11020
J. Am. Chem. Soc. 1999, 121, 11020-11021
Calix[4]pyrroles Containing Deep Cavities and Fixed
Walls. Synthesis, Structural Studies, and Anion
Binding Properties of the Isomeric Products Derived
from the Condensation of p-Hydroxyacetophenone
and Pyrrole
†
†
Pavel Anzenbacher, Jr., Karolina Jurs ´ı kov a´ ,
†
‡
,†
Vincent M. Lynch, Philip A. Gale, and Jonathan L. Sessler*
Department of Chemistry and Biochemistry
The UniVersity of Texas at Austin, Austin, Texas 78712-1167
Department of Chemistry, UniVersity of Southampton
Southampton SO17 1BJ, U.K.
ReceiVed September 3, 1999
The inclusion chemistry of receptors with extended cavities
has attracted the attention of an increasing number of research
1
groups. Extension of the cavity of a preexisting receptor molecule
may confer new binding properties on the molecule and/or
modulate the existing affinity of the receptor for guest species.
Our recent discovery that calix[4]pyrroles (e.g., 1), a class of
2
tetrapyrrolic macrocycle known for over a century, are effective
3
and selective receptors for anions and, to a lesser extent, neutral
4
guest species led us to produce a number of calixpyrroles that
5
6
have found application in anion sensing and separation tech-
nologies. Additionally, we have found that it is possible to tune
the anion binding affinity of these receptors by substitution at
either the â-positions of the pyrrole rings or the meso-carbons of
the calixpyrrole3 or by fusing a calixarene scaffold onto the basic
,7
Figure 1. Structures of calix[4]pyrroles (2, Ar ) 4-hydroxyphenyl; 3,
Ar ) 4-methoxyphenyl). Inequivalent CH positions are labeled with
different letters (thus in RRRR all the CH protons are equivalent while
in RRRâ there are four inequivalent sets of protons, a, b, c, and d).
8
calixpyrrole framework. Separately, Eichen and co-workers have
succeeded in preparing calix[4]pyrroles with flat, extended aryl
9
“
wings” as well as “expanded” calix[6]pyrroles. In this Com-
munication, we report the first examples of a new class of calix-
4]pyrroles containing deep cavities and fixed walls. These
[
lower affinities for small anions, specifically Cl- and H
2 4
PO
-,
systems, represented by prototypical systems 2 and 3, are easily
obtained from the condensation of p-hydroxyacetophenone with
pyrrole.1 Surprisingly and unexpectedly, these systems show
in acetonitrile-water (99.5:0.5) than do simple unsubstituted
calix[4]pyrroles such as 1. On the other hand, increased selectivi-
ties and other binding effects ascribable to the “walls” of the
cavities are observed.
0,11
†
The University of Texas at Austin.
†
Calixpyrrole 2 was prepared using a modification of standard
University of Southampton.
literature methods.12 Briefly, p-hydroxyacetophenone (13.62 g,
(
1) For representative examples of extended cavity calixarenes and resor-
cinarenes, see: (a) MacGillivray, L. R.; Atwood, J. L. Chem. Commun. 1999,
100 mmol), pyrrole (6.71 g, 100 mmol), and methanesulfonic acid
1
81-182. (b) Ma, S. H.; Rudkevich, D. M.; Rebek, J., Jr. J. Am. Chem. Soc.
1
998, 120, 4977-4981. (c) Arduini, A.; Pochini, A.; Rizzi, A.; Sicuri, A. R.;
(4.81 g, 50 mmol) were dissolved in methanol (300 mL) and
stirred at room temperature for 6 h under an inert atmosphere.
After this mixture was neutralized with ammonia gas and passed
through a short silica gel precolumn, the desired calix[4]pyrrole
was isolated, as a mixture of four configurational isomers, via
column chromatography (silica gel, 6-8% methanol in chloroform
v/v) in 62% yield. The relative yields of these latter isomers,
denoted RâRâ, RRââ, RRRâ, and RRRR to indicate the relative
position of the bulky substituted phenyl substituent (cf. Figure
Ugozzoli, F.; Ungaro, R. Tetrahedron 1992, 48, 905-912.
(
(
2) Baeyer A. Ber. Dtsch. Chem. Ges. 1886, 19, 2184-2185.
3) Gale, P. A.; Sessler, J. L.; Kr a´ l, V.; Lynch, V. J. Am. Chem. Soc. 1996,
1
1
18, 5140-5141. Gale, P. A.; Sessler, J. L.; Kr a´ l, V. Chem. Commun. 1998,
-8.
(
4) Allen, W. E.; Gale, P. A.; Brown, C. T.; Lynch, V. M.; Sessler, J. L.
J. Am. Chem. Soc. 1996, 118, 12471-12472.
(
5) (a) Miyaji H.; Anzenbacher, P., Jr.; Sessler, J. L.; Bleasdale, E. R.;
Gale, P. A. Chem. Commun. 1999, 1723-1724. (b) Gale, P. A.; Twyman, L.
J.; Handlin, C. I.; Sessler, J. L. Chem. Commun. 1999, 1851-1852.
(
6) Sessler, J. L.; Gale, P. A.; Genge, J. W. Chem. Eur. J. 1998, 4, 1095-
1), were on the order of <5%, 25%, 30%, and 45%, respectively.
1
099.
7) Gale, P. A.; Sessler, J. L.; Allen, W. E.; Tvermoes, N. A.; Lynch, V.
M. Chem. Commun. 1997, 665-666.
8) (a) Gale, P. A.; Sessler, J. L.; Lynch, V.; Sansom, P. I. Tetrahedron
(
They were readily separated from one another during the
chromatographic purification and, as would be expected on the
basis of considerations of relative polarity, found to elute in the
same order as the atropoisomers of 2,2′,2′′,2′′′-substituted tetra-
(
Lett. 1996, 37, 7881-7884. (b) Gale, P. A.; Genge, J. W.; Kr a´ l, V.; McKervey,
M. A.; Sessler, J. L.; Walker, A. Tetrahedron Lett. 1997, 38, 8443-8444.
(
9) Turner, B.; Botoshansky, M.; Eichen, Y. Angew. Chem., Int. Ed. 1998,
phenylporphyrins, namely (in order of decreasing R ) RâRâ >
f
3
7, 2475-2478.
RRââ > RRRâ > RRRR.13 Once isolated, the individual isomers
of 2 were converted to their respective 4-methoxyphenyl con-
(
10) The first examples of unsymmetrical, as opposed to the present deep-
cavity, calixpyrroles were produced by the Russian chemists Chelintzev and
Tronov. Among other accomplishments, they isolated a pure sample of a single
configurational isomer of meso-tetramethyltetraethylcalix[4]pyrrole: (a) Che-
lintzev, V. V.; Tronov, B. V. J. Russ. Phys. Chem. Soc. 1916, 48, 105-155.
(12) . (a) Rothemund, P.; Gage, C. L. J. Am. Chem. Soc. 1955, 77, 3340-
3342. (b) Brown, W. H.; Hutchinson, B. J.; MacKinnon, M. H. Can. J. Chem.
1971, 49, 4017-4022.
(13) (a) Collman, J. P.; Gagne, R. R.; Reed, C. A.; Halbert, T. R.; Lang,
G.; Robinson, W. T. J. Am. Chem. Soc. 1975, 97, 1427-1439. (b) Lindsey,
J. J. Org. Chem. 1980, 45, 5215-5215. (c) Rose, E.; Cardon-Pilotaz, A.;
Quelquejeu, M.; Bernard, N.; Kossanyi, A. J. Org. Chem. 1995, 60, 3919-
3920.
(
b) Chelintzev, V. V.; Tronov, B. V. J. Russ. Phys. Chem. Soc. 1916, 48,
1
197-1209.
(11) Early studies of unsymmetrical meso-aryl-substituted calix[4]pyrroles
were presented in the following: Sessler, J. L.; Anzenbacher, P., Jr.; Jurs ´ı kov a´ ,
K.; Miyaji, H.; Genge, J. W.; Tvermoes, N. A.; Allen, W. E.; Shriver, J. A.;
Gale, P. A.; Kr a´ l, V. Pure Appl. Chem. 1998, 70, 2401-2408.
1
0.1021/ja993195n CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/13/1999