A new cryptand: Synthesis and complexation with paraquat

Article abstract of DOI:10.1021/ol990780k

(matrix presented) Inspired by folded, nonpseudorotaxane complexes of bis(m-phenylene)-32-crown-10 systems, we synthesized a new bicyclic crown ether containing two 1,3,5-phenylene units linked by three tetra(ethyleneoxy) units. The new cryptand forms a "

Full text of DOI:10.1021/ol990780k

ORGANIC
LETTERS
1999
Vol. 1, No. 7
1001-1004
A New Cryptand: Synthesis and
Complexation with Paraquat
William S. Bryant,‡ Jason W. Jones,‡ Philip E. Mason,‡ Ilia Guzei,†
Arnold L. Rheingold,† Frank R. Fronczek,¥ Devdatt S. Nagvekar,‡ and
,‡
Harry W. Gibson*
Department of Chemistry, Virginia Polytechnic Institute & State UniVersity,
Blacksburg, Virginia 24061, Department of Chemistry, UniVersity of Delaware,
Newark, Delaware 19716, and Department of Chemistry, Louisiana State UniVersity,
Baton Rouge, Louisiana 70803
hwgibson@Vt.edu
Received July 2, 1999
ABSTRACT
Inspired by folded, nonpseudorotaxane complexes of bis(m-phenylene)-32-crown-10 systems, we synthesized a new bicyclic crown ether
containing two 1,3,5-phenylene units linked by three tetra(ethyleneoxy) units. The new cryptand forms a “pseudorotaxane-like” inclusion
complex with N,N′-dimethyl-4,4′-bipyridinium bis(hexafluorophosphate) with association constant Ka ) 6.1 × 104 M-1, 100-fold greater than
that of an analogous simple crown ether.
Crown ethers were first reported in 1967,1 nearly simulta-
neously2 with the first rotaxanes (compounds consisting of
cyclic molecules threaded by linear molecules with no
covalent bonds between them, Figure 1). Not long thereafter,
bicyclic compounds with cavities capable of inclusion of ions
and small molecules were reported.3 Such cryptands, defined
as “bicyclic ligands”,4 have been demonstrated to be valuable
hosts for a variety of guests; indeed, association constants
can be 103-104 times higher than those of the analogous
macrocycles,4-6 attributable to the preorganization of their
structures.7
Crown ethers have played a significant role in the
emerging field of supramolecular chemistry. Interestingly,
one of the most significant advances in the field resulted
‡ Virginia Polytechnic Institute and State University.
† University of Delaware.
¥ Louisiana State University.
(1) (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495. Pedersen, C.
J. J. Am. Chem. Soc. 1967, 89, 7017. Pedersen, C. J. Angew. Chem., Int.
Ed. Engl. 1988, 27, 1021.
(2) Schill, G.; Zo¨llenkopf, H. Nachr. Chem. Technol. 1967, 79, 149.
Harrison, I. T.; Harrison, S. J. Am. Chem. Soc. 1967, 89, 5723. Schill, G.;
Zo¨llenkopf, H. Ann. Chem. 1969, 721, 53.
(3) Simmons, H. E.; Park, C. H. J. Am. Chem. Soc. 1968, 90, 2428.
2429; 2431. Dietrich, B.; Lehn, J.-M.; Sauvage, J.-P. Tetrahedron Lett. 1969,
2885.
(4) Dietrich, B. In ComprehensiVe Supramolecular Chemistry; Atwood,
J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F., Series Eds.; Pergamon
Press: New York, 1996; Vol. 1, Gokel, G., Vol. Ed., Chapter 4, pp 153-
211.
Figure 1. Schematic representations of a rotaxane (left) and a
pseudorotaxane (right). Cyclic molecular unit in red, linear mo-
lecular unit in blue, and blocking group in gray.
10.1021/ol990780k CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/15/1999

from the quest for effective hosts for complexation of
of the complex 1a:2b, which, as shown in Figure 2, also
“paraquats”, N,N′-dialkyl-4,4′-bipyridinium salts (1), by
proved to be of the same folded, exo type and not the
Stoddart et al. in the early 1980s.8,9a It was discovered that
bisarylene crown ethers in the size range of 32-34 atoms,
in particular, form pseudorotaxanes (mechanically threaded
structures without bulky end groups to provide thermo-
dynamic stability against dethreading, Figure 1) with paraquats
with association constants on the order of 102-103 M-1,8,9
and from this genesis, a variety of pseudorotaxanes, rotaxanes
(Figure 1), catenanes, and polyrotaxanes have been synthe-
sized.10
During the characterization of bis(1,3-phenylene)-32-
crown-10 systems (2), folded, “exo” complexes have been
observed by X-ray crystallography. For example, we recently
Figure 2. Solid-state structure of 1a:2b as determined by X-ray
crystallography14a,b [disordered solvent molecules (water and
acetone, which share a site) and counterions omitted for clarity,
except for a fluorine atom of one PF6, represented by the gray
circle)]. Both positions of the disordered oxygen atom of the
hydroxymethyl group, denoted by **, are shown treated as half-
populated. H-bond distances in Å: a ) 2.44, b ) 2.83, c ) 2.34,
d ) 2.42, e ) 2.72. H-bond angles (C-H- -O, C-H- -F, or
O-H- -O) in degrees: a ) 144, b ) 130, c ) 168, d ) 144, e )
156.
reported11 a “cradled barbell” crystal structure and not the
expected pseudorotaxane structure from the parent system
2a9a,12 with N,N′-dibenzyl(m-xylylene)diammonium bis-
(hexafluorophosphate), although the parent macrocycle is not
folded in its crystal.9a Examination of the complexation of
the diol 2b13 with paraquat 1a led to the isolation of crystals
expected pseudorotaxane structure, even though its FAB
mass spectrum displays a peak (m/z 927.3) corresponding
to (1a:2b-PF6)+ and in its crystal structure 2b itself does
not exhibit this folded structure. Note that in complex 1a:
2b the electron rich aromatic rings of the host are nicely
aligned vertically with and parallel to the electron poor
aromatic rings of the guest species; the bipyridinium twist
angle is 11.4° from coplanar and the crown aromatic rings
are tilted 6.9° with repect to each other. The centroid-
centroid distance of the aromatic rings of the crown ether is
7.39 Å. There are three H-bonds of two of the acidic
R-protons of the paraquat unit with the ether oxygen atoms
(5) Parsons, D. G. J. Chem. Soc., Perkin Trans. 1 1978, 451.
(6) Lehn, J.-M. Supramolecular Chemistry; VCH Publishers: New York,
1995.
(7) The concept of preorganization can logically be traced to the “lock
and key” idea of Fischer (Chem. Ber. 1894, 27, 2985). The enhanced
effectiveness of macrocyclic hosts (coronands) over linear analogues
(podands) (ref 1), the macrocyclic effect, suggested further improvements
with cryptands. Further development included significant contributions from
Cram (Cram, D. J.; Cram, J. M. Container Molecules and Their Guests;
Royal Society of Chemistry: Cambridge, UK, 1994) and Lehn (ref 6). For
a very instructive review of these concepts, see: Inoue, Y.; Wada, T. AdV.
Supramol. Chem. 1997, 4, 55.
-
of the host. Uniquely, the counterion, PF6 , also participates
in stabilization of the complex through H-bonds to two of
the protons of the paraquat guest unit; though this effect has
been observed in dialkylammonium ion-crown ether com-
plexes,15 to our knowledge it has not been previously seen
in paraquat-based pseudorotaxanes.
(8) Stoddart, F. Chem. Br. 1991, 714.
(9) (a) Allwood, B. L.; Spencer, N.; Shahriari-Zavareh, H.; Stoddart, J.
F.; Williams, D. J. J. Chem. Soc., Chem. Commun. 1987, 1058. (b) Asakawa,
M.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Belohradsky, M.; Gandolfi,
M. T.; Kocian, O.; Prodi, L.; Raymo, F. M.; Stoddart, J. F.; Venturi, M. J.
Am. Chem. Soc. 1997, 119, 302. (c) Asakawa, M.; Ashton, P. R.; Boyd, S.
E.; Brown, C. L.; Gillard, R. E.; Kocian, O.; Raymo, F. M.; Stoddart, J. F.;
Tolley, M. S.; White, A. J. P.; Williams, D. J. J. Org. Chem. 1997, 62, 26
and references therein.
(10) Reviews: Mahan, E.; Gibson, H. W., In Cyclic Polymers, 2nd ed.;
Semlyen, A. J., Ed.; Thomson Science and Professional: London, UK, in
press. Raymo, F. M.; Stoddart, J. F. Chem. ReV. 1999, 99, 9, ASAP web
posting June 11, 1999. Harada, A. Acta Polym. 1998, 49, 3. Gibson, H. W.
In Large Ring Molecules; Semlyen, J. A., Ed.; John Wiley & Sons: New
York, 1996; Chapter 6, pp 191-262. Philp, D.; Stoddart, J. F. Angew. Chem.,
Int. Ed. Engl. 1996, 1155.
(14) (a) Crystals of 1a:2b were grown by diffusion of hexane into an
equimolar acetone solution of the components. X-ray diffraction was carried
out on an Enraf-Nonius CAD4 diffractometer equipped with Cu K radiation
(λ ) 1.541 84 Å) and a graphite monochromator. Data were collected to θ
) 75°. Crystal data: C30H44O12:[C12H14N2](PF6)2:1/2(C3H6O):1/2(H2O), FW
1110.9, monoclinic space group P21/c, a ) 10.7679(8), b ) 15.677(1),
and c ) 2.453(4) Å, â ) 93.196(8)°, V ) 5469(1) Å3, Z ) 4, Dc ) 1.349
g cm-3, T ) 297 K, µ ) 16.0 cm-1. Convergence was achieved with R )
0.118, Rw ) 0.143, and maximum residual density 0.72 e Å-3 for 5502
data having I > 1σ(I) (of 11712 unique data). (b) The structures were solved
by direct methods using SIR (Burla, M. C.; Camalli, M.; Cascarano, G.;
Giacovazzo, C.; Polidori, G.; Spagna R.; Viterbo, D. J. Appl. Crystallogr.
1989, 22, 389) and refined by full-matrix least squares, using the Enraf-
Nonius MolEN programs (Fair, C. K. MolEN, An InteractiVe System for
(11) Bryant, W. S.; Guzei, I. A.; Rheingold, A. L.; Gibson, H. W. Org.
Lett. 1999, 1, 47.
(12) Delaviz, Y.; Gibson, H. W. Polym. Commun. 1991, 32, 103.
(13) Gibson, H. W.; Nagvekar, D. S. Can. J. Chem. 1997, 75, 1375.
1002
Org. Lett., Vol. 1, No. 7, 1999

On the basis of the suggestion implicit in the structure of
1a:2b that closure of a second ring would enhance the
strength of the complexation and the historical success of
cryptands in affording higher association constants and hence
more efficient routes to such supramolecular assemblies, bis-
(1,3,5-phenylene)tri(1,4,7,10,13-pentaoxatridecyl) (3) was
synthesized in one step from bisphenol 2d16 and tetra-
(ethylene glycol) ditosylate in 38% yield using the pseudo-
Figure 3. Partial 1H NMR spectra (400 MHz, acetone-d6, 21 °C)
of (a, bottom) bicyclic crown ether 3 (2.69 mM), (b, middle)
paraquat (1a, 2.69 mM), and (c, top) a solution of both 1a and 3
(2.69 mM each).
high-dilution technique.13 3 was characterized by 1H and 13
C
NMR and MS.17
When 1a and 3 were mixed in acetone, the yellow color
(λmax ) 396 nm) typical of such charge-transfer inclusion
complexes formed immediately. 1H NMR spectroscopy
(Figure 3) indicated that exchange was rapid and complex-
ation was strong on the basis of the significant upfield shifts
of the bipyridinium protons, the aromatic proton, and the
R-OCH2 protons of 3 and the downfield shift of the γ- and
δ-OCH2 protons of 3, qualitatively similar to those observed
for other bisphenylene crown ether-paraquat complexes.8,9
Solutions of 1b and 3 behaved similarly.
A Job plot based on NMR data demonstrated that the
complex was of 1:1 stoichiometry. The NMR data afforded
an estimate of the association constant18,19 for 1a:3, Ka )
6.1 × 104 M-1 at 23.4 °C in acetone-d6, corresponding to
∆G ) -92 kJ/mol, a value which at this point must be
regarded as preliminary in view of the difficulty in measuring
such high association constants accurately by NMR.20 This
is among the highest values reported for crown ether
complexes of paraquats.21 For 1a:2b the NMR data yielded18,19
Ka ) 5.7 × 102 M-1 (∆G ) -53 kJ/mol) under the same
conditions. The 100-fold increase in Ka at 23 °C for the
complex of bicyclic crown ether 3 vs that of simple crown
ether 2b represents nearly a doubling of ∆G. Thus, as
expected, the bicyclic system 3 is a stronger host for
complexation with paraquat. Again 1b interacted with 3 in
an analogous manner and the Ka value was similar.
The 1:1 complex 1a:3 was detected directly by FABMS.
Two relevant peaks were observed: m/z 1057.45 for the
complex after loss of a PF6 counterion and m/z 912.62 for
the complex after loss of a PF6 counterion and a neutral PF6.
This fragmentation pattern has been observed in many
pseudorotaxanes and catenanes derived from paraquat de-
rivatives.8,9
Crystal Structure Analysis; Enraf-Nonius: Delft, The Netherlands, 1990).
Non-hydrogen atoms were treated anisotropically except those of the
disordered solvent molecules. Hydrogen atoms were placed in calculated
positions, except those on the water molecules and the paraquat methyl
groups, which were placed from difference maps. Acetone H atoms were
not located. (c) Crystals of 1a:3 were grown by evaporation of an equimolar
acetone solution of the two components. X-ray diffraction was carried out
on a Siemens P4/CCD diffractometer equipped with Mo KR radiation (λ
) 0.710 73 Å) and a graphite monochromator. Data were collected to θ )
22.5°. Crystal data: C36H54O15:C12H8N2(PF6)2:H2O:C3H6O, FW 1297.09,
triclinic space group P-1, a ) 25.0865 (1), b ) 11.1315 (2), and c ) 23.4900
(2) Å; R ) 90.00, â ) 107.671 (1), γ ) 90.00°; V ) 6250.08 (12) Å3, Z
) 4, Dc ) 1.378 g cm-3, T ) 213(2) K, µ ) 0.173 cm-1. Convergence
was achieved with R ) 0.0825, Rw ) 0.2291, and maximum residual density
0.836 e‚Å-3 for 5130 data having I > 2σ(I).
X-ray diffraction results (Figure 4) confirmed the 1:1
stoichiometry and the structure of the “pseudorotaxane-
(18) The association constants were estimated on the basis of the chemical
shift of proton Ha of the uncomplexed cryptand 3 or crown ether 2b and
the observed signals in the presence of varied amounts of 1a (titration).
(19) Using the iterative Creswell-Allred method: Gong, C.; Balanda,
P. B.; Gibson, H. W. Macromolecules 1998, 31, 5278.
(20) Tsukube, H.; Furuta, H.; Odani, A.; Takeda, Y.; Kudo, Y.; Inoue,
Y.; Liu, Y.; Sakamoto, H.; Kimura, K.. In ComprehensiVe Supramolecular
Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F.,
Series Eds.; Pergamon Press: New York, 1996; Vol. 8, Davies, J. E. D.,
Ripmeester, J. A., Vol. Eds., Chapter 10, pp 425-482.
(15) Fyfe, M. C. T.; Stoddart, J. F. AdV. Supramol. Chem. 1999, 5, 1.
(16) Bisphenol 2d was derived from 5-benzyloxyresorcinol [Nagvekar,
D.; Gibson, H. W. Org. Prep. Proced. Int. 1997, 29, 240] via 2c using the
methodology reported for other derivatives of bis(m-phenylene)-32-crown-
10 (ref 13). Details are given in the Supporting Information.
(21) Nolte and co-workers reported that a bicyclic molecule containing
two tetra(ethyleneoxy) bridges and a diphenylglycouril bridging moiety
complexes 1a with Ka ) 2.0 × 104 M-1 (in acetone at room temperature:
Schenning, A. P. H. J.; deBruin, B.; Rowan, A. E.; Kooijman, H.; Spek, A.
L. Angew. Chem., Int. Ed. Engl. 1995, 34, 2132), i.e., 1/3 of the value we
observe for 1a:3. Rowan et al. (Rowan, A. E.; Aarts, P. P. M.; Koutstaal,
K. W. M. Chem. Commun. 1998, 611) recently reported that a “porphyrin
capped molecular clip” having crown ether and diphenylglycouril compo-
nents formed a “pseudorotaxane-like” complex with 1a with Ka ) 6.0 ×
105 M-1, in a less polar solvent system (1:1 MeCN-CHCl3, room
temperture). It should be noted that this host is also a cryptand containing
a very strong electron donor, the porphyrin unit.
(17) 1H NMR (CDCl3) δ ) 3.69 (m-, γ-, δ-OCH2, 24H), 3.81 (t, J )
4.6 Hz, â-OCH2, 12H), 3.93 (t, J ) 4.6 Hz, R-OCH2, 12H) and 6.00 (s,
6H). 13C NMR (CDCl3) δ ) 67.47, 69.66, 70.64, 70.94, 94.20 and 160.41.
FABMS (3-nitrobenzyl alcohol, NBA) m/z (rel intensity): 749.1 [(M +
Na)+, 100%], 727.2 [(M + H)+ 32%], and 705.3 [(M + Na)+ - C2H4O,
15%]. High-resolution FABMS (3-NBA): m/z 749.3373 (M + Na)+ [calcd
for C36H54O15Na, 749.3373].
Org. Lett., Vol. 1, No. 7, 1999
1003

are very similar to those features in the simple crown
complex 1a:2b (Figure 2). As in 1a:2b (Figure 2) there are
four H-bonds emanating from the paraquat unit. Two of the
R-protons of 1a are involved in H-bonding with ether oxygen
atoms, whereas in previously reported bisphenylene pseudo-
rotaxane systems all four R-protons are involved in such
H-bonding.8,9 Moreover, in 1a:3 two adjacent â-protons are
H-bonded to a water molecule, which in turn is H-bonded
to two ethereal oxygen atoms. This is believed to be the first
reported inclusion complex with demonstrated H-bonding
of the â-protons of paraquat. As expected for a π-stacking
interaction, the aromatic rings of the cryptand in 1a:3 are
nearly (9.8°) parallel, with a 6.94 Å centroid-centroid
separation; the paraquat moiety, whose rings are twisted 5.8°
out of planarity, lies nearly parallel to and nearly sym-
metrically between the two arylene units of 3. In comparison
to the structure of 1a:2b (Figure 2), the aromatic rings of
the cryptand in 1a:3 are closer to the paraquat unit and to
each other.
Figure 4. Solid-state structure of 1a:3 as determined by X-ray
crystallography14b,c (solvent molecules and counterions omitted for
clarity except as noted). H-bond distances in Å: a ) 2.63, b )
2.34, c ) 2.29, d ) 2.05, e ) 2.07, f ) 2.75. H-bond angles
(C-H- -O or O-H- -O) in degrees: a ) 149, b ) 179, c ) 175,
d ) 160, e ) 165, f ) 152.
Thus, we have demonstrated the enhanced ability (relative
to simple macrocycle 2b) of a readily prepared bicyclic
crown ether (3) to form paraquat-based “pseudorotaxanes-
like” 22 inclusion complexes. Current efforts are focused on
extension of the use of such preorganized host structures to
other systems.
like” 22 inclusion complex of 1a:3. Note that the position
and orientation of the paraquat guest unit in this complex
Acknowledgment. We acknowledge financial support of
this research by the National Science Foundation through
Individual Investigator Award CHE-9521738. Mass spectral
data were obtained from the Washington University Mass
Spectrometry Resource, an NIH Research Resource (Grant
P41RR0954).
(22) This term was used by Stoddart et al. to describe analogous inclusion
complexes of 1a and 1b with bis(p-phenylene)-34-crown-10 (BMP34C10)
(Ashton, P. R.; Philp, D.; Reddington, M. V.; Slawin, A. M. Z.; Spencer,
N.; Stoddart, J. F.; Williams, D. J. J. Chem. Soc., Chem. Commun. 1991,
1680). A referee suggested that 1a:3 is not a “true” pseudorotaxane because
1a is not long enough to extend outside the cavity of 3. This is a somewhat
subjective point since the methyl groups of 1a protrude only slightly from
the cavity. In the case of 1b:3, however, 1b is long enough to do so, as
clearly shown by single-crystal X-ray analyses with BMP34C10 in our own
work (Shen, Y. X.; Engen, P. T.; Gibson, H. W.; Merola, J. S. Abstracts of
Papers, 201st National Meeting of the American Chemical Society, Atlanta,
GA, April 1991; American Chemical Society: Washington, DC, 1991:
ORGN 325. Shen, Y. X.; Engen, P. T.; Berg, M. A. G.; Merola, J. S.;
Gibson, H. W. Macromolecules 1992, 25, 2786) and that of Stoddart (above
reference). We thus anticipate that 1b:3 is a “true” pseudorotaxane.
Supporting Information Available: Synthetic procedures
for 2c, 2d, and 3. Crystal data, structure refinement details,
and SHELXTL files (.res) for 1a:2b and 1a:3. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL990780K
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Org. Lett., Vol. 1, No. 7, 1999