Narrower HOMO-LUMO gap attained by conformational switching through peripheral polyarylation in 1,4,5,8-tetraaza-9,10-anthraquinodimethanes

Article abstract of DOI:10.1016/j.tet.2018.03.041

2,3,6,7,11,11,12,12-Octaphenyl-1,4,5,8-tetraaza-9,10-anthraquinodimethane was prepared as a sterically hindered molecule from 2,3,6,7-tetraphenyl-1,4,5,8-tetraaza-9,10-anthraquinone via bis(dibromomethylene) derivative through the quadruple Suzuki-Miyaura

Full text of DOI:10.1016/j.tet.2018.03.041

Accepted Manuscript
Narrower HOMO-LUMO gap attained by conformational switching through peripheral
polyarylation in 1,4,5,8-tetraaza-9,10-anthraquinodimethanes
Takanori Suzuki, Yusuke Ishigaki, Kazuma Sugawara, Yu Umezawa, Ryo Katoono,
Atsushi Shimoyama, Yoshiyuki Manabe, Koichi Fukase, Takanori Fukushima
PII:
S0040-4020(18)30306-5
10.1016/j.tet.2018.03.041
TET 29381
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 February 2018
Revised Date: 17 March 2018
Accepted Date: 19 March 2018
Please cite this article as: Suzuki T, Ishigaki Y, Sugawara K, Umezawa Y, Katoono R, Shimoyama A,
Manabe Y, Fukase K, Fukushima T, Narrower HOMO-LUMO gap attained by conformational switching
through peripheral polyarylation in 1,4,5,8-tetraaza-9,10-anthraquinodimethanes, Tetrahedron (2018),
doi: 10.1016/j.tet.2018.03.041.
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Narrower HOMO-LUMO gap attained by
conformational switching through peripheral
polyarylation in 1,4,5,8-tetraaza-9,10-
anthraquinodimethanes
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T. Suzuki,* Y. Ishigaki, K. Sugawara, Y. Umezawa, R. Katoono,
A. Shimoyama, Y. Manabe, K. Fukase and T. Fukushima
Department of Chemistry, Faculty of Science, Hokkaido
University, Sapporo, Japan; Department of Chemistry, Faculty
of Science, Osaka University, Toyonaka, Japan.; Laboratory for
Chemistry and Life Science, Institute of Innovative Research,
Tokyo Institute of Technology, Yokohama, Japan

1
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Tetrahedron
journal homepage: www.elsevier.com
Narrower HOMO-LUMO gap attained by conformational switching through
peripheral polyarylation in 1,4,5,8-tetraaza-9,10-anthraquinodimethanes
a,
a
a
a
a
Takanori Suzuki, * Yusuke Ishigaki, Kazuma Sugawara, Yu Umezawa, Ryo Katoono, Atsushi
b
b
b
c
Shimoyama, Yoshiyuki Manabe, Koichi Fukase and Takanori Fukushima
a
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan.
Department of Chemistry, Faculty of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
b
c
Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Kanagawa 226-8503, Japan.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
2,3,6,7,11,11,12,12-Octaphenyl-1,4,5,8-tetraaza-9,10-anthraquinodimethane was prepared as a
sterically hindered molecule from 2,3,6,7-tetraphenyl-1,4,5,8-tetraaza-9,10-anthraquinone via
bis(dibromomethylene) derivative through the quadruple Suzuki-Miyaura coupling reaction. An
X-ray analysis revealed that steric repulsion is relieved mainly by twisting the exomethylene
bonds, which is less common deformation for hindered quinodimethanes. According to the DFT
calculations, the folded geometry with bent exomethylene bonds is the metastable conformer,
and thus the nitrogen atoms at peri-positons and polyaryl substituents induce novel switching for
the preferred geometry of 9,10-anthraquinodimethane skeleton from the common bent form to
the twisted form, which causes a decrease in the HOMO-LUMO-gap energy by ca. 1 eV.
Available online
Keywords:
Azaaromatics
Strained molecule
Crystal structure
DFT calculation
Middle-molecular strategy
2
018 Elsevier Ltd. All rights reserved.
1
. Introduction
for novel functional materials based on the middle-molecular
strategy, we have designed and prepared 2,3,6,7,11,11,12,12-
octaphenyl-1,4,5,8-tetraaza-9,10-anthraquinodimethane (1a) and
Polycyclic azaaromatics consist of an attractive class of
compounds in terms of pharmaceutical points of view. Recently,
,3-diphenyl-1,4-diazaanthraquinone (I) was proven to be a
13
its tetramethoxy derivative (1b). Although we could not find
2
14
outstanding bioactivity heretofore, we found that the steric
selective lead compound for treatment of high-ploidy breast
cancer, which activates p53 and triggers apoptosis of tumor cell.
Pyridyl derivatives (II) were also found to be potent inhibitors
for p53-inducible protein phosphatase. Besides such biological
activities, the azaanthraquinones such as 1,4,5,8-
tetraazaanthraquinone (TAAQ) are attracting considerable
recent attentions in the research area of materials chemistry.
TAAQs are now considered as promising compounds as cathode
repulsion in 1 is relieved in an uncommon way of structural
1
15
deformation into a twisted form with attaining a narrow
2
HOMO-LUMO gap. Here we describe the details on their
unique molecular structures determined by X-ray analyses on 1a
and 1b as well as their spectral and redox properties, which were
discussed based on the DFT calculations on 1a as well as other
quinodimethane derivatives (2a, 3a, and 4a) with less number of
peripheral phenyl groups and/or nitrogens on the skeleton.
3,4
5
,6
6
,7
8
materials for lithium ion batteries and n-type semiconductors.
Furthermore, TAAQs have been used as important precursors to
9
generate a series of linearly extended azaacenes to be used as
10
OLED components.
In contrast to the quinone counterparts, there have been only a
11
few reports for the corresponding azaanthraquinodimethanes
although some derivatives were considered to be suitable
material for electroluminescent or electrophotographic devices as
12
shown in patent literature. In the course of our studies seeking

2
Tetrahedron
ACCEPTED MANUSCRIPT
2
. Results/Discussion
When pyrazine rings are replaced for the fused benzene rings
of 4a, the DFT calculation predicted two energy-minimized
conformers. One is the folded form (2a-F) with a large bent
angle (θ: 32.8°) and the other is the twisted form (2a-T).
Deformation of the latter is characterized by the twisting angle of
exocyclic double bond (φ: 28.2°) (Figure 1). Thus, introduction
of four nitrogen atoms at the peri-positions endows the
anthraquinodimethane skeleton with another way to reduce the
steric repulsion by twisting the exomethylene bonds, although the
2
.1. Switching of conformational preference predicted by DFT
calculation
9
,10-Anthraquinodimethanes with bulky substituents on the
exocyclic carbons are sterically congested molecules. To reduce
the steric repulsion between the exocyclic substituents and the
laterally fused rings, the molecules are forced to adopt nonplanar
16
geometries such as the folded structure (Scheme 1). A DFT
calculation (B3LYP/6-31G*) on 11,11,12,12-tetraphenyl-9,10-
anthraquinodimethane 4a showed that a folded structure (4a-F) is
the energy-minimized conformation. The deformation of folded
quinodimethanes can be quantitatively analyzed by the bent
angles (θ) in the boat-shaped central hexagon (Figure 1, Table 1).
A very large calculated value of θ (37.4°) showed that steric
repulsion is mainly relieved by bending the exomethylene bonds
in 4a-F. Twisting of the exomethylene bonds is another way to
relieve the strain, yet no twisted geometry (4a-T) was obtained as
an energy-minimized structure by the DFT calculation (Scheme
twisted conformer (2a-T) still has the higher energy (E = +3.36
kcal mol ) than the folded form (2a-F).
rel
–1
When vic-diphenyl groups are attached to each of the pyrazine
rings of 2a, the DFT calculation again predicted two energy-
minimized structures, 1a-F and 1a-T. It should be noted that the
twisted conformer 1a-T (φ: 27.4°) is now the more stable
structure and has a lower energy by 3.13 kcal mol than the
folded conformer 1a-F (θ: 34.2°). To reduce the steric repulsion
between the vic-phenyl groups, the fused pyrazine rings are
distorted into a twist-boat form, which is characterized by the
skew angle of the lateral hexagon (χ) defined as the dihedral
angle of two triangles (Figure 1). The value is larger in 1a-T
than in 1a-F (Table 1).
–
1
1
). Actually, the X-ray structure of tetramethoxy derivative 4b
showed that the molecule in crystal adopts a folded structure with
large bent angles [θ: 34.1(2)°, 33.2(2)°].
17
As shown above, the DFT calculation predicted that the
preferred conformation of anthraquinodimethane switches from
the folded form (F) to the twisted form (T) when pyrazine rings
are replaced for the fused benzene rings, to which the peripheral
phenyl groups are attached. It should be noted that nitrogen
atoms at the peri-positions are essential to make the twisted
19
conformation as an energy-minimized structure because the
calculation predicted the presence of only folded conformer for
2
,3,6,7,11,11,12,12-octaphenyl-9,10-anthraquinodimethane (3a).
2
.2. Preparation and X-ray structural analyses
2
,3,6,7-Tetraphenyl-1,4,5,8-tetraaza-9,10-anthraquinone
11a,13
(6)
was prepared by a condensation reaction of 2,3,5,6-
18
tetraamino-1,4-benzoquinone with benzil without using solvent
in 44% yield. Upon treatment of 6 with CBr and PPh3,
4
11d,13
bis(dibromomethylene) precursor (5)
yield (Scheme 2). Octaphenylated tetraazaanthraquinodimethane
1a) was obtained in 71% yield by the quadruple Suzuki-Miyaura
was prepared in 69%
(
coupling reaction of 5 with phenylboronic acid. When 4-
methoxyphenylboronic acid was used, tetramethoxy derivative
11d,13
(1b)
was also obtained in 94% yield.
Figure 1 Definition of structural parameters
Table 1. Summary of geometrical parameters
bent angle θ /°
twist angle φ /°
skew angle χ /°
a
a
1
1
1
2
1
2
3
4
a
obs (expt)
obs (expt)
14.3(1)
24.5(1)
8.8(1)
b
20.1(1), 18.8(1) 18.3(1), 11.4(1)
10.4(1), 10.1(1)
b
b
b
b
b
b
a-T (calc)
a-T (calc)
a-F (calc)
a-F (calc)
a-F (calc)
a-F (calc)
3.9
27.4
28.2
12.8
12.2
8.0
12.2
5.8
3.9
0.8
0.5
0.2
1.9
34.2
32.8
36.5
37.4
Upon recrystallization, deep purple single crystals of 1a and
b were obtained. The low-temperature X-ray analyses revealed
1
that they are sterically hindered molecules. The molecule of 1a
[monoclinic, C2/c, Z = 4] is located on a crystallographic two-
7.7
a
fold axis. The observed structure (1a ) adopts a twisted
obs
X-ray analyses were conducted at 200 K (1a) and 150 K (1b).
conformation as in the calculated structure 1a-T, and the
observed twisting angle of exomethylene bond (φ) is 24.5(1)°
b
DFT calculations were conducted at B3LYP/6-31G* level. Twisted
conformations 3a-T and 4a-T were not obtained as energy-minimized
geometries.
(
Figure 2). The bent angle [θ: 14.3(1)°] is much

3
smaller than that for predicted for the folded
A
for
C
m
C
(1
E
a-
P
F
T
).
E
T
D
he MAde
N
pe
U
nd
S
in
C
g o
R
n
I
their conformation. In both 1a and 2a, a striking
P
T
twist-boat deformation of the fused pyrazine rings is also
outstanding [χ: 8.8(1)°] as predicted for 1a-T by the DFT
calculation (Table 1).
difference is found for the HOMO-LUMO-gap energy (∆E
HOMO-
LUMO) between the twisted and folded conformers since the
twisted forms (1a-T and 2a-T) have the higher HOMOs and the
lower LUMOs compared to the folded forms (1a-F and 2a-F).
Thus, the values of ∆EHOMO-LUMO(calc) are ca. 2.5 eV for the twisted
forms (T) whereas those for the folded forms (F) are ca. 3.5 eV,
irrespective of the presence or absence of vic-diphenyl groups.
Although the phenyl groups on the pyrazine rings induce only
marginal electronic effects, those vic-diphenyl groups switch the
geometrical preference from F to T, thus inducing narrowing the
HOMO-LUMO gap of tetraazaanthraquinodimethane in 1a by ca.
In the X-ray structure of tetramethoxy derivative (1b)
[
1
triclinic, P-1, Z = 2], the twisting angles [φ: 18.2(1) and
1.4(1)°] as well as the bent angles [θ: 20.1(1) and 18.8(1)°]
suggest that the geometry in crystal (1bobs) is close to that of
twisted conformation. Again, the twist-boat deformation of the
fused pyrazine rings was observed [χ: 10.4(1), 10.1(1)°] (Figure
2
b). In this way, the theoretically predicted geometrical
preference for the twisted conformation for the polyarylated
tetraazaanthraquinodimethane (1) was experimentally verified in
the solid state by conducting the X-ray analyses on two
derivatives.
1
eV compared to 2a. This would be unique substituent effects
on the electronic structure of highly deformed molecules that can
adopt two different geometries.
(a) top view
side view
(b) top view
side view
Figure 3 HOMO, LUMO and ∆EHOMO-LUMO of 1a-F (left) and 1a-T
(right) calculated by DFT method.
Figure 2 ORTEP drawings of (a) 1a and (b) 1b determined by low-
temperature X-ray analyses. Both molecules deform into the twisted form to
reduce the steric repulsion between diarylmethylene groups and fused
pyrazine rings.
2
.3. Differences in electronic structures of twisted and folded
conformers of tetraazaanthraquinodimethanes
According to the DFT calculation (Figure 3), in both HOMO
and LUMO, the orbital coefficients in 1a are distributed all over
the tetraazaanthraquinodimethane skeleton but not so much on
the phenyl rings attached to the pyrazine rings. So that, the
electronic perturbation by the vic-diphenyl groups in 1a is
marginal, Actually, quinodimethane 2a without vic-diphenyl
groups on the pyrazine rings has quite similar MOs to those of 1a
Figure 4 HOMO, LUMO and ∆EHOMO-LUMO of 2a-F (left) and 2a-T
(
right) calculated by DFT method.
2.4. Spectral and redox properties of twisted tetraazaanthra-
quinodimethanes (1a and 1b)
In accord with the narrow HOMO-LUMO gap predicted for
a by DFT calculations, it exhibits strong absorption in the
(
Figure 4).
1
It should be noted that tetraazaanthraquinodimethanes (1a and
visible region [λ/nm (log ε) in CH Cl : 440(sh) (4.56), 367 (4.58),
2
2
2
b) are endowed with quite different electronic structures
and 261 (4.68)] in the UV-Vis spectrum (Figure 5). The end

4
Tetrahedron
absorption of the first band is 620 nm, which
eV for the optically determined value of ∆E
A
cor
C
re
C
sp
E
on
P
ds
T
to
E
2
D
.0 MA3.
NU
C
on
SCR
clu
si
onIPT
. This
HOMO-LUMO(opt)
We have revealed that the sterically hindered 11,11,12,12-
tetraaryl-9,10-anthraquinodimethanes can adopt the twisted
conformation as an energy-minimized structure when four
value is much smaller than the calculated value (∆EHOMO-
LUMO(calc)) for 1a-F (3.51 eV) but similar to that for 1a-T (2.39 eV),
showing that the polyarylated tetraazaanthraquinodimethanes 1a
also adopts the twisted conformation in solution.
1
9
nitrogen atoms are replaced for C-H at peri-positions as in 2.
Although the folded conformer is more stable than the twisted
one in 2, peripheral polyarylation through vic-diphenyl
substitution on the pyrazine rings makes the twisted
conformation more stable in 1. Despite the negligible electronic
perturbation by the attached phenyl groups, switching of the
conformational preference reduces the HOMO-LUMO-gap
energy as large as by 1 eV. This work demonstrates unique
substituent effects controlling the HOMO-LUMO gap by
inducing uncommon way of skeletal deformation to relieve steric
hindrance.
In the case of tetramethoxy derivative (1b) [λ/nm (log ε) in
CH Cl : 512 (4.35), 384 (4.46), 293 (4.69) and 255 (4.65)], the
2
2
end absorption of the first band is around 700 nm. The smaller
value for ∆EHOMO-LUMO(opt) (1.8 eV) than 1a can be accounted for
by the raised HOMO due to the electron-donating substituents.
4
. Experimental section
4
.1. 2,3,6,7-Tetraphenyl-1,4,5,8-tetraaza-9,10-anthraquinone
(6)
A mixture of 2,3,5,6-tetraamino-1,4-benzoquinone (3.36 g, 20
mmol) and benzil (20 g, 95 mmol) was ground in a mortar and
then heated at 115 °C for 3 h. After cooling, the green-black
residue was triturated with hot EtOH (100 mL x 5) and acetone
(100 mL x 3). The remaining solid (6.63 g) was dissolved in a
large volume of CH Cl , and the solution was percolated through
2
2
a pad of Al O to give a yellow powder of 6 (4.52 g, 44%), which
2
3
2 2
Figure 5 UV-Vis spectra of 1a and 1b measured in CH Cl (293 K).
was recrystallized from 1,2,4-trichlorobenzene: decomp. 403-
1
4
(
10 °C ; H NMR (400 MHz, CDCl3): δ/ppm 7.71 (8H, m), 7.45
The raised HOMO of 1b compared to that of 1a was
confirmed by electrochemical studies. The cyclic
-1
4H, m), 7.39 (8H, m); IR (KBr) ν/cm 1705, 1520, 1450, 1370,
1
320, 1230, 1200, 1120, 1030, 700, 560; LR-MS (DI): m/z 516
voltammograms of 1a and 1b showed the waves corresponding
to both oxidation and reduction processes, thus demonstrating
their electrochemical amphotericity (Figure 6). They undergo
reversible 1e-reduction to the corresponding anion radicals
whereas oxidation process is the two-electron transfer process.
As shown in Table 2, 1a and 1b have nearly the same reduction
+
(M , BP). Anal. calcd for C H N O : C, 79.05; H. 3.90; N.
34 20 4 2
1
0.83%. Found C, 78.58; H. 3.72; N. 10.86%.
4.2. 11,11,12,12-Tetrabromo-2,3,6,7-tetraphenyl-1,4,5,8-
tetraaza-9,10-anthraquinodimethane (5)
red
ox
To a solution of 2,3,6,7-tetraphenyl-1,4,5,8-tetraaza-9,10-
potential (E ) whereas the oxidation potential (E ) of 1b is far
less positive than that of 1a, as expected. The electrochemically
determined values of ∆EHOMO-LUMO(ec) are 2.00 and 1.76 V for 1a
and 1b, respectively. These small values again support the
assumption that polyarylated tetraazaanthraquinodimethanes
adopt the twisted conformation in solution.
anthraquinone 6 (105 mg, 0.193 mmol) and CBr (376 mg, 1.16
4
mmol) in dry CH Cl (24 mL) was added PPh (609 mg, 2.32
2
2
3
mmol) at 0 °C. Then, the mixture was stirred at 25 °C for 24 h.
The precipitates were removed from the solution by filtration and
washed with AcOEt. The solvent of the filtrate was removed
under reduced pressure. The crude product was purified by
column chromatography (silica gel, hexane-CH
give 5 as a colorless solid (109 mg, 69%): mp > 300 °C ; H
2
Cl (9:1)) to
2
1
NMR (400 MHz, CDCl ): δ/ppm 7.58 (8H, m), 7.34 (12H, m);
3
1
3
C NMR (100 MHz, CDCl ): δ/ppm 149.66, 143.40, 137.84,
3
-
1
1
1
1
5
8
33.02, 129.68, 129.17, 128.34, 85.89; IR (KBr) ν/cm 1978,
954, 1886, 1808, 1761, 1705, 1647, 1572, 1510, 1484, 1448,
401, 1367, 1174, 1114, 1074, 1030, 935, 815, 785, 753, 696,
81, 552, 501, 432; HR-MS (FD): calcd for C H Br N (M )
23.8422, found: 823.8431.
+
36
20
4
4
4
.3. 2,3,6,7,11,11,12,12-octaphenyl-1,4,5,8-tetraaza-9,10-
anthraquinodimethane (1a)
Figure 6 Cyclic voltammograms of 1a and 1b measured in
DMF (293 K).
A
mixture of 11,11,12,12-tetrabromo-2,3,6,7-tetraphenyl-
1
,4,5,8-tetraaza-9,10-anthraquinodimethane 5 (75 mg, 0.091
mmol), phenylboronic acid (66 mg, 0.54 mmol), K CO (97 mg,
.71 mmol) and (Ph P) Pd (5 mg, 4 µmol) in a mixture of PhMe
a
Table 2. Redox potentials of 1a and 1b
2
3
red
ox
0
E
/ V
E
(2e) / V
3 4
(
2 mL), EtOH (1.0 mL) and H O (1.0 mL) was stirred at 80 °C
2
1
1
a (R = H)
–1.12
–1.22
+0.88 (irrev.)
+0.54
for 25 h. After cooling to 25 °C, the reaction mixture was diluted
with EtOAc, washed with water and brine, dried over MgSO ,
4
b (R = OMe)
a
and concentrated under reduced pressure. The crude product was
purified by column chromatography (silica gel, CH Cl ) to give
Values were measured by cyclic voltammetry in DMF at 293 K. .
2
2

5
1
1
a as a red solid (70 mg, 71%): mp. 264-265
A
°C
C
;
C
H
E
NMPT
R
E
(4
D
00 MAN
C
U
rys
S
ta
C
l d
R
at
I
a of 1b: MF C H N O , FW 937.11, triclinic P-
64 48 4 4
P
T
MHz, CDCl ): δ/ppm 7.30-7.40 (12H, m), 7.25 (8H, m), 7.16 (4H,
1, a = 13.804(2) Å, b = 14.782(2) Å, c = 14.931(2) Å, α =
61.239(15)º, β = 68.823(17)º, γ = 68.265(16)º, V = 2417.4(7)
3
13
m), 7.05 (8H, m), 6.73 (8H, m); C NMR (100 MHz, CDCl3):
δ/ppm 151.51, 146.49, 146.32, 141.52, 137.64, 131.16, 129.75,
3
-3
Å , ρ(Z = 2) = 1.287 g cm . A total of 9347 independent
reflection (2θmax 52º) were measured at 200 K. The structure was
solved by the direct method and the atomic coordinates were
refined with anisotropic temperature factors. The position of
hydrogen atoms were calculated and included in the refinement
with isotropic temperature factors (649 parameters). The final R,
wR, and GOF values are 6.02%, 18.05%, and 0.947 respectively.
CCDC 1047046.
-
1
1
3
1
9
6
(
8
4
28.45, 128.11, 128.05, 127.68, 127.52; IR (KBr) ν/cm 3053,
023, 1948, 1887, 1804, 1593, 1580, 1552, 1514, 1484, 1443,
398, 1372, 1314, 1234, 1202, 1178, 1156, 1119, 1074, 1034,
99, 964, 942, 929, 881, 843, 818, 790, 767, 758, 732, 694, 642,
07, 601, 582, 545, 524, 503, 468; LR-MS (FD): m/z (%) 816
+
2+
+
M , bp), 408 (M , 15); HR-MS (FD): calcd for C H N (M )
16.32530, found: 816.32366; UV-Vis (CH Cl ): λ/nm (log ε)
2 2
60 40 4
40(sh) (4.56), 367 (4.58), 261 (4.68).
4
.8. Cytotoxicity assay
4
.4. 11,11,12,12-Tetrakis(4-methoxyphenyl)-2,3,6,7-
Hela cell strain (JCRB9004) was purchased from JCRB cell
tetraphenyl-1,4,5,8-tetraaza-9,10-anthraquinodimethan.e (1b)
bank (Japan). The incubation of Hela cells in this study was all
◦
A
mixture of 11,11,12,12-tetrabromo-2,3,6,7-tetraphenyl-
performed under 5% CO gas at 37 C in D-MEM low glucose
2
1
,4,5,8- tetraazaanthraquinodimethane 5 (35 mg, 0.042 mmol), 4-
medium containing L-glutamine and Phenol Red, 10% (v/v) heat-
inactivated fetal bovine serum, 1% (v/v) Penicillin-Streptomycin
Solution (×100). Cell desquamation was performed with a trypsin
(2.5 g/L) solution in PBS containing 1 mmol/L EDTA and a
small amount of phenol red as a pH indicator.
methoxyphenylboronic acid (38 mg, 0.252 mmol), K CO (450
mg, 3.36 mmol) and (Ph P) Pd (2.4 mg, 2 µmol) in a mixture of
PhMe (4.6 mL), EtOH (1.0 mL) and H O (1.0 mL) was stirred at
8
2
3
3
4
2
0 °C for 22 h. After cooling to 25 °C, the reaction mixture was
diluted with EtOAc, washed with water and brine, dried over
Hela cells were seeded in 96-well plate at a density of ca 1.0 x
10 per well and incubated 24 h. Cells were then incubated 24 h
4
MgSO , and concentrated under reduced pressure. The crude
4
product was purified by column chromatography (silica gel,
in the presence of 1a and 1b at the concentration range (0.01-1
ꢀM). To maintain the solubility of the synthetic compounds this
culture included DMSO (1%). The cell viability was measured by
using Cell Counting Kit-8 (Dojindo Molecular Technologies,
Inc., Kumamoto, Japan) assay. Cell Counting Kit-8 assay
solution (10ꢀL) was added to each well and then incubated with
for 4 h. The absorbance at 450 nm was measured by using a
multi-well plate reader (Infinite® F50/Robotic, TECAN). Non-
treated cells served as controls.
CH Cl ) to give 1b as a red solid (37 mg, 94%): mp. 250-254 °C;
2
2
1
H NMR (400 MHz, CDCl ): δ/ppm 7.18 (8H, m), 7.16 (4H, m),
3
13
7
.05 (8H, m), 6.89 (8H, m), 6.79 (8H, m), 3.89 (12H, s);
C
NMR (100 MHz, CDCl ): δ/ppm 159.9, 145.7, 141.4, 139.4,
3
-
1
1
3
1
1
;
37.8, 133.2, 129.7, 128.3, 127.7, 113.4, 55.5 ; IR (KBr) ν/cm
029, 2996, 2952, 2929, 2906, 2833, 2050, 2020, 1948, 1886,
806, 1736,1599, 1570, 1505, 1489, 1463, 1370, 1295, 1245,
201, 1172, 1118, 1093, 1031, 831, 765, 695, 598, 580, 510, 422
+
2+
LR-MS (FD): m/z (%) 936 (M , bp), 468 (M , 4); HR-MS
+
(
FD): calcd for C H N O (M ) 936.3676, found: 936.3688 ;
Acknowledgments
64
48
4
4
UV-Vis (CH Cl ): λ/nm (logε) 512 (4.35), 384 (4.46), 293
2
2
(
4.69), 255 (4.65).
.5. Computational Methods
DFT calculations were performed with the Gaussian 09 program
We thank Grant-in-Aid for Scientific Research on Innovative
Areas: "Middle molecular strategy" (No. 2707) from MEXT and
Grant-in-Aid from JSPS (Nos. 15H03790, 16K13968, 16H06591,
4
1
5K17818) Japan. This work was also supported by the
20
Research Program of “Five-star Alliance” in “NJRC Mater. &
Dev.” MEXT.
package. The geometries of the compounds were optimized
using the B3LYP method with the 6-31G* basis set. The natures
of the stationary points were assessed by means of vibration
frequency analysis.
References and notes
4
.6. Cyclic voltammetry
1
.
Choudhary, A.; Zachek, B.; Lera, R. F.; Zasadil, L. M.; Lasek, A.;
Denu, R. A.; Kim, H.; Kanugh, C.; Laffin, J. J.; Harter, J. M.;
Wisinski, K. B.; Saha, S.; Weaver, B. A.; Burkard, M. E.
Mol.Cancer Ther. 2016, 15, 48-59.
Suzuki, T.; Miyanari, S.; Tsubata, Y.; Fukushima, T.; Miyashi, T.;
Yamashita, Y.; Imaeda, K.; Ishida, T.; Nogami, T. J. Org. Chem.
2001, 66, 216-224.
Sakaguchi, K.; Imagawa, T.; Suzuki, T. unpublished results.
Yagi, H.; Chuman, Y.; Kozakai, Y.; Imagawa, T.; Takahashi, Y.;
Yoshimura, F.; Tanino, K.; Sakaguchi, K. Bioorg. Med. Chem.
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The voltammetric analyses were conducted in DMFcontaining
0
.1 M Et NClO as a supporting electrolyte (E / V vs SCE, Pt
4 4
−1
electrode, scan rate 100 mV s ). Ferrocene undergoes one-
electron oxidation at +0.44 V under the similar conditions. For
the irreversible oxidation potential, the value was calculated as
Epeak - 0.03 V.
2
.
3
4
.
.
4
.7. X-ray analyses
Crystal data of 1a: MF C H N , FW 817.00, monoclinic
60
40
4
5
.
Bock, H.; Dickmann, P.; Hermann, H. F. Zeitschr. Naturforsch. B,
C2/c, a = 16.206(3) Å, b = 9.7387(14) Å, c = 27.740(5) Å, β =
1
991, 46, 326-338.
3
-3
1
03.809(2)º, V = 4251.5(13) Å , ρ(Z = 4) = 1.276 g cm .
total of 4827 independent reflection (2θmax 55º) were measured at
50 K. The molecules are located on the crystallographic 2-fold
A
6
.
Shimizu, A.; Tujii, Y.; Kuramoto, H.; Nokami, T.; Inatomi, Y.;
Hojo, N.; Yoshida, J. Energy Technol. 2014, 2, 155-158.
1
7. Takeda, T.; Taniki, R.; Masuda, A.; Honma, I.; Akutagawa, T. J.
Pow. Sour. 2016, 328, 228-234.
8
axis. The structure was solved by the direct method and the
atomic coordinates were refined with anisotropic temperature
factors. The position of hydrogen atoms were calculated and
included in the refinement with isotropic temperature factors
.
(a) Liang, Z;. Tang, Q.; Liu, J.; Li, J.; Yan, F.; Miao, Q. Chem.
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(289 parameters). The final R, wR, and GOF values are 4.98%,
1
2.72%, and 1.063 respectively. CCDC 1822761.
9
.
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-1
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