Quantitative active transport in [2]rotaxane using a one-shot acylation reaction toward the linear molecular motor

Article abstract of DOI:10.1021/jo8013726

(Figure Presented) A rotaxane consisting of a crown ether wheel and a secondary ammonium salt axle, on which a neopentyl-type end-cap was placed close to the ammonium moiety, was prepared. When the rotaxane was treated by excess triethylamine, the wheel component thermodynamically moved over the proximate neopentyl group to deconstruct the interlocked structure. The wheel component in the rotaxane, however, quantitatively moved against the proximate end-cap by the action of trifluoroacetic anhydride in the presence of excess triethylamine. This motion, which was driven by the simple one-shot acylation reaction, can be referred as the active transport. When the distant end-cap is of the neopentyl-type, the axle can be thermally dethreaded from the distant end-cap after the acylative transport. The series of the wheel movement controlled by the neopentyl group can be the basic motion of the unidirectional linear molecular motor.

Full text of DOI:10.1021/jo8013726

Quantitative Active Transport in [2]Rotaxane Using a One-Shot
Acylation Reaction toward the Linear Molecular Motor
Yoshimasa Makita,*,† Nobuhiro Kihara,‡ and Toshikazu Takata*,§
Department of Chemistry, Osaka Dental UniVersity, 8-1 Kuzuhahanazono-cho, Hirakata,
Osaka, 573-1121, Japan, Department of Chemistry, Faculty of Science, Kanagawa UniVersity,
2946 Tsuchiya, Hiratsuka 259-1293, Japan, and Department of Organic and Polymeric Materials, Tokyo
Institute of Technology, Ookayama, Meguro-ku, Tokyo 152-8552 Japan
makita@cc.osaka-dent.ac.jp; ttakata@polymer.titech.ac.jp
ReceiVed July 4, 2008
A rotaxane consisting of a crown ether wheel and a secondary ammonium salt axle, on which a neopentyl-
type end-cap was placed close to the ammonium moiety, was prepared. When the rotaxane was treated
by excess triethylamine, the wheel component thermodynamically moved over the proximate neopentyl
group to deconstruct the interlocked structure. The wheel component in the rotaxane, however,
quantitatively moved against the proximate end-cap by the action of trifluoroacetic anhydride in the
presence of excess triethylamine. This motion, which was driven by the simple one-shot acylation reaction,
can be referred as the active transport. When the distant end-cap is of the neopentyl-type, the axle can
be thermally dethreaded from the distant end-cap after the acylative transport. The series of the wheel
movement controlled by the neopentyl group can be the basic motion of the unidirectional linear molecular
motor.
Introduction
can be changed by an external stimulus. It seems that an artificial
linear molecular motor can be constructed as an extension of
the stretching system.8 However, linear molecular motor and
stretching system are basically different because the track of
the natural linear molecular motor has polymeric structure. Since
the polymeric track in the linear molecular motor exhibits a
periodic potential surface (Figure 1), the forward and backward
sides of the motor are thermodynamically and kinetically
Since molecular motors,1 rotational motors such as ATPase,2
and linear motors such as the actin-myosin system3 and
kinesin-microtube system4 are essential components in living
systems, the construction of artificial molecular motors has
received considerable attention. Although various artificial
rotational molecular motors5 and stretching molecules6 have
been studied thus far, only limited research on artificial linear
molecular motors are reported.7
(5) (a) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007,
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In stretching molecular systems, the on-off mode is ther-
modynamically controlled: the mobile component migrates to
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* To whom correspondence should be addressed. (Y.M.) Tel: +81-72-864-
3162. Fax: +81-72-864-3162. (T.T.) Tel: +81-3-5734-2898. Fax: +81-3-5734-
2888.
† Osaka Dental University.
‡ Kanagawa University.
§ Tokyo Institute of Technology.
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10.1021/jo8013726 CCC: $40.75
Published on Web 10/28/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 9245–9250 9245

Makita et al.
linear molecular motor is also described based on this active
transport system.
Results and Discussion
We have studied the acylative neutralization of rotaxane
consisting of an ammonium salt axle and a crown ether wheel.10
The wheel migrates to the less crowded side on the axle in
the resulting rotaxane. Although the dethreading of the axle is
the thermodynamically favored process without the attractive
interaction between the wheel and the axle components, the
bulky end-caps at the end of the axle prevent the dethreading.
Based on this system, we designed an active transport system,
as illustrated in Figure 2.
At first, rotaxane has an asymmetric axle, where the end-
caps are small enough to allow the dethreading. The station
(an ammonium salt moiety) is located close to one of the two
end-caps, while there exists some space between the station and
the other end-cap (Figure 2a). Therefore, the gradient of the
potential surface around the station is also asymmetric; it is steep
for the proximate end-cap and gradual for the distant end-cap.
Due to the strong interaction between the station and the
wheel, ∆Gq for the dethreading is so large that dethreading is
prevented. During the treatment of rotaxane with a tertiary
amine, the wheel component starts migrating because the
interaction between the crown ether and the ammonium moiety
is lost (Figure 2b). Initially, the probability of the population
of the wheel component will be maximum at the center of the
axle because of the gradient of the potential surface; the tentative
position is independent of both the global thermodynamic
stability and the activation energy of the wheel dethreading. If
the system is kept in this condition, the wheel will be escaped
out over each end-cap with same probability.
When a bulky substituent is introduced on the amino group
by the rapid acylation reaction, the distribution of the wheel on
the axle component is fixed, and dethreading beyond the
proximate end-cap is selectively forbidden (Figure 2c). If the
acylation is slow, dethreading occurs at both the end-caps. For
a successful active transport that allows one-way migration, the
end-cap must be bulky enough to attenuate the thermal
dethreading and produce a steep potential surface before the
completion of acylation; however, it must be smaller than the
cavity of the wheel to allow dethreading to take place after
acylation.
To explore an appropriate end-cap group that allows active
transport, a series of rotaxanes with asymmetric axles were
synthesized and their acylation was examined (Scheme 1).
The distant end-cap was fixed to the 3,5-dimethylphenyl group.
Since this group is known to be so bulky that dethreading can
be completely prevented for the dibenzo-24-crown-8 (DB24C8)
wheel, the active transport can be detected easily.
FIGURE 1. Schematic representation of a [2]rotaxane-based unidi-
rectional linear molecular motor and its periodic potential surface. The
track has a polymeric structure and exhibits periodic potential surface.
Here, ∆Gbackward ) ∆Gforward ) 0, and the values of ∆Gq for both forward
and backward transpositions to the next station are identical.
indistinguishable. In other words, since every station on the track
interacts with the moving component with the same stability,
every station is thermodynamically identical (∆Gbackward
)
∆Gforward ) 0), and the activation energies (∆Gq) of the forward
and backward movements are exactly same. It seems that
unidirectional molecular motor can be realized if the moving
component interacts with the track to decrease ∆Gq
or
backward
∆Gqforward exclusively. However, this mechanism is contrary to
the second law of thermodynamics. Since unidirectional move-
ment is an entropically undesired change (∆S < 0), the supply
of free energy is necessary. If the moving component induced
the exclusive change in ∆Gq by any interaction, unidirectional
movement could take place without the additional supply of
free energy.9 Thus, the molecular motor must furnish an active
transport system in which thermodynamically unfavored change
is induced by a certain free energy source.
To achieve a unidirectional movement by the active transport,
a thermodynamically metastable state should be prepared by
the local gradient of the potential surface before it is kinetically
fixed.5f Most of the artificial molecular motors succeeded in
providing such a control on the basis of photoreactions.5b-e For
example, Leigh reported a linear active transport system,7b where
the wheel component of rotaxane was transferred toward a
thermodynamically undesired direction by the photo E-Z
isomerization of olefine. Natural molecular motors, however,
are driven by the action of ATP. Although active transport
systems were realized with the chemical energy in the rotational
system,5f-h only one example of a chemical-energy-based
artificial linear active transport system has been reported very
recently by Leigh.7c Leigh’s system is based on the asymmetric
acylation of a hydroxy group bearing [2]rotaxane. However,
the efficiency of active transport in this system is low; hence,
it seems difficult to construct a linear molecular motor that
moves on a long track using multiple chemical reactions.
To construct the active transport system with high efficiency,
we used [2]rotaxane system because wheel component and the
axle component are inseparable in rotaxane. Using rotaxane,
we can focus our effort to the construction of potential surface
on the axle as the track. In this paper, we wish to report a 100%
efficient active transport that is energized by a simple one-shot
acylation reaction of [2]rotaxane by providing the appropriate
potential surface on the axle component. The vision toward the
(10) (a) Kawasaki, H.; Kihara, N.; Takata, T. Chem. Lett. 1999, 1015–1016.
(b) Kihara, N.; Tachibana, Y.; Kawasaki, H.; Takata, T. Chem. Lett. 2000, 506–
507. (c) Tachibana, Y.; Kawasaki, H.; Kihara, N.; Takata, T. J. Org. Chem.
2006, 71, 5093–5104. In the case of rotaxanes with two stations on the axle, it
is known that the deprotonation of the ammonium moiety is fast; see: (d) Garaude,
S.; Silvi, S.; Venturi, M.; Credi, A.; Flood, A. H.; Stoddart, J. F. ChemPhysChem
2005, 6, 2145–2152.
(11) (a) Shibasaki, M.; Stoddart, J. F. Vo¨gtle, F. In Stimulating Concepts in
Chemistry; Wiley-VCH: Weinheim, 2000; pp 211-220. (b) Ashton, P. R.; Baxter,
I.; Fyfe, M. C. T.; Raymo, F. M.; Spencer, N.; Stoddart, J. F.; White, A. J. P.;
Williams, D. J. J. Am. Chem. Soc. 1998, 120, 2297–2307. (c) Chiu, S.-H.; Rowan,
S. J.; Cantrill, S. J.; Glink, P. T.; Garrell, R. L.; Stoddart, J. F. Org. Lett. 2000,
2, 3631–3634. (d) Jeppesen, J. O.; Becher, J.; Stoddart, J. F. Org. Lett. 2002, 4,
557–560. (e) Sohgawa, Y.; Fujimori, H.; Shoji, J.; Furusho, Y.; Kihara, N.;
Takata, T. Chem. Lett. 2001, 774–775.
(8) (a) Sauvage, J.-P.; Dietrich-Buchecker, C. Molecular Catenanes, Rotax-
anes, and Knots; Wiley-VCH: Weinheim, Germany, 1999. (b) Sauvage, J.-P.
Molecular Machines and Motors; Structure and Bonding; Springer: Berlin,
Germany, 2001; Vol. 99. (c) Balzani, V.; Credi, A.; Venturi, M. Concepts and
PerspectiVes for the Nanoworld, 2nd ed.; Wiley-VCH: Weinheim, Germany,
2008. (d) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F. Angew. Chem.,
Int. Ed. 2000, 39, 3349–3391.
(9) (a) Kelly, T. R.; Tellitu, I.; Sestelo, J. P. Angew. Chem., Int. Ed. Engl.
1997, 36, 1866–1868. (b) Kelly, T. R.; Sestelo, J. P.; Tellitu, I. J. Org. Chem.
1998, 63, 3655–3665.
9246 J. Org. Chem. Vol. 73, No. 23, 2008

QuantitatiVe ActiVe Transport in [2]Rotaxane
FIGURE 2. Concept of unidirectional transposition of the wheel component in rotaxane. (a) The crown ether wheel is trapped at the ammonium
station. (b) By neutralization of the ammonium group, the wheel component is released from the station. Due to the bulky end-cap, the wheel
tentatively migrates to the center of the axle. (c) Before the thermal nonselective dethreading of the axle component, a bulky acyl group is introduced
on the amino group to prevent dethreading beyond nitrogen.
SCHEME 1
TABLE 1. Result of N-Acylation and Dethreading of Rotaxanea
First, the cyclohexyl group was used as the proximate end-
cap (rotaxane 1a) because it is known to be slightly smaller
yield (%)b
efficiency of active transportc (%)
than the cavity of DB24C8.11 Although 1a was stable even at
353 K in CD3CN, deprotonative degradation started when it
was treated with 10 equiv of triethylamine at 333 K, thereby
forming 5a and DB24C8 (τ1/2 ) 1.3 h). Since deprotonated
rotaxane 2a could not be detected in the 1H NMR spectrum, it
can be concluded that deprotonation process is slow. We have
observed that deprotonation of ammonium-type rotaxane that
has only one station on the axle is very slow.10 Therefore, the
distribution of the wheel component on the axle is expected to
be fixed if the acylation is rapid.
1
3
DMAP (equiv)
4
6
1a 3p
1a 3p
1a 3p
1b 3p
1c 3p
1c 3q
1c 3r
0d
28 37
56 37
79 21
43
60
79
99
97
98
99
0.1
1.0
1.0
1.0
1.0
0
99
1
3
2
97 (88)
98 (92)
100 (95) NDe
a Initial concentration: [1] ) 15 mM. The reactions were carried out
at room temperature for 15 min in CD3CN in the presence of 5.0 equiv
of Et3N. b Determined by the 1H NMR spectra of the crude product
(isolated yield given in parentheses). c [4]/[4] + [6] d The reaction was
carried out for 24 h. e Not detected.
To drive the linear molecular motor by acylation, the
secondary ammonium group must be reproduced after one-step
transposition. Therefore, deprotectable acylation reagents were
used for the acylation experiments. If more than one independent
deprotection mode can be used, the linear molecular motor can
be designed easily. Thus, Boc2O (3p), 2,2,2-trichloroethoxy-
carbonyl chloride (TrocCl) (3q), and TFAA (3r) were used as
the acylation reagents because corresponding amide can be
quantitatively deprotected by acid, reduction, and base,
respectively.
When 1a was treated with 3p12 in CD3CN in the presence of
10 equiv of Et3N, rotaxane 4ap, in which the wheel component
migrated to the distant end-cap, was obtained in 28% yield,
while the dethreading product 6ap was obtained in 37% yield
(Table 1). Since acylation of free amine is rapid, neither 2 nor
5 was observed in the crude product. Since 4ap is thermody-
namically less stable than 6ap, the efficiency of active transport
was calculated to be 43%. To accelerate the acylation, 4-dim-
ethylaminopyridine (DMAP) was added to the system as a
catalyst. The yield of 4ap increased with the amount of DMAP
as expected. Therefore, the rapid acylation enhanced the
(12) (a) Cao, J.; Fyfe, M. C. T.; Stoddart, J. F. J. Org. Chem. 2000, 65,
1937–1946. (b) Chiu, S.-H.; Elizarov, A. M.; Glink, P. T.; Stoddart, J. F Org.
Lett. 2002, 4, 3561–3564.
J. Org. Chem. Vol. 73, No. 23, 2008 9247

Makita et al.
-
FIGURE 3. Crystal structure of 1b and 4cr obtained by X-ray crystallographic analysis. (a) ORTEP drawing of 1b. Hydrogens and PF6 were
omitted for clarity. (b) ORTEP drawing of 4cr. Hydrogens were omitted for clarity.
SCHEME 2
efficiency of active transport. However, 6ap was still obtained
even when 1 equiv of DMAP was used.
of 1c to form 5c is a thermodynamically favored process in the
presence of triethylamine. Since 1d10 is stable under the same
condition, it is evident that the wheel component in 2c
dethreaded the axle component beyond the neopentyl-type end-
cap, but not beyond the 3,5-dimethylphenyl end-cap. Therefore,
the migration of the wheel component toward the proximate
end-cap is thermodynamically favored movement for 1c during
the treatment with triethylamine. However, in the acylation
experiments, the wheel in 1c migrated toward the distant end-
capsa thermodynamically undesired directionsto produce 4cr
quantitatively. Therefore, the movement is the active transport,
which was achieved by the local potential surface on the axle
of 1c and 2c.The effect of the neopentyl-type group as the distant
end-cap was examined. Thus, rotaxane 7 having neopentyl-type
distant end-cap was prepared (Scheme 2).13 Rotaxane 7 was
stable even at 333 K in DMSO that strongly inhibits the
hydrogen bonding interaction. Due to the hydrogen bonding
interaction that was working between wheel and axle even in
DMSO, the neopentyl group acted as the effective end-cap.14
Acylative neutralization of 7 by benzoyl chloride afforded the
corresponding rotaxane 8.
Dethreading of 8 occurred rapidly at 333 K in CD3CN to
form 9 and DB24C8 (τ1/2 ) 1.2 h) in the absence of
triethylamine. These results indicate the diversed effect of the
neopentyl-type group as the distant end-cap. When the interac-
tion between the axle and the wheel is working, the neopentyl
group acts as the sufficiently bulky end-cap to produce the steep
potential. However, without the intercomponent interaction, the
neopentyl-type group behaves as the sufficiently small end-cap
to allow the dethreading of the wheel component.
To produce a steeper potential surface, a more bulky tert-
butyl group was employed as the proximate end-cap (rotaxane
1b).13 The structure of 1b, as determined by X-ray crystal-
lographic analysis, is shown in Figure 3a. Owing to the bulkiness
of the tert-butyl group, the deprotonative degradation of 1b was
very slow (τ1/2 ) 198 h at 333 K) in the presence of 10 equiv
of triethylamine. 1b was then treated with 3p in the presence
of triethylamine, and 4bp was obtained in 99% yield along with
only 1% of 6bp. As expected, the slow dethreading due to a
steeper potential surface in 2b drastically prevented the forma-
tion of 6bp to improve the efficiency of the active transport.
Encouraged by this result, a neopentyl-type end-cap group
that is suitable for the construction of a polymeric track with a
periodic potential was employed as the proximate end-cap
(rotaxane 1c). As expected, the neopentyl-type end-cap in 1c
and the tert-butyl group in 1b behaved similarly, and a good
yield of the desired rotaxane 4cp was obtained in the reaction
with 3p. For faster acylation, other acylation reagents were
examined. The selectivity of 4c increased slightly with 2,2,2-
trichloroethoxycarbonyl chloride (TrocCl) (3q), and the quan-
titative formation of 4cr was achieved when TFAA (3r) was
used as the acylation reagent. Owing to the high reactivity of
3r, the addition of DMAP was not necessary. The structure of
4cr was confirmed by X-ray crystallographic analysis, as shown
in Figure 3b.
The simple first order kinetics (τ1/2 ) 462 h at 333 K in
CD3CN) was followed by the deprotonative decomposition of
1c that was caused by treating it with 10 equiv of triethylamine
to produce 5c. Therefore, it was confirmed that the dethreading
(14) Tachibana, Y.; Kihara, N.; Furusho, Y.; Takata, T. Org. Lett. 2004, 6,
4507–4509.
(13) Makita, Y.; Kihara, N.; Takata, T. Chem. Lett. 2007, 102–103.
9248 J. Org. Chem. Vol. 73, No. 23, 2008

QuantitatiVe ActiVe Transport in [2]Rotaxane
FIGURE 4. Schematic representation of the unidirectional migration of the wheel component on a polymeric track. (a) The linear molecular motor
consists of [2]rotaxane in which the axle is made of polyammonium salt, and every ammonium salt moiety is separated by a neopentyl group. The
ammonium salt moieties on the axle track are alternatively acylated by the Boc group (light blue) and the TFA group (green). (b) The Boc group
is deprotected in order to reproduce the ammonium salt moiety. The wheel component migrates to the thermodynamically stable ammonium salt
station. (c) The ammonium groups are acylated by Boc (one-shot acylation). The wheel component unidirectionally migrates to the space between
the Boc and the neopentyl groups. (d) The selective deprotection of the TFA group is followed by application of protonation forces to the wheel
component in order to move it to the thermodynamically stable ammonium salt station. (e) The ammonium group is acylated by TFAA (one-shot
acylation). The wheel component unidirectionally migrates to the space between the TFA and the neopentyl groups.
Conclusions
The active transport of the wheel was driven by a one-shot
acylation reaction that corresponded to the phosphorylation by
ATP. Therefore, the present work demonstrates that the features
of natural molecular motors can be realized in simple molecular
systems by a simple reaction that utilizes the local potential
surface. We are currently focusing our efforts toward the
synthesis of poly[2]rotaxane, which behaves as a linear molec-
ular motor.
We have investigated the quantitative active transport of the
wheel component of rotaxane. The transport of the wheel is
controlled by a neopentyl end-cap. The direction of transport
is influenced by the local potential surface and not by the
thermodynamic stability. In other words, it is driven by the
gradient of the local potential surface and the free energy due to
acylation and not as a result of attractive interactions. These
features are an essential part of chemical energy-driven unidi-
rectional linear molecular motors. Thus, an artificial linear
molecular motor system can be envisioned to be a simple
extension of the transport system illustrated in Figure 4.
The designed unidirectional linear motor consists of [2]ro-
taxane with a polymeric ammonium salt axle. The ammonium
salt moieties are separated by neopentyl groups and are
alternatively protected by two types of independent deprotectable
acyl groups such as Boc and TFA. This system is referred by
the alternating copolymer of 4 cp and 4cr. When a Boc group
(light blue protection) is selectively deprotected by acid, the
wheel component moves in a unidirectional manner to the next
ammonium moiety beyond the neopentyl group. The resulting
ammonium rotaxane is also protected by Boc. We have
demonstrated that the wheel component can undergo quantitative
active transport because of the steep potential surface created
by the neopentyl group. The next step is the selective depro-
tection of TFA by alkaline hydrolysis, which is followed by
protonation in order to force the wheel to migrate to the next
ammonium group in a unidirectional manner. We can expect
that the treatment of the resulting rotaxane by TFAA results in
the recovery of the first condition of the linear molecular motor
although the wheel component unidirectionally forwarded two
steps.
Experimental Section
1
Rotaxane (1a): H NMR (500 MHz,CDCl3) 7.67 (s, 2H), 7.55
(d, J ) 8.3 Hz, 2H), 7.36 (d, J ) 8.3 Hz, 2H), 7.21 (s, 1H), 7.05
(brs, 2H), 6.92-6.85 (m, 8H), 5.31 (s, 2H), 4.70-4.67 (m, 2H),
4.25-4.22 (m, 4H), 4.12-4.09 (m, 4H), 3.84-3.76(m, 8H),
3.60-3.56 (m, 4H), 3.33-3.30 (m, 4H), 2.89-2.86 (m, 2H), 2.37
(s, 6H), 1.54-1.23 (m, 6H), 0.94-0.90 (m, 3H), 0.60-0.57 (m,
2H); 13C NMR (125 MHz, CDCl3) δ 166.7, 147.7, 138.3, 137.8,
135.0, 132.4, 130.5, 123.0, 128.1, 127.5, 122.0, 113.1, 70.9, 70.3,
68.6, 65.9, 55.6, 52.6, 35.9, 30.4, 25.8, 25.5, 21.3; mp 69-70 °C;
HRMS (ESI-TOF) calcd for C48H64N1O10 814.4530 ([M - PF6]+),
found814.4523 [M - PF6]+. Anal. Calcd for C48H64F6NO10P: C,
60.05; H, 6.72; N, 1.46. Found: C, 59.69; H, 6.47; N, 1.25.
1
Rotaxane (1b): H NMR (500 MHz,CDCl3) δ 7.69-7.67 (m,
4H), 7.37 (d, J ) 8.3 Hz, 2H), 7.21 (s, 1H), 6.94-6.87 (m, 10H),
5.33 (s, 2H), 4.72-4.70 (m, 2H), 4.29-4.25 (m, 4H), 4.15-4.11
(m, 4H), 3.81-3.75 (m, 8H), 3.60-3.57 (m, 4H), 3.30-3.27 (m,
4H), 3.03-3.00 (m, 2H), 2.36 (s, 6H), 0.76 (s, 6H); 13C NMR (125
MHz, CDCl3) δ 166.7, 147.8, 138.3, 138.1, 131.7, 131.3, 130.0,
128.0, 127.5, 122.0, 113.1, 71.1, 70.5, 68.6, 65.9, 61.5, 53.7, 30.4,
27.1, 21.3; mp 188-189 °C; HRMS (ESI-TOF) calcd for
C46H62N1O10 788.4368 ([M - PF6]+), found 788.4366 [M - PF6]+.
Rotaxane (1c): 1H NMR (500 MHz, CDCl3) δ 7.95 (d, 2H, 8.3
Hz), 7.66 (s, 2H), 7.61 (d, 2H, 8.3 Hz), 7.36-7.20 (m, 5H),
6.93-6.84 (m, 10H), 5.29 (s, 2H) 4.75-4.72 (m, 2H), 4.29 (s, 2H),
J. Org. Chem. Vol. 73, No. 23, 2008 9249

Makita et al.
4.22-4.20 (m, 4H), 4.11-4.08 (m, 4H), 3.91 (s, 3H), 3.77-3.72
(m, 8H), 3.59-3.56 (m, 4H), 3.33-3.27 (m, 6H), 2.97 (s, 2H),
2.35 (s, 6H), 0.86 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 167.0,
166.7, 147.7, 143.5, 138.3, 137.9, 135.0, 131.7, 131.1, 129.9, 129.7,
129.5, 128.4, 127.9, 127.4, 127.3, 121.9, 112.9, 77.6, 72.6, 71.0,
70.4, 68.4, 65.9, 58.0, 53.8, 52.2, 34.7, 22.1, 21.3; mp 149-150
°C; HRMS (FAB-MS) calcd for C55H70NO13 952.4842 ([M -
3.70-3.60 (m, 8H), 3.23-3.12 (m, 8H), 2.85-2.80 (m, 4H), 2.20,
2.19 (two s, 6H), 0.93-0.94 (m, 6H); 13C NMR (125 MHz, CDCl3)
δ 167.1, 148.6, 137.9, 131.0, 129.8, 129.2, 129.0, 128.3, 127.1,
126.5, 120.6, 111.6, 72.7, 69.7, 69.4, 69.3, 68.0, 66.8, 52.2, 38.1,
24.0, 23.8, 20.9; mp 48-50 °C; HRMS (FAB-MS) calcd for
C58H70Cl3NO15 1125.3811 ([M]+), found 1125.3822 ([M]+). Anal.
Calcd for C58H70Cl3NO15: C, 61.78; H, 6.26; N, 1.24. Found: C,
61.42; H, 6.06; N, 1.42.
PF6]+), found 952.4856 [M
-
PF6]+. Anal. Calcd for
N-Acylated rotaxane (4cr): 1H NMR (500 MHz, CDCl3) δ 8.20
(d, 2H, J ) 8.3 Hz), 8.11 (s, 2H), 7.98 (d, 2H, J ) 8.3 Hz), 7.33
(d, 2H, J ) 8.3 Hz), 7.10 (s, 1H), 6.88-6.81 (m, 8H), 5.97 (s,
2H), 4.52 (s, 2H), 4.51 (s, 1H), 4.09-4.01 (m, 4H), 3.89 (s, 3H),
3.71-3.68 (m, 4H), 3.61-3.58 (m, 4H), 3.42-3.21 (m, 4H), 3.17
(s, 2H), 3.16 (s, 2H), 2.84-2.81 (m, 4H), 2.22 (s, 6H), 0.94 (s,
6H); 13C NMR (125 MHz, CDCl3) δ 168.7, 168.6, 167.4, 148.6,
148.6, 145.6, 138.7, 138.3, 137.9, 137.7, 134.4, 130.9, 129.5, 129.5,
129.3, 129.2, 129.1, 128.6, 128.5, 126.5, 126.1, 125.6, 124.2, 120,7,
120.5, 113.0, 111.6, 111.4, 106.4, 69.8, 69.6, 69.4, 68.1, 67.6, 50.9,
47.8, 29.9, 24.5, 21.7, 21.5, 21.4, 21.0; mp 126-127 °C; HRMS
(FAB-MS) calcd for C57H68F3NO14 1047.4592 ([M]+), found
1047.4606 ([M]+).
C55H70F6NO13P: C, 60.16; H, 6.43; N, 1.28. Found: C, 59.96; H,
6.23; N, 1.26.
General Procedure for the Neutralization-Induced Dethread-
ing of Rotaxane. A solution of rotaxane (5.4 µmol) and triethy-
lamine (7.0 µL, 54 µmol) in CD3CN (0.60 mL) was allowed to
stand at 60 °C. The progress of the dethreading was monitored by
1H NMR.
General Procedure for N-Acylation. A solution of rotaxane
(5.4 µmol), acylation reagent (0.54 mmol), triethylamine (7.0 µL,
54 µmol), and DMAP (0.7 mg, 0.54 µmol) in CD3CN (0.60 mL)
was allowed to stand at room temperature for 0.5 h. After water
was added, the mixture was extracted by chloroform. The organic
layer was dried over magnesium sulfate and evaporated in vacuo.
The crude product was purified by preparative gel permeation
chromatography (chloroform) to afford N-acylated rotaxane and the
dethreading product.
Rotaxane (7)13: 1H NMR (500 MHz, CDCl3) δ 7.56 (brs, 2H),
7.35 (d, 2H, J ) 8.3 Hz), 7.20 (d, 2H, J ) 8.3 Hz), 6.91-6.88 (m,
4H), 6.84 (s, 1H), 6.81-6.79 (m, 4H), 5.01 (s, 2H), 4.66-4.63
(m, 2H), 4.46-4.44 (m, 2H), 4.11-4.10 (m, 8H), 3.78-3.77 (m,
8H), 3.63 (s, 3H), 3.50-3.43 (m, 8H), 2.49 (s, 2H), 2.42 (s, 2H),
1.10 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 172.4, 171.7, 147.6,
138.5, 137.5, 131.7, 131.5, 130.8, 129.7, 128.2, 126.8, 121.8, 112.8,
70.8, 70.3, 68.3, 65.3, 52.8, 52.4, 51.4, 45.1, 32.8, 27.7, 21.3; mp
48-49 °C; HRMS (ESI-TOF) calcd for C49H66NO12 860.4580 ([M
- PF6]+), found 860.4561 [M - PF6]+. Anal. Calcd for
C49H66F6NO12P: C, 58.50; H, 6.61; N, 1.39. Found: C, 58.50; H,
6.94; N, 1.55.
1
N-Acylated rotaxane (4bp): H NMR (500 MHz, CDCl3) δ
8.16-8.11 (m, 4H), 7.09 (s, 1H), 7.00-6.94 (m, 2H), 6.89-6.81
(m, 8H), 5.98 (two s, 2H), 4.66, 4.37 (two s, 2H), 4.10-4.03 (m,
8H), 3.73-3.71 (m, 4H), 3.64-3.62 (m, 4H), 3.27-3.23 (m, 4H),
2.96-2.85 (m, 6H), 2.21 (s, 6H), 1.51, 1.49 (two s, 9H), 0.92, 0.89
(two s, 9H); 13C NMR (125 MHz, CDCl3) δ 167.2, 148.6, 137.8,
134.2, 129.4, 129.3, 128.4, 127.3, 126.6, 125.1, 120.6, 111.6, 84.5,
69.7, 69.5, 69.4, 68.0, 66.9, 57.4, 53.4, 52.7, 34.3, 33.8, 28.5, 28.4,
27.7, 21.0; mp 96-98 °C; ESI-MS m/z 910.10 [M + Na]+. Anal.
Calcd for C51H69NO12: C, 68.97; H, 7.83; N, 1.58. Found: C, 68.68;
H, 7.58; N, 1.45.
N-Acylated rotaxane (8): 1H NMR (500 MHz, CD3CN, 333K)
δ 7.87 (d, 2H, J ) 7.8 Hz), 7.41-7.37 (m, 6H), 6.93-6.87 (m,
10H,), 6.76 (brs, 2H), 5.66 (s, 2H), 4.38 (brs, 4H), 4.13-4.03 (m,
8H), 3.69-3.63 (m, 8H), 3.53 (s, 3H), 3.39-3.34 (m, 4H), 3.07
(brs, 4H), 2.41 (s, 2H), 2.30 (s, 2H), 2.25 (s, 6H), 0.89 (brs, 6H).
Decomposition of Rotaxane (8).14 A solution of rotaxane 8 (5.4
µmol) in CD3CN (0.60 mL) was allowed to stand at 333 K. The
N-Acylated rotaxane (4cp): 1H NMR (500 MHz, CDCl3) δ 8.15,
8.14 (two s, 2H), 8.10 (brs s, 2H), 8.00-7.98 (m, 2H), 7.35-7.33
(m, 2H), 7.07 (m, 2H), 7.03-6.94 (m, 2H), 6.86-6.79 (m, 8H),
4.54, 4.44 (two s, 2H), 4.42, 4.33 (two s, 2H), 4.08-4.01 (m, 8H),
3.90, 3.89 (two s, 2H), 3.72-3.60 (m, 8H), 3.27-3.23 (m, 4H),
3.17, 3.04 (two s, 2H), 3.13, 3.11 (two s, 2H), 2.90-2.86 (m, 4H),
2.20 (s, 6H), 1.48, 1.48 (two s, 9H), 0.95, 0.91 (two s, 9H); 13C
NMR (125 MHz, CDCl3) δ 167.2, 167.1, 148.6, 137.7, 134.2, 134.0,
131.0, 129.8, 129.5, 129.4, 128.4, 127.2, 127.2, 127.1, 126.4, 120.6,
111.6, 84.6, 72.7, 72.6, 69.7, 69.5, 69.4, 68.0, 66.9, 53.8, 53.1, 53.0,
52.4, 52.2, 38.1, 37.7, 29.9, 27.7, 23.8, 23.7, 21.0; mp 58-59 °C;
HRMS (FAB-MS) calcd for C60H77NNaO15 1074.5185 ([M +
Na]+), found 1074.5145 ([M + Na]+).
1
progress of the dethreading was monitored by H NMR.
Acknowledgment. This work was funded by the Sasakawa
Scientific Research Grant from The Japan Science Society.
Supporting Information Available: Experimental details,
spectroscopic and analytical data for new compounds, and X-ray
crystallographic files (CIF) for rotaxane 1b and 4cr. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
N-Acylated rotaxane (4cq): H NMR (500 MHz, CDCl3) δ
8.19-8.16 (m, 2H), 8.11-8.08 (m, 2H), 8.00-7.98 (m, 2H),
7.38-7.33 (m, 2H), 7.09-7.07 (m, 1H), 7.03-6.98 (m, 2H),
6.89-6.80 (m, 8H), 5.97, 5.96 (two s, 2H), 4.69, 4.54 (two s, 2H),
4.50-4.40 (m, 4H), 4.10-4.01 (m, 8H), 3.90, 3.88 (two s, 3H),
JO8013726
9250 J. Org. Chem. Vol. 73, No. 23, 2008