Anion-templated calix[4]arene-based pseudorotaxanes and catenanes

Article abstract of DOI:10.1002/chem.200700041

We present the rational design and anion-binding properties of the first anion-templated pseudorotaxanes and catcnanes in which the "wheel" component is provided by a calix[4|arene macrobicyclic unit. The designs and syntheses of two new calix[4]arene mac

Full text of DOI:10.1002/chem.200700041

FULL PAPER
DOI: 10.1002/chem.200700041
Anion-Templated Calix[4]arene-Based Pseudorotaxanes and Catenanes
Michael D. Lankshear, Nicholas H. Evans, Simon R. Bayly, and Paul D. Beer*[a]
Abstract: We present the rational
design and anion-binding properties of
the first anion-templated pseudorotax-
anes and catenanes in which the
“wheel” component is provided by a
calix[4]arene macrobicyclic unit. The
designs and syntheses of two new cal-
ix[4]arene macrobicycles, 2 and 3, are
presented, and the abilities of these
newspecies both to bind anions and to
undergo anion-dependent pseudorotax-
ane formation are demonstrated. Fur-
thermore, it is shown that performing
ring-closing metathesis reactions on
some of these pseudorotaxane assem-
blies gives novel catenane species 14
and 15, in which the yield of inter-
locked molecule obtained is critically
dependent on the presence of a suit-
G
Keywords: anions
· calixarenes ·
catenanes · self-assembly · supra-
molecular chemistry
Introduction
The calix[4]arene motif has received considerable atten-
tion as a scaffold for the design of numerous receptor sys-
tems, owing to its highly preorganised and readily function-
alised nature.[8] Although examples are much rarer, it has
also been exploited in the formation of interpenetrated and
interlocked species in which the association of the compo-
nents is mediated by hydrogen bonding or cationic templa-
tion effects,[9] whereas the steric bulk of calix[4]arene also
renders it to be used as a stopper in the formation of rotax-
anes.[10] However, as yet, no examples of anion-templated
systems in which the calix[4]arene unit forms part of the
“wheel” component of the interpenetrated species have
been reported. In an effort to address this absence, we
detail herein the first such calix[4]arene-based anion-tem-
plated assemblies.
The generation of novel, topologically complex, interpene-
trated architectures remains a formidable task for the syn-
thetic chemist.[1] The recent emergence of general templa-
tion methodologies based on cationic[2] and neutral[3] motifs
has allowed access to a multitude of highly sophisticated
structures, which in addition to their natural aesthetic
appeal have also begun to be exploited for their potential
molecular-machine-like behaviours.[4] To date, the similar
development and exploitation of strategic anion templation
approaches to these species is markedly less well explored,
probably owing to the inherent challenges associated with
the coordination of anions.[5] Recently, however, approaches
that involve anion-templation methods for the generation of
a range of interpenetrated and interlocked structures have
been elucidated.[6] In particular, our group has shown that
the orthogonal arrangement of two components around a
central halide anion can give rise to pseudorotaxane, rotax-
ane and catenane formations.[7]
The design of these newsystems exploits the established
methodology for the anion-mediated assembly of two com-
ponents. This method involves the association of a charged
pyridinium chloride ion pair and neutral isophthalamide
components in a pseudotetrahedral fashion to yield pseudo-
rotaxane species, which may further be clipped to form cate-
nane derivatives (Scheme 1).[7h,11] The association is aided by
employing secondary forces, namely, p-stacking interactions
and hydrogen bonding. The replacement of the crown ether
portion of previously reported isophthalamide macrocycle 1
with a calix[4]arene moiety yields system 2, which is equally
capable of undergoing anion-mediated threading, but with
greatly increased complexity.
[a] M. D. Lankshear, N. H. Evans, Dr. S. R. Bayly, Prof. P. D. Beer
Inorganic Chemistry Laboratory, Department of Chemistry
University of Oxford, South Parks Road
Oxford, OX1 3QR (UK)
Fax : (+44)1865-272-690
E-mail: paul.beer@chem.ox.ac.uk
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2007, 13, 3861 – 3870
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Scheme 1. General schematic representation for the formation of anion-
templated calix[4]arene pseudorotaxanes and catenanes.
Scheme 2. Preparation of “arm” precursor 4. a) TosCl, NEt3, DMAP
(cat.), THF, 16 h; b) KNPhth, DMF, 1008C, 16 h; c) TosCl, NEt3, DMAP
(cat.), CH2Cl2, 16 h.
Scheme 3. p-tert-Butyl calix[4]arene was heated at reflux
with precursor 4 and potassium carbonate in dry acetonitrile
for four days to give compound 7 in 75% yield after an
aqueous workup was performed. The phthalimide units of 7
were then cleaved to give amine 8 in 98% yield by heating
the reaction mixture at reflux with hydrazine in ethanol for
16 h. Amine 8 was treated under high dilution conditions
with an appropriate bis(acid chloride) and triethylamine in
dry dichloromethane to give target compounds 2 and 3 in 77
and 44% yields, respectively. Only the [1+1] condensation
products were obtained, which were verified by mass spec-
trometric analyses of the reaction mixtures. These processes
represent remarkably facile syntheses of such highly func-
tional macrobicycle derivatives.
This article provides a description of the syntheses of
macrocycle 2 and related macrocycle 3, their anion-binding
properties and their propensities to form anion-templated
pseudorotaxanes. We also showthat such macrocycles may
provide the basis for catenane formation, in which the yield
of the catenane product is dependent on the nature of the
anion template. Furthermore, the anion-binding properties
of one of the resulting catenanes depends on the formation
of a hydrogen-bond-donating pocket by interlocking the two
components.
Anion-binding properties of calix[4]arene macrobicycles 2
and 3: To demonstrate the efficacy of chloride as a template
for the formation of interpenetrated assemblies, the anion-
1
binding properties of 2 and 3 were investigated by H NMR
spectroscopy of solutions in [D6]acetone at 298 K. Unsur-
prisingly, the isophthalamide clefts of these macrobicycles
strongly bind halides in 1:1 stoichiometry, which can be seen
1
by large downfield shifts in the H NMR spectrum for the
isophthalamide (c, d) and hydroquinone (g) protons on ad-
dition of TBA salts (Figure 1a), as expected from the numer-
ous literature studies into this motif.[12] Notably, the signal
that corresponds to hydroxyl proton k is not affected by the
addition of TBA salts. Association constants were derived
by using the WinEQNMR program[13] (Table 1) from results
obtained by monitoring the change in chemical shift of the
signal that arises from the amide protons (d) of the macro-
cycles, which demonstrated that the selectivity order was
ClÀ >BrÀ >IÀ. Again this trend was as expected, and con-
firmed the use of chloride as the anion of choice in the for-
mation of interpenetrated species. Although both macrobi-
cycles also bound acetate strongly, this anion is less suitable
for putative interpenetration because it lacks the spherical
symmetry necessary to mediate the threading process. Fur-
thermore, it is clear that 3 binds anions more strongly than 2
because the nitro group increases the acidity of the amide
groups.
Results and Discussion
Syntheses of calix[4]arene macrobicycles 2 and 3: To pre-
pare these newmacrobicycles, it was first necessary to pre-
pare “arm” precursor 4 (Scheme 2). Commercially available
hydroquinone bis(2-hydroxyethyl)ether was statistically
monotosylated by treating it with a stoichiometric quantity
of tosyl chloride (TosCl) in THF to give 5 in 45% yield.
Compound
5 was treated with potassium phthalimide
(KNPhth) in dry DMF at 1008C to give 6 in 64% yield,
which was subsequently tosylated under standard conditions
(catalytic DMAP, tosyl chloride and triethylamine) to give 4
in 97% yield.
The syntheses of macrobicycles 2 and 3 were then accom-
plished by employing the three-step procedure illustrated in
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Anion-Templated Self-Assembly
FULL PAPER
Scheme 3. Preparations of calix[4]arene macrocycles 2 and 3. a) K2CO3, CH3CN, D, 4 d; b) N2H4, EtOH, D, 16 h; c) NEt3, CH2Cl2, 16 h.
Scheme 4. Formation of anion-templated [2]pseudorotaxanes 2·9a–d and
3·9a–d, in [D6]acetone at 298 K.
Figure 1. 1H NMR spectral changes observed for 2 induced on addition of
TBACl or 9a. a) 2·TBACl, b) 2, c) 2·9a and d) 2+2.5 equiv of 9a. Sol-
vent: [D6]acetone, 298 K.
298 K.[7f] The existence of the desired interpenetrated spe-
cies 2·9a could be inferred from chemical shift data. Fig-
ure 1b and c illustrates the differences in the spectra of 2
and 2·9a, in which a downfield shift in the amide and iso-
phthalyl proton signals (c, d) occurs to indicate that there is
primary coordination to the chloride anion. The spectra also
showupfield shifts in the signals that arise from the hydroxy
(k) and hydroquinone (g, h) protons, which confirms the in-
terpenetrated nature of the products through the presence
of secondary hydrogen-bonding and p-stacking interactions.
Notably, this upfield shift of the hydroquinone protons is in
sharp contrast to the downfield shift that is observed when
TBA chloride is added to receptor 2, as is the upfield shift
in the hydroxyl proton signal. Similar changes were ob-
Table 1. Anion-binding properties of macrobicycles 2 and 3.[a]
2
3
Anion
DdNH [ppm][b]
Ka [mÀ1
]
DdNH [ppm][b]
Ka [mÀ1
]
ClÀ
1.45
0.69
0.10
1.51
0.21
5700
930
1.84
1.11
0.25
2.72
0.48
>104
7600
380
BrÀ
IÀ
90[c]
4000
370
AcOÀ
HSO4
>104
1700
À
[a] Ka (mÀ1) 1:1 binding. Solvent: [D6]acetone, 298 K. Association con-
stant errors <10%. [b] Chemical shift change of the amide proton signal
that occurs on addition of TBA salt (one equiv). [c] Association constant
derived from monitoring isophthalamide proton c.
1
served in the H NMR spectrum of 3 upon the addition of
thread species 9a–d. The stoichiometries of these interac-
tions were 1:1 and association constants for the assembly
process could be inferred by monitoring the dependence of
the pertinent proton chemical shifts of the macrocycles on
the concentration of 9a–d added (Table 2).[13] No discernible
evidence for the formation of 2·9d or 3·9d was obtained,
Formation of anion-templated pseudorotaxanes: The forma-
tion of pseudorotaxane derivatives based on the inclusion of
the simple dihexyl pyridinium threads 9a–d in the macrocy-
clic clefts of 2 and 3 (Scheme 4) was then investigated by
1H NMR spectroscopy of solutions in [D6]acetone at
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P. D. Beer et al.
Table 2. [2]Pseudorotaxane association constants for 2 and 3 with threads
9a–d.[a]
Macrocycle
9a
9b
9c
9d
[b]
2
3
170
240
30
70
<5
20
–
–
[b]
[a] Ka
(mÀ1). Solvent: [D6]acetone, 298 K. Association constant errors
G
<10%. Constants are derived by monitoring the chemical shift of hy-
droxyl proton k. [b] No interaction could be inferred.
which emphasised the importance of the templating anion in
the threading process.
Scheme 5. Alternative route to precursors 10a–d. a) 2-Allyloxyethanol-p-
toluene sulfonate, K2CO3, EtOH, D, 16 h; b) BrCH2CN, K2CO3, acetone,
D, 16 h; c) LiAlH4, Et2O, D, 1 h.
The importance of the anion template in mediating pseu-
dorotaxane assembly is underscored by the magnitudes of
the association constants obtained. Thus, for both 2 and 3
the association is strongest when the counterion is chloride
(9a) and weakest for hexafluorophosphate (9d). The ther-
modynamic stabilities of the pseudorotaxane assemblies
based on bromide (9b) and iodide (9c) lie intermediate be-
tween these two extremes. Thus, the strength of the interac-
tion is dependent on the size, basicity and shape of the
anionic template. Furthermore, the nature of the anion-
binding cleft of the macrobicycle is important because the
strength of pseudorotaxane formation is enhanced by the
presence of the nitro functionality in 3 relative to 2. As in
the case of simple anion binding, this functionality increases
the acidity of the amide hydrogen-bond-donating groups of
the macrobicycle, and thus, enhances the association of the
anion, and in this case also the thread, component.
heating the reactants at reflux in ethanol in the presence of
potassium carbonate to give 11 in 89% yield. This mono-
functionalised material was then treated with bromoacetoni-
trile and potassium carbonate in acetone and heated at
reflux to give 12 in 85% yield. Amine precursor 13 could
then be obtained by reducing 12 with lithium aluminium hy-
dride in ether by heating at reflux. Precursor 13 was further
modified by following known procedures[7i] to give the pyri-
dinium salts 10a–d. This newprocedure makes the prepara-
tion of similar precursors substantially more accessible, and
improves the facility of this general anion-templation strat-
egy.
The formation of [2]pseudorotaxanes 2·10a and 3·10a in
CD2Cl2 was shown by 1H NMR spectroscopic experiments
that are analogous to those used for 2·9a. Again, there was
no evidence for the formation of hexafluorophosphate-di-
rected pseudorotaxanes 2·10d and 3·10d from these experi-
ments, which indicates that an analogous anion-templation
effect was operating in these systems. These pseudorotaxane
precursors were shown to exist, and ring-closing metathesis
reactions were carried out on a solution of 2 with thread
10a in CH2Cl2 in the presence of Grubbsꢁ first-generation
catalyst to give [2]catenane 14a in 29% yield (69% based
on recovered starting material 2) after purification by chro-
matography (Scheme 6). When 10b was used, the yield of
catenane 14b was only 8% and no interlocked product was
obtained for threads 10c and 10d. Pseudorotaxane complex
3·10a was similarly treated to give 15a in 29% yield; the
stronger anion-binding properties of this receptor did not
enhance the yield of catenane obtained. However, no prod-
uct was detected when complex 3·10d was treated in a simi-
lar manner. These observations serve to emphasise the criti-
cal nature of the anion template in mediating the assembly
process, and the yields compare favourably to those ob-
tained for previous systems.[7h]
Formation of anion-templated catenanes: After showing
that the anion-mediated penetration of the simple dihexyl
pyridinium chloride thread 9a into the cavities of 2 and 3
occurred, we then aimed to form permanently interlocked
species, namely, [2]catenanes. Therefore, it was necessary to
form a reactive anion-templated pseudorotaxane complex in
which the terminal functionalities of the incorporated
thread could be joined together, or “clipped” by using ring-
closing metathesis,[11,14] to form the [2]catenane. Catenane
formation could be achieved by the assembly of pseudoro-
taxanes that include the known bisallyl pyridinium chloride
thread 10a within the macrobicycles 2 and 3, followed by
ring-closing metathesis to form the catenanes.[7h] The synthe-
Although mass spectrometric and TLC analysis of the re-
action mixture revealed the presence of a newproduct of
the requisite mass, confirmation of the interlocked nature of
catenane product 14a was obtained from one- and two-di-
mensional NMR experiments (Figures 2 and 3). As in the
case of pseudorotaxane 2·9a, shifts in the primary coordina-
tion spheres of the pyridinium (s, t) and isophthalamide (c,
sis of 10a–d reported previously is somewhat lengthy,[7i] and
therefore, an alternative procedure was devised, the novel
parts of which are summarised briefly in Scheme 5. p-Hy-
droquinone was mono-functionalised with a substoichiomet-
ric quantity of 2-allyloxyethanol-p-toluene sulfonate[15] by
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Anion-Templated Self-Assembly
FULL PAPER
Scheme 6. Synthesis of catenanes 14a–d and 15a. Yields: 14a 29%, 14b
8%, 14c and 14d 0%, 15a 29% and 15d 0%. Catenane 14d was pre-
pared in 75% yield by treatment of 14a with AgPF6.
Figure 3. Portions of the ROESY spectrum of catenane 14a. The spectra
illustrate the coupling interactions between pyridinium H2 proton r and
the calixarene component (top) and the interactions between pyridinium
N-methyl proton q and the calixarene component (bottom). Additional
couplings (7–9) correspond to those to the OCH2 protons of the mole-
cule, which could not be assigned. Solvent: CDCl3 (298 K).
Figure 2. Differences between the 1H NMR spectra of 2, 10a and 14a,
which illustrates the interlocked nature of the catenane product. Solvent:
CDCl3 (298 K).
d) units indicate competitive complexation of the chloride
anion relative to the “free” components. A downfield shift
of the pyridinium methyl proton signal (q), coupled with up-
field shifts in the macrocycle hydroxyl (k) and hydroquinone
(g, h) proton signals, further serves to illustrate the inter-
penetration of the two components. The existence of a mac-
rocyclic thread, rather than the unclosed precursor, is indi-
cated by the disappearance of the signal arising from proton
c’, and the resolution of that arising from b’ owing to the for-
mation of the double bond. In addition, a ROESY NMR
spectrum of 14a indicated that there were coupling interac-
tions between a number of proximal protons, which included
those illustrated in Figure 3.
Catenane anion-binding properties: Exchange of the residu-
al chloride template of 14a with the non-competitive hexa-
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3865

P. D. Beer et al.
fluorophosphate anion by using AgPF6 formed catenane de-
rivative 14d, which contained a topologically unique anion-
binding domain that is defined by the interlocked hydrogen-
bond-donating components.[7,16] Confirmation that species
14d remains interlocked on exchange of the anion was ob-
tained by performing an NOE experiment (Figure 4), in
is able to satisfy the coordination sphere of spherical anions.
Catenane 14d binds the oxoanions acetate and dihydrogen-
phosphate more weakly than halide anions, and less strongly
than 10d binds acetate and dihydrogenphosphate, and inter-
acts strongly with hydrogensulfate. This latter observation is
not easy to explain, but is almost certainly as a result of the
topologically unique binding site provided by interlocking
the two components. Indeed, this selectivity for hydrogen-
sulfate has been previously observed in rotaxane systems by
luminescence spectroscopy techniques.[7e] Thread 10d binds
all of the halides with similar strengths, all of which are
weaker than that of 14d, and shows a preference for binding
bromide. Otherwise, the anion association constants ob-
served correlate well with oxoanion basicity.
These anion-binding results clearly illustrate that the pro-
vision of a unique hydrogen-bond-donating pocket formed
by interlocking the two components in catenane 14d results
in novel anion-binding behaviour. Relative to the free com-
ponents, this anion-binding behaviour manifests as an en-
hancement in affinity for spherical anions, such as the ha-
lides, which allow size and shape complementarity for this
pocket, but a reduction in affinity for the oxoanions acetate
and dihydrogenphosphate. Catenane 14d also demonstrates
selectivity for hydrogensulfate, which must also arise from
the provision of a topologically unique binding pocket.[17]
Figure 4. Results from the NOE experiment performed on N-methylpyri-
dinium proton q in 14d. Top: 1H NMR spectrum of 10d. Bottom: NOE
of proton q in 14d.
Conclusion
which the expected coupling interaction between the pyridi-
nium N-methyl and calixarene macrocycle proton signals
was observed. The nature of the binding domain of 14d was
A newclass of interpenetrated and interlocked motifs that
incorporate a calix[4]arene unit have been successfully as-
sembled by means of a strategic anion-templating method.
The syntheses of these systems represent a significant step
forward in the preparation of anion-templated derivatives,
both in terms of synthetic viability and of their ultimate ap-
plication, such as in molecular sensory devices. It has also
been demonstrated that exchanging the templating chloride
anion of a catenane that contains a calix[4]arene for non-co-
ordinating hexafluorophosphate yields a system that con-
tains a unique anion-binding domain, which is defined by
the interlocked nature of the catenane. This emphasises the
potential use of similar species as sensory devices. The fur-
ther exploitation of such interpenetrated derivatives is cur-
rently a subject of intense interest, because modification of
the highly adaptable calixarene framework will lead to in-
creasingly sophisticated derivatives, the applicability of
which appears to be limited only by the imagination.
1
probed by H NMR spectroscopic titration experiments by
using a CDCl3/CD3OD (1:1) solvent mixture, and compared
with the properties of free macrocycle 2 and thread 10d.[13]
It was found that macrocycle 2 displayed no affinity for
anions in this solvent system, whereas the addition of anions
to 14d induced downfield shifts (0.3–0.5 ppm) in the pyridi-
nium (s) and isophthalyl (c) protons. The amide protons
were not observed in this solvent system owing to exchange
phenomena. The interaction was 1:1 for all of the anions
studied, with the exceptions of acetate and dihydrogensul-
fate in the presence of thread 10d. Monitoring the depen-
A
added allowed association constant data to be derived
(Table 3). These data reveal some interesting trends. Cate-
nane 14d binds halide anions strongly, with a selectivity for
chloride, owing to the provision of a pseudotetrahedral
binding environment by the interlocked components, which
Experimental Section
Table 3. Anion-binding properties of catenane 14d.[a]
À
À
ClÀ
BrÀ
IÀ
AcOÀ
1500[c]
400
H2PO4
1360[c]
480
HSO4
All commercial-grade chemicals were used without further purification.
TBA salts, silver hexafluorophosphate and Grubbs first-generation cata-
lyst were stored prior to use under vacuum in a desiccator that contained
phosphorus pentoxide and self-indicating silica gel. Solvents were dried
by being degassed with nitrogen and then dried by passing them through
a column of activated alumina by using Grubbs apparatus. Elemental
analyses were carried out by the service at the Inorganic Chemistry Lab-
[b]
10d
14d
460
960
590
740
440
550
–
1000
[a] Ka (mÀ1) 1:1 binding. Solvent: CDCl3/CD3OD 1:1, 298 K. Association
constant errors <10%. [b] No association could be inferred. [c] See
ref. [7i]. 1:2 binding observed. Ka
N
A
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Anion-Templated Self-Assembly
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oratory, University of Oxford. Mass spectra were obtained by using a Mi-
cromass LCT (ESMS) instrument. NMR spectra were recorded by using
a Varian Mercury 300, an Oxford Instruments Venus 300 or a Varian
Unity Plus 500 spectrometer, in which the solvent serves as the lock and
internal reference.
Hydroquinone bis(2-hydroxylethyl)ether monotosylate (5): Tosyl chloride
(6.06 g, 31.8 mmol) was added to a stirred solution of hydroquinone
bis(2-hydroxylethyl)ether (6.00 g, 30.3 mmol), triethylamine (5.5 mL,
39.4 mmol) and DMAP (cat. 10 mg) in dry THF (150 mL), and the result-
ing reaction mixture was stirred under a nitrogen atmosphere for 16 h.
The resulting white suspension was filtered, and the filtrate was concen-
trated in vacuo to give a crude yellowmaterial that was purified by silica
gel chromatography (EtOAc/hexane 50:50 v/v) and eluted as the third
band. The fractions were concentrated in vacuo to give 5 as a yellowoil
(4.81 g, 45%). 1H NMR (300 MHz, CDCl3): d=2.46 (s, 3H; CH3), 3.95
(m, 2H; OCH2), 4.03 (m, 2H; OCH2), 4.10 (t, 3J=4.7 Hz, 2H; OCH2),
4.34 (t, 3J=4.7 Hz, 2H; OCH2), 6.73 (d, 3J=9.4 Hz, 2H; ArH), 6.82 (d,
3J=9.4 Hz, 2H; ArH), 7.36 (d, 3J=8.1 Hz, 2H; TosH), 7.82 ppm (d, 3J=
8.1 Hz, 2H; TosH); 13C NMR (75.5 MHz, CDCl3): d=21.64, 61.49, 66.14,
68.21, 69.71, 115.43, 115.69, 127.98, 129.82, 132.77, 144.91, 152.39,
153.22 ppm; ESMS: m/z: 375.08 [M+Na]+.
Isophthalamide calix[4]arene macrobicycle (2): A solution of bis(amine)
T
8 (1.50 g, 1.49 mmol) in dry CH2Cl2 (75 mL) and a solution of isophthalo-
yl dichloride (0.30 g, 1.49 mmol) in dry CH2Cl2 (75 mL) were added drop-
wise, simultaneously, to
a stirred solution of triethylamine (0.5 mL,
3.28 mmol) in dry CH2Cl2 (1200 mL) over a period of 1 h, under an at-
mosphere of nitrogen. The reaction mixture was allowed to stir at room
temperature for a further 16 h, before it was reduced in vacuo to approxi-
mately 100 mL, and this concentrated solution was washed consecutively
with 1m aqueous HCl solution (2”100 mL), H2O (100 mL), 1m aqueous
NaOH solution (100 mL) and brine (100 mL). The organic layer was then
dried over MgSO4, filtered, and the solvent was removed in vacuo. Purifi-
cation was completed by silica gel chromatography (EtOAc/hexane 90:10
v/v) in which the first band that eluted was collected. The combined frac-
tions were concentrated in vacuo to give 2 as a white solid (1.31 g, 77%).
M.p. 242–2448C; 1H NMR (300 MHz, CDCl3): d=1.03 (s, 18H; CH3),
1.29 (s, 18H; CH3), 3.35 (d, 2J=12.9 Hz, 4H; ArCHinHoutAr), 3.83 (m,
4H; NCH2), 4.11 (m, 4H; OCH2), 4.28 (m, 8H; 2”OCH2), 4.43 (d, 2J=
12.9 Hz, 4H; ArCHinHoutAr), 6.83 (m, 8H; hydroq ArH), 6.88 (s, 4H;
calix ArH), 6.99 (brs, 2H, NH), 7.07 (s, 4H; calix ArH), 7.51 (t, 3J=
7.6 Hz, 1H; isoph ArH5), 7.58 (s, 2H; OH), 7.98 (s, 1H; isoph ArH2),
8.03 ppm (d, 2H, 3J=7.6 Hz; isoph ArH4, ArH6); 13C NMR (75.5 MHz,
CDCl3): d=31.06, 31.66, 33.80, 33.97, 39.68, 67.33, 74.07, 116.09, 115.58,
123.39, 125.11, 125.66, 127.87, 129.55, 131.15, 132.83, 134.45, 141.43,
147.04, 149.88, 150.56, 152.76, 153.23, 166.86 ppm; ESMS: m/z: 1159.60
[M+Na]+; elemental analysis calcd (%) for C72H84N2O10: C 76.0, H 7.4,
N 2.5; found: C 75.8, H 7.4, N 2.6.
(2-Hydroxylethoxy)-4-(2-phthalimidoethoxy)benzene
(6):
Potassium
phthalimide (2.60 g, 14.1 mmol) was added to a solution of 5 (3.30 g,
9.38 mmol) in anhydrous DMF (25 mL), and the resulting suspension was
heated to 1008C for 16 h, under a nitrogen atmosphere. The reaction
mixture was subsequently allowed to cool to room temperature and was
then poured onto H2O (100 mL). The resulting milky suspension was ex-
tracted with CH2Cl2 (3”50 mL), before the organic extracts were com-
bined, dried over MgSO4, filtered, and the filtrate concentrated in vacuo.
The product was purified by silica gel chromatography (EtOAc/hexane
50:50 v/v) and eluted as the third band. The fractions were concentrated
in vacuo to give 6 as a white solid (1.96 g, 64%). M.p. 114–1168C;
1H NMR (300 MHz, CDCl3): d=2.04 (t, 3J=6.2 Hz, 1H; OH), 3.93 (m,
2H; CH2OH), 4.03 (m, 2H; CH2CH2OH), 4.09 (m, 2H; CH2), 4.19 (m,
3
4
2H; CH2), 6.82 (m, 4H; ArH), 7.73 (dd, J=5.4, J=3.1 Hz, 2H; PhthH),
7.87 ppm (dd, 3J=5.4, 4J=3.1 Hz, 2H; PhthH); 13C NMR (75.5 MHz,
CDCl3): d=37.34, 61.45, 65.29, 69.70, 115.38, 115.61, 123.28, 131.93,
133.97, 152.67, 152.98, 168.14 ppm; ESMS: m/z calcd for C18H17NO5Na:
350.1004; found: 350.1012 [M+Na]+.
5-Nitroisophthalamide calix[4]arene macrobicycle (3): This compound
was prepared in an analogous manner to macrobicycle 2 by using 5-nitro-
isophthaloyl dichloride (49.2 mg, 0.199 mmol), calix[4]arene amine
8
(200 mg, 0.199 mmol) and triethylamine (0.1 mL, 0.7 mmol) in dry
CH2Cl2 (200 mL total volume). Purification was accomplished by prepa-
rative TLC (silica gel, CH2Cl2/MeOH 65:35 v/v) to give 3 as a bright
yellowsolid (104 mg, 44%). M.p. 234–236 8C; 1H NMR (300 MHz,
CDCl3): d=1.01 (s, 18H; CH3), 1.29 (s, 18H; CH3), 3.34 (d, 2J=12.9 Hz,
4H; ArCHinHoutAr), 3.87 (m, 4H; NCH2), 4.12 (m, 4H; OCH2), 4.30 (m,
8H; 2”OCH2), 4.42 (d, 2J=12.9 Hz, 4H; ArCHinHoutAr), 6.75 (m, 4H;
hydroq ArH), 6.86 (m, 8H; calix ArH, hydroq ArH), 7.07 (s, 4H; calix
ArH), 7.15 (brs, 2H; NH), 7.44 (s, 2H; OH), 8.38 (s, 1H; isoph ArH2),
8.82 ppm (s, 2H; isoph ArH4, ArH6); 13C NMR (75.5 MHz, CDCl3): d=
31.03, 31.66, 33.81, 33.94, 40.13, 67.04, 67.27, 74.22, 115.43, 115.94, 125.13,
125.50, 125.65, 127.91, 129.22, 132.65, 136.08, 141.51, 147.04, 148.69,
149.93, 150.47, 152.28, 153.16, 164.75 ppm; ESMS: m/z: 1204.51 [M+Na]+
5,11,17,23-Tetra-tert-butyl-25,27-di{2-[4-(2-phthalimidoethoxy)phenoxy]-
A
lix[4]arene (0.4 g, 0.56 mmol) and potassium carbonate (0.06 g, 1.2 mmol)
in dry CH3CN (25 mL) was stirred under a nitrogen atmosphere for 1 h.
Compound 4 (0.72 g, 1.5 mmol) was then added and the reaction mixture
heated at reflux under a nitrogen atmosphere for 4 d. The suspension
was then allowed to cool to room temperature, and the solvent was care-
fully removed in vacuo. The resulting off-white residue was triturated
with 1m aqueous HCl solution (50 mL) to give an aqueous suspension
that was extracted with CH2Cl2 (3”50 mL). The combined organic ex-
tracts were washed with H2O (2”50 mL), dried over MgSO4 and filtered.
Removal of the solvent in vacuo gave a crude material that was purified
by silica gel chromatography (EtOAc/hexane 40:60 v/v) and eluted as the
first (intense) band. The fractions were combining and the solvent was
removed in vacuo to give 7 as a white solid (0.50 g, 75%). M.p. 194–
; elemental analysis calcd (%) for C72H83N3O12·3= CH2Cl2: C 70.1, H 6.8,
4
N 3.4; found: C 70.2, H 6.8, N 3.5.
1
1968C; H NMR (300 MHz, CDCl3): d=1.01 (s, 18H; CH3), 1.28 (s, 18H;
(2-Tosyloxyethoxy)-4-(2-phthalimidoethoxy)benzene (4): Triethylamine
(2 mL, 14.2 mmol) and DMAP (cat. 10 mg) were added to a solution of 6
(1.22 g, 3.73 mmol) and tosyl chloride (0.78 g, 4.10 mmol) in dry CH2Cl2
(50 mL), and the reaction mixture was then stirred under a nitrogen at-
mosphere for 16 h. H2O (25 mL) was added to the solution, and the vigo-
rously stirred biphasic mixture was then carefully neutralised with 10%
aqueous citric acid solution. The phases were then separated, and the or-
ganic layer was subsequently washed with H2O (2”25 mL) and brine
(50 mL), before it was dried over MgSO4 and filtered. Subsequent remov-
al of the solvent in vacuo gave 4 as a white solid (1.74 g, 97%). M.p. 123–
1258C; 1H NMR (300 MHz, CDCl3): d=2.44 (s, 3H; CH3), 4.07 (m, 4H;
2”CH2), 4.17 (m, 2H; CH2), 4.32 (t, 3J=4.7 Hz, 2H; CH2), 6.66 (d, 3J=
9.4 Hz, 2H; ArH), 6.77 (d, 3J=9.4 Hz, 2H; ArH), 7.33 (d, 3J=8.0 Hz,
2H; TosH), 7.73 (dd, 3J=5.4, 4J=3.1 Hz, 2H; PhthH), 7.80 (d, 3J=
8.0 Hz, 2H; TosH), 7.87 ppm (dd, 3J=5.4, 4J=3.1 Hz, 2H; PhthH);
13C NMR (75.5 MHz, CDCl3): d=21.61, 37.33, 65.27, 66.05, 68.18, 115.55,
123.29, 127.95, 129.79, 131.94, 132.77, 134.01, 144.87, 152.35, 152.89,
154.49, 168.13 ppm. ESMS: m/z calcd for C25H23NO7SNa: 504.1093;
found: 504.1089 [M+Na]+.
CH3), 3.30 (d, 2J=12.9 Hz, 4H; ArCHinHoutAr), 4.09 (m, 4H; CH2), 4.19
(m, 8H; 2”CH2), 4.26 (m, 4H; CH2), 4.40 (d, 2J=12.9 Hz, 4H; Ar-
CHinHoutAr), 6.81 (m, 8H; hydroq ArH), 6.86 (s, 4H; calix ArH), 7.04 (s,
4H; calix ArH), 7.59 (s, 2H; OH), 7.66 (dd, 3J=5.4, 4J=3.1 Hz, 2H;
PhthH), 7.83 ppm (dd, 3J=5.4, 4J=3.1 Hz, 2H; PhthH); 13C NMR
(75.5 MHz, CDCl3): d=31.03, 31.65, 33.77, 33.91, 37.43, 65.31, 67.16,
73.97, 115.52, 123.26, 125.57, 127.76, 131.96, 132.85, 133.97, 141.19, 146.83,
149.79, 150.61, 153.04, 168.15 ppm; ESMS: m/z: 1289.52 [M+Na]+.
5,11,17,23-Tetra-tert-butyl-25,27-di{2-[4-(2-aminoethoxy)phenoxy]eth-
A
was dissolved in ethanol (50 mL) before hydrazine monohydrate (1 mL,
excess) was added, and the stirred solution was heated at reflux for 16 h.
After the reaction mixture was allowed to cool to room temperature, it
was added to H2O (100 mL) and then extracted by using EtOAc (4”
50 mL). The combined organic layers were dried over MgSO4, filtered
and solvent removed in vacuo to give 8 as a white solid (0.81 g, 98%).
M.p. 205–2078C; 1H NMR (300 MHz, CDCl3): d=1.03 (s, 18H; CH3),
1.28 (s, 18H; CH3), 3.07 (m, 4H; CH2N), 3.31 (d, 2J=12.9 Hz, 4H; Ar-
Chem. Eur. J. 2007, 13, 3861 – 3870
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3867

P. D. Beer et al.
CHinHoutAr), 3.94 (t, 3J=5.0 Hz, 4H; CH2CH2N), 4.28 (m, 8H; 2”
OCH2), 4.41 (d, 2J=12.9 Hz, 4H; ArCHinHoutAr), 6.83 (d, 3J=8.8 Hz,
4H; hydroq ArH), 6.87 (s, 4H; calix ArH), 6.90 (d, 3J=8.8 Hz, 4H;
hydroq ArH), 7.05 (s, 4H; calix ArH), 7.56 ppm (s, 2H; OH); 13C NMR
(75.5 MHz, CDCl3): d=31.06, 31.66, 33.78, 33.95, 41.63, 67.22, 70.65,
73.97, 115.33, 115.96, 125.05, 125.60, 127.81, 132.86, 141.25, 146.87, 149.82,
150.59, 152.89, 153.23 ppm; ESMS: m/z: 1007.55 [M+H]+.
ArCHinHoutAr), 3.57 (m, 4H; CH2), 3.73 (m, 4H; CH2), 3.79 (m, 4H;
CH2), 3.85 (m, 4H; CH2), 4.08 (m, 16H; CH2CHCHCH2, 3”CH2), 4.15
(m, 4H, CH2), 4.42 (d, 2J=13.3 Hz, 4H; ArCHinHoutAr), 4.94 (s, 3H; N+
CH3), 5.66 (s, 2H; OH), 5.84 (s, 2H; CH2CHCHCH2), 6.19 (m, 4H;
calix-hydroq ArH), 6.31 (m, 4H; calix-hydroq ArH), 6.68 (s, 4H, calix
ArH), 6.76 (m, 8H; py-hydroq ArH), 7.21 (s, 4H; calix ArH), 7.59 (t,
3J=7.6 Hz, 1H; isoph ArH5), 8.27 (d, 3J=7.6 Hz, 2H; isoph ArH4,
ArH6), 8.71 (brs, 4H; 2”CONH), 8.99 (s, 2H; pyH2, H6), 9.23 (s, 1H;
isoph ArH2), 9.90 ppm (s, 1H; pyH4); 13C NMR (75.5 MHz, CDCl3): d=
30.89, 31.75, 34.03, 39.92, 41.33, 50.84, 65.13, 66.36, 66.76, 67.53, 68.32,
68.67, 70.62, 71.21, 75.22, 109.97, 113.88, 114.70, 115.93, 124.09, 125.53,
125.91, 128.41, 129.00, 129.37, 131.51, 131.93, 133.50, 133.69, 142.77,
144.37, 147.51, 149.98, 150.46, 151.57, 152.63, 152.80, 153.80, 159.72,
166.80 ppm; ESMS: m/z: 1729.81 [MÀCl]+; elemental analysis calcd (%)
for C104H122ClN5O18·CH2Cl2: C 68.2, H 6.8, N 3.8; found: C 68.3, H 7.0, N
3.5.
4-[2-(Allyloxy)ethoxy]phenol (11): 2-Allyloxyethanol-p-toluene sulfonate
(13.09 g, 0.051 mol), p-hydroquinone (22.55 g, 0.204 mol) and potassium
carbonate (7.76 g, 0.056 mol) were suspended in ethanol (350 mL) and
heated at reflux for 18 h under a nitrogen atmosphere. The reaction mix-
ture was allowed to cool to room temperature, filtered, and the solvent
was removed in vacuo. The residue was then redissolved in H2O
(100 mL) and acidified to pH 3 by the addition of 1m aqueous HCl solu-
tion. The crude product was extracted with CHCl3 (3”100 mL), before
the combined organic extracts were dried over MgSO4, filtered, and the
solvent removed in vacuo. Purification of this crude product by silica gel
Isophthalamide calix[4]arene catenane bromide (14b): This compound
was prepared in an analogous method to that used for the formation of
14a by using macrocycle 2 (100.0 mg, 0.0879 mmol), bromide thread 10b
(92.4 mg, 0.132 mmol) and Grubbs first-generation catalyst (19 mg, 20%
by mass). After an identical workup to that used to prepare 14a, product
14b was isolated as a pale yellow solid (13 mg, 8% or 42% including re-
covered starting material 2). 1H NMR (300 MHz, CDCl3): d=0.87 (s,
chromatography (hexane/EtOAc 60:40 v/v) gave 11 as
a brown oil
(8.83 g, 89%). 1H NMR (300 MHz, CDCl3): d=3.80 (m, 2H, Ar-
OCH2CH2), 4.09 (m, 4H, OCH2CHCH2, ArOCH2), 5.20–5.34 (m, 2H,
OCH2CHCH2), 5.69 (brs, 1H; OH), 5.88–6.01 (m, 1H; OCH2CHCH2),
6.75 ppm (m, 4H; hydroq ArH); 13C NMR (75.5 MHz, CDCl3): d=67.96,
68.96, 72.36, 115.72, 116.01, 117.72, 134.22, 149.82, 152.55 ppm; ESMS: m/
z: 217.08 [M+Na]+.
18H; C
N
N
2-{4-[2-(Allyloxy)ethoxy]phenoxy}acetonitrile (12): Compound 11 (2.05 g,
10.6 mmol) was dissolved in acetone (50 mL) before bromoacetonitrile
(1.39 g, 11.6 mmol) and potassium carbonate (1.60 g, 11.6 mmol) were
added, and the reaction mixture was heated at reflux for 16 h under a ni-
trogen atmosphere. The suspension was then allowed to cool to room
temperature, filtered, and the filtrate was concentrated in vacuo. The re-
sulting brown oil was dissolved in CHCl3 and filtered through a plug of
silica gel. Removal of solvent from the filtrate in vacuo yielded 12 as a
yellowoil (2.10 g, 85%). 1H NMR (300 MHz, CDCl3): d=3.78 (t, 3J=
4.7 Hz, 2H; ArOCH2CH2), 4.09 (m, 4H; OCH2CHCH2, ArOCH2), 4.69
(s, 2H; NCCH2) 5.20–5.34 (m, 2H; OCH2CHCH2), 5.88–6.01 (m, 1H;
OCH2CHCH2), 6.91 ppm (m, 4H; hydroq ArH); 13C NMR (75.5 MHz,
CDCl3): d=54.67, 67.83, 68.35, 72.21, 115.62, 116.44, 117.28, 134.37,
150.65, 154.63 ppm; ESMS: m/z calcd for C13H16NO3: 234.1140; found:
234.1130 [M+H]+.
CHinHoutAr), 3.58 (m, 4H; CH2), 3.73 (m, 4H; CH2), 3.80 (m, 4H; CH2),
3.86 (m, 4H; CH2), 4.05–4.15 (m, 20H; CH2CHCHCH2, 4”CH2), 4.42 (d,
2J=13.6 Hz, 4H; ArCHinHoutAr), 4.94 (s, 3H; N+CH3), 5.66 (s, 2H; OH),
5.84 (s, 2H; CH2CHCHCH2), 6.22 (m, 4H; calix-hydroq ArH), 6.32 (m,
4H; calix-hydroq ArH), 6.67 (s, 4H; calix ArH), 6.74 (m, 8H; py-hydroq
3
ArH), 7.21 (s, 4H; calix ArH), 7.59 (t, J=7.6 Hz, 1H; isoph ArH5), 8.26
(d, 3J=7.6 Hz, 2H; isoph ArH4, ArH6), 8.69 (brs, 4H; 2”NH), 8.99 (s,
2H; pyH2, H6), 9.22 (s, 1H; isoph ArH2), 9.92 ppm (s, 1H; pyH4);
13C NMR (75.5 MHz, CDCl3): d=30.89, 31.74, 33.84, 39.99, 66.23, 66.76,
67.52, 68.30, 68.72, 69.96, 71.18, 75.24, 109.97, 113.98, 114.74, 115.85,
116.16, 124.17, 125.53, 125.89, 128.39, 128.99, 129.31, 131.51, 131.94,
133.52, 142.75, 144.48, 147.48, 149.95, 150.42, 151.56, 152.60, 152.82,
161.91, 166.84 ppm; ESMS: m/z: 1729.85 [MÀBr]+; elemental analysis
calcd (%) for C104H122N5O18Br·2= CH2Cl2: C 67.4, H 6.7, N 3.8; found: C
3
67.1, H 6.9, N 3.7.
2-{4-[2-(Allyloxy)ethoxy]phenoxy}ethylamine (13):
A solution of 12
Isophthalamide calix[4]arene catenane hexafluorophosphate (14d): Chlo-
ride catenane 14a (73 mg, 0.0413 mmol) was dissolved in dry CH2Cl2
(100 mL) and stirred with AgPF6 (52 mg, 0.207 mmol) for 2 h under a ni-
trogen atmosphere in the absence of light. The suspension was then fil-
tered, and the brown solid obtained was triturated with CH3CN. This
mixture was then filtered and the yellow filtrate concentrated in vacuo.
The solid obtained was then redissolved in CH2Cl2 (30 mL) and vigorous-
ly stirred with H2O (30 mL) for 15 min. The organic layer was separated,
dried over MgSO4, filtered and the solvent removed in vacuo to give 14d
(3.75 g, 16.0 mmol) in dry diethyl ether (50 mL) was slowly added to a
suspension of LiAlH4 (0.92 g, 24.1 mmol) in dry diethyl ether (250 mL),
and the resulting suspension was then heated at reflux, under a nitrogen
atmosphere, for 1 h. The reaction mixture was subsequently allowed to
cool to room temperature, and unreacted LiAlH4 was neutralised by the
careful addition of 10% aqueous NaOH solution (40 mL). H2O (100 mL)
was then added, and the phases separated. The diethyl ether layer was
then decanted, and the remaining aqueous layer extracted by using dieth-
yl ether (8”100 mL). The organic layers were combined, dried over
MgSO4, filtered and the filtrate was concentrated in vacuo to give 13 as a
red-brown oil (3.47 g, 91%). 1H NMR (300 MHz, CDCl3): d=1.50 (brs,
2H; NH2), 3.04 (t, 3J=5.1 Hz, 2H; CH2NH2), 3.77 (m, 2H; OCH2), 3.93
(t, 3J=5.1 Hz, 2H; CH2CH2N), 4.08 (m, 4H; 2”OCH2), 5.18–5.34 (m,
2H; OCH2CHCH2), 5.88–6.01 (m, 1H; OCH2CHCH2), 6.84 ppm (m, 4H;
hydroq ArH); 13C NMR (75.5 MHz, CDCl3): d=41.60, 67.98, 68.53,
70.65, 72.29, 115.27, 115.54, 117.28, 134.50, 152.98, 153.11 ppm; ESMS:
m/z calcd for C13H20NO3: 238.1443; found: 238.1432 [M+H]+.
as a bright yellowsolid (58 mg, 75%). 1H NMR (300 MHz, CDCl3): d=
2
0.85 (s, 18H; C
(CH3)3), 1.39 (s, 18H; C
G
ArCHinHoutAr), 3.61–3.73 (m, 16H; 4”CH2), 3.90 (m, 4H; CH2), 4.01 (m,
8H; CH2CHCHCH2, CH2), 4.12 (m, 8H; 2”CH2), 4.46 (d, 2J=13.7 Hz,
4H; ArCHinHoutAr), 4.78 (s, 3H; N+CH3), 5.82 (s, 2H; CH2CHCHCH2,
cis 26%), 5.82 (s, 2H; CH2CHCHCH2, trans 74%), 6.27 (m, 6H; calix-
hydroq ArH, OH), 6.38 (m, 4H; calix-hydroq ArH), 6.64 (m, 12H; calix
ArH, py-hydroq ArH), 7.21 (s, 4H; calix ArH), 7.44 (brs, 2H; CONH),
3
3
7.64 (t, J=7.7 Hz, 1H; isoph ArH5), 7.83 (brs, 2H; CONH), 8.13 (d, J=
7.6 Hz, 2H; isoph ArH4, ArH6), 8.70 (s, 1H; isoph ArH2), 8.77 ppm (s,
3H; pyH); 13C NMR (75.5 MHz, CDCl3): d=26.05, 30.91, 31.73, 33.81,
33.97, 39.98, 40.70, 50.22, 65.49, 66.68, 66.95, 68.14, 69.04, 71.02, 75.10,
114.85, 114.17, 115.44, 115.74, 125.61, 125.72, 128.31, 128.97, 129.25,
131.11, 131.52, 133.52, 134.04, 142.58, 143.83, 147.22, 149.91, 150.06,
151.74, 152.43, 152.69, 152.96, 160.58, 167.08 ppm. 19F NMR (282.4 MHz,
Isophthalamide calix[4]arene catenane chloride (14a): Macrobicycle 2
(100.0 mg, 0.0879 mmol) and chloride thread 10a (86.8 mg, 0.132 mmol)
were dissolved in dry CH2Cl2 (65 mL) and stirred for 20 minutes. Grubbs
first-generation catalyst (17 mg, 20% by mass) was added, and the reac-
tion mixture was stirred for 16 h under an atmosphere of nitrogen. The
solvent was then removed in vacuo to give the crude material, which was
purified by preparative TLC (silica gel, CH2Cl2/MeOH 96:4 v/v) to give
impure catenane 14a. Trituration of this product in diisopropyl ether
gave the pure catenane as a pale yellowsolid (45 mg, 29% or 69% in-
CDCl3): d=À70.90 ppm (d, J=715 Hz, 6F; PF6À). 31P NMR (121.5 MHz,
1
CDCl3): d=156.45 ppm (septet, 1J=715 Hz, 1P; PF6À); ESMS: m/z:
[MÀPF6]+;
elemental
analysis
calcd
(%)
for
cluding recovered starting material 2). 1H NMR (300 MHz, CDCl3): d=
1729.87
2
0.87 (s, 18H; C
(CH3)3), 1.40 (s, 18H; C
G
C104H122N5O18PF6·5H2O: C 63.6, H 6.8, N 3.6; found C 63.3, H 6.8, N 3.3.
3868
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 3861 – 3870

Anion-Templated Self-Assembly
FULL PAPER
5-Nitroisophthalamide calix[4]arene catenane chloride (15a): This com-
pound was prepared in an analogous method to that used to form chlo-
ride catenane 14a by using nitro calix[4]arene macrocycle 3 (93 mg,
0.0786 mmol), chloride thread 10a (77 mg, 0.0118 mmol) and Grubbs
first-generation catalyst (17 mg, 20% by mass). The solvent system used
for the preparative TLC was 95:5 v/v CH2Cl2/MeOH. The pure product
was isolated as a pale yellow solid (41 mg, 29% or 61% from recovered
starting material 3). 1H NMR (500 MHz, CDCl3): d=0.84 (s, 18H; C-
Raymo, J. F. Stoddart, Angew. Chem. 2000, 112, 3484–3530; Angew.
Chem. Int. Ed. 2000, 39, 3348–3391.
[5] a) J. L. Sessler, P. A. Gale, W.-S. Cho, Anion Receptor Chemistry,
RSC, Cambridge, 2006; b) P. A. Gale, R. Quesada, Coord. Chem.
Rev. 2006, 250, 3219–3244; c) K. Bowman-James, Acc. Chem. Res.
2005, 38, 671–678; d) P. A. Gale, Coord. Chem. Rev. 2003, 240, 191;
e) P. D. Beer, P. A. Gale, Angew. Chem. 2001, 113, 502–532; Angew.
Chem. Int. Ed. 2001, 40, 486–516; f) Supramolecular Chemistry of
Anions (Eds.: A. Bianchi, K. Bowman-James, E. García-EspaÇa),
Wiley-VCH, NewYork, 1997.
[6] a) M. D. Lankshear, P. D. Beer, Coord. Chem. Rev. 2006, 250, 3142–
3160; b) N. Gimeno, R. Vilar, Coord. Chem. Rev. 2006, 250, 3161–
3189; c) P. D. Beer, M. R. Sambrook, in Encyclopedia of Nano-
science and Nanotechnology (Eds.: J. A. Schwarz, C. I. Contescu, K.
Putyera), Dekker, NewYork, 2004, pp. 69–81; d) L. S. Evans, P. A.
Gale, in Encyclopedia of Nanoscience and Nanotechnology (Eds.:
J. A. Schwarz, C. I. Contescu, K. Putyera), Dekker, New York, 2004,
pp. 55–68; e) R. Vilar, Angew. Chem. 2003, 115, 1498–1516; Angew.
Chem. Int. Ed. 2003, 42, 1461–1477; f) C. A. Schalley, G. Silva, C. F.
Nising, P. Linnartz, Helv. Chim. Acta 2002, 85, 1578–1596; g) J. M.
Mahoney, R. Shukla, R. A. Marshall, A. M. Beatty, J. Zajicek, B. D.
Smith, J. Org. Chem. 2002, 67, 1436–1440; h) G. M. Hübner, J.
Glꢂser, C. Seel, F. Vçgtle, Angew. Chem. 1999, 111, 395–398;
Angew. Chem. Int. Ed. 1999, 38, 383–386; i) M. C. T. Fyfe, S. K.
Hickingbottom, S. Menzer, J. F. Stoddart, A. J. P. White, D. J. Wil-
liams, Chem. Eur. J. 1998, 4, 577–589.
[7] a) P. D. Beer, M. R. Sambrook, D. Curiel, Chem. Commun. 2006,
2105–2117; b) M. R. Sambrook, D. Curiel, E. J. Hayes, P. D. Beer,
S. J. Pope, S. Faulkner, New J. Chem. 2006, 30, 1133–1136; c) K.-Y.
Ng, A. R. Cowley, P. D. Beer, Chem. Commun. 2006, 3676–3678;
d) M. R. Sambrook, P. D. Beer, M. D. Lankshear, R. F. Ludlow, J. A.
Wisner, Org. Biomol. Chem. 2006, 4, 1529–1538; e) D. Curiel, P. D.
Beer, Chem. Commun. 2005, 1909–1911; f) M. R. Sambrook, P. D.
Beer, J. A. Wisner, R. L. Paul, A. R. Cowley, F. Szemes, M. G. B.
Drew, J. Am. Chem. Soc. 2005, 127, 2292–2302; g) D. Curiel, P. D.
Beer, R. L. Paul, A. R. Cowley, M. R. Sambrook, F. Szemes, Chem.
Commun. 2004, 1162–1163; h) M. R. Sambrook, P. D. Beer, J. A.
Wisner, R. L. Paul, A. R. Cowley, J. Am. Chem. Soc. 2004, 126,
15364–15365; i) J. A. Wisner, P. D. Beer, M. G. B. Drew, M. R. Sam-
brook, J. Am. Chem. Soc. 2002, 124, 12469–12476; j) J. A. Wisner,
P. D. Beer, N. G. Berry, B. Tomapatanaget, Proc. Natl. Acad. Sci.
USA 2002, 99, 4983–4986; k) J. A. Wisner, P. D. Beer, M. G. B.
Drew, Angew. Chem. 2001, 113, 3718–3721; Angew. Chem. Int. Ed.
2001, 40, 3606–3609.
A
C
(CH3)3), 3.46 (d, 2J=13.6 Hz, 4H; Ar-
N
CHinHoutAr), 4.10–4.16 (brm, 32H; 8”CH2), 3.76 (m, 4H; CH2), 4.40 (d,
2J=13.6 Hz, 4H; ArCHinHoutAr), 4.94 (s, 3H; N+CH3), 5.62 (s, 2H; OH),
5.73 (s, 2H; CH2CHCHCH2 cis 13%), 5.94 (s, 2H; CH2CHCHCH2 trans
87%), 6.22 (m, 4H; calix-hydroq ArH), 6.37 (m, 4H; calix-hydroq ArH),
6.68 (m, 8H; calix ArH, py-hydroq ArH), 6.78 (m, 4H; py-hydroq ArH),
7.22 (s, 4H; calix ArH), 8.70 (s, 2H; isoph ArH4, ArH6), 8.75–8.95 (brs,
4H; 2”NH), 9.00 (s, 2H; pyH2, H6), 9.65 (s, 1H; isoph ArH2), 9.92 (s,
1H; pyH4). ESMS m/z: 1774.64 [MÀCl]+; elemental analysis calcd (%)
for C104H121N6O20·1= CH2Cl2: C 66.1, H 6.5, N 4.4; found: C 66.1, H 6.6, N
2
4.4.
Acknowledgements
We wish to thank GE Healthcare and the EPSRC for a CASE supported
studentship (MDL) and a post-doctoral fellowship (SRB). We are also
grateful for the contribution of Dr. Nick Rees (Oxford) to the 2D-NMR
studies involved in this work.
[1] a) F. Aricó, J. D. Badjic, S. J. Cantrill, A. H. Flood, K. C.-F. Leung,
Y. Liu, J. F. Stoddart, Top. Curr. Chem. 2005, 249, 203–259; b) T. J.
Hubin, D. H. Busch, Coord. Chem. Rev. 2000, 200–202, 5–52;
c) G. A. Breault, C. A. Hunter, P. C. Mayers, Tetrahedron 1999, 55,
5265–5293; d) F. M. Raymo, J. F. Stoddart, Chem. Rev. 1999, 99,
1643–1664; e) Molecular Catenanes, Rotaxanes and Knots: A Jour-
ney Through the World of Molecular Topology (Eds.: J.-P. Sauvage,
C. Dietrich-Buchecker), Wiley-VCH, Weinheim, 1999.
[2] a) S. J. Loeb, J. Tiburcio, S. J. Vella, J. A. Wisner, Org. Biomol.
Chem. 2006, 4, 667–680; b) A.-M. Fuller, D. A. Leigh, P. J. Lusby,
I. D. H. Oswald, S. Parsons, D. B. Walker, Angew. Chem. 2004, 116,
4004–4008; Angew. Chem. Int. Ed. 2004, 43, 3914–3918; c) K. S.
Chichak, S. J. Cantrill, A. R. Pease, S.-H. Chiu, G. W. V. Cave, J. L.
Atwood, J. F. Stoddart, Science 2004, 304, 1308–1312; d) D. A.
Leigh, P. J. Lusby, S. J. Teat, A. J. Wilson, J. K. Y. Wong, Angew.
Chem. 2001, 113, 1586–1591; Angew. Chem. Int. Ed. 2001, 40, 1538–
1543; e) A. G. Kolchinski, R. A. Roesner, D. H. Busch, N. W.
Alcock, Chem. Commun. 1998, 1437–1438; f) P. T. Glink, C. Schia-
vo, J. F. Stoddart, D. J. Williams, Chem. Commun. 1996, 1483–1490;
g) D. B. Amabilino, J. F. Stoddart, Chem. Mater. 1994, 6, 1159–1167;
h) J.-P. Sauvage, Acc. Chem. Res. 1990, 23, 319–327.
[3] a) G. Wenz, B.-H. Han, A. Müller, Chem. Rev. 2006, 106, 782–817;
b) F. Vçgtle, O. Lukin, Angew. Chem. 2005, 117, 1480–1501; Angew.
Chem. Int. Ed. 2005, 44, 1456–1477; c) B. B. Blight, K. A. Van
Noortwyk, J. A. Wisner, M. C. Jennings, Angew. Chem. 2005, 117,
1523–1528; Angew. Chem. Int. Ed. 2005, 44, 1499–1504; d) G. Bran-
cato, F. Coutrot, D. A. Leigh, A. Murphy, J. K. Y. Wong, F. Zerbetto,
Proc. Natl. Acad. Sci. USA 2002, 99, 4967–4971; e) D. G. Hamilton,
N. Feeder, J. K. M. Sanders, L. Prodi, W. Clegg, S. J. Teat, J. Am.
Chem. Soc. 1998, 120, 1096–1097; f) C. A. Hunter, J. Am. Chem.
Soc. 1992, 114, 5303–5311.
[4] a) E. R. Kay, D. A. Leigh, F. Zerbetto, Angew. Chem. 2007, 119, 72–
196; Angew. Chem. Int. Ed. 2007, 46, 72–191; b) V. Balzani, A.
Credi, S. Silvi, M. Venturi, Chem. Soc. Rev. 2006, 35, 1135–1149;
c) S. Bonnet, J.-P. Collin, M. Koizumi, P. Mobian, J.-P. Sauvage, Adv.
Mater. 2006, 18, 1239–1250; d) L. Raehm, J.-P. Sauvage in Molecular
Machines and Motors: Structure and Bonding (Ed.: J.-P. Sauvage),
Springer, Berlin, 2001, pp. 55–78; e) V. Balzani, A. Credi, F. M.
[8] a) S. E. Matthews, P. D. Beer, Supramol. Chem. 2005, 17, 411–435;
b) P. Lhotak, Top. Curr. Chem. 2005, 255, 65–95; c) Calixarenes
2001 (Eds.: Z. Asfari, V. Bçhmer, J. Harrowfield, J. Vicens), Kluwer,
Dordrecht, 2001; d) Calixarenes in Action (Eds.: L. Mandolini, R.
Ungaro), Imperial College Press, London, 2000; e) C. D. Gutsche,
Calixarenes Revisited, RSC, Cambridge, 1998; f) C. D. Gutsche, Cal-
ixarenes, RSC, Cambridge, 1989.
[9] a) A. Bogdan, Y. Rudzevich, M. O. Vysotsky, V. Bçhmer, Chem.
Commun. 2006, 2941–2952; b) L.-G. Lu, G.-K. Li, X.-X. Peng, C.-F.
Chen, Z.-T. Huang, Tetrahedron Lett. 2006, 47, 6021–6025; c) C.
Gaeta, M. O. Vysotsky, A. Bogdan, M. Bolte, V. Bçhmer, J. Am.
Chem. Soc. 2005, 127, 13136–13137; d) A. Arduini, F. Ciesa, M.
Fragassi, A. Pochini, A. Secchi, Angew. Chem. 2005, 117, 282–285;
Angew. Chem. Int. Ed. 2005, 44, 278–281; e) A. Bogdan, M. O. Vy-
sotsky, T. Ikai, Y. Okamoto, V. Bçhmer, Chem. Eur. J. 2004, 10,
3324–3330; f) L. Wang, M. O. Vysotsky, A. Bogdan, M. Bolte, V.
Bçhmer, Science 2004, 304, 1312–1314; g) I. Smukste, B. E. House,
D. B. Smithrud, J. Org. Chem. 2003, 68, 2559–2571; h) M. O. Vysot-
sky, M. Bolte, I. Thondorf, V. Bçhmer, Chem. Eur. J. 2003, 9, 3375–
3382; i) A. Arduini, F. Calzavacca, A. Pochini, A. Secchi, Chem.
Eur. J. 2003, 9, 793–799; j) Z.-T. Li, X.-L. Zhang, X.-D. Lian, Y.-H.
Yu, Y. Xia, C.-X. Zhao, Z. Chen, Z.-P. Lin, H. Chen, J. Org. Chem.
2000, 65, 5136–5142; k) A. Arduini, R. Ferdani, A. Pochini, A.
Secchi, F. Ugozzoli, Angew. Chem. 2000, 112, 3595–3598; Angew.
Chem. Int. Ed. 2000, 39, 3453–3456; l) Z.-T. Li, G.-Z. Ji, S.-D. Yuan,
Chem. Eur. J. 2007, 13, 3861 – 3870
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3869

P. D. Beer et al.
A.-L. Du, H. Ding, M. Wei, Tetrahedron Lett. 1998, 39, 6517–6520;
m) K. D. Shimizu, J. Rebek, Jr., Proc. Natl. Acad. Sci. USA 1995, 92,
12403–12407.
[13] The Windows version of EQNMR was used. For the original DOS
version, see:M. J. Hynes, J. Chem. Soc. Dalton Trans. 1993, 311–312.
[14] a) S. Blechert, S. J. Connon, Angew. Chem. 2003, 115, 1944–1968;
Angew. Chem. Int. Ed. 2003, 42, 1900–1923; b) S. Chang, R. H.
Grubbs, Tetrahedron 1998, 54, 4413–4450; c) R. H. Grubbs, S. J.
Miller, G. C. Fu, Acc. Chem. Res. 1995, 28, 446–452.
[15] H. D. Maynard, R. H. Grubbs, Macromolecules 1999, 32, 6917–6924.
[16] A. Andrievsky, F. Ahuis, J. L. Sessler, F. Vçgtle, D. Gudat, M.
Moini, J. Am. Chem. Soc. 1998, 120, 9712–9713.
[10] C. Fischer, M. Nieger, O. Mogck, V. Bçhmer, R. Ungaro, F. Vçgtle,
Eur. J. Org. Chem. 1998, 155–181.
[11] a) R. Wakabayashi, Y. Kubo, K. Kaneko, M. Takeuchi, S. Shinkai, J.
Am. Chem. Soc. 2006, 128, 8744–8745; b) J. Frey, T. Kraus, V. Heitz,
J.-P. Sauvage, Chem. Commun. 2005, 5310–5312; c) E. N. Guidry,
S. J. Cantrill, J. F. Stoddart, R. H. Grubbs, Org. Lett. 2005, 7, 2129–
2132; d) T. J. Kidd, D. A. Leigh, A. J. Wilson, J. Am. Chem. Soc.
1999, 121, 1599–1600.
[17] Unfortunately it was not possible to compare the binding properties
of 14d to those of 15d owing to a lack of the appropriate material.
[12] a) P. A. Gale, Acc. Chem. Res. 2006, 39, 465–475; b) M. J. Chmie-
lewski, J. Jurczak, Chem. Eur. J. 2005, 11, 6080–6094; c) K. Kaval-
lieratos, C. M. Bertao, R. H. Crabtree, J. Org. Chem. 1999, 64, 1675–
1683; d) K. Kavallieratos, S. R. de Gala, D. J. Austin, R. H. Crabtree,
J. Am. Chem. Soc. 1997, 119, 2325–2326.
Received: January 10, 2007
Published online: April 5, 2007
3870
www.chemeurj.org
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Chem. Eur. J. 2007, 13, 3861 – 3870