Systematic approach to new ligands for anion recognition based on ureido-calix[4]arenes

Article abstract of DOI:10.1039/b802871k

Mono, di-, tri- and tetraureido-calix[4]arenes in the cone, partial cone and 1,3-alternate conformations have been synthesised and their complexation ability towards selected anions has been studied. The structure-anion complexation ability relationship has been systematically monitored. A new type of very efficient ligands based on diureido-calix[4]arene in a 1,3-alternate conformation with pronounced bonding ability towards carboxylates was designed. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Full text of DOI:10.1039/b802871k

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PAPER
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Systematic approach to new ligands for anion recognition based
on ureido-calix[4]arenesw
a
a
a
b
´
Ivan Stibor,* Jan Budka, Veronika Michlova, Marcela Tkadlecova,
Michaela Pojarova, Petra Curınova and Pavel Lhotak*
´
c
a
a
ˇ
´
´
´
´
Received (in Durham. UK) 19th February 2008, Accepted 21st April 2008
First published as an Advance Article on the web 10th June 2008
DOI: 10.1039/b802871k
Mono, di-, tri- and tetraureido-calix[4]arenes in the cone, partial cone and 1,3-alternate
conformations have been synthesised and their complexation ability towards selected anions has
been studied. The structure–anion complexation ability relationship has been systematically
monitored. A new type of very efficient ligands based on diureido-calix[4]arene in a 1,3-alternate
conformation with pronounced bonding ability towards carboxylates was designed.
calix[4]arenes systematically. Here we report, on the synthesis,
Introduction
binding ability and selectivity profile of several ureido-
calix[4]arenes with one to four urea units appended to the
calix[4]arene skeleton in cone, partial-cone and 1,3-alternate
conformations.
The complexation of anionic species continues to attract the
attention of the chemical community as witnessed by numer-
ous reviews published recently.1 The importance of anions in
biological systems is well recognised. The same is true for the
role of anions in chemical processes and environmental pollu-
tion. Given their importance, there has obviously been much
effort expended in the design of anion complexing ligands. The
main strategies have traditionally focused on cationic, poly-
ammonium, quanidinium, quaternary ammonium, porphyrin-
based ligands, and a number of Lewis-acid containing ligands.
Neutral organic ligands for anion binding via favourable
hydrogen bonding have also been thoroughly studied and
recently reviewed.2 Calixarenes are extremely versatile macro-
cyclic compounds with well developed chemistry and abun-
dant literature.3 Many neutral organic ligands based on the
calixarene macrocyclic skeleton have been reported in litera-
ture. For this work the most relevant are calixarene-based
neutral ligands having no metal ion inherently bound. A
number of such ligands have been used for binding of anions4
or cation–anion couples.5 Our own research has been oriented
to anion recognition using simple (hetero)aromatic amides,6a–c
ureas6d or calixarene-based ligands.6e–h Working with the
calixarene based ligands for anions we have found that bis-
(phenyluredio)-calix[4]arene in cone conformation is able to
bind benzoate with surprisingly high selectivity. Moreover,
tetrakis(phenylureido)-calix[4]arene in 1,3-alternate confor-
mation has been found to bind anions with negative allosteric
effect.6e We have also examined calixarene based cages6f as
well as calixarene–porphyrin based ligands.6g The unexpected
results6e mentioned above have prompted us to study ureido-
Results and discussion
Design
Thirteen ureido-calix[4]arenes have been chosen for the study of
structure–anion binding ability relationship (Fig. 1). Compounds
1, 10 and 14 have been already mentioned.6e Monoureido
derivative 2 is used in comparison with 1 and 4 to study the
cooperation of two and three ureido groups. Accordingly,
comparison of 1, and 3 would tell us more about the role of
proximity in cooperative action of two ureido groups. The role of
the substituent on the other side of the urea unit (apart from the
calixarene moiety) can be easily evaluated by comparison of
1 (phenyl), 5 (benzyl), 6 (cyclohexyl) and 8 (1-(1-naphthylethyl)).
The role of lower rim substitution can be illustrated by compar-
ison of ligands 1 (tetraalkoxy) and 7 (distal-dihydroxydialkoxy).
All the above mentioned compounds have been built on the
calix[4]arene skeleton in cone conformation. The role of the
calixarene conformation can be assessed by comparison of
1 (cone), 9 (partial cone), 10 (1,3-alternate-tetrasubstituted) and
13 (1,3-alternate-disubstituted) for phenylureido compounds or 5
(cone) and 11 (1,3-alternate-tetrasubstituted), 8 (cone), 12 (1,3-
alternate-tetrasubstituted). The unique role of 1,3-alternate
calix[4]arene skeleton flexibility can be easily estimated by
comparison of tetrasubstituted 10 and disubstituted 13.
Synthesis
a Department of Organic Chemistry, Institute of Chemical Technology,
Technicka 5, 166 28 Prague 6, Czech Republic.
E-mail: Ivan.Stibor@vscht.cz; Pavel.Lhotak@vscht.cz;
Fax: +420-220444280; Tel: +420-220444288
The synthesis of compounds 1, 10 and 14 has been mentioned pre-
viously.6e In general, the synthesis of ligands described is straight-
forward following the traditional sequence: calix[4]arene—
nitration to nitrocalix[4]arene—reduction to aminocalix[4]-
arene—reaction with aryl isocyanate to form ureido-calix[4]arene.
All known intermediates we have used in our synthetic procedures
are cited in the Experimental section. Nitration of calix[n]arenes is
a well described procedure. Nevertheless, we have had to develop
b Department of Analytical Chemistry, Institute of Chemical
Technology, Technicka 5, 166 28 Prague 6, Czech Republic
c Department of Solid State Chemistry, Institute of Chemical
Technology, Technicka 5, Prague 6, 166 28, Czech Republic
w CCDC reference number 678255. For crystallographic data in CIF
or other electronic format see DOI: 10.1039/b802871k
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Fig. 1 Prepared urea derivatives of calix[4]arene.
a method for the synthesis of 5,17-dinitro-25,26,27,28-tetrapro-
poxycalix[4]arene in both 1,3-alternate (15) and partial cone (16)
conformations (Scheme 1). In this context we have used the
alkylation of 5,17-dinitro-25,27-dipropoxycalix[4]arene-26,28-diol7
with propyl iodide templated by caesium carbonate in DMF. This
procedure led to a mixture of 15 and 16 in 26 and 67% yields,
Scheme 1 Preparation of new nitro and amino derivatives.
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respectively. Separation of these conformers can be achieved only
by column chromatography which makes the procedure some-
what laborious for pure 15 despite the great difference in chro-
complexation constants in both solvent systems requires several
comments. A negative allosteric effect already observed6e in
solvent A is retained also in solvent B. The diameter of the
halide anions is reflected by complexation ability only for the
conformationaly rigid ligand 10. The extraordinary preference
of ligand 1 for benzoate is not retained in solvent B that can be
explained by the loss of the cooperative action of both hydrogen
bonding and p–p stacking interaction due to better solvation of
aromatic moieties of both ligand and anion by DMSO.15 This is
reflected by the ratio of complexation constants of benzoate/
acetate by ligand 1 that has changed from almost 41 in solvent A
to less than 4 in solvent B. This phenomenon deserves further
attention and is under study in our laboratory.
16
matographic mobility of both compounds (RF15 = 0.4 and RF
= 0.9). There are several methods for preparation of amino-
substituted calix[4]arenes described in literature. In our hands
the reduction by SnCl2 dihydrate7b,8,9 was found to give
the best results in terms of yield and purity of sometimes
unstable amino-calix[4]arenes. Thus, we have prepared all pre-
viously described amino-calix[4]arenes, namely 5-amino-25,26,
27,28-tetrapropoxycalix[4]arene (cone),9 5,11-diamino-25,26,27,
28-tetrapropoxycalix[4]arene (cone),9,10 5,17-diamino-25,26,27,28-
tetrapropoxycalix[4]arene (cone),9,10 5,17-diamino-25,27-dipro-
poxycalix[4]arene-26,28-diol (cone),11 5,11,17,23-tetraamino-25,26,
27,28-tetrapropoxycalix[4]arene (cone),12 5,11,17,23-tetraamino-
25,26,27,28-tetrapropoxycalix[4]arene (1,3-alternate),9 as well as
new amino-calix[4]arenes, namely 5,11,17-triamino-25,26,27,28-
tetrapropoxycalix[4]arene (cone) (17), 5,17-diamino-25,26,27,28-
tetrapropoxycalix[4]arene (1,3-alternate) (18), 5,17-diamino-25,26,
27,28-tetrapropoxycalix[4]arene (partial cone) (19), in excellent
yields (Scheme 1). The synthesis of ureas was performed
using a standard reaction protocol13 with commercially available
isocyanates.
The cooperative action of ureido moieties on the same side
of calix[4]arene skeleton in the cone conformation can be
illustrated by examining the complexation ability of ligands
2, 1 and 4 having one, two and three ureas on the same side of
calixarene skeleton. Disubstituted ligand 3 was prepared to
illustrate the role of the substitution pattern of the upper rim
of the calix[4]arene skeleton in the binding process (proximal 3
vs. distal 1). The data obtained are summarised in Table 1.
Well known dimerisation phenomena have been described
for the upper-rim tetraurea derivatives of calix[4]arenes.16
These compounds form capsules due to their multiple hydro-
gen bonds in non-competitive solvents such as chloroform or
dichloromethane. All ureido derivatives, with the exception of
3 and 4, exhibit clear and concentration-independent 1H NMR
spectra. Triureido derivative 4 shows a strong concentration
dependence in solvent A (see Fig. 2). Unfortunately, all signals
are very broad and the self-aggregation cannot be determined
quantitatively. Fig. 3 shows the changes in spectra of com-
pound 4 after addition of 10% (v/v) of (CD3)2SO. The broad
and irresolvable signals changed into a clear spectrum. The
same situation has also been found in the case of proximal
diureido derivative 3 (Fig. 4). It seems that the self-aggregation
process is typical for calixarenes bearing ureido groups on
neighbouring aromatic units (proximal arrangement). Conse-
quently, the 1H NMR titrations of 3 and 4 were performed in
solvent B, where self-aggregation is not present at all.
Complexation
The complexation ability of the prepared compounds have been
screened by standard 1H NMR titration experiment using a
constant calixarene concentration (0.5–2.0 mM) and increasing
concentration of appropriate anion to obtain different host : guest
ratios (0.1–20 : 1).6e In order to compare all data obtained we
have used two solvents, namely A: CDCl3–CD3CN = 4 : 1 and
B: CDCl3–CD3SOCD3 = 4 : 1, both v/v. Compounds 1 and 10
have been taken as references and their complexation ability have
been measured in both solvent systems. The results obtained are
summarised in Tables 1–3.
In all but one case only formation of 1 : 1 complexes were
observed (Job plots)14 what means that in both solvents two
ureas positioned on one side of ligands 1 and 10 cooperate in
binding of one anion regardless its size, shape and solvation. The
only exception is compound 9 where cooperative action of both
ureido groups is not possible as witnessed by its X-ray structure
(see later). The data for ligands 1 and 10 in solvent A
have already been discussed.6e Anyhow, the comparison of
The following conclusions can be drawn from Tables 1 and 2.
The cooperation of both urea moieties in 1 (distal) is clearly
indicated by comparison with model compound 2 having only
one urea unit. Synchronous binding by both ureas is responsible
for enhancement of complex stability by more than two orders
Table 1 Complexation constants of cone ligands 1–4 and 7 towards selected anions (solvent A: CDCl3–CD3CN = 4 : 1 and B:
CDCl3–CD3SOCD3 = 4 : 1, v/v, 25 1C, 300 MHz)
KC/Mꢁ1
1
2
A
3
B
4
B
7
B
Anion
A6e
B
Clꢁ
390 ꢂ 20
110 ꢂ 20
40 ꢂ 7
4700 ꢂ 490
1400 ꢂ 160
710 ꢂ 190
2300 ꢂ 480
4000 ꢂ 1100
160 000 ꢂ 45 000
b
60 ꢂ 6
n.c.a
660 ꢂ 50
520 ꢂ 80
2100 ꢂ 190
160 ꢂ 70
80 ꢂ 10
240 ꢂ 90
180 ꢂ 30
n.c.a
60 ꢂ 10
20 ꢂ 10
n.c.a
420 ꢂ 20
250 ꢂ 20
130 ꢂ 10
Brꢁ
15 ꢂ 5
Iꢁ
H2PO4
MeCO2
PhCO2
n.c.a
ꢁ
ꢁ
ꢁ
b
900 ꢂ 130
3000 ꢂ 300
1500 ꢂ 300
350 ꢂ 120
1200 ꢂ 120
1300 ꢂ 120
—
880 ꢂ 190
1700 ꢂ 600
a
No complexation observed (CIS o 5 Hz). Not determined stoichiometry.
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Table 2 Complexation constants of ligands 1, 5, 6, 8 (cone) and 9 (partial cone) towards selected anions (solvent: CDCl3–CD3CN = 4 : 1, v/v, 25 1C,
300 MHz)
KC/Mꢁ1
Anion
16e
5
6
8
9
Clꢁ
4700 ꢂ 490
1400 ꢂ 160
710 ꢂ 190
410 ꢂ 50
1300 ꢂ 210
170 ꢂ 60
590 ꢂ 40
100 ꢂ 20
15 ꢂ 5
1100 ꢂ 160
290 ꢂ 60
130 ꢂ 50
Brꢁ
170 ꢂ 30
Iꢁ
H2PO4
MeCO2
PhCO2
130 ꢂ 40
60 ꢂ 20
ꢁ
ꢁ
ꢁ
a
2300 ꢂ 480
4000 ꢂ 1100
160 000 ꢂ 45 000
1100 ꢂ 200
5800 ꢂ 1500
6200 ꢂ 820
530 ꢂ 260
1400 ꢂ 190
1700 ꢂ 110
770 ꢂ 270
90 ꢂ 10
—
2000 ꢂ 280
1700 ꢂ 200
8400 ꢂ 3400
a
Undetermined stoichiometry.
Table 3 Complexation constants of 1,3-alternate ligands 10–13 towards selected anions (solvent A: CDCl3–CD3CN = 4 : 1 and B:
CDCl3–CD3SOCD3 = 4 : 1, v/v, 25 1C, 300 MHz)
KC/Mꢁ1
10
13
11
A
12
B
Anion
A6e
B
A
B
Clꢁ
Brꢁ
Iꢁ
800 ꢂ 220
790 ꢂ 390
1800 ꢂ 550
3200 ꢂ 1000
1400 ꢂ 310
2100 ꢂ 300
4700 ꢂ 190
1500 ꢂ 90
570 ꢂ 90
140 ꢂ 20
80 ꢂ 20
60 ꢂ 20
20 ꢂ 10
36 000 ꢂ 13 000
2400 ꢂ 570
840 ꢂ 570
690 ꢂ 170
580 ꢂ 270
a
a
42 ꢂ 10
n.c.
n.c.
4200 ꢂ 1000
920 ꢂ 320
ꢁ
ꢁ
ꢁ
H2PO4
2700 ꢂ 300
2200 ꢂ 200
1800 ꢂ 700
200 ꢂ 60
620 ꢂ 300
750 ꢂ 360
250 ꢂ 40
100 ꢂ 20
50 ꢂ 20
6900 ꢂ 960
41 000 000
41 000 000
MeCO2
PhCO2
3500 ꢂ 1800
a
No complexation observed (CIS o 5 Hz).
of magnitude for benzoate, and around one order of magnitude
for halides. The comparison of distal and proximal disubstituted
ligands 3 and 1 revealed that a proximal substitution pattern is
better for chloride, dihydrogen phosphate and acetate whereas
distal is by far better for benzoate and larger spherical halides.
Using 4-nitrophenylurea in the same positions, an unusual
behaviour has been observed for proximal ligands of type 3.
In this case the complexation event has been found to promote
dimerisation of ligands around the central anion to form the
complexes with 2 : 1 (calix : anion) stoichiometry.17 Ligand 4
with three ureas is even better for chloride and acetate but less
suitable for dihydrogen phosphate and benzoate. The profound
difference between acetate and benzoate can be explained in
terms of a much smaller steric demand of the former and
absence of additional stacking interaction proven for later. In
general, smaller and compact anions are better bound by two
ureas in proximal position in contrast with larger and aromatic
anions that are better bound with two distal ureas. The third
urea did not bring much efficiency (max. 50%) in binding of any
anion studied. Considering their rather demanding synthesis, the
trisubstituted calixarenes did not seem to be prospective candi-
dates for further ligand development.
ppm shift of signals of these protons during the titration
experiment), (ii) the loss of rigidity (and/or directionality) of
aromatic units in 5 due to the CH2 spacer leading to possible
steric hindrance in the urea surroundings. As a result, a
substantial decrease of complexation constant is observed in
CDCl3–CD3CN solution for all anions except for acetate (see
Table 2). A similar situation can be seen in compound 6 where
the cyclohexyl unit is connected to the urea nitrogen via an sp3
carbon (most probably via an equatorial bond) giving higher
mobility to the cyclohexyl moiety compared to phenyl. As a
result, all complexation constants are much lower than those
for receptor 1. Chiral ligand 8 can be seen as a combination of
both 5 and 6 as the urea substituent is of benzyl type being
attached by a tertiary carbon atom. These two factors result in
severe loss of binding ability towards all anions. On the other
hand, the absolute value of the complexation constant for
benzoate (8400 ꢂ 340 Mꢁ1) indicates that this type of receptor
can be used for aromatic carboxylate recognition.
Very similar reasoning can be applied to ligands with the
calix[4]arene skeleton in a 1,3-alternate conformation. Ligands
10, 11 and 12 illustrate the situation by their complexation
data as summarised in Table 3.
The role of substituent R in ligands 1, 5, 6 and 8 can be
assessed by inspecting the data collected in Table 2. Compar-
ison of receptors 1 (aromatic ring directly connected to urea)
and 5 (benzyl derivative having the phenyl ring ‘‘isolated’’ by
one CH2 group from the urea moiety) indicates the role of the
substitution. Generally, two factors are in play simulta-
neously: (i) the loss of interaction between ortho-aromatic
hydrogens and anion in 5 (well documented for 1 by 40.5
Analogous behaviour was found for compounds with the
calix[4]arene skeleton in 1,3-alternate conformation. Again, a
severe decrease of complexation is seen for almost all cases
going from aryl urea (10) to benzyl (11) or naphthylmethyl
(12), except for acetate that is better bound by 10 and
dihydrogen phosphate that is better bound by 12. Tetrasub-
stituted ligands in a 1,3-alternate conformation showed a
negative allosteric effect for all anions studied. Moreover, since
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Fig. 3 Partial 1H NMR spectra of compound 4 at 298 K: (a) in
CDCl3, (b) in CDCl3–(CD3)2SO = 10 : 1 v/v mixture.
Obviously, albeit both receptors are immobilised in the
cone conformation, the derivative 1 exhibits much stronger
Fig. 2 Partial 1H NMR spectra of derivative 4 (CDCl3, 298 K) at
various concentrations: (a) 1 ꢃ 10ꢁ3 M, (b) 6 ꢃ 10ꢁ4 M, (c) 3 ꢃ 10ꢁ4
.
complexation (KCl = 4.7 ꢃ 103 Mꢁ1, KBr = 1.4 ꢃ 103 Mꢁ1
)
)
than calixarene 2 (KCl = 3.9 ꢃ 102 Mꢁ1, KBr = 1.1 ꢃ 102 Mꢁ1
their skeletons appear to be so rigid, ligands of this type did not
seem to be good candidates for further structural tuning.
In order to learn more about the role of flexibility of the
calix[4]arene skeleton in a 1,3-alternate conformation we decided
to study analogous compounds having only one side of skeleton
substituted with ureido functions. As we have shown tetrasub-
stituted receptors in a 1,3-alternate conformation behave as
monotopic receptors and only one cavity is used for anion
complexation. Hence, two ureido moieties can be omitted without
influencing the binding efficiency. Furthermore, one can expect
slightly higher flexibility of this type of receptor if compared with
10. This should enable the binding site to adopt the most suitable
conformation in terms of the induced fit principle.
possessing only one urea unit. The difference of one order of
Compound 13 is the first member of completely new ligand
design with surprisingly enhanced ability for anion binding.
The only difference, compared with receptor 10, is that two
additional ureido functions on the other side of the 1,3-alter-
nate calix[4]arene skeleton were ‘‘deleted’’ from the molecule.
Despite the fact that the structure difference is remote with
respect to the ureido binding pocket, the change in binding
ability is immediately apparent (see Table 3).
The effect of the number of urea units on the anion com-
plexation can be demonstrated by comparison of the binding
ability of diureido receptor 1 with that of model compound 2.
Fig. 4 Partial 1H NMR spectra of derivative 3 at 298 K: (a) in
CDCl3, (b) CDCl3–(CD3)2SO = 10 : 1 v/v.
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The solid-state structure of compound 9 was obtained by
single-crystal X-ray crystallography. This calixarene formed a
complex with water and ethanol molecules (Fig. 5) which
crystallised in the orthorhombic system with three screw axes
21 perpendicular to each other. Consequently, the molecules
form a helix in the crystal packing held together by hydrogen
bonds between ureido groups of each calixarene (CQO and
both NH-groups). This fact is clearly visible in the direction of
the b axis (Fig. 6). Every two molecules overlap in this
direction but are shifted to each other in the b direction by
b/2 thus creating infinite channels (from top view). A water
molecule forms a bridge between the helices and is bound in
two ways to ureido units—to the carbonyl group of one
molecule and on the opposite site to one of NH groups of
other molecules. Ethanol (crystallisation solvent) is then con-
nected via hydrogen bonds to the water molecule.
Conclusions
Fig. 5 X-Ray structure of the partial cone derivative 9; hydrogen
atoms are omitted for better clarity.
In conclusion, we have studied a number of ureido-calixarene-
based neutral ligands with different number and spatial positions
of ureido groups towards complexation of anions. This systema-
tic study resulted in the structure of ligand 13 which is regarded
as a new, very efficient scaffold that will be used for modular
construction of anion receptors with the possibility to be
extended to the recognition of chiral anions. We are currently
working on this project.
magnitude indicates the importance of a hydrogen bonding
array for effective anion binding (cooperative effect).
Similar results were found for ligand 9 having two ureas
attached to the calix[4]arene skeleton in the partial cone con-
formation. In this case, the substitution pattern prevents effective
cooperative action of urea moieties. As a consequence, disub-
stituted partial cone compound 9 binds all anions studied in very
similar manner as monosubstituted ligand 2. On the other hand,
the complexation data obtained for H2PO4ꢁ indicated that both
urea moieties of calixarene 9 can also act separately leading to
2 : 1 (anion : ligand) complex stoichiometry.
Experimental
Melting points were determined on a Boetius block (Carl Zeiss
Jena, Germany) and are not corrected. The IR spectra were
measured on an FT-IR spectrometer Nicolet 740 in CHCl3 and/
or in KBr. 1H NMR spectra were recorded on a Varian Gemini
300 spectrometer, the temperature-dependant spectra were re-
corded on Bruker AMX3 400 and Bruker DRX 500 Avance
spectrometers using tetramethylsilane as an internal standard.
Dichloromethane used for the reaction was dried with CaH2,
and stored over molecular sieves. The purity of the substances
and the courses of reactions were monitored by TLC using TLC
aluminium sheets with Silica gel 60 F254 (Merck). Preparative
TLC chromatography was carried out on 20 ꢃ 20 cm glass
plates covered by Silica gel 60 GF254 (Merck).
5,17-Bis(N0-phenylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (cone) 1
To a stirred solution of 100 mg (0.16 mmol) of 5,17-diamino-
24,25,26,27-tetrapropoxycalix[4]arene in 6 ml of dry dichloro-
methane 0.87 ml (8.0 mmol) of phenyl isocyanate was added.
The mixture was stirred at room temperature for 12 h and
poured into methanol to give 86 mg (63%) of compound 1 as a
white precipitate, mp 266–268 1C (Found: C, 75.0; H, 6.9; N,
6.6. C54H60N4O6 requires: C 75.32; H 7.02; N 6.51%; M+
860.4). dH (300 MHz; CDCl3; Me4Si): 7.32 (4H, m, Ar-H), 7.25
(4H, d, J 7.7, Ar-H), 7.12 (4H, d, J 7.7, Ar-H), 7.04 (2H, t, J
6.8, Ar-H), 6.93 (2H, t, J 7.2, Ar-H), 6.00 (4H, s, Ar-H), 4.46
(4H, d, J 13.4, Ar–CH2–Ar ax), 4.01 (4H, t, J 8.3, 2 ꢃ OCH2),
3.67 (4H, t, J 6.6, 2 ꢃ OCH2), 3.16 (4H, d, J 14.3, Ar–CH2–Ar
Fig. 6 Crystal packing of the partial cone derivative 9 showing
hydrogen bonding interactions; hydrogen atoms are omitted for
better clarity.
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eq), 1.96–1.83 (8H, m, 4 ꢃ OCH2CH2), 1.11 (6H, t, J 7.5, 2 ꢃ
CH3), 0.87 (6H, t, J 7.5, 2 ꢃ CH3). [M + H]+ 861.8.
(petroleum ether–chloroform 2 : 1) and then by preparative
TLC chromatography (petroleum ether–ethyl acetate 10 : 1) to
yield 65 mg (56%) of compound 4 as a yellowish powder, mp
208–210 1C (Found: C, 73.4; H, 6.6; N, 8.4. C61H66N6O7
5-(N0-Phenylureido)-24,25,26,27-tetrapropoxycalix[4]arene
(cone) 2
requires
C 73.62; H 6.68; N 8.44%). dH (300 MHz;
CDCl3–(CD3)2SO 10 : 1; Me4Si): 7.80 (1H, s, NHCO), 7.70
(2H, s, NHCO), 7.61 (1H, s, NHCO), 7.46 (2H, s, NHCO),
6.99 (2H, d, J 8.3, Ar-H), 6.89 (4H, d, J 7.7, Ar-H), 6.83–6.74
(6H, m, Ar-H), 6.54–6.46 (3H, m, Ar-H), 6.49 (2H, s, Ar-H),
6.42 (2H, d, J 7.7, Ar-H), 6.25 (1H, t, J 7.7, Ar-H), 6.23 (2H, s,
Ar-H), 6.16 (2H, s, Ar-H), 4.02 (2H, d, J 12.7, Ar–CH2–Ar
ax), 3.99 (2H, d, J 12.6, Ar–CH2–Ar ax), 3.54–3.44 (4H, m, 2
ꢃ OCH2), 3.31 (4H, t, J 7.2, 2 ꢃ OCH2), 2.72 (2H, d, J 13.6,
Ar–CH2–Ar eq), 2.68 (2H, d, J 12.6, Ar–CH2–Ar eq),
1.60–1.45 (8H, m, 4 ꢃ OCH2CH2), 0.61 (6H, t, J 7.2, 2 ꢃ
CH3), 0.55 (6H, t, J 7.2, 2 ꢃ CH3).
To a stirred mixture of 100 mg (0.16 mmol) of 5-amino-
24,25,26,27-tetrapropoxycalix[4]arene (cone) in 3 ml of dry
dichloromethane 0.4 ml (3.2 mmol) of phenyl isocyanate was
added. The mixture was stirred at room temperature for 12 h,
poured into methanol, stirred for 30 min and evaporated to
dryness. The residue was separated on 30 g of silica gel
(petroleum ether–ethyl acetate 10 : 1) to yield 80 mg (67%)
of compound 2 as a white powder, mp 137–140 1C (Found: C,
77.4; H, 7.4; N, 3.7. C47H54N2O5 requires C 77.65; H 7.49; N
3.85%). dH (300 MHz; CDCl3; Me4Si): 7.30 (2H, d, J 7.7, Ar-
H), 7.20 (2H, d, J 7.2, Ar-H), 7.06 (1H, t, J 7.7, Ar-H),
6.96–6.90 (4H, m, Ar-H), 6.81 (2H, d, J 7.2, Ar-H),
6.33–6.23 (3H, m, Ar-H), 6.26 (2H, s, Ar-H), 6.11 (1H, br s,
NHCO), 5.72 (1H, br s, NHCO), 4.46 (2H, d, J 13.7,
Ar–CH2–Ar ax), 4.45 (2H, d, J 13.7, Ar–CH2–Ar ax), 3.96
(4H, dt, J 7.2, J 6.0, 2 ꢃ OCH2), 3.76 (2H, t, J 7.2, OCH2), 3.73
(2H, t, J 7.7, OCH2), 3.16 (2H, d, J 13.2, Ar–CH2–Ar eq), 3.14
(2H, d, J 13.2, CH2-Ar eq), 1.97–1.88 (8H, m, 4 ꢃ OCH2CH2),
1.07 (3H, t, J 7.7, CH3), 1.05 (3H, t, J 7.2, CH3), 0.93 (6H, t, J
7.2, 2 ꢃ CH3).
5,17-Bis(N0-benzylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (cone) 5
To a stirred mixture of 100 mg (0.16 mmol) of 5,17-diamino-
24,25,26,27-tetrapropoxycalix[4]arene (cone) in 4 ml of dry
dichloromethane 0.2 ml (1.6 mmol) benzyl isocyanate was
added. The mixture was stirred at room temperature for
60 h, poured into methanol, stirred for 24 h and evaporated
to dryness. The residue was separated on 30 g of silica gel
(petroleum ether–ethyl acetate 10 : 1) and then by preparative
TLC chromatography (petroleum ether–ethyl acetate 4 : 1) to
yield 62 mg (44%) of compound 5 as a yellowish powder, mp
151–154 1C (Found: C, 75.5; H, 7.2; N, 6.3. C56H64N4O6
requires C 75.65; H 7.26; N 6.30%). dH (300 MHz; CDCl3;
Me4Si): 7.32 (4H, m, Ar-H), 7.25 (4H, d, J 7.7, Ar-H), 7.12
(4H, d, J 7.7, Ar-H), 7.04 (2H, t, J 6.8, Ar-H), 6.93 (2H, t, J
7.2, Ar-H), 6.00 (4H, s, Ar-H), 4.46 (4H, d, J 13.4, Ar–CH2–Ar
ax), 4.32 (4H, d , J 5.8, NHCH2-Ar), 4.01 (4H, t, J 8.3, 2 ꢃ
OCH2), 3.67 (4H, t, J 6.6, 2 ꢃ OCH2), 3.16 (4H, d, J 14.3,
Ar–CH2–Ar eq), 1.96–1.83 (8H, m, 4 ꢃ OCH2CH2), 1.11 (6H,
t, J 7.5, 2 ꢃ CH3), 0.87 (6H, t, J 7.5, 2 ꢃ CH3).
5,11-Bis(N0-phenylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (cone) 3
To a stirred mixture of 100 mg (0.16 mmol) of 5,11-diamino-
24,25,26,27-tetrapropoxycalix[4]arene (cone) in 4 ml of dry
dichloromethane 0.9 ml (7.2 mmol) of phenyl isocyanate was
added. The mixture was stirred at room temperature for 12 h,
poured into methanol, stirred for 30 min and evaporated to
dryness. The residue was separated on 40 g of silica gel
(petroleum ether–chloroform 2 : 1) and then by preparative
TLC chromatography (petroleum ether–ethyl acetate 10 : 1) to
yield 72 mg (52%) of 3 as a white powder, mp 171–174 1C
(Found: C, 75.1; H, 7.0; N, 6.5. C54H60N4O6 requires C 75.32; H
7.02; N 6.51%). dH (300 MHz; CDCl3–(CD3)2SO 10 : 1; Me4Si):
7.87 (2H, s, NHCO), 7.53 (2H, s, NHCO), 7.21 (4H, d, J 8.2, Ar-
H), 7.04 (4H, t, J 7.7, Ar-H), 6.75 (2H, t, J 7.7, Ar-H), 6.64 (2H,
s, Ar-H), 6.46–6.37 (6H, m, Ar-H), 6.31 (2H, s, Ar-H), 4.26 (1H,
d, J 13.2, Ar–CH2–Ar ax), 4.21 (2H, d, J 12.6, Ar–CH2–Ar ax),
4.20 (1H, d, J 13.2, Ar–CH2–Ar ax), 3.65 (4H, t, J 7.7, 2 ꢃ
OCH2), 3.59 (4H, t, J 7.6, 2 ꢃ OCH2), 2.95 (1H, d, J 13.2,
Ar–CH2–Ar eq), 2.93 (2H, d, J 13.2, Ar–CH2–Ar eq), 2.86 (1H,
d, J 13.2, Ar–CH2–Ar eq), 1.76–1.67 (8H, m, 4 ꢃ OCH2CH2),
0.80 (12H, t, J 7.2, 4 ꢃ CH3).
5,17-Bis(N0-cyclohexylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (cone) 6
To a stirred mixture of 100 mg (0.16 mmol) of 5,17-diamino-
24,25,26,27-tetrapropoxycalix[4]arene (cone) in 4 ml of dry
dichloromethane 0.4 ml (3.2 mmol) of cyclohexyl isocyanate
was added. The mixture was stirred at room temperature for
60 h, poured into methanol, stirred for 30 min and evaporated to
dryness. The residue was poured in 10 ml of acetone and filtered
off to yield 72 mg (52%) of title compound 6 as a white
precipitate, mp 192–195 1C (Found: C, 74.1; H, 8.2; N, 6.1.
C54H72N4O6 requires C 74.28; H 8.31; N 6.24). dH (300 MHz;
CDCl3; Me4Si): d: 7.29 (2H, s, NHCO), 7.04 (4H, d, J 7.7, Ar-
H), 6.88 (2H, t, J 7.7, Ar-H), 5.86 (4H, s, Ar-H), 5.71 (2H, s,
NHCO), 4.41 (4H, d, J 13.2, Ar–CH2–Ar ax), 3.95 (4H, t, J 8.2,
2 ꢃ OCH2), 3.66 (4H, t, J 6.6, 2 ꢃ OCH2), 3.62–3.44 (2H, m,
H–Cy), 3.11 (4H, d, J 13.7, Ar–CH2–Ar eq), 1.92–1.81 (10H, m,
4 ꢃ OCH2CH2 and H–Cy), 1.70–1.66 (4H, m, H–Cy), 1.62–1.58
(2H, m, H–Cy), 1.36–1.25 (6H, m, H–Cy), 1.28–1.08 (6H, m,
H–Cy), 1.08 (6H, t, J 7.2, 2 ꢃ CH3), 0.86 (6H, t, J 7.2, 2 ꢃ CH3).
5,11,17-Tris(N0-phenylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (cone) 4
To a stirred mixture of 75 mg (0.11 mmol) of 5,11,17-triamino-
24,25,26,27-tetrapropoxycalix[4]arene (cone) in 4 ml of dry
dichloromethane 0.38 ml (3.5 mmol) of phenyl isocyanate was
added. The mixture was stirred at room temperature for 12 h,
poured into methanol, stirred for 12 h and evaporated to
dryness. The residue was separated on 40 g of silica gel
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5,17-Bis(N0-phenylureido)-25,27-dipropoxycalix[4]arene-26,28-
diol (cone) 7
7.7, Ar-H), 4.00 (2H, d, J 13.2, Ar–CH2–Ar), 3.81–3.73 (2H,
m, OCH2), 3.65 (2H, t,
J 7.2, OCH2), 3.60 (2H, s,
Ar–CH2–Ar), 3.49 (2H, t, J 7.2, OCH2), 3.28 (2H, s,
Ar–CH2–Ar), 3.00 (2H, d, J 13.2, Ar–CH2–Ar), 1.92–1.77
(6H, m, 3 ꢃ OCH2CH2), 1.52–1.45 (2H, m, OCH2CH2), 1.06
(6H, t, J 7.7, 2 ꢃ CH3), 0.99 (3H, t, J 7.7, CH3), 0.68 (3H, t, J
7.7, CH3) (one of the signals of OCH2 is overlapped by signal
of DMSO).
To a stirred mixture of 100 mg (0.19 mmol) of 5,17-diamino-
25,27-dipropoxycalix[4]arene-26,28-diol (cone) in 6 ml of dry
dichloromethane 1.0 ml (9.3 mmol) of phenyl isocyanate was
added to give a white precipitate. The mixture was stirred at
room temperature for 12 h, poured into methanol and filtered
off to yield 100 mg (70%) of compound 7 as a white powder,
mp 4350 1C (Found: C, 74.0; H, 6.1; N, 7.2. C48H48N4O6
requires C 74.21; H 6.23; N 7.21%). dH (300 MHz; (CD3)2SO,
Me4Si): 8.49 (2H, s, NHCO), 8.26 (2H, s, OH), 8.19 (2H, s,
NHCO), 7.42 (4H, d, J 7.7, Ar-H), 7.25 (4H, t, J 8.0, Ar-H),
7.19 (4H, s, Ar-H), 7.04 (4H, d, J 7.2, Ar-H), 6.93 (2H, t, J 7.2,
Ar-H), 6.81 (2H, t, J 7.5, Ar-H), 4.20 (4H, d, J 12.7,
Ar–CH2–Ar ax), 3.95 (4H, t, J 7.7, 2 ꢃ OCH2), 3.41 (4H, d,
J 13.2, Ar–CH2–Ar eq), 2.01 (4H, m, 2 ꢃ OCH2CH2), 1.31
(6H, t, J 7.5, CH3).
5,11,17,23-Tetrakis(N0-phenylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (1,3-alternate) 10
To stirred solution of 100 mg (0.15 mmol) of 5,11,17,23-
tetraamino-24,25,26,27-tetrapropoxycalix[4]arene (1,3-alter-
nate) in 6 ml of dry dichloromethane 0.83 ml (7.5 mmol) of
phenyl isocyanate was added. The mixture was stirred at room
temperature for 12 h and poured into methanol to give a clear
solution. The mixture was stirred for 15 min and then evapo-
rated to dryness. The residue was dissolved in small amount of
methanol and stored overnight in a freezer to yield 86 mg
(50%) of compound 10 as a yellowish powder, mp 4350 1C
(Found: C, 72.3; H, 6.3; N, 9.7. C68H72N8O8 requires C 72.32;
H 6.43; N 9.92%; M+ 1128,6). dH (300 MHz; CDCl3, Me4Si):
7.84 (4H, br s, NHCO), 7.73 (8H, d, J 8.2, Ar-H), 7.35 (8H, m,
Ar-H), 7.09 (4H, t, J 7.2, Ar-H), 6.99 (8H, s, Ar-H), 6.56 (4H,
br s, NHCO), 3.72 (8H, t, J 7.2, 4 ꢃ OCH2), 3.47 (8H, s,
Ar–CH2–Ar), 1.88 (8H, m, 4 ꢃ OCH2CH2), 1.04 (12H, t, J 7.2,
4 ꢃ CH3) [M + Na]+ 1151.6.
5,17-Bis[(R)-(ꢁ)-1-(1-naphthyl)ethylureido]-24,25,26,27-
tetrapropoxycalix[4]arene (cone) 8
To a stirred mixture of 100 mg (0.16 mmol) of 5,17-diamino-
24,25,26,27-tetrapropoxycalix[4]arene (cone) in 6 ml of dry
dichloromethane 0.17 ml (0.96 mmol) (R)-(ꢁ)-1-(1-naphthyl)-
ethyl isocyanate was added. The mixture was stirred at room
temperature for 12 h, poured into methanol to give a white
precipitate. The precipitate was filtered off to yield 96 mg
(63%) of title compound 8 as a yellowish powder, mp 260–262 1C
(Found: C, 77.8; H, 7.0; N, 5.5. C66H72N4O6 requires C 77.92;
H 7.13; N 5.51%). dH (300 MHz; CDCl3, Me4Si): 8.05 (2H, m,
Ar-H), 7.85 (2H, m, Ar-H), 7.76 (2H, m, Ar-H), 7.49–7.46
(4H, m, Ar-H), 7.39 (4H, s, Ar-H), 6.98 (2H, m, Ar-H), 6.92
(2H, m, Ar-H), 6.80 (2H, br s, NHCO), 6.56 (2H, br s,
NHCO), 5.89 (4H, d, J 6.6, Ar-H), 5.73-5.66 (4H, m, CH
and Ar-H), 4.38 (2H, d, J 13.2, Ar–CH2–Ar ax), 4.36 (2H, d, J
13.7, Ar–CH2–Ar ax), 3.93 (4H, t, J 7.7, 2 ꢃ OCH2), 3.61 (4H,
t, J 6.6, 2 ꢃ OCH2), 3.08 (2H, d, J 14.2, Ar–CH2–Ar eq), 3.02
(2H, d, J 14.8, Ar–CH2–Ar eq), 1.92–1.81 (8H, m, 4 ꢃ
OCH2CH2), 1.54 (6H, d, J 6.6, 4 ꢃ CH3), 1.06 (6H, t, J 7.7,
2 ꢃ CH3), 0.84 (6H, t, J 7.7, 2 ꢃ CH3).
5,11,17,23-Tetrakis(N0-benzylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (1,3-alternate) 11
To a stirred mixture of 100 mg (0.15 mmol) of 5,11,17,23-
diamino-24,25,26,27-tetrapropoxycalix[4]arene (1,3-alternate)
in 4 ml of dry dichloromethane 0.38 ml (3.0 mmol) benzyl
isocyanate was added. The mixture was stirred at room
temperature for 60 h, poured into methanol, stirred for 24 h
and evaporated to dryness. The residue was dissolved in
chloroform and precipitated by methanol to yield 42 mg
(23%) of 5,11,17,23-tetrakis(N0-benzylureido)-24,25,26,27-tetra-
propoxycalix[4]arene (1,3-alternate) 11 as a yellowish powder,
mp 208–212 1C (Found: C, 72.7; H, 6.8; N, 9.4. C72H80N8O8
requires C 72.95; H 6.80; N 9.45%). dH (300 MHz; CDCl3,
Me4Si): 7.34 (20H, br s, Ar-H), 6.89 (8H, s, Ar-H), 6.96–6.78
(4H, m, NHCO), 6.18–6.00 (4H, m, NHCO), 4.47 (8H, s, 4 ꢃ
NHCH2-Ar), 3.65 (8H, t, J 7.7, 4 ꢃ OCH2), 3.38 (8H, s,
Ar–CH2–Ar), 1.92–1.82 (8H, m, 4 ꢃ OCH2CH2), 1.06 (12H, t,
J 7.7, 4 ꢃ CH3).
5,17-Bis(N0-phenylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (partial cone) 9
To a stirred mixture of 139 mg (0.22 mmol) of 5,17-diamino-
24,25,26,27-tetrapropoxy-calix[4]arene (partial cone) in 4 ml of
dry dichloromethane 0.6 ml (5.6 mmol) phenyl isocyanate was
added to give a white precipitate. The mixture was stirred at
room temperature for 12 h, poured into methanol, stirred for
30 min and evaporated to dryness. The residue was dissolved
in chloroform and precipitated by methanol to yield 80 mg
(42%) of 9 as a yellowish powder, mp 290–293 1C (Found: C,
75.1; H, 7.0; N, 6.5. C54H60N4O6 requires C 75.32; H 7.02; N
6.51). dH (300 MHz; (CD3)2SO, Me4Si, 60 1C): 8.56 (1H, s,
NHCO), 8.49 (1H, s, NHCO), 8.33 (1H, s, NHCO), 8.08 (1H,
s, NHCO), 7.47 (4H, t, J 7,7, Ar-H), 7.35 (2H, s, Ar-H), 7.28
(2H, t, J 7.7, Ar-H), 7.27 (2H, t, J 7.7, Ar-H), 7.18 (2H, s, Ar-
H), 6.96 (1H, t, J 7.7, Ar-H), 6.95 (1H, t, J 7.7, Ar-H), 6.88
(2H, d, J 7.2, Ar-H), 6.40 (2H, t, J 7.2, Ar-H), 6.32 (2H, d, J
5,11,17,23-Tetrakis[(R)-(ꢁ)-1-(1-naphtyl)ethylureido]-
24,25,26,27-tetrapropoxycalix[4]arene (1,3-alternate) 12
To a stirred mixture of 100 mg (0.15 mmol) of 5,11,17,23-
tetraamino-24,25,26,27-tetrapropoxycalix[4]arene (1,3-alter-
nate) in 6 ml of dry dichloromethane 0.32 ml (1.83 mmol)
(R)-(–)-1-(1-naphtyl)ethyl isocyanate was added. The mixture
was stirred at room temperature for 12 h, poured into metha-
nol, stirred for 15 min and the white precipitate was filtered off
to yield 160 mg (73%) of compound 12, mp 307–308 1C
(Found: C, 76.5; H, 6.7; N, 7.8. C92H96N8O8 requires C
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76.64; H 6.71; N 7.77). dH (300 MHz; CDCl3–CD3OD 4 : 1,
Me4Si): 8.18 (4H, d, J 8.2, Ar-H), 7.87 (4H, d, J 8.8, Ar-H),
7.76 (4H, d, J 7.7, Ar-H), 7.55-7.42 (8H, m, Ar-H), 7.52
(8H, s, Ar-H), 6.93 (4H, s, Ar-H), 6.86 (4H, s, Ar-H), 5.78
(4H, q, J 6.6, CH), 3.55 (8H, t, J 7.2, 4 ꢃ OCH2), 3.38 (8H,
br s, Ar–CH2–Ar), 1.76–1.68 (8H, m, 4 ꢃ OCH2CH2),
1.64 (12H, d, J 7.2, 4 ꢃ CH3), 0.93 (12H, t, J 7.2, 4 ꢃ
CH2CH2CH3).
was monitored by TLC chromatography (petroleum
ether–chloroform 4 : 1). After 170 h the mixture was cooled,
poured into 80 ml of 1 M HCl and extracted with 4 ꢃ 30 ml of
chloroform. Combined extracts was washed by brine and
water and dried over magnesium sulfate. After filtration the
mixture was evaporated to dryness and separated on a
column of 40 g silica gel (petroleum ether–chloroform 8 : 1).
Finally, by preparative TLC chromatography (petroleum
ether–chloroform 10 : 1) 136 mg (26%) of compound 15 (RF
= 0.4) and 350 mg (67%) of compound 16 (RF = 0.9) were
obtained as yellow powders. 15: mp 229–232 1C (Found: C,
70.2; H, 6.5; N, 4.0. C40H46N2O8 requires C 70.36; H 6.79; N
4.10%). dH (300 MHz; CDCl3, Me4Si): 7.94 (4H, s, Ar-H), 7.01
(4H, d, J 7.7, Ar-H), 6.72 (2H, t, J 7.7, Ar-H), 3.69 (4H, t, J 7.7
Hz, 2 ꢃ OCH2), 3.64 (8H, s, Ar–CH2–Ar), 3.62 (4H, t, J 7.7, 2
ꢃ OCH2), 1.84–1.69 (8H, m, 4 ꢃ OCH2CH2), 1.00 (6H, t, J 7.2,
2 ꢃ CH3), 0.96 (6H, t, J 7.2, 2 ꢃ CH3). 16: mp 212–215 1C
(Found: C, 70.1; H, 6.7; N, 4.0. C40H46N2O8 requires C 70.36;
H 6.79; N 4.10%). dH (300 MHz; CDCl3, Me4Si): 8.22 (2H, s,
Ar-H), 8.03 (2H, s, Ar-H), 6.94 (2H, d, J 7.1, Ar-H), 6.48 (2H,
t, J 7.7, Ar-H), 6.27 (2H, d, J 7.3, Ar-H), 4.09 (2H, d, J 13.2,
Ar–CH2–Ar), 3.88 (2H, t, J 7.7, OCH2), 3.84–3.78 (2H, m,
OCH2), 3.79–3.67 (4H, m, Ar–CH2–Ar), 3.61–3.53 (2H, m,
OCH2), 3.39–3.34 (2H, m, OCH2), 3.18 (2H, d, J 13.7,
Ar–CH2–Ar), 1.43–1.31 (2H, m, OCH2CH2), 2.00–1.91 (6H,
m, 3 ꢃ OCH2CH2), 1.13 (6H, t, J 7.2, 2 ꢃ CH3), 1.11 (3H, t, J
7.2, CH3), 0.65 (3H, t, J 7.7, CH3).
5,17-Bis(N0-phenylureido)-24,25,26,27-
tetrapropoxycalix[4]arene (1,3-alternate) 13
To a stirred mixture of 70 mg (0.16 mmol) of 5,17-diamino-
24,25,26,27-tetrapropoxycalix[4]arene (1,3-alternate) in 4 ml of
dry dichloromethane 0.6 ml (5.6 mmol) of phenyl isocyanate was
added. The mixture was stirred at room temperature for 12 h,
poured into methanol, stirred for 30 min and evaporated to
dryness. The residue was separated on 40 g of silica gel
(petroleum ether–chloroform 2 : 1) and then by preparative
TLC chromatography (petroleum ether–ethyl acetate 10 : 1) to
yield 40 mg (42%) of compound 13 as a yellowish powder, mp
253–256 1C (Found C, 75.1; H, 7.0; N, 6.6. C54H60N4O6 requires
C 75.32; H 7.02; N 6.51%). dH (300 MHz; CDCl3, Me4Si): 7.89
(2H, br s, NHCO), 7.73 (4H, d, J 8.2, Ar-H), 7.36–7.28 (4H, m,
Ar-H), 7.09 (2H, t, J 7.2, Ar-H), 7.00 (4H, s, Ar-H), 6.98 (4H, d,
J 7.7, Ar-H), 6.59 (2H, t, J 7.2, Ar-H), 6.52 (2H, br s, NHCO),
3.67 (4H, t, J 7.2, 2 ꢃ OCH2), 3.66 (4H, t, J 7.2, 2 ꢃ OCH2), 3.47
(8H, s, Ar–CH2–Ar), 1.93-1.78 (8H, m, 4 ꢃ OCH2CH2), 1.10
(6H, t, J 7.7, 2 ꢃ CH3), 0.95 (6H, t, J 7.2, 2 ꢃ CH3).
Preparation of appropriate amino derivatives—general procedure
The procedure is adapted according to published proce-
dures:8,9 0.5 mmol of nitro derivative was mixed with n ꢃ
2.5 mmol of SnCl2ꢄ2H2O (n ꢃ 0.56 g, where n is the number of
nitro groups in the molecule of the starting calix[4]arene) and
dissolved in 30 ml of ethanol. The mixture was refluxed for
12 h, the solvent was then evaporated and the residue was
dissolved in a mixture of 30 ml of chloroform and 30 ml of 1 M
KOH. The organic layer was separated, and the aqueous layer
was extracted with 3 ꢃ 20 ml of chloroform. The extracts was
combined, dried over magnesium sulfate and evaporated to
dryness. The following amines were obtained.
5,17-Bis(N-benzoylamino)-24,25,26,27-
tetrapropoxycalix[4]arene (cone) 14
To a stirred solution of 100 mg (0.16 mmol) of 5,17-diamino-
24,25,26,27-tetrapropoxycalix[4]arene (cone) in 2 ml of dry
dichloromethane 0.05 ml (0.35 mmol) of triethyl amine and a
solution of 0.04 ml (0.35 mmol) of benzoyl chloride in 2 ml of
dry dichloromethane were added. The mixture was stirred at
room temperature for 12 h, poured into 10 ml of 1 M HCl and
extracted with 4 ꢃ 5 ml of chloroform. The organic layer was
washed with 5 ml of brine and water and a 10% solution of
potassium carbonate (to remove benzoic acid) and dried over
magnesium sulfate to yield 51 mg (40%) of title compound 14 as
a yellowish powder, mp 163–166 1C (Found: C, 77.9; H, 6.9; N,
3.4. C54H58N2O6 requires C 78.04; H 7.03; N 3.37%). dH (300
MHz; CDCl3, Me4Si): 7.62 (4H, m, Ar-H), 7.36 (2H, t, J 7.2, Ar-
H), 7.22 (4H, d, J 7.7, Ar-H), 6.83 (4H, s, Ar-H), 6.76 (4H, d, J
7.2, Ar-H), 6.66 (2H, t, J 6.6, Ar-H), 4.47 (4H, d, J 13.2,
Ar–CH2–Ar ax), 3.90 (4H, t, J 7.7, 2 ꢃ OCH2), 3.80 (4H, t, J
7.2, 2 ꢃ OCH2), 3.16 (4H, d, J 13.2, Ar–CH2–Ar eq), 1.97–1.88
(8H, m, 4 ꢃ OCH2CH2), 1.04–0.96 (12H, m, 4 ꢃ CH3).
5,11,17-Triamino-25,26,27,28-tetrapropoxycalix[4]arene (cone) 17
Yield: 214 mg (67%), dark yellow powder (Found: C, 75.2; H,
8.0; N, 6.5. C40H51N3O4 requires C 75.32; H 8.06; N 6.59%).
dH (300 MHz; CDCl3, Me4Si): 6.72 (2H, d, J 6.6, Ar-H), 6.65
(1H, t, J 6.6, Ar-H), 6.08 (2H, s, Ar-H), 6.00 (2H, s, Ar-H),
5.96 (2H, s, Ar-H), 4.40 (2H, d, J 13.7, Ar–CH2–Ar ax), 4.32
(2H, d, J 13.2, Ar–CH2–Ar ax), 3.85 (2H, t, J 7.2, 1 ꢃ OCH2),
3.73 (6H, t, J 7.2, 3 ꢃ OCH2), 3.64 (2H, m, NH2), 3.18 (4H, br
s, NH2), 3.05 (2H, d, J 13.2, Ar–CH2–Ar eq), 2.92 (2H, d, J
13.2, Ar–CH2–Ar eq), 1.91–1.84 (8H, m, 4 ꢃ OCH2CH2),
1.01–0.93 (12H, br t, J 7.7, 4 ꢃ CH3).
5,17-Dinitro-25,26,27,28-tetrapropoxycalix[4]arene
(1,3-alternate) 15 and 5,17-dinitro-25,26,27,28-
tetrapropoxycalix[4]arene (partial cone) 16
5,17-Diamino-25,26,27,28-tetrapropoxycalix[4]arene
A mixture of 0.46 g (0.83 mmol) of 5,17-dinitro-25,27-dipro-
poxycalix[4]arene-26,28-diol, 2.5 g (7.5 mmol) of caesium
carbonate and 0.8 ml (8.3 mmol) of propyl iodide were heated
to 70 1C in 40 ml of dry N,N-dimethylformamide. The reaction
(1,3-alternate) 18
Yield: 57 mg (from 0,1 mmol of nitro derivative, 92%), dark
yellow powder (Found: C, 77.0; H, 8.0; N, 4.4. C40H50N2O4
ꢀc
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requires C 77.14; H 8.09; N 4.50%). dH (300 MHz; CDCl3,
Me4Si): 6.98 (4H, d, J 7.7, Ar-H), 6.63 (2H, t, J 7.2, Ar-H),
6.47 (4H, s, Ar-H), 3.52 (8H, s, Ar–CH2–Ar), 3.50 (8H, m, 4 ꢃ
OCH2), 3.14 (4H, m, NH2), 1.78–1.62 (8H, m, 4 ꢃ OCH2C-
H2), 1.01 (6H, t, J 7.7, 2 ꢃ CH3), 0.95 (6H, t, J 7.7, 2 ꢃ CH3).
Dougheret and J. D. Kilburn, J. Chem. Soc., Perkin Trans. 1, 2002,
841; (i) P. A. Gale and P. D. Beer, Angew. Chem., Int. Ed., 2001, 40,
487; (j) Supramolecular Chemistry of Anions, ed. A. Bianchi, K.
Bowman-James and E. Garcia-Espana, Wiley-VCH, New York,
1997; (k) F. P. Schmidtchen and M. Berger, Chem. Rev., 1997, 97,
1609.
2 (a) B. J. Hay, T. K. Firman and B. A. Moyer, J. Am. Chem.
Soc., 2005, 127, 1810; (b) C. R. Bondy and S. J. Loeb, Coord.
Chem. Rev., 2003, 240, 77; (c) K. Choi and A. D. Hamilton, Coord.
Chem. Rev., 2003, 240, 101; (d) P. D. Beer, A. G. Cheetham,
M. G. B. Drew, O. D. Fox, E. J. Hayes and T. D. Rolls, Dalton
Trans., 2003, 603.
5,17-Diamino-25,26,27,28-tetrapropoxycalix[4]arene (partial
cone) 19
Yield: 215 mg (69%), dark yellow powder (Found: C, 77.0; H,
8.0; N, 4.4. C40H50N2O4 requires C 77.14; H 8.09; N 4.50%).
dH (300 MHz; CDCl3, Me4Si): 6.92 (2H, d, J 7.2, Ar-H), 6.57
(2H, s, Ar-H), 6.48 (2H, s, Ar-H), 6.43 (2H, t, J 7.7, Ar-H),
6.36 (2H, d, J 7.7, Ar-H), 4.02 (2H, d, J 13.2, Ar–CH2–Ar),
3.77–3.68 (2H, m, OCH2), 3.69 (2H, t, J 7.7, OCH2), 3.55 (2H,
s, Ar–CH2–Ar), 3.53 (2H, s, Ar–CH2–Ar), 3.51 (2H, t, J 7.7,
OCH2), 3.38 (4H, br s, NH2), 3.33–3.27 (2H, m, OCH2), 2.92
(2H, d, J 13.2, Ar–CH2–Ar), 1.93–1.82 (4H, m, 2 ꢃ OCH2C-
H2), 1.59–1.51 (4H, m, 2 ꢃ OCH2CH2), 1.09 (6H, t, J 7.7, 2 ꢃ
CH3), 1.04 (3H, t, J 7.2, CH3), 0.78 (3H, t, J 7.2, CH3).
3 For books on calixarenes see: (a) Calixarenes 2001, ed. Z. Asfari,
V. Bohmer, J. Harrowfield and J. Vicens, Kluwer Academic
¨
Publishers, Dordrecht, 2001; (b) L. Mandolini and R. Ungaro,
Calixarenes in Action, Imperial College Press, London, 2000; (c) C.
D. Gutsche, Calixarenes Revisited, Monographs in Supramolecu-
lar Chemistry, ed. J. F. Stoddart, The Royal Society of Chemistry,
Cambridge, 1998, vol. 6; (d) Calixarenes 50th Anniversary: Com-
memorative Issue, ed. J. Vicens, Z. Asfari and J. M. Harrowfield,
Kluwer Academic Publishers, Dordrecht, 1994; (e) Calixarenes: A
Versatile Class of Macrocyclic Compounds, ed. J. Vicens and V.
Bohmer, Kluwer Academic Publishers, Dordrecht, 1991.
¨
4 (a) A. Casnati, F. Sansone and R. Ungaro, Calixarene Receptors in
Ion Recognition and Sensing, in Advances in Supramolecular
Chemistry, ed. G. W. Gokel, Cerberus Press Inc., South Miami,
2004, pp. 169–218, vol. 9; (b) P. Lhotak, Anion Receptors Based on
´
Crystallography. C54H60N4O6ꢄC2H5OHꢄH2O 19,
M =
Calixarenes, Top. Curr. Chem., 2005, 255, 65–96, and references
therein; (c) A. V. Yakovenko, V. I. Boyko, V. I. Kalchenko, L.
Baldini, A. Casnati, F. Sansone and R. Ungaro, J. Org. Chem.,
2007, 72, 3223; (d) B. Schazmann and D. Diamond, New J. Chem.,
2007, 31, 587–592.
5 (a) P. A. Gale, Coord. Chem. Rev., 2003, 240, 191; (b) M. M. G.
Antonisse and D. N. Reinhoudt, Chem. Commun., 1998, 443.
´ ´
6 (a) I. Stibor, S. M. H. Dana, P. Lhotak, J. Hodacova, J. Koca and
931.23 g molꢁ1, orthorhombic system, space group P212121,
a = 15.2889(2), b = 17.4579(3), c = 18.7828(4) A, Z = 4,
V = 5013.36(10) A3, Dc = 1.14 g cmꢁ3, m(Mo-Ka) = 0.074
mmꢁ1, crystal dimensions of 0.3 ꢃ 0.5 ꢃ 0.3 mm. Data were
collected at 150(2) K on a Nonius KappaCCD diffractometer
with graphite monochromated Mo-Ka radiation. The struc-
ture was solved by direct methods18 using the CRYSTALS
suite of programs19 and anisotropically refined by full-matrix
least squares on F values to final R = 0.0397 and Rw = 0.0474
using 6300 independent reflections (ymax = 27.471) and 649
parameters. The positions of disordered groups were found
from the electron density maps. Disordered fragments were
then placed in appropriate positions, and all distances between
neighbouring atoms and angles were fixed. Site occupancies
were refined for the different parts with the same thermal
parameters for the same atoms in the various fragments. At
the end of refinement, site occupancies were fixed and hydro-
gen atoms were placed in calculated positions.
M. Cajan, Gazz. Chim. Ital., 1997, 127, 673; (b) M. Cajan, I. Stibor
and J. Koca, J. Phys. Chem. A, 1999, 103, 3778; (c) M. Cajan, J.
Damborsky
40, 1151; (d) I. Stibor, R. Holakovsky
Lhotak, Collect. Czech. Chem. Commun., 2004, 69, 365; (e) J. Budka,
P. Lhotak, V. Michlova and I. Stibor, Tetrahedron Lett., 2001, 42,
1583; (f) V. Stastna, P. Lhotak, V. Michlova, I. Stibor and J. Sykora,
Tetrahedron, 2002, 58, 7207; (g) M. Dudic, P. Lhotak, I. Stibor, K.
Lang and P. Proskova, Org. Lett., 2003, 5, 149; (h) P. Lhotak, J.
Svoboda, Jr and I. Stibor, Tetrahedron, 2006, 62, 1253.
´
, I. Stibor and J. Koca, J. Chem. Inf. Comput. Sci., 2000,
´
, A. M. Mustafina and P.
´
´
´
´
´
´
´
´
´
7 (a) W. Verboom, S. Datta, Z. Asfari, S. Harkema and D. N.
Reinhoudt, J. Org. Chem., 1992, 57, 5394; (b) A. Casnati, F.
Bonetti, F. Sansone, F. Ugozzoli and R. Ungaro, Collect. Czech.
Chem. Commun., 2004, 69, 1063.
8 G. Mislin, E. Graf and M. W. Hosseini, Tetrahedron Lett., 1996,
37, 4503.
9 A. M. A. van Wageningen, E. Snip, W. Verboom, D. N. Reinhoudt
and H. Boerrigter, Liebigs Ann., 1997, 2235.
10 P. Timmerman, H. Boerrigter, W. Verboom and D. N. Reinhoudt,
Recl. Trav. Chim. Pays-Bas, 1995, 114, 103.
CCDC reference number 678255. For crystallographic
data in CIF or other electronic format see DOI: 10.1039/
b802871k
11 O. Struck, L. A. J. Chrisstoffels, R. J. W. Lugtenberg, W.
Verboom, G. J. van Hummel, S. Harkema and D. N. Reinhoudt,
J. Org. Chem., 1997, 62, 2487.
12 S. E. Matthews, M. Saadioui, V. Bohmer, S. Barboso, F. Arnaud-
¨
Neu, M.-J. Schwing-Weill, A. G. Carrera and J.-F. Dozol, J.
Prakt. Chem./Chem.-Ztg., 1999, 341, 264.
Acknowledgements
This work was partly supported by the Czech Science Founda-
tion (grants No: 203/06/1796 and 203/06/0738), Grant Agency
of the Academy of Sciences of the Czech Republic (IAA
400720706), and by MSMT grants (No. 223100001 and OC134).
13 R. K. Castellano and J. Rebek, Jr, J. Am. Chem. Soc., 1998, 120,
3657.
14 The stoichiometry of complexes and the complexation
constants were calculated using the computer program OPIUM
(M. Kyvala) freely available at http://www.natur.cuni.cz/Bkyvala/
opium.html.
15 For leading references of aromatic stacking interactions, see:
(a) C. A. Hunter, K. R. Lawson, J. Perkins and C. J. Urch, J.
Chem. Soc., Perkin Trans. 2, 2001, 651; (b) S. L. Cockkroft,
J. Perkins, C. Zontaq, H. Adams, S. E. Spey, C. M. R. Low,
J. G. Winter, K. R. Lawson, C. J. Urch and C. A. Hunter, Org.
Biomol. Chem., 2007, 5, 1062; for interaction of halide anions
with electron deficient arenas, see: O. B. Berryman, V. S.
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