Calix[4]arene-dithiacrown ethers: synthesis and potentiometric membrane sensing of Hg2+

Article abstract of DOI:10.1016/j.tet.2009.11.058

A series of calix[4]arene-dithiacrown-5 and -dithiacrown-6 compounds in cone and 1,3-alternate conformations has been synthesized. Responses of these ionophores to Hg²⁺ and competing metal ions were determined in solvent polymeric membrane electrodes. High potentiometric selectivity for Hg²⁺ over Na⁺ and a variety of transition and heavy metal ions was obtained.

Full text of DOI:10.1016/j.tet.2009.11.058

Tetrahedron 66 (2010) 447–454
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Calix[4]arene-dithiacrown ethers: synthesis and potentiometric membrane
sensing of Hg2þ
*
Yanfei Yang, Xiaodan Cao, Malgorzata 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 16 October 2009
Received in revised form 11 November 2009
Accepted 12 November 2009
Available online 15 November 2009
A series of calix[4]arene-dithiacrown-5 and -dithiacrown-6 compounds in cone and 1,3-alternate con-
formations has been synthesized. Responses of these ionophores to Hg2þ and competing metal ions were
determined in solvent polymeric membrane electrodes. High potentiometric selectivity for Hg2þ over
Naþ and a variety of transition and heavy metal ions was obtained.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Calixcrown ligands
Mercury(II) sensor
Ion-selective electrode
Ionophore
1. Introduction
bridges two distal phenolic oxygens. The first example of this ligand
family, p-tert-butylcalix[4]arene-1,3-crown-6, was reported by
Potentiometric methods with ion-selective electrodes (ISE)s of-
fer several advantages, such as ease of preparation and use, rela-
tively rapid response, reasonable selectivity, wide linear dynamic
range and low cost.1,2 A frequently encountered type of ISE is a sol-
vent polymeric membrane electrode. Commonly encountered ISEs
of this type are polyvinyl chloride (PVC)-based membrane elec-
trodes prepared from PVC, a plasticizer, an ionophore and other
components.3
Calixarenes are metacyclophanes composed of phenolic and
methylene units.4–6 They are versatile ionophores, which provide
a platform for attachment of convergent binding groups to create
host molecules primarily for attraction of simple cations, anions
and small molecules. McKervey et al. first recognized that a calix-
arene with cation-complexing groups attached to the lower rim
may possess the molecular requirements for the type of ionophore
used in ISEs.7,8 Tetraesters of calix[4]arene were found to be ex-
cellent ionophores for Naþ in PVC membrane electrodes. This type
of electrode is capable of measuring Naþ in blood.9,10
Ungaro et al. in 1983.17
Replacement of some oxygens in the bridging polyether unit
with sulfurs gives calix[4]arene-thiacrown compounds for which
enhancement of the binding of soft metal ions would be antici-
pated. Only a few calix[4]arene-dithiacrown ethers have been
reported (see compounds 1–5 in Fig. 1).18–23 Within this collection
of ionophores, systematic structural variation is very limited.
We now describe the synthesis and evaluation of a series of
calix[4]arene-dithiacrown compounds 6–11 (Fig. 2). Pairs of iono-
phores 6 and 10 and 7 and 11 are regioisomers in which the con-
formation of the calix[4]arene unit is changed from cone in the
former to 1,3-alternate in the latter. Pairs of ionophores 6 and 8 and
7 and 9 are the same except for variation of the para substituent on
the upper-rim aromatic rings from hydrogen in the former to tert-
butyl in the latter. Finally, pairs of ionophores 6 and 7, 8 and 9, 10
and 11 are the same except for expansion of the dithiacrown-5 ring
in the former to a dithiacrown-6 ring in the latter. Effects of these
systematic structural variations on metal ion responses in PVC
membrane-based electrodes are assessed. For comparison, calix-
[4]arene-crown-6 12 was prepared and examined as well.
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.11–16 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
2. Results and discussion
2.1. Synthesis of new calix[4]arene-dithiacrown ionophores
Preparations of calix[4]arene-dithiacrown ethers 6, 7, 10 and 11
followed a common synthetic route (Scheme 1). Calix[4]arene (13)
* 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.2009.11.058

448
Y. Yang et al. / Tetrahedron 66 (2010) 447–454
Figure 1. Structures of reported calix[4]arene-dithiacrown compounds.
Figure 2. New dibenzyl calix[4]arene-dithiacrown compounds 6–11 and reference dibenzyl calix[4]arene-crown-6 12.
reacted with benzyl bromide and K2CO3 in MeCN at reflux gave the
known cone dibenzyl calix[4]arene 14 in 90% yield. Diether 14 was
treated with NaH and ethyl bromoacetate in THF at room temper-
ature to produce a mixture of the cone dibenzyl diester 15 and the
isomeric 1,3-alternate conformer 16, which was readily separated
by column chromatography on silica gel in yields of 56% and 30%,
respectively. Reactions of dibenzyl diesters 15 and 16 with LAH in
THF at room temperature gave dibenzyl diols 17 (90% yield) and 19
(84% yield), respectively. Attempts to convert these diols into
ditosylates by reaction with TsCl in aqueous THF were unsuccessful.
Therefore mesylates 18 and 20 were prepared by reaction with
MsCl in CH2Cl2 in the presence of Et3N with DMAP as catalyst
according to a literature method.24 The dibenzyl dimesylates were
treated with appropriate dithiols and Cs2CO3 in THF at reflux to
produce the dibenzyl calix[4]arene-dithiacrown ethers 6, 7, 10, and
11 in moderate yields (30–65%) after purification by column chro-
matography on silica gel.
Synthesis of the p-tert-butylcalixarene-dithiacrown ether ana-
logues 8 and 9 followed essentially the same synthetic route
(Scheme 2). Known dibenzyl p-tert-butylcalix[4]arene 22 was
obtained in 90% yield from reaction of p-tert-butylcalix[4]arene
(21) with benzyl bromide and K2CO3 in refluxing MeCN for 24 h.
(Only 1 h at reflux was required in the preparation of 14). Reaction
of dibenzyl ether 22 with NaH and ethyl bromoacetate in THF at
room temperature to form cone dibenzyl diester 23 in 71% yield
took 5–7 days. (This was a much longer reaction period than was
required for conversion of dibenzyl ether 14 into a mixture of
dibenzyl diesters 15 and 16 under the same conditions.). The 1,3-
alternate dibenzyl diester isomer of cone 23 was isolated as
a byproduct in 8% yield. Cone dibenzyl diester 23 was reduced with
LAH in THF at room temperature to produce an 88% yield of cone
dibenzyl diol 24, which was converted into the corresponding cone
dibenzyl dimesylate 25 by reaction with mesyl chloride, Et3N and
DMAP in CH2Cl2 at room temperature. Reaction of 25 with Cs2CO3
and the appropriate dithiol compounds gave cone dibenzyl p-tert-
butylcalix[4]arene-dithiacrown ethers 8 and 9 in low yields of 19%
and 33%, respectively.
For comparison purposes, cone dibenzyl calix[4]arene-crown-6
12 was prepared in 62% yield by reaction of cone calix[4]arene-
crown-6 with NaH and benzyl bromide in THF/DMF at room
temperature.
Structures of new dibenzyl calix[4]arene-dithiacrown ethers
6–11, as well as their previously unreported synthetic in-
termediates 15–17, 19, 23, and 24, were verified by 1H and 13C NMR
spectroscopy, IR spectroscopy (when appropriate) and combustion
analysis. Dimesylate synthetic intermediates 18, 20, and 25 were
characterized only spectroscopically. The structure of new dibenzyl
calix[4]arene-crown-6 12 was confirmed by its 1H and 13C NMR
spectra and combustion analysis.
2.2. Potentiometric responses of solvent polymeric
membrane electrodes
The dibenzyl calix[4]arene-dithiacrown ionophores 6–11 and
dibenzyl calix[4]arene-crown-6 12 (Fig. 2) were incorporated into
solvent polymeric membranes in which PVC was the polymer and

Y. Yang et al. / Tetrahedron 66 (2010) 447–454
449
O
O
O
O
O
O
O
O
O
O
a
b
+
OH
OH
O
O
O
O
O
O
OH
OH
OH
OH
O
O
16
14
15
13
c
c
OH
O
OH
O
d
O
O
O
O
O
O
O
O
O
O
OH
HO
OMs
MsO
17
19
18
e
d
n
O
OMs
O
OMs
S
S
O
O
O
e
O
S
O
O
O
O
O
O
O
S
O
n
n
1
2
n
1
20
6
7
10
11 2
Scheme 1. Synthesis of dibenzyl calix[4]arene-dithiacrown ligands 6, 7, 10, and 11. Reagents and conditions: (a) BnBr, K2CO3, MeCN, reflux; (b) NaH, BrCH2CO2Et, THF, rt; (c) LAH,
THF, rt; (d) MsCl, Et3N, DMAP, CH2Cl2, rt; (e) HSCH2CH2(OCH2CH2)nSH, (n¼1, 2), Cs2CO3, THF, reflux.
NPOE was the membrane solvent. For the ion-selective electrodes
(ISEs) prepared from these membranes, selectivities for Hg2þ rel-
ative to Naþ and the divalent transition and heavy metal ion series
of Cd2þ, Co2þ, Cu2þ, Ni2þ, Pb2þ, and Zn2þ were determined by the
fixed interference method.25 Near-Nerstian responses (20–30 mV/
decade) were obtained for all of the solvent polymeric membranes.
Ionophores 7 and 9 showed Nerstian responses of 29.5 mV/decade.
ISEs prepared with calix[4]arene-dithiacrown compounds 6–11
were selective for Hg2þ over all of the other metal ions tested. The
ISE prepared with calix[4]arene-crown-6 12 was selective for Hg2þ
over all of the divalent metal ions, but exhibited slight selectivity
Cone dibenzyl calix[4]arene-crown-6 12 is a reference com-
pound with only oxygen atoms in the crown ether unit. The se-
lectivity order for the ISE incorporating this ionophore is
Naþ>Hg2þ>>Pb2þwCd2þ>Ni2þwCu2þ>Co2þ>Zn2þ. Replacement
of two oxygens in the crown unit of 12 with sulfurs gives cone
dibenzyl calix[4]arene-dithiacrown-6 7. This structural variation
produces a marked change in the potentiometric selectivities of the
ISEs toward Hg2þ giving ꢀlog KHg,M values of 2.2–3.6 for the di-
valent transition and heavy metal ions, as well as for Naþ.
With this substitution, the selectivity order changes
to Hg2þ>>>Pb2þ>Cd2þ>Naþ, Zn2þ>Cu2þwCo2þ>Ni2þ
.
In-
Pot
for Naþ over Hg2þ. Selectivity coefficients expressed as ꢀlog K
corporation of two soft ligation sites in the crown ring of 7 mark-
Hg,M
values for Hg2þ over other divalent transition and heavy metal ions
edly enhances the Hg2þ selectivity.
Pot
and Naþ are presented in Table 1. (A larger value of ꢀlog K
Replacement of the para hydrogens on the upper-rim aryl rings
of cone dibenzyl calix[4]arene-dithiacrown-6 7 with tert-butyl
Hg,M
denotes a greater Hg2þ selectivity).

450
Y. Yang et al. / Tetrahedron 66 (2010) 447–454
c
a
b
O
O
O
O
O
O
O
O
OH
OH
O
O
OH
OH
OH
O
O
OH
OH
HO
O
O
24
21
22
23
n
1
d
e
8
9
O
O
O
O
O
S
O
S
O
O
2
OMs
MsO
O
n
25
Scheme 2. Synthesis of dibenzyl p-tert-butylcalix[4]arene-dithiacrown ligands 8 and 9. Reagents and conditions: (a) BnBr, K2CO3, MeCN, reflux; (b) NaH, BrCH2CO2Et, THF, rt;
(c) LAH, THF, rt; (d) MsCl, Et3N, DMAP, CH2Cl2, rt; (e) HSCH2CH2(OCH2CH2)nSH, (n¼1, 2), Cs2CO3, THF, reflux.
which has both a smaller dithiacrown-5 ring and a 1,3-alternate
Table 1
conformation of the calix[4]arene scaffold.
Pot a,b
Potentiometric selectivities (ꢀlog K
)
of compounds 6–12 as ionophores in
Hg,M
Of the six new dibenzyl calix[4]arene-dithiacrown compounds
6–11, the ISE prepared with ionophore 7 provides the highest Hg2þ
selectivity over the six divalent transition and heavy metal cations
and Naþ.
solvent polymeric membrane electrodes
Pot
Ionophore
ꢀlog K
Naþ
Hg,M
Cd2þ
Co2þ
Cu2þ
Ni2þ
Pb2þ
Zn2þ
6
7
8
9
10
11
12
2.27
3.11
2.16
3.04
1.23
2.04
0.80
1.88
2.42
1.81
2.26
1.90
2.98
1.84
2.94
3.473
2.72
3.28
1.20c
2.96
2.71
2.26
39
3.09
3.56
1.24
3.55
0.96
2.98
2.52
1.76
2.21
1.70
2.13
1.52
2.28
1.74
2.75
3.11
2.76
3.13
1.63
2.74
2.79
1.77c
3.39
0.98
2.92
2.60
3. Experimental
3.1. General
Melting points were determined with a Mel-Temp apparatus.
Infrared (IR) spectra were recorded with a Nicolet IR100 FTIR
spectrometer as deposits from CH2Cl2 solutions on NaCl plates
unless otherwise mentioned. The 1H and 13C NMR spectra were
recorded with a Varian Unity INOVA 500 MHz FTNMR spectrometer
at 500 and 126 MHz, respectively, in CDCl3 with Me4Si as internal
a
Pot
The primary ion, Hg2þ, corresponds to a ꢀlog K
Standard deviation of 0.05 or less.
value of 0.
Hg,M
b
c
Poor electrode stability was observed.
groups produces cone dibenzyl tert-butylcalix[4]arene-dithia-
crown-6 9. Comparison of the data for ISEs containing ionophores 7
and 9 in Table 1 reveals very similar potentiometric selectivities for
the two ligands. Thus this structural variation is judged to have only
a small effect, if any, on the Hg2þ selectivity.
standard, unless mentioned otherwise. Chemical shifts (d) are given
in ppm downfield from TMS and coupling constants values (J) are
given in Hertz. Elemental analysis was performed by Desert Ana-
lytics Laboratory/Columbia Analytical Services (Tucson, Arizona).
Reagents were purchased from commercial suppliers and
used directly unless otherwise noted. Calix[4]arene (13) and
p-tert-butylcalix[4]arene (21) were obtained from Eburon
Organics International, Inc. (Lubbock, Texas). Acetonitrile (MeCN)
was dried over CaH2 and distilled immediately before use. Tet-
rahydrofuran (THF) was dried over sodium with benzophenone
as an indicator and distilled just before use.
For the potentiometric studies, KCl (99%) and NaCl (99%) were
purchased from Sigma–Aldrich (Milwaukee, Wisconsin). Cd(NO3)2,
Co(NO3)2$6H2O (99þ%), Cu(NO3)2, Hg(NO3)2, and Ni(NO3)2$6H2O
were obtained from Acros Organics (Morris Plains, New Jersey).
Pb(NO3)2 and Zn(NO3)2 were purchased from MCB (Norwood,
Ohio) and Fisher Scientific (Fair Lawn, New Jersey), respectively.
High molecular weight poly(vinyl chloride) (PVC) with an average
Dibenzyl calix[4]arene-dithiacrown-6 ionophores 7 and 11 are
isomers in which the calix[4]arene scaffold is cone in the former
and 1,3-alternate in the latter. Potentiometric selectivities for ISEs
containing these two ionophores show high Hg2þ selectivities for
Pot
both ionophores. When taken together, the ꢀlog K
values for
Hg,M
the cone isomer (2.2–3.6) appear to be slightly higher than those
for the 1,3-alternate isomer (2.0–3.0). This result suggests that the
primary binding of Hg2þ is by the crown ring, rather than cation–
interactions with the calixarene unit.
p
Contraction of the crown ring in ionophores 7, 9, and 11 from
dithiacrown-6 to dithiacrown-5 in ionophores 6, 8, and 10, re-
spectively, uniformly decreases the potentiometric selectivity for
Hg2þ. The least selective ISE was that prepared from ionophore 10,

Y. Yang et al. / Tetrahedron 66 (2010) 447–454
451
polymerization degree of 1100 was obtained from Wako Pure
Chemical Industries (Osaka, Japan). Potassium tetrakis(p-chloro-
phenyl)borate (KTpClPB) and ortho-nitrophenyl octyl ether (NPOE)
were purchased from Dojindo Laboratories (Kumamoto, Japan). De-
ionized water was prepared by passing distilled water through
three Barnsted combination ion-exchange cartridges in series and
used to prepare aqueous solutions and rinse plastic bottles and
glassware during the experiment.
OCH2CH3), 3.48 (s, 4H, OCH2Ar), 3.60 (d, J¼14.5 Hz, 4H, ArCH2Ar),
3.90 (d, J¼14.5 Hz, 4H, ArCH2Ar), 4.16 (q, J¼7.0 Hz, 4H, OCH2CH3),
4.86 (s, 4H, OCH2C(O)), 6.40 (t, J¼7.5 Hz, 2H, ArH), 6.70 (d, J¼8.0 Hz,
4H, ArH), 6.79 (t, J¼7.5 Hz, 2H, ArH), 7.13 (d, J¼6.5 Hz, 4H, ArH), 7.17
(d, J¼7.5 Hz, 4H, ArH), 7.35–7.41 (m, 6H, ArH). 13C NMR:
d 14.2, 37.1,
60.4, 68.9, 72.8, 122.4, 123.0, 127.2, 127.2, 127.9, 130.4, 131.3, 133.4,
134.8, 137.7, 155.0, 156.8, 170.0. Anal. calcd for C50H48O8: C, 77.30; H,
6.23%. Found: C, 77.26; H, 6.31%.
3.2. Ligand synthesis
3.2.4. Cone25,27-bis(benzyloxy)-26,28-bis(2-hydroxy-ethoxy)calix[4]-
arene (17). Dibenzyl diester 15 (1.00 g, 1.29 mmol) was dissolved in
THF (50 mL). To the solution, LAH (0.15 g, 3.87 mmol) was added
and the mixture was stirred at room temperature for 48 h. Careful
addition of distilled water (0.15 mL) was followed by aq 10% NaOH
(0.15 mL) and then distilled water (0.45 mL). The mixture was
stirred for 15 min at room temperature and the precipitate was
filtered. After evaporation of the THF in vacuo, CH2Cl2 (50 mL) and
aq 10% HCl (50 mL) were added to the residue. The organic layer
was separated, washed with water (2ꢂ50 mL), dried over MgSO4
and evaporated in vacuo to give cone diol 17 (0.84 g, 90%) as a white
3.2.1. Cone 25,27-bis(benzyloxy)calix[4]arene (14). A mixture of
calix[4]arene (13) (10.00 g, 23.60 mmol) and K2CO3 (3.90 g,
28.3 mmol) in MeCN (350 mL) was refluxed for 1 h under nitrogen.
Benzyl bromide (8.90 g, 51.90 mmol) was added in one portion and
the mixture was refluxed for 1 h. The mixture was poured into ice
cold 1 N aq HCl. The precipitate was filtered and recrystallized from
CH2Cl2–MeOH to give 14 (13.80 g, 90%) as white crystals with mp
224–225 ꢁC (lit. mp26 219–222 ꢁC). 1H NMR:
d
3.34 (d, J¼13.0 Hz,
4H, ArCH2Ar), 4.31 (d, J¼13.0 Hz, 4H, ArCH2Ar), 5.06 (s, 4H,
OCH2Ph), 6.65 (t, J¼8.0 Hz, 2H, ArH), 6.75 (t, J¼8.0 Hz, 2H, ArH),
6.89 (d, J¼8.0 Hz, 4H, ArH), 7.05 (d, J¼8.0 Hz, 4H, ArH), 7.34–7.40
(m, 6H, ArH), 7.64–7.66 (m, 4H, ArH), 7.81 (s, 2H, OH). 13C NMR:
solid with mp 178–179 ꢁC. IR: 3426 (OH) cmꢀ1. 1H NMR:
d 2.89 (d,
J¼14.0 Hz, 4H, ArCH2Ar), 3.77–3.80 (m, 4H, OCH2CH2OH), 4.07–4.08
(m, 4H, OCH2CH2OH), 4.21 (d, J¼13.5 Hz, 4H, ArCH2Ar), 4.83–4.85
(m, 6H, OH, OCH2Ar), 6.14 (d, J¼7.5 Hz, 4H, ArH), 6.26 (t, J¼7.5 Hz,
2H, ArH), 6.94 (t, J¼7.5 Hz, 2H, ArH), 7.08 (d, J¼7.5 Hz, 4H, ArH),
d
31.4, 78.4, 118.9, 125.4, 127.4, 127.9, 128.0 128.4, 128.7, 129.0, 133.2,
136.8, 151.9, 153.3.
7.27–7.36 (m, 10H, ArH). 13C NMR:
d 30.7, 61.6, 77.1, 78.2, 122.8,
3.2.2. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis(benzyl-
oxy)calix[4]arene (22). Under the same conditions as given above
for the preparation of 14, but with refluxing of the reaction mixture
for 24 h, p-tert-butylcalix[4]arene (21) (10.00 g, 15.43 mmol), K2CO3
(2.55 g, 18.52 mmol), and benzyl bromide (5.82 g, 33.95 mmol) in
MeCN (350 mL) were combined to produce 22 (11.50 g, 90%) as
a white solid with mp 220–221 ꢁC (lit. mp26 219–220 ꢁC). 1H NMR:
122.9, 127.7,128.3, 128.5, 129.1, 130.0, 133.2,136.0, 136.7, 152.6, 157.1.
Anal. calcd for C48H48O6$0.2CH2Cl2: C, 78.46; H, 6.61%. Found: C,
78.65; H, 6.81%.
3.2.5. 1,3-Alternate 25,27-bis(benzyloxy)-26,28-bis(2-hydroxy-eth-
oxy)calix[4]arene (19). The procedure for synthesizing 19 from 16
was the same as that given above for preparation of 17 from 15. The
1,3-alternate dibenzyl diol 19 was obtained in 84% yield as a white
d
0.94 (s, 18H, C(CH3)3), 1.28 (s, 18H, C(CH3)3), 3.26 (d, J¼13.0 Hz, 4H,
ArCH2Ar), 4.28 (d, J¼13.0 Hz, 4H, ArCH2Ar), 5.05 (s, 4H, OCH2Ar),
solid with mp 152–154 ꢁC. IR: 3399 (OH) cmꢀ1. 1H NMR:
d 2.30 (t,
6.68 (s, 4H, ArH), 7.04 (s, 4H, ArH), 7.30 (s, 2H, OH), 7.35–7.37 (m, 6H,
J¼6.5 Hz, 2H, OH), 3.46–3.49 (m, 4H, OCH2CH2OH), 3.63–3.77 (m,
12H, OCH2CH2OH, ArCH2Ar), 4.74 (s, 4H, OCH2Ar), 6.39 (t, J¼7.5 Hz,
2H, ArH), 6.68 (d, J¼8.0 Hz, 4H, ArH), 6.91–6.94 (m, 6H, ArH), 7.12
ArH), 7.64–7.66 (m, 4H, ArH). 13C NMR:
d 31.0, 31.4, 31.6, 31.7, 33.8,
33.9, 77.9, 124.9, 125.0, 125.5, 127.3, 127.5, 127.8, 127.9, 128.6, 129.6,
132.6, 133.8, 137.2, 141.3, 146.9, 149.8, 150.8.
(d, J¼7.5 Hz, 4H, ArH), 7.26–7.33 (m, 6H, ArH). 13C NMR:
d 38.0, 61.4,
71.1, 72.1, 122.9, 122.9, 127.1, 127.5, 127.7, 129.7, 130.2, 133.4, 134.4,
137.6, 155.5, 156.6. Anal. calcd for C48H48O6$0.1CH2Cl2: C, 79.21; H,
6.66%. Found: C, 78.87; H, 6.70%.
3.2.3. Cone 25,27-bis(benzyloxy)-26,28-bis[((ethoxycarbonyl)meth-
oxy)]calix[4]arene (15) and 1,3-alternate 25,27-bis(benzyloxy)-26,28-
bis[((ethoxycarbonyl)methoxy)]calix[4]arene (16). Dibenzyl calix[4]-
arene 14 (4.00 g, 6.62 mmol) was stirred with NaH (1.59 g,
66.20 mmol) in THF (200 mL) for 1 h and ethyl bromoacetate
(3.87 g, 23.17 mmol) was added in one portion. The mixture was
stirred at room temperature overnight and then reaction was
quenched by addition of small amount of water. After evaporation
of the THF in vacuo, CH2Cl2 (150 mL) and aq 1 N HCl (150 mL) were
added to the residue. The organic layer was separated, washed with
water (2ꢂ250 mL), dried over MgSO4 and evaporated in vacuo to
give the crude product, which was chromatographed on silica gel
with hexanes–EtOAc (50:1 to 4:1 gradient) as eluent to give 15 as
the major product (2.90 g, 56%) and 16 as the minor product (1.50 g,
30%).
3.2.6. Cone 25,27-bis(benzyloxy)-26,28-bis(2-mesyloxyethoxy)calix-
[4]arene (18). A solution of diol 17 (0.72 g, 1.00 mmol), Et3N (1.01 g,
10.00 mmol), DMAP catalyst (0.20 g) in CH2Cl2 (50 mL) was stirred
at 0 ꢁC for 30 min. MsCl (1.14 g, 10.00 mmol) was added in one
portion and stirring was continued overnight, first at 0 ꢁC and then
eventually allowing it to warm up to room temperature. The mix-
ture was washed with aq 1 N HCl (2ꢂ50 mL) and water (2ꢂ50 mL)
and dried over MgSO4. After evaporation of the CH2Cl2 in vacuo, the
crude product was purified by chromatography on silica gel with
hexanes–EtOAc (50:1 to 4:1 gradient) as eluent to give cone
dibenzyl dimesylate 18 (0.61 g, 70%) as a white solid with mp
189–191 ꢁC. 1H NMR:
d
2.67 (s, 6H, CH3SO2), 3.12 (d, 4H, J¼14.0 Hz,
Cone dibenzyl diester 15 was a white solid with mp 125–126 ꢁC.
ArCH2Ar), 4.24 (t, J¼6.0 Hz, OCH2CH2OMs), 4.32 (d, J¼13.5 Hz,
ArCH2Ar), 4.41 (t, J¼6.5 Hz, OCH2CH2OMs), 4.74 (s, 4H, OCH2Ar),
6.17 (d, J¼7.5 Hz, 4H, ArH), 6.29 (t, J¼7.0 Hz, 2H, ArH), 6.94 (t,
J¼7.5 Hz, 2H, ArH), 7.08 (d, J¼7.5 Hz, 4H, ArH), 7.33–7.47 (m, 10H,
IR: 1759, 1734 (C]O) cmꢀ1
.
1H NMR:
d
1.20 (t, J¼7.0 Hz, 6H,
OCH2CH3), 3.09 (d, J¼14.0 Hz, 4H, ArCH2Ar), 4.07 (q, J¼7.5 Hz, 4H,
OCH2CH3), 4.52 (d, J¼13.0 Hz, 4H, ArCH2Ar), 4.55 (s, 4H, OCH2Ar),
5.03 (s, 4H, OCH2C(O)), 6.44–6.52 (m, 6H, ArH), 6.66–6.75 (m, 6H,
ArH), 7.29–7.31 (m, 6H, ArH), 7.43–7.45 (m, 4H, ArH). 13C NMR:
ArH). 13C NMR:
d 31.0, 37.3, 68.2, 71.0, 77.9, 122.7, 123.0, 127.8, 128.3,
128.7, 129.1, 129.3, 133.0, 136.3, 137.1, 154.1, 157.0.
d
14.2, 31.3, 60.4, 70.7, 76.9, 122.5, 122.6, 127.7, 128.0, 128.0, 128.7,
129.3, 134.7, 135.2, 137.8, 155.1, 156.0, 170.0. Anal. calcd for
C50H48O8: C, 77.30; H, 6.23%. Found: C, 77.03; H, 6.36%.
3.2.7. 1,3-Alternate 25,27-bis(benzyloxy)-26,28-bis(2-mesyloxyeth-
oxy)calix[4]arene (20). The procedure given above for preparing 18
from 17 was utilized to convert 19 into 20. The 1,3-alternate
dibenzyl dimesylate 20 was obtained in 72% yield as a white solid
The 1,3-alternate dibenzyl diester 16 was a white solid with mp
120–121 ꢁC. IR: 1756 (C]O) cmꢀ1. 1H NMR:
d
1.27 (t, J¼7.0 Hz, 6H,

452
Y. Yang et al. / Tetrahedron 66 (2010) 447–454
with mp 172–174 ꢁC. 1H NMR:
d
2.56 (s, 6H, CH3SO2), 3.68 (s, 8H,
ArH).13C NMR:
d 31.6, 32.8, 37.7, 70.8, 71.0, 71.7, 72.0, 122.4, 122.5,
ArCH2Ar), 3.81 (t, J¼4.5 Hz, OCH2CH2OMs), 4.27 (t, J¼4.5 Hz,
OCH2CH2OMs), 4.81 (s, 4H, OCH2Ar), 6.38 (t, J¼7.5 Hz, 2H, ArH),
6.67 (d, J¼7.5 Hz, 4H, ArH), 7.01–7.05 (m, 6H, ArH), 7.16 (d, J¼7.5 Hz,
127.0, 127.1, 127.8, 129.9, 130.6, 133.4, 134.4, 137.9, 155.7, 156.6.
Anal. calcd for C52H54O6S2: C, 74.43; H, 6.49. Found: C, 74.10; H,
6.73%.
4H, ArH), 7.37–7.41 (m, 6H, ArH). 13C NMR:
d 37.4, 37.6, 68.3, 68.7,
72.2, 123.1, 123.5, 127.1, 127.2, 127.8, 130.2, 131.5, 133.2, 134.9, 137.4,
155.0, 156.9.
3.2.9. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis(benzyl-
oxy)-26,28-bis[((ethoxy-carbonyl)methoxy)]calix[4]arene (23) and
1,3-alternate 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis(benzyl-
oxy)-26,28-bis[((ethoxycarbonyl)methoxy)]calix[4]arene. After a mix-
ture of dibenzyl p-tert-butylcalix[4]arene 22 (4.00 g, 4.82 mmol) and
NaH (1.16 g, 48.20 mmol) in THF (200 mL) was stirred at room
temperature for 1 h, ethyl bromoacetate (2.82 g, 16.87 mmol) was
added in one portion and the mixture was stirred at room temper-
ature overnight. After evaporation of the THF in vacuo, CH2Cl2
(150 mL) and aq 1 N HCl (150 mL) were added to the residue. The
organic layer was separated, washed with water (2ꢂ250 mL), dried
over MgSO4 and evaporated in vacuo to give the crude product,
which was chromatographed on silica gel with hexanes–EtOAc (50:1
to 4:1 gradient) as eluent to give 23 as the major product (3.43 g,
71%) and a small amount (0.35 g, 8%) of a byproduct. Cone dibenzyl
diester 23 was a white solid with mp 167–169 ꢁC. IR: 1760 (C]O)
3.2.8. General procedure for synthesis of calix[4]arene-dithiacrown
ligands 6, 7, 10, and 11. Dibenzyl calix[4]arene dimesylate 18 or 20
(0.85 g, 1.00 mmol) was mixed with Cs2CO3 (1.63 g, 5.00 mmol) in
THF (75 mL). The appropriate dithiol (1.10 mmol) was mixed with
THF (10 mL) and the solution was added to the mixture during a 3 h
period. The mixture was refluxed for 72 h and the THF was removed
in vacuo. To the residue, CH2Cl2 (50 mL) and aq 1 N HCl (50 mL)
were added. The organic layer was separated, washed with water
(2ꢂ50 mL), dried over MgSO4 and evaporated in vacuo to give the
crude product. The crude product was purified by chromatography
on silica gel with hexanes–EtOAc (50:1 to 4:1 gradient) as eluent to
give the dibenzyl calix[4]arene-dithiacrown compound.
3.2.8.1. Cone 25,27-bis(benzyloxy)calix[4]arene-dithiacrown-
5. Compound 6 was obtained in 53% yield as a white solid with mp
cmꢀ1
.
1H NMR:
d
0.96 (s, 18H, C(CH3)3), 1.18 (t, J¼7.0 Hz, 6H,
OCH2CH3), 1.19 (s, 18H, C(CH3)3), 3.09 (d, J¼13.0 Hz, 4H, ArCH2Ar),
4.01 (q, J¼7.0 Hz, 4H, OCH2CH3), 4.56 (d, J¼13.0 Hz, 4H, ArCH2Ar).
4.58 (s, 4H, OCH2Ar), 4.94 (s, 4H, OCH2C(O)), 6.60 (s, 4H, ArH), 6.90 (s,
4H, ArH), 7.31–7.34 (m, 6H, ArH), 7.46–7.48 (m, 4H, ArH). 13C NMR:
266–267 ꢁC. 1H NMR:
d
2.23 (t, J¼7.0 Hz, 4H, SCH2CH2O), 2.70 (t,
J¼8.0 Hz, 4H, SCH2CH2O), 3.19–3.24 (m, 8H, ArCH2Ar, OCH2CH2S),
4.06 (t, J¼8.0 Hz, OCH2CH2S), 4.47 (d, J¼13.0 Hz, 4H, ArCH2Ar), 4.67
(s, 4H, OCH2Ar), 6.16 (d, J¼8.0 Hz, 4H, ArH), 6.26 (t, J¼7.0 Hz, 2H,
ArH), 6.97 (t, J¼8.0 Hz, 2H, ArH), 7.16 (d, J¼8.0 Hz, 4H, ArH), 7.36–
d
14.1, 31.2, 31.5, 31.9, 33.7, 60.1, 70.3, 77.3, 124.8, 125.4, 127.6, 128.0,
129.2, 132.9, 134.3, 138.3, 144.6, 145.0, 152.6, 153.1, 170.6. Anal. calcd
for C66H80O8$0.1CH2Cl2: C, 78.62; H, 8.00%. Found: C, 78.70; H, 8.29%.
The 1,3-alternate dibenzyl diester isomer byproduct was a white
7.56 (m, 10H, ArH). 13C NMR:
d 29.8, 30.4, 31.1, 70.7, 73.9, 77.9, 122.6,
122.6, 127.6, 128.3, 128.8, 129.1, 129.3, 132.9, 137.0, 137.5, 154.4,
156.4. Anal. calcd for C50H50O5S2: C, 75.53; H, 6.34; S, 8.07%. Found:
C, 75.20; H, 6.64; S, 8.13%.
solid with mp 208–209 ꢁC. IR: 1760 (C]O) cmꢀ1. 1H NMR:
d 0.86 (s,
18H, C(CH3)3), 1.19 (t, J¼7.0 Hz, 6H, OCH2CH3), 1.25 (s, 18H, C(CH3)3),
3.57 (d, J¼16.0 Hz, 4H, ArCH2Ar), 3.58 (s, 4H, OCH2Ar), 3.97 (d,
J¼13.0 Hz, 4H, ArCH2Ar), 4.08 (q, J¼7.5 Hz, 4H, OCH2CH3), 4.53 (s,
4H, OCH2C(O)), 6.74 (s, 4H, ArH), 6.95–6.97 (m, 4H, ArH), 7.13 (s, 4H,
3.2.8.2. Cone 25,27-bis(benzyloxy)calix[4]arene-dithiacrown-
6. Compound 7 was isolated in 30% yield as a white solid with mp
158–160 ꢁC. 1H NMR:
d
2.47 (t, J¼7.0 Hz, 4H, SCH2CH2O), 2.86 (t,
ArH), 7.22–7.24 (m, 6H, ArH). 13C NMR:
d 31.0, 31.4, 33.5, 33.9, 38.6,
J¼8.0 Hz, 4H, SCH2CH2O), 3.13 (d, J¼13.0 Hz, 4H, ArCH2Ar), 3.56 (t,
J¼7.0 Hz, 4H, OCH2CH2S), 3.58 (s, 4H, OCH2CH2O), 4.09 (t, J¼8.0 Hz,
OCH2CH2S), 4.43 (d, J¼13.0 Hz, 4H, ArCH2Ar), 4.72 (s, 4H, OCH2Ar),
6.12 (d, J¼8.0 Hz, 4H, ArH), 6.25 (t, J¼7.0 Hz, 2H, ArH), 6.95 (t,
J¼8.0 Hz, 4H, ArH), 7.13 (d, J¼8.0 Hz, 4H, ArH), 7.36 (t, J¼8.0 Hz, 2H,
ArH), 7.41 (t, J¼7.0 Hz, 4H, ArH), 7.48 (t, J¼7.0 Hz, 4H, ArH). 13C
60.3, 68.5, 73.0, 126.8, 127.1, 127.2, 127.7, 128.0, 133.1, 134.0, 138.2,
144.3, 144.9, 153.3, 154.3, 170.2. Anal. calcd for C66H80O8$0.1CH2Cl2:
C, 78.62; H, 8.00%. Found: C, 78.33; H, 8.17%.
3.2.10. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis(benzyl-
oxy)-26,28-bis(2-hydroxy-ethoxy)calix[4]arene (24). The pro-
cedure for converting compound 23 into 24 was the same as
that given above for the preparation of compound 17 from 15.
The dibenzyl diol 24 was obtained in 88% yield as a white solid
NMR: d 31.1, 31.2, 31.5, 70.6, 71.0, 73.5, 77.7,122.4,122.6,127.6,128.2,
128.6, 128.9, 129.1, 129.1, 133.0, 136.8, 137.4, 154.3, 157.2. Anal. calcd
for C52H54O6S2: C, 74.43; H, 6.49; S, 7.64%. Found: C, 74.23; H, 7.03;
S, 7.65%.
with mp 228–230 ꢁC. IR: 3449 (OH) cmꢀ1 1H NMR:
. d 0.81 (s,
18H, C(CH3)3), 1.31 (s, 18H, C(CH3)3), 2.87 (d, J¼12.5 Hz, 4H,
ArCH2Ar), 3.83–3.86 (m, 4H, OCH2CH2OH), 3.96–3.98 (m, 4H,
OCH2CH2OH), 4.16 (d, J¼12.5 Hz, 4H, ArCH2Ar), 4.81 (s, 4H,
OCH2Ar), 5.06 (t, J¼6.5 Hz, 2H, OH), 6.44 (s, 4H, ArH), 7.06 (s,
3.2.8.3. 1,3-Alternate 25,27-bis(benzyloxy)calix[4]arene-dithia-
crown-5. Compound 10 was produced in 48% yield as a white solid
with mp 141–142 ꢁC. 1H NMR:
d
2.42 (t, J¼8.0 Hz, 4H, SCH2CH2O),
2.66 (t, J¼6.0 Hz, 4H, SCH2CH2O), 3.51 (t, J¼7.0 Hz, 4H, OCH2CH2S),
3.65–3.77 (m, 12H, OCH2CH2S, ArCH2Ar), 4.70 (s, 4H, OCH2Ar), 6.36
(t, J¼8.0 Hz, 2H, ArH), 6.65 (d, J¼8.0 Hz, 4H, ArH), 6.90–6.93 (m, 6H,
ArH), 7.15 (d, J¼7.0 Hz, 4H, ArH), 7.24–7.29 (m, 6H, ArH). 13C NMR:
4H, ArH), 7.25–7.33 (m, 10H, ArH). 13C NMR:
d 30.8, 31.1, 31.7,
33.6, 34.1, 61.7, 76.8, 78.3, 124.6, 125.6, 128.1, 128.3, 130.4, 132.2,
135.4, 136.4, 145.0, 145.5, 150.1, 153.8. Anal. calcd for C62H76O6:
C, 81.18; H, 8.35%. Found: C, 80.99; H, 8.36%.
d
32.8, 33.2, 38.0, 69.6, 72.0, 73.1, 122.6, 122.6, 127.0, 127.3, 127.7,
129.5, 130.0, 133.5, 134.4, 137.9, 155.6, 156.8. Anal. calcd for
C50H50O5S2: C, 75.53; H, 6.34; S, 8.07%. Found: C, 75.55; H, 6.48; S,
8.24%.
3.2.11. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis(benzyl-
oxy)-26,28-bis(2-mesyloxy-ethoxy)calix[4]arene (25). The pro-
cedure for preparing compound 25 from 24 was the same as that
given above for the synthesis of 18 from 17. The dibenzyl dime-
sylate 25 was obtained in 84% yield as a white solid with mp 168–
171 ꢁC after chromatography on silica gel with hexanes–EtOAc
3.2.8.4. 1,3-Alternate
crown-6. Compound 11 was realized in 65% yield as a white solid
with mp 124–126 ꢁC. 1H NMR:
25,27-bis(benzyloxy)calix[4]arene-dithia-
d
2.52 (t, J¼8.0 Hz, 4H, SCH2CH2O),
(50:1 to 4:1 gradient) as eluent. 1H NMR:
d 0.82 (s, 18H, C(CH3)3),
2.62 (t, J¼6.0 Hz, 4H, SCH2CH2O), 3.63–3.76 (m, 20H, ArCH2Ar,
OCH2CH2O, OCH2CH2S), 4.76 (s, 4H, OCH2Ar), 6.38 (t, J¼8.0 Hz, 2H,
ArH), 6.65 (d, J¼8.0 Hz, 4H, ArH), 6.88 (t, J¼8.0 Hz, 2H, ArH), 7.00–
7.02 (m, 4H, ArH), 7.15 (d, J¼8.0 Hz, 4H, ArH), 7.31–7.34 (m, 6H,
1.32 (s, 18H, C(CH3)3), 2.75 (s, 6H, SO2CH3), 3.04 (d, J¼13.0 Hz, 4H,
ArCH2Ar), 4.18 (t, J¼6.5 Hz, 4H, OCH2CH2OMs), 4.22 (d,
J¼12.5 Hz, 4H, ArCH2Ar), 4.51 (t, J¼6.5 Hz, 4H, OCH2CH2OMs),
4.76 (s, 4H, OCH2Ar), 6.44 (s, 4H, ArH), 7.08 (s, 4H, ArH), 7.33–7.43

Y. Yang et al. / Tetrahedron 66 (2010) 447–454
453
(m, 10H, ArH). 13C NMR:
70.5, 78.3, 124.7, 125.6, 128.2, 128.6, 129.8, 131.8, 135.2, 137.3,
144.7, 145.9, 151.5, 153.6.
d
31.0, 31.2, 31.6, 33.6, 34.1, 37.3, 68.3,
polytetrafluorethylene (PTFE) membrane support (Analyticon In-
struments Corporation, Springfield, New Jersey) was dipped first in
THF and then in the membrane preparation cocktail. The mem-
brane support was transferred to the top opening of a hollow blank
cap for the 7901 L electrode (Analyticon Instruments Corporation,
Springfield, New Jersey). The membrane preparation cocktail was
cast on the PTFE membrane support by adding two drops every
30 min with a 1-mL glass microsyringe. Addition of the solution
and evaporation of the THF was performed six times. Further
evaporation of the THF at room temperature overnight yielded an
elastic, translucent membrane of approximately 0.3 mm thickness.
The resulting PVC cap with the coated PTFE membrane was fixed on
a Denki Kagaku Keiki (DDK, Musashino, Tokyo, Japan) No. 7900
electrode body containing a AgCl wire as an internal reference
electrode. An internal filling solution of 0.10 M Hg(NO3)2 was added
to the electrode. The membrane electrode was conditioned by
soaking in 0.10 M Hg(NO3)2 for 24 h before use. For each ionophore,
two membrane electrodes were prepared.
3.2.12. General procedure for preparation of p-tert-butylcalix[4]arene-
dithiacrown ligands 8 and 9. The procedure for preparing com-
pounds 8 and 9 from 25 was essentially the same as that employed
for the preparation of compounds 6 and 7 from 18.
3.2.12.1. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis(ben-
zyloxy)calix[4]arene-dithiacrown-5. Compound 8 was obtained in
19% yield after chromatography on silica gel with hexanes–EtOAc
(50:1 to 4:1 gradient) as eluent. It was a white solid that decom-
posed at 272 ꢁC before melting. 1H NMR:
d 0.82 (s, 18H, C(CH3)3),
1.35 (s, 18H, C(CH3)3), 2.22 (t, J¼7.5 Hz, 4H, SCH2CH2O), 2.81–2.84
(m, 4H, SCH2CH2O), 3.14 (d, J¼12.5 Hz, 4H, ArCH2Ar), 3.24 (t,
J¼7.5 Hz, 4H, OCH2CH2S), 3.99–4.03 (m, 4H, OCH2CH2S), 4.43 (d,
J¼12.5 Hz, 4H, ArCH2Ar), 4.64 (s, 4H, OCH2Ar), 6.44 (s, 4H, ArH), 7.13
(s, 4H, ArH), 7.35–7.52 (m, 10H, ArH). 13C NMR:
d 30.4, 30.5, 31.1,
31.3, 31.7, 33.6, 34.1, 70.9, 73.8, 78.4, 124.6, 125.7, 128.3, 128.8, 129.9,
131.7, 135.7, 137.6, 144.6, 145.3, 152.2, 153.6. Anal. calcd for
C66H82O5S2: C, 77.76; H, 8.11; S, 6.29%. Found: C, 77.38; H, 7.90; S,
5.95%.
3.3.2. Potentiometric measurements. Potentiometric measure-
ments with a membrane electrode were carried out at room tem-
perature with a voltage meter (Fisher Scientific, Accumet 50 pH
meter), a double junction Ag–AgCl reference electrode (DDK No.
4083), and a magnetic stirrer to agitate the sample solution. The
electrode cell was Ag–AgCl/4.0 M KCl/sample solution/PVC mem-
3.2.12.2. Cone 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-bis(ben-
zyloxy)calix[4]arene-dithiacrown-6. Compound 9 was isolated in
33% yield after chromatography on silica gel with hexanes–EtOAc
(50:1 to 4:1 gradient) as eluent. It was a white solid with mp 240–
brane/0.10 M Hg(NO3)2/Ag/AgCl (CHECK). Selectivity coefficients
Pot
(K
) were determined by the fixed interference method.25 The
Hg,M
background concentrations of the interference ions were 10 mM
Naþ, Cd2þ, Co2þ, Cu2þ, Ni2þ, Pb2þ, and Zn2þ. Concentrations of Hg2þ
,
242 ꢁC. 1H NMR:
d
0.81 (s, 18H, C(CH3)3), 1.33 (s, 18H, C(CH3)3), 2.56
(t, J¼6.5 Hz, 4H, SCH2CH2O), 2.92–2.95 (m, 4H, SCH2CH2O), 3.03 (d,
J¼12.5 Hz, 4H, ArCH2Ar), 3.67–3.69 (m, 8H, OCH2CH2O, SCH2CH2O),
3.98–4.01 (m, 4H, OCH2CH2S), 4.32 (d, J¼12.5 Hz, 4H, ArCH2Ar),
4.71 (s, 4H, OCH2Ar), 6.42 (s, 4H, ArH), 7.10 (s, 4H, ArH), 7.35–7.43
the primary ion, were varied in the range of 3.00ꢂ10ꢀ7 to
3.00ꢂ10ꢀ2 M. For a given solvent polymeric membrane electrode,
the selectivity was determined twice for each of two independently
prepared membranes. The average value for the potentiometric
selectivity was calculated from the values obtained for the four
measurements. The standard deviation of the log KPot values from
the average was 0.05 or less.
(m, 10H, ArH). 13C NMR:
d 31.1, 31.2, 31.2, 31.7, 32.0, 33.6, 34.1, 70.5,
70.6, 73.7, 78.2, 124.5, 125.5, 128.2, 128.6, 129.7, 131.9, 135.5, 137.5,
144.4, 145.2, 151.8, 153.9. Anal. calcd for C68H86O6S2: C, 76.79; H,
8.15; S, 6.03%. Found: C, 76.49; H, 7.86; S, 5.65%.
Acknowledgements
3.2.13. Cone 25,27-bis(benzyloxy)-26,28-calix[4]arene-crown-6
(12). To a stirred solution of calix[4]arene-crown-627 (1.00 g,
1.60 mmol) in THF (27 mL) and DMF (3 mL) under nitrogen, NaH
(0.19 g, 7.92 mmol) was added and the mixture was stirred at room
temperature for 15 min. Benzyl bromide (1.10 g 6.40 mmol) was
added in one portion and stirring at room temperature was con-
tinued for 24 h. After careful addition of 10% aq HCl to quench the
excess NaH, the mixture was evaporated in vacuo. The residue was
dissolved in CH2Cl2 and the solution was washed with water
(2ꢂ50 mL), dried over MgSO4 and evaporated in vacuo. The residue
was chromatographed on silica gel with CH2Cl2–MeOH (100:1)as
eluent to give 0.80 g (62%) of 12 as a white solid with mp¼153–
This research was supported by Grant D-0775 from The Welch
Foundation.
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Bo¨hmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer Academic: Dordrecht, The
Netherlands, 2001; pp 356–384.
155 ꢁC. 1H NMR:
d
3.10 (d, J¼14.0 Hz, 4H, ArCH2Ar), 3.34 (t, J¼5.0 Hz,
4H, OCH2CH2O), 3.54 (t, J¼5.0 Hz, 4H, OCH2CH2O), 3.59 (s, 4H,
OCH2CH2O), 3.76 (t, J¼8.0 Hz, 4H, OCH2CH2O), 4.16 (t, J¼8.0 Hz, 4H,
OCH2CH2O), 4.39 (d, J¼14.0 Hz, 4H, ArCH2Ar), 4.75 (s, 4H, OCH2Ar),
6.09 (d, J¼8.0 Hz, 4H, ArH), 6.24 (t, J¼8.0 Hz, 2H, ArH), 6.92, (t,
J¼8.0 Hz, 2H, ArH), 7.10 (d, J¼8.0 Hz, 4H, ArH), 7.30–7.40 (m, 6H,
ArH), 7.48 (d, J¼7.0 Hz, 4H, ArH).13C NMR:
d 30.9, 69.4, 70.5, 70.6,
70.9, 72.4, 77.5, 122.1, 122.5, 127.4, 128.0, 128.5, 129.0, 129.1, 133.2,
136.6, 137.5, 154.4, 158.1. Anal. calcd for C52H54O8: C, 77.39; H, 6.74%.
Found: C, 77.65; H, 6.44.
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