Comparison of upper and lower rim-functionalized, di-ionizable calix[4]arene-crown-6 structural isomers in divalent metal ion extraction

Article abstract of DOI:10.1016/j.tet.2012.07.103

Upper rim-functionalized, di-ionizable calix[4]arene-crown-6 ligands are synthesized and compared with structural isomers having the two acidic side arms attached to the lower rim. Solvent extractions of selected divalent metal cations (alkaline earth met

Full text of DOI:10.1016/j.tet.2012.07.103

Tetrahedron 68 (2012) 8789e8794
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Comparison of upper and lower rim-functionalized, di-ionizable calix[4]
arene-crown-6 structural isomers in divalent metal ion extraction
*
Amanda L. Boston, Eun Kyung Lee, Kazimierz Surowiec, Jerzy Gega, Richard A. Bartsch
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Upper rim-functionalized, di-ionizable calix[4]arene-crown-6 ligands are synthesized and compared
with structural isomers having the two acidic side arms attached to the lower rim. Solvent extractions of
selected divalent metal cations (alkaline earth metal cations, Pb2þ, and Hg2þ) from aqueous solutions
into chloroform by the upper and lower rim-functionalized, di-ionizable calix[4]arene-crown-6 isomers
are utilized to assess the effects of this structural modification on metal ion complexation abilities of the
ligands. The observed effects are compared with those reported for analogous di-ionizable calix[4]arene-
crown-5 structural isomers.
Received 12 July 2012
Accepted 31 July 2012
Available online 7 August 2012
Keywords:
Calixarenes
Crown ethers
Proton-ionizable groups
Metal ion extraction
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
variations upon metal ion extraction efficiency and selectivity for
substituted calix[4]arene-crown ether ligands in which the two
Calixarenes are a major category of building blocks for supra-
molecular chemistry research.1e4 Structures of these versatile
molecules are readily modified. A common structural variation is
connecting two of the phenolic oxygens on the lower rim with
a polyether chain to give a calixarene-crown ether (also called
calixcrown), such as 1 (Fig. 1).4
remaining phenolic oxygens are substituted with acidic side arms.
These structural features include the calixarene conformation
(cone, partial cone, 1,3-alternate, 1,2-alternate), crown ether ring
size, type of acidic group in the side arm, identification of donor
atoms in the crown ether ring, and attachment of lipophilic alkyl
groups on the upper rim.5e8 These ligands are designed for com-
plexation of divalent metal ions. Ionization of the ligand in the
extraction process provides the requisite anions for formation of an
electroneutral di-ionized ligandedivalent metal ion complex. This
markedly enhances the metal ion extraction efficiency when the
aqueous phase anion is hydrophilic chloride, nitrate, or sulfate. In
addition to carboxylic acid groups, N-(X)sulfonyl carboxamide
functionalities, eC(O)NHSO2X, have been employed. This type of
acidic moiety was first utilized in proton-ionizable lariat ethers for
alkali metal cation separations.9 It represents an important struc-
tural modification in that the NeH acidity can be ‘tuned’ by varying
the electron-withdrawing ability of X. Also the N-(X)sulfonyl car-
boxamidate anions formed by their ionization are softer10 than
carboxylate anions.
A frequently encountered application of calixarene and calix-
1
Fig. 1. Upper and lower rims of calix[4]arene-crown-n (n¼2e4) compounds in the
cone conformation.
In the most recent study, we investigated the effect of moving
the two acidic side arms from the lower rim of di-ionizable calix[4]
arene-crown-5 ligands to the upper rim (Fig. 2).11 Ligands 2 and 3
are structural isomers with two acidic side arms attached to the
lower rim in the former and to the upper rim in the latter. Metal ion
binding sites in ionized ligands 2 are the lower rim polyether ring
flanked by two ionized side arms and the aromatic nucleus of the
areneecrown ether compounds is metal ion separation by solvent
extraction from an aqueous phase into an organic phase. In earlier
studies, we have examined the effects of systematic structural
* Corresponding author. Tel.: þ1 806 742 3069; fax: þ1 806 742 1289; e-mail
calixarene scaffold in cationep interactions with soft metal
address: richard.bartsch@ttu.edu (R.A. Bartsch).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.103

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A.L. Boston et al. / Tetrahedron 68 (2012) 8789e8794
Y
a
b
c
d
e
-OH
-NHSO2Me
-NHSO2Ph
-NHSO2C6H4-4-NO2
-NHSO2CF3
2a-e
3a-e
Fig. 2. Di-ionizable calix[4]arene-crown-5 structural isomers in the cone conformation with two acidic side arms on the lower rim in 2aee and the upper rim in 3aee.
cations.12,13 Potential metal ion binding sites in ionized ligands 3
are the lower rim polyether ring, the ionized acidic groups on the
upper rim, and a ‘deep pocket’ in which the metal ion interacts with
form the organolithium intermediate, and then bubbling in CO2.
After protonation by aqueous HCl, the crude product was recrys-
tallized to give 5a in 38% yield. Di(carboxylic acid) 5a was refluxed
with oxalyl chloride in benzene to produce the corresponding
di(acid chloride). A commercially available sulfonamide was stirred
with NaH in THF. A solution of the di(acid chloride) in THF was
added to the sodium sulfonamidate mixture. Ligands 5bee were
obtained in modest 32e55% yields.
Conformational mobility is often observed in calix[4]arenes
containing lower rim methoxy groups.15 However, the NMR
spectra of calix[4]arene-crown-5 ligands 3aee revealed that
they were locked in the cone conformation.11 Examination of the
1H NMR, 13C NMR, and 1He13C heteronuclear correlation (HET-
COR) spectra for ligands 5aee reveals conformational mobility
based on the de Mendoza rule.16 For all five ligands, a 13C NMR
the pendent ionized groups and also has cationep interactions
with the aryl groups of the calixarene. Relocating the acidic side
arms was found to exert substantial effects on their divalent metal
ion extraction behavior.11 For the lower rim-functionalized ligand
series 2aee and upper rim-functionalized ligand series 3aee,
changes in selectivities and efficiencies were observed for different
divalent metal cation types, hard10 alkaline earth metal cations
(AEMC), intermediate Pb2þ, and soft Hg2þ
.
To gain further insight into how the location of the acidic side
arms affects the metal ion extraction behavior of such ligands, we
have now extended the comparison of comparison to di-ionizable
calix[4]arene-crown-6 structural isomers (Fig. 3). Earlier, we re-
ported results for AEMC extractions by lower rim-functionalized
crown-6 analogues 4aee (Fig. 3).14 We now describe the prepara-
tion of upper rim-functionalized structural isomers 5aee and their
solvent extractions of AEMC, Pb2þ, and Hg2þ. Also, we have ex-
panded the species examined in solvent extractions by the lower
signal at
bridge protons exhibiting a widely separated AX pattern in the
1H NMR spectra. A second signal at
35e36 ppm correlated with
d 30e31 ppm correlated to diastereotopic syn-ArCH2Ar
d
a singlet for the homotopic anti-ArCH2Ar bridge protons at
3.62 ppm. Substantial broadening consistent with less confor-
mational mobility was observed for di(carboxylic acid) 5a than
for 5bee.
rim-functionalized ligands 4aee to include Pb2þ and Hg2þ
.
Y
a
b
c
d
e
-OH
-NHSO2Me
-NHSO2Ph
-NHSO2C6H4-4-NO2
-NHSO2CF3
4a-e
5a-e
Fig. 3. Calix[4]arene-crown-6 structural isomers 4aee with two acidic side arms on the lower rim and 5aee with two acidic side arms on the upper rim.
2. Results and discussion
In addition to the NMR spectral results, new ligands 5aee were
characterized by IR spectroscopy and by combustion analysis.
2.1. Synthesis of upper rim-functionalized, di-ionizable calix
[4]arene-crown-6 ligands
2.2. Metal ion extractions by di-ionizable calix[4]arene-
crown-6 isomers 4aee and 5aee
Preparation of ligands 5aee with two acidic side arms on the
upper rim is summarized in Scheme 1. Refluxing a mixture of
dibrominated dimethoxycalix[4]arene 6,11 Cs2CO3, and penta-
ethylene glycol ditosylate14 in MeCN gave a 73% yield of dibromi-
nated dimethoxycalix[4]arene-crown-6 7. Di(carboxylic acid) 5a
was synthesized by dissolving 7 in THF at ꢀ78 ꢁC, adding BuLi to
Divalent metal ion extractions from aqueous solutions into
chloroform were utilized to probe the effect of moving the acidic
side arms from the lower rim in the previously reported12 crown-6
ligands 4aee to the upper rim in crown-6 ligands 5aee. Results
from competitive solvent extractions of AEMC (Mg2þ, Ca2þ, Sr2þ
,

A.L. Boston et al. / Tetrahedron 68 (2012) 8789e8794
8791
6
7
X
b
c
d
e
-Me
-Ph
-C6H4-4-NO2
-CF3
5a
5b-e
Scheme 1. Synthesis of calix[4]arene-crown-6 ligands 5aee with two acidic side arms on the upper rim. Reagents and conditions: (a) TsO(CH2CH2O)5Ts, Cs2CO3, MeCN, reflux; (b)
(i) BuLi, THF, ꢀ78 ꢁC; (ii) CO2; (c) (i) (COCl)2, C6H6, reflux; (ii) XSO2NH2, NaH, THF, rt.
(a)
(b)
(d)
(e)
(c)
and Ba2þ) by ligands 4aee were presented previously.17 We report
here the results for competitive solvent extractions of AEMC by li-
gands 5aee and single species extractions of Hg2þ and Pb2þ by li-
gands 4aee and 5aee. These solvent extractions included hard
100
80
60
40
20
0
AEMC, intermediate Pb2þ, and soft Hg2þ 10
.
2.2.1. Competitive solvent extraction of AEMC by di-ionizable calix[4]
arene-crown-6 ligands 4aee and 5aee. Competitive solvent ex-
tractions of aqueous AEMC solutions (2.00 mM in each) were
conducted with 1.00 mM solutions of ligands 4aee and 5aee in
chloroform. Plots of metal loadings of the organic phase versus the
equilibrium pH of the aqueous phase are shown in Figs. 4 and 5
(redrawn from the published data17), respectively.
All ligands 4aee reached 100% total metals loadings for for-
mation of 1:1 complexes and showed very good-to-excellent Ba2þ
selectivity. The high Ba2þ selectivity was attributed to the size fit of
this hard AEMC within the hard polyether cavity. Also, electrostatic
stabilization is provided by the ionized side arms on the lower rim,
one on each side of the polyether-complexed divalent metal ion.
Upper rim-functionalized ligands 5aed performed moderately
well in AEMC extractions. Ligand 5d gave the highest total metals
loading, reaching 86%. The ionizable group identity in the upper
rim-functionalized ligands 5aed is seen to affect the selectivity in
AEMC extractions. The Ca2þ selectivity observed with di(carboxylic
acid) 5a changed to modest extraction selectivity for Ba2þ when the
acidic function was N-(X)sulfonyl carboxamide in ligands 5bed.
The Ca2þ selectivity for 5a suggests greater participation of the hard
ionized groups in 5a. With 5bed, the softer ionized group sites on
the upper rim allow greater participation of the crown ether unit or
2
4
6
8 10 12 2
4
6
8 10 12
2
4 6 8 10 12 2 4 6 8 10 120 2 4 6 8 1012
pH
Fig. 4. Percent metal loading versus the equilibrium pH of the aqueous phase for
competitive solvent extraction of AEMC into chloroform by lower rim-functionalized,
di-ionizable calix[4]arene-crown-6 ligands 4aee: (a) 4a, (b) 4b, (c) 4c, (d) 4d, (e) 4e.
(,¼Mg2þ, B¼Ca2þ, 6¼Sr2þ
,
¼Ba2þ.)
7
extractant compared with 5aed, reaching only 12% of total metals
loading. In contrast, the previously examined14 lower rim-
functionalized analogue 4e gave better Ba2þ selectivity than those
observed with 4aed. The reason of the ineffectiveness of ligand 5e
as an AEMC extractant is not apparent at this time.
2.2.2. Single species solvent extraction of Pb2þ by di-ionizable calix[4]
arene-crown-6 ligands 4aee and 5aee. For solvent extraction of
aqueous Pb2þ (1.00 mM) solutions by 0.50 mM solutions of ligands
4aee and 5aee in chloroform, plots of Pb2þ loading of the organic
phase versus the equilibrium pH of the aqueous phase are shown in
the
p-electron rich cavity of the calix[4]arene unit.
Overall comparisons of AEMC extraction efficiency and selec-
tivities for lower rim-functionalized ligands 4aed with those upper
rim-functionalized ligands 5aed show the former to be more ef-
fective. Surprisingly, ligand 5e was found to be a very poor AEMC

8792
A.L. Boston et al. / Tetrahedron 68 (2012) 8789e8794
2.2.3. Single species solvent extraction of Hg2þ by di-ionizable calix
(a)
(b)
(d)
(e)
(c)
100
80
60
40
20
0
[4]arene-crown-6 ligands 4aee and 5aee. For single species solvent
extraction of aqueous Hg2þ solutions (0.25 mM) by 0.25 mM solu-
tions of di-ionizable ligands 4aee and 5aee in chloroform, plots of
metal loading of the organic phase versus the equilibrium pH of the
aqueous phase are presented in Fig. 7. Each panel compares the ex-
traction efficiencies for soft Hg2þ for a given acidic side arm attached
to the lower (open symbols) and upper (filled symbols) rims.
(a)
(b)
(d)
(e)
(c)
100
80
60
40
20
0
2
4
6
8 10 12 2
4
6
8 10 12
2
4 6 8 10 12 2 4 6 8 10 12 2 4 6 8 10 12
pH
Fig. 5. Percent metal loading versus the equilibrium pH of the aqueous phase for
competitive solvent extraction of alkaline earth metal cations into chloroform by upper
rim-functionalized, di-ionizable calix[4]arene-crown-6 ligands 5aee: (a) 5a, (b) 5b, (c)
5c, (d) 5d, (e) 5e. (,¼Mg2þ, B¼Ca2þ, 6¼Sr2þ
,
¼Ba2þ.)
7
Fig. 6. In this figure, each panel compares the extraction efficiency
toward intermediate Pb2þ for a given acidic side arm attached to
the lower (open symbols) and upper (filled symbols) rims.
0
2
4
6
0
2
4
6
0
2
4
6
0
2
4
6
0
2
4
6
pH
(a)
(b)
(d)
(e)
(c)
100
80
60
40
20
0
Fig. 7. Percent metal loading versus equilibrium pH of the aqueous phase for single
species solvent extraction of Hg2þ into chloroform by lower rim-functionalized, di-
ionizable calix[4]arene-crown-6 ligands 4aee and upper rim-functionalized, di-ion-
izable calix[4]arene-crown-6 ligands 5aee: (a) 4a and 5a, (b) 4b and 5b, (c) 4c and 5c,
(d) 4d and 5d, (e) 4e and 5e. (,¼4aee, -¼5aee.)
For the di-ionizable calix[4]arene-crown-6 ligands 4aee
and 5aee, the extraction efficiencies for soft Hg2þ were in the range
of 40e100%. Whether it is better to have the acidic side arms
attached to the lower or upper rim depended upon the acid group.
For di(carboxylic acid)s 4a and 5a, Hg2þ loading for the latter was
60%; whereas the metal loading for the former was only 40%. Thus
when the side arm contained a hard carboxylate anion, extraction
of soft Hg2þ was favored by having the acidic side arms on the
upper rim. With the N-(X)sulfonyl carboxamide ionizable groups,
the lower rim-functionalized ligands 4bee provided a 16e27%
higher metal loading than the 5bee analogues. For both series
4bee and 5bee, there was a stepwise increase in Hg2þ extraction as
X was varied in the order eMe<ePh<eC6H4e4-NO2<eCF3. This is
the order of increasing ligand acidity within each series. Ligands 4e
and 5e with the softest ionizable groups in the side arms were the
0
2 4 6 8 100 2 4 6 8 10 0 2 4 6 8 10 0 2 4 6 8 10 0 2 4 6 8 10
pH
Fig. 6. Percent metal loading versus equilibrium pH of the aqueous phase for single
species solvent extraction of Pb2þ into chloroform by lower rim-functionalized, di-
ionizable calix[4]arene-crown-6 ligands 4aee and upper rim-functionalized, di-ion-
izable calix[4]arene-crown-6 ligands 5aee: (a) 4a and 5a, (b) 4b and 5b, (c) 4c and 5c,
(d) 4d and 5d, (e) 4e and 5e. (,¼4aee, -¼5aee.)
most efficient extractants for soft Hg2þ
.
3. Conclusions
All lower rim-functionalized ligands 4aee showed very high
extraction efficiencies for Pb2þ with di(carboxylic acid) 4a being the
only ligand in this series to have a metal loading percentage below
100%.
In earlier investigations of systematic structural variations in di-
ionizable calix[4]arene-crown-5 ligand series 2aee and 3aee, two
acidic side arms were attached to the lower rim in 2aee and to the
upper rim in 3aee. In the present study, a new series of di-ionizable
calix[4]arene-crown-6 ligands 5aee with two acidic side arms on
the upper rim was prepared for comparison with the previously
reported, structurally isomeric crown-6 ligand series 4aee having
two acidic side arms on the lower rim. The objective was to com-
pare the divalent metal ion complexing properties of the crown-6
ligand series 4aee and 5aee to ascertain if it is better to have the
two acidic side arms attached to the lower or upper rim,
respectively. Another objective was to determine if the difference in
divalent metal ion complexing behavior for lower versus upper rim
attachment of the acidic side arms varies as the crown ether ring
Upper rim-functionalized ligands 5a and 5e were found to be
very good Pb2þ extractants with the latter reaching 100% metal
loading for formation of a 1:1 complex. On the other hand, ligands
5b and 5c were very poor Pb2þ extractants. Ligand 5d is a moder-
ately efficient extractant for Pb2þ, reaching 52% metal loading. For
ligands 5bee, electron withdrawal by X in the N-(X)sulfonyl car-
boxamide moiety affected Pb2þ extraction efficiency. The metal
loading for intermediate Pb2þ increased in the order X¼eMe,
ePh<eC6H4e4-NO2<eCF3 as the acidity of the upper rim side
arms was enhanced. This is also the order of increasing softness of
the ionized group.

A.L. Boston et al. / Tetrahedron 68 (2012) 8789e8794
8793
size in the di-ionizable calix[4]arene-crown ether is changed from
crown-5 to crown-6.
For these comparisons, the ionizable groups in the acidic side
arms were eCO2H and eC(O)NHSO2X, in which the acidity may be
‘tuned’ by varying the inductive effects of X.
IR100 FT-IR spectrometer as deposits from CH2Cl2 solutions on
NaCl plates. The absorptions are expressed in wavenumbers
(cmꢀ1). The 1H and 13C NMR spectra were recorded with a Varian
Unity INOVA 500 MHz FT-NMR (1H 500 MHz and 13C 126 MHz)
spectrometer at 296 K in CDCl3 with TMS as internal standard.
NMR spectra revealed that in contrast to the lower rim-
functionalized ligands 4aee, which were locked in the cone con-
formation, analogous upper rim-functionalized ligands 5aee were
conformationally mobile.
In competitive extraction of AEMC by di(carboxylic acid) 5a, there
was selectivity for hard Ca2þ suggesting dominant interaction with
the ionized groups on the upper rim. Ba2þ selectivity for softer N-(X)
sulfonyl carboxamide ligands 4bee and 5bee was consistent with
Chemical shifts (d) are given in parts per million (ppm) downfield
from TMS and coupling constant values (J) are given in hertz.
Combustion analysis was performed by Desert Analytics Labora-
tory (now Columbia Analytical Services) of Tucson, Arizona. For
compounds 5e and 6, the combustion analysis results indicated
the presence of small amounts of C6H6 and CH2Cl2, respectively.
This was verified by singlets at
d 7.36 and 5.32, respectively, in
their 1H NMR spectra.
enhanced metal ion-
p
-aryl or metal ion-polyether interaction. The
Reagents were purchased from commercial suppliers and used
directly unless otherwise noted. Acetonitrile (MeCN) was dried
over CaH2 and distilled immediately before use. Tetrahydrofuran
(THF) was dried over sodium with benzophenone as an indicator
and distilled immediately before use. Dibrominated dimethox-
ycalix[4]arene 611 and pentaethylene glycol ditosylate14 were pre-
pared according to literature procedures.
lower rim-functionalized ligands were more effective and selective
extractants for Ba2þ than their upper rim-functionalized analogues.
Comparison of these results for AEMC extractions by crown-6
ligands with those published for crown-5 analogues revealed for
the crown-6 ligands a greater benefit in having the acidic side arms
on the lower rim versus the upper rim.
For single species extractions of intermediate Pb2þ, high effi-
ciency was observed for all members of the lower rim-
functionalized series 4aee, but only for ligands 5a and 5e from
the upper rim-functionalized series. For upper rim-functionalized
ligands 5b and 5c, Pb2þ extraction was negligible. A modest level
of Pb2þ extraction was observed for ligand 5d. Thus, for the series
5bee with soft N-(X)sulfonyl carboxamide side arms attached to
the upper rim, Pb2þ extraction increased as X was varied in the
order eMe, ePh<eC6H4e4-NO2<eCF3.
These contrasting results between lower rim- and upper rim-
functionalization are very similar to the extraction behaviors
exhibited by lower rim-functionalized, di-ionized calix[4]arene-
crown-5 analogues 2aee and upper rim-functionalized crown-5
analogues 3aee.13 Ligands in series 2aee all exhibited high levels of
Pb2þ extraction. Ligands 3a and 3e were very good extractants for
Pb2þ, and very low loadings were observed for 3bed.
4.2. Synthesis of di(carboxylic acid) ligand 5a
4.2.1. 5,17-Dibromo-25,27-dimethoxycalix[4]arene-crown-6 (7). A
mixture of 6 (5.00 g, 8.20 mmol) and Cs2CO3 (6.65 g, 20.15 mmol)
in MeCN (600 mL) was stirred under nitrogen for 30 min. A so-
lution of pentaethylene glycol ditosylate (4.95 g, 9.00 mmol) in
MeCN (50 mL) was added dropwise over a 1-h period. The mixture
was refluxed for 24 h, the solvent was evaporated in vacuo, and
the residue was dissolved in CH2Cl2 (250 mL). The solution was
washed with 5% aqueous HCl (100 mL) and then H2O (2ꢂ250 mL).
The organic layer was dried over MgSO4. The solvent was evapo-
rated in vacuo to give a solid, which was chromatographed on
silica gel with hexaneseEtOAc (3:2) as eluent to obtain off-white
solid 7 (4.83 g, 73%) with mp 220e222 ꢁC. 1H NMR (500 MHz,
CDCl3):
d
3.06, 4.23 (AX, J¼12.5 Hz, 2H), 3.10 (s, 2H), 3.14, 4.40 (AX,
For soft Hg2þ, all lower rim-functionalized ligands 4bee con-
taining the N-(X)-sulfonyl carboxamide moiety were more efficient
in single species extractions than their upper rim analogues 5bee.
However, the upper rim-functionalized di(carboxylic acid) 5a was
a more effective extractant than 4a. Ligands 4e and 5e with the
softest ionized group were the most efficient Hg2þ extractants,
J¼12.5 Hz, 4H), 3.39e3.52 (m, 2H), 3.57 (s, 3H), 3.61 (s, 1H),
3.59e3.99 (m, 18H), 4.00 (s, 3H), 6.45 (s, 2H), 6.57 (s, 1H), 6.97 (t,
J¼7.5 Hz, 2H), 7.06 (d, J¼7.5 Hz, 1H), 7.10 (s, 1H), 7.14 (d, J¼7.5 Hz,
2H), 7.30 (d, J¼7.5 Hz, 1H), 7.27e7.33, 6.40e7.19 (m, 10H). 13C NMR
(126 MHz, CDCl3):
d 30.6, 35.9, 58.9, 60.8, 61.5, 70.5, 70.7, 70.8,
70.8, 71.0, 71.2, 71.3, 73.1, 74.2, 114.9, 115.3, 121.7, 122.6, 123.0,
128.9, 129.0, 131.2, 131.6, 133.1, 133.9, 135.8, 136.3, 154.7, 155.1,
159.1. Anal. Calcd for C40H44O8Br2$0.2CH2Cl2: C, 58.22; H 5.59.
Found: C, 58.22; H, 5.59.
suggesting maximal soft metal ionep aryl interactions.
Although crown-6 ligands 4aee and 5aee were found to exhibit
considerable similarity to those reported for crown-5 ligands 2aee
and 3aee in AEMC and Pb2þ extractions, the Hg2þ extractions
showed a marked ring size effect. For the crown-6 ligands, Hg2þ
extraction efficiency was higher for di(carboxylic) acids 4a and 5a
when the acidic side arms were attached to the upper rim. In contrast
for the crown-5 di(carboxylic) acids 2a and 3a, the Hg2þ extraction
levelwashigherwhen the acidic sidearms were onthelowerrim. For
the crown-6 N-(X)sulfonyl carboxamides, Hg2þ extraction by crown-
6 ligands 4bee and 5bee is favored when the acidic side arms are
attached to the lower rim. On the other hand for crown-5 N-(X)sul-
fonyl carboxamides 2bee and 3bee, the Hg2þ extraction level is
greater when the acidic side arms are on the upper rim.
4.2.2. 5,17-Bis(carboxy)-25,27-dimethoxycalix[4]arene-crown-6
(5a). To a solution of 7 (1.00 g, 1.23 mmol) in THF (50 mL) at ꢀ78 ꢁC
under nitrogen was added BuLi in hexanes (3.84 mL, 6.15 mmol,
M¼1.6). The solution was stirred for 1 h. Carbon dioxide was bub-
bled into the solution for 3 h and then the solution was stirred for
another 30 min. The mixture was allowed to warm to room tem-
perature and 5% aqueous HCl (10 mL) was added. The solvent was
evaporated in vacuo and the residue was dissolved in CH2Cl2. The
organic layer was washed with 6 N HCl and then with water. The
organic layer was dried over MgSO4. The solvent was evaporated in
vacuo. The solid residue was recrystallized from MeCN to obtain
white solid 5a (0.35 g, 38%), which decomposed at 278e280 ꢁC. IR
(deposit from CH2Cl2 solution on a NaCl plate): 3260 (OeH), 1690
Thus, expansion of the polyether ring in the calixcrown ligands
by a single ethyleneoxy unit is found to reverse the preferred acidic
side arm attachment sites in Hg2 extraction.
(C]O) cmꢀ1 1H NMR (500 MHz, CDCl3):
. d 3.07 (s, 1H), 3.10, 4.25
4. Experimental
4.1. General
(AX, J¼12.5 Hz, 2H), 3.18, 4.44 (AX, J¼12.5 Hz, 4H), 3.38e3.52 (m,
2H), 3.54e3.62 (m, 3H), 3.62e3.98 (m, 19H), 4.00 (s, 3H), 6.88e7.05
(m, 5H), 7.05e7.15 (m, 2H), 7.19 (d, J¼7.5 Hz, 1H), 7.32 (d, J¼7.5 Hz,
1H), 7.68 (s, 1H), 12.35e13.71 (br s, 2H). 13C NMR (126 MHz, CDCl3):
Melting points were determined with a Mel-Temp melting
point apparatus. Infrared (IR) spectra were recorded with a Nicolet
d
30.5, 35.6, 58.8, 60.6, 61.4, 70.4, 70.5, 70.7, 70.8, 70.9, 71.2, 71.3,
73.0, 74.0, 121.7, 122.9, 123.2, 128.9, 129.0, 129.6, 130.5, 130.9, 131.2,

8794
A.L. Boston et al. / Tetrahedron 68 (2012) 8789e8794
131.7,133.3,134.0,134.7,136.4,136.4, 158.2,160.0,160.5,172.1,172.6.
Anal. Calcd for C42H46O12: C, 67.71; H 6.12. Found: C, 67.91; H, 6.24.
to give white solid 5d (0.36 g, 53%) with mp 282e283 ꢁC. IR (deposit
from CH2Cl2 solution on a NaCl plate): 3266 (NH), 1699 (C]O),
1348, 1147 (SO2) cmꢀ1. 1H NMR (500 MHz, CDCl3):
d 3.08, 4.34 (AX,
4.3. General procedure for synthesis of 5,17-bis[N-(X)sulfonyl
carbamoylmethoxy]-25,27-dimethoxycalix[4]arene-crown-6
ligands 5bee
J¼12.5 Hz, 2H), 3.17 (s, 2H), 3.18, 4.44 (AX, J¼12.5 Hz, 4H),
3.29e3.81 (m, 17H), 3.81e4.02 (m, 6H), 4.05 (s, 3H), 6.80 (s, 2H),
6.82e7.03 (m, 3H), 7.08 (d, J¼7.5 Hz, 1H), 7.17 (d, J¼7.5 Hz, 2H),
7.28e7.34 (m, 2H), 8.17e8.51 (m, 8H), 9.01e9.20 (br s, 1H),
Di(carboxylic acid) 5a (0.50 g, 0.68 mmol) was dried with a ben-
zene azeotrope before addition of oxalyl chloride (0.58 mL,
6.75 mmol) in benzene (25 mL). The solution was refluxed for 6 h.
Formation of the di(acid chloride) was confirmed by an IR shift of the
C]O absorption from 1690 cmꢀ1 in 5a to 1747 cmꢀ1. The benzene
was evaporated in vacuo and the residue was dried under oil-pump
vacuumfor 30min. The sodium sulfonamidesalt wasprepared under
nitrogen by dropwise addition of the appropriate sulfonamide
(1.69 mmol) dissolved in THF (20 mL) to a mixture of NaH (0.16 g,
6.75 mmol) in THF (20 mL). This mixture was stirred for 2 h followed
by dropwise addition of the di(acid chloride) in THF (10 mL). The
mixture was stirred overnight (4 h for p-nitrobenzenesulfonamide)
at room temperature after which the solvent was evaporated in
vacuo. The residue was dissolved in CH2Cl2, and H2O (10 mL) was
carefully added. The organic layer was washed with 6 N HCl until
pH¼1 and dried over MgSO4. The solvent was evaporated in vacuo
and the crude product was purified by column chromatography.
9.55e9.77 (br s, 1H). 13C NMR (126 MHz, CDCl3):
d 30.7, 30.7, 36.1,
60.2, 61.3, 61.6, 70.4, 70.5, 70.7, 70.7, 70.8, 70.9, 71.1, 71.2, 73.4, 74.7,
122.3, 122.9, 123.4, 124.1, 124.2, 125.9, 126.1, 127.8, 128.4, 128.8,
129.2, 129.5, 130.2, 130.3, 123.1, 123.3, 133.6, 134.7, 135.5, 135.8,
136.1,144.0,144.2,150.6,150.7,157.5, 158.3, 159.0, 160.2, 161.1, 165.5,
166.4. Anal. Calcd for C54H54O18N4S2: C, 58.37; H, 4.90; N, 5.04.
Found: C, 58.45; H, 4.95; N, 5.07.
4.3.4. 5,17-Bis(N-trifluoromethanesulfonyl carbamoylmethoxy)-
25,27-dimethoxycalix[4]arene-crown-6 (5e). The crude product
was chromatographed on silica gel with EtOAcehexanes (4:1) as
eluent to give white solid 5e (0.30 g, 44%) with mp 224e226 ꢁC. IR
(deposit from CH2Cl2 solution on a NaCl plate): 3210 (NH), 1716
(C]O), 1390, 1135 (SO2) cmꢀ1 1H NMR (500 MHz, CDCl3):
. d 3.14,
4.38 (AX, J¼12.5 Hz, 2H), 3.18 (s, 2H), 3.25, 4.49 (AX, J¼12.5 Hz, 4H),
3.33e3.51 (m, 2H), 3.58 (s, 3H), 3.61e3.83 (m, 12H), 3.92 (s, 4H),
3.95e4.06 (m, 2H), 4.08 (s, 3H), 6.90 (s, 2H), 6.97 (s, 1H), 7.03
(t, J¼7.5 Hz, 2H), 7.14 (d, J¼7.5 Hz, 1H), 7.23 (d, J¼7.5 Hz, 2H), 7.34
(d, J¼7.5 Hz, 1H), 7.34 (s, 1H). 13C NMR (126 MHz, CDCl3):
d 30.9,
4.3.1. 5,17-Bis(N-methanesulfonyl carbamoylmethoxy)-25,27-
dimethoxycalix[4]arene-crown-6 (5b). The crude product was
recrystallized from MeCN to give 0.18 g of recovered 5a and a residue,
which was chromatographed on silica gel with CH2Cl2eMeOH (50:1)
as eluent and then a second column with EtOAcehexanes (4:1) as
eluent to give off-white solid 5b (0.12 g, 50%, accounting for re-
covered starting material) with mp 295e297 ꢁC. IR (deposit from
CH2Cl2 solution on a NaCl plate): 3181 (NH), 1688 (C]O), 1345, 1146
31.0, 36.4, 59.8, 61.5, 61.9, 70.7, 70.8, 70.9, 71.0, 71.0, 71.2, 71.4, 71.5,
73.7, 75.0, 115.5, 115.6, 118.1, 118.2, 120.6, 120.8, 122.6, 123.2, 123.3,
123.6, 124.0, 125.0, 125.3, 129.2, 129.6, 129.8, 132.1, 132.8, 134.1,
135.4, 136.0, 136.1, 158.0, 158.3, 159.1, 161.3, 162.0. Anal. Calcd
for C44H46F6O14N2S2$1.5C6H6: C, 56.73; H, 4.94; N, 2.50. Found: C,
56.94; H, 4.55; N, 2.59.
(SO2) cmꢀ1. 1H NMR (500 MHz, CDCl3):
2H), 3.15 (s, 6H), 3.19 (s,1H), 3.22, 4.47 (AX, J¼12.5 Hz, 4H), 3.39e3.85
(m, 17H), 3.91 (s, 5H), 3.96e4.06 (m, 2H), 4.09 (s, 3H), 6.71e7.44 (m,
10H), 8.93e9.20 (br s, 1H), 9.20e9.37 (br s, 1H). 13C NMR (126 MHz,
d
3.13, 4.36 (AX, J¼12.5 Hz,
4.4. Solvent extraction procedures
Competitive solvent extraction AEMC, single species extraction
of Hg2þ, and single species extraction of Pb2þ into chloroform were
performed as previously described.11
CDCl3):
d 30.6, 30.8, 36.1, 41.2, 41.4, 59.9, 61.2, 61.5, 70.5, 70.7, 70.8,
70.8, 70.9, 71.2, 73.3, 74.7,122.1,1231,123.6,126.0,126.5,127.8,128.6,
129.2, 129.4,131.8,132.6,133.5,134.6,135.3,136.1, 136.2,158.2,158.9,
160.1, 160.8, 166.5, 166.9. Anal. Calcd for C44H52O14N2S2: C, 58.91; H,
5.84; N, 3.12. Found: C, 58.79; H, 5.97; N, 2.85.
Acknowledgements
We thank the Division of Chemical Sciences, Geosciences, and
Biosciences of the Office of Basic Energy Sciences of the U.S. De-
partment of Energy (grant DE-FG02-90ER1445) for support of this
research.
4.3.2. 5,17-Bis(N-benzenesulfonyl carbamoylmethoxy)-25,27-
dimethoxycalix[4]arene-crown-6 (5c). The crude product was
chromatographed on silica gel with CH2Cl2eMeOH (100:1) as elu-
ent and then a second column with EtOAcehexanes (4:1) as eluent
to give white solid 5c (0.22 g, 32%) with mp 267e270 ꢁC. IR (deposit
from CH2Cl2 solution on a NaCl plate): 3256 (NH), 1696 (C]O),
References and notes
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2. Gutsche, C. D.; Muthukrishnan, R. J. Org. Chem. 1978, 43, 4905.
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1350, 1148 (SO2) cmꢀ1. 1H NMR (500 MHz, CDCl3):
d 3.08, 4.31 (AX,
J¼12.5 Hz, 2H), 3.19, 4.43 (AX, J¼12.5 Hz, 4H), 3.21 (s, 2H),
3.37e3.56 (m, 2H), 3.57 (s, 3H), 3.60e4.02 (m, 18H), 4.07 (s, 3H),
6.83 (s, 2H), 6.91 (s, 1H), 6.97 (t, J¼7.5 Hz, 2H), 7.08 (d, J¼7.5 Hz, 1H),
7.17 (d, J¼7.5 Hz, 2H), 7.27 (s, 1H), 7.33 (d, J¼7.5 Hz, 1H), 7.50 (t,
J¼7.5 Hz, 2H), 7.54e7.64 (m, 4H), 8.07 (d, J¼7.5 Hz, 2H), 8.13 (d,
J¼7.5 Hz, 2H), 9.04e9.49 (br s, 1H), 9.64e9.99 (br s, 1H). 13C NMR
7. Yang, Y.; Cao, X.; Surowiec, K.; Bartsch, R. A. J. Inclusion Phenom. Macrocyclic
Chem. 2010, 66, 163.
8. Tu, C.; Surowiec, K.; Bartsch, R. A. Tetrahedron 2007, 63, 4184.
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10. Jolly, W. L. Modern Inorganic Chemistry; McGraw-Hill: New York, NY,1984; p 208.
11. Yang, Y.; Arora, G.; Fernandez, F. A.; Crawford, J. D.; Surowiec, K.; Lee, E. K.;
Bartsch, R. A. Tetrahedron 2011, 67, 1389.
(126 MHz, CDCl3): d 30.8, 36.3, 60.3, 61.2, 61.4, 70.5, 70.6, 70.7, 70.8,
70.8, 70.9, 71.5, 71.2, 73.3, 74.7, 122.1, 123.3, 123.6, 126.7, 126.8,
128.0, 128.4, 128.7, 128.8, 128.9, 129.2, 129.5, 132.0, 132.5, 133.4,
133.9, 134.3, 135.2, 135.6, 135.9, 128.8, 138.9, 157.6, 158.2, 158.8,
159.8, 160.6, 165.4, 166.2. Anal. Calcd for C54H56O14N2S2: C, 63.51; H,
5.53; N, 2.74. Found: C, 63.49; H, 5.62; N, 2.52.
12. Ma, J. C.; Dougherty, D. A. Chem. Rev. 1997, 97, 1303.
ꢀ
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56, 3372.
4.3.3. 5,17-Bis(N-p-nitrobenzenesulfonyl carbamoylmethoxy)-25,27-
dimethoxycalix[4]arene-crown-6 (5d). The crude product was
chromatographed on silica gel with EtOAcehexanes (4:1) as eluent