Photo, proton and metal ion responsive wide-rim acridane substituted calix[4]arenes

Article abstract of DOI:10.1016/j.tet.2009.05.082

Calix[4]arenes bearing acridinium and acridane substituents at the wide rim and a short glycol chain and two OH-groups at the narrow rim have been prepared. The interaction with alkali metal ions can be identified with the naked eye by the change in solution color arising from deprotonation of the OH-groups. Unlike the acridane calixarenes, the acridinium-substituted calixarene-crown-4 binds sodium ions. Due to the photoheterolysis of the acridane, calixarene sodium ions are picked up from the acetonitrile solution due to the formation of acridinium calixarene.

Full text of DOI:10.1016/j.tet.2009.05.082

Tetrahedron 65 (2009) 5936–5944
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Photo, proton and metal ion responsive wide-rim acridane substituted
calix[4]arenes
*
L. Grubert, H. Hennig, W. Abraham
Humboldt-Universita¨t zu Berlin, Institute of Chemistry, Brook-Taylor-Str. 2, 12489 Berlin, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 May 2009
Received in revised form 26 May 2009
Accepted 28 May 2009
Available online 6 June 2009
Calix[4]arenes bearing acridinium and acridane substituents at the wide rim and a short glycol chain and
two OH-groups at the narrow rim have been prepared. The interaction with alkali metal ions can be
identified with the naked eye by the change in solution color arising from deprotonation of the OH-
groups. Unlike the acridane calixarenes, the acridinium-substituted calixarene-crown-4 binds sodium
ions. Due to the photoheterolysis of the acridane, calixarene sodium ions are picked up from the ace-
tonitrile solution due to the formation of acridinium calixarene.
Keywords:
Calixarene
Ó 2009 Elsevier Ltd. All rights reserved.
Acridinium salt
Acridanes
Photoswitch
Cation receptor
1. Introduction
Earlier investigations have shown that calix[4]arenes with four
alkyloxy substituents at the narrower rim are not able to complex
Calixarenes1 belong to the important category of building blocks
for supramolecular assemblies2 and molecular recognition, and are
widely used as receptors for inorganic and organic cations,3,4 an-
ions,5 and also neutral compounds.6 endo-Cavity inclusion com-
plexes with organic cations such as quaternary ammonium ions
and the iminium and tropylium ions are assumed to be favored by
organic cations,7 and therefore we sought to obtain calix[4]arenes
with two alkoxy and two hydroxyl groups at the narrower rim.
Herein, we report the synthesis and conformation of calix[4]arenes
substituted at the wider rim with acridane and acridinium units
and OH-groups at the same aryl units. We also present calix[4]-
arenes with a short glycol bridge exhibiting a cone conformation.
The p-hydroxyphenylacridinium subunit within the calixarene
framework offers the possibility of color changes by deprotonation
of the OH-groups due to the presence of a quinonoid structure. We
examined the influence of bases on this process and also performed
photochemical experiments to explore the reversibility of the
switching process. We also present some complexation results.
cation-p-interaction and p
-stacking.7
The introduction of switches into the calixarenes has attracted
interest as a means of obtaining gated hosts.8,9 A photoswitchable
resorc[4]arene based on [4þ4]cycloaddition of anthracene has been
studied recently with the aid of single-molecule force spectros-
copy.10 We became interested in introducing a photoswitch into
calix[4]arenes that reversibly switches between electron deficient
and electron rich groups. The system 9-alkoxy acridane (9,10-dihy-
droacridine), which undergoes photoheterolysis in the photoexcited
state to give an acridinium salt, matches these requirements.11 The
reset of the system proceeds in protic solvents by attack of the alk-
oxide on the acridinium ion.11 Recently, we have synthesized
calix[4]arenes with such substituents having a 1,3-alternate con-
formation and glycol bridges at the aryl units, which carry the
switching unit.11 Additionally we described calix[4]arenes with
four alkylated OH-groups having a pinched-cone conformation.11
2. Results and discussion
2.1. Synthesis
In contrast to results obtained with other calix-crowns,11 the
incorporation of a crown-4 at the narrow rim results in the cone
conformation of the dibromo-compound 2 and, consequently, the
yellow diacridinium compound 3 (see Scheme 1). Reaction of the
acridinium ion with methanol in the presence of a base easily
affords the corresponding colorless acridane compound 4.
In order to maintain two hydroxyl groups at the narrow rim the
cone-calix[4]arenes 7 and 8 were synthesized using the protected
derivative 5 (Scheme 2).
* Corresponding author. Tel.: þ49 30 2093 7348; fax: þ49 30 2093 7266.
E-mail address: abraham@chemie.hu-berlin.de (W. Abraham).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.082

L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
5937
CH3
N+
CH3
N+
i
BuLi, -78 °C
N
-
2 PF6
Br
Br
Br
Br
ii
i
BuLi
TsO
O
O
O OTs
ii
iii NH4PF6
O
O
O
O
O
O
O
O
O
O
O
O
O
O
H
H
O
O
2
3
1
CH3
CH3
N
MeOH/K2CO3
- 2 HPF6
N
OMe
MeO
O
O
O
O
O
O
4
Scheme 1. Synthesis of compounds 3 and 4.
Compound 11 was synthesized as a model for the acridinium
unit present in 7 (Scheme 3).
equatorial protons of the methylene bridges resonate with a differ-
ence of 0.9 ppm.7
Compound 8 resembles the narrow rim fourfold substituted
derivatives 2–4 (see Fig. 2).
2.2. Conformation
Also, in the case of 8, the difference of the resonances of the
equatorial and axial protons of the methylene bridges is 1 ppm in
CDCl3 solution. We were not able to crystallize the acridinium-
substituted derivative 7. However, according to the difference of
The calixarenes 2–4 exhibit a pinched-cone conformation in the
solid state (see Fig. 1). Compounds 3 and 4 are also assumed to
adopt a pinched-cone conformation in solution since the axial and
CH3
N+
CH3
N+
i
BuLi, -78 °C
N
-
2 PF6
Br
Br
Br
Br
ii
i
BuLi
O
MEM-Cl
ii
iii NH4PF6
O
O
O
O
O
O
O
O
O
O
O
O
H
H
O
O
O
O
O
O
O
O
5
6
1
HPF6
CH3
N+
CH3
N+
CH3
CH3
N
N
-
2 PF6
MeOH/K2CO3
- 2 HPF6
OMe
MeO
O
O
O
O
H
O
O
H
O
O
H
H
8
7
Scheme 2. Synthesis of compound 8.

5938
L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
N+
N+
Br
i 2 BuLi/THF
-
-
PF6
PF6
ii N-methylacridone
iii NH4PF6
HPF6
O
O
OH
O
O
O
O
9
10
11
Scheme 3. Synthesis of compound 11.
0.82 ppm in the resonances of the methylene protons, we can as-
sign a distorted cone conformation.
The crystal structure of 3 reveals that the torsion angle between
the acridinium unit and the aryl group of the calixarene is 75ꢀ.
Because one part of the acridinium unit points toward the cavity of
the calixarenes, the proton resonances are upfield shifted com-
pared with the resonance of protons, which are outside (see
Scheme 4). Obviously, a rotation of the acridinium unit against the
calixarene skeleton does not occur on the NMR time scale. A closer
look at the monosubstituted calix[4]arene 1211 at higher resolution
(600 MHz NMR) reveals that this derivative also exhibits a double
set of proton signals (Scheme 4). Indeed, the split is much larger if
two acridinium groups are present on the calixarene skeleton.
As acridinium compounds, the acridane calixarenes 4 and 8
exhibit a large 99ꢀ torsion angle between the acridane moiety and
the aryl group of the calixarene skeleton (see Figs. 1 and 2). In these
cases, however, only one set of proton resonances corresponding to
the acridane units appears in the NMR spectra. Accordingly, a rapid
rotation around the bond connecting the two groups in solution
can be assumed.
Figure 2. Structure of 8 with acetone as guest.
CH3
N+
CH3
N+
CH3
N+
O
O
O
O
O
O
-
O
-
PF6
2 PF6
O
O
O
3
12
Scheme 4.
2.3. Deprotonation of compounds 7 and 11
N+
N+
N
p-Hydroxyphenylacridinium ions such as 7 and 11 are both an
acid and a pseudo acid (see Scheme 5).
HO-
LiOH
-
+ PF6
OH
-
A quinonoid system such as 11q would be formed by dissocia-
tion of the ion pair giving rise to a bathochromic shift of the longest
wavelength absorption band of the parent acridinium system (see
Fig. 3). In fact, the addition of LiOH is accompanied by a dramatic
shift in the visible absorption (lmax¼680 nm (11) and 720 nm (7),
see Figs. 3 and 4). The reaction was performed by successive ad-
ditions of aliquots of 0.01 M LiOH in water to 2.5 mL of an aceto-
nitrile solution of 7 or 11. Therefore, in acetonitrile solution a rather
strong coordination of the cation to the phenolate unit is expected
(11s in Scheme 5).
Surprisingly, a second absorption band around 500 nm was
observed with other bases such as Et4NOH, NaOH, KOH, and CsOH
(see Fig. 5).
Qualitatively, the model compound 11 and the calixarene 7
show similar behavior. Only the ratio of the two long-wavelength
absorption bands is different. Obviously, the observed color
PF6
OLi
OH
OH
11
11s
- Li+
N
O
11q
Scheme 5. Acid–base behavior of compound 11.
Figure 1. Crystal structures of calixarenes 2–4.

L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
5939
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
acridane
11s
11
200
300
400
500
600
wavelength in nm
700
800
900
200
300
400
500
wavelength / nm
600
700
800
900
Figure 3. Absorption spectra of compound 11 (6.6ꢂ10ꢁ5 M in MeCN solution) re-
Figure 5. UV–vis spectra of compounds 7 d (MeCN, 4.8ꢂ10ꢁ5 M) and 11 - - (MeCN,
corded after addition of LiOH (0, 3.2ꢂ10ꢁ4, 5.6ꢂ10ꢁ4, 6.4ꢂ10ꢁ4, 8ꢂ10ꢁ4, 1.2ꢂ10ꢁ3
1.3ꢂ10ꢁ3 M).
,
9.1ꢂ10ꢁ5 M) before and after addition of KOH (10
m
L, 0.1 M¼4ꢂ10ꢁ4 M final
concentration).
changes are not a property of the calixarene scaffold with acridi-
nium substituents, but, rather, are inherent to the p-hydroxy-
phenylacridinium moiety. By participation of the acridinium unit at
the calixarene framework, the reaction with a nucleophile is much
slower. The blue color of 11 is not stable due to the reaction of the
primary formed deprotonated acridinium salt with nucleophiles
such as OHꢁ or EtOH present in the solution, which forms the
colorless acridane compound (see Scheme 5), but a stable blue
compound was formed from calixarene 7 and LiOH (Fig. 4). We
were able to record the NMR spectrum of the blue compound and
found that it does not match the expected spectrum of a quinonoid
compound. Both the resonances of the N-methyl group and of the
aryl protons of the acridinium moiety are only slightly upfield
shifted as compared to the original acridinium compound (see
Scheme 6).
narrow rim of the calixarene. Consequently, 6Li NMR spectros-
copy of the blue solution formed by addition of LiOH reveals
that the Li-resonance is low-field shifted (1.6 ppm) in compar-
ison to LiBr (0 ppm). The acetonitrile solution of Li-phenolate
exhibits a Li-resonance at 2.2 ppm. Accordingly, the blue color is
attributed to the increased electron donor (Li-phenolate)/ac-
ceptor (acridinium moiety) interaction. The phenolate acridi-
nium units of the calixarene are more planar than in the parent
acridinium ions. In fact, unlike the parent acridinium calixarene
the deprotonated salt exhibits only a single set of proton reso-
nances for the acridinium protons (compare Fig. 2, Supple-
mentary data).
The absorption spectrum of the deprotonated species is strongly
influenced by the cation of the base. With tetraethylammonium
hydroxide a shorter wavelength absorption band at 490 nm is
formed instead of the longer wavelength absorption band de-
scribed above (see Fig. 6).
The presence of Liþ is necessary to form the species with the
uniform UV–vis absorption band at 715 nm. The base di-iso-
propylethylamine is too weak to deprotonate the OH-groups,
and no changes of the absorption spectrum of 7 can be ob-
served. However, the addition of neutral LiBr leads to the for-
mation of the blue salt (see Fig. 1, Supplementary data). Thus, Li
ions must be strongly coordinated at the oxygen atoms at the
The addition of other hydroxide bases results in the formation of
two species represented by the two absorption bands at 490 and
720 nm. The ratio of the two species depends on the cation used.
The larger the cation, the stronger is the absorption band at
490 nm. Therefore, the nature of the cation can be identified with
the naked eye by the solution color (see Fig. 7).
Using CsOH, a red solid could be separated, which was soluble in
chloroform and insoluble in acetonitrile. By atomic absorption
spectroscopy, no Cs ions could be detected. Therefore, we assume
that this species and accordingly the absorption band at 490 nm are
attributed to the quinonoid structure of 7 (Scheme 7).
Unfortunately the NMR spectrum of the solid in CDCl3 solution
exhibits only very broad signals, which could not be used to assign
specific proton resonances of the quinonoid structure. But the po-
sition of the signals does not contradict the quinonoid structure
(compare Fig. 3, Supplementary data). The NMR spectrum of the
solution recorded after 6 days matches that of the corresponding
acridane (Supplementary data). We were not able to crystallize the
red compound.
1.0
0.5
0.0
The nucleophile OHꢁ attacks the deprotonated species and
forms the colorless acridane, which is assignable by the absorp-
tion band at 285 nm. This reaction seems to start from the salt-
like deprotonated species, because the absorption band at 715 nm
is more rapidly lost than that at 490 nm (see Fig. 4, Supplemen-
tary data). However, in the case of the Li-salt, this reaction is very
slow.
300
400
500
wavelength in nm
600
700
800
900
Figure 4. Absorption spectra of compound 7 (2.4ꢂ10ꢁ5 M in MeCN solution) recorded
after successive addition of LiOH (4ꢂ10ꢁ6, 1.6ꢂ10ꢁ5, 2.4ꢂ10ꢁ5, 3.2ꢂ10ꢁ5, 4ꢂ10ꢁ5
4.8ꢂ10ꢁ5, 5.6ꢂ10ꢁ5, 6.4ꢂ10ꢁ5 M).
,

5940
L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
4.80
8.58
8.35
7.80
N+
N+
N+
N+
8.60
8.40
7.90
7.89
6.79
6.96
6.96
8.30
7.12
7.51
7.51
TFA
H 3.24
H 4.49
H 3.67
H 4.50
HO
O
O
OH
O
O
O
O
Li
Li
4.11
4.00
1.9
2.14
1.42
1.15
Scheme 6. Changes of proton resonances on going from the salt formed by addition of LiOH to the parent acridinium compound 7 by addition of trifluoroacetic acid (TFA).
4
N
N
3
2
1
0
1
0
O
O
O
O
Scheme 7. Deprotonated structure proposed for the species with the visible absorp-
tion at 490 nm.
changes in substituents at the wide or narrow rim can result in
dramatic changes in binding properties.12 Surprisingly, sodium
cations are bound by the acridinium calixarene 3 and not by the
corresponding acridane. The association constant of 3/Naþ
300
400
500
wavelength / nm
600
700
800
(9.46ꢂ103ꢃ1.41ꢂ103 Mꢁ2
,
D
H¼ꢁ7.57ꢃ1.34ꢂ10 kcal Mꢁ1
;
D
S¼ꢁ7.2
cal Kꢁ1 molꢁ1) is considerably smaller than that of 2/Naþ. Unlike the
1:1 stoichiometry of 2/Naþ two host molecules 3 bind one sodium
ion. In all cases the complex formation is enthalpy driven.
The lack of binding of Naþ by 4 is most interesting because, in
principle, the non-binding state (acridane calixarene) can be
transformed into the binding state (acridinium calixarene) by
photoheterolysis (see below).
Figure 6. UV–vis spectra of 7 (0) (3.8ꢂ10ꢁ5 M) and absorption spectrum recorded
after addition of Et4NOH (1) (4ꢂ10ꢁ4 M).
2.4. Complexation studies
The small crown moiety at the narrow rim of compounds 2–4
should bind small inorganic cations such as Liþ and Naþ. Complex-
ation studies using isothermal titration calorimetry (ITC) (Fig. 5,
Supplementary data) revealed that compound 2 forms complexes
Calixarenes in their cone conformation are able to bind organic
cations in the p
-basic cavity in nonpolar solvents.5,7 Also the host 8
with Liþ (K¼1.23ꢂ105ꢃ1.49ꢂ104 Mꢁ1
,
D
H¼ꢁ5.16ꢃ0.09 kcal molꢁ1
;
,
bearing two acridane units at the upper rim forms complexes with
guests 13–16 in CDCl3 solution with relatively small complexation
constants (Scheme 8). In contrast, the corresponding acridinium-
substituted calixarene does not bind these guests.
The crystal structure of 8 (Fig. 2) reveals a pinched-cone con-
formation with a cavity large enough to include guests such as 13–
16. Complexation constants were determined with the help of NMR
titration (see Scheme 8). Because the strongest complexation in-
duced shifts of the proton signals, the methyl groups of the guest,
along with the ammonium or the iminium part of the organic
cations, appear to point into the cavity.
D
D
S¼5.9 cal Kꢁ1 molꢁ1
)
and
Naþ
(K¼6.73ꢂ105ꢃ1ꢂ105 Mꢁ1
H¼ꢁ10.41ꢃ1.25 kcal molꢁ1
;
D
S¼ꢁ8.3 cal Kꢁ1 molꢁ1) in acetoni-
trile solution. In contrast, the acridane and acridinium-substituted
calixarenes 3 and 4 do not bind lithium ions. It is known that small
2.5. Photoreaction
Acridanes such as 4 and 8 represent photochromic compounds
because upon photoexcitation in solutions containing alcohols,
acridinium methoxides formation occurs.13 The formed alkoxide
ion attacks the formed acridinium ion to restore the acridane. One
percent methanol is sufficient to obtain a reversible reaction. The
lifetime of the acridinium ion depends on the concentration and
the nature of the alcohols and ranges between seconds and hours.
Two species with lifetimes of 82 s and 785 s (ratio 2:1, Supple-
mentary data) were observed in acetonitrile solution of 4 con-
taining 1% methanol. A solution of 4 or 8 in acetonitrile/ethanol 4:1
Figure 7. Compound 7 in acetonitrile solution (4ꢂ10ꢁ5 M) and addition of several
bases (6.6ꢂ10-5 M); from left to right: 1: without base, 2: LiOH, 3: NaOH, 4: KOH, 5:
RbOH, 6: CsOH, 7: Et4NOH.

L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
5941
CH3
necessary (see above). In the presence of any alcohol, the back re-
action giving the acridane is much faster than the formation of the
quinonoid compound. Accordingly also in these cases a uniform
photoreaction is observed (see Fig. 9).
CH3
N
N
OMe
MeO
Because acridinium-substituted calixarenes are formed due to
the photolysis, complexes of the acridane hosts with guests would
be destroyed.
O
O
O
O
O
H
H
3.0
2.5
2.0
1.5
1.0
0.5
0.0
8
O
NMe3
13
K = 38 13 M-1
Ph
N+
14
K = 1461 458 M-1
N+
N+
15
16
K = 117 16 M-1
K = 35 3 M-1
Scheme 8. Guests used for complexation with host 8.
was irradiated with a mercury lamp equipped with filter glass
(l>300 nm) for several seconds. The conversion was followed by
250
300
350
wavelength / nm
400
450
500
UV–vis spectroscopy. The presence of isosbestic points indicated
that the photochemical process is a unimolecular conversion (see
Fig. 8). Both acridane moieties of 4 are involved. With high light
intensities (HBO 500, OSRAM), more than 70% turnover is observed
upon 40 s irradiation time. In general, the quantum yield of the
acridane photolysis is in the range of 0.5.13
Figure 9. UV–vis absorption spectra recorded after consecutive irradiation (313 nm: 0,
0,5, 1, 2, 4, 10, 20 min) of the calixarene
8 in acetonitrile/EtOH solution (4:1,
3.0ꢂ10ꢁ5 M).
3. Conclusions
2.5
Tetra- and dialkylated calix[4]arenes exhibiting the cone con-
formation and bearing acridinium and acridane substituents at the
wide rim were studied regarding their response to photoexcitation.
All compounds with acridane groups at the wider rim underwent
photoheterolysis to give the corresponding acridinium methoxides,
which reacted back to the acridane moieties in a thermal reaction.
The acridane calixarenes represent photochromic systems. Only the
acridinium-substituted calix crown-4 binds sodium ions. Therefore,
due to photolysis of acridane substituted calix crown-4, Naþ ions
are picked up from the solution. Only the calixarene having p-
hydroxyphenylacridane subunits within the calixarene framework
are able to bind organic cations in chloroform solution with mod-
erate complexation constants.
The deprotonation of the p-hydroxyphenylacridinium subunits
of the calixarene results in two different species with UV–vis ab-
sorption bands at 490 and 715 nm, respectively. The ratio of these
two species depends strongly on the cation of the base. Alkali
cations can be identified with the naked eye by the color of the
solution.
CH3
N
CH3
N
CH3
N+
CH3
N+
2.0
1.5
1.0
0.5
0.0
2 MeO-
O
OMe
O
MeO
hν
O
O
O
O
O
H
O
H
H
H
300
400
wavelength / nm
500
600
Figure 8. UV–vis spectra recorded after consecutive irradiation of a solution of com-
pound4(acetonitrile/ethanol4:1, 5.4ꢂ10ꢁ5 M)with lightof313 nmwavelength(3.10 s).
The kinetic trace recorded at 360 nm follows a biexponential
decay (Supplementary data) with two species of the lifetime 256 s
and 2250 s. The switching cycle can be repeated at least 10 times
without any fading of the starting compound. Because the starting
calixarene does not bind sodium ions, due to the photoreaction
these ions were picked up from the solution and released during
the thermal back reaction.
The photolysis of compound 8 generates, besides the acridinium
compounds, a methoxide ion, which could deprotonate the OH-
groups to give the quinonoid neutral compounds. But, for a suc-
cessful switching cycle the presence of at least 1% alcohol is
4. Experimental part
4.1. General
Commercially available chemicals and solvents (UVASOL,
Merck) were used as received unless otherwise noted; solvents
were dried according to standard procedures. Column chroma-
tographies (CC) were carried out on 200 mesh silica gel (Merck).
Melting points (mp) were determined with a Boetius heating mi-
croscope. ESI mass spectroscopy was carried out on LTQ FT, Fin-
nigan MAT (Bremen, Germany) equipped with an electrospray ion

5942
L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
source (Thermo Electron). NMR spectra were recorded on a Bruker
DPX 300 (300 MHz), a Bruker Advance 400 (400 MHz), and
a Bruker AMX 600 (600 MHz) instruments. The proton signals were
attributed to the different subunits with the aid of two-di-
mensional NMR spectroscopy, such as C–H-COSY, H–H-COSY, and
ROESY. UV–vis measurements were performed with a Shimadzu
UV 2101 PC spectrometer. Irradiation of the calixarene solutions
was carried out with a conventional mercury arc (HBO 500 or HBO
200) combined with a cut-off filter of 300 nm or metal in-
terference filters. The thermal reactions were followed by UV-vis
spectroscopy using the kinetics-program of the spectrometer. The
absorption decay curves at the wavelength of 360 nm were ana-
lyzed by nonlinear regression fits (Origin 6.0, Microcal Software,
Inc.). Transient absorption spectra between 340 and 500 nm were
recorded with the UV 2101 PC spectrometer using the fastest scan
mode.
4.3. Synthesis
Compound 12 was available from previous studies.11
4.3.1. 11,23-Di-bromo-25,27-dihydroxy-26,28-bis-
(propyloxy)calix[4]arene-crown-4 cone (2)
Compound 116 (3.33 g, 5 mmol) was suspended in dry THF
(100 mL). Buthyllithium (6.5 mL 1.6 M solution in hexane,
10.5 mmol) in dry THF (3.5 mL) was added dropwise. The solution
was diluted with acetonitrile (200 mL). Triethylene glycol bisto-
sylate (2.5 g, 5 mmol) in acetonitrile (200 mL) was added drop-
wise within 2 h. The solution was boiled at reflux for 6 h. The
solvent was removed in vacuo. The remaining residue was dis-
solved in dichloromethane. The solution was washed with water,
HCl (10%) and water. The solution was dried (MgSO4) and evap-
orated in vacuo. The residue was recrystallized (acetonitrile) to
provide a colorless solid (3.5 g, 90%), mp 225–228 ꢀC. Anal. Calcd
for C40H44Br2O6 (780.60): C, 61.55; H, 5.68; Br, 20.47. Found: C,
61.62; H, 5.62; Br, 20.37; HRMS (ESI, pos., MeOH): [MþNaþ]þ calcd
for C40H44 Br2O6Na: 801.1402, found: 801.1427. 1H NMR (400 MHz,
4.2. Determination of stability constants
4.2.1. Binding constants
CDCl3, TMS):
d
¼calixarene: 7.27 (s, 4H, H-10, 12, 22, 24), 6.27 (t,
Binding studies were carried out by means of 1H NMR titrations
of guest solutions at usually at a concentration of 1 mmol. In-
creasing amounts of the host were added up to host/guest of 50:1 to
200:1 ratio (20–80% saturation). The temperature was 298 K. Up-
field shifts of the resonances of different protons of the guest were
monitored in order to calculate binding constants K and the upfield
J¼7.4 Hz, 2H, H-5, 17), 6.15 (d, J¼7.4 Hz, 4H, H-4, 6, 16, 18), 4.35 (d,
2J¼15.7 Hz, 4H, H-2, 8, 14, 20), 3.12 (d, 2J¼15.7 Hz, 4H, H-2, 8, 14,
20), 3.64 (t, 4H, –OCH2CH2CH3), 1.92 (q, 4H, –OCH2CH2CH3), 1.12 (t,
6H, –OCH2CH2CH3); crown: 4.09 (s, 8H), 3.76 (s, 4H). 13C NMR
(100 MHz, CD3CN, TMS):
d
¼157.4 (C-25, 27), 154.7(C-26, 28), 138.8
(C-1, 9, 13, 21), 132.2 (C-3, 7,15, 19), 131.6 (C-10, 12, 22, 24), 127.7
(C-4, 6, 16, 18), 122.4 (C-5, 17), 114.7 (C-11, 23), 77.3
(–OCH2CH2CH3), 30.3 (C-2, 8, 14, 20), 23.6 (–OCH2CH2CH3), 10.9
(–OCH2CH2CH3); crown: 74.0 (CH2, 2C), 71.9 (CH2, 2C), 70.2 (CH2,
4C).
shift of the guests fully saturated by the host dGC
.
Titration data points
d
¼f(R) were fitted to the equation14
ꢀ
ꢁ
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
d
¼
dG ꢁ ðDd=2Þ b ꢁ b2 ꢁ 4R
with b¼1þRþ1/(K[H0]) and R¼[H]/[G] H¼host, G¼guest,
4.3.2. 11,23-Di-(N-methylacridinium-9-yl)-25,27-hydroxy-26,28-
bis(propyloxy)calix[4]arene-crown-4 bis hexafluorophosphate
cone (3)
Dd
¼
dGꢁ
dGC
Best fit parameters K and dGC were obtained in a nonlinear least-
square fitting procedure using the curve fitting program ‘Sigma
Plot’ (Jandel Scientific Software).
A solution of 2 (1.17 g, 1.5 mmol) in dry THF (100 mL) was cooled
to ꢁ78 ꢀC under argon. Butyllithium (2 mL 1.6 M solution in hex-
ane, 3.2 mmol) dissolved in THF (8 mL) was added dropwise. The
reaction mixture was stirred at ꢁ78 ꢀC for 0.5 h. N-Methylacridone
(0.63 g, 3.01 mmol) was added. The reaction mixture was slowly
warmed to room temperature under argon. Water (1 mL) was
added. The solvents were removed in vacuo. The remaining residue
was dissolved in acetonitrile and treated with NH4PF6 (2.5 g). The
solution was evaporated in vacuo. The remaining solid was washed
with water and methyl-tert-butylether (MTBE). The crude product
was purified by CC (acetonitrile/ethylacetate/cyclohexane/NH4PF6
400 mL/200 mL/100 mL/1 g); yellow crystals, 0.22 g (11%),
mp>325 ꢀC. Anal. C68H66F12N2O6P2 (1297.23); HRMS (ESI, pos.,
MeCN): [MꢁPF6ꢁ]þ calcd for C68H66N2O6PF6: 1151.4563, found:
1151.4549; [Mꢁ2PF6ꢁ]2þ calcd for C68H66N2O6: 503.2460, found:
Maximum errors for the K values were estimated as ꢃ15%.
4.2.2. Microcalorimetric measurements
An isothermal calorimetry instrument VP-ITC (MicroCal) was
used. The Differential Power axis (DP in
m
cal sꢁ1) of the ITC in-
strument was calibrated electrically using an internal electric
heater. Enthalpy and equilibrium constant were determined from
the titration curve using the Origin plotting software. At least three
independent measurements were carried out at 298 K. Each titra-
tion experiment consisted of 70 successive injections performed. A
constant volume (1 mL/injection) of the metal salt acetonitrile so-
lution was injected into the cell (1.4255 mL) charged with the cal-
ixarene solution (acetonitrile, 2ꢂ10ꢁ4 M). The heat of dilution
caused by the addition of the metal salt solution to the blank so-
lution without the calixarene was determined in each run. The
dilution enthalpies were subtracted from the enthalpies measured
during the titration experiment.
503.2463. 1H NMR (400 MHz, CD3CN, TMS):
d¼acridinium: 8.68 (d,
4H, H-5, 4), 8.41 (t, 2H, H-6), 8.37 (t, 2H, H-3), 8.08 (d, 2H, H-8), 7.90
(d, 2H, H-7), 7.77 (t, 2H, H-2), 7.73 (d, 2H, H-1), 4.84 (s, 6H, –Nþ–
CH3); calixarene: 7.63 (s, 4H, H-10, 12, 22, 24), 7.19 (d, 4H, 3J¼7.5 Hz,
H-4, 6, 16, 18), 6.94 (t, 2H, 3J¼7.5 Hz, H-5, 17), 4.67 (d, 4H,
2J¼13.0 Hz, H-2, 8, 14, 20), 4.52 (t 4H, 3J¼5.8 Hz, –OCH2CH2CH3),
3.75 (d, 4H, 2J¼13.0 Hz, H-2, 8, 14, 20), 2.00 (m, 4H, –OCH2CH2CH3),
0.95 (t, 6H, 3J¼7.3 Hz, –OCH2CH2CH3); crown: 4.30 (m, 8H, CH2),
4.2.3. X-ray crystallographic studies
Compounds 2–4 and 8 were obtained in monocrystalline form
by slow cooling of the warm acetonitrile and acetone solution, re-
spectively. Data were collected with a STOE-diffractometer using
4.14 (s, 4H, CH2). 13C NMR (75 MHz, CD3CN, TMS):
d
¼acridinium:
graphite-monochromated Mo K
a
radiation (details are given in
160.3 (C-9),142.0 (C-10a),141.9 (C-4a),139.0 (C-6),138.7 (C-3),130.5
(C-8), 129.9 (C-1), 128.2 (C-7), 128.1 (C-2), 126.3 (C-8a), 125.7 (C-9a),
119.0 (C-5), 118.8 (C-4), 39.2 (Nþ–CH3); calixarene: 154.7(C-26, 28),
151.8 (C-25, 27),136.9 (C-1, 9,13, 21),136.2 (C-3, 7,15,19),132.1 (C-10,
12, 22, 24),131.2 (C-11, 23), 130.0 (C-4, 6, 16, 18), 126.6 (C-5, 17), 79.8
(–OCH2CH2CH3), 30.1 (C-2, 8, 14, 20), 22.3 (–OCH2CH2CH3), 9.0
(–OCH2CH2CH3); crown: 75.1 (2C, CH2), 70.1 (4C, CH2).
Supplementary data). The structures were solved by direct
methods (SHELXS-97) and refined by full-matrix least-squares
techniques against F2 (SHELXL-97).15 The hydrogen atoms were
included at calculated positions. All other nonhydrogen atoms were
refined anisotropically. The X-STEP-Program was used for structure
representations.

L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
5943
4.3.3. 11,23-Di-(9-methoxy-9,10-dihydro-N-methylacridine-9-yl)-
25,27-dihydroxy-26,28-bis-(propyloxy)calix[4]arene-crown-4
cone (4)
The remaining residue was dissolved in acetonitrile (mL) and
treated with NH4PF6 (2.5 g). The solution was evaporated in
vacuo. The remaining solid was washed with water and MTBE.
The crude product was purified by CC (acetonitrile/ethylacetate/
cyclohexane/NH4PF6 400 mL/200 mL/100 mL/1 g); yellow crys-
tals, 0.96 g (36%), mp 208–210 ꢀC. Anal. C70H72N2O8P2F12
(1359.25); HRMS (ESI, pos., MeCN): [MꢁPFꢁ6 ]þ calcd for
C70H72N2O8PF6: 1213.4931, found: 1213.4913; [Mꢁ2PFꢁ6 ]2þ calcd
for C70H72N2O8: 534.2644, found: 534.2645. 1H NMR (400 MHz,
A suspension of 3 (0.11 g, 0.1 mmol) in acetonitrile (9 mL) and
methanol (1 mL) and K2CO3 (0.10 g) was stirred at room temper-
ature for 5 h. After filtration the solvents were removed in vacuo.
The residue was treated with dry chloroform (10 mL) and then
filtered. The filtrate was evaporated in vacuo. After recrystallization
(acetone) a colorless solid was obtained, 0.85 g, (79%), mp¼192–
195 ꢀC. Anal. C70H72N2O8 (1069.36); HRMS (ESI, pos., MeOH):
[MþNaþ]þ calcd for C70H72N2O8Na: 1091.5186, found: 1091.5198;
[MꢁOCHꢁ3 ]þ calcd for C69H69N2O7: 1037.5105, found: 1039.5122;
[Mꢁ2OCHꢁ3 ]2þ calcd for C68H66N2O6: 503.2460, found: 503.2468.
CD3CN, TMS):
d
¼acridinium: 8.51 (d, J¼9.0 Hz, 2H, H-5), 8.41
(ddd, 3J¼9 Hz, 3J¼8 Hz, 4J¼1 Hz, 2H, H-6) 8.20 (dd, 3J¼8.8 Hz,
4J¼1 Hz, 2H, H-8), 7.91 (ddd, 3J¼9 Hz, 3J¼8 Hz, 4J¼1 Hz, 2H, H-7),
7.83 (d, J¼9.0 Hz, 2H, H-4), 7.00 (dt, 3J¼9 Hz, 4J¼1 Hz, 2H, H-3),
6.22 (t, J¼8 Hz, 2H, H-2), 5.89 (dd, 3J¼8 Hz, 4J¼1 Hz, 2H, H-1) 4.56
(s, 6H, –Nþ–CH3); calixarene: 7.17 (d, J¼7.3 Hz, 4H, H-4, 5, 16, 18),
6.77 (t, J¼8 Hz, 2H, H-5, 17), 6.74 (s, 4H, H-10, 12, 22, 24), 5.31 (s,
4H, –OCH2O–), 4.67 (d, 4H, 2J¼13.3 Hz, H-2, 8, 14, 20), 4.20 (m,
4H, –OCH2CH2CH3), 4.06 (m, 4H, –OCH2OCH2CH2OCH3), 3.62 (m,
4H, –OCH2OCH2CH2OCH3), 3.55 (d, 4H, 2J¼13.3 Hz, H-2, 8, 14, 20),
3.35 (6H, –OCH2OCH2CH2OCH3), 2.25 (m, 4H, –OCH2CH2CH3), 1.06
(t, 6H, –OCH2CH2CH3). 13C NMR (100 MHz, CDCl3, TMS)
1H NMR (400 MHz, CD3CN, TMS):
d¼acridane: 7.35 (t, 4H, J¼7.8 Hz,
H-1, 8), 7.28 (d, 4H, J¼7.8 Hz, H-2, 7), 7.16 (d, 4H, J¼7.8 Hz, H-4, 5),
6.95 (t, 4H, J¼7.8 Hz, H-3, 6) 3.51 (s, 6H, –N–CH3) 3.01 (s, 6H,
–OCH3); calixarene: 7.09 (s, 4H, H-10, 12, 20, 24), 6.74 (d, 4H,
J¼7.5 Hz, H-4, 6, 16, 18), 6.61 (t, 2H, J¼7.5 Hz, H-5, 17), 4.21 (d, 4H,
H-2, 8, 14, 20), 3.33 (d, 4H, H-2, 8, 14, 20); crown: 4.01 (m, 8H,), 3.91
(s, 4H); ether: 4.01 (m, 4H, –OCH2CH2CH3), 1.75 (m, 4H,
–OCH2CH2CH3), 0.82 (t, 6H, 3J¼7.5 Hz, –OCH2CH2CH3). 13C NMR
(100 MHz, CD3CN, TMS):
d¼acridane: 141.2 (C-4a, 5a), 129.1 (C-1,
d
¼acridinium: 140.9, 139.7, 138.6 (C-6), 136.2, 135.5 (C-3), 134.9,
8), 128.3 (C-3, 6), 124.3 (C-1a, 8a), 120.4 (C-2, 7), 113.1 (C-4, 5), 78.7
(C-9), 51.1 (–OCH3), 33.4 (–NCH3); calixarene: 152.3 (C-25, 27), 151.7
(C-26, 28) 147.2 (C-11, 23), 135.7 (C-1, 9, 13, 21), 134.5 132.5 (C-3, 7,
15, 19), 128.9 130.0 (C-4, 6, 16, 18), 126.6 128.2 (C-10, 12, 20, 24),
125.7 121.4 (C-5, 17), 73.8 (–OCH2CH2CH3), 29.9 (C-2, 8, 14, 20), 22.1
(–OCH2CH2CH3), 9.0 (–OCH2CH2CH3); crown: 79.0 (2C, CH2), 70.0
(4C, CH2).
130.6 (C-8), 129.2 (C-1), 127.7 (C-7), 125.4 (C-2), 124.6, 123.3, 117.9
(C-5), 116.7 (C-4), 38.2 (–Nþ–CH3); calixarene: 132.1 (C-10, 12, 22,
24), 128.9 (C-4, 5, 16, 18), 123.0 (C-5, 17), 99.8 (–OCH2O–), 76.7
(–OCH2CH2CH3), 71.4 (–OCH2CH2OCH3), 69.4 (–OCH2CH2OCH3),
57.8 (–OCH2CH2OCH3), 30.6 (C-2, 8, 14, 20), 22.9 (–OCH2CH2CH3),
9.2 (–OCH2CH2CH3).
4.3.6. 11,23-Di-(N-methylacridinium-9-yl)-25,27-hydroxy-26,28-
4.3.4. 11,23-Di-bromo-25,27-bis(2-methoxy-ethoxymethoxy)-
26,28-bis(propyloxy)calix[4]arene (5)
bis(propyloxy)calix[4]arene bis hexafluorophosphate (7)
Compound
6 (0.30 g, 0.22 mmol) dissolved in acetonitrile
Butyllithium (6.5 mL 1.6 M in hexane, 10.4 mmol) was added to
a solution of 1 (3.33 g, 5 mmol) in THF (125 mL). After stirring for
0.5 h methoxyethoxymethyl chloride (MEM chloride, 1.25 g,
10 mmol) in THF (20 mL) was added. The solution was stirred at
room temperature for 3 h. The solvent was removed in vacuo. The
residue was dissolved in chloroform (100 mL) and washed with
water (4ꢂ50 mL). After drying (MgSO4) the solution was evapo-
rated. The remaining solid was purified by recrystallization (n-
hexane), 3.8 g (90%), mp 102–104 ꢀC. Anal. Calcd for C42H50Br2O8
(842.66): C, 59.87; H, 5.98; Br, 18.96. Found: C, 60.12; H, 6.05; Br,
(25 mL) was treated with HPF6 (0.2 mL) and water (0.4 mL) under
stirring for 1 h. After evaporating the solution, the remaining solid
was washed with water (5 mL) and MTBE (10 mL). The remaining
solid was purified by CC (acetonitrile/ethylacetate/cyclohexane/
NH4PF6 400 mL/200 mL/100 mL/1 g), 0.195 g (75%), orange solid,
mp¼325 ꢀC. Anal. C62H56 F12N2O4P2 (1183.03); HRMS (ESI, pos.,
MeCN): [MꢁPF6ꢁ]þ calcd for C62H56N2O4PF6: 1037.3882, found:
1037.3869; [Mꢁ2PF6ꢁ]2þ calcd for C62H56N2O4: 446.2120, found:
446.2117. 1H NMR (600 MHz, (CD3)2CO, TMS):
d
¼acridinium: 8.80
(d, 2H, 3J¼7.2 Hz, H-5), 8.77 (d, 2H, J¼7.2 Hz, H-4), 8.42 (t, 2H,
3J¼7.2 Hz, H-6), 8.39 (t, 2H, 3J¼7.2 Hz, H-3), 8.31 (d, 2H, 3J¼8.4 Hz,
H-8), 8.11 (d, 2H, 3J¼8.4 Hz, H-1), 7.93 (t, 2H, 3J¼8.4 Hz, H-7), 7.84 (t,
2H, 3J¼8.4 Hz, H-2), 5.00 (s, 6H, –Nþ–CH3); calixarene: 9.38 (s, 2H,
OH), 7.53 (s, 4H, H-10, 12, 22, 24), 7.08 (d, 4H, 3J¼7.5 Hz, H-4, 6, 16,
18), 6.80 (t, 2H, 3J¼7.5 Hz, H-5, 17), 4.48 (d, 4H, 2J¼13.0 Hz, H-2, 8,
14, 20), 4.08 (t 4H, 3J¼5.8 Hz, –OCH2CH2CH3), 3.67 (d, 4H,
2J¼13.0 Hz, H-2, 8, 14, 20), 2.13 (m, 4H, –OCH2CH2CH3), 1.40 (t, 6H,
3J¼7.3 Hz, –OCH2CH2CH3). 13C NMR (75 MHz, CD3CN, TMS):
19.02; 1H NMR (400 MHz, CDCl3, TMS):
d¼7.18 (s, 4H, H-10, 12, 22,
24), 6.33 (t, 3J¼7.5 Hz, 2H, H-5, 17), 6.19 (d, 3J¼7.5 Hz, 4H, H-4, 5, 16,
18), 5.23 (s, 4H, –OCH2O–), 4.36 (d, 4H, 2J¼13.6 Hz, H-2, 8, 14, 20),
3.95 (m, 4H, –OCH2OCH2CH2OCH3), 3.64 (t, 4H, 3J¼7.3 Hz,
–OCH2CH2CH3), 3.54 (m, 4H, –OCH2OCH2CH2OCH3), 3.36 (s, 6H,
–OCH2OCH2CH2OCH3), 3.11 (d, 4H, 2J¼13.6 Hz, H-2, 8, 14, 20), 1.79
(m, 4H, –OCH2CH2CH3), 1.00 (t, 6H, 3J¼7.5 Hz, –OCH2CH2CH3). 13C
NMR (100 MHz, CDCl3, TMS):
138.8 (C-1, 9, 13, 21), 132.4 (C-3, 7, 15, 19), 131.4 (C-10, 12, 22, 24),
d
¼155.1 (C-25, 27), 154.7 (C-26, 27),
d
¼acridinium 161.9,155.0,151.9,141.4,138.3 (C-6),138.1 (C-3),133.5,
127.9 (C-4, 5, 16, 18), 122.6 (C-5, 17), 115.4 (C-11, 23), 98.9 (–OCH2O),
130.5 (C-8), 130.0 (C-1), 128.4, 127.3 (C-7, 2), 125.8 (C-8a, 9a), 118.2
(C-5), 118.1 (C-4); calixarene 131.0 (C-10,12, 22, 24),129.1 (C-4, 6,16,
18), 125.9 (C-5, 17), 123.8 (C-11, 23), 78.5 (–OCH2CH2CH3), 38.3
(–Nþ–CH3), 30.3 (C-2, 8, 14, 20), 23.1 (–OCH2CH2CH3), 10.1
(–OCH2CH2CH3).
76.7
(–OCH2CH2CH3),
72.2
(–OCH2OCH2CH2OCH3),
69.7
(–OCH2OCH2CH2OCH3), 59.1 (–OCH2OCH2CH2OCH3), 31.0 (C-2, 8,
14, 20), 23.3 (–OCH2CH2CH3), 10.6 (–OCH2CH2CH3).
4.3.5. 11,23-Di-(N-methylacridinium-9-yl)-25,27-bis(2-methoxy-
ethoxymethoxy)-26,28-bis(propyloxy)calix[4]arene bis
4.3.7. 11,23-Di-(9-methoxy-N-methylacridine-9-yl)-25,27-
hexafluorophosphate (6)
hydroxy-26,28-bis(propyloxy)calix[4]arene (8)
A solution of 5 (2.11 g, 2.5 mmol) in dry THF (150 mL) was
cooled to ꢁ78 ꢀC under argon. Butyllithium (3.13 mL 1.6 M solu-
tion in hexane, 5.01 mmol) dissolved in THF (8 mL) was added
dropwise. The reaction mixture was stirred at ꢁ78 ꢀC for 0.5 h. N-
Methylacridone (1.05 g, 5.02 mmol) was added. The reaction
mixture was slowly warmed to room temperature under argon.
Water (1 mL) was added. The solvents were removed in vacuo.
The suspension of 7 (0.050 g, 0.48 mmol) and KHCO3 (0.05 g) in
acetonitrile (4 mL) and methanol (1 mL) was stirred for 5 days. The
product precipitated and was filtrated together with KHCO3. The
solid was washed with water until the water was neutral. The solid
was dried and recrystallized from acetonitrile, 0.037 g (75%),
mp¼148 ꢀC (dec). Anal. C64H62N2O6 (955.22); HRMS (ESI, pos.,
MeOH): [Mꢁ2MeOꢁ]2þ calcd for C62H56N2O6: 446.2120, found:

5944
L. Grubert et al. / Tetrahedron 65 (2009) 5936–5944
446.2127. 1H NMR (400 MHz, CDCl3, TMS):
d¼acridane: 7.28 (t,
F6NOP (431.32); HRMS (ESI, pos., MeCN): [MꢁPFꢁ6 ]þ calcd for
3J¼8.3 Hz, 4H, H-3, 6), 7.21 (dd, 3J¼7.8 Hz, 4J¼1.5 Hz, 4H, H-1, 8),
7.03 (d, 3J¼8.3 Hz, 4H, H-4, 5), 6.70 (dt, 3J¼7.8 Hz, 4J¼1.5 Hz, 4H, H-
2, 7), 3.54 (s, 6H, Nþ–CH3); calixarene: 8.28 (s, 2H, –OH), 7.00 (s, 4H,
H-10, 12, 22, 24), 6.73 (d, 3J¼8.0 Hz, 4H, H-4, 6, 16, 18), 6.66 (t,
3J¼8.0 Hz, 2H, H-5, 17), 4.21 (d, 2J¼13,1 Hz, 4H, H-2, 8, 14, 20), 3.88
(t, 3J¼6.3 Hz, 4H, –OCH2CH2CH3), 3.25 (d, 2J¼13,1 Hz, 4H, H-2, 8, 14,
20), 2.90 (s, 6H, –OCH3), 1.98 (m, 4H, –OCH2CH2CH3), 1.26 (t, 6H,
3J¼7.6 Hz, –OCH2CH2CH3). 13C NMR (100 MHz, CDCl3, TMS):
C20H16NO: 286.1232, found: 286.1240. 1H NMR (400 MHz, CD3CN,
TMS):
d
¼9.20 (s, 1H, –OH), 8.55 (d, 2H, 3J¼9.3 Hz, H-4, 5) 8.34 (t, 2H,
3J¼9.3 Hz, H-3, 6), 8.13 (d, 2H, 3J¼8.8 Hz, H-1, 8), 7.83 (t, 2H,
3J¼8.8 Hz, H-2, 7), 7.37 (d, 2H, 3J¼8.7 Hz, –C6H4OH), 7.16 (d, 2H,
3J¼8.7 Hz, –C6H4OH), 4.78 (s, 3H, Nþ–CH3). 13C NMR (100 MHz,
(CD3CN, TMS):
d¼162.0, 158.6, 141.3, 138.2 (C-3, 6), 131.8 (o-
C6H4OH), 130.2 (C-1, 8), 127.2 (C-2, 7), 126.0, 124.0, 118.0 (C-4, 5),
115.4, (m-C6H4OH), 38.3 (–Nþ–CH3).
d
¼acridane: 141.2 (C4a, 5a), 130.0(C-1, 8), 128.2 (C-3, 6), 125.0 (C-1a,
8a), 120.0 (C-2, 7), 112.0 (C-4, 5), 78.9 (C-9), 51.1 (–OCH3), 33.5
(–NCH3); calixarene: 152.0 (C-26, 28), 151.8 (C-25, 27), 138.0 (C-1, 9,
13, 21), 133.4 (C-3, 7, 15, 19), 129.9 (C-11, 23), 128.9 (C-4, 6, 16, 18),
127.4 (C-10,12, 22, 24),125.4 (C-5,17), 78.1 (–OCH2CH2CH3), 31.7 (C-
2, 8, 14, 20), 23.5 (–OCH2CH2CH3), 11.0 (–OCH2CH2CH3).
Acknowledgements
Financial
support
provided
by
Deutsche
For-
schungsgemeinschaft is gratefully acknowledged.
Supplementary data
4.3.8. 9-[4-(2-Methoxy-ethoxymethoxy)-phenyl]-N-
methylacridinium hexafluorophosphate (10)
UV–vis, NMR spectra as well as crystallographic data are avail-
able in Supplementary data. Transient decay curves are given in
supplement information. Supplementary data in the form of a CIF
have been deposited with the Cambridge Crystallographic Data
Centre (CCDC 730189 for 2, CCDC 730186 for 3, CCDC 730188 for 4,
and CCDC 730187 for 8). Supplementary data associated with this
article can be found in the online version, at doi:10.1016/
j.tet.2009.05.082.
A solution of 1-Bromo-(2-methoxy-ethoxymethoxy)-phenyl]-
benzene (9)17 (2.61 g, 10 mmol) in dry THF (100 mL) was cooled to
ꢁ78 ꢀC under argon. Butyllithium (3.15 mL 1.6 M solution in hexane,
5.04 mmol) dissolved in THF (6 mL) was added dropwise. The re-
action mixture was stirred at ꢁ78 ꢀC for 0.5 h. N-Methylacridone
(2.1 g, 10.1 mmol) was added. The reaction mixture was slowly
warmed to room temperature under argon. Water (1 mL) was added.
The solvents were removed in vacuo. The remaining residue was
dissolved in acetonitrile (50 mL) and treated with NH4PF6 (2.5 g). The
solution was evaporated in vacuo. The remaining solid was washed
with water and MTBE. The crude product was purified by CC (aceto-
nitrile/ethylacetate/cyclohexane/NH4PF6 400 mL/200 mL/100 mL/
1 g); yellow crystals, 2.27 g (44%), mp 128–130 ꢀC. Anal. C24H24
F6NO3P (519.43); HRMS (ESI, pos., MeCN): [MꢁPFꢁ6 ]þ calcd for C24H24
NO3: 374.1756, found: 374.1754. 1H NMR (400 MHz, CD3CN, TMS):
References and notes
1. Gutsche, C. D. Calixarenes; Royal Society of Chemistry: Cambridge, England,
1989; Calixarenes: A Versatile Class of Macrocyclic Compounds; Vicens, J., Bo¨hmer,
V., Eds.; Kluwer: Dordrecht, 1991; Pochini, A.; Ungaro, R. In Comprehensive
Supramolecular Chemistry; Vo¨gtle, F., Ed.; Pergamon: Oxford, 1996; Vol. 2,
pp 103–142; Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 1713–1734.
2. Wang, L.; Vysotsky, M. O.; Bogdan, A.; Bolte, M.; Bo¨hmer, V. Science 2004, 304,
1312.
3. Ikeda, A.; Shinkai, S. J. Am. Chem. Soc. 1994, 116, 3102.
4. Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; Wiley-VCH: Chichester,
2000.
5. Abraham, W. J. Inclusion Phenom. Macrocycl. Chem. 2002, 43, 159.
6. Gutsche, C. D.; Alam, I. Tetrahedron 1988, 4689.
7. Orda-Zgadzaj, M.; Wendel, V.; Fehlinger, M.; Ziemer, B.; Abraham, W. Eur. J. Org.
Chem. 2001, 1549.
8. Deng, G.; Sakaki, T.; Kawahara, Y.; Shinkai, S. Tetrahedron Lett. 1992, 33, 2163.
9. Husaru, M.; Gruner, T.; Wolff, W. D.; Habicher; Salzer, R. Tetrahedron Lett. 2005,
46, 3377.
10. Scha¨fer, C.; Eckel, R.; Ros, R.; Mattay, J.; Anselmetti, D. J. Am. Chem. Soc. 2007,
129, 1488.
d
¼8.57 (d, 2H, 3J¼9.3 Hz, H-4, 5) 8.36 (t, 2H, 3J¼9.3 Hz, H-3, 6), 8.09 (d,
2H, 3J¼8.8 Hz, H-1, 8), 7.84 (t, 2H, 3J¼8.8 Hz, H-2, 7), 7.46 (d, 2H,
3J¼8.7 Hz,–C6H4OMEM), 7.37(d, 2H, 3J¼8.7 Hz,–C6H4OMEM), 5.42(s,
2H, –OCH2O–), 4.80 (s, 3H, –Nþ–CH3), 3.85 (m, 2H, –OCH2CH2OCH3),
3.56 (m, 2H, –OCH2CH2OCH3), 3.30 (s, 3H, –OCH2CH2CH3). 13C NMR
(100 MHz, (CD3CN, TMS):
d
¼161.5, 158.6, 141.3, 138.3 C-3, 6), 131.5
(o-C6H4OMEM),130.0(C-1, 8),127.4(C-2,7),126.0,125.9,118.1(C-4,5),
116.2, (m-C6H4OMEM), 93.07 (–OCH2O–), 71.04 (–OCH2CH2OCH3),
67.8 (–OCH2CH2OCH3), 57.6 (–OCH2CH2CH3), 38.4 (–Nþ–CH3).
4.3.9. 9-(4-Hydroxy-phenyl)-N-methylacridinium
hexafluorophosphate (11)
11. Grubert, L.; Abraham, W. Tetrahedron 2007, 63, 10778.
12. Casnati, A.; Pochini, A.; Ungaro, R.; Bocchi, C.; Ugozzoli, F.; Egberink, R. J. M.;
Strujk, H.; Lugtenberg, R.; de Jong, F.; Reinhoudt, D. N. Chem.dEur. J.1996, 2, 436.
13. Abraham, W.; Buck, K.; Orda-Zgadzaj, M.; Schmidt-Scha¨ffer, S.; Grummt, U.-W.
Chem. Commun. 2007, 3094.
A solution of HPF6 (1 mL) in water (4 mL) was added to a stirred
solution of 10 (1.0 g) in acetonitrile (50 mL). The solution was
evaporated in vacuo. The remaining solid was washed with water
(10 mL) and MTBE (20 mL). The remaining solid was purified by
CC acetonitrile/ethylacetate/cyclohexane/NH4PF6 400 mL/200 mL/
100 mL/1 g); 0.73 g (87%), yellow solid, mp186–188 ꢀC. Anal. C20H16
14. Macomber, R. S. J. Chem. Educ. 1992, 69, 375–378.
15. Sheldrick, G. M. SHELXL-97; Universita¨t Go¨ttingen: Go¨ttingen, Germany, 1997.
16. Casnati, A.;Pochini, A.;Ungaro, R.; Ugozzoli, F.;Arnaud, F.;Fanni, S.; Schwing, M.-J.;
Egberink, R. J. M.; de Jong, F.; Reinhoudt, D. N. J. Am. Chem. Soc. 1995, 117, 2767.
17. Chuang, C.-L.; dos Santos, O.; Xu, X.; Canary, J. W. Inorg. Chem. 1997, 36, 1967.