p-(1H-phenanthro[9,10-d]imidazol-2-yl)-substituted calix[4]arene, a deep cavity for guest inclusion

Article abstract of DOI:10.1021/ol036287x

The reaction of tetra-p-formyltetra-O-propylcalix[4]arene with phenanthrenequinone in the presence of NH₄OAc affords compound 2, a new class of calixarene with an expanded aromatic cavity, that could be stabilized by hydrogen-bonded bridges and

Full text of DOI:10.1021/ol036287x

ORGANIC
LETTERS
2
004
Vol. 6, No. 7
091-1094
p-(1H-Phenanthro[9,10-d]imidazol-2-yl)-
Substituted Calix[4]arene, a Deep Cavity
for Guest Inclusion
1
†
‡
†
,‡
Enrique Botana, Kalle N a1 ttinen, Pilar Prados, Kari Rissanen,* and
,†,§
Javier de Mendoza*
UniVersidad Aut o´ noma de Madrid, Departamento de Qu ´ı mica Org a´ nica, Cantoblanco,
8049-Madrid, Spain, UniVersity of JyV a¨ skyl a¨ , NanoScience Center, Department of
2
Chemistry, P.O. Box 35, 40014 JYU, Finland, and Institute of Chemical Research of
Catalonia (ICIQ), AVgda. Pa ¨ı sos Catalans s/n, 43007-Tarragona, Spain
jmendoza@iciq.es; kari.rissanen@jyu.fi
Received November 24, 2003
ABSTRACT
4
The reaction of tetra-p-formyltetra-O-propylcalix[4]arene with phenanthrenequinone in the presence of NH OAc affords compound 2, a new
class of calixarene with an expanded aromatic cavity, that could be stabilized by hydrogen-bonded bridges and/or ion pairing, thus preventing
collapse into fully stacked pinched cone conformations as depicted. Two partially protonated calixarenes interdigitate in the solid state to give
rise to a self-assembled face-to-face dimer, stabilized by π−π stacking interactions.
Calixarenes are useful building blocks for the selective
recognition of cations, anions, and neutral molecules. In
calix[4]arenes, the relatively small cavity of the macrocycle
restrains its role to be a platform where the binding groups
are attached and oriented for recognition, which usually takes
place outside the cavity. Although sizable holes may arise
from the larger, less accessible, and more flexible calix[n]-
arenes (n ) 5, 6, 8), the increased flexibility results in poor
1
2
preorganization and frequent collapse.
†
Universidad Aut o´ noma de Madrid.
University of Jyv a¨ skyl a¨ .
Institute of Chemical Research of Catalonia.
‡
The calix[4]arene platform, easily fixed into a cone
conformation by O-alkylation of the phenolic groups with
groups larger than ethyl, could be expanded and deepened
by attachment of further aromatic planar surfaces at the para
§
(1) (a) Gutsche, C. D. Calixarenes; The Royal Society of Chemistry:
Cambridge, 1989. (b) B o¨ hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34,
7
13. (c) Gutsche, C. D. Calixarenes ReVisited; The Royal Society of
Chemistry: Cambridge, 1998. (d) Calixarenes in Action; Mandolini, L.,
Ungaro, R., Eds.; Imperial College Press: London, 2000; and references
therein.
(2) Consoli, G. M.; Cunsolo, F.; Geraci, C.; Gavuzzo, E.; Neri, P. Org.
Lett. 2002, 4, 2649-2652.
1
0.1021/ol036287x CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/02/2004

9
positions of the phenol rings. However, extended surfaces
such as styrene, 1-naphthyl, or carbazol-9-yl attached at two
opposite rings give rise to “pinched” cone structures stabi-
lized by π-π interactions, so no permanent cavities are
presence of an excess ammonium acetate. Model compound
5
derivative 6, used as a control.
1
0
was prepared similarly and, together with its N-methyl
The structure of 2 was mainly established by MALDI-
TOF (m/z ) 1458.6 [M + H] ) and ESI (m/z ) 1458.7 [M
H] , 729.6 [M + 2H] ) mass spectrometries, as well as
by H and C NMR and elemental analysis.
3
available for guest encapsulation. Introduction of four
+
substituents instead of two does not contribute either to
prevent collapse. For instance, attachment of four 1,8-
naphthalene imides to the wider rim of a calix[4]arene yields
the deep structure 1, which is again collapsed into a pinched
+
2+
+
1
13
The compound was almost insoluble in most organic,
nonprotic solvents, but addition of ca. 25% methanol or protic
acids, such as trifluoroacetic acid (TFA) or HCl, to a
suspension in chloroform resulted in clean solutions. Broad
signals were observed in the H NMR spectrum (CDCl
4
cone conformation. Moreover, X-ray analysis reveals that
the outer aromatic imides are almost perpendicular to the
respective phenol rings, whereas the inner ones are twisted
1
3
/
60° to reach an optimal stacking and to minimize the
2 2
MeOD or CD Cl /MeOD) (Figure 1a), even at low temper-
repulsions between the adjacent carbonyl groups. Conse-
quently, no encapsulation was reported.
We describe herein calix[4]arene 2, a deep cone-shaped
macrocycle bearing four coplanarly oriented 1H-phenanthro-
[9,10-d]imidazol-2-yl groups. The location of imidazole N
and NH heteroatoms within the ensemble opens the pos-
sibility to preventing full collapse or stabilize the shape into
a more preorganized conical conformation by linking the
large planar aromatic surfaces through hydrogen-bonded ion
5
,6
pairs. In addition, the phenanthroimidazole moiety is a
stable chromophore endowed with high extinction coef-
7
ficients and fluorophoric properties.
Figure 1. 1H NMR spectra of 2: (a) in CDCl
DMSO-d , (c) in CDCl /CF CO H. The highest peaks marked with
a double line are solvent peaks.
/MeOD, (b) in
Calixarene 2 was readily obtained in 65% yield by reaction
of tetrakis-p-formylcalix[4]arene (4) with 8 equiv of 9,10-
phenanthrenequinone (3) in refluxing acetic acid in the
3
8
6
3
3
2
(
3) (a) Larsen, M.; Krebs, F. C.; Jorgensen, M.; Harrit, N. J. Org. Chem.
998, 63, 4420-4424. (b) Larsen, M.; Krebs, F. C.; Jorgensen, M.; Harrit,
N. J. Chem. Soc., Perkin Trans. 2 1999, 1749-1757.
4) Vysotsky, M. O.; B o¨ hmer, V.; W u¨ rthner, F.; You, C.; Rissanen, K.
Org. Lett. 2002, 4, 2901-2904.
1
ature (188 K), probably due to a slow equilibrium between
several conformers.
11
(
On the contrary, the spectrum in DMSO-d
resolved and could be fully assigned through a ROESY
experiment (Figures 1b and 2). The ArCH Ar protons appear
6
was well
(
5) For an example of stabilization of a Vase C4V conformation by
hydrogen-bonded water bridges in a resorcinarene-benzimidazole ensemble,
see: Far, A. R.; Shivanyuk, A.; Rebek, J., Jr. J. Am. Chem. Soc. 2002,
2
1
24, 2854-2855.
6) For examples of solvent-sealed hydrogen bonded molecular capsules,
as an AX system (δ ) 4.71 and 3.69 ppm), typical for a C4V
conical structure or for pinched conformers in rapid equi-
librium.
(
see: (a) Rose, K. N.; Barbour, L. J.; Orr, G. W.; Atwood, J. L. Chem.
Commun. 1998, 407-408. (b) Murayama, K.; Aoki, K. Chem. Commun.
1
998, 607-608. (c) Atwood, J. L. Nature 1999, 389, 469-472. (d)
Shivanyuk, A.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 7662-
7
665. (e) Mansikkam a¨ ki, H.; Nissinen, M.; Rissanen, K. Chem. Commun.
002, 1902-1903.
(9) (a) Steck, E. A.; Day, A. R. J. Am. Chem. Soc. 1943, 65, 452-456.
(b) McCoy, G.; Day, A. R. J. Am. Chem. Soc. 1943, 65, 2159-2162. (c)
Lantos, I. J. Org. Chem. 1975, 40, 1641-1642. (d) Sakaino, Y.; Kakisawa,
H.; Kusumi, T. J. Chem. Soc., Perkin Trans. 1 1975, 2361-2364.
(10) Sakaino, Y.; Kakisawa, H.; Kusumi, T. J. Heterocycl. Chem. 1975,
12, 953-956.
(11) A similar behavior has been described for calix[4]arene 1 endowed
with four naphthalene imides, although a well-resolved spectrum, accounting
for a stable pinched cone, was observed at -58°C (see ref 4).
2
(
7) (a) Krebs, F. C.; Lindvold, L. R.; Jorgensen, M.; Harrit, N.
Tetrahedron Lett. 2001, 42, 6753-6757. (b) Krebs, F. C.; Jorgensen, M. J.
Org. Chem. 2001, 66, 6169-6173. (c) Krebs, F. C.; Spanggaard, H. J. Org.
Chem. 2002, 67, 7185-7192 and references therein. (d) Krebs, F. C.
Tetrahedron Lett. 2003, 44, 6343-6646.
(
8) Dondoni, A.; Marra, A.; Scherrmann, M.-C.; Casnati, A.; Sansone,
F.; Ungaro, R. Chem. Eur. J. 1997, 3, 1774-1782.
1092
Org. Lett., Vol. 6, No. 7, 2004

Remarkably, a slow annular tautomerism of the imidazole
rings was observed, as evidenced by the split signals for H
and H or for H and H (see the Supporting Information).
a
h
d
e
The structure becomes symmetric at 413 K, and coalescence
was found at 318 K (Figure 3). In contrast, control compound
5
displays a rapid tautomeric equilibrium at room temper-
ature, as expected. Both the slow in the tautomeric equilib-
rium and the well-resolved structure in solution could be
explained by the presence of bridges between the heterocyclic
subunits, established through a complement of hydrogen
bond donors and acceptors, such as water or DMSO
molecules, as depicted in Figure 2.
Figure 3. 1H NMR spectrum of 2 (aromatic region) in DMSO-d
.
6
6
Figure 2. Proposed structure for 2 in DMSO-d . Arrows indicate
the main NOE cross-peaks found in the ROESY spectrum.
Oxoanions could also act as hydrogen acceptor bridges
between the subunits. Indeed, a well-resolved spectrum in
CDCl /TFA compatible with a C -symmetric cone conforma-
3 4
tion was obtained at room temperature (Figure 1c). Interest-
ingly, the singlet at 13.93 ppm (imidazolium NH) does not
average with the TFA signal. However, splitting of signals
is observed at 233 K, in agreement with the presence of two
equivalent distorted or pinched cones in equilibrium (see the
Supporting Information).
3
In CDCl /HCl, the spectrum of 2 was too broad to be
analyzed by NMR. Thus, protonation of the imidazole rings
is not the only requirement to obtain well-resolved spectra.
Likely, TFA establishes four hydrogen-bonded, ion-paired
bridges that prevent rotation of the phenanthroimidazole
moieties on top of the calixarene platform (see in the Abstract
graphic).
Attempts to obtain crystals from a dichloromethane/TFA
mixture failed, but suitable crystals for X-ray analysis were
grown by slow evaporation of a 1:4 ratio of 2 and TFA in a
solution of CH Cl
2 2
/MeOH (3:1).12 The structure 7 contains
Figure 4. X-ray structure 7 with one calix[4]arene 2, three TFA,
and three MeOH bridging molecules: (a) side view, (b) top view.
Hydrogens are omitted for clarity.
molecule 2 with three of its phenanthroimidazole groups
protonated by three TFA molecules, respectively (Figure 4).
Two out of the three TFA molecules bridge the neighbor-
ing imidazole groups through strong hydrogen bonds (lengths
from 1.679 to 1.821 Å). The third TFA is hydrogen bonded
to one imidazole hydrogen and also involved in a pattern of
hydrogen bonds including two methanol molecules and a
Org. Lett., Vol. 6, No. 7, 2004
1093

solution with suitable guests. Thus, addition of N-methyl
model 6 to a solution of 2 in CDCl /TFA resulted in a 0.2-
.4 ppm upfield shift of the H NMR signals for the aromatic
CH protons, which are likely inside the cavity, while the
OCH signal, at the outside, remained essentially unchanged.
3
1
0
3
The N-methyl signal of 6 was hardly seen at room temper-
ature, due to extensive broadening, but showed a remarkable
upfield shift (ca. 1.2 ppm) at 233 K, accounting for its
inclusion deeply into the cavity. Upon cooling, the calixarene
conformation equilibria frozen and signals for both the
complex and free host and guest components are neatly
resolved at 233 K in a 35:65 ratio. Moreover, the signals
corresponding to the NH protons of the host were split into
four signals in the complex, accounting for the loss of
symmetry induced by the guest upon encapsulation (see the
Supporting Information).
In summary, we have described a new deep calixarene
whose cavity can be stabilized by hydrogen-bonded bridges
and/or ion pairing, suitable for encapsulation of sizable
guests. The presence of imidazole subunits opens the possi-
bility of establishing a more robust array of covalent bridges
by alkylation and quaternization with suitable difunctional-
ized spacers. In resorcinarenes (the calix[4]arene resorcinol
analogues), the flexible structure can be rigidified into the
13
so-called cavitands by short spacers. A similar strategy with
phenanthroimidazole calix[n]arenes such as 2, would lead
to polycationic permanent well preorganized cavities useful
for molecular recognition, catalysis or molecular materials.
Our results in these directions will be reported on due time.
Acknowledgment. We are grateful to “Ministerio de
Ciencia y Tecnolog ´ı a” of Spain for financial support (Grant
No. BQU2002-03536).
Figure 5. Packing of two interleaved calixarenes in the crystal
showing the offset face-to-face π-π interactions: (a) ball-and-stick
representation; (b) CPK model.
Supporting Information Available: Experimental pro-
cedures for the synthesis of 2-6, NMR spectra for com-
pounds 2, 5, 6, and complex 2•6, as well as crystal structure
data for 7. This material is available free of charge via the
Internet at http://pubs.acs.org.
protonated imidazole. The TFA creates a bridge between the
imidazole groups together with the two methanol molecules.
The fourth bridge involves a methanol molecule. The
hydrogen bonding was clearly observable despite the rota-
tional disorder of the trifluoromethyl groups of the TFA
molecules.
OL036287X
The bridging results in a distorted, pinched cone confor-
mation which is further stabilized by dimerization with the
paired phenanthroimidazole arms gripping one another by
offset face-to-face π-π interactions (Figure 5). The winged
phenanthroimidazole arms participate in the dimerization by
accepting CH-π hydrogen bonds. The CH-π (centroid)
distance is 2.913(2) Å and the π-π interaction lengths range
from 3.496(1) to 3.797(1) Å.
(
12) Crystallographic measurement at 123.0(1) K using an Enraf Nonius
Kappa-CCD diffractometer, Mo KR radiation. Structure solution by direct
methods, full matrix least-squares refinement on F2, no absorption correc-
tion: C111H83O13N8Cl4F9, M 2049.65, crystal size 0.40 × 0.30 × 0.15 mm,
triclinic, space group P-1 (No. 2), a ) 14.7972(2) Å, b ) 16.9446(3) Å, c
) 22.5701(3) Å, R ) 97.406(1)°, â ) 106.599(1)°, γ ) 109.447(1)°, V )
3
3
-1
4
1
4
964.2(1) Å , Z ) 2, Dc ) 1.374 g/cm , ´ı ) 0.205 mm , 32705 reflections,
6844 independent, Rint ) 0.0409, R1 ) 0.1021, wR2 ) 0.2687 for I >
σ(I), 1298 parameters, S ) 1.064.
(13) (a) Cram, D. J.; Choi, H.-J.; Bryant, J. A.; Knobler, C. B. J. Am.
Chem. Soc. 1992, 114, 7748-7765. (b) Cram, D. J. In Container Molecules
and their Guests; Stoddart, F., Ed.; The Royal Society of Chemistry:
London, 1994.
In good agreement with those results in the solid state,
compound 2, in the presence of TFA, interacts also in
1094
Org. Lett., Vol. 6, No. 7, 2004