An inverted porphyrin with a pendant pyrrole - Identification of a tetraphenylsapphyrin isomer in the Rothemund synthesis

Article abstract of DOI:10.1016/S0040-4039(00)02190-0

2-Aza-3-(2′-pyrrolyl)-5,10,15,20-tetraphenyl-21-carbaporphyrin was identified among the products of a Rothemund synthesis and characterized. An alternative convenient method of its synthesis starting from 2-aza-5,10,15,20-tetraphenyl-21-carbaporphyrin was proposed.

Full text of DOI:10.1016/S0040-4039(00)02190-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1151–1154
An inverted porphyrin with a pendant pyrrole—identification of a
tetraphenylsapphyrin isomer in the Rothemund synthesis
Izabela Schmidt and Piotr J. Chmielewski*
Department of Chemistry, University of Wroc *l aw, F. Joliot-Curie 14, 50-383 Wroc *l aw, Poland
Received 17 November 2000; accepted 28 November 2000
Abstract—2-Aza-3-(2%-pyrrolyl)-5,10,15,20-tetraphenyl-21-carbaporphyrin was identified among the products of a Rothemund
synthesis and characterized. An alternative convenient method of its synthesis starting from 2-aza-5,10,15,20-tetraphenyl-21-carba-
porphyrin was proposed. © 2001 Elsevier Science Ltd. All rights reserved.
The Rothemund synthesis, i.e. the acid catalyzed con-
densation of pyrrole and an aryl aldehyde, has long
been used as an efficient source of tetraaryl porphyrins.
Only recently has it been shown that apart from the
porphyrin, other tetra- and pentapyrrolic aromatic
macrocycles can be isolated from the reaction mixture,
although in only minute yields.
tapyrrolic product of the Rothemund condensation,
namely 2-aza-3-(2%-pyrrolyl)-5,10,15,20-tetraphenyl-21-
carbaporphyrin 3, which, being an isomer of 2, belongs
to the newly emerging class of macrocycles identified by
the presence of a CH motif in the inner macrocyclic
perimeter.
1,2
3
Ph
Ph
Ph
Ph
H
Ph
Ph
24N
2
N
N
H
N
Ph
Ph
Ph
21
N
H
H
2’ N 1’
N23
H
N
H
H
N
H
H
H
N
H
N
N
N 22
5’
N
N
3’
N
H
N
H
4’
Ph
Ph
Ph
N
N
5-o
Ph
Ph
Ph
3
3a
1
2
Scheme 1.
Compound 3 has been identified among the products of
the condensation that had been carried out according
to the Lindsey protocol, although with an excess of
pyrrole with respect to benzaldehyde. In a typical syn-
thesis, condensation was carried out in degassed
dichloromethane with a pyrrole/benzaldehyde molar
The appropriate modifications of conditions can alter
the reaction pathway in such a way that one of these
compounds, i.e. 2-aza-5,10,15,20-tetraphenyl-21-carba-
4
porphyrin, an inverted porphyrin, an N-confused por-
phyrin 1, becomes the major product of condensation.
On the other hand, the yield of the only pentapyrrolic
macrocycle isolated to date from the Rothemund reac-
tion mixture, i.e. tetraphenyl sapphyrin, 2 has never
ratio of 1.5:1 and with pyrrole and BF etherate con-
3
centrations of 80 and 0.8 mM, respectively. After 1 h of
stirring at room temperature, p-chloranil (20 mM) was
added and the reaction mixture was refluxed for 1 h.
Chromatographic work-up and precipitation with hex-
5
exceeded one percent despite optimization efforts.
Here we report on the isolation, spectroscopic charac-
terization and tautomeric equilibrium of another pen-
6
ane gave a red–brown powder of 3 (yield 1.5%). Faster
moving bands contained mainly tetraphenylporphyrin
(
ca. 10%), 1 (5%) and 2 (ca. 1%). It seems that applica-
*
0
Corresponding author.
tion of an excess of pyrrole is crucial for the formation
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02190-0

1
152
I. Schmidt, P. J. Chmielewski / Tetrahedron Letters 42 (2001) 1151–1154
of 3 since no traces of this compound have been
observed when stoichiometric ratios of pyrrole and
benzaldehyde were used.
aging of chemical shifts of the ortho protons in non-pla-
nar porphyrin systems, i.e. rapid rotation of 5-phenyl,
can be excluded in this case considering the steric
overcrowding caused by closeness of the extraneous
pyrrole. The effective planar conformation of the sys-
tem can be combined with the internal hydrogen bond
formation between the nitrogen atoms of the bipyrrolic
fragment. The low-field position of the 1%-NH signal
(about 10 ppm) supports formation of such a bond
since the corresponding signal of free pyrrole appears at
7.70 ppm. The contribution from the porphyrin ring
current on the low-field shift of this proton can be
neglected because there is no analogous downfield shift
observed for other protons of the pendant pyrrole.
1
The H NMR spectrum of 3 (Fig. 1) shows a pattern
1
typical of inverted porphyrins with three upfield sig-
nals (21-CH, 22-NH, 24-NH) and three low-field AB
systems assigned to the b protons of the three pyrrole
rings. The most diagnostic spectral features of the
compound comprise a relatively broad low-field NH
peak and three signals in the region of 5.5–7 ppm
assigned to the protons of extraneous pyrrole based on
2
D COSY and NOESY techniques. The ortho protons
of the meso-phenyl in position 5 are represented by
only one H NMR signal in the temperature range
1
2
13–293 K showing their magnetic equivalence. The
The electronic spectrum of 3 in dichloromethane shows
3
degeneration of the phenyl protons indicates either a
planar conformation of the pentapyrrolic system or
porphyrin ring interconversion that is fast in the NMR
time scale. Another dynamic factor leading to the aver-
features typical of tetraphenyl sapphyrin rather than
1
an inverted porphyrin, which include relatively broad
bands located near 500 and 800 nm (Fig. 2). A similar
spectrum is observed for a pyridine solution, but it
3
-1’-NH 3a-1’-NH
3
a-2-NH
3
a-21
3
-21
3
a-pyrr
3a-(pyrr,Ph)
3
-22,24-NH
1
3
12
11
3
-(pyrr,Ph)
0
-2
-4
B
8
.5
8.0
7.5
7.0
1
’-NH
2
2,24-NH
21
pyrr + Ph
-o
Ph
1
0.5 10.0 9.5
pyrr
5
-
2
-4
5
’
4
’
3
’
A
9
.0
8.5
8.0
6.5 6.0 5.5
δ/ppm
1
Figure 1. 500 MHz H NMR spectrum of 3: (A) pyrrole and phenyl part of the spectrum of 3 at 293 K in CDCl , insets show
3
low- and high-field parts of the spectrum taken at 223 K in CDCl ; (B) central part and low- and high-field parts (insets) of the
3
spectrum at 253 K in DMF-d . Assignments: pyrr-b-pyrrole protons of porphyrin ring, Ph-meso-aryl protons. The other labels
7
follow those of Scheme 1.

I. Schmidt, P. J. Chmielewski / Tetrahedron Letters 42 (2001) 1151–1154
1153
50000
40000
30000
20000
10000
0
400
600
800
1000
λ /nm
Figure 2. Electronic spectra of 3 in dichloromethane (solid line) and in DMF (dashed line).
differs in DMF. This alteration is due to an equilibrium
between tautomers (Scheme 1). Similar tautomeric equi-
libria have been observed in polar solvents for 1 and
porphyrin was observed after 1 h. The yield after basic
alumina column chromatography (elution with CH Cl )
2
2
and hexane crystallization is 60%. Since 1 is now read-
7
4
inverted thia- and selenaporphyrins.
ily obtainable even on a gram scale the procedure
described is a promising synthetic method for 3
(Scheme 2).
1
H NMR in DMF-d confirms formation of 3a (the
7
3
:3a molar ratio is about 1:1 at 293 K) showing an
additional set of signals for which the most characteris-
tic is the one at 12.73 ppm (253 K) assigned to the
The reaction proceeds in DMF but not in chloroform,
dichloromethane, toluene or benzonitrile. Thus, during
the Rothemund condensation carried out in CH Cl ,
2
0
-NH being spin–spin coupled to the 21-CH proton at
2
2
.27 ppm (Fig. 1(B)). We found about 90% equilibrium
the macrocycle-pyrrole link must be formed prior to
oxidation of the inverted porphyrinogen. A pen-
tapyrrolic species containing a direct pyrroleꢀpyrrole
bond may be a ‘linear’ precursor of 2, 3 or 1 depending
on the way in which ring closure is accomplished. In
the latter case, however, a dissociation of the bipyrrolic
fragment is necessary after macrocyclic ring closure but
prior to oxidation.
1
shift to the right at 293 K in the case of 1 based on H
NMR measurements in DMF-d . Likely, the hydrogen
7
bond between the 1% and 2 nitrogen atoms disfavors
proton transfer from the inner to the outer perimeter of
the inverted porphyrin ring in 3.
1a
As in the case of 1, protonation of 3 with strong acids
+
proceeds in two steps giving (3-H)2 with the proton
+
attached to the position 2 and (3-H2) with all nitrogen
In conclusion, we have shown formation of a new
pentapyrrolic, aromatic product in the Rothemund syn-
thesis. The internal and external donor systems of 3 make
it attractive as a potentially bifunctional ligand possess-
ing macrocyclic and chelating or hydrogen-bonding
properties. The new type of reactivity of inverted pyrrole
of the N-confused porphyrin is noteworthy.
atoms protonated.
The very limited effectiveness of the Rothemund syn-
thesis with respect to 3 prompted us to look for an
alternative synthetic path since this compound seems to
be a very interesting macrocyclic/chelating ligand for
coordination of transition metal ions. We found that 3
can be more effectively obtained from a reaction of
inverted porphyrin 1 (50 mg, 0.08 mM) with a five-fold
excess of pyrrole in refluxing DMF (20 ml) containing
a catalytic amount of acid (0.01 mM BF OEt ). No
H
N
3
BF OEt2
1
+
3
DMF, reflux
3
2
additional oxidant is required if the reaction is con-
ducted in the presence of air. The full conversion of the
Scheme 2.

1
154
I. Schmidt, P. J. Chmielewski / Tetrahedron Letters 42 (2001) 1151–1154
Acknowledgements
Lett. 1999, 1, 1455.
. Geier, III, G. R.; Lindsey, J. S. J. Org. Chem. 1999, 64,
5
1596.
Financial support from the State Committee for Sci-
entific Research KBN of Poland is kindly acknowl-
edged.
6. Selected data for 3: umax (CH Cl )/nm (log m) 294 (4.16),
2
2
405 sh, 430 (4.66), 463 sh, 485 (4.67), 519 sh, 582 sh,
642 sh, 773 (3.71); lH (CDCl , 293 K) 9.64 (1H, b,
3
1
%-NH), 8.80 (1H, d, JAB=4.88 Hz), 8.69 (1H, d, JAB
=
4.88 Hz), 8.49 (2H, m, Hz, 5-o), 8.40 (2H, m), 8.39 (1H,
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