A new fluorescent calix crown ether: Synthesis and complex formation with alkali metal ions

Article abstract of DOI:10.1002/chem.200701018

We synthesised a new N-benzylaza-21-crown-7 ether 5 with a dihydroxy coumarin as a fluorescence sensor and investigated the binding behaviour towards alkali metal cations in methanol by fluorescence titrations. The association constants are within one order of magnitude, with the exception of sodium. Potassium is the preferred binding partner (K_Na= 330_M-1; K_K=8600_M-1; K_Rb=8200_M-1; K _Cs=4400_M-1). The corresponding aza-21-crown-7 ether (6) was attached by a methylene unit to a resorcarene to give fluorescent calix crown ether 12. The binding abilities of the calix crown ether towards alkali metal ions in methanol have also been investigated, and an increasing complex stability, distinct for potassium and rubidium in comparison with 5, was found: K_Na= 440_M-1; K_K = 110000_M-1; K _Rb = 63000_M-1; K_Cs= 20000_M-1. Like bis(crown ether)s, a cooperative complexation of the crown ether and the cavitand scaffold can be assumed. The proposed complex geometry is supported by Kohn-Sham DFT calculations for the potassium and caesium complexes.

Full text of DOI:10.1002/chem.200701018

FULL PAPER
DOI: 10.1002/chem.200701018
A New Fluorescent Calix Crown Ether: Synthesis and Complex
with Alkali Metal Ions
A
Ion Stoll,[a] Jens Eberhard,[a] Ralf Brodbeck,[b] Wolfgang Eisfeld,[b] and Jochen Mattay*[a]
Abstract: We synthesised a new N-ben-
zylaza-21-crown-7 ether 5 with a dihy-
21-crown-7 ether (6) was attached by a
methylene unit to a resorcarene to give
fluorescent calix crown ether 12. The
binding abilities of the calix crown
ether towards alkali metal ions in
methanol have also been investigated,
and an increasing complex stability, dis-
tinct for potassium and rubidium in
droxy coumarin as
a
fluorescence
comparison with 5, was found: KNa
440mꢀ1 KK =110000mꢀ1
KRb
63000mꢀ1
=
sensor and investigated the binding be-
haviour towards alkali metal cations in
methanol by fluorescence titrations.
The association constants are within
one order of magnitude, with the ex-
ception of sodium. Potassium is the
;
;
=
;
K
Cs =20000mꢀ1. Like bis-
(crown ether)s, a cooperative complex-
ation of the crown ether and the cavi-
tand scaffold can be assumed. The pro-
posed complex geometry is supported
by Kohn–Sham DFT calculations for
the potassium and caesium complexes.
Keywords: crown compounds
fluorescence sensors · host–guest
systems sandwich complexes
supramolecular chemistry
·
preferred binding partner (KNa
330mꢀ1; KK =8600mꢀ1; KRb =8200mꢀ1
Cs =4400mꢀ1). The corresponding aza-
=
·
·
;
K
Introduction
pramolecule will be formed. However, knowledge of inter-
actions of the cavitand with small guest molecules in solu-
tion are limited and the strength of the interaction is
minor.[9] For this reason more sophisticated supramolecules,
starting from cavitands, are necessary. Popular examples,
analogous to phenol calixarenes,[10] are the combination of a
cavitand with a crown ether,[11] and the incorporation of cav-
itands in crown ethers.[12,13] The binding abilities of crown
ethers and aza crown ethers are well-established,[14] as is
their use as sensors.[15]
Herein, we present the synthesis and binding studies of a
novel fluorescent N-benzylaza-21-crown-7 ether with a dihy-
droxy coumarin chromophore.[16–18] Based on this crown
ether, we synthesised the first fluorescent cavitand crown
ether and also carried out binding studies in solution. Con-
formations of the complexes formed were investigated by
DFT calculations.
Resorc[4]arenes are important in the field of supramolecular
chemistry and have been the subject of a number of re-
views.[1] They are used as host systems for noncovalent inter-
actions, and moreover, as building blocks for extended su-
pramolecules like carcerands,[2,3] deepened cavitands[4] and
other large receptor molecules.[5] The driving forces for non-
covalent interdependence are cation–p, CH–p and hydro-
ꢀ
ꢀ
phobic interactions as well as C H and O H hydrogen
bonds.[6,7] The latter might be the most significant driving
force, and therefore, the supramolecular chemistry of resor-
c[4]arenes with unfunctionalised hydroxyl groups differs
considerably from functionalised ones, such as the cavi-
tand.[8] Owing to the shape of the cavitand, it is highly
tempting to expect that a crown ether-like, p-electron-donat-
ing all-in-one device, which is suitable for an all-purpose su-
[a] I. Stoll, J. Eberhard, Prof. Dr. J. Mattay
Organische Chemie I. Fakultät für Chemie, Universität Bielefeld
Postfach 100131, 33501 Bielefeld (Germany)
Fax : (+49)521-6417
Results and Discussion
7,8-Dihydroxycoumarin (1) was prepared according to a
procedure by Sugimo and Tanaka.[19] The synthesis of the
benzo crown ether was carried out in an analogous manner
to that reported by Gokel et al. (Scheme 1).[20] Triethylene
glycol tolylsulfonyl ether (2) was used to attach the glycol
units to the coumarin hydroxyl groups to give 3. Tosylation
E-mail: oc1jm@uni-bielefeld.de
[b] Dr. R. Brodbeck, Dr. W. Eisfeld
Theoretische Chemie, Fakultät für Chemie, Universität Bielefeld
Postfach 100131, 33501 Bielefeld (Germany)
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2008, 14, 1155 – 1163
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1155

Scheme 3. Monofunctionalisation of the resorcarene scaffold. a) i) 1 equiv
n-butyllithium, THF, ꢀ788C, 1.5 h; ii) methyl chloroformate, 12 h, RT;
b) i) LiAlH4, THF, 3.5 h, 608C; ii) 12 h, RT.
Scheme 1. Synthesis of luminescent crown ether 5. a) K2CO3, DMF;
b) TsCl, NEt3, CH2Cl2; c) K2CO3/Cs2CO3, benzyl amine, MeCN, 808C,
39 h.
This step was the problematic stage of the synthesis. In the
simple case with four methyl esters, ambient conditions
were sufficient.[24] In our case there are three remaining bro-
mines on the resorcarene moiety. Their removal requires
higher reaction temperatures and causes formation of by-
product 10. With increasing reaction time, concurrent bro-
mine removal and opening of the cavitand can be monitored
by MALDI-TOF mass spectrometry. We tried to control the
conditions in favour of benzyl alcohol 9, but so far our en-
deavours have not been successful.
and cyclisation using benzyl amine finally gave crown ether
5. For further synthetic steps the benzyl group has to be re-
moved. Benzyl groups are prevailing protecting groups for
aza crown ethers and are generally removed by hydrogena-
tion (Scheme 2).[21]
The reaction was carried out several times with only fair
yields of up to 34% of 9. Treatment of the methyl ester with
LiAlH4 for only a few minutes followed by removal of bro-
mine in a further reaction by successive addition of n-butyl-
lithium and methanol gave the best results. However, forma-
tion of byproduct 10 could still not be suppressed complete-
ly.
Substitution of the hydroxyl group of 9 proceeds in
almost quantitative yield to give benzyl bromide 11, whereas
subsequent substitution to form calix crown ether 12 pro-
ceeds with the expected moderate yield for nucleophile sub-
stitution reactions with aza crown ethers. In addition, the
isolated yield is reduced by the efficient chromatographic
workup (Scheme 4).
Scheme 2. Removal of the benzyl protecting group. a) HCl, Pd/C, iPrOH,
508C, 45 min.
1H NMR spectra of 12 are shown in Figure 1. The spec-
trum in Figure 1a shows 12 purified by column chromatogra-
phy on silica gel. Silica gel provides cations on the surface,
and hence, broadened resonances of the host protons as a
result of complexed ions are observed. Most apparent is the
broadening of the signals that belong to the methylene unit
located between two phenolic oxygen atoms (arrows at low
Tetrabromo cavitand 7[22] was treated with one equivalent
of n-butyllithium and equilibrated for two hours to control
the product distribution to the mono-functionalised species
(Scheme 3). Subsequently, methyl chloroformate was
added.[23] Methyl ester 8 was reduced with LiAlH4 in THF.
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Chem. Eur. J. 2008, 14, 1155 – 1163

Fluorescent Calix Crown Ether
FULL PAPER
spectra appear owing to the change of the excited-state
dipole.[25] In contrast, dihydroxy coumarin cryptands are re-
ported to act as photoinduced-electron-transfer (PET) sen-
sors.[16] Upon cation binding or protonation, these com-
pounds show an enhanced fluorescence intensity. This indi-
cates a PET mechanism by electron transfer from the nitro-
gen lone pair to the coumarin in the non-complexed form.
We investigated the PET activity for our fluorescence sys-
tems 5 and 12 by titration with trifluoroacetic acid, which
demonstrates the absence of PET. Only minor changes were
observed after addition of multiple equivalents of trifluoro-
acetic acid. It seems that the nitrogen lone pair is too far
away from the coumarin unit for an efficient electron trans-
fer. Hence, we assume a PCT mechanism for both host sys-
tems.
The absorption spectrum of 5 shows the typical shape of a
7,8-substituted coumarin, with an absorption maximum at
316 nm, a small maximum at 253 nm, and a maximum in the
region of aromatic absorbance at 210 nm. The emission
maximum is at 452 nm (Figure 2).[26,27]
The absorption and emission spectra of calix crown ether
12 is shown in Figure 3. Aside from an absorption at
Scheme 4. Synthesis of luminescence host 12. a) PBr3, CH2Cl2, 1 h, RT;
b) Cs2CO3, DMF, 808C, 44 h.
Figure 2. Absorption (c) and emission (a) spectra of coumarin
crown ether 5 in methanol (c=5”10ꢀ5 m, bandwidth=0.5 nm). Raman
and Rayleigh peaks are not removed.
Figure 1. 1H NMR spectra of 12 in CDCl3, 500 MHz. a) Prior to and
b) after filtration through basic alumina.
field). In a similar way, but to a lesser extent, most of the
other signals are also broadened and/or shifted. After filtra-
tion through basic alumina, which is a standard chromato-
graphic procedure in crown ether chemistry, the cations are
detached and the resonances are now well resolved (Fig-
ure 1b).
Crown ethers that contain a coumarin fluorophore are
known as photoinduced-charge-transfer (PCT) cation sen-
sors. Upon cation binding, spectral changes in the emission
Figure 3. Absorption (c) and emission (a) spectra of calix crown
ether 12 in methanol (c=1”10ꢀ5 m, bandwidth=0.5 nm). Raman and
Rayleigh peaks have not been removed. Inset: Absorption spectrum of
C-undecylcavitand in methanol.
Chem. Eur. J. 2008, 14, 1155 – 1163
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1157

J. Mattay et al.
316 nm, two poorly resolved absorption bands appear at 286
and 276 nm. These maxima result from the resorcarene
moiety, as shown by comparison to the absorption spectrum
of an unsubstituted cavitand (Figure 3, inset and the litera-
ture[22]). The maximum at 452 nm of the emission spectrum
is analogous to 5.
Crown ether 5 and calix crown ether 12 were titrated with
solutions that contained different alkali metal acetates to
determine binding constants. For example, the emission
spectra of 12 recorded after the addition of potassium ace-
tate is shown in Figure 4.
*
Figure 5. Measured ( ) and calculated (c) fluorescence intensity of
the potassium complex of 12. Inset: Job plot for the complex of 12 with
potassium (coverall =1”10ꢀ5 m).
Figure 4. Emission spectra of 12 in methanol upon addition of potassium
acetate solution.
The association constants for a 1:1 complex were calculat-
ed from non-linear curve fitting by iterative solution of
Equation (1):
Figure 6. ESI mass spectrum of 12 and sodium, potassium and caesium
chlorides in methanol (chost =1”10ꢀ5 m, cguest =1”10ꢀ2 m).
IlimꢀI0
1
I ¼ I0 þ
ꢀ
=
2
½HŠ
0
ð1Þ
ꢁ
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
½HŠ0 þ ½GŠ þ Kꢀ1
ꢀ
ð½HŠ0 þ ½GŠ þ Kꢀ1Þ ꢀ4½HŠ ½GŠ
2
give any proof for the formation of
a 1:2 complex
0
(Figure 6). A doubly charged 1:2 complex would appear, de-
pending on the guest cations, in the range m/z 810–935. Fi-
nally the complex stoichiometry was assured by a represen-
tative Job plot[29] for the complex of 12 with potassium (cK+
12 =1”10ꢀ5 m).
Equation (1) gives the relationship between the fluores-
cence intensity I, and the association constant K. [H0] is the
initial host concentration and [G] is the guest concentration.
The initial fluorescence intensity, I0, is measured from the
host emission spectra in the absence of guest. The final in-
tensity, Ilim, was ascertained by measurement of the saturat-
ed complex fluorescence intensity or was treated as a float-
ing parameter. A detailed derivation of Equation (1) and
further information can be found in the literature.[28]
The addition of an alkali metal solution (0.01, 0.05, 0.1
and/or 0.5m, see Experimental Section) in methanol to a so-
lution of the host system in methanol (1.0”10ꢀ5 m) results in
a decreasing fluorescence intensity at a given excitation
wavelength. The plot of fluorescence intensity of host 12
versus potassium concentration is shown in Figure 5.
Discussion
The binding constants for various alkali metal complexes
with host systems 5 and 12 are summarised in Table 1. For
all titration plots the coefficient of determination is higher
than 0.99. Alkali acetates were used because of their high
solubility. The same results were obtained by using potassi-
um and caesium chlorides, which indicates that the counter-
ion does not have an influence.
The association constant of the potassium complex ex-
ceeds the association constant for the other alkali metal
complexes for both host systems. The preference of N-ben-
zylaza-21-crown-7 for potassium compared with caesium
A 1:1 complex can be estimated by the shape of the bind-
ing isotherm. There was no evidence of a 1:2 (H/G) complex
during our work. For example, ESI-MS studies could not
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Fluorescent Calix Crown Ether
FULL PAPER
Table 1. Association constants of 5 and 12 in methanol with various
alkali metal acetates at 258C.
try, we assume that 12 forms a sandwich-like complex geom-
etry with larger alkali metal cations.
Compound
Guest
K [mꢀ1
(4.4ꢁ0.6)”102
(1.1ꢁ0.2)”105
(6.3ꢁ0.5)”104
(2.0ꢁ0.1)”104
(3.3ꢁ0.6)”102
(8.6ꢁ1.1)”103
(8.2ꢁ0.8)”103
(4.4ꢁ0.9)”103
]
log K
R2
In principle, there are two possible enthalpic contributions
for an increased binding constant for a calix crown ether
sandwich complex: 1) cooperative complexation that in-
volves few or several resorcarene oxygen atoms and crown
ether oxygen atoms to form a suitable coordination sphere
for the cation, and 2) stabilisation through cation–p interac-
tions by the aromatic rings of the resorcarene. To evaluate
this and gain further insight into the structural difference of
the complexes of 12 formed with different alkali metal ions,
we examined selected complexes by structure optimisation
and harmonic normal mode analysis in the frameworkof
Kohn–Sham DFT (for details see the Experimental section).
Calculations were carried out for the potassium and caesium
complexes of 12, starting from a sandwich-like complex ge-
ometry. For the calculations a model compound of 12 was
used. The lower rim n-undecyl groups were replaced by
methyl groups, but this has no influence on the rigid resorc-
Na+
K+
G
2.64ꢁ0.06
5.03ꢁ0.08
4.80ꢁ0.03
4.29ꢁ0.03
2.51ꢁ0.06
3.93ꢁ0.06
3.91ꢁ0.04
3.64ꢁ0.07
0.994
0.997
0.997
0.999
0.994
0.994
0.995
0.991
AHCTREUNG
12
Rb+
Cs+
Na+
K+
ACHTREUNG
AHCTREUNG
AHCTREUNG
AHCTREUNG
5
Rb+
Cs+
ACHTREUNG
AHCTREUNG
and sodium has also been reported before by means of calo-
rimetric titrations, and is in very good agreement with our
results.[30] The caesium ion is not appropriate for the provid-
ed coordination sphere, and therefore, weaker complexes
are formed. Stronger complexes are formed with potassium
and rubidium. Sodium is too small for efficient binding to
the crown ether. The results are also in good agreement
with the Shannon ionic radii.[31] We assume that the slightly
smaller association constants for 5 compared with those re-
ported for N-benzylaza-21-
AHCTREUNG
crown-7 are as a result of the
reduced flexibility caused by
the incorporated coumarin unit.
However, the preference to-
wards potassium and rubidium
over caesium and sodium is still
confirmed.
The association constants for
the alkali metal–calix crown
ether complex are one order of
magnitude larger than those of
the corresponding crown ether
complexes, except for the
sodium complex. The associa-
tion constant of the potassium
complex noticeably exceeds
that of the caesium and rubidi-
um complexes of 12. In summa-
ry, both host systems show the
highest selectivity towards po-
tassium and the binding affinity
is increased by the attached
Figure 7. Calculated structures for the potassium and caesium complexes of 12.
cavitand. The preference for
sodium is only weakly influ-
enced by the cavitand, presum-
Because van der Waals and other dispersive interactions
are not correctly described by the approximate exchange-
correlation functionals currently used,[34] complexation ener-
gies were not calculated. As mentioned above, the measured
association constants are in agreement with a sandwich-like
complex geometry. Therefore, conformational isomers of 12
whose crown ether covers the resorcarene were chosen.
These conformations are energetically most favourable and
should be important in solution. The metal cations find
many possible coordination sites in these structures, which
results in many attracting local minima in structure optimi-
ably for the reasons mentioned above.
Sandwich complexes formed from two crown ethers or a
bis(crown ether) and one cation are known, especially for
big cations.[32] For bis(crown ether)s the binding ability to-
wards a cation is enhanced owing to the entropic term by
formation of an intramolecular sandwich complex. The ob-
served difference of the binding constants of alkali metal
complexes of 5 compared with the alkali metal complexes of
12 are in good agreement with bis(crown ether) com-
plexes.[33] From this and the established complex stoichiome-
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J. Mattay et al.
Acros Organics; rubidium acetate 99.8%, purchased from Alfa Aesar;
sodium and potassium acetate 99%, Merck) solutions in methanol (1 and
2 mL of a 0.01m solution; 1 and 5 mL of a 0.1m solution; 1 mL of a 0.5m
solution in the case of sodium to reach complex saturation) were added.
This led to a host/guest ratio ranging from 1:1 to at least 1:250 at satura-
tion concentration. The cuvette was shaken for 1 min and was allowed to
equilibrate for an additional 1 min. After each addition spectra were re-
corded until complex saturation was reached. Care was taken to increase
the reaction volume less than 6%. The excitation wavelength was 318 nm
and the monochromator bandwidth was set to 4 nm for the excitation
and the emission monochromator. All spectra were recorded by using a
Perkin–Elmer LS50B luminescence spectrometer and a Perkin–Elmer
Lambda 40 UV/Vis spectrometer. For Equation (1) integrated fluores-
cence intensities were used. Integrations were carried out with the soft-
ware Spekwin32[35] from the isoemissive point to the baseline (625 nm).
This approach was used for the sake of precision caused by the slight
blueshift.
sations. Hence, two coordination isomers were preselected
as starting configurations: in the first one the cation was
closer to the aza crown ether and in the second isomer it
was closer to the resorcarene. For the potassium complex
two minima were found, but for the caesium complex only
one minimum could be located for coordination by the calix
crown ether (Figure 7). For the illustration the Shannon
ionic radii for the sixfold coordinated potassium and the
eightfold coordinated caesium were used. The resorcarene
atoms are displayed in 33% van der Waals radii. The first
minimum of the potassium complex is only 2 kcalmolꢀ1
lower in energy than the second minimum (which includes a
zero-point energy correction). The (effective) coordination
number for the first minimum is seven and the K···O distan-
ces (of coordinating oxygen atoms) range from 282 to
299 pm (oxygen atoms 1, 4, 7, 13, 16, 19, d). For the second
minimum the coordination number is six and the K···O/N
distances are from 277 to 311 pm (oxygen/nitrogen atoms 1,
4, 7, 10, a, d). This does not prove, but makes plausible, a
sixfold coordination in solution. For the caesium complex
the coordination number is eight. The Cs···O distances (of
coordinating oxygen atoms) range from 311 to 375 pm
(oxygen atoms 1, 4, 7, 13, 16, 19, c, d). As is to be expected,
in all three compounds the metal cations coordinate to
oxygen atoms of the aza crown ether and of the resorcarene.
Only a few resorcarene oxygen atoms seem to participate.
In summary, the crown ether oxygen atoms and the resorcar-
ene oxygen atoms are able to form different coordination
spheres, which are dependent on the size of the guest.
Details of calculations: The Kohn–Sham DFT calculations reported
herein were performed with the Gaussian 03 program,[36] using the
B3LYP[37] hybrid density functional (with the VWN-III, not the VWN-V
functional), which is known to give reasonable equilibrium structures and
normal mode frequencies for many compound classes.[34] To reduce the
number of necessary basis functions, effective core potentials (ECP) and
corresponding basis sets, of Stevens et al.[38] for H (only basis set, no
ECP), C, N and O, and of Preuss et al.[39] for K and Cs, were used. The
basis sets of C, N and O were augmented with polarisation functions (for
K and Cs these are already part of the basis sets). For the structure opti-
misations, an integration grid of 99 radial shells with 590 angular points
per shell for all atoms (pruned for nonmetals, unpruned for metals) was
used. The threshold for maximum force was 4.5”10ꢀ4 a.u., the threshold
for maximum displacement in internal coordinates was 1.8”10ꢀ3 a.u. This
leads to equilibrium structures with energies consistent to 10ꢀ7 a.u. (the
same accuracy as for the electronic energy). In the normal mode analyses
the integration grid accuracy was reduced to 75 radial shells with 302 an-
gular points per shell (pruned for nonmetals, unpruned for metals). All
theoretical structures reported herein were confirmed to be true minima
by harmonic normal mode analysis. Throughout this workwe used the
charge density fitting approximation for Coulomb integrals[40] with auto-
matically generated auxiliary basis sets and the Gaussian Fast Multipole
Method.[41] Cartesian coordinates and electronic energies are available in
the Supporting Information.
Conclusions
We have presented the synthesis of a new fluorescence sens-
ing crown ether (5) and the first fluorescence sensing calix
crown ether (2) based on a resorcarene scaffold. The com-
plexation abilities of the host systems towards alkali metal
cations in methanol were studied in great detail by fluores-
cence titration and clearly show a size-dependent selectivity.
An incorporation of the cavitand into the supramolecular
host system increases the strength of the complexes formed.
Based on these results, we assume that there is a coopera-
tive effect in complex formation of 12 by the resorcarene
scaffold and the crown ether moiety. This assumption was
confirmed by DFT calculations for the complexes of 12 with
potassium and caesium.
Toluene-4-sulfonic acid 2-[2(hydroxy-ethoxy)ethoxy]ethyl ester (2):
p-Toluenesulfonic acid chloride (12.88 g, 68 mmol) was added portion-
wise to a solution of triethylene glycol (40.02 g, 267 mmol) and triethyl-
amine (13.82 g, 137 mmol) in methylene chloride (100 mL) at 08C. The
solution was stirred for 2 h at this temperature. The organic layer was
washed with saturated NaHCO3 solution and was dried over anhydrous
MgSO4. After evaporation the crude product was purified by flash
column chromatography (SiO2, chloroform/methanol 98:2) to yield a col-
ourless oil (13.91 g, 46 mmol, 68%). 1H NMR (CDCl3, 500 MHz, 278C):
3
3
d=7.77 (d, J=8.2 Hz, 2H; ArH), 7.31 (d, J=8.2 Hz, 2H; ArH), 4.13 (t,
3J=5.2 Hz, 2H; OCH2CH2OTs), 3.68 (t, 3J=5.6 Hz, 2H; OCH2CH2O),
3.67 (t, 3J=6.3 Hz, 2H; OCH2CH2O), 3.57 (brs 4H; OCH2CH2O), 3.54
(t, 3J=5.2 Hz, 2H; OCH2CH2O), 2.41 (s, 3H; CH3), 2.28 ppm (s, 1H,
OH); 13C NMR (CDCl3, 125 MHz, 278C): d=144.8, 132.9, 129.8, 127.9,
72.4, 70.7, 70.2, 69.1, 68.6, 61.7, 21.6 ppm.
7,8-Bis(2-{2-[2-hydroxyethoxy]ethoxy}ethoxy)-4-methyl-2H-chromen-
2-on (3): K2CO3 (4.74 g, 34.3 mmol) was suspended in a solution of 1
(3.00 g, 15.6 mmol) and 2 (10.45 g, 34.3 mmol) in N,N-dimethylformamide
(75 mL). The solution turned yellow and was stirred for 23 h at 808C
under an argon atmosphere. The solvent was removed in vacuo and the
residue was dissolved in water (150 mL). The acidity was adjusted to
pH 3 with dilute HCl. The aqueous phase was extracted with methylene
chloride (5” 50 mL) and the combined organic phase was dried over an-
hydrous MgSO4. After evaporation the crude product was purified by
flash column chromatography (Al2O3, methylene chloride/diethyl ether/
ethanol 2:2:1) to give a yellowish oil (5.94 g, 13.0 mmol, 83%). 1H NMR
(CD3OD, 500 MHz, 278C): d=7.46 (d, 3J=9.0 Hz, 1H; ArH), 7.08 (d,
Experimental Section
General procedure for fluorescence titrations: A solution of the host
system was prepared in methanol (c=1.0”10ꢀ5 m). Methanol=99.9%,
A.C.S. spectrophotometric grade, was purchased from Aldrich and used
as received. The host solution (1.0 mL) was transferred with a transfer
pipette to a PTFE-stoppered 10”4 mm half micro quartz cuvette from
Hellma. When not in use the cuvette was stored in Caroꢁs Acid. Spectra
were recorded three to five times and accumulated. Subsequently, small
amounts of alkali metal acetate (caesium acetate 99%, purchased from
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Fluorescent Calix Crown Ether
FULL PAPER
3J=9.0 Hz, 1H; ArH), 6.17 (d, 4J=1.3 Hz, 1H; coumarin), 4.31–4.25 (m,
4H; OCH2CH2O), 3.93–3.88 (m, 2H; OCH2CH2O), 3.87–3.83 (m, 2H;
OCH2CH2O), 3.75–3.69 (m, 4H; OCH2CH2O), 3.67–3.59 (m, 8H;
OCH2CH2O), 3.57–3.50 (m, 4H; OCH2CH2O), 3.43 (d, 4J=1.3 Hz, 3H;
coumarin), 3.54 (t, 3J=5.2 Hz, 2H; OCH2CH2O), 2.41 (s, 3H; CH3);
13C NMR (CD3OD, 125 MHz, 278C): d=163.0, 156.2, 155.8, 148.9, 136.7,
121.3, 116.1, 112.6, 111.2, 74.0, 73.70, 73.67, 71.83, 71.76, 71.6, 71.53,
cake was washed with 2-propanol and the solvent was removed in vacuo
to yield a yellowish oil (16 mg, 0.038 mmol, 92%). 1H NMR (CDCl3/
CD3OD 1:1, 500 MHz, 278C): d=7.37 (d, 3J=8.8 Hz, 1H; ArH, coumar-
in), 6.95 (d, 3J=8.8 Hz, 1H; ArH, coumarin), 6.15 (d, 4J=1.3 Hz, 1H;
coumarin), 4.30–4.23 (m, 4H; OCH2CH2O), 3.93–3.87 (m, 4H;
OCH2CH2O), 3.75–3.70 (m, 4H; OCH2CH2O), 3.70–3.61 (m, 8H;
OCH2CH2O), 3.03–2.96 (m, 4H; NCH2), 2.41 ppm (s, 3H; CH3, coumar-
in); 13C NMR (CD3OD/CDCl3 1:1, 125 MHz, 278C): d=162.1, 155.1,
154.5, 148.1, 136.0, 120.7, 115.6, 112.6, 110.3, 73.5, 71.09, 71.06, 70.82,
70.76, 70.6, 69.9, 69.2, 68.0, 67.7, 48.0, 18.9 ppm.
71.47, 70.7, 70.1, 62.2, 18.8 ppm; HRMS (ESI): m/z: calcd for C22H32O10
+
H+ [M+H]+ 457.20682; found: 457.20655; IR (ATR): n¯ =3253, 2867,
1716, 1605, 1564, 1507, 1448, 1386, 1374, 1299, 1247, 1106, 1064, 936, 880,
860, 848, 806 cmꢀ1
.
C-Undecyltribromomethoxycarbonylcavitand (8):
A
solution of 7[22]
7,8-Bis(2-{2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy}ethoxy)-4-methyl-2H-
chromen-2-on (4): A solution of 3 (5.58 g, 12.2 mmol) and triethylamine
(4.74 mL, 34.2 mmol) in methylene chloride (50 mL) was cooled to 08C.
p-Toluenesulfonic acid chloride (6.52 g, 34.2 mmol) was added rapidly
portionwise and the mixture was stirred for 16 h. Water (50 mL) was
added and adjusted to pH 3 with dilute HCl. The aqueous phase was ex-
tracted with methylene chloride (3”) and the combined organic phase
was washed with saturated NaHCO3 solution and dried over anhydrous
MgSO4. The crude product was purified by flash column chromatography
(SiO2; i) chloroform, ii) chloroform/methanol 97:3, iii) chloroform/metha-
nol 94:6) to give a yellowish oil (3.37 g, 4.40 mmol, 36%). 1H NMR
(CDCl3, 500 MHz, 278C): d=7.76 (d, 4H, 3J=8.2 Hz, ArTsH), 7.31 (d,
4H, 3J=8.2 Hz; ArTsH), 7.25 (d, 3J=8.8 Hz, 1H; ArH, coumarin), 6.88
(d, 3J=8.8 Hz, 1H; ArH, coumarin), 6.11 (s, 1H; coumarin), 4.27–4.19
(m, 4H; OCH2CH2O), 4.16–4.08 (m, 4H; OCH2CH2O), 3.87–3.82 (m,
2H; OCH2CH2O), 3.82–3.77 (m, 2H; OCH2CH2O), 3.67–3.62 (m, 8H;
OCH2CH2O), 3.60–3.57 (m, 2H; OCH2CH2O), 3.57–3.53 (m, 2H;
OCH2CH2O), 2.40 (s, 6H; CH3-Ts), 2.36 ppm (s, 3H; CH3, coumarin);
13C NMR (CDCl3, 125 MHz, 278C): d=160.6, 154.6, 152.6, 147.8, 144.84,
144.76, 135.8, 132.9, 132.84, 132.82, 129.82, 129.80, 127.92, 127.90, 119.5,
115.0, 112.4, 109.8, 72.9, 70.8, 70.7, 70.5, 69.6, 69.3, 69.2, 68.9, 68.7, 68.6,
21.6, 18.8 ppm; HRMS (ESI): m/z: calcd for C36H44O14S2 +H+ [M+H]+
765.22452; found: 765.22398; IR (ATR): n¯ =2872, 1725, 1601, 1563, 1506,
1448, 1384, 1352, 1297, 1244, 1174, 1095, 1011, 919, 816, 772, 663,
(4.84 g, 3.29 mmol) in anhydrous THF (125 mL) under an argon atmos-
phere was cooled to ꢀ788C and n-butyllithium (2.3 mL of a 1.6m solution
in hexane, 3.68 mmol) was added rapidly. After 1.5 h methyl chlorofor-
mate (2 mL, 25.8 mmol) was added and the mixture was allowed to warm
to room temperature within 12 h. Methanol (10 mL) was added and the
solvent was removed in vacuo. The residue was dissolved in chloroform
and the organic layer was washed with water (3”) and dried over anhy-
drous MgSO4. Evaporation gave the crude product as a yellow oil. After
column chromatography (SiO2, cyclohexane/ethyl acetate 9:1) the pure
product was obtained as colourless solid (2.6 g, 1.8 mmol, 55%).
1H NMR (CDCl3, 500 MHz, 278C): d=7.13 (s, 1H; ArH), 7.00 (s, 1H;
2
ArH), 7.00 (s, 2H; ArH), 5.92 (d, 2J=7.6 Hz, 2H; OCH2O), 5.78 (d, J=
7.6 Hz, 2H; OCH2O), 4.83 (t, 3J=8.2 Hz, 2H; ArCHAr), 4.77 (t, 3J=
8.2 Hz, 2H; ArCHAr), 4.46 (d, 2J=7.5 Hz, 2H; OCH2O), 4.34 (d, 2J=
7.5 Hz, 2H; OCH2O), 3.88 (s, 3H; OCH3), 2.18–2.11 (m, 8H; CHCH2),
1.35–1.20 (m, 72H; CH2), 0.86 ppm (t, 3J=7.6 Hz, 12H; CH3); 13C NMR
(CDCl3, 125 MHz, 278C): d=166.6, 152.5, 152.1, 150.8, 139.3, 139.1,
138.8, 138.6, 124.0, 121.8, 118.9, 118.8, 113.7, 99.0, 98.4, 53.1, 37.6, 36.9,
31.9, 29.9, 29.7, 29.4, 27.7, 22.7, 14.1 ppm; HRMS (ESI): m/z: calcd for
C78H111Br3O10 +Na+ [M+Na]+ 1467.56196; found: 1467.55918; IR (KBr):
n¯ =2925, 2853, 1744, 1538, 1469, 1453, 1301, 1256, 1142, 1092, 1018, 983,
961, 789, 722, 583 cmꢀ1
C-Undecylmonohydroxymethylcavitand (9):
.
A
mixture of 8 (3.82 g,
2.64 mmol) and LiAlH4 (300 mg, 8 mmol) in anhydrous THF (175 mL)
under an argon atmosphere was heated at reflux for 3.5 h and additional
LiAlH4 (150 mg, 2.6 mmol) was added. The mixture was stirred for 12 h
at room temperature and treated with methanol (15 mL). Dilute HCl was
added until the mixture became acidic. The mixture was extracted with
chloroform (3”). The organic layer was washed with saturated NaHCO3
solution and brine, and dried over anhydrous MgSO4. After evaporation
the crude product was purified by column chromatography (SiO2, cyclo-
hexane/ethyl acetate 10:3) to yield a colourless solid (1.07 g, 0.9 mmol,
34%) and byproduct 10 as colourless solid (0.17 g, 0.15 mmol, 5%).
554 cmꢀ1
10-(Benzyl)-22-methyl-2,3,5,6,8,9,11,12,14,15,17,18-
dodecahydrochromenon[7,8-b][1,4,7,13,16,19,10]hexaoxaazacyclohenico-
sin-24(8H)-on (5): A solution of 4 (4.97 g, 6.5 mmol) in dry acetonitrile
.
ACHTREUNG
ACHTREUNG
(100 mL) that contained Cs2CO3 (4.24 g, 13.0 mmol) and K2CO3 (1.80 g,
13.0 mmol) was heated under an argon atmosphere to 808C. Freshly dis-
tilled benzyl amine (0.85 mL, 7.8 mmol) was added and the suspension
was heated for additional 39 h. The solvent was removed in vacuo and
the residue was dissolved in methylene chloride (10 mL) and water
(10 mL). The solution was adjusted to pH 6–7 with dilute HCl. The aque-
ous phase was extracted with methylene chloride (4”) and the combined
organic phase was dried over anhydrous MgSO4. The solvent was re-
moved in vacuo and the crude product was purified by flash column
chromatography (Al2O3; i) diethyl ether/methanol 99:1, ii) diethyl ether/
methanol 97:3) to yield a yellowish oil (0.44 g, 0.83 mmol, 13%).1H NMR
(CD3OD, 500 MHz, 278C): d=7.41 (d, 3J=8.8 Hz, 1H, ArH, coumarin),
7.33–7.16 (m, 5H, ArBnzH), 7.08 (d, 3J=8.8 Hz, 1H; ArH, coumarin),
6.14 (d, 4J=1.3 Hz, 1H; coumarin), 4.29–4.23 (m, 4H; OCH2CH2O),
3.91–3.86 (m, 4H; OCH2CH2O), 3.80–3.53 (m, 16H; OCH2CH2O), 2.79–
2.75 (m, 2H; NCH2), 2.74–2.70 (m, 2H; NCH2), 2.40 ppm (s, 3H; CH3,
coumarin); 13C NMR (CD3OD, 125 MHz, 278C): d=162.9, 156.2, 155.7,
148.8, 136.8, 130.4, 129.2, 128.1, 121.2, 116.0, 112.5, 111.1, 74.1, 72.0,
71.73, 71.67, 71.63, 71.57, 70.6, 70.2, 60.8, 54.8, 54.7, 18.8 ppm; HRMS
(ESI): m/z: calcd for C29H37NO8 +H+ [M+H]+ 528.25919; found:
528.25926; IR (ATR): n¯ =2922, 2867, 1724, 1602, 1562, 1506, 1448, 1384,
1
9: H NMR (CDCl3, 500 MHz, 278C): d=7.12 (s, 1H; ArH), 7.07 (s, 2H;
ArH), 7.07 (s, 1H; ArH), 6.53 (s, 1H; ArH), 6.44 (s, 2H; ArH), 5.80 (d,
2
3
2J=6.9 Hz, 2H; OCH2O), 5.70 (d, J=6.9 Hz, 2H; OCH2O), 4.74 (t, J=
8.2 Hz, 2H; ArCHAr), 4.69 (t, 3J=7.9 Hz, 2H; ArCHAr), 4.66 (d, 3J=
3.1 Hz, 2H; ArCH2) 4.53 (d, 2J=6.9 Hz, 2H; OCH2O), 4.39 (d, 2J=
6.9 Hz, 2H; OCH2O), 2.28–2.11 (m, 8H; CHCH2), 1.67 (t, 3J=3.1 Hz,
3
1H; OH), 1.48–1.20 (m, 72H; CH2), 0.86 ppm (t, J=6.9 Hz, 12H; CH3);
13C NMR (CDCl3, 125 MHz, 278C): d=155.0, 154.7, 154.6, 153.8, 138.3,
138.24, 138.17, 138.1, 125.6, 120.5, 120.4, 116.9, 116.5, 99.9, 99.3, 60.4,
55.1, 36.6, 36.3, 31.9, 29.9, 29.84, 29.75, 29.7, 29.4, 27.9, 22.7, 14.1 ppm;
+
HRMS (ESI): m/z: calcd for C77H114O9 +NH4 [M+NH4]+ 1200.88011;
found: 1200.87999; IR (ATR): n¯ =3337, 2919, 2850, 1609, 1578, 1491,
1459, 1420, 1289, 1181, 1078, 1020, 960, 719, 580 cmꢀ1
.
10: 1H NMR (CDCl3, 500 MHz, 278C): d=7.98 (s, 1H; ArOH), 7.14 (s,
1H; ArH), 7.12 (s, 1H; ArH), 7.11 (s, 1H; ArH), 7.03 (s, 1H; ArH), 6.50
(s, 1H; ArH), 6.44 (s, 1H; ArH), 6.43 (s, 1H; ArH), 5.83 (d, 2J=7.2 Hz,
1369, 1296, 1243, 1202, 1090, 964, 847, 700 cmꢀ1
22-methyl-2,3,5,6,8,9,11,12,14,15,17,18-dodecahydrochromenon
[1,4,7,13,16,19,10]hexaoxaazacyclohenicosin-24(8H)-on (6): N-Benzylaza-
.
2
2
1H; OCH2O), 5.76 (d, J=7.2 Hz, 1H; OCH2O), 5.67 (d, J=7.2 Hz, 1H;
OCH2O), 4.75 (dd, 3J=8.1 Hz, 3J=8.1 Hz, 1H; ArCHAr), 4.69 (dd, 3J=
7.9, 7.9 Hz, 1H; ArCHAr), 4.68 (dd, 2J=11.9, 3J=8.0 Hz, 1H; ArCH2)
4.66 (dd, 3J=8.1, 8.1 Hz, 1H; ArCHAr), 4.56 (dd, 2J=11.9, 3J=8.0 Hz,
1H; ArCH2), 4.48 (d, 2J=7.2 Hz, 1H; OCH2O), 4.41 (d, 2J=7.2 Hz, 1H;
OCH2O), 4.37 (d, 2J=7.2 Hz, 1H; OCH2O), 4.28 (dd, 3J=7.9, 7.9 Hz,
1H; ArCHAr), 3.82 (s, 3H; OCH3), 2.44 (dd, 3J=8.0, 1H; CH2OH),
2.27–2.10 (m, 8H; CHCH2), 1.37–1.16 (m, 72H; CH2), 0.87 ppm (t, 3J=
A
AHCTREUNG
21-crown-7 ether (5) (22 mg, 0.042 mmol) and the same amount in weight
of Pd/C (10% Pd) were suspended in 2-propanol (4 mL) and concentrat-
ed HCl (0.4 mL) was added. The mixture was heated to 508C and stirred
vigorously under a hydrogen atmosphere. The reaction was monitored by
MALDI-TOF and filtered after complete conversion (45 min). The filter
Chem. Eur. J. 2008, 14, 1155 – 1163
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1161

J. Mattay et al.
6.9 Hz, 12H; CH3); 13C NMR (CDCl3, 125 MHz, 278C): d=155.5, 155.0,
154.8, 154.6, 154.4, 153.4, 152.8, 151.3, 138.7, 138.1, 138.0, 137.8, 134.5,
133.3, 129.4, 127.9, 123.1, 121.5, 120.8, 120.3, 120.1, 116.6, 116.5, 106.0,
99.9, 99.5, 99.4, 56.3, 56.0, 36.3, 36.0, 33.7, 33.1, 31.9, 30.3, 29.9, 29.8, 29.7,
29.4, 28.04, 27.98, 27.9, 27.8, 22.7, 14.1 ppm; HRMS (ESI): m/z: calcd for
C77H116O9 +Na+ [M+Na]+ 1207.85116; found: 1207.85067; IR (ATR):
n¯ =3335, 2920, 2851, 1609, 1592, 1492, 1465, 1420, 1290, 1180, 1068, 1019,
[1] a) P. Timmerman, W. Verboom, D. N. Reinhoudt, Tetrahedron 1996,
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.
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113, 2194–2204.
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C-Undecylmonobromomethylcavitand (11):
A
solution of 9 (1.07 g,
0.9 mmol) in dry methylene chloride (25 mL) was treated with phospho-
nium tribromide (0.28 g, 1.03 mmol). The reaction mixture was stirred for
1 h at room temperature and 2-propanol (5 mL) was added. Diethyl
ether (20 mL) was added to the reaction mixture and the solution was
washed with saturated NaHCO3 solution and brine and dried over anhy-
drous MgSO4. Purification by column chromatography (SiO2, cyclohex-
ane/ethyl acetate 9:1) yielded a colourless solid (1.11 g, 0.89 mmol, 99%).
1H NMR (CDCl3, 500 MHz, 278C): d=7.10 (s, 1H; ArH), 7.10 (s, 1H;
ArH), 7.09 (s, 2H; ArH), 6.52 (s, 1H; ArH), 6.46 (s, 2H; ArH), 5.86 (d,
2
3
2J=7.5 Hz, 2H; OCH2O), 5.72 (d, J=7.5 Hz, 2H; OCH2O), 4.72 (t, J=
8.2 Hz, 2H; ArCHAr), 4.70 (t, 3J=8.2 Hz, 2H; ArCHAr), 4.56 (s, 2H;
ArCH2), 4.56 (d, 2J=7.5 Hz, 2H; OCH2O), 4.50 (d, 2J=7.5 Hz, 2H;
OCH2O), 2.27–2.12 (m, 8H; CHCH2), 1.48–1.18 (m, 72H; CH2),
0.86 ppm (t, 3J=6.9 Hz, 12H; CH3); 13C NMR (CDCl3, 125 MHz, 278C):
d=154.9, 154.8, 154.6, 153.7, 138.5, 138.4, 138.2, 137.8, 124.3, 121.4, 120.5,
120.4, 116.9, 116.5, 99.3, 70.9, 36.5, 36.3, 31.9, 30.0, 29.9, 29.84, 29.80, 29.7,
29.4, 27.9, 24.0, 22.7, 14.1 ppm; HRMS (ESI): m/z: calcd for
+
C77H113BrO8 +NH4 [M+NH4]+ 1262.79571; found: 1262.79516; IR
(ATR): n¯ =2916, 2849, 1578, 1489, 1464, 1419, 1284, 1261, 1181, 1154,
1093, 1020, 965, 890, 811, 718, 580 cmꢀ1
.
C-Undecylmono(aza-21-coumarylcrown-7)cavitand (12): A mixture of 6
(33 mg, 0.075 mmol), 11 (94 mg, 0.074 mmol) and Cs2CO3 (50 mg,
0.15 mmol) in dry N,N-dimethylformamide (5 mL) was stirred for 44 h at
808C. The solvent was removed in vacuo. The residue was dissolved in
methylene chloride and water (1:1) and adjusted to pH 7 with dilute
HCl. The organic layer was washed with water (3”) and dried over anhy-
drous MgSO4. Evaporation gave the crude product as a yellow oil. It was
purified by column chromatography (SiO2; i) chloroform/methanol 97:3,
ii) chloroform/methanol 1:1) and the product was filtered through a small
amount Al2O3 (chloroform/methanol 1:1) to detach the complexed ions.
After evaporation a colourless solid was obtained (12 mg, 0.0075 mmol,
10%). 1H NMR (CDCl3, 500 MHz, 278C): d=7.24 (d, 3J=8.8, 1H; ArH,
coumarin), 7.09 (s, 1H; ArH), 7.08 (s, 2H; ArH), 7.03 (s, 1H; ArH), 6.85
(d, 3J=8.8, 1H; ArH, coumarin), 6.45 (s, 1H; ArH), 6.42 (s, 2H; ArH),
6.13 (d, 4J=1.3, 1H; CH, coumarin), 5.76 (d, 2J=6.9 Hz, 2H; OCH2O),
5.71 (d, 2J=6.9 Hz, 2H; OCH2O), 4.69 (t, 3J=8.2 Hz, 4H; ArCHAr),
2
2
4.42 (d, J=6.9 Hz, 2H; OCH2O), 4.29 (d, J=6.9 Hz, 2H; OCH2O), 4.29
(t, 3J=5.3 Hz, 2H; OCH2CH2O), 4.25 (t, 3J=4.4 Hz, 2H; OCH2CH2O),
3.92 (t, 3J=4.4 Hz, 2H; OCH2CH2O), 3.88 (t, 3J=5.3 Hz, 2H;
OCH2CH2O), 3.78–3.55 (m, 12H; OCH2CH2O), 3.43–3.38 (m, 2H;
ArCH2), 2.66–2.76 (m, 4H; NCH2CH2), 2.36 (s, 3H; CH3, coumarin),
2.27–2.08 (m, 8H; CHCH2), 1.46–1.16 (m, 72H; CH2), 0.86 ppm (t, 3J=
6.9 Hz, 12H; CH3); 13C NMR (CDCl3, 125 MHz, 278C): d=169.7, 160.7,
154.9, 154.8, 154.7, 154.2, 152.5, 147.9, 138.4, 138.3, 138.1, 138.0, 135.9,
124.0, 120.63, 120.56, 119.7, 116.6, 116.3, 115.0, 112.5, 109.7, 99.6, 99.5,
72.9, 71.2, 70.8, 70.5, 70.4, 69.6, 69.5, 69.3, 53.3, 48.4, 36.6, 36.3, 31.9, 30.2,
29.9, 29.88, 29.85, 29.7, 29.4, 27.94, 27.89, 22.7, 18.8, 14.1 ppm; HRMS
(ESI): m/z: calcd for C99H143NO16 +H+ [M+H]+ 1603.04796; found:
1603.04673; IR (ATR): n¯ =2920, 2851, 1722, 1604, 1579, 1489, 1455, 1383,
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Received: July 4, 2007
Published online: November 19, 2007
Chem. Eur. J. 2008, 14, 1155 – 1163
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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