Effective Synthesis and Modification of α-Cyclodextrin-Based [3]Rotaxanes Enabling Versatile Molecular Design

Article abstract of DOI:10.1002/ejoc.201900362

One-pot synthesis of various α-cyclodextrin-(α-CD-) based [3]rotaxanes in water and their structural modifications are discussed in detail. Pseudo[3]rotaxane was prepared from α-CD and α,ω-diaminododecane in water (above 100 g, quantitative yield in a 1 L

Full text of DOI:10.1002/ejoc.201900362

A Journal of
Accepted Article
Title: Effective Synthesis and Modification of α-Cyclodextrin-Based
[3]Rotaxanes Enabling Versatile Molecular Design
Authors: Yosuke Akae, Hiromitsu Sogawa, and Toshikazu Takata
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900362
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10.1002/ejoc.201900362
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a
Effective Synthesis and Modification of -Cyclodextrin-Based
[3]Rotaxanes Enabling Versatile Molecular Design
Yosuke Akae, Hiromitsu Sogawa, and Toshikazu Takata*
Abstract: One-pot synthesis of various a-cyclodextrin-(a-CD-) based
[3]rotaxanes in water and their structural modifications are discussed
in detail. Pseudo[3]rotaxane was prepared from a-CD and a,w-
diaminododecane in water (above 100ꢀg, quantitative yield in a 1ꢀL
flask). Successive urea-forming end-capping reactions with
isocyanate in water selectively afforded [3]rotaxane with head-to-
head structured a-CDs. The yields were varied by bulkiness and
functionality of end-capping agents. Significant modifications of the
axle end and wheel OH group of the [3]rotaxanes were performed by
the Suzuki coupling with arylboronic acids and by the perfect acylation
with acid anhydrides, respectively.
However, such requirement significantly restricts the purposive
molecular design of CD-based rotaxanes despite its usefulness.
Meanwhile, we previously developed a urea-forming end-capping
method for high-yielding synthesis of a-CD-based [3]rotaxane,
which actually overcame the above synthetic limitation.[7] Namely,
the end-cap reaction of a-CD-based pseudorotaxanes having
a,w-diaminoalkane axles efficiently proceeds in water under
heterogeneous conditions which allows the use of several
aromatic isocyanates without any hydrophilic groups such as 3,5-
dimethylphenyl isocyanate. Possible side reactions such as
hydrolysis of isocyanate and the reaction of OH group were well
controlled to give high yields of the rotaxanes. To enhance the
applicability of this protocol for the effective synthesis of CD-
based rotaxanes, the systematic study to clarify the structural
requirement of the end-cap agents should be needed. Herein we
report in detail the scope and limitations of the synthetic protocol
using isocyanate end-cap agents in the urea end-capping
reactions. In addition, functionalization and modification of the
[3]rotaxanes are also discussed in this work to expand the
usefulness of the [3]rotaxanes (Figure 1).[8]
Introduction
Various synthetic methods of rotaxanes have hitherto been
developed to enable the elaborate designs of sophisticated
supramolecular architectures.[1,2] Cyclodextrin (CD), a typical
wheel component of rotaxane, is widely used to construct unique
frameworks, including polyrotaxane, polyrotaxane networks,
polymer molecular wires, and biocompatible materials.[3,4] In
addition to these polymeric materials, CD-based low molecular
weight scaffolds were studied not only for their synthetic interest
but also for their application to probes and building blocks for
molecular machines.[5] These applications are based on the
characteristic structure of CDs, which consists of several glucose
units connected in a circular fashion. Meanwhile, synthesis of CD-
based rotaxanes is not a simple work, being suffering from the
following limitations in molecular design. The most common
synthetic method of CD-based rotaxanes is the axle end-cap of
pseudorotaxane. In this method, inclusion complex from CD and
axle component which was initially formed was treated with bulky
end-cap agent to yield the target rotaxane molecule. In this
procedure, a highly polar or hydrophilic solvent is required, as
CDs incorporate guest molecules in their cavities by the
hydrophobic interaction. In the typical synthesis of rotaxanes,
polar organic solvents such as DMF, DMSO, and methanol are
used instead of water, but the yield is usually low due to the
weakened solvophobic interaction. Therefore, the reaction in
polar solvent often requires bulky hydrophilic end-cap agents
such as 3,5-dicarboxyphenyl, sulfonyl naphthyl, and CD itself.[6]
Figure 1. The synthetic concept of this work.
Results and Discussion
Scalable Selective Synthesis of
via the Urea End-Capping Method
a
-CD-Based [3]Rotaxanes
a-CD-based [3]rotaxanes were synthesized as depicted in
Scheme 1.[7] A wide range of capping agents were tried here to
increase the diversity of axle end structures, focusing particularly
on the size effect of bulky end-capping groups. The states of the
reagents are given beside the compounds’ numbers. Those with
no annotation are liquids. Initially, the typical procedure was
adjusted to 22 capping agents (Table 1, Figure S4). Namely,
1,12-diaminododecane and a-CD were mixed in water at reflux
temperature for 1 hour to give a homogeneous solution, which
was then left to stand overnight at ambient temperature to give
pseudo[3]rotaxane P1 as a block crystal. Note that large-scale
synthesis (100ꢀg) could be easily realized using a simple
purification protocol involving filtration and washing with water.
The obtained pseudo[3]rotaxane P1 was then dispersed in water,
followed by the addition of the capping agents to this
Dr. Y. Akae, Dr. H. Sogawa, Prof. T. Takata
Department of Chemical Science and Engineering
Tokyo Institute of Technology
2-12-1, O-okayama, Meguro-ku, Tokyo 152-8552 (Japan)
Fax: (+81) 03-5734-2888
E-mail: ttakata@polymer.titech.ac.jp
HP: http://www.op.titech.ac.jp/polymer/lab/takata/japanese/index-
j.html
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201900362
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heterogeneous solution. The reaction temperature was basically
set at 0 °C to prevent side reactions such as isocyanate addition
to the hydroxyl groups on CD. However, the reaction was
operated at room temperature for solid cap reagents 6, 7, 8 and 9
as these end cap reagents did not afford the corresponding
rotaxanes at low temperature. The above mentioned reactions
can be performed in one pot; however, in this work, we used a
prerequisite amount of P1 for the end-capping study after
preparing this on a large scale. After standard purification,
[3]rotaxanes, caps 1–10, were obtained, whereas other capping
agents (11–22) afforded no rotaxanes (Table 1, Figure S4). We
have to note that some of the [3]rotaxanes such as R1 and R2
exhibited size-complementary feature. They were stable enough
to be isolated at room temperature and have the medium stability
between ‘’rotaxane’’ and ‘’pseudo-rotaxane’’ as the size of the
axle end group is similar to that of the wheel cavity.[9] Size-
complementarity is especially important when we discuss its
unique dissociation behavior. Thus, we simply call every
rotaxanes isolated by the end-capping reaction as ‘’rotaxane’’ in
this manuscript to avoid the complicated description.
and a higher field shift of O(3)H around 5-6ꢀppm were observed
as characteristic shifts of the head-to-head [3]rotaxane structure
(for other [3]rotaxanes, see ESI). These shifts were probably due
to initial intramolecular hydrogen bonding within single a-CD
molecules changing to intermolecular bonds between two CD
units in [3]rotaxanes. Larger shifts were observed in [3]rotaxanes
obtained from shorter axles, such as 1,10-diaminododecane. The
same tendency was observed when we applied ortho-substituted
(1, 2, 4, 5, 6, 7 and 10) rather than meta-substituted phenyl
isocyanates (3, 8 and 9). These results indicate that a shorter
distance between two CD units induces large chemical shifts.
Additionally, compared with the dumbbell and [3]rotaxane, only
the g proton of urea shifted upfield from 6.8 to 6.3 ppm, whereas
other benzene signals of axle ends remained with slight shifts.
This upfield shift was probably derived from the difference in
hydrogen bonding interaction between [3]rotaxane and single
dumbbell compound. Single dumbbell could has a hydrogen
bonding between urea N–H bond and solvent DMSO. However,
in [3]rotaxane, this urea N–H would form the hydrogen bonding
with hydroxyl group of CD moiety, caused the different chemical
shift. Meanwhile, the X-ray structure analysis gave the distance
between two CD units as 2.7–2.9ꢀÅ, clearly indicating the
existence of hydrogen bonds. Besides, out of six primary hydroxyl
groups of one CD unit on the narrower rim side, five pointed
outside and one pointed inside, which sounded interact urea
bonds of the dumbbell. Their interaction distances were around
3ꢀÅ, and the configuration indicated the presence of N–H...O
bonds between urea N–H and the hydroxyl groups. In this crystal
structure, benzene rings and bromo substituents exhibited no
interactions with other moieties, even in the intermolecular region.
Specifically, both 1H NMR and X-ray structure analysis were
consistent with respect to the hydrogen bonds between two CD
units, as well as those between the urea and the hydroxyl groups
of CD. Furthermore, it is noteworthy that no shifts of O(3)H, O(2)H
of CD, or the g proton of urea were observed for [2]rotaxanes R11
and R12, which was prepared via a deslipping reaction from
[3]rotaxane R1 and R2, respectively (for the structures of R11 and
R12, see ESI). This observation also verified that these shifts
originated from the head-to-head structure of [3]rotaxane.
When we considered ineffective capping reagents for this reaction
(1–10 in Table 1 versus 11–22 in Figure S4), several important
insights were elucidated. The details were described in ESI,
section 3. Besides, when we focus on rotaxane-affording capping
agents, it can be concluded that they have well-balanced
substituents, which are bulky enough to function as stoppers, but
not too large to decrease the reactivity of the isocyanate. Even
among these capping agents, the yield from 2,6-dimethylphenyl
isocyanate 4 was lower than that from 3,5-dimethyl 3 because of
the steric hindrance to the isocyanate moiety. Meanwhile, liquids
1–5 tended to show higher yields than solids 6–10. This was
because the liquid capping agents dispersed more effectively
than the solid ones in this heterogeneous system. This proposal
was also supported by the results that solid agents 21 and 22,
gave no rotaxanes (Figure S4). In addition, the yields tended to
increase by improving the dispersity of solids caps 8, 9 and 10
(For details, see section 4 in ESI). Briefly, 10 afforded [3]rotaxane
in as high a yield as with liquids 1, 2, and 3 (69% versus 60–70%)
Scheme 1. Synthesis of [3]rotaxanes via the urea end-capping method.
OH
O
O
6
OH
HO
α-CD (200 mol%)
H2N
(CH2)12
NH2
H2N (CH2)12 NH2
1) H2O, reflux, 1 h
2) r. t., stand 12 h
pseudo[3]rotaxane P1
NCO
X
(5.0 eq.)
O
H
N
H
N
X
(CH2)12
N
H
N
H
H2O
X
0 °C, 1 h
O
[3]rotaxane R1–R10
Table 1. Chemical structures of capping agents and yields of [3]rotaxanes.
NCO
OCF3
End cap
agent
NCO
NCO
OMe
NCO
NCO
Br
1
2
3
4
5
[3]rotaxane
(Yield%)
R1(73)a R2(64)a
R3(60)a
R4(13)a R5(50)
Br
Br
Br
Br
NCO
NO2
End cap
agent
NCO
OMe
NCO
OMe
NCO
I
NCO
6 (solid)
7 (solid)
R7(12)b
8 (solid)
9 (solid)
10 (solid)
R10(21)
[3]rotaxane
(Yield%)
R6(9.6)b
R8(4.3)b
R9(16)b, c
aThese data have been reported in reference 7c. bThe reaction was performed
at room temperature. cOvernight reaction
Every obtained [3]rotaxane had a head-to-head structure owing
to hydrogen bonding between two CD units as verified by 1H NMR
and X-ray crystal structure analysis (Figures. S2 and S5).[7c] In
1
the H NMR spectrum of R2, a lower field shift of O(2)H for CD
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10.1002/ejoc.201900362
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at optimized condition. These results suggested not only simple
bulkiness but also the dispersity in water of capping agents is
important for our developed system. Finally, different capping
candidates, other than isocyanate, including 3,5-dimethylphenyl
aldehyde 23, fluoro-group-substituted 24, and 25, were also
examined, but unfortunately, they were ineffective in this system
(see ESI).
column chromatography and preparative GPC could be applied.
Finally, we selected the following route: bromo substituents were
introduced into the phenyl moieties of the axle ends of rotaxane
via N-bromosuccinimide (NBS), followed by transition-metal-
catalyzed cross-coupling reactions, including Suzuki coupling.
Initially, bromination of the axle ends of [3]rotaxane was studied
(Scheme 2). [3]Rotaxane R2 was mixed with a slight excess of
NBS in DMF. This was purified by reprecipitation into water,
followed by washing with water and acetone. In this reaction, we
first assumed the bromination at the para position of methoxy
group, which is strong electron-donating group, would take place.
But, the reaction proceeded at the para position of the urea group,
selectively. The substitution position was elucidated by comparing
the NMR spectra of R6 and R7. Note that the substitution position
did not change when the single dumbbell molecule without any
CD was treated under the same conditions, indicating that this
result is not specific case for rotaxane. DFT calculation of model
compound was performed to gain the information about the
substitution position. However, calculated electron density of the
para position for the urea group and methoxy group was almost
same. indicating that the bromination could be happened at either
positions without any selectivity (More detail for DFT calculation,
see ESI and Figure S3).[10] R7 was also obtained by direct urea
end capping with capping agent 7, but bromination of R2 afforded
a higher yield (12% versus 62%) with no unexpected byproducts.
The stepwise modification route was more effective than the direct
end capping reaction. This is probably because liquid cap 2 was
more suited for our developed end-capping method compared to
solid cap 7 in terms of higher water dispersity. Meanwhile,
dibromo substitution at one phenyl ring failed to proceed.
Furthermore, this para bromination via NBS was applied in a
similar manner to [3]rotaxane R1 having bromophenyl axle ends
and to [3]rotaxane R10 having nitrophenyl ones under harsher
reaction conditions.
Axle End Modification via Bromination Followed by Suzuki
Coupling
To expand the further versatility of molecular design, modification
of the currently obtained rotaxanes via urea end capping is also a
reasonable functionalization method. Firstly, a methodology for
modifying axle ends was then studied. In order to determine the
synthetic strategy, the following five points should be considered.
(1) The decomposition of components, such as urea bonds and
glucose, must be prevented. Heating above 120 °C could induce
gradual decomposition of urea in this rotaxane and should be
avoided. (2) The deslipping reactions of size-complementary
rotaxanes induced by heating had to be considered. The tolerant
temperature depended on the rotaxane structures.[7b,c] (3) For the
native CD-based rotaxane studied here, the solvent candidates
were limited and included DMF, DMSO, and pyridine, because of
its poor solubility in other solvents. (4) The obtained [3]rotaxane
was also soluble in a narrow range of solvents; the products then
required purification via the limited methods available with these
solvents, such as washing and reprecipitation. Another reason for
this purification limit was that heating during drying under a
reduced pressure to eliminate the solvent was often accompanied
by
a deslipping reaction as mentioned above. (5) The
[3]rotaxanes contained 36 hydroxyl groups and two functionalized
dumbbell. When these multiple functional groups partially react,
their separation can become extremely difficult. Thus, the
modification reaction needed to be complete. Considering the
above synthetic limitations, neutral or relatively mild reactive
conditions might be preferred rather than nucleophilic attack by
generating strong anions. Meanwhile, it should be noted that
when the rotaxanes became soluble in common organic solvents
via wheel modification, purification methods such as silica gel
The obtained [3]rotaxane R7 was then used for Suzuki coupling
(Scheme 2). The reaction proceeded to completion as expected
to give [3]rotaxane R13. This showed a deslipping behavior when
heated to 100°C in DMSO, indicating its potential as a building
block for a stimuli-responsive supramolecular framework.[11]
Scheme 2. Modification of axle ends of [3]rotaxane.
A) Bromination
Br
H H
N N
O
NBS (1.1 eq.)
H H
N N
O
OMe
Br
OMe
O
N N
H H
O
N N
H H
DMF, r. t., 12 h
97%
MeO
MeO
[3]rotaxane R7
[3]rotaxane R2
B) Suzuki-coupling
B(OH)2 (10 eq.)
K2CO3 (10 eq.)
O
O
Br
O
Pd(PPh3)4 (10 mol%)
H H
N N
O
H H
N N
O
OMe
Br
OMe
O
N N
MeO
H H
N N
H H
DMF/ H2O = 5/ 1
80 °C, 18 h
95%
MeO
O
[3]rotaxane R7
[3]rotaxane R13
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The synthetically most crucial point was using excess
phenylboronic acid (10 eq.). When this was reduced to 5 eq., a
mixture of R7 and a partially reacted byproduct, which was difficult
to purify, was obtained after reacting for one day. Several
phenylboronic acids were applicable to this reaction, such as 3-
carbamoyl-, 3,5-dimethyl-, 3-hydroxyl-, 3-formyl-, and 3-nitro-
substituted phenylboronic acid and 1-pyreneboronic acid to give
the corresponding rotaxanes R14, R15, R17, R18, R19, and R16,
respectively (Table 2). However, boronic pinacol esters were
ineffective, probably because of their low reactivity and
hydrophobicity. Successive bromination followed by Suzuki
coupling was also achieved for [3]rotaxanes R1 and R10. With
some reagents, the reaction proceeded even at room temperature
or in a PdCl2 catalyzed system,[12] but the conditions shown in
Scheme 2 were generally effective.
Figure. 2 1H NMR spectra of (A) a-CD, (B) dumbbell 27, and (C) [3]rotaxane
R13 (400ꢀMHz, DMSO-d6, 298ꢀK).
Wheel Modification via Acylation Using Anhydride
Next, the acylation of [3]rotaxane wheels was studied (Scheme 3,
Table 3).[13] This acylation was selected because reaction with
excess amount of highly reactive anhydride can be performed
homogeneously in a pyridine solvent and is expected to easily
lead to complete modification of 36 hydroxyl groups on one
[3]rotaxane.
Consequently, acylation proceeded successfully to give the
corresponding products R20–R22, and the following five points
should be noted. (1) Every acylation of a-CD proceeded at around
60 °C to give the peracylated a-CD in an almost quantitative yield
(Entries 1–4). (2) With [3]rotaxanes R1 and R2, mixtures of
decomposed products were obtained with peracetylated a-CD
(Entries 5 and 6). Acetylation could accelerate deslipping
because strong intermolecular hydrogen bonds between the two
CD wheels in [3]rotaxane were lost.[11] (3) Heating was a
significant factor here. With [3]rotaxane R7, whose deslipping
reaction was restricted, acetylation at 60 °C afforded partially
acetylated products, although free a-CD was completely
acetylated under the same conditions (Entry 7).
Table 2. Chemical structures of phenylboronic acid reagents and yields of
[3]rotaxanes.
B(OH)2
OH
B(OH)2
B(OH)2
B(OH)2
B(OH)2
Reagent
CONH2
R14(77)
O
[3]rotaxane
Yield(%)
R16(88)
R15(67)
R17(88)
R13(95)
B(OH)2 B(OH)2
Reagent
NO2
Scheme 3 Acylation of [3]rotaxanes and a-CD.
O
O O
O
(excess)
(OCOR)18
[3]rotaxane
Yield(%)
R
R
R18(79) R19(76)
R1
R1
R2
R2
H H
H
H
O
O
N
N
N
N
N
N
H
N
H
N
H
R2
O
R2
O
R1
Pyridine
temp., time
R1
H
1
(ROCO)18
Native α-CD based
Figure 2 shows H NMR spectra of R13. Only the k peak of the
urea shifted from the corresponding dumbbell 27 to [3]rotaxane
R13, whereas no significant shifts were observed for other
protons. Thus, wheels were estimated to locate around urea
bonds, far away from the aldehyde groups on the axle ends.
These results indicate that the obtained [3]rotaxanes could be
further modified, and even polymerization could be initiated from
this point as experimentally confirmed.[11] This modification
methodology can expand the uses of CD-based rotaxane;
however, one drawback is its poor solubility in organic solvents.
Solubility was improved by wheel modification, which is described
in the following section.
compounds
Peracylated compounds
R1
R2
H
H
O
N
H
N
N
N
H
OH
O
R2
O
R1
Native
α-CD based
compounds
O
6
[3]rotaxane
R1 (R1= H, R2= Br)
HO
OH
R2 (R1= H, R2= OMe)
R7 (R1= Br, R2= OMe)
α-CD
(OCOR)18
Br
MeO
H
N
O
H
OMe
Br
O
N
H
OCOR
O
N
N
H
Peracylated
α-CD based
compounds
O
(ROCO)18
6
ROCO
OCOR
Peracylated[3]rotaxane
R20 (R= Me)
R21 (R= Et)
R22 (R= Pr)
Peracylatedα-CD
Table 3. Reaction conditions of acylation.
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Native
Acid
anhydride [°C]
Temp. Time
Entry
Products
α-CD based
[h]
compound
1
α-CD
Acetic
Propionic 80
Butyric 80
Isobutyric 80
60
12
Peracetylated α-CD (quant.)
2
3
α-CD
12 Perpropionylated α-CD (98%)
12 Perbutyrylated α-CD (98%)
12 Perisobutyrylated α-CD (98%)
α-CD
4
α-CD
5
[3]rotaxane R1
[3]rotaxane R2
[3]rotaxane R7
[3]rotaxane R7
[3]rotaxane R7
[3]rotaxane R7
Acetic
Acetic
Acetic
Acetic
Acetic
Acetic
60
60
60
60
80
80
12
12
decomp.
decomp.
6
7
12
Partially reacted crude
Partially reacted crude
R20 (72%)
8
168
12
9
10
2.5
12
R20 (85%)
11 [3]rotaxane R7 Propionic 80
R21 (72%)
12
13
[3]rotaxane R7
Butyric
80
12
R22 (46%)
[3]rotaxane R7 Isobutyric 80
12
Partially reacted crude
Figure. 3 1H NMR spectra of (A) peracetylated a-CD and (B) [3]rotaxane R20
(400ꢀMHz, CDCl3, 298ꢀK).
The reaction remained incomplete even after a prolonged
reaction time (one week) (Entry 8). However, reaction at 80 °C for
12ꢀh resulted in complete acetylation to give [3]rotaxane R20
(Entry 9). With [3]rotaxane, the reaction points were more
crowded owing to the existence of a dumbbell and another wheel;
thus, harsher conditions were required compared to those with a-
CD at the single molecular level. (4) Propionylation and butylation
of [3]rotaxane R7 also proceeded similarly to acetylation, but only
partial isobutylation occurred, although single a-CD could be
perisobutylated (Entries 11–13; see ESI). This was caused by
steric hindrance around the wheels in [3]rotaxane. (5) The yields
of acylated rotaxanes were less than those of single a-CD. This
was probably because the deslipping reaction of [3]rotaxane
occurred during acylation. Besides, bulky butylated rotaxane
showed a faster deslipping reaction than smaller acylated
rotaxanes.[11] In order to prevent this decrease in the acylation
yield, a shorter reaction time was considered, and 2.5ꢀh was found
to be suitable (Entry 10). The obtained peracylated rotaxanes
were soluble in various organic solvents, including CH2Cl2, CHCl3,
PhCl, and tetrahydrofuran (THF). Notably, the C–H signals of
C(1)H to C(6)H of the glucose units of CD in 1H NMR were clearly
observed for peracetylated rotaxane R20, showing its usefulness
in dynamic property analysis (Figure. 3). Besides, axle end
modified rotaxanes such as R13 could also be peracetylated.
Briefly, increasing the solubility of CD-based [3]rotaxane in
organic solvents was achieved here in a facile manner. Although
further experimental results would be needed to claim its
generality and the utility of this approach, these features are
surely important to fabricate novel rotaxane-based nanomaterials.
Conclusions
In conclusion, we determined the scope and limitations of the urea
end-capping method for synthesizing a-CD-based [3]rotaxanes
with head-to-head structure. Although it was still difficult to claim
wide generality of this method, the appropriate steric hinderance,
reactivity and the water dispersity of capping agents is definitely
important for our developed system. Besides, the successive
modification and functionalization of the axle ends and wheels of
the obtained [3]rotaxanes were also developed. Wheel acylation
made the rotaxanes highly soluble in various organic solvents,
although the further trails would be added to claim its wide
generality. The obtained rotaxanes had relatively simple
structures, consisting of two CD wheels and an alkylene axle with
bulky phenyl substituents on its edge, making them potentially
suitable as building blocks for further functional systems. These
findings expanded the synthetic flexibility of CD-based rotaxanes,
enabling further development of novel supramolecular
architectures.
Experimental section
1. General Method
1H- (400 MHz) and 13C- (100 MHz) NMR spectra were recorded
on a JEOL AL-400 spectrometer and 1H- (300 MHz) NMR spectra
were recorded on a Bruker DPX spectrometer 300 using CDCl3
and DMSO-d6 as the solvents, calibrated using residual
undeuterated solvent or tetramethylsilane as the internal standard.
IR spectra were recorded on a JASCO FT/IR-230 spectrometer.
Melting points were measured on
a
MELTING POINT
APPARATUS SMP3 (Stuart Scientific) instrument. Preparative
GPC was carried out using a HPLC LC-918 instrument by Japan
Analytical Industry with a Megapack-Gel 201C and a JAIGEL-H.
ESI HR-MS spectra were taken on a Bruker Daltonics micrOTOF
II at the Center for Advanced Material Analysis, Tokyo Institute of
Technology on request. Wako Gel® C-400HG (Wako Pure
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10.1002/ejoc.201900362
European Journal of Organic Chemistry
FULL PAPER
Chemical Industries) was used for silica gel column
chromatography. Cerite® (Wako Pure Chemical Industries) was
used for removal of metal compounds. a-Cyclodextrin (a-CD) was
dried at 70 °C overnight under reduced pressure before use. Dry
DMF was purchased from Sigma-Aldrich Company. CH2Cl2 was
purchased from Tokyo Chemical Industry Company and distilled
before using. Other commercially available reagents and solvents
were used without further purification unless otherwise noted.
[3]Rotaxane R2 (0.57 g, 64%); m.p. 274.0–275.0 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.03 (dd, 2H, J1 = 1.5 Hz,
J2 = 7.3 Hz), 7.86 (s, 2H), 6.94 (dd, 2H, J1 = 1.7 Hz, J2 = 7.9 Hz),
6.84 (m, 4H), 6.31 (br, 2H), 5.93 (s, 12H, O(3)H), 5.33 (d, 12H, J
= 6.2 Hz, O(2)H), 4.77 (s, 12H, C(1)H), 4.55 (t, 12H, J = 5.1 Hz,
O(6)H), 3.84–3.17 (m, 78H), 3.00–2.86 (m, 4H), 1.46–1.23 (m,
20H) ppm; 13C NMR (100 MHz, 298 K, DMSO-d6) δ 155.1, 147.4,
129.4, 121.0, 120.4, 118.1, 110.5, 102.4, 81.5, 73.4, 72.4, 72.1,
59.5, 55.8, 40.0, 31.5, 31.1 (4C), 30.8, 28.3 ppm; IR (KBr) u 3311,
2929, 2854, 1666, 1552, 1459, 1435, 1407, 1362, 1330, 1288,
1251, 1152, 1080, 1031, 949, 851, 754, 704, 571, 433, 411 cm–1;
2. Chemical Synthesis
Synthesis of pseudo[3]rotaxane P1 consisting of native
CDs and 1,12-Diaminododecane
a
-
–
ESI-TOF MS (m/z): calc’d for C100H161N4O64 [M–] 2442.9514;
Diaminododecane (8.8 g, 44 mmol) was added to a solution of a-
CD (86 g, 89 mmol) in H2O (600 mL), then, the mixture was
refluxed for 1 h, and stood overnight at room temperature. The
resulting mixture was filtered to collect the precipitate. It was
washed with water and dried in vacuo to give pseudo[3]rotaxane
P1 (95 g, quant.) as a white crystal. The obtained inclusion
found 2442.9505.
[3]Rotaxane R3 (0.54 g, 60%); m.p. 260.0–261.0 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.08 (s, 2H), 6.98 (s, 4H),
6.52 (s, 2H), 5.73 (s, 12H, O(3)H), 5.56 (d, 12H, J = 5.8 Hz, O(2)H),
5.27 (br, 2H), 4.78 (s, 12H, C(1)H), 4.61 (t, 12H, J = 4.9 Hz, O(6)H),
complex was immediately decomposed when dissolved in solvent. 3.87–3.18 (m, 72H, H of CD), 3.10–2.89 (m, 4H), 2.19 (s, 12H),
Therefore, the structure was assigned after further end-capping
reaction as follow.
1.56–1.20 (m, 20H) ppm; 13C NMR (100 MHz, 298 K, DMSO-d6)
δ 154.9, 140.1, 137.4, 122.8, 115.6, 102.2, 81.8, 73.5, 72.2, 72.1,
59.7, 40.3, 31.0, 30.8, 30.7, 30.6, 28.0, 21.2 ppm; IR (KBr) u 3345,
2927, 2857, 1667, 1615, 1550, 1458, 1417, 1366, 1329, 1284,
1239, 1152, 1081, 1031, 948, 844, 749, 703, 608, 575 cm–1; ESI-
Typical procedure for the synthesis of [3]rotaxanes:
synthesis of [3]rotaxane R1 consisting of native
a
-CDs and
–
o-bromophenylurea termini
TOF MS (m/z): calc’d for C102H165N4O62 [M–] 2437.9887; found
Pseudo[3]rotaxane P1 (0.81 g, 0.37 mmol) was dispersed in H2O
(5.0 mL), to the resulting mixture cooled to 0 °C was added o-
bromophenylisocyanate (0.73 g, 3.7 mmol), and the mixture was
stirred for 1 h at 0 °C. The heterogeneous mixture was poured
into THF and filtered to collect the precipitated solid. The residue
was washed with water and dried in vacuo to give the [3]rotaxane
R1 (0.69 g, 73%) as a white solid; m.p. 280.0–281.0 °C
(decomp.); 1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.03 (d, 2H, J
= 7.8 Hz, d), 7.78 (s, 2H, e), 7.54 (d, 2H, J = 7.8 Hz, a), 7.28 (t,
2H, J = 7.8 Hz, b), 6.90 (t, 2H, J = 7.8 Hz, c), 6.50 (br, 2H, f), 5.94
(s, 12H, O(3)H), 5.32 (d, 12H, J = 7.1 Hz, O(2)H), 4.77 (s, 12H,
C(1)H), 4.58 (t, 12H, J = 5.0 Hz, O(6)H), 3.81–3.17 (m, 72H, H of
CD), 3.00–2.86 (m, 4H, g), 1.43–1.25 (m, 20H, h, i, j, k and l) ppm;
13C NMR (100 MHz, 298 K, DMSO-d6) δ154.7, 137.7, 132.3,
128.0, 123.4, 121.8, 112.5, 102.4, 81.5, 73.4, 72.4, 72.2, 59.6,
2437.9860.
[3]Rotaxane R4 (0.12 g, 13%); m.p. 273.0–274.0 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 7.42 (s, 2H), 7.06–6.96
(m, 6H), 5.78 (s, 12H, O(3)H), 5.53 (s, 12H, O(2)H), 5.11 (br, 2H),
4.78 (s, 12H, C(1)H), 4.56 (s, 12H, O(6)H), 3.85–3.15 (m, 72H, H
of CD), 3.05–2.95 (m, 4H), 2.12 (s, 12H), 1.57–1.18 (m, 20H)
ppm; 13C NMR (100 MHz, 298 K, DMSO-d6) δ 155.0, 144.1, 127.3,
125.3, 120.5, 118.7, 110.5, 102.0, 81.6, 73.2, 72.1, 71.9, 59.5,
38.9, 32.3, 30.4, 29.7, 27.8, 25.5, 17.8 ppm; IR (KBr) u 3325, 2924,
2853, 1635, 1567, 1468, 1440, 1408, 1371, 1325, 1293, 1260,
1153, 1079, 1034, 948, 855, 762, 705, 575, 430 cm–1; ESI-TOF
MS (m/z): C102H165N4O62– [M–H] – 2437.9887; found 2437.9900.
[3]Rotaxane R5 (0.47 g, 50%); m.p. 329.6–331.2 °C (decomp.);
40.0, 31.4, 31.1 (4C), 30.9, 28.3 ppm; IR (KBr) u 3339, 2928, 2858, 1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.26–8.16 (m, 4H), 7.34–
1675, 1558, 1436, 1293, 1154, 1077, 1031, 572, 448, 433, 422
cm–1; MALDI-TOF MS (m/z): calc’d for C98H156Br2N4NaO62+ [M +
Na+] 2563.74; found 2563.58. Crystals of R1 suitable for X-ray
analysis were obtained by recrystallization from a solution of
7.23 (m, 4H), 7.01 (t, 2H, J = 7.9 Hz), 6.38 (br, 2H), 5.94 (s, 12H,
O(3)H), 5.33 (d, 12H, J = 6.2 Hz, O(2)H), 4.77 (s, 12H, C(1)H),
4.59 (t, 12H, J = 5.1 Hz, O(6)H), 3.86–3.17 (m, 72H, H of CD),
3.00–2.86 (m, 4H), 1.49–1.20 (m, 20H) ppm; 13C NMR (100 MHz,
298 K, DMSO-d6) δ 154.7, 136.9, 133.0, 127.6, 121.7, 121.0,
120.8 119.0, 110.5, 102.3, 81.5, 73.4, 72.4, 72.1, 59.5, 31.3, 31.2,
31.1, 30.8, 28.3, 28.1 ppm; IR (KBr) u 3350, 2928, 2859, 1675,
1609, 1554, 1486, 1454, 1408, 1363, 1315, 1296, 1252, 1218,
1153, 1080, 1033, 1006, 949, 938, 861, 758, 704, 608, 574 cm–1;
DMSO and H2O. Single crystal data of R1: C98H156Br2N4O62
・
C2H6SO・(H2O)15.5 Mw = 2899.47, colorless prism, size: 0.420 ×
0.160 × 0.030 mm, monoclinic, space group C2 (#5), Z = 4, a =
28.654(5) Å, b = 26.847(5) Å, c = 21.393(4) Å, b = 112.238(4)°, V
= 15233 (5) Å3, Dcalc = 1.264 g/cm–3, µ = 0.643 mm–1, T = 113 K,
F(000) = 6140.0; 63313 reflections measured, of which 34390
were unique (Rint = 0.0447). 383 refined parameters, final R1 =
0.1524 for reflections with I > 2s, wR = 0.1883 (all data), GOF =
1.742. Final largest diffraction peak and hole: 6.71 and –2.69 e Å3.
CCDC deposit number: 915456.
+
ESI-TOF MS (m/z): calc’d for C100H156F6N4O64Na+ [M + Na]
2574.8905; found 2574.8855.
[3]Rotaxane R6 (0.092 g, 9.6%); m.p. 309.2–311.8 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.29 (d, 2H, J = 2.2 Hz),
8.03 (s, 2H), 7.02 (dd, 2H, J1 = 2.2 Hz , J2 = 8.8 Hz), 6.90 (d, 2H,
J = 8.8 Hz), 6.35 (br, 2H), 5.92 (s, 12H, O(3)H), 5.33 (d, 12H, J =
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10.1002/ejoc.201900362
European Journal of Organic Chemistry
FULL PAPER
6.2 Hz, O(2)H), 4.78 (s, 12H, C(1)H), 4.57 (t, 12H, J = 5.1 Hz,
O(6)H), 3.86–3.16 (m, 78H, OMe, H of CD), 3.10–2.80 (m, 4H),
1.49–1.20 (m, 20H) ppm; 13C NMR (100 MHz, 298 K, DMSO-d6)
δ 154.7, 146.5, 131.1, 123.0, 119.9, 112.3, 112.2, 102.3, 81.5,
73.4, 72.4, 72.1, 59.5, 56.1, 40.0, 31.2, 31.0 (4C), 30.8, 28.2 ppm;
136.3, 136.1, 135.2, 125.4, 121.7, 121.3, 102.4, 81.4, 73.4, 72.4,
72.1, 59.5, 31.2, 31.1 (4C), 30.9, 28.3 (4C) ppm; IR (KBr) u 3358,
2927, 2859, 2064, 1683, 1583, 1558, 1501, 1456, 1433, 1362,
1341, 1262, 1152, 1079, 1032, 1006, 949, 863, 785, 747, 703,
651, 608, 575 cm–1; ESI-TOF MS (m/z): calc’d for C98H156N6O66
IR (KBr) u 3357, 2927, 2856, 1671, 1595, 1546, 1482, 1459, 1412, Na+ [M + Na+] 2495.8870; found 2495.8927.
1363, 1328, 1295, 1244, 1152, 1080, 1032, 1006, 949, 862, 749,
704, 609, 574 cm–1; ESI-TOF MS (m/z): calc’d for
C100H160Br2N4O64Na+ [M + Na] + 2623.7631; found 2623.7589.
Preparation of phenylisocyanate derivatives as end-capping
agents
Simple phenylisocyanates were widely commercially available. In
case of multiple substituted phenylisocyanates, preparations had
to be carried out as shown in Scheme S1. Isocyanates were
formed by using triphosgene with aniline derivatives and Curtius
rearrangement with benzoic acid derivatives.
[3]Rotaxane R7 (0.12 g, 12%); m.p. 315.0–318.0 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.02 (d, 2H, J = 7.0 Hz),
7.95 (s, 2H), 7.11 (d, 2H, J = 2.0 Hz), 7.01 (dd, 2H, J1 = 2.0 Hz ,
J2 = 7.0 Hz), 6.37 (br, 2H), 5.94 (s, 12H, O(3)H), 5.29 (d, 12H, J
= 6.2 Hz, O(2)H), 4.76 (s, 12H, C(1)H), 4.55 (t, 12H, J = 5.1 Hz,
O(6)H), 3.86–3.16 (m, 78H, OMe, H of CD), 3.07–2.80 (m, 4H),
1.49–1.19 (m, 20H) ppm; 13C NMR (100 MHz, 298 K, DMSO-d6)
δ 155.7, 149.1, 129.8, 123.9, 120.0, 114.5, 113.0, 103.2, 82.3,
74.3, 73.2, 73.0, 60.3, 57.1, 40.0, 32.2, 31.9 (4C), 31.7, 29.0 ppm;
Bromination of [3]rotaxane R2 via N-bromosuccinimide
N-Bromosuccinimide (0.82 g, 4.6 mmol) was added to a solution
of R2 (5.3 g, 2.1 mmol) in DMF (20 mL), the mixture was stirred
at ambient condition for 12 hours. The mixture was poured into
IR (KBr) u 3360, 2927, 2858, 1671, 1599, 1550, 1488, 1458, 1401, H2O and filtered to collect the precipitate. It was washed with
1363, 1330, 1295, 1249, 1218, 1152, 1079, 1032, 1006, 949, 862,
748, 703, 656, 608, 577 cm–1; ESI-TOF MS (m/z): calc’d for
C100H160N4O64– [M–] 2597.7682; found 2597.7639.
acetone dried in vacuo to give R7 (5.3 g, 97%) as a pale brown
solid.
Typical method for suzuki coupling reaction with [3]rotaxane
R7
[3]Rotaxane R8 (0.044 g, 4.3%); m.p. 314.1–315.9 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.53 (s, 2H), 7.72 (s, 2H),
7.70 (s, 2H), 7.42 (s, 2H), 5.74 (s, 12H, O(3)H), 5.58 (d, 12H, J =
6.2 Hz, O(2)H), 5.48 (br, 2H), 4.79 (s, 12H, C(1)H), 4.67 (t, 12H,
J = 5.1 Hz, O(6)H), 3.86–3.16 (m, 72H, H of CD), 3.10–2.80 (m,
4H), 1.58–1.24 (m, 20H) ppm; 13C NMR (100 MHz, 298 K, DMSO-
d6) δ 154.2, 143.1, 131.1, 124.6, 122.4, 119.2, 102.2, 95.3, 81.8,
73.5, 72.3, 72.1, 59.7, 40.0, 30.8 (8C), 28.0 ppm; IR (KBr) u 3375,
2926, 2858, 1677, 1576, 1534, 1438, 1401, 1363, 1329, 1299,
1265, 1229, 1152, 1079, 1032, 1005, 949, 843, 748, 704, 667,
K2CO3 aq. (0.22 g, 1.6 mmol, H2O 0.4 mL) was added to a solution
of 4-formylphenylboronic acid (0.24 g, 1.6 mmol) and [3]rotaxane
R7 (0.26 g, 0.10 mmol) in DMF (2.0 mL), then the system was
freeze degassed. Pd(PPh3)4 (12 mg, 0.010 mmol) was added to
a solution quickly, and the mixture was stirred for 17 hours at
80 °C. The heterogeneous mixture was poured into H2O and
filtered to collect the precipitate. It was washed with water and
acetone dried in vacuo to give the [3]rotaxane R13 (0.25 g, 95%)
1
as a gray solid; m.p. 315.5–317.6 °C (decomp.); H NMR (300
607,
576
cm–1;
ESI-TOF
MS
(m/z):
calc’d
for
MHz, 298 K, DMSO-d6) δ 10.03 (s, 2H), 8.22 (d, 2H, J = 8.7 Hz),
8.07 (br, 2H), 7.99–7.90 (m, 8H), 7.37–7.29 (m, 4H), 6.44 (br, 2H),
5.95 (s, 12H, O(3)H), 5.31 (s, 12H, O(2)H), 4.78 (s, 12H, C(1)H),
4.57 (s, 12H, O(6)H), 3.96 (s, 6H, OMe), 3.86–3.16 (m, 72H, H of
CD), 3.07–2.80 (m, 4H), 1.49–1.19 (m, 20H) ppm; 13C NMR (100
MHz, 298 K, DMSO6) δ 192.7, 154.9, 147.8, 146.0, 134.5, 131.1,
130.3, 130.1 (4C), 126.7 (4C), 119.6, 118.0, 109.1, 102.3, 81.5,
73.4, 72.4, 72.1, 67.0, 59.5, 56.0, 41.1, 31.4, 31.0 (4C), 30.8, 28.2
ppm; IR (KBr) u 3360, 2928, 2859, 1680, 1597, 1566, 1536, 1508,
1487, 1462, 1405, 1364, 1333, 1296, 1237, 1215, 1153, 1080,
1033, 1006, 948, 820, 750, 704, 651, 609, 573 cm–1; ESI-TOF MS
(m/z): calc’d for C114H170N4O66– [M–] 2649.9996; found 2649.9937.
C98H154Br2I2N4O62Na+ [M + Na+] 2814.5402; found 2814.5352.
[3]Rotaxane R9 (0.15 g, 16%); m.p. 305.0–308.0 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.56 (s, 2H), 7.76 (s, 2H),
7.40 (s, 2H), 7.17 (s, 2H), 5.74 (s, 12H, O(3)H), 5.56 (d, 12H, J =
6.2 Hz, O(2)H), 5.47 (br, 2H), 4.78 (s, 12H, C(1)H), 4.67 (t, 12H,
J = 5.1 Hz, O(6)H), 4.29 (s, 2H), 3.86–3.16 (m, 72H, H of CD),
3.10–2.80 (m, 4H), 1.58–1.20 (m, 20H) ppm; 13C NMR (100 MHz,
298 K, DMSO-d6) δ 154.8, 142.6, 126.7, 124.3, 122.1, 121.0,
119.7, 102.6, 82.6, 82.3, 82.2, 73.9, 72.7, 72.5, 60.1, 31.3 (8C),
31.2, 28.4 ppm; IR (KBr) u 3360, 2927, 2857, 1671, 1599, 1575,
1542, 1438, 1410, 1363, 1328, 1294, 1229, 1152, 1080, 1033,
949, 853, 747, 703, 666, 610, 573 cm–1; ESI-TOF MS (m/z): calc’d
for C102H156Br2N4O62Na+ [M + Na+] 2610.7470; found 2610.7380.
R14 (0.21 g, 77%); 1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.18
(d, J = 8.3 Hz, 2H), 8.14–8.09 (m, 2H), 8.00 (br, 2H), 7.84–7.77
(m, 4H), 7.51 (dd, J1 = J2 = 7.5 Hz, 2H), 7.44 (s, 2H), 7.28 (s, 2H),
7.24 (d, J = 8.3 Hz, 2H), 6.39 (br, 2H), 5.94 (s, 12H, O(3)H), 5.34
(d, J = 5.0 Hz, 12H, O(2)H), 4.78 (s, 12H, C(1)H), 4.58 (s, 12H,
O(6)H), 3.95 (s, 6H, OMe), 3.86–3.15 (m, 72H, H of CD), 3.02–
2.87 (m, 4H), 1.49–1.19 (m, 20H) ppm; 13C NMR (100 MHz, 298
K, DMSO6) δ 168.4, 155.4, 148.2, 140.7, 135.3, 132.7, 129.8,
129.5, 129.3, 126.5, 125.5, 119.4, 118.6, 109.4, 102.8, 82.0, 73.8,
[3]Rotaxane R10 (0.19 g, 21%); m.p. 311.5–313.6 °C (decomp.);
1H NMR (400 MHz, 298 K, DMSO-d6) δ 9.34 (s, 2H), 8.39 (d, 2H,
J = 8.6 Hz), 8.09 (dd, 2H, J1 = 8.2 Hz, J2 = 1.4 Hz), 7.65 (t, 2H, J
= 8.2 Hz), 7.18–7.05 (m, 4H), 5.98 (s, 12H, O(3)H), 5.26 (d, 12H,
J = 6.2 Hz, O(2)H), 4.77 (s, 12H, C(1)H), 4.53 (t, 12H, J = 5.1 Hz,
O(6)H), 3.87–3.16 (m, 72H, H of CD), 3.03–2.85 (m, 4H), 1.51–
1.21 (m, 20H) ppm; 13C NMR (100 MHz, 298 K, DMSO-d6) δ 154.0, 72.8, 72.6, 60.0, 56.5, 31.9, 31.6 (6C), 31.3, 28.8 ppm; ESI-TOF
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10.1002/ejoc.201900362
European Journal of Organic Chemistry
FULL PAPER
2+
MS (m/z): calc’d for C114H172N6O66 [M2+] 1364.0052; found
1364.0068.
R19 (0.21 g, 76%); m.p. 309.7–311.5 °C (decomp.);1H NMR (400
MHz, 298 K, DMSO-d6) δ 8.44 (dd, J1 = J2 = 1.9 Hz, 2H), 8.22 (d,
J = 8.2 Hz, 2H), 8.16 (dd, J1 = 8.2 Hz, J2 = 1.9 Hz, 2H), 8.07 (br,
2H), 7.72 (dd, J1 = J2 = 8.2 Hz, 2H), 7.35 (d, J = 1.7 Hz, 2H), 7.29
(dd, J1 = 8.2 Hz, J2 = 1.7 Hz, 2H), 6.41 (br, 2H), 5.98 (s, 12H,
R15 (0.18 g, 67%); 1H NMR (400 MHz, 298 K, DMSO-d6) δ 8.09
(d, J = 8.3 Hz, 2H), 7.93 (br, 2H), 7.25 (s, 4H), 7.16 (s, 2H), 7.11
(d, J = 8.3 Hz, 2H), 6.92 (s, 2H), 6.34 (br, 2H), 5.93 (s, 12H, O(3)H), O(3)H), 5.28 (d, J = 7.2 Hz, 12H, O(2)H), 4.78 (s, 12H, C(1)H),
5.33 (d, J = 5.0 Hz, 12H, O(2)H), 4.76 (s, 12H, C(1)H), 4.56 (s,
12H, O(6)H), 3.91 (s, 6H, OMe), 3.85–3.11 (m, 72H, H of CD),
3.01–2.83 (m, 4H), 2.31 (s, 12H), 1.47–1.19 (m, 20H) ppm; 13C
NMR (100 MHz, 298 K, DMSO6) δ 155.5, 148.1, 140.6, 138.1,
133.6, 132.0, 129.3, 129.2, 128.6, 124.6, 119.1, 118.6, 109.2,
102.8, 82.0, 73.8, 72.8, 72.6, 60.0, 56.4, 31.9, 31.5 (6C), 31.3,
28.7, 21.5 (12C) ppm; ESI-TOF MS (m/z): calc’d for
C116H178N4O64Na+ [M + Na +] 2674.0689; found 2674.0665.
4.61 (s, J = 5.2 Hz, 12H, O(6)H), 3.96 (s, 6H, OMe), 3.88–3.14 (m,
72H, H of CD), 3.02–2.83 (m, 4H), 1.49–1.19 (m, 20H) ppm; 13
C
NMR (100 MHz, 298 K, DMSO6) δ155.3, 148.9, 148.3, 142.4,
133.3, 130.8, 130.6 (4C), 121.8, 121.0, 119.7, 118.5, 109.6, 102.8,
82.0, 73.8, 72.8, 72.5, 59.9, 56.5, 31.9, 31.6 (6C), 31.3, 28.7 ppm;
IR (KBr) u 3367, 2927, 2859, 2144, 1673, 1599, 1524, 1459, 1406,
1351, 1266, 1237, 1213, 1152, 1079, 1032, 1005, 949, 937, 902,
857, 806, 744, 704, 649, 608, 574 cm–1; ESI-TOF MS (m/z): calc’d
for C112H168N6O682+ [M2+] 1365.9845; found 1365.9864.
R16 (0.25 g, 88%); m.p. 295.4–297.0 °C (decomp.);1H NMR (400
MHz, 298 K, DMSO-d6) δ 8.37–8.03 (m, 22H), 7.20 (s, 2H), 7.12
(d, J = 8.7 Hz, 2H), 6.45 (br, 2H), 5.97 (s, 12H, O(3)H), 5.32 (d, J
= 5.0 Hz, 12H, O(2)H), 4.79 (s, 12H, C(1)H), 4.60 (s, 12H, O(6)H),
3.92 (s, 6H, OMe), 3.87–3.16 (m, 72H, H of CD), 3.05–2.88 (m,
4H), 1.49–1.18 (m, 20H) ppm; 13C NMR (100 MHz, 298 K,
DMSO6) δ155.6, 147.9, 138.0, 137.2, 131.5, 130.9, 130.3, 129.3,
Synthesis of [3]rotaxane R20
Ac2O (0.50 mL, 0.50 g, 5.0 mmol) was added to a solution of
[3]rotaxane R7 (0.10 g, 0.040 mmol) in pyridine (0.50 mL),then
the mixture was stirred at 80 °C for 2.5 hours. The mixture was
poured into H2O and filtered to collect the precipitate. It was
washed with water, dried in vacuo to give the [3]rotaxane R20
1
128.6, 128.3, 128.2, 128.0, 127.9, 126.8, 125.8, 125.5 (4C), 125.3, (0.14 g, 85%) as a pale yellow solid; H NMR (300 MHz, 298 K,
124.7, 124.6, 123.0, 114.1, 113.0, 102.8, 82.0, 73.8, 72.8, 72.6,
60.0, 56.4, 32.0, 31.6 (8C), 31.3 ppm; IR (KBr) u 3364, 2928,
2858, 1654, 1595, 1543, 1507, 1488, 1458, 1435, 1406, 1363,
1328, 1295, 1243, 1152, 1079, 1035, 1006, 948, 902, 851, 751,
723, 702, 655, 609, 575 cm–1 ESI-TOF MS (m/z): calc’d for
C132H178N4O642+ [M2+] 1445.0307; found 1445.0338.
CDCl3) δ 8.33 (d, J = 8.8 Hz, 2H), 7.25 (dd, J1 = 8.8 Hz, J2 = 2.0
Hz, 2H), 7.02 (d, J = 2.0 Hz, 2H), 6.63 (br, 2H), 5.79 (br, 2H), 5.36
(t, J = 8.5 Hz, 12H, C(3)H), 5.03 (d, J = 3.4 Hz, 12H, C(1)H), 4.87
(dd, J1 = 8.5 Hz, J2 = 3.4 Hz, 12H, C(2)H), 4.45–4.21 (m, 36H,
C(6)Ha, C(6)Hb, C(5)H), 3.96 (s, 6H, OMe), 3.90 (t, J = 8.5 Hz,
12H, C(4)H), 3.76–3.31 (m, 4H, NH–CH2–), 2.13 (s, 36H, Ac),
2.07 (s, 36H, Ac), 2.01 (s, 36H, Ac), 1.70-1.18 (m, 20H,
methylene) ppm; 13C NMR (100 MHz, 298 K, CDCl3) δ 170.6,
170.3, 169.0, 154.4, 147.0, 127.3, 124.7, 119.1, 114.5, 113.6,
98.6, 78.4, 71.3, 70.7, 70.5, 62.1, 56.0, 41.1, 32.1, 31.5, 31.0,
29.8, 27.3, 21.0, 20.8, 20.7 ppm; ESI-TOF MS (m/z): calc’d for
C172H232N4O100Br22+ [M2+] 2080.5693; found 2080.5725.
R17 (0.23 g, 88%); 1H NMR (400 MHz, 298 K, DMSO-d6) δ 9.41
(br, 2H), 8.11 (d, J = 7.6 Hz, 2H), 7.93 (br, 2H), 7.20 (dd, J1 = J2
= 7.6 Hz, 2H), 7.13 (d, J = 1.7 Hz, 2H), 7.11–7.04 (m, 4H), 7.00
(dd, J1 = J2 = 1.7 Hz, 2H), 6.70 (dd, J1 = 7.6 Hz, J2 = 1.7 Hz, 2H),
6.35 (br, 2H), 5.92 (s, 12H, O(3)H), 5.29 (d, J = 6.3 Hz, 12H,
O(2)H), 4.76 (s, 12H, C(1)H), 4.54 (t, J = 5.6 Hz, 12H, O(6)H),
3.90 (s, 6H, OMe), 3.85–3.14 (m, 72H, H of CD), 3.00–2.86 (m,
4H), 1.49–1.19 (m, 20H) ppm; 13C NMR (100 MHz, 298 K,
DMSO6) δ158.2, 155.4, 148.1, 142.2, 133.6, 130.2 (4C), 119.0,
118.5, 117.6, 114.2, 113.5, 109.2, 102.8, 82.0, 73.8, 72.8, 72.5,
59.9, 56.3, 31.9, 31.5 (6C), 31.3, 28.7 ppm; ESI-TOF MS (m/z):
calc’d for C112H170N4O662+ [M2+] 1336.9944; found 1336.9970.
Synthesis of [3]rotaxane R21
Propionyl anhydride (1.0 mL, 1.0 g, 7.7 mmol) was added to a
solution of [3]rotaxane R7 (0.10 g, 0.040 mmol) in pyridine (1.0
mL), then the mixture was stirred at 80 °C for 12 hours. The
mixture was poured into H2O and filtered to collect the precipitate.
It was washed with water, purified by preparative GPC (eluent;
CHCl3) to give the [3]rotaxane R21 (0.13 g, 72%) as a pale yellow
solid; m.p. 155.8–156.9 °C; 1H NMR (300 MHz, 298 K, CDCl3) δ
8.36 (d, J = 8.8 Hz, 2H), 7.31–7.21 (m, 2H), 7.03 (d, J = 2.0 Hz,
2H), 6.69 (br, 2H), 5.89 (br, 2H), 5.38 (t, J = 8.5 Hz, 12H, C(3)H),
5.01 (d, J = 3.4 Hz, 12H, C(1)H), 4.84 (dd, J1 = 8.5 Hz, J2 = 3.4
Hz, 12H, C(2)H), 4.41–4.24 (m, 36H, C(6)Ha, C(6)Hb, C(5)H), 3.97
(s, 6H, OMe), 3.86 (t, J = 8.5 Hz, 12H, C(4)H), 3.74–3.29 (m, 4H,
NH–CH2–), 2.50–2.14 (m, 72H, OCO–CH2–), 1.70-1.19 (m, 20H,
methylene), 1.18–1.00 (m, 108H, OCOCH2–CH3) ppm; IR (KBr) u
3413, 2981, 2944, 2884, 1747, 1689, 1595, 1525, 1464, 1421,
1382, 1352, 1275, 1177, 1087, 1045, 1021, 952, 884, 860, 807,
R18 (0.21 g, 79%); m.p. 278.3–280.2 °C (decomp.);1H NMR (400
MHz, 298 K, DMSO-d6) δ 10.10 (s, 2H), 8.23–8.18 (m, 4H), 8.06–
8.00 (m, 4H), 7.84 (d, J = 8.0 Hz, 2H), 7.66 (dd, J1 = J2 = 7.5 Hz,
2H), 7.32 (d, J = 1.7 Hz, 2H), 7.26 (dd, J1 = 8.0 Hz, J2 = 1.7 Hz,
2H), 6.41 (br, 2H), 5.95 (s, 12H, O(3)H), 5.32 (d, J = 6.2 Hz, 12H,
O(2)H), 4.78 (s, 12H, C(1)H), 4.57 (s, J = 5.4 Hz, 12H, O(6)H),
3.96 (s, 6H, OMe), 3.87–3.11 (m, 72H, H of CD), 3.02–2.87 (m,
4H), 1.49–1.19 (m, 20H) ppm; 13C NMR (100 MHz, 298 K,
DMSO6) δ 193.8, 155.4, 148.2, 141.5, 137.3, 132.7, 131.9, 130.2,
130.1, 128.2, 127.6, 119.4, 118.6, 109.4, 102.8, 82.0, 73.8, 72.8,
72.6, 59.9, 56.5, 31.9, 31.6 (6C), 31.3, 28.7 ppm; ESI-TOF MS
(m/z): calc’d for C114H170N4O66+ [M+] 2673.9961; found 2673.9882.
3+
765, 584 cm–1; ESI-TOF MS (m/z): calc’d for C208H304N4O100Br2
[M3+] 1562.5629; found 1562.5622.
Synthesis of [3]rotaxane R22
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10.1002/ejoc.201900362
European Journal of Organic Chemistry
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Butyric anhydride (1.0 mL, 0.97 g, 6.1 mmol) was added to a
solution of [3]rotaxane R7 (0.10 g, 0.040 mmol) in pyridine (1.0
mL), then the mixture was stirred at 80 °C for 12 hours. The
mixture was poured into H2O and filtered to collect the precipitate.
The residue was washed with water, purified by preparative GPC
(eluent; CHCl3) to give the [3]rotaxane R22 (95 mg, 46%) as a
1
pale yellow solid; m.p. 105.0–106.0 °C; H NMR (300 MHz, 298
K, CDCl3) δ 8.28 (d, J = 8.8 Hz, 2H), 7.31–7.21 (m, 2H), 7.04 (d,
J = 2.0 Hz, 2H), 6.79 (br, 2H), 5.81 (br, 2H), 5.36 (t, J = 8.5 Hz,
12H, C(3)H), 4.99 (d, J = 3.4 Hz, 12H, C(1)H), 4.84 (dd, J1 = 3.4
Hz, J2 = 8.5 Hz, 12H, C(2)H), 4.46–4.14 (m, 36H, C(6)Ha, C(6)Hb,
C(5)H), 3.98 (s, 6H, OMe), 3.87 (t, J = 8.5 Hz, 12H, C(4)H), 3.79–
3.32 (m, 4H, NH–CH2–), 2.49–2.09 (m, 72H, OCO–CH2–), 1.78–
0.83 (m, 200H, OCOCH2–CH2–, OCOCH2CH2–CH3, methylene of
axle) ppm; IR (KBr) u 3553, 3415, 2966, 2936, 2877, 1747, 1689,
1594, 1523, 1466, 1416, 1384, 1366, 1306, 1250, 1175, 1104,
1042, 1010, 963, 924, 861, 814, 751, 584 cm–1; ESI-TOF MS
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This work was supported by JST CREST Grant Number
JPMJCR1522, Japan, and JSPS KAKENHI Grant Number
JP16K17955, JP19K15620, and Eno Science Promotion
Foundation (Y. A.). Fellowship to Y. A. from JSPS for Young
Japanese Scientist is also gratefully acknowledgment.
Keywords: Cyclodextrins • Rotaxanes • Alkylchain •
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A part of this work has already been reported in the reference 7c and 9.
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FULL PAPER: Rotaxane Synthesis
Yosuke Akae, Hiromitsu Sogawa,
Toshikazu Takata*
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Effective Synthesis and Modification
a
of -Cyclodextrin-Based
[3]Rotaxanes Enabling Versatile
Molecular Design
Facile synthesis of a-cyclodextrin-(a-CD-) based [3]rotaxanes and their structural
modifications are discussed in detail. Pseudo[3]rotaxane was prepared from a-CD
and a,w-diaminododecane in water, successive urea-forming end-capping reactions
with isocyanate afforded [3]rotaxane. Significant modifications of the axle end and
wheel OH group of the [3]rotaxanes were performed by the Suzuki coupling with
arylboronic acids and by the perfect acylation with acid anhydrides, respectively.
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