Preparation of azulene-derived fulvenedialdehydes and their application to the synthesis of stable adj -dicarbaporphyrinoids

Article abstract of DOI:10.1021/jo2026977

A "2 + 2" strategy for synthesizing adj-dicarbaporphyrinoid systems has been developed. In a model study, an azulenylmethylpyrrole dialdehyde was condensed with a dipyrrylmethane in the presence of HCl, followed by oxidation with ferric chloride, to give

Full text of DOI:10.1021/jo2026977

Article
pubs.acs.org/joc
Preparation of Azulene-Derived Fulvenedialdehydes and Their
Application to the Synthesis of Stable adj-Dicarbaporphyrinoids†
Timothy D. Lash,* Aaron D. Lammer, Aparna S. Idate, Denise A. Colby, and Kristen White
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, United States
S
* Supporting Information
ABSTRACT: A “2 + 2” strategy for synthesizing adj-dicar-
baporphyrinoid systems has been developed. In a model study,
an azulenylmethylpyrrole dialdehyde was condensed with a
dipyrrylmethane in the presence of HCl, followed by oxidation
with ferric chloride, to give a modest yield of an azuli-
porphyrin. Fulvene aldehydes were prepared by reacting an
indene-derived enamine with azulene aldehydes in the
presence of Bu2BOTf, and azulene dialdehydes similarly
reacted to give fulvene dialdehydes. The dialdehydes were
condensed with dipyrrylmethanes in TFA/dichloromethane to afford good to excellent yields of dicarbaporphyrinoids with
adjacent indene and azulene subunits. These 22-carbaazuliporphyrins exhibited significant diatropic character, and this property
was magnified upon protonation. These characteristics are attributed to tropylium-containing resonance contributors that possess
18π electron delocalization pathways. Protonation studies demonstrated that C-protonation readily occurred at the interior
indene carbon, but deuterium exchange also occurred at the internal azulene CH as well as at the meso-positions with TFA-d.
Reaction of a carbaazuliporphyrin with silver(I) acetate in methanol or ethanol solutions also gave unusual nonaromatic dialkoxy
derivatives.
also undergo an oxidative metalation reaction with copper-
(II) salts to give nonaromatic coordination complexes 8
(Scheme 1).21 Furthermore, azuliporphyrins undergo oxida-
tive ring contractions with peroxides under alkaline conditions
(e.g., with KOH-t-BuOOH) to afford benzocarbaporphyrins
(Scheme 1).23
INTRODUCTION
■
Carbaporphyrinoid systems, porphyrin analogues where one or
more of the internal nitrogens are replaced by carbons,
continue to attract a considerable amount of attention.1−3
This is due in part to the unique properties exhibited by these
macrocycles, which provide organized binding cavities that can
afford unusual organometallic derivatives. Most of the research
in this area has focused on monocarbaporphyrinoids, where
only one carbon is present within the macrocyclic cavity. This
work includes investigations on the so-called N-confused
porphyrins 1,4 benzocarbaporphyrins 2,5 azuliporphyrins 3,6,7
tropiporphyrins,8 carbachlorins,9 benziporphyrins,10−12 oxy-
benziporphyrins,11,12 naphthiporphyrins,13 O- and S-confused
heteroporphyrins,14 neo-confused porphyrins,15 pyrazolopor-
phyrins,16 and N-confused pyriporphyrins.17 Most of these
macrocyclic platforms have been shown to form stable organo-
metallic complexes,18,19 and unusual oxidation reactions have
also been reported.20,21 For instance, benzocarbaporphyrins 2
react with silver(I) acetate to give silver(III) derivatives 4
(Scheme 1),18 and gold(III) complexes have also been report-
ed.18b However, reaction of porphyrinoids 2 with ferric chloride
and alcohols gave rise to regioselective oxidations that afforded
unusual carbaporphyrin ketals 5 which exhibit strong absorp-
tions in the far red (Scheme 1).20 These polar oxidation produ-
cts are promising photosensitizing agents and have been shown
to be active agents in the treatment of leishmaniasis.22 Azulipor-
phyrins 3 behave somewhat differently, acting as dianionic
ligands and favoring the formation of nickel(II), palladium(II),
and platinum(II) derivatives 6.19 Tetraarylazuliporphyrins 7
Investigations into dicarbaporphyrinoid systems have devel-
oped comparatively slowly. The first example of a dicarbapor-
phyrin 9 was obtained by reacting indane dialdehyde 10 with
3,4-diethylpyrrole in the presence of HBr, followed by
oxidation with ferric chloride (Scheme 2).24 This system is
highly diatropic, and the proton NMR spectrum for 9 in CDCl3
gave rise to upfield singlets for the internal CHs and NHs at
−5.68 and −4.82 ppm, respectively, while the external meso-
protons afforded a 4H singlet at 9.79 ppm.24 Addition of TFA
to solutions of 9 gave the related C-protonated cation 9H+ and
this retained diatropic character, showing the internal
methylene unit as a 2H singlet at −4.34 ppm, while the
remaining indene CH and the NHs gave resonances at −3.30
and −0.95 ppm, respectively.24 Unfortunately, dicarbaporphyr-
in 9 proved to be somewhat unstable, and this has limited
further investigations. Further examples of opp-dicarbaporphyr-
inoids have been reported, including the 23-carbaazuliporphyr-
in 1125 and the resorcinol-derived species 1226 (Scheme 3).
Carbaazuliporphyrin 11, which was also rather unstable, was
prepared by treating azulitripyrrane 13 with TFA, followed by a
Received: December 31, 2011
Published: January 30, 2012
© 2012 American Chemical Society
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Scheme 1
Scheme 2
Scheme 3
appeared as 1H singlets at 0.52, 1.25, and 1.99 ppm.25 These
results suggest that this system has comparable diatropic
character to azuliporphyrins 3. Addition of TFA to solutions of
2+
11 afforded the related dication 11H2 where C-protonation
had again occurred on the indene unit.25 24-Carbaoxybenzi-
porphyrins 12, which were also prepared by a “3 + 1” approach
from tripyrrane analogues 15 and dialdehyde 14 (Scheme 3),
were poorly soluble in most organic solvents, but in DMSO-d6
this system exhibited a pronounced diamagnetic ring current
and the proton NMR spectra showed the internal CH protons
near −5 ppm.26 Examples of cis-N-confused porphyrins 16a27
and trans-N-confused porphyrins 16b28 have also been
reported, although only the latter shows a significant degree
of diatropicity.29
“3 + 1” condensation with indene dialdehyde 14 (Scheme 3).25
The proton NMR spectrum of 11 showed a degree of
diatropicity and the internal indene, azulene and NH protons
Until recently, very little work had been carried out on the
synthesis of dicarbaporphyrinoid systems where the subunits
possessing the internal CHs are adjacent to one another (i.e.,
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adj-dicarbaporphyrinoids) rather than opposite. We speculated
that structures of this type might be accessible using fulvene
dialdehydes 17 as the key intermediates (Scheme 4). Acid-
Scheme 6
Scheme 4
catalyzed MacDonald-type “2 + 2” condensation30 of 17 with
dipyrrylmethanes 18 would be expected to afford novel
dicarbaporphyrinoids 19 (Scheme 4). However, fulvenes
dialdehydes of this type had not been reported previously,
and a synthetic strategy for the preparation of these crucial
intermediates had to be developed. In this paper, the synthesis
of azulene-derived fulvene mono- and dialdehydes are descri-
bed, and syntheses of 22-carbaazuliporphyrins are reported.31,32
Although this new class of adj-dicarbaporphyrinoids failed to
generate organometallic derivatives, unusual oxidation reactions
were observed.
RESULTS AND DISCUSSION
■
In most cases, carbaporphyrinoid systems have been prepared
by a “3 + 1” variant on the MacDonald condensation,33 and
little use of the “2 + 2” methodology has been made.34,35 For
instance, azuliporphyrins 3 are readily prepared by reacting
azulene dialdehydes 20 with tripyrranes 21 in the presence of
TFA, followed by oxidation with DDQ or ferric chloride
(Scheme 5).6 As the use of the “2 + 2” strategy was crucial to
Scheme 5
POCl3−DMF, followed by hydrolysis with aqueous sodium
acetate solution, afforded the monoaldehyde 25 in 66% yield,
but the azulene moiety for this structure was also prone to
reduction with hydrogen and 10% Pd/C. In order to overcome
these problems, the related tert-butyl ester 24b was prepared in
56% yield by reacting azulene with acetoxymethylpyrrole 23b in
refluxing acetic acid-2-propanol. Treatment of 24b with TFA
smoothly cleaved the tert-butyl ester to afford 25 and
subsequent Vilsmeier formylation with POCl3-DMF afforded
the required dialdehyde 22 in 61% yield. The “2 + 2”
condensation of 22 with dipyrrylmethane 18a36 was inves-
tigated using a variety of acid catalysts, including TFA, p-
toluenesulfonic acid, HCl, and HI (Scheme 6). An oxidation
step is also necessary to afford the fully conjugated
azuliporphyrin system. The best results were obtained when
18a was first treated with TFA and then diluted with acetic
the development of synthetic routes to adj-dicarbaporphyrinoid
systems, we elected to carry out a model study to assess the
viability of preparing azuliporphyrins by this approach. This
required the preparation of an azulenylmethylpyrrole dialde-
hyde 22 that could be used in a MacDonald-type condensation
(Scheme 6). The reaction of azulene with acetoxymethylpyrrole
23a in the presence of acetic acid was somewhat solvent
dependent. In refluxing acetic acid−ethyl acetate, the
monosubstituted azulenes 24a was isolated in 18% yield. In
2-pentanol, the yield was raised to 24%, but the best results
were obtained in refluxing 2-propanol containing 10% acetic
acid and 24a could be isolated in 50% yield together with a
related tripyrrane analogue (dibenzyl ester related to structure
13). However, attempts to deprotect benzyl ester 24a with
hydrogen over 10% palladium−charcoal led instead to
hydrogenation of the azulene unit. Reaction of 24a with
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acid. The dialdehyde was then added, followed by a few drops
of concd HCl, and the mixture was stirred under nitrogen for
16 h. The product was extracted with chloroform and oxidized
by shaking the solution with a 0.1% aqueous solution of ferric
chloride. Inferior results were obtained using DDQ as the
oxidant. Under optimized conditions, following purification by
column chromatography and recrystallization from chloroform-
hexanes, azuliporphyrin 27 was isolated in 13% yield.
This result demonstrates that the “2 + 2” route is a viable
method for preparing carbaporphyrinoid systems but in the
case of azuliporphyrins the “3 + 1” approach is a far superior
methodology.6 However, unlike structures prepared by the
“3 + 1” approach, azuliporphyrin 27 is asymmetrically substi-
tuted, and this product had improved solubility in organic
solvents. The UV−vis spectrum for 27 is typical of azuli-
porphyrins, showing four moderately intense bands at 355, 397,
445, and 472 nm and a broad absorption at higher wavelengths.
The improved solubility of 27 allowed relatively high quality
proton NMR spectra to be obtained, although the internal CH
and NH resonances could not be identified. The meso-protons
gave rise to four 1H singlets at 8.04, 8.05, 8.90, and 8.92 ppm,
indicating that the macrocycle has significant diatropic
character. This is commonly attributed to dipolar resonance
contributors such as 27′ (Scheme 6) that possess 18π electron
delocalization pathways. Addition of TFA leads to the
Scheme 8
to direct substitution onto the cyclopentadiene moiety and
thereby facilitate the formation of the desired fulvene
dialdehyde 31. Resonance contributors such as 28′ and 28″
suggest that electrophilic substitution at the required positions
may be favorable (Scheme 9), and with this in mind, the
Scheme 9
Vilsmeier formylation of 28 was attempted. Unfortunately,
fulvene 28 is not very stable, and poor yields of the substitution
products were isolated. However, a fraction corresponding
to the monoaldehyde 32 was isolated together with a small
amount of a dialdehyde tentatively identified as 33 (Scheme 7).
These results provide proof of principle that the azulene moiety
can direct substitution onto the cyclopentadiene ring. However,
substitution onto the cyclopentadiene ring does not take place
at the required position, and the instability of these products
prevented further investigations. There are four open positions
on the cyclopentadiene unit, and this factor facilitates the
undesired regioselectivity for the formylation reaction. Clearly,
if some of these sites are blocked it may be possible to
introduce the formyl group at the desired position. Indene was
reacted with azulene aldehyde 29a and potassium hydroxide
in refluxing methanol to give fulvene 34a in 78% yield
(Scheme 10). In this system, only two sites are open on the
2+
formation of a related dication 27H2 that shows a greatly
enhanced diatropic ring current. In the proton NMR spectrum,
the meso-protons are now observed at 9.47, 9.48. 10.33, and
10.35 ppm while the internal CH and NH resonances can be
observed at −2.85, −1.87, −0.16, and −0.15 ppm, respectively.
These results are similar to those previously reported for more
symmetrically substituted azuliporphyrins, albeit with an
increased number of proton resonances. The improved
diatropicity of 27H22+ is attributed to the increased favorability
2+
of canonical forms such as 27′H2 that provide beneficial
charge delocalization, whereas 27′ is less favorable due to the
requirement for charge separation.
In order to apply the “2 + 2” methodology to the synthesis of
adj-dicarbaporphyrinoids, suitably substituted fulvene dialde-
hydes were required. The preparation of a fulvene derivative of
azulene 28 was reported over 50 years ago by reacting 1-
azulenecarbaldehyde (29) with cyclopentadiene under basic
conditions (Scheme 7).37 Azulene favors electrophilic sub-
Scheme 10
Scheme 7
stitution at the 1- and 3-positions due to the formation of an
intermediary tropylium cation 30 (Scheme 8), and we
speculated that the azulene unit in fulvene 28 might be able
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cyclopentadiene unit, and this limits the possible outcomes for
electrophilic substitution reactions. In addition, unlike fulvene
28, 34a is a very stable compound and crystallizes as lustrous
green crystals. A related fulvene 34b was also easily prepared
from 6-tert-butylazulene-1-carbaldehyde (29b) and indene, and
this derivative was equally robust and easy to handle. In
addition, azulene dialdehyde 20a reacted with indene and KOH
in refluxing ethanol to give difulvene 35 in 81% yield, and this
also proved to be a stable compound. Therefore indene-derived
fulvenes exhibit considerably improved characteristics for
synthetic investigations. Fulvene 34a was reacted with
POCl3−DMF and gave monoaldehyde 36 as the major
product, although a low yield of the desired dialdehyde 37a
was observed (Scheme 10). In small-scale reactions, yields of
37a as high as 27% were noted, but these results were poorly
reproducible and this approach did not provide a practical route
to this intermediate.
solution, gave fulvene monoaldehyde 39a in 75% yield. The
related tert-butyl-substituted fulvene was similarly obtained by
reacting 38 with 29b in the presence of Bu2BOTf. It had been
our expectation that the second aldehyde group could be
installed onto the azulene subunit by carrying out a Vilsmeier
formylation reaction, as this had been the preferential site for
electrophilic substitution in fulvene 34, but all attempts to carry
out this transformation failed to give fulvene dialdehyde 37a.
Therefore, an alternative method for introducing the second
aldehyde unit was needed. Halogenated azulene aldehydes
29c−f were prepared in two steps from the corresponding
azulenes (Scheme 12). Reaction of azulene with one equiv of
Scheme 12
The formylation of fulvene 34 occurred preferentially on the
azulene moiety and further substitution at the other terminus
for this system was not favored. With this in mind, an
alternative synthesis of fulvenes was developed that directly
introduces the formyl group on the indene subunit. Enamine
38 is easily prepared by reacting indene with DMF dimethyl
acetal in refluxing toluene (Scheme 11).38 In principle, this
Scheme 11
N-chlorosuccinimide in dichloromethane gave 1-chloroazulene
and the crude product was directly formylated with POCl3−
DMF to give 3-chloroazulene-1-carbaldehyde (29c) in 69%
yield. Similarly, azulene reacted with N-iodosuccinimide to give
1-iodoazulene and this was directly formylated with POCl3−
DMF to afford aldehyde 29e in 83% yield. The related tert-
butyl iodoaldehyde 29f was prepared similarly from 6-tert-
butylazulene. The best results for bromoazulene aldehyde 29d
were obtained by reversing the order of the two steps. Reaction
of azulene with POCl3−DMF produces 1-azulenecarbaldehyde
and subsequent treatment with N-bromosuccinimde in
dichloromethane gave 29d in 48% yield. The halogenated
azulenes were reacted with 38 and Bu2BOTf in dichloro-
methane, followed by hydrolysis with an aqueous sodium
acetate solution. Chloro- and bromoazulene aldehydes 29c and
29d afforded the corresponding fulvenes 39c and 39d in 59%
and 41% yields, respectively. However, reaction of iodoazulenes
29e and 29f under these conditions afforded a mixture of the
desired iodofulvenes together with the dehalogenated species
39a or 39b. The results varied somewhat from one experiment
to another but significant loss of iodine was noted in most of
these experiments. Fortunately, it was possible to carry out a
selective iodination reaction following fulvene formation.
Hence, fulvenes 39a and 39b reacted with N-iodosuccinimide
to give good yields of the iodo derivatives 39e and 39f. The
availability of halogenated fulvenes allowed us to consider the
introduction of the second formyl moiety by metal−halogen
exchange, followed by reaction with DMF. Unfortunately, this
approach also failed to give the desired dialdehydes. Aldehydes
39c−f were protected as the corresponding dimethyl acetals 41
with methanol and a catalytic quantity of p-toluenesulfonic acid,
and metal−halogen exchange was then attempted with n-
butyllithium or tert-butyllithium in anhydrous ether or THF.
No reaction was observed under any of the conditions that
were investigated. Magnesium ate complexes have been used to
enamine can be used to direct attack onto an aromatic aldehyde
while simultaneously introducing a formyl moiety at the desired
position on the indene. The reaction of 38 with 29a was
attempted with a number of Lewis acid catalysts including
AlCl3, SnCl4, TiCl4, (C5H5)2TiCl2, (C5H5)2ZrCl2, and Yb-
(OTf)3, but only TiCl4 gave even low yields of the expected
fulvene 39a. However, di-n-butylboron triflate was subsequently
found to be a superior catalyst for this reaction. Reaction of
azulene aldehyde 29a with indene enamine 38 in the presence
of 1 equiv of Bu2BOTf, followed by hydrolysis of the
intermediary imine salt 40 with an aqueous sodium acetate
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carry out metal−halogen exchange reactions,39 and have been
reported to give good results for metal−halogen exchange using
iodoazulenes,40 but treatment of 41c or 41d with n-Bu3MgLi
also gave poor results. Cyanovinyl substituents have been
widely used as protective groups for pyrrole aldehydes41 and
the utility of this protective unit for fulvene derivatives was also
briefly considered. Knoevenagel reaction of 1-azulenecarbalde-
hyde with ethyl cyanoacetate and piperidine in refluxing
ethanol afforded the corresponding cyanovinylazulene 42 in
97% yield (Scheme 13). Subsequent Vilsmeier formylation with
Scheme 14
Scheme 13
POCl3-DMF gave the related aldehyde 43 in 88% yield.
Reaction of 43 with enamine 38 and Bu2BOTf, followed by
hydrolysis with aqueous sodium acetate solution, then gave
fulvene aldehyde 39g in 81% yield (Scheme 11). Unfortunately,
deprotection of the cyanovinyl group requires strongly basic
reaction conditions, typically refluxing sodium hydroxide
solutions, and a procedure could not be found that could
remove the protective unit without causing complete
decomposition of the starting material.
already fully conjugated, condensation with dipyrrylmethanes
18 generates dicarbaporphyrinoids 44 directly.
adj-Dicarbaporphyrinoids proved to be very stable in
contrast to opp-dicarbaporphyrinoids such as the isomeric
system 11. In addition, the UV−vis spectra for 44a−d closely
resembled the spectra for azuliporphyrins 3 and 27. For
instance, the UV−vis spectrum for 44b gave rise to four
peaks at 368, 399, 470, and 494 nm, and broad absorptions
were also noted between 500 and 800 nm (Figure 1). These
Following from these investigations, attempts were made to
prepare fulvene dialdehydes 37 directly from azulene
dialdehydes 20 (Scheme 14). Hence, 1,3-azulenedicarbalde-
hyde (20a) was reacted with 1 equiv of indene enamine 38 and
Bu2BOTf to give the required dialdehyde 37a. It was necessary
to purify 37a using column chromatography on silica gel, but
this compound showed poor stability under these conditions,
and the best results were obtained when the purification was
carried out as rapidly as possible. Nevertheless, 37a could be
isolated in up to 53% yield. 6-tert-Butylazulene dialdehyde 20b
was also reacted with 38 and Bu2BOTf to give the related
fulvene dialdehyde 37b. This product was more robust, did not
appear to degrade during column chromatography, and was
isolated in 34% yield. Dialdehyde 37a was reacted with
dipyrrylmethane dicarboxylic acid 18a in TFA−dichloro-
methane, and following extraction, column chromatography
on grade 3 alumina, and recrystallization from chloroform−
hexanes, dicarbaporphyrinoid 44a was isolated in 19% yield.
Much better results were obtained with tert-butyl-substituted
fulvene dialdehyde 37b. This reacted with 18a under the same
conditions to give tert-butylcarbaazuliporphyrin 44b in 80%
yield. Dialdehyde 37b similarly condensed with dipyrryl-
methane 18b to give 44c in 46% yield, while reaction of
dipyrrylmethane 18c with 37b afforded 44d in 38% yield. No
oxidation step is required in these reactions. The reaction of
dialdehyde 22 with 18a (Scheme 6) initially results in the
formation of a dihydroporphyrinoid, and this necessitates an
oxidation with ferric chloride. However, as fulvenes 37 are
Figure 1. UV−vis spectra of 22-carbaazuliporphyrin 44b in 1% Et3N−
chloroform (free base, blue line) and 5% TFA-chloroform (dication
44bH2 2+, red line).
carbaazuliporphyrins also exhibit diatropic character that is
comparable to azuliporphyrins 3 and 27. Porphyrinoid 44a is
poorly soluble in organic solvents but a proton NMR spectrum
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could be obtained in CDCl3. This showed the internal azulene
and indene protons as broad comparatively upfield resonances
at 3.44 and 1.6 ppm, respectively, while the external meso-
protons gave rise to downfield singlets at 7.52 (15-H), 7.99
(10-H), 8.56 (20-H), and 9.15 ppm (5-H). In some spectra, the
NH resonance could be observed as a very broad peak at
4.3 ppm. The diatropic characteristics of this system are attribu-
ted to dipolar resonance contributors such as 44′ (Scheme 14)
that possess 18π electron delocalization pathways. tert-Butyl-
substituted carbaazuliporphyrin 44b showed slightly enhanced
diatropicity, showing the internal CH resonances at 3.03 and
1.15 ppm (Figure 2). The meso-protons are also shifted further
Addition of trace amounts of TFA to the NMR solutions of
44a−d generated the corresponding cations 44H+, and these
showed greatly increased diatropic character (Scheme 15). For
Scheme 15
instance, 44bH+ showed the resonances for the internal azulene
and indene protons further upfield at −1.13 and −0.36 ppm,
while the meso-protons shifted downfield to give four 1H
singlets at 8.26, 8.66, 9.06, and 9.28 ppm. Further addition of
TFA led to C-protonation and generated the corresponding
dications 44H22+. For 44aH22+, the internal azulene proton was
observed at −0.08 while the indene derived methylene unit
appeared at −2.76 ppm, confirming that this species also retains
substantial diatropicity. The meso-protons were also observed
further downfield at 9.51 (15-H), 10.00 (10-H), 10.32 (20-H),
and 10.37 ppm (5-H). The aromatic characteristics of the
mono- and dicationic species 44H+ and 44H22+ were attributed
to tropylium-containing species such as 44′H+ and 44′H22+ that
facilitate charge delocalization as well as possessing 18π
electron delocalization pathways.42 The proton NMR spectrum
Figure 2. 500 MHz proton NMR spectrum of 22-carbaazuliporphyrin
44bH2 in CDCl3.
downfield giving rise to four 1H singlets at 7.61, 8.08, 8.65, and
9.23 ppm. These data are consistent with the electron-donating
tert-butyl group stabilizing dipolar canonical forms such as 44b′,
and similar trends have been observed for azuliporphyrins 3. In
pyridine-d5, the meso-protons for 44a shifted downfield to
between 9.0 and 10.5 ppm, indicating that this relatively polar
solvent further stabilizes resonance contributors like 44a′. It
is worth noting that two tautomeric forms are possible, 44
and 44t (Scheme 14), but the spectroscopic data could not
distinguish between these two possibilities. It may be that both
forms are actually present in solution and that they rapidly
interconvert on the NMR time scale. The carbon-13 NMR
spectra for 44 were also consistent with the proposed
asymmetrical porphyrinoid structures. Although carbaazulipor-
phyrin 44a was insufficiently soluble in CDCl3 to produce a
carbon-13 NMR spectrum, 44b−d gave reasonable quality
carbon-13 NMR spectra. Dicarbaporphyrinoid 44b gave a
resonance for the internal indene carbon (C-22) at 122.4 ppm,
while the interior azulene carbon (C-21) showed up at 129.9
ppm. These assignments were made using the HSQC spectrum.
The meso-carbons were observed at 90.1 (C-15), 97.3 (C-10),
106.7 (C-20) and 111.5 ppm (C-5). Dicarbaporphyrinoids 44c
and 44d gave similar results to 44b and will not be discussed
further.
2+
for tert-butyl dicarbaporphyrinoid dication 44bH2 showed
slightly enhanced diatropicity compared to 44aH22+, and the
internal azulene and indene protons were shifted further upfield
to −0.35 (1H) and −2.91 ppm (2H) (Figure 3). In addition,
the meso-protons moved further downfield showing up as four
1H singlets at 9.60, 10.07, 10.32, and 10.41 ppm. Additional
insights can be obtained from the chemical shifts for peripheral
substituents. For instance, methyl substituents attached to
porphyrins generally afford resonances at 3.5−3.6 ppm, while
those attached to nonaromatic systems such as benziporphyrin
appear near 2.4 ppm. In the free base forms, 44a gave two 3H
singlets for the methyl groups at 2.87 and 2.89 ppm, while 44b
gave these resonances at 2.92 and 3.03 ppm. The
2+
2+
corresponding dications 44aH2 and 44bH2 gave these
resonances at 3.26 and 3.29 ppm and 3.31 and 3.32 ppm,
respectively. These data are not only consistent with greatly
enhanced diatropicity in the diprotonated forms but also
suggest that the tert-butyl grouping slightly increases diatropic
character for both the free base forms 44 and the dications
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Scheme 16
Figure 3. Partial 500 MHz proton NMR spectrum of 22-
carbaazuliporphyrin dication 44bH22+ in TFA−CDCl3 showing details
of the upfield and downfield regions.
44H22+. The carbon-13 NMR spectra for dications 44H22+ were
2+
also obtained in TFA−CDCl3. Dication 44aH2 showed the
internal CH2 at 37.3 ppm, the internal azulene carbon gave a
resonance at 129.4 ppm, and the meso-carbons afforded four
peaks at 105.7 (C-10), 106.7 (C-15), 111.9 (C-5), and 118.7
2+
ppm (C-20). Similarly, 44bH2 in TFA−CDCl3 gave the 22-
CH2 resonance at 37.2 ppm, the C-21 peak at 128.5 ppm, and
the meso-resonances at 105.6 (C-10), 106.8 (C-15), 111.8
(C-5) and 118.0 ppm (C-20). The UV−vis spectrum for dica-
46b > 48b. Presumably, the electron-donating tert-butyl
substituent preferentially stabilizes dication 49.
2+
tions 44a-dH2 show strong absorptions near 380, 420, and
740 nm. For instance, 44bH22+ in 5% TFA−CHCl3 gave strong
absorptions at 383, 421, and 737 nm (Figure 1).
The CHCHNHN core of 22-carbaazuliporphyrins 44 could
conceivably act as an organometallic ligand. In fact, doubly
N-confused porphyrins 16a and 16b, which have a similar
core arrangement, have been shown to form silver(III) and
copper(III) complexes,27,28 and a diazuliporphyrin afforded
a palladium(II) derivative.43 Dicarbaporphyrinoid 44b was
reacted with silver(I) acetate in dichloromethane−methanol in
an attempt to generate the corresponding silver(III) complex
(Scheme 17). However, no evidence for a metalation reaction
When TFA-d was added to a solution of 44a in CDCl3 at
room temperature, proton NMR spectroscopy immediately
showed that deuterium exchange with the 22-CH had occurred.
Over a period of several hours at room temperature, the
2+
resonance at 9.51 ppm for the dicationic species 44aH2
showed a substantial decrease in intensity, demonstrating that
deuterium exchange had occurred at the 15-position. This is
presumably due to a low concentration of a C-protonated
species like dication 45 being in equilibrium with 44aH+ and
Scheme 17
2+
44aH2 (Scheme 16), although a related monoprotonated
structure may be involved. After 1 day, the intensities of all of
the meso-resonances were reduced indicating that additional C-
protonated species 46−48 were also present in solution.
Deuterium exchange at position 5 between the azulene and
indene rings was very slow, while exchange at positions 10 and
20 occurred at intermediary rates. Proton exchange was also
observed at the interior azulene CH (21-H), although this
was slower than the exchange at positions 10 and 20, and at
room temperature the 21-CH resonance showed a significant
decrease in intensity several hours after the addition of TFA-d.
Deuterium exchange at position 21, although unexpected, can
be attributed to the presence of a 22π electron delocalized
was obtained and instead a selective oxidation reaction
occurred. Following column chromatography on grade 3
alumina, a dimethoxy derivative was isolated. This species
appeared to be nonaromatic and showed six 1H singlets at
6.130, 6.133, 6.60, 6.87, 7.03, and 8.65 ppm. High-resolution
electrospray ionization mass spectrometry gave a quasimolec-
ular ion at m/z 623.3634 that corresponded to the [M + H]
peak for C43H46N2O2. Selective oxidations have been observed
in monocarbaporphyrinoid systems, and these reactions
commonly occur on the internal carbon atoms. For this reason,
we had anticipated that a similar oxidation process was
occurring for 44b. However, a careful analysis of the product
dication 49 (Scheme 16). The data indicates that the stability of
2+
dications 44aH22+ and 45-49 falls into the sequence 44aH2
≫
45a > 47a > 46a > 49a > 48a. Even after several days, little sign
of degradation was observed, but after 1 week additional peaks
were noted suggesting that some decomposition had occurred.
Similar results were obtained for the tert-butyl-substituted
dicarbaporphyrinoid 44b, although in this case exchange at the
internal azulene CH occurred slightly faster than at positions 10
and 20 and the results indicate that the relative stability of the
dications falls into the sequence 44bH22+ ≫ 45b > 49b > 47b >
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411.1832. Anal. Calcd for C27H25NO3: C, 78.81; H, 6.12; N, 3.40.
Found: C, 78.46; H, 6.02; N, 3.57.
using NOE difference proton NMR spectroscopy demonstrated
that the methoxy units were attached to the 5,20-positions, and
the resulting derivative was assigned as structure 50a. Only a
single diastereomer was isolated, but the NMR data could not
be used to determine whether the cis or trans isomers had been
formed. This unusual product was not very stable and 50a
could not be isolated in pure form. The reaction of 44b with
silver(I) acetate was also carried out in ethanol and the related
diethoxy compound 50b was generated. In this case, a pure
sample of the diethoxy derivative could be isolated in 41% yield.
tert-Butyl 4-Ethyl-5-(1-azulenylmethyl)-3-methylpyrrole-2-
carboxylate (24b). Azulene (170 mg, 1.33 mmol) and tert-butyl
5-acetoxymethyl-4-ethyl-3-methylpyrrole-2-carboxylate47 (23b, 370
mg, 1.32 mmol) were dissolved in 2-propanol (20 mL) and acetic
acid (2 mL), and the solution was refluxed with stirring under nitrogen
for 16 h. The solvent was evaporated under reduced pressure and the
residue purified by column chromatography on silica eluting initially
with 50% dichloromethane−hexanes and then with gradually increased
proportions of CH2Cl2. Initially, a blue fraction corresponding to
unreacted azulene was collected, followed by a major blue band for the
title compound. A third blue band corresponding to an azulitripyrrane
byproduct was also collected. The main product was recrystallized
from 90% ethanol to give azulimethylpyrrole 24b (260 mg, 0.745
CONCLUSIONS
■
Syntheses of azulene appended fulvenes have been investigated,
and a series of fulvene aldehydes have been prepared by
reacting azulene monoaldehydes with an indene-derived
enamine 38 in the presence of di-n-butylboron triflate. Fulvene
dialdehydes could also be conveniently generated by reacting
1,3-azulenedicarbaldehydes with enamine 38 and Bu2BOTf.44
These dialdehydes were condensed with dipyrrylmethane
dicarboxylic acids in the presence of TFA to give a new class
of dicarbaporphyrinoids with adjacent azulene and indene
subunits. These carbaazuliporphyrins exhibited UV−vis spectra
that closely resemble those previously reported for azulipor-
phyrins. The dicarbaporphyrinoids have significant diatropic
character that is slightly enhanced by the presence of an
electron-donating tert-butyl moiety on the azulene subunit. The
diatropicity is further increased upon protonation, and in the
presence of excess TFA a C-protonated dication is generated. In
addition, oxidation of a 22-carbaazuliporphyrin with silver(I)
acetate in alcohol solvents afforded unique nonaromatic
dialkoxy-derivatives. These studies demonstrate that adj-
dicarbaporphyrinoid systems are easily formed by the “2 + 2”
MacDonald condensation, and this approach will make related
porphyrinoid systems available for study.45 In addition, the
robust nature of these porphyrin analogues compared to
previously synthesized opp-dicarbaporphyrinoids shows great
promise for future investigations.
1
mmol, 56%) as dark blue crystals: mp 112−113 °C; H NMR (500
MHz, CDCl3) δ 1.11 (3H, t, J = 7.5 Hz), 1.48 (9H, s), 2.28 (3H, s),
2.53 (2H, q, J = 7.5 Hz), 4.37 (2H, s), 7.10−7.16 (2H, two
overlapping triplets), 7.35 (1H, d, J = 3.8 Hz), 7.58 (1H, t, J = 9.9 Hz),
7.71 (1H, d, J = 3.8 Hz), 8.15 (1H, br s), 8.24 (1H, d, J = 9.7 Hz), 8.30
(1H, d, J = 9.6 Hz); 13C NMR (CDCl3) δ 10.7, 15.8, 17.6, 24.5, 28.7,
80.2, 117.3, 118.6, 122.4, 123.0, 123.4, 125.6, 126.0, 131.8, 133.5,
136.3, 137.1, 137.95, 137.97, 141.2, 161.6; HRMS (EI) calcd for
C23H27NO2 349.2042, found 349.2041. Anal. Calcd for
C23H27NO2·1/10H2O: C, 78.64; H, 7.80; N, 3.99. Found: C, 78.69;
H, 7.83; N, 4.14.
4-Ethyl-5-(3-formyl-1-azulenylmethyl)-3-methylpyrrole-2-
carbaldehyde (22). The foregoing azulenylmethylpyrrole (260 mg,
0.745 mmol) was stirred with TFA (5 mL) for 10 min, diluted with
dichloromethane (20 mL), and washed sequentially with water and
10% aqueous sodium bicarbonate solution. The organic solution as
dried over sodium sulfate, filtered, and evaporated under reduced
pressure. Phosphorus oxychloride was added dropwise to DMF (0.3
mL) in a 50 mL round-bottom flask while the temperature was
maintained between 10 and 20 °C with the aid of an ice bath. The
mixture was allowed to stand for 15 min at room temperature. The
deprotected azulenylmethylpyrrole 26 in dichloromethane (20 mL)
was added dropwise over 10 min. The resulting mixture was stirred at
room temperature for 10 min, and then a solution of sodium acetate
trihydrate (11.0 g) in water (20 mL) was added. The resulting biphasic
mixture was stirred under reflux for 15 min. The mixture was cooled,
the organic layer separated, and the aqueous phase extracted with
chloroform. The combined organic layers were washed with saturated
sodium bicarbonate solution, dried over sodium sulfate, and
evaporated under reduced pressure. The residue was recrystallized
from ethanol to give the dialdehyde (138 mg, 0.452 mmol, 61%) as red
crystals: mp 176−178 °C; 1H NMR (500 MHz, CDCl3) δ 1.09 (3H, t,
J = 7.6 Hz), 2.29 (3H, s), 2.50 (2H, q, J = 7.6 Hz), 4.36 (2H, s), 7.50
(1H, t, J = 9.8 Hz), 7.63 (1H, t, J = 9.8 Hz), 7.87 (1H, t, J = 9.8 Hz),
8.04 (1H, s), 8.38 (1H, d, J = 9.8 Hz), 8.89 (1H, br s), 9.41 (1H, s),
9.56 (1H, d, J = 9.8 Hz), 10.30 (1H, s); 13C NMR (CDCl3) δ 8.9, 15.4,
17.3, 24.6, 124.9, 126.1, 128.2, 128.5, 130.0, 135.9, 136.4, 137.9, 140.4,
141.4, 142.2, 142.5, 176.3, 186.3; HRMS (EI) calcd for C20H19NO2
305.1416, found 305.1413.
3-Chloroazulene-1-carbaldehyde (29c). A solution of N-
chlorosuccinimide (1.052 g, 7.88 mmol) in dichloromethane (50
mL) was added dropwise to a stirred solution of azulene (1.008 g, 7.88
mmol) in dichloromethane (30 mL), and the mixture was stirred at
room temperature overnight. The solution was washed with water
(2 × 100 mL), dried over sodium sulfate, and evaporated under
reduced pressure to give crude 1-chloroazulene. Phosphorus oxy-
chloride (6.5 mL) was added dropwise to DMF (10 mL), maintaining
the temperature between 10 and 20 °C with the aid of an ice bath. The
resulting solution of the Vilsmeier reagent was allowed to stand at
room temperature for 10 min and then added dropwise over 3 min to
a stirred solution of the crude 1-chloroazulene in DMF (60 mL). The
mixture was stirred for 15 min at room temperature and poured into
100 mL of ice−water. The mixture was basified with 20% aqueous
sodium hydroxide solution and then extracted with dichloromethane.
The organic phase was washed with water, dried over sodium sulfate,
EXPERIMENTAL SECTION46
■
Benzyl 4-Ethyl-5-(3-formyl-1-azulenylmethyl)-3-methylpyr-
role-2-carboxylate (25). Phosphorus oxychloride (0.25 g) was
added dropwise to stirred DMF (0.12 mL) in a 10 mL round-bottom
flask while the temperature was maintained between 10 and 20 °C. A
solution of benzyl ester 24a6b (100 mg, 0.26 mmol) in 2.4 mL of
dichloromethane was then added over a period of 5 min, and the
resulting mixture was allowed to stir for 10 min at room temperature.
Sodium acetate trihydrate (1.1 g) in water (2 mL) was added, and the
resulting biphasic mixture was stirred vigorously under reflux for 15
min. The mixture was cooled, diluted with dichloromethane, and
washed with saturated sodium carbonate solution. The organic layer
was separated and dried over sodium sulfate and the solvent removed
under reduced pressure. The residue was purified by column chro-
matography on silica, eluting initially with 80% dichloromethane−
chloroform and then with chloroform. The product fraction was
evaporated and the residue recrystallized from ethanol to give the
aldehyde (71 mg, 0.17 mmol, 66%) as dark blue crystals: mp 138−
139 °C; 1H NMR (500 MHz, CDCl3) δ 1.07 (3H, t, J = 7.5 Hz), 2.33
(3H, s), 2.49 (2H, q, J = 7.5 Hz), 4.32 (2H, s), 5.22 (2H, s), 7.26−7.35
(5H, m), 7.50 (1H, t, J = 9.8 Hz), 7.61 (1H, t, J = 9.8 Hz), 7.86 (1H, t,
J = 9.9 Hz), 8.02 (1H, s), 8.39 (1H, d, J = 9.8 Hz), 8.45 (1H, br s),
9.55 (1H, d, J = 9.7 Hz), 10.30 (1H, s); 13C NMR (CDCl3) δ 10.8,
15.7, 17.6, 24.5, 65.7, 117.6, 124.4, 124.8, 127.2, 127.6, 128.1, 128.2,
128.7, 129.9, 131.4, 136.0, 136.7, 137.8, 140.3, 141.4, 142.2, 142.4,
161.6, 186.4; HRMS (EI) calcd for C27H25NO3 411.1834, found
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and then evaporated under reduced pressure, initially using a water
aspirator and then switching over to an oil pump to remove residual
DMF. The residue was purified on a silica column, eluting with 30%
hexanes−dichloromethane. A blue band corresponding to dichlor-
oazulene was collected initially, followed by a dark purple band
corresponding to the product. Recrystallization from hexanes gave the
aldehyde (1.033 g, 5.42 mmol, 69%) as dark red-purple crystals: mp
115−116 °C; 1H NMR (500 MHz, CDCl3) δ 7.60 (1H, t, J = 9.8 Hz),
7.64 (1H, t, J = 9.9 Hz), 7.91 (1H, t, J = 9.9 Hz), 8.14 (1H, s), 8.57
(1H, d, J = 9.9 Hz), 9.55 (1H, d, J = 9.9 Hz), 10.29 (1H, s); 13C NMR
(CDCl3) δ 118.8, 123.7, 128.6, 130.2, 137.0, 138.6, 139.1, 139.3, 139.8,
141.4, 185.8. Anal. Calcd for C11H7ClO: C, 69.31; H, 3.70. Found:
C, 69.34; H, 3.57.
3-Bromoazulene-1-carbaldehyde (29d). A solution of the
Vilsmeier reagent, prepared as described above from phosphorus
oxychloride (1.5 mL) and DMF (10 mL), was added dropwise to a
solution of azulene (0.250 g, 1.95 mmol) in DMF (15 mL), and the
mixture was stirred for 2 h. The solution was poured into 40 mL of
ice−water and basified with 20% sodium hydroxide solution. The
mixture was extracted with chloroform, washed with water, dried over
sodium sulfate, and evaporated under reduced pressure to give
1-azulenecarbaldehyde. A solution of N-bromosuccinimide (0.357 g)
in dichloromethane (25 mL) was added dropwise to a stirred solution
of the crude aldehyde in dichloromethane (25 mL), and the mixture
was stirred for 20 min. The solution was washed with water and dried
over sodium sulfate and the solvent removed under reduced pressure.
Recrystallization from hexanes gave the aldehyde (0.220 g, 0.94 mmol,
48%) as purple needles: mp 103−104 °C; 1H NMR (500 MHz,
CDCl3) δ 7.62 (1H, t, J = 9.8 Hz), 7.64 (1H, t, J = 9.9 Hz), 7.90 (1H,
t, J = 9.9 Hz), 8.21 (1H, s), 8.54 (1H, d, J = 9.9 Hz), 9.54 (1H, d,
J = 9.7 Hz), 10.26 (1H, s); 13C NMR (CDCl3) δ 106.3, 125.0, 128.9,
130.4, 138.3, 138.7, 139.8, 141.3, 141.6, 142.7, 185.8. Anal. Calcd for
C11H7BrO: C, 55.97; H, 2.99. Found: C, 56.05; H, 2.85.
3-Iodoazulene-1-carbaldehyde (29e). The iodoazulene alde-
hyde was prepared by the procedure used to prepared 29c from
azulene (1.00 g, 7.8 mmol) and N-iodosuccinimide (1.85 g, 95%, 7.8
mmol). Recrystallization from hexanes gave the iodo aldehyde (1.837
g, 6.51 mmol, 83%) as red-brown crystals: mp 104−105 °C; 1H NMR
(500 MHz, CDCl3) δ 7.67−7.73 (2H, two overlapping triplets), 7.95
(1H, t, J = 9.9 Hz), 8.39 (1H, s), 8.50 (1H, d, J = 9.9 Hz), 9.58 (1H, d,
J = 9.8 Hz), 10.30 (1H, s); 13C NMR (CDCl3) δ 76.9, 127.3, 129.2,
130.7, 137.6, 140.4, 141.0, 141.4, 145.2, 149.0, 185.8. Anal. Calcd for
C11H7IO: C, 46.84; H, 2.50. Found: C, 46.97; H, 2.21.
6-tert-Butyl-3-iodoazulene-1-carbaldehyde (29f). The title
compound was prepared by the previous procedure from 6-tert-
butylazulene6c (280 mg, 1.52 mmol) and N-iodosuccinimide (360 mg,
95%, 1.52 mmol). Recrystallization from hexanes gave the aldehyde
(231 mg, 0.683 mmol, 45%) as red-purple needles: mp 76−77 °C; 1H
NMR (500 MHz, CDCl3) δ 1.50 (9H, s), 7.87 (2H, d, J = 10.7 Hz),
8.28 (1H, s), 8.41 (1H, d, J = 10.8 Hz), 9.48 (1H, d, J = 10.7 Hz),
10.25 (1H, s); 13C NMR (CDCl3) δ 32.0, 39.4, 76.0, 127.2, 127.8,
128.6, 136.8, 139.3, 140.2, 144.1, 144.1, 147.9, 166.1, 185.7; HRMS
(EI) calcd for C15H15IO 338.0168, found 338.0170.
reagent was allowed to stand at room temperature for 10 min and then
added dropwise over 3 min to a stirred solution of the foregoing
cyanovinylazulene 42 (1.80 g, 7.17 mmol) in DMF (8 mL). The
mixture was stirred for 15 min at room temperature and poured into
50 mL of ice−water. The mixture was basified with 20% aqueous
sodium hydroxide solution and then extracted with dichloromethane.
The organic phase was washed with water, dried over sodium sulfate,
and then evaporated under reduced pressure, initially using a water
aspirator and then switching over to an oil pump to remove residual
DMF. Recrystallization from ethanol gave the aldehyde (1.77 g, 6.34
1
mmol, 88%) as a red-brown solid: mp 218−219 °C; H NMR (500
MHz, CDCl3) δ 1.43 (3H, t, J = 7.1 Hz), 4.41 (2H, q, J = 7.1 Hz), 7.89
(1H, t, J = 9.9 Hz), 7.92 (1H, t, J = 9.8 Hz), 8.12 (1H, t, J = 9.8 Hz),
8.81 (1H, s), 8.88 (1H, d, J = 9.9 Hz), 9.40 (1H, s), 9.90 (1H, d, J =
9.8 Hz), 10.39 (1H, s); 13C NMR (CDCl3) δ 14.5, 62.6, 98.0, 117.5,
121.1, 127.9, 131.9, 134.2, 136.3, 140.8, 142.5, 143.2, 143.9, 144.2,
147.1, 164.0, 188.2. Anal. Calcd for C17H13NO3: C, 73.11; H, 4.69; N,
5.01. Found: C, 73.00; H, 4.50; N, 5.06.
6-(6-tert-Butyl-1-azulenyl)benzo[a]fulvene (34b). A solution
of potassium hydroxide in methanol (1% w/v, 8 mL) was added to a
stirred solution of 6-tert-butylazulene-1-carbaldehyde (250 mg, 1.18
mmol) and indene (385 mg, 3.32 mmol) in methanol (15 mL), and
the resulting mixture was stirred under nitrogen for 2 days. The
mixture was diluted with dichloromethane, washed with water, and
dried over sodium sulfate. Following evaporation of the solvent under
reduced pressure (water aspirator) and removal of excess indene with
an oil pump, the residue was purified by column chromatography on
silica, eluting with toluene. An initial orange fraction was discarded,
and the product was collected as a green band. Recrystallization from
hexanes gave the fulvene (330 mg, 1.06 mmol, 90%) as lustrous dark
green needles: mp 158−159 °C; 1H NMR (500 MHz, CDCl3) δ 1.48
(9H, s), 7.04 (1H, d, J = 5.5 Hz), 7.22−7.25 (2H, m), 7.33 (1H, d, J =
5.5 Hz), 7.36−7.38 (1H, m), 7.40−7.43 (2H, m), 7.50 (1H, dd, J =
1.6, 10.5 Hz), 7.82−7.84 (1H, m), 8.07 (1H, s), 8.25 (1H, d, J = 10.2
Hz), 8.34 (1H, d, J = 4.2 Hz), 8.61 (1H, d, J = 10.6 Hz); 13C NMR
(CDCl3) δ 32.0, 38.9, 118.8, 120.2, 121.07, 121.12, 123.2, 123.6, 124.7,
126.1, 126.4, 126.8, 132.2, 133.4, 135.8, 136.7, 137.3, 138.3, 138.5,
141.6, 142.4, 163.3. Anal. Calcd for C24H22: C, 92.86; H, 7.14. Found:
C, 92.87; H, 7.08.
Difulvene 35. The difulvene was prepared by the foregoing
procedure by reacting 1,3-azulenedicarbaldehyde37 (400 mg, 2.17
mmol) with indene (1.28 g, 11.0 mmol) in methanol (48 mL) with 24
mL of 1% potassium hydroxide in methanol. Recrystallization from
dichloromethane−hexanes gave the title compound (671 mg, 1.76
1
mmol, 81%) as dark purple crystals: mp 220−222 °C, dec; H NMR
(500 MHz, CDCl3) δ 7.10 (2H, dd, J = 1.2, 5.5 Hz), 7.25−7.28 (6H,
m), 7.33 (2H, t, J = 9.9 Hz), 7.36−7.40 (2H, m), 7.71 (1H, t, J = 9.8
Hz), 7.81−7.85 (2H, m), 8.00 (2H, s), 8.59 (2H, d, J = 9.9 Hz), 8.77
(1H, s); 13C NMR (CDCl3) δ 119.1, 119.9, 121.3, 125.1, 126.5, 126.6,
127.2, 127.5, 133.9, 135.1, 138.0, 138.4, 139.4, 140.3, 141.7, 142.0;
HRMS (EI) calcd for C30H20 380.1565, found 380.1567. Anal. Calcd
for C30H20: C, 94.70; H, 5.30. Found: C, 94.26; H, 5.17.
6-(6-tert-Butyl-1-azulenyl)benzo[a]fulvene-3-carbaldehyde
(39b). Dibutylboron triflate (1.0 M in dichloromethane, 1.2 mL) was
added to a stirred mixture of 6-tert-butylazulene-1-carbaldehyde (200
mg, 0.943 mmol) and sodium sulfate in 1,2-dichloroethane (300 mL).
A solution of indene enamine 38 (143 mg, 0.836 mmol) in 1,
2-dichloroethane (50 mL) was then added dropwise over 10 min, and
the resultant solution was stirred under reflux for 4 h. Saturated
sodium acetate solution (120 mL) was added, and the mixture was
allowed to stir for 10 min. The solution changed color from greenish
red to dark red. The mixture was extracted with dichloromethane,
washed with saturated sodium bicarbonate solution, and then dried
over sodium sulfate. The solvent was removed under reduced pressure,
and the residue was purified by column chromatography on silica
eluting with 30% hexanes−dichloromethane. Recrystallization from
chloroform−-hexanes gave the fulvene aldehyde (161 mg, 0.476 mmol,
Ethyl 3-(1-Azulenyl)-2-cyano-2-propenoate (42). 1-Azulene-
carbaldehyde (1.21 g, 7.75 mmol) was heated under reflux with ethyl
cyanoacetate (1.0 mL) and six drops of piperidine in ethanol (14 mL)
for 16 h. The mixture was cooled in an ice bath and filtered to give the
Knoevenagel condensation product. Recrystallization from ethanol
gave the cyanovinylazulene (1.895 g, 7.55 mmol, 97%) as red-brown
crystals: mp 116−117 °C; 1H NMR (500 MHz, CDCl3) δ 1.41 (3H, t,
J = 7.1 Hz), 4.39 (2H, q, J = 7.1 Hz), 7.53−7.57 (3H, m), 7.59 (1H, t,
J = 9.9 Hz), 8.47 (1H, d, J = 9.6 Hz), 8.73 (1H, d, J = 9.8 Hz), 8.82
(1H, s), 9.07 (1H, d, J = 4.5 Hz); 13C NMR (CDCl3) δ 14.6, 62.2,
94.8, 118.3, 121.9, 122.5, 128.2, 129.1, 134.2, 137.9, 138.8, 140.2,
143.6, 144.1, 146.1, 164.9. Anal. Calcd for C16H13NO2: C, 76.48; H,
5.21; N, 5.57. Found: C, 76.24; H, 5.06; N, 5.67.
Ethyl 2-Cyano-3-(3-formyl-1-azulenyl)-2-propenoate (43).
Phosphorus oxychloride (1.36 g) was added dropwise to DMF
(4 mL) while the temperature was maintained between 10 and 20 °C
with the aid of an ice bath. The resulting solution of the Vilsmeier
1
57%) as dark purple crystals: mp 198−200 °C dec; H NMR (500
MHz, CDCl3) δ 1.50 (9H, s), 7.31−7.36 (2H, m), 7.48 (1H, d, J = 4.4
Hz), 7.57 (1H, dd, J = 1.8, 10.2 Hz), 7.66 (1H, dd, J = 1.8, 10.7 Hz),
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Article
7.85−7.88 (1H, m), 8.03 (1H, s), 8.15−8.18 (1H, m), 8.33 (1H, d, J =
10.3 Hz), 8.37 (1H, s), 8.42 (1H, d, J = 4.3 Hz), 8.69 (1H, d, J = 10.7
Hz), 10.22 (1H, s); 13C NMR (CDCl3) δ 32.0, 39.1, 118.7, 121.9,
122.8, 125.3, 125.7, 125.8, 125.9, 126.8, 128.3, 133.1, 133.7, 136.5,
137.50, 137.54, 138.9, 140.26, 140.29, 140.4, 144.0, 164.6, 189.0;
HRMS (EI) calcd for C25H22O 338.1671, found 338.1678.
7.49−7.54 (2H, two overlapping triplets), 7.85 (1H, t, J = 9.9 Hz),
7.86−7.89 (1H, m), 7.95 (1H, s), 8.16−8.19 (1H, m), 8.25 (1H, s),
8.38 (1H, d, J = 9.7 Hz), 8.58 (1H, s), 8.66 (1H, d, J = 9.8 Hz), 10.28
(1H, s); 13C NMR (CDCl3) δ 80.7, 119.1, 123.0, 126.1, 126.3, 127.18,
127.22, 127.4, 127.9, 134.3, 135.1, 136.9, 138.5, 139.6, 140.8, 141.0,
141.6, 143.8, 145.2, 189.1; HRMS (EI) calcd for C21H13IO 408.0012,
found 408.0018.
6-(3-Chloro-1-azulenyl)benzo[a]fulvene-3-carbaldehyde
(39c). Dibutylboron triflate (1.0 M in dichloromethane, 0.90 mL) was
added to a stirred solution of 3-chloroazulene-1-carbaldehyde (150
mg, 0.787 mmol) in dichloromethane (100 mL). A solution of indene
enamine 38 (150 mg, 0.877 mmol) in dichloromethane (50 mL) was
then added dropwise over 10−20 min, and the resultant solution was
stirred at room temperature for 16 h. Saturated sodium acetate
solution (100 mL) was added, and the solution turned from dark blue
to red. The mixture was allowed to stir for 10 min and then extracted
with dichloromethane and washed with saturated sodium bicarbonate
solution. The organic phase was dried over sodium sulfate, the solvent
was removed under reduced pressure, and the residue was purified by
column chromatography on silica eluting with 30% hexanes−
dichloromethane. Recrystallization with chloroform−hexanes gave
the fulvene aldehyde (147 mg, 0.464 mmol, 59%) as a dark red-
purple solid: mp >260 °C; 1H NMR (500 MHz, CDCl3) δ 7.32−7.36
(2H, m), 7.41 (2H, t, J = 9.8 Hz), 7.79 (1H, t, J = 9.8 Hz), 7.82−7.85
(1H, m), 7.91 (1H, s), 8.12−8.16 (1H, m), 8.23 (1H, s), 8.33 (1H, s),
8.44 (1H, d, J = 9.7 Hz), 8.64 (1H, d, J = 9.9 Hz), 10.22 (1H, s); 13C
NMR (CDCl3) δ 119.0, 121.7, 123.0, 123.6, 126.3, 126.8, 127.3, 127.4,
134.8, 135.3, 135.6, 136.3, 136.7, 138.3, 138.5, 139.5, 139.8, 141.3,
141.4, 189.1; HRMS (EI) calcd for C21H13ClO 316.0655, found
316.0667.
6-(6-tert-Butyl-3-iodo-1-azulenyl)benzo[a]fulvene-3-carbal-
dehyde (39f). N-Iodosuccinimide (370 mg, 95%, 1.56 mmol) was
added to fulvene 39b (358 mg, 1.06 mmol) dissolved in 100 mL of
dichloromethane, and the mixture was stirred for 15 min. The solution
was washed with water and dried over sodium sulfate. The solvent was
removed under reduced pressure and the residue purified by column
chromatography on silica eluting with 30% hexanes−dichloromethane.
Recrystallization from chloroform−hexanes gave the fulvene (444 mg,
0.957 mmol, 90%) as a dark powder: mp 215−216 °C; 1H NMR (500
MHz, CDCl3) δ 1.50 (9H, s), 7.31−7.36 (2H, m), 7.66−7.70 (2H, m),
7.82−7.86 (1H, m), 7.96 (1H, s), 8.14−8.17 (1H, m), 8.22 (1H, s),
8.28 (1H, d, J = 10.7 Hz), 8.48 (1H, s), 8.60 (1H, d, J = 10.7 Hz),
10.24 (1H, s); 13C NMR (CDCl3) δ 31.9, 39.3, 80.2, 118.9, 123.0,
125.8, 126.17, 126.22, 126.4, 126.9, 127.2, 133.5, 134.2. 136.7, 138.6,
139.73, 139.75, 140.0, 141.1, 142.8, 144.1, 165.8, 189.1; HRMS (EI)
calcd for C25H21IO 464.0638, found 464.0641.
6-(6-tert-Butyl-3-formyl-1-azulenyl)benzo[a]fulvene-3-car-
baldehyde (37b). Dibutylboron triflate (1.0 M in dichloromet-
hane, 1.50 mL) was added to a stirred solution of 6-tert-butyl-1,
3-azulenedicarbaldehyde6c (248 mg, 1.03 mmol) in dichloromethane
(300 mL) at 5 °C. A solution of indene enamine 38 (174 mg, 1.02
mmol) in dichloromethane (50 mL) was added dropwise over 10−20
min, and the resulting dark solution was stirred at room temperature
for 16 h. Saturated sodium acetate solution (100 mL) was added, and
the solution turned from dark blue to purple. The mixture was allowed
to stir for 1 h and then extracted with dichloromethane and washed
with saturated sodium bicarbonate solution. The organic phase was
dried over sodium sulfate, the solvent was removed under reduced
pressure, and the residue was purified by column chromatography on
silica eluting with 5% methanol−chloroform and then on a second
silica column eluting with chloroform. A dark orange fraction was
collected and evaporated under reduced pressure. Recrystallization
from acetone-hexanes gave the fulvene dialdehyde (128 mg, 0.350
6-(3-Bromo-1-azulenyl)benzo[a]fulvene-3-carbaldehyde
(39d). The bromofulvene was prepared by the foregoing procedure
from 3-bromoazulene-1-carbaldehyde (102 mg, 0.434 mmol), indene
enamine 38 (78 mg, 0.456 mmol) and dibutylboron triflate (1.0 M in
dichloromethane, 0.40 mL). Recrystallization from chloroform-
hexanes gave the fulvene aldehyde (64 mg, 0.177 mmol, 41%) as a
1
dark purple-red solid, mp >260 °C; H NMR (500 MHz, CDCl3) δ
7.32−7.36 (2H, m), 7.45 (2H, t, J = 9.8 Hz), 7.81 (1H, t, J = 9.9 Hz),
7.83−7.86 (1H, m), 7.91 (1H, s), 8.12−8.16 (1H, m), 8.24 (1H, s),
8.42−8.44 (1H, overlapping singlet and doublet), 8.65 (1H, d, J = 9.8
Hz), 10.23 (1H, s); 13C NMR (CDCl3) δ 109.6, 119.0, 123.0, 124.9,
126.2, 126.3, 126.9, 127.4, 127.6, 134.9, 135.0, 136.8, 138.0, 138.5,
138.8, 139.6, 140.1, 140.4, 141.2, 141.5, 189.1; HRMS (EI) calcd for
C21H13BrO 360.0150, found 360.0132.
1
mmol, 34%) as a dark red-brown solid: mp 233−234 °C; H NMR
(500 MHz, CDCl3) δ 1.54 (9H, s), 7.34−7.38 (2H, m), 7.83−7.87
(1H, m), 7.94 (1H, s), 7.95−7.98 (2H, m), 8.12−8.18 (1H, m), 8.27
(1H, s), 8.68 (1H, s), 8.80 (1H, d, J = 11.0 Hz), 9.62 (1H, d, J = 10.7
Hz), 10.25 (1H, s), 10.46 (1H, s); 13C NMR (CDCl3) δ 32.0, 39.6,
119.1, 123.1, 125.4, 126.5, 127.1, 127.6, 127.7, 129.2, 130.5, 135.8,
136.0, 137.1, 138.3, 138.5, 139.6, 141.7, 141.9, 143.0, 144.0, 167.4,
187.1, 189.2; HRMS (EI) calcd for C26H22O2 366.1620, found
366.1618.
6-(3-(2-Ethoxycarbonyl-2-cyanoethenyl)-1-azulenyl)benzo-
[a]fulvene-3-carbaldehyde (39g). The cyanovinylfulvene was
prepared by the foregoing procedure from 43 (279 mg, 1.00 mmol),
indene enamine 38 (188 mg, 1.10 mmol), and dibutylboron triflate
(1.0 M in dichloromethane, 1.10 mL). Recrystallization from
chloroform−hexanes gave the fulvene aldehyde (330 mg, 0.815
mmol, 81%) as a dark red-brown powder, mp >260 °C; 1H NMR (500
MHz, CDCl3) δ 1.45 (3H, t, J = 7.6 Hz), 4.43 (2H, q, J = 7.6 Hz),
7.33−7.38 (2H, m), 7.68−7.74 (2H, two overlapping triplets), 7.82−
7.85 (1H, m), 7.94 (1H, s), 8.00 (1H, t, J = 9.9 Hz), 8.12−8.15 (1H,
m), 8.19 (1H, s), 8.73 (1H, d, J = 9.9 Hz), 8.79 (1H, s), 8.80 (1H, d,
J = 9.8 Hz), 9.54 (1H, s), 10.16 (1H, s); 13C NMR (CDCl3) δ 14.5,
61.8, 97.2, 118.1, 119.4, 122.9, 123.4, 125.3, 126.6, 128.07, 128.10,
130.4, 130.5, 135.3, 136.4, 137.4, 138.08, 138.12, 138.8, 140.0, 141.8,
143.0, 143.3, 144.2, 145.3, 164.1, 189.6. Anal. Calcd for C17H19NO3:
C, 79.98; H, 4.72; N, 3.45. Found: C, 79.64; H, 4.48; N, 3.58.
6-(3-Iodo-1-azulenyl)benzo[a]fulvene-3-carbaldehyde (39e).
N-Iodosuccinimide (192 mg, 95%, 0.851 mmol) was added to a stirred
solution of fulvene 39a (200 mg, 0.709 mmol) in dichloromethane
(100 mL). Two drops of TFA were added, and the mixture was stirred
for 5 min. The solution was washed with saturated sodium bicarbonate
solution, and the organic phase was dried over sodium sulfate. The
solvent was removed under reduced pressure and the residue purified
by flash chromatography on silica eluting with 30% hexanes−
dichloromethane. Recrystallization from chloroform−hexanes gave
the fulvene (220 mg, 0.539 mmol, 76%) as dark red-brown crystals:
mp 211−212 °C; 1H NMR (500 MHz, CDCl3) δ 7.33−7.37 (2H, m),
7,13,17-Triethyl-8,12,18-trimethylazuliporphyrin (27). Con-
centrated hydrochloric acid (10 drops) was added to a stirred solution
of dipyrrylmethanedicarboxylic acid 18a36 (40 mg, 0.12 mmol) and
dialdehyde 22 (36 mg, 0.12 mmol), and the mixture was stirred under
nitrogen at room temperature overnight. The mixture was diluted
with dichloromethane, washed with water, and then shaken vigorously
with 0.1% aqueous ferric chloride solution. The organic phase was
separated, washed with water and saturated sodium bicarbonate
solution, and evaporated under reduced pressure. The residue was
loaded onto a grade 3 alumina column and eluted with 5% methanol−
chloroform. A deep green fraction was collected, evaporated under
reduced pressure, and recrystallized from chloroform−hexanes to give
the azuliporphyrin (7.5 mg, 0.015 mmol, 13%) as a dark green solid:
mp >300 °C; UV−vis (1% Et3N−CHCl3) λmax (log ε) 355 (4.78), 397
(4.71), 445 (4.70), 472 (4.80), 621 nm (4.21); UV−vis (1% TFA−
CHCl3) λmax (log ε) 365 (4.94), 437 (4.70), 462 (5.03), 642 nm
1
(4.43); H NMR (500 MHz, CDCl3) δ 1.54 (6H, obscured by water
peak), 1.59 (3H, t, J = 7.8 Hz), 2.89 (3H, s), 2.98 (3H, s), 2.99 (3H,
s), 3.33 (2H, q, J = 7.7 Hz), 3.40−3.47 (4H, two overlapping
quartets), 7.58−7.63 (2H, m), 7.69 (1H, t, J = 9.5 Hz), 8.04 (1H, br s),
8.05 (1H, br s), 8.90 (1H, s), 8.92 (1H, s), 9.24 (1H, d, J = 9.6 Hz),
2378
dx.doi.org/10.1021/jo2026977 | J. Org. Chem. 2012, 77, 2368−2381

The Journal of Organic Chemistry
Article
9.25 (1H, d, J = 9.6 Hz); 1H NMR (500 MHz, TFA−CDCl3) δ −2.85
(1H, s), −1.87 (1H, v br), −0.16 (1H, s), −0.15 (1H, s), 1.62 (3H, t,
J = 7.7 Hz), 1.65−1.69 (6H, two overlapping triplets), 3.32 (3H, s),
3.37 (3H, s), 3.43 (3H, s), 3.78−3.85 (4H, two overlapping quartets),
3.90 (2H, q, J = 7.7 Hz), 8.45 (1H, t, J = 9.6 Hz), 8.58 (2H, t, J = 9.6
Hz), 9.47 (1H, s), 9.48 (1H, s), 9.94−9.98 (2H, two overlapping
doublets), 10.33 (1H, s), 10.35 (1H, s); 13C NMR (CDCl3) δ 10.6,
10.8, 10.9, 16.3, 16.5, 17.1, 18.9, 19.1, 19.2, 92.94, 92.98, 107.6, 126.1,
131.6, 134.7, 139.4, 139.8, 141.6, 146.4, 148.5; 13C NMR (TFA−
CDCl3) δ 11.2, 11.5, 11.6, 16.07, 16.15, 16.4, 19.6, 19.9, 20.1, 94.9,
95.4, 109.7, 110.0, 123.9, 128.00, 128.04, 135.8, 139.1, 140.38, 140.42,
140.9, 141.8, 142.38, 142.45, 142.51, 144.2, 145.0, 145.6, 146.4, 147.4,
148.1, 148.9, 153.83, 153.89; HRMS (FAB) calcd for C35H35N3 + H
498.2909, found 498.2911.
8.26 (1H, s), 8.66 (1H, s), 9.06 (1H, s), 9.15 (1H, d, J = 10.7 Hz), 9.20
(1H, d, J = 10.5 Hz), 9.28 (1H, s); H NMR (500 MHz, TFA−
1
CDCl3) δ −2.91 (2H, s), −0.35 (1H, s), 0.89 (1H, br), 1.27 (1H, br),
1.59 (3H, t, J = 7.7 Hz), 1.66 (3H, t, J = 7.8 Hz), 1.73 (9H, s), 3.31
(3H, s), 3.32 (3H, s), 3.71−3.80 (4H, two overlapping quartets), 8.51
(1H, t, J = 7.4 Hz), 8.62 (1H, t, J = 7.5 Hz), 8.89 (1H, dd, J = 1.9, 10.3
Hz), 8.95 (1H, dd, J = 1.9, 10.6 Hz), 9.58−9.61 (3H, m), 9.91 (1H, d,
J = 10.5 Hz), 9.97 (1H, d, J = 10.8 Hz), 10.07 (1H, s), 10.32 (1H, s)
10.41 (1H, s); 13C NMR (CDCl3) δ 10.8, 11.1, 16.2, 16.5, 18.9, 19.1,
31.9, 39.1, 90.1, 97.3, 106.7, 111.5, 119.5, 119.8, 122.4, 125.6, 126.7,
126.8, 128.76, 128.83, 129.9, 134.4, 134.6, 135.2, 136.6, 137.9, 138.8,
139.2, 139.9, 141.1, 142.4, 143.0, 143.8, 164.9; 13C NMR (TFA−
CDCl3) δ 11.1, 11.2, 16.0, 16.1, 19.7, 19.9, 31.5, 37.2, 41.9, 105.6,
106.8, 111.8, 118.0, 123.6, 124.7, 128.5, 131.9, 132.3, 135.0, 135.7,
136.7, 139.3, 139.5, 139.7, 141.2, 141.5, 141.6, 142.1, 142.7, 142.8,
144.0, 145.1, 147.7, 150.6, 153.0, 153.5, 155.8, 156.9, 174.9; HRMS
(EI) calcd for C41H40N2 560.3191, found 560.3197. Anal. Calcd for
C41H40N2·1/10CHCl3: C, 86.20; H, 7.06; N, 4.89. Found: C, 86.19; H,
6.89; N, 5.07.
13,17-Diethyl-12,18-dimethyl-22-carbabenzo[g]-
azuliporphyrin (44a). Dipyrrole dicarboxylic acid 18a (30 mg, 0.094
mmol) was dissolved in TFA (5 mL) and then diluted with
dichloromethane (150 mL). Fulvene dialdehyde 37a (30 mg, 0.097
mmol) was added to the stirred solution, and the mixture was stirred
in the dark under nitrogen for 16 h. The solution was washed with
saturated sodium bicarbonate solution, dried over sodium sulfate, and
evaporated under reduced pressure. The residue was loaded onto a
grade 3 alumina column and eluted with 50% dichloromethane−
chloroform. A bright green fraction was collected and the solvent
evaporated. Recrystallization from chloroform−hexanes gave the
dicarbaporphyrinoid (9.0 mg, 0.018 mmol, 19%) as dark green
crystals: mp >300 °C; UV−vis (free base in 1% Et3N−CHCl3) λmax
(log ε) 368 (4.76), 401 (4.67), 470 (4.68), 496 (4.65), 659 nm (4.09);
UV−vis (monocation 44aH+ in 0.5% TFA−CHCl3) λmax (log ε) 314
(4.51), 373 (4.80), 471 (4.60), 522 (sh, 4.40), 690 nm (4.50); UV−vis
23-tert-Butyl-12,13,17,18-tetramethyl-22-carbabenzo[g]-
azuliporphyrin (44c). Using the previous procedure, dipyrryl-
methane 18b (27 mg, 0.094 mmol) was reacted with fulvene
dialdehyde 37b (30 mg, 0.082 mmol). Recrystallization from
chloroform−hexanes gave the dicarbaporphyrinoid (20 mg, 0.037
mmol, 46%) as a dark green powder: mp >300 °C; UV−vis (1%
Et3N−CHCl3) λmax (log ε) 368 (4.77), 398 (4.67), 470 (4.70), 492
(4.70), 626 (sh, 4.10), 677 nm (4.15); UV−vis (0.1% TFA−CHCl3)
λmax (log ε) 375 (4.83), 474 (4.64), 522 (infl, 4.44), 692 nm (4.55);
UV−vis (5% TFA−CHCl3) λmax (log ε) 382 (4.79), 421 (4.89), 460
(sh, 4.55), 485 (sh, 4.42), 520 (4.24), 670 (sh, 4.24), 737 (4.76), 770
nm (4.41); 1H NMR (500 MHz, CDCl3) δ 1.15 (1H, br s), 1.58 (9H,
s), 2.76 (3H, s), 2.80 (3H, s), 2.87 (6H, s), 3.00 (1H, v br), 7.49−7.54
(3H, m), 7.80 (2H, d, J = 10.5 Hz), 8.02 (1H, s), 8.14−8.17 (1H, m),
8.34−8.37 (1H, m), 8.58 (1H, s), 9.12 (1H, d, J = 10.5 Hz), 9.18−9.21
(2H, m); 1H NMR (500 MHz, TFA−CDCl3) δ −2.72 (2H, s), −0.18
(1H, s), 1.72 (9H, s), 3.20 (3H, s), 3.25 (3H, s), 3.27 (6H, s), 8.47
(1H, t, J = 7.4 Hz), 8.59 (1H, t, J = 7.4 Hz), 8.82 (1H, d, J = 10.1 Hz),
8.88 (1H, d, J = 10.6 Hz), 9.53 (1H, s), 9.54−9.57 (2H, m), 9.86 (1H,
d, J = 10.3 Hz), 9.91 (1H, d, J = 10.6 Hz), 9.97 (1H, s), 10.26 (1H, s),
10.33 (1H, s); 13C NMR (CDCl3) δ 10.6, 11.0, 11.3, 32.0, 39.1, 89.8,
97.4, 106.1, 111.4, 119.4, 119.8, 122.3, 125.4, 126.5, 126.5, 126.6,
128.9, 129.6, 132.3, 134.3, 134.5, 135.7, 136.2, 137.6, 139.4, 139.9,
142.3, 143.1, 143.4, 143.9, 164.8; 13C NMR (TFA−CDCl3) δ 11.3,
11.4, 11.5, 11.7, 31.7, 37.2, 105.6, 107.4, 111.7, 118.3, 123.5, 124.6,
129.1, 131.5, 132.1, 134.6, 135.4, 137.0, 138.5, 139.2, 139.4, 140.4,
140.9, 141.5, 142.0, 142.1, 142.5, 142.7, 143.9, 144.3, 147.6, 152,7,
153.6, 155.4, 157.3; HRMS (EI) calcd for C39H36N2 532.2879, found
532.2882. Anal. Calcd for C39H36N2·1/3CHCl3: C, 82.58; H, 6.40; N,
4.90. Found: C, 82.57; H, 6.29; N, 5.06.
2+
(dication 44aH2 in 5% TFA−CHCl3) λmax (log ε) 388 (4.79), 421
(4.83), 516 (sh, 4.26), 670 (infl, 4.14), 743 (4.64), 779 nm (infl, 4.36);
1H NMR (500 MHz, CDCl3) δ 1.48−1.53 (6H, two overlapping
triplets), 2.87 (3H, s), 2.89 (3H, s), 3.22 (2H, q, J = 7.7 Hz), 3.27 (2H,
q, J = 7.7 Hz), 3.44 (1H, br s), 7.49−7.56 (5H, m), 7.70 (1H, t, J = 9.7
Hz), 7.99 (1H, s), 8.14 (1H, d, J = 6.8 Hz), 8.35 (1H, d, J = 6.8 Hz),
1
8.56 (1H, s), 9.10 (1H, s), 9.15 (1H, s), 9.18 (1H, d, J = 9.8 Hz); H
NMR (500 MHz, TFA−CDCl3): δ −2.76 (2H, s), −0.08 (1H, s), 1.55
(3H, t, J = 7.7 Hz), 1.62 (3H, t, J = 7.7 Hz), 3.26 (3H, s), 3.29 (3H, s),
3.67−3.75 (4H, two overlapping quartets), 8.47 (1H, t, J = 7.5 Hz),
8.56−8.72 (4H, m), 9.51 (1H, s), 9.54 (1H, d, J = 8.1 Hz), 9.57 (1H,
d, J = 8.1 Hz), 9.95 (1H, d, J = 9.4 Hz), 9.99−10.01 (2H, overlapping
singlet and doublet), 10.32 (1H, s), 10.37 (1H, s); 13C NMR (TFA−
CDCl3) δ 11.1, 11.3, 16.0, 16.1, 19.6, 19.9, 105.7, 106.7, 111.9, 118.7,
123.6, 124.8, 129.4, 131.6, 131.9, 135.1, 135.3, 137.0, 140.0, 140.63,
140.67, 141.9, 142.1, 142.6, 142.8, 142.9, 143.5, 144.0, 144.8, 146.8,
147.9, 150.6, 154.1, 154.2, 156.6, 158.0; HRMS (EI) calcd for
C37H32N2 504.2565, found 504.2563.
23-tert-Butyl-13,17-diethyl-12,18-dimethyl-22-carbabenzo-
[g]azuliporphyrin (44b). Using the foregoing procedure, dipyrryl-
methane 18a (30 mg, 0.094 mmol) was reacted with fulvene dialde-
hyde 37b (30 mg, 0.082 mmol). Recrystallization from chloroform−
hexanes gave the dicarbaporphyrinoid (37 mg, 0.066 mmol, 80%) as a
dark green powder: mp >300 °C; UV−vis (free base, 1% Et3N−
CHCl3) λmax (log ε) 368 (4.78), 399 (4.68), 470 (4.70), 494 (4.70),
624 (sh, 4.10), 677 nm (4.16); UV−vis (monocation 44bH+, 0.1%
TFA−CHCl3) λmax (log ε) 314 (4.49), 376 (4.70), 418 (4.46), 473
(4.55), 522 (infl, 4.38), 692 nm (4.41); UV−vis (dication 44bH22+, 5%
TFA−CHCl3) λmax (log ε) 383 (4.79), 421 (4.89), 458 (sh, 4.55), 485
(sh, 4.42), 520 (sh, 4.25), 672 (sh, 4.25), 737 (4.76), 772 nm (sh,
4.40); 1H NMR (500 MHz, CDCl3) δ 1.15 (1H, br s), 1.49−1.54 (6H,
two overlapping triplets), 1.58 (9H, s), 2.90 (3H, s), 2.92 (3H, s), 3.03
(1H, br s), 3.25 (2H, q, J = 7.7 Hz), 3.30 (2H, q, J = 7.7 Hz), 3.74
(1H, v br), 7.49−7.55 (2H, m), 7.61 (1H, s), 7.80−7.82 (2H, m), 8.08
(1H, s), 8.17−8.19 (1H, m), 8.36−8.38 (1H, m), 8.65 (1H, s), 9.15
(1H, d, J = 10.7 Hz), 9.21 (1H, d, J = 10.7 Hz), 9.23 (1H, s); 1H NMR
(500 MHz, trace TFA−CDCl3) δ −1.13 (1H, br s), −0.36 (1H, br s),
1.51−1.57 (6H, two overlapping triplets), 1.59 (9H, s), 2.99 (3H, s),
3.00 (3H, s), 3.42−3.50 (4H, m), 3.74 (1H, v br), 7.38 (1H, t, J = 7.2
Hz), 7.44 (1H, t, J = 7.2 Hz), 7.96−8.00 (2H, m), 8.06−8.09 (1H, m),
23-tert-Butyl-13,17-bis(2-methoxycarbonylethyl)-12,18-di-
methyl-22-carbabenzo[g]azuliporphyrin (44d). Using the pre-
vious procedure, dipyrrylmethane 18c (41 mg, 0.10 mmol) was
reacted with fulvene dialdehyde 37b (30 mg, 0.082 mmol).
Recrystallization from chloroform−hexanes gave the dicarbaporphyr-
inoid (21 mg, 0.031 mmol, 38%) as a dark green powder: mp >300
°C; UV−vis (free base, 1% Et3N−CHCl3) λmax (log ε) 371 (4.80), 398
(sh, 4.70), 474 (4.72), 495 (4.72), 628 (sh, 4.13), 678 nm (4.20);
UV−vis (monocation, 0.1% TFA−CHCl3) λmax (log ε) 314 (4.51),
377 (4.81), 418 (4.51), 472 (4.63), 525 (infl, 4.43), 692 nm (4.55);
UV−vis (dication, 5% TFA−CHCl3) λmax (log ε) 385 (sh, 4.81), 423
(4.91), 461 (sh, 4.58), 486 (sh, 4.47), 520 (4.31), 670 (sh, 4.28),
1
735 nm (4.75); H NMR (500 MHz, CDCl3) δ 0.91 (1H, br s), 1.58
(9H, s), 2.73 (1H, br), 2.91 (2H, t, J = 7.8 Hz), 2.93 (6H, s), 2.94 (2H,
t, J = 7.8 Hz), 3.57 (2H, t, J = 7.8 Hz), 3.63 (2H, t, J = 7.8 Hz), 3.70
(3H, s), 3.71 (3H, s), 7.50−7.55 (2H, m), 7.59 (1H, br s), 7.83 (2H, d,
J = 10.5 Hz), 8.11 (1H, s), 8.17 (1H, d, J = 6.8 Hz), 8.36 (1H, d, J =
1
6.5 Hz), 8.64 (1H, br), 9.10−9.15 (1H, m), 9.18−9.23 (2H, m); H
NMR (500 MHz, TFA−CDCl3) δ −2.94 (2H, s), −0.39 (1H, s), 1.74
(9H, s), 3.07 (2H, t, J = 7.7 Hz), 3.12 (2H, t, J = 7.7 Hz), 3.33 (3H, s),
3.34 (3H, s), 3.750 (3H, s), 3.755 (3H, s), 4.11 (2H, t, J = 7.7 Hz),
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4.14 (2H, t, J = 7.7 Hz), 8.54 (1H, t, J = 7.5 Hz), 8.65 (1H, t, J = 7.5
Hz), 8.94 (1H, dd, J = 1.9, 10.4 Hz), 9.00 (1H, dd, J = 1.9, 10.7 Hz),
9.59−9.63 (2H, two overlapping doublets), 9.89 (1H, s), 9.93 (1H, d,
J = 10.6 Hz), 9.99 (1H, d, J = 10.8 Hz), 10.09 (1H, s), 10.34 (1H, s),
10.43 (1H, s); 13C NMR (CDCl3): δ 11.0, 11.3, 20.9, 21.3, 31.9, 35.7,
36.0, 39.1, 51.9, 52.0, 89.7, 98.0, 107.1, 111.6, 119.5, 119.9, 122.7,
125.4, 125.7, 126.7, 126.9, 129.15, 129.20, 129.8, 134.4, 134.7, 134.9,
136.4, 136.7, 137.2, 137.9, 139.8, 140.8, 142.3, 143.3, 144.1, 165.1,
173.6, 173.9; 13C NMR (TFA−CDCl3) δ 11.25, 11.30, 21.1, 21.3,
31.5, 35.32, 35.37, 37.2, 41.0, 53.4, 105.7, 107.6, 111.9, 123.6, 124.8,
128.5, 132.1, 132.7, 135.2, 136.2, 138.0, 139.2, 139.7, 139.8, 140.3,
141.3, 141.6, 141.9, 142.1, 143.0, 143.3, 144.4, 145.8, 147.8, 153.1,
153.3, 156.1, 157.3, 175.4, 176.2, 176.5; HRMS (EI) calcd for
C45H44N2O4 676.3301, found 676.3315.
AUTHOR INFORMATION
Corresponding Author
*E-mail: tdlash@ilstu.edu.
Notes
■
The authors declare no competing financial interest.
†Conjugated Macrocycles Related to the Porphyrins. 61. For
part 60, see ref 15.
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
under Grant No. CHE-0911699 and the Petroleum Research
Fund, administered by the American Chemical Society.
Funding for a 500 MHz NMR spectrometer was provided
by the National Science Foundation under Grant No. CHE-
0722385.
23-tert-Butyl-13,17-diethyl-5,20-dihydro-5,20-dimethoxy-
12,18-dimethyl-22-carbabenzo[g]azuliporphyrin (50a). A sus-
pension of silver(I) acetate (75 mg, 0.45 mmol) in methanol (25 mL)
was added to a stirred solution of dicarbaporphyrin 44b (25 mg, 0.044
mmol) in dichloromethane (25 mL), and the resulting mixture was
stirred in the dark for 10 h at room temperature. The solution was
washed with water and brine, back-extracting each time with
dichloromethane, and the organic solutions were evaporated under
reduced pressure. The residue was purified on a grade 3 basic alumina
column, eluting with 50:50 dichloromethane−hexanes. A green and a
purple fraction eluted initially, and the product then eluted as a second
purple fraction. This was further purified by chromatography on a
grade 3 alumina column, eluting with dichloromethane−hexanes.
Following evaporation of the solvent on a rotary evaporator and drying
in vacuo overnight, the dimethoxy derivative (9.0 mg, 0.014 mmol,
32%) was obtained as a dark solid: mp 155−157 °C, dec; UV−vis (1%
Et3N−CHCl3) λmax (relative intensities) 287 (1.00), 343 (0.60), 488
(0.33), 582 nm (0.35); 1H NMR (500 MHz, CDCl3): δ 1.06 (3H, t, J
= 7.6 Hz), 1.16 (3H, t, J = 7.6 Hz), 1.42 (9H, s), 2.07 (3H, s), 2.31
(3H, s), 2.50 (2H, q, J = 7.6 Hz), 2.59 (2H, q, J = 7.6 Hz), 3.47 (3H,
s), 3.48 (3H, s), 6.130 (1H, s), 6.133 (1H, s), 6.60 (1H, s), 6.87 (1H,
s), 7.03 (1H, s), 7.22 (1H, dt, J = 0.9, 7.5 Hz), 7.29−7.34 (3H, m),
7.63 (1H, d, J = 7.5 Hz), 7.74 (1H, d, J = 7.5 Hz), 8.12 (1H, d, J = 10.6
Hz), 8.42 (1H, d, J = 10.9 Hz), 8.65 (1H, s), 10.40 (1H, v br); 13C
NMR (CDCl3) δ 9.6, 9.8, 16.34, 16.38, 17.9, 18.3, 32.1, 38.7, 56.6,
57.5, 72.6, 115.4, 116.6, 119.4, 121.02, 121.04, 121.3, 125.2, 125.3,
126.8, 127.5, 128.2, 131.4, 131.9, 136.76, 136.84, 137.2, 139.1, 141.8,
148.0, 161.8; HRMS (ESI) calcd for C43H46N2O2 + H 623.3638, found
623.3634.
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23-tert-Butyl-5,20-diethoxy-13,17-diethyl-5,20-dihydro-
12,18-dimethyl-22-carbabenzo[g]azuliporphyrin (50b). Dicar-
baporphyrin 44b (25 mg, 0.044 mmol) was reacted with silver(I)
acetate (75 mg, 0.45 mmol) in dichloromethane (25 mL) and ethanol
(25 mL) using the conditions described above. The diethoxy derivative
(12 mg, 0.018 mmol, 41%) was isolated as a dark solid: mp 160−163
°C, dec; UV−vis (CHCl3) λmax (relative intensities) 288 (1.00), 341
1
(0.52), 403 (0.26), 501 (sh, 0.30), 556 nm (0.37); H NMR (500
MHz, CDCl3) δ 1.05 (3H, t, J = 7.6 Hz), 1.15 (3H, t, J = 7.6 Hz), 1.26
(3H, t, J = 7.0 Hz), 1.30 (3H, t, J = 7.0 Hz), 1.41 (9H, s), 2.07 (3H, s),
2.30 (3H, s), 2.49 (2H, q, J = 7.0 Hz), 2.58 (2H, q, J = 7.6 Hz), 3.57−
3.76 (4H, m), 6.231 (1H, s), 6.236 (1H, br s), 6.59 (1H, s), 6.82 (1H,
br s), 7.01 (1H, s), 7.21 (1H, dt, J = 0.9, 7.5 Hz), 7.27−7.34 (3H, m),
7.62 (1H, d, J = 7.6 Hz), 7.75 (1H, d, J = 7.4 Hz), 8.11 (1H, d, J = 10.5
Hz), 8.40 (1H, d, J = 10.8 Hz), 8.67 (1H, s), 10.76 (1H, v br); 13C
NMR (CDCl3) δ 9.6, 9.8, 15.8, 15.9, 16.36, 16.37, 17.9, 18.2, 32.1,
38.7, 64.3, 65.2, 71.0, 115.2, 116.5, 119.3, 120.9, 121.0, 121.1, 125.2,
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141.7, 148.0, 161.7; HRMS (ESI) calcd for C45H50N2O2 + H
651.3951, found 651.3956.
ASSOCIATED CONTENT
(11) (a) Lash, T. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2533−
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(c) El-Beck, J. A.; Lash, T. D. Org. Lett. 2006, 8, 5263−5266. (d) Lash,
■
S
* Supporting Information
1
1
Selected H NMR, H−1H COSY, HSQC, DEPT-135, 13C
NMR, MS, and UV−vis spectra are provided. This material is
available free of charge via the Internet at http://pubs.acs.org.
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̈
2381
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