Intramolecular cyclization strategy: Synthesis of 1,3- and 1,2-calix[4]crown-7 and calix[4]crown-9 cone conformers

Article abstract of DOI:10.1007/s10847-010-9802-8

1,3- and 1,2-calix[4]crown-7 and calix[4]crown-9 cone conformers were synthesized in acceptable yields by sequential introduction of two distal or proximal polyethylene glycolic chains with terminal hydroxyls at the lower rim, monotosylation, and intramol

Full text of DOI:10.1007/s10847-010-9802-8

J Incl Phenom Macrocycl Chem (2010) 68:423–429
DOI 10.1007/s10847-010-9802-8
ORIGINAL ARTICLE
Intramolecular cyclization strategy: synthesis
of 1,3- and 1,2-calix[4]crown-7 and calix[4]crown-9
cone conformers
•
Yu-Xiang Xia Hao-Hui Zhou Yue Yin
•
•
•
Nan Qiu Jun Luo Guang-Ya Xiang
•
Received: 26 March 2010 / Accepted: 4 May 2010 / Published online: 20 May 2010
Ó Springer Science+Business Media B.V. 2010
Abstract 1,3- and 1,2-calix[4]crown-7 and calix[4]-
crown-9 cone conformers were synthesized in acceptable
yields by sequential introduction of two distal or proximal
polyethylene glycolic chains with terminal hydroxyls at the
lower rim, monotosylation, and intramolecular ring closure
reaction. According to the two-phase extraction experi-
ment, the title compounds showed mediocre affinity for
alkali and alkaline earth metal picrates. The 1,2-calix[4]-
crown-9 extracted Sr2? selectively among other alkaline
earth metal cations.
moiety, and the coordination-assisting groups deployed
around the crown ether moiety [1–3]. Apart from serving as
macrocyclic ionophores for ion recognition, nowadays the
utilization of calix[4]crowns containing large crown ether
loops has been expanded to the construction of calix-based
rotaxanes [4] and catenanes [5], which have potential
application in molecular devices.
Regarding the synthesis of calix[4]crowns, intramolec-
ular cyclization strategy has been widely applied. In this
context, the most popular method features the direct con-
densation of calix[4]arenes and oligoethylene glycol di-
tosylates in the presence of appropriate base and solvent
via nucleophilic substitution reaction. A newly developed
alternative opened a new perspective for the synthesis of
calix[4]crown by the reaction of calix[4]arenes with oli-
goethylene glycols under the Mitsunobu protocol using the
diethyl azodicarboxylate (DEAD)/triphenylphosphine
(TPP) system [6, 7]. Generally, the intermolecular cycli-
zation strategy worked well in the case of 1,3- and 1,2-
calix[4]crowns containing 3–6 ethereal oxygen atoms.
However, in some cases, where the syntheses of a 1,3-
calix[4]crown-7 analogue [8], 1,3-calix[4]crown-9 and
crown-11 analogues utilized as donor rings to assemble
calix[4]arene[2]catenanes [9], and 1,2-calix[4]monocrown-
7 [10] were involved, the yields proved to be rather poor,
presumably due to the disfavor of entropy or/and the lack
of efficient metal template effect during the ring closure
process.
Keywords Calix[4]crown-7 ꢀ Calix[4]crown-9 ꢀ
Intramolecular cyclization strategy ꢀ Synthesis ꢀ
Monotosylation
Introduction
Calix[4]crowns represent a wide range of peculiar synthetic
ionophores which possess both versatile calix[4]arene
skeletons and crown ether moieties. Intense investigation
has revealed that specific calix[4]crowns exhibit efficient
and selective binding ability towards alkali metal, alkaline
earth metal and ammonium cations, depending on the
conformation of the calix skeleton, the size of the crown
ether loop, the identity of donor atoms on the crown ether
Y.-X. Xia ꢀ Y. Yin ꢀ N. Qiu ꢀ J. Luo (&) ꢀ G.-Y. Xiang
Tongji School of Pharmacy, Huazhong University of Science
and Technology, Wuhan 430030, China
Intramolecular cyclization strategy has been less applied
in this regard and rarely seen in calixarene chemistry. The
first example of a calix[4]arene bridged at the 1,3-position
of the upper rim with a very short CH2OCH2 group was
derived from an intramolecular cyclization process by
chance rather than by design [11]. Recently, ring-closing
metathesis (RCM) reaction as an efficient approach to
e-mail: lawdream1975@163.com
H.-H. Zhou
Institute of Materia Medica, Chinese Academy of Medical
Sciences and Peking Union Medical College, Beijing 100050,
China
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J Incl Phenom Macrocycl Chem (2010) 68:423–429
macrocyclic systems via intramolecular formation of car-
bon–carbon double bonds has also been used for the syn-
thesis of novel calix[4]crowns [12]. In fact, by proper
design, the imaginable advantages of intramolecular
cyclization strategy may involve: (i) the readiness of ring
closure because of less entropy disfavor and the less
dependence on the template effect; (ii) the easy availability
of the reagents for the synthesis of calixcrowns containing
large size crown ether moieties, where the preparation of
long polyethylene glycols or corresponding ditosylates as
the ring formation segments is avoided. Based on our
preliminary work [13], herein we report a general method
for the synthesis of distally- and proximally-substituted
calix[4]crown cone conformers by an intramolecular
cyclization strategy via simple nucleophilic substitution
reaction. In view of the scarcity of the reports on the
properties of calix[4]crowns containing more than 6 oxy-
gen atoms in the crown ether units, their binding properties
towards alkali and alkaline earth metal picrates have also
been evaluated by two-phase extraction experiment.
in the presence of NaH in THF afforded corresponding
tetra-O-alkylated derivatives, followed by the removal of
the THP protecting groups with TsOHꢀH2O to give diol
compounds 2. As such, two oligoethylene glycolic chains
with terminal hydroxyls were introduced into the calix[4]-
arene skeleton at the lower rim. Efficient monotosylation of
diol compounds 2 is a guarantee of the feasibility of the
´
whole scheme. In 2002, Bouzide and Sauve reported the
Ag2O mediated highly selective monotosylation of sym-
metrical diols, the high selectivity being explained on the
basis of the difference in acidity between the two hydroxyl
groups which undergo an intramolecular hydrogen bonding
[14]. Application of this synthetic protocol to substrates 2a
and 2b, which contain two hydroxyl groups at the lower
rim, led to the formation of 3a and 3b, respectively, in good
yields. Subsequent intramolecular cyclization was smoothly
achieved in the presence of NaH in THF to furnish 1,3-
calix[4]crown-7 4a and calix[4]crown-9 4b.
The successful synthesis of the 1,3-calix[4]crown-7 and
calix[4]crown-9 derivatives prompted us to synthesize their
1,2-calix[4]crown counterparts for the purposes of (i)
investigating the generality of this four-step sequence for
the synthesis of calixcrowns with large crown ether loops
and (ii) providing more examples for the less studied 1,2-
calix[4]crowns [15–18]. Thus, 25,26-dipropoxy-27,28-
dihydroxy-p-tert-butylcalix[4]arene 5 as the starting mate-
rial was subjected to the same procedure aforementioned
and the key steps of monotosylation and intramolecular ring
closure worked well under similar conditions to afford 1,2-
Results and discussion
We initially synthesized the 1,3-calix[4]crown-7 and
calix[4]crown-9 cone conformers by a four-step sequence as
depicted in Scheme 1. The treatment of 25,27-dipropoxy-
26,28-dihydroxy-p-tert-butylcalix[4]arene 1 with readily
available THP-protected oligoethylene glycol monotosylates
Scheme 1 Synthesis of 1,3-
calix[4]crown-7 cone conformer
4a, 1,3-calix[4]crown-9 cone
conformer 4b, 1,2-
calix[4]crown-7 cone conformer
4c and 1,2-calix[4]crown-9 cone
conformer 4d
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J Incl Phenom Macrocycl Chem (2010) 68:423–429
425
calix[4]crown-7 4c and 1,2-calix[4]crown-9 4d in good
yields. It is worth noting that monotosylation of 1,2-dipro-
pyl diol compounds 2c and 2d afforded 3c and 3d,
respectively, as inherently chiral calix[4]arenes of AABC
substitution pattern at the lower rim.
31.0 ppm. By comparison, the resonances of its aromatic
protons and tert-butyl protons centered at 6.77 ppm and
1.07 ppm, indicating a regular cone conformation (Fig. 1).
The complexation ability of 4a–d towards alkali and
alkaline earth metal ions was evaluated by liquid–liquid
extraction experiment. According to the results (Table 1),
1,3-dipropyl calix[4]crown-7 (4a) extracted all the alkali
metal cations with mediocre efficiency and selectivity, the
highest extraction percentage occurring in the case of Na?
(7.5%). Similarly, its crown-9 counterpart (4b) and
1,2-counterpart (4c) showed mediocre efficiency and
selectivity towards alkali metal cations, with the highest
extraction percentage of 7.2% for K? and 8.9% for Na?,
respectively. Comparatively, 1,2-dipropyl calix[4]crown-9
(4d) had the lowest affinity towards alkali metal cations,
the highest extraction percentage occurring in the case of
Cs? (3.1%). Generally, 4a–d extracted alkaline earth metal
cations less efficiently than alkali metal cations. Com-
The structures of all new compounds were fully con-
firmed by NMR, ESI-MS and HRMS data. 1,3-calix[4]-
crowns and their 1,2-counterparts showed obvious
structural differences, which was reflected from the NMR
spectra of typical compounds 4b and 4d. For 4b, the two
singlets attributable to the aromatic protons, a pair of
doublets assignable to the ArCH2Ar methylene bridge
protons (in a ratio of 1:1) and the two singlets attributable
to the tert-butyl groups are in agreement with its molecular
symmetry. For 4d, which has only one plane of symmetry,
three pairs of doublets are assignable to the ArCH2Ar
methylene bridge protons (in a ratio of 1:1:2, partially
overlapped). In view of the differences of the chemical
shift values of the aromatic protons (6.97 ppm and
6.57 ppm) as well as that of the tert-butyl protons
(1.23 ppm and 0.91 ppm), combining with the signals
arising from the ArCH2Ar methylene bridge carbons at
around 30.9 ppm, 1,3-calix[4]crown 4b was believed to
adopt a pinched cone conformation. 1,2-Calix[4]crown 4d
also adopts a cone conformaiton, which could be deduced
from the ArCH2Ar methylene bridge carbons appearing at
pounds 4b and 4c didn’t extract Mg2?, Ba2? and Mg2?
,
Ca2?, respectively. Compound 4d proved to be most
selective for Sr2? because no extraction was detected for
all other alkaline earth metal cations.
Though the title compounds did not show pronounced
extraction efficiency and selectivity towards alkali metal
and alkaline earth metal cations, it is conceivable that by
replacing the lower rim propyl groups with coordinating
t-Bu
t-Bu
~
4b
~
H2O
O
O
O
O
O O
O
O
ArH
ArH
O O
O
ArCH2Ar
ArCH2Ar
3.0
7.0
6.0
5.0
4.0
2.0
1.0
0.0
ppm
t-Bu
4d
~
O
O
O
O
O
O
O
O
O
O
ArH
ArCH2Ar
O
ArCH2Ar
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
ppm
Fig. 1 1H NMR spectra of 4b and 4d (400 MHz, CDCl3, 25 °C)
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J Incl Phenom Macrocycl Chem (2010) 68:423–429
was stirred at room temperature in the presence of NaH
(487 mg, 8.0 equiv) for 30 min, followed by addition of a
solution of 1-tosyl-10-(tetrahydro pyran-2-yl)-1,4,7,10-tet-
raoxadecane or 1-tosyl-13-(tetrahydro pyran-2-yl)-1,4,
7,10,13-penta oxatridecane (3.0 equiv) in THF (30 mL).
The reaction mixture was refluxed under N2 for 3d.
Methanol was added dropwise to quench the reaction
(caution!). After evaporation of the solvent under reduced
pressure, the residue was partitioned between water
(50 mL) and CH2Cl2 (2 9 50 mL). The combined organic
layer was dried over Na2SO4. Subsequent purification by
column chromatography (SiO2, petroleum ether/acetone
4:1) gave corresponding tetra-O-alkylated intermediates,
which was further treated with TsOHꢀH2O (1.0 equiv) in
95% ethanol (50 mL) under reflux for 3 h. Aqueous NaOH
(1 N, 3 mL) was added to quench the reaction. After
evaporation of the solvent under reduced pressure, the
residue was partitioned between aqueous HCl (1 N,
50 mL) and CH2Cl2 (2 9 50 mL). The combined organic
layer was dried over Na2SO4. Subsequent purification by
column chromatography furnished compounds 2c or 2d as
a colorless solid.
Table 1 Extraction percentage of alkali metal and alkaline earth
metal picrates by 4a–d, from water to dichloromethane, at 16 2 °C
c4aalix[4] Li? Na? K? Rb? Cs? Mg2? Ca2? Sr2? Ba2?
crowns
4a
4b
4c
4d
4.2 7.5 2.2 1.5 4.1 1.6
3.9
2.8
0
6.1 4.0
2.7
1.4 2.1
5.0
6.1 6.3 7.2 2.4 2.4
3.1 8.9 4.1 4.0 2.8
0
0
0
0
1.7 1.4 1.5
0
3.1
0
0
groups such as ester groups, amide groups and proton-
ionizable groups [15, 16], the binding efficiency and
selectivity should be enhanced.
Conclusion
We have offered a general approach to 1,3- and 1,2-
calix[4]crown-7 and calix[4]crown-9 cone conformers by
an intramolecular cyclization strategy in acceptable yields,
which may complement the traditional intermolecular
cyclization strategy for the synthesis of calixcrowns,
especially that of large crown ether loops. The 1,3-
calix[4]crowns in question adopt the pinched cone con-
formation and the 1,2-counterparts adpot the regular cone
conformaiton according to NMR data analysis. Currently,
we are engaged in exploring the possibility of applying our
method to the design and synthesis of topologically inter-
esting calixcrowns which could not be prepared otherwise.
Compound 2c: Column chromatography (SiO2, petro-
leum ether/acetone 3:1). Yield 76%. Mp 62–64 °C. 1H
NMR (CDCl3, 400 MHz) d 6.79–6.76 (m, 8H, ArH), 4.46
(d, 1H, J = 12.8 Hz, ArCH2Ar), 4.42 (d, 1H, J = 12.8 Hz,
ArCH2Ar), 4.38 (d, 2H, J = 12.8 Hz, ArCH2Ar), 4.11–
3.94 (m, 8H, OCH2CH2O), 3.85–3.81 (m, 4H, ArOCH2
CH2CH3), 3.75–3.70 (m, 12H, OCH2CH2O), 3.61–3.59 (m,
4H, OCH2CH2O), 3.43 (t, 2H, J = 6.4 Hz, OH), 3.11 (d,
3H, J = 12.4 Hz, ArCH2Ar), 3.10 (d, 1H, J = 12.4 Hz,
ArCH2Ar), 2.06–1.96 (m, 4H, ArOCH2CH2CH3), 1.08 (s,
18H, C(CH3)3), 1.07 (s, 18H, C(CH3)3), 1.00 (t, 6H, J =
7.6 Hz, ArOCH2CH2CH3). 13C NMR (CDCl3, 100 MHz) d
153.5, 153.2, 144.6, 144.3, 133.83, 133.76, 133.7, 125.0,
124.9, 77.2, 72.8, 72.6, 70.5, 70.43, 70.40, 61.7, 33.82,
33.79, 31.43, 31.41, 31.01, 30.96, 23.3, 10.4. ESI-MS m/z
1019.6 [M ? Na?], 1035.6 [M ? K?]. HRMS calcd for
C62H92O10Na [M ? Na?] 1019.6588; found 1019.6591.
Compound 2d: Column chromatography (SiO2, petro-
leum ether/acetone 3:1). Yield 72%. Mp 66–70 °C. 1H
NMR (CDCl3, 400 MHz) d 6.77–6.76 (m, 8H, ArH), 4.43
(d, 1H, J = 12.2 Hz, ArCH2Ar), 4.41 (d, 1H, J = 12.4 Hz,
ArCH2Ar), 4.39 (d, 2H, J = 12.3 Hz, ArCH2Ar), 4.14–
3.94 (m, 8H, OCH2CH2O), 3.82 (t, 4H, J = 7.8 Hz,
ArOCH2CH2CH3), 3.72–3.57 (m, 24H, OCH2CH2O),
3.113 (d, 1H, J = 12.5 Hz, ArCH2Ar), 3.106 (d, 2H,
J = 12.6 Hz, ArCH2Ar), 3.10 (d, 1H, J = 12.7 Hz,
ArCH2Ar), 2.97 (s, 2H, OH), 2.01 (sextet, 4H, J = 7.8 Hz,
ArOCH2CH2CH3), 1.075 (s, 18H, C(CH3)3), 1.067 (s, 18H,
Experimental
Melting points were measured on a Beijing Taike X-5
apparatus and uncorrected. NMR spectra were recorded on a
Bruker Av-400 spectrometer with CDCl3 as a solvent and
TMS as an internal standard. ESI-MS spectra were recorded
on an LCQ Deca XP mass spectrometer. High resolution
mass spectra were recorded on a Waters Q-Tof micro mass
spectrometer. UV–Vis spectra were recorded by an SP-
756PC UV–Vis spectrophotometer. Compounds 1 [19], 2a
[20], 5 [21], 1-tosyl-10-(tetrahydropyran-2-yl)-1,4,7,10-tet-
raoxadecane, 1-tosyl-13-(tetrahydro pyran-2-yl)-1,4,7,10,13-
penta oxatridecane [22] and Ag2O [23] were prepared as
described in pertinent literatures. THF was freshly distilled
from Na-benzophenone prior to use. The syntheses of 2b, 3b
and 4b have been reported by us previously [13].
General procedure for the syntheses of diol compounds
2c and 2d
C(CH3)3), 1.00 (t, 6H, J = 7.8 Hz, ArOCH2CH2CH3). 13
C
A solution of 25,26-dipropoxy-27,28-dihydroxy-p-tert-
butylcalix[4]arene 5 (1.86 g, 2.54 mmol) in THF (40 mL)
NMR (CDCl3, 100 MHz) d 153.6, 153.3, 144.6, 144.3,
133.8, 133.7, 124.94, 124.89, 72.8, 72. 7, 70.7, 70.6, 70.5,
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J Incl Phenom Macrocycl Chem (2010) 68:423–429
427
70.41, 70.38, 61.7, 33.82, 33.80, 31.5, 31.4, 31.1, 31.0,
23.3, 10.4. ESI-MS m/z 1107.8 [M ? Na?]. HRMS calcd
for C66H100O12Na [M ? Na?] 1107.7112; found
1107.7106.
31.42, 31.40, 31.04, 30.98, 23.32, 23.28, 21.62, 10.40,
10.36. ESI-MS m/z 1173.7 [M ? Na?]. HRMS calcd for
C69H98O12SNa [M ? Na?] 1173.6677; found 1173.6672.
Compound 3d: Column chromatography (SiO2, petro-
leum ether/acetone 5:1). Yield 76%. Mp 81–83 °C. 1H
NMR (CDCl3, 400 MHz) d 7.79 (d, 2H, J = 8.2 Hz,
SO2ArH), 7.33 (d, 2H, J = 8.2 Hz, SO2ArH), 6.77 (s, 8H,
ArH), 4.41 (d, 1H, J = 12.4 Hz, ArCH2Ar), 4.40 (d, 3H,
J = 12.5 Hz, ArCH2Ar), 4.16–3.93 (m, 10H, OCH2-
CH2O), 3.81 (t, 4H, J = 7.4 Hz, ArOCH2CH2CH3), 3.70–
3.56 (m, 22H, OCH2CH2O), 3.11 (d, 1H, J = 12.4 Hz,
ArCH2Ar), 3.104 (d, 1H, J = 12.6 Hz, ArCH2Ar), 3.097
(d, 2H, J = 12.6 Hz, ArCH2Ar), 2.63 (s, 1H, OH), 2.44 (s,
3H, SO2ArCH3), 2.01 (sextet, 4H, J = 7.4 Hz,
ArOCH2CH2CH3), 1.08 (s, 9H, C(CH3)3), 1.07 (s, 18H,
C(CH3)3), 1.06 (s, 9H, C(CH3)3), 0.99 (t, 3H, J = 7.4 Hz,
ArOCH2CH2CH3), 0.98 (t, 3H, J = 7.4 Hz, ArOCH2CH2
CH3). 13C NMR (CDCl3, 100 MHz) d 153.6, 153.5,
153.32, 153.30, 144.8, 144.5, 144.3, 133.83, 133.79,
133.77, 133.75, 133.70, 133.0 129.8, 128.0, 124.93,
124.89, 77.2, 72.8, 72.7, 72.5, 70.8, 70.7, 70.63, 70.58,
70.44, 70.39, 70.37, 69.2, 68.7, 61.8, 33.81, 33.80, 31.45,
31.43, 31.1, 31.0, 23.3, 21.6, 10.4. ESI-MS m/z 1261.8
[M ? Na?]. HRMS calcd for C73H106O14SNa [M ? Na?]
1261.7201; found 1261.7203.
General procedure for the monotosylation of 2 to afford
3a–d
To a solution of 2 (0.37 mmol) in CH2Cl2 (40 mL) were
added Ag2O (128 mg, 1.5 equiv), KI (12 mg, 0.2 equiv)
and TsCl (84 mg, 1.2 equiv). The reaction mixture was
stirred overnight at room temperature. After filtration and
evaporation of the solvent under reduced pressure, the
residue was directly subjected to column chromatography
to give 3 as colorless solids.
Compound 3a: Column chromatography (SiO2, petro-
leum ether/acetone 5:1). Yield 60%. Mp 92–95 °C. 1H
NMR (CDCl3, 400 MHz) d 7.79 (d, 2H, J = 8.3 Hz,
SO2ArH), 7.32 (d, 2H, J = 8.3 Hz, SO2ArH), 6.85 (d, 2H,
ArH), 6.84 (d, 2H, ArH), 6.69 (d, 4H, ArH), 4.382 (d, 2H,
J = 12.5 Hz, ArCH2Ar), 4.378 (d, 2H, J = 12.5 Hz,
ArCH2Ar), 4.16–3.60 (m, 24H, OCH2CH2O), 3.78 (t, 4H,
J = 7.6 Hz, ArOCH2CH2CH3), 3.12 (d, 2H, J = 12.5 Hz,
ArCH2Ar), 3.11 (d, 2H, J = 12.5 Hz, ArCH2Ar), 2.43
(s, 3H, SO2ArCH3), 2.00 (sextet, 4H, J = 7.6 Hz, ArOCH2
CH2CH3), 1.145 (s, 9H, C(CH3)3), 1.133 (s, 9H, C(CH3)3),
1.01 (s, 18H, C(CH3)3), 0.99 (t, 6H, J = 7.6 Hz, ArOCH2
CH2CH3). 13C NMR (CDCl3, 100 MHz) d 153.50, 153.48,
153.3, 144.8, 144.71, 144.67, 144.2, 134.2, 133.2, 133.0,
129.8, 128.0, 125.0, 124.8, 77.2, 72.6, 72.44, 72.35, 70.8,
70.6, 70.47, 70.46, 70.3, 69.2, 68.8, 61.8, 33.9, 33.7, 31.5,
31.4, 31.0, 23.4, 21.6, 10.5. ESI-MS m/z 1173.8 [M ?
Na?]. HRMS calcd for C69H98O12SNa [M ? Na?]
1173.6677; found 1173.6680.
General procedure for intramolecular ring closure
to afford 4a–d
A solution of 3 (0.16 mmol) in THF (55 mL) was
refluxed in the presence of NaH (45 mg, 12.0 equiv)
under N2 for 1d. Methanol was added dropwise to quench
the reaction (caution!). After evaporation of the solvent
under reduced pressure, the residue was partitioned
between water (50 mL) and CH2Cl2 (2 9 50 mL). The
combined organic layer was dried over Na2SO4. Sub-
sequent purification by column chromatography gave 4 as
colorless solids.
Compound 3c: Column chromatography (SiO2, petro-
leum ether/acetone 4:1). Yield 75%. Mp 89–90 °C. 1H
NMR (CDCl3, 400 MHz) d 7.79 (d, 2H, J = 8.0 Hz,
SO2ArH), 7.32 (d, 2H, J = 8.0 Hz, SO2ArH), 6.79–6.75
(m, 8H, ArH), 4.41 (d, 1H, J = 12.4 Hz, ArCH2Ar), 4.40
(d, 1H, J = 12.4 Hz, ArCH2Ar), 4.39 (d, 2H, J = 12.4 Hz,
ArCH2Ar), 4.16–3.93 (m, 10H, OCH2CH2O), 3.81 (t, 4H,
J = 7.6 Hz, ArOCH2CH2CH3), 3.70–3.59 (m, 14H,
OCH2CH2O), 3.11 (d, 2H, J = 12.4 Hz, ArCH2Ar), 3.10
(d, 2H, J = 12.4 Hz, ArCH2Ar), 2.58 (s, 1H, OH), 2.43 (s,
3H, SO2ArCH3), 2.00 (sextet, 4H, J = 7.6 Hz,
ArOCH2CH2CH3), 1.09 (s, 9H, C(CH3)3), 1.08 (s, 9H,
C(CH3)3), 1.06 (s, 18H, C(CH3)3), 0.99 (t, 3H, J = 7.6 Hz,
ArOCH2CH2CH3), 0.98 (t, 3H, J = 7.6 Hz, ArOCH2
CH2CH3). 13C NMR (CDCl3, 100 MHz) d 153.6, 153.5,
153.3, 153.2, 144.8, 144.63, 144.56, 144.30, 144.27, 133.9,
133.78, 133.75, 133.7, 133.6, 133.0, 129.8, 128.0, 125.0,
124.92, 124.85, 72.7, 72.61, 72.56, 70.8, 70.52, 70.49,
70.41, 70.37, 69.2, 68.8, 61.8, 33.82, 33.79, 33.77, 31.44,
Compound 4a: Column chromatography (SiO2, petro-
1
leum ether/acetone 2:1). Yield 74%. Mp 214–216 °C. H
NMR (CDCl3, 400 MHz) d 7.09 (s, 4H, ArH), 6.45 (s, 4H,
ArH), 4.36 (d, 4H, J = 12.5 Hz, ArCH2Ar), 4.26–4.14 (m,
8H, OCH2CH2O), 3.77 (s, 8H, OCH2CH2O), 3.71 (s, 8H,
OCH2CH2O), 3.68 (t, 4H, J = 7.4 Hz, ArOCH2CH2CH3),
3.12 (d, 4H, J = 12.5 Hz, ArCH2Ar), 1.96 (sextet, 4H,
J = 7.4 Hz, ArOCH2CH2CH3), 1.32 (s, 18H, C(CH3)3),
1.04 (t, 6H, J = 7.4 Hz, ArOCH2CH2CH3), 0.82 (18H,
C(CH3)3). 13C NMR (CDCl3, 100 MHz) d 154.4, 152.4,
145.0, 144.0, 135.5, 131. 9, 125.4, 124.5, 77.7, 72.0, 71.2,
70.7, 70.5, 70.4, 69.8, 34.1, 33.6, 31.7 31.1, 30.9, 23.5,
10.7. ESI-MS m/z 1001.8 [M ? Na?]. HRMS calcd for
C62H90O9Na [M ? Na?] 1001.6483; found 1001.6478.
123

428
J Incl Phenom Macrocycl Chem (2010) 68:423–429
Compound 4c: Column chromatography (SiO2, petro-
1
experiment of alkaline earth metal picrates, 4 9 10-5 M of
the calixarenes and alkaline earth metal picrates was used.
All data were obtained as the average of at least three
independent experiments.
leum ether/acetone 7:1). Yield 71%. Mp 131–134 °C. H
NMR (CDCl3, 400 MHz) d 6.78–6.77 (m, 8H, ArH), 4.50
(d, 1H, J = 12.8 Hz, ArCH2Ar), 4.42 (d, 1H, J = 12.4 Hz,
ArCH2Ar), 4.38 (d, 2H, J = 12.4 Hz, ArCH2Ar), 4.13–
3.94 (m, 8H, OCH2CH2O), 3.83 (t, 4H, J = 7.6 Hz,
ArOCH2CH2CH3), 3.75–3.68 (m, 16H, OCH2CH2O), 3.12
(d, 1H, J = 12.4 Hz, ArCH2Ar), 3.11 (d, 2H, J = 12.4 Hz,
ArCH2Ar), 3.10 (d, 1H, J = 12.8 Hz, ArCH2Ar), 2.02
(sextet, 4H, J = 7.6 Hz, ArOCH2CH2CH3), 1.08 (s, 18H,
C(CH3)3), 1.07 (s, 18H, C(CH3)3), 1.00 (t, 6H, J = 7.6 Hz,
ArOCH2CH2CH3). 13C NMR (CDCl3, 100 MHz) d 153.6,
153.3, 144.5, 144.2, 133.9, 133.8, 133.7, 125.0, 124.89,
124.87, 77.2, 73.0, 70.73, 70.68, 70.6, 70.4, 33.81, 33.78,
31.44, 31.43, 31.0, 30.9, 23.3, 10.4. ESI-MS m/z 1001.7
[M ? Na?]. HRMS calcd for C62H90O9Na [M ? Na?]
1001.6483; found 1001.6487.
Acknowledgments The authors are grateful to Project Aurora
´
(ChenGua¯ng) of Wuhan Science and Technology Bureau for Young
Scholars (No. 200750731267) and National Natural Science Foun-
dation of China (No. 20902029) for financial support.
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