Substituent effects on selectivity of coupled oxidation of iron tetraphenylporphyrins

Article abstract of DOI:10.1142/S1088424615500455

Coupled oxidation of iron tetraphenylporphyrins bearing either a OMe, Me, F, Cl, COOMe, CF₃ or CN group in the para-position of the phenyl groups gave tetraarylbiladien-ab-1-one and triarylbilindione. The ratios of the yields of the former to those of the latter were linearly correlated with the Hammett substituent constants σ_p⁺, with a positive slope (δσ = 0.64). The Hammett plot of the oxidation rate vs. the substituent constant σ_p also showed a positive slope (σ = 0.30). These substituent effects suggest that a nucleophilic step is included in the formation of bilindione. Coupled oxidation of an A3B type tetraarylporphyrin having an electron withdrawing nitro group in one of the phenyl groups indicated that the oxidation leading to biladienone occurred rather statistically in any of the meso-positions, while the oxidation leading to bilindione occurred preferentially in the meso-position bearing the 4-nitrophenyl group.

Full text of DOI:10.1142/S1088424615500455

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2015; 19: 1–8
DOI: 10.1142/S1088424615500455
Published at http://www.worldscinet.com/jpp/
Substituent effects on selectivity of coupled oxidation
of iron tetraphenylporphyrins
Kazuhisa Kakeya, Atsuko Shimizu, Kenta Akasaka and Tadashi Mizutani*◊
Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, and Center for
Nanoscience Research, Doshisha University, Kyotanabe, Kyoto 610-0321, Japan
Received 14 January 2015
Accepted 5 February 2015
ABSTRACT: Coupled oxidation of iron tetraphenylporphyrins bearing either a OMe, Me, F, Cl,
COOMe, CF3 or CN group in the para-position of the phenyl groups gave tetraarylbiladien-ab-1-one
and triarylbilindione. The ratios of the yields of the former to those of the latter were linearly correlated
with the Hammett substituent constants sp+, with a positive slope (Dr = 0.64). The Hammett plot of the
oxidation rate vs. the substituent constant sp also showed a positive slope (r = 0.30). These substituent
effects suggest that a nucleophilic step is included in the formation of bilindione. Coupled oxidation
of an A3B type tetraarylporphyrin having an electron withdrawing nitro group in one of the phenyl
groups indicated that the oxidation leading to biladienone occurred rather statistically in any of the meso-
positions, while the oxidation leading to bilindione occurred preferentially in the meso-position bearing
the 4-nitrophenyl group.
KEYWORDS: oxidation, porphyrinoids, substituent effects, iron, linear tetrapyrrole.
of a CF3 group on the pyrrole b-position of iron porphyrin
directed the oxidation site to the most electron-rich meso-
position [6].
INTRODUCTION
Oxidative ring opening reactions of porphyrins or
its analogues are important as catabolism of cyclic
tetrapyrroles and biosynthesis of linear tetrapyrroles in
nature. Bilindione [1] (biliverdin) is a linear tetrapyrrole
and biosynthesized from iron porphyrin (heme) by a
reaction catalyzed by heme oxygenase [2]. The red
chlorophyll catabolite is also a linear tetrapyrrole [3].
Oxidation of free base chlorin (pheophorbide a) is
catalysed by pheophorbide a oxygenase [4]. As a model
reaction of biological oxidation of cyclic tetrapyrroles,
coupled oxidation of iron porphyrins with substituents
in the pyrrole b-positions but none in the meso-positions
was studied in detail by Lemberg and others [5].
Compared to the regioselective oxidation by enzymes,
coupled oxidation of unsymmetrically substituted
porphyrins usually occurs non-selectively at meso-
positions. Previously we reported that electronic effects
The oxidation of [tetraarylporphyrinato]iron(III)
chloride carrying phenyl groups at the meso-positions
with molecular dioxygen in the presence of ascorbic acid
and pyridine gave biladien-ab-1-one [7–9] as the major
product and bilindione as a minor one [8,10]. Biladien-
ab-1-one has been obtained by various reactions such
as photochemical oxidation of tetraarylporphyrins,
while meso-arylbilindione was prepared only by the
coupled oxidation [8]. Therefore, it would be desirable
to improve the selectivity of bilindione in the coupled
oxidation.
We previously reported that the lactam and carbonyl
oxygens in biladien-ab-1-one were derived from one
dioxygen molecule, while the two lactam oxygens in
bilindione were derived from two dioxygen molecules
based on the isotope labeling studies using 18O2 [11].
We proposed that a possible key intermediate in
the coupled oxidation of tetraarylporphyrin was the
19-benzoylbilinone iron complex [11]. However, details
of the reaction mechanism and how the electronic effects
SPP full member in good standing
*Correspondence to: Tadashi Mizutani, email: tmizutan@mail.
doshisha.ac.jp, tel: +81 774-65-6623, fax: +81 774-65-6794
Copyright © 2015 World Scientific Publishing Company

2
K. KAKEYA ET AL.
control the bilindione/biladienone selectivity as well
as the meso selectivity for unsymmetrically substituted
tetraarylporphyrins are still unknown.
Therefore the slope of the line shown in Fig. 1 is
Dr, the difference in the reaction constant of bilindione
formation and that of biladienone formation; Dr = 0.64
0.04. The correlation coefficient r2 was 0.968. If a
common intermediate such as a 19-benzoylbilinone
iron complex was assumed, Dr should be interpreted
as the difference in the reaction constants from the
intermediate. When the Hammett substituent constants
sp [13] were used instead of sp+, poorer linear correlation
was observed: r2 = 0.915. We reported that the rate of
bleaching of [tetraphenylporphyrinato]iron under the
coupled oxidation conditions followed the Hammett
equation with a positive reaction constant r = 0.30 [9].
These Hammett studies showed that a nucleophilic
step is included for the formation of bilindione. We
previously proposed that the 19-benzoylbilatrienone iron
complex was formed as an intermediate (Scheme 2).
O2 was activated on the iron and nucleophilic attack of
Fe–O–O- occurs to the acyl group in the 19 position in a
similar fashion to Baeyer–Villiger oxidation to result in
bilindione [11]. In the typical Baeyer–Villiger oxidation
of acetophenones, the Hammett reaction constant was
reported to be negative, indicating that electron-donating
groups accelerated the reaction [14]. The positive sign
of the reaction constant of the coupled oxidation could
imply that the rate-limiting step is nucleophilic attack of
iron-bound oxygen to the carbonyl group.
In this paper, we studied coupled oxidation of a series
of tetraarylporphyrins bearing substituent(s) in the para-
position to clarify electronic effects of the substituents
on the reaction selectivity. We also investigated coupled
oxidation of the iron complex of 5-(4-nitrophenyl)-
10,15,20-triphenylporphyrin. Hammett analysis of the
selectivityofthecoupledoxidationaswellastheselectivity
of coupled oxidation of A3B type tetraarylporphyrins
suggested that an electron withdrawing group in the
phenyl group would facilitate the oxidative cleavage of
the phenyl group to afford bilindione. We demonstrated
that coupled oxidation can be applied to a number of
tetraarylporphyrins bearing various substituents such as
alkoxy, alkyl, ester, cyano, and halogens.
RESULTS AND DISCUSSION
Substituent effects on bilindione/biladienone
selectivity of coupled oxidation
Meso-tetraphenylporphyrins (TPPs) having various
substituents in the para-position were synthesized and
their iron complexes were prepared by refluxing them
with FeCl2 in DMF. Reaction of the iron porphyrins
with dioxygen, ascorbic acid, and pyridine, followed by
work up with hydrochloric acid gave biladien-ab-1-ones
and bilindiones (see Scheme 1). The isolated yields of
biladien-ab-1-ones and bilindiones are listed in Table 1.
Previously we reported that there was a tendency
that the yields of biladien-ab-1-one 2 increased as the
substituents on the aryl groups were electron-donating,
while the yields of bilindiones 3 increased as the
substituents were electron-withdrawing [10]. To analyze
the substituent effects, we plot the ratios of the yields of
bilindione 3 to those of biladien-ab-1-one 2, Yr, against
Coupled oxidation of A3B type porphyrin
We investigated the coupled oxidation of iron
tetraphenylporphyrin bearing a nitro group in one of the
phenylgroups, anA3Btypeporphyrin. 5-(4-Nitrophenyl)-
10,15,20-triphenylporphyrin was synthesized from tetra-
phenylporphyrin and white fuming nitric acid [15].
Coupled oxidation of the iron complex 4 was carried out
and biladien-ab-1-one 5 and bilindione 6 were separated
on silica gel column chromatography (Scheme 3).
The total yields of biladien-ab-1-one 5a–5d and
bilindione 6a–6c were 15.7% and 0.5%, respectively.
1H NMR studies showed that biladien-ab-1-one 5a–5d
were formed statistically, while bilindione 6c was formed
+
Hammett substituent constants sp [12] in Fig. 1. We
found that log Yr was linearly correlated with sp+ and the
slope of the line was 0.64.
When the rate constant of formation of 2, that of
formation of 3, and that of side reactions are assumed
to be k1, k2 and k3, respectively, then the yields of 2 and 3
can be given by:
1
selectively in the reaction. In the H NMR of a mixture
5a–5d, the resonances of the phenyl protons appeared at
7.58, 7.71, 7.75, 7.88, 8.01, 8.23 and 8.30 (overlapped
three signals) ppm. One of the characteristic resonances
of phenyl protons is the benzoyl ortho protons giving the
downfield resonance. The resonance of benzoyl ortho
proton in 19-benzoyl-5,10,15-triphenylbiladien-ab-1-
one was observed at 7.81 ppm [8]. We thus assigned the
resonance at 7.88 ppm to the benzoyl ortho protons of
5a–5c. This resonance had no COSY correlation with any
further downfield resonances, supporting the assignment.
The COSY experiments displayed that the following pairs
of resonances are assigned to vicinal protons: resonances
at7.58ppmand8.23ppm,thoseat7.71ppmand8.30ppm,
those at 7.75 ppm and 8.30 ppm, and those at 8.01 ppm and
k1
k1
1+k2+ k3 )t
[2] =
[3] =
1-[1] e-(k
→
→
(t → ∞)
(t → ∞)
(1)
(2)
(
)
)
0
k1 + k2 + k3
k1 + k2 + k3
k2
k2
1+k2+ k3 )t
1-[1] e-(k
(
0
k1 + k2 + k3
k1 + k2 + k3
If these rate constants follow the Hammett equation:
+
log k1 = r1sp+ and log k2 = r2sp , then Yr is given by:
logYr = logk2 - logk1 = Drs+p where
(3)
(4)
Dr = r -r1.
2
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 2–8

SUBSTITUENT EFFECTS ON SELECTIVITY OF COUPLED OXIDATION OF IRON TETRAPHENYLPORPHYRINS
3
R
R
R
O
O
R
N
Fe
N
1) O2, L-(+)-ascorbic acid,
NH
N
HN
HN
pyridine, in CHCl3
N
N
R
2) 2 M HCl
Cl
OH
R
R
tetraarylporphyrin
iron complex
R
biladien-ab-1-one
1a: R = OCH3
1b: R = CH3
1c: R = H
2a: R = OCH3
2b: R = CH3
2c: R = H
2d: R = F
2e: R = Cl
2f : R = COOCH3
2g: R = CF3
2h: R = CN
1d: R = F
1e: R = Cl
1f : R = COOCH3
1g: R = CF3
1h: R = CN
O
O
NH
HN
R
+
R
N
NH
R
bilindione
3a: R = OCH3
3b: R = CH3
3c: R = H
3d: R = F
3e: R = Cl
3f : R = COOCH3
3g: R = CF3
3h: R = CN
Scheme 1. Coupled oxidation of [tetraarylporphyrinato]iron 1a–h
Table 1. Isolated yields (%) of biladien-ab-1-ones and bilind-
iones of coupled oxidation of tetraarylporphyrins bearing
various substituents
8.30 ppm. The furthest downfield resonances at 8.01 ppm
and 8.30 ppm were assigned to ortho and meta phenyl
protons of 5d, respectively, because of the two electron-
withdrawing groups in a benzene ring. The rest of the
resonances at 7.58, 7.71 and 7.75 ppm and at 8.23, 8.30
and 8.30 ppm were assigned to ortho and meta phenyl
protons, respectively, in 4-nitrobenzoyl group of other
structural isomers 5a–5c. On the basis of the integrals
of the benzoyl protons, the ratio of the yield of 5d to that
of 5a–5c was ca. one to two. Although there is a slight
preference for the cleavage at the meso-position with a
4-nitrophenyl group, we can conclude that the oxidation
resulting in biladienone occurs rather statistically in any
of the meso-positions of 4. To determine which meso
phenyl group was cleaved to give bilindione 6, a TOF-MS
spectrum of a mixture of bilindione 6a–6c was recorded.
Substituent
Biladien-ab-1-one 2
Bilindione 3
p-OCH3 (a)
p-CH3 (b)
H (c)
85a
1.9b
37
1.7
59b
72
4.1b
3.5
p-F (d)
p-Cl (e)
35
2.8
p-COOCH3 (f)
p-CF3 (g)
p-CN (h)
44a
5.9b
32
28a
4.1
6.7b
a Taken from reference 9. b Taken from Ref. 10.
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 3–8

4
K. KAKEYA ET AL.
We previously reported that regioselectivity in
coupled oxidation of porphyrin 7 bearing a CF3 group
in the b-pyrrole position occurred preferentially at
the electronically negative meso-position [6]. To
determine the electron density of the meso carbons of
4, molecular orbital calculations were performed at
the B3LYP/6-31G(D) level. Atomic charges according
to Mulliken population analysis [16] of the meso-
position are listed in Table 2. The atomic charge at
C5 position substituted with 4-nitrophenyl group was
higher than the other meso-positions. The porphyrin
plane and phenyl plane are not planar, and the direct
conjugation of the nitro group with p electron systems
of the porphyrin ring was hindered. The higher electron
density at C5 can be attributed to the through-space
induced dipole moment in the porphyrin p-electrons
by the nitro group. However, electronic polarization
seems much smaller than that of b-CF3 porphyrin 7, in
which the meso Mulliken electron density ranged from
-0.28 to -0.38. Therefore, MO calculations predict that
there are smaller electronic effects on selectivity of
cleavage of 4.
Fig. 1. Hammett plots of the ratios of isolated yields of 3
to those of 2 by coupled oxidation of 1 against Hammett
substituent constants sp+. The reaction constant Dr was 0.64
0.04. sp+ (CN) = 0.71, sp+ (CF3) = 0.53, sp+ (COOMe) = 0.49,
sp+ (Cl) = 0.11, sp+ (H) = 0, sp+ (F) = -0.073, sp+ (Me) = -0.31,
sp+ (OMe) = -0.78
It showed signals at m/z 559 (relative intensity 100) and
at m/z 604 (5). The former signal is attributable to 6c
(MH+), while the latter one to 6a and 6b (MH+), showing
that 6c is the major product. Therefore, the nitrophenyl
group was preferentially cleaved.
The low yield of bilindione (0.5%) is consistent
with a two-step mechanism of bilindione, where the
R
R
O
O
N
N
N
N
N
N
N
N
O2
O2
R
Fe
Fe
R
R
R
ascorbic acid
Cl
R
R
19-benzoylbilatrienone iron complex
R
O
O O
O
O-
NH
NH
HN
N
O
N
HCl
Fe
R
R
R
R
N
N
N
R
R
Scheme 2. Two-step mechanism of bilindione formation
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 4–8

SUBSTITUENT EFFECTS ON SELECTIVITY OF COUPLED OXIDATION OF IRON TETRAPHENYLPORPHYRINS
5
R4
O
O
R3
N
Fe
N
1) O2, L-(+)-ascorbic acid,
pyridine, in CHCl3
NH
N
HN
HN
N
N
R1
2) 2 M HCl
Cl
OH
NO2
4
R2
5a: R1 = NO2, R2, R3, R4 = H
5b: R2 = NO2, R1, R3, R4 = H
5c: R3 = NO2, R1, R2, R4 = H
5d: R4 = NO2, R1, R2, R3 = H
OO
NH
NH
HN
N
R3
R1
+
6a: R1 = NO2, R2, R3 = H
6b: R2 = NO2, R1, R3 = H
6c: R1, R2, R3 = H
R2
Scheme 3. Coupled oxidation of mono-nitro substituted iron tetraphenylporphyrin
Table 2. Atomic charges for [5-(4-nitrophenyl)-10,15,20-
triphenylporphyrinato]iron(II) in the singlet state
EXPERIMENTAL
Commercially available reagents were used as
received. Chromatographic separation of 19-substituted
bilinones was performed using silica gel 60N, spherical
neutral with particle size 40–50 mm, Kanto Chemical
Company. The free base porphyrins were prepared
by refluxing a propionic acid solution of pyrrole and
para-substituted benzaldehyde for 30 min. Mono-nitro
substituted tetraphenylporphyrin was synthesized from
tetraphenylporphyrin and white fuming nitric acid [15].
Iron porphyrins were prepared by refluxing a DMF
solution of porphyrin and iron(II) chloride for 4 h. 1D
NMR and 2D NMR experiments were performed with
a JEOL JNM-ECA500 spectrometer. Tetramethylsilane
Position
Mulliken population analysis
C5 (4-nitrophenyl)
C10 (phenyl)
-0.0598
-0.0563
-0.0 562
-0.0566
C15 (phenyl)
C20 (phenyl)
CF3
Cl
N
N
N
N
1
was used as an internal standard of H and 13C NMR
Fe
1
spectra. H NMR and 13C NMR signals were assigned
using 1H-1H COSY, ROESY, HMBC and HMQC spectra.
UV-visible spectra were recorded on a SHIMADZU
MultiSpec-1500 spectrophotometer and an Agilent 8453
UV-visible spectrophotometer. Matrix-assisted laser
desorption-ionization time-of-flight mass (MALDI-
TOF MS) spectra were recorded on a Bruker Daltonics
Autoflex Speed spectrometer. Fast atom bombardment
mass (FAB MS) spectra were recorded on a JEOL JMS-
700 spectrometer. Preparation and spectroscopic data of
biladien-ab-1-ones 2a, 2c, 2f, 2h and bilindiones 3a, 3c,
3f, 3h were reported elsewhere [8–10].
HO2C
CO2H
7
statistical attack of the meso-positions is followed by
the nucleophilic cleavage of the phenyl group, where
opposite electronic effects are operating.
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 5–8

6
K. KAKEYA ET AL.
(4Z,9Z)-1,15,21,24-tetrahydro-19-(4-methylben-
zoyl)-15-hydroxy-5,10,15-tris(4-methylphenyl)-
23H-bilin-1-one (2b) and (4Z,9Z,15Z)-5,10,15-tris
(4-methylphenyl)-(21H,23H,24H)-1,19,21,24-tetra-
hydro-1,19-bilindione (3b). Chloroform (100 mL) was
placedina500-mLthree-neckedflask,andO2 wasbubbled
for30min. [5,10,15,20-Tetrakis(4-methylphenyl)porphy-
rinato]iron(III) chloride (500 mg, 0.657 mmol), ascorbic
acid (2.3 g, 13 mmol), and pyridine (28 mL, 0.34 mol)
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 (270 mL), and the solution
was stirred for 1 h at room temperature. The chloroform
solution was separated, washed with water twice, and the
organic layer was dried over Na2SO4. After the Na2SO4
was filtered off, the organic layer was evaporated to
give a mixture of biladien-ab-1-one, bilindione and
other pigments. Silica gel column chromatography
eluted with chloroform:acetone (9:1) afforded 178 mg
(37.4%) of 2b as a less polar fraction. Silica gel
column chromatography using chloroform:acetone
(9:1) yielded 6.8 mg (1.7%) of bilindione 3b as
a more polar fraction. 2b. 1H NMR (500 MHz,
chloroform-d): dH, ppm 2.32 (s, 3H, CH3), 2.38 (s, 3H,
CH3), 2.39 (s, 3H, CH3), 2.41 (s, 3H, CH3), 6.13 (d, J =
5.75 Hz, 1H, pyrrole), 6.15–6.18 (m, 2H, pyrrole), 6.33
(d, J = 4.60 Hz, 1H, pyrrole), 6.37 (s, 1H, OH), 6.48 (d,
J = 4.00 Hz, 1H, pyrrole), 6.78–6.80 (m, 2H, pyrrole),
6.87 (d, J = 5.20 Hz, 1H, pyrrole), 7.15 (d, J = 8.00 Hz,
2H, phenylene), 7.20–7.24 (m, 8H, phenylene), 7.37 (d,
J = 8.00 Hz, 2H, phenylene), 7.40 (d, J = 8.00 Hz, 2H,
phenylene), 7.77 (d, J = 8.00 Hz, 2H, phenylene), 10.16
(bs, 1H, NH), 10.87 (bs, 1H, NH), 12.43 (bs, 1H, NH).
13C NMR (125 MHz, chloroform-d): dC, ppm 21.2, 21.3,
21.5, 21.6, 74.9, 109.8, 111.8, 119.5, 121.5, 124.2, 125.4,
125.9, 127.0, 128.6, 128.9, 129.0, 129.2, 129.3, 130.5,
131.0, 131.7, 133.4, 134.4, 134.5, 135.8, 137.8, 138.2,
138.5, 139.2, 139.9, 140.8, 142.2, 142.6, 143.1, 149.6,
150.2, 164.5, 173.3, 184.4. HRMS (FAB): m/z 720.3083
(calcd. for C48H40O3N4 720.3100). UV-vis (CHCl3,
25°C): lmax, nm (emax, M-1.cm-1) 321 (3.03 × 104), 360
(4Z,9Z)-1,15,21,24-tetrahydro-19-(4-fluoroben-
zoyl)-15-hydroxy-5,10,15-tris(4-fluorophenyl)-23H-
bilin-1-one (2d) and (4Z,9Z,15Z)-5,10,15-tris(4-
fluorophenyl)-(21H,23H,24H)-1,19,21,24-tetrahydro-
1,19-bilindione (3d). Coupled oxidation was performed
using [5,10,15,20-tetrakis(4-fluorophenyl)porphyrinato]
iron(III) chloride (500 mg, 0.631 mmol), ascorbic
acid (2.3 g, 13 mmol), and pyridine (27 mL, 0.33
mol), according to the procedures reported above.
Biladien-ab-1-one 2d was isolated by silica gel column
chromatography eluted with chloroform:acetone (95:5),
yielding 346 mg (71.9%) of biladien-ab-1-one 2d. Further
purification by silica gel column chromatography using
chloroform:ethyl acetate (1:1) yielded 14 mg (3.5%) of
1
bilindione 3d. 2d. H NMR (500 MHz, chloroform-d):
dH, ppm 6.15–6.17 (m, 2H, pyrrole), 6.21 (d, J = 5.70 Hz,
1H, pyrrole), 6.31 (d, J = 4.60 Hz, 1H, pyrrole), 6.39 (s,
1H, OH), 6.47 (d, J = 4.00 Hz, 1H, pyrrole), 6.78 (d, J =
4.60 Hz, 1H, pyrrole), 6.81 (d, J = 4.00 Hz, 2.3 Hz, 1H,
pyrrole), 6.87 (d, J = 5.70 Hz, 1H, pyrrole), 7.06 (t, J =
8.60 Hz, 2H, phenylene), 7.13–7.18 (m, 6H, phenylene),
7.34 (dd, J = 8.60 Hz, 5.15 Hz, 2H, phenylene), 7.47
(dd, J = 9.20 Hz, 5.15 Hz, 2H, phenylene), 7.51 (dd, J =
8.60 Hz, 5.15 Hz, 2H, phenylene), 7.91 (dd, J = 8.60 Hz,
5.15 Hz, 2H, phenylene), 9.98 (bs, 1H, NH), 10.88 (bs,
1H, NH), 12.38 (bs, 1H, NH). 13C NMR (125 MHz,
chloroform-d): dC, ppm 74.5, 110.3, 111.95, 115.0,
115.2, 115.4, 119.6, 120.0, 124.7, 125.0, 126.1, 129.0,
129.1, 130.7, 131.47, 131.54, 132.0, 132.3, 137.7, 132.8,
133.2, 133.26, 133.32, 134.5, 134.7, 139.5, 139.7, 141.6,
142.8, 149.8, 149.9, 161.7, 161.8, 162.7, 163.6, 163.7,
164.0, 164.7, 164.9, 166.0, 173.2, 183.1. HRMS (FAB):
m/z 736.2093 (calcd. for C44H28O3N4F4 736.2098).
UV-vis (CHCl3, 25°C): lmax, nm (emax, M-1.cm-1) 350
1
(3.23 × 104), 566 (2.08 × 104). 3d. H NMR (500 MHz,
chloroform-d): dH, ppm 6.26 (d, J = 5.75 Hz, 2H, pyrrole
H-2), 6.49 (d, J = 4.60 Hz, 2H, pyrrole H-7), 6.73 (d, J =
4.60 Hz, 2H, pyrrole H-8), 6.99 (d, J = 5.75 Hz, 2H,
pyrrole H-3), 7.08 (t, J = 8.60 Hz, 4H, 5,15-phenylene
H-2′), 7.20 (t, J = 8.60 Hz, 2H, 10-phenylene H-2′), 7.36
(dd, J = 5.75 Hz, 2.85 Hz, 4H, 5,15-phenylene H-3′), 7.51
(dd, J = 5.75 Hz, 2.85 Hz, 2H, 10-phenylene H-3′), 8.19
(bs, 2H, NH), 12.02 (bs, 1H, NH). 13C NMR (125 MHz,
chloroform-d): dC, ppm 115.23, 115.35, 115.40, 115.53,
117.6, 121.7, 124.3, 130.1, 131.8, 132.6, 133.18, 133.24,
133.31, 137.7, 138.3, 138.7, 139.6, 143.3, 153.4, 162.0,
162.7, 163.9, 164.7, 171.4. MS (MALDI TOF): m/z 613
(calcd. for [M + H]+ 613). HRMS (FAB): m/z 613.1832
(calcd. for C37H24O2N4F3 613.1851). UV-vis (CHCl3,
25°C): lmax, nm (emax, M-1.cm-1) 338 (1.26 × 104), 402
(2.52 × 104), 623 (1.12 × 104).
1
(3.26 × 104), 568 (2.08 × 104). 3b. H NMR (500 MHz,
chloroform-d): dH, ppm 2.32 (s, 6H, CH3), 2.45 (s, 3H,
CH3), 6.22 (d, J = 5.70 Hz, 2H, pyrrole H-2), 6.48 (d, J =
4.60 Hz, 2H, pyrrole H-7), 6.74 (d, J = 4.60 Hz, 2H,
pyrrole H-8), 7.00 (d, J = 5.70 Hz, 2H, pyrrole H-3),
7.16 (d, J = 8.00 Hz, 4H, 5,15-phenylene H-3), 7.25
(overlappedCHCl3, 4H, 5,15-phenyleneH-2′), 7.29(d, J=
7.40 Hz, 2H, 10-phenylene H-3′), 7.41 (d, J = 8.00 Hz,
2H, 10-phenylene H-2′), 8.23 (bs, 2H, NH), 12.05 (bs, 1H,
NH). 13C NMR (125 MHz, chloroform-d): dC, ppm 21.3,
21.4, 119.1, 121.3, 123.8, 128.7, 129.0, 130.0, 131.5,
132.9, 133.9, 137.8, 138.1, 138.4, 139.9, 143.2, 153.4,
171.6. MS (MALDI TOF): m/z 601 (calcd. for [M + H]+
601). HRMS (FAB): m/z 600.2532 (calcd. for C40H32O2N4
(4Z,9Z)-1,15,21,24-tetrahydro-19-(4-chloroben-
zoyl)-15-hydroxy-5,10,15-tris(4-chlorophenyl)-
23H-bilin-1-one (2e) and (4Z,9Z,15Z)-5,10,15-tris
(4-chlorophenyl)-(21H,23H,24H)-1,19,21,24-
tetrahydro-1,19-bilindione (3e). Coupled oxidation was
performed using [5,10,15,20-tetrakis(4-chlorophenyl)
600.2525). UV-vis (CHCl3, 25°C): lmax, nm (emax
,
M-1.cm-1) 351 (1.9 × 104), 408 (3.7 × 104), 623 (1.6 × 104).
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 6–8

SUBSTITUENT EFFECTS ON SELECTIVITY OF COUPLED OXIDATION OF IRON TETRAPHENYLPORPHYRINS
7
porphyrinato]iron(III) chloride (500 mg, 0.594 mmol),
ascorbic acid (2.1 g, 12 mmol), and pyridine (25 mL,
0.33 mol). Biladien-ab-1-one 2e was isolated by silica gel
column chromatography eluted with chloroform:acetone
(95:5), yielding 165 mg (34.9%) of biladien-ab-1-one 2e.
Further purification by silica gel column chromatography
using chloroform:ethyl acetate (1:1)yielded 11 mg (2.8%)
of bilindione 3e. 2e. 1H NMR (500 MHz, chloroform-d):
dH, ppm 6.06 (dd, J = 4.00 Hz, 2.50 Hz, 1H, pyrrole),
6.10 (d, J = 5.75 Hz, 1H, pyrrole), 6.13 (d, J = 4.00 Hz,
1H, pyrrole), 6.27 (d, J = 4.60 Hz, 1H, pyrrole), 6.41 (d,
J = 4.00 Hz, 1H, pyrrole), 6.43 (s, 1H, OH), 6.70 (dd, J =
4.00 Hz, 2.50 Hz, 1H, pyrrole), 6.74 (d, J = 4.60 Hz, 1H,
pyrrole),6.78(d,J=5.75Hz,1H,pyrrole),7.23(d,J=8.60
Hz, 2H, phenylene), 7.27 (d, J = 8.60 Hz, 2H, phenylene),
7.37–7.45 (m, 10H, phenylene), 7.72 (d, J = 8.60 Hz, 2H,
phenylene), 10.65 (bs, 1H, NH), 10.73 (bs, 1H, NH),
12.40 (bs, 1H, NH). 13C NMR (125 MHz, chloroform-d):
dC, ppm 74.4, 110.4, 112.0, 119.65, 119.81, 124.85,
124.99, 126.3, 128.28, 128.56, 128.63, 130.5, 130.7,
131.8, 132.4, 132.7, 134.51, 134.59, 134.72, 134.76,
135.6, 136.0, 136.6, 137.2, 138.1, 139.7, 141.3, 142.1,
142.7, 149.5, 149.8, 164.9, 173.1, 183.3. HRMS (FAB):
m/z 800.0889 (calcd. for C44H28O3N435Cl4 800.0916).
UV-vis (CHCl3, 25°C): lmax, nm (emax, M-1.cm-1) 350
J = 4.00Hz, 1H, pyrrole), 6.54 (s, 1H, OH), 6.71 (dd, J =
4.00 Hz, 2.85 Hz, 1H, pyrrole), 6.73 (d, J = 4.60 Hz,
1H, pyrrole), 6.78 (d, J = 5.75 Hz, 1H, pyrrole), 7.45
(d, J = 8.00 Hz, 2H, phenylene), 7.62 (d, J = 8.60 Hz,
4H, phenylene), 7.67–7.75 (m, 8H, phenylene), 7.85
(d, J = 8.00 Hz, 2H, phenylene), 10.71 (bs, 1H, NH),
10.77 (bs, 1H, NH), 12.53 (bs, 1H, NH). 13C NMR (125
MHz, chloroform-d): dC, ppm 74.6, 110.9, 112.1, 119.7,
122.9, 124.96, 125.03, 125.33, 125.40, 126.0, 126.7,
127.5, 129.4, 130.6, 130.9, 131.0, 130.9, 131.0, 131.52,
131.60, 131.8, 135.1, 137.4, 140.0, 140.3, 140.6, 140.8,
141.3, 142.7, 147.2, 148.9, 150.1, 165.3, 173.2, 183.5.
HRMS (FAB): m/z 936.1963 (calcd. for C48H28O3N4F12
936.1970). UV-vis (CHCl3, 25°C):
lmax, nm
(emax, M-1.cm-1) 344 (3.94 × 104), 565 (2.36 × 104). 3g.
1H NMR (500 MHz, chloroform-d): dH, ppm 6.22 (d, J =
5.70 Hz, 2H, pyrrole H-2), 6.50 (d, J = 4.60 Hz, 2H,
pyrrole H-7), 6.71 (d, J = 4.60 Hz, 2H, pyrrole H-8), 6.96
(d, J = 5.75 Hz, 2H, pyrrole H-3), 7.51 (d, J = 8.00 Hz,
4H, 5,15-phenylene H-2′), 7.65 (d, J = 8.00 Hz, 6H,
5,10,15-phenylene H-3′), 7.77 (d, J = 8.00 Hz, 2H,
10-phenylene H-2′), 8.47 (bs, 2H, NH), 11.94 (bs, 1H,
NH). 13C NMR (125 MHz, chloroform-d): dC, ppm 117.0,
121.9, 122.8, 124.8, 124.9, 125.1, 125.3, 130.1, 130.6,
130.8, 131.6, 131.9, 137.6, 139.1, 139.3, 140.1, 143.1,
153.3, 171.5. MS (MALDI TOF): m/z 763 (calcd. for
[M + H]+ 763). HRMS (FAB): m/z 763.1764 (calcd. for
C40H24O2N4F9 763.1755). UV-vis (CHCl3, 25°C): lmax,nm
(emax, M-1.cm-1) 397 (3.36 × 104), 626 (1.53 × 104).
1
(3.55 × 104), 567 (2.20 × 104). 3e. H NMR (500 MHz,
chloroform-d): dH, ppm 6.27 (d, J = 5.75 Hz, 2H, pyrrole
H-2), 6.50 (d, J = 4.60 Hz, 2H, pyrrole H-7), 6.73 (d, J =
4.60 Hz, 2H, pyrrole H-8), 7.00 (d, J = 5.75 Hz, 2H,
pyrrole H-3), 7.35 (d, J = 8.30 Hz, 4H, 5,15-phenylene),
7.48 (d, J = 8.30 Hz, 4H, 5,15-phenylene), 7.48 (m, 4H,
10-phenylene), 8.28 (bs, 2H, NH), 12.05 (bs, 1H, NH).
13C NMR (125 MHz, chloroform-d): dC, ppm 117.4,
121.7, 124.6, 128.6, 128.8, 130.2, 132.7, 132.9, 134.3,
135.0, 137.8, 138.8, 143.2, 153.2, 171.5. MS (MALDI
TOF): m/z 661 (calcd. for [M + H]+ 661). HRMS (FAB):
660.0863 (calcd. for C37H23O2N435Cl3 m/z 660.0887).
UV-vis (CHCl3, 25°C): lmax, nm (emax, M-1.cm-1) 344
(2.05 × 104), 404 (4.17 × 104), 627 (1.87 × 104).
(4Z,9Z)-1,15,21,24-tetrahydro-19-(4-trifluoro-
methylbenzoyl)-15-hydroxy-5,10,15-tris(4-trifluo-
romethylphenyl)-23H-bilin-1-one (2g) and (4Z, 9Z,
15Z)-5,10,15-tris(4-trifluoromethylphenyl)-
(21H,23H,24H)-1,19,21,24-tetrahydro-1,19-
bilindione (3g). Coupled oxidation was performed
using [5,10,15,20-tetrakis(4-trifluoromethylphenyl)por-
phyrinato]iron(III) chloride (500 mg, 0.512 mmol),
ascorbic acid (2.1 g, 12 mmol), and pyridine (21 mL, 0.27
mol). Biladien-ab-1-one 2g was isolated by silica gel
column chromatography eluted with chloroform:acetone
(95:5), yielding 153 mg (32.0%) of biladien-ab-1-one 2g.
Further purification by silica gel column chromatography
using chloroform:ethyl acetate (1:1) yielded 16 mg(4.1%)
of bilindione 3g. 2g. 1H NMR (500 MHz, chloroform-d):
dH, ppm 6.08 (dd, J = 4.00 Hz, 2.85 Hz, 1H, pyrrole),
6.13 (d, J = 5.75 Hz, 1H, pyrrole), 6.15 (d, J = 4.00 Hz,
1H, pyrrole), 6.25 (d, J = 4.60 Hz, 1H, pyrrole), 6.40 (d,
Coupled oxidation of [5-(4-nitrophenyl)-10,15,20-
triphenylporphyrinato]iron(III) chloride. Chloroform
(100 mL) was placed in a 500-mL three-necked flask,
and O2 was bubbled for 30 min. [5-(4-Nitrophenyl)-
10,15,20-triphenylporphynato]iron(III) chloride (500 mg,
0.667 mmol), ascorbic acid (2.4 g, 14 mmol), and pyridine
(28 mL, 0.35 mol) 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 (270 mL), and
the solution was stirred for 1 h at room temperature. The
chloroform solution was separated, washed with water
twice, and the organic layer was dried over Na2SO4. After
theNa2SO4 wasfilteredoff,theorganiclayerwasevaporated
to give a mixture of biladien-ab-1-one, bilindione and
other pigments. Biladien-ab-1-one and bilindione were
isolated by silica gel column chromatography eluted with
chloroform:acetone (95:5). Further purification by silica gel
column chromatography using chloroform:acetone (98:2)
yielded 74.6 mg (15.7%) of biladien-ab-1-one 5a–5d.
Further purification by silica gel column chromatography
using dichloromethane: acetone (85:15) yielded 1.7 mg
(0.5%) of bilindione 6a–6c.
CONCLUSION
Iron complexes of tetraarylporphyrins having various
substituents in the para-position was oxidized with
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 7–8

8
K. KAKEYA ET AL.
dioxygen in the presence of ascorbic acid and pyridine
to afford biladien-ab-1-one and bilindione. The Hammett
plot of the ratios of yields of the latter to the former
products yielded a straight line with a positive slope. A
nucleophilicstepisincludedintheformationofbilindione.
Oxidation of the tetraphenylporphyrin iron complex with
one nitro group showed that biladien-ab-1-one formed
with the statistical attack at the meso-positions, while
bilindione was formed with the preferential attack at the
meso-position bearing a 4-nitrophenyl group.
Dimsdale MJ. Tetrahedron Lett. 1968; 9: 731–3.
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Acknowledgements
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Chem. Commun. 2005; 1309–1311.
This work was supported by “Creating Research
Centre for Advanced Molecular Biochemistry,” Strategic
Development of Research Infrastructure for Private
Universities, the Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan.
9. Asano N, Uemura S, Kinugawa T, Akasaka H and
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Supporting information
1
Preparation of 2b, 2d, 2e, 2g, 3b, 3d, 3e, and 3g, H
and 13C NMR spectra of 2b, 2d, 2e, 2g, 3b, 3d, 3e, 3g,
5a–5d, and 6a–6c (Scheme S1, Figs S1–S20) is given
in the supplementary material. This material is available
free of charge via the Internet at http://www.worldscinet.
com/jpp/jpp.shtml.
13. McDaniel DH and Brown HC. J. Org. Chem. 1958;
23: 420–427.
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J. Porphyrins Phthalocyanines 2015; 19: 8–8