Meso Aryl Heptaphyrins: The First 30π Aromatic Expanded Porphyrins with an Inverted Structure

Article abstract of DOI:10.1021/ol000251c

Formula Represented Synthesis of new meso aryl 30π heptaphyrins 2, 3, and 4 is achieved. Spectroscopic studies reveal that 2, 3, and 4 are aromatic and possess an inverted structure.

Full text of DOI:10.1021/ol000251c

ORGANIC
LETTERS
2000
Vol. 2, No. 24
3829-3832
Meso Aryl Heptaphyrins: The First 30π
Aromatic Expanded Porphyrins with an
Inverted Structure
Venkataramana Rao. G. Anand,† Simi K. Pushpan,† Alagar Srinivasan,†
Seenichamy Jeyaprakash Narayanan,† Bashyam Sridevi,†
Tavarekere K. Chandrashekar,*,†,‡ Raja Roy,§ and Bhavani S. Joshi§
Department of Chemistry, Indian Institute of Technology, Kanpur - 208 016, India, and
Medicinal Chemistry DiVision, Central Drug Research Institute, Lucknow, India
tkc@iitk.ernet.in
Received August 31, 2000
ABSTRACT
Synthesis of new meso aryl 30π heptaphyrins 2, 3, and 4 is achieved. Spectroscopic studies reveal that 2, 3, and 4 are aromatic and possess
an inverted structure.
The unique physical and chemical properties and diverse
biomedical applications displayed by cyclic polypyrroles
have stimulated a large amount of research in the area of
expanded porphyrins.1 A variety of expanded porphyrins
containing up to six pyrrole/heterocyclic rings have been
synthesized, and their properties such as receptors for anions,
ligands for metals, sensitizers for PDT, and as MRI contrast-
ing agents have been exploited recently.2,3 However, only a
few expanded porphyrins containing more than six pyrrole
rings are reported to date. They are the 8 pyrrolic octaphy-
rins,4 the 10 pyrrolic turcasarin,5 the 12 pyrrolic dodecaphy-
rin, and the 16 pyrrolic hexadecaphyrin.6 These macrocycles
are not only interesting from the structural point of view
since they exhibit various nonplanar or figure eight confor-
mations but also for their applications in anion binding and
as catalysts in enantioselective reactions.7 However, all these
macrocycles turned out to be nonaromatic.
Surprisingly, the expanded porphyrins containing seven
and nine pyrrole rings have hitherto escaped all efforts at
their synthesis. Very recently Sessler and co-workers4d were
successful in the synthesis of the nonaromatic 28π hepta-
phyrin [1.0.0.1.0.0.0] 1 by an acid-catalyzed condensation
of tetrapyrrole dialdehyde with bipyrrole, which afforded an
open chain heptapyrrole that upon subsequent cyclization
(4) (a) Vogel, E.; Broring, M.; Fink, J.; Rosen, D.; Schmickler, H.; Lex,
J.; Chan, K. W. K.; Wu, Y.-D.; Plattner, D. A.; Nendel, M.; Houk, K. N.
Angew. Chem., Int. Ed. Engl. 1995, 34, 2511. (b) Broring, M.; Jendrny, J.;
Zander, L.; Schmickler, H.; Lex, J.; Wu, Y.-D.; Nendel, M.; Chen, J.;
Plattner, D. A.; Houk, K. N.; Vogel, E. Angew. Chem., Int. Ed. Engl. 1995,
34, 2515. (c) Werner, A.; Michels, M.; Zander, L.; Lex, J.; Vogel, E. Angew.
Chem., Int. Ed. 1999, 38, 3650. (d) Sessler, J. L.; Seidel, D.; Lynch, V. J.
Am. Chem. Soc. 1999, 121, 11257.
† Indian Institute of Technology.
‡ Alternate e-mail address: tkc@iitk.ac.in.
§ Central Drug Research Institute.
(1) Sessler, J. L.; Gebauer, S. J. In The Porphyrin Handbook, Vol. 2;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New
York, 2000.
(2) (a) Sessler, J. L.; Weghorn, S. J. Expanded, Contracted & Isomeric
Porphyrins, Tetrahedron Organic Chemistry Series, Vol. 15; Pergamon:
New York, 1997. (b) Jasat, A.; Dolphin, D. Chem. ReV. 1997, 97, 2267.
(3) Sessler, J. L.; Hemmi, G.; Mody, T. D.; Murai, T.; Burrell, A. K.;
Young, S. W. Acc. Chem. Res. 1994, 27, 43.
(5) Sessler, J. L.; Weghorn, S. J.; Lynch, V.; Johnson, M. R. Angew.
Chem., Int. Ed. Engl. 1994, 33, 1509.
(6) Setsune, J. L.; Katakami, Y.; Iizuna, N, J. Am. Chem. Soc. 1999,
121, 8957.
(7) Lash, T. D. Angew. Chem., Int. Ed. 2000, 39, 1763.
10.1021/ol000251c CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/03/2000

afforded 1. Inspite of this success, the need to synthesize
other new systems for an understanding of aromaticity, π
Scheme 1
conjugation, and the effect of heteroatom substitution still
remains, and in this Letter, we wish to report the successful
syntheses of three different kinds of heteroatom-containing
meso aryl heptaphyrins, 2, 3, and 4, by an easy and efficient
synthetic methodology. Unlike 1, the heptaphyrins 2, 3, and
4 are aromatic and exhibit inverted structures where one or
two heterocyclic rings have undergone a 180° ring flipping.
porphyrins, sapphyrins and rubyrins, while the tripyrranes
bearing the meso mesityl groups gave an additional product,
which was 30π heptaphyrin. This is probably due to the
increased steric bulk on the meso phenyl ring, which is in
accord with the observation of Setsune and co-workers6 in
the Rothemund reaction of bipyrroles with 2,6-dichlorobenz-
aldehyde. The formation of the heptaphyrin can be rational-
ized by considering the fragmentation of tripyrranes and the
recombination of the fragmented product.9
To synthesize meso aryl heptaphyrins in good yield, a
more rational synthesis was designed with easily available
precursors, either through a [4 + 3] MacDonald type
condensation or through an oxidative coupling reaction. The
key precursors required were hitherto unknown: 5,5′′-bis-
(arylhydroxymethyl)-2,2′:5,2′-terthiophene 6 and 5,14-diphen-
yl-20,21-diselenatetrapyrromethane 7d. 6 was synthesized by
a reaction of terthiophene with n-butyllithium followed by
treatment with aryl/mesityl aldehyde in 75% yield. 7d was
The first clue that the meso aryl heptaphyrins could be
synthesized came from the reaction of mesityl tripyrranes
5a or 5b containing heteroatoms in the presence of 0.3 equiv
of TFA as catalyst in dichloromethane, followed by chloranil
oxidation (Scheme 1). After a basic workup and chromato-
graphic purification, two major products were isolated. They
are 26π rubyrins 8a or 8b in 15% yield and 30π heptaphyrins
2a or 2b in about 2% yield. The formation of trace amounts
of 18π porphyrin and 22π sapphyrin were also noticed. We
have recently shown that modified tripyrranes are not very
stable under the reaction conditions and undergo acid-
catalyzed fragmentation.8 The fragmented products recyclize
to give a mixture of porphyrins and expanded porphyrins.
The tripyrranes bearing the meso phenyl groups gave only
synthesized in 85% yield by a reaction of biselenophene diol
and pyrrole with TFA as the catalyst, using a method similar
to the one reported by us for the synthesis of 7b.10 Thus,
reaction of 6a with 7b, 7c, or 7d with 1 equiv of TFA in
dichloromethane, followed by oxidation with chloranil gave
3b, 3c,
3830
Org. Lett., Vol. 2, No. 24, 2000

or 3d as the only product (yield for 3b is 22%, for 3c is
20%, and for 3d is 15%). 3a was synthesized by reacting
6b and 7a in 20% yield. 3a-3d display a deep purple color
in organic solvents. On protonation with acid, the color
changes immediately to indigo. The heptaphyrins 4a-4d
were synthesized in 15-20% yield through oxidative cou-
pling reactions of 5c or 5d with 7b or 7d in dichloromethane
containing 2 equiv of TFA, where the two pyrrole-pyrrole
links were formed at the final step through R-R coupling.8d
The compositions of the heptaphyrins 2, 3, and 4 were
established from the FAB mass spectra and the analytical
data. The solution structure was arrived at by a detailed
analysis of proton NMR spectra. For the complete assignment
of all the peaks, 2D H,H-Cosy was required. As a represen-
in the H,H-Cosy (Figure 1b). The appearance of individual
doublets for each proton reflects the lower symmetry of the
molecule, and the observation of two doublets in the high-
field region suggested that one of the thiophene rings is
inverted and protons of the inverted ring are experiencing
the ring current of the macrocycle. One can envisage two
possibilities as to which of the thiophene rings is inverted.
They are (a) the central thiophene ring of the terthiophene
unit or (b) one of the terminal thiophenes of the terthiophene
unit or the thiophene ring of the bithiophene unit containing
the ee′ protons. The inversion of the central thiophene ring
containing the aa′ protons is ruled out on the basis of the
symmetry considerations. Such a ring inversion leads to the
presence of a symmetry axis passing through the central S
atom and center of the opposite bithiophene rings containing
the dd′ and ee′ protons, which would result in fewer peaks
in the NMR spectrum than observed. This leads to the
possibility where either of the thiophene rings containing
the cc′ or bb′ protons is inverted and such a ring inversion
would lead to lowering of the symmetry of the molecule
leading to the inequivalence of all the thiophene protons as
observed. The possibility of inversion of thiophene ring
containing ee′ protons is ruled out on the basis of our
previous work on rubyrin and the structure of modified
tripyrromethanes, where the ring inversion was observed in
the tripyrromethane moiety itself.8b Such a ring inversion
has been observed earlier by others11 and us for the
sapphyrins and modified rubyrins containing meso aryl
substituents.8
1
tative example, the H NMR spectra of 3a along with the
correlations observed in H,H-Cosy in the aromatic region
and in the shielded region are shown in Figure 1. There are
The chemical shifts of the inverted thiophene ring protons
were found to be dependent on temperature, and at lower
temperatures these protons are shifted further upfield. A
variable temperature spectral study for these protons for 3d
suggests that the inverted thiophene ring is experiencing a
slow rotation on the NMR time scale, and the further
shielding observed for these protons at lower temperature
suggests that these protons are exposed to the ring current
of the macrocycle. The protonation of the pyrrole nitrogens
by a careful titration of TFA leads to a downfield shift of
pyrrole, thiophene, and bithiophene protons, while the
protons of the inverted ring shift further upfield. For example,
for diprotonated 3d, the inverted ring protons resonate
between -3 to -4 ppm (relative to +0.6 to -0.75 ppm for
the free base) and the NH protons resonate as two individual
singlets in the region -4 to -5 ppm. This observation
suggests that upon protonation the inverted ring becomes
more planar and feels the effect of the ring current of the
macrocycle. The ∆d values (the chemical shift difference
Figure 1. 1H NMR spectrum of 3a in CDCl3: (a) in the aromatic
region. The inset shows the high-field region. (b) 2D H,H-Cosy in
the aromatic and the shielded region. The correlations are shown
by dotted lines.
(8) (a) Narayanan, S. J.; Sridevi, B.; Chandrashekar, T. K.; Vij, A.; Roy,
R. Angew. Chem., Int. Ed. 1998, 37, 3394. (b) Narayanan, S. J.; Sridevi,
B.; Chandrashekar, T. K.; Vij, A.; Roy, R. J. Am. Chem. Soc. 1999, 121,
9053. (c) Srinivasan, A.; Mahajan, S.; Pushpan, S. K.; Kumar, M. R.;
Chandrashekar, T. K. Tetrahedron Lett. 1998, 39, 1961. (d) Narayanan, S.
J.; Sridevi, B.; Chandrashekar, T. K.; Englich, U.; Senge, K. R. Org. Lett.
1999, 1, 587.
(9) Lash, T. D.; Chaney, S. T.; Ritcher, D. T. J. Org. Chem. 1998, 63,
9076.
(10) Srinivasan, A.; Pushpan, S. K.; Kumar, M. R.; Chandrashekar, T.
K.; Roy, R. Tetrahedron 1999, 55, 6671.
10 â-CH protons on the thiophene rings. Eight of them (aa′,
bb′, dd′, and ee′) resonate in the aromatic region between
9.2 and 10.2 ppm, and the remaining two protons (cc′) appear
as two doublets in the shielded region between -0.5 to -1.5
ppm. The pyrrole protons (ff′ and gg′) also appear as
individual doublets in the region 8.5 to 8.2 ppm. These
assignments were made on the basis of the correlation seen
(11) Latos-Graznyski, L.; Rachlewicz, K. Chem. Eur. J. 1995, 1, 68. (b)
Sessler, J. L.; Seidel, D.; Bucher, C.; Lynch, V. J. Chem. Soc., Chem.
Commun. 2000, 1473.
Org. Lett., Vol. 2, No. 24, 2000
3831

between the inner and the outer protons) for the protonated
derivatives vary in the range 13-17 ppm (for example, for
3b, 16.6 ppm; 3c, 15.9 ppm; 3d, 15.8 ppm), clearly
suggesting the aromatic nature of the heptaphyrins and also
accounting for the presence of 30π electrons according to
the 4n + 2 rule. To the best of our knowledge these are the
first examples of meso aryl expanded porphyrins containing
seVen heterocyclic rings haVing an inVerted structure and
displaying aromaticity.
comparison of these values with the corresponding rubyrins
shows red shift of absorption bands, in agreement with the
extended conjugation.8b These absorption bands are also red
shifted relative to 1, reflecting the effect of heteroatom
substitution. The ꢀ value of the free base form is about six
times higher than that observed for 1. Protonation by addition
of a dilute solution of TFA in dichloromethane leads to
further red shifting of the Soret and Q-bands; this effect is
typical of meso tetra aryl porphyrins.8 Additional evidence
for the aromatic character comes from the preliminary cyclic
voltametric studies. 3b and 3d exhibit two reversible
reductions and two irreversible oxidations. A comparison of
these data with corresponding tetra aryl porphyrin suggests
the stabilization of LUMO’s of 3b and 3d by 440 and 470
mV, respectively. An estimated HOMO-LUMO gap of
1.29V for 3b and 1.38V for 3d indicates a significant
reduction relative to meso aryl rubyrin and sapphyrin (for
sapphyrin it is -1.88 V and for rubyrin it is -1.64 V), thus
explaining large red shifts observed in the electronic
spectrum.8a
Further proof of the aromaticity comes from the electronic
absorption spectral studies. The spectra for free base and
protonated forms of 3b shown in Figure 2 indicates the
In conclusion, we have successfully synthesized the first
examples of aromatic meso aryl 30π heptaphyrins which
exhibit three different types of inverted structures.
Acknowledgment. T.K.C. is grateful to the Department
of Science and Technology, New Delhi, India, for financial
support of this work. S.K.P. thanks CSIR for a Senior
Research Fellowship.
Supporting Information Available: Tables of UV-vis
Figure 2. Electronic absorption spectra of 4.46 × 10-6 M 3b (s)
and its dication (‚‚‚‚‚) in dichloromethane.
1
absorption data, H NMR spectra, CV, mass spectra, and
1
temperature-dependent H NMR spectra in freebase and
protonated forms for selected compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
presence of intense Soret type bands in the region 560-570
nm and four Q-bands in the region of 750-1100 nm. A
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