A rotaxane synthesis based on stilbene photoisomerization. A photoswitchable catch and release process

Article abstract of DOI:10.1039/b306349f

A [2]rotaxane, having (Z)-α-methylstilbene as a stopper, is (1) synthesized in good yield by using a (E)- to (Z)-stilbene photoisomerization process, and (2) dissociated by reverse photoisomerization from (Z)- to (E)-stilbene.

Full text of DOI:10.1039/b306349f

A rotaxane synthesis based on stilbene photoisomerization. A
photoswitchable catch and release process†
Yuji Tokunaga,*a Koichiro Akasaka,a Kenji Hisada,b Youji Shimomuraa and Suzuka Kakuchia
a Department of Materials Science and Engineering, Faculty of Engineering, Fukui University, Fukui,
910-8507, Japan. E-mail: tokunaga@matse.fukui-u.ac.jp
b Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Fukui, 910-8507, Japan
Received (in Cambridge, UK) 9th June 2003, Accepted 22nd July 2003
First published as an Advance Article on the web 31st July 2003
A [2]rotaxane, having (Z)-a-methylstilbene as a stopper, is
(1) synthesized in good yield by using a (E)- to (Z)-stilbene
photoisomerization process, and (2) dissociated by reverse
photoisomerization from (Z)- to (E)-stilbene.
The design of rotaxanes organized by noncovalent interactions
has attracted much attention.1 Photoresponsive rotaxanes are
highly attractive interlocked molecules because of the fact that
their properties can be changed in response to photo-irradiation.
Photoinduced dynamics and electron transfer between wheel
and axle groups in rotaxanes have been previously investi-
gated,2 and applications of these properties to material science
have been developed.3
Scheme 1 Reagents and conditions: (i) MeLi; (ii) Ph3PNCHPh; (iii) H3O+;
(iv) 4-tert-butylbenzylamine; (v) NaBH4; (vi) H3O+ then NH4PF6.
The structure of a rotaxane can be rigidly fixed by the
placement of bulky functionality at the axle ends to prevent
slippage.4 In this case, the association–dissociation process
between the two components is generally not reversible.5 An
important application of rotaxanes is found in the work of Yui
and co-workers,6 which has led to the development of
biodegradable polyrotaxanes for biomedical applications (e.g.,
drug carriers). In these rotaxanes, degradation processes
promote the release of biologically active compounds.
The reversible isomerizations of (E) and (Z)-stilbene can be
promoted by using UV irradiation.7 The (E)-stilbene isomer has
a planar conformation whereas its (Z)-isomer exists in a
conformation in which the two cis-benzene rings twisted owing
to a repulsive interaction between protons at the 2 and 2A
positions in the planar structure. Owing to this feature, we
believed that (Z)-stilbenes would serve as effective stoppers in
the construction of rigid rotaxanes. Inspection of molecular
models of (Z)- and (E)-a-methylstilbenes as well as dibenzo-
24-crown-8 (DB24C8) (Fig. 1) shows that the flat (E)-isomer
can be easily threaded through the crown. In contrast, the
twisted (Z)-isomer is sufficiently large to prevent being
threaded through DB24C8.8 Based on these and other con-
siderations, we developed a novel approach to rotaxane
synthesis, which relies on the use of (1) hydrogen bonding
guided self-assembly between secondary ammonium groups
and DB24C8,9 and (2) photoisomerization of (Z)- and (E)-a-
methylstilbene as a reversible end-closing–end-opening proc-
ess.
the corresponding methylketone (Scheme 1). Wittig olefination
of the ketone followed by deprotection produces a separable
mixture of (E)- and (Z)-stilbene derivatives 2. Individual
treatment of these isomers with 4-tert-butylbenzylamine gives
the corresponding imines, which are then converted to the
corresponding ammonium salts, (E)- and (Z)-3. Reduction and
counter ion exchange then generates substances which possess
(E)- and (Z)-a-methylstilbene groupings on one end of the chain
and a bulky aryl group9b at the other end.
1H NMR spectroscopy was employed to monitor the
complexation of the isomeric ammonium salts to DB24C8. The
1H NMR (1 : 1 CDCl3–CD3CN) spectrum of a mixture of (E)-3
and DB24C8 revealed the formation of the pseudorotaxane (E)-
4. In contrast, a pseudorotaxane was not produced when (Z)-3
and DB24C8 were mixed. We next explored the proposed
photoisomerization approach to the synthesis of rotaxane. UV
irradiation of a 1 : 1 CDCl3–CD3CN solution of (E)-3 (272 mM)
and DB24C8 (408 mM), using benzil7b (272 mM) as a
sensitizer, led to efficient E to Z-stilbene isomerization of the
pseudorotaxane (Scheme 2) and formation of a rotaxane (Z)-4 in
a 73% yield (87%: NMR yield) after purification. This
substance was stable in d6-DMSO at room temperature in the
dark.10 Rotaxane forming photoisomerization reactions pro-
moted by 9-fluorenone, duroquinone, and pyrene gave the
rotaxane in 54% (79%: NMR), 71% (79%: NMR), and 58%
(77%: NMR) yields, respectively. The rotaxane was charac-
terized by 1H and 13C NMR, FAB mass, and IR spectrometric
methods. As expected,9 the 1H NMR spectrum of this substance
contained proton resonances (assigned using COSY and
ROESY methods) with higher field chemical shifts than those
of the crown ether and low field chemical shifts for the benzylic
protons of the axle. The presence of an intense peak at m/z 818,
corresponding to the loss of the counter ion, in the FAB mass
spectrum confirmed the structural assignment of the rotaxane.
1H NMR spectroscopy was used to monitor the progress of
the photochemical isomerization reaction resulting in the
The group that serves as a precursor to the axle in this
rotaxane synthetic design is the stilbene containing ammonium
salt (E)-3. The route used to prepare 3 is initiated by methylation
of the dimethylacetal of 4-carboxybenzaldehyde, which affords
Fig. 1 Space-filling models of (Z)-a-methylstilbene (a), (E)-a-methyl-
stilbene (b), and dibenzo-24-crown-8 (c).
† Electronic supplementary information (ESI) available: NMR spectra. See
http://www.rsc.org/suppdata/cc/b3/b306349f/
Scheme 2
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formation of the rotaxane. A solution containing equimolar (23
mM) quantities of (E)-3, DB24C8, and benzil in 1 : 1 CDCl3–
CD3CN was irradiated at 0 °C. The time course of the
appearance and disappearance of resonances, assigned to (Z)-4
(Z)-4 leads to (E)-3 and this is followed by the conversion of
(E)-3 to (Z)-3 (Fig. 3).12
The observations described above show that (E,Z)-photo-
isomerization of the stilbene component of the pseudorotaxane
can be used to form a rotaxane. This approach avoids use of
bulky functionality that is more typically employed to cap the
ends of the axle grouping. In addition, the results demonstrate
that stilbene photoisomerization can also be used to promote
degradation of the rotaxane.
We thank Professor Isa of this University and Professor
Anzai and Dr Hoshi of Tohoku University for making
spectroscopic measurements.
1
and (Z)-3, and those of (E)-4 and (E)-3 was determined by H
NMR integration. During the course of the reaction, the signals
of the protons of the (E)-isomers decreased in intensity
concomitant with the increases in the intensities of the
resonances associated with the (Z)-isomers (Fig. 2). Based on
these results, the association constant of pseudorotaxane (E)-4
was determined to be 900 ± 110 M21 11,12
.
Notes and references
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Fig. 2 Plots of concentrations of (E)-3, (Z)-3, (E)-4 and (Z)-4 vs. time during
irradiation of a 1 : 1 CDCl3–CD3CN solution of (E)-3 and DB24C8 in the
presence of benzil at 0 °C. The photoreaction was carried out in an NMR
tube under nitrogen with light from a super-high pressure mercury lamp
(Ushio USH-250W).
We next examined the endo-opening reaction of rotaxane (Z)-
4. Irradiation of a solution of (Z)-4 and benzophenone7b in d6-
DMSO led to the production of (E)-3, (Z)-3, and DB24C8. 1H
NMR monitoring of this process revealed that photodegradation
of (Z)-4 fits a first-order curve, and that photodegradation of
4 An alternative method based on electrostatic trap was reported by
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10 The rotaxane is not stable at high temperature in d6-DMSO owing to the
disruption of hydrogen bonding interactions. The first-order rate
constant for dissociation was found to be 5.8 3 1027 s21 in d6-DMSO
at 90 °C (t1/2 of 332 h).
Fig. 3 Plots of concentrations of (E)-3, (Z)-3, and (Z)-4 vs. time during
irradiation of a d6-DMSO solution of (Z)-4 in the presence of benzophenone
at room temperature. The photoreaction was carried out in an NMR tube
under nitrogen with light from a super-high pressure mercury lamp (Ushio
USH-250W).
11 Resonances for an unidentified compound were observed in the 1H
NMR spectrum after prolonged irradiation. The association constant
was measured at 25 °C.
12 See electronic supplementary information.
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