Chloride recognition in aqueous media by a rotaxane prepared via a new synthetic pathway

Article abstract of DOI:10.1002/chem.200802029

The preparation of a novel rotaxane, which consists of a pyridyl macrocycle wheel and pyridinium axle components, by a new synthetic pathway that involves anion templation in combination with favorable π-π stacking interactions was studied. The synthesis of new rotaxane 6-Cl was achieved by the addition of 3,5-bis(chlorocarbonyl) pyridine to a mixture of bis-amine, Et₃N, and the stoppered axle component 5-Cl in CH₂Cl₂. Simple variation of the nature of the acid chloride can lead to a range of rotaxanes being prepared which contain interlocked cavities of variable dimensions and rotaxane was isolated in 32% yield following preparative thin-layer chromatography. The new rotaxane's impressive selective recognition of chloride in aqueous solvent media highlights the real potential such interlocked molecular host systems might have in anion chemical sensor technological applications.

Full text of DOI:10.1002/chem.200802029

DOI: 10.1002/chem.200802029
Chloride Recognition in Aqueous Media by a Rotaxane Prepared via a New
Synthetic Pathway
[
a]
Laura M. Hancock and Paul D. Beer*
In spite of the rapid growth of the anion supramolecular
[1]
chemistry field in recent years, the strategic use of anions
as templating reagents for the designed assembly of molecu-
[2]
lar architectures remains largely underdeveloped. This
maybe a consequence of their perceived diffuse nature
(
small charge/radius ratio), pH dependence, and high solva-
tion energies. In particular this is especially the case in the
construction of mechanically bonded molecules which have
potential nanotechnological applications as molecular
[3]
switches, machines, and sensors. Regarding the latter we
have undertaken a research program with the objective of
exploiting the unique topological cavities of rotaxanes and
Figure 1. Schematic representation of rotaxane synthesis.
[4]
catenanes in anion host–guest chemistry. By coupling
anion recognition with ion-pairing we have utilized the chlo-
ride anion to facilitate the interpenetration of pyridinium,
imidazolium, and guanidinium cationic threads through the
annulus of an isophthalamide macrocycle. This has led to
the chloride anion templated preparation of rotaxane and
for chloride in aqueous solvent media in preference to basic
oxoanions.
Whilst investigating the synthesis of the target pyridyl-
containing macrocycle 3 by the condensation reaction of bis-
[7]
amine 1 with 3,5-bis(chlorocarbonyl) pyridine 2 in dry
[5]
catenane systems by Grubbsꢀ first-generation catalyzed
CH Cl , the yield of macrocyclization doubled from 21% to
2
2
[6]
ring-closing metathesis (RCM) reactions. Despite the suc-
cess achieved in the synthesis of these interlocked structures
by RCM, there are various limitations to using Grubbsꢀ
first-generation catalyst, such as incompatibility with certain
ligating functional groups capable of coordinating to the
ruthenium metal like pyridyl, that necessitates the explora-
tion of alternative synthetic routes. Herein we describe the
preparation of a novel [2]rotaxane, which consists of a pyrid-
yl macrocycle wheel and pyridinium axle components, by a
new synthetic pathway that involves anion templation in
combination with favorable p–p stacking interactions
42% when the reaction was undertaken in the presence of
[8]
3,5-bis-hexylamide-substituted pyridinium derivative 4-Cl
(Scheme 1). This suggests favorable p–p stacking between
the positively charged electron-deficient pyridinium group
(
Figure 1). In addition preliminary anion binding studies
reveal that the rotaxane exhibits an impressive high affinity
[
a] L. M. Hancock, Prof. Dr. P. D. Beer
Inorganic Chemistry Laboratory
Department of Chemistry, University of Oxford
South Parks Road, Oxford, OX1 3QR (UK)
E-mail: paul.beer@chem.ox.ac.uk
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200802029.
Scheme 1. Synthesis of macrocycle 3.
42
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Chem. Eur. J. 2009, 15, 42 – 44

COMMUNICATION
of 4-Cl and the electron-rich hydroquinone motifs of 1 to-
gether with chloride anion templation preorganize the ter-
minal amine functional groups of 1 to favor macrocycle for-
mation.
Indeed given the observed strength of pseudorotaxane
4
À1
formation between macrocycle 3 and 4-Cl, K>10 m in
1
CD Cl as determined by H NMR titration experiments, it
2
2
was of interest to investigate whether [2]rotaxanes could be
synthesized by simply replacing 4-Cl with an appropriate
pyridinium-stoppered axle under the condensation reaction
conditions described in Scheme 1.
The synthesis of new [2]rotaxane 6-Cl was achieved by
the addition of 3,5-bis(chlorocarbonyl) pyridine 2 to a mix-
ture of bis-amine 1, Et N, and the stoppered axle component
3
[5a]
5
-Cl
in CH Cl (Scheme 2). The rotaxane was isolated in
2 2
32% yield following preparative thin-layer chromatography.
1
3
Figure 2. H NMR spectra in CDCl at 293 K of a) axle 5-Cl, b) [2]ro-
taxane 6-Cl, and c) macrocycle 3.
by downfield shifts of the amide c and cavity isophthalamide
proton b as they become deshielded by the halideꢀs negative
charge. The proton signal associated with the hydroquinone
environments, f and g, of the macrocycle has moved upfield
and split appreciably which is characteristic of p–p donor-
acceptor interactions between the electron-rich hydroqui-
nones and the positively charged electron-deficient pyridini-
um motif. Finally, the signal corresponding to the methyl
protons l of the pyridinium axle has moved significantly up-
field, indicative of hydrogen bonding between these protons
and the oxygen atoms of the macrocycleꢀs polyether chain.
Further characterization of the structure of [2]rotaxane 6-
1
3
1
Cl was obtained from ESMS, C NMR, and 2D H NMR
ROESY spectroscopy (see Supporting Information).
To probe the anion binding cavity of [2]rotaxane 6 it was
necessary to remove the chloride anion from the interlocked
binding domain. It was exchanged for the non-coordinating
hexafluorophosphate anion in quantitative yield by repeated
washing of a solution of 6-Cl in CHCl with NH PF solu-
6(aq)
3
4
tion. Anion exchange was observed to have no significant
effect on the position of the cationic pyridinium axle compo-
nent within the pyridyl macrocyclic wheel, as demonstrated
by the observed splitting of hydroquinone protons, f and g,
1
in the H NMR spectra of 6-PF . The only significant differ-
6
1
ence in the CDCl3 H NMR spectra of the two rotaxanes is
Scheme 2. Synthesis of [2]rotaxane 6-Cl
.
both sets of amide signals are observed to move significantly
upfield upon removal of the chloride templating anion.
The anion binding properties of the rotaxane 6-PF were
6
À
À
À
4
Evidence for the formation of the [2]rotaxane was initially
investigated by titrating with TBA salts of Cl , Br , H PO ,
2
and OAc initially in 1:1 CDCl :CD OD. The chemical shift
3 3
1
À
obtained by H NMR spectroscopy. The spectrum of rotax-
ane 6-Cl, along with those of the component macrocycle 3
and axle 5-Cl for comparison are shown in Figure 2.
perturbations of the ortho-pyridinium proton m and para-
pyridinium proton n were monitored as a function of the
[9]
The [2]rotaxane 6-Cl displays considerable upfield shifts
of the amide protons o and para-pyridinium proton n corre-
sponding to polarization of the chloride ion away from the
binding cleft as a result of halide anion recognition by the
macrocycleꢀs isophthalamide cavity. This is further signified
equivalents of anion added. WinEQNMR analysis of the
titration data gave association constant values for 1:1 rotax-
ane/anion stoichiometric complexes shown in Table 1.
The rotaxane is selective for chloride in preference to the
more basic oxoanions. It is noteworthy that chloride is very
Chem. Eur. J. 2009, 15, 42 – 44
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
43

P. D. Beer and L. M. Hancock
À
À
Table 1. Association constants, K, of [2]rotaxane 6-PF
6
with Cl , Br ,
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<
M->
À
H
2
PO
4
,
and OAc
in 1:1 CDCl
3
:CD OD, and 45:45:10
3
CDCl
3
:CD
3
OD:D
2
O at 293 K. Error <10%.
À
À
4À
À
Anion
Cl
Br
H
2
PO
OAc
520
À1
4
[a]
K (m ) in
>10
–
720
60
1
:1 CDCl
3
:CD
3
OD
À1
K (m ) in
1500
780
110
4
5:45:10 CDCl
3
3 2
:CD OD:D O
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vent medium the rotaxane is an efficient complexant of
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acid chloride condensation reaction results in rotaxane for-
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tion of chloride in aqueous solvent media highlights the real
potential such interlocked molecular host systems might
have in anion chemical sensor technological applications.
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Acknowledgement
1
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[
[
Keywords: anions · molecular recognition · rotaxanes ·
supramolecular chemistry · template synthesis
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Received: October 2, 2008
Published online: November 28, 2008
44
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Chem. Eur. J. 2009, 15, 42 – 44