Anion recognition by diureido-calix[4]arenes in the 1,3-alternate conformation

Article abstract of DOI:10.1039/b816790g

A series of diureido-calix[4]arenes immobilised in the 1,3-alternate conformation was synthesised and systematically studied for their complexation ability. As revealed by ¹H NMR and UV/vis titrations, this structural motif leads to very effici

Full text of DOI:10.1039/b816790g

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Anion recognition by diureido-calix[4]arenes in the 1,3-alternate
conformationw
ab
a
a
b
c
ˇ
Petra Curınova, Ivan Stibor,* Jan Budka, Jan Sykora, Kamil Lang
´ ´
´
a
´
and Pavel Lhotak*
Received (in Durham, UK) 25th September 2008, Accepted 20th November 2008
First published as an Advance Article on the web 15th January 2009
DOI: 10.1039/b816790g
A series of diureido-calix[4]arenes immobilised in the 1,3-alternate conformation was synthesised
1
and systematically studied for their complexation ability. As revealed by H NMR and UV/vis
titrations, this structural motif leads to very efficient ligands for anion recognition with high
binding constants in nonpolar solvents. The comparison with the corresponding ligands
possessing the cone conformation indicates that diureido-calix[4]arene in a 1,3-alternate
conformation are very promising anion receptors with pronounced binding ability towards
carboxylates.
Calix[4]arenes are frequently used in the role of molecular
Introduction
scaffolds, as they are versatile macrocyclic compounds with
tuneable 3D-shapes of their skeleton, well established
chemistry, and abundant literature resources.3 Many neutral
calixarene-based ligands designed for binding of anions4 or
cation–anion couples5 have been described so far. Our own
research has been oriented to anion recognition using simple
(hetero)aromatic amides,6a–c ureas,6d or calixarene-based
ligands.6e–i Recently, we have described a series of new bis-
to tetrakis-(ureido)calix[4]arenes in the cone conformation6j
and we have demonstrated that these compounds can be
extremely efficient ligands for complexation of anions
possessing different binding geometries. Here we report on
the synthesis and complexation ability of ureido-calix[4]arenes
having two arylurea units appended to the upper rim of the
calix[4]arene skeleton. Immobilisation in the 1,3-alternate
conformation can make these derivatives even more efficient
when compared with the corresponding cone analogues as
documented by extremely high binding constants in nonpolar
solvents.
The importance of anions in biological systems, chemical
processes, or environmental pollution is well recognised. For
this reason, the anion recognition plays an important role in
supramolecular chemistry as can be documented by numerous
reviews published recently.1 In the design of novel anion-
complexing ligands the three main strategies have been
developed: (i) ligands using electrostatic interactions with
anions (cationic, polyammonium, quanidinium, quaternary
ammonium, porphyrin-based ligands); (ii) neutral ligands
based on the variety of Lewis-acids (derivatives bearing tin,
silicon, boron, mercury, uranyl, or other metal moieties); and
(iii) neutral ligands allowing hydrogen bonding interactions.
Not surprisingly, considerable effort has been devoted to the
design of the last group of receptors, as neutral organic ligands
with hydrogen bonding functionalities possess some remark-
able advantages.2 Neutral receptors are usually pH insensitive
and there is generally no competition with a counter anion as
contrast to the protonated anion receptors from the group
(i). Furthermore, it is known that anionic species have a wide
range of geometries depending on the nature of anion.
Correspondingly, the design of anionic receptors is especially
challenging when compared with those for cations because
the successful binding of anions requires higher degree of
preorganisation, interaction directionality, and complemen-
tarity. Neutral ligands can thus benefit from the anisotropy of
hydrogen bonding and can be used for the construction of
highly preorganised and selective anion receptors.
Results and discussion
Design
The systematic study of neutral ligands based on ureido-
calixarenes for anion recognition revealed that tetrapropoxy-
calix[4]arene bearing two ureido moieties on the upper rim is
the versatile structural motif with an excellent ability to bind
anions.6j To our surprise, ligand 2 in the 1,3-alternate
conformation showed better affinity towards anions than
corresponding cone derivative 1 indicating that the 1,3-
alternates represent a promising conformation in the design
of novel anion receptors. Based on this finding we have
designed a series of six receptors 7–12 in the 1,3-alternate
conformation (Fig. 1). As we have encountered some problems
with a low solubility of derivative 2,6j we introduced two hexyl
groups to enhance the solubility in common organic solvents.
The propyl groups on the ‘‘ureido-side’’ of the scaffold are
a Department of Organic Chemistry, Institute of Chemical Technology,
Technicka 5, 166 28 Prague 6, Czech Republic.
E-mail: Ivan.Stibor@vscht.cz. E-mail: Pavel.Lhotak@vscht.cz;
Fax: +420-220444280; Tel: +420-220444288
b Institute of Chemical Process Fundamentals, v.v.i., Academy of
´
Sciences of the Czech Republic, Rozvojova 135, 165 02 Prague 6,
Czech Republic
c Institute of Inorganic Chemistry, v.v.i, Academy of Sciences of the
ˇ
Czech Republic, 250 68 Rezˇ, Czech Republic
w CCDC reference number 698241. For crystallographic data in CIF
or other electronic format see DOI: 10.1039/b816790g
ꢀc
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Fig. 1 Prepared urea derivatives of calix[4]arene.
necessary for the ‘‘freezing’’ of the conformation and our
Complexation
previous results did not show steric hindrance effects for the
binding of anions. The group R in formulae 7–12 stands for
different substituents used to evaluate the structure-complexation
ability relationship. Thus, phenyl (7), benzyl (8), phenyl-
sulfonyl (9), benzoyl (10), chloroacetyl (11) and p-nitrophenyl
(12) groups were used.
The complexation behaviour of novel ligands was investigated
1
by standard H NMR titration experiments using a constant
calixarene concentration (0.1–2.0 mM) and an increasing
concentration of appropriate anion to obtain different
host : guest ratios (0.1–20 : 1).6e To ensure the solubility of
both organic (ligands) and inorganic (anions) constituents, a
mixed solvent system (CDCl3–CD3CN = 4 : 1, v/v) was used.
All anions were added as their tetrabutylammonium salts to
minimise possible interactions of calixarenes with counter
cations. The addition of anions led to the down-field shifts
of –NH– signals in the 1H NMR spectra indicating the
complexation phenomenon under fast exchange conditions.
Unfortunately, the signals of –NH– protons became
broadened (and sometimes even completely disappeared),
hence, the binding constants were determined from the
complexation induced shifts (CIS) of neighbouring aromatic
CH protons (meta-positions). These shifts were usually
20–50 Hz upon the addition of 2.5 equivalents of anions.
Fig. 3 shows a typical binding isotherm indicating the forma-
tion of a 1 : 1 complex. The stoichiometry of the complexation
was also confirmed by the corresponding Job plots. The results
Synthesis
The compounds 7–12 were prepared using a similar procedure
as reported for compound 2.6j In general, the whole synthetic
pathway can be described by the sequence: (i) alkylation of
starting calix[4]arene to 25,27-dipropoxycalix[4]arene,7a,b
(ii) nitration to 5,17-dinitro-25,27-dipropoxycalix[4]arene,7c,d
(iii) subsequent alkylation with hexyl iodide to 5,17-dinitro-
26,28-dihexyloxy-25,27-dipropoxycalix[4]arene, (iv) reduction
to 5,17-diamino-derivative, (v) reaction with aryl isocyanate to
form appropriate bis(ureido)-calix [4]arenes 7–12 (Fig. 2).
Nitration of dipropoxycalix[4]arene using a well established
procedure8 led regioselectively to the corresponding dinitro
derivative 3 with p-nitrated free phenolic rings. Subsequent
alkylation to corresponding 1,3-alternate 4 is a key step, and at
the same time the bottle-neck of the whole reaction sequence.
The best yield was achieved using similar reaction conditions
as applied for the preparation of derivative 2.6j Alkylation of
dipropoxy derivative 3 with hexyl iodide in DMF using
caesium carbonate as a base led to a mixture of two
conformers 4 and 5 in 17 and 70% yields, respectively.
Unfortunately, despite our substantial effort, the variations
in the base, solvent, and reaction temperature did not improve
yields of the 1,3-alternate 4, and the unwished partial cone
conformation 5 was always the main product. The separation
of these two conformers can be achieved only by column
chromatography which makes the synthesis of pure 4 some-
what laborious despite the great difference in the chromato-
obtained are summarised in Table
1 where previously
described compound 1 has been taken as a reference.6j
The binding constants of novel receptors 7, 9 and 12 towards
some anions were too large to be measured accurately by
1H NMR spectroscopy and the values given are rough
estimations.
As follows from Table 1, the 1,3-alternate calix[4]arene-
based ureas are very effective receptors for anions in organic
solvent, especially, when the structural motif based on
aromate-urea-aromate is constructed. A direct comparison
of otherwise identical ligands 1 and 7 (possessing different
conformations) indicates that the 1,3-alternate conformation
(compound 7) leads to much higher complexation constants if
compared with the cone receptor 1. This phenomenon can be
ascribed to the higher rigidity of a 1,3-alternate conformation
compared with the cone analogue. It is known that in the case
of the cone conformers so-called pinched cone–pinched cone
equilibrium12 occurs in solution, and these additional confor-
mational movements should be generally unfavourable for
4
5
graphic mobility of both isomers (RF = 0.3 and RF = 0.9).
The pure 1,3-alternate isomer 4 was then reduced by SnCl2
dihydrate in ethanol7d,9,10 to give the corresponding 1,3-alternate
derivative 6 in 89% yield. The synthesis of 7–12 was finally
achieved in 40–60% yields using
a standard reaction
protocol11 with commercially available isocyanates.
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Fig. 2 Synthetic pathway to anion receptors 7–12.
The insertion of one –CH2– group between the urea
moiety and the aromatic calix[4]arene core in 8 causes a
dramatic decrease in the complexation ability (compare
KCl = 5 ꢁ 104
M
ꢂ1, KBr = 8 ꢁ 103 Mꢂ1 for 7 vs. KCl
=
1300 Mꢂ1, KBr = 930 Mꢂ1 for 8). When the aromatic ring is
connected to the urea moiety via the electron-withdrawing
sulfonyl group (ligand 9), the complexation abilities towards
anions increased.
On the other hand, compound 10 with the electron-
withdrawing carbonyl group as a spacer showed only negli-
gible changes in the 1H NMR spectra upon the addition of
anions. This unexpected difference in the behaviour of struc-
turally related compounds 9 and 10 can be explained by the
analysis of the crystallographic results. It was revealed that
compound 10 forms very strong intramolecular hydrogen
bonds between –NH– and –CO– groups in the solid state as
shown in Fig. 4. The Hꢃ ꢃ ꢃO distances are 1.87 and 1.91 A. The
similar hydrogen bonding pattern was found in the crystal
Fig. 3 Binding isotherm of ligand 7 with BzOꢂ anion.
the complexation phenomenon. On the other hand, no similar
additional mobility was observed in the 1,3-alternate
derivatives.
Table 1 Binding constants of ligands 7–12 towards selected anions (1H NMR titration, 300 MHz, CDCl3–CD3CN = 4 : 1, v/v, 25 1C)
K/Mꢂ1
Anion
16j
7
8
9
10
11
12
a
Chloride
Bromide
Acetate
4700 ꢄ 490
50 000 ꢄ 9000
8000 ꢄ 1200
35 000 ꢄ 6000
4106
1300 ꢄ 160
930 ꢄ 200
105
110 ꢄ 10
4106
—
1400 ꢄ 160
3500 ꢄ 450
—
80 ꢄ 20
3900 ꢄ 200
800 ꢄ 100
a
4000 ꢄ 1100
5700 ꢄ 180
6000 ꢄ 1100
105
80 000 ꢄ 10 000
Benzoate
(1.6 ꢄ 0.45) ꢁ 105
4106
1700 ꢄ 200
4106
a
No visible changes (CIS o5 Hz).
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Table 2 Binding constants K/Mꢂ1 of receptor 12 with selected anions
(UV/Vis titration, CH2Cl2, 298 K)
Aniona
K/Mꢂ1
Clꢂ
Brꢂ
Iꢂ
2.8 ꢁ 107 b
1.9 ꢁ 105
3.9 ꢁ 105
5 ꢁ 107 b
4106
ꢂ
NO3
BzOꢂ
a
Anions were added as tetrabutylammonium salts. Estimated error is
b
15%. A larger standard deviation (35%) is due to almost linear
titration curves causing ill-effects during the least-squares fitting
procedure.
Fig. 4 Intramolecular hydrogen bonding pattern in the crystal struc-
ture of ligand 10 (other hydrogen atoms are omitted for better clarity).
structures of simple acylureido derivatives.13 The intra-
molecular hydrogen bonding is highly probable even in solution
1
as documented by the comparison of H NMR spectra. The
signals of –NH– protons in 7 are at 7.91 and 6.46 ppm, while
the same signals in 10 can be found at 10.92 and 10.49 ppm.
The pronounced low-field shift in compound 10 indicates
strong intramolecular hydrogen bonding that might be
responsible for the negligible complexation ability of ligand
10. Furthermore, compound 10 forms an interesting dimeric
motif in the solid state where two molecules are interconnected
via four intermolecular hydrogen bonds (Fig. 5).
Fig. 6 UV/Vis titration of 12 (2.7 ꢁ 10ꢂ5 M) with benzoate in
CH2Cl2; arrows show changes due to increasing concentration of
10ꢂ3 M. Inset: the corresponding Job
In ligand 11, the aliphatic chain is attached to the urea
moiety. Although the complexation ability of this receptor is
generally reduced compared to its aromatic analogue 7, an
exceptional selectivity towards acetate was observed.
benzoate up to 2.1
ꢁ
plot documenting the 1 : 1 stoichiometry of the complex. The plot
was constructed from absorbance changes at 375 nm using the sum of
concentrations 3.2 ꢁ 10ꢂ5 M.
As the p-nitrophenyl group is
a chromophore, the
complexation properties of 12 were complemented using
UV/Vis titration experiments (Table 2, Fig. 6).17 The increasing
amount of anions led to a red shift of the p-nitrophenyl
absorption band and the obtained set of recorded absorption
spectra was globally analyzed to obtain the corresponding
binding constants. The interaction between –NH and anions is
much stronger when compared to the structurally equivalent
calix[4]arenes 1 and 7 (Tables 1 and 2) since the nitro group
makes the benzene ring electron deficient thus increasing the
hydrogen bond donating capability of the N–H groups. Our
results also demonstrate that 12 isꢂan effective binder even for
non-spherical anions such as NO3 and BzOꢂ.
Compound 12 binds strongly Clꢂ, Brꢂ and BzOꢂ so that the
binding isotherms exhibit a sharp saturation beyond the molar
concentration ratio of 1 : 1 indicating the stoichiometry 1 : 1
and the binding constants above 106 Mꢂ1. The stoichiometry
of complexes was confirmed by Job plot analysis. Thus, the
binding isotherms, the observed isosbestic points, and corres-
ponding Job plots clearly indicate that a 1 : 1 complex is
formed between 12 and anions (Fig. 6). The binding site is
created by two diametrically placed ureas that offer four
hydrogen-bonding interactions for the binding of anions in
between. The importance of multipoint interactions on the
efficiency of the binding follows clearly from the comparison
of 12 with model calixarene bearing only one nitrophenyl-urea
Fig. 5 Dimeric motif in the crystal packing of ligand 10 connected via
intermolecular hydrogen bonds (other hydrogen atoms and propyl
groups are omitted for better clarity).
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Experimental
Melting points were determined on a Boetius block apparatus
(Carl Zeiss Jena, Germany) and are not corrected. All 1H
NMR and 13C NMR measurements were performed in 5 mm
o.d. sample tubes and were recorded on a Varian Gemini
300 or Varian Mercury 300, using tetramethylsilane as an
internal standard. Mass spectra were measured using the ESI
technique on a Q-TOF (Micromass) spectrometer or the
MALDI-TOF technique on an HP G2030A (Hewlett Packard)
with a delayed extraction option. All UV/vis spectra were
measured on a PerkinElmer Lambda 35 spectrometer. Crystal
structures were determined by X-ray crystallography, data
were collected on an Enraf Nonius CAD4 diffractometer with
graphite monochromated Cu-Ka radiation at 293 K.
The crystal structures presented in this paper were created
using the Platon for Windows14 and POV-Rayt for Windows,
version 3.6.
Fig. 7 Absorption spectra of 12 (a), 12-BzOꢂ (b) and 12-(BzOꢂ)2 (c)
in CH2Cl2. The absorption spectrum of 12-(BzOꢂ)2 was obtained
using 3.60 ꢁ 10ꢂ5 M 12 and 0.142 M BzOꢂ.
Dichloromethane used for the reactions was dried with
CaH2, and stored over 4 A molecular sieves. The purity of
the substances and the courses of reactions were monitored by
TLC using TLC aluminum sheets with silica gel 60 F254
(Merck). Preparative TLC chromatography was carried out
on 20 ꢁ 20 cm glass plates covered by silica gel 60 GF254
(Merck). All chemicals from Aldrich, Fluka, Merck, Lancaster
and Across Organics with 99% and higher purity were used
without further purification.
arm.18 The presence of two ureido functions in 12 strengthen
ꢂ
the binding constant for planar NO3 anion by two orders of
magnitude from 6.9 ꢁ 103 Mꢂ1 (model) to 3.9 ꢁ 105 Mꢂ1
(receptor 12).
The spectral features of complexes allow distinguishing the
binding mode of anions, i.e., if anion is bound by four
(between two ureas) or two (two hydrogens of one urea)
hydrogen-bonding interactions. For example, the strong inter-
action of 12 (band at 333 nm, 3.1 ꢁ 104 Mꢂ1 cmꢂ1) with
benzoates leads to a 1 : 1 complex characterized by the
absorption band at 363 nm (Fig. 6 and 7(b)) where BzOꢂ
interacts with the preorganised binding site of two ureas. At
large excess of BzOꢂ the absorption band of the 1 : 1 complex
further moves to longer wavelengths (i.e., to 377 nm) indicat-
ing the transformation of the 1 : 1 stoichiometry to 1 : 2 where
each urea of 12 binds BzOꢂ separately (Fig. 7(c)). This
interpretation is corroborated by the spectral features
of calixarene bearing only one urea-nitrophenyl arm18
(two hydrogen bonding interactions are available): the original
absorption band at 330 nm shifts to 380 nm upon forming the
1 : 1 complex with BzOꢂ, i.e. it has the similar position as the
band of 12ꢃ(BzOꢂ)2.
26,28-Dihexyloxy-5,17-dinitro-25,27-dipropoxy-calix[4]arene
(1,3-alternate) 4 and (partial cone) 5
5,17-dinitro-25,27-dipropoxycalix[4]arene-26,28-diol 3 (1 g,
1.67 mmol) was stirred in anhydrous DMF (50 ml) with
Cs2CO3 (3.84 g, 0.0118 mol). Then hexyl iodide (1.74 ml,
11.8 mmol) was added and the reaction mixture was heated to
110 1C for 5 days. The mixture was then spoiled into 1M HCl
and extracted with chloroform. Traces of iodine were removed
by washing with 20% Na2SO3 and organic layer was dried
over anhydrous magnesium sulfate. The solvents were
removed in vacuo and the crude mixture was resolved by
column chromatography by CH2Cl2: petroleum ether 3 : 1
(v/v) as eluent. 26,28-Dihexyloxy-5,17-dinitro-25,27-dipro-
poxycalix[4]arene (1,3-alternate) 4 (RF = 0.3) was obtained
as yellowish powder in 17% yield (0.27 g), mp 152–155 1C.
Found: C, 72.0; H, 7.6; N, 3.6 (C46H58N2O8 requires C 72.04;
Conclusions
1
H 7.62; N 3.65). H NMR (300 MHz; CDCl3, 296 K): d 7.82
Effective anion receptors 7–12 were obtained by the
attachment of two urea moieties into the para positions of
calix[4]arene immobilised in the 1,3-alternate conformation.
The substituents on the urea moiety heavily influence
the binding ability of receptors. The presence of electron
withdrawing groups (receptors 9 and 12) results in very
high binding affinity towards anions. The structural motif
‘‘aromate-urea-aromate’’ combined with the 1,3-alternate
conformation of the calix[4]arene skeleton proved to be
very useful in design of novel anion receptors. The inter-
dependence between the binding affinity and structural char-
acteristics of binding sites provides a rational basis for the
design and creation of novel receptors systems for molecular
recognition.
(4H, s, Ar–H), 6.92 (4H, d, J 7.4, Ar–H), 6.64 (2H, t, J 7.4,
Ar–H), 3.62–3.51 (16H, m, O–CH2 + Ar–CH2–Ar), 1.66–1.58
(8H, m, 4 ꢁ CH2), 1.28 (12H, m, 6 ꢁ CH2), 0.88 (12H, m,
4 ꢁ –CH3); 13C NMR (75 MHz; CDCl3, 296 K): d 161.8,
156.0, 141.4, 134.4, 132.3, 130.1, 125.1, 121.9, 73.7, 72.7, 35.9,
31.6, 30.2, 25.4, 23.2, 22.5, 13.9 and 10.1; TOF-MS ESI+
required 766.4 for C46H58N2O8, found: 789.6 [M + Na]+
(100%).
Partial cone analogue 5 (RF = 0.9) was obtained as yellowish
microcrystals in 70% yield (1.11 g), mp 158–1601 C. Found:
C, 71.9; H, 7.6; N, 3.6 (C46H58N2O8 requires C 72.04; H 7.62;
1
N 3.65). H NMR (300 MHz; CDCl3, 296 K): d 8.22 (2H, s,
Ar–H), 8.03 (2H, s, Ar–H), 6.92 (2H, d, J 6.7, Ar–H), 6.47
(2H, t, J 7.4, Ar–H), 6.25 (2H, d, J 7.0, Ar–H), 4.11 (2H, d,
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J 12.9, Ar–CH2–Ar), 3.90 (2H, t, J 7.2, O–CH2), 3.84–3.65
(6H, m, 2 ꢁ O–CH2 + Ar–CH2–Ar), 3.58 (2H, t, J 7.2,
O–CH2), 3.44 (2H, t, J 7.7, O–CH2), 3.19 (2H, d, J 13.5,
Ar–CH2–Ar), 2.02–1.93 (6H, m, 3 ꢁ O–CH2–CH2), 1.54–1.46
(2H, m, O–CH2–CH2), 1.44–1.32 (6H, m, 3 ꢁ CH2), 1.24–1.31
(2H, m, CH2), 1.23–1.14 (2H, m, CH2), 1.12 (6H, t, J 7.2,
2 ꢁ –CH3), 1.07–0.96 (2H, m, CH2), 0.95 (3H, t, J 7.2, –CH3),
0.89 (3H, t, J 7.7, –CH3); 13C NMR (75 MHz; CDCl3, 296 K):
d 163.7, 156.0, 142.9, 142.5, 138.4, 135.5, 132.5, 131.4, 129.9,
129.3, 126.2, 124.8, 122.5, 76.8, 75.0, 74.3, 35.4, 31.6, 31.2,
30.7, 30.5, 28.7, 25.6, 24.9, 23.6, 22.7, 22.5, 13.8, 13.7 and 10.6;
TOF-MS ESI+ required 766.4 for C46H58N2O8, found: 789.4
[M + Na]+ (100%).
131.3, 130.1, 129.1, 124.5, 123.3, 122.4, 119.8, 75.6, 73.6, 35.3,
32.1, 30.7, 26.1, 24.2, 22.9, 14.3, 10.8; TOF-MS ESI+ required
944.6 for C60H72N4O6, found: 967.5 [M + Na]+ (100%).
5,17-Bis(N0-benzylureido)-26,28-dihexyloxy-25,27-dipropoxy-
calix[4]arene (1,3-alternate) 8
The crude product was purified by preparative TLC
(CHCl3–ethyl acetate 15 : 1) to obtain pure compound 8 as
a white powder in 63% yield, mp 246–248 1C. Found: C, 76.4;
H, 7.8; N, 5.7 (C62H76N4O6 requires C 76.51; H 7.87; N 5.76);
1H NMR (300 MHz; CDCl3, 296 K): d 7.36–7.28 (10H, m,
ArH), 6.96 (4H, d, J 7.4, Ar–H), 6.91 (4H, s, Ar–H), 6.57
(2H, t, J 7.5, Ar–H), 6.28 (2H, s, NH), 6.06 (2H, t, CH2–NH),
4.50 (4H, d, J 5.8, CH2–NH), 3.70–3.28 (8H, m, O–CH2–),
3.44 (8H, m, Ar–CH2–Ar), 1.91–1.83 (8H, m, 4 ꢁ CH2),
1.58–1.40 (12H, m, 6 ꢁ CH2), 1.05 (6H, t, J 7.1, 2 ꢁ CH3),
0.96 (6H, t, J 6.9, 2 ꢁ CH3); 13C NMR (75 MHz; CDCl3,
296 K): d 157.1, 155.7, 153.5, 139.2, 134.9, 133.4, 131.5, 130.0,
128.7, 127.6, 127.3, 124.4, 122.2, 75.5, 73.6, 44.2, 35.2, 32.1,
30.7, 26.1, 24.1, 22.9, 14.3, 10.9; TOF-MS ESI+ required
972.6 for C62H76N4O6, found: 995.6 [M + Na]+ (100%),
973.5 [M + H]+ (30%).
5,17-Diamino-26,28-dihexyloxy-25,27-dipropoxy-calix[4]arene
(1,3-alternate) 6
Dinitro-derivative 4 (0.27 g, 0.35 mmol) was dispersed in 25 ml
of ethanol. Then SnCl2ꢃ2H2O (0.79 g, 3.5 mmol) was added
and the mixture was heated to reflux overnight. Solvent was
evaporated, the residue was taken up with chloroform and
poured into 1 M KOH. The product was extracted into
chloroform, combined organic layers were washed once with
brine and then evaporated to dryness, yielding 0.22 g of 6
(89%), mp 83–851 C. Found: C, 78.1; H, 8.8; N, 4.0
(C46H62N2O4 requires C 78.15; H 8.84; N 3.96). 1H NMR
(300 MHz; CDCl3, 296 K): d 7.26 (4H, s, NH2), 6.97 (4H, d,
J 7.4, Ar–H), 6.63 (2H, t, J 7.4, Ar–H), 6.49 (4H, s, Ar–H),
3.55–3.50 (16H, m, O–CH2 + Ar–CH2–Ar), 1.72 (4H, m,
2 ꢁ CH2), 1.61 (4H, m, 2 ꢁ CH2), 1.35 (12H, m, 6 ꢁ CH2),
1.01 (6H, t, 2 ꢁ –CH3), 0.88 (6H, t, 2 ꢁ –CH3); 13C NMR
(75 MHz; CDCl3, 296 K): d 156.4, 149.9, 140.9, 134.4, 133.8,
129.8, 121.7, 117.8, 74.8, 73.3, 36.3, 32.2, 30.4, 26.0, 23.8, 22.9,
14.8, 11.9; TOF-MS ESI+ required 706.5 for C46H62N2O4,
found: 729.7 [M + Na]+ (100%).
5,17-Bis[N0-(phenylsulfonyl)ureido]-26,28-dihexyloxy-25,27-
dipropoxycalix[4]arene (1,3-alternate) 9
The crude product was purified by column chromatography
(CH2Cl2–ethyl acetate 5 : 1). The product 9 was obtained as a
yellowish solid in 66% yield, mp 215–217 1C. Found: C, 67.1;
H, 6.6; N, 5.1; S 5.9 (C60H72N4O10S2 requires C 67.14; H 6.76;
1
N 5.22; S 5.97); H NMR (300 MHz; CDCl3, 296 K): d 8.05
(4H, d, J 7.7, Ar–H), 7.67 (6H, m, Ar–H), 7.03 (4H, d, J 7.5,
Ar–H), 6.95 (4H, s, Ar–H), 6.77 (2H, t, J 7.2, Ar–H), 3.71–3.57
(16H, m, 4 ꢁ O–CH2ꢂ + Ar–CH2–Ar), 1.79 (4H, m, 2 ꢁ
CH2), 1.62 (4H, m, 2 ꢁ CH2), 1.32 (12H, m, 6 ꢁ CH2), 0.96
(6H, t, J 7.1, 2 ꢁ CH3), 0.94 (6H, t, J 7.1, 2 ꢁ CH3); 13C NMR
(75 MHz; CDCl3, 296 K): d 150.7, 139.6, 138.3, 134.1, 133.2,
132.9, 131.2, 129.2, 129.1, 128.9, 128.4, 128.2, 126.5, 77.2, 75.3,
53.7, 31.9, 29.7, 25.6, 23.5, 22.7, 14.1, 10.1; TOF-MS ESI+
required 1072.5 for C60H72N4O10S2, found: 1095.4
[M + Na]+ (100%)
Synthesis of 5,17-bisureido derivatives 7–12. General procedure
5,17-Diaminocalix[4]arene 6 (0.1 g, 0.14 mmol) was stirred in
anhydrous dichloromethane (10 ml) under the atmosphere of
dry nitrogen. The corresponding isocyanate (1.6 mmol) was
added and the reaction mixture was stirred overnight at room
temperature. The reaction was quenched by the addition of
methanol (30 ml) and the precipitate (crude product) was
filtered off. The purification methods are described for each
particular ligand below.
5,17-Bis(N0-benzoylureido)-26,28-dihexyloxy-25,27-dipropoxy-
calix[4]arene (1,3-alternate) 10
The crude product was purified by preparative TLC chromato-
graphy (CHCl3–ethyl acetate 3 : 1) and crystallized from
acetonitrile to give 10 as white crystals in 36% yield, mp.
249–250 1C. Found: C, 74.3; H, 7.2; N, 5.5 (C62H72N4O8
requires C 74.37; H 7.25; N 5.60); 1H NMR (300 MHz;
CDCl3, 296 K): d 10.92 (2H, s, NH), 10.49 (2H, s, NH), 8.05
(4H, d, J 7.2, Ar–H), 7.60–7.42 (6H, m, Ar–H), 7.24 (4H, s,
Ar–H), 7.01 (4H, d, J 7.4, Ar–H), 6.72 (2H, t, J 7.7, Ar–H),
3.67 (4H, d, J 14.6, Ar–CH2–Ar), 3.55 (4H, d, J 14.9,
Ar–CH2–Ar), 3.43 (4H, t, 2 ꢁ O–CH2–), 3.17 (4H, t, 2 ꢁ
O–CH2–), 1.54 (4H, m, 2 ꢁ CH2), 1.31–1.26 (16H, m, 8 ꢁ
CH2), 0.95 (6H, m, 2 ꢁ CH3), 0.64 (6H, m, 2 ꢁ CH3); 13C
NMR (75 MHz; CDCl3, 296 K): d 168.8, 156.7, 153.2, 152.0,
134.3, 133.8, 132.9, 132.5, 131.1, 130.1, 128.6, 128.3, 121.6,
121.1, 71.9, 71.5, 37.6, 32.0, 30.2, 25.6, 22.7, 22.6, 14.2, 9.1;
5,17-Bis(N0-phenylureido)-26,28-dihexyloxy-25,27-dipropoxycalix-
[4]arene (1,3-alternate) 76i
No further purification was needed and the product 7 was
isolated as a white solid in 55% yield, mp 233–235 1C. Found:
C, 76.2; H, 7.7; N, 5.8 (C60H72N4O6 requires C 76.24; H 7.68;
1
N 5.93); H NMR (300 MHz; CDCl3, 296 K): d 7.91 (2H, s,
NH), 7.50 (4H, d, J 7.7, Ar–H), 7.32 (4H, m, Ar–H), 7.05
(2H, t, J 7.7, Ar–H), 7.00–6.97 (8H, m, Ar–H), 6.63 (2H, t, J
7.3, Ar–H), 6.46 (2H, s, NH), 3.68–3.63 (8H, m, O–CH2–),
3.52 (8H, s, Ar–CH2–Ar), 1.80–1.73 (8H, m, 4 ꢁ CH2), 1.57
(8H, m, 4 ꢁ CH2), 1.42 (4H, m, 2 ꢁ CH2), 0.96 (6H, t, J 7.4,
2 ꢁ CH3), 0.87 (6H, t, J 7.3, 2 ꢁ CH3); 13C NMR (75 MHz;
CDCl3, 296 K): d 155.7, 154.5, 153.8, 139.2, 135.2, 133.4,
ꢀc
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New J. Chem., 2009, 33, 612–619 | 617

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TOF-MS ESI+ required 1000.5 for C62H72N4O8, found:
1023.3 [M + Na]+ (100%).
Acknowledgements
This work was supported by the Czech Science Foundation
(Nos. 203/ 06/0738 and 203/07/1424), by the Ministry of
Education, Youth and Sports of the Czech Republic
(OC134), and by the Grant Agency of the Academy of
Sciences of the Czech Republic (No. IAA400720706).
5,17-Bis(N0-chloroacetylureido)-26,28-dihexyloxy-25,27-dipropoxy-
calix[4]arene (1,3-alternate) 11
The precipitated solid was filtered off and washed twice with
methanol to yield pure compound 11 in 69% yield, mp 4300 1C.
Found: C, 65.9; H, 6.9; Cl, 7.4; N, 5.9 (C52H66Cl2N4O8
requires C 66.02; H 7.03; Cl 7.50; N 5.92); 1H NMR (300
MHz; CDCl3, 296 K): d 9.86 (2H, s, NH), 8.73 (2H, s, NH),
7.16 (4H, s, Ar–H), 6.99 (4H, d, J 7.7, Ar–H), 6.69 (2H, t,
J 7.5, Ar–H), 4.19 (4H, s, –CH2Cl), 3.64 (8H, s, Ar–CH2–Ar),
3.56 (4H, t, J 7.9, 2 ꢁ O–CH2–), 3.49 (4H, t, J 6.6, 2 ꢁ
O–CH2–), 1.61 (4H, m, 2 ꢁ CH2), 1.50 (4H, m, 2 ꢁ CH2), 1.30
(12H, m, 6 ꢁ CH2), 0.93 (6H, t, J 6.3, 2 ꢁ CH3), 0.87 (6H, t,
J 6.9, 2 ꢁ CH3); 13C NMR (75 MHz; CDCl3, 296 K): d 168.5,
167.7, 156.8, 154.2, 149.8, 134.5, 133.5, 129.9, 122.4, 121.9,
73.3, 72.0, 42.7, 37.1, 32.1, 30.2, 25.8, 23.5, 22.8, 14.3, 10.4;
TOF-MS ESI+ required 944.4 for C52H66Cl2N4O8, found:
967.4 [M + Na]+ (100%).
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