18—C19	111.88 (17)
C7—C6—F1	118.8 (2)	C2—C18—H18A	109.2
C6—C7—C8	117.8 (2)	C19—C18—H18A	109.2
C6—C7—H7	121.1	C2—C18—H18B	109.2
C8—C7—H7	121.1	C19—C18—H18B	109.2
C9—C8—C7	119.0 (3)	H18A—C18—H18B	107.9
C9—C8—H8	120.5	C20—C19—C18	111.50 (18)
C7—C8—H8	120.5	C20—C19—H19A	109.3
F2—C9—C8	118.3 (2)	C18—C19—H19A	109.3
F2—C9—C4	117.9 (2)	C20—C19—H19B	109.3
C8—C9—C4	123.8 (3)	C18—C19—H19B	109.3
C11—C10—C1	115.29 (19)	H19A—C19—H19B	108.0
C11—C10—C20	126.35 (18)	C10—C20—C19	111.77 (17)
C1—C10—C20	118.28 (17)	C10—C20—H20A	109.3
C10—C11—C12	129.4 (2)	C19—C20—H20A	109.3
C10—C11—H11	115.3	C10—C20—H20B	109.3
C12—C11—H11	115.3	C19—C20—H20B	109.3
C17—C12—C13	116.12 (19)	H20A—C20—H20B	107.9
C17—C12—C11	119.8 (2)

O1—C1—C2—C3	−13.6 (3)	C2—C1—C10—C20	11.5 (3)
C10—C1—C2—C3	166.2 (2)	C1—C10—C11—C12	−178.3 (2)
O1—C1—C2—C18	170.6 (2)	C20—C10—C11—C12	5.2 (4)
C10—C1—C2—C18	−9.7 (3)	C10—C11—C12—C17	−146.9 (2)
C1—C2—C3—C4	−179.3 (2)	C10—C11—C12—C13	36.8 (4)
C18—C2—C3—C4	−3.8 (4)	C17—C12—C13—C14	0.1 (3)
C2—C3—C4—C9	141.8 (2)	C11—C12—C13—C14	176.5 (2)
C2—C3—C4—C5	−40.8 (4)	C12—C13—C14—F3	−178.60 (18)
C9—C4—C5—C6	−1.8 (3)	C12—C13—C14—C15	0.2 (3)
C3—C4—C5—C6	−179.3 (2)	F3—C14—C15—C16	178.34 (19)
C4—C5—C6—C7	0.1 (4)	C13—C14—C15—C16	−0.5 (4)
C4—C5—C6—F1	177.8 (2)	C14—C15—C16—C17	0.5 (4)
C5—C6—C7—C8	1.1 (4)	C15—C16—C17—F4	179.0 (2)
F1—C6—C7—C8	−176.6 (2)	C15—C16—C17—C12	−0.2 (4)
C6—C7—C8—C9	−0.5 (4)	C13—C12—C17—C16	0.0 (3)
C7—C8—C9—F2	−179.5 (2)	C11—C12—C17—C16	−176.6 (2)
C7—C8—C9—C4	−1.4 (4)	C13—C12—C17—F4	−179.30 (18)
C5—C4—C9—F2	−179.4 (2)	C11—C12—C17—F4	4.1 (3)
C3—C4—C9—F2	−1.7 (3)	C3—C2—C18—C19	−143.7 (2)
C5—C4—C9—C8	2.5 (4)	C1—C2—C18—C19	31.7 (3)
C3—C4—C9—C8	−179.8 (2)	C2—C18—C19—C20	−56.2 (3)
O1—C1—C10—C11	14.5 (3)	C11—C10—C20—C19	140.9 (2)
C2—C1—C10—C11	−165.28 (19)	C1—C10—C20—C19	−35.6 (3)
O1—C1—C10—C20	−168.7 (2)	C18—C19—C20—C10	58.3 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C16—H16···O1ⁱ	0.93	2.46	3.343 (3)	158

Symmetry code: (i) x, −y+5/2, z−1/2.

Experimental details

Crystal data
Chemical formula	C₂₀H₁₄F₄O
M_r	346.31
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	15.824 (2), 6.3128 (8), 17.097 (2)
β (°)	111.756 (3)
V (Å³)	1586.2 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.43 × 0.35 × 0.27

Data collection
Diffractometer	Bruker SMART CCD area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2002)
T_min, T_max	0.490, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	8935, 3425, 2018
R_int	0.049
(sin θ/λ)_max (Å⁻¹)	0.639

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.056, 0.156, 0.93
No. of reflections	3425
No. of parameters	227
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.24

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

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		EndNote
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Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Text
		Plain Text

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

Supporting information

Key indicators

checkCIF/PLATON results

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