(E)-1-[4-(Methyl­sulfan­yl)phen­yl]-2-(2,3,4-trimeth­oxy­phen­yl)ethene

Agnieszka Gielara-Korzańska; Tomasz Stefański; Artur Korzański; Stanisław Sobiak

doi:10.1107/S1600536812036288

. 2012 Aug 25;68(Pt 9):o2791. doi: 10.1107/S1600536812036288

(E)-1-[4-(Methylsulfanyl)phenyl]-2-(2,3,4-trimethoxyphenyl)ethene

Agnieszka Gielara-Korzańska ^a, Tomasz Stefański ^a, Artur Korzański ^b,^*, Stanisław Sobiak ^a

PMCID: PMC3435821 PMID: 22969667

Abstract

In the title compound, C₁₈H₂₀O₃S, the rings are almost coplanar [inter-ring dihedral angle = 6.6 (2)°]. In the crystal, weak C—H⋯O hydrogen bonds between the methoxy groups connect adjacent molecules, giving chains which extend along [001].

Related literature

For the synthesis, see: Cushman et al. (1991 ▶); Ulman et al. (1990 ▶). For the chemopreventive, cardioprotective and neuroprotective activity of the natural stilbene derivative trans-resveratrol (3,4′,5-trihydroxystilbene), see: Goswami & Das (2009 ▶). For preclinical and clinical studies of its therapeutic action in cancer diseases, see: Bishayee et al. (2010 ▶); Kundu & Surh (2008) ▶; Rimando & Suh (2008 ▶). For the cancer prevention activity of other natural compounds with stilbene backbones, see: Saiko et al. (2008 ▶); Rimando & Suh (2008 ▶). For similar structures, see: Sopková-de Oliveira Santos et al. (2009 ▶). For bond-length data, see: Glusker et al. (1996 ▶).

Experimental

Crystal data

C₁₈H₂₀O₃S
M _r = 316.40
Monoclinic,
a = 13.9633 (4) Å
b = 7.7094 (2) Å
c = 15.1518 (4) Å
β = 90.705 (3)°
V = 1630.95 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 293 K
0.55 × 0.5 × 0.01 mm

Data collection

Agilent Xcalibur Atlas CCD-detector diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T _min = 0.900, T _max = 1.000
8931 measured reflections
2862 independent reflections
2229 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.105
S = 1.12
2862 reflections
279 parameters
All H-atom parameters refined
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812036288/zs2220sup1.cif

e-68-o2791-sup1.cif^{(25.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812036288/zs2220Isup2.hkl

e-68-o2791-Isup2.hkl^{(140.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812036288/zs2220Isup3.cml

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
C22—H22B⋯O17ⁱ	0.93 (3)	2.72 (3)	3.505 (4)	143 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This study was supported by the Polish Ministry of Science and Higher Education grant No. N N405 209737.

supplementary crystallographic information

Comment

Chemopreventive, cardioprotective and neuroprotective activities of trans-resveratrol (3,4',5-trihydroxystilbene, RSV), the best known natural stilbene derivative, have been documented in numerous studies on animal models (Goswami & Das, 2009). Its therapeutic action in cancer diseases is also under intensive preclinical and clinical studies (Rimando & Suh, 2008; Bishayee et al., 2010; Kundu & Surh, 2008). In the last decade, other natural compounds with stilbene backbones have been shown to possess promising cancer prevention activities (Saiko et al., 2008; Rimando & Suh, 2008).

Interest in the concept and practice of chemoprevention as an approach to the control of cancer has increased especially due to the unsatisfactory results of classic chemotherapy. In vitro mechanisms of action of RSV have been extensively discussed in numerous reports and reviews. Several key mechanisms of action include: inhibition of the transcription factor NF-κB, regulation of cytochrome P450 enzymes, activation of nuclear receptors such as estrogen receptors (ERs), inhibition of expression and activity of inflammation-related enzymes such as cyclooxygenases and regulation of sirtuins. These facts lead to the conclusion that RSV might be the potential lead structure for cancer chemopreventive and chemotherapeutic compounds.

Our previous studies have shown that a series of 4'-methylthio-trans-stilbene derivatives differing in the number and position of additional methoxy groups exhibited high affinity toward active sites of CYP1 enzymes involved in the activation of procarcinogens, in particular CYP1A1, CYP1A2 and CYP1B1. 2,3,4-Trimethoxy-4'-methylthio-trans-stilbene was found to be the most selective inhibitor of the enzymes CYP1A1 and CYP1B1 (IC₅₀ values of 0.9 and 1.0 mM respectively, and exerted very low affinity to CYP1A2 (IC₅₀ value above 50 mM).

In the title compound, C₁₈H₂₀O₃S, (E)-1-(2,3,4-trimethoxyphenyl)-2-(4'-methylthiophenyl)ethene (Fig. 1a), the double bond C9—C10 in the conjugated linkage is in the trans configuration [torsion angle C(4)—C(9)—C(10)—C(11), 179.7 (2)°]. Furthermore, the value for the observed double bond [C9—C10, 1.319 (3) Å] is exactly as for the normal value (1.32 Å) and the single bonds [C(4)—C(9), 1.466 (3) Å and C(10)—C(11), 1.469 (3) Å] are shorter than the normal values (1.51 Å) (Glusker et al., 1996), indicating the formation of a weak conjugated π-electron system. The aromatic rings do not deviate significantly from a coplanar arrangement, with a dihedral angle of 6.6 (2)° between the planes. Among the three methoxy substituents on the aromatic ring, only that at C14 is approximately coplanar with the benzene ring. The other two, at C15 and C16, are oriented towards opposite sides of the ring (Fig. 1 b) (Sopková-de Oliveira Santos et al., 2009).

A very weak intermolecular contact is observed between the methoxy C22 – H22B group and atom O17ⁱ of the methoxy group of a neighbouring molecule [for symmetry code: (i), see Table 1], giving one-dimensional chains which extend along [001] (Figs. 2, 3).

Experimental

The key synthetic step for the construction of this compound involves the generation of diethyl 4-methylthiobenzyl phosphonate as an intermediate. This was prepared from commercially available 4-methylthiobenzyl alcohol in two steps. First, 4-methylthiobenzyl alcohol was converted to the chloride using SOCl₂ in toluene at room temperature. Then, through the Michaelis-Arbuzov reaction of the 4-methylthiobenzyl chloride with triethylphosphite at 130 °C the corresponding phosphonate ester was obtained (Ulman et al., 1990). The title compound was prepared by the Wittig-Horner reaction of diethyl 4-methylthiolbenzylphosphonate with the commercially available 2,3,4-trimethoxybenzaldehyde in DMF using sodium hydride as a base (Cushman et al., 1991; Ulman et al., 1990).