Relative rotational motion between α-cyclodextrin derivatives and a stiff axle molecule

Article abstract of DOI:10.1021/jo702237q

(Figure Presented) Novel [2]rotaxanes bearing α-cyclodextrin (α-CD) derivatives and a diphenylacetylene axis molecule with trinitrobenzene as a bulky stopper have been prepared to investigate the relative rotary movement of a ring relative to an axis molecule and that of an axis molecule in a ring by NMR techniques. [2]Rotaxanes 2 and 3 were composed of α-CD derivatives (2: 6-phenyl-amide-α-CD; 3: 6-stilbene-amide- α-CD). The protons of α-CDs in rotaxanes were thoroughly assigned by the two-dimensional NMR techniques (TOCSY, COSY, ROESY, HMQC, and HMBC). The protons of α-CD in rotaxane 1 did not show splitting, whereas the resonance peak shifts and splitting for the corresponding protons of α-CD derivatives in rotaxanes 2 and 3 were observed by the shielding and deshielding effects from a diphenylacetylene axis molecule. The splitting of resonance peaks was closely related to the rotary movements of α-CDs and an axis molecule. We supposed that α-CD in rotaxane 1 rotates freely around a diphenylacetylene axis molecule, and vice versa, whereas the rotary movement of α-CD derivatives and the axis molecules of rotaxanes 2 and 3 were restricted by the steric repulsion between the substituent group of α-CD and the stopper group of an axis molecule. To estimate the relative rotary movement of CDs and an axis molecule in rotaxanes, the rotational correlation time (τ_c) of rotaxanes was measured by ¹³C NMR. The results indicate that the corresponding rotary movement of the modified α-CD and the axis molecules in rotaxanes 2 and 3 depends on the size of the substituent group.

Full text of DOI:10.1021/jo702237q

Relative Rotational Motion between r-Cyclodextrin Derivatives and
a Stiff Axle Molecule
Dai Nishimura, Tomoya Oshikiri, Yoshinori Takashima, Akihito Hashidzume,
Hiroyasu Yamaguchi, and Akira Harada*
Department of Macromolecular Science, Graduate School of Science, Osaka UniVersity, Toyonaka,
Osaka 560-0043, Japan
harada@chem.sci.osaka-u.ac.jp
ReceiVed October 16, 2007
Novel [2]rotaxanes bearing R-cyclodextrin (R-CD) derivatives and a diphenylacetylene axis molecule
with trinitrobenzene as a bulky stopper have been prepared to investigate the relative rotary movement
of a ring relative to an axis molecule and that of an axis molecule in a ring by NMR techniques. [2]-
Rotaxanes 2 and 3 were composed of R-CD derivatives (2: 6-phenyl-amide-R-CD; 3: 6-stilbene-amide-
R-CD). The protons of R-CDs in rotaxanes were thoroughly assigned by the two-dimensional NMR
techniques (TOCSY, COSY, ROESY, HMQC, and HMBC). The protons of R-CD in rotaxane 1 did not
show splitting, whereas the resonance peak shifts and splitting for the corresponding protons of R-CD
derivatives in rotaxanes 2 and 3 were observed by the shielding and deshielding effects from a
diphenylacetylene axis molecule. The splitting of resonance peaks was closely related to the rotary
movements of R-CDs and an axis molecule. We supposed that R-CD in rotaxane 1 rotates freely around
a diphenylacetylene axis molecule, and vice versa, whereas the rotary movement of R-CD derivatives
and the axis molecules of rotaxanes 2 and 3 were restricted by the steric repulsion between the substituent
group of R-CD and the stopper group of an axis molecule. To estimate the relative rotary movement of
CDs and an axis molecule in rotaxanes, the rotational correlation time (τc) of rotaxanes was measured by
13C NMR. The results indicate that the corresponding rotary movement of the modified R-CD and the
axis molecules in rotaxanes 2 and 3 depends on the size of the substituent group.
Introduction
good example of controlled molecular movement in both linear
and rotary molecular motor systems. Recently, excellent studies
Molecular motors in biological systems are roughly distin-
guished between linear molecular motors, such as myosin,
kinesin, dynein, etc.,1-4 and rotary motors, such as F0F1-ATP
synthase, F1-ATPase, etc.5-6 Rotaxanes are considered to be a
(1) Goodsell, D. S. Our Molecular Nature: The Body’s Motors, Machines
and Messages; Copernics: New York, 1996.
(2) Vale, R. D.; Milligan, R. A. Science 2000, 288, 88.
(3) Howard, J. Mechanics of Motor Proteins and the Cytoskelton; Sinauer
Associates: Sunderland, MA, 2001.
* Corresponding author. Telephone +81-6-6850-5445; fax +81-6-6850-5445.
10.1021/jo702237q CCC: $40.75 © 2008 American Chemical Society
Published on Web 03/13/2008
2496
J. Org. Chem. 2008, 73, 2496-2502

Motion between an R-CD and a Stiff Axle Molecule
on controlled synthetic linear7,8 and rotary molecular motors
have been reported by using rotaxane as building blocks, which
were achieved by controlling rotary movement.9-12 We previ-
ously reported that the linear movement of R-cyclodextrin (R-
CD) on pseudo-[2]rotaxane with dicationic axle molecules
showed controlled direction of faces of R-CD depending on the
axle terminal groups.13 In the present report, we have focused
on the rotary movement of R-CD derivatives around a diphe-
nylacetylene axle molecule in suitably designed rotaxanes. NMR
studies of CD rotors with an axle molecule were reported by
some research groups.14-18 Now we have investigated the
relationship between the structure of substituent groups in
modified CDs and the rotational motion of CDs and/or an axis
molecule. Three kinds of R-CD on [2]rotaxane have been
prepared (Figure 1). The effect of a substituent group of R-CD
on the rotary movement was investigated by variable temper-
ature NMR spectroscopy and the rotational correlation time (τc).
FIGURE 1. Chemical structures of R-CD-based rotaxanes.
Results and Discussion
Preparation of Rotaxanes and Crystal Structure of Ro-
taxane 1. [2]Rotaxanes (1, 2, and 3) were prepared by the
reaction of diaminodiphenylacetylene with sodium 2,4,6-trini-
trobenzene-1-sulfonate in aqueous solutions of CD derivatives
as outlined in Scheme 1. The crude products were subjected to
a reversed phase HPLC to give [2]rotaxanes (1, 2, and 3) in
(4) Frey, E. Chem. Phys. Chem. 2002, 3, 270.
(5) (a) Boyer, P. D. Biochim. Biophys. Acta 1993, 1440, 215. (b) Boyer,
P. D. Angew. Chem., Int. Ed. 1998, 37, 2296. (c) Walker, J. E. Angew.
Chem., Int. Ed. 1998, 37, 2308.
(6) (a) Elston, T.; Wang, H.; Oster, G. Nature 1998, 391, 510. (b) Oster,
G.; Wang, H. Biochim. Biophys. Acta 2000, 1458, 482.
FIGURE 2. Crystal structure of rotaxane 1. Carbon, oxygen, and
nitrogen are shown in gray, red, and purple, respectively.
SCHEME 1. Preparation of [2]Rotaxanes
(7) (a) Linke, M.; Chambron, J.-C.; Heitz, V.; Sauvage, J.-P.; Semetey,
V. Chem. Commun. 1998, 2469. (b) Blanco, M.-J.; Jimen´ez-Molero, M.
C.; Chambron, J.-C.; Heitz, V.; Linke, M.; Sauvage, J.-P. Chem. Soc. ReV.
1999, 28, 293-305. (c) Jimen´ez, M. C.; Dietrich-Buchecker, C.; Sauvage,
J.-P.; De Cian, A. Angew. Chem., Int. Ed. 2000, 39, 1295-1298. (d)
Jimen´ez-Molero, M. C.; Dietrich-Buchecker, C.; Sauvage, J.-P. A. Angew.
Chem., Int. Ed. 2000, 39, 3284-3287. (e) Jimen´ez-Molero, M. C.; Dietrich-
Buchecker, C.; Sauvage, J.-P. Chem. Eur. J. 2002, 8, 1456-1466. (f)
Dietrich-Buchecker, C.; Jimen´ez-Molero, M. C.; Sartor, V.; Sauvage, J.-P.
Pure Appl. Chem. 2003, 75, 1383-1393.
(8) Liu, Y.; Flood, A. H.; Bonvallet, P. A.; Vignon, S. A; Northrop, B.
H.; Tseng, H.-R.; Jeppesen, J. O.; Huang, Τ. J.; Brough, Β.; Baller, M.;
Magonov, S.; Solares, S. D.; Goddard, W. A.; Ho, H.-M.; Stoddart, J. F. J.
Am. Chem. Soc. 2005, 127, 9745-9759.
(9) Shukla, R.; Deetz, M. J.; Smith, B. D. Chem. Commun. 2000, 2397.
(10) (a) Koumura, N.; Zijlstra, R. W. J.; Delden, R. A. van; Harada, N.;
Feringa, B. L. Nature 1999, 401, 152. (b) Koumura, N.; Geertsema, E. M.;
Meetsma, A.; Feringa, B. L. J. Am. Chem. Soc. 2000, 122, 12005. (c)
Feringa, B. L. Acc. Chem. Res. 2001, 34, 504.
(11) (a) Kelly, T. R.; De Silva, H.; Silva, R. A. Nature 1999, 401, 150.
(b) Kelly, T. R.; Silva, R. A.; De Silva, H.; Jasmin, S.; Zhao, Y. J. Am.
Chem. Soc. 2000, 122, 6935. (c) Kelly, T. R. Acc. Chem. Res. 2001, 34,
514.
(12) (a) Leigh, D. A.; Wong, J. K. Y.; Dehez, F.; Zerbetto, F. Nature
2003, 424, 174. (b) Bottari, G.; Dehez, F.; Leigh, D. A.; Nash, P. J.; Perez,
E. M.; Wong, J. K. Y.; Zerbetto, F. Angew. Chem., Int. Ed. 2003, 42, 5886.
(c) Hannam, J. S.; Lacy, S. M.; Leigh, D. A.; Saiz, C. G.; Slawin, A. M.
Z.; Stitchell, S. G. Angew. Chem., Int. Ed. 2004, 43, 3260.
(13) (a) Oshikiri, T.; Takashima, Y.; Yamaguchi, H.; Harada, A. J. Am.
Chem. Soc. 2005, 127, 12186-12187. (b) Oshikiri, T.; Takashima, Y.;
Yamaguchi, H.; Harada, A. Chem. Eur. J. 2007, 13, 7091.
(14) Kuroda, Y.; Yamada, M.; Tabushi, I. J. Chem. Soc., Perkin Trans.
2 1989, 1409.
(15) Mantsch, H. H.; Saito, H.; Smith, I. C. P. Prog. Nucl. Magn. Reson.
Spectrosc. 1977, 11, 211.
(16) Behr, J. P.; Lehn, J.-M. J. Am. Chem. Soc. 1976, 98, 1743.
(17) Chen, W.-H.; Fukudome, M.; Yuan, D.-Q.; Fujioka, T.; Mihashi,
K.; Fujita, K. Chem. Commun. 2000, 541.
(18) Onagi, H.; Blake, C. J.; Easton, C. J.; Lincoln, S. F. Chem. Eur. J.
2003, 9, 5978.
65%, 67%, and 8% yield, respectively. The sodium adducts of
molecular ion of rotaxanes were observed by MALDI-TOF mass
spectroscopy. Pseudo-rotaxanes, which do not have end stoppers,
showed no such molecular ion peaks of pseudo-rotaxane because
of their dissociations. We have obtained a single crystal of
rotaxane 1 suitable for X-ray crystallography analysis (Figure
2). The crystal structure of rotaxane 1 shows that the wider rim
(secondary hydroxyl group side) of R-CD is located close to
the trinitrobenzene end group. The distance between secondary
hydroxyl groups of R-CD and the nitro group showed an average
of 2.95-3.85 Å, whereas the distance between primary hydroxyl
groups of R-CD and the nitro group showed an average of 3.85-
4.60 Å. These results indicate that we succeeded in obtaining
interlocked molecules, rotaxanes (1, 2, and 3).
J. Org. Chem, Vol. 73, No. 7, 2008 2497

Nishimura et al.
FIGURE 4. Results of the peak shifts of inner protons (C3H and C5H)
of modified R-CDs from 30 °C to -60 °C. (a and b) Protons of C3H
and C5H in rotaxane 2, respectively. (c and d) Protons of C3H and
C5H in rotaxane 3, respectively. A vertical scale (A-F) represents the
glucopyranose unit.
units of B, C, and E, whereas the downfield shifts of C3A,D
H
and C5AH peaks were observed as shown in Figure 4a,b. For
rotaxane 3, C3B,C,FH and C5B,C,E,FH peaks showed upfield shifts
at -60 °C. The downfield shifts of C3AH and C5A,FH peaks
with a decrease in temperature were caused by the deshielding
effect (Figure 4c,d). The glucopyranose units of A and D in
rotaxanes 2 and 3 are located adjacent to the edge of a
diphenylacetylene axis molecule at -60 °C. It should be noted
that the corresponding signals of rotaxane 3 showed larger peak
shifts and splitting than those of rotaxane 2 (Figure 4). Steric
repulsion between the substituent group of R-CD and the stopper
group (trinitrophenyl group) of an axis molecule is supposed
to restrict the rotary movement between modified R-CDs and
axis molecules.
ROESY Spectra of Rotaxanes Measured under Varying
Temperatures. The detailed conformations of rotaxanes 2 and
3 were determined by using ROESY NMR measurements. The
ROESY NMR spectra of rotaxanes 2 and 3 at 30 °C showed
correlation peaks between inner protons (C3H and C5H) of
modified R-CD and the protons (i and k) of the diphenylacety-
lene axis molecule (Figure 5a,c). For rotaxane 2, the correlation
peaks between C5H and k proton and between C3H and i proton
were observed. On the other hand, no correlation peak between
C5H and i proton was observed because rotaxanes form
asymmetric structures due to the bucket structure of R-CDs.
The correlation intensities between C5A-FH and k proton (or j
proton) and between C3A-FH and i (or j proton) proton showed
equivalent intensities at 30 °C, indicating that modified CDs
freely rotate around a diphenylacetylene axis molecule on the
NMR relaxation time scale (<10-3 s)19 at 30 °C. Rotaxane 3
showed similar inclusion and rotation behavior at 30 °C.
For rotaxane 2 at -60 °C, correlation peaks between
C3A,B,D,EH and i proton were observed, as well as those between
C5A,B,D,EH and k proton, whereas C3C,FH did not show the
correlation peaks with i proton, as well as between C5C,FH and
k proton. For rotaxane 3 at -60 °C, C3A,D,EH and C5D,EH of
6-stilbene-amide-R-CD were correlated with i and k protons of
FIGURE 3. 1H NMR spectra of rotaxanes 1 (a), 2 (b), and 3 (c) in
methanol-d4 (0.6 mM) under variable temperature. *: Exchange peak
between H2O and methanol-d4.
1H NMR Analyses of Rotaxanes. Temperature Variation.
1
The H NMR spectra of [2]rotaxanes 1, 2, and 3 at varying
temperatures are shown in Figure 3. The resonance peaks of
these rotaxanes have been thoroughly assigned by COSY,
TOCSY, HMQC, HMBC, and ROESY measurements. The C1H
protons of the glucopyranose unit of A-F in R-CD, hereinafter
called C1A-FH, in rotaxane 1 exhibited a peak shift downfield
with a decrease in temperature, whereas the corresponding
protons in rotaxane 1 did not split because R-CD is not modified
(Figure 3a). The C1A-FH peaks in rotaxanes 2 and 3 were split
by the introduction of a substituent group to R-CD and an
anisotropic effect from a diphenylacetylene axle molecule. The
C1AH and C1DH peaks in rotaxanes 2 and 3 shifted downfield
with decrease in temperature, respectively, whereas the C1BH,
C1CH, and C1FH peaks of rotaxanes 2 and 3 shifted upfield,
respectively (Figures 3b,c). Figure 4 summarizes the peak shifts
of the inner protons of modified R-CDs (C3H and C5H) for
rotaxanes 2 and 3 at 30 °C and -60 °C, respectively. For
rotaxane 2, C3B,C,FH and C5B,C,EH peaks showed the upfield
shifts with a decrease in temperature by the shielding effect
from a diphenylacetylene axis molecule on the glucopyranose
the axis molecule, respectively. Neither C3B,C,FH nor C5B,C,F
H
(19) Silverstein, R. M.; Webster, F. X. Spectrometric Identification of
Organic Compounds, 6th ed.; Wiley: New York, 1998.
2498 J. Org. Chem., Vol. 73, No. 7, 2008

Motion between an R-CD and a Stiff Axle Molecule
FIGURE 5. ROESY NMR spectra of rotaxanes 2 (a and b) and 3 (c and d) in methanol-d4 (5 mM) under variable temperature.
showed the correlation peaks with k proton. The distance
between C3A-FH and i proton and between C5A-FH and k
proton in rotaxane 1 was 2.698-4.643 Å and 2.575-3.928 Å,
respectively, which were measured with the data of single X-ray
analysis. These results indicate that the relative rotational
movements between modified R-CDs and axis molecules are
significantly decreased at -60 °C.20 The rotation behavior of
rotaxane 3 is different from that of rotaxane 2 as represented
schematically in Figure 6.
diphenylacetylene group and 13C of C1, C2, and C4 in R-CDs
by using 270, 400, 500, and 600 MHz NMR spectrometers,
respectively, corresponding to 67.77, 100.4, 125.5, and 150.6
MHz resonance frequencies for 13C, respectively (Table 1).
Figure 7 shows the relationship between the obtained T1 data
and the resonance frequency for rotaxane 1. Curve fitting was
performed on these plots by using eq 1 to determine a rotational
correlation time (τc) showing the molecular fluctuation (Table
2). The relative movements between R-CDs and axis molecules
were estimated by ∆(1/τc). τc of the axis molecules were shorter
than those of R-CDs in each rotaxane, indicating that the relative
rotation rates of axis molecules are faster than that of R-CDs.
The order of ∆(1/τc) is rotaxanes 1 > 2 = 3. The relative rotary
movements of CDs and/or axis molecules in rotaxanes 2 and 3
were restricted relative to that of rotaxane 1. There is a slight
difference in motion between rotaxanes 2 and 3. This result is
in excellent agreement with the 2D ROESY NMR experi-
ments.
Rotational Relaxation Time Measurement for [2]Rotax-
anes. Longitudinal relaxation times (T1) of 13C NMR for [2]-
21
rotaxanes were measured in DMSO-d6 at 30 °C to estimate
the average time scale for molecular motions of R-CDs. In the
observation of the motion of rotaxanes, it is necessary to
distinguish the motion of axis molecules and R-CD molecules.
We have measured the T1 for 13C of the 2′-position in a
(20) The torsion angle between phenyl rings of diphenlyacetylene was
8.68 Å in rotaxane 1, measured by single crystal X-ray analysis. However,
the diphenylacetylene did not show a disordered structure. If the nonspecific
glucopyranose units show the correlation peaks for the phenyl ring, the
phenyl ring should show a flip of more than 60o. On the basis of these
data, we supposed that the flipping phenyl rings did not occur during the
2D ROESY NMR measurement.
(21) We have to adjust the concentration of the solution to measure τc
by 13C NMR spectroscopy because these rotaxanes have high solubility
for DMSO-d6.
Conclusion
We have observed the rotary movement of R-CDs as a rotor
on the rotaxanes by NMR measurements. ROESY measurements
showed that R-CDs rotate around an axis molecule faster on
the NMR time scale at 30 °C; however, rotaxanes 2 and 3
J. Org. Chem, Vol. 73, No. 7, 2008 2499

Nishimura et al.
FIGURE 8. Schematic illustration of rotation behavior of [2]rotaxanes.
This figure shows a typical result, [2]rotaxane with 6-stilbene-amide-
R-CD.
of an axis molecule triggered the restriction of rotary movement
of the R-CDs around the axis molecule. Now we are preparing
novel [2]rotaxanes, without acceptor molecules (trinitrobenzene
group), to control the rotary movement by photoirradiation.
FIGURE 6. Schematic illustration of rotary movement of rotaxanes 2
and 3. The rotary movement of axis molecules were omitted to clarify
the rotation behavior of axis molecules and modified R-CDs.
Experimental Section
Longitudinal Relaxation Time Measurements. 13C NMR
measurements were performed to determine the longitudinal
relaxation time, T1, by using JEOL EX-270 (resonance frequency
for 13C: ωr ) 67.77 MHz), JEOL GSX-400 (resonance frequency
for 13C: ωr ) 100.4 MHz), JEOL Lambda-500 (resonance
frequency for 13C: ωr ) 125.5 MHz), and Varian Unity plus-600
(resonance frequency for 13C: ωr ) 150.6 MHz) spectrometers at
30 °C via a conventional inversion recovery pulse sequence, 90°-
τ-180°, under the deuterium lock mode. The rotational correlation
time, τc, for each 13C nucleus in the rotaxanes was determined via
eq 1 with obtained T1 values at different resonance frequencies.22
1
NT1
γH2γC2h2
µ0
τc
3τc
6τc
)
+
+
40π rCH 1+9(ωrτc)
1+(ωrτc)2 1+25(ωrτc)
2
6
2
2
(4π)
(
)
(1)
1
where N, µ0, gH, γC, h, and rCH are the number of Hs directly
bound to 13C, permeability of free space (4π × 10-7 H‚m-1),
gyromagnetic ration of 1H (2.675 × 108 rad‚T-1‚s-1), gyromagnetic
ratio of 13C (0.688 × 108 rad‚T-1‚s-1), Planck’s constant (6.626 ×
10-34 J‚s), and distance between H and 13C, respectively, 0.1102
1
FIGURE 7. Dependency of (NT1)-1 on ωr for C1, C2, and C5 nuclei
in rotaxane 1 in DMSO-d6 at 30 °C. See Figures S16 and S17 for
rotaxanes 2 and rotaxanes 3, respectively.
nm for a diphenlyacetylene group and 0.112 nm for C1-H, C2-H,
C4-H of the R-CDs. These distances were calculated by Spartan
‘04 using the Hartree-Fock method.
showed nonequivalent correlation peaks between the protons
of an axis molecule and inner protons of R-CDs, indicating that
the rotational motion of the R-CDs and the axis molecules are
slowed down at -60 °C. To estimate the significant difference
in rotary movement between rotaxans 2 and 3, we have
measured a rotational correlation time (τc) for an axis molecule
and R-CDs, respectively. Comparing rotaxanes 1, 2, and 3 on
the basis of an axis molecule, the rotational rates of modified
R-CDs in rotaxanes 2 and 3 were slower than that of the R-CD
in rotaxane 1 (Figure 8). We suppose that the steric hindrance
between the substituent group of the R-CDs and the end group
2500 J. Org. Chem., Vol. 73, No. 7, 2008

Motion between an R-CD and a Stiff Axle Molecule
TABLE 1. Dependency of Longitudinal Relaxation Time (T1) on 13C of the 2′-Position in a Diphenylacetylene Group and 13C of C1, C2, and
C4 in r-CDs in [2]Rotaxanes (1, 2, and 3) by Using 67.77, 100.4, 125.5, and 150.6 MHz in Resonance Frequencies for 13C
T1 of rotaxane 1, s
T1 of rotaxane 2, s
T1 of rotaxane 3, s
CD unit
CD unit
CD unit
resonance
frequency, MHz
axis
C1
C2
C4
axis
C1
C2
C4
axis
C1
C2
C4
67.77
100.4
125.5
150.6
0.16
0.22
0.23
0.23
0.12
0.21
0.24
0.30
0.12
0.19
0.25
0.30
0.12
0.18
0.24
0.29
0.15
0.21
0.24
0.24
0.13
0.18
0.27
0.30
0.13
0.21
0.26
0.30
0.14
0.20
0.25
0.29
0.15
0.19
0.22
0.25
0.10
0.21
0.26
0.35
0.12
0.19
0.26
0.35
0.12
0.19
0.26
0.33
a Concentration of rotaxanes: rotaxane 1; 20.4 mM, rotaxane 2; 20.6 mM, rotaxane 3; 20.6 mM.
TABLE 2. Rotational Correlation Time (τc) of Axis Molecules and
r-CD in DMSO-d6
stilbene), 7.63 (d, J ) 7.1 Hz, 2H, 2′-H of stilbene), 7.44-7.27
(m, 5H, 3′,4′-H of stilbene, olefin of stilbene). TLC (ethyl acetate/
hexane 1:1): Rf ) 0.30 (relative to the solvent front). IR (KBr), ν
axis
CD
3300-2500 (O-H), 1680 (CdO), 1425 (O-H), 1290 (C-O) cm-1
.
τc,
1/τc,
τc,
1/τc,
FAB-MS, m/z, 224 (M+), 207, 178, 154, 135, 107. Mp. 254-255
°C. Anal. Calcd for C15H12O2‚0.35H2O: C, 78.14; H, 5.55.
Found: C, 78.05; H, 5.22.
10-10 (s)
108 (s-1
)
10-10 (s)
108 (s-1
)
∆1/τc
rotaxane 1
rotaxane 2
rotaxane 3
5.0
5.5
6.0
20
18
17
15
14
18
6.8
7.3
5.7
13
11
11
∆1/τc ) 1/τc (axis) - 1/τc(CD)
Preparation of 6-Phenyl-amide-R-CD. Benzoic acid (52.4 mg,
0.429 mmol), dicyclohexyl carbodiimide (DCC; 126 mg, 0.612
mmol), and 1-hydroxybenzotriazole (HOBt; 95.4 mg, 0.622 mmol)
were added to dried DMF (10 mL) at 0 °C. After 1 h, a solution of
6-NH2-R-CD (374.1 mg, 0.379 mmol) in dried DMF (20 mL) was
added to the reaction mixture, and the mixture was stirred at 0 °C
for 2 h. It was allowed to warm to room temperature and stirred
for 5 days. The mixture was poured into acetone (1 L). The
precipitate was collected and dissolved in water. The solution was
applied to a DIAION HP-20 column. The column was flushed with
water (2 L) and then eluted with a water/methanol ) 20/80 (v/v).
The fraction was concentrated under reduced pressure, and pure
6-phenyl-amide-R-CD was obtained (white powder, 348 mg,
(b) Preparation of 6-Stilbene-amide-R-CD. 6-Stilbene-amide-R-
CD was prepared by the same method as 6-phenylamide-R-CD,
using 4-stilbene carboxylic acid (224 mg, 1.00 mmol), DCC (248
mg, 1.20 mmo), HOBt (184 mg, 1.20 mmol), and 6-NH2-R-CD
(987 mg, 1.00 mmol). 6-Stilbene-amide-R-CD was obtained (white
powder, 664 mg, 56.3%). 1H NMR (270 MHz, DMSO-d6) δH 8.31
(t, J ) 5.8 Hz, 1H, amido), 7.83 (d, J ) 8.3 Hz, 2H, 3-H of
stilbene), 7.66 (d, J ) 8.4 Hz, 2H, 2-H of stilbene), 7.63 (d, J )
7.1 Hz, 2H, 2′-H of stilbene), 7.42-7.26 (m, 5H, 3′,4′-H, olefin of
stilbene), 5.58-5.38 (m, 12H, O2,3H of CD), 4.94-4.74 (m, 6H,
C1H of CD), 4.59-4.34 (m, 5H, O6H of CD), 3.84-3.21 (m,
overlaps with HOD, others of CD). TLC (n-butanol/ethanol/water
5:4:3): Rf ) 0.58 (relative to the solvent front). MALDI TOF-
MS, m/z (%), 1200.7 (100) [M + Na]+, 1177.3 (24) [M]+, 1217.4
(15) [M + K]+. Mp 284-286 °C (decomp). Anal. Calcd for
C51H71O30N‚0.3DMF‚4.35H2O: C, 48.76; H, 6.45; N, 1.48.
Found: C, 48.76; H, 6.44; N, 1.47.
1
85.4%). H NMR (500 MHz, DMSO-d6) δH 8.32 (t, J ) 5.8 Hz,
1H, amido), 7.80 (d, J ) 7.2 Hz, 2H, ortho H of phenyl), 7.51 (t,
J ) 7.4 Hz, 1H, p-Ph), 7.43 (t, J ) 7.4 Hz, 2H, m-Ph), 5.57-5.36
(m, 12H, O2,3H of CD), 4.93-4.73 (m, 6H, C1H of CD), 4.56-
4.34 (m, 5H, O6H of CD), 3.83-3.22 (m, overlaps with HOD,
others of CD). TLC (n-butanol/ethanol/water 5:4:3): Rf ) 0.56
(relative to the solvent front). MALDI TOF-MS, m/z (%), 1098.5-
(100) [M + Na]+, 1114.0(55) [M + K]+. Mp 285-286 °C
(decomp). Anal. Calcd for C43H65O30N‚7.73H2O: C, 42.50; H, 6.67;
N, 1.15; Found: C, 42.37; H, 6.48; N, 1.35.
Preparation of 6-Stilbene-amide-R-CD. (a) Preparation of
4-Stilbenecarboxylic Acid. Styrene (1.56 g, 14.9 mmol) and
4-iodobenzoic acid (3.97 g, 15.9 mmol) were dissolved in tetrahy-
drofran (THF; 17 mL) and triethylamine (20 mL). The solution
was refluxed in the presence of triphenylphosphine (0.124 g, 0.473
mmol) and palladium(II) acetate (0.100 g, 0.445 mmol) for 24 h.
After the removal of the solvent, ethyl acetate (150 mL) was added,
and the soluble part was washed with three portions of water (60
mL). The organic layer was concentrated under reduced pressure,
and recrystallization from hexane and ethyl acetate afforded pure
4-stilbenecarboxylic acid (pale brown powder, 472 mg, 14.1%).
1H NMR (270 MHz, DMSO-d6) δH 12.8 (br, 1H, OH), 7.92 (d, J
) 8.5 Hz, 2H, 3-H of stilbene), 7.71 (d, J ) 8.4 Hz, 2H, 2-H of
Preparation of 4,4′-Diaminodiphenylacetylene. PdCl2(PPh3)2
(35.9 mg, 0.0511 mmol), CuI (19.5 mg, 0.102 mmol), and
p-iodoaniline (1.10 g, 5.02 mmol) were dissolved in THF (30 mL)
at room temperature under an argon atmosphere. p-Ethynylaniline
(589 mg, 5.03mmol) was added, and a 0.5 M solution of aqueous
ammonia (20 mL) was added dropwise. The mixture was stirred
for 4 h at room temperature and extracted with diethyl ether (3 ×
50 mL). The organic layer was concentrated under reduced pressure.
Ethyl acetate (150 mL) was added to the residue, and the soluble
(22) Lyerla, J. R., Jr.; Levy, G. C. Topics in Carbon-13 NMR Spectros-
copy; Levy, G. C., Ed.; Wiley: New York, 1974; Vol. 1, pp 79-148.
J. Org. Chem, Vol. 73, No. 7, 2008 2501

Nishimura et al.
part was poured into hexane (1 L). The precipitate was collected
3, 2′-H of diphenylacetylene and m-Ph), 7.04 (d, J ) 8.6 Hz, 2H,
3′-H of diphenylacetylene), 5.02-4.90 (m, 6H, C1A∼FH of CD),
4.14-3.37 (m, 30H, others of CD). TLC (n-butanol/ethanol/water
5:4:3): Rf ) 0.76 (relative to the solvent front). MALDI TOF-
MS, m/z (%), 1683.9 (100) [M + Na - 3N or O]+, 1668.3 (95)
[M + Na - 4N or O]+, 1653.9 (75) [M + Na - 5N or O]+, 1697.6
(75) [M + Na - 2N or O]+, 1635.2 (50) [M + Na - 6N or O]+,
1715.9 (50) [M + Na - N or O]+. Mp: 278-279 °C (decomp).
Anal. Calcd for C69H79O42N9‚5.74H2O: C, 44.23; H, 4.87; N, 6.73;
Found: C, 44.46; H, 5.10; N, 6.73.
and washed with hexane to afford pure 4,4′-diaminodiphenylacety-
1
lene (pale brown powder, 420 mg, 40.1%). H NMR (500 MHz,
DMSO-d6) δH 7.09 (d, J ) 8.5 Hz, 4H, 2,2′-position of phenyl),
6.51 (d, J ) 8.5 Hz, 4H, 3,3′-H of Ph), 5.37 (s, 4H, amino). TLC
(ethyl acetate/hexane 1:1): Rf ) 0.38 (relative to the solvent front).
Mp 208-210 °C. Anal. Calcd for C14H12N2‚0.35H2O: C, 78.37;
H, 5.97; N, 13.06; Found: C, 78.46; H, 5.61; N, 12.70.
Preparation of [2]Rotaxanes. Rotaxane 1. R-CD (972 mg, 1.00
mmol) and sodium hydrogen carbonate (NaHCO3; 394 mg, 4.69
mmol) were dissolved in water (20 mL). 4,4′-Diaminodipheny-
lacetylene (42.3 mg, 0.203 mmol) was added to the mixture and
stirred at room temperature. After 48 h, 2,4,6-trinitrobenzenesulfonic
acid sodium salt dehydrate (TNBS; 143 mg, 0.406 mmol) was added
to the mixture and stirred for 48 h at room temperature. The resultant
solution was washed with ethyl acetate (5 × 25 mL) and
concentrated under reduced pressure. The residue was dissolved
in water, and the solution was applied to a DIAION HP-20 column
(eluted with water/methanol ) 100/0 to 70/30). The rotaxane 1
was obtained when the column was eluted with 30-70% methanol
(orange powder; 210 mg, 64.6%). 1H NMR (500 MHz, methanol-
d4) δH 9.15 (s, 2H, 3-H and 3′-H trinitrophenyl), 9.07 (s, 2H, 3-H
and 3′-H trinitrophenyl), 8.02 (d, J ) 8.5 Hz, 2H, 2-H of
diphenylacetylene), 7.41 (d, J ) 8.5 Hz, 2H, 2′-H of dipheny-
lacetylene), 7.32 (d, J ) 8.5 Hz, 2H, 3-H of diphenylacetylene),
7.23 (d, J ) 8.5 Hz, 2H, 3′-H of diphenylacetylene), 4.91 (d, J )
3.5 Hz, 6H, C1H of CD), 4.03 (dt, J ) 2.2, 9.1 Hz, 6H, C5H of
CD), 3.85 (dd, J ) 3.1, 12 Hz, 6H, C6HB of CD), 3.80 (t, J ) 9.3
Hz, 6H, C3H of CD), 3.67 (dd, J ) 1.9, 12 Hz, 6H, C6HA of CD),
3.57 (t, J ) 9.2 Hz, 6H, C4H of CD), 3.44 (dd, J ) 3.3, 9.8 Hz,
6H, C2H of CD). TLC (n-butanol/ethanol/water 5:4:3): Rf ) 0.65
(relative to the solvent front). MALDI TOF-MS, m/z (%), 1609.6
(100) [M + Li]+, 1595.6 (82) [M + Li - N or O]+, 1579.6 (52)
[M + Li - 2N or O]+, 1563.6 (30) [M + Li - 3N or O]+, 1625.6
(28) [M + Na]+, 1547.6 (16) [M + Li - 4N or O]+. Mp: 296-
297 °C (decomp). Anal. Calcd for C62H74O42N8‚8.03H2O: C, 42.60;
H, 5.19; N, 6.41; Found: C, 42.37; H, 4.96; N, 6.34.
(c) Rotaxane 3. Rotaxane 3 was prepared by the same method
as that used for rotaxane 1 except for the purification method, using
6-stilbene-R-CD (252 mg, 0.214 mmol), NaHCO3 (168 mg, 14.1
mmol), water (22 mL), 4,4′-diaminodiphenylacetylene (29.4 mg,
0.141 mmol), and TNBS (103 mg, 0.293 mmol). The crude product
was dissolved in water and subjected to reversed phase preparative
HPLC. Fractions containing the rotaxane 3 were concentrated under
reduced pressure, and pure rotaxane 3 was obtained (red powder,
1
19.7 mg, 7.72%). H NMR (500 MHz, methanol-d4) δH 9.12 (s,
2H, 3-H and 3′-H trinitrophenyl), 8.91 (s, 2H, 3-H and 3′-H
trinitrophenyl H), 8.03 (d, J ) 8.5 Hz, 2H, 2-H of diphenylacety-
lene), 7.72 (d, J ) 8.5 Hz, 2H, 3-H of stilbene), 7.54 (d, J ) 8.4
Hz, 2H, 2-H of stilbene), 7.51 (d, J ) 7.3 Hz, 2H, 2′-H of stilbene),
7.36-7.25 (m, 7H, 3′, 4′-H of stilbene and 3, 2′-H of dipheny-
lacetylene), 7.17 (d, J ) 16 Hz, 1H, olefin of stilbene), 7.10 (d, J
) 16 Hz, 1H, olefin of stilbene), 6.90 (d, J ) 8.6 Hz, 2H, 3′-H of
diphenylacetylene), 5.02-4.89 (m, 6H, C1A-FH of CD), 4.16-3.36-
(m, 30H, others of CD). TLC (n-butanol/ethanol/water 5:4:3): Rf
) 0.71 (relative to the solvent front). MALDI TOF-MS, m/z (%),
1795.7 (100) [M - N]+, 1780.2 (90) [M - 2N or O]+, 1810.7
(50) [M]+, 1764.8 (40) [M - 3N or O]+, 1833.5 (18) [M + Na]+.
Mp: 290-292 °C (decomp). Anal. Calcd for C77H85O42N9‚
7.74H2O: C, 47.48; H, 5.19; N, 6.47; Found: C, 47.45; H, 5.13;
N, 6.39.
Acknowledgment. The authors thank Mr. S. Adachi from
the Graduate School of Science, Osaka University, for NMR
experiments and fruitful discussion. We are grateful to M. Shiro
and M. Yamazaki (Rigaku Corporation, Japan) for measuring
the single X-ray structure. This work has been supported by
“Stress and Symbiosis on Supramolecules” program of the
Ministry of Education, Culture, Sports, Science and Technology,
Japan.
(b) Rotaxane 2. Rotaxane 2 was prepared by the same method
as that used for rotaxane 1 except for the method of purification,
using 6-Phe-R-CD (156 mg, 0.145 mmol), NaHCO3 (255 mg, 3.03
mmol), water (30 mL), 4,4′-diaminodiphenylacetylene (30.1 mg,
0.145 mmol), and TNBS (107 mg, 0.304 mmol). The crude product
was dissolved in water, and the solution was applied to a DIAION
HP-20 column (eluted with water/methanol ) 100/0 to 80/20). The
rotaxane 2 was obtained when the column was eluted with 80%
Supporting Information Available: Selected NMR data (1D
NMR and ROESY spectrum). The determination of association
constants and the diffusion coefficients are shown. This material
is available free of charge via the Internet at http://pubs.acs.org.
1
methanol (orange powder, 164 mg, 66.5%). H NMR (500 MHz,
methanol-d4) δH 9.15 (s, 2H, 3-H and 3′-H trinitrophenyl H), 9.04
(s, 2H, 3-H and 3′-H trinitrophenyl H), 8.03 (d, J ) 8.6 Hz, 2H,
2-H position of diphenylacetylene), 7.69 (d, J ) 7.1 Hz, 2H, ortho
H of phenyl), 7.45 (t, J ) 7.5 Hz, 1H, p-Ph), 7.39-7.32 (m, 6H,
JO702237Q
2502 J. Org. Chem., Vol. 73, No. 7, 2008