Di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 ligands: synthesis and alkaline earth metal cation extraction

Article abstract of DOI:10.1016/j.tet.2009.06.004

A series of di-ionizable calix[4]arene-1,3-crown-4 compounds has been synthesized. The ionizable groups are oxyacetic acid and N-(X)sulfonyl oxyacetamide groups with X=methyl, phenyl, 4-nitrophenyl and trifluoromethyl, which 'tunes' the acidity of the latter. The efficiency and selectivity of these novel ligands are assessed with competitive solvent extractions of alkaline earth metal cations from aqueous solutions into chloroform. The results are compared with those reported previously for calix[4]arene-crown analogues with crown-6 and crown-5 rings.

Full text of DOI:10.1016/j.tet.2009.06.004

Tetrahedron 65 (2009) 5893–5898
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 ligands: synthesis
and alkaline earth metal cation extraction
*
Xiaodong Liu, Kazimierz Surowiec, 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:
Received 5 May 2009
Received in revised form 29 May 2009
Accepted 2 June 2009
Available online 10 June 2009
A series of di-ionizable calix[4]arene-1,3-crown-4 compounds has been synthesized. The ionizable
groups are oxyacetic acid and N-(X)sulfonyl oxyacetamide groups with X¼methyl, phenyl, 4-nitrophenyl
and trifluoromethyl, which ‘tunes’ the acidity of the latter. The efficiency and selectivity of these novel
ligands are assessed with competitive solvent extractions of alkaline earth metal cations from aqueous
solutions into chloroform. The results are compared with those reported previously for calix[4]arene-
crown analogues with crown-6 and crown-5 rings.
Keywords:
Calixarenes
Ó 2009 Elsevier Ltd. All rights reserved.
Crown ethers
Ionic recognition
Solvent extraction
1. Introduction
Previously we reported the synthesis and alkaline earth metal
ion extraction behavior of di-ionizable p-tert-butylcalix[4]arene-
In calixarene-crown ethers, also called calixcrowns, a calixarene
scaffold is combined with a crown ether unit connecting two
phenolic oxygens of the former with a polyether chain.1–6 Most
common are calix[4]arene-1,3-crown compounds in which a cal-
ix[4]arene platform is connected with a polyether fragment that
bridges two distal phenolic oxygens. The first example of this ligand
family, p-tert-butylcalix[4]arene-1,3-crown-6, was reported by
Ungaro and co-workers in 1983.7 In calix[4]arene-crown com-
pounds, depending on the synthetic conditions used, the bridging
polyether unit can lock the calixarene framework in cone, partial
cone, or 1,3-alternate conformations.
Of particular interest to our metal ion separations research pro-
gram are calix[4]arene-crown compounds with two acidic pendant
groups attached to the remaining phenolic oxygens. Such ligands
provide efficient extraction of divalent metal ions from aqueous
solutions into organic diluents.8–17 The extraction proceeds by an
ion-exchange mechanism to form an electroneutral di-ionized cal-
ixcrown-divalent metal ion complex in the organic phase, thereby
avoiding the need for concomitant transfer of a hydrophilic anion
from the aqueous phase.
1,3-crown-6 ligands in the cone (3a–e), partial cone (6a–e), and 1,3-
alternate (9a–e) conformations.8 In these series, the pendant
di-ionizable groups included oxyacetic acid groups and
N-(X)sulfonyl oxyacetamide groups. In the latter, variation of the
electron-withdrawing ability of X ‘tunes’ the acidity of the ligand.
For competitive solvent extraction of four alkaline earth metal
cation species from aqueous solutions into chloroform, the cone
conformers 3a–e exhibited very high Ba2þ selectivity with high
extraction efficiency. In the cone conformation, one ionized group
is positioned above and the other below a divalent metal ion
complexed within the polyether cavity. For a given ionizable group,
the extraction selectivity decreased in the order: cone>1,3-alter-
nate>partial cone.
To probe the influence of decreasing the crown ether ring size,
an analogous series of di-ionizable p-tert-butylcalix[4]arene-1,3-
crown-5 ligands in the cone (2a–e), partial cone (5a–e), and 1,3-
alternate (8a–e) conformations were prepared.9 For competitive
extraction of four alkaline earth metal cation species from aqueous
solutions into chloroform by the dicarboxylic acid ligands 2a, 5a,
and 8a, the partial cone conformer 5a was found to be the most
effective extractant with a very high selectivity for Ba2þ. Of the
three ligands, cone conformer 2a gave the poorest extraction se-
lectivity and extracted approximately the same amounts of Sr2þ
The initial example of such a di-ionizable calixcrown compound,
cone p-tert-butylcalix[4]arene-1,3-crown-5 dicarboxylic acid 2a
(Fig. 1) was reported by Ungaro and Pochini in 1984.18
and Ba2þ
.
In light of this puzzling difference in alkaline earth metal cation
extraction selectivity when the crown ring size was decreased from
crown-6 to crown-5, we envisioned series of di-ionizable p-tert-
* Corresponding author. Tel.: þ1 806 742 3069; fax: þ1 806 742 1289.
E-mail address: richard.bartsch@ttu.edu (R.A. Bartsch).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.004

5894
X. Liu et al. / Tetrahedron 65 (2009) 5893–5898
n
1
1
2
2
O
O
O
n
O
O
3
3
Z
O
O
Z
O
Z
a
b
-OH
Cone
-NHSO2Me
c
d
e
-NHSO2Ph
Z
O
4
5
1
2
-NHSO2C6H4-4-NO2
-NHSO2CF3
O
6
3
O
O
O
O
O
O
Z
n
Partial-Cone
Z
Z
7
8
9
1
2
3
O
O
O
O
O
O
n
O
O
1,3-Alternate
Figure 1. Structures of di-ionizable p-tert-butylcalix[4]arene-1,3-crown compounds.
butylcalix[4]arene-1,3-crown-4 ligands. We now report the results
of these synthetic endeavors and the alkaline earth metal cation
extraction behavior of the resultant ligands.
that is two widely spaced doublets at d 4.16–4.29 and 3.10–3.24 for
the exo- and endo-geminal protons, respectively.
The envisioned synthetic route to di-ionizable p-tert-butylca-
lix[4]arene-1,3-crown-4 analogs 7a–e in the 1,3-alternate
conformations is presented in Scheme 2. Reaction of p-tert-butylca-
lix[4]arene-1,3-crown-4 with KH and ethyl bromoacetate in THF at
room temperature gave an 80% yield of diester 14. Hydrolysis with
Me4NOH in aqueous THF at reflux produced a near quantitative yield
of di(carboxylic acid) 7a. However, afterheating di(carboxylic acid) 7a
with oxalyl chloride in benzene at reflux for 5 h there was no evi-
dence (shift in the C]O absorption in the IR spectrum) for formation
of di(acid chloride) 15. Increasing the reaction time to 15 h gave the
same result. Attention was then shifted to the use of thionyl chloride
as reactant and solvent. It was found that heating 7a in thionyl
chloride (5 mL/g of 7a) at reflux for 24 h gave a clean conversion into
di(acid chloride) 15, as shown by the shift of the C]O absorption
from 1767 cmꢀ1 to 1815 cmꢀ1. The attempt to convert the crude 15
into 7b using the conditions that were successfully applied to the
cone di(acid chloride) 13, gave no reaction. Heating of the mixture of
15, NaH, and CH3SO2NH2 in THF at reflux for 24 and 48 h also pro-
duced no reaction. Likewise, substituting CF3SO2NH2 for CH3SO2NH2
gave no reaction. Apparently the flanking tert-butyl groups in the 1,3-
alternate di(acid chloride) 15 provide steric hindrance to attack by
XSO2NHꢀNaþ at the carbonyl carbon.
2. Results and discussion
2.1. Synthesis of new di-ionizable calix[4]arene-1,3-
crown-4 ligands
The synthesis of cone di-ionizable p-tert-butylcalix[4]arene-1,3-
crown-4 compounds 1a–e was performed as depicted in Scheme 1.
Using the procedure of Shinkai and co-workers,19 p-tert-butylca-
lix[4]arene (10) was reacted with triethylene glycol ditosylate and
Na2CO3 in MeCN to provide p-tert-butylcalix[4]arene-1,2-crown-4
(11). Reaction of 11 with NaH and ethyl bromoacetate in THF at room
temperature gave the diester 12 in 80% yield. The diester was hy-
drolyzed with Me4NOH in refluxing aqueous THF to produce di-
(carboxylic acid) 1a in 99% yield. Treatment of 1a with oxalyl chloride
in refluxing benzene gave the corresponding di(acid chloride) 13,
which was reacted with the sodium salt forms of commercially
available sulfonamides in THF to form ligands 1b–e in 70–97% yields.
The cone conformation of di-ionizable p-tert-butylcalix[4]ar-
ene-1,3-crown-4 ligands 1a–e was established by their 1H and 13C
NMR spectra. There were no peaks between 35 and 40 ppm in the
13C NMR spectra for the five compounds, showing that all four
benzene rings have syn arrangements. In the 1H NMR spectra, the
methylene bridge (ArCH2Ar) protons exhibited a typical AX pattern,
The 1,3-alternate conformation of di(carboxylic acid) 7a was
verified by its 1H and 13C NMR spectra. Both the aromatic and tert-
butyl protons gave two singlets that are closer together than those
for the cone analogue 1a. The methylene bridge (ArCH2Ar) protons

X. Liu et al. / Tetrahedron 65 (2009) 5893–5898
5895
b
a
O
O
O
OH
O
O
O
OH
O
O
O
O
OH
H
OH
H
O
O
O
EtO
10
O
11
OEt
12
c
d
e
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
XO2SHN
O
O
O
NHSO2X
O
O
O
O
Cl
O
HO
Cl
OH
13
1a
X
1b Me
Ph
1c
C6H4-4-NO2
CF3
1d
1e
Scheme 1. Synthesis of cone di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 ligands 1a–e. (a) Na2CO3, TsO(CH2CH2O)3Ts, MeCN, reflux, 7 d; (b) NaH, BrCH2CO2Et, THF, rt, 12 h;
(c) 10% aq Me4NOH, THF, reflux, 12 h; (d) oxalyl chloride, C6H6, reflux, 5 h; (e) NaH, NH2SO2X, rt, 12 h, except 3 h when X¼C6H4–4-NO2.
are two closely spaced doublets (AB pattern), which correlate with
anti-oriented bridge carbons ( w39 ppm).
In view of our inability to obtain the 1,3-alternate di-[N-(X)sul-
fonyl carbamoyl] ligands 7b–e, the objective to develop a synthetic
route to di-ionizable partial cone ligands 4a–e was abandoned.
of the new di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 li-
gands in chloroform were performed to probe their propensity
for extraction of these divalent metal ions.
d
A plot of the alkaline earth metal cation loading of the organic
phase versus the pH of the aqueous phase for cone di(carboxylic
acid) 1a is presented in Figure 2c. For comparison, data reported
previously for analogues with crown-6 and crown-5 rings are
shown in Figures 2a and 2b, respectively. A marked effect of
the crown ring size of the dicarboxylic acid extractant on the al-
kaline earth metal cation extraction behavior is readily evident.
Ligand 3a efficiently and selectively extracts Ba2þ. With a decrease
in ring size to crown-5, extraction efficiency remains high, but the
2.2. Competitive solvent extraction of alkaline earth metal
cations by di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4
ligands 1a–e and 7a
Competitive solvent extractions of aqueous alkaline earth
metal cation solutions (2.0 mM in each) by 1.0 mM solutions
OH
OEt
HO
EtO
O
O
O
O
O
O
O
O
a
b
O
O
O
O
O
O
O
O
O
O
O
O
H
H
O
O
11
7a
14
c
NHSO2X
Cl
XO2SHN
Cl
O
O
O
O
d
O
O
O
O
O
O
O
O
O
O
O
O
16
15
Scheme 2. Synthesis of 1,3-alternate di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 ligand 7a and attempted synthesis of 16. (a) KH, BrCH2CO2Et, THF, rt, 12 h; (b) 10% aq
Me4NOH, THF, reflux, 12 h; (c) thionyl chloride, neat, reflux, 24 h; (d) NaH, NH2SO2X, rt and reflux.

5896
X. Liu et al. / Tetrahedron 65 (2009) 5893–5898
alternate dicarboxylic acid 7a was available. A plot of metal cation
100
(a)
(b)
(c)
loading of the chloroform phase versus the equilibrium pH of the
aqueous phase is shown in Figure 4. Comparison of the extraction
profile for 7a with that for cone analogue 1a (Fig. 2c) reveals similar
weak extraction of alkaline earth metal cations. However, the
extraction selectivities are very different. Whereas the cone con-
former extracts Mg2þ best, the 1,3-alternate analogue 7a prefer-
entially extracts Ba2þ into the organic phase. Since the crown-4 ring
is too small to accommodate Ba2þ, this suggests that in 7a it is
complexed between the two carboxylate groups near to two of the
Mg2+
Ca2+
Sr2+
80
60
40
20
0
Ba2+
aromatic rings where there is the possibility of metal ion–
p in-
teractions21 with the softest alkaline earth metal cation in the
series.
100
Mg
Ca
90
Sr
Ba
80
70
60
50
40
30
20
10
0
2
4
6
8 10 12
2
4
6
pH
8 10 12
2
4 6 8 10 12
Figure 2. Percent metal loading versus the equilibrium pH of the aqueous phase for
competitive solvent extraction of alkaline earth metal cations into chloroform by cone
p-tert-butylcalix[4]-arene-1,3-crown ethers: (a) crown-6, 3a; (b) crown-5, 2a; and (c)
crown -4, 1a. Data for 3a and 2a taken from Refs. 8 and 9, respectively.
selectivity now is for Sr2þ and Ba2þ in approximately equal
amounts. With further contraction of the ring size to crown-4, the
extraction efficiency plummets with weak selectivity for Mg2þ. This
sensitivity of the selectivity to ring size variation is consistent with
complexation of the divalent metal ion within the polyether ring.
Plots of metal loading versus the equilibrium pH of the aqueous
phase for competitive solvent extraction of alkaline earth metal
cations into chloroform by cone p-tert-butylcalix[4]arene-1,3-
crown-4 di[N-(X)-sulfonyl carbamoyl] ligands 1b–e are presented
in Figure 3. The metal ion extraction efficiency increases as the
electron-withdrawing ability of X is enhanced in the order:
Me<Ph<C6H4–4-NO2<CF3.20 Selectivity for the smaller alkaline
earth metal cations is consistent with their complexation within
the polyether cavity.
3
4
5
6
pH
7
8
9
Figure 4. Percent metal loading versus the equilibrium pH of the aqueous phase for
competitive solvent extraction of alkaline earth metal cations into chloroform by 1,3-
alternate p-tert-butylcalix[4]-arene-1,3-crown-4 di(carboxylic acid) 7a.
3. Experimental
3.1. General
For the di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 li-
gands locked in other than a cone conformation, only the 1,3-
Melting points were determined with a Mel-Temp melting point
apparatus and are uncorrected. Infrared (IR) spectra were recorded
with a Perkin-Elmer Model 1600 FT-IR spectrophotometer as de-
posits from CH2Cl2 solution on a NaCl plate. 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) in CDCl3 with Me4Si as
100
(a)
(b)
(c)
(d)
Mg2+
Ca2+
Sr2+
80
60
40
20
0
internal standard. Chemical shifts (d) are given in parts per million
Ba2+
downfield from TMS and coupling constants (J) values are in hertz.
Elemental analysis was performed by Desert Analytics Laboratory
of Tucson, Arizona.
Reagents from commercial sources were 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 a indicator and distilled just
before use.
p-tert-Butylcalix[4]arene-1,3-crown-4 (11) was prepared by
a reported procedure.19
For use in the metal ion extractions, reagent-grade chloroform
was washed with an equal volume of DI water to remove the sta-
bilizing ethanol and stored in the dark. Vortexing and centrifugation
of two-phase extraction mixtures were performed with a Glas-Col
Multi-Pulse vortexer and a Becton-Dickinson Clay Adams BrandÒ
centrifuge, respectively. The pH of the aqueous phase for an ex-
traction experiment was measured with a Fisher Accumet AR25 pH
meter with a Corning 476157 combination pH electrode. For
4 6 8 1012
2
4
6
8 1012
2
4
6
8 1012
2 4 6 8 1012
2
pH
Figure 3. Percent metal loading versus the equilibrium pH of the aqueous phase for
competitive solvent extraction of alkaline earth metal cations into chloroform by cone
p-tert-butylcalix[4]-arene-1,3-crown-4 di-[N-(X)sulfonyl carbamoyl] ligands 1b–e: (a)
X¼Me, 1b; (b) X¼Ph, 1c; (c) X¼C6H4–4-NO2, 1d; and (d) X¼CF3, 1e.

X. Liu et al. / Tetrahedron 65 (2009) 5893–5898
5897
determination of alkaline earth metal cation concentrations a Dio-
nex DX-120 ion chromatograph with a CS12A column with con-
ductivity detection and membrane suppression (Dionex Model
CMMS-II) was utilized.
153.6, 145.5, 144.4, 133.9, 132.9, 127.0, 126.7, 70.9, 69.3, 69.0, 67.8,
60.1, 39.1, 34.0, 31.5, 31.4,14.0. Anal. Calcd for C58H78O10: C, 74.48; H,
8.41. Found: C, 74.07; H, 8.47.
3.1.4. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,27-
3.1.1. 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-
bis(carboxymethoxy)calix[4]arene-1,3-crown-4
bis[(ethoxycarbonyl)methoxy]calix[4]arene-1,3-
(7a) in the 1,3-alternate conformation
crown-4 (12) in the cone conformation
A mixture of diester 14 (2.00 g, 2.14 mmol), 10% Me4NOH
(50 mL) and THF (50 mL) was refluxed for 12 h. The THF was
evaporated in vacuo and the resulting aqueous mixture was cooled
in an ice-bath and acidified with 6 N HCl. The mixture was
extracted with CH2Cl2 (2ꢁ100 mL). The combined organic layers
were washed with water (2ꢁ50 mL) and dried over MgSO4. After
evaporation of the THF in vacuo, di(carboxylic acid) 7a (1.90 g, 99%)
was obtained as a white solid with mp 200–202 ꢂC. IR (deposit from
CDCl3 solution onto a NaCl plate): 3405 (br, O–H), 1767 (C]O),
A mixture of p-tert-butylcalix[4]arene-1,3-crown-4 (11) (5.00 g,
6.55 mmol) and NaH (0.63 g, 26.25 mmol) in 50 mL of THF was
stirred under nitrogen at room temperature for 1 h. Ethyl bro-
moacetate (6.61 g, 21.92 mmol) in THF (10 mL) was added slowly.
The mixture was stirred at room temperature for another 12 h and
quenched with a small amount of water added dropwise. The THF
was evaporated in vacuo and CH2Cl2 (100 mL) and aqueous10% HCl
(50 mL) were added to the residue. The organic layer was separated
and washed with water (2ꢁ50 mL), dried over MgSO4, and evap-
orated in vacuo. Recrystallization of the residue from MeOH gave
4.70 g (80%) of white solid with mp 185 ꢂC. IR (deposit from CDCl3
solution onto a NaCl plate): 1761, 1736 (C]O), 1187, 1126 (C–
1203, 1130 (C–O) cmꢀ1. 1H NMR (CDCl3):
d 7.10 (s, 4H), 7.05 (s, 4H),
4.06 (s, 4H), 3.90 (dd, J¼16.5, 33.0 Hz, 8H), 3.66 (t, J¼4.0 Hz, 4H),
3.48 (t, J¼3.8 Hz, 4H), 2.50 (s, 4H), 1.34 (s, 18H), 1.24 (s, 18H); 13C
NMR:
d 168.1, 154.2, 151.9, 146.8, 146.6, 132.7, 132.6, 126.8, 126.2,
O) cmꢀ1. 1H NMR (CDCl3):
d
7.14 (s, 4H), 6.50 (s, 4H), 4.55 (s, 4H),
71.7, 69.9, 68.4, 68.0, 67.8, 38.6, 34.2, 34.0, 31.6, 31.2. Anal. Calcd for
C54H70O10: C, 73.78; H, 8.03. Found: C, 73.72; H, 8.01.
4.52 (d, J¼12.5 Hz), 4.37 (t, J¼6.0 Hz, 4H), 4.26 (q, J¼7.5 Hz), 4.11 (t,
J¼6.0 Hz, 4H), 3.88 (s, 4H), 3.19 (d, J¼12.5 Hz), 1.34 (s, 18H), 1.31 (t,
J¼7.0 Hz, 6H), 0.81 (s, 18H). 13C NMR:
d
170.1, 154.5, 152.2, 145.1,
3.2. General procedure for preparation of 5,11,17,23-
tetrakis(1,1-dimethylethyl)-25,27-bis[N-(X-sulfonyl)
carbamoylmethoxy]calix[4]arene-1,3-crown-4
compounds 1b–e in the cone conformation
144.5, 135.4, 131.6, 125.6, 124.8, 73.5, 72.2, 70.7, 60.7, 34.1, 33.6, 31.7,
31.1, 30.8, 14.3. Anal. Calcd for C58H78O10: C, 74.48; H, 8.41. Found: C,
74.21; H, 8.40.
3.1.2. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,27-
bis(carboxymethoxy)calix[4]arene-1,3-crown-
4 (1a) in the cone conformation
A solution of dicarboxylic acid 1a (1.33 g, 1.51 mmol) and oxalyl
chloride (1.57 g, 12.4 mmol) in benzene (60 mL) was refluxed for
5 h. The solution was evaporated in vacuo and subjected to high
vacuum for 30 min. The residue was dissolved in THF (20 mL) and
added into a mixture of the appropriate sulfonamide (3.78 mmol)
and NaH (0.36 g, 15.1 mmol) in THF (40 mL) under nitrogen at room
temperature. The reaction mixture was stirred for another 12 h
(except 3 h for p-nitrobenzenesulfonamide). The reaction was
quenched by addition of a small amount of water and the THF was
evaporated in vacuo. The residue was dissolved in CH2Cl2 (100 mL)
and the solution was washed with aqueous 10% K2CO3 solution
(2ꢁ50 mL), 10% HCl (50 mL) and water (2ꢁ50 mL). The organic
layer was dried over MgSO4 and evaporated in vacuo. The residue
was purified by either column chromatography or recrystallization.
A mixture of 12 (2.00 g, 2.14 mmol), 10% Me4NOH (50 mL) and
THF (50 mL) was refluxed for 12 h. The THF was evaporated in
vacuo and the resulting aqueous mixture was cooled in an ice-bath
and acidified with 6 N HCl. The mixture was extracted with CH2Cl2
(2ꢁ100 mL). The combined organic layers were washed with water
(2ꢁ50 mL) and dried over MgSO4. After evaporation of the THF in
vacuo, 1.90 g (99%) of di(carboxylic acid) 1a was obtained as a white
solid with mp 252–254 ꢂC. IR (deposit from CDCl3 solution onto
a NaCl plate): 3369 (br, O–H), 1753 (C]O), 1201, 1129 (C–O) cmꢀ1
1H NMR (CDCl3):
7.16 (s, 4H), 6.48 (s, 4H), 4.38 (s, 4H), 4.29 (d,
J¼12.5 Hz, 4H), 4.20 (s, 4H), 3.94 (s, 4H), 3.20 (d, J¼12.7 Hz, 4H),1.35
(s, 18H), 0.82 (s, 18H); 13C NMR:
171.1, 154.7, 151.0, 145.7, 145.5,
.
d
d
134.9, 131.2, 125.9, 125.1, 73.7, 72.4, 70.5, 69.6, 68.0, 34.1, 33.7, 31.7,
31.0, 30.6. Anal. Calcd for C54H70O10: C, 73.78; H, 8.03. Found: C,
73.86; H, 8.37.
3.2.1. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,27-bis-
[N-(methanesulfonyl) carbamoylmethoxy]calix[4]arene-
1,3-crown-4 (1b) in the cone conformation
The residue was chromatographed on silica gel with EtOAc–
hexanes (1:1) as eluent to produce a white solid in 71% yield with
mp 180–182 ꢂC. IR (deposit from CDCl3 solution onto a NaCl plate):
3.1.3. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,27-
bis[(ethoxycarboxy)methoxy]calix[4]arene-1,3-
crown-4 (14) in the 1,3-alternate conformation
3369 (br, N–H), 1721 (C]O) cmꢀ1 1H NMR (CDCl3):
. d 11.03 (br s,
A mixture of p-tert-butylcalix[4]arene-1,3-crown-4 (11) (5.00 g,
6.6 mmol) and KH (1.05 g, 26.2 mmol) in THF (50 mL) was stirred
under nitrogen at room temperature for 1 h. Ethyl bromoacetate
(6.61 g, 21.9 mmol) in THF (10 mL) was added slowly. The mixture
was stirred at room temperature for another 12 h and the reaction
was quenched by dropwise addition of a small amount of water.
The THF was evaporated in vacuo. CH2Cl2 (100 mL) and aqueous
10% HCl (50 mL) were added to the residue. The organic layer was
separated and washed with water (2ꢁ50 mL), dried over MgSO4,
and evaporated in vacuo. Recrystallization of the residue from
MeOH gave 4.70 g (80%) of white solid with mp 173–176 ꢂC. IR
(deposit from CDCl3 solution onto a NaCl plate): 1762 (C]O), 1179
2H), 7.16 (s, 4H), 6.47 (s, 4H), 4.43 (s, 4H), 4.25 (d, J¼12.5 Hz, 4H),
4.18–4.16 (m, 4H), 4.12–4.08 (m, 4H), 3.97 (s, 4H), 3.39 (s, 6H), 3.23
(d, J¼12.5 Hz, 4H), 1.35 (s, 18H), 0.81 (s, 18H); 13C NMR:
d 169.6,
154.4, 152.1, 145.8, 145.5, 134.8, 130.8, 126.0, 125.3, 75.0, 74.0, 69.8,
67.9, 41.9, 34.2, 33.7, 31.7, 31.0, 30.9. Anal. Calcd for C56H76O12N2S2:
C, 65.09; H, 7.41, N, 2.71. Found: C, 64.80; H, 7.46, N, 2.60.
3.2.2. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,27-bis-
[N-(benzenesulfonyl) carbamoylmethoxy]calix[4]arene-
1,3-crown-4 (1c) in the cone conformation
Rerystallization from MeOH afforded a white solid in 89% yield
with mp 143–146 ꢂC. IR (deposit from CDCl3 solution onto a NaCl
(C–O) cmꢀ1
.
1H NMR (CDCl3):
d
7.10 (s, 4H), 7.05 (s, 4H), 4.14 (d,
plate): 3240 (br, N–H), 1716 (C]O) cmꢀ1. 1H NMR (CDCl3):
d 11.05
J¼16.5 Hz, 4H), 4.00 (m, 4H), 3.85 (d, J¼16.5 Hz, 4H), 3.52 (t,
(br s, 2H), 8.15 (dd, J¼2.7, 13.5 Hz, 4H), 7.70–7.65 (m, 2H), 7.60–7.50
(m, 4H), 7.13 (s, 4H), 6.42 (s, 4H), 4.32 (s, 4H), 4.18 (d, J¼12.5 Hz, 4H),
4.23–4.20 (m, 4H), 4.15–4.11 (m, 4H), 3.99 (s, 4H), 3.10 (d, J¼12.5 Hz,
J¼5.0 Hz, 4H), 3.35 (s, 4H), 3.10 (t, J¼5.0 Hz, 4H), 3.00 (s, 4H), 1.32 (s,
18H), 1.25 (s, 18H), 1.14 (t, J¼7.1 Hz, 6H); 13C NMR:
d 170.3, 154.6,

5898
X. Liu et al. / Tetrahedron 65 (2009) 5893–5898
4H), 1.34 (s, 18H), 0.78 (s, 18H). 13C NMR:
145.4, 138.9, 134.8, 134.0, 130.8, 128.9, 128.5, 125.0, 125.2, 75.1, 73.9,
70.0, 68.3, 34.1, 33.6, 31.7, 31.0. Anal. Calcd for C66H80O12N2S2: C,
68.49; H, 6.97, N, 2.42. Found: C, 68.49; H, 7.20, N, 2.40.
d
168.2, 154.3, 152.2, 145.8,
portion of the organic phase was removed and added to 3.0 mL of
0.10 M HCl in a new 15-mL centrifuge tube. The tube was vortexed
for 10 min and centrifuged for 10 min. A sample of the aqueous
phase from this stripping was diluted 10-fold with DI water and the
alkaline earth metal cation concentrations were determined by ion
chromatography. The pH of the aqueous phase from the initial
extraction step was determined.
3.2.3. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,27-bis[N-(4-
nitrobenzenesulfonyl) carbamoylmethoxy]calix[4]arene-
1,3-crown-4 (1d) in the cone conformation
The residue was chromatographed on silica gel with EtOAc–
hexanes (1:4) as eluent to afford a yellowish solid in 97% yield with
mp 172–174 ꢂC. IR (deposit from CDCl3 solution onto a NaCl plate):
Acknowledgements
3355 (br, N–H), 1726 (C]O) cmꢀ1. 1H NMR (CDCl3):
d 11.4 (br s, 2H),
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.
8.42–8.38 (m, 4H), 8.36–8.40 (m, 4H), 7.14 (s, 4H), 6.44 (s, 4H), 4.34
(s, 4H), 4.23–4.18 (m, 4H), 4.16 (d, J¼12.5 Hz, 4H), 4.19–4.16 (m, 4H),
4.06 (s, 4H), 3.10 (d, J¼12.5 Hz, 4H), 1.34 (s, 18H), 0.79 (s, 18H). 13C
NMR:
d 168.4, 154.3, 152.1, 150.8, 146.1, 145.7, 144.2, 134.6, 130.7,
130.1, 126.0, 125.3, 124.1, 75.0, 74.0, 69.9, 67.9, 67.7, 34.2, 33.6, 31.6,
30.9. Anal. Calcd for C66H78O16N4S2: C, 63.54; H, 6.30, N, 4.49.
Found: C, 63.67; H, 6.58, N, 4.63.
References and notes
1. Asfari, Z.; Wagner, S.; Vicens, J. J. Incl. Phenom. Mol. Recognit. Chem. 1994, 19,
137.
2. Casnati, A.; Ungaro, R.; Asfari, Z.; Vicens, J. In Calixarenes 2001; Asfari, A.,
Bo¨hmer, Harrowfield, J., Vicens, J., Eds.; Kluwer Academic: Dordrecht, The
Netherlands, 2001; pp 356–384.
3. Gutsche, C. D. Calixarenes. An Introduction, 2nd ed.; Royal Society of Chemistry:
Cambridge, UK, 2008, pp 104–107.
4. Silorinne, K.; Nissinen, M. J. Incl. Phenom. Macrocycl. Chem. 2008, 61, 11.
5. Sliwa, W.; Kozlowski, C. Calixarenes and Resorcinarenes. Synthesis, Properties and
Applications; Wiley-VCH: Weinheim, Germany, 2009, pp 165–174.
6. Kim, J. S.; Vicens, J. J. Incl. Phenom. Macrocycl. Chem. 2009, 63, 189.
7. Alfieri, C.; Dradi, E.; Pochini, A.; Ungaro, R.; Andreeti, B. D. J. Chem. Soc., Chem.
Commun. 1983, 1075.
8. Zhou, H.; Surowiec, K.; Purkiss, D. W.; Bartsch, R. A. Org. Biomol. Chem. 2005, 3,
1676.
9. Zhou, H.; Surowiec, K.; Purkiss, D. W.; Bartsch, R. A. Org. Biomol. Chem. 2006, 4,
2983.
10. Tu, C.; Surowiec, K.; Bartsch, R. A. Tetrahedron Lett. 2006, 47, 3443.
11. Zhou, H.; Liu, D.; Gega, J.; Surowiec, K.; Purkiss, D. W.; Bartsch, R. A. Org. Biomol.
Chem. 2007, 5, 324.
3.2.4. 5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,27-bis-
[N-(trifluoromethanesulfonyl) carbamoylmethoxy]calix-
[4]arene-1,3-crown-4 (1b) in the cone conformation
Rerystallization of the residue from EtOAc–hexanes afforded
a white solid in 70% yield, mp 210–212 ꢂC. IR (deposit from CDCl3
solution onto a NaCl plate): 3429 (br, N–H), 1753 (C]O) cmꢀ1. 1H
NMR (CDCl3):
d 7.17 (s, 4H), 6.49 (s, 4H), 4.51 (s, 4H), 4.21 (d,
J¼12.5 Hz, 4H), 4.18–4.15 (m, 4H), 4.08–4.04 (m, 4H), 3.98 (s, 4H),
3.24 (d, J¼12.5 Hz, 4H), 1.35 (s, 18H), 0.81 (s, 18H). 13C NMR:
d 167.7,
154.4, 152.2, 146.1, 145.8, 134.7, 130.8, 126.0, 125.4, 75.2, 73.8, 69.6,
68.0, 66.9, 53.4, 34.2, 33.7, 31.7, 31.0. Anal. Calcd for
C56H70O12N2F6S2: C, 58.93; H, 6.18, N, 2.45. Found: C, 58.95; H, 6.45,
N, 2.34.
12. Zhang, D.; Cao, X.; Purkiss, D. W.; Bartsch, R. A. Org. Biomol. Chem. 2007, 5, 1251.
13. Tu, C.; Surowiec, K.; Bartsch, R. A. Tetrahedron 2007, 63, 4184.
14. Tu, C.; Surowiec, K.; Bartsch, R. A. J. Incl. Phenom. Macrocycl. Chem. 2007, 58, 361.
15. Tu, C.; Surowiec, K.; Gega, J.; Purkiss, D. W.; Bartsch, R. A. Tetrahedron 2008, 64,
1187.
16. Zhang, D.; Crawford, J. D.; Bartsch, R. A. Tetrahedron 2008, 64, 9843.
17. Wang, J.; Zhang, D.; Lawson, T. R.; Bartsch, R. A. Talanta 2009, 78, 477.
18. Ungaro, R.; Pochini, A. J. Incl. Phenom. 1984, 2, 199.
19. Yamamoto, H.; Sakaki, T.; Shinkai, S. Chem. Lett. 1994, 469.
20. Huber, V. J.; Ivy, S. N.; Lu, J.; Bartsch, R. A. Chem. Commun. 1997, 1499.
21. Steed, J. W.; Atwood, J. L. Supramolecular Chemistry, 2nd ed.; Wiley: New York,
NY, 2009, pp 202–203.
3.3. Procedure for competitive solvent extraction of alkaline
earth metal cations
An aqueous solution of four alkaline earth metal chlorides with
Ba(OH)2 or HCl for pH adjustment (2.0 mL, 2.0 mM in each alkaline
earth metal cation species) and 2.0 mL of a 1.0 mM solution of the
ligand in chloroform in a capped, polypropylene, 15-mL centrifuge
tube was vortexed for 10 min at room temperature. The tube was
centrifuged for 10 min to facilitate phase separation. A 1.5-mL