Synthesis of sapphyrins, heterosapphyrins, and carbasapphyrins by a "4 + 1" approach

Article abstract of DOI:10.1021/jo040239o

Sapphyrins are an important group of expanded porphyrins that show valuable anion binding characteristics. In this study, a "4 + 1" route to sapphyrin systems has been developed. Reaction of dialdehydes with a known tetrapyrrole intermediate 11b incorpora

Full text of DOI:10.1021/jo040239o

Synthesis of Sapphyrins, Heterosapphyrins, and Carbasapphyrins
by a “4 + 1” Approach†
Daniel T. Richter and Timothy D. Lash*
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160
tdlash@ilstu.edu
Received July 19, 2004
Sapphyrins are an important group of expanded porphyrins that show valuable anion binding
characteristics. In this study, a “4 + 1” route to sapphyrin systems has been developed. Reaction
of dialdehydes with a known tetrapyrrole intermediate 11b incorporating a bipyrrolic subunit
afforded a wide range of sapphyrin-type products. The best conditions for these reactions involved
carrying out the condensation of the dialdehydes with the tetrapyrrole in TFA-dichloromethane,
followed by oxidation with dilute aqueous solutions of ferric chloride. A pyrrole dialdehyde reacted
under these conditions to give sapphyrin in 50% yield, while furan and thiophene dialdehydes
afforded the corresponding oxa- and thiasapphyrins in 66-90% yield. Pyrrole dialdehydes with
fused phenanthrene or acenaphthylene rings also reacted with 11b to give the related phenanthro-
and acenaphthosapphyrins in excellent yields. As was the case for acenaphthoporphyrins, the
acenaphthosapphyrin gave longer wavelength absorptions than the corresponding phenanthrene
fused structure, although the differences were not as marked as those seen in the porphyrin series.
Reaction of 11b with 1,3-diformylindene gave a benzocarbasapphyrin in 38% yield, while a triformyl
cyclopentadiene reacted with the tetrapyrrole to give a carbasapphyrin aldehyde in 7-12% yield.
The free base carbasapphyrins were unstable but the monoprotonated hydrochloride salts could
easily be isolated and characterized. Carbasapphyrins retain a strong diatropic ring current due
to the presence of 22π electron delocalization pathways. In the presence of trifluoroacetic acid,
C-protonated dications are generated. Condensation of 1,3-azulenedicarbaldehyde with 11b gave
an azulisapphyrin dihydrochloride salt in 35% yield, and this also showed a strong diatropic ring
current. Addition of base gave the unstable free base form, while pyrrolidine formed an unstable
adduct that showed an intense Soret band at 480 nm. These results demonstrate that many of the
themes observed for modified porphyrins and carbaporphyrins also apply to the sapphyrin series,
although in some cases reduced stability hampers these investigations.
CHART 1
Introduction
Expanded porphyrins1-6 fall into two major groups:
vinylogous porphyrins or platyrins (e.g. 1), which have
more than four total linking atoms between the four
pyrrole units,7,8 and higher order systems built up from
at least five pyrrolic or related subunits (Chart 1).1 The
first example of the latter category, sapphyrin (2), was
† Part 37 in the series “Conjugated Macrocycles Related to the
Porphyrins”. For part 36, see: Bergman, K. M.; Ferrence, G. M.; Lash,
T. D. J. Org. Chem. 2004, 69, 8851-8864.
* To whom correspondence should be addressed.
(1) Johnson, A. W. In Porphyrins and Metalloporphyrins; Smith, K.
M., Ed.; Elsevier: Amsterdam, The Netherlands, 1975; pp 729-754.
(2) Ayub, J.; Dolphin, D. Chem. Rev. 1997, 97, 2267-2340.
(3) Sessler, J. L.; Weghorn, S. J. Expanded, Contracted and Isomeric
Porphyrins; Elsevier: Oxford, UK, 1997.
(4) Sessler, J. L.; Gebauer, A.; Weghorn, S. J. In The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
Press: San Diego, CA, 2000; Vol. 2, pp 55-124.
(5) Lash, T. D. Angew. Chem., Int. Ed. 2000, 39, 1763.
(6) Sessler, J. L.; Seidel, D. Angew. Chem., Int. Ed. 2003, 42, 5134.
(7) (a) Berger, R. A.; LeGoff, E. Tetrahedron Lett. 1978, 19, 4225.
(b) LeGoff, E.; Weaver, O. G. J. Org. Chem. 1987, 52, 710.
(8) (a) Gosmann, M.; Franck, B. Angew. Chem., Int. Ed. Engl. 1986,
25, 1100. (b) Knubel, G.; Franck, B. Angew. Chem., Int. Ed. Engl. 1988,
27, 1170. (c) Franck, B.; Nonn, A. Angew. Chem., Int. Ed. Engl. 1995,
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reported by Woodward in 1966 at the Aromaticity Con-
ference in Sheffield in the United Kingdom.9-11 In rela-
tion to the Harvard group’s early studies on the total
synthesis of Vitamin B12,12 tetrapyrrole 3 was treated
with formic acid and HBr in an attempt to produce the
10.1021/jo040239o CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/06/2004
8842
J. Org. Chem. 2004, 69, 8842-8850

Synthesis of Sapphyrins
SCHEME 1
this pentapyrrolic system that had not previously been
recognized.11 The aromatic character of sapphyrins was
the focus of much of the early work,1 but metalation
studies had been largely unsuccessful.10 Sessler and co-
workers demonstrated that sapphyrins were versatile
anion binding systems, a feature that had not previously
been recognized for expanded porphyrin systems.18,19
Sapphyrins are also singlet-oxygen-producing photosen-
sitizers20 and have been explored for potential applica-
tions in photodynamic therapy21 and viral photoeradica-
tion.22 New routes to sapphyrins have been reported
where oxidative ring closure takes place to generate the
direct pyrrole-pyrrole linkage.23-25 In addition, meso-
tetrasubstituted sapphyrins and heterosapphyrins have
been produced in moderate yields by using variations on
Rothemund-type chemistry.26
SCHEME 2
We have explored alternative ways of modifying the
porphyrin system by replacing one or more of the usual
pyrrole rings with carbocyclic units.27,28 Much of this work
has made use of the “3 + 1” methodology,29,30 where a
tripyrrane is condensed with carbocyclic dialdehydes to
afford carbaporphyrinoids such as 7 or 8 (Chart 2).31,32
True carbaporphyrins (e.g. 7) retain strong diatropic ring
currents and the proton NMR spectra show the internal
CH resonance at -7 ppm.31,33,34 These porphyrin ana-
corresponding corrole 4 (Chart 1).10 However, the pen-
tapyrrolic sapphyrin system was generated instead,
albeit in low yield, as a beautiful blue glass.10 Due to this
intense blue color, Woodward proposed the name sap-
phyrin for this system.10,13 The sapphyrins are generally
isolated as diprotonated salts and give deep green solu-
tions in dichloromethane with a Soret band at 458 nm.10
Johnson and co-workers subsequently reported a rational
synthesis of sapphyrins and related heteroanalogues
using a “3 + 2” version of the MacDonald condensation
(Scheme 1) or a related sulfur extrusion strategy.14,15
Details of the work conducted by Woodward and his
collaborators were not published until 1983,10 but this
paper describes independent rational syntheses of sap-
phyrins with both a “3 + 2” strategy similar to Johnson’s
work and a “4 + 1” approach.10 In the latter method
(Scheme 2), tetrapyrrole 3 was reacted with 3,4-dimeth-
ylpyrrole-2,5-dicarbaldehyde (5) in the presence of 88%
formic acid to give sapphyrin 6 in modest yield.10 Interest
in the sapphyrin system was later revived by Sessler and
co-workers in the early 1990s.11,16,17 This group also used
the “3 + 2” methodology, but explored many features of
(17) (a) Sessler, J. L.; Cyr, M. J.; Burrel, A. K. Tetrahedron 1992,
48, 9661. (b) Sessler, J. L.; Hoehner, M. C.; Gebauer, A.; Andrievsky,
A.; Lynch, V. J. Org. Chem. 1997, 62, 9251. (c) Lisowski, J.; Sessler,
J. L.; Lynch, V. Inorg. Chem. 1995, 34, 3567.
(18) Sessler, J. L.; Davis, J. M. Acc. Chem. Res. 2001, 34, 989.
(19) Furuta, H.; Cyr, M. J.; Sessler, J. L. J. Am. Chem. Soc. 1991,
113, 6677. Kral, V.; Furuta, H.; Shreder, K.; Lynch, V.; Sessler, J. L.
J. Am. Chem. Soc. 1996, 118, 1595. Sessler, J. L.; Andrievsky, A. J.
Chem. Soc., Chem. Commun. 1996, 1119.
(20) Maiya, B. G.; Cyr, M.; Harriman, A.; Sessler, J. L. J. Phys.
Chem. 1990, 94, 3597.
(21) (a) Bonnett, R. Chem. Soc. Rev. 1995, 24, 19. (b) Pandey, R. K.;
Zheng, G. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M.,
Guilard, R., Eds.; Academic Press: San Diego, CA, 2000; Vol. 6, pp
157-230.
(22) Judy, M. M.; Matthews, J. L.; Newman, J. T.; Skiles, H. L.;
Boriack, R. L.; Sessler, J. L.; Cyr, M.; Maiya, B. G.; Nichol, S. T.
Photochem. Photobiol. 1991, 53, 101.
(23) Paolesse, R.; Licoccia, S.; Spagnoli, M.; Boschi, T.; Khoury, R.
G.; Smith, K. M. J. Org. Chem. 1997, 62, 5133.
(24) Sessler, J. L.; Shevchuk, S.; Davis, J. M. Tetrahedron Lett. 2001,
42, 2447.
(25) Simkhovich, L.; Rosenberg, S.; Gross, Z. Tetrahedron Lett. 2001,
42, 4929.
(9) Woodward’s announcement on the synthesis of the sapphyrin
system at the 1966 Aromaticity Conference in Sheffield is consistently
acknowledged in the literature10,11,15 but no mention of this ac-
complishment is made in the published proceedings for this meeting.
(10) Bauer, V. J.; Clive, D. R.; Dolphin, D.; Paine, J. B., III; Harris,
F. L.; King, M. M.; Loder, J.; Wang, S.-W. C.; Woodward, R. B. J. Am.
Chem. Soc. 1983, 105, 6429.
(26) (a) Rachlewicz, K.; Sprutta, N.; Latos-Grazynski, L.; Chmielews-
ki, P. J.; Szterenberg, L. J. Chem. Soc., Perkin Trans. 2 1998, 959. (b)
Bru¨ckner, C.; Sternberg, E. D.; Boyle, R. W.; Dolphin, D. Chem.
Commun. 1997, 1689. (c) Narayan, S. J.; Sridevi, B.; Chandrashekar,
T. K.; Vij, A.; Roy, R. Angew. Chem., Int. Ed. 1998, 37, 3394. (d)
Srinivasan, A.; Pushpan, S. K.; Kumar, M. R.; Mahajan, S.; Chan-
drashekar, T. K.; Roy, R.; Ramamurthy, P. J. Chem. Soc., Perkin Trans.
2 1999, 961.
(11) Sessler, J. L.; Cyr, M. J.; Burrell, A. K. Synlett 1991, 127.
(12) Woodward, R. B. Pure Appl. Chem. 1973, 33, 145.
(27) Lash, T. D. Synlett 2000, 279.
(13) Porphyrins are nearly always isolated as purple crystalline
materials and Hoppe-Seyler coined the name hematoporphyrin for the
purple substance derived by treating hemoglobin with aqueous sulfuric
acid from the Greek for blood and purple: Hoppe-Seyler, F. Med.-Chem.
Unters. 1871, 4, 531 and 540. Similarly, chlorin, the parent hydropor-
phyrin structure for the chlorophylls, takes its name from the Greek
word chloris for green. Woodward proposed the term sapphyrin by
analogy to the names of these “Pigments of Life” and similarly used
the name smaragdyrin (from the Greek word for emerald) for the
related norsapphyrins.10 The use of color-related names for expanded
porphyrins was later further popularized by Sessler and other re-
searchers in the field.3,4,6
(28) Lash, T. D. In The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic Press: San Diego, CA, 2000; Vol.
2, pp 125-199.
(29) (a) Lash, T. D. Chem. Eur. J. 1996, 2, 1197. (b) Lash, T. D. J.
Porphyrins Phthalocyanines 1997, 1, 29.
(30) The “3 + 1” designation refers to the number of pyrrole rings
(or surrogates) in each of the components used for these syntheses. In
the work discussed here, the “3 + 1”, “3 + 2”, and “4 + 1” methods are
all based upon the MacDonald “2 + 2” condensation where a dipyrryl-
methane is condensed with a dipyrrylmethane dialdehyde: Arsenault,
G. P.; Bullock, E.; MacDonald, S. F. J. Am. Chem. Soc. 1960, 82, 4384.
(31) Lash, T. D.; Hayes, M. J. Angew. Chem., Int. Ed. Engl. 1997,
36, 840.
(14) Broadhurst, M. J.; Grigg, R.; Johnson, A. W. J. Chem. Soc.,
Chem. Commun. 1969, 23.
(32) Lash, T. D.; Chaney, S. T. Angew. Chem., Int. Ed. Engl. 1997,
36, 839.
(33) Lash, T. D.; Hayes, M. J.; Spence, J. D.; Muckey, M. A.;
Ferrence, G. M.; Szczepura, L. F. J. Org. Chem. 2002, 67, 4860.
(34) Liu, D.; Lash, T. D. J. Org. Chem. 2003, 68, 1755.
(15) Broadhurst, M. J.; Grigg, R.; Johnson, A. W. J. Chem. Soc.,
Perkin Trans. 1 1972, 2111.
(16) Sessler, J. L.; Cyr, M. J.; Lynch, V.; McGhee, E.; Ibers, J. A. J.
Am. Chem. Soc. 1990, 112, 2810.
J. Org. Chem, Vol. 69, No. 25, 2004 8843

Richter and Lash
CHART 2
SCHEME 3
logues also exhibit unique chemical properties undergo-
ing unusual oxidation reactions35 and acting as superior
organometallic ligands for silver(III) and gold(III).36 In
contrast, azuliporphyrins 8 show reduced aromatic char-
acter due to the presence of a cross-conjugated azulene
subunit.32,37 However, this system also has interesting
chemistry38,39 and acts as an effective ligand for nickel-
(II), palladium(II), and platinum(II).40 In other work, we
have prepared modified systems by fusing aromatic rings
to the porphyrin nucleus.41-46 Although some of these
systems (e.g. phenanthroporphyrins 942,43) show only
small changes in their spectroscopic properties, acenaph-
thoporphyrins (e.g. 10) have highly red-shifted UV-vis
spectra and give strong absorptions in the far-red re-
gion.44,45 These compounds are also readily synthesized
by application of the “3 + 1” methodology.29 As this
approach had been so successful, we were interested in
synthesizing sapphyrin analogues using the same general
principles. Apart from the early study by Woodward’s
group on the synthesis of decaalkylsapphyrin 6,10 the “4
+ 1” route to sapphyrins had not seen any significant
applications. An improved route to the required tetra-
pyrrole intermediate 11 (Scheme 3) had been developed
by Sessler and co-workers in relation to their synthesis
of rubyrins,47 and the availability of this compound
together with our extensive experience with the “3 + 1”
methodology has allowed the synthesis of novel sapphy-
rin-type structures. These include new macrocyclic sys-
tems with fused phenanthrene and acenaphthylene units,
as well as carbasapphyrins and an azulisapphyrin.48,49
Results and Discussion
Bipyrrole 1250 was reacted with 2 equiv of acetoxy-
methylpyrrole 13 in refluxing acetic acid-ethanol to give
the corresponding tetrapyrrolic dibenzyl ester 11a in 74%
yield (Scheme 3). The proton NMR spectrum for 11a was
essentially identical with the data reported previously
by Sessler et al.47 It is noteworthy, however, that the
bridging methylenes in 11a produce a broad 4H singlet
at 3.7 ppm, while the benzyl ester OCH2 groups are
shifted upfield from a typical value of 5.3 ppm to give a
broad 4H resonance at 4.6 ppm. Similar effects are
(35) (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.
(36) (a) Muckey, M. A.; Szczepura, L. F.; Ferrence, G. M.; Lash, T.
D. Inorg. Chem. 2002, 41, 4840. (b) Lash, T. D.; Rasmussen, J. M.;
Bergman, K. M.; Colby, D. A. Org. Lett. 2004, 6, 549.
(37) (a) Graham, S. R.; Colby, D. A.; Lash, T. D. Angew. Chem., Int.
Ed. 2002, 41, 1371. (b) Colby, D. A.; Lash, T. D. Chem. Eur. J. 2002,
8, 5397. (c) Lash, T. D.; Colby, D. A.; Ferrence, G. M. Eur. J. Org.
Chem. 2003, 4533.
(47) Sessler, J. L.; Morishima, T.; Lynch, V. Angew. Chem., Int. Ed.
Engl. 1991, 30, 977.
(48) Preliminary communications: (a) Lash, T. D.; Richter, D. T. J.
Am. Chem. Soc. 1998, 120, 9965. (b) Richter, D. T.; Lash, T. D.
Tetrahedron Lett. 1999, 40, 6735.
(38) Lash, T. D. Chem. Commun. 1998, 1683.
(39) Colby, D. A.; Ferrence, G. M.; Lash, T. D. Angew. Chem., Int.
Ed. 2004, 43, 1346.
(40) (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.
(49) These results were presented, in part, at the following meet-
ings: 89th Annual Meeting of the Illinois State Academy of Science,
Illinois Wesleyan University, Bloomington, IL, October 1996 (Richter,
D. T.; Lash, T. D. Transactions of the Illinois State Academy of Science;
1996; Supplement to Vol. 89, p 55, Abstract No. 47); 213th National
ACS Meeting, San Francisco, CA, April 1997 (Richter, D. T.; Lash, T.
D. Book of Abstracts; American Chemical Society: Washington, DC,
1997; CHED 439); 31st Great Lakes Regional ACS Meeting, University
of Wisconsin-Milwaukee, June 1998 (Richter, D. T.; Lash, T. D.
Program and Abstracts; Abstract No. 190); 216th National ACS
Meeting, Boston, MA, August 1998 (Richter, D. T.; Lash, T. D. Book
of Abstracts; American Chemical Society: Washington, DC, 1998;
ORGN 593); 31st Central Regional ACS Meeting, Ohio State Univer-
sity, Columbus, OH, June 1999 (Richter, D. T.; Lash, T. D. Program
and Abstracts; Abstract No. 265).
(41) Lash, T. D. J. Porphyrins Phthalocyanines 2001, 5, 267.
(42) Lash, T. D.; Novak, B. H. Angew. Chem., Int. Ed. Engl. 1995,
34, 683.
(43) (a) Lash, T. D.; Novak, B. H. Tetrahedron Lett. 1995, 36, 4381.
(b) Novak, B. H.; Lash, T. D. J. Org. Chem. 1998, 63, 3998.
(44) (a) Chandrasekar, P.; Lash, T. D. Tetrahedron Lett. 1996, 37,
4873. (b) Lash, T. D.; Chandrasekar, P.; Osuma, A. T.; Chaney, S. T.;
Spence, J. D. J. Org. Chem. 1998, 63, 8455.
(45) (a) Lash, T. D.; Chandrasekar, P. J. Am. Chem. Soc. 1996, 118,
8767. (b) Spence, J. D.; Lash, T. D. J. Org. Chem. 2000, 65, 1530.
(46) (a) Lin, Y.; Lash, T. D. Tetrahedron Lett. 1995, 36, 9441. (b)
Lash, T. D.; Gandhi, V. J. Org. Chem. 2000, 65, 8020. (c) Lash, T. D.;
Werner, T. M.; Thompson, M. L.; Manley, J. M. J. Org. Chem. 2001,
66, 3152.
(50) Sessler, J. L.; Hoehner, M. C. Synlett 1994, 211.
8844 J. Org. Chem., Vol. 69, No. 25, 2004

Synthesis of Sapphyrins
SCHEME 4
commonly noted for tripyrranes and have been attributed
to these oligopyrroles taking on a helical conformation
in solution.29,51 This conformational preference is believed
to be beneficial to macrocycle formation and allows
excellent yields to be obtained without the necessity of
using high-dilution techniques.29 Cleavage of the benzyl
ester protective groups with hydrogen over 10% pal-
ladium-charcoal gave the corresponding dicarboxylic
acid 11b and this was used in crude form for sapphyrin
synthesis.
Initial studies were carried out on the synthesis of the
known sapphyrin 1417a from 11b and pyrrole dialdehyde
15 (Scheme 3). In all of these condensations, including
the “3 + 1”, “3 + 2”, and “4 + 1” methodologies, an
oxidation step is necessary. Tetrapyrrole 11b was treated
with TFA, diluted with dichloromethane and condensed
with dialdehyde 15. The solution was then neutralized
with triethylamine and the reaction mixture oxidized
with 1 equiv of DDQ. Following extraction, the solutions
were washed with hydrochloric acid to generate the
dihydrochloride salt. After chromatography, the sapphy-
rin was obtained as a blue glass and recrystallization
from chloroform-hexanes gave 14 in 36% yield.48a In a
typical “3 + 2” synthesis, tripyrrane is condensed with
bipyrroledialdehyde in the presence of p-toluenesulfonic
acid, and following O2 oxidation over a period of 18 h,
sapphyrin 14 can be isolated in 44% yield.17a Hence, our
method compares favorably with alternative routes to
this system. Unfortunately, our studies gave the related
sapphyrin systems discussed below in inferior yields and
we speculated that the use of DDQ as an oxidant gave
rise to significant degradation. In other studies, we had
used dilute solutions of aqueous ferric chloride as an
oxidant.52 This proved to be an excellent reagent for these
“4 + 1” syntheses and gave much improved yields of
sapphyrin products.48b The reaction solution is placed in
a separatory funnel and shaken vigorously for 5-10 min
with a 0.1% w/v solution of ferric chloride in water. With
use of this simple method, sapphyrin 14 was obtained in
50% yield. For all of the systems described below, even
larger improvements in the yields were noted.
Oxasapphyrin 16 and thiasapphyrin 17 were previ-
ously prepared in 26% and 36% yields, respectively, using
the “3 + 2” methodology.17a By using our conditions with
ferric chloride as the oxidant, reaction of 11b with 2,5-
furandialdehyde 18a gave 16 as the dihydrochloride salt
in 68% yield. Similarly, condensation of 11b with
thiophene dialdehyde 18b afforded thiasapphyrin 17 in
a remarkable 90% yield. Hence, the ferric chloride
conditions represent an important innovation for the
synthesis of sapphyrin-type systems. Sapphyrin 14 and
heterosapphyrins 16 and 17 all show strong Soret bands
near 460 nm in their UV-vis spectra, and are highly
diatropic reflecting the presence of 22π electron delocal-
ization pathways within these structures. The proton
NMR spectrum of 12‚2HCl shows three resonances for
the five NH protons between -4 and -5 ppm, while the
external meso-protons are deshielded giving rise to two
singlets near 11.7 ppm. As the properties of these systems
have been examined in detail by others,10,15,17 further
details will not be repeated in this paper.
The success of the “4 + 1” method enabled us to
consider the synthesis of new types of sapphyrin struc-
tures. Fusion of a phenanthrene unit to the porphyrin
chromophore leads to very small changes in the UV-vis
spectra,42,43 but acenaphthylene gives much larger ba-
thochromic shifts.44,45 In addition, free base monoacenaph-
thoporphyrins 10 (Chart 2) give three Soret bands44 while
phenanthroporphyrins 9 afford a single strong absorption
in this region.43 To see whether these structural units
have the same effects in the sapphyrin series, the ring-
fused sapphyrins 19 and 20 were targeted for synthesis
(Scheme 4).53 Reaction of 11b with phenanthropyrrole
dialdehyde 21,44b followed by oxidation with DDQ, gave
phenanthrosapphyrin 19 in a respectable 33% yield,
although acenaphthopyrrole dialdehyde 2244b reacted
with 11b to give acenaphthosapphyrin 20 in only 16%
yield. However, when aqueous ferric chloride was used
as the oxidant, the yields increased to 75% and 74%,
respectively. The free base spectrum of phenanthrosap-
phyrin 19 in 1% Et3N-CHCl3 gave a Soret band at 473
nm (Figure 1), significantly shifted compared to the
spectrum for 14, which gave the corresponding band at
457 nm under these conditions. Acenaphthosapphyrin 20
gave a more complex Soret band region with the strongest
band at 500 nm (Figure 1). The Q-bands for 20 were also
slightly red shifted compared to those for 19. The
protonated forms in chloroform gave Soret bands at 474
and 486 nm for 19 and 20, respectively, and the longest
wavelength Q-band for 20 appeared at 710 nm compared
to a value of 697 nm for 19. The data demonstrate that
the acenaphthylene unit has a stronger effect on the
sapphyrin chromophore than phenanthrene, and like
acenaphthoporphyrins 10,44 20 shows a split Soret band
region for the free base structure. However, phenan-
threne has a much larger effect on the sapphyrin chro-
mophore than it does for regular porphyrins,43 and the
difference between the two sapphyrin systems is much
reduced. The diatropic ring current for 19 and 20 is
undiminished, and the meso-protons showed up as two
2H singlets for both systems at >11.6 ppm for the proton
NMR spectra in TFA-CDCl3, while the NHs resonated
between -5 and -6.2 ppm. The proton and carbon-13
(51) Jiao, W.; Lash, T. D. J. Org. Chem. 2003, 68, 3896.
(52) Lash, T. D.; Richter, D. T.; Shiner, C. M. J. Org. Chem. 1999,
64, 7973.
(53) The first syntheses of benzosapphyrins using the “3 + 2”
MacDonald route has recently been reported: Ono, N.; Kuroki, K.;
Watanabe, E.; Ochi, N.; Uno, H. Heterocycles 2004, 62, 365.
J. Org. Chem, Vol. 69, No. 25, 2004 8845

Richter and Lash
FIGURE 2. Upfield and downfield regions for the 400-MHz
proton NMR spectra of benzocarbasapphyrin 24: (A) mono-
cation in CDCl3 and (B) C-protonated dication on TFA-CDCl3.
FIGURE 1. UV-vis spectra of ring-fused sapphyrins in 1%
triethylamine-chloroform: (A) free base phenanthrosapphyrin
19 and (B) free base acenaphthosapphyrin 20.
and this was isolated as blue crystals after recrystalli-
zation from chloroform-hexanes. The UV-vis spectrum
of 24‚HCl in chloroform gave a Soret band at 476 nm,
with a secondary band at 496 nm and a series of Q-bands
at 613, 669, 708, and 788 nm. In 1% pyridine-chloroform,
the spectrum was essentially unaltered, while solutions
in 1% triethylamine-chloroform appeared to correspond
to a mixture of the free base and protonated forms. By
using 1% DBU-chlorofrom, the free base spectrum could
be obtained and this showed a Soret band at 470 nm and
Q-bands at 596, 645, 710, and 793 nm. The free base form
was unstable and gradually degraded in solution. Addi-
tion of 1% TFA to chloroform solutions of 24‚HCl gave
rise to a new species assigned as the dication 24H22+. This
gave a very strong Soret band at 482 nm and several
minor bands at longer wavelengths. The 400 MHz proton
NMR spectrum of 24‚HCl in CDCl3 demonstrated that
the macrocycle has overall aromatic character and the
internal CH gave a broadened 1H singlet at -7.9 ppm
while the NHs afforded two broad 2H singlets at -5.1
and -4.4 ppm (Figure 2). The exterior meso-protons are
also strongly deshielded giving two 2H singlets at 11.1
and 11.3 ppm. The methyl groups are indirectly affected
by the aromatic ring current, and can provide a useful
measure of the aromatic character. Porphyrin methyl
groups generally resonate at 3.6 ppm,54 while sapphyrin
14‚2HCl gave singlets at 4.1 and 4.2 ppm. It is signifi-
cant, therefore, that 24‚HCl gave two 6H resonances near
4.1 ppm. Addition of one drop of TFA to the NMR tube
gave the C-protonated dication 24H22+. Carbaporphyrins
7 also give rise to C-protonated dications,31,33 but these
are only favored in 50% TFA-chloroform. The heightened
SCHEME 5
NMR spectra also demonstrate that these molecules
retain a plane of symmetry.
Reaction of 11b with diformylindene 23, followed by
oxidation with DDQ, gave benzocarbasapphyrin 24 as the
monohydrochloride salt in 18% yield (Scheme 5). Again,
using ferric chloride as the oxidant gave much improved
yields and carbasapphyrin 24‚HCl was isolated under
these conditions in 38% yield. Unlike most sapphyrins
and heterosapphyrins, carbasapphyrin 24 only has one
imine-type nitrogen that can be protonated. Prior to
purification, the reaction solution was washed with 10%
hydrochloric acid to give the stable protonated form 24H+
(54) Medforth, C. J. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego, CA, 2000;
Vol. 5, pp 1-80.
8846 J. Org. Chem., Vol. 69, No. 25, 2004

Synthesis of Sapphyrins
SCHEME 6
FIGURE 3. UV-vis spectra of carbasapphyrin 26: dotted
line, monocation in chloroform; bold line, C-protonated dication
in 2% TFA-chloroform.
ability of the larger sapphyrin system to delocalize the
positive charges is no doubt responsible for the increased
ease of C-protonation in this case.55 This species is also
aromatic, although the diatropicity is somewhat reduced.
The interior CH2 gives a resonance at -3.75 ppm, while
the NH protons produce two broad 2H singlets at -0.56
and +0.67 ppm (Figure 2). More telling is the upfield shift
of the meso-protons to 10.37 (2H, s) and 11.05 (2H, s)
ppm, while the methyl groups now produce two 6H
singlets at 3.43 and 3.66 ppm. We believe that the
macrocyclic ring current must be relocated through the
benzene unit (shown in bold), and this idea is supported
by the downfield shifts for the benzo-protons. In the
monocation, the benzo-protons gave two 2H multiplets
at 7.96 and 9.35 ppm, but these resonances appear at
band at 480 nm, and Q-bands at 612, 671, 755, and 844
nm (Figure 3). In 2% TFA-chloroform, the Soret band
2+
for 26H2 is split into two absorptions at 469 and 490
nm, while a series of weaker Q-bands are present at 632,
685, and 745 nm (Figure 3). The proton NMR spectrum
of 26‚HCl in CDCl3 shows that the ring current is
undiminished, giving a resonance for the internal CH at
-8.5 ppm, while the NHs appear between -4.7 and -5.6
ppm. Addition of TFA afforded dication 26H22+, and this
showed a similarly strong ring current with the internal
CH2 producing a 2H singlet at -7.1 ppm. The monocation
gave four 3H singlets for the methyl groups between 4.0
2+
and 4.1 ppm, while 26H2 gave these between 3.8 and
4.1 ppm. The meso-protons for the dication were shifted
downfield beyond 11 ppm for 26H22+, while the mono-
cation gave these in the range of 10.7 to 11.3 ppm. The
increased aromatic character for diprotonated 26 com-
pared to the dication for benzocarbasapphyrin 24 is
probably due to two factors. First, the benzene ring in
24 loses some of its aromatic character by using two of
its carbons in the 22π electron delocalization pathway
and this decreases the favorability of this species. Second,
the formyl moiety is electron withdrawing and this helps
to stabilize the diprotonated species. Similar trends have
previously been noted for carbaporphyrin systems.33
Azulene dialdehyde 27 was also reacted with 11b in
TFA-CH2Cl2, and following oxidation with aqueous ferric
chloride, the novel azulisapphyrin system 28 was isolated
as the dihydrochloride salt in 35% yield (Scheme 7). The
UV-vis spectrum for 28‚2HCl in chloroform showed four
absorptions in the Soret band region at 420, 455, 481,
and 511 nm, and a broad absorption at 742 nm (Figure
4). This resembles the UV-vis spectrum reported for the
free base form of azuliporphyrin 8.32 Addition of TFA led
to minor shifts in these bands but the spectra appeared
to correspond to the same species. In neat pyridine,
essentially the same spectrum was obtained indicating
that the azulisapphyrin system is considerably more
basic than pyridine. However, addition of 1% triethy-
lamine gave rise to a new species tentatively assigned
as the free base form with Soret-like bands at 417 and
454 nm. This species proved to be rather unstable and
after a few minutes the initially formed species dis-
appeared and the spectrum only showed broad absorption
features. Surprisingly, addition of TFA regenerated the
2+
8.72 and 10.00 for 24H2 in TFA-CDCl3. As expected,
addition of three drops of d-TFA to a solution of 24‚HCl
in CDCl3 led to the immediate exchange of the internal
CH and NH protons. This is observed for carbaporphyrins
7 as well, but these also show slow exchange at the meso-
positions. However, even after several days at room
temperature, no exchange could be observed at the meso-
positions for 24. This result demonstrates that C-proto-
nation does not occur at the meso-carbons for the
carbasapphyrin system. Attempts to obtain a proton
NMR spectrum for the free base form of 24 were largely
unsuccessful, apparently due to the low stability of this
species. However, a poor quality proton NMR spectrum
of 24 was obtained in d5-pyridine and this showed the
internal CH at -5 ppm.
Cyclopentadiene trialdehyde 25 has been used to
prepare carbaporphyrins with use of the “3 + 1” ap-
proach, although the yields were typically in the range
of 5-7%.31,33,56 Reaction with 25 with 11b in TFA-CH2-
Cl2, followed by ferric chloride oxidation, gave the car-
basapphyrin aldehyde 26 in 7-12% yield (Scheme 6). The
low yields are most likely due to the presence of an extra
aldehyde unit that can lead to unwanted side reactions.
However, this chemistry gave sufficient material to
characterize the formylcarbasapphyrin 26. The UV-vis
spectrum for 26‚HCl in chloroform gave a broad Soret
(55) A dicarbaporphyrin system also readily underwent C-protona-
tion, although in this case a monocation was generated: Lash, T. D.;
Romanic, J. L.; Hayes, M. J.; Spence, J. D. Chem. Commun. 1999, 819.
(56) Berlin, K. Angew. Chem., Int. Ed. Engl. 1996, 35, 1820.
J. Org. Chem, Vol. 69, No. 25, 2004 8847

Richter and Lash
SCHEME 8
FIGURE 4. UV-vis spectra of azulisapphyrin 28: dotted line,
dication in chloroform; bold line, pyrrolidine adduct 30 in 1%
pyrrolidine-chloroform.
SCHEME 7
SCHEME 9
for 28 in various solvents were poorly resolved but these
all indicated that the protonated system was highly
diatropic. As is the case for protonated azuliporphy-
rins,32,37 the aromatic character is believed to be derived
from favorable canonical forms with a combination of
tropylium and carbaporphyrinoid character (e.g. reso-
nance contributor 28a). In d4-methanol, the internal CH
proton resonated at -8.2 ppm, while the meso-protons
gave two 2H singlets at 10.1 and 10.7 ppm. However,
these shifts were very solvent dependent. For instance,
the interior CH showed up at -3.2 ppm in d5-pyridine-
CDCl3 and -4.8 ppm in TFA-CDCl3. Many of the same
trends are evident for azulisapphyrins and azuliporphy-
rins, but the instability of the free base form of 28, as
well as the difficulties in obtaining high-quality NMR
spectra, has severely limited these studies.
Several other dialdehydes were reacted with 11b, but
difficulties were encountered in isolating these sapphyrin
products. For instance, 3-hydroxypyridine-2,6-dicarb-
aldehyde (31a)57 reacted with 11b to give a nonaromatic
product tentatively assigned as 32 (Scheme 9). This
structure was supported by high-resolution mass spec-
trometry, but difficulties have been encountered in
obtaining NMR data for this system. The related benzene
dialdehyde 31b failed to give any macrocyclic product,
even though reactions with tripyrranes afford aromatic
oxybenziporphyrins.58,59 Therefore, there appears to be
some limitations to the modifications that are possible
for the sapphyrin system.
original diprotonated species. We speculate that nucleo-
philic attack was taking place at the meso-carbons and
this was reversible under acidic conditions. When the
spectrum was run in 1% DBU-dichloromethane, the free
base species showed greater stability although degrada-
tion still occurred over a 30-min period. The free base
form gave bands at 415, 457, 490, and 525 nm and a
broad band centered on 781 nm. The degradation was
not reversible under these conditions and addition of TFA
did not produce any recognizable features in the resulting
UV-vis spectrum. Azuliporphyrins 8 reversibly react
with nucleophiles such as pyrrolidine to give adducts (e.g.
29) which take on full carbaporphyrin aromaticity (Scheme
8).37,38 This reactivity is believed to act as a trigger in
oxidative rearrangements of azuliporphyrins to produce
benzocarbaporphyrins.37,38 Addition of 1% pyrrolidine to
a solution of 28 in chloroform immediately gave rise to a
species with a strong Soret band at 480 nm, followed by
a series of Q-bands that extended to 834 nm (Figure 4).
This species is assigned as the pyrrolidine-carbasap-
phyrin adduct 30 (Scheme 8). Unfortunately, this species
undergoes irreversible decomposition over a period of
about 20 min at room temperature. The NMR spectra
(57) Lash, T. D.; Chaney, S. T. Chem. Eur. J. 1996, 2, 944.
(58) Lash, T. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2533.
(59) (a) Lash, T. D.; Chaney, S. T.; Richter, D. T. J. Org. Chem. 1998,
63, 9076. (b) Richter, D. T.; Lash, T. D. Tetrahedron 2001, 57, 3659.
8848 J. Org. Chem., Vol. 69, No. 25, 2004

Synthesis of Sapphyrins
668 (4.11), 711 nm (3.84); UV-vis (CHCl3) λmax (log ꢀ) 433
(4.61), 457 (5.63), 578 (3.43), 624 (4.03), 675 (4.21), 689 nm
(4.13); 1H NMR (CDCl3) δ -4.90 (2H, s), -4.57 (1H, s), -4.29
(2H, s), 2.17-2.23 (12H, two overlapping triplets), 2.30 (6H,
t, J ) 7.6 Hz), 4.11 (6H, s), 4.22 (6H, s), 4.55 (4H, q, J ) 7.6
Hz), 4.67-4.78 (8H, two overlapping quartets), 11.63 (2H, s),
11.70 (2H, s); hr ms calcd for C40H50N5 600.4066, found
600.4064.
Conclusions
The “4 + 1” methodology is shown to be a flexible and
high-yielding route to sapphyrins, heterosapphyrins, and
carbasapphyrins. These types of aromatic macrocycles
have attracted considerable interest, in part due to their
anion binding characteristics. The “4 + 1” route, together
with the mild ferric chloride oxidation conditions, allows
the synthesis of unusual carbasapphyrin structures
including the first example of an azulisapphyrin system.
Although the route has some limitations, it provides the
means to examine whether the trends previously ob-
served for porphyrin systems also apply to the sapphy-
rins.
3,7,18,22-Tetraethyl-2,8,17,23-tetramethyl-27-oxasap-
phyrin (16). The oxasapphyrin was prepared by the previous
procedure from 11b (25 mg) and 2,5-furandicarbaldehyde (6
mg). The crude product was chromatographed on silica with
15% methanol-chloroform and the product eluted as a blue-
green fraction. Recrystallization of the dihydrochloride salt
from chloroform-hexanes afforded the oxasapphyrin 16‚2HCl
as blue crystals (19 mg, 68%), mp >300 °C; UV-vis (1% TFA-
CHCl3) λmax (log ꢀ) 454 (5.56), 608 (3.95), 627 (4.13), 666 (4.05),
Experimental Section
1
692 nm (4.01); H NMR (CDCl3) δ -0.25 (4H, s), 1.84 (6H, t,
Tetrapyrrole Dibenzyl Ester 11a. Diethyl 4,4′-diethyl-
3,3′-dimethyl-2,2′-bipyrroledicarboxylate50 (1.80 g) was heated
to reflux in ethylene glycol (41 mL) with NaOH (410 mg) and
8 drops of hydrazine under nitrogen for 2 h. The solution was
cooled to room temperature and diluted with water, followed
by extraction with chloroform and drying over sodium sulfate.
After the solvent was removed under reduced pressure, the
resulting residue was dissolved in ethanol (70 mL). To this
solution was added 2 equiv of acetoxymethylpyrrole 1360 (3.15
g) and acetic acid (7 mL) and the mixture was then stirred at
reflux overnight under nitrogen. The solution was then cooled
to 0 °C for 1 h, and the precipitate filtered and washed with
cold ethanol. The resulting light green solid was recrystallized
from chloroform/hexanes to give the desired product (2.58 g,
74%) as off-white crystals, mp 168-171 °C (lit. mp47 163-166
°C); 1H NMR (CDCl3) δ 0.87 (6H, t, J ) 7.1 Hz), 1.12 (6H, t, J
) 7.3 Hz), 2.03 (6H, s), 2.15 (6H, s), 2.4-2.5 (8H, m), 3.73 (4H,
br s), 4.62 (4H, br s), 6.92 (4H, br m), 7.19-7.27 (6H, m), 9.95
(2H, br s, NH), 11.01 (2H, br s, NH).
Tetrapyrroledicarboxylic Acid 11b. Tetrapyrrole di-
benzyl ester 11a (450 mg) was dissolved in THF (150 mL) and
shaken with 10% palladium-charcoal (127 mg) under an
atmosphere of hydrogen at 40 psi overnight. The solution was
filtered to remove the activated charcoal and the filtrate placed
on a rotary evaporator to remove the solvent. The resulting
dark blue residue was further dried under vacuum overnight
to remove traces of solvent. The residual dark blue powder
could then be scraped from the flask, yielding the diacid (350
mg; 94%). This was used without further purification.
3,8,12,13,17,22-Hexaethyl-2,7,18,23-tetramethylsapphy-
rin (14). In a 100-mL round-bottom flask, tetrapyrrole 11b
(27 mg) and TFA (1 mL) were stirred under nitrogen for 2 min,
after which dichloromethane (99 mL) was added, followed
immediately by pyrrole dialdehyde 1519b,61 (9 mg) and the
mixture was stirred overnight under nitrogen. The mixture
was then washed with water, and then vigorously shaken with
a 0.1% w/v aqueous FeCl3 solution (200 mL) for 5-10 min.
The organic phase was separated, adding saturated sodium
chloride solution if necessary to aid phase separation, and then
washed with water, saturated sodium bicarbonate solution,
and 10% hydrochloric acid. At each stage, back extractions
with chloroform were performed to minimize losses of sap-
phyrin product. The solvent was removed in vacuo, and the
resulting blue residue chromatographed on silica eluting with
9% methanol-chloroform. Upon evaporation of the solvent, the
product was obtained as a bright teal-blue solid. Recrystalli-
zation from chloroform-hexanes afforded the decaalkylsap-
phyrin 14‚2HCl as deep blue crystals (15 mg, 50%), mp >300
°C; UV-vis (1% Et3N-CHCl3) λmax (log ꢀ) 457 (5.45), 610 (3.88),
J ) 7.6 Hz), 1.98 (6H, t, J ) 7.6 Hz), 3.76 (6H, s), 3.82 (6H, s),
4.17 (4H, q, J ) 7.6 Hz), 4.27 (4H, q, J ) 7.6 Hz), 10.03 (2H,
s), 10.51 (2H, s), 10.61 (2H, s); 1H NMR (TFA-CDCl3) δ -6.03
(2H, s), -5.92 (2H, s), 2.11 (6H, t, J ) 7.8 Hz), 2.20 (6H, t, J
) 7.8 Hz), 4.16 (6H, s), 4.27 (6H, s), 4.55 (4H, q, J ) 7.6 Hz),
4.79 (4H, q, J ) 7.6 Hz), 11.02 (2H, s), 11.82 (2H, s), 11.88
(2H, s); fab hr ms calcd for C36H41N4O 545.3280, found
545.3280.
3,7,18,22-Tetraethyl-2,8,17,23-tetramethyl-27-thiasap-
phyrin (17). The thiasapphyrin was prepared by the previous
procedure from 11b (26 mg) and 2,5-thiophenedicarbaldehyde
(7 mg). The crude product was chromatographed on silica
eluting with 15% methanol-chloroform and the product col-
lected as the bright blue-green fraction. Recrystallization from
chloroform-hexanes yielded the thiasapphyrin dihydrochlo-
ride salt as bluish-purple crystals (27 mg, 90%), mp >300 °C;
UV-vis (1% TFA-CHCl3) λmax (log ꢀ) 464 (5.51), 644 (3.95),
689 nm (4.10); 1H NMR (CDCl3) δ 1.77 (6H, t, J ) 7.6 Hz),
1.96 (6H, t, J ) 7.6 Hz), 3.63 (6H, s), 3.74 (6H, s), 4.10 (4H, q,
J ) 7.6 Hz), 4.19 (4H, q, J ) 7.5 Hz), 10.36 (2H, s), 10.45 (2H,
s), 11.12 (2H, s); 1H NMR (TFA-CDCl3) δ -6.80 (2H, s), -5.51
(2H, s), 1.97 (6H, t, J ) 7.8 Hz), 2.19 (2H, t, J ) 7.8 Hz), 4.09
(6H, s), 4.25 (6H, s), 4.56 (4H, q, J ) 7.7 Hz), 4.75 (4H, q, J )
7.7 Hz), 11.36 (2H, s), 11.92 (2H, s), 12.48 (2H, s); fab hr ms
calcd for C36H41N4S 561.3052, found 561.3053.
3,7,18,22-Tetraethyl-2,8,17,23-tetramethylphenanthro-
[9,10-l]sapphyrin (19). The phenanthrosapphyrin was pre-
pared by the previous procedure from 11b (31 mg), phenan-
thropyrrole dialdehyde 2144b (24 mg), TFA (1 mL), and
dichloromethane (99 mL). Following the previous extraction
sequence, the resulting blue residue was chromatographed on
silica eluting with 8% methanol-chloroform and the product
collected as a bright teal-blue fraction. Recrystallization from
chloroform-hexanes afforded the phenanthrosapphyrin 19‚
2HCl as blue crystals (33 mg, 75%), mp >300 °C; UV-vis (1%
Et3N-CHCl3) λmax (log ꢀ) 473 (5.45), 607 (3.91), 626 (3.89), 659
(4.27), 686 (4.20), 726 (3.77), 750 nm (3.86); UV-vis (CHCl3)
λmax (log ꢀ) 474 (5.75), 589 (3.68), 639 (4.14), 697 nm (4.57); 1H
NMR (CDCl3) δ -2.82 (5H, br s), 1.87 (6H, t, J ) 7.5 Hz), 1.97
(6H, t, J ) 7.6 Hz), 3.74 (6H, s), 3.98 (6H, s), 4.20 (4H, q, J )
7.5 Hz), 4.42 (4H, q, J ) 7.4 Hz), 8.01 (2H, t, J ) 7.5 Hz), 8.24
(2H, t, J ) 7.2 Hz), 9.26 (2H, d, J ) 8.2 Hz), 10.10 (2H, d, J )
7.7 Hz), 10.35 (2H, s), 11.35 (2H, s); 1H NMR (TFA-CDCl3) δ
-5.61 (2H, s), -5.50 (2H, s), -5.02 (1H, s), 2.07 (6H, t, J )
7.8 Hz), 2.15 (6H, t, J ) 7.5 Hz), 4.11 (6H, s), 4.26 (6H, s),
4.53 (4H, q, J ) 7.6 Hz), 4.69 (4H, q, J ) 7.7 Hz), 8.26 (2H, t,
J ) 7.5 Hz), 8.47 (2H, t, J ) 7.2 Hz), 9.44 (2H, d, J ) 8.2 Hz),
10.38 (2H, d, J ) 7.6 Hz), 11.62 (2H, s), 12.57 (2H, s); 13C NMR
(CDCl3) δ 12.9, 16.0, 17.9, 18.0, 20.7, 20.8, 30.0, 95.3, 95.8,
124.7, 126.1, 127.1, 128.1, 128.5, 129.6, 132.2, 132.3, 133.3,
134.6, 135.2, 136.2, 140.3, 141.6; 13C NMR (TFA-CDCl3) δ
13.1, 15.6, 17.4, 17.6, 21.0, 21.2, 94.1, 98.5, 125.2, 128.2, 128.5,
(60) Johnson, A. W.; Kay, I. T.; Markham, E.; Price, R.; Shaw, K.B.
J. Chem. Soc. 1959, 3416.
(61) Tardieux, C.; Bolze, F.; Gros, C. P.; Guilard, R. Synthesis 1998,
267.
J. Org. Chem, Vol. 69, No. 25, 2004 8849

Richter and Lash
128.7, 129.4, 129.5, 130.8, 131.0, 132.6, 132.7, 133.5, 136.1,
136.9, 143.2, 144.9; hr ms calcd for C48H49N5 695.3988, found
695.3979.
diene63 (7 mg) with TFA (1 mL) in CH2Cl2 (99 mL). After the
solvent was removed under reduced pressure, the resulting
dark residue was chromatographed on silica eluting with 5%
methanol-chloroform and the product collected as a green
fraction. Recrystallization from chloroform-hexanes afforded
the formylcarbasapphyrin hydrochloride salt (4-5 mg, 7-12%)
as blue crystals, mp >300 °C; UV-vis (CHCl3; HCl-salt
monocation) λmax (log ꢀ) 400 (4.53), 480 (5.18), 612 (4.06), 671
(4.26), 755 (3.85), 844 nm (4.09); UV-vis (2% TFA-CHCl3;
dication) λmax (log ꢀ) 343 (4.45), 469 (5.41), 490 (5.29), 632
(4.12), 685 (4.13), 745 nm (3.98); 1H NMR (CDCl3) δ -8.10 (1H,
br s), -5.20 (2H, br s), -4.40 (1H, br s), -4.30 (1H, br s), 2.0-
2.1 (12H, four overlapping triplets), 4.02 (3H, s), 4.07 (3H, s),
4.09 (3H, s), 4.10 (3H, s), 4.47-4.54 (4H, two overlapping
quartets), 4.56-4.64 (4H, two overlapping quartets), 9.72 (1H,
s), 10.93 (1H, s), 11.04 (1H, s), 11.09 (1H, s), 11.26 (1H, s),
3,7,18,22-Tetraethyl-2,8,17,23-tetramethylacenaphtho-
[1,2-l]sapphyrin (20). The acenaphthosapphyrin was pre-
pared by the previous procedure from 11b (53 mg), acenaph-
thopyrrole dialdehyde 2244b (24 mg), TFA (1 mL), and
dichloromethane (99 mL). Following the previous extraction
sequence, the blue residue was chromatographed on silica
eluting with 8% methanol-chloroform and the product col-
lected as a bright teal-blue fraction. Recrystallization from
chloroform-hexanes afforded the acenaphthosapphyrin as
blue crystals (55 mg, 74%), mp >300 °C; UV-vis (1% Et3N-
CHCl3) λmax (log ꢀ) 500 (5.25), 677 (4.17), 709 (4.46), 744 nm
(4.27); UV-vis (CHCl3) λmax (log ꢀ) 486 (5.53), 595 (3.70), 647
(4.07), 710 nm (4.81); 1H NMR (CDCl3) δ -3.36 (5H, br s),
1.92-1.99 (12H, two overlapping triplets), 3.73 (6H, s), 3.87
(6H, s), 4.27-4.34 (8H, two overlapping quartets), 7.80 (2H,
t), 7.89 (2H, d, J ) 7.8 Hz), 8.75 (2H, d, J ) 5.3 Hz), 10.39
(4H, s); 1H NMR (TFA-CDCl3) δ -6.20 (2H, s), -5.80 (2H, s),
-5.55 (1H, s), 2.10 (6H, t, J ) 7.7 Hz), 2.22 (6H, t, J ) 7.7
Hz), 4.15 (6H, s), 4.40 (6H, s), 4.57 (4H, q, J ) 7.7 Hz), 4.79
(4H, q, J ) 7.7 Hz), 8.26 (2H, t, J ) 7.4 Hz), 8.37 (2H, d, J )
7.7 Hz), 9.58 (2H, d, J ) 7.1 Hz), 11.74 (2H, s), 12.25 (2H, s);
13C NMR (CDCl3) δ 11.7, 16.5, 17.7, 17.9, 18.0, 20.4, 20.7, 91.4,
95.7, 121.6, 122.0, 126.4, 127.0, 127.2, 127.9, 129.3, 133.3,
133.9, 134.5, 135.5, 136.2, 141.2, 141.8, 142.2; 13C NMR (TFA-
CDCl3) δ 13.0, 15.7, 17.4, 17.7, 21.1, 21.3, 94.9, 98.0, 125.5,
129.3, 129.7, 130.1, 131.3 (2), 133.2, 133.5, 136.4, 136.5, 137.3,
143.3, 145.1, 145.3; hr ms calcd for C46H47N5 669.3831, found
669.3819.
3,7,18,22-Tetraethyl-2,8,17,23-tetramethyl-27-carba-
benzo[l]sapphyrin (24). 24 was prepared by the foregoing
procedure from tetrapyrrole 11b (52 mg), diformylindene 2362
(16 mg), TFA (1 mL), and CH2Cl2 (99 mL). Following extrac-
tion, as above, and evaporation of the organic solvents, the
resulting blue residue was chromatographed over Grade III
alumina eluting with 5% methanol-chloroform and then on
a silica column eluting with 10% methanol-chloroform. The
product eluted as a bright teal-blue fraction. Recrystallization
from chloroform-hexanes afforded the carbasapphyrin 24‚HCl
as blue crystals (23 mg, 36%), mp >300 °C; UV-vis (1% DBU-
CHCl3; free base) λmax (log ꢀ) 377 (4.51), 470 (5.33), 596 (4.20),
645 (4.32), 710 (3.94), 793 nm (4.12); UV-vis (CHCl3; mono-
cation) λmax (log ꢀ) 374 (4.49), 476 (5.40), 496 (5.08), 613 (4.09),
669 (4.40), 708 (3.95), 788 nm (4.33); UV-vis (5% TFA-CHCl3;
dication) λmax (log ꢀ) 351 (4.60), 482 (5.55), 527 (4.22), 601
(3.98), 652 (4.18), 722 nm (4.43); 1H NMR (CDCl3; monocation)
δ -7.88 (1H, br s), -5.08 (2H, br s), -4.43 (2H, br s), 2.06
(6H, t, J ) 7.6 Hz), 2.12 (6H, t, J ) 7.6 Hz), 4.08 (6H, s), 4.13
(6H, s), 4.51 (4H, br q), 4.63 (4H, br q), 7.94-7.97 (2H, m),
9.33-9.37 (2H, m), 11.13 (2H, s), 11.32 (2H, s); 1H NMR (TFA-
CDCl3; dication) δ -3.75 (2H, br s), -0.56 (2H, br s), 0.67 (2H,
br s), 1.76 (6H, t, J ) 7.7 Hz), 1.89 (6H, t, J ) 7.7 Hz), 3.43
(6H, s), 3.66 (6H, s), 3.93 (4H, q, J ) 7.7 Hz), 4.12 (4H, q, J )
7.8 Hz), 8.70-8.74 (2H, m), 9.99-10.04 (2H, m), 10.37 (2H,
s), 11.05 (2H, s); 13C NMR (TFA-CHCl3) δ 11.8,13.9,16.9, 17.2,
20.3, 20.7, 30.6, 104.6, 109.2, 123.0, 123.1, 127.0, 129.5, 130.9,
131.6, 132.8, 133.2, 144.6, 144.7, 145.2, 148.9; hr ms calcd for
C41H45N4 593.3644, found 593.3645. Anal. Calcd for C41H44N4‚
HCl‚0.2CHCl3: C, 75.76; H, 6.98; N, 8.58. Found: C, 75.79;
H, 7.17; N, 8.58.
1
12.46 (1H, s); H NMR (TFA-CDCl3) δ -7.06 (2H, s), -4.31
(1H, s), -4.21 (1H, s), -2.67 (2H, s), 1.89-1.96 (6H, two
overlapping triplets), 2.06-2.11 (6H, two overlapping triplets),
3.85 (3H, s), 3.86 (3H, s), 4.04 (3H, s), 4.06 (3H, s), 4.30-4.36
(4H, two overlapping quartets), 4.50-4.57 (4H, two overlap-
ping quartets), 11.39 (1H, s), 11.40 (1H, s), 11.65 (1H, s), 11.99
(1H, s), 12.10 (1H, s), 12.85 (1H, s); hr ms calcd for C38H42N4O
570.3359, found 570.3365.
Azulisapphyrin 28. 28 was prepared as above from tet-
rapyrrole dicarboxylic acid 11b (50 mg), 1,3-azulenedicarbal-
dehyde64 (17 mg), TFA (1 mL) ,and dichloromethane (99 mL).
After the solvent was removed under reduced pressure the
resulting dark brown residue was chromatographed on silica
and the product eluted as an orange fraction with 15%
methanol-chloroform. Recrystallization from chloroform-
trace methanol-hexanes yielded the azulene derivative 28‚
2HCl as a dark blue powder (19 mg, 35%), mp >300 °C; UV-
vis (CHCl3) λmax (log ꢀ) 420 (4.94), 455 (4.78), 481 (4.80), 511
(4.86), 742 nm (4.41); UV-vis (1% TFA-CHCl3) λmax (log ꢀ)
416 (5.00), 449 (4.83), 478 (4.86), 505 (4.95), 736 nm (4.54);
UV-vis (5% TFA-CHCl3) λmax (log ꢀ) 413 (5.00), 449 (4.84),
475 (4.87), 504 (4.97), 734 nm (4.57); UV-vis (pyridine) λmax
(log ꢀ) 421 (4.90), 452 (4.79), 482 (4.82), 508 (4.83), 673 (sh,
4.00), 740 nm (4.41); UV-vis (1% DBU-CHCl3; free base) λmax
(log ꢀ) 415 (4.85), 457 (4.79), 490 (sh, 4.63), 525 (4.62), 609
(sh, 3.92), 704 (sh, 3.92), 781 nm (4.18); UV-vis (1% pyrroli-
dine-CHCl3) λmax (log ꢀ) 480 (5.09), 606 (4.14), 651 (4.21), 834
1
nm (4.08); H NMR (d5-pyridine-CDCl3, 20 °C) δ -3.25 (1H,
br s), -1.45 (1H, br s), -0.55 (1H, br s), 1.94-2.06 (12H, br
m), 3.83 (6H, s), 3.89 (6H, s), 4.28 (4H, br q), 4.40 (4H, br q),
8.30 (1H, t, J ) 8 Hz), 8.36-8.48 (2H, br m), 10.6 (2H, v br s),
1
10.66 (2H, br d), 11.1 (2H, v br s); H NMR (TFA-CDCl3, 50
°C) δ -4.8 (1H, br s), -3.4 (4H, br s), 1.95 (6H, t, J ) 7.4 Hz),
2.01 (6H, t, J ) 7.4 Hz), 3.88 (6H, br s), 3.98 (6H, br s), 4.18-
4.28 (4H, m), 4.37 (4H, q), 8.51 (1H, br), 8.63 (2H, br), 10.5
(2H, v br s), 10.55 (2H, br d), 11.1 (2H, v br s); 13C NMR (d5-
pyridine-CDCl3) δ 15.2,29.8, 35.3, 36.9, 101.6, 104.0, 119.9,
122.1, 126.5, 127.5, 128.6, 131.9, 132.7, 136.3, 136.7, 139.1,
140.5, 145.8; fab hr ms calcd for C42H45N4 605.3644, found
605.3646.
Acknowledgment. This material is based upon
work supported by the National Science Foundation
under Grant No. CHE-0134472, and the Petroleum
Research Fund, administered by the American Chemi-
cal Society.
3,7,18,22-Tetraethyl-12-formyl-2,8,17,23-tetramethyl-
27-carbasapphyrin (26). Following the procedure described
above, the carbasapphyrin was prepared from tetrapyrrole
dicarboxylic acid 11b (25 mg) and 1,3,4-triformylcyclopenta-
JO040239O
(63) Hafner, K.; Vo¨pel, K. H.; Ploss, G.; Ko¨nig, C. Liebigs Ann. Chem.
1963, 661, 52.
(64) Hafner, K.; Bernhard, C. Liebigs Ann. Chem. 1959, 625, 108.
(62) Arnold, Z. Collect. Czech. Chem. Commun. 1965, 30, 2783.
8850 J. Org. Chem., Vol. 69, No. 25, 2004