Two-step synthesis of stable dioxadicarbaporphyrins from bis(3-indenyl)METHANE

Article abstract of DOI:10.1002/anie.201206385

Porphyrin without N: Bilin analogues and related aromatic dicarbaporphyrinoids have been prepared from bis(3-indenyl)methane. Even though all four pyrrole rings from the porphyrin macrocycle have been replaced by two furan and two indene subunits, the sys

Full text of DOI:10.1002/anie.201206385

Angewandte
Chemie
DOI: 10.1002/anie.201206385
Dicarbaporphyrinoids
Two-Step Synthesis of Stable Dioxadicarbaporphyrins from
Bis(3-indenyl)methane**
Timothy D. Lash,* Aaron D. Lammer, and Gregory M. Ferrence
The origin of the aromatic characteristics of porphyrins (1a)
and related systems remains the topic of considerable
debate.[1–3] Although porphyrins and related macrocycles are
often considered to be examples of bridged annulenes,[4–6]
some theoretical studies have concluded that the aromatic
properties of porphyrinoids are primarily due to the individ-
ual pyrrolic rings.[3,7] However, the extent to which the
pyrrolic nitrogens contribute to the aromatic properties of
porphyrins has been brought into question.[1,2] In particular,
dideazaporphyrins 2, which lack these pyrrole-type nitrogens,
have been shown to be strongly diatropic and to possess
porphyrin-like electronic absorption spectra.[1,8] In previous
studies, we have probed the aromatic properties of porphyr-
inoids by replacing one or more of the pyrrolic subunits with
carbocyclic rings.[5,6] Monocarbaporphyrins related to 1b have
been investigated in detail,[9] but far less is known about
dicarbaporphyrinoid systems.[10–16] In principle, these inves-
tigations could be extended to quatyrin (1c), the theoretically
important hydrocarbon analogue of the porphyrins,[5]
although severe crowding within the macrocyclic cavity may
make this system inaccessible.[17] Syntheses of opp-dicarba-
porphyrinoids 3[10] and 4[11] with two carbocyclic rings
interspersed by pyrrolic moieties have been reported, but
these porphyrin analogues proved to be rather unstable.[10–12]
Nevertheless, dicarbaporphyrin 3 exhibited strongly diatropic
characteristics and the UV/Vis spectrum for this species
closely resembled the spectra for true porphyrins.[10,13,14] More
recently, examples of adj-dicarbaporphyrinoid systems have
been reported[15,16] including carbaazuliporphyrin 5.[15] These
porphyrinoids proved to be far more stable than 3 and 4 and
exhibited significant macrocyclic aromaticity. Unfortunately,
to date no examples of adj-dicarbaporphyrins 6 with two
adjacent cyclopentadiene rings have been synthesized. In our
investigations into mono- and dicarbaporphyrins, indene units
have usually been used in place of cyclopentadiene moieties
because of synthetic considerations.[5,6] For this reason, we set
out to target dibenzo-macrocycles related to porphyrinoid 6.
It is well known that indene reacts with aldehydes under
basic conditions to afford fulvenes (Scheme 1).[15] We antici-
pated that bis(3-indenyl)methane 7[18] could similarly be used
Scheme 1. Synthesis of fulvenes from indene.
to prepare fulvene derivatives and that this chemistry might
be utilized in the synthesis of adj-dicarbaporphyrinoids.
Owing to the low reactivity of pyrrole aldehydes, this
hypothesis was investigated using furan aldehydes. Bis-
(3-indenyl)methane was reacted with difurylmethane dialde-
hyde 8 under basic conditions in an attempt to generate the
heterodicarbaporphyrinoid 9 (Scheme 2), but no indication of
macrocyclic products could be discerned. This result may be
due to an unfavorable geometry of the intermediates for
macrocyclic ring closure. Therefore, the formation of fulvene
products was examined by reacting 7 with 2 equivalents of
a series of aromatic aldehydes and KOH in refluxing
methanol. When furfural was reacted 7 under these con-
ditions, a fulvene product was generated as a red precipitate.
[*] Prof. Dr. T. D. Lash, A. D. Lammer, Prof. Dr. G. M. Ferrence
Department of Chemistry, Illinois State University
Normal, IL 61790-4160 (USA)
E-mail: tdlash@ilstu.edu
[**] Part 62 in the series “Conjugated Macrocycles Related to the
Porphyrins”. This work was supported by the National Science
Foundation (NSF) (CHE-0911699 and CHE-1212691) and the
Petroleum Research Fund, administered by the American Chemical
Society. The authors also thank the Youngstown State University
Structure & Chemical Instrumentation Facility’s Matthias Zeller for
X-ray data collection. The diffractometer was funded by the NSF
(0087210), the Ohio Board of Regents (CAP-491), and YSU.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206385.
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Scheme 2. Proposed syntheses of fulvenes and a porphyrin analogue
from bis(3-indenyl)methane.
In small scale reactions using 50 mg of 7, this product was
formed in up to 98% yield, although the yields were lower
(73–78%) in larger scale reactions using > 1 g of bis-
(3-indenyl)methane. Similar results were obtained using
thiophene-2-carbaldehyde, benzaldehyde, or 4-substituted
benzaldehydes. Initially, it had been anticipated that diful-
venes 10 would be formed in these reactions, but the 1H NMR
spectra for these products showed that they lacked the
expected plane of symmetry. A possible explanation for these
results was that the E,Z isomer 11 had been produced rather
than the E,E isomer 10. The 1H NMR spectrum for the
furfural derivative showed the presence of a broad 2H triplet
(J = 2 Hz) at 4.11 ppm that was coupled to two 1H resonances
Scheme 3. Synthesis of bilin analogues.
=
=
at 6.96 and 7.24 ppm. This indicated that a CH C-CH2-C CH
unit was present within the structure. While this is consistent
with structure 11, detailed analyses using H–1H COSY, nOe
1
difference 1H NMR, 13C NMR, and HSQC indicated that the
fully conjugated species 12a was in actual fact the product of
this chemistry (Scheme 3). The thiophene product could
similarly be attributed to 12b, whereas the benzaldehyde-
derived series were consistent with structures 13a–d. These
unusual conjugated species are structurally related to fully
conjugated open-chain tetrapyrroles (bilins) and can there-
fore be considered to be bilin analogues. The structure of the
dithiophene bilin analogue 12b was confirmed by X-ray
crystallography, which clearly demonstrated the asymmetry
of the two indenyl moieties (Figure 1). There are two
crystallographically independent molecules in the asymmetric
unit of the structure. The indene containing the apical
methylene was identified in both independent molecules.
Identification on the basis of difference Fourier location of
the hydrogen atoms matched identification of the methylene
carbon atoms on the basis of carbon–carbon bond distances.
Bilins 12 and 13 gave orange solutions in dichloro-
methane, and the UV/Vis spectra showed several broad
absorptions between 280 and 450 nm. However, when tri-
fluoroacetic acid (TFA) was added a new species was
generated. Addition of TFA to 12a gave a dark green
solution that showed strong absorptions at 450, 623, and
819 nm. The 1H NMR spectrum for 12a in TFA/CDCl3
showed that the system had gained a plane of symmetry and
a 4H singlet was observed at 4.63 ppm. These results indicated
Figure 1. X-ray crystal structure of dithiophene bilin analogue 12b.
Selected bond lengths [ꢀ]: C4–C21 1.388(8), C1–C21 1.457(8), C6–C22
1.466(8), C9–C22 1.487(8). Selected non-bonded separations [ꢀ]:
C4···C6 2.487(8), C1···C19 2.501(8), C9···C11 2.492(9), C14···C16
4.57(1), S(23)···S(24) 3.650(3). One of two crystallographically inde-
pendent molecules is shown for clarity.
that protonation had primarily occurred on an indene unit
and that a resonance-delocalized cation, represented by the
canonical form 12aH+, had been generated (Scheme 3).
Similar results were obtained for the dithiophene system
12b. Furthermore, all of the benzaldehyde-derived bilin
analogues 13a–d gave rise to the equivalent protonated
species 13H+. These unusual cations are resonance-delocal-
ized carbenium ions that are formed under very mild
conditions. The protonated species derived from 13a and
13b showed a broad absorption in their UV/Vis spectra at 727
and 729 nm, respectively, but this band was bathochromically
shifted to 769 nm for the tert-butyl substituted version 13 f.
The dimethoxy bilin analogue gave the largest red shift for
this series, showing a long wavelength band at 811 nm and its
spectra more closely resembled that of 12a and 12b. The
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cation derived from 12a was somewhat unstable and, after an
hour or so, the 1H NMR spectrum of 12a in TFA/CDCl3
showed only broad unresolved absorptions. However, pro-
tonated bilins 12bH+ and 13H+ were all reasonably stable and
persisted in solution for prolonged periods of time.
The facile protonation and unique properties of bilin
analogues 12 and 13 demonstrate that these systems are
important in their own right. However, our primary goal was
to prepare macrocyclic products from these intermediates.
These studies focused on the reactivity of the furfural-derived
bilin 12a, as furans are far more reactive towards electrophilic
substitution than thiophenes. When 12a was reacted with
paraformaldehyde in the presence of an acid catalyst, low
yields of porphyrinoid product 9 were noted (Scheme 4). The
best results were obtained when 12a was reacted with one
the best results were obtained when using 10 mL of CH2Cl2.
Refluxing the reaction in 1,2-dichloroethane gave poor
results, but reactions in refluxing CH2Cl2 raised the yield to
39% for the phenyl substituted macrocycle. The substrates 4-
chloro- and 4-bromobenzaldehyde (15b and 15c) also gave
the best results under these conditions, affording the corre-
sponding aryl substituted porphyrinoids 14b and 14c in 26%
and 40% yields, respectively. At room temperature, 14b and
14c were obtained in only slightly lower yields (23% and
38%, respectively) and these results indicated that electron-
withdrawing groups may have a beneficial effect on these
reactions. However, 4-nitrobenzaldehyde gave only 12%
yield of 14d under optimized conditions. In this case, the
best results were obtained under more dilute conditions
(100 mL of CH2Cl2 for 100 mg of 12a) and at room temper-
ature. Reasonable yields of 14e and 14 f could also be
obtained under dilute conditions (15% and 10%, respec-
tively) using dialdehydes 15e and 15 f. Although linked
diporphyrinoids might be formed from dialdehydes 15e and
15 f, this type of product has not as yet been isolated from
these reactions. Nevertheless, the ease of introducing diverse
functional groups could potentially allow these dicarbapor-
phyrinoids to be incorporated into supramolecular systems.
Macrocycles 9 and 14a–f afforded orange solutions that
gave porphyrin-like UV/Vis spectra, each with a Soret band
between 436 and 440 nm (Figure 2). For 9, the Soret band
Scheme 4. Synthesis of dioxadicarbaporphyrins.
equivalent of (CH2O)n in refluxing 20% TFA/1,2-dichloro-
ethane, followed by oxidation with aqueous ferric chloride.
When the oxidation step was not carried out, the conjugated
macrocycle could still be isolated, but the product was
contaminated with by-products that gave rise to broad
1
Figure 2. UV/Vis spectra of 14a in CH2Cl2 (c) and 2% TFA-CH2Cl2
(cation 14aH+; a).
absorptions in the H NMR spectra. The oxidation appeared
to decompose these impurities as well as facilitating the
formation of 9. Even so, the best yields for this reaction were
only 5%, and oxidation with 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ) led to complete decomposition. Much
better results were obtained when using aromatic aldehydes.
The reaction of 12a with one equivalent of benzaldehyde
in the presence of 0.5 equivalents of BF3·Et2O in CH2Cl2 at
room temperature, followed by a brief treatment with DDQ,
gave 15-phenyldioxadicarbaporphyrin 14a in up to 10% yield
(Scheme 4). When one equivalent of BF3·Et2O was used,
much lower yields were obtained, but lower concentrations of
the catalyst also gave poor results. The quantity of solvent
used was also a factor, and for reactions with 100 mg of 12a
appeared at 436 nm and Q-type bands appeared at 510 and
547 nm. Moreover, weak absorptions were observed at 668
and 689 nm. Phenyl substituted porphyrinoid 14a exhibited
minor bathochromic shifts, showing these absorptions at 439,
513, 549, 673, and 690 nm (Figure 2). The addition of TFA to
solutions of 9 or 14 in CH2Cl2 gave the green-colored
protonated species 9H+ and 14H+, respectively, which gave
complex UV/Vis spectra showing multiple bands in the Soret
region and four absorptions between 600 and 810 nm
1
(Figure 2). The H NMR spectra for dioxadicarbaporphyrins
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9 and 14 showed that the macrocycles are highly diatropic.
Impure samples of 9 in CDCl3 gave resonances for the meso-
protons downfield at 10.06 (1H), 9.58 (2H), and 9.31 ppm
(1H), and the internal CH groups afforded a 2H singlet at
À3.60 ppm. However, pure 9 was poorly soluble in organic
remarkably planar, as evidenced by the 0.0619 ꢀ root-mean-
square distance the framework atoms lie from the plane
defined by the 24 framework atoms. The largest deviations
from the plane are C5 (0.086(7) ꢀ), C15 (À0.094(9) ꢀ), C17
(0.11(1) ꢀ), and C18 (0.090(8) ꢀ), but these deviate by less
than 0.06 ꢀ from the aforementioned plane. The structure
exhibits framework bond distances consistent with a nearly
idealized delocalized p-bonding model with the p-systems for
the indenyl benzo-units decoupled from the [18]annulene
core, as evidenced by the more single-bond-like C1–C2
(1.476(2) ꢀ), and C3–C4 (1.478(2) ꢀ) bond distances. As
would be expected, the phenyl group is canted 77.10(4)8
relative to the mean macrocyclic plane.
In conclusion, a unique series of bilin analogues has been
prepared in excellent yields by reacting aromatic aldehydes
with bis(3-indenyl)methane in the presence of potassium
hydroxide in refluxing methanol. The furfural-derived bilin
analogue condensed with aromatic aldehydes in the presence
of BF3·Et2O to give aryl substituted dioxadicarbaporphyrins
in good yields (10–40%). An unsubstituted dibenzodioxadi-
carbaporphyrin was also obtained by reacting the bilin
analogue with paraformaldehyde. The new series of porphy-
rin analogues are stable compounds and are the first examples
of porphyrinoids that incorporate two adjacent indene units.
The ease of formation of these conjugated macrocycles will no
doubt facilitate detailed investigations into this new class of
aromatic bridged annulenes.
1
solvents and the H NMR spectrum showed the equivalent
resonances at 9.91, 9.40, 9.15, and À4.29 ppm, and these shifts
are attributed to aggregation effects. The 1H NMR spectra for
aryl substituted porphyrinoids 14 also showed strong dia-
tropic ring currents, and the meso-protons for 14a were
observed at 10.05 (1H) and 9.58 ppm (2H), whereas the
internal CH groups gave a 2H resonance at À3.61 ppm
(Figure 3). The NMR spectra for the cations 9H+ and 14H+
in TFA/CDCl3 demonstrated that the protonated species
Figure 3. 500 MHz 1H NMR spectrum of phenyl substituted dioxadi-
carbaporphyrin 14a. Proton assignment numbering follows the con-
vention used for compound 9 in Scheme 4.
Received: August 8, 2012
Published online: && &&, &&&&
retained a powerful diamagnetic ring current. For 14H+, the
interior CH2 group gave a singlet at À4.74 ppm, whereas the
indene CH group appeared at À2.96 ppm. The meso-protons
were significantly shifted downfield to give singlets at 10.54
(1H) and 10.62 ppm (2H). 13C NMR spectra for 9 and 14 in
CDCl3 confirmed that the macrocycles have a plane of
symmetry, but this is lost for the protonated species 9H+ and
14H+.
The X-ray crystal structure of 14a has also been obtained
(Figure 4). The solid state structure has the molecule centered
on a crystallographic two-fold axis of rotation which contains
H5, C5, C15, C15a, C15d, and H15d. The macrocycle is
Keywords: aromaticity · bridged annulenes · carbaporphyrins ·
.
fulvenes · indenes
[1] T. D. Lash, S. A. Jones, G. M. Ferrence, J. Am. Chem. Soc. 2010,
132, 12786 – 12787.
[2] T. D. Lash, J. Porphyrins Phthalocyanines 2011, 15, 1093 – 1115.
[3] Y. Nakagami, R. Sekine, J.-i. Aihara, Org. Biomol. Chem. 2012,
10, 5219 – 5229.
[4] E. Vogel, J. Heterocycl. Chem. 1996, 33, 1461 – 1487.
[5] T. D. Lash, Synlett 2000, 279 – 295.
[6] T. D. Lash, Eur. J. Org. Chem. 2007, 5461 – 5481.
[7] J.-i. Aihara, M. Makino, Org. Biomol. Chem. 2010, 8,
261 – 266.
[8] See also: E. Pacholska-Dudziak, L. Szterenberg, L.
Latos-Grazynski, Chem. Eur. J. 2011, 17, 3500 – 3511.
[9] a) T. D. Lash, M. J. Hayes, Angew. Chem. 1997, 109,
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Chem. 2002, 67, 4860 – 4874; c) D. Liu, T. D. Lash, J.
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[10] T. D. Lash, J. L. Romanic, M. J. Hayes, J. D. Spence,
Chem. Commun. 1999, 819 – 820.
[11] S. R. Graham, D. A. Colby, T. D. Lash, Angew. Chem.
2002, 114, 1429 – 1432; Angew. Chem. Int. Ed. 2002,
Figure 4. X-ray crystal structure of dicarbaporphyrinoid 14a. Selected bond lengths
[ꢀ]: C1–C2 1.476(2), C3–C4 1.478(2), C4–C5 1.398(2), C4–C21 1.404(2), C21–C1
1.392(2), C15–C16 1.398(2), C16–C17 1.406(2), C17–C18 1.373(2), C18–C19
1.398(2), C19–C20 1.388(2), C20–C1 1.396(2), C16–O24 1.383(2), O24–C19
1.390(2). The molecule is centered on a crystallographic two-fold axis of rotation
which contains H5, C5, C15, C15a, C15d, and H15d.
41, 1371 – 1374.
[12] For examples of resorcinol-derived dicarbaporphyri-
noids, see: L. Xu, T. D. Lash, Tetrahedron Lett. 2006,
47, 8863 – 8866.
[13] Related doubly-N-confused porphyrins are also
known; see: a) H. Furuta, H. Maeda, A. Osuka, J.
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Am. Chem. Soc. 2000, 122, 803 – 807; b) H. Maeda, A. Osuka, H.
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104.
[14] Heterodicarbaporphyrinoids with alternating azulene and furan
or thiophene rings have also been reported: a) N. Sprutta, M.
Swiderska, L. Latos-Grazynski, J. Am. Chem. Soc. 2005, 127,
13108 – 13109; b) N. Sprutta, M. Siczek, L. Latos-Grazynski, M.
Pawlicki, L. Szterenberg, T. Lis, J. Org. Chem. 2007, 72, 9501 –
9509.
[17] Conjugated macrocycles with the same carbon skeleton as
quatyrin have been prepared from calix[4]azulenes; see: a) T. D.
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8833; b) N. Sprutta, S. Mackowiak, M. Kocik, L. Szterenberg, T.
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[18] H. Li, C. L. Stern, T. J. Marks, Macromolecules 2005, 38, 9015 –
9027.
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Communications
Dicarbaporphyrinoids
T. D. Lash,* A. D. Lammer,
G. M. Ferrence
&&&& — &&&&
Two-Step Synthesis of Stable
Dioxadicarbaporphyrins from Bis(3-
indenyl)methane
Porphyrin without N: Bilin analogues and
related aromatic dicarbaporphyrinoids
have been prepared from bis(3-indenyl)-
methane. Even though all four pyrrole
rings from the porphyrin macrocycle have
been replaced by two furan and two
indene subunits, the system retains por-
phyrin-like UV/Vis spectra and highly
diatropic characteristics.
6
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