Oligocyclization of 2-(hydroxymethyl)pyrroles with electron-withdrawing groups at β-positions: Formation and structural elucidation of porphyrinogens and hexaphyrinogens

Article abstract of DOI:10.1039/b307132d

Acid-catalyzed oligomerization of 2-(hydroxymethyl)pyrroles bearing C₆F₅, 2,6-Cl₂C₆H₃, CF₃ and CO₂Et groups at β-positions was examined. The reaction of ethyl pyrrole-3-carboxylates gave a mixture of oligomers and type I isomers of porphyrinogens and hexaphyrinogens were isolated when the other β-substituents were sufficiently bulky, for example, mesityl, 2,6-Cl₂C₆H₃ and C₆F₅ groups. On the other hand, the pyrroles having other electron-withdrawing groups afforded porphyrinogens as the only isolable products.

Full text of DOI:10.1039/b307132d

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Oligocyclization of 2-(hydroxymethyl)pyrroles with electron-
withdrawing groups at ꢀ-positions: formation and structural
elucidation of porphyrinogens and hexaphyrinogens†
Hidemitsu Uno,*a Kentarou Inoue,b Takashi Inoueb and Noboru Onob
a Division of Synthesis and Analysis, Department of Molecular Science,
Integrated Center for Sciences (INCS), Ehime University, and CREST,
Japan Science Technology Corporation (JST), Matsuyama 790-8577, Japan.
E-mail: uno@dpc.ehime-u.ac.jp; Fax: ϩ81-89-927-9670; Tel: ϩ81-89-927-9660
b Department of Chemistry, Faculty of Science, Ehime University, Matsuyama 790-8577, Japan
Received 17th June 2003, Accepted 8th September 2003
First published as an Advance Article on the web 1st October 2003
Acid-catalyzed oligomerization of 2-(hydroxymethyl)pyrroles bearing C6F5, 2,6-Cl2C6H3, CF3 and CO2Et groups
at β-positions was examined. The reaction of ethyl pyrrole-3-carboxylates gave a mixture of oligomers and type I
isomers of porphyrinogens and hexaphyrinogens were isolated when the other β-substituents were sufficiently bulky,
for example, mesityl, 2,6-Cl2C6H3 and C6F5 groups. On the other hand, the pyrroles having other electron-withdrawing
groups afforded porphyrinogens as the only isolable products.
Introduction
Results and discussion
The preparation of porphyrins has attracted much attention
from an increasing number of scientists from many fields due
not only to their important biological roles but also because of
their applications as highly functional materials. For the latter
purpose, many excellent and reliable methods represented by
Lindsey, MacDonald, and [3 ϩ 1] porphyrin syntheses have
been developed.1,2 Above all, the Lindsey and related methods,
based on the cyclotetramerization of pyrroles with aldehydes or
the condensation of dipyrromethanes with aldehydes are the
best in terms of the versatility, efficiency and applicability of
preparations of a wide variety of meso-substituted porphyrins.1
In the Lindsey procedure, however, only pyrroles with the
same β-substituents can be employed as the pyrrolic unit, as
otherwise there is a great intrinsic problem with mixtures of
peripheral substitution-type isomers being formed. Moreover,
scrambling of the pyrrole units became a major problem in
porphyrinogen formation when different dipyrromethanes were
condensed.3 In order to prepare isomerically pure porphyrins
with a variety of substituents at the β-positions, methods
involving the tetrameric condensation of α-hydroxymethyl-
or α-aminomethyl-substituted pyrroles and the dimeric con-
densation of dipyrromethanes under mild conditions were
developed.4 Even in this case, the success of the synthesis
depended on the nature of the pyrrolic β-substituents: electron-
withdrawing groups tended to suppress pyrrole migration,
while electron-donating groups promoted the migration
yielding mixtures.5 We found that a combination of bulky and
electron-withdrawing substituents at the β-pyrrolic position is
successful in suppressing the problematic pyrrole migration in
the acid-catalyzed cyclo-oligomerization of α-hydroxymethyl-
pyrrole derivatives6 and we succeeded in the first isolation of
isomerically pure meso-unsubstituted porphyrinogens and
hexaphyrinogens.7 In this paper, we discuss the detailed study
of the cyclo-oligomerization reaction as well as the structural
elucidation of the porphyrinogens, hexaphyrinogens, and
porphyrins with electron-withdrawing groups.
Oligocyclization of 2-hydroxymethylpyrroles
Acid-catalyzed oligomerization of ethyl 2-(hydroxymethyl)-3-
(2,6-dichlorophenyl)pyrrole-4-carboxylate (2a, 0.04 M), which
was obtained by regioselective reduction of the corresponding
pyrrole-2,4-dicarboxylate 1a,8 was carried out by treatment
with p-toluenesulfonic acid (pTSA) in chloroform for 12 h to
give a rather intractable mixture. GPC analysis of this mixture
revealed the existence of two major components, which were
proven to be porphyrinogen (26%) and hexaphyrinogen (2%) by
column chromatographic isolation (Scheme 1). Isolation of
† Electronic Supporting Information Available: Ortep drawings of 3dؒ
2EtOH, 3dؒ2DMF, 3e, 3eؒ2H2O, 3gؒ2(i-PrOH), 3gؒ2DMFؒ2CHCl3, 4aؒ
4CHCl3, 4aؒ4PhCl, 5aؒ2PhCl, 5d, 5dؒ½PhCl, and 5e; packing diagrams
of 5d and 5dؒ½PhCl; and their X-ray analyses data in CIF format. See
http://www.rsc.org/suppdata/ob/b3/b307132d/
Scheme 1 Oligocyclization of 2-hydroxymethylpyrroles with electron-
withdrawing groups at the β-positions.
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
3857

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Table 1 Cyclo-oligomerization of pyrrole-2-carboxylates 1 via 2-
(hydroxymethyl)pyrroles 2
reaction mixture, and porphyrinogen 3h contaminated with
a small amount of porphyrin 5h was isolated in 20% yield
(Scheme 2). This mixture was oxidized by DDQ to give
porphyrin 5h with poor solubility in common solvents.
Yield (%)
Entry
1,2
Solvent (conc./M)
Acid (equiv.)
3 (5)a
4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
a
a
a
a
a
a
a
a
b
b
c
c
d
e
f
CHCl3 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.02)
C2H4Cl2 (0.02)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
C2H4Cl2 (0.04)
pTSA (0.5)
pTSA (0.5)
pTSA (1.0)
26
64
63
57
22
8
47
40
2
6
6
5
—
3
13
10
22
20
—
—
6
—
—
—
pTSA (1.0)
Sc(OTf )3 (1.0)
K-10 (1.0b)
TFA (1.0)
BF3ؒOEt2 (1.0)
pTSA (1.0)
(8)
(3)c
(20)c, d
BF3ؒOEt2 (1.0)
pTSA (1.0)
K-10 (1.0b) (5)c, e
pTSA (1.0)
pTSA (1.0)
pTSA (1.0)
pTSA (1.0)
19
17c
12
12
g
a Yields of 5 are given in the parentheses. b g mmolϪ1 c Oxidation
.
with p-chloranil or DDQ was carried out at room temperature after
termination of the oligomerization with Et3N. d An isomeric mixture
(3 : trace : 2 : 1) was obtained. e Only the type I isomer was obtained.
other components was not successful due to their instability,
although cyclic pentamer, heptamer, or higher oligomers
were formed, as diagnosed from the GPC chromatogram and
MALDI-TOF mass spectroscopy. In order to increase the
amounts of these products, the reaction conditions were tested
and the results are summarized in Table 1.
Scheme 2 Cyclo-oligomerization of pyridone-fused pyrrole.
Pyrrole-3,4-dicarboxylates 9 were prepared according to the
method reported by van Leusen.12 Cyclo-oligomerization of 9
with formaldehyde equivalents such as trioxane was performed
under several conditions similar to those listed in Table 1.
However, no reaction was observed under any of the reaction
conditions. Finally, we treated 9 with trioxane in TFA as the
solvent at room temperature overnight, and porphyrinogen
3i was obtained in 32% yield (Scheme 3). In this case, formation
of the hexaphyrinogen could not be detected by the MALDI-
TOF analysis of the reaction mixture. The porphyrinogen 3i
was oxidized with DDQ in refluxing toluene to give the
corresponding porphyrin octaester in 48% yield.
Use of pTSA (0.5–1.0 equiv.) as the acid catalyst, dichloro-
ethane as the solvent and a concentration of 2 of 0.02–0.04
mmol cmϪ3 gave the best results (entries 2–4). All hexa-
phyrinogens obtained were very stable toward oxidation even
on treatment with DDQ at room temperature, while only
porphyrinogens derived from pyrroles bearing a bulky electron-
deficient aromatic group, such as 2,6-dichlorophenyl and
pentafluorophenyl, were stable and these could be isolated by
chromatography (entries 1–8 and 13–16). Porphyrinogens with
phenyl and mesityl groups were readily oxidized to the corre-
sponding porphyrins 5b and 5c even during the workup
manipulation, and mixtures of porphyrinogens and porphyrins
were obtained. Therefore, the reaction mixtures were treated
with p-chloranil at room temperature before chromatographic
isolation (entries 10–12). When the acid was changed from
pTSA to acidic clay (K-10)4c in the reaction of 2c, only the type
I isomer of porphyrin 5c was obtained, although the yield was
poor (entry 12).
Two distinctive features emerged from Table 1. First, the
hexaphyrinogens were only isolated in the reactions of pyrroles
which had ester and bulky electron-withdrawing aromatic
groups at the β-positions. Secondly, the readily formed por-
phyrin 5c was a mixture of peripheral-substituted type isomers,
whereas the other porphyrinogens listed in Table 1 were
isomerically pure. These facts suggest that the bulkiness of the
aromatic substituents does not only suppress the pyrrole
isomerization process9 but also favours the structure of the
key intermediates in hexaphyrinogen formation in the cyclo-
oligomerization. The hexaphyrinogens showed a quite interest-
ing hexagonal columnar structure (discussed later), and would
be a new type of host molecules10 if the bulkiness of the aromatic
rings was reduced. We carried out the cyclo-oligomerization of
the following compounds.
Scheme 3 Cyclo-oligomerization of dibutyl pyrrole-3,4-dicarboxylate.
Pyridone-fused pyrrole 811 was synthesized from 3-nitro-2-
pyridone via p-methoxybenzyl-protection (PMB) followed by
the Barton–Zard reaction with ethyl isocyanoacetate, and
was subject to the cyclo-oligomerization reaction. None of
the corresponding hexaphyrinogens was formed even in the
X-Ray analysis of porphyrinogens
We attempted to prepare crystals for X-ray analysis by slow
evaporation of alcoholic (MeOH, EtOH, and i-PrOH) or
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
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Table 2 Crystallographic data for porphyrinogensa
Compound
3aؒ2(i-PrOH)b
3dؒ2EtOH
3dؒ2DMF
3e
3eؒ2H2O
3gؒ2(i-PrOH)
3gؒ2DMFؒCHCl3
Formula
FW
Temp./ЊC
System
Space group
a/Å
b/Å
c/Å
α/Њ
β/Њ
C62H60Cl8N4O10 C60H44F20N4O10 C62H46F20N6O10 C48H24Cl8F12N4 C48H28Cl8F12N4O2 C74H28F40N4O2 C75H27Cl3F40N6O2
1304.8
rt
1361.0
Ϫ150
1415.1
rt
1168.4
rt
Tetragonal
I41/a
15.963(1)
15.963(1)
20.165(2)
90
90
90
5138.3(6)
4
1204.4
rt
Tetragonal
I41/a
13.102(2)
13.102(2)
27.375(3)
90
90
90
4699(1)
4
1765.0
Ϫ100
Monoclinic
P21/n
18.886(2)
18.183(2)
9.886(2)
90
90.428(3)
90
3394.8(8)
2
1910.38
rt
Triclinic
Triclinic
Triclinic
Monoclinic
P21/n
15.679(3)
10.995(3)
23.426(2)
90
100.469(3)
90
3971(2)
2
¯
¯
¯
P1
P1
P1
12.571(6)
14.418(7)
9.414(4)
100.63(4)
95.88(4)
112.38(4)
1522(2)
1
8.728(1)
11.841(1)
14.930(2)
71.632 (9)
80.69(1)
81.70(1)
1437.9(3)
1
9.599(1)
11.653(2)
15.605(2)
110.08(1)
95.75(1)
106.70(1)
1531.5(4)
1
γ/Њ
V/Å3
Z
µ/cmϪ1
2θmax/Њ
3.89
123.2
1.49
55.0
1.44
55.0
5.20
55.0
5.74
55.0
1.81
50.7
3.62
55.0
Unique refln. 4728
6023
4923
0.021
448
0.055
0.066
0.126
1.403
7046
3256
0.039
467
0.061
0.106
0.159
1.104
3165
1394
2697
1507
6072
3725
9129
4033
No. obs.c
Rint
3168d
0.024
387
0.026
203
0.069
0.123
0.202
1.647
0.022
224
0.052
0.081
0.117
1.16
0.060
570
0.069
0.091
0.142
1.209
0.054
609
0.077
0.151
0.202
1.32
No. var.
R1
0.053d
0.053d
0.069d
1.980
e
Rf
wRg
GOF
a Unless otherwise noted, Mo-Kα was employed. b Cu-Kα was used. c I > 2σ(I ). d I > 3σ(I ). e R1 = Σ||Fo| Ϫ |Fc||/Σ|Fo| for I > 2σ(I ) data. f R = Σ(Fo2 Ϫ
Fc2)/ΣFo2 for all data. g wR = {Σ[w(Fo2 Ϫ Fc2)2]/Σ[w(Fo )2]}1/2 for all data.
2
chloroform solutions containing a small amount of DMF. In
some cases, suitable crystals for X-ray analysis were obtained
and the crystallographic data for successfully solved structures
of porphyrinogens are listed in Table 2.
between the water oxygen and two facing pyrrolic NH atoms
[NH ؒ ؒ ؒ O, 3.002(3) Å]. The angles between the pyrrole rings
and the mean plane of the meso-carbons are 56.0(1)Њ.
CCDC reference numbers 213884–213889.†
3gؒ2(i-PrOH). The porphyrinogen 3g occupies one of the
special positions (Ϫ1) and has a 1,2-alternate structure which is
constructed by hydrogen bonds between the i-PrOH oxygen
and two adjacent pyrrolic NH atoms [NH ؒ ؒ ؒ O, 2.964(3) and
2.944(3) Å]. The angles between the pyrrole rings and the mean
plane of the meso-carbons are 45.1(1)Њ and 54.5(1)Њ.
3aؒ2(i-PrOH)7. The porphyrinogen 3a occupies one of the
special positions (Ϫ1) and has a 1,2-alternate structure which is
constructed by hydrogen bonds between the i-PrOH oxygen
and two adjacent pyrrolic NH atoms [NH ؒ ؒ ؒ O, 2.950(4) and
3.022(3) Å]. The angles between the pyrrole rings and the mean
plane of the meso-carbons are 43.5(1)Њ and 58.8(1)Њ.
3gؒ2DMFؒ2CHCl3. The porphyrinogen 3g occupies one of
the special positions (Ϫ1) and has a 1,2-alternate structure
which is constructed by hydrogen bonds between the DMF
oxygen and two adjacent pyrrolic NH atoms [NH ؒ ؒ ؒ O,
2.819(4) and 2.843(3) Å]. The angles between the pyrrole rings
and the mean plane of the meso-carbons are 42.2(1)Њ and
47.6(1)Њ.
3dؒ2EtOH. The porphyrinogen 3d occupies one of the special
positions (Ϫ1) and has a 1,2-alternate structure which is
constructed by hydrogen bonds between the EtOH oxygen and
two adjacent pyrrolic NH atoms [NH ؒ ؒ ؒ O, 2.842(1) and
3.022(2) Å]. The angles between the pyrrole rings and the mean
plane of the meso-carbons are 59.98(6)Њ and 60.46(6)Њ.
Radial views from the centre of the porphyrinogen are shown
in Fig. 1. In the 1,2-alternate structures (3a, 3d, and 3g), the
angles between the pyrrole rings and the mean plane of
the meso-carbons are from 42.2(1)Њ to 60.46(6)Њ. The difference
between the angles in 3dؒ2EtOH is very small compared to
the others, which may be attributed to the steric effects of the
included solvent molecules: ethanol is smaller than i-PrOH and
DMF. The crystal structures of the meso-octasubstituted
porphyrinogens, namely calix[4]pyrroles,13 have been exten-
sively studied in order to prove their interesting anion-binding
ability14 and ability to π-donate to metal cations.15 In calix-
[4]pyrroles, 1,2-alternate and 1,3-alternate structures have often
been observed, while the cone structures have only been
reported when the calix[4]pyrroles were co-crystallized with
halide anions such as fluoride.16 In our case too, no cone struc-
ture was observed. The tendency to adopt the 1,2-alternate or
1,3-alternate structure remains unclear, and it is probably
affected by even a small change in the steric and electronic
properties of the substituents on the porphyrinogens and
included solvents.16 It is worthy to note that the cell volume of
3e is larger than that of 3eؒ2H2O. According to PLATON
calculations,17 there are eight solvent accessible areas (53 Å3
each) centered at specific positions (Ϫ1) in the unit cell of 3e.
Although the voids are large enough for water molecules, water
3dؒ2DMF. The porphyrinogen 3d occupies one of the special
positions (Ϫ1) and has a 1,2-alternate structure which is
constructed by hydrogen bonds between the DMF oxygen and
two adjacent pyrrolic NH atoms [NH ؒ ؒ ؒ O, 2.802(3) and
2.917(3) Å]. The angles between the pyrrole rings and the mean
plane of the meso-carbons are 42.05(11)Њ and 66.01(11)Њ.
3e and 3eؒ2H2O. Two types of crystals were obtained by slow
evaporation of the solvent from a solution of 3e in i-PrOH.
Elemental analysis showed that one molecule of water existed
in the crystals. First, a block crystal, which easily formed large
crystals, was subject to the X-ray analysis, and the crystal was
revealed to consist of only 3e. The porphyrinogen 3e in this
crystal occupies one of the special positions (Ϫ4) and has a 1,3-
alternate structure. The angles between the pyrrole rings and
the mean plane of the meso-carbons are 71.2(1)Њ. X-Ray analy-
sis of an octahedral crystal shows that this crystal of 3e
contains two molecules of water. The porphyrinogen 3e in this
crystal occupies one of the special positions (Ϫ4) and adopts
a 1,3-alternate structure. The oxygen atoms of the water mole-
cules sit on the special axis with (2.) symmetry which goes
through the center of 3e. Hydrogen bonds are observed
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
3859

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X-Ray analysis of hexaphyrinogens
Crystallographic data for successfully solved structures of
hexaphyrinogens 4 are listed in Table 3.
CCDC reference numbers 213890–213892.†
4aؒ4CHCl3. The hexaphyrinogen 4a occupies one of the
special positions (Ϫ1) and has a 1,3,5-alternate structure which
is constructed by intermolecular hydrogen bonds between the
pyrrolic NH and the ester oxygen on the adjacent pyrrole
ring [NH ؒ ؒ ؒ O, 2.894(5), 2.906(5), and 2.978(5) Å]. The
angles between the pyrrole rings and the mean plane of
the meso-carbons are 85.9(2)Њ, 87.2(2)Њ, and 88.4(2)Њ. Thus, the
hexaphyrinogen 4a in this crystal forms a hexagonal tubular
structure. Chloroform molecules occupy side areas between the
tubular hexaphyrinogen molecules with a disordered structure.
4aؒ4PhCl. The hexaphyrinogen 4a occupies one of the special
positions (Ϫ1) and has a 1,3,5-alternate structure which is
constructed by intermolecular hydrogen bonds between the
pyrrolic NH and the ester oxygen on the adjacent pyrrole ring
[NH ؒ ؒ ؒ O, 2.891(5), 2.891(5), and 2.913(5) Å]. The angles
between the pyrrole rings and the mean plane of the meso-
carbons are 87.0(1)Њ, 87.3(1)Њ, and 90.0(1)Њ. The structure of the
hexaphyrinogen 4a in this crystal is almost the same as that of
4aؒ4CHCl3.
7
4bؒCHCl3 . Crystallographically, two independent hexagonal
tube molecules of 4b exist in the unit cell, occupy special
positions with Ϫ3 and Ϫ1 symmetries, and adopt an almost
complete 1,3,5-alternate conformation. The solvent chloroform
molecules also occupy other Ϫ3 and Ϫ1 symmetric positions
with disordered structures. The pyrrole rings of 4b are almost
perpendicular to the mean plane of the six meso-methylenes
[88.8(1)Њ for the Ϫ3 structure; 82.8(2)Њ, 88.2(2)Њ, and 89.1(2)Њ
for the Ϫ1 structure]. The intramolecular hydrogen bond
[NH ؒ ؒ ؒ O, 2.842(5) Å for the Ϫ3 structure; 2.772(5), 2.894(5),
and 2.822(5) Å for the Ϫ1 structure] keeps this conformation
tight.
Radial views from the centre of the hexaphyrinogen are
shown in Fig. 2. In all 1,3,5-alternate structures, the angles
between the pyrrole rings and the mean plane of the meso-
Fig. 1 Radial views from the centre of the porphyrinogen. The
distances (Å) are calculated from the mean plane of the meso carbons.
Atoms labelled as 1 and 17 are the same meso carbon. (a) 3aؒ2(i-PrOH).
(b) 3dؒ2EtOH. (c) 3dؒ2DMF. (d) 3e. (e) 3eؒ2H2O. (f ) 3gؒ2(i-PrOH). (g)
3gؒ2DMFؒ2CHCl3.
may not be incorporated into this crystal because the voids are
surrounded by highly hydrophobic groups such as dichloro-
phenyl or trifluoromethyl groups. The dihedral angles between
the pyrrole planes and a plane made by the methylene carbon
and its adjacent pyrrolic α-carbons are similar and the values
are 54.0(1)Њ and 53.1(1)Њ. Therefore, the methylene protons are
nearly eclipsed with respect to the pyrrole planes and the
porphyrinogen in this structure forms an almost complete
saddle conformation (Fig. 1d). On the other hand, the angles
are 47.53(9)Њ and 64.40(9)Њ in the crystal of 3eؒ2H2O and the
porphyrinogen in this structure exists as a distorted saddle
conformation (Fig. 1e).
Fig. 2 Radial views from the centre of the porphyrinogen. The
distances (Å) are calculated from the mean plane of the meso-carbons.
Atoms labelled as 1 and 25 are the same meso-carbon. (a) 4aؒ4CHCl3.
(b) 4aؒ4PhCl. (c) 4bؒCHCl3.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
3860

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Table 3 Crystallographic data for hexaphyrinogensa
4aؒ4ClPhb
4bؒCHCl3
b
Compound
4aؒ4CHCl3
Formula
FW
Temp./ЊC
System
Space group
a/Å
b/Å
c/Å
α/Њ
C88H70Cl24N6O12
2254.4
Ϫ100
Orthorombic
Pbca
25.555(9)
15.884(9)
25.659(8)
90
C108H86Cl16N6O12
2227.2
rt
Monoclinic
P21/n
18.487(2)
15.093(2)
19.312(1)
90
C103H115Cl3N6O12
1735.4
Ϫ130
Trigonal
¯
R3
43.981(2)
43.981(1)
17.017(1)
90
β/Њ
90
90
10415(5)
4
6.84
51.4
6475
6472 [3785]
0.015
610 [518]
0.073 [0.087]
0.134 [0.093]
0.176 [0.248]
1.976 [1.136]
94.823(7)
90
5369.2(8)
2
4.71
55.0
12641
4422 [4324]
0.027
562 [514]
0.088 [0.062]
0.171 [0.148]
0.247 [0.201]
1.668 [0.820]
90
120
28507(2)
12
1.60
γ/Њ
V/Å3
Z
µ/cmϪ1
2θmax/Њ
Unique refln.
No. obs.c
Rint
55.0
14402
6480d
0.074
765
No. var.
e
R1
0.076d
0.076d
0.094d
1.739
Rf
wRg
GOF
a Mo-Kα was employed. b Values in brackets were obtained when the hexaphyrinogen molecule in the absence of solvent was refined by several
cycles of the SHELXL and PLATON-SQUEEZE programs. For detailed information, see the supporting information.† c I > 2σ(I ). d I > 3σ(I ).
e R1 = Σ||Fo| Ϫ |Fc||/Σ|Fo| for I > 2σ(I ) data. f R = Σ(Fo2 Ϫ Fc2)/ΣF for all data. g wR = {Σ[w(Fo2 Ϫ Fc2)2]/Σ[w(Fo )2]}1/2 for all data.
2
Table 4 Oxidation of Porphyrinogens
carbons are almost perpendicular and within a range from
82.8(2)Њ to 90.0(1)Њ, even though the space groups of the
crystals are different. The pyrrole β carbons bearing the ester
group are closer to the mean planes than the other β carbons
due to the hydrogen bonding with the adjacent pyrrolic protons.
The tight intramolecular hydrogen bonding is probably the
main reason for the structural differences between this and
calix[6]pyrrole,10e three 1,3,5-altenate pyrroles of which point
towards the center of the cavity. These hexaphyrinogen
structures are also refined in the absence of solvent molecules
by several cycles of the SHELXL refinement and the SQUEEZE
program of PLATON,17 and the results are also listed in Table
3. According to the PLATON calculation,17 there is a void
(59–66 Å3) in the center of the hexaphyrinogens. Although the
voids are large enough for small molecules such as water, no
molecule could be found by the differential Fourier map.
Porphyrinogen
Porphyrin
Yield (%)
3a
3d
3e
3f
3g
3i
5a
5d
5e
5f
5g
5i
66
38
50
38
Trace
48
Oxidation of porphyrinogens
The porphyrinogens 3 with electron-withdrawing groups were
oxidized by refluxing with DDQ in toluene or chloroform to
give isomerically pure porphyrins in good yields except for 3g
and the results are summarized in Table 4. In the case of 3g,
severe oxidation conditions caused the decomposition of the
starting material and/or product. Only trace amounts of the
porphyrin could be obtained in spite of all of our efforts. In
contrast to the porphyrinogens, the isolated hexaphyrinogens 4
were inert to oxidation. The isolated hexaphyrinogen 4a could
not be oxidized with DDQ either under reflux in toluene or in
the presence of an acid such as pTSA and BF3ؒOEt2.18 Some
good porphyrin crystals were obtained for X-ray analysis by
slow evaporation of the saturated solution of the porphyrins
in chlorobenzene or chloroform. Crystallographic data for
successfully solved structures of porphyrins 5 are listed in
Table 5.
NMR analysis of oligophyrinogens
In the proton NMR spectra of porphyrinogen 3a in CDCl3,
very broad signals due to meso-methylene protons were
observed at δ 3.1–4.9 at room temperature and became a sharp
AB-quartet at low temperatures. The coalescence temperatures
and approximate ∆E ‡ values for the conformational change
were ca. 35 ЊC and 58 kJ molϪ1 for 3a. For the other por-
phyrinogens, 3d, 3e, 3f and 3g, the meso-methylene proton
signals appeared as slightly broad singlets and showed almost
no change in the temperature range measured (Ϫ50 to 50 ЊC).
On the other hand, meso-methylene protons of hexaphyrinogens
4a, 4b and 4d in CDCl3 appeared as AB-quartets. Pyrrolic
protons appeared in rather lower fields compared to the parent
CCDC reference numbers 213893–213897.†
5aؒ2PhCl. The porphyrin 5a occupies one of the special
positions (Ϫ1) and the porphyrin ring is slightly distorted. The
porphyrin molecules do not stack due to the steric hindrance of
the dichlorophenyl groups which are nearly perpendicular to
the porphyrin ring [83.0(2)Њ and 83.5(1)Њ].
pyrroles and the stretching of NH and C᎐O in the IR spectra
᎐
supported the presence of intramolecular hydrogen bonding in
solution. The non-equivalence of the meso-protons in 4a and 4b
persisted in toluene-d8 solution even at 100 ЊC. On the other
hand, the meso-protons of 4d appeared as two broad singlet
signals at 50 ЊC in CDCl3, although the coalescence temper-
ature could not be measured due to poor solubility in toluene-
d8. These facts suggested that the hexagonal columnar structure
of the hexaphyrinogens was stabilized both by the intra-
molecular hydrogen bonding and by the steric effect of the
aromatic substituents.
5d. The space group is C2/c. Two porphyrin molecules stack
to form a dimeric structure and the porphyrin ring is distorted
in a cone structure due to the steric repulsion of peripheral
substituents in the dimeric form. The angles between the
porphyrin mean plane and the pentafluorophenyl group are
54.31(6)Њ, 59.47(6)Њ, 62.94(6)Њ, and 67.53(7)Њ.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
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Table 5 Crystallographic data for porphyrinsa
Compound
5aؒ2PhCl
5d
5dؒ½PhCl
5e
FW
1403.7
rt
1262.81
Ϫ100
Monoclinic
C2/c
21.856(3)
25.827(3)
19.842(3)
90
1319.1
Ϫ150
Monoclinic
C2/c
21.093(3)
25.700(3)
19.961(2)
90
1162.3
Ϫ100
Monoclinic
P21/a
14.995(3)
12.084(2)
15.045(3)
90
Temp./ЊC
System
Space group
a/Å
b/Å
c/Å
Monoclinic
P21/a
14.020(3)
18.711(3)
14.289(3)
90
α/Њ
β/Њ
117.76(1)
90
3317(1)
2
4.77
55.0
115.244(3)
90
10130(2)
8
1.60
55.0
11439
8310
0.042
793
0.051
107.100(3)
90
10342(2)
8
1.86
55.0
11738
8228
0.045
829
0.047
116.762(4)
90
2434.1(9)
2
5.48
55.0
5777
3298
0.038
337
0.074
0.115
0.178
1.665
γ/Њ
V/Å3
Z
µ/cmϪ1
2θmax/Њ
Unique refln.
No. obs.b
Rint
7608
3122
0.054
439
0.070
0.145
0.179
1.104
No. var.
c
R1
Rd
0.073
0.127
1.239
0.086
0.108
0.990
wRe
GOF
2
a Mo-Kα was employed. b I > 2σ(I ). c R1 = Σ||Fo| Ϫ |Fc||/Σ|Fo| for I > 2σ(I ) data. d R = Σ(Fo2 Ϫ Fc2)/ΣF for all data. e wR = {Σ[w(Fo2 Ϫ Fc2)2]/Σ[w(Fo )2]}1/2
for all data.
5dؒ½PhCl. Two porphyrin molecules stack to form a dimeric
structure and the porphyrin ring is distorted to form a dome
structure.19 The chlorobenzene molecule also occupies a special
position (Ϫ1) with a disordered structure on the concave face
of the porphyrin. The angles between the porphyrin mean
plane and the pentafluorophenyl group are 52.30(8)Њ, 56.30(7)Њ,
68.83(8)Њ, and 71.97(7)Њ.
interactions between the peripheral substituents. One dis-
ordered chlorobenzene molecule was caught between the
concave faces of the dimers in the crystal of 5dؒ½PhCl.
In conclusion, we have explored the acid oligomerization
of α-pyrrolylmethyl alcohols which gives porphyrinogens and
hexaphyrinogens. Substituents at the pyrrole β-positions played
an important role in product selectivity. Hexaphyrinogens were
successfully isolated only when both ester groups and bulky
aromatic groups, such as pentafluorophenyl, 2,6-dichloro-
phenyl, and mesityl, existed on the pyrrole. In these cases, the
formation of positional isomers was not observed for either
oligomer. When the substituents were bulky aromatic and
trifluoromethyl groups, porphyrinogens were formed as the
only isolable product. X-Ray and NMR structural analyses
revealed that the structures of the meso-unsubstituted por-
phyrinogens were very flexible and showed various types of
conformations even in the solid state, while the structures of
the hexaphyrinogens adopted a rigid hexagonal columnar
conformation constructed by intramolecular hydrogen bonds.
The porphyrinogens obtained could be converted to the corre-
sponding isomerically pure porphyrins.
5e. The porphyrin 5e occupies one of the special positions
(Ϫ1) and the porphyrin ring is slightly distorted. The porphyrin
molecules do not stack due to the steric hindrance of the
dichlorophenyl groups which are nearly perpendicular to the
porphyrin ring [84.4(1)Њ and 85.3(1)Њ].
Porphyrins with bulky 2,6-dichlorophenyl groups 5a and
5e were almost flat but slightly undulated to adopt a wave
conformation (Fig. 3).19 On the other hand, porphyrins with
pentafluorophenyl groups formed π-stacking dimers facing
the convex faces of the dome structure due to the repulsive
Experimental
Melting points are uncorrected. Unless otherwise specified,
NMR spectra were obtained with a JEOL GSX-270 or EX-400
spectrometer at ambient temperature by using CDCl3 as solvent
1
and tetramethylsilane as the internal standard for H and 13C
NMR. Mass spectra were measured with a Hitachi M80B [EI
(electron impact, 20 eV) and CI (chemical ionization, 70 eV,
isobutane as CI gas)], JEOL MStation [EI (electron impact, 20
eV), CI (chemical ionization, 70 eV, isobutane as CI gas), and
FAB (nitrobenzyl alcohol as the matrix)], or Voyager-DE
Pro (MALDI-TOF, sinapinic acid as the calibration matrix)
spectrometer. THF was distilled from sodium benzophenone
ketyl and dichloromethane was distilled from CaH2 prior to
use. DMF was distilled under reduced pressure and then stored
over MS 4A. Pyridine was distilled from CaH2 and stored
over MS 4A. Deuterated solvents were used without further
purification. DBU, chlorobenzene and hexane were distilled
prior to use. Chloroform was successively treated with sulfuric
acid, water, saturated sodium hydrogencarbonate, and calcium
chloride, passed through an alumina column, and distilled. In
Fig. 3 Distortion of porphyrins. The numerals represent the distances
(Å) from the mean porphyrin plane.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
3862

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the nomenclature of 4, we encountered difficulty about the
choice of the oxidation state for the so-called hexaphyrin which
had two oxidation states. Therefore, we have called the cyclic
hexa(pyrrolylmethyl) compounds hexaphyrinogen, the number-
ing of which is similar to that of porphyrin. Similarly, the cyclic
tetra(pyrrolylmethyl) compound was named as porphyrinogen,
although it is 5,10,15,20,22,23-hexahydro-21H,23H-porphine
in IUPAC nomenclature. The melting point is not indicated
when the melting point of a compound exceeded the upper
limit of the apparatus (250 ЊC). Ethyl pyrrole-2-carboxylates
1b,6b 1c,8 1e,8 1f8 and 1g20 were prepared according to the
literature procedures.
to the procedure described above to give 1.240 g (66%) of the
title pyrrole as colorless crystals, mp 116–117 ЊC; δH (CDCl3)
10.50 (1H, br s), 7.69 (1H, d, J = 3.4 Hz), 4.22 (4H, m), 1.22
(3H, t, J = 6.8 Hz) and 1.17 (3H, t, J = 6.8 Hz); δC (CDCl3)
163.0, 160.1, 144.6 (dm, J = 243 Hz), 140.7 (dm, J = 253 Hz),
137.2 (dm, J = 251 Hz), 127.6, 122.6, 117.7, 114.1, 109.4 (td,
J = 4 and 18 Hz), 61.2, 60.3, 13.9 and 13.7; δF (CDCl3) Ϫ139.4
(2F, m), Ϫ156.4 (1F, m) and Ϫ164.8 (2F, m); νmax (KBr)/cmϪ1
3271, 1724, 1697, 1506, 1281 and 1196; MS (EI) m/z 377 (Mϩ,
81), 332 (58) and 286 (100) (Found: C, 50.88; H, 3.28; N, 3.76.
C16H12F5NO4 requires C, 50.94; H, 3.21; N, 3.71%).
General procedure for acid-catalyzed cyclo-oligomerization
(Table 1)
Diethyl 3-(2,6-dichlorophenyl)pyrrole-2,4-dicarboxylate (1a)
A solution of 2,6-dichlorobenzaldehyde (43.75 g, 250 mmol),
ethyl tosylacetate (48.40 g, 200 mmol), piperidine (1.0 mL), and
acetic acid (3.0 mL) in toluene (150 mL) was refluxed with
a Dean–Stark apparatus, and water was removed. When the
distillate did not separate, piperidine (1.0 mL) and acetic acid
(3.0 mL) were added, and the reflux was continued. After 3
days, the reaction was quenched by the addition of water. The
organic layer was separated and the aqueous layer was
extracted with toluene. The combined organic layer was washed
successively with diluted HCl (1.0 M), water, sat. NaHCO3, and
brine, dried over Na2SO4, and concentrated. The residue was
chromatographed on silica gel (15% EtOAc–hexane) to give a
white solid. Recrystallization from CH2Cl2–hexane gave 27.86 g
(32%) of ethyl (Z)-3-(2,6-dichlorophenyl)-2-tosyl-2-propenoate
as white crystals, mp 89 ЊC; δH (CDCl3) 8.27 (1H, s), 7.91 (2H,
m), 7.32 (4H, m), 7.27 (1H, m), 4.00 (2H, q, J = 7.3 Hz), 2.46
(3H, s) and 0.91 (3H, J = 7.3 Hz); δC (CDCl3) 160.3, 144.7,
143.4, 139.5, 136.4, 133.2, 131.4, 130.4, 129.5, 128.6, 127.8,
61.8, 21.6 and 13.2; νmax (KBr)/cmϪ1 1722, 1323, 1151 and 781;
MS (DI-EI) m/z 399 (Mϩ, 88), 353 (100) and 243 (13) (Found:
C, 54.12; H, 4.02. C18H16Cl2O4S requires C, 54.14; H, 4.04%).
To a stirred solution of the tosylpropenoate (1.99 g, 5.0 mmol)
and ethyl isocyanoacetate (0.75 mL, 7.5 mmol) in dry THF (20
mL) was slowly added freshly distilled DBU (1.0 mL, 10 mmol)
at 0 ЊC under argon. The mixture was allowed to warm to room
temperature and stirred for 12 h. Dilute HCl (1.0 M) was added
and the mixture was extracted with EtOAc. The organic extract
was washed with water and brine, dried over Na2SO4, and con-
centrated. The residue was chromatographed on silica gel
(CHCl3) to give 1.21 g (68%) of the title compound as colorless
crystals, mp 164–166 ЊC; δH (CDCl3) 10.32 (1H, br s), 7.67 (1H,
d, J = 3.4 Hz), 7.36–7.20 (3H, m), 4.17–4.08 (4H, m), 1.08 (3H,
t, J = 7.0 Hz) and 1.01 (3H, t, J = 7.0 Hz); δC (CDCl3) 163.4,
160.7, 135.2, 133.7, 128.6, 127.4, 127.0, 125.9, 121.3, 116.9,
60.7, 59.8, 13.8 and 13.6; νmax (KBr)/cmϪ1 3296, 1716, 1684,
1282, 1190 and 1036; MS (EI) 355 (Mϩ, 14), 320 (100), 274 (64)
and 246 (45) (Found: C, 53.89; H, 4.24; N, 3.99. C16H15Cl2NO4
requires C, 53.95; H, 4.24; N, 3.93%).
Ethyl pyrrole-2-carboxylate (1; 2.0 mmol) was treated with
LiAlH4 (2.0 mmol) in THF (10 mL) at 0 ЊC for 1 h. The reaction
was quenched by addition of aq. NaOH. The supernatant
solution was concentrated to give the corresponding 2-hydroxy-
methylpyrrole 2, which was used without purification. The
crude 2-hydroxymethylpyrrole 2 was treated with an acid in a
dry solvent (50 mL) at room temperature under the conditions
listed in Table 1. After the disappearance of 2, as determined by
TLC, the reaction was quenched by neutralization with Et3N.
The mixture was washed with saturated NaHCO3 and brine,
dried over MgSO4, and concentrated in vacuo to give a syrupy
solid, which was chromatographed on silica gel. In some cases,
oxidation was carried before the chromatography as follows.
The residue was dissolved in dichloromethane (50 mL),
chloranil or DDQ (4 mmol) was added and the mixture was
stirred for 12 h. After removal of the solvent, the residue was
chromatographed on silica gel.
Tetraethyl 3,8,13,18-tetrakis(2,6-dichlorophenyl)porphyrino-
gen-2,7,12,17-tetracarboxylate (3a). White powder; δH
(CDCl3) 8.35 (4H, br s), 7.39–7.20 (12H, m), 4.9–3.1 (8H, br s),
4.06 (8H, q, J = 7.3 Hz) and 0.98 (12H, t, J = 7.3 Hz); δC
(CDCl3) 164.5, 136.5, 135.9, 133.9, 129.0, 127.7, 127.2, 117.4,
110.9, 59.4, 22.6 and 13.8; νmax (KBr)/cmϪ1 3265, 1705, 1674,
1541, 1429, 1186, 1088 and 781; MS (FABϩ) m/z 1185 (Mϩ ϩ 1)
(Found: C, 56.66; H, 3.67; N, 4.67. Anal. C56H44Cl8N4O8
requires C, 56.78; H, 3.74; N, 4.73%).
Hexaethyl
3,8,13,18,23,28-hexakis(2,6-dichlorophenyl)-
hexaphyrinogen-2,7,12,17,22,27-hexacarboxylate (4a). White
powder; δH (DMSO-d6) 10.6 (6H, br s), 7.31–7.18 (18H, m),
4.10–3.76 (24H, m) and 0.83 (18H, m); δC (DMSO-d6) 166.9,
135.8, 135.0, 128.3, 127.2, 126.9, 116.1, 109.9, 98.9, 59.3, 24.0
and 13.5; νmax (KBr)/cmϪ1 3330, 2978, 1707, 1674, 1429, 1304,
1190, 1097 and 783; MS (FABϩ) m/z 1777 (Mϩ ϩ 1) (Found: C,
56.71; H, 3.60; N, 4.72. C84H66Cl12N6O12 requires C, 56.78; H,
3.74; N, 4.73%).
Tertaethyl 3,8,13,18-tetrakis(2,6-dichlorophenyl)-21H,23H-
porphine-2,7,12,17-tetracarboxylate (5a). Purple crystals; δH
(CDCl3) 10.84 (4H, s), 7.80–7.62 (12H, m), 4.52 (8H, q, J = 7.0
Hz), 1.23 (12H, t, J = 7.0 Hz) and Ϫ2.48 (2H, s); δC (CDCl3)
164.0, 146.5, 144.5, 143.5, 136.4, 134.3, 130.9, 130.5, 128.1,
105.5, 61.2 and 13.9; νmax (KBr)/cmϪ1 2981, 1716, 1558, 1429,
1184, 1084 and 783; MS (FABϩ) m/z 1179 (Mϩ ϩ 1); λmax
(CHCl3)/nm (log10 ε/L molϪ1 cmϪ1) 660 (4.08), 606 (4.26), 563
(4.23), 528 (4.55) and 437 (5.58) (Found: C, 56.99; H, 3.36; N,
4.76. C56H38Cl8N4O8 requires C, 57.07; H, 3.25; N, 4.75%).
Diethyl 3-(pentafluorophenyl)pyrrole-2,4-dicarboxylate (1d)
Pentafluorobenzaldehyde (45.10 g, 230 mmol) and ethyl tosyl-
acetate (48.40 g, 200 mmol) were reacted according to the
procedure described above to give 68.90 g (82%) of ethyl (Z)-3-
pentafluorophenyl-2-tosyl-2-propenoate as yellow crystals, mp
87 ЊC; δH (CDCl3) 7.99 (1H, s), 7.85 (2H, m), 7.37 (2H, m), 4.17
(2H, q, J = 7.3 Hz), 2.47 (3H, s) and 1.15 (3H, t, J = 7.3 Hz);
δC (CDCl3) 160.8, 145.4, 144.4 (dm, J = 253 Hz), 142.4 (dm,
J = 259 Hz), 141.8, 137.8 (dm, J = 255.1 Hz), 135.7, 129.9,
129.7, 128.9, 108.9 (td, J = 17 and 4 Hz), 62.5, 21.6 and 13.4;
δF (CDCl3) Ϫ136.5 (2F, m), Ϫ149.6 (1F, m) and Ϫ161.3 (2F, m);
νmax (KBr)/cmϪ1 1734, 1523, 1500, 1329, 1155 and 982; MS (CI)
m/z 421 (Mϩ ϩ 1, 95), 375 (100), 356 (28) and 327 (4) (Found:
C, 51.68; H, 3.33. C18H13F5O4S requires C, 51.43; H, 3.12%).
The reaction of tosylpropenoate (2.102 g, 5.0 mmol) and ethyl
isocyanoacetate (0.75 mL, 7.5 mmol) was carried out according
Hexaethyl
3,8,13,18,23,28-hexakis(2,4,6-trimethylphenyl)-
hexaphyrinogen-2,7,12,17,22,27-hexacarboxylate (4b). White
crystals; δH (CDCl3) 9.81 (6H, br s), 6.85 (6H, s), 6.71 (6H, s),
4.06 (6H, d, J = 15.0 Hz), 4.04 (12H, m), 3.18 (6H, d, J = 15.0
Hz), 2.27 (18H, s), 1.88 (18H, s), 1.72 (18H, br s) and 0.89 (18H,
t, J = 7.2 Hz); δC (CDCl3) 167.6, 138.7, 136.3, 135.6, 132.4,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
3863

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127.2, 127.0, 126.3, 119.6, 110.1, 59.3, 23.8, 22.0, 20.8, 20.5,
13.5 and one sp2 carbon was not found; MS (FABϩ) m/z = 1615
(Mϩ ϩ 1) (Found: C, 75.44; H, 7.11; N, 5.11. C102H114N6O12
requires C, 75.81; H, 7.11; N, 5.20%).
J = 2 Hz), 107.6 (q, J = 33 Hz), 22.0; δF (CDCl3) Ϫ55.1 (s);
νmax (KBr)/cmϪ1 3302, 1158, 1431, 1394, 1358, 1157, 1142, 1051,
987 and 793; MS (FABϩ) m/z 1168 (Mϩ) (Found: C, 48.60; H,
2.24; N, 4.75. C48H24Cl8F12N4 ϩ H2O requires C, 48.60; H, 2.21;
N, 4.72%).
Tetraethyl
3,8,13,18-tetrakis(2,4,6-trimethylphenyl)-21H,-
2,7,12,17-Tetrakis(2,6-dichlorophenyl)-3,8,13,18-tetrakis-
(trifluoromethyl)-21H,23H-porphine (5e). Purple crystals; δH
(CDCl3) 9.98 (4H, s), 7.81–7.68 (12H, m) and Ϫ2.79 (2H, br s);
νmax (KBr)/cmϪ1 1520, 1496, 1329, 1128 and 989 cmϪ1; MS
23H-porphine-2,7,12,17-tetracarboxylate (5b). Purple crystals;
δH (CDCl3) 10.69 (4H, s), 7.26 (8H, s), 4.50 (8H, q, J = 7.3 Hz),
2,55 (12H, s), 2.11 (24H, s), 1.22 (12H, t, J = 7.3 Hz) and Ϫ2.74
(2H, br s); δC (CDCl3) 164.6, 139.6, 137.9, 137.3, 137.5, 137.3,
132.7, 128.2, 104.5, 61.3, 21.4, 21.3, 13.6 and one sp2 carbon
was not found; νmax (KBr)/cmϪ1 3444, 3307, 2977, 1718, 1226
and 1184; MS (FABϩ) m/z 1071 (Mϩ ϩ 1); λmax (CH2Cl2)/nm
(log10 ε//L molϪ1 cmϪ1) 652 (3.49), 596 (3.85), 559 (3.80), 523
(4.32) and 432 (5.48) (Found: C, 75.06; H, 6.65; N, 5.23.
C68H70N4O8 ϩ H2O requires C, 74.98; H, 6.66; N, 5.14%).
(FABϩ) m/z 1163 (Mϩ); λmax (CHCl3)/nm (log10 ε/L molϪ1 cmϪ1
)
640 (4.07), 585 (4.22), 540 (4.19), 508 (4.48) and 414 (5.53)
(Found: C, 49.21; H, 1.68; N, 4.70. C48H18Cl8F12N4 requires C,
49.60; H, 1.56; N, 4.82%).
2,7,12,17-Tetrakis(pentafluorophenyl)-3,8,13,18-tetrakis-
(trifluoromethyl)porphyrinogen (3f). White crystals, mp 129–
131 ЊC; δH (CDCl3) 9.54 (4H, br s) and 3.87 (8H, br s);
δC (CDCl3) 144.9 (dm, J = 245 Hz), 141.3 (dm, J = 257 Hz),
137.7 (dm, J = 255 Hz), 130.8 (q, J = 2 Hz), 125.6, 123.6 (q,
J = 268 Hz), 110.4 (q, J = 35.0 Hz), 107.5 (td, J = 19 and 4 Hz),
105.7 and 23.0; δF (CDCl3) Ϫ55.8 (12F, s), Ϫ139.7 (8F, m),
Ϫ153.5 (4F, m) and Ϫ161.9 (8F, m); νmax (KBr)/cmϪ1 3288,
1519, 1496, 1155, 1128, 1109 and 987; MS (FABϩ) m/z 1252
(Mϩ) (Found: C, 45.95; H, 1.15; N, 4.42. C48H18Cl8F12N4
requires C, 46.03; H, 0.97; N, 4.47%).
Tetraethyl 3,8,13,18-tetraphenyl-21H,23H-porphine-2,7,12,-
17-tetracarboxylate (5c). Purple powder; isomeric mixture
(3 : trace : 2 : 1); type I isomer: δH (CDCl3) 10.89 (4H, s), 8.10–
8.14 (8H, m), 7.72–7.85 (12H, m), 4.55 (8H, q, J = 7.3 Hz),
1.26 (12H, t, J = 7.3 Hz) and Ϫ2.92 (2H, s); type II isomer:
δH (typical signals) 11.79 (2H, s) and 9.89 (2H, s); type III
isomer: δH (typical signals) 10.82 (1H, s), 10.86 (2H, m) and
9.89 (1H, s); type IV isomer: δH (typical signals) 10.82 (2H, s)
and 10.86 (2H, s); MS (FABϩ) m/z = 903 (Mϩ ϩ 1) (Found: C,
65.39; H, 4.81; N, 4.87. C56H46N4O8 ϩ 2CH2Cl2 requires C,
64.93; H, 4.70; N, 5.22%).
2,7,12,17-Tetrakis(pentafluorophenyl)-3,8,13,18-tetrakis-
(trifluoromethyl)-21H,23H-porphine (5f). Purple crystals; δH
(CDCl3) 10.18 (4H, s) and Ϫ2.87 (2H, br s); δF (CDCl3) Ϫ136.9
(12F, s), Ϫ148.8 (8F, m), Ϫ152.7 (4F, m) and Ϫ160.1 (8F, m);
νmax (KBr)/cmϪ1 3444, 1519, 1496, 1086, 993 and 941; MS
(MALDI-TOF) m/z 1247 (Mϩ ϩ 1); λmax (CHCl3)/nm (log10 ε/L
molϪ1 cmϪ1) 643, 589, 541, 509 and 416 [HRMS (FABϩ) Found:
1247.0164. C48H6F32N4 ϩ Hϩ requires 1247.0160].
Tetraethyl
3,8,13,18-tetrakis(pentafluorophenyl)porphyr-
inongen-2,7,12,17-tetracarboxylate (3d). Light brown crystals;
δH (CDCl3) 8.40 (4H, br s), 4.16 (8H, q, J = 6.8 Hz), 4.03 (8H, br
s) and 1.04 (12H, t, J = 6.8 Hz); δC (CDCl3) 164.7, 144.9 (dm,
J = 243 Hz), 140.6 (dm, J = 253 Hz), 137.5 (dm, J = 249 Hz),
136.1, 128.8, 111.9, 109.8 (td, J = 18 and 4 Hz), 105.3, 60.1, 23.4
and 13.7; δF (CDCl3) Ϫ140.6 (8F, m), Ϫ155.5 (4F, m) and
Ϫ163.3 (8F, m); νmax (KBr)/cmϪ1 3440, 1720, 1088 and 991
cmϪ1; MS (MALDI-TOF) m/z 1268 (Mϩ) (Found: C, 52.84; H,
2.71; N, 4.44. C56H32F20N4O8 requires C, 53.01; H, 2.54; N,
4.42%).
2,3,7,8,12,13,17,18-Octakis(pentafluorophenyl)porphyrinogen
(3g). White crystals, mp 150–152 ЊC; δH (CDCl3) 9.45 (4H, br s)
and 3.71 (8H, s); δC (CDCl3) 144.4 (dm, J = 242 Hz), 140.7 (dm,
J = 252 Hz), 137.8 (dm, J = 252 Hz), 128.8, 108.2 (td, J = 19 and
4 Hz), 106.9 and 23.6; δF (CDCl3) Ϫ141.7 (16F, m), Ϫ153.7 (8F,
m), and Ϫ160.9 (16F, m); νmax (KBr)/cmϪ1 3454, 1519, 1491,
1061, 991 and 839; MS (MALDI-TOF) m/z 1645 (Mϩ ϩ 1)
(Found: C, 49.65; H, 1.50; N, 3.26. C68H12F40N4 ϩ 2EtOH
requires C, 49.79; H, 1.39; N, 3.23%).
Hexaethyl 3,8,13,18,23,28-hexakis(pentafluorophenyl)hexa-
phyrinogen-2,7,12,17,23,28-hexacarboxylate (4d). Light brown
crystals; δH (CDCl3) 10.57 (6H, br s), 4.20 (6H, br d, J = 14.9
Hz), 3.99 (12H, q, J = 7.3 Hz), 3.34 (6H, br d, J = 14.9 Hz) and
1.11 (18H, t, J = 6.8 Hz); δF (CDCl3) Ϫ138.1 (6F, br s), Ϫ139.0
(6F, m), Ϫ157.4 (6F, m), Ϫ163.8 (6F, m) and Ϫ164.9 (6F, br s);
νmax (KBr)/cmϪ1 3225, 1678, 1492 and 987; MS (ESI-TOF) m/z
1903 (Mϩ) [HRMS (FABϩ) Found: 1903.2941. C84H48F30N6O12
ϩ Hϩ requires 1903.2930].
2,3,7,8,12,13,17,18-Octakis(pentafluorophenyl)-21H,23H-
porphine (5g). MS (FABϩ) m/z 1639 (Mϩ ϩ 1); λmax (CHCl3)/nm
644, 591, 548, 515 and 426 [HRMS (FABϩ) Found: 1639.0045.
C68H6F40N4 ϩ Hϩ requires 1639.0032].
Tetraethyl 3,8,13,18-tetrakis(pentafluorophenyl)-21H,23H-
porphine-2,7,12,17-tetracarboxylate (5d). Purple crystals; δH
(CDCl3) 11.03 (4H, s), 4.68 (8H, q, J = 6.8 Hz), 1.45 (12H, t,
J = 6.8 Hz) and Ϫ2.51(2H, br s); δC (CDCl3) 163.5, 145.2 (dm,
J = 248 Hz), 142.2 (dm, J = 257 Hz), 138.0 (dm, J = 254 Hz),
109.8 (td, J = 18 and 4 Hz) 106.1, 61.9, 13.9 and pyrrolic
carbons could not be found; δF (CDCl3) Ϫ137.1 (8F, m),
Ϫ151.9 (4F, m) and Ϫ161.8 (8F, m); νmax (KBr)/cmϪ1 3440,
1720, 1088 and 991; MS (MALDI-TOF) m/z 1263 (Mϩ); λmax
(CHCl3)/nm (log10 ε/L molϪ1 cmϪ1) 663 (3.94), 612 (4.06), 564
(4.01), 529 (4.28) and 439 (5.22) (Found: C, 53.13; H, 2.20; N,
4.51. C90H28F20N4O8 requires C, 53.26; H, 2.08; N, 4.44%).
Porphyrinogen bearing 2-pyridone (3h). Black solid; δH
(CDCl3) 11.85 (4H, br s), 7.09 (8H, m), 6.85 (8H, m), 6.28 (4H,
d, J = 7.3 Hz), 6.23 (4H, d, J = 7.3 Hz), 5.35 (4H, d, J = 14.9
Hz), 4.64 (4H, d, J = 15.1 Hz), 4.49 (4H, d, J = 14.9 Hz), 3.90
(4H, d, J = 14.9 Hz) and 3.81 (12H, s); δC (CDCl3) 162.8, 158.9,
130.0, 129.0, 128.7, 126.1, 120.2, 119.8, 114.3, 110.4, 101.0,
55.3, 48.9 and 23.5; νmax (KBr)/cmϪ1 2929, 1643, 1599, 1512,
1248 and 727; MS (MALDI-TOF) m/z 1065 (Mϩ ϩ 1) [HRMS
(FABϩ) Found: 1064.4213. C64H58N8O8 requires 1064.4221].
Di-n-butyl pyrrole-3,4-dicarboxylate (9). White crystal, mp
102–103 ЊC; δH (CDCl3) 10.61 (1H, br s), 7.42 (2H, s), 4.23 (4H,
q, J = 6.8 Hz), 1.69 (4H, m), 1.42 (4H, m), and 0.95 (6H, t,
J = 7.3 Hz); δC (CDCl3) 164.3, 126.7, 115.2, 64.0, 30.7, 19.2 and
13.7; νmax (KBr)/cmϪ1 3265, 1716, 1286, 1053 and 796; MS (EI)
m/z 267 (Mϩ, 7), 212 (10), 194 (24), 138 (100) (Found: C, 62.81;
H, 7.77; N, 5.20. C14H21NO4 requires C, 62.90; H, 7.92; N,
5.24%).
2,7,12,17-Tetrakis(2,6-dichlorophenyl)-3,8,13,18-tetra-
kis(trifluoromethyl)porphyrinogen (3e). White crystals, mp
133–135 ЊC; δH (CDCl3) 8.27 (4H, br s), 7.49–7.21 (12H, m) and
4.01–3.35 (8H, br s); δC (DMSO-d6) 136.1, 131.2, 129.8, 128.3
(q, J = 4.0 Hz), 127.3, 124.5, 123.9 (q, J = 268 Hz), 114.5 (q,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
3864

View Article Online
J. Chem. Soc., Perkin Trans. 1, 1998, 1531–1539; (c) C. J. Hawker,
Octabutyl porphyrinogen-2,3,7,8,12,13,17,18-octacarboxylate
(3i). Di-n-butyl pyrrole-3,4-dicarboxylate (0.535 g, 2.0 mmol)
and trioxane (0.072 g, 2.0 mmol) were dissolved in TFA (12
mL) at room temperature and the mixture was refluxed for
2 days. The reaction was quenched by aq. NaHCO3 and the
mixture was extracted with chloroform. The organic extract
was washed with brine, dried over Na2SO4, and concentrated.
The residue was chromatographed on silica gel (EtOAc–
hexane) to give 0.180 g (32%) of the title compound as a pale
brown solid; δH (CDCl3) 9.89 (4H, br s), 4.20 (24H, m), 2.35
(16H, br s), 1.66 (16H, m), 1.37 (16H, m) and 0.94 (24H, t,
J = 7.3 Hz); δC (CDCl3) 165.5, 133.7, 112.1, 64.6, 30.6, 23.2,
19.2 and 13.7; νmax (KBr)/cmϪ1 2929 and 1643; MS (FABϩ)
m/z 1117 (Mϩ ϩ 1) [HRMS (FABϩ) Found: 1117.5945.
C60H84N4O16 ϩ Hϩ requires 1117.5961].
P. M. Petersen, F. J. Leeper and A. R. Battersby, J. Chem. Soc.,
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Handbook, eds. K. M. Kadish, K. M. Smith and R. Guilard,
Academic Press, New York, 2000, vol. 6, ch. 45.
Octabutyl
21H,23H-porphin-2,3,7,8,12,13,17,18-octacarb-
oxylate (5i). Black solid; δH (CDCl3) 11.22 (4H, s), 4.86 (16H, t,
J = 7.8 Hz), 2.09 (16H, m), 1.71 (16H, m), 1.13 (24H, t, J = 7.3
Hz) and Ϫ2.94 (2H, br s); δC (CDCl3) 164.8, 130.9, 128.8, 106.5,
66.5, 30.9, 19.4 and 13.9; νmax (KBr)/cmϪ1 3313 and 1728; MS
(FABϩ) 1111 (Mϩ ϩ 1); λmax (CHCl3)/nm 663, 607, 560, 527 and
434 [HRMS (FABϩ) Found: 1111.5500. C60H78N4O16 ϩ Hϩ
requires 1111.5491].
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Acknowledgements
This work was partially supported by Grant-in-Aids for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology of Japan. We appreciate the
Research Center for Molecular Materials, the Institute for
Molecular Science for carrying out X-ray measurements
(RAXIS-IV and AFC7R-Mercury CCD). The experimental
assistance of Miss Yuko Yamashita is greatly acknowledged.
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O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 8 5 7 – 3 8 6 5
3865