Di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone conformations: synthesis and divalent metal ion extraction

Article abstract of DOI:10.1016/j.tet.2007.11.065

Two series of di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone conformations are synthesized. The ionizable groups are oxyacetic acid moieties and N-(X)sulfonyl oxyacetamide units with X=methyl, phenyl, 4-nitrophenyl, and trifluoromethyl

Full text of DOI:10.1016/j.tet.2007.11.065

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Tetrahedron 64 (2008) 1187e1196
www.elsevier.com/locate/tet
Di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone
conformations: synthesis and divalent metal ion extraction
y
*
Chuqiao Tu, Kazimierz Surowiec, Jerzy Gega , David W. Purkiss, Richard A. Bartsch
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
Received 1 October 2007; received in revised form 9 November 2007; accepted 20 November 2007
Available online 22 November 2007
Abstract
Two series of di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone conformations are synthesized. The ionizable groups are
oxyacetic acid moieties and N-(X)sulfonyl oxyacetamide units with X¼methyl, phenyl, 4-nitrophenyl, and trifluoromethyl, which ‘tunes’ their
acidity. For competitive solvent extraction of alkaline earth metal cations from aqueous solutions into chloroform, the new ligands with
N-(X)sulfonyl carbamoyl groups are efficient extractants with Ba2þ selectivity. On the other hand, the dicarboxylic acid analogues exhibit little
selectivity in extraction of alkaline earth metal cations. For single species extractions of Pb2þ, the ligands with both types of ionizable groups
show very good extractions abilities. In single species extractions of Hg2þ, the N-(X)sulfonyl carboxamide ligands are highly efficient, in
contrast to the dicarboxylic acid compounds. Influences of the ionizable group identity, the crown ether ring size, and the presence of upper-
rim p-tert-butyl groups on divalent metal ion extraction are explored.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Calixarenes; Crown ethers; Molecular recognition; Solvent extractions
1. Introduction
only minimal adjustment of the ligand conformation. Since
such adjustment is both enthalpically and entropically expen-
sive, this improvement furnishes much more effective and
selective metal ion separations.1,2
The development of the field of liquideliquid separations
has been paralleling the progress of coordination chemistry
from the use of simple ligands to pre-organized metal ion
receptors. The advent of macrocyclic receptors, i.e., crown
ethers and calixarenes, produced a second revolution in
liquideliquid separation of metal ions following the monoden-
tate and bidentate extractants, which revolutionized the chemi-
stry for metal ion separations from aqueous solutions, from
separatory funnels to the industrial scale.1 The macrocyclic
ligands select cations primarily by their sizes, and the most
stable complexes are formed with the closest match between
host cavity and cation size.2 Another important factor is pre-
organization of the host macrocyclic molecules. The binding
of a specific metal ion by a pre-organized ligand requires
Calix[4]crowns, macrobicyclic compounds that combine
calix[4]arene and polyether units, have been widely used as
hosts for selective metal ion recognition for more than two
decades, since the earliest example of this family, p-tert-butyl-
calix[4]arene-1,3-crown-6-ether, was reported in 1983.3 The
complexation studies of calix[4]arene-crowns have mainly
been focused on dialkylated 1,3-bridged calix[4]arene-crown
ethers, which were found to exhibit high binding affinity and
selectivity in alkali and alkaline earth metal cation extractions.4
In contrast, very little is known about the ligating ability of the
corresponding 1,2-bridged regioisomers, probably because they
are more difficult to synthesize. Known members in this cate-
gory are limited. In general, they exhibit poor binding ability
and little selectivity toward metal cations.5
* Corresponding author. Tel.: þ1 806 742 3069; fax: þ1 806 742 1289.
E-mail address: richard.bartsch@ttu.edu (R.A. Bartsch).
Calix[4]arenes with pendant proton-ionizable groups are
found to be much more efficient interfacial carriers for metal
cations than related unfunctionalized calix[4]arenes with
y
Present address: Department of Chemistry, Czestochowa University of
Technology, 42-200 Czestochowa, Poland.
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.065

1188
C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
phenolic groups on the lower rim.6 Recently, we have under-
taken the synthesis and evaluation of di-ionizable calix[4]-
arene-1,2-crown ether ligands as divalent metal ion extrac-
tants.7 Di-ionized calix[4]arene-1,2-crown-4 ethers in the
cone conformation were found to be efficient alkaline earth
metal cation extractants with extraordinarily high selectivity
a small-scale reaction, a 27% yield of diester 4 was obtained
when the reaction was performed at 80 ꢀC for 72 h. However,
separation and purification of the product were difficult since
there were many side products. When large-scale reactions
were employed, the average yield of diester 4 dropped to
10e15%.
Hydrolysis of calixcrown diesters 4 and 5 with 10%
Me4NOH in H2OeTHF (1:1) gave diacids 6 and 7, respectively,
in nearly quantitative yields. Calixcrown diacids 6 and 7
were converted into the corresponding di(acid chloride)s by
reaction with oxalyl chloride in benzene at reflux for 5 h.
Formation of the di(acid chloride) was verified by IR spectro-
scopy with the appearance of a strong carbonyl group absorp-
tions at around 1810 cmꢁ1 and the disappearance of the
carbonyl group absorptions at about 1750 cmꢁ1. The di(acid
chloride)s were reacted with the corresponding sulfonamide
anions in THF to afford di-ionizable calixcrowns 8e15 in
41e83% yields.
for Ba2þ 7c
.
Since the crown ether ring is too small to accom-
modate Ba2þ, we proposed the extraction complex shown in
Figure 1. In this complex, the large divalent metal ion is sand-
wiched between the four polyether ring oxygens on one side
and the two ionized groups on the other. In an extension of
that study, we have now prepared analogues with larger
crown-5 and crown-6 ether rings and evaluated their alkaline
earth metal cation extraction abilities. In addition, the efficacy
of these new ligands as Hg2þ and Pb2þ extractants has been
assessed.
2. Results and discussion
Structures of the new di-ionizable calyx[4]arene-1,2-crown-
1
5 and -crown-6 ligands were verified by IR spectroscopy, H,
2.1. Synthetic routes
and 13C NMR spectroscopy and combustion analysis. Cone
conformations of the calix[4]arene units in di-ionizable calix-
crowns 6e15 were verified by NMR spectroscopy. There
were no peaks between 36 and 40 ppm in the 13C NMR
spectrum, revealing that all four benzene rings have syn
arrangements.11
Calix[4]arene (1), tetraethylene glycol dimesylate, and
pentaethylene glycol ditosylate were prepared according to
reported methods.8e10 Calix[4]arene-1,2-crown-5 (2) and
calix[4]aene-1,2-crown-6 (3) (Scheme 1) were synthesized
by modification of reported procedures.5f For the preparation
of 2, the reaction time was extended from 10 to 72 h and
tetraethylene glycol ditosylate was replaced with tetraethylene
glycol dimesylate, giving a 56% yield. For 3, the reaction time
was extended from 10 to 16 h, increasing the yield by 15%.
Calixcrown 3 was refluxed with ethyl bromoacetate and
NaH in THFeDMF (9:1) to give diester 5 in 80% yield.
The yield of 5 depended on the amount of calixcrown 3
used in the reaction. The greater the amount of 3 employed,
the lower was the percentage yield of diester 5 obtained.
Alkylation of calixcrown 2 was found to be surprisingly
difficult. The procedure that was used successfully to alkylate
calix[4]arene-1,2-crown-6 (3) described above was ineffective.
The reaction mixture was brown-black and TLC analysis
showed a very complex product mixture. No reaction was
evident when KH replaced NaH as the base.
2.2. Competitive solvent extraction of alkaline earth metal
cations
Plots of metal ion loadings of the organic phase versus the
equilibrium pH of the aqueous phase for competitive solvent
extractions of aqueous alkaline earth metal cation (10.0 mM
in each) solutions by 1.0 mM solutions of di-ionizable
calix[4]arene-1,2-crown-5 ligands 6, 8e11 in chloroform
are presented in Figure 2.12 Note that the metals loadings
were negligible when the aqueous phases were highly acidic.
This verifies that the extractants are ineffective in their neu-
tral, non-ionized forms. The di-ionizable calix[4]arene-1,2-
crown-5 ligands gave 93e100% maximum metals loadings
(for formation of 1:1 di-ionized ligandemetal ion extraction
complexes). Although the dicarboxylic acid ligand 6 shows lit-
tle selectivity (Fig. 2a), the change to N-(X)sulfonyl carbox-
amide acidic functions in ligands 8e11 (Fig. 2bee) gave
extraction selectivity for Ba2þ over the other three alkaline
earth metal ion species. For ligands 8e11, the selectivity
order was Ba2þ>Sr2þ>Ca2þ>Mg2þ, the same order as the de-
creasing metal cation size. With variation of the X group in the
order of CH3, C6H5, C6H4-4-NO2, and CF3, the ligand acidity is
expected to increase as the electron-withdrawing power of the
X is enhanced. The pH for half loading, pH0.5, is a qualitative
measure of the ligand acidity. For compounds 8e11, the
pH0.5 values are 7.1, 7.0, 6.2, and 4.2, respectively, which is
in accord with the electron-withdrawing power of the X group.
For the analogous di-ionizable calix[4]arene-1,2-crown-6
ligands 7 and 12e15 (Fig. 3), less efficient metals loadings
(78e83% maximum metals loadings for formation of 1:1
Using DMF as the solvent and performing the reaction at
70 ꢀC for 24 h gave a trace of the desired diester 4. Extending
the reaction time to 72 h gave a 25% yield of diester 4. A
longer reaction time did not increase the yield further. From
O
O
O
O
Ba2+
O
O
-N
-N
O
O
O
O
S
S
O
O
X
X
Figure 1. Proposed Ba2þ extraction complex with di-ionized N-(X)sulfonyl
carboxamide calix[4]arene-1,2-crown-4 ligands.

C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
1189
a
b
c
O
O
H2C
O C
O
O
HO
O
OH OH
n
OH
O
O
CH2
O C
OH
OH
O
O
O
O
1
O
O
O
5 C2H5
n
n
2
1
2
C2H
3
n
4
1
2
5
d
Compound
8
n
X
CH3
C6H5
O
O
H2C
O
O
O
H2C
C
O
1
1
1
1
2
2
2
2
O
O
CH2
C
9
CH2
O C
O
O
10
11
12
13
14
15
C6H4-4-NO2
CF3
O C
O
O
O
O
OH
O
OH
CH3
C6H5
NH
O
n
NH
SO2
n
SO2
X
C6H4-4-NO2
CF3
n
1
2
X
6
7
Scheme 1. Synthesis of di-ionizable calix[4]arene-1,2-crown-5 and crown-6 ligands in the cone conformation (6e15). (a) (i) n¼1: Ms(OCH2CH2)4OMs, NaH,
DMF, 50 ꢀC, 72 h; (ii) n¼2: Ts(OCH2CH2)5OTs, NaH, DMF, 50 ꢀC, 16 h; (b) (i) n¼1: NaH, BrCH2CO2C2H5, DMF, 80 ꢀC, 72 h; (ii) n¼2: NaH, BrCH2CO2C2H5,
THFeDMF (9:1), reflux, 24 h; (c) (i) 10% Me4NþOHꢁ (aq), THF, reflux, 24 h; (ii) 6 N HCl (aq); (d) (i) ClC(O)C(O)Cl, benzene, reflux, 5 h; (ii) NaH, NH2SO2X,
THF, rt, 24 h.
di-ionized ligandemetal ion extraction complexes)12 were ob-
served, compared with their crown-5 analogues. As before,
the calixcrown dicarboxylic ligand gave no extraction selectiv-
ity (Fig. 3a). All four alkaline earth metal cations are detectably
extracted into the chloroform phase with the di(N-(X)sulfonyl
carboxamide)s 12e15 (Fig. 3bee). The extraction selectivity
order was Ba2þ>Sr2þ>Ca2þ>Mg2þ, the same as those of
calix[4]arene-1,2-crown-5 analogues. For compounds 12e15,
the pH0.5 values were 7.5, 8.1, 6.1, and 3.9, respectively.
When compared with the earlier reported results for alkaline
earth metal cation extraction by di-ionizable calix[4]arene-1,2-
crown-4 analogues,7c it is noted that for the three dicarboxylic
acid ligands only the crown-4 ligand exhibits appreciable
extraction selectivity. For the calixcrown N-(X)sulfonyl oxy-
acetamides, all show Ba2þ extraction selectivity. However,
the selectivity is considerably greater with the crown-4 extrac-
tant than for the crown-5 and crown-6 analogues. Thus expan-
sion of the polyether ring size to better accommodate Ba2þ
Figure 2. Percent metals loadings versus equilibrium pH of the aqueous phase for competitive solvent extraction of alkaline earth metal ions into chloroform by
di-ionizable calix[4]arene-1,2-crown-5 ligands: (a) 6, (b) 8, (c) 9, (d) 10, and (e) 11 (,¼Mg2þ; B¼Ca2þ
;
¼Sr2þ
;
¼Ba2þ).12
6
;

1190
C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
Figure 3. Percent metals loadings versus equilibrium pH of the aqueous phase for competitive solvent extraction of alkaline earth metal ions into chloroform by
di-ionizable calix[4]arene-1,2-crown-6 ligands: (a) 7, (b) 12, (c) 13, (d) 14, and (e) 15 (,¼Mg2þ; B¼Ca2þ
;
¼Sr2þ
;
¼Ba2þ).12
6
;
within the cavity does not lead to improved extraction
selectivity.
N-(X)sulfonyl carboxamides 8e11, the extraction efficiency
decreases as X is varied in the order: CF3>4-NO2C6H4>CH3,
C6H5. This is the order of decreasing electron-withdrawing
ability of X.
Expanding the polyether ring size from crown-5 to crown-6
produces the extraction profiles shown in Figure 5c for di-
ionizable calix[4]arene-1,2-crown-6 ligands 7 and 12e15. In
general, it appears that this structural modification leads to
less efficient extractants. Only with the dicarboxylic acid
extractant 7 and the di(N-(X)-sulfonyl carboxamide) ligands
with X¼CF3 and 4-NO2C6H4 are Pb2þ loadings of 90% or
greater obtained.
Comparison of the extraction data presented in Figure 5a
and b allows the effect of introducing a p-tert-butyl group
on each aromatic group in the ligands to be assessed. As can
be seen, the extraction profiles for di-ionizable p-tert-butylca-
lix[4]arene-1,2-crown-5 ligands 16e20 (Fig. 5b) and their di-
ionizable calix[4]arene-1,2-crown-5 analogues 6 and 8e11 are
very similar both in terms of extraction efficiencies and the
effect of the X variation for the N-(X)sulfonyl carboxamide
groups.
Examination of the extraction profiles shown in Figure 5c
and d reveals that the addition of four p-tert-butyl groups to
the upper rim of di-ionizable calix[4]arene-1,2-crown-6
ligands increases the efficiency of Pb2þ extraction. For all
five of the more lipophilic ligands 21e25, quantitative levels
of Pb2þ extraction were achieved.
In previous studies,7c,13 we found that calix[4]arenes with
pendant N-(X)sulfonyl carboxamide groups are effective not
only in extraction of hard metal cations, but also exhibit
high extraction efficiency and selectivity for some intermedi-
ate (Pb2þ) and soft (Hg2þ) metal ions.13 Therefore, single spe-
cies solvent extractions of Pb2þ and of Hg2þ by ligands 6e15
and analogues 16e257b (Fig. 4) were performed. For the latter
series, the structural modification is introduction of four lipo-
philic tert-butyl groups on the upper rim.
2.3. Solvent extraction of Pb2þ
Plots of Pb2þ loading of the organic phase versus the equilib-
rium pH of the aqueous phase for competitive solvent extrac-
tions of aqueous Pb(NO3)2 (1.0 mM) solutions by 0.50 mM
solutions of di-ionizable calix[4]arene-1,2-crown-5 ligands 6
and 8e11 in chloroform are presented in Figure 5a. All five
ligands exhibit high extraction ability toward Pb2þ with quan-
titative or nearly quantitative loading for formation of
1:1 di-ionized ligandePb2þ extraction complexes. For the
Bu-t
t-Bu
Compound
n
X
OH
Bu-t Bu-t
16
17
18
19
20
21
22
23
24
25
1
1
1
1
1
2
2
2
2
2
NHSO2CH3
NHSO2C6H5
NHSO2C6H4-4-NO2
NHSO2CF3
OH
O
O
O
O
H2C
O
NHSO2CH3
NHSO2C6H5
NHSO2C6H4-4-NO2
NHSO2CF3
CH2
2.4. Solvent extraction of Hg2þ
O
O
C
O
C
X
X
O
Plots of Hg2þ loading of the organic phase versus the equi-
librium pH of the aqueous phase for competitive solvent
extractions of aqueous Hg(NO3)2 (0.25 mM) solutions by
n
Figure 4. Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 and -crown-6
ethers 16e25.

C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
1191
Figure 5. Percent metal loading of the organic phase versus the equilibrium pH of the aqueous phase for single species solvent extraction of Pb2þ by ligands: (a)
6 (,), 8 (B), 9 ( ), 10 ( ), 11 (>); (b) 16 (,), 17 (B), 18 ( ), 19 ( ), 20 (>); (c) 7 (,), 12 (B), 13 ( ), 14 ( ), 15 (>); (d) 21 (,), 22 (B),
23 ( ), 24 ( ), 25 (>).
6
6
6
;
;
;
6
;
0.25 mM solutions of di-ionizable calix[4]arene-1,2-crown-5
ligands 6 and 8e11 in chloroform are presented in
Figure 6a. Although the Hg2þ extraction efficiency for dicarb-
oxylic acid ligand 6 was only modest, those for the di(N-
(X)sulfonyl carboxamide) ligands 8e11 were very high with
quantitative or nearly quantitative Hg2þ loading. Contrary to
the findings for extractions of alkaline earth metal cations
and of Pb2þ, the least efficient extraction now was observed
when X¼CF3, with little discernable variation for the other
three X groups. Presumably this difference arises from the
soft nature of Hg2þ compared to the other divalent metal ion
species examined.
Comparison of the extraction profiles presented in Figure 6a
with those for di-ionizable calix[4]arene-1,2-crown-6
compounds 7 and 12e15 (Fig. 6c) reveals only minor changes
when the polyether rings of the ligands were expanded from
crown-5 to crown-6. This contrasts with the results presented
earlier for alkaline earth metal cation and Pb2þ extractions by
the same two series of ligands for which this ring size expan-
sion produced diminished extraction selectivity and/or
efficiency.
To examine the influence of lipophilic p-tert-butyl groups
on the upper rims of both the crown-5 and crown-6 ligands
in Hg2þ, compare the profiles given in Figure 6b with a and
Figure 6. Percent metals loading of the organic phase versus the equilibrium pH of the aqueous phase for single species solvent extraction of Hg2þ by ligands: (a)
6 (,), 8 (B), 9 ( ), 10 ( ), 11 (>); (b) 16 (,), 17 (B), 18 ( ), 19 ( ), 20 (>); (c) 7 (,), 12 (B), 13 ( ), 14 ( ), 15 (>); (d) 21 (,), 22 (B),
23 ( ), 24 ( ), 25 (>).
6
6
6
;
;
;
6
;

1192
C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
d with c, respectively. With the exception of the p-tert-butylca-
lixarene-1,2-crown-5 and -crown-6 compounds, 16 and 21,
respectively, for which this structural variation is markedly
detrimental, the profiles are remarkably similar for the four
series of ligands with N-(X)sulfonyl carboxamide groups.
Anal. Calcd for C44H50O11$0.3CH2Cl2: C, 69.37; H, 6.65.
Found: C, 69.22; H, 6.77.
3.1.2. 25,26-Bis[(ethoxycarbony)methoxyl]calix[4]arene-
1,2-crown-6 in the cone conformation (5)
A mixture of NaH (10.00 equiv, 0.65 g, 27.1 mmol), 25,26-
dihydroxycalix[4]-arene-crown-6 (3) (1.00 equiv, 1.70 g,
2.71 mmol), and 45 mL of THFeDMF (9:1) in a 100-mL,
one-necked flask under nitrogen was stirred for 30 min. Ethyl
bromoacetate (8.00 equiv, 3.62 g, 21.68 mmol) was added to
the flask with a syringe. The mixture was refluxed for 24 h.
The reaction was quenched by addition of 1 N HCl (10 mL).
THF was evaporated in vacuo and 1 N HCl (75 mL) was added
to the residue. The resulting aqueous solution was extracted
with CH2Cl2 (100 mL). The organic layer was separated,
washed with H2O (100 mL), and dried over MgSO4. The
CH2Cl2 was evaporated in vacuo. The crude product was chro-
matographed on silica gel with hexaneseEtOAc (1:2) as eluent
to give 1.72 g (80%) of pale yellow, viscous oil. IR: 1758
3. Experimental
3.1. General
Ligands 16e25 were prepared by the reported methods.7b
Reagents were obtained from commercial suppliers and used
directly, unless otherwise noted. THF was dried over sodium
wire with benzophenone ketyl as an indicator. DMF was stored
˚
over 4 A molecular sieves. Infrared spectral analyses were per-
formed with a PerkineElmer 1600 FTIR spectrophotometer
by deposit from CH2Cl2 solution onto a NaCl plate. The
absorptions are expressed in wavenumbers (cmꢁ1). NMR
spectra were measured with a Varian Unity Inova FT-500 spec-
trometer (499.7 MHz for 1H and 125.7 MHz for 13C) at 296 K
in CDCl3 with TMS as an internal standard. Chemical shifts
(d) are expressed in parts per million downfield from TMS
and coupling constants (J ) values are given in hertz. Melting
points were determined with a Mel-Temp melting point appa-
ratus. Combustion analysis was performed by Desert Analytics
Laboratory of Tucson, Arizona.
1
(C]O), 1246, 1093, 1066 (CeO) cmꢁ1. H NMR: d 6.80e
6.30 (m, 12H, ArH), 4.80 (d, J¼13.4 Hz, 1H, ArCH2Ar, ax),
4.74 (d, J¼16.2 Hz, 2H, OCH2C(O)), 4.68 (d, J¼17.1 Hz,
2H, OCH2C(O)), 4.65 (d, J¼13.7 Hz, 2H, ArCH2Ar, ax), 4.60
(d, J¼13.4 Hz, 1H, ArCH2Ar, ax), 4.22 (q, J¼7.1 Hz, 4H,
OCH2CH3), 4.18e4.07 (m, 4H, OCH2), 4.07e3.98 (m, 2H,
OCH2), 3.96e3.85 (m, 2H, OCH2), 3.79e3.60 (m, 12H,
OCH2), 3.24 (d, J¼13.7 Hz, 1H, ArCH2Ar, eq), 3.19 (d,
J¼13.6 Hz, 2H, ArCH2Ar, eq), 3.15 (d, J¼13.4 Hz, 1H,
ArCH2Ar, eq), 1.30 (t, J¼7.1 Hz, 6H, CH3). 13C NMR:
d 170.0 (C]O), 156.3, 155.6, 135.2, 134.8, 134.8, 134.4,
128.5, 128.4, 128.3, 128.1, 122.8, 122.3 (Ar), 73.2 (OCH2),
71.2 (OCH2C(O)), 70.9, 70.9, 70.5, 70.3 (OCH2), 60.5
(OCH2CH3), 31.4, 31.0, 30.8 (ArCH2Ar), 14.2 (CH3). Anal.
Calcd for C46H54O12: C, 69.16; H, 6.81. Found: C, 68.83;
H, 7.05.
3.1.1. 25,26-Bis[(ethoxycarbonyl)methoxy]calix[4]arene-
1,2-crown-5 in the cone conformation (4)
To a stirred mixture of NaH (10.00 equiv, 2.04 g, 85 mmol)
and DMF (20 mL) in a 250-mL, three-necked flask under
nitrogen was added dropwise a solution of 25,26-dihydroxy
calix[4]arene-crown-5 (2) (1.00 equiv, 4.95 g, 8.50 mmol) in
DMF (100 mL). The mixture was stirred for 1 h. A solution
of ethyl bromoacetate (8.00 equiv, 11.36 g, 7.54 mL,
68 mmol) in DMF (10 mL) was added over a 1-h period.
The mixture was stirred for 72 h at 80 ꢀC. The reaction was
quenched by addition of 1 N HCl (20 mL) at 0 ꢀC. The solvent
was evaporated in vacuo. CH2Cl2 (100 mL) was added to the
residue. The resulting organic solution was washed with
H2O (2ꢂ100 mL) and dried over MgSO4. After filtration,
the filtrate was evaporated in vacuo. The resulting solid was
chromatographed on flash silica gel with hexaneseEtOAc
(3:2) as eluent to give 1.73 g (27%) of pale yellow solid
with a melting point of 51e53 ꢀC. IR: 1757 (C]O), 1266,
3.1.3. 25,26-Bis(carboxymethoxy)calix[4]arene-1,2-crown-
5 in the cone conformation (6)
A solution of 25,26-bis[(ethoxycarbonyl)methoxy]calix[4]-
arene-crown-5 (4) (1.70 g, 2.25 mmol) in THF (20 mL) was
mixed with 20 mL of 10% aqueous Me4NOH. The mixture
was refluxed for 24 h. After cooling to room temperature,
the reaction was quenched by addition of 6 N HCl (10 mL).
The mixture was stirred for 1 h. The organic solvent was evap-
orated in vacuo and the precipitate was filtered. The precipitate
was dissolved in CH2Cl2 (50 mL). The aqueous filtrate was
extracted with CH2Cl2 (2ꢂ30 mL). The combined CH2Cl2 so-
lutions were dried over MgSO4 and evaporated in vacuo to
give 1.51 g (96%) of white solid with a melting point of
128e130 ꢀC. IR: 3500e2700 (br, CO2H), 1752 (C]O),
1095, 1064 (CeO) cmꢁ1. H NMR: d 6.73e6.52 (m, 12H,
1
ArH), 4.87 (d, J¼13.4 Hz, 1H, ArCH2Ar, ax), 4.75 (s, 4H,
OCH2C(O)), 4.61 (d, J¼13.6 Hz, 2H, ArCH2Ar, ax), 4.58 (d,
J¼15.2 Hz, 1H, ArCH2Ar, ax), 4.22 (q, J¼7.1 Hz, 4H,
OCH2CH3), 4.30e4.10 (m, 2H, OCH2), 4.09e3.92 (m, 6H,
OCH2), 3.80e3.59 (m, 8H, OCH2), 3.23 (d, J¼13.4 Hz, 1H,
ArCH2Ar, eq), 3.22 (d, J¼13.5 Hz, 2H, ArCH2Ar, eq), 3.14
(d, J¼13.4 Hz, 1H, ArCH2Ar, eq), 1.29 (t, J¼7.2 Hz, 6H,
CH3). 13C NMR: d 170.1 (C]O), 156.2, 155.6, 135.3,
134.7, 134.6, 128.4, 128.4, 128.3, 128.2, 122.7, 122.3 (Ar),
73.5 (OCH2), 71.3 (OCH2C(O)), 71.2, 70.6, 70.3 (OCH2),
60.5 (OCH2CH3), 31.2, 31.2, 30.6 (ArCH2Ar), 14.2 (CH3).
1
1248, 1130, 1058 (CeO) cmꢁ1. H NMR: d 10.17 (br s, 2H,
CO2H), 7.00e6.50 (m, 12H, ArH), 4.78 (d, J¼16.1 Hz, 2H,
OCH2C(O)), 4.65 (d, J¼15.9 Hz, 2H, OCH2C(O)), 4.65 (d,
J¼15.9 Hz, 1H, ArCH2Ar, ax), 4.61 (d, J¼13.8 Hz, 1H,
ArCH2Ar, ax), 4.35 (d, J¼13.2 Hz, 2H, ArCH2Ar, ax),
4.29e4.15 (m, 2H, OCH2), 4.15e4.04 (m, 2H, OCH2),
4.04e3.86 (m, 4H, OCH2), 3.86e3.73 (m, 4H, OCH2),

C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
1193
3.73e3.59 (m, 4H, OCH2), 3.30 (d, J¼11.5 Hz, 1H, ArCH2Ar,
eq), 3.28 (d, J¼13.3 Hz, 2H, ArCH2Ar, eq), 3.18 (d,
J¼13.2 Hz, 1H, ArCH2Ar, eq). 13C NMR: d 172.0 (C]O),
155.0, 154.7, 135.4, 134.1, 134.0, 133.9, 128.9, 128.9,
128.6, 128.5, 123.8, 123.1 (Ar), 74.6 (OCH2), 71.6
(OCH2C(O)), 70.9, 70.4, 69.8 (OCH2), 31.1, 30.8, 30.4
(ArCH2Ar). Anal. Calcd for C40H42O11: C, 68.76; H, 6.06.
Found: C, 68.94; H, 6.11.
(10 mL) was added and stirring was continued for 0.5 h. The
THF was evaporated in vacuo. CH2Cl2 was added to the residue
and the resulting solution was dried over MgSO4. After purifi-
cation by chromatography on silica gel, the product was
dissolved in CH2Cl2. The solution was shaken with 6 N HCl,
dried over MgSO4, and evaporated in vacuo to provide the
product as a solid.
3.2.1. 25,26-Bis(N-methanesulfonyl carbamoylmethoxy)-
calix[4]arene-1,2-crown-5 in the cone conformation (8)
Compound 8 was chromatographed on silica gel with
CH2Cl2eMeOH (97:3) as eluent to obtain 0.67 g (42%) of
white solid with a melting point of 291e293 ꢀC. IR: 3218
(NeH), 1721 (C]O), 1344, 1140 (SO2), 1266, 1093, 1057
3.1.4. 25,26-Bis(carboxymethoxy)calix[4]arene-1,2-crown-
6 in the cone conformation (7)
A solution of 25,26-bis[(ethoxycarbonyl)methoxy]calix[4]-
arene-crown-6 (5) (1.70 g, 2.13 mmol) in THF (30 mL) was
mixed with 10% aqueous Me4NOH (30 mL). The mixture
was refluxed for 24 h. After cooling to room temperature,
the reaction was quenched by addition of 6 N HCl (15 mL).
The mixture was stirred for 1 h. The organic solvent was evap-
orated in vacuo and the precipitate was filtered. The precipitate
was dissolved in CH2Cl2 (50 mL). The aqueous filtrate was
extracted with CH2Cl2 (2ꢂ30 mL). The combined CH2Cl2
solutions were dried over MgSO4 and evaporated in vacuo to
give 1.55 g (98%) of white solid with a melting point of
120e122 ꢀC. IR: 3400e2700 (br, CO2H), 1757 (C]O),
1
(CeO) cmꢁ1. H NMR: d 10.22 (s, 2H, NH), 7.00e6.31 (m,
12H, ArH), 4.95 (d, J¼16.1 Hz, 2H, OCH2C(O)), 4.92 (d,
J¼13.2 Hz, 1H, ArCH2Ar, ax), 4.58 (d, J¼16.4 Hz, 2H,
OCH2C(O)), 4.12 (d, J¼13.3 Hz, 1H, ArCH2Ar, ax), 4.38 (d,
J¼13.9 Hz, 2H, ArCH2Ar, ax), 4.20e3.98 (m, 6H, OCH2),
3.98e3.82 (m, 4H, OCH2), 3.82e3.65 (m, 6H, OCH2), 3.35
(s, 6H, CH3), 3.30 (d, J¼13.8 Hz, 2H, ArCH2Ar, eq), 3.27
(d, J¼10.7 Hz, 1H, ArCH2Ar, eq), 3.19 (d, J¼13.3 Hz, 1H,
ArCH2Ar, eq). 13C NMR: d 170.2 (C]O), 155.9, 155.8,
134.8, 134.8, 134.0, 133.1, 129.3, 128.6, 128.6, 128.5,
123.2, 122.8 (Ar), 74.0 (OCH2), 73.4 (OCH2C(O)), 69.9,
69.6, 69.4 (OCH2), 41.5 (CH3), 31.6, 31.2, 30.6 (ArCH2Ar).
Anal. Calcd for C42H48O13N2S2$0.1CH2Cl2: C, 58.70; H,
5.64; N, 3.25. Found: C, 58.53; H, 5.71; N, 3.10.
1
1273, 1130, 1062 (CeO) cmꢁ1. H NMR: d 10.14 (br s, 2H,
CO2H), 6.99e6.50 (m, 12H, ArH), 4.78 (d, J¼16.1 Hz, 2H,
OCH2C(O)), 4.65 (d, J¼13.3 Hz, 1H, ArCH2Ar, ax), 4.61 (d,
J¼16.0 Hz, 2H, OCH2C(O)), 4.61 (d, J¼16.0 Hz, 1H,
ArCH2Ar, ax), 4.40 (d, J¼13.2 Hz, 2H, ArCH2Ar, ax),
4.28e4.08 (m, 4H, OCH2), 4.06e3.93 (m, 2H, OCH2),
3.93e3.83 (m, 2H, OCH2), 3.83e3.53 (m, 12H, OCH2),
3.31 (d, J¼13.7 Hz, 1H, ArCH2Ar, eq), 3.26 (d, J¼13.3 Hz,
2H, ArCH2Ar, eq), 3.20 (d, J¼13.3 Hz, 1H, ArCH2Ar, eq).
13C NMR: d 171.7 (C]O), 155.2, 154.7, 135.2, 134.2,
134.2, 133.8, 128.9, 128.9, 128.7, 128.2, 123.8, 123.0 (Ar),
74.3 (OCH2), 71.6 (OCH2C(O)), 70.9, 70.8, 70.3, 69.7
(OCH2), 31.1, 30.7 (ArCH2Ar). Anal. Calcd for C42H46O12:
C, 67.91; H, 6.24. Found: C, 67.58; H, 6.54.
3.2.2. 25,26-Bis(N-benzenesulfonyl carbamoylmethoxy)-
calix[4]arene-1,2-crown-5 in the cone conformation (9)
Compound 9 was chromatographed on silica gel with
CH2Cl2eMeOH (39:1) as eluent to obtain 1.19 g (65%) of
white solid with a melting point of 146e147 ꢀC. IR: 3228
(NeH), 1715 (C]O), 1350, 1154 (SO2), 1265, 1087, 1051
(CeO) cmꢁ1 1H NMR: d 10.43 (s, 2H, NH), 8.14 (d,
.
J¼7.6 Hz, 4H, ArH), 7.61 (t, J¼7.4 Hz, 2H, ArH), 7.50 (t,
J¼7.8 Hz, 4H, ArH), 7.09e6.10 (m, 12H, ArH), 4.66
(d, J¼15.7 Hz, 2H, OCH2C(O)), 4.48 (d, J¼13.5 Hz, 1H,
ArCH2Ar, ax), 4.40 (d, J¼15.7 Hz, 2H, OCH2C(O)), 4.38 (d,
J¼12.9 Hz, 1H, ArCH2Ar, ax), 4.31 (d, J¼14.8 Hz, 2H,
ArCH2Ar, ax), 4.26e4.11 (m, 2H, OCH2), 4.11e3.87 (m, 8H,
OCH2), 3.87e3.63 (m, 6H, OCH2), 3.19 (d, J¼13.3 Hz, 1H,
ArCH2Ar, eq), 3.12 (d, J¼13.7 Hz, 2H, ArCH2Ar, eq), 2.96
(d, J¼13.4H, 1H, ArCH2Ar, eq). 13C NMR: d 168.7 (C]O),
155.9, 155.7, 138.8, 134.9, 134.6, 134.0, 133.9, 132.8, 128.9,
128.9, 128.5, 128.4, 123.0, 122.8 (Ar), 74.4 (OCH2), 73.2
(OCH2C(O)), 69.6, 69.4 (OCH2), 32.1, 31.0, 30.8 (ArCH2Ar).
Anal. Calcd for C52H52O13N2S2: C, 63.92; H, 5.36; N, 2.87.
Found: C, 63.73; H, 5.57; N, 2.85.
3.2. General procedure for the synthesis of 25,26-di(N-
(X)sulfonyl carbamoylmethoxy)calix[4]arene-1,2-crown-
5 compounds in the cone conformation (8e11)
A solution of 25,26-bis(carboxymethoxy)calix[4]arene-
crown-5 (6) (1.00 equiv, 1.31 g, 1.875 mmol) in benzene
(90 mL) was refluxed with a Dean-Stark trap for 2 h during
which 50 mL of benzene was removed. Oxalyl chloride
(11.00 equiv, 2.62 g, 1.77 mL, 20.6 mmol) was added to the
flask with a syringe and the mixture was refluxed for 5 h under
nitrogen. The benzene was evaporated in vacuo to give the
corresponding di(acid chloride), which was used directly in
the next step. The sulfonamide salt was prepared under nitrogen
by adding NaH (10.00 equiv, 0.45 g, 18.75 mmol) and THF
(20 mL) to a 3-necked flask. The appropriate sulfonamide
(2.2 equiv, 4.12 mmol) in THF (30 mL) was added over a
10-min period. The mixture was stirred for 1.5 h followed by
addition of a solution of di(acid chloride) in THF (10 mL).
The reaction mixture was stirred for 24 h after which H2O
3.2.3. 25,26-Bis(N-4-nitrobenzenesulfonylcarbamoylmethoxy)-
calix[4]arene-1,2-crown-5 in the cone conformation (10)
Compound 10 was chromatographed on silica gel with
CH2Cl2eMeOH (39:1) as eluent to give 1.00 g (50%) of yellow
solid with a melting point of 246e248 ꢀC. IR: 3237 (NeH),
1720 (C]O), 1534, 1311 (NO2), 1350, 1153 (SO2), 1266,

1194
C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
1087, 1055 (CeO) cmꢁ1. 1H NMR: d 10.59 (s, 2H, NH), 8.30
(s, 8H, ArH), 6.99e5.60 (m, 12H, ArH), 4.83 (d, J¼15.6 Hz,
2H, OCH2C(O)), 4.60 (d, J¼13.4 Hz, 1H, ArCH2Ar, ax), 4.51
(d, J¼16.1 Hz, 2H, OCH2C(O)), 4.40 (d, J¼13.2 Hz, 1H,
ArCH2Ar, ax), 4.30 (d, J¼13.8 Hz, 2H, ArCH2Ar, ax), 4.20e
4.09 (m, 2H, OCH2), 4.05 (d, J¼7.8 Hz, 4H, OCH2), 3.99e
3.91 (m, 2H, OCH2), 3.91e3.84 (m, 2H, OCH2), 3.84e3.67
(m, 6H, OCH2), 3.21 (d, J¼13.7 Hz, 2H, ArCH2Ar, eq), 3.19
(d, J¼9.8 Hz, 1H, ArCH2Ar, eq), 2.96 (d, J¼13.6 Hz, 1H,
ArCH2Ar, eq). 13C NMR: d 169.0 (C]O), 155.8, 155.5,
150.6, 143.9, 134.6, 133.8, 132.8, 130.0, 129.2, 128.6, 128.4,
124.1, 123.2, 122.9 (Ar), 74.2 (OCH2), 73.2 (OCH2C(O)),
69.7, 69.7, 69.5 (OCH2), 31.9, 31.1, 30.6 (ArCH2Ar). Anal.
Calcd for C52H50O17N4S2: C, 58.53; H, 4.72; N, 5.25. Found:
C, 58.44; H, 4.86; N, 5.05.
The THF was evaporated in vacuo. CH2Cl2 was added to the
residue and the resulting organic solution was dried over
MgSO4. After purification by chromatography on silica gel,
the product was dissolved in CH2Cl2. The solution was shaken
with 6 N HCl, dried over MgSO4, and evaporated in vacuo to
give the product as a solid.
3.3.1. 25,26-Bis(N-methanesulfonyl carbamoylmethoxy)-
calix[4]arene-1,2-crown-6 in the cone conformation (12)
Compound 12 was chromatographed on silica gel with
CH2Cl2eMeOH (19:1) as eluent to give 1.44 g (71%) of white
solid with a melting point of 126e128 ꢀC. IR: 3220 (NeH),
1712 (C]O), 1343, 1152 (SO2), 1266, 1084, 1052
(CeO) cmꢁ1 1H NMR: d 10.19 (s, 2H, NH), 7.00e6.20
.
(m, 12H, ArH), 4.99 (d, J¼12.0 Hz, 1H, ArCH2Ar, ax), 4.96
(d, J¼16.0 Hz, 2H, OCH2C(O)), 4.46 (d, J¼16.5 Hz, 2H,
OCH2C(O)), 4.46 (d, J¼12.0 Hz, 1H, ArCH2Ar, ax), 4.42
(d, J¼14.0 Hz, 2H, ArCH2Ar, ax), 4.23e4.12 (m, 2H, OCH2),
4.08e3.92 (m, 4H, OCH2), 3.87e3.80 (m, 2H, OCH2), 3.80e
3.67 (m, 10H, OCH2), 3.67e3.59 (m, 2H, OCH2), 3.37 (s,
6H, CH3), 3.28 (d, J¼14.0 Hz, 1H, ArCH2Ar, eq), 3.28 (d,
J¼14.0 Hz, 2H, ArCH2Ar, eq), 3.20 (d, J¼14.0 Hz, 1H,
ArCH2Ar, eq). 13C NMR: d 169.9 (C]O), 156.0, 155.9,
134.9, 134.3, 134.2, 133.6, 129.3, 128.6, 128.6, 128.3,
123.2, 122.7 (Ar), 73.7 (OCH2C(O)), 73.6, 70.8, 70.2, 70.0,
69.8 (OCH2), 41.4 (CH3), 31.3, 31.0, 30.7 (ArCH2Ar). Anal.
Calcd for C44H52O14N2S2: C, 58.92; H, 5.84; N, 3.12. Found:
C, 58.60; H, 5.80; N, 2.84.
3.2.4. 25,26-Bis(N-trifluoromethanesulfonyl carbamoyl-
methoxy)calix[4]arene-1,2-crown-5 in the cone
conformation (11)
Compound 11 was chromatographed on silica gel with hexa-
neseEtOAc (1:2) as eluent to give 0.74 g (41%) of white solid
with a melting point of 127e129 ꢀC. IR: 3200e2300 (br,
NeH), 1752 (C]O), 1372, 1206 (SO2), 1265, 1135, 1053
1
(CeO) cmꢁ1. H NMR: d 10.80 (br s, 2H, NH), 6.65 (br s,
12H, ArH), 4.89 (s, 4H, OCH2C(O)), 4.78 (d, J¼13.4 Hz, 1H,
ArCH2Ar, ax), 4.41 (d, J¼13.8 Hz, 2H, ArCH2Ar, ax), 4.37
(d, J¼13.3 Hz, 1H, ArCH2Ar, ax), 4.23 (br s, 2H, OCH2),
4.09e3.94 (m, 6H, OCH2), 3.94e3.84 (m, 4H, OCH2), 3.84e
3.70 (m, 4H, OCH2), 3.31 (d, J¼13.9 Hz, 2H, ArCH2Ar, eq),
3.27 (d, J¼13.8 Hz, 1H, ArCH2Ar, eq), 3.23 (d, J¼13.2 Hz,
1H, ArCH2Ar, eq). 13C NMR: d 168.4 (C]O), 155.8, 155.3,
135.2, 134.5, 134.0, 132.7, 129.1, 128.8, 128.7, 128.6, 123.4,
123.1 (Ar), 120.5, 117.9 (CF3), 74.3 (OCH2), 72.6
(OCH2C(O)), 69.2, 69.0, 68.7 (OCH2), 32.3, 31.0, 30.8
(ArCH2Ar). Anal. Calcd for C42H42O13N2S2F6: C, 52.50; H,
4.40; N, 2.92. Found: C, 52.79; H, 4.60; N, 2.97.
3.3.2. 25,26-Bis(N-benzenesulfonyl carbamoylmethoxy)-
calix[4]arene-1,2-crown-6 in the cone conformation (13)
Compound 13 was chromatographed on silica gel with
CH2Cl2eMeOH (97:3) as eluent to give 1.92 g (83%) of white
solid with a melting point of 107e109 ꢀC. IR: 3231 (NeH),
1716 (C]O), 1350, 1160 (SO2), 1266, 1088, 1058
(CeO) cmꢁ1. 1H NMR: d 10.34 (s, 2H, NH), 8.17 (dd, J¼7.3,
1.3 Hz, 4H, ArH), 7.63 (t, J¼7.3 Hz, 2H, ArH), 7.54 (t,
J¼8.0 Hz, 4H, ArH), 6.90e6.20 (m, 12H, ArH), 4.66 (d,
J¼15.4 Hz, 2H, OCH2C(O)), 4.56 (d, J¼13.8 Hz, 1H,
ArCH2Ar, ax), 4.50 (d, J¼13.9 Hz, 1H, ArCH2Ar, ax), 4.38
(d, J¼13.7 Hz, 2H, ArCH2Ar, ax), 4.38 (d, J¼15.4 Hz,
2H, OCH2C(O)), 4.27e4.15 (m, 2H, OCH2), 4.15e4.02 (m,
2H, OCH2), 3.94e3.80 (m, 2H, OCH2), 3.80e3.65 (m, 6H,
OCH2), 3.65e3.44 (m, 8H, OCH2), 3.18 (d, J¼13.9 Hz, 1H,
ArCH2Ar, eq), 3.18 (d, J¼13.9 Hz, 2H, ArCH2Ar, ax), 2.95
(d, J¼13.9 Hz, 1H, ArCH2Ar, ax). 13C NMR: d 168.3 (C]O),
156.2, 155.8, 138.7, 135.0, 134.3, 133.9, 133.6, 132.6, 129.1,
129.1, 128.9, 128.7, 128.7, 128.6, 128.2, 123.1, 122.6 (Ar),
74.0 (OCH2C(O)), 73.9, 71.0, 70.5, 70.4, 70.1 (OCH2), 31.3,
31.1, 31.0 (ArCH2Ar). Anal. Calcd for C54H56O14N2S2:
C, 63.52; H, 5.53; N, 2.74. Found: C, 63.19; H, 5.60; N, 2.79.
3.3. General procedure for the synthesis of 25,26-di[N-
(X)sulfonyl carbamoylmethoxy]calix[4]arene-1,2-crown-
6 compounds in the cone conformation (12e15)
A solution of 25,26-bis(carboxymethoxy)calix[4]arene-
crown-6 (7) (1.00 equiv, 1.68 g, 2.26 mmol) in benzene
(90 mL) was refluxed with a Dean-Stark strap for 2 h during
which 50 mL of benzene was removed. Oxalyl chloride
(11.00 equiv, 3.16 g, 2.14 mL, 24.88 mmol) was added to the
flask with a syringe and the mixture was refluxed for 5 h under
nitrogen. Benzene was evaporated in vacuo to give the corre-
sponding di(acid chloride), which was used directly in the
next step. The sulfonamide salt was prepared under nitrogen
by adding NaH (10.00 equiv, 0.54 g, 22.6 mmol) and THF
(25 mL) to a three-necked flask. The appropriate sulfonamide
(2.2 equiv, 4.97 mmol) in THF (30 mL) was added over
a 10-min period. The mixture was stirred for 1.5 h followed
by addition of a solution of the di(acid chloride) in THF
(10 mL). The reaction mixture was stirred for 24 h after which
H2O (10 mL) was added and stirring was continued for 0.5 h.
3.3.3. 25,26-Bis(N-p-nitrobenzenesulfonyl carbamoylmeth-
oxy)calix[4]arene-1,2-crown-6 in the cone conformation
(14)
Compound 14 was chromatographed on silica gel with
CH2Cl2eMeOH (39:1) as eluent to give 2.03 g (81%) of yellow

C. Tu et al. / Tetrahedron 64 (2008) 1187e1196
1195
solid with a melting point of 183e185 ꢀC. IR: 3226 (NeH),
1725 (C]O), 1537, 1314 (NO2), 1355, 1194 (SO2), 1254,
1086, 1052 (CeO) cmꢁ1. 1H NMR: d 10.67 (s, 2H, NH), 8.40
(d, J¼8.8 Hz, 4H, ArH), 8.36 (d, J¼8.8 Hz, 4H, ArH), 6.60
(s, 10H, ArH), 6.48 (s, 2H, ArH), 4.74 (d, J¼15.6 Hz, 2H,
OCH2C(O)), 4.57 (d, J¼13.9 Hz, 1H, ArCH2Ar, ax), 4.52 (d,
J¼14.2 Hz, 1H, ArCH2Ar, ax), 4.48 (d, J¼15.7 Hz, 2H,
OCH2C(O)), 4.40 (d, J¼13.8 Hz, 2H, ArCH2Ar, ax),
4.31e4.18 (m, 2H, OCH2), 4.16e4.03 (m, 2H, OCH2),
3.92e3.82 (m, 2H, OCH2), 3.82e3.67 (m, 6H, OCH2), 3.66e
3.55 (m, 4H, OCH2), 3.54e3.40 (m, 4H, OCH2), 3.24 (d,
J¼13.9 Hz, 2H, ArCH2Ar, eq), 3.22 (d, J¼13.7 Hz, 1H,
ArCH2Ar, eq), 2.99 (d, J¼13.9 Hz, 1H, ArCH2Ar, eq). 13C
NMR: d 168.6 (C]O), 156.2, 155.5, 150.7, 143.9, 134.9,
134.1, 133.5, 130.1, 129.2, 128.7, 128.7, 128.2, 124.1, 123.2,
122.7 (Ar), 73.9 (OCH2), 73.6 (OCH2C(O)), 70.8, 70.6, 70.4,
70.0 (OCH2), 31.4, 31.0 (ArCH2Ar). Anal. Calcd for
C54H54O18N4S2: C, 58.37; H, 4.90; N, 5.04. Found: C, 58.24;
H, 4.88; N, 5.03.
phase from stripping were determined with a Dionex DX-120
Ion Chromatograph with a CS12A column. The pH of the
aqueous phase from the initial extraction step was deter-
mined with a Fisher Accumet AR25 pH meter with a Corning
476157 combination pH electrode.
3.5. Procedure for single species extraction of Pb2þ
The procedure used for competitive extraction of alkaline
earth metal cations was modified, as follows. The organic
phase was a 0.50 mM solution of the ligand in chloroform.
The aqueous phase contained 1.0 mM Pb(NO3)2 with the pH
adjusted using either HNO3 or Me4NOH solutions. For strip-
ping of the extracted Pb2þ from the chloroform phase, 1.0 M
HNO3 was utilized. The Pb2þ concentrations in the aqueous
stripping solutions were determined with a PerkineElmer
Model 5000 atomic absorption spectrophotometer.
3.6. Procedure for single species extraction of Hg2þ
3.3.4. 25,26-Bis(N-trifluoromethanesulfonylcarbamoylmeth-
oxy)calix[4]arene-1,2-crown-6 in the cone conformation (15)
Compound 15 was chromatographed on silica gel with
CH2Cl2eMeOH (97:3) as eluent to give 1.29 g (57%) of white
solid with a melting point of 181e183 ꢀC. IR: 3401 (NeH),
1752 (C]O), 1389, 1215 (SO2), 1266, 1133, 1055
An aqueous solution (3.0 mL) of 0.25 mM Hg(NO3)2 with
HNO3 or TMAOH for pH adjustment and 3.0 mL of 0.25 mM
solution of the ligand in chloroform were placed in a capped,
polypropylene, 15-mL centrifuge tube. The mixture was vor-
texed for 10 min at room temperature. The tube was centri-
fuged for 10 min for phase separation. A 0.50-mL sample of
the aqueous phase was removed and diluted to 5.0 mL with
water. A 1.5-mL aliquot of the diluted solution was shaken
for 10 min with 3.0 mL of 14 ppm solution of dithizone in
chloroform and 1.5 mL of 1.0 M citric acid solution for which
the pH had been adjusted using NaOH. The mixture was
centrifuged for 10 min. The organic phase was then analyzed
by using the absorbance at 496 nm for mercury dithizonate
complex with a Shimadzu Model 260 UVevis spectrophoto-
meter. The pH of the remaining aqueous phase from the initial
extraction step was determined with a Fisher Accumet AR25
pH meter with a Corning 476157 combination pH electrode.
1
(CeO) cmꢁ1. H NMR: d 10.86 (br s, 2H, NH), 7.00e6.20
(m, 12H, ArH), 5.09 (d, J¼13.4 Hz, 1H, ArCH2Ar, ax), 4.96
(d, J¼16.5 Hz, 2H, OCH2C(O)), 4.59 (d, J¼16.8 Hz, 2H,
OCH2C(O)), 4.42 (d, J¼13.7 Hz, 1H, ArCH2Ar, ax), 4.40 (d,
J¼13.9 Hz, 2H, ArCH2Ar, ax), 4.32e4.14 (m, 2H, OCH2),
4.06e3.89 (m, 4H, OCH2), 3.89e3.59 (m, 14H, OCH2),
3.28 (d, J¼14.0 Hz, 2H, ArCH2Ar, eq), 3.26 (d, J¼13.6 Hz,
1H, ArCH2Ar, eq), 3.22 (d, J¼13.8 Hz, 1H, ArCH2Ar, eq).
13C NMR: d 168.4 (C]O), 156.1, 155.9, 134.6, 134.6,
134.3, 133.5, 129.2, 128.8, 128.7, 128.3, 123.4, 122.8 (Ar),
120.5, 117.9 (CF3), 73.4 (OCH2 and OCH2C(O)), 70.9, 70.1,
70.0, 69.3 (OCH2), 31.2, 31.0, 30.6 (ArCH2Ar). Anal. Calcd
for C44H46O14N2S2F6: C, 52.59; H, 4.61; N, 2.79. Found: C,
52.28; H, 4.74; N, 2.66.
Acknowledgements
We thank the Division of Chemical Sciences, Geosciences,
and Biosciences of the Office of Basic Energy Sciences of the
U.S. Department of Energy (Grant DE-FG02-90ER14416) for
support of this research.
3.4. Procedure for competitive extraction of alkaline
earth metal cations
An aqueous solution of the alkaline earth metal chlorides
with hydroxides for pH adjustment (for 11 and 15, 0.10 M
HCl was utilized for pH adjustment) (2.0 mL, 10.0 mM in
each alkaline earth metal cation species) and 2.0 mL of
1.0 mM ligand in chloroform in a capped, polypropylene,
15-mL centrifuge tube was vortexed with a Glas-Col Multi-
Pulse Vortexer for 10 min at room temperature. The tube was
centrifuged for 10 min for phase separation with a Bectone
Dickinson Clay Adams BrandÒ Centrifuge. A 1.5-mL portion
of the organic phase was removed and added to 3.0 mL of
0.10 M HCl in a new, 15-mL, polypropylene centrifuge tube.
The tube was vortexed for 10 min and centrifuged for 10 min.
The alkaline earth metal cation concentrations in the aqueous
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