(2E,6E)-2,6-Bis[(5-methyl­thio­phen-2-yl)­methyl­ene]cyclo­hexa­none

In the title mol­ecule, C₁₈H₁₈OS₂, the geometric parameters are normal and the two S atoms are both in an anti arrangement with respect to the carbonyl O atom. The dihedral angle between the thio­phene rings is 5.16 (9)°.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.056
• wR factor = 0.144
• Data-to-parameter ratio = 17.8

checkCIF/PLATON results

No syntax errors found



Alert level C
ABSTM02_ALERT_3_C  The ratio of expected to reported Tmax/Tmin(RR') is < 0.90
            Tmin and Tmax reported:      0.693     1.000
            Tmin(prime) and Tmax expected:      0.845     0.951
            RR(prime) =      0.780
            Please check that your absorption correction is appropriate.
RINTA01_ALERT_3_C  The value of Rint is greater than 0.10
            Rint given   0.118
PLAT020_ALERT_3_C The value of Rint is greater than 0.10 .........       0.12
PLAT061_ALERT_3_C Tmax/Tmin Range Test RR' too Large .............       0.78
PLAT062_ALERT_4_C Rescale T(min) & T(max) by .....................       0.95
PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent .....          ?

Alert level G
ABSTM02_ALERT_3_G  When printed, the submitted absorption T values will be
            replaced by the scaled T values. Since the ratio of scaled T's
            is identical to the ratio of reported T values, the scaling
            does not imply a change to the absorption corrections used in
            the study.
            Ratio of Tmax expected/reported      0.951
            Tmax scaled      0.951 Tmin scaled      0.659
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
   6 ALERT level C = Check and explain
   3 ALERT level G = General alerts; check

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   5 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

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S1. Comment

Curcumin, a natural and multifunctional extract from ginger genus plants, is an excellent lead compound for new antiinflammatory and antitumor drug design. It has been reported to possess a variety of bioactivities such as antitumor, antioxidation, antiinflammation, and antivirus as a inhibitor of HIV integrase (Jagetia & Aggarwal, 2007; Kuttan et al., 2007). Many studies on the structural design and modification of curcumin have been carried out (Weber et al., 2005; Ryu et al., 2006). Our group has designed and synthesized a series of curcumin analogues without the central beta-ketone moiety, which is considered to be cleaved by the noncytochrome P450 pathway in the liver and plays an important role in the poor pharmacokinetics and bioavalability of curcumin (Deng et al., 2007). Some crystal structures of monocarbonyl analogues of curcumin have reported e.g. (2E,5E)-2,5-bis(2-bromobenzylidene)cyclopentanone (Liang et al., 2007), 2,5-bis(3,4-dimethoxybenzylidene)cyclopentanone (Butcher, Jasinski, Narayana et al., 2007), and 1,5-Bis(4-fluorophenyl)penta-1,4-dien-3-one (Butcher, Jasinski, Sarojini et al., 2007). In this paper, we present the crystal structure of the title heterocyclic analogue of curcumin, (2E,6E)-2,6-bis((5-methylthiophen-2-yl)methylene) cyclohexanone. The geometrical parameters of the title molecule (Fig. 1) are normal, the two sulfur atoms are in an anti arrangment with respect the carbonyl O atom and the dihedral angle between the five-membered thiophene ring planes is 5.16 (9)°.

Related literature

For related structures, see: Butcher, Jasinski, Narayana et al.(2007); Butcher, Jasinski, Sarojini et al. (2007). For background information, see: Liang et al. (2007); Jagetia & Aggarwal (2007); Kuttan et al. (2007); Deng et al. (2007); Ryu et al. (2006); Weber et al. (2005).

S2. Experimental

To a solution of 15 mmol 5-methylthiophene-2-carbaldehyde in MeOH (10 ml) was added 7.5 mmol cyclopentanone. The solution was stirred at room temperature for 15 min, followed by added dropwise 2.0 mol/L NaOCH3 (3.75 ml, 7.5 mmol). The mixture was stirred at R·T. for 2 h and monitored with TLC. When the reaction was complete, the residue was poured into saturated NH₄Cl solution and filtered. The precipitate was washed and purified by chromatography over silica gel using CH₂Cl₂ / CH₃OH as the eluent to afford the pure product (yield: 71.8%). Single crystals were grown in a CH₂Cl₂—CH₃CH₂OH mixture (4:1 v/v) by slow evaporation (mp 438–440 K). 1H-NMR (CDCl₃): 1.93 (2H, m, CH2), 2.54 (6H, s, CH3), 2.88 (4H, t, J=4.8 Hz, CH2—CH2), 6.80 (2H, d, J = 3.6 Hz, Ar—H3), 7.18 (2H, d, J = 3.6 Hz, Ar—H4), 7.89 (2H, s, CH=C). ESI-MS m/z: 315.37 (M+1)+, calcd for C₁₈H₁₈O_S2: 314.46.

S3. Refinement

The H atoms were positioned geometrically (C—H = 0.93–0.97 Å) with U_iso(H) = 1.2U_eq(C) or 1.5U_eq(C) for methyl H atoms.

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SAINT (Siemens, 1994); data reduction: SAINT (Siemens, 1994); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 1999); software used to prepare material for publication: SHELXTL (Sheldrick, 1999).

Figures

Fig. 1. The molecular structure of with atom numbering, shoiwng xx% displacement ellipsoids for the non-hydrogen atoms.

(2E,6E)-2,6-Bis[(5-methylthiophen-2-yl)methylene]cyclohexanone

Crystal data

C18H18OS2	F(000) = 664
Mr = 314.44	Dx = 1.328 Mg m^−3
Monoclinic, P21/n	Melting point: 438-440K K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 15.0631 (19) Å	Cell parameters from 2150 reflections
b = 5.9790 (8) Å	θ = 4.7–52.9°
c = 17.689 (2) Å	µ = 0.33 mm^−1
β = 99.204 (2)°	T = 293 K
V = 1572.6 (4) Å^3	Prismatic, yellow
Z = 4	0.50 × 0.33 × 0.15 mm

Data collection

Bruker SMART CCD area-detector diffractometer	3419 independent reflections
Radiation source: fine-focus sealed tube	2425 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.118
φ and ω scans	θmax = 27.0°, θmin = 1.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −19→13
Tmin = 0.693, Tmax = 1.000	k = −7→7
8803 measured reflections	l = −22→22

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.056	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.144	H-atom parameters constrained
S = 0.96	w = 1/[σ^2(Fo^2) + (0.0606P)^2] where P = (Fo^2 + 2Fc^2)/3
3419 reflections	(Δ/σ)max = 0.001
192 parameters	Δρmax = 0.48 e Å^−3
0 restraints	Δρmin = −0.30 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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 (Ų)

	x	y	z	Uiso*/Ueq
S1	0.66053 (5)	0.60400 (10)	1.02262 (4)	0.0457 (2)
S2	0.42563 (4)	0.72792 (11)	0.53701 (4)	0.0500 (2)
O1	0.46099 (14)	0.1525 (3)	0.78293 (11)	0.0650 (6)
C1	0.49669 (17)	0.3352 (4)	0.78007 (14)	0.0441 (6)
C2	0.48304 (16)	0.4675 (4)	0.70766 (13)	0.0428 (6)
C3	0.53608 (18)	0.6800 (5)	0.70181 (15)	0.0529 (7)
H3A	0.4977	0.8077	0.7067	0.063*
H3B	0.5541	0.6869	0.6516	0.063*
C4	0.61929 (19)	0.6951 (5)	0.76260 (15)	0.0599 (8)
H4A	0.6625	0.5827	0.7528	0.072*
H4B	0.6469	0.8409	0.7603	0.072*
C5	0.59505 (19)	0.6594 (5)	0.84138 (14)	0.0540 (7)
H5A	0.6488	0.6735	0.8794	0.065*
H5B	0.5530	0.7743	0.8514	0.065*
C6	0.55374 (16)	0.4335 (4)	0.84869 (13)	0.0416 (6)
C7	0.56103 (16)	0.3136 (4)	0.91373 (14)	0.0417 (6)
H7	0.5328	0.1750	0.9078	0.050*
C8	0.60433 (16)	0.3593 (4)	0.99076 (14)	0.0405 (6)
C9	0.60517 (18)	0.2174 (4)	1.05115 (15)	0.0485 (6)
H9	0.5785	0.0767	1.0465	0.058*
C10	0.64957 (18)	0.3018 (5)	1.12083 (15)	0.0523 (7)
H10	0.6549	0.2228	1.1666	0.063*
C11	0.68413 (17)	0.5092 (5)	1.11535 (14)	0.0475 (6)
C12	0.7374 (2)	0.6518 (5)	1.17666 (16)	0.0664 (8)
H12A	0.7129	0.6373	1.2233	0.100*
H12B	0.7343	0.8054	1.1606	0.100*
H12C	0.7990	0.6038	1.1852	0.100*
C13	0.42223 (17)	0.3906 (4)	0.64973 (14)	0.0449 (6)
H13	0.3942	0.2582	0.6604	0.054*
C14	0.39269 (16)	0.4772 (4)	0.57379 (13)	0.0431 (6)
C15	0.33238 (17)	0.3723 (4)	0.51864 (15)	0.0491 (6)
H15	0.3056	0.2361	0.5266	0.059*
C16	0.31508 (17)	0.4888 (5)	0.44959 (15)	0.0515 (6)
H16	0.2764	0.4359	0.4071	0.062*
C17	0.35950 (16)	0.6853 (4)	0.44977 (14)	0.0457 (6)
C18	0.3575 (2)	0.8562 (5)	0.38763 (16)	0.0616 (8)
H18A	0.3248	0.7977	0.3407	0.092*
H18B	0.4179	0.8909	0.3807	0.092*
H18C	0.3285	0.9894	0.4016	0.092*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0494 (4)	0.0454 (4)	0.0407 (4)	−0.0035 (3)	0.0025 (3)	0.0017 (3)
S2	0.0466 (4)	0.0566 (4)	0.0437 (4)	−0.0097 (3)	−0.0021 (3)	0.0006 (3)
O1	0.0870 (16)	0.0497 (11)	0.0512 (12)	−0.0167 (10)	−0.0104 (10)	0.0022 (9)
C1	0.0469 (15)	0.0414 (14)	0.0422 (14)	−0.0026 (11)	0.0012 (11)	−0.0019 (10)
C2	0.0405 (14)	0.0490 (14)	0.0383 (13)	−0.0016 (11)	0.0043 (10)	−0.0025 (11)
C3	0.0497 (16)	0.0669 (17)	0.0391 (14)	−0.0130 (13)	−0.0023 (11)	0.0048 (12)
C4	0.0556 (18)	0.0796 (19)	0.0416 (16)	−0.0251 (15)	−0.0016 (12)	0.0056 (13)
C5	0.0581 (18)	0.0630 (17)	0.0378 (14)	−0.0171 (13)	−0.0015 (12)	0.0037 (12)
C6	0.0391 (14)	0.0456 (14)	0.0396 (13)	−0.0003 (11)	0.0044 (10)	−0.0006 (10)
C7	0.0390 (14)	0.0408 (13)	0.0446 (14)	−0.0001 (10)	0.0047 (11)	0.0004 (10)
C8	0.0342 (13)	0.0420 (14)	0.0445 (14)	0.0010 (10)	0.0034 (10)	0.0030 (10)
C9	0.0440 (15)	0.0463 (15)	0.0533 (16)	−0.0019 (11)	0.0020 (12)	0.0093 (11)
C10	0.0539 (17)	0.0612 (17)	0.0401 (15)	0.0029 (13)	0.0018 (12)	0.0123 (12)
C11	0.0440 (15)	0.0577 (16)	0.0393 (14)	0.0059 (12)	0.0015 (11)	0.0004 (11)
C12	0.071 (2)	0.080 (2)	0.0450 (17)	−0.0059 (17)	−0.0024 (14)	−0.0083 (14)
C13	0.0434 (14)	0.0484 (15)	0.0425 (14)	−0.0041 (11)	0.0052 (11)	−0.0023 (11)
C14	0.0372 (13)	0.0494 (14)	0.0424 (14)	−0.0036 (11)	0.0050 (10)	−0.0046 (11)
C15	0.0403 (15)	0.0564 (16)	0.0490 (15)	−0.0085 (12)	0.0028 (11)	−0.0031 (12)
C16	0.0414 (15)	0.0676 (17)	0.0421 (15)	−0.0013 (13)	−0.0038 (11)	−0.0093 (12)
C17	0.0363 (14)	0.0595 (16)	0.0398 (14)	−0.0005 (12)	0.0018 (10)	−0.0023 (11)
C18	0.0581 (19)	0.073 (2)	0.0516 (17)	0.0001 (15)	0.0025 (14)	0.0088 (14)

Geometric parameters (Å, º)

S1—C11	1.718 (2)	C8—C9	1.363 (3)
S1—C8	1.738 (2)	C9—C10	1.399 (4)
S2—C17	1.717 (2)	C9—H9	0.9300
S2—C14	1.738 (2)	C10—C11	1.355 (4)
O1—C1	1.222 (3)	C10—H10	0.9300
C1—C6	1.491 (3)	C11—C12	1.506 (4)
C1—C2	1.491 (3)	C12—H12A	0.9600
C2—C13	1.342 (3)	C12—H12B	0.9600
C2—C3	1.513 (3)	C12—H12C	0.9600
C3—C4	1.518 (3)	C13—C14	1.442 (3)
C3—H3A	0.9700	C13—H13	0.9300
C3—H3B	0.9700	C14—C15	1.374 (3)
C4—C5	1.511 (4)	C15—C16	1.394 (4)
C4—H4A	0.9700	C15—H15	0.9300
C4—H4B	0.9700	C16—C17	1.352 (4)
C5—C6	1.501 (3)	C16—H16	0.9300
C5—H5A	0.9700	C17—C18	1.497 (4)
C5—H5B	0.9700	C18—H18A	0.9600
C6—C7	1.345 (3)	C18—H18B	0.9600
C7—C8	1.440 (3)	C18—H18C	0.9600
C7—H7	0.9300
C11—S1—C8	92.72 (12)	C8—C9—H9	122.9
C17—S2—C14	92.81 (12)	C10—C9—H9	122.9
O1—C1—C6	121.2 (2)	C11—C10—C9	113.7 (2)
O1—C1—C2	120.6 (2)	C11—C10—H10	123.1
C6—C1—C2	118.2 (2)	C9—C10—H10	123.1
C13—C2—C1	117.2 (2)	C10—C11—C12	129.3 (2)
C13—C2—C3	122.6 (2)	C10—C11—S1	110.32 (19)
C1—C2—C3	120.2 (2)	C12—C11—S1	120.4 (2)
C2—C3—C4	112.7 (2)	C11—C12—H12A	109.5
C2—C3—H3A	109.0	C11—C12—H12B	109.5
C4—C3—H3A	109.0	H12A—C12—H12B	109.5
C2—C3—H3B	109.0	C11—C12—H12C	109.5
C4—C3—H3B	109.0	H12A—C12—H12C	109.5
H3A—C3—H3B	107.8	H12B—C12—H12C	109.5
C5—C4—C3	110.5 (2)	C2—C13—C14	131.3 (2)
C5—C4—H4A	109.5	C2—C13—H13	114.4
C3—C4—H4A	109.5	C14—C13—H13	114.4
C5—C4—H4B	109.5	C15—C14—C13	124.6 (2)
C3—C4—H4B	109.5	C15—C14—S2	108.91 (19)
H4A—C4—H4B	108.1	C13—C14—S2	126.47 (18)
C6—C5—C4	111.8 (2)	C14—C15—C16	113.8 (2)
C6—C5—H5A	109.3	C14—C15—H15	123.1
C4—C5—H5A	109.3	C16—C15—H15	123.1
C6—C5—H5B	109.3	C17—C16—C15	114.1 (2)
C4—C5—H5B	109.3	C17—C16—H16	122.9
H5A—C5—H5B	107.9	C15—C16—H16	122.9
C7—C6—C1	116.3 (2)	C16—C17—C18	129.7 (2)
C7—C6—C5	125.1 (2)	C16—C17—S2	110.30 (19)
C1—C6—C5	118.5 (2)	C18—C17—S2	120.0 (2)
C6—C7—C8	132.2 (2)	C17—C18—H18A	109.5
C6—C7—H7	113.9	C17—C18—H18B	109.5
C8—C7—H7	113.9	H18A—C18—H18B	109.5
C9—C8—C7	124.7 (2)	C17—C18—H18C	109.5
C9—C8—S1	109.08 (19)	H18A—C18—H18C	109.5
C7—C8—S1	126.15 (18)	H18B—C18—H18C	109.5
C8—C9—C10	114.2 (2)
O1—C1—C2—C13	7.8 (4)	C7—C8—C9—C10	−178.3 (2)
C6—C1—C2—C13	−171.3 (2)	S1—C8—C9—C10	−0.1 (3)
O1—C1—C2—C3	−172.7 (3)	C8—C9—C10—C11	−0.4 (3)
C6—C1—C2—C3	8.2 (3)	C9—C10—C11—C12	−178.7 (3)
C13—C2—C3—C4	−161.9 (3)	C9—C10—C11—S1	0.6 (3)
C1—C2—C3—C4	18.6 (4)	C8—S1—C11—C10	−0.6 (2)
C2—C3—C4—C5	−52.5 (3)	C8—S1—C11—C12	178.8 (2)
C3—C4—C5—C6	60.4 (3)	C1—C2—C13—C14	179.4 (2)
O1—C1—C6—C7	−2.1 (4)	C3—C2—C13—C14	−0.1 (4)
C2—C1—C6—C7	177.1 (2)	C2—C13—C14—C15	176.4 (3)
O1—C1—C6—C5	−179.6 (3)	C2—C13—C14—S2	−4.2 (4)
C2—C1—C6—C5	−0.4 (3)	C17—S2—C14—C15	−0.5 (2)
C4—C5—C6—C7	149.1 (3)	C17—S2—C14—C13	−180.0 (2)
C4—C5—C6—C1	−33.6 (3)	C13—C14—C15—C16	−179.6 (2)
C1—C6—C7—C8	−175.5 (2)	S2—C14—C15—C16	0.9 (3)
C5—C6—C7—C8	1.8 (4)	C14—C15—C16—C17	−1.1 (3)
C6—C7—C8—C9	179.8 (2)	C15—C16—C17—C18	−179.2 (3)
C6—C7—C8—S1	1.9 (4)	C15—C16—C17—S2	0.7 (3)
C11—S1—C8—C9	0.4 (2)	C14—S2—C17—C16	−0.1 (2)
C11—S1—C8—C7	178.6 (2)	C14—S2—C17—C18	179.8 (2)