A ferrocene functionalized rotaxane host system capable of the electrochemical recognition of chloride

Article abstract of DOI:10.1039/c0ob00458h

A ferrocene appended rotaxane is prepared by chloride anion templation and ring closing metathesis. Upon removal of the chloride template, the rotaxane is demonstrated to be selective for chloride over more basic oxoanions by ¹H NMR spectroscop

Full text of DOI:10.1039/c0ob00458h

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PAPER
A ferrocene functionalized rotaxane host system capable of the
electrochemical recognition of chloride†
Nicholas H. Evans and Paul D. Beer*
Received 20th July 2010, Accepted 6th October 2010
DOI: 10.1039/c0ob00458h
A ferrocene appended rotaxane is prepared by chloride anion templation and ring closing metathesis.
Upon removal of the chloride template, the rotaxane is demonstrated to be selective for chloride over
more basic oxoanions by 1H NMR spectroscopy and electrochemistry, in marked contrast to an acyclic
analogue - the first example of a solution based redox-active interlocked host system capable of the
electrochemical recognition of anions.
Introduction
Rotaxanes, interlocked molecules comprising of a macrocyclic
component locked onto an axle by bulky stopper groups, have
been at the forefront of research into molecular machine-like
nanotechnological applications due to the possibilities of shut-
tling and/or pirouetting of their components.1 However, these
molecules also possess unique topologically constrained cavities
which may be exploited to selectively bind guest species for future
chemical sensory purposes.2 Despite this intriguing possibility,
only a few examples of designed rotaxane host systems that bind
charged species in their cavities have been reported to date.3,4
Due to the challenges of recognising anions (such as their low
charge densities, various geometries, high hydration energies and
pH dependence),5 rotaxane cavities are promising candidates for
anion binding. Our group has previously synthesised a range
of solution and surface confined rotaxanes by rational use of
anion templation, and have demonstrated such interlocked host
Fig. 1 Schematic representation of the use of a ferrocene-appended
rotaxane to electrochemically sense anions.
systems to selectively bind anions in highly competitive solvent
mixtures.4a–i
To achieve selective sensing of guests in such rotaxane hosts,
appropriate reporter group functionality needs to be incor-
porated into the interlocked molecular framework to provide
a response (either optical or electrochemical). Relatively few
examples have been designed and constructed to exhibit such
sensory behaviour3a,c–d,4b,d,j and only one electrochemically senses
anions, when confined to a surface.4d With the aim to selectively
sensing chloride electrochemically in solution, our attention has
turned towards attaching the redox-active ferrocene group to a
rotaxane (see Fig. 1). Ferrocene has been demonstrated to be
suitable for the detection of anions in a wide range of acyclic and
macrocyclic receptors.6 However, its appearances in rotaxanes as
a stopper7 or as part of the macrocyclic component4d,8 are rare
compared to the numerous examples of non-interlocked ferrocene
anion receptors.
In this paper we report the synthesis of the first redox-active
rotaxane capable of electrochemically recognising anionic guest
species, with a notably different electrochemical response to
chloride compared to oxoanions being observed.
Results and discussion
Design, synthesis and characterization
Department of Chemistry, Inorganic Chemistry Laboratory, University of
Oxford, South Parks Road, Oxford, UK, OX1 3QR. E-mail: paul.beer@
chem.ox.ac.uk; Fax: +44 1865 272960; Tel: +44 1865 285182
† Electronic supplementary information (ESI) available: Spectral charac-
terisation of novel compounds; protocols for 1H NMR and electrochemical
titrations, plus titration data. See DOI: 10.1039/c0ob00458h
To achieve the electrochemical recognition of an anion by a rotax-
ane, installation of an appropriate reporter group to a rotaxane
capable of binding anions is required. Integration of a redox-active
ferrocene moiety into such a rotaxane anion host system could
be accomplished via a direct C–C bond to the isophthalamide
92 | Org. Biomol. Chem., 2011, 9, 92–100
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group of an anion binding rotaxane’s macrocyclic component as
illustrated in Fig. 2. The chloride salt of rotaxane 1+PF6- could be
prepared by a ring closing metathesis (RCM) reaction of an appro-
priately functionalized bis-vinyl appended macrocyclic precursor
and methyl pyridinium chloride axle, the two rotaxane precursor
components self-assembling in solution by a combination of anion
templation, p–p stacking and hydrogen bonding.4a,c Following an-
ion exchange rotaxane 1+PF6- contains a cavity that is anticipated
to be selective for chloride,4a,c,e,i while the presence of a proximal
ferrocene would enable reporting of an anion binding event by the
rotaxane via cathodic shifts in the Fc/Fc+ redox couple.9
achieved by following a literature procedure for the Suzuki
coupling of ferroceneboronic acid with iodo-arene compounds,10
but using microwave irradiation for 30 min rather than refluxing
for several days. Preparing iodo compound 2 and submitting it
to these reaction conditions, followed by workup and column
chromatography, allowed isolation of target compound 3 in a
respectable yield of 58%. Model 3 was subsequently characterized
by 1H and 13C NMR spectroscopy and high resolution mass
spectrometry.
Having successfully demonstrated that it was possible to couple
ferrocene to an isophthalamide motif, synthesis of target rotaxane
1+PF6- was carried out as shown in Schemes 2 and 3. Preparation
of macrocycle precursor 5 was originally attempted by preparing
compound 45c and exposing this to the same Suzuki conditions
as for compound 2 (Route A in Scheme 2). Disappointingly, a
repeatedly low yield (15–20%) for the formation of 5 was observed
after workup and silica gel chromotography. In the belief that the
presence of the terminal vinyl groups were interfering with the
Suzuki coupling, an alternative route to 5 was pursued (Route B
in Scheme 2). Pleasingly, the Suzuki coupling of compound 7 to
form 8, occurred in a significantly higher yield of 55%. Removal
of the benzyl protecting groups was achieved quantitatively by
hydrogenation to yield 9 which was alkylated to produce the
desired bis-vinyl appended precursor 5.
Rotaxane 1+Cl- was prepared by RCM reaction of equimolar
amounts of 5 and methyl pyridinium chloride axle 10+Cl-4a in
dichloromethane solution, in the presence of 10% (by wt) Grubbs’
2nd generation catalyst. The rotaxane was isolated in 25% yield
after careful separation from other components in the reaction
mixture by silica gel preparatory thin layer chromatography.
Subsequent removal of the chloride ion template via anion
exchange by washing with NH4PF6 furnished the desired rotaxane
-
Fig. 2 Target rotaxane 1+PF6
.
-
salt 1+PF6 (Scheme 3).
Initial synthetic investigations were therefore undertaken to find
appropriate conditions for the direct appendage of ferrocene to
an isophthalamide motif by attempting the synthesis of acyclic
model system 3 (Scheme 1). The attachment of ferrocene was
Both salts were characterized by 1H (1D and 2D) and 13C (and
in the case of 1+PF6- by 19F and 31P) NMR spectroscopy and high
resolution mass spectrometry.
1
Comparison of the H NMR spectra of the rotaxane 1+Cl-
with macrocycle precursor 5 and axle 10+Cl- provides evidence of
the interlocked nature of the rotaxane (Fig. 3). The success of the
RCM reaction is indicated by the loss of peak o and the sharpening
of multiplet n to a pseudo-singlet, these signals arising from the
vinylic protons of the macrocycle precursor, with o lost as ethene,
the by-product of the reaction. The spectra indicate three regions
of interactions between the macrocyclic and axle components of
the rotaxane. The first, the isophthalamide clefts, where strong
upfield shifts in the axle signals r and s and downfield shifts
in the macrocycle signals e and f , due to competitive hydrogen
bond interactions between these protons and the chloride anion
template, are observed. Second, the hydroquinone protons i and j
have split and moved upfield, indicative of p–p stacking with the
electron poor pyridinium unit. Finally, there is a large downfield
shift in N-methyl peak p, indicating hydrogen bonding to the
polyether oxygens of the macrocyclic component. Upon exchange
to the hexafluorophosphate salt, there are upfield shifts of the
isophthalamide cavity protons e, f , r and s, due to the removal of
the chloride anion template. However, the hydroquinone protons i
and j remain split and upfield compared to macrocycle precursor
5, indicating the p–p stacking between two components, and that
the rotaxane species remains interlocked.
Scheme 1 Synthesis of model 3.
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Scheme 2 Synthetic routes to macrocyclic precursor 5.
-a
Table 1 1 : 1 Association constants, K, of model 3 and rotaxane 1+PF6
The cationic fragment 1+ is to be found at m/z ~ 1801.86 in
high resolution electrospray mass spectra of both rotaxane salts.
Conclusive evidence of the interlocked nature of the rotaxane
chloride and hexafluorophophate salts was provided by the
observation of numerous through space interactions between
macrocycle and axle components in 2D ROESY 1H NMR spectra
(see Fig. 4).
-c
Anion
Model 3b
Rotaxane 1+PF6
Cl-
170
100
450
40
4200d
640
640
-
H2PO4
BzO-
-
HSO4
1560
a Anions added as TBA salts. T = 293 K. Errors < 10%. b Solvent: CD3CN,
peak monitored: amide. c Solvent: 1 : 1 CDCl3:CD3OD, peak monitored:
cleft pyridinium. d K > 104 M-1 in CD3CN.
Anion recognition studies
1H NMR Titrations. The anion binding properties of rotaxane
1+PF6 and, for comparison, acyclic ferrocene isophthalamide
-
derivative 3 were investigated by 1H NMR titration experiments.‡
NMR samples of the two compounds were prepared, to which
aliquots of tetrabutylammonium (TBA) salts of various anions
were added. The chemical shifts of peaks arising from protons
in the isophthalamide groups were monitored. In all cases the
anion binding event was observed to be fast on the NMR
timescale allowing for the calculation of association constants by
the computer program winEQNMR2,11 with data fitting to a 1 : 1
binding model (see Table 1).
With model 3, the anions are bound weakly in CD3CN and
generally in the order of their basicity, i.e. benzoate > dihydrogen
phosphate > hydrogen sulfate. Chloride is bound slightly more
strongly than dihydrogen phosphate and hydrogen sulfate anions
because of the size-fit complementarity with the isophthalamide
cleft by the spherical monoatomic halide anion.12
‡ While perhaps being more appropriate for comparison to rotaxane
-
1+PF6 than acyclic model 3, the macrocyclic component of the rotaxane
proved very difficult to isolate pure in sufficient quantities for anion
recognition studies. In addition, it was also found to have low solubility in
acetonitrile, the solvent used in the electrochemistry investigations.
1
An initial H NMR titration was undertaken with rotaxane
-
1+PF6 and TBACl in CD3CN. Exceptionally strong 1 : 1 binding
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Fig. 3 Partial 1H NMR spectra of a) macrocycle precursor 5, b) rotaxane
1+Cl- and c) axle 10+Cl- Solvent: CDCl3. See Scheme 3 for proton labels.
rotaxane 1+PF6- in comparison to model 3. Most notably chloride
- the least basic of the anions - is now bound the most strongly.
Evidence of the origin of this is provided in the appearance of the
titration curves (see Fig. 5). For chloride, the cleft proton of the
pyridinium isophthalamide (proton r in Scheme 3) moves down-
field upon addition of the anion, whereas for the oxoanions, this
proton moves upfield. This is indicative of an alternative binding
mode for these anions - presumably they are too large to penetrate
into the cavity of the rotaxane and associate peripherally instead.
Scheme 3 Synthesis of rotaxane 1+X- (X- = Cl-, PF6-).
was observed (K > 104 M-1). This is not unexpected: the rotaxane
is positively charged, while the model is neutral. To allow for
meaningful comparison of association constants of different an-
ions with the rotaxane, the highly competitive solvent system 1 : 1
CDCl3:CD3OD was therefore used in subsequent titrations. There
is a marked difference in selectivity of binding of the anion by
Electrochemical anion sensory studies. In order to evaluate
the electrochemical sensory properties of model 3 and rotaxane
-
1+PF6 , cyclic and square wave voltammograms were recorded in
0.1 M TBAPF6 CH3CN solution.
Model 3 exhibits a quasi-reversible oxidation for the Fc/Fc+
redox couple with E1/2 = +85 mV (compared to E1/2(ferrocene) = 0 V).
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-
Fig. 5 Plot of chemical shift of pyridinium cleft proton of rotaxane 1+PF6
versus equivalents of TBA salt added.
Table 2 Shift in Fc/Fc+ redox couple of model 3 upon addition of anionsa
Anion
DE1/2/mV
Cl-
-20
-80b
-10b
-10
-
H2PO4
BzO-
-
HSO4
a Anions added as TBA salts. Electrolyte: 0.1 M TBAPF6 in CH3CN. Ref-
erence electrode: Ag/AgCl. Working electrode: Glassy Carbon. Auxiliary
electrode: Platinum. 10 equivalents of anions added. Values reported to
nearest 5 mV. T = 293 K. b Shift of oxidation peak, DEpa, due to loss of
reversibility.
1
-
Fig. 4 Section of H ROESY NMR spectrum of rotaxane 1+PF6 with
through space intercomponent interactions highlighted. See Scheme 3 for
proton labels.
Fig. 6 CVs of model 3 in 0.1 M TBAPF6/CH3CN upon the addition of
aliquots of TBACl (Potential compared to Ag/AgCl reference).
Upon progressive addition of stoichiometric equivalents of anions
cathodic shifts of the waves were observed: the maximum observed
shifts in the redox wave being summarised in Table 2. These
cathodic shifts can be attributed to the binding of the anion
by the isophthalamide cleft protons, facilitating oxidation of
ferrocene to ferrocenium. As chloride is added, a stepwise shifting
of the quasi-reversible redox wave is observed, to a value of
-20 mV upon addition of 10 equivalents of TBACl (see Fig. 6). In
contrast, with dihydrogen phosphate and benzoate there is a loss of
reversibility upon the addition of only small amounts of anion (1–
2 equivalents). The disappearance of the reduction wave indicates
either that the complexed anion-ferrocenium cation interaction is
disfavouring reduction back to ferrocene or that an EC mechanism
is in operation. Upon the addition of hydrogen sulfate the redox
wave remains reversible throughout but only a modest cathodic
shift is observed.
-
Rotaxane 1+PF6 also displays a quasi-reversible Fc/Fc+ redox
couple, but with E1/2 = +115 mV (compared to E1/2(ferrocene) = 0 V).
The more anodic potential for the rotaxane compared to acyclic
model system 3 is expected as the rotaxane is positively charged
which disfavours oxidation of the ferrocene moiety. Like the
model, upon addition of chloride and hydrogen sulfate to samples
of rotaxane, the redox couple remains quasi-reversible, while the
addition of approximately 2 equivalents of dihydrogen phosphate
or benzoate causes a loss of reversibility in the redox wave (see
Fig. 7 for CVs of chloride and dihydrogen phosphate titrations).
Not only is the magnitude of cathodic shift for chloride larger than
any of the oxoanions at equimolar concentrations of rotaxane host
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-
Table 3 Shift in Fc/Fc+ redox couple of rotaxane 1+PF6 upon addition
ciation occurs on the periphery of the rotaxane structure, it is
hypothesised that a through-space communication mechanism is
in operation between the rotaxane’s ferrocene redox centre and the
oxoanion.13
of anionsa
DE1/2/mV
Anion
After 1 eq. of anion
After 10 eq. of anion
Cl-
-20
-10
-15
-15
-20
Conclusions
-
H2PO4
-100b
-25b
-40
BzO-
A redox-active ferrocene functionalized rotaxane host system has
been prepared by chloride anion templation. Upon exchange of
the chloride anion template for the non-coordinating hexafluo-
rophosphate anion 1H NMR anion titration investigations reveal
that chloride is bound selectively over more basic oxoanions by
the rotaxane: this is due to a complementary size match of the
interlocked cavity for the monoatomic chloride anion, whereas
oxoanions are too large to penetrate the cavity and associate
peripherally. It has also been demonstrated that the rotaxane
displays electrochemical recognition for chloride as evidenced by
a maximum cathodic shift response of the Fc/Fc+ redox couple
being observed at equimolar concentrations of rotaxane host
and halide anion guest, whereas excess equivalents are required
for oxoanions. The incorporation of redox-active groups into
interlocked host design is continuing in our laboratories.
-
HSO4
a Anions added as TBA salts. Electrolyte: 0.1 M TBAPF6 in CH3CN. Ref-
erence electrode: Ag/AgCl. Working electrode: Glassy Carbon. Auxiliary
electrode: Platinum. Values reported to nearest 5 mV. T = 293 K. b Shift of
oxidation peak, DEpa, due to loss of reversibility.
Experimental
General
Commercially available solvents and chemicals were used without
further purification unless stated. Where dry solvents were used,
they were degassed with nitrogen, dried by passing through a
MBraun MPSP-800 column and then used immediately. Deionised
water was used in all cases. Triethylamine was distilled from and
stored over potassium hydroxide. Thionyl chloride was distilled
from triphenyl phosphate. Grubbs’ 2nd generation catalyst was
stored in a desiccator. Microwave reactions were carried out using
a Biotage Initiator 2.0 microwave
NMR spectra were recorded on Varian Mercury 300, Varian
Unity Plus 500 and Bruker AVII 500 (with 13C Cryoprobe)
spectrometers. Electrospray mass spectra were carried out on
Micromass LCT and Bruker micrOTOF spectrometers. Melting
points were recorded on a Gallenkamp capillary melting point
apparatus and are uncorrected.
-
Fig. 7 Selected CVs of rotaxane 1+PF6 in 0.1 M TBAPF6/CH3CN
upon the addition of aliquots of (a) TBACl and (b) TBAH2PO4 (Potential
compared to Ag/AgCl reference).
Synthesis
5-Iodoisophthalic acid,14 iodo-arene precursor 4,4c amine 6,15
2-(allyloxy)ethyl 4-methylbenzenesulfonate16 and chloride axle
10+Cl-4a were prepared by literature procedure.
and anion guest, but the cathodic shift of 20 mV is observed at 1
equivalent of added chloride anion with negligible further shift
(< 5 mV) observed upon addition of further equivalents (see
Table 3). These observations support the theory that only chloride
is able to bind strongly within the interlocked cavity, with
its presence being communicated to ferrocene presumably via
a through-bond mechanism.13 With the oxoanions, there is a
continued cathodic shift in the redox wave upon the addition
of further equivalents of anion.§ Taking into account the 1H
NMR anion binding results, which suggest the oxoanion asso-
N1, N3-Dihexyl-5-iodoisophthalamide (2). To a solution of 5-
iodoisophthalic acid (2.00 g, 6.85 mmol) dissolved in dry CH2Cl2
(100 mL), oxalyl chloride (1.74 g, 1.16 mL, 13.7 mmol) and dry
DMF (a drop, catalytic amount) were added, after which the
solution was stirred under a nitrogen atmosphere until all solid
had gone into solution. The solution was then concentrated to
leave an orange oily film. This was redissolved in dry CH2Cl2
(100 mL), cooled to 0 ◦C, and NEt3 (5 mL, excess) and n-
hexylamine (1.39 g, 1.81 mL, 13.7 mmol) were added. This reaction
mixture was stirred for 16 h. The resulting organic solution was
washed with 1 M HCl(aq) solution (3 ¥ 100 mL), sat. NaHCO3(aq)
§ Attempts at electrochemical anion recognition competition experiments
(e.g. addition of chloride to rotaxane 1+PF6 in the presence of excess
-
equivalents of oxoanions) were undertaken but proved inconclusive due to
irreversible electrochemical behaviour.
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solution (2 ¥ 100 mL) and H2O (2 ¥ 100 mL). The organic fraction
was dried over MgSO4, the solvent removed in vacuo and then
purified by silica gel column chromatography (pentane–EtOAc
4 : 1 to 1 : 1) to yield iodo-arene 2 as a white solid (1.44 g, 46%).
Mp = 100 ◦C; dH(300 MHz, CDCl3) 8.15 (2H, s, isophthalamide
ArH4 & H6) 8.06 (1H, s, isophthalamide ArH2), 6.42 (2H, t, 3J =
5.3 Hz, NH), 3.40–3.46 (4H, m, NHCH2CH2), 1.56–1.66 (4H, app
quartet, NHCH2CH2), 1.29–1.42 (12H, m, 3 ¥ CH2), 0.88–0.92
(6H, m, CH3); dC(75.5 MHz, CDCl3) 165.5, 138.5, 136.7, 124.4,
94.3, 40.4, 31.5, 29.4, 26.7, 22.5, 14.0; m/z (ES) 459.1517 ([M +
H]+, C20H32IN2O2 requires 459.1509), 459 (98%, [M + H]+), 476
(12, [M + NH4]+), 481 (98, [M + Na]+), 491 (65, [M + CH3OH +
H]+), 497 (44, [M + K]+), 513 (100, [M + CH3OH + Na]+).
product isolated after silica gel column chromatography (CH2Cl2–
CH3OH 98 : 2) as an orange oil (151 mg, 48%).
dH(300 MHz, CDCl3) 7.99 (2H, d, 4J = 1.5 Hz, isophthalamide
ArH4 & H6), 7.90 (1H, t, 4J = 1.5 Hz, isophthalamide ArH2), 6.86
3
(8H, app s, hydroquinone ArH), 6.78 (2H, t, J = 5.9 Hz, NH),
5.88–6.01 (2H, m, CH CH2), 5.19–5.35 (4H, m, CH CH2), 4.72
(2H, app s, Fc CpH), 4.39 (2H, app s, Fc CpH), 4.07–4.15 (12H, m,
3 ¥ CH2), 4.04 (5H, s, Fc Cp’H), 3.88 (4H, app quartet, NHCH2),
3.78 (4H, m, CH2); dC(75 MHz, CDCl3) 167.1, 153.2, 152.6, 141.3,
134.7, 134.5, 127.4, 122.1, 117.4, 115.6, 115.3, 82.9, 72.3, 69.7,
68.5, 68.0, 67.1, 66.7, 66.6, 39.8; m/z (ES) 811.2652 ([M + Na]+,
C44H48FeN2NaO8 requires 811.2653), 789 (3%, [M + H]+), 806
(100, [M + NH4]+), 811 (67, [M + Na]+).
N1, N3-Dihexyl-5-ferrocenylisophthalamide (3). Ferrocenebo-
ronic acid (232 mg, 1.00 mmol) was added to DME (9 mL) in a
20 mL microwave vial (containing a stirring bar). To this was added
2 (458 mg, 1.00 mmol), then 3 M NaOH(aq) solution (1 mL). This
mixture was then degassed thoroughly for 20 min with nitrogen.
PdCl2(dppf) (7 mg, 0.01 mmol) was then added, the microwave vial
capped, and the vial subjected to microwave irradiation at 150 ◦C
for 30 min. The reaction mixture was then diluted with CHCl3
(100 mL) and H2O (25 mL). The organic layer was separated and
washed with H2O (3 ¥ 50 mL), dried over MgSO4, solvent removed
in vacuo and then purified by silica gel column chromatography
(hexane–EtOAc 1 : 0 to 2 : 1) to yield compound 3 as a dark orange
solid (303 mg, 59%). Mp = 68–70 ◦C; dH(300 MHz, CDCl3) 7.97
N1,
N3-Bis(2-(4-benzyloxy)phenoxy)ethyl)-5-iodoisophthal-
amide (7). 5-Iodoisopthalic acid (1.55 g, 5.32 mmol) was
suspended in SOCl2 (20 mL) and refluxed for 16 h under a drying
tube. The excess SOCl2 was removed by distillation, and the
crude diacid chloride (a brown oil) was then added in dry CH2Cl2
(75 mL), to a solution of 2-(4-benzyloxy)phenoxy)ethanamine 6
(2.59 g, 10.6 mmol) and NEt3 (2.69 g, ~ 4 mL, 26.6 mmol) in dry
CH2Cl2 (75 mL) at 0 ◦C, and then stirred at room temperature for
1 h under a nitrogen atmosphere. The reaction mixture was then
washed with 10% HCl(aq) (3 ¥ 150 mL), sat. NaHCO3 (150 mL) and
brine (150 mL), dried (MgSO4), and the solvent removed in vacuo.
The residue was subjected to silica gel column chromatography
(CH2Cl2–CH3OH 98 : 2), and then the resulting solid washed with
EtOAc to give 7 as a white solid (1.83 g, 46%). Mp = 160 ◦C;
4
(2H, d, J = 1.5 Hz, isophthalamide ArH4 & H6), 7.87 (1H, t,
3
4J = 1.5 Hz, isophthalamide ArH2), 6.32 (2H, t, J = 5.1 Hz,
4
dH(300 MHz, CDCl3) 8.22 (2H, d, J = 1.5 Hz, isophthalamide
NH), 4.72 (2H, t, 3J = 1.8 Hz, Fc CpH), 4.38 (2H, t, 3J = 1.8 Hz,
Fc CpH), 4.05 (5H, s, Fc Cp’H), 3.45–3.52 (4H, app quartet,
NHCH2CH2), 1.60–1.70 (4H, m, NHCH2CH2), 1.31–1.46 (12H,
m, 3 ¥ CH2), 0.89–0.93 (6H, m, CH3); dC(75.5 MHz, CDCl3)
167.0, 141.2, 135.1, 127.1, 121.9, 83.1, 69.7, 69.6, 66.6, 40.3, 31.5,
29.5, 26.7, 22.5, 14.0; m/z (ES) 517.2513 ([M + H]+, C30H41FeN2O2
requires 517.2517), 517 (100%, [M + H]+), 539 (19, [M + Na]+),
549 (31, [M + CH3OH + H]+), 571 (14, [M + CH3OH + Na]+).
ArH4 & H6), 8.11 (1H, t, J = 1.5 Hz, isophthalamide ArH2),
4
7.32–7.44 (10H, m, benzyl ArH), 6.83–6.93 (8H, m, hydroquinone
ArH), 6.69 (2H, t, J = 5.6 Hz, NH), 5.02 (4H, s, CH2), 4.10
3
(4H, t, 3J = 5.0 Hz, OCH2), 3.82–3.87 (4H, app. quartet, NCH2);
dC(75 MHz, d6-DMSO) 164.6, 152.6, 152.5, 138.1, 137.3, 136.3,
128.4, 127.7, 127.6, 126.0, 115.7, 115.4, 94.6, 69.2, 66.3 (1 peak
missing CNH - coincidental with solvent); m/z (ES) 765.1427
([M + Na]+, C38H35IN2NaO6 requires 765.1432), 801 (100%,
[M + CH3CN + NH4]+ - only assignable peak observed in low
resolution mass spectrum.
N1, N3-Bis(2-(4-(2-(allyloxy)ethoxy)phenoxy)ethyl-5-ferroce-
nylisophthalamide (5).
N1, N3-Bis(2-(4-benzyloxy)phenoxy)ethyl)-5-ferrocenylisoph-
thalamide (8). Ferroceneboronic acid (230 mg, 1.00 mmol) was
added to DME (9 mL) in a 20 mL microwave vial (containing
a stirring bar). To this was added 6 (743 mg, 1.00 mmol),
then 3 M NaOH(aq) solution (1 mL). This mixture was then
degassed thoroughly for 20 min with nitrogen. PdCl2(dppf) (7 mg,
0.01 mmol) was then added, the microwave v◦ial capped, and the
vial subjected to microwave radiation at 150 C for 30 min. The
reaction mixture was then diluted with CHCl3 (100 mL) and H2O
(25 mL). The organic layer was separated, washed with H2O
(3 ¥ 50 mL), and dried over MgSO4. The solvent was removed
in vacuo and then purified by silica gel column chromatography
(CH2Cl2: CH3OH 99 : 1) to yield 8 as a foaming orange solid
(303 mg, 59%). Mp: phase transitions at 68 ◦C and 120 ◦C;
Route A. Ferroceneboronic acid (230 mg, 1.00 mmol) was
added to DME (9 mL) in a 20 mL microwave vial (containing
stirring bar). To this was added iodo-arene compound 4 (731 mg,
1.00 mmol), then 3 M NaOH(aq) solution (1 mL). This mixture was
then degassed thoroughly for 20 min with nitrogen. PdCl2(dppf)
(7 mg, 0.01 mmol) was then added, the microwave via◦l capped,
and the vial subjected to microwave irradiation at 150 C for 30
min. The reaction mixture was then diluted with CHCl3 (100 mL)
and H2O (25 mL). The organic layer was separated, washed with
H2O (3 ¥ 50 mL) and dried over MgSO4, the solvent removed
in vacuo and then purified by silica gel column chromatography
(hexane–EtOAc 1 : 1 to 1 : 2) to yield 5 as an orange oil (156 mg,
20%).
Route B. Diphenol compound 9 (250 mg, 0.40 mmol), 2-
(allyloxy)ethyl 4-methylbenzenesulfonate (207 mg, 0.81 mmol)
and K2CO3 (123 mg, 0.89 mmol) were suspended in dry CH3CN
(15 mL) and heated under a nitrogen atmosphere for 60 h. The
reaction was cooled to room temperature, filtered and the solvent
removed in vacuo. The residue was dissolved in CH2Cl2, filtered
and then dried (MgSO4), the solvent removed in vacuo, and the
4
dH(300 MHz, CDCl3) 8.00 (2H, d, J = 1.5 Hz, isophthalamide
4
ArH4 & H6), 7.90 (1H, t, J = 1.5 Hz, isophthalamide ArH2),
7.32–7.44 (10H, m, benzyl ArH), 6.86–6.94 (8H, m, hydroqunione
3
ArH), 6.71–6.75 (2H, t, J = 5.7 Hz, NH), 5.02 (4H, s, CH2),
4.72–4.73 (2H, m, Fc CpH), 4.38–4.39 (2H, m, 2H, Fc CpH),
4.13–4.16 (4H, m, OCH2), 4.04 (5H, s, Fc Cp’H), 3.87–3.92 (4H,
98 | Org. Biomol. Chem., 2011, 9, 92–100
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app. quartet, NCH2); dC(75 MHz, CDCl3) 167.1, 153.3, 152.7,
141.4, 137.1, 134.8, 128.5, 127.9, 127.4, 122.1, 115.9, 115.4, 82.9,
70.6, 69.7, 69.7 (sic), 67.2, 66.7, 39.8. (1 ArC peak missing); m/z
(ES) 823.2436 ([M + Na]+, C48H44FeN2NaO6 requires 823.2442),
823 (7%, [M + Na]+), 859 (100, [M + CH3CN + Na]+).
ArH2 & ArH4 & ArH6), 7.61 (4H, d, 3J = 8.8 Hz, stopper ArH),
7.08–7.29 (32H, m, stopper ArH & isophthalamide NH), 6.48
(4H, t, 3J = 8.9 Hz, hydroquinone ArH), 6.37 (4H, t, 3J = 8.9 Hz,
hydroquinone ArH), 5.98 (2H br s, CH CH), 4.73 (2H, s, Fc
CpH), 4.37 (2H, s, Fc CpH), 4.31 (3H, s, N+CH3) 4.04–4.06 (9H,
3
m, Fc Cp’H & CH2) 3.93 (4H, t, J = 4.4 Hz, CH2), 3.86 (4H,
N1, N3-Bis(2-(4-hydroxyphenoxy)ethyl)-5-ferrocenylisophthal-
amide (9). To a solution of 8 (400 mg, 0.50 mmol) dissolved
in CHCl3–CH3OH (1 : 1, 20 mL) was added 10% Pd/C (10% by
wt, 40 mg), and the reaction was stirred under an atmosphere of
m, CH2), 3.81 (4H, m, CH2) 3.70–3.72 (4H, m, CH2), 1.31 (s,
36H, (CH3)3); dC(125.8 MHz, CDCl3) 167.0, 158.3, 152.8, 152.0,
148.6, 146.8, 145.3, 144.0, 143.4, 141.8, 141.3, 134.3, 134.3 (sic),
134.1, 132.0, 131.0, 130.6, 130.4, 128.5, 127.4, 125.9, 124.4, 121.6,
120.1, 115.5, 114.7, 83.2, 70.8, 69.7, 69.5, 69.3, 67.7, 66.9, 66.8,
63.9, 49.6, 39.7, 34.3, 31.4; dF(282.4 MHz, CDCl3) -69.9 (d, 1J =
714 Hz, PF6); dP(121.5 MHz, CDCl3) -143.9 (septet, 1J = 714 Hz,
R
H2 for 16 h. The reaction mixture was filtered through Celiteꢀ,
the solvent removed in vacuo, to leave the product as a foaming
orange solid (310 mg, quant.). Mp > 148 ◦C (dec.); dH(300 MHz,
d6-DMSO) 8.94 (2H, s, OH), 8.87 (2H, t, 3J = 5.6 Hz, NH), 8.20
(1H, t, 4J = 1.5 Hz, isophthalamide ArH2), 8.13 (2H, d, 4J = 1.5 Hz,
isophthalamide ArH4 & H6), 6.65–6.82 (8H, m, hydroquinone
ArH), 4.93 (2H, t, 3J = 1.9 Hz, Fc CpH), 4.43 (2H, t, 3J = 1.9 Hz,
Fc CpH), 4.02–4.07 (9H, m, Fc Cp’H & OCH2), 3.60–3.66 (4H,
app. quartet, NCH2); dC(75 MHz, d6-DMSO) 166.0, 151.4, 151.2,
139.9, 134.6, 126.7, 124.1, 115.8, 115.5, 83.4, 69.5, 69.4, 66.6, 66.6
(sic) (1 peak missing CNH - coincidental with solvent); m/z (ES)
643.1504 ([M + Na]+, C34H32FeN2NaO6 requires 643.1502), 643
(5%, [M + Na]+), 679 (100, [M + CH3CN + NH4]+). In addition,
619 (100%, [M - H]-), 655 (43, [M + Cl]-) observed in negative
polarity mass spectrum.
PF6 ); m/z (ES) 1800.8605 ([M - PF6]+, C116H122FeN5O10 requires
-
1800.8541), 1801 (100%, [M - PF6]+).
Acknowledgements
We wish to thank the EPSRC for a DTA studentship (N. H. E.),
Johnson-Matthey for the loan of palladium catalysts, and Dr J. J.
Davis (University of Oxford) for use of electrochemical equipment.
Notes and References
1 For general reviews on rotaxanes and catenanes see: (a) T. Takata, N.
Kihara and Y. Furusho, Adv. Poly. Sci., 2004, 171, 1; (b) J.-P. Collin,
V. Hertz and J.-P. Sauvage, Top. Curr. Chem., 2005, 262, 29; (c) F. H.
Huang and H. W. Gibson, Prog. Polym. Sci., 2005, 30, 982; (d) G.
Wenz, B.-H. Han and A. Mu¨ller, Chem. Rev., 2006, 106, 782; (e) M.
D. Lankshear and P. D. Beer, Acc. Chem. Res., 2007, 40, 657; (f) K.
E. Griffiths and J. F. Stoddart, Pure Appl. Chem., 2008, 80, 485; (g) A.
Harada, A. Hashidzume, H. Yamaguchi and Y. Takashima, Chem.
Rev., 2009, 109, 5974; (h) J. J. Gassensmith, J. M. Baumes and B. D.
Smith, Chem. Commun., 2009, 6329; (i) J. D. Crowley, S. M. Goldup,
A.-L. Lee, D. A. Leigh and R. T. McBurney, Chem. Soc. Rev., 2009,
38, 1530; (j) Z. Niu and H. W. Gibson, Chem. Rev., 2009, 109, 6024;
(k) For a comprehensive review on the nanotechnological application
of interlocked molecules see: E. R. Kay, D. A. Leigh and F. Zerbetto,
Angew. Chem., Int. Ed., 2007, 46, 72.
Chloride salt of rotaxane (1+Cl-). Macrocycle precursor 5
(81 mg, 0.10 mmol) and 10+Cl- (110 mg, 0.10 mmol) were added
to dry CH2Cl2 and stirred for 30 min under a nitrogen atmosphere.
Grubbs 2nd generation catalyst (8.1 mg) was added, stirred under
a constant flow of nitrogen for 16 h. The reaction solvent was
removed in vacuo, and after purification by two prep silica gel
TLC plates (CH2Cl2–CH3OH 96 : 4, then EtOAc), rotaxane 1+Cl-
was isolated as an orange solid (48 mg, 25%). Mp > 230 ◦C
(dec.); dH(300 MHz, CDCl3): 10.30 (2H, s, py NH), 9.68 (1H,
s, pyridinium ArH4), 9.25 (2H, s, pyridinium ArH2 & ArH6), 8.77
(1H, s, isophthalamide ArH2), 8.55 (2H, s, isophthalamide NH),
2 M. J. Chmielewski, J. J. Davis and P. D. Beer, Org. Biomol. Chem., 2009,
7, 415.
3
8.26 (2H, s, isophthalamide ArH4 & ArH6), 7.84 (4H, d, J =
3 Examples of cation-binding rotaxanes: (a) K. Hiratani, M. Kaneyama,
Y. Nagawa, E. Koyama and M. Kanesato, J. Am. Chem. Soc., 2004,
126, 13568; (b) N. C. Chen, P. Y. Huang, C. C. Lau, Y. H. Liu, Y. Wang,
S. M. Peng and S. H. Chiu, Chem. Commun., 2007, 4122; (c) S. S. Zhu,
P. J. Carroll and T. M. Swager, J. Am. Chem. Soc., 1996, 118, 8713;
(d) S. S. Zhu and T. M. Swager, J. Am. Chem. Soc., 1997, 119, 12568.
4 Examples of anion-binding rotaxanes: (a) J. A. Wisner, P. D. Beer, M.
G. B. Drew and M. R. Sambrook, J. Am. Chem. Soc., 2002, 124, 12469;
(b) D. Curiel and P. D. Beer, Chem. Commun., 2005, 1909; (c) M. R.
Sambrook, P. D. Beer, M. D. Lankshear, R. F. Ludlow and J. A. Wisner,
Org. Biomol. Chem., 2006, 4, 1529; (d) S. R. Bayly, T. M. Gray, M. J.
Chmielewski, J. J. Davis and P. D. Beer, Chem. Commun., 2007, 2234;
(e) L. M. Hancock and P. D. Beer, Chem.–Eur. J., 2009, 15, 42; (f) L.
Y. Zhao, J. J. Davis, K. M. Mullen, M. J. Chmielewski, R. M. J. Jacobs,
A. Brown and P. D. Beer, Langmuir, 2009, 25, 2935; (g) A. Brown, K.
M. Mullen, J. Ryu, M. J. Chmielweski, S. M. Santos, V. Felix, A. L.
Thompson, J. E. Warren, S. I. Pascu and P. D. Beer, J. Am. Chem. Soc.,
2009, 131, 4937; (h) K. M. Mullen, J. Mercurio, C. J. Serpell and P. D.
Beer, Angew. Chem., Int. Ed., 2009, 48, 4781; (i) A. J. McConnell, C. J.
Serpell, A. L. Thompson, D. R. Allan and P. D. Beer, Chem.–Eur. J.,
2010, 16, 1256; (j) J. J. Gassensmith, S. Matthys, J. J. Lee, A. Wojcik, P.
V. Kamat and B. D. Smith, Chem.–Eur. J., 2010, 16, 2916.
8.8 Hz, stopper NHArH), 7.06–7.26 (30H, m, stopper ArH), 6.45
(4H, d, 3J = 8.9 Hz, hydroquinone ArH), 6.20 (4H, d, 3J = 8.9 Hz,
hydroquinone ArH), 5.96 (2H, br s, CH CH), 4.68 (2H, app s, Fc
CpH), 4.32 (5H, app s, Fc CpH & N+CH3), 4.19 (4H, br s, CH2),
4.05 (app s, 4H, CH2), 4.00 (5H, s, Fc Cp’H), 3.75–3.85 (12H, m,
3 ¥ CH2), 1.32 (36H, s, (CH3)3); dC(125.8 MHz, CDCl3) 168.9,
158.1, 153.4, 151.9, 148.4, 146.9, 145.2, 144.8, 143.5, 140.4, 139.4,
134.8, 134.0, 133.4, 131.8, 131.1, 130.6, 129.9, 129.0, 127.4, 125.8,
124.3, 122.1, 120.4, 114.8, 114.5, 71.0, 69.3, 68.0, 66.1, 63.8, 48.8,
40.6, 34.3, 31.4 (in addition evidence of broad peaks attributed to
the four CpC); m/z (ES) 1800.8585 ([M - Cl]+, C116H122FeN5O10
requires 1800.8541), 1801 (100%, [M - Cl]+).
-
Hexafluorophosphate salt of rotaxane (1+PF6 ). Rotaxane
1+Cl- (72 mg, 0.039 mmol) was dissolved in CHCl3 (15 mL), and
then vigorously shaken with 0.1 M NH4PF6 (10 ¥ 10 mL), then
washed with H2O (3 ¥ 10 mL). The organic layer was separated,
then dried over MgSO4, with the solvent subsequently removed
in vacuo to yield rotaxane 1+PF6- as a yellow-orange solid (59 mg,
78%). Mp > 220 ◦C (dec.); dH(300 MHz, CDCl3) 9.23 (2H, s,
pyridinium NH), 8.90 (1H, s, pyridinium ArH4), 8.54 (2H, s,
pyridinium ArH2 & ArH6), 8.19–8.21 (3H, m, isophthalamide
5 J. L. Sessler, P. A. Gale and W.-S. Cho, Anion Receptor Chemistry, RSC,
Cambridge, 2006.
6 Illustrative examples of ferrocene-containing anion receptors: (a) P.
D. Beer, Z. Chen, A. J. Goulden, A. Graydon, S. E. Stokes and T.
Wear, J. Chem. Soc., Chem. Commun., 1993, 1834; (b) P. D. Beer, A.
R. Graydon, A. O. M. Johnson and D. K. Smith, Inorg. Chem., 1997,
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36, 2112; (c) G. Denuault, P A. Gale, M. B. Hursthouse, M. E. Light
and C. N. Warriner, New J. Chem., 2002, 26, 811; (d) Y. Willener, K. A.
Joly, C. J. Moody and J. H. R. Tucker, J. Org. Chem., 2008, 73, 1225;
(e) F. Zapata, A. Caballero, A. Tarraga and P. Molina, J. Org. Chem.,
2010, 75, 162. For reviews see: (f) P. D. Beer and S. R. Bayly, Top. Curr.
Chem., 2005, 255, 125; (g) S. R. Bayly, P. D. Beer and G. Z. Chen, in
Angew. Chem., Int. Ed., 2007, 46, 3521; (c) Y. Suzuki, E. Chihara, A.
Takagi and K. Osakada, Dalton Trans., 2009, 9881.
9 During the course of this work another group published an article on
the synthesis and electrochemical anion recognition of a set of simple
acyclic 5-ferrocenylisophthalamides: W. Liu, H. Zheng, L. Du, B. Chen
and M. Song, Z. Anorg. Allg. Chem., 2010, 636, 236.
10 R. Knapp and M. Rehahn, J. Organomet. Chem., 1993, 452, 235.
11 M. J. Hynes, J. Chem. Soc., Dalton Trans., 1993, 311.
12 K. Kavallieratos, C. M. Bertao and R. H. Crabtree, J. Org. Chem., 1999,
64, 1675.
ˇ
Ferrocenes: Ligands, Materials and Biomolecules, ed. Petr Steˇpnicˇka,
Wiley, UK, 2008, ch. 8, pp 281–318.
7 (a) N. Kihara, M. Hashimoto and T. Takata, Org. Lett., 2004, 6, 1693;
(b) R. Isnin and A. E. Kaifer, J. Am. Chem. Soc., 1991, 113, 8188; (c) A.
C. Benniston and A. Harriman, Angew. Chem., Int. Ed. Engl., 1993, 32,
1459; (d) A. C. Benniston and A. Harriman, J. Am. Chem. Soc., 1995,
117, 5275.
8 (a) I. Willner, V. Pardo-Yissar, E. Katz and K. T. Ranjit, J. Electroanal.
Chem., 2001, 497, 172; (b) A. Mateo-Alonso, C. Ehli, G. M. A. Rahman,
D. M. Guldi, G. Fioravanti, M. Maraccio, F. Paolucci and M. Prato,
13 P. D. Beer, P. A. Gale and G. Z. Chen, J. Chem. Soc., Dalton Trans.,
1999, 1897.
14 A. Kraft, Liebigs Ann./Recl., 1997, 1463.
15 C. Goldenberg, R. Wandestrick, F. Binon and R. C Chorlier, Chim.
Ther., 1973, 8, 259.
16 H. D. Maynard and R. H. Grubbs, Macromolecules, 1999, 32, 6917.
100 | Org. Biomol. Chem., 2011, 9, 92–100
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