Synthesis of a series of aromatic benziporphyrins and heteroanalogues via tripyrrane-like intermediates derived from resorcinol and 2-methylresorcinol

Article abstract of DOI:10.1021/jo201098c

Tripyrrane analogues were prepared by reacting resorcinol or 2-methylresorcinol with 2 equiv of an acetoxymethylpyrrole in the presence of p-toluenesulfonic acid and calcium chloride. Following removal of the benzyl ester protective groups, the resorcinol

Full text of DOI:10.1021/jo201098c

ARTICLE
pubs.acs.org/joc
Synthesis of a Series of Aromatic Benziporphyrins and
Heteroanalogues via Tripyrrane-Like Intermediates Derived from
Resorcinol and 2-Methylresorcinol†
Timothy D. Lash,* Kae Miyake, Linlin Xu, and Gregory M. Ferrence
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, United States
S Supporting Information
b
ABSTRACT: Tripyrrane analogues were prepared by reacting
resorcinol or 2-methylresorcinol with 2 equiv of an acetoxy-
methylpyrrole in the presence of p-toluenesulfonic acid and
calcium chloride. Following removal of the benzyl ester pro-
tective groups, the resorcinol-derived benzitripyrrane was re-
acted with a pyrrole dialdehyde to give an aromatic hydroxy-
oxybenziporphyrin. However, furan and thiophene dialdehydes
gave highly insoluble products that could not be fully character-
ized. The methylresorcinol-derived tripyrrane analogue reacted with pyrrole, furan, thiophene, and selenophene dialdehydes to give
unstable porphyrinoids that were further oxidized with [bis(trifluoroacetoxy)iodo]benzene to give stable benziporphyrin
derivatives. These oxidized benziporphyrins showed strongly diatropic properties by proton NMR spectroscopy where the
differences in chemical shifts (Δδ) were >18 ppm in some cases. The selenophene-derived system was further characterized by
X-ray crystallography, and these results showed that one of the pyrrole subunits in this crowded structure was tilted by 21° relative to
the mean macrocyclic plane. The tripyrrolic system reacted with silver(I) acetate to give the corresponding silver(III)
organometallic complex. Regioselective alkylation with methyl or ethyl iodide and potassium carbonate gave diastereomeric
mixtures of N-alkyl derivatives, and the N-ethyl substitution products showed highly diastereotopic characteristics.
’ INTRODUCTION
optimal interactions between the oxygen lone pair electrons and
the π-system.10ꢀ12
Benziporphyrins are porphyrin analogues with a benzene ring
in place of one of the usual pyrrolic subunits.1ꢀ4 These systems
have been widely studied and show a diversity of spectroscopic
and chemical properties.1ꢀ9 Although simple benziporphyrins
like 1 and 2 are nonaromatic,1ꢀ3,5,6 substituted benziporphyrins
vary considerably and may be moderately10ꢀ12 or strongly
diatropic.2,3,13ꢀ17
Dimethoxybenziporphyrins 3a and 4a show significant diatropic
character because of the electron-donating properties of the
methoxy substituents which introduce dipolar canonical forms
like 30 and 40 that possess porphyrin-like 18π electron delocaliza-
tion pathways.10ꢀ12 The internal CH (22-H) gives rise to
relatively upfield resonances at 5.07 and 5.84 ppm for 3a and
4a, respectively. This effect is much reduced for 3-methylbenzi-
porphyrins 3b and 4b because the alkyl substituent prevents the
methoxy unit from taking on the correct geometry to allow
However, addition of TFA affords the related dications which
show dramatically increased diatropicity. For instance, 3aH2
2+
Received: May 27, 2011
Published: June 21, 2011
r
2011 American Chemical Society
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Scheme 1
Scheme 3
Scheme 2
Figure 1. Favored sites for electrophilic substitution in pyrrole, azulene,
and resorcinol.
of an alternative and more general route to this type of highly
aromatic porphyrinoid. In other work, we had shown that azulenes
11 reacted with acetoxymethylpyrroles 12 in the presence of acetic
acid to generate tripyrrane analogues 13 (Scheme 3).18ꢀ20 Cleavage
of the tert-butyl ester protective groups with TFA, followed by a “3 +
1” reaction with pyrrole dialdehyde 14a and oxidation with DDQ
afforded azuliporphyrins 15a.18ꢀ21 Heteroanalogues 15b and 15c
were prepared similarly from thiophene and selenophene dialde-
hydes 14b and 14c.18,19 In most porphyrin syntheses, the formation
of oligopyrrolic intermediates and the macrocycles themselves relies
on favorable electrophilic substitution at the R-positions on the
pyrrole nucleus. The formation of azulitripyrranes 13 relies upon
azulene’s ability to undergo preferential electrophilic substitution at
the structurally equivalent 1,3-positions (Figure 1),18ꢀ20,22ꢀ24 and
in this respect, azulene acts as a substitute for pyrrole in this
chemistry. As resorcinol (16a) and 2-methylresorcinol (16b) also
favor electrophilic substitution at the analogous 4,6-positions
(Figure 1), we speculated that these dihydroxybenzenes could be
used to prepare tripyrrane analogues as well. These benzitripyrranes
(17) would in turn be potential intermediates for “3 + 1” MacDonald
syntheses25,26 of modified benziporphyrins like 10.27 The suc-
cessful application of this strategy to the synthesis of benzipor-
phyrin analogues is presented below.
showed the 22-H upfield at ꢀ0.68 ppm, and even the 2-methyl
2+
analogue 3bH2 gave the 22-H resonance at a comparatively
upfield value of 2.8 ppm.10 In an early study, we speculated that
2-hydroxybenziporphrin 5 would tautomerize to give a fully aro-
matic system 6 with both a thermodynamically favorable carbonyl
unit and a porphyrin-like delocalization pathway.2 Reaction of
4-hydroxy-1,3-benzenedicarbaldehyde with tripyrrane 7 did indeed
afford the aromatic carbaporphyrinoid 6, named oxybenziporphyrin,
and in this case, the internal CH was shifted to ꢀ7.2 ppm
Scheme 1).2,3 Treatment of dimethoxybenziporphyrins 3 with
BBr3 gave the methoxyoxybenziporphyrins 8, while reaction of 3a
with refluxing HBr in acetic acid afforded a highly insoluble
hydroxyoxybenziporphyrin 9 (Scheme 2).10 However, cleavage of
the methyl ethers in 3b with refluxing HBr in acetic acid occurred
with concomitant oxidation to afford the highly unusual benzipor-
phyrin derivative 10.10 This system showed strikingly diatropic
characteristics, and its proton NMR spectrum afforded a resonance
for the 22-H at ꢀ8.52 ppm, while the external meso-protons gave
rise to two 2H singlets at 9.39 and 10.19 ppm.10 Given the unusual
characteristics of this system, we were interested in the development
’ RESULTS AND DISCUSSION
Azulitripyrrane 13a was prepared by reacting azulene and
acetoxymethylpyrrole 12 in refluxing acetic acid and isopropyl
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Scheme 4
Scheme 5
alcohol (Scheme 3),18 and we initially anticipated that resorcinol
could be reacted under the same conditions. However, when 16a
was reacted with 2 equiv of acetoxymethylpyrrole 18, none of the
targeted benzitripyrrane 17a was formed (Scheme 4). Trace
amounts of the desired product were identified when the reaction
was carried out in refluxing acetic acid and ethanol. A problem
that arises in this chemistry is that competing reactions can occur,
specifically self-condensation of pyrrole 18 to give a dipyrryl-
methane 19 and solvolysis reactions that can afford ether
derivatives. In order to obtain practical yields of benzitripyrrane,
electrophilic substitution of resorcinol must occur more rapidly
than these competing processes. A series of experiments were
conducted to optimize the reaction of resorcinol with 18.
Reaction of 16a and 18 in acetic acid with Montmorillonite
clay28 gave 17a in 6% yield. Montmorillonite clay gave better
results in diethyl ether and generated 17a in 15% yield. In
dichloromethane, the yield was raised to 17%. Other types of
acid catalysts were investigated, including Florisil, HBr, and
methanesulfonic acid, but these all gave inferior results. As
phenoxide ions are more reactive toward electrophiic substitu-
tion than phenols, reactions were attempted using basic condi-
tions with sodium hydroxide, DBU, or DMAP, but only trace
amounts of the benzitripyrrane product was formed. p-Toluene-
sulfonic acid in dichloromethane gave modest results (12%
yield), but addition of calcium chloride with this acid catalyst
raised the yield to 24% (Scheme 4). The role of the calcium
chloride is unclear. It may act by absorbing trace amounts of
water or as a cocatalyst. By itself, calcium chloride was not a useful
catalyst. Reaction of 16a and 18 in the presence of p-toluene-
sulfonic acid with other inorganic salts such as magnesium
sulfate, sodium sulfate, or sodium chloride showed no improve-
ment in the yields over using the acid catalyst alone. Self-
condensation of the acetoxymethylpyrrole 18 to form dipyrryl-
methane 19 was the main side reaction under these conditions. In
an attempt to minimize this side reaction, a solution of 18 in
dichloromethane was added over a 10 h period via a syringe
pump to a stirred mixture of resorcinol, p-toluenesulfonic acid,
and calcium chloride in dichloromethane. This modification gave
the best results, and following chromatography on a silica
column, benzitripyrrane 17 was isolated in 33% yield. The
product fractions were identified by TLC. On the plate, the
dipyrrylmethane byproduct turned red in the presence of bro-
mine vapor,29,30 but the benzitripyrrane gave a characteristic blue
color.30 Recrystallization from chloroformꢀhexanes gave 17 as
white crystals. Under the same conditions, methylresorcinol 16b
was reacted with 2 equiv of acetoxymethylpyrrole 18, and the
related benzitripyrrane was isolated in 30% yield. Again, the
product was purified by column chromatography on silica, and
the product fractions were identified by TLC. The tripyrrane
analogue showed up as a dark green spot on the TLC plate in the
presence of bromine vapor.
The benzitripyrranes were generated with terminal benzyl
ester protective groups, and these were easily cleaved to give the
corresponding dicarboxylic acids 20 in near-quantitative yields
by treating 17 with hydrogen over 10% palladiumꢀcharcoal.
Benzitripyrrane dicarboxylic acid 20a was reacted with pyrrole
dialdehyde 14a31 in the presence of TFA in dichloromethane for
16 h (Scheme 5). Following oxidation with dilute aqueous ferric
chloride solution,32 purification by flash chromatography on
silica and recrystallization from chloroformꢀhexanes, hydro-
xyoxybenziporphyrin 21 was isolated in 37% yield. The UVꢀvis
spectrum for 21 in 2% triethylamineꢀchloroform was very
porphyrin-like with a strong Soret band at 422 nm, followed by
four smaller Q bands at 528, 570, 620, and 684 nm (Figure 2).
However, the free base in deacidified chloroform gave a very poor
quality spectrum with a Soret band at 425 nm because of its very
low solubility in this solvent (Figure 2). The spectrum in
Et3NꢀCHCl3 was attributed to the formation of an anionic
species (Figure 3). The UVꢀvis spectrum in 2% DBUꢀCHCl3
was quite different, showing a broad Soret band at 409 nm as well
as Q bands at 519, 559, 616, and 678 nm (see the Supporting
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Scheme 6
Figure 2. UVꢀvis spectra of hydroxyoxybenziporphyrin 21. Free base
in deacidified chloroform (purple line); monocation 21H+ in CHCl3
2+
with 3 equiv of TFA (blue line); dication 21H2 in CHCl3 with 200
equiv of TFA (green line); monoanion in 2% Et3NꢀCHCl3 (red line).
TFA and could not be characterized by NMR spectroscopy.
High-resolution mass spectrometry confirmed that 22a and 22b
had been generated, but it was not possible to obtain any further
characterization or to determine the purity of the isolated
materials.
Figure 3. Monoanion formed by adding triethylamine to a solution of
21 in chloroform.
Information), and this may be due to further deprotonation of
the system. Titration of a solution of 21 in chloroform with TFA
initially generated a monocation 21H+ (Scheme 5), and this
showed a split Soret band at 410 and 427 nm (Figure 2).
Monoprotonation was complete following the addition of 3
equiv of TFA, but further addition of acid generated the dication
Benzitripyrrane 20b reacted with pyrrole dialdehyde 14a
under the same conditions, and following column chromatogra-
phy and recrystallization, hydroxyoxybenziporphyrin 23 was
isolated as the major product in 27% yield (Scheme 6). The
further oxidized derivative 24 was observed as a minor byproduct
(5%). Porphyrinoid 23 gave a porphyrin-like UV spectrum with a
Soret band at 424 nm. The free base was again poorly soluble in
2+
21H2 (Scheme 5). The system was fully diprotonated in the
presence of 200 equiv of TFA. The dication gave a Soret band at
429 nm and Q bands at 555, 601, 653, and 717 nm. Further
addition of TFA resulted in minor changes in the UVꢀvis
spectrum (see the Supporting Information). As porphyrinoid
21 is poorly soluble in organic solvents and the free base could
not be characterized by proton NMR spectroscopy. However,
the dication in TFAꢀCDCl3 gave a well-resolved proton NMR
spectrum that showed the internal CH at ꢀ2.35 ppm and a broad
NH near ꢀ0.8 ppm. The external meso-protons gave two 2H
singlets at 8.89 and 10.10 ppm. The methyl substituents, which
are strongly deshielded in true porphyrins to 3.6 ppm, showed up
as a 6H singlet at 3.11 ppm. These data confirm that the dication
is strongly diatropic, although the diatropicity is somewhat
reduced compared to porphyrins33 or the free base form of
oxybenziporphyrin 6.2 These results are in line with those
previously obtained for the isomer 9 and related methoxybenzi-
porphyrins 8.10 Benzitripyrrane 20a was also reacted with
thiophene dialdehyde 14b and furan dialdehyde 14d in an
attempt to prepare the heterobenziporphyrins 22. The UVꢀvis
spectra for these products were porphyrin-like and showed Soret
bands near 400 nm. Unfortunately, these compounds were
extremely insoluble in organic solvents even in the presence of
2+
chloroform, but the dication 23H2 formed upon addition of
TFA gave a good quality proton NMR spectrum where the
internal CH gave an upfield resonance at ꢀ1.14 ppm, while the
meso-protons appeared downfield at 8.54 and 9.72 ppm. The
diamagnetic ring current for 23H22+ is slightly reduced compared
to 21H22+. The hydroxyl group helps to stabilize the positive
charges without disrupting the 18π electron delocalization path-
way that is responsible for the macrocycles aromatic properties
(Scheme 7). The protonated form of oxybenziporphyrin (6H22+
)
shows a much greater decrease in diatropicity because of cross-
conjugated phenolic canonical forms like 25, and its proton
NMR spectrum in TFAꢀCDCl3 shows the 22-H at 1.5 ppm.3a
The hydroxyl group in 23H22+ is less effective at stabilizing the
positive charges compared to 21H22+ because of steric crowding
by the methyl group, which disrupts conjugation in this portion
of the molecule.
Isolation of pure 23 proved to be difficult because of its poor
stability. In part, this was due to air oxidation to 24, but this
process was not very efficient. Significant conversion occurred
when chloroform solutions of 23 were stirred open to the air for
several days. However, only poor yields of 24 could be isolated.
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Scheme 7
Figure 4. UVꢀvis spectra of oxidized benziporphyrin 24. Free base in
1% Et3NꢀCHCl3 (red line). Cation 24H+ in 1% TFAꢀCHCl3 (blue
line).
Scheme 8
proton NMR spectrum for 26 in CDCl3 showed the internal CH
at ꢀ7.45 ppm, while the exterior meso-protons gave rise to two
2H singlets at 9.72 and 10.58 ppm. The carbon-13 NMR
spectrum for 26 confirmed the presence of a plane of symmetry
for the macrocycle and showed a carbonyl resonance at
194.5 ppm.
As bromine addition to 23 occurs readily, we speculated that a
similar electrophilic addition could give superior yields of
porphyrinoid 24. This was accomplished by reacting 23 with
the hypervalent iodine reagent [bis(trifluoroacetoxy)iodo]-
benzene (27, Scheme 8). Reaction of crude 23 with 27 in acetic
acid gave slightly improved yields compared to the ferric chloride
oxidation, but these yields remained disappointing. However,
when the reaction was carried out in a mixture of dichloro-
methane and methanol in the presence of potassium carbonate,
the oxidized benziporphyrin could be isolated as red crystals in an
overall yield of 24% from benzitripyrrane 20b. As expected, 24
gave a porphyrin-like UVꢀvis spectrum with broad Soret band at
417 nm and a series of Q bands in the visible region (Figure 4).
Addition of TFA gave the corresponding cation 24H+ with a split
Soret band at 413 and 427 nm (Figure 4). In fact, the spectro-
scopic properties for 24 and bromo derivative 26 are quite
similar, which is hardly surprising given that they essentially
share the same chromophore. The IR spectrum of 24 gave rise to
two strong absorption bands at 1661 and 1699 cmꢀ1 caused by
the antisymmetrical and symmetrical stretching modes for the
two carbonyl groups. The proton NMR spectrum for 24 in
CDCl3 showed the internal CH at ꢀ8.0 ppm (as is the case for all
of these porphyrin analogues, the chemical shifts varied to a small
extent with concentration), while the meso-protons appeared
downfield as two 2H singlets at 9.50 and 10.31 ppm (Figure 5).
The methyl groups gave a 6H singlet at 3.53 ppm, confirming the
highly diatropic nature of porphyrinoid 24. The methylene
protons for the ethyl substituents are diastereotopic even though
24 has a plane of symmetry and is achiral. This is due to the two
methylene protons residing in different environments relative to
the tertiary alcohol unit. Figure 6 shows how free rotation about
the benziporphyrinꢀCH2 bond does not average out the en-
vironments for the individual protons (labeled HA and HB). The
carbon-13 NMR spectrum of 24 again showed that the macro-
cycle possesses a plane of symmetry and the carbonyl units gave
As porphyrinoid systems like 24 were the main target for this
study, a range of oxidation conditions were considered. Oxidizing
agents such as tert-butyl hydroperoxide, hydrogen peroxide,
bleach, pyridine N-oxide, manganese dioxide, pyridinium chlor-
ochromate, ferric chloride, iron(III) sulfate, iron(III) nitrate, and
air were examined, but most of these trials led to decomposition.
The best results were obtained by dissolving 23 in acetic acid with
5 equiv of ferric chloride and bubbling air through the stirred
solution overnight. Following extraction, chromatography, and
recrystallization from chloroformꢀmethanol, 24 was isolated in
23% yield. However, even taking into account the quantity of 24
generated in the original condensation, the total yield of 24 from
benzitripyrrane 20b was only 11%.
Hydroxyoxybenziporphyrin 23 was also reacted with 1 equiv
of bromine in acetic acid. This led to a straightforward electro-
philic substitution to afford the bromo derivative 26 (Scheme 8).
Following extraction, chromatography, and recrystallization
from chloroformꢀhexanes, 26 was isolated as brown crystals in
44% yield. The UVꢀvis spectrum for the free base form of 26
gave a strong Soret band at 400 nm. On addition of TFA, the
resulting cation 26H+ gave a split Soret band at 411 and 426 nm,
together with a series of Q bands between 500 and 600 nm. The
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Figure 5. 500 MHz proton NMR spectrum of 24 in CDCl3. The
internal CH shows up beyond ꢀ8 ppm, while the meso-protons appear
downfield at 9.5 and 10.3 ppm. The CH2 units of the ethyl substituents
also appear to be diastereotopic. Note that the methyl group on the
tertiary alcohol overlaps with the two triplets for the ethyl substituents.
Figure 7. UVꢀvis spectra of oxabenziporphyrin 28c. Free base in 1%
Et3NꢀCHCl3 (red line). Cation 28cH+ in 1% TFA-CHCl3 (blue line).
Figure 6. Free rotation of the ethyl substituent does not average out the
environment for the two methylene protons HA and HB. The bold line
represents a side view of benziporphyrinoid system 24, and the methyl
and hydroxyl units for the tertiary alcohol moiety differentiate between
the two faces of the macrocycle. Each consecutive Newman projection
represents a 120° rotation about the benziporphyrinꢀCH2 bond. The
same analysis also applies to structures 26, 28, and 30.
rise to a signal at 201.4 ppm. In TFAꢀCDCl3, the proton NMR
spectrum for cation 24H+ showed the internal CH at ꢀ6.4 ppm,
the NH resonances at ꢀ5.67 (1H) and ꢀ2.76 ppm (2H), and the
meso-protons downfield at 10.17 (2H) and 10.88 ppm (2H).
Again, the methyl groups gave a downfield singlet at 3.56 ppm.
Condensation of tripyrrane analogue 20b with thiophene,
selenophene, and furan dialdehydes 14bꢀd, followed by oxida-
tion with 27, all gave heterobenziporphyrinoids 28 (Scheme 6).
Reaction of 14d with 20b initially gave a mixture of 29c and 28c
which was partially purified by chromatography. Oxidation of the
mixture with 0.5 equiv of 27 in the presence of potassium
carbonate was carried out with cooling in an ice bath. The
reaction occurred very rapidly and was complete in approxi-
mately 3 min. Prolonged reaction times led to decomposition.
The reaction solution was immediately washed with water, and
the products were purified by column chromatography. Follow-
ing recrystallization from chloroformꢀhexanes, 28c was isolated
in 20% yield. Using the ferric chloride conditions, this product
could only be isolated in 6% yield. Thiophene dialdehyde 14b
similarly reacted with 20b to give a mixture of 28a and 29a. This
mixture was further oxidized with 0.5 equiv of 27 in the presence
of potassium carbonate for 20 min. Following workup, purifica-
tion by column chromatography, and recrystallization from
chloroformꢀhexanes, the oxidized thiabenziporphyrin 28a was
isolated in 19% yield. This compares to an 8% yield using the
ferric chloride conditions. Selenophene dialdehyde 14c similarly
reacted with tripyrrane analogue 20b to give an analogous
mixture of porphyrinoids 28b and 29b. However, oxidation with
27 was less successful in this case. The oxidized form 28b was
isolated in 8% yield together with crude 29b in 24% yield.
Nevertheless, the ferric chloride oxidation conditions only gave
a trace amount of this oxidation product.
Figure 8. UVꢀvis spectra of thiabenziporphyrin 28a. Free base in 1%
Et3NꢀCHCl3 (red line). Cation 28aH+ in 1% TFAꢀCHCl3 (blue line).
bands between 500 and 670 nm (Figure 7). As was the case of the
related aza-version 24, the cation 28cH+ in TFAꢀCHCl3 gave a
split Soret band at 397 and 432 nm, as well as a series of Q bands
in the visible region (Figure 7). The Soret bands were compara-
tively sharp in this case. The proton NMR spectrum for 28cH+ in
TFAꢀCDCl3 showed the internal CH resonance at ꢀ6.92 ppm,
the NHs at ꢀ3.47 ppm, and the meso-protons at 10.50 and 11.06
ppm. The methyl resonance appeared at 3.65 ppm. These data
show that the monocation is highly diatropic and comparable to
24H+. The carbon-13 NMR spectrum showed 16 resonances,
confirming the plane of symmetry for this macrocycle, and the
carbonyl resonances were observed at 202.1 ppm. Thiabenzi-
porphyrinoid 28a also gave a porphyrin-like UVꢀvis spectrum
with a broad split Soret band at 413 and 436 nm and Q bands at
526, 555, 609, and 665 nm (Figure 8). In TFAꢀCHCl3, a split
Soret band is observed at 423 and 454 nm together with a weaker
band at 601 nm (Figure 8). In the proton NMR spectrum, the
internal CH gave a resonance at ꢀ6.52 ppm, while the meso-
protons appeared at 10.49 and 10.63 ppm (Figure 9). The
The UVꢀvis spectrum for 24-oxaporphyrinoid 28c in
Et3NꢀCHCl3 gave a Soret band at 426 nm and a series of Q
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Figure 9. 500 MHz proton NMR spectrum of thiabenziporphyrin 28a
in CDCl3.
Figure 11. Color ORTEP III drawings (50% probability level, hydro-
gen atoms drawn arbitrarily small) of 28b MeOH. (A) General view.
3
(B) Side view depicting the overall framework planarity with the NH
pyrrole inclined 21° from main macrocyclic plane. Selected bond lengths
(Å): C(1)ꢀC(2) 1.493(2), C(2)ꢀC(3) 1.535(2), C(3)ꢀC(4)
1.523(2), C(4)ꢀC(5) 1.492(2), C(5)ꢀC(22) 1.418(2), C(22)ꢀC(1)
1.409(2), C(5)ꢀC(6) 1.411(2), C(6)ꢀC(7) 1.391(2), C(7)ꢀC(8)
1.437(2), C(8)ꢀC(9) 1.386(2), C(9)ꢀC(10) 1.424(2), C(10)ꢀC-
(11) 1.401(2), C(11)ꢀC(12) 1.387(2), C(12)ꢀC(13) 1.421(2), C-
(13)ꢀC(14) 1.372(2), C(14)ꢀC(15) 1.423(2), C(15)ꢀC(16)
1.380(2), C(16)ꢀC(17) 1.406(2), C(17)ꢀC(18) 1.458(2), C(18)ꢀC-
(19) 1.363(2), C(19)ꢀC(20) 1.478(2), C(20)ꢀC(21) 1.394(2), C-
(21)ꢀC(1) 1.409(2), C(7)ꢀN(23) 1.377(2), N(23)ꢀC(10) 1.384(2),
C(12)ꢀSe(24) 1.895(2), Se(24)ꢀC(15) 1.870(2), C(17)ꢀN(25)
1.358(2), N(25)ꢀC(20) 1.365(2).
Figure 10. UVꢀvis spectra of selenabenziporphyrin 28b. Free base in
1% Et3NꢀCHCl3 (red line). Cation 28bH+ in 1% TFAꢀCHCl3 (blue
line).
macrocycle retains highly diatropic characteristics. The carbon-
13 NMR spectra for 28a and 28b in TFAꢀCDCl3 again confirm
that the macrocycles possess planes of symmetry and show the
carbonyl resonances at 202.1 and 200.9 ppm, respectively.
Spectroscopic data were also obtained for 29b, although it was
contaminated with a small amount of 28b. The UVꢀvis spec-
trum for 29b showed a Soret band at 425 nm and Q bands at 534,
564, 606, and 720 nm. The proton NMR spectrum for 29bH+ in
TFAꢀCDCl3 showed the internal CH at ꢀ0.91 ppm, the methyl
resonance at 3.06 ppm, the selenophene protons at 9.25 ppm,
and the meso-protons at 9.61 and 10.25 ppm.
external thiophene protons were also downfield at 9.99 ppm,
while the methyl protons resonated at 3.48 ppm. Cation 28aH+
in TFAꢀCDCl3 showed the 22-H at ꢀ6.68 ppm, the NH
protons at ꢀ3.77 ppm, the methyl groups at 3.68 ppm, the
thiophene protons at 10.34 ppm, and the meso-protons at 11.11
and 11.22 ppm. Hence, thiabenziporphyrin 28a retains highly
diatropic characteristics for both the free base and cationic forms.
Selenabenziporphyrin 28b gave a porphyrin-like UVꢀvis spec-
trum with a Soret band at 423 nm (Figure 10), although the
bands were broader and less intense than the UVꢀvis spectra of
24 or 28a (oxabenziporphyrin 28c gave much sharper bands than
any of the other porphyrinoids). Similarly, the absorption bands
for 28bH+ in TFAꢀCHCl3 were also relatively broadened
(Figure 10). The proton NMR spectrum for 28b in CDCl3
showed resonance for the 22-H at ꢀ6.36 ppm, the methyl
resonance at 3.42 ppm, the selenophene protons at 10.16 ppm,
and the meso-protons at 10.55 and 10.58 ppm. In TFAꢀCDCl3,
the internal CH appeared at ꢀ5.87 ppm, the NH protons were
observed at ꢀ3.62 ppm, the methyl groups gave a 6H singlet at
3.65 ppm, the selenophene protons were present at 10.26 ppm,
and the meso-protons showed up at 11.17 ppm. Although the
presence of a large selenium atom in the macrocyclic cavity
might be expected to decrease the planarity of this system, the
The X-ray crystal structure of the free base selenabenzipor-
phyrinoid has also been obtained as the methanol solvate 28b
3
MeOH (Figure 11). This not only confirms the presence of a
selenophene moiety but also demonstrates that one pyrrole
moiety must turn out of the main macrocyclic plane to accom-
modate the large Se atom, as evidenced by the 21° incline of the
plane of the NH containing pyrrole relative to the main frame-
work plane defined as the macrocyclic carbon atoms excluding
the NH pyrrole, the two carbonyls, and alcohol C atoms. The β C
atoms of the NH pyrrole are significantly displaced about 0.7 Å
above the framework plane. The sp3 C atom is 0.32 Å above the
plane. In contrast, the selenophene, the pyrrolenine unit, and the
carbocyclic ring excluding the sp3 carbon are fairly coplanar, and
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Scheme 9
Figure 12. Partial 500 MHz proton NMR spectrum of 22-methylben-
ziporphyrin 31a in CDCl3 showing the presence of two different
diastereomers. Each diastereomer gives rise to four different singlets
for the meso-protons between 9.5 and 10.5 ppm. In addition, two singlets
for the internal methyl groups can be seen near ꢀ4.7 ppm, while the 22-H
peaks show up between ꢀ5.8 and ꢀ6.0 ppm.
chromatography on silica afforded a dark orange fraction, and
subsequent recrystallization from chloroformꢀhexanes gave the
expected silver(III) complex 30 in 87% yield. In the proton NMR
spectrum for 30, the meso-protons were observed at 9.19 and 9.91
ppm and the methyl substituents gave rise to a resonance at 3.32
ppm, confirming that the complex retains most of its diatropic
characteristics. The UVꢀvis spectrum for 30 gave a Soret band at
422 nm and three weaker Q bands between 500 and 600 nm. In
1% TFAꢀCHCl3, the silver complex was rapidly demetalated
and the UVꢀvis spectrum showed the formation of cation 24H+.
Bromo derivative 26 was also reacted with silver acetate, but in
this case only very low yields of a silver(III) complex was formed.
Silver(I) cations have a high affinity for halogens and this appears
to lead to side reactions involving loss of bromide ions.
the framework atoms have an rms deviation from their plane
equal to only 0.077 Å. A space-filling diagram reveals that the
large Se atom makes it quite crowded in the center of the ring,
which seems sufficient to justify the NH pyrrole deviating from
planarity. In the solid-state structure, the NH H atom is best
modeled based on residual electron density in the difference
Fourier map and is found to be atypically bent away from the
pyrrole plane. This may in part be due to the solid-state packing
arrangement in which pairs of 28b molecules appear to be
conjoined across a crystallographic inversion center via weak
NH
N hydrogen-bonding interactions. However, the
3 3 3
3.344(2) Å NꢀN separation is rather large, so the apparent
location of this hydrogen atom may simply be due to spatial
overcrowding within the macrocycle. The related system 5,20-
diphenyl-10,15-di-p-tolyl-21-selenaporphyrin, which contains
only one internal H atom, contains a very planar framework,34
while N-confused 5,20-di-p-tolyl-10,15-diphenylthiaporphyrin,
which contains an S atom and two internal H atoms like 28b,
displays a significantly saddled structure.35 However, care must
be taken to avoid exaggerating the correlation between planarity
and apparent internal macrocyclic crowding. A related N-con-
fused pyriporphyrin, 6,21-diphenyl-11,16-di-p-tolyl-3-aza-24-
thiabenziporphyrin, has a saddled framework conformation, yet
only possesses a single internal H atom.36 In fact, analysis of the
2010 Cambridge Structural Database showed that the 15 pre-
viously reported X-ray structural characterizations of monothia-
porphyrins and monoselenaporphyrins37 lack clear trends in
solid state macrocyclic planarity. The structure also shows the
six-membered ring methyl unit in a pseudoaxial orientation,
while the hydroxyl group is pseudoequatorial. This may be due
to favored hydrogen bonding with the methanol solvate within
the crystal lattice.
Many carbaporphyrinoid systems, including N-confused
porphyrins,38 oxybenziporphyrins,13,39 oxynaphthiporphyrins,13,39
benzocarbaporphyrins,40 and tropiporphyrins,41 act as trianionic
ligands and readily form silver(III) organometallic derivatives.39
These porphyrin analogues all possess a CH NH N NH
arrangement of core atoms.42ꢀ44 As the core atoms in oxidized
benziporphyrin 24 are arranged in the same way, we anticipated
that a similar organometallic derivative could be prepared for this
species. Silver(I) acetate was stirred with 24 in a mixture of
methanol and dichloromethane for 16 h (Scheme 9). Flash
Porphyrinoid 24 was also reacted with alkyl iodides to
investigate the possibility of introducing N-alkyl substituents.
Reaction of 24 with methyl iodide and potassium carbonate was
carried out in refluxing acetone (Scheme 7). Following chroma-
tography on silica, the product was collected as a dark purple
fraction in 70% yield. The proton NMR spectrum showed that
the product consisted on a mixture of two alkylation products in a
ratio of approximately 2:1. Both products had four different
resonances for the meso-protons and no longer showed the
presence of a plane of symmetry (Figure 12). On the basis of
these observations, the methyl substituent must have been
introduced onto a pyrrolic unit next to the carbocyclic ring. As
the methyl group is too large to pass through the central cavity,
two diastereomers are possible where the alkyl substituent is
either cis or trans to the peripheral OH group. The spectroscopic
data did not allow us to identify which stereoisomer was favored.
The methyl group does not undermine the diatropicity of this
system. In the proton NMR spectrum for the mixture, the major
diastereomer showed the internal CH at ꢀ5.73 ppm and the
N-methyl at ꢀ4.54 ppm, while the meso-protons gave singlets at
9.62, 9.71, 10.52, and 10.54 ppm (Figure 12). The minor
diastereomer gave the 22-H singlet at ꢀ5.84 ppm and the
N-methyl resonance at ꢀ4.71 ppm, and the meso-protons appeared
at 9.69, 9.74, 10.18, and 10.47 ppm (Figure 12). Reaction of 24
with ethyl iodide gave similar results, although in this case it was
necessary to raise the temperature by using refluxing methyl ethyl
ketone as the solvent. A mixture of two diastereomers, again in a
ratio of approximately 2:1, was obtained in 67% yield, and the
same regioselectivity was observed. The environment for the
N-ethyl groups shows a high degree of chiral discrimination. In
the proton NMR spectrum, the major diastereomer showed the
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removed under reduced pressure, and the resulting red residue was
chromatographed on silica gel eluting with 15% ethyl acetateꢀtoluene.
The product was collected as an orange fraction. Recrystallization from
chloroformꢀhexanes afforded the tripyrrane analogue (0.373 g, 0.602
mmol, 33%) as white crystals: mp 216ꢀ217 °C; 1H NMR (500 MHz,
DMSO-d6) δ 0.70 (6H, t, J = 7.5 Hz), 2.10 (4H, q, J = 7.5 Hz), 2.11 (6H,
s), 3.57 (4H, s), 5.20 (4H, s), 6.16 (1H, s), 6.34 (1H, s), 7.30 (2H, t, J =
7.1 Hz), 7.36 (4H, t, J = 7.4 Hz), 7.40 (4H, d, J = 7.3 Hz), 9.16 (2H, s),
10.69 (2H, s); 13C NMR (DMSO-d6) δ 10.4, 15.2, 16.7, 24.9, 64.3,
102.2, 115.6, 116.4, 123.1, 126.2, 127.7, 127.8, 128.5, 129.8, 133.6, 137.2,
153.3, 160.6; HRMS (FAB) calcd for C38H40N2O6 + H m/z 621.2965,
found 621.2964. Anal. Calcd for C38H40N2O6: C, 73.53; H, 6.49; N,
4.51. Found: C, 73.66; H, 6.44; N, 4.53.
4,6-Bis(5-carboxy-3-ethyl-4-methyl-2-pyrrolylmethyl)-1,3-
dihydroxybenzene (20a). In a hydrogenation vessel, the foregoing
tripyrrane analogue (897 mg, 1.45 mmol) was dissolved in freshly
distilled THF (150 mL) and methanol (50 mL), and the solution was
purged with nitrogen. Then, 10% palladiumꢀcharcoal (200 mg) was
added, and the resulting mixture was shaken under an atmosphere of
hydrogen at 40 psi at room temperature overnight. The catalyst was
filtered off and the solvent removed in vacuo to yield the dicarboxylic
acid (0.632 g, 1.44 mmol, 99%) as pink crystals: mp 134ꢀ135 °C; 1H
NMR (400 MHz, DMSO-d6) δ 0.75 (6H, t, J = 7.4 Hz), 2.11 (6H, s),
2.17 (4H, q, J = 7.4 Hz), 3.56 (4H, s), 6.37 (1H, s), 6.39 (1H, s), 9.24
(2H, s), 10.38 (2H, s), 11.72 (2H, br s); 13C NMR (DMSO-d6) δ 10.2,
15.4, 16.8, 25.2, 102.4, 116.6, 122.5, 125.1, 130.5, 132.6, 153.4, 162.4.
Anal. Calcd for C24H28N2O6: C, 65.44; H, 6.41; N, 6.36. Found: C,
65.55; H, 6.52; N, 6.15.
4,6-Bis(5-benzyloxycarbonyl-3-ethyl-4-methyl-2-pyrroly-
lmethyl)-1,3-dihydroxy-2-methylbenzene (17b). A solution of
acetoxymethylpyrrole 1847 (3.60 g, 11.4 mmol) in dichloromethane
(80 mL) was slowly added over a 10 h period using a syringe pump to a
stirred mixture of 2-methylresorcinol (0.720 g, 5.8 mmol), p-toluene-
sulfonic acid monohydrate (0.60 g), and calcium chloride (8.15 g) in
dichloromethane (120 mL). The resulting mixture was stirred for a
further 6 h and then washed with water and saturated sodium bicarbo-
nate solution. The solvent was removed under reduced pressure and the
resulting oily residue chromatographed on silica gel eluting with 10%
ethyl acetateꢀtoluene. The product was collected as an orange fraction.
Recrystallization from chloroformꢀhexanes afforded the tripyrrane
analogue (1.107 g, 1.75 mmol, 30%) as pink crystals: mp 161ꢀ163 °C;
1H NMR (400 MHz, CDCl3) δ 1.03 (6H, t, J = 7.4 Hz), 1.90 (3H, s),
2.27 (6H, s), 2.44 (4H, q, J = 7.6 Hz), 3.76 (4H, s), 5.24 (4H, s), 5.37
(2H, br s), 6.66 (1H, s), 7.27ꢀ7.38 (10H, m), 8.95 (2H, br s); 13C NMR
(CDCl3) δ 8.6, 10.8, 15.7, 17.4, 27.3, 65.7, 111.4, 117.55, 117.60, 124.2,
127.4, 128.1, 128.7, 128.9, 132.2, 136.9, 151.6, 161.9; HRMS (FAB)
calcd for C39H42N2O6 + H m/z 635.3121, found 635.3124. Anal. Calcd
for C39H42N2O6: C, 73.79; H, 6.67; N, 4.41. Found: C, 73.43; H, 6.65;
N, 4.47.
4,6-Bis(5-carboxy-3-ethyl-4-methyl-2-pyrrolylmethyl)-1,3-
dihydroxy-2-methylbenzene (20b). Dibenzyl ester 17b (1.022 g,
1.61 mmol) was dissolved in freshly distilled THF (150 mL) and
methanol (50 mL) and the solution purged with nitrogen. Then, 10%
palladiumꢀcharcoal (200 mg) was added and the resulting mixture
shaken under an atmosphere of hydrogen at 40 psi at room tempera-
ture overnight. The catalyst was filtered off, and the solvent was
removed in vacuo to yield the dicarboxylic acid (0.709 g, 1.56 mmol,
97%) as red crystals: mp 141ꢀ142 °C; 1H NMR (500 MHz, DMSO-
d6) δ 0.75 (6H, t, J = 7.5 Hz), 2.04 (3H, s), 2.12 (6H, s), 2.13 (4H, q, J =
7.5 Hz), 3.62 (4H, s), 6.19 (1H, s), 8.09 (2H, s), 10.44 (2H, s), 11.66
(2H, v br); 13C NMR (DMSO-d6) δ 10.1, 10.3, 15.3, 16.8, 25.8, 112.5,
116.6, 118.3, 122.7, 125.3, 126.7, 132.2, 151.1, 162.5. Anal. Calcd for
C25H30N2O6: C, 66.06; H, 6.65; N, 6.16. Found: C, 66.44; H, 7.14;
N, 5.81.
Figure 13. Partial 500 MHz proton NMR spectrum of 22-ethylbenzi-
porphyrin 31b in CDCl3 showing details of the upfield region. Two
diastereomers are present that give two sets of peaks for the internal
ethyl substituents and the 22-Hs. The methylene protons are highly
diastereotopic, demonstrating that they lie in a stereochemically dis-
criminating region for these chiral derivatives.
internal methylene protons as two 1H multiplets at ꢀ5.3 and ꢀ4.9
ppm, showing that the two diastereotopic protons reside in
significantly different environments (Figure 13). The strongly
diatropic nature of the macrocycle was confirmed by the presence
of the 22-H resonance at ꢀ5.76 ppm and the presence of four
downfield singlets for the meso-protons at 9.70, 9.71, 10.53, and
10.61 ppm. Similar results were noted for the minor diastereomer,
which again showed strongly differentiated methylene proton
resonances for the internal ethyl group at ꢀ5.41 and ꢀ5.11 ppm.
Both diastereomers consist of a pair of enantiomers, and this system
therefore shows potential in the design of chiral catalysts.45
’ CONCLUSION
Tripyrrane analogues have been prepared from resorcinol and
2-methylresorcinol and used as intermediates in the synthesis of
hydroxyoxybenziporphyrins and further oxidized derivatives.
The initial products derived from the reaction of the methylre-
sorcinol-derived tripyrrane analogue with pyrrole, furan, thio-
phene, or selenophene dialdehydes were unstable, but further
oxidation with [bis(trifluoroacetoxy)iodo]benzene gave highly
diatropic benziporphyrins with porphyrin-like UVꢀvis spectra.
These results show that modified benziporphyrins can be highly
aromatic systems even though simple benziporphyrins are usua-
lly considered to be devoid of macrocyclic aromatic properties.
An oxidized benziporphyrin was shown to readily form a silver-
(III) derivative and also underwent a regioselective alkylation to
give mixtures of chiral diastereomers. The unusual characteristics
of these carbaporphyrinoids suggest that the full potential of
benziporphyrin systems remains to be discovered.46
’ EXPERIMENTAL SECTION
4,6-Bis(5-benzyloxycarbonyl-3-ethyl-4-methyl-2-pyrrolyl-
methyl)-1,3-dihydroxybenzene (17a). A solution of benzyl
5-acetoxymethyl-4-ethyl-3-methylpyrrole-2-carboxylate47 (1.20 g, 3.81
mmol) in dichloromethane (70 mL) was added to a stirred mixture of
resorcinol (0.20 g, 1.8 mmol), p-toluenesulfonic acid monohydrate
(0.20 g), and calcium chloride (2.72 g) in dichloromethane (40 mL)
in a 200 mL round-bottom flask over a 10 h period using a syringe pump.
The resulting mixture was stirred for a further 6 h and then washed with
water and saturated sodium bicarbonate solution. The solvent was
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8,13,14,19-Tetraethyl-4-hydroxy-9,18-dimethyl-2-oxy-
benziporphyrin (21). In a 100 mL pear-shaped flask, tripyrrane
analogue 20a (75.0 mg, 0.17 mmol) and TFA (1 mL) were stirred under
nitrogen for 2 min. Dichloromethane (99 mL) was added, followed
immediately by pyrrole dialdehyde 14a31 (30.5 mg, 0.17 mmol), and the
resulting mixture was stirred overnight under nitrogen. The mixture was
shaken vigorously with aqueous 0.1% w/v ferric chloride solution
(100 mL) for 5 min, and the aqueous solution was then back-extracted
with chloroform. The combined organic solutions were washed with
water and 5% aqueous sodium bicarbonate solution, the solvent was
removed under reduced pressure, and the resulting dark blue residue was
chromatographed on flash silica eluting with 5% methanolꢀchloroform.
The product was collected as a dark brown fraction. Recrystallization
from chloroformꢀhexanes yielded the oxybenziporphyrin (31.3 mg,
0.063 mmol, 37%) as brown crystals: mp >300 °C; UVꢀvis (2% Et3Nꢀ
CHCl3) λmax (log10ε) 422 (5.08), 455 (sh, 4.30), 528 (3.91), 570 (4.14),
620 (3.72), 684 nm (3.44); UVꢀvis (2% DBUꢀCHCl3) λmax (log10ε)
409 (5.02), 519 (3.98), 559 (4.06), 616 (3.70), 678 nm (3.25); UVꢀvis
(3 equiv TFAꢀCHCl3) λmax (log10ε) 410 (5.10), 427 (5.15), 471
(3.96), 535 (3.85), 569 (sh, 3.84), 584 (4.09), 730 nm (3.31); UVꢀvis
(200 equiv TFAꢀCHCl3) λmax (log10ε) 316 (4.32), 368 (4.53), 429
(5.02), 470 (4.23), 555 (3.70), 601 (4.22), 653 (sh, 3.70), 717 nm
(3.74); IR (KBr) 3440 (OH str.), 1611 (CdO str); 1H NMR (500 MHz,
TFAꢀCDCl3) δ ꢀ2.35 (1H, s), ꢀ0.81 (1H, br s), 1.51 (6H, t, J = 7.7
Hz), 1.68 (6H, t, J = 7.7 Hz), 2.42 (2H, br s), 3.12 (6H, s), 3.62ꢀ3.71
(8H, m), 7.59 (1H, s), 8.89 (2H, s), 10.10 (2H, s); 13C NMR (TFAꢀ
CDCl3) δ 11.0, 16.4, 17.0, 19.4, 19.9, 94.1, 105.8, 117.0, 117.2, 117.3,
133.8, 138.4, 144.7, 144.8, 150.5, 151.3, 176.7; HRMS (EI) calcd for
C32H35N3O2 + H 494.2808, found 494.2808. Anal. Calcd for
0.53 mmol) was added, and air was bubbled through the stirred mixture
overnight. Chloroform was added and the mixture washed with water
followed by saturated sodium bicarbonate. The solvent was evaporated
under reduced pressure and the residue chromatographed on flash silica,
eluting with 50% dichloromethaneꢀchloroform. The product was
collected as a red fraction. Recrystallization from chloroformꢀmethanol
yielded the porphyrin analogue (13.1 mg, 0.025 mmol, 23%; 11% total
yield from 20b) as red crystals: mp >300 °C; UVꢀvis (1% Et3Nꢀ
CHCl3) λmax (log10ε) 384 (sh, 4.90) 417 (5.11), 509 (4.14), 544 (4.08),
593 nm (3.75); UVꢀvis (1% TFAꢀCHCl3) λmax (log10ε) 411 (5.32),
426 (5.32), 533 (4.08), 569 (3.93), 584 nm (4.08); IR (KBr) 1699,
1661 cmꢀ1 (CdO str); 1H NMR (500 MHz, CDCl3) δ ꢀ8.04 (1H, s),
1.76ꢀ1.81 (15H, overlapping singlet and triplets), 3.53 (6H, s),
3.81ꢀ3.88 (4H, m), 4.01ꢀ4.13 (4H, m), 9.50 (2H, s), 10.31 (2H, s);
1H NMR (500 MHz, TFAꢀCDCl3) δ ꢀ6.38 (1H, s), ꢀ5.67 (1H, s),
ꢀ2.76 (2H, s), 1.51 (3H, s), 1.62 (6H, t, J = 7.7 Hz), 1.87 (6H, t, J = 7.7
Hz), 3.56 (6H, s), 4.00ꢀ4.16 (8H, m), 10.17 (2H, s), 10.88 (2H, s); 13
C
NMR (CDCl3) δ 11.2, 17.5, 18.5, 19.9, 20.0, 30.2, 86.2, 94.9, 103.2,
119.7, 120.1, 130.4, 131.3, 138.4, 143.5, 145.1, 154.3, 201.4; 13C NMR
(TFAꢀCDCl3) δ 11.7, 16.7, 17.5, 20.0, 20.3, 28.7, 87.3, 94.2, 110.5,
121.0, 129.1, 134.6, 137.1, 139.0, 142.2, 143.6, 147.0, 203.4; HRMS
(FAB) calcd for C33H37N3O3 + H 524.2913, found 524.2916. Anal.
Calcd for C33H37N3O3: C, 75.69; H, 7.12; N, 8.02. Found: C, 75.42; H,
6.94; N, 8.05.
Method B. TFA (1 mL) was added to tripyrrane dicarboxylic acid 20b
(90.8 mg, 0.200 mmol) in a 100 mL pear-shaped flask and the mixture
stirred under nitrogen for 2 min. Dichloromethane (99 mL) was added,
following immediately by pyrrole dialdehyde 14a31 (35.8 mg, 0.200
mmol), and the resulting mixture stirred overnight under nitrogen. The
mixture was shaken vigorously with aqueous 0.1% ferric chloride
solution (100 mL) for 5 min and then washed with water and saturated
sodium bicarbonate, back-extracting at each stage with chloroform. The
solvent was removed under reduced pressure and the resulting brown
residue chromatographed on a flash silica column with 1.7% metha-
nolꢀchloroform. Porphyrinoids 23 and 24 were collected as brown and
red fractions, respectively. Evaporation of the two fractions separately
gave brown and red residues. Porphyrin analogue 23 was collected as the
major fraction, and 24 was isolated as a minor product. Crude
porphyrinoid 23 was dissolved in 15 mL of 50% methanolꢀ
dichloromethane. [Bis(trifluoroacetoxy)iodo]benzene (27) (35.5 mg,
0.08 mmol) and potassium carbonate (250 mg) were added to the
stirred mixture, and the reaction was monitored by UVꢀvis spectros-
copy (the reaction may take 30 min). The resulting solution was washed
with water, back-extracting with chloroform, and following evaporation
of the solvent, the crude product was obtained as a dark green solid.
Flash chromatography, eluting with 50% dichloromethaneꢀchloroform,
gave 24 as a red fraction. Recrystallization from chloroformꢀmethanol
gave 24 (25.2 mg, 0.048 mmol, 24% overall yield from 20b) as a red
powder, mp >300 °C.
8,13,14,19-Tetraethyl-3,4-dihydro-3-hydroxy-3,9,18-tri-
methyl-4-oxo-24-oxa-2-oxybenziporphyrin (28c). TFA (1 mL)
was added to tripyrranedicarboxylic acid 20b (75.0 mg, 0.165 mmol) in a
100 mL pear-shaped flask and the mixture stirred under nitrogen for
2 min. Dichloromethane (100 mL) was added, followed immediately by
furan dialdehyde 14d (20.4 mg, 0.165 mmol), and the resulting mixture
stirred overnight under nitrogen. The mixture was washed with aqueous
0.1% ferric chloride solution (100 mL), water, and saturated sodium
bicarbonate, back-extracting at each stage with chloroform. The solvent
was removed under reduced pressure and the resulting brown residue
chromatographed on a flash silica column with 3% methanolꢀchloro-
form. Porphyrinoids 29c and 28c were collected as overlapping brown
and red fractions. Evaporation of the combined fractions gave a brown re-
sidue, and this was dissolved in 10 mL of 50% methanolꢀdichloromethane
and cooled in an ice bath. [Bis(trifluoroacetoxy)iodo]benzene (27)
C32H35N3O2 1/4CHCl3: C, 73.99; H, 6.79; N, 8.02. Found: C, 73.96;
3
H, 6.84; N, 7.88.
8,13,14,19-Tetraethyl-4-hydroxy-3,9,18-trimethyl-2-oxy-
benziporphyrin (23). Tripyrrane analogue 20b (225.1 mg, 0.496
mmol) was stirred with TFA (3 mL) under nitrogen for 2 min.
Dichloromethane (300 mL) was added, followed immediately by
dialdehyde 14a31 (89.0 mg, 0.497 mmol), and the resulting mixture
was stirred overnight under nitrogen. The mixture was washed with
aqueous 0.1% ferric chloride solution (300 mL), water, and 5% sodium
bicarbonate, back-extracting at each at stage with chloroform. The
solvent was removed under reduced pressure and the resulting dark
brown residue chromatographed on flash silica eluting with 1.7%
methanolꢀchloroform. The crude product was collected as a dark
brown fraction. The solvent was removed under reduced pressure and
the resulting brown residue chromatographed on flash silica eluting with
50% dichloromethaneꢀchloroform. Initially, 24 was collected as a red
fraction. Recrystallization from chloroformꢀmethanol yielded oxyben-
ziporphyrin 24 (13.2 mg, 0.0252 mmol, 5%) as red crystals, mp >300 °C.
A later brown fraction was collected and recrystallized from chloroform-
hexanes to yield the porphyrin analogue 23 (68.2 mg, 0.134 mmol, 27%)
as brown crystals: mp >300 °C; UVꢀvis (Et3NꢀCHCl3) λmax (log10ε)
423 (5.05), 457 (sh, 4.29), 509 (3.84), 542 (3.90), 576 (4.06), 626
(3.57), 691 nm (3.29); UVꢀvis (1% TFAꢀCHCl3) λmax (log10ε) 412
(4.98), 427 (5.09), 555 (3.81), 603 (4.02), 627 (sh, 3.77), 688 nm
(3.45); 1H NMR (500 MHz, TFAꢀCDCl3) δ ꢀ1.14 (1H, s), 1.44 (6H,
t, J = 7.7 Hz), 1.60 (6H, t, J = 7.7 Hz), 2.48 (3H, s), 2.98 (6H, s), 3.18
(2H, br s), 3.49ꢀ3.56 (8H, m), 8.54 (2H, s), 9.72 (2H, s); 13C NMR
(TFAꢀCDCl3) δ 8.4, 10.7, 15.9, 16.3, 19.2, 19.8, 93.9, 110.8, 114.0,
116.5, 118.7, 134.3, 139.2, 145.7, 147.2, 153.0, 153.4, 170.7; HRMS (EI)
calcd for C33H37N3O2 507.2886, found 507.2876.
8,13,14,19-Tetraethyl-3,4-dihydro-3-hydroxy-3,9,18-tri-
methyl-4-oxo-2-oxybenziporphyrin (24). Method A. The par-
tially purified hydroxyoxybenziporphyrin 23 (54.1 mg, 0.107 mmol) was
dissolved in acetic acid (60 mL) and placed in a 100 mL three-neck
round-bottom flask. Five equivalents of ferric chloride (87.0 mg,
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ARTICLE
(35.5 mg, 0.082 mmol) and potassium carbonate (250 mg) were added to
the stirred mixture, and the reaction was monitored by UVꢀvis spectros-
copy so that the reaction could be stopped as soon as the conversion was
complete. This usually took no more than 3 min. The resulting solution
was washed with water, back-extracting with chloroform, and following
evaporation of the solvent the crude product was obtained as a brown
solid. Flash chromatography, eluting with 2.5% methanolꢀchloroform,
gave28c asa red fraction. Recrystallization fromchloroformꢀhexane gave
the product (15.1 mg, 0.032 mmol, 20%) as a brown powder: mp
>300 °C; UVꢀvis (1% Et3NꢀCHCl3) λmax (log10ε) 397 (4.75), 426
(4.80), 516 (3.95), 546 (3.88), 600 (3.82), 656 nm (3.59); UVꢀvis (1%
TFAꢀCHCl3) λmax (log10ε) 397 (5.14), 432 (5.21), 550 (3.95), 576 nm
(4.07); 1H NMR(500 MHz, TFAꢀCDCl3) δ ꢀ6.92 (1H, s), ꢀ3.47(2H,
br s), 1.50 (3H, s), 1.72 (6H, t, J = 7.7 Hz), 3.65 (6H, s), 4.10ꢀ4.24 (4H,
m), 10.14 (2H, s), 10.50 (2H, s), 11.06 (2H, s); 13C NMR (TFAꢀ
CDCl3) δ 11.6, 17.2, 20.3, 28.4, 87.5, 95.6, 112.0, 122.7, 130.1, 131.1,
135.0, 136.8, 139.8, 147.4, 154.2, 202.1; HR MS (ESI) calcd for
C29H28N2O4 + H 469.2127, found 469.2134. Anal. Calcd for
extracting at each stage with chloroform. The solvent was removed
under reduced pressure and the resulting green residue chromato-
graphed on a flash silica column eluting initially with chloroform, and
then the polarity was gradually increased to 3% methanolꢀchloroform.
Porphyrinoids 28b and 29b were collected as green and brown fractions.
Evaporation of the two fractions separately gave dark green residues.
Selenabenziporphyrin 29b was collected as the major fraction (29.3 mg,
0.057 mmol, 35%), and 28b was isolated as a minor product (1.0 mg,
0.0019 mmol, 1.2%).
Porphyrinoid 29b (29.3 mg, 0.0568) was dissolved in 20 mL of 50%
methanolꢀdichloromethane and cooled in an ice bath. [Bis(trifluoroacetoxy)-
iodo]benzene (27) (35.5 mg, 0.082 mmol) and potassium carbonate
(250 mg) were added to the stirred mixture, and the reaction was
monitored by UVꢀvis spectroscopy (the reaction may take 30 min).
The resulting solution was washed with water, back-extracting with
chloroform, and following evaporation of the solvent, the crude product
was obtained as a dark green solid. Flash chromatography, eluting with
chloroform, gave 28b as a green fraction. However, only partial conver-
sion occurred, and 29b was also obtained as a later fraction. Recrystalli-
zation of the individual products from chloroformꢀhexane gave 28b
(7.1 mg, 0.013 mmol, 9.4% overall) as a brown powder and 29b (20.6
mg, 0.040 mmol, 25%) as a green powder.
8,19-Diethyl-4-hydroxy-3,9,18-trimethyl-24-selena-2-oxy-
benziporphyrin (29b): mp >300 °C; UVꢀvis (1% Et3NꢀCHCl3)
λmax (log10ε) 425 (4.86), 534 (3.99), 564 (3.97), 606 (3.96), 720 nm
(3.61); UVꢀvis (1% TFAꢀCHCl3) λmax (log10ε) 394 (4.53), 478
(4.87), 519 (4.83), 627 nm (3.68); 1H NMR (500 MHz, TFAꢀCDCl3)
δ ꢀ0.91 (1H, s), 1.57 (6H, t, J = 7.7 Hz), 2.56 (3H, s), 3.06 (6H, s), 3.64
(4H, q, J = 7.7 Hz), 9.25 (2H, s), 9.61 (2H, s), 10.25 (2H, s); 13C NMR
(TFAꢀCDCl3) δ 9.1, 10.7, 16.3, 19.9, 114.0, 114.7, 118.3, 123.2, 134.9,
137.2, 142.9, 154.7, 155.8, 159.2, 173.7. HR MS (ESI) calcd for
C29H28N2O2Se + H 517.1394, found 517.1373.
C29H28N2O4 0.3CHCl3: C, 69.78; H, 5.65; N, 5.55. Found: C, 70.02;
3
H, 5.72; N, 5.14.
8,19-Diethyl-3,4-dihydro-3-hydroxy-3,9,18-trimethyl-4-oxo-
24-thia-2-oxybenziporphyrin (28a). TFA (1 mL) was added to
dicarboxylic acid 20b (75.0 mg, 0.165 mmol) in a 100 mL pear-shaped
flask and the mixture stirred under nitrogen for 2 min. Dichloromethane
(100 mL) was added, followed immediately by thiophene dialdehyde
14b (23.1 mg, 0.165 mmol), and the resulting mixture stirred overnight
under nitrogen. The mixture was washed with aqueous 0.1% ferric
chloride solution (100 mL), water, and saturated sodium bicarbonate,
back-extracting at each stage with chloroform. The solvent was removed
under reduced pressure and the resulting green residue chromato-
graphed on a flash silica column with 3% methanolꢀchloroform.
Porphyrinoids 29a and 28a were collected as green fractions. Evapora-
tion of the combined fractions gave a dark green residue, and this was
dissolved in 15 mL of 50% methanolꢀdichloromethane and cooled in an
ice bath. [Bis(trifluoroacetoxy)iodo]benzene (27) (35.5 mg, 0.082
mmol) and potassium carbonate (250 mg) were added to the stirred
mixture, and the reaction was stopped after 20 min. The resulting
solution was washed with water, back-extracting with chloroform, and
following evaporation of the solvent, the crude product was obtained as a
dark green solid. Flash chromatography, eluting with chloroform, gave
28a as a green fraction. Recrystallization from chloroformꢀhexane gave
the product (15.3 mg, 0.0316 mmol, 19%) as a green powder: mp
>300 °C; UVꢀvis (1% Et3NꢀCHCl3) λmax (log10ε) 413 (4.86), 436
(4.81), 526 (3.96), 555 (3.73), 609 (3.71), 665 nm (3.16); UVꢀvis (1%
TFAꢀCHCl3) λmax (log10ε) 348 (4.10), 423 (5.04), 454 (5.00), 601 nm
(4.00); 1H NMR (500 MHz, CDCl3) δ ꢀ6.52 (1H, s), ꢀ5.07 (1H, v br),
1.79 (6H, t, J = 7.7 Hz), 1.81 (3H, s), 3.48 (6H, s), 3.95ꢀ4.03 (4H, m),
5.00 (1H, s), 9.99 (2H, s), 10.49 (2H, s), 10.63 (2H, s); 1H NMR (500
MHz, TFAꢀCDCl3) δ ꢀ6.68 (1H, s), ꢀ3.77 (2H, br s), 1.58 (3H, s),
1.77 (6H, t, J = 7.7 Hz), 3.68 (6H, s), 4.11ꢀ4.24 (4H, m), 10.34 (2H, s),
11.11 (2H, s), 11.22 (2H, s); 13C NMR (TFAꢀCDCl3) δ 11.9, 17.1,
20.2, 28.4, 88.0, 109.4, 112.4, 125.2, 128.9, 136.4, 136.9, 138.5, 143.7,
146.6, 202.1; HRMS (ESI) calcd for C29H28N2O3S + H 485.1899, found
8,19-Diethyl-3,4-dihydro-3-hydroxy-3,9,18-trimethyl-4-
oxo-24-seleno-2-oxybenziporphyrin (28b): mp >300 °C;
UVꢀvis (1% Et3NꢀCHCl3) λmax (log10ε) 423 (4.91), 438 (sh, 4.86),
533 (3.89), 577 (3.87), 613 (3.81); UVꢀvis (1% TFAꢀCHCl3) λmax
(log10ε) 395 (4.48), 459 (4.81), 480 (4.88), 622 nm (4.00); 1H NMR
(500 MHz, CDCl3) δ ꢀ6.36 (1H, s), ꢀ5.1 (1H, v br), 1.76 (6H, t, J = 7.6
Hz), 1.80 (3H, s), 3.42 (6H, s), 3.88ꢀ3.97 (4H, m), 5.03 (1H, s), 10.16
(2H, s), 10.55 (2H, s), 10.58 (2H, s); 1H NMR (500 MHz,
TFAꢀCDCl3) δ ꢀ5.87 (1H, s), ꢀ3.62 (2H, br s), 1.58 (3H, s), 1.79
(6H, t, J = 7.7 Hz), 3.65 (6H, s), 4.10ꢀ4.23 (4H, m), 10.26 (2H, s),
11.17 (4H, s); 13C NMR (TFAꢀCDCl3) δ 11.8, 17.1, 20.2, 28.4, 87.9,
113.1, 113.2, 124.2, 126.4, 136.4, 137.3, 139.1, 146.1, 148.1, 155.3, 202.0;
HRMS (ESI) calcd for C29H28N2O3Se + H 533.1343, found 533.1342.
3-Bromo-8,13,14,19-tetraethyl-3,4-dihydro-3-hydroxy-
3,9,18-trimethyl-4-oxo-2-oxybenziporphyrin (26). Bromine in
acetic acid (36%; 106 μL; 1 equiv) was added to a stirred solution of 23
(10.0 mg, 0.019 mmol) in acetic acid (10 mL). The reaction mixture was
stirred for 5 min and diluted with chloroform. The solution was washed
with water, followed by saturated sodium bicarbonate solution, back-
extracting with chloroform. The combined organic layers were evapo-
rated down to dryness under reduced pressure, and the resulting brown
residue was chromatographed on flash silica eluting with 50% dichlor-
omethaneꢀchloroform. The product fraction was collected and recrys-
tallized from chloroformꢀhexanes to yield the bromo compound (5.1
mg, 0.0087 mmol, 45%) as brown crystals: mp >300 °C; UVꢀvis (1%
Et3NꢀCHCl3) λmax (log10ε) 400 (5.10), 513 (4.00), 546 (4.00), 596
(3.62), 657 nm (2.89); UVꢀvis (1% TFAꢀCHCl3): λmax (log10ε) 411
1
485.1920. Anal. Calcd for C29H28N2O3S /10CHCl3: C, 70.39; H, 5.70;
3
N, 5.64. Found: C, 70.32; H, 5.48; N, 5.64.
Reaction of Tripyrrane Analogue 20b with 2,5-Seleno-
phenedicarbaldehyde 14c. TFA (1 mL) was added to benzitri-
pyrrane dicarboxylic acid 20b (75.0 mg, 0.165 mmol) in a 100 mL
pear-shaped flask and the mixture stirred under nitrogen for 2 min.
Dichloromethane (100 mL) was added, following immediately by seleno-
phenedialdehyde 14c (30.1 mg, 0.165 mmol), and the resulting mixture
stirred overnight under nitrogen. The mixture was shaken vigorously
with aqueous 0.1% ferric chloride solution (100 mL) for 5 min and then
washed with water and saturated sodium bicarbonate solution, back-
1
(5.13), 426 (5.14), 534 (3.95), 570 (3.87), 586 nm (3.97); H NMR
(500 MHz, CDCl3) δ ꢀ7.45 (1H, s), 1.83 (12H, t, J = 7.7 Hz), 2.78 (3H,
s), 3.59 (6H, s), 3.91 (4H, q, J = 7.7 Hz), 4.09ꢀ4.17 (4H, m), 9.72 (2H,
s), 10.58 (2H, s); 1H NMR (500 MHz, TFAꢀCDCl3) δ ꢀ6.55 (1H, s),
ꢀ5.63 (1H, br s), ꢀ2.68 (2H, br s), 1.61 (6H, t, J = 7.7 Hz), 1.88 (6H, t,
6305
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The Journal of Organic Chemistry
ARTICLE
J = 7.7 Hz), 2.75 (3H, s), 3.55 (6H, s), 4.05ꢀ4.15 (8H, m), 10.13 (2H,
s), 10.90 (2H, s); 13C NMR (CDCl3) δ 11.3, 17.5, 18.5, 19.9, 20.1, 21.0,
59.9, 95.0, 104.5, 119.0, 120.0, 130.4, 131.6, 138.9, 143.8, 145.2, 154.7,
194.5; FD MS m/z (rel int) 585 (M+, 100), 586 (44), 587 (99), 589
(41). Anal. Calcd for C33H36BrN3O2: C, 67.57; H, 6.19; N, 7.16. Found:
C, 67.42; H, 6.17; N, 7.11.
diastereomers in a ratio of approximately 2:1: UVꢀvis (1% Et3Nꢀ
CHCl3) λmax (rel int) 413 (1.00), 528 (0.11), 564 (0.09), 592 (0.09),
647 nm (0.05); UVꢀvis (1% TFAꢀCHCl3) λmax (rel int) 406 (1.00),
419 (0.91), 525 (0.08), 580 nm (0.08); 1H NMR (major diastereomer,
CDCl3) δ ꢀ5.76 (1H, s), ꢀ5.31 (1H, m), ꢀ4.90 (1H, m), ꢀ3.18 (1H,
br s), ꢀ2.07 (3H, t, J = 7.0 Hz), 1.29 (3H, t,, J = 7.6 Hz), 1.63 (3H, s),
1.78 (3H, t, J = 7.7 Hz), 1.86ꢀ1.92 (6H, m), 3.19 (3H, s), 3.45 (3H, s),
3.69ꢀ3.84 (2H, m), 3.89ꢀ4.09 (6H, m), 9.70 (1H, s), 9.71 (1H, s),
10.53 (1H, s), 10.61 (1H, s); 1H NMR (minor diastereomer, CDCl3) δ
ꢀ5.92 (1H, s), ꢀ5.41 (1H, m), ꢀ5.11 (1H, m), ꢀ3.18 (1H, br s), ꢀ2.20
(3H, t, J = 7.8 Hz), 1.35 (3H, t, J = 7.7 Hz), 1.78 (3H, s), 1.81 (3H, t,, J =
7.6 Hz), 1.86ꢀ1.92 (12H, m), 2.23 (3H, s), 3.24 (3H, s), 3.48 (3H, s),
3.69ꢀ3.84 (2H, m), 3.89ꢀ4.09 (6H, m), 9.71 (1H, s), 9.79 (1H, s),
10.29 (1H, s), 10.44 (1H, s); HRMS (ESI) calcd for C35H41N3O3 + H
552.3226, found 552.3228.
8,13,14,19-Tetraethyl-3,4-dihydro-3-hydroxy-3,9,18-tri-
methyl-4-oxo-2-oxybenziporphyrinatosilver(III) (30). Silver
acetate (10.0 mg, 0.060 mmol) was added to a stirred solution of 24
(10.0 mg, 0.019 mmol) in dichloromethane (10 mL) and methanol
(2.5 mL) and the mixture stirred overnight in a 25 mL round-bottom
flask fitted with a drying tube and protected from light with aluminum
foil. The resulting mixture was washed with water, back-extracting with
chloroform, and the solvent was removed under reduced pressure. The
dark red residue was chromatographed on flash silica eluting with 50%
dichloromethaneꢀchloroform to give the product as a dark orange
fraction. Recrystallization from chloroformꢀhexanes yielded the silver-
(III) complex (10.5 mg, 0.0167 mmol, 87%) as red crystals: mp
>300 °C; UVꢀvis (CHCl3) λmax (log10ε) 388 (4.49), 422 (4.83), 508
(3.91), 542 (4.23), 580 nm (4.02); 1H NMR (500 MHz, CDCl3) δ 1.66
(3H, s), 1.67ꢀ1.72 (12H, m), 3.32 (6H, s), 3.71ꢀ3.89 (8H, m), 4.80
(1H, s), 9.19 (2H, s), 9.91 (2H, s); 13C NMR (CDCl3) δ 12.1, 17.6, 18.3,
19.7, 20.1, 29.4, 82.7, 97.1, 111.8, 131.0, 134.90, 134.92, 136.5, 137.3,
141.1, 141.2, 199.7; HRMS (FAB) calcd for C33H34AgN3O3 + H
Crystallographic Experimental Details of 28b MeOH.
3
X-ray quality crystals for the methanol solvate of 28b were suspended
in mineral oil at ambient temperature, and a suitable crystal was selected.
A mineral oil coated black block thereby obtained of approximate dimen-
sions 0.70 ꢁ 0.51 ꢁ 0.43 mm3 was mounted on a 50 μm polyimide
micromount and transferred to a CCD-equipped X-ray diffractometer.
The X-ray diffraction data were collected at ꢀ173 °C using Mo KR
(λ = 0.71073 Å) radiation. Data collection and cell refinement were
performed using SMART and SAINT+, respectively.48 The unit cell
parameters were obtained from a least-squares refinement of 6734
628.1729, found 628.1728. Anal. Calcd for C33H34AgN3O3 1/8CHCl3:
3
centered reflections. Compound 28b MeOH was found to crystallize
C, 61.83; H, 5.34; N, 6.53. Found: C, 61.89; H, 5.30; N, 6.53.
3
in the monoclinic crystal system with the following unit cell parameters:
a = 9.3698(9) Å, b = 12.850(1) Å, c = 21.309(2) Å, β = 94.857(2)°, Z = 4.
The systematic absences indicated the space group to be P21/n
(no. 14).49 A total of 25832 reflections were collected, of which 6349
8,13,14,19-Tetraethyl-3,4-dihydro-3-hydroxy-3,9,18,23-
tetramethyl-4-oxo-2-oxybenziporphyrin (31a). Potassium car-
bonate (300 mg) and 10 drops of iodomethane were added to a solution
of 24 (29.7 mg, 0.057 mmol) in acetone (30 mL), and the resulting
mixture was stirred under reflux overnight. The mixture was diluted in
chloroform and washed with water, back-extracting with chloroform,
and the solvent removed under reduced pressure. The red residue was
chromatographed on flash silica eluting with 50% dichlorometha-
neꢀchloroform, and the product collected as a yellowish purple fraction.
The solvent was removed under reduced pressure to give the N-methyl
derivative (21.0 mg, 0.039 mmol, 70%) as a purple solid. The NMR
spectra indicate that the product consists of a mixture of two diastere-
omers in a ratio of approximately 2:1: UVꢀvis (Et3NꢀCHCl3) λmax (rel
int) 416 (1.00), 523 (0.12), 564 (0.11), 591 (0.10), 644 nm (0.05);
UVꢀvis (TFAꢀCHCl3) λmax (rel int) 405 (1.00), 418 (0.91), 525
(0.07), 563 (0.05), 578 nm (0.07); 1H NMR (major diastereomer, 500
MHz, CDCl3) δ ꢀ5.73 (1H, s), ꢀ4.54 (3H, s), ꢀ2.0 (1H, v br), 1.34
(3H, t, J = 7.7 Hz), 1.55 (3H, s), 1.77 (3H, t, J = 7.7 Hz), 1.86ꢀ1.91 (6H,
m), 3.18 (3H, s), 3.44 (3H, s), 3.70 (2H, q, J = 7.7 Hz), 3.88ꢀ4.07 (6H,
m), 9.62 (1H, s), 9.71 (1H, s), 10.52 (1H, s), 10.54 (1H, s); 1H NMR
(minor diastereomer, 500 MHz, CDCl3) δ ꢀ5.84 (1H, s), ꢀ4.71 (3H,
s), ꢀ2.0 (1H, v br), 1.40 (3H, t, J = 7.7 Hz), 1.81 (3H, t, J = 7.7 Hz),
1.88ꢀ1.92 (6H, m), 2.31 (3H, s), 3.24 (3H, s), 3.48 (3H, s), 3.76 (2H, q,
J = 7.7 Hz), 3.88ꢀ4.07 (6H, m), 9.69 (1H, s), 9.74 (1H, s), 10.18 (1H,
s), 10.47 (1H, s); HRMS (FAB) calcd for C34H39N3O3 + H 538.3070,
found 538.3069.
8,13,14,19,23-Pentaethyl-3,4-dihydro-3-hydroxy-3,9,18-
trimethyl-4-oxo-2-oxybenziporphyrin (31b). Potassium carbo-
nate (300 mg) and 10 drops of iodoethane were added to a solution of
24 (20.1 mg, 0.0384 mmol) in butanone (30 mL), and the resulting
mixture was stirred under reflux overnight. The mixture was diluted in
chloroform and washed with water, back-extracting with chloroform,
and the solvent removed under reduced pressure. The red residue was
purified by flash chromatography on silica eluting with 50% dichlor-
omethaneꢀchloroform, and the product collected as a yellowish-purple
fraction. The solvent was removed under reduced pressure to give the
N-ethyl derivative (14.2 mg, 0.0258 mmol, 67%) as a purple solid. The
NMR spectra indicate that the product consists of a mixture of two
2
were unique, and 5751 were observed Fo2 > 2 σ(Fo ). Limiting indices
were as follows: ꢀ12 e h e 12, ꢀ17 e k e 17, ꢀ28 e l e 28. Data
reduction were accomplished using SAINT.47 The data were corrected
for absorption using the SADABS procedure.49
Solution and data analysis were performed using the WinGX software
package.50 The structure of 28b MeOH was solved by charge-flipping
3
methods using the program SUPERFLIP,51 and the refinement was
completed using the program SHELX-97.52 All non-H atoms were
refined anisotropically. With the exception of the NH H atom, all H
atoms were included in the refinement in the riding-model approxima-
tion (CꢀH = 0.95, 0.98, and 0.99 Å for ArꢀH, CH3, and CH2; Uiso(H) =
1.2Ueq(C) except for methyl groups, where Uiso(H) = 1.5eq(C); OꢀH
= 0.84 Å; Uiso(H) = 1.5Ueq(O)) with CH3 and OH torsions taken from
electron density. The NH H atom was freely refined because it was
clearly visible in the difference Fourier map and placement in the
idealized riding model position would force it into space blocked by
the Se atom of the macrocycle. Full-matrix least-squares refinement on
F2 led to convergence, (Δ/σ)max = 0.000, (Δ/σ)mean = 0.0000, with R1 =
2
2
0.0275 and wR2 = 0.0757 for 6349 data with Fo > 2σ(Fo ) using 0
restraints and 346 parameters. A final difference Fourier synthesis
showed features in the range of ΔFmax = 0.65 eꢀ/Å3 to ΔFmin
=
ꢀ0.485 eꢀ/Å3, which were deemed of no chemical significance.
Molecular diagrams were generated using ORTEP-3.53 CCDC 826847
contains the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
’ ASSOCIATED CONTENT
S
Supporting Information. Crystallographic data for 28b
b
1
(CIF) and MS, UVꢀvis, IR, H NMR, COSY, HSQC, DEPT-
135, and 13C NMR spectra for selected compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
6306
dx.doi.org/10.1021/jo201098c |J. Org. Chem. 2011, 76, 6295–6308

The Journal of Organic Chemistry
ARTICLE
’ AUTHOR INFORMATION
(18) Graham, S. R.; Colby, D. A.; Lash, T. D. Angew. Chem., Int. Ed.
2002, 41, 1371–1374.
(19) Lash, T. D.; Colby, D. A.; Graham, S. R.; Chaney, S. T. J. Org.
Chem. 2004, 69, 8851–8864.
Corresponding Author
*E-mail: tdlash@ilstu.edu.
(20) Lash, T. D.; El-Beck, J. A.; Ferrence, G. M. J. Org. Chem. 2007,
72, 8402–8415.
Notes
†Conjugated Macrocycles Related to the Porphyrins. 58. For part
57, see ref 44d.
(21) For other syntheses of azuliporphyrins, see: (a) Lash, T. D.;
Chaney, S. T. Angew. Chem., Int. Ed. Engl. 1997, 36, 839–840. (b) Lash,
T. D. Chem. Commun. 1998, 1683–1684. (c) Venkatraman, S.; Anand,
V. G.; PrabhuRaja, V.; Rath, H.; Sankar, J.; Chandrashekar, T. K.; Teng,
W.; Senge, K. R. Chem. Commun. 2002, 1660–1661. (d) Colby, D. A.;
Ferrence, G. M.; Lash, T. D. Angew. Chem., Int. Ed. 2004, 43, 1346–1349.
(e) Okujima, T.; Komobuchi, N.; Shimizu, Y.; Uno, H.; Ono, N.
Tetrahedron Lett. 2004, 45, 5461–5464. (f) Lash, T. D.; Colby, D. A.;
Idate, A. S.; Davis, R. N. J. Am. Chem. Soc. 2007, 129, 13801–13802.
(g) Zhang, Z.; Ferrence, G. M.; Lash, T. D. Org. Lett. 2009, 11, 101–104.
(22) (a) Colby, D. A.; Lash, T. D. J. Org. Chem. 2002, 67, 1031–1033.
(b) Lash, T. D.; El-Beck, J. A.; Colby, D. A. J. Org. Chem. 2009,
74, 8830–8833.
(23) (a) Colby, D. A.; Lash, T. D. Chem.—Eur. J. 2002, 8,
5397–5402. (b) Lash, T. D.; Colby, D. A.; Ferrence, G. M. Eur. J. Org.
Chem. 2003, 4533–4548. (c) El-Beck, J. A.; Lash, T. D. Eur. J. Org. Chem.
2007, 3981–3190.
(24) For other applications of this concept, see: (a) Sprutta, N.;
Swiderska, M.; Latos-Grazynski, L. J. Am. Chem. Soc. 2005, 127, 13108–
13109. (b) Berlicka, A.; Sprutta, N.; Latos-Grazynski, L. Chem Commun.
2006, 3346–3348. (c) Sprutta, N.; Siczek, M.; Latos-Grazynski, L.;
Pawlicki, M.; Szterenberg, L.; Lis, T. J. Org. Chem. 2007, 72, 9501–9509.
(d) Shoji, T.; Higashi, J.; Ito, S.; Toyota, K.; Iwamoto, T.; Morita, N. Eur.
J. Org. Chem. 2009, 5948–5952. (e) Sprutta, N.; Mackowiak, S.; Kocik,
M.; Szterenberg, L.; Lis, T.; Latos-Grazynski, L. Angew. Chem., Int. Ed.
2009, 48, 3337–3341.
(25) Lash, T. D. Chem.—Eur. J. 1996, 2, 1197–1200.
(26) (a) Lin, Y.; Lash, T. D. Tetrahedron Lett. 1995, 36, 9441–
9444. (b) Boudif, A.; Momenteau, M. J. Chem. Soc., Perkin Trans. 1
1996, 1235–1241. (c) Sessler, J. L.; Genge, J. W.; Urbach, A.;
Sanson, P. Synlett 1996, 187–188. (d) Lash, T. D. J. Porphyrins
Phthalocyanines 1997, 1, 29–44. (e) Lash, T. D.; Chandrasekar, P.;
Osuma, A. T.; Chaney, S. T.; Spence, J. D. J. Org. Chem. 1998, 63,
8455–8469.
(27) Preliminary communication: Miyake, K.; Lash, T. D. Chem.
Commun. 2004, 178–179.
(28) Jackson, A. H.; Pandey, R. K.; Rao, K. N. R.; Roberts, E.
Tetrahedron Lett. 1985, 26, 793–796.
(29) (a) Clezy, P. S.; Liepa, A. J. Aust. J. Chem. 1970, 23, 2443–2459.
(b) Lash, T. D. Tetrahedron 1998, 54, 359–374.
’ ACKNOWLEDGMENT
This work was supported by the National Science Foundation
under Grant Nos. CHE-0616555 and 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. K.M. and L.X. thank Abbott Laboratories for
providing summer graduate fellowships. We also thank Youngs-
town State University Structure & Chemical Instrumentation
Facility’s Matthias Zeller for X-ray data collection. The diffract-
ometer was funded by NSF Grant No. 0087210, Ohio Board of
Regents Grant No. CAP-491, and YSU.
’ REFERENCES
(1) Berlin, K.; Breitmaier, E. Angew. Chem., Int. Ed. Engl. 1994,
33, 1246–1247.
(2) Lash, T. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2533–2535.
(3) (a) Lash, T .D.; Chaney, S. T.; Richter, D. T. J. Org. Chem. 1998,
63, 9076–9088. (b) Liu, D.; Lash, T. D. Chem. Commun. 2002, 2426–
2427. (c) Jiao, W.; Lash, T. D. J. Org. Chem. 2003, 68, 3896–3901.
(d) Liu, D.; Ferrence, G. M.; Lash, T. D. J. Org. Chem. 2004, 69, 6079–
6093.
(4) Stepien, M.; Latos-Grazynski, L. Acc. Chem. Res. 2005, 38, 88–98.
(5) Stepien, M.; Latos-Grazynski, L. Chem.—Eur. J. 2001, 7, 5113–
5117.
(6) Lash, T. D.; Yant, V. R. Tetrahedron 2009, 65, 9527–9535.
(7) (a) Stepien, M.; Latos-Grazynski, L.; Szterenberg, L.; Panek, J.;
Latajka, Z. J. Am. Chem. Soc. 2004, 126, 4566–4580. (b) Stepien, M.;
Latos-Grazynski, L. Org. Lett. 2003, 5, 3379–3381. (c) Hung, C.-H.;
Chang, F.-C.; Lin, C.-Y.; Rachlewicz, K.; Stepien, M.; Latos-Grazynski,
L.; Lee, G.-H.; Peng, S.-M. Inorg. Chem. 2004, 43, 4118–4120.
(d) Stepien, M.; Latos-Grazynski, L.; Szterenberg, L. Inorg. Chem.
2004, 43, 6654–6662.
(8) (a) Stepien, M.; Latos-Grazynski, L. J. Am. Chem. Soc. 2002,
124, 3838–3839. (b) Hung, C.-H.; Lin, C.-Y.; Lin, P.-Y.; Chen, Y.-J.
Tetrahedron Lett. 2004, 45, 129–132.
(9) (a) Chang, G.-F.; Kumar, A.; Ching, W.-M.; Chu, H.-W.; Hung,
C.-H. Chem. Asian J. 2009, 4, 164–173. (b) Huang, C.; Li, Y.; Yang, J.;
Cheng, N.; Liu, H.; Li, Y. Chem. Commun. 2010, 46, 3161–3163.
(10) Richter, D. T.; Lash, T. D. Tetrahedron 2001, 57, 3659–3673.
(11) Szymanski, J. T.; Lash, T. D. Tetrahedron Lett. 2003, 44,
8613–8616.
(30) Bromine readily oxidizes dipyrrylmethanes to conjugated di-
pyrromethenes. Presumably, bromine vapor also oxidizes the benzitri-
pyrranes to conjugated species.
(31) Tardieux, C.; Bolze, F.; Gros, C. P.; Guilard, R. Synthesis
1998, 267–268.
(32) (a) Lash, T. D.; Richter, D. T.; Shiner, C. M. J. Org. Chem. 1999,
64, 7973–7982. (b) Richter, D. T.; Lash, T. D. Tetrahedron Lett. 1999,
40, 6735–6738. (c) Richter, D. T.; Lash, T. D. J. Org. Chem. 2004,
69, 8842–8850.
(33) Medforth, C. J. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 5,
pp 1ꢀ80.
(12) Lash, T. D.; Szymanski, J. T.; Ferrence, G. M. J. Org. Chem.
2007, 72, 6481–6492.
(13) Lash, T. D.; Young, A. M.; Rasmussen, J. M.; Ferrence, G. M.
J. Org. Chem. 2011, 76, 5636–5651.
(34) Latos-Grazynski, L.; Pacholska, E.; Chmielewski, P. J.; Olmstead,
M. M.; Balch, A. L. Inorg. Chem. 1996, 35, 566–573.
(35) Pushpan, S. K.; Srinivasan, A.; Anand, V. R. G.; Chandrashekar,
T. K.; Subramanian, A. R.; Roy, R.; Sugiura, K.; Sakata, Y. J. Org. Chem.
2001, 66, 153–161.
(36) Mysliborski, R.; Latos-Grazynski Eur. J. Org. Chem. 2005,
5039–5048.
(37) Allen, F. H. Acta Crystallogr. 2002, B58, 380–388.
(38) Furuta, H.; Ogawa, T.; Uwatoko, Y.; Araki, K. Inorg. Chem.
1999, 38, 2676–2682.
(14) Venkatraman, S.; Anand, V. G.; Pushpan, S. K.; Sankar, J.;
Chandrashekar, T. K. Chem. Commun. 2002, 462–463.
(15) El-Beck, J. A.; Lash, T. D. Org. Lett. 2006, 8, 5263–5266.
(16) Lash, T. D. In The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 2, pp
125ꢀ199.
(17) (a) Lash, T. D. Synlett 2000, 279–295. (b) Lash, T. D. Eur. J.
Org. Chem. 2007, 5461–5481.
6307
dx.doi.org/10.1021/jo201098c |J. Org. Chem. 2011, 76, 6295–6308

The Journal of Organic Chemistry
ARTICLE
(39) Lash, T. D.; Rasmussen, J. M.; Bergman, K. M.; Colby, D. A.
Org. Lett. 2004, 6, 549–552.
(40) (a) Muckey, M. A.; Szczepura, L. F.; Ferrence, G. M.; Lash,
T. D. Inorg. Chem. 2002, 41, 4840–4842. (b) Lash, T. D.; Colby, D. A.;
Szczepura, L. F. Inorg. Chem. 2004, 43, 5258–5267.
(41) Bergman, K. M.; Ferrence, G. M.; Lash, T. D. J. Org. Chem.
2004, 69, 7888–7897.
(42) N-Confused porphyrins can also act as dianionic ligands and
may take on more complex coordination motifs. See: (a) Latos-
Grazynski, L. In The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 2, pp
361ꢀ416. (b) Srinivasan, A.; Furuta, H. Acc. Chem. Res. 2005,
38, 10–20. (c) Harvey, J. D.; Ziegler, C. J. Coord. Chem. Rev. 2003,
247, 1–19.
(43) Benziporphyrins commonly act as dianionic ligands.7 In addi-
tion, oxybenziporphyrin can also act as a dianionic ligand as well.
Stepien, M.; Latos-Grazynski, L.; Lash, T. D.; Szterenberg, L. Inorg.
Chem. 2001, 40, 6892–6900.
(44) For other examples of organometallic derivatives of carbapor-
phyrinoid systems, see: (a) Graham, S. R.; Ferrence, G. M.; Lash, T. D.
Chem. Commun. 2002, 894–895. (b) Lash, T. D.; Colby, D. A.; Graham,
S. R.; Ferrence, G. M.; Szczepura, L. F. Inorg. Chem. 2003,
42, 7326–7338. (c) Lash, T. D.; Young, A. M.; Von Ruden, A. L.;
Ferrence, G. M. Chem. Commun. 2008, 6309–6311.(d) Young, A. M.;
Von Ruden, A. L.; Lash, T. D. Org. Biomol. Chem. 2011, DOI:10.1039/
C1OB05603D. (e) Lash, T. D. Macroheterocycles 2008, 1, 9–20.
(45) (a) Daniell, H. W.; Br€uckner, C. Angew. Chem., Int. Ed. 2004,
43, 1688–1691. (b) Chmielewski, P. J.; Szterenberg, L.; Siczek, M.
Chem.—Eur. J. 2011, 17, 1009–1020.
(46) Tripyrrane analogues 20a and 20b were also used to prepare
dicarbaporphyrinoid systems: See, Xu, L.; Lash, T. D. Tetrahedron Lett.
2006, 47, 8863–8866.
(47) Johnson, A. W.; Kay, I. T.; Markham, E.; Price, R.; Shaw, K. B.
J. Chem. Soc. 1959, 3416–3424.
(48) APEX2 v2008.2ꢀ4, Bruker AXS, Inc., Madison, WI, 2008.
(49) McArdle, P. J. Appl. Crystallogr. 1996, 29, 306.
(50) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–838.
(51) Palatinus, L.; Chapuis, G. J. Appl. Crystallogr. 2007, 40,
786–790.
(52) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112–122.
(53) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
6308
dx.doi.org/10.1021/jo201098c |J. Org. Chem. 2011, 76, 6295–6308