The synthesis of tetracarbonyl derivatives of thiacalix[4]arene in different conformations and their complexation properties towards alkali metal ions

Article abstract of DOI:10.1016/S0040-4020(03)00077-2

The three conformations of 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis[(benzoyl)methoxy]-2,8,14, 20-tetrathiacalix[4]arene 1: cone, partial cone and 1,3-alternate, were prepared by the treatment of 5,11,17,23-tetra-tert-butyl-2,8,14,20-tetrathiacalix

Full text of DOI:10.1016/S0040-4020(03)00077-2

Tetrahedron 59 (2003) 1469–1476
The synthesis of tetracarbonyl derivatives of thiacalix[4]arene in
different conformations and their complexation properties
towards alkali metal ions
Ivan I. Stoikov,a Omran A. Omran,a Svetlana E. Solovieva,b Shamil K. Latypov,b
b
Konstantin M. Enikeev,b Aidar T. Gubaidullin,b Igor S. Antipina and Alexander I. Konovalov
,
*
aKazan State University, Kremlevskaya str. 18, Kazan 420008, Russian Federation
bA.E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences Arbuzov str. 8, Kazan 420088, Russian Federation
Received 19 September 2002; revised 9 December 2002; accepted 9 January 2003
Abstract—The three conformations of 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis[(benzoyl)methoxy]-2,8,14,20-tetrathiacalix[4]arene
1: cone, partial cone and 1,3-alternate, were prepared by the treatment of 5,11,17,23-tetra-tert-butyl-2,8,14,20-tetrathiacalix[4]arene-
25,26,27,28-tetraol (TCA) with a-bromo acetophenone in the presence of appropriate alkali carbonate M2CO3 (M¼Na, K, Cs) as base
catalyst in acetonitrile. Structure of the conformers were established by 1H NMR, 1H–1H COSY, 1D NOE, 2D ROESY and X-ray
experiments. The alkali cation binding selectivity of the obtained macrocycles was investigated by the ion-pair extraction method. q 2003
Elsevier Science Ltd. All rights reserved.
1. Introduction
Calixarenes are one of the most important macrocyclic
molecules as hosts for binding neutral and charged
molecules.1–3 These compounds can be easily synthesized
from cheap and commercially available starting materials,
e.g. 4-tert-butylphenol and formaldehyde. Because of the
many possibilities for modification of the upper and/or the
lower rims a wide variety for calixarenes has been
prepared.4,5 Replacement of the original methylene bridges
between the aromatic units in calixarenes by sulfur atoms
has been reported recently, leading to thiacalix[4]arenes
(TCA).6–8 Thiacalix[4]arenes were found to bind transition
metal ions very well without the introduction of supplemen-
tary ligating groups at the lower or upper rims owing to the
coordination of the bridging sulfur atom with metal
ions.9–11
2. Results and discussion
As a part of our efforts to understand ‘structure—ion
recognition’ relationships, we report herein the stereoselective
Although TCA exists in the cone conformation the complete
O-alkylation of the OH groups of TCA can theoretically
lead to the formation of four possible conformational
isomers: cone, partial cone, 1,2- and 1,3-alternates.
Nevertheless, direct alkylation by alkyl halogenides in
acetone or acetonitrile gives the 1,3-alternate conformer as
isolated product irrespective of the nature of the base
catalyst.15
synthesis of three conformations of 5,11,17,23-tetra-tert-
butyl-25,26,27,28-tetrakis[(benzoyl) methoxy]-2,8,14,20-tet-
rathiacalix[4]arene 1 and comparison of alkali cation binding
ability of three conformational isomers of 1 and 5,11,17,23-
tetra-tert-butyl-25,26,27,28-tetrakis[(ethoxycarbonyl)-
methoxy]-2,8,14,20-tetrathiacalix[4]arene 2.12–14
Keywords: thiacalix[4]arenes; synthesis; conformations; extraction.
*
Corresponding author. Tel.: þ7-8432-315463; fax: þ7-8432-752253;
e-mail: igor.antipin@ksu.ru
Reagents containing electrononegative groups such as
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00077-2

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I. I. Stoikov et al. / Tetrahedron 59 (2003) 1469–1476
ethoxycarbonyl are capable of coordination with metal
cations and allow stereoselective alkylation due to cation
template effect. Miyano et al.12 have developed the template
approach to lower rim alkylation of TCA by ethyl
bromoacetate. This was based on the application of different
alkali carbonate M2CO3 (M¼Na, K, Cs) as base catalyst in
acetone at the reflux or DMF at 608C. Reaction of TCA with
ethyl bromoacetate in the presence of Na2CO3, K2CO3,
Cs2CO3 gave the cone, partial cone and 1,3-alternate of
tetra-O-alkylation product 2 in good yields ranging from 58
to 78% (after column chromatography). Later, Hosseini
et al.13 and Stibor et al.14 investigated this reaction and the
structure of the products in detail.
reflux during 2 days. However, the presented 1H NMR
spectrum does not completely correspond to the 1,3-
alternate structure. The multiplets at 0.95–1.35 and 7.85–
7.90 ppm were assigned to But and calixarene aromatic
protons, respectively. Theoretically, in the 1H NMR
spectrum of symmetrical structures like 1,3-alt-1 these
protons should appear as singlets, but never as multiplets.
Moreover, according to our results (vide infra) the multiplet
at 7.85–7.90 ppm corresponds to the ortho-hydrogen atom
of phenyl substituents at lower rim. The multiplicity of But
signals can indicate the formation of a mixture of isomers
with the predominance of 1,3-alt-1.
2.1. Structure analysis by NMR spectroscopy
a-Bromoacetophenone is a less active electrophilic reagent
than ethyl bromoacetate, therefore, harsher conditions for
the alkylation reaction are needed. It was found that tetra-O-
alkylation of TCA in acetonitrile at reflux allows high yields
and stereoselectivity to be achieved. The treatment of TCA
with a-bromoacetophenone in the presence of an alkali
carbonate gives three conformational isomers out of the
possible four, i.e. cone, partial cone and 1,3-alternate, as
assigned by one- and two-dimensional NMR experiments
(vide infra). No evidence of 1,2-alternate product formation
in the reaction mixture was found. This might be attributed
to the lowest thermodynamic stability of this conformer in
the case of tetra-substituted derivatives of thiacalix[4]arenes.
The selective formation of 1,2-alternate product was estab-
lished for thiacalix[4]arenes, containing two bridge frag-
ments at the lower rim.16,17
The absence of methylene bridges, the proton signals of
which are used for conformational structure assignment of
normal calix[4]arenes, makes the determination of the
conformation of thiacalix[4]arene derivatives difficult. So,
the chemical shifts and resonance patterns of other protons
as well as 2D NMR experiments (COSY, ROESY) were
used to establish the structure of the obtained macrocycles.
In the unsymmetrical structure of paco-1, there are three
non-equivalent tert-butyl groups which should give a 2:1:1
ratio of resonance patterns in the proton spectrum (Fig. 2).
On this basis the isomer having But peaks at 1.13 (18H, s),
1.32 (9H, s) and 1.37 (9H, s) was defined as partial cone.
Analysis of the splitting pattern of the calixarene aromatic
protons and methylene groups of lower rim substituents
confirm the partial cone structure as well. Each group of
these protons appeared as two doublets and two singlets.
This is in agreement with both theoretical calculations and
experimental observations for similar compounds.12,14
Aromatic shielding effect analysis is also in line with this
conclusion.
As in the case of the TCA reaction with ethyl bromoacetate,
the alkali metal carbonates demonstrate a distinct influence
on the conformational structure (Fig. 1) of the products
obtained. Base catalyst Na2CO3 gave selectively cone
conformer in the isolated yield of 68%. The fractional
crystallization from chloroform–acetonitrile mixture was
used for product separation instead of column chromato-
graphy.12 Also paco-1 was successfully isolated from the
reaction mixture in 7% yield. The reaction in the presence of
K2CO3 affords the only product, paco-1, in an isolated yield
of 75%. Using Cs2CO3 as base catalyst led to the formation
of 1,3-alt-1 with 40% yield. It was easily separated from
other products because it was practically insoluble in cold
acetonitrile. Fractional crystallization from chloroform–
acetonitrile mixture allowed the isolation of distal disub-
stituted derivatives 3 and paco-1 in 15 and 7%, respectively.
All the protons of phenyl rings of the calixarene 1 platform
are equivalent in the cone and 1,3-alternate conformations
1
that is why their H NMR spectra are very simple and
similar: But (36H, s), –OCH2CO– (8H, s), Ar-H (8H, s),
m-Ph-H (8H, m), p-Ph-H (4H, m), o-Ph-H (8H, d) (see
Section 4). Nevertheless, conformational assignment may
be carried out by the comparison of methylene protons
chemical shifts of –OCH2CO– moieties. In 1,3-alt-1, these
protons are in the shielding field of two adjacent phenyl
groups so they should resonate at a higher field than those of
the cone conformer. Thus, the isomers which exhibited CH2
protons at 6.09 and 5.33 ppm were assigned to cone-1 and
1,3-alt-1, respectively. Unlike cone-2 and 1,3-alt-2, the
peaks corresponding to But and calixarene aromatic protons
Recently, the synthesis of 1,3-alt-1 with very low yield
(15%) was reported18 by the reaction of TCA with a-
chloroacetophenone in the presence of NaI in acetone at
Figure 1. Four possible conformers of 1.

I. I. Stoikov et al. / Tetrahedron 59 (2003) 1469–1476
1471
Figure 2. 1H NMR spectrum of paco-1.
are not significantly distinguished for both isomers of 1 and
cannot be used for the structure identification of the
macrocycles.
only with ArH (7.37 ppm) but also with the ortho-phenyl
protons (o-PhH, 7.91 ppm) and –OCH2CO– groups
(5.31 ppm). Moreover, there are cross peaks between the
–OCH2CO– (5.31 ppm) groups and o-PhH (7.91 ppm) and
ArH (7.37 ppm) (Fig. 3b). The interactions mentioned
above are only possible for the 1,3-alternate conformation.
The additional confirmation of this assignment was obtained
from 2D ROESY experiments. These experiments were
used to evaluate inter proton proximity because only closely
situated protons give rise to the cross peaks in the 2D
ROESY spectrum due to dipole-dipole interactions between
them. In the spectrum of cone-1 two strong interactions
were observed: i) between tert-butyl (1.12 ppm) and
aromatic protons of calixarene (ArH, 7.36 ppm), ii)
between –OCH2CO– groups (6.08 ppm) and ortho-phenyl
protons of narrow rim substituents (o-PhH, 7.96 ppm) (Fig.
3a). The spectrum of 1,3-alt-1 contains additional cross
peaks. Namely, the tert-butyl group (1.13 ppm) interacts not
2.2. Alkali metal ions extraction
To evaluate the ability of the thiacalixarene derivatives 1 to
recognize alkali metal ions, a liquid–liquid extraction (in
mutually saturated water-dichloromethane system) of their
picrate salts has been carried out and the extraction
constants have also been determined. The extraction
equilibrium is described by Eq. (1), where Mþ, L, Pic2,
MLþ, and MLþn Pic2 denote the metal ion, ligand (here, 1),
picrate anion, metal complex and ion-pair, respectively,
while n is the number of ligands that react with one alkali
metal ion.
Mþaq þ nLorg þ Pic2aq X MLþn Pico2rg
The percentage extraction E% and extraction degree, a,
were calculated according to Eq. (2).
ð1Þ
E% ¼ a £ 100% ¼ ½MLþn Pic2ꢀorg=½Pic2ꢀaq;init £ 100% ð2Þ
The thermodynamic extraction constant, Kex, is given by
Eq. (3).
Figure 3. The important dipole–dipole interactions in cone-1 (a) and 1,3-
alt-1 (b).
n
Kex ¼ ½MLþn Pic2ꢀorg=½Mþꢀaq½Pic2ꢀaq½Lꢀorg
ð3Þ

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I. I. Stoikov et al. / Tetrahedron 59 (2003) 1469–1476
The rather unpredictable stoichiometry of 1:4 for paco-1
was only observed for the smallest alkali cation. It
indicates that three O–CH2–C(O)Ph groups cannot interact
cooperatively with small Liþ cation and each ligating
unit binds it separately. In the case of 1,3-alt-1 two pairs of
O–CH2–C(O)Ph fragments located on opposite sides of the
macrocycle can participate in the interaction with two
lithium cations according to simple structural considerations
and the extraction data obtained. For the same reasons, the
Liþ cation is incorporated into the cavity formed by eight
oxygen atoms at narrow rim of cone-1. As a result of
different interaction cooperativity the extraction constants
sharply decrease in the order of cone.1,3-alternate.paco.
Naturally, paco-1 conformer demonstrates the weakest
extraction ability because each Liþ interacts with only one
O–CH2–C(O)Ph fragment. Using an additive approach,
log Kex of 1,3-alternate should be double the paco value. It
is in good agreement with experimental data: 1.51 and 0.77,
correspondingly, and indicates the absence of steric
hindrance for the binding of both lithium cations in 1,3-
alternate-1 conformation. The estimated log Kex for cone-1
is 3.1 (0.77£4) and significantly larger than the experimen-
tal value (2.05). So, the cavity formed by eight oxygen
atoms at the narrow rim of the calixarene is too large to
interact effectively with such a cation.
Figure 4. Plot of log(a/12a) versus log[L]org for lithium picrate extraction
in mutually saturated water–dichloromethane solvent system by the three
conformers of 1.
To determine the stoichiometry coefficient n of the
complexes forming in the organic phase Eq. (3) was
converted into Eq. (4).
log Kex ¼ logða=1 2 aÞ 2 log½Mþꢀaq 2 n log½Lꢀorg
ð4Þ
The plot of log(a/12a) versus log[L]org presents a straight
line, slope of which equals to n. Hereafter, we will also use
the host–guest ratio or complex stoichiometry L:Mþ.
Extraction constants Kex are calculated using the intercept
values (b).
The increase of cation size leads to significant changes in
complex stoichiometry and extraction selectivity. Complex
stoichiometry of sodium, potassium and caesium cations
with paco-1 are practically equal to 1:1 (Fig. 5d). Unlike the
small Liþ, these cations are able to interact cooperatively
with three ligating groups located on the same side of
macrocycle plane. A slight increase of host: guest ratio
(1:1.3) in the case of Naþ can be explained by weak binding
of the cation by separately situated O–CH2–C(O)Ph
groups. This is not observed for softer Kþ and Csþ cations,
in good agreement with the concept of hard–soft acids and
bases.
b ¼ log Kex þ log½Mþꢀaq
ð5Þ
It was found that plots of log(a/12a) against log[L]org for
lithium, sodium, potassium and cesium in mutually
saturated water–dichloromethane solvent system were in
all cases linear, and, therefore, Eq. 4 is valid. A
representative example is presented in Figure 4 for lithium
picrate and Table 1 gives the values of log Kex and n.
Lithium picrate forms complexes in the organic phase with
different stoichiometries: 1:1, 1:2 and 1:4 for cone, 1,3-
alternate and partial cone of 1, correspondingly. Thus four,
two or one O–CH2–C(O)Ph fragments can participate in
the binding of Liþ. The possible structures of these
complexes are schematically presented in Figure 5a–c.
The stoichiometry of 1,3-alternate-1 complexes is either 1:2
or 1:1. Small Liþ and Naþ ions form 1:2 complexes. It
means that in this case both pairs of O–CH2–C(O)Ph
fragments interact irrespective of each other and structural
changes caused by ion complexation on one side of 1,3-alt-1
do not cause significant hindrance for binding on the other.
The situation sharply changed for larger alkali cations for
which 1:1 stoichiometry was observed. So, 1,3-alt-1 is
unable to bind a second cation like Kþ or Csþ. Such
behavior could be rationalized in term of a negative
allosteric effect21–24 induced by a change of the con-
former’s spatial structure. In order to bind the first cation the
molecular cleft formed by two ligating groups may expand
To the best of our knowledge these are the first examples of
the stoichiometry differing from 1:1 for complex of
calix[4]arene derivatives with alkali metal ions. Only a
1:1 host–guest ratio was established for cone, 1,3-alternate
1
and partial cone of 2 by H NMR titration and for cone of
5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis-[(etoxy-
carbonyl)methoxy]-calix[4]arene by the extraction
method.19,20
Table 1. Extraction constants log Kex and stoichiometry complexes of 1 forming in the organic phase
Liþ
Naþ
Kþ
Csþ
na
Log Kex
E%b
na
Log Kex
E%b
na
Log Kex
E%b
na
Log Kex
E%b
Cone-1
Partial cone-1
1,3-Alternate-1
0.86
0.23
0.44
2.05
0.77
1.51
12
10
19
0.67
0.78
0.59
3.50
2.95
2.22
85
46
33
0.71
1.06
1.00
2.77
4.61
5.45
46
88
99
0.70
0.93
0.92
1.87
3.32
4.33
10
44
76
a
Average error of n is ^0.08.
Extraction condition:12 [L(¼1 or 2)]org,init¼2.5£1023 M, [MOH]aq,init¼0.1 M, [HPic]aq,init¼2.5£1024 M.
b

I. I. Stoikov et al. / Tetrahedron 59 (2003) 1469–1476
1473
Figure 5. The possible structures of thiacalix[4]arene conformer complexes with Liþ and Csþ: (a) cone-Liþ, (b) 1,3-alt-Liþ, (c) paco-Liþ, (d) paco-Csþ,
(e) 1,3-alt-Csþ. Small ellipses denote 4-tert-butylphenyl fragments.
to achieve the ideal interatomic distance needed for
complexation of large alkali cations. As a result the other
two ligating groups on the opposite side of 1,3-alternate
become closer to each other and thus the binding of second
cation does not occur (Fig. 5e). The complex of cone-1 with
all cations studied slightly deviated from 1:1 stoichiometry.
This may suggest that aromatic cavity of cone conformer
can also participate in the binding of alkali metal cations.
and ethyl acetate were used as model compounds. Among
empirical scales of basicity the calorimetric scales of
Gutmann25 DN or DH S0bCl5 (donor number) and Maria
and Gal26 DH8BF3 were chosen. They characterize directly
the energy of donor–acceptor interactions and define as the
enthalpy change for the formation of the 1:1 adduct between
Lewis acid (antimony pentachloride or boron trifluoride)
and electron pair donor compound. The data summarized in
the review of IUPAC Commission on physical organic
chemistry devoted to the scales of solvent parameters25
indicate that ethoxycarbonyl group interacts more strongly
than the phenylcarbonyl one with both hard and soft Lewis
acids. DH8SbCl5 of acetophenone and ethyl acetate are equal
to 262.8 and 271.5 kJ/mol, respectively.27 The same
relative order of donicity was observed for hard Lewis
acids like BF3. The values of DH8BF3 for acetophenone and
ethyl acetate are 274.52 and 275.55 kJ/mol, respectively.27
Figure 6 shows the log Kex of conformers versus alkali
metal ions. Cone-1 demonstrates the highest ability to
extract for the Naþ ion compared to other alkali metal ions
using CH2Cl2 as the organic phase. By contrast, paco-1 and
1,3-alternate-1 extract larger metal cations such as Kþ more
effectively. A similar dependence was shown for the
conformers of 2. To compare the extractability of
conformers of 1 measured in the present work and 2
determined earlier by Miano et al.12 the E% values were
calculated for 1 under the same extraction condition. The
data obtained are summarized in Table 1. Their comparison
is presented on Figure 7. One can see that the conformers of
1 generally exhibited better E% and selectivity than those of
2. However, paco-1 and -2 are dramatically distinguished by
their extraction properties. While paco-2 shows a small E%
for all alkali metal ions, the derivative containing phenyl-
carbonyl groups exhibits high efficiency and selectivity with
a preference for potassium ion. Although the behavior of
cone and 1,3-alternate conformers of 1 and 2 is closely
similar to the extractability of 1 exceeds that of 2 for all
alkali metal ions. Thus, the replacement of the ethoxy group
by phenyl leads to an increase in the extraction efficiency of
thiacalix[4]arene derivatives.
Several factors may be considered to rationalize this effect.
These are: (i) donor ability of carbonyl groups, (ii)
macrocycle lipophilicity, (iii) steric requirements. For
quantitative estimation of the donor ability of investigated
ligating groups the Lewis basicity values of acetophenone
Figure 6. The extraction constants of the conformers (log Kex) of 1 versus
alkali metal ions.
Figure 7. The percent extraction (E%) by three conformers of 1 and 2,
determined at the same extraction conditions (see the footnote of Table 1).

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I. I. Stoikov et al. / Tetrahedron 59 (2003) 1469–1476
alternate conformation and preorganization of ion binding
centers in the both mentioned conformations of 1 is similar.
Additionally, the correlation (r 2¼0.997) between log Kex
values of paco and 1,3-alternate conformers of 1 was
observed for the investigated alkali metal ions with the
exception of the sodium ion.
log Kexð1; 3-alt-1Þ ¼ 1:04 log Kexðpaco-1Þ þ 0:76
ð6Þ
The deviation of sodium ion from the common dependence
(higher extractability of paco with respect to 1,3-alternate)
indicates that only in this case can the third carbonyl group
of paco-1 participate in the ion binding.
In most investigations of the ligand binding ability by
extraction method E% values are only measured and
discussed. This is only sufficient for correct analysis of
‘structure–property’ relationships if the stoichiometry is not
significantly changed within the host–guest complexes
studied. Data obtained for Liþ ion (Table 1) indicate clearly
that the extraction constants Kex and percent extraction E%
lead to different conclusions about the extractability order of
thiacalix[4]arene conformers. According to E% the order is
1,3-alternate.coneqpaco, whereas the thermodynamic
parameter Kex shows: cone.1,3-alternateqpaco. The
essential change in complex stoichiometry is the reason
for these contradictory regularities. In the case of the other
ions studied the conclusions made on the basis of either Kex
or E% are in agreement because complex stoichiometry
does not significantly change. Using the determined
thermodynamic values we can conclude that cone con-
former extracts small alkali ions Liþ and Naþ best, but 1,3-
alternate—Kþ and Csþ.
Figure 8. X-ray structure of paco-1. H atoms are omitted for clarity.
So, the increasing extractability of 1 with respect to 2 cannot
be ascribed to the change of donor ability of the ligating
group.
There is no doubt that the replacement of ethoxy groups by
phenyl groups increases the receptor’s lipophilicity. More-
over, the dependences of E% versus alkali metal ion for
cone and 1,3-alternate conformers (Fig. 7) closely repro-
duce each other although the extraction degree of all ions by
the conformers of 1 is greater than 2. This fact could be
considered as confirmation of the receptor lipophilicity
effect that should be constant for different conformers.
The influence of steric requirements clearly appears in the
case of the paco conformer. Significant differences of
percent extraction and selectivity indicate that the spatial
structures of paco-1 and paco-2 are quite different.
Obviously, the planar and large CH2–C(O)Ph moieties
make the cavity less flexible and more preorganized than in
the case of CH2 –C(O)OEt substituents. The ethoxy
substituents are smaller and more flexible. As result they
are not able to fix a definite spatial arrangement where
carbonyl groups project into the cavity. Indeed, X-ray
structure analysis of paco-213 as well as cone-212 indicates
that the (ethoxycarbonyl)methoxy groups seem to be rather
randomly arranged. Suitable monocrystals of paco-1 were
obtained from CH2Cl2–hexane mixture (1:9) and investi-
gated by X-ray diffraction. Paco-1 crystallized in a
monoclinic form, space group P21/n (Fig. 8). No solvent
molecules were present in the lattice.
It is interesting to note that the selectivity of alkali metal ion
extraction does not completely correspond to the template
effect observed in the synthesis of corresponding con-
formers. Sodium and caesium ions promote the formation of
cone and 1,3-alternate due to strong and selective host-
guest complexation with the corresponding conformer. So,
the thermodynamic stability of the forming complex is a
principal factor controlling the result of these reactions. In
the case of potassium ions both partial cone and 1,3-
alternate conformers bind this ion quite strongly. Although
1,3-alt-1 binds potassium ions more strongly than paco-1
the main product of the reaction in the presence of K2CO3 is
partial cone. This may be a result of kinetic control of the
reaction. According to general considerations28 the cone to
1,3-alternate interconversion occurs via preliminary for-
mation of the partial cone conformer due to the rotation of
one phenyl ring. This conformation is stabilized by strong
interaction with the potassium ion (log Kex¼4.61) and
further inversion of second phenyl group does not take
place. Thus, reaction terminates at the formation of paco-1.
In paco-1, the dihedral angles of the four aromatic rings
A–D with S main plane are 89.0(2), 82.5(2), 40.3(3) and
80.5(2), correspondingly. So, the opposite rings B and D are
practically parallel to each other. Moreover, PhC(O)CH2–
moieties attached to these rings make interplanar angles of
88.2(5) and 83.6(4) with them.
3. Conclusion
Unlike paco-213 the two opposite substituents at the narrow
rim of paco-1 have their double bonded oxygen atom
oriented endo whereas the third one directs out of
macrocycle molecular cavity. Thus, the carbonyl groups
form a spatial arrangement that looks like that in the 1,3-
Among four possible conformers, the cone, partial cone and
1,3-alternateconformersofthiacalix[4]arenetetra-substituted
at the narrow rim bearing four ketone groups have been
synthesized using the template effect of alkali metal
ions. Ionophoric properties of isolated and structurally

I. I. Stoikov et al. / Tetrahedron 59 (2003) 1469–1476
1475
characterized macrocycles were investigated by the ion-pair
extraction method.
OCH2CO), 5.48 (2H, d, J¼15.9 Hz, OCH2CO), 5.92 (2H, s,
OCH2CO), 7.19 (2H, d, J¼2.4 Hz, ArH), 7.53 (2H, d,
J¼2.4 Hz, ArH), 7.62 (2H, s, ArH), 7.86 (2H, s, ArH),
7.34–7.59 (12H, m, m- and p-PhH), 7.92 (4H, d J¼7.3 Hz,
o-PhH), 7.98 (2H, J¼8.2 Hz, o-PhH), 8.01 (2H, d, J¼
9.0 Hz, o-PhH). Found: C, 72.40%; H, 6.19%; S, 10.79%.
Calcd for C72H72O8S4: C, 72.45%; H, 6.08%; S, 10.74%.
Our results show that the stoichiometries of complexes
(ligand/ion ratio) forming in the organic phase range from
1:1 to 1:4 and depend on some factors: (i) the size
complementarity of ion and cavity formed by four ligating
moieties at the narrow rim; (ii) allosteric effect. Thermo-
dynamic extraction parameters (log Kex) demonstrate that
the cone conformer exhibits the highest extractability
towards the Naþ ion compared to other alkali metal ions,
whereas paco and 1,3-alternate conformers extract more
effectively the larger Kþ ion. The higher ability and
selectivity of conformers of 1 compared to those of 2 for
alkali metal extraction. These macrocycles therefore have
perspectives for application as ionophores in ion selective
sensors.
4.1.3. 1,3-Alternate-1. Colorless crystals, mp 228–2308C
n
max/cm21 (in KBr): 2967 (CH) and 1709 (CO); (400 MHz,
CDCl3) 1.15 (36H, s, But), 5.33 (8H, s, OCH2CO), 7.39 (8H, s,
ArH), 7.45(8H, m, m-PhH), 7.55(8H, m, m-PhH), 7.93(8H, d,
J¼7.4 Hz, o-PhH). Found: C, 72.32%; H, 6.27%; S, 10.86%.
Calcd for C72H72O8S4: C, 72.45%; H, 6.08%; S, 10.74%.
All isomers of compound 1 showed an intense (100%) peak
in the MALDI-TOF-MS spectrum at m/z 1193 (the
molecular mass spectra were recorded on FINNIGAN
DYNAMO mass spectrometer with 1,8,9-trihydroxyantra-
cene as a matrix).
4. Experimental
4.2. NMR Spectrometry
4.1. General procedure for the preparation of 5,11,17,23-
tetra-tert-butyl-25,26,27,28-tetrakis[(benzoyl)methoxy]-
2,8,14,20-tetrathiacalix[4]arene (1)
1H NMR spectra of samples in CDCl3 (4 mg in 0.5 ml) were
recorded in Bruker MSL 400 and WM 250 NMR
spectrometers. Chemical shifts (ppm) are internally refer-
Parent thiacalix[4]arene TCA (1 g, 1.4 mmol) was sus-
pended in dry acetonitrile (50 ml) containing anhydrous
M2CO3 (M¼Na, K or Cs) (8.3 mmol) and a-bromoaceto-
phenone (1.65 g, 8.3 mmol). The reaction mixture was
refluxed under nitrogen for 40 h. The reaction was
monitored by TLC. After cooling, the reaction mixture
was treated in different ways.
1
enced to the TMS signal (0 ppm) in all cases. 1D H NMR
spectra. Size 32 K, pulse length 2.8 ms (308), 16 acqui-
sitions. 2D COSY Spectra. Sequence: D1-90-t1-90-t2;
relaxation delay D1¼0.5 s; 908 pulse 8.5 ms. 2D ROESY
Spectrum. Sequence: D1-90t1-Spin lock -t2, d1¼3 S, spin
lock 0.8 s 908 pulse 28 ms; TPPI-mode, NS¼16, DS¼2,
T¼298 K, matrix 512£512.
In the case of Na2CO3 and K2CO3, the solution was
evaporated to dryness and the solid residue was extracted by
chloroform. After concentration of the chloroform solution
the addition of acetonitrile led to the fractional crystal-
lization of pure conformational isomers: Na2CO3: 1.12 g,
68% of cone-1 and 0.11 g, 7% of paco-1; K2CO3: 1.24 g,
75% of paco-1.
4.3. X-Ray structure determination
The X-ray diffraction data for crystal paco-1 were collected
on a CAD4 Enraf-Nonius automatic four-circle difracto-
meter (graphite monochromator, Cu Ka radiation
˚
(1.54184 A), v scan method, u#57.38). Twenty five
centered reflections gave a refined unit cell of dimensions
˚
a¼17.648(4), b¼22.243(4), c¼19.040(7) A, b¼108.80(2)8,
In the case of Cs2CO3 after filtration the solid residue and
filtrate were treated separately. The solid residue was
extracted by chloroform. The addition of acetonitrile to the
concentrated extract gave 1,3-alt-1 (0.66 g, 40%). To
remove unreacted a-bromoacetophenone the filtrate was
evaporated to dryness. The treatment of the obtained
viscous oil with acetonitrile gave solid disubstituted
derivative 3 (0.20 g, 15%). Paco-1 was isolated from the
filtrate (0.11 g, 7%).
3
V¼7075.2 A , Z¼4, r¼1.07 g cm23. A total of 6043
˚
reflections were measured, of which 3777 were unique
with I.3s. The stability of crystals and of experimental
conditions was checked every 2 h using three control
reflections, while the orientation was monitored every 200
reflections by centering two standards. No significant decay
was observed. Corrections for Lorentz and polarization
effects were applied. The structure was solved in the
uniquely assignable space group P21/n by direct methods
and difference Fourier syntheses using SIR program29 and
MolEN package.30 All non-hydrogen atoms were refined
anisotropically, H-atoms were located in DF maps and were
included into structure factor calculations with fixed
positional and thermal parameters. The final R values
were R¼0.057, Rv¼0.066 for 3777 unique reflections with
F 2$3s. All calculations were carried out on a DEC Alpha
Station 200 computer, all figures were made using the
program PLATON.31
4.1.1. Cone-1. Colorless crystals, mp 130–1318C nmax
,
cm21 (in KBr): 2968 (CH) and 1710 (CO); d (400 MHz,
CDCl3) 1.13 (36H, s, But), 6.09 (8H, s, OCH2CO), 7.35 (8H,
m, m-PhH), 7.37 (8H, s, ArH), 7.55 (4H, m, p-PhH), 7.97
(8H, d, J¼7.4 Hz, o-PhH). Found: C, 72.30%; H, 6.28%; S,
10.90%. Calcd for C72H72O8S4: C, 72.45%; H, 6.08%; S,
10.74%.
4.1.2. Partial cone-1. Colorless crystals, mp 217–2198C.
max, cm21 (in KBr): 2960 (CH) and 1708 (CO); (400 MHz,
n
CDCl3) 1.13 (18H, s, But), 1.32 (9H, s, But), 1.37 (9H, s,
Crystallographic data (excluding structure factors) for the
structure paco-1 in this paper have been deposited with the
But), 5.36 (2H, d, J¼15.9 Hz, OCH2CO), 5.43 (2H, s,

1476
I. I. Stoikov et al. / Tetrahedron 59 (2003) 1469–1476
Miyanari, S.; Miyashi, T.; Miyano, S. Tetrahedron 2000, 56,
1437–1443.
Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 183412. Copies of the data can
be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: þ44-1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk].
9. Iki, N.; Morohashi, N.; Narumi, F.; Miyano, S. Bull. Chem.
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4.4. Extraction study
The alkali picrates were prepared from aqueous solutions of
picric acid and metal hydroxides. Aqueous picrate solution
(4 ml, 2.27£1024 M) containing 0.1 M metal hydroxide and
4 ml of a 1.3£1021–2£1024 M solution of thiacalixarene
derivatives 1 in CH2Cl2 were shaken for 60 min at room
temperature (228C). The absorbances Ai and A0 of the
aqueous phases after and before extraction were measured at
355 nm. The percent extraction was calculated as ratio
100(A02Ai)/A0. Extraction experiments were performed at
the different ligand concentration. The log Kex and n values
were determined from the plot of log(a/12a) versus
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Acknowledgements
This work was supported by the RFBR (02-03-32934, 02-
03-32280), joint program of CRDF and the Russian
Ministry of Education ‘Basic Research and Higher Edu-
cation’ (REC-007) and the program of Russian Academy of
Science ‘Nanomaterials and Supramolecular Systems’.
20. Danil de Namor, A. F.; Goitia, M. T.; Casal, A. R.; Velarde,
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