Polymorphism of 4′-dimethylamino-3-hydroxyflavone

Article abstract of DOI:10.1246/bcsj.20110135

Structures of two polymorphic crystals 1a and 1b of 4′ -dimethylamino-3-hydroxyflavone (1) have been determined. Each crystal has intermolecular hydrogen-bonded dimers with the adjacent molecule. The dimeric structure in crystal 1a is nearly planar, where

Full text of DOI:10.1246/bcsj.20110135

1234 Bull. Chem. Soc. Jpn. Vol. 84, No. 11, 1234-1236 (2011)
Short Articles
Polymorphism of 4¤-Dimethylamino-
3-hydroxyflavone
Kazuyuki Hino,*1 Kiyohiko Nakajima,1
Miyoko Kawahara,2 Issui Kiyota,2
and Hiroshi Sekiya2
1Department of Chemistry, Faculty of Education,
Aichi University of Education,
Figure 1. The hydrogen-bonded dimeric structure with
atomic numbering in polymorphic crystal 1a. The
intermolecular hydrogen bonds are indicated by broken
lines.
1 Hirosawa, Igaya, Kariya, Aichi 448-8542
2Department of Chemistry, Faculty of Sciences,
Graduate School of Sciences, Kyushu University,
6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581
Table 1. Hydrogen-Bond Geometry (¡, °) for Polymorphic
Crystal 1aa)
Received May 11, 2011
E-mail: khino@auecc.aichi-edu.ac.jp
D-H£A
O3-H3£O4i
D-H
H£A
D£A
D-H£A
0.89(3)
2.04(3)
2.804(3)
143(3)
a) Symmetry code: (i) ¹x + 1, ¹y + 1, ¹z + 2.
Structures of two polymorphic crystals 1a and 1b of
4¤-dimethylamino-3-hydroxyflavone (1) have been deter-
mined. Each crystal has intermolecular hydrogen-bonded
dimers with the adjacent molecule. The dimeric structure in
crystal 1a is nearly planar, whereas that in crystal 1b is
slightly bent with respect to the chromane moieties. In both
crystals there is a stacking structure of the dimers linked by
³-³ interactions.
Table 2. Selected Torsion Angles (°) for Polymorphic
Crystal 1aa)
O3-H3-O4-H3i
a) Symmetry code: (i) ¹x + 1, ¹y + 1, ¹z + 2.
175(3)
C4-C3-O3-H3
8(2)
investigate the photophysical properties of 1 and its analogs
and also their application as solid-state fluorescence sensors.
The crystal structure of 7-diethylamino-4¤-dimethylamino-3-
hydroxyflavone has been reported,6 however only PT emission
has been observed. In this paper, we report on the crystal
structure of two polymorphic crystals 1a and 1b, and compare
their structures with that of the parent molecule, 3-hydroxy-
flavone.
3-Hydroxyflavones are of great interest due to their dual
fluorescent properties, which arise from excited-state intra-
molecular charge transfer (CT) and proton transfer (PT).1,2 In
4¤-dimethylamino-3-hydroxyflavone (=2-(4-dimethylamino-
phenyl)-3-hydroxy-4H-chromen-4-one) both CT and PT emis-
sions are observed in polar solvents. The relative intensities of
the CT and PT emissions strongly depend on the chemical
and physical environment, such as the solvent polarity,
electric potential, and aggregation. It has been reported that
the introduction of an electron-donating substituent to the
4¤-position of 3-hydroxyflavones increases the fluorescence
intensity of the molecule.3 Therefore, 4¤-substituted 3-hydroxy-
flavones are promising candidates for fluorescent molecular
probes or sensors.4 Thus, 1 is a good model system for the
investigation of the CT and PT reactions, and its photophysics
has been widely studied in solution.5 1 is a flexible molecule,
since the torsional motions of the dimethylamino group and
the C-C single bond connecting the two aromatic rings are
possible. The introduction of the dimethylamino group into the
4¤-position of 3-hydroxyflavone should have a large influence
on the crystal packing and the intermolecular interactions of
3-hydroxyflavones. The subtle difference in hydrogen bonding,
dipole-dipole, and ³-³ dispersion interactions may bring
about marked changes in the fluorescence behavior of flavones.
Very recently, we have observed emission spectra of 1. Its
spectral pattern is very different from those observed in
solution. Hence, the analysis of the crystal structure is crucial to
Crystals 1a and 1b were obtained concurrently from ethanol
solution. Crystal 1a has monoclinic symmetry with space group
P21/c, and the molecules form a dimeric structure with two
identical intermolecular O-H£O hydrogen bonds. Figure 1
shows the hydrogen-bonded dimeric structure and numbering
of 1, where atoms marked with an asterisk are related by
an inversion center. The bond lengths and the bond angles
associated with the hydrogen bonds are listed in Tables 1
and 2. The bond length O3-H3 (0.89(3) ¡) is shorter than the
corresponding bond length in 3-hydroxyflavone (0.96(3) ¡).7
The crystal structure of 3-hydroxyflavone has orthorhombic
symmetry with space group P212121, in which intermolecular
hydrogen bonds link neighboring molecules to form dimers
along a twofold screw axis. The intermolecular bond distances
H3£O4i (2.04(3) ¡) and O3£O4i (2.804(3) ¡) are longer than
those in the dimeric structure of 3-hydroxyflavone (1.88(4) and
2.734(3) ¡, respectively). Only a single intermolecular hydro-
gen bond exists between the paired molecules. The crystal
packing is shown in Figure 2. The thick broken lines show
³-³ dispersion interactions and thin broken lines show short
contacts of atoms less than the sum of van der Waals radii.
Each hydroxy group forms a hydrogen bond with the carbonyl
Published on the web October 29, 2011; doi:10.1246/bcsj.20110135

K. Hino et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 11 (2011) 1235
Figure 2. The crystal packing of polymorphic crystal 1a.
The thick broken lines show ³-³ dispersion interactions
and thin broken lines show short contacts of atoms less
than the sum of van der Waals radii.
Figure 4. The crystal packing of polymorphic crystal 1b.
The thick broken lines show ³-³ dispersion interactions
and thin broken lines show short contacts of atoms less
than the sum of van der Waals radii.
Figure 3. The hydrogen-bonded dimeric structure with
atomic numbering in polymorphic crystal 1b. The
intermolecular hydrogen bonds are indicated by broken
lines.
nonequivalent. The intermolecular hydrogen-bond distance
of O3-H3£O24i (2.899(2) ¡) is longer, and that of O23-
H23£O4ii (2.629(2) ¡) is shorter than each corresponding
distance (2.734(3) ¡) in the dimeric structure of 3-hydroxy-
flavone. Nevertheless, the two intermolecular O-H£O bond
angles (154(2) and 151(3)°) are almost the same. As shown
in Figure 4, the chromane moieties that consist of the O1 and
C2-C10, and the O21 and C22-C30 atoms for the two
molecules are unsymmetrically bent, since the torsion angles
of C4-C3-O3-H3 and C24i-C23i-O23i-H23i are in-phase and
nonequivalent (Table 4). In crystal 1b there is a similar
stacking structure of the dimers to that in crystal 1a linked
by ³-³ interactions (two spacings 3.49 and 3.42 ¡ between
the adjacent chromane moieties). The torsional motion of the
dimethylamino group for the phenyl ring in crystal 1b is
blocked by the hydroxy O23£H17 and the aromatic C25£H18
interactions with both methyl C17 and C18 groups.
Table 3. Hydrogen-Bond Geometry (¡, °) for Polymorphic
Crystal 1ba)
D-H£A
D-H
H£A
D£A
D-H£A
O3-H3£O24i
O23-H23£O4ii
0.86(3)
0.83(3)
2.11(3)
1.87(3)
2.899(2)
2.629(2)
154(2)
151(3)
a) Symmetry code: (i) x, y + 1, z; (ii) x, y ¹ 1, z.
Table 4. Selected Torsion Angles (°) for Polymorphic
Crystal 1ba)
O3-H3-O4-H23i
¹173(2) C4-C3-O3-H3
¹15(2)
O23i-H23i-O24i-H3 ¹173(2) C24i-C23i-O23i-H23i ¹7(2)
a) Symmetry code: (i) x, y + 1, z.
According to the previous study,7 no intermolecular hydro-
gen-bonded dimer was observed in crystals of 2¤-methyl-3-
hydroxyflavone. The crystal structure of 2¤-methyl-3-hydroxy-
flavone shows an antiparallel-overlapped molecular arrange-
ment. For 3¤-methyl-3-hydroxyflavone, a centrosymmetric
hydrogen-bonded dimer was formed. It seems that the steric
hindrance between the hydroxy and 2¤-methyl groups interferes
with the formation of mutual hydrogen bonds between adjacent
molecules in the crystal. The dihedral angle between the phenyl
ring and the chromane ring is 5.5°, 60.5°, and 23.1° for 3-
hydroxyflavone, 2¤-methyl-, and 3¤-methyl-, respectively.7 For
1a and 1b, this angle is 29.1° and 30.5°, 33.9° which are
comparable to that for 3¤-methyl-3-hydroxyflavone. It is worth
noting that a centrosymmetric dimeric structure composed of
hydrogen bonds was observed in the crystal structures of 1.
A similar hydrogen-bonded dimer has also been reported in
the crystal structure of 4¤-fluoro-8 and 4¤-bromo-3-hydroxy-
flavone.9 Very recently, we found that the excitation of crystals
1a and 1b at 77 K using UV light provided unique emission
spectra, where five peaks appeared in the 440-570 nm region.
O atom, as shown in Figure 1. The two intermolecular
hydrogen bonds form a centrosymmetric dimeric structure.
The chromane moieties that consist of the O1 and C2-C10 and
the O1i and C2i-C10i atoms for the two molecules are nearly
planar, since the torsion angle of O3-H3-O4-H3i is close to
180°. In crystal 1a there is a stacking structure of the dimers
linked by ³-³ interactions (spacing 3.32 ¡ between the
adjacent chromane moieties). The torsional motion of the
dimethylamino group for the phenyl ring in crystal 1a is
hindered due to the van der Waals interaction between aromatic
H5 and methyl C18 atoms.
On the other hand, crystal 1b has triclinic symmetry with
ꢀ
space group P1. In this polymorphic crystal, the two crystallo-
graphically independent molecules form a dimeric structure
with two intermolecular hydrogen bonds, as shown in Figure 3.
Among the bond lengths and angles associated with the
hydrogen bonds shown in Tables 3 and 4, the most prominent
feature is that the two O-H bonds (0.86(3) and 0.83(3) ¡) are

1236 Bull. Chem. Soc. Jpn. Vol. 84, No. 11 (2011)
© 2011 The Chemical Society of Japan
Table 5. Crystallographic Data for Polymorphic Crystals
1a and 1b
by the ½ scan mode. The intensities were corrected for Lorentz
and polarization effects. Numerical absorption corrections were
also applied. The structures were solved by direct methods
(SHELXS-97)11 and expanded using Fourier techniques. The
structures were refined with full-matrix least-squares on F2. The
non-hydrogen atoms were refined anisotropically. Hydrogen
atoms were refined isotropically. All calculations were per-
formed using the CrystalStructure crystallographic software
package12 except for the refinement, which was performed
using SHELXL-97.13 Crystallographic data have been depos-
ited with Cambridge Crystallographic Data Centre: Deposition
numbers CCDC 834953 and 834954. Copies of the 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, U.K.; Fax:
+44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk).
1a
1b
Chemical formula
Formula weight
C17H15NO3
281.30
C17H15NO3
281.30
Crystal system
Space group
a/¡
b/¡
c/¡
¡/°
¢/°
£/°
V/¡3
Z
Monoclinic
P21/c
7.6180(3)
7.1072(2)
26.2302(9)
90.00
90.7300(10)
90.00
1420.06(8)
4
Triclinic
P1
ꢀ
9.8050(3)
12.1655(3)
13.1840(3)
67.2890(10)
75.5060(10)
78.7790(10)
1396.04(6)
4
T/K
®(Mo K¡)/mm
298(2)
0.091
298(2)
0.092
¹1
Crystal size/mm3
Number of measured/
independent reflections
Rint
0.30 © 0.30 © 0.02 0.50 © 0.30 © 0.25
This work was supported in part by grants from the Ministry
of Education, Culture, Sports, Science and Technology of
Japan (Special Funds for Education and Research).
14046/3253
14699/6369
0.0487
0.0273
R1(Fo) for observed data/ 0.0669/0.1368
wR2(Fo ) for all data
0.0533/0.1255
References
2
1
2
P. K. Sengupta, M. Kasha, Chem. Phys. Lett. 1979, 68, 382.
A. J. G. Strandjord, P. F. Barbara, J. Phys. Chem. 1985, 89,
Goodness of fit
1.096
1.069
2355.
3
1993, 97, 2618.
P.-T. Chou, M. L. Martinez, J. H. Clements, J. Phys. Chem.
These peaks may be associated with local minima on the S1
excited-state potential surface, which arise from the suppres-
sion of the torsional motion of the dimethylamino group and/or
the torsional motion of the C-C bond that connects the two
aromatic rings of 3-hydroxyflavone due to strong intermolec-
ular interactions in crystal.
4
A. S. Klymchenko, A. P. Demchenko, J. Am. Chem. Soc.
2002, 124, 12372.
5
6
T. C. Swinney, D. F. Kelley, J. Chem. Phys. 1993, 99, 211.
P.-T. Chou, C.-H. Huang, S.-C. Pu, Y.-M. Cheng, Y.-H. Liu,
Y. Wang, C.-T. Chen, J. Phys. Chem. A 2004, 108, 6452.
M. C. Etter, Z. Urbańczyk-Lipkowska, S. Baer, P. F.
Barbara, J. Mol. Struct. 1986, 144, 155.
M. Wera, I. E. Serdiuk, A. D. Roshal, J. Błażejowski, Acta
Crystallogr., Sect. E 2010, 66, o3122.
T. Hayashi, S. Kawai, T. Ohno, Y. Iitaka, T. Akimoto,
Chem. Pharm. Bull. 1974, 22, 1219.
10 M. A. Smith, R. M. Newmann, R. A. Webb, J. Heterocycl.
Chem. 1968, 5, 425.
11 G. M. Sheldrick, SHELXS-97, Program for the Solution of
Crystal Structures, University of Göttingen, Germany, 1997.
12 CrystalStructure 4.0: Crystal Structure Analysis Package,
Rigaku Corporation, Tokyo 196-8666, Japan, 2000-2010.
13 G. M. Sheldrick, SHELXL-97, Program for the Refinement
of Crystal Structures, University of Göttingen, Germany, 1997.
7
Experimental
Preparation of Two Polymorphic Crystals 1a and 1b.
1 was prepared as follows, according to a modified Algar-
Flynn-Oyamada method.10 p-Dimethylaminobenzaldehyde
was condensed with o-hydroxyacetophenone to yield crystals
of chalcone, which were filtered and recrystallized from ethyl
acetate. The chalcone was oxidized with hydrogen peroxide in
ethanol under basic conditions, and cyclized. The product was
recrystallized from ethanol; yellow platelets of 1a formed first,
and then orange prisms of 1b formed more slowly.
X-ray Structural Determinations. Single-crystal X-ray
diffraction measurements for 1a and 1b were made on a Rigaku
SCXmini CCD area detector with graphite monochromated
Mo K¡ radiation (Table 5). The intensity data were collected
8
9