Synthesis of α-cyclodextrin [2]-rotaxanes using chlorotriazine capping reagents

Article abstract of DOI:10.1039/b802229a

Ten α-cyclodextrin [2]-rotaxanes have been prepared with alkane-, stilbene- and azobenzene-based axles, capped through nucleophilic substitution of either 2-chloro-4,6-dimethoxy-1,3,5-triazine or 2,4-dichloro-6-methoxy-1,3,5- triazine in aqueous solution, followed by further substitution of the remaining triazinyl chlorine in some cases when the latter capping reagent was used. In one case the rotaxane is a [c₂]-daisy chain obtained by double-capping the corresponding hermaphroditic cyclic dimer. One of the rotaxane azobenzene derivatives was shown to undergo photochemically-induced reversible interconversion between its trans- and cis-isomers, causing the cyclodextrin to move back and forth along the axle, and therefore behave as a molecular shuttle. The methodology is therefore shown to constitute a general and versatile approach for the construction of supramolecular species as the basis of photochemical molecular devices. The Royal Society of Chemistry.

Full text of DOI:10.1039/b802229a

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Synthesis of a-cyclodextrin [2]-rotaxanes using chlorotriazine capping
reagents
Ryan E. Dawson,a Subashani Maniam,a Stephen F. Lincolnb and Christopher J. Easton*a,c
Received 8th February 2008, Accepted 28th February 2008
First published as an Advance Article on the web 31st March 2008
DOI: 10.1039/b802229a
Ten a-cyclodextrin [2]-rotaxanes have been prepared with alkane-, stilbene- and azobenzene-based
axles, capped through nucleophilic substitution of either 2-chloro-4,6-dimethoxy-1,3,5-triazine or
2,4-dichloro-6-methoxy-1,3,5-triazine in aqueous solution, followed by further substitution of the
remaining triazinyl chlorine in some cases when the latter capping reagent was used. In one case the
rotaxane is a [c2]-daisy chain obtained by double-capping the corresponding hermaphroditic cyclic
dimer. One of the rotaxane azobenzene derivatives was shown to undergo photochemically-induced
reversible interconversion between its trans- and cis-isomers, causing the cyclodextrin to move back and
forth along the axle, and therefore behave as a molecular shuttle. The methodology is therefore shown
to constitute a general and versatile approach for the construction of supramolecular species as the
basis of photochemical molecular devices.
often been accomplished using 2,4,6-trinitrobenzenesulfonic acid
Introduction
as the capping reagent,27–34 but the product rotaxanes are either
[2]-Rotaxanes are suitable building blocks for the assembly of
photochemically inert or unstable, which severely compromises
supramolecular species, each consisting of a macrocycle threaded
on an axle that is capped or blocked with bulky end groups to
prevent the dissociation of the components.1 They are of interest
their utility as molecular devices. Here we report a range of
examples of the use of 2-chloro-4,6-dimethoxy-1,3,5-triazine (7)
and 2,4-dichloro-6-methoxy-1,3,5-triazine (13) as complementary
capping reagents for a-CD-based rotaxane synthesis, also through
as building blocks for the construction of nanotechnological
devices. Cyclodextrins (CDs) are well-suited as the macrocycles
nucleophilic substitution.
for rotaxane synthesis.2–6 The structures of a- and b-CD are shown
in Fig. 1. Their hydrophobic interiors and hydrophilic exteriors
promote the formation of inclusion complexes with hydrophobic
guests in aqueous solution. Capping each end of an encapsulated
guest then produces a [2]-rotaxane via what is termed the threading
method.7,8
At the outset of this study, Kunitake et al.,37 had already used
the bulky dichlorotriazine 2 to prepare the b-CD rotaxane 3,
which through reaction with aniline 4 afforded the derivative
5 (Scheme 1). The Anderson group38 had also employed 2,4,6-
trichloro-1,3,5-triazine to prepare a hexakis(2,3,6-tri-O-methyl)-
a-CD rotaxane, which had been further elaborated through
sequential displacement of the remaining triazinyl chlorines.
However, other chlorotriazines had not been studied, and it was
not clear if the chlorotriazines 7 and 13 would be effective blocking
reagents, reacting selectively with guests complexed by a-CD
rather than either the corresponding free guests, the nucleophilic
hydroxy groups of the CD or the water required to induce guest
complexation, particularly under the basic conditions necessary
to maintain the nucleophilic reactivity of the guest. The Anderson
group explained that they chose to use the termethylated a-CD in
order to prevent coupling between the trichlorotriazine and the
CD.
Fig. 1 Structures of a- and b-cyclodextrin (left) and their schematic
representation as a truncated cone (right).
Results and discussion
A variety of reactions have been utilised in the construction
of CD-based [2]-rotaxanes. These include metal coordination,9–12
Suzuki coupling,13–20 amide coupling,21–24 alkylation25,26 and nu-
cleophilic aromatic substitution.27–36 The last of these has most
In the event such processes did not complicate the synthesis
of rotaxanes using unmodified a-CD. In a typical procedure,
illustrated in Scheme 2, a solution of a-CD and the diamine
6 in 0.2 M carbonate buffer at pH 10 was stirred at room
temperature for 2 h, to allow inclusion complex formation, before
the chlorotriazine 7 was added and the mixture was stirred for a
further 12 h. Product formation was monitored by TLC, which
showed a component with an Rf value higher than that of a-CD,
aResearch School of Chemistry, The Australian National University, Can-
berra, ACT 0200, Australia. E-mail: easton@rsc.anu.edu.au
bSchool of Chemistry and Physics, The University of Adelaide, Adelaide, SA
5005, Australia
c ARC Centre of Excellence for Free Radical Chemistry and Biotechnology
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the diaminostilbene 1 instead of the diamine 6. In the latter case,
triethylamine was used as an alternative to carbonate to control
the pH of the reaction mixture, and the product was isolated using
HPLC.
The dichlorotriazine 13 is understood to be generally more
reactive and less selective towards nucleophilic substitution than
the monochloride 7.39,40 Nevertheless, it reacted with the diaminos-
tilbene 1 and the diaminoazobenzene 12 in the presence of a-CD,
under conditions analogous to those described above, to give the
rotaxanes 14a and 14b, in yields of 20% and 19%, respectively
(Scheme 3). The labile chlorines of the rotaxanes 14a and 14b
provide versatility for further functionalisation, as exemplified in
the earlier reports of Kunitake et al.,37 and the Anderson group.38
Accordingly, reactions with aniline 15a and 1,3-diaminopropane
15b gave the rotaxanes 16a and 16b, in yields of 33% and 76%,
respectively. Under closely related conditions, the diamine 11
reacted with the dichlorotriazine 13 in the presence of a-CD to
give a 5% yield of the rotaxane 9b, which reacted with allylamine
to give the rotaxane 9c in 59% yield.
Scheme 1 Formation of the triazine-capped b-cyclodextrin [2]-rotaxanes
3 and 5 as reported by Kunitake et al.37
As the final example of a methoxytriazine-capped rotaxane,
treatment of the hermaphroditic29,41 stilbenyl-a-CD 1742 with the
dichlorotriazine 13 afforded the [c2]-daisy chain 18 in 13% yield
(Scheme 4). The dimeric nature of this species was established
using mass spectrometry and the symmetry inherent in the cyclic
structure, as distinct from the corresponding linear daisy chain,
was apparent from the simplicity of the 1D 1H NMR spectrum.
The rotaxanes 8, 9a–c, 10, 14a,b, 16a,b and 18 were fully charac-
terised. In each case, 13C and 1D 1H NMR spectroscopy were used
to confirm the identity of the macrocyclic and axle components,
which were shown by TLC, HPLC and mass spectrometry to
be physically interlocked as a supramolecular entity and unable
to dissociate. The preferred conformations of the rotaxanes in
MeOH-d4 and DMSO-d6 were determined using DQCOSY and
ROESY 1H NMR spectroscopy. With the rotaxanes 9a–c, 10,
14a,b, 16a,b and 18, NOE interactions in the ROESY spectra show
Scheme 2 Synthesis of the rotaxane 8.
and having both the UV absorbance of an aromatic compound
and the characteristic pink colouration of a CD on exposure
to acidic naphthalene-1,3-diol.28,29 This material was isolated by
chromatography on a Diaion HP-20 column and identified as the
rotaxane 8, which was obtained in 25% yield.
In a similar manner, the rotaxanes 9a and 10 were prepared in
yields of 31% and 5%, respectively, using the azobenzene 11 and
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Fig. 2 A section of the 500 MHz 2D ROESY NMR spectrum of
the [2]-rotaxane 9a in MeOH-d4 at 25 ◦C, showing crosspeaks between
azobenzene and cyclodextrin proton signals.
Scheme 3 Synthesis of the rotaxanes 14a,b and 16a,b.
Scheme 4 Synthesis of the rotaxane 18.
that the CD is located over the azobenzene or stilbene moiety, as
illustrated in Fig. 2 and 3 for the rotaxanes 9a and 14a, respectively.
One of the objectives of the current work was to estab-
lish chemistry to underpin the development of photochemical
molecular devices. As a preliminary assessment of the utility of
methoxytriaxine-capped rotaxanes in this area, the photochem-
ical behaviour of the azobenzene derivative 9a was examined.
Generally, stilbenes and azobenzenes can undergo reversible inter-
conversion between their trans- and cis-isomers upon irradiation,
and the direction is determined by the wavelength of incident
Fig. 3 A section of the 500 MHz 2D ROESY NMR spectrum of the
[2]-rotaxane 14a in DMSO-d6 at 25 ◦C, showing crosspeaks between
stilbene and cyclodextrin proton signals.
light.43–46 This has been exploited in the development of CD-based
molecular shuttles.15,35,36
Irradiation at 350 nm of a dilute aqueous solution of the
rotaxane 9a afforded a 60 : 40 mixture of the starting material and
the cis-isomer 19, at the photostationary state, as determined using
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HPLC and UV–visible spectroscopy. When solutions containing
the cis-rotaxane 19 were irradiated at 420 nm or left standing
under normal laboratory lighting, complete conversion back to
the trans-isomer 9a was observed. A sample enriched in the cis-
rotaxane 19 was isolated through HPLC. Its ROESY spectrum
recorded in MeOH-d4 shows no NOE interactions between CD
and azobenzene protons, indicating that the CD moves as a
result of the photoisomerisation. This is consistent with a-CD
less readily accommodating a cis-azobenzene moiety than the
trans-isomer.15,35,36 The central methylene protons of the propyl
groups of the rotaxane 19 give rise to resonances at d 1.84 and
2.06 ppm in the 1D 1H NMR spectrum, which are distinct due to
the asymmetry imposed by the CD. These show NOE interactions
with CD protons, indicating that at various times the CD is
located over each propyl group. If the CD did not move between
these two locations, there would be two distinct compounds with
distinguishable spectra. Therefore, instead, it is logical to assume
that the CD moves from one to the other propyl group, over the
azobenzene moiety, on the NMR time-scale. The operation of the
rotaxane 9a as a photochemical molecular shuttle is therefore as
illustrated in Fig. 4.
in the rotaxanes may be displaced through further nucleophilic
aromatic substitution, providing synthetic versatility, and the
methoxytriazine-capped rotaxanes appear to be suitable for the
construction of photochemical molecular devices.
Experimental
General
NMR spectra were recorded on either a Varian Gemini 300
spectrometer or a Varian Inova 500 spectrometer. Chemical
shift (d) values are given in ppm and coupling constants (J)
are given in Hertz. MeOH-d4 with an isotopic purity of 99.8%
was purchased from Apollo Scientific Ltd. DMSO-d6 with an
isotopic purity of 99.8% and CDCl3 with an isotopic purity of
99.8% were purchased from Cambridge Isotope Laboratories
Inc. Electrospray ionisation (ESI) mass spectra were recorded
using either a Micromass-Waters LC-ZMD single quadrupole
liquid chromatograph mass spectrometer or a Bruker Apex 4.7
T FTICR mass spectrometer. Elemental analyses were performed
by the Australian National University Analytical Services Unit
based at the Research School of Chemistry. Melting points were
determined on a Kofler hot-stage melting point apparatus under
a Reichert microscope and are uncorrected. High performance
liquid chromatography (HPLC) was performed using a Waters
600 Controller with a Waters 717 plus Autosampler, a Waters
2996 Photodiode Array Detector running with Empower Pro
Empower 2 software, and a Waters Fraction Collector III. Thin
layer chromatography (TLC) was carried out on alumina backed
plates coated with Merck silica gel F254. Developed plates were
visualised using ultraviolet light and/or by dipping the plates
into a solution of 0.1% naphthalene-1,3-diol in 200 : 157 : 43
v/v/v ethanol–water–H2SO4, followed by heating with a heat
gun.28,29 a-CD was acquired from Nihon Shokuhin Kako Co.,
Japan, in 99.1% purity and was dried over P2O5 under reduced
pressure to constant weight before use. Diaion HP-20 resin was
purchased from Supelco, PA. All other starting materials, solvents
and reagents were commercially available.
[N,Nꢀ-Bis(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,12-
diaminododecane]-[a-cyclodextrin]-[2]-[rotaxane] (8)
A mixture of a-CD (1.80 g, 1.85 mmol) and the diamine 6 (77 mg,
0.38 mmol) in 0.2 mol dm−3 carbonate buffer (pH 10, 25 cm3)
was stirred at room temperature for 2 h, before the triazine 7
(0.27 g, 1.55 mmol) was added and that mixture was stirred at
room temperature for an additional 12 h. The resulting solution
was washed with EtOAc (5 × 25 cm3) and concentrated under
reduced pressure. The residue dissolved in water (40 cm3) and
the solution was applied to a Diaion HP-20 column (310 ×
25 mm). The column was eluted with water (ca. 3.0 dm3) until no
more unreacted a-CD was detected by TLC. A water–methanol
gradient was then applied to the column and fractions eluting with
30% aqueous methanol were combined and concentrated under
reduced pressure, to give the title compound 8 as a colourless
powder (140 mg, 25%); mp 203–204 ◦C (dec.); dH (500 MHz,
MeOH-d4) 4.98 (6H, d, J 3.5), 4.02–3.98 (6H, m), 3.94 (6H, s), 3.92
(6H, s), 3.88–3.86 (12H, m), 3.78–3.74 (6H, m), 3.59–3.51 (12H,
m), 3.42–3.37 (4H, m), 1.71–1.60 (4H, m), 1.57–1.34 (16H, m); dC
Fig. 4 Operation of the rotaxane 9a as a photochemical molecular shuttle.
It follows that methoxytriazines are effective blocking groups for
a-CD-based [2]-rotaxanes with alkane-, stilbene- and azobenzene-
based axles. The capping reagents, 2-chloro-4,6-dimethoxy-1,3,5-
triazine (7) and 2,4-dichloro-6-methoxy-1,3,5-triazine (13), both
show the necessary selectivity to react with nucleophilic guests
complexed by a-CD in aqueous solution, irrespective of whether
the guest is an aliphatic or a less-reactive aromatic diamine. When
the dichlorotriazine 13 is used, the triazinyl chlorines remaining
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(75.5 MHz, MeOH-d4) 172.8, 172.2, 168.8, 168.5, 103.9, 83.3, 75.1,
73.7, 73.4, 61.4, 55.5, 55.2(3), 55.2, 55.1, 42.1, 42.0, 32.4, 32.3, 32.0,
31.9, 31.7, 31.0, 30.6, 30.3, 29.0, 28.2; m/z (ESI, positive) 1451
(M + H+); TLC (5 : 4 : 3 v/v/v, n-BuOH–EtOH–H2O) Rf 0.45
(relative to the solvent front), 1.7 (relative to a-CD); elemental
analysis: found: C, 45.87; H, 6.44; N, 7.11. C58H98N8O34·3H2O
requires C, 46.27; H, 6.96; N, 7.44%.
(2H, d, J 8.0), 5.34–5.33 (6H, m), 5.31–5.30 (6H, m), 4.69 (6H,
d, J 3.3), 4.39–4.37 (6H, m), 3.84–3.80 (6H, m), 3.55–3.35 (24H,
m), 3.25–3.24 (6H, m), 3.20–3.18 (14H, m), 1.86–1.79 (4H, m);
dC (75.5 MHz, MeOH-d4) 172.5, 172.0, 171.9, 171.2, 170.0, 169.1,
168.4, 154.9, 154.7, 139.2, 138.6, 129.8, 129.1, 126.2, 126.1, 124.2,
103.9, 83.1, 75.0, 73.8, 73.4, 61.7, 55.9, 55.7, 42.1, 39.7, 30.1,
30.0; m/z (ESI, positive) 1642 [(M + H+), 10], 1664 [(M + Na+),
100]; TLC (5 : 4 : 3 : 2 v/v/v/v, i-PrOH–EtOH–H2O–AcOH)
Rf 0.75 (relative to the solvent front), 1.30 (relative to a-CD);
HPLC tR 6.5 min [Luna Phenomenex column (250 × 10 mm),
eluting with H2O–MeCN–TFA (70 : 30 : 0.1, v/v/v), flow rate
3.0 cm3 min−1]; elemental analysis: found: C, 44.44; H, 5.74; N,
9.95. C64H90Cl2N12O34.5H2O requires C, 44.37; H, 5.82; N, 9.70%.
[(E)-N,Nꢀ-Bis(3-(4,6-dimethoxy-1,3,5-triazin-2-ylamino)propyl)-
4,4ꢀ-azobenzenedicarboxamide]-[a-cyclodextrin]-[2]-
[rotaxane] (9a)
A mixture of a-CD (3.0 g, 3.09 mmol) and the diamine 11 (0.10 g,
0.26 mmol) in 0.2 mol dm−3 carbonate buffer (pH 10, 25 cm3)
was stirred at room temperature for 2 h, before the triazine 7
(0.27 g, 1.55 mmol) was added and that mixture was stirred at
room temperature for an additional 12 h. The resulting solution
was washed with EtOAc (5 × 25 cm3) and concentrated under
reduced pressure. The residue dissolved in water (40 cm3) and
the solution was applied to a Diaion HP-20 column (310 ×
25 mm). The column was eluted with water (ca. 3.0 dm3) until no
more unreacted a-CD was detected by TLC. A water–methanol
gradient was then applied to the column and fractions eluting with
40% aqueous methanol were combined and concentrated under
reduced pressure, to give the title compound 9a as an orange
powder (131 mg, 31%); mp 226–228 ◦C (dec.); dH (500 MHz,
MeOH-d4) 8.54 (2H, d, J 8.5), 8.12 (2H, d, J 8.5), 8.10 (2H, d,
J 8.5), 7.96 (2H, d, J 8.5), 4.88 (6H, br), 3.97–3.92 (12H, m),
3.79–3.77 (6H, m), 3.74–3.70 (12H, m), 3.55–3.49 (20H, m), 3.44–
3.41 (6H, m), 2.02–1.95 (4H, m); dC (75.5 MHz, MeOH-d4) 185.1,
169.4, 169.1, 129.6, 128.8, 125.8, 123.9, 103.7, 82.8, 74.7, 73.5,
73.1, 61.3, 54.8, 39.2, 34.8, 30.0; m/z (ESI, positive) 1633 [(M +
H+), 80], 1655 [(M + Na+), 100]; HPLC tR 2.98 min [YMC-PACK
ODS-AQ column (250 × 10 mm), eluting with H2O–MeCN (3 : 1,
v/v), flow rate 3.0 cm3 min−1]; TLC (5 : 4 : 3 : 2 v/v/v/v, i-PrOH–
EtOH–H2O–AcOH) Rf 0.75 (relative to the solvent front), 1.20
(relative to a-CD); elemental analysis: found: C, 44.85; H, 6.30; N,
9.10. C66H96N12O36·8H2O requires C, 44.59; H, 6.35; N, 9.46%.
[(E)-N,Nꢀ-Bis(3-(4-allylamino-6-methoxy-1,3,5-triazin-2-
ylamino)propyl)-4,4ꢀ-azobenzenedicarboxamide]-[a-cyclodextrin]-
[2]-[rotaxane] (9c)
To a solution of the [2]-rotaxane 9b (20 mg, 10 lmol) in anhydrous
DMF (1 cm3), allylamine (1 cm3) was added, and the mixture
was left stirring for 10 h at room temperature, before it was
added dropwise to acetone (10 cm3). The resultant precipitate was
collected by centrifugation and resuspended in acetone (15 cm3).
The solid was collected, again by centrifugation. HPLC of this
material gave the title compound 9c as an orange powder (12 mg,
59%); mp 270–274 ◦C (dec.); dH (500 MHz, MeOH-d4) 8.58–8.52
(2H, m), 8.13–8.09 (4H, m), 7.99–7.96 (2H, d, J 8.0), 5.21 (2H, m),
5.09 (4H, m), 4.98 (6H, m), 4.02 (3H, s), 3.93 (3H, s), 3.78–3.70
(20H, m), 3.68–3.56 (16H, m), 3.55–3.50 (6H, m), 3.52–3.50 (6H,
m), 2.16–1.97 (4H, m); dC (75.5 MHz, MeOH-d4) 178.3, 172.1,
168.2, 154.9, 136.4, 129.9, 129.1, 124.2, 115.8, 103.9, 83.1, 75.0,
73.8, 73.3, 61.7, 54.3, 44.0, 39.2, 35.4, 30.5; m/z (ESI, positive)
1683 ([M + H+), 100], 1705 [(M +Na+), 50]; TLC (5 : 4 : 3 :
2 v/v/v/v, i-PrOH–EtOH–H2O–AcOH) Rf 0.85 (relative to the
solvent front), 1.15 (relative to a-CD); HPLC tR 9.2 min [Luna
Phenomenex column (250 × 10 mm), eluting with H2O–MeCN–
TFA (85 : 15 : 0.1, v/v/v), flow rate 3.0 cm3 min−1]; elemental
analysis: found: C, 45.47; H, 6.28; N, 10.53. C70H102N14O34.9H2O
requires C, 45.55; H, 6.55; N, 10.62%.
[(E)-N,Nꢀ-Bis(3-(4-chloro-6-methoxy-1,3,5-triazin-2-
ylamino)propyl)-4,4ꢀ-azobenzenedicarboxamide]-[a-cyclodextrin]-
[2]-[rotaxane] (9b)
[(E)-N,Nꢀ-Bis(4,6-dimethoxy-1,3,5-triazin-2-yl)-
4,4ꢀ-diaminostilbene]-[a-cyclodextrin]-[2]-[rotaxane] (10)
A mixture of a-CD (3.0 g, 3.09 mmol) and the diamine 11 (0.10 g,
0.26 mmol) in water (25 cm3) adjusted to pH 10 with triethylamine
was stirred at room temperature for 2 h, before the triazine 13
(0.34 g, 1.88 mmol) was added and that mixture was stirred at
room temperature for an additional 12 h. The resulting solution
was washed with EtOAc (5 × 25 cm3) and concentrated under
reduced pressure. The residue dissolved in water (40 cm3) and the
solution was applied to a Diaion HP-20 column (310 × 25 mm).
The column was eluted with water (ca. 3.0 dm3) until no more
unreacted a-CD was detected by TLC. A water–methanol gradient
was then applied to the column and fractions eluting with 20–
30% aqueous methanol were combined and concentrated under
reduced pressure. HPLC of the residue gave the titl◦e compound
9b as an orange powder (20 mg, 5%); mp 252–256 C (dec.); dH
(500 MHz, DMSO-d6) 8.80 (1H, t, J 4.5), 8.34 (2H, d, J 8.0),
8.07–8.06 (4H, m), 7.93 (2H, d, J 8.0), 7.95–7.90 (1H, m), 7.72
A mixture of a-CD (0.69 g, 0.71 mmol) and the stilbene 1 (50 mg,
0.24 mmol) in water (80 cm3) adjusted to pH 9 with triethylamine
was stirred at room temperature for 2 h, before the triazine 7
(88 mg, 0.50 mmol) was added and that mixture was stirred at
room temperature for an additional 17 h. The resulting solution
was washed with EtOAc (3 × 50 cm3) and concentrated under
reduced pressure. HPLC of the residue gave the title compound
10 as an colourless powder (17 mg, 5%); mp 264 ◦C (dec.); dH
(500 MHz, DMSO-d6) 10.23 (1H, s), 9.94 (1H, s), 7.75–7.78 (4H,
m), 7.74 (2H, d, J 8.0), 7.22 (2H, d, J 8.0), 6.98 (1H, d, J 16.0), 6.79
(1H, d, J 16.0), 5.42 (6H, s), 5.28 (6H, s), 4.75 (6H, d, J 2.5), 4.41
(6H, apparent t, J 5.5), 3.88–3.98 (12H, m), 3.70 (6H, apparent d, J
9.5), 3.65 (6H, apparent t, J 9.0), 3.59 (6H, m), 3.43 (6H, apparent
t, J 9.0), 3.30 (6H, m), 3.24 (6H, m); dC (125 MHz, DMSO-d6)
173.0–171.8 (br), 165.8, 165.7, 138.0, 137.7, 133.5, 131.4, 131.0,
127.5, 127.3, 125.8, 125.2, 120.1, 119.7, 102.1, 81.7, 73.2, 72.1, 71.8,
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61.0, 54.2–55.8 (br); m/z (ESI, positive) 1462 (M + H+); TLC (5 : 4 :
3 v/v/v, n-butanol–ethanol–water) Rf 0.55 (relative to the solvent
front), 1.15 (relative to a-CD); HPLC tR 13.6 min [YMC-PACK
ODS-AQ column (250 × 20 mm), eluting with H2O–MeCN (9 :
1, v/v), flow rate 10.0 cm3 min−1]; elemental analysis: found: C,
43.70; H, 6.13; N, 6.60. C60H84N8O34.10H2O requires C, 43.90; H,
6.39; N, 6.83%.
(90 mg, 0.50 mmol) was added and that mixture was stirred at
room temperature for an additional 17 h. The resulting solution
was washed with EtOAc (3 × 50 cm3) and concentrated under
reduced pressure. HPLC of the residue gave the titl◦e compound
14a as an colourless powder (69 mg, 20%); mp 265 C (dec.); dH
(500 MHz, DMSO-d6) 10.81 (1H, s), 10.62 (1H, s), 7.80 (2H, d, J
7.5), 7.76 (2H, d, J 7.5), 7.71 (2H, d, J 7.5), 7.27 (2H, d, J 7.5), 7.02
(1H, d, J 16.5), 6.83 (1H, d, J 16.5), 4.75 (6H, d, J 2.5), 4.04 (3H,
s), 4.00 (3H, s), 3.56–3.69 (18H, m), 3.43 (6H, apparent t, J 4.0),
3.29 (6H, m), 3.23 (6H, dd, J 3.0, 12.5); m/z (ESI, positive) 1492
(M + Na+); TLC (5 : 4 : 3 v/v/v, n-BuOH–EtOH–H2O) Rf 0.70
(relative to the solvent front), 1.80 (relative to a-CD); HPLC tR
10.8 min [YMC-PACK ODS-AQ column (250 × 20 mm), eluting
with H2O–MeCN (7 : 1, v/v), flow rate 10.0 cm3 min−1]; elemental
analysis: found: C, 42.87; H, 5.69; N, 6.61. C58H78Cl2N8O32·9H2O
requires C, 42.68; H, 5.93; N, 6.86%.
(E)-N,Nꢀ-Bis(3-aminopropyl)-4,4ꢀ-azobenzenedicarboxamide (11)
A solution of Boc2O (6.0 g, 28 mmol) in CHCl3 (38 cm3) was
added dropwise to a solution of 1,3-diaminopropane (138 cm3) in
CHCl3 (250 cm3) at 0 ◦C, then the mixture was allowed to warm
to room temperature and stirred for 2 h, before it was filtered
and the filtrate was concentrated under reduced pressure. The oily
residue was dissolved in EtOAc (125 cm3) and the solution was
washed with brine, dried (MgSO4) and allowed to evaporate over
2 weeks, to form N-(tert-butoxycarbonyl)-1,3-diaminopropane as
a colourless solid (2.4 g, 50%); mp 94–96 ◦C; dH (300 MHz, CDCl3)
4.93 (1H, s), 3.21–3.15 (2H, m), 2.76–2.71 (2H, m), 1.71 (9H, s),
1.63–1.54 (2H, m), 1.41 (2H, m); m/z (ESI, positive) 175 (M + H+).
(E)-4,4ꢀ-Azobenzenedicarboxylic acid (0.10 g, 0.37 mmol), N-
(tert-butoxycarbonyl)-1,3-diaminopropane (0.15 g, 0.88 mmol)
and BOP (0.39 g, 0.89 mmol) were dissolved in anhydrous DMF
(4 cm3). Triethylamine (0.13 cm3) was added and the mixture
was stirred for 12 h at room temperature. The resultant precip-
itate was separated by filtration and recrystallised from ethanol
to yield (E)-N,Nꢀ-bis(3-(tert-butoxycarbonylamino)propyl)-4,4ꢀ-
azobenze◦nedicarboxamide as an orange solid (0.20 g, 93%); mp
260–261 C (dec.); dH (300 MHz, DMSO-d6) 8.66 (2H, t, J 5.7),
8.05 (4H, d, J 8.0), 7.98 (4H, d, J 8.0), 6.85 (2H, t, J 5.5), 3.30–3.26
(4H, m), 3.01–2.95 (4H, m), 1.66–1.62 (4H, m), 1.37 (18H, s); dC
(75.5 MHz, DMSO-d6) 165.4, 155.7, 153.2, 137.1, 128.6, 122.6,
77.6, 37.8, 37.2, 29.6, 28.3; m/z (ESI, positive) 583 [(M + H+) 95],
605 [(M + Na+), 100]; elemental analysis: found: C, 61.51; H, 6.99;
N, 14.23. C30H42N6O6 requires C, 61.84; H, 7.26; N, 14.42%.
(E)-N,Nꢀ -Bis(3-(tert-butoxycarbonylamino)propyl)-4,4ꢀ -azo-
benzenedicarboxamide (0.19 g, 0.33 mmol) was dissolved in
4 mol dm−3 HCl in dioxane (8 cm3) and the solution was stirred for
2h at room temperature. The resultantprecipitate was separated by
filtration and redissolved in saturated aqueous sodium hydroxide
(75 cm3). That solution was extracted with EtOAc (3 × 50 cm3)
and the combined extracts were dried (MgSO4), and concentrated
under reduced pressure to afford the title compound 11 as an
orange powder (0.12 g, 95%); mp 280–282 ◦C (dec.); dH (300 MHz,
DMSO-d6) 8.97 (2H, t, J 5.5), 8.11 (4H, d, J 8.5), 7.99 (4H, d, J
8.5), 3.38–3.35 (8H, m), 2.88–2.81 (4H, m), 1.90–1.82 (4H, m);
dC (75.5 MHz, DMSO-d6) 165.6, 153.3, 136.8, 128.6, 122.6, 36.8,
36.4, 27.3; m/z (ESI, positive) 383 [(M + H+) 100], 405 [(M +
Na+), 15]; elemental analysis: found: C, 52.36; H, 6.28; N, 18.22.
C20H26N6O2·2HCl requires C, 52.75; H, 6.20; N, 18.45%.
[(E)-N,Nꢀ-Bis(4-chloro-6-methoxy-1,3,5-triazin-2-yl)-4,4ꢀ-
azobenzenedicarboxamide]-[a-cyclodextrin]-[2]-[rotaxane] (14b)
A mixture of a-CD (3.0 g, 3.1 mmol) and the azobenzene 12
(100 mg, 0.47 mmol) in water (25 cm3) adjusted to pH 10 with
triethylamine was stirred at room temperature for 2 h, before the
triazine 13 (0.34 g, 1.9 mmol) was added and that mixture was
stirred at room temperature for an additional 12 h. The resulting
solution was washed with EtOAc (5 × 25 cm3) and concentrated
under reduced pressure.
The residue dissolved in water (40 cm3) and the solution
was applied to a Diaion HP-20 column (310 × 25 mm). The
column was eluted with a water–methanol solvent gradient and
fractions eluting with 20–30% aqueous methanol were combined
and concentrated under reduced pressure. HPLC of the residue
gave the title compound 14b as an orange powder (128 mg, 19%);
mp 262–265 ◦C (dec.); dH (500 MHz, MeOH-d4) 8.46 (2H, d, J
8.5), 8.09 (2H, d, J 8.5), 7.96 (2H, d, J 8.5), 7.80 (2H, d, J 8.5),
4.92 (6H, d, J 3.5), 4.13 (3H, s), 4.10 (3H, s), 3.85–3.70 (18H,
m), 3.60–3.45 (18H, m); dC (75.5 MHz, MeOH-d4) 166.4, 166.2,
149.6, 149.1, 142.2, 126.6, 124.2, 121.7, 103.5, 82.7, 74.9, 73.4,
73.3, 73.2, 72.9, 61.2; m/z (ESI, positive) 1493 (M + Na+); TLC
(5 : 4 : 3 v/v/v, n-BuOH–EtOH–H2O) Rf 0.50 (relative to the
solvent front), 4.0 (relative to a-CD); HPLC: tR 21.0 min [Luna
Phenomenex column (250 × 10 mm), eluting with H2O–MeCN
(9 : 1, v/v), flow rate 3.0 cm3 min−1]; elemental analysis: found: C,
41.75; H, 5.82; N, 8.70. C56H76Cl2N10O32.7H2O requires C, 42.08;
H, 5.68; N, 8.76%.
[(E)-N,Nꢀ-Bis(4-phenylamino-6-methoxy-1,3,5-triazin-2-yl)-
4,4ꢀ-diaminostilbene]-[a-cyclodextrin]-[2]-[rotaxane] (16a)
A solution of the [2]-rotaxane 14a (30 mg, 20 lmol) in 50% aqueous
acetonitrile (10 cm3) was adjusted to pH 9 with triethylamine,
before aniline (19 mg, 20 lmol) was added and the mixture was
stirred at 50 ◦C for 3 h. HPLC of the crude product obtained
by concentration of the reaction mixture under reduced pressure
gave the title compound 16a as a colourless powder (11 mg, 33%);
dH (500 MHz; DMSO-d6) 9.81 (1H, s), 9.71 (1H, s), 9.47 (2H, s),
7.83 (4H, d, J 7.5), 7.80–7.75 (6H, m), 7.31 (4H, t, J 7.5), 7.16
(2H, m), 7.00 (2H, t, J 7.5), 6.88 (2H, m), 5.44 (6H, s), 5.31 (6H,
s), 4.77 (6H, d, J 3.0), 4.45 (6H, t, J 5.0), 3.94 (6H, s), 3.70–3.73
[(E)-N,Nꢀ-Bis(4-chloro-6-methoxy-1,3,5-triazin-2-yl)-
4,4ꢀ-diaminostilbene]-[a-cyclodextrin]-[2]-[rotaxane] (14a)
A mixture of a-CD (0.69 g, 0.71 mmol) and the stilbene 1 (50 mg,
0.24 mmol) in water (80 cm3) adjusted to pH 9 with triethylamine
was stirred at room temperature for 2 h, before the triazine 13
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(12H, m), 3.61 (6H, m), 3.47 (6H, apparent t, J 4.0), 3.32 (6H, m),
3.26 (6H, m); dC (500 MHz, DMSO-d6) 170.8, 164.9, 128.5, 125.7,
120.1, 102.1, 81.6, 73.2, 72.2, 71.8, 59.2, 54.0; m/z (ESI, positive)
1583.578 (M + H+) (calculated for C70H90N10O32 m/z 1583.580);
TLC (5 : 4 : 3 v/v/v, n-BuOH–EtOH–H2O) Rf 0.75 (relative to the
solvent front), 2.1 (relative to a-CD); HPLC tR 18.9 min [YMC-
PACK ODS-AQ column (250 × 20 mm), eluting with H2O–MeCN
(3 : 1, v/v), flow rate 10.0 cm3 min−1]; elemental analysis: found:
C, 46.74; H, 6.45; N, 7.52. C70H90N10O32·12H2O requires C, 46.72;
H, 6.38; N, 7.78%.
[(Z)-N,Nꢀ-Bis(3-(4,6-dimethoxy-1,3,5-triazin-2-ylamino)propyl)-
4,4ꢀ-azobenzenedicarboxamide]-[a-cyclodextrin]-[2]-[rotaxane] (19)
A solution of the trans-azobenzene-based rotaxane 9a (30 mg, 18
lmol) in water (0.6 dm3) in a quartz reaction vessel was irradiated
at 350 nm in a Luzchem photochemical reactor for 0.25 h, before
it was concentrated under reduced pressure to a volume of 3 cm3.
HPLC of this solution afforded a 65 : 35 mixture of the title
compound 19 and the trans-isomer 9a as an orange powder (12 mg,
40%). The title compound 19 showed: dH (500 MHz, MeOH-d4)
7.83 (2H, d, J 8.5), 7.75 (2H, d, J 8.5), 6.95 (4H, d, J 8.5), 2.08–
2.07 (2H, m), 1.89–1.87 (2H, m); HPLC tR 3.74 min [YMC-PACK
ODS-AQ column (250 × 10 mm), eluting with H2O–MeCN (3 : 1,
v/v), flow rate 3.0 cm3 min−1].
[(E)-N,Nꢀ-Bis(4-(3-aminopropylamino)-6-methoxy-1,3,5-triazin-
2-yl)-4,4ꢀ-azobenzenedicarboxamide]-[a-cyclodextrin]-[2]-
[rotaxane] (16b)
To a solution of the [2]-rotaxane 14b (25 mg, 17 lmol) in anhydrous
DMF (1 cm3), 1,3-diaminopropane (2.8 lm3, 40 lmol) was added,
and the mixture was left stirring for 10 h at room temperature,
before it was added dropwise to acetone (10 cm3). The resultant
precipitate was collected by centrifugation and resuspended in
acetone (15 cm3). The solid was collected, again by centrifugation.
HPLC of this material gave the title compound 16b as an orange
powder (20 mg, 76%); mp 282–285 ◦C (dec.); dH (500 MHz,
MeOH-d4) 8.47 (2H, d, J 8.5), 8.03 (2H, d, J 8.5), 7.94 (2H,
d, J 8.5), 7.85 (2H, d, J 8.5), 4.90 (6H, d, J 3.5), 4.13 (3H, s), 4.10
(3H, s), 3.81–3.73 (18H, m), 3.55–3.49 (26H, m), 2.07–2.00 (4H,
m); dC (75.5 MHz, MeOH-d4) 166.4, 166.2, 126.6, 124.4, 121.9,
121.5, 117.2, 103.9, 83.2, 75.0, 75.9, 73.3, 73.2, 72.9, 61.2, 37.0,
36.0, 28.7; m/z (ESI, positive) 1548 (M + H+); TLC (5 : 4 : 3 :
2 v/v/v/v, i-PrOH–EtOH–H2O–AcOH) Rf 0.45 (relative to the
solvent front), 0.56 (relative to the [2]-rotaxane 14b); HPLC tR
5.2 min [Luna Phenomenex column (250 × 10 mm), eluting with
H2O–MeCN–TFA (85 : 15 : 0.1, v/v/v), flow rate 3.0 cm3 min−1].
Acknowledgements
The authors acknowledge support received for this work from the
Australian Research Council.
Notes and references
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