The first isolation of unsubstituted porphyrinogen and unsubstituted 21-oxaporphyrinogen by the '3+1' approach from 2,5-bis(hydroxymethyl)pyrrole and tripyrrane derivatives

Article abstract of DOI:10.1016/S0040-4020(01)00059-X

The treatment of 2,5-bis(hydroxymethyl)pyrrole or 2,5-bis(hydroxymethyl)furan with pyrrole in the presence of hydrochloric acid gave tripyrrane and 2,5-bis(2-pyrrolylmethyl)furan in 58-61% yield, which afforded the simplest porphyrinogen (hexahydroporphine) and 21-oxaporphyrinogen by the '3+1' approach in 14 and 11% yields, respectively. 21-Oxaporphyrinogen has been shown to adopt a 1,2-alternated conformation in the solid state by X-ray crystallography.

Full text of DOI:10.1016/S0040-4020(01)00059-X

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 2103±2108
The ®rst isolation of unsubstituted porphyrinogen and
unsubstituted 21-oxaporphyrinogen by the `311' approach from
2,5-bis(hydroxymethyl)pyrrole and tripyrrane derivatives
a,p
Shozo Taniguchi, Hikaru Hasegawa, Shoko Yanagiya, Yusuke Tabeta, Yoshiharu Nakano
b
b
b
c
a
and Masahiko Takahashi
a
Department of Materials Science, Faculty of Engineering, Ibaraki University, Hitachi, Ibaraki 316-8511, Japan
Department of Chemistry and Material Engineering, Ibaraki National College of Technology, Hitachinaka, Ibaraki 312-8508, Japan
b
c
Department of Natural Material Science, Faculty of Science, Ibaraki University, Mito, Ibaraki 310-8512, Japan
Received 20 November 2000; accepted 11 January 2001
AbstractÐThe treatment of 2,5-bis(hydroxymethyl)pyrrole or 2,5-bis(hydroxymethyl)furan with pyrrole in the presence of hydrochloric
acid gave tripyrrane and 2,5-bis(2-pyrrolylmethyl)furan in 58±61% yield, which afforded the simplest porphyrinogen (hexahydroporphine)
and 21-oxaporphyrinogen by the `311' approach in 14 and 11% yields, respectively. 21-Oxaporphyrinogen has been shown to adopt a 1,2-
alternated conformation in the solid state by X-ray crystallography. q 2001 Elsevier Science Ltd. All rights reserved.
1
. Introduction
bridged trimer of phenols by the condensation of 2,6-bis-
hydroxymethyl)-4-substituted phenols with excess 4-sub-
(
`
Porphine' and its precursor `porphyrinogen' are often cited
stituted phenols in the presence of hydrochloric acid. The
trimers were then converted to calix[4]arenes using acid-
catalyzed `311' condensation with 2,6-bis(halogeno-
methyl)-4-substituted phenols. The structural similarity of
the calix[4]arenes to meso-unsubstituted porphyrinogens
prompted us to apply this methodology to the synthesis of
5 and its furan analog 6, and the results will be described
with full experimental details in this paper.
in guidebooks of chemistry and biology. Although porphine
is the most basic compound in the porphyrin chemistry and
it has been more than 60 years since its ®rst synthesis, its
1
preparation is still one of the most dif®cult processes in
2
3
organic synthesis. In the previous letter, we described a
route to porphine using the `311' condensation of 2,5-
bis(hydroxymethyl)pyrrole (1) with newly acquired tri-
pyrrane (3) in 31% yield. This approach has been adopted
by Sakata et al. for the synthesis of a squared p-conjugated
4
porphyrin tetramer.
2
. Results and discussion
In general, the precursor porphyrinogen is readily oxidized
into the corresponding porphyrin with oxidizing agents such
as chloranil. However, the simplest porphyrinogen (5), to
the best of our knowledge, has not been isolated yet. Fully
meso-substituted porphyrinogens are stable, and the octa-5
methyl derivative was isolated back in 1886 by Baeyer.
2
.1. Formation of 2,5-bis(hydroxymethyl)pyrrole (1)
2
-(Hydroxymethyl)pyrrole is a quite attractive compound
for preparing porphyrinogen (5). In fact, Longo et al.
obtained porphine (8±10%), an oxidation product of 5, in
a reaction of the 2-(hydroxymethyl)pyrrole over a period of
Although the chemistry of fully meso-substituted por-6
phyrinogens has been extensively studied by Sessler et al.
1
0
10 days in chromatographed ethylbenzene at 1008C.
7
and Floriani et al. in recent years, that of b-substituted and
However, the compound is very hard to handle and to
store for a long period of time because of the occurrence
of self-condensation. 2-(Hydroxymethyl)pyrrole was
obtained from pyrrole by two steps, formylation of pyrrole
followed by reduction of the resulting pyrrolecarboxalde-
meso-unsubstituted porphyrinogens has remained unex-8
plored since Fischer and Baumler's ®rst isolation in 1929.
9
In 1979, K aÈ mmerer et al. reported a route to the methylene
1
1
hyde. An attempt to obtain 2-(hydroxymethyl)pyrrole by a
direct method was unsuccessful. In aqueous solution, under
the conditions of equimolar pyrrole and formalin, only
pyrrole and 1 were detected by MS measurement without
the desired compound.
Keywords: tripyrrane; porphyrinogen; porphyrin; 21-oxaporphyrinogen;
`
311' type condensation.
Corresponding author. Tel.: 181-29-271-2981; fax: 181-29-271-2992;
e-mail: taniguti@chem.ibaraki-ct.ac.jp
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00059-X

2
104
S. Taniguchi et al. / Tetrahedron 57 (2001) 2103±2108
with a rotary evaporator. The compound 1 is stable even at
08C in an alkaline solution under reduced pressure.
5
Acetone was added to the resulting white tacky solid, and
K CO was ®ltered off. The acetone solution was kept over
Na SO overnight to achieve complete dryness. Allowing
2
3
2
4
Scheme 1. Synthesis of 2,5-bis(hydroxymethyl)pyrrole.
the solution to stand for more than one day, the work-up
process became dif®cult because of self-condensation. The
crude product was obtained by removing the solvent.
Washing the white solid formed in a freezer with a mini-
mum amount of cooled acetone afforded white precipitates
in 84±92% yield, and these can be used without further
puri®cation for the next step. An attempt to purify of 1 by
vacuum distillation was unsuccessful because of decompo-
sition.
We then examined preparation of 1 from pyrrole under
various conditions of condensation according to the litera-
1
2
ture. Acid-catalyzed condensation by hydrochloric acid or
acetic acid afforded a black polymer or intractable tar.
Homogeneous, base-catalyzed condensation in ethanol or
ethanol±water afforded linear and cyclic oligomers.
Usually, but not always, pyrrole at a high concentration in
formalin solution tends to condense readily to tar or a
polymer. As pyrrole slowly dissolves into aqueous solution
with the progress of the reaction, the heterogeneous con-
ditions seems to be well suited to this work-up process, in
which water plays a vital role to control the reaction. Since
we needed to obtain 1 in suf®ciently large quantity, we did
not examine a high-dilution technique in a homogeneous
solution.
2,5-Bis(hydroxymethyl)furan (2) was obtained by acid-
pyrolysis of sugar followed by reduction of the resulting
3-(hydroxymethyl)furancarboxaldehyde, according to the
1
3,14
literature.
2.2. Formation of tripyrrane (3) and 2,5-bis (2-pyrrolyl-
methyl)furan (4)
At a temperature above 508C, condensation of pyrrole with
2
As described above, pyrrolic alcohols readily condense with
pyrrole to oligomers and polymers in the presence of acid
above room temperature. By analogy of the methylene-
bridged trimer of phenols from 2,6-bis(hydroxymethyl)-4-
substituted phenols and excess phenols, we applied the
methodology to a pyrrole system instead of phenols
(Scheme 2).
equiv. of formalin in a K CO solution afforded yellow tar,
2 3
which solidi®ed to a black polymer within 2 days upon
exposure to the atmosphere. At room temperature, conden-
sation under the same condition afforded 1 (,30%) with
tacky liquid. In this case, it was very dif®cult to separate 1
from oligomers in the puri®cation process. A technique of
column chromatography on silica gel was not effective in
this separation. The problem of oligomerization was
solved by vigorously stirring the heterogeneous solution in
a refrigerator below 58C for 7 days (Scheme 1). The upper
layer of pyrrole disappeared within 3 days. After the
reaction had been completed, water was quickly removed
to dryness at a temperature below 508C in vacuo (3±4 Torr)
9
Due to the lability and high reactivity of 1, it afforded only
intractable tar above room temperature in the presence of
acid. In alcoholic solution, the condensation products were a
mixture of a dimer and a trimer. The dimer, dipyrrolyl-
1
5
methane, was already isolated by column chromatography
on silica gel in a basic medium.16 We found that the dimer
Scheme 2. Direct synthesis of tripyrrane analogs.
Figure 1. The FDMS spectra of the distillation residue (TFA-catalyzed) of 3 (left) and 4 (right). The peaks of 3 at m/z 146, 225, 304, 383, 462, 541, 620, 699
and 778 show linear dimer to decamer, and cyclic trimer and tetramer are observed at m/z 237 and 316, respectively. The peak of 4 at m/z 385 corresponds to
linear pentamer (pyrrole 3, furan 2).

S. Taniguchi et al. / Tetrahedron 57 (2001) 2103±2108
2105
Scheme 3. Porphyrinogen synthesis by `311' condensation.
could be easily puri®ed by distillation at 107±1128C/
0.1 Torr. The tri¯uoroacetic acid-catalyzed condensation
of 1 with excess pyrrole was found to be quite effective,
but always accompanied by a small amount of the dimer.
Finally, we found that hydrochloric acid-catalyzed conden-
sation in water at low temperature gave 3 in the best yield
usefulness of the newly acquired unsubstituted tripyrrane
analogs, the synthesis of 5 by the `311' method was carried
out in the concentration of a 10 mM scale (Scheme 3). As
porphyrinogen is easily oxidized to porphyrin and is very
1
7
dif®cult to handle, except for calixpyrroles, we examined
the condensation in a 10-fold higher concentration as
compared to porphine synthesis. Thus, 5 was isolated for
(61%). These results mean that water is the best solvent and
it prefers a polar-protic solvent in this condensation.
1
the ®rst time in 14% yield. In the H NMR spectra of 5 in
CDCl3 at room temperature, meso-methylene protons
appeared at d 3.82 as a sharp singlet, and pyrrolic protons
appeared in an ordinary ®eld (d 7.38). This fact suggest that
the conformational inversion of the unsubstituted por-
phyrinogen 5 occurs rapidly in a chloroform solution at
room temperature. An attempt to collect X-ray diffraction
data was unsuccessful because of the unsuitable single
crystals from diethyl ether solution. In spite of an unstable3
compound, the difference of reactivity between the sp
Although the acid-catalyzed condensation of 1,3-bis-
(
hydroxymethyl)benzene or 2,6-bis(hydroxymethyl)pyri-
dine with excess pyrrole was unsuccessful, 2,5-bis(2-pyrro-
lylmethyl)furan (4) (58%) was obtained upon re¯ux for 1 h
from 2 and pyrrole in a similar manner. The distillate was
pale yellow viscous liquid with greenish ¯uorescence and
quickly solidi®ed. Vacuum distillation of 3 (TFA-catalyzed)
and 4 left a small amount of residue, in each case. The
FDMS spectra of the residues are shown in Fig. 1. A linear
dimer to decamer and the cyclic trimer and tetramer seem to
exist in the residue of 3. In contrast to 3, a linear pentamer
2
carbons (meso-positions) and the sp carbons (b-positions)
in 5 is of particular interest. Methylation of 5 with excess
CH I in the presence of AlCl afforded a reaction mixture of
3
3
(
pyrrole 3, furan 2) was observed as the main peak in the
mono- to octamethyl porphyrinogens. However, the isolated
products were so slight that we could not determine the
reaction positions.
residue of 4. These observation and the reaction temperature
indicate that 3 is more labile than 4.
2
2
.3. Formation of porphyrinogen (5) and
1-oxaporphyrinogen (6)
A sample of 4 was treated in the same manner as that of 3,
affording 6 (11% yield). In the H NMR spectra of 6 in
1
CDCl3 at room temperature, meso-methylene protons
connected with a pyrrole ring and connected with a furan
ring appeared at d 3.79 and d 3.86 as a sharp singlet, respec-
tively. This fact also suggests that the conformational inver-
sion of the unsubstituted 21-oxaporphyrinogen 6 occurs
rapidly in a chloroform solution at room temperature. The
structure of 6 in the solid state was con®rmed by X-ray
analysis as shown in Fig. 2. The results of analysis revealed
Recently, we recorded a good yield (31%) on porphine
synthesis in 1 mM condition. In order to demonstrate the
3
1
8
that 6 adopts a 1,2-alternated conformation and that rings
of the opposite side is approximately parallel to each other.
Sessler et al. reported that in the solid state meso-octa-
methylcalix[4]pyrrole and meso-tetraspirocyclohexylca-
1
7,19
lix[4]pyrrole adopt a 1,3-alternated conformation,
b-octabromo-meso-octamethylcalix[4]pyrrole adopts a ¯at-
but
2
0
tened 1,2-alternated conformation. Recently, Uno et al.
reported that fully b-substituted, meso-unsubstituted
porphyrinogen containing 2-propanol in the solid state
21
also adopts an ideal 1,2-alternate structure in the solid state.
The condensation of 2 with 3 seems to be another route to 6.
In fact, the reaction afforded a very small amount of 6. It
could be detect only on TLC but not isolated. An attempt to
obtain 21-oxaporphine by oxidation of 6 was carried out.
After the reaction had been completed, chloranil was
directly added to the solution, which was re¯uxed for
30 min and concentrated. The FDMS spectrum is shown
Figure 2. View of the molecular structure of 6. Thermal ellipsoids are
scaled to the 50% probability level. The compound adopts a 1,2-alternated
conformation in the solid state. Dihedral angles between least-squares
planes: O plane±N1 plane, 68.88; N1 plane±N2 plane, 70.78; N2 plane±
N3 plane, 72.08; O plane±N2 plane, 2.48; N1 plane±N3 plane, 2.48.

2
106
S. Taniguchi et al. / Tetrahedron 57 (2001) 2103±2108
Figure 3. FDMS spectrum of the oxidation mixture of one-pot synthesis: reaction of 4 with 6.
in Fig. 3. No peak corresponding to 21-oxaporphine (311 m/z)
was observed, and the intense peak at m/z 542 was tentatively
assigned to the product of Diels±Alder reaction of 4 with 6.
4.1.1. 2,5-Bis(hydroxymethyl)pyrrole (1). We improved
1
2
the reported method as follows. An aqueous solution
(200 mL) of potassium carbonate (62 g, 485 mmol) was
degassed by bubbling with argon for 30 min below 58C,
then 35% formalin (41.6 g, 485 mmol) was added. To the
cooled solution, pyrrole (16.4 g, 240 mmol) was imme-
diately added, then the solution was vigorously stirred for
5±7 days in a refrigerator at 58C. The upper layer of pyrrole
disappeared in 2±3 days. The solution was evaporated to
dryness below 508C under reduced pressure. Fresh acetone
(500 mL) was added to the resulting white viscous slurry.
The precipitated potassium carbonate was ®ltered off and
washed with acetone (2£300 mL), and the combined
organic solution was refrigerated overnight over Na SO
2 4
3
. Conclusions
The most basic unsubstituted porphyrinogen and unsubsti-
tuted 21-oxaporphyrinogen were isolated for the ®rst time in
the yield of 14 and 11%, respectively, by new building
blocks, 2,5-bis(hydroxymethyl)pyrrole and tripyrranes. 21-
Oxaporphyrinogen adopts a 1,2-altenated conformation in
the solid state. This new synthesis of tripyrranes would
contribute to the chemistry of porphyrins, core-modi®ed
porphyrins and expanded porphyrins.
(300 g). Evaporation of the solvent under reduced pressure
below 308C left a colorless viscous oil, which sometimes
solidi®ed during vacuum drying. A few milligrams of the
desired powders was added to the oil, then the oil was
cooled at 2208C in a freezer for 2 days, yielding a tacky
white solid. This solid was washed with ef®ciently cooled
acetone (20 mL) or 2-propanol (20 mL), giving a white
solid, which was collected by ®ltration to give 1 (25.6±
28.0 g, 84±92%). Can be stored for over ®ve years at
4
. Experimental
4.1. General
Melting points were determined with a SHIBATA 5227-01
and are uncorrected. IR spectra (JASCO FTIR-230) and H
1
1
2
NMR spectra (HITACHI R-1900 and JEOL GSX 400) were
recorded routinely. Mass spectra were taken on a HITACHI
M-70 or a JEOL JMS DX-300. FDMS was taken on a
HITACHI M-2000 equipped with a carbon emitter (acetone)
at the HITACHI CHEMICAL. X-ray diffraction data were
collected on a RIGAKU AFC7R diffractometer with
graphite monochromated Mo Ka. The structure was
typically solved by direct methods (SIR92). Elemental
analyses were performed with a YANACO CHN-CODER
MT-5. HPLC-analyses were performed on a HITACHI
2208C in a freezer, mp 115±1168C (dec., acetone, lit.
117±1188C). TLC: R
ˆ0.38 (silica gel, ethanol). HPLC:
f
2
R
50:50, 1 mL/min). H NMR (90 MHz, acetone-d
ˆ0.74 min (Inertsil ODS-2, 100£4 mm , CH
CN/H
O
): d 3.79
t
3
2
1
6
(br, 2H, OH), 4.48 (s, 4H, CH ), 5.84 (s, 2H, 3-H), 9.70
2
1
(br, 1H, NH). Ms: m/z 127 (M , 54), 110 (46), 96 (14),
2
1
80 (100), 53 (14). FTIR (KBr, cm ) 3304, 3250, 2938,
2869, 1425, 1203, 1027, 775. Anal. calcd for C NO :
2
H
6
9
C, 56.68; H, 7.13; N, 11.02. Found: C, 56.85; H, 7.21; N,
10.90.
655A-12 connected to a HITACHI 655A UV-monitor. As
columns, GASKUROKOGYO Inertsils (ODS-2, 100£
4.1.2. 2,5-Bis(2-pyrrolylmethyl)pyrrole (tripyrrane) (3).
Pyrrole (26.4 g, 394 mmol) was added to a stirred solution
of 1 (5.0 g, 39 mmol) in water (700 mL) below 58C under
argon with shielding from light. After 30 min, concentrated
hydrochloric acid (0.5 mL, 6 mmol) was added to the
ef®ciently stirred solution. The solution immediately chan-
ged to a white emulsion. After 30 min, the mixture was
2
2
4
mm or ODS, 150£4 mm ) were used with eluent, aceto-
nitrile/water 50:50. TLC was measured on KODAK
CHROMAGRAM sheet, #13181 silica gel.
Pyrrole and acetone were distilled before use. All other
chemicals were purchased in reagent quality and used as
received. All processes and reactions were carried out
under argon with shielding from light. 2,5-Bis(hydroxy-
methyl)furan (2) was prepared according to the literature
neutralized with aqueous NaHCO
pyrrole were removed in vacuo (3±4 Torr) with a rotary
evaporator, the residue was extracted with Et O or CH Cl
(3£300 mL), and the extract was subjected to distillation to
, water and excess
3
2
2
2
1
3,14
methods by two steps from sugar.

S. Taniguchi et al. / Tetrahedron 57 (2001) 2103±2108
2107
give 3 (5.4 g, 61%). Instead of the distillation, the separation
4.1.5. 21-Oxaporphyrinogen (21-oxa-hexahydroporphine)
(6). A sample of 4 (0.452 g, 2 mmol) was treated identically
as for 5, affording 72 mg (11%) of colorless needles. The
single crystals were prepared in diethyl ether. Mp 1578C
(dec., acetone). TLC: R ˆ0.87 (silica gel, CH Cl ). HPLC:
2
by column chromatography (300£20 mm ) on silica gel
using CH Cl as an eluent afforded 3 in 41% yield. Must
2
2
be stored in a freezer. A colorless solid, mp 97±988C (bp
1
86±1948C/0.1 Torr). TLC: R ˆ0.90 (silica gel, CH Cl ).
f
2
2
f
2
2
2
1
2
1
HPLC: R ˆ5.15 min (Inertsil ODS, 150£4 mm ). H NMR
R ˆ6.02 min (Inertsil ODS-2, 100£4 mm ). H NMR
t
t
(
90 MHz, CDCl ): d 3.74 (s, 4H, 5,10-H), 5.86 (d, 2H, Jˆ
(90 MHz, CDCl ): d 3.79 (s, 4H, 10-, 15-H), 3.86 (s, 4H,
3
3
2.4 Hz, 7-, 8-H), 5.93 (m, 2H, 3-, 12-H), 6.07 (m, 2H, 2-, 13-
H), 6.50 (m, 2H, 1-, 14-H), 7.36 (br, 1H, 16-NH), 7.64
(
5-, 20-H), 5.83 (s, 2H, 12-, 13-H), 5.86 (s, 2H, 8-, 17-H),
5.93 (s, 2H, 7-, 18-H), 5.97 (s, 2H, 2-, 3-H), 7.42 (br, 2H, 22-
, 24-NH), 7.52 (br, 1H, 23-NH). Ms: m/z 317 (M , 100), 172
1
br, 2H, 15-, 17-NH). Ms: m/z 225 (M , 100), 158 (52),
1
2
1
21
1
45 (71), 80 (74). FTIR (KBr, cm ): 3415, 3338, 3085,
898, 1097, 1026, 808, 800, 733, 725. Anal. calcd for
(22), 160 (48), 157 (32), 146 (23). FTIR (KBr, cm ): 3350,
2
C H N : C, 74.64; H, 6.71; N, 18.65. Found: C, 74.69;
H, 6.52; N, 18.82.
3337, 3128, 3105, 1563, 1182, 1113, 1091, 1028, 1012, 803,
765, 744, 738, 715, 566. Anal. calcd for C H N O: C,
75.69; H, 6.03; N, 13.24. Found: C, 75.46; H, 6.36; N, 13.03.
1
4
15
3
20 19
3
4
1
1
.1.3. 2,5-Bis(2-pyrrolylmethyl)furan (4). Pyrrole (7.0 g,
04 mmol) was added to a stirred solution of 2 (1.28 g,
0 mmol) in water (400 mL) at room temperature under
4.1.6. X-Ray structure of 21-oxaporphyrinogen (6).
Colorless crystals were grown slowly in a diethyl ether
solution in a refrigerator at 58C. The crystals were quickly
moved from a vial to a microscope slide in a steam of
argon. Under the microscope, a colorless plate (0.50£
argon with shielding from light. After 20 min, concentrated
hydrochloric acid (0.2 mL, 2 mmol) was added to the
ef®ciently stirred solution, and then the aqueous solution
was re¯uxed for 30 min. The mixture was cooled and
3
0.35£0.10 mm ) was selected and mounted on a glass
w
®ber using Aronalpha , and then coated with the bonding
neutralized with aqueous NaHCO , water and excess
3
agent. A total of 2694 re¯ections were collected in the u
range 3±308 of which 2470 were unique (Rintˆ0.035). The
structure was solved by direct method and expanded using
Fourier techniques. The non-hydrogen atoms were re®ned
anisotropically. The least-squares re®nement converged
normally with residuals of R (based on F)ˆ0.042, wR
pyrrole were removed in vacuo (3±4 Torr) with a rotary
evaporator, the residue was extracted with CH Cl2
2
(3£200 mL), and the extract was subjected to distillation
to give 4 (1.3 g, 58%). A pale yellow solid, mp 84±858C
(
bp 158±1608C/0.1 Torr). TLC: R ˆ0.95 (silica gel,
f
2
CH Cl ). HPLC: R ˆ3.46 min (Inertsil ODS-2, 100£
(based on F )ˆ0.044, and GOFˆ1.44 based upon
2
2
t
2
mm ). H NMR (90 MHz, CDCl ): d 3.95 (s, 4H, CH ),
1
4
5
6
1
3
1
I.3s(I). Crystal data for C20H N O: trigonal, space
19 3
3
2
0
.65 (m, 2H, 5 -H), 8.00 (br, 2H, NH). Ms: m/z 226 (M ,
0
Ê
Ê
.95 (s, 2H, 3-, 4-H), 6.00 (m, 2H, 3 -H), 6.13 (m, 2H, 4 -H),
0
groupˆR3 (#146), Zˆ8, aˆ20.225(4) A, cˆ10.762(6) A,
1
Ê
3
23
Vˆ3812(2) A , rcalcˆ1.106 g cm , F(000)ˆ1344. Atomic
coordinates, bond lengths and angles, and thermal
parameters for 6 have been deposited at the Cambridge
Crystallographic Data Center (CCDC).
2
1
00), 159 (49), 146 (78), 80 (47). FTIR (KBr, cm ): 3376,
351, 3336, 3129, 3105, 2886, 2830, 1563, 1182, 1113,
013, 802, 719, 708. Anal. calcd for C H N O: C, 74.31;
1
4
14
2
H, 6.24; N, 12.38. Found: C, 74.03; H, 6.31; N, 12.40.
4.1.4. Porphyrinogen (hexahydroporphine) (5). Com-
Acknowledgements
pound 3 (0.45 g, 2 mmol) was added to the stirred solvent
of chloroform (200 mL) previously degassed by bubbling
with argon at room temperature in a dark room. A solution
of 1 (0.254 g, 2 mmol) in methanol (5 mL) was added to the
stirred solution. After 20 min, 20% BF ´CH OH±methanol
We thank the Hitachi Chemical, for the FDMS measure-
ment. We also thank Dr Shouichi SATOH for helpful
discussion of X-ray structural analysis.
3
3
solution (227 mL, 0.4 mmol) was added with a micropipette,
and then the reaction mixture was stirred for 1 h. Further
stirring for 1 h was continued at 508C. Evaporation of the
solvent in vacuo left a viscous colorless oil. This oil was
dissolved in dichloromethane (10 mL), column chromato-
References
1. Fischer, H.; Gleim, W. Justus Liebigs Ann. Chem. 1935, 521,
157.
2
graphed (300£20 mm ) on silica gel using CH Cl as an
2. Neya, S.; Yodo, H.; Funasaki, N. J. Heterocycl. Chem. 1993,
30, 549.
2
2
eluent, and concentrated in vacuo to afford a colorless
solid. Recrystallization from acetone (5 mL) at 2208C
afforded 5 (86 mg, 14%). Attempt to collect the X-ray
diffraction data was not successful because of unsuitable
condition of single crystals from diethyl ether solution.
3. Taniguchi, S.; Hasegawa, H.; Nishimura, M.; Takahashi, M.
Synlett 1999, 73.
4. Sugiura, K.; Fujimoto, Y.; Sakata, Y. Chem. Commun. 2000,
1105.
Colorless needles, mp 1858C (dec., acetone). TLC: R ˆ
5. Baeyer, A. Chem. Ber. 1886, 19, 2184.
6. For example,Miyaji, H.; Anzenbacher Jr, P.; Sessler, J. L.;
Bleasdale, E. R.; Gale, P. A. Chem. Commun. 1999, 1723.
Gale, P. A.; Sessler, J. L.; Kr a l, V. Chem. Commun. 1998, 1
(and references cited therein).
f
0
.76 (silica gel, CH Cl ). HPLC: R ˆ7.83 min (Inertsil
2
2
t
2
1
ODS, 150£4 mm ). H NMR (90 MHz, CDCl ): d 3.82 (s,
3
8
H, CH ), 5.87 (d, 8H, Jˆ2.4 Hz, aromatic-H), 7.38 (br, 4H,
2
1
NH). Ms: m/z 316 (M , 100), 171 (20), 158 (40), 145 (10),
2
1
1
24 (12). FTIR (KBr, cm ): 3372, 3311, 3097, 3084, 2892,
882, 1413, 1302, 1039, 817, 806, 764, 753, 640. Anal.
7. For example, Bonomo, L.; Solari, E.; Scopelliti, R.; Floriani,
C.; Re, N. J. Am. Chem. Soc. 2000, 122, 5312. Floriani, C.
Chem. Commun. 1996, 1257 (and references cited therein).
8. Fischer, H.; Baumler, R. Ann. 1929, 468, 58.
2
calcd for C H N : C, 75.92; H, 6.37; N, 17.71. Found:
C, 76.02; H, 6.52; N, 17.54.
2
0
20
4

2
108
S. Taniguchi et al. / Tetrahedron 57 (2001) 2103±2108
9
. Happel, G.; Mathiasch, B.; K aÈ mmerer, H. Makromol. Chem.
975, 176, 3317. B oÈ hmer, V.; Chim, P.; K aÈ mmerer, H.
Makromol. Chem. 1979, 180, 2503.
15. Wang, Q. M.; Bruce, D. W. Synlett 1995, 1267.
1
16. Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427.
17. Gale, P. A.; Sessler, J. L.; Kr a l, V.; Lynch, V. J. Am. Chem.
Soc. 1996, 118, 5140.
1
1
1
0. Longo, F. R.; Thorne, E. J.; Adler, A. D.; Dym, S.
J. Heterocycl. Chem. 1975, 12, 1305.
18. Gutsche, D. D. Acc. Chem. Res. 1983, 16, 161.
19. Gale, P. A.; Sessler, J. L.; Kr a l, V. Chem. Commun. 1996,
1257.
1. Silverstein, R. M.; Ryskiewicz, E. E.; Chaikin, S. W. J. Am.
Chem. Soc. 1954, 76, 4485.
2. Tschelinzew, W. W.; Maxorow, B. W. Chem. Zentr. 1923, 1,
20. Gale, P. A.; Sessler, J. L.; Allen, W. E.; Tvermos, N. A.;
Lynch, V. Chem. Commun. 1997, 665.
1
505.
1
3. Harris, J. F.; Saeman, J. F. Forest Products J. 1960, 2, 125.
4. Ziegler, G. R. J. Am. Chem. Soc. 1969, 91, 446.
21. Uno, H.; Inoue, T.; Fumoto, Y.; Shiro, M.; Ono, N. J. Am.
Chem. Soc. 2000, 122, 6773.
1