A Unique Spherical Molecular Host with D2d Symmetry. A Novel Intramolecular Kinetic Equilibrium in Metal Ion Complexation between Two Crown Ethers

Article abstract of DOI:10.1021/ol026780t

(Matrix Presented) A spherical host with D_2d symmetry consisting of a tetrathia[3.3.3.3]paracyclophane and two 18-crown-6 moieties was synthesized. Its crystal structure shows a central cavity with a diameter of 1.96 A and a depth of 6.75 A. A

Full text of DOI:10.1021/ol026780t

ORGANIC
LETTERS
2002
Vol. 4, No. 22
3911-3914
A Unique Spherical Molecular Host with
D Symmetry. A Novel Intramolecular
2d
Kinetic Equilibrium in Metal Ion
Complexation between Two Crown
Ethers
,†
Jianwei Xu,†,‡ Yee-Hing Lai,* and Chaobin He‡
Department of Chemistry, National UniVersity of Singapore, 3 Science DriVe 3,
Republic of Singapore 117543, and Institute of Materials Research and Engineering,
3 Research Link, Republic of Singapore 117602
chmlaiyh@nus.edu.sg
Received August 24, 2002
ABSTRACT
A spherical host with D2d symmetry consisting of a tetrathia[3.3.3.3]paracyclophane and two 18-crown-6 moieties was synthesized. Its crystal
structure shows a central cavity with a diameter of 1.96 Å and a depth of 6.75 Å. A Na+ ion could rest in the cavity center but prefers core
binding to external binding in one of the crown units. An intramolecular kinetic equilibrium was reached with the Na+ ion switching between
the two crown units with an energy barrier of 14.1 ± 3 kcal/mol.
The closed-surface carcerands, which can incarcerate simple
organic molecules or inorganic ions, have been extensively
studied1-4 and well documented.5,6 Generally, a guest
imprisoned by a carcerand suffers from poor communication
with external species, and the confined guest cannot escape
from the host unless bond breaking is involved.6 A hemi-
carcerand7 having a size-restricting portal on the surface not
only holds a guest but also communicates with external ones.
However, it still retains the guests firmly in its cavity. If the
two cofacial, closed-surface components are crown ethers
† National University of Singapore.
‡ Institute of Materials Research and Engineering.
(1) (a) Cram, D. J.; Karbach, S.; Kim, Y. H.; Baczynskyj, L.; Kalleymeyn,
G. W. J. Am. Chem. Soc. 1985, 107, 2575. (b) Cram, D. J.; Karbach, S.;
Kim, Y. H.; Baczynskyj, L.; Marti, K.; Sampson, R. M.; Kalleymeyn, G.
W. J. Am. Chem. Soc. 1988, 110, 2554.
(2) (a) Bryant, J. A.; Blanda, M. T.; Vincenti, M.; Cram, D. J. J. Chem.
Soc. Chem. Commun. 1990, 1403. (b) Bryant, J. A.; Blanda, M. T.; Vincenti,
M.; Cram, D. J. J. Am. Chem. Soc. 1991, 113, 2167. (c) Sherman, J. C.;
Cram, D. J. J. Am. Chem. Soc. 1989, 111, 4527. (d) Sherman, J. C.; Knobler,
C. B.; Cram, D. J. J. Am. Chem. Soc. 1991, 113, 2194.
(6) Cram, D. J.; Cram, J. M. Container Molecules and Their Guests;
Royal Society of Chemistry: Cambridge, 1994.
(7) (a) Cram, D. J.; Tanner, M. E.; Knobler, C. B. J. Am. Chem. Soc.
1991, 113, 7717. (b) Robbins, T. A.; Knobler, C. B.; Bellew, D. R.; Cram,
D. J. J. Am. Chem. Soc. 1994, 116, 111. (c) Von dem Bussche-Hu¨nnefeld,
C.; Buehring, D.; Knobler, C. B.; Cram, D. J. Chem. Soc. Chem. Commun.
1995, 1085. (d) Lutzen, A.; Hass, O.; Bruhn, T. Tetrahedron Lett. 2002,
43, 1807. (e) Warmuth, R.; Yoon, J. Acc. Chem. Res. 2001, 34, 95. (f) Ro,
S.; Rowan, S. J.; Pease, A. R.; Cram, D. J.; Stoddart, J. F. Org. Lett. 2000,
2, 2411. (g) Warmuth, R. J. Am. Chem. Soc. 2001, 123, 6955. (h) Yoon, J.;
Cram, D. J. J. Am. Chem. Soc. 1997, 119, 11796. (i) Cram, D. J.; Blanda,
M. T.; Paek, K.; Knobler, C. B. J. Am. Chem. Soc. 1992, 114, 7765. (j)
Yoon, J. Cram, D. J. J. Chem. Soc., Chem. Commun. 1997, 1505.
(3) Cram, D. J. Nature 1992, 356, 29.
(4) Jasat, A.; Sherman, J. C. Chem. ReV. 1999, 99, 931.
(5) Maverick, E.; Cram, D. J. In ComprehensiVe Supramolecular
Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F.,
Lehn, J.-M., Eds.; Elsevier: New York, 1996; Vol. 2.
10.1021/ol026780t CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/11/2002

and they are held by chain lengths sufficiently long to allow
a window functioning as a passage for a guest, this kind of
host may hold a cation firmly in its cavity and still provide
the flexibility of permitting the cation to go in and out of
the cavity interior. We report in this communication the
model design of such a molecular host. The spherical
molecular host 1 is composed of a tetrathia[3.3.3.3]-
paracyclophane bridged by two 18-crown-6 units. The X-ray
single-crystal determination confirms the structure of 1,
indicating that the interior cavity size is sufficiently large to
accommodate a Na+ ion. It is also demonstrated by 1H NMR
spectroscopic studies that this host can encapsulate a Na+
ion in the interior cavity through a slow exchange between
the two crown units.
three signals at δ 150.54, 129.78, and 123.31, were observed
for the aromatic carbon atoms, and the oxyethylene carbon
atoms appeared as two singlets at δ 73.52 and 72.88. The
electrospray ionization mass spectrum (ESI-MS) of the
compound shows an ion at m/z 975.4 ([M + Na]+) that
agrees with the relative molecular mass of 1 (or 2) combining
with a Na+ ion. The above spectral data, however, do not
distinguish between the structures of 1 and 2.
The structure of the isolated product was shown to be in
agreement with 1 by an X-ray crystallographic study, and
its ORTEP drawing is given in Figure 1a. The crystal was
A selectively tetrasubstituted dibenzo-18-crown-6 3 was
first prepared by reacting bis(2-bromoethyl)ether with 3,6-
bis(N-morpholinomethyl)catechol. Conversion of 3 to tet-
raacetate 48 followed by a hydrolysis afforded tetrol 5.
Treatment of 5 with PBr3 gave the desired tetrabromide 6.
The reaction of 6 with thiourea formed the intermediate
tetrathiouronium salt, and subsequent hydrolysis of this salt
yielded the tetrathiol 7. A coupling reaction between tetra-
bromide 6 and tetrathiol 7 was carried out in the presence
of a base under high dilution conditions.9 A pure compound
(2% yield) was isolated by column chromatography followed
by preparative thin-layer chromatography. In principle, 1 and
2 could be formed from linking 6 and 7 perpendicularly and
Figure 1. (a) ORTEP drawing and (b) space-filling drawing of 1.
found to be associated with two water molecules occupying
the packing space. The molecular structure of 1 belongs to
the D2d point group.10 All aromatic rings do not significantly
deviate from planarity, and the C-S bond lengths are
comparable to the reported values in small dithiacyclo-
phanes.11 The two dibenzo-18-crown-6 units in 1 take a
puckered conformation. The dihedral angles for aromatic
rings are 94.0 and 127.1° for opposite and adjacent aryl rings,
respectively. The space-filling drawing of 1 as shown in
Figure 1b illustrates the somewhat spherical nature of this
molecule with an enclosed cavity capped by the two 18-
crown-6 units. The diameter12 of each of the crown ethers
was estimated to be 1.96 Å, and the depth13 of the central
molecular cavity was estimated to be 6.75 Å.
1
in parallel, respectively. The H NMR spectrum of the
isolated product shows a singlet at δ 7.07 for the aromatic
protons Ha and an AB system at δ 3.44 and 3.98 (J ) 14.1
Hz) for the bridge methylene protons Hb and Hc. Interest-
ingly, the magnetically nonequivalent oxyethylene protons
(-OCHdHeCHfHgO-) appear as four groups of separated
signals, three of which are well-resolved, and one appears
as a broad signal at δ 3.45-3.60. In its 13C NMR spectrum,
1
The H NMR spectra (Figure 2) of 1 upon addition of
potassium, sodium, and lithium picrate were examined in
2:1 v/v CD3CN/CDCl3. The spectra of 1 upon addition of
(8) A major byproduct, 1,5-bis(2-acetoxy-6-acetoxymethylphenoxy)-3-
oxa-pentane, was also isolated.
(9) Rossa, L.; Vo¨gtle, F. Top. Curr. Chem. 1983, 113, 1.
(10) In addition to the C2 and S4 axes joining the centers of the two
crown rings, there are two additional C2′ axes each joining two diagonal
sulfur atoms that are perpendicular to the C2 axis and two dihedral planes
(σd) that lie between the C2′ axes. Thus, this molecule belongs to the D2d
point group.
(11) Anker, W.; Bushnell, G. W.; Mitchell, R. H. Can. J. Chem. 1979,
57, 3080.
(12) This was estimated by averaging the difference of all diagonal
distances of oxygen atoms and the van der Waals diameter of an oxygen
atom (2.8 Å).
(13) This was estimated by measuring the distance between the centers
of the two crown rings.
3912
Org. Lett., Vol. 4, No. 22, 2002

Figure 3. 1H NMR (500 MHz) spectra of 1 upon addition of Na+
ion in 1:2 v/v CDCl3/CD3CN at (a) 300 K, (b) 273 K, (c) 263 K,
(d) 253 K, and (e) 243 K ([1] ) 1.4 × 10-3 mol/dm3; [sodium
picrate] ) 7 × 10-3 mol/dm3; (b) complexed signals, (O)
uncomplexed signals).
Figure 2. 1H NMR (400 MHz) spectra of (a) free 1 and upon
subsequent addition of (b) Na+, (c) K+, (d) K+ followed by Na+,
(e) Li+, and (f) Li+ followed by Na+ (1:2 v/v CDCl3/CD3CN; 300
K; [1] ) 1.4 × 10-3 mol/dm3; [metal picrate] ) 7 × 10-3 mol/
dm3.
K+ or Li+ ion did not suffer any significant change. The
spectrum of 1 upon addition of Na+ ion, however, exhibited
severe broadening in the aliphatic region where two doublets
(CH2S) and four groups of multiplets (OCH2) overlapped
significantly and lost all distinct splitting patterns observed
signals due to significant overlapping. It is thus believed that
the pair of singlets at δ 7.12 and 7.14 is derived from a Na+/
1-complexed species rather than new conformers of free 1
resulted from a change in temperature.
The singlet at δ 7.10 in the spectrum at 300 K (Figure
3a) should represent an averaged signal of the two partially
resolved signals observed at 273 K (Figure 3b) corresponding
to an exchange between complexed 1 and free 1. The
diameter of each crown cavity in 1 is about 1.96 Å, which
is close to that of a Na+ ion (1.90 Å) but significantly smaller
than of a K+ ion (2.66 Å). Although no X-ray crystal-
lographic data of the 1‚Na+ complex is available, the Na+
ion is likely to go into the central cavity of molecule 1,
whereas the significantly larger K+ ion may fail to do so.
Due to the electrostatic repulsion of two positively charged
Na+ ions and a relatively small inner cavity size of host 1,
the formation of a 1:2 complex between 1 and Na+ ions
seems unlikely. This postulation is also supported by results
derived from an ESI-MS spectroscopic study of 1 in the
presence of a mixture of alkali metal (Li+, Na+, and K+)
picrates. The base peak was observed at m/z ) 975 for the
1
in the spectrum of free 1. The H NMR spectra of 1 upon
addition of K+ or Li+ ion, followed by Na+ ion, showed the
same spectral characteristics as that of 1 in the presence of
only Na+ ion. Accordingly, this competitive complexation
experiment indicates that host 1 has a stronger preference
to binding Na+ ion than K+ or Li+ ion. We believe the
significant broadening in the aliphatic proton signals is due
to some kind of slow exchange processes between 1 and
Na+ ion on the NMR time scale at room temperature. In
some pseudorotaxane systems, broad signals in their 1H NMR
spectra at room temperature were also observed as a result
of slow exchange rates between host and guest.14
To further investigate the complexation behavior of the
spherical host 1 and Na+ ion, dynamic 1H NMR spectra were
determined from 300 to 243 K (Figure 3). At 300 K, the
aromatic protons were observed as a broad singlet at δ 7.10
that was partially resolved into two broad signals at 273 K.
Further cooling to 243 K resulted in “a pair” of singlets at
δ 7.12 and 7.14 and a relatively broader singlet at δ 7.07.
The above observation is qualitatively consistent with two
successive exchange processes between the host (1) and guest
(Na+). The “pair” of singlets (at 243 K) is assigned to
aromatic protons of complexed host 1 and the broad singlet
to those of uncomplexed 1. This is also supported by a
constant 1:1 integration ratio of one doublet at ca. δ 4.0 and
the aromatic singlet at ca. δ 7.08 in the temperature range
from 263 to 243 K for the uncomplexed host. However, it
is impractical to differentiate the other oxyethylene proton
+
[1 + Na] ion, but no 1:2 stoichiometric binding species
was detected. A relatively weaker (30-35%) peak was
observed at m/z 991 corresponding to the [1 + K] + ion, but
no indication of a [1 + Li]+ ion was detected. The former
could be derived from a weak external complexation of 1 to
a K+ ion, but it is unlikely to be a centrally trapped 1‚K+
complex as shown by the 1H NMR studies discussed earlier
(Figure 2). Since the 1‚Na+ complex is in a slow exchange
with the uncomplexed species, its association constant (Kass)
1
could be estimated by direct H NMR analysis to be about
12 M-1 at 263 K on the basis of the integration ratio of their
aromatic proton signals.
The second exchange process is likely to be an intramo-
lecular phenomenon after the host 1 complexes to a Na+
ion. The two well-resolved singlets at δ 7.12 and 7.14 with
equal integration areas suggest that, at the low-temperature
limit (243 K; Figure 3), the Na+ ion is only complexed to
(14) (a) Ashton, P. R.; Chrystal, E. J. T.; Glink, P. T.; Menzer, S.;
Schiavo, C.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; Whitle, A. J. P.;
Williams, D. J. Chem. Eur. J. 1996, 2, 709. (b) Chang, T.; Heiss, A. M.;
Cantrill, S. J.; Fyfr, M. C. T.; Pease, A. R.; Rowan, S. J.; Stoddart, J. F.;
White, A. J. P.; Williams, D. J. Org. Lett. 2000, 2, 2947.
Org. Lett., Vol. 4, No. 22, 2002
3913

represents one of the rare examples of a molecular structure
belonging to the D2d point group.16 The host 1 shows a
selective preference for complexation with a Na+ ion in the
presence of other alkali cations. The Na+ ion is essentially
trapped in the central cavity of the molecule through a novel
and unique exchange between the two crown units. At higher
temperatures, there exists another exchange process whereby
the Na+ ion could diffuse into the solution from the host.
Thus, molecule 1 should serve as a good model of a host
with preferred binding to one type of cation like the
carcerands and still allow the guest to “communicate” with
the external environment. In addition, the temperature factor
may be used to tune the degree of complexation or diffusion
of the guest to or from the host.
Figure 4. Intramolecular kinetic equilibrium between host 1 and
guest Na+.
one of the two crown units in 1, resulting in magnetically
nonequivalent aromatic protons between the complexed
crown and the free crown. Increasing the temperature led to
the collapse of the pair of singlets, which reappeared as an
averaged broad signal at 273 K. This should correspond to
a kinetic equilibrium, with the guest Na+ ion exchanging
complexation sites between the two intramolecular “front”
and “back” crown hosts as illustrated in Figure 4. The free
energy of activation (∆Gcq) for this process could be
estimated by the coalescence temperature (Tc) method.
Employing the pair of noncoupled aromatic signals as a probe
allowed ∆Gcq to be estimated as 14.1 ( 0.3 kcal/mol (Tc )
268 ( 5 K, ∆ν ) 8 Hz) on the basis of the Eyring equation.15
In conclusion, the spherical molecule 1 was successfully
synthesized as a model compound for our investigation. It
Acknowledgment. This work was supported by the
National University of Singapore (RP-143-000-026-112). We
thank Associate Professor Ang Siau Gek and Ms. Tan Geok
Kheng for their assistance in the determination of the single-
crystal structure.
Supporting Information Available: Crystallographic
data of 1 and experimental preparations for compounds 1-6.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL026780T
(16) There were only a few reported examples of supramolecular hosts
with D2d symmetry; see: (a) MacGillivray, L. R.; Atwood, J. L. Angew.
Chem., Int. Ed. 1999, 38, 1018. (b) Wyler, R.; Mendoza, J. D.; Rebek, J.,
Jr. Angew. Chem., Int. Ed Engl. 1993, 32, 1699.
(15) kc ) π∆ν/x2 and ∆Gcq ) 2.303 × RTc(10.319 + log Tc - log kc);
see: Calder, I. C.; Garratt, P. J. J. Chem. Soc. B 1967, 660.
3914
Org. Lett., Vol. 4, No. 22, 2002