4,4,9,9-Tetraphenyl pyrroloindolizine: A structural analogue of calix[2]pyrrole

Article abstract of DOI:10.1039/c2ob25228g

Synthesis, spectral and structural characterization of a pyrroloindolizine derivative having structural similarity with calix[2]pyrrole is described. Here, two pyrrole rings are connected with two meso-carbon atoms having an N,α-linkage and an α,β-linkage

Full text of DOI:10.1039/c2ob25228g

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Organic &
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2012, 10, 3600
www.rsc.org/obc
COMMUNICATION
4,4,9,9-Tetraphenyl pyrroloindolizine: a structural analogue of calix[2]
pyrrole†
K. C. Gowri Sreedevi,a Ajesh P. Thomas,b S. Ramakrishnan,a P. S. Salini,a M. G. Derry Holaday,a
M. L. P. Reddyc and A. Srinivasan*b
Received 31st January 2012, Accepted 13th March 2012
DOI: 10.1039/c2ob25228g
supramolecular self assemblies in spite of the increased ring
strain.9
Synthesis, spectral and structural characterization of a pyr-
roloindolizine derivative having structural similarity with
calix[2]pyrrole is described. Here, two pyrrole rings are con-
nected with two meso-carbon atoms having an N,α-linkage
and an α,β-linkage to afford the smallest analogue in the
calixpyrrole family. Detailed NMR spectroscopic studies
along with single crystal X-ray analysis confirm the assigned
structure of the molecule.
In addition to regular porphyrinoids, mutations such as con-
fusion and fusion are found to have a place in porphyrins since
the discovery of N-confused porphyrins.10 Recently, Furuta et al.
reported a corrole isomer, “norrole” 4 with an N,β-link as a by-
product from the oxidative ring closure of N-confused bilane and
called a neo-confused derivative.11 Subsequently, Lash et al. pre-
sented the first examples of neo-confused porphyrins 5 where a
pyrrole nitrogen is connected to a meso-carbon (Fig. 1).12
On the other hand, calix[4]pyrrole, first prepared by Baeyer in
1886,13 is a class of fully meso-substituted porphyrinogen-like
macrocycles. As in the case of porphyrins, normal, expanded
and confused structural variations of calixpyrroles are well
known in the literature, which are widely used as receptors for
various anions both in solution and in the solid state.14 However,
the corresponding contracted calixpyrroles are not known in the
literature, probably due to the higher order ring strain in those
derivatives. In 1958, Treibs and Kolm15 reported a meso-free
cyclic molecule 6, by an acid catalyzed cyclo-condensation
of ethyl 2-methyl-3-pyrrolecarboxylate with formaldehyde,
where the two pyrrole rings are connected with the meso-
carbon atoms through α,β-linkages (Fig. 1) and which fall into
the category of pyrroloindolizine derivatives having valuable
biological activities.16 Herein, we report the synthesis, spectral
and structural characterization of a 4,4,9,9-tetraphenyl pyrroloin-
dolizine derivative, which is a structural analogue of calix[2]
pyrrole (7b) with N,α- and α,β-linkages to the meso-
carbon atoms.
Porphyrinoids, with their structural variations such as, normal,
contracted, and expanded derivatives, are explored for appli-
cations in molecular recognition, catalysis, material science and
medicine.1 In particular, the contracted porphyrinoids have con-
tinued to gather much interest since the first synthesis of sub-
phthalocyanines 1,2 the lower homologues of phthalocyanines
formed by three instead of four N-fused 1,3-diiminoisoindole
units, by Meller and Ossko in 1972,2a which represent fascinat-
ing examples of non-planar aromaticity with unique spectral and
electronic features. Later, in 2005, Torres et al. reported subpor-
phyrazines 2,3 by the removal of the three fused benzene rings
from the subphthalocyanine. In sharp contrast, the first subpor-
phyrin, tribenzosubporphine 3, with a similar electronic structure
to subphthalocyanines 1, was prepared by the group of Osuka in
2006 as the B(III) complex under harsh reaction conditions
(Fig. 1).4 Subsequently, series of boron free subporphyrinoids,
such as subpyriporphyrin,5 [14]benzotriphyrin(2.1.1)6 and
β-substituted, meso-free[14]triphyrin(2.1.1)7 have been reported.
Very recently, our group reported a β-unsubstituted, meso-aryl
[14]triphyrin (2.1.1) in its free-base form.8 These set of com-
pounds are found to be ideal candidates for the construction of
The title compound is synthesized by acid-catalyzed conden-
sation reaction, where 2-(diphenylhydroxymethyl) pyrrole 817 in
dichloromethane is allowed to stir for 2 h in the presence of
BF3·OEt2 as an acid catalyst (Scheme 1). The solvent is removed
and the dark residue is then purified by column chromatography
on silica gel using hexane as the eluent, to afford a white solid
7b in 20% yield. The compound is soluble in common organic
solvents. The identity of 7b was confirmed by various spectro-
scopic methods, and finally by single crystal X-ray analysis,
revealing the exact structure of the molecule.
aPhotosciences and Photonics Section, National Institute for
Interdisciplinary Science and Technology (NIIST-CSIR), Trivandrum-
695019, Kerala, India
bNational Institute of Science Education and Research (NISER),
Bhubaneswar-751005, Odisha, India. E-mail: srini@niser.ac.in
cInorganic Chemistry Section, Chemical Sciences and Technology
Division, National Institute for Interdisciplinary Science and Technology
(NIIST-CSIR), Trivandrum-695019, Kerala, India
†Electronic supplementary information (ESI) available: Synthetic pro-
cedure and spectral data for 7b. CCDC 855537 for 7b. For ESI and crys-
tallographic data in CIF or other electronic format see DOI: 10.1039/
c2ob25228g
The FAB mass spectrum showed a peak at m/z 464.29 point-
ing out the formation of the smallest self-condensed product
between two units of 8 (m/z = 249) by the elimination of two
3600 | Org. Biomol. Chem., 2012, 10, 3600–3605
This journal is © The Royal Society of Chemistry 2012

View Article Online
Fig. 1 Porphyrinoids
water molecules. The expected structure of the compound is
either 7a, as seen by the group of Treibs and Kolm, or 7b.
The 1H NMR spectrum of the compound (7) in CDCl3 at
room temperature is shown in Fig. 2, which shows only one NH,
twenty phenyl protons and five pyrrolic CH leading towards the
asymmetric nature of the molecule, thus ruling out the possibility
of 7a. The NH proton resonates as a singlet at 7.60 ppm (a) and
is confirmed by D2O exchange experiment. The twenty phenyl
protons appear as three sets in which six protons resonate at
Scheme 1 Synthesis of 7b.
Fig. 2 1H NMR spectrum of 7b in CDCl3.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3600–3605 | 3601

View Article Online
Fig. 3 (a) 13C NMR spectrum of 7b in CDCl3 and (b) DEPT 45 spectrum of 7b in CDCl3.
7.16 ppm as multiplet, ten protons resonate as a singlet at
7.06 ppm and other four protons at 6.92 ppm as a doublet (b, c
and d) thus confirming that the chemical environment of the two
meso-carbon atoms are different. The α- (e and f) and β-pyrrolic
CH protons (g, h and i) resonate as a triplet and multiplets at
6.68, 6.42, 6.13, 5.96 and 5.77 ppm, respectively. All together,
the asymmetric chemical environment around the meso-carbon
and the presence of only one pyrrolic NH proton with five pyrro-
lic CH protons prove the composition is 7b having N,α- and
α,β-linkages with meso-carbons instead of 7a. However,
this mode of linkage is different from those found in the
neo-confused and N-confused porphyrin systems, where the
pyrrole units are connected with the meso-carbon atoms through
N,β- and α,β′-linkages to form the macrocycles respectively.11,12
The spatial orientations of hydrogen atoms were assigned by
2D 1H–1H correlation spectroscopy.18 There are two sets of
homonuclear coupling correlations observed in the COSY spec-
trum. The first correlation is between the α and β-pyrrolic CH
protons (f, g and i as in Fig. 2) and the other is between the pyr-
rolic NH with CH protons (e and h).
pyrrolic nitrogens is fused to a meso-carbon atom and is
responsible for the shielding of that particular carbon in the 13C
NMR spectrum. The ortho-protons of the corresponding phenyl
rings are thus largely shielded compared to other phenylic
protons and split into a multiplet and doublet as observed in
the 1H NMR spectral analysis. The seven quaternary carbons
present in 7b can be correctly assigned by subtracting the DEPT
45 (Fig. 3b) from 13C NMR signals. The peaks at 147.42 and
142.70 ppm ( j and k) correspond to the quaternary carbon atoms
of the phenyl groups, which are attached to two different meso-
carbons resonating at 67.97 and 51.86 ppm (o and p) respect-
ively as shown in Fig. 3a. The peaks observed at 139.02, 130.64
and 125.13 ppm (l, m and n) represent the remaining three
1
quaternary pyrrolic carbon atoms. Thus, both H and 13C NMR
data validate the self-condensation of 8 leading to the formation
of 7b.
The explicit structure of the calix[2]pyrrole (7b) has come
from the single crystal X-ray diffraction analysis (Fig. 4).19 The
good quality single crystals were grown by slow evaporation of
n-hexane into CH2Cl2 solution. As confirmed by the spectral
analysis, out of the two pyrrole rings, one of the pyrrolic rings is
in an N,α-linkage with the meso-carbon atom whereas the
second pyrrole ring connects to the meso-carbon atom through
an α,β-linkage (Fig. 4a). Unlike the parent calix[4]pyrrole unit,1
the two pyrrole rings, in order to reduce the steric repulsion,
were found to be in the same plane with two meso-carbon atoms
The fusion of the pyrrolic rings to the meso-carbon atoms
in 7b is further supported by the 13C NMR and DEPT 45
spectral analysis as shown in Fig. 3. The peaks at 67.97 and
51.86 ppm (o and p) in the 13C NMR spectrum (Fig. 3a)
unambiguously explain the different chemical environments for
the two meso-carbon atoms, which indicates one of the
3602 | Org. Biomol. Chem., 2012, 10, 3600–3605
This journal is © The Royal Society of Chemistry 2012

View Article Online
Fig. 4 Single crystal X-ray structure of 7b. (a) Top view, (b) side view, (c) top view with intramolecular hydrogen bonding interactions and (d) 2D
array. The meso-diphenyl groups in (a, and b) and the phenyl groups which are not involved in hydrogen bonding interactions in (d) are omitted for
clarity.
each having phenyl groups pointing above and below the mean
plane18 (Fig. 4b and 4c), and the distortion between the four
phenyl units and the mean plane is 74.38°, 72.35°, 74.72°,
71.71°, respectively.
may undergo BF3·OEt2 assisted hydrolytic cleavage to form the
2-(diphenylmethylene)pyrrolium intermediate 9 which can lose a
proton to afford 2-(diphenylmethylene)pyrrole 10. In the next
step, the lone pair electrons of the nitrogen atom in 10 assists
[3 + 3] cycloaddition with 9 to form a cyclic intermediate 12,
which rapidly undergoes aromatization to yield the more stable
compound 7b.
In summary, we have demonstrated the synthesis, spectral and
structural characterization of a 4,4,9,9-tetraphenyl pyrroloindoli-
zine derivative, which is a structural analogue of calix[2]pyrrole.
The molecule can be considered as the smallest congener of the
corresponding porphyrinogen family, containing only two
pyrrole rings connected through meso-carbon atoms substituted
with bulky phenyl groups. In addition to the spectroscopic evi-
dence, single crystal X-ray analysis reveals the assigned structure
of the molecule. We hope this example will pave the way
towards the synthesis of meso-octaaryl calix[4]pyrroles and
similar porphyrinoids which are unprecedented in the literature.
Attempts towards the synthesis of these macrocycles and studies
to explore the biological activities of the pyrroloindolizine
derivative are currently under way in our group.
Two of the phenyl rings form intramolecular hydrogen
bonding interactions with the pyrrolic π-cloud (C2–H2⋯N1(π)
and C28–H28⋯N2(π)) with distances and angles of 2.81 Å,
127° and 2.83 Å, 127° (Fig. 4c). In addition, 7b also generates
weak intermolecular interactions, where three molecules of 7b
are involved to generate two one-dimensional arrays. The first
array is formed between one of the meso-phenylic C–Hs and the
N2 pyrrolic π-cloud [C4–H4⋯N2(π)], while the meso-phenylic
π-cloud interacts with the N1 pyrrolic α-CH [C14–H14⋯Ph(π)]
and N2 pyrrolic β-CH [C20–H20⋯Ph(π)] with distances and
angles of 2.92 Å, 129°; 2.98 Å, 143° and 2.99 Å, 142°, respect-
ively, to generate the second one-dimensional array.18,20 Com-
bining these two one-dimensional arrays, 7b generates a two-
dimensional supramolecular assembly in the solid state as shown
in Fig. 4d.
The formation of 7b can mechanistically be explained as illus-
trated in Scheme 2. In the presence of a Lewis acid catalyst, 8
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3600–3605 | 3603

View Article Online
Scheme 2 Mechanistic rationale for the formation of 7b.
6 Z.-L. Xue, Z. Shen, J. Mack, D. Kuzuhara, H. Yamada, T. Okujima,
N. Ono, X.-Z. You and N. Kobayashi, J. Am. Chem. Soc., 2008, 130,
16478–16479.
7 D. Kuzuhara, H. Yamada, Z. Xue, T. Okujima, S. Mori, Z. Shen and
H. Uno, Chem. Commun., 2011, 47, 722–724.
8 K. S. Anju, S. Ramakrishnan and A. Srinivasan, Org. Lett., 2011, 13,
2498–2501.
9 (a) G. D. Rodrìguez, T. Torres, D. M. Guldi, J. Rivera, M. A. Herranz
and L. Echegoyen, J. Am. Chem. Soc., 2004, 126, 6301–6313; (b) C.
G. Claessens and T. Torres, Angew. Chem., Int. Ed., 2002, 41, 2561–
2565.
Acknowledgements
Dr A. S. thanks the Directors, NIIST-CSIR and NISER, for
financial support. K. C. G. S. thanks CSIR for a fellowship. We
thank Dr Babu Varghese SAIF, IIT-Chennai for solving the
crystal structure of 7b. We greatly acknowledge Dr
S. Peruncheralathan, NISER for valuable discussions. We also
acknowledge Mrs Viji, and Mr Adarsh, NIIST-CSIR, for record-
ing FAB and NMR spectra.
10 (a) H. Furuta, T. Asano and T. Ogawa, J. Am. Chem. Soc., 1994, 116,
767–768; (b) P. J. Chmielewski, L. Latos-Grażyński, K. Rachlewicz and
T. Glowiak, Angew. Chem., Int. Ed. Engl., 1994, 33, 779–781.
11 K. Fujino, Y. Hirata, Y. Kawabe, T. Morimoto, A. Srinivasan,
M. Toganoh, Y. Miseki, A. Kudo and H. Furuta, Angew. Chem., Int. Ed.,
2011, 50, 6855–6859.
References
12 T. D. Lash, A. D. Lammer and G. M. Ferrence, Angew. Chem., Int. Ed.,
2011, 50, 9718–9721.
1 K. M. Kadish, K. M. Smith and R. Guilard, The Porphyrin Handbook,
Academic Press, San Diego, 2000, ch. 40–46, vol. VI.
13 A. Baeyer, Ber. Dtsch. Chem. Ges., 1886, 19, 2184–2185.
14 (a) P. A. Gale, J. L. Sessler, V. Král and V. Lynch, J. Am. Chem. Soc.,
1996, 118, 5140–5141; (b) P. A. Gale, J. L. Sessler and V. Král, Chem.
Commun., 1998, 1–8; (c) B. Turner, M. Botoshansky and Y. Eichen,
Angew. Chem., Int. Ed., 1998, 37, 2475–2478; (d) S. Depraetere,
M. Smet and W. Dehaen, Angew. Chem., Int. Ed., 1999, 38, 3359–3361;
(e) J. L. Sessler, P. Anzenbacher Jr., J. A. Shriver, K. Jursíková, V.
M. Lynch and M. Marquez, J. Am. Chem. Soc., 2000, 122, 12061–
12062; (f) J. L. Sessler and P. A. Gale, The Porphyrin Handbook, ed.
K. M. Kadish, K. M. Smith and R. Guilard, Academic Press, San Diego,
CA, 2000, vol. 6, pp. 257–278; (g) J. L. Sessler, D. An, W.-S. Cho and
V. Lynch, Angew. Chem., Int. Ed., 2003, 42, 2278–2281.
15 A. Treibs and H. G. Kolm, Justus Liebigs Ann. Chem., 1958, 614, 199–
205.
2 (a) A. Meller and A. Ossko, Monatsh. Chem., 1972, 103, 150–155;
(b) H. Kietaibl, Monatsh. Chem., 1974, 105, 405–418; (c) N. Kobayashi,
J. Chem. Soc., Chem. Commun., 1991, 1203–1205; (d) N. Kobayashi,
T. Ishizaki, K. Ishii and H. Konami, J. Am. Chem. Soc., 1999, 121,
9096–9110; (e) T. Fukuda, J. R. Stork, R. J. Potucek, M. M. Olmstead,
B. C. Noll, N. Kobayashi and W. S. Durfee, Angew. Chem., Int. Ed.,
2002, 41, 2565–2568; (f) C. G. Claessens, D. González-Rodríguez and
T. Torres, Chem. Rev., 2002, 102, 835–853.
3 (a) M. S. Rodríguez-Morgade, S. Esperanza, T. Torres and J. Barberá,
Chem.–Eur. J., 2005, 11, 354–360; (b) T. Torres, Angew. Chem., Int. Ed.,
2006, 45, 2834–2837; (c) J. R. Stork, J. J. Brewer, T. Fukuda, J.
P. Fitzgerald, G. T. Yee, A. Y. Nazarenko, N. Kobayashi and W.
S. Durfee, Inorg. Chem., 2006, 45, 6148–6151; (d) Y. Inokuma and
A. Osuka, Dalton Trans., 2008, 2517–2526; (e) E. Tsurumaki, S. Saito,
K. S. Kim, J. M. Lim, Y. Inokuma, D. Kim and A. Osuka, J. Am. Chem.
Soc., 2008, 130, 438–439; (f) P. J. Brothers, Chem. Commun., 2008,
2090–2102.
16 A. S. Jørgensen, P. Jacobsen, L. B. Christiansen, P. S. Bury, A. Kanstrup,
S. M. Thorpe, S. Bain, L. Nærum and K. Wassermann, Bioorg. Med.
Chem. Lett., 2000, 10, 399–402.
17 K. C. G. Sreedevi, A. P. Thomas, P. S. Salini, S. Ramakrishnan, K.
S. Anju, M. G. D. Holaday, M. L. P. Reddy, C. H. Suresh and
A. Srinivasan, Tetrahedron Lett., 2011, 52, 5995–5999.
4 Y. Inokuma, J. H. Kwon, T. K. Ahn, M.-C. Yoo, D. Kim and A. Osuka,
Angew. Chem., Int. Ed., 2006, 45, 961–964.
5 R. Myśliborski, L. Latos-Grażyński, L. Szterenberg and T. Lis, Angew.
Chem., Int. Ed., 2006, 45, 3670–3674.
18 See the ESI.†
3604 | Org. Biomol. Chem., 2012, 10, 3600–3605
This journal is © The Royal Society of Chemistry 2012

View Article Online
19 Crystal data for 7b (from CH2Cl2–hexane): C34H26N2, Mw = 462.21,
monoclinic, a = 9.0197(6), b = 8.1267(7), c = 16.7735(14) Å, α = 90, β
= 103.407(4), γ = 90°, V = 1196.00(16) Å3, T = 293 (2) K, space group
Pn, Z = 2, Dc = 1.284 mg m−3, μ(Mo-Kα) = 0.075 mm−1, 10540 reflec-
tions collected, 3958 unique (Rint = 0.0275), R1 = 0.0391, wR2 = 0.0963,
GOF = 1.052{I > 2σ(I)}. CCDC 855537 contains the supplementary
crystallographic data for 7b.
20 (a) M. Nishio, Phys. Chem. Chem. Phys., 2011, 13, 13873–13900;
(b) H. Takahashi, S. Tsuboyama, Y. Umezawa, K. Honda and M. Nishio,
Tetrahedron, 2000, 56, 6185–6191.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3600–3605 | 3605