Calix[4]arenes containing urea and crown/urea moieties: Effects of the crown ether unit and Na+ towards anion binding ability

Article abstract of DOI:10.1016/S0040-4039(02)02530-3

Calix[4]arenes containing urea and crown/urea moieties, 7 and 10, respectively have been synthesized. ¹H NMR titrations of 7 and 10 with anions in DMSO-d₆ showed that 7 and 10 formed complexes with Cl^-, Br^-, NO<

Full text of DOI:10.1016/S0040-4039(02)02530-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 29–32
Calix[4]arenes containing urea and crown/urea moieties: effects
of the crown ether unit and Na+ towards anion binding ability
Pan Tongraung, Nuanphun Chantarasiri and Thawatchai Tuntulani*
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Received 16 September 2002; revised 28 October 2002; accepted 8 November 2002
Abstract—Calix[4]arenes containing urea and crown/urea moieties, 7 and 10, respectively have been synthesized. 1H NMR
titrations of 7 and 10 with anions in DMSO-d6 showed that 7 and 10 formed complexes with Cl−, Br−, NO3 and H2PO4 to a
different extent. The association constants of 7 and 10 towards anions were calculated and found to vary as H2PO4−>Cl−>Br−>
NO3−. However, compared to 7 the presence of the crown unit in 10 resulted in a slightly higher affinity to Cl− and Br−, but a
−
−
lower affinity to H2PO4−. Upon addition of Na+, the binding ability of 10 towards H2PO4 is increased due to ion-pair
−
enhancement. © 2002 Elsevier Science Ltd. All rights reserved.
Anion recognition is an increasingly important research
topic in supramolecular chemistry due to possible appli-
cations in selective ion receptors and sensors in biologi-
cal and environmental systems.1,2 Urea is used
dominantly in neutral anion receptors because of its
strong hydrogen bonding towards anions.3,4 Umezawa
and co-workers showed that urea receptors with a rigid
xanthene spacer formed strong complexes with dihy-
drogen phosphate.5 Very recently, cystine-based sym-
metrical cyclic oligoureas have been synthesized and
attaching urea units as receptors for anions at the wider
rim. In addition, in one of the target molecules, a
crown ether group is attached to a calix[4]arene urea on
the narrow rim. Anion binding studies of the hosts
synthesized with various anions have been performed to
investigate the effect of the crown ether unit and differ-
ent cations towards anion binding ability.
Protection and deprotection strategies have been
employed to generate a specifically functionalized
calix[4]crown urea. Syntheses of calix[4]crown ureas
were carried out as shown in Scheme 1. Calix[4]arene
was reacted with 2 equiv. of benzoyl chloride in
CH3CN in the presence of Na2CO3 as base under N2,
and the reaction was heated at reflux for 2 h to give
dibenzoyl calix[4]arene 2 in 90% yield.10 Nitration of 2
with 65% HNO3 and CH3COOH in CH2Cl2 at room
temperature yielded the dinitro compound 3 in 45%
yield.11 Methylation of 3 with CH3I in CH3CN using
Na2CO3 as base and refluxing the reaction for 5 days
resulted in the dimethyldinitro calix[4]arene 4 in 85%
yield.12 Removal of the benzoyl groups from 4 by
excess NaOH resulted in a dimethyldinitro calix[4]arene
building block 5 in 50% yield.13 Reduction of the nitro
groups in 5 with SnCl2·2H2O gave the dimethyldiamino
calix[4]arene 6 in 70% yield.14 The presence of the
methyl groups at the positions para to the amine groups
aids in stabilizing compound 6. Nevertheless, com-
pound 6 was immediately coupled with phenyl isocya-
nate in CH2Cl2 at room temperature. The white solid 7
precipitated out of the reaction in 60% yield.15 The
dimethoxydiurea calix[4]arene 7 is highly polar and
dissolves only in polar solvents such as DMF and
DMSO.
found to bind Cl−, Br− and NO3 to a different extent.6
−
Calix[4]arene is one of the most important supramolec-
ular building blocks because of its capability of being
modified at both the wide and narrow rims. Recently,
derivatives of calix[4]arene have been used as receptors
for cations, anions and neutral molecules.7 Budka et al.
have synthesized a tetra-urea derivative of calix[4]arene
in a 1,3-alternate conformation. It was found that this
receptor, with two possible binding sites, exhibited a
strong negative allosteric effect which led to the exclu-
sive complexation of only one anion.8 Reinhoudt and
co-workers demonstrated that a calix[4]arene derivative
containing ethyl ester groups and urea moieties on the
narrow rim and on the wider rim, respectively, was able
to bind Cl− efficiently in the presence of Na+.9
We are interested in synthesizing neutral anion recep-
tors using calix[4]arene as the building block and
Keywords: calix[4]arene; anion binding; ion-pair enhancement.
* Corresponding author.
0040-4039/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02530-3

30
P. Tongraung et al. / Tetrahedron Letters 44 (2003) 29–32
Scheme 1.

P. Tongraung et al. / Tetrahedron Letters 44 (2003) 29–32
31
Compound 5 underwent nucleophilic substitution with
tetraethylene glycol dimethanesulfonate in CH3CN
using Na2CO3 as base and heating at reflux for 5 days
to yield the dimethyldinitro crown calix[4]arene 8 in
45% yield.16
Reduction of the nitro groups of 8 with SnCl2·2H2O
gave the crown dimethyldiamino calix[4]arene 9 in 80%
1
yield.17 The H NMR spectra of compounds 8 and 9
showed very complicated signals in the aromatic and
alkyl proton regions that signified aryl ring inversion in
the calix[4]arene unit.18 This behavior stems from the
lack of intramolecular hydrogen bonding in 8 and 9.
The coupling reaction between 9 and phenylisocyanate
at room temperature resulted in the precipitation of the
calix[4]arene crown urea 10 in 20% yield.19 Although 10
lacks intramolecular hydrogen bonding, the sub-
stituents on the urea nitrogen prohibit the ring inver-
sion. Compound 10 is hardly soluble in common
organic solvents such as CH2Cl2 and CHCl3. It dis-
solves only in highly polar solvents such as DMSO.
Spectroscopic data and elemental analysis support the
structures of all the compounds synthesized.
Figure 1. Plots between mole ratios of anion 7 and the NH
chemical shifts.
Table 1. Association constants of ligands 7 and 10
towards H2PO4−, Cl−, Br− and NO3 using nBu4N+ as
−
countercationa
Anion
Association constants (M−1
)
7
10
We aimed to compare the binding ability of compounds
7 and 10 towards anions. Because of their importance
in environmental and biological systems, anions such as
−
H2PO4
Cl−
Br−
I−
250
43
30
No binding
13
200
60
31
No binding
11
H2PO4 , NO3 , Cl−, Br− and I−, were chosen for study.
−
−
The anion binding studies of compounds 7 and 10 were
−
NO3
1
carried out by H NMR titrations.20 Addition of tetra-
butylammonium iodide anion to a DMSO-d6 solution
of the receptors 7 and 10 did not cause any shifts of the
NH or other proton resonances which indicated that 7
and 10 could not form complexes with I−. However,
addition of a tetrabutylammonium salt of a guest anion
a All experiment were carried out at 298 K, errors estimated to be less
than 15%.
ability of anion receptors containing cation binding
units.22 Compound 10 includes a crown-5 unit which is
well known to form stable complexes with Na+.7 We
are also interested to see the effect of the ion-pair
enhancement in the binding ability of compound 10
such as H2PO4 , Cl−, Br− and NO3 to a DMSO-d6
solution of the receptors 7 and 10 resulted in significant
downfield shifts of the NH resonances at room temper-
ature, which is consistent with the formation of hydro-
gen-bonded complexes. The plots between the mole
ratios of anion: 7 and the NH chemical shift of com-
pound 7 are illustrated in Figure 1. Job plot analysis
−
−
−
towards H2PO4 . Upon adding 1.2 equiv. of NaPF6 to
a DMSO-d6 solution of the receptor 10, we observed
large chemical shifts in the region of the proton reso-
nance of the crown ether unit suggesting complex for-
mation between Na+ and the crown ether unit.
Addition of nBu4NH2PO4 to the solution caused the
NH peak to shift downfield. The association constant
was then calculated by the program EQNMR to be
1028.4 M−.1 The presence of Na+ thus increases the
indicates that 7 and 10 bind H2PO4 , Cl−, Br− and
−
−
NO3 in a 1:1 ligand/anion ratio. Association constants
of 7 and 10 towards H2PO4 , Cl−, Br− and NO3
−
−
calculated by the program EQNMR21 are collected in
Table 1.
−
The results in Table 1 indicate that both compounds 7
binding ability of 10 towards H2PO4 . Potentially, this
and 10 bind Cl−, Br−, NO3 and H2PO4 albeit to a
−
−
type of receptor can be modified to be a metal-ion
different extent. Both compounds form most stable
controlled anion receptor or sensor in the future.
−
complexes with H2PO4 and least stable complexes with
NO3 . Compound 10 binds Cl− and Br− more strongly
−
In summary, we have synthesized calix[4]arene ureas 7
and 10. Anion binding studies by 1H NMR showed that
than 7 does. However, 7 forms a more stable complex
−
−
with H2PO4 than compound 10. These results indicate
both 7 and 10 bind H2PO4 selectively. The incorpora-
that the presence of the crown bridging group in com-
pound 10 has increased the binding ability towards Cl−
and Br− slightly and decreased the binding ability
tion of the crown ether unit in the calix[4]urea results in
a slightly higher affinity of 10 for Cl− and Br−, but a
lower affinity for H2PO4 . The presence of Na+ is found
−
−
−
towards H2PO4 .
to enhance the affinity of 10 for H2PO4 . We are
currently synthesizing other derivatives of calix[4]arene
containing crowns/ureas and studying their anion bind-
ing and sensing ability. These results will be reported in
due course.
Recently, ion-pair recognition has attracted chemists’
attention. Beer and colleagues have discovered that the
presence of a suitable cation increases the binding

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P. Tongraung et al. / Tetrahedron Letters 44 (2002) 29–32
1
Acknowledgements
14. 6: H NMR spectrum (200 MHz, CDCl3) l 7.88 (s, 2H,
ArOH), 7.02 (d, J=7 Hz, 4H, ArH), 6.64 (t, J=7 Hz,
2H, ArH), 6.18 (s, 4H, ArH), 4.21 (d, J=14 Hz, 4H,
ArCH2Ar), 3.89 (s, 6H, ArOCH3), 3.27 (d, J=14 Hz, 4H,
ArCH2Ar), 1.78 (br, 4H, -NH2).
This work was financially supported by the Thailand
Research Fund (RSA/06/2544). PT is a Ph.D. student
supported by the National Science and Technology
Development Agency. We thank Professor Jeremy Kil-
burn for mass spectrometry results.
15. 7: 1H NMR spectrum (200 MHz, DMSO-d6) l 8.42 (s,
2H, ArNH-), 8.30 (s, 2H, ArNH-), 8.17 (s, 2H, ArOH),
7.08–7.33 (m, 16H, ArH), 6.89 (t, J=7 Hz, 2H, ArH),
6.60 (t, J=7 Hz, 2H, ArH), 4.15 (d, J=13 Hz, 4H,
ArCH2Ar), 3.89 (s, 6H, ArOCH3), 3.46 (d, J=13 Hz, 4H,
ArCH2Ar). ESI MS (m/z): 720.99 [M+]. Anal. calcd for 7
(C44H40 N4O6): C, 73.32; H, 5.59; N, 7.77. Found: C,
73.16; H, 5.63; N, 7.74.
References
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1
16. 8: H NMR spectrum (200 MHz, CDCl3) l 8.28–8.04 (m,
4H, ArH), 6.50–6.94 (m, 6H, ArH), 4.42 (d, J=13 Hz, 4H,
ArCH2Ar), 3.24–4.20 (m, 26H, ArOCH3, -OCH2CH2O-
and ArCH2Ar). ESI MS (m/z): 723.40 [M++Na+].
1
17. 9: H NMR spectrum (200 MHz, CDCl3) l 6.47–6.97 (m,
10H, ArH), 4.33 (d, J=12 Hz, 4H, ArCH2Ar), 4.01 (s,
6H, ArOCH3), 3.28–3.92 (m, 16H, -OCH2CH2O-), 2.99
(d, J=12 Hz, 4H, ArCH2Ar), 2.74 (br, 4H, ArNH2).
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19. 10: H NMR spectrum (200 MHz, DMSO-d6) l 8.59 (s,
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2H, ArNH-), 8.37 (s, 2H, ArNH-), 7.44 (d, J=8 Hz, 4H,
ArHph), 7.26 (t, J=8 Hz, 6H, ArHPh), 6.94 (t, J=7 Hz,
2H, ArH), 6.45–6.59 (m, 8H, ArH), 4.30 (d, J=12 Hz,
4H, ArCH2Ar), 4.03 (s, 6H, ArOCH3), 3.34–3.84 (m,
16H, -OCH2CH2O-), 3.13 (d, J=13 Hz, 4H, ArCH2Ar).
ESI MS (m/z): 901.69 [M++Na+]. Anal. calcd for
10·2H2O (C52H58N4O11): C, 68.26; H, 6.39; N, 6.12.
Found: C, 68.05; H, 5.96; N, 6.65.
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1
10. 2: H NMR spectrum (200 MHz, CDCl3) l 8.36 (d, J=8
Hz, 4H, ArHbenzoyl), 7.72 (t, J=8 Hz, 2H, ArHbenzoyl),
7.53 (t, J=8 Hz, 4H, ArHbenzoyl), 7.07 (d, J=4 Hz, 4H,
ArH), 6.66–6.94 (m, 8H, ArH), 5.50 (s, 2H, ArOH), 3.98
(d, J=14 Hz, 4H, ArCH2Ar), 3.52 (d, J=14 Hz, 4H,
ArCH2Ar).
20. Solutions of 7 and 10 (0.01 M) in DMSO-d6 were pre-
pared. To a solution of a ligand in each NMR tube was
added 0.0–4.0 equiv. of a 0.25 M tetrabutylammonium
salt of the anion. The result of the experiment was a plot
of displacement in chemical shift as a function of the
amount of added anion. The program EQNMR was then
used to analyze the resulting titration curves and to
1
11. 3: H NMR spectrum (200 MHz, CDCl3) l 8.21 (d, J=8
Hz, 4H, ArH), 7.97 (s, 4H, ArH), 7.76 (t, J=7 Hz, 2H,
ArH), 7.53 (t, J=7 Hz, 4H, ArH), 7.01 (m, 6H, ArH),
6.33 (s, 2H, ArOH), 3.99 (d, J=14 Hz, 4H, ArCH2Ar),
3.66 (d, J=14 Hz, 4H, ArCH2Ar).
1
calculate stability constant values in M−1
.
12. 4: H NMR spectrum (200 MHz, CDCl3) l 6.75–8.19 (m,
21. Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311.
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B. Chem. Commun. 1998, 231; (b) Beer, P. D.; Hopkins,
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Dalton Trans. 2000, 2721.
20H, ArH), 3.35–3.82 (m, 14H, ArOCH3, ArCH2Ar).
13. 5: H NMR spectrum (200 MHz, CDCl3) l 7.80 (s, 4H,
1
ArH), 7.52 (s, 2H, ArOH), 7.14 (d, J=7 Hz, 4H, ArH),
6.75 (t, J=6 Hz, 2H, ArH), 4.33 (d, J=13 Hz, 4H,
ArCH2Ar), 4.05 (s, 6H, ArOCH3), 3.51 (d, J=13 Hz, 4H,
ArCH2Ar). FAB MS (m/z): 542.84 [M+].