Synthesis and studies of thiacorroles

Article abstract of DOI:10.1021/jo100607t

The first examples of stable 22-thiacorroles containing a direct pyrrole-pyrrole bond were synthesized using thiophene monocarbinols as key precursors. Condensation of 1 equiv of thiophene monocarbinol with 1 equiv of substituted aldehyde and 1.5 equiv of pyrrole under refluxing propionic acid conditions followed by alumina column chromatographic purification yielded the desired 22-thiacorroles. Although the corrole formation had been observed with variety of substituted aldehydes, the stable thiacorroles were isolated in 2-3% yields only with 4- and 3-nitrobenzaldehydes. The stable thiacorroles were obtained only under harsh propionic acid conditions and any other mild reaction conditions did not yield 22-thiacorroles. The structure of thiacorroles were unambiguously established using mass, and 1D and 2D NMR spectroscopy. The NMR study indicated diminished ring current and distortion of 22-thiacorroles. DFT studies also supported the distortion of thiacorroles. The absorption spectra showed reduction in number of absorption bands and fluorescence study indicated that 22-thiacorroles are weakly fluorescent. The electrochemical studies indicated that 22-thiacorroles undergo easier reductions compared to thiaporphyrins.

Full text of DOI:10.1021/jo100607t

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Synthesis and Studies of Thiacorroles
Vijayendra S. Shetti,† Uday R. Prabhu,‡ and Mangalampalli Ravikanth*,†
†Department of Chemistry, Indian Institute of Technology, Bombay, Powai, Mumbai 400 076, India, and
‡NMR Research Centre, Indian Institute of Science, Bangalore 560012, India
ravikanth@chem.iitb.ac.in
Received March 30, 2010
The first examples of stable 22-thiacorroles containing a direct pyrrole-pyrrole bond were synthesized using
thiophene monocarbinols as key precursors. Condensation of 1 equiv of thiophene monocarbinol with
1 equiv of substituted aldehyde and 1.5 equiv of pyrrole under refluxing propionic acid conditions followed
by alumina column chromatographic purification yielded the desired 22-thiacorroles. Although the corrole
formation had been observed with variety of substituted aldehydes, the stable thiacorroles were isolated in
2-3% yields only with 4- and 3-nitrobenzaldehydes. The stable thiacorroles were obtained only under harsh
propionic acid conditions and any other mild reaction conditions did not yield 22-thiacorroles. The structure
of thiacorroles were unambiguously established using mass, and 1D and 2D NMR spectroscopy. The NMR
study indicated diminished ring current and distortion of 22-thiacorroles. DFT studies also supported the
distortion of thiacorroles. The absorption spectra showed reduction in number of absorption bands and
fluorescence study indicated that 22-thiacorroles are weakly fluorescent. The electrochemical studies
indicated that 22-thiacorroles undergo easier reductions compared to thiaporphyrins.
Introduction
broad and split. The corroles show an intense luminescence band
with a lifetime in the nanosecond region and exhibit a very small
Stokes shift.3 Corroles exhibit absorption and emission bands
that are hypsochromically shifted compared to porphyrins as a
result of reduction in π-conjugation. Corroles, like porphyrins,
form stable aromatic anions and mono- and dications.4 In
addition to above-mentioned differences, corroles and por-
phyrins also exhibit differences in their ability to form com-
plexes with a range of metal ions in unusual oxidation states.5
Corroles are aromatic tetrapyrrole macrocycles containing one
less carbon compared to porphyrins. Unlike porphyrins, corroles
have one direct pyrrole-pyrrole link, and the cavity size of
corrole is smaller than that of porphyrin.1 Corroles contain three
central pyrrole-type nitrogen atoms and one pyridine-type nitro-
gen atom, whereas porphyrins contain two of each type. Corroles
are stronger acids but weaker bases than porphyrins. Corroles
exhibit ill-defined and fewer Q-bands, whereas porphyrins exhibit
four clearly defined Q-bands.2 Because of the lower symmetry of
corroles compared to porphyrins, the Soret band in some cases is
(3) Flamigni, L.; Gryko, D. T. Chem. Soc. Rev. 2009, 38, 1635.
(4) (a) Kadish, K. M.; Caemelbecke, E. J. Solid State Electrochem. 2003, 7,
254. (b) Shen, J.; Shao, J.; Ou, Z.; Wenbo, E.; Koszarna, B.; Gryko, D. T.; Kadish,
K. M. Inorg. Chem. 2006, 45, 2251. (c) Ou, Z.; Shen, J.; Shao, J.; Wenbo, E.;
Galezowski, M.; Gryko, D. T.; Kadish, K. M. Inorg. Chem. 2007, 46, 2775.
(5) (a) Caemelbecke, E. V.; Will, S.; Autret, M.; Adamian, V. A.; Lex, J.;
Gisselbrecht, J.-P.; Gross, M.; Vogel, E.; Kadish, K. M. Inorg. Chem. 1996, 35,
184. (b) Meier-Callahan, A.; Gray, H. B.; Gross, Z. Inorg. Chem. 2000, 39, 3605. (c)
Bruckner, C.; Barta, C. A.; Brinas, R. P.; Krause Bauer, J. A. Inorg. Chem. 2003,
42, 1673. (d) Simkhovich, L.; Mahammed, A.; Goldberg, I.; Gross, Z. Chem.;
Eur. J. 2001, 7, 1041. (e) Kadish, K. M.; Erben, C.; Ou, Z.; Adamian, V. A.; Will,
S.; Vogel, E. Inorg. Chem. 2000, 39, 3312. (f) Kowalska, D.; Liu, X.; Tripathy, U.;
Mahammed, A.; Gross, Z.; Hirayama, S.; Steer, R. P. Inorg. Chem. 2009, 48, 2670.
(g) Stavitski, E.; Berg, A.; Ganguly, T.; Mahammed, A.; Gross, Z.; Levanon, H. J.
Am. Chem. Soc. 2004, 126, 6886. (h) Gross, Z.; Gray, H. B. Comments Inorg.
Chem. 2006, 27, 61. (i) Gross, Z. J. Biol. Inorg. Chem. 2001, 6, 733.
(1) (a) Gryko,D.T.Eur. J. Org. Chem. 2002, 1735. (b) Gross, Z.; Aviv, I. Chem.
Commun. 2007, 1987. (c) Aviv-Harel, I.; Gross, Z. Chem.;Eur. J. 2009, 15, 8382.
(2) (a) Sessler, J. L.; Weghorn, S. J. In Expanded, Contracted, & Isomeric
Porphyrins; Tetrahedron Organic Chemistry Series; Pergamon: Oxford, 1997; Vol. 15,
Chapter 2, p 11. (b) Paolesse, R. In The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 2, Chapter 11, p 201.
(c) Erben, C.; Will, S.; Kadish, K. M. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 2, Chapter 12,
p 233. (d) Mahammed, A.; Weaver, J. J.; Gray, H. B.; Abdelas, M.; Gross, Z.
Tetrahedron Lett. 2003, 44, 2077. (e) Ding, T.; Aleman, E. A.; Modarelli, D. A.;
Ziegler, C. J. J. Phys. Chem. A 2005, 109, 7411. (f) Ventura, B.; Espoosti, A. D.;
Koszarna, B.; Gryko, D. T.; Flamigni, L. New J. Chem. 2005, 29, 1559.
4172 J. Org. Chem. 2010, 75, 4172–4182
Published on Web 05/26/2010
DOI: 10.1021/jo100607t
r
2010 American Chemical Society

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After the discovery of easy synthetic routes for meso-sub-
stituted corroles by Gross et al.6 and Paolesse et al.7 in 1999,
the corrole macrocyles and their various metal derivatives
are now easily accessible to test their potential use in several
research fields including catalysis, materials science, and
medicine.8 The extensive research that has been carried out
in the past decade on corrole chemistry indicates that the
corrole macrocycle possesses very interesting properties that
can be tuned further by introduction of appropriate substit-
uents on the corrole framework. It is now very well established
from porphyrin chemistry that the properties of the macrocycle
can be altered not only by introducing substituents at the
periphery of the macrocycle but also by changing the inner
cores.9 The replacement of one or two nitrogens of porphyrins
with other heteroatoms such as C, S, O, Se, and Te resulted in
heteroatom-substituted porphyrins or core-modified porphyr-
ins that possess very interesting physicochemical properties. The
heteroporphyrins are shown to stabilize metals in unusual oxi-
dation states10 and can act as good energy acceptors in por-
phyrin based donor-acceptor systems.11 Similar to porphyrins,
it is possible to modify the corrole core by replacing one or two
inner nitrogen atoms with other heteroatoms, which would lead
to new type of core-modified corroles.1a The possible core-
modified corroles containing one or two heteroatoms such as
oxygen and sulfur that are derived from their corresponding
heteroporphyrins are shown in Scheme 1. The following two
different types of monoheterocorroles can be obtained from
monoheteroporphyrins: (1) the monoheterocorrole that has
direct pyrrole-pyrrole link III and (2) the monoheterocorrole
that has pyrrole-heterocycle (furan/thiophene) link IV. The
symmetrical diheteroatom-substituted porphyrins can give only
one type of corrole, which has direct pyrrole-heterocycle link V.
The unsymmetrical diheteroatom-substituted porphyrins can
also give two different types of corroles containing direct
pyrrole-heterocycle link VI and VII (Scheme 1). Among all
of the above-discussed possible heterocrroles, only mono-oxo
corroles containing both types of direct links III and IV and
SCHEME 1. Various Possible Mono- and Diheteroatom-Sub-
stituted Corroles
(6) Gross, Z.; Galili, N.; Saltsman, I. Angew. Chem., Int. Ed. 1999, 38,
1427.
(7) Paolesse, R.; Jaquinod, L.; Nurco, D. J.; Mini, S.; Sagone, F.; Boschi,
T.; Smith, K M. Chem. Commun. 1999, 1307.
dioxacorrole of type V have been synthesized successfully so far
by using different approaches.12
(8) (a) Gross, Z.; Simkhovich, L.; Galili, N. Chem. Commun. 1999, 599.
(b) Zhang, R.; Harischandra, D. N.; Newcomb, M. Chem.;Eur. J. 2005, 11,
5713. (c) Luobeznova, I.; Raizman, M.; Goldberg, I.; Gross, Z. Inorg. Chem.
2006, 45, 386. (d) Wang, S. H.; Mandimutsira, B. S.; Todd, R.; Ramdhanie,
B.; Fox, J. P.; Goldberg, D. P. J. Am. Chem. Soc. 2004, 126, 18. (e)
Mahammed, A.; Gray, H. B.; Meier-Callahan, A. E.; Gross, Z. J. Am. Chem.
Soc. 2003, 125, 1162. (f) Grodkowski, J.; Neta, P.; Fujita, E.; Mahammed,
A.; Simkhovichand, L.; Gross, Z. J. Phys. Chem. A 2002, 106, 4772. (g)
Barbe, J.-M.; Canard, G.; Brandes, S.; Jerome, F.; Dubois., G.; Guilard, R.
Dalton Trans. 2004, 1208. (h) Mahammed, A.; Weaver, J. J.; Gray, H. B.;
Abdelas, M.; Gross, Z. Tetrahedron Lett. 2003, 44, 2077. (i) Li, C.-Y.; Zhang,
X.-B.; Han, Z.-X.; Akermark, B.; Sun, L.; Shen, G.-L.; Yu, R.-Q. Analyst
2006, 133, 388. (j) Aviezer, D.; Cotton, S.; David, M.; Segev, A.; Khaselev,
N.; Galili, N.; Gross, Z.; Yayon, A. Cancer Res. 2000, 60, 2973. (k)
Mahammed, A.; Gray, H. B.; Weaver, J. J.; Sorasaenee, K.; Gross, Z.
Bioconjugate Chem. 2004, 15, 738. (l) Agadjanian, H.; Weaver, J. J.; Ma-
hammed, A.; Rentsenorj, A.; Bass, S.; Kim, J.; Dmochowski, I. J.; Margalit,
R.; Gray, H. B.; Gross, Z.; Medina-Kauwe, L. K. Pharm. Res. 2006, 23, 367.
(9) (a) Wojaczynski, J.; Latos-Grazynski, L. Coord. Chem. Rev. 2000,
204, 113. (b) Gupta, I.; Ravikanth, M. Coord. Chem. Rev. 2006, 250, 468.
(10) Latos-Grazynski, L. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 2,
p 361.
Chandrashekar and co-workers first synthesized 5,10,15-
triaryl-22-oxacorrole 1, which was obtained as a byproduct in
8% yield during their attempts to synthesize the oxasmarag-
dyrin12a,13 by [3 þ 2] acid-catalyzed condensation of 16-oxa-
tripyrrane 2 and meso-aryldipyrromethane 3. Lee and co-wor-
kers12b synthesized the same type of 22-oxacorrole 1by the [2 þ 2]
approach as shown in Scheme 2. According to the [2 þ 2]
approach, the acid-catalyzed condensation of furylpyrro-
methane alcohol 4 with meso-aryldipyrromethane 3 gave cor-
role 1in 15% yield (Scheme 2). Lee and co-workers14 also used a
regioisomer of furylpyrromethane alcohol 5, which on con-
densation with meso-aryldipyrromethane 3 in the presence of
(12) (a) Narayanan, S. J.; Sridevi, B.; Chandrashekar, T. K. Org. Lett.
1999, 1, 587. (b) Cho, W.-S.; Lee, C.-H. Tetrahedron Lett. 2000, 41, 697. (c)
Pawlicki, M.; Latos-Grazynski, L.; Szterenberg, L. J. Org. Chem. 2002, 67,
5644.
(13) Sankar, J.; Anand, V. G.; Venkatraman, S.; Rath, H.; Chandrashe-
kar, T. K. Org. Lett. 2002, 4, 4233.
(11) (a) Shetti, V. S.; Ravikanth, M. Eur. J. Org. Chem. 2010, 494. (b)
Yedukondalu, M.; Maity, D. K.; Ravikanth, M. Eur. J. Org. Chem. 2010,
1544. (c) Punidha, S.; Sinha, J.; Kumar, A.; Ravikanth, M. J. Org. Chem.
2008, 73, 323. (d) Gupta, I.; Ravikanth, M. Inorg. Chim. Acta 2007, 360,
1731. (e) Rai, S.; Ravikanth, M. Tetrahedron 2007, 63, 2455.
(14) Lee, C.-H.; Cho, W.-S.; Ka, J.-W.; Kim, H.-J.; Lee, P. H. Bull.
Korean Chem. Soc. 2000, 21, 429.
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SCHEME 2. (a) [3 þ 2] and (b) [2 þ 2] Approaches for Synthesis
SCHEME 4. Three Different Synthetic Approaches for Mono-
meso Free 22-Oxacorrole 7 Containing a Direct Pyrrole-Pyrrole
Bond
of 22-Oxacorrole 1 Containing a Direct Pyrrole-Pyrrole Bond
In this paper, we describe our attempts to synthesize the first
examples of stable thiacorroles using a thiophene monocarbinol
approach. We successfully synthesized 22-thiacorroles by con-
densing thiophene monocarbinol with aryl aldehyde and pyr-
role in Adler’s refluxing propionic acid conditions16 and studied
their spectral and electrochemical properties.
SCHEME 3. [2 þ 2] Approach for Synthesis of Monooxacorrole
6 Containing a Direct Furan-Pyrrole Bond
Results and Discussion
Synthesis of Thiacorroles. Our attempts to prepare the
thiacorroles started in 2004 by using 2-(arylhydroxymethyl)-
thiophene 11 (thiophene monocarbinol) as the key precur-
sor.17 We condensed 1 equiv of 11 with 1 equiv of arylaldehyde
and 1.5 equiv of pyrrole in propionic acid at refluxing tempera-
ture to prepare the thiacorrole 12 (Scheme 6). However, we were
not successful in obtaining even a trace amount of the thiacor-
role 12, but the condensation surprisingly yielded 21-thiapor-
phyrin 13 (Scheme 6). We adopted this methodology and
prepared a series of monofunctionalized 21-thia- and 21-oxa-
porphyrins using functionalized thiophene/furan monocarbinols.
The monofunctionalized 21-heteroporphyrins were used further
to prepare several covalently linked porphyrin dyads containing
two different porphyrin subunits.11 The failure to obtain the
required 21-thiacorrole 12 was not clearly understood, but the
formation of 21-thiaporphyrin 13 could be inferred as the result
of electrophilic attack of aldehyde at the 5-position of thiophene
in one of the reaction steps. We then attempted to prepare 21,23-
dithiacorrole 14 by condensing 1 equiv of the thiophene mono-
carbinol 2-[(p-tolyl)hydroxymethyl]thiophene 11 with 16-thiat-
ripyrrin18 15 in propionic acid under refluxing conditions for 3 h
acid followed by oxidation with DDQ gave the second type
of corrole, 21-oxacorrole 6 in 9% yield (Scheme 3).
Chandrashekar and co-workers recently used three differ-
ent approaches15 to synthesize mono-meso free 22-corrole 7,
which has a direct pyrrole-pyrrole link as shown in Scheme 4.
Latos-Grazynski and co-workers12c reported the synthesis
of 21,23-dioxacorrole 8 containing a direct pyrrole-furan
link by acid-catalyzed condensation of 2,5-bis(arylhydroxy-
methyl)furan 9, 2-(phenylhydroxymethyl)furan 10, and pyr-
role (Scheme 5).
Thus, a perusal of literature reveals that only oxacorroles are
known, and to the best of our knowledge, there is no report on
thiacorroles. This may be due to the presence of a large sulfur
atom that destabilizes the formation of contracted thiacorroles.
(16) Adler, A. D.; Longo, F. R.; Finarelli, J. D.; Goldmacher, J.; Assour,
J.; Korsakoff, L. J. Org. Chem. 1967, 32, 476.
(17) (a) Gupta, I.; Ravikanth, M. J. Org. Chem. 2004, 69, 6796. (b) Gupta,
I.; Agarwal, N.; Ravikanth, M. Eur. J. Org. Chem. 2004, 1693.
(18) Heo, P. Y.; Lee, C. H. Bull. Korean Chem. Soc. 1996, 17, 515.
(15) Sankar, J.; Rath, H.; PrabhuRaja, V.; Chandrashekar, T. K.; Vittal,
J. J. J. Org. Chem. 2004, 69, 5135.
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SCHEME 5. Synthetic Approach for Preparation of 21,23-Dioxacorrole 8 Containing a Direct Furan-Pyrrole Bond
SCHEME 6. Initial Synthetic Approach for Thiacorroles That Led to the Formation of Monothiaporphyrins
(Scheme 7). TLC analysis showed a green spot correspond-
ing to the expected compound 14 along with several other
spots including the spot corresponding to the formation of
21,23-dithiaporphyrin 16. The crude compound was sub-
jected to rigorous column chromatographic purification
and, the trace amount of 21,23-dithiacorrole 14 was isolated.
ES-MS analysis showed the molecular ion peak confirming
the formation of 21,23-dithiacorrole 14 (Figures S1 and S2,
Supporting Information). The absorption spectra of 21,23-
dithiacorroles showed one broad Q-band at ∼680 nm with a
shoulder and one broad Soret band at ∼400 nm. However,
the NMR spectra was very complicated since the compound
14 was unstable in solution and decomposed in very short
period of time. Any alterations in the reaction conditions and
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SCHEME 7. Unsuccessful Approach for the Synthesis of
Dithiacorrole 14
We then directed our attention to prepare monothiacorroles,
which we expected to be more stable than their dithia analogues.
We condensed 1 equiv of 11a with 1.5 equiv of pyrrole and 1
equiv of various substituted aldehydes such as 4-tolualdehyde,
4-anisaldehyde, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde,
4-cyanobenzaldehyde, pentafluobenzaldehyde, and 4-pyridine
carboxaldehyde in propionic acid at refluxing temperature for
3 h (Scheme 8). TLC analysis showed a green spot of the desired
monothiacorrole (Figures S4 and S5, Supporting Information)
along with 21-thiaporphyrin in some of these reactions. How-
ever, we did not observe even a trace amount of corrole forma-
tion when we used 4-pyridinecarboxaldehyde, which resulted in
exclusive formation of 21-thiaporphyrin. No formation of
corrole or porphyrin was observed when we used pentafluoro-
benzaldehyde under these reaction conditions. In most of the
cases, we noticed a trace amount of corrole along with a major
amount of the corresponding 21-thiaporphyrin. However, the
thiacorroles that were isolated after hectic chromatographic
purifications decomposed rapidly. Surprisingly, when we used
1 equiv of 4-nitrobenzaldehyde condensed with 1 equiv of 11a
and 1.5 equiv of pyrrole under the same refluxing propionic
acid conditions, TLC analysis indicated the formation of only
corrole as a green spot and no formation of 21-thiaporphyrin
was noticed. Similar observation was made by Paolesse and co-
workers during the synthesis of normal corroles with 4-/3-
nitrobenzaldehydes.19 Thus, this condensation resulted in the
formation of one of the following thiacorroles: the thiacorrole
having a direct R-Rpyrrole-pyrrole bond, 17, orthethiacorrole
having a direct R-R thiophene-pyrrole bond, 18. The crude
compound was subjected to alumina column chromatographic
purification using peteroleum ether/dichloromethane, and one
of the possible thiacorroles 17 or 18 was isolated as a dark green
powder in 3% yield. ES-MS showed a molecular ion peak
confirming the formation of the thiacorrole 17 or 18. When we
changed the reaction conditions from Adler’s to Lindsey’s reac-
tion conditions,20 the 21-thiacorrole formation was not observed.
change of thiophene monocarbinols did not stabilize the
21,23-dithiacorroles, and the dithiacorroles decomposed in-
stantaneously. The equilibrium structure calculated for
21,23-dithiacorrole 14 at the B3LYP/6-31G(d) level of the-
ory indicated the highly distorted nature of dithiacorrole
(Figure S3, Supporting Information). Thus, it was evident
that 21,23-dithiacorrole 14 containing two inner core sulfur
atoms was very unstable and decomposed immediately, un-
like 21,23-dioxacorroles that were isolated and characterized
by Grazynski and co-workers.12c
SCHEME 8. Synthesis of 22-Monothiacorrole Using a Thiophene Monocarbinol Approach
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FIGURE 1. Comparison of the selected region of the 1H NMR spectra of (a) 17 and (b) 19 recorded in CDCl3.
Thus, the formation of thiacorrole 17 or 18 required harsh reac-
tion conditions but simple column chromatograpic purification
to isolate pure desired thiacorrole 17 or 18. The thiacorrole is
freely soluble in common organic solvents such as dichloro-
methane, chloroform, and toluene and stable in solid form for
over 6 months on the benchtop.
SCHEME 9. Synthesis of β-Substituted Derivatives of 22-
Thiacorroles 19 and 22
To deduce the structure of thiacorrole formed, we carried out
extensive 1D and 2D NMR studies that supported the forma-
tion of thiacorrole 17 and not thiacorrole 18 as discussed below.
1
The H NMR spectrum of thiacorrole 17 recorded in CDCl3
showed eight distinct doublets in the 8.0-9.0 ppm region
corresponding to two β-thiophene protons and six β-pyrrole
protons of pyrrole rings A, B, and C (Figure 1a). This indicates
that the eight protons corresponding to one thiophene and three
pyrrole rings of thiacorrole are chemically inequivalent. We first
attempted to assign the two β-thiophene protons of thiacorrole
17. We synthesized the β-thiophene-substituted thiacorrole 19
to identify the two β-thiophene protons of thiacorrole 17
(Scheme 9). To synthesize the thiacorrole 19, we required the
thiophene monocarbinol 21, which was synthesized by treating
3,4-dimethoxythiophene with 1.2 equiv of n-BuLi followed by
p-tolualdehyde in THF. Column chromatography on silica
yielded pure thiophene monocarbinol 21 as a pale yellow oily
compound in 55% yield. The thiacorrole 19 was synthesized by
condensing 1 equiv of 21 with 1 equiv of 4-nitrobenzaldehyde
and 1.5 equiv of pyrrole in propionic acid at refluxing tempera-
ture for 3 h followed by alumina column chromatographic
purification afforded 19 in 2% yield. Thiacorrole 19 was
confirmed by molecular ion peak in the mass spectrum. The
shown in Figure 1b. It is clear from the NMR spectrum of 19
that the six β-pyrrole protons appeared as six doublets and were
slightly upfield shifted compared to 17 as a result of the presence
of two methoxy groups at thiophene carbons. A careful obser-
vation of the 1H NMR spectra of corroles 17 and 19 indicates
that the two doublets at 8.06 (H2) and 8.50 (H1) ppm of 17 were
absent in thiacorrole 19 (Figure 1). This suggest that the two
doublets at 8.06 and 8.50 ppm in thiacorrole 17 are due to
1
aromatic region of the H NMR spectrum recorded for 19 is
(19) Paolesse, R.; Nardis, S.; Sagone, F.; Khoury, R. G. J. Org. Chem.
2001, 66, 550.
(20) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827.
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FIGURE 2. Partial 1H-1H COSY spectrum of 17 recorded in CDCl3.
β-thiophene protons (Figure 2), and NOESY spectra of 17 fur-
ther (Figure S22, Supporting Information) confirmed the as-
signment of β-thiophene protons. Furthermore, in a HSQC
experiment, the doublets at 8.06 and 8.50 ppm showed correla-
tion with the thiophene carbons at 127.4 and 127.6 ppm, res-
pectively (Figure S23, Supporting Information). To assign the
six pyrrole protons of rings A, B, and C, we looked at the
inner NH signals in the 1H NMR spectrum of thiacorrole 17.
We expected two signals for two inner NH protons. However,
only one singlet corresponding to one inner NH proton at
-1.29 ppm was observed at room temperature. Thus it can be
inferred as, at room temperature, one inner NH can be detected
on the NMR time scale and the other NH may be involved in
rapid tautomersim. The chemical shift position of the inner NH
signal in thiacorrole 17 is significantly downfield shifted com-
pared to 21-monothiaporphyrin, supporting the diminished
ring current effect of monothiacorrole. In the 1H-1H COSY
spectrum, the signal at -1.29 ppm showed crosspeaks with the
two doublets at 8.40 and 8.91 ppm (Figure S18, Supporting
Information). This indicates that the two doublets at 8.40 and
8.91 ppm are due to β-protons of the pyrrole ring that contains
the localized NH. We carried out variable-tempearture NMR
studies to probe in detail about the inner NH signals. However,
we observed only one inner NH signal that was slightly up-
field shifted when the temparature was decreased to -40 °C
(Figure 3a). Interestingly, the two doublets at 8.40 and 8.91
ppm were also slightly downfield shifted and appeared as
quartets due to 4J coupling of β-pyrrole protons with an inner
NH proton (Figure 3b). The fact that only one inner NH signal
appeared at -1.29 ppm even at -40 °C suggests that the other
inner NH proton that is undergoing rapid tautomersim may be
present on the bipyrrole unit. This analysis indicated that the
two doublets at 8.40 and 8.91 ppm are due to H3 and H4 of
pyrrole ring A, respectively. The HSQC study showed that two
doublets at 8.40 and 8.91 ppm were connected to the carbons at
126.1 and 128.1 ppm, respectively. We assigned the doublet at
8.91 ppm to H4 proton because of its proximity to the meso-
nitrophenyl group and the signal at 8.40 ppm to H3 due to its
proximity to the meso-tolyl group. This analysis was further
1
supported by H-1H COSY and NOESY studies. The con-
nectivities observed in HMBC studies also showed that H3 and
H4 were flanked by these two meso-substituents (Figure S24a,
Supporting Information).
To arrest the tautomerism of the inner NH proton of the
bipyrrole unit, we carried out protonation studies on thia-
corrole 17 by treatment with trifluoroacetic acid. On pro-
tonation, the tautomerism was arrested, and as expected, we
observed three signals at -1.40, -1.57, and -1.65 ppm at
-40 °C (Figure S19a and S19b, Supporting Information).13
The bipyrrole protons H5, H6, H7, and H8 were assigned on
the basis of a series of TOCSY and NOE (1D and 2D) experi-
ments carried out on thiacorroles 17 and 19. We initially carried
out a conventional 2D NOESY experiment on thiacorrole 17 in
which the doublet at 8.91 ppm showed a cross peak with one of
the doublets in the cluster of signals in the 8.2-8.3 ppm region.
The band selective homonuclear decoupled NOESY (BASHD-
NOESY)21 experiment was performed to understand precisely
the spatial interaction of the protons resonating at 8.91 ppm to
the signal in the cluster. We found that the signal at 8.91 ppm is
(21) (a) Bruschweiler,R.;Griesinger,C.;Sorensen,O.W.;Ernst,R.R.J. Magn.
Reson. 1988, 78, 178. (b) Krishnamurthy, V. V. Magn. Reson. Chem. 1997, 35, 9.
4178 J. Org. Chem. Vol. 75, No. 12, 2010

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FIGURE 3. Variable-temparature 1H NMR studies of 17 in CDCl3: (a) inner NH signal, and (b) β-pyrrole H4 signal.
spatially coupled with the meso m-tolyl protons (Figure 4). This
observation inferred the spatial proximity of the pyrrole ring
containing localized NH (ring A) to the meso-tolyl group.
Apart from this, no other decisive information was obtained
from 2D NOESY experiment.
other two remainining doublets at 8.54 ppm and a doublet
at 8.26 ppm in the cluster of the 8.20-8.30 ppm region were
assigned to H5 and H6 of pyrrole ring B of 17, respectively.
We extended the same synthetic methodology to prepare
two more examples of thiacorroles 20 and 22, but the
formation of 22 was observed in trace amount. These two
corroles were characterized by HRMS and NMR studies.
We also carried out quantum-chemical calculations by
applying Density Functional Theory. Equilibrium struc-
tures, calculated at the B3LYP/6-31G(d) level of theory
revealed that the thiacorrole structure 17 is considerably
distorted (Figure S33, Supporting Information) but rela-
tively more stable than the thiacorrole structure 18 (Figure
S34, Supporting Information) .
Absorption, Emission and Electrochemical Properties of
Thiacorroles. The absorption properties of thiacorroles 17,
19, 20, and 22 were studied in dichloromethane, and the data
is presented in Table 1. The absorption spectra of thiacorrole 17
and its protonated form 17Hþ are shown in Figure 5. Since the
corroles are tetrapyrrolic macrocycles closely related to porphy-
rins, the absorption properties of corroles are expected to be
similar with porphyrins. Generally, the studies on azacorroles
showed that they exhibit similar absorption features as porphy-
rins with one strong Soret band at 410-430 nm and three to four
Q-bands in the 500-700 nm region.3 The reported 21-oxacor-
roles also exhibited one strong Soret band and weak Q-bands in
the visible region with the features identical with corresponding
Next we turned our attention toward the thiacorrole 19,
which contains two distinctly separated singlets for meth-
oxy groups at 3.33 and 4.44 ppm for NOE studies. When the
singlet at 4.44 ppm was selectively excited in a 1D NOE
experiment, the NOE enhancement was observed for doub-
let at 8.61 ppm (Figure S26b, Supporting Information). As
described before for 17, the cross peak analysis of the inner
1
NH signal in the H-1H COSY spectrum of 19 revealed
that the signal at 8.61 ppm was not from the pyrrole unit
that contains the localized NH. This indicated that the
methoxy group is spatially nearer to one of the β-pyrrole
protons of the bipyrrolic unit. The 1H-1H COSY spectrum
indicated that the doublet at 8.61 ppm is correlated with the
doublet at 8.34 ppm. Since the two doublets at 8.34 and
8.61 ppm of thiacorrole 19 are corresponding to the doub-
lets at 8.43 and 8.65 ppm, respectively, of thiacorrole 17
(Figure 1), the doublets at 8.43 and 8.65 ppm were assigned
to H7 and H8 of pyrrole ring C of 17, respectively. Further-
more, the HMBC experiment indicates that the thiophene
proton H1 and the protons of pyrrole ring C, H7 and H8,
show a connectivity to a carbon at 140.2 ppm supporting
that pyrrole ring C is adjacent to the thiophene ring. The
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FIGURE 4. (A) 500 MHz NMR spectrum of thiacorrole 17 in CDCl3. The two solid lines show correlation of the overlapped multiplet of two
protons to the single NOESY cross-peak. (B) Band selctive homonuclear decoupled (BASHD)-NOESY experiment unambiguously correlated
singlet corresponding to a proton to the NOESY cross-peak is denoted by a solid line.
TABLE 1. Absorption and Fluorescence Data for Monothiacorroles
singlet state lifetime τ ns (% component)
compound
absorption bands λ nm (log ε)
fluorescence quantum yield (φf)
1
2
3
17
19
20
22
439 (4.72)
442 (4.79)
431 (4.80)
433 (4.85)
623 (4.39)
626 (4.60)
616 (4.48)
620 (4.68)
0.0050
0.0020
0.0046
0.0019
0.95 (2%)
0.89 (4%)
1.39 (3%)
0.81 (4%)
7.84 (2%)
7.68 (1%)
7.45 (7%)
6.0 (1%)
0.093 (96%)
0.087 (95%)
0.120 (90%)
0.100 (95%)
21-oxaporphyrins.22 Interestingly, the 22-thiacorroles exhi-
bited one broad strong Soret-like band at ∼435 nm and one
broad Q-band-like transition at ∼620 nm indicating that the
thiacorroles are less symmetric in nature unlike the reported
oxacorroles. On protonation, the compounds showed split
Soret-like bands and experienced bathochromic shifts in
both Soret- and Q-band-like absorption bands.
The fluorescence properties of thiacorroles were studied
using steady-state and time-resolved fluorescence techni-
ques. The thiacorroles exhibited one broad ill-defined fluor-
escence band centered at ∼660 nm with low quantum yields
(Table 1). Thus, unlike reported oxacorroles,22 the thiacor-
roles are very weakly fluorescent, which is because of the pre-
sence of sulfur atom. The singlet state life times of thiacor-
roles were measured using time correlated single photon
counting technique.23 The thiacorroles were excited at 406
nm and emissions were detected on the emission peak posi-
tions of thiacorroles. The fluorescence decays of thiacorroles
were fitted to three exponentials, and the lifetimes are
presented in Table 1. These corroles exhibited one major
long component decay with ∼100 ps (95%) and two short
components with 1 ns (2%) and 7 ns (3%). These observa-
tions are in agreement with the azacorroles.2e
FIGURE 5. Absorption spectra of 17 (thick line) and 17Hþ (dashed
line) recorded in dichloromethane.
The electrochemical properties of 22-thiacorroles were
investigated using cyclic voltammetry (CV) and differential
pulse voltammetry (DPV) in dichloromethane with tetrabu-
tylammonium perchlorate as supporting electrolyte. A re-
presentative reduction wave of thiacorrole 17 is shown in
Figure 6, and the data is presented in Table 2 along with
monothiaporphyrin and the parent meso-aryl corrole. In
general, the thiacorroles exhibited one to two irreversible
oxidations and three to four quasi or irreversible reductions.
(22) Sridevi, B.; Narayanan, S. J.; Chandrashekar, T. K.; Englich, U.;
Ruhlandt-Senge, K. Chem.;Eur. J. 2000, 6, 2554.
(23) Kumaresan, D.; Datta, A.; Ravikanth, M. Chem. Phys. Lett. 2004,
395, 87.
4180 J. Org. Chem. Vol. 75, No. 12, 2010

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JOCArticle
(d, J = 7.9 Hz, 2H, Ar), 7.34 (d, J = 7.9 Hz, 2H, Ar) ppm; 13
C
NMR (100 MHz, CDCl3) δ 21.2, 21.3, 57.2, 57.2, 60.8, 69.4,
69.5, 95.0, 95.1, 126.3, 129.2, 137.6, 139.8, 150.6 ppm; HRMS
(ESþ) m/z calcd for C14H16O3SNa (M þ Na)þ 287.0718, found
287.0707.
General Synthesis of 22-Monothiacorroles. One equivalent of
thiophene/β-substituted thiophene monocarbinol, 1 equiv of 3-/
4-nitrobenzaldehyde, and 1.5 equiv of freshly distilled pyrrole
were refluxed in propionic acid for 3 h. The propionic acid was
removed completely by vacuum distillation, and the resulting
black residue was washed several times with water and oven-
dried. Further, it was dissolved in dichloromethane and sub-
jected to flash column chromatography on basic alumina. The
required monothiacorrole was eluted as dark green fraction in
petroleum ether/dichloromethane (60:40) and was recrystallized
from dichloromethane/n-hexane solvent mixture to get pure
monothiacorrole as dark solid.
FIGURE 6. Reduction waves of cyclic voltammogram (thick line)
and differential pulse voltammogram (dashed line) of thiacorrole 17
recorded in dichloromethane containing 0.1 M TBAP at scan rate of
50 mV s-1
.
TABLE 2. Electrochemical Data (in V) for Monothiacorroles
5-(p-Tolyl)-10,15-bis(p-nitrophenyl)-22-thiacorrole (17). Yield
3%, mp >300 °C. 1H NMR (400 MHz, CDCl3) δ -1.29 (s, 1H,
NH), 2.65 (s, 3H, CH3), 7.64 (d, J = 8.2 Hz, 2H, Ar), 8.06 (d,
J = 4.3 Hz, 1H, β-thiophene), 8.23-8.31 (m, 7H, 6Ar þ β-
pyrrole), 8.40 (d, J = 4.9 Hz, 1H, β-pyrrole), 8.43 (d, J = 4.2 Hz,
1H, β-pyrrole), 8.50 (d, J = 4.3 Hz, 1H, β-thiophene), 8.54 (d,
J = 4.6 Hz, 1H, β-pyrrole), 8.55-8.62 (m, 4H, Ar), 8.65 (d, J = 4.2
potential V vs SCE
compound oxidation
reduction
Δ redox (V)
17
19
0.75 0.98 -0.82 -1.08 -1.40 -1.68
0.71 0.94 -0.95 -1.06 -1.40 -1.67
1.57
1.66
1.84
1.77
2.10
2.04
20
22
0.74 0.98
-1.10
-1.75
0.93 -0.84 -1.12 -1.33 -1.74
-1.06
Hz, 1H, β-pyrrole), 8.91 (d, J = 4.9 Hz, 1H, β-pyrrole) ppm; 13
C
STPPHa
1.04
4-NTPCb 0.95 1.39
-1.09
-1.64
NMR (100 MHz, CDCl3) δ 21.5, 110.0, 113.8, 118.3, 122.2, 122.8,
123.9, 125.7, 126.1, 127.4, 127.6, 128.1, 129.7, 131.3, 132.8, 135.0,
135.1, 136.4, 137.1, 137.3, 138.6, 138.7, 140.2, 146.5, 147.4, 148.1,
149.4, 150.3, 153.3, 154.6 ppm; HRMS (ESþ) m/z calcd for
C38H26N5O4S (M þ H)þ 648.1706, found 648.1707.
a5,10,15,20-Tetraphenyl-21-thiaporphyrin. b5,10,15-Tris(4-nitrophe-
nyl)corrole.
The thiacorroles were found to undergo easy reductions
compared to the thiaporphyrins, indicating the electron-
deficient nature of thiacorroles.
β-2,3-(Dimethoxy)-meso-5-(p-tolyl)-10,15- bis(p-nitrophenyl)-
22-thiacorrole (19). Yield 2%, mp >300 °C. 1H NMR (400
MHz, CDCl3) δ -0.97 (s, 1H, NH), 2.64 (s, 3H, CH3), 3.33 (s,
3H, OCH3), 4.44 (s, 3H, OCH3), 7.60 (d, J = 7.6 Hz, 2H, Ar),
8.17-8.22 (m, 5H, Ar), 8.28 (d, J = 8.0 Hz, 2H, Ar), 8.30 (d,
J = 5.1 Hz, 1H, β-pyrrole), 8.34 (d, J = 4.0 Hz, 1H, β-pyr-
role), 8.45 (d, J = 4.7 Hz, 1H, β-pyrrole), 8.54-8.60 (m, 4H,
Ar þ β-pyrrole), 8.61 (d, J = 4.0 Hz, 1H, β-pyrrole), 8.78
(d, J = 5.1 Hz, 1H, β-pyrrole) ppm; 13C NMR (100 MHz,
CDCl3) δ 21.4, 61.0, 62.5, 109.7, 115.0, 119.0, 120.3, 122.2,
122.7, 124.9, 126.3, 128.0, 128.8, 129.1, 130.9, 132.7, 134.4,
134.9, 135.0, 135.2, 136.7, 137.9, 138.04, 139.0, 139.1, 146.4,
146.6, 147.2, 147.4, 148.0, 149.2, 150.1, 154.9 ppm; HRMS
(ESþ) m/z calcd for C40H30N5O6S (M þ H)þ 708.1917, found
708.1932.
Conclusions
In conclusion, we synthesized the first examples of four
stable 22-thiacorroles by condensing thiophene monocarbinol
with 4-/3-nitrobenzaldehyde and pyrrole in propionic acid
at refluxing temperature. The formation of 22-thiacorroles
requires harsh reaction conditions. The 21-thiaporphyrin was
the major stable product when we used any other substituted
aldehyde instead of 4-/3-nitrobenzaldehyde under same reac-
tion conditions. 1D and 2D NMR, DFT, and absorption
studies supported the distorted nature of 22-thiacorroles.
The thiacorroles are easier to reduce and are weakly fluores-
cent. Thus, our study concluded that the thiacorroles can be
isolated in stable form with nitrobenzaldehydes and possess
different properties compared to thiaporphyrins.
5-(p-Tolyl)-10,15-bis(m-nitrophenyl)-22-thiacorrole (20). Yield
2%, mp >300 °C. 1H NMR (400 MHz, CDCl3) δ -1.30 (s, 1H,
NH), 2.64(s,3H, CH3),7.63(d, J= 7.9 Hz, 2H, Ar), 7.86-7.93(m,
2H, Ar), 8.04 (d, J = 4.2 Hz, 1H, β-thiophene), 8.23 (d, J = 4.5 Hz,
1H, β-pyrrole), 8.25 (d, J = 7.9 Hz, 2H, Ar), 8.38 (d, J = 4.8 Hz,
1H, β-pyrrole), 8.39-8.42 (m, 3H, 2 Ar þ 1 β-pyrrole), 8.50 (d, J=
4.5 Hz, 1H, β-pyrrole), 8.51 (d, J=4.5Hz,1H,β-thiophene), 8.54 -
8.59 (m, 3H, Ar), 8.65 (d, J = 4.2 Hz, 1H, β-pyrrole), 8.91 (d, J=
4.8 Hz, 1H, β-pyrrole), 8.94 - 8.99 (m, 1H, Ar) ppm; 13C NMR
(100 MHz, CDCl3) δ 21.5, 109.5, 113.8, 118.2, 122.6, 122.7, 123.7,
125.8, 126.2, 127.3, 127.7, 128.2, 128.5, 128.6, 129.8, 131.3, 132.8,
135.1, 136.8, 137.2, 137.7, 138.5, 138.9, 140.0, 140.5, 141.7, 144.2,
147.4, 147.9, 150.5, 153.5, 155.1 ppm; HRMS (ESþ) m/z calcd for
C38H26N5O4S (M þ H)þ 648.1706, found 648.1711.
Experimental Section
Synthesis of 2-[r-(p-Tolyl)-r-hydroxymethyl]-3,4-(dimethoxy)-
thiophene (21). N,N,N0,N0-Tetramethylethylenediamine (1.25 mL,
8.3 mmol) and n-BuLi (5.2 mL of 1.6 M solution in hexane,
8.3 mmol) were added to a solution of 3,4-dimethoxy thiophene
(1 g, 6.9 mmol) in diethyl ether (30 mL) and stirred at 0 °C for
1 h. An ice-cold solution of p-tolualdehyde (0.98 mL, 8.33 mmol)
was added, and stirring was continued for an additional 1 h.
Saturated aqueous NH4Cl solution was added to the reaction
mixture and was extracted with diethyl ether (3 ꢀ 50 mL). The
organic layers were combined, washed with saturated brine, and
dried over sodium sulfate. The crude product was concentrated
in vacuo and purified by silica gel column chromatography
using petroleum ether/ethyl acetate (95:5) to afford the diol as
pale yellow oil (1 g, yield 55%). 1H NMR (400 MHz, CDCl3) δ
2.33 (s, 3H, CH3), 2.65 (s, 1H, bs, OH), 3.78 (s, 3H, OCH3), 3.79
(s, 3H, OCH3), 6.07 (s, 1H, CH), 6.09 (s, 1H, R-thiophene), 7.15
β-2,3-(Dimethoxy)-meso-5-(p-tolyl)-10,15-bis(m-nitrophenyl)-
22-thiacorrole (22). Mp >300 °C. 1H NMR (400 MHz, CDCl3)
δ -1.00 (s, 1H, NH), 2.64 (s, 3H, CH3), 3.32 (s, 3H, OCH3), 4.44
(s, 3H, OCH3), 7.61 (d, J = 7.6 Hz, 2H, Ar), 7.86 - 7.93 (m, 2H,
Ar), 8.15 (d, J = 4.5 Hz, 1H, β-pyrrole), 8.20 (d, J = 7.9 Hz, 2H,
Ar), 8.27 (d, J = 4.8 Hz, 1H, β-pyrrole), 8.33 (d, J = 4.5 Hz, 1H,
β-pyrrole), 8.37 - 8.39 (m, 2H, Ar), 8.44 (d, J = 4.5 Hz, 1H, β-
pyrrole), 8.55 - 8.57 (m, 2H, Ar), 8.62 (d, J = 4.2 Hz, 1H, β-
pyrrole), 8.80(d,J= 5.4 Hz, 1H, β-pyrrole), 8.92-8.99 (m, 2H, Ar)
J. Org. Chem. Vol. 75, No. 12, 2010 4181

Shetti et al.
JOCArticle
ppm; HRMS (ESþ) m/z calcd for C40H30N5O6S (M þ H)þ
also thank Mr. M. Yedukondalu and Ms. Jasmine Sinha for
their help during various stages of this investigation.
708.1917, found 708.1920.
Acknowledgment. M.R. thanks DST for financial support.
V.S.S. and U.R.P. thank CSIR for the fellowship. The authors
are grateful to Prof. N. Suryaprakash, NMR Research centre,
IISc, Bangalore for providing NMR facility and to Dr. Dilip K.
Maity, BARC Mumbai for computational facility. The authors
Supporting Information Available: Copies of high-resolu-
tion ES-MS data, 1D and 2D NMR spectra of selected com-
pounds, and computational details on thiacorroles 14, 17, and 18.
This material is available free of charge via the Internet at http://
pubs.acs.org.
4182 J. Org. Chem. Vol. 75, No. 12, 2010