1,2,3-Trimeth-oxy-4-[(E)-2-phenyl-vinyl]benzene and (E,E)-1,4-bis-(2,3,4- trimethoxy-phenyl)buta-1,3-diene

Article abstract of DOI:10.1107/S0108270109019702

The stilbene derivative 1,2,3-trimeth-oxy-4-[(E)-2-phenyl-vinyl]benzene, C17H18O3, (I), and its homocoupling co-product (E,E)-1,4-bis-(2,3,4-trimethoxy- phenyl)buta-1,3-diene, C22H26O6, (II), both have double bonds in trans conformations in their conjugat

Full text of DOI:10.1107/S0108270109019702

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
activities. Indeed, trans-resveratrol is known to possess anti-
oxidant and anti-inflammatory properties and is anti-
proliferative with pro-apoptotic effects (Baur & Sinclair,
2006).
ISSN 0108-2701
We have previously reported a synthesis of trans-1,2-di-
arylethenes (trans-stilbenes), compounds having potential
photoprotective properties. They were synthesized from trans-
cinnamic acids using a strategy combining Hunsdiecker-type
bromodecarboxylation and the Suzuki cross-coupling reaction
under microwave heating (Bazin et al., 2007). Bromo-
decarboxylation starting from 2,3,4-trimethoxycinnamic acid
gave the corresponding ꢁ-bromostyrene intermediate, which
allowed the Suzuki cross-coupling reaction with phenyl-
boronic acid. The desired stilbene, (I), was obtained in 71%
yield and we also observed 1,4-diarylbuta-1,3-diene (II) as an
unexpected homocoupling by-product (8% yield).
1,2,3-Trimethoxy-4-[(E)-2-phenyl-
vinyl]benzene and (E,E)-1,4-bis(2,3,4-
trimethoxyphenyl)buta-1,3-diene
a
´
Jana Sopkova-de Oliveira Santos, * Marc-Antoine
Bazin,a‡ Jean-Franc¸ois Lohier,b Laꢀıla El Kihela and Sylvain
Raulta
a
´
´
Centre d’Etudes et de Recherche sur le Medicament de Normandie (CERMN),
´
EA 3915, FR CNRS 3038 INC3M, Universite de Caen, Boulevard Becquerel, 14032
b
´
Caen, France, and Laboratoire de Chimie Moleculaire et Thio-organique, UMR
´
CNRS 6507, ENSICAEN–Universite de Caen, 14050 Caen, France
Correspondence e-mail: jana.sopkova@unicaen.fr
Received 13 March 2009
Accepted 24 May 2009
Online 6 June 2009
The stilbene derivative 1,2,3-trimethoxy-4-[(E)-2-phenylvinyl]-
benzene, C17H18O3, (I), and its homocoupling co-pro-
duct (E,E)-1,4-bis(2,3,4-trimethoxyphenyl)buta-1,3-diene,
C22H26O6, (II), both have double bonds in trans conformations
in their conjugated linkages. In the structure of stilbene (I),
the aromatic rings deviate significantly from coplanarity, in
contrast with coproduct (II), the core of which is rigorously
planar. The deviation in stilbene (I) seems to be driven by
intermolecular electrostatic interactions. Diene (II) sits on a
crystallographic inversion centre, which bisects the conjugated
linkage.
The asymmetric unit of (I) (Fig. 1a) contains one molecule
and that of (II) (Fig. 1c) contains one half-molecule, the
remainder of (II) being generated by the symmetry centre
situated at the mid-point of C8—C8i in the conjugated linkage
[symmetry code: (i) Àx, Ày, Àz].
Comment
For both compounds, the double bonds in the conjugated
linkage are in the trans configuration. Futhermore, the
observed double bonds are longer and the single bonds
Stilbenes are important core structures and their photo-
chemical (photooxygenation; Kwon et al., 1989) and photo-
physical properties [photoisomerization (Waldeck, 1991),
fluorescence (Chaudhuri & Ganguly, 1969; Singh & Kanvah,
2001) and photochromic activity (Irie et al., 1994; Lucas et al.,
1998)] have been widely studied in connection with ꢀ–ꢀ*
electronic transitions of the C C double bond. Stilbenes can
exist as two possible isomers, viz. trans-stilbene and cis-stil-
bene. The cis series, for example, is involved in combretastatin
derivatives, which display cytotoxic activities against a wide
range of human cancers (Pettit et al., 2005). Stilbenes are not
only used as dyes and in optics (lasers), but are also of interest
from a medical point of view (Heynekamp et al., 2006; Sanoh et
al., 2006; Vander Jagt & Deck, 2007).
˚
shorter (Tables 1 and 2) than the theoretical values (1.32 A for
˚
double bonds and 1.51 A for single bonds; Glusker et al.,
1994), indicating the formation of a weak conjugated ꢀ-elec-
tron system.
In the structure of stilbene (I), the aromatic rings deviate
significantly from a coplanar arrangement, with a dihedral
angle of 16.92 (3)ꢀ between the planes. The origin of this
deviation seems to be an intermolecular interaction occurring
between neighbouring molecules rather than internal steric
hindrance. A contact is observed between the benzene C11—
H11 group and atom O3ii of the methoxy group of a neigh-
1
1
1
bouring molecule [symmetry code: (iii) À + x, À y, + z],
2
2
2
with H11Á Á ÁO3iii = 2.473 (12) A, C11Á Á ÁO3 = 2.4570 (8) A
and C11—H11Á Á ÁO3iii = 173.6 (9)ꢀ. Among the three methoxy
substituents of each aromatic ring, only that at C4 is
approximately coplanar with the attached ring; the other two,
at C5 and C6, are oriented towards opposite sides of the
attached ring (Fig. 1b).
iii
˚
˚
Other natural products derived from trans-stilbenes, such as
resveratrol and its analogues, exhibit important biological
´
‡ Current address: Universite de Nantes, Nantes Atlantique Universites,
IICiMed EA 1155, UFR des Sciences Pharmaceutiques, Laboratoire de
´
´
Chimie Therapeutique, 1 rue Gaston Veil, 44035 Nantes, France.
Acta Cryst. (2009). C65, o311–o313
doi:10.1107/S0108270109019702
# 2009 International Union of Crystallography o311

organic compounds
Figure 2
A view of the stacking interactions (dashed lines) in stilbene (I). Cg1 and
Cg2 are the centroids of the C9–C14 and C1–C6 rings, respectively.
1
1
[Symmetry codes: (ii) À À x, 12 + y, 21 À z; (iii) À + x, 12 À y, 21 + z; (iv) 12 À x,
2
2
1
2
À + y, 12 À z.]
stacking interaction between the aromatic rings. C2—H2
contacts the centroid Cg1iv of a neighbouring ring [Cg1 is the
1
centroid of the C1–C6 ring; symmetry code: (iv) 12 À x, À + y,
2
iv
iv
1
2
˚
À z], with H2Á Á ÁCg1 = 2.837 (15) A and C2—H2Á Á ÁCg1 =
154.6 (11)ꢀ.
Experimental
Compounds (I) and (II) were prepared according to the literature
procedure of Bazin et al. (2007). Compound (II) was isolated as the
homocoupling by-product. Compound (I) was recrystallized from
methanol to afford pure (I) as colourless crystals (m.p. 355 K).
1H NMR (CDCl3, 400 MHz): ꢂ 3.89 (s, 3H, –OMe), 3.90 (s, 3H, –
OMe), 3.91 (s, 3H, –OMe), 6.71 (d, 1H, J = 8.8 Hz), 7.03 (d, 1H, J =
16.6 Hz), 7.24–7.37 (m, 5H), 7.51–7.53 (m, 2H); 13C NMR (CDCl3,
100 MHz): ꢂ 56.0 (–OMe), 60.9 (–OMe), 61.3 (–OMe), 107.8, 120.7,
122.9, 124.5, 126.4 (2C), 127.2, 127.9, 128.6 (2C), 137.9, 142.4, 151.7,
153.2; MS (ESI): [M + H]+ 271. Compound (II) was recrystallized by
slow evaporation of a cyclohexane–ethyl acetate mixture (9:1 v/v),
Figure 1
(a), (b) Mutually perpendicular views of (I), showing the atom-labelling
scheme. Displacement ellipsoids are drawn at the 50% probability level
and H atoms are shown as small circles of arbitrary radii. (c) The
molecular structure of (II), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii. [Symmetry code: (i)
Àx, Ày, Àz.]
The core of the structure of co-product (II) is rigorously
planar, as the two halves are related by a symmetry centre. As
in compound (I), only one of the three methoxy substituents is
approximately coplanar with the aromatic ring. The other two
are again out of the plane on opposite sides.
1
giving colourless crystals of (II) after 1 or 2 d. H NMR (CDCl3,
400 MHz): ꢂ 3.87, 3.88 and 3.89 (3 s, 18H, 6 Â –OMe), 6.41–6.54 (m,
2H), 6.63–6.70 (m, 2H), 6.87–6.90 (m, 1H), 7.12–7.23 (m, 3H); MS
(ESI): [M + H]+ 387.
In stilbene (I) there are two nearly edge-on (or T-shaped)
stacking contacts (Fig. 2), one involving each of the two
aromatic rings. Atom H14 of the unsubstituted phenyl ring is
oriented toward the centroid Cg1ii of its neighbour [Cg1 is the
Compound (I)
centroid of the C9–C14 ring; symmetry code: (ii) À À x, 12 + y,
1
2
Crystal data
À z], with H14Á Á ÁCg1ii = 2.765 (11) A and C14—
1
2
˚
3
˚
C17H18O3
Mr = 270.31
V = 1458.10 (17) A
Z = 4
H14Á Á ÁCg1ii = 136.2 (9)ꢀ. The second contact, between atom
H8 of the double-bonded fragment and the substituted
aromatic ring of a neighbour, is weak but appears to be
Monoclinic, P21=n
Mo Kꢃ radiation
ꢄ = 0.08 mmÀ1
T = 296 K
0.52 Â 0.37 Â 0.25 mm
˚
a = 10.7138 (7) A
˚
b = 7.1069 (5) A
directed; H8Á Á ÁCg2iv = 3.23 (13) A and C8—H8Á Á ÁCg2
=
iv
˚
˚
c = 19.8033 (13) A
ꢁ = 104.760 (3)ꢀ
166.7 (10)ꢀ [Cg2 is the centroid of the C1–C6 ring; symmetry
code: (iv) 12 À x, À + y, 12 À z]. As we have already described, a
1
2
Data collection
weak electrostatic H11Á Á ÁO3iii interaction is also present.
In the extended structure of co-product (II), only one
significant contact was found, which consists of a T-shaped
Bruker APEXII CCD area-detector
diffractometer
66478 measured reflections
6392 independent reflections
5406 reflections with I > 2ꢅ(I)
Rint = 0.027
ꢁ
´
o312 Sopkova-de Oliveira Santos et al.
C17H18O3 and C22H26O6
Acta Cryst. (2009). C65, o311–o313

organic compounds
Table 1
Selected bond lengths (A) for (I).
All H atoms were determined via difference Fourier maps and
refined with isotropic atomic displacement parameters [C—H =
˚
˚
0.956 (13)–1.028 (17) A].
C1—C7
C7—C8
1.4667 (8)
1.3445 (8)
C8—C9
1.4673 (8)
For both compounds, data collection: APEX2 (Bruker, 2006); cell
refinement: APEX2; data reduction: SAINT (Bruker, 2006);
program(s) used to solve structure: SHELXTL (Sheldrick, 2008);
program(s) used to refine structure: SHELXL97 (Sheldrick, 2008);
molecular graphics: ORTEP-3 (Farrugia, 1997); software used to
prepare material for publication: SHELXL97.
Table 2
Selected bond lengths (A) for (II).
˚
C1—C7
C7—C8
1.4614 (10)
1.3511 (11)
C8—C8i
1.4441 (14)
´
We thank the CRIHAN, the Region Haute-Normandie and
the European Community (FEDER) for the molecular
modelling software.
Symmetry code: (i) Àx; Ày; Àz.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FA3186). Services for accessing these data are
described at the back of the journal.
Refinement
R[F2 > 2ꢅ(F2)] = 0.038
wR(F2) = 0.122
S = 1.07
253 parameters
All H-atom parameters refined
À3
˚
Áꢆmax = 0.63 e A
À3
˚
6392 reflections
Áꢆmin = À0.22 e A
References
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Bazin, M.-A., El Kihel, L., Lancelot, J.-C. & Rault, S. (2007). Tetrahedron Lett.
48, 4347–4351.
Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin,
USA.
Compound (II)
Crystal data
Chaudhuri, M. K. & Ganguly, S. C. (1969). J. Phys. Solid State Phys. 2, 1560–
1565.
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Chemists and Biologists. New York: VCH.
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R. A., Deck, L. M. & VanderJagt, D. L. (2006). J. Med. Chem. 49, 7182–7189.
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Commun. pp. 2313–2314.
3
˚
V = 987.76 (7) A
Z = 2
C22H26O6
Mr = 386.43
Monoclinic, P21=n
Mo Kꢃ radiation
ꢄ = 0.09 mmÀ1
T = 296 K
0.32 Â 0.21 Â 0.18 mm
˚
a = 10.2899 (4) A
˚
b = 7.0186 (3) A
˚
c = 13.9897 (5) A
ꢁ = 102.138 (2)ꢀ
Data collection
Bruker APEXII CCD area-detector
diffractometer
30080 measured reflections
4333 independent reflections
3409 reflections with I > 2ꢅ(I)
Rint = 0.053
Pettit, G. R., Rhodes, M. R., Herald, D. L., Hamel, E., Schmidt, J. M. & Pettit,
R. K. (2005). J. Med. Chem. 48, 4087–4099.
Sanoh, S., Kitamura, S., Sugihara, K., Kohta, R., Ohta, S. & Watanabe, H.
(2006). J. Health Sci. 52, 613–622.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Singh, A. K. & Kanvah, S. (2001). J. Chem. Soc. Perkin Trans. 2, pp. 395–401.
Vander Jagt, D. L. & Deck, L. M. (2007). US Patent Appl. 2007249647.
Waldeck, D. H. (1991). Chem. Rev. 91, 415–436.
Refinement
R[F2 > 2ꢅ(F2)] = 0.046
wR(F2) = 0.136
S = 1.07
179 parameters
All H-atom parameters refined
À3
˚
Áꢆmax = 0.68 e A
À3
˚
4333 reflections
Áꢆmin = À0.28 e A
ꢁ
´
Acta Cryst. (2009). C65, o311–o313
Sopkova-de Oliveira Santos et al. C17H18O3 and C22H26O6 o313