Synthesis of indenoporphyrins, highly modified porphyrins with reduced diatropic characteristics

Article abstract of DOI:10.1021/jo2006895

Indene-fused porphyrins have been synthesized starting from 2-indanone. Knorr-type reaction of oximes derived from benzyl or tert-butyl acetoacetate with 2-indanone and zinc dust in propionic acid gave good yields of indenopyrroles. Treatment with N-chlorosuccinimide then gave 8-chloro derivatives, and these reacted with 5-unsubstituted pyrroles to give dipyrroles incorporating the fused indene unit. Hydrogenolysis of the benzyl ester protective groups afforded the related dicarboxylic acids, but condensation with a dipyrrylmethane dialdehyde under MacDonald "2 + 2" reaction conditions gave poor yields of the targeted indenoporphyrins. However, when an indene-fused dipyrrole was converted into the corresponding dialdehyde with TFA-trimethyl orthoformate and then reacted with a dipyrrylmethane dicarboxylic acid, an indenoporphyrin was isolated in 26% yield. The porphyrin gave a highly modified UV-vis absorption spectrum with three strong bands showing up in the Soret region and a series of Q bands that extended beyond 700 nm. The proton NMR spectrum also showed a significantly reduced diamagnetic ring current where the meso-protons gave resonances near 9.3 ppm instead of typical porphyrin values of 10 ppm. Nickel(II), copper(II), and zinc complexes were also prepared, and these exhibited unusual UV-vis absorption spectra with bathochromically shifted Soret and Q absorptions. The diamagnetic nickel(II) and zinc complexes also showed reduced diatropic character compared to typical nickel(II) and zinc porphyrins.

Full text of DOI:10.1021/jo2006895

ARTICLE
pubs.acs.org/joc
Synthesis of Indenoporphyrins, Highly Modified Porphyrins with
Reduced Diatropic Characteristics†
Timothy D. Lash,* Breland E. Smith, Michael J. Melquist, and Bradley A. Godfrey
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, United States
S Supporting Information
b
ABSTRACT: Indene-fused porphyrins have been synthesized
starting from 2-indanone. Knorr-type reaction of oximes derived
from benzyl or tert-butyl acetoacetate with 2-indanone and zinc
dust in propionic acid gave good yields of indenopyrroles.
Treatment with N-chlorosuccinimide then gave 8-chloro deriva-
tives, and these reacted with 5-unsubstituted pyrroles to give
dipyrroles incorporating the fused indene unit. Hydrogenolysis of
the benzyl ester protective groups afforded the related dicar-
boxylic acids, but condensation with a dipyrrylmethane dialde-
hyde under MacDonald “2 þ 2” reaction conditions gave poor
yields of the targeted indenoporphyrins. However, when an
indene-fused dipyrrole was converted into the corresponding
dialdehyde with TFAꢀtrimethyl orthoformate and then reacted with a dipyrrylmethane dicarboxylic acid, an indenoporphyrin
was isolated in 26% yield. The porphyrin gave a highly modified UVꢀvis absorption spectrum with three strong bands showing up in
the Soret region and a series of Q bands that extended beyond 700 nm. The proton NMR spectrum also showed a significantly
reduced diamagnetic ring current where the meso-protons gave resonances near 9.3 ppm instead of typical porphyrin values of
10 ppm. Nickel(II), copper(II), and zinc complexes were also prepared, and these exhibited unusual UVꢀvis absorption spectra
with bathochromically shifted Soret and Q absorptions. The diamagnetic nickel(II) and zinc complexes also showed reduced
diatropic character compared to typical nickel(II) and zinc porphyrins.
’ INTRODUCTION
Fusion of aromatic units to the pyrrole rings in porphyrins can
give rise to highly red-shifted chromophores,1,2,6ꢀ13 but this is
not always the case. For instance, phenanthroporphyrins (e.g., 1)
only show minor bathochromic shifts due to the presence of the
fused tricyclic unit,9 whereas structurally similar acenaphthylene-
fused porphyrins 2 have considerably modified absorption
bands.11,14 Modification of the porphyrin system by cyclization
onto the meso-positions can also produce unusual porphyrinoid
chromophores.15,16 Substantial efforts have been put into the
synthesis of this type of system from tetraarylporphyrins, and
these investigations commonly afford six-membered ring sys-
tems such as 3.15,16 The formation of fused five-membered ring
structures such as 4 has also been noted, initially as minor
byproducts.15 These types of indene-fused systems are intriguing
as they show highly modified UVꢀvis absorptions. Fox and
Boyle reported a synthesis of metalated indenoporphyrins 5 by
reacting nickel(II) or copper(II) 2-iodophenylporphyrins 6 with
Pd(PPh3)4 and potassium phosphate (Scheme 1).17 An alter-
native route was subsequently developed where nickel(II),
copper(II), zinc, or free base 2-bromo tetraphenylporphyrins 8
were cyclized using Pd2(dba)3 and potassium carbonate
(Scheme 1).18 This ring closure can also be accomplished by
the zinc-mediated cyclization of tetrarylporphyrin radicals.19 The
Extended porphyrinoid chromophores have been widely
investigated1,2 because of their potential to produce long wave-
length absorptions that could make them suitable for applications
as photosensitizers in photodynamic therapy,3 as biological
sensors,4 or in the development of novel optical materials.5
Received: April 1, 2011
Published: May 20, 2011
r
2011 American Chemical Society
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Scheme 1
Scheme 3
Scheme 4
Scheme 2
cyclohexadecanone worked well only at temperatures >140 °C
in propionic acid.26i Cyclopentanone gave good yields of
cyclopenta[b]pyrroles only when the temperature was maintained
at >150 °C in a mixture of sodium propionate and propionic
acid.25b Multigram quantities of cycloalka[b]pyrroles are easily
prepared by this approach, and these heterocycles are the key
intermediates in the synthesis of cycloalkanoporphyrins like 8
and 9.24ꢀ26
In principle, the synthesis of indenoporphyrins 14 could be
approached in a similar fashion. A retrosynthetic analysis of
14 shows that this system could be obtained by using the
MacDonald “2 þ 2” methodology33,34 from dipyrrylmethane
dialdehyde 15 and the indene fused dipyrrole 16 (Scheme 3).
Dipyrrole 16, in turn, could be prepared from the indenopyrrole
17. The successful application of this strategy and the spectro-
scopic properties of the resulting indenoporphyrins are pre-
sented below.35
formation of 5 by the intramolecular Heck reaction of a tetra-
phenylporphyrin boronic ester has been noted,20ꢀ22 and the
preparation of more complex porphyrin systems that incorporate
a fused indene unit have also been described.23 We have
developed versatile routes to cycloalkanoporphyrins (CAPs),
including the porphyrin molecular fossils deoxophylloerythroe-
tioporphyrin (DPEP, 8) and butanoporphyrin 9, starting from
cyclic ketones.24ꢀ26 CAPs are commonly found in petroleum
and oil shales as their nickel(II) or vanadyl complexes,27 and
synthetic samples have been used to develop spectroscopic,28
mass spectrometric,29 and chromatographic methods30 for the
analysis of these materials. Cyclic ketones 10 were shown to react
with oximes 11 or phenylhydrazones 12 in the presence of zinc
dust and acetic or propionic acid to give the cycloalka[b]pyrroles
13 in good yields (Scheme 2).24ꢀ26,31 In this variation on the
Knorr pyrrole reaction,32 an R-amino ketone is generated in situ
and reacts with ketones 10 to afford pyrroles 13 (Scheme 2).
Optimal yields are somewhat temperature-dependent, and
syntheses using large ring ketones such as cyclododecanone or
’ RESULTS AND DISCUSSION
The synthesis of indenoporphyrins 14 required the availability
of indenopyrroles 17. In fact, an example of an indenopyrrole 17a
had been reported previously.25b Reaction of the oxime 11a
derived from ethyl acetoacetate with 2-indanone in propionic
acid containing sodium propionate at 150 °C gave the indeno-
pyrrole in 34% yield (Scheme 4).25b The corresponding benzyl
ester 17b was prepared similarly from oxime 11b and 2-indanone
in 47% yield. However, the related tert-butyl ester 17c was
obtained in very low yields under these conditions. Following a
series of attempts, the yield was raised to 33% when the oxime
and zinc dust were added to 2-indanone and sodium propionate
in propionic acid at 140 °C and the reaction was stopped after
5 min once the addition had been completed. The same approach
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Scheme 5
Scheme 7
with this reagent. Dihydrobenzoindoles 18 were also reacted
with lead tetraacetate, but in this case the corresponding benzo-
[e]indoles 19 were formed (Scheme 5). Reaction of 18 with
Pb(OAc)4 would be expected to give the acetoxy-derivatives 20,
but these spontaneously eliminate acetic acid to give the fully
conjugated tricycles 19. This chemistry provides a useful route to
benzo[e]indoles but cannot be applied to porphyrin synthesis. In
an alternative strategy, 17b was reacted with N-chlorosuccini-
mide (NCS) in carbon tetrachloride (Scheme 6). Under these
conditions, benzyl ester 17b underwent selective chlorination to
give the 8-chloroindenopyrrole 21a, and following recrystalliza-
tion from toluene the derivative was isolated in 63% yield.
The formation of dipyrrolic products from 21a required the
availability of R-unsubstituted pyrroles 22aꢀc. Pyrroles 22a and
22c are known compounds and may be prepared by modification
of the related 5-methylpyrroles36 or by using the Bartonꢀ-Zard
reaction.37,38 The necessary nitroalkane precursor to 4-butylpyr-
role 22b using the latter methodology is not readily available, and
so this R-unsubstituted pyrrole was prepared from 5-methylpyr-
role 23 (Scheme 7). Reaction with 3.3 equiv of sulfuryl chloride,
followed by hydrolysis with sodium acetate in aqueous dioxane,
gave carboxylic acid 24 in 40% yield. Iodinative decarboxylation
with I2/KI gave iodopyrrole 25 and subsequent hydrogenolysis
over Adam’s catalyst then gave the required R-free pyrrole 22b.
Chlorinated indenopyrrole 21a was reacted with R-unsubsti-
tuted pyrroles 22aꢀc in acetic acid at room temperature, using
p-toluenesulfonic acid as a catalyst, to give dipyrroles 26aꢀc in
40ꢀ66% yield (Scheme 6). A mixed ester dipyrrole 26d was also
prepared. Reaction of NCS with indenopyrrole tert-butyl ester
17c gave poor results due to the instability of the chlorinated
product 21b. The crude product from this reaction was imme-
diately reacted with 22a in the presence of p-toluenesulfonic acid
in acetic acid, but dipyrrole 26d could only be isolated in 21%
yield. Due to these low yields, the mixed ester dipyrrole 26d was
not further investigated.
Scheme 6
The 1H NMR spectra for indenodipyrrole 26a in CDCl3 and
DMSO-d6 indicate that solvent interactions can cause significant
conformational changes. In CDCl3, the ethyl substituent gives
rise to a quartet and a triplet at 2.49 and 1.10 ppm, respectively,
which fall into the expected range of a typical pyrrolic ethyl
group. This coupling indicates that free rotation of the ethyl
substituent occurs and that both protons for the potentially
diastereotopic CH2 unit have identical chemical shift values.
However, in DMSO-d6 the peaks associated with this CH2 group
give rise to two 1H multiplets centered on 1.47 and 1.56 ppm.
Furthermore, the CH3 group for the ethyl moiety is shifted
upfield to 0.27 ppm (Figure 1). These signals suggest that a single
was also used to prepare dihydrobenzo[e]indoles 18a and 18b
from 2-tetralone, although in this case phenylhydrazones 12 gave
better results than oximes 11 (Scheme 5). Again, high tempera-
ture conditions (>150 °C) were required to get the best results,
and 8,9-dihydrobenzo[e]indoles 18 were formed in up to
65% yield.
In order to generate dipyrrolic intermediates from indenopyr-
roles 17, it was necessary tointroduce a suitableleaving grouponto
the five-membered carbocyclic ring. This had been accomplished
for cycloalka[b]pyrroles 13 using lead tetraacetate,24ꢀ26,31 but no
stable product could be isolated from the reaction of pyrroles 17
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Scheme 8
Figure 1. Partial 500 MHz proton NMR spectrum of dipyrrole 26a in
DMSO-d6 showing the atypically upfield shifted resonances for the
ethyl unit.
dipyrrylmethane 28.41 Dicarboxylic acid 16a was decarboxylated
with trifluoroacetic acid and then treated with trimethyl
orthoformate to produce dialdehyde 27 (Scheme 6). Initially,
trimethyl orthoformate was added at temperatures <0 °C and the
reagents allowed to react at room temperature for 15 min, and
this gave the dialdehyde in 33% yield. However, after a series of
attempts the yield was raised to 81% when trimethyl orthofor-
mate was introduced at temperatures between 20 and 25 °C, and
the reaction was then allowed to proceed afterward for 10 min at
40 °C. The proton NMR spectra for 16 and 27 in DMSO-d6 gave
results similar to those with 26a, showing that the ethyl group
was held over the fused benzene ring, although the ethyl
resonances for dialdehyde 27 were broadened. The carbon-13
NMR spectrum of 27 in DMSO-d6 also showed broadened
peaks, presumably due to hindered rotation for the alkyl sub-
stituent (see Supporting Information). Dialdehyde 27 was
reacted with dipyrrole dicarboxylic acid 28 using the slow
addition MacDonald “2 þ 2” conditions described above
(Scheme 8). The initial condensation gives rise to a porphodi-
methene intermediate 29, but subsequent treatment with zinc
acetate and air oxidation gave the indenoporphyrin. Following
purification by column chromatography on neutral alumina and
recrystallization from chloroformꢀmethanol, indenoporphyrin
14a was isolated as a dark green solid in 26% yield (Scheme 8).
As anticipated, the spectroscopic properties of this system are
quite unusual and differ considerably from typical porphyrins.
The UVꢀvis absorption spectra of 14 gave rise to a very distorted
electronic absorption spectrum with no distinct Soret band, and
instead three moderately intense absorption maxima are seen
between 400 and 500 nm (Figure 3). Addition of TFA gives a
Figure 2. Proposed conformation for dipyrroles 16, 26, and 27 in
DMSO-d6.
conformation is favored in DMSO that results in restricted
rotation of the ethyl substituent (Figure 2). It is postulated that
DMSO is able to stabilize this conformation by hydrogen
bonding to both pyrrolic NHs and that the pyrrole ring is
oriented so that it causes the CH3 of the ethyl group to be
located over the benzene ring thereby leading to the observed
shielding effect. This also causes an upfield shift to the CH2
resonances and provides an environment that strongly differ-
entiates between the diastereotopic protons. Conformational
factors of this type can have a significant impact on macrocyclic
ring formation.26j,39
Dipyrrole 26c was poorly soluble in organic solvents and
could not be deprotected. However, dipyrrole dibenzyl esters
26a and 26b were converted in quantitative yields into the related
dicarboxylic acid 16 by hydrogenolysis over 10% palladiumꢀ
charcoal. Dipyrroles 16a and 16b were reacted with dipyrryl-
methane dialdehyde 15 in the presence of p-toluenesulfonic acid,
followed by the addition of excess zinc acetate and air oxidation,
but no more than trace amounts of porphyrins 14 were generated
(Scheme 8). The reactions were repeated by adding a mixture of
15 and 16 to a solution of p-toluenesulfonic acid in metha-
nolꢀdichloromethane over a period of 2 h. This method allows
the concentration of reactants at any given moment to approx-
imate to high dilution conditions that should aid in macrocycle
formation,40 but the targeted porphyrins could still only be
isolated in 6ꢀ7% yield.
2þ
diprotonated species 14H2 where the UVꢀvis spectrum is
more porphyrin-like showing a Soret band at 434 nm with
atypically broad peaks on either side (Figure 3). In addition,
the modified chromophore gives rise to bathochromic shifts for
both species pushing the absorbance wavelengths of the Q bands
into the far red region. The chemical shifts in the proton NMR
An alternative “2 þ 2” condensation can be carried out with a
dialdehyde 27 derived from the indene-fused dipyrrole and
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Figure 3. UVꢀvis spectra of indenoporphyrin 14a in chloroform
(green line) and 1% TFAꢀchloroform (dication 14aH22þ, blue line).
Figure 5. UVꢀvis spectra of nickel(II) indenoporphyrin 30a (green
line) and copper complex 30b (purple line) in chloroform.
DPEP (8) and related porphyrins) does not significantly affect
the diatropic character of the porphyrin macrocycle.24,25
Indenoporphyrin 14a was reacted with metal acetates in
refluxing chloroformꢀmethanol to give the corresponding
nickel(II), copper(II), or zinc porphyrins 30aꢀc in excellent
yields (Scheme 8). The proton NMR spectrum of nickel(II)
complex 30a shows that it has a slightly smaller diatropic ring
current than the free base porphyrin 14a, with the meso-protons
appearing between 8.99 and 9.16 ppm. The methyl resonances
were also shifted upfield to between 3.18 and 3.23 ppm. The
decreased diatropicity of 30a is attributed to the presence of a
small nickel cation which causes the porphyrin macrocycle to
distort or ruffle to allow optimal complexation.43 The UVꢀvis
spectrum for 30a showed a Soret band at 427 nm and a series of
Q bands that extended beyond 700 nm (Figure 5). Copper(II)
porphyrins are paramagnetic and copper complex 30b could not
be characterized by NMR spectroscopy. The UVꢀvis spectrum
for 30b was similar to 30a but showed two strong Soret bands
near 450 nm (Figure 5). Porphyrins 14 and metallo-derivatives
30aꢀc were all further characterized by mass spectrometry.
TLC on silica plates indicated that the zinc complex 30c is
more polar than the nickel or copper complexes 30a and 30b.
Because of the poor solubility of the zinc complex in chloroform,
difficulties were encountered in obtaining high quality proton
NMR spectra. The zinc complex did dissolve to a limited extent
and chemical shift values could be obtained. Addition of one drop
of pyrrolidine greatly increased the solubility of the metallopor-
phyrin. Pyrrolidine forms an adduct with the zinc complex,
disrupting porphyrin aggregation and thereby increasing solubi-
lity, making it easier to obtain NMR spectra. However, no
significant changes in the chemical shifts were noted. The
meso-protons of the zinc complex, with or without pyrrolidine,
appear between 9.21 and 9.42 ppm, which is slightly downfield
compared to the free base indenoporphyrin 14a but upfield
compared to typical zinc porphyrins. The UVꢀvis spectrum for
zinc complex 30c in chloroform gave a broad Soret band at
459 nm with a smaller broad absorption at 436 nm and Q-band
absorptions extending into the far red region (Figure 6). All three
metal complexes show two Soret absorptions, but in the nickel
complex the lower wavelength absorption dominates, while both
bands have comparable intensities for the copper complex and
the longer wavelength band dominates for the zinc complex. In
addition, the absorption bands shift to higher wavelengths going
to higher atomic number (nickel to copper to zinc) as is observed
for regular porphyrins.2,44 Addition of pyrrolidine to solutions of
30c in chloroform gives rise to further bathochromic shifts and an
Figure 4. 500 MHz proton NMR spectrum of indenoporphyrin 14a in
CDCl3.
spectra of 14 indicate that the system has somewhat compro-
mised aromatic character. The meso-protons of the free base
appear as three singlets between 9.12 and 9.35 ppm, while the
internal NHs give rise to two broad singlets between ꢀ1.22 and
0 ppm (Figure 4). These NH resonances are downfield compared
to a typical aromatic porphyrin in which the internal NH protons
appear between ꢀ3 and ꢀ4 ppm, while the meso-protons have
been shifted upfield from a typical value of þ10 ppm.42 The
methyl substituents for porphyrins commonly show up near
3.6 ppm,42 but for 14a these substituents gave rise to four upfield
singlets at 3.21, 3.27. 3.34 and 3.38 ppm. These shifts indicate
that the indenoporphyrin has significantly reduced diatropic
2þ
character. The corresponding porphyrin dication 14H2 can
be generated in TFAꢀCDCl3 and gives chemical shifts near
10 ppm for the external protons while the internal NHs show up
at ꢀ1.74 and ꢀ0.97 ppm. These results suggest that protonation
leads to a slight increase in the diamagnetic ring current, although
these shifts are still not as large as those seen for typical porphyrin
dications. The reduced aromaticity of this system is most likely
due to unfavorable angle strain due to indene moiety, where all
5 carbons of the fused five-membered ring are sp2 hybrid-
ized. However, a fused five-membered ring by itself (e.g., for
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27 mmol) in propionic acid (112 mL) was then added dropwise,
simultaneously adding zinc dust (10 g) in small portions, while main-
taining the reaction temperature at 140 °C. Once the addition was
complete, the resulting mixture was allowed to stir for 5 min while
maintaining the temperature at 140 °C and then poured into a beaker of
ice water (750 mL) and allowed to stand for 2 h. The mixture was
filtered, and the solid was dissolved in dichloromethane and washed with
water. The residue was chromatographed on a silica column, eluting with
a 50:50 mixture of chloroform and hexanes. The product fractions were
identified by TLC and evaporated. Recrystallization from ethanol gave
the indenopyrrole (2.23 g, 8.29 mmol, 33%) as off-white crystals, mp
201ꢀ202 °C. IR (nujol) ν 3302 (NH str.), 1663 cmꢀ1 (CdO str.); 1H
NMR (500 MHz, CDCl3) δ 1.65 (9H, s), 2.60 (3H, s), 3.61 (2H, s), 7.11
(1H, td, J = 1.1, 7.5 Hz), 7.29 (1H, t, J = 7.5 Hz), 7.39 (1H, d, J = 7.5 Hz),
7.53 (1H, d, J = 7.5 Hz), 9.63 (1H, br s); 13C NMR (CDCl3) δ 11.9,
28.8, 30.7, 80.8, 118.9, 120.7, 123.6, 124.0, 125.2, 127.1, 130.7, 139.8,
141.9, 143.3, 162.2. Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N,
5.20. Found: C, 75.57; H, 7.13; N, 5.25.
Figure 6. UVꢀvis spectra of zinc indenoporphyrin 30c in chloroform
(blue line) and 1% pyrrolidineꢀchloroform (pink line).
intensification of the Soret band (Figure 6). The Soret band is
now observed at 470 nm and the Q bands extend to 768 nm.
Ethyl 3-Methyl-7,8-dihydrobenzo[f]indole-2-carboxylate
(18a). A stirred mixture of 2-tetralone (3.65 g, 25.0 mmol), sodium
propanoate (33.6 g) and propionic acid (112 mL) was heated to 150 °C.
A solution of phenylhydrazone 12a31 (5.85 g, 25 mmol) in propionic
acid (112 mL) was then added dropwise, while simultaneously adding
zinc dust (10 g) in small portions, maintaining the reaction mixture at a
temperature between 150 and 155 °C. Once the addition was complete,
the resulting mixture was allowed to stir for 1 h while maintaining the
temperature between 120 and 130 °C. The resulting mixture was cooled
to 70 °C, poured into a beaker of ice water (1.0 L), and allowed to stand
overnight. The precipitate was filtered, and the solid recrystallized from
ethanol to give the dihydrobenzoindole (4.14 g, 65%) as an off-white
powder, mp 188ꢀ189 °C. IR (nujol) ν 3278 (NH str.), 1660 cmꢀ1
(CdO str.); 1H NMR (500 MHz, CDCl3) δ 1.40 (3H, t, J = 7.1 Hz),
2.68 (3H, s), 2.80 (2H, t, J = 7.5 Hz), 2.97 (2H, t, J = 7.5 Hz), 4.36 (2H, q,
J = 7.1 Hz), 7.09 (1H, dt, J = 1.2, 7.4 Hz), 7.21ꢀ7.24 (1H, m), 7.25ꢀ7.27
(1H, m), 7.61 (1H, dd, J = 0.8, 7.7 Hz), 9.04 (1H, br s); 13C NMR
(CDCl3) δ 12.6, 14.8, 22.2, 30.1, 60.1, 118.5, 119.5, 123.0, 124.8, 125.1,
127.0, 128.4, 133.5, 134.3, 134.8, 162.2. Anal. Calcd for C16H17NO2: C,
75.27; H, 6.71; N, 5.49. Found: C, 75.08; H, 6.68; N, 5.37.
’ CONCLUSIONS
A synthesis of meso-unsubstituted indenoporphyrins has been
developed starting from 2-indanone. Following the formation of
indenopyrroles, dipyrroles incorporating a fused indene unit can
be generated in two steps and further transformed into a
dialdehyde. MacDonald “2 þ 2” condensation of the dialdehyde
with a dipyrrylmethane dicarboxylic acid then gave an indeno-
porphyrin in 26% yield. The UVꢀvis spectra for indenoporphyr-
ins are unusual, showing multiple bands in the Soret region and
Q-band absorptions that extend into the far red. The proton
NMR spectra for indenoporphyrins also show that the diamag-
netic ring current for this porphyrin system is significantly
reduced. Metalated derivatives show similarly modified charac-
teristics. Hence, this system provides some insights into the
aromatic characteristics of porphyrins and the novel optical
properties of indenoporphyrins may lead to applications as
photosensitizers or in the development of new optical materials.
Benzyl 3-Methyl-7,8-dihydrobenzo[f]indole-2-carboxylate
(18b). Following the same procedure, tetralone (3.65 g, 25.0 mmol)
was reacted with phenylhydrazone 12b26f (7.40 g, 25.0 mmol). Recrys-
tallization from ethanol gave the benzyl ester (4.90 g, 15.5 mmol, 62%)
as an off-white solid, mp 134ꢀ135 °C. IR (nujol) ν 3289 (NH str.),
1655 cmꢀ1 (CdO str.); 1H NMR (500 MHz, CDCl3) δ 2.73 (3H, s),
2.79 (2H, t, J = 7.5 Hz), 2.98 (2H, t, J = 7.5 Hz), 5.38 (2H, s), 7.13 (1H,
dt, J = 1.2, 7.5 Hz), 7.23ꢀ7.30 (2H, m), 7.36ꢀ7.40 (1H, m), 7.41ꢀ7.45
(2H, m), 7.47ꢀ7.50 (2H, m), 7.64 (1H, d, J = 7.6 Hz), 9.03 (1H, br s);
13C NMR (CDCl3) δ 12.7, 22.2, 30.0, 65.9, 118.1, 119.6, 123.1, 125.1,
125.4, 127.0, 128.4, 128.5, 128.8, 133.4, 134.3, 135.2, 136.7, 161.7. Anal.
Calcd for C21H19NO2: C, 79.47; H, 6.03; N, 4.41. Found: C, 79.37; H,
5.90; N, 4.20.
’ EXPERIMENTAL SECTION
Benzyl 3-Methylindeno[2,1-b]pyrrole-2-carboxylate (17b).
A stirred mixture of 2-indanone (6.60 g, 50.0 mmol), sodium propanoate
(67.2 g) and propionic acid (224 mL) was heated to 150 °C. A solution
of benzyl ester oxime 11b25b (12.15 g, 55 mmol) in propionic acid
(224 mL) was then added dropwise, simultaneously adding zinc dust (20 g)
in small portions, while maintaining the reaction mixture at a tempera-
ture between 150 and 155 °C. Once the addition was complete, the
resulting mixture was allowed to stir for 1 h while maintaining the
temperature between 150 and 155 °C. The resulting mixture was cooled
to 70 °C, poured into a beaker of ice water (1.5 L), and allowed to stand
overnight. The precipitate was filtered, and the solid recrystallized from
ethanol to give the indenopyrrole (7.155 g, 23.6 mmol, 47%) as a white
solid, mp 166ꢀ167 °C; IR (nujol) ν 3309 (NH str.), 1669 cmꢀ1 (CdO
str.); 1H NMR (500 MHz, CDCl3) δ 2.63 (3H, s), 3.61 (2H, s), 5.35
(2H, s), 7.11 (1H, td, J = 1.1, 7.5 Hz), 7.29 (1H, t, J = 7.5 Hz), 7.33ꢀ7.42
(5H, m), 7.44ꢀ7.47 (1H, m), 7.52 (1H, d, J = 7.5 Hz), 9.07 (1H, br s);
13C NMR (CDCl3) δ 11.9, 30.8, 65.9, 119.1, 122.1, 122.4, 123.9, 125.3,
127.2, 128.4, 128.8, 131.1, 136.6, 139.4, 142.6, 143.2, 161.8. Anal. Calcd
for C20H17NO2: C, 79.19; H, 5.65; N, 4.62. Found: C, 79.36; H, 5.50;
N, 4.72.
Ethyl 3-Methylbenzo[f]indole-2-carboxylate (19a). Lead
tetraacetate (95%, 0.93 g) was added to a stirred solution of 18a (0.515
g, 2.02 mmol) in dichloromethane (10 mL). The resulting solution was
stirred for 2 h at room temperature, then diluted with dichloro-
methane, washed with water, and dried over sodium sulfate. Recrys-
tallization from ethanol gave the benzo[f]indole (0.26 g, 1.03 mmol,
51%) as a light yellow powder, mp 179ꢀ180 °C. IR (nujol) ν 3308
1
(NH str.), 1666 cmꢀ1 (CdO str.); H NMR (500 MHz, CDCl3) δ
1.46 (3H, t, J = 7.1 Hz), 3.06 (3H, s), 4.45 (2H, q, J = 7.1 Hz),
7.44ꢀ7.48 (2H, m), 7.59ꢀ7.63 (1H, m), 7.69 (1H, d, J = 8.9 Hz), 7.91
(1H, d, J = 8.0 Hz), 8.54 (1H, d, J = 8.3 Hz), 9.09 (1H, br s); 13C NMR
(CDCl3) δ 13.5, 14.7, 60.8, 113.1, 121.7, 122.0, 123.0, 123.4, 123.8,
126.8, 127.7, 129.4, 130.1, 130.5, 133.7, 162.7. Anal. Calcd for
tert-Butyl 3-Methylindeno[2,1-b]pyrrole-2-carboxylate (17c).
A mixture of 2-indanone (3.30 g, 25.0 mmol) and sodium propanoate
(33.6 g) in propionic acid (112 mL) was prepared and heated while
stirring to 140 °C. A solution of tert-butyl ester oxime 11c25b (5.1 g,
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C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.83; H, 5.88;
N, 5.56.
below 10 °C. The resulting white precipitate was filtered, washed several
times with hot water, and dried under vacuum. Recrystallization from
ethanolꢀwater gave the carboxylic acid (4.45 g, 14.1 mmol, 40%) as a
white powder, mp 148 °C; 1H NMR (500 MHz, DMSO-d6) δ 0.87 (3H,
t, J = 7.3 Hz), 1.28 (2H, sextet, J = 7.5 Hz), 1.36ꢀ1.42 (2H, m), 2.19
(3H, s), 2.69 (2H, t, J = 7.6 Hz), 5.27 (2H, s), 7.31ꢀ7.35 (1H, m),
7.37ꢀ7.40 (2H, m), 7.37ꢀ7.40 (2H, m), 10.95 (1H, br s); 13C NMR
(DMSO-d6) δ 10.0, 13.9, 21.1, 22.0, 23.5, 32.7, 65.0, 119.1, 125.8, 126.0,
127.88, 127.90, 128.4, 129.0, 136.5, 160.4, 162.9. Anal. Calcd for
C18H21NO4: C, 68.55; H, 6.71; N, 4.44. Found: C, 68.20; H, 6.80;
N, 4.50.
Benzyl 3-Methylbenzo[f]indole-2-carboxylate (19b). Ben-
zyl ester 18b (0.634 g, 2.00 mmol) was reacted with lead tetraacetate
under the foregoing conditions. Recrystallization from ethanol gave the
title compound (0.30 g, 0.95 mmol, 48%) as a yellow powder, mp
178ꢀ180 °C. IR (nujol) ν 3303 (NH str.), 1669 cmꢀ1 (CdO str.); 1H
NMR (500 MHz, CDCl3) δ 3.08 (3H, s), 5.43 (2H, s), 7.36ꢀ7.40 (1H,
m), 7.41ꢀ7.51 (6H, m), 7.59ꢀ7.63 (1H, m), 7.69 (1H, d, J = 8.8 Hz),
7.91 (1H, d, J = 8.0 Hz), 8.53 (1H, d, J = 8.3 Hz), 9.10 (1H, br s); 13C
NMR (CDCl3) δ 13.6, 66.5, 113.1, 121.6, 121.7, 123.4, 123.6, 123.9,
126.9, 127.9, 128.6, 128.9, 129.4, 130.1, 130.4, 133.8, 136.2, 162.3. Anal.
Calcd for C21H17NO2: C, 79.98; H, 5.43; N, 4.44. Found: C, 79.61; H,
5.25; N, 4.35.
Benzyl 8-Chloro-3-methylindeno[2,1-b]pyrrole-2-carbox-
ylate (21a). Indenopyrrole 17b (3.60 g, 12 mmol) was dissolved in
carbon tetrachloride (287 mL), N-chlorosuccinimide (1.60 g, 12 mmol)
was added, and the solution was allowed to stir overnight under
anhydrous conditions. The resulting mixture was diluted with dichloro-
methane, washed with water and 5% aqueous sodium bicarbonate
solution, dried over sodium sulfate, and rotary evaporated. Recrystalliza-
tion from toluene afforded the chlorinated indenopyrrole (2.51 g, 7.44
mmol, 63%) as a fluffy yellow-orange solid, mp 160ꢀ161 °C, darkens at
134 °C. IR (nujol) ν 3266 (NH str.), 1672 cmꢀ1 (CdO str.); 1H NMR
(500 MHz, CDCl3) δ 2.56 (3H, s), 5.33ꢀ5.40 (2H, AB quartet, J = 12.3
Hz), 5.50 (1H, s), 7.16 (1H, td, J = 0.9, 7.5 Hz), 7.28ꢀ7.49 (8H, m), 9.28
(1H, br s); 13C NMR (CDCl3) δ 11.8, 50.6, 66.4, 119.6, 122.1, 124.4,
125.4, 125.9, 128.50, 128.54, 128.9, 129.6, 130.6, 136.3, 137.9, 140.9,
145.4, 161.5. Anal. Calcd for C20H16NO2Cl: C, 71.11; H, 4.77; N, 4.15.
Found: C, 70.67; H, 4.74; N, 4.20.
Benzyl 4-Butyl-5-iodo-3-methylpyrrole-2-carboxylate (25).
A solution of sodium bicarbonate (3.4 g) in water (35 mL) was added to
a solution of 5-benzyloxycarbonyl-4-methyl-3-butylpyrrole-2-carboxylic
acid (24) (4.00 g, 12.7 mmol) in methanol (35 mL), and the resulting
mixture heated on a water bath to 60 °C. A solution of iodine (3.3 g) and
potassium iodide (5.1 g) in water (135 mL) was added dropwise to the
stirred mixture over a period of 1 h, while maintaining the reaction
temperature at 60ꢀ65 °C, and stirring was continued for a further 1 h.
The mixture was cooled, and the precipitate filtered, washed well with
1% aqueous sodium thiosulfate solution to remove traces of iodine and
then with water. Recrystallization from ethanolꢀwater gave the iodo-
1
pyrrole (4.61 g, 91%) as a white powder, mp 107ꢀ108 °C; H NMR
(500 MHz, CDCl3) δ 0.93 (3H, t, J = 7.2 Hz), 1.30ꢀ1.44 (4H, m), 2.32
(3H, s), 2.35 (2H, t, J = 7.5 Hz), 5.30 (2H, s), 7.32ꢀ7.43 (5H, m), 8.83
(1H, s, br); 13C NMR (CDCl3) δ 11.2, 14.2, 22.6, 26.5, 32.6, 66.1, 73.6,
123.6, 127.4, 128.5, 128.8, 131.3, 136.4, 160.5. Anal. Calcd for
C17H20INO2: C, 51.14; H, 5.07; N, 3.52. Found: C, 51.29; H, 4.93;
N, 3.45.
Benzyl 4-Butyl-3-methylpyrrole-2-carboxylate (22b). Ben-
zyl 4-butyl-5-iodo-3-methylpyrrole-2-carboxylate (25) (4.00 g, 10.1
mmol), anhydrous sodium acetate (1.6 g), platinum oxide (24 mg),
and ethanol (160 mL) were placed in a hydrogenation vessel, and the
mixture was shaken under a hydrogen atmosphere at room temperature
and 30 psi for 24 h. The mixture was filtered to remove the catalyst, and
the solvent evaporated on a rotary evaporator. The residue was taken up
in chloroform, washed with water, dried over sodium sulfate, and
evaporated under reduced pressure to give the R-unsubstituted pyrrole
Benzyl 4-Butyl-3,5-dimethylpyrrole-2-carboxylate (23). A
solution of sodium benzyloxide was prepared by reacting sodium metal
(0.10 g) with benzyl alcohol (5 mL). Ethyl 4-butyl-3,5-dimethylpyrrole-
2-carboxylate45 (10.00 g; 44.8 mmol) in benzyl alcohol (10 mL) was
heated on an oil bath raised from room temperature to 230 °C over a
90 min period. The sodium benzyloxide was added in small amounts
periodically over the 90 min. When the vapor temperature above the
solution reached 200 °C, an additional 0.5 mL of sodium benzyloxide
solution was added, and the reaction continued for a further 5 min. The
hot solution was poured into a chilled mixture consisting of methanol
(32 mL), water (20 mL), and acetic acid (0.5 mL). The resulting
precipitate was collected by suction filtration and recrystallized from
95% ethanol to yield the benzyl ester (10.54 g, 37.0 mmol, 82%) as white
1
(2.70 g, 10.0 mmol, 99%) as a pale yellow oil; H NMR (500 MHz,
CDCl3) δ 0.95 (3H, t, J = 7.3 Hz), 1.35ꢀ1.42 (2H, m), 1.50ꢀ1.56
(2H, m), 2.32 (3H, s), 2.42 (2H, t, J = 7.7 Hz), 5.33 (2H, s), 6.68 (1H, d,
J = 2.9 Hz), 7.33ꢀ7.45 (5H, m), 8.75 (1H, s, br); 13C NMR (CDCl3) δ
10.6, 14.2, 22.7, 24.9, 32.7, 65.8, 119.1, 120.1, 126.3, 126.8, 128.30,
128.33, 128.8, 136.7, 161.6; HR MS (EI) calcd for C17H21NO2:
271.1572, found 271.1581.
1
crystals, mp 73ꢀ75 °C (lit. mp46 75ꢀ76 °C); H NMR (500 MHz,
CDCl3) δ 0.91 (3H, t, J = 7.2 Hz), 1.28ꢀ1.43 (4H, m), 2.18 (3H, s), 2.28
(3H, s), 2.35 (2H, t, J = 7.5 Hz), 5.29 (2H, s), 7.30ꢀ7.34 (1H, m),
7.35ꢀ7.39 (2H, m), 7.41ꢀ7.43 (2H, m), 8.56 (1H, s, br); 13C NMR
(CDCl3) δ 10.9, 11.8, 14.2, 22.7, 23.9, 33.3, 65.5, 116.5, 122.8, 128.2,
128.3, 128.7, 130.0, 136.9, 161.4. Anal. Calcd for C18H23NO2: C, 75.75;
H, 8.12; N, 4.91. Found: C, 75.75; H, 8.26; N, 5.01.
Benzyl 8(5-Benzyloxycarbonyl-3-ethyl-4-methyl-2-pyrrolyl)-
3-methylindeno[2,1-b]pyrrole-2-carboxylate (26a). A solution
of chlorinated indenopyrrole 21a (400 mg, 1.185 mmol), R-free pyrrole
22a38c (300 mg, 1.23 mmol), and p-toluenesulfonic acid (20 mg) in
glacial acetic acid (13 mL) was stirred for 2 h at room temperature. The
solution was diluted with dichloromethane, washed with water and 5%
aqueous sodium bicarbonate solution, dried over sodium sulfate, and
rotary evaporated to give a brown oil. The crude residue was purified by
column chromatography on silica, eluting with dichloromethane, and
the product fractions were identified by TLC, combined, and evapo-
rated. Recrystallization from toluene gave the indenodipyrrole (425 mg,
0.781 mmol, 66%) as a white solid, mp 200 °C, dec. IR (nujol) ν 3297,
3255 (NH str.), 1658 cmꢀ1 (CdO str.); 1H NMR (500 MHz, CDCl3) δ
1.10 (3H, t, J = 7.5 Hz), 2.30 (3H, s), 2.46ꢀ2.52 (2H, q, J = 7.5 Hz), 2.63
(3H, s), 4.95 (1H, s), 5.21 (2H, s), 5.25ꢀ5.35 (2H, AB quartet, J = 12.4
Hz), 7.07 (1H, td, J = 0.9, 7.5 Hz), 7.15 (1H, d, J = 7.5 Hz), 7.27ꢀ7.44
(11H, m), 7.52 (1H, d, J = 7.6 Hz), 8.14 (1H, br s), 8.88 (1H, br s); 1H
NMR (500 MHz, DMSO-d6) δ 0.27 (3H, t, J = 7.4 Hz), 1.41ꢀ1.51 (1H,
m), 1.51ꢀ1.61 (1H, m), 2.09 (3H, s), 2.54 (3H, s), 5.15 (1H, s),
5-Benzyloxycarbonyl-3-butyl-4-methylpyrrole-2-carboxylic
Acid (24). Freshly distilled sulfuryl chloride (9.3 mL, 15.4 g, 0.114 mol)
was added dropwise to a stirred solution of benzyl 3,5-dimethyl-4-
butylpyrrole-2-carboxylate (23) (10.00 g; 35.1 mmol) in ether (175 mL),
maintaining the temperature at 20 °C throughout. The resulting
solution was stirred for an additional 2 days at room temperature. The
ether was removed under reduced pressure, and the resulting orange oil
dissolved in dioxane (90 mL). A mixture of sodium acetate trihydrate
(35.0 g) in water (50 mL) was added to the solution, and the stirred
mixture heated at 70 °C for 1.5 h. The mixture was allowed to stand at
room temperature overnight. The mixture was extracted with ether (3 ꢁ
80 mL), and the combined ether layers extracted with sodium bicarbo-
nate solution (10%; 4 ꢁ 100 mL). The combined aqueous solution was
acidified with conc hydrochloric acid, while maintaining the temperature
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ARTICLE
5.23ꢀ5.33 (4H, m), 7.01 (1H, td, J = 0.9, 7.4 Hz), 7.06 (1H, d, J = 7.4
Hz), 7.23 (1H, d, J = 7.4 Hz), 7.29ꢀ7.50 (11H, m), 11.60 (1H, br s),
11.95 (1H, br s); 13C NMR (CDCl3) δ 10.9, 12.0, 16.4, 17.5, 40.0, 65.8,
66.1, 118.3, 119.5, 122.1, 123.0, 124.6, 125.1, 125.6, 127.1, 128.0, 128.13,
128.15, 128.31, 128.33, 128.6, 128.7, 129.5, 130.4, 136.3, 136.5, 138.6,
143.9, 146.5, 161.7, 161.9; HR MS (EI) calcd for C35H32N2O4:
544.2362, found 544.2366. Anal. Calcd for C35H32N2O4: C, 77.18; H,
5.92; N, 5.14. Found: C, 77.20; H, 5.82; N, 4.97.
146.3, 161.56, 161.60; HR MS (EI) calcd for C32H34N2O4: 510.2519,
found 510.2517. Anal. Calcd for C32H34N2O4 1/4H2O: C, 74.61; H,
3
6.75; N, 5.44. Found: C, 74.38; H, 6.87; N, 5.48.
8(5-Carboxy-3-ethyl-4-methyl-2-pyrrolyl)-3-methylindeno-
[2,1-b]pyrrole-2-carboxylic Acid (16a). Dibenzyl ester 26a (507.5
mg, 0.933 mmol), acetone (150 mL), methanol (20 mL), and triethy-
lamine (20 drops) was placed into a hydrogenation vessel. The air was
displaced with nitrogen, 10% palladium on activated carbon (150 mg)
was added, and the mixture was shaken at room temperature with
hydrogen at 30 psi for 16 h. The catalyst was removed by suction
filtration and evaporation of the solvent gave an oil. The residue was
dissolved in 5% aqueous ammonia and diluted with enough water was
added to give a total volume of 40 mL. The solution was cooled to less
than 5 °C, and acidified to litmus with glacial acetic acid while main-
taining the temperature below 5 °C, and then allowed to stand at <5 °C
for several hours. Suction filtration of the precipitate, followed by
vacuum desiccation, gave the dipyrrole dicarboxylic acid (338 mg,
Benzyl 8(5-Benzyloxycarbonyl-3,4-dimethyl-2-pyrrolyl)-
3-methylindeno[2,1-b]pyrrole-2-carboxylate (26c). Chlori-
nated indenopyrrole 21a (805 mg, 2.52 mmol), R-free pyrrole 22c38c
(600 mg, 2.62 mmol), and p-toluenesulfonic acid (20 mg) were reacted
under the foregoing conditions. Recrystallization from toluene gave the
indenodipyrrole (852 mg, 1.61 mmol, 64%) as a white solid, mp
217ꢀ218 °C, dec; 1H NMR (500 MHz, CDCl3) δ 2.04 (3H, s), 2.26
(3H, s), 2.62 (3H, s), 4.97 (1H, s), 5.09ꢀ5.32 (4H, m), 7.06 (1H, dt, J =
1.1, 7.5 Hz), 7.15 (1H, d, J = 7.7 Hz), 7.27ꢀ7.41 (11H, m), 7.51 (1H, d,
J = 7.5 Hz), 8.38 (1H, br s), 9.31 (1H, br s); 13C NMR (CDCl3) δ 9.2,
11.0, 12.0, 40.1, 65.8, 66.1, 118.1, 118.7, 119.5, 122.2, 123.2, 124.7, 125.1,
127.9, 128.1, 128.2, 128.4, 128.7, 128.8, 129.8, 130.6, 136.4, 136.6, 138.5,
143.4, 146.3, 161.6, 161.8; HR MS (EI) calcd for C34H30N2O4:
1
0.929 mmol, 99%) as a light purple solid, mp 133 °C, dec; H NMR
(500 MHz, DMSO-d6) δ 0.30 (3H, t, J = 7.5 Hz), 1.43ꢀ1.52 (1H, m),
1.53ꢀ1.62 (1H, m), 2.07 (3H, s), 2.52 (3H, s), 5.08 (1H, s), 6.99 (1H,
td, J = 0.8, 7.5 Hz), 7.06 (1H, d, J = 7.5 Hz), 7.21 (1H, t, J = 7.5 Hz), 7.45
530.2205, found 530.2200. Anal. Calcd for C34H30N2O4 1/5H2O: C,
(1H, d, J = 7.5 Hz), 11.34 (1H, s), 11.72 (1H, s), 11.91 (2H, br s); 13
C
3
76.44; H, 5.74; N, 5.24. Found: C, 76.27; H, 5.48; N, 5.00.
NMR (d6-DMSO) δ 10.1, 11.7, 14.6, 16.3, 40.5, 117.4, 118.4, 119.6,
122.2, 123.1, 123.7, 124.9, 125.9, 127.3, 128.5, 130.1, 138.3, 144.3, 147.5,
162.6, 162.9. Anal. Calcd for C21H20N2O4: C, 69.22; H, 5.33; N, 7.69.
Found: C, 69.31; H, 5.65; N, 7.63.
Benzyl 8(5-Benzyloxycarbonyl-3-butyl-4-methyl-2-pyrrolyl)-
3-methylindeno[2,1-b]pyrrole-2-carboxylate (26b). Chloroin-
denopyrrole 21a (1.24 g, 3.67 mmol) was reacted with pyrrole 22b (1.00
g, 3.69 mmol) under the foregoing conditions. Recrystallization from
acetoneꢀhexanes gave the dipyrrole (840 mg, 1.47 mmol, 40%) as an
off-white powder, mp 143.5ꢀ145 oC; 1H NMR (500 MHz, CDCl3)
δ0.89 (3H, t, J = 7.1 Hz), 1.29ꢀ1.42 (4H, m), 2.27 (3H, s), 2.37ꢀ2.44
(2H, m), 2.63 (3H, s), 4.94 (1H, s), 5.12ꢀ5.18 (2H, AB quartet, J = 12.6
Hz), 5.21 (1H, br d, J = 12.3 Hz), 5.28 (1H, br d, J = 12.3 Hz), 7.07 (1H,
dt, J = 1.0, 7.5 Hz), 7.15 (1H, d, J = 7.5 Hz), 7.27ꢀ7.41 (11H, m), 7.52
(1H, d, J = 7.5 Hz), 8.41 (1H, s, br), 9.20 (1H, br s); 13C NMR (CDCl3)
δ11.0, 11.9, 14.1, 23.0, 24.0, 34.0, 40.2, 65.8, 66.1, 118.3, 119.5, 123.0,
124.3, 124.6, 125.1, 127.5, 128.1, 128.20, 128.23, 128.37, 128.40, 128.7,
128.8, 129.6, 130.4, 136.4, 138.6, 146.4, 161.6. Anal. Calcd for
C37H36N2O4: C, 77.60; H, 6.33; N, 4.89. Found: C, 77.41; H, 6.18;
N, 5.03.
tert-Butyl 8(5-Benzyloxycarbonyl-3-ethyl-4-methyl-2-
pyrrolyl)-3-methylindeno[2,1-b]pyrrole-2-carboxylate (26d).
Indenopyrrole tert-butylester 17c (200 mg, 0.74 mmol) was dissolved in
carbon tetrachloride (18 mL), N-chlorosuccinimide (100 mg, 0.75
mmol) was added, and the solution was allowed to stir for 3 h. The
reaction mixture was then washed with water and 5% aqueous sodium
bicarbonate solution, dried over sodium sulfate, and rotary evaporated to
give the crude chloro-derivative 21b as a brown oil. The crude residue
was dissolved in glacial acetic acid (7 mL) along with R-free pyrrole
22a38c (160 mg, 0.666 mmol) and p-toluenesulfonic acid (10 mg) and
allowed to stir at room temperature for 2 h. The solution was diluted
with dichloromethane, washed with water and 5% aqueous sodium
bicarbonate solution, dried over sodium sulfate, and evaporated under
reduced pressure. The residue was purified on a silica column, eluting
with dichloromethane, and the product fractions were identified by
TLC, combined, and evaporated. The resulting brown oil crystallized
from ethanol to yield the indenodipyrrole 26d (81 mg, 0.159 mmol,
21%) as a pale green solid, mp 219ꢀ220 °C. IR (nujol) ν 3287 (NH
str.), 1665 cmꢀ1 (CdO str.); 1H NMR (500 MHz, CDCl3) δ 1.12 (3H,
t, J = 7.5 Hz), 1.58 (9H, s), 2.31 (3H, s), 2.51 (2H, q, J = 7.5 Hz), 2.59
(3H, s), 4.95 (1H, s), 5.21 (2H, s), 7.06 (1H, td, J = 0.8, 7.5 Hz), 7.15
(1H, d, J = 7.5 Hz), 7.27ꢀ7.38 (6H, m), 7.51 (1H, d, J = 7.5 Hz), 8.17
(1H, br s), 8.79 (1H, br s); 13C NMR (CDCl3) δ 10.9, 11.8, 16.3, 17.5,
28.7, 40.1, 65.8, 81.1, 118.3, 119.4, 120.9, 124.4, 124.8, 125.1, 125.6,
127.3, 128.1, 128.19, 128.24, 128.7, 129.5, 130.3, 136.6, 138.8, 142.3,
8(3-Ethyl-5-formyl-4-methyl-2-pyrrolyl)-3-methylindeno-
[2,1-b]pyrrole-2-carbaldehyde (27). Dipyrrole dicarboxylic acid
26a (1.00 g, 2.75 mmol) was dissolved in trifluoroacetic acid (15.5 mL)
and stirred for 2 min at room temperature. Trimethyl orthoformate
(3.1 mL) was added while maintaining the temperature at <25 °C, and
the resulting solution was heated to 40 °C and allowed to stir for an
additional 10 min. The mixture was then poured into iceꢀwater
(600 mL). Concentrated aqueous ammonia (15.5 mL) was added to
neutralize the acid, and the solution was allowed to stand overnight and
then suction filtered. Recrystallization from ethanolꢀwater gave the
dialdehyde (742 mg, 2.24 mmol, 81%) as a dark powder, mp 230 °C, dec
A small amount of product was chromatographed on a silica column
eluting with 30% ethyl acetate in toluene followed by recrystallization
from ethanol to give an analytical sample as brown crystals. IR (nujol) ν
1
3256, 3195 (NH str.), 1638, 1621 cmꢀ1 (CdO str.); H NMR (500
MHz, CDCl3) δ 1.04 (3H, t, J = 7.5 Hz), 2.28 (3H, s), 2.37ꢀ2.43 (2H, q,
J = 7.5 Hz), 2.60 (3H, s), 5.05 (1H, s), 7.11 (1H, td, J = 0.9, 7.5 Hz), 7.18
(1H, d, J = 7.5 Hz), 7.33 (1H, t, J = 7.5 Hz), 7.51 (1H, d, J = 7.5 Hz), 8.93
(1H, br s), 9.39 (1H, s), 9.53 (1H, s), 9.87 (1H, br s); 1H NMR (500
MHz, DMSO-d6) δ 0.39 (3H, br s), 1.62 (1H, br s), 1.68 (1H, br s), 2.13
(3H, s), 2.57 (3H, s), 5.16 (1H, s), 7.04ꢀ7.11 (2H, m), 7.28 (1H, td, J =
1.2, 7.3 Hz), 7.53 (1H, d, J = 7.5 Hz), 9.51 (1H, s), 9.58 (1H, s), 11.84
(1H, br s), 12.25 (1H, br s); 13C NMR (CDCl3) δ 8.9, 10.2, 15.8, 17.1,
40.2, 120.0, 125.3, 125.4, 126.2, 128.5, 129.1, 130.9, 131.7, 133.7, 134.2,
137.9, 145.7, 147.9, 176.8, 177.4; 13C NMR (DMSO-d6) δ 8.6 (br), 10.2
(br), 14.5, 16.1, 40.4, 119.3, 123.7 (br), 124.6, 125.0, 127.8, 128.3, 129.5
(br), 133.8, 134.4 (br), 137.5, 146.7, 148.1 (br), 177.0 (br), 177.9 (br);
HR MS (EI) calcd for C21H20N2O2: 332.1525, found 332.1524. Anal.
Calcd for C21H20N2O2: C, 75.88; H, 6.06; N, 8.43. Found: C, 75.83; H,
5.76; N, 8.39.
Indenoporphyrin 14a. A solution of p-toluenesulfonic acid (190
mg) in dichloromethane (70 mL) and methanol (14 mL) was prepared
in a 500 mL round-bottom flask. A solution of dialdehyde 27 (100 mg,
0.301 mmol) and dipyrrole dicarboxylic acid 2841 (101 mg, 0.316 mmol)
in dichloromethane (56 mL) and methanol (3.5 mL) was added
dropwise to the reaction flask over 2 h. The solution was allowed to
stir overnight in the dark, a saturated solution of zinc acetate in methanol
(4.5 mL) was added, and the reaction mixture was allowed to stir for
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The Journal of Organic Chemistry
ARTICLE
5 days open to the air for oxidation. The resulting solution was washed
with water and carefully back extracted with chloroform. The organic
solvent was then evaporated, and the residue was dissolved in trifluoro-
acetic acid (12 mL), diluted with chloroform, and washed with water and
5% aqueous sodium bicarbonate solution. The solvent was removed via
rotary evaporation, and the residue was purified on a short grade 3
neutral alumina column, eluting with dichloromethane. The first 600 mL
of colored eluant was evaporated and rechromatographed on grade 2
neutral alumina, eluting with toluene. The product fractions were
combined and rotary evaporated, and subsequent recrystallization from
chloroform and methanol gave the indenoporphyrin (40.6 mg, 0.077
mmol, 26%) as a dark green solid, mp >300 °C, dec; UVꢀvis (1%
Et3NꢀCHCl3) λmax (log ε) 352 (4.62), 418 (4.86), 445 (4.82), 467
(4.79), 622 (3.71), 672 nm (3.68); UVꢀvis (1% TFAꢀCHCl3) λmax
Nickel(II) Complex 30a. A solution of saturated nickel(II) acetate
in methanol (5 mL) was added to a solution of indenoporphyrin 14a
(10.5 mg, 0.020 mmol) in chloroform (10 mL), and the resulting
mixture was stirred under reflux overnight. The reaction mixture was
then diluted with chloroform (30 mL) and washed with water, and the
chloroform layer evaporated under reduced pressure. The residue was
chromatographed on grade 3 neutral alumina, eluting with dichloro-
methane. The product fractions were combined and recrystallized from
chloroformꢀmethanol to give the nickel complex in quantitative yield as
a dark green solid, mp 276ꢀ278 °C; UVꢀvis (CHCl3) λmax (log ε) 358
(4.18), 427 (4.72), 561 (3.58), 605 (3.56), 651 (3.45), 716 nm (3.16);
1H NMR (500 MHz, CDCl3) δ 1.63ꢀ1.67 (6H, 2 overlapping triplets,
J = 7.7 Hz), 1.68 (3H, t, J = 7.6 Hz), 3.18 (3H, s), 3.21 (6H, s), 3.23 (3H,
s), 3.63ꢀ3.69 (4H, 2 overlapping quartets, J = 7.7 Hz), 3.79 (2H, q, J =
7.6 Hz), 6.97ꢀ7.05 (2H, m), 7.41 (1H, dd, J = 1.4, 6.6 Hz), 7.82 (1H, d,
J = 7.2 Hz), 8.99 (1H, s), 9.11 (1H, s), 9.16 (1H, s); 13C NMR (CDCl3)
δ 11.2, 11.3, 11.8, 12.3, 16.9, 17.46, 17.51, 19.63, 19.67, 21.3, 97.3, 99.4,
101.6, 111.9, 122.9, 127.3, 127.7, 127.9, 132.1, 135.6, 139.7, 140.6, 140.8,
141.1, 141.6, 141.7, 141.8, 142.1, 144.1, 144.2, 144.4, 144.5, 145.2, 149.4,
152.4; HR MS (EI) calcd for C36H34N4Ni: 580.2137, found 580.2144.
Copper(II) Complex 30b. A solution of saturated copper(II)
acetate in methanol (5 mL) was added to a solution of indenoporphyrin
14a (11 mg, 0.021 mmol) in chloroform (10 mL), and the resulting
mixture was allowed to reflux for 2 h. The reaction mixture was then
diluted with chloroform (30 mL) and washed with water, and the
chloroform layer evaporated under reduced pressure. The residue was
purified on a grade 3 neutral alumina column, eluting with dichloro-
methane. The product fractions were combined and recrystallized from
chloroformꢀmethanol to give the copper complex (12.3 mg, 0.021
mmol, 100%) as a dark green solid, mp >300 °C; UVꢀvis (CHCl3) λmax
(log ε) 346 (4.34), 430 (4.78), 451 (4.83), 492 (3.85), 571 (3.70), 618
(3.65), 662 (3.55), 725 nm (3.33); HR MS (EI) calcd for C36H34N4Cu:
585.2079, found 585.2072.
1
(log ε) 434 (5.05), 485 (4.67), 613 nm (3.73); H NMR (500 MHz,
CDCl3) δ ꢀ1.22 (1H, br s), ꢀ0.05 (1H, br s), 1.70 (3H, t, J = 7.6 Hz),
1.72 (3H, t, J = 7.6 Hz), 1.76 (3H, t, J = 7.6 Hz), 3.21 (3H, s), 3.27
(3H, s), 3.34 (3H, s), 3.38 (3H, s), 3.71 (2H, q, J = 7.6 Hz), 3.80ꢀ3.90
(4H, m), 6.92 (1H, t, J = 7.1 Hz), 6.98 (1H, dt, J = 0.9, 7.4 Hz), 7.32
(1H, d, J = 7.1 Hz), 7.93 (1H, d, J = 7.4 Hz), 9.12 (1H, s), 9.29 (1H, s),
9.35 (1H, s); 1H NMR (500 MHz, TFAꢀCDCl3) δ ꢀ1.74 (1H, br s),
ꢀ0.97 (1H, br s), 1.61 (3H, t, J = 7.7 Hz), 1.66 (3H, t, J = 7.7 Hz), 1.76
(3H, t, J = 7.6 Hz), 3.36 (3H, s), 3.41 (3H, s), 3.42 (3H, s), 3.44 (3H, s),
3.87ꢀ3.98 (6H, m), 7.12 (1H, t, J = 7.3 Hz), 7.22 (1H, td, J = 0.8, 7.6
Hz), 7.57 (1H, d, J = 7.2 Hz), 8.04 (1H, d, J = 7.6 Hz), 9.84 (1H, s), 10.01
(1H, s), 10.04 (1H, s); 13C NMR (TFAꢀCDCl3) δ 11.60, 11.66, 12.3,
12.7, 15.6, 16.3, 16.4, 20.06, 20.07, 21.4, 100.81, 100.84, 101.4, 112.5, 125.5,
128.9, 130.2, 131.1, 133.5, 137.0, 137.3, 138.1, 139.8, 140.2, 140.6, 141.3,
141.9, 142.1, 143.7, 143.8, 144.9, 145.1, 147.6, 150.2, 152.3; HR MS (EI)
calcd for C36H36N4: 524.2940, found 524.2940. Anal. Calcd for C32H36N4:
C, 81.99; H, 7.08; N, 10.93. Found: C, 82.35; H, 6.92; N, 10.57.
Indenoporphyrin 14b. A solution of p-toluenesulfonic acid (160
mg) in dichloromethane (60 mL) and methanol (12 mL) was prepared
in a foil wrapped 500 mL round-bottom flask. A solution of indenodi-
pyrrole dicarboxylic acid 16b (100 mg, 0.255 mmol) and dipyrrole
dialdehyde 1526f (69 mg, 0.254 mmol) in dichloromethane (50 mL) and
methanol (5 mL) was added slowly to the reaction flask over a period of
2 h. The solution was allowed to stir overnight in the dark, then a
saturated solution of zinc acetate in methanol (4 mL) was added, and the
reaction mixture was allowed to stir for 3 days open to the air for
oxidation. The resulting solution was washed with water and carefully
back extracted with chloroform. The organic solvent was then evapo-
rated, and the residue was dissolved in trifluoroacetic acid (10 mL),
diluted with chloroform, and washed with water and 5% aqueous sodium
bicarbonate solution. The solvent was removed under reduced pressure,
and the residue was purified on a short grade 3 neutral alumina column,
eluting with dichloromethane. The colored eluants were combined,
evaporated, and rechromatographed on grade 3 neutral alumina, eluting
with toluene. The product fractions were combined and evaporated
under reduced pressure. Recrystallization from chloroformꢀmethanol
gave the indenoporphyrin (8.1 mg, 0.015 mmol, 6%) as a dark green
solid, mp >260 °C, dec; UVꢀvis (1% Et3NꢀCHCl3) λmax (log ε) 352
(4.61), 418 (4.85), 445 (4.81), 467 (4.77), 622 (3.78), 672 nm (3.78);
1H NMR (500 MHz, TFAꢀCDCl3) δ ꢀ2.37 (1H, s), 2.27 (1H, br s),
ꢀ1.52 (1H, s), ꢀ1.40 (1H, v br), 0.99 (3H, t, J = 7.9 Hz), 1.49 (2H,
sextet, J = 7.4 Hz), 1.62 (3H, t, J = 7.7 Hz), 1.67 (3H, t, J = 7.7 Hz),
2.05ꢀ2.11 (2H, m), 3.37 (3H, s), 3.44 (3H, s), 3.45 (3H, s), 3.46 (3H,
s), 3.90ꢀ3.95 (6H, m), 7.15 (1H, t, J = 7.4 Hz), 7.24 (1H, t, J = 7.8 Hz),
7.59 (1H, d, J = 7.1 Hz), 8.04 (1H, d, J = 7.5 Hz), 9.92 (1H, s), 10.08
(1H, s), 10.11 (1H, s); 13C NMR (TFAꢀCDCl3) δ 11.5, 11.6, 12.4,
12.6, 13.7, 16.2, 16.3, 20.1, 23.1, 28.1, 29.9, 33.2, 100.9, 101.0, 101.6,
113.1, 125.8, 129.2, 130.7, 131.3, 134.2, 137.1, 137.8, 138.8, 139.6, 140.6,
140.7, 141,2, 141.9, 142.1, 143.7, 145.7, 145.8, 147.2, 150.1, 152.2; HR
MS (EI) calcd for C38H40N4: 552.3253, found 552.3252.
Zinc Complex 30c. A solution of saturated zinc acetate in met-
hanol (5 mL) was added to a solution of indenoporphyrin 14a (10 mg,
0.019 mmol) in chloroform (10 mL), and the resulting mixture was
allowed to reflux for 1 h. The reaction mixture was then diluted with
chloroform (30 mL) and washed with water, and the chloroform layer
evaporated under reduced pressure. The residue was purified on a grade
3 neutral alumina column, eluting with dichloromethane. However, due
to low solubility, the crude product had to be loaded on to the column
with a few drops of pyrrolidine in dichloromethane due to its ability to
increase the solubility of zinc porphyrins in chlorinated solvents. The
product fractions were combined and recrystallized from chloroformꢀ
hexanes to give the zinc complex (8.2 mg, 0.014 mmol, 73%) as a very
dark blue solid, mp >300 °C; UVꢀvis (CHCl3) λmax (log ε) 347 (4.53),
389 (4.56), 436 (4.89), 459 (5.00), 498 (3.86), 580 (3.79), 624 (2.67),
674 (3.51), 737 nm (3.27); UVꢀvis (1% Pyrrolidine-CHCl3) λmax
(log ε) 348 (4.54), 385 (4.56), 446 (4.83), 470 (5.06), 505 (4.01), 594
1
(3.85), 641 (3.71), 768 nm (3.18); H NMR (500 MHz, CDCl3) δ
1.70ꢀ1.80 (9H, m), 3.31 (3H, s), 3.35 (3H, s), 3.37 (3H, s), 3.39
(3H, s), 3.79 (2H, q, J = 7.7 Hz), 3.82ꢀ3.89 (4H, m), 7.00 (1H, t, J = 7.2
Hz), 7.06 (1H, t, J = 7.5 Hz), 7.47 (1H, d, J = 7.2 Hz), 8.08 (1H, d, J = 7.5
1
Hz), 9.24 (1H, s), 9.36 (1H, s), 9.42 (1H, s); H NMR (500 MHz,
pyrrolidine-CDCl3) δ 1.68ꢀ1.74 (6H, m), 1.76 (3H, t, J = 7.6 Hz), 3.30
(3H, s), 3.34 (3H, s), 3.35 (3H, s), 3.36 (3H, s), 3.77 (2H, q, J = 7.7 Hz),
3.81 (2H, q, J = 7.6 Hz), 3.84 (2H, q, J = 7.5 Hz), 6.89 (1H, t, J = 7.3 Hz),
6.97 (1H, td, J = 1.0, 7.5 Hz), 7.39 (1H, dd, J = 0.8, 7.0 Hz), 8.03 (1H, d,
J = 7.5 Hz), 9.21 (1H, s), 9.31 (1H, s), 9.34 (1H, s); 13C NMR
(pyrrolidine-CDCl3) δ 11.3, 11.4, 11.9, 12.4, 16.9, 17.77, 17.78, 19.7,
19.8, 21.8, 97.3, 99.6, 101.6, 112.8, 122.8, 126.5, 127.0, 128.0, 131.7,
134.8, 135.0, 139.7, 140.1, 140.8, 141.9, 142.9, 143.5, 147.7, 148.7, 149.2,
150.2, 150.3, 152.0, 153.2, 160.4, 167.1; HR MS (EI) calcd for
C36H34N4Zn: 586.2075, found 586.2073.
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The Journal of Organic Chemistry
ARTICLE
’ ASSOCIATED CONTENT
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1
1
1
S
Supporting Information. Selected H NMR, Hꢀ H
b
COSY, HMQC, 13C NMR, MS, and UVꢀvis spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: tdlash@ilstu.edu.
Notes
†Porphyrins with Exocyclic Rings. Part 27. For Part 26 of this
series, see ref 13e.
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’ 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. B.E.S. also acknowledges a summer research
scholarship funded by M. E. Kurz. Funding for a 500 MHz NMR
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under grant no. CHE-0722385.
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