Further observations on conformational and substituent effects in acid-catalyzed "3 + 1" cyclizations of tripyrranes with aromatic dialdehydes

Article abstract of DOI:10.1021/jo301945f

Tripyrranes with tert-butyl and phenyl substituents have been prepared and used to synthesize oxybenziporphyrins, oxypyriporphyrins, benzocarbaporphyrins, and azuliporphyrins with phenyl and tert-butyl substituents via a "3 + 1" methodology. The proton NM

Full text of DOI:10.1021/jo301945f

Article
pubs.acs.org/joc
Further Observations on Conformational and Substituent Effects in
Acid-Catalyzed “3 + 1” Cyclizations of Tripyrranes with Aromatic
Dialdehydes†
Timothy D. Lash* and Katrina M. Bergman
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, United States
R
S
* Related Paper * Supporting Information
ABSTRACT: Tripyrranes with tert-butyl and phenyl substituents have
been prepared and used to synthesize oxybenziporphyrins, oxy-
pyriporphyrins, benzocarbaporphyrins, and azuliporphyrins with phenyl
and tert-butyl substituents via a “3 + 1” methodology. The proton NMR
spectra for the tripyrrane dibenzyl esters indicate that these tripyrrolic
systems take on a helical conformation that favors macrocycle
formation, and the NMR data can be a useful predictor on the
efficiency of the “3 + 1” synthesis. Nevertheless, a tetraphenyltripyrrane
proved to be susceptible to acidolytic cleavage under the usual reaction conditions and gave poor yields of porphyrinoid
products. This problem could be overcome to a certain extent by carrying out the reactions in neat TFA. The presence of these
substituents led to significant changes in the spectroscopic properties and diatropic character of the new porphyrinoid structures.
Scheme 1
INTRODUCTION
■
The “3 + 1” variant of the MacDonald condensation,1 which
involves the acid-catalyzed reaction of a tripyrrane with an
aromatic dialdehyde, has proven to be a very valuable
methodology for synthesizing structurally diverse porphyrins2−5
and porphyrin analogue systems6−17 (Scheme 1). Commonly,
the tripyrrane (e.g., 1a), which consists of three pyrrole units
linked by single carbon bridges, is reacted with a dialdehyde in
the presence of trifluoroacetic acid.9,10 Following oxidation with
the electron-deficient quinone DDQ, or in some cases with
aqueous ferric chloride,15,16 porphyinoid products are com-
monly obtained in good to excellent yields. The versatility of
this approach has allowed the synthesis of many carbaporphyr-
inoid structures that incorporate benzene,9,10 azulene,12
indene,13 cyclopentadiene,13 cycloheptatriene,14 inverted pyr-
role units,15 and pyrazole rings.16 Nevertheless, the efficiency of
these cyclizations may be affected by the substituents attached
to the tripyrrane precursor, which in turn can alter the
conformation of this intermediate.18 Proton NMR spectroscopy
has been shown to give useful insights into the geometry of
tripyrrane structures. The proton NMR spectra of tripyrranes
with terminal benzyl ester groups (e.g., 1a) are unusual because
the ester methylene groups commonly show up at abnormally
high field values as broad singlets near 4.5 ppm, and the ortho-
protons of the associated phenyl groups are also shifted upfield
to 6.5−7.0 ppm.18 This compares to expectations that the
OCH2 resonance would give a sharp singlet at 5.2 ppm, while
the ortho-protons would be expected to show up at 7.2 ppm. In
addition, the bridging methylene units commonly give
broadened resonances, and further resolution can be observed
at lower temperatures.5a These observations suggest that
tripyrranes favor a helical geometry in solution that undergoes
an interconversion between the left-hand and right-hand helical
forms at a moderate rate on the NMR time scale.18 In this
conformation, the terminal benzyl esters overlie the π-system
Received: September 7, 2012
Published: October 2, 2012
© 2012 American Chemical Society
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on the opposite end of this tripyrrolic unit, and this leads to the
observed shielding effects. The helical conformation favors
porphyrinoid ring formation, and indeed these data suggest that
tripyrranes are predisposed for ring formation rather than
intermolecular condensations leading to oligomer or polymer
production. Tripyrranes with terminal tert-butyl ester units do
not show these effects in their NMR spectra,3,4 presumably due
to steric repulsion, but in the “3 + 1” methodology the esters
are cleaved and the deprotected tripyrrane can then take on the
necessary conformation for macrocycle formation.
Scheme 2
During the course of our studies into conjugated macrocycles
related to the porphyrins, we synthesized a tripyrrane 1b with
two tert-butyl substituents.18 The presence of compact
substituents such as tert-butyl or phenyl groups has been
shown to be beneficial in improving the solubility of the
porphyrinoid systems and may aid in the formation of X-ray
quality crystals for analysis.13b,19,20 However, it was noted that
the proton NMR spectrum for tripyrrane 1b in CDCl3 did not
show the features exhibited by tripyrrane 1a in that the benzyl
ester OCH2 units appeared as a sharp 4H singlet at 5.2 ppm,
the protons on the adjacent phenyl unit gave a multiplet at
7.2−7.3 ppm with no upfield resonance for the ortho-protons,
and the methylene bridges connecting the pyrrolic subunits
gave a sharp resonance at 3.5 ppm.18 These results strongly
imply that tripyrrane 1b does not favor a helical conformation.
The dibenzyl ester was deprotected with hydrogen over 10%
palladium−charcoal to give the related dicarboxylic acid 2b and
then further condensed with dialdehydes 3−5 under standard
conditions to give the related porphyrin analogues 6b, 7b, and
8b, respectively (Scheme 1).18 The yields for these syntheses
were all substandard compared to reactions using tripyrrane 1a.
Tripyrrane 1a has been reported to react with 5-formylsalicy-
laldehyde (3) in the presence of TFA in dichloromethane to
give, following oxidation with DDQ, oxybenziporphyrin 6a in
35−44% yield,9a,10 but reaction of 1b with 3 gave the related di-
tert-butyl porphyrinoid 6b in only 4.9% yield.18 Similarly, 1a
reacted with 3-hydroxy-2,6-pyridinedicarbaldehyde to give
oxypyriporphyrin 7a in 67% yield,11 while condensation of 1b
with 4 gave 7b in 25% yield.18 In addition, although tripyrrane
1a condensed with indene dialdehyde 5 to give benzocarba-
porphyrin 8a in 43% yield,13 reaction of 1b with 5 gave the
related carbaporphyrin 8b in only 18% yield.18 It was concluded
that the tert-butyl tripyrrane intermediate, like the dibenzyl
ester precursor 1b, does not favor the helical geometry that
facilitates macrocycle formation and that this is responsible for
the low yields. Furthermore, the proton NMR spectra for the
dibenzyl esters 1a and 1b appear to be useful predictors for the
efficiency of porphyrinoid macrocycle formation.18
give oxime 11, and this reacted with phenylacetone in the
presence of zinc dust and sodium acetate in acetic acid to give
the required pyrrole 9a in up to 50% yield. Transesterification
with benzyl alcohol containing a small amount of sodium
benzyloxide afforded the corresponding benzyl ester 9b, and
this was selectively oxidized with lead tetraacetate in acetic acid
to give the acetoxymethylpyrrole 12 (Scheme 2). Two
equivalents of 12 were condensed with 1 equiv of 3,4-
diethylpyrrole (13) under nitrogen in refluxing isopropyl
alcohol containing p-toluenesulfonic acid as a catalyst to give
tripyrrane 1c in 75% yield. As is often the case for tripyrrane
syntheses,2,23 the product precipitated out and could be isolated
in pure form by suction filtration. Tripyrrane 1d, which has two
phenyl and two tert-butyl substituents, was prepared similarly
by reacting 3,4-diphenylpyrrole (14) with acetoxymethylpyrrole
15 in refluxing acetic acid−isopropyl alcohol (Scheme 3). The
tripyrrane product could again be isolated by suction filtration
in 77% yield.
Scheme 3
In this study, tripyrranes with phenyl and tert-butyl
substituents have been further investigated, and useful trends
for porphyrinoid synthesis have been identified.
Tetraphenyltripyrrane 1c in CDCl3 gave a proton NMR
spectrum that was consistent with a helical conformation
(Figure 1a). The ortho-protons of the benzyl ester gave a
comparatively upfield resonance near 6.5 ppm, while the OCH2
units afforded two peaks near 4.0 and 4.8 ppm. The latter
resonances are not only shifted upfield but have resolved into
two separate peaks due to the diastereotopic nature of the
methylene protons. This reflects the chiral nature of the helical
conformation, which can only be interconverting relatively
slowly with the enantiomeric conformer on the NMR time
scale. The methylene protons for the bridges between the
pyrrolic subunits are also diastereotopic, giving rise to peaks at
3.6 and 4.0 ppm (the latter resonance overlaps with one of the
RESULTS AND DISCUSSION
■
In order to more efficiently introduce phenyl and/or tert-butyl
units into porphyrinoid structures, new tripyrranes were
targeted for study. A tetraphenyltripyrrane 1c was prepared in
three steps from 3,4-diphenylpyrrole ethyl ester 9a (Scheme 2).
The pyrrole precursor was prepared from ethyl benzoylacetate
(10) under Knorr condensation conditions. Although this
methodology dates back to the nineteenth century,21 the
conditions that we used to prepare 9a gave vastly improved
results compared to previous reports for this compound.22 Keto
ester 10 was nitrosated with sodium nitrite and acetic acid to
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Figure 1. 500 MHz proton NMR spectra of tetraphenyltripyrrane 1c. (A) NMR spectrum in CDCl3 at 25 °C showing relatively upfield
diastereotopic resonances for the benzyl ester CH2s between 4 and 5 ppm. The ortho-protons for the benzyl group are shifted upfield to 6.5 ppm,
and these data are consistent with the proposed helical geometry for tripyrranes in solution. The bridge methylenes are also highly diastereotopic,
showing peaks at 3.6 and 4.0 ppm. (B) NMR spectrum in DMSO-d6. The benzyl ester and bridge methylenes now give rise to two sharp 4H singlets
at 5.1 and 3.8 ppm, respectively, indicating that the tripyrrane no longer favors a helical conformation.
peaks for the benzyl ester methylene group; see Figure 1a).
Interestingly, when the spectrum for 1c is run in DMSO-d6,
these features are no longer seen. The benzyl ester OCH2 gave
a 4H singlet at 5.1 ppm, while the methylene bridges gave a
sharp singlet at 3.8 ppm. DMSO strongly hydrogen bonds with
pyrrolic NHs,24 and this undoubtedly leads to a disruption of
the helical structure. Hence, the conformation is solvent-
dependent, and the tripyrrane takes on an open structure in
DMSO. The proton NMR spectra for 1c are also temperature-
dependent (Figure 2). At 25 °C, the ester and bridge
methylenes are highly diastereotopic and the CH2 units for
the ethyl substituents give a broad peak at 2.2 ppm. At 40 °C,
the ethyl methylene resonance shows some fine structure while
the resonances for the OCH2 and bridge CH2 units have
broadened out. At 50 °C, the ethyl CH2 affords a recognizable
quartet, while the bridge CH2's gave a broad singlet, and the
ester methylenes produce a very broad peak centered on 4.6
ppm (Figure 2). As expected, these results demonstrate that
helix-to-helix interconversion occurs more rapidly at increased
temperatures.
Dibenzyl ester 1c was hydrogenolyzed over 10% Pd/C to
give the corresponding dicarboxylic acid 2c. As this system
favors a helical conformation in solution, it was anticipated that
1c would give good yields of porphyrinoid products using
MacDonald-type “3 + 1” condensations. However, this did not
prove to be the case. Reaction of 2c with 5-formylsalicylalde-
hyde in TFA−CH2Cl2, followed by oxidation with 1 equiv of
DDQ, gave oxybenziporphyrin in 14% yield (Scheme 4).
Attempts to react 2c with indene dialdehyde 5 gave even worse
results, and only trace amounts of impure benzocarbaporphyrin
8c could be isolated from these reactions. We noted that these
were messy reactions that resulted in the formation of tarry
materials and porphyrin byproducts. These results were
attributed to the tripyrrane being prone to acidolytic cleavage,10
a common problem for pyrrolic species of this type. Treatment
of 2c with TFA initially results in decarboxylation of the
terminal carboxylic acid groups to give 16 (Scheme 5). The
individual pyrrole units are prone to α-protonation to afford
cationic species such as 17, which can undergo a carbon−
carbon bond cleavage to give dipyrrylmethane 18 and cation
19. The latter species is resonance-stabilized as the azafulvene
structure 19′. Fragments 18 and 19 can recombine or further
react to give oligomeric or other macrocyclic products. Once
the porphyrinoid macrocycle has been generated, the product is
immune to these types of processes. However, the more
favorable the acidolytic cleavage process the faster it is likely to
occur, and this will compete with macrocycle formation. The
phenyl substituents in these structures are likely to stabilize the
azafulvene fragment by introducing canonical forms such as
19″. Hence, while the conformation of tripyrrane 16 is
conducive to the formation of the porphyrinoid ring, enhanced
acidolysis leads to the poor results that are observed. We
speculated that the cyclization reactions would occur more
rapidly in more concentrated solutions as the tripyrrane is
preorganized for cyclization and this would speed up the initial
condensation with the dialdehyde. With this in mind, tripyrrane
2c was condensed with 3 in neat TFA for 1 h, diluted with
dichloromethane, and oxidized with 0.1% aqueous ferric
chloride solution. Following purification by column chroma-
tography and recrystallization from chloroform−methanol,
oxybenziporphyrin 6c was isolated in 20% yield. Reaction of
2c with indene dialdehyde 5 under these conditions gave
benzocarbaporphyrin 8c in 8% yield (Scheme 4). Hence, this
concept appears to be valid, although the yields are relatively
low compared to most reactions of this type. Condensation of
2c with pyridine dialdehyde 4 in neat TFA gave oxy-
pyriporphyrin in 25% yield. Azulene dialdehyde 20 was also
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Figure 2. Partial 500 MHz proton NMR spectra of tetraphenyltripyrrane 1c in CDCl3 at 25, 35, 40, and 50 °C showing the region corresponding to
the ethyl (2.2 ppm), bridge (3.6−4.0 ppm), and benzyl ester (4.0−4.9 ppm) methylene resonances. As the temperature increases, the ethyl CH2
peak resolves as a quartet, while the diastereotopic protons for the bridging and benzyl ester methylenes are replaced by two broad peaks. These
results are consistent with an increased rate of interconversion between two enantiomeric helical conformations.
reacted with 2c under these conditions and afforded the
corresponding azuliporphyrin 21c in 15% yield.
99 mL CH2Cl2 for 16 h (dilute conditions), and 1 mL of TFA
in 19 mL CH2Cl2 for 2 h (concentrated conditions). All of the
“3 + 1” reactions conducted with tripyrrane 2d gave excellent
results. Reaction of 1d with 3 gave oxybenziporphyrin 6d in
52% yield under the more concentrated conditions and 62%
under the more dilute conditions. Condensation of 1d with 4
gave oxypyriporphyrin 7d in 80% yield under both sets of
conditions, while 5 reacted with 1d to give benzocarbaporphyr-
in 8d in 43% and 44% yields for the concentrated and dilute
conditions, respectively. Azulene dialdehyde 20 reacted with 2d
to give azuliporphyrin 21d in 59% and 65% yield, respectively.
Therefore, against expectations tripyrrane 2d is an exceptionally
good precursor for porphyrinoid synthesis. The difference
between tripyrranes 1b and 1d are relatively subtle, but it is
clear that the presence of two tert-butyl substituents in and of
itself does not inhibit macrocycle formation. There appears to
be a tipping point in terms of the favored conformation
between tripyrranes 1b and 1d, and only the latter structure
affords good yields of porphyrinoid products.
Tripyrrane 1d is structurally similar to 1b, both of which
possess two tert-butyl substituents. The apparent inhibition of
the helical conformer for 1b was attributed to the presence of
these bulky substituents, and the low yields for porphyrinoids
derived from 1b also appeared to be due to this factor. For this
reason, we had anticipated that tripyrrane 1d would give poor
results in “3 + 1” syntheses. However, the proton NMR
spectrum for 1d indicated that this tripyrrolic compound
actually favors the helical conformation. The proton NMR
spectrum for 1d in CDCl3 gave a broad singlet at 4.9 ppm for
the benzyl ester methylenes, while the ortho-protons gave a
slightly upfield resonance at 7.0 ppm. The bridging methylenes
also produced a broad singlet at 4.0 ppm. In DMSO-d6, the
spectrum showed the loss of this conformation, but this is
observed for all tripyrrane structures. Cleavage of the benzyl
esters by hydrogenolysis over 10% Pd/C gave the related
dicarboxylic acid 2d in quantitative yield. This was reacted with
dialdehydes 3−5 and 20 in the presence of TFA in
dichloromethane, followed by neutralization of the solution
with triethylamine and oxidation with 1 equiv of DDQ
(Scheme 4). Using 100 mg of tripyrrane 1d and 1 equiv of
dialdehyde, two sets of conditions were used: 1 mL of TFA and
The porphyrinoids obtained from tripyrrane 1d gave
spectroscopic properties comparable to those obtained from
1a, and oxybenziporphyrin 6d, oxypyriporphyrin 7d, benzo-
carbaporphyrin 8d, and azuliporphyrin 21d all showed UV−vis
spectra similar to those previously reported for 6a, 7a, 8a, and
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to the presence of a cross-conjugated azulene subunit.12
Nevertheless, these porphyrinoids do show a degree of
diatropic character, which has been rationalized as being due
to dipolar canonical forms such as 21′ that possess 18π electron
delocalization pathways (Scheme 6). The internal protons in
Scheme 4
Scheme 6
Scheme 5
21a cannot be identified with confidence due to the low
solubility of this compound,12 although the external meso-
protons were observed near 8.0 and 8.9 ppm for proton NMR
spectra of 21a in CDCl3. As the meso-protons for 21d appear as
two 2H singlets at 8.61 and 8.95 ppm, the data suggest that the
diatropicity has been slightly enhanced. Addition of TFA to
solutions of azuliporphyrins leads to the formation of the
corresponding dications 21H2 (Scheme 6).12 The NMR
2+
spectra for the diprotonated species show a more substantial
diamagnetic ring current due to the greater favorability of
2+
resonance contributors such as 21′H2 with 18π electron
delocalization pathways that aid in charge delocalization. The
2+
2+
NMR data for dications 21aH2 and 21dH2 showed similar
chemical shifts when the proximity to tert-butyl and phenyl
substituents was taken into account, indicating that the
aromatic character of these two species are similar. In contrast
to the observations for the “d series”, porphyrinoids derived
from tripyrrane 1c gave somewhat altered UV−vis spectra and
reduced diatropic character. The UV−vis spectra for the “c
series” all showed small bathochromic shifts in the Soret band
region and broadened absorptions for the Soret and Q bands.
Benzocarbaporphyrin 8d gave a Soret band at 432 nm, a
smaller peak at 386 nm, and Q absorptions at 521, 556, 604,
and 664 nm, but these peaks appeared at 434, 383, 517, 549,
616, and 677 nm, respectively, for 8c (Figure 3a). Oxy-
pyriporphyrin 7d gave a Soret band at 429 nm with a shoulder
at 442 nm and Q bands at 546, 592, and 614 nm, but these
21a where R1 = Me and R2 = R3 = Et. However, the proton
NMR spectra for the “d series” indicated that the diatropic
character had been slightly enhanced. For instance, the external
meso-protons for benzocarbaporphyrin 8a were reported to give
two 2H singlets at 9.82 and 10.10 ppm,13 whereas these
resonances appeared at 10.17 and 10.37 ppm for 8d. Even
taking into account proximity to tert-butyl or phenyl
substituents, the downfield shifts are significant. Azuliporphyr-
ins are often rather insoluble in organic solvents unless the
azulene ring has been substituted with a phenyl or tert-butyl
unit.19,20 However, 21d was reasonably soluble, and this
enabled the internal CH and NH resonances to be identified at
2.53 and 2.88 ppm, respectively. Azuliporphyrins do not exhibit
the very large diamagnetic ring currents seen for 6, 7, and 8 due
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Scheme 7
Figure 3. UV−vis spectra of selected porphyrinoids. (A) Comparison
of the UV−vis spectra of benzocarbaporphyrins 8c (red line) and 8d
in 1% Et3N−CHCl3. (B) Comparison of the UV−vis spectra of
oxypyriporphyrins 7c (red line) and 7d in 1% Et3N−CHCl3.
absorptions appeared at 432, 451, 546, 587, and 610 nm for 7c
(Figure 3b). Similarly, oxybenziporphyrin 1d gave Soret bands
at 436 and 456 nm and Q bands at 552, 596, 639, and 700 nm,
while 1c gave Soret bands at 438 and 465 nm and Q
absorptions at 545, 586, 639, and 709 nm. The electronic
absorption spectra for azuliporphyrins 21 were also noticeably
different, and 21d showed four absorptions in the Soret region
at 368, 404, 451, and 479 nm compared to values of 373, 392,
462, and 489 nm for 21c. The proton NMR spectra for the “c
series” oxybenziporphyrin 6c, oxypyriporphyrin 7c, and
benzocarbaporphyrin 8c all showed reduced diatropic character
compared to the “d series”, and the observed resonances gave
values that were closer to those obtained for the original “a
series” porphyrinoids. Nevertheless, the diatropicity appeared
to be higher for the “c series” compared to the “a series”,
particularly for oxybenziporphyrin 6c. The differences observed
for the “c series” are unlikely to be due to steric interactions,
and there is little reason to suppose that the planarity of these
macrocycles has been compromised. The changes are instead
attributed to conjugation with the four phenyl substituents.
Although these units cannot lie coplanar with the macrocycle,
there must be sufficient interactions to affect the UV−vis
spectra. This type of conjugation interaction can be represented
by dipolar canonical forms such as 22 (Scheme 7) that would
not possess the 18π electron delocalization pathway necessary
for porphyrinoid aromaticity, and this may be responsible for
the observed reduction in diatopic character compared to the
“d series”. Azuliporphyrin 21c proved to have excellent
solubility characteristics, and the proton NMR spectrum for
21c in CDCl3 showed the internal CH resonance as a sharp
singlet at 2.79 ppm and the NH as a broader peak at 2.65 ppm
(Figure 4). The meso-protons showed up as two 2H singlets at
8.35 and 9.16 ppm, while the azulene protons closest to the
Figure 4. Partial 500 MHz proton NMR spectrum of tetraphenyla-
zuliporphyrin 21c showing the internal CH and NH resonances and
the region corresponding to the external aromatic protons.
macrocycle gave rise to a doublet at 9.19 ppm. These results
indicate that 21c is at least as diatropic as 21d and has
significantly increased diatropicity compared to 21a. However,
2+
addition of TFA gave rise to a dication 21cH2 that had
2+
reduced diatropicity compared to 21aH2 or 21dH22+. In the
2+
proton NMR spectrum for 21cH2 in TFA−CDCl3, the
internal CH gave a resonance at −2.65 ppm compared to values
2+
2+
of −2.91 and −2.98 ppm for 21dH2 and 21aH2
,
2+
respectively. In addition, 21cH2 gave two 2H singlets for
the meso-protons at 9.60 and 10.39 ppm, compared to values of
10.08 and 10.47 ppm for 21dH22+ and 9.60 and 10.45 ppm for
12
2+
2+
21aH2
.
The small reduction in the diatropicity for 21cH22+
is attributed to resonance contributors such as 21c″H2
(Scheme 6) that do not possess 18π electron delocalization
pathways. In the free base form 21c, the favorability of aromatic
dipolar canonical forms such as 21′ (Scheme 6) may be
increased due to the reduced electron-donating character of
phenyl moieties compared to alkyl substituents, and this could
result in the slightly increased aromatic properties of this
species.
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°C over a 90 min period while periodically adding small portions of
the sodium benzyloxide solution. When the vapor temperature
reached 190 °C, the last 1 mL of the sodium benzyloxide solution
was added, and the reaction was allowed to continue for a further 5
min. The hot solution was poured into a chilled mixture of methanol
(100 mL), water (62 mL), and acetic acid (1 mL) while stirring with a
glass rod, and the resulting precipitate was collected by suction
filtration. Recrystallization from ethanol gave the benzyl ester (30.90 g,
CONCLUSIONS
■
The “3 + 1” variant on the MacDonald condensation remains
one of the most versatile routes to meso-unsubstituted
porphyrinoid systems. Good yields are often obtained, in part
due to the tripyrrane intermediates taking on a helical
conformation that makes them predisposed to macrocycle
formation. The presence of bulky substituents can disfavor the
helical conformer and may lead to reduced yields of
porphyrinoid products. However, this problem is rarely
observed and can be predicted by analyzing the proton NMR
spectra for the tripyrrane dibenzyl esters. A more challenging
problem arises when the tripyrrolic intermediates are prone to
acid-catalyzed cleavage, as this can greatly reduce the yields of
the targeted porphyrinoids. It was demonstrated that a
tetraphenyltripyrrane of this type that favors the helical
conformation gave improved yields when reacted with
dialdehydes in neat TFA, as this increased the rate of reaction
with the dialdehydes and dilute conditions were not required
due to the system being prearranged for cyclization. Although
the yields in this case were modest, porphyrinoids with
modified spectroscopic characteristics were identified.
1
84.2 mmol, 82%) as pale pink crystals, mp 176−177 °C; H NMR
(500 MHz, CDCl3) δ 2.34 (3H, s), 5.20 (2H, s), 7.00−7.03 (2H, m),
7.09−7.12 (2H, m), 7.13−7.17 (1H, m), 7.18−7.23 (7H, m), 7.26−
7.29 (3H, m), 9.15 (1H, br s); 13C NMR (CDCl3) δ 12.5, 65.9, 117.1,
124.6, 126.1, 126.8, 127.6, 128.03, 128.05, 128.1, 128.5, 130.4, 130.5,
131.0, 131.5, 134.7, 136.2, 161.2; EI MS m/z (% rel int) 367 (100,
M+), 259 (56, [M − BnOH]+), 233 (43). Anal. Calcd for C25H21NO2:
C, 81.72; H, 5.76; N, 3.81. Found: C, 81.79; H, 5.80; N, 4.03.
Benzyl 5-Acetoxymethyl-3,4-diphenylpyrrole-2-carboxylate
(12). Benzyl 5-methyl-3,4-diphenylpyrrole-2-carboxylate (1.00 g, 2.72
mmol) was gently warmed with acetic acid (32 mL) and acetic
anhydride (2 mL) until it was completely dissolved. Lead tetraacetate
(95%, 1.27 g, 2.72 mmol) was then added, and the mixture was stirred
at room temperature for 16 h. The mixture was poured into ice−water,
and the resulting precipitate was suction filtered, washed with water,
and dried in vacuo overnight. Recrystallization from chloroform−
hexanes yielded the acetoxymethylpyrrole (0.951 g, 2.23 mmol, 82%)
as a white solid, mp 187−188 °C; 1H NMR (500 MHz, CDCl3) δ 2.15
(3H, s), 5.05 (2H, s), 5.20 (2H, s), 7.03−7.06 (2H, m), 7.10−7.12
(2H, m), 7.15−7.24 (8H, m), 7.26−7.28 (3H, m), 9.55 (1H, br s); 13C
NMR (CDCl3) δ 21.2, 57.8, 66.1, 119.3, 126.8, 127.0, 127.4, 127.6,
127.7, 127.9, 128.0, 128.1, 128.3, 128.6, 130.4, 131.0, 133.4, 134.1,
136.0, 160.9, 172.2. Anal. Calcd for C27H23NO4: C, 76.22; H, 5.45; N,
3.29. Found: C, 76.55; H, 5.48; N, 3.52.
EXPERIMENTAL SECTION
■
Melting points are uncorrected. NMR spectra were recorded using a
400 or 500 MHz NMR spectrometer. Chemical shifts are reported in
parts per million (ppm) relative to CDCl3 (1H residual CHCl3 δ 7.26,
13C CDCl3 triplet δ 77.23) or DMSO-d6 (1H residual DMSO-d5 δ
2.49, 13C DMSO-d6 septet δ 39.7). H NMR values are reported as
1
chemical shifts δ, relative integral, multiplicity (s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet; br, broad peak) and coupling constant
(J). Coupling constants were taken directly from the spectra. 2D
experiments were performed by using standard software. High-
resolution mass spectra (HRMS) were determined by using a double
2,5-Bis(5-benzyloxycarbonyl-3,4-diphenyl-2-pyrrolylmeth-
yl)-3,4-diethylpyrrole (1c). 3,4-Diethylpyrrole25 (0.26 g, 2.11 mol)
and benzyl 5-acetoxymethyl-3,4-diphenylpyrrole-2-carboxylate18 (1.80
g, 4.23 mmol) were dissolved in 2-propanol (45 mL), p-
toluenesulfonic acid monohydrate (0.12 g) was added, and the
resulting mixture was stirred under reflux for 16 h. The solution was
allowed to cool to room temperature and further cooled in an ice bath.
The resulting precipitate was suction filtered, washed with 2-propanol,
and dried in vacuo overnight to give the tripyrrane dibenzyl ester (1.36
focusing magnetic sector instrument. H and 13C NMR spectra for all
1
new compounds are reported in Supporting Information.
Ethyl 5-Methyl-3,4-diphenylpyrrole-2-carboxylate (9a). A
solution of sodium nitrite (10.64 g) in water (16 mL) was added
dropwise to a stirred solution of ethyl benzoylacetate (22.2 mL, 24.6 g,
0.128 mol) in acetic acid while maintaining the temperature of the
reaction mixture below 15 °C with the aid of a salt−ice bath. The
resulting oxime solution was allowed to stir at room temperature
overnight. A solution of phenylacetone (17.25 g, 0.129 mol) in acetic
acid (80 mL) was heated to 70 °C. The previously prepared oxime
solution was added dropwise to the stirred mixture while
simultaneously adding a mixture of zinc dust (18 g) and sodium
acetate (36 g) in small portions, keeping the temperature of the
reaction mixture between 70 and 75 °C throughout. Following
completion of the addition, the stirred solution was heated at 120 °C
for 30 min. The mixture was cooled to 70 °C and poured into 1000
mL of ice−water. The resulting precipitate was suction filtered and
washed with water, followed by 2 × 100 mL of cold ethanol. The
product was vacuum-dried overnight to give the pyrrole ester (19.4 g,
63.6 mmol, 50%) as pale pink crystals, mp 169−170 °C (lit. mp22a 168
1
g, 1.59 mmol, 75%) as an off-white solid, mp 219 °C, dec; H NMR
(500 MHz, 25 °C, CDCl3) δ 0.85 (6H, t, J = 7.4 Hz), 2.19 (4H, br),
3.59 (2H, br), 4.02 (4H, br), 4.83 (2H, br), 6.43 (4H, br d, J = 7.0
Hz), 6.78−6.81 (4H, m), 6.97−7.03 (8H, m), 7.05−7.11 (12H, m),
7.18−7.22 (2H, m), 9.74 (1H, br s), 12.22 (2H, br s); 1H NMR (500
MHz, 50 °C, CDCl3) δ 0.87 (6H, t, J = 7.4 Hz), 2.20 (4H, q, J = 7.4
Hz), 3.82 (4H, br s), 4.66 (4H, v br), 6.49 (4H, br d, J = 7.0 Hz),
6.81−6.84 (4H, m), 6.99−7.04 (8H, m), 7.06−7.12 (12H, m), 7.16−
7.20 (2H, m), 9.58 (1H, br s), 12.01 (2H, br s); 1H NMR (500 MHz,
DMSO-d6) δ 0.63 (6H, t, J = 7.5 Hz), 1.85 (4H, q, J = 7.5 Hz), 3.79
(4H, s), 5.12 (4H, s), 6.87−6.89 (4H, m), 6.78−6.81 (4H, m), 7.05−
7.14 (20H, m), 7.23−7.26 (6H, m), 9.30 (1H, s), 11.73 (2H, s); 13C
NMR (CDCl3) δ 16.6, 17.7, 22.9, 66.0, 117.7, 119.7, 122.6, 124.5,
126.1, 126.4, 126.5, 127.2, 127.6, 128.02, 128.05, 130.4, 131.2, 131.4,
134.3, 134.4, 135.1, 135.9, 163.2; HR MS (FAB) calcd for C58H51N3O4
853.3879, found 853.3871. Anal. Calcd for C58H51N3O4: C, 81.57; H,
6.02; N, 4.92. Found: C, 81.60; H, 5.99; N, 5.10.
1
°C); H NMR (500 MHz, CDCl3) δ 1.16 (3H, t, J = 7.6 Hz), 2.35
(3H, s), 4.19 (2H, q, J = 7.6 Hz), 7.02−7.05 (2H, m), 7.14−7.17 (1H,
m), 7.19−7.23 (7H, m), 9.28 (1H, br s); 13C NMR (CDCl3) δ 12.5,
14.3, 60.2, 117.4, 124.3, 126.1, 126.7, 127.4, 128.1, 130.2, 130.5,
131.04, 131.10, 134,7, 134.9, 161.6; EI MS m/z (% rel int) 305 (78,
M+), 259 (100, [M − EtOH]+), 230 (26), 216 (27). Anal. Calcd for
C20H19NO2: C, 78.66; H, 6.27; N, 4.59. Found: C, 78.28; H, 6.29; N,
4.74.
2,5-Bis(5-benzyloxycarbonyl-3-tert-butyl-4-methyl-2-pyrro-
lylmethyl)-3,4-diphenylpyrrole (1d). 3,4-Diphenylpyrrole26 (0.48
g, 2.19 mmol) and benzyl 5-acetoxymethyl-4-tert-butyl-3-methylpyr-
role-2-carboxylate18 (1.50 g, 4.37 mmol) were dissolved in 2-propanol
(12.5 mL) and acetic acid (1.5 mL). The resulting solution was stirred
and refluxed under an atmosphere of nitrogen for 16 h. The mixture
was allowed to cool to room temperature and further cooled in an ice
bath. The resulting precipitate was filtered, washed with cold ethanol,
and dried in vacuo overnight to give the tripyrrane (1.34 g, 1.69 mmol,
Benzyl 5-Methyl-3,4-diphenylpyrrole-2-carboxylate (9b). A
solution of sodium benzyloxide was prepared by reacting sodium metal
(0.20 g) with benzyl alcohol (10 mL). A stirred solution of ethyl 3,4-
diphenylpyrrole-2-carboxylate (31.57 g, 0.103 mol) in benzyl alcohol
(40 mL) was gradually heated in a 250 mL Erlenmeyer flask on an oil
bath so that the temperature was raised from room temperature to 230
1
77%) as an off-white powder, mp 236−237 °C; H NMR (500 MHz,
25 °C, CDCl3) δ 1.04 (18H, br s), 2.49 (6H, s), 4.02 (4H, br s), 4.88
(4H, br s), 6.99−7.02 (4H, m), 7.13−7.24 (10H, m), 7.27−7.35 (6H,
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1
m), 8.89 (2H, v br), 11.29 (1H, v br); H NMR (500 MHz, 50 °C,
7−8 min. The two layers were separated, and the aqueous solution was
extracted with dichloromethane. The combined organic phases were
washed with water and 5% sodium bicarbonate solution and then
evaporated under reduced pressure. The residue was purified on a
grade 3 neutral alumina column, eluting with dichloromethane, and a
dark green product fraction was collected. The solvent was removed
on a rotary evaporator, and the residue was recrystallized from
chloroform−methanol to give the porphyrinoid product (20.4 mg,
0.0292 mmol, 20%) as purple crystals, mp 288−289 °C, dec.
CDCl3) δ 1.15 (18H, s), 2.49 (6H, s), 4.05 (4H, s), 5.04 (4H, br s),
7.01−7.04 (4H, m), 7.13−7.16 (2H, m), 7.18−7.22 (4H, m), 7.27−
7.34 (10H, m), 7.96 (1H, v br), 9.16 (2H, v br); 1H NMR (500 MHz,
DMSO-d6) δ 1.02 (18H, br s), 2.33 (6H, s), 4.06 (4H, s), 5.20 (4H, s),
6.96−6.98 (4H, m), 7.07−7.11 (2H, m), 7.16−7.20 (4H, m), 7.29−
7.33 (2H, m), 7.34−7.37 (4H, m), 7.38−7.41 (4H, m), 8.34 (1H, s),
10.62 (2H, s); 13C NMR (50 °C, CDCl3) δ 14.0, 26.7, 31.9, 33.1, 65.7,
118.4, 121.7, 124.9, 125.9, 127.8, 128.1, 128.2, 128.8, 129.6, 130.5,
135.9, 137.0, 161.7; 13C NMR (500 MHz, DMSO-d6) δ 13.4, 25.9,
31.2, 32.4, 64.5, 117.3, 119.4, 124.9, 125.3, 127.0, 127.95, 127.96,
127.98, 128.3, 128.5, 128.7, 129.7, 136.0, 136.9, 160.4; HR MS (ESI)
calcd for C52H55N3O4 + H 786.4271, found 786.4272. Anal. Calcd for
C52H55N3O4: C, 79.46; H, 7.05; N, 5.35. Found: C, 79.40; H, 7.08; N,
5.47.
13,14-Diethyl-8,9,18,19-tetraphenyl-2-oxybenziporphyrin
(6c). Method A. Tetraphenyltripyrrane dibenzyl ester 1c (0.600 g,
0.703 mmol) was placed in a hydrogenation vessel and dissolved in
freshly distilled THF (150 mL), methanol (50 mL), and triethylamine
(20 drops). After flushing the solution with nitrogen, 10% palladium
on activated carbon (100 mg) was added, and the resulting mixture
was shaken under hydrogen (40 psi) at room temperature overnight.
The catalyst was removed by suction filtration, and the solvent was
removed under reduced pressure. The residue was dissolved in 5%
aqueous ammonia (50 mL), and the solution was neutralized with
acetic acid to a litmus end point while maintaining the temperature at
0−5 °C using an ice−salt bath. The resulting precipitate was suction
filtered and washed repeatedly with water to remove all traces of acid.
After drying overnight in a vacuum desiccator, tripyrrane dicarboxylic
acid 2c (0.472 g, 0.701 mmol, quantitative) was obtained as a reddish
powder. This was used for porphyrinoid synthesis without further
13,14-Diethyl-8,9,18,19-tetraphenyl-2-oxypyriporphyrin
(7c). Using method B, 3-hydroxy-2,6-pyridinedicarbaldehyde11 (22.5
mg, 0.149 mmol) was reacted with tripyrrane 2c (100 mg, 0.148
mmol). Recrystallization from chloroform−methanol gave the oxy-
pyriporphyrin (26.2 mg, 0.0375 mmol, 25%) as purple crystals, mp
>300 °C; UV−vis (1% Et3N−CHCl3) λmax (log10 ε) 432 (5.28), 451
(5.09), 546 (4.09), 587 (4.25), 610 (4.10), 670 nm (3.55); UV−vis
(1% TFA−CHCl3) λmax (log10 ε) 433 (5.21), 456 (5.11), 550 (3.95),
594 (4.29), 646 (3.91), 720 nm (3.72); 1H NMR (500 MHz, CDCl3)
δ −2.92 (1H, br s), −2.75 (1H, br s), 1.75 (6H, t, J = 7.6 Hz), 3.74
(4H, q, J = 7.6 Hz), 7.62−7.73 (12H, m), 7.83−7.88 (1H, m), 7.94−
8.00 (8H, m), 9.20 (1H, br d, J = 9.5 Hz), 9.68 (1H, s), 9.89 (1H, s),
1
9.90 (1H, s), 10.98 (1H, s); H NMR (500 MHz, TFA−CDCl3) δ
−0.50 (2H, v br), 1.55−1.59 (6H, two overlapping triplets), 3.80−3.86
(4H, two overlapping quartets), 7.60−7.66 (12H, m), 7.67−7.73 (4H,
m), 7.75−7.78 (4H, m), 8.43 (1H, d, J = 9.7 Hz), 9.54 (1H, d, J = 9.7
Hz), 9.95 (1H, s), 10.314 (1H, s), 10.316 (1H, s), 10.90 (1H, s); 13C
NMR (CDCl3) δ 18.16, 18.19, 19.8, 100.1, 100.4, 107.1, 111.6, 128.2,
128.35, 128.38, 128.90, 128.93, 132.0, 132.71, 132.74, 132.8, 133.1,
134.4, 134.5, 134.7, 145.8, 146.4, 156.7, 185.7; 13C NMR (TFA−
CDCl3) δ 17.28, 17.33, 20.1, 103.8, 104.0, 105.1, 108.5, 110.8, 113.1,
115.4, 117.6, 129.56, 129.58, 129.85, 129.88, 129.94, 131.5, 131.6,
131.7, 132.39, 132.44, 132.5, 132.6, 133.0, 135.2, 136.3, 141.5, 141.8,
142.1, 142.6, 143.0, 143.4, 143.6, 144.0, 144.1, 145.3, 145.5, 179.8;
HRMS (EI) calcd for C49H38N4O 698.3045, found 698.3031.
1
purification. H NMR (500 MHz, DMSO-d6) δ 0.62 (6H, t, J = 7.4
Hz), 1.83 (4H, q, J = 7.4 Hz), 3.77 (4H, s), 6.87−6.90 (4H, m), 7.06−
7.15 (16H, m), 9.47 (1H, br s), 10.88 (2H, v br), 11.54 (2H, br s); 13C
NMR (500 MHz, DMSO-d6) δ 16.3, 16.8, 22.4, 118.0, 118.9, 122.3,
123.2, 125.8, 126.0, 127.1, 127.3, 127.8, 128.1, 129.3, 130.4, 130.9,
132.2, 135.0, 135.3, 162.3.
12,13-Diethyl-7,8,17,18-tetraphenyl-21-carbabenzo[b]-
porphyrin (8c). Using method B, indene dialdehyde 527 (25.6 mg,
0.149 mmol) was reacted with 2c (100 mg, 0.148 mmol).
Recrystallization from chloroform−methanol gave the benzocarbapor-
phyrin (8.5 mg, 0.012 mmol, 8.0%) as purple crystals, mp >300 °C;
UV−vis (1% Et3N−CHCl3) λmax (log10 ε) 383 (4.71), 434 (5.19), 453
(sh, 4.81), 517 (4.43), 549 (sh, 3.84), 616 (3.82), 677 nm (3.88);
UV−vis (1% TFA−CHCl3) λmax (log10 ε) 315 (4.51), 408 (4.87), 447
The foregoing tripyrrane dicarboxylic acid (101.4 mg, 0.150 mmol)
was dissolved in TFA (1 mL) and stirred under nitrogen for 5 min.
The solution was diluted with dichloromethane (99 mL), 5-
formylsalicylaldehyde (22.7 mg, 0.151 mmol) was added, and the
mixture was stirred for 16 h at room temperature in the dark under a
nitrogen atmosphere. The solution was neutralized by the dropwise
addition of triethylamine, DDQ (36.5 mg) was added, and the
resulting solution stirred for an additional 1 h. The solution was
washed with water, and the solvent was removed on a rotary
evaporator. The residue was purified by column chromatography on
grade 3 neutral alumina, eluting with dichloromethane. The product
was collected as a dark green band. Recrystallization from chloro-
form−methanol gave the oxybenziporphyrin (14.4 mg, 0.021 mmol,
14%) as shiny purple crystals, mp 288−290 °C, dec; UV−vis (1%
Et3N−CHCl3) λmax (log10 ε) 438 (5.21), 465 (5.02), 545 (4.03), 586
(4.21), 639 (3.77), 709 nm (3.55); UV−vis (1% TFA−CHCl3) λmax
(log10 ε) 328 (4.56), 440 (5.21), 479 (4.95), 563 (4.01), 613 (4.10),
1
(4.97), 483 (4.73), 560 (4.19), 626 nm (4.10); H NMR (500 MHz,
CDCl3) δ −6.25 (1H, s), −3.25 (2H, v br), 1.78 (6H, t, J = 7.7 Hz),
3.81 (4H, q, J = 7.7 Hz), 7.61−7.75 (14H, m), 8.03−8.06 (8H, m),
8.62−8.66 (2H, m), 9.90 (2H, s), 10.12 (2H, s); 13C NMR (CDCl3) δ
18.4, 20.0, 98.6, 102.3, 110.3, 120.9, 126.9, 127.9, 128.0, 128.89,
128.91, 132.7, 133.0, 134.6, 135.0, 135.2, 135.37, 135.44, 135.9, 137.8,
141.4, 145.1, 154.2; HRMS (EI) calcd for C53H41N3 719.3301, found
719.3308.
12,13-Diethyl-7,8,17,18-tetraphenylazuliporphyrin (21c).
Using method B, tripyrrane 2c (100 mg, 0.148 mmol) was reacted
with 1,3-azulenedicarbaldehyde28 (27.4 mg, 0.149 mmol). The product
was purified by column chromatography on basic grade 3 alumina,
eluting initially with chloroform and then with 1−2% methanol−
chloroform. Recrystallization from chloroform−hexanes gave then
with azuliporphyrin (16.6 mg, 0.0227 mmol, 15%) as dark purple
crystals, mp >300 °C, dec; UV−vis (1% Et3N−CHCl3) λmax (log10 ε)
373 (sh, 4.83), 392 (4.83), 462 (4.71), 489 (4.86), 668 nm (4.09);
UV−vis (1% TFA−CHCl3) λmax (log10 ε) 380 (4.92), 478 (5.00), 646
1
634 nm (4.14); H NMR (500 MHz, CDCl3) δ −5.86 (1H, br d, J =
2.0 Hz), 1.70 (6H, t, J = 7.6 Hz), 3.63−3.68 (4H, two overlapping
quartets), 7.37 (1H, d, J = 9.4 Hz), 7.59−7.70 (12H, m), 7.87−7.94
(8H, m), 8.66 (1H, dd, J = 2.2, 9.6 Hz), 9.45 (1H, s), 9.51 (1H, s),
9.59 (1H, s), 10.55 (1H, s); 13C NMR (CDCl3) δ 17.97, 18.05, 19.8,
96.8, 98.6, 110.0, 113.4, 115.5, 123.4, 127.6, 128.07, 128.14, 128.40,
128.45, 128.90, 128.92, 128.94, 130.8, 132.0, 132.49, 132.51, 132.8,
132.9, 134.0, 134.27, 134.33, 134.35, 134.6, 135.5, 136.3, 138.2, 140.0,
141.1, 143.1, 145.4, 145.9, 147.8, 155.8, 157.3, 188.1; HRMS (EI)
calcd for C50H39N3O 697.3093, found 697.3097. Anal. Calcd for
C50H39N3O·0.3CHCl3: C, 82.34; H, 5.39; N, 5.73. Found: C, 82.50; H,
4.99; N, 5.93.
1
nm (4.26); H NMR (500 MHz, CDCl3) δ 1.57 (6H, t, J = 7.6 Hz),
2.65 (1H, br s), 2.79 (1H, s), 3.39 (4H, q, J = 7.6 Hz), 7.44−7.48 (2H,
m), 7.50−7.61 (10H, m), 7.65 (2H, t, J = 9.5 Hz), 7.71−7.75 (5H, m),
7.77−7.80 (4H, m), 8.35 (2H, s), 9.16 (2H, s), 9.19 (2H, d, J = 9.6
Hz); 1H NMR (500 MHz, TFA−CDCl3) δ −2.65 (1H, s), −1.32 (2H,
v br), 1.63 (6H, t, J = 7.7 Hz), 3.72 (4H, q, J = 7.7 Hz), 7.66−7.75
(12H, m), 7.78−7.81 (4H, m), 7.85−7.88 (4H, m), 8.53 (1H, t, J = 9.5
Hz), 8.61 (2H, t, J = 9.5 Hz), 9.60 (2H, s), 9.86 (2H, d, J = 9.6 Hz),
10.39 (2H, s); 13C NMR (CDCl3) δ 16.8, 18.8, 95.7, 112.6, 126.8,
127.0, 128.2, 128.3, 131.5, 131.7, 133.2, 135.6, 135.88, 135.91, 136.3,
Method B. Tripyrrane 2c (100 mg) and 5-formylsalicylaldehyde
(22.4 mg, 0.149 mmol) were stirred with TFA (5 mL) for 1 h at room
temperature under nitrogen. The solution was diluted with dichloro-
methane and shaken with a 0.1% aqueous ferric chloride solution for
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140.2, 140.6, 141.6, 142.7, 146.3, 150.3, 153.4, 159.5; 13C NMR
(TFA−CDCl3) δ 16.8, 19.7, 98.2, 113.6, 124.4, 129.1, 129.5, 129.6,
129.9, 131.9, 132.0, 132.1, 132.2, 140.0, 140.7, 143.3, 145.1, 145.2,
145.5, 146.2, 146.7, 154.7; HRMS (ESI) calcd for C54H41N3 + H
732.3379, found 732.3378.
13C NMR (CDCl3) δ 14.9, 34.5, 36.4, 98.1, 103.0, 108.6, 120.6, 126.8,
127.3, 128.4, 132.2, 132.7, 134.5, 135.9, 136.1, 137.1, 141.8, 143.1,
144.7, 151.1; HRMS (EI) calcd for C47H45N3 651.3614, found
651.3621. Anal. Calcd for C47H45N3: C, 86.60; H, 6.96; N, 6.45.
Found: C, 86.52; H, 7.00; N, 6.30.
9,18-Di-tert-butyl-8,19-dimethyl-13,14-diphenyl-2-oxyben-
ziporphyrin (6d). Using method A, tripyrrane dicarboxylic acid 2d
(100 mg, 0.165 mmol) was condensed with 5-formylsalicylaldehyde
(24.8 mg, 0.165 mmol). Recrystallization from chloroform−methanol
gave oxybenziporphyrin 6d (64.5 mg, 0.102 mmol, 62%) as purple
crystals, mp >300 °C. When the reaction was performed on the same
scale with 1 mL of TFA and 19 mL of CH2Cl2 for 2 h, 54.2 mg of the
porphyrinoid product (0.0862 mmol, 52%) was obtained. UV−vis (1%
Et3N−CHCl3) λmax (log10 ε) 343 (4.43), 436 (5.29), 456 (4.94), 552
(3.86), 596 (4.44), 639 (3.94), 700 nm (3.75); UV−vis (1% TFA−
CHCl3) λmax (log10 ε) 333 (4.44), 442 (5.17), 475 (4.72), 620 (4.11),
704 nm (3.69); 1H NMR (500 MHz, CDCl3) δ −6.35 (1H, s), −2.80
(1H, br s), −2.65 (1H, br s), 2.11 (9H, s), 2.12 (9H, s), 3.69 (3H, s),
3.77 (3H, s), 7.44 (1H, d, J = 9.4 Hz), 7.56−7.60 (2H, m), 7.64−7.67
(4H, m), 7.89−7.92 (4H, m), 8.74 (1H, dd, J = 1.4, 9.4 Hz), 9.39 (1H,
s), 9.99 (1H, s), 10.07 (1H, s), 10.65 (1H, s); 13C NMR (CDCl3) δ
14.9, 15.1, 34.3, 34.4, 36.14, 36.16, 101.1, 103.0, 105.6, 111.2, 111.9,
122.3, 126.7, 127.7, 128.5, 130.4, 132.3, 132.7, 134.9, 135.4, 136.1,
137.8, 138.9, 140.8, 142.0, 142.6, 145.2, 145.7, 148.1, 153.5, 154.9,
188.4; HRMS (EI) calcd for C44H43N3O 629.3406, found 629.3394.
Anal. Calcd for C44H43N3O: C, 83.91; H, 6.88; N, 6.67. Found: C,
83.51; H, 6.83; N, 6.65.
8,17-Di-tert-butyl-7,18-dimethyl-12,13-diphenylazulipor-
phyrin (21d). 1,3-Azulenedicarbaldehyde28 (29.6 mmol, 0.165 mmol)
was reacted with tripyrrane 2d (100 mg, 0.165 mmol) using the
foregoing procedure. The product was purified by column
chromatography on basic grade 3 alumina, eluting initially with
chloroform and then with 1−2% methanol−chloroform. Recrystalliza-
tion from chloroform−hexanes gave diphenylazuliporphyrin 21d (71.2
mg, 0.07 mmol, 65%) as dark green crystals, mp >300 °C. When the
reaction was performed on the same scale with 1 mL of TFA and 19
mL of CH2Cl2 for 2 h, 64.9 mg of product (0.0979 mmol, 59%) was
obtained. UV−vis (1% Et3N−CHCl3) λmax (log10 ε) 368 (4.79), 404
(4.75), 451 (4.73), 479 (4.80), 640 nm (4.17); UV−vis (1% TFA−
1
CHCl3) λmax (log10 ε) 374 (4.89), 476 (5.01), 655 nm (4.36); H
NMR (500 MHz, CDCl3) δ 1.85 (18H, s), 2.53 (1H, br s), 2.88 (1H,
br s), 3.21 (6H, s), 7.42 (2H, t, J = 9.5 Hz), 7.48−7.52 (3H, m), 7.53−
7.57 (4H, m), 7.73−7.75 (4H, m), 8.61 (2H, s), 8.95 (2H, s), 9.08
(2H, d, J = 9.5 Hz); 1H NMR (500 MHz, TFA−CDCl3) δ −2.91 (1H,
s), −1.60 (1H, v br), −0.72 (2H, s), 2.02 (18H, s), 3.67 (6H, s), 7.68−
7.72 (6H, m), 7.76−7.79 (4H, m), 8.57 (1H, t, J = 9.6 Hz), 8.68 (2H,
t, J = 9.7 Hz), 10.04 (2H, d, J = 9.6 Hz), 10.08 (2H, s), 10.47 (2H, s);
13C NMR (50 °C, CDCl3) δ 13.9, 33.9, 34.9, 100.9, 107.8, 126.5,
127.9, 128.4, 131.8, 132.1, 134.87, 134.94, 138.1, 140.0, 146.6, 149.0,
155.7, 162.8; 13C NMR (TFA−CDCl3) δ 14.9, 33.3, 36.4, 101.3,
109.6, 122.8, 125.2, 128.4, 129.6, 130.0, 131.8, 131.9, 140.7, 141.8,
142.1, 143.0, 143.09, 143.12, 146.86, 146.90, 147.6, 154.4; HRMS
(ESI) calcd for C48H45N3 + H 664.3692, found 664.3692. Anal. Calcd
for C48H45N3·1/3H2O: C, 86.06; H, 6.87; N, 6.27. Found: C, 85.98; H,
6.88; N, 6.27.
9,18-Di-tert-butyl-8,19-dimethyl-13,14-diphenyl-2-oxypyri-
porphyrin (7d). Using method A, dialdehyde 411 (25.0 mg, 0.165
mmol) was reacted with tripyrrane 2d (100 mg, 0.165 mmol).
Recrystallization from chloroform−methanol gave the diphenylox-
ypyriporphyrin (83.2 mg, 0.132 mmol, 80%) as lustrous purple
crystals, mp >300 °C. When the reaction was performed on the same
scale with 1 mL of TFA and 19 mL of CH2Cl2 for 2 h, 83.5 mg of
product (0.132 mmol, 80%) was obtained. UV−vis (1% Et3N−
CHCl3) λmax (log10 ε) 403 (infl, 4.75), 429 (5.40), 442 (sh, 5.11), 546
(3.82), 592 (4.37), 614 nm (4.50); UV−vis (1% TFA−CHCl3) λmax
(log10 ε) 430 (5.25), 445 (5.09), 548 (3.88), 598 (4.41), 627 (sh,
ASSOCIATED CONTENT
■
S
* Supporting Information
Selected 1H NMR, 1H−1H COSY, HMQC, 13C NMR, MS, and
UV−vis spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
4.22), 702 nm (4.02); H NMR (500 MHz, CDCl3) δ −3.15 (1H, br
s), −3.05 (1H, br s), 2.192 (9H, s), 2.195 (9H, s), 3.81 (3H, s), 3.89
(3H, s), 7.58−7.62 (2H, m), 7.68 (4H, t, J = 7.5 Hz), 7.92−7.96 (5H,
m), 9.31 (1H, d, J = 9.4 Hz), 9.63 (1H, s), 10.37 (1H, s), 10.38 (1H,
s), 11.09 (1H, s); 1H NMR (500 MHz, TFA−CDCl3) δ −1.23 (1H, br
s), −1.10 (1H, br s), 2.064 (9H, s), 2.067 (9H, s), 3.63 (3H, s), 3.68
(3H, s), 7.70−7.75 (6H, m), 7.77−7.81 (4H, m), 8.63 (1H, d, J = 9.6
Hz), 9.76 (1H, d, J = 9.6 Hz), 10.08 (1H, s), 10.81 (1H, s), 10.83 (1H,
s), 11.01 (1H, s); 13C NMR (CDCl3) δ 14.9, 15.2, 34.7, 36.41, 36.43,
103.2, 103.5, 104.0, 107.7, 127.7, 128.6, 131.7, 132.4, 134.5, 134.9,
136.0, 136.4, 137.0, 138.8, 139.5, 144.4, 144.8, 145.0, 145.2, 145.3,
146.8, 153.2, 153.6, 186.1; 13C NMR (TFA−CDCl3) δ 14.9, 15.2,
33.3, 36.40, 36.43, 101.2, 104.9, 106.1, 106.4, 129.41, 129.45, 129.8,
131.24, 131.28, 131.8, 131.9, 134.2, 135.1, 138.6, 139.8, 141.8, 142.0,
142.4, 142.5, 143.3, 144.2, 144.6, 144.9, 148.5, 148.8, 179.8; HRMS
(EI) calcd for C43H42N4O 630.3358, found 630.3343. Anal. Calcd for
C43H42N4O: C, 81.87; H, 6.71; N, 8.88. Found: C, 82.15; H, 6.78; N,
8.79.
R
* Related Articles
Part 63 in the series “Conjugated Macrocycles Related to the
Porphyrins”. For part 62, see: Lash, T. D.; Lammer, A. D.;
Ferrence, G. M. Angew. Chem., Int. Ed. 2012, in press; DOI:
10.1002/anie.201206385.
AUTHOR INFORMATION
Corresponding Author
*E-mail: tdlash@ilstu.edu.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
under grant nos. CHE-0911699 and CHE-1212691 and by the
Petroleum Research Fund, administered by the American
Chemical Society.
8,17-Di-tert-butyl-7,18-dimethyl-12,13-diphenyl-21-
carbabenzo[b]porphyrin (8d). Using method A, tripyrrane 2d (100
mg, 0.165 mmol) was reacted with indene dialdehyde 527 (28.5 mg,
0.165 mmol). Recrystallization from chloroform−methanol gave the
diphenylcarbaporphyrin (48.9 mg, 44%) as purple crystals, mp >300
°C. When the reaction was performed on the same scale with 1 mL of
TFA and 19 mL of CH2Cl2 for 2 h, 46.3 mg of product (0.0711 mmol,
43%) was obtained. UV−vis (1% Et3N−CHCl3) λmax (log10 ε) 386
(4.61), 432 (5.32), 521 (4.21), 556 (4.19), 604 (3.87), 664 nm (3.31);
UV−vis (1% TFA−CHCl3) λmax (log10 ε) 315 (4.44), 404 (sh, 4.74),
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