Synthesis of biladienone and bilatrienone by coupled oxidation of tetraarylporphyrins

Article abstract of DOI:10.1021/jo070692a

(Chemical Equation Presented) Tetraarylbiladien-ab-ones bearing various substituents (R) in the para position of the phenyl groups were preprared by coupled oxidation of tetraarylporphyrin iron complexes. The yields of 5,10,15-triaryl-19-aroyl-15-hydroxyb

Full text of DOI:10.1021/jo070692a

Synthesis of Biladienone and Bilatrienone by Coupled Oxidation of
Tetraarylporphyrins†
Naomi Asano, Sayo Uemura, Tomoya Kinugawa, Hiroaki Akasaka, and Tadashi Mizutani*
Department of Molecular Science and Technology, Faculty of Engineering, Doshisha UniVersity,
Tatara-Miyakotani, Kyotanabe, Kyoto 610-0321, Japan
tmizutan@mail.doshisha.ac.jp
ReceiVed April 6, 2007
Tetraarylbiladien-ab-ones bearing various substituents (R) in the para position of the phenyl groups
were preprared by coupled oxidation of tetraarylporphyrin iron complexes. The yields of 5,10,15-triaryl-
19-aroyl-15-hydroxybiladien-ab-ones were 74% (R ) H), 85% (R ) OMe), 44% (R ) COOMe), and
28% (R ) CN). Kinetic studies of the iron porphyrin oxidation revealed that the reaction is accelerated
by an electron-withdrawing substituent with the Hammett reaction constant F ) 0.295. 5,10,15-Triaryl-
19-aroyl-15-hydroxybiladien-ab-ones undergo the acid-catalyzed elimination reaction either by acetic
acid or by mesoporous silica to afford 5,10,15-triaryl-19-aroylbilatrien-abc-one. The elimination reaction
in acetic acid is accelerated by an electron-donating substituent with the Hammett reaction constant
F ) -1.48.
Introduction
application of these compounds. Introduction of appropriate
substituents to an aromatic core is also an important strategy
for regulation of molecular ordering in crystals or liquid crystals,
which greatly affects its performance as a molecular electronic
device.4 Biladienones were prepared from porphyrin via various
routes including photochemical oxidation,5 chemical oxidation,6
and coupled oxidation.7 Coupled oxidation of iron porphyrins,
oxidation with dioxygen in the presence of a reducing agent
such as ascorbic acid in pyridine, was studied by Lemberg8 in
detail. The reaction is called coupled oxidation because oxidation
Linear tetrapyrroles1 attract interest owing to their extended
π-electron delocalization on a flexible molecular framework,
which leads to unique functions as a scaffold of the supramo-
lecular structures2 as well as molecular electronic materials.3
As electronic materials, tuning of the HOMO and LUMO levels
with appropriate substituents is an attractive strategy, and facile
synthesis of various biladienones should be developed for the
† Dedicated to the memory of Professor Yoshihiko Ito (1937-2006).
* Author to whom correspondence should be addressed. Phone: 81-774-65-
6623. Fax: 81-774-65-6794.
(4) Anthony, J. E.; Brooks, J. S.; Eaton, D. L.; Parkin, S. R. J. Am. Chem.
Soc. 2001, 123, 9482.
(1) Falk, H. The Chemistry of Linear Oligopyrroles and Bile Pigments;
Springer-Verlag: Vienna, New York 1989.
(5) (a) Cavaleiro, J. A. S.; Neves, M. G. P. S.; Hewlins, M. J. E.; Jackson,
A. H. J. Chem. Soc., Perkin Trans. 1 1990, 1937. (b) Cavaleiro, J. A. S.;
Hewlins, M. J. E.; Jackson, A. H.; Neves, M. G. P. M. S. Tetrahedron
Lett. 1992, 33, 6871. (c) Silva, A. M. S.; Neves, M. G. P. M. S.; Martins,
R. R. L.; Cavaleiro, J. A. S.; Boschi, T.; Tagliatesta, P. J. Porphyrins
Phthalocyanines 1998, 2, 45. (d) Jeandon, C.; Krattinger, B.; Ruppert, R.;
Callot, H. J. Inorg. Chem. 2001, 40, 3149. (e) Bonnett, R.; Martinez, G.
Tetrahedron 2001, 57, 9513.
(6) (a) Evans, B.; Smith, K. M.; Cavaleiro, J. A. S. J. Chem. Soc., Perkin
Trans. 1 1978, 768. (b) Ongayi, O.; Vicente, M. G. H.; Ou, Z.; Kadish, K.
M.; Kumar, M. R.; Fronczek, F. R.; Smith, K. M. Inorg. Chem. 2006, 45,
1463.
(2) (a) Mizutani, T.; Yagi, S.; Honmaru, A.; Ogoshi, H. J. Am. Chem.
Soc. 1996, 118, 5318. (b) Mizutani, T.; Yagi, S.; Honmaru, A.; Murakami,
S.; Furusyo, M.; Takagishi, T.; Ogoshi, H. J. Org. Chem. 1998, 63, 8769.
(c) Mizutani, T.; Yagi, S.; Honmaru, A.; Goldacker, T.; Kitagawa, S.;
Furusyo, M.; Takagishi, T.; Ogoshi, H. Supramol. Chem. 1999, 10, 297.
(d) Mizutani, T.; Sakai, N.; Yagi, S.; Takagishi, T.; Kitagawa, S.; Ogoshi,
H. J. Am. Chem. Soc. 2000, 122, 748. (e) Mizutani, T.; Yagi, S. J.
Porphyrins Phthalocyanines 2004, 8, 226. (f) Hamakubo, K.; Yagi, S.;
Hama, S.; Nakazumi, H.; Mizutani, T. Chem. Lett. 2005, 34, 1454.
(3) Matsui, E.; Matsuzawa, N. N.; Harnack, O.; Yamauchi, T.; Hatazawa,
T.; Yasuda, A.; Mizutani, T. AdV. Mater. 2006, 18, 2523.
10.1021/jo070692a CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/09/2007
5320
J. Org. Chem. 2007, 72, 5320-5326

Synthesis of Biladienone and Bilatrienone
SCHEME 1. Coupled Oxidation of Tetraarylporphyrins
of iron porphyrin occurs only if ascorbic acid is concurrently
oxidized. The mechanism of the coupled oxidation has been
studied in relation to the heme oxygenase enzymatic reactions.
Ortiz de Montellano and co-workers reported that heme oxy-
genase oxidized porphyrin derivatives carrying a methyl group
or a formyl group at the meso position.9 For the iron por-
phyrin bearing one methyl group at the meso position, both the
methyl group and the meso carbon were eliminated to yield
bilindione.9a For the iron porphyrin bearing one formyl group
at the meso position, the non-formyl-substituted meso
carbon was selectively eliminated, demonstrating that elec-
tronic effects of the substituent directed the oxidation selec-
tivity.9b Although meso-substituted porphyrins were employ-
ed as a substrate for the enzyme reactions, the substrate of
the coupled oxidation has been limited to the iron complexes
of meso-unsubstituted porphyrins such as protoporphyrin IX
and octaethylporphyrin. Recently, Niemevz et al. reported
that meso-monophenylporphyrin underwent coupled oxida-
tion where the meso-unsubstituted carbon was selectively
oxidized.10
sluggish, and the isolation of the product was laborious. In this
paper, we report our efforts to optimize the reaction conditions
of coupled oxidation to obtain the former product, 5,10,15-
triaryl-19-aroyl-15-hydroxybiladien-ab-ones with various sub-
stituents. We also report that 5,10,15-triaryl-19-aroyl-15-
hydroxybiladien-ab-one undergoes acid-catalyzed thermal
elimination reactions to yield a fully π-conjugated bilatrien-
abc-one.
Results and Discussion
Coupled Oxidation of Tetraarylporphyrins. Coupled oxi-
dation of tetraarylporphyrin proceeds in two steps to yield 5,-
10,15-triaryl- 19-aroyl-15-hydroxybiladien-ab-one and triaryl-
bilindione.11 In the first step, [tetraarylporphyrinato]iron(III)
chloride was treated with pyridine, ascorbic acid, and dioxygen
in chloroform, and then rapid bleaching of the porphyrin Soret
absorption band occurs. In the second step, the resultant reaction
mixture was treated with acid to yield violet pigments, biladi-
enones (Scheme 1). Although several products were obtained
in the reaction, we optimized the reaction conditions to obtain
biladien-ab-one 2 selectively.
We recently reported that the iron complex of tetraphenylpor-
phyrin also underwent coupled oxidation under mild reaction
conditions.11 In the coupled oxidation of the iron complex of
tetraphenylporphyrin, two products with different oxidation
levels were obtained, 15-hydroxybiladien-ab-one where the
meso carbon was retained as the benzoyl carbonyl carbon, and
bilindione where a meso carbon and a phenyl group were
eliminated. The reaction affording the latter product was
Figure 1 shows the UV-visible spectral changes of a solu-
tion of [5,10,15,20-tetraphenylporphyrinato]iron(III) chloride,
(7) (a) Bonnett, R.; Dimsdale, M. J. Tetrahedron Lett. 1968, 9, 731. (b)
Bonnett, R.; Dimsdale, M. J. J. Chem. Soc., Perkin Trans. 1 1972, 2540.
(c) Bonnett, R.; McDonagh, A. F. J. Chem. Soc., Perkin Trans. 1 1973,
881. (d) Balch, A. L.; Latos-Grazynski, L.; Noll, B. C.; Olmstead, M. M.;
Szterenberg, L.; Safari, N. J. Am. Chem. Soc. 1993, 115, 1422. (e) Balch,
A. L.; Latos-Grazynski, L.; Noll, B. C.; Olmstead, M. M.; Safari, N. J.
Am. Chem. Soc. 1993, 115, 9056. (f) Morishima, I.; Fujii, H.; Shiro, Y.;
Sano, S. Inorg. Chem. 1995, 34, 1528. (g) Johnson, J. A.; Olmstead, M.
M.; Balch, A. L. Inorg. Chem. 1999, 38, 5379.
(8) (a) Lemberg, R. Biochem. J. 1935, 29, 1322. (b) Lemberg, R.; Cortis-
Jones, B.; Norrie, M. Biochem. J. 1938, 32, 149.
(9) (a) Torpey, J.; Ortiz, de Montellano, P. R. J. Biol. Chem. 1996, 271,
26067. (b) Torpey, J.; Ortiz, de Montellano, P. R. J. Biol. Chem. 1997,
272, 22008.
(10) (a) Niemevz, F.; Alvarez, D. E.; Buldain, G. Y. Heterocycles 2002,
57, 697. (b) Niemevz, F.; Buldain, G. Y. J. Porphyrins Phthalocyanines
2004, 8, 989.
(11) Yamauchi, T.; Mizutani, T.; Wada, K.; Horii, S.; Furukawa, H.;
Masaoka, S.; Chang, H.-C.; Kitagawa, S. Chem. Commun. 2005,
1309.
FIGURE 1. UV-visible spectral changes of 1.5 × 10-5 M of [5,10,-
15,20-tetraphenylporphyrinato]iron(II), 1.32 M of pyridine, and 5.7 ×
10-3 M of ascorbic acid in dioxygen-saturated chloroform at 25 °C.
Spectra were recorded every 1 min, and the half-life was estimated to
be 6 min.
J. Org. Chem, Vol. 72, No. 14, 2007 5321

Asano et al.
FIGURE 2. Plot of the rate constant of the Soret band bleaching of
1a against pyridine concentration. For the reaction conditions, see the
legend to Figure 1.
FIGURE 3. Plot of the coupled oxidation rate constant against
Hammett substituent constant σ. The slope gave the reaction constant
F 0.295.
TABLE 1. Rate Constants (kox) of Coupled Oxidation of Iron
Porphyrins (298 K, CHCl3)a
ferric 2,4-diacetyldeuteroporphyrin are selectively attacked in
the coupled oxidation.14 These studies revealed that higher
π-electron denisity is favorable for the porphyrin oxidation. If
this effect is dominant, we expect that electron-donating
substituent in the porphyrin phenyl groups will accelerate the
coupled oxidation reaction. Another factor is activation of the
coordinated dioxygen by electron-withdrawing substituents. In
cytochrome P-450 model reactions, oxidation of cyclohexane
with iron porphyrins carrying electron-withdrawing subsituents
in the phenyl groups proceeds faster than those with electron-
donating substituents.15 The Hammett reaction constant was in
the range of 0.3-0.5. Although the intermediate of the P-450
model reaction is different from that of the coupled oxidation,
similar activation by electron-withdrawing groups is expected
for coupled oxidation. The overall reaction rate will be
determined by the balance of these two factors, and the latter
factor seems to be dominant in the present reactions.
When bleached solutions were treated with acid, the color
of the solution turned violet to yield 15-hydroxybiladien-ab-
one. Previously we used NaBF4 to precipitate the product
followed by the acid treatment, but direct treatment of a
chloroform solution with 1 M aqueous HCl in a two-phase
system is a simple and better procedure to avoid further
decomposition of 15-hydroxybiladien-ab-one. We reported the
longer reaction period for the coupled oxidation of 1d, but we
found that a longer reaction period induced decomposition of
the product. The yields of 2a, 2b, 2c, and 2d were 74, 85, 44,
and 28%, respectively. With the reported procedure, the isolated
yield of biladien-ab-one bearing electron-withdrawing substit-
uents were lower.11 This is true for the modified procedure
reported here. The lower yield of cyanophenyl biladienone 2d
was attributed to the higher reactivity of the porphyrin 1d toward
oxidation. It seems to be more difficult to find out the optimum
reaction conditions for the highly reactive iron porphyrin having
electron-withdrawing groups.16
substituent
kox/min-1
σp
1a
1b
1c
1d
H
0.175 ( 0.014
0.163 ( 0.017
0.220 ( 0.022
0.302 ( 0.020
0
OMe
COOMe
CN
-0.27
0.31
0.66
a Each rate constant is the average of 3-4 independent determinations.
ascorbic acid, and pyridine in dioxygen-saturated chloro-
form. The rate of bleaching was first order in the porphyrin
concentration.
d[1]
dt
-
) kox
(1)
The first-order rate constant kox was determined by following
the absorbance changes over one half-life. The rate constants
are plotted against the concentration of pyridine in Figure 2.
The rate was accelerated by adding pyridine and showed
saturation at a high concentration of pyridine (1.3 M).8a,12 Using
1.3 M of pyridine, several tetraarylporphyrins 1a-d were
subjected to the coupled oxidation. The rate constants of the
Soret band bleaching kox were determined at 298 K for four
iron porphyrins 1a-d bearing either electron-donating or
electron-withdrawing groups and are listed in Table 1. The
Hammett plot is shown in Figure 3. Electron-withdrawing
substituents accelerated bleaching, and the slope of the line gave
the Hammett reaction constant F of 0.295.
For electronic effects on porphyrin oxidation, Torpey and
Ortiz de Montellano demonstrated that the oxidation of heme
by heme oxygenase occurs via electrophilic attack of oxygen
to the meso carbon.9 We previously reported that coupled
oxidation of 18-trifluoromethylporphyrin occurs at the meso-
carbon with the highest electron density, C-5, consistent with
the mechanism of electrophilic attack of oxygen to the meso
carbon.13 Zhu and Silvermann recently reported that the por-
phyrin meso positions that are at higher π-electron densities in
Dehydration of 15-Hydroxybiladien-ab-one. The UV-
visible spectral changes in a solution of 15-hydroxybiladien-
ab-ones 2a-d in acetic acid heated at 45 °C are shown in Figure
(12) For the role of pyridine in the coupled oxidation process of meso-
unsubstituted porphyrins, see ref. 8a and Balch, A. L.; Koerner, R.; Latos-
Grazynski, L.; Lewis, J. E.; St. Claire, T. N.; Zovinka, E. P. Inorg. Chem.
1997, 36, 3892.
(13) Crusats, J.; Suzuki, A.; Mizutani, T.; Ogoshi, H. J. Org. Chem. 1998,
63, 602.
(14) Zhu, Y.; Silverman, R. B. Org. Lett. 2007, 9, 1195.
(15) Guo, C.-C.; Song, J.-X.; Chen, X.-B.; Jiang, G.-F. J. Mol. Catal. A
2000, 157, 31.
(16) For the oxidation of bile pigments, see Eivazi, F.; Hudson, M. F.;
Smith, K. M. Tetrahedron Lett. 1976, 3837.
5322 J. Org. Chem., Vol. 72, No. 14, 2007

Synthesis of Biladienone and Bilatrienone
FIGURE 4. UV-visible spectral change of 2a (a), 2b (b), 2c (c), and 2d (d) (5 × 10-6 M) in acetic acid upon heating (318 K). Spectra were
recorded every 1 min (a), 0.5 min (b), 2 min (c), and 10 min (d).
4. For 2a, the absorbance at 589 nm decreased with concomitant
increase in absorbance at 442 and 718 nm. These spectral
changes are similar to those observed when the zinc complex
of 15-hydroxybiladien-ab-one was heated in chloroform to
produce the dehydrated bilatrien-abc-one zinc complex.5b
Evaporation of the acetic acid and the residue was analyzed by
1H NMR. The 1H NMR spectrum was consistent with the
dehydrated bilatrien-abc-one structure 3a.17 Attempt to
isolate pure 3a was not successful since partial decomposi-
tion of 3a occurs during evaporation of the acetic acid. We
found that by using mesoporous silica FSM-16,18 a solid acid,
instead of acetic acid isolation of the product is easier.
Thus a solution of biladien-ab-one 2a in benzene was refluxed
for 3 h over FSM-16, followed by filtration to remove the
catalyst. Evaporation of the benzene gave almost pure 3a.Ap-
parently FSM-16 acts as a solid acid and a dehydrating agent.
Silica gel can also be used as a catalyst, showing similar catalytic
activity.
material 2a disappeared and new signals appeared at 171 and
189 ppm. Since the major and minor isomers showed different
1H NMR chemical shifts, complete assignment of signals of
1
both isomers were not performed. Instead, the H NMR of the
major isomer of (4Z,9Z,14Z)-1,21-dihydro-19-(4-undecyloxy-
benzoyl)-5,10,15-tris(4-undecyloxyphenyl)-23H-bilin-1-one (3e)19
1
was assigned by H-1H COSY, ROESY, and HMBC spectra
since 1H NMR signals of 3e were better resolved. The HMBC
spectrum indicated that there are correlations between C1 and
H2/H3, C20 and the ortho proton of the p-alkoxybenzoyl group,
C19 and H18/H17, and C6 and H7/H8. ROESY correlations
were observed between H3 and the ortho protons of the 5-phenyl
group, H12 and the ortho protons of the 10-phenyl group, and
H17 and the ortho protons of the 15-phenyl group. COSY
correlations between NH protons and H2/H3 and H12/H13
(19) Kita, K.; Tokuoka, T.; Monno, E.; Yagi, S.; Nakazumi, H.; Mizutani,
T. Tetrahedron Lett. 2006, 47, 1533.
(20) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; J. A. Montgomery, J.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.; Gaussian, Inc.,
Pittsburgh, PA, 2003.
1H NMR of 3a showed that the three NH signals at 10.0,
10.8, and 12.5 ppm of 2a disappeared and two sets of NH
protons appeared at 10.3 and 13.1 ppm (major isomer) and 11.1
and 13.2 ppm (minor isomer), suggesting that two isomers are
formed and are in equilibrium. The molar ratio of the major
isomer to the minor isomer was ca. 4:1. 13C NMR showed that
the signals at 77 (C-15), 173 (C-1), and 184.7 (C-20, the
carbonyl carbon of the 19-benzoyl group) ppm of the starting
(17) (a) Smith, K. M.; B.; B. S.; Troxler, R. F.; Lai, J.-J. Tetrahedron
Lett. 1980, 21, 2763. (b) Matsuura, T.; Inoue, K.; Ranade, A. C.; Saito, I.
Photochem. Photobiol. 1980, 31, 23.
(18) Inagaki, S.; Fukushima, Y.; Kuroda, K. J. Chem. Soc., Chem.
Commun. 1993, 680.
J. Org. Chem, Vol. 72, No. 14, 2007 5323

Asano et al.
SCHEME 2. Acid-Catalyzed Dehydration of Biladien-ab-one 2 To Afford Bilatrien-abc-one 3
established that the major isomer has protons at N21 and N23.
Characteristic feature of the 1H NMR is that the ortho
protons of the 5-phenyl group is shifted upfield. This upfield
shift is consistent with the 19-antiperiplanar conformer where
the ortho proton of the 5-phenyl group is close to the 20-phenyl
group. These spectral features are consistent with the formation
of bilatrienone 3e. For bilatrien-abc-one, there are several
isomers as shown in Scheme 2, such as the positional isomers
of the protonated nitrogens and the synperiplanar/antiperi-
planar (sp/ap) isomers of the C19-C20 bond. B3LYP/6-31G*
calculations indicate that the 19,ap-21,23H isomer is the most
stable (Figure 5). On the basis of NMR studies, the major isomer
was assigned to 19,ap-21,23H-3e. The structure of the minor
isomer was not determined: a similar 1H NMR pattern suggests
that the minor isomer has similar structure to that of the major
isomer.
and the rate constants kel of the elimination reaction were
determined.
d[2]
dt
-
) kel
(2)
The first-order rate constants kel are listed in Table 2. For 2a
and 2b, UV-visible spectral changes showed isosbestic points
while for 2c and 2d, no isosbestic points were observed. The
absence of isosbestic points may be due to the formation of
isomers as shown in Scheme 2. Plot of log kel against σ gave
the slope of -1.48 as a Hammett reaction constant (Figure 6).
The dehydration is accelerated by electron-donating substituents,
and the E1 mechanism where a carbenium ion is an intermediate
is proposed. The dihedral angle of the 15-phenyl group and the
dipyrromethene in 3a was 52.8° according to the molecular
orbital calculations (B3LYP/6-31G*). Therefore we suggest that
π-electron conjugation between the carbenium ion at C-15 and
The UV-visible spectral changes due to the conversion
of 2 to 3 were analyzed based on the first-order kinetics,
FIGURE 5. Relative energy of four isomers of bilatrien-abc-one 3a geometry optimized by molecular orbital calculations at the B3LYP/6-31G*
level.20
5324 J. Org. Chem., Vol. 72, No. 14, 2007

Synthesis of Biladienone and Bilatrienone
TABLE 2. Rate Constants of Dehydration of
were added pyrrole (11.2 mL, 0.16 mol) and p-methoxybenzalde-
hyde (19.4 mL, 0.16 mol), and the solution was refluxed for 30
min in dark. After the reaction mixture was cooled to room
temperature, crystals were collected by suction-filtration and washed
with methanol. The crystals were dissolved in chloroform and
reprecipitated with an excess amount of methanol to afford 5.15 g
(17.5%) of violet crystals. 1H NMR (500 MHz, CDCl3) δ 8.86 (s,
8H), 8.12 (d, 8H), 7.28 (d, 8H), 4.10 (s, 12H), -2.75 (s, 2H), FAB-
MS m/z 734 (M+).
15-Hydroxybiladien-ab-ones (298 K, acetic acid)
substituent
kel/min-1
σp
2a
2b
2c
2d
H
(9.44 ( 0.70) × 10-2
(1.58 ( 0.03) × 10-1
(2.37 ( 0.23) × 10-2
(7.48 ( 0.11) × 10-3
0
OMe
COOMe
CN
-0.27
0.31
0.66
[5,10,15,20-Tetrakis(4-methoxyphenyl)porphyrinato]iron-
(III) Chloride (1b). TPP-OMe 2.51 g (3.42 mmol) was placed in
a 500-mL three-necked flask, DMF (50 mL) was added, and the
solution was refluxed. FeCl2‚4H2O (21.8 g, 0.11 mol) in 200 mL
of DMF was then added, and the solution was refluxed for 3 h.
After the mixture was cooled to room temperature, 600 mL of
CHCl3 was added. The organic layer was washed three times with
1 M HCl and twice with water. The organic layer was dried over
anhydrous sodium sulfate and evaporated to afford 2.81 g (99.8%)
of dark violet crystals. FAB-MS m/z 788 (M - Cl-).
(4Z,9Z)-1,15,21,24-Tetrahydro-19-(4-methoxybenzoyl)-15-hy-
droxy-5,10,15-tris(4-methoxy-phenyl)-23H-bilin-1-one (ZZ) (2b).
[5,10,15,20-Tetrakis(4-methoxyphenyl)porphyrinato]iron(III) chlo-
ride (38.1 mg, 0.0484 mmol) was placed in a 100-mL flask, and 6
mL of pyridine was added. A 50 mL amount of dioxygen-saturated
CHCl3 was added, followed by 0.51 g of L-ascorbic acid. The
solution was stirred at room temparature for 1 h with dioxygen
bubbling. The reaction mixture was diluted with CHCl3 (50 mL),
and 1 M HCl (150 mL) was added. The solution was stirred at
room temperature for 1 h. The CHCl3 layer was separated and
washed with water twice. The organic layer was dried over
anhydrous sodium sulfate, and the solvent was evaporated in vacuo.
The residue was chromatographed on silica (CH2Cl2:acetone ) 96:
4) to afford 32 mg (84.7%) of violet crystals. 1H NMR (500 MHz,
CDCl3) δ 3.80 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H), 3.89 (s, 3H),
6.18 (m, 3H, H-2, 13, 17), 6.38 (d, 1H, H-7), 6.32 (s, 1H, OH),
6.52 (1H, d, H-12), 6.82 (m, 2H, H-8, 18), 6.89 (d, 2H, meta-H of
15-phenyl), 6.90 (d, 1H, H-3), 6.95 (d, 2H, meta-H of 20-phenyl),
6.96 (d, 2H, meta-H of 5-phenyl), 6.98 (d, 2H, meta-H of
10-phenyl), 7.29 (d, 2H, ortho-H of 5-phenyl), 7.39 (d, 2H, ortho-H
of 15-phenyl), 7.49 (d, 2H, ortho-H of 10-phenyl), 7.91 (d, 2H,
ortho-H of 20-phenyl), 9.90 (s, 1H, 24N-H), 11.0 (s, 1H, 21N-H),
12.3 (s, 1H, 23N-H). FAB-MS (3-nitrobenzyl alcohol) m/z ) 767
(M - OH+), 784 (M+).
FIGURE 6. Plot of the dehydration rate constant kel against the
Hammett substituent constant. The slope gave the reaction constant F
-1.48. Each rate constant is the average of three to five independent
determinations.
the p-OMe occurs only partially. Therefore, use of σ instead of
σ+ would be more appropriate. Linear correlation was indeed
obtained using σ.
In conclusion, 15-hydroxybiladien-ab-ones and bilatrien-abc-
ones with various substituents were prepared by coupled
oxidation and the subsequent acid-catalyzed elimination reaction,
respectively. Electronic effects of substituents were analyzed
by the Hammett equation. Coupled oxidation of the iron
tetraarylporphyrin was accelerated by electron-withdrawing
substituents while elimination of 15-hydroxybiladien-ab-one to
bilatrien-abc-one was accelerated by electron-donating substit-
uents. The lower isolated yield of the 15-hydroxybiladien-ab-
one bearing electron-withdrawing substituents was attributed to
the higher reactivity of the porphyrin, for which optimization
of the reaction conditions was more difficult.
5,10,15,20-Tetrakis(4-methoxycarbonylphenyl)porphyrin (TPP-
COOMe). To refluxed propionic acid (150 mL) in a 500-mL three-
necked flask were added pyrrole (2.8 mL, 0.04 mol) and methyl
p-formylbenzoate (6.57 g, 0.04 mol), and the solution was refluxed
for 30 min in dark. After the reaction mixture was cooled to room
temperature, crystals were collected by suction-filtration to afford
Experimental Section
1
1.25 g (14.8%) of violet crystals. H NMR (500 MHz, CDCl3) δ
(4Z,9Z)-1,15,21,24-Tetrahydro-19-benzoyl-15-hydroxy-5,10,-
15-triphenyl-23H-bilin-1-one (2a). [5,10,15,20-tetraphenylpor-
phyrinato]iron(III) chloride (38 mg, 0.055 mmol) was placed in a
100-mL flask, and 6 mL of pyridine was added. A 50 mL amount
of dioxygen-saturated CHCl3 was added, followed by 0.51 g (2.85
mmol) of ascorbic acid. The solution was stirred at room tempara-
ture with dioxygen bubbling. The reaction mixture was diluted with
CHCl3 (50 mL), and 1 M HCl (150 mL) was added. The solution
was stirred at room temperature for 1 h. The CHCl3 layer was
separated and washed with water twice. The organic layer was dried
over anhydrous sodium sulfate, and the solvent was evaporated in
vacuo. The residue was chromatographed on silica (CH2Cl2:acetone
8.82 (s, 8H), 8.44 (d, 8H), 8.3 (d, 8H), 4.11 (s, 12H), -2.82 (s,
2H), FAB-MS m/z 846 (M+).
[5,10,15,20-Tetrakis(4-methoxycarbonylphenyl)porphyrinato]-
iron(III) Chloride (1c). A solution of TPP-COOMe 0.504 g (0.59
mmol) and FeCl2‚4H2O (2.3 g, 11.8 mmol) in 50 mL of DMF was
refluxed for 4 h. After the mixture was cooled to room temperature,
300 mL of CHCl3 was added. The organic layer was washed three
times with 1 M HCl and twice with water. The organic layer was
dried over anhydrous sodium sulfate and evaporated to afford 0.485
g (91.2%) of dark violet crystals. FAB-MS m/z 900 (M - Cl-).
(4Z,9Z)-1,15,21,24-Tetrahydro-19-(4-methoxycarbonylbenzoyl)-
15-hydroxy-5,1 0,15-tris(4-methoxycarbonylphenyl)-23H-bilin-
1-one (COOMeBD, 2c). [5,10,15,20-Tetrakis(4-methoxycarbon-
ylphenyl)porphyrinato]iron(III) chloride 38.5 mg (42.8 mmol) was
placed in a 100-mL flask, and 6 mL of pyridine was added. 50 mL
of dioxygen-saturated CHCl3 was added, followed by 0.5 g of
L-ascorbic acid. The solution was stirred at room temparature for
1 h with dioxygen bubbling. To the reaction mixture was added
150 mL of 1 M aqueous HCl. The mixture was stirred for 3 h at
1
) 96:4) to afford a violet crystal (28 mg, 73.7%). H NMR (500
MHz, CDCl3) δ 6.18 (m, 3H, H-2, 13, 17), 6.32 (d, 1H, H-7), 6.36
(s, 1H, OH), 6.49 (1H, d, H-12), 6.78 (d, 1H, H-8), 6.82 (dd, 1H,
H-18), 6.89 (d, 1H, H-3), 7.88 (d, 2H, ortho-H of 20-phenyl), 9.95
(1H, s, 23N-H), 10.8 (1H, s, 21N-H), 12.5 (1H, s, 24N-H). FAB-
MS (3-nitrobenzyl alcohol) m/z ) 647 (M - OH+), 664 (M+).
5,10,15,20-Tetrakis(4-methoxyphenyl)porphyrin (TPP-OMe).
To refluxed propionic acid (600 mL) in a a 1-L three-necked flask
J. Org. Chem, Vol. 72, No. 14, 2007 5325

Asano et al.
room temperature. The organic layer was separated, washed with
water twice, dried over anhydrous sodium sulfate, and evaporated.
The residue was chromatographed on silica gel column (CHCl3:
acetone, 96:4) to obtain 17 mg (44.4%) of violet crystals. 1H NMR
(500 MHz, CDCl3) δ 3.91 (s, 3H), 3.95 (s, 3H), 3.96 (s, 3H), 3.97
(s, 3H), 6.17 (m, 2H, H-12, 17), 6.23 (d, 1H, H-2), 6.47 (s, 1H,
OH), 6.27 (1H, d, H-7), 6.43 (d, 1H, H-13), 6.74 (1, 2H, H-8),
6.80 (dd, 1H, H-18), 6.85 (d, 1H, H-3), 7.44 (d, 2H, ortho-H of
5-phenyl), 7.59 (d, 4H, ortho-H of 10,15-phenyl), 7.90 (d, 2H,
ortho-H of 20-phenyl), 8.10 (m, 8H, meta-H of 5,10,15-phenyl),
10.0 (s, 1H, 24N-H), 10.8 (s, 1H, 21N-H), 12.5 (s, 1H, 23N-H).
FAB-MS (3-nitrobenzyl alcohol) m/z ) 879 (M - OH+), 896 (M+).
5,10,15,20-Tetrakis(4-cyanophenyl)porphyrin (TPP-CN). To
refluxed propionic acid (60 mL) in a 100-mL three-necked flask
were added pyrrole (1.12 mL, 0.016 mol) and p-cyanobenzaldehyde
(2.1 g, 16 mmol), and the solution was refluxed for 30 min in the
dark. After the reaction mixture was cooled to room temperature,
crystals were collected by suction-filtration and washed with
methanol. The crystal was dissolved in dichloromethane and
chromatographed on silica gel (CH2Cl2) to afford 0.15 g (5.3%) of
stirred at room temparature for 1 h with dioxygen bubbling. The
reaction mixture was transferred to 300 mL beaker, 50 mL of 1 M
aqueous HCl was added, and the mixture was stirred at room
temperature for 3 h. The organic layer was separated, washed with
water twice, dried over anhydrous sodium sulfate, and evaporated.
The residue was chromatographed on silica gel column (CHCl3:
acetone, 96:4) to obtain 5 mg (28.0%) of violet crystals. 1H NMR
(500 MHz, CDCl3) δ 6.16 (dd, 1H, H-17), 6.26 (d, 1H, H-2), 6.28
(d, 1H, H-7), 6.40 (1H, d, H-12), 6.52 (s, 1H, OH), 6.72 (d, 1H,
H-8), 6.79 (dd, 1H, H-18), 6.85 (d, 1H, H-3), 7.49 (d, 2H, ortho-H
of 5-phenyl), 7.63 (d, 2H, ortho-H of 10-phenyl), 7.64 (d, 2H,
ortho-H of 15-phenyl), 7.69 (d, 2H, meta-H of 15-phenyl), 7.78
(m, 4H, meta-H of 5- and 20-phenyl), 7.79 (d, 2H, meta-H of 10-
phenyl), 7.94 (d, 2H, ortho-H of 20-phenyl), 10.1 (s, 1H, 24N-H),
10.8 (s, 1H, 21N-H), 12.4 (s, 1H, 23N-H). 13C NMR (CDCl3) δ
183 (C-1), 173 (C-20), 74 (C-15). FAB-MS (3-nitrobenzyl alcohol)
m/z ) 747 (M - OH+), 764 (M+).
(4Z,9Z,14Z)-1,21-Dihydro-19-(4-undecyloxybenzoyl)-5,10,15-
tris(4-undecyloxyphenyl)-23H-bilin-1-one (3e). The major isomer
was assigned by 1H-1H COSY, ROESY, and HMBC spectra: 1H
NMR (500 MHz, CDCl3) δ 0.88 (t, 12H), 1.26-1.49 (m, 72H),
1.73-1.89 (m, 8H), 3.96-4.09 (m, 8H), 6.05 (d, 1H, H-2), 6.45
(d, 1H, H-17), 6.50 (d, 2H, H-3′ of 20-aryl), 6.72 (d, 1H, H-13),
6.74 (d, 1H, H-3), 6.79 (d, 1H, H-12), 6.87 (d, 2H, H-2′ of 5-aryl),
6.95-6.99 (m, 5H, H-18, H-3′ of 5-aryl, H-3′ of 15-aryl), 6.99-
7.03 (m, 3H, H-8, H-3′ of 10-aryl), 7.13 (d, 1H, H-7), 7.50 (d, 2H,
H-2′ of 15-aryl), 7.59 (d, 2H, H-2′ of 10-aryl), 8.18 (d, 2H, H-2′
of 20-aryl), 10.08 (br s, 1H, N21-H), 13.05 (br s, 1H, N23-H).
1
violet crystals. H NMR (500 MHz, CDCl3) δ 8.79 (s, 8H), 8.33
(d, 8H), 8.10 (d, 8H), -2.89 (s, 2H), FAB-MS m/z 715 (M+H+).
[5,10,15,20-Tetrakis(4-cyanophenyl)porphyrinato]iron(III)
Chloride (FeCl(TPP-CN), 1d). TPP-CN 103 mg (0.144 mmol)
was placed in a 200-mL three-necked flask, and DMF (50 mL)
was added and refluxed. FeCl2‚4H2O (0.836 g, 4.2 mmol) in 50
mL of DMF was then added, and the solution was refluxed for 7
h. After the mixture was cooled to room temperature, 200 mL of
CH2Cl2 was added. The organic layer was washed three times with
300 mL of 1 M HCl and twice with water. The organic layer was
dried over anhydrous sodium sulfate and evaporated to afford 0.104
g (89.7%) of dark violet crystals. FAB-MS m/z 768 (M - Cl-).
(4Z,9Z)-1,15,21,24-Tetrahydro-19-(4-cyanobenzoyl)-15-hydroxy-
5,10,15-tris(4-cyanophenyl)-23H-bilin-1-one (2d). [5,10,15,20-
Tetrakis(4-cyanophenyl)porphyrinato]iron(III) chloride (1d) (18 mg,
0.0234 mmol) was placed in a 100-mL flask, and 3 mL of pyridine
was added. A 25 mL amount of dioxygen-saturated CHCl3 was
added, followed by 0.25 g of L-ascorbic acid. The solution was
Supporting Information Available: 1H NMR spectra and 13
C
NMR spectra of 2a, 2b, 2c, 2d, and 3e. 2D COSY, ROESY/
NOESY, and HMBC analysis of 2c, 2d, and 3e. B3LYP/6-31G*-
optimized geometries and Cartesian coordinates and total energy
of 19,ap-21,23H-3, 19,sp-21,23H-3, 19,sp-22,24H-3, 19,ap-22,-
24H-3. This material is available free of charge via the Internet at
http://pubs.acs.org.
JO070692A
5326 J. Org. Chem., Vol. 72, No. 14, 2007