A novel approach to the synthesis of mono- and dipyrroloporphyrins

Article abstract of DOI:10.1039/b108783p

A novel approach to the synthesis of mono- and dipyrroloporphyrins was discussed. The syntheses were based on a 1,5-electrocyclic ring closure followed by autoxidation of azomethine ylides, generated by the reaction of the nickel complexes of β-formylporphyrin derivatives with N-substituted glycines. A new product was formed with less reactive compounds along with the expected adducts. The structure of this new compound did not incorporate the dipolarophile used.

Full text of DOI:10.1039/b108783p

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A novel approach to the synthesis of mono- and
dipyrroloporphyrins
Ana M. G. Silva, Maria A. F. Faustino, Augusto C. Tomé, Maria G. P. M. S. Neves,
Artur M. S. Silva and José A. S. Cavaleiro*
1
Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Received (in Cambridge, UK) 27th September 2001, Accepted 28th September 2001
First published as an Advance Article on the web 10th October 2001
Starting with ꢀ-formyl- and ꢀ,ꢀЈ-diformylporphyrins, novel
mono- and dipyrroloporphyrins were synthesised via 1,5-
electrocyclization of porphyrinic azomethine ylides.
thesis of the metal-free forms of the hydro analogues of
compounds 3a and 6a via 1,3-dipolar cycloaddition reactions
of azomethine ylides to the peripheral double bonds of the
porphyrin macrocycle.4 Recently Smith et al. reported the first
synthesis of pyrrolo[3,4-b]porphyrins, based on the Barton–
Zard condensation of 2-nitro-5,10,15,20-tetraphenylporphyrin
with alkyl isocyanoacetates.5 By this method, the β-fused
pyrroloporphyrins are obtained as alkyl ester derivatives and
subsequent hydrolysis and decarboxylation are necessary to
afford the 2,5-unsubstituted pyrroloporphyrin 3c.
The first evidence for the formation of the pyrroloporphyrins
via the 1,5-electrocyclization of azomethine ylides 2 was
observed during our studies on the 1,3-dipolar cycloaddition
reactions of 2a to several dipolarophiles.6 We found that with
less reactive compounds, together with the expected adducts, a
new product was also being formed. Full spectroscopic charac-
The porphyrin macrocycle is known to display interesting prop-
erties. In order to extend or improve those properties, which
might be of great significance in the field of medicine or in the
production of new electronic materials, carbo- and heterocyclic
[b]fused porphyrins are being prepared.1
Here we describe a novel approach to the synthesis of
pyrrolo[3,4-b]porphyrins 3, dipyrrolo[3,4-b:3,4-g]porphyrins 6
and dipyrrolo[3,4-b:3,4-l]porphyrins 8 (Schemes 1–3).2 These
syntheses are based on a 1,5-electrocyclic ring closure,3 followed
by autoxidation, of azomethine ylides generated by the reaction
of the nickel complexes of β-formylporphyrin derivatives with
N-substituted glycines. Previously, we have described the syn-
Scheme 1
Scheme 2
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J. Chem. Soc., Perkin Trans. 1, 2001, 2752–2753
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b108783p

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Scheme 3
N. Kobayashi and H. Konami, J. Porphyrins Phthalocyanines,
terisation of this compound showed that it has the structure
3a.7 The structure of this new compound does not incorporate
the dipolarophile used. When the reaction of 1 with N-methyl-
glycine was carried out in the absence of a dipolarophile,
adduct 3a was obtained in 42% (Scheme 1). Later it was found
that better yields (55%) are obtained if potassium carbonate is
added to the reaction mixture.8 When the reaction was carried
out with N-benzylglycine hydrochloride and potassium carbon-
ate, pyrroloporphyrin 3b9 was isolated in 71% yield. Attempts
to synthesise compound 3c by reacting 1 with glycine, under
similar conditions, were unsuccessful.
2001, 5, 233; (c) T. D. Lash, in The Porphyrin Handbook, vol. 2,
eds. K. M. Kadish, K. M. Smith and R. Guilard, Academic Press,
San Diego, 2000, ch. 10, pp. 125–199.
2 Preliminary communication of this work: A. M. G. Silva, M. A. F.
Faustino, T. M. P. C. Silva, A. C. Tomé, M. G. P. M. S. Neves,
A. M. S. Silva and J. A. S. Cavaleiro, First International Conference
on Porphyrins and Phthalocyanines, POST 402, Dijon (France),
June, 2000.
3 (a) R. Huisgen, Angew. Chem., Int. Ed. Engl., 1980, 19, 947;
(b) E. C. Taylor and I. J. Turchi, Chem. Rev., 1979, 79, 181.
4 A. M. G. Silva, A. C. Tomé, M. G. P. M. S. Neves, A. M. S. Silva and
J. A. S. Cavaleiro, Chem. Commun., 1999, 1767.
These reactions were also extended to β,βЈ-diformyl deriva-
tives of meso-tetraphenylporphyrin (Schemes 2 and 3). Treat-
ment of each porphyrin derivative 4a–4c10 (with the formyl
groups in adjacent pyrrole rings) with N-methylglycine and
potassium carbonate afforded the adduct 6a in moderate to
good yields (40–72%). The highest yield was observed with
porphyrin 4b. When the progress of the reaction of 4b (and also
4c) with N-methylglycine was monitored by TLC, we observed,
in the early stages, the formation of two compounds: the inter-
mediate 5 (confirmed by MS) and the final product 6a. With
porphyrin 4a two isomeric intermediates 5 were observed.
When another similar reaction was carried out with a mixture
of the three isomers 4a–c, avoiding their separation by pre-
parative TLC, compound 6a was isolated in 43% yield. The
structure of this novel dipyrrolo derivative was unambiguously
established by spectroscopic data.11 Similar results were
obtained when a mixture of compounds 4a–4c was treated with
N-benzylglycine hydrochloride and potassium carbonate: the
expected adduct 6b was obtained in 42% yield.
When this type of reaction was carried out with a mixture
of compounds 4d and 4e (with the formyl groups in opposite
pyrrole rings) and N-methylglycine (in the absence of potas-
sium carbonate), the only product obtained was, unexpectedly,
the monopyrroloporphyrin 7 (13%). However, when the same
reaction was carried out in the presence of potassium carbonate
the product was the dipyrroloporphyrin 8 (36%). The structures
of compounds 7 and 8 were established by considering their
spectral data (NMR, MS and UV–Vis).12 Compound 8, in
contrast to compounds 6a and 6b, slowly decomposes in
chloroform solutions to yield highly polar products.
5 (a) L. Jaquinod, C. Gros, M. M. Olmstead, M. Antolovich
and K. M. Smith, Chem. Commun., 1996, 1475; (b) C. P. Gros,
L. Jaquinod, R. G. Khoury, M. M. Olmstead and K. M. Smith,
J. Porphyrins Phthalocyanines, 1997, 1, 201.
6 A. M. G. Silva, A. C. Tomé, M. G. P. M. S. Neves, A. M. S. Silva and
J. A. S. Cavaleiro, XIXth European Colloquium on Heterocyclic
Chemistry, p. 161, Aveiro (Portugal), July, 2000.
7 The spectroscopic data of product 3a are identical with those
reported in ref. 5b for the same compound (obtained as a by-product
during the decarboxylation of
porphyrin).
a 2-methoxycarbonylpyrrolo-
8 Typical procedure: a toluene (5 ml) solution of nickel() 2-formyl-
5,10,15,20-tetraphenylporphyrin (0.01 mmol), N-substituted
1
glycine (0.14 mmol) and potassium carbonate (0.07 mmol) was
refluxed for 16 h under a nitrogen atmosphere. New portions of N-
substituted glycine (0.14 mmol) and potassium carbonate (0.07
mmol) were added to the reaction mixture and reflux was continued
for another 8 h. After cooling to room temperature the carbonate
was filtered off and washed with dichloromethane. The resulting
solution was washed with water and dried (Na2SO4). After concen-
tration, the residue was purified by column chromatography (silica
gel) using a mixture of dichloromethane–light petroleum (3 : 7) as
eluent.
1
9 Spectroscopic data for 3b: H NMR (300 MHz, CDCl3) δ 5.20 (s,
2 H, CH2C6H5), 6.02 (s, 2 H, H-pyrrole), 7.07–7.10 and 7.36–7.38
(2 m, 5 H, CH2C6H5), 7.67–7.72 (m, 12 H, Hmeta para-Ph), 7.90–7.93
(m, 4 H, Hortho-Ph), 8.01–8.04 (m, 4 H, Hortho-Ph),ϩ8.577 (s, 2 H, H-12,
13), 8.578 (d, J 4.9, 2 H, H-β), 8.66 (d, J 4.9, 2 H, H-β); 13C NMR
(75 MHz, CDCl3) δ 54.1, 112.8, 112.9, 120.2, 126.8, 127.0, 127.5,
127.8, 128.0, 128.7, 128.8, 130.0, 131.0, 132.1, 132.5, 133.4, 137.3,
138.1, 139.6, 140.9, 141.8, 144.3; MS (LSIMS) 800 (M ϩ H)ϩ, 799
Mϩ; MS-HRFAB exact mass m/z for C53H35N5Ni (Mϩ ): calculated,
ؒ
799.2246, found 799.2246.
Attempts to obtain the metal free mono- and dipyrrolo-
porphyrins by starting from the corresponding demetallated β-
formylporphyrins or by demetallation of compounds 3a, b and
6a, b with H2SO4–CHCl3 (1 : 10) were unsuccessful. In both
cases only degradation products were obtained.
10 M. A. F. Faustino, T. M. P. C. Silva, A. M. G. Silva, M. G. P. M. S.
Neves, A. M. S. Silva, A. C. Tomé and J. A. S. Cavaleiro, XIXth
European Colloquium on Heterocyclic Chemistry, p. 96, Aveiro
(Portugal), July, 2000; A detailed description of the synthesis,
separation and characterisation of the five isomeric diformylpor-
phyrins 4a–4e is in preparation.
11 Spectroscopic data for 6a: 1H NMR (300 MHz, CDCl3) δ 3.72
(s, 6 H, 2 CH3), 5.80 (d, J 1.5, 2 H, H-pyrrole), 5.93 (d, J 1.5, 2 H,
Acknowledgements
H-pyrrole), 7.59–7.73 (m, 12 H, Hmeta para-Ph), 7.79–7.86 (m, 6 H,
ϩ
Hortho-Ph), 7.92–7.95 (m, 2 H, Hortho-Ph), 8.22 (d, J 4.7, 2 H, H-β),
Thanks are due to the University of Aveiro and to “Fundação
para a Ciência e a Tecnologia”, Portugal, for funding a PhD
grant (Ana M. G. Silva).
8.33 (d, J 4.7, 2 H, H-β); MS (LSIMS) 776 (Mϩ ); MS-HRFAB exact
ؒ
mass m/z for C50H35N6Ni (M ϩ H)ϩ: calculated, 777.2277, found
777.2279.
12 Spectroscopic data for 8: 1H NMR (300 MHz, CDCl3) δ 3.76 (s, 6 H,
2 CH3), 5.86 (s, 4 H, H-pyrrole), 7.61–7.70 (m, 12 H, Hmeta para-Ph),
ϩ
Notes and references
7.87–7.90 (m, 8 H, Hortho-Ph), 8.55 (s, 4 H, H-β); MS-HRFAB exact
mass m/z for C50H35N6Ni (M ϩ H)ϩ: calculated, 777.2277, found
777.2291.
1 (a) T. D. Lash, J. Porphyrins Phthalocyanines, 2001, 5, 267; (b)
J. Chem. Soc., Perkin Trans. 1, 2001, 2752–2753
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