New fluorescent calix crown ethers, Part II: Synthesis and complex formation in solution and the solid state

Article abstract of DOI:10.1002/ejoc.200800569

New luminescent 1-aza-15-crown-5 ethers bearing a coumarin unit were synthesised leading to the cavitand-based calix crown ether 9. The solid-state structures of crown ethers 5 and 6 and the solid-state structures of the sodium and potassium iodide comple

Full text of DOI:10.1002/ejoc.200800569

FULL PAPER
DOI: 10.1002/ejoc.200800569
New Fluorescent Calix Crown Ethers, Part II: Synthesis and Complex
Formation in Solution and the Solid State
Ion Stoll,[a] Ralf Brodbeck,[b] Sebastian Wiegmann,[a] Jens Eberhard,[a] Silke Kerruth,[a]
Beate Neumann,[c] Hans-Georg Stammler,[c] and Jochen Mattay*[a]
Keywords: Crown compounds / Fluorescence spectroscopy / Host-guest systems / Cavitands / Supramolecular chemistry
New luminescent 1-aza-15-crown-5 ethers bearing a couma- hancement for the association constant of the sodium com-
rin unit were synthesised leading to the cavitand-based calix
crown ether 9. The solid-state structures of crown ethers 5
and 6 and the solid-state structures of the sodium and potas-
sium iodide complexes of crown ether 5 are presented. The
association constants for the complex formation with alkali
metal ions in methanol were determined. Only weak com-
plex was found (KNa = 1215 M M
–1, KK = 497 –1). Selected equi-
librium structures of the complexes of 9 were examined by
Kohn–Sham density functional calculations to give a detailed
understanding of the interplay between the two involved
building blocks. Based on these results, a sidewise cation
binding of the host 9 can be assumed. These complex geome-
tries are distinct from our findings in our previous work for a
larger crown ether attached to a cavitand.
plexes were formed (KNa = 286
M M
–1, KK = 392 –1). The aza-
15-crown-5 ether was attached by a methylene unit to a cavi-
tand to give the new fluorescent calix crown ether 9. The
association constants for the sodium and potassium com-
plexes in methanol were investigated as well, and an en-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
receptor. The resorcinol-based cavitand[5] is a sophisticated
host molecule and offers various functional groups to form
weak interactions for complex formation.[6] The association
constants of the complexes formed in solution are weak,
and the selectivity is not complete.[7] Nevertheless, the cavit-
and provides a lipophilic cavity and an oxygen crown at
the upper rim, which makes it a versatile supramolecule for
recognition phenomena and possibly even substrate interac-
tions, in particular, for extended supramolecules based on
the cavitand.[8] Given the properties of these two building
blocks (i.e. a crown ether and the cavitand), a modular ap-
proach to new receptor molecules is obvious.[9] In our pre-
vious work, we presented the combination of the cavitand
with a fluorescent 1-aza-21-crown-7 ether.[10] The binding
strength of selected alkali-metal-ion complexes was in-
creased by at least one order of magnitude by the attached
cavitand over that of the crown ether alone. Herein, we re-
port that DFT calculations of a container-like supramolec-
ule containing the cavitand and crown ether indicated coop-
erative binding interactions. In this work, we present the
synthesis of luminescent 1-aza-15-crown-5 ethers 5, 6, and
7. The crown ether 7 is attached to the cavitand to form the
corresponding calix crown ether 9. Complex formation with
alkali metal ions in solution and the solid state were investi-
gated. Kohn–Sham density functional (KS-DFT) calcula-
tions for different conformations of the calix crown ether
complexes are presented to illustrate the interplay of the
cavitand with a small crown ether.
Introduction
Recognition phenomena are essential in biological sys-
tems. Therefore, the preparation of receptors for molecular
recognition is one of the main pursuits in supramolecular
chemistry.[1] One route to molecular receptors is to mimic
natural receptor characteristics, but entirely artificial recep-
tors are also of broad interest. A fundamental requirement
of molecular receptors is the selective and strong binding
of substrate molecules. Chemical sensing is very meaningful
in the research of receptor interactions as well.[2] Crown
ethers and aza-crown ethers are mature units in this context
and possess selectivity and strong binding.[3] Furthermore,
a variety of crown ether sensory systems are established in
supramolecular chemistry.[4] Hence, crown ethers are ade-
quate foundations upon which to build an artificial sensory
[a] Organische Chemie I, Fakultät für Chemie, Universität Biele-
feld,
Postfach 100131, 33501 Bielefeld, Germany
Fax: +49-521-6417
E-mail: oc1jm@uni-bielefeld.de
[b] Theoretische Chemie, Fakultät für Chemie, Universität Biele-
feld,
Postfach 100131, 33501 Bielefeld, Germany
[c] Anorganische Chemie III, Universität Bielefeld,
Postfach 100131, 33501 Bielefeld, Germany
Fax: +49-521-6181
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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J. Mattay et al.
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diphenylmethane-protected crown ether 6 to allow for eas-
ier removal without an adverse effect to the coumarin
double bond. Unfortunately, none of the reported methods
worked properly in our hands. Also, deprotection by the
palladium-catalysed hydrogenation of 6 only progressed at
a reasonable rate if stoichiometric amounts of the catalyst
were used at higher temperatures (60 °C, Scheme 2).
Fortunately, no reaction occurred at the coumarin
double bond of 6 under palladium-catalysed hydrogenation
conditions even over very long reaction times (days). At this
time, we have no explanation for this result. The reaction
can be accelerated by the addition of hydrochloric acid, but
we were discouraged by this, because acid-catalysed cleav-
age of the coumarin lactone can emerge as a side reaction.
A disadvantage of the use of diphenylmethane as a pro-
Results and Discussion
The coumaryl crown ethers 5 and 6 were synthesised
analogously to the coumaryl N-benzylaza-21-crown-7 ether,
as reported previously.[10] 2-(2-Hydroxyethoxy)ethyl tolu-
ene-4-sulfonate 2 was attached to the dihydroxy coumarin
(1),[11] and the product was tosylated. Cyclisation by use
of a primary amine gave the corresponding crown ethers.
Na2CO3 was used as a template for the crown ether forma-
tion (instead of a mixture of potassium and caesium car-
bonate). Furthermore, the yield was increased by the use of
toluene (Scheme 1).[12]
The benzyl group can be removed by hydrogenation, as
described previously.[10] We found that besides the cleavage
of the benzyl group, hydrogenation of the coumarin double
bond can also occur, although the double bond hydrogena- tecting group is that nonvolatile components are formed,
tion is slower than the removal of the benzyl group. It is and column chromatography is needed for the isolation of
difficult to achieve complete conversion to the deprotected the aza-crown ether. In the next step, the aza-crown ether 7
crown ether 7 without hydrogenation byproducts. The cata- was attached to the monobenzyl-bromo cavitand 8[10] by a
lytic removal of the benzyl group is a fast reaction, but the nucleophilic substitution leading to the cavitand-based calix
reaction rate is also very sensitive to the amount of catalyst crown ether 9 (Scheme 3). The reaction was monitored by
and solvent. Some non-hydrogenation methods for the re- MALDI-ToF, and complete conversion was reached after
moval of a diphenylmethane group as protecting group for 2 h. A 60% isolated yield was achieved following column
an amine are reported.[13–16] Therefore, we synthesised the chromatography.
Scheme 1. Synthesis of the luminescent crown ethers 5 and 6. a) 2-(2-Hydroxyethoxy)ethyl toluene-4-sulfonate, K2CO3, DMF, 58%; b)
TsCl, iPr2EtN, CH2Cl2, 55%; c) Na2CO3, benzylamine, toluene, reflux 47%; d) Na2CO3, aminodiphenylmethane, toluene, reflux, 86%.
R = HOCH2CH2OCH2CH2.
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New Fluorescent Calix Crown Ethers
Scheme 2. Removal of the protecting group. a) H2, Pd/C (10%), EtOH, 50%.
Scheme 3. Synthesis of luminescent calix crown ether 9. a) Cs2CO3, DMF, 60%. R = C11H23.
Single crystals of crown ethers 5 and 6 were grown from by slow concentration. In accordance with the estimated
saturated ethanol solutions. The solid-state structures are complex stoichiometry in methanol solution (see below),
shown in Figures 1 and 2. In both crystal structures no sol- crown ether 5 forms a 1:1 complex with sodium iodide in
vent molecules are included. Crystallographic details are the solid state (Figure 3).
given in the Experimental Section.
Figure 1. Solid-state structure of luminescent crown ether 5. Hy-
drogen atoms are omitted.
Figure 3. Sodium iodide complex of crown ether 5. Hydrogen
atoms are omitted. Two ethanol molecules are incorporated (upper
sphere).
In solution, only poor association constants were found
for the sodium complex of 5 and related N-benzylaza-15-
crown-5 ethers.[3,17–20] A stronger binding of sodium ions
by N-substituted aza-15-crown-5 ethers is reported if six
oxygen atoms beside the nitrogen atom are present for bind-
ing.[21,22] This is in agreement with our findings in the solid
state. Two solvent molecules (ethanol) were incorporated
Figure 2. Solid-state structure of luminescent crown ether 6. Hy-
drogen atoms are omitted.
Crystal structures of the potassium and sodium iodide into the complex to increase the coordination number of
complexes of crown ether 5 were also obtained. They were the sodium ion. The coordination number is seven, includ-
grown from the metal-salt-saturated ethanol solution of 5 ing the crown ether nitrogen atom.
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The longest oxygen–sodium contacts are from the crown
ether oxygens attached to the coumarin (d = 2.772 and
2.561 Å). Only one is suitable for a close contact, probably
by the avoided rotation due to the integrated coumarin. The
nitrogen–sodium (d = 2.606 Å) distance is longer than the
remaining crown oxygen–metal distances and the solvent–
metal distances (d = 2.375–2.514 Å). The counterion
(iodide) is far separated from the metal ion
[d(I–Na) = 5.179 Å]. In the literature, only weak binding of
N-benzylaza-15-crown-5 ethers with potassium ions is re-
ported. Solid-state structures of potassium complexes of re-
lated compounds show (1:1)n, (2:2)n, and solvent-mediated
2:2 complexes rather than 1:1 stoichiometries.[17–20] The X-
ray structure of the potassium complexes of crown ether 5
showed an isolated 2:2 complex (Figure 4).
Figure 5. Absorption (–) and emission (···) spectra of luminescent
crown ether 5 in methanol (c = 1ϫ10–5 , λex = 317 nm).
Figure 4. 2:2 complex of potassium iodide and crown ether 5. Hy-
drogen atoms are omitted. One ethanol molecule is incorporated.
Interestingly, the shortest metal–oxygen contact in the
potassium iodide structure is from the carbonyl oxygen
atom of the coumarin unit to the neighbouring metal centre
(d = 2.753 Å). One coumarin oxygen atom is more closely
coordinated than the second (d = 2.779 and 2.916 Å), as
was observed in the sodium complex. The nitrogen atom
takes part in the metal ion coordination, but one solvent
molecule is still incorporated to increase the coordination
sphere. In contrast to the sodium complex of 5, the counter-
ion is not far separated [d(I–K) = 3.652 Å].
The absorption and emission spectra of crown ether 5
are presented in Figure 5. The absorbance spectrum shows
the typical absorption of a 7,8-substituted coumarin
unit.[23,24] A local maximum of absorption at 318 nm and a
smaller one at 255 nm was found, whereas the maximum
of absorption in the aromatic region was at 205 nm. The
fluorescence maximum was observed at 451 nm.
Figure 6. Absorption (–) and emission (···) spectra of luminescent
calix crown ether 9 in methanol (c = 1ϫ10–5 , λex = 317 nm).
sion significantly. The crown ether 5 and the calix crown
ether 9 were titrated with solutions of different alkali-metal
acetates to obtain association constants for complex forma-
tion by nonlinear curve fitting.[10] The determined associa-
tion constants are shown in Table 1. For all titration plots,
the coefficient of determination was higher than 0.99. All
fluorescence spectra, titration plots, and Job plots are given
in the Supporting Information. As mentioned above, only
weak complexes of N-benzylaza-15-crown-5 ethers and al-
kali metal ions are formed.[21,22]
The absorption and emission spectra of calix crown ether
9 are shown in Figure 6. The maximum emission is slightly
blueshifted compared to that of 5 (448 nm). In the absorp-
tion spectrum, a superposition of the coumarin absorbance
and the absorbance of the resorcarene arenes was observed
with two maxima at 317 nm and 277 nm.
The maximum absorbance in the aromatic region is at
204 nm. The absorption and emission spectra of com-
pounds 6 and 7 are given in the Supporting Information.
Cation addition changed the emission spectra of 5 and 9
Table 1. Association constants of 5 and 9 in methanol with alkali-
metal acetates at 25 °C.
Entry
Compound
Guest
K [–1]
log(K/[–1])
1
2
3
4
9
Na+
1215Ϯ168
497Ϯ33
268Ϯ26
392Ϯ75
3.08
2.70
2.43
2.59
K+
5
Na+
K+
This was also found for crown ether 5. The association
owing to the change of the excited-state dipole of the com- constant of the potassium complex of 5 exceeded that of
plexes formed (photoinduced charge transfer, PCT).[10,25]
A
the sodium complex, but no pronounced selectivity was
photoinduced electron-transfer mechanism from the crown found. For both complexes, a 1:1 stoichiometry in solution
ether nitrogen atom can be ruled out, because titration of can be estimated by the shape of the binding isotherm, and
the hosts with trifluoroacetic acid does not change the emis- the stoichiometry was confirmed by a Job-plot analysis.[26]
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New Fluorescent Calix Crown Ethers
Even though we found a 2:2 complex of potassium and 5 stick representation of the equilibrium structures obtained
in the solid state, we exclude the formation of a 2:2 complex with a sidewise arrangement. Cartesian coordinates and
in solution. A 2:2 complex is not distinguishable from a 1:1 electronic energies are given in the Supporting Information.
complex by a Job-plot analysis, but the involvement of the
carbonyl oxygen atom and the resulting change in the elec-
tronic environment by complexation would change the pho-
tochemical properties of the formed complex dramatically.
Therefore, we assume that no 2:2 complexes with participa-
tion of the carboxylic oxygen in complexation were formed.
An additional argument against the appearance of a 2:2
complex in solution is the high dilution of the sample solu-
tion (1ϫ10–5 ). For the alkali-metal complexes of 9, a
preference for sodium ions was found. The association con-
stant was almost five times as large as that for the sodium
complex of 5. The association constant for the potassium
complex of 9 was only marginally larger than that of the
potassium complex of 5. In summary, the strength of the
potassium complexes of hosts 5 and 9 and the sodium com-
plex of host 5 were low, and no distinct preference was
found. Only the sodium complex of host 9 was favoured.
The strength of the formed complexes of N-pivot crown Figure 7. Calculated structures for the sidewise conformer of the
potassium (top) and sodium (bottom) complex of 9. Hydrogen
atoms are omitted.
ethers is mainly influenced by the number of oxygen atoms
involved in the complexes.[12,21] By attaching the cavitand,
the number of oxygen atoms for complexation is only in-
creased by one (see below). From the solid-state structures
For both cations (from each starting geometry), a local
of the crown ether moiety (see above), it can be established minimum was found: one with a complexation with a sand-
that three crown oxygen atoms can develop short metal ion wich-like geometry and one sidewise to the resorcarene. For
contacts. Hence, the calix crown ether 9 provides only a both cations, the sidewise conformer was energetically
small coordination sphere. This is in good agreement with strongly favoured. Therefore, we assume that the sidewise
a preferential binding for sodium ions. We assume that this conformer displays the global minimum in the gas phase.
small coordination sphere is not able to stabilise the potas-
For the potassium complex, the sandwich conformer was
sium complex in a distinct manner. Titration experiments 69 kJ/mol higher in energy than the sidewise conformer.
with lithium acetate were carried out as well. Regrettably, The stabilisation in the sidewise isomer occurs because
no association constants were obtained within an accept- shorter metal–oxygen contacts are achievable, and thereby
able experimental error. As already mentioned, the change an increased coordination number is also possible. The co-
in the excited-state dipole of a complex accounts for ordination number was six (including a K–N contact), and
changes in emission spectra. The magnitude of this change the K–O distances range from 273 to 283 pm [d(K–N) =
is specific for the guest cation. For the lithium complexes 291 pm]. The sidewise-complexation isomer was also fav-
of 5 and 9, the change was very small, leading to a large oured over the sandwich conformer by 75 kJ/mol for the
experimental error. Nevertheless, a 1:1 complex stoichiome- sodium complex. Shorter metal–oxygen distances [233–
try for the lithium complexes of 5 and 9 were assured by 246 pm, d(Na–N) = 250 pm] were found for the sidewise
Job plots.
conformation than were found for the sandwich conformer
As previously reported, the combination of a larger [239–249 pm, d(Na–N)
=
248 pm]. The coordination
crown ether and the cavitand can enhance the association number of the sidewise conformer was six. For the sand-
constants for complex formation with alkali-metal acetates wich conformer, the coordination number was five, but one
in a synergistic manner.[10] To evaluate the interplay of the short contact (279 pm) to a methylene hydrogen atom of
two building blocks, we examined the sodium and the po- the cavitand was also found.
tassium complexes of 9 by structure optimisation and nor-
In conclusion, the sidewise conformation was strongly
mal-mode analysis in the framework of KS-DFT (for de- preferred in the gas phase for both cations due to the in-
tails see the Experimental Section). Two different starting creased coordination number and the smaller metal–oxygen
structures were taken into account for each guest cation: a distances. Additionally, solid-state structures were exam-
sandwich-like arrangement of the two host building blocks ined, and the methylene units of the cavitand were pointing
and an arrangement with the metal-cation-containing aza- out of the cavity. Sandwich and sidewise conformers were
crown ether rotated away from the calixarene moiety (side- calculated, and two local minima for each cation were
wise conformation). The starting geometries of the crown found and confirmed by normal-mode analysis. All of these
ether moiety were taken from the X-ray structures. For the minima were remarkably higher in energy than the minima
calculations, the resorcarene lower-rim n-undecyl chains described above. The calculated structures and energies are
were replaced by methyl groups. Figure 7 shows a ball-and- given in the Supporting Information.
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J. Mattay et al.
FULL PAPER
of equilibrium structures consistently to 10–7 a.u. (the same accu-
racy as for the electronic energy). Harmonic vibrational wave-
numbers were obtained from analytic second derivatives of the en-
ergy.
Conclusions
We have presented the synthesis of three new fluorescent
15-crown-5 ethers (5–7) and a fluorescent calix crown ether
(9). The absorption and emission properties of these com-
pounds were also characterised. The solid-state structures
of 5 and 6 were presented as well as the solid-state struc-
tures of the potassium and sodium iodide complexes of 5.
For the potassium complex, we found that the coumaryl
carboxyl oxygen atom participated in the formation of a 2:2
complex. The association constants and the stoichiometries
for complex formation in methanol of hosts 5 and 9 with
sodium and potassium acetate were determined. Host 5
formed only weak complexes. Moreover, the potassium
complex of 9 was also weak. For the sodium complex of 9,
an association constant almost five times larger than that
for 5 was found, which showed that the interplay of the
cavitand and the crown ether was stabilising. The contri-
bution of the attached resorcarene in complex formation
was investigated by KS-DFT calculations. Herein, we have
shown that a sidewise-like complex conformation was fav-
oured for both cations.
2-(2-Hydroxyethoxy)ethyl Toluene-4-sulfonate (2): To a solution of
diethylene glycol (66.88 g, 630 mmol) and triethylamine (32.77 g,
324 mmol) in dichloromethane (150 mL), p-toluenesulfonyl chlo-
ride (30.61 g, 161 mmol) was added in portions at 0 °C. The solu-
tion was stirred at this temperature for 2 h. The organic layer was
washed with saturated aqueous NaHCO3 solution and dried with
anhydrous MgSO4. After evaporation of the solvent, the crude
product was purified by flash column chromatography (SiO2,
dichloromethane/methanol, 98:2) to yield a colourless oil (23.59 g,
1
91 mmol, 56%). H NMR (CDCl3, 500 MHz, 27 °C): δ = 7.78 (d,
3J = 8.2 Hz, 2 H, ArH), 7.33 (d, 3J = 8.2 Hz, 2 H, ArH), 4.17
(t, 3J = 5.2 Hz, 2 H, OCH2CH2OTs), 3.67 (t, 3J = 5.2 Hz, 2 H,
3
OCH2CH2OTs), 3.64 (t, J = 5.2 Hz, 2 H, OCH2CH2OH), 3.51 (t,
3J = 4.4 Hz, 2 H, OCH2CH2OH), 2.42 (s, 3 H, CH3), 1.95 (s, 1 H,
OH) ppm.
7,8-Bis[2-(2-hydroxyethoxy)ethoxy]-4-methyl-2H-chromen-2-one (3):
K2CO3 (12.54 g, 91 mmol) was suspended in a solution of 7,8-dihy-
droxy-4-methylcoumarin (1, 7.92 g, 41 mmol) and tosylated glycol
2 (23.56 g, 91 mmol) in N,N-dimethylformamide (200 mL). The
solution was stirred under argon at 80 °C for 20 h. The solvent was
removed in vacuo, and the residue was dissolved in water (400 mL).
The pH was adjusted to 3 with dilute HCl. The aqueous phase was
extracted with dichloromethane (6ϫ130 mL), and the combined
organic phases were dried with anhydrous MgSO4. After evapora-
tion of the solvent, the crude product was purified by flash column
chromatography (Al2O3, dichloromethane/diethyl ether/ethanol,
6:6:1) to give a yellowish oil (8.76 g, 24 mmol, 58%). 1H NMR
(CDCl3, 500 MHz, 27 °C): δ = 7.25 (d, 3J = 8.8 Hz, 1 H, ArH),
6.85 (d, 3J = 8.8 Hz, 1 H, ArH), 6.11 (s, 1 H, C=CH), 4.23–4.28
(m, 4 H, OCH2CH2O), 3.87–3.89 (m, 2 H, OCH2CH2O), 3.83–3.84
(m, 2 H, OCH2CH2O), 3.69–3.71 (m, 4 H, OCH2CH2OH), 3.63–
Experimental Section
General Procedure for Fluorescence Titrations: A solution of the
host was prepared in methanol (c = 1.0ϫ10–5 ). 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 10ϫ4 mm half-micro quartz
cuvette from Hellma. When not in use the cuvette was stored in
Caro’s acid. Spectra were recorded five times and accumulated.
Subsequently, small amounts of alkali-metal acetate (sodium and
potassium acetate 99%, Merck) solutions in methanol (1- and 5-
µL steps of a 0.5  solution) were added. This led to a host/guest
ratio ranging from 1:50 to at least 1:1850 at saturation concentra-
tion. The cuvette was shaken for 1 min and was allowed to equili-
brate for an additional 1 min. After each addition, spectra were
recorded until complex saturation was reached. Care was taken to
increase the reaction volume Ͻ6%. The excitation wavelength was
317 nm, and the monochromator bandwidth was set to 6 nm for
the excitation and emission monochromator for host 9 and to 7 nm
for the excitation and emission monochromator for host 5. All
spectra were recorded with a Perkin–Elmer LS50B luminescence
spectrometer and a Perkin–Elmer Lambda 40 UV/Vis spectrome-
ter. Integrated fluorescence intensities were used for analysis. Inte-
grations were carried out with the software SPEKWIN32[27] from
the isoemissive point to the baseline (610 nm). This approach was
used for the sake of precision caused by the slight blueshift.
3
3.65 (m, 4 H, OCH2CH2OH), 3.45 (t, J = 6.3 Hz, 1 H, OH), 3.28
(t, 3J = 6.3 Hz, 1 H, OH), 2.35 (s, 3 H, CH3) ppm. 13C NMR
(CDCl3, 125 MHz, 27 °C): δ = 160.6, 154.5, 152.6, 147.8, 135.5,
119.6, 115.1, 112.4, 109.8, 73.0, 72.8, 72.6, 70.2, 69.2, 68.9, 61.6,
61.5, 18.7 ppm. HRMS (ESI): m/z calcd. for C18H24O8 [M + H]+
369.15439; found 369.15495. IR (ATR): ν = 3235, 3113, 3087, 2953,
˜
2933, 2882, 2828, 1716, 1605, 1564, 1506, 1472, 1446, 1433, 1387,
1372, 1315, 1296, 1255, 1245, 1222, 1182, 1138, 1101, 1033, 1020,
997, 935, 904, 881, 858, 847, 841, 905, 785, 775, 722, 716, 663, 651,
607, 579, 589, 531 cm–1.
7,8-Bis{2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy}-4-methyl-2H-chromen-
2-one (4): A solution of chromenone 3 (8.27 g, 22 mmol) and ethyl-
diisopropylamine (8.71 mL, 67 mmol) in dichloromethane
(100 mL) was cooled to 0 °C. p-Toluenesulfonyl chloride (12.84 g,
67 mmol) was added rapidly in portions, and the mixture was
stirred at room temperature for 48 h. Additional ethyldiisopropyl-
amine (8.71 mL, 67 mmol) and p-toluenesulfonyl chloride (12.84 g,
67 mmol) were added at 0 °C, and the mixture was stirred at room
temperature for 3 d. Water (100 mL) was added, and the pH was
adjusted to 3 with dilute HCl. The aqueous phase was extracted
with dichloromethane (3 ϫ 50 mL), and the combined organic
phases were washed with saturated aqueous NaHCO3 solution and
dried with anhydrous MgSO4. The crude product was purified by
flash column chromatography [(i) SiO2, dichloromethane/meth-
anol, 100:0 Ǟ 99:1 Ǟ 98:2 and (ii) Al2O3, dichloromethane/meth-
anol, 99:1] to give a yellowish oil (8.23 g, 12.2 mmol, 55%).1H
NMR (CDCl3, 500 MHz, 27 °C): δ = 7.70–7.73 (m, 4 H, ArH),
Details of Calculations: All calculations reported herein were per-
formed with the TURBOMOLE[28] programme suite. We choose
the BP86 functional [includes B88[29] gradient correction for ex-
change, the VWN-(V)[30] correlation functional, and the P86[31] gra-
dient correction for correlation] combined with the TZVP basis
set (triple-zeta quality, polarized for all centres). To speed up the
calculations, the charge-density fitting approximation[32] was used,
with the auxiliary basis sets[32] from the programmes basis set data-
base. For the structure optimizations and normal-mode analyses,
we choose the grid-type “m5”. In the structure optimizations, the
threshold for energy changes (10–7 a.u.) and changes of the root-
mean-square of the gradient (10–3 a.u.) were chosen to give energies
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New Fluorescent Calix Crown Ethers
3
7.22–7.27 (m, 5 H, ArH), 6.84 (d, J = 8.8 Hz, 1 H, ArH), 6.09 (s,
6 (72 mg, 0.14 mmol) in ethanol (40 mL), Pd/C (10%, 68 mg) was
1 H, C=CH), 4.08–4.16 (m, 8 H, OCH2CH2O), 3.70–3.81 (m, 8 H, added. Hydrogen was discharged into the solution for 25 min, and
OCH2CH2O), 2.37 (s, 6 H, CH3), 2.34 (s, 3 H, CH3) ppm. 13C
the solution was heated to 60 °C for 2 h. The reaction was moni-
NMR (CDCl3, 125 MHz, 27 °C): δ = 160.5, 154.5, 152.6, tored by MALDI-ToF. After complete conversion, the catalyst was
144.8,144.7, 135.6, 132.8, 129.8, 127.9, 119.6, 112.4, 109.8, 72.9,
70.6, 69.6, 69.5, 69.3, 68.9, 68.8, 68.6, 43.0, 21.6, 18.7 ppm. HRMS
filtered off, and the solvent was removed in vacuo. The crude prod-
uct was filtered through basic alumina (CHCl3/MeOH, 1:1) and
(ESI): m/z calcd. for C32H36O12S2 [M + H]+ 677.17209; found purified by flash column chromatography (Al2O3, CHCl3/MeOH,
677.17162. IR (ATR): ν = 3090, 3064, 2946, 2924, 2873, 2363, 2328,
98:2) to give a colourless solid (25 mg, 0.07 mmol, 50%). 1H NMR
˜
1723, 1601, 1563, 1507, 1448, 1384, 1352, 1296, 1244, 1174, 1136,
(CDCl3, 500 MHz, 27 °C): δ = 7.24 (d, 3J = 8.8 Hz, 1 H, ArH),
1094, 1038, 1016, 964, 919, 815, 772, 705, 690, 663, 582, 554 cm–1.
6.84 (d, J = 8.8 Hz, 1 H, ArH), 6.11 (s, 1 H, C=CH), 4.33 (t, J
= 3.8 Hz, 2 H, OCH2CH2O), 4.17 (t, 3J = 3.8 Hz, 2 H, OCH2-
CH2O), 3.88 (t, 3J = 4.1 Hz, 2 H, OCH2CH2O), 3.78 (t, 3J =
4.1 Hz, 2 H, OCH2CH2O), 3.73 (t, 3J = 4.7 Hz, 2 H, OCH2CH2O),
3.67 (t, 3J = 4.7 Hz, 2 H, OCH2CH2O), 2.88–2.80 (m, 4 H, NCH2),
2.36 (s, 3 H, CH3) ppm. 13C NMR (CDCl3, 125 MHz, 27 °C): δ =
160.7, 154.7, 152.8, 148.0, 135.0, 119.4, 114.7, 112.2, 108.3, 73.2,
69.8, 69.6, 68.5, 68.2, 68.1, 48.3, 47.8, 18.8 ppm. HRMS (ESI): m/z
calcd. for C18H24NO6 [M + H]+ 350.15981; found 350.15959. IR
3
3
7-Benzyl-16-methyl-2,3,5,6,8,9,11,12-octahydrochromeno[7,8-b]-
[1,4,10,13,7]tetraoxaazacyclopentadecin-18-one (5): In a solution of
chromenone 4 (1.02 g, 150 mmol) and benzylamine (0.16 g,
150 mmol) in toluene (150 mL), Na2CO3 (1.59 g, 14.99 mmol) was
suspended. The mixture was refluxed under argon for 6 d. The re-
action mixture was cooled to room temperature, and the solid was
filtered off. Methanol (4 mL) was added to the filtrate, and the
mixture was stirred at 50 °C for 40 min. The solvent was evaporated
in vacuo, and the crude product was purified by column
chromatography (Al2O3, ethyl acetate/cyclohexane, 45:55) to give a
colourless solid (0.31 g, 0.7 mmol, 47%). The crown ether can be
recrystallised from ethanol. 1H NMR (CDCl3, 500 MHz, 27 °C): δ
(ATR): ν = 3317, 2926, 2871, 1728, 1604, 1508, 1449, 1385, 1298,
˜
1098 cm–1.
Cavitand 9: A mixture of aza-crown ether 7 (18 mg, 0.05 mmol),
cavitand 8[10] (76 mg, 0.06 mmol) and Cs2CO3 (43 mg, 0.13 mmol)
in dry N,N-dimethylformamide (6 mL) was stirred under argon at
80 °C for 2 h. The solvent was removed in vacuo, and the precipi-
tate was dissolved in chloroform and washed with water. The aque-
ous phase was extracted twice with chloroform, and the combined
organic phases were concentrated. The crude product was purified
by flash column chromatography (Al2O3, CHCl3/MeOH, 99:1) to
give the calix crown ether as a colourless solid (45 mg, 0.03 mmol,
60%). 1H NMR (CDCl3, 500 MHz, 27 °C): δ = 7.26 (d, 3J =
8.8 Hz, 1 H, ArH, coumarin), 7.09 (s, 3 H, ArH), 7.04 (s, 1 H,
ArH), 6.83 (d, 3J = 8.8 Hz, 1 H, ArH, coumarin), 6.46 (s, 1 H,
3
= 7.17–7.25 (m, 6 H, ArH), 6.83 (d, J = 8.8 Hz, 1 H, ArH), 6.10
(s, 1 H, C=CH), 4.28 (m, 2 H, OCH2CH2O), 4.18 (m, 2 H, OCH2-
CH2O), 3.91 (m, 2 H, OCH2CH2O), 3.83 (m, 2 H, OCH2CH2O),
3.72 (m, 2 H, OCH2CH2O), 3.69 (m, 2 H, OCH2CH2O), 3.66 (s, 2
H, PhCH2), 2.80–2.83 (m, 4 H, NCH2), 2.35 (s, 3 H, CH3) ppm.
13C NMR (CDCl3, 125 MHz, 27 °C): δ = 160.6, 155.0, 152.6, 148.0,
139.3, 135.2, 128.8, 128.1, 126.8, 119.5, 114.7, 112.2, 108.6, 73.1,
70.4, 70.1, 69.4, 69.0, 68.9, 60.6, 54.1, 53.9, 29.2, 18.7 ppm. HRMS
(ESI): m/z calcd. for C25H29NO6 [M + H]+ 440.20676; found
440.20660. IR (ATR): ν = 3084, 3061, 3026, 2961, 2867, 2247, 1725,
˜
3
ArH), 6.43 (s, 2 H, ArH), 6.12 (s, 1 H, CH, coumarin), 5.80 (d, J
1646, 1604, 1562, 1507, 1495, 1448, 1439, 1384, 1367, 1360, 1297,
1241, 1203, 1177, 1129, 1096, 1045, 1028, 962, 911, 871, 849, 801,
772, 730, 699, 664, 646, 554 cm–1.
3
= 7.5 Hz, 2 H, OCH2O), 5.72 (d, J = 7.5 Hz, 2 H, OCH2O), 4.70
(t, 3J = 8.2 Hz, 4 H, ArCHAr), 4.43 (d, 3J = 6.9 Hz, 2 H, OCH2O),
4.30 (d, 3J = 6.9 Hz, 2 H, OCH2O), 4.29 (t, 3J = 4.6 Hz, 2 H,
3
3
7-(Diphenylmethyl)-16-methyl-2,3,5,6,8,9,11,12-octahydrochromeno-
[7,8-b][1,4,10,13,7]tetraoxaazacyclopentadecin-18-one (6): To a solu-
tion of chromenone 4 (1.02 g, 1.51 mmol) and aminodiphenylme-
thane (0.3 g, 1.64 mmol) in toluene (150 mL), Na2CO3 (1.6 g,
151 mmol) was added. The mixture was refluxed for 8 d, and ad-
ditional aminodiphenylmethane (0.16 g, 0.87 mmol) was added.
The mixture was refluxed for 2 d, and the solid was filtered of.
The filtrate was concentrated in vacuo, and the crude product was
purified by flash column chromatography (SiO2, ethyl acetate/
cyclohexane 7:3) to give a colourless solid (667 mg, 1.29 mmol,
86 %). The crown ether can be recrystallised from ethanol. 1H
NMR (CDCl3, 500 MHz, 27 °C): δ = 7.11–7.43 (m, 11 H, ArH),
OCH2CH2O), 4.17 (t, J = 3.8 Hz, 2 H, OCH2CH2O), 3.89 (t, J
= 3.5 Hz, 2 H, OCH2CH2O), 3.82 (t, 3J = 4.1 Hz, 2 H, OCH2-
CH2O), 3.73 (t, J = 5.4, 4 H, OCH2CH2O), 3.47 (s, 2 H, ArCH2),
3
2.84–2.74 (m, 4 H, NCH2CH2), 2.36 (s, 3 H, CH3, coumarin), 2.28–
2.08 (m, 8 H, CHCH2), 1.48–1.16 (m, 72 H, CH2), 0.86 (t, 3J =
6.9 Hz, 12 H, CH3) ppm. 13C NMR (CDCl3, 125 MHz, 27 °C): δ
= 160.6, 155.0, 1554.8, 154.7, 154.3, 152.6, 148.0, 138.4, 138.3,
138.1, 138.0, 135.2, 123.7, 120.6, 120.5, 119.7, 119.6, 116.5, 116.3,
114.8, 112.3, 108.6, 99.6, 99.5, 73.1, 70.2, 69.8, 69.0, 68.8, 53.0,
52.9, 48.6, 36.6, 36.3, 31.9, 30.1, 29.9, 29.8, 29.7, 29.4, 27.9, 27.87,
22.7, 18.8, 14.1 ppm. HRMS (ESI): m/z calcd. for C95H135NO14 [M
+ H]+ 1514.99553; found 1514.99984. IR (ATR): ν = 2920, 2851,
˜
3
1724, 1605, 1491, 1456, 1296, 1094, 1020, 965 cm–1.
6.84 (d, J = 8.8 Hz, 1 H, ArH), 6.12 (s, 1 H, C=CH), 4.80 (s, 1 H,
3
3
Bnz), 4.29 (dd, J = 4.4 Hz, J = 4.4 Hz, 2 H, OCH2CH2O), 4.17
Crystal Structure Determination: CCDC-681208, -681209, -681210
and -681211 contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif. Crystal Data for 5: C25H29NO6, M = 439.49, tri-
clinic, a = 8.6458(2), b = 9.2239(2), c = 14.9930(3) Å, α =
(dd, 3J = 3.8 Hz, 3J = 3.8 Hz, 2 H, OCH2CH2O), 3.86 (dd, 3J =
3
3
3
4.4 Hz, J = 4.4 Hz, 2 H, OCH2CH2O), 3.78 (dd, J = 3.8 Hz, J
= 3.8 Hz, 2 H, OCH2CH2O), 3.74 (t, 3J = 5.6 Hz, 2 H, OCH2-
CH2O), 3.64 (t, 3J = 6.1 Hz, 2 H, OCH2CH2O), 2.80–2.90 (m, 4
H, NCH2), 2.36 (s, 3 H, CH3) ppm. 13C NMR (CDCl3, 125 MHz,
27 °C): δ = 160.7, 155.0, 152.7, 148.0, 142.6, 135.2, 128.4, 128.3,
126.9, 119.5, 114.8, 112.3, 108.7, 73.1, 71.3, 70.2, 70.0, 69.3, 69.0,
52.2, 52.0, 18.7 ppm. HRMS (ESI): m/z calcd. for C31H33NO6 [M
85.0614(11), β = 79.7561(12), γ = 73.8471(12)°, V = 1129.31(4) Å3,
–1
¯
T = 200 K, space group P1, Z = 2, µ(Mo-Kα) = 0.092 mm , 28810
reflections measured, 5152 unique (Rint = 0.030), which were used
in all calculations. The final R values were R(F) = 0.0439 for 4181
reflections with I Ͼ 2σI and wR(F2) = 0.1250 for all data. Crystal
Data for the NaI Complex of 5: C29H41INNaO8, M = 681.52, tri-
clinic, a = 10.2040(9), b = 11.2107(4), c = 15.6238(9) Å, α =
69.016(4), β = 81.114(6), γ = 67.451(5)°, V = 1540.86(17) Å3, T =
+ H]+ 516.23806; found 516.23808. IR (ATR): ν = 3024, 2925,
˜
2865, 1724, 1602, 1562, 1502, 1448, 1383, 1295, 1240, 1126, 1093,
1024, 907, 850, 727, 705 cm–1.
16-Methyl-2,3,5,6,8,9,11,12-octahydrochromeno[7,8-b][1,4,10,13,7]-
tetraoxaazacyclopentadecin-18-one (7): Tο a solution of crown ether
Eur. J. Org. Chem. 2008, 5231–5238
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5237

J. Mattay et al.
FULL PAPER
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reflections measured, 7086 unique (Rint = 0.0529), which were used
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0.035), which were used in all calculations. The final R values were
R(F) = 0.0418 for 7143 reflections with I Ͼ 2σI and wR(F2) =
0.1029 for all data. Crystal Data for 6: C31H33NO6, M = 515.58,
triclinic, a = 9.1103(3), b = 10.5503(3), c = 14.7398(4) Å, α =
80.423(2), β = 75.997(2), γ = 84.560(2)°, V = 1353.27(7) Å3, T =
–1
¯
200 K, space group P1, Z = 2, µ(Mo-Kα) = 0.087 mm , 26984
reflections measured, 4748 unique (Rint = 0.055), which were used
in all calculations. The final R values were R(F) = 0.0672 for 3240
reflections with I Ͼ 2σI and wR(F2) = 0.2135 for all data.
Supporting Information (see also the footnote on the first page of
this article): Absorption and emission spectra of compounds 6 and
7, all titration plots, Job plots, and cartesian coordinates for all
calculated structures.
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Received: June 11, 2008
Published Online: September 22, 2008
5238
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5231–5238