Anion induced displacement studies in naphthalene diimide containing interpenetrated and interlocked structures

Article abstract of DOI:10.1039/b819322c

This article describes investigations into the development of supramolecular systems capable of sensing anions through either displacement type assays or molecular motion. An electron deficient naphthalene diimide thread and an electron rich isophthalamid

Full text of DOI:10.1039/b819322c

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PAPER
www.rsc.org/njc | New Journal of Chemistry
Anion induced displacement studies in naphthalene diimide containing
interpenetrated and interlocked structureswz
Kathleen M. Mullen, Jason J. Davis and Paul D. Beer*
Received (in Durham, UK) 30th October 2008, Accepted 2nd December 2008
First published as an Advance Article on the web 16th January 2009
DOI: 10.1039/b819322c
This article describes investigations into the development of supramolecular systems capable of
sensing anions through either displacement type assays or molecular motion. An electron deficient
naphthalene diimide thread and an electron rich isophthalamide naphthohydroquinone
macrocycle were shown to form a coloured pseudorotaxane assembly. Investigations into the
ability of such interpenetrated systems to sense anions colorimetrically were undertaken. Anion
complexation at the isophthalamide group of the macrocycle causes displacement of the
naphthodiimide thread resulting in the loss of colour. The enhanced mechanically bonded binding
strength between the naphthodiimide axle and the naphthohydroquinone groups of the
macrocycle wheel in the corresponding rotaxane structure, however, was found to negate the
anion induced displacement process.
naphthodiimide threads. We have previously shown that
isophthalamide based macrocycles such as 1 strongly bind a
Introduction
variety of anions.9 Furthermore anion templation together
The field of anion supramolecular chemistry is rapidly growing
due to the realisation of the many important roles that anions
with p–p interactions between electron deficient positively
play in various environmental, chemical and biological
charged pyridinium guests and the electron rich hydroquinone
units of the macrocycle can result in high yields of interlocked
processes.1–3 Of particular importance is the development of
structures.5–8,29 Thus it was hypothesised that the macrocycle’s
systems capable of selectively sensing anions. Anion receptors
incorporating redox- or photo-active signalling components
have been used successfully in the development of selective
electron rich hydroquinone units may provide sufficient
p–p stacking to stabilise the threading of a neutral electron
deficient naphthalene diimide guest such as 2. Previous studies
anion sensors.4 This field has been extended recently to
incorporate the use of interlocked host structures such as
by Sanders et al. and Gunter et al. have shown that naphthalene-
diimide entities form stable complexes with crown
rotaxanes or catenanes to act as highly selective anion
complexing reagents.5–15
ether macrocycles through a series of p–p and C–Hꢀ ꢀ ꢀO
One powerful method of sensing anions that has been
interactions, which have been exploited to synthesise
used to advantage by the groups of Anslyn,16–18 Sessler,19
catenanes and rotaxanes.30–36 Therefore it is feasible that
Martınez-Ma
´ ´
nez,20,21 and Gale22 is the development of
naphthalene diimide guests may form stable interpenetrated
assemblies with the isophthalamide-type macrocycles via
analogous interactions. Subsequent addition of anions might
trigger the displacement and dethreading of the diimide moiety
as the anion coordinates to the isophthalamide macrocycle.
Furthermore such displacement is likely to result in an
observable colour change. The pseudorotaxane assembly is
predicted to be coloured due to charge transfer interactions
between the electron rich macrocycle and electron deficient
naphthalenediimide thread. Anion induced dissociation would
result in a colour change, thus the system has the potential to
operate as a displacement type assay capable of colorimetrically
sensing anions (see Scheme 1).
displacement assays, whereby anion binding results in the
expulsion of a dye and hence an associated colour change. Such
systems may be capable of acting as colorimetric sensors. In the
case of interpenetrated and interlocked molecules the dynamic
behaviour of such systems also enables molecular motion to be
utilised as a potential means of sensing anions. Although cations
have been frequently used to induce chemically driven molecular
motion, anion induced switching is to date underexploited. The
groups of Chiu,23,24 Leigh,25,26 Stoddart27 and Prodi28 have used
anions to induce the translocation of macrocycles in rotaxane
structures, and we have reported the first anion induced
circumrotation in catenane structures.11
With this in mind, this paper reports attempts towards the
synthesis of anion switchable rotaxanes incorporating neutral
Results and discussion
Chemistry Research Laboratory, University of Oxford, Mansfield
Road, Oxford, UK OX1 3TA. E-mail: paul.beer@chem.ox.ac.uk;
Fax: +44 (0)1865 272690; Tel: +44 (0)1865 285142
w Dedicated to Professor J. Rebek and Professor J. de Mendoza on the
occasion of their 65th birthdays.
z Electronic supplementary information (ESI) available: NMR and
UV pseudorotaxane binding studies of diimide 2 with macrocycles 1
and 8. ROESY spectra of rotaxane 11. See DOI: 10.1039/b819322c
Before anion displacement studies could be undertaken, it was
first necessary to determine whether naphthalene diimide
moieties would indeed thread through the cavity of isophthal-
amide based macrocycles such as 1. Thus the simple hexyl
substituted diimide thread 2 was synthesised according to
literature procedures.34
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Scheme 1 Proposed anion induced displacement assay of interlocked
structures incorporating naphthalene diimide threads.
1H NMR was used initially to investigate the binding
interactions between diimide 2 and hydroquinone macro-
cycle 1. Addition of 1 equivalent of diimide thread 2 to a
solution of macrocycle 1 in CDCl3 resulted in only minor
upfield shifts of the hydroquinone (Dd 0.09 ppm) and
diimide (Dd 0.03 ppm) protons indicating weak binding
(see ESIz Fig. S1).
This weak interaction could be attributed to insufficient p–p
stacking with the hydroquinone units. It is known that
naphthalene diimides display higher binding affinities for
dinaphtho-crown ethers rather than their hydroquinone
counter parts. It was hoped that modification of macrocycle
1 to incorporate two naphthohydroquinone units would be
sufficient to stabilise diimides in future pseudorotaxane and
rotaxane studies.
Scheme 2 Synthesis of macrocycle 8; (i) benzyl bromide, K2CO3,
DMF, 24 h, 23%; (ii) 2-bromoacetonitrile, K2CO3, acetone, D, 24 h,
99%; (iii) LiAlH4, diethyl ether, 3 h, 82%; (iv) 5-tert-butylisophthaloyl
dichloride, Et3N, dry DCM, 24 h, 92%; (v) Pd/C (10%), DMF,
EtOH, 24 h, 84%; (vi) bis-tosyltetraethylene glycol, Cs2CO3, DMF, D,
3 days, 15%.
The new macrocycle 8 was thus synthesised according
to Scheme 2. Reaction of 1,5-dihydroxynaphthalene with benzyl
bromide in the presence of K2CO3 afforded the mono-
protected naphthohydroquinone 3 in 23% yield. Reaction of
this mono-protected naphthalene 3 with bromoacetonitrile
followed by reduction with lithium aluminium hydride at
room temperature gave the primary amine, 5 in good
yields. Condensation of two equivalents of amine 5 with
5-tert-butylisophthaloyl dichloride in the presence of Et3N
afforded the benzyl protected precursor 6. Deprotection was
achieved using 10% Pd/C catalyst to give the macrocycle
precursor diol 7. The caesium cation mediated cyclisation
reaction of 7 with tetraethylene glycol-bis-para-tosylate under
high dilution conditions gave macrocycle 8 in 15% yield
(which is comparable to the yields obtained in the synthesis
of the analogous hydroquinone macrocycle 1).
1
Preliminary H NMR binding studies were undertaken to
determine the strength of binding between this naphtho-
hydroquinone macrocycle 8 and the naphthalene diimide
thread 2. Addition of 1 equivalent of diimide thread 2 to a
solution of macrocycle in CDCl3 resulted in significant upfield
shifts in the diimide proton a from 8.76 to 8.62 ppm which is
indicative of a shielding effect from the macrocycle (see Fig. 1).
The extent of this shift is comparable to other systems in
which a naphthohydroquinone crown is bound around a
diimide thread unit.30,36–38 Similarly the naphthohydroquinone
protons of the macrocycle have also been shifted upfield
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Fig. 1 1H NMR variable temperature binding study between macro-
cycle 8 and diimide 2 in CDCl3.
(with upfield shifts ranging between Dd 0.45 ppm for proton d
and 0.14 ppm for proton c). Conversely, downfield shifts for
the NH and CHint and CHext protons for the macrocycle were
observed (Dd ꢂ0.31, ꢂ0.4, and ꢂ0.15 ppm, respectively) as the
isophthalamide aromatic ring is in the deshielding region of
the diimide aromatics. Variable temperature studies were
also performed, and as expected, the extent of upfield shifts
for the diimide and naphthohydroquinone protons increased
upon decreasing temperature, confirming that pseudorotaxane
formation is in fast exchange and that complexation is
favoured at lower temperatures.
Further evidence of strong complexation between macrocycle
8 and diimide 2 arose from a UV-visible spectrum of the
pseudorotaxane. Addition of one equivalent of macrocycle 8
to a solution of diimide 2 in CHCl3 results in the appearance of
a dark pink colour arising from a charge transfer interaction
between the macrocycle and the diimide. A UV-visible
titration of a solution of 2 into a solution of 8 in CDCl3 was
performed. Analysis of the data by SPECFIT39 determined the
binding constant to be 355 Mꢂ1 with a calculated extinction
coefficient of 430 Mꢂ1 cmꢂ1 (see ESIz Fig. S2). This is in
a similar range to that observed in related crown-diimide
supramolecular systems.30,36–38
Fig. 2 Top: UV spectrum of the titration of sulfate into an equimolar
solution of diimide 2 and macrocycle 8 in CHCl3 (1.33 ꢃ 10ꢂ3 mol Lꢂ1);
bottom: relative changes in absorbance at 510 nm upon the addition of
10 equiv. of anion to an equimolar solution of diimide 2 and macro-
cycle 8 in CHCl3 (1.33 ꢃ 10ꢂ3 mol Lꢂ1).
TBA chloride were also undertaken in CHCl3. In each case
the colour of the solution decreased upon addition of anions
and a comparison of the relative changes in absorbance upon
the addition of 10 equivalents of various anions is shown in
Fig. 2. The largest change in absorbance was observed upon
the addition of TBA2(SO4) indicating that the dethreading
process was more effective with the dianion as compared to
anions such as chloride or dihydrogen phosphate. Nevertheless
it is clear that in a pseudorotaxane system anions are effective
in displacing the diimide guest.
Having established that the diimide thread 2 does form
stable pseudorotaxanes with macrocycle 8, investigations into
the use of anions to induce dissociation were undertaken. It
was anticipated that upon anion addition, the macrocycle
would preferentially coordinate to the anion leading to
displacement of the diimide thread component. Thus the
intensity of the charged transfer interaction resulting from
the diimide-macrocycle pseudorotaxane assembly would be
expected to decrease and anion induced ‘dethreading’ could be
monitored by UV-visible spectroscopy.
This anion induced dethreading behaviour was also
monitored by 1H NMR. To an equimolar mixture of macrocycle
8 and diimide 2 in CDCl3 an excess of TBA sulfate was added.
This resulted in the downfield shift in the diimide proton a to
8.76 ppm which is identical to the chemical shift of the diimide
thread in the absence of any macrocycle. Furthermore the
CHint and CHext protons shifted downfield due to anion
coordination, and these chemical shifts are the same as
that observed in a solution of macrocycle containing the
same number of equivalents TBA sulfate (see Fig. 3). Such
observations confirm that the addition of anions is indeed
resulting in the dethreading of this intermolecular system.
The addition of TBA sulfate to an equimolar solution of
diimide 2 and macrocycle 8 in CHCl3 resulted in a visible
colour change of the solution from dark pink to colourless.
The decrease in absorbance of the charged transfer band at
510 nm is indicative of the diimide being expelled from the
cavity of the macrocycle (see Fig. 2). Systems that result in
colour changes detectable by the naked eye in the presence
of anions are rare.18,19,22 Analogous titrations using TBA
fluoride, TBA dihydrogen phosphate, TBA benzoate and
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Fig. 3 (a) 1H NMR spectrum of an equimolar solution of macrocycle
8 and diimide 2; (b) 1H NMR spectrum of an equimolar solution of
macrocycle 8 and diimide 2 plus 10 equiv. of TBA sulfate; (c) 1H NMR
spectrum of macrocycle 8 and 10 equiv. of TBA sulfate. All spectra are
in CDCl3.
Scheme 4 Synthesis of naphthalenediimide rotaxane 11.
(particularly diimide proton a at 8.65 ppm, and urethane
proton at 6.73 ppm) were noted for comparison with such
entities in the planned rotaxanes.
Having established that anion triggered ‘dethreading’ was
possible in
a pseudorotaxane system incorporating the
Having successfully isolated the dumbbell 10, the reaction
was again repeated in the presence of 1 equivalent of
macrocycle 8 in order to synthesise the new rotaxane 11
(see Scheme 4). After three days at room temperature the
reaction was complete producing both dumbbell 10 (42%)
and the diimide rotaxane 11 (4%). The ES-MS analysis of the
diimide rotaxane 11 gave the expected mass peak at
m/z 2186.9528 [M + Na]+.
1H, COSY and ROESY NMR studies were used to
characterise the diimide rotaxane 11 (see Fig. 4). The position
of the diimide resonance a in the diimide rotaxane was
significantly upfield relative to its position in the uncomplexed
dumbbell component, shifting from 8.65 to 8.03 ppm. This is
attributed to substantial shielding from the naphthohydro-
quinone moieties in the macrocycle. Similarly the naphtho-
hydroquinone protons of the macrocycle have also been
shifted upfield (with upfield shifts of Dd 0.96 ppm for proton
d, 0.98 for proton a, 0.52 for proton e, 0.74 for proton b, 0.51
for proton f, and 0.56 ppm for proton c), which again is due to
shielding by the diimide moiety, and is indicative of a co-facial
naphthohydroquinone macrocycle 8 and diimide thread 2, it
was of interest to see whether molecular motion would be
possible in a permanently interlocked rotaxane system. Thus a
modified diimide thread 9 with hydroxy functionalised tethers
was synthesised. It was envisioned that a urethane stoppering
reaction with isocyanate stopper groups in the presence of
macrocycle could be used to synthesise a rotaxane. This
stoppering method has been used to advantage in the synthesis
of interlocked structures due to the mild reaction conditions it
employs.23,40,41 Thus control experiments were performed on
the synthesis of dumbbell 10 by reacting diimide thread 9
with the isocyanate stopper 13 in the presence of a tin catalyst
(see Scheme 3).
Dumbbell 10 was synthesised in reasonable yields (50%)
1
and characteristic H NMR chemical shifts of the dumbbell
Fig. 4 1H NMR spectrum of macrocycle 8 (top), compared to the
diimide rotaxane 11 (middle) and the dumbbell 10 (bottom) in CDCl3.
Scheme 3 Synthesis of diimide 9 and dumbbell 10.
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arrangement between the macrocycle and thread. Conversely,
the NH, CHint and the CHext protons are all shifted downfield
(Dd ꢂ0.84, ꢂ0.92 and ꢂ0.35 ppm, respectively) due to
the orientation of the isophthalamide aromatic ring in the
deshielding region of the diimide aromatics.
Further evidence for the interlocked nature of this system
was provided by ROESY experiments. Clear through space
interactions between the diimide proton peak a and the
macrocycle naphthohydroquinone protons a–f were observed
(see ESIz Fig. S3). Furthermore interactions between the
diimide proton and the ethoxy and NH amide protons of
the macrocycle were also evident which is indicative of an
interlocked structure in which the diimide is threaded through
the cavity of the macrocycle.
Fig. 5 UV titration of (TBA)2SO4 into a solution of diimide rotaxane
11 in CHCl3 (1.43 ꢃ 10ꢂ4 mol Lꢂ1).
Having isolated the diimide rotaxane 11, as in the case
for the pseudorotaxane counterparts, it was hypothesised
that the addition of anions to this system may result in the
displacement of the diimide as the macrocycle bound the anion
in its cavity (see Scheme 5). Furthermore the inclusion of the
urethane linkers may give the macrocycle an ideal second
station to bind in the presence of anions.
UV titration experiments with the diimide rotaxane 11 were
undertaken to determine if the addition of anions would
indeed disrupt the p–p interaction between the macrocycle
and diimide moiety. A solution of (TBA)2SO4 was titrated into
a solution of diimide rotaxane in CHCl3. Unfortunately little
change in the charge transfer absorbance band was observed
which could be attributed to changes in concentration due to
dilution rather than anion binding (see Fig. 5). Similar
titrations were performed using TBACl and TBAF, however
again only minor changes in the charge transfer absorbance
band were observed. The titration was again repeated but in
this case in the more competitive solvents acetonitrile and
DMSO. It should be noted that in acetonitrile and DMSO
pseudorotaxane formation between macrocycle 8 and diimide
Fig. 6 1H NMR spectrum in d6-DMSO of (top) diimide rotaxane 11
and (bottom) diimide rotaxane 11 plus 1 equiv. of (TBA)2SO4.
2 does not occur as p–p is not favoured in more polar solvents.
Again however, minimal changes in the UV absorbance of the
charge transfer band were observed indicating that the diimide
remained inside the cavity of the macrocycle.
An NMR titration in d6-DMSO was performed to determine
whether the diimide binding was weakened to any extent in
the presence of sulfate (see Fig. 6). Of particular importance
was the fact that the pink coloration arising from the
charge transfer interaction was present throughout the entire
titration. This indicates that again the diimide remained bound
inside the cavity of the macrocycle.
Closer inspection of the proton resonances for both the
diimide proton and the naphthohydroquinone macrocycle
protons confirmed this assumption by the fact that no changes
in their chemical shift were observed upon addition of sulfate.
Despite this, downfield shifts in both the NH and CHint
protons of the macrocycle were observed (Dd ꢂ1.83 and
ꢂ0.51 ppm, respectively). WinEQNMR39 analysis of the
titration data enabled an association constant of 75 Mꢂ1 to
be determined for a 1 : 1 binding equilibrium. It is thought that
the macrocycle in rotaxane 11 is capable of binding both the
anion and diimide moiety simultaneously and the dianion is
probably perched above the macrocycle.
Conclusion
This article describes efforts towards the development of
supramolecular assemblies capable of sensing anions either
Scheme 5 Anion induced shuttling anticipated in the naphthalene
diimide rotaxane 11.
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via use of pseudorotaxanes as displacement assays or through
the anion induced molecular motion in the case of rotaxanes.
We have shown that electron deficient naphthalene diimide
threads form stable pseudorotaxane assemblies with an
isophthalamide macrocycle incorporating naphthohydroquinone
arms. Furthermore, anion complexation at the isophthalamide
motif of the macrocycle causes dissociation of the diimide
thread from the cavity of the macrocycle, which in turn results
in an associated colour change. Thus this system has the
potential to act as a colorimetric anion sensor via an analyte
triggered dethreading mechanism.
2-(5-(Benzyloxy)naphthalene-1-yloxy)acetonitrile (4)
A solution of 1-benzyloxy-1-hydroxynaphthalene 3 (5.32 g,
21.3 mmol), bromoacetonitrile (2.80 g, 23.3 mmol) and K2CO3
(3.26 g, 23.3 mmol) in dry acetone (200 mL) was refluxed
under N2 for 24 hours. After this time the reaction mixture was
cooled to room temperature and filtered. The solvent was then
evaporated to give a brown oil which was redissolved in DCM
and filtered through a plug of silica. The solvent was then
removed in vacuo to give the pure product as a pale yellow
solid (6.07 g, 99%); mp 96–98 1C; m/z (ESI-MS) [M + H]+
290.1233 C19H16NO2 (calc. 290.1181); 1H NMR (300 MHz,
CDCl3) d 8.07 (1H, d, 3J 8.5 Hz, Ar–H), 7.78 (1H, d, 3J 8.5 Hz,
Ar–H), 7.51–7.54 (2H, m Ar–H), 7.33–7.45 (5H, m, Ar–H),
6.96 (2H, d, 3J 7.5 Hz, Ar–H), 5.25 (2H, s, CNCH2), 4.96
(2H, s, OCH2Ph); 13C NMR (75 MHz, CDCl3) d 154.4, 152.2,
137.3, 137.0, 128.7, 128.0, 127.5, 126.2, 125.3, 124.8, 117.2,
114.8, 114.0, 106.6, 106.1, 70.2, 53.8.
In an attempt to extend this principle to permanently
interlocked structures a new rotaxane 11 was successfully
synthesised. In spite of control experiments demonstrating that
the relatively weak p–p stacking interactions between a diimide
derivative and the naphthohydroquinone macrocycle could be
disrupted by anion binding, in the rotaxane the enhanced
effective mechanically bonded binding strength between such
components negates the anion induced displacement process.
Similar enhancement of the effective binding strength in inter-
locked systems, as compared to pseudorotaxane analogues,
has been recently reported for metal–ligand interactions.42
Leigh et al. have also shown that although strong non-covalent
interactions may be necessary to maximise the yield of
rotaxanes and catenanes, the strength of such interactions
provides significant energetic barriers that must be overcome
in order to achieve molecular motion.43,44 Thus in the future
design of systems capable of molecular motion, either these
templating interactions need to be significantly weakened in
the final product (through the removal of a template,
pH-dependent control, or photo- or electro-chemical induced
changes), and/or the preference for complexation to a second
station needs to be increased dramatically.
2-(5-(Benzyloxy)naphthalene-1-yloxy)ethylamine (5)
2-(5-(Benzyloxy)naphthalene-1-yloxy)acetonitrile 4 (6.07 g,
21.0 mmol) was dissolved in dry diethyl ether (200 mL) and
added dropwise to a suspension of LiAlH4 (1.75 g, 46 mmol) in
dry diethyl ether (400 mL) and the mixture was then stirred at
room temperature under N2 for 3 hours. Aqueous 10% NaOH
was added slowly until no further effervescence was observed.
NaCl(aq) (200 mL) was then added and the organic layer
separated. Diethyl ether (100 mL) was added to the aqueous
layer and stirred for 20 minutes. The organic layer was then
decanted. This procedure was repeated once more. The
organic layers were combined, dried over MgSO4 and
the solvent removed to give the product as a white solid
(5.02 g, 82%); mp 76–78 1C; m/z (ESI-MS) [M + H]+
294.1489 C19H20NO2 (calc. 294.1489); 1H NMR (300 MHz,
CDCl3) d 7.95 (1H, d, 3J 8.5 Hz, Ar–H), 7.89 (1H, d, 3J 8.5 Hz,
Ar–H), 7.52–55 (2H, m Ar–H), 7.34–7.44 (5H, m, Ar–H), 6.94
(1H, d, 3J 7.5 Hz, Ar–H), 6.88 (1H, d, 31J 7.5 Hz, Ar–H), 5.25
(2H, s, OCH2Ph), 4.17 (2H, m, CH2) 3.23 (2H, m, CH2);
13C NMR (75 MHz, CDCl3) d 154.4, 137.2, 128.6, 127.9,
127.3, 126.8, 126.7, 125.2, 125.1, 114.6, 114.3, 106.0, 105.6,
70.5, 70.1, 41.7.
Experimental
General considerations
Dry solvents were obtained by purging with nitrogen and then
passing through an MBraun MPSP-800 column. H2O was
de-ionised and microfiltered using a Milli-Qs Millipore
machine. Tetrabutylammonium sulfate was purchased from
Sigma-Aldrich as a 50% aqueous solution, which was
N,N-Bis(2-(5-(benzyloxy)naphthalen-1-yloxy)ethyl)-5-tert-
butylisophthalamide (6)
concentrated on
a rotary evaporator and subsequently
dehydrated by azeotroping with tetrahydrofuran and then
dried over phosphorus pentoxide in a vacuum desiccator. All
tetrabutylammonium salts were stored in a vacuum desiccator
over phosphorus pentoxide prior to use. All other solvents
and commercial grade reagents were used without further
purification.
2-(5-(Benzyloxy)naphthalene-1-yloxy)ethylamine 5 (5.02 g,
17.4 mmol) and Et3N (5 mL, excess) were dissolved in dry
DCM (100 mL) and the mixture was cooled in an ice bath to
0 1C. 5-tert-Butylisophthaloyl dichloride (2.14 g, 8.3 mmol)
was dissolved in dry DCM (50 mL) and added dropwise to the
reaction mixture. The reaction was stirred at 0 1C for 1 hour,
and then at room temperature for a further 2 hours, during
which time a precipitate was observed to have formed. This
precipitate was filtered to yield the product as a white solid
(5.9 g, 92%); mp 134–136 1C; m/z (ESI-MS) [M + Na]+
795.3408 C50H48N2O6Na (calc. 795.3405); 1H NMR
(300 MHz, CDCl3) d 7.94–7.97 (4H, m, Ar–H), 7.89 (1H, m,
Ar–H), 7.85 (1H, s, Ar–H), 7.82 (1H, s, Ar–H), 7.50–7.53 (4H,
m Ar–H), 7.31–7.43 (10H, m, Ar–H), 6.86–6.90 (4H, m,
Ar–H), 6.68 (2H, t, 2J 6 Hz, NH), 5.22 (4H, s, OCH2Ph),
Mass spectra were obtained using a Micromass GCT (EI)
instrument or
a Micromass LCT (ESMS) instrument.
Microwave reactions were carried out using a Biotage
Initiator 2.0 microwave. Melting points were recorded on a
Gallenkamp capillary melting point apparatus and are
uncorrected. Isophthalamide macrocycle 1,9 2,7-dihexyl-
benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone 234 and
1-benzyloxy-1-hydroxynaphthalene 345 were prepared as
described previously.
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4.33 (4H, m, CH2), 3.99 (4H, m, CH2), 1.32 (9H, s, tert-butyl);
13C NMR (75 MHz, CDCl3) d 167.0, 154.4, 154.0, 151.5,
137.5, 134.9, 128.9, 128.3, 127.9, 127.1, 126.5, 126.0, 125.7,
124.2, 114.7, 114.3, 110.0, 106.8, 106.4, 69.9, 67.0, 35.2, 31.4.
the product as fine pink crystals (0.33 g, 55%); mp 199–200 1C;
m/z (ESI-MS) [M]+ 489.1995 C26H30N2O6Na (calc. 489.1996);
1H NMR (300 MHz, CDCl3) d 8.70 (4H, s, NDI), 4.11–4.16
(4H, m, N–CH2), 3.56–3.61 (4H, m, O–CH2), 1.67–1.73
(4H, m, CH2), 1.49–1.55 (4H, m, CH2), 1.37–1.42 (8H, m,
CH2), 1.25 (2H, s, OH); 13C NMR (75 MHz, DMSO) d 162.9,
130.8, 126.5, 61.0, 32.8, 27.9, 26.9, 25.7.
5-tert-Butyl-N,N-bis(2-(5-hydroxynaphthalen-1-yloxy)ethyl)-
isophthalamide (7)
N,N-bis(2-(5-(benzyloxy)naphthalen-1-yloxy)ethyl)-5-tert-butyl-
isophthalamide 6 (5.9 g, 7.6 mmol) and 10% Pd on carbon
(0.60 g, 10% by weight) were suspended in 4 : 1 DMF–EtOH
(200 mL). The mixture was thoroughly degassed and then
purged with H2 and then stirred vigorously under H2
overnight. After this time the reaction mixture was filtered
through celite and the solvent removed in vacuo. The crude
material was recrystallised from MeOH–DCM–hexane to give
the pure product as a white solid (3.4 g, 84%); mp 138–141 1C;
m/z (ESI-MS) [M + Na]+ 615.2458 C36H36N2O6Na (calc.
615.2466); 1H NMR (300 MHz, CDCl3) d 8.98 (2H, s, Ar–H),
8.36 (2H, t, 2J 5 Hz, NH), 8.27 (1H, s, Ar–H), 8.11
(2H, s, Ar–H), 7.82 (4H, d, 3J 8 Hz, Ar–H), 7.34 (2H, t,
3J 8 Hz, Ar–H), 7.23 (2H, t, 3J 8 Hz, Ar–H), 6.98 (2H, d,
6,60-(1,3,6,8-Tetraoxobenzo[lmn][3,8]phenanthroline-
2,7(1H,3H,6H,8H)-diyl) bis(hexane-6,1-diyl) bis(4-(bis(4-tert-
butylphenyl)(phenyl)methyl) phenyl carbamate) (10)
The amine stopper 128 (85 mg, 0.19 mmol) and triphosgene
(28 mg, 0.094 mmol) were dissolved in dry, degassed toluene
(50 mL). Et3N (20 mg, 0.20 mmol) was then added and the
mixture was heated to 70 1C for 4 hours. After this time the
reaction mixture was filtered and the solvent removed in vacuo
to give the isocyanate intermediate 13 in quantitative yield.
This was then dissolved in CHCl3 (10 mL) and added to a
solution of diimide 9 (40 mg, 0.086 mmol) and dibutyl tin
dilaurate (16 mg, 0.025 mmol) in CHCl3 (10 mL). The reaction
mixture was then stirred at room temperature, under N2 for
5 days. After this time the solvent was evaporated and the
residue purified by preparative TLC (eluent: CD2Cl2–3%
MeOH) to give the product as a white solid (61 mg, 50%);
3
3J 8 Hz, Ar–H), 6.93 (2H, d, J 8 Hz, Ar–H), 4.36 (4H, m,
CH2), 3.97 (4H, m, CH2), 1.32 (9H, s, tert-butyl); 13C NMR
(75 MHz, CDCl3) d 205.5, 167.1, 154.3, 152.9, 151.6, 134.9,
127.0, 125.3, 124.6, 123.5, 114.5, 113.2, 108.7, 108.6, 105.2,
66.6, 39.5, 34.7, 30.6.
mp 164–166 1C; m/z (ESI-MS) [M
+
H]+ 1413.77
C94H100N4O8 (calc. 1413.76); 1H NMR (300 MHz, CDCl3)
d 8.65 (4H, s, NDI), 7.00–7.21 (36H, m, Ar–H), 6.73 (2H, s,
NH), 4.04–4.13 (8H, m, CH2), 1.55–1.69 (8H, m, CH2), 1.40
(8H, m, CH 2), 1.21 (36H, s, CH3); 13C NMR (75 MHz,
CDCl3) d 162.8, 153.8, 148.4, 147.2, 143.7, 142.2, 135.7, 131.8,
131.1, 131.0, 130.7, 127.3, 126.7, 126.6, 125.7, 124.2, 117.4,
65.2, 40.9, 34.3, 31.4, 28.5, 27.7, 26.5, 25.7.
Naphthohydroquinone macrocycle (8)
A
solution containing the macrocycle precursor (1.37,
2.6 mmol) and bis-tosyltetraethylene glycol (1.27 g, 2.6 mmol)
in dry degassed DMF (500 mL) was added dropwise over
6 hours to a solution of Cs2CO3 in dry degassed DMF (200 mL)
at 80 1C. The reaction mixture was then heated at 80 1C under
nitrogen for a further 3 days. After this time the solvent was
removed in vacuo and the crude material was purified via
column chromatography using a 30% EtOAc–hexane to
EtOAc eluent gradient. The pure product was recrystallised
from toluene to yield a white solid (290 mg, 15%); mp
130–132 1C; m/z (ESI-MS) [M + Na]+ 773.3410 C44H50N2O9Na
(calc. 773.3409); 1H NMR (300 MHz, CDCl3) d 7.96
(2H, s, Ar–H), 7.79 (2H, d, 3J 8.5 Hz, Ar–H), 7.63–7.67
Diimide rotaxane (11)
The amine stopper 128 (293 mg, 0.65 mmol) and triphosgene
(91 mg, 0.31 mmol) were dissolved in dry, degassed toluene
(100 mL). Et3N (52 mg, 0.51 mmol) was then added and the
mixture was heated to 70 1C for 4 hours. After this time the
reaction mixture was filtered and the solvent removed in vacuo
to give the isocyanate intermediate in quantitative yield. This
was then dissolved in CHCl3 (10 mL) and added to a solution
of diimide 9 (100 mg, 0.21 mmol), macrocycle 8 (160 mg,
0.21 mmol) and dibutyl tin dilaurate (40 mg, 0.063 mmol) in
CHCl3 (20 mL). The reaction mixture was then stirred at room
temperature, under N2 for 5 days. After this time the solvent
was evaporated and the residue purified by preparative TLC
(eluent: CD2Cl2–3% MeOH) to give the product both dumb-
bell 10 (128 mg, 42%) and the diimide rotaxane as a pink solid
(18 mg, 4%); mp 172–174 1C; m/z (ESI-MS) [M + Na]+
2186.9528 C138H150N6O17Na (calc. 2187.0983); 1H NMR
(300 MHz, CDCl3) d 8.59 (1H, s, CHint), 8.33 (2H, s, CHext),
8.03 (4H, s, a-NDI), 7.43 (2H, s, NHamide), 7.30 (4H, d, 3J
8.5 Hz, Ar–H), 7.00–7.19 (36H, m, Ar–H), 6.82 (2H, d,
3
3
(3H, m, Ar–H), 7.21 (2H, t, J 8 Hz, Ar–H), 7.05 (4H, t, J
8 Hz, Ar–H), 6.68 (2H, 3d, J 8 Hz, Ar–H), 6.59 (2H, t, 2J 5 Hz,
3
NH), 6.43 (2H, d, J 8 Hz, Ar–H), 4.16 (4H, m, OCH2), 3.98
(4H, m, OCH2), 3.90 (4H, m, OCH2), 3.84 (4H, m, OCH2),
3.65 (8H, m, OCH2), 1.28 (9H, s, tert-butyl); 13C NMR
(125 MHz, CDCl3) d 166.7, 154.1, 153.6, 151.0, 134.7, 126.5,
126.0, 125.7, 125.2, 123.6, 114.1, 113.7, 105.9, 105.4, 19.0, 70.1,
69.9, 68.9, 67.6, 67.1, 54.9, 34.7, 31.0.
2,7-Bis(6-hydroxyhexyl)benzo[lmn][3,8]phenanthroline-
1,3,6,8(2H,7H)-tetraone (9)
1,4,5,8-Naphthalenetetracarboxylic dianhydride (0.35 g,
1.3 mmol), 6-aminohexanol (0.34 g, 2.87 mmol) and dry
Et3N (0.2 mL) were suspended in dry, degassed DMF (15 mL)
and then subjected to microwave irradiation at 140 1C for
10 minutes. Upon cooling the product precipitated from
solution, was filtered and washed with cold DMF to yield
3
3J 8.0 Hz, d), 6.69 (4H, m, a e), 6.31 (2H, t, J 7.0 Hz, b), 6.16
(2H, d, 3J 8.0 Hz, f), 5.86 (2H, d, 3J 7.0 Hz, c), 4.08–4.12 (4H, m,
CH2), 3.79–3.95 (28H, m, OCH2), 1.56–1.74 (12H, m, CH2),
1.37 (13H, m, CH2, CH3macro), 1.21 (36H, s, CH3dumbbell);
13C NMR (75 MHz, CDCl3) d 160.0, 153.9, 153.3, 153.0, 152.8,
ꢁc
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New J. Chem., 2009, 33, 769–776 | 775

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148.4, 147.2, 143.8, 142.0, 136.0, 133.5, 131.8, 131.1, 130.7,
129.5, 127.3, 125.7, 125.1, 125.0, 124.8, 124.2, 123.3, 121.4,
117.4, 114.1, 113.1, 105.6, 104.4, 71.1, 70.7, 69.5, 67.6, 67.0,
64.9, 63.7, 41.0, 40.9, 35.3, 34.3, 31.4, 31.2, 28.5, 28.0,
26.6, 25.9.
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Acknowledgements
We thank the EPSRC for a postdoctoral fellowship (KMM).
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776 | New J. Chem., 2009, 33, 769–776