The synthesis of p-tert-butyl thiacalix[4]arenes functionalized with secondary amide groups at the lower rim and their extraction properties and self-assembly into nanoscale aggregates

Article abstract of DOI:10.1016/j.tet.2008.05.057

In this work, the synthesis of novel p-tert-butyl thiacalix[4]arenes functionalized with the secondary amide groups at the lower rim in cone, partial cone, and 1,3-alternate conformations is described. The ability of novel thiacalixarene derivatives to fo

Full text of DOI:10.1016/j.tet.2008.05.057

Tetrahedron 64 (2008) 7112–7121
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journal homepage: www.elsevier.com/locate/tet
The synthesis of p-tert-butyl thiacalix[4]arenes functionalized with
secondary amide groups at the lower rim and their extraction properties
and self-assembly into nanoscale aggregates
,
a
a
b
a
Ivan I. Stoikov a , Elena A. Yushkova , Arkadij Yu Zhukov , Ilya Zharov , Igor S. Antipin ,
*
Alexander I. Konovalova
a Kazan State University, A.M. Butlerov Chemical Institute, 420008 Kazan, Kremlevskaya, 18, Department of Chemistry, Russian Federation
b University of Utah, Salt Lake City, UT 84112, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work, the synthesis of novel p-tert-butyl thiacalix[4]arenes functionalized with the secondary
amide groups at the lower rim in cone, partial cone, and 1,3-alternate conformations is described. The
ability of novel thiacalixarene derivatives to form dimeric associates held together by hydrogen bonds of
Received 14 February 2008
Received in revised form 29 April 2008
Accepted 15 May 2008
p-tert-butyl thiacalixarenes and to recognize metal ions of s (Liþ, Naþ, Kþ, Csþ, Mg2þ, Ca2þ, Ba2þ), p (Al3þ
,
Available online 17 May 2008
Pb2þ), and d (Fe3þ, Co3þ, Ni2þ, Cu2þ, Agþ, Cd2þ, Hg2þ) elements was investigated by the picrate extraction
method and dynamic light scattering (DLS). As was established, the thiacalix[4]arenes investigated are
poor extractants for all the metal ions. Meanwhile they self-associate to form dimers of similar size (1.1–
2.7 nm) and nanoscale particles consisting of p-tert-butyl thiacalix[4]arenes and silver cations with hy-
drodynamic diameters of 70–170 nm.
Keywords:
Self-assembly
p-tert-Butyl thiacalix[4]arenes
Molecular recognition
Picrate extraction
Ó 2008 Elsevier Ltd. All rights reserved.
Dynamic light scattering (DLS)
1. Introduction
acceptor, and some lipophilic interactions between various sub-
stituents.3,21 The dimeric covalent binding3,17,31,32 and self-assem-
The design and synthesis of a variety of host molecules is an
interesting topic in the field of supramolecular chemistry1,2 because
of the specified applications of these novel compounds3 and ne-
cessity of the basic research of molecular recognition,4–6 self-as-
sembly,7–10 and self-organizing11,12 processes. These synthetic
receptors are irreplaceable as base elements in the development of
sensors,13–15 and as selective carriers in industrial membrane ex-
traction technologies,4,16,17 highly affine and convertible effec-
tors,18–20 and catalysts.21 One of the popular molecular platforms
for the design of molecular receptors is the calix[4]arene.22,23 The
advantage of the host molecules consisting of the modification at
the upper and lower rim of the appropriate macrocyclic platform24
and the replacement of original methylene bridges between the
aromatic units in calixarenes by sulfur,24–26 nitrogen,3,27 and sili-
con28 atoms allows varieties of the receptor properties of these
molecules over a wide range. Besides, the calix[4]arenes are able to
form supramolecular aggregates consisting of two, three or more
receptor molecules.29,30 The ability of the host molecules to self-
bling33–35 associates of the calix[4]arene derivatives are able to
selectively include various substrates. This makes it possible to use
them as containers for sensing, fixation, and storage of molecules.17
In this work, we describe the synthesis of novel p-tert-butyl thia-
calix[4]arenes functionalized with secondary amide groups at the
lower rim in cone, partial cone, and 1,3-alternate conformations and
study the ability of these molecules both to form dimeric associates,
which are held together by a seam of hydrogen bonds of p-tert-
butyl thiacalix[4]arenes and to recognize metal ions of s (Liþ, Naþ,
Kþ, Csþ, Mg2þ, Ca2þ, Ba2þ), p (Al3þ, Pb2þ), and d (Fe3þ, Co3þ, Ni2þ
,
Cu2þ, Agþ, Cd2þ, Hg2þ) elements as shown by the picrate extraction
method and dynamic light scattering (DLS).
2. Results and discussion
2.1. Synthesis of stereoisomers of tetrasubstituted at the
lower rim p-tert-butyl thiacalix[4]arenes containing
secondary amide fragments
assemble is caused by H-bonding, van der Waals,
p–p, donor–
Thiacalix[n]arenes provide a unique opportunity to modify the
macrocyclic platform and a wide variation of hydrophilic–lipophilic
properties. This is especially important because the selective
* Corresponding author. Tel.: þ7 8432 315463; fax: þ7 8432 752253.
E-mail address: ivan.stoikov@mail.ru (I.I. Stoikov).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.057

I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
7113
- direct interaction of the initial macrocycle 1 with an appro-
priate alkylation agent (Fig. 1a);41,42
modification at the upper rim of a macrocyclic platform by suitable
heteroatom groups often increases the efficiency and selectivity of
the linkage for the macrocycles.26 Thus, the introduction of sec-
ondary amide groups at the lower rim of the p-tert-butyl thiaca-
lix[4]arenes 1–5 should result in a decrease of both n-donor ability
and steric congestion of the amide fragments.36,37 This leads to an
increase in the efficiency of the binding of p and d metal cat-
ions.36,37 Meanwhile, the lesser electron donation properties of the
carbonyl fragments should result in a change of the binding effec-
tiveness toward alkali and alkaline earth metal cations.38 The re-
ceptor molecules substituted with amide containing groups are
able to form intra and/or intermolecular hydrogen bonds between
H-donating NH-fragments and carbonyl groups.39,40
It is very difficult to predict the influence of the association of
the secondary amide fragments on the receptor properties of p-
tert-butyl thiacalix[4]arenes functionalized with amide groups at
the lower rim in three conformations owing to the influence of two
factors, namely, the competition of NH-fragments with the metal
cations for the lone pair of the carbonyl groups and the spatial pre-
organization of the amide groups.
- modification of thiacalix[4]arene based tetraether stereoiso-
mers (Fig. 1b).43,44
The first approach makes it possible to significantly shorten the
synthetic path to the target compound but requires special selec-
tion of experimental conditions to obtain a certain stereoisomer for
each alkylation agent. In addition, collateral reactions may occur
when thiacalix[4]arenes with secondary amide groups are
obtained. We have therefore chosen the two-stage strategy for
synthesis of thiacalix[4]arene derivatives containing amide func-
tions. In the first step, the initial macrocycle 1 was alkylated with
bromoethylacetate in the presence of the alkali metal carbonates,
which determined the appropriate conformation (cone, partial cone
and 1,3-alternate) of the thiacalix[4]arene macrocycle. In the sec-
ond step, the stereoisomers of tetraesters 2 obtained were modified
to the corresponding p-tert-butyl thiacalix[4]arene derivatives.
The capability of the receptor to bind a substrate is defined by
the spatial location of the binding site and by its chemical nature.
The relative position of the amide groups of p-tert-butyl thia-
calix[4]arene derivatives is defined by the conformation of the
There are two approaches to obtain stereoisomers of tetraamides
on the basis of thiacalix[4]arene 1 described in the literature:
R'
N
R'
N
R
N
CO
R
OC
R'
CO
R
O
O
O
O
O
O
N
O
O
OC
O
O
N
OC
OC
R
O
N
R
cone
N
R'
CO
O
OC
N
R'
OC
R
R
CO
R
N
R'
CO
N
R'
N
R
CO
R'
R'
R
R
N
R
R'
R'
R'
1,3-alternate
partial cne
a
OH
S
S
S
S
OH HO
OH
OH
HO
OH
OH
b
EtO2C
O
CO2Et
O
CO2Et
O
O
O
O
O
O
O
CO Et
O
2
CO2Et
CO2Et
O
O
EtO2C
CO2Et
CO2Et
CO2Et
CO2Et
R'
EtO2C
R'
R
R'
R
N
R
N
N
CO
OC
CO
O
O
O
O
O
O
OC
O
O
OC
O
O
OC
N
N
O
O
CO
R
OC
OC
R
N
R'
CO
R
R'
R
N
R'
N
CO
N
R'
CO
R'
N
R'
R
R
R
N
R
N
R'
R'
R
cone
R'
1,3-alternate
partial cone
Figure 1. Scheme of synthesis of amide stereoisomers on the basis of thiacalix[4]arene.

7114
I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
t-Bu
of the tertiary amide group of the thiacalix[4]arene derivative with
t-Bu
a secondary one may reduce the efficiency of cation binding. It can
be assumed that, the secondary amides on the basis of p-tert-butyl
thiacalix[4]arene (Fig. 1, R¼H) will show selective binding of se-
lected metal cations. The introduction of different substituents to
the amide group will give thiacalix[4]arene derivatives, which
b
NH2-R
t-Bu
S
S
4
4
O
a
O
C
CO2Et
1) SOCl2
2) NH2-R, NEt3
1) OH-
2) H+
O
NH
R
2
S
differ in their p-donor and lipophilic abilities.
4
O
To obtain the amides on the basis of the p-tert-butyl thiaca-
lix[4]arene from precursors 2 two approaches can be used: (a) the
hydrolysis of the stereoisomers of tetraethers 2 to appropriate
tetraacids 3 followed by their conversion to chloroanhydrides and
then to amides in the presence of a base to neutralize the educed
HCl47 and (b) direct interaction of appropriate amines with tetra-
ethers 248 (Fig. 2).
3
CO2H
Figure 2. Synthetic approaches to the synthesis of amides on the basis of
thiacalix[4]arene.
macrocycle ring. The variation of different substituents at the ni-
trogen atom of the amide groups (Fig. 1, R, R0) provides the possi-
bility to change p-donor ability and steric capacity of amide groups,
as well as the acidity of the amide protons (in the case of the sec-
ondary amides). Additional centers coordinating the substrate can
also be incorporated in the fragments R and R0 (Fig. 1).
Three isomeric acids 349 were transformed to corresponding
chloroanhydrides by boiling in SOCl2 (see Scheme 1). Tetraamides
4–6 were obtained by interaction of a number of primary amines
(aniline, benzylamine, and n-octylamine) with chloroanhydrides of
tetraacid stereoisomers 3 in the presence of triethylamine in
methylene chloride. Then they were isolated by recrystallization
from a mixture of ethanol and methylene chloride. The reaction
yields ranged from 72 to 94% (Table 1).
It is known that the receptors, which effectively bind groups of
cations show low selectivity toward individual cations.45 This is
true also for tertiary amides based on p-tert-butyl thiacalix[4]arene,
which are effective receptors for metal cations.41,46 However, it
should be mentioned that the secondary amide fragment is the less
1H and 13C NMR spectra of the compounds obtained corre-
sponded to the structure of the stereoisomers of thiacalix[4]arene
tetraamides. It should be emphasized that the adsorption band of
associated amide group (3300–3250 cmꢀ1) was present in the IR
effective
p
-donor than the tertiary amide.45 Thus, the substitution
O
O
O
O
O
O
O
O
O
S
S
S
S
S
S
O
S
O
S
S
S
S
S
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
i
i
i
2 c
2 b
2 a
OH
OH
O
HO
O
O
O
O
O
S
S
S
S
S
S
O
S
O
S
S
S
S
S
O
O
O
O
O
O
O
O
O
O
O
O
OH
OH
HO
3 b
HO
O
HO
OH
O
O
O
HO
HO
3 c
HO
3 a
ii
ii
ii
R
R
R
HN
HN
HN
O
O
O
O
O
O
S
S
S
S
S
S
O
S
O
S
S
S
S
S
O
O
O
O
O
O
O
O
O
O
O
O
O
HN
R
NH
R
NH
O
O
NH
HN
O
HN
NH
HN
HN
R
R
R
R
R
R
R
4 c: R=
4 a: R=
4 b: R=
5 c: R=
6 c: R=
5 a: R=
5 b: R=
6 b: R=
6 a: R=
cone
partial cone
1,3-alternate
Scheme 1. Reagents and conditions: (i) LiOH, H2O/THF; HCl; (ii) SOCl2, reflux; RH, NEt3,CH2Cl2, rt.

I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
7115
Table 1
Table 2
Compound yields 4–6 (%)
Yields of products in the aminolysis reaction of the esters 2 (%)
4
5
6
Compound, R¼
cone
partial cone
1,3-alternate
cone
partial cone
1,3-alternate
94
92
90
90
90
89
75
76
72
6, C8H17
7, C12H25
8, C18H37
95
92
92
86
91
96
89
93
81
spectra of all the conformers of the compounds 4–6. The peak of
molecular ion was also found in the mass spectra of the compounds
4–6.
of aminolysis we suggest has some advantage over that published
by Lhotak group,43,44 i.e., higher yields of the target products (81–
96%) and simpler treatment of the reaction mixture. Individual
products were isolated by washing the reaction mixture with the
water/ethyl alcohol mixture. Nevertheless, it should be mentioned
that the use of labor-intensive procedure of the reaction mixture
treatment as well as lower yields of the target products in Lhotak’s
investigation can be related to the use of bifunctional amines as
initial compounds.
The method proposed in this work for the synthesis of tetraa-
mides on the basis of p-tert-butyl thiacalix[4]arene can be used
only for the primary amines, which act as active nucleophiles. The
side reactions under rather severe conditions of aminolysis (150 ꢁC)
prevent from the use of amines containing reactive functional
groups in the side chains in the aminolysis of the stereoisomers of
tetraethers of thiacalix[4]arene 2.
To reduce the steps in the synthetic path to the target products,
we have investigated the synthesis of amides on the basis of thia-
calix[4]arene by the aminolysis of the stereoisomers of appropriate
tetraethers 2 (Scheme 2, Fig. 2). For carbon acid amides, this is
a classical reaction of organic chemistry.50 However, it should be
mentioned that the reactivity of functional groups in macrocyclic
compounds often dramatically differs from that of analogs.45 We
investigated the interaction of the stereoisomers of tetraethers 2
with primary aliphatic amines (n-octyl-, n-dodecyl-, and n-octa-
decylamine) in the presence of ammonium chloride.
The yield of target compounds obtained by aminolysis depends
on the temperature of the reaction mixture and on the excess of the
primary amine (Scheme 2). From the room temperature up to
100 ꢁC, no changes in the reaction mixture composition were ob-
served. Increasing the temperature up to 150 ꢁC and the use of the
5-fold excess of the amine resulted in the formation of the mac-
rocycles 6–8 with high yields of 81–96% (Table 2). With the lesser
excess (to two amine equivalents per each ester group) or higher
temperature inseparable mixture of the products was obtained. The
yields of the compounds 6 obtained by the aminolysis of tet-
raethers 2 with n-octylamine were found to be higher than those of
the two-stage synthesis of these compounds (Table 2).
The structure and the composition of the amides on the basis of
thiacalix[4]arene obtained in the present work were determined by
elemental analysis and by 1H and 13C NMR spectroscopy, IR-spec-
troscopy, and mass-spectrometry.
The spectral characteristics of the tetraoctylamides 6 obtained
by the aminolysis of the stereoisomer of the tetraether 2 and syn-
thesized from tetraacids via chloranhydride 3 are similar, and hence
the conformation of the macrocycle ring does not change under
conditions of aminolysis of tetraether 2 with n-octylamine. The
attribution of the macrocycle ring conformation of amides 7 and 8
can be made by the comparison of their 1H NMR spectra with those
of the amides 6.
The synthesis of tetraamides on the basis of thiacalix[4]arene by
aminolysis of the stereoisomers of tetraethers 2 has been already
described in the works of Lhotak group.43,44 The interaction of the
stereoisomers of tetraethers 2 with a range of aliphatic diamines
led to the products of the intra-molecular cyclization. The method
Considering the 1H NMR spectra of the compounds 6–8 in more
detail, for all the three compounds (cone conformation) the protons
O
O
O
O
O
O
O
S
O
O
S
S
S
S
S
O
S
O
S
S
S
S
S
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
2 c
2 b
i
i
i
2 a
R
R
R
HN
HN
HN
O
O
O
O
O
O
S
S
S
S
S
S
O
S
O
S
S
S
S
S
O
O
O
O
O
O
O
O
O
O
O
O
O
R
HN
R
NH
R
NH
O
O
NH
HN
O
HN
NH
HN
HN
R
R
R
R
R
R
6 c: R=
7 c: R=
8 c: R=
6 a: R=
7 a: R=
8 a: R=
6 b: R=
7 b: R=
8 b: R=
cone
partial cone
1,3-alternate
Scheme 2. Reagents and conditions: (i) RNH2, NH4Cl, 150 ꢁC.

7116
I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
Table 3
Percent of extraction (%E) of metal ions by conformational isomers of the thiacalix[4]arene derivatives 4–8
Agþ
Liþ
Naþ
Kþ
Csþ
Mg2þ
Ca2þ
Ba2þ
Al3þ
Fe3þ
Ni2þ
Cu2þ
Co3þ
Pb2þ
Hg2þ
Cd2þ
Absorption with CH2Cl2
cone-4
partial cone-4
1,3-alternate-4
cone-5
partial cone-5
1,3-alternate-5
cone-6
partial cone-6
1,3-alternate-6
cone-7
partial cone-7
1,3-alternate-7
cone-8
partial cone-8
1,3-alternate-8
4
6
4
11
8
5
7
11
8
22
11
10
18
36
3
1
1
1
3
1
1
1
1
1
9
1
2
2
35
3
5
2
0
2
5
1
1
1
1
1
11
1
1
3
25
1
1
3
1
1
1
1
1
5
2
8
2
1
3
30
2
6
1
2
1
4
2
2
1
2
1
10
1
1
3
25
1
1
4
2
4
2
2
2
1
3
11
4
5
7
47
3
0
1
1
2
3
1
1
1
4
8
1
3
5
30
2
4
1
2
2
2
2
1
1
1
3
9
1
3
3
33
2
4
6
7
6
9
7
6
5
6
7
21
4
9
14
48
8
28
25
33
36
25
27
31
29
30
38
27
27
29
54
28
37
5
6
5
8
5
5
5
4
8
21
3
5
8
52
6
3
5
8
9
6
5
6
5
7
19
5
8
10
49
7
5
4
7
9
5
4
5
5
7
22
5
7
10
38
8
6
5
5
8
4
5
6
6
6
21
6
7
11
52
7
10
10
9
13
10
10
12
10
9
22
13
9
17
32
16
19
5
8
5
9
5
4
6
5
4
17
5
4
10
53
9
16
8
4
7
15
12
10
11
13
14
Extraction condition: [L]org.,init¼2.5ꢂ10ꢀ3 M, [MPic]aq,init.¼2.32ꢂ10ꢀ4 M.46
of the tert-butyl groups and those of aliphatic radicals in the amide
groups (excluding the protons of the methylene groups at the ni-
trogen atom, which are shown as multiplet at 3.25 ppm) give a set
of signals from 0.8 to 1.7 ppm. The singlet at 4.1 ppm corresponds to
the oxymethylene fragment of the substituents. The aromatic
protons of aryl groups of the macrocycle give a singlet at 7.54 ppm.
The triplet at 7.8 ppm corresponds to the protons of the amide
groups.
IR spectra of the compounds 1,3-alternate-(6–8) are similar to
each other. There are absorption bands of carbonyl groups (1649–
1654 cmꢀ1), of associated and none-associated amide protons and
absorption bands C–O–C (1267 cmꢀ1) as well.
One can see (Table 3) that all the secondary amides 4–8 are very
poor extractants for metal cations. The low binding efficiency to-
ward alkaline and alkaline earth metals by p-tert-butyl thiaca-
lix[4]arene derivatives is related to the poor donor ability of the
substituted carbonyl group and strong hydrogen bonding between
the protons of NH groups and carbonyl fragments of the amide
groups, which compete with cations for the coordination sites near
oxygen atoms of the carbonyl and phenolic groups. The latter as-
sumption can be also confirmed by the absorption band of the
associated amide groups (3290–3320 s mꢀ1) observed in the IR
spectra of all the secondary amides.
Thus, the poor extraction ability of the amides 4–8 toward
these cations can be explained by the association of secondary
amide groups, which compete for coordination with the cation-
substrate.
1H NMR and IR spectra of the compounds partial cone-(7 and 8)
and cone-(7 and 8) are also similar to those of appropriate partial
cone-6 and cone-6 stereoisomers. Thus, the identity of the spectral
characteristics of the stereoisomers of tetradodecyl- and tetraoc-
tadecylamides 7 and 8 with those of tetraoctylamides makes it
possible to conclude that the interaction of the stereoisomers of
tetraethers 2 with n-dodecyl- and n-octadecylamine does not lead
to the changes in the macrocycle conformation. Summarizing the
results, nine new derivatives of thiacalix[4]arene were obtained
with high yields by one-stage synthesis from the stereoisomers of
the tetraethers of thiacalix[4]arene 2.
High values of the extraction percent of Fe3þ cation for all the
investigated receptors can be related to the lipophilic character of
the complex formed that promoted the effective extraction of the
iron(III) picrate with pure dichloromethane. The percentage of ex-
traction of all the investigated metal ions by secondary amides 1,3-
alternate-6, 8, and cone-8 (Table 3) strongly differs from those of
other thiacalix[4]arenes. The extraction efficiency increases in the
range 1,3-alternate-8<1,3-alternate-6<cone-8. Probably these re-
ceptors are also able to extract picric acid. This was examined for
conformational isomers of the p-tert-butyl thiacalix[4]arene 4–8
tetrasubstituted with phenyl, benzyl, octyl, dodecyl, and octadecyl
groups (Table 4).
2.2. Picrate extraction method, the percents of extraction,
extraction constants log Kex, and the complex stoichiometry
As shown, 1,3-alternates-6,8 and cone-8 are able to extract picric
acid from aqueous solution. The extraction efficiency changes in the
range 1,3-alternate-6<cone-8<1,3-alternate-8 in accordance with
the increase of the electron donation properties of substituents and
with the individual orientation of the binding site for each
stereoisomer.
The abilities of the p-tert-butyl thiacalix[4]arene tetrasub-
stituted with the secondary amide fragments in three conforma-
tions to molecular recognition of alkaline, alkaline earth metal ions,
and p and d elements were estimated using the picrate extraction
method. This method is widely used for the investigation of com-
plexion properties of the synthetic receptors toward metal cat-
ions46,51,52 and includes the determination of the degree of
extraction by host molecules from water into an organic phase.
Based on recent publications,34,55,56 non-covalent self-assembly
promoted by silver cations has received our attention. In the liter-
ature,48 the ability of thiacalix[4]arenes to form ensembles with
silver triflate was described. The problem was if the aggregates with
S–Ag–S bridging fragments are formed in the conditions of ex-
traction procedure.
The alkaline (Liþ, Naþ, Kþ, Csþ), alkaline earth (Mg2þ, Ca2þ, Ba2þ
)
metal cations, and p (Al3þ, Pb2þ) and d (Fe3þ, Co3þ, Ni2þ, Cu2þ, Agþ,
Cd2þ, Hg2þ) elements were chosen as guests because of their bio-
chemical significance and/or toxicity properties.53,54 The degree of
guest extraction by the p-tert-butyl thiacalix[4]arenes 4–8 func-
tionalized with secondary amide substituents as well as the ex-
traction constants and the stoichiometry of the silver cation–
calixarene complexes in organic phase were determined as
described below. The influence of lipophilic alkyl and aryl
substituents on the binding efficiency toward metal cations was
also investigated.
Table 4
Percent of extraction (%E) of picric acid by thiacalix[4]arene derivatives 4–8
4
5
6
7
8
cone
partial cone
1,3-alternate
5
5
10
5
6
6
3
6
18
6
6
6
38
8
91
Extraction condition: [L]org.,init¼2.5ꢂ10ꢀ3 M, [MPic]aq,init.¼2.32ꢂ10ꢀ4 M.46

I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
7117
The extraction constants and the stoichiometry of the com-
(a)
Size Distribution by Intensity
6
5
4
3
2
1
0
plexes consisting of the silver cation and p-tert-butyl thiacalix[4]-
arenes functionalized with phenyl-4 and benzyl-5 groups at the
lower rim in cone, partial cone, and 1,3-alternate conformations
were investigated by picrate extraction method. As shown, the
stoichiometry of complexation for all the receptors does not de-
pend on their configuration and was approximately equal to 1:1.
The log Kex values varied from 3.2 to 4.2. This corresponds rather
well with the assumption of aggregate formation with S–Ag–S
bridges. The most effective configuration of amides 4 and 6 is 1,3-
alternate and is less for cone and partial cone. The extraction effi-
ciency for macrocycles-5 with benzylamide groups decreases in the
opposite direction: cone, partial cone>1,3-alternate (Table 5).
The stoichiometry and low extraction constants confirm the
assumption that the formation of intra- and intermolecular hy-
drogen bonding between the amide groups prevents donor ability
of the substituted carbonyl groups and the complexes exist with
alternating p-tert-butyl thiacalix[4]arene molecules and silver cat-
ions. One of the possible alternatives29,30,35 is the system consisting
of dimeric associates57 that are held together by a seam of hydrogen
bonds and silver cations.
0.1
1
10
100
1000
10000
Size (d.nm)
(b)
Size Distribution by Intensity
14
12
10
8
6
4
2
0
0.1
1
10
100
1000
10000
2.3. Dynamic light scattering
Size (d.nm)
Figure 3. The systems consisting of benzyl-5 in partial cone conformation and silver
cations are submitted: (a) through 3 h and (b) through 28 h.
In accordance with the assumptions proposed, the ability of the
systems to self-associate and aggregate with silver cations in the
organic phase was examined by dynamic light scattering29,34,58
using the same conditions as picrate extraction. Silver nitrate was
used as a substrate and the measurements were carried out 3 h
after the solution preparation at 20 ꢁC. The kinetic stability of the
systems was proven in repeated measurements under similar
conditions after 28 h.
All the p-tert-butyl thiacalix[4]arene derivatives with secondary
amide fragments except benzyl-5 (1,3-alternate) and dodecyl-7
(partial cone) are able to form dimeric associates of about 1.1–
2.7 nm (Table 6). Also, aggregates with a hydrodynamic diameter of
more than 1200 nm were observed for the same systems as in the
case of peptide molecules.59 While the self-associates of about 1.1–
2.7 nm are counted in different time intervals, the equilibrium is
shifted toward dimer accumulation followed by the increase of the
dispersion intensity of these particles. Thus, the dispersion in-
tensity (%) of the systems consisting of p-tert-butyl thiacalix[4]ar-
enes functionalized with phenylamide fragments in partial cone
and 1,3-alternate conformations changed during 28 h from 37% to
89% and from 72% up to 86%, respectively. Conversely, the part of
aggregates with the size of more than 1200 nm and polydispersity
index decreased in accordance with predominant formation of the
dimers in the system stabilization processes. A similar tendency
was observed for the systems consisting of p-tert-butyl thiaca-
lix[4]arene derivatives and silver cations, the equilibrium shifted to
the preferable formation of the aggregates of about 70–170 nm
(Fig. 3).
Table 5
Percent extraction (%E), extraction constants log Kex, and stoichiometry complexes
of 4–6 with silver cation forming in the organic phase
Percent
Stoichiometry
log Kex
cone-4
29
10
29
29
26
35
44
51
60
0.9
0.8
1.0
1.2
0.9
0.8
0.8
0.8
0.8
3.3
3.2
4.0
4.2
4.1
3.6
3.6
3.6
4.1
partial cone-4
1,3-alternate-4
cone-5
partial cone-5
1,3-alternate-5
cone-6
partial cone-6
1,3-alternate-6
Extraction condition: [L]org.,init¼10ꢀ4–2.5ꢂ10ꢀ3 M, [MPic]aq,init.¼2.32ꢂ10ꢀ4 M.46
Table 6
The size of the particles in the system consisting of thiacalix[4]arene derivatives 4–8 in CH2Cl2 (HPLC), nm, polydispersity index
Peak mean 1 int, d nm/Peak area 1 int, % Peak mean 2 int, d nm/Peak area 2 int, % Peak mean 3 int, d nm/Peak area 3 int, %3
PDI
3 h
3 h
28 h
3 h
28 h
3 h
28 h
28 h
cone-4
1.9/67.8
2.7/88.6
2.5/86.0
2.0/26.0
2.7/80.5
1500/32.2
2514/11.4
2786/14.0
0.595
0.201
0.225
0.738
0.339
partial cone-4
1,3-alternate-4
cone-5
partial cone-5
1,3-alternate-5
cone-6
partial cone-6
1,3-alternate-6
cone-7
1.0/37.0
1.9/72.5
1.2/19.7
4376/63.0
1256/27.5
0.822
0.449
0.416
119.0/80.3
296.2/74.0
270.3/84.6
1903/19.5
0.8/40.9
2.2/73.1
4897/59.1
2726/26.9
1.000
0.512
2.1/13.2
2.0/68.4
4010/2.1
0.540
0.578
1006/31.6
partial cone-7
1,3-alternate-7
cone-8
partial cone-8
1,3-alternate-8
1.3/7.7
1.1/12.5
1.8/55.5
303.0/85.0
115.0/88.3
4144/6.5
5093/87.5
3660/44.5
0.421
1.000
1.000
2.2/11.7
2.7/67.6
0.429
0.674
2180/37.4

7118
I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
Table 7
The size of the particles in the system consisting of thiacalix[4]arenes derivatives 4–8 and silver cation in CH2Cl2 (HPLC), nm, polydispersity index
Peak mean 1 int, d nm/Peak area 1 int, % Peak mean 2 int, d nm/Peak area 2 int, % Peak mean 3 int, d nm/Peak area 3 int, %
PDI
3 h
3 h
28 h
3 h
28 h
3 h
28 h
28 h
cone-4
1.5/6.1
124.7/81.6
124.7/100
70.8/69.9
120.2/100
153.2/100
153.7/98.6
169.5/97.6
150.4/93.7
88.4/40.5
340.1/60.2
120.6/91.8
22.4/8.2
5016/9.1
0.211
0.187
0.287
0.150
0.189
0.247
0.229
0.241
0.339
partial cone-4
1,3-alternate-4
cone-5
partial cone-5
1,3-alternate-5
cone-6
1.6/39.9
215.3/60.1
0.894
1.000
0.241
0.591
0.391
0.417
0.211
0.703
1.4/21.7
4450/100
4243/8.4
1.3/2.7
70.4/97.3
117.8/76.0
145.7/83.3
69.4/74.0
134.0/83.7
191.0/46.9
1.5/20.5
0.8/10.2
1.6/26.0
1.7/8.9
3346/3.53
4250/6.4
5277/1.4
5113.3/2.4
5150/2.7
partial cone-6
1,3-alternate-6
3985/6.1
3555/11.3
1.6/41.5
cone-7
2.1/35.6
224.2/44.2
2682/20.2
0.547
0.136
partial cone-7
1,3-alternate-7
cone-8
partial cone-8
1,3-alternate-8
3.1/57.9
1.9/1.2
2.8/52.7
3.5/38.2
2.2/18.6
121.2/97.9
149.5/95.0
92.0/84.1
91.2/99.6
139.0/99.2
2743/42.1
3490/3.6
3967/28.2
4775/2.1
4470/5.0
5025/5.9
5290/0.4
5560/1.7
0.493
0.488
0.517
0.825
0.583
0.213
0.292
0.109
0.133
0.190
167.0/96.0
33.6/19.1
635.0/62
152.0/59.8
2.9/7.50
3912/19.3
The formation of nanoscale particles with hydrodynamic di-
ameter of about 70–170 nm, (Table 7) after the addition of silver
ions confirms again the aggregation via S–Ag–S bridges. The de-
crease in the part of the particles of about 1.1–2.7 nm may be due to
the aggregation of preliminary formed dimers into the associated
structures of about 70–170 nm by a seam of hydrogen bonds and
silver cations.
For systems 7 and 8, the hydrodynamic size of nanoscale par-
ticles tends to increase in the order cone, partial cone, 1,3-alternate.
It is interesting that the hydrodynamic diameter of the particles
containing silver cations and amides 4 and 6 are changed in the
opposite direction: 1,3-alternate<cone, partial cone. These results
coincide well with picrate extraction characteristics, i.e., increase of
log Kex value is accompanied by the decrease in the hydrodynamic
size of particles (see Table 7 for benzyl-5 derivatives in cone, partial
cone, and 1,3-alternate conformations).
mixture was refluxed for 1.5 h, excess of SOCl2 was removed; re-
mainder was dried under reduced pressure for 2 h. The solution of
amine (aniline, benzylamine, octylamine) (33.6ꢂ10ꢀ3 mol) and
triethylamine (5 mL, 0.04 mol) in 50 mL of methylene chloride was
added. The mixture was stirred at room temperature overnight. The
reaction was quenched by addition of 2 M HCl (30 mL). The organic
layer was separated, dried (mol. sieves, 3 Å) and evaporated in
vacuo. The residue was crystallized from the ethanol/methylene
chloride.
4.1.1. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-
tetrakis[(phenylamidocarbonyl)-methoxy]-2,8,14,20-
tetrathiacalix[4]arene (cone-4a)
Yield: 1.18 g (90%). Mp: 226 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
9.41 (s, 4H, NH), 7.57–7.55 (m, 8H, ArH), 7.39 (s, 8H, ArH), 7.19–7.14
(m, 8H, ArH), 7.04–6.99 (m, 4H, ArH), 4.98 (s, 8H, OCH2CO), 1.14 (s,
36H, (CH3)3C). 13C NMR (75 MHz, CDCl3)
166.5, 157.6, 147.7, 137.1,
d
135.0, 128.8, 127.9, 124.6, 120.4, 74.9, 34.3, 31.1. IR (KBr) nmax 1265,
1683, 2870, 2962, 3301. MS (ESI): calcd for [M+Na]+ m/z¼1275.4,
found m/z¼1275.6. El. Anal. Calcd for C72H76N4O8S4: C, 68.98; H,
6.11; N, 4.47; S, 10.23. Found: C, 68.91; H, 6.01; N, 4.44; S, 10.48.
3. Conclusion
Thus, new p-tert-butyl thiacalix[4]arenes functionalized with
secondary amide groups at the lower rim in cone, partial cone, and
1,3-alternate conformations were synthesized and their receptor
properties for metal ions of s (Liþ, Naþ, Kþ, Csþ, Mg2þ, Ca2þ, Ba2þ), p
(Al3þ, Pb2þ) and d (Fe3þ, Co3þ, Ni2þ, Cu2þ, Agþ, Cd2þ, Hg2þ) ele-
ments were studied using the picrate extraction method and dy-
namic light scattering (DLS). As was established, the
thiacalix[4]arenes investigated are poor extractants for all the
metal ions. Meanwhile they self-associate to form dimers of similar
size (1.1–2.7 nm) and nanoscale particles consisting of p-tert-butyl
thiacalix[4]arenes and silver cations with hydrodynamic diameters
of 70–170 nm. It was shown, that the size of the particles consisting
of silver cations and dimeric blocks of p-tert-butyl thiacalix[4]ar-
enes tetrasubstituted at the lower rim depends on the nature of the
secondary amide fragment and the conformation of the receptor
molecule. The study of the ability of similar receptor structures to
form nanoscale aggregates with metal cations in organic phase has
recently received increasing attention.
4.1.2. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-
tetrakis[(phenylamidocarbonyl)-methoxy]-2,8,14,20-
tetrathiacalix[4]arene (partial cone-4b)
Yield: 1.18 g (90%). Mp: 277 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
9.52 (s, 1H, NH), 9.21 (s, 2H, NH), 8.15 (s, 1H, NH), 7.82 (s, 2H, ArH),
7.71 (s, 2H, ArH), 7.64–7.61 (m, 4H, ArH), 7.53–7.06 (m, 20H, ArH),
4.91 (d, J¼15.4 Hz, 4H, OCH2CO), 4.73 (d, J¼15.4 Hz, 4H, OCH2CO),
4.72 (s, 2H, OCH2CO), 4.61 (s, 2H, OCH2CO), 1.39 (s, 9H, (CH3)3C),
0.94 (s, 9H, (CH3)3C), 0.89 (s, 18H, (CH3)3C). 13C NMR (75 MHz,
CDCl3)
d 166.1, 165.5, 157.2, 149.0, 148.6, 148.0, 137.2, 137.0, 136.8,
136.7,135.8,132.8,132.2,129.0,128.8,127.9, 127.3,127.1,126.3,125.1,
124.5, 124.4, 120.5, 120.0, 119.4, 73.9, 34.2, 31.3, 30.7. IR (KBr) nmax
1260, 1694, 2870, 2906, 2961, 3295. MS (ESI): calcd for [M+Na]+
m/z¼1275.4, found m/z¼1275.5. El. Anal. calcd for C72H76N4O8S4: C,
68.98; H, 6.11; N, 4.47; S, 10.23. Found: C, 68.53; H, 6.07; N, 4.27; S,
10.31.
4. Experimental
4.1.3. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-
tetrakis[(phenylamidocarbonyl)-methoxy]-2,8,14,20-
tetrathiacalix[4]arene (1,3-alternate-4c)
4.1. General procedure of the synthesis of compounds
4(a–c), 5(a–c), and 6(a–c)
Yield: 1.17 g (89%). Mp: 266 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
8.51 (s, 4H, NH), 7.48–7.42 (m, 16H, ArH), 7.36 (m, 8H, ArH), 7.14
(m, 4H, ArH), 4.88 (s, 8H, OCH2CO), 0.69 (s, 36H, (CH3)3C). 13C NMR
(75 MHz, CDCl3) 166.1, 156.5, 149.4, 137.5, 131.0, 129.5, 127.2, 125.3,
Compounds 3(a–c) (1 g, 1.05ꢂ10ꢀ3 mol) were placed into
a round-bottom flask and SOCl2 (10 mL, 0.084 mol) was added. The
d

I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
7119
119.9, 70.6, 34.5, 30.6. IR (KBr) nmax 1255, 1693, 2871, 2906,
2960, 3288, 3393. MS (ESI): calcd for [M+Na]+ m/z¼1275.4, found
m/z¼1275.6. El. Anal. Calcd for C72H76N4O8S4: C, 68.98; H, 6.11; N,
4.47; S, 10.23. Found: C, 68.25; H, 6.10; N, 4.34; S, 10.92.
(s, 2H, ArH), 7.62 (s, 2H, ArH), 7.49 (d, J¼2.4 Hz, 2H, ArH), 7.15 (t,
J¼6.5 Hz, 1H, NH), 7.05 (d, J¼2.4 Hz, 2H, ArH), 4.99 (s, 2H, OCH2CO),
4.89 (d, J¼14.5 Hz, 2H, OCH2CO), 4.38 (s, 2H, OCH2CO), 4.37 (d,
J¼14.5 Hz, 2H, OCH2CO), 3.55–3.24, 3.16–3.08 (m, 8H,
HNCH2(CH2)6CH3), 2.61–2.52, 1.73–1.60, 1.21–1.14 (m, 48H,
HNCH2(CH2)6CH3), 1.34 (s, 9H, (CH3)3C), 1.31 (s, 9H, (CH3)3C), 1.03
(s, 18H, (CH3)3C), 0.90–0.81 (m, 12H, HN(CH2)7CH3). 13C NMR
4.1.4. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(benzylamido-
carbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene (cone-5a)
Yield: 1.29 g (94%). Mp: 227 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
(75 MHz, CDCl3)
d 168.5, 168.2, 167.8, 159.3, 158.1, 155.3, 147.4,
d
8.04 (t, J¼5.7 Hz, 4H, NH), 7.32 (s, 8H, ArH), 7.31–7.23 (m, 20H,
ArH), 4.79 (s, 8H, OCH2CO), 4.48 (d, J¼5.7 Hz, 8H, NCH2Ar), 1.09 (s,
36H, (CH3)3C). 13C NMR (75 MHz, CDCl3)
168.1, 147.5, 138.2, 134.8,
146.6, 146.4, 136.4, 135.1, 134.8, 133.4, 127.5, 127.3, 125.7, 125.6,
74.5, 73.8, 69.6, 39.5, 39.3, 39.0, 34.3, 34.2, 34.1, 31.8, 31.7, 31.7, 31.2,
31.1, 31.0, 29.7, 29.7, 29.4, 29.3, 29.2, 29.1, 27.15, 27.1, 26.7, 22.6,
22.5, 14.0. IR (KBr) nmax 1265, 1633, 2855, 2925, 2957, 3287. MS
(ESI): calcd for [MþNa]þ m/z¼1419.8, found m/z¼1419.9. El. Anal.
Calcd for C80H124N4O8S4: C, 68.73; H, 8.94; N, 4.01; S, 9.17. Found:
C, 68.45; H, 8.93; N, 3.96; S, 9.39.
d
128.5, 128.1, 127.9, 127.2, 74.4, 43.0, 34.1, 31.1. IR (KBr) nmax 1263,
1675, 2870, 2961, 3323. MS (ESI): calcd for [MþNa]þ m/z¼1331.5,
found m/z¼1331.7. El. Anal. Calcd for C76H84N4O8S4: C, 69.69; H,
6.46; N, 4.28; S, 9.79. Found: C, 69.30; H, 6.57; N, 4.27; S, 10.42.
4.1.5. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(benzyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(partial cone-5b)
4.1.9. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octylamido-
carbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(1,3-alternate-6c)
Yield: 1.26 g (92%). Mp: 216 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
Yield: 0.95 g (72%). Mp: 62 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
9.03 (t, J¼6.5 Hz, 1H, NH), 8.27 (t, J¼6.5 Hz, 2H, NH), 7.65 (s, 2H,
d
7.79 (t, J¼6.1 Hz, 4H, NH), 7.54 (s, 8H, ArH), 4.09 (s, 8H, OCH2CO),
ArH), 7.53 (s, 2H, ArH), 7.43–7.15 (m, 21H, ArH, NH), 6.97 (d, J¼2.4 Hz,
2H, ArH), 6.87–6.83 (m, 2H, ArH), 5.03 (s, 2H, OCH2CO), 4.85 (d,
J¼14.9 Hz, 2H, OCH2CO), 4.67 (dd, 2J¼14.5 Hz, 3J¼6.5 Hz, 2H,
NCH2Ar), 4.59 (d, J¼5.9 Hz, 2H, NCH2Ar), 4.43 (dd, 2H, 2J¼14.5 Hz,
3J¼6.5 Hz, NCH2Ar), 4.40 (s, 2H, OCH2O), 4.28 (d, J¼14.9 Hz, 2H,
OCH2CO), 4.16 (d, J¼5.9 Hz, 2H, NCH2Ar), 1.32 (s, 9H, (CH3)3C), 1.16 (s,
1.22 (s, 36H, (CH3)3C), 3.30–3.22 (m, 8H, HNCH2(CH2)6CH3), 1.66–
1.58, 1.37–1.23 (m, 48H, HNCH2(CH2)6CH3), 0.88 (t, J¼6.4 Hz, 12H,
HN(CH2)7CH3). 13C NMR (75 MHz, CDCl3)
d 167.9, 156.7, 147.2, 133.3,
127.0, 71.0, 39.4, 34.2, 31.7, 30.0, 29.5, 29.1, 27.1, 22.5, 14.0. IR (KBr)
nmax 1264, 1654, 2854, 2925, 2956, 3320, 3419. MS (ESI): calcd for
[MþNa]þ m/z¼1419.8, found m/z¼1420.0. El. Anal. Calcd for
9H, (CH3)3C), 0.95 (s,18H, (CH3)3C). 13C NMR (75 MHz, CDCl3)
d
168.4,
C80H124N4O8S4: C, 68.73; H, 8.94; N, 4.01; S, 9.17. Found: C, 68.68; H,
167.9, 159.2, 158.0, 147.4, 146.7, 146.4, 138.3, 137.7, 136.3, 135.0, 134.7,
133.3, 128.7, 128.5, 128.4, 128.1, 127.9, 127.8, 127.6, 127.4, 127.3, 125.7,
125.5, 74.3, 73.7, 69.4, 43.1, 42.8, 31.3, 30.9. IR (KBr) nmax 1261, 1677,
2870, 2908, 2962, 3300. MS (ESI): calcd for [MþNa]þ m/z¼1331.5,
found m/z¼1331.6. El. Anal. Calcd for C76H84N4O8S4: C, 69.69; H, 6.46;
N, 4.28; S, 9.79. Found: C, 70.00; H, 6.53; N, 4.12; S, 10.32.
9.04; N, 3.95; S, 9.12.
4.2. General procedure of the synthesis of compounds 6(a–c),
7(a–c) and 8(a–c)
Compounds 2(a–c) (1 g, 0.9ꢂ10ꢀ3 mol) and ammonium chloride
(0.01 g, 0.2ꢂ10ꢀ3 mol) were placed into a round-bottom flask and
the amine (n-octylamine, n-dodecylamine, n-octadecylamine)
(1.8ꢂ10ꢀ2 mol) was added and mixed at 150 ꢁC for 2 h. Then the
reaction mixture was cooled to room temperature, ethanol
(100 mL) was added, the residue was filtered and dried at lower
pressure.
4.1.6. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(benzyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(1,3-alternate-5c)
Yield: 1.24 g (90%). Mp: 230 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
8.22 (t, J¼5.7 Hz, 4H, NH), 7.44 (s, 8H, ArH), 7.33–7.28 (m, 20H,
ArH), 4.49 (d, 3JHH¼5.7 Hz, 8H, NCH2Ar), 4.11 (s, 8H, OCH2CO), 1.05
(s, 36H, (CH3)3C). 13C NMR (75 MHz, CDCl3)
d
168.5, 157.0, 147.8,
4.2.1. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octylamido-
carbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene (cone-6a)
Yield: 1.25 g (95%). Mp: 116 ꢁC.
138.3, 133.9, 129.9–127.4, 71.4, 43.5, 34.4, 31.2. IR (KBr) nmax 1262,
1660, 2870, 2960, 3312. MS (MALDI-TOF): calcd for [M]þ
m/z¼1309.8, found m/z¼1313.8. El. Anal. Calcd for C76H84N4O8S4: C,
69.69; H, 6.46; N, 4.28; S, 9.79. Found: C, 68.25; H, 6.41; N, 4.15; S,
9.85.
4.2.2. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octylamido-
carbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene (partial
cone-6b)
4.1.7. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octylamido-
carbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene (cone-6a)
Yield: 0.98 g (75%). Mp: 116 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
Yield: 1.13 g (86%). Mp: 158 ꢁC.
4.2.3. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octylamido-
carbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(1,3-alternate-6c)
d
7.76 (t, J¼4.6 Hz, 4H, NH), 7.33 (s, 8H, ArH), 4.80 (s, 8H, OCH2CO),
3.38–3.31 (m, 8H, HNCH2(CH2)6CH3), 1.66–1.50, 1.43–1.19 (m, 48H,
HNCH2(CH2)6CH3), 1.10 (s, 36H, (CH3)3C), 0.86 (t, J¼7.3 Hz, 12H,
Yield: 1.09 g (74%). Mp: 62 ꢁC.
HN(CH2)7CH3). 13C NMR (75 MHz, CDCl3)
d 167.9, 157.5, 147.5, 134.8,
127.9, 74.6, 39.5, 34.2, 32.4, 31.8, 31.1, 29.7, 29.3, 27.1, 22.7, 14.1. IR
(KBr) nmax 1263, 1677, 2959, 3305. MS (ESI): calcd for [MþNa]þ
m/z¼1419.8, found m/z¼1419.9. El. Anal. Calcd for C80H124N4O8S4:
C, 68.73; H, 8.94; N, 4.01; S, 9.17. Found: C, 68.65; H, 9.09; N, 4.15; S,
9.14.
4.2.4. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(dodecyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(cone-7a)
Yield: 1.41 g (92%). Mp: 100 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
7.73 (t, J¼6.0 Hz, 4H, NH), 7.34 (s, 8H, ArH), 4.81 (s, 8H, OCH2CO),
3.38–3.31 (m, 8H, HNCH2(CH2)10CH3), 1.63–1.53, 1.35–1.25 (m, 80H,
HNCH2(CH2)10CH3), 1.12 (s, 36H, (CH3)3C), 0.88 (t, J¼7.1 Hz, 12H,
4.1.8. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octylamido-
carbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene (partial
cone-6b)
HN(CH2)11CH3). 13C NMR (75 MHz, CDCl3)
d 167.8, 157.5, 147.3, 134.7,
127.9, 74.4, 39.4, 34.1, 31.7, 30.9, 29.6, 29.5, 29.1, 27.0, 22.5, 13.8. IR
(KBr) nmax 1264, 1678, 2959, 3304. MS (ESI): calcd for [M]þ
m/z¼1622.6, found m/z¼1622.0. El. Anal. Calcd for C96H156N4O8S4:
Yield: 1.01 g (76%). Mp: 158 ꢁC. 1H NMR (300 MHz, 373 K,
CDCl3)
d
8.64 (t, J¼6.2 Hz, 1H, NH), 7.98 (t, J¼5.5 Hz, 2H, NH), 7.78

7120
I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
C, 71.06; H, 9.69; N, 3.45; S, 7.90. Found: C, 71.10; H,10.07; N, 3.44; S,
8.22.
1656, 2852, 2921, 2957, 3326. MS (ESI): calcd for [M]þ
m/z¼1959.2, found m/z¼1959.6. El. Anal. Calcd for
120H204N4O8S4: C, 73.57; H, 10.50; N, 2.86; S, 6.55. Found: C,
73.27; H, 10.75; N, 2.76; S, 6.21.
C
4.2.5. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(dodecyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(partial cone-7b)
4.2.9. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octadecyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(1,3-alternate-8c)
Yield: 1.39 g (91%). Mp: 166 ꢁC. 1H NMR (300 MHz, 373 K,
CDCl3)
d
8.66 (t, J¼6.1 Hz, 1H, NH), 7.98 (t, J¼6.1 Hz, 2H, NH), 7.79
(s, 2H, ArH), 7.62 (s, 2H, ArH), 7.48 (d, J¼2.7 Hz, 2H, ArH), 7.11 (t,
J¼6.1 Hz, 1H, NH), 7.05 (d, J¼2.7 Hz, 2H, ArH), 4.99 (s, 2H, OCH2CO),
4.87 (d, J¼16.1 Hz, 2H, OCH2CO), 4.39 (c, 2H, OCH2CO), 4.36 (d,
J¼16.1 Hz, 2H, OCH2CO), 3.54–3.37, 3.34–3.21, 3.18–3.07 (m, 8H,
Yield: 1.49 g (81%). Mp: 66 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
7.78 (t, J¼4.9 Hz, 4H, NH), 7.54 (s, 8H, ArH), 4.08 (s, 8H, OCH2CO),
3.32–3.21 (m, 8H, HNCH2(CH2)16CH3),1.63–1.47,1.37–1.22 (m,128H,
HNCH2(CH2)16CH3), 1.21 (s, 36H, (CH3)3C), 0.87 (t, J¼7.4 Hz, 12H,
HNCH2(CH2)10CH3),
1.70–1.59,
1.28–1.19
(m,
80H,
HN(CH2)17CH3). 13C NMR (75 MHz, CDCl3)
d 167.9, 156.8, 147.3,
HNCH2(CH2)10CH3), 1.33 (s, 9H, (CH3)3C), 1.30 (s, 9H, (CH3)3C), 1.04
133.3, 127.1, 71.1, 39.5, 34.2, 31.8, 31.0, 29.6, 29.3, 27.1, 22.6, 14.0. IR
(KBr) nmax 1259, 1649, 2850, 2918, 3316, 3419. MS (ESI): calcd for
[M]þ m/z¼1959.2, found m/z¼1959.4. El. Anal. Calcd for
(s, 18H, (CH3)3C), 0.87 (t, J¼7.3 Hz, 12H, HN(CH2)11CH3). 13C NMR
(75 MHz, CDCl3)
d 168.5, 168.2, 167.8, 159.3, 158.0, 155.3, 147.4,
146.5, 146.4, 136.3, 135.1, 134.8, 133.3, 127.4, 127.2, 125.7, 125.5,
74.4, 73.8, 69.6, 39.5, 39.3, 38.9, 34.2, 34.1, 31.8, 31.2, 31.1, 30.9,
29.5, 29.3, 27.1, 26.6, 22.6, 14.0. IR (KBr) nmax 1264, 1678, 2959,
3304, 1255, 1654, 2854, 2925, 2956, 3320. MS (ESI): calcd for [M]þ
m/z¼1622.6, found m/z¼1622.8. El. Anal. Calcd for C96H156N4O8S4:
C, 71.06; H, 9.69; N, 3.45; S, 7.90. Found: C, 71.19; H, 9.07; N, 3.45;
S, 8.26.
C120H204N4O8S4: C, 73.57; H, 10.50; N, 2.86; S, 6.55. Found: C, 73.42;
H, 10.80; N, 2.74; S, 6.21.
4.3. Determination of extraction parameters
4.3.1. The degree of extraction
The alkali and alkaline earth metal picrates were prepared
by stepwise addition of 2.32ꢂ10ꢀ4 M aqueous picric acid solu-
tion to 0.1 M aqueous solution of metal hydroxide (LiOH, NaOH,
KOH, CsOH, Ba(OH)2, Ca(OH)2) until neutralization, which was
checked by pH control with a glass pH-electrode. Other picrates
4.2.6. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(dodecyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(1,3-alternate-7c)
Yield: 1.42 g (93%). Mp: 56 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
7.78 (t, J¼5.0 Hz, 4H, NH), 7.54 (s, 8H, ArH), 4.08 (s, 8H, OCH2CO),
were prepared by stepwise addition of
a
3.02ꢂ10ꢀ4 M of
3.34–3.19 (m, 8H, HNCH2(CH2)10CH3), 1.69–1.52, 1.39–1.24 (m, 80H,
HNCH2(CH2)10CH3), 1.22 (s, 36H, (CH3)3C), 0.88 (t, J¼7.2 Hz, 12H,
Mg(NO3)2, Al(NO3)3, Pb(NO3)2, Fe(NO3)3, Co(NO3)3, Ni(NO3)2,
Cu(NO3)2, AgNO3, Cd(NO3)2, Hg(NO3)2 to 2.32ꢂ10ꢀ4 M aqueous
picric acid solution; in this case, the solutions were weakly
acidic (pH 4). Distilled water was used for preparation of all
HN(CH2)11CH3). 13C NMR (75 MHz, CDCl3)
d 167.9, 156.8, 147.3,
133.3, 127.0, 71.1, 39.5, 34.2, 31.8, 31.0, 29.6, 29.3, 27.1, 22.6, 14.0. IR
(KBr) nmax 1260, 1649, 2851, 2920, 2956, 3310, 3418. MS (ESI): calcd
for [M]þ m/z¼1622.6, found m/z¼1623.0. El. Anal. Calcd for
aqueous
solutions.
Aqueous
picrate
solution
(3 mL,
2.32ꢂ10ꢀ4 M) and 3 mL of a 2.32ꢂ10ꢀ4 M solution of thiaca-
lix[4]arene derivatives in CH2Cl2 (chemically pure) were shaken
for 30 min at room temperature (22 ꢁC). The absorbance Ai of
the aqueous phase after extraction, and, that of the aqueous
phase before extraction, A0, were measured at the wavelength
of the maximum absorption of the picrate ion, lmax¼355 nm.
The percentage of the cation extracted was calculated as the
ratio 100ꢂ(A0ꢀAi)/A0.
C
96H156N4O8S4: C, 71.06; H, 9.69; N, 3.45; S, 7.90. Found: C, 70.15; H,
9.69; N, 3.34; S, 7.79.
4.2.7. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octadecyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene
(cone-8a)
Yield: 1.69 g (92%). Mp: 105 ꢁC. 1H NMR (300 MHz, 373 K, CDCl3)
d
7.74 (t, J¼4.9 Hz, 4H, NH), 7.34 (s, 8H, ArH), 4.80 (s, 8H, OCH2CO),
3.38–3.31 (m, 8H, HNCH2(CH2)16CH3), 1.67–1.55, 1.37–1.25 (m,
144H, HNCH2(CH2)16CH3), 1.11 (s, 36H, (CH3)3C), 0.87 (t, J¼7.4 Hz,
4.3.2. Extraction constants log Kex and stoichiometry of the
complexes
12H, HN(CH2)17CH3). 13C NMR (75 MHz, CDCl3)
d 168.0, 157.5, 147.4,
Extraction experiments were performed at various ligand con-
centrations (1ꢂ10ꢀ4–2.5ꢂ10ꢀ4). Silver picrate was prepared by
stepwise addition of a 1.6ꢂ10ꢀ2 M of AgNO3 to 2.32ꢂ10ꢀ4 M
aqueous picric acid solution; in this case, the solutions were weakly
acidic (pH 4). The log Kex and n values were determined from the
plot of log(a/1ꢀa) versus log[L]org. as described elsewhere.42
134.8, 128.0, 74.5, 39.5, 34.2, 31.8, 31.0, 29.6, 29.3, 27.1, 22.6, 14.0. IR
(KBr) nmax 1265, 1677, 2960, 3304. MS (ESI): calcd for [M]þ
m/z¼1959.2, found m/z¼1959.8. El. Anal. Calcd for C120H204N4O8S4:
C, 73.57; H, 10.50; N, 2.86; S, 6.55. Found: C, 73.82; H, 10.80; N, 2.85;
S, 6.21.
4.2.8. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(octadecyl-
amidocarbonyl)-methoxy]-2,8,14,20-tetrathiacalix[4]arene (partial
cone-8b)
4.4. Dynamic light scattering (DLS)
Yield: 1.76 g (96%). Mp: 135 ꢁC. 1H NMR (300 MHz, 373 K,
CDCl3)
d
8.63 (t, J¼5.1 Hz, 1H, NH), 7.91 (t, J¼5.1 Hz, 2H, NH), 7.79
The particle sizes were determined by Zetasizer Nano ZS in-
strument at 20 ꢁC. The instrument contains a 4 mW He–Ne laser
operating at a wavelength of 633 nm and incorporates non-invasive
backscatter optics (NIBS). The measurements were performed at
the detection angle of 173ꢁ and the measurement position within
the quartz cuvette was automatically determined by the software.
The solutions of the systems investigated were prepared by addi-
tion of silver nitrate to 10 mL of 10ꢀ3 M solution of thiacalixarene
derivatives in CH2Cl2 (HPLC). The mixture was mechanically shaken
for 2 h and then magnetically stirred in thermostated water bath at
(s, 2H, ArH), 7.62 (s, 2H, ArH), 7.49 (d, J¼2.8 Hz, 2H, ArH), 7.11 (t,
J¼5.1 Hz, 1H, NH), 7.05 (d, J¼2.8 Hz, 2H, ArH), 4.99 (s, 2H,
OCH2CO), 4.86 (d, J¼14.5 Hz, 2H, OCH2CO), 4.39 (s, 2H, OCH2CO),
4.36 (d, J¼14.5 Hz, 2H, OCH2CO), 3.54–3.37, 3.34–3.23,
3.16–3.08 (m, 8H, HNCH2(CH2)10CH3), 2.56–0.85 (m, 156H,
HNCH2(CH2)16CH3). 13C NMR (75 MHz, CDCl3)
165.0, 159.3, 158.1, 155.4, 147.4, 146.6, 146.3, 136.3, 135.1, 134.8,
133.3, 127.9, 125.6, 74.5, 73.8, 69.7, 39.5, 39.4, 39.0, 34.2, 34.1, 31.9,
31.0, 29.6, 29.3, 28.3, 27.1, 26.7, 22.6, 14.0. IR (KBr) nmax 1253,
d 168.4, 168.2, 167.8,

I.I. Stoikov et al. / Tetrahedron 64 (2008) 7112–7121
7121
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Acknowledgements
The financial support from RFBR (06-03-32160), CRDF (RUC1-
2825-KA-06), joint program of CRDF and Ministry of Science and
Education of Russian Federation ‘Fundamental Researches and
Higher Education’ (REC-007) is gratefully acknowledged.
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Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.05.057.
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