Synthesis of calix[3]dipyrrins by a modified Lindsey protocol

Article abstract of DOI:10.1002/anie.200604882

(Figure Presented) Bowled over: Calix[3]dipyrrins were synthesized from pyrrole and aryl aldehyde precursors by the Lindsey protocol, modified by the presence of a small amount of water. These bowl-shaped macrocycles can accommodate three metal (M) ions such as Ni^II and Cu^II in a hexagonal M₃O₃ manner (see structure; Cu green, N blue, O red, C black).

Full text of DOI:10.1002/anie.200604882

Communications
DOI: 10.1002/anie.200604882
Porphyrinoids
Synthesis of Calix[3]dipyrrins by a Modified Lindsey Protocol**
Mitsunori Inoue, Chusaku Ikeda, Yuji Kawata, Sundararaman Venkatraman, Ko Furukawa, and
Atsuhiro Osuka*
The Lindsey protocol, a one-pot two-step reaction between
pyrrole and an aldehyde, has been extensively used for the
synthesis of porphyrins[1] and has been revealed in recent
years to provide various other pyrrolic macrocycles, such as
corroles,[2] sapphyrins,[3] N-confused porphyrins,[4] and meso-
aryl-substituted expanded porphyrins,[5] depending upon the
concentrations, additives, reaction medium, stoichiometry of
the pyrrole and aryl aldehyde, and structures of the substrates.
The Lindsey protocol usually requires anhydrous conditions
because of the dehydrative nature of the first condensation
reaction between pyrrole and the aldehyde and may be
influenced by the presence of water.[1] Recently, we reported
that novel heptaphyrins bearing direct pyrrole–pyrrole link-
ages were formed from pentafluorobenzaldehyde and pyrrole
by the Lindsey protocol under aqueous conditions in the
presence of a sodium dodecyl sulfate micelle.[6] Herein, we
report the synthesis of new hexapyrrolic macrocycles, cal-
ix[3]dipyrrins, in modest yields by a modified Lindsey
protocol in the presence of a small amount of water. Whereas
calix[4]pyrroles and calix[n]phyrins have been shown to serve
as effective anion receptors,[7,8] calix[3]dipyrrins have preor-
ganized coordination sites that can accommodate three
cations in a symmetric triangular fashion.
X-ray diffraction analysis, which revealed a trimetallated
calix[3]dipyrrin macrocycle consisting of three planar dipyrrin
segments connected by aryl- and hydroxy-substituted meth-
ylene units (Figure 1).[9] The three NiII atoms are located at
the apexes of an equilateral triangle and are bridged by three
m-alkoxo oxygen atoms to form a Ni3O3 hexagonal core. The
NiII atoms are each coordinated by two pyrrolic N atoms with
The NiII complex of tetrakis(4-methoxycarbonylphenyl)-
porphyrin was prepared by treating a solution of pyrrole and
4-methoxycarbonylbenzaldehyde in CH2Cl2 with trifluoro-
acetic acid (TFA) for 2 h. Oxidation of the mixture with 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) for 1 h and
subsequent metallation with [Ni(acac)2] (acac: acetylaceto-
nate) provided the expected porphyrin product (15%) as well
as a red product that eluted slowly on a silica gel column. This
side product was assigned as calix[3]dipyrrin 1 on the basis of
[*] M. Inoue, Dr. C. Ikeda, Y. Kawata, Dr. S. Venkatraman,
Prof. Dr. A. Osuka
Department of Chemistry
Graduate School of Science, Kyoto University and
Core Research for Evolutional Science andTechnology (CREST)
Japan Science andTechnology Agency
Sakyo-ku, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3970
E-mail: osuka@kuchem.kyoto-u.ac.jp
Homepage: http://kuchem.kyoto-u.ac.jp/shuyu/index.html
Dr. K. Furukawa
Institute for Molecular Science
Myodaiji, Okazaki 444-8585 (Japan)
[**] This work was partly supportedby a grant-in-aid(B no. 17350017)
from the Ministry of Education, Culture, Sports, Science, and
Technology, Japan.
Figure 1. X-ray crystal structure of 1: a) top view andb) side view.
Solvent molecules are omittedfor clarity. Thermal ellipsoids are shown
at the 50% probability level.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
2306
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 2306 –2309

Angewandte
Chemie
Table 1: Preparation of calix[3]dipyrrins under the modified Lindsey
conditions.
Ni–N distances of 1.80–1.81 Š and two bridging O atoms with
Ni–O distances of 1.90–1.91 Š in a square-planar arrange-
ment. The metallated dipyrrin segments are tilted by approx-
imately 1418 relative to one another to form a bowl-shaped
macrocycle.
Entry Aryl aldehyde
Calix[3]dipyrrin
Yield [%]
calix[3]di- porphyrinato-
pyrrinato- nickel(II)[b]
nickel(II)[a]
High-resolution electrospray ionization time-of-flight
(HR ESI-TOF) mass spectrometry revealed parent ion
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
4-MeOOCC6H4CHO
1
4
5
6
7
8
9
10
11
–
–
–
–
–
–
–
–
–
15
13
11
8
4-NCC6H4CHO
4-O2NC6H4CHO
4-F3CC6H4CHO
4-FC6H4CHO
4-ClC6H4CHO
4-BrC6H4CHO
3-O2NC6H4CHO
3-CF3C6H4CHO
3,5-(CF3)2C6H3CHO
3,5-Cl2C6H3CHO
2,6-Cl2C6H3CHO
2-O2NC6H4CHO
C6H5CHO
4-MeC6H4CHO
4-MeOC6H4CHO
3,5-tBu2C6H3CHO
2,4,6-Me3C6H2CHO
trace
trace
trace
trace
trace
trace
4.1
trace
trace
4.9
0
0
16
11
2.4
18
0
peaks
for
1
at
m/z 1513.1527
(calcd
for
[(C78H54N6O15Ni3Na)]+ = 1513.1583), consistent with its struc-
7.5
1
ture. In the H NMR spectra, most of the signals for 1 are
1.4
5.5
2.1
3.9
4.0
trace
0
0
0
0
0
consistent with the structure, but the aromatic protons of the
meso-substituted aryl groups appeared as rather broad signals
at d = 8.08, 7.54, and 7.39 ppm at 258C, suggesting the
restricted rotation of these aryl groups. At À208C, these
signals split into a pair of sharp doublets at d = 8.11 and
8.04ppm ( J = 8.3 Hz), and d = 7.54and 7.37 ppm ( J = 8.2 Hz).
By simulating the temperature-dependent spectral profiles, a
rotational energy barrier of 8.5 kcalmolÀ1 was determined
(see the Supporting Information).
Importantly, [Ni(acac)2] should be added after the con-
densation/annulation reaction; the Lindsey protocol did not
afford any calix[3]dipyrrin product in the presence of the
metal salt. The source of the oxygen atoms in 1 was elucidated
by examining the reaction in CH2Cl2 in the presence of
variable amounts of water or with O2 bubbling. Almost no
influence was observed when dry O2 was bubbled through the
solution, but the yield of 1 varied upon the amount of water
present in CH2Cl2. In fact, the yield of 1 was found to be
consistently more than 8% in the presence of a small amount
of water (c(H2O) ꢀ 6.7 ” 10À3 m). Even under the anhydrous
conditions at the start of the reaction, the acid-catalyzed
condensation of an aldehyde and pyrrole liberates a small
amount of water, which seemingly promotes the formation of
1. The yield of isolated 1 was optimal (15%) at a concen-
tration of 6.7 ” 10À3 m of water but dropped sharply at higher
concentrations (see the Supporting Information). In the
presence of 3-Š molecular sieves as a dehydrating agent,
the reaction provided only the porphyrin and none of the
calix[3]dipyrrin 1, which strongly suggests the importance of
adventitious water for the formation of 1. The involvement of
water for the formation of 1 was confirmed by an experiment
in the presence of H218O, which gave partially 18O-labeled
product (Supporting Information).
Under these optimized conditions, a range of calix[3]di-
pyrrins were obtained in moderate to low yields from aryl
aldehydes bearing electron-withdrawing groups at the 4-
position (Table 1, entries 1–7) or at the 3-position (entries 8
and 9). On the other hand, no calix[3]dipyrrins were obtained
either from 3,5-disubstituted (Table 1, entries 10 and 11) or 2-
substituted aryl aldehydes (entries 12 and 13), probably owing
to steric hindrance. Benzaldehyde and aryl aldehydes with
electron-donating groups also did not furnish calix[3]dipyrrin
products (Table 1, entries 14–18).
0
0
0
[a] Yieldof isolatedcalix[3]idpyrrinatonickel(II) complex. [b] Yieldof
isolatedporphyrinatonickel(II) complex.
pointing toward the inside of the cavity with O–O distances of
4.04, 4.14, and 4.17 Š (Figure 2).[10] The dihedral angles of the
dipyrrin segments (ca. 1078) in 2 are smaller than those in 1.
The macrocycle becomes more distorted upon demetallation
as indicated by the larger mean plane deviation of 36 atoms of
macrocycle 2 (0.622 Š) as compared to that of 1 (0.389 Š).
Similar to the case of 1, the rotational barrier of the aryl
substituents at the meso position of the dipyrromethene was
determined to be 6.2 kcalmolÀ1 (Supporting Information).
The triangular geometry of 2 appeared to offer an ideal
situation for the observation of unique competing magnetic
interactions, namely spin frustration, in its paramagnetic
metal complexes.[12,13] This expectation led us to prepare the
tris-CuII complex 3 by heating a solution of 2 in CHCl3 with an
excess amount of Cu(OAc)2 at 508C (quantitative reaction).
The structure of 3 was confirmed by X-ray crystallography to
be essentially the same as that of 1 (Figure 3). The three CuII
atoms are coordinated by two pyrrolic N atoms with Cu–N
distances of 1.89–1.91 Š and two bridging alkoxo O atoms
with a Cu–O distance of 1.94Š, and a mean plane deviation
of 0.393 Š.[11]
The variable-temperature magnetic susceptibility of 3 was
measured over the range 2–300 K (Figure 4). At 300 K the
complex 3 exhibits cMT= 1.02 emuKmolÀ1, which roughly
corresponds to three independent CuII ions but is smaller than
the expected value of 1.20 emuKmolÀ1, which indicates some
antiferromagnetic interaction. As the temperature was low-
ered, the cMT value gradually decreased and reached a value
of 0.35 emuKmolÀ1 at 2 K, which was lower than the spin-
only value for a single independent CuII ion of S = 1/2. Such
temperature-dependent behavior indicates strong antiferro-
magnetic interactions among the three CuII ions, and the
observed lower cMT value suggests an additional intermolec-
In contrast to the considerable robustness of NiII-porphyr-
ins toward treatment with acid, demetallation of 1 with TFA
was facile and quantitative to provide free base 2. The
structure of 2 was confirmed by X-ray diffraction analysis,
which revealed that the three hydroxy groups at the sp3-
hybridized meso positions adopt equatorial positions, hence
Angew. Chem. Int. Ed. 2007, 46, 2306 –2309
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2307

Communications
Figure 3. X-ray crystal structure of 3: a) top view andb) side view.
Solvent molecules are omittedfor clarity. Thermal ellipsoids are shown
at the 50% probability level.
Figure 2. X-ray crystal structure of 2: a) top view andb) side view.
Solvent molecules are omittedfor clarity. Thermal ellipsoids are shown
at the 50% probability level.
ular antiferromagnetic interaction, as has been reported for
similar triangular tris-CuII compounds.[13] The mean g value
was determined to be 2.097 by ESR spectroscopy in frozen
toluene at 20 K, and the ESR spectrum was consistent with a
S = 1/2 system, which was considered the ground state of the
frustration system (Supporting Information). Given that the
magnetic exchange interactions among the three CuII ions is
the same, the least-squares fit of the experimental data
through a triangular model[12] with an intermolecular inter-
action q based on the mean-field approximation gave a J
value of À44.1 cmÀ1 for the intramolecular interaction and a q
value of À0.99 K (qkB = 0.69 cmÀ1) for the intermolecular
interaction.
In summary, calix[3]dipyrrins were synthesized in moder-
ate to low yields as novel pyrrolic macrocycles from appro-
priate precursors by the Lindsey protocol under non-anhy-
drous conditions. These calix[3]dipyrrin macrocycles accom-
modate three metal ions such as NiII and CuII ions in a
hexagonal M3O3 manner. The tris-CuII complex 3 shows
typical competing spin–spin interactions as revealed by
temperature-dependent magnetic susceptibility measure-
ments. Studies concerning the further use of these novel
Figure 4. Temperature-dependent magnetic susceptibility of 3
*
(
^
observed; calculated).
pyrrolic macrocycles are currently in progress in our labo-
ratory.
Received: December 2, 2006
Published online: February 19, 2007
Keywords: copper · macrocyclic ligands · nickel ·
.
porphyrinoids · synthetic methods
2308 www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 2306 –2309

Angewandte
Chemie
Ed. 2000, 39, 1055; b) C. Bucher, D. Seidel, V. Lynch, V. Krµl,
J. L. Sessler, Org. Lett. 2000, 2, 3103; c) C. Bucher, R. S.
Zimmerman, V. Lynch, V. Krµl, J. L. Sessler, J. Am. Chem.
[1] a) J. S. Lindsey, H. C. Hsu, I. C. Schreiman, Tetrahedron Lett.
1986, 27, 4969; b) J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C.
Kearney, A. M. Marguerettaz, J. Org. Chem. 1987, 52, 827; c) a
BF3-EtOH cocatalyst was reported to be advantageous for the
synthesis of sterically hindered porphyrins, see: J. S. Lindsey,
R. W. Wanger, J. Org. Chem. 1989, 54, 828.
[2] a) Z. Gross, N. Galili, I. Saltsman, Angew. Chem. 1999, 111, 1530;
Angew. Chem. Int. Ed. 1999, 38, 1427; b) R. Paolesse, S. Mini, F.
Sagone, T. Boschi, L. Jaquinod, D. J. Nurco, K. M. Smith, Chem.
Commun. 1999, 1307; c) D. T. Gryko, Chem. Commun. 2000,
2243.
´
Soc. 2001, 123, 2099; d) B. Dolensky, J. Kroulík, V. Krµl, J. L.
ˇ
ˇ
Sessler, H. Dvorµkovµ, P. Bour, M. Bernµtkovµ, C. Bucher, V.
Lynch, J. Am. Chem. Soc. 2004, 126, 13714.
[9] Crystallographic data for 1: C81H58Cl5N6Ni3O15, Mw = 1708.71,
monoclinic, space group P21/c (no. 14), a = 11.4510(17), b =
20.120(3), c = 31.920(5) Š, a = 90, b = 98.336(3), g = 908, V=
7276.6(19) Š3, 1calcd = 1.560 gcmÀ3
, Z = 4, R1 (I > 2.0s(I)) =
0.0773, wR2 (all data) = 0.2368, GOF = 1.079 (I > 2.0s(I)).
[10] Crystallographic data for 2: C80H62Cl2N6O16, Mw = 1434.26,
´
¯
[3] P. J. Chmielewski, L. Latos-Graz˙ynski, K. Rachlewicz, Chem.
triclinic, space group P1 (no. 2), a = 12.018(4), b = 17.091(7),
Eur. J. 1995, 1, 68.
c = 19.587(7) Š,
a = 93.987(14),
b = 102.889(13),
g =
95.224(13)8, V= 3888(3) Š3, 1calcd = 1.225 gcmÀ3, Z = 2, R1 =
0.0985 (I > 2.0s(I)), wR2 (all data) = 0.3204, GOF = 1.027 (I >
2.0s(I)).
´
[4] a) P. J. Chmielewski, L. Latos-Graz˙ynski, K. Rachlewicz, T.
Glowiak, Angew. Chem. 1994, 106, 805; Angew. Chem. Int. Ed.
Engl. 1994, 33, 779; b) H. Furuta, T. Asano, T. Ogawa, J. Am.
Chem. Soc. 1994, 116, 767.
[11] Crystallographic data for 3: C97H69Cl3Cu3N6O16, Mw = 1871.55,
¯
[5] a) M. G. P. M. S. Neves, R. M. Martins, A. C. TomØ, A. J. D.
Silvestre, A. M. S. Silva, V. FØlix, M. G. B. Drew, J. A. S.
Cavaleiro, M. G. B. Drew, Chem. Commun. 1999, 385; b) J.-Y.
Shin, H. Furuta, K. Yoza, S. Igarashi, A. Osuka, J. Am. Chem.
Soc. 2001, 123, 7190; c) S. Shimizu, J.-Y. Shin, H. Furuta, R.
Ismael, A. Osuka, Angew. Chem. 2003, 115, 82; Angew. Chem.
Int. Ed. 2003, 42, 78; d) A. Krivokapic, A. R. Cowley, H. L.
Anderson, J. Org. Chem. 2003, 68, 1089; e) S. Shimizu, N.
Aratani, A. Osuka, Chem. Eur. J. 2006, 12, 4909; f) X.-J. Zhu, S.-
T. Fu, W.-K. Wong, J.-P. Guo, W.-Y. Wong, Angew. Chem. 2006,
118, 3222; Angew. Chem. Int. Ed. 2006, 45, 3150.
[6] S. Hiroto, H. Shinokubo, A. Osuka, J. Am. Chem. Soc. 2006, 128,
6568.
[7] For the chemistry of calix[n]pyrroles and calix[n]bipyrroles, see:
a) P. A. Gale, J. L. Sessler, V. Krµl, Chem. Commun. 1998, 1;
b) J. L. Sessler, D. An, W.-S. Cho, V. Lynch, Angew. Chem. 2003,
115, 2380; Angew. Chem. Int. Ed. 2003, 42, 2278.
triclinic, space group P1 (no. 2), a = 11.668(7), b = 19.070(12),
c = 19.801(12) Š, a = 69.599(9), b = 87.517(10), g = 84.319(10)8,
V= 4109(4) Š3, 1calcd = 1.513 gcmÀ3
, Z = 2, R1 = 0.0982 (I >
2.0s(I)), wR2 (all data) = 0.3117, GOF = 1.060 (I > 2.0s(I)).
CCDC-627140 (1), CCDC-627141 (2), and CCDC-627142 (3)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[12] O. Kahn, Chem. Phys. Lett. 1997, 265, 109.
[13] a) R. Clerac, F. A. Cotton, K. R. Dunbar, E. A. Hillard, M. A.
Petrukhina, B. W. Smucker, C. R. Acad. Sci. Ser. IIc: Chim. 2001,
4, 315; b) M. Kodera, Y. Tachi, T. Kita, H. Kobushi, Y. Sumi, K.
Kano, M. Shiro, M. Koikawa, T. Tokii, M. Ohba, H. Okawa,
Inorg. Chem. 2000, 39, 226; c) H. Lꢀpez-Sandoval, R. Coun-
treras, A. Escuer, R. Vicente, S. Bernꢁs, H. Nꢂth, G. J. Leigh, N.
Barba-Behrens, J. Chem. Soc. Dalton Trans. 2002, 2648.
[8] a) V. Krµl, J. L. Sessler, R. S. Zimmerman, D. Seidel, V. Lynch, B.
Andrioletti, Angew. Chem. 2000, 112, 1097; Angew. Chem. Int.
Angew. Chem. Int. Ed. 2007, 46, 2306 –2309
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 2309