Efficient synthesis of a hetero[4]rotaxane by a threading-stoppering- followed-by-clipping approach

Article abstract of DOI:10.1039/c001343a

A "threading-stoppering-followed-by-clipping" approach was used for the synthesis of a hetero[4]rotaxane, in which one cucurbit[6]uril (CB[6]) and two hetero crown ether macrocycles are threaded onto one dumbbell-shaped molecule. The process involves three steps: (1) threading of a CB[6] macrocycle onto a thread containing two dialkylammonium sites to form a CB[6]-based pseudo[2]rotaxane; (2) stoppering of the as-formed pseudo[2]rotaxane by imine condensation reaction followed by reduction/protonation to afford a CB[6]-based [2]rotaxane with two new dialkylammonium sites; and (3) selective clipping of two hetero crown ether macrocycles onto the newly-formed ammonium sites and subsequent reduction of the imine bonds in each crown ether to afford the final hetero[4]rotaxane in good yield. The whole process was followed by NMR spectroscopy and the structure of the hetero[4]rotaxane was confirmed by NMR spectroscopy, elemental analysis and mass spectrometry. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/c001343a

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Efficient synthesis of a hetero[4]rotaxane by a
“threading-stoppering-followed-by-clipping” approach†
Jun Yin, Chunyan Chi and Jishan Wu*
Received 21st January 2010, Accepted 23rd March 2010
First published as an Advance Article on the web 8th April 2010
DOI: 10.1039/c001343a
A “threading-stoppering-followed-by-clipping” approach was used for the synthesis of a
hetero[4]rotaxane, in which one cucurbit[6]uril (CB[6]) and two hetero crown ether macrocycles are
threaded onto one dumbbell-shaped molecule. The process involves three steps: (1) threading of a CB[6]
macrocycle onto a thread containing two dialkylammonium sites to form a CB[6]-based
pseudo[2]rotaxane; (2) stoppering of the as-formed pseudo[2]rotaxane by imine condensation reaction
followed by reduction/protonation to afford a CB[6]-based [2]rotaxane with two new
dialkylammonium sites; and (3) selective clipping of two hetero crown ether macrocycles onto the
newly-formed ammonium sites and subsequent reduction of the imine bonds in each crown ether to
afford the final hetero[4]rotaxane in good yield. The whole process was followed by NMR spectroscopy
and the structure of the hetero[4]rotaxane was confirmed by NMR spectroscopy, elemental analysis and
mass spectrometry.
and appropriate self-sorting binding process.18 Although the
Introduction
general synthetic methods such as “threading”, “stoppering” and
“clipping” for the homogenous rotaxanes can be applied to the
synthesis of heterorotaxanes, it is still not an easy task to assemble
multiple components into a well-defined complex. It becomes
even more challenging when two or more very similar binding
sites are involved in the self-sorting binding process. Due to
the synthetic challenges, only few examples of heterorotaxanes
have been reported. For example, Schalley et al. described the
synthesis a hetero[3]rotaxane by self-sorting threading of different
crown ethers onto a thread with different dialkylammonium
binding sites followed by stoppering.17 Anderson et al. reported
a hetero[3]rotaxane with two different p-systems clasped in a g-
cyclodextrin macrocycle.19 Li et al. also reported the synthesis
of hetero[3]rotaxanes with two different macrocycles by a “clip-
ping” approach.20 Recently, pseudo-heterorotaxanes based on self-
assorting threading of cucurbit[6]uril and cucurbit[7]uril were also
reported.21 However, the difficulties of synthesis and separation
still restricted the development of heterorotaxanes. Herein we
report an efficient synthesis of a hetero[4]rotaxane in which two
different macrocycles are selectively encircled onto two different
but similar binding sites by a new “threading-stoppering-followed-
by-clipping” approach.
Since the earliest synthesis of rotaxanes was reported in 1967,1
there have been a large number of rotaxane molecules prepared by
diversified strategies such as threading-followed-by-stoppering,2
slipping,3 and clipping4 due to their potential applications in
molecular electronic devices,5 nanoactuators,6 macroscopic liquid
transport,7 mesoporous silica-mounted nanovalves8 and con-
trolled drug release.9 Therefore rotaxanes have been of steadily
increasing attention in recent decades.10 Recently, some new
synthetic strategies were reported for the synthesis of mechanically
interlocked rotaxanes. For example, Leigh et al. described an
efficient approach to prepare rotaxanes in which a transition
metal ion in the cavity of a macrocycle can template and catalyze
the formation of rotaxanes.11 They also reported the synthesis
of a series of homogeneous rotaxanes by iterative addition of
multiple rings onto a single binding site.12 In addition, other
methods such as threading-followed-by-shrinking,13 threading-
followed-by-swelling14 and others15 have been used to synthesize
rotaxanes. Until today, most of the above methods were limited
to the synthesis of homorotaxanes which are composed of same
macrocycles and binding sites.16 In contrast, heterorotaxanes
possess a structural character in which the macrocycles and
the binding sites on the dumbbell-like thread have different
chemical composition, and they could exhibit multifunctional
character owing to the existence of different components.17 Thus,
heterorotaxanes could be a complementary structure of the
normal homogeneous rotaxanes. The synthesis of heterorotaxanes
is more challenging due to their structural complexity, that
is, different components must be selectively located at specific
binding sites, and this requires a careful design of templates
Results and discussion
Design of synthetic strategy
As mentioned above, the synthesis of a hetero[n]rotaxane requires
multiple templates and self-sorting binding. Herein, in our target
hetero[4]rotaxane molecule, a dumbbell-shaped thread containing
two types of dialkylammonium binding sites is selectively encircled
by two hetero crown ether macrocycles and one cucurbit[6]uril
(CB[6]) ring as depicted in Scheme 1. Such a design is based on
two facts: (1) the CB[6] has high affinity with the alkylammonium
salts to form pseudorotaxanes,22 and our recent work showed
Department of Chemistry, National University of Singapore, 3 Science Drive
3, Singapore 117543. E-mail: chmwuj@nus.edu.sg; Fax: (+65) 6779-1691
† Electronic supplementary information (ESI) available: NMR and mass
spectra. See DOI: 10.1039/c001343a
2594 | Org. Biomol. Chem., 2010, 8, 2594–2599
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Scheme 1 The schematic representation of the “threading-stoppering-followed-by-clipping” approach for the synthesis of a hetero[4]rotaxane.
Scheme 2 Regents and conditions: (a) (i) LiAlH4, THF; (ii) PCC, DCM, 33%; (b) TFA, DCM, quantitative; (c) (i) CB[6], H2O, reflux; (ii)
NH4PF6 (aq), 87%; (d) (i) 3,5-dimethoxybenzylamine, toluene; (ii) NaBH4, THF–MeOH, 96%; (e) (i) TFA, DCM, (ii) NH4PF6 (aq), 85%; (f) (i)
2,6-pyridinedicarboxaldehyde, tetraethyleneglycol bis(2-aminophenyl)ether, CH3CN; (ii) BH3·THF, 94%.
that pure CB-based pseudo[n]rotaxanes (n = 2, 3, 4, 5) could be
separated from their acid aqueous solutions by a simple threading-
followed-by-precipitation method;23 (2) a series of homogeneous
[n]rotaxanes have been prepared by clipping of the subunits of
a wheel-like component onto the dibenzylammonium sites on a
dumbbell-like thread molecule.4 In the first step, a CB[6] ring is
threaded onto a thread containing two dialkylammonium sites
together with two terminal functional groups. This is followed
by stoppering reactions by attaching two bulky stoppers to form
a [2]rotaxane. In this stage, it is necessary to ensure that no
dethreading of CB[6] takes place and two new binding sites (herein,
dibenzylammonium) should also be generated by functional group
transformation. Finally, a clipping reaction will be conducted
to form two new macrocycles surrounding the newly generated
dialkylammonium sites.
Synthesis and characterizations of the hetero[4]rotaxane 9
Scheme 2 outlines the detailed synthetic route of a key intermediate
ammonium salt 3 containing two terminal aldehyde groups. The
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 2594–2599 | 2595
©

View Article Online
starting material 1 was first synthesized according to literature.24
The symmetrical diester 1 with two Boc-protected dialkyl diamines
was reduced by LiAlH4 in dry THF and the obtained alcohol was
subsequently oxidized in dry DCM by pyridinium chlorochromate
(PCC) to give the dialdehyde 2 in 33% yields for two steps. Removal
of the Boc groups and simultaneous protonation of 2 by treatment
with trifluoroacetic acid (TFA) in DCM afforded the ammonium
salt 3 in a quantitative yield. The key intermediate compound 3
was then submitted for a threading process with CB[6] to form
a pseudo[2]rotaxane and we found that the choice of solvent
was very important in such a threading process. Threading of
CB[6] onto 3 was conducted in different solvents and followed by
1H NMR spectroscopy. It was found that there was no effective
threading in CF3CO2D/D2O (1 : 1, v/v), a good solvent system
to dissolve both compounds (see Figure S1 ESI†). Such weak
binding is due to the high affinity of CB[6] with the protons in
solvent.22 In the 0.2 M NaCl in D2O, when one equivalent CB[6]
was added, the resonances for the aldehyde protons and aromatic
protons of 3 were split into two sets of peaks, with one set showing
an upfield shift whereas the second set displaying almost no shift
(Figure S2 ESI†), indicating that one of the benzaldehyde units
was encircled by CB[6] to form a pseudo[2]rotaxane 4. Addition
of excessive CB[6] led to a dynamic mixture of pseudo[2]rotaxane
and pseudo[3]rotaxane 5 (Scheme 3), but it was clear that no
CB[6] ring was threaded onto the central hexyl chain because
there is no obvious shift of the resonances for the hexyl after
threading. This also suggests that one portal of the CB[6] binds
with the dialkyl ammonium site while the second portal strong
binds with Na+ in water.22 When the threading was performed
in pure water under reflux for 24 h under nitrogen atmosphere,
the CB[6] was successfully threaded onto the central hexyl chain
(Scheme 3) to form a pseudo[2]rotaxane 6 due to the strong binding
between the two dialkyl ammonium sites and CB[6].22 After
cooling, the excessive insoluble CB[6] was removed by filtration
and the filtrate was treated with saturated NH4PF6 solution to
give the 6 as white precipitate in nearly quantitative yield after
this counter-ion exchange process.23 The resonances of central
methylene protons were shifted upfield to d = 0.45–0.70 ppm due
to the shielding effect of CB[6] on the hexyl chain. In addition, the
resonance at 5.76 ppm correlated to the endo-H of the methylene
bridges in the CB[6] was split into multiple peaks due to the
binding of ammonium site with CB[6]. Electrospray ionization
mass spectrometry (ESI-MS) further confirmed the formation of
a pseudo[2]rotaxane 6 (see ESI†).
the reduction, the ammonium sites close to the CB[6] ring were
also neutralized and re-protonation of the free amine with excess of
TFA and subsequent counter-ion exchange with NH4PF6 afforded
the [2]rotaxane 8 in 85% yield for two steps. Most importantly, the
CB[6] did not slip out from the thread during the condensation and
reduction processes and two new dibenzylammonium sites were
generated which are ready for the subsequent clipping reaction.
The structure of the [2]rotaxane 8 was confirmed by both NMR
(Fig. 1A) and ESI mass spectrometry (see ESI†). The clipping re-
action to form a dynamic hetero[4]rotaxane was then conducted in
CD3CN by mixing the [2]rotaxane 8 together with two equivalents
each of tetra(ethylene glycol) bis(2-aminophenyl)ether and 2,6-
1
pyridinedicarboxaldehyde,4 and the reaction was followed by H
NMR spectroscopy. Upon clipping reaction, the resonances of the
stopper units (-CH3 and -Ph) protons were shifted upfield, indicat-
ing that the clipping reaction took place at the dibenzylammonium
sites. A characteristic resonance peak at 8.72 ppm assigned to
imine protons was observed (Fig. 1B). The as-formed rotaxane
was not separated due to the dynamic character of the imine
∑
bond and it was submitted to subsequent reduction by BH3 THF
to afford the kinetically stable hetero[4]rotaxane 9 in 94% yield
for two steps after repeated washing the solid by chloroform
and methanol. Compared with the dynamic hetero[4]rotaxane,
+
the resonance for the ammonium protons (-NH2 -) close to the
stopper also showed an upfield shift.4 Moreover, the two sets
of resonance peaks of stopper units (-Ph) displayed crossed
upfield and downfield shift. Through the 2D NOESY NMR
experiment, we identified some obvious signals for the correlations
between macrocycle components (CB[6] and crown ether) and
the dumbbell-shaped component in the hetero[4]rotaxane 9. For
example, the benzene rings of the dumbbell-shaped component
were strongly shielded by the hetero crown ether components
and obvious correlations were observed between the crown ethers
and the central benzene ring (Hf, He) and the neighboring–CH2-
+
NH2 -CH2- (Hd, He) sites. Similarly, correlation of the resonaces
for CB[6] with the central hexyl unit was observed (see Figure
S4–S6 ESI†). The structures of the final hetero[4]rotaxane 9 was
also confirmed by ESI mass spectrometry and elemental analysis.
Three peaks at m/z = 657.02 for [M+H2O-4PF6 ]4+, 875.81 for
-
[M+H2O-3PF6 -HPF6]3+ and 924.40 for [M+H2O-3PF6 ]3+ with
-
-
Scheme 3 The schematic representation of the threading process of CB[6]
with compound 3 in different solvents.
Subsequently, condensation of the as-formed pseudo-
[2]rotaxane 6 with 3,5-dimethoxybenzylamine gave the respective
imine [2]rotaxane in a high yield, which was reduced by NaBH4 to
give the kinetically stable amine [2]rotaxane 7 in 98% yield. During
Fig. 1 Partial 1H NMR spectra (300 MHz, CD3CN, 298 K) of 8 (A);
clipping reaction mixture (dynamic rotaxane) (B) and 9 (C) (the protons
are labelled in Scheme 1).
2596 | Org. Biomol. Chem., 2010, 8, 2594–2599
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
well resolved isotope distribution were observed for 9 in CH3CN
(see Supporting Information).25 The obtained heterorotaxane is
also kinetically stable and no obvious change of their NMR
spectra recorded in DMSO-d6 at different temperatures was
observed (Figure S3 ESI†).
by column chromatography (silica gel, EtOAc–hexane = 1/3 to
1/1, v/v) to give the title product 2 as a yellow oil in 33% yield.
Compound 2 is unstable and thus it was used immediately for next
deprotection step of. To a solution of 2 (0.11 g, 0.2 mmol) in dry
DCM (20 mL), trifluoroacetic acid (0.3 mL, 4.0 mmol) was added
and the mixture was stirred for 15 h at room temperature under
nitrogen atmosphere. The solvent was removed under vacuum to
give the 3. Compound 2: 1H NMR (300 MHz, CDCl3): d ppm =
9.99 (s, 2H, CHO), 7.83 (d, J = 8.1 Hz, 4H, Ar), 7.36 (br, 4H, Ar),
4.47 (br, 4H, CH2), 3.16 (br, 4H, CH2), 1.40–1.53 (m, 22H, Boc
and CH2), 1.23–1.25 (m, 4H, CH2). Compound 3, m.p. 187.5 ◦C
Conclusions
In conclusion, a “threading-stoppering-followed-by-clipping” ap-
proach was used for the efficient synthesis of a hetero[4]rotaxane
9. Compound 9 represents as a new member of heterorotaxane
family which are usually not easy to synthesize. In principle, this
method can also be used for the synthesis of more complicated
and higher order heterorotaxanes if the threading, stoppering and
clipping processes do not interfere with each other. In particular,
we are interested in the synthesis of functional heterorotaxanes
in which different components with specific functionalities are
introduced in one mechanically interlocked structure by a similar
synthetic strategy in the future.
1
(decomp.): H NMR (300 MHz, CF3CO2D/D2O = 1 : 1, v/v): d
ppm = 9.93 (br, 2H, CHO), 8.00 (br, 4H, Ar), 7.66 (br, 4H, Ar),
4.27–4.45 (m, 4H, CH2), 3.03–3.19 (m, 4H, CH2), 1.77 (br, 4H,
CH2), 1.38 (br, 4H, CH2). 13C NMR (75 MHz, CF3CO2D/D2O):
d ppm = 199.20, 135.35, 134.74, 134.69, 134.34, 54.79, 51.20,
29.22, 27.47. ESI MS: m/z = 375.21 ([M–2 CF3COOH + Na+]),
calculated exact mass: 375.20. Anal. Calcd for C22H30F12N2O2P2:
C, 41.00; H, 4.69; N, 4.35. Found: C, 40.87; H, 4.82; N, 4.20.
Synthesis of pseudo[2]rotaxane 6. To a solution of the 3 in H2O,
cucurbit[6]uril (0.24 g, 0.24 mmol) was added and the mixture was
refluxed for 24 h under nitrogen atmosphere. After cooling, the
mixture was filtered and the filtrate was treated with saturated
NH4PF6 (2 mL, aq) to yield a white precipitate. The solid was
collected by filtration, washed with water and dried under vacuum
to give the title compound 6 in 87% yield. Compound 6, m.p.
Experimental
Materials and methods
All reagents and starting materials were obtained from commercial
suppliers and used without further purification. Column chro-
matography was performed on silica gel 60 (Merck 40–60 nm, 230–
400 mesh). Deuterated solvents (Cambridge Isotope Laboratories)
for NMR spectroscopic analyses were used as received. All NMR
spectra were recorded on Bruker AMX500 at 500 MHz and Bruker
ACF300 at 300 MHz spectrometers. All chemical shifts are quoted
in ppm, relative to tetramethylsilane, using the residual solvent
peak as a reference standard. The 2D NOESY spectra of 9 were
recorded on Bruker AMX500 at 500 MHz over a spectral width of
5122 Hz with a mixing time 500 ms and a relaxation time of 2.5 s.
Melting points were determined on a Buchi Melting point B-450
apparatus and were uncorrected. Elemental analyses (C, H, N)
were performed on a Vario EL Elementar (Elementar Analyzen-
systeme, Hanau, Germany). Mass spectra were recorded on a
Finnigan MAT LCQ with ESI ionization and Bruker Autoflex
MALDI-TOF instrument using 1,8,9-trihydroxyanthracene as a
matrix.
◦
1
218.4 C (decomp.): H NMR (300 MHz, CD3CN): d ppm =
10.06 (s, 2H, CHO), 7.91–8.01 (m, 8H, Ar), 5.76 (m, 12H, CB),
5.36 (br, 12H, CB), 4.44 (br, 4H, CH2), 4.16 (m, 12H, CB), 2.93
(br, 4H, CH2), 0.40–0.64 (br, 8H, CH2). ESI MS: m/z = 684.24
-
([M + H2O - 2PF6 ]), calculated exact mass: 684.27. Anal. Calcd
for C58H68F12N26O15P2: C, 41.98; H, 4.13; N, 21.95. Found: C,
41.82; H, 4.32; N, 21.87.
Synthesis of [2]rotaxane 7. A mixture of 6 (328 mg, 0.2 mmol)
and 3,5-dimethoxybenzylamine (67 mg, 0.4 mmol) in dry MeCN
(10 mL) and CHCl3 (10 mL) was stirred for 2 h at room
temperature. The solvents were removed under vacuum, and
toluene (10 mL) was added. The mixture was stirred at room
temperature for 2 h and the toluene was removed at 60 ◦C on
a rotary evaporator. Additional toluene was added and removed
again. Such process was repeated for 3 times, so that the trace
amount of water was removed from the reaction system and the
imine was obtained in quantitative yield. To a solution of imine
(387 mg, 0.20 mmol) in dry THF (15 mL) and MeOH (15 mL),
NaBH4 (151 mg, 4.0 mmol) was added in small portion. After
stirring for 24 h at room temperature, the solvents were removed
under vacuum, and the residue was collected by filtration and
washed with water and CHCl3, and dried under vacuum to give
the title product 7 in 98% yield. Compound imine: 1H NMR
Synthesis of the dialdehyde 2 and ammonium 3. A suspension of
LiAlH4 (0.15 g, 4.0 mmol) in anhydrous THF (20 mL) was slowly
added via a dropping funnel to a solution of compound 1 (0.61 g,
1.0 mmol) in anhydrous THF (10 mL) at 0 ◦C, and the resulting
suspension was stirred under nitrogen atmosphere for 24 h. The
reaction mixture was subsequently quenched by slowly adding the
ground powder of Na2SO4·10H2O and Celite (1 : 1, w/w). After
stirring for 30 min, the mixture was filtered and the excess of
solvent in the filtrate was removed under vacuum to give the diol.
The solution of the obtained diol in dry DCM (10 mL) was added
dropwise to a suspension of pyridinium chlorochromate (PCC)
(0.65 g, 3.0 mmol) in dry DCM (30 mL) at 0 ◦C. The mixture was
allowed to warm up to room temperature and stirred for overnight
under nitrogen atmosphere. The reaction was quenched by adding
1 M NaOH (10 mL) and the organic phase was washed with
H2O (200 mL). The organic layer was dried over Na2SO4 and the
solvent was removed under vacuum and the residue was purified
=
(300 MHz, CD3CN): d ppm = 8.49 (s, 2H, CH N), 7.77–7.98
(m, 8H, Ar), 6.53 (br, 4H, Ar), 6.4 (br, 2H, Ar), 5.76 (m, 12H,
CB), 5.35 (br, 12H, CB), 4.72 (s, 4H, CH2), 4.36 (br, 4H, CH2),
4.16 (m, 12H, CB), 3.76 (br, 12H, CH3), 2.92 (br, 4H, CH2), 0.38–
◦
1
0.62 (br, 8H, CH2). Compound 7, m.p. > 300.0 C: H NMR
(300 MHz, DMSO): d ppm = 7.61–7.66 (m, 4H, Ar), 7.41–7.44
(m, 4H, Ar), 6.53 (br, 4H, Ar), 6.35 (br, 2H, Ar), 5.61 (m, 12H,
CB), 5.49 (br, 12H, CB), 4.37 (m, 12H, CB), 4.28 (br, 4H, CH2),
3.73 (br, 12H, CH3), 3.72 (br, 4H, CH2), 3.64 (br, 4H, CH2), 2.81
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 2594–2599 | 2597
©

View Article Online
(br, 4H, CH2), 0.34–0.85 (br, 8H, CH2). ESI MS: m/z = 835.35
([M + H2O + 2H+]), 556.23 ([M + H2O + 3H+]); calculated exact
mass: 835.38, 556.58. MALDI-TOF MS: m/z = 1688.681 ([M +
H2O + H+]). Anal. Calcd for C76H92F12N28O17: C, 54.67; H, 5.55;
N, 23.49. Found: C, 54.80; H, 5.41; N, 23.33.
2000, 6, 2274–2287; (f) D. W. Zehnder and D. B. Smithrud, Org. Lett.,
2001, 3, 2485–2487; (g) N. Watanabe, T. Yagi, N. Kihara and T. Takata,
Chem. Commun., 2002, 2720–2721; (h) W.-C. Hung, K.-S. Liao, Y.-H.
Liu, S.-M. Peng and S.-H. Chiu, Org. Lett., 2004, 6, 4183–4186.
3 (a) M. Handel, M. Plevoets, S. Gestermann and F. Vogtle, Angew.
Chem., 1997, 109, 1248–1250, (Angew. Chem., Int. Ed. Engl., 1997, 36,
1199–1201); (b) P. R. Ashton, I. Baxter, M. C. T. Fyfe, F. M. Raymo,
N. Spencer, J. F. Stoddart, A. J. P. White and D. J. Williams, J. Am.
Chem. Soc., 1998, 120, 2297–2307; (c) S. J. Cantrill, J. A. Preece, J. F.
Stoddart, Z.-H. Wang, A. J. P. White and D. J. Williams, Tetrahedron,
2000, 56, 6675–6681.
4 (a) P. T. Glink, A. I. Oliva, J. F. Stoddart, A. J. P. White and D. J.
Williams, Angew. Chem., 2001, 113, 1922–1927, (Angew. Chem., Int.
Ed., 2001, 40, 1870–1875); (b) M. Asakawa, G. Brancato, M. Fanti,
D. A. Leigh, T. Shimizu, A. M. Z. Slawin, J. K. Y. Wong, F. Zerbetto
and S. Zhang, J. Am. Chem. Soc., 2002, 124, 2939–2950; (c) J. A. Wisner,
P. D. Beer, M. G. B. Drew and M. R. Sambrook, J. Am. Chem. Soc.,
2002, 124, 12469–12476; (d) J. Wu, K. C.-F. Leung and J. F. Stoddart,
Proc. Natl. Acad. Sci. U. S. A., 2007, 104, 17266–17271.
5 (a) Molecular Electronics: Science and Technology (ed.: A. Aviram,
M. Ratner), New York Academy of Sciences, New York, 1998; (b) C. P.
Collier, G. Mattersteig, E. W. Wong, Y. Luo, K. Beverly, J. Sampaio,
F. M. Raymo, J. F. Stoddart and J. R. Heath, Science, 2000, 289, 1172–
1175; (c) H. Yu, Y. Luo, K. Beverly, J. F. Stoddart, H.-R. Tseng and J. R.
Heath, Angew. Chem., 2003, 115, 5884–5889, (Angew. Chem., Int. Ed.,
2003, 42, 5706–5711); (d) J. W. Choi, A. H. Flood, D. W. Steuerman,
S. Nygaard, A. B. Braunschweig, N. N. P. Moonen, B. W. Laursen, Y.
Luo, E. DeIonno, A. J. Peters, J. O. Jeppesen, K. Xu, J. F. Stoddart and
J. R. Heath, Chem.–Eur. J., 2006, 12, 261–279; (e) J. E. Green, J. W.
Choi, A. Boukai, Y. Bunimovich, E. Johnston-Halperin, E. Delonno,
Y. Luo, B. A. Sheriff, K. Xu, Y. S. Shin, H.-R. Tseng, J. F. Stoddart and
J. R. Heath, Nature, 2007, 445, 414–417.
6 (a) M. C. Jime´nez-Molero, C. Dietrich-Buchecker, J.-P. Sauvage and
A. De Cian, Angew. Chem., 2000, 112, 1351–1354, (Angew. Chem., Int.
Ed., 2000, 39, 1295–1298); (b) J.-P. Collin, C. Dietrich-Buchecker, P.
Gavin˜a, M. C. Jimenez-Molero and J.-P. Sauvage, Acc. Chem. Res.,
2001, 34, 477–487; (c) T. J. Huang, B. Brough, C.-M. Ho, Y. Liu, A. H.
Flood, P. A. Bonvallet, H.-R. Tseng, J. F. Stoddart, M. Baller and S.
Magonov, Appl. Phys. Lett., 2004, 85, 5391–5393; (d) Y. Liu, A. H.
Flood, P. A. Bonvallet, S. A. Vignon, B. H. Northrop, H.-R. Tseng,
J. O. Jeppesen, T. J. Huang, B. Brough, M. Baller, S. Magonov, S. D.
Solares, W. A. Goddard, C.-M. Ho and J. F. Stoddart, J. Am. Chem.
Soc., 2005, 127, 9745–9759; (e) J. Wu, K. C.-F. Leung, D. Ben´ıtez, J.-Y.
Han, S. J. Cantrill, L. Fang and J. F. Stoddart, Angew. Chem., 2008,
120, 7580–7584, (Angew. Chem., Int. Ed., 2008, 47, 7470–7474).
7 J. Berna´, D. A. Leigh, M. Lubomska, S. M. Mendoza, E. M. Pe´rez, P.
Rudolf, G. Teobaldi and F. Zerbetto, Nat. Mater., 2005, 4, 704–710.
8 (a) R. Hernandez, H.-R. Tseng, J. W. Wong, J. F. Stoddart and J. I.
Zink, J. Am. Chem. Soc., 2004, 126, 3370–3371; (b) T. D. Nguyen,
H.-R. Tseng, P. C. Celestre, A. H. Flood, Y. Liu, J. F. Stoddart and J. I.
Zink, Proc. Natl. Acad. Sci. U. S. A., 2005, 102, 10029–10034; (c) T. D.
Nguyen, Y. Liu, S. Saha, K. C. F. Leung, J. F. Stoddart and J. I. Zink,
J. Am. Chem. Soc., 2007, 129, 626–634.
¨
¨
Synthesis of [2]rotaxane 8. To a suspension of 7 (330 mg,
0.2 mmol) in dry DCM (20 mL), TFA (0.6 mL, 8.0 mmol) was
added at room temperature. After stirring for overnight under
nitrogen atmosphere, the solvent was removed under vacuum.
The residue was dissolved in MeOH (1 mL), and then saturated
NH4PF6 (2 mL, aq) was added to yield a white precipitate.
After filtering, washing with H2O and dry under vacuum, the
title compound 8 was obtained in 85% yield. compound 8, m.p.
241.0 ◦C: 1H NMR (300 MHz, CD3NO2): d ppm = 7.92 (m, 4H,
Ar), 7.63 (m, 4H, Ar), 6.64 (br, 4H, Ar), 6.57 (br, 2H, Ar), 5.86
(m, 12H, CB), 5.47 (br, 12H, CB), 4.53 (br, 4H, CH2), 4.52 (br,
4H, CH2), 4.40 (br, 4H, CH2), 4.30 (m, 12H, CB), 3.79 (br, 12H,
CH3), 3.00 (br, 4H, CH2), 0.49–0.85 (br, 8H, CH2). ESI MS: m/z =
-
835.34 ([M + H2O - 2HPF6 - 2PF6 ]), 556.23 ([M + H2O - HPF6
-
- 3PF6 ]), calculated exact mass: 835.37, 556.58. Anal. Calcd for
C76H96F24N28O17P4: C, 40.50; H, 4.29; N, 17.40. Found: C, 40.35;
H, 4.42; N, 17.27.
Synthesis of hetero[4]rotaxane 9. A mixture of 8 (89 mg,
0.04 mmol), 2,6-pyridinedicarboxaldehyde (11 mg, 0.08 mmol)
and tetraethyleneglycol bis(2-aminophenyl)ether (30 mg,
0.08 mmol) were stirred for 2 h in dry CH3NO2 under nitrogen
atmosphere. Then BH3·THF solution (0.3 mL) was added and the
mixture was further stirred overnight. The solvents were removed
under vacuum to yield a white precipitate. After washing with
DCM and MeOH, the title product 9 was obtained in 94% yield.
◦
1
Compound 9, m.p. 235.2 C: H NMR (500 MHz, CD3CN): d
+
ppm = 8.95 (br, 2H, NH2 ), 7.65–7.80 (br, 2H, Py), 7.34–7.38 (br,
8H, Ar), 6.99 (br, 4H, Ar), 6.71 (br, 12H, Ar), 6.43–6.47 (br, 4H,
Ar), 6.27 (br, 2H, Ar), 6.11 (br, 4H, Ar), 5.70 (m, 12H, CB), 5.34
(br, 12H, CB), 4.53 (br, 20H, CH2), 4.14 (m, 12H, CB), 3.73–4.10
(br, 32H, CH2), 3.41 (br, 12H, CH3), 2.80 (br, 4H, CH2), 0.33–0.56
-
(br, 8H, CH2). ESI MS: m/z = 924.41 ([M + H2O - 3PF6 ]);
-
-
875.82([M + H2O - HPF6 - 3PF6 ]); 657.02 ([M + H2O - 4PF6 ]),
calculated exact mass: 925.39, 876.74, 657.81. Anal. Calcd for
C130H162F24N34O27P4: C, 48.60; H, 5.08; N, 14.82. Found: C, 48.51;
H, 4.99; N, 15.01.
9 S. Saha, K. C. F. Leung, T. D. Nguyen, J. F. Stoddart and J. I. Zink,
Adv. Funct. Mater., 2007, 17, 685–693.
10 For selected reviews, see: (a) F. Vo¨gtle, Supramolecular Chemistry,
Wiley, New York, 1991; (b) D. J. Cram, J. M. Cram, Container
Molecules and Their Guests, Royal Society of Chemistry, Cambridge,
1994; (c) J.-M. Lehn, Supramolecular Chemistry, VCH, New York,
1995; (d) H. W. Gibson, in Large Ring Molecules (Ed.: J. A. Semlyen),
Wiley, New York, 1996; (e) Comprehensive Supramolecular Chemistry,
Vol. 6 (ed.: J. L. Atwood, J. E. D. Davies, D. D. MacNicol, F. Vo¨gtle),
Pergamon, Oxford, 1996; (f) Comprehensive Supramolecular Chemistry,
Vol. 9 (ed.: J.-P. Sauvage, M. W. Hosseini), Pergamon, Oxford, 1996;
(g) J. P. Sauvage, C. Dietrich-Buchecker, ed. Molecular Catenanes, Ro-
taxanes and Knots: A Journey through the World of MolecularTopology,
Wiley VCH: Weinheim, 1999; (h) V. Balzani, M. Venturi, A. Credi,
Molecular Devices and Machines: A Journey into the Nano World, Wiley
VCH: Weinheim, 2003; (i) T. Takata, N. Kihara and Y. Furusho, Adv.
Polym. Sci., 2004, 171, 1–75; (j) F. Huang and H. W. Gibson, Prog.
Polym. Sci., 2005, 30, 982–1018; (k) G. Wenz, B.-H. Han and A. Mu¨ller,
Chem. Rev., 2006, 106, 782–817; (l) J. A. Faiz, V. Heitz and J.-P. Sauvage,
Chem. Soc. Rev., 2009, 38, 422–442; (m) J. D. Crowley, S. M. Goldup,
A.-L. Lee, D. A. Leigh and R. T. McBurney, Chem. Soc. Rev., 2009, 38,
1530–1541; (n) K. M. Mu¨llen and P. D. Beer, Chem. Soc. Rev., 2009,
Acknowledgements
This work was financially supported by the AcRF Tier 1 FRC
grant (R-143-000-328-133) and the NUS Young Investigator
Award (R-143-000-356-101).
Notes and references
1 (a) I. T. Harrison and S. Harrison, J. Am. Chem. Soc., 1967, 89, 5723–
5724; (b) G. Schill and H. Zo¨llenkopf, Nachr. Chem. Techn., 1967, 79,
149.
2 (a) A. Harada, J. Li and M. Kamachi, Nature, 1992, 356, 325–
327; (b) C. G. Gong, Q. Ji, C. Subramaniam and H. W. Gibson,
Macromolecules, 1998, 31, 1814–1818; (c) J. Cao, M. C. T. Fyfe, J. F.
Stoddart, G. R. L. Cousins and P. T. Glink, J. Org. Chem., 2000, 65,
1937–1946; (d) Y. Tachibana, N. Kihara, Y. Ohga and T. Takata, Chem.
Lett., 2000, 806–807; (e) S. J. Cantrill, D. A. Fulton, A. M. Heiss, A. R.
Pease, J. F. Stoddart, A. J. P. White and D. J. Williams, Chem.–Eur. J.,
2598 | Org. Biomol. Chem., 2010, 8, 2594–2599
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
38, 1701–1713; (o) V. Balzani, A. Credi and M. Venturi, Chem. Soc.
Rev., 2009, 38, 1542–1550; (p) J. F. Stoddart, Chem. Soc. Rev., 2009, 38,
1802–1820.
18 (a) S. Liu, C. Ruspic, P. Mukhopadhyay, S. Chakrabarti, P. Y. Zavalij
and L. Isaacs, J. Am. Chem. Soc., 2005, 127, 15959–15967; (b) P.
Mukhopadhyay, A. Wu and L. Isaacs, J. Org. Chem., 2004, 69, 6157–
6164.
11 (a) V. Aucagne, K. D. Ha¨nni, D. A. Leigh, P. J. Lusby and D. B. Walker,
J. Am. Chem. Soc., 2006, 128, 2186–2187; (b) J. Berna´, J. D. Crowley,
S. M. Goldup, K. D. Ha¨nni, A.-L. Lee and D. A. Leigh, Angew. Chem.,
2007, 119, 5811–5815, (Angew. Chem., Int. Ed., 2007, 46, 5709–5713);
(c) V. Aucagne, J. Berna´, J. D. Crowley, S. M. Goldup, K. D. Ha¨nni,
D. A. Leigh, P. J. Lusby, V. E. Ronaldson, A. M. Z. Slawin, A. Viterisi
and D. B. Walker, J. Am. Chem. Soc., 2007, 129, 11950–11963; (d) J. D.
Crowley, K. D. Ha¨nni, A.-L. Lee and D. A. Leigh, J. Am. Chem. Soc.,
2007, 129, 12092–12093; (e) J. D. Crowley, D. A. Leigh, P. J. Lusby,
R. T. McBurney, L.-E. Perret-Aebi, C. Petzold, A. M. Z. Slawin and
M. D. Symes, J. Am. Chem. Soc., 2007, 129, 15085–15090; (f) J. Berna´,
S. M. Goldup, A.-L. Lee, D. A. Leigh, M. D. Symes, G. Teobaldi and
F. Zerbetto, Angew. Chem., 2008, 120, 4464–4468, (Angew. Chem., Int.
Ed., 2008, 47, 4392–4396); (g) M. J. Barrell, D. A. Leigh, P. J. Lusby
and A. M. Z. Slawin, Angew. Chem., 2008, 120, 8156–8159, (Angew.
Chem., Int. Ed., 2008, 47, 8036–8039).
19 E. J. F. Klotz, T. D. W. Claridge and H. L. Anderson, J. Am. Chem.
Soc., 2006, 128, 15374–15375.
20 (a) X. Zhao, X.-K. Jiang, M. Shi, Y.-H. Yu, W. Xia and Z.-T. Li, J. Org.
Chem., 2001, 66, 7035–7043; (b) L. Chen, X. Zhao, Y. Chen, C.-X.
Zhao, X.-K. Jiang and Z.-T. Li, J. Org. Chem., 2003, 68, 2704–2712.
21 (a) E. Masson, X. Lu, X. Ling and D. L. Patchell, Org. Lett., 2009, 11,
3798–3901; (b) G. Celtek, M. Artar, O. A. Scherman and D. Tuncel,
Chem.–Eur. J., 2009, 15, 10360–10363.
22 (a) J. W. Lee, S. Samal, N. Selvapalam, H.-J. Kim and K. Kim, Acc.
Chem. Res., 2003, 36, 621–630; (b) J. Lagona, P. Mukhopadhyay,
S. Chakrabarti and L. Isaacs, Angew. Chem., 2005, 117, 4922–4949,
(Angew. Chem., Int. Ed., 2005, 44, 4844–4870); (c) K. Kim, N.
Selvapalam, Y. H. Ko, K. M. Park, D. Kim and J. Kim, Chem. Soc.
Rev., 2007, 36, 267–279.
23 J. Yin, C. Chi and J. Wu, Chem.–Eur. J., 2009, 15, 6050–6057.
24 P. R. Ashton, V. Baldoni, V. Balzani, A. Credi, H. D. A. Hoffmann,
M.-V. Mart´ınez-D´ıaz, F. M. Raymo, J. F. Stoddart and M. Venturi,
Chem.–Eur. J., 2001, 7, 3482–3493.
25 The CB[6] containing pseudorotxanes and rotaxanes always contain
one or more strongly bounded H2O molecules in CH3CN as observed
by both MALDI-TOF and ESI mass spectrometry. This phenomenon
was also reported in single crystals of CB-based molecules, e.g., J. Kim,
I.-S. Jung, S.-Y. Kim, E. Lee, J.-K. Kang, S. Sakamoto, K. Yamaguchi
and K. Kim, J. Am. Chem. Soc., 2000, 122, 540–541. Collection of
13C NMR spectra of the CB-containing pseudorotaxane 6 and the
rotaxanes 7, 8 and 9 encountered problems due to their low solubility,
but their structure was clearly proved by 1H NMR spectra, elemental
analysis and HR ESI mass spectrometry..
12 A. M. Fuller, D. Leigh and P. L. Lusby, Angew. Chem., 2007, 119,
5103–5107, (Angew. Chem., Int. Ed., 2007, 46, 5015–5019).
13 I. Yoon, M. Narita, T. Shimizu and M. Asakawa, J. Am. Chem. Soc.,
2004, 126, 16740–16741.
14 C.-W. Chiu, C.-C. Lai and S.-H. Chiu, J. Am. Chem. Soc., 2007, 129,
3500–3501.
15 N. Kameta, K. Hiratani and Y. Nagawa, Chem. Commun., 2004, 466–
467.
16 H. W. Gibson, S. Liu, C. Gong, Q. Ji and E. Joseph, Macromolecules,
1997, 30, 3711–3727.
17 (a) W. Jiang, H. D. F. Winkler and C. A. Schalley, J. Am. Chem. Soc.,
2008, 130, 13852–13853; (b) W. Jiang and C. A. Schalley, Proc. Natl.
Acad. Sci. U. S. A., 2009, 106, 10425–10429.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 2594–2599 | 2599
©