New di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands: Synthesis and divalent metal ion extraction

Article abstract of DOI:10.1016/j.tet.2012.09.065

New di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands with elongated side arms in cone, partial-cone, and 1,2-alternate conformations of the calixarene scaffold are prepared and characterized. The acidic groups on the side arms include carboxylic acid and N-(X)sulfonyl carboxamide with X variation of -Me, -Ph, -C₆H₄-4-NO₂, and -CF₃. Solvent extractions of alkaline earth metal cations, Hg ²⁺, and Pb²⁺ from aqueous solutions into chloroform are employed to probe the effects of these structural modifications on the divalent metal ion complexation behavior of the new ligands.

Full text of DOI:10.1016/j.tet.2012.09.065

Tetrahedron 68 (2012) 10241e10251
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands: synthesis
and divalent metal ion extraction
,
,
,
,b
Amanda L. Boston a b, Eun Kyung Lee a b, Jennifer D. Crawford a b, Robert E. Hanes, Jr. a
,
,b,
Richard A. Bartsch a
*
a Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
b Beacon Sciences LLC, 11412 FM 2244 #110, Austin, TX 78738, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 August 2012
Received in revised form 8 September 2012
Accepted 11 September 2012
Available online 28 September 2012
New di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands with elongated side arms in cone,
partial-cone, and 1,2-alternate conformations of the calixarene scaffold are prepared and characterized.
The acidic groups on the side arms include carboxylic acid and N-(X)sulfonyl carboxamide with X
variation of eMe, ePh, eC6H4e4-NO2, and eCF3. Solvent extractions of alkaline earth metal cations,
Hg2þ, and Pb2þ from aqueous solutions into chloroform are employed to probe the effects of these
structural modifications on the divalent metal ion complexation behavior of the new ligands.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Calixarenes
Crown ethers
Calixcrowns
Proton-ionizable side arms
Metal ion extraction
1. Introduction
crown ethers possessed only poor metal cation binding abilities
with little selectivity.6e8
Calixarenes and crown ethers are both well-known building
blocks for the construction of selective metal ion receptors and
carriers.1,2 Of the former class of macrocyclic, multidentate ligands,
tetrameric calix[4]arene is particularly well-suited for this purpose
because of its accessibility, ease of chemical modification, and
cation binding properties. Incorporation of a polyether loop on the
lower rim of calix[4]arene not only enhances the cation binding
ability of the parent calixarene, but allows for selectivity control
through modulation of the crown ether ring size. These hybrid
receptors are identified as calixarene-crown ethers or calixcrowns.
Two types of polyether bridges on the lower rim of a calix[4]
arene molecule are possible: 1,3-bridging of distal phenolic units
and 1,2-bridging of proximal phenolic units.3 Until recently, studies
of calix[4]arene-crown ether compounds have been focused on
dialkylated, 1,3-bridged calix[4]arene-crown ethers. Ligands of this
type were found to exhibit high binding affinites and selectivities in
extractions of alkali and alkaline earth metal cations.4,5 Much less is
known about the properties of regioisomeric 1,2-bridged calix[4]
arene-crown ethers, which are more difficult to synthesize. Also,
initial investigations suggested that 1,2-bridged calix[4]arene-
Of particular interest in our metal ion separations research
program are calix[4]arene-crown compounds with two acidic side
arms attached to the remaining phenolic oxygens. Such ligands are
designed to effectively extract divalent metal ions from aqueous
solutions into organic diluents.9 Extraction proceeds by an ion-
exchange mechanism to form an electroneutral di-ionized cal-
ixcrown-divalent metal ion complex in the organic phase. This
avoids the need for concomitant transfer of a hydrophilic anion
from the aqueous phase.
The first example of a di-ionizable calixcrown compound was
the cone p-tert-butylcalix[4]arene-1,3-crown-5 di(carboxylic acid)
1 (Fig. 1) reported by Ungaro and Pochini in 1984.4
Recently, we undertook the synthesis of cone di-ionizable p-
tert-butylcalix[4]arene-1,2-crown ether ligands 2 (Fig. 2) and their
evaluation in divalent metal ion extractions from aqueous solutions
into chloroform.10e14 For this series of ligands, the polyether ring
was varied from crown-3 (m¼0)10,15 to crown-4 (m¼1)11,12 to
crown-5 (m¼2)13 to crown-6 (m¼3).14 For each polyether ring size,
the ionizable groups included both carboxylic acid and N-(X)sul-
fonyl carboxamides for which the acidity can be tuned by variation
of the electron-withdrawing ability of X.16 Surprisingly, di-ionizable
p-tert-butylcalix[4]arene-1,2-crown-4 ether ligands were found to
be very effective in competitive alkaline earth metal cation (AEMC)
* Corresponding author. Tel.: þ1 806 742 3069; fax: þ1 806 742 1289; e-mail
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.2012.09.065

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A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
the carbonyl group in the proton-ionizable function have been
examined in these investigations. The effect of elongating the side
arms by increasing the number of methylene groups in the spacer is
now explored.
2. Results and discussion
2.1. Geometry optimization of di-ionized calix[4]arene-1,2-
crown-4 barium complex
So far, we have been unsuccessful in preparing suitable crystals
for solid-state structure determination of a di-ionized p-tert-
butylcalix[4]arene-1,2-crown-4 complex with Ba2þ. To gain insight
into the structure of such a complex, the optimized geometry of
complex 5 (Fig. 3) was calculated. The ab initio calculations were
performed using the Gaussian 03 Revision D.01 suite of programs.17
For simplification, the four p-tert-butyl groups were truncated. The
ionizable side arms are eOCH2C(O)NHSO2CH3, which has a single
methylene group spacer.
1
Fig. 1. First reported di-ionizable calix[4]arene-crown ether 1.
The skeleton 3 was assembled using the GausView 4 program,
then minimized by semi-empirical methods with the AM1 basis
set. The barium complexes were solved using HartreeeFock theory
with custom basis sets: 6-31G-d,p for the atoms C, H, N, O, S;
LANL2DZ for barium complex 5; and LANL2MB for barium complex
4.18e20 LANL2MB treats first row elements with the STO-3G basis
set, and was chosen for complex 4, as it required less computational
resources, but demonstrated a geometry optimized structure con-
verged with the large number of atoms and a heavy atom, Ba. The
LANL2DZ (LANL2MB) basis set utilizes effective core potentials
(ECPs) for electrons near the nucleus and incorporates relativistic
effects important for heavy atoms. Complex 5 was prepared elec-
trically neutral with nitrogen of the ionized N-(methyl)sulfonyl
Y
a -OH
b -NHSO2Me
c -NHSO2Ph
d -NHSO2C6H4-4-NO2
e -NHSO2CF3
2a-e
Fig. 2. Di-ionizable p-tert-butylcalix[4]arene-1,2-crown ether ligands.
3
4
5
Fig. 3. Structures utilized in geometry optimization of barium complex 5.
extractions with extraordinarily high selectivity for Ba2þ. Since the
crown-4 ring is too small to accommodate Ba2þ, we envisioned an
extraction complex in which the large divalent metal ion perches
on the four polyether oxygens with the two ionized side arms co-
ordinating from the opposite side. The Ba2þ selectivity in compet-
itive AEMC extraction was found to be lower for analogues with the
larger polyether rings of crown-5 and crown-6 and nearly dis-
appeared with smaller crown-3 rings.
carboxamide function formally negative while the barium was
formally þ2.
The calculated structure for complex 5 is presented in Fig. 4. As
can be seen, Ba2þ is associated with the two ionized side arms.
There is some distance between the four crown ether oxygens and
the metal ion. From this calculated structure, the effect of elon-
gating the proton-ionizable side arms remains uncertain.
In further probing of the reason(s) for the unanticipated selec-
tivity for Ba2þ extraction observed with the p-tert-butylcalix[4]
arene-1,2-crown-4 ligands, the effect of replacing the four p-tert-
butyl groups on the upper rim with hydrogens was explored.12 This
variation in ligand structure produced some further enhancement
in the high selectivity for Ba2þ extraction.
2.2. Synthesis of di-ionizable p-tert-butylcalix[4]arene-1,2-
crown-4 compounds with elongated acidic side arms
Since side arms of the type eOCH2CH2C(O)Y can undergo
retro-Michael cleavage reactions under basic conditions, side arm
elongation to include two methylene groups in the spacer was not
a viable structural variation. Attention was focused on side arms
of eO(CH2)3C(O)Y and eO(CH2)4C(O)Y.
To date, only functional side arms of the type eOCH2C(O)Y with
a single methylene group spacer between the phenolic oxygen and

A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
10243
Reaction of calix[4]arene (6) with triethylene glycol ditosylate22
and 10 equiv of Cs2CO3 in MeCN gave the desired p-tert-butylcalix
[4]arene-1,2-crown (7) in 39% yield. Diesters 8 and 9 were syn-
thesized in 57 and 52% yields, respectively, by adding either ethyl
bromobutyrate or ethyl bromovalerate to a refluxing mixture of
calixcrown 7 and NaH in THF. Diesters 8 and 9 were hydrolyzed by
refluxing with 10% aqueous NMe4OH in THF to give the corre-
sponding di(carboxylic acid)s 10a and 11a in quantitative yields.
Di(carboxylic acid)s 10a and 11a were stirred at room temperature
in benzene with oxalyl chloride. The crude di(acid chloride) in THF
was added to a mixture of the appropriate sulfonamide and NaH in
THF. The N-(X)sulfonyl carboxamides 10bee and 11bee were ob-
tained in 72e95% yield. Ligands 10d, 10e, 11b, 11d, and 11e were
isolated as the monosodium salts. Further attempts to protonate
the monosodium salts resulted in cleavage of the N-(X)sulfonyl
carboxamide functionality.
Cone conformations of diesters 8 and 9, di(carboxylic acid)s 10a
and 11a, and N-(X)sulfonyl carboxamides 10bee and 11bee were
confirmed by 1H, 13C, 1He1H correlation (COSY), and 1He13C het-
eronuclear correlation (HETCOR) NMR spectroscopy. According to
the de Mendoza rule,23 the absence of peaks corresponding to the
bridging methylene carbons in the 13C NMR spectra at
w35e40 ppm shows that all four aryl units are syn to one another,
thus verifying the cone conformation. The syn arrangement of the
aryl groups in the cone conformation makes the axial and equatorial
protons diastereotopic to one another. These methylene protons
exhibit a classical AX pattern as widely separated doublets.24
The HETCOR spectra for 10aee and 11aee in the cone confor-
mation show a correlation between the bridging methylene car-
bons and bridging methylene protons (see Supplementary data).
These protons correlate with three different types of carbons,
proving that the crown ether moiety and the ionizable pendant
Fig. 4. Geometry optimized structure of barium complex 5.
2.2.1. Cone di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 li-
gands. Synthetic routes to cone di-ionizable p-tert-butylcalix[4]
arene-1,2-crown-4 ligands 10aee and 11aee with eO(CH2)3C(O)Y
and eO(CH2)4C(O)Y side arms, respectively, are presented in
Scheme 1. Preparation of p-tert-butylcalix[4]arene-1,2-crown-4 (7)
was initially attempted following a literature procedure.21 We ex-
perienced erratic results and yields from this reported procedure
and developed an alternative method for synthesis of calixcrown 7.
6
7
8 n=3
9 n=4
X
b -Me
c -Ph
d -C6H4-4-NO2
e -CF3
10a n=3
11a n=4
10b-e n=3
11b-e n=4
Scheme 1. Synthesis of di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands 10aee and 11aee in the cone conformation. Reagents and conditions: (a) TsO(CH2CH2O)3Ts,
Cs2CO3, MeCN, reflux; (b) Br(CH2)nCO2Et (n¼3 or 4), NaH, THF, reflux; (c) 10% aq NMe4OH, THF, reflux; (d) (i) (COCl)2, C6H6, rt; (ii) XSO2NH2, NaH, THF, rt.

10244
A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
arms are attached to their respective phenolic oxygens in proximal
positions (The presence of three different types of carbons is con-
sistent with the cone conformation.).
1,2-alternate conformer (Of the four limiting conformations for calix
[4]arene compounds, the 1,2-alternate conformation is the least
common.).25 Nevertheless, we discovered that the three conformers
in the diester mixture could be separated easily by column chro-
matography. This provided the synthetic route by which partial-
cone and 1,2-alternate analogues of cone ligands 10aee and
11aee were realized (Scheme 2).
2.2.2. Partial-cone and 1,2-alternate di-ionizable p-tert-butylcalix[4]
arene-1,2-crown-4 ligands. We sought to identify new conditions
whereby alkylation of p-tert-butylcalix[4]arene-1,2-crown-4 (7)
8 n=3
9 n=4
14 n=3
7
12 n=3
15 n=4
13 n=4
18a n=3
19a n=4
16a n=3
17a n=4
X
b -Me
c -Ph
d -C6H4-4-NO2
e -CF3
18b-e n=3
19b-e n=4
16b-e n=3
17b-e n=4
Scheme 2. Synthesis of partial-cone and 1,2-alternate di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 compounds 16aee, 17aee, 18aee, and 19aee. Reagents and conditions: (a)
Br(CH2)nCO2Et (n¼3 or 4), Cs2CO3, MeCN, reflux; (b) 10% aq NMe4OH, THF, reflux; (c) (i) (COCl)2, C6H6, rt; (ii) XSO2NH2, NaH, THF, rt.
would give a single non-cone conformer of the diester intermediate.
Several attempts gave crude products that contained mixtures of
the cone and partial-cone diesters, as well as the rarely encountered
Reaction of 7, Cs2CO3, and ethyl bromobutyrate in MeCN at
reflux gave a mixture of cone diester 8, partial-cone diester 12, and
1,2-alternate diester 14. The three regioisomers were separated by

A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
10245
column chromatography. Use of ethyl bromovalerate in place of
ethyl bromobutyrate produced a mixture of cone diester 9, partial-
cone diester 13, and 1,2-alternate diester 15 that was separated by
column chromatography.
10aee and 11aee in the cone conformation (9.58e12.28 ppm). This
is due to the deshielding effect that syn-arranged aryl groups have
on adjacent substituents.
Compounds 18aee and 19aee exhibit similar patterns and cor-
relations in their respective portions of their COSY and HETCOR
NMR spectra (see Supplementary data). The spectra further confirm
that these ligands are in the 1,2-alternate conformation. The
methylene protons correlate with three different types of carbons in
the HETCOR spectra, which verifies these compounds are in the 1,2-
alternate conformation, there is some symmetry present in these
compounds, and the crown ether rings are attached in a proximal
fashion.
Diesters 12e15 in the partial-cone and 1,2-alternate conforma-
tions were refluxed with Me4NOH in aqueous THF to give the de-
sired di(carboxylic acid)s 16a, 17a, 18a, and 19a in near-quantitative
yields. Each di(carboxylic acid) was stirred with oxalyl chloride in
benzene at room temperature to produce the crude di(acid chlo-
ride). The di(acid chloride) in THF was added to a mixture of the
appropriate sulfonamide and NaH in THF. The partial-cone N-(X)
sulfonyl carboxamides 16bee and 17bee with eO(CH2)3C(O)Y and
eO(CH2)4C(O)Y side arms, respectively, were realized in 39e99%
yield. The 1,2-alternate N-(X)sulfonyl carboxamides ligands 18bee
and 19bee with eO(CH2)4C(O)Y and eO(CH2)4C(O)Y side arms,
respectively, were obtained in 69e95%.yield.
2.3. Effects of acidic side arm elongation and calixarene unit
conformation on divalent metal ion extraction
Diesters 12e15, di(carboxylic acid)s 16a, 17a, 18a, and 19a, and N-
(X)sulfonyl carboxamides 16bee, 17bee, 18bee, and 19bee were
For comparison with the previously reported11,12 cone di-
ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands 2aee hav-
ing eOCH2C(O)Y side arms, solvent extractions of selected divalent
metal ion species from aqueous solutions into chloroform were
conducted. These included competitive extractions of hard AEMC
1
analyzed by H, 13C, COSY, and HETCOR NMR spectroscopy to verify
that they were the desired products in the appropriate conformations.
In the 1H NMR spectra for partial-cone 16bee and 17bee, the
NH protons appear as widely separated singlets. The downfield
singlet at 10.55e11.36 ppm corresponds to the proton on the syn-
arranged side arm and the more upfield singlet at 8.36e9.35 ppm
corresponds to the anti-arranged side arm. The three syn aryl units
of a partial-cone conformer create a ‘deshielding’ effect that shifts
a proton attached to these groups farther downfield compared to
those attached to the anti aryl unit.
(Mg2þ, Ca2þ, Sr2þ, and Ba2þ 11
termediate Pb2þ and soft Hg2þ 12
)
and single species extractions of in-
Recall that ligands 2aee with m¼1
.
showed high Ba2þ selectivity over other AEMC with near 100% metal
loadings. These ligands also showed high Pb2þ and Hg2þ extraction
propensities in single species extractions.12 They extracted >90% of
these metal ions except for di(carboxylic acid) 2a, which gave only
about 50% loading with Hg2þ
.
The bridging methylene protons adjacent to syn-arranged aryl
groups are also diastereotopic, each containing non-equivalent
axial and equatorial protons. AX patterns of two widely separated
doublets were observed in the 1H NMR spectrum for the bridging
methylene protons adjacent to syn aryl units.24 AB patterns or
singlet peaks were also observed for the methylene protons adja-
cent to anti-arranged aryl groups. As expected for compounds in
the partial-cone conformation, peaks at 35e40 ppm (anti) and
30e31 ppm (syn) corresponding to the bridging methylene carbons
were observed in the 13C NMR spectra.
Correlations of the bridging methylene groups in partial-cone li-
gands 16aee and 17aee exhibited similar patterns and correlations
in their respective 1H and 13C NMR spectra (see Supplementary data).
The peaks for the correlated methylene protons in their 1H NMR
spectra integrated with a 1:1:2 ratio. These three peaks represent the
syn-arranged aryl groups and the protons adjacent to the anti-
arranged groups. In the HETCOR spectra, these methylene protons
correlate with four different types of carbons, which verify that these
compounds are in the partial-cone conformation and contain no
symmetry due to the proximal attachment of the crown ether ring.
Compounds 18aee and 19aee in the 1,2-alternate conformation
exhibited at least two pairs of doublets in their 1H NMR spectra
corresponding to the bridging methylene protons. The two pairs of
doublets that always appear are widely separated (AX pattern), and
the other methylene protons either appear as a closely spaced AB
pattern or a singlet.24 These correspond to the protons adjacent to
syn aryl groups and anti aryl groups, respectively, and had an in-
tegration ratio of 1:1:2.
The extraction procedures were the same as those reported
previously10e14 with the following exception. Since ligands 10d,
10e, 11b, 11d, and 11e were obtained as monosodium salts, a mod-
ified procedure was employed to ensure removal the Naþ prior to
performing the extractions.
2.3.1. Solvent extraction of AEMC by di-ionizable p-tert-butylcalix[4]
arene-1,2-crown-4 ligands. Competitive solvent extraction of aque-
ous AEMC solutions (2.00 mM in Mg2þ, Ca2þ, Sr2þ, and Ba2þ) by
1.00 mM solutions of di-ionizable ligands 10aee,11aee,16aee,17aee,
18aee, and19aee in chloroformwas performed. Plots of metal loading
of the organic phase versus the equilibrium pH of the aqueous phase
are shown in Fig. S7 for cone ligands 10aee with eO(CH2)3C(O)Y side
arms and in Fig. S8 for cone ligands 11aee with eO(CH2)4C(O)Y side
arms. Immediately apparent is the poor extraction efficiency of these
10 ligands for AEMC. The highest metal cation loading of about 50%
was observed with di(carboxylic acid) ligand 10a. Only di(carboxylic
acid) ligands 10a and 11a show significant selectivity, in this case for
Ca2þ. Thus extending the eOCH2C(O)Y side arms of ligands 2aee
(n¼1) to eO(CH2)3C(O)Y in 10aee and eO(CH2)4C(O)Y in 11aee de-
stroys the efficient and selective extraction of Ba2þ
.
Changing the calixarene conformation in the calix[4]arene-1,2-
crown-4 ligand from cone to partial-cone or 1,2-alternate varies
the spatial relationship between the ionized side arms and the
crown-4 ring. For partial-cone ligands 16aee and 17aee, one side
arm is positioned near to the polyether ring and the other side arm
is remote. For the unusual 1,2-alternate conformation in ligands
18aee and 19aee, both acidic side arms are directed away from the
crown-4 ring.
Plots of metal loading of the organic phase versus the equilibrium
pH of the aqueous phase are shown in Fig. S9 for partial-cone ligands
16aee with eO(CH2)3C(O)Y side arms and in Fig. S10 for partial-
cone ligands 17aee with eO(CH2)3C(O)Y side arms. Ligands 16aee
are poor AEMC extractants. When the acidic side arms are length-
ened by one methylene group, the AEMC extraction efficiencies
improve somewhat for ligands 17b and 17c, with Ba2þ selectivity.
Plots of metal loading of the organic phase versus the equilib-
rium pH of the aqueous phase are shown in Fig. 5 for 1,2-alternate
Bridging methylene carbon peaks typically appear at 35e40 and
30e31 ppm in the 13C NMR spectrum corresponding to the carbon
atoms attached to anti and syn aromatic units, respectively.23 It was
found that the carbon atoms adjacent to syn aryl groups appear at
28e29 ppm for these compounds. Selected chemical shifts and
splitting patterns are presented in Table S1 in Supplementary data.
The NH protons attached to side arms on aryl groups syn to each
other but anti to the groups containing the 1,2-crown-4 moiety
exhibit peaks that appear as singlets. These singlets were relatively
upfield (9.17e10.04 ppm) compared to the NH protons in ligands

10246
A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
ligands 18aee with eO(CH2)3C(O)Y side arms and in Fig. 6 for 1,2-
alternate ligands 19aee with eO(CH2)4C(O)Y side arms. Ligands
18aee are found to be weak and unselective AEMC extractants.
When the acid side arms are lengthened by one methylene group,
we were surprised by the dramatic change in AEMC extraction
behavior. Ligands 19aed in the 1,2-alternate conformation with
eO(CH2)4C(O)Y side arms showed the highest AEMC loadings of the
six ligand series examined in this study. In comparison, cone 11c
and partial-cone 17c, the ‘second best’ in the six-ligand series,
reached maximum loadings of only 40%. The sharp contrast of
metals loading for the 1,2-alternate conformers over those exhibi-
ted by the cone and partial-cone conformers suggests that AEMC
coordination is optimized when the ionized extended side arms are
bearing side arms. When the ionized side arm contains N-(X)sulfonyl
carboxamide groups in 19bed, the extraction selectivity changes to
Ba2þ, the softest AEMC in the series.
2.3.2. Solvent extraction of Pb2þ by di-ionizable p-tert-butylcalix[4]
arene-1,2-crown-4 ligands. In 2007, results for solvent extraction of
intermediate Pb2þ from aqueous solutions into chloroform by cone
ligands 2bee (with m¼1) with short eOCH2C(O)NHSO2X side arms
were reported.12 In those single species extractions, Pb2þ loadings
were very high and exceeded 90% in all cases. The same result was
observed for the di(carboxylic acid) ligand 2a.
From solvent extraction of aqueous Pb2þ (1.00 mM) solutions by
0.50 mM chloroformsolutions of ligands 10aee,11aee,16aee,17aee,
18aee, and 19aee, plots of Pb2þ loading of the organic phase versus
theequilibrium pHof the aqueous phasearepresented in Figs. 7 and 8.
spatially close to one another and also to the
aromatic rings.
p-electron cloud of the
100
a)
b)
c)
a)
b)
d)
e)
c)
100
80
60
40
20
0
80
60
40
20
0
0
2
4
6
8
0
2
4
6
8
0
2
4
6
8
0
2
4
6
8 10120 2
4
6
8 10120 2 4 6 8 10120 2 4 6 8 10120 2 4 6 8 1012
pH
pH
pH
pH
Fig. 5. Percent metal loading versus the equilibrium pH of the aqueous phase for
competitive solvent extraction of AEMC into chloroform by 1,2-alternate, di-ionizable
calix[4]arene-1,2-crown-4 ligands 18aee with eO(CH2)3C(O)Y side arms. (a) 18a, (b)
Fig. 7. Percent metal loading versus the equilibrium pH of the aqueous phase for single
species solvent extraction of Pb2þ into chloroform by di-ionizable calix[4]arene-1,2-
crown-4 ligands in three conformations: (a) cone, 10aee , (b) partial-cone, 16aee,
and (c) 1,2-alternate, 18aee (,¼eCO2H; B¼eC(O)NHSO2CH3; 6¼eC(O)NHSO2C6H5;
¼eC(O)NHSO C H -4-NO ; >¼eC(O)NHSO2CF3) (data for extractions showing
*
18b, (c) 18c, (d) 18d, (e) 18e (,¼Mg2þ, B¼Ca2þ, 6¼Sr2þ
,
¼Ba2þ).
7
7
2
6
4
2
precipitate at higher pHs excluded).
100
a)
b)
d)
e)
c)
a)
b)
c)
80
60
40
20
0
100
80
60
40
20
0
0
2
4
6
8 10120 2
4
6
8 10120 2
4
6
8 10120 2 4 6 8 10120 2 4 6 8 1012
pH
0
2
4
6
8
0
2
4
6
8
0
2
4
6
8
Fig. 6. Percent metal loading versus the equilibrium pH of the aqueous phase for
pH
pH
pH
competitive solvent extraction of AEMC into chloroform by 1,2-alternate, di-ionizable
calix[4]arene-1,2-crown-4 ligands 19aee with eO(CH2)4C(O)Y side arms. (a) 19a , (b)
*
Fig. 8. Percent metal loading versus the equilibrium pH of the aqueous phase for
19b
*
, (c) 19c
*
, (d) 19d
*
, (e) 19e
*
(,¼Mg2þ, B¼Ca2þ, 6¼Sr2þ
,
¼Ba2þ) (data for
7
single species solvent extraction of Pb2þ into chloroform by di-ionizable calix[4]arene-
extractions showing precipitate at higher pHs are excluded).
1,2-crown-4 ligands in three conformations: (a) cone, 11aee, (b) partial-cone, 5aee
and (c) 1,2-alternate, 7aee
(,¼eCO2H; B¼eC(O)NHSO2Me; 6¼eC(O)NHSO2Ph;
¼eC(O)NHSO C H -4-NO ; >¼eC(O)NHSO2CF3) (data for extractions showing
*
,
*
For di(carboxylic acid) 19a, the observed Ca2þ selectivity in-
dicates preferred complexation ofa harder AEMC by the carboxylate-
7
2
6
4
2
precipitate at higher pHs excluded).

A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
10247
Fig. 7 displays the Pb2þ extraction results for di-ionizable p-tert-
b)
c)
a)
100
80
60
40
20
0
butylcalix[4]arene-1,2-crown-4 cone conformers 10aee (panel a),
partial-cone conformers 16aee (panel b), and 1,2-alternate con-
formers 18aee (panel c) with eO(CH2)3C(O)Y-containing side arms.
Ligands 10a, 10d, and 10e with cone conformations and 18a with
a 1,2-alternate conformation were found to be very good Pb2þ
extractants. Ligand 10e with a cone conformation reached a maxi-
mum loading of 98% and cone di(carboxylic acid) ligand 18a reached
99%. As a group, the partial-cone ligands 16a-e were the weakest
Pb2þ extractants. This suggests that for optimal coordination with
Pb2þ both acidic side arms should be on the same side of the pol-
yether unit.
Di(carboxylic acid) ligands 10a,16a, and 18a are as good as, if not
better, Pb2þ extractants than analogues with N-(X)sulfonyl car-
boxamide functions in the side arms. This change from the AEMC
extraction behavior shown in Fig. 6 presumably results from the
intermediate hardness/softness of Pb2þ
.
0
2
4
6
8
0
2
4
6
8
0
2
4
6
8
Fig. 8 presents the extraction results for di-ionizable p-tert-
butylcalix[4]arene-1,2-crown-4 cone conformers 11aee (panel a),
partial-cone conformers 17aee (panel b), and 1,2-alternate con-
formers 19aee (panel c) with eO(CH2)4C(O)Y-containing side arms.
Similar to the ligands with one less carbon in the side arm, cone
ligands 11a, 11d, and 11e and 1,2-alternate ligands 19a and 19e
were very good Pb2þ extractants. Di(carboxylic acid) 11a in the cone
conformation showed the highest Pb2þ loading in reaching a max-
imum loading of 99%.
From comparison of the results presented in Figs. 7 and 8, it is
seen that the partial-cone conformers 17aee were the poorest Pb2þ
extractants of the six series of di-ionizable calix[4]arene-1,2-
crown-4 ligands considered in this study. This is consistent with
preferred coordination of Pb2þ by two acidic side arms on the same
side of the polyether unit.
pH
pH
pH
Fig. 9. Percent metal loading versus the equilibrium pH of the aqueous phase for
single species solvent extraction of Hg2þ into chloroform by di-ionizable calix[4]arene-
1,2-crown-4 ligands in three conformations: (a) cone, 10aee, (b) partial-cone, 16aee,
and (c) 1,2-alternate, 18aee (,¼eCO2H; B¼eC(O)NHSO2Me; 6¼eC(O)NHSO2Ph;
¼eC(O)NHSO C H -4-NO ; >¼eC(O)NHSO CF ).
7
2
6
4
2
2
3
b)
a)
c)
100
80
60
40
20
0
For thecone series 11 and1,2-alternate series 19, the di(carboxylic
acid) ligands were as good as, if not better, Pb2þ extractants than
analogues with N-(X)sulfonyl carboxamide functions in the side
arms.
2.3.3. Solvent extraction of Hg2þ by di-ionizable p-tert-butylcalix[4]
arene-1,2-crown-4 ligands. The published results for solvent ex-
traction of soft Hg2þ from aqueous solutions into chloroform by
cone ligands 2bee (m¼1) with short eOCH2C(O)NHSO2X side arms
showed high efficiency.12 In single species solvent extractions, Hg2þ
loadings were very high and exceeded 90% in all cases. However for
the di(carboxylic acid) analogue 2a, the maximum loading was only
about 50%.
0
2
4
6
8
0
2
4
6
8
0
2
4
6
8
pH
pH
pH
Fig. 10. Percent metal loading versus the equilibrium pH of the aqueous phase for
single species solvent extraction of Hg2þ into chloroform by di-ionizable calix[4]arene-
1,2-crown-4 ligands in three conformations: (a) cone, 11aee, (b) partial-cone, 17aee,
and (c) 1,2-alternate, 19aee (,¼eCO2H; B¼eC(O)NHSO2Me; 6¼eC(O)NHSO2Ph;
¼eC(O)NHSO C H e4-NO ; >¼eC(O)NHSO CF ).
From single species solvent extractions of aqueous Hg2þ solu-
tions (0.25 mM) by 0.25 mM solutions of di-ionizable ligands
10aee, 11aee, 16aee, 17aee, 18aee, and 19aee, plots of Hg2þ
loading of the organic phase versus the equilibrium pH of the
aqueous phase are presented in Figs. 9 and 10.
7
2
6
4
2
2
3
Fig. 9 displays the Hg2þ extraction results for di-ionizable calix[4]
arene-1,2-crown-4 cone conformers 10aee, partial-cone conformers
16aee, and 1,2-alternate conformers 18aee with eO(CH2)3C(O)Y-
containing side arms. Cone ligands 10aee and 1,2-alternate ligands
18bee are very good extractants for Hg2þ. Cone ligand 10d reached
a maximum loading of 97% and 1,2-alternate ligand 18d reached 94%.
The highest Hg2þ loading for the partial-cone series was 75%,
exhibited by ligand 16e. Overall, the extraction efficiency for Hg2þ
decreases in the order: 10 (cone)>18 (1.2-alternate)>16 (partial-
cone). These results suggest that the cone conformation gives the
Fig. 10 presents the extraction results for di-ionizable p-tert-
butylcalix[4]arene-1,2-crown-4 cone conformers 11aee (panel a),
partial-cone conformers 17aee (panel b), and 1,2-alternate con-
formers 19aee with eO(CH2)4C(O)Y-containing side arms.
Comparison of the extraction profiles shown in Figs. 9 and 10
reveals rather close similarity in the effects of conformation and
identity of the acidic group in the side arm. It appears that extending
the acidic side arm length by one methylene group results in only
minor changes in the efficiency with which Hg2þ can be extracted.
best
p
-cation interactions for extraction of soft Hg2þ
.
3. Conclusions
For extractions of Hg2þ, the di(carboxylic acid) ligands partial-
cone 16a and 1,2-alternate 18a perform significantly poorer than
ligands 16bee and 18bee with N-(X)sulfonyl carboxamide func-
tions in the side arms. The hard carboxylate group does not co-
Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands
10aee, 11aee, 16aee, 17aee, 18aee, and 19aee with cone, partial-
cone, or unusual 1,2-alternate conformations, elongated side arms,
and different groups in the acidic side arms have been synthesized.
ordinate as well with soft Hg2þ
.

10248
A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
The acidic side arms eO(CH2)nC(O)Y with n¼3 and 4 and Y¼eOH,
eNHSO2Me, eNHSO2Ph, eNHSO2C6H4e4-NO2, and eCF3. Struc-
tures of the new compounds were verified by 1H and 13C NMR
spectroscopy, IR spectroscopy, and combustion analysis.
The influence of these systematic structural variations upon the
efficiency and selectivity of divalent metal ion complexation was
evaluated by solvent extraction from aqueous solutions into chlo-
roform. Hard AEMC, intermediate Pb2þ, and soft Hg2þ were utilized
to vary the properties of the divalent metal ions being extracted.
Results are compared with those published for cone di-ionizable p-
tert-butylcalix[4]arene-1,2-crown-4 ligands 2aee with short acidic
side arms of eOCH2C(O)Y.11,12
Ligands 10aee, 11aee, 16aee, 17aee, and 18aee showed poor
efficiency in competitive AEMC extractions from aqueous solutions
into chloroform. Surprisingly, ligands 19bee with the 1,2-alternate
conformation and the longer side arms (n¼4) containing N-(X)
sulfonyl carboxamide groups performed moderately well as AEMC
extractants. They exhibited good Ba2þ selectivity and moderate-to-
high metal loadings. However, their behavior is still surpassed by
the high selectivity and efficiency for Ba2þ extraction reported
previously for ligands 2aee with m¼1. Molecular modeling shows
a favorable geometry for Ba2þ complexed by cone, di-ionized calix
[4]arene-1,2-crown-4 having short side arms.
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. Triethylene glycol ditosy-
late22 was prepared according to a literature procedure.
4.2. Synthesis of p-tert-butylcalix[4]arene-1,2-crown-4
compounds
4.2.1. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,26-dihydroxycalix[4]
arene-1,2-crown-4 (7). To a suspension of p-tert-butylcalix[4]arene
(6) (5.00 g, 7.71 mmol) in MeCN (500 mL) was added Cs2CO3
(25.12 g, 77.10 mmol). The mixture was stirred at room temperature
for a 1-h period. A solution of triethylene glycol ditosylate (3.90 g,
8.51 mmol) in MeCN (50 mL) was added to the mixture dropwise
over a 1-h period and the mixture was stirred at reflux for 48 h. The
solvent was evaporated in vacuo and CH2Cl2 was added to the res-
idue. The organic layer was washed with 5% aqueous HCl (100 mL)
and water (3ꢁ100 mL), then dried over MgSO4. The solvent was
evaporated in vacuo and the product was chromatographed on
silica gel with hexanes/EtOAc (2:1) as eluent to give white solid 7
(2.29 g, 39% yield) with mp 108e110 ꢂC (lit.21 mp 110e112 ꢂC).
For single species solvent extractions of intermediate Pb2þ, cone
ligands 10aee and 11aee and 1,2-alternate ligands 18aee and
19aee were found to be efficient extractants with maximum
loadings of 89e99%. This compares well with ligands 2aee (m¼1)
for which metal loadings of >90% were reported.12 Partial-cone li-
gands 16aee and particularly 17aee are found to be poor extrac-
4.2.2. General procedure for preparation of cone 5,11,17,23-
tetrakis(1,1-dimethylethyl)-25,26-bis[3-(ethoxycarbonyl)(n)-oxy]ca-
lix[4]arene-1,2-crown-4 compounds 8 and 9. To a solution of 7
(1.00 g, 1.31 mmol) in THF (20 mL) was added NaH (0.13 g,
5.24 mmol) and the mixture was stirred under nitrogen for a 1-h
period. A solution of the appropriate alkylating agent (3.93 mmol)
inTHF (10 mL total volume) was added dropwise via a syringe pump
over a 1-h period. The mixture was stirred at reflux for 1 d and then
a second portion of the alkylating agent (3.93 mmol) was added
dropwise. After refluxing for a total of 2 d, the solvent was evapo-
rated in vacuo and CH2Cl2 (30 mL) was added to the residue. The
organic layer was washed with 5% aqueous HCl (30 mL) and water
(3ꢁ30 mL), dried over MgSO4, and evaporated in vacuo. The residue
was chromatographed on silica gel with hexanes/EtOAc (10:1) as
eluent.
tants for Pb2þ
.
For single species solvent extractions of soft Hg2þ, cone ligands
10aee and 11aee and 1,2-alternate N-(X)sulfonyl carboxamide li-
gands 18bee and 19bee were found to be effective. Most of these
ligands reached maximum Hg2þ loadings of >90%. This compares
well to ligands 2bee (m¼1), which are reported12 to reach >90%
loading of Hg2þ
.
Thus, it is found that that the most effective length for the acidic
side arms in the di-ionizable calix[4]arene-1,2-crown-4 ligands
depends upon the divalent metal ion being extracted. For hard
Ba2þ, short acidic side arms are clearly the best. For intermediate
Pb2þ and soft Hg2þ, ligands with elongated acidic side arms con-
taining soft N-(X)sulfonyl carboxamide functions and cone or 1,2-
alternate conformations are as effective as the reported cone li-
gands 2 (m¼1) with short acidic side arms.
4.2.2.1. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis[3-
(ethoxycarbonyl)propoxy]calix[4]arene-1,2-crown-4 (8). An off-
white solid with mp 57e59 ꢂC was isolated in 57% yield. IR (de-
posit from CH2Cl2 solution on a NaCl plate): 1740 (C]O) cmꢀ1. 1H
NMR (CDCl3):
d 1.07 (s, 18H, C(CH3)3), 1.08 (s, 18H, C(CH3)3), 1.27 (t,
4. Experimental
4.1. General
J¼7.0 Hz, 6H, CH3), 2.35 (quintet, J¼7.0 Hz, 4H, CH2CH2C]O),
2.43e2.60 (m, 4H, CH2C]O), 3.10, 4.81 (AX, J¼12.5 Hz, 4H,
ArCH2Ar), 3.14, 4.35 (AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.15, 4.33 (AX,
J¼12.5 Hz, 2H, ArCH2Ar), 3.70e3.80 (m, 2H, OCH2CH2O), 3.80e3.99
(m, 10H, OCH2, OCH2CH2O), 4.16 (q, J¼7.0 Hz, 4H, OCH2CH3),
4.19e4.24 (m, 2H, OCH2CH2O), 4.25e4.32 (m, 2H, OCH2CH2O),
Melting points were determined with a Mel-Temp melting point
apparatus. Infrared (IR) spectra were recorded with a Nicolet 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 at 500 MHz and 13C at 126 MHz) spectrom-
eter at 296 K in CDCl3 with TMS as internal standard. Chemical shifts
6.68e6.89 (m, 8H, ArH). 13C NMR (CDCl3):
d 14.3, 25.6, 30.1, 30.8,
31.2, 31.2, 31.4, 31.4, 33.8, 33.8, 60.3, 70.2, 70.5, 7.3.2, 74.2, 124.9,
125.1, 125.1, 133.5, 133.7, 134.4, 144.5, 144.6, 153.1, 153.2, 173.3. Anal.
Calcd for C62H86O10: C, 75.12; H, 8.74. Found: C, 74.72; H, 8.66.
(
d
) are given in parts per million (ppm) downfield from TMS and
4.2.2.2. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis[4-
(ethoxycarbonyl)butoxy]calix[4]arene-1,2-crown-4 (9). A tan oil was
isolated in 52% yield. IR (deposit from CH2Cl2 solution on a NaCl
coupling constant values (J) are given in hertz. Combustion analysis
was performed by Desert Analytics Laboratory (now Columbia
Analytical Services) of Tucson, Arizona. For compounds 10aee, 13,
16a, 17c, and 17d, the combustion analysis results indicated the
presence of small amounts of CH2Cl2. This was verified by singlets at
plate): 1739 (C]O) cmꢀ1. 1H NMR (CDCl3):
d 1.07 (s, 18H, C(CH3)3),
1.08 (s, 18H, C(CH3)3), 1.26 (t, J¼7.0 Hz, 6H, CH3), 1.76 (quintet,
J¼7.5 Hz, 4H, OCH2CH2), 2.04 (quintet, J¼7.5 Hz, 4H, CH2CH2C]O),
2.42 (td, J¼7.5, 3.0 Hz, 4H, CH2C]O), 3.10, 4.75 (AX, J¼12.5 Hz, 1H,
ArCH2Ar), 3.12, 4.36 (AX, J¼12.5 Hz, 1H, ArCH2Ar), 3.14, 4.31 (AX,
J¼12.5 Hz, 2H, ArCH2Ar), 3.68e3.81 (m, 3H, OCH2), 3.81e3.96 (m,
10H, OCH2CH2O), 4.06e4.18 (m, 10H, OCH2CH2O), 4.14 (q, J¼7.5 Hz,
d
5.32 in their 1H NMR spectra. For compounds 11a,12,17a, and 19a,
the combustion analysis results indicated the presence of small
amounts of EtOAc. This was verified by singlets at 2.05, quartets at
4.12, and triplets at
1.26 in their 1H NMR spectra.
d
d
d

A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
10249
4H, OCH2CH3), 4.25e4.35 (m, 1H, OCH2), 6.69e6.89 (m, 8H, ArH).
13C NMR (CDCl3):
14.3, 21.6, 29.7, 30.2, 30.8, 31.1, 31.4, 33.8, 33.8,
34.2, 60.2, 70.3, 70.6, 73.0, 74.7, 76.7, 124.9, 125.0, 125.0, 133.6, 133.7,
134.2, 144.4, 144.6, 153.1, 153.3, 173.6. Anal. Calcd for C64H90O10: C,
75.41; H, 8.90. Found: C, 75.26; H, 9.12.
5.30 mmol) in THF (10 mL). This mixture was stirred for a 2-h period
before the dropwise addition of the di(acid chloride) dissolved in
THF (5 mL). The mixture was stirred overnight (3 h for p-nitro-
benzenesulfonamide) at room temperature after which the solvent
was evaporated in vacuo. The residue was dissolved in CH2Cl2
(30 mL) and H2O (10 mL) was carefully added. The organic layer was
washed with 6 N HCl (30 mL), dried over MgSO4, and evaporated in
vacuo. Yields, melting points, spectra, and combustion analysis data
for compounds 10bee are given in Supplementary data.
d
4.2.3. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis[3-(car-
boxy)propoxy]calix[4]arene-1,2-crown-4 (10a). A solution of diester
8 (7.41 g, 7.48 mmol), 10% aqueous NMe4OH (250 mL), and THF
(250 mL) was refluxed for 1 d, cooled to room temperature, and
stirred with 6 N aqueous HCl (150 mL) for a 1-h period. After
evaporation of the THF in vacuo, the white precipitate was filtered
and dissolved in CH2Cl2 (200 mL). The aqueous filtrate was
extracted with CH2Cl2 (2ꢁ200 mL). The combined organic layers
were washed with 6 N aqueous HCl until pH¼1 and dried over
MgSO4. The solvent was evaporated in vacuo to give an off-white
solid 10a (6.67 g, 95%) with mp 157e159 ꢂC. IR (deposit from
CH2Cl2 solution on a NaCl plate): 3684e2406 (OH), 1712 (C]O)
4.2.6. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,26-bis[3-(N-(X)sulfo-
nyl
carbamoylbutoxy)]calix[4]arene-1,2-crown-4
compounds
11bee. Di(carboxylic acid) 11a (0.50 g, 0.52 mmol) was dried with
a benzene azeotrope before addition of oxalyl chloride (0.45 mL,
5.20 mmol) in benzene (50 mL). The solution was stirred at room
temperature for a 6-h period. Formation of the di(acid chloride)
was confirmed by an IR shift of the C]O absorption from 1712 in
11a to 1796 cmꢀ1. The benzene was evaporated in vacuo at ambient
temperature to avoid formation of the acid anhydride. The di(acid
chloride) residue was dried under oil-pump vacuum for a 30-min
period. The sodium sulfonamidate salt was prepared under nitro-
gen by dropwise addition of the appropriate sulfonamide
(1.17 mmol) dissolved in THF (10 mL) to a mixture of NaH (0.13 g,
5.20 mmol) in THF (10 mL). The mixture was stirred for a 2-h period
before the dropwise addition of the di(acid chloride) dissolved in
THF (5 mL). The mixture was stirred overnight at room temperature
after which the solvent was evaporated in vacuo. The residue was
dissolved in CH2Cl2 (30 mL) and H2O (10 mL) was carefully added.
The organic layer was washed with 6 N HCl (30 mL), dried over
MgSO4, and evaporated in vacuo. Yields, melting points, spectra,
and combustion analysis data for compounds 11bee are given in
Supplementary data.
cmꢀ1 1H NMR (CDCl3):
. d 1.07 (s, 18H, C(CH3)3), 1.08 (s, 18H,
C(CH3)3), 2.31e2.53 (m, 4H, CH2CH2C]O), 2.53e2.77 (m, 4H,
CH2C]O), 3.10, 4.86 (AX, J¼12.5 Hz, 4H, ArCH2Ar), 3.15, 4.36 (AX,
J¼12.5 Hz, 2H, ArCH2Ar), 3.17, 4.30 (AX, J¼12.5 Hz, 2H, ArCH2Ar),
3.71e3.80 (m, 2H, OCH2CH2O), 3.80e3.92 (m, 8H, OCH2, OCH2
-
CH2O), 3.92e4.00 (m, 2H, OCH2CH2O), 4.18e4.30 (m, 4H, OCH2
-
CH2O), 6.75e6.87 (m, 8H, ArH). 13C NMR (CDCl3):
d
25.3, 29.9, 30.6,
31.1, 31.2, 31.4, 31.4, 33.8, 70.1, 70.6, 73.2, 74.3, 124.9, 125.1, 125.1,
133.4, 133.6, 133.7, 134.7, 144.5, 144.7, 153.0, 153.1, 179.8. Anal. Calcd
for C58H78O10$CH2Cl2: C, 69.46; H, 7.90. Found: C, 69.38; H, 7.97.
4.2.4. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis[3-(car-
boxy)butoxy]calix[4]arene-1,2-crown-4 (11a). A solution of diester 9
(4.51 g, 4.42 mmol), 10% aqueous NMe4OH (200 mL), and THF
(200 mL) was refluxed for 1 d. The solution was cooled to room
temperature and stirred with 6 N aqueous HCl (80 mL) for a 1-h
period. After evaporation of the THF in vacuo, a white precipitate
was filtered and dissolved in CH2Cl2 (150 mL). The aqueous filtrate
was extracted with CH2Cl2 (2ꢁ150 mL). The combined organic
layers were washed with 6 N aqueous HCl until pH¼1 and dried
over MgSO4. The solvent was evaporated in vacuo to give white
solid 11a (3.94 g, 93%) with mp 181e182 ꢂC. IR (deposit from CH2Cl2
4.2.7. Preparation of 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis
[3-(ethoxycarbonyl)propoxy]calix[4]arene-1,2-crown-4 compounds
8, 12, and 14 and 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis[4-
(ethoxycarbonyl)butoxy]calix[4]arene-1,2-crown-4 compounds 11,
13, and 15 in cone, partial-cone, and 1,2-alternate conformations. To
a solution of calixcrown 7 (3.60 g, 4.72 mmol) in MeCN (270 mL)
was added Cs2CO3 (7.70 g, 23.66 mmol). The mixture was stirred
under nitrogen for a 1-h period and the appropriate alkylating
agent (37.30 mmol) was added in one portion. The mixture was
refluxed for 1 d and then quenched with 5% aqueous HCl (70 mL).
After evaporation of the solvent in vacuo, the residue was dissolved
in CH2Cl2 and the organic layer was washed with water (3ꢁ), dried
over MgSO4, and evaporated in vacuo. The crude product mixture
was purified by chromatography on silica gel with hexanes/EtOAc
(10:1) as eluent to afford three fractions.
solution on a NaCl plate): 3521e1974 (OH), 1707 (C]O) cmꢀ1
.
1H
NMR (CDCl3): 1.20e1.28 (m, 4H, OCH2CH2), 1.30 (s, 18H, C(CH3)3),
d
1.34 (s, 18H, C(CH3)3), 1.36e1.46 (m, 4H, CH2CH2C]O), 2.18 (td,
J¼8.0, 3.0 Hz, 4H, CH2C]O), 2.75 (quintet, J¼5.0 Hz, 2H, OCH2
-
CH2O), 3.13, 4.34 (AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.14, 4.12 (AX,
J¼12.5 Hz, 2H, ArCH2Ar), 3.27e3.51 (m, 10H, OCH2, OCH2CH2O),
3.56e3.72 (m, 4H, OCH2CH2O), 3.84 (s, 4H, ArCH2Ar), 6.97e7.03 (m,
4H, ArH), 7.16e7.21 (m, 2H, ArH), 7.23e7.26 (m, 2H, ArH). 13C NMR
(CDCl3):
d 20.9, 28.4, 28.7, 29.7, 31.7, 31.8, 33.6, 34.0,34.0, 39.0, 67.9,
69.4, 69.8, 72.0, 125.3, 125.4, 125.5, 125.6, 132.0, 132.1, 133.9, 134.1,
4.2.7.1. With ethyl bromobutyrate as the alkylating agent.
Fraction A. Cone diester 8 was isolated in 41% yield.
144.2,144.3,153.3,153.8,180.0. Anal. Calcd for C60H82O10$0.5EtOAc:
C, 73.92; H, 8.60. Found: C, 73.97; H, 8.61.
Fraction B. 1,2-Alternate 5,11,17,23-tetrakis(1,1-dimethylethyl)-
25,26-bis[3-(ethoxycarbonyl)propoxy]calix[4]arene-1,2-crown-4 (14).
The white solid with mp 84e85 ꢂC was isolated in 15% yield. IR
(deposit from CH2Cl2 solution on a NaCl plate): 1736 (C]O) cmꢀ1.1H
4.2.5. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis[3-(N-(X)
sulfonyl carbamoyl-propoxy)]calix[4]arene-1,2-crown-4 compounds
10bee. Di(carboxylic acid) 10a (0.50 g, 0.53 mmol) was dried with
a benzene azeotrope before addition of oxalyl chloride (0.46 mL,
5.30 mmol) in benzene (50 mL). The solution was stirred at room
temperature for a 6-h period. Formation of the di(acid chloride) was
confirmed by an IR shift of the C]O absorption from 1712 to
1792 cmꢀ1. The benzene was evaporated in vacuo at ambient tem-
perature to avoid formation of the acid anhydride. The di(acid
chloride) residue was subjected to oil-pump vacuum for a 30-min
period. The sodium sulfonamidate salt was prepared under nitro-
gen by dropwise addition of a solution of the appropriate sulfon-
amide (1.17 mmol) in THF (10 mL) to a mixture of NaH (0.13 g,
NMR (CDCl3):
d
1.21 (t, J¼7.0 Hz, 6H, CH3), 1.24e1.28 (m, 4H,
CH2CH2C]O),1.30 (s,18H, C(CH3)3),1.34 (s,18H, C(CH3)3),1.99e2.16
(m, 4H, CH2C]O), 2.76 (td, J¼10.0, 5.0 Hz, 2H, OCH2CH2O), 3.13, 4.35
(AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.16, 4.13 (AX, J¼12.5 Hz, 2H,
ArCH2Ar), 3.28e3.38 (m, 3H, OCH2CH2O), 3.38e3.52 (m, 7H, OCH2,
OCH2CH2O), 3.56e3.70 (m, 4H, OCH2CH2O), 3.82, 3.88 (AB,
J¼16.5 Hz, 4H, ArCH2Ar), 4.06 (q, J¼7.0 Hz, 4H, OCH2CH3), 6.96e7.03
(m, 2H, ArH), 7.03e7.09 (m, 2H, ArH), 7.15e7.22 (m, 2H, ArH),
7.22e7.26 (m, 2H, ArH).13C NMR (CDCl3):
d 14.2, 28.8,19.0,19.7, 30.8,
31.5, 31.6, 31.6, 31.8, 34.0, 34.0, 38.9, 60.1, 67.9, 69.4, 70.0, 71.6,125.4,
125.5,125.6,132.1,132.2,133.9,134.2,144.3,144.4,153.4,153.8,173.1.

10250
A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
Anal. Calcd for C62H86
73.88; H, 8.69.
O
10$0.8EtOAc: C, 73.75; H, 8.77. Found: C,
2H, OCH2CH2), 2.24e2.28 (m, 2H, CH2C]O), 2.41e2.54 (m, 1H,
CH2C]O), 2.54e2.66 (m, 1H, CH2C]O), 3.09, 4.28 (AX, J¼12.5 Hz,
2H, ArCH2Ar), 3.10, 4.02 (AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.13e4.19 (m,
20H, OCH2, OCH2CH2O, ArCH2Ar), 6.63e6.78 (m, 2H, ArH),
6.86e6.96 (m, 2H, ArH), 7.04e7.30 (m, 4H, ArH). 13C NMR (CDCl3):
Fraction C. Partial-cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-
25,26-bis[3-(ethoxycarbonyl)propoxy]calix[4]arene-1,2-crown-4
(12). A white solid with mp 63e64 ꢂC was isolated in 22% yield. IR
(deposit from CH2Cl2 solution on a NaCl plate): 1732 (C]O) cmꢀ1
.
d 25.2, 26.1, 29.7, 30.2, 30.5, 31.2, 31.3, 31.4, 31.6, 31.9, 32.0, 33.7,
1H NMR (CDCl3):
d
1.05 (s, 9H, C(CH3)3), 1.07 (s, 9H, C(CH3)3),
33.8, 34.1, 34.1, 38.1, 38.2, 67.4, 69.6, 69.8, 69.8, 70.7, 72.1, 72.4, 73.2,
125.2, 125.4, 125.6, 125.8, 126.1, 126.2, 127.1, 127.9, 131.8, 132.1, 132.6,
132.9, 133.3, 133.5, 135.2, 135.3, 143.6, 144.1, 144.2, 145.6, 152.4,
1.22e1.28 (m, 6H, CH3), 1.32 (s, 9H, C(CH3)3), 1.46 (s, 9H, C(CH3)3),
1.89 (quintet, J¼8.0 Hz, 2H, OCH2CH2), 2.10e2.26 (m, 4H, CH2C]O,
OCH2CH2), 2.35e2.56 (m, 2H, CH2C]O), 3.06, 4.36 (AX, J¼12.5 Hz,
2H, ArCH2Ar), 3.08, 4.05 (AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.13e4.19
(m, 24H, OCH2, OCH2CH2O, OCH2CH3, ArCH2Ar), 6.64e6.74 (m, 2H,
ArH), 6.84e6.92 (m, 2H, ArH), 6.98e7.25 (m, 4H, ArH). 13C NMR
153.0, 153.3, 155.1, 177.1, 178.7. Anal. Calcd for C58H78O10$0.4CH2Cl2:
C, 72.37; H, 8.19. Found: C, 72.25; H, 8.20.
4.2.9. Partial-cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis
[3-(carboxy)butoxy]calix[4]arene-1,2-crown-4 (17a). The procedure
was the same as that employed for preparation of 11a, but starting
from 13. An off-white solid with mp 184e186 ꢂC was obtained in
94% yield. IR (deposit from CH2Cl2 solution on a NaCl plate):
(CDCl3): d 14.3, 25.6, 25.8, 30.2, 30.7, 31.0, 31.4, 31.5, 31.7, 33.7, 33.8,
34.1, 34.1, 38.0, 38.1, 60.3, 60.3, 66.8, 69.4, 69.9, 70.6, 70.9, 72.3, 72.6,
73.3, 98.6, 125.2, 125.4, 125.7, 125.8, 125.8, 126.1, 127.2, 128.1, 131.9,
123.2, 123.6, 123.0, 133.1, 133.3, 135.2, 135.5, 143.4, 143.9, 144.1,
145.3, 152.7, 153.3, 153.6, 155.1, 172.9, 173.1. Anal. Calcd for
C62H86O10: C, 75.12; H, 8.74. Found: C, 74.73; H, 8.18.
3548e2015 (OH), 1714 (C]O) cmꢀ1. 1H NMR (CDCl3):
d 1.02 (s, 9H,
C(CH3)3), 1.04 (s, 9H, C(CH3)3), 1.34 (s, 9H, C(CH3)3), 1.45 (s, 9H,
C(CH3)3), 1.63 (quintet, J¼7.5 Hz, 2H, CH2CH2C]O), 1.71e1.82 (m,
3H, OCH2CH2), 1.82e1.96 (m, 1H, OCH2CH2), 2.37 (t, J¼7.5 Hz, 2H,
CH2C]O), 2.42 (t, J¼7.5 Hz, 2H, CH2C]O), 3.06, 4.26 (AX,
J¼12.5 Hz, 2H, ArCH2Ar), 3.07, 4.02 (AX, J¼12.5 Hz, 2H, ArCH2Ar),
3.48e4.05 (m, 16H, OCH2, OCH2CH2O), 3.65 (AB, J¼7.5 Hz, 2H,
ArCH2Ar), 6.58e6.68 (m, 2H, ArH), 6.78e6.88 (m, 2H, ArH),
4.2.7.2. With ethyl bromovalerate as the alkylating agent.
Fraction A. Cone diester 9 was obtained in 36% yield.
Fraction B. 1,2-Alternate 5,11,17,23-tetrakis(1,1-dimethylethyl)-
25,26-bis[3-(ethoxycarbonyl)butoxy]calix[4]arene-1,2-crown-4 (15).
A white solid with mp 48e50 ꢂC was obtained in 16% yield. IR
(deposit from CH2Cl2 solution on a NaCl plate): 1732 (C]O) cmꢀ1
.
7.20e7.26 (m, 4H, ArH). 13C NMR (CDCl3):
d 21.1, 22.0, 29.7, 30.1, 30.1,
1H NMR (CDCl3):
d
1.22 (t, J¼7.5 Hz, 6H, CH3), 1.24e1.28 (m, 4H,
30.2, 30.5, 31.3, 31.4, 31.7, 31.9, 33.6, 33.7, 33.8, 34.1, 34.1, 34.5, 38.0,
38.1, 66.1, 67.7, 69.3, 69.7, 71.4, 72.3, 72.7, 73.8, 125.2, 125.4, 125.7,
125.8, 126.1, 127.1, 128.1, 131.6, 132.0, 132.4, 132.6, 133.1, 133.3, 135.5,
135.5, 143.2, 143.6, 143.9, 145.5, 152.3, 153.2, 153.5, 155.3, 177.3,
OCH2CH2), 1.30 (s, 18H, C(CH3)3), 1.34 (s, 18H, C(CH3)3), 1.36e1.49
(m, 4H, CH2CH2C]O), 2.13 (t, J¼8.0 Hz, 4H, CH2C]O), 2.75 (quintet,
J¼5.5 Hz, 2H, OCH2CH2O), 3.12, 4.35 (AX, J¼12.5 Hz, 2H, ArCH2Ar),
3.14, 4.14 (AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.28e3.48 (m, 10H, OCH2,
OCH2CH2O), 3.54e3.68 (m, 4H, OCH2, OCH2CH2O), 3.86, 3.82 (AB,
J¼16.5 Hz, 4H, ArCH2Ar), 4.08 (q, J¼7.5 Hz, 4H, OCH2CH3),
6.94e7.05 (m, 4H, ArH), 7.12e7.22 (m, 2H, ArH), 7.22e7.29 (m, 2H,
178.8. Anal. Calcd for C60H82O10$1.4EtOAc: C, 72.51; H, 8.64. Found:
C, 72.52; H, 8.45.
4.2.10. 1,2-Alternate 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis
[3-(carboxy)propoxy]calix[4]arene-1,2-crown-4 (18a). The pro-
cedure was the same as that employed for preparation of 10a, but
starting from 14. White solid with mp 172e175 ꢂC was obtained in
84% yield. IR (deposit from CH2Cl2 solution on a NaCl plate):
ArH). 13C NMR (CDCl3):
33.9, 34.0, 34.0, 39.0, 60.1, 67.9, 69.4, 69.9, 71.9, 125.3, 125.5, 125.6,
132.0, 132.1, 133.9, 134.1, 144.2, 144.3, 153.4, 153.9, 173.4. Anal. Calcd
d 14.2, 21.1, 28.6, 28.8, 29.0, 29.7, 31.7, 31.8,
for C64H90O10$0.2CH2Cl2: C, 74.40; H, 8.79. Found: C, 74.29; H, 9.02.
Fraction C. Partial-cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-
25,26-bis[3-(ethoxycarbonyl)butoxy]calix[4]arene-1,2-crown-4 (13).
A white solid with mp 77e78 ꢂC was isolated in 20% yield. IR (de-
posit from CH2Cl2 solution on a NaCl plate): 1740 (C]O) cmꢀ1. 1H
3548e2427 (OH), 1711 (C]O) cmꢀ1 1H NMR (CDCl3):
. d 1.20e1.28
(m, 2H, CH2CH2C]O), 1.30 (s, 18H, C(CH3)3), 1.34 (s, 18H, C(CH3)3),
1.48e1.60 (m, 2H, CH2CH2C]O), 1.95e2.10 (m, 2H, CH2C]O),
2.10e2.24 (m, 2H, CH2C]O), 2.79 (td, J¼10.0, 5.0 Hz, 2H, OCH2
-
NMR (CDCl3):
d
1.02 (s, 9H, C(CH3)3), 1.04 (s, 9H, C(CH3)3), 1.22e1.29
CH2O), 3.14, 4.37 (AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.15, 4.13 (AX,
J¼12.5 Hz, 2H, ArCH2Ar), 3.30e3.38 (m, 2H, OCH2CH2O), 3.38e3.45
(m, 6H, OCH2, OCH2CH2O), 3.45e3.53 (m, 2H, OCH2CH2O),
3.57e3.72 (m, 4H, OCH2CH2O), 3.85 (s, 4H, ArCH2Ar), 6.98e7.05 (m,
(m, 6H, CH3), 1.34 (s, 9H, C(CH3)3), 1.45 (s, 9H, C(CH3)3), 1.55e1.814
(m, 6H, OCH2CH2, CH2CH2C]O), 1.89 (quintet, J¼7.5 Hz, 2H,
OCH2CH2), 2.32 (t, J¼7.5 Hz, 2H, CH2C]O), 2.37 (t, J¼7.5 Hz, 2H,
CH2C]O), 3.05, 4.32 (AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.06, 4.03
4H, ArH), 7.17e7.26 (m, 4H, ArH). 13C NMR (CDCl3):
d 24.2, 28.7, 28.9,
(AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.38e4.06 (m, 16H, OCH2, OCH2
30.6, 31.6, 31.7, 34.0, 34.0, 39.0, 68.0, 39.4, 39.9, 71.4, 125.3, 125.4,
125.6, 125.6, 132.0, 120.0, 133.9, 134.1, 144.3, 144.5, 153.4, 153.5,
179.9. Anal. Calcd for C58H78O10: C, 74.49; H, 8.41. Found: C, 74.56;
H, 8.39.
-
CH2O), 3.65 (s, 4H, ArCH2Ar), 4.14 (q, J¼7.5 Hz, 4H, OCH2CH3),
6.58e6.68 (m, 2H, ArH), 6.78e6.86 (m, 2H, ArH), 7.07e7.24 (m, 4H,
ArH). 13C NMR (CDCl3):
d 14.2, 21.4, 21.6, 29.9, 30.2, 30.3, 30.7, 31.4,
31.4, 31.7, 31.9, 33.7, 33.7, 34.1, 34.1, 34.1, 34.2, 38.0, 38.2, 60.2, 60.3,
66.5, 68.1, 69.4, 70.3, 71.6, 72.4, 72.9, 73.9, 124.1, 125.2, 125.4, 125.7,
125.8, 126.0, 127.1, 128.2, 131.7, 132.1, 132.4, 132.7, 133.0, 133.2,135.4,
135.6, 143.1, 143.5, 143.8, 145.3, 152.5, 153.4, 153.7, 155.3, 173.3,
173.5. Anal. Calcd for C64H90O10: C, 75.41; H, 8.90. Found: C, 75.59;
H, 8.54.
4.2.11. 1,2-Alternate 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis
[3-(carboxy)butoxy]calix[4]arene-1,2-crown-4
(19a). The
pro-
cedure was the same as that employed for preparation of 11a, but
starting from 15. An off-white solid with mp 181e182 ꢂC was ob-
tained in 94% yield. IR (deposit from CH2Cl2 solution on a NaCl
plate): 3521e2330 (OH), 1707 (C]O) cmꢀ1 1H NMR (CDCl3):
.
4.2.8. Partial-cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-bis
[3-(carboxy)propoxy]calix[4]arene-1,2-crown-4 (16a). The pro-
cedure was the same as that employed for preparation of 10a, but
starting from 12. An off-white solid with mp 113e116 ꢂC was ob-
tained in 88% yield. IR (deposit from CH2Cl2 solution on a NaCl
d 1.20e1.28 (m, 4H, OCH2CH2), 1.30 (s, 18H, C(CH3)3), 1.34 (s, 18H,
C(CH3)3), 1.36e1.46 (m, 4H, CH2CH2C]O), 2.18 (td, J¼8.0, 3.0 Hz,
4H, CH2C]O), 2.75 (quintet, J¼5.0 Hz, 2H, OCH2CH2O), 3.13, 4.34
(AX, J¼12.5 Hz, 2H, ArCH2Ar), 3.14, 4.12 (AX, J¼12.5 Hz, 2H,
ArCH2Ar), 3.27e3.51 (m, 10H, OCH2, OCH2CH2O), 3.56e3.72 (m, 4H,
OCH2CH2O), 3.84 (s, 4H, ArCH2Ar), 6.97e7.03 (m, 4H, ArH),
plate): 3601e2378 (OH), 1705 (C]O) cmꢀ1. 1H NMR (CDCl3):
d 1.05
(s, 9H, C(CH3)3), 1.07 (s, 9H, C(CH3)3), 1.31 (s, 9H, C(CH3)3), 1.44 (s,
7.16e7.21 (m, 2H, ArH), 7.23e7.26 (m, 2H, ArH). 13C (CDCl3):
d
20.9,
9H, C(CH3)3), 1.84 (quintet, J¼7.5 Hz, 2H, OCH2CH2), 2.12e2.24 (m,
28.4, 28.7, 29.7, 31.7, 31.8, 33.6, 34.0, 34.0, 39.0, 67.9, 69.4, 69.8, 72.0,

A.L. Boston et al. / Tetrahedron 68 (2012) 10241e10251
10251
125.3, 125.4, 125.5, 125.6, 132.0, 132.1, 133.9, 134.1, 144.2, 144.3,
Supplementary data
153.3, 153.8, 180.0. Anal. Calcd for C60H82
8.60. Found: C, 73.97; H, 8.61.
O10$0.5EtOAc: C, 73.92; H,
1He1H HETCOR and 1He13C COSY NMR spectra for new
di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands 10a, 17c,
and 18c (pages S3eS7).
4.2.12. Preparation of 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-
bis[3-(N-(X)sulfonyl carbamoylpropoxy)]calix[4]arene-1,2-crown-4
compounds 16bee and 18bee in partial-cone and 1,2-alternate
conformations. The procedure was the same as that employed for
synthesizing compounds 10bee, but starting from the appropriate
di(carboxylic acid) 16a or 18a. Yields, melting points, spectra, and
combustion analysis data for compounds 16bee and 18bee are
given in Supplementary data.
Table S1. Selected 1H NMR and 13C NMR chemical shifts for
1,2-alternate compounds 18aee and 19aee (page S8).
Yields and characterization data for di-ionizable p-tert-butyl-
calix[4]arene compounds 10bee, 11bee, 16bee, 17bee, 18bee, and
19bee with two elongated, N-(X)sulfonyl carboxamide-containing
side arms (pages S9eS21).
Fig. S7. Profile for competitive solvent extraction of AEMC into
chloroform by cone, di-ionizable calix[4]arene-1,2-crown-4 ligands
10aee with eO(CH2)3C(O)Y side arms (page S22).
4.2.13. Preparation of 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,26-
bis[3-(N-(X)sulfonyl
carbamoylbutoxy)]calix[4]arene-1,2-crown-4
Fig. S8. Profile for competitive solvent extraction of AEMC into
chloroform by cone, di-ionizable calix[4]arene-1,2-crown-4 ligands
11aee with eO(CH2)4C(O)Y side arms (page S22).
compounds 17bee and 19bee in partial-cone and 1,2-alternate
conformations. The procedure was the same as that employed for
synthesizing compounds 11bee, but starting from the appropriate
di(carboxylic acid) 17a or 19a. Yields, melting points, spectra, and
combustion analysis data for compounds 17bee and 19bee are
given in Supplementary data.
Fig. S9. Profile for competitive solvent extraction of AEMC into
chloroform by partial-cone, di-ionizable calix[4]arene-1,2-crown-4
ligands 16aee with eO(CH2)3C(O)Y side arms (page S23).
Fig. S10. Profile for competitive solvent extraction of AEMC into
chloroform by partial-cone, di-ionizable calix[4]arene-1,2-crown-4
ligands 17aee with eO(CH2)4C(O)Y side arms (page S23).
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.09.065.
4.3. Procedures for divalent metal ion extraction
Procedures for competitive alkaline earth metal cation extrac-
tion, single species extraction of Pb2þ, and single species extraction
of Hg2þ from aqueous solutions into chloroform have been reported
previously.10e14
References and notes
Since ligands 10d, 10e, 11b, 11d, and 11e were obtained as
monosodium salts, modified procedures were employed to remove
the Naþ before performing extractions with these ligands.
For competitive solvent extraction of AEMC. Into a capped, poly-
propylene, 15-mL centrifuge tube was placed 3.0 mL of 4.0 M
aqueous HCl and 3.0 mL of a 1.0 mM chloroform solution of the
ligand. The tube was vortexed with a Glas-Col Multi-Pulse Vortexer
for 30 min at room temperature and the tube was centrifuged for
10 min for phase separation with a BectoneDickinson Clay Adams
BrandÒ Centrifuge. A 2.5-mL portion of the organic phase was re-
moved and added to 2.5 mL of distilled water in a new, 15-mL
polypropylene centrifuge tube. The tube was vortexed for 10 min
and then centrifuged for 10 min. A 2.0-mL portion of the organic
phase was removed for use in the solvent extraction experiment.
For single species solvent extraction of Pb2þ. Into a capped, poly-
propylene,15-mL centrifuge tube was placed 3.0 mL of 4 M aqueous
HNO3 and 3.0 mL of a 0.50 mM chloroform solution of the ligand.
The tube was vortexed for 30 min and then centrifuged for 10 min.
A 2.5-mL portion of the organic phase was removed and added to
2.5 mL of distilled water in a new, 15-mL polypropylene centrifuge
tube. The tube was vortexed for 10 min and then centrifuged for
10 min. A 2.0-mL of the organic phase was removed for use in the
solvent extraction experiment. For single species solvent extraction of
Hg2þ. Into a capped, polypropylene, 15-mL centrifuge tube was
placed 4.0 mL of 4.0 M HNO3 and 4.0 mL of a 0.25 mM chloroform
solution of the ligand. The tube was vortexed for 30 min and then
centrifuged for 10 min. A 3.5-mL portion of the organic phase was
removed and added to 3.5 mL of distilled water. The tube was
vortexed for 10 min and centrifuged for 10 min. A 3.0-mL portion of
the organic phase was removed for use in the solvent extraction
experiment.
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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-FG02-90ER1446) for support of this
research.