P-tert-Butyl thiacalix[4]arenes functionalized at the lower rim by amide, hydroxyl and ester groups as anion receptors

Article abstract of DOI:10.1039/c0ob01251c

New p-tert-butyl thiacalix[4]arenes differently substituted at the lower rim with amide, hydroxyl and ester groups were synthesized. Binding properties of the compounds toward some tetrabutylammonium salts n-Bu₄NX (X = F^-, Cl^-, Br^-, I^-, CH ₃CO₂^-, H₂PO₄^-, NO₃^-) were studied by UV spectroscopy. It was found that the stoichiometry of the complexes, generally, is 1:1, and the association constants are in the range of 10³-10⁵ M^-1. The p-tert-butyl thiacalix[4]arenes containing secondary amide groups trisubstituted at the lower rim bind the studied anions most effectively. Selective receptors for fluoride and dihydrogen phosphate salts of tetrabutylammonium were found.

Full text of DOI:10.1039/c0ob01251c

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PAPER
p-tert-Butyl thiacalix[4]arenes functionalized at the lower rim by amide,
hydroxyl and ester groups as anion receptors†
Ivan I. Stoikov,*a Alena A. Yantemirova,a Roman V. Nosov,a Ildar Kh. Rizvanov,b Ajdar R. Julmetov,a
Vladimir V. Klochkov,a Igor S. Antipin,a Alexander I. Konovalova and Ilya Zharovc
Received 24th December 2010, Accepted 17th February 2011
DOI: 10.1039/c0ob01251c
New p-tert-butyl thiacalix[4]arenes differently substituted at the lower rim with amide, hydroxyl and
ester groups were synthesized. Binding properties of the compounds toward some tetrabutylammonium
salts n-Bu4NX (X = F-, Cl-, Br-, I-, CH3CO2 , H2PO4 , NO3 ) were studied by UV spectroscopy. It was
found that the stoichiometry of the complexes, generally, is 1 : 1, and the association constants are in the
range of 103–105 M-1. The p-tert-butyl thiacalix[4]arenes containing secondary amide groups
trisubstituted at the lower rim bind the studied anions most effectively. Selective receptors for fluoride
and dihydrogen phosphate salts of tetrabutylammonium were found.
-
-
-
Previously, successful selective 1,3-dialkylation of the lower
Introduction
rim of p-tert-butyl thiacalix[4]arene with N-(p-nitrophenyl)-a-
bromoacetamide (NPNBA)18 was performed in the framework
of the elaboration of new approaches to the synthesis of synthetic
receptors with different substituents. In this respect, it was interest-
ing to investigate the conditions for the further functionalization
of the macrocycle 2 (see Scheme 1 below) by ester and amide
fragments. Also, the complexation properties of 1,2-di-, 1,3-di-, tri-
and tetrasubstituted p-tert-butyl thiacalix[4]arenes bearing N-(p-
nitrophenyl)acetamide fragments toward anions were compared.
The potential uses of products of supramolecular chemistry
and the ability of these products to exhibit properties typical
of highly organized biomolecules, e.g. molecular recognition,
catalysis, active and selective transport, has promoted research
in the chemistry of synthetic receptors.1 Calixarenes2–7 and
thiacalixarenes8–10 are widely used as building blocks in the design
of host molecules11,12 because of their unique three-dimensional
structure and the simplicity of functionalization of the macrocyclic
platform.13 The design and synthesis of systems capable of recog-
nizing anions, continues to be one of the challenging problems in
supramolecular chemistry.14–16 It is well known that proton donor
groups, such as amide, hydroxyl or thioureido11 groups are used for
anion binding. The variety in conformations of thiacalix[4]arene
isomers (cone, partial cone, 1,2-alternate, 1,3-alternate) and the
possibility of variation in the number and nature of substituents
allow reaching optimal spatial orientation of binding sites adjusted
for specific types of substrates.
Scheme 1 (i) NPNBA/Na2CO3, CH3CN, reflux;18 (ii) NPNBA/Cs2CO3,
Regioselective functionalization of the lower rim of the thia-
analog of calixarene is significantly complicated because of the
difficulties in selection of the reaction conditions (ratio of reagents,
temperature and duration of the synthesis).10,17 Therefore, synthe-
sis of thiacalix[4]arenes with different substituents at the lower
rim is commonly more difficult than that of the other similar
macrocycles substituted with identical fragments.10,17
CH3CN, reflux.18
Results and discussion
Synthesis of the p-tert-butyl thiacalix[4]arene derivatives
containing N-(p-nitrophenyl)-acetamide and ester fragments at the
lower rim
aA.M. Butlerov Chemical Institute, Kazan (Volga Region) Federal Uni-
versity, 420008 Kremlevskaya, 18, Kazan, Russian Federation. E-mail:
Ivan.Stoikov@mail.ru; Fax: +7 843 275 2253; Tel: +7 843 233 7462
Previously it was shown, that NPNBA can be used as a re-
gioselective alkylation reagent for p-tert-butyl thiacalix[4]arene.
Depending on the nature of alkali metal carbonate and solvent,
thiacalix[4]arenes partially substituted at the lower rim, i.e. 1,2-
di-, 1,3-di- and trisubstituted p-tert-butyl thiacalix[4]arenes in the
partial cone conformation, can be obtained (Scheme 1).18
bRussian Academy of Sciences, A.E. Arbuzov Institute of Organic and
Physical Chemistry, Kazan, Russian Federation
cUniversity of Utah, Salt Lake City, Utah, 84112, United States of America
† Electronic supplementary information (ESI) available: 1H, 13C NMR
and MS spectra of all new compounds have been provided. See DOI:
10.1039/c0ob01251c
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Table 1 Product yields of alkylation of compound 2 by ethyl bromoac-
etate corrected by the amount of initial thiacalix[4]arene 2 isolated from
the reaction media, (R = -CH2C(O)OEt)
To obtain thiacalix[4]arenes differently substituted at the lower
rim, the influence of the conditions of macrocycle 2 alkylation
(temperature, time, solvent, a ratio of reagents, the nature of the
base) on its stereo- and regiospecificity was studied. Interaction
of p-tert-butyl thiacalix[4]arene 2 with ethyl bromoacetate in the
presence of alkali metal carbonates (sodium, potassium, caesium)
in acetone was investigated (Scheme 2). The base and solvent were
specified in accordance with their efficiency in alkylation of p-tert-
butyl thiacalix[4]arene at the lower rim.19
Base
2 : RBr : M2CO3 Time, h Yield (%)
5
6
7
8
Na2CO3 1 : 4 : 3
K2CO3 1 : 4 : 3
Cs2CO3 1 : 4 : 3
Na2CO3 1 : 8 : 8
50
60
20
60
60
20
60
58
50
6
74
30
50
33
58
10 40
—
39 35
5
—
2
—
—
—
3
—
—
—
—
—
—
—
—
50
—
3
K2CO3
Cs2CO3 1 : 8 : 8
K2CO3 1 : 40 : 3
1 : 8 : 8
25
—
17 14
Scheme 3 (i) NPNBA/Na2CO3, acetone, reflux; (ii) BrCH2COOEt/
K2CO3, acetone, reflux; (iii) BrCH2COOEt/Cs2CO3, acetone, reflux.
Alkylation of 2-(4-tert-butylphenoxy)-N-(4¢-nitrophen-1¢-
yl)acetamide 10 by ethyl bromoacetate was performed in similar
conditions to the synthesis of thiacalix[4]arenes 7 and 8 in the
presence of alkali metal carbonates (sodium, potassium, caesium)
in acetone. In the case of sodium carbonate, the reaction did not
run and the initial compound 10 was quantitatively isolated. But,
compounds 11 (59%) and 12 (32%) were obtained with potassium
and caesium carbonates, respectively (Scheme 3).
A simple possible mechanism for the formation of compound
8 of hydrolysis of the amide fragment and formation of a diacid,
was tested in the alkylation of diacid by ethyl bromoacetate. This
reaction did not lead to the formation of the expected compound
8. Therefore Scheme 4 was suggested based on the results obtained
from Schemes 2 and 3. The first stage involves the formation of
enol from compound 10 which is followed by deprotonation of
the OH group promoted by the base with subsequent nucleophilic
substitution with ethyl bromoacetate. The use of caesium carbon-
ate as a base, leads to subsequent deprotonation of compound 11
followed by nucleophilic substitution of ethyl bromoacetate with
the formation of compound 12.
Scheme
2 (i) BrCH2COOEt/Na2CO3, acetone, reflux; (ii)
BrCH2COOEt/K2CO3, acetone, reflux; (iii) BrCH2COOEt/Cs2CO3,
acetone, reflux; (iv) NH2CH2CH2OH, THF, reflux.
It was found that tri- and tetrasubstituted p-tert-butyl
thiacalix[4]arenes 5–8 are formed depending on the ratio of
reagents (Table 1). In the case of sodium carbonate, a trisubstituted
lower rim product p-tert-butyl thiacalix[4]arene 5 in the cone con-
formation was isolated as a major product (58% yield). However,
a tetrasubstituted lower rim product p-tert-butyl thiacalix[4]arene
6 in the cone configuration was obtained in the presence of
potassium carbonate in 40% yield. As predicted, an increase in
the ratio of alkylating reagent and use of potassium carbonate
resulted in N-alkylation of the amide fragment and formation of a
tetrasubstituted lower rim product p-tert-butyl thiacalix[4]arene 7
(14% yield). However, in the case of caesium carbonate, compound
8 without the amide group was obtained in 50% yield. It is
worth noting that the macrocycles 5–7 formed in the presence of
potassium and sodium carbonates are in the cone conformation.
To establish the mechanism of the formation of compounds
7 and 8, model alkylation reactions of 2-(4-tert-butylphenoxy)-
N-(4¢-nitrophen-1¢-yl)acetamide with ethyl bromoacetate were
carried out (Scheme 3). At first, 2-(4-tert-butylphenoxy)-N-(4¢-
nitrophen-1¢-yl)acetamide 10 was synthesized in acetone by the
interaction of p-tert-butylphenol 9 with N-(p-nitrophenyl)-a-
bromoacetamide in 73% yield (Scheme 3).
Scheme 4 Supposed scheme of formation of compound 11.
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Table 2 Product yields of alkylation of compound
diethylbromoacetamide, (R = -CH2C(O)NEt2)
2 by N,N-
Then the chemical properties of the ester groups in
thiacalix[4]arenes 5 and 6 were studied using, as an example, their
interaction with 2-aminoethanol in THF (Scheme 2). Trisubsti-
tuted p-tert-butyl thiacalix[4]arene derivative 13 was obtained in
98% yield. The yield of tetrasubstituted analog 14 is significantly
lower (48%) probably due to steric hindrance at the reaction centre
and possible formation of minor products.
For the synthesis of stereoisomers of thiacalix[4]arene 6 (cone,
partial cone, 1,3-alternate), alkylation of the di-ether based on
p-tert-butyl thiacalix[4]arene 1520 by NPNBA in the presence
of different alkali metal carbonates in acetone was studied. As
predicted, in the presence of alkali metal carbonates M2CO3 (M =
Na, K, Cs) the template effect of cations is observed. In the case of
sodium carbonate, cone stereoisomer 6 was isolated in 60% yield;
in the case of potassium carbonate partial cone stereoisomer 16 and
1,3-alternate stereoisomer 17 were isolated in 30% and 49% yields,
respectively; and in the case of caesium carbonate 1,3-alternate
stereoisomer 17 was isolated in 50% yield (Scheme 5).
Base
2 : RBr : M2CO3
Time, h
Yield (%) 18
19
20
Na2CO3
Na2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
1 : 4 : 3
1 : 8 : 8
1 : 4 : 3
1 : 8 : 8
1 : 4 : 3
1 : 8 : 8
30
12
20
10
10
10
93
62
81
45
40
40
78
62
81
45
—
40
—
—
—
—
40
—
15
11
—
—
—
—
For the purpose of variation in the proton acceptor ability
of the carbonyl group in thiacalix[4]arenes, i.e. ester groups in
compounds 5, 6, 16, 17, tri- and tetrasubstituted derivatives
18–20 containing N,N-diethylacetamide group have been syn-
thesized (Scheme 6). Interaction of 1,3-disubstituted p-tert-butyl
thiacalix[4]arene 2 with N,N-diethylbromoacetamide with various
alkali metal carbonates in acetone has been studied (Table 2).
It appeared that an increase in the ratio of the alkylation
reagent doesn’t lead to formation of tetrasubstituted products.
As a rule, trisubstituted thiacalix[4]arene 18 in the cone confor-
mation is formed. However, at the ratio of reagents 1 : 4 : 3 =
2 : RBr : M2CO3 and using caesium carbonate as the base, trisub-
stituted thiacalix[4]arene 19 in the partial cone conformation is
formed. Tetrasubstituted product 20 is formed when the synthesis
time was increased to 30 h and sodium carbonate was used as a
base.
The structure and the composition of new thiacalix[4]arene
derivatives 5–8, 13, 14 and 16–20 were confirmed by 1H, 13C, 2D
NOESY NMR and IR spectroscopies, mass spectrometry (EI,
ESI, MALDI-TOF) and elemental analysis. Conformations of
synthesized macrocycles were established by 2D NOESY NMR
spectroscopy.
Scheme
5
(i) BrCH2C(O)OEt/Na2CO3, acetone, reflux;20 (ii)
The occurrence of two singlets of tert-butyl protons, two singlets
of oxymethylene protons, two singlets of aromatic protons in the
1H NMR spectra of thiacalix[4]arenes differently substituted at the
lower rim (6, 14, 17, 20) indicates their symmetric structure. How-
ever, in the 1H NMR spectra of trisubstituted thiacalix[4]arenes 5,
13, 18, 19, signals of oxymethylene protons are observed as one
singlet and as an AB system due to diastereotopy of -O–CH2-
protons of the N-p-nitrophenylamide substituent. Also, the signal
NPNBA/Na2CO3, acetone, reflux; (iii) NPNBA/K2CO3, acetone,
reflux; (iv) NPNBA/Cs2CO3, acetone, reflux.
1
of hydroxyl proton at 7.5–9.5 ppm in the H NMR spectra of
compounds 5, 18, 19 testifies to the incomplete alkylation of the
parent thiacalix[4]arene.
The IR spectra of the obtained compounds 5, 6, 7, 8, 16,
17 show an ester band (nmax 1750–1790 cm-1), which is absent
in the IR spectrum of the parent thiacalix[4]arene 2. In the
IR spectra of trisubstituted thiacalix[4]arenes 5, 18, 19, the
absorption band of valence vibrations of the hydroxyl group
(nmax 3456, 3274, 3301 cm-1, respectively) is observed which is
absent in the IR spectra of tetrasubstituted thiacalix[4]arenes
6 and 20. Amide, nitro and -C(O)–N- group bands are absent
in the IR spectrum of the tetrasubstituted lower rim product
thiacalix[4]arene 8. Also in the IR spectra of stereoisomers of
tetrasubstituted thiacalix[4]arenes cone, partial cone, 1,3-alternate
6, 16, 17, respectively, the absorption band of valence vibrations
of the hydroxyl group is absent, which testifies to the complete
substitution of initial di-ether 15.
Scheme
6
(i) BrCH2C(O)NEt2/K2CO3, acetone, reflux; (ii)
BrCH2C(O)NEt2/Cs2CO3, acetone, reflux; (iii) BrCH2C(O)NEt2/
Na2CO3, acetone, reflux.
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Anion complexation study of the synthesized thiacalix[4]arenes by
UV-spectroscopy
a result, the interaction between thiacalix[4]arene 20 and anions is
not observed.
Complexation properties of thiacalix[4]arenes 2, 3, 4, 5, 13, 18,
and 19 were also studied by NMR spectroscopy. In the 1H NMR
spectra of the compounds recorded in the presence of anions, a
hydroxyl proton signal was observed. Thus, no deprotonation of
phenolic hydroxyl took place. For an estimation of the possibility
of tetrabutylammonium cations binding with the synthesized
thiacalix[4]arenes, solutions of compounds 2–6, 13, 14, 16–20 in
the presence of a 10-fold excess of n-Bu4NX (X = F-, Cl-, Br-, I-,
For the design of anionic substrate receptors,11 positively charged
groups, e.g. HN+, able to form hydrogen bonds N+H . . . X- and
electrostatically interact with anions21 and also neutral polar
fragments, such as amide,22 urea,23,24 thiaurea,25 central ions of
metals in metallocenes,26 are commonly used. Thiacalix[4]arenes
substituted on both the upper and lower rims10,11,17,27–29 and
functionalized by corresponding groups also show good potential
as synthetic anion receptors.10
CH3CO2 , H2PO4 , NO3 ) in CDCl3 have been studied by 1H NMR
spectroscopy. In 1H NMR spectra, chemical shifts of the protons
in n-Bu4N+ do not change indicating the absence of interaction
between the thiacalix[4]arenes with tetrabutylammonium cation.
Maximal changes were observed in the case of the interaction of
macrocycle 2 with n-Bu4NF. Bathochromic shift of the absorption
maximum at 306 nm by 8 nm and hyperchromic effect in the
fields of 330–380 nm and 270–290 nm occurred in this case. In
the case of compound 5, containing one ester fragment, another
characteristic in the changes in absorption spectra was observed.
Interaction of thiacalix[4]arene 5 with tetrabutylammonium salts
did not induce the shift of the absorption maximum. A hyper-
chromic effect on absorption bands in the fields of 270–300 nm
and 320–380 nm was observed.
-
-
-
There are some examples of the synthesis of thiacalix[4]arenes
containing secondary amide fragments which can form complexes
with anions.11,27–29 To study the influence of structural factors (the
conformation of the macrocycle, the number and the nature of
the substituents) on the complexation properties of the lower rim
substituted p-tert-butyl thiacalix[4]arenes, the receptor properties
of the compounds 2–6, 10, 13, 14, 16–20 toward the tetrabutylam-
monium salts n-Bu4NX (X = F-, Cl-, Br-, I-, CH3CO2 , H2PO4 ,
-
-
-
NO3 ) were investigated by UV spectroscopy. In these compounds,
both proton donating secondary amide (p-nitrophenylacetamide
and monoethanolamide fragments) and hydroxyl (alcoholic and
phenolic) groups can participate in anion binding.
The influence of the complexation ability of compounds 2–6, 10,
13, 14, 16–20 with anions on absorption spectra have been studied
in the presence of a 200-fold excess of tetrabutylammonium salts
in chloroform. The most significant changes in absorption spectra
obtained with p-tert-butyl thiacalix[4]arenes in the presence of
tetrabutylammonium salts, were observed for the interaction of
the studied macrocycles with acetate, dihydrogen phosphate and
fluoride tetrabutylammonium, and in the case of macrocycle 19
even when chloride, bromide, nitrate tetrabutylammonium were
added. In these spectra, bathochromic shift of the absorption
band in the field of 300–340 nm took place. In the case of
p-tert-butyl thiacalix[4]arenes 16, 17 and 20 in the presence
of studied tetrabutylammonium salts changes in absorption
spectra were not observed which testifies to the absence of
interactions between these compounds and tetrabutylammonium
salts.
The character of the changes in the absorption spectra is
identical for complexes of macrocycle 3 with n-Bu4NX (X =
F-, CH3CO2 , H2PO4 ). A bathochromic shift and hypochromic
effect of the absorption maximum at 306 nm occurred. Also a
hyperchromic effect on the absorption band at 310–380 nm was
observed.
-
-
The character of the changes in the absorption spectra is
complicated for the interaction of compound 4 with n-Bu4NX.
A bathochromic shift and hypochromic effect of the absorption
maximum at 306 nm were observed. Also, a new absorption
maximum at 325 nm appeared. The fluoride ion caused the
strongest changes in the absorption spectrum.
In the case of thiacalix[4]arene 6 containing two ester fragments
(which are proton acceptor binding sites) changes in the absorp-
tion spectra were observed only in the presence of dihydrogen
phosphate ion.
Maximal changes in the absorption spectra of macrocycle 13
were observed in the presence of n-Bu4NF (Fig. 1). In this case,
a bathochromic shift at 300 nm by 40 nm, a hyperchromic effect
at 350–390 nm and a hypochromic effect at 270–330 nm on the
absorption maximum were found.
The most significant changes in the absorption spectra were
observed only for the interaction of macrocycle 18 with n-Bu4NF.
In this case a bathochromic shift by 10 nm of the absorption
maximum at 310 nm and a hypochromic effect on the absorption
band at 310–340 nm were found.
Compounds 16 and 17 are in partial cone and 1,3-alternate
configuration, respectively, and apparently, the bulky tert-butyl
groups hinder the complexation with anions.30,31 It results in
sterical hindrance and complexation with anions in the case of
thiacalix[4]arenes 16 and 17 is not observed.
The macrocycle 20 contains tertiary amide groups. It is known
that the carbonyl group in tertiary amide groups is a stronger
electron donor than the carbonyl group of an ester fragment. For
quantitative estimation of the donor ability of the investigated
ester and N,N-diethylacetamide groups, the donor number values
(DN)32 of ethyl acetate and N,N-diethylacetamide were used as
model compounds. The DN values of ethyl acetate and N,N-
diethylacetamide are equal to 17.1 and 32.2, respectively. These
data indicate that the N,N-diethylacetamide group interacts more
strongly than the ethoxycarbonyl group with Lewis acids. There-
fore the carbonyl group of the N,N-diethylacetamide fragment
in macrocycle 20 interacts more strongly with the amide proton
of N-(p-nitrophenyl)acetamide fragment in comparison with
thiacalix[4]arene 6. Undoubtedly, this affects the intramolecular
hydrogen bond between the carbonyl group and amide proton. As
The character of the changes in the absorption spectra are iden-
tical for complexes of thiacalix[4]arene 19 with n-Bu4NX (X = F-,
Cl-, Br-, CH3CO2 , H2PO4 , NO3 ). In this case, a bathochromic
shift and hypochromic effect of absorption maximum at 303 nm
and also a hyperchromic effect on the absorption band at 330–
400 nm were observed.
-
-
-
The association constants and the stoichiometry (Table 3) of the
formed complexes were obtained for quantitative evaluation of the
complexation ability of compounds 2–6, 10, 13, 14, 18, 19 towards
3228 | Org. Biomol. Chem., 2011, 9, 3225–3234
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Fig. 1 Changes in the absorption spectra of compound 13 after adding
salts n-Bu4NX (X = F-, CH3CO2-, H2PO4-, CHCl3, C13 = 2.5 ¥ 10-5 M,
Cn-Bu4NX = 5.0 ¥ 10-3 M).
Fig. 3 UV absorption spectra obtained by titration of the complexed
system containing the receptor 14 (C14 = 2.5 ¥ 10-5 M) and dihydrogen
phosphate ion (Cinitial = 2.5 ¥ 10-5 M, Cfinal = 5.0 ¥ 10-3 M) in CHCl3. Inset:
titration curve (C14 = 2.5 ¥ 10-5 M).
some anions (F-, CH3CO2 , H2PO4 ). It was found by using the
isomolar series method, that all the studied thiacalix[4]arenes form
in CHCl3 1 : 1 complexes with considered tetrabutylammonium
salts (Fig. 2). However, 1,2-disubstituted thiacalix[4]arene 4 forms
1 : 2 complexes. The stoichiometry of the complexation was also
confirmed by measuring Job’s plots (Fig. 2). The association
constants of the studied complexes were estimated in chloroform
by the dilution method (Fig. 3). The appropriate complexation
constants (Table 3) were calculated using the Benesi–Hildebrand
method.33
-
-
To estimate the contribution of the thiacalix[4]arene platform
in anion binding, receptor properties of the model compound 10
were investigated. It was found that the association constants of
compound 10 with anions were at least one order of magnitude
lower compared with the association constants of all investigated
macrocycles with anions (Table 3). In this case a macrocyclic
cooperative effect is observed: the groups which have either weak,
or no complexation ability form complementary binding sites in
the thiacalix[4]arene due to the spatial preorganization.
Introduction of an ester fragment into the lower rim
of 1,3-disubstituted thiacalix[4]arene
2
containing N-(p-
nitrophenyl)acetamide groups leads to an increase in preorga-
nization of the molecule and changes in the intramolecular
hydrogen bonds between amide protons and the carbonyl group.
It results in higher complementarity of the macrocycle towards
the anions tested. This was proved by an increase of the as-
sociation constant by one order of magnitude observed for the
complexes of 5 with anions in comparison with those of the
parent thiacalix[4]arene 2 (Table 3). Probably, the introduction
of a second ester fragment (compound 6) leads to formation of
a pseudo-cavity for the dihydrogen phosphate ion. It should be
noted that in the case of tetrasubstituted thiacalix[4]arene 6 the
logarithm of the association constant with dihydrogen phosphate
Fig. 2 Job’s plot for the 14 + n-Bu4NH2PO4 system.
Table 3 The logarithms of the association constant (logKass) for complexation of compounds 2–6, 10, 13, 14, 18, 19 with n-Bu4NX (X = F-, Cl-, Br-,
H2PO4-, CH3CO2-, NO3-) in CHCl3 (at 25 ◦C)
logKass
-
-
-
Compound
Host : Guest
F-
Cl-
Br-
H2PO4
CH3CO2
NO3
a
a
a
2
1 : 1
1 : 1
1 : 2
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
3.67 0.19
5.25 0.56
7.38 0.17
4.27 0.24
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
3.41 0.09
4.93 0.21
7.52 0.19
4.43 0.34
2.98 0.23
2.81 0.27
3.51 0.02
3.24 0.28
3.50 0.32
4.85 0.12
7.58 0.26
4.48 0.22
—
—
—
—
—
—
—
—
a
a
a
3
a
a
a
4
a
a
a
5
a
a
a
a
a
6
—
—
a
a
a
10
13
14
18
19
2.52 0.48
4.55 0.18
3.68 0.22
3.53 0.44
3.80 0.32
2.32 0.56
3.48 0.10
3.15 0.05
a
a
a
a
a
a
a
a
a
a
a
—
—
—
—
—
3.36 0.18
2.93 0.04
3.51 0.10
3.37 0.11
2.64 0.09
a No changes in UV spectra.
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ion is similar to model compound 10. It is obvious that the
decrease in the efficiency of anion binding due to the formation
of hydrogen bonds NH . . . O C leads to the selective binding of
tetrabutylammonium dihydrogen phosphate.
In the case of macrocycles 13 and 14, the number of proton
donating groups increases from the trisubstituted (13) to the
tetrasubstituted (14) compound. Therefore, the increase of the
association constant for the studied anions can be expected after
introduction of the second monoethanolamide fragment to the
lower rim of thiacalix[4]arene.
The association constants of anion binding appear to be similar
for compounds 13 and 14 except those for the fluoride ion. It
should be noted that the association constant of fluoride binding
was higher by one order of magnitude for macrocycle 13 than for
thiacalix[4]arene 14. Probably, the unsubstituted phenolic group
at the lower rim of thiacalix[4]arene 13 interacts more effectively
with the fluoride ion.
Trisubstituted thiacalix[4]arene 18 in the cone conformation
with high selectivity binds fluoride ion in comparison with other
studied anions. Probably, the presence of the bulky diethylamide
group complicates the binding of other anions. However, trisubsti-
tuted thiacalix[4]arene 19 in the partial cone conformation effec-
tively binds almost all studied anions except the bulky iodide ion.
In the series of trisubstituted thiacalix[4]arenes 3, 5, 13, 18
and 19, macrocycle 3 in the partial cone conformation binds
anions more effectively (Table 3). In general, trisubstituted
thiacalix[4]arenes bind anions more effectively than tetrasubsti-
tuted thiacalix[4]arenes. This might be due to the free phenolic
hydroxyl that could participate in anion binding.
received without additional purification. Organic solvents were
purified by standard procedures. 1H NMR spectra were recorded
at room temperature with a 300 MHz Varian XL-300 spectrometer
in CDCl3 as a solvent; chemical shifts are reported in ppm.
The 2D and 13C NMR spectra were recorded on a Bruker-
500 MHz instrument in CDCl3 at room temperature. IR spectra
(nujol) were recorded with a Vector 22 (Bruker) IR spectrometer.
Mass spectra were recorded with a Bruker Esquire MS, MALDI-
TOF Dynamo Finnigan (with 1,8,9-trihydroxyanthracene or 4-
nitroaniline matrices), Varian MAT 312. Elemental analysis was
performed with a Perkin–Elmer 2400 Series II instruments.
General procedure for the preparation of thiacalix[4]arenes 5–8
5,11,17,23-Tetra-tert-butyl-25,27-bis-hydroxy-26,28-bis[N-(4¢-
nitrophenyl)-aminocarbonylmethoxy]-thiacalix[4]arene 2 (1 g,
1.39 mmol) was suspended in 30 mL of dry acetone containing a
3-fold (or a 8-fold) excess of an anhydrous alkali metal carbonates.
Then a 4-, 8- or 40-fold excess of ethyl bromoacetate and 40 mL
of dry acetone was added. The mixture was refluxed for several
hours. The reaction was monitored by TLC. After cooling, the
solid residue was removed by filtration. The filtrate was evaporated
to dryness. Then, both solids were treated separately using the
same procedure. Solid was dissolved in 30 ml of chloroform and
washed with 30 mL of 2 M HCl. The organic layer was dried over
molecular sieves, filtered and evaporated under reduced pressure.
Crystallization of the resulting solid from chloroform–ethanol or
dichloromethane–ethanol mixture gave pure samples of 5–8. In
the case of compound 8, the compounds 11 and 12 were also
isolated.
5,11,17,23-Tetra-tert-butyl-25-hydroxy-27-[(ethoxycarbonyl)-
methoxy]-26,28-bis[N -(4¢-nitrophenyl)-aminocarbonylmethoxy]-
thiacalix[4]arene (5). Yield 0.41 g (58%). Mp: 275 ◦C. 1H NMR
(300 MHz, CDCl3) d (ppm): 0.84 (s, 9H, (CH3)3C), 1.13 (s, 9H,
(CH3)3C), 1.22 (s, 18H, (CH3)3C), 1.31 (t, 3H, -O–CH2–CH3,
Conclusion
New thiacalix[4]arenes containing amide, hydroxyl and ester frag-
ments, differently substituted at the lower rim were synthesized.
For the synthesis of stereoisomers of p-tert-butyl thiacalix[4]arene
with ester and amide fragments at the lower rim, the template
effect of alkali metal cations was used. Receptor properties of the
newly synthesized thiacalix[4]arene derivatives toward some tetra-
3
3JHH = 7.1 Hz), 4.27 (q, 2H, -O–CH2–CH3, JHH = 7.1 Hz), 4.64
(d, 2H,-O–CH2–CONH, 2JHH = 15.8 Hz), 4.71 (s, 4H, -O–CH2-),
5.86 (d, 2H,-O–CH2–CONH, 2JHH = 15.8 Hz), 6.98 (s, 2H, Ar–H),
7.40 (s, 2H, Ar–H), 7.56, 7.58 AB system (4H, Ar–HA, Ar–HB,
butylammonium salts n-Bu4NX (X = F-, Cl-, Br-, I-, CH3CO2 ,
-
-
-
3
5
4JHH = 2.6 Hz), 7.76 (m, 4H, Ar¢–H, JAB + JAB¢ = 9.1 Hz), 7.99
(m, 4H, Ar¢–H, 3JAB+5JAB¢ = 9.1 Hz), 9.07 s (1H, OH), 10.40 s (2H,
NH). 13C NMR (125 MHz, CDCl3) d (ppm): 14.02, 30.80, 31.19,
34.06, 34.38, 62.10, 72.02, 74.32, 119.34, 120.53, 124.57, 127.80,
128.98, 129.08, 133.39, 134.80, 135.11, 136.00, 143.24, 143.33,
143.60, 147.67, 148.75, 155.26, 155.49, 158.71, 168.47, 169.89.
H2PO4 , NO3 ) were studied by UV spectroscopy. The values of
the association constants (103–105 M-1) of complexes obtained
from derivatives of p-tert-butyl thiacalix[4]arene with tetrabuty-
lammonium salts with 1 : 1 stoichiometry were determined by
electron spectroscopy. It was shown that trisubstituted p-tert-butyl
thiacalix[4]arenes containing secondary amide groups bind anions
more effectively. On an example of p-tert-butyl thiacalix[4]arenes
differently substituted at the lower rim, significant influence of
the number and nature of substituents on the complexation
properties of synthetic receptors was shown. Selective receptors for
fluoride ion and dihydrogen phosphate ion were found. The newly
synthesized compounds can be used to develop sensors for anions
and in the development of systems like an “electronic tongue”.
1
Spectrum H-1H NOESY: H4b/H3, H4¢b/H3¢, H4+b/H3+, H7/H7¢,
H7¢a/H7¢b, H15/H9, H9/H11, H7/H9, H3/H5¢, H7+/H9, H5/H3+. IR
(Nujol) nmax cm-1: 3456, 3319, 3271, 1766, 1698, 1611, 1596, 1555,
1505, 1383, 1340. MS (ESI) m/z = 1162 [M+]. El. Anal. Calcd for
C60H66N4O12S4: C, 59.27; H, 5.29; N, 4.50. Found: C, 60.21; H,
5.72; N, 4.82.
5,11,17,23 - Tetra - tert - butyl - 25, - 27 - bis - [(ethoxycarbonyl) -
methoxy]-26,28-bis-[N -(4¢-nitrophenyl)-aminocarbonylmethoxy]-
thiacalix[4]arene (6). Yield 0.46 g (40%). Mp: 220 ◦C. 1H NMR
(300 MHz, CDCl3) d (ppm): 0.93 (s, 18H, (CH3)3C); 1.31 (s, 18H,
Experimental
General
3
(CH3)3C); 1.19 (t, 6H, -O–CH2–CH3, JHH = 7.2 Hz); 4.09 (q,
Melting points were determined using the Boetius Block appa-
ratus. Most chemicals were purchased from Aldrich and used as
4H, -O–CH2–CH3, 3JHH = 7.2 Hz); 4.53 (s, 4H, -O–CH2–COOEt);
5.35 (s, 4H, -O–CH2–C(O)–NH); 7.01 (s, 4H, Ar–H); 7.74 (s,
3230 | Org. Biomol. Chem., 2011, 9, 3225–3234
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3
4H, Ar–H); 8.15 (AA¢BB¢ system, 8H, Ar¢–H, JAB
+
5JAB¢
=
44.93, 34.40, 61.94, 111.48, 126.32, 138.92, 151.97, 169.70. IR
(Nujol) nmax cm-1: 3356, 1723, 1597, 1542, 1506, 1377, 1336, 1112,
1023. MS (EI) m/z = 224 [M+]. El. Anal. Calcd for C10H12N2O4:
C, 53.57; H, 5.39; N, 12.49. Found: C, 53.53; H, 5.37; N, 12.09.
9.3 Hz); 10.95 (s, 2H, NH). 13C NMR (125 MHz, CDCl3) d (ppm):
14.01, 18.45, 30.90, 31.27, 34.40, 61.49, 72.43, 74.01, 120.71,
124.66, 127.81, 133.17, 136.72, 143.72, 143.99, 147.39, 147.88,
156.13, 158.62, 168.09, 168.65. Spectrum 1H-1H NOESY: H4b/H3,
H4¢b/H3¢, H9/H11, H9/H15, H9¢/H10¢, H7/H7¢, H9/H7¢, H3/H5¢. IR
(Nujol) nmax cm-1: 3261, 1753, 1699, 1611, 1596, 1543, 1518,
1378, 1341. MS (ESI) m/z = 1248 [M+]. El. Anal. Calcd for
C64H72N4O14S4: C, 60.39; H, 5.49; N, 4.23. Found: C, 61.52; H,
5.81; N, 4.48.
N-(4¢-Nitrophenyl)-2-amino-diethylacetate (12). Yield 0.23 g
◦
1
(10%). Mp: 128 C. H NMR (300 MHz, CDCl3) d (ppm): 1.28
3
(t, 6H, -CH2–CH3, JHH = 7.2 Hz), 4.19 (s, 4H, -CH2-), 4.23 (q,
4H, -CH2–CH3, 3JHH = 7.2 Hz), 6.58 (AA¢BB¢ system, 2H, Ar–H,
3JAB+5JAB¢ = 9.2 Hz), 8.11 (AA¢BB¢ system, 2H, Ar–H, 3JAB+5JAB¢
=
9.2 Hz). 13C NMR (125 MHz, CDCl3) d (ppm): 14.04, 14.14, 14.36,
53.37, 53.48, 61.17, 61.64, 61.74, 62.31, 117.37, 125.97, 126.04,
139.03, 152.68, 169.30. IR (Nujol) nmax cm-1: 1748, 1597, 1515,
1486, 1376, 1342, 1116, 1025. MS (EI) m/z = 310 [M+]. El. Anal.
Calcd for C14H18N2O6: C, 54.19; H, 5.85; N, 9.03. Found: C, 53.78;
H, 5.65; N, 8.85.
5,11,17,23-Tetra-tert-butyl-25,-27-bis-[(ethoxycarbonyl)me-
thoxy]-26-[N-(4¢-nitrophenyl)aminocarbonylmethoxy]-28-[N-(4¢¢-
nitrophenyl),-N-(ethoxycarbonylmethyl)-aminocarbonylmethoxy]-
thiacalix[4]arene (7). Yield 0.16 g (14%). Mp: 300 ◦C. 1H NMR
(300 MHz, CDCl3) d (ppm): 0.95 (s, 18H, (CH3)3C), 1.19 (s,
9H, (CH3)3C), 1.25 (s, 9H, (CH3)3C), 1.21 (m, 9H, -CH2–CH3),
4.12 (m, 6H, -CH2–CH3), 4.39 (s, 2H, -N–CH2–C(O)OEt), 5.17
(s, 2H, -O–CH2–C(O)–N–CH2–C(O)OEt), 5.38 (s, 2H, -O–CH2–
C(O)–NH), 4.73, 4.78 (AB system, 2H, HA, HB, -O–CH2–COOEt,
2JHH = 16.5 Hz), 7.07, 7.08 (AB system, 4H, Ar–HA, Ar–HB,
4JHH = 2.6 Hz), 7.42 (s, 2H, Ar–H), 7.63 (s, 2H, Ar–H), 7.62
(AA¢BB¢ system, 2H, Ar¢–H, 3JAB + 5JAB¢ = 8.4 Hz), 8.28 (AA¢BB¢
General procedure for the preparation of compound 10
p-tert-Butylphenol (6 g, 0.04 mol) was suspended in 100 mL of
dry acetone containing a 2.5-fold excess of anhydrous sodium car-
bonate. The mixture was refluxed for 2 h. Then N-(p-nitrophenyl)-
a-bromacetamide (8.3 g, 0.03 mol) and 100 mL of dry acetone
were added. The mixture was refluxed for 33 h. The reaction was
monitored by TLC. After cooling, the solid residue was removed
by filtration. The filtrate was evaporated to dryness. Then, both
solids were treated separately using the same procedure. Solid
was dissolved in 100 ml of chloroform and washed with 50 mL
of 2 M HCl. The organic layer was dried over molecular sieves,
filtered and evaporated under reduced pressure. Crystallization of
the resulting solid from dichloromethane–ethanol mixture gave a
pure sample of 10.
system, 2H, Ar¢–H, 3JAB + 5JAB¢ = 8.4 Hz), 8.21 (AA¢BB¢ system,
3
4H, Ar¢¢–H, JAB
+
5JAB¢ = 9.5 Hz), 11.00 (s, 1H, NH). 13C
NMR (125 MHz, CDCl3) d (ppm): 13.75, 29.09, 29.34, 29.70,
30.61, 30.91, 33.73, 33.88, 34.01, 60.70, 61.15, 71.17, 119.47,
124.48, 124.89, 127.76, 128.04, 132.72, 134.09, 136.13, 136.53,
136.69, 146.71, 146.96, 156.41, 156.80, 168.71, 169.53. Spectrum
1H-1H NOESY: H4b/H3, H4¢b/H3¢, H4+b/H3+, H15/H11+, H14/H12+
,
H9+/H15+, H9+/H11+, H7/H7¢, H7¢/H7+. IR (Nujol) nmax cm-1: 3267,
1747, 1698, 1608, 1596, 1543, 1513, 1377, 1341. MALDI-TOF
MS m/z = 1358 [M+Na]+, 1375 [M+K]+. El. Anal. Calcd for
C68H78N4O16S4: C, 61.15; H, 5.89; N, 4.19; Found: C, 60.65; H,
5.59; N, 4.04.
2-(4-tert-Butylphenoxy)-N-◦(4¢-nitrophen-1¢-yl)acetamide (10).
1
Yield 7.71 g (73%). Mp: 156 C. H NMR (300 MHz, CDCl3) d
(ppm): 1.30 (s, 9H, (CH3)3C), 4.63 (s, 2H, -CH2-), 6.92 (AA¢BB¢
3
5
system, 2H, Ar–H, JAB + JAB¢ = 8.9 Hz), 7.35 (AA¢BB¢ system,
3
5
5,11,17,23 - Tetra - tert - butyl - 25,27 - bis - [(ethoxycarbonyl) -
methoxy] - 26,28 - bis[3¢ - (ethoxycarbonyl) - 2¢ - oxopropoxy] -
thiacalix[4]arene (8). Yield 0.52 g (50%). Mp: 197 ◦C. 1H NMR
(300 MHz, CDCl3) d (ppm): 1.21 (s, 18H, (CH3)3C), 1.25 (s,
2H, Ar–H, JAB + JAB¢ = 8.9 Hz), 7.82 (AA¢BB¢ system, 2H,
3
Ar¢–H, JAB + 5JAB¢ = 9.2 Hz), 8.21 (AA¢BB¢ system, 2H, Ar¢–H,
5
3JAB + JAB¢ = 9.2 Hz), 8.68 (s, 1H, NH). 13C NMR (125 MHz,
CDCl3) d (ppm): 31.45, 34.26, 67.83, 114.42, 119.52, 125.09,
126.81, 142.68, 143.99, 145.74, 154.55, 167.07. IR (Nujol) nmax
cm-1: 3344, 1691, 1612, 1596, 1543, 1508, 1377, 1338, 1112, 1070.
MS (EI) m/z = 328 [M+]. El. Anal. Calcd for C18H20N2O4: C,
65.84; H, 6.14; N, 8.53. Found: C, 65.75; H, 6.07; N, 9.00.
3
18H, (CH3)3C), 1.28 (t, 6H, -CH2–CH3, JHH = 7.1 Hz), 1.32
3
(t, 6H, -CH2–CH3, JHH = 7.3 Hz), 4.23 (q, 4H, -CH2–CH3,
3JHH = 7.1 Hz), 4.25 (q, 4H, -CH2–CH3, JHH = 7.3 Hz), 4.62
3
(s, 4H, -O–CH2-), 4.70 (s, 4H, -O–CH2-), 4.75 (s, 4H, -O–CH2-),
7.47 (s, 4H, Ar–H), 7.52 (s, 4H, Ar–H). 13C NMR (125 MHz,
CDCl3) d (ppm): 14.21, 14.26, 31.02, 31.05, 31.09, 34.17, 34.18,
34.20, 34.23, 60.58, 60.64, 61.51, 67.71, 67.77, 68.19, 68.23, 68.26,
127.63, 127.66, 127.70, 133.49, 133.52, 133.71, 146.22, 146.50,
157.16, 167.25, 167.70, 167.95. Spectrum 1H-1H NOESY: H4b/H3,
H4¢b/H3¢, H7/H5¢, H3/H7¢, H4b/H9¢, H7/H5¢, H3/H7¢. IR (Nujol)
nmax cm-1: 1784, 1766, 1761, 1093. MS (EI) m/z = 1180 [M+]. El.
Anal. Calcd for C60H76O16S4: C, 61.00; H, 6.48. Found: C, 61.22;
H, 6.56.
General procedure for the preparation of compounds 11 and 12
2-(4-tert-Butylphenoxy)-N-(4¢-nitrophen-1¢-yl)acetamide (1 g,
3.05 mmol) was suspended in 30 mL of dry acetone containing
a 4-fold excess of anhydrous potassium or caesium carbonates.
Then a 4-fold excess of ethyl bromoacetate and 40 mL of dry
acetone were added. The mixture was refluxed for 40 or 13 h. The
reaction was monitored by TLC. After cooling, the solid residue
was removed by filtration. The filtrate was evaporated to dryness.
Then, the residue was dissolved in 30 ml of chloroform and was
washed with 30 mL of distilled water. The organic layer was
dried over molecular sieves, filtered and evaporated under reduced
pressure. Crystallization of the resulting solid from ethanol or
diethyl ether gave pure samples of 11 and 12 with 59% and 32%
yields, respectively.
N-(4¢-Nitrophenyl)-2-amino-ethylacetate (11). Yield 0.22 g
(13%). Mp: 130 ◦C. 1H NMR (300 MHz, CDCl3) d (ppm): 1.31 (t,
3H, -CH3, 3JHH = 7.1 Hz), 3.96 (d, 2H, -CH2-), 4.26 (q, 2H, -CH2–
CH3, 3JHH = 7.1 Hz), 5.13 (s, 1H, NH), 6.53 (AA¢BB¢ system, 2H,
Ar–H, 3JAB + 5JAB¢ = 9.0 Hz), 8.08 (AA¢BB¢ system, 2H, Ar–H, 3JAB
+ JAB¢ = 9.0 Hz). 13C NMR (125 MHz, CDCl3) d (ppm): 14.16,
5
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General procedure for the preparation of thiacalix[4]arenes 13–14
TLC. After cooling, the solid residue was removed by filtration.
The filtrate was evaporated to dryness. Then, both solids were
treated separately using the same procedure. Solid was dissolved
in 30 mL of chloroform and was washed with 30 mL of 2 M
HCl. The organic layer was dried over molecular sieves, filtered
and evaporated under reduced pressure. Crystallization of the
resulting solid from chloroform–ethanol or dichloromethane–
ethanol mixture gave pure samples of 6, 16, 17 with 60%, 30%
and 49% or 50% yield, respectively.
Thiacalix[4]arene 5 (0.50 g, 0.43 mmol) or 6 (0.50 g, 0.40 mmol)
was suspended in 30 mL of dry tetrahydrofuran. Then a 4-fold (or
an 8-fold) excess of 2-aminoethanol were added. The mixture was
refluxed for 12 or 30 h. The reaction was monitored by TLC. After
cooling, the solvent of reaction mixture was evaporated to dryness
under reduced pressure. Then crystallization of the resulting solid
from methanol or ethanol gave pure samples of 13–14.
5,11,17,23-Tetra-tert-butyl-25-hydroxy-27-[N-(2-hydroxyethyl)-
carbamoylmethoxy]-26,28-bis[N -(4¢-nitrophenyl)aminocarbonyl-
methoxy]thiacalix[4]arene (13). Yield 0.42 g (98%). Mp: 188 ◦C.
1H NMR (300 MHz, CDCl3) d (ppm): 1.00 (s, 9H, (CH3)3C),
1.07 (s, 18H, (CH3)3C), 1.24 (s, 9H, (CH3)3C), 3.74 (m, 2H, -CH2–
5,11,17,23 - Tetra - tert - butyl - 25,27 - bis - [(ethoxycarbonyl)me -
thoxy] - 26,28 - bis[N - (4¢ - nitrophenyl) aminocarbonylmethoxy] -
thiacalix[4]arene (16). Yield 0.41 g (30%). Mp: 287 ◦C. 1H NMR
(300 MHz, CDCl3) d (ppm): 0.94 (s, 18H, (CH3)3C), 1.34 (s, 9H,
(CH3)3C), 1.37 (s, 9H, (CH3)3C), 1.25 (t, 3H, -O–CH2–CH3, 3JHH
=
CH2-), 3.94 (m, 2H, -CH2–CH2-), 4.19 (s, 1H, -CH2–OH), 4.69 (s,
7.1 Hz), 4.17 (m, 4H, -O–CH2–CH3), 4.67, 5.01 (AB quadruplet,
2
2
2H, –O–CH2–C(O)NH(CH2)2OH, 4.75 (d, 4H, -O–CH2-, JHH
=
4H,-O–CH2–COOEt, JAB = 15.7 Hz), 5.11 (s, 4H, -O–CH2–
15.3 Hz), 5.24 (d, 4H, -O–CH2-, 2JHH = 15.3 Hz), 7.20 (s, 2H, Ar–
4
C(O)NHC6H4NO2), 7.08 (d, 2H, Ar–H, JHH = 2.5 Hz), 7.42 (d,
H), 7.34 (d, 2H, Ar–H, 4JHH = 2.6 Hz), 7.37 (d, 2H, Ar–H, 4JHH
=
4
2H, Ar–H, JHH = 2.5 Hz), 7.43 (s, 2H Ar–H), 7.86 (s, 2H Ar–
H), 7.89 (AA¢BB¢ system, 2H, Ar¢–H, 3JAB + 5JAB¢ = 9.4 Hz), 7.97
(AA¢BB¢ system, 2H, Ar¢–H, 3JAB + 5JAB¢ = 9.4 Hz), 8.15 (AA¢BB¢
2.6 Hz), 7.54 (s, 2H, Ar–H), 7.83 (AA¢BB¢ system, 4H, Ar¢–H,
5
3
3JAB + JAB¢ = 9.1 Hz), 7.97 (t, 1H, -NH–CH2-, JHH = 5.6 Hz),
8.05 (AA¢BB¢ system, 4H, Ar¢–H, 3JAB + 5JAB¢ = 9.1 Hz), 8.51 (s,
1H, -OH), 10.43 (s, 1H, -NH–C6H4–NO2). 13C NMR (125 MHz,
CDCl3) d (ppm): 12.97, 13.89, 30.84, 31.29, 34.33, 40.30, 40.54,
73.04, 73.82, 76.75, 77.26, 120.82, 124.49, 128.24, 132.38, 136.82,
3
system, 2H, Ar¢–H, JAB+5JAB¢ = 9.4 Hz), 8.21 (AA¢BB¢ system,
3
2H, Ar¢–H, JAB+5JAB¢ = 9.4 Hz), 10.63 (s, 1H, NH), 10.70 (s,
1H, NH). 13C NMR (125 MHz, CDCl3) d (ppm): 18.89, 35.67,
36.04, 38.84, 39.08, 44.30, 44.64, 44.81, 44.97, 45.31, 65.83, 74.76,
123.92, 124.24, 130.65, 130.94, 132.51, 133.42, 147.70, 147.96,
143.45, 144.32, 146.97, 147.18, 156.50, 159.07, 166.58, 168.37.
1
Spectrum H-1H NOESY: H3/H4b, H5/H4b, H3¢/H4¢b, H3+/H4+b
,
1
151.63, 152.16, 161.40, 171.67, 173.05, 173.46. Spectrum H-1H
H3/H5¢, H3¢/H5, H5/H3+, H9/H11, H11/H12, H10¢/H11¢. IR (Nujol)
nmax cm-1: 3600, 3371, 3278, 1662, 1552, 1512, 1377, 1342, 1303.
MALDI-TOF MS m/z = 1178 [M+H]+, 1200 [M+Na]+, 1216
[M+K]+. El. Anal. Calcd for C60H67N5O12S4: C, 61.15; H, 5.73;
N, 5.94. Found: C, 60.84; H, 5.74; N, 5.94.
NOESY: H4¢b/H9+, H9¢/H10¢, H5¢/H7+, H4¢b/H3¢, H4¢b/H5¢, H4+b/H3+,
H4b/H3, H5¢/H9+, H9¢/H3+, H7¢/H3+. IR (Nujol) nmax cm-1: 3271,
1750, 1706, 1611, 1596, 1548, 1511, 1376, 1341. MALDI-TOF
MS m/z = 1249.5 [M+H]+, 1271.5 [M+Na]+, 1287.5 [M+K]+. El.
Anal. Calcd for C64H72N4O14S4: C, 61.40; H, 6.01; N, 4.46; S, 10.32.
Found: C, 61.59; H, 6.34; N, 4.36; S, 10.62.
5,11,17,23-Tetra-tert-butyl-25,27-bis[N-(2-hydroxyethyl)carba-
moylmethoxy] - 26,28 - bis[N - (4¢ - nitrophenyl) aminocarbonyl -
methoxy]thiacalix[4]arene (14). Yield 0.25 g (48%). Mp: 148 ◦C.
1H NMR (300 MHz, CDCl3) d (ppm): 1.09 (s, 18H, (CH3)3C),
1.14 (s, 18H, (CH3)3C), 3.38 (m, 4H, -CH2–CH2-), 3.84 (m, 4H,
-CH2–CH2-), 4.84 (s, 4H, -O–CH2–C(O)NH(CH2)2OH), 4.99 (t,
2H, -OH, 3JHH = 5.0 Hz), 5.23 (s, 4H, -O–CH2-), 7.34 (s, 4H, Ar–
5,11,17,23-Tetra-tert-butyl-25,-27-bis-[(ethoxycarbonyl)me-
thoxy] - 26,28 - bis[N - (4¢ - nitrophenyl) aminocarbonylmethoxy] -
thiacalix[4]arene (17). Yield 0.67 g (50%). Mp: 234 ◦C. 1H NMR
(300 MHz, CDCl3) d (ppm): 0.66 (s, 18H, (CH3)3C), 1.29 (s, 18H,
(CH3)3C), 1.25 (t, 6H, -O–CH2–CH3, 3JHH = 7.1 Hz), 4.19 (q, 4H,
-O–CH2–CH3, 3JHH = 7.1 Hz), 4.62 (s, 4H,-O–CH2–COOEt), 4.79
(s, 4 H, -O–CH2–C(O)–NH), 7.24 (s, 4H, Ar–H), 7.58 (s, 4H, Ar–
H), 7.74 (AA¢BB¢ system, 4H, Ar¢–H, 3JAB + 5JAB¢ = 9.4 Hz), 8.19
H), 7.40 (s, 4H, Ar–H), 7.90 (AA¢BB¢ system, 4H, Ar¢–H, 3JAB
+
=
3
5
5JAB¢ = 9.1 Hz), 8.21 (AA¢BB¢ system, 4H, Ar¢–H, JAB + JAB¢
9.1 Hz), 8.28 (t, 2H, -NH–CH2-, 3JHH = 5.3 Hz), 10.49 (s, 2H, -NH–
C6H4–NO2). 13C NMR (125 MHz, CDCl3) d (ppm): 31.03, 31.11,
34.40, 42.18, 60.58, 74.88, 76.75, 77.26, 119.42, 125.10, 127.73,
135.10, 136.25, 143.86, 148.22, 168.16. Spectrum 1H-1H NOESY:
H3/H4b, H3¢/H4¢b, H3/H5¢, H7/H7¢, H7/H9, H10¢/H11¢, H11/H12. IR
(Nujol) nmax cm-1: 3400, 3346, 1651, 1544, 1515, 1302, 1377, 1342,
1056. MALDI-TOF MS m/z = 1279 [M+H]+, 1301 [M+Na]+,
1317 [M+K]+. El. Anal. Calcd for C64H74N6O14S4: C, 60.08; H,
5.83; N, 6.57. Found: C, 59.80; H, 5.80; N, 6.54.
3
5
(AA¢BB¢ system, 4H, Ar¢–H, JAB + JAB¢ = 9.4 Hz), 9.08 (s, 2H,
NH). 13C NMR (125 MHz, CDCl3) d (ppm): 14.18; 30.37; 30.54;
30.72; 30.85; 30.95; 31.06; 33.97; 34.35; 60.78; 65.85; 70.46; 119.49;
124.96; 125.03; 125.78; 128.31; 128.44; 128.60; 133.04; 133.26;
143.08; 143.83; 147.67; 147.85; 155.61; 155.99; 167.17; 167.47.
1
Spectrum H-1H NOESY: H4b¢/H9, H4b¢/H7, H4b/H9¢, H4b¢/H11,
H4b/H7¢, H4b/H7¢. IR (Nujol) nmax cm-1: 3259, 1766, 1697, 1613,
1598, 1541, 1513, 1377, 1343. MALDI-TOF MS m/z = 1249.8
[M+H]+, 1271.7 [M+Na]+, 1287.7 [M+K]+. El. Anal. Calcd for
C64H72N4O14S4: C, 61.40; H, 6.01; N, 4.46; S, 10.32. Found: C,
61.59; H, 6.34; N, 4.36; S, 10.62.
General procedure for the preparation of thiacalix[4]arenes 6,
16–17
General procedure for the preparation of thiacalix[4]arenes 18–20
Thiacalix[4]arene 15 (1 g, 1.12 mmol) was suspended in 40 mL
of dry acetone containing a 4-fold excess of an anhydrous
alkali carbonate. Then N-(p-nitrophenyl)-a-bromacetamide (1.2
g, 4.48 mmol) and 20 mL of dry acetone were added. The
mixture was refluxed for 60 h. The reaction was monitored by
Thiacalix[4]arene 2 (1 g, 0.93 mmol) was suspended in 30 mL of
dry acetone containing a 3-fold (or a 8-fold) excess of an anhydrous
alkali carbonate. Then a 4-fold (or a 8-fold) excess of N,N-
diethylbromoacetamide and 40 mL of dry acetone were added.
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The mixture was refluxed for several hours. The reaction was
monitored by TLC. After cooling, the solid residue was removed
by filtration. The filtrate was evaporated to dryness. Then, both
solids were treated separately using the same procedure. Solid was
dissolved in 30 ml of chloroform and was washed with 30 mL
of 2 M HCl. The organic layer was dried over molecular sieves,
filtered and evaporated under reduced pressure. Crystallization of
the resulting solid from chloroform–ethanol or dichloromethane–
ethanol mixture gave pure samples of 18–20.
thiacalix[4]arene (20). Yield 0.18 g (15%). Mp: 183 ◦C. 1H NMR
(300 MHz, CDCl3) d (ppm): 0.86 (s, 18H, (CH3)3C), 0.98 (t, 3H,
-O–CH2–CH3, 3JHH = 7.1 Hz), 1.14 (t, 3H, -O–CH2–CH3, 3JHH
=
=
3
7.1 Hz), 1.34 (s, 18H, (CH3)3C), 3.00 (q, 2H, -CH2–CH3, JHH
3
7.1 Hz), 3.36 (q, 2H, -CH2–CH3, JHH = 7.1 Hz), 4.74 (s, 4H,
-OCH2CONEt2), 5.43 (s, 4H, -OCH2CONH-), 6.90 (s, 4H, Ar–
3
H), 7.81 (s, 4H, Ar–H), 8.16 (AA¢BB¢system, 8H, Ar¢–H, JAB
+
5JAB¢ = 9.6 Hz), 11.30 (s, 2H, NH). 13C NMR (125 MHz, CDCl3)
d (ppm): 30.98, 31.27, 34.32, 42.03, 61.99, 73.91, 75.60, 119.55,
120.92, 124.76, 127.98, 128.50, 134.16, 134.33, 135.21, 135.50,
143.42, 143.67, 148.41, 149.03, 155.40, 157.49, 167.65, 169.59.
Spectrum 1H-1H NOESY: H7/H7¢, H9¢/H10¢, H3/H4b, H3¢/H4¢b,
H11/H10¢, H12/H10¢, H11/H9¢, H12/H9¢, H9/H11, H7/H9, H7¢/H9. IR
(Nujol) nmax cm-1: 3373, 1656, 1638, 1546, 1735, 1509, 1545, 1330,
1378, 1112, 1096. MALDI-TOF MS m/z = 1325.66 [M+Na]+. El.
Anal. Calcd for C68H82N6O12S4: C, 62.65; H, 6.34; N, 6.45. Found:
C, 62.53; H, 6.14; N, 6.45.
5,11,17,23-Tetra-tert-butyl-25-hydroxy-26,28-bis[N-(4¢-nitro-
phenyl)-aminocarbonylmethoxy]-27-[N,N -diethylcarbamoylme-
thoxy]-thiacalix[4]arene (18). Yield 0.86 g (78%). Mp: 256 ◦C.
1H NMR (300 MHz, CDCl3) d (ppm): 0.68 (s, 9H, (CH3)3C),
1.05 (s, 9H, (CH3)3C-), 1.30 (t, 3H, -O–CH2–CH3, 3JHH = 7.1 Hz),
1.31 (t, 3H, -O–CH2–CH3, 3JHH = 7.1 Hz), 1.34 (s, 18H, (CH3)3C),
3.27 (q, 2H, -CH2–CH3, 3JHH = 7.1 Hz), 3.58 (q, 2H, -CH2–CH3,
2
3JHH = 7.1 Hz), 4.63 (d, 2H, -OCH2CONH-, JHH = 16.0 Hz),
4.74 (s, 2H, -OCH2CONEt2), 6.36 (d, 2H, -OCH2CONH-, 2JHH
=
Materials and general methods
16.0 Hz), 6.76 (s, 2H, Ar–H), 7.27 (s, 2H, Ar–H), 7.71 and 7.80
(AB quadruplet, 4H, Ar–HA, Ar–HB, 4JHH = 2.5 Hz), 7.76 (AA¢BB¢
system, 4H, Ar¢–H, 3JAB + 5JAB¢ = 9.1 Hz), 7.93 (AA¢BB¢ system,
The studies of the receptor properties of thiacalix[4]arene deriva-
tives 2–6, 10, 13, 14, 16–20 were carried out in CHCl3 (analytical
grade). UV spectra were obtained on a Perkin Elmer spectropho-
tometer Lambda 35.
3
5
4H, Ar¢–H, JAB + JAB¢ = 9.1 Hz), 9.47 (s, 1H, -OH), 10.97 (s,
2H, NH). 13C NMR (125 MHz, CDCl3) d (ppm): 13.00, 14.22,
30.67, 31.35, 34.43, 41.17, 73.51, 74.52, 119.39, 124.34, 128.43,
129.80, 132.79, 135.05, 135.39, 136.91, 143.01, 144.11, 147.25,
Determination of the stoichiometry by isomolar series method
1
148.51, 155.26, 155.62, 159.67, 166.47, 169.18. Spectrum H-1H
The series of experiments with the constant total concentration of
guest and host molecules (0.02 M) and various guest/host ratio
was prepared and processed as described earlier.33
NOESY: H7/H9¢, H7/H7¢, H7/H10¢, H3/H4b, H3¢/H4¢b, H3+/H4+b
,
H7/H9, H7+/H9, H3/H5¢, H5/H3+. IR (Nujol) nmax cm-1: 3274,
3397, 1717, 1641, 1597, 1738, 1545, 1511, 1330, 1378, 1110, 1096.
MALDI-TOF MS m/z = 1190.56 [M+H]+, 1212.55 [M+Na]+,
1228.57 [M+K]+. El. Anal. Calcd for C62H71N5O11S4: C, 62.55; H,
6.01; N, 5.88. Found: C, 62.42; H, 5.87; N, 5.83.
Experimental methods of determination of the association constant
Absorption properties of compounds were studied in chloroform
solution (2.5 ¥ 10-5 M). The efficiency of anion binding was
estimated by addition of a 200-fold excess of tetrabutylammonium
salt in chloroform. The concentration of the anion in titration
experiment was varied from 2.5 ¥ 10-5 M to 5.0 ¥ 10-3 M. The
association constants were determined as described earlier.33
5,11,17,23-Tetra-tert-butyl-25-hydroxy-26,28-bis[N-(4¢-nitro-
phenyl) - aminocarbonylmethoxy] - 27 - [N,N - diethylcarbamoyl -
methoxy]-thiacalix[4]arene (19). Yield 0.44 g (40%). Mp: 168 ◦C.
1H NMR (300 MHz, CDCl3) d (ppm): 0.35 (t, 3H, -O–CH2–CH3,
3JHH = 7.0 Hz), 1.04 (s, 9H, (CH3)3C-), 1.07 (t, 3H, -O–CH2–CH3,
3JHH = 7.0 Hz), 1.15 (s, 18H, (CH3)3C), 1.31 (s, 9H, (CH3)3C),
2.91 (q, 2H, -CH2–CH3, 3JHH = 7.0 Hz), 3.27 (q, 2H, -CH2–CH3,
Acknowledgements
2
3JHH = 7.0 Hz), 4.43 (d, 2H, -OCH2CONH-, JHH = 15.1 Hz),
The financial support from Federal Program “Research and
scientific-pedagogical cadres Innovative Russia” in 2009-2013
years (No P1107 on 26 August 2009), RFBR (09-03-00426,
10-03-92661-NSF) and the Program of the President of the
Russian Federation for the State support of young Russian
scientists – Doctors of Sciences (MD-2747.2010.3) is gratefully
acknowledged. The authors thank Dr Larry W. Daniel from Wake
Forest University (Winston–Salem, North Carolina, USA) for
comments and discussion of the manuscript.
4.70 (s, 2H, -OCH2CONEt2), 5.11 (d, 2H, -OCH2CONH-, 2JHH
=
15.1 Hz), 7.65 (s, 2H, Ar–H), 7.71 (s, 2H, Ar–H), 7.41 and 7.55
(AB quadruplet, 4H, Ar–HA, Ar–HB, 4JHH = 2.5 Hz), 7.46 (s, 1H, -
OH), 7.68 (AA¢BB¢ system, 4H, Ar¢–H, 3JAB + 5JAB¢ = 9.1 Hz), 8.07
3
5
(AA¢BB¢ system, 4H, Ar¢–H, JAB + JAB¢ = 9.1 Hz), 9.80 (s, 2H,
-NH-). 13C NMR (125 MHz, CDCl3) d (ppm): 30.83, 30.94, 31.37,
34.25, 34.44, 69.61, 72.93, 119.20, 121.31, 124.92, 127.10, 128.20,
132.37, 133.38, 134.88, 135.00, 143.14, 143.75, 144.53, 147.88,
1
148.91, 155.00, 156.45, 158.08, 165.65, 166.73. Spectrum H-1H
NOESY: H7¢/H4b, H7/H4¢b, H9¢/H4b, H7/H5¢, H7/H9, H10¢/H4b,
H9¢/H10¢. IR (Nujol) nmax cm-1: 3301, 3404, 1730, 1616, 1622, 1733,
1512, 1549, 1378, 1340, 1111; 1075. MALDI-TOF MS m/z =
1190.58 [M+H]+, 1212.57 [M+Na]+, 1228.55 [M+K]+. El. Anal.
Calcd for C62H71N5O11S4: C, 62.55; H, 6.01; N, 5.88. Found: C,
61.84; H, 6.03; N, 5.78.
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