Neutralization of a sec-ammonium group unusually stabilized by the "rotaxane Effect": Synthesis, structure, and dynamic nature of a "free" sec-amine/crown ether-type rotaxane

Article abstract of DOI:10.1002/chem.201000968

A fifteen-year riddle has been settled: neutralization, the most popular chemical event, of a crown ether/sec-ammonium salt-type rotaxane has been achieved and a completely nonionic crown ether/sec-amine-type rotaxane isolated. A [2]rotaxane was prepared as a typical substrate from a mixture of dibenzo[24]crown-8 ether (DB24C8) and sec-ammonium hexafluorophosphate (PF ₆) with a terminal hydroxy group through end-capping with 3,5-dimethylbenzoic anhydride in the presence of tributylphosphane as a catalyst in 90 % yield. A couple of approaches to the neutralization of the ammonium rotaxane were investigated to isolate the free sec-amine-type rotaxane by decreasing the degree of thermodynamic and kinetic stabilities. One approach was the counteranion-exchange method in which the soft counterion PF ₆^- was replaced with the fluoride anion by mixing with tetrabutylammonium fluoride, thus decreasing the cationic character of the ammonium moiety. Subsequent simple washing with a base allowed us to isolate the free sec-amine-type rotaxane in a quantitative yield. The other approach was a synthesis based on a protection/deprotection protocol. The acylation of the sec-ammonium moiety with 2,2,2-trichloroethyl chloroformate gave an N-carbamated rotaxane that could be deprotected by treating with zinc in acetic acid to afford the corresponding free sec-amine-type rotaxane in a quantitative yield. The structure of the free sec-amine-type rotaxane was fully confirmed by spectral and analytical data. The generality of the counteranion-exchange method was also confirmed through the neutralization of a bisammonium-type [3]rotaxane. The mechanism was studied from the proposed potential-energy diagram of the rotaxanes with special emphasis on the role of the PF ₆^- counterion. Neutral and free: The neutralization of the ammonium group of crown ether/sec-ammonium salt-type rotaxanes is a simple, yet important issue, which had not been solved to date. Neutral rotaxanes had not been isolated because of their unusual stability; however, the successful synthesis of free amine-type rotaxanes has now been achieved. The key to canceling this strong stabilization is the construction of a multiple equilibrium system and the successful removal of the conjugate acid from the reaction system (see scheme). Copyright

Full text of DOI:10.1002/chem.201000968

FULL PAPER
DOI: 10.1002/chem.201000968
Neutralization of a sec-Ammonium Group Unusually Stabilized by the
“Rotaxane Effect”: Synthesis, Structure, and Dynamic Nature of a “Free”
sec-Amine/Crown Ether-Type Rotaxane
Kazuko Nakazono and Toshikazu Takata*[a]
Abstract:
A
fifteen-year riddle has
taxane by decreasing the degree of
thermodynamic and kinetic stabilities.
One approach was the counteranion-
exchange method in which the soft
protection protocol. The acylation of
the sec-ammonium moiety with 2,2,2-
trichloroethyl chloroformate gave an
N-carbamated rotaxane that could be
deprotected by treating with zinc in
acetic acid to afford the corresponding
free sec-amine-type rotaxane in a quan-
titative yield. The structure of the free
sec-amine-type rotaxane was fully con-
firmed by spectral and analytical data.
The generality of the counteranion-ex-
change method was also confirmed
through the neutralization of a bisam-
monium-type [3]rotaxane. The mecha-
nism was studied from the proposed
potential-energy diagram of the rotax-
anes with special emphasis on the role
been settled: neutralization, the most
popular chemical event, of a crown
ether/sec-ammonium salt-type rotaxane
has been achieved and a completely
nonionic crown ether/sec-amine-type
rotaxane isolated. A [2]rotaxane was
prepared as a typical substrate from a
mixture of dibenzo[24]crown-8 ether
(DB24C8) and sec-ammonium hexa-
fluorophosphate (PF6) with a terminal
hydroxy group through end-capping
with 3,5-dimethylbenzoic anhydride in
the presence of tributylphosphane as a
catalyst in 90% yield. A couple of ap-
proaches to the neutralization of the
ammonium rotaxane were investigated
to isolate the free sec-amine-type ro-
À
counterion PF6 was replaced with the
fluoride anion by mixing with tetrabu-
tylammonium fluoride, thus decreasing
the cationic character of the ammoni-
um moiety. Subsequent simple washing
with a base allowed us to isolate the
free sec-amine-type rotaxane in a quan-
titative yield. The other approach was
a synthesis based on a protection/de-
Keywords: crown compounds · ki-
netics · neutralization · rotaxanes ·
supramolecular chemistry
À
of the PF6 counterion.
Introduction
comes part of a rotaxane, the rotaxane no longer affords the
corresponding neutralized sec-amine-type rotaxane by treat-
ment with any base.[1] The large stabilization is a common
effect in various rotaxane architectures.[2–4] However, the
strong resistance of such rotaxanes to neutralization has
long been troublesome, thus preventing the application of
rotaxanes to functional devices and materials. Although low
solubility due to their ionic structure makes the formation
of higher-order rotaxanes difficult, strong intramolecular in-
teractions effectively limit the circumrotational and transla-
tional mobility of their components, which are the most
characteristic feature of the rotaxane structure. This prob-
lem is the largest to be solved in the study of crown ether-
based rotaxanes, which are the most easily accessible rotax-
anes.[5] Therefore, many scientists have long been eager to
synthesize sec-amine-type nonionic rotaxanes from sec-am-
monium salt-type rotaxanes, which are the most easily acces-
sible. The unprecedented large stabilization of the sec-am-
monium moiety when it is used as the axle component of
the rotaxane structure might be called the rotaxane effect.
Neutralization is a very popular chemical event that occurs
very quickly between an acid and a base. An ammonium
salt, a complex derived from a pair that consists of a strong
acid and an amine base, usually acts as a weak acid and is
quickly neutralized with a base stronger than its conjugate
base. However, it is possible to have an ammonium salt that
is never converted into its neutralized form: sec-ammonium
moieties that are placed in the cavities of crown ethers (es-
pecially 24-membered species; see 1·PF6; Scheme 1). It is
well known that once such a sec-ammonium moiety be-
[a] K. Nakazono, Prof. T. Takata
Department of Organic and Polymeric Materials
Tokyo Institute of Technology, Ookayama 2-12-1
Meguro-ku, Tokyo 152-8552 (Japan)
Fax : (+81)3-5734-2888
E-mail: takata.t.ab@m.titech.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201000968.
Chem. Eur. J. 2010, 16, 13783 – 13794
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13783

In addition, we had already
determined the kinetic acidity
of
a sec-ammonium salt-type
rotaxane by means of an H/D
exchange experiment.[1] The
acidity of the ammonium salt-
type rotaxane derived from the
half-lifetime was certainly much
lower than that of the corre-
sponding ammonium salt with-
out the rotaxane structure (i.e.,
the axle component) and lower
than those of ethanol and pyr-
role (pKa =15.9 and 17.5, re-
spectively). The occurrence of a
H/D exchange also reveals that
a
free amine-type rotaxane
should be formed as an inter-
mediate, similar to the case of
N-acylation (Scheme 1). In gen-
eral, the use of a stronger base
with ammonium salts should
give free amines, even though
their acidity is very low. How-
ever, many rotaxane chemists
Scheme 1. The formation of a free sec-amine-type rotaxane as an intermediate in N-acylation and H/D ex-
change reactions of 1·PF6.
It is possible to obtain rotaxanes with neutral amine moi-
eties from ammonium salt-type rotaxanes in some special
cases. The first approach involves the introduction of a
second cation station for the metastable state on the axle.
When the axle component of a rotaxane can hold an addi-
tional cationic moiety other than the ammonium salt moiety,
such as a bipyridinium group, treatment with an appropriate
amine base can briefly neutralize the ammonium moiety to
yield a rotaxane with a free amine moiety. By moving the
crown ether wheel to the second cation station, the free am-
monium salt that is not stabilized by the crown ether is read-
ily neutralized, as reported by Stoddart and co-workers.[6]
However, they also reported that a [2]rotaxane with two
sec-ammonium centers could not deprotonate on one am-
monium side, even when four equivalents of amine base
were used.[7a] Leigh and Thomson also reported this behav-
ior.[7b] Another approach involves a removable second
cation station. Tokunaga et al. could neutralize the ammoni-
um moiety by treatment with alkali metal cations capable of
binding to the ligand moiety on the axle as a metastable
state.[8,9] For a simple rotaxane without any additional cat-
ionic station, we reported that N-acylation of the ammoni-
um moiety could yield a neutral rotaxane that possesses
good component mobility,[10] although N-acylation was slow,
even with the use of excess amine and electrophiles.[1,11]
However, these successful neutralization reactions provided
no essential progress toward the synthesis of sec-amine-type
rotaxanes. Nonetheless, we must note the important fact
that a free amine-type rotaxane must be formed as an inter-
mediate during N-acylation. This approach seems to present
a clear possibility for developing free amine-type rotaxanes.
have never succeeded in isolating free amine-type rotaxanes,
even when using very strong bases, as far as we know.[1,7]
Why can no one obtain free amine-type rotaxanes from am-
monium salt-type rotaxanes? Herein, we present a general
answer and propose a method by reporting the first success-
ful synthesis of a free nonionic sec-amine-type rotaxane
from the corresponding sec-ammonium-type rotaxane and
describing the properties of the sec-amine-type rotaxane. In
other words, this study refers to the special rotaxane effect
in which a functional group placed on the axle component
under the strong influence of the wheel component is unusu-
ally well protected by the wheel component in a thermody-
namic fashion that depends on the mobility of the wheel
component in a kinetic fashion. Therefore, this rotaxane
effect may be called dynamic protection. The discovery of
an efficient neutralization protocol will greatly expand the
applicability of crown ether/sec-ammonium-type rotaxanes
as the most easily available rotaxanes. This report answers a
very difficult riddle that has been unsolved for 15 years
since the first crown ether/sec-ammonium salt rotaxane was
reported by Kolchinski et al.[12a] and Ashton et al.[12b]
Results and Discussion
Outline of the neutralization of a sec-ammonium salt-type
rotaxane and a strategy for the isolation of sec-amine-type
rotaxane: In addition to the above discussion, the following
facts are also relevant: 1) A pseudorotaxane is never formed
from a sec-ammonium axle with a chloride counteranion[13]
and 2) the tert-ammonium salt-type rotaxane 4 is relatively
easily neutralized by common bases.[14] The situation is com-
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sec-Amine-Type Rotaxanes
FULL PAPER
plicated because the complex
interaction between the ammo-
nium and crown ether moieties
disappears when the wheel
leaves the ammonium moiety.
Namely, the thermodynamic
property of the acidity of the
ammonium moiety depends
strongly on the kinetic property
of the translation of the wheel;
therefore, once the ammonium
moiety is liberated from the
protection of the crown ether
wheel, it is no longer as spe-
cial.[1,6–8,15]
The reason why a free sec-
amine-type rotaxane has never
been isolated despite the fact
that it is known to form as an
intermediate in N-acylation and
H/D exchange reactions is
clearly because the sec-ammo-
nium salt-type rotaxane is much
more stable than the corre-
sponding free sec-amine-type
rotaxane, although this is not a
typical relationship. The degree
Figure 1. Potential energy diagram of various rotaxane derivatives including 1·PF6 (Scheme 1). Stability of N-
modified forms of each rotaxane system (R=H, Me) can be qualitatively compared.
of stabilization is remarkably large in the case of 1·PF6
(Scheme 1), enough to make the isolation of 2 impossible.
The relative stability of each substance proposed in the pres-
ent discussion can be summarized in the potential-energy di-
agram in Figure 1.
From the results and discussion above, we have concluded
that the free sec-amine-type rotaxane must be isolated from
the sec-ammonium salt-type rotaxane if the remarkably
strong hydrogen bonding between the ammonium moiety on
the axle and the crown ether wheel is sufficiently weakened.
The decrease in strength of hydrogen bonding can be ac-
complished by 1) decreasing the number of hydrogen bonds
and 2) decreasing the cationic character of the nitrogen
atom. That is, both protocols promote the transfer of the
crown ether wheel from the ammonium moiety to elsewhere
on the axle, thus making neutralization easy.
As indicated in Figure 1, the sec-ammonium PF6 salt-type
rotaxane 1·PF6 is stabilized to a similar extent as the N-acy-
lated rotaxane 3 and much more than the free sec-amine ro-
taxane 2. The stability of 1·PF6 is also confirmed by the fact
that pseudorotaxanes with a sec-ammonium axle without
end-cap moieties can sometimes be isolated as stable com-
pounds.[16] Thus, a sec-ammonium compound incorporated
into the crown ether cavity can form an unusually stable
complex. It can be concluded that the acidity of the ammo-
nium group of 1·PF6 is unusually lowered, much more than
that of a general sec-ammonium salt, probably due to highly
effective cation charge delocalization through hydrogen
bonding by rotaxane complexation. However, we believe an
additional effect that lowers the acidity may exist because
the degree of decrease in acidity and stabilization of 1·PF6
are unexpectedly large. This effect is a result of kinetic pro-
tection against proton abstraction from the ammonium
moiety by the crown ether wheel, which acts as a surround-
ing “bulky” group that suppresses neutralization by a
base.[17] In the neutralization of ammonium salts in organic
solvents, it seems most likely that neutralization occurs
through initial ammonium proton abstraction by a basic nu-
cleophile present in the system, but not through direct disso-
ciation to a proton and free amine, especially in the present
system.
As a result, we can list the possible synthetic protocols to
form neutral rotaxanes, which contain the following three
approaches (summarized in Scheme 2):
A) neutralization through N-acylation of an intermediary
free sec-amine-type rotaxane formed in situ under basic
conditions;
B) neutralization by decreasing the cationic character of
the ammonium moiety by counteranion exchange;
C) neutralization through weakened hydrogen-bonding in-
teractions by decreasing the number of hydrogen atoms
capable of participating in bonding.
We have already successfully implemented approach A in
Scheme 2 in the selective N-acylation of 1·PF6 in the pres-
ence of excess electrophile and base to 3.[1,11] This approach
consists of trapping a very small amount of “unstable” inter-
mediate 2 formed in equilibrium with 1·PF6 with an electro-
phile. We have also recently succeeded in obtaining a free
Chem. Eur. J. 2010, 16, 13783 – 13794
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13785

T. Takata and K. Nakazono
Scheme 2. Possible synthetic protocols to form neutral rotaxanes.
tert-amine-type rotaxane by decreasing the number of hy-
drogen bonds from two to one.[14] Specifically, N-methyla-
tion of 1·PF6 yielded the tert-ammonium salt-type rotaxane
4·PF6 (R=H), which turned out to be easily neutralizable to
the tert-amine-type rotaxane 5 (R=H) by treatment with a
typical amine base (approach C in Scheme 2). The weak-
ened hydrogen bonding in 4·PF6 was confirmed by the fact
that a much less appreciable amount of the inclusion com-
plex (pseudorotaxane) was formed between the tert-ammo-
nium salt axle and dibenzo[24]crown-8 ether (DB24C8).[14]
The activation energy from the N-methylated tert-ammoni-
um PF6-type rotaxane 4·PF6 to free tert-amine-type rotaxane
5 should be much smaller than that from 1·PF6 to 2, as
judged from its ease of neutralization (Figure 1). The small
activation energy is supported by the fact that reversible
acidification/neutralization of 5 has been attained.[14]
Synthesis of sec-amine-type rotaxane 2 by neutralization
through counteranion exchange: As mentioned above, the
difficulty of neutralization, that is, the unusual stabilization
of 1·PF6, should come from not only delocalization of the
cationic charge through hydrogen bonding, but also the
steric-protection effect of the crown ether wheel against
proton abstraction in an organic solvent. The former is ther-
modynamic stabilization, whereas the latter is kinetic stabili-
zation. This type of kinetic stabilization may be due to the
exceptionally specific circumstances seen in interlocked sys-
tems, such as rotaxanes. We previously reported that N-acy-
lation with a bulky electrophile causes wheel migration to
the less-crowded side of the axle in the resulting rotax-
ane.[1,11] This behavior indicates that the acylating agent at-
tacks exclusively from the more-crowded side.[15d] By consid-
ering the possibility of ammonium proton abstraction with a
base in 1·PF6, basic species must slowly attack the proton on
the lower charged cation, probably from the more-crowded
side, to move the wheel to the less-crowded side. Therefore,
the attack should take place more slowly than reverse proto-
nation of the free sec-amine-type rotaxane product 2. Thus,
Although the isolation of the genuinely free amine-type
rotaxane 2 remained a major target, the neutralization suc-
cessfully proceeded to give 2 in a quantitative yield through
approach B by decreasing the cationic character of the sec-
ammonium group (described later in detail).
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sec-Amine-Type Rotaxanes
FULL PAPER
Table 1. One-pot neutralization of sec-ammonium rotaxane 1·PF6 with
we first examined neutralization by using a small nucleophil-
ic base to cause the crown ether wheel to migrate from the
ammonium salt center. An attempted neutralization with a
hydride ion as the smallest nucleophilic base, namely, the
various salts.[a]
Entry Anion-exchanging
agent
Conditions
Conversion
yield[b] [%]
(equiv to rotaxane)
treatment of 1·PF6 with NaBH3CN or NaBHACTHUNTRGNEU(GN OAc)3, yielded
1
2
3
4
KF (50)
CsF (2.4)
THF/H2O (5/1)
DMF
THF
THF
THF
THF
10% H2O/
[D6]DMSO
708C
RT
RT
RT
RT
RT
RT
0
0
100
80
no corresponding neutralized sec-amine-type rotaxane 2,
only 1·PF6. The hydride donor did not work adequately as a
TBAF (1.2)
TBACl (1.2)
TBABr (1.2)
TBAF (3.0)
TBAOH (2.0)
À
scavenger of HPF6, nor could it remove the PF6 ion, with
5
44
original as discussed later.
6[c]
7
97[d]
From the unsuccessful results with the hydride donor, we
turned our attention to anion exchange for the successful re-
[e]
–
À
moval of the PF6 ion from the reaction system. A small,
[a] Each anion exchange agent (or its solution) was added to the sec-am-
monium PF6 salt-type rotaxane 1·PF6 (50 mmol) dissolved in 0.5 mL of
solvent. Each mixture was then washed well with aqueous Na2CO3.
[b] The conversion ratio was determined by 1H NMR spectroscopic anal-
ysis. [c] The sec-ammonium fluoride-type rotaxane 1·F that formed was
isolated by directly pouring the reaction mixture into diethyl ether (97%
yield). [d] Yield of the isolated product. [e] Starting material 1·PF6 was
gradually decomposed. Free crown ether was confirmed by the 1H NMR
spectrum.
hard anion was selected as a new partner counteranion for
1·PF6, which would be capable of forming a hydrogen bond
with the ammonium moiety instead of the crown ether
wheel, because it is known that small, hard anions can di-
rectly connect to the ammonium group through hydrogen
bonding.[13] If the introduction of a small, hard counteranion
removes the strong interaction between the crown ether and
the ammonium group to eject the crown ether wheel to else-
where on the axle, the resulting ammonium salt should
become an ordinary acid that is weak enough to be neutral-
ized with typical bases. The degree of dissociation equilibri-
um of an anion/ammonium complex can be explained by the
HSAB rule: the harder the anion is, the more strongly it in-
teracts with ammonium hydrogen atoms. Thus, anion ex-
change seems to be an effective way to decrease the kinetic
acidity of the ammonium salt.
TBAF, in good accordance with our expectations, whereas it
clearly depended on the kind of halide counteranion used,
which is consistent with the HSAB theory. Namely, the con-
version yield decreased proportionally on the order of ion
size (i.e., 100>80>44% for F>Cl>Br, respectively),
which was determined from the signals observed by
1H NMR spectroscopic analysis and that were assigned to
the oxybenzylic proton signal h at d=5–6 ppm.
However, we could not isolate 2 from the reaction mix-
ture by typical isolation procedures, such as chromatograph-
ic purification and recrystallization, even though the coun-
teranion exchange of 1·PF6 followed by neutralization of 1·F
was successfully achieved, as
The anion-exchange experiment was carried out by
mixing 1·PF6 with one of several salts with small anions at
room temperature in an organic solvent followed by washing
the resulting mixture with saturated sodium hydrogen car-
bonate for neutralization (Scheme 3 and Table 1). Table 1
seen by 1H NMR spectroscopy
(see above). The final product
obtained in hand was always
1·PF6. We eventually concluded
that the present phenomenon
must result from the much
higher stability of 1·PF6 relative
to 2 or 1·F. Therefore, we exam-
ined the isolation of 2 after the
À
complete removal of PF6 ions
Scheme 3. Neutralization through counteranion exchange.
in the form of TBAPF6. When a
reaction mixture that contains
shows that potassium and cesium fluoride salts were ineffec-
tive (Table 1, entries 1 and 2), whereas tetrabutylammonium
fluoride (TBAF) resulted in complete neutralization to free
the products 1·F and TBAPF6 along with excess TBAF was
poured directly into a large quantity of diethyl ether, rotax-
ane 2 could be isolated in 97% yield as the sole soluble sub-
stance. As an alternative method, initial filtration of the re-
action mixture with celite followed by washing with aqueous
Na2CO3 was also effective enough to give pure 2 in 97%
yield.
sec-amine-type rotaxane
2 (100% conversion; Table 1,
entry 3). The spectral change on the addition of TBAF to a
solution of 1·PF6 in CHCl3 at room temperature was moni-
tored and clearly suggested the formation of the ammonium
fluoride-type rotaxane 1·F by the emergence of new signals
that were different from those of 1·PF6, which agreed well
with the structure of 2. The conversion of the anion ex-
change from 1·PF6 into 1·F was 100% with the use of
1
The structure of 2 was determined by H NMR and IR
spectroscopy and a titration experiment (the details are
1
given later). In relation to the H NMR spectra of 1·PF6 and
2, the disappearance of the broad signal assigned to the NH2
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13787

T. Takata and K. Nakazono
À
À
group and large upfield shift of the N CH2 signals due to
removal of PF6 ions from the system due to the fast reverse
deprotonation of the ammonium salt moiety were con-
firmed. Other signals were easily assigned to those expected
for 2, which were comparable with those of the tert-amine-
conversion of 2 into 1·PF6 owing to its extraordinary stabili-
ty. The most effective and easy method for removing PF6
À
ions should be the acylation of 1·PF6 (Scheme 2) because of
the high stability of product 3, as discussed previously
(Figure 1). Therefore, we adopted the synthesis of 2 based
on the carbamate protection/deprotection protocol as an al-
ternative. Roxtane 1·PF6 was transformed into N-trichloroe-
thylcarbamoyl derivative 3Troc in 89% yield by treatment
with 2,2,2-trichloroethyl chloroformate (TrocCl) and trie-
thylamine in THF at room temperature (the protection step;
Scheme 4).[15d] Derivative 3Troc was deprotected with active
zinc in acetic acid to give sec-ammonium acetate 1·OAc,
which was washed with aqueous Na2CO3 to afford 2 in 96%
overall yield, similar to that of the anion-exchange method
mentioned above. The present synthetic method for the neu-
tral rotaxane might be useful in various systems because
neutral intermediate rotaxanes can be isolated.
The structures of the intermediate rotaxanes 3Troc and
1·OAc were determined from various spectroscopic analyses.
Figure 2 shows the NMR spectra of four rotaxanes related
to the sec-amine-type rotaxane 2 in Scheme 4. The top spec-
trum of 2 agreed well with the spectrum of 2 obtained from
counteranion exchange as described above. Spectra (b) and
(c) in Figure 2 correspond to the precursors 1·OAc and
3Troc, respectively, and are reasonably assignable. In partic-
ular, 1·OAc was almost the same as 1·PF6, although 1·OAc
can be deprotonated by Na2CO3. This difference is invisible
in the spectra. However, a large difference in the intramo-
lecular dissociation equilibrium of the crown ether and am-
monium moiety can be observed.
type rotaxane 5. Furthermore, the typical absorptions of the
P F bond at n˜ =841 and 557 cm completely disappeared
in the IR spectrum. Finally, rotaxane 2 was treated with
HPF6, and the resulting product showed a 1H NMR spec-
trum fully coincident with that of 1·PF6.
À1
À
To rule out the possibility of direct neutralization with
TBAOH formed in situ as the decomposition product of
TBAF, 1·PF6 was treated with an equimolar amount of
TBAOH (0.4m in HO) in ([D6]DMSO) at ambient tempera-
ture. An 1H NMR spectrum of the reaction mixture after
10 minutes indicated the formation of not only the sec-
amine-type rotaxane 2 but also free DB24C8 as a decompo-
sition product of 1·PF6. Further addition of TBAOH in-
duced a significant increase in the ratio of free DB24C8,
thus indicating competitive decomposition of the axle
moiety of 1·PF6, possibly through hydrolysis. This result,
along with the quantitative formation of 2 by the use of
TBAF, rules out the participation of TBAOH.
The transformation of 1·PF6 into 2 or the isolation of 2,
which has been long believed to be impossible, was first ac-
complished in this study by changing the counteranion of
the ammonium salt unusually stabilized by the crown ether
wheel to the common ammonium salt uncovered by the
crown ether wheel. This exchange was carried out by an ini-
tial counteranion exchange with fluoride anions followed by
neutralization with a typical alkali and skillful removal of
À
the PF6 ions.
Synthesis of 2 through a protection/deprotection protocol:
The above-mentioned synthesis of 2 requires the complete
Structural study of sec-amine-type rotaxane: One of the
most interesting things about neutral rotaxane 2, prepared
Scheme 4. The synthesis of 2 based on carbamate protection/deprotection.
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sec-Amine-Type Rotaxanes
FULL PAPER
structural change. In spectrum
(a) of 1·PF6, a couple of multip-
let signals at around d=
4.5 ppm (i.e., d and e) are char-
acteristic of benzylic proton sig-
nals of the sec-ammonium
moiety encapsulated by the
crown ether wheel through hy-
drogen bonding (Figure 3a).[6,18]
À
Therefore, both N CH2 signals
(i.e., d and e) of 1·PF6 are shift-
ed by approximately Dd=
0.7 ppm upfield in 2 as a result
of neutralization. Such a big
shift corresponds to the loss of
cationic charge at the nitrogen
atoms, thus indicating cancella-
tion of the attractive interaction
with the crown ether wheel. A
further upfield shift of signals d
and e to around d=3.4 ppm is
Figure 2. 1H NMR spectra of rotaxanes a) 2 , b) 1·OAc, c) 3Troc, d) 1·PF6 (400 MHz, CDCl3, 298 K).
first in this study, is the relative positions of its components.
Here, the structure and position or mobility of the compo-
confirmed in spectrum (c) of the tert-amine-type rotaxane 5
(R=Me), which is consistent with the electron-donating
effect of a methyl group (Figure 3c). This shift is also consis-
tent with the above discussion that a rather large downfield
shift of proton signals d and e is
nents of 2 are discussed relative to a few related rotaxanes
1
by using NMR spectroscopy. The H NMR spectrum of 2 is
shown in Figure 3b along with other rotaxanes.
confirmed for the acetamide-
type rotaxane 3Ac (R=Ac), al-
though syn–anti stereoisomer-
ism around the amide moiety of
3Ac causes splitting of all sig-
nals (Figure 3d).
It is important to note the de-
shielding effect of the crown
ether wheel, which seems to be
a good probe for its position on
the axle of the rotaxane.[11,19]
We noticed a singlet signal at
around d=5–6 ppm assignable
to the O-benzyl protons (signal
h). As shown by the spectra (a–
d) in Figure 3,
a significant
chemical-shift difference for
signal h can be confirmed, even
though no big chemical change
is conceived of at this position
far from the nitrogen atom. The
difference obviously corre-
sponds to the difference in the
deshielding effect of the wheel
Figure 3. 1H NMR spectra of rotaxanes a) 1·PF6, b) 2, c) 5, d) 3Ac (400 MHz, CDCl3, 298 K).
Figure 3b shows signals easily assigned to the structure of
the free sec-amine-type rotaxane 2. For example, two aryl
methyl signals appear at around d=2.2 and 2.3 ppm, where-
as the crown ether methylene signals (a–g) are observed at
d=2.9–4.1 ppm with split g proton signals. Characteristic
signals are the benzylic proton signals d, e, and h, which are
shifted considerably relative to 1·PF6 in accordance with the
component toward the O-benzyl moiety. Therefore, the
downfield shift of signal h means that the crown ether wheel
is localized around the O-benzyl moiety to some extent.[11]
1
Comparison of the H NMR spectra of the tert-amine- and
amide-type rotaxanes 5 and 3Ac (Figure 3c,d, respectively)
with 2 seems to suggest the presence of weak hydrogen
bonding of NH···O, which explains some of the upfield shift
Chem. Eur. J. 2010, 16, 13783 – 13794
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13789

T. Takata and K. Nakazono
of signal h in 2 relative to 5 and 3Ac. This discussion is
based on the fact that the crown ether wheel is localized at
the O-benzyl moiety in the X-ray crystal structure analyses
O-benzyl moiety and translates to the amine moiety in a
rapid equilibrium at a higher temperature. The chemical
shift of signal h was shifted upfield with an increase in the
degree of wheel translation to the amine moiety. The trans-
lation reached thermal equilibrium at above 508C, and the
chemical shift settled at approximately d=5.5–5.4 ppm. In
the control VT-NMR experiments, both the sec-ammonium
salt-type rotaxane 1·PF6 and tert-amine-type rotaxane 5
showed no such temperature-dependent behavior. Thus, the
present VT-NMR spectroscopic studies clearly demonstrat-
ed an excellent dynamic property of the sec-amine-type ro-
taxane, thus strongly suggesting the significance of the neu-
tralization of sec-ammonium-type rotaxanes or the synthesis
of sec-amine-type rotaxanes.
Other signals of the axle also shifted reasonably with the
temperature change. The phenylene and ortho-protons of
the dimethylbenzoyl group (i.e., signals g and i, respectively)
were shifted upfield by Dd=0.3–0.7 ppm from approximate-
ly d=8 ppm with decreasing temperature. The chemical-
shift changes are derived from the deshielding effect of the
crown ether wheel with attractive interactions with parts of
the axle.[10] Protons at the opposite side of the axle, such as
N-benzyl protons h, were shift-
of 5[14] and 3Ac,[11] in which weak interactions such as C
À
À
H···p and C H···O are probably operative, in accordance
with the NMR results.
From the above discussion, we can conclude in simple
terms that the crown ether wheel has the highest probability
of existing at a position on the axle with which it has the
strongest attractive interaction. The position evaluated by
NMR spectroscopy, therefore, should be a mean position
that results from fast translation on the axle. Thus, the
wheel of 2 might possess a few stations as local minima on
the axle; therefore, the chemical shift of signal h in 2 in the
NMR spectra appears between those of 1·PF6 and 5 or 3Ac,
thus suggesting the wheel component is localized at the
phenylene moiety of the axle component.
Dynamic nature of sec-ammonium-type rotaxane 2: A varia-
ble-temperature (VT) NMR spectroscopic study of 2 was
carried out to examine the dynamic nature of the free
amine-type rotaxane in detail (Figure 4). An interesting fea-
ed downfield with increasing
temperature by Dd=0.2 ppm
from approximately d=3.8 ppm
with a little splitting. Both up-
field and downfield shifts clear-
ly correspond to the movement
of the wheel from the O-benzyl
ester moiety to the phenylene
group. In good agreement with
the change in the axle proton
signal, the wheel proton signals,
in particular two split g proton
signals, approached each other,
which is consistent with the in-
creasing symmetry of the axle
with the movement of the
wheel. The present discussion
might be reasonably supported
by the sharp signals in all the
spectra obtained over the tem-
perature range studied, thus
suggesting fast translation and
circumrotation of the rotaxane
Figure 4. VT-NMR spectrum of rotaxane 2 (1HNMR, 400 MHz, CDCl3).
wheel (when the axle is fixed).
ture of signal h was confirmed: the signal was shifted down-
field by cooling and finally shifted to d=6 ppm at À508C.
On the other hand, the signal moved to d=5.5 ppm with
heating to 508C. Here, the chemical species involved in the
system should be single because each signal was quite sharp
over the temperature range examined. The wheel compo-
nent is likely to be localized at a thermodynamically stabi-
lized position, that is, the O-benzyl moiety, at a lower tem-
perature, whereas it becomes free from interactions at the
Neutralization of bis(ammonium salt)-type [3]rotaxane:
Neutralization of a bis(ammonium salt)-type [3]rotaxane by
a similar procedure was examined to confirm the scope and
limitations of the present neutralization protocol. This inves-
tigation is very important for obtaining information on ap-
plicability to oligo- and polyrotaxanes. The synthesis of
[3]rotaxane 6·PF6 was performed according to our previous-
ly reported method that employed pseudo[3]rotaxane and
3,5-di-tert-butylbenzoic anhydride by using tributylphos-
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Chem. Eur. J. 2010, 16, 13783 – 13794

sec-Amine-Type Rotaxanes
FULL PAPER
Scheme 5. Neutralization of a bis(ammonium salt)-type [3]rotaxane.
phine-catalyzed end-capping (Scheme 5).[20] [3]Rotaxane
6·PF6 was similarly treated with 3.0 equivalents of TBAF
and worked up according to the optimized conditions men-
tioned above. As a result, 7 was successfully isolated as a
white powder without any other product, such as 6·F. The
structure of 7 was confirmed by 1H NMR spectroscopy
(Figure 5). The characteristic signal h of the wheel position
was shifted downfield from d=5.24 to 5.56 ppm by this neu-
tralization reaction. Other proton signals also indicated the
proposed structure of 7. Thus, the present neutralization
protocol involving an initial anion exchange with TBAF fol-
lowed by washing with an aqueous solution of a base was
also useful for neutralizing a more complicated rotaxane,
namely, [3]rotaxane.
Neutralization mechanism: The successful isolation of the
sec-amine-type[2]rotaxane 2 in this study realized the gener-
ation of a crown ether/sec-amine-based rotaxane almost free
from strong intercomponent interactions. Here, we would
like to discuss the mechanism of this neutralization in detail.
The fact that 1·F is readily neutralized to 2 with a simple
base, whereas 1·PF6 is never neutralized with any base,
raises the question of why 1·F is so much more unstable
than 1·PF6 or why 1·F has a much higher potential energy
than 1·PF6. The answer can be derived from detailed analy-
sis of the neutralization mechanism (Scheme 6). There are
several possible species for the counteranion exchange. Ro-
taxane 1:PF6, a structural isomer of 1·PF6 with an uncovered
ammonium moiety, is possible, but scarcely plays a role in
the equilibrium shown in
Scheme 6 because of its insta-
bility. From the low acidity of
HF relative to HPF6, not only
1·F but also 1:F, with an uncov-
ered ammonium moiety, and
nonionic 1 F, consisting of
NH···F hydrogen bonds, are
also much more unstable than
1·PF6. Judging from the fact
that neutral sec-amine rotaxane
2 is actually observed as the
only species in the counteran-
ion-exchange system, even with
the use of 1.0 equivalent of
TBAF, the product species (i.e.,
2+Bu4N+PF6À +HF) should be
more stable than the starting
species (i.e., 1·PF6 +Bu4N+FÀ).
However, no such extra stabili-
ty seems to appear in the prod-
uct species when compared
Figure 5. 1H NMR spectra of [3]rotaxanes a) 6·PF6 and b) 7 (400 MHz, CDCl3, 298 K).
Chem. Eur. J. 2010, 16, 13783 – 13794
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13791

T. Takata and K. Nakazono
Scheme 6. Prospective neutralization mechanism of 1·PF6 to 2 via 1·F and related species 1:F and 1_F in organic solvent.
À
with the species 1:F+Bu4N+PF6 , which is clearly inconsis-
tent with the formation of 2. One possible answer may con-
firm the experimental findings by assuming a leak process in
the equilibrium of Scheme 6. Namely, it is considered that
HF can no longer form an adduct with 2, such as 1·F and
1:F, once liberated because HF is a weak acid in DMSO
(pKa =15).[21,22] Thus, the formation of 2 by counteranion ex-
change can be rationalized by assuming special stabilization
of 1·F that leads to 2 with the liberation of HF. The starting
species 1·PF6 +Bu4N+FÀ becomes more unstable than the
Conclusion
As discussed herein, we have succeeded for the first time in
isolating nonionic free sec-amine-type rotaxanes from sec-
ammonium salt-type rotaxanes by using a protocol based on
the unique nature of the rotaxanes, although no one had
prepared such simple free amine rotaxanes so far. By using
energy diagrams, the neutralization can be explained as fol-
lows (Figure 1 and Scheme 6): The sec-ammonium salt-type
rotaxane is highly stabilized toward a base for several rea-
sons. First, the ammonium salt-type rotaxane forms strong
hydrogen bonds with the crown ether wheels, which brings
about effective delocalization of the cation charge. This be-
havior results in thermodynamic stabilization. Second, the
crown ether wheel that covers the ammonium group acts as
a bulky group to largely prevent attack on the proton of the
ammonium group or decrease the proton dissociation rate
to a large extent in an organic solvent. This behavior results
in kinetic stabilization. These two different effects work to-
gether in the rotaxane system to provide the extraordinary
stability of the ammonium moiety. Therefore, the effect of
the counteranion on the stabilization is significantly ampli-
fied in organic solvents; we call this the rotaxane effect.
Both effects are deeply related and inseparable from each
product species 2+Bu4N+PF6À[+HF]. Therefore, the isola-
ACHTUNGRTENNUGN
tion of 1·F (or 1:F) as a stable product is impossible in this
system. In fact, the H NMR spectrum of 1·F that we first
considered was practically the same as 2.
1
An excess amount (3 equiv) of TBAF is required because
TBAF is used to suppress the highly favorable formation of
1·PF6 with a contaminated source of H+ ions other than HF,
such as water, during the isolation process because PF6À ions
À
still remain as Bu4N+PF6 in the system. Specifically, TBAF
would convert some protonic species, such as H2O into HF,
which does not promote the formation of 1·PF6.
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Chem. Eur. J. 2010, 16, 13783 – 13794

sec-Amine-Type Rotaxanes
FULL PAPER
rator and drying in vacuo to obtain 2 as the residual colorless solid
(50 mg, 100% yield). M.p. 1348C; 1H NMR (400 MHz, CDCl3, 298 K):
d=7.88 (s, 2H), 7.56 (d, J=7.8 Hz, 2H), 7.29 (d, J=7.8 Hz, 2H), 7.14 (s,
1H), 6.98 (s, 2H), 6.89–6.81 (m, 8H), 6.77 (s, 1H), 5.57 (s, 2H), 4.08 (t,
J=4.4 Hz, 8H), 3.95 (s, 2H), 3.87 (s, 2H), 3.78–3.69 (m, 8H), 3.36–3.30
(m, 4H), 3.25–3.19 (m, 4H), 2.29 (s, 6H), 2.18 ppm (s, 6H); 13C NMR
(100 MHz, CDCl3, 298 K): d=167.0, 148.4, 141.5, 140.6, 137.8, 137.2,
134.6, 134.3, 130.5, 128.2, 128.0, 127.8, 126.4, 125.5, 120.6, 111.8, 69.7,
69.4, 67.8, 66.9, 52.9, 30.3, 21.2, 21.0 ppm; IR (KBr): n˜ =3163, 2919, 2879,
1713, 1505, 1454, 1311, 1251, 1215, 1124, 1053, 742 cmÀ1; FAB-HRMS
calcd for C50H61NO10 836.4374 [M+H]+; found: 836.4343.
other. Our present protocol, which involves the counteran-
ion-exchange method in addition to decreasing the number
of hydrogen bonds,[13] could solve a significant problem that
had remained unsettled for 15 years. Counteranion exchange
causes a major structural change in sec-ammonium rotax-
anes due to the special nature of HF, which was liberated
from the system to remarkably enhance the stability of the
product species relative to the starting species in the entire
equilibrium. As a result, the sec-amine-type rotaxane was
obtained quantitatively. Not only a [2]rotaxane but also a
[3]rotaxane were completely neutralized to the correspond-
ing sec-amine-type rotaxanes. This protocol will be applica-
ble to the construction of various rotaxane-based supra-
molecular and polymer architectures. The rotaxane effect
can be regarded as one of the dynamic steric protections
often found in interlocked systems.
Neutralization through a protection/deprotection protocol
Preparation of N-Troc [2]rotaxane 3Troc: Triethylamine (0.35 mL,
2.5 mmol) and 2,2,2-trichloroethyl chloroformate (0.27 mL, 2.0 mmol)
were added to a solution of [2]rotaxane 1·PF6 (0.49 g, 0.5 mmol) in THF
(5 mL) at room temperature. The solution was stirred for 19 h at room
temperature and the reaction mixture was diluted with dichloromethane
(10 mL) and water (5 mL). The organic layer was washed with 3m HCl,
water, 5% Na2CO3, and brine. After the mixture had been dried over an-
hydrous MgSO4 and filtered, the solvent was removed under reduced
pressure. The crude product was purified by preparative gel permeation
chromatography (GPC) with CHCl3 as the eluent to obtain 3Troc as a
colorless solid (0.45 g, 89% yield). M.p. 1008C; 1H NMR (400 MHz,
CDCl3): d=8.18 (m, 2H), 8.12 (m, 2H), 7.09 (s, 1H), 7.03 (d, J=8.0 Hz,
2H), 6.90–6.81 (m, 12H), 6.00 (m, 2H), 4.81 (s, 1H), 4.72 (s, 1H), 4.33
(m, 2H), 4.25 (s, 2H), 4.12–4.03 (m, 8H), 3.76–3.72 (m, 4H), 3.66–3.62
(m, 4H), 3.30–3.27 (m, 4H), 2.96–2.90 (m, 4H), 2.27 (s, 6H), 2.20 ppm (s,
6H); 13C NMR (100 MHz, CDCl3): d=167.0, 154.8, 154.7, 148.5, 138.1,
137.6, 137.5, 137.3, 136.8, 134.1, 133.9, 130.8, 129.2, 129.1, 128.2, 127.0,
126.8, 125.8, 125.7, 120.5, 120.4, 111.5, 95.8, 75.2, 69.5, 69.3, 67.9, 66.8,
49.3, 48.9, 48.8, 48.2, 21.2, 20.8 ppm; IR (KBr): n˜ =2920, 1716, 1505, 1454,
1310, 1251, 1218, 1125, 1052, 738 cmÀ1; elemental analysis calcd for
C53H62Cl3NO12: C 62.94, H 6.18, N 1.38; found: C 62.85, H 6.12, N 1.57;
Experimental Section
Measurements: Melting points were measured on a melting-point appara-
tus SMP3 instrument (Stuart Scientific). The 1H and 13C NMR spectra
were recorded on a JEOL AL-400 NMR spectrometer operating at 400
and 100 MHz, respectively, in CDCl3 with tetramethylsilane (TMS) as an
internal standard. The NMR chemical shifts were reported in delta units
d. Multiplicity is indicated by s (singlet), d (doublet), t (triplet), m (mul-
tiplet), or br (broad). The coupling constants J are reported in Hz. The
IR spectra were measured by a JASCO FT/IR-460 plus spectrometer.
Preparative HPLC was carried out on a JAI HPLC LC-918 instrument
(columns: JASCO Megapack-Gel 201C, Megapack-Gel 201 CP, and JAI
JAIGEL-1H; eluent: CHCl3; flow rate: 3.5 mLminÀ1). The mass spectra
were recorded on a JEOL JMS-700 instrument with meta-nitrobenzyl al-
cohol as the matrix. Elemental analyses were carried out on a LECO
CHNS-932 instrument.
FAB-HRMS calcd for C53H62Cl3NO12
1032.3235.
:
1032.3215 [M+Na]+; found:
Preparation of 1·OAc: Activated zinc powder (0.2 g, 3.0 mmol) was
added to 3Troc (0.3 g, 0.3 mmol) dissolved in acetic acid (3 mL). The sus-
pension was stirred vigorously for 3 h at room temperature. The suspen-
sion was diluted with CHCl3 (10 mL) and zinc powder was removed by
filtration. The combined filtrate was washed with water and brine. After
drying over anhydrous MgSO4, the solvent was removed under reduced
pressure. The residue was used without further purification (0.26 g, 97%
yield). M.p. 1238C; 1H NMR (400 MHz, [D6]DMSO): d=7.60 (s, 2H),
7.35 (br, 4H), 7.29 (s, 1H), 6.92–6.89 (m, 4H), 6.86–6.83 (m, 4H), 6.79 (s,
3H), 5.26 (br, 2H), 4.55 (br, 2H), 4.44 (br, 2H), 4.04 (br, 8H), 3.69 (br,
8H), 3.43 (br, 8H), 2.31 (s, 6H), 2.04 (s, 6H), 1.78 ppm (s, 3H); 13C NMR
(100 MHz, [D6]DMSO): d=172.6, 165.7, 147.2, 138.1, 137.4, 134.8, 129.6,
129.5, 127.8, 126.9, 126.5, 121.0, 112.4, 70.0, 69.7, 67.6, 65.6, 51.8, 51.6,
22.2, 20.8, 20.7 ppm; IR (KBr): n˜ =3422, 2921, 5873, 1717, 1506, 1458,
Materials: All the solvents were distilled before use according to general
purification procedures. Commercially available reagents were used with-
out further purification unless otherwise noted. Column chromatography
was performed on Wakogel C-400HG. Rotaxane 1·PF6 was prepared ac-
cording to the reported procedures.[10]
Neutralization through an anion-exchange reaction (Table 1, entry 6)
Preparation of 1·F: TBAF in THF (0.30 mL, 0.30 mmol, 1.0m) was added
to
a solution of sec-ammonium PF6-type rotaxane 1·PF6 (98 mg,
0.10 mmol) in THF (1.0 mL). The solution was stirred at room tempera-
ture for 30 min under air. Diethyl ether (5 mL) was added to the solution
and the reaction mixture was stirred vigorously in an ice bath. The pre-
cipitate was removed by filtration and washed with diethyl ether. The
combined filtrate was concentrated on a rotary evaporator and dried in
vacuo to obtain 1·F as the residual colorless solid (83 mg, 97% yield),
which was used without further purification in the neutralization reac-
tion. 1H NMR (400 MHz, CDCl3, 298 K): d=7.88 (s, 2H), 7.56 (d, J=
7.9 Hz, 2H), 7.28 (d, J=7.9 Hz, 2H), 7.13 (s, 1H), 6.97 (s, 2H), 6.88–6.80
(m, 8H), 6.77 (s, 1H), 5.58 (s, 2H), 4.07 (t, J=4.5 Hz, 8H), 3.92 (d, J=
5.5 Hz, 2H), 3.84 (d, J=5.5 Hz, 2H), 3.78–3.69 (m, 8H), 3.35–3.29 (m,
4H), 3.23–3.17 (m, 4H), 2.34 (s, 6H), 2.28 ppm (s, 6H); 13C NMR
(100 MHz, CDCl3, 298 K): d=167.0, 148.4, 141.4, 140.4, 137.8, 137.2,
134.6, 134.3, 130.5, 128.1, 128.0, 127.8, 127.7, 126.3, 1205., 111.7, 69.6,
69.4, 67.8, 66.9, 53.1, 53.0, 21.2, 21.0 ppm; IR (KBr): n˜ =3323, 2918, 2876,
1713, 1505, 1454, 1312, 1251, 1217, 1125, 1054, 742 cmÀ1; FAB-HRMS
calcd for C50H62FNO10: 836.4374 [MÀF]+; found: 836.4394.
1308, 1253, 1214, 1122, 1055, 953, 746 cmÀ1
; FAB-HRMS calcd for
C52H65NO12: 836.4374 [MÀOAc]+; found: 836.4386.
Neutralization of 1·OAc (preparation of 2): A solution of 1·OAc (0.26 g,
0.29 mmol) in THF (5 mL) was neutralized by washing with saturated
aqueous Na2CO3. The organic layer was washed with brine and dried
over anhydrous MgSO4. After the solvent was removed, 2 was obtained
as a colorless solid (240 mg, 99% yield).
Preparation of [3]rotaxane 6·F: TBAF (1.8 mmol) in THF (1.0m, 1.8 mL)
was added to a solution of 6·PF6 (0.60 g, 0.30 mmol) in THF (3.0 mL) at
room temperature, and the solution was stirred for 30 min. After the sol-
vent was removed under reduced pressure, the residue was extracted
with diethyl ether. The insoluble part was removed by filtration through
celite. The combined filtrate was concentrated under reduced pressure.
The residue was purified by reprecipitation from diethyl ether/hexane.
The combined colorless powder 6·F (0.43 g) was used without further pu-
rification.
Preparation of sec-amine-type [2]rotaxane 2: Compound 1·F (50 mg,
58 mmol) was dissolved in THF (0.5 mL) and stirred vigorously with 10%
Na2CO3 (5.0 mL) for 5 min at room temperature. The aqueous layer was
extracted with diethyl ether and the combined organic layers were dried
over anhydrous MgSO4, followed by solvent removal on a rotary evapo-
Preparation of amine-type [3]rotaxane 7:[3] Aqueous Na2CO3 (1.0 g in
10 mL H2O) was added to 6·F (0.43 g) dissolved in diethyl ether (10 mL),
and the reaction mixture was stirred vigorously for 10 min. After separa-
Chem. Eur. J. 2010, 16, 13783 – 13794
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13793

T. Takata and K. Nakazono
tion of the organic layer, the aqueous layer was extracted with CHCl3.
The combined organic layer was dried over anhydrous MgSO4, filtered,
and concentrated in vacuo to obtain 7 as a colorless solid (0.42 g,
[8] Y. Tokunaga, T. Nakamura, M. Yoshioka, Y. Shimomura, Tetrahe-
dron Lett. 2006, 47, 5901–5904.
[9] Rotaxanes that possess a crown ether with nitrogen atoms instead of
oxygen atoms, such as the 2,6-bis(aminomethyl)pyridine group-con-
taining macrocycle, could be neutralized with aqueous NaOH as
shown by Stoddart and co-workers; a smaller association constant of
the macrocycle than that of DB24C8 is suggested: a) P. T. Glink,
A. I. Oliva, J. F. Stoddart, A. J. P. White, D. J. Williams, Angew.
Chem. 2001, 113, 1922–1927; Angew. Chem. Int. Ed. 2001, 40, 1870–
1875; b) J. Wu, K. C.-F. Leung, J. F. Stoddart, Proc. Natl. Acad. Sci.
USA 2007, 104, 17266–17271.
1
0.25 mmol, 82% yield over 2 steps). Mp 116–1208C; H NMR (400 MHz,
CDCl3, 298 K): d=8.02 (d, J=1.8 Hz, 4H), 7.59 (t, J=1.8 Hz, 2H), 7.56
(d, J=8.0 Hz, 4H), 7.30 (d, J=8.0 Hz, 4H), 6.84–6,76 (m, 16H), 5.56 (s,
4H), 4.06 (br s, 16H), 3.78 (s, 4H), 3.76 (br s, 16H), 3.34–3.31 (m, 8H),
3.23–3.22 (m, 8H), 2.56 (t, J=7.4 Hz, 4H), 1.33 (m, 4H), 1.30 (s, 36H),
1.07 ppm (br s, 4H); 13C NMR (100 MHz, CDCl3, 298 K): d=167.4,
150.9, 148.4, 141.0, 134.1, 130.1, 128.4, 128.3, 128.0, 127.9, 126.8, 124.0,
123.9, 120.5, 111.8, 69.9, 69.7, 69.5, 67.8, 67.0, 53.1, 49.7, 34.9, 31.3, 30.3,
27.8 ppm; IR (KBr): n˜ =3435, 2959, 2924, 2871, 1715, 1593, 1505, 1454,
[10] N. Kihara, Y. Koike, T. Takata, Chem. Lett. 2007, 36, 208–209.
[11] Y. Tachibana, H. Kawasaki, N. Kihara, T. Takata, J. Org. Chem.
2006, 71, 5093–5104.
1251, 1126, 1055, 741 cmÀ1
1685.9765 [M+H]+; found: 1685.9788.
; FAB-HRMS calcd for C100H136N2O20:
[12] a) A. G. Kolchinski, D. H. Busch, N. W. Alcock, J. Chem. Soc.
Chem. Commun. 1995, 1289–1291; b) P. R. Aston, P. T. Glink, J. F.
Stoddart, P. A. Tasker, A. J. P. White, D. J. Williams, Chem. Eur. J.
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Acknowledgements
This work was financially supported by the Grant-in-Aid for Scientific
Research from MEXT, Japan (Nos. 18064008 and 19655013). K.N. thanks
the Global COE Program (Education and Research Program for Materi-
al Innovation), MEXT, Japan for financial support.
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Received: April 15, 2010
Published online: October 13, 2010
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