Aza crown ether calix[4]arenes containing cation and anion binding sites: Effects of metal ions towards anion binding ability

Article abstract of DOI:10.1016/S0040-4039(01)01029-2

Tripodal aza crown ether calix[4]arenes containing both cation and anion binding sites (5a and 5b) have been synthesized. The X-ray analysis shows that 5a forms a self-threaded rotaxane-like structure in the solid state. ¹H NMR titrations of the two ligands with various halide anions indicate that 5a and 5b can form complexes with Br^- and I^- but not F^-. However, both compounds form more stable complexes with I^- than with Br^- in the presence of Bu₄N⁺. The presence of K⁺ enhances the binding ability of 5a towards Br^-.

Full text of DOI:10.1016/S0040-4039(01)01029-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5541–5544
Aza crown ether calix[4]arenes containing cation and anion
binding sites: effects of metal ions towards anion binding ability
Thawatchai Tuntulani,a,* Sirilux Poompradub,a Praput Thavornyutikarn,a Nongnuj Jaiboon,a
Vithaya Ruangpornvisuti,a Narongsak Chaichit,b Zouhair Asfaric and Jacques Vicensc
aDepartment of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
bDepartment of Physics, Faculty of Science, Thammasat University at Rangsit, Pathumthani 12121, Thailand
cECPM, Group de Chimie des Interactions Mole´culaires Spe´cifiques, associe´ au CNRS, 25, rue Becquerel,
F-67087 Strasbourg Cedex 2, France
Received 14 May 2001; accepted 8 June 2001
Abstract—Tripodal aza crown ether calix[4]arenes containing both cation and anion binding sites (5a and 5b) have been
1
synthesized. The X-ray analysis shows that 5a forms a self-threaded rotaxane-like structure in the solid state. H NMR titrations
of the two ligands with various halide anions indicate that 5a and 5b can form complexes with Br− and I− but not F−. However,
both compounds form more stable complexes with I− than with Br− in the presence of Bu4N+. The presence of K+ enhances the
binding ability of 5a towards Br−. © 2001 Elsevier Science Ltd. All rights reserved.
Molecular recognition of abiotic anions by synthetic
receptors has received increasing attention in the past
few years according to recent reviews written by Beer
and Gale.1 Many receptors have been used successfully
as sensors for anions.2 Recently, synthetic receptors
containing two individual recognition sites for a cation
and an anion have attracted chemists’ attention. Appli-
cations of such receptors may be found in metal-con-
trolled anion sensing devices. Reinhoudt and
amino)ethylamine, tren and glycolic chains to obtain
compounds that have both a cation and an anion
binding site in the same molecule. This compound may
have great potential to bind a metal ion and an anion
cooperatively and selectively.
Tripodal aza crown ether calix[4]arenes, 5a and 5b,
were synthesized according to the procedure shown in
Scheme 1. Substitution reactions of p-tert-butyl-
calix[4]arene with 3.0 equiv. of 2-(2%-bromoethoxy)-
benzaldehyde, 1a, and 4-(2%-bromoethoxy)benzaldehyde,
1b, respectively, were carried out in the presence of a
base to produce trialdehyde precursors, 3a and 3b, for
preparing the tripodal amine capped calix[4]arene. The
synthesis of 3a was reported previously in acetonitrile
using K2CO3 as base. This reaction gave only 6% yield
of the desired trialdehyde derivative.6 Furthermore,
substitution reactions using K2CO3 always gave the
dialdehyde derivatives, 2a and 2b, in high yields.7 Since
then, a number of bases and solvents have been
employed to optimize the yields of the desired products.
However, it was found that in the presence of strong
bases such as NaH and KOH the aldehydes underwent
Cannizzaro reactions and gave both alcohol and car-
boxylic acid derivatives instead.8 Finally, we found that
reactions using BaO in DMF gave higher yields of
trialdehyde calix[4]arenes, 3a6 (21%) and 3b9 (46%),
than those of dialdehyde calix[4]arenes, 2a (20%) and
2b (2%). It should be noted that the yield of 3b was
co-workers have elegantly demonstrated that
a
calix[4]arene derivative with cation binding ester groups
on the lower rim and anion binding ureas on the upper
rim can efficiently bind Cl− only in the presence of
Na+.3 Beer and coworkers have synthesized a number
of ditopic receptors that can undergo selective ion pair
recognition.4
In 1997, polyaza crown ether derivatives of p-tert-
butylcalix[4]arene were synthesized in our lab. The
ammonium derivatives were found to form complexes
with CO32−, NO3 , AsO2 and Cl− to a different extent
using electrostatic interactions.5 We are interested in
constructing a three dimensional anion receptor by
combining the calix[4]arene framework with tris(2-
−
−
Keywords: aza crown; calix[4]arene; anion binding; proton NMR
titration.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01029-2

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T. Tuntulani et al. / Tetrahedron Letters 42 (2001) 5541–5544
Scheme 1. Synthetic procedure of compounds 5a and 5b.
twice as much as that of 3a probably due to the less
steric hindrance of the para isomer facilitating the
substitution reaction. Compounds 2 and 3 were sepa-
rated by silica-gel chromatography using CH2Cl2 as
eluent. Condensation reactions of 3a and 3b with 1.1
equiv. of tris(2-amino)ethylamine in acetronitrile pre-
cipitated the imine or Schiff base products, 4a6 (95%)
and 4b10 (97%). Reduction of 4a and 4b by 20 equiv. of
NaBH4 and subsequent acidification with HCl/CH3OH
(0.74% v/v) yielded the desired tripodal ammonium
chains.11 Both 5a and 5b possess N4-tripodal ammo-
nium units for binding anions and O6-crown ether
cavities for binding alkali cations. However, the N4-
tripodal ammonium cavity of the para isomer, 5b,
should have more space than that of the ortho isomer,
5a. This leads to the different selectivity of 5a and 5b
towards various anions.
1
derivatives, 5a6 (86%) and 5b11 (95%). The H NMR
spectra of compounds 3b–5b possessed four sets of
doublets due to the methylene bridge protons on the
calix[4]arene moiety suggesting the existence of the cone
conformation.
The solid state structure of compound 5a has been
determined by X-ray crystallography (Fig. 1).12 The
calix[4]arene unit is in a pinched cone conformation.
One of the ethoxy benzyl chains connecting to the tren
unit threads through the cavity of the other two ethoxy
benzyl chains. This structure resembles a self-threaded
rotaxane derivatised from two homooxacalix[3]arenes.13
Recently, Vicens and colleagues have also reported a
similar structure of tripodal calix[4](azo)crowns.14
Although suitable crystals of 5b for X-ray analysis
1
could not be obtained, the H NMR spectrum of 5b
Figure 1. Crystal structure of 5a. Hydrogen atoms are omit-
ted for clarity.
suggests a more symmetrical orientation of the glycolic

T. Tuntulani et al. / Tetrahedron Letters 42 (2001) 5541–5544
5543
to -OArCH2NH+2- and –OArHCH2-. The plot showing
the relationship between chemical shifts of the signal
due to –OArHCH2- and concentrations of iodide anion
is depicted in Fig. 2. Job plot analysis indicates that 5a
and 5b bind Br− and I− in a 1:1 ligand/anion ratio.
Association constants of 5a and 5b towards Br− and I−
in the presence of various countercations such as Bu4N+,
Na+ and K+ calculated by the program EQNMR16 are
collected in Table 1.
The result implies that the tripodal ammonium cavities
of 5a and 5b are not suitable for binding F−. With
Bu4N+ as countercation, 5a and 5b can form more
stable complexes with I−. However, the stability of 5b
towards I− is higher than 5a. This signifies that the
cavity of 5b is more suitable for binding a big anion
such as I−. In the presence of K+, 5a shows an increase
in binding affinity towards Br− by nearly 1.5 fold. On
the other hand, Na+ does not show any enhancement in
the anion binding ability of 5a. The result suggests that
the crown ether unit of 5a prefers binding K+ over Na+.
A similar crown ether cavity found in a biscalix[4]arene
in which two molecules of calix[4]arene are linked by
four glycolic units has been reported to bind K+ selec-
tively.17 From the crystal structure of 5a, it is also
possible that an alkali metal ion can coordinate to the
crown ether unit and induce the structural reorganiza-
tion of 5a to be more appropriate for binding anions
(Scheme 2). Interestingly, the binding ability of 5b
towards Br− and I− decreases in the presence of Na+
and K+. An observation in which the presence of alkali
metal ions decreases the anion binding ability of 5a and
5b can be rationalized in terms of the binding competi-
tion. Alkali metal ions (Na+ or K+) that cannot fit into
the cavity size of the crown ether unit in 5a or 5b retain
alkali metal–anion pairs and compete in binding with
the tripodal ammonium unit of the ligands.
Figure 2. Titration curves of 5b with I− in the presence of
Bu4N+, Na+ and K+.
Table 1. Association constants of ligands 5a and 5b
towards Br− and I− in the presence of various
countercationsa
Metal
Anion
Kassoc (M−1
)
5a
84.2
58.6
120.1
108.9
77.2
5b
76.5
53.0
34.9
137.9
57.3
66.3
Noneb
Na+
K+
Br−
Br−
Br−
I−
Noneb
Na+
K+
I−
I−
103.3
a All experiments were carried out at 298 K, errors estimated to be
less than 15%.
b Using Bu4N+ as countercation.
In summary, we have synthesized two tripodal aza
crown ether calix[4]arenes, 5a and 5b, and shown that
both can bind Br− and I− to a different extent depend-
ing on countercations. We are currently investigating
the complexation of 5a and 5b towards other anions
and also preparing new ion pair receptors for better
understanding of such cooperative behavior and for
possible applications in metal ion-controlled anion
extraction.
Supplementary material
Scheme 2. A metal ion can possibly induce the structural
reformation of 5a to bind an anion more efficiently.
Crystallographic data for 5a are available upon request
from the Cambridge Crystallographic Data Base
(CCDC 165241).
1H NMR (200 MHz) titrations were employed in com-
plexation studies of 5a and 5b towards halide anions
(F−, Br− and I−) in the presence of various counter-
cations.15 It was found that no displacement of any
proton signals of 5a and 5b occurred upon addition of
F−. This result indicates that 5a and 5b do not form
complexes with F−. Addition of Br− and I− to 5a and
5b, however, resulted in the displacement of signals due
Acknowledgements
This work was financially supported by the Thailand
Research Fund (Grant no. PDF4080055). The authors
thank Professor Michael J. Hynes for providing the
program EQNMR.

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T. Tuntulani et al. / Tetrahedron Letters 42 (2001) 5541–5544
(d each, JH–H=13.0 Hz, 4H, ArCHAHBAr), 4.28–4.02
References
(m, 10H, OCH2CH2O), 3.74 (m, 4H, CHꢀNCH2CH2N),
3.64 (m, 2H, CHꢀN CH2CH2N), 2.83 (m, 4H,
CHꢀNCH2CH2N), 2.59 (m, 2H, CHꢀNCH2 CH2N), 1.39
(s, 9H, HOAr-t-C4H9), 1.36 (s, 9H, ROAr-t-C4H9), 0.83
(s, 18H, ROAr-t-C4H9). Anal. calcd for 4b (C77H92N4O7):
C, 78.01; H, 7.82; N, 4.73%. Found: C, 77.95; H, 7.66; N,
4.77%.
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11. Compound 5b: H NMR spectrum (500 MHz, CDCl3): l
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8.71 and 8.23 (s each, broad, 4H and 2H, ArCH2NH+2Cl−),
7.79 (d, JH–H=8.6 Hz, 4H, -OArHa), 7.36 (d, JH–H=8.5
Hz, 2H, -OArHa), 7.14 (s, 2H, HOArH), 7.10 (s, 2H,
ROArH), 6.92 (d, JH–H=8.7 Hz, 4H, -OArHb), 6.54 (m,
6H, ROArH and -OArHb), 6.12 (s, 1H, HOAr), 4.56 and
3.30 (d each, JH–H=13.3 Hz, 4H, ArCHAHBAr), 4.55-
4.40 (m, 14H, OCH2CH2O, ArCH2N and ArCHAHBAr),
4.20–3.98 (m, 6H, OCH2CH2O, ArCH2N), 3.70 (s, br,
2H, NCH2CH2N), 3.41–3.10 (m, 10H, NCH2CH2N), 3.25
(d, JH–H=13.0 Hz, 2H, ArCHAHBAr), 1.34 (s, 9H,
HOAr-t-C4H9), 1.32 (s, 9H, ROAr-t-C4H9), 0.82 (s, 18H,
ROAr-t-C4H9). Anal. calcd for 5b (C77H102N4O7Cl4): C,
69.15; H, 7.69; N, 4.19%. Found: C, 69.19; H, 7.76; N,
4.16%.
12. Crystal data for 5a, C77H102N4O7Cl2(OH)2·(CH3OH)-
(H2O)2, M=1368.7, monoclicnic, space group C2/c, Z=
8. Sukwattanasinitt, M.; Rojanathanes, R.; Tuntulani, T.;
Ruangpornvisuti, V., accepted for publication in Science
Asia.
,
8, a=43.6552 (14), b=15.9085 (5), c=25.1856 (7) A,
3
3−
,
i=109.4630 (10)°, V=16491.6 (9) A , Dc=1.119 g cm
23606 unique data, R1=0.1355, wR2=0.3402.
,
1
9. Compound 3b: H NMR spectrum (500 MHz, CDCl3): l
9.76 and 9.68 (s each, 2H and 1H, -Ar(CꢀO)H), 7.57 and
7.43 (d each, JH–H=8.7 Hz, 4H and 2H, -OArHa), 7.19
(s, 2H, HOArH), 7.14 (s, 2H, ROArH), 6.70 and 6.63 (d
each, JH–H=8.7 Hz, 4H and 2H, -OArHb), 6.54 (s, 4H,
ROArH), 5.40 (s, 1H, HOAr), 4.86 (m, 2H,
OCH2CH2O), 4.45 and 3.32 (d each, JH–H=12.4 Hz, 4H
each, ArCHAHBAr), 4.28 (m, 2H, OCH2CH2O), 4.13 (s,
8H, OCH2CH2O), 1.36 (s, 18H, HOAr-t-C4H9 and
ROAr-t-C4H9), 0.82 (s, 18H, ROAr-t-C4H9). FAB MS
(m/z): 1092.5. Anal. calcd for 3b (C77H80O10): C, 77.99;
H, 7.37%. Found: C, 77.91; H, 7.52%.
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M) in DMSO-d6 and in a mixture of CDCl3 and CD3OD,
respectively, were prepared. To a solution of a ligand in
each NMR tube was added 0.0–4.0 equiv. of 0.1 M anion
salts. Spectra were recorded every 24 h until the complex-
ation reached the equilibrium. The result of the experi-
ment was a plot of displacement in chemical shift as a
function of the amount of added anion. The program
EQNMR was then used to analyse the resulting titration
curves and calculate stability constant values for 1:1
anion complexes in M−1. Titration experiments were
repeated twice with at least 12 data points for each anion.
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1
10. Compound 4b: H NMR spectrum (500 MHz, CDCl3): l
8.07 and 7.86 (s each, 1H and 2H, -CHꢀN), 7.38 (d,
JH–H=8.7 Hz, 4H, -OArHa), 7.20 (s, 2H, HOArH), 7.18
(s, 2H, ROArH), 6.73 (d, JH–H=8.7 Hz, 4H, -OArHb),
6.62 (d, JH–H=2.4 Hz, 2H, ROArHa), 6.52 (d, JH–H=2.4
Hz, 2H, ROArHb), 6.32 (s, 1H, HOAr), 6.13 (d, JH–H
=
8.8 Hz, 2H, ROArH), 6.02 (d, JH–H=8.8 Hz, 2H,
ROArH), 4.92 and 3.32 (d each, JH–H=13.0 Hz, 4H,
ArCHAHBAr), 4.56 (m, 2H, OCH2CH2O), 4.33 and 3.23
.