Novel anion receptors based on thiacalix[4]arene derivatives

Article abstract of DOI:10.1016/j.tet.2004.09.088

Starting from the thiacalix[4]arene tetraacetate, novel derivatives bearing four ureido or thioureido functions on the lower rim have been prepared. As proven by NMR titrations, these compounds can bind anions via hydrogen bonding interactions and represent the first example of anion receptors in the thiacalixarene series. The thiacalix[4]arene-tetraacetates or diacetates (cone) serve as a starting point for novel thiacalixarenes derivatives bearing urea or thiourea units on the lower rim. As revealed by NMR titration experiments, these compounds are preorganised for anion recognition in organic solvents.

Full text of DOI:10.1016/j.tet.2004.09.088

Tetrahedron 60 (2004) 11383–11390
Novel anion receptors based on thiacalix[4]arene derivatives
a
Petra Zlatuskova, Ivan Stibor, Marcela Tkadlecova and Pavel Lhotak
a
b
a,
*
ˇ
´
´
´
a
´
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technicka 5, 166 28 Prague 6, Czech Republic
´
Department of Analytical Chemistry, Prague Institute of Chemical Technology, Technicka 5, 166 28 Prague 6, Czech Republic
b
Received 27 June 2004; revised 2 September 2004; accepted 23 September 2004
Abstract—Starting from the thiacalix[4]arene tetraacetate, novel derivatives bearing four ureido or thioureido functions on the lower rim
have been prepared. As proven by NMR titrations, these compounds can bind anions via hydrogen bonding interactions and represent the first
example of anion receptors in the thiacalixarene series.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
anion recognition. Another interesting group of anion
receptors is represented by compounds capable of ion-pair
recognition (ditopic receptors12), where the calixarene
skeleton holds both cation- and anion-complexing
functions.13
Anion recognition, complexation and transport were
recognised only rather recently as a very important part of
supramolecular chemistry.1 Despite many indispensable
roles in the biochemical processes and pathways, where
anions are frequently engaged in enzymatic reactions as
substrates and/or cofactors, the supramolecular chemistry of
anions is still quite unexplored if compared with that of
cations.
There is much evidence that ureido functions appended to
calixarene can form a suitably pre-organized cavity
(depending on the calixarene conformation used) with
pronounced anion recognition capability. We14 and others15
have reported the cone and the 1,3-alternate calixarenes
bearing urea or thiourea functions on the upper/lower rim
that can bind anions such as halogenides and carboxylates.
There are several different strategies used for anion
complexation so far.2 Basically, the receptors can be
divided into two main groups: (i) charged systems exploring
electrostatic interactions with positively charged species
(polyammonium3 and guanidinium4 salts, quaternary
ammonium salts); (ii) neutral systems5 using other kind of
interactions, such as donor–acceptor interactions (receptors
based on the Lewis acids), hydrogen bonds, hydrophobic
effects etc. Significant progress has been made, especially in
the design and synthesis of neutral receptors based on the
hydrogen bonding interactions. Among them, systems
employing amidic and (thio)urea moieties6 have been
proven especially efficient in the design of anion receptors.
Thiacalixarenes16 have appeared recently as novel members
of the calixarene7 family. The presence of sulfur atoms
instead of CH2 groups induces many novel features17
compared with ‘classical’ calixarenes. Thiacalix[4]arenes
exhibit a broad range of interesting functions such as
different size and conformational behaviour, different
complexation ability, easy oxidation of –S– bridges etc.,
which makes these compounds good candidates for many
applications in supramolecular chemistry.
In this paper we report on the synthesis of thiacalix[4]arene
derivatives bearing ureido or thioureido functions on the
lower rim, which can serve as anion receptors. To the best of
our knowledge, this is the first example of anion recognition
in thiacalixarene series.
Calix[n]arenes are very well-known building blocks7 in
supramolecular chemistry, frequently used as molecular
scaffolds for the synthesis of more elaborated structures.
There are many examples in the literature, where substituted
calixarenes were used for anion complexation.8 Many
different systems exploiting the HB interactions,9 Lewis
acids,10 or charged receptors11 have been introduced for
2. Results and discussion
2.1. Synthesis of receptors
Keywords: Calixarene; Anion receptor; Complexation; NMR titration.
* Corresponding author. Tel.: C420 2 2435 4280; fax: C420 2 2435 4288;
e-mail: lhotakp@vscht.cz
The synthesis started from parent thiacalixarene 1, which
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.088

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P. Zlatuskova et al. / Tetrahedron 60 (2004) 11383–11390
11384
were transformed into the cone tetraacetate 3a (75% yield)
by alkylation with ethyl bromoacetate in refluxing acetone18
using Na2CO3 as a base. Ester 3a was hydrolysed (NaOH,
aqueous ethanol, reflux) to yield the carboxylic acid 3b in
almost quantitative yield (Scheme 1). The carboxylic acid
3b was then reacted with oxalyl chloride to yield the
corresponding acyl chloride19 3c. The crude chloride was
used without purification for subsequent condensation
Scheme 1. (i) BrCH2COOEt/Na2CO3, acetone, reflux (3a, 75%, 4a, 55%, 8a, 51%); (ii) NaOH, EtOH/water, reflux (3b, 99%, 4b, 99%, 8b, 99%); (iii) oxalyl
chloride/CCl4, reflux (3c, 4c, quant.); (iv) ethylenediamine/THF, rt; (v) phenyl isocyanate/i-PrOH, reflux (8% from 3a); (vi) 6a–6c/Et3N/THF, rt (7a, 23%; 7b,
26%; 7c, 22%; 7e, 7%); (vii) i-PrOH, rt (6a, 46%; 6b, 30%; 6c, 17%); (viii) 6a/CDI/DMF, rt (9, 54%).

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11385
(THF/EtN3, rt) with the amino component 6a–6c. The
corresponding tetraamides 7a–7c immobilised in the cone
conformation were obtained after purification by prepara-
tive TLC (silica gel) in 23, 26 and 22% yields, respectively.
showed the two most intense signals corresponding to the
molecular peak [MCNa]C and to the doubly charged
species [MC2Na]2C. Thus, derivative 7e exhibits two
peaks at m/zZ817.64 [MC2Na]2C (65% int.) and 1611.4
[MCNa]C (100% int.), respectively.
The reaction of tetraacetate 3a with an excess of 1,2-
ethanediamine led to an intractable mixture of tetraamine 5,
partly substituted and bridged compounds, that was used
without purification in the next step-reaction with phenyl
isocyanate. This procedure gave the appropriate urea
derivative 7d in 8% yield (overall yield from 3a).
Interestingly, attempts at the direct aminolysis of tetraester
3a with amines 6a–6b were unsuccessful as only very
complicated reaction mixtures were obtained.
1
As the H NMR spectra are almost uninfluenced by the
change of solvent polarity (CDCl3, CDCl3–CD3CNZ4:1,
DMSO-d6) we can conclude that the possible intra-/inter-
molecular hydrogen bonds are very week or absent under
the measuring conditions.
The complexation abilities of receptors 7 and 9 towards ClK
anion were studied by 1H NMR titrations in CDCl3–
CD3CNZ4:1 (v/v) mixture. The addition of Bu4NCl
resulted in the complexation-induced shift of NH
signals (Dz200 Hz). All titration experiments were
performed with constant concentration of receptor (approx.
2!10K4 M) and an increasing concentration of anion
added. These experiments led to well reproducible binding
isotherms corresponding to 1:1 binding (Fig. 1) that were
analysed using an original nonlinear curve-fitting program21
and statistically treated for several various signals. To
confirm the stoichiometry of anion complexation, Job plots
To compare the complexation properties of novel thia-
calix[4]arene derivatives with classical calixarene series,
tetrathioureido receptor 7e was prepared using essentially
the same strategy as described for 7a–7c. Another model
compound, dithioureido receptor 9, was synthesised in order
to evaluate the role of preorganisation and multiplicity of
ureido functions on the lower rim of thiacalixarene. The
synthesis followed the above strategy with one exception-
the amidic bond in 9 was constructed using the reaction of
free0dicarboxylic acid 8b with amine 6a after activation with
N,N -carbonyl diimidazole in 54% yield.
1
were constructed from H NMR titration data. In all cases
studied, the formation of the 1:1 complexes was clearly
substantiated (Fig. 2).
2.2. Structure assignments and the NMR complexation
study
The highest complexation-induced NMR shifts within the
receptor molecules are those of the NH signals. As shown in
Figure 3, both ureido NH protons (Nr. 12 and 14) in 7a are
the most downfield shifted signals after the addition of
5 equiv of chloride. This clearly indicates that the ureido/
thioureido groups create a binding site, which is responsible
for anion binding via synchronous hydrogen bonding
interactions. The comparison with classical calix[4]arene
derivative 7e shows that the binding modes are identical in
both systems.
The structures of novel ureido/thioureido calixarenes were
proven using the combination of 1H NMR spectroscopy and
mass spectroscopy (ESI-MS or FAB MS). The full assign-
ment of 1H and 13C NMR spectra was done using gCOSY,
gHSQC and gHMBC methods. As the synthetic pathway
started from the conformationally immobilised cone tetra-
acetates 3a and 4a of known structures,18a the confor-
mational assignment of products was not necessary. The
conformational preferences of thiacalixarene diacetate 8a
are also known,20 anyhow the structure of derivative 9 was
proved independently by one-dimensional DPFGSE-NOE
experiments. The ESI MS spectra of all receptors usually
As shown in Table 1, the corresponding complexation
constants depend on the length of the lower rim alkylene
chains. The lower is the rigidity of the system (the longer
1
1
Figure 1. H NMR titration curves of 7a with BuC4 NClK (300 MHz, CDCl3–CD3CNZ4:1v/v, 298 K), several various H signals used (see the numbering
scheme).

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11386
Derivatives 7 could, in principle, operate as ditopic
receptors for ion-pair complexation. These molecules
contain a second binding site at the thiacalix[4]arene
lower rim formed by four amidic groups potentially capable
of synchronous binding of alkaline metal cations. The
complexation ability for sodium cations in CDCl3 was
1
determined by H NMR titrations with Kobayashi reagent
NaB[3,5-(CF3)2C6H3]4 (sodium salt well soluble in apolar
solvents). It was found that complexation constants of 7a
(KNaZ1960 MK1) and 7d (KNaZ520 MK1) are very
small if compared with classical calixarene derivative 7e
(KNaO105 MK1).
Figure 2. Job plot for the 7aCBu4NCClK system (1H NMR, 300 MHz,
CDCl3–CD3CNZ4:1v/v).
To test the influence of cation complexation on the anion
1
recognition the H NMR titrations of preformed sodium
complex was carried out. Unfortunately, as the NH signals
are invisible or extensively broadened under the conditions
used, they cannot be used for the construction of titration
curves. The addition of Bu4NCl to the mixture of 7a and
excess of Kobayashi reagent (5 equiv) led to only minor
changes in chemical shifts of aromatic or CH2 signals. As
shown in Figure 4 the titration curves do not correspond to
simple 1:1 binding. Rather than synchronous complexation
of cation and anion they reflect more complex process. As
the separately obtained complexation constants for NaC and
ClK are of the same order (KNaZ1960 MK1 vs KClZ
3480 MK1), it seems highly probable that both processes
(cation vs anion complexations) are competitive rather
than cooperative. The same phenomenon was found for
thiacalixarene 7d (Fig. 5).
Figure 3. Complexation induced 1H NMR chemical shifts in 7a and 7e after
addition of 5 equiv of Bu4NCClK (300 MHz, CDCl3–CD3CNZ4:1 v/v).
In conclusion, easily accessible thiacalix[4]arene tetra-
acetate in the cone conformation was transformed into the
Table 1. Complexation constants K of receptors 7 and 9 towards selected anions (1H NMR, CDCl3–CD3CNZ4:1 v/v, 25 8C, 300 MHz)
Anion
KC [molK1 l]
7a
7b
7c
7d
7e
9
ClK
BrK
IK
3480
830
100
1900
—
—
1790
—
—
4300
990
240
2670
780
250
220
—
—
—
CNK
1740
—
—
2510
5140
—Znot measured.
chain) the weaker is the binding (compare the complexation
constants K for chloride: 7a (3480 MK1), 7b (1900 MK1),
7c (1790 MK1)). The comparison of 7a and 7d shows that
thioureido derivative is slightly worse receptor for chloride
if compared with the corresponding thiacalixarene bearing
ureido functions. On the other hand, both thiacalix[4]arene
receptors 7a and 7d exhibit higher complexation abilities for
chloride than classical calix[4]arene derivative 7e, while the
situation with binding of cyanide anion is just reversed.
The relationship between the number of hydrogen bonds
and the strength of anion complexation can be evaluated by
comparing the binding affinity of 7a (KClZ3480 MK1) with
that of model derivative 9 (KClZ220 MK1) possessing only
two thiourea moieties. The considerable difference (15!) in
the complexation constants clearly demonstrates the
importance of multiple hydrogen bonds and preorganisation
for efficient anion binding.
Figure 4. Complexation induced 1H NMR chemical shifts in 7a/Kobayashi
agent system after addition of Bu4NCl (300 MHz, CDCl3–CD3CNZ4:1
v/v), for numbering see Figure 1.

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11387
3.1.2. Synthesis of 5,11,17,23-tetra-tert-butyl-
25,26,27,28-tetrakis[((N-2-aminoethyl)aminocarbonyl)-
methoxy]thiacalix[4]arene (5). A solution of tetraester 3a
(1.1 g, 1.04 mmol) in 5 ml of absolute THF was added to
40 ml of ethylene diamine (598 mmol) and the mixture was
stirred for four days at rt. The remaining ethylene diamine
was distilled off at a reduced pressure, the residue was
suspended in water, and the precipitate was filtered off. The
crude product (0.92 g) was used without further purification
in the next step. 1H NMR (CDCl3, 300 MHz) d (ppm): 8.33
(broad peak, 4H, NH), 8.10 (b.s., 4H, NH), 7.34 (s, 8H,
H-arom), 4.88 (s, 8H, O–CH2–CO–), 3.43 (m, 8H, –NH–
CH2–CH2–NH2), 2.92 (m, 8H, NH–CH2–CH2–NH2), 1.12
(s, 36H, But).
Figure 5. Competitive cation/anion complexation in derivative 7a.
3.1.3. Synthesis of thioureas. N-(2-Aminoethyl)-N0-phenyl-
thiourea (6a). Phenyl isothiocyanate (2.4 ml, 0.02 mol) in
5 ml of diethyl ether was added dropwise to the solution of
1.2 ml of ethylene-1,2-diamine (0.02 mol) in 30 ml of
isopropyl alcohol over a period of 40 min. The reaction
mixture was then stirred for 2 h at rt and quenched by
addition of 80 ml of diluted HCl (40:1). The solvents were
evaporated, the residue was suspended in hot water and the
resulting precipitate was filtered off. The filtrate was
basified by the addition of solid NaOH, and the product
(1.8 g, 46%) crystallised in the form of white crystals. Mp:
135–136 8C (lit.22 135–137 8C). 1H NMR (CDCl3,
300 MHz) d (ppm): 7.43 (t, 2H, JZ7.7 Hz, H-arom), 7.28
(m, 3H, H-arom), 6.75 (b.s., 2H, NH) 3.67 (m, 2H, NH–
CH2–CH2–NH), 2.92 (t, 2H, JZ5.8 Hz, NH–CH2–CH2–
NH).
corresponding derivatives bearing four ureido or thioureido
functions on the lower rim. The NMR titrations revealed
that these compounds can interact with anions in apolar
solvents via hydrogen bonding interactions and represent
the first example of anion receptors in the thiacalixarene
series.
3. Experimental
3.1. General
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. Dichloromethane and
CCl4 used for the reaction were dried with CaH2 and P2O5,
respectively, and stored over molecular sieves. The purity of
the substances and the course of reactions was monitored by
TLC using TLC aluminium 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).
N-(3-Aminopropyl)-N0-phenylthiourea (6b). Phenyl isothio-
cyanate (2.4 ml, 0.02 mol) in diethyl ether (5 ml) was added
dropwise to the solution of 1.7 ml (0.02 mol) of propan-1,3-
diamine in 30 ml of isopropyl alcohol during 40 min. The
reaction mixture was stirred for 2 h at rt and quenched by
addition of 80 ml of diluted HCl (40:1). The solvents were
evaporated, the residue was suspended in hot water and the
resulting precipitate was filtered off. The filtrate was
basified by NaOH to approx. pHZ10. After standing at rt
the product crystallised to give 1.23 g of white crystals
(30%). Mp: 103–105 8C (lit.23 106–107 8C).1H NMR
(CDCl3, 300 MHz) d (ppm): 7.77 (b.s., 1H, NH), 7.67
(b.s., 1H, NH), 7.38 (t, 2H, JZ7.4 Hz, H-arom), 7.24 (d, 3H,
JZ6.6 Hz, H-arom), 3.74 (m, 2H, NH–CH2–CH2–CH2–
NH2), 2.80 (m, 2H, NH–CH2–CH2–CH2–NH2), 1.66 (m,
2H, NH–CH2–CH2–CH2–NH2), 1.10 (b.s., 2H, NH2).
Starting esters 3a (75%), 4a (77%), and 8a were prepared
according to procedures known20 by the reaction of 1 or 2
with ethyl bromoacetate in boiling acetone in the presence
of Na2CO3 or Cs2CO3.
3.1.1. Preparation of acyl chlorides. Synthesis of
5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis[(chloro-
carbonyl)methoxy]-thiacalix[4]arene (3c). Tetraacid 3b
(0.4 g, 0.42 mmol) was dissolved in anhydrous tetrachloro-
methane (20 ml) and oxalyl chloride (3 ml, 0.034 mol) was
added. The reaction mixture was refluxed for 3 h and the
volatile part of the reaction was distilled off. Fresh
tetrachloromethane (5 ml) was then added and the distilla-
tion was repeated under reduced pressure. The product was
immediately used in the next step.
N-(6-aminohexyl)-N0-phenylthiourea (6c). Phenyl isothio-
cyanate, 2.4 ml (0.02 mol) in diethyl ether (5 ml) was added
dropwise to the solution of 2.32 ml (0.02 mol) hexane-1,6-
diamine in 30 ml of isopropyl alcohol during 40 min. After
addition of all the isothiocyanate, the reaction mixture was
stirred for 2 h at rt and quenched with 80 ml of dilute HCl
(40:1). The solvents were evaporated, the residue was
suspended in hot water and the resulting solid was filtered
off. The filtrate was basified by NaOH to pHZ10 and the
product crystallised from water to give 0.84 g of colourless
Synthesis of 5,11,17,23-tetra-tert-butyl-25,26,27,28-
[(chlorocarbonyl)methoxy]calix[4]arene (4c). Calixarene
4b (0.4 g, 0.45 mmol) was reacted with oxalyl chloride
(3 ml, 0.035 ml) following the same procedure as described
above for 3c. The product was obtained quantitatively, and
was used immediately in the next step.
1
crystals (17%). Mp: 90–92 8C (lit.22 89–92 8C. H NMR
(CDCl3, 300 Hz) d (ppm): 7.73 (b.s., 1H, NH), 7.44 (t, 2H,
JZ7.4 Hz, H-arom), 7.31 (t, 1H, JZ7.7 Hz, H-arom), 7.19
(d, 2H, JZ7.1 Hz, H-arom), 6.03 (b.s., 1H, NH), 3.62 (m,

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P. Zlatuskova et al. / Tetrahedron 60 (2004) 11383–11390
11388
2H, –NH–CH2–CH2–CH2–), 2.66 (m, 2H, –CH2–CH2–
NH2), 1.57 (m, 2H, NH–CH2–CH2–CH2–), 1.42 (m, 2H,
–CH2–CH2–CH2–NH2), 1.32 (m, 4H, –NH–CH2–CH2–
CH2–CH2–CH2–CH2–NH2), 1.02 (b.s., 4H, NH2).
O–CH2–CONH–), 3.59 (m, 8H, NH–CH2–(CH)5–NH), 3.32
(m, 8H, NH–(CH)5–CH2–NH), 1.57 (m, 16H, NH–CH2–
CH2–(CH2)2–CH2–CH2–NH), 1.34 (m, 16H, NH–(CH2)2–
CH2–CH2–(CH2)2–NH), 1.12 (s, 36H, But). IR (CHCl3)
nmax (cmK1): 1665 (CO), 3326 (NH). MS-ESI m/z (rel. int.)
965.67 [MC2Na]2C (98), 1908.2 [MCNa]C (100). EA
calcd for C100H132N12O8S8: C, 63.66; H, 7.05; N, 8.91%.
Found: C, 62.93; H, 7.11; N, 8.71%.24
3.1.4. Synthesis of receptors 7a–7e. Receptor 7a. A
solution of acyl chloride 3c (0.23 g, 0.21 mmol) in 10 ml
of absolute THF was added dropwise to a stirred solution of
N-(2-aminoethyl)-N0-phenylthiourea (0.5 g, 2.56 mmol) in
THF (10 ml) under the nitrogen atmosphere. Triethylamine
(0.4 ml) was then added and the mixture was stirred for
three days at rt. Reaction mixture was quenched by addition
of 1 M aqueous HCl and the product was extracted with
chloroform. The organic layer was dried on MgSO4,
evaporated to dryness and the solid residue was purified
by preparative TLC (petroleum ether–acetoneZ2:1) to give
80 mg of title compound (23%) as a white solid. Mp: 142–
146 8C. 1H NMR (CDCl3–CD3CNZ4:1, 300 MHz) d
(ppm): 8.46 (s, 4H, –NH), 8.30 (b.s., 4H, –NH), 7.35 (s,
8H, H-arom), 7.32 (d, 8H, JZ7.7 Hz, H-arom), 7.30 (t, 8H,
JZ7.8 Hz, H-arom), 7.23 (b.s., 4H, –CH2–CONH–), 7.15 (t,
4H, JZ7.1 Hz, H-arom), 4.87 (s, 8H, O–CH2–CONH–),
3.80 (m, 8H, –NH–CH2–CH2–NH–), 3.54 (m, 8H, –NH–
CH2–CH2–NH–), 1.10 (s, 36H, But). IR (CHCl3) nmax
(cmK1): 1663 (CO), 3306 (NH). MS-ES m/z (rel. int.)
853.10 [MC2Na]2C (33), 1683.27 [MCNa]C (52). EA
calcd for C84H100N12O8S8: C, 60.69; H, 6.06; N, 10.11%.
Found: C, 60.23; H, 6.21; N, 10.01%.24
Receptor 7d. A solution of phenyl isocyanate (0.72 ml,
6.6 mmol) in ether (10 ml) was added to derivative 5
(0.92 g, 0.82 mmol) dissolved in 15 ml of isopropyl alcohol.
The reaction mixture was stirred at rt for 2 h, then 20 ml of
water was added and the product was extracted with
chloroform. The organic layer was dried over MgSO4,
evaporated to dryness and the residue was purified using
column chromatography on silica gel (CHCl3–ethyl
acetateZ100:1) to yield 0.108 g of the product (8% overall
1
from 3a) as a yellowish solid. Mp: 162–166 8C. H NMR
(DMSO-d6, 300 MHz) d (ppm): 8.51 (b.s., 8H, 2NH), 7.37
(s, 8H, H-arom), 7.34 (d, 8H, JZ7.1 Hz, H-arom), 7.18 (t,
8H, JZ7.2 Hz, H-arom), 6.86 (t, 4H, JZ7.0 Hz, H-arom),
6.27 (t, 4H, JZ4.9 Hz, NH), 4.84 (s, 8H, O–CH2–CONH–),
3.29 (m, 8H, NH–CH2–CH2–NH), 3.22 (m, 8H, NH–CH2–
CH2–NH), 1.06 (s, 36H, But). IR (CHCl3) nmax (cmK1):
1659 (CO), 3321 (NH). MS-ESI m/z 1619.3 [MCNa]C. EA
calcd for C84H100N12O12S4: C, 63.13; H, 6.31; N, 10.52%.
Found: C, 62.63; H, 6.02; N, 10.11%.24
Receptor 7e. NK2-aminoethyl-N0-phenylthiourea 6a (0.7 g,
0.0035 mol) and 0.4 ml of triethylamine were dissolved in
anhydrous THF (10 ml) under a nitrogen atmosphere. A
solution of acyl chloride 4c (0.43 g, 0.45 mmol) in 10 ml of
anhydrous THF was added and the mixture was stirred for
three days at rt. The reaction mixture was then quenched by
aqueous 1 M HCl (10 ml) and the product was extracted to
chloroform. The organic layer was dried over MgSO4,
solvent was removed under a reduced pressure, and the
residue was purified by preparative TLC (CHCl3–metha-
nolZ10:1) to yield 50 mg (7%) of product as a white solid.
Receptor 7b. Triethylamine (0.4 ml) was added to the
solution of N-3-aminopropyl-N0-phenylthiourea 6b 0.53 g
(2.5 mmol) in anhydrous THF (10 ml) under nitrogen
atmosphere. Then the solution of acyl chloride 3c (0.23 g,
0.21 mmol) in THF (10 ml) was added and the reaction
mixture was stirred for five days at rt. An aqueous 1 M
solution of HCl was added and the product was extracted
with chloroform. The organic layer was dried over MgSO4,
evaporated to dryness, and the crude product was purified
using the preparative TLC on silica gel (20!20 cm,
chloroform–acetoneZ2:1). The title compound (0.08 g,
1
1
Mp: 136–142 8C. H NMR (CDCl3, 300 MHz) d (ppm):
26%) was obtained as a white solid. Mp: 136–139 8C. H
8.35 (b.s., 4H, NH); 8.20 (b.s., 4H, NH); 7.28–7.19 (m, 24H,
H-arom, NH); 6.77 (s, 8H, H-arom); 4.52 (s, 8H, O–CH2–
CO); 4.43 (d, 4H, JZ13.2 Hz, Ar-CH2-Ar ax.); 3.77 (m, 8H,
–CH2–CH2–); 3.52 (m, 8H, –CH2–CH2–); 3.23 (d, 4H, JZ
13.2 Hz, Ar-CH2-Ar eq.); 1.06 (s, 36H, But). MS-ESI m/z
(rel. int.) 817.64 [MC2Na]2C (65), 1611.4 [MCNa]C
(100). EA calcd for C88H108N12O8S4: C, 66.47; H, 6.85; N,
10.57%. Found: C, 65.98; H, 6.88; N, 10.17%.24
NMR (CDCl3, 300 MHz) d (ppm): 8.23 (b.s., 4H, NH), 7.97
(b.s., 4H, NH), 7.35 (m, 8H, H-arom), 7.33 (s, 8H, H-arom),
7.25 (m, 8H, H-arom), 7.20 (m, 4H, H-arom), 6.99 (b.s., 4H,
NH), 4.79 (s, 8H, O–CH2–CONH–), 3.62 (m, 8H, NH–
CH2–CH2–CH2–NH), 3.31 (m, 8H, NH–CH2–CH2–CH2–
NH), 1.81 (m, 8H, NH–CH2–CH2–CH2–NH2), 1.11 (s, 36H,
But). IR (CHCl3) nmax (cmK1): 1663 (C]O), 3317 (NH).
MS-ESI m/z (rel int.) 881.63 [MC2Na]2C (66), 1740.28
[MCNa]C (100). EA calcd for C88H108N12O8S8: C, 61.51;
H, 6.33; N, 9.78%. Found: C, 61.13; H, 6.56; N, 9.84%.24
3.1.5. Synthesis of receptor 9. Di-acid 8b (0.117 g,
0.14 mmol) was dissolved in 20 ml of dry DMF under the
nitrogen atmosphere, the N,N0-carbonyl diimidazole
(0.05 g, 0.294 mmol) was added and the mixture was stirred
for 1 h at rt. A solution of N-(2-aminoethyl)-N0-phenyl-
thiourea 6a (0.11 g, 0.56 mmol) in DMF was added and the
mixture was heated to 70 8C overnight. The solvents were
distilled off under a reduced pressure and the remaining
solid was purified by the preparative TLC on silica gel
(CHCl3–acetoneZ10:1) to give 90 mg of product (54%) as
a white solid. Mp: 181–183 8C. 1H NMR (CDCl3–
CD3CNZ4:1) d (ppm): 8.45 (s, 2H, OH), 8.27 (b.s., 2H,
NH), 8.12 (b.s., 2H, NH), 7.53 (s, 4H, H-arom), 7.16 (s, 4H,
Receptor 7c. N-6-Aminohexyl-N0-phenylthiourea 6c
(0.44 g, 1.753 mmol) was dissolved in anhydrous THF
(10 ml) under nitrogen atmosphere and treated with
triethylamine (0.3 ml) and the solution of 3c (0.16 g,
0.14 mmol) in THF (5 ml) was added. The reaction mixture
was then stirred for five days at rt and purified as described
above for 7b to give 0.062 g of product (22%) as a white
solid. Mp: 96–99 8C. 1H NMR (CDCl3, 300 MHz) d (ppm):
8.06 (s, 4H, SH), 7.98 (b.s., 4H, NH), 7.36 (s, 8H, Ar-H),
7.36 (m, 8H, H-arom), 7.29 (m, 8H, H-arom), 7.19 (t, 4H,
JZ7.2 Hz, H-arom), 6.58 (b.s., 4H, NH), 4.79 (s, 8H,

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P. Zlatuskova et al. / Tetrahedron 60 (2004) 11383–11390
11389
8. Matthews, S. E.; Beer, P. D. Calixarenes 2001 2001. Ref. 7(a),
pp 421–439.
H-arom), 7.12 (m, 8H, H-arom), 6.98 (m, 2H, H-arom), 6.91
(b.s., 2H, NH), 4.77 (s, 4H, O–CH2–CONH–), 3.76 (m, 4H,
NH–CH2–CH2–NH), 3.56 (m, 4H, NH–CH2–CH2–NH),
1.17 (s, 18H, But), 0.83 (s, 18H, But). IR (CHCl3) nmax
(cmK1): 1671 (CO), 3340 (NH). MS ES m/z (rel. int.)
1191.09 [MCH]C (22), 1213.1 [MCNa]C (100). EA calcd
for C62H74N6O6S6: C, 62.49; H, 6.26; N, 7.05%. Found: C,
61.88; H, 6.31; N, 6.87%.
9. See e.g.: (a) Morzherin, Y.; Rudkevich, D. M.; Verboom, W.;
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We thank the Grant Agency of the Czech Republic (No.
203/03/0926) and the Ministry of Education, Youth and
Sport of the Czech Republic (MSM:223400008) for
financial support.
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