Supramolecular architecture of two modifications of flavone-6,2′- dicarboxylic acid

Article abstract of DOI:10.1007/s10870-011-0125-4

Two crystalline forms of flavone-6,2′-dicarboxylic acid (fla): one N,N-dimethylformamide (DMF) solvate (modification 1) and one without any solvate molecules (modification 2), have been obtained and their structures were determined by X-ray diffraction te

Full text of DOI:10.1007/s10870-011-0125-4

J Chem Crystallogr (2011) 41:1472–1475
DOI 10.1007/s10870-011-0125-4
ORIGINAL PAPER
Supramolecular Architecture of Two Modifications
of Flavone-6,20-dicarboxylic acid
•
Hui-Liang Wen Xue Feng Chong-Bo Liu
•
•
•
Yun-Hua Chen Xiao-Bo Hu
Received: 18 September 2010 / Accepted: 7 May 2011 / Published online: 20 May 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Two crystalline forms of flavone-6,20-dicar-
boxylic acid (fla): one N,N-dimethylformamide (DMF)
solvate (modification 1) and one without any solvate mol-
ecules (modification 2), have been obtained and their
structures were determined by X-ray diffraction tech-
nique. Modification 1 crystallized in the orthorhombic
space group Pbca; and modification 2 crystallized in the
monoclinic space group P2(1)/c. In 1 and 2 fla molecules
are both joined to helix chain structures via O–HꢀꢀꢀO
hydrogen-bonds between carboxylic group of B ring and
carbonyl oxygen atom of C ring, however, in 1 helix
chains are further joined by DMF molecules; and in 2
helix chains are further linked via rich hydrogen-bonds
between fla molecules, which result in different packing
of modifications 1 and 2.
Comment
Recent years, great interests have concentrated on the
syntheses and characterization of the flavonoids [1–4]
because flavone derivatives own potential biological
activity, such as antihypertensive, antimicrobial [5], anti-
viral [6, 7], anti-hiv [8–10], anticancer [11, 12] properties.
Flavone carboxylic acids with medicinal value [13] have
also been reported, e.g., 6-carboxyl flavonoids has inhibi-
tory effect on gastric acid secretion and have anti-ana-
phylaxis function [14, 15], 3-carboxyl flavonoids can be
applied to antiphlogistic [16], 7-carboxyl flavonoids can be
used in the treatment of rheumatisants [17] and so on.
Since the varieties of biological activity, the study of
structure–activity relationship on flavonoids carboxylic
acids has been the hot spot all along, and our group have
been working on it [18]. In this article, we report the
syntheses and the supramolecular structures of two modi-
fications of flavone-6,20-dicarboxylic acid, a new flavonoid
carboxylic acid with potential medicinal value.
Keywords Flavone-6,20-dicarboxylic acid ꢀ
Modification ꢀ Hydrogen-bonding ꢀ Helix chain
Experimental
H.-L. Wen (&) ꢀ X. Feng ꢀ X.-B. Hu
State Key Laboratory of Food Science and Technology,
Nanchang University, Nanchang 330047,
People’s Republic of China
The title compound was synthesized by two steps. The first
step is the synthesis of 20-hydroxy-2,50-dicarboxychalcone;
the next step is the synthesis of flavone-6,20-dicarboxylic
acid, the synthesis route of flavone-6,20-dicarboxylic acid is
shown in Scheme 1.
e-mail: hlwen70@163.com
C.-B. Liu
College of Environmental and Chemical Engineering,
Nanchang Hangkong University, Nanchang 330063,
People’s Republic of China
The synthesis of 20-hydroxy-2,50-dicarboxychalcone
Y.-H. Chen
Department of Chemistry, Nanchang University,
Nanchang 330031, People’s Republic of China
To an ice-cooled solution of 3-acetyl-4-hydroxybenzoic
acid (5.66 g, 0.031 mol) and 2-carboxybenzaldehyde
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J Chem Crystallogr (2011) 41:1472–1475
1473
(4.71 g, 0.031 mol) in ethanol (50 mL), 40% KOH
(25 mL) and appropriate benzyl triethyl ammonium chlo-
ride were added. The resulting dark red mixture was stirred
at ambient temperature for 12 h. Thereafter, the reaction
mixture was slowly poured into excess 2 N HCl, and the
resulting yellow precipitate was filtered off, washed with
H2O, and dried. Yield 64.1%.
Table 1 Crystal data for 1 and 2
Compound
1
2
Empirical formula
Formula weight
T (K)
C17H10O6ꢀC3H7ON C17H10O6
383.35
310.25
291(2)
293(2)
Crystal system
Space group
Orthorhombic
Pbca
Monoclinic
P2(1)/c
˚
a (A)
8.449(10)
16.976(2)
25.793(3)
90
10.523(14)
8.651(12)
15.990(2)
108.7(2)
1378.7(3)
4
The synthesis of flavone-6,20-dicarboxylic acid
˚
b (A)
˚
C (A)
A mixture of 20-hydroxy-2,50-dicarboxychalcone (2.17 g,
0.007 mol), 25 mL DMSO and catalytic amount of iodine
in a three necked bottle was stirred and refluxed for 2 h.
After cooling, the mixture was poured into 100 g of ice, a
white solid was obtained. The crude product was filtered
off, washed with water, and dried, recrystallized with
N,N-dimethylformamide. Yield 88.0%. Spectrosopic anal-
ysis: 1H-NMR (DMSO-d6, 400 Hz, d, p.p.m): dH 6.69
(s, 1H, H3), dH 7.68–7.81(m, 4H, H8, H30, H40, H50), dH
7.94 (m, 1H, H60), dH 8.32 (m, 1H, H7), dH 8.63 (d, 1H,
H5), dH13.39 (s, 2H, –COOH).
b (°)
3
˚
V (A )
3699.7(8)
8
Z
h range (°)
2.40–25.49
0.105
2.69–25.50
0.115
l (mm-1
)
F(000)
Dc (mg m-3
1,600
640
)
1.376
1.495
2
-3
)
˚
Goodness-of-fit on F (e A
No. data collected
No. unique data
Rint
1.022
1.038
25,769
10,188
3,440
2,564
0.0597
0.0270
Crystals of 1 were obtained by heating the mixture of
flavone-6,20-dicarboxylic acid (0.1 g, 0.32 mmol) and N,N-
dimethylformamide (16 mL) to 363 K in water-bath until
dissolving completely. Then the solution was cooled to
room-temperature and single crystals of 1 suitable for
X-ray diffraction analysis formed after 3 days. Elemental
analysis: calculated for C17H10O6ꢀC3H7ON: C 62.66, H
4.47, N 3.65; found: C 62.39, H 4.13, N 3.36%.
R1, wR2 [I [ 2r(I)]
R1, wR2 (all data)
0.0487, 0.1183
0.0838, 0.1395
0.201, -0.191
0.0384, 0.0896
0.0561, 0.1012
0.172, -0.204
Largest diff. peak
-3
˚
and hole (e A
)
Results and Discussion
Crystals of 2 were obtained by heating the mixture of
flavone-6,20-dicarboxylic acid (0.01 g, 0.03 mmol) and
n-propanol (10 mL) in oil-bath until dissolving completely.
Then the solution was cooled to room-temperature, and
single crystals of 2 suitable for X-ray diffraction analysis
formed after 15 days. Elemental analysis: calculated for
C17H10O6: C 38.71, H 3.25; found: C 38.43, H 3.13%.
Experimental details for X-ray data collection of 1 and 2
are presented in Table 1, and the molecular structure and
the atomic numbering scheme of 1 and 2 are shown in
Fig. 1a and b, respectively. In the asymmetric unit of 1
DMF molecule is linked to flavone-6,20-dicarboxylic acid
via C(18)–H(18)ꢀꢀꢀO(2) hydrogen-bond with CꢀꢀꢀO distance
˚
of 3.16(3) A.
In 1 and 2, atoms in ring A and ring C are coplanar, and
atoms in ring B are quite planar too. All the bond lengths of
modification 1 are very close to those of 2 except that there
is little difference in C(17)–O(5) bond length of com-
X-Ray Crystallography
Two different crystalline forms of flavone-6,20-dicarbox-
ylic acid suitable for X-ray diffraction analysis were re-
pounds 1 (1.324 A) and 2 (1.308 A). The atoms of the
6-carboxylic group are coplanar with ring A in 1 and 2;
however, the atoms of the 20-carboxylic group on ring B
are not coplanar with ring B, with the largest deviation of
˚
˚
crystallized from N,N-dimethylformamide
1 and n-
propanol 2, respectively. Semi-empirical absorption cor-
rections were applied using the SADABS program [19].
The structure was solved by direct methods and refined by
full-matrix least square on F2 using the SHELXTL-97
program [20, 21]. All non-hydrogen atoms were refined
with anisotropic displacement parameters. The hydrogen
atoms were generated geometrically and treated by con-
strained refinement.
˚
˚
0.5514 A (O5) in 1 and 0.7035 A (O2) in 2, respectively.
The dihedral angle between ring C and ring B in 1 is 45.4
(66) °, and it in 2 is 40.8 (46) °, both much larger than that
in flavone-30-sulfonamide with the dihedral of 8.3(3) ° [3].
However, there are significant differences in the con-
nections of the two modifications which bring out different
packing motifs of them.
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J Chem Crystallogr (2011) 41:1472–1475
Scheme 1 Synthesis route of
flavone-6,20-dicarboxylic acid
OH
O
OH
B
CHO
O
COCH 3
+
NaOH/
EtOH
I2/DMSO
HOOC
A
C
COOH
HOOC
HOOC
O
COOH
COOH
Fig. 1 The molecular
configuration and atom-
numbering scheme for 1 (a), 2
(b), atoms are shown as 30%
probability ellipsoids
Fig. 2 View of 2-D
supramolecular structure
composed of hydrogen-bonding
helix chains (shown as spacing
filling models) along the c-axis
for 1 (a), 2 (b)
˚
Table 2 Hydrogen-bonding geometry (A and °) for 1 and 2
D–H
d(D–H)
d(HꢀꢀꢀA)
\DHA
d(DꢀꢀꢀA)
A
1
O(4)–H(4)
0.82
0.82
0.93
0.93
0.93
0.93
1.77
1.80
2.49
2.59
2.59
2.58
165.4
169.1
166.6
119.7
142.0
153.0
2.57(2)
2.61(3)
3.40(3)
3.16(3)
3.37(3)
3.46(4)
O(7) [x - 1, y, z]
O(5)–H(5)
O(2) [x - 1/2, -y ? 1/2, -z ? 1]
O(7) [-x ? 1, -y, -z ? 1]
O(2)
C(4)–H(4A)
C(18)–H(18)
C(14)–H(14)
C(19)–H(19C)
O(6) [x ? 1/2, y, -z ? 3/2]
O(3) [x ? 1/2, y, -z ? 1/2]
2
O(5)–H(5)
O(4)–H(4)
C(3)–H(3)
0.82
0.82
0.93
1.78
1.83
2.34
166.9
168.4
149.4
2.58(17)
2.64(19)
3.17(5)
O(2) [-x ? 1, y ? 1/2, -z ? 1/2]
O(6) [x - 1, -y ? 3/2, z - 1/2]
O(3) [-x ? 1, -y ? 2, -z]
In the crystal structure of 1, carboxylate oxygen atom
code: x ? 1/2, y, -z ? 1/2) hydrogen-bonds (as shown in
Table 2) join the layers to form the final supramolecular
structure of 1, as shown in Fig. 3a.
O(5) in the molecule at (x, y, z) acts as a hydrogen-bond
donor to carbonyl atom O(2) in the molecule at (x - 1/2,
-y ? 1/2, -z ? 1), leading to a hydrogen-bonding helix
chain structure; and carbonyl oxygen atom of DMF mol-
ecule O(7) acts as a hydrogen-bond acceptor to O(4)–H(4)
group in the molecule at (x - 1, y, z) and C(4)–H(4A)
group in the molecule at (-x ? 1, -y, -z ? 1), which
joins the helix chains to a 2-D layer structure, as shown in
Fig. 2a. Further C(14)–H(14)ꢀꢀꢀO(6) (symmetry code:
x ? 1/2, y, -z ? 3/2) and C(19)–H(19C)ꢀꢀꢀO3 (symmetry
Similar to 1, carboxylate oxygen atom O(5) in the ring B
at (x, y, z) acts as a hydrogen-bond donor to carbonyl atom
O(2) in the ring C at (-x ? 1, y ? 1/2, -z ? 1/2),
forming hydrogen-bonding helix chains along the b-axis in
the modification 2, as shown in Fig. 2b, which are further
joined to 2-D layer structure via O(4)–H(4)ꢀꢀꢀO(6) hydro-
gen-bonds along the c-axis. In addition, the planes of
benzopyran ring of adjacent molecules are mutual parallel,
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J Chem Crystallogr (2011) 41:1472–1475
1475
Fig. 3 a The packing diagram
for 1 viewed along the a-axis;
b The packing diagram for 2
viewed along the b-axis, the
hydrogen-bonding interactions
are represented by dashed lines
˚
the average distance between the two planes is 3.46 A, and
˚
the distance between the two ring center is 3.76 A, show-
Acknowledgments Financial support from the National Natural
Science Foundation of China (Grant No. 20662007 and 20961007),
the State Key Laboratory of Food Science and Technology of Nan-
chang University (No. SKLF-TS-200915) and the Bureau of Educa-
tion of Jiangxi Province (Grant No. GJJ09064) are gratefully
acknowledged.
ing that weak p–p aromatic interaction exit between the
phenyl rings in 2; meanwhile the carboxylate oxygen atoms
of ring A form O(3)ꢀꢀꢀH(3)–C(3) hydrogen-bonds with the
C–H of ring A in the adjacent layer with CꢀꢀꢀO distance of
˚
3.18 A; these weak interactions result in the ultimate
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