Synthesis, spectroscopy, and reactivity of meso-unsubstituted azuliporphyrins and their heteroanalogues. Oxidative ring contractions to carba-, oxacarba-, thiacarba-, and selenacarbaporphyrins

Article abstract of DOI:10.1021/jo0402531

This paper reports the first detailed study on meso-unsubstituted azuliporphyrins, an important family of porphyrin-like molecules where one of the usual pyrrole rings has been replaced by an azulene subunit. Although the azulene moiety introduces an elem

Full text of DOI:10.1021/jo0402531

Synthesis, Spectroscopy, and Reactivity of meso-Unsubstituted
Azuliporphyrins and Their Heteroanalogues. Oxidative Ring
Contractions to Carba-, Oxacarba-, Thiacarba-, and
Selenacarbaporphyrins†
Timothy D. Lash,* Denise A. Colby, Shelley R. Graham, and Sun T. Chaney
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160
tdlash@ilstu.edu
Received August 23, 2004
This paper reports the first detailed study on meso-unsubstituted azuliporphyrins, an important
family of porphyrin-like molecules where one of the usual pyrrole rings has been replaced by an
azulene subunit. Although the azulene moiety introduces an element of cross-conjugation,
zwitterionic resonance contributors with tropylium and carbaporphyrin substructures give azuli-
porphyrins diatropic character that falls midway between true carbaporphyrins and nonaromatic
benziporphyrins. Protonation affords an aromatic dication where this type of resonance interaction
is favored due to the associated charge delocalization. Two different “3 + 1” syntheses of meso-
unsubstituted azuliporphyrins have been developed. Acid-catalyzed reaction of readily available
tripyrrane dicarboxylic acids with 1,3-azulenedicarbaldehyde, followed by oxidation with DDQ or
FeCl3, affords good yields of azuliporphyrins. Alternatively, azulene reacted with acetoxymethyl-
pyrroles (2 equiv) in refluxing acetic acid/2-propanol to give tripyrrane analogues, and following a
deprotection step, condensation with a pyrrole dialdehyde in TFA-CH2Cl2 gave the azuliporphyrin
system. The latter approach was also used to prepare 23-thia- and 23-selenaazuliporphyrins.
However, reaction of the azulitripyrrane with 2,5-furandicarbaldehyde produced a mixture of three
oxacarbaporphyrins in moderate yield. The free base forms of thia- and selenaazuliporphyrins both
showed intermediary aromatic character that was considerably enhanced upon protonation. The
UV-vis spectra for azuliporphyrins and their heteroanalogues showed four bands between 350
and 500 nm and broad absorptions at higher wavelengths. Addition of TFA gave dications that
showed porphyrin-like spectra with Soret bands between 460 and 500 nm. In the presence of
pyrrolidine, azuliporphyrins and their heteroanalogues undergo nucleophilic attack on the seven-
membered ring to give carbaporphyrin adducts. These systems also undergo oxidative rearrange-
ments under basic conditions with t-BuOOH to give benzocarbaporphyrins. The selenaazulipor-
phyrin afforded two benzoselenacarbaporphyrins, a previously unknown core-modified carbaporphyrin
system. The proton NMR spectra for these compounds showed strong diatropic ring currents with
the internal CH resonance upfield above -5 ppm, while the meso-protons resonated downfield near
10 ppm. The UV-vis spectra were also porphyrin-like and gave strong Soret bands at ca. 440 nm.
Introduction
als,4 and components of molecular-based information
storage systems.5 Furthermore, porphyrins and related
synthetic pigments have medicinal applications and are
being used as photosensitizers in photodynamic therapy.6
Analogues of the porphyrins are also being increasingly
studied, partially due to the expectation that these
systems will also possess useful applications.7-12 Core-
The porphyrins have attracted the interest of organic
chemists for over 100 years due to their widespread
occurrence in nature.1 These “Pigments of Life” fulfill
many roles ranging from oxygen transportation (hemo-
globin), electron transfer (cytochromes), and oxidations
and reductions (peroxidase, catalase, cytochrome oxidase)
to light harvesting and photosynthesis (chlorophylls).1
Synthetic porphyrins have also been investigated for
numerous applications including the production of mo-
lecular wires,2 oxidation catalysts,3 novel optical materi-
(2) Crossley, M. J.; Burn, P. L. J. Chem Soc., Chem. Commun. 1991,
1569.
(3) Ostovic, D.; Bruice, T. C. Acc. Chem. Res. 1992, 25, 314.
(4) Fabian, J.; Nakazumi, H.; Matsuoka, M. Chem. Rev. 1992, 92,
1197.
(5) Liu, Z.; Yasseri, A. A.; Lindsey, J. S.; Bocian, D. F. Science 2003,
302, 1543.
* To whom correspondence should be addressed.
† Conjugated Macrocycles Related to the Porphyrins. 38. For part
37, see: Richter, D. T.; Lash, T. D. J. Org. Chem. 2004, 69, in press
8842-8850.
(1) The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Academic Press: San Diego, 2000; Vols. 1-10; 2003; Vols.
11-20.
(6) (a) Pandey, R. K.; Zheng, G. In The Porphyrin Handbook; Kadish,
K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego,
2000; Vol. 6, pp 157-230. (b) Bonnett, R. Chem. Soc. Rev. 1995, 24,
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(7) Vogel, E. J. Heterocycl. Chem. 1996, 33, 1461.
(8) Sessler, J. L. J. Porphyrins Phthalocyanines 2000, 4, 331.
10.1021/jo0402531 CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/06/2004
J. Org. Chem. 2004, 69, 8851-8864
8851

Lash et al.
CHART 1
modified porphyrins where one or more of the nitrogen
atoms have been replaced by oxygen, nitrogen, selenium,
or tellurium have been known since the late 1960s,13 and
these systems show unique coordination chemistry12 as
well as some promise as photosensitizers.14 Carbapor-
phyrinoid systems, porphyrin analogues where one or
more of the pyrrole units have been replaced by carbocy-
clic rings, were first investigated in the mid-1990s.10,11,15-21
These relatively new porphyrin-like macrocycles show
somewhat more divergent chemistry, including the for-
mation of stable organometallic derivatives21-27 and
unprecedented oxidation reactions.28,29
Azuliporphyrins 1 (Chart 1) are a particularly interest-
ing group of carbaporphyrinoids that incorporate an
azulene subunit.30 These porphyrin analogues show some
overall aromatic character, but this is diminished com-
pared to similar carbaporphyrinoid systems such as
oxybenziporphyrins (2),15 tropiporphyrins (3),16 and ben-
zocarbaporphyrins (4)17 due to cross-conjugation inter-
rupting the 18π electron delocalization pathway. Azuli-
porphyrins have been shown to exhibit rich and unusual
chemistry29,31 and readily form organometallic derivatives
with nickel(II), palladium(II), or platinum(II) salts.25
Although the first synthesis of an azuliporphyrin was
published in 1997,30a details on the synthesis and spec-
troscopic properties of these intriguing porphyrinoids and
related core-modified systems have not previously been
available. In this paper, syntheses of meso-unsubstituted
azuliporphyrins by two different “3 + 1” methodologies
are reported, and this chemistry has also been applied
to the preparation of related 23-thia- and 23-selenaazu-
liporphyrins.30 In addition, oxidative ring contractions are
shown to give carbaporphyrins, 23-oxacarbaporphyrins,
23-thiacarbaporphyrins, and 23-selenacarbaporphyrins.
These studies provide the foundations for future studies
in this area of porphyrin analogue chemistry.30,32
(9) (a) Sessler, J. L.; Gebauer, A.; Vogel, E. In The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
Press: San Diego, 2000; Vol. 2, pp 1-54. (b) Sessler, J. L.; Seidel, D.
Angew. Chem., Int. Ed. 2003, 42, 5134.
(10) Lash, T. D. Synlett 2000, 279.
(11) Lash, T. D. In The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 2, pp
125-199.
(12) Latos-Grazynski, L. In The Porphyrin Handbook; Kadish, K.
M., Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego, 2000;
Vol. 2, pp 361-416.
(13) Johnson, A. W. In Porphyrins and Metalloporphyrins; Smith,
K. M., Ed.; Elsevier: Amsterdam, 1975; pp 729-754.
(14) Hilmey, D. G.; Abe, M.; Nelen, M. I.; Stilts, C. E.; Baker, G. A.;
Baker, S. N.; Bright, F. V.; Davies, S. R.; Gollnick, S. O.; Oseroff, A.
R.; Gibson, S. L.; Hilf, R.; Detty, M. R. J. Med. Chem. 2002, 45, 449.
(15) (a) Lash, T. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2533.
(b) Lash, T.D.; Chaney, S. T.; Richter, D. T. J. Org. Chem. 1998, 63,
9076. (c) Richter, D. T.; Lash, T. D. Tetrahedron 2001, 57, 3659.
(16) Lash, T. D.; Chaney, S. T. Tetrahedron Lett. 1996, 37, 8825.
(17) (a) Lash, T. D.; Hayes, M. J. Angew. Chem., Int. Ed. Engl. 1997,
36, 840. (b) Lash, T. D.; Hayes, M. J.; Spence, J. D.; Muckey, M. A.;
Ferrence, G. M.; Szczepura, L. F. J. Org. Chem. 2002, 67, 4860. (c)
Liu, D.; Lash, T. D. J. Org. Chem. 2003, 68, 1755.
Results and Discussion
“3 + 1” Syntheses of Azuliporphyrins. The full
potential of the “3 + 1” variant of the MacDonald
condensation for porphyrin synthesis had not been ap-
preciated until the mid-1990s.33-37 This route involves
the condensation of a tripyrrane (e.g., 5, Scheme 1) with
pyrrole dialdehydes to afford, following an oxidation step,
the corresponding porphyrin products.33 This approach
is ideally suited for the synthesis of porphyrin analogues
with one exotic subunit replacing a pyrrole ring because
simple aromatic dialdehydes can be reacted with readily
available tripyrranes to give macrocyclic products.10,11
Hence, reaction of tripyrranes with 4-hydroxybenzene-
1,3-dicarbaldehyde affords oxybenziporphyrins 2,15 1,3,5-
cycloheptatriene-1,6-dicarbaldehyde gives tropiporphy-
(18) (a) Berlin, K.; Steinbeck, C.; Breitmaier, E. Synthesis 1996, 336.
(b) Berlin, K. Angew. Chem. Int. Ed. Engl. 1996, 35, 1820.
(19) Hayes, M. J.; Lash, T. D. Chem. Eur. J. 1998, 4, 508.
(20) Lash, T. D.; Romanic, J. L.; Hayes, M. J.; Spence, J. D. Chem.
Commun. 1999, 819.
(21) Miyake, K.; Lash, T. D. Chem. Commun. 2004, 178.
(22) Muckey, M. A.; Szczepura, L. F.; Ferrence, G. M.; Lash, T. D.
Inorg. Chem. 2002, 41, 4840.
(23) Lash, T. D.; Colby, D. A.; Szczepura, L. F. Inorg. Chem. 2004,
43, 5258.
(24) Lash, T. D.; Rasmussen, J. M.; Bergman, K. M.; Colby, D. A.
Org. Lett. 2004, 6, 549.
(32) These results were presented, in part, at the following meet-
ings: (a) 213th National ACS Meeting, San Francisco, California, April
1997 (Chaney, S. T.; Lash, T. D. Book of Abstracts, ORGN 15). (b) 30th
Great Lakes Regional American Chemical Society Meeting, Loyola
University, Chicago IL, May 1997 (Chaney, S. T.; Lash, T. D. Program
and Abstracts, Abstract No. 127). (c) 5th Chemical Congress of North
America, Cancun, Mexico, Nov 1997 (Lash, T. D.; Chaney, S. T.; Hayes,
M. J.; Petryka, J. C.; Richter, D. T. Book of Abstracts, Abstract No.
1154). (d) 221st National ACS Meeting, San Diego, CA, April 2001
(Graham, S. R.; Lash, T. D. Book of Abstracts, ORGN 186).
(33) Lash, T. D. Chem. Eur. J. 1996, 2, 1197.
(25) (a) Graham, S. R.; Ferrence, G. M.; Lash, T. D. Chem. Commun.
2002, 894. (b) Lash, T. D.; Colby, D. A.; Graham, S. R.; Ferrence, G.
M.; Szczepura, L. F. Inorg. Chem. 2003, 42, 7326.
(26) Stepien, M.; Latos-Grazynski, L.; Lash, T. D.; Szterenberg, L.
Inorg. Chem. 2001, 40, 6892.
(27) (a) Stepien, M.; Latos-Grazynski, L. Chem. Eur. J. 2001, 7,
5113. (b) Stepien, M.; Latos-Grazynski, L.; Szterenberg, L.; Panek, J.;
Latajka, Z. J. Am. Chem. Soc. 2004, 126, 4566. (c) Szymanski, J. T.;
Lash, T. D. Tetrahedron Lett. 2003, 44, 8613.
(28) (a) Hayes, M. J.; Spence, J. D.; Lash, T. D. Chem. Commun.
1998, 2409. (b) Lash, T. D.; Muckey, M. A.; Hayes, M. J.; Liu, D.;
Spence, J. D.; Ferrence, G. M. J. Org. Chem. 2003, 68, 8558.
(29) Colby, D. A.; Ferrence, G. M.; Lash, T. D. Angew. Chem., Int.
Ed. 2004, 43, 1346.
(34) (a) Lin, Y.; Lash, T. D. Tetrahedron Lett. 1995, 36, 9441. (b)
Chandrasekar, P.; Lash, T. D. Tetrahedron Lett. 1996, 37, 4873.
(35) Lash, T. D. J. Porphyrins Phthalocyanines 1997, 1, 29.
(36) (a) Boudif, A.; Momenteau, M. J. Chem. Soc., Chem. Commun.
1994, 2069. (b) Boudif, A.; Momenteau, M. J. Chem. Soc., Perkin Trans.
1 1996, 1235.
(30) Preliminary communications: (a) Lash, T. D.; Chaney, S. T.
Angew. Chem., Int. Ed. 1997, 36, 839. (b) Graham, S. R.; Colby, D. A.;
Lash, T. D. Angew. Chem., Int. Ed. 2002, 41, 1371.
(37) Sessler, J. L.; Genge, J. W.; Urbach, A.; Sanson, P. Synlett 1996,
187.
(31) Lash, T. D. Chem. Commun. 1998, 1683.
8852 J. Org. Chem., Vol. 69, No. 25, 2004

Reactivity of Azuliporphyrins and Their Heteroanalogues
SCHEME 1
SCHEME 2
SCHEME 3
rins 3,16 and 1,3-indenedicarbaldehyde yields benzo-
carbaporphyrins 4 (Chart 1).17 These aromatic porphy-
rinoids all show large diatropic ring currents in their
proton NMR spectra where the internal CH resonates
near -7 ppm. They can also act as trianionic ligands and
afford stable silver(III) derivatives.22-24 Azulene readily
undergoes electrophilic substitution at the 1 and 3
positions and reacts with POCl3-DMF under Vilsmeier-
Haack conditions at 85 °C to give the diformylazulene
6.38 The 1,3-orientation of the two aldehyde groups
provides the correct geometry to generate a carbapor-
phyrinoid macrocycle. Reaction of 6 with tripyrranes 5
was accomplished with TFA in dichloromethane, and
subsequent oxidation with DDQ or aqueous ferric chlo-
ride solutions39,40 afforded the macrocyclic products 1
(Scheme 1). Column chromatography commonly gave a
brown prefraction that appeared to consist of highly
impure benzocarbaporphyrin byproducts, and the azuli-
porphyrins eluted as the solvent polarity was increased
as deep green colored bands. Recrystallization was ac-
complished from chloroform-hexanes and gave the azu-
liporphyrins as dark green or purple crystals. The
azuliporphyrins were only sparingly soluble in organic
solvents, and this led to some difficulties in characterizing
the free base forms of these porphyrinoids. However,
these molecules retained a plane of symmetry by proton
NMR spectroscopy, and this indicates that the NH is
either favored at position 23 or that the tautomers 1 and
1′ are in rapid equilibrium. The decreased steric interac-
tion between the internal CHs in tautomer 1, together
with the increased potential for hydrogen-bonding inter-
actions, most likely favors this form, and this supposition
is supported by DFT studies.41 We also attempted to
synthesize azuliporphyrins from commercially available
guaiazulene (7). Formylation of 7, followed by oxidation
with DDQ, affords the substituted dialdehyde 8 (Scheme
2).42 The presence of two alkyl substituents on the
azulene ring could potentially increase the solubility of
the resulting azuliporphyrins. However, all attempts to
react 8 with tripyrrane 5a failed to give the required
porphyrinoid products possibly due to steric interference
from the 4-methyl substituent.
During the course of these early investigations, parallel
studies were being carried out by Breitmeier and co-
workers.18a In this work, dialdehyde 6 was reacted with
tripyrrane 5a in the presence of HBr, and the macrocyclic
products were oxidized with DDQ (Scheme 3). These
conditions afforded complex mixtures of benzocarbapor-
phyrins 4 and 9, and no azuliporphyrin formation was
noted in this study.18a Further investigations by our
group subsequently showed that this type of rearrange-
ment occurs readily under oxidative conditions (see
below).31 On the other hand, benzocarbaporphyrins are
far more easily synthesized by the reaction of tripyrranes
5 with 1,3-diformylindene, and this direct route also
avoids the formation of porphyrinoid mixtures.17
Although the “3 + 1” approach provides a convenient
route to azuliporphyrins, this chemistry is less well suited
to the preparation of further modified porphyrinoids with
two or more exotic rings. To overcome some of these
limitations, the synthesis of a tripyrrane-like system 10
with a central azulene moiety was investigated (Scheme
4).30b Tripyrranes are usually prepared by reacting an
R-unsubstituted pyrrole with 2 equiv of an acetoxymeth-
ylpyrrole under acidic conditions. This chemistry relies
upon the propensity for pyrrole to undergo electrophilic
substitution at its R-positions, and indeed, the key
carbon-carbon bond-forming steps in most porphyrin
syntheses rely upon this property. As azulene favors
electrophilic substitution at the equivalent 1,3-positions
(Chart 2), we speculated that it might be possible to
prepare azulitripyrranes 10 by reacting azulene with
acetoxymethylpyrroles 11. Using mild acidic conditions
(refluxing acetic acid/2-propanol), azulene was found to
react with 2 equiv of 11a or 11b to give good yields of
the required tripyrrane analogues. The dibenzyl ester
(38) Hafner, K.; Bernhard, C. Liebigs Ann. Chem. 1959, 625, 108.
(39) Lash, T. D.; Richter, D. T.; Shiner, C. M. J. Org. Chem. 1999,
64, 7973.
(40) Richter, D. T.; Lash, T. D. Tetrahedron Lett. 1999, 40, 6735.
(41) Ghosh, A.; Wondimagegn, T.; Nilsen, H. J. J. Phys. Chem. B
1998, 102, 10459.
(42) Okajima, T.; Kurokawa, S. Chem. Lett. 1997, 69.
J. Org. Chem, Vol. 69, No. 25, 2004 8853

Lash et al.
SCHEME 4
SCHEME 5
CHART 2
10a precipitates from solution to give a blue powder. The
residues were then subjected to column chromatography,
and three blue bands were observed corresponding to
residual azulene, pyrrolylmethylazulene 12 and azu-
litripyrrane 10a. Further recrystallization of the third
fraction gave 10a as blue crystals in a total yield of 73%.
When azulene was reacted with 1 equiv of 11a, the
monosubstituted azulene 12 was isolated as the major
product. Although the chemistry of 12 is not a topic for
this paper, this structure also clearly has potential value
in porphyrin analogue synthesis. Reaction of azulene
with 2 equiv of tert-butyl ester 11b gave azulitripyrrane
10b in 59% yield. This product failed to give clear
banding on the column, as had been the case for 10a,
but could be isolated reproducibly in pure form. Attempts
to cleave the benzyl ester protective groups from 10a by
hydrogenolysis over 10% Pd/C under conventional condi-
tions failed to give the corresponding dicarboxylic acid,
and for this reason all of the subsequent studies were
performed using the di-tert-butyl ester 10b.
To test the utility of 10b in macrocycle formation, a
“back-to-front” synthesis of the azuliporphyrin system
was investigated (Scheme 5). The tripyrrane analogue
was initially treated with TFA at room temperature for
10 min to cleave the tert-butyl ester protective groups,
and then the solution was diluted with dichloromethane
and pyrrole dialdehyde 13a was added. After the mixture
was stirred under nitrogen for 2 h, the solution was
neutralized with triethylamine and oxidized with DDQ.
Following chromatography and recrystallization from
chloroform-hexanes, azuliporphyrin 14a was isolated in
36% yield. This product is an isomer of azuliporphyrin
1a, and apart from minor differences in the proton NMR
spectra, these two compounds are virtually indistinguish-
able. Reaction of 10b with 2,5-thiophenedicarbaldehyde
(13b) similarly afforded the thiaazuliporphyrin 14b,
while diformylselenophene 13c gave the related selena-
azuliporphyrin 14c. For the core-modified azuliporphy-
rins, the best results were obtained using 0.1% aqueous
ferric chloride solutions as the oxidant, and 14b and 14c
were isolated in 45% and 27% yields, respectively.
Interestingly, 2,5-furandicarbaldehyde (13d) failed to
give any isolatable oxaazuliporphyrin 14d, although the
oxacarbaporphyrins 15a-c were isolated in moderate
yield instead. Furan-containing porphyrinoids of this type
are relatively basic and cannot be isolated as the free base
structures.43 Instead, the solutions are washed with
dilute hydrochloric acid and the products isolated as the
corresponding hydrochloride salts. A related oxacarba-
porphyrin has been synthesized from a furan-containing
tripyrrane analogue and diformyl indene, and this system
has been fully characterized previously.43 For this reason,
the properties of 15a-c will not be discussed in detail.
However, it is worth noting that these porphyrinoids
show strong diatropic ring currents by proton NMR
spectroscopy and the interior CH resonates between -6.4
and -6.8 ppm for solutions in CDCl3. The UV-vis spectra
for the free base forms in 5% Et3N-chloroform closely
resembles porphyrin-type chromophores. Oxacarbapor-
phyrin 15a shows a Soret band at 430 nm, together with
a series of four “Q-bands” at 522, 555, 620, and 681 nm.
Oxacarbaporphyrins have been shown to be superior
organometallic ligands forming stable nickel(II), palla-
dium(II), and platinum(II) derivatives.43 Azulitripyrrane
10b has also been used to synthesize a dicarbaporphy-
rinoid system,30b but full details of this study will be
reported elsewhere.
These routes to azuliporphyrins are straightforward
and versatile and are starting to see application by other
research groups. Recently, Chandrashekar and co-work-
ers have prepared two core-modified azuliporphyrins 1644
by reacting 6 with dimesityltripyrranes 17 under the
conditions developed by our group for the synthesis of
(43) (a) Liu, D.; Lash, T. D. Chem. Commun. 2002, 2426. (b) Liu,
D.; Ferrence, G. M.; Lash, T. D. J. Org. Chem. 2004, 69, 6079.
8854 J. Org. Chem., Vol. 69, No. 25, 2004

Reactivity of Azuliporphyrins and Their Heteroanalogues
SCHEME 6
SCHEME 7
FIGURE 1. UV-vis spectra of diphenylazuliporphyrin 1b.
Dotted line: free base in 5% Et3N-chloroform. Bold line:
dication in 5% TFA-chloroform.
CHART 3a
etioazuliporphyrins 1a-c (Scheme 6). In addition, the
same approach has been applied to the preparation of a
tribenzoazuliporphyrin by Okujima et al.45 We have also
developed a one-pot route to tetraarylazuliporphyrins 18
using Rothemund-type chemistry under Lindsey’s boron
trifluoride etherate catalyzed conditions (Scheme 7).46
This has made it possible to conduct parallel studies on
the chemistry of meso-unsubstituted and meso-tetrasub-
stituted systems that parallels research into true por-
phyrins. This approach has been particularly useful for
investigations into the metalation of azuliporphyrins25
and related benzocarbaporphyrins.22,23
Aromatic Character, Protonation, and Solvent
Effects. The UV-vis spectra of azuliporphyrins 1 show
a distinctive set of four bands between 350 and 500 nm
followed by a broad band that extends over most of the
remaining visible region (Figure 1). These spectra are
quite different from the spectra obtained for porphyrins
or aromatic carbaporphyrinoids such as oxybenziporphy-
rins 2 or benzocarbaporphyrins 4 (Chart 1) which show
a strong Soret band near 400 nm and a series of minor
Q-bands at longer wavelengths.15,17 This suggests that
the azuliporphyrin system is electronically quite different
from true porphyrins, a property that we attribute to the
presence of a cross-conjugated azulene ring. The proton
NMR spectra for azuliporphyrins 1a-c also confirm the
reduced aromatic character for this system compared to
carbaporphyrinoids 2-4.15-17 For benzocarbaporphyrins
4, the external meso-protons give rise to two 2H singlets
near 10 ppm,17 but the equivalent resonances for 1c show
a Selected chemical shift values from the proton NMR spectra
of benzocarbaporphyrin 4 and benziporphyrin 19. The aromatic
porphyrinoid shows a ∆δ between the internal and external
protons of nearly 17 ppm, but the overall nonaromatic benzipor-
phyrin shows no significant difference between the chemical shifts
for the internal and external benzene protons.
up at 8.9 and 9.2 ppm. Significant problems arise in
analyzing the spectra for the free base azuliporphyrins
as they have poor solubility characteristics and aggregate
in solution. Traces of water seem to decrease the ag-
gregation and improve the quality of the spectra in some
cases. The internal CH is difficult to assign because this
resonance falls into a region obscured by solvent impuri-
ties, and this is particularly problematic for poorly soluble
samples of this type. However, azuliporphyrin 1c gives
the best solubility characteristics and produces a broad
1H resonance at 1.8 ppm in anhydrous CDCl3 that was
distilled from calcium hydride. These results indicate that
azuliporphyrins has some aromatic character. While
benzocarbaporphyrin shows the internal CH at ca. -7
ppm, the overall nonaromatic benziporphyrin system 19
shows the equivalent resonance at +7.9 ppm (Chart 3).15b
The meso-protons for 19 are also present at 6.6 and 7.3
ppm.15b Therefore, azuliporphyrins seem to fall into an
intermediary region that falls far short of the strongly
aromatic character demonstrated by 2 and 4. These
properties are attributed to dipolar resonance contribu-
tors such as 20 that can be generalized with the hybrid
structure 20′ (Chart 4). The seven-membered ring can
donate electron density, thereby taking on tropylium-type
character while producing an 18π electron delocalization
pathway within the macrocycle. This produces two
aromatic subunits, which is clearly beneficial, but these
(44) Venkatraman, S.; Anand, V. G.; PrabhuRaja, V.; Rath, H.;
Sankar, J.; Chandrashekar, T. K.; Teng, W.; Senge, K. R. Chem.
Commun. 2002, 1662.
(45) Okujima, T.; Komobuchi, N.; Shimizu, Y.; Uno, H.; Ono, N.
Tetrahedron Lett. 2004, 45, 5461.
(46) (a) Colby, D. A.; Lash, T. D. Chem. Eur. J. 2002, 8, 5397. (b)
Lash, T. D.; Colby, D. A.; Ferrence, G. M. Eur. J. Org. Chem. 2003,
4533.
J. Org. Chem, Vol. 69, No. 25, 2004 8855

Lash et al.
CHART 4
dipolar canonical forms are limited due to the require-
ment for charge separation. Some interesting differences
in the chemical shifts can be seen due to solvent, although
low solubility restricts this type of investigation. In C6D6,
azuliporphyrin 1c was sufficiently soluble to give a proton
NMR spectrum. The meso-protons were observed at 7.9
and 8.8 ppm, compared to 7.9 and 8.9 ppm in CDCl3,
while the doublet for the azulene protons nearest to the
macrocycle shifted upfield from 9.2 ppm in CDCl3 to 8.8
ppm in C6D6. These results suggest that the azulipor-
phyrin system has a slightly decreased macrocyclic ring
current in C6D6 compared to CDCl3, possibly due to a
lesser degree of stabilization to the dipolar contributors
in the less polar hydrocarbon solvent. Pyridine would be
expected to stabilize the dipolar resonance contributors
and lead to enhanced diatropic character. This appears
to be the case, as the meso-protons for 1c in C5D5N
resonate at 8.3 and 9.4 ppm, while the 2H azulene
doublet appears at 9.6 ppm. Unfortunately, the internal
CH could not be observed in these studies, although
similar trends were obtained for thia- and selenaazuli-
porphyrins 14b and 14c. It is worth noting that meso-
tetraphenylazuliporphyrin 18 gives the internal CH
resonance at +3.2 ppm, but in this case the phenyl groups
are likely to decrease the planarity of the macrocycle due
to steric interactions and this provides an explanation
for the observed downfield shift of this resonance com-
pared to 1c.
Azuliporphyrins readily protonate to give the corre-
sponding dications 21 (Chart 4). The UV-vis spectrum
of 1b in TFA-chloroform is far more porphyrin-like
showing two strong Soret-like bands at 368 and 466 nm
and more defined Q-type bands at higher wavelengths
(Figure 1). Electron-donation from the cycloheptatriene
ring can now aid in charge delocalization, and this more
strongly favors a combination of tropylium and carba-
porphyrin character in the dications. This leads to a
pronounced increase in the diatropic ring current for the
diprotonated species. For instance, the 400 MHz proton
NMR spectrum of diphenylazuliporphyrin 1b in TFA-
CDCl3 shows the internal CH at -3 ppm, while the NHs
resonate between 0 and -2 ppm (Figure 2). The meso-
protons are shifted downfield giving two 2H singlets at
FIGURE 2. Partial 400 MHz proton NMR spectrum of
diphenylazuliporphyrin 1b in TFA-CDCl3. This spectrum
corresponds to the aromatic dication.
9.6 and 10.5 ppm, while the 2H azulene doublet is also
downfield at 10.0 ppm.
Core-modified azuliporphyrins 14b and 14c show
many of the same characteristics exhibited by 1a-c. The
UV-vis spectrum for thiaazuliporphyrin 14b in 5%
Et3N-chloroform also shows four bands in the near-UV
and blue regions at λmax values of 372, 384, 448, and 477
nm, followed by broad absorptions between 500 and 800
nm. Selenaazuliporphyrin 14c gave four defined bands
at 363, 399, 449, and 476 nm, again followed by broad
ill-defined absorptions at longer wavelengths. The spectra
are all superficially similar, although the first two bands
in the UV-vis spectrum for 14b are starting to merge
together. The proton NMR spectrum for 14b in CDCl3
showed the meso-protons downfield at 9.0 and 9.2 ppm,
suggesting a slightly increased diatropic character, while
the thiophene protons gave a singlet at 8.8 ppm and the
azulene doublet was present at 9.5 ppm. However, the
internal CH could be identified at 2.8 ppm, a value that
is significantly downfield from the broad resonance
observed for 1c. In C6D6, the meso-protons resonated at
8.8 and 9.1 ppm, while the thiophene ring gave a 2H
singlet at 8.5 ppm and the azulene doublet appeared at
8.9 ppm. In pyridine-d5, the equivalent resonances were
observed at 9.4, 9.8, 9.1, and 10.0 ppm, respectively.
These values suggest that the diatropic character arising
from dipolar resonance contributors is slightly enhanced
in pyridine and slightly diminished in benzene. Unfor-
tunately, the low solubility of 14b in C6D6 prevented us
from identifying the internal CH resonance. In C5D5N,
the internal CH gave a 1H singlet at 3.2 ppm which
seemingly contradicts the trends observed for the exter-
nal protons. In the proton NMR spectrum for selenaa-
zuliporphyrin 14c in CDCl3 (Figure 3), the two 2H meso-
resonances were observed near 9.2 ppm, while the
selenophene unit gave a 2H singlet at 8.9 and the azulene
21,31-protons produced a 2H doublet at 9.5 ppm. In
8856 J. Org. Chem., Vol. 69, No. 25, 2004

Reactivity of Azuliporphyrins and Their Heteroanalogues
SCHEME 8
at 385 nm. The selenophene analogue 14c shows a strong
band at 494 nm and two weak bands near 380 nm. The
UV-vis spectra for the dications derived from 1, 14b,
and 14c show an increasing dominance for the stronger
Soret-like band compared to the other absorptions going
from NH to S to Se. The proton NMR spectra for 14b
and 14c in TFA-CDCl3 show strong ring currents with
the internal CH at -3.4 ppm for 14b and -2.6 ppm for
14c. The small difference between these values does not
seem to be significant as the chemical shift values for
the external protons are comparable. Carbon-13 NMR
spectra for 13b and 13c confirm the presence of a plane
of symmetry in these macrocycles.
FIGURE 3. 400 MHz proton NMR spectra of selenaazulipor-
phyrin 14c. The lower spectrum was run in CDCl3. The small
broad peak near 3 ppm corresponds to the internal CH, while
the three singlets around 9 ppm represent the selenophene
and meso-protons. The upper spectrum corresponds to 14c in
pyridine-d5. The external protons are significantly shifted
downfield, suggesting an increased macrocyclic ring current,
but the internal CH is also shifted downfield and gives a sharp
singlet at 3.4 ppm.
CHART 5
Nucleophilic Additions and Oxidative Ring Con-
tractions. Azuliporphyrins are susceptible to nucleo-
philic attack onto the electron-deficient cycloheptatriene
ring, and this reactivity may play a role in the oxidative
ring contraction of azuliporphyrins to afford benzocar-
baporphyrins. Addition of excess pyrrolidine to solutions
of 1a in chloroform leads to the reversible formation of
the pyrrolidine adduct 22a (Scheme 8).31 This process is
an equilibrium and removal of the excess pyrrolidine
leads to the reformation of azuliporphyrin 1a. On addi-
tion of pyrrolidine, the solutions turn from a deep green
to a dark brown color that is typical of carbaporphyrin
systems. In the presence of increasing amounts of pyr-
rolidine, a Soret-like band emerges near 400 nm, and Q
type bands appear between 500 and 700 nm.31 The
pyrrolidine adduct has a true carbaporphyrin delocaliza-
tion pathway and this leads to a strong diatropic ring
current in the proton NMR spectra. In pyrrolidine-d8-
CDCl3, 22a gives a 1H singlet for the internal CH at -6.9
ppm, while the external meso-protons resonate downfield
at 9.7 and 9.9 ppm (Figure 4). The symmetry of the
system is evident from the simplicity of the spectrum,
confirming that the pyrrolidine attacks the carbon atom
furthest removed from the porphyrinoid macrocycle. It
should be noted that the observed adduct is the thermo-
dynamic product resulting from the equilibrium, and
nucleophilic attack may well also occur at other positions
on the cycloheptatriene ring. The alkene units of the
seven-membered ring give rise to a two 2H doublet of
doublets at 6.0 and 7.8 ppm. The latter resonance is
benzene-d6, these resonances were present at 8.9, 9.0, 8.7,
and 9.1 ppm, showing a decreased ring current, while
pyridine-d5 showed increased diatropicity with equivalent
resonances at 9.6, 9.8, 9.3, and 10.0 ppm, respectively.
Again, the internal CH resonance did not agree with this
trend and gave 1H resonances at 3.0, 3.5, and 3.4 ppm
in CDCl3, C6D6, and C5D5N, respectively. The results for
the external protons are consistent and suggest that the
thia- and selenaazuliporphyrins have comparable diat-
ropic character that is enhanced in pyridine but slightly
diminished in benzene. The chemical shift values for the
internal CH is most likely effected by subtle steric and
conformational factors, and these values provide a poorer
guide to the overall diatropicity of these systems.
Addition of TFA to solutions of 14b or 14c in chloro-
2+
form affords the corresponding dications 14H2 (Chart
5). These dications would be expected to take on greater
overall aromatic character due to favorable charge delo-
calization as was the case for 1a-c. The UV-vis spec-
trum of 14b in TFA-chloroform is more porphyrin-like,
showing a Soret band at 468 nm and a weaker absorption
J. Org. Chem, Vol. 69, No. 25, 2004 8857

Lash et al.
SCHEME 9
SCHEME 10
FIGURE 4. 400 MHz proton NMR spectrum of 1a in CDCl3
with one drop of pyrrolidine-d8. The resulting adduct shows
strongly diatropic character with the internal CH near -7
ppm. Insets A-C show details for the protons on the seven-
membered ring.
shifted downfield due to the proximity of the 21 and 31
protons to the 18π electron delocalization pathway. The
CH connected to the pyrrolidine nitrogen gave a 1H
triplet of triplets at 3.1 ppm. The porphyrin methyl
substituents resonated at 3.5 ppm as would be expected
for a species of this type with a fully aromatic porphy-
rinoid ring current.
Tetraarylazuliporphyrins 18 (Scheme 7) also form
adducts of this type with pyrrolidine, although trace
amounts of the 2° amine are sufficient to form this type
of species for this series. The formation of these adducts
may be more favored in the meso-tetrasubstituted por-
phyrinoids due to relief of steric congestion between the
seven-membered ring and the adjacent aryl substituents.
Thiaazuliporphyrin 14b also affords a pyrrolidine adduct
23a, but this requires a much larger excess of pyrrolidine
to drive the equilibrium (Scheme 9). Although the addi-
tion of one drop of pyrrolidine to 1 mg of 1a in CDCl3
was sufficient to completely form the adduct 22, 10 drops
were required to fully generate the corresponding core-
modified adduct 23a. The proton NMR spectrum was
similar to the one obtained from 1a, and the internal CH
was noted at -5.4 ppm for the thiaazuliporphyrin.
Selenaazuliporphyrin 14c also gave the corresponding
adduct 23b, but even larger proportions of pyrrolidine
were required in this case. Addition of 20 drops of
pyrrolidine-d8 to the NMR tube gave a spectrum where
the adduct predominated, and in this case the internal
CH resonated at -4.7 ppm. The larger sulfur and
selenium atoms may reduce the favorability of the
carbaporphyrinoid adduct by decreasing the planarity of
the macrocyclic core. However, the same type of chem-
istry can occur to a greater or lesser extent for all of the
azuliporphyrin systems.
The ability for azuliporphyrins to undergo nucleophilic
attack suggested that further chemistry may be possible
to form modified porphyrinoid structures. Under alkaline
conditions, azuliporphyrin 1a was reacted with tert-butyl
hydroperoxide in an attempt to generate the tropone
derivative 24 (Scheme 10).31 We had speculated that
nucleophilic attack by the tert-butyl hydroperoxide anion,
followed by elimination of tert-butyl alcohol, would afford
24.31 However, these reaction conditions gave benzocar-
baporphyrin products 4 and 9 instead. Using KOH as the
base in methanol-dichloromethane, 1a reacted with
t-BuOOH to give benzocarbaporphyrin 4 as the major
product in 31% yield. However, when the reaction was
performed using potassium tert-butoxide as the base, two
major carbaporphyrin products were isolated. Following
chromatography and recrystallization, 4 was isolated in
19% yield together with a 35% yield of the formyl
derivative 9a. A third minor fraction was noted that was
tentatively assigned as the isomeric aldehyde 9b. The
chemistry provides an alternative entry into benzocar-
baporphyrin systems, and this approach has been applied
to the synthesis of meso-tetraarylbenzocarbaporphyrins.46
8858 J. Org. Chem., Vol. 69, No. 25, 2004

Reactivity of Azuliporphyrins and Their Heteroanalogues
SCHEME 11
Detailed mechanisms to explain this chemistry involving
a nucleophilic addition, Cope rearrangement, elimination
process has been proposed elsewhere.31,46b A similar
process was presumably responsible for Breitmeier’s
results,18a as well as the formation of oxacarbaporphyrins
in the “3 + 1” chemistry using 2,5-furandicarbaldehyde
(Scheme 5). It was of additional interest to see whether
this chemistry also occurred for the core-modified azuli-
porphyrins 14b and 14c. Treatment of 14b with t-
BuOOH in the presence of KOH gave thiacarbaporphyrin
25a in 9.5% yield (Scheme 11). The carbaporphyrinoid
gave a porphyrin-like UV-vis spectrum in 1% Et3N-
CHCl3 with a Soret band at 434 nm. The proton NMR
spectrum for 21a in CDCl3 showed the inner CH as a
singlet at -5.90, the NH resonance as a broad peak at
-5.08 and the meso-protons as two 2H singlets near 10.1
ppm, values that confirm the presence of a powerful
diatropic ring current. When the reaction of 14b with
t-BuOOH was performed in the presence of t-BuOK, a
mixture of 25a and aldehyde 25b were isolated in
approximately 50% yield. These were generated in a 2:1
ratio, where the aldehyde predominated, but the two
products proved to be virtually impossible to separate.
The same differences in reaction selectivity clearly ap-
plies to the thiaazuliporphyrin system, again emphasiz-
ing the similarities between 1a and 14b. However, a
similar thiacarbaporphyrin has been synthesized by a
rational “3 + 1” route and the properties of this system
investigated in detail.43 For this reason, the chemistry
was not further pursued for thiaazuliporphyrin 14b.
Reactions of t-BuOOH with selenaazuliporphyrin 14c
gave similar results (Scheme 11). Using t-BuOK, 14c
gave selenacarbaporphyrin 26a in 10% yield. However,
using KOH as the base, 14c afforded two major prod-
ucts: 26a (16%) and the related aldehyde 26b (22%). In
this case the two major products could be separated by
flash chromatography and fully characterized.
FIGURE 5. (A) UV-vis spectrum of 23-selena-21-carbapor-
phyrin 26 in 1% Et3N-chloroform showing porphyrin-like
characteristics with a broadened Soret band at 436 nm. (B)
Partial 400 MHz proton NMR spectrum of 26 in CDCl3
showing the upfield and downfield regions. The internal CH
is present as a sharp singlet at -5 ppm, while the NH gives a
broad resonance near -4 ppm. The meso- and selenophene
protons give rise to three 2H singlets downfield below 10 ppm.
the presence of two downfield 2H singlets for the meso-
protons at 10.2 and 10.4 ppm. The selenophene protons
also gave a downfield 2H singlet at 10 ppm, while the
methyl substituents showed the indirect effect of the
diatropic ring current giving rise to a 6H singlet at 3.4
ppm. These results show that the diatropicity of thia- and
selenacarbaporphyrins is not significantly different from
benzocarbaporphyrins 4. Both 25 and 26 give NMR
spectra that show an apparent plane of symmetry,
although the presence of a single NH proton means that
this must be due the averaging of two equivalent tauto-
meric forms due to rapid NH exchange. Addition of trace
TFA gave the related monocation 26H+ (Scheme 12), and
the UV-vis spectrum for this species in 0.1% TFA-
CHCl3 gave a Soret band at 469 nm. At higher acid
concentrations, minor shifts were observed but these
spectra all appeared to correspond to 26H+. The proton
NMR spectrum of 26H+ in TFA-CDCl3 gave a 1H singlet
for the interior CH at -5.6 ppm and a 2H broad peak at
-4.3 ppm for the NH’s. The meso-protons shifted down-
Selenacarbaporphyrins have not previously been syn-
thesized and this new porphyrin analogue system was
further investigated. Due to the relative simplicity of the
spectra for 26a, the discussion will emphasize this
compound over the related asymmetrical aldehyde. How-
ever, apart from the obvious structural differences, the
two selenacarbaporphyrins gave similar spectroscopic
data. In 1% Et3N-CHCl3, 26a gave a porphyrin-like
spectrum with a relatively broad Soret band at λmax 436
nm and three weaker absorptions between 500 and 650
nm (Figure 5A). The proton NMR spectrum for 26a in
CDCl3 showed a singlet for the internal CH at -5.4 ppm
and a broad resonance for the NH at -4.9 ppm (Figure
5B). The strong diatropic ring current is confirmed by
J. Org. Chem, Vol. 69, No. 25, 2004 8859

Lash et al.
SCHEME 12
reactivity is also believed to be responsible for the oxi-
dative ring contraction of azuliporphyrins and hetero-
azuliporphyrins to give carbaporphyrins in the presence
of alkaline solutions of tert-butyl hydroperoxide. This
study provides efficient routes to the meso-unsubstituted
azuliporphyrins and makes available details of their
spectroscopic and chemical properties that will facilitate
future investigations in this area.
Experimental Section
1,3-Azulenedicarbaldehyde (6). Prepared by the Vils-
meier formylation of azulene (500 mg) using the procedure of
Hafner and Bernhard38 as burgundy needles (376 mg, 52%):
mp 190-191 °C (lit.33 mp 190 °C); 1H NMR (CDCl3) δ 7.96 (2H,
t, J ) 10 Hz), 8.15 (1H, t, J ) 9.8 Hz), 8.64 (1H, s), 9.89 (2H,
d, J ) 9.6 Hz), 10.35 (2H, s); 13C NMR (CDCl3) δ 126.1, 134.2,
140.9, 142.8, 144.5, 148.7, 187.3.
field to give two 2H resonances at 10.4 and 11.0 ppm,
while the selenophene protons gave a 2H singlet at 10.1
ppm and the methyl groups afforded a 6H resonance at
3.6 ppm. Taken together, these data indicate that the
ring current is slightly larger for the protonated struc-
ture. Addition of TFA-d to a solution of 26a in CDCl3
showed the immediate disappearance of the internal CH
and NH resonances. This indicates that a C-protonated
2,5-Selenophenedicarbaldehyde (13c). A mixture of
selenophene (2.50 g), TMEDA (2.712 g) and hexanes (6 mL)
was placed in a three neck round-bottom flask equipped with
a thermometer, a condenser, and a rubber septum. The vessel
was flushed with nitrogen for ca. 7 min, and the mixture cooled
to -5 °C with the aid of a salt-ice bath. A solution of tert-
butyllithium in pentane (1.5 M, 26 mL) was slowly added via
a syringe to the stirred mixture while maintaining the tem-
perature <5 °C. After the addition had been completed, the
solution was allowed to warm to room temperature and then
refluxed for 30 min. Freshly distilled THF (23 mL) was added,
and the solution cooled to -40 °C. DMF (5.60 g) was added
over a period of 10 min. After the addition had been completed,
the solution was allowed to warm to room temperature and
was stirred for a further 30 min. The solution was poured into
a mixture of concentrated hydrochloric acid (31 mL) in water
(325 mL) at -5 °C, and the pH was adjusted to a value of 6
with saturated sodium bicarbonate solution. The solution was
extracted with ether (4 × 250 mL), and the combined ether
extracts were dried over sodium sulfate. The solvent was
evaporated and the residue recrystallized from ethanol. The
crystals were dried in vacuo overnight to give the dialdehyde
(2.18 g, 61%) as pale brown crystals: mp 85 °C (lit.48 mp 83
°C); 1H NMR (CDCl3) δ 8.11 (2H, s), 9.89 (2H, s); 13C NMR
(CDCl3) δ 138.4, 156.3, 185.0.
Benzyl 5-(1-Azulenylmethyl)-4-ethyl-3-methylpyrrole-
2-carboxylate (10a) and 1,3-Bis(5-benzyloxycarbonyl-3-
ethyl-4-methyl-2-pyrrolylmethyl)azulene (12). Azulene (85
mg) and benzyl 5-acetoxymethyl-4-ethyl-3-methylpyrrole-2-
carboxylate49 (427 mg) were dissolved in 2-propanol (10 mL)
and acetic acid (1 mL). The mixture was flushed with nitrogen
and stirred under reflux overnight. The solution was allowed
to cool to room temperature and cooled in the freezer for 1 h.
The precipitate was filtered and washed with ethanol to give
the tripyrrane analogue (195 mg, 46%) as a blue powder. The
filtrate was evaporated to dryness on a rotary evaporator and
the residue chromatographed on silica eluting initially with
50% hexanes-dichloromethane and then gradually increasing
the proportion of dichloromethane to 100%. Initially a small
blue fraction containing azulene was collected, followed by a
blue band corresponding to the monopyrrolic product 12, and
finally the tripyrrane analogue 10a eluted as a deep blue
fraction. Compound 12 was recrystallized from ethanol to give
dark blue crystals (9 mg, 3.5%), while 10a recrystallized from
ethanol to afford blue crystals (115 mg, overall yield 73%). In
some experiments where the reaction temperature was barely
sufficient to achieve reflux, a higher proportion of byproduct
12 was observed. When azulene (85 mg) was reacted with 1
equiv of acetoxymethylpyrrole 11a (210 mg) under the same
2+
dication 26aH2 is present in equilibrium with the
monocation 26aH+ (Scheme 12). Similar C-protonated
cations have been observed for carbaporphyrins17 and
related systems.20,47 Over a period of 1 week at room
temperature, some loss of signal intensity for the peaks
at 10.4 and 11.0 ppm was noted indicating that slow
exchange was also occurring at the meso-positions. This
may be due to low concentrations of meso-C-protonated
species similar to those previously proposed for carba-
porphyrins 4.17
Conclusions
Azuliporphyrins are easily synthesized by reacting 1,3-
azulenedicarbaldehyde with tripyrranes under conven-
tional “3 + 1” conditions. Alternatively, azulene ana-
logues of the tripyrranes can be constructed by reacting
acetoxymethylpyrroles with azulene under mildly acidic
conditions, and following deprotection of the terminal
ester groups, reaction with a pyrrole dialdehyde gives the
azuliporphyrin system. This alternative “3 + 1” approach
has the advantage of making related core-modified azu-
liporphyrins easily accessible. Hence, reaction of the
azulitripyrrane with thiophene and selenophene dialde-
hydes affords the related thia- and selenaazuliporphyrins
in good yields. Although 2,5-furandicarbaldehyde failed
to give an oxaazuliporphyrin, a series of oxacarbapor-
phyrins were generated instead. Azuliporphyrins and
their core-modified analogues show intermediary diatro-
pic character falling midway between the nonaromatic
benziporphyrin system and the highly diatropic carba-
porphyrins. The intermediary porphyrinoid aromaticity
derives from dipolar resonance contributors that have a
carbaporphyrinoid core and a peripheral fused tropylium
cation. Protonation greatly enhances the diatropicity
because this type of canonical form now aids in charge
delocalization. Azuliporphyrins, thiaazuliporphyrins, and
selenaazuliporphyrins all form carbaporphyrin adducts
in the presence of excess pyrrolidine due to reversible
nucleophilic attack onto the cycloheptatriene ring. This
(48) Paulmier, C.; Pastour, P. Bull. Soc. Chim. Fr. 1966, 4021.
(49) Johnson, A. W.; Kay, I. T.; Markham, E.; Price, R.; Shaw, K.
B. J. Chem. Soc. 1959, 3416.
(47) Lash, T. D.; Richter, D. T. J. Am. Chem. Soc. 1998, 120, 9965.
8860 J. Org. Chem., Vol. 69, No. 25, 2004

Reactivity of Azuliporphyrins and Their Heteroanalogues
conditions, 12 was isolated as the major reaction product and
afforded dark blue crystals (125 mg, 49%) after recrystalliza-
tion from ethanol.
J ) 9.6 Hz), 8.49 (2H, s), 9.46 (2H, s), 9.64 (2H, d, J ) 9.8
Hz); 1H NMR (pyrrolidine-d8-CDCl3): δ -6.87 (1H, s), 1.76-
1.83 (12H, 2 overlapping triplets), 3.06 (1H, tt, J ) 2.8, 10
Hz), 3.53 (6H, s), 3.88 (4H, q, J ) 7.6 Hz), 3.98 (4H, q, J ) 7.6
Hz), 6.00 (2H, dd, J ) 5.2, 9.2 Hz), 7.82 (2H, dd, J ) 1.6, 9.0
Hz), 9.67 (2H, s), 9.88 (2H, s); 13C NMR (TFA-CDCl3) δ 11.5,
16.1, 16.9, 19.6, 95.2, 110.2, 124.9, 128.1, 140.3, 142.0, 142.1,
142.2, 142.4, 144.5, 144.8, 146.2, 147.5, 154.1; HR MS (FAB)
calcd for C36H37N3 + H m/z 512.3066, found 512.3072. Anal.
Calcd for C36H37N3‚H2O: C, 81.62; H, 7.42; N, 7.93. Found:
C, 81.23; H, 7.36; N, 7.86.
8,17-Diethyl-7,18-dimethyl-12,13-diphenylazuliporphy-
rin (1b). Tripyrrane 5b17b (303 mg) was reacted with 1,3-
azulenedicarbaldehyde (103 mg) under the foregoing condi-
tions. The crude product was chromatographed on Grade III
alumina, eluting with 5% methanol-chloroform, and recrys-
tallized from chloroform-hexanes to afford the porphyrin
analogue (260 mg, 77%) as dark green crystals: mp >300 °C;
UV-vis (5% Et3N-CHCl3) λmax (log ꢀ) 368 (4.78), 403 (4.70),
448 (4.67), 476 (4.78), 640 (3.69), 670 nm (3.70); UV-vis (5%
TFA-CHCl3) λmax (log ꢀ) 368 (4.64), 466 (4.82), 646 nm (3.93);
1H NMR (2 drops TFA-CDCl3) δ -2.96 (1H, s), -1.5 (1H, br
s), -0.14 (2H, s), 1.59 (6H, t, J ) 7.6 Hz), 3.49 (6H, s), 3.72
(4H, q, J ) 7.7 Hz), 7.69-7.74 (6H, m), 7.81-7.85 (4H, m),
8.54 (1H, t, J ) 9.6 Hz), 8.66 (2H, t, J ) 9.6 Hz), 9.62 (2H, s),
10.05 (2H, d, J ) 9.6 Hz), 10.46 (2H, s); 1H NMR (pyrrolidine-
d8-CDCl3) δ -6.82 (1H, s), 1.73 (6H, t, J ) 7.6 Hz), 3.11 (1H,
t, J ) 5.2 Hz), 3.57 (6H, s), 3.88 (4H, q, J ) 7.6 Hz), 6.05 (2H,
dd, J ) 5.2, 9.2 Hz), 7.57 (2H, t, J ) 7.6 Hz), 7.65 (4H, t, J )
7.4 Hz), 7.86 (2H, d, J ) 10 Hz), 7.94 (4H, d, J ) 7.6 Hz), 9.80
(2H, s), 9.97 (2H, s); 13C NMR (TFA-CDCl3) δ 11.6, 15.9, 19.6,
98.4, 110.0, 124.2, 128.6, 129.4, 129.7, 131.9, 132.0, 132.2,
140.5, 142.0, 142.3, 142.6, 142.9, 143.3, 146.4, 147.1, 154.4;
HRMS (FAB) calcd for C44H37N3 + H m/z 608.3066, found
608.3068. Anal. Calcd for C44H37N3‚1/4CHCl3: C, 83.35; H, 5.88;
N, 6.59. Found: C, 83.25; H, 5.30; N, 6.64.
12: mp 116.5 °C; 1H NMR (CDCl3) δ 1.10 (3H, t, J ) 7.6
Hz), 2.31 (3H, s), 2.52 (2H, q, J ) 7.6 Hz), 4.37 (2H, s), 5.20
(2H, s), 7.09-7.18 (2H, 2 overlapping triplets), 7.28-7.33 (5H,
m), 7.34 (1H, d, J ) 4 Hz), 7.59 (1H, t, J ) 10 Hz), 7.70 (1H,
d, J ) 4 Hz), 8.2 (1H, br s), 8.22 (1H, d, J ) 9.2 Hz), 8.31 (1H,
d, J ) 9.2 Hz); 13C NMR (CDCl3) δ 10.7, 15.6, 17.5, 24.6, 65.4,
117.0, 117.3, 122.4, 123.0, 123.8, 125.5, 127.5, 128.0, 128.1,
128.6, 132.8, 133.5, 136.3, 137.0, 137.1, 137.9 (2), 141.3, 161.5.
Anal. Calcd for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found:
C, 81.63; H, 6.52; N, 3.78.
1
10a: mp 141-143 °C; H NMR (CDCl3) δ 1.05 (6H, t, J )
7.6 Hz), 2.30 (6H, s), 2.47 (4H, q, J ) 7.5 Hz), 4.31 (4H, s),
5.20 (4H, s), 7.08 (2H, t, J ) 9.8 Hz), 7.27-7.33 (10H, m), 7.47
(1H, s), 7.56 (1H, t, J ) 9.8 Hz), 8.17 (2H, d, J ) 10 Hz), 8.20
(2H, br s); 13C NMR (CDCl3) δ 10.8, 15.6, 17.5, 24.5, 65.5, 117.1,
122.5, 123.9, 124.5, 127.6, 128.1 (2), 128.6, 132.7, 133.7, 136.9,
137.1, 138.5, 138.7, 161.5; HRMS (EI) calcd for C42H42N2O4
m/z 638.3144, found 638.3143. Anal. Calcd for C42H42N2O4: C,
78.97; H, 6.63; N, 4.38. Found: C, 79.02; H, 6.51; N, 4.47.
1,3-Bis(5-tert-butoxycarbonyl-3-ethyl-4-methyl-2-pyr-
rolylmethyl)azulene (10b). Azulene (438 mg) and tert-butyl
5-acetoxymethyl-4-ethyl-3-methylpyrrole-2-carboxylate50 (2.14
g) were dissolved in 2-propanol (50 mL) and acetic acid (10
mL). The mixture was purged with nitrogen and refluxed
overnight. The mixture was allowed to cool to room temper-
ature, and the solvent was removed under reduced pressure.
The residue was chromatographed on a silica column eluting
with 60% dichloromethane-hexanes. The major blue band was
collected and the solvent removed under reduced pressure. The
residue was recrystallized from toluene, and upon suction
filtration the product (1.027 g, 59%) was obtained as a baby
1
blue powder: mp 150 °C dec; H NMR (CDCl3) δ 1.07 (6H, t,
J ) 7.4 Hz), 1.47 (18H, s), 2.26 (6H, s), 2.48 (4H, q, J ) 7.4
Hz), 4.31 (4H, br s), 7.08 (1H, t, J ) 9.8 Hz), 7.49 (1H, s), 7.56
(2H, t, J ) 9.8 Hz), 8.11 (2H, br s), 8.18 (2H, d, J ) 10 Hz);
13C NMR (CDCl3) δ 10.7, 15.7, 17.6, 24.3, 28.7, 80.2, 118.7,
121.4, 124.7, 126.0, 131.6, 133.7, 137.0, 138.4, 138.7, 138.9,
161.5; HRMS (EI) calcd for C36H46N2O4 m/z 570.3458, found
570.3458. Anal. Calcd for C36H46N2O4: C, 75.76; H, 8.12; N,
4.91. Found: C, 75.30; H, 8.16; N, 4.60.
12,13-Butano-8,17-diethyl-7,18-dimethylazuliporphy-
rin (1c). Tripyrrane 5c35 (100 mg) was reacted with 1,3-
azulenedicarbaldehyde (40.6 mg) under the conditions de-
scribed above. The product was purified by chromatography
on Grade 3 basic alumina, eluting with chloroform. A deep
green fraction was collected, evaporated under reduced pres-
sure, and then recrystallized from chloroform-hexanes to give
the azuliporphyrin (47 mg, 42%) as a dark blue powder: mp
>300 °C; UV-vis (1% Et3N-CHCl3) λmax (log ꢀ) 354 (4.74), 396
(4.66), 444 (4.68), 472 (4.77), 614 (4.14), 662 nm (4.09); UV-
vis (1% TFA-CHCl3) λmax (log ꢀ) 368 (4.87), 464 (4.99), 642
8,12,13,17-Tetraethyl-7,18-dimethylazuliporphyrin (1a).
Tripyrranedicarboxylic acid 5a35,51 (100 mg) was stirred in TFA
(1 mL) under nitrogen for 10 min. The solution was diluted
with dichloromethane (19 mL), 1,3-azulenedicarbaldehyde (41
mg) was added, and the resulting mixture was stirred over-
night in the dark. Following neutralization by the dropwise
addition of triethylamine, DDQ (51 mg) was added, and the
resulting mixture was stirred for 1 h. The solution was washed
with water and the organic phase evaporated under reduced
pressure. Chromatographic separation of the residue was
carried out on Grade III alumina, eluting with 5% methanol-
chloroform. A deep green fraction was collected and evaporated
under reduced pressure, and the residue recrystallized from
chloroform-hexanes to give the azuliporphyrin (143 mg, 63%)
as dark green crystals: mp >300 °C; UV-vis (1% Et3N-
CH2Cl2) λmax (log ꢀ) 354 (4.78), 396 (4.69), 444 (4.70), 472 (4.81),
622 nm (4.16); UV-vis (0.5% TFA-CH2Cl2) λmax (log ꢀ) 364
(4.95), 460 (5.08), 592 (3.85), 638 (4.46), 678 (4.17), 734 nm
1
nm (4.36); H NMR (CDCl3): δ 1.53 (6H, t, J ) 7.6 Hz), 1.84
(1H, br s), 2.25-2.35 (4H, m), 2.96 (6H, s), 3.31 (4H, q, J )
7.6 Hz), 3.40-3.50 (4H, m), 7.61 (2H, t, J ) 10 Hz), 7.71 (1H,
t, J ) 10 Hz), 7.92 (2H, s), 8.87 (2H, s), 9.23 (2H, d, J ) 10
1
Hz); H NMR (C6D6) δ 1.56 (6H, t, J ) 7.6 Hz), 1.82 (4H, m),
2.86 (6H, s), 3.04 (4H, m), 3.27 (4H, q, J ) 7.6 Hz), 6.84 (1H,
t, J ) 10 Hz), 6.97 (2H, obscured by solvent), 7.93 (2H, s), 8.76
1
(2H, d, J ) 10 Hz), 8.85 (2H, s); H NMR (pyridine-d5, 50 °C)
δ 1.66 (6H, t, J ) 7.8 Hz), 2.06-2.12 (4H, m), 3.07 (6H, s),
3.34-3.38 (4H, m), 3.44 (4H, q, J ) 7.6 Hz), 3.86 (1H, s), 7.69
(2H, t, J ) 9.4 Hz), 7.78 (1H, t, obscured by solvent), 8.30 (2H,
s), 9.45 (2H, s), 9.64 (2H, d, J ) 10 Hz); 1H NMR (TFA-CDCl3)
δ -2.55 (1H, s), -1.5 (1H, v br s), 0.4 (2H, br s), 1.65 (6H, t,
J ) 7.6 Hz), 2.40-2.48 (4H, m), 3.44 (6H, s), 3.79 (4H, q, J )
7.6 Hz), 3.8-3.86 (4H, m), 8.47 (1H, t, J ) 10 Hz), 8.57 (2H,
t, J ) 9.6 Hz), 9.33 (2H, s), 9.95 (2H, d, J ) 9.6 Hz), 10.32
(2H, s); 13C NMR (TFA-CDCl3) δ 11.5, 15.9, 19.5, 22.5, 23.0,
94.8, 110.9, 124.4, 128.1, 140.4, 141.8, 142.3, 142.4, 142.5,
142.6, 144.6, 146.4, 147.8, 154.0; HR MS (ESI) calcd for
C36H35N3 + H m/z 510.2909, found 510.2909.
1
(3.82); H NMR (TFA-CDCl3) δ -2.98 (1H, s), -2.13 (1H, br
s), -0.43 (2H, s), 1.67 (6H, t, J ) 7.6 Hz), 1.78 (6H, t, J ) 7.8
Hz), 3.50 (6H, s), 3.89 (8H, 2 overlapping quartets), 8.57 (1H,
t, J ) 9.6 Hz), 8.67 (2H, t, J ) 9.6 Hz), 9.60 (2H, s), 10.06 (2H,
d, J ) 4.8 Hz), 10.45 (2H, s); 1H NMR (pyridine-d5) δ 1.65 (12H,
t, J ) 7.4 Hz), 3.08 (6H, s), 3.43-3.53 (8H, 2 overlapping
quartets), 4.06 (1H, br s), 7.70 (2H, t, J ) 9.4 Hz), 7.79 (1H, t,
7,12,13,18-Tetraethyl-8,17-dimethylazuliporphyrin
(14a). Azulitripyrrane analogue 10a (100 mg) was stirred in
TFA (2 mL) under nitrogen for 10 min. The reaction mixture
was diluted with dichloromethane (100 mL), 3,4-diethylpyr-
role-2,5-dicarbaldehyde35,52 (31 mg) was added, and the reac-
(50) Clezy, P. S.; Crowley, R. J.; Hai, T. T. Aust. J. Chem. 1982, 35,
411.
(51) Sessler, J. L.; Johnson, M. R.; Lynch, V. J. Org. Chem. 1987,
52, 4394.
J. Org. Chem, Vol. 69, No. 25, 2004 8861

Lash et al.
tion mixture was stirred overnight in the dark. The solution
was neutralized by the dropwise addition of triethylamine,
DDQ (42 mg) was added, and the resulting mixture stirred
for 1 h. The dark green solution was washed with water and
the organic phase evaporated under reduced pressure. The
residue was chromatographed on Grade III alumina, eluting
with 2% methanol-chloroform. A deep green fraction was
collected and evaporated under reduced pressure and the
residue recrystallized from chloroform-hexanes. Suction fil-
tration afforded the title azuliporphyrin (32 mg, 36%) as dark
green crystals: mp >300 °C; UV-vis (1% Et3N-CHCl3) λmax
(log ꢀ) 355 (4.74), 397 (4.67), 444 (4.67), 472 (4.76), 620 nm
(4.13); UV-vis (2% TFA-CHCl3) λmax (log ꢀ) 366 (4.89), 463
(4.99), 643 nm (4.36); UV-vis (5% pyrrolidine-CHCl3) λmax (log
shaken with 0.1% aqueous ferric chloride solution (150 mL)
for 10 min. The organic layer was separated and washed with
water, 5% sodium bicarbonate solution, and water. The organic
phase was dried over sodium sulfate and evaporated under
reduced pressure and the residue chromatographed and
recrystallized as before. The thiaazuliporphyrin (40.4 mg, 45%)
was isolated as dark green crystals: mp >300 °C.
7,18-Diethyl-8,17-dimethyl-23-selenaazuliporphyrin
(14c). Azulitripyrrane 10b (100 mg) was reacted with 2,5-
selenophenedicarbaldehyde (35 mg) by method B, as described
above. The crude product was purified by chromatography on
Grade 3 neutral alumina, eluting with chloroform. A dark
green band was collected and evaporated to dryness under
reduced pressure and the residue recrystallized from chloro-
form-hexanes to give the selenaazuliporphyrin (24.2 mg, 27%)
as a deep green powder: mp >300 °C; UV-vis (1% Et3N-
CHCl3) λmax (log ꢀ) 363 (4.73), 399 (4.66), 449 (4.62), 476 (4.67),
627 (4.14), 666 nm (4.15); UV-vis (5% TFA-CHCl3) λmax (log
ꢀ) 368 (4.57), 382 (4.55), 494 (4.97), 625 (3.90), 682 nm (4.07);
UV-vis (25% pyrrolidine-CHCl3) λmax (log ꢀ) 446 (4.95), 474
1
ꢀ) 407 (4.98), 523 (4.24), 560 (4.08), 629 nm (3.50); H NMR
(TFA-CDCl3) δ -2.87 (1H, s), -1.98 (1H, br s), -0.23 (2H, s),
1.73 (12H, 2 overlapping triplets), 3.37 (6H, s), 3.88 (4H, q),
3.95 (4H, q), 8.54 (1H, t, J ) 9.2 Hz), 8.64 (2H, t, J ) 9.6 Hz),
9.54 (2H, s), 10.02 (2H, d, J ) 9.6 Hz), 10.40 (2H, s); 13C NMR
(TFA-CDCl3) δ 11.3, 16.4, 17.0, 19.7, 20.06, 95.3, 109.6, 123.7,
128.1, 135.9, 140.5, 140.9, 142.6, 144.2, 145.2, 146.5, 148.0,
148.9, 154.0; HR MS (ESI) calcd for C36H35N3 + H m/z
512.3066, found 512.3067. Anal. Calcd for C36H37N3‚1/4CHCl3:
C, 80.40; H, 6.93; N, 7.76. Found: C, 80.50; H, 6.53; N, 7.60.
1
(4.83), 600 nm (4.20); H NMR (CDCl3) δ 1.61 (6H, t, J ) 7.6
Hz), 2.86 (6H, s), 3.04 (1H, s), 3.43 (4H, q, J ) 7.6 Hz), 7.84
(2H, t, J ) 9.2 Hz), 7.93 (1H, t, J ) 9.8 Hz), 8.93 (2H, s), 9.18
(2H, s), 9.21 (2H, s), 9.51 (2H, d, J ) 9.2 Hz); 1H NMR (C6D6)
δ 1.53 (6H, t, J ) 7.8 Hz), 2.62 (6H, s), 3.30 (4H, q, J ) 7.6
Hz), 3.53 (1H, s), 6.87-7.1 (3H, obscured by solvent), 8.69 (2H,
s), 8.93 (2H, d, J ) 9.2 Hz), 8.99 (2H, s), 9.07 (2H, s); 1H NMR
(pyridine-d5) δ 1.57 (6H, t, J ) 7.4 Hz), 2.86 (6H, s), 3.40 (1H,
s), 3.48 (4H, q, J ) 7.6 Hz), 7.85 (2H, t, J ) 9.4 Hz), 7.94 (1H,
t, J ) 9.2 Hz), 9.27 (2H, s), 9.56 (2H, s), 9.78 (2H, s), 9.98 (2H,
d, J ) 10 Hz); 1H NMR (20 drops pyrrolidine-d8-CDCl3) δ
-4.75 (1H, s), 1.55 (6H, t, partially obscured by water peak),
2.84 (1H, t, J ) 5.2 Hz), 3.03 (6H, s), 3.48-3.56 (4H, m), 5.68
(2H, dd, J ) 5.2, 9.2 Hz), 7.72 (2H, d, J ) 10 Hz), 9.64 (2H, s),
9.67 (2H, s), 10.10 (2H, s);1H NMR (TFA-CDCl3) δ -2.61 (1H,
s), -1.62 (2H, br s), 1.78 (6H, t, J ) 7.4 Hz), 3.48 (6H, s), 4.07
(4H, q, J ) 7.6 Hz), 8.81 (1H, t, J ) 9.4 Hz), 8.93 (2H, t, J )
9.8 Hz), 9.94 (2H, s), 10.38 (2H, d, J ) 8.8 Hz), 10.73 (2H, s),
10.83 (2H, s); 13C NMR (TFA-CDCl3) δ 11.2, 16.4, 20.2, 112.7,
115.0, 120.7, 129.4, 129.5, 138.1, 140.0, 140.1, 141.6, 141.7,
144.7, 148.4, 151.3, 151.4, 151.6, 156.3, 158.5; HRMS (ESI)
calcd for C32H28N2Se + H m/z 521.1496, found 521.1517. Anal.
Calcd for C32H28N2Se‚1/20CHCl3: C, 73.25; H, 5.38; N, 5.33.
Found: C, 73.20; H, 5.23; N, 5.29.
7,18-Diethyl-8,17-dimethyl-23-thiaazuliporphyrin (14b).
Method A. Azulitripyrrane analogue 10b (100 mg) was stirred
in TFA (1 mL) under nitrogen for 10 min. The reaction mixture
was diluted with dichloromethane (100 mL), 2,5-thiophenedi-
carbaldehyde (41 mg) was added, and the reaction mixture was
stirred overnight in the dark. The solution was neutralized
by the dropwise addition of triethylamine, DDQ (50 mg) was
added, and the resulting mixture was stirred for 1 h. The dark
green solution was washed with water, and the organic phase
evaporated under reduced pressure. The residue was chro-
matographed on Grade III alumina, eluting with chloroform.
A deep green fraction was collected and evaporated under
reduced pressure. Recrystallization from chloroform-hexanes
gave the porphyrinoid (29.2 mg, 33%) as dark green crystals:
mp >300 °C; UV-vis (5% Et3N-CH2Cl2) λmax (log ꢀ) 372 (4.74),
384 (4.72), 448 (4.59), 477 (4.66), 632 (4.07), 672 nm (4.10);
UV-vis (5% TFA-CH2Cl2) λmax (log ꢀ) 385 (4.54), 468 (4.92),
601 (3.78), 661 nm (4.14); 1H NMR (CDCl3) δ 1.61 (6H, t, J )
7.8 Hz), 2.76 (1H, br s), 2.88 (6H, s), 3.45 (4H, q, J ) 7.7 Hz),
7.80-7.92 (3H, m), 8.82 (2H, s), 9.05 (2H, s), 9.24 (2H, s), 9.52
(2H, d, J ) 9.2 Hz); 1H NMR (C6D6) δ 1.56 (6H, t, J ) 7.4 Hz),
2.66 (6H, s), 3.34 (4H, q, J ) 8 Hz), 6.89 (1H, t), 6.97 (2H,
obscured by solvent), 8.46 (2H, s), 8.83 (2H, s), 8.94 (2H, d,
Synthesis of Oxabenzocarbaporphyrins 15a-c. Azu-
litripyrrane 10b (100 mg) was stirred in TFA (1 mL) under
nitrogen for 10 min. The reaction mixture was diluted with
dichloromethane (19 mL), and 2,5-furandicarbaldehyde (40
mg) was added immediately. The reaction mixture was purged
with nitrogen and stirred overnight in the dark. The solution
was neutralized with triethylamine, DDQ (50 mg) was added,
and the resulting mixture was stirred for 1 h. The solution
was washed with 2 M aqueous hydrochloric acid. The organic
phase was separated and the solvent removed under reduced
pressure. The residue was chromatographed on a silica column,
eluting first with chloroform and then gradually increasing
the polarity to 5% methanol-chloroform. A deep green fraction
was collected and evaporated under reduced pressure. The
residue was recolumned using flash chromatography eluting
with 5% methanol-chloroform. Three separate green fractions
corresponding to oxacarbaporphyrins 15a-c were collected;
the order of elution was 15a, 15c, then 15b. Recrystallization
from chloroform-hexanes gave the oxacarbaporphyrins as
dark green crystals.
1
J ) 9.6 Hz), 9.13 (2H, s); H NMR (pyridine-d5): δ 1.59 (6H,
t, J ) 7.2 Hz), 2.89 (6H, s), 3.20 (1H, s), 3.52 (4H, q, J ) 7.7
Hz), 7.78-7.93 (3H, m), 9.13 (2H, s), 9.44 (2H, s), 9.82 (2H, s),
1
9.98 (2H, d, J ) 10 Hz); H NMR (10 drops pyrrolidine-d8-
CDCl3) δ -5.42 (1H, s), 1.62 (6H, t, J ) 7.6 Hz), 2.96 (1H, t),
3.24 (6H, s), 3.72 (4H, q, J ) 7.5 Hz), 5.87 (2H, dd, J ) 5.2,
9.2 Hz), 7.83 (2H, d, J ) 9.2 Hz), 9.67 (2H, s), 9.85 (2H, s),
10.18 (2H, s); 1H NMR (TFA-CDCl3) δ -3.44 (1H, s), -1.5
(2H, v br s), 1.79 (6H, t, J ) 7.8 Hz), 3.49 (6H, s), 4.05 (4H, q,
J ) 7.7 Hz), 8.78 (1H, t, J ) 9.6 Hz), 8.92 (2H, t, J ) 10 Hz),
9.99 (2H, s), 10.38 (2H, d, J ) 10 Hz), 10.60 (2H, s), 10.86
(2H, s); 13C NMR (TFA-CDCl3) δ 11.4, 16.6, 20.2, 111.7, 111.9,
130.4, 138.5, 139.8, 141.1, 141.9, 145.3, 148.4, 148.7, 150.1,
150.3, 157.2, 161.0; HRMS (FAB) calcd for C32H28N2S + H m/z
473.2051, found 473.2049. Anal. Calcd for C32H28N2S‚
2/5CHCl3: C, 74.78; H, 5.50; N, 5.38. Found: C, 74.78; H, 5.61;
N, 5.36.
Method B. Azulitripyrrane 10b (101.3 mg) was stirred in
TFA (2 mL) under nitrogen for 10 min. The reaction mixture
was diluted with dichloromethane (100 mL), 2,5-thiophenedi-
carbaldehyde (41 mg) was added, and the reaction mixture was
stirred overnight in the dark. The solution was vigorously
15a. HCl: 5.8 mg (7.5%); mp >300 °C; UV-vis (5% Et3N-
CHCl3) λmax (log ꢀ) 372 (4.61), 430 (4.79), 522 (4.11), 555 (3.83),
620 (3.76), 681 nm (3.34); UV-vis (2% TFA-CHCl3) λmax (log
ꢀ) 393 (4.80), 410 (4.72), 477 (4.40), 573 (4.00), 609 nm (4.07);
UV-vis (5% TFA-CHCl3) λmax (log ꢀ) 393 (4.81), 411 (4.77),
1
573 (3.97), 610 nm (4.07); H NMR (CDCl3) δ -6.72 (1H, s),
-2.72 (2H, br s), 1.77 (6H, t, J ) 7.6 Hz), 3.58 (6H, s), 4.09
(4H, q, J ) 7.6 Hz), 7.68-7.73 (2H, m), 8.63-8.67 (2H, m),
(52) Tardieux, C.; Bolze, F.; Gros, C. P.; Guilard, R. Synthesis 1998,
267.
8862 J. Org. Chem., Vol. 69, No. 25, 2004

Reactivity of Azuliporphyrins and Their Heteroanalogues
9.85 (2H, s), 10.15 (2H, s), 10.36 (2H, s); 13C NMR (CDCl3) δ
11.7, 17.3, 20.2, 94.8, 105.7, 121.7, 128.4, 134.0, 137.3, 138.9,
140.7, 142.0, 142.2, 152.7; HRMS (EI) calcd for C31H28N2O m/z
444.2201, found 444.2201.
15b. HCl: 4.7 mg (5.7%); mp >300 °C; UV-vis (5% Et3N-
CHCl3) λmax (log ꢀ) 432 (4.93), 523 (4.13), 557 (4.03), 621 (3.82),
683 nm (3.52); UV-vis (5% TFA-CHCl3) λmax (log ꢀ) 392 (4.65),
434 (4.97), 472 (4.61), 566 (4.02), 607 (4.21), 646 nm (3.36); 1H
NMR (CDCl3) δ -6.40 (1H, s), -1.64 (2H, br s), 1.75-1.81 (6H,
t, J ) 7.6 Hz), 3.53 (6H, s), 4.05 (4H, q, J ) 7.6 Hz), 8.20 (1H,
d, J ) 7.6 Hz), 8.79 (1H, d, J ) 8.0 Hz), 9.15 (1H, s), 9.79 (2H,
s), 10.09 (2H, AB q), 10.34 (1H, s), 10.40 (1H, s), 10.43 (1H, s);
HRMS (EI) calcd for C32H28N2O2 m/z 472.2150, found 472.2143.
15c. HCl: 1.4 mg (1.7%); mp >300 °C; UV-vis (5% Et3N-
CHCl3) λmax (rel int.) 371 (0.46), 431 (1.00), 525 (0.17), 558
(0.12), 620 (0.08), 681 nm (0.05); UV-vis (5% TFA-CHCl3)
λmax (rel int) 390 (0.61), 435 (1.00), 476 (0.46), 576 (0.13), 604
(0.15), 657 nm (0.04); 1H NMR (CDCl3) δ -6.39 (1H, s), -1.8,
-1.6 (2H, 2 overlapping broad singlets), 1.76 (6H, 2 overlap-
ping triplets), 3.56 (6H, s), 4.09 (2H, q, J ) 7 Hz), 4.17 (2H, q,
J ) 7 Hz), 7.90 (1H, t, J ) 7.6 Hz), 8.19 (1H, d, J ) 7.5 Hz),
8.95 (1H, d, J ) 7.5 Hz), 9.81 (2H, s), 10.12-10.16 (2H, AB q),
10.42 (1H, s), 10.87 (1H, s), 12.03 (1H, s); HRMS (EI) calcd
for C32H28N2O2 m/z 472.2151, found 472.2149.
(42.3 mg) was reacted with tert-butyl hydroperoxide (5 M in
hexane, 70 µL) for 2 h. The crude product was run through a
flash silica column, eluting with 30/70 hexanes/dichloromethane.
An orange band eluted, and this was evaporated under reduced
pressure and the residue recrystallized from chloroform-
hexanes to give selenabenzocarbaporphyrin 26a (4.2 mg,
10.2%) as black crystals: mp 282-284 °C dec; UV-vis (1%
Et3N-CHCl3) λmax (log ꢀ) 436 (4.93), 533 (4.11), 565 (3.94), 630
nm (3.77); UV-vis (0.1% TFA-CHCl3) λmax (log ꢀ) 314 (4.44),
379 (4.39), 469 (4.85), 511 (4.51), 637 nm (4.02); UV-vis (10%
TFA-CHCl3) λmax (log ꢀ) 308 (4.37), 332 (4.31), 445 (4.86), 633
nm (4.11); 1H NMR (CDCl3, 30 °C) δ -5.38 (1H, s), -4.86 (1H,
br s), 1.79 (6H, t, J ) 7.6 Hz), 3.38 (6H, s), 3.89 (4H, q, J ) 7.6
Hz), 7.75-7.78 (2H, m), 8.82-8.84 (2H, m), 9.96 (2H, s), 10.16
(2H, s), 10.43 (2H, s); 1H NMR (trace TFA-CDCl3) δ -5.57
(1H, s), -4.31 (2H, br s), 1.83 (6H, t, J ) 7.6 Hz), 3.61 (6H, s),
4.10 (4H, q, J ) 7.6 Hz), 7.72-7.75 (2H, m), 8.68-8.71 (2H,
m), 10.09 (2H, s), 10.42 (2H, s), 10.99 (2H, s); 13C NMR (CDCl3)
δ 11.3, 17.5, 19.9, 106.1, 111.2, 116.4, 120.6, 127.0, 133.5, 134.0,
135.9, 142.8, 143.8, 146.0; 13C NMR (trace TFA-CDCl3) δ 11.7,
17.1, 20.1, 105.5, 112.1, 113.7, 121.9, 129.1, 136.9, 137.3, 140.1,
140.9, 142.1, 142.6, 144.3, 151.8; HR MS (ESI) calcd for
C31H28N2Se + H 509.1496, found 509.1488.
Method B. Selenaazuliporphyrin 14c (43.1 mg) was reacted
with tert-butyl hydroperoxide (5 M in hexane, 70 µL) for 4 h
using method B (above). The crude product was run through
a flash silica column, eluting with 30/70 hexanes/dichloro-
methane. After the first orange band corresponding to 26a had
eluted, the polarity was increased to straight dichloromethane.
After some minor impurity bands had eluted, a second orange
band corresponding to formyl selenabenzocarbaporphyrin 26b
was collected. The two major fractions were evaporated and
recrystallized from chloroform-hexanes. The first band gave
selenabenzocarbaporphyrin 26a (6.7 mg, 16%) as dark purple
needles that gave spectroscopic properties identical to those
of the compound prepared by method A. The second major
fraction afforded the aldehyde 26b (9.6 mg, 22%) as shiny black
crystals: mp 281-282 °C dec; UV-vis (1% Et3N-CHCl3) λmax
(log ꢀ) 439 (5.04), 540 (4.10), 571 (4.10), 628 (3.81), 687 nm
(3.28); UV-vis (1% TFA-CHCl3) λmax (log ꢀ) 311 (4.46), 334
(4.42), 384 (4.37), 464 (5.00), 500 (4.65), 632 nm (4.09); 1H NMR
(CDCl3, 20 °C) δ -6.48 (1H, s), -6.34 (1H, br s), 1.69 (6H, br
m), 3.24 (3H, s), 3.26 (3H, s), 3.65-3.75 (4H, m), 8.14 (1H, dd,
J ) 1.2, 7.6 Hz), 8.97 (1H, br d), 9.60 (2H, br), 9.74 (2H, s),
10.08 (1H, s), 10.10 (1H, s), 10.42 (1H, s); 1H NMR (trace TFA-
CDCl3, 20 °C) δ -5.35 (1H, s), -4.81 (2H, br s), 1.89 (6H, t,
J ) 7.6 Hz), 3.70 (3H, s), 3.71 (3H, s), 4.18-4.27 (4H,
2 overlapping quartets), 8.46 (1H, d, J ) 7.6 Hz), 9.10 (1H, d,
J ) 7.2 Hz), 9.55 (1H, s), 10.27 (2H, s), 10.34 (1H, s), 10.73
(1H, s), 10.82 (1H, s), 11.19 (2H, s, resolves into 2 singlets at
30 °C); 13C NMR (trace TFA-CDCl3) δ 11.7 (2), 17.0, 20.1, 20.2,
106.7, 106.9, 110.4, 112.9, 113.0, 113.2, 114.2, 116.1, 118.9,
122.6, 122.7, 134.2, 135.8, 137.7, 137.9, 138.0, 138.2, 138.6,
140.5, 140.8, 142.5, 142.9, 143.1, 146.1, 146.3, 148.4, 151.6,
151.8, 196.9; HR MS (ESI) calcd for C32H28N2OSe + H
537.1445, found 537.1435.
Oxidative Ring Contraction of Thiazuliporphyrin 14b.
Method A. Potassium tert-butoxide (1.0 M) in tert-butyl
alcohol (100 mL) was added to a solution of thiaazuliporphyrin
(101 mg) in dichloromethane (100 mL), and the resulting
stirred mixture was purged with nitrogen for 10 min. A
solution of tert-butyl hydroperoxide in decane (5 M, 150 µL)
was added and the resulting solution stirred under nitrogen
in the dark at room temperature for 4 h. The solution was
washed with water (×2), dried over sodium sulfate, and
evaporated under reduced pressure. The residues were chro-
matographed on a flash silica column, eluting with dichlo-
romethane. The first major orange band was collected, the
solvent evaporated, and the residue recrystallized from chlo-
roform-hexanes to give thiabenzocarbaporphyrin 25a (9.3 mg,
9.5%) as a black powder: mp >300 °C; UV-vis (1% Et3N-
CHCl3) λmax (log ꢀ) 390 (4.54), 434 (4.84), 530 (4.11), 557 (sh,
3.88), 625 (3.72), 684 nm (3.11); UV-vis (0.02% TFA-CHCl3)
λmax (log ꢀ) 448 (4.76), 495 (4.37), 620 (3.93), 688 nm (3.41); 1H
NMR (CDCl3) δ -5.90 (1H, s), -5.08 (1H, br s), 1.79 (6H, t,
J ) 7.6 Hz), 3.37 (6H, s), 3.87 (4H, q, J ) 7.6 Hz), 7.76-7.79
(2H, m), 8.83-8.86 (2H, m), 9.72 (2H, s), 10.06 (2H, s), 10.11
(2H, s); 1H NMR (TFA-CDCl3) δ -6.87 (1H, s), -5.34 (2H, br
s), 1.84 (6H, br t), 3.67 (6H, s), 4.11 (4H, br q), 7.79-7.86 (2H,
m), 8.74-8.82 (2H, m), 10.29 (2H, s), 10.46 (2H, s), 10.96 (2H,
s); 13C NMR (CDCl3) δ 11.4, 17.6, 19.8, 104.9, 107.5, 116.1,
120.6, 127.1, 131.7, 134.4, 136.9, 140.5, 142.7, 143.9; 13C NMR
(TFA-CDCl3) δ 11.9, 17.2, 20.1, 105.2, 108.9, 114.0, 122.3,
129.7, 136.2, 138.1, 139.7, 141.3, 141.5, 141.9, 142.0, 143.8;
HRMS (EI) calcd for C31H28N2S m/z 460.1973, found 460.1970.
Method B. Potassium hydroxide (475 mg) in methanol (60
mL) was added to a solution of thiaazuliporphyrin (60.3 mg)
in dichloromethane (60 mL), and the resulting stirred mixture
was purged with nitrogen for 10 min. A solution of tert-butyl
hydroperoxide in decane (5 M, 90 µL) was added and the
resulting solution stirred under nitrogen in the dark at room
temperature for 2 h. The solution was washed with water (×2),
dried over sodium sulfate, and evaporated under reduced
pressure. The residues were chromatographed on a flash silica
column, eluting initially with dichloromethane and then 75%
chloroform-dichloromethane. The major orange band was
collected, the solvent evaporated, and the residue recrystallized
from chloroform-hexanes to give a purple powder (33.5 mg)
corresponding to a mixture of 25a and 25b. These derivatives
could not be separated using flash chromatography. Although
the ratio of the two major products varied, the ratio of 25b to
25a was usually approximately 2:1.
Oxidative Ring Contraction of Azuliporphyrin 1a.
Method A. Azuliporphyrin 1a (40.0 mg) was reacted with tert-
butyl hydroperoxide (5 M in hexane, 78 µL) in the presence of
potassium tert-butoxide under the conditions described for
method A (above) for 2 h. The crude product was run through
a flash silica column, eluting with 20/80 hexanes/dichloro-
methane. A major orange-brown band eluted, and this was
evaporated under reduced pressure and the residue recrystal-
lized from chloroform-hexanes to give benzocarbaporphyrin
417a,b (12 mg, 31%) as a fluffy brown solid, mp >300 °C. This
material was indistinguishable from the carbaporphyrin ob-
tained from tripyrrane 5a and diformylindene.17 A minor more
polar band corresponding to <5% of 9a was also collected.
Method B. Azuliporphyrin 1a (40.0 mg) was reacted with
tert-butyl hydroperoxide (5 M in hexane, 78 µL) in the presence
of potassium hydroxide for 4 h using method B (above). The
Oxidative Ring Contraction of Selenaazuliporphyrin
14c. Method A. Using method A (above), selenaazuliporphyrin
J. Org. Chem, Vol. 69, No. 25, 2004 8863

Lash et al.
crude product was run through a flash silica column, eluting
with 20/80 hexanes/dichloromethane. Two major orange-brown
bands were collected, together with a minor band of intermedi-
ary polarity. The first band was evaporated down and the
residue recrystallized from chloroform-methanol to give ben-
zocarbaporphyrin 417a,b (7.6 mg, 19%) as a brown solid, mp
>300 °C. The more polar band was also evaporated down and
recrystallized from chloroform-methanol to give the aldehyde
9a (14.6 mg, 35%) as purple crystals: mp >300 °C; UV-vis
(1% Et3N-CHCl3) λmax (log ꢀ) 375 (4.53), 433 (5.26), 489 (3.98),
519 (4.17), 557 (4.39), 605 (3.87), 668 nm (3.24); 1H NMR (400
MHz, CDCl3) δ -7.55 (1H, s), -4.77 (2H, br s), 1.76-1.82 (6H,
two overlapping triplets), 1.85 (6H, t, J ) 7.6 Hz), 3.40 (3H,
s), 3.43 (3H, s), 3.88-3.99 (8H, m), 7.99 (1H, d, J ) 8 Hz),
8.47 (1H, d, J ) 8 Hz), 8.85 (1H, s), 9.52 (2H, s), 9.58 (1H, s),
9.60 (1H, s), 10.29 (1H, s); 13C NMR (CDCl3) δ 11.4 (2), 17.5,
18.7, 19.6 (2), 20.1, 95.3, 95.4, 98.8, 110.6, 120.2, 120.6, 128.9,
130.8, 131.2, 132.9, 133.0, 134.5, 134.9, 135.9, 136.0, 137.7,
141.0, 144.6, 144.7, 146.1, 153.2, 153.3, 193.0; HR MS (EI)
calcd for C36H37N3O m/z 527.2936, found 527.2933. Anal. Calcd
for C36H37N3O‚1/8CHCl3: C, 79.96; H, 6.89; N, 7.74. Found: C,
80.23; H, 6.34; N, 7.80.
Acknowledgment. This material is based upon
work supported by the National Science Foundation
under Grant Nos. CHE-9732054 and CHE-0134472 and
the Petroleum Research Fund, administered by the
American Chemical Society.
1
Supporting Information Available: UV-vis, H NMR,
13C NMR, and mass spectra for selected compounds are
provided. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO0402531
8864 J. Org. Chem., Vol. 69, No. 25, 2004