Novel Versatile Synthesis of Substituted Tetrabenzoporphyrins

Article abstract of DOI:10.1021/jo0350054

A novel general synthetic route to tetraaryltetrabenzoporphyrins (Ar ₄TBP) with various peripheral functional groups is developed. The procedure includes (i) Barton-Zard condensation of 1-nitro- or 1-phenylsulfonylcyclohexenes with isocyanoacet

Full text of DOI:10.1021/jo0350054

Novel Ver sa tile Syn th esis of Su bstitu ted Tetr a ben zop or p h yr in s
Olga S. Finikova,† Andrei V. Cheprakov,*,† Irina P. Beletskaya,† Patrick J . Carroll,‡ and
Sergei A. Vinogradov*,§
Department of Chemistry, Moscow State University, 119899 Moscow, Russia, Crystallographic
Laboratory, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
and Department of Biochemistry and Biophysics, University of Pennsylvania,
Philadelphia, Pennsylvania 19104
avchep@elorg.chem.msu.ru; vinograd@mail.med.upenn.edu
Received J uly 11, 2003
A novel general synthetic route to tetraaryltetrabenzoporphyrins (Ar4TBP) with various peripheral
functional groups is developed. The procedure includes (i) Barton-Zard condensation of 1-nitro- or
1-phenylsulfonylcyclohexenes with isocyanoacetic acid esters, (ii) condensation of the resulting
4,5,6,7-tetrahydroisoindoles with aromatic aldehydes to give fused tetraaryltetracylohexenopor-
phyrins (Ar4TCHP), and (iii) aromatization of the metal complexes of Ar4TCHP’s into the
corresponding Ar4TBP’s. Cu and Zn complexes of Ar4TBP’s are further demetalated to give the
corresponding Ar4TBP free bases. The overall yields for the sequence range from 15% to 40%, making
the method suitable for the preparation of gram quantities of Ar4TBP’s in a single run. The scope
of the method, the selection of the peripheral substituents, the choice of the metal ions, and their
influence on the yields of aromatization are discussed. The basic spectroscopic properties of newly
synthesized Ar4TBP’s and Ar4TCHP’s are reported together with the first X-ray crystallographic
structure of the NiAr4TBP complex.
In tr od u ction
phthalocyanines, partially retaining properties of both
and providing a useful point in structure/property com-
parative studies.
Tetrabenzoporphyrins have been studied substantially
more than other extended porphyrins. Their unique
photophysical,3 optoelectrochemical,4 and other physico-
chemical properties5 have attracted interest in different
Over the past decade interest in porphyrins fused with
external aromatic rings has been on the rise.1 Commonly
referred to as extended porphyrins,2 these macrocycles
possess interesting properties, inviting applications in
various branches of optical technology and biomedicine.
Tetraannulated porphyrins (tetrabenzoporphyrins, tet-
ranaphthaloporphyrins, etc.) and their metal complexes
form an especially intriguing class of extended porphy-
rins. Due to the higher order of their molecular sym-
metry, the spectral features of these compounds are much
sharper and better defined, and their absorption bands
are shifted considerably farther to the infrared.1d From
the structural point of view, the simplest representative
of this class, tetrabenzoporphyrin (TBP), is an intermedi-
ate between “regular” nonextended porphyrins and
(3) (a) Sevchenko, A. N.; Solovev, K. N.; Shkirman, S. F.; Kachura,
T. F. Dokl. Akad. Nauk SSSR 1965, 161, 1313 (Russian). (b) Bajema,
L.; Gouterman, M.; Rose, C. J . Mol. Spectrosc. 1971, 39, 421. (c)
Tsvirko, M. P.; Sapunov, V. V.; Soloviyev, K. N. Opt. Spektrosk. 1973,
34, 1094 (Russian). (d) Edwards, L.; Gouterman, M.; Rose, C. B. J .
Am. Chem. Soc. 1976, 98, 7638. (e) Koehorst, R. B. M.; Kleibeuker, J .
F.; Tjeerd, J . S.; de Bie, D. A.; Geursten, B.; Henrie, R. N.; van der
Plas, H. C. J . Chem. Soc. 1981, 1005. (f) Aartsma, T. J .; Gouterman,
M.; J ochum, C.; Kwiram, A. L.; Pepich, B. V.; Williams, L. D. J . Am.
Chem. Soc. 1982, 104, 6278. (g) Aaviksoo, J .; Frieberg, A.; Savikhin,
S.; Stelmakh, G. F.; Tsvirko, M. P. Chem. Phys. Lett. 1984, 111, 275.
(h) Dashkevich, S. N.; Kaliya, O. L.; Kopranenkov, V. N.; Luk’janets,
E. A. Zh. Prikl. Spektrosk. 1987, 47, 144 (Russian). (i) Ehrenberg, B.;
J ohnson, F. M. Spectrochim. Acta 1990, 46a, 1521 (j) Cheng, R. J .;
Chen, Y. R.; Chuang, C. E. Heterocycles 1992, 34, 1. (k) Vancott, T. C.;
Koralewski, M.; Metcalf, D. H.; Schatz, P. N.; Williamson, B. E. J . Phys.
Chem. 1993, 97, 7417. (l) Shkirman, S. F.; Gladkov, L. L.; Konstan-
tinova, V. K.; Solovyov, K. N. Spectrosc. Lett. 1998, 31, 1749. (m)
Nguyen, K. A.; Pachter, R. J . Chem. Phys. 2001, 114, 10757.
(4) (a) Vogler, A.; Rethwisch, B.; Kunkely, H.; Hutterman, J .;
Besenhard, J . O. Angew. Chem., Int. Ed. Engl. 1978, 17, 951. (b) Vogler,
A.; Kunkely, H. Inorg. Chim. Acta 1980, 44, L211. (c) Vogler, A.;
Kunkely, H.; Rethwisch, B. Inorg. Chim. Acta 1980, 46, 101. (d)
Martinsen, J .; Pace, L. J .; Phillips, T. E.; Hoffman, B. M.; Ibers, J . A.
J . Am. Chem. Soc. 1982, 104, 83. (e) Renner, M. W.; Cheng, R.-J .;
Chang, C. K.; Fajer, J . J . Phys. Chem. 1990, 94, 8508. (f) Madoka, Y.;
Tsiguo, Y.; Osami, O.; Kunihiro, I.; Hisayuki, M.; Masako, S. Inorg.
Chim. Acta 1991, 185, 39. (g) Liou, K. Y.; Newcomb, T. P.; Heagy, M.
D.; Thompson, J . A.; Heuer, W. B.; Musselman, R. L.; J acobsen, C. S.;
Hoffman, B. M.; Ibers, J . A. Inorg. Chem. 1992, 31, 4517. (h) Cheng,
R.-J .; Lin, S.-H.; Mo, H.-M. Organometallics 1997, 16, 2121. (i)
Plagemann, B.; Renge, I.; Renn, A.; Wild, U. P. J . Phys. Chem. A 1998,
102, 1725.
* Address correspondence to this author footnote.
† Moscow State University.
‡ Crystallographic Laboratory, Department of Chemistry, University
of Pennsylvania.
§ Department of Biochemistry and Biophysics, University of Penn-
sylvania.
(1) For review see: (a) Kobayashi, N. In Phthalocyanines. Properties
and applications; VCH Publishers: New York, 1993; Vol. 2. (b) Senge,
M. Highly substituted porphyrins. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New
York, 2000; Chapter 6. (c) Lash, T. D. Synthesis of novel porphyrinoid
chromophores. In The Porphyrin Handbook; Kadish, K. M., Smith, K.
M., Guilard, R., Eds.; Academic Press: New York, 2000; Chapter 10.
(d) Lash, T. D. J . Porphyrins Phthalocyanines 2001, 5, 267.
(2) Term extended refers to lateral π-conjugation, external to the
core porphyrin macrocycle. Extension of the macrocycle itself by adding
extra pyrrole moieties leads to expanded porphyrins (for review see:
Sessler, J . L.; Gebauer, A.; Vogel, E. Heteroporphyrins, expanded
porphyrins and related macrocycles. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New
York, 2000; Chapter 9).
10.1021/jo0350054 CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/20/2003
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J . Org. Chem. 2004, 69, 522-535

Synthesis of Tetrabenzoporphyrins
areas. For example, tetrabenzoporphyrins have been
considered as agents for PDT,6 optical limiters7 and other
types of nonlinear optical materials,8 luminescent mark-
ers for oxygen9 and pH10 in biomedical imaging, etc.
Nevertheless, compared to regular porphyrins and
phthalocyanines, the chemistry of tetrabenzoporphyrins
has been little investigated. The main reason for this has
been the lack of robust and general synthetic methods
leading to the tetrabenzoporphyrin system.
solubility. The latter obviously presented a serious
obstacle for the practical handling of TBP’s and hampered
the progress of their physicochemical studies. meso-
Tetraaryl-substituted tetrabenzoporphyrins (Ar4TBP), on
the other hand, turned out to be much more soluble and
better suited for practical work. The increased solubility
of Ar4TBP’s is probably at least in part caused by their
considerably nonplanar structures,5e,i which are due to
the steric crowding induced by four meso-aryl substitu-
ents.
Early approaches to the TBP system (for reviews, see
refs 1a,c) can be divided into two major groups. The first
group consists of the most straightforward attempts to
mimic the standard porphyrin synthesis, i.e., condensa-
tion of pyrroles with meso-carbon donors. To obtain
TBP’s, however, pyrroles have to be replaced by isoindole
or its derivatives,13 which in most cases are unstable and
not easily available.14
The second group of methods, which subsequently led
to a much wider array of TBP’s, stemmed from basic
phthalocyanine synthesis.3d,e,4c,12b In these methods the
meso-carbons in the porphyrin skeleton come not from
electrophilic carbonyls, as in traditional porphyrin con-
densations (Rothmund/Adler-Longo/Lindsey), but from
nucleophilic CH acids. As a result, unstable isoindoles
can be replaced by readily available phthalimides or their
derivatives. One version of this approach, developed by
Lukyanets and co-workers,15 appeared useful for the
synthesis of Ar4TBP’s. According to their method,
phthalimide is condensed with CH acids (e.g. arylacetic
acids) in the presence of metal salts, which are assumed
to serve as templates. Using 3-arylidenphthalimidines
instead of phthalimides was reported to give better yields
of Ar4TBP’s.15c However, the conditions required for the
condensation were so harsh (fusion at 350-400 °C) that
only inert substituents in the starting materials, such
as alkyl or halogen,9d,15,16 could sustain the procedure.
In addition, several studies3j,17a have demonstrated that
the high-temperature syntheses of Ar4TBP’s, via both the
isoindole13f and the phthalocylanie-type15b pathways, led
to the complex mixtures of porphyrins with one to four
meso-aryl substituents. Some minor improvements of the
method have been proposed,17b,18 but still low yields and
extremely laborious purifications made it quite impracti-
cal.
The first synthesis of tetrabenzoporphyrin, described
by Helberger11 and further developed in the works of
Linstead et al.,12 was inspired by the structural relation
of the tetrabenzoporphyrin macrocycle to both porphine
and phthalocyanine. Later data indeed revealed that the
plain unsubstituted TBP resembles its structural homo-
logues in a variety of ways, including extremely low
(5) (a) Hanack, M.; Zipplies, T. J . Am. Chem. Soc. 1985, 107, 6127.
(b) Remier, K. J .; Remier, M. M.; Still, M. J . Can. J . Chem. 1981, 59,
1388; (c) Yasuike, M.; Koseki, K.; Yamaoka, T.; Ichimura, K.; Sakuragi,
M.; Ohno, O. Inorg. Chim. Acta 1991, 183, 9. (d) Yasuike, M.; Shima,
M.; Koseki, K.; Yamaoka, T.; Sakuragi, M.; Ichimura, K. J . Photochem.
Photobiol. A-Chem. 1992, 64, 115. (e) Cheng, R. J .; Chen, Y. R.; Wang,
S. L.; Cheng, C. Y. Polyhedron 1993, 12, 1353. (f) Cheng, R. J .; Chen,
Y. R.; Chen, C. C. Heterocycles 1994, 38, 1465. (g) Carlson, J . B.;
Vouros, P. J . Mass Spectrosc. 1996, 31, 1403. (h) Bonnet, R.; Martinez,
G. J . Porphyrins Phthalocyanines 2000, 4, 544. (i) Finikova, O. S.;
Cheprakov, A. V.; Carroll, P. J .; Dalosto, S.; Vinogradov, S. A. Inorg.
Chem. 2002, 41, 6944.
(6) (a) Yasuike, M.; Yamaoka, T.; Ohno, O.; Sakuragi, M.; Ichimura,
K. Inorg. Chim. Acta 1991, 184, 191. (b) Lavi, A.; J ohnson, F. M.;
Ehrenberg, B. Chem. Phys. Lett. 1994, 231, 144. (c) Friedberg, J . S.;
Skema, C.; Baum, E. D.; Burdick, J .; Vinogradov, S. A.; Wilson, D. F.;
Horan, A. D.; Nachamkin, I. J . Antimicrob. Chemother. 2001, 48, 105.
(7) (a) Ambrose, W. P.; Moerner, W. E. Chem. Phys. 1990, 144, 71.
(b) Chen, P. L.; Tomov, I. V.; Dvornikov, A. S.; Nakashima, M.; Roach,
J . F.; Alabran, D. M.; Rentzepis, P. M. J . Phys. Chem. 1996, 100, 17507.
(c) Brunel, M.; Chaput, F.; Vinogradov, S. A.; Campagne, B.; Canva,
M.; Boilot, J . P. Chem. Phys. 1997, 218, 301. (d) Ono, N.; Ito, S.; Wu,
C. H.; Chen, C. H.; Wen, T. C. Chem. Phys. 2000, 262, 467.
(8) (a) Rao, D.; Aranda, F. J .; Roach, J . F.; Remy, D. E. Appl. Phys.
Lett. 1991, 58, 1241. (b) Rao, D. V.; Aranda, F. J .; Remy, D. E.; Roach,
J . F. Int. J . Nonlinear Opt. Prop. 1994, 3, 511. (c) Srinivas, N.; Rao, S.
V.; Rao, D.; Kimball, B. K.; Nakashima, M.; Decristofano, B. S.; Rao,
D. N. J . Porphyrins Phthalocyanines 2001, 5, 549. (d) Ohkuma, S.;
Yamashita, T. J . Photopolym. Sci. Technol. 2002, 15, 23. (e) Drobizhev,
M.; Karotki, A.; Kruk, M.; Rebane, A. Chem. Phys. Lett. 2002, 355,
175. (f) Karotki, A.; Drobizhev, M.; Kruk, M.; Spangler, C.; Nickel, E.;
Mamardashvili, N.; Rebane, A. J . Opt. Soc. Am. B-Opt. Phys. 2003,
20, 321.
(13) (a) Bender, C. O.; Bonnet, R.; Smith, R. G. J . Chem. Soc. 1969,
345. (b) Bender, C. O.; Bonnet, R.; Smith, R. G. J . Chem. Soc. 1970,
1251. (c) Bender, C. O.; Bonnet, R.; Smith, R. G. J . Chem. Soc. 1972,
771. (d) Bornstein, J .; Remy, D. E.; Shields, J . E. J . Chem. Soc. 1972,
1149. (e) Bornstein, J .; Remy, D. E.; Shields, J . E. Tetrahedron Lett.
1974, 4247. (f) Remy, D. E. Tetrahedron Lett. 1983, 24, 1452. (g)
Kopranenkov, V. N.; Makarova, Y. A.; Dashkevich, S. N. Khim.
Geterotsikl. Soedin. 1985, 10, 1372. (h) Bonnett, R.; McManus, K. A.
J . Chem. Soc., Perkin Trans. 1 1996, 2461. (i) Matsuzawa, Y.; Ichimura,
K.; Kudo, K. Inorg. Chim. Acta 1998, 277, 151.
(9) (a) Vinogradov, S. A.; Wilson, D. F. J . Chem. Soc., Perkin Trans.
2 1994, 103. (b) Vinogradov, S. A.; Lo, L.-W.; J enkins, W. T.; Evans,
S. M.; Koch, C.; Wilson, D. F. Biophys. J . 1996, 70, 1609. (c)
Vinogradov, S. A.; Wilson, D. F. Adv. Exp. Med. Biol. 1997, 411, 597.
(d) Rietveld, I. B.; Kim, E.; Vinogradov, S. A. Tetrahedron 2003, 59,
3821.
(10) Finikova, O.; Galkin, A.; Rozhkov, V.; Cordero, M.; Ha¨gerha¨ll,
C.; Vinogradov, S. J . Am. Chem. Soc. 2003, 125, 4882.
(11) (a) Helberger, J . H. J ustus Liebigs Ann. Chem. 1937, 529, 205.
(b) Helberger, J . H., von Rebay, A.; Hever, D. B. J ustus Liebigs Ann.
Chem. 1938, 533, 197. (c) Helberger, J . H.; Hever, D. B. J ustus Liebigs
Ann. Chem. 1938, 536, 173.
(14) Kovtunenko, V. A.; Voitenko, Z. V. Usp. Khim. 1994, 63, 1064
(Russian).
(15) (a) Kopranenkov, V. N.; Tarkhanova, E. A.; Lukyanets, E. A.
Zh. Org. Khim. 1979, 15, 642 (Russian). (b) Kopranenkov, V. N.;
Dashkevich, S. N.; Luk’yanets, E. A. Zh. Obshch. Khim. 1981, 51, 2165
(Russian). (c) Kopranenkov, V. N.; Makarova, E. A.; Lukyanets, E. A.
Zh. Obshch. Khim. 1981, 51, 2727 (Russian). (d) Kopranenkov, V. N.;
Makarova, Y. A.; Dashkevich, S. N. Khim. Geterotsikl. Soedin. 1985,
1372 (Russian). (e) Kopranenkov, V. N.; Makarova, E. A.; Dashkevich,
S. N.; Lukyanets, E. A. Khim. Geterotsikl. Soedin. 1988, 773 (Russian).
(16) (a) Ichimura, K.; Sakuragi, M.; Morii, H.; Yasuike, M.; Toba,
Y.; Fukui, M. Inorg. Chim. Acta 1991, 186, 95. (b) Vinogradov, S. A.;
Wilson, D. F. Tetrahedron Lett. 1998, 39, 8935.
(12) (a) Barret, P. A.; Linstead, R. P.; Rundall, F. G.; Tuey, G. A. P.
J . Chem. Soc. 1940, 1079. (b) Linstead, R. P.; Weiss, F. T. J . Chem.
Soc. 1950, 2975.
J . Org. Chem, Vol. 69, No. 2, 2004 523

Finikova et al.
SCHEME 1
the aromatization can be accomplished by using com-
monly available reagents, such as chloranil or DDQ.
There are a number of reports in the literature in
which aromatization by DDQ has been employed to
synthesize various asymmetrical extended porphyrins.20c,23
For example, both monobenzoporphyrin23a and diben-
zoporphyrin24 have been prepared by oxidative aromati-
zation with DDQ. Surprisingly, despite high interest in
fully symmetrical extended porphyrins, the idea of direct
oxidation of fused cyclohexene rings has never, to our
knowledge, been contemplated as a pathway to TBP’s.
Recently we began developing a synthetic scheme
leading to the TBP system, which relies on oxidative
aromatization of nonaromatized porphyrin precursors. In
an earlier communication we reported on the synthesis
of polysubstituted Ar4TBP’s by the oxidation of tetra-
cyclohexeno-fused porphyrins,25a and in a more recent
work a similar methodology was applied to the construc-
tion of further extended tetraaryltetra[2,3]naph-
thaloporphyrins (Ar4TNP).25b Herein we present a more
detailed account of this methodology, describing synthe-
ses of Ar4TBP’s with both substituted and unsubstituted
benzo rings. In addition, we present basic photophysical
properties of a few new tetrabenzoporphyrins and report
the first X-ray crystallographic structure of the NiAr4-
TBP complex.
The recent search for better synthetic routes to the
TBP system centered around “masked” isoindoles, i.e.,
c-annealated pyrroles. Such pyrroles, fused with non-
aromatic rings, are readily available via Barton-Zard
isocyanoacetate chemistry19 and appeared to be useful
synthones for other extended porphyrins.20 Two methods
based on this strategy were developed specifically for the
TBP system (Scheme 1).
In the method of Cavaleiro et al. (Scheme 1, step A),21
a sequence of reactions, including the modified Barton-
Zard synthesis, leads at first to an intermediate tetra-
cyclohexenoporphyrin, substituted with phenylsulfonyl
groups. This precursor porphyrin is then aromatized into
the TBP through base-catalyzed elimination of sulfinate,
succeeded by the oxidation of octahydrotetrabenzopor-
phyrin with DDQ (Scheme 1, step A). Another approach,
developed by Ono and co-workers,22 is based on the retro-
Diels-Alder extrusion of ethylene from porphyrins fused
with bicyclo[2.2.2]octadiene fragments (Scheme 1, step
B). The precursor pyrroles in this case are also synthe-
sized by using the Barton-Zard route. Although it relies
on a multistep reaction sequence and involves quite
complex intermediates, Ono’s method makes it possible
to obtain TBP’s in high purity and in virtually quantita-
tive yields at the last stage.
Resu lts a n d Discu ssion
Assuming that direct aromatization of the fused cy-
clohexene rings in tetracyclohexenoporphyrins (TCHP)
is possible, the retrosynthetic analysis of the TBP system
shown in Scheme 2 can be devised.
A feature shared by both of these methods is that the
aromatization requires the presence of a special “helper”
functionality, which is removed at the last stages of the
syntheses. An obvious drawback of this approach is that
the introduction of an additional group leads to an extra
synthetic effort. Moreover, it limits the choice of other
substituents, which are to be retained in the target
macrocycle. Avoiding the helper group by directly aro-
matizing fused cyclohexene rings would seem like a more
atom-economical and cost-effective method, especially if
The scheme consists of two parallel routes (1 and 2),
which are coupled via a set of similar Diels-Alder
reactions. These can be performed, in principle, at any
of the four stages, providing at least two pathways to each
of the key compounds. The most important advantage of
this scheme is very simple starting materials, i.e., Diels-
Alder adducts of butadiene with alkenes bearing groups
X. A large selection of such dienophiles is available,
allowing for a variety of substituents in the resulting
cyclohexene rings. Choosing symmetrically substituted
alkenes helps to avoid multiple randomers at the stage
of the macrocycle formation, although generally groups
X are not required to be the same.
The key intermediate of the entire sequence is 4,5,6,7-
tetrahydroisoindole ester (Route 2) and/or its Diels-
Alder-coupled analogue in Route 1. Both pyrroles can be
obtained via the modified Barton-Zard reaction, in which
arylsulfinate plays the role of the leaving group.26 The
arylsulfonyl variant of the Barton-Zard condensation
seems to be far more flexible than the original nitroolefin
(17) (a) Ichimura, K.; Sakuragi, M.; Morii, H.; Yasuike, M.; Fukui,
M.; Ohno, O. Inorg. Chim. Acta 1990, 176, 31. (b) Ichimura, K.;
Sakuragi, M.; Morii, H.; Yasuike, M.; Fukui, M.; Ohno, O. Inorg. Chim.
Acta 1991, 182, 83.
(18) (a) Galanin, N. E.; Kudrik, E. V.; Shaposhnikov, G. P. Russ. J .
Gen. Chem. 1999, 69, 1481. (b) Wang, D. Y.; Hu, M. X.; Hu, L. Z.; Zhao,
L. Z.; Lu, Z. Z.; Nie, Y. X.; Horie, K.; Machida, S. Mol. Cryst. Liq. Cryst.
Sci. Technol. A 1996, 291, 223. (c) Wang, X. Q.; Gao, S. A.; Cao, C. S.;
Shi, T. S.; Yu, L. X.; Cao, Z. X. Chem. J . Chin. Univ. 1996, 17, 843
(Chinese).
(19) (a) Barton, D.; Kervagoret, J .; Zard, S. Tetrahedron 1990, 46,
7587. (b) Barton, D.; Zard, S. J . Chem. Soc.. Chem. Commun. 1985,
1098.
(20) (a) Lash, T. D.; Novak, B. H. Tetrahedron Lett. 1995, 36, 4381.
(b) Lash, T. D.; Chandrasekar, P. J . Am. Chem. Soc. 1996, 118, 8767.
(c) Ono, N.; Hideo, H.; Ono, K.; Kaneko, S.; Murashima, T.; Ueda, T.;
Tsukamura, C.; Ogawa, T. J . Chem. Soc., Perkin. Trans. 1 1996, 417.
(d) Novak, B. H.; Lash, T. D. J . Org. Chem. 1998, 63, 3998. (e) Spence,
J . D.; Lash, T. D. J . Org. Chem. 2000, 65, 1530. (f) Lash, T. D.; Gandhi,
V. J . Org. Chem. 2000, 65, 8020.
(23) (a) Lash, T. D. Energy Fuels 1993, 7, 166. (b) Lash, T. D.; Roper,
T. J . Tetrahedron Lett. 1994, 35, 7715. (c) Lash, T. D.; Denny, C. P.
Tetrahedron 1995, 51, 59. (d) Tome, A. C.; Lacerda, P. S. S.; Neves,
M. G. P. M. S.; Cavaleiro, J . A. S. Chem. Commun. 1997, 1199.
(24) Nguyen, L. T.; Senge, O. M.; Smith, K. M. J . Org. Chem. 1996,
61, 998.
(25) (a) Finikova, O. S.; Cheprakov, A. V.; Beletskaya, I. P.;
Vinogradov, S. A. Chem. Commun. 2001, 261. (b) Finikova, O. S.;
Cheprakov, A. V.; Carroll, P. J .; Vinogradov, S. A. J . Org. Chem. 2003,
68, 7517.
(26) (a) Arnold, D. P.; Burgess-Dean, L.; Hubbard, J .; Abdur
Rahman, M. Aust. J . Chem. 1994, 47, 969. (b) Abel, Y.; Haake, E.;
Haake, G.; Schmidt, W.; Struve, D.; Walter, A.; Montforts, F. P. Helv.
Chim. Acta 1998, 81, 1978.
(21) Vicente, M. G. H.; Tome, A. C.; Walter, A.; Cavaleiro, J . A. S.
Tetrahedron Lett. 1997, 38, 3639.
(22) (a) Ito, S.; Murashima, T.; Uno, H.; Ono, N. Chem. Commun.
1998, 1661. (b) Ito, S.; Ochi, N.; Murashima, T.; Uno, H.; Ono, N.
Heterocycles 2000, 52, 399. (c) Ito, S.; Uno, H.; Murashima, T.; Ono,
N. Tetrahedron Lett. 2001, 42, 45. (d) Uno, H.; Ono, N. J . Synth. Org.
Chem. J pn. 2002, 60, 58. (e) Uno, H.; Ishikawa, T.; Hoshi, T.; Ono, N.
Tetrahedron Lett. 2003, 44, 5163.
524 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis of Tetrabenzoporphyrins
have been implemented previously,28b,30 but the target
TBP structure has never been obtained in this way.
A specific pathway, derived from the retrosynthetic
analysis outlined above (Route 2) and implemented in
this work is shown in Scheme 3.
SCHEME 2. Retr osyn th etic An a lysis of th e TBP
System a
The starting materials for the Barton-Zard condensa-
tion (step a), i.e., isocyanoacetic acid esters and cyclic
vinylsulfones (4), can be easily prepared from inexpensive
precursors or, in some cases, are available commercially.
In special cases, when no substituents X are needed in
the target macrocycles, the simplest choice of the starting
compound would be 1-nitrocyclohexene, available from
a number of commercial sources. Tetrahydroisoindole
esters 5, obtained from the Barton-Zard reaction, are
deesterified and decarboxylated (step b) into unsubsti-
tuted 4,5,6,7-tetrahydroisoindoles 6. These are further
reacted with aromatic aldehydes under Adler-Longo or
Lidsey conditions (step c) giving meso-tetraaryl tetra-
cyclohexenoporphyrins (Ar4TCHP, 7). The next step,
which is the key to the whole sequence, is the oxidative
aromatization (step d) of Ar4TCHP’s 7 into Ar4TBP’s 8.
As shown below, aromatization requires the presence of
metals in Ar4TCHP’s, and later the metal ions must be
removed to generate free base Ar4TBP’s. Thus, the choice
of metals is critical for the success of the synthesis.
A detailed discussion of the procedures involved in the
syntheses of two classes of Ar4TBP’s, i.e., with and
without substituents X, is presented below.
m eso-Tetr a a r yltetr a (4,5-d im eth oxyca r bon yl)ben -
zop or p h yr in s Ar 4TBP (CO2Me)8 (8a -e). Octamethoxy-
carbonyltetrabenzoporphyrins (Ar4TBP(CO2Me)8) and
octacarboxytetrabenzoporphyrins (Ar4TBP(CO2H)8) were
our initial synthetic targets. The latter porphyrins can
be easily modified by either esterification or coupling with
amines, allowing for control over their solubility in media
of different polarities. For example, Ar4TBP(CO2H)8 and
their PEG-ester derivatives are well soluble in water,
making it possible to study their basicity5i and evaluate
their efficacy in various biomedical applications,9,10,25
where high aqueous solubility is a necessary require-
ment. A route to Ar4TBP(CO2Me)8, developed in this
work, is depicted in Scheme 4.
The starting material for the Barton-Zard reaction is
cyclic vinylsulfone 4a . 4a was obtained from dimethyl
tetrahydrophthalate 2, whose cis isomer was prepared
from the commercially available adduct of butadiene and
maleic anhydride 1 (Scheme 4, a). The trans isomer of 2
was synthesized by the Diels-Alder reaction of dimethyl
maleate (DMM) with 1,3-butadiene (Scheme 4, c), pro-
duced by the thermal extrusion of SO2 from butadiene
sulfone 1 (sulfolene).31 Although from the standpoint of
the target materials both cis-2 and trans-2 are equally
well suited for the transformations to follow, in practice
using each isomer revealed certain advantages and
drawbacks (see below).
a
D-A denotes Diels-Alder reactions.
version. While synthesis of 1-nitrocyclohexenes is rather
inconvenient, the arylsulfonyl group can be easily placed
near almost any carbon-carbon double bond (Route 2),
using a reliable chlorosulfenylation-oxidation-elimina-
tion protocol,27 or addition-elimination reactions.28 In
addition, 1-arylsulfonylcyclohexenes can be prepared
through the Diels-Alder condensation from 2-arylsul-
fonylbutadiene (Route 1).29
The remaining elements of Scheme 2 are the depro-
tection of the pyrrole esters, the porphyrin synthesis
itself, and the aromatization. The first two processes are
very well documented and will be discussed below as they
apply to our particular case. The aromatization, on the
other hand, is a specific feature of the proposed scheme
and will be discussed separately (also see below). Finally,
it should be mentioned that some parts of the scheme
Compound 2 was further reacted with PhSCl (Scheme
4, b), succeeded by oxidation and elimination of HCl to
give vinyl sulfone 4a in a high yield (85%).27 As shown
in the scheme, 4a also could be synthesized by first
(27) Hopkins, P. B.; Fuchs, P. L. J . Org. Chem. 1978, 43, 1208.
(28) (a) Inomata, K.; Sasaoka, S.; Kobayashi, T.; Tanaka, Y.;
Igarashi, S.; Ohtani, T.; Kinoshita, H.; Kotake, H. Bull. Chem. Soc.
J pn. 1987, 60, 1767. (b) J ohnstone, K. D.; Pearce, W. A.; Pyke, S. M.
J . Porphyrins Phthalocyanines 2002, 6, 661-672.
(29) (a) Backvall, J . E.; J untunen, S. K. J . Am. Chem. Soc. 1987,
109, 6396. (b) Backvall, J . E.; Chinchilla, R.; Najera, C.; Yus, M. Chem.
Rev. 1998, 98, 2291. (c) Cheng, W. C.; Olmstead, M. M.; Kurth, M. J .
J . Org. Chem. 2001, 66, 5528.
(30) (a) Krautler, B.; Sheehan, C. S.; Rieder, A. Helv. Chim. Acta
2000, 83, 583. (b) Gunter, M. J .; Tang, H.; Warrener, R. N. J .
Porphyrins Phthalocyanines 2002, 6, 673.
(31) Chou, T. S.; Hung, S. C. J . Org. Chem. 1988, 53, 3020.
J . Org. Chem, Vol. 69, No. 2, 2004 525

Finikova et al.
SCHEME 3a
a
Reaction steps: (a) Barton-Zard condensation; (b) pyrrole-ester cleavage; (c) macrocycle assembly; (d) aromatization.
SCHEME 4a
a
Reagents and conditions: (a) MeOH, TosOH cat., reflux (95%); (b) (i) PhSCl, CH2Cl2, rt; (ii) MCPBA, CH2Cl2, rt; (iii)DBU (85% for 3
steps); (c) DMM, py, toluene, 180 °C, pressure tube (85%); (d) (i) PhSCl, CH2Cl2, rt; (ii) MCPBA, CH2Cl2, rt, or oxone, MeOH-water; (iii)
Et3N (86% for 3 steps); (e) DMM, py, toluene, 180 °C, pressure tube (54%); (f) CNCH2CO2R, tBuOK, THF, 0 °C (75-95%); (g) for R ) Bn:
(i) H2, Pearlman catalyst, THF-MeOH-Et3N, rt; (ii) (CH2OH)2, reflux, 30 min (85-90% for 2 steps); for R ) tBu: TFA-CH2Cl2, rt (30%);
(h) ArCHO, BF3‚Et2O, CH2Cl2, rt, 1.5-2 h, then DDQ, overnight (20-55%); (i) ArCHO, AcOH, TsOH, air, reflux, 8 h (11% for Y ) H); (j)
metal salt (90-98%; see text for conditions); (k) DDQ, THF or MeCN, reflux, 0.5-3 h (90-95%); (l) M ) Cu: (i) H2SO4 concentrated; (ii)
MeOH (95% for 8a -c, 5% for 8d ,e; yields are given for two steps).
transforming sulfolene 1a into its phenylsulfonyl deriva-
tive (Scheme 4, d), obtained usually as a mixture of
isomers 3 and 3a , and then condensing it with DMM
(Scheme 4, e). The yields of 4a recovered in this route
were, however, relatively low due to the dimerization of
2-phenylsulfonylbutadiene (30-40%).
Barton-Zard condensation of 4a with tert-butyl and
benzyl isocyanoacetates (Scheme 4, f) afforded the cor-
responding 4,5,6,7-tetrahydroisoindoles 5a ,b in 75-95%
yield. Using the cis isomer of 4a appeared advantageous,
since purification of the trans-pyrrole ester 5b was
complicated by the presence of two regioisomers. Origi-
nally, we focused on using tert-butyl derivative 5a , since
it seemed more convenient to transform the ester into
tetrahydroisoindole 6a by using a simple one-pot depro-
tection-decarboxylation procedure and treatment with
TFA (Scheme 4, g). The yields of 6a obtained in this way,
however, were quite low, 30-40%. On the other hand, a
two-stage procedure, beginning with benzyl ester 5b, was
found to be much more efficient, and cis-5b could be
obtained in a pure crystalline form. cis-5b was subjected
to hydrogenolysis, followed by decarboxylation of the
526 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis of Tetrabenzoporphyrins
resulting pyrrole carboxylic acid in refluxing ethylene
glycol, giving cis-6a in 85-90% overall yield. The com-
mercial Pd/C catalyst appeared ineffective in the ester
cleavage, while Pearlman’s catalyst,32 i.e., Pd(OH)2/C,
afforded quantitative conversion of 5b into the acid. The
Pearlman catalyst is known for its ability to perform well
in the cases where regular Pd/C catalysts fail.
driven to completion only in the presence of a base, e.g.
Et3N or K2CO3. Alternatively, Pd could be inserted by
refluxing a porphyrin with PdCl2 in benzonitrile, in which
case the base was not required and insertion occurred
much faster. Expectedly, Zn complexes of Ar4TCHP(CO2-
Me)8’s were found to be much more acid sensitive than
Cu, Ni, and Pd derivatives.
Octamethoxycarbonyltetracyclohexenoporphyrins Ar4-
TCHP(CO2Me)8 (7a -e) were synthesized in moderate to
high yields (25-55%) by condensation of tetrahydroiso-
indole 6a with aromatic aldehydes (Scheme 4, h) follow-
ing the standard Lindsey method.33 It is interesting that
in some cases an alternative “one-pot” Adler-Longo type
procedure (Scheme 4, i) could be implemented, in which
tert-butyl ester 5a reacted directly with aromatic alde-
hydes in the presence of TsOH. In these cases, pyrrole
6a was generated in situ. Although lower yields were
usually afforded (5-15%), this approach is still worth
consideration, since it essentially removes two stages
from the overall reaction sequence.
The next step of the sequence is the oxidative aroma-
tization of tetracyclohexenoporphyrins into tetraben-
zoporphyrins. Our initial discovery, however, was that
under no conditions could Ar4TCHP(CO2Me)8’s free bases
be aromatized into Ar4TBP(CO2Me)8’s by either p-chlo-
ranil or DDQ or any other oxidants available to us.
Apparently, Ar4TCHP(CO2Me)8’s taken as free bases
immediately formed the corresponding dications upon
addition of aromatizing agents. Consequently, no progress
in aromatization could be observed even after several
hours of refluxing Ar4TCHP(CO2Me)8’s with DDQ, mak-
ing it clear that porphyrin dications are totally inert in
oxidation.
The resulting Ar4TCHP(CO2Me)8’s (7a -e) were iso-
lated as bright green porphyrin dications (acetates of
chlorides). These dications formed instantly upon addi-
tion of DDQ (Lindsey method) causing a color change of
the solution to deep green. An important property of
porphyrins 7a -e is that their dications could be fully
deprotonated only in the presence of quite strong bases,
such as triethylamine or DBU. For example, a solution
of 7a in CH2Cl2/pyridine (3:1) still contained about 50%
of the dication, and even in pure pyridine about 10% of
the porphyrin remained protonated. Such behavior of Ar4-
TCHP(CO2Me)8’s is a result of their extremely high
basicity, which, as shown below, appeared to be an
important issue in the context of their conversion into
the corresponding TBP’s by oxidative aromatization.
The enhanced basicity of dodecasubstituted porphyrins
has been well documented in the literature.34 It is
typically associated with their severe nonplanarity, al-
though other factors affect it as well. In this respect, Ar4-
TCHP(CO2H)8’s present a unique model for systematic
studies of the factors influencing the basicity of the
porphyrin macrocycle. The presence of eight carboxylic
groups in these porphyrins ensures their excellent water
solubility and allows for accurate measurements of their
thermodynamic pK values.5i The latter are usually quite
hard to assess due to the intrinsic hydrophobicity of
porphyrins.
Metallo-Ar4TCHP(CO2Me)8’s (M-7a -e), on the other
hand, behaved completely differently. Porphyrinates of
metals with easily accessible high oxidation states, such
as Fe, Co, and Mn, refused aromatization, whereas
complexes of bivalent metals, such as Zn, Cu, Ni, and
Pd, could be readily oxidized into the corresponding
metallo-Ar4TBP(CO2Me)8’s (M-8a -e) upon refluxing in
acetonitrile with DDQ (Scheme 4, k). However, large
variations in stability made porphyrinates of the latter
metals quite different in terms of practical handling. It
appeared that more labile Zn complexes rapidly lost
metal under aromatization conditions, thus yielding
dications and causing incomplete conversions and low
yields. Although the target ZnAr4TBP(CO2Me)8’s and the
remaining starting Ar4TCHP(CO2Me)8’s always could be
recovered by column chromatography, the whole proce-
dure, involving intermediate separations, remetalations,
and repetitive oxidations, was laborious and cumbersome.
In contrast, aromatization of metalloporphyrins M-7a -e
(M ) Ni, Cu, Pd) resulted in nearly quantitative yields
and no metal loss could be detected. In the latter cases,
the aromatization usually took place in just a few
minutes, causing drastic color changes of the reaction
mixtures from characteristic red-brown (MAr4TCHP(CO2-
Me)8’s) to deep green (MAr4TBP(CO2Me)8’s). The presence
of electron-withdrawing groups in meso-aryl rings mark-
edly decreased the reaction rate. For example, aromati-
zation of Cu -7e (Y ) 4-NO2) required a prolonged
refluxing (2-3 h) in CH3CN, while oxidation of Cu -7a
(Y ) H) was complete after 15-20 min. Nevertheless, in
all the cases involving Ni, Cu, and Pd porphyrins,
oxidation could be driven to completion and gave excel-
lent yields of the target tetrabenzoporphyrins.
Subsequent aromatization of Ar4TCHP(CO2Me)8’s re-
quired their conversion into metal complexes (see below).
MAr4TCHP(CO2Me)8’s (M ) Zn, Ni, Cu, Pd) could be
easily prepared by reacting the free base porphyrins with
metal salts in appropriately chosen solvents (Scheme 4,
j). Zn, Cu, and Ni were inserted in CH2Cl2/MeOH (9:1)
under mild conditions, using the corresponding acetates,
while insertion of Pd required prolonged heating of
porphyrins with PdCl2 in MeCN/THF (1:1) and could be
Since the oxidative aromatization of tetracyclohex-
enoporphyrins35 into tetrabenzoporphyrins is central to
the described synthetic scheme, it is interesting to
consider possible mechanistic pathways for this trans-
formation. In our opinion, the most feasible mechanism
(32) Pearlman, W. M. Tetrahedron Lett. 1967, 1663.
(33) Lindsey, J . S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J . Org. Chem. 1987, 52, 827.
(34) (a) Medforth, C. J .; Berber, M. D.; Smith, K. M.; Shelnutt, J .
A. Tetrahedron Lett. 1990, 31, 3719. (b) Medforth, C. J .; Smith, K. M.
Tetrahedron Lett. 1990, 31, 5583. (c) Barkigia, K. M.; Berber, M. D.;
Fajer, J .; Medforth, C. J .; Renner, M. W.; Smith, K. M. J . Am. Chem.
Soc. 1990, 112, 8851. (d) Takeda, J .; Ohya, T.; Sato, M. Inorg. Chem.
1992, 31, 2877.
(35) In the following paragraphs, which deal with mechanistic
aspects of the oxidative aromatization, the term “tetracyclohexenopo-
rphyrins” refers to both octamethoxycarbonyl tetracyclohexenoporphy-
rins (Ar4TCHP(COMe)8) and benzo-unsubstituted tetracyclohexeno-
porphyrins (Ar4TCHP), introduced later in the text. The term “tetra-
benzoporphyrins” is used similarly.
J . Org. Chem, Vol. 69, No. 2, 2004 527

Finikova et al.
involves the single-electron transfer (SET) from the
metallo-Ar4TCHP to DDQ with the formation of an ion-
radical pair [MAr4TCHP+•/DDQ-•] at the first stage. The
semiquinone anion-radical DDQ-• further induces the
stepwise abstraction of a hydrogen atom and a proton,
with the net result of dehydrogenation. Alternatively, this
sequence can be presented as an abstraction of a hydride
from MAr4TCHP followed by the proton transfer, which
might be, in fact, indistinguishable from the stepwise
“fast” abstraction of the electron, “fast” transfer of the
hydrogen atom, and “slow” transfer of the proton. Oxida-
tions by DDQ are usually regarded within the framework
of the SET/hydride abstraction mechanistic dualism.36
It is interesting that the molecular complex between
tetraphenylporphyrin (H2TPP) and DDQ has been re-
ported once in the literature,39 although no structural
evidence has been presented. At the same time, all the
measured spectral properties of the described adduct
were identical with those of the respective porphyrin
dication. In view of the present discussion, it seems
probable that the reported H2TPP/DDQ complex was in
fact the salt of the porphyrin dication with the conjugate
base of hydroquinone.
The last step of the sequence is the demetalation of
metallotetrabenzoporphyrins (Scheme 4, l), which is
essential to gaining access to Ar4TBP(CO2Me)8 free bases
and subsequently to the other metal derivatives. The
necessity of demetalation imposed quite strict constraints
on the choice of the metal required for oxidation. On one
hand, this metal had to give stable complexes with Ar4-
TCHP(CO2Me)8’s, capable of sustaining the aromatiza-
tion; on the other, the resulting MAr4TBP(CO2Me)8’s had
to be labile enough to permit effective demetalation.
Choosing the metal was especially difficult because the
basicity of Ar4TCHP(CO2Me)8’s is generally a few orders
of magnitude higher than that of the corresponding Ar4-
TBP(CO2Me)8’s,5i making the metal complexes of the
latter much more robust. In general, metal affinity of
porphyrins decreases as their basicity increases. Basicity
is affected by porphyrin nonplanarity34 and extended
π-conjugation.5i Tetrabenzoporphyrins are weaker bases
than nonextended porphyrins10 owing to the influence of
the extended π-system, which acts as an absorber of
electron density, pulling it away from the core nitrogens
and making them more electron defficient.5h As a result,
tetrabenzoporphyrins form much more stable metal
derivatives, resembling in this respect phthalocyanines.
For example, complexes of planar TBP’s even with Zn
require treatment with sulfuric12 or hot phosphoric9a acid
to complete removal of the metal, while Pd and Ni, whose
complexes even with nonextended porphyrins are among
the most stable ones known,40 cannot be removed from
TBP’s without destroying the macrocycle.
Due to the effect of nonplanarity, Ar4TBP’s exhibit
higher basicities than planar TBP’s, and, consequently,
their metal complexes are more labile. For example,
unlike ZnTBP, ZnPh4TBP can be effectively demetalated
by TFA in chloroform,3j,15b which, in principle, makes Zn
a suitable candidate for the insertion/oxidation/demeta-
lation sequence. Unfortunately, Zn complexes with Ar4-
TCHP(CO2Me)8’s are so unstable that their aromatization
is extremely ineffective (see above). In contrast, Ni and
Pd complexes were excellent in aromatization, but re-
moval of metals from either Ni or Pd Ar4TBP(CO2Me)8’s
is still impossible without destroying the macrocycles. In
our experiments we went through a number of metals,
looking for the one that would permit the aromatization,
but at the same time would allow regeneration of Ar4-
TBP(CO2Me)8 free bases. The best metal found so far is
Cu.
Generally, SET from a metalloporphyrin either leaves
the unpaired spin to reside on the porphyrin macrocycle,
yielding a metalloporphyrin cation radical, or changes the
formal oxidation state of the metal, causing relatively
little perturbation of the porphyrin electronic system.37
Porphyrinates of electroactive metals, such as Fe, Co, and
Mn, react with oxidants primarily in this latter way,
which explains why we could not observe aromatization
of the corresponding metallo-tetracyclohexenoporphyrins.
Complexes of metals with stable oxidation states (Ni,
Pd, Cu) on the contrary give metalloporphyrin cation
radicals with spin density delocalized over the porphyrin
macrocycle. Similar to cation radicals of other aromatic
molecules containing “benzylic”-type R-hydrogen atoms,
these metalloporphyrin cation radicals are likely to lose
protons to a concomitant base,36 resulting in metallopor-
phyrin radicals. The abstraction of hydrogen atoms from
the latter seems like a quite probable scenario. Given that
the semiquinone anion radical can act as both the base
and the scavenger of hydrogens, the overall dehydroge-
nation should be fast and effective.
Unlike metal complexes, tetracyclohexenoporphyrin
free bases do not aromatize, but upon mixing with DDQ
quickly form dications. Several scenarios of this trans-
formation are plausible. On one hand, nonplanar tetra-
cyclohexenoporphyrins possess such high proton affinities
that even the smallest increase in the medium acidity
would cause their immediate protonation. On the other
hand, unlike cation radicals of metalloporphyrins, cation
radicals of the free bases (H2P+•) are highly transient
species and can convert into the corresponding cations
by abstracting hydrogen atoms from the solvent.38
A
support of this latter pathway comes from the quantum
chemistry calculations. Apparently, the spin density in
the porphyrin cation radical H2Ph4TCHP+• resides pri-
marily on the meso-carbon and imine nitrogen atoms,
approximately matching the geometry of the a2u(π)
HOMO in the free base H2Ph4TCHP (see the Supporting
Information for the distribution of the spin density). Since
the meso-positions are hindered by the phenyl substitu-
ents, hydrogen atoms from the solvent most certainly
would become attached to the imine nitrogens, resulting
in the cations.
Cu complexes of Ar4TCHP(CO2Me)8’s are very effective
in aromatization and indeed Cu can be removed from the
(36) See, for example: Utley, J . H. P.; Rozenberg, G. G. Tetrahedron
2002, 58, 5251 and references therein.
(37) Kadish, K. M. Electrochemistry of Metalloporphyrins in Non-
aqueous Media. In The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic Press: New York, 2000; Chapter
55.
(38) Inisan, C.; Saillard, J . Y.; Guilard, R.; Tabard, A.; Le Mest, Y.
New J . Chem. 1998, 22, 823.
(39) Mohajer, D.; Dehghani, H. J . Chem. Soc., Perkin Trans. 2 2000,
199.
(40) Buchler, J . W. Static coordination chemistry of metalloporphy-
rins. In Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevi-
er: New York, 1975; Chapter 5.
528 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis of Tetrabenzoporphyrins
SCHEME 5a
resulting tetrabenzoporphyrins; however, demetalation
of CuAr4TBP(CO2Me)8’s still required strong acidic condi-
tions, e.g. prolonged treatment with concentrated H2SO4
(Scheme 4, l). Notably, CuAr4TCHP(CO2Me)8’s could be
fully demetalated upon treatment with glacial AcOH.
According to the scale of Falk, Phillips, and Buchler, such
reactivity places CuAr4TCHP(CO2Me)8’s into one of the
low-stability classes (Class IV), while CuAr4TBP(CO2-
Me)8’s belong to the much more stable Class II (see ref
40 for details). Despite the harsh conditions required for
demetalation, the yields of the free base tetrabenzopor-
phyrins 8a -c were close to quantitative. Obviously,
hydrolysis of the side methyl ester groups accompanied
the removal of metal, but re-esterification could be easily
achieved by simply pouring the reaction mixtures into
MeOH and stirring the solutions overnight. Demetalation
of metalloporphyrins Cu -8d and Cu -8e, however, was
more problematic. In Cu -8d (Y ) 4-MeO), the presence
of electron-rich meso-aryl rings evidently facilitated
undesired side reactions, e.g. sulfonation, and the target
free base could be isolated in a quite poor yield (<5%).
In contrast, electron-withdrawing nitro groups in Cu -8e
(Y ) NO2) made this complex extremely robust. Even
after keeping Cu -8e in warm H2SO4 for several days Cu
was still partially retained in the porphyrin. Neverthe-
less, up until now we were unable to find a metal better
suited for the aromatization/demetalation sequence than
Cu.
Ar4TBP(CO2Me)8 free bases 8a -e as well as the metal
complexes were isolated as dark blue-green crystalline
solids, soluble in THF, CH2Cl2, and CHCl3 and virtually
insoluble in alcohols and ether. The overall yields of
tetrabenzoporphyrins 8a -e for the five-step sequence,
beginning with tetrahydroisoindole ester 5a , vary in the
range 20-55%. The yields depend on the nature of the
Y group, reaching their maximum at 45-55% for the
meso-tetraphenyl derivative (8a , Y ) H).
Ben zo-Un su b st it u t ed m eso-Tet r a a r ylt et r a b en -
zop or p h yr in s (Ar 4TBP ). Although benzo-unsubstituted
tetraaryltetracyclohexenoporphyrins (Ar4TCHP) have been
known for more than a decade, no attempts to aromatize
these porphyrins into the corresponding Ar4TBP’s by
oxidation have been reported. This fact from the begin-
ning kept us doubtful if such a conversion was at all
possible. Nevertheless, synthesis of benzo-unsubstituted
Ar4TBP’s via aromatization of Ar4TCHP’s appeared to be
quite convenient and versatile. The route to Ar4TBP’s is
shown in Scheme 5.
In the beginning, cyclohexene was transformed into
1-phenylsulfonylcyclohexene 4b in 80% overall yield by
using a reliable procedure, suitable for bulk preparations
(Scheme 5, a).27 As mentioned above, commercially avail-
able 1-nitrocyclohexene 4c could be used instead of 4b
in the following Barton-Zard reaction with ethyl iso-
cyanoacetate (Scheme 5, b). However, 4c is a costly
reagent, and the condensation involving sulfone 4b
proceeded, in our hands, much more smoothly, giving the
desired tetrahydroisoindole ester 5c in higher purity and
almost quantitative yield. Tetrahydroisoindole 6b was
obtained from 5c by refluxing the latter with an excess
of KOH in ethylene glycol (Scheme 5, c). In a routine
procedure, compound 6b was introduced directly into the
subsequent Lindsey synthesis (Scheme 5, d) without
intermediate isolation and purification. The yields of the
a
Reagents and conditions: (a) (i) PhSCl, CH2Cl2, rt; (ii) MCPBA,
CH2Cl2, rt, or oxone, MeOH-water; (iii) Et3N (80% for three steps);
(b) CNCH2CO2Et, tBuOK, THF, 0 °C (90%, starting with 4b); (c)
KOH, ethylene glycol, reflux, 1 h (pyrrole introduced directly to
the next reaction); (d) ArCHO, BF3‚Et2O, CH2Cl2, rt, 2 h, then
DDQ, overnight (yields for steps c + d are shown in the table); (e)
metal salt, solvent (85-98%, see text for details); (f) DDQ, THF,
reflux, 15-20 min (25-95%); (g) polyphosphoric acid, 85-90 °C,
4-5 h (70-80%).
resulting Ar4TCHP’s 9a ,b were quite high, i.e., up to 50%.
These porphyrins were crystallized from CH2Cl2-ether
mixtures and isolated as salts of the corresponding
dications (usually chlorides). The dark-green crystalline
dications are poorly soluble in THF and CH3CN, but their
solubility increases in the presence of acids, such as
AcOH or TFA.
Metal complexes of porphyrins 9a ,b were prepared
(Scheme 5, e) under the same conditions as were the Ar4-
TCHP(CO2Me)8’s. The insertion of Pd in CH3CN was
hampered by very low solubilities of both the parent
porphyrins and the metalated products, resulting in
incomplete conversions. Nevertheless, large differences
between the affinities of PdAr4TCHP’s and the corre-
sponding porphyrin dications to silica made it easy to
separate the metal-free porphyrins and recycle them.
Insertion of Pd in PhCN, on the other hand, was smooth
and occurred quantitatively after 2-3 min of refluxing
the mixtures.
Metalloporphyrins M-9a ,b (M ) Ni, Cu, Pd) were
readily aromatized by DDQ into MAr4TBP’s (M-10a ,b).
The yields of Ni and Cu complexes, however, were
somewhat lower compared to the analogous MAr4TBP-
(CO2Me)8’s, since the aromatization, especially in the case
of Ni complexes, was complicated by the formation of
J . Org. Chem, Vol. 69, No. 2, 2004 529

Finikova et al.
F IGURE 1. Absorption and corrected emission spectra (insets) of Ar4TCHP(CO2Me)8’s (a) and Ar4TBP(CO2Me)8’s (b): black lines,
free bases; red lines, Pd complexes. The letters “f” and “p” indicate fluorescence and phosphorescence, respectively. Ar ) 4-MeO2C-
C6H4.
TABLE 1. P h otop h ysica l Da ta for Ar 4TCHP ’s (9),
undefined poorly soluble bright-green byproducts. These
impurities, however, could be easily removed owing to
Ar 4TCHP (CO2Me)8’s (7), Ar 4TBP ’s (10), a n d
Ar 4TBP (CO2Me)8’s (9) a n d Th eir P d Com p lexes in DMF
their very high affinity to silica. The preferred solvent
for aromatizations is THF, in which the yields of MAr4-
TBP’s varied from 25-30% for Ni-10a to 55% for Ni-10b
to 60-80% for Cu -10a ,b. The aromatization of P d -9a ,b
was nearly quantitative (95%). It should be mentioned
(Ar ) 4-C6H4-CO2Me)
absorption, λmax (nm)
emissiona
λmax (nm)
porph
9b
Soret
Q
φb
443
442
428
431
469
485
444
538, 610, 677
537, 607, 676
539, 574
760 (f)
752 (f)
0.015
0.014
7b
that
a similar trend has been recently observed
P d -9b
P d -7b
10b
8b
P d -10b
in aromatizations leading to tetraaryltetra[2,3]naph-
thaloporphyrins,25b where Pd complexes clearly showed
an improved performance over some other metal com-
plexes. The reasons why Pd derivatives behave better in
aromatizations are currently not understood and require
further studies.
540, 575
593, 642, 706
600, 652, 712
588, 633
727, 811 (f)
737, 826 (f)
645, 705 (f)
815 (p)
648, 709 (f)
796 (p)
0.027
0.022
0.0006
0.106c
0.0005
0.026d
P d -8b
459
589, 639
Sulfuric acid could not be used for demetalation of Cu
complexes of benzo-unsubstituted Ar4TBP’s, since these
porphyrins are susceptible to electrophilic substitution.9a,41
However, quantitative removal of Cu could be achieved
after treating CuAr4TBP’s with hot (80-90 °C) polyphos-
phoric acid for 4-5 h. It was crucial, however, to
completely dissolve the Cu complexes, which required
taking them as fine powders and rigorously stirring the
reaction mixtures.
Sp ectr oscop ic P r op er ties of P or p h yr in s a n d X-
r a y Str u ctu r e of NiP h 4TBP (CO2Me)8 (Ni-8a ). In the
past, Ar4TBP’s have not been easily accessible, and
therefore only very few studies of their spectroscopic
properties have been accomplished. No doubt these
molecules present an interesting class of chromophores,
and their comprehensive photophysical assessment is yet
to be done. Here, we would like to briefly illustrate the
key spectroscopic features of the new Ar4TBP’s, empha-
sizing the difference between them and the Ar4TCHP’s,
which bear exactly the same peripheral substituents but
lack the extended π-system. A table containing the
relative oscillator strengths for all the porphyrins syn-
thesized in this work and their metal complexes is given
in the Supporting Information. Here we discuss only the
free base Ar4TCHP’s and Ar4TBP’s and the corresponding
Pd complexes. Usually, free base porphyrins exhibit
a
f ) fluorescence, including delayed fluorescence; p ) phos-
b
phorescence. Quantum yields were measured with ZnTPP as a
standard (φ ) 0.033 in deoxygenated benzene).46 Solutions were
deoxygenated by prolonged bubbling of Ar. c τ ) 105 µs. τ )
d
32 µs.
relatively strong S1 f S0 fluorescence, while in Pd-
porphyrins, Pd significantly raises the probability of the
intersystem crossing into the triplet state T1, making T1
f S0 phosphorescence their predominant emission.42
The absorption and emission spectra of the free base
octamethoxycarbonylporphyrins and their Pd complexes
are shown in Figure 1 as examples, and their basic
photophysical data are compiled in Table 1.
Similar to other nonplanar porphyrins, the absorption
bands of Ar4TCHP’s (9) and Ar4TCHP(CO2Me)8’s (7) are
broadened and red-shifted compared to those of tetra-
phenylporphyrin (TPP). The effect of the macrocycle
distortion on the spectra of porphyrins has been much
discussed in the literature.43 Compared to the free bases,
PdAr4TCHP and PdAr4TCHP(CO2Me)8 exhibit blue-
shifted Soret bands, and have two peaks of almost equal
intensity in the Q-band region. Free bases 9b and 7b
fluoresce weakly (φ ≈ 0.015), compared to H2TPP (φ )
0.11),44 and reveal extremely large Stokes shifts (1613
(42) Eastwood, D.; Gouterman, M. J . Mol. Spectrosc. 1970, 35, 359.
(43) Haddad, R. E.; Gazeau, S.; Pecaut, J .; Marchon, J . C.; Medforth,
C. J .; Shelnutt, J . A. J . Am. Chem. Soc. 2003, 125, 1253 and references
therein.
(41) (a) Berezin, B. D.; Potapova, T. I.; Platonova, M. V. Izv. Vyssh.
Uchebn. Zaved. Khim. Khim. Tekhnol. 1981, 24, 160. (b) Potapova, T.
I.; Petrova, R. A.; Berezin, B. D.; Kharitonov, S. V.; Kolesova, N. N.
Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 1984, 27, 1017.
(44) Seybold, P. G.; Gouterman, M. J . Mol. Spectrosc. 1969, 31, 1.
530 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis of Tetrabenzoporphyrins
cm-1 for 9b). Interestingly, Pd complexes of both Ar4-
TCHP and Ar4TCHP(CO2Me)8 are practically not at all
emissive, which is likely the result of strong internal
conversions from the T1 states. Large Stokes shifts, low
emission quantum yields, and short lifetimes are well-
known photophysical attributes of nonplanar porphy-
rins.45
The absorption bands of Ar4TBP’s are shifted to the
red compared to those of Ar4TCHP’s. Since all the
substituents are identical and the degrees of nonplanarity
in Ar4TBP’s and Ar4TCHP’s are nearly the same,5i the
extra red shifts in Ar4TBP’s are caused solely by the extra
π-extension. Noteworthy is a much larger influence of the
methoxycarbonyl groups in the case of Ar4TBP’s (8b vs
10b), compared to the analogous Ar4TCHP’s (7b vs 9b).
Obviously, electronic coupling of substituents to the cores
is mediated by extended π-conjugation.
F IGURE 2. X-ray crystallographic structure of NiPh4TBP-
(CO2Me)8 (Ni-8a ), shown together with its distortion modes,
as deconvoluted by NSD.47
The extended π-conjugation has significant effect on
Ni-8a , i.e., 3.32 Å, suggesting that coordination to the
Ni(II) ion affects Ar4TCHP’s and Ar4TBP’s in a similar
manner.
the emission properties of Ar4TBP’s. The Stokes shifts
of the Ar4TBP fluorescence fall down to 400-500 cm-1
,
while the fluorescence quantum yields of the free bases
8b and 10b increase about 2-fold compared to the
analogous Ar4TCHP’s. A much stronger increase is seen
for the phosphorescence of the Pd complexes P d -8b and
especially P d -10b, whose emission quantum yield is in
the same order magnitude as that of Pd tetraarylpor-
phyrins.9a,42 It is likely that extra π-extension decreases
the probability of nonemissive energy loss by making the
Ar4TBP macrocycles more rigid. Notably, the addition of
methoxycarbonyl groups in P d -10b slightly raises the
energy of the triplet state but also decreases the emission
lifetime almost 3-fold.
Finally, we would like to mention that the NMR
spectra of complex Ni-8a in DMSO-d6 exhibit severe line
broadening, typical for paramagnetic species. The spectra
of Ni complexes of Ar4TCHP’s and benzo-unsubstituted
Ar4TBP’s, on the other hand, are normally resolved. A
possible interpretation of the unusual behavior of 8a
would be the formation of a high-spin complex upon
binding of the DMSO molecule to NiAr4TBP(CO2Me)8.
Several examples of high-spin Ni-porphyrin complexes
with oxygen-containing donors have been reported in the
literature.49 Usually, the trend to bind extra ligands by
Ni-porphyrins is attributed to the decreased basicities of
the corresponding porphyrin free bases. The basicities
of Ar4TBP(CO2R)8’s have been shown to be very low.5i
It is well-known that nonplanarity plays a major role
in optical and other physical properties of porphyrins.1b
For extended porphyrins, however, the influence of
nonplanarity is not yet well documented, as all the
available structural information is limited to only two
structures, i.e., ZnPh4TBP5e and the free base Ph4TBP-
(CO2Me)8.5i Here we present a new X-ray structure of a
metallotetrabenzoporphyrin, i.e., NiPh4TBP(CO2Me)8 (Ni-
8a ) (shown in Figure 2)
Con clu sion s
A general synthesis of polysubstituted tetraaryltetra-
benzoporphyrins (Ar4TBP) with and without functional
groups in the fused benzo rings has been developed. The
method relies on the oxidative aromatization of metal
derivatives of nonaromatized porphyrin precursors and
affords metallo-Ar4TBP’s in good yields. Subsequent
demetalation of CuAr4TBP’s by sulfuric or hot polyphos-
phoric acid opens a way to Ar4TBP free bases and to other
metal derivatives. The synthesis relies on inexpensive,
readily available starting materials and includes 6-7
stages, depending on the method used in the preparation
of the precursor porphyrins. A possible mechanism of the
oxidative aromatization of cyclohexenoporphyrins is dis-
cussed. Basic photophysical properties of a few newly
synthesized Ar4TCHP’s and Ar4TBP’s are reported along
with the first X-ray crystallographic structure of NiAr4-
TBP(CO2Me)8.
In brief, the complex shown above exhibits the largest
degree of distortion so far reported for extended porphy-
rins (Doop ) 3.43 Å). This distortion is heavily dominated
by saddling (B2u, 3.30 Å), but also includes considerable
ruffling (B1u, 0.93 Å) and in-plane distortions, A2g and
A1g. For comparison, total out-of-plane distortion (Doop
)
in the free base porphyrin 8a is 2.97 Å5i and in ZnPh4-
TBP5e it is 2.35 Å. The Doop of the earlier reported NiPh4-
TCHP,48 on the other hand, is quite close to the one in
(45) (a) Ravikanth, M.; Reddy, D.; Chandrashekar, T. K. Chem. Phys.
Lett. 1994, 222, 563. (b) Charlesworth, P.; Truscott, T. G.; Kessel, D.;
Medforth, C. J .; Smith, K. M. J . Chem. Soc., Faraday Trans. 1994,
90, 1073. (c) Gentemann, S.; Medforth, C. J .; Forsyth, T. P.; Nurco, D.
J .; Smith, K. M.; Fajer, J .; Holten, D. J . Am. Chem. Soc. 1994, 116,
7363. (d) Gentemann, S.; Medforth, C. J .; Ema, T.; Nelson, N. Y.; Smith,
K. M.; Fajer, J .; Holten, D. Chem. Phys. Lett. 1995, 245, 441-447. (e)
Gentemann, S.; Nelson, N. Y.; J aquinod, L.; Nurco, D. J .; Leung, S.
H.; Medforth, C. J .; Smith, K. M.; Fajer, J .; Holten, D. J . Phys. Chem.
B 1997, 101, 1247-1254. (f) Sazanovich, I. V.; Galievsky, V. A.; van
Hoek, A.; Schaafsma, T. J .; Malinovskii, V. L.; Holten, D.; Chirvony,
V. S. J . Phys. Chem. B 2001, 105, 7818.
Exp er im en ta l Section
tert-Butyl isocyanoacetate, ethyl isocyanoacetate, and benzyl
isocyanoacetate were prepared according to the published
procedures.50 Compounds 3 and 3a were synthesized from
(48) Barkigia, K. M.; Renner, M. W.; Furenlid, L. R.; Medforth, C.
J .; Smith, K. M.; Fajer, J . J . Am. Chem. Soc. 1993, 115, 3627.
(49) Hambright, P. Chemistry of water soluble porphyrins. In The
Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.;
Academic Press: New York, 2000; Chapter 18.
(46) Quimby, D. J .; Longo, F. R. J . Am. Chem. Soc. 1975, 97, 5111.
(47) (a) J entzen, W.; Song, X.-Z.; Shelnutt, J . A. J . Phys. Chem. B
1997, 101, 1684-1699. (b) J entzen, W.; Ma, J . G.; Shelnutt, J . A.
Biophys. J . 1998, 74, 753-763.
J . Org. Chem, Vol. 69, No. 2, 2004 531

Finikova et al.
sulfolene 1a in 86% yield, and compound 4b was synthesized
from cyclohexene in 80% yield according to the published
method.27 The cis isomer of 4a (cis-4a ) was synthesized in 85%
yield from cis-2,27 which was obtained from commercially
available cis-1,2,3,6-tetrahydrophthalic anhydride in 95%
yield. Compound trans-4a was synthesized from trans-2 in 88%
yield following the same method.27 trans-2 was obtained in 85%
yield from sulfolene 1a and dimethyl maleate.31 Alternatively,
trans-4a was synthesized by the Diels-Alder reaction from
the mixture of sulfones 3 and 3a and DMM in 54% yield.31
The reported melting points are uncorrected.
was added. The organic phase was washed with water and
brine and dried over Na2SO4 and the solvent was evaporated
in a vacuum. The residue was purified on a short silica gel
column (eluent CH2Cl2-THF, 20:1) to give 6a (0.54-0.58 g)
as a colorless crystalline residue. Pyrrole 6a prepared by this
method could be stored at 4 °C without noticeable decomposi-
tion for at least 10 days. 1H NMR (CDCl3) δ 8.05 (br s, 1H),
6.5 (d, 2H), 3.65 (s, 6H), 2.88-3.27 (m, 6H); ES HRMS calcd
for C12H15NO4 + Na 260.2416, found 260.2411.
P or p h yr in s 7a -e via th e Lin d sey Meth od . Pyrrole 6a
(2.5 mmol, 0.59 g) was dissolved in 250 mL of CH2Cl2, and an
aromatic aldehyde (2.7 mmol) was added. The mixture was
stirred under Ar for 10 min in the dark at rt. BF3‚Et2O (0.5
mmol, 0.071 g) was added in one portion, and the mixture was
stirred at rt for an additional 2 h. DDQ (2.8 mmol, 0.63 g) was
added, and the mixture was left overnight under continuous
stirring. The resulting solution was washed with 10% aq Na2-
SO3 and with 5% aq HCl and dried over Na2SO4. The solvent
was evaporated in a vacuum and the residue was purified on
a silica gel column (eluent CH2Cl2-THF, then CH2Cl2-THF-
AcOH, green band collected), and then by repetitive precipita-
tion from CH2Cl2-AcOH (10:1) with hexane. For further
purification, porphyrins were converted into Cu complexes,
chromatographed on silica gel (eluent CH2Cl2-THF), and
demetalated by TFA. The free bases were obtained by washing
the solutions of the porphyrin dications in CH2Cl2 with 10%
aq Na2CO3, followed by reducing the solvent volumes to a few
milliliters and precipitating the red-brown solids with hex-
ane.51 7a : yield 365-445 mg, 45-55%; mp >300 °C; UV-vis
(CH2Cl2-Et3N, 9:1) λmax (log ꢀ) 437 (5.24), 537 (4.08), 611 (3.54),
677 nm (3.24); 1H NMR (CDCl3-TFA) δ 8.41-7.92 (m, 20 H),
2.2-3.6 (m, 48H); MALDI, m/z for C76H70N4O16 + H calcd
1296.39, found 1295.44. 7b: yield 335-430 mg, 35-50%; mp
>300 °C; UV-vis (CH2Cl2-Et3N, 9:1) λmax (log ꢀ) 445 (5.15),
539 (4.10), 611 (3.75), 675 nm (3.57); 1H NMR (CDCl3) δ 8.52-
8.19 (m, 16H), 4.1 (s, 12H), 2.4-4.0 (m, 48H), -2.4 (br s, 2H);
MALDI, m/z for C84H78N4O24 + H calcd 1528.53, found 1528.43.
7c: yield 300-400 mg, 30-40%; mp >300 °C; UV-vis (CH2-
Cl2-Et3N, 9:1) λmax (log ꢀ) 442 (5.22), 538 (4.17), 613 (3.69),
681 nm (3.22); 1H NMR (CDCl3-TFA) δ 8.1-8.3 (m, 16H),
2-Alk oxyca r bon yl-4,5,6,7-tetr a h yd r oisoin d oles (5a-c).
The pyrrole esters 5a -c were synthesized by using a method
similar to that published previously.26b THF was distilled over
LiAlH4 immediately prior to the synthesis. A solution of
isocyanoacetate (7 mmol) in 20 mL of THF was added to a
stirred suspension of tBuOK (0.9 g, 7 mmol) in 20 mL of THF
and kept on an ice bath under Ar. A solution of sulfone (6
mmol) in 10-20 mL of THF was added dropwise to the
mixture, after which the ice bath was removed, and the
mixture was left to react at rt under continuous stirring. After
4 h the volume of the mixture was reduced by rotary evapora-
tion and CH2Cl2 was added. The resulting solution was washed
with water and brine and dried over Na2SO4. The solvents
were removed in a vacuum, and the product was purified on
a short (2 × 10 cm2) silica gel column (CH2Cl2-THF, 20:1).
The products were recrystallized from ether-hexane (5a ,b)
or hexane (5c). cis-5a : yield 1.62 g, 80%, white crystals, mp
1
126-127 °C; H NMR (CDCl3) δ 9.0 (br s, 1H), 6.61 (d, 1H),
3.66 (s, 3H), 3.68 (s, 3H), 2.6-3.5 (m, 6H), 1.50 (s, 9H); ES
HRMS calcd for C17H23NO6 + Na 360.3574, found 360.3577.
trans-5a : 1.92 g, 95%, white crystals, mp 173-175 °C; 1H
NMR (CDCl3) δ 8.95 (br s, 1H), 6.65 (d, 1H), 3.69 (s, 3H), 3.70
(s, 3H), 2.8-3.4 (m, 6H), 1.55 (s, 9H); ES HRMS calcd for
C
17H23NO6 + Na 360.3574, found 360.3571. cis-5b: yield 1.67
g, 75%, white powder, mp 142-143 °C; 1H NMR (CDCl3) δ 8.95
(br s, 1H), 7.25-7.45 (m, 5H), 6.65 (d, 1H), 5.29 (q, 2H), 3.66
(s, 3H), 3.67 (s, 3H), 2.8-3.5 (m, 6H); 13C NMR (CDCl3) δ 161.3,
161.2, 161.1, 124.0, 116.1, 115.6, 115.6, 113.1, 107.0, 106.8,
105.1, 53.3, 39.5, 28.5, 28.4, 11.4, 9.9; ES HRMS calcd for
C
20H21NO6 + Na 394.3736, found 394.3740. 5c: yield 1.04 g,
2.25-4.0 (m, 48H), -0.5 (br s, 4H); MALDI, m/z for C76H66
-
1
90%, pale yellow crystals, mp 82-83 °C; H NMR (CDCl3) δ
8.76 (br s, 1H), 6.64 (s, 1H), 4.29 (q, 2H), 2.81 (t, 2H), 2.54 (t,
2H), 1.74 (m, 4H), 1.34 (t, 3H); 13C NMR (CDCl3) δ 149.6, 115.7,
109.4, 106.8, 105.2, 47.3, 11.0, 10.8, 9.5, 2.1; ES HRMS calcd
for C11H15NO2 + Na 216.2321, found 216.2318.
Br4N4O16 + H, calcd 1611.97, found 1612.10. 7d : yield 310-
400 mg, 35-45%; mp >300 °C; UV-vis (CH2Cl2-Et3N, 9:1)
λmax (log ꢀ) 441 (5.25), 538 (4.08), 582 (3.79), 611 (3.69), 683
1
nm (3.45); H NMR (CDCl3) δ 8.15-7.95 (m, 8H), 7.35-7.20
(m, 8H, overlapped w/solv), 4.1 (s, 12H), 2.5-3.7 (m, 48H),
-2.44 (br s, 4H); MALDI, m/z for C80H78N4O20 + H, calcd
1416.49, found 1416.07. 7e: yield 185-230 mg, 20-25%; mp
>300 °C; UV-vis (CH2Cl2-Et3N, 9:1) λmax (log ꢀ) 456 (4.99),
4,5,6,7-Tetr a h yd r oisoin d ole 6a , Meth od A. tert-Butyl
ester 5a (0.5 g, 1.48 mmol) was dissolved in TFA (5 mL), and
the solution was left for 30 min under Ar in the dark at rt.
CH2Cl2 (20 mL) was added, and the mixture was poured into
cold water. The organic layer was collected, washed with
water, then with 10% solution of Na2CO3, and with water
again, and dried over Na2SO4. The solvent was removed in a
vacuum, and the residue was purified on a silica gel column
(eluent CH2Cl2-THF , 20:1). The solvents were evaporated to
give 6a as a white crystalline solid (105 mg, 30%). Pyrrole 6a
gradually decomposes upon storing at rt. Therefore, it is
desirable to use it up quickly following the preparation.
4,5,6,7-Tetr a h yd r oisoin d ole 6a , Meth od B. Benzyl ester
5b (1.0 g, 2.70 mmol) was dissolved in THF (30 mL), Et3N (0.35
mL) was added, and the vial was flushed with hydrogen.
Pearlman’s catalyst32 Pd(OH)2/C (0.1 g) was cautiously added,
and the reaction mixture was thoroughly stirred under hy-
drogen until the uptake of the gas stopped, and the TLC (CH2-
Cl2-THF, 20:1) showed that no 5b was present in the mixture.
The catalyst was filtered off, the solvent was removed under
reduced pressure, and the residue was refluxed in ethylene
glycol for 40 min. The mixture was cooled to 0 °C and CH2Cl2
1
544 (4.07), 615 (3.78), 689 nm (3.28); H NMR (CDCl3) δ 8.67
(m, 8H), 8.33-8.45 (m, 8H), 2.5-3.6 (m, 48H), -2.3 (br, 2H);
MALDI, m/z for
1475.78.
C76H66N8O24 + H, calcd 1476.38, found
P or p h yr in 7a via th e Ad ler -Lon go Meth od . tert-Butyl
ester 5a (200 mg, 0.59 mmol), PhCHO (63 mg, 0.59 mmol),
and TosOH (0.015 mg, 0.06 mmol) were dissolved in 12 mL of
AcOH, and the mixture was refluxed in the dark under Ar.
After 30 min the air was let into the flask, and the mixture
was refluxed for 8 h. During this time the color gradually
changed from dark-purple to dull green. The mixture was
allowed to cool, stirred overnight, diluted with CH2Cl2, washed
with water, with 10% aq Na2CO3, and with 5% aq HCl, and
dried over Na2SO4. The solvent was evaporated to dryness,
and the resulting dark material was purified on a silica gel
column (eluent CH2Cl2-THF, then CH2Cl2-THF-AcOH). The
bright green fraction was collected. The chromatography was
repeated twice and followed by multiple precipitations of the
(51) 13C NMR spectra of porphyrins 7a -e are not given. These
compounds were isolated as mixtures of multiple stereoisomers and,
therefore, their 13C NMR spectra are not informative for identification
purposes.
(50) (a) Ugi, L. Chem. Ber. 1961, 94, 2814. (b) Tietze, L. F.; Eicher,
T. Reaktionen und Synthesen im organisch-chemischen Praktikum und
Forschungslaboratorium; Georg Thieme Verlag: New York, 1991.
532 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis of Tetrabenzoporphyrins
product from CH2Cl2-THF-AcOH by hexane. 7a was isolated
identified by their UV-vis spectra only. See Supporting
Information for details. Ni-9a : mp >300 °C; UV-vis (CH2-
Cl2) λmax (log ꢀ) 424 (5.32), 544 (4.27), 5.81 (4.27); 1H NMR
(CDCl3) δ 7.80 (m, 12H), 7.5 (m, 8H), 2.15 (s, 16H), 1.35 (s,
16H); 13C NMR (CDCl3) δ 144.3, 142.4, 141.2, 134.4, 128.7,
128.2, 117.2, 26.6, 24.2; MALDI, m/z for C60H52N4Ni, calcd
888.78, found 887.32. Cu -9a : mp >300 °C; UV-vis (CH2Cl2)
λmax (log ꢀ) 424 (5.30), 557 (4.30), 592 nm (4.08); MALDI, m/z
for C60H52N4Cu + H calcd 893.63, found 892.91. Ni-9b: mp
>300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 428 (5.35), 547 (4.35),
as the dication (28 mg, 11%).
P or p h yr in s 9a ,b. A mixture of pyrrole ester 5c (2.1 g, 10.9
mmol) and potassium hydroxide (∼85%, 19.7 mmol, 1.3 g) in
ethylene glycol (30 mL) was refluxed under Ar for 60 min. The
mixture was cooled to 0 °C and CH2Cl2 (100 mL) was added.
The organic phase was washed with water and with brine. The
product (pyrrole 6b) was extracted with CH2Cl2. The solution
was washed with water and brine and dried over Na2SO4, and
the solvent was evaporated in a vacuum. The residue was
purified on a short silica gel column (eluent CH2Cl2), and the
resulting solution was diluted with CH2Cl2 to about 1000 mL.
The vial was protected from light and flushed with Ar, and
the aromatic aldehyde (10 mmol) was added in one portion.
The solution was stirred for 10 min, after which BF3‚Et2O (2
mmol, 0.28 g) was added, and the mixture was stirred at rt
for 2 h. DDQ (11 mmol, 2.5 g) was added, and the mixture
was left overnight under continuous stirring. The resulting
green solution was washed with 10% aq Na2SO3, with 10% aq
Na2CO3, with 5% aq HCl, and finally with brine. The organic
layer was dried over Na2SO4 and reduced in volume to about
100 mL. Methyl tert-butyl ether or diethyl ether was carefully
laid over the surface of the CH2Cl2 solution to prevent rapid
mixing of the solvents, and the resulting mixture was left
overnight. Blue-green crystals formed, which were filtered off
and washed with methyl tert-butyl ether or ethanol. The
mother liqueur was evaporated to dryness and dissolved in
the minimally necessary volume of CH2Cl2, and the crystal-
lization procedure was repeated. The residue was filtered off
and washed with methyl tert-butyl ether or ethanol to give
the second crop as a fine green powder. 9a : yield 1.37 g, 54%;
mp >300 °C; UV-vis (CH2Cl2-TFA, 9:1) λmax (log ꢀ) 464 (5.37),
614 (4.07), 670 nm (4.32); 1H NMR (CDCl3) δ 8.36 (m, 8H), 7.8
(m, 12H), 2.46-2.50 (m, 8H), 1.98-2.01 (m, 8H), 1.62-1.64
(m, 8H), 1.1-1.20 (m, 8H), 0.23 (br s, 4H); 13C NMR (CDCl3)
δ 144.2, 139.1, 136.9, 135.3, 129.8, 128.9, 118.0, 24.8, 22.8;
MALDI, m/z for C60H54N4 + H calcd 832.10, found 831.45. 9b:
yield 1.4 g, 45%; mp >300 °C; UV-vis (CH2Cl2-TFA, 9:1) λmax
1
584 nm (4.35); H NMR (CDCl3) δ 7.97-8.25 (m, 16H), 4.00
(s, 12H), 2.12 (s, 16H), 1.35 (s, 16H); 13C NMR (CDCl3) δ 167.4,
145.2, 144.0, 141.9, 133.8, 129.9, 128.9, 115.9, 52.5, 26.3, 23.4;
MALDI, m/z for C68H60N4NiO8 + H calcd 1120.92, found
1119.36. Cu -9b: mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ)
429 (5.25), 562 (4.25), 597 nm (4.10); MALDI, m/z for C68H60N4-
CuO8, calcd 1125.77, found 1123.91.
P d -7a ,b a n d P d -9b. PdCl2 (88.7 mg, 0.5 mmol) was added
to a solution of a free base porphyrin (0.5 mmol) in CH3CN-
THF (1:1, 50-100 mL), and the mixture was refluxed for 30
min. An additional portion of PdCl2 (17.7 mg, 0.1 mmol) and
Et3N (1.01 g, 10 mmol) were added and the mixture was
refluxed for an additional 30 min. Alternatively, an excess of
PdCl2 (17 mg, 0.1 mmol) and a free base porphyrin (0.06 mmol)
were refluxed in PhCN (5-10 mL) for 3-5 min. The conversion
was monitored by UV-vis spectroscopy (solvent CHCl3-AcOH)
and considered complete after the Soret band of the dication
at 468-472 nm disappeared. The mixture was allowed to cool,
diluted with CH2Cl2, and filtered through a thin layer of Celite
to remove Pd black, and the solvent was evaporated. The
product was purified by chromatography on silica gel with CH2-
Cl2 for P d -9b, CH2Cl2-THF (20:1) for P d -7a , and CH2Cl2-
THF (12:1) for P d -7b as eluents. Pd-porphyrins appeared as
dark red bands. The solvent was evaporated and the residue
was either recrystallized from CH2Cl2-ether (P d -9b ) or
precipitated from CH2Cl2 with hexane (P d -7a ,b). P d -7a : yield
620-670 mg, 88-95%; mp >300 °C; UV-vis (CH2Cl2) λmax (log
ꢀ) 425 (5.22), 536 (4.22), 570 nm (4.04); 1H NMR (CDCl3) δ
8.0-8.15 (m, 8H), 7.7-7.8 (m, 12H), 2.45-3.65 (m, 48H);
MALDI, m/z for C76H68N4O16Pd + H calcd 1400.79, found
1400.58. P d -7b: yield 630 mg, 90%; mp >300 °C; UV-vis
1
(log ꢀ) 473 (5.40), 618 (4.18), 676 nm (4.40); H NMR (CDCl3)
δ 8.50-8.56 (m, 16H), 4.14 (s, 12H), 2.45-2.55 (m, 8H), 2.0-
2.1 (m, 8H), 1.6-1.7 (m, 8H), 1.15-1.25 (m, 8H), 0.69 (br s,
4H); 13C NMR (CDCl3) δ 167.5, 143.9, 142.5, 136.9, 135.8,
131.4, 103.2, 117.6, 53.1, 25.2, 22.8; MALDI, m/z for C68H62N4O8
+ H calcd 1064.24, found 1064.35.
1
(CH2Cl2) λmax (log ꢀ) 431 (4.91), 540 (3.92), 580 nm (3.76); H
NMR (CDCl3) δ 8.0-8.15 (m, 8H), 7.7-7.8 (m, 12H), 2.45-
3.65 (m, 48H); MALDI, m/z for C84H76N4O24Pd + H calcd
1631.93, found 1631.52. P d -9b: yield 500-515 mg, 85-88%;
mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 429 (5.30), 540 (4.29),
575 nm (4.18); 1H NMR (CDCl3) δ 8.15-8.4 (m, 8H), 4.1 (s,
12H), 2.3 (s, 16H), 1.4 (s, 16H); 13C NMR (CDCl3) δ 167.4,
145.9, 142.0, 140.5, 134.2, 129.8, 128.8, 118.5, 52.4, 26.4, 23.4;
MALDI, m/z for C68H60N4O8Pd + H, calcd 1168.65, found
1167.12.
Zn -7a -e. An excess of Zn(OAc)2‚2H2O was added to a
solution of a porphyrin (about 50 mg) in 50 mL of CHCl3/MeOH
(9:1). The mixture was stirred until the metal insertion was
complete (after about 15 min), as evidenced by UV-vis
spectroscopy. The mixture was washed with water and dried
over Na2SO4 and the solvent was evaporated in a vacuum. The
remaining solid was purified on a silica gel column with use
of a CH2Cl2-THF (20:1) mixture as an eluent. CH2Cl2 in this
procedure must be free from acid, as Zn complexes easily
undergo demetalation. Zn porphyrins were recovered in 95-
98% yields as dark red solids. As intermediate compounds, Zn -
7a -e were identified by their UV-vis spectra only. See
Supporting Information for details.
M-7a -e a n d M-9a ,b (M ) Cu , Ni). An excess of Ni(OAc)2‚
4H2O or Cu(OAc)2‚H2O was added to a solution of a porphyrin
(about 50 mg) in 50 mL of CHCl3/MeOH (9:1), and the mixture
was stirred at rt (Cu complexes) or refluxed for 10-15 min in
the presence of an excess of Et3N (Ni complexes). The conver-
sion was monitored by UV-vis spectroscopy (solvent CHCl3/
AcOH) and considered complete when the Soret band of the
dication at 468-472 nm disappeared. The mixture was washed
with 10% aq AcOH, with 10% aq NaHCO3, and with water
and dried over Na2SO4. The solvent was evaporated in a
vacuum, and the remaining material was purified on a silica
gel column. Metalloporphyrins were recovered as red solids
in 95-98% yields. Ni and Cu complexes of porphyrins 9a ,b
were additionally recrystallized from CH2Cl2-ether mixtures.
As intermediate compounds M-7a -e (M ) Cu , Ni) were
M-8a -e a n d M-10a ,b (M ) Ni, Cu , P d ). Metalloporphyrin
(M-7a -e or M-9a ,b) (1 equiv) was dissolved in 100-150 mL
of a dry solvent (THF for M-9a ,b, CH3CN for M-7a -e). A 2-fold
excess of DDQ (16 equiv) was added, and the mixture was
refluxed for 20-40 min. In the case of Cu -7e a longer refluxing
period (1-2 h) was required. During refluxing the color
changed from red-brown to deep green. The mixture was
allowed to cool, diluted with CH2Cl2, washed with a 10% aq
solution of Na2SO3, with water, and with brine, and dried over
Na2SO4. The solvent was removed in a vacuum, and the
remaining solid was purified on a silica gel column with CH2-
Cl2 for M-10a ,b and CH2Cl2/THF (20:1) for M-8a -e as eluents.
The first dark-green fraction was collected. The solvents were
evaporated and the residues were recrystallized from CH2Cl2-
ether to give the products in the form of blue-green crystals
(M-8a -e) or dark-green powders (M-10a ,b). Yields: M-8a -e
90-95%; Ni-10a 25-30%; Cu -10a 60-65%; Ni-10b 50-55%;
Cu -10b 75-80%; P d -10b 90-95%.
Ni-8a : mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 465 (5.34),
603 (4.34), 655 nm (4.92); 1H NMR (CDCl3) δ 7.8-8.1 (m, 20H),
7.42 (s, 8H), 3.85 (s, 24H); 13C NMR (CDCl3) δ 167.9, 139.4,
J . Org. Chem, Vol. 69, No. 2, 2004 533

Finikova et al.
139.0, 138.4, 132.8, 129.6, 129.5, 128.2, 125.1, 117.0, 52.5;
MALDI, m/z for C76H52N4NiO16 + H, calcd 1336.94, found
1335.04. Cu -8a : mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ)
mg, 0.23 mmol) were added to the solution, and the mixture
was stirred for 15 min at rt. The conversion of 7a dication into
the Zn complex was monitored by using UV-vis spectroscopy.
474 (5.51), 608 (4.38), 658 nm (5.02); MALDI, m/z for C76H52
-
The resulting mixture was washed with water, dried over Na2-
SO4, and filtered through a thin (about 1 cm) layer of silica
gel. The solvent was removed in a vacuum, and the remaining
solid was oxidized with DDQ (50 mg, 0.22 mmol). The following
workup was carried out as described above. The product Zn -
8a was separated from the remaining 7a dication by chroma-
tography on silica gel, using CH2Cl2-THF (20:1) and then
CH2Cl2-THF-AcOH to recover 7a . Zn -8a was recrystallized
from CH2Cl2-ether. Yield: 13-18 mg, 45-60%; mp >300 °C;
UV-vis (CH2Cl2) λmax (log ꢀ) 483 (5.55), 620 (4.37), 666 nm
(4.74); 1H NMR (DMSO-d6) δ 8.28-7.94 (m, 20 H), 7.45 (s, 8H),
3.81 (s, 24H); 13C NMR (DMSO-d6) δ 52.1, 118.2, 125.3, 127.8,
129.0, 129.2, 133.3, 139.3, 141.6, 142.8, 167.2; MALDI, m/z for
CuN4O16, calcd 1341.79, found 1339.99. P d -8a : mp >300 °C;
UV-vis (CH2Cl2) λmax (log ꢀ) 458 (5.39), 585 (4.12), 637 nm
1
(4.89); H NMR (CDCl3) δ 8.20 (d, 8H), 8.03 (t, 4H), 7.94 (t,
8H), 7.49 (s, 8H), 3.87 (s, 24H); 13C NMR (CDCl3) δ 167.9,
140.3, 138.7, 138.2, 133.4, 129.7, 128.8, 125.7, 119.7, 52.5;
MALDI, m/z for C76H52PdN4O16 + H, calcd 1384.66, found
1383.39. Ni-8b: mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 464
(5.38), 603 (5.18), 656 nm (4.96); 1H NMR (CDCl3) δ 8.06-
8.55 (m, 16H), 7.37 (s, 8H), 4.13 (s, 12H), 3.82 (s, 24H); 13C
NMR (CDCl3) δ 167.5, 166.6, 143.3, 139.2, 137.8, 133.1, 131.5,
130.7, 128.7, 124.9, 116.1, 52.6; MALDI, m/z for C84H60N4NiO24
+ H, calcd 1569.08, found 1568.97. Cu -8b: mp >300 °C; UV-
vis (CH2Cl2) λmax (log ꢀ) 471 (5.60), 613 (4.64), 662 nm (5.14);
MALDI, m/z for C84H60CuN4O24 + H, calcd 1573.93, found
1572.76. P d -8b (this compound was synthesized in 92% yield
by insertion of Pd into 8b free base in refluxing benzonitrile);
mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 458 (5.33), 589 (4.04),
C
76H52N4O16Zn + H, calcd 1343.63, found 1344.31.
Tetr a ben zop or p h yr in s 8a -c. Cu complex of a tetraben-
zoporphyrin (50-100 mg) was dissolved in 15-30 mL of
concentrated H2SO4 and left under stirring at rt for 24h. The
conversion was monitored by UV-vis spectroscopy, using HCl
concentrated as a solvent, and was considered complete when
the Soret band of the Cu complex completely disappeared. The
Soret band of the dication TBP appeared at 510-520 nm. The
solution was poured into 100 mL of MeOH (ice bath) and left
overnight under stirring in a closed vial. CH2Cl2 and then
water were added to the mixture. The organic layer was
separated and washed with 10% aq Na2CO3. If re-esterification
was complete, the aqueous layer remained colorless. The
organic solution was further washed with water and dried over
Na2SO4. The solvent was removed in a vacuum, and the
remaining solid was purified on a short silica gel column (2 ×
10 cm2), using a CHCl3/THF mixture (20:1) as an eluent. The
main bright-green fraction was collected and evaporated to
dryness, and the residue was recrystallized from CH2Cl2-
ether. Porphyrins 8a -c were isolated as blue-green crystals
in 90-95%. 8a : mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 479
(5.26), 598 (3.97), 653 (4.36), 709 nm (3.72); 1H NMR (CDCl3-
TFA) δ 11.00 (TFA + NH), 8.50-8.02 (m, 20H), 7.79 (s, 8H),
3.87 (s, 24H); 13C NMR (CDCl3-TFA) δ 167.8, 141.3, 137.9,
135.7, 132.4, 131.8, 131.7, 130.3, 125.9, 117.0, 53.5; MALDI,
m/z for C76H54N4O16 + H, calcd 1280.26, found 1279.32. 8b:
mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 480 (5.54), 598 (4.39),
647 (4.66), 708 nm (4.24); 1H NMR (CDCl3-TFA) δ 11.06 (TFA
+ NH), 8.68 (s, 16H), 7.77 (s, 8H), 4.24 (s, 12H), 3.83 (s, 24H);
13C NMR (CDCl3-TFA) δ 166.8, 166.7, 141.3, 136.0, 141.3,
132.9, 132.8, 131.5, 131.2, 125.7, 116.1, 53.2, 53.1; MALDI,
m/z for C84H62N4O24 + H, calcd 1512.40, found 1511.87. 8c:
mp >300 °C; UV-vis (CH2Cl2-TFA, 9:1) λmax (log ꢀ) 509 (5.67),
1
640 nm (4.89); H NMR (CDCl3) δ 8.62-8.29 (m, 16H), 7.76
(s, 8H), 4.16 (s, 12H), 3.82 (s, 24H); MALDI, m/z for C84H60N4O24-
Pd + H, calcd 1615.81, found 1615.53. Ni-8c: mp >300 °C;
UV-vis (CH2Cl2) λmax (log ꢀ) 464 (5.38), 605 (4.28), 657 nm
(4.95); 1H NMR (CDCl3) δ 7.81-8.03(m, 16H), 7.46 (s, 8H), 3.95
(s, 24H); 13C NMR (CDCl3) δ 168.0, 139.7, 138.2, 136.9, 134.8,
133.3, 129.1, 125.4, 124.7, 116.1, 53.4; MALDI, m/z for C76H48
-
Br4N4NiO16 + H, calcd 1652.52, found 1649.66. Cu -8c: mp
>300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 472 (5.25), 613 (4.16),
659 nm (4.82); MALDI, m/z for C76H48Br4CuN4O16 + H, calcd
1657.37, found 1656.88. Ni-8d : mp >300 °C; UV-vis (CH2-
Cl2) λmax (log ꢀ) 470 (5.42), 603 (4.21), 654 nm (4.97); 1H NMR
(CDCl3) δ 7.84 (d, 8H), 7.52 (s, 8H), 7.38 (d, 8H), 4.12 (s, 12H),
3.88 (s, 24H); 13C NMR (CDCl3) δ 167.6, 160.9, 139.1, 138.6,
133.7, 131.0, 127.8, 124.8, 116.3, 114.7, 55.5, 52.2; MALDI,
m/z for C80H60N4NiO20 + H, calcd 1457.04, found 1455.01. Cu -
8d : mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 479 (5.40), 610
(4.27), 658 nm (4.87); MALDI, m/z for C80H60N4CuO20 + H,
calcd 1461.89, found 1459.30. Cu -8e: mp >300 °C; UV-vis
(CH2Cl2) λmax (log ꢀ) 469 (5.27), 612 (4.31), 664 nm (4.84);
MALDI, m/z for C76H48CuN8O24 + H, calcd 1521.78, found
1519.04. Ni-10a : mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ)
1
446 (5.11), 591 (4.01), 643 nm (4.73); H NMR (CDCl3) δ 8.47
(d, 8H), 7.74-7.84 (m, 12H), 7.02-7.13 (m, 16H); 13C NMR
data are not available due to very low solubility of this
compound; MALDI, m/z for C60H36N4Ni + H, calcd 872.65,
found 871.21. Cu -10a : mp >300 °C; UV-vis (CH2Cl2) λmax (log
ꢀ) 446/458 (5.16), 599 (4.11), 647 nm (4.78); MALDI, m/z for
C60H36N4Cu + H, calcd 877.50, found 875.26. Ni-10b: mp >300
°C; UV-vis (CH2Cl2) λmax (log ꢀ) 448 (5.04), 596 (3.99), 649 nm
(4.66); 1H NMR (CDCl3) δ 8.08-8.40 (m, 16H), 6.91-7.07 (m,
16H), 4.05 (s, 12H); 13C NMR (CDCl3) δ 167.6, 145.7, 138.5,
137.0, 134.2, 131.1, 130.8, 125.7, 123.7, 115.3, 52.9; MALDI,
m/z for C68H44N4NiO8 + H, calcd 1104.79, found 1103.92. Cu -
10b: mp >300 °C; UV-vis (CH2Cl2) λmax (log ꢀ) 445 (5.23), 602
(4.19), 650 nm (4.86); MALDI, m/z for C68H44CuN4O8 + H, calcd
1109.65, found 1107.32. P d -10b: mp >300 °C; UV-vis (CH2-
Cl2) λmax (log ꢀ) 433 (5.44), 584 (4.28), 633 nm (5.00); 1H NMR
(CDCl3) δ 8.37-8.56 (m, 16H), 7.08-7.21 (m, 16H), 4.16 (s,
12H); 13C NMR (CDCl3) δ 167.2, 146.1, 138.1, 137.6, 134.1,
130.8, 130.4, 125.7, 123.8, 117.3, 53.6; MALDI, m/z for
1
653 (4.72), 701 nm (4.45); H NMR (CDCl3-TFA) δ 8.2-8.4
(m, 16H), 7.86 (s, 8H), 3.97 (s, 24H); 13C NMR (CDCl3-TFA)
δ 168.0, 141.3, 136.9, 136.5, 133.7, 132.6, 132.5, 131.6, 127.6,
125.9, 116.2, 54.0; MALDI, m/z for C76H50Br4N4O16 + H calcd
1595.84, found 1596.98.
Tetr a ben zop or p h yr in 8a fr om Zn -8a . TFA (1 mL) was
added to a stirred solution of Zn -8a (∼20 mg, 0.015 mmol) in
15 mL of CH2Cl2, which resulted in an immediate change of
color from green to red-brown. The mixture was allowed to
react for 15 min, after which 50 mL of CH2Cl2 was added. The
solution was transferred into a separatory funnel and washed
with water, with NaOH (10% solution), and with water again
and dried over Na2SO4. The chromatographic purification of
the resulting solution on silica gel (CH2Cl2/THF (12:1)) afforded
8a in 95-97% yield.
C
68H44N4O8Pd + H, calcd 1152.52, found 1152.87.
Zn -8a . Zn -7a (30 mg, 0.022 mmol) was dissolved in 20 mL
of dry CH3CN. A 2-fold excess of DDQ (80 mg, 0.35 mmol) was
added, and the mixture was refluxed for approximately 1 h.
The UV-vis spectrum of the mixture revealed the presence
of the Soret bands of both the product Zn -8a and the dication
7a . The solvent was removed in a vacuum and the residue was
dissolved in CH2Cl2. The solution was washed with 10% aq
Na2SO3, with 5% HCl, and with brine and dried over Na2SO4.
MeOH (10 vol %) and an excess of Zn acetate dihydrate (50
Tetr a ben zop or p h yr in 10b. A solution of Cu -10b (50 mg,
0.045 mmol) in a small volume of CH2Cl2 (∼5 mL) was poured
into ∼30 mL of hexane and the solvents were evaporated in a
vacuum. Warm polyphosphoric acid (5 mL) was added to the
resulting fine powder, and the mixture was kept under stirring
at 85-90 °C in a sealed vial for 4-5 h. The UV-vis spectrum
of the mixture (CH2Cl2-THF-TFA) revealed the Soret band
of the dication of 10b at 502 nm. The demetalation was
534 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis of Tetrabenzoporphyrins
considered complete after the Soret band of the Cu complex
disappeared. The mixture was poured into warm water, and
the product was extracted with CH2Cl2. The organic layer was
washed with 10% aq Na2CO3 and with water, dried over Na2-
SO4, and evaporated to dryness. The resulting solid was
purified on a silica gel column with a CH2Cl2/THF (20:1)
mixture as an eluent. The dark-green band was collected, the
solvent was evaporated, and the residue was recrystallized
from CH2Cl2-ether to give 10b as a dark-green powder.
Yield: 33-38 mg, 70-80%; mp >300 °C; UV-vis (CH2Cl2) λmax
(log ꢀ) 467 (5.48), 595 (4.32), 644 (4.65), 701 nm (4.26); 1H NMR
(CDCl3) δ 8.63 (m, 16H), 7.2 (br, 8H), 4.17 (s, 12H), -1.05(br,
2H); 13C NMR (CDCl3) δ 167.8, 146.6, 135.3, 131.2, 130.7,
126.8, 124.7, 115.5, 53.1; MALDI, m/z for C68H46N4O8 + H,
calcd 1048.12, found 1047.56.
Anteon Inc. (USA; contract 02-5403-21-2) is gratefully
acknowledged. A.V.C. and O.S.F. acknowledge support
from the RFBR (grant 01-03-33097-A). O.S.F. acknowl-
edges support from the INTAS (grant YSF 2001/1-161).
The authors thank Ms. Natalie Kim for reviewing the
manuscript.
Su p p or tin g In for m a tion Ava ila ble: Details of X-ray
structure determination, quantum chemistry calculations, and
NSD (Normal-Coordinate Structural Decomposition), as well
as a table with UV-vis spectroscopic data for all newly
synthesized porphyrins and metalloporphyrins and copies of
their NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. Support from the National Iin-
stitutes of Health (USA; grant NS-31465) and from
J O0350054
J . Org. Chem, Vol. 69, No. 2, 2004 535