Synthesis of 7,4′-bis-(hydroxyl)-8,3′,5′-tris- (hydroxymethyl)isoflavone and crystal structure of its ester

Article abstract of DOI:10.1007/s10870-007-9272-z

7,4′-bis-(hydroxyl)-8,3′,5′-tris-(hydroxymethyl) isoflavone (I) and its ester were synthesized and examined by IR, element analysis and ¹H NMR. The crystal of 7,4′-bis-(acetyl oxide)-8,3′,5′-tris-(acetoxymethyl)isoflavone (II) was studied by X-

Full text of DOI:10.1007/s10870-007-9272-z

J Chem Crystallogr (2008) 38:27–31
DOI 10.1007/s10870-007-9272-z
ORIGINAL PAPER
Synthesis of 7,40-Bis-(hydroxyl)-8,30,50-tris-
(hydroxymethyl)isoflavone and Crystal Structure of its Ester
Yun He Æ Li-Li Chen Æ Zun-Ting Zhang
Received: 2 December 2005 / Accepted: 9 October 2007 / Published online: 27 October 2007
Ó Springer Science+Business Media, LLC 2007
Abstract 7,40-bis-(hydroxyl)-8,30,50-tris-(hydroxymethyl)
isoflavone (I) and its ester were synthesized and examined by
IR, element analysis and H NMR. The crystal of 7,40-bis-
soybean isoflavones have good value for development and
application. However, their biological utilization rates are
low and the doses are high for their poor solubilities, which
limit their wide applications. Modifying the soybean iso-
flavones with chemical methods and enriching the species
and properties of them are not only the important tasks in
today’s research field but also the sources to find new
promising leading compounds and biologically active
components [10–13]. In this article, 7,40-bis-(hydroxyl)-8,
30,50-tris-(hydroxymethyl)isoflavone (I) and a ester-solu-
bility compound, 7,40-bis-(acetyl oxide)-8,30,50-tris-
(acetoxymethyl)isoflavone (II) were synthesized (Scheme 1),
which are the derivatives of daidzein and have potential
medical applications such as inhibiting cancer cells growth,
accelerating the formation of bone cells and balancing
women’s hormone. They were determined by IR, 1H NMR
and elemental analysis, and the ester’s crystal structure was
determined by X-ray diffraction analyses.
1
(acetyl oxide)-8,30,50-tris-(acetoxymethyl)isoflavone (II)
was studied by X-ray diffraction. (II) crystallizes in the
˚
monoclinic with space group P21/c. a = 17.987(3) A,
˚
˚
b = 17.972(3) A, c = 8.4087(11) A, b = 97.703(3)°, V =
3
2693.7(6) A and Z = 4. The molecular structure of the ester
˚
consists of a benzopyranone moiety, a phenyl moiety, two
acetyl oxides and three acetoxymethyl groups. Hydrogen
bonds and aromatic stacking interactions link the ester into a
two-dimensional structure.
Keywords 7,40-Bis-(hydroxyl)-8,30,50-tris-
(hydroxymethyl)isoflavone ꢀ 7,40-Bis-(acetyloxide)-
8,30,50-tris-(acetoxymethyl)isoflavone ꢀ Crystal structure ꢀ
p–p stacking interaction ꢀ Hydrogen bond
Introduction
Experimental
The soybean isoflavones are ubiquitous natural organic
compounds, which are the products of botanic metaboliz-
ability. They display a wide range of biological activities.
For instance, they have been pharmacologically shown
with the effects of antidysrhythmic [1], antioxidant [2, 3],
and effective in getting rid of hyperkinesias [4]. Studies
have also found daidzein effective in inhibiting cancer
cells growth [5–7], accelerating the formation of bone cells
[8] and balancing women’s hormone [9]. Therefore, the
Synthesis of 7,40-bis-(hydroxyl)-8,30,50-tris-
(hydroxymethyl)isoflavone (I)
Daidzein (1.0 g, 3.94 mmol) was dissolved into 5% NaOH
(6.4 mL), and 37% formaldehyde (1.5 mL, 19.99 mmol)
was added dropwise to the solution with vigorous stirring
and refluxed at 330 K for 5 h. The reaction mixture was
acidified with HCl (5%) until pH = 2, white precipitate
appeared. The precipitate was filtered and washed with
water until the pH of the filtrate was 7, recrystallized from
methanol giving I in high yield (92%), m.p: 492–493 K. 1H
NMR (DMSO-d6, 300 MHz, ppm) d: 4.62 (s, 4H, HO–
Y. He ꢀ L.-L. Chen ꢀ Z.-T. Zhang (&)
School of Chemistry and Materials Science, Shaanxi Normal
University, Xi’an 710062, People’s Republic of China
e-mail: zhangzt@snnu.edu.cn
0
CH2–C3 ,C5 ), 4.73 (s, 2H, HO–CH2–C8), 7.04 (d, 1H,
0
123

28
J Chem Crystallogr (2008) 38:27–31
Scheme 1 Routes of synthesis
(I) and (II)
OH
8
5
1
O
1
O
OH
2
3
8
OH
2
3
7
NaOH,HCHO
330K,5h
2'
5'
7
2'
3'
3'
4'
6
4
1'
6'
6
OH
OH
OH
4
O
1'
6'
5
O
OH
4'
5'
O
O
O
O
1
O
8
2
C5H5N (CH3CO)2O
O
7
2'
3
3'
353K,40min
O
6
4
1'
6'
5
4'
O
O
5'
O
O
O
0
0
J = 8.79 Hz, H–C5), 7.35 (s,2H, H–C3 and H–C6 ), 7.95
(d, 1H, J = 8.79 Hz, H–C6), 8.11 (s, 1H, H–C2). IR (KBr)
t: 3461, 3260, 3079, 2913, 1638, 1580, 1444, 1315, 1189,
1069, 1002, 941, 583 cm-1. Anal. calcd for C18H16O7 (%):
C 62.79, H4.7; Found C 62.76, H 5.0.
after 3 days at room temperature. The data were col-
lected with graphite-monochromated Mo Ka radiation
˚
(k = 0.71073 A). The structure was solved using direct
methods and refined by full-matrix least-squares tech-
niques. All non-hydrogen atoms were assigned anisotropic
displacement parameters in the refinement. All hydrogen
atoms were added at calculated positions and refined using
a riding model. The structures were refined on F2 using
SHELXTL-97 [14]. The crystals used for the diffraction
study showed no decomposition during data collection. The
final R values (on F2) were 0.0490 of the title compound.
The crystal data and some details of the structure deter-
mination are summarized in Table 1. The selected bond
lengths and bond angles are given in Table 2.
Synthesis of 7,40-Bis-(acetyl oxide)-8,30,50-tris-
(acetoxymethyl)isoflavone (II)
I (1.0 g) was dissolved into pyridine (5 mL) and refluxed
with acetic anhydride (5 mL) at 353 K for 40 min. The
reaction mixture was poured into ice-water (50 mL) and
white precipitation appeared. The precipitate was filtered
and washed with water. The ester (II) was obtained,
recrystallized from ethanol giving II in high yield (90%),
CCDC-291536 contains the supplementary crystallo-
graphic data for this article. These data can be obtained free
of charge at http://www.ccdc.cam.ac.uk/conts/retrieving.
html [or from the Cambridge Crystallographic Data Centre
(CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44(0)1223-336033; email: deposit@ccdc.cam.ac.uk].
1
m.p: 412–413 K. H NMR (CDCl3-d, 300 MHz, ppm) d:
0
2.08 (s, 9H, CH3–COOCH2–C8, C3 , C5 ), 2.37 (s, 3H,
0
CH3–COO–C4 ), 2.40 (s, 3H, CH3–COO–C7), 5.10 (s, 4H,
0
CH3–COOCH2–C3 , C5 ), 5.39 (s, 2H, CH3–COOCH2–C8),
0
0
0
7.24 (d, 1H, J = 8.84 Hz, H–C5), 7.66 (s,2H, H–C3 and
0
H–C6 ), 8.11 (s, 1H, H–C2), 8.36 (d, 1H, J = 8.84 Hz, H–
C6). IR (KBr) t: 3616, 3507, 3453, 3068, 2950, 2345, 1781,
1738, 1638, 1155, 1021, 904, 651, 601 cm-1. Anal. calcd
for C28H26O12 (%): C 60.65 H 4.73; Found C 60.61 H 4.77.
Results and Discussion
The crystal structure of (II) is illustrated in Fig. 1. It is
composed of a benzopyranone moiety, a phenyl moiety,
two acetyl oxides and three acetoxymethyl groups. The
atoms of benzopyranone moiety, including ring A (C4/C7–
C11) and ring C (O5/C10–C14), display an almost coplanar
configuration and with a mean deviation to the least square
X-ray Diffraction Analysis
Crystals of the ester suitable for X-ray diffraction analysis
were obtained by slow evaporation from 95% ethanol
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J Chem Crystallogr (2008) 38:27–31
29
˚
Table 1 Crystal data and structure refinement for title compound
Table 2 Selected bond lengths (A) and angles (°) for title compound
CCDC no.
291536
28H26O12
O(1)–C(2)
1.219(4)
1.316(4)
1.445(3)
1.180(4)
1.347(4)
1.402(3)
1.340(3)
1.425(3)
1.184(4)
1.366(3)
1.402(3)
1.187(3)
1.329(4)
118.8(3)
118.3(2)
118.5(2)
116.6(2)
116.6(3)
122.1(4)
126.3(4)
111.5(4)
109.9(2)
116.0(2)
123.1(2)
120.8(3)
120.9(3)
O(11)–C(21)
1.442(3)
1.215(4)
1.487(4)
1.474(5)
1.508(3)
1.494(3)
0.9700
Chemical formula
Formula weight
Temperature
C
O(2)–C(2)
O(12)–C(22)
554.49
O(2)–C(3)
C(3)–C(4)
296(2) K
O(3)–C(6)
C(5)–C(6)
˚
Wavelength
0.71073 A
Monoclinic
P21/c
O(4)–C(6)
C(17)–C(26)
Crystal system
Space group
O(4)–C(7)
C(19)–C(21)
O(7)–C(27)
C(21)–H(21A)
C(22)–C(23)
˚
a = 17.987(3) A
Unit cell dimensions
O(7)–C(26)
1.495(6)
0.9600
˚
b = 17.972(3) A
O(8)–C(27)
C(23)–H(23C)
C(24)–C(25)
˚
c = 8.4087(11) A
O(9)–C(24)
1.482(3)
0.9600
b = 97.703(3)°
2693.7(6) A
4, 1.367 mg m-3
0.114 mm-1
O(9)–C(18)
C(25)–H(25A)
C(26)–H(26A)
C(27)–C(28)
3
˚
Volume
O(10)–C(24)
O(11)–C(22)
C(2)–O(2)–C(3)
C(6)–O(4)–C(7)
C(12)–O(5)–C(11)
C(24)–O(9)–C(18)
C(22)–O(11)–C(21)
O(1)–C(2)–O(2)
O(1)–C(2)–C(1)
O(2)–C(2)–C(1)
O(2)–C(3)–C(4)
C(7)–C(4)–C(11)
C(7)–C(4)–C(3)
C(11)–C(4)–C(3)
O(3)–C(6)–O(4)
0.9700
Z, Calculated density
Absorption coefficient
F(000)
1.493(4)
111.2(4)
118.5(3)
118.2(3)
121.4(2)
117.4(2)
121.8(2)
108.9(2)
116.0(2)
121.7(4)
111.7(4)
111.4(2)
107.3(2)
110.5(3)
O(4)–C(6)–C(5)
C(4)–C(7)–O(4)
C(8)–C(7)–O(4)
C(16)–C(17)–C(26)
C(19)–C(18)–O(9)
C(18)–C(19)–C(21)
O(11)–C(21)–C(19)
O(5)–C(7)–C(6)
O(12)–C(22)–O(11)
O(11)–C(22)–C(23)
O(9)–C(24)–C(25)
O(7)–C(26)–C(17)
O(7)–C(27)–C(28)
1,160
Crystal size
0.44 mm 9 0.33 mm 9 0.20 mm
h Range for data collection
Limiting indices
1.61–25.09°
-21 B h B 17, -20 B k B 21,
-10 B l B 8
Reflections collected/unique
Completeness to h = 25.09
Absorption correction
13,598/4,782 [R(int) = 0.0293]
100.0%
Semi-empirical from equivalents
0.9821 and 0.9581
Full-matrix least-squares on F2
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
4782/0/367
1.007
Final R indices [I [ 2r (I)]
R indices (all data)
R1 = 0.0490, xR2 = 0.1425
R1 = 0.0961, xR2 = 0.1614
0.248 and -0.178 e.A-3
Largest diff. peak and hole
Fig. 1 The molecular structures
of (II), showing the atom-
labelling scheme. Displacement
ellipsoids are drawn at the 30%
probability level
123

30
J Chem Crystallogr (2008) 38:27–31
Fig. 2 The aromatic p–p
stacking interactions and
hydrogen bonds in (II). For
clarity, some H atoms have been
omitted. Symmetry codes: # x,
0.5 - y, z + 0.5; * x, 0.5 - y,
z - 0.5
Cg1*
O12*
C25*
H25B*
H23B
C23
Cg
O12
Cg1
H23B#
C25
H25B
C23#
O12#
Fig. 3 The hydrogen bonds in
(II). For clarity, some H atoms
have been omitted. Symmetry
codes: & 1 - x, y - 0.5,
0.5 - z; $ 1 - x, y + 0.5,
0.5 - z
C3$
H3B$
O10
O10&
H3B
C3
˚
plane of 0.0108 A. To avoid steric conflicts, the two rigid
ring systems, phenyl ring B (C15–C20) and benzopyranone
moiety are rotated by 39.6° with respect to each other.
Aromatic p–p stacking interactions are found in the
crystal structure of (II), consisting of a column along c-axis
(Fig. 2). Ring C of the isoflavone skeleton stacks with
C23 and H25B–C25, to generate the supramolecular syn-
thon R22 (14) ring. The structures of isoflavone are linked
layer by layer, in which up and down are connect by
bifurcated hydrogen bonds of C23#–H23B#ꢀꢀꢀO12 [Sym-
metry code: # x, 0.5 - y, z + 0.5] and C25*–H25B*ꢀꢀꢀO12
[Symmetry code: * x, 0.5 - y, z - 0.5]. The distances of
#
˚
˚
˚
ring A of its neighbouring, with CgꢀꢀꢀCg = 3.525 A,
H23B#ꢀꢀꢀO12 and H25B*ꢀꢀꢀO12 are 2.432 A and 2.465 A,
the bond angle C23#–H23B#ꢀꢀꢀO12 and H25B*–
C25*ꢀꢀꢀO12 being 157.58° and 166.84°, respectively. The
aromatic p–p stacking interactions and the hydrogen
bonds make the molecules form a column along c-axis. In
addition, atom O10& acts as a hydrogen bond donor,
via atom H3B to C3, the distances of H3BꢀꢀꢀO10& is
where Cg is the center of ring C at (x, y, z) and Cg# is the
center of ring A at (x, 0.5 - y, z + 0.5). The ring C and
the ring A are almost parallel, the ring-centroid distances
˚
lie in the normal rang of 3.3–3.8 A [15], indicative of
p-stacking interactions in the crystal structure of (II).
Atom O12 acts as a hydrogen-bond donor, via atom H23B–
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J Chem Crystallogr (2008) 38:27–31
31
Fig. 4 A packing diagram of
(II)
˚
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2.494 A, the bond angle C3–H3BꢀꢀꢀO10& being 142.43°.
Hydrogen bond C3–H3BꢀꢀꢀO10& [Symmetry code: &
(1 - x, y - 0.5, 0.5 - z)] link the column into a [101]
sheet (Fig. 3). The crystal packing of (II) is shown in
Fig. 4. A two-dimensional structure of molecule is
assembled through aromatic p–p stacking interactions and
hydrogen bonds.
Acknowledgment The authors thank the Science and Technology
Key Project of Education Ministry, P.R. China (No: 07138) for
financial support.
¨
structure solution and refinement. University of Gottingen,
Germany
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