Efficient syntheses of bis(m-phenylene)-26-crown-8-based cryptand/paraquat derivative [2]rotaxanes by immediate solvent evaporation method

Article abstract of DOI:10.1016/j.tet.2008.11.081

A novel bis(m-phenylene)-26-crown-8-based cryptand has been synthesized. It has been used to prepare two 1:1 complexes with two paraquat derivatives with high association constants (6.5×10⁵ and 4.0×10⁵ M^-1) in acetone. In

Full text of DOI:10.1016/j.tet.2008.11.081

Tetrahedron 65 (2009) 1488–1494
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient syntheses of bis(m-phenylene)-26-crown-8-based cryptand/paraquat
derivative [2]rotaxanes by immediate solvent evaporation method
Feng Wang a, Qizhong Zhou a, Kelong Zhu a, Shijun Li a, Chong Wang a, Ming Liu a, Ning Li a,
,
Frank R. Fronczek b, Feihe Huang a
*
a Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
b Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel bis(m-phenylene)-26-crown-8-based cryptand has been synthesized. It has been used to prepare
two 1:1 complexes with two paraquat derivatives with high association constants (6.5ꢀ105 and
4.0ꢀ105 Mꢁ1) in acetone. In the solid state the cryptand forms a 2:1 threaded structure with paraquat
and an interesting supramolecular poly[2]pseudorotaxane threaded structure with a dihydroxyethyl-
substituted paraquat derivative, respectively. It has been further used to prepare cryptand/paraquat
derivative [2]rotaxanes efficiently by the immediate solvent evaporation method using easily available
3,5-dimethylphenyl groups as the stoppers.
Received 23 September 2008
Received in revised form 18 November 2008
Accepted 26 November 2008
Available online 30 November 2008
Keywords:
Crown ether
Paraquat
Ó 2008 Elsevier Ltd. All rights reserved.
Host–guest system
Cryptand
Rotaxane
1. Introduction
efficient fabrication of mechanically interlocked structures is nec-
essary for their future applications in nanoscience and nanotech-
Non-covalent interactions are universal and important in bi-
ological systems, which motivated chemists to take advantage of
them to elegantly prepare complicated supramolecular architec-
tures,1 including interlocked threaded structures2 and supramo-
lecular polymers.3 These supramolecular architectures have been
widely used in nanoscience and nanotechnology.4
Paraquat derivatives (N,N0-dialkyl-4,40-bipyridinium salts) have
been widely used to prepare threaded structures with crown
ether,5 bicyclic (cryptand),6 and tricyclic hosts.3c,7 Usually pseu-
dorotaxanes are intermediates to prepare interlocked threaded
structures, thus higher stabilities or association constants of
pseudorotaxanes will lead to higher yields in the fabrication of
interlocked threaded structures. It has been proved that crown
ether-based cryptands can form pseudorotaxanes with paraquat
derivatives and bind them much more strongly than the corre-
sponding simple crown ethers.6 However, so far mechanically
interlocked structures based on the cryptand/paraquat derivative
recognition motif are still rare. Only examples are two [2]rotaxanes,
for which bis(m-phenylene)-32-crown-10-based cryptands served
as the macrocycles, recently reported by us.8 Considering that the
nology and to further explore the cryptand/paraquat derivative
recognition motif in the preparation of mechanically interlocked
structures, we prepared a novel bis(m-phenylene)-26-crown-8-
based cryptand 1, studied its complexations with paraquat de-
rivatives 2 and 3, and further used it in the efficient syntheses of
cryptand/paraquat derivative [2]rotaxanes using easily available
3,5-dimethylphenyl groups as the stoppers. Moreover, here the
immediate solvent evaporation method (ISEM)9 was adopted to
prepare the [2]rotaxanes, considering that ISEM can significantly
accelerate organic reactions compared to the conventional solution
conditions without any decrease in the yield. The results of these
studies are reported here.
2. Results and discussion
2.1. Synthesis of bis(m-phenylene)-26-crown-8-based 2,6-
pyridino-cryptand 1
The diester 4,10 prepared from the cyclization reaction between
methyl
3,5-bis(2-(2-(2-chloroethoxy)ethoxy)ethoxy)benzoate
and methyl 3,5-dihydroxybenzoate, was reduced with LiAlH4
to the corresponding bis(m-phenylene)-26-crown-8 diol 5, which
further reacted with pyridine-2,6-dicarbonyl chloride using
the pseudo-high dilution technique11 to afford bis(m-phenylene)-
* Corresponding author. Tel.: þ86 571 87953189; fax: þ86 571 87951895.
E-mail address: fhuang@zju.edu.cn (F. Huang).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.081

F. Wang et al. / Tetrahedron 65 (2009) 1488–1494
1489
Hα
Hγ
Hβ
O
O
O
O
O
H4
H6
H9
H7
PF6
H8
PF6
N
H3
N
H5
O
O
2
O
O
O
H10
PF6
N
PF6
H11
N
OH
N
H13
O
O
H2
HO
1
H12
3
H1
O
O
O
O
O
O
O
O
O
O
O
O
HO
LiAlH4, THF
58%
H3CO
O
O
OH
OCH3
O
O
O
O
5
4
O
O
O
O
O
O
O
O
N
Cl
Cl
O
O
O
O
CH2Cl2, Py, r.t.
45%
N
O
O
1
Scheme 1. Synthesis of bis(m-phenylene)-26-crown-8-based 2,6-pyridino-cryptand 1 from bis(m-phenylene)-26-crown-8 diester 4.
26-crown-8-based 2,6-pyridino-cryptand 1 in 45% yield, as shown
in Scheme 1. The host 1 was characterized by 1H NMR, 13C NMR, and
HRESIMS.
based cryptand (Ka¼6.5ꢀ105 Mꢁ1 in acetone) while the bis-
(m-phenylene)-26-crown-8-based cryptand is better than the
dibenzo-24-crown-8-based cryptand (Ka¼1.2ꢀ105 Mꢁ1 in aceto-
ne).6f In view of the fact that all these three cryptands have the
same third chain, the large difference in Ka values could probably
be attributed to the more aliphatic ethyleneoxy oxygen atoms,
efficient hydrogen bond acceptors, that the bis(m-phenylene)-32-
crown-10-based cryptand has than the other two cryptand
analogs. The reason for us to use a bis(m-phenylene)-26-crown-
8-based cryptand instead of a bis(m-phenylene)-32-crown-10-
based cryptand as the macrocycle to make [2]rotaxanes here is
that the cavity of the bis(m-phenylene)-26-crown-8-based
cryptand is smaller than that of the corresponding bis(m-phe-
nylene)-32-crown-10-based cryptand and appropriate stoppers
are more easily available.
2.2. The determination of stoichiometries of the
complexations between host 1 and either of guests 2 and 3
Then the complexations between 1 and either of 2 and 3 were
studied. When equimolar (2.00 mM) acetone solutions of cryptand
1 and either of paraquat derivative salts 2 and 3 were made, a bright
yellow color appeared as a result of charge-transfer interactions
between electron-rich aromatic rings of the cryptand host and
electron-poor pyridinium rings of the paraquat derivative guest.
Job plots12 (Fig. 1) based on UV–vis absorption spectroscopy data of
the charge-transfer band (
1 with 2 or 3 were of 1:1 stoichiometry in solution.
l
¼370 nm) proved that the complexes of
2.4. The 1H NMR study of the complexation of host 1 with
either of guests 2 and 3
2.3. Determination of association constants of 1$2 and 1$3
Then association constants (Ka) of complexes 1$2 and 1$3
were determined by probing the charge-transfer band of the
complexes by UV–vis spectroscopy and employing a titration
method. Progressive addition of an acetone solution with high
guest 2 or 3 concentration and low host 1 concentration to an
acetone solution with the same host 1 concentration resulted in
an increase of the intensity of the charge-transfer band of the
complex. Treatment of the collected absorbance data at
To further investigate the complexations between 1 and either
of 2 and 3, proton NMR spectra of equimolar (4.00 mM) acetone-d6
solutions of 1 with either of 2 and 3 were examined (Fig. 2). Both of
the two complexation systems 1$2 and 1$3 are fast exchange on the
proton NMR time scale. The chemical shift changes of protons on
cryptand host 1 showed some similar characteristics after com-
plexation with 2 and 3. Significant upfield shifts were observed for
aromatic protons H4 and H5. Pyridyl protons H1 and H2,
eneoxy protons Hb, and -ethyleneoxy protons Hg had downfield
shifts while benzyl protons H3 and -ethyleneoxy protons Ha
b-ethyl-
l
¼370 nm with a non-linear curve-fitting program afforded the
g
corresponding Ka values: 6.5 (ꢂ1.8)ꢀ105 Mꢁ1 for 1$2 and 4.0
(ꢂ0.7)ꢀ105 Mꢁ1 for 1$3.13 Comparison of the Ka value of 1$2 with
previously reported Ka values of complexes based on analogous
bis(m-phenylene)-32-crown-10- and dibenzo-24-crown-8-based
pyridyl ester cryptands with paraquat 2 indicated that the bis-
(m-phenylene)-32-crown-10-based cryptand (Ka¼5.0ꢀ106 Mꢁ1 in
acetone)6d is better for 2 than the bis(m-phenylene)-26-crown-8-
a
moved upfield. Pyridinium protons H6, H7, H9, and H10 of 2 and 3
and methyl protons H8 of 2 moved upfield while methylene protons
H12 and hydroxyl protons H13 of 3 moved downfield after com-
plexation of 1 with 2 and 3. N-Methylene protons H11 of 3 did not
have an obvious chemical shift change. Moreover, the appearance
of broad signals for the complexation system 1$3 in the 1H NMR

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F. Wang et al. / Tetrahedron 65 (2009) 1488–1494
2.5. Electrospray ionization mass spectrometry
(a)
0.6
0.4
0.2
0.0
The electrospray ionization mass spectrometry characterization
was done on solutions of 1 with either of 2 and 3. Peaks were found
at m/z 970.0 (100%) and 1030.1 (100%) for complexes 1$2 and 1$3,
respectively, corresponding to [1$2ꢁPF6]þ and [1$3ꢁPF6]þ. More-
over, a peak was found at m/z 732.5 (59%) corresponding to 2:1
complex 1$2$1. However, no peaks corresponding to other stoi-
chiometries were found in complexations of 1 with either of 2
and 3.
2.6. Crystal structures of complexes 1$2 and 1$3
Single crystals suitable for X-ray crystallography were obtained
by vapor diffusion of diisopropyl ether into solutions of 1 with ei-
ther of 2 and 3 in CH3CN. Cryptand 1 and paraquat 2 formed a 2:1
complex in the solid state (Fig. 3), which is not consistent with their
1:1 complexation stoichiometry in solution. The 2:1 complex 1$2$1,
0.0
0.2
0.4
0.6
0.8
1.0
[2]0/([2]0+[1]0)
(b)
a
pseudorotaxane-like [3]complex, is stabilized by hydrogen
bonding and face-to-face -stacking interactions between the ar-
omatic rings of 1 and the pyridinium rings of 2. Previously it was
reported that different bis(m-phenylene)-26-crown-8-based
0.6
0.4
0.2
0.0
p
a
cryptand with a tri(ethylene glycol) third chain can also form a 2:1
complex with 2 in the solid state as confirmed by single crystal
X-ray analysis.6c Similar to that complex, here none of N-methyl
hydrogens of 2 are involved in hydrogen bonding between the host
and guest in 1$2$1 either, and four b-pyridinium hydrogens of 2
form four hydrogen bonds (d and g in Fig. 3) with four ethyleneoxy
oxygen atoms of the host too. Here the two cryptand host mole-
cules of 1$2$1 are also connected by two hydrogen bonds (h in
Fig. 3). However, there are some differences due to the structure
difference of the two cryptand hosts. In the previous complex four
a
-pyridinium hydrogens of 2 form six hydrogen bonds directly with
0.0
0.2
0.4
0.6
0.8
1.0
the ethyleneoxy oxygen atoms of the cryptand host.6c In 1$2$1 two
[3]0/([3]0+[1]0)
water molecules serve as hydrogen bonding bridges and two
Figure 1. Job plots showing the 1:1 stoichiometries of the complexes between 1 and 2
(a) and 1 and 3 (b) in acetone by plotting the absorbance intensity at
host–guest charge-transfer band) against the mole fraction of the guest. [1]0, [2]0, and
[3]0 are initial concentrations of 1, 2, and 3. [1]0þ[2]0¼[1]0þ[3]0¼1.00 mM.
a-pyridinium hydrogens of 2 are indirectly connected to the host by
l
¼370 nm (the
six hydrogen bonds (a, b, and c in Fig. 3) while the other two
spectrum (Fig. 2d) suggested that the exchange rates during the
complexation and decomplexation processes were slow on the 1H
NMR spectroscopic time scale, which could result from the rela-
tively longer b-hydroxyethyl substitution groups of compound 3,
compared with the methyl substitution groups of compound 2.6f
H8
H6
H7
(a)
(b)
ethylene
protons
Hβ
Hγ
H4
H3
H2
Hα
H1
H5
(c)
(d)
ethylene
protons
Figure 3. A ball-stick view of the X-ray structure of 1$2$1. 1 is red, 2 is blue and water
moleculesꢁare magenta. Hydrogens are magenta, oxygens are green, and nitrogens are
black. PF6 counterions, other solvent molecules and hydrogens except the ones on 2
or involved in hydrogen bonding were omitted for clarity. Hydrogen bond parameters:
H/O (N) distance (Å), C(O)–H/O (N) angle (deg), C(O)/O (N) distance (Å) a, 2.12, 156,
3.16; b, 2.53, 135, 3.32; c, 2.42, 173, 3.37; d, 2.51, 143, 3.32; e, 2.48, 158, 3.38; f, 2.43, 132,
H9
H11
H10
H12
H13
(e)
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5
3.14; g, 2.64, 150, 3.49; h, 2.32, 173, 3.27. Face-to-face p-stacking parameters: centroid–
Figure 2. Partial 1H NMR spectra (500 MHz, acetone-d6, 295 K) of (a) paraquat 2, (b)
4.00 mM cryptand 1 and 2, (c) cryptand 1, (d) 4.00 mM cryptand 1 and 3, and (e)
paraquat derivative 3.
centroid distances (Å) 3.42, 3.94; ring plane/ring plane inclinations (deg): 0.7, 7.4. The
centroid–centroid distance (Å) and dihedral angle (deg) between the two pyridinium
rings of 2: 4.29, 0.3.

F. Wang et al. / Tetrahedron 65 (2009) 1488–1494
1491
ꢁ
Figure 4. A ball-stick view of the X-ray packing structure of 1$3. 1 is red, 3 is blue, hydrogens are magenta, oxygens are green, and nitrogens are black. PF6 counterions, solvent
molecules and hydrogens except the ones on 3 were omitted and only three [2]pseudorotaxanes are shown here for clarity. Hydrogen bond parameters: H/O (N) distance (Å),
C–H/O (N) angle (deg), C/O (N) distance (Å) i, 2.60, 150, 3.50; j, 2.38, 162, 3.35; k, 2.42, 152, 3.34; l, 2.35, 134, 3.13; m, 2.56, 159, 3.52; n, 2.70, 125, 3.37; o, 2.47, 122, 3.13; p, 2.35,
148, 3.24; q, 2.46, 124, 3.13. Face-to-face
p-stacking parameters: centroid–centroid distances (Å) 3.62, 3.77; ring plane/ring plane inclinations (deg): 11.1, 1.6. The centroid–centroid
distance (Å) and dihedral angle (deg) between the two pyridinium rings of 3: 4.28, 19.0.
a
-pyridinium hydrogens are directly connected to the host by four
contacts between reactants,9 here we used it to prepare two
cryptand/paraquat derivative [2]rotaxanes based on acylation re-
actions (the urethane formation as well as the esterification re-
actions) (Scheme 2).
hydrogen bonds (e and f in Fig. 3).
The crystal structure of 1$3 (Fig. 4) revealed its expected
[2]pseudorotaxane binding geometry. Just like 1$2$1, 1$3 is also
stabilized by hydrogen bonding and face-to-face
p
-stacking in-
Mixing 1 (0.019 mmol), 3 (0.017 mmol), 3,5-dimethylphenyl
isocyanate (0.102 mmol), and catalytic amount of dibutyltin dilau-
rate (DBTDL) in anhydrous acetonitrile (0.4 mL) followed by evap-
oration afforded a film, which further stood for 2 h at ambient
temperature. It was observed on the TLC plate that compound 3
was completely converted while only a slight amount of dumbbell
compound 7 was formed. Purification by flash column chroma-
tography afforded [2]rotaxane 6 in 81% yield. By contrast, the re-
action proceeding in the solution was also conducted using
threading-followed-by-stoppering method. Stirring the reaction
mixture at room temperature for 2 days followed by column
chromatography afforded [2]rotaxane 6 in 83% yield. It clearly
showed that reaction was accelerated by ISEM. Moreover, when
using 3,5-dimethylbenzoic anhydride as the stopper and catalytic
amount of trimethylphosphine as the base, [2]rotaxane 8 was
prepared in 85% yield with ISEM (Scheme 2). Hence, cryptand/
paraquat derivative rotaxanes could be efficiently prepared with
ISEM due to the strong binding between 1 and 3.
Partial proton NMR spectra of dumbbell-shaped components 7
and 9, [2]rotaxanes 6 and 8 as well as the cryptand 1 in acetone-d6
are shown in Figure 5. Chemical shift changes were found for all
protons of 1 and dumbbell-shaped compounds after the formation
of rotaxanes (Fig. 5). These chemical shift changes persisted even in
DMSO (Figs. S27 and S28), proving that 6 and 8 are rotaxanes since
no complexation is expected in this highly polar solvent.14 Fur-
thermore, protons of 7 and 9 were all split into two sets (Fig. 5),
further confirming that the threading of paraquat derivatives into
the cavity of cryptand 1 is unsymmetrical. The successful prepa-
ration of rotaxanes 6 and 8 proved that easily accessible 3,5-
dimethylphenyl group is big enough to serve as stoppers for
rotaxanes with cryptand 1 as the macrocycle and acylation re-
actions are applicable stoppering methods for preparing rotaxanes
by ISEM.
teractions in the solid state (Fig. 4). In the previously reported
crystal structure of a complex of 3 with a dibenzo-24-crown-8-
based pyridyl ester cryptand,6f paraquat derivative guest 3 is
symmetrically threaded into the cavity of the cryptand host and
none of its eight ethylene hydrogens are involved in hydrogen
bonding between the host and guest while here 3 is threaded
unsymmetrically into the cavity of bis(m-phenylene)-26-crown-8-
based cryptand host 1 and two of its eight ethylene hydrogens
are involved in hydrogen bonding (i and j in Fig. 4) between the
host and guest. In the above crystal structure of 1$2$1 all eight
pyridinium hydrogens are involved in hydrogen bonding between
the host and guest (Fig. 4), here only one
-pyridinium hydrogens are involved in hydrogen bonding (k, l,
m, n, and o in Fig. 4) between the host and guest. Only one of the
two pyridinium rings of 3 is involved in face-to-face -stacking
a-pyridinium and two
b
p
interactions with the two phenylene rings of 1 (Fig. 4). The di-
hedral angle between the two pyridinium rings of 3 is 19.0ꢃ
(Fig. 4). This twist presumably results from the maximization of
hydrogen bonding interactions between 1 and 3 as well as
minimization of the steric repulsion between the adjacent hy-
drogens on 3. Interestingly, an ester carbonyl oxygen atom of
cryptand host 1 forms two hydrogen bonds (p and q in Fig. 4)
with one a-pyridinium hydrogen and one N-ethylene hydrogen of
the paraquat derivative guest 3 in the neighboring [2]pseudor-
otaxane and [2]pseudorotaxanes are arranged linearly to form
a
supramolecualr poly[2]pseudorotaxane threaded structure
(Fig. 4).
2.7. Preparation of [2]rotaxanes by ISEM
Considering ISEM can accelerate organic reactions significantly
because the remarkable enhancement of molecule-to-molecule

1492
F. Wang et al. / Tetrahedron 65 (2009) 1488–1494
O
O
O
O
O
O
O
N
H
O
N O
O
N
N
H
N
O
NCO
DBTDL, ISEM
81%
2PF6
O
O
O
O
O
6
1
+
3
O
O
O
O
O
O
O
O
O
O
O
O
O
N
O
N
N
O
PMe3, ISEM
85%
O
O
O
O
2PF6
21
20
8
O
17
N
H
O
19
N
N
HO
OH
18
H
N
16
O
N
N
14
15
acetone, reflux
87%
2PF6
O
O
3
7
NCO
O
2PF6
28
22
23
25
O
O
N
N
Br
Br
N
N
HO
O
OH
26
27
24
O
DCC, DMAP
93%
DMF
22%
2PF6
O
10
9
Scheme 2. Synthesis of two bis(m-phenylene)-26-crown-8-based cryptand/paraquat derivative [2]rotaxanes and their corresponding dumbbell-shaped compounds.
stimulate further studies on cryptand/paraquat derivative func-
tional threaded structures.
H21
H19
H14
H15
H18
H20
H16 H17
(a)
H O
4. Experimental section
4.1. General
HDO
2
ethylene protons
(b)
(c)
H
β Hγ
Hα
H3
H4
Methyl 3,5-dihydroxybenzoate and tri(ethylene glycol)di-
chloride were reagent grade and used as received. Solvents were
either employed as purchased or dried according to procedures
described in the literature. NMR spectra were recorded on a Bruker
Advance DMX 500 spectrophotometer or a Bruker Advance DMX
400 spectrophotometer using the deuterated solvent as the lock
and the residual solvent or TMS as the internal reference. Low-
resolution electrospray ionization mass spectra were recorded on
a Bruker Esruire 3000 Plus spectrometer. High-resolution mass
spectrometry experiments were performed on a Bruker Daltonics
Apex III spectrometer.
H2
H5
H1
ethylene protons
(d)
H28
H22
H26
H23
H24
(e)
H25
H27
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5
Figure 5. Partial 1H NMR spectra (400 MHz, acetone-d6, 295 K) of (a) dumbbell
component 7, (b) rotaxane 6, (c) cryptand 1, (d) rotaxane 8, (e) dumbbell component 9.
4.2. Bis(m-phenylene)-26-crown-8-based 2,6-pyridino-
3. Conclusion
cryptand (1)
In summary, we have reported here that the novel bis(m-phe-
nylene)-26-crown-8-based cryptand 1 is a highly efficient host for
the complexation of paraquat derivatives. Consequently, this
cryptand was used to efficiently prepare cryptand/paraquat de-
rivative [2]rotaxanes by ISEM, for which easily available 3,5-
dimethylphenyl groups served as the stoppers and acylation
reactions are applicable methods. ISEM could accelerate the re-
action of preparing [2]rotaxanes obviously. The present results may
Pyridine (0.20 mL) was added to the solution of SOCl2 (7.50 mL,
100 mmol) and pyridine-2,6-dicarboxylic acid (3.34 g, 20 mmol).
The mixture was stirred at room temperature for 10 h. The solvent
was removed with a rotary evaporator to afford pyridine-2,6-
dicarbonyl dichloride as a white solid (2.98 g), which was collected
for the next step without further purification. To a solution of bis(5-
hydroxymethyl-m-phenylene)-26-crown-8 5 (1.00 g, 1.97 mmol) in
dichloromethane (800 mL) at 0 ꢃC under an atmosphere of nitrogen

F. Wang et al. / Tetrahedron 65 (2009) 1488–1494
1493
was added pyridine (0.32 g, 4.00 mmol). A solution of 2,6-pyr-
idinedicarbonyl dichloride (0.42 g, 2.07 mmol) in dichloromethane
(20 mL) was slowly added dropwise over 3 h while keeping the
solution at 0 ꢃC. The solution was then allowed to warm to room
temperature and stirred for 7 days before being concentrated in
vacuo. The resulting mixture was dissolved in chloroform (60 mL)
and washed with 2 M HCl and brine. The organic layer was evap-
orated to dryness using a rotary evaporator producing a yellow oil
residue. Purification of the residue by flash column chromatogra-
phy (dichloromethane/ethyl acetate, 6:1 v/v) afforded 1 as a white
solid (0.57 g, 45%). Mp 174–176 ꢃC. 1H NMR (400 MHz, acetone-d6,
67.4, 67.3, 67.1, 63.2, 63.1, 61.5, 60.1, 20.6, 20.5. HRESIMS: m/z calcd
for [MꢁPF6]þ C65H73F6N5O16P, 1324.4694, found 1324.4639, error
4.2 ppm.
4.4. Dumbbell-shaped component 7
Paraquat diol 3 (0.268 g, 0.50 mmol) and 3,5-dimethylphenyl
isocyanate (0.176 g, 1.20 mmol) were dissolved in acetone (15 mL)
and heated at reflux for 20 h. It was then cooled to room temper-
ature. Removal of acetone afforded a pale yellow solid, which was
washed with dichloromethane and acetonitrile to yield 7 as a white
solid (0.36 g, 87%). Mp 235–237 ꢃC. 1H NMR (400 MHz, acetone-d6,
room temperature)
d
(ppm): 8.30 (d, J¼8.0 Hz, 2H), 8.18 (t, J¼8.0 Hz,
1H), 6.57 (s, 4H), 6.45 (s, 2H), 5.23 (s, 4H), 4.00 (s, 4H), 3.93 (s, 4H),
room temperature)
d
(ppm): 9.43 (d, J¼6.8 Hz, 4H), 8.79 (d,
3.65 (br s, 8H), 3.56 (s, 8H). 13C NMR (125 MHz, acetone-d6/chlo-
J¼6.8 Hz, 4H), 8.47 (s, 2H), 7.02 (s, 4H), 6.63 (s, 2H), 5.26 (t, J¼4.4 Hz,
4H), 4.76 (t, J¼4.4 Hz, 4H), 2.16 (s, 12H). LRESIMS: m/z 685.0
[MꢁPF6]þ (100%), 539.0 [MꢁPF6ꢁHPF6]þ (44%). HRESIMS: m/z
calcd for [MꢁPF6]þ C32H36F6N4O4P, 685.2378, found 685.2352, er-
ror 3.8 ppm.
roform-d (1/1, v/v), room temperature)
d (ppm): 165.1, 160.1, 148.3,
138.5, 136.7, 128.4, 107.1, 102.3, 71.2, 69.9, 68.2, 67.4. HRESIMS: m/z
calcd for [MþH]þ C33H38NO12, 640.2394, found 640.2396, error
0.3 ppm.
4.3. Rotaxane 6
4.5. Rotaxane 8
4.3.1. By the immediate solvent evaporation method
A mixture of bis(m-phenylene)-26-crown-8-based cryptand 1
(12.0 mg, 0.019 mmol), paraquat diol 3 (9.2 mg, 0.017 mmol), 3,5-
dimethylbenzoic anhydride (19.4 mg, 0.069 mmol), and catalytic
amount of trimethylphosphine (Me3P, 0.26 mg) was dissolved in
acetonitrile (0.4 mL). The resulting yellow solution was evaporated
in vacuo, whereupon a film developed on the surface of the flask.
After 5 min, the evaporation was stopped and the film was left
standing in the open air at ambient temperature for 2 h. The mix-
ture was dissolved in acetonitrile and purified by flash column
chromatography (CH2Cl2/MeOH/MeNO2 15:1:1 v/v/v) to yield
rotaxane 8 as a yellow film (20.7 mg, 85%). 1H NMR (400 MHz, ac-
A mixture of bis(m-phenylene)-26-crown-8-based cryptand 1
(12.0 mg, 0.019 mmol), paraquat diol 3 (9.2 mg, 0.017 mmol), 3,5-
dimethylphenyl isocyanate (15.0 mg, 0.102 mmol), and catalytic
amount of dibutyltin dilaurate (DBTDL, 1.5 mg) was dissolved in
acetonitrile (0.4 mL). The resulting yellow solution was evaporated
in vacuo, whereupon a film developed on the surface of the flask.
After 5 min, the evaporation was stopped and the film was left
standing in the open air at ambient temperature for 2 h. The mix-
ture was dissolved in acetonitrile and H2O. A saturated aqueous
solution of NH4PF6 was added to the reaction mixture. On removal
of acetonitrile, a yellow precipitate was formed, which was filtered
off and dried in vacuo to afford the crude product, which was pu-
rified by flash column chromatography (CH2Cl2/MeOH/CH3NO2,
30:1:1 v/v/v) to yield rotaxane 6 as a yellow film (20.3 mg, 81%).
etone-d6, room temperature)
d
(ppm): 9.41 (d, J¼6.4 Hz, 2H), 9.04
(d, J¼6.4 Hz, 2H), 8.89 (d, J¼6.4 Hz, 2H), 8.39 (d, J¼8.0 Hz, 2H), 8.30
(t, J¼8.0 Hz, 1H), 8.24 (br s, 2H), 7.75 (s, 2H), 7.57 (s, 2H), 7.29 (s, 1H),
7.21 (s, 1H), 6.42 (s, 2H), 5.51 (s, 2H), 5.47 (d, J¼11.2 Hz, 2H), 5.43 (br
s, 2H), 5.15 (br s, 4H), 5.07 (br s, 2H), 4.90 (br s, 2H), 4.15 (d,
J¼11.2 Hz, 2H), 3.18–4.22 (m, 24H), 2.32 (s, 6H), 2.20 (s, 6H). 1H NMR
4.3.2. By the reaction in solution
A mixture of bis(m-phenylene)-26-crown-8-based cryptand 1
(12.0 mg, 0.019 mmol), paraquat diol 3 (9.2 mg, 0.017 mmol), 3,5-
dimethylphenyl isocyanate (15.0 mg, 0.102 mmol), and catalytic
amount of dibutyltin dilaurate (DBTDL, 1.5 mg) was dissolved in
anhydrous acetonitrile (5.0 mL). The mixture was stirred at room
temperature for 2 days. Then it was dissolved in acetonitrile and
H2O. A saturated aqueous solution of NH4PF6 was added to the
reaction mixture. On removal of acetonitrile, a yellow precipitate
was formed, which was filtered off and dried in vacuo to afford the
crude product, which was purified by flash column chromatogra-
phy (CH2Cl2/MeOH/CH3NO2, 30:1:1 v/v/v) to yield 6 as a yellow film
(20.7 mg, 83%). 1H NMR (400 MHz, acetone-d6, room temperature)
(400 MHz, DMSO-d6, room temperature) d (ppm): 9.33 (br s, 2H),
8.93 (br s, 2H), 8.67 (d, J¼5.6 Hz, 2H), 8.48 (d, J¼8.0 Hz, 2H), 8.36 (t,
J¼8.0 Hz, 1H), 7.95 (br s, 2H), 7.77 (s, 2H), 7.57 (s, 2H), 7.38 (s, 1H),
7.30 (s, 1H), 6.37 (s, 2H), 5.39–5.42 (m, 4H), 5.29 (br s, 2H), 5.09 (s,
2H), 5.04 (br s, 2H), 4.99 (br s, 2H), 4.84 (br s, 2H), 3.06–4.22 (m,
26H), 2.38 (s, 6H), 2.67 (s, 6H). 13C NMR (100 MHz, acetone-d6,
room temperature)
d (ppm): 166.3, 165.7, 164.7, 159.9, 158.3, 148.6,
147.4, 146.0, 145.4, 145.2, 139.3, 138.6, 138.5, 137.2, 135.3, 135.2,
129.4, 129.0, 128.9, 127.2, 125.9, 109.9, 104.5, 100.9, 70.7, 70.4, 69.8,
69.7, 67.3, 67.2, 66.9, 63.4, 63.1, 60.9, 59.6, 20.3, 20.2. LRESIMS: m/z
574.9 [Mꢁ2PF6]2þ (100%). HRESIMS: m/z calcd for [Mꢁ2PF6]2þ
C65H71N3O16, 574.7417, found 574.7429, error 2.1 ppm.
d
(ppm): 9.37 (d, J¼6.4 Hz, 2H), 9.08 (d, J¼6.4 Hz, 2H), 8.97 (d,
J¼6.4 Hz, 2H), 8.72 (br, 2H), 8.47 (d, J¼8.0 Hz, 2H), 8.35 (d, J¼8.0 Hz,
1H), 8.32 (d, J¼6.4 Hz, 2H), 7.14 (s, 2H), 7.02 (s, 2H), 6.68 (s, 1H), 6.58
(s, 1H), 6.47 (s, 2H), 5.66 (s, 2H), 5.54 (d, J¼11.6 Hz, 2H), 5.35 (br s,
4H), 5.05 (br s, 2H), 4.95 (br s, 2H), 4.77 (br s, 2H), 4.33 (d, J¼11.6 Hz,
2H), 3.41–4.28 (m, 24H), 2.20 (s, 6H), 2.08 (s, 6H). 1H NMR
4.6. Dumbbell-shaped component 9
A solution of 3,5-dimethylbenzoic acid (1.65 g, 11.0 mmol), DCC
(2.37 g, 11.5 mmol), and DMAP (0.49 g, 4.00 mmol) in dichloro-
methane (30 mL) was stirred for 1 h at room temperature, to which
was added 2-bromoethanol (1.25 g,10.0 mmol) in dichloromethane
(10 mL). The reaction mixture was stirred for 48 h at room tem-
perature, filtered, and concentrated to give a pale yellow oil, which
was purified by flash column chromatography (petroleum ether/
ethyl acetate, 30:1 v/v) to provide 2-bromoethyl 3,5-dime-
thylbenzoate 10 as a colorless oil (2.38 g, 93%). 1H NMR (400 MHz,
(400 MHz, DMSO-d6, room temperature)
d (ppm): 9.85 (br s, 1H),
9.67 (br s, 1H), 9.25 (d, J¼6.4 Hz, 2H), 8.78 (d, J¼6.4 Hz, 2H), 8.72 (d,
J¼6.4 Hz, 2H), 8.51 (d, J¼8.0 Hz, 2H), 8.38 (t, J¼8.0 Hz, 1H), 7.10 (s,
2H), 6.95 (s, 2H), 6.67 (s, 1H), 6.58 (s, 1H), 6.38 (s, 2H), 5.52 (s, 2H),
5.43 (d, J¼11.6 Hz, 2H), 5.27 (s, 2H), 5.22 (br s, 2H), 4.95 (br s, 2H),
4.82 (br s, 2H), 4.66 (br s, 2H), 4.24 (d, J¼11.6 Hz, 2H), 3.40–4.21 (m,
24H), 2.21 (s, 6H), 2.08 (s, 6H). 13C NMR (125 MHz, acetone-d6, room
chloroform-d, room temperature) d (ppm): 7.68 (s, 2H), 7.21 (s, 1H),
temperature)
d
(ppm): 164.9, 160.0, 158.4, 152.9, 148.8, 147.4, 146.0,
4.61 (t, J¼6.4 Hz, 2H), 3.64 (t, J¼6.4 Hz, 2H), 2.37 (s, 6H). HRESIMS:
m/z calcd for [MþH]þ C11H14BrO2, 257.0177, found 257.0168, error
3.5 ppm. A solution of 2-bromoethyl 3,5-dimethylbenzoate (2.38 g,
145.5, 145.2, 139.4, 138.6, 138.5, 138.4, 138.1, 137.2, 129.1, 125.9,
125.0, 124.8, 116.8, 116.2, 110.1, 104.6, 101.2, 70.8, 70.5, 69.9, 69.8,

1494
F. Wang et al. / Tetrahedron 65 (2009) 1488–1494
9.30 mmol) and 4,40-bipyridyl (0.48 g, 3.10 mmol) in dry DMF
(30 mL) was stirred at 60 ꢃC for 40 h. The resulting precipitate was
filtered. The crude yellow solid was then dissolved in deionized
water and an aqueous NH4PF6 solution was added to precipitate the
corresponding salt, which was further purified by flash column
chromatography (MeOH/2 M NH4Cl/MeNO2 20:2:1 v/v/v) to pro-
vide 9 as a white solid (0.56 g, 22%). Mp 241–243 ꢃC. 1H NMR
References and notes
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E. R.; Mendoza, S. M.; Bruno, C.; Marcaccio, M.; Wiering, P. G.; Paolucci, F.; Rudolf,
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F.; Busseron, E.; Montero, J.-L. Org. Lett. 2008, 10, 753–756; (j) Liu, Y.; Bruneau, A.;
He, J.; Abliz, Z. Org. Lett. 2008, 10, 765–768.
(400 MHz, acetone-d6, room temperature)
d (ppm): 9.56 (d,
J¼6.4 Hz, 4H), 8.87 (d, J¼6.4 Hz, 4H), 7.55 (s, 4H), 7.24 (s, 2H), 5.39 (t,
J¼4.8 Hz, 4H), 4.94 (t, J¼4.8 Hz, 4H), 2.27 (s, 12H). LRESIMS: m/z
655.0 [MꢁPF6]þ (15%), 509.1 [MꢁPF6ꢁHPF6]þ (37%). HRESIMS: m/z
calcd for [MꢁPF6]þ C32H34F6N2O4P, 655.2160, found 655.2162, error
0.3 ppm.
4.7. X-ray crystal data of 1$2$1
3. (a) Brunsveld, L.; Folmer, B. J. B.; Meijer, E. W.; Sijbesma, R. P. Chem. Rev. 2001,
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F. R.; Nagvekar, D. S.; Gibson, H. W. Org. Lett. 1999, 1, 1001–1004; (b) Huang, F.;
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2003, 125, 9367–9371; (d) Huang, F.; Switek, K. A.; Zakharov, L. N.; Fronczek, F.
R.; Slebodnick, C.; Lam, M.; Golen, J. A.; Bryant, W. S.; Mason, P. E.; Rheingold,
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2013–2017.
Crystallographic data: block, orange, 0.20ꢀ0.12ꢀ0.10 mm3,
C82H100F12N6O27P2, FW 1891.62, triclinic, space group P1,
a¼10.697(2), b¼12.361(3), c¼17.412(4) Å,
a
¼77.694(6)ꢃ,
b
¼
77.988(7)ꢃ,
g
¼88.464(9)ꢃ, V¼2199.8(8) Å3, Z¼1, Dc¼1.428 g cmꢁ3
,
T¼113(2) K,
m
¼0.156 mmꢁ1, 24,374 measured reflections, 8629 in-
dependent reflections, 649 parameters, 81 restraints, F(000)¼988,
R1¼0.0696, wR2¼0.1798 (all data), R1¼0.0593, wR2¼0.1690
[I>2s
(I)], max. residual density 0.869 e Åꢁ3, and goodness-of-fit
(F2)¼1.061. Crystallographic data (excluding structure factors) for
the structures in this paper have been deposited with the Cam-
bridge Crystallographic Data Center as supplementary publication
numbers CCDC 697656 and 697657. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: 144 (0)1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk].
4.8. X-ray crystal data of 1$3
Crystallographic data: block, yellow, 0.30ꢀ0.15ꢀ0.09 mm3,
C53H62F12N6O15P2, FW 1313.03, monoclinic, space group P 21/c,
a¼11.8411(13), b¼19.093(2), c¼25.949(3) Å,
a
¼90ꢃ,
b
¼93.804(7)ꢃ,
g
¼90ꢃ, V¼5853.8(11) Å3, Z¼4, Dc¼1.490 g cmꢁ3
,
T¼90 K,
m¼
1.649 mmꢁ1, 29,528 measured reflections, 10,247 independent re-
flections, 802 parameters, 0 restraints, F(000)¼2720, R1¼0.0707,
wR2¼0.1130 (all data), R1¼0.0536, wR2¼0.1070 [I>2
s(I)], max.
residual density 0.66 e Åꢁ3, and goodness-of-fit (F2)¼0.9749.
8. Li, S.; Liu, M.; Zhang, J.; Zheng, B.; Zhang, C.; Wen, X.; Li, N.; Huang, F. Org.
Biomol. Chem. 2008, 6, 2103–2107.
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3724–3728; (b) Orita, A.; Uehara, G.; Miwa, K.; Otera, J. Chem. Commun. 2006,
4729–4731; (c) Orita, A.; Okano, J.; Uehara, G.; Jiang, L.; Otera, J. Bull. Chem. Soc.
Jpn. 2007, 80, 1617–1623.
Acknowledgements
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Viout, P.; Lehn, J. M. Macrocyclic Chemistry; VCH: New York, NY, 1993.
12. Job, P. Ann. Chim. 1928, 9, 113–203.
This work was supported by the National Natural Science
Foundation of China (20604020 and 20774086).
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D. Dissertation, University of Illinois at Urbana-Champaign, Urbana, IL, 1999; (b)
Ashton, P. R.; Ballardini, R.; Balzani, V.; Belohradsky, M.; Gandolfi, M. T.; Philp,
D.; Prodi, L.; Raymo, F. M.; Reddington, M. V.; Spencer, N.; Stoddart, J. F.;
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Supplementary data
Electrospray ionization mass spectra of the complexes 1$2 and
1$3, NMR spectra and other characterizations of 1, 6–9 and in-
termediate products, and other materials. Supplementary data as-
sociated with this article can be found, in the online version, at
doi:10.1016/j.tet.2008.11.081.