One-pot synthesis of permethylated α-CD-based rotaxanes having alkylene chain axles and their structural characteristics

Article abstract of DOI:10.1246/cl.2012.806

Permethylated i-CD-based rotaxanes with short alkylene chains as an axle were synthesized through urea end-capping in one pot: Products were [2]rotaxane and [3]rotaxane. The headto-head structure of [3]rotaxane obtained as a single isomer was confirmed by the characteristic 1HNMR peak shifts and X-ray single-crystal structure analysis.

Full text of DOI:10.1246/cl.2012.806

doi:10.1246/cl.2012.806
806
Published on the web July 28, 2012
One-pot Synthesis of Permethylated ¡-CD-based Rotaxanes Having Alkylene Chain Axles
and Their Structural Characteristics
Yosuke Akae,1 Takayuki Arai,1,2 Yasuhito Koyama,1 Hisashi Okamura,1 Kohei Johmoto,3
Hidehiro Uekusa,3 Shigeki Kuwata,4 and Toshikazu Takata*1
1Department of Organic and Polymeric Materials, Tokyo Institute of Technology,
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552
2Research Laboratory, LINTEC Corporation,
5-14-42 Nishiki-cho, Warabi, Saitama 335-0005
3Department of Chemistry and Materials Science, Tokyo Institute of Technology,
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551
4Department of Applied Chemistry, Tokyo Institute of Technology,
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552
(Received May 21, 2012; CL-120436; E-mail: ttakata@polymer.titech.ac.jp)
Permethylated ¡-CD-based rotaxanes with short alkylene
chains as an axle were synthesized through urea end-capping in
one pot: Products were [2]rotaxane and [3]rotaxane. The head-
to-head structure of [3]rotaxane obtained as a single isomer was
1
confirmed by the characteristic H NMR peak shifts and X-ray
single-crystal structure analysis.
Scheme 1. One-pot synthesis of rotaxanes.
Since the discovery of cyclodextrin (CD)-containing poly-
rotaxane by Harada et al.,1-3 many attractive concepts and
materials based on their unique structures and functions have
been hitherto reported, e.g., stimuli-responsive systems,4 insu-
lated molecular wires,5 and polyrotaxane networks.6 Miyake
et al. have reported that about 80% ¡-CD in polyrotaxane takes
a head-to-head conformation to face the secondary hydroxy
groups of two CDs, as determined by STM measurements.7 In
addition, several reports including the X-ray crystal structure
analysis of the inclusion complex of CD also support the
probability of the favorable head-to-head formation.8 The
selective head-to-head formation strongly suggests the important
contribution of “intermolecular” hydrogen-bondings between
two CDs. The coupled CDs seem to act as one fragment during
a threading process of polyrotaxane synthesis. The directional
regularity of CDs on the polyrotaxane could affect densely to the
polyrotaxane-specific sliding properties, because the dynamic
behavior of each CD would be related to the interactions with
the adjacent CDs. On the other hand, O-methylated ¡-CD
derivatives such as permethylated ¡-CD (PMeCD) are frequent-
ly used to overcome the low solubility of the corresponding
polyrotaxanes consisting of native ¡-CDs in organic solvents
and to restrict the reacting points on the ¡-CD. However, the
directional regularity of PMeCDs has not been unveiled yet, due
to the synthetic challenges of the PMeCD-based simple model
rotaxane to clarify the regularity. We have recently disclosed the
one-pot high-yielding synthesis of ¡-CD-based polyrotaxane9
and a simple alkylene axle-containing rotaxane10 in water. We
expected that this synthetic protocol would be applicable to the
PMeCD-based simple rotaxane consisting of very weak inter-
actions between the components.
Table 1. Synthesis of rotaxanes consisting of PMeCD via urea
end-capping in watera
Entry
1
n of (CH2)n
Product
Yieldb/%
10
[3]rotaxane 1
[2]rotaxane 2
[3]rotaxane 3
[2]rotaxane 4
[3]rotaxane 5
[2]rotaxane 6
trace
trace
8
2
3
12
18
15
16
trace
a200 mol % of PMeCD per ¡,½-diaminoalkane was used.
bIsolated yield.
analyses of the resulting [3]rotaxanes first revealed the un-
expected characteristics of PMeCD to afford selectively a head-
to-head conformation, the same as ¡-CD-based [3]rotaxane.8
Scheme 1 shows the synthesis of PMeCD-based simple
rotaxanes using several ¡,½-diaminoalkanes as the axle compo-
nent. The results are summarized in Table 1. The threading
reaction of the axle into PMeCD was carried out in water at 0 °C
on the basis of the lower critical solution temperature (LCST) of
PMeCD in water. After stirring for 1 h, to the mixture was
directly added 3,5-dimethylphenyl isocyanate as an end-capping
agent. Standard workup gave corresponding rotaxanes. As a
result, the use of 1,10-diaminodecane afforded a trace amount
of [3]rotaxane 1 and [2]rotaxane 2 (Entry 1), which were
detectable by the MALDI-TOFMS. Surprisingly, a combina-
tion of 1,12-diaminododecane with PMeCD yielded a single
[3]rotaxane isomer 3 (8%) along with [2]rotaxane 4 (15%,
Entry 2). Moreover, a combination of PMeCD with 1,18-
diaminooctadecane also afforded the corresponding [3]rotaxane
5 in 16% yield as a single isomer together with a trace amount of
Herein, we describe the synthesis of simple rotaxanes
consisting of PMeCD as a wheel and a short alkylene chain as
an axle component by urea end-capping in one pot and the
structural characterization of the rotaxanes.7 The structural
Chem. Lett. 2012, 41, 806-808
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

807
Figure 1. 1H NMR spectra of (A) PMeCD, (B) 4, (C) 3, and (D) 5 (400 MHz, CDCl3, 298 K).
Figure 3. Proposed structure of [2]rotaxane 4 by NOESY
correlation.
to-head conformation, whereas the competitive formation of
[2]rotaxane is characteristic of PMeCD, but not of native ¡-
CD.10 The axle moiety is disordered and presented as a vague
rod-like electron density distribution in Figure 2, which was not
modeled. The electron densities outside of the CD units would
be due to the crystalline solvents. The disorder of the axle
moiety is probably due to the delocalization of the axle
component originating from the shuttling and/or rotational
movement that blurred the electron density. However, the
electron density distribution of the axle moiety supports
certainly the included structure into the cavity of PMeCD.
Meanwhile, we noticed that the peak shifts of PMeCD
signals of [2]rotaxane 4 were very similar to those of 3
(Figure 1B), indicating the similar chemical environment of
PMeCD on 4 to 3. The NOESY spectrum of 4 suggested the
abnormal inclusion complex structure, in which the tail face of
PMeCD covered the end-cap group, by the distinct NOE
correlation between the methyl groups on the end-cap groups
and the methoxy groups at the 6 position of PMeCD (Figure 3).
The proposed inclusion complex with the tail face can be more
Figure 2. X-ray crystal structure of 3.
[2]rotaxane 6. The evidence for the formation of single
[3]rotaxane isomers 3 and 5 was obtained from the H NMR
1
peak shifts based on the conversion of PMeCD to [3]rotaxane.
In the 1H NMR spectrum of 3 (Figure 1C), the signals of the
two end-cap moieties appear as one set of the peaks to suggest
either the head-to-head or the tail-to-tail conformation. The peak
shifts based on the conversion of PMeCD to 3 originate from the
shielding effects of the benzene moieties of the end-cap groups,
which perfectly coincide with that of another reported CD-based
[3]rotaxane with a head-to-head structure,10 implying the
PMeCD-directions of 3 with a head-to-head structure. Finally,
the structure of 3 was determined by X-ray single-crystal
structure analysis (Figure 2).
Figure 2 reveals that the coupled PMeCD took unambigu-
ously a head-to-head structure.11 It is very interesting that
hydroxy group-free PMeCDs are regularly arranged to the head-
Chem. Lett. 2012, 41, 806-808
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

808
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stable than that with the head face, contrary to the inclusion
behavior of native ¡-CD. Although the reason is not clear at
present time, the complex formation probably comes from the
flexible structure of PMeCD without any intramolecular hydro-
gen bonding that restricts the structure of ¡-CD. The methyl
signal (b1) included into the cavity of PMeCD on 4 (Figure 1B)
is determined by HMQC and HMBC NMR spectra of 412 and
the chemical shift of b1 is consistent with the peak (b) of 3
(Figure 1C). Therefore, it turned out that the chemical shift of b1
is diagnostic to judge the inclusion structure with the tail face.
Moreover, it was revealed that the structure of 5 took also a
head-to-head structure, which was determined by the character-
4
1
istic H NMR: (i) the simple spectrum based on the symmetric
structure, (ii) the same peak shifts as 3, and (iii) the same
chemical shift of b as b1 (Figure 1D). One of the plausible
reasons for selectively taking a head-to-head conformation of
[3]rotaxanes can be attributed to the nature of the tail face
of PMeCD that favorably forms hydrogen bondings with the
amine-termini to stabilize the inclusion structure of the
pseudorotaxane intermediate.
In conclusion, the present study has provided several crucial
insights and scientific bases for PMeCD-based rotaxane and
polyrotaxane studies by the following: (i) complete structural
characterization to elucidate the head-to-head regularity of
PMeCD-type [3]rotaxanes; (ii) the first synthesis of simple [2]-
and [3]rotaxanes consisting of PMeCD and short alkylene axles;
and (iii) the evaluation of abnormal inclusion structure of
PMeCD with the tail face in [2]rotaxane.
5
This work was financially supported by a Grant-in-Aid for
Scientific Research from Ministry of Education, Culture, Sports,
Science and Technology, Japan (No. 23245031).
6
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11 Crystallographic data of 3: C138H238N4O62, Mr = 2945.32, I4122
(#98), a = 17.9461(3) ¡, c = 55.1640(10) ¡, V = 17766.3(5) ¡3,
Z = 4, Dcalcd = 1.101 Mg m¹3, All 8154 unique reflections (Rint
=
0.0417) were used for refinement, Final R indices R1 = 0.0765
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12 Supporting Information is also available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/index.
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3
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Chem. Lett. 2012, 41, 806-808
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/