Synthesis of para - Or ortho -substituted triarylbilindiones and tetraarylbiladienones by coupled oxidation of tetraarylporphyrins

Article abstract of DOI:10.1021/jo2007994

Coupled oxidation of [tetraarylporphyrinato]iron(III) chloride carrying substituents in the ortho or para positions was performed by allowing the iron porphyrin to react with dioxygen, ascorbic acid, and pyridine to give biladienone as the major product a

Full text of DOI:10.1021/jo2007994

ARTICLE
pubs.acs.org/joc
Synthesis of para- or ortho-Substituted Triarylbilindiones and
Tetraarylbiladienones by Coupled Oxidation of Tetraarylporphyrins
Ryosuke Nakamura, Kazuhisa Kakeya, Nao Furuta, Etsuko Muta, Hiroaki Nishisaka, and Tadashi Mizutani*
Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Kyotanabe,
Kyoto 610-0321, Japan
S Supporting Information
b
ABSTRACT:
Coupled oxidation of [tetraarylporphyrinato]iron(III) chloride carrying substituents in the ortho or para positions was performed by
allowing the iron porphyrin to react with dioxygen, ascorbic acid, and pyridine to give biladienone as the major product and
bilindione as a minor one. Efforts to find reaction conditions and workup procedures to obtain bilindione improved the yields of
triarylbilindiones ranging between 2% and 19%. Electron-withdrawing substituents in the para position on the aryl groups increased
the selectivity of bilindione relative to biladienone: the isolated yields of bilindione and biladienone were 2% and 85% (OMe), 6%
and 44% (COOMe), and 7% and 28% (CN), respectively. Electronic effects of substituents affected both isolation procedures and
the spectroscopic properties of bilindiones. Tri(4-methoxyphenyl)bilindione showed a red-shifted electronic absorption compared
to unsubstituted and 4-methoxycarbonyl substituted analogues. This was ascribed to the destabilization of the HOMOꢀ1 level by
the methoxy groups.
’ INTRODUCTION
been reported. Tetraarylbiladienone is in equilibrium with
the dehydrated tetraarylbilatrienone under acidic conditions.14
Smith and co-workers reported that dodecasubstituted porphyr-
in with nonyl groups on the phenyl groups, upon chemical oxi-
dation gave tetraarylbilatrienone, which is resistant to hyd-
ration.15 Recently, Lente and Fabian16 reported kinetic studies
of the oxidation of Fe(III)TPPS with H2O2 and HSO5ꢀ, and
mass spectroscopic analysis of the products showed that the iron
complex of bilindione was formed.
Photochemical Z-E isomerization is the key reaction of
bilindione as the prosthetic group of phytochrome.2b,17 In addi-
tion to Z-E isomerization, bilindione has dynamic helical chirality
and has enantiomers owing to the framework chirality.18 Chiral
framework of bilindione was used to construct chiral relay
systems19 and used as a chiral dopant for liquid crystals.20 The
coordinating ability of bilindione to metals is also interesting,21
although only the iron complex of triarylbilindione has been
reported.16 Bilindiones with aryl groups could be employed as a
key component in materials science such as an active layer of
electronic devices, because a variety of substituents could be
introduced to the aryl groups to modify the molecular orbital
Bilindiones1 are important compounds as the prosthetic
group of photoreceptor proteins2 and an intermediate of heme
degradation.3 Natural bilindiones have substituents in the pyrrole
β-positions. In nature, bilindiones are synthesized from iron
porphyrin in the sequence of reactions catalyzed by heme
oxygenase.3 As an analogous reaction, coupled oxidation of iron
porphyrins with substituents at the pyrrole β-positions was
studied in detail by Lemberg and others.4 The reaction attracts
interest due to similarity to the heme oxygenase catalyzed
reactions.5 Coupled oxidation can be used to prepare bilindiones,
particularly symmetrically substituted ones. However, to prepare
unsymmetrically substituted bilindiones in the laboratory, multi-
step synthesis is needed to control regiochemistry.6
On the other hand, bilindiones carrying substituents in the
bridging methine carbons (meso carbon) have not been found in
nature. A number of porphyrin derivatives carrying meso substit-
uents have been reported since the preparation of meso-substi-
tuted porphyrins is straightforward.7 Oxidation of meso-sub-
stituted porphyrins has been investigated using various reagents
such as thallium or cerium salts,8 N2O4,9 NaNO2ꢀTFAꢀair,10
I2/AgClO4,11m-CPBA,12 or photochemically generated singlet
oxygen.13 These oxidation reactions gave biladienones or sub-
stituted cyclic tetrapyrroles, and formation of bilindiones has not
Received: April 18, 2011
Published: June 20, 2011
r
2011 American Chemical Society
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Scheme 1. Structures of Triarylbilindione and
Tetraarylbiladienone
The double bond configurations of (Z,Z,Z)-5,10,15-triphenylbi-
lindione (2f) were confirmed by X-ray crystallographic studies.
Here we report detailed investigations into the oxidation
reactions, focusing on the oxidation of substituted FeTPP
1aꢀe as a synthetic route to triarylbilindiones. We found that
para-substituted FeTPP 1aꢀd gave both biladienones and
bilindiones both at room temperature and under reflux condi-
tions, whereas unsubstituted FeTPP 1f gave bilindiones only
under reflux conditions. The reason for the different behaviors of
unsubstituted FeTPP and substituted FeTPP is unknown. In
addition, oxidation at room temperature afforded primarily (Z,Z,Z)-
bilindiones, whereas oxidation under reflux conditions afforded
an approximately equimolar mixture of (Z,Z,Z)- and (E,Z,Z)-
bilindiones.25 For the preparation of substituted bilindiones,
we can perform the coupled oxidation either at room tempera-
ture or at an elevated temperature. The isolated yields of (Z,Z,Z)-
bilindiones oxidized at room temperature were almost the same
as those performed under the reflux conditions. Thus, para-
substituted (Z,Z,Z)-bilindiones 2aꢀd were prepared here by coupled
oxidation at room temperature. As a typical reaction, a chloroform
solution of substituted FeTPP 1aꢀd, pyridine, and ascorbic acid was
stirred with O2 bubbling at room temperature for 1 h, the reaction
mixture was treated with acid, and then biladienone and bilindione
were formed. We examined coupled oxidation reactions of
[tetrakis(4-methoxycarbonylphenyl)porphyrinato]iron(III) chloride
1a, [tetrakis(4-dodecyloxycarbonylphenyl)porphyrinato]iron(III)
chloride 1b, [tetrakis(4-cyanophenyl)porphyrinato]iron(III)
chloride 1c, and [tetrakis(2-methoxyphenyl)porphyrinato]iron-
(III) chloride 1d to clarify the substituent effects on the reaction
(Scheme 2). These porphyrins gave the oxidized linear tetra-
pyrroles with different polarity and different hydrophobicity.
Thus reaction conditions and workup procedures such as acid
treatment conditions and chromatographic separation were
optimized for each preparation. para-Substituted bilindiones
2aꢀd, ortho-substituted bilindione 2e, and ortho-substituted
biladienone 3e are new compounds, while compounds 2f,
3aꢀd, and 3f were reported previously.14,25
energies as well as crystal packing properties.22 Bilindiones with
ortho-substituted aryl groups could be attractive candidates for a
scaffold for artificial receptors where the ortho substituents could
serve as a recognition functional group.23 The substituents in the
ortho positions could form an array of recognition groups in a
convergent fashion to construct a multipoint binding pocket.23
Since a variety of tetraarylporphyrins have been prepared so far,
coupled oxidation of tetraarylporphyrins substituted in either the
ortho, meta, or para positions should be a versatile route to this
class of compounds.
We reported that coupled oxidation of [5,10,15,20-tetraaryl-
porphyrinato]iron(III) chloride at room temperature gave
biladienone,24 whereas oxidation under reflux conditions gave
both biladienone and bilindione (Scheme 1).25 Although degra-
dation of iron tetraarylporphyrin in the presence of O2 was
reported in the literature,26 detailed investigation on the struc-
tures of degraded products of tetraarylporphyrin was not re-
ported to our knowledge. In this paper we addressed two
unresolved issues, that is, (1) conversion of a series of tetra-
arylporphyrins having substituents in the para positions to
bilindiones by coupled oxidation to investigate electronic effects
of the substituents on the reaction selectivity and the properties
of the resulting bilindiones, and (2) coupled oxidation of an
ortho-substituted tetraphenyporphyrin. First, we describe the
procedure of coupled oxidation of para-substituted tetraphenyl-
porphyrin to obtain para-substituted triarylbilindiones. We
found that electron-withdrawing groups on the aryl groups
improved the yield of bilindione, whereas electron-donating
groups improved the yield of biladienone. Electronic effects of
substituents of the phenyl rings on the electronic energy of
bilindiones were examined by use of molecular orbital calcula-
tions and UVꢀvis spectroscopy. We also attempted to cleave
tetra(o-methoxyphenyl)porphyrin and we obtained both bila-
dienone and bilindione carrying ortho substituents in a fair to
good yield.
The most difficult aspect of the linear tetrapyrrole synthesis via
coupled oxidation is the fact that several products of various
oxidation levels and their Z-E isomers were formed during the
oxidation,25 so that the development of efficient separation of
these was necessary. Biladienone was the most nonpolar com-
pounds among the products, thus chromatographic separation of
the mixture on silica gave biladienone as the first fraction.
Separation of biladienone was straightforward, and it was ob-
tained in yields ranging 15ꢀ70%. Bilindione is much more polar
than biladienone, and the polarity of bilindione is similar to that
of a few byproducts. Separation of bilindione from these by-
product was tedious for some bilindiones. Careful chromato-
graphic separation on a neutral silica gel column afforded
bilindiones. Use of alumina column gave efficient separation of
tri(4-methoxyphenyl)bilindione 2d from a red byproduct with
similar polarity.
The dipole moments calculated with ab initio MO (B3LYP/6-
311+G(d,p)) were 6.6 D, 1.1 D, 5.7 D, and 4.1 D for 2a, 2c, 2d,
and 2f, respectively. The dipole moments are displayed in
Figure 1. Dipole moments of 2a, 2d, and 2f are on the pseudo-
plane of the tetrapyrroles, while that of 2c is out of plane. The
electron-withdrawing substituents, cyano groups, on the aryl
rings counteract the original dipole moment of the bilindione
core. Bilindione 2d having the electron-donating substituents
is rather polar, and elution from the silica gel column was slow.
’ RESULTS AND DISCUSSION
Bilindione Synthesis from [Tetraarylporphyrinato]iron(III)
Chloride. In preliminary studies, we found that [5,10,15,20-
tetraphenylporphyrinato]iron(III) (FeTPP, 1f) can undergo
oxidative cleavage at room temperature to yield a linear tetra-
pyrrole, biladienone 3f, in the presence of O2, ascorbic acid, and
pyridine in chloroform.25 We also reported that heating the
reaction mixture under reflux afforded the further oxidized linear
tetrapyrrole, bilindione 2f, as a minor product. Under reflux
conditions, both (Z,Z,Z)-bilindione and (E,Z,Z)-bilindione
were obtained in a ca. 1:1 ratio, and both isomers were isolated
and characterized by 1H NMR, MS, and UVꢀvis spectroscopy.
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Scheme 2. Coupled Oxidation of [Tetraarylporphyrinato]iron(III) Chloridea
a Conditions: (a) ascorbic acid, O2, pyridine, rt, 1 h; (b) 2 M HCl or 2 M HCl + TFA.
Figure 1. Dipole moments determined with ab initio molecular orbital calculations at B3LYP/6-311+G(d,p).
The isolated yields of bilindione were 6%, 19%, 7%, and 2% for
2a, 2b, 2c, and 2d, respectively. Although these yields were not
satisfactory, a single-step synthesis and no report on other
synthetic routes to this class of compounds make the reaction
worth studying.
There is a clear tendency in yields of bilindiones and
biladienones that the yields of biladienones increased as the
substituents on the aryl groups are electron-donating, while
the yields of bilindiones increased as the substituents are
electron-withdrawing. The yields of para-substituted arylbila-
dienones were 85% (OMe), 59% (H), 44% (COOMe), and
28% (CN).14 The isolated yields of para-substituted aryl
bilindiones were 2% (OMe), 4% (H), 6% (COOMe), and
7% (CN) (see Table 1). For the preparation of bilindiones, use
of tetraarylporphyrin carrying electron-withdrawing groups is
preferred.
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ARTICLE
Structures of these compounds were confirmed by 1H NMR,
ide did not proceed owing to the steric hindrance of the o-methyl
groups.25 We attempted to cleave iron tetraarylporphyrin carry-
ing one ortho substituent in each phenyl group. The coupled
oxidation of [tetra(2-methoxyphenyl)porphyrinato]iron(III)
chloride 1e proceeded smoothly to afford both biladienone 3e
(14% yield) and bilindione 2e (10% yield).
1
1D-difference NOE, 2D-NMR (1Hꢀ H COSY and HMBC),
13C NMR, and mass spectroscopy. Within the NMR time scale,
bilindione has C2 symmetry due to the rapid NH proton
1
exchange between the B-ring and the C-ring, and thus the H
NMR pattern was simple. Characteristic signals of bilindiones
were four doublets appearing in the region 6.1ꢀ7.0 ppm, which
were assigned to the pyrrole β-protons. The configurations of the
double bonds of all bilindiones were assigned to Z,Z,Z because
NMR patterns of the bilindiones were similar to those of (Z,Z,Z)-
2e whose structure was confirmed by X-ray crystallography.25
Acid Treatment of the Reaction Mixture. The reaction
mixture just after the reaction of iron porphyrin with O2, ascorbic
acid, and pyridine was dark brown. When acid was added, the
mixture turned gradually dark blue, indicating that the iron was
replaced with proton and π-conjugated linear tetrapyrroles were
produced. The acid treatment procedure also affected the yield of
bilindiones and biladienones. As an acid, we attempted to use
hydrochloric acid, sulfuric acid, trifluoroacetic acid, and a com-
bination of these. Treatment of the chloroform solution of the
reaction mixture with HClaq or H2SO4aq in a two-phase system
was a mild process and suitable for preparation of 2a, 2c, 2d, 3a,
3c, and 3d. The reaction rate was very slow for hydrophobic sub-
strate such as 1b, and the color change was incomplete. There-
fore addition of trifluoroacetic acid was necessary to prepare 2b
and 3b. For other cases, however, use of HCl or H2SO4 gave
better yields of products.
Decrease in the absorbance in the Soret band of FeTPP
followed the first order kinetics in the presence of pyridine,
ascorbic acid, and O2 in chloroform. The rate of bleaching of the
Soret band of the iron tetraarylporphyrin depended on the
concentration of pyridine. In the absence of pyridine, the
bleaching rate was very low. For unsubstituted tetraphenylpor-
phyrin and para-substituted tetraphenylporphyrins, the rate
increased with increasing pyridine concentrations and saturated
at the pyridine concentration of ca. 1.5 M.14 In contrast, bleaching
of the Soret band of [tetra(2-methoxyphenyl)porphyrinato]-
iron(III) chloride 1e proceeded fastest when the concentration
of pyridine was 0.13 M, and the bleaching reaction was inhibited
at higher pyridine concentrations (Figure 2). We used 0.25 M
pyridine for coupled oxidation of 1e and 2 M pyridine for
coupled oxidation of other iron porphyrins.
Molecular Orbital Energy Levels and UVꢀvis Absorption
Spectra of Bilindiones. For application of bilindiones to elec-
tronic and optical functional materials, control of the frontier
molecular orbital energy by substituents should be important.
Electronic effects of substituents introduced in the aryl rings on
the electronic structure of bilindiones were examined by molec-
ular orbital studies. In Table 2, molecular orbital energies
calculated by PM327 and HF/6-31(D)28 are listed. When the
orbital energies of HOMOꢀ1, HOMO, LUMO, and LUMO+1
are compared between 2a and 2f, the COOMe groups in 2a
stabilized the energies of all of these MOs to a similar extent, so
that the optical excitation energy of 2a is expected to be similar to
that of 2f. In contrast, the MeO groups in 2d destabilized the
Coupled Oxidation of ortho-Substituted [Tetraarylpor-
phyrinato]iron(III) Chloride. We previously reported that
coupled oxidation of [tetramesitylporphyrinato]iron(III) chlor-
Table 1. Isolated Yields of Bilindiones and Biladienones
Carrying Substituents in the para or ortho Positions of the
5,10,15-Aryl Groups (2aꢀf, 3aꢀf)
substituents in the
yield of bilindiones
yield of biladienones
aryl groups
2 (%)
3 (%)
p-OMe
Ha
2
4c
6
85b
59c
44b
41
p-COOMe
p-COO(CH2)11CH3
p-CN
19
7
28c
o-OMe
10
14
a Reaction with O2 was carried out under reflux conditions for bilindione
synthesis. The yield of the (Z,Z,Z)-isomer is shown, although consider-
able amounts of Z,Z,E-isomer were also formed. For para- or ortho-
substituted bilindiones, coupled oxidation was performed at room
temperature, and only (Z,Z,Z)-isomers were isolated. b Taken from ref
14. c The yields of 2f, 3f, and 3c are different from those reported in ref
25. The yields listed here are more reliable according to the repeated
synthesis.
Figure 2. Bleaching rate of [tetra(2-methoxyphenyl)porphyrinato]iron
1e versus pyridine concentrations.
Table 2. Energy Levels (eV) of Frontier Molecular Orbitals Calculated by PM3 and HF/6-31G(D)
PM3
2a (COOMe)
HF/6-31G(D)
2f (H)
2d (OMe)
2c (CN)
2f (H)
2d (OMe)
2a (COOMe)
2c (CN)
HOMOꢀ1
HOMO
ꢀ8.823
ꢀ8.023
ꢀ3.271
ꢀ2.640
ꢀ8.735
ꢀ8.020
ꢀ3.270
ꢀ2.623
ꢀ9.206
ꢀ8.370
ꢀ3.659
ꢀ3.044
ꢀ9.404
ꢀ8.720
ꢀ2.155
ꢀ1.359
ꢀ8.152
ꢀ6.819
0.643
ꢀ7.850
ꢀ6.724
0.719
ꢀ8.415
ꢀ6.819
0.643
ꢀ8.855
ꢀ7.467
ꢀ0.050
1.328
LUMO
LUMO+1
1.983
2.041
1.983
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Table 3. Absorption Maxima and Oscillator Strength of Bilindiones Obtained by Molecular Orbital Calculationsa
λmax/nm (oscillator strength)
coefficients of CI (%)
λmax/nm (oscillator strength)
coefficients of CI (%)
2f (H)
379 (1.250)
HOMOꢀ1 to LUMO (64%)
HOMO to LUMO+1 (26%)
HOMOꢀ1 to LUMO (52%)
HOMO to LUMO+1 (38%)
HOMOꢀ1 to LUMO (65%)
HOMO to LUMO+1 (22%)
HOMO to LUMO+1 (83%)
570 (0.257)
HOMOꢀLUMO (94%)
2d (OMe)
2a (COOMe)
2c (CN)
385 (1.368)
380 (1.218)
332 (0.468)
568 (0.262)
572 (0.267)
438 (0.657)
HOMOꢀLUMO (94%)
HOMOꢀLUMO (94%)
HOMOꢀLUMO (96%)
a Calculated by MOS-F program, CNDO/S3 CI(20,20).
of these bilindiones by using MOS-F indicated that the
absorption maximum of 2f was 379 nm as compared to that
of 2d at 385 nm (Table 3). According to the configuration
interaction (CI) calculations, the higher energy band at around
400 nm consists of the mixture of excitations from HOMOꢀ1
to LUMO and HOMO to LUMO+1, while the lower energy
band at around 600 nm consists of mainly excitation from
HOMO to LUMO. The CI calculation of 2c gave completely
different assignment from other bilindiones. The origin of the
discrepancy between the CI calculation and the observed
spectra for 2c is not known. As shown in Figure 4, the
HOMOꢀ1 energy level of 2d was destabilized compared to
2a, 2c, and 2f, and this explains the red-shift of the higher
energy band of 2d. Figure 3 also shows that 2e having methoxy
groups in the ortho position showed similar absorption maxima
to those of 2f. According to the optimized structures by HF/6-
31G(D), the phenyl groups in 2e were nearly perpendicular to
the dipyrromethane plane: the dihedral angles of pyrrole-R,
meso carbon, phenyl 1C and phenyl 2C were ꢀ73°, ꢀ74°, and
ꢀ72°. The dihedral angles of other bilindiones 2a, 2c, 2d, and
2f were ꢀ49°, ꢀ51°, ꢀ53° for 2a, ꢀ66°, ꢀ59°, ꢀ75° for 2c,
ꢀ53°, ꢀ48°, ꢀ50° for 2d, and ꢀ54°, ꢀ51°, and ꢀ51° for 2f,
allowing π-electrons to partially delocalize between the aryl
groups and the bilin core. The difference in the dihedral angles
can explain the fact that the o-methoxy groups in 2e have minor
electronic effects on the molecular orbitals localized on the
bilin core, and thus the effects on the UVꢀvis spectrum were
undetectable.
Figure 3. UVꢀvis spectra of bilindiones 2a, 2c, 2d, 2e, and 2f in CHCl3.
The absorption maxima were 399 and 626 nm (2a), 400 and 631 nm
(2c), 419 and 632 nm (2d), 394 and 613 nm (2e), and 400 and 616 nm
(2f).
’ CONCLUSIONS
Triarylbilindiones with either COOMe, COOC12H25, CN, or
OMe in the para position of the aryl groups were prepared by the
coupled oxidation of the corresponding iron porphyrin in yields
ranging from 2% to 19%. There was a tendency that the electron-
withdrawing groups favor formation of bilindione, whereas
electron-donating groups favor formation of biladienone. The
substituents in the para positions affected polarity of the oxidized
products, and thus isolation procedures and the properties of
bilindiones were dependent on the substituents. In particular, the
substituents in the para position affected the frontier molecular
orbital energies of bilindione π-orbitals, and these were con-
firmed by MO calculations and UVꢀvis spectroscopic studies.
Triarylbilindione and tetraarylbiladienone carrying one o-OMe
group in each aryl group were also prepared similarly by coupled
oxidation. The reactions demonstrated that the coupled oxida-
tion of tetraarylporphyrin can be extended to the derivatives with
ortho substituents.
Figure 4. Relative energies of LUMO and HOMOꢀ1 for four bilin-
diones 2f, 2d, 2a, and 2c calculated at HF/6-31G(D). In order to
compare the excitation energy, the energy levels referenced to the
HOMO level are shown.
HOMOꢀ1 energy, whereas they do not affect the energies of
other MOs to a significant extent. This explains the red-shift in
the optical absorption of 2d involving the HOMOꢀ1 molecular
orbital (vide infra).
Figure 3 shows UVꢀvis spectra of five bilindiones, 2a, 2c,
2d, 2e, and 2f, in chloroform. Solutions of 2a, 2b, 2c, 2e, and 2f
were blue, while that of 2d was greenish blue. The higher
energy band of the UVꢀvis spectra of 2d was red-shifted by
21 nm from 399 to 420 nm. The molecular orbital calculations
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’ EXPERIMENTAL SECTION
phenylene), 8.04 (d, J = 8.45 Hz, 4H, phenylene), 8.15 (d, J = 8.45 Hz,
2H, phenylene). 13C NMR (125 MHz, chloroform-d): δ 171.4, 153.3,
143.2, 139.0, 137.7, 130.2, 124.7, 121.9 ppm. MS (MALDI-TOF): m/z
1195 [M+]. HRMS (FAB): calcd for C76H98O8N4 m/z 1194.7385,
found 1194.7380. UVꢀvis spectrum: λmax (εmax) 326 nm (1.50 ꢁ 104
Mꢀ1 cmꢀ1), 403 nm (2.22 ꢁ 104 Mꢀ1 cm ꢀ1), 628 nm (1.05 ꢁ 104
Molecular orbital calculations were performed using MOPAC 3.0 Pro
(Fujitsu Ltd.) and Gaussian 09 (Gaussian Inc.).28 Commercially avail-
able reagents were used as received. Chromatographic separations of
bilindiones were performed using silica gel 60N, spherical neutral with
particle size 40ꢀ50 μm, Kanto Chemical Company. Iron porphyrins
were prepared by refluxing a DMF solution of porphyrin and iron(II)
M
ꢀ1 cm ꢀ1).
1
chloride for 4 h. Assignments of H NMR and 13C NMR were per-
(4Z,9Z,15Z)-5,10,15-Tri(4-cyanophenyl)-(21H,23H,24H)-
1
1
1,19,21,24-tetrahydro-1,19-bilindione (2c). Chloroform (600 mL)
was placed in a 2-L two-necked flask, and O2 was bubbled for 30 min.
[5,10,15,20-Tetra(4-cyanophenyl)porphyrinato]iron(III) chloride 1c (455
mg, 0.567 mmol), ascorbic acid (6.25 g, 3.52 ꢁ 10ꢀ2 mol), and pyridine
(75.2 mL, 0.92 mol) were added, and the mixture was stirred at room
temperature for 2 h with O2 bubbling. The reaction was quenched by
adding 2 M HCl (600 mL), and the solution was stirred for 2 h. The
chloroform solution was washed with water four times, and the organic layer
was dried over Na2SO4. After Na2SO4 was filtered off, the organic layer was
evaporated to give a mixture of biladienone, bilindione, and other pigments.
Bilindione was isolated by silica gel column chromatography eluted with
chloroform/acetone (15/1). Further purification by silica gel column
(chloroform/acetone, 10:1) yielded 24.1 mg (6.7%) of bilindione 2c. 1H
NMR (500 MHz, chloroform-d): δ 6.33 (d, J = 5.80 Hz, 2H, pyrrole H-2),
6.50 (d, J = 4.35 Hz, 2H, pyrrole H-7), 6.70 (d, J = 4.35 Hz, 2H, pyrrole
H-8), 7.01 (d, J = 5.80 Hz, 2H, pyrrole H-3), 7.51 (d, 4H, J = 8.00 Hz, 5,15-
phenylene), 7.64 (d, J = 7.95 Hz, 2H, 10-phenylene), 7.70 (d, J = 8.00 Hz,
4H, 5,15-phenylene), 7.82 (d, J = 7.95 Hz, 10-phenylene. 13C NMR (125
MHz, chloroform-d) δ171.0, 153.2, 143.1, 140.5, 137.6, 132.3, 125.2, 122.3.
MS (MALDI-TOF): m/z 634 [MH+]. HRMS (FAB): calcd for
C40H23O2N7 m/z 633.1913, found 633.1901. UVꢀvis spectrum: λmax
(εmax) 400 nm (2.59 ꢁ 104 Mꢀ1 cmꢀ1), 631 nm (1.26 ꢁ 104 Mꢀ1 cmꢀ1) .
(4Z,9Z,15Z)-5,10,15-Tri(4-methoxyphenyl)-(21H,23H,24H)-
1,19,21,24-tetrahydro-1,19-bilindione (2d). Chloroform (600 mL)
was placed in a 2-L two-necked flask, and O2 was bubbled for 30 min.
[5,10,15,20-Tetra(4-methoxyphenyl)porphyrinato]iron(III) chloride 1d
(494.4 mg, 0.600 mmol), ascorbic acid (5.49 g, 3.09 ꢁ 10ꢀ2 mol), and
pyridine (68.4 mL, 0.84 mol) were added, and the mixture was stirred at
room temperature for 4 h with O2 bubbling. The reaction was quenched by
adding 2 M HCl (900 mL), and the solution was stirred for 2 h. The
chloroform solution was washed with water four times, and the organic layer
was dried over Na2SO4. After Na2SO4 was filtered off, the organic layer was
evaporated to give a mixture of biladienone, bilindione, and other pigments.
Bilindione was isolated by silica gel column chromatography eluted with
chloroform/acetone (30/1). Further purification by preparative silica gel
TLC (chloroform/acetone, 20:1) yielded 7.7 mg (1.9%) of bilindione 2d.
1H NMR (500 MHz, chloroform-d): δ 3.77 (s, 6H, CH3), 3.90 (s, 3H,
CH3), 6.20 (d, J = 5.0 Hz, 2H, pyrrole H-2), 6.50 (d, J = 4.0 Hz, 2H, pyrrole
H-7), 6.77 (d, J = 4.0 Hz, 2H, pyrrole H-8), 6.87 (d, J = 10.0 Hz, 4H, 5,15-
phenylene H-30), 6.99 (overlapped two doublets, 4H, pyrrole H-3 and
5-phenylene H-30), 7.29 (d, J = 10.0 Hz, 4H, 5,15-phenylene H-20), 7.47
(d, J = 10.0 Hz, 2H, 10-phenylene H-20). 13C NMR (125 MHz, chloroform-d)
δ 171.6, 153.3, 143.3, 139.8, 138.1, 130.1, 123.7, 121.3 ppm. MS (MALDI-
TOF): m/z 649 [MH+]. HRMS (FAB): calcd for C40H32O5N4 m/z
648.2373, found 648.2373. UVꢀvis spectrum: λmax (εmax) 419 nm (2.35 ꢁ
104 Mꢀ1 cmꢀ1), 632 nm (1.08 ꢁ 104 Mꢀ1 cm ꢀ1) .
formed using Hꢀ H COSY, NOESY, 1D-differential NOE spectra,
HMBC, and HSQC spectra. Preparation and spectroscopic data of
biladienones 3a, 3c, 3d, and 3f and bilindione 2f were reported
elsewhere.24,25
(4Z,9Z,15Z)-5,10,15-Tri(4-methoxycarbonylphenyl)-(21H,-
23H,24H)-1,19,21,24-tetrahydro-1,19- bilindione (2a). Chloro-
form (300 mL) was placed in a 1-L three-necked flask, and O2 was
bubbled for 30 min. [5,10,15,20-Tetra(4-methoxycarbonylphenyl)por-
phyrinato]iron(III) chloride 1a (1.5 g), ascorbic acid (5.7 g), and pyridine
(66 mL) were added, and the mixture was stirred at room temperature for
1 h with O2 bubbling. The reaction was quenched by adding 2 M HCl
(500 mL), and the solution was stirred for 1 h at room temperature. The
chloroform solution was separated and washed with water twice, and the
organic layerwas driedoverNa2SO4. After the Na2SO4 wasfilteredoff, the
organic layer was evaporated to give a mixture of biladienone, bilindione,
and other pigments. Bilindione was isolated by silica gel column chroma-
tography eluted with chloroform/acetone (95:5). Further purification by
silica gel column chromatography using dichloromethane/acetone (17:3)
followed by silica gel column chromatography using chloroform yielded
69 mg (5.9%) of bilindione. 1H NMR (500 MHz, chloroform-d): δ 3.85
(s, 6H, CH3), 3.97 (s, 3H, CH3), 6.26 (d, J = 5.8 Hz, 2H, pyrrole H-2),
6.47 (d, J = 4.55 Hz, 2H, pyrrole H-7), 6.69 (d, J = 4.55 Hz, 2H, pyrrole
H-8), 6.94 (d, J = 5.8 Hz, 2H, pyrrole H-3), 7.45 (d, J = 8.45 Hz, 4H, 5,15-
phenylene H-20), 7.60 (d, J = 8.40 Hz, 2H, 10-phenylene H-20), 8.04 (d,
J = 8.45 Hz, 4H, 5,15-phenylene H-30), 8.17 (d, J = 8.45 Hz, 2H, 10-
phenylene H-30). 13C NMR (125 MHz, chloroform-d): δ 171.4, 153.2,
143.1, 139.0, 138.2, 130.2, 124.8, 121.8 ppm. MS (MALDI-TOF): m/z
732 [M+]. HRMS (FAB): calcd for C43H32O8N4 m/z 732.2220, found
732.2198. UVꢀvis spectrum: λmax (εmax) 328 nm (2.56 ꢁ 104
Mꢀ1 cmꢀ1), 399 nm (3.86 ꢁ 104 Mꢀ1 cm ꢀ1), 626 nm (2.08 ꢁ 104
M
ꢀ1 cm ꢀ1).
(4Z,9Z,15Z)-5,10,15-Tri(4-dodecyloxycarbonylphenyl)-
(21H,23H,24H)-1,19,21,24-tetrahydro-1,19-bilindione (2b).
Chloroform (100 mL) was placed in a 500-mL three-necked flask, and
O2 was bubbled for 30 min. [5,10,15,20-Tetra(4-dodecyloxycarbonyl-
phenyl)porphyrinato]iron(III) chloride 1b (102 mg), ascorbic acid
(0.58 g), and pyridine (10 mL) were added, and the mixture was stirred
at room temperature for 1 h with O2 bubbling. The reaction was
quenched by adding trifluoroacetic acid (6 mL) and 6 M HCl
(100 mL), and the solution was stirred for 30 min. The chloroform
solution was separated and washed with water six times, and the organic
layer was dried over Na2SO4. After the Na2SO4 was filtered off, the
organic layer was evaporated to give a mixture of biladienone, bilindione,
and other pigments. Bilindione was isolated by silica gel column
chromatography eluted with chloroform/acetone (95:5). Biladienone
was obtained in the earlier fraction (40.3 mg, 40.7%). Bilindione eluted
in the later fraction was further purified by silica gel column chroma-
tography using dichloromethane/acetone (9:1). The bilindione fraction
was further purified by preparative silica gel TLC using chloroform, to
yield 14.5 mg (18.5%) of bilindione. 1H NMR (500 MHz, chloroform-d):
δ 0.87 (t, J = 6.25 Hz, 9H, CH3), 1.22ꢀ1.39 (m, 54H, CH2), 1.73 (m,
4H, CH2), 1.80 (m, 2H, CH2), 4.28 (t, J = 6.25 Hz, 4H, CH2), 4.38 (t, J =
6.25 Hz, 2H, CH2), 6.26 (d, J = 5.8 Hz, 2H, pyrrole), 6.46 (d, J = 4.55 Hz,
2H, pyrrole), 6.70 (d, J = 4.55 Hz, 2H, pyrrole), 6.95 (d, J = 5.8 Hz, 2H,
pyrrole), 7.45 (d, J = 8.45 Hz, 4H, phenylene), 7.60 (d, J = 8.40 Hz, 2H,
(4Z,9Z,15Z)-5,10,15-Tri(2-methoxyphenyl)-(21H,23H,24H)-
1,19,21,24-tetrahydro-1,19-bilindione (2e) and (4Z,9Z)-1,-
15,21,24-Tetrahydro-19-(2-methoxybenzoyl)-15-hydroxy-5,-
10,15-tris(2-methoxyphenyl)-23H-bilin-1-one (3e). Chloroform
(500 mL) was placed in a 2-L three-necked flask, and O2 was bubbled
for 60 min. [5,10,15,20-Tetra(2-methoxyphenyl)porphyrinato]iron(III)
chloride 1e (39 mg), ascorbic acid (0.49 g), and pyridine (10.6 mL) were
added, and the mixture was stirred at room temperature for 4 h with O2
bubbling. The reaction was quenched by adding 2 M HCl (500 mL), and
the solution was stirred for 24 h. The chloroform solution was washed with
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The Journal of Organic Chemistry
ARTICLE
water four times, and the organic layer was dried over Na2SO4. After the
Na2SO4 was filtered off, the organic layer was evaporated to give a mixture
of biladienone, bilindione, and other pigments. Bilindione and biladienone
were separated by silica gel column chromatography eluted with chloro-
form. Further purification by silica gel column chromatography using
dichloromethane/acetone (95:5) yielded 5.4 mg (14%) of 3e and 3.3 mg
(10.0%) of 2e.
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Data for 3e. 1H NMR (500 MHz, acetone-d6): δ 3.70ꢀ3.80 (m, 12H,
CH3), 5.85ꢀ5.87 (m, 1H, pyrrole), 6.00 (d, J = 4.55 Hz, 1H, pyrrole),
6.04 (s, 1H; OH), 6.17 (m, 1H; pyrrole), 6.23ꢀ6.26 (m, 1H; pyrrole),
6.42ꢀ6.44 (m, 1H; pyrrole), 6.54ꢀ6.55 (m, 1H; pyrrole), 6.79 (s, 1H;
pyrrole), 6.83 (s, 1H; pyrrole), 6.90ꢀ7.48 (m, 16H; phenyl), 10.2 (s, 1H,
NH), 10.7 (d, J = 31.1 Hz, 1H, NH), 12.9 (s, 1H, NH). 13C NMR (125
MHz, acetone-d6) δ 183.4, 172.2, 138.2, 134.3, 125.8, 124.2, 122.3,
118.7, 111.3, 108.6, 74.6 ppm. MS (TOF): m/z 785 [M + H]+, 767
[M ꢀ OH]+ . HRMS (FAB): calcd for C48H39O6N4 m/z 767.2870,
found 767.2889. UVꢀvis spectrum: λmax (εmax) 326 nm (3.40 ꢁ 104
M
ꢀ1 cmꢀ1), 560 nm (2.29 ꢁ 104 Mꢀ1 cmꢀ1).
1
Data for 2e. H NMR (500 MHz, chloroform-d): δ 3.72 (s, 9H;
CH3), 6.14 (d, J = 5.80, 2H; NH), 6.31 (d, J = 4.50 Hz, 2H; NH), 6.51
(d, J = 3.90 Hz, 2H; NH), 6.83 (d, J = 5.20 Hz, 2H; CH2), 6.92ꢀ7.75
(m, 12H; phenyl). 13C NMR (125 MHz, chloroform-d) δ 171.9, 138.7,
137.8, 130.2, 124.0, 120.6 ppm. MS (TOF): m/z = 648 [M]+. HRMS
(FAB): calcd for C40H32O5N4 m/z 648.2373, found 648.2390. UVꢀvis
spectrum: λmax (εmax) 394 nm (2.69 ꢁ 104 Mꢀ1 cmꢀ1), 613 nm (1.92 ꢁ
104 Mꢀ1 cm ꢀ1).
’ ASSOCIATED CONTENT
Supporting Information. 1H NMR of 2a, 2b, 2c, 2d, and
S
b
2e; 13C NMR of 2a, 2b, 2c, 2d, 2e, and 3e; tables of 13C NMR
chemical shifts of the major signals of 2aꢀf and 3eꢀf; atomic
coordinates of 2a, 2c, 2d, and 2f optimized at the B3LYP/
6-31G(D) level. This material is available free of charge via the
Internet at http://pubs.acs.org.
(14) Asano, N.; Uemura, S.; Kinugawa, T.; Akasaka, H.; Mizutani, T.
J. Org. Chem. 2007, 72, 5320–5326.
’ AUTHOR INFORMATION
(15) Ongayi, O.; Vicente, M. G. H.; Ghosh, B.; Fronczek, F. R.;
Smith, K. M. Tetrahedron 2010, 66, 63–67.
(16) Lente, G.; Fabian, I. Dalton Trans. 2007, 4268–4275.
(17) Kufer, W.; Cmiel, E.; Thuemmler, F.; Ruediger, W.; Schneider,
S.; Scheer, H. Photochem. Photobiol. 1982, 36, 603–7.
Corresponding Author
*Tel: +81-774-65-6623. Fax: +81-774-65-6794. E-mail: tmizutan@
mail.doshisha.ac.jp.
(18) (a) Mizutani, T.; Yagi, S.; Honmaru, A.; Ogoshi, H. J. Am.
Chem. Soc. 1996, 118, 5318–5319. (b) Mizutani, T.; Yagi, S.; Honmaru,
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1998, 63, 8769–8784. (c) Goncharova, I.; Urbanova, M. Anal. Biochem.
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’ ACKNOWLEDGMENT
This work was supported by “Creating Research Center for
Advanced Molecular Biochemistry”, Strategic Development of
Research Infrastructure for Private Universities, the Ministry of
Education, Culture, Sports, Science and Technology (MEXT),
Japan.
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