Synthesis and metal ion extraction of calix[4]arene mono- and diacids with 2-methoxyethoxy pendant groups

Article abstract of DOI:10.1007/s10847-010-9892-3

A mono-ionizable calix[4]arene-based ligand with three 2-methoxyethoxy pendant groups is synthesized. A di-ionizable analogue with two 2-methoxyethoxy pendant groups is also prepared. Competitive solvent extractions of alkali metal cations and of alkaline

Full text of DOI:10.1007/s10847-010-9892-3

J Incl Phenom Macrocycl Chem (2011) 70:197–204
DOI 10.1007/s10847-010-9892-3
ORIGINAL ARTICLE
Synthesis and metal ion extraction of calix[4]arene
mono- and diacids with 2-methoxyethoxy pendant groups
•
Yanfei Yang Eun Kyung Lee Hui Zhou
•
•
•
Kazimierz Surowiec Richard A. Bartsch
Received: 11 August 2010 / Accepted: 14 October 2010 / Published online: 3 November 2010
Ó Springer Science+Business Media B.V. 2010
Abstract A mono-ionizable calix[4]arene-based ligand
with three 2-methoxyethoxy pendant groups is synthesized.
A di-ionizable analogue with two 2-methoxyethoxy pen-
dant groups is also prepared. Competitive solvent extrac-
tions of alkali metal cations and of alkaline earth metal
cations by these ligands are performed, as are single spe-
cies extractions of Hg2? and of Pb2?. The number of
proton-ionizable groups in the ligand is found to influence
the metal ion binding behavior.
calixarenes exhibit enhanced cation binding affinity and
selectivity compared to non-ionizable analogues, such as
calixarenes bearing ketone, ester or amide functions [8].
Previously, we have reported the synthesis and solvent
extraction study results of some mono-ionizable calix[4]-
arene-based ligands (Fig. 1). Compound 1 is a calix[4]ar-
ene carboxylic acid with three methoxy groups on the
lower rim [9]. Since methyl is small enough to rotate
through the central cavity of calix[4]arene, ligand 1 is
conformationally mobile. An NMR spectroscopic study of
ligand 1 and Li? revealed that the complex mainly adopted
a cone conformation. The conformationally rigid monoacid
2 in a locked cone conformation [10] has a better ‘‘preor-
ganized’’ structure for Li? complexation and exhibits high
selectivity for Li? over Na? and K?.
Keywords Mono-ionizable calixarene Á Di-ionizable
calixarene Á Ionic recognition Á Metal ion extraction Á
Solvent extraction
Introduction
Compared to butoxy groups, lower-rim 2-methoxyethoxy
pendant groups could provide additional binding sites and
influence the metal ion binding behavior of the ligand. In this
article, we describe the synthesis of tri(2-methoxyeth-
oxy)calix[4]arene mono(carboxylic acid) 3 (Fig. 2) and its
metal ion extraction properties towards alkali metal cations
(AMC) and alkaline earth metal cations (AEMC), as well as
Calixarenes have been widely utilized as building blocks
for synthesizing receptors for ions and neutral molecules
over the past 30 years [1, 2]. Some calixarene-based
ligands are among the most effective synthetic ionophores
for selective metal cation binding [3–5]. Incorporation of
proton-ionizable groups (PIGs) can improve metal ion
extraction efficiencies [6, 7]. The presence of PIGs elimi-
nates the need to transport the counter anion into the
organic phase by losing a proton upon formation of the
ligand–metal ion complex. Carboxylic acid groups were
the first acidic function to be attached to calix[4]arene. For
a recent review, see [1], pp. 154–158. Proton-ionizable
O
O
O
O
O
O
O
O
O
O
OH
OH
Y. Yang Á E. K. Lee Á H. Zhou Á K. Surowiec Á
R. A. Bartsch (&)
1
Department of Chemistry and Biochemistry,
Texas Tech University, Lubbock, TX 79409-1061, USA
e-mail: richard.bartsch@ttu.edu
2
Fig. 1 Structures of two calix[4]arene mono(carboxylic acids)
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J Incl Phenom Macrocycl Chem (2011) 70:197–204
as a white solid with mp 228–230 °C (Lit mp [11]:
234–235 °C). IR (deposit from CH2Cl2 solution on a NaCl
plate): 3305 (OH) cm-1. H NMR (CDCl3): d 3.43 (2d,
1
O
O
O
O
O
O
O
O
O
J = 13.5 Hz, 4H, ArCH2Ar), 4.22 (d, J = 13.5 Hz, 2H,
ArCH2Ar), 4.35 (d, J = 13.0 Hz, 2H, ArCH2Ar), 5.19 (s,
2H, OCH2Ar), 6.63–6.68 (m, 3H, ArH), 6.90 (t, J = 7.5 Hz,
1H, ArH), 6.96–7.01 (m, 4H, ArH), 7.02–7.05 (m, 2H, ArH),
7.10 (d, J = 7.5 Hz, 2H, ArH), 7.45–7.49 (m, 1H, ArH),
7.51–7.55 (m, 2H, ArH), 7.72–7.74 (m, 2H, ArH), 9.21
(s, 2H, OH), 9.56 (s, 1H, OH). 13C NMR (CDCl3): d 31.6,
31.8, 79.3, 120.9, 121.9, 126.3, 128.3, 128.4, 128.7, 128.8,
129.0, 129.4, 134.3, 135.5, 149.1, 150.8, 151.2.
O
O
O
O
OH
O
O
OH
O
OH
3
4
Fig. 2 Structures of calix[4]arene mono(carboxylic acid) 3 and
di(carboxylic acid) analogue 4
Hg2? and Pb2?. The di-ionizable analogue diacid 4 is also
prepared and solvent extractions of the same metal ion spe-
cies are performed. The extraction data are compared to
evaluate the influence of the number of proton-ionizable
groups in the ligand on its metal ion complexation behavior.
Synthesis of cone 25-benzyloxy-26,27,28-tris(2-
methoxyethoxy)calix[4]arene (7)
Compound 6 (0.50 g, 0.97 mmol) was dissolved in DMF
(50 mL). To the solution, NaH (0.28 g, 11.64 mmol) was
added. The mixture was stirred at room temperature for
0.5 h. A solution of 2-methoxyethyl tosylate (1.34 g,
5.82 mmol) in DMF (50 mL) was added dropwise. The
reaction was continued at room temperature for 4 days.
The mixture was poured into cold aqueous 10% HCl
(150 mL) and the solid was filtered. The filter cake was
washed with water (200 mL) and then dissolved in CH2Cl2
(50 mL). The organic solution was dried over MgSO4 and
the solvent was evaporated in vacuo to give the crude
product, which was purified by chromatography on silica
gel with hexanes-EtOAc (50:1–4:1 gradient) as eluent.
Compound 7 (0.32 g) was obtained in 47% yield as a white
solid with mp 92–94 °C. 1H NMR (CDCl3): d 3.08
(d, J = 14.0 Hz, 2H, ArCH2Ar), 3.15 (d, J = 14.0 Hz, 2H,
ArCH2Ar), 3.29 (s, 6H, OCH3), 3.41 (s, 3H, OCH3),
3.68–3.76 (m, 4H, OCH2CH2O), 3.83 (t, J = 5.0 Hz, 2H,
OCH2CH2O), 4.03–4.13 (m, 6H, OCH2CH2O), 4.36
(d, J = 13.0 Hz, 2H, ArCH2Ar), 4.48 (d, J = 13.0 Hz, 2H,
ArCH2Ar), 4.91 (s, 2H, OCH2Ar), 6.45–6.51 (m, 6H, ArH),
6.66 (t, J = 8.0 Hz, 2H, ArH), 6.71–6.76 (m, 4H, ArH),
7.31-7.38 (m, 3H, ArH), 7.43–7.47 (m, 2H, ArH). 13C
NMR (CDCl3): d 30.8, 30.9, 58.6, 58.7, 71.7, 71.9, 72.7,
73.1, 76.7, 122.2, 127.9, 128.0, 128.2, 128.4, 129.5, 134.5,
134.8, 135.4, 135.5, 137.8, 155.0, 155.8, 156.7. Calc. for
C44H48O7: C, 76.72%; H, 7.02%. Found: C, 76.47%; H,
7.17%.
Experimental
General
Reagents were purchased from commercial suppliers and
used directly, unless noted otherwise. Calix[4]arene (5)
was obtained from Eburon Organics International, Inc., of
Lubbock, TX. Acetonitrile (MeCN) was dried over CaH2
and distilled just before use. Tetrahydrofuran (THF) was
dried over sodium wire with benzophenone ketyl as indi-
cator and distilled just before use. Infrared spectra were
taken with a Perkin-Elmer 1600 FT-IR spectrophotometer
as deposits from CH2Cl2 solutions onto NaCl plates.
Absorptions are given in wavenumbers (cm-1). NMR
spectra were recorded with a Varian Unity Inova FT-500
spectrometer (500 MHz for 1H, 126 MHz for 13C) in
CDCl3 with TMS as the internal standard. Chemical shifts
(d) are expressed in ppm downfield from TMS and cou-
pling constant (J) values are given in Hz. Melting points
were determined with a Mel-Temp apparatus. Combustion
analysis was performed by Desert Analytics Laboratory
(now Columbia Analytical Services) of Tucson, AZ.
Synthesis of cone 25-benzyloxy-26,27,
28-trihydroxycalix[4]arene (6)
Synthesis of calix[4]arene monobenzyl ether 6 was per-
formed by adaptation of a literature procedure [11]. A slurry
of calix[4]arene (5) (2.12 g, 5.00 mmol) and NaOCH3
(0.32 g, 5.9 mmol) in MeCN (150 mL) was refluxed for
0.5 h before benzyl bromide (2.16 g, 12.60 mmol) was
added. The mixture was refluxed for an additional 8 h. The
solvent was removed in vacuo and the residue was recrys-
tallizedfrom CHCl3–MeOH to afford 6(1.54 g) in 58% yield
Synthesis of cone 25-hydroxy-26,27,
28-tris(2-methoxyethoxy)calix[4]arene (8)
Compound 7 (2.40 g, 3.48 mmol) was dissolved in THF
(30 mL) and 10% Pd/C (0.25 g) and absolute EtOH
(30 mL) were added. The hydrogenolysis was carried out
under 70 psi hydrogen pressure at room temperature
overnight with a Parr pressure reaction shaker apparatus.
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199
The catalyst was filtered and the filtrate was evaporated in
vacuo to give 8 (1.77 g, 2.96 mmol) in 85% yield as a
white solid with mp 125–128 °C. IR (deposit from CH2Cl2
with CH2Cl2 (2 9 20 mL). The combined organic layers
were washed with water (2 9 50 mL), dried over MgSO4,
and evaporated in vacuo to give 0.24 g (82%) of 3 as a
white solid with mp 44–46 °C. IR (deposit from CH2Cl2
solution on a NaCl plate): 3538 (OH) cm-1 1H NMR
.
(CDCl3): d 3.22 (d, J = 13.0 Hz, 2H, ArCH2Ar), 3.31 (d,
J = 14.0 Hz, 2H, ArCH2Ar), 3.45 (s, 6H, OCH3), 3.46
(s, 3H, OCH3), 3.76 (t, J = 5.0 Hz, 4H, OCH2CH2O),
3.94–4.04 (m, 4H, OCH2CH2O), 4.07–4.11 (m, 2H,
OCH2CH2O), 4.14–4.18 (m, 2H, OCH2CH2O), 4.41
(d, J = 14.0 Hz, 2H, ArCH2Ar), 4.50 (d, J = 14.0 Hz, 2H,
ArCH2Ar), 4.89 (s, 1H, OH), 6.38–6.45 (m, 6H, ArH), 6.77
(t, J = 8.0 Hz, 1H, ArH), 6.97 (t, J = 8.0 Hz, 1H, ArH),
7.10 (d, J = 8.0 Hz, 2H, ArH), 7.16 (d, J = 8.0 Hz, 2H,
ArH). 13C NMR (CDCl3): d 30.6, 30.7, 58.8, 58.9, 71.2,
71.6, 71.7, 74.4, 119.1, 123.2, 123.3, 127.9, 128.1, 128.4,
129.2, 130.6, 132.7, 133.5, 136.9, 153.2, 154.0, 156.6.
Calc. for C37H42O7: C, 74.22%; H, 7.07%. Found: C,
74.00%; H, 6.94%.
solution on a NaCl plate): 3423 (OH), 1757 (C=O) cm-1
.
1H NMR (CDCl3): d 3.21 (d, J = 13.0 Hz, 2H, ArCH2Ar),
3.26 (d, J = 13.0 Hz, 2H, ArCH2Ar), 3.34 (s, 3H, OCH3),
3.44 (s, 6H, OCH3), 3.66-3.71 (m, 2H, OCH2CH2O),
3.76–3.83 (m, 4H, OCH2CH2O), 3.86–3.91 (m, 2H,
OCH2CH2O), 4.05–4.10 (m, 2H, OCH2CH2O), 4.34
(t, J = 6.0 Hz, 2H, OCH2CH2O), 4.44 (d, J = 13.0 Hz,
2H, ArCH2Ar), 4.55 (d, J = 13.0 Hz, 2H, ArCH2Ar), 4.74
(s, 2H, OCH2), 6.39–6.43 (m, 4H, ArH), 6.48–6.51 (m, 2H,
ArH), 6.91 (t, J = 8.0 Hz, 1H, ArH), 6.99 (t, J = 8.0 Hz,
1H, ArH), 7.11–7.17 (m, 4H, ArH), 11.06 (s, 1H, COOH).
13C NMR (CDCl3): d 30.3, 30.6, 58.5, 58.8, 71.2, 71.3,
71.9, 73.7, 74.9, 123.0, 123.4, 124.3, 128.0, 128.5, 128.6,
129.3, 132.9, 133.8, 135.6, 136.2, 153.0, 155.2, 157.1,
170.7. Calc. for C39H44O9: C, 71.32%; H, 6.75%. Found:
C, 71.34%; H, 6.81%.
Synthesis of cone 25-(ethoxycarbonylmethoxy)-
26,27,28-tris(2-methoxyethoxy)calix[4]arene (9)
Synthesis of cone 25,27-bis(2-methoxyethoxy)-26,28-
A mixture of 8 (0.30 g, 0.50 mmol) and NaH (0.08 g,
2.50 mmol) in DMF (50 mL) was stirred under nitrogen at
room temperature for 1 h and ethyl bromoacetate (0.20 g,
1.10 mmol) was added. The mixture was stirred at 50 °C for
3 days. The mixture was poured into cold 10% aqueous HCl
(150 mL) and the solid was filtered. The solid was washed
with water (100 mL) and air dried. The crude product was
chromatographed on silica gel with hexanes-EtOAc
(20:1–2:1 gradient) to give monoester 9 (0.31 g) in 88%
yield as a white solid with mp 94-96 °C. IR (deposit from
di(benzyloxy)calix[4]arene (11)
A mixture of 10 [12] (5.00 g, 8.30 mmol) and NaH
(1.60 g, 66.20 mmol) in DMF (100 mL) was stirred under
nitrogen at room temperature for 30 min. A solution of 2-
methoxyethyl tosylate (7.61 g, 33.1 mmol) in DMF
(50 mL) was added dropwise. After reaction at room
temperature for 3 days, the mixture was poured into cold
aqueous 10% HCl and stirred for 30 min. The solid was
filtered and dissolved in CH2Cl2 (200 mL). The solution
was washed with water (2 9 100 mL), dried over MgSO4,
and evaporated in vacuo to give the crude product, which
was chromatographed on silica gel with CH2Cl2–hexanes
(1:1) as eluent to give 11 (4.90 g, 82%) as a white solid
with mp 158–160 °C. 1H NMR (CDCl3): d 3.08 (d,
J = 13.5 Hz, 4H, ArCH2Ar), 3.14 (s, 6H, CH3O), 3.60 (t,
J = 6.1 Hz, 4H, OCH2CH2O), 4.05 (t, J = 6.1 Hz, 4H,
OCH2CH2O), 4.38 (d, J = 13.4 Hz, 4H, ArCH2Ar), 4.88
(s, 4H, OCH2), 6.35 (d, J = 7.2 Hz, 4H, ArH), 6.37–6.44
(m, 2H, ArH), 6.70–6.79 (m, 2H, ArH), 6.85 (d, J =
7.4 Hz, 4H, ArH), 7.29–7.38 (m, 6H, ArH), 7.43–7.49
(m, 4H, ArH). 13C NMR (CDCl3): d 30.9, 58.5, 71.5, 72.5,
77.0, 122.2, 122.4, 127.8, 127.9, 128.2, 128.6, 129.3,
134.2, 135.8, 137.8, 154.8, 157.2. Calc. for C48H48O6: C,
79.97%; H, 6.71%. Found: C, 79.98%; H, 6.82%.
1
CH2Cl2 solution on NaCl plate): 1759 (C=O) cm-1. H
NMR (CDCl3): d 1.29 (t, J = 7.0 Hz, 3H, CH2CH3), 3.16 (d,
J = 14.0 Hz, 2H, ArCH2Ar), 3.20 (d, J = 14.0 Hz, 2H,
ArCH2Ar), 3.41 (s, 9H, OCH3), 3.80–3.90 (m, 6H, OCH2-
CH2O), 4.05–4.14 (m, 6H, OCH2CH2O), 4.22 (q, J =
7.0 Hz, 4H, OCH2CH3), 4.49 (d, J = 14.0 Hz, 2H,
ArCH2Ar), 4.68 (d, J = 14.0 Hz, 2H, ArCH2Ar), 4.73
(s, 2H, OCH2), 6.50–6.58 (m, 6H, ArH), 6.62-6.67 (m, 2H,
ArH), 6.71 (d, J = 8.0 Hz, 4H, ArH). 13C NMR (CDCl3): d
14.2, 30.7, 31.0, 58.6, 60.4, 71.0, 71.8, 71.9, 72.8, 73.2,
122.3, 122.6, 128.1, 128.2, 128.3, 128.5, 134.5, 134.7, 135.0,
135.3, 155.8, 156.0, 156.5, 170.2. Calc. for C41H48O9: C,
71.91%; H, 7.06%. Found: C, 71.99%; H, 7.14%.
Synthesis of cone 25-(carbonylmethoxy)-26,27,28-
tris(2-methoxyethoxy)calix[4]arene (3)
Synthesis of cone 25,27-bis(2-methoxyethoxy)-26,
A solution of 9 (0.31 g, 0.44 mmol), 25 mL of 10%
aqueous Me4NOH and 25 mL of THF was refluxed for 24
h. After evaporation of the THF in vacuo, 20 mL of 6 N
HCl was added to the residue. The mixture was extracted
28-dihydroxycalix[4]arene (12)
Compound 11 (4.85 g, 6.70 mmol) was mixed with 10%
Pd/C (1.00 g), MeOH (150 mL) and THF (50 mL) in a
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glass pressure reaction vessel. The hydrogenolysis was
carried out under 70 psi of hydrogen pressure at room
temperature overnight with a Parr pressure reaction shaker
apparatus. The catalyst was filtered and the filtrate was
evaporated in vacuo to give 12 (3.56 g, 99%) as a white
solid with mp 218–220 °C. IR (deposit from CH2Cl2
were washed with water (2 9 100 mL), dried over MgSO4,
and evaporated in vacuo to give the crude product which
recrystallized from CH2Cl2–MeOH to give 4 (2.90 g, 90%)
as a white solid with mp 240–242 °C. IR (deposit from
CH2Cl2 solution on NaCl plate): 3400–2900 (CO2H), 1758,
1736 (C=O) cm-1 1H NMR (CDCl3): d 3.27 (d, J =
.
solution on a NaCl plate): 3356 (OH) cm-1
.
1H NMR
13.3 Hz, 4H, ArCH2Ar), 3.47 (s, 6H, CH3O), 3.70–3.83
(m, 4H, OCH2CH2O), 3.92–4.04 (m, 4H, OCH2CH2O),
4.56 (d, J = 13.2 Hz, 4H, ArCH2Ar), 4.80 (s, 4H, OCH2),
6.36–6.49 (m, 6H, ArH), 7.01 (t, J = 7.5 Hz, 2H, ArH),
(CDCl3): d 3.36 (d, J = 13.1 Hz, 4H, ArCH2Ar), 3.56 (s,
6H, CH3O), 3.86–3.96 (m, 4H, OCH2CH2O),
4.12–4.22 (m, 4H, OCH2CH2O), 4.40 (d, J = 13.1 Hz,
4H, ArCH2Ar), 6.65 (t, J = 7.4 Hz, 2H, ArH), 6.72
(t, J = 7.6 Hz, 2H, ArH), 6.89 (d, J = 7.6 Hz, 4H, ArH),
7.05 (d, J = 7.4 Hz, 4H, ArH), 7.83 (s, 2H, OH). 13C NMR
(CDCl3): d 31.2, 59.3, 71.4, 75.5, 118.9, 125.3, 128.2,
128.4, 128.9, 133.4, 151.9, 153.2. Calc. for C34H36O6: C,
75.53%; H, 6.71%. Found: C, 75.08%; H, 6.62%.
7.17 (d, J = 7.4 Hz, 4H, ArH), 9.99 (br s, 2H, CO2H). 13
C
NMR (CDCl3): d 30.4, 58.8, 70.9, 72.2, 75.8, 123.7, 124.3,
128.5, 129.3, 133.0, 135.3, 135.5, 152.3, 156.1, 171.0.
Analysis calculated for C38H40O10: C, 69.50%; H, 6.14%.
Found: C, 69.44% ; H, 6.16%.
Procedure for competitive extraction of alkali metal
cations
Synthesis of cone 25,27-bis(ethoxycarbonylmethoxy)-
26,28-bis(2-methoxyethoxy)calix[4]arene (13)
An aqueous solution of the alkali metal chlorides with
LiOH or HCl for pH adjustment (2.0 mL, 10.0 mM in each
alkali metal cation species) and 2.0 mL of a 1.0 mM
solution of the ligand in chloroform in a capped, poly-
propylene, 15-mL centrifuge tube was vortexed for 10 min
with a Glas-Col Multi-Pulse Vortex Mixer. The tube was
centrifuged with a Clay Adams Compact II Centrifuge for
10 min to promote phase separation. A 1.5-mL portion of
the organic phase was removed and added to 3.0 mL of
0.10 M HCl in a new 15-mL polypropylene centrifuge
tube. The tube was vortexed for 10 min and centrifuged for
10 min. The aqueous phase from this stripping step was
diluted to 10.0 mL with deionized water and the alkali
metal cation concentrations were determined with a Dionex
DX-120 ion chromatograph with a CS12A column with
conductivity detection and membrane suppression (Dionex
Model CMMS-II). The pH of the aqueous phase from the
initial extraction step was determined with a Fisher Acc-
umet AR25 pH meter with a Corning 476157 combination
pH electrode.
A mixture of 12 (3.50 g, 6.50 mmol) and NaH (0.62 g,
25.90 mmol) in DMF (100 mL) was stirred under nitrogen
at room temperature for 0.5 h. Ethyl bromoacetate
(1.58 mL, 14.20 mmol) was added dropwise. After reac-
tion at room temperature overnight, the mixture was poured
into cold aqueous 10% HCl and stirred for 0.5 h. The
precipitate was filtered and the filter cake was dissolved in
CH2Cl2 (200 mL). The organic phase was washed with
water (2 9 100 mL), dried over MgSO4, and evaporated in
vacuo to produce the crude product which was recrystal-
lized from CH2Cl2–MeOH giving 13 (3.69 g, 80%) as a
white solid with mp 121–123 °C. IR (deposit from CH2Cl2
1
solution on a NaCl plate): 1758 (C=O) cm-1. H NMR
(CDCl3): d 1.29 (t, J = 7.1 Hz, 6H, OCH2CH3), 3.19
(d, J = 13.5 Hz, 4H, ArCH2Ar), 3.40 (s, 6H, CH3O), 3.81
(t, J = 5.1 Hz, 4H, OCH2CH2O), 4.09 (t, J = 5.1 Hz, 4H,
OCH2CH2O), 4.22 (q, J = 7.1 Hz, 4H, OCH2CH3), 4.72
(d, J = 13.4 Hz, 4H, ArCH2Ar), 4.74 (s, 4H, OCH2), 6.50
(s, 6H, ArH), 6.65–6.73 (m, 2H, ArH), 6.77 (d, J = 7.3 Hz,
4H, ArH). 13C NMR (CDCl3): d 31.0, 58.6, 60.4, 70.9,
72.0, 73.3, 122.4, 122.6, 128.1, 128.6, 134.4, 135.2, 155.9,
156.0, 170.3. Calc. for C42H48O10: C, 70.77%; H, 6.79%.
Found: C, 70.40%; H, 6.72%.
Procedure for competitive extraction of alkaline earth
metal cations
The procedure for competitive extraction of alkaline earth
metal cations was the same as that reported previously
[13].
Synthesis of cone 25,27-bis(carboxymethoxy)-26,28-
bis(2-methoxyethoxy)calix[4]arene (4)
A solution of 13 (3.50 g, 4.90 mmol), THF (200 mL), 25%
aqueous Me4NOH (100 mL), and water (50 mL) was
refluxed overnight. The THF was evaporated in vacuo and
the resulting aqueous solution was cooled in an ice-bath and
acidified with 6 N HCl. The mixture was extracted with
CH2Cl2 (2 9 100 mL). The combined organic extracts
Procedure for single species extraction of Pb2?
The procedure for single species extraction of Pb2? was the
same as that reportedpreviously [13], except that a Shimadzu
AA-6300 atomic absorption spectrophotometer was utilized.
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Procedure for single species extraction of Hg2?
201
[4]arene 7 in 47% yield. Catalytic hydrogenolysis of 7
over Pd/C in EtOH/THF gave the monohydroxy tri(2-
methoxyethoxy)calix[4]arene 8 in 85% yield. Monoester 9
was obtained in 88% yield by reaction of 8 with NaH and
ethyl bromoacetate in DMF. Subsequent hydrolysis of 9
with Me4NOH in aqueous THF gave an 82% yield of
mono(carboxylic acid) 3.
An aqueous solution (3.0 mL) of 0.25 mM Hg(NO3)2 with
Me4NOH or HNO3 for pH adjustment and 3.0 mL of
0.25 mM ligand solution in chloroform in a capped 15-mL
polypropylene centrifuge tube were vortexed for 10 min at
room temperature and then centrifuged for 10 min at room
temperature. A 0.50-ml portion of the aqueous phase was
removed and diluted to 5.0 with deionized water. The pH
of the aqueous phase from the initial extraction was mea-
sured. A 1.0-ml portion of the diluted sample was added to
100 mL of 1.0 N H2SO4 in a glass reaction bottle, which
was then connected to a Shimadzu MVU-1A mercury
vaporizer unit. The Hg2? in the sample was reduced using
5.0 mL of SnCl2 solution prepared by dissolving 20 g of
SnCl2ÁH2O in 40 mL of conc HCl and diluting the solution
to 200 mL with deionized water. The reduced mercury
vapor was then pumped through a flow cell and the mer-
cury concentration was measured at 253.6 nm with a Shi-
madzu AA-6300 spectrophotometer. The vapor was then
pumped to a waste receptacle, where it was re-oxidized
with a 0.5% solution of KMnO4 in 5% H2SO4.
Di(2-methoxyethoxy)calix[4]arene di(carboxylic acid) 4
was prepared using a similar synthetic strategy (Scheme 2).
Although it was reported that 25,27-bis(2-methoxyethoxy)-
calix[4]arene (12) could be obtained in 43% yield by
reaction of calix[4]arene (5) with 2-methoxyethyl tosylate
in refluxing MeCN with 2.0 equivalents of K2CO3 as the
base [14], in our hands, this reaction produced a mixture of
mono-, di- and tetra-substituted products. Therefore, an
alternate pathway was adopted. A mixture of calix[4]arene
5, benzyl bromide, K2CO3, and MeCN gave 25,27-dib-
enzyloxycalix[4]arene 10 in 92% yield. Compound 10 was
reacted with NaH and an excess of 2-methoxyethyl tosylate
in DMF to give tetraether 11 in 82% yield. Catalytic
hydrogenolysis of 11 cleaved the two benzyl groups to give
25,27-bis(2-methoxyethoxy)-26,28-dihydroxycalix[4]arene
12 quantitatively. Reaction of 12 with NaH and an excess
of BrCH2CO2Et in DMF provided diester 13 in 80% yield.
Subsequent hydrolysis of 13 with 10% aqueous NMe4OH
gave a 90% yield of di(carboxylic acid) 4.
Results and discussion
Synthesis of the tri(2-methoxyethoxy)calix[4]arene mono
(carboxylic acid) 3 is depicted in Scheme 1. Monobenzy-
lation of calix[4]arene (5) was performed by modification
of a reported procedure [11] to produce the mono-
benzyloxycalix[4]arene 6 in 58% yield. Compound 6 was
reacted with NaH and 2-methoxyethyl tosylate in DMF
to give the monobenzylated tris(2-methoxyethoxy)calix
Structures of new calix[4]arene ligands 3 and 4 and their
1
synthetic precursors were verified by H and 13C NMR
spectroscopy, IR spectrophotometry, and combustion
1
analysis. By H NMR spectroscopy, the cone conforma-
tions of the calix[4]arene frameworks were confirmed.
For competitive solvent extraction of AMC, aqueous
solutions containing Li?, Na?, K?, Rb?, and Cs?
b
O
O
O
O
O
Bn
OH
O
OH
OH
OH
OH
OH
OH
O
O
Bn
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
e
c
d
O
O
O
OH
O
O
O
Scheme 1 Synthesis of tri(methoxyethoxy)calix[4]arene mono(carboxylic acid) 3. Reagents and conditions: a BnBr, NaOCH3, MeCN, reflux;
b CH3OCH2CH2OTs, NaH, DMF, r.t.; c H2, Pd/C, EtOH/THF, r.t.; d BrCH2CO2Et, NaH, DMF, r.t.; e Me4NOH, aqueous THF, reflux
123

202
J Incl Phenom Macrocycl Chem (2011) 70:197–204
Scheme 2 Synthesis of
di(methoxyethoxy)calix[4]arene
di(carboxylic acid) 4. Reagents
and conditions: a BnBr, K2CO3,
MeCN, reflux;
b MeOCH2CH2OTs, NaH,
DMF, r.t.; c H2, Pd/C, THF/
MeOH; d BrCH2CO2Et, NaH,
DMF, r.t.; e 10% aqueous
NMe4OH, THF, reflux
b
O
O
O
O
Bn
Bn
OH
O
OH
O
OH
OH
OH
OH
O
O
Bn
Bn
O
O
O
O
OH
O
O
O
O
O
OH
e
O
O
O
c
d
O
O
O
O
O
O
O
O
O
OH
O
OH
(10.0 mM in each) chlorides were extracted with 1.0 mM
solutions of ligands 3 and 4 in chloroform. Plots of metal
ion loadings of the organic phase versus the equilibrium pH
of the aqueous phase are presented in Fig. 3. Note that the
theoretical total metal loadings for ligands 3 and 4 are
different. For diacid 4, the maximal total loading for
monovalent cations is 200%, but 100% is the maximal total
loading for monoacid 3. In low pH regions, no deproto-
nation occurs for the proton-ionizable groups in ligands 3
and 4 and the metal ion loading is negligible. This shows
that the non-ionized forms of the ligands are ineffective
extractants. Observed maximal total AMC loadings for
ligands 3 and 4 are 80 and 160%, respectively. This sug-
gests that the two carboxylic acid groups in ligand 4 are
operating independently in AMC extraction.
The two ligands have very similar binding behavior
towards AMC. Both ligands show an AMC extraction order
of Na?[ Li? [[ K?, Rb?, Cs? at maximal loading.
Extractions of Na? and Li? by the monoacid 3 take place
concurrently. On the other hand, diacid 4 exhibits high
selectivity for Na? extraction at weakly acidic pH until the
Li? extraction commences at neutral pH.
Fig. 3 Percent metal loading of
the organic phase versus the
equilibrium pH of the aqueous
200
b
a
100
180
160
140
120
100
80
phase for competitive solvent
extraction of alkali metal
cations into chloroform by
80
a tri(2-
methoxyethoxy)calix[4]arene
mono(carboxylic acid) 3 and
b di(2-methoxyethoxy)-
60
calix[4]arene di(carboxylic
acid) 4. (square Li?, circle Na?,
triangle K?, inverted triangle
Rb?, diamond Cs)
40
60
20
0
40
20
0
0
2
4
6
8
10
12
0
2
4
6
8
10
12
pH
pH
123

J Incl Phenom Macrocycl Chem (2011) 70:197–204
203
Fig. 4 Percent metal loading of
the organic phase versus the
equilibrium pH of the aqueous
phase for competitive solvent
extraction of alkaline earth
metal cations into chloroform
by a tri(2-methoxyethoxy)
calix[4]arene mono
a
b
100
80
60
40
20
0
(carboxylic acid) 3 and
b di(2-methoxyethoxy)-
calix[4]arene di(carboxylic
acid) 4. (square Mg2?, circle
Ca2?, triangle Sr2?, inverted
triangle Ba2?
)
0
2
4
6
8
10
12 0
pH
2
4
6
8
10
Aqueous solutions containing Mg2?, Ca2?, Sr2?, and
Ba2? (2.0 mM in each) chlorides were extracted with
1.0 mM solutions of ligands 3 and 4 in chloroform. For the
competitive AEMC extractions, plots of metal loading of
the organic phase versus the equilibrium pH of the aqueous
phase are presented in Fig. 4.
100
80
60
40
20
0
The AEMC extraction results for the two ligands is quite
different. As is readily apparent, monoacid 3 is an inef-
fective extractant toward all of the AEMC species. Diacid
4, on the other hand, shows appreciable AEMC extraction
at alkaline pHs. The AEMC extraction selectivity order for
diacid 4 is Sr2? [ Ca2? [ Ba2? [ Mg2?, with maximal
metal loading near 80% under the most alkaline conditions
employed. The marked difference in AEMC extraction
efficiency is readily understood when the matching
between the charges in the ionized ligand and the AEMC
are considered. When ionized, ligand 4 produces a dianion
that can form an electroneutral extraction complex with the
divalent metal ion. Formation of an electroneutral extrac-
tion complex for ligand 3 would require an unfavorable 2:1
(ionized ligand:divalent metal ion) stoichiometry.
0
2
4
6
8
pH
Fig. 5 Percent metal loading of the organic phase versus the
equilibrium pH of the aqueous phase for single species solvent
extraction of Pb2? into chloroform by a tri(2-methoxyethoxy)-
calix[4]arene mono(carboxylic acid) 3 (filled squares) and b di(2-
methoxyethoxy)calix[4]arene di(carboxylic acid) 4 (open circles)
Aqueous solutions of Pb2? (1.0 mM) nitrate were
extracted with 0.50 mM solutions of ligands 3 and 4 in
chloroform. Plots of metal loadings of the organic phase
versus the equilibrium pH of the aqueous phase by ligand 3
(closed squares) and 4 (open circles) are presented in
Fig. 5. The single species extraction results for the two
ligands are again strikingly different. Diacid 4 is a very
effective extractant for Pb2? from acidic solutions with a
maximal loading greater than 90%. In contrast, monoacid 3
is a poor extractant for the Pb2? with a maximal loading of
only about 10%.
Aqueous solutions of Hg2? (0.25 mM) nitrate were
extracted with 0.25 mM solutions of ligands 3 and 4 in
chloroform. Plots of metal loadings of the organic phase
versus the equilibrium pH of the aqueous phase by ligands
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J Incl Phenom Macrocycl Chem (2011) 70:197–204
Acknowledgments We thank the Division of Chemical Sciences,
Geosciences and Biosciences of the Office of Basic Energy Sciences
of the U.S. Department of Energy (Grant DE-FG02-90ER14416) for
support of this research.
100
80
60
40
20
0
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.
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123