Unusual phlorins from the oxidative coupling of pentapyrromethanes: Their facile conversion to meso-substituted porphyrins

Article abstract of DOI:10.1016/S0040-4039(01)00783-3

Direct, oxidant-mediated intramolecular coupling of pentapyrromethanes afforded 5-aryl-5-(2′-pyrryl)-10,15,20-triarylporphyrin (phlorins) as single products. The outcome of the reaction is comparable with the oxidative coupling of tetrapyrromethanes. Treatment of obtained phlorins with trifluoroacetic acid resulted in exclusive elimination of the peripheral pyrrole affording meso-tetraarylporphyrins quantitatively. The rate of pyrrole elimination depends on the acid concentration. The selective binding with fluoride anion was also observed with a large association constant.

Full text of DOI:10.1016/S0040-4039(01)00783-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4527–4529
Unusual phlorins from the oxidative coupling of
pentapyrromethanes: their facile conversion to
meso-substituted porphyrins
Jae-Won Ka and Chang-Hee Lee*
Institute of Basic Science and Department of Chemistry, Kangwon National University, Chun-Chon 200-701, South Korea
Received 27 March 2001; revised 18 April 2001; accepted 14 May 2001
Abstract—Direct, oxidant-mediated intramolecular coupling of pentapyrromethanes afforded 5-aryl-5-(2%-pyrryl)-10,15,20-triaryl-
porphyrin (phlorins) as single products. The outcome of the reaction is comparable with the oxidative coupling of tetra-
pyrromethanes. Treatment of obtained phlorins with trifluoroacetic acid resulted in exclusive elimination of the peripheral pyrrole
affording meso-tetraarylporphyrins quantitatively. The rate of pyrrole elimination depends on the acid concentration. The
selective binding with fluoride anion was also observed with a large association constant. © 2001 Published by Elsevier Science
Ltd.
Phlorins, the porphyrins bearing one sp3 hybridised
meso-carbon, have been known to be unstable and only
a few have been characterised so far.1 Due to the
air-sensitive nature of the compound, a bridging unit
between N(21) and N(22) or N-substituents was intro-
duced in some cases for the stabilisation of the com-
pounds.2 The protonation of phlorins under strongly
acidic conditions gave porphodimethenes, which could
be converted to the corresponding porphyrins by suc-
cessive oxidation.2 Conversion of dianionic Zn-TPP to
a Zn-porphodimethene and rearrangement to Zn-
(meso-tetraphenyl)chlorin has been demonstrated.3
More recently, Scott et al. demonstrated the reversible
conversion of porphyrin to porphodimethene.4 Geo-
metrically proximal nucleophiles to the meso-carbon
alter the electrochemical behaviour of reduced por-
phyrins and their system could be good models of a
molecular switch. The reaction of Ni(II)-porphyrins
with organolithium reagent has been reported to afford
the partially reduced porphyrins.5 All of these reduced
porphyrins are rather unstable due to the presence of
hydrogen at the meso-position. The reduced porphyrins
1 and 2 are tautomers, and so are 3 and normal
meso-tetraarylporphyrin, though the fully conjugated
forms are usually more stable due to aromatic
stabilisation.
In spite of their importance in redox chemistry and
biosynthetic pathway of porphyrins, the synthesis of
phlorins bearing different substituents other than
hydrogen at the sp3-carbon has not been documented.
This has been hampered by possible instability and
difficulties in placing the desired substituents. Reduc-
tion of one or more meso-carbons in the porphyrin
skeleton significantly alters the spectroscopic and elec-
tronic properties. The existence of different oxidation
Ar
H
Ar
Ar
H
H
H
H
N
N
H N
N H
N
N
N
Ar
H
Ar
Ar
Ar
Ar
Ar
N
N H
H N N H
N
H
Ar
Ar
Ar
3
1
2
Keywords: phlorin; reduced porphyrin; pentapyrromethane; oxidative coupling; molecular switch.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00783-3

4528
J.-W. Ka, C.-H. Lee / Tetrahedron Letters 42 (2001) 4527–4529
states, the [20p] system (1), which is a tautomeric form
of chlorin (2), and the fully oxidised [22p] system (3),
indicate the complexities of the molecules.
parable with similar oxidative coupling of tetra-
pyrromethanes, which resulted in the formation of
corroles exclusively.8 The absorption spectrum of 6
(R=H) showed a Soret-like band at 417 nm (m=2.4×
104) and an additional band at 680 nm (m=1.5×104).
The proton NMR spectra clearly showed the presence
of a mono-substituted pyrrolic moiety. Unlike por-
phyrin derivatives, a pyrrolic NꢀH signal was shown at
8.19 ppm as a broad singlet. The geometry of the
We have been studying the transformation of linear
oligopyrroles to porphyrinoid macrocycles ever since
the development of a single-step synthesis for oligo-
pyrromethanes.6 Direct and convenient access to the
functionalised porphyrins and corroles has been
achieved and we have demonstrated the advantages in
designing related model systems utilising oligopyrro-
methanes. The meso-aryl pentapyrromethanes 4 were
routinely isolated by column chromatography from the
dipyrromethane synthesis.6 The oxidative coupling of
pentapyrromethanes 4 was expected to afford sap-
phyrins 5, as shown in Scheme 1. But treatment of 4
with DDQ (3 equiv.) in acetonitrile unexpectedly
afforded 1-(pyrrol-2%-yl-1-aryl)-5,10,15-triarylporphyrin
(a porphyrin bearing one sp3 hybridised meso-carbon) 6
in 22% yield. The fast-moving dark green pigment was
isolated first by silica column chromatography followed
by compound 6. We provisionally assigned the fast-
moving green pigment as linearly oxidised pentapyrrolic
compounds.7
eastern-half of the compound
6
resembles the
calix[4]pyrrole and the western-half of the molecule
may adapt a dipyrromethene-like conformation.9 The
bright green coloured compound 6 was stable in air for
a prolonged period of time but the solution (CHCl3)
seems to be photosensitive and slow decomposition was
observed.10
Quantitative conversion of 6 to porphyrin 7 was accom-
plished by treatment with excess trifluoroacetic acid in
chloroform at room temperature (Scheme 1). Exclusive
elimination of the meso-substituted pyrrole was
observed. Preferable elimination of the pyrrolic moiety
over phenyl can be explained by the fact that C(2)-pro-
tonation in the pyrrole is more favourable than in the
phenyl group due to the electron-rich nature of pyrrole.
The product was also easily characterised by NMR and
mass spectroscopy. The progress of pyrrole elimination
was monitored by UV–vis spectroscopy (Fig. 1). The
The formation of tetrapyrrolic macrocycles seems to be
more favourable over the formation of pentapyrrolic
macrocycles (sapphyrinogen). These results are com-
R
R
R
R
N
H
N
H
[OX]
HN
NH
N
N
HN
NH
R
R
HN
NH
R
R
4
5
R = H, Me, OMe
DDQ
R
R
N H
N
H N
N
H N
TFA
R
H N N H
R
R
N
N H
R
R
R
7 (R=H)
6 (R=H)
Scheme 1.

J.-W. Ka, C.-H. Lee / Tetrahedron Letters 42 (2001) 4527–4529
4529
Figure 1. Time-dependent change in the UV–vis spectra of protonated 6 (2.65×10−5 M in CHCl3) upon treatment with TFA
(8.09×10−3 M). The arrows indicate the direction of changes. Each spectra was taken at 5 min intervals. Trace A: free base 6.
References
acid-catalysed elimination reaction showed simple
first-order kinetics and the observed pseudo first-order
rate constant calculated from Fig. 1 was 0.14/min.
The reaction rate was dependent on the acid concen-
tration.
1. (a) Setsune, J.; Yamaji, H.; Kaito, T. Tetrahedron Lett.
1990, 31, 5057–5060; (b) Setsune, J.; Ikeda, M.; Iida, T.;
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Am. Chem. Soc. 2000, 122, 10476–10477.
The preliminary binding behaviour of
6 toward
fluoride anions was studied using UV–vis spec-
troscopy. In the absence of anions, 6 is characterised
by a deep green colour. Upon gradual addition of F−,
the colour becomes yellowish. This colour change
occurs exclusively with F− and no detectable colour
change is observed with other halogen anions (Cl−,
Br− and I−). The calculated association constants for
fluoride were 3.4×104 and 1.2×105 M−1 and the Job
plot indicated a 1:2 binding ratio.
5. Senge, M. O.; Kalish, W. W.; Bischoff, I. Chem. Eur. J.
2000, 6, 2721–2738.
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7. The FAB-MS (MW 681.28) and proton NMR spectra
correspond to the mixture of linearly oxidised tetra-
pyrrolic pigments. Further isolation was not attempted at
this point.
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In summary, an easy conversion of porphotrimethene
(phlorin) to meso-substituted porphyrin under moder-
ate acidic conditions can be applied to the activation
of prodrugs. Development of photosensitisers acti-
vated after in vivo elimination of a certain group
would be a good example. Also, the reaction could be
applicable to the synthesis whenever the controlled
release of pyrrole is desired. It is also possible to
conceive the use of these elimination chemistry reac-
tions in sensing systems due to their dramatic change
in colour. Synthesis of other analogues and their pho-
tochemical- and anion-binding activities are under
intense investigation.
9. Bucher, C.; Seidel, D.; Lynch, V.; Kral, V.; Sessler, J. L.
Org. Lett. 2000, 2, 3103–3106.
10. A typical procedure for the coupling of 4: To a stirred
mixture of pentapyrromethane (4, 50 mg, 0.073 mmol)
and NH4Cl (38 mg, 0.73 mmol) in acetonitrile (36 mL)
was added DDQ (50 mg, 0.22 mmol). The mixture was
stirred for 1 h at room temperature and the solvent was
removed in vacuo. The remaining solid was purified by
column chromatography on silica (CH2Cl2). Yield: 11 mg
(22%, green solid). 1H NMR (CDCl3): l 5.86 (m, 1H,
pyrrolic-H), 6.18 (m, 1H, pyrrolic-H), 6.65 (d, J=3.9 Hz,
2H, pyrrolic-H), 6.78 (m, 1H, pyrrolic-H), 6.83 (d, J=3.9
Hz, 2H, pyrrolic-H), 6.87 (m, 2H, Ar-H), 6.94 (d, J=5.0
Hz, 2H, pyrrolic-H), 7.17 (m, 5H, pyrrolic-H+Ar-H),
7.41–7.49 (m, 9H, Ar-H), 7.57 (m, 2H, Ar-H), 7.65 (m,
4H, Ar-H), 8.19 (brs, NH). FAB-MS calcd for C48H35N5:
681.29; found: 681.96.
Acknowledgements
This work was supported by grants from the Korea
Science and Engineering Foundation (KOSEF grant
0100044-1-1). The NMR and MS data were obtained
from the Central Instrumental Facility at Kangwon
.
National University.