Synthesis of novel expanded calixphyrins: Anion binding properties of a calix[6]phyrin with a deep cavity [21]

Full text of DOI:10.1021/ja005842c

J. Am. Chem. Soc. 2001, 123, 2099-2100
2099
Scheme 1
Synthesis of Novel Expanded Calixphyrins: Anion
Binding Properties of a Calix[6]phyrin with a Deep
Cavity
Christophe Bucher,† Rebecca S. Zimmerman,† Vincent Lynch,†
Vladimir Kra´l,‡ and Jonathan L. Sessler*,†
Department of Chemistry and Biochemistry
UniVersity of Texas at Austin, Austin, Texas 78712-1167
Department of Analytical Chemistry, Technical UniVersity
166 10 Prague 6, Czech Republic
yield).7 While the yield of 2 is low, the ready availability of the
starting materials allows this key precursor to be made easily in
g10 g batches.
ReceiVed December 1, 2000
Initial attempts to react tripyrrane 2 with benzaldehyde in the
presence of various Brønsted or Lewis acids proved unproductive.
In our hands, the only products obtained were ones in which the
integrity of the starting polypyrrole was degraded. Considering
that these observations could reflect the fact that tripyrrane 2 is
inherently unstable in the presence of acid, pentafluorobenzal-
dehyde was chosen as the reaction partner; this electron-deficient
aryl aldehyde is known to react with pyrrole derivatives in the
absence of any catalyst.8 Condensation of 2 with 4 in dichlo-
romethane at room temperature followed by DDQ oxidation gave
calix[6]phyrin 1 in ca. 10% yield (Scheme 2, Ar ) C6F5).
Chemical hybrids of the porphyrins and calixpyrroles, calix-
[n]phyrins, are polypyrrolic macrocycles that contain at least one
sp3 hybridized meso-like bridging carbon atom. While examples
of calix[4]phyrin derivatives, represented by such classic structures
as the phlorins,1 isoporphyrins,2 5,10- or 5,15-dihydroporphyrins,3
and porphomethenes,4 abound, the chemistry of higher order calix-
[n]phyrins (n > 4) remains virtually unexplored.3f,5 Recently, we
reported the synthesis of calix[6]- and calix[9]phyrin, macrocycles
that contain a succession of conjugated dipyrromethene subunits
linked via sp3 hybridized meso-like bridging carbon atoms.3f We
have now found that, by using appropriate acyclic polypyrrolic
precursors, it is possible to modify the ratio of oxidized to non-
oxidized meso-like carbon atoms in higher order calix[n]phyrins
as well as the distribution of these bridging centers within the
macrocyclic skeleton. Specifically, we report here the synthesis
of 5,5-10,10-20,20-25,25-octamethylcalix[6]phyrin 1, obtained
from 5,5,10,10-tetramethyltripyrrane 2, and show that this non-
planar species acts as an anion receptor both in solution and in
the solid sate.
Scheme 2
The synthesis of tripyrrane 2 is shown in Scheme 1.6 It is
obtained from the TFA acid-catalyzed condensation of pyrrole
and acetone. Optimal conditions involved stirring at room
temperature for 2 h followed by the addition of triethylamine.
Removal of excess pyrrole by distillation followed by column
chromatographic purification (silica gel; hexane-dichloromethane
eluent) yielded 2 in an approximate yield of 5%, along with
substantial quantities of the known dipyrromethane 3 (ca. 25%
Compound 1 displayed spectroscopic properties in accord with
the proposed structure and was characterized by X-ray diffraction
analysis. The resulting Ortep views (Figure 1) revealed the
† University of Texas at Austin.
‡ Technical University, Prague.
(1) For examples of phlorins, see: Sugimoto, H. J. Chem. Soc., Dalton
Trans. 1982, 1169. Setsune, J.; Ikeda, T.; Iida, T.; Kitao, T. J. Am. Chem.
Soc. 1988, 110, 6572. Segawa, H.; Azumi, R.; Shimidzu, T. J. Am. Chem.
Soc. 1992, 114, 7564. Setsune, J.; Wada, K.; Higashino, H. Chem. Lett. 1994,
213. Jiang, X.; Nurco, D. J.; Smith, K. M. Chem. Commun. 1996, 1759.
Krattinger, B.; Callot, H. J. Eur. J. Org. Chem. 1999.
(2) For examples of isoporphyrins, see: Dolphin, R.; Felton, R. H.; Borg,
D. C.; Fajer, C. J. Am. Chem. Soc. 1970, 92, 743. Fuhrhop, J.-H.;
Lumbantobing, T. Tetrahedron Lett. 1970, 32, 2815. Xie, H.; Smith, K. M.
Tetrahedron Lett. 1992, 33, 1197. Barkigia, K. M.; Renner, M. W.; Xie, H.;
Smith, K. M.; Fajer, J. J. Am. Chem. Soc. 1993, 115, 7894.
(3) 5,10-Dihydroporphyrins: (a) Krattinger B.; Callot, H. J. Tetrahedron
Lett. 1998, 39, 1165. (b) Krattinger, B.; Callot, H. J. Eur. J. Org. Chem. 1999,
1857. (c) Bucher, C.; Seidel, D.; Lynch, V.; Kra´l, V.; Sessler, J. L. Org. Lett.
2000, 2, 3103. For examples of 5,15-dihydroporphyrins, see: (d) Buchler, J.
W.; Lay, K. L.; Smith, P. D.; Scheidt, W. R.; Rupprecht, G. A.; Kenny, J. E.
J. Organomet. Chem. 1976, 110, 109. (e) Bonomo, L.; Solari, E.; Scopelliti,
R.; Floriani, C.; Re, N. J. Am. Chem. Soc. 2000, 122, 5312. (f) Kra´l, V.;
Sessler, J. L.; Zimmerman, R. S.; Seidel, D.; Lynch, V.; Andrioletti, B. Angew.
Chem., Int. Ed. 2000, 39, 1055. (g) Harmjanz, M.; Gill, H. S.; Scott, M. J. J.
Am. Chem. Soc. 2000, 122, 10476.
(4) For examples of porphomethenes, see: Benech, J.-M.; Bonomo, L.;
Solari, E.; Scopelliti, R.; Floriani, C. Angew. Chem., Int. Ed. 1999, 38, 1957
and references therein.
(5) Khoury, R. G.; Jaquinod, L.; Nguyen, L. T.; Smith, K. M. Heterocycles
1998, 47, 113. Wytko, J. A.; Michels, M.; Zander, L.; Lex, J.; Schmickler,
H.; Vogel, E. J. Org. Chem. 2000, 65, 8709.
Figure 1. Ortep10 views of 1‚H2O showing the heteroatom labeling
scheme. Hydrogen bonding interactions are indicated by dashed lines.
presence of a water molecule bound to the macrocycle through
two N‚‚‚Hw and two N-H‚‚‚OW intramolecular interactions.
Considering the deep cavity structure observed in the solid state
as well as the existence of two calixpyrrole-like pyrrole moieties
pointing in toward the center of the cleft, it was considered likely
that macrocycle 1 would act as an efficient anion receptor.
(7) Brown, W. H.; French, W. N. Can. J. Chem. 1958, 36, 371. Littler, B.
J.; Miller, M. A.; Hung, C.-H.; Wagner, R. W.; O’Shea, D. F.; Boyle, P. D.;
Lindsey, J. S. J. Org. Chem. 1999, 64, 1391.
(8) Gross, Z.; Galili, N.; Simkhovitch, L.; Saltsman, I.; Botoshansky, M.;
Bla¨ser, D.; Boese, R.; Goldberg, I. Org. Lett. 1999, 1, 599.
(6) Although tripyrrane 2 appears to be a new compound, analogous
materials have been reported; see: Bru¨ckner, C.; Sternberg, E. D.; Boyle, R.
W.; Dolphin, D. Chem. Commun. 1997, 1689. Ka, J.-W.; Lee, C.-H.
Tetrahedron Lett. 2000, 41, 4609.
10.1021/ja005842c CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/10/2001

2100 J. Am. Chem. Soc., Vol. 123, No. 9, 2001
Communications to the Editor
However, perhaps as a consequence of the strongly bound water
located inside the cavity, little evidence of anion binding was
observed upon the addition of various anions (e.g., Cl-, Br-, I-,
NO3-, HSO4-). On the other hand, as has proved to be the case
with a variety of other polypyrrolic macrocycles, anion binding
was observed following protonation.9
The monoprotonated form of 1, [1‚H]+‚Cl-, was obtained in
the form of single crystals via the slow evaporation of a
dichloromethane solution previously washed with aqueous 1 N
HCl. The resulting X-ray diffraction structure (Figure 2) revealed
Figure 3. Absorpsion spectra of [1‚2H]2+, generated by the addition of
90 molar equiv of H2SO4‚30% SO3 to ca. 9.8 × 10-3 mM solutions of 1,
in the absence and presence of anions. The concentrations shown
correspond to ones at which the addition of further molar equivalents
induced no additional spectral changes.
Figure 2. Ortep10 views of [1‚H]+‚Cl- showing the heteroatom labeling
scheme. N-H‚‚‚Cl intramolecular interactions are indicated by dashed
lines. The bound chloride anion is disordered.
of H2SO4‚30% SO3 to 1, revealed that hydrogen sulfate is bound
with a Ka for 1:1 complexation of 3500 ( 390 M-1. On this basis12
it is estimated that, to the extent it could be prepared in the absence
of a coordinating counteranion, receptor [3‚2H]2+ would bind I-
in acetone solution with an affinity constant Ka ) 8 × 107 M-1
.
that, as expected, one of the dipyrromethene subunits is protonated
and that the chloride counteranion is located in the cavity,
hydrogen bonded by both calixpyrrole-like NHs (Figure 2, N2-
H‚‚‚Cl and N5-H‚‚‚Cl).
While not established by the present solution-phase experiments,
in analogy to what is seen in the solid state, it is assumed that
1:1 binding of iodide anion takes place within the positively
charged, NH hydrogen bond donor rich cavity.
Current work is focused on probing in greater detail the
molecular recognition characteristics of calix[6]phyrin 1 and in
using analogous strategies to prepare other calix[n]phyrin-type
macrocycles. In preliminary work, it has been found that a [3 +
3] cyclization product may be isolated as a side product in the
reaction used to prepare 1. X-ray diffraction analysis of this calix-
[9]phyrin 5 reveals the same deep cavity structure as present in
1 (Figure 4). Further studies of this new product are in progress.
For solution-phase studies carried out in acetone, full conver-
sion to the diprotonated form, [1‚2H]2+, was effected by the
addition of 90 molar equiv of H2SO4‚30% SO3 to ca. 9.3 × 10-3
mM solutions of 1. Upon this addition, the intensity of the
absorption band at 449 nm is seen to decrease, whereas that at
499 nm is seen to increase. The solutions also change color from
yellow to pink. Significant shifts in the UV-visible absorbance
spectrum were also seen upon the addition of tetrabutylammonium
salts of chloride, bromide, and iodide to these latter pink solutions.
Under the conditions of this experiment, full saturation (as
determined from a lack of subsequent spectral response) was
observed in the presence of ca. 13, 6, and 60 molar equiv of these
three anions, respectively (Figure 3). While such findings are
consistent with [1‚2H]2+ acting as a protonated “molecular box”
and binding bromide anion with the greatest affinity, only in the
case of iodide anion was a clean fit to a 1:1 binding equilibrium
observed, as judged from Job plots and Benesi-Hildebrand
analysis.11 From the latter, an equilibrium constant of 25 500 (
900 was calculated, corresponding to either direct binding of I-
by [1‚2H]2+ or displacement of hydrogen sulfate from [1‚2H]2+
‚
2HSO4 or [1‚2H]2+‚HSO4
.
-
-
Figure 4. Ortep10 view of 5 showing the heteroatom labeling scheme.
Control experiments involving the addition of Bu4NHSO4 to
solutions of [1‚2H]2+, formed by the addition of 90 molar equiv
Acknowledgment. We thank support from NSF and NIH (grants
CHE9725399 and GM58907 to J.L.S.)
(9) Sessler, J. L.; Gebauer, A.; Weghorn, S. J. In The Porphyrin Handbook;
Kadish, K., Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego,
1999; Vol. 2, p 55.
Supporting Information Available: Crystallographic data, synthetic
experimental for 1, 2, 3, and 5, and binding data for 1 (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
(10) Thermal ellipsoids are scaled to the 40% probability level.
(11) While clean isosbestic behavior was observed through the addition of
13 and 1 molar equiv of anion in the case of chloride and bromide, respectively,
deviations from such behavior, reflecting higher order receptor-to-anion binding
stoichiometries or competition from hydrogen sulfate anions in the formation
of, for example, [1‚2H]2+‚2X- complexes, is observed at higher anion-to-
receptor ratios. Even in the case of titrations of [1‚2H]2+‚2HSO4- with iodide,
deviations from isosbestic behavior are seen at higher anion-to-receptor ratios.
JA005842C
(12) In calculating this value, the effects of possible sulfuric acid ionization
-
were ignored. The 2 molar equiv of HSO4 generated by protonation of 1
were, however, accounted for. See Supporting Information.