Dynamic covalently bonded rotaxanes cross-linked by imine bonds between the axle and ring: Inverse temperature dependence of subunit mobility

Article abstract of DOI:10.1002/anie.200600750

(Figure Presented) Building bridges: Imine bridges between the axle and ring components in rotaxanes allow simple rotaxane synthesis and a novel method for motion control to be developed. The submolecular mobility in this rotaxane-type assembly is regulated by the imine-bond formation/cleavage (see scheme). The relative abundance of the [2]rotaxane increases with decreasing temperature under dynamic equilibrium conditions.

Full text of DOI:10.1002/anie.200600750

Angewandte
Chemie
Supramolecular Chemistry
DOI: 10.1002/anie.200600750
Dynamic Covalently Bonded Rotaxanes Cross-
Linked by Imine Bonds between the Axle and
Ring: Inverse Temperature Dependence of
Subunit Mobility**
Hidetoshi Kawai,* Takeshi Umehara, Kenshu Fujiwara,
Takashi Tsuji,* and Takanori Suzuki
Establishing methods to control submolecular movements of
rotaxane components is a prerequisite for the development of
artificial devices that function through translational and
rotational motion at the molecular level. During the last
decade, many systems capable of controlling interactions
among components through external stimuli, such as metal
binding, change in pH value, electrochemistry, light, or
temperature, have been developed to realize on/off switching
[*] Dr. H. Kawai, T. Umehara, Prof. K. Fujiwara, Prof. T. Tsuji,
Prof. T. Suzuki
Division of Chemistry
Faculty of Science
Hokkaido University, Sapporo 060-0810 (Japan)
Fax: (+81)11-706-2714
E-mail: kawai@sci.hokudai.ac.jp
[**] We are grateful to K. Watanabe of the GC-MS and NMR Laboratory
(Hokkaido University) for the mass-spectrometric analyses and to
Dr. Y. Kumaki of the High-Resolution NMR Laboratory (Hokkaido
University) for the ROESY and variable-temperature NMR meas-
urements. This study was supported by JSPS KAKENHI (No.
16750024).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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of subunit mobility or change in the
position of the ring on the axle in rotaxanes
(molecular shuttles).[1]
The use of dynamic covalent bonds,[2]
which can be formed and broken reversibly
under mild conditions, to link components
seems promising for this purpose. There
are no precedents for the use of the imine
bond[3] as a cross-linkable/cleavable motif
between the axle and ring components of
rotaxanes,[4] yet we found it very useful for
constructing interlocked compounds able
to control the subunit mobility. The imine
compounds in general can be equilibrated
with the corresponding amine–aldehyde
pair under hydrolytic conditions. Accord-
ingly, the novel assembly can adopt the
imine-bridged rotaxane (strictly, [1]rotax-
ane[5]), in which the ring is covalently fixed
on the axle, or the [2]rotaxane, in which the
ring can freely move on the axle
(Scheme 1). Furthermore, the [2]rotaxane
Scheme 1. Dynamic formation of [2]rotaxanes 2 from imine-bridged rotaxanes 1 under
acidic hydrolysis/dehydration conditions, and the transformation of 2 into [2]rotaxane 3 by
dithioacetalization of the formyl groups.
Scheme 2. Synthesis of imine-bridged rotaxanes 1: a) 4-BrC6H4CH2CN, cat. PhCH2NEt3Cl, PhMe/40% NaOH, 658C (19 and 28% for (E)- and (Z)-
4a, respectively); b) 4-TBSOC6H4B(OH)2, [Pd(PPh3)4], PhH/EtOH/2m Na2CO3, 808C (98% for (E)-4b; 97% for 6a); c) DIBAL, PhH (for 5a) or
CH2Cl2 (for 5b), 258C (94% for 5a, 84% for 5b); d) TBAF, then Cs2CO3, propargyl bromide, THF, 258C (87%); e) Cu(OAc)2, CH3CN, 808C
(79%); f) H2, 10% Pd/C, THF, 258C (>99% for 7b; >99% for 1c); g) TFA, 4-Š ms, PhH, reflux (>99% for 1a; 95% for 1b); h) TBAF, then
Cs2CO3, 8a or 8b, THF/DMF, 258C (68% for 1d; 52% for 1e, 69% for 1 f). DIBAL=diisobutylaluminum hydride, TBAF=tetrabutylammonium
fluoride, TFA=trifluoroacetic acid, 4-Š ms=4-Š molecular sieves, DMF=dimethylformamide, TBS=tert-butyldimethylsilyl.
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2 generated by hydrolysis could be transformed to another
[2]rotaxane 3 by protection of the functional groups, thus
preventing its participation in the dynamic regeneration of
the imine-bridged rotaxane. In this way, we expected that the
independent mobility of the axle and ring components in this
novel type of rotaxane can be regulated based on the
controllable reversibility of the dynamic covalent bond.
Herein, we report the preparation of novel assembly 1 by
threading an axle bearing two formyl groups into a macro-
cyclic diamine, directed by cross-linking imine bond forma-
tion,[6] and attaching bulky end groups. We also report that
[2]rotaxane 2 is successfully generated in equilibrium with 1 in
an acidic medium, in which the relative abundance of 2
increases with decreasing temperature, and that 2 is trapped
by ethanedithiol to afford “nonequilibrating” [2]rotaxane 3.
The axle molecule 5 was designed by exploiting the well-
Figure 2. X-ray structure of imine-bridged pseudorotaxane 1a in a THF
solvate. Hydrogen atoms and solvents are omitted for clarity.
defined geometrical features of the hydrindacene (1,2,3,5,6,7-
[7]
hexahydro-s-indacene)skeleton.
The less-bulky carbalde-
5b into 7a quantitatively afforded 1b. Imine-bridged pseu-
dorotaxane 1c with its flexible macrocycle was quantitatively
obtained by hydrogenation of 1b over 10% Pd/C. Finally, end
groups were attached to 1b and 1c by one-pot desilylation–
benzylation reactions with 8a or 8b to afford imine-bridged
rotaxanes 1d, 1e, or 1 f (see Figure 3b and the Supporting
Information[9]).
hyde groups at the 2,6-positions preferentially occupy the
pseudoaxial positions, and so can work as linkers with the
amino groups of macrocycle 7 at opposing sides of the
molecular plane. The bromo-terminated dicarbaldehyde axle
5a and TBSO-terminated axle 5b were prepared from 1,2,4,5-
tetrakis(bromomethyl)benzene (Scheme 2). Macrocyclic di-
amine 7a was prepared from 2,6-diarylaniline 6a by oxidative
coupling.
Upon mixing equimolar amounts of 5a and macrocycle 7a
in CDCl3 at 298 K, the 1H NMR spectrum showed a new set of
resonances just after the addition of a catalytic amount of
TFA or silica gel. The newly generated species resonated at a
higher field than most of the protons of both components
(Figure 1). Signals that arose from 5a and 7a remained
detectable for several hours. However, the addition of 4-Š ms
to this sample or azeotropic refluxing in benzene led to the
quantitative formation of doubly bridged pseudorotaxane 1a.
Imine-bridged pseudorotaxane 1a was isolated intact by
column chromatography on alumina or gel-permeation chro-
matography (GPC). X-ray analysis of the THF solvate
unambiguously revealed the threading of the hydrindacene
axle through the macrocycle to create Ci-symmetric 1a
(Figure 2).[8] An imine-directed threading of a longer axle
Figure 3. 1H NMR spectra (300 MHz, CDCl3, 298 K) of a) axle 5e,
b) imine-bridged rotaxane 1 f, c) macrocycle 7b, d) dithioacetalized
[2]rotaxane 3 f, and e) dithioacetalized axle 5 f. The lettering corre-
spond to the assignments shown in Scheme 3.
With these imine-bridged rotaxanes in hand, we studied
the dynamic generation of the [2]rotaxanes 2 under acidic
hydrolysis conditions. The addition of TFA to a solution of 1a
or 1b in wet CHCl3 led to the quantitative (> 95%)formation
of the axle, 5a or 5b, and the macrocycle 7a. Similar
hydrolysis and dethreading was observed for 1d with 4-
[tris(4’-tert-butylphenyl)methyl]phenoxy
end
groups
(Scheme 3). These results obviously indicate the lability of
the imine bonds in 1 toward acidic hydrolysis and the ready
dethreading of the resultant pseudorotaxanes with the
insufficiently bulky end groups.
Figure 1. 1H NMR spectra (300 MHz, CDCl3) of a) hydrindacene axle
5a, b) imine-bridged pseudorotaxane 1a, and c) macrocycle 7a. The
lettering corresponds to the assignments shown in Scheme 2.
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Scheme 3. Generation of [2]rotaxanes 2 from the imine-bridged rotaxanes 1 by acidic hydrolysis and transformation to the “nonequilibrating”
[2]rotaxane 3.
In striking contrast, compound 1 f exhibited dynamic
and was consistent with the structure of the partially hydro-
lyzed monoimine 9 f, whereas the latter was simpler and in
good agreement with that expected for the desired [2]rotax-
ane 2 f (see the Supporting Information).[10] The upfield shifts
of the xylylene CH2 protons in 2 f, but not in 9 f, relative to 1 f
suggest relocation of the macrocycle toward the end group
from the central hydrindacene moiety. The observed temper-
ature dependence of the equilibrated ratios indicates that the
dynamic generation of 2 f and 9 f by hydrolysis of the imine
bonds are enthalpy-driven processes, whereas the reverse
behavior in its hydrolysis. Thus, a new set of resonances,
including a CHO signal at d = 9.4 ppm, appeared upon
addition of TFA to 1 f in CDCl3 at 298 K. Another set of
resonances was observed when the spectrum was recorded at
258 K, and interestingly both new sets of signals enhanced in
intensity at the expense of those from 1 f as the recording
temperature was lowered (see Figure 4 and the Supporting
Information). The scrutiny of those sets of spectra revealed
that the former spectrum was of a species low in symmetry
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resides around the tether groups and rapidly shuttles between
the two xylylene spacers, as in the case of [2]rotaxane 2 f.
In summary, by using diformylhydrindacene 5 as a
synthetic platform, we have demonstrated the validity of a
novel threading method directed by imine-bond formation.
From the resultant imine-bridged [2]rotaxane 1, two types of
[2]rotaxane 2 and 3 were generated through the imine-bond
cleavage, that is, acidic hydrolysis that leads to a dynamic
mixture containing 2 and thioacetalization of 2 to give 3 in
situ. More importantly, the submolecular mobility in this
novel assembly could be regulated by the imine-bond
formation/cleavage between the macrocycle and axle: the
imine-bond formation allows control over the ability of the
macrocycle to be able to move over the axle or not. This
restriction of motion must be important for “ratcheting”,[11]
a
crucial requirement for the preparation of molecular
machines that are more complex than simple switchable
molecular shuttles. Another outstanding feature of the
present system is the temperature dependence of a proportion
of 2 under the hydrolytic equilibration: as the temperature is
lowered, the proportion of 2 relative to 1 is increased.
Increasing submolecular mobility as a bulk with lowering of
temperature is unusual, and we are investigating the exploi-
tation of this peculiar behavior.
Figure 4. 1H NMR spectra (600 MHz, 0.08% TFA/CDCl3 (v/v)) of the
hydrolyzed mixture containing imine-bridged rotaxane 1 f, monoimine
9 f, and [2]rotaxane 2 f. An equilibrated ratio of 1 f/9 f/2 f is shown in
parenthesis at a) 313 K (81:18:ꢀ1), b) 293 K (72:24:4), c) 273 K
(64:30:6), d) 253 K (52:34:14), and e) 233 K (42:36:22). The lettering
corresponds to the assignments shown in Scheme 3.
Received: February 27, 2006
Published online: May 31, 2006
Keywords: entropy · imines · molecular dynamics · rotaxanes ·
.
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[8] X-ray crystal structural data for 1a·4THF (collected at 103 K):
¯
C90H82Br2N2O8, Mr = 1479.45, triclinic P1, a = 11.185(5), b =
12.645(3), c = 14.799(7)Š, a = 67.08(5), b = 82.55(6), g =
68.39(5)8, V= 8461.0(1)Š 3, 1calcd(Z=1) = 1.370 gcmÀ3
,
m =
1.196 cmÀ1, 7611 independent reflections (Rint = 0.131)and 509
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