A new water-soluble ligand based on a calix[4]arene substituted by 2,2′-bipyridine chelating units

Article abstract of DOI:10.1016/S0040-4039(01)00306-9

A new water-soluble calix[4]arene-based podand was prepared by tethering two 4,4′-dicarboxy-2,2′-bipyridine units on distal phenol rings.

Full text of DOI:10.1016/S0040-4039(01)00306-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2799–2800
A new water-soluble ligand based on a calix[4]arene substituted
by 2,2%-bipyridine chelating units
Nicolas Psychogios and Jean-Bernard Regnouf-de-Vains*
GEVSM, UMR 7565 CNRS- UHP, Faculte´ de Pharmacie, 5, rue Albert Lebrun, F-54001 Nancy, France
Received 21 February 2001
Abstract—A new water-soluble calix[4]arene-based podand was prepared by tethering two 4,4%-dicarboxy-2,2%-bipyridine units on
distal phenol rings. © 2001 Elsevier Science Ltd. All rights reserved.
Water-soluble calixarenes are mainly prepared by direct
or indirect incorporation, at the lower and upper rims,
of various types of polar functions such as, for exam-
ple, carboxylate,1,2 sulfonate,3 phosphonate4 or alky-
lamino groups.2,5
groups brought by the bipyridine units. This led to the
new water-soluble ligand 5 described here (Scheme 1).
Reaction of 1 equiv. of m-CPBA on the 6,6%-dimethyl-
4,4%-dicarbomethoxy-2,2%-bipyridine 1 gave the mono-
N-oxyde 2. Unstable on chromatographic supports, 2
was directly transformed via a Boeckelheide rearrange-
ment in the non-isolated 6-trifluoroacetyl analogue,
which, upon reaction with LiBr in a polar aprotic
solvent, gave the desired monobromide 3 with a yield of
With the aim to translate into water complexation
experiments previously developed with lipophilic calix-
arene-based bipyridine podands,6 we attempted to
introduce a hydrophilic behaviour via carboxylate
O
O
O
O
O
O
O
O
O
O
O
O
ii
i
N
N
N
N
N
N
3
1
2
O
Br
iii
iiii
O
O
OH
OH
HO
HO
O
O
O
O
O
O
O
Na+ , -O
Na+ , -O
O
O
O- , Na+
O
O
N
N
N
N
N
N
, 2 NaCl, 6 H2O
O- , Na+
N
N
O
O
4
5
O
Scheme 1. (i) m-CPBA, CH2Cl2, 90%; (ii) (a) (CF3CO)2O; (b) LiBr, THF, DMF, 55%; (iii) calix[4]arene, MeCN, K2CO3, reflux,
83%; (iiii) NaOH, H2O, EtOH, reflux, 80%.
* Corresponding author. Fax: (33)3 83 17 90 57; e-mail: jean-bernard.regnouf@pharma.u-nancy.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00306-9

2800
N. Psychogios, J.-B. Regnouf-de-Vains / Tetrahedron Letters 42 (2001) 2799–2800
3Na+]3−/3 and 503.24 a.m.u. [5−2Na+]2−/2]. The
mono-charged species was observed in the positive
mode at 1075.98 a.m.u. [5+Na+]+.
To give a preliminary concrete form to this synthetic
work, the complexation of Cu(I) by 5 was followed in
water by UV–visible spectroscopy (Fig. 2). The metal-
to-ligand charge transfer band which appeared at 470
nm, as expected with tetrahedral Cu(I)/diimine com-
plexes, was completed on the addition of 1 equiv. of
Cu(I), suggesting, as for parent hydrophobic ligands,6,8
the formation of a mononuclear complex involving
coordination of both bipyridine units. Even after 24 or
48 h, or in the presence of BSA, this band remained
unchanged, proving that 5 was able to stabilise Cu(I) in
water and probably in biological media. This specific
behavior and the complexation of various metal species
by 5 are currently under investigation.
Figure 1. 1H NMR spectrum of 5 (D2O, 400 MHz, rt).
Acknowledgements
We are grateful to the MRES and to the CNRS for
financial support, to SAFAS (Monaco) and to Bruker
for UV spectroscopy and WinNMR facilities, respec-
tively. The authors thank Mrs Nicole Marshall for
correcting the manuscript.
Figure 2. UV–visible titration of 5 by Cu(MeCN)4PF6. (a) 5,
1.71×10−5 M in H2O; (k) 5+1 equiv. of Cu(I).
References
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55% versus 2. Calix[4]arene-tetrol,7 3 and K2CO3
reacted in refluxing MeCN8 to give the podand 4 which
was finally saponified. Acidification to pH 3–4 (1 M
HCl), followed by a controlled neutralisation with
NaOH, afforded the tetra-carboxylate 5 with a yield of
80%. All compounds gave satisfactory C, H, N, IR, MS
and NMR analyses. In particular, the elemental analy-
sis of 5 was consistent with the presence of two
1
molecules of NaCl and six molecules of H2O. The H
NMR analysis of 5 in D2O showed the presence of six
bipyridyl and five calixarene signals, all perfectly well
resolved, which confirmed the expected structure (Fig.
1). 13C NMR spectra showed that 5 was in the cone
conformation,9 with Ar-CH2-Ar signals at 30.79 ppm.
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ited three signals at 240.04 [5−4Na+]4−/4, 327.87 [5−