F-type or T-type aromatic-aromatic interaction in two isoflavone derivatives

Article abstract of DOI:10.1007/s10870-007-9277-7

Two isoflavone derivatives, 5,6,7,4′-tetramethoxyisoflavone (I) and 6,4′-dimethoxy- 7-ethoxy-5-hydroxylisoflavone (II), have been synthesized and their crystal structures were determined by ¹H NMR and single crystal X-ray diffraction studies. I

Full text of DOI:10.1007/s10870-007-9277-7

J Chem Crystallogr (2008) 38:129–133
DOI 10.1007/s10870-007-9277-7
ORIGINAL PAPER
F-type or T-type Aromatic–Aromatic Interaction in Two
Isoflavone Derivatives
Zun-Ting Zhang Æ Xue-Ling Zhang
Received: 12 October 2005 / Accepted: 10 October 2007 / Published online: 27 October 2007
ꢀ Springer Science+Business Media, LLC 2007
Abstract Two isoflavone derivatives, 5,6,7,40-tetrameth-
oxyisoflavone (I) and 6,40-dimethoxy- 7-ethoxy-5-
hydroxylisoflavone (II), have been synthesized and their
risk factor for gastric cancer [1, 2]. Various animal studies
indicated that irisolidone greatly reduced the ethanol-
induced mortality [3, 4] as well as serum alanine amino-
transferase (ALT) and aspartate aminotransferase (AST)
activities [5]. Isoflavone derivatives are widely known to
be biologically active compounds. These compounds
exhibit antioxidant [6], oestrogenic, insecticidal, pesticidal
and antifungal properties [7, 8], for example, licoricone
from the root of licorice is used in the treatment of stomach
ulcers [9], aformosine is an isoflavone partly responsible
for the insect resistance of a soybean species [10, 11]. The
crystal structures of 6,7,40-trimethoxyisoflavone [12],
7-hydroxy- 40-methoxyisoflavone [13], 5,50-dihydroxy-
7,30,40-trimethoxyisoflavone [14], 5,7-dihydroxy- 40-meth-
oxy-isoflavone-quinone [15] et al had been reported. In this
paper, irisolidone as the leading compound, two isoflavone
derivatives I and II (Scheme 1) were synthesized, and their
1
crystal structures were determined by H NMR and single
crystal X-ray diffraction studies. I is triclinic, space group
˚
P-1 with a = 7.828(1) A, b = 10.285(2) A, c = 11.608(2)
˚
˚
A, a = 104.90(2)ꢁ, b = 110.546(9)ꢁ, c = 99.54(1)ꢁ and
Z = 2. II is orthorhombic, space group Pna21 with
˚
˚
˚
a = 7.0244(6) A, b = 15.0104(15) A, c = 15.7538(15) A,
and Z = 4. Molecules of I are linked into two-dimensional
structure by a combination of C–HꢀꢀꢀO hydrogen bond and
F-type aromatic–aromatic interactions. II shows some
discrepancies with I and the molecules are linked into
columns by T-type aromatic-aromatic interaction.
Keywords Isoflavone derivatives ꢀ Crystal structure ꢀ
F-type aromatic-aromatic interaction ꢀ T-type aromatic–
aromatic interaction ꢀ Hydrogen bond
1
structures were elucidated by H NMR and X-ray single
crystal diffractions.
Introduction
Experimental
Irisolidone (5,7-dihydroxy-6,40-dimethoxyisoflavone),
a
kind of isoflavone, as one of the effective components in
the flowers of Pueraia lobata, had the most potent inhibi-
tory activity against Helicobacter pylori (HP) which is a
The melting points were determined using X4 melting
1
point instrument (uncorrected). The H NMR spectra were
recorded on a Bruker AM-300 spectrometer with TMS as
internal reference and DMSO-d6 as solvent. The crystal
structures of I and II were determined using Siemens P4
four-circle diffractometer and Bruker Smart-1000 CCD
diffractometer instrument, respectively.
Z.-T. Zhang ꢀ X.-L. Zhang
Key Laboratory of Medicinal Plant Resources and Natural
Pharmaceutical Chemistry, Shaanxi Normal University,
Ministry of Education, Xi’an 710062, P.R. China
Irisolidone (1.0 g) was dissolved into acetone (30 mL)
and KOH (1 mL, 0.3%). Dimethyl sulfate (1 mL) was
added dropwise to the solution with vigorous stirring at
room temperature for 8 h. The mixture was poured into
water (40 mL), yellow precipitation appeared, which was
Z.-T. Zhang (&) ꢀ X.-L. Zhang
School of Chemistry and Materials Science, Shaanxi Normal
University, Xi’an 710062, P.R. China
e-mail: zhangzt@snnu.edu.cn
123

130
J Chem Crystallogr (2008) 38:129–133
Scheme 1
1
O
8
1
O
8
H3CO
H3CO
C2H5O
H3CO
2
2
7
7
2'
2'
1'
1'
3'
3
3'
3
6
6
4
5
4
5
6'
OCH3
O
OH
O
6'
4'
4'
OCH3
OCH3
5'
5'
filtered and washed with water until the pH of the filtrate
was 7. The resulting solid residue was recrystallized from
95% ethanol solution giving I in high yield (92%), m.p:
process of preparing II was similar to that of I, dimethyl
sulfate was substituted by diethyl sulfate, II was obtained in
1
good yield (85%), m.p: 451–453 K. H NMR (DMSO-d6,
1
454–456 K. H NMR (DMSO-d6, 300 MHz, ppm) d: 3.74
300 MHz, ppm) d: 1.39 (t, 3H, CH3–CH2O–C7), 3.74 (s,
0
(s, 3H, CH3O–C6), 3.77 (s, 3H, C0H3O–C7), 3.79 (s, 3H,
3H, CH3O–C6), 3.79 (s, 3H, CH3O–C4 ), 4.19 (q, 2H, CH3–
CH3O–C5), 3.93 (s, 3H, CH3O–C4 ), 6.970 (s, 1H, H–C8),
CH2O–C7), 6.81 (s, 1H, H–C8), 7.01 (d, 2H, J0= 8.6Hz, H–
0
0
0
0
7.02 (d, 2H, J = 09.0Hz, H–C3 and H–C5 ), 7.47 (d, 2H,
C3 and H–C5 ), 7.52 (d, 2H, J = 8.6Hz, H–C2 and H–C6 ),
8.48 (s, 1H, H–C2), 12.88 (s, 1H, HO–C5).
0
J = 9.0Hz, H–C2 and H–C6 ), 8.29 (s, 1H, H–C2). The
Table 1 Crystal data and
Compound
I
II
structure refinement for I and II
CCDC no.
285223
285224
C19H18O6
342.33
296(2) K
Empirical formula
Formula weight
Temperature
C19H18O6
342.33
299(2) K
˚
˚
Wavelength
0.71073 A
Triclinic
P-1
0.71073 A
Orthorhombic
Pna2(1)
Crystal system
Space group
˚
a = 7.828(1) A
˚
a = 7.0244(6) A
Unit cell dimensions
˚
b = 10.285(2) A
˚
b = 15.0104(15) A
˚
c = 11.608(2) A
˚
c = 15.7538(15) A
a = 104.90(2)ꢁ
b = 109.12(1)ꢁ
a = 90ꢁ
b = 90ꢁ
c = 99.54(1)ꢁ
˚
820.78(36) A
c = 90ꢁ
1661.1(3) A
–3
–3
˚
Volume
Z
2
4
Density (calculated)
Absorption coefficient
F(000)
1.385 Mg/m3
0.104 mm–1
1.369 Mg/m3
0.102 mm–1
360
720
Crystal size
0.48 · 0.36 · 0.20 mm
1.97–25.50ꢁ
0 £ h £ 9
0.38 · 0.35 · 0.16 mm
3.20–27.30ꢁ
–4 £ h £ 9
h range for data collection
Limiting indices
–11 £ k £ 11
–14 £ l £ 13
2993 [R(int) = 0.0139]
–18 £ k £ 19
–20 £ l £ 18
1936 [R(int) = 0.0613]
Independent reflections
Absorption correction
None
Full-matrix least-squares on F2
2993/0/231
Multi-scan
Full-matrix least-squares on F2
1936/1/231
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
0.960
1.019
Final R indices [I [ 2sigma(I)]
R1 = 0.0402, wR2 = 0.0891
R1 = 0.0779, wR2 = 0.0989
0.036(3)
R1 = 0.0376, wR2 = 0.0828
R1 = 0.0635, wR2 = 0.0935
0.0076(19)
Extinction coefficient
–3
–3
˚
0.129 and –0.146 e A
˚
0.172 and –0.136 e A
Largest diff. peak and hole
123

J Chem Crystallogr (2008) 38:129–133
131
Crystals of I and II suitable for X-ray diffraction anal-
ysis were obtained by slow evaporation from 95% ethanol
solution after one week at room temperature. The data were
collected with graphite-monochromated Mo Ka radiation
CCDC-285223 and CCDC-285224 contain the supple-
mentary crystallographic data for this paper. These data can
be obtained free of charge at http://www.ccdc.cam.ac.uk/
conts/retrieving.html [or from the Cambridge Crystallo-
graphic Data Centre (CCDC), 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44(0)1223-336033; email: deposit@
ccdc.cam.ac.uk].
˚
(k = 0.71073 A). The structures were 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 [16]. The crystals used for the diffraction
study showed no decomposition during data collection. The
final R values (on F2) were 0.0402 of I and 0.0376 of II.
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.
Results and Discussion
I and II both contain a benzopyranone moiety, a phenyl
moiety (Fig. 1). The atoms of benzopyranone moiety are
nearly coplanar, the dihedral angle between ring A(C1–C6)
and ring C(O1/C1/C6–C9) are 3.4ꢁ of I and 2.1ꢁ of II. To
avoid steric conflicts, the two rigid ring systems, phenyl
Table 2 Selected bond lengths
˚
O(1)–C(9)
1.341(2)
1.235(2)
1.433(2)
1.427(2)
1.414(2)
1.391(2)
1.372(2)
0.9300
O(1)–C(1)
O(3)–C(3)
O(5)–C(5)
O(6)–C(13)
C(1)–C(2)
C(2)–C(3)
C(8)–C(10)
C(16)–H(16A)
1.370(2)
1.352(2)
1.373(2)
1.365(2)
1.384(2)
1.368(3)
1.483(3)
0.9600
(A) and angles (ꢁ) for I and II
O(2)–C(7)
O(3)–C(16)
O(5)–C(18)
O(6)–C(19)
C(1)–C(6)
C(4)–C(5)
C(9)–H(9)
I
C(4)–O(4)–C(17)
O(3)–C(3)–C(2)
C(4)–C(5)–O(5)
C(1)–C(6)–C(5)
C(6)–C(7)–C(8)
C(8)–C(9)–O(1)
C(11)–C(10)–C(8)
C(15)–C(14)–H(14)
O(1)–C(2)
114.17(17)
125.37(18)
117.61(18)
115.37(17)
115.40(17)
126.27(19)
122.99(18)
119.4
O(1)–C(1)–C(2)
O(4)–C(4)–C(3)
O(5)–C(5)–C(6)
C(5)–C(6)–C(7)
C(9)–C(8)–C(10)
C(8)–C(9)–H(9)
C(11)–C(12)–H(12)
O(3)–C(16)–H(16A)
O(2)–C(8)
114.30(17)
118.87(17)
120.93(16)
124.88(16)
119.81(18)
116.9
120.2
109.5
1.371(4)
1.255(3)
0.8200
1.342(4)
1.443(4)
0.9600
O(3)–C(10)
O(4)–C(17)
O(6)–H(6)
C(1)–H(1A)
C(2)–C(7)
1.378(4)
0.9300
C(3)–C(4)
1.385(5)
1.391(4)
1.343(4)
1.391(4)
0.9600
C(3)–H(3)
C(5)–C(6)
C(6)–C(7)
1.378(4)
1.456(4)
0.9700
C(8)–C(9)
C(9)–C(10)
C(11)–C(12)
C(17)–H(17A)
II
C(18)–H(18A)
C(14)–O(4)–C(17)
H(1B)–C(1)–H(1C)
C(2)–C(3)–C(4)
C(2)–C(7)–H(7)
O(2)–C(8)–H(8)
O(2)–C(12)–C(13)
O(4)–C(17)–H(17A)
C(17)–C(18)–H(18A)
118.4(2)
109.5
C(16)–O(6)–H(6)
O(1)–C(2)–C(3)
109.5
115.0(3)
119.5
119.7(3)
120.2
C(3)–C(4)–H(4)
O(2)–C(8)–C(9)
126.2(3)
117.2(3)
123.9(3)
108.4
116.9
C(12)–C(11)–C(16)
C(13)–C(12)–C(11)
H(17A)–C(17)–H(17B)
H(18A)–C(18)–H(18C)
116.0(2)
110.1
109.5
109.5
123

132
J Chem Crystallogr (2008) 38:129–133
A being 9.7ꢁ, the methoxy group at atom C13 is also
coplanar with the ring B, the C19–O6–C13–C14 torsion
angle being 174.1ꢁ, the methoxy group at atom C4 is
almost vertical with the benzopyranone moiety, indicative
of the torsion angle C18–O4–C4–C5 = 88.4ꢁ and the
intramolecular hydrogen O5–H5ꢀꢀꢀO2 generates an S(6)
motif.
F-type aromatic- aromatic interactions along a-axis exist
in the crystal structure of I (Fig. 2). The isoflavone skeletons
are arranged in an antiparallel fashion, the ring C(O1/C1/C6–
C9) stacks with ring A(C1–C6) of one adjacent molecule.
The distance of Cg and Cg& [Symmetry code: & (–x, 1 – y,
˚
1 – z)] being 3.792 A, where Cg is the center of ring C or
ring A. Meanwhile, ring C also stacks with the benzopyra-
none moiety of the other adjacent molecule, with the distance
of Cg and Cg$ [Symmetry code: $ (1 – x, 1 – y, 1 – z)]
˚
being 3.802 A. These two kinds of aromatic p–p stacking
interactions make the molecules of I form a column along a-
axis. Furthermore, the columns are linked into sheets by the
combined action of intermolecular hydrogen bond C19–
H19CꢀꢀꢀO1* [Symmetry code: * (x, y – 1, z)], atom O1 acts
as hydrogen bond acceptor, via atom H19C to C19, the dis-
Fig. 1 The molecular structures of I and II, showing the atom-
labelling scheme. Displacement ellipsoids are drawn at the 30%
probability level. Thin dashed line indicates O–HꢀꢀꢀO intramolecular
hydrogen bond
˚
˚
tances of C19ꢀꢀꢀO1 and H19CꢀꢀꢀO1 are 3.389 A and 2.591 A,
the bond angle C19–H19CꢀꢀꢀO1 being 140.7ꢁ. Combination
of the F-type aromatic p–p stacking interactions and the
C–HꢀꢀꢀO hydrogen bonds assembles the molecules into two-
dimensional structure.
rings B(C10–C15) and benzopyranone moieties are rotated
by 136.8ꢁ of I and 134.3ꢁ of II, with respect to each other,
respectively. In the crystal structure of I, the methoxy
groups at atom C13 and atom C3 are nearly coplanar with
its attached rings, ring A and ring B, as indicated by the
torsion angles C19–O6–C13–C14 = 173.3ꢁ and C16–O3–
C3–C2 = 5.5ꢁ. Whereas, the methoxy groups at atom C5
and atom C4 are almost vertical with the benzopyranone
moiety, indicative of the torsion angle C18–O5–C5–
C4 = 91.8ꢁ and C17–O4–C4–C5 = 89.2ꢁ. In the crystal
structure of II, the ethoxyl group at atom C3 is nearly
coplanar with ring A, as indicated by the angles between
the least-squares planes defined by (O3,C16,C17) and ring
In the Fig. 3, T-type aromatic-aromatic interactions
(C–Hꢀꢀꢀp interactions) along a-axis exist in the crystal
structure of II. The distance of H15 to CgB* [Symmetry
˚
code: * (0.5 + x, 1.5 – y, z)] is 2.906 A and the distance
˚
from C15 to CgB* is 3.524 A, where CgB is the centroid of
ring B. The distance of H15 to CgB* lie in the normal
˚
range of 2.8–3.3 A [17], indicative of C–Hꢀꢀꢀp interactions.
The molecules of II are linked into columns by this T-type
aromatic–aromatic p interactions.
Fig. 2 The F-type aromatic
p–p stacking interactions and
hydrogen bonds in I. For clarity,
some H atoms have been
omitted. Symmetry codes: * x,
y – 1, z; & –x, 1 – y, 1 – z;
$ 1 – x, 1 – y, 1 – z
123

J Chem Crystallogr (2008) 38:129–133
133
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