A [2]catenane containing an upper-rim functionalized calix[4]arene for anion recognition

Article abstract of DOI:10.1016/j.tetlet.2009.02.212

A novel [2]catenane is synthesized in good yield from an upper-rim functionalized calix[4]arene macrobicycle and a nitro-substituted isophthalamide threading component in the presence of a chloride anion template via a ring-closing metathesis (RCM) reaction. After halide anion template removal the resulting catenane host exhibits a high degree of selectivity for chloride in competitive organic solvent mixtures.

Full text of DOI:10.1016/j.tetlet.2009.02.212

Tetrahedron Letters 50 (2009) 3454–3457
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A [2]catenane containing an upper-rim functionalized calix[4]arene
for anion recognition
*
Dale E. Phipps, Paul D. Beer
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel [2]catenane is synthesized in good yield from an upper-rim functionalized calix[4]arene macro-
bicycle and a nitro-substituted isophthalamide threading component in the presence of a chloride anion
template via a ring-closing metathesis (RCM) reaction. After halide anion template removal the resulting
catenane host exhibits a high degree of selectivity for chloride in competitive organic solvent mixtures.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 18 December 2008
Revised 13 February 2009
Accepted 26 February 2009
Available online 4 March 2009
Keywords:
Catenane
Calixarene
Anion recognition
Supramolecular chemistry
Interlocked structures, in particular rotaxanes and catenanes,
have long held the interest of the supramolecular community.1,2
While originally thought of as just a curiosity due to their aesthet-
ically pleasing and topologically interesting nature, the construc-
tion of interlocked systems of increasing complexity and
functionality has become, in itself, a leading area of research.
Although there is currently much interest in the incorporation of
rotaxanes and catenanes into molecular switches and ma-
chines,3–6 the potential of these molecules to function as selective
host systems in molecular recognition applications has been lar-
gely overlooked. This is somewhat surprising given their unique
three-dimensional topological binding cavities. Indeed, using anion
templation we have recently synthesized a variety of interlocked
host structures which exhibit high degrees of selectivity toward
chloride7–9 and sulfate10,11 guest species.
Calixarenes are well-defined molecular scaffolds that are re-
nowned for their versatility and ease of functionalization at both
the lower and upper rims.12 As such, the use of these structures
in interlocked assemblies has attracted much interest over the
years. For example, these versatile molecules have been used as
both molecular wheels13–16 and stoppers17 in the formation of
rotaxanes. Meanwhile their pre-organized nature and ability to
encapsulate guests18 have led to the development of tetraurea
hydrogen-bonded dimers that have been subsequently used in
the synthesis of a series of multicyclic catenanes19–21 and rotax-
anes.22,23 Furthermore, incorporation of both electron-rich24,25
and electron-poor26,27 aromatic systems into the calixarene frame-
work has led to a number of catenanes utilizing
interactions.
p–p stacking
With the longer term aim of fabricating interlocked host sys-
tems onto surfaces for anion sensory device applications28 we have
begun to incorporate the calix[4]arene framework into catenane
molecular structures. In our first example, a lower-rim functional-
ized calix[4]arene [2]catenane was prepared.29 Herein we describe
the synthesis of a novel [2]catenane containing an upper-rim func-
tionalized calix[4]arene via exploitation of a strategic anion tem-
plation methodology.30,31
Synthesis of the new upper-rim calix[4]arene macrobicyclic
component of the catenane 5b is depicted in Scheme 1. Starting
from calix[4]arene,32 the upper-rim bis acid-functionalized ca-
lix[4]arene 1 was prepared, using the literature procedures.33–35
Conversion of 1 into the activated pentafluorophenol (PFP) ester
derivative 2 was achieved utilizing dicyclocarbodiimide (DCC) as
a coupling reagent in dichloromethane. Treatment of 2 with
2-(4-(2-azidoethoxy)phenoxy)ethanamine (see Supplementary
data) in the presence of triethylamine resulted in the formation
of a bis-azide which, upon reduction with hydrogen, gave the
bis-amine 3. Reaction of this species under high dilution conditions
with pyridine-3,5-dicarbonyl dichloride gave upper-rim function-
alized calix[4]arene macrobicycle 4 in 50% yield (see Supplemen-
tary data) which was subsequently alkylated with methyl iodide
to give the pyridinium-derivatized macrocycle 5a. Anion exchange
using saturated aqueous ammonium chloride solution afforded the
calix macrobicycle as the desired chloride salt 5b, as confirmed by
the respective downfield shifts of protons Hb and Hc due to stron-
ger hydrogen-bonding interactions with chloride.
* Corresponding author. Tel.: +44 0 1865 285 142; fax: +44 0 1865 272690.
E-mail address: paul.beer@chem.ox.ac.uk (P.D. Beer).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.212

D. E. Phipps, P. D. Beer / Tetrahedron Letters 50 (2009) 3454–3457
3455
OPFP
OH
PFPO
HO
O
O
O
O
i)
O
OO
O
O
O
O
O
OEt
OEt
OEt
OEt
EtO
EtO
EtO
EtO
2
1
ii)
O
iii)
OEt
OEt
H2N
H2N
O
O
O
N
H
O
O
O
O
H
N
OEt
OEt
O
O
3
(iv) (v)
O
Figure 1. Partial 1H NMR spectra (500 MHz, CDCl3, 293 K) of (a) macrocycle 5b, (b)
5b and 1 equiv of 6 and (c) free thread 6.
OEt
O
NH O
O
O
N
a
OEt
h
g
H
O
O
N
X
b
e
additional hydrogen-bonding interactions to the nitro group of
the thread.
O
O
d d'
c
H
OEt
OEt
f
N
NH O
Encouraged by this evidence of anion-templated pseudorotax-
ane assembly, attempts were made to ring-close the thread to form
the target catenane. The catenation reaction was undertaken by
the addition of Grubbs’ second generation ring-closing metathesis
(RCM) catalyst to a stirring solution of 5b and 6 in dichlorometh-
ane at room temperature (Scheme 2).
The target [2]catenane 7a was obtained in 60% yield following
purification by preparative silica thin layer chromatography and
characterized by 1H, 13C NMR, and ESI-MS. The partial 1H NMR
spectrum of 7a in chloroform is displayed in Figure 2.
As was observed in the pseudorotaxane assembly studies, the
protons of the calix macrocycle component of the catenane in-
O
O
5a
: X = I
vi)
5b: X = Cl
Scheme 1. Reagents and conditions: (i) PFP, DCC, CH2Cl2, 85%; (ii) 2-(4-(2-
azidoethoxy)phenoxy)ethanamine, CH2Cl2, NEt3, 50%; (iii) Pd/C, H2, 100%; (iv)
pyridine-3,5-dicarbonyl dichloride, NEt3, CH2Cl2, 50%; (v) MeI, CH3COCH3, 95%; (vi)
sat NH4Cl(aq), 95%.
To ascertain the ability of calix[4]arene macrobicycle 5b to form
pseudorotaxanes as precursors to the desired catenane, 1H NMR
studies were undertaken with a previously synthesized nitro-
substituted isophthalamide thread 6 (Fig. 1).8 Addition of an
increasing concentration of thread 6 to macrobicycle 5b in CDCl3
produced a number of shifts in the 1H NMR spectra which indi-
cated pseudorotaxane formation. Firstly, significant upfield shifts
of the respective hydroquinone protons of both the thread and
macrocycle were observed. These can be attributed to
pꢀp stack-
ing interactions between the electron-rich hydroquinones and
the complementary electron-deficient pyridinium and nitro-isoph-
thalamide groups of the macrocycle and thread. In addition to
these observations, marked upfield shifts of the protons of the
macrocycle involved in hydrogen bonding to the chloride counter-
ion (Hb and Hc) were evident. These changes are consistent with
the introduction of a competing binding site for chloride, and as
such, protons Hb and H of the thread were seen to move down-
v
field concurrently. Further evidence for pseudorotaxane formation
and the relative orientation of the two components to each other
could be obtained from the comparative downfield shifts of pro-
tons located at the upper rim of the calixarene. Both the amide pro-
tons, He, and those of the aromatic ring involved in the
macrobicycle, Hf, are observed to move downfield, which in
conjunction with the other changes seen can be attributed to
Scheme 2. Reagents and conditions: (i) Grubbs’ second generation catalyst, CH2Cl2,
60%; (ii) AgPF6, CH2Cl2, 90%.

3456
D. E. Phipps, P. D. Beer / Tetrahedron Letters 50 (2009) 3454–3457
δ+δ'
O
O
O
O
O
OEt
O
O
N
O
O HN
N
OEt
H
g
H
α
O
O
O
H
H
O
O
h
O
b
N
Cl
β
H
N
O
χ
O
H
OEt
OEt
a
c
f
N
HN
NH
O
O
O
O
d+d'
Figure 3. Partial 1H NMR spectra (500 MHz, 1:1 CDCl3:CD3OD, 293 K) of (a)
catenane 7b, and (b) 7b and 1 equiv of TBACl.
Table 1
Association constants (K11, Mꢀ1) of 7b with various anions
Aniona
K11
Clꢀ
2050
840
290
160
120
Brꢀ
Figure 2. Partial 1H NMR spectrum (500 MHz, CDCl3, 293 K) of 7a.
ꢀ
H2PO4
AcOꢀ
Fꢀ
volved in hydrogen bonding to the chloride template are signifi-
cantly moved upfield ( d = 0.79 ppm Hb, 0.88 ppm Hc) relative to
the macrocycle 5b. Simultaneously, the hydroquinone protons
Solvent 1:1 CDCl3/CD3OD, 293 K, errors <10%.
D
a
Anions introduced as tetrabutylammonium salts.
0
(Hd+d ) are observed to move upfield and split (
D
d = 0.5 and
0.78 ppm) indicating substantial
the nitro-substituted isophthalamide group. In addition, significant
downfield shifts of the upper-rim calixarene protons
p–p stacking interactions with
high degree of selectivity for chloride in competitive organic sol-
vent mixtures.
(Dd = 0.56 ppm Yf) are consistent with hydrogen-bonding interac-
tions to the nitro group of the thread.
Acknowledgments
Similar but opposing shifts of the thread protons downfield
We would like to thank the EPSRC and GE Healthcare, Amer-
sham for the provision of a CASE-supported studentship (D.E.P.).
(D
d = 1 ppm Hb, 1.74 ppm H ) accompanied by an upfield shift
v
0
and split of the hydroquinone protons (Hd+d ) further corroborate
the changes seen in the pseudorotaxane studies.
ESI-MS evidence for the formation of the catenane was obtained
via observation of a single molecular ion peak at m/z = 1924.7.
Removal of the chloride anion template from the [2]catenane
cavity was achieved via exchange with hexafluorophosphate upon
the addition of AgPF6 to 7a. Confirmation of successful anion ex-
change was obtained via 1H NMR and elemental analysis.
1H NMR anion titration studies of the catenane 7b were under-
taken in a 1:1 CDCl3/CD3OD solvent mixture. Both the para-pyrid-
inium (Hb) and para-nitro (Hb) protons of the catenane were
observed to shift significantly downfield upon addition of chloride
(Fig. 3) while by way of contrast, bromide, fluoride, acetate, and
dihydrogen phosphate anions produced only modest perturba-
tions, suggesting weaker binding.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.02.212.
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