Adj-diazuliporphyrins, a new family of dicarbaporphyrinoids with unprecedented mesoionic characteristics

Article abstract of DOI:10.1021/ol802406f

A diazulenylmethane dialdehyde reacted with dipyrrylmethanes in the presence of HCl or HBr, followed by oxidation with FeCl₃, to give aromatic adj-diazuliporphyrins. The free base structures must exist as mesoionic species, although these porphyrinoids were isolated as salts of the monoprotonated macrocycles. Reaction with Pd(OAc)₂ gave an unprecedented zwitterionic palladium(II) complex that was characterized by X-ray crystallography.

Full text of DOI:10.1021/ol802406f

ORGANIC
LETTERS
2
009
Vol. 11, No. 1
01-104
adj-Diazuliporphyrins, a New Family of
Dicarbaporphyrinoids with
Unprecedented Mesoionic
Characteristics
Zhenjun Zhang, Gregory M. Ferrence, and Timothy D. Lash*
1
†
Department of Chemistry, Illinois State UniVersity, Normal, Illinois 61790-4160
tdlash@ilstu.edu
Received October 18, 2008
ABSTRACT
A diazulenylmethane dialdehyde reacted with dipyrrylmethanes in the presence of HCl or HBr, followed by oxidation with FeCl
aromatic adj-diazuliporphyrins. The free base structures must exist as mesoionic species, although these porphyrinoids were isolated as salts
3
, to give
of the monoprotonated macrocycles. Reaction with Pd(OAc)
by X-ray crystallography.
2
gave an unprecedented zwitterionic palladium(II) complex that was characterized
1
N-Confused porphyrins (NCPs; 1) and related carbapor-
2
phyrinoid systems such as the azuliporphyrins 2 have
attracted considerable interest due to their unusual reactivity
3
and spectroscopic properties, as well as their potential utility
4
in medicinal applications. These analogues also provide
5
insights into the nature of porphyrinoid aromaticity and have
been shown to generate organometallic derivatives under
6
,7
mild conditions. Two examples of doubly N-confused
porphyrins (N CPs) have been reported that introduce a
second carbon atom into the porphyrinoid core, but these
retain the ability to form organometallic derivatives with
2
8
metals in higher oxidation states such as Ag(III). In our
previous investigations, several examples of dicarbaporphy-
(
3) (a) Lash, T. D. Synlett 2000, 279–295. (b) Lash, T. D. Eur. J. Org.
†
Conjugated Macrocycles Related to the Porphyrins. 49. For part 48,
Chem. 2007, 5461–5481.
see: Lash, T. D.; Young, A. M.; Von Ruden, A. L.; Ferrence, G. M. Chem.
Commun. 2008, DOI: 10.1039/b816057k.
(4) Morganthaler, J. B.; Peters, S. J.; Cede n˜ o, D. L.; Constantino, M. H.;
Edwards, K. A.; Kamowski, E. M.; Passini, J. C.; Butkus, B. E.; Young,
A. M.; Lash, T. D.; Jones, M. A. Bioorg. Med. Chem. 2008, 16, 7033–
7038.
(1) (a) Latos-Grazynski, L. Core-Modified Heteroanalogues of Porphy-
rins and Metalloporphyrins. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 2,
pp 361-416. (b) Srinivasan, A.; Furuta, H. Acc. Chem. Res. 2005, 38, 10–
(5) Aihara, J.-i. J. Phys. Chem. A 2008, 112, 5305–5311.
(6) Harvey, J. D.; Ziegler, C. J. Coord. Chem. ReV. 2003, 247, 1–19.
(7) (a) Lash, T. D.; Colby, D. A.; Graham, S. R.; Ferrence, G. M.;
Szczepura, L. F. Inorg. Chem. 2003, 42, 7326–7338. (b) Lash, T. D.;
Rasmussen, J. M.; Bergman, K. M.; Colby, D. A. Org. Lett. 2004, 6, 549–
552.
2
0.
(
2) (a) Lash, T. D.; Chaney, S. T. Angew. Chem., Int. Ed. Engl. 1997,
3
5
6, 839–840. (b) Colby, D. A.; Lash, T. D. Chem.sEur. J. 2002, 8, 5397–
402.
10.1021/ol802406f CCC: $40.75
Published on Web 12/02/2008
 2009 American Chemical Society

9
a
rinoids with either two indene subunits or an azulene and
diazuliporphyrins are the first examples of mesoionic por-
phyrinoid systems.
9b,c
indene moiety have been described, and these results have
Dialdehydes 3 are easily prepared in virtually quantitative
yields by reacting the corresponding azulene monoalde-
1
1,12
11
hydes
with paraformaldehyde in acetic acid. In prin-
Scheme 1
ciple, dialdehyde structures of this type can be used in
13
MacDonald “2 + 2” condensations with dipyrrylmethanes
to form porphyrinoid macrocycles (Scheme 1). Initially,
reactions of 3a and 3b with 4a were attempted in
TFA-CH Cl , but no porphyrinoid products could be
4
2
2
isolated. However, when these condensations were conducted
in acetic acid with catalytic HCl or HBr, followed by
1
4
oxidation with FeCl
3
,
the novel adj-diazuliporphyrins 5
were generated. Although poor results were obtained for
reactions using 3a, excellent yields (43-56%) of diazuli-
porphyrins 5a·HCl or 5a·HBr could be isolated using bis-
tert-butyl dialdehyde 3b. Prior to the oxidation step, a
diazuliphlorin 6a or a related dihydroporphyrinoid would be
produced, and it was not immediately clear how this
framework could allow conjugation between the two azulene
units. However, following the oxidation step and treatment
2
+
with HCl or HBr, the fully conjugated dications 5H
2
were
indeed generated, and after column chromatography on silica
the monoprotonated hydrochloride or hydrobromide salts
could be isolated. A related diester 5b·HBr was also
synthesized from 3b and 4b. The UV-vis spectra of the
nondescript gray-purple solutions of 5·HCl and 5·HBr were
similar, showing broad absorptions at 379 and 566 nm
(Figure 1). Addition of TFA produced violet solutions of
Figure 1
monocation; green line), 1% TFA-CHCl
and 1% DBU-CHCl (mesoionic free base; red line) showing the
formation of three different species.
.
UV-vis absorption spectra for 5b·HBr in CHCl
3
(
3
(dication; purple line),
3
2
+
the dications 5H
2
with a strong absorption at 571 nm.
However, in 1% DBU-chloroform, green solutions of the
free base species 5 were generated. The neutral system can
provided further insights into the nature of porphyrinoid
aromaticity. In this paper, the synthesis of a remarkable new
family of dicarbaporphyrinoids with two adjacent azulene
(10) Two examples of conjugated macrocycles with alternating azulene
and furan or thiophene subunits have been reported. See: (a) Sprutta, N.;
1
0
subunits is described. To the best of our knowledge, these
Swiderska, M.; Latos-Grazynski, L. J. Am. Chem. Soc. 2005, 127, 13108–
1
3109. (b) Sprutta, N.; Siczek, M.; Latos-Grazynski, L.; Pawlicki, M.;
Szterenberg, L.; Lis, T. J. Org. Chem. 2007, 72, 9501–9509.
(
8) (a) Furuta, H.; Maeda, H.; Osuka, A. J. Am. Chem. Soc. 2000, 122,
(11) Ito, S.; Morita, N.; Asao, T. Bull. Chem. Soc. Jpn. 1999, 72, 2543–
8
1
03–807. (b) Maeda, H.; Osuka, A.; Furuta, H. J. Am. Chem. Soc. 2003,
2548.
25, 15690–15691.
(12) Lash, T. D.; El-Beck, J. A.; Ferrence, G. M. J. Org. Chem. 2007,
72, 8402–8415
(
9) (a) Lash, T. D.; Romanic, J. L.; Hayes, M. J.; Spence, J. D. Chem.
.
Commun. 1999, 819–820. (b) Graham, S. R.; Colby, D. A.; Lash, T. D.
Angew. Chem., Int. Ed. 2002, 41, 1371–1374. (c) Lash, T. D.; Colby, D. A.;
Idate, A. S.; Davis, R. N. J. Am. Chem. Soc. 2007, 129, 13800–13801.
(13) Lash, T. D. Chem.sEur. J. 1996, 2, 1197–1200.
(14) Lash, T. D.; Richter, D. T.; Shiner, C. M. J. Org. Chem. 1999, 64,
7973–7982.
102
Org. Lett., Vol. 11, No. 1, 2009

only be written as a series of dipolar resonance contributors
and for this reason may be considered to be a very unusual
example of a mesoionic system. The isolated monoprotonated
Figure 3. ORTEP-3 drawing (50% probability level, hydrogen
atoms drawn arbitrarily small, one of four crystallographically
independent molecules, bromide counterion not shown) of diazu-
liporphyrin hydrobromide 5b·HBr.
Figure 2
. Partial 400 MHz proton NMR spectra of 5a·HBr showing
details of the upfield and downfield regions. (A) 5a·HBr in CDCl
3
.
2
+
(
B) Dication 5H
2
3
in TFA-CDCl . The broad upfield resonance
for the internal CHs shifts upfield by nearly 1 ppm on addition of
TFA.
Scheme 2
species must also take on unconventional tropylium type
+
+
2+
contributors such as 5H and 5′H , and the dications 5H
are also best represented in this way. Hydrochloride salt
a·HCl was somewhat insoluble in organic solvents, but
2
5
proton NMR data was obtainable in CDCl
3
and these showed
+
that 5aH has a significant diatropic ring current as the
internal 21,22-CH resonance shows up as a broad upfield
singlet at 0.9 ppm. Better resolved spectra could be obtained
for the more soluble hydrobromide salts 5a·HBr and diester
5
3
b·HBr. The 21,22-CH resonance for 5a·HBr in CDCl was
shifted upfield to -0.05 ppm, while the meso-protons gave
rise to three singlets at 7.3 (1H), 8.1 (2H), and 10.6 ppm
(
1H) (Figure 2). Apart from confirming that this highly
crystal refined to only a relatively high R value, although
modified porphyrin analogue system retains a high degree
of diatropic character, the proton NMR spectra confirm that
the macrocycle possesses the plane of symmetry that is
expected for the fully delocalized aromatic species. This
symmetry is also evident in the carbon-13 NMR spectra for
prior to any refinement, all of the non-hydrogen atoms
present in the four crystallographically independent
+
[C50H N O
53 2 4
] residues were immediately identified from the
SHELXS-97 solution. As all four diazuliporphyrins show
essentially the same macrocyclic conformation, the crystal
structure adequately proves the non-hydrogen content of the
main residues.
5
a and 5b. Addition of a drop of TFA to the NMR tube
2
+
gave the dications 5H
2
, and these also showed diatropic
ring currents with the 21,22-CH resonance at 0.8 ppm. The
NH resonance could also be identified near 2.5 ppm while
the external meso-protons shifted further downfield giving
resonances at 8.4 (1H), 9.2 (2H), and 10.7 ppm (1H). When
The formation of the palladium(II) complex of 5a was also
investigated (Scheme 2). The best results were obtained when
5a·HBr was heated with a slight excess of Pd(OAc) in
2
acetonitrile, and following chromatography on silica gel, the
polar metallo-derivative 8 was isolated in 26% yield. In
addition to forming two carbon-palladium bonds under mild
conditions, this species must exist as an unprecedented
mesoionic structure in order to accommodate the palla-
dium(II) cation. Again, this system must possess extensive
tropylium character, as represented in canonical forms 8 and
8′. Proton NMR data for 8 could only be obtained in DMSO-
3
TFA-d was added to the NMR solution of 5a·HBr in CDCl ,
slow exchange of the 15-CH resonance occurred over several
hours at room temperature and this result indicates that a
C-protonated dication 7, or a related tricationic species, must
2+
be present in equilibrium with 5H
2
. X-ray crystallographic
data were also obtained for 5b·HBr, and this confirms that
the porphyrinoid macrocycle contains two azulene and two
pyrrole moieties. However, the quality of these results were
only sufficient to confirm the connectivity and conformation
of the carbon framework and could not identify the internal
protons or the location of the bromide ion (Figure 3; see
also the Supporting Information). The weakly diffracting
6
d (Figure 4), but in this solvent the complex displayed a
similar diatropic ring current to the parent system and the
meso-protons gave rise to three downfield resonances at 7.9
(1H, s), 8.8 (2H, s), and 10.0 ppm (1H, s). The symmetry of
this system is evident in the proton and carbon-13 NMR
Org. Lett., Vol. 11, No. 1, 2009
103

Figure 4
. Partial 400 MHz proton NMR spectrum of 8 in DMSO-
d
6
showing details of the aromatic region. The downfield shifts
indicate that the palladium complex retains significant diatropic
character.
Figure 5. ORTEP-3 drawing (50% probability level, hydrogen
atoms drawn arbitrarily small, one of two crystallographically
independent molecules) of palladium complex 8. Selected bond
lengths (Å): Pd1-C21 1.960(4), Pd1-C22 1.969(5), Pd1-N24
2.058(4), Pd1-N23 2.075(4), C1-C2 1.451(6), C2-C3 1.427(7),
C3-C4 1.445(6), C4-C21 1.432(6), C21-C1 1.438(7), C4-C5
spectra for 8, and FAB MS confirmed the presence of a
palladium atom. The structure of 8 was confirmed by single-
crystal X-ray diffraction analysis of a partial chloroform
solvate. Bond parameters for only one of the two crystallo-
graphically independent molecules are shown in Figure 5;
however, there are no significant differences in the values
1
.395(6), C5-C6 1.398(6), C6-C7 1.434(7), C7-C8 1.452(6),
C8-C9 1.445(6), C9-C22 1.425(6), C22-C6 1.438(6), C9-C10
1
.415(6), C10-C11 1.360(6), C11-C12 1.470(6), C12-C13
.331(7), C13-C14 1.471(6), C14-C15 1.380(7), C15-C16
1
1.388(7), C16-C17 1.457(7), C17-C18 1.364(7), C18-C19
1
.456(7), C19-C20 1.373(7), C20-C1 1.415(7), C11-N23 1.386(6),
obtained for these two molecules. The data for 8·0.6CHCl
3
N23-C14 1.365(6), C16-N24 1.371(6), N24-C19 1.385(6).
confirms a macrocycle containing two azulene moieties, each
coordinated along with the two pyrrole moieties to a central
palladium(II) ion. The distances (0.118 Å rms) at which
Selected bond angles (deg): C21-Pd1-C22 89.1(2), C22-Pd1-N23
9
0.7(2), N23-Pd1-N24 88.9(2), N24-Pd1-C21 91.4(2).
4
skeletal atoms lie from the plane defined by PdL classify
the porphyrin skeleton as slightly saddled, although this is
slightly less than the value (0.293 Å rms) observed for a
Acknowledgment. This material is based upon work
7a
supported by the National Science Foundation under Grant
Nos. CHE-0616555 (to T.D.L.) and CHE-0348158 (to
G.M.F.) and the Petroleum Research Fund, administered by
the American Chemical Society. We also thank Youngstown
State University’s Matthias Zeller for X-ray data collection.
related palladium(II) monoazuliporphyrin complex. As the
framework bond distances are consistent with a somewhat
localized π-bonding model, the planarity must primarily be
dictated by constraints of metal atom binding, namely the
Pd(II) size, square-planar coordination, and optimal Pd-N
and Pd-C bond lengths.
In conclusion, unusual mesoionic diazuliporphyrins have
been synthesized and the spectroscopic data demonstrate that
this system possesses tropylium and porphyrin-like aromatic
characteristics. In addition, the formation and structural
characterization of a stable palladium(II) organometallic
derivative has been accomplished.
Supporting Information Available: Experimental pro-
1
13
cedures, selected UV-vis, H NMR and C NMR spectra,
and crystallographic data for 5b·HBr and 8 are provided. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL802406F
104
Org. Lett., Vol. 11, No. 1, 2009