Lower-rim versus upper-rim functionalization in di-ionizable calix[4]arene-crown-5 isomers. Synthesis and divalent metal ion extraction

Article abstract of DOI:10.1016/j.tet.2010.12.006

Two series of di-ionizable calix[4]arene-crown-5 isomers in the cone conformation are synthesized to probe the effect of the pendant acidic group location on their metal ion extraction properties. In one series, the ionizable groups are attached to the lo

Full text of DOI:10.1016/j.tet.2010.12.006

Tetrahedron 67 (2011) 1389e1397
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Lower-rim versus upper-rim functionalization in di-ionizable
calix[4]arene-crown-5 isomers. Synthesis and divalent metal
ion extraction
Yanfei Yang, Gaurav Arora, Fernando A. Fernandez, Jennifer D. Crawford, Kazimierz Surowiec,
*
Eun Kyung Lee, 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 25 October 2010
Received in revised form 1 December 2010
Accepted 2 December 2010
Available online 9 December 2010
Two series of di-ionizable calix[4]arene-crown-5 isomers in the cone conformation are synthesized to
probe the effect of the pendant acidic group location on their metal ion extraction properties. In one
series, the ionizable groups are attached to the lower rim of the calix[4]arene scaffold, which orients
them near the crown ether cavity. In the second series, the ionizable groups are connected to the upper
rim positioning them away from the crown ether ring, but close to the hydrophobic pocket of the
calix[4]arene unit. The metal ion extraction behaviors of the two series of ligands are compared in ex-
Keywords:
Calixarenes
Crown ethers
tractions of alkaline earth metal cations, Hg2þ, and Pb2þ
.
Ó 2010 Elsevier Ltd. All rights reserved.
Proton-ionizable groups
Solvent extraction
1. Introduction
In calixarene-crown ethers, also known as calixcrowns, two
phenolic oxygens of a calixarene scaffold are connected with
a polyether chain.1e6 Most common are calix[4]arene-1,3-crown
ethers in which a calix[4]arene platform is connected with a poly-
ether fragment bridging two distal phenolic oxygens. The first ex-
ample of this type of ligand, p-tert-butylcalix[4]arene-1,3-crown-6
(1) as reported by Ungaro and co-workers7 is shown in Fig. 1
Of particular interest to our metal ion separations research
program has been calix[4]arene-crown ether ligands with two
pendant acidic groups attached to the remaining phenolic oxygens.
Such ligands provide efficient extractions of divalent metal ions
from aqueous solutions into organic diluents. The extraction pro-
ceeds by an ion-exchange mechanism to form electroneutral di-
ionized calixcrown-divalent metal ion complexes in the organic
phase. This avoids the need for concomitant transfer of anions from
the aqueous phase into the organic phase, a very important factor
when highly hydrophilic anions like chloride, nitrate, and sulfate
are involved. The first example of such a di-ionizable calixcrown
compound, p-tert-butylcalix[4]arene-1,3-crown-5 dicarboxylic acid
2 (Fig. 1) was described by Ungaro and co-workers who found that
this ligand exhibited enhanced metal ion extraction ability com-
pared to non-ionizable analogues.8
O
O
O
O
OH
HO
O
O
O
OH
O
HO
O
O
O
O
O
O
O
2
1
Fig. 1. Structures of the first-reported calixcrown 1 and di-ionizable calixcrown 2.
Since 2005, we have been engaged in a systematic structural
variation of di-ionizable calix[4]arene-1,3-crown ether com-
pounds.9e14 Effects of the changes are evaluated in solvent ex-
traction of divalent metal ions from aqueous solutions into
chloroform. The structural variations have included changing: (i)
the size of the crown ether ring from crown-4 to crown-5 to crown-
6;9e11,13 (ii) the conformation of the calix[4]arene scaffold from
cone to partial cone to 1,3-alternate;9e11,13 and (iii) the presence of
substituents on benzene ring positions para to the phenolic oxy-
gens in the calixarene unit.9,11 Also evaluated was the effect of
replacing one oxygen in the polyether fragment with sulfur.12,14 The
* 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 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.12.006

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Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
proton-ionizable groups have included carboxylic acid and N-(X)
sulfonyl carbamoyl, eC(O)NHSO2X, in which the acidity may be
‘tuned’ by varying the inductive effects of X.
with tetraethylene glycol ditosylate and excess Cs2CO3 as the base.
This base was utilized because of the template effect of Csþ in
forming the crown ether unit. Due to elimination of the intra-
molecular hydrogen bonding and the presence of the two small
methoxy groups on the lower rim, compound 7 is conformationally
mobile in the solution. Demethylation of 7 with trimethylsilyl
iodide by adaptation of a reported procedure17 gave 25,27-dihy-
droxycalix[4]arene-crown-5 (8) in 78% yield. Diester 9 was realized
in 50% yield by reaction of 8 with NaH and ethyl bromoacetate in
THF at room temperature. Refluxing diester 9 with tetramethyl-
ammonium hydroxide in aqueous THF overnight followed by
acidification gave diacid 4a in 84% yield. Diacid 4a was transformed
into the corresponding di(acid chloride) by reaction with oxalyl
chloride in refluxing benzene. Commercially available sulfon-
amides were converted into their sodium salts by reaction with
NaH in THF. Subsequently the di(acid chloride) was added and the
reaction was allowed to proceed at room temperature overnight to
give the desired products 4bee in 48e65% yields.
In the cone conformation of calix[4]arene (3), the phenolic oxy-
gen-containing portion is called the lower rim and the aryl group
region is termed the upper rim (Fig. 2).15 To date, our investigations
have involved di-ionizable calix[4]arene-1,3-crown ethers with
pendant acidic groups attached to the lower rim. To provide for
a comparison with ligands in which the ionizable groups have been
moved to the upper rim, we undertook the synthesis and evalua-
tion of two new series of di-ionizable calix[4]arene-1,3-crown-5
compounds 4 and 5 (Fig. 3). The two series are constitutional iso-
mers with the same molecular formula for a given acidic function.
In the former series, the two acidic groups are connected to the
lower rim of the calix[4]arene unit. In the latter, the upper rim bears
the two acidic functions. In Series 4, the two ionizable groups are in
close proximity to the crown ether ring. In Series 5, the acidic
groups are remote from the crown ether ring, but close to the
p
-electron rich cavity of the calixarene unit.
The conformation of ligands 4aee was readily elucidated from
their 1H and 13C NMR spectra using the ‘de Mendoza’ rule.18 A pair
of widely separated AB patterns was observed for the bridge pro-
tons and both of these protons correlated with a carbon signal at
Upper rim
Lower rim
d
31 ppm, confirming that the ligands are in the cone conformation.
3
OH
OH
OH
HO
2.2. Synthesis of cone upper-rim di-ionizable calix[4]arene-
Fig. 2. Upper and lower rims of calix[4]arene in the cone conformation.
crown-5 ligands 5aee
Synthesis of upper-rim functionalized di-ionizable ligands 5aee
is presented in Scheme 2. Following a literature procedure,16 re-
C(O)Y
C(O)Y
Y
a -OH
b
O
O
O
O
O
O
O
O
-NHSO2Me
c
-NHSO2Ph
-NHSO2C6H4-4-NO2
d
O
Y
O
O
Y
O
O
O
e -NHSO2CF3
5a-e
4a-e
O
O
Fig. 3. Isomeric cone calix[4]arene-crown-5 ligands with two pendant acidic groups attached to the lower rim in 4 and to the upper rim in 5.
We now report the synthesis of ligands 4aee and 5aee and
evaluation of their metal ion binding propensities in solvent ex-
traction of divalent metal ions.
action of dimethoxycalix[4]arene 6 with 2 equiv of Br2 in CHCl3
gave dibrominated dimethoxycalix[4]arene 10 in 84% yield.
Reaction of 10 with tetraethylene glycol ditosylate and Cs2CO3 in
refluxing MeCN provided the dibrominated dimethoxycalix[4]-
arene-crown-511 in 58% yield. To a solution of calixcrown 11 in THF
at ꢀ78 ꢁC was added BuLi in hexane followed by bubbling CO2 into
the THF solution of the organolithium intermediate. Following the
reaction, addition of aqueous HCl gave the upper rim-substituted di
(carboxylic acid) 5a as a white precipitate in 78% yield. Di(carbox-
ylic acid) 5a was transformed into the corresponding di(acid
chloride) by reaction with oxalyl chloride in refluxing benzene.
Commercially available sulfonamides were treated with NaH in THF
to convert them into the corresponding sodium salts. Then a THF
solution of the di(acid chloride) in THF was added with reaction at
room temperature for 24 h. Desired products 5bee were isolated in
71e80% yields.
2. Results and discussion
2.1. Synthesis of cone calix[4]arene-crown-5 ligands 4aee
with two lower rim acidic side arms
Preparation of di-ionizable calix[4]arene-crown-5 ethers 4aee
in the cone conformation is depicted in Scheme 1. In adaptation of
a reported method,16 calix[4]arene (3) was reacted with iodo-
methane and K2CO3 in refluxing MeCN to give dimethoxycalix[4]-
arene 6 in 51% yield. For this reaction, it was found that if the
amount of K2CO3 was more than 1 equiv, a mixture of mono-, di-,
and trimethoxycalix[4]arenes resulted and the yield of the desired
dimethylated product decreased. The dimethoxycalix[4]arene
The conformation of ligands 5aee was readily elucidated from
their 1H and 13C NMR spectra. Generally speaking, lower rim al-
kylation by methyl groups results in more flexible calixcrown li-
gands due to elimination of intramolecular hydrogen bonding
between the hydroxyl groups. However, upper-rim substituents
6
remains in the cone conformation due to the hydrogen
bonding between the two remaining hydroxyl groups. The
dimethoxycalix[4]arene-crown-5 7 was realized in 73% yield by
a modified literature procedure17 under high dilution conditions

Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
1391
O
O
O
O
O
O
HO
OH
c
O
O
O
O
a
b
3
OH
O
O
OH
6
O
7
O
8
X
b
c
d
e
-Me
O
O
O
O
O
O
O
O
d
O
O
O
O
O
O
f
O
e
-Ph
-C6H4-4-NO2
-CF3
O
O
O
O
O
O
O
O
O
O
NH
SO2
X
HN
SO2
X
OH
O
HO
O
O
O
9
4a
4b-e
Scheme 1. Synthesis of di-ionizable calix[4]arene-crown-5 ligands 4aee. Reagents and conditions (a) MeI, K2CO3, MeCN, reflux; (b) TsO(CH2CH2O)4Ts, Cs2CO3, MeCN, reflux; (c)
Me3SiI, CHCl3, reflux; (d) BrCH2CO2Et, NaH, THF, rt; (e) TMAOH, aq THF, reflux; (f) (i) (COCl)2, C6H6, reflux; (ii) XSO2NH2, NaH, THF, rt.
Br
Br
Br
Br
b
a
O
O
O
O
O
O
OH
O
O
OH
O
O
OH
OH
6
10
O
11
CO2H
CO2H
C(O)NHSO2X
C(O)NHSO X
2
c
X
d
O
O
O
O
O
O
O
O
O
O
O
O
b
-Me
-Ph
c
d
e
-C6H4-4-NO2
-CF3
O
O
5b-e
5a
Scheme 2. Synthesis of cone, upper-rim functionalized di-ionizable calix[4]arene-crown-5 ligands 5aee. Reagents and conditions: (a) Br2, CHCl3, rt; (b) TsO(CH2CH2O)4Ts, Cs2CO3,
MeCN, reflux; (c) (i) BuLi, THF, ꢀ78 ꢁC; (ii) CO2; (d) (i) (COCl)2, C6H6, reflux; (ii) XSO2NH2, NaH, THF, rt.
restrict rotation of the phenolic units through the calixarene cavity,
especially when acidic groups are present on the upper rim. Cone
conformations were observed for ligands 5aee. A pair of widely
separated AB patterns for the bridge protons was observed and
extractions include hard19 alkaline earth metal cations, in-
termediate Pb2þ, and soft Hg2þ
.
2.3.1. Competitive solvent extraction of alkaline earth metal cations
by cone di-ionizable calix[4]arene-crown-5 ligands 4aee and
5aee. For competitive solvent extraction of aqueous solutions of
alkaline earth metal cations (2.0 mM in each) with 1.0 mM solu-
tions of the di-ionizable calix[4]arene-crown-5 ligands 4aee and
5aee in chloroform, plots of metal ion loading of the organic phase
versus the equilibrium pH of the aqueous phase are presented in
Figs. 4 and 5, respectively.
The extraction selectivity order for ligands 4aee is
Ba2þ>Sr2þ>Ca2þzMg2þ. The total metal cation loading approaches
100%, which is consistent with formation of 1:1 divalent metal ion:
di-ionizedligandextractioncomplexes. TheBa2þ/Sr2þ selectivitiesfor
extractants 4bee increase in the order: eC(O)NHSO2Me<ꢀC(O)
NHSO2Ph<ꢀC(O)NHSO2C6H4e4-NO2<ꢀC(O)NHSO2CF3. This is the
both of these protons correlated with a carbon signal at
d 31 ppm,
confirming that the ligands are in the cone conformation.18
2.3. Effects of position of the two ionizable groups on
divalent metal ion extractions
The effects of changing the positions of the two pendant acidic
groups from the lower rim in 4aee to the upper rim in 5aee were
probed using divalent metal ion extractions from aqueous solutions
into chloroform. As in our previous studies of di-ionizable calix[4]
arene-1,3-crown ether ligands, both competitive solvent extrac-
tions of four alkaline earth metal cations and single species ex-
tractions of Hg2þ and Pb2þ were investigated. The solvent

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Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
a
b
c
d
e
100
80
60
40
20
0
0
2
4
6
8
10 120
2
4
6
8
10 120
2
4
6
8
10 120
2
4
6
8
10 12
0
2
4
6
8
10
pH
Fig. 4. Percent metal loading versus equilibrium pH of the aqueous phase for competitive solvent extraction of alkaline earth metal cations from aqueous solutions into chloroform
by lower-rim di-ionizable calix[4]arene-crown-5 ligands 4aee: (a) 4a, (b) 4b, (c) 4c, (d) 4d, and (e) 4e. (,¼Mg2þ, B¼Ca2þ, 6¼Sr2þ
,
¼Ba2þ).
7
a
b
c
d
e
100
80
60
40
20
0
0
2
4
6
8
10 120
2
4
6
8
10 120
2
4
6
8
10 120
2
4
6
8
10 120
2
4
6
8 10 12
pH
Fig. 5. Percent metal loading versus the equilibrium pH of the aqueous phase for competitive solvent extraction of alkaline earth metal cations into chloroform by upper-rim di-
ionizable calix[4]arene-crown-5 ligands 5aee: (a) 5a, (b) 5b, (c) 5c, (d) 5d, and (e) 5e. (,¼Mg2þ, B¼Ca2þ, 6¼Sr2þ
,
¼Ba2þ).
7
same order in which the electron-withdrawing ability of X and the
acidity of the ionizable group increase. The lowest Ba2þ/Sr2þ selec-
tivity is observed with the di(carboxylic acid) 4a.
Ligands 5bee also exhibit total metal cation loading approach-
ing 100%. So moving the two ionizable groups to the upper rim does
not appreciably alter the alkaline earth metal ion extraction
efficiency. Presumably the somewhat higher metal cation loading
for ligand 5a results from contamination of the organic phase by
finely divided Mg(OH)2 at the highest pHs. Comparison of the re-
sults obtained with 4bee and 5bee reveals that the Ba2þ extraction
selectivity is diminished when the two acid functions are shifted to
the upper rim.

Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
1393
The selectivity exhibited in alkaline earth metal cation extrac-
tion by upper-rim di(carboxylic acid) 5a is strikingly different from
the Ba2þ selectivity shown by ligands 4aee and 5bee. With 5a, the
extraction selectivity order is Mg2þ>Ca2þ>Sr2þ>Ba2þ. Thus, Ba2þ
changed from the best-extracted alkaline earth metal cation with
4aee to 5bee to the worst-extracted species with 5a.
For ligand series 5aee with the two acidic groups on the upper
rim, the alkaline earth metal cation selectivity changes as the type of
ionizable group is varied from carboxylic acid in 5a to N-(X)sulfonyl
carbamoyl in 5bee. As ionized species, the former should be a harder
divalent metal ion coordination site than the latter. The extraction
selectivity observed with 5a correlates with the hardness of the al-
kaline earth metal cations. This suggests that the primary co-
ordination site for association of the alkaline earth metal cations
with di-ionized ligand 5a is with the two carboxylate ion centers on
the upper rim. With the N-(X)sulfonyl carbamoyl groups, in-
teractions of the softer ionized group sites on the upper rim with the
divalent cations are weaker allowing for participation of the crown
for the five different ionizable functions. For the two di(carboxylic
acid) ligands 4a and 5a, a significantly higher extraction level is
observed when the two ionizable groups are attached to the
lower rim. For the acidic functions of eC(O)NHSO2X with X¼Me,
Ph, and C6H4e4-NO2, much higher levels of extraction are found
when the two ionizable groups are attached to the upper rims.
Finally, when the two acidic groups are eC(O)NHSO2CF3, the Hg2þ
loadings are the same for ligands 4e and 5e. Thus the effect of
moving the acidic groups from the lower rim to the upper rim for
extraction of soft Hg2þ is found to depend upon the identity of
the particular ionizable function.
2.3.3. Single species solvent extraction of Pb2þ by cone di-ionizable
calix[4]arene-crown-5 ligands 4aee and 5aee. For single species
extraction of Pb2þ, aqueous solutions containing 1.00 mM Pb2þ
were extracted with 0.50 mM solutions of ligands 4aee and 5aee
in chloroform. Plots of Pb2þ loading of the organic phase versus the
equilibrium pH of the aqueous phase for 4aee (open circles) and for
5aee (filled circles) are presented in Fig. 7. Each panel contains the
data for a Series 4 ligand and a Series 5 ligand with the same ion-
izable group.
ether ring or the p-electron rich cavity of the calix[4]arene unit fa-
voring extraction of the softer alkaline earth metal cation.
2.3.2. Single species solvent extraction of Hg2þ by cone di-ionizable
calix[4]arene-crown-5 ligands 4aee and 5aee. Aqueous solutions
containing 0.25 mM Hg2þ were extracted by 0.25 mM solutions of
ligands 4aee and 5aee in chloroform. Data for Hg2þ loading of the
organic phase versus the equilibrium pH of the aqueous phase in
extractions with 4aee and 5aee are presented as open and filled
circles, respectively, in Fig. 6. Each panel in this figure gives the
extraction profiles for a Series 4 and a Series 5 ligand with the same
ionizable group.
All members of Series 4 produce near quantitative Pb2þ loadings
based on formation of 1:1 Pb2þ-di-ionized ligand extraction
complexes.
Ligands 5aee show two strikingly different extraction behav-
iors toward Pb2þ. High metal loading levels are observed for 5a
and 5e. In sharp contrast, ligands 5bed are very poor Pb2þ
extractants.
When the data for ligands 4 and 5 are considered together, two
patterns are evident. If the acidic groups are eCO2H or eC(O)
NHSO2CF3, both the Series 4 and 5 ligands show strong extraction
propensities toward Pb2þ. On the other hand, when the ionizable
groups are eC(O)NHSO2X with X¼Me, Ph or eC6H4e4-NO2, ex-
traction of Pb2þ is strongly facilitated by location of the two acidic
functions on the lower rims in 4bed.
Ligands 5aee are all moderately good extractants for Hg2þ
with 5c and 5e giving significantly higher metal loading levels
than those for the other three members of the series. In the
comparison of Hg2þ extraction by Series 4 and Series 5 ligands
with the same acidic groups, three different categories are noted
a
b
c
d
e
100
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
0
2
4
6
8
pH
Fig. 6. Percent metal loading versus the equilibrium pH of the aqueous phase for single species solvent extraction of Hg2þ into chloroform by lower-rim di-ionizable calix[4]arene-
crown-5 compounds 4aee and upper-rim di-ionizable calix[4]arene-crown-5 ligands 5aee: (a) 4a and 5a, (b) 4b and 5b, (c) 4c and 5c, (d) 4d and 5d, and (e) 4e and 5e. (B¼4aee,
C¼5aee).

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Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
a
b
c
d
e
100
80
60
40
20
0
0
2
4
6
0
2
4
6
0
2
4
6
0
2
4
6
0
2
4
6
pH
Fig. 7. Percent metal loading versus the equilibrium pH of the aqueous phase for single species solvent extraction of Pb2þ into chloroform by lower-rim di-ionizable calix[4]arene-
crown-5 compounds 4aee and upper-rim di-ionizable calix[4]arene-crown-5 ligands 5aee: (a) 4a and 5a, (b) 4b and 5b, (c) 4c and 5c, (d) 4d and 5d, and (e) 4e and 5e. (B¼4aee,
C¼5aee).
3. Conclusions
For intermediate Pb2þ, all five of the Series 4 extractants exhibit
high metal loadings indicating that positioning of the ionizable
groups near the crown ether unit in the extraction complex is
preferred. Compounds 5bed are found to be very poor extractants
for Pb2þ. In contrast, ligands 5a and 5e give high metal loadings.
Determining the reasons for the extreme variability in Pb2þ ex-
Synthetic routes are established for two series of di-ionizable
calix[4]arene-crown-5 isomers in cone conformations. In Series 4
ligands, the two acidic side arms are attached to the lower rim of
the calix[4]arene unit. In Series 5 compounds, the two ionizable
groups are connected to the upper rim of the calix[4]arene scaffold.
In both series, ligands with five different acidic functions are
employed including eCO2H and eC(O)NHSO2X with variation in
the inductive effects of X.
To probe the effect of locating the two ionizable groups on the
lower-rim versus the upper rim, solvent extraction of divalent
cations from aqueous solutions into chloroform are employed. This
includes extractions of hard alkaline earth metal cations, in-
termediate Pb2þ, and soft Hg2þ.
tractions within the Series
investigation.
5 ligands will require further
4. Experimental
4.1. General
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 1H and 13C NMR spectra were recorded with a Varian
Unity INOVA 500 MHz FT-NMR (1H 500 MHz and 13C 126 MHz)
spectrometer in CDCl3 with Me4Si as an internal standard. Chemical
From comparison of the extraction results for the Series 4 and 5
isomers, insight into the effect of locating the two acidic groups on
the lower-rim versus the upper rim is gained. The effect is found to
differ depending upon the metal ion species being extracted and
the identity of the ionizable groups.
shifts (d) are given in parts per million downfield from TMS and
Ligands in Series 4 and 5 are efficient alkaline earth metal cation
extractants and nearly all exhibit selectivity for Ba2þ, which would
fit within the crown ether cavity. The exception is ligand 5e with
extraction selectivity for Mg2þ suggesting coordination with the
oxygens of the two carboxylate groups on the upper rim of the di-
ionized ligand.
coupling constants values (J) are in hertz. Elemental analysis was
performed by Desert Analytics Laboratory (now Columbia Analyt-
ical Services) of Tucson, Arizona. For compounds 5a, 5c, and 11, the
combustion analysis results indicated the presence of small
amounts of CH2Cl2 in the samples. This was verified by singlets at
d
5.32 in their 1H NMR spectra.
When the results are taken together, the Series 5 ligands are
Reagents were purchased from commercial suppliers and used
better Hg2þ extractants (45e80% loading) than the compounds in
directly unless stated otherwise. Acetonitrile (MeCN) was dried
over CaH2 and distilled immediately before use. Tetrahydrofuran
(THF) was dried over sodium with benzophenone as an indicator
Series 4. This suggests coordination of soft Hg2þ in the
p-electron
rich cavity of the calix[4]arene unit near the ionized groups on the
upper rim. Ligands of Series 4 exhibit large differences in their
abilities to extract Hg2þ. Compounds 4bed are found to be very
poor Hg2þ extractants. On the other hand, ligands 4a and 4e give
high metal loadings (near 80%). Reasons for the high variability in
Hg2þ extractions within the Series 4 ligands are not evident at this
time.
ꢀ
and distilled just before use. DMF was dried over activated 4 A
molecular sieves for 24 h before use. Synthesis of the ditosylate of
tetraethylene glycol was performed by a conventional aqueous THF
method.20
For use in the metal ion extractions, reagent-grade chloroform
was washed with an equal volume of deionized water to remove

Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
1395
the stabilizing ethanol and stored in the dark. Vortexing and cen-
trifugation 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
extraction experiment was measured with a Fisher Accumet AR25
pH meter with a Corning 476,157 combination pH electrode.
solvent of CH2Cl2 (5 mL) and MeOH (50 mL). For compound 9, 1.66 g
(50%) was realized as a pale yellow solid with mp 201e204 ꢁC. IR
(deposit on a NaCl plate from CH2Cl2 solution): 1758 (C]O) cmꢀ1
.
1H NMR (500 MHz, CDCl3):
d
1.26 (t, J¼7.0 Hz, 6H), 3.23 and 4.60 (AB
q, J¼13.0 Hz, 8H), 3.71e3.79 (m, 8H), 4.04 (t, J¼6.5 Hz, 4H), 4.18 (q,
J¼7.0 Hz, 4H), 4.30 (t, J¼6.5 Hz, 4H), 4.87 (s, 4H), 6.51 (s, 6H), 6.73 (t,
J¼7.5 Hz, 2H), 6.89 (d, J¼7.5 Hz, 4H). 13C NMR (126 MHz, CDCl3):
4.2. Synthesis of cone, lower rim, di-carboxyl calix[4]arene-
crown-5 ligand 4a
d 14.2, 31.4, 60.5, 69.6, 70.3, 70.9, 71.1, 72.8, 122.4, 127.9, 128.7, 134.4,
135.3, 154.6, 152.0, 170.0. Anal. Calcd for C44H50O11: C, 70.01; H,
6.68. Found: C, 69.86; H, 6.93.
4.2.1. 25,27-Dimethoxycalix[4]arene (6). To
a
suspension of
calix[4]arene (3) (8.30 g, 19.56 mmol) and anhydrous K2CO3 (3.57 g,
25.87 mmol) in MeCN (160 mL) under nitrogen was added CH3I
(2.43 mL, 41.10 mmol) and the mixture was refluxed for 24 h. After
evaporation of the solvent in vacuo, the residue was taken up in
CH2Cl2 (200 mL) and the solution was washed with 1 N HCl
(2ꢂ80 mL) and brine (2ꢂ50 mL). The organic layer was dried over
MgSO4. After recrystallization from EtOHeCH2Cl2, 4.50 g (51%) of 6
was obtained as a white solid with mp 305e307 ꢁC (lit.16 mp
>300 ꢁC). IR (deposit on a NaCl plate from CH2Cl2 solution): 3100
4.2.5. Cone 25,27-di(carboxymethoxy)calix[4]arene-crown-5 (4a). To
a solution of diester 9 (2.40 g, 3.18 mmol) in THF (40 mL) was added
10% aqueous tetramethylammonium hydroxide (40 mL) and the
solution was refluxed for 24 h. The THF was evaporated in vacuo and
the residue was acidified with 6 N HCl (25 mL). CH2Cl2 (50 mL) was
added and the organic layer was separated. The aqueous layer was
extracted with CH2Cl2 (2ꢂ25 mL). The combined organic layers were
dried over MgSO4 and the solvent was evaporated in vacuo to give
1.87 g (84%) of 4a as a white solid with mp 270e274 ꢁC. IR (deposit on
a NaCl plate from CH2Cl2 solution): 2800e3300 (eCO2H), 1746 (C]
(OH) cmꢀ1 1H NMR (500 MHz, CDCl3):
. d 3.40 and 4.30 (AB q,
J¼13.3 Hz, 8H), 3.98 (s, 6H), 6.65e6.73 (m, 4H), 6.86 (d, J¼7.6 Hz,
O) cmꢀ1. 1H NMR (500 MHz, CDCl3):
d
3.33 and 4.42 (AB q, J¼13.0 Hz,
4H), 7.07 (d, J¼7.4, 4H), 7.75 (s, 2H).
8H), 3.87 (s, 8H), 3.93e3.99 (m, 4H), 4.04e4.12 (m, 4H), 5.33 (s, 4H),
6.51 (t, J¼8.0 Hz, 2H), 6.63 (d, J¼7.5 Hz, 4H), 6.93 (t, J¼7.5 Hz, 2H), 7.13
4.2.2. 25,27-Dimethoxycalix[4]arene-crown-5 (7). To a solution of 6
(4.52 g, 10.00 mmol) in MeCN (1500 mL) under nitrogen, Cs2CO3
(13.03 g, 40.00 mmol) and the ditosylate of tetraethylene glycol
(5.52 g, 11.00 mmol) were added and the mixture was refluxed for
24 h. The MeCN was removed in vacuo. To the residue, CH2Cl2
(350 mL) and 10% aqueous HCl (350 mL) were added. The organic
layer was separated, washed with water (2ꢂ100 mL), and dried
over MgSO4. The solvent was evaporated in vacuo and the crude
product was recrystallized from CH2Cl2 (20 mL) and MeOH
(120 mL) to give 4.46 g (73%) of 7 as a white solid with mp
216e218 ꢁC (lit.17 mp 220e221 ꢁC). 1H NMR (500 MHz, CDCl3):
(d, J¼7.5 Hz, 4H), 10.80 (br s, 2H). 13C NMR (126 MHz, CDCl3):
d 32.3,
70.2, 70.8, 74.0, 124.2, 129.3, 129.4, 133.6, 136.0, 154.2, 155.8, 172.3.
Anal. Calcd for C40H42O11: C, 68.76; H, 6.06. Found C, 68.40; H, 6.33.
4.3. General procedure for synthesis of cone 25,27-di[N-(X)
sulfonyl carboxamidomethoxy]calix[4]arene-crown-5
compounds 4bee
Di(carboxylic acid) 4a (1.20 g, 1.72 mmol) was dried using
a benzene azeotrope. To the resulting solution under nitrogen, oxalyl
chloride (1.20 mL, 13.70 mmol) was added and the solution was
refluxed for 20 h. Progress of the conversion was monitored by IR
spectroscopy. The C]O peak absorbs at 1740 cmꢀ1 for 4a and at
1810 cmꢀ1 for the corresponding di(acid chloride). The solvent and
excess oxalyl chloride were evaporated in vacuo and the residue was
subjected to oil pump vacuum for 20 min. The di(acid chloride) was
used directly in the following reaction without further purification.
The commercial sulfonamide (3.50 mmol) was reacted with NaH
(0.84 g, 35.00 mmol) in freshly distilled THF (50 mL) under nitrogen.
The crude di(acid chloride) was dissolved in freshly distilled THF
(25 mL) and the solution was added into the flask with the sulfon-
amide sodium salt and the mixture was stirred at room temperature
for 24 h. The THF was evaporated in vacuo and the residue was
dissolved in CH2Cl2 (100 mL). The solution was washed with 1 N HCl
(2ꢂ100 mL) and then water (2ꢂ100 mL) and dried over MgSO4. The
solvent was evaporated in vacuo and the residue was recrystallized
from a mixed solvent of CH2Cl2 (10 mL) and MeOH (50 mL).
d
3.19 and 4.41 (AB q, J¼13.0 Hz, 8H), 3.56 (t, J¼3.0 Hz, 4H), 3.74 (t,
J¼3.0 Hz, 4H), 3.92 (d, J¼4.5 Hz, 4H), 3.98 (d, J¼4.5 Hz, 4H), 4.12 (s,
6H), 6.41 (t, J¼7.5 Hz, 2H), 6.52 (d, J¼7.5 Hz, 4H), 6.90 (t, J¼7.5 Hz,
2H), 7.12 (d, J¼7.5 Hz, 4H).
4.2.3. 25,27-Dihydroxycalix[4]arene-crown-5 (8). To a solution of 7
(1.96 g, 2.99 mmol) in CHCl3 (120 mL) under nitrogen was added
Me3SiI (0.84 mL, 6.27 mmol) and the solution was refluxed for 4 h.
The color of the solution changed from yellow to pink after
10e15 min of refluxing. After cooling to room temperature, the
reaction was quenched with 10% aqueous HCl. The organic layer
was separated, washed with satd aq Na2S2O3 and water (2ꢂ50 mL),
dried over MgSO4, and evaporated in vacuo. The residue was
recrystallized from CH2Cl2 (15 mL) and MeOH (75 mL) to give 1.46 g
(78%) of 8 as a white solid with mp 271e274 ꢁC (lit.21 mp
275e276 ꢁC). IR (deposit on a NaCl plate from CH2Cl2 solution):
3374 (OH) cmꢀ1. 1H NMR (500 MHz, CDCl3):
d 3.36 and 4.42 (AB q,
J¼13.0 Hz, 8H), 3.86 (t, J¼5.5 Hz, 4H), 3.96 (t, J¼5.5 Hz, 4H),
4.06e4.14 (m, 8H), 6.67 (t, J¼7.5 Hz, 2H), 6.71 (t, 2H, J¼7.5 Hz), 6.86
(d, J¼7.5 Hz, 4H), 7.07 (d, J¼7.5 Hz, 4H), 7.74 (s, 2H).
4.3.1. Cone 25,27-di[N-(methanesulfonyl) carbamoylmethoxy]calix
[4]arene-crown-5 (4b). The compound was obtained in 48% yield as
a white solid with mp 288e290 ꢁC. IR (deposit on a NaCl plate from
CH2Cl2 solution): 1716 (C]O) cmꢀ1 1H NMR (500 MHz, CDCl3):
.
4.2.4. Cone 25,27-di[(ethoxycarbonyl)methoxy]calix[4]arene-crown-
5 (9). To a solution of 8 (2.61 g, 4.48 mmol) in THF (54 mL) and DMF
(6 mL) under nitrogen was added NaH (1.08 g, 44.80 mmol). The
mixture was stirred at room temperature for 30 min before addi-
tion of BrCH2CO2Et (4.00 mL, 35.50 mmol). The mixture was stirred
for 24 h at room temperature and then the reaction was quenched
by addition of 1 N HCl (10 mL). After the solvent was evaporated in
vacuo, the residue was dissolved in CH2Cl2 (80 mL). The solution
was washed with water (2ꢂ40 mL), dried over MgSO4, and evap-
orated in vacuo. The residue was recrystallized from a mixed
d
3.24 (s, 6H), 3.31 and 4.40 (AB q, J¼13.0 Hz, 8H), 3.87e3.88 (m,
4H), 3.95e3.97 (m, 4H), 4.00e4.02 (m, 4H), 4.10e4.12 (m, 4H), 5.31
(s, 4H), 6.46 (t, J¼7.5 Hz, 2H), 6.54 (d, J¼7.5 Hz, 4H), 6.97 (t, J¼7.5 Hz,
2H), 7.15 (d, J¼7.5 Hz, 4H), 10.73 (s, 2H). 13C NMR (126 MHz, CDCl3):
d
32.4, 42.1, 70.9, 71.4, 72.6, 123.9, 124.3, 128.8, 129.3, 133.3, 136.4,
154.5, 154.6, 170.0. Anal. Calcd for C42H48N2O13S2: C, 59.14; H, 5.67;
N, 3.28. Found: C, 59.34; H, 5.77; N, 3.30.
4.3.2. Cone 25,27-di[N-(benzenesulfonyl) carbamoylmethoxy]calix[4]
arene-crown-5 (4c). The compound was produced in 51% yield as

1396
Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
a white solid with mp 277e279 ꢁC. IR (deposit on a NaCl plate from
CH2Cl2 solution): 1720 (C]O) cmꢀ1 1H NMR (500 MHz, CDCl3):
Calcd for C38H40O7Br2ꢃ0.2CH2Cl2: C, 58.41; H, 5.18. Found: C, 58.60;
.
H, 5.14.
d
2.98 and 4.11 (AB q, J¼13.0 Hz, 8H), 3.85e3.92 (m,12H), 3.98e4.00
(m, 4H), 5.13 (s, 4H), 6.36 (dd, J¼6.5 Hz, 2H), 6.42 (d, J¼7.0 Hz, 4H),
6.85 (dd, J¼7.5 Hz, 2H), 6.95 (d, J¼7.5 Hz, 4H), 7.51 (t, J¼8.0 Hz, 4H),
7.63e7.66 (m, 2H), 8.06 (d, J¼8.0 Hz, 4H), 10.82 (s, 2H). 13C NMR
4.4.3. 25,27-Dimethoxy-11,23-di(carboxy)calix[4]arene-crown-5
(5a). A solution of 11 (1.00 g, 1.32 mmol) in freshly distilled THF
(50 mL) under nitrogen was cooled in a dry iceeacetone bath for
30 min before the addition of 1.6 M n-BuLiehexanes solution
(4.62 mmol). The mixture was stirred for 15 min at that tempera-
ture before CO2 was bubbled through the solution for 30 min. After
another 30 min at ꢀ78 ꢁC, the mixture was allowed to warm to
room temperature. After evaporating the THF in vacuo, 1 N HCl was
added to the residue. The precipitate was filtered and the filter cake
was washed with water (25 mL) and then CH2Cl2 (25 mL) to give 5a
(0.72 g, 78%) as a white solid with mp 372e374 ꢁC. IR (deposit on
a NaCl plate from CH2Cl2 solution): 3305 (OH),1751 (C]O) cmꢀ1. 1H
(126 MHz, CDCl3):
d 32.2, 70.7, 71.0, 71.0, 71.4, 72.5, 123.7, 124.0,
128.7, 128.8, 129.0, 129.3, 133.3, 134.3, 136.4, 139.5, 154.2, 154.6,
168.1. Anal. Calcd for C52H52N2O13S2: C, 63.92; H, 5.36; N, 2.87.
Found: C, 63.76; H, 5.55; N, 2.75.
4.3.3. Cone 25,27-di[N-(4-nitrobenzenesulfonyl) carbamoylmethoxy]
calix[4]arene-crown-5 (4d). The compound was realized in 65%
yield as a pale yellow solid with mp 291e293 ꢁC. IR (deposit on
a NaCl plate from CH2Cl2 solution): 1718 (C]O) cmꢀ1 1H NMR
.
(500 MHz, CDCl3):
d
3.02 and 4.12 (AB q, J¼13.0 Hz, 8H), 3.88e3.90
NMR (500 MHz, CDCl3):
d
3.25 (d, J¼20.5 Hz, 4H), 3.58 (m, 4H), 3.69
(m, 4H), 3.95e4.10 (m, 12H), 5.19 (s, 4H), 6.35e6.42 (m, 6H), 6.84
(dd, J¼7.0 Hz, 2H), 6.93 (d, J¼7.5 Hz, 4H), 8.22 (d, J¼9.0 Hz, 4H), 8.32
(m, 4H), 3.88 (m, 8H), 4.15 (s, 6H), 4.35 (d, J¼20.5 Hz, 4H), 6.40e6.95
(m, 3H), 7.20e7.62 (m, 7H), 12.15 (br s, 2H). 13C NMR (126 MHz,
(d, J¼9.0 Hz, 4H), 10.95 (s, 2H). 13C NMR (126 MHz, CDCl3):
d
32.3,
CDCl3): d 30.5, 39.0, 39.7, 40.0, 67.0, 70.6, 73.8, 123.0, 128.8, 129.5,
70.7, 71.0, 71.4, 72.5, 124.0, 124.3, 124.4, 128.8, 129.2, 130.3, 133.0,
136.2, 144.6, 151.2, 154.1, 154.4, 168.3. Anal. Calcd for
C52H50N4O17S2: C, 58.53; H, 4.72; N, 5.25. Found: C, 58.68; H, 4.97;
N, 5.10.
133.7,135.6,158.7,159.7,166.8. Anal. Calcd for C40H42O11ꢃ0.2CH2Cl2:
C, 67.46; H, 5.97. Found: C, 67.72; H, 5.49.
4.5. General procedure for preparation of the 25,27-
dimethoxy-11,23-di[N-(X-sulfonyl) carbamoyl]calix[4]arene-
crown-5 compounds 5bee
4.3.4. Cone 25,27-di[N-(trifluoromethanesulfonyl) carbamoylmeth-
oxy]calix[4]arene-crown-5 (4e). The compound was obtained in
53% yield as a white solid with mp 227e229 ꢁC. IR (deposit on
Diacid 5a (1.00 g, 1.49 mmol) was dried with a benzene azeo-
trope before addition of oxalyl chloride (1.89 g, 14.90 mmol) in
benzene (50 mL). The solution was refluxed overnight. Diacid 5a
has poor solubility in benzene, while a clear solution was obtained
upon formation of di(acid chloride). After conversion to the di(acid
chloride) was confirmed by an IR shift of the C]O functional group
absorption from 1695 cmꢀ1 in 5a to 1752 cmꢀ1 for the di(acid
chloride), the benzene was evaporated in vacuo and the residue
was subjected to oil pump vacuum for 30 min. The residue was
dissolved in freshly distilled THF (20 mL) and the solution was
added to a mixture of the appropriate sulfonamide (3.28 mmol) and
NaH (0.35 g, 14.90 mmol) in THF (25 mL) under nitrogen at room
temperature. The reaction mixture was refluxed for 2 days. The THF
was removed in vacuo and CH2Cl2 (50 mL) and 10% HCl solution
(50 mL) were added to the residue. The organic layer was separated,
washed with water (2ꢂ50 mL), and dried over MgSO4. Evaporation
of the CH2Cl2 in vacuo gave the crude product, which was purified
by column chromatography on silica gel.
a NaCl plate from CH2Cl2 solution): 1751 (C]O) cmꢀ1 1H NMR
.
(500 MHz, CDCl3):
d
3.32 and 4.30 (AB q, J¼13.0 Hz, 8H), 3.86e3.89
(m, 4H), 3.91e3.94 (m, 4H), 4.00e4.03 (m, 4H), 4.10e4.12 (m, 4H),
5.34 (s, 4H), 6.46 (t, J¼7.5 Hz, 2H), 6.53 (d, J¼7.5 Hz, 4H), 6.97 (t,
J¼7.5 Hz, 2H), 7.14 (d, J¼7.5 Hz, 4H),11.14 (s, 2H). 13C NMR (126 MHz,
CDCl3):
d 32.4, 70.7, 70.8, 70.8, 71.8, 72.3, 124.1, 124.7, 128.9, 129.4,
133.1, 136.2, 153.8, 154.5, 167.3. Anal. Calcd for C42H42F6N2O13S2: C,
52.50; H, 4.41; N, 2.92. Found: C, 52.28; H, 4.62; N, 2.67.
4.4. Synthesis of cone, upper rim, di-carboxy calix[4]arene-
crown-5 ligand 5a
4.4.1. 11,23-Dibromo-25,27-dimethoxy-26,28-dihydroxycalix[4]arene
(10).16 To a stirred solution of 6 (5.00 g, 11.05 mmol) in CHCl3
(225 mL) at 0 ꢁC was added dropwise a solution of Br2 (3.55 g,
22.10 mmol) in CHCl3 (225 mL) during a 2-h period. Afterward the
reaction mixture was kept at room temperature for 2 h. The pre-
cipitate was filtered and the solid was washed with cold CHCl3
(20 mL). The filter cake was stirred in CH2Cl2 (50 mL) at room
temperature for 2 h and filtered. The solid was dried in vacuo to
give 10 as a white solid with mp 362 ꢁC (lit.16 mp >300 ꢁC) in 84%
yield.
4.5.1. Cone 25,27-dimethoxy-11,23-di[N-(methanesulfonyl) carbam-
oyl]calix[4]arene-crown-5 (5b). After chromatography with
CH2Cl2eMeOH (250:1 to 10:1) as eluent, 5b was isolated in 75%
yield as a white solid with mp 212e218 ꢁC. IR (deposit on a NaCl
plate from CH2Cl2 solution): 3249 (NH), 1680 (C]O) cmꢀ1. 1H NMR
4.4.2. 11,23-Dibromo-25,27-dimethoxycalix[4]arene-crown-5 (11). A
mixture of 10 (5.00 g, 8.22 mmol) and Cs2CO3 (6.69 g, 20.55 mmol)
in MeCN (600 mL) under nitrogen was stirred at reflux for 30 min
and then a solution of the ditosylate of tetraethylene glycol (4.56 g,
9.04 mmol) in MeCN (50 mL) was added during a 1-h period. The
mixture was refluxed for 66 h and allowed to cool to room tem-
perature. After evaporation of the solvent in vacuo, the residue was
taken up in CH2Cl2 (250 mL) and the resulting solution was washed
with 2 N HCl (100 mL) and water (2ꢂ250 mL). The organic layer was
dried over MgSO4 and evaporated in vacuo. Recrystallization of the
residue from CH2Cl2eMeOH gave 11 in 58% yield as a white solid
(500 MHz, CDCl3):
4H), 3.77 (m, 4H), 3.95 (m, 8H), 4.15 (s, 6H), 4.55 (d, J¼12.0 Hz, 4H),
6.63e7.50 (m, 10H), 9.01 (s, 2H). 13C NMR (126 MHz, CDCl3):
31.1,
61.1, 70.6, 71.3, 73.8, 76.7, 77.0, 77.2, 123.8, 128.5, 129.1, 134.6, 135.3,
160.4, 166.6. Anal. Calcd for C42H48O13N2S2: C, 59.14; H, 5.67; N,
3.28. Found: C, 59.35; H, 5.64; N, 3.01.
d
2.95 (s, 6H), 3.29 (d, J¼12.0 Hz, 4H), 3.63 (m,
d
4.5.2. Cone 25,27-dimethoxy-11,23-di[N-(benzenesulfonyl) carbamoyl]
calix[4]arene-crown-5 (5c). Chromatography with CH2Cl2eMeOH
(250:1 to 10:1) as eluent produced 5c in 79% yield as a white solid
with mp 288e290 ꢁC. IR (deposit on a NaCl plate from CH2Cl2
solution): 3175 (NH), 1680 (C]O) cmꢀ1. 1H NMR (500 MHz, CDCl3):
with mp 260e264 ꢁC. 1H NMR (500 MHz, CDCl3):
d 3.14 (d,
J¼12.5 Hz, 4H), 3.52 (m, 4H), 3.72 (m, 4H), 3.90 (m, 8H), 4.09 (s, 6H),
d
3.20 (d, J¼12.4 Hz, 4H), 3.55 (m, 4H), 3.75 (m, 4H), 3.90 (m, 8H), 4.15
(s, 6H), 4.44 (d, J¼12.3 Hz, 4H), 6.97 (m, 7H), 7.25 (m, 6H), 7.55 (m,
7H), 8.05 (m, 4H), 9.82 (m, 2H). 13C NMR (126 MHz, CDCl3):
22.5,
31.2, 36.8, 43.6, 60.4, 65.9, 76.7, 77.0, 77.2, 128.3, 128.6, 128.7, 129.6,
4.45 (d, J¼12.5 Hz, 4H), 6.65 (s, 4H), 6.95 (t, J¼7.5 Hz, 2H), 7.12 (d,
J¼7.5 Hz, 4H). 13C NMR (126 MHz, CDCl3):
d
31.0, 70.8, 70.8, 71.5,
d
73.2, 76.5, 77.0, 77.2, 123.1, 128.7, 130.6, 135.8, 154.6, 159.1. Anal.

Y. Yang et al. / Tetrahedron 67 (2011) 1389e1397
1397
129.8, 130.0, 131.4, 133.5, 133.8, 134.0, 134.2, 138.6, 138.8, 156.7, 157.5,
170.6. Anal. Calcd for C52H52O13N2S2ꢃ0.1CH2Cl2: C, 63.49; H, 5.34; N,
2.84. Found: C, 63.30; H, 5.53; N, 3.08.
1A Mercury Vaporizor Unit. The Hg2þ in the sample was reduced
using 5 mL of a 0.5 M solution of SnCl2. The reduced mercury vapor
was then pumped through a flow cell and the mercury concen-
tration was measured at 253.6 nm with a Shimadzu AA-6300
Spectrophotometer.
4.5.3. Cone 25,27-dimethoxy-11,23-di[N-(4-nitrobenzenesulfonyl) car-
bamoyl]calix[4]arene-crown-5 (5d). Chromatography with CH2
Cl2eMeOH (250:1 to 10:1) as eluent gave 5d in 71% yield as a yellow
solid with mp 268e270 ꢁC. IR (deposit from CH2Cl2 solution on
4.6.3. Single species extraction of Pb2þ into chloroform. A 1.00 mM
aqueous solution of Pb(NO3)2 with tetramethylammonium hy-
droxide (TMAOH) or HNO3 for pH adjustment (2.00 mL) and
a 0.50 mM ligand solution in chloroform (2.00 mL) in a capped,
polypropylene, 15-mL centrifuge tube was vortexed for 10 min. The
tube was then centrifuged for 10 min to facilitate phase separation.
A 1.50-mL portion of the organic phase was removed and placed in
a new, 15-mL polypropylene centrifuge tube with 3.00 mL of 4.0 M
HNO3. The tube was vortexed for 10 min and then centrifuged for
10 min. The Pb2þ concentration of the aqueous phase from strip-
ping was determined using a Shimadzu AA-6300 Spectrophoto-
meter. The pH of the aqueous phase in the initial extraction was
measured.
.
a NaCl plate): 3414 (NH), 1685 (C]O) cmꢀ1 1H NMR (500 MHz,
CDCl3):
d
3.29 (d, J¼13.0 Hz, 4H), 3.51e3.87 (m, 16H), 4.08 (s, 6H),
4.32 (d, J¼13.0 Hz, 4H), 6.88 (t, J¼7.5 Hz, 2H), 7.22 (d, J¼7.5 Hz, 4H),
7.31 (s, 4H), 8.12 (d, J¼9.0 Hz, 4H), 8.36 (d, J¼9.0 Hz, 4H), 12.48 (br s,
2H). 13C NMR (126 MHz, CDCl3):
d 30.6, 60.8, 69.9, 70.0, 70.5, 74.2,
123.2, 124.2, 128.9, 129.2, 129.2, 134.1, 134.9, 145.0, 150.0, 158.5, 160.6,
165.0. Anal. Calcd for C52H50N4O17S2: C, 58.53, H, 4.72; N, 5.25.
Found: C, 58.15; H, 4.89; N, 5.12.
4.5.4. Cone 25,27-dimethoxy-11,23-di[N-(trifluoromethanesulfonyl)
carbamoyl]calix[4]arene-crown-5 (5e). Chromatography with CH2
Cl2eMeOH (250:1 to 10:1) as eluent produced 5e in 80% yield as
a pale yellow solid with mp 192 ꢁC. IR (deposit from CH2Cl2 solution
on a NaCl plate): 3620 (NH), 1729 (C]O) cmꢀ1. 1H NMR (500 MHz,
Acknowledgements
CDCl3):
d
3.27 (d, J¼13.0 Hz, 4H), 3.55 (t, J¼3.0 Hz, 4H), 3.74 (t,
We thank the Division of Chemical Sciences, Geosciences, and
Biosciences of the U.S. Department of Energy (Grant DE-FG02-
90ER1446) for support of this research.
J¼3.0 Hz, 4H), 3.92e4.01 (m, 8H), 4.44 (d, J¼13.0 Hz, 4H), 6.95 (s,
4H), 7.00 (t, J¼7.0 Hz, 2H), 7.23 (d, J¼7.0 Hz, 4H), 9.77 (br s, 2H). 13C
NMR (126 MHz, CDCl3):
d 31.1, 70.5, 70.8, 71.6, 73.4, 117.8, 120.4,
123.5, 125.7, 128.6, 129.1, 135.0, 136.0, 159.1, 160.6, 164.2. Anal. Calcd
for C42H42F6N2O13S2: C, 52.50, H, 4.41; N, 2.92. Found: C, 52.80; H,
4.75; N, 3.16.
References and notes
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4.6. Solvent extraction procedures
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€
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4.6.1. Competitive extraction of alkaline earth metal cations into
chloroform. An aqueous solution of the alkaline earth metal chlo-
rides with Ba(OH)2 or HCl for pH adjustment (2.00 mL, 2.0 mM in
each of the four alkaline earth metal cation species) and 2.00 mL of
a 1.0 mM ligand solution in chloroform were placed in a capped,
polypropylene, 15-mL centrifuge tube and vortexed for 10 min. The
tube was centrifuged for 10 min for phase separation. A 1.50-mL
portion of the organic phase was removed and added to 3.00 mL of
0.10 M HCl in a new capped, polypropylene, 15-mL centrifuge tube.
The tube was vortexed for 10 min and centrifuged for 10 min. A
1.00 mL portion of the aqueous phase from stripping was removed
and diluted to 10.0 mL with deionized water. The alkaline earth
metal cation concentrations were determined with a Dionex DX-
120 Ion Chromatograph with a CS12A column. The pH of the
aqueous phase from the initial extraction step was measured.
Netherlands, 2001; pp 356e384.
3. Gutsche, C. D. Calixarenes. An Introduction, 2nd ed.; Royal Society of Chemistry:
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Applications; Wiley-VCH: Weinheim, Germany, 2009, pp 165e174.
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4.6.2. Single species extraction of Hg2þ into chloroform. An aqueous
solution of 0.25 mM Hg(NO3)2 with HNO3 or TMAOH for pH ad-
justment (3.00 mL) and 3.00 mL of a 0.25 mM ligand solution in
chloroform were placed in a capped, polypropylene, 15-mL centri-
fuge tube. The tube was vortexed for 10 min and then centrifuged
for 10 min to allow for phase separation. A 0.50-mL sample of the
aqueous phase was removed and diluted to 5.00 mL with deionized
water. The pH of the aqueous phase was measured. A 1.00-mL
portion of the diluted sample was added to 100 mL of 1.0 N H2SO4 in
a glass reaction bottle, which was then placed on a Shimadzu MVU-
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