Crystal structure of 3-Hydroxy-3′,4′-Methylenedioxy Flavone-6-Carboxylic acid Dimethylformamide solvate

Article abstract of DOI:10.1007/s10870-010-9727-5

The optically pure 3-hydroxy-3′,4′-methylenedioxy flavone-6-carboxylic acid was obtained through the chalcone route. The structure of 3-hydroxy-3′,4′-methylenedioxy flavone-6-carboxylic acid was first elucidated by single crystal X-ray analysis: triclinic

Full text of DOI:10.1007/s10870-010-9727-5

J Chem Crystallogr (2010) 40:731–734
DOI 10.1007/s10870-010-9727-5
ORIGINAL PAPER
Crystal Structure of 3-Hydroxy-30,40-Methylenedioxy
Flavone-6-Carboxylic Acid Dimethylformamide Solvate
•
Hui-Liang Wen Yun-Hua Chen Chong-Bo Liu
•
•
•
Dan-Dan Chen Xiao-Bo Hu
Received: 9 January 2008 / Accepted: 11 February 2010 / Published online: 25 February 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The optically pure 3-hydroxy-30,40-methylene-
dioxy flavone-6-carboxylic acid was obtained through the
chalcone route. The structure of 3-hydroxy-30,40-methyl-
enedioxy flavone-6-carboxylic acid was first elucidated by
single crystal X-ray analysis: triclinic, space group, tri-
histamine-induced gastric acid secretion [5], decreasing the
expanding of coronary artery [6], treating leukemia [7],
inhibiting bacterial growth [8], anti-LTD4 viral activity,
and other applications [9, 10]. Flavonoids has also been
suggested as a possible cancer chemopreventive agent on
the basis of its inhibitory effects on tumor initiation, pro-
motion, and progression [11–13].
˚
clinic (P-1) with a = 8.1379(13) A, b = 8.9831(14) A,
˚
˚
c = 13.198(2) A, a = 88.413(2)°, b = 74.908(2)°, c =
3
˚
72.987(2)°. V = 889.5(2) A , Z = 2. The structure was
Therefore, the modification of flavonoids, associated
with its interesting anticancer activity, offers promise for
the rational design of new chemotherapeutic agents. A lot
of efforts have been devoted to the study of the crystal
structure and structure-activity relationships (SAR) of the
flavonoid. In order to discover novel anti-tumor agents
with high efficiency, broad-spectrum and safety and study
their structure–activity relationships, our group prepared a
series of flavone–carboxylic acid compounds through the
chalcone route. In this paper, we describe the synthesis
and crystal structure of 3-hydroxy-30,40-methylenedioxy-
flavone-6-carboxylic acid.
solved by direct methods and refined to a final R = 0.0413
for 1630 reflections with I [ 2r(I). The crystal structure is
stabilized by O–HꢀꢀꢀO and C–HꢀꢀꢀO hydrogen bondings and
p–p stacking interactions.
Keywords Crystal structure ꢀ Synthesis ꢀ The chalcone
route ꢀ Flavone carboxylic acid
Introduction
Flavonoids, a series of benzo-g-pyrone derivatives found
ubiquitously in plants [1–4], have been reported to have
high pharmocological functions such as inhibiting the
Experimental
The title compound was synthesized by two steps. The first
step is the synthesis of 3,4-Methylenedioxy-20-hydroxy-50-
carboxychalcone; the next step is the synthesis of 30,40-
Methylenedioxy-6-carboxyflavonol, as shown in Scheme 1.
H.-L. Wen (&) ꢀ X.-B. Hu
State Key Laboratory of Food Science and Technology,
Nanchang University, Nanchang 330047,
People’s Republic of China
e-mail: hlwen70@163.com
3,4-Methylenedioxy-20-Hydroxy-50-Carboxychalcone
Y.-H. Chen ꢀ D.-D. Chen
Department of Chemistry, Nanchang University,
Nanchang 330047, People’s Republic of China
To an ice-cooled solution of 3-acetyl-4-hydroxybenzoic
acid (5.66 g, 0.0314 mol) and the required piperonal
(4.71 g, 0.0314 mol) in ethanol (50 mL) was added 25 mL
of 40% KOH and appropriate benzyl triethyl ammonium
chloride. The resulting dark red mixture was stirred at
C.-B. Liu
College of Environmental and Chemical Engineering,
Nanchang Hangkong University, Nanchang 330063,
People’s Republic of China
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Scheme 1 Synthesis scheme
for preparation of the title
compound
O
OH
CHO
OH
O
COCH3
+
O
NaOH/
O
H2O2/NaOH
O
O
HOOC
OH
COOH
O
COOH
O
O
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 84.1%.
sample of size 0.21 mm 9 0.20 mm 9 0.14 mm was
selected for the crystallographic study. All diffraction
measurements were performed at room temperature
(293 K) using graphite monochromated Mo-Ka radiation.
3-Hydroxy-30,40-Methylenedioxy Flavone-6-
Carboxylic Acid
An ice cooled mixture of 3,4-methylenedioxy-20-hydroxy-
50-carboxy chalcone (2.17 g, 0.00694 mol), NaOH (1.30 g)
in ethanol (50 mL) and H2O (25 mL), H2O2 (30%, 2.9 mL)
was stirred at 0°C for 2 h and then at ambient temperature
for 12 h. The crude product which separated on acidifi-
cation (2 N HCl) was filtered off, washed with water, and
dried. Yield 63.0%. ESI MS: 326.4 [M ? H]?.
Single crystals suitable for X-ray diffraction analysis
were recrystallized from N,N-dimethylformamide. A suitable
Table 1 Crystallographic data for the title compound
Fig. 1 The molecular structure of 3-hydroxy-30,40-methylenedioxy-
flavone-6-carboxylic acid, showing 30% probability displacement
ellipsoids
Chemical formula
CCDC deposit no.
Color/shape yellow/block
Formula weight
C20H17NO8
669948
399.35
293(2)
Triclinic
P-1
˚
Table 2 Hydrogen bonds for the compound [A and °]
Temperature (K)
Crystal system
D–HꢀꢀꢀA
d(D–H)
d(HꢀꢀꢀA)
d(DꢀꢀꢀA)
\(DHA)
O5–H5ꢀꢀꢀO4
0.82
0.82
0.82
0.93
2.21
2.06
1.80
2.51
2.67 (18)
2.80 (19)
2.60 (2)
114.9
151.8
169.6
113.7
Space group
O5–H5ꢀꢀꢀO7#1
O1–H1ꢀꢀꢀO8#2
C18–H18ꢀꢀꢀO4#4
Unit cell dimensions
˚
a(A)
8.1379(13)
8.9831(14)
13.198(2)
˚
b(A)
3.01 (28)
˚
c(A)
Symmetry transformations used to generate equivalent atoms: #1 -
x ? 1, -y ? 2, -z; #2 x - 1, y, z - 1; #3 -x, 1 - y, -z; #4 x, y,
1 ? z
a(°)
b(°)
c(°)
88.413(2)
74.908(2)
72.987(2)
3
˚
Volume (A )
889.5(2)
Z
2
Density (calculated) (g/cm3)
Absorption coefficient (mm-1
Calculated T min, T max
h range for data collection (°)
Unique reflections measured
Data/restraints/parameters
Extinction coefficient
Goodness of fit on
1.491
)
0.117
0.976, 0.989
2.37–25.50
3125
3215/0/266
0.021(2)
F2 1.018
Final R indices [I [ 2r(I)]
R indices (all data)
R1 = 0.0413, wR2 = 0.0961
R2 = 0.0646, wR2 = 0.1127
Fig. 2 A hydrogen-bonded dimer unit
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Fig. 3 A linear supramolecular chain assembled by O–HꢀꢀꢀO and C–HꢀꢀꢀO hydrogen bondings between the solvent molecules and 3-hydroxy-
30,40-methylenedioxy flavone-6-carboxylic acid molecules
The systematic absences and intensity symmetries indi-
cated the Triclinic P-1 space group.
dimers via intermolecular O5–H5ꢀꢀꢀO4 and O5–H5ꢀꢀꢀO7
(-x ? 1, -y ? 2, -z) hydrogen bondings (Fig. 2). O1–
H1ꢀꢀꢀO8 (x - 1, y, z - 1) and C18–H18ꢀꢀꢀO4 (x, y, 1 ? z)
hydrogen bondings between the solvent molecules and
3-hydroxy-30,40-methylenedioxy flavone-6-carboxylic acid
molecules join the dimers to one-dimensional molecular
ribbons (Fig. 3), and p–p stacking interactions with inter-
Semi-empirical absorption correction was applied on the
title compound using the SADABS program [14]; and the
structure was solved by direct methods using SHELXS-97
[15]. The refinement was carried out by full-matrix least-
squares method on the positional and anisotropic tempera-
ture parameters of the non-hydrogen atoms, or equivalently
corresponding to 252 crystallographic parameters. The
structure was refined to R1 = 0.0413 for observed reflec-
tions which obeyed to the condition of 3215 F0 [ 2r(F0)
and to R1 = 0.0646 for all 6192 data used in refinement
process. The maximum peaks and deepest hole observed in
the final Dq map were 0.16 and -0.215 e A-3, respectively.
The scattering factors were taken from SHELXL-97 [16].
The data collection conditions and parameters of refinement
process are listed in Table 1.
˚
planar separation distance of 3.44 A completes the crystal
structure.
Supplementary Material
CCDC 669948 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via http://www.ccdc.cam.ac.uk/conts/retrieving html, or
from the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax: (?44)1223-336-033;
or e-mail: deposit@ccdc.cam.ac.uk.32.
Results and Discussion
Acknowledgement Financial support from the National Natural
Science Foundation of China (Grant No. 20662007) is gratefully
acknowledged.
All bond lengths and angles in the title compound are
normal. Rings A, B, C,D are quite planar with the mean
˚
deviation of 0.0055, 0.0034, 0.0043, 0.0593 A respectively
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J Chem Crystallogr (2010) 40:731–734
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