Synthesis of calix[4]crowns containing soft and hard ion binding sites via click chemistry

Article abstract of DOI:10.1039/b816467c

A series of triazole-modified calix[4]crowns, 3, containing hard and soft ion binding sites were synthesized in good yields via click chemistry. The hard and soft ion binding sites may selectively complex alkali metal or transition metal cations. Compound 3a shows good complex selectivity towards Pb ²⁺ and 3c shows the highest Li⁺/K⁺ extraction ratio, suggesting that the triazole groups play an important role in metal ion binding.

Full text of DOI:10.1039/b816467c

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LETTER
www.rsc.org/njc | New Journal of Chemistry
Synthesis of calix[4]crowns containing soft and hard ion binding sites
via click chemistryw
Junyan Zhan, Demei Tian and Haibing Li*
Received (in Durham, UK) 19th September 2008, Accepted 13th November 2008
First published as an Advance Article on the web 24th November 2008
DOI: 10.1039/b816467c
A series of triazole-modified calix[4]crowns, 3, containing hard
and soft ion binding sites were synthesized in good yields via
click chemistry. The hard and soft ion binding sites may
selectively complex alkali metal or transition metal cations.
Under our selected conditions, a series of calix[4]crowns were
synthesized via click chemistry, as shown in Scheme 1. At first, a
series of azide-type bridging reagents were readily synthesized in
high yields and without further purification by reacting
oligoethylene glycol ditosylates and 1,2-bistosyloxyethoxybenzene
2
+
Compound 3a shows good complex selectivity towards Pb
+
+
10
and 3c shows the highest Li /K extraction ratio, suggesting
that the triazole groups play an important role in metal ion
binding.
with NaN3 in DMSO at 50 1C. Then, the reactions of
1
1
alkynylcalixarene, 1, with 2a, 2b and 2c (n = 1, 2, 3) were
carried out in DMF at 90 1C with copper(II) sulfate and
sodium ascorbate to afford triazole-modified calix[4]crown-3,
3a, calix[4]crown-4, 3b, and calix[4]crown-5, 3c, in yields of 81,
With the aim of advancing the ability of multiple recognition
and the mutual effects of binding subunit occupation,
considerable attention has been focused on polytoptic systems
combining two or more binding sites within the same
9
62 and 68%, respectively. However, with 2d as the bridging
reagent, complicated mixtures were obtained.
After much effort with the more polar mixed solvents
1
2
3
architecture. Calixcrowns comprise a family of calixarenes
THF/H
obtained in 89% yield by recrystallization. 3b and 3c were
2
O, triazole-modified calix[4]benzocrown-4, 3d, was
8
that exhibit a superior recognition ability towards metal
cations by the cooperation of calixarene and crown moieties.
Until now, to the best of our knowledge, only three cases
concerning calixcrown-based polytoptic systems were known.
In 1997, Vicens et al. synthesized calix[4]-triaza-oxa-benzo-
also synthesized with the THF/H
yield was observed.
The structures of these compounds were characterized by
O system, but no improved
2
1
13
EI(+)MS spectra, elemental analyses, and H and C NMR
studies. The EI(+)MS spectra of 3a, 3b, 3c and 3d show
the expected molecular ion peaks, which indicate that the
calix[4]arene moiety is intramolecularly-bridged by the crown
4
crown-6, containing hard and soft ion binding sites. Chen
et al. subsequently reported a C -symmetrical p-tert-calix[6]-
s
1
binding sites. Most recently, we reported calix[4]diazacrown-4
,4-crown-4-2,6-dioxo-diaza crown-4 with hard and soft ion
5
1
unit via the triazole groups. In the H NMR spectra of the
6
oligomers containing hard and soft ion binding sites.
synthesized calix[4]crowns, two signals for the aromatic
protons, two doublets for the bridging methylene groups and
two singlets for the tert-butyl groups suggest that all of the
compounds are in a cone conformation. For compound 3a
and 3d, the cone conformation was also corroborated by
the presence of two peaks for the methylene resonances in
In calixarene chemistry, intramolecular bridging is generally
much more difficult to achieve due to the quite complicated
2
products and their low yields. Whereas in click chemistry,
click reactions are modular, tolerant of a wide range of
solvents and functional groups, simple to perform, and
7
very high yielding. Click reactions have already been used
13
12
the C NMR spectrum. Furthermore, the structure of
8
9
successfully to prepare water soluble and hybrid calixarenes.
Therefore, we wanted to employ a new synthetic strategy to
bridge intramolecularly calixarenes via click chemistry.
Furthermore, the triazole groups and the crown ether unit,
as soft and hard ion binding sites, were introduced to the
calixarene cavity by a one-step pathway. In this Letter, with
our continued interest in calixcrown-based polytoptic systems,
we wish to report the synthesis of a calix[4]crown containing
hard and soft ion binding sites via click chemistry in good
yields, and also its extraction ability towards different metal
cations by its hard and soft ion binding sites.
Key Laboratory of Pesticide and Chemical Biology (CCNU),
Ministry of Education, College of Chemistry, Central China Normal
University, Wuhan 430079, PR China.
E-mail: lhbing@mail.ccnu.edu.cn; Tel: +86 27-67866423
w CCDC 701086. For crystallographic data in CIF or other electronic
format see DOI: 10.1039/b816467c
Scheme 1
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Fig. 1 The X-ray crystal structure of compound 3a.
Fig. 2 The extraction capacity of calix[4]crowns 3a, 3b, 3c and 3d
towards transition metal cations.
compound 3a was further confirmed by an X-ray crystallo-
graphic analysis.w
Calix[4]crown derivative 3a adopts a cone conformation
transition metal cations are displayed in Fig. 2. From the data
given in Fig. 2, triazole-modified calix[4]crowns show good
extraction abilities towards transition metal cations. This
could be attributed to the nitrogen atom-containing 1,2,3-
triazole groups, which are preferable for complexing the more
polarizable transition metal cations. The phenomenon might
also reflect the ‘‘principle of hard and soft acids and bases’’
1
3
(
Fig. 1); the connecting methylene carbon atoms forming an
approximate plane. The interplanar angles between this
plane and the rings carrying the crown are 73.47 and 68.981,
while these angles are 44.10 and 50.171 for those carrying the
OH groups. Thus, the presence of a crown attached to the
phenyl rings of the calix[4]arene pushes them away. The two
opposite arenes bearing the crown have an interplanar angle of
1
5
introduced by Ho. Meanwhile, triazole-modified calix[4]-
2
+
crown-3 3a exhibited a high affinity towards Pb
ions.
can be bound via the
coordination of two triazole groups. Therefore, the high
1
7
2+
3
7.581, and between the second pair the angle is 85.751,
According to the literature, Pb
showing that the ring pair having the crown attached to them
are pointed into the cavity while the other pair are almost
perpendicular to each other, as has been seen previously in
2
+
selectivity towards Pb
could because the two crown-3-
2
+
linked triazole groups facilitate strong Pb ion binding.
It can be seen from Table 1 that host 3a showed the higher
extraction abilities towards alkali metal cations. It is tempting
to explain the higher percentage extractability of 3a by a change
in the 1,3-alternate conformation facilitated by the short crown
1
4
substituted p-tert butylcalix[4]arenes. The torsion angles
C(51)–C(50)–O(5)–C(49) and C(48)–C(49)–O(5)–C(50) are
1
10.8 and 112.91, respectively. The two triazole groups have
an interplanar angle of 65.521. Because the single-crystal
diffraction measurement of the crystal was carried out at a
lower temperature (200 K), there are CH Cl and water
1
chain, but H NMR studies gave no indication of such a
2
2
conformational change. In comparison with 4, triazole-
modified p-tert-butylcalix[4]crown-5, 3c, showed a higher
molecules in the crystal’s unit cell.
+
extraction selectivity towards Li . The extraction ratio Li /K
+
+
An examination of CPK molecular models reveals that
compounds 3a, 3b, 3c and 3d are well preorganized for
the extraction of cations. The ion binding properties of
of compound 3c is up to 6.24, whereas with compound 4 it is only
up to 0.0068. It is pertinent to note that the polyether chain of 3c
is able to coil and bring about the collapse of the cavity to form a
larger pseudocircular crown unit, which can then accommodate a
larger potassium ion. However, for host 3c, the pseudocircular
crown unit was much smaller than that of compound 4 due to the
introduction of the triazole groups. Therefore, the smaller lithium
ion fitted into the cavity composed from the crown unit, empha-
sizing the importance of the size-fit effect. At the same time, it
revealed that the triazole groups inflected the extraction ability
and selectivity of the hard ion binding site, composed from the
crown unit, towards the lithium ion.
triazole-modified calix[4]crowns
extracting picrate salts from the aqueous to the organic phase.
In order to determine the influence of the 1,2,3-triazole groups
3 were investigated by
15
1
6
on the extraction, p-tert-butylcalix[4]crown-5, 4, was used as
a reference compound. The percentage extraction of hosts 3a,
3b, 3c, 3d and reference compound 4 towards alkali metal
cations is summarized in Table 1. The extraction results for
Table 1 The percentage extraction of alkali metal cations
+
Li
+
+
K
+
Cs
+
Li /K
+
Host
Na
Experimental
3
3
3
3
4
a
b
c
36.9
21.9
13.1
15.5
25.2
8.7
7.3
5.1
0.3
27.9
7.4
2.1
5.9
24.7
6.4
8.0
7.3
—
1.32
2.96
6.24
2.63
General
d
1
a
H NMR spectra were recorded on Varian Mercury VX400
0.08
11.8
o0.01
and 600 instruments at ambient temperature with TMS as the
1
internal standard. C NMR spectra were recorded on a
a
These data are quoted from ref. 16.
3
7
26 | New J. Chem., 2009, 33, 725–728
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Varian Mercury VX400 instrument at ambient temperature
with TMS as the internal standard. EI-MS were recorded
on a Finnigan LCQ-Advantage instrument. UV-vis spectra
were obtained using a Scinco S-3100 UV-Vis recording
spectrophotometer. All chemicals were A.R. grade and were
purified by standard procedures.
The CHCl
solvent removed under reduced pressure. The residue was
3
layer was dried over MgSO
4
and the
recrystallized from CH Cl /MeOH to afford 3d as a white
2
2
solid in 89% yield.
1
Compound 3d. H NMR (CDCl
3
, 400 MHz): d 0.99 (s, 18H,
), 3.30 (d, J = 13.0 Hz, 4H,
C(CH
ArCH Ar), 4.19 (d, J = 13.0 Hz, 4H, ArCH Ar), 4.49 (t, J =
3
)
3
), 1.27 (s, 18H, C(CH
3
)
3
General procedure for the synthesis of compounds 3a, 3b and 3c
2
2
4
.6 Hz, 4H, OCH
2
2
), 4.80 (t, J = 4.6 Hz, 4H, OCH ), 5.27
1
(241 mg, 0.333 mmol), CuSO
4
Á5H
2
O (50 mg, 0.201 mmol)
(
s, 4H, ArOCH ), 6.84 (s, 4H, ArH), 6.87 (s, 4H, ArH), 7.03
2
and sodium ascorbate (100 mg, 0.505 mmol) were added to a
solution of 2a (78 mg, 0.50 mmol) in DMF (10.0 mL). The
mixture was heated at 90 1C for 10 h, and then diluted with
ethyl acetate (10 mL) and washed with water (3 Â 5 mL). The
1
3
(
s, 4H, ArH), 7.42 (brs, 2H, ArOH), 8.35 (s, 2H, NCH);
C
NMR (CDCl , 100 MHz): d 30.7, 31.0 (CH ), 31.5, 31.7
3
3
(
ArCH Ar), 33.8, 33.9 (C(CH3)3), 50.4 (CH N), 68.1
2
2
(
CH
2
O), 72.9 (ArOCH
2
), 115.9, 125.2, 125.6, 125.9, 127.7,
organic phase was dried over MgSO , filtered and the
4
1
1
32.5, 145.0, 147.3, 148.3, 150.1, 150.3 (ArC), 125.0 (NCH),
+
41.8 (NC); EI(+)MS m/z = 973.0 (MH ). Anal. calc. for
solvent removed under reduced pressure. The residue was
2 2
recrystallized from CH Cl /MeOH to afford 3a as a white
C
60
H
72
6
N O
6
: C, 74.04; H, 7.46; N, 8.64; found: C, 74.01; H,
solid in 81% yield. Compounds 3b and 3c were prepared under
identical conditions. Purification by column chromatography
eluting with hexane/ethyl acetate (v/v = 2 : 1, 1 : 1) afforded 3b
and 3c as white solids in yields of 62 and 68%, respectively.
7
.42; N, 8.68%.
Solvent extraction experiments
Picrate extraction experiments were performed by following
À5
1
1
5
Compound 3a. H NMR (CDCl , 400 MHz): d 0.89 (s, 18H,
3
Ho’s procedure. 2 mL of a 5Â10
M aqueous picrate
solution and 1 mL of a 5 Â 10 M solution of calixarene in
À4
C(CH ) ), 1.30 (s, 18H, C(CH ) ), 3.34 (d, J = 13.0 Hz, 4H,
3
3
3 3
ArCH
2
Ar), 3.90 (t, J = 4.6 Hz, 4H, OCH
Ar), 4.51 (t, J = 4.8 Hz, 4H, OCH
), 6.74 (s, 4H, ArH), 6.91 (s, 2H, NCH), 7.10
2
), 4.26 (d, J = 13.0
CHCl were vigorously agitated for 5 min in a stoppered glass
3
Hz, 4H, ArCH
2
2
), 5.27
tube with a mechanical shaker, magnetically stirred in a
thermostated water bath at 25 1C for 2 h and finally left to
stand for an additional 30 min. The concentration of picrate
ions remaining in the aqueous phase was then determined by
UV spectra from the resulting absorbance at 380 nm. Blank
experiments showed that no picrate extraction occurred in the
absence of calixarene.
(
s, 4H, ArOCH
s, 4H, ArH), 8.22 (s, 2H, ArOH); C NMR (CDCl
), 31.5, 31.7 (ArCH Ar), 33.8
N), 69.2 (CH O), 71.4 (ArOCH ),
25.3, 125.6, 127.7, 132.0, 145.4, 147.5, 149.5, 150.3 (ArC),
2
1
3
(
3
, 100
MHz): d 30.7, 30.9 (CH
C(CH ), 50.4 (CH
3
2
(
3
)
3
2
2
2
1
1
+
24.9 (NCH), 142.1 (NC); EI(+)MS m/z = 882.0 (MH2 ).
Anal. calc. for C H N O : C, 73.61; H, 7.78; N, 9.54; found:
5
4
68
6
5
C, 73.56; H, 7.71; N 9.52%.
Acknowledgements
1
Compound 3b. H NMR (CDCl
3
, 600 MHz): d 0.97 (s, 18H,
), 3.29 (d, J = 12.9 Hz, 4H,
), 3.60 (s, 2H, OCH ), 3.70
), 3.95 (s, 2H, OCH ), 4.16 (d, J = 12.9 Hz,
Ar), 4.63 (s, 2H, OCH ), 5.25 (s, 4H, ArOCH ),
.81 (s, 4H, ArH), 7.04 (s, 4H, ArH), 7.02 (s, 2H, NCH), 8.28
This work was financially supported by the National Natural
Science Foundation of China (20602015 and 20772038),
Program for Distinguish Young Scientist of Hubei Province
C(CH
3
)
3
), 1.27 (s, 18H, C(CH
Ar), 3.40 (s, 2H, OCH
s, 4H, OCH CH
3 3
)
ArCH
2
2
2
(
2
2
2
(2007ABB017) and Program for Chenguang Young Scientist
for Wuhan (200750731283).
4
6
H, ArCH
2
2
2
+
(s, 2H, ArOH); EI(+)MS m/z = 926.2 (MH2 ). Anal. calc.
for C H N O : C, 72.70; H, 7.84; N, 9.08; found: C, 72.74;
H, 7.81; N, 9.10%.
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72
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N
12
O
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28 | New J. Chem., 2009, 33, 725–728
This journal is ꢀc The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009