Highly stable pseudo[2]rotaxanes co-driven by crown ether-ammonium and donor-acceptor interactions

Article abstract of DOI:10.1016/j.tet.2004.05.066

Bis-p-phenylene-34-crown-10 derivatives 1 and 2, bearing one and two dibenzo[24]crown-8 units, respectively, and 4,4′-dipyridinium derivatives of 3·3PF₆ and of 4·4PF₆, bearing one and two ammonium groups, respectively, have been synt

Full text of DOI:10.1016/j.tet.2004.05.066

Tetrahedron 60 (2004) 6137–6144
Highly stable pseudo[2]rotaxanes co-driven by crown
ether–ammonium and donor–acceptor interactions
*
Dai-Jun Feng, Xiao-Qiang Li, Xiao-Zhong Wang, Xi-Kui Jiang and Zhan-Ting Li
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 22 March 2004; revised 14 May 2004; accepted 14 May 2004
Abstract—Bis-p-phenylene-34-crown-10 derivatives 1 and 2, bearing one and two dibenzo[24]crown-8 units, respectively, and 4,40-
dipyridinium derivatives of 3·3PF6 and of 4·4PF6, bearing one and two ammonium groups, respectively, have been synthesized from readily
1
available starting materials. H NMR and UV–vis studies reveal that in polar acetonitrile 1 binds 3·3PF6 to produce pseudo[2]rotaxane
1·3·3PF6 by making use of one donor–acceptor and one electrostatic interaction, whereas 2 binds 4·4PF6 to form pseudo[2]rotaxane 2·4·4PF6
through one donor–acceptor and two electrostatic interactions. The association constants of the two pseudorotaxanes have been determined
by the UV–vis titration method to be 9.1 (^1.0)£103 M21 and 6.5 (^0.7)£105 M21, respectively. The high stability of the new
pseudo[2]rotaxanes has been ascribed to the cooperative interaction of the two different non-covalent forces.
q 2004 Published by Elsevier Ltd.
1. Introduction
pseudorotaxane. However, this seemingly simple approach
will need to modify the cyclic component, which is usually a
daunting work due to the inherent difficulty in the synthesis
of marcocyclic compounds.8,9 Previously, we have demon-
strated that introducing two different non-covalent inter-
Pseudorotaxanes are non-interlocked counterparts of
rotaxanes, in which a linear molecule interpenetrates the
cavities of one or more macrocyclic molecules to form
inclusion complexes.1 This kind of structurally unique
complexes are not only important precursors or ‘inter-
mediates’ for the formation of a large number of rotaxanes
and catenanes,2 but also have been used as new models for
mimicking photosynthetic centers and photo-tuned molecu-
lar devices.3,4 Recently, several stable pseudorotaxanes
have also been utilized to assemble nano-sized functional
materials.5
actions into
a pseudorotaxane architecture could
significantly increase its stability compared to similar
supramolecular systems driven by single non-covalent
interaction.10 Similar approaches have also been utilized
to assemble a number of other interlocked supra-
molecules.11,12 In this paper, we report that complexation
between dibenzo[24]crown-8 and ammonium and donor–
acceptor interaction between electron r0ich bis-p-phenylene-
34-crown-10 and electron deficient 4,4 -dipyridinium could
interact cooperatively to generate a new series of highly
stable pseudo[2]rotaxanes in polar acetonitrile.13,14
Development of efficient approaches for improving or
regulating the stability of pseudorotaxanes is of great
importance for their future applications in materials science
and further functionalizations. The stability of a pseudo-
rotaxane can be remarkably affected by many factors,
including the structures of its linear and cyclic components,
solvent and temperature. Nevertheless, the non-covalent
force between the components obviously plays the most
important role.6,7 Most pseudorotaxanes reported yet make
use of a single non-covalent interaction, such as hydrogen
bonding, electrostatic interaction, solvophobic interaction,
and metal-ligand coordination, as the driving force to induce
their formation. In principle, increase in the number of the
binding sites should be able to improve the stability of a
2. Results and discussion
Compounds 1 and 2 have been designed as the ring
components, in which one bis-p-phenylene-34-crown-10
unit is connected with one and two dibenzo[24]crown-8
units, respectively, whereas cationic compounds 3·3PF6 and
4·4PF6 have been used as linear components, in which the
electron deficient 4,40-dipyridinium unit is linked with
additional alkyl ammonium chains.15 Instead of using the
smaller dibenzo[18]crown-6 unit which possesses an even
stronger binding ability towards ammonium or alkyl-
ammonium,16 we had chosen to use the dibenzo[24]-
crown-8 unit for complexing alkylammonium, since this
Keywords: Rotaxane; crown ether; Donor–acceptor interaction.
*
Corresponding author. Tel.: þ86-21-64163300; fax: þ86-21-64166128;
e-mail address: ztli@mail.sioc.ac.cn
0040–4020/$ - see front matter q 2004 Published by Elsevier Ltd.
doi:10.1016/j.tet.2004.05.066

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D.-J. Feng et al. / Tetrahedron 60 (2004) 6137–6144
larger crown ether can allow the interpenetration of a
secondary ammonium through its cavity and we logically
viewed this work as a first step towards the development of
new generation of pseudo[n]rotaxanes and [n]rotaxanes
(n$3) (Chart 1).13
Scheme 1.
acetonitrile in the presence of potassium carbonate to
produce crown ether 13 in 56% yield. Finally, hydrolysis of
13 with potassium hydroxide in hot water and ethanol afford
14 in 95% yield.
Chart 1.
For the synthesis of compound 2, bromide 17 was first
prepared from the reaction of phenol 15 and excessive
amount of dibromide 16 in refluxing acetonitrile. Then, 17
was hydrogenated in the presence of Pd–C in ethyl acetate
to give 18 in quantitative yield. Compound 18 was then
selectively converted into phenol 19 in 95% yield. Self-
macrocyclization of 19 in the presence of potassium
carbonate in refluxing acetonitrile produced 20 in 56%
yield. This compound was then treated with excessive
amount of diol 8 with palladium(0) as catalyst to afford diol
21. Finally, 21 was reacted with acid 14 with DCC as a
coupling reagent to give 2 in 45% yield (Scheme 2).
The synthesis of compound 1 is provided in Scheme 1.
Macrocycle 7 was first prepared from the reaction of 5 and 6
according to a method we develop previously.10 The
palladium-catalyzed coupling reaction of 7 with compound
8 in hot pyrrolidine produced compound 9 in 92% yield.
Treatment of 9 with crown ether 14 in dichloromethane with
dicyclohexyl carbodiimide (DCC) as condensing reagent
afforded macrocycle 1 in 70% yield. The synthesis of 14
started from diol 10. Thus, treatment of 10 with tosyl
chloride in dichloromethane first afforded 11 in 70% yield.
The latter was then reacted with compound 12 in refluxing

D.-J. Feng et al. / Tetrahedron 60 (2004) 6137–6144
6139
Figure 1. Partial 1H NMR (400 MHz) of (a) 1 (20 mM), (b) 3·3PF6
(20 mM), (c) 1þ3·3PF6 (1:1, 20 mM), (d) 1þ3·3PF6 (1:1, 3 mM), and
(e) 1þ3·3PF6 (1:1, 0.5 mM) in MeCN-d3 at 25 8C.
Adding 1 equiv. of 1 to the solution of 1 equiv. of 3·3PF6 in
MeCN-d3 caused the signals of 3·3PF6 to shift upfield
substantially, as shown in Figure 1. The signals of the
aromatic protons of the bis-p-phenylene-34-crown-10 unit
of 1 also moved upfield significantly. 2D-NOESY 1H NMR
experiments also revealed intermolecular NOE connections
of moderate strength, which are shown in Chart 2 (vide
infra). In addition, the 1:1 solution of the two compounds in
acetonitrile also displayed a charger-transfer absorbance
band at lmax¼435 nm in the UV–vis spectrum. All these
observations indicate that stacking between the electron
deficient and rich aromatic units occurred as a result of the
intermolecular donor–acceptor interaction.19 The a- and
b-H signals of the pyridine units, which produced two sets
of signals in pure 3·2PF6 as a result of its unsymmetric
structure, were further split into four sets of signals (Fig.
1c). The signals had been assigned based on the 2D-NOESY
1H NMR experiments. Adding triethylamine (5 equiv.) to
the 1:1 solution induced the signals to combine to produce
two sets of signals, while two sets of signals were also
Scheme 2.
The syntheses of ionic molecules 3·3PF6 and 4·4PF6 are
shown in Scheme 3. Thus, treatment of compound 22 with
bromide 23 in hot DMF produced tricationic compound
3·3PF6 after purification and anionic exchange with
NH4PF6. In a similar way, dipyridyl 24 was reacted with
23 in hot DMF to yield compound 4·4PF6 after purification
and anionic exchange. For the sake of comparison,
compounds 3·2PF6 and 4·2PF6 were also prepared based
on reported methods.17,18
1
observed in the H NMR spectrum of the 1:1 mixture of 1
and 3·2PF6 in MeCN-d3. Therefore, the above splitting can
be reasonably attributed to the formation of two isomeric
complexes 1·3·3PF6 (A) and 1·3·3PF6 (B) as a result of the
different orientation of the dibenzo[24]crown-8 relative to
its bis-p-phenylene-34-crown-10 unit (Chart 2), although
Scheme 3.

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D.-J. Feng et al. / Tetrahedron 60 (2004) 6137–6144
solution concentration from 60 to 0.5 mM could lead to one
set of the signals to decrease significantly (Fig. 1c–e),
which implied that one of the isomers was converted to
another one at lowered concentration.
Mixing the same equiv. of 2 and 4·4PF6 in MeCN-d3 also
1
induced the H NMR signals of both compounds to shift
substantially, indicative of the formation of complex
2·4·4PF6. As shown in Figure 2, the pyridine a- and b-H
and the pyridine-linking CH2 signals of 4·4PF6 moved
upfield significantly and split into several sets of signals.
Partial aromatic proton signals of 2 also shifted upfield. This
result is similar to that observed for 1 in the mixture of 1
and 3·3PF6. The peaks had also been referred to with the
2D-NOESY 1H NMR experiments, which also revealed
intermolecular NOE connections (Chart 3, vide infra). The
UV–vis spectrum of the solution also displayed a strong
charge-transfer absorbance band (lmax¼456 nm) due to the
intermolecular complexing interaction (Fig. 3, vide infra).
1
As observed for the mixture of 1 and 3·3PF6, the H NMR
splitting of the pyridine proton signals of 4·4PF6 in the
mixture solution might be generated as a result of the
different orientation of the peripheral dibenzo[24]crown-8
relative to the central bis-p-phenylene-34-crown-10 unit of
2. In principle, there was also another possibility: the two
ammoniums of 4·4PF6 bound the two dibenzo[24]crown-8
units, respectively, while its central dipyridinium unit did
not thread through the cavity of the bis-p-phenylene-34-
crown-10 unit of 2. However, this possibility could be ruled
out due to the following results. First, it was reported that
the binding ability of the dibenzo[24]crown-8 unit towards
alkylammonium is very weak (Kassoc¼ca. 50 M21 in
MeCN-d3).20 Secondly, adding excessive amount of 2 to
the 1:1 mixture solution did not impose notable influence on
the ratio of the split pyridine signals of 4·4PF6. Finally, as
shown in Figure 2, all the split signals of the pyridine unit of
4·4PF6 shifted upfield remarkably (0.15–0.55 ppm), which
is obviously impossible for an uncomplexed and unthreaded
dipyridinium unit. In principle, there are three possible
isomers (trans–trans, trans–cis, and cis–cis) for com-
plexes 2·4·4PF6, depending on the different orientation of
the two dibenzo[24]crown-8 units of 2 relative to its bis-p-
phenylene-34-crown-10 unit. As an example, one of the
three isomeric complexes is shown in Chart 3.
Chart 2.
we are not able to differentiate between them at the present
stage.
Increasing the temperature of the 1:1 solution from 25 to
75 8C did not induce the split signals to coalescence or to
shift upfield or downfield greatly, indicating that the binding
was strong and the exchanging processes between the two
isomers was slow on the NMR time scale even at increased
temperature. Reducing the temperature of the solution to
220 8C either had no important influence on the relative
ratio of the two sets of signals. Interestingly, reducing the
The complicated splitting pattern and the lowered resolution
at lower concentration of the 1H NMR spectra of both
complexes made it impossible to utilize the 1H NMR
titration or dilution method to quantitatively study their
binding stability.21 Therefore, UV–vis titration experiments
were carried out at fixed concentration of 1 or 2 by
observing the change of the charge-transfer absorbance with
the increase in the ionic component for both complexes
in acetonitrile.22 Association constants of 9.1
(^1.0)£103 M21
(DG¼5.40 kcal/mol)
and
6.5
(^0.7)£105 M21 (DG¼7.8 kcal/mol) were obtained by a
linear regression of the titration data according to a 1:1
binding mode.23 As an example, the plot of the charge-
transfer absorbance change of the solution of 2 and 4·4PF6
with the addition of the latter is presented in Figure 3. By
1
utilizing the H NMR dilution method,24 the association
Figure 2. Partial 1H NMR (400 MHz) spectrum of (a) 2 (20 mM),
(b) 4·4PF6 (20 mM), and (c) 2þ4·4PF6 (1:1, 20 mM) in MeCN-d3 at 25 8C.
constants of 1·3·2PF6, 2·4·2PF6, and the complex between

D.-J. Feng et al. / Tetrahedron 60 (2004) 6137–6144
6141
Chart 3. One of three possible 2·4·4PF6 isomers.
4. Experimental
4.1. General methods
Melting points are uncorrected. All reactions were carried
out under an atmosphere of nitrogen. The 1H NMR spectra
were recorded on 400 or 300 MHz spectrometers in the
indicated solvents. Chemical shifts are expressed in parts
per million (d) using residual solvent protons as internal
standards. Chloroform (d 7.26 ppm) was used as an internal
standard for chloroform-d. Elemental analysis was carried
out at the SIOC Analytical Center. Unless otherwise
indicated, all commercially available materials were used
as received. All solvents were dried before use following
standard procedures. Compounds 5,25 6,26 7,10 10,27 15,28
and 1629 were prepared according to reported methods.
Figure 3. The plot of the charge-transfer absorption change of the solution
of 2 (3.3 mM) in acetonitrile with the addition of 4·4PF6 from 0.5 to 60 mM.
4.1.1. 1,4,7,13,20,23,26,29,32-Decaoxa-15-(4-hydroxy-
but-1-ynyl)[13,13]paracyclophane (9). To a stirred solu-
tion of compound 7 (0.10 g, 0.22 mmol), Pd(PPh3)4 (83 mg,
0.07 mmol), and cupric iodide (10 mg) in pyrrolidine
(5.0 mL) was added a solution of 3-butyl-1-ol 8 (0.1 mL)
in pyrrolidine (1.5 mL). The mixture was stirred at 80 C for
12 h and then concentrated in vacuo. The resulting residue
was triturated with dichloromethane (50 mL) and the
organic phase washed with hydrochloric acid (1 N, 5 mL),
water (5 mL), brine (5 mL), and dried over sodium sulfate.
Upon removal of the solvent under reduced pressure, the
crude product was subjected to column chromatography
(EtOAc/MeOH 40:1) to give compound 9 as a colorless oil
13 and þNH3C3H7-n PF26 in MeCN-d3 were also determined
to be ca. 200, 190, and 34 M21 (DG¼3.1, 3.1, and 2.1 kcal/
mol), respectively. Comparing the stabilities of the com-
plexes reveals that pronounced cooperative interaction
exists between the two non-covalent forces to drive the
formation of pseudo[2]rotaxane 1·3·3PF6, 2·4·4PF6.
3. Conclusion
1
(0.13 g, 90%). H NMR (CDCl3, 300 MHz): d¼6.92 (d,
In summary, we have reported the self-assembly and
characterizations of two new pseudo[2]rotaxanes in aceto-
nitrile from two new macrocyclic polyethers based on the
donor–acceptor interaction between the electron rich bis-p-
phenylene-34-crown-10 unit and the electron deficient 4,4-
dipyridinium unit and the electrostatic interaction between
the dibenzo[24]crown-8 unit and alkylammonium. The
pseudo[2]rotaxanes exist as stable conformational isomers
as a result of the different orientation of the dibenzo[24]-
crown-8 unit relative to the bis-p-phenylene-34-crown-10 in
the macrocyclic polyethers. These new supramolecular
architectures display high stability in polar acetonitrile due
to the cooperative effect of the two different non-covalent
forces. Future work will be focused on the construction of
new generation of [n]rotaxanes (n.2) with covalently
connected ring components.
J¼3.0 Hz, 1H), 6.81–6.75 (m, 5H), 6.70 (d, J¼9.0 Hz, 1H),
4.08–3.65 (m, 34H), 2.69 (t, J¼5.4 Hz, 2H). HRMS MS
(EI): m/z 605.2956. Calcd for C32H44O11: 605.2960.
4.1.2. Compound 1. A suspension of compounds 7 (0.30 g,
0.50 mmol) and 13 (0.25 g, 0.50 mmol) in dichloromethane
(5 mL) was stirred for 30 min in an ice-bath. A solution of
DCC (0.12 g, 0.60 mmol) and DMAP (0.01 g) in dichloro-
methane (2 mL) was added. The mixture was stirred for 1 h
at room temperature and dichloromethane (20 mL) was
added. The organic phase was washed with hydrochloric
acid (2 M, 20 mL), saturated NaHCO3 solution (20 mL),
water (20 mL£2), brine (20 mL), and dried over sodium
sulfate. Upon removal of the solvent in vacuo, the resulting
residue was purified by column chromatography (AcOEt/

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D.-J. Feng et al. / Tetrahedron 60 (2004) 6137–6144
MeOH 15:1) to afford compound 1 as a colorless oil (0.38 g,
1
5H), 4.21–4.15 (m, 8H), 3.95–3.85 (m, 16H). MS (EI): m/z
492 [M]þ.
70%). H NMR (acetone-d6, 300 MHz): d¼7.68 (d, d, J1¼
2.4 Hz, J2¼9.0 Hz, 1H), 7.56 (d, J¼1.5 Hz, 1H), 7.33 (d,
J¼9.0 Hz, 1H), 6.97–6.94 (m, 2H), 6.91–6.86 (m, 3H),
6.83–6.81 (m, 2H), 6.77–6.75 (m, 4H), 4.46 (t, J¼7.0 Hz,
4H), 4.24–4.18 (m, 2H), 4.12–4.05 (m, 6H), 3.96–3.91 (m,
8H), 3.84–3.81 (m, 8H), 3.77–3.76 (m, 16H), 3.70–3.63
(m, 16H), 2.93 (t, J¼7.0 Hz, 2H). MS (ESI): m/z 1079
[MþH]þ. Anal. Calcd for C57H74O20: C, 63.44; H, 6.91.
Found: C, 63.07; H, 7.02.
4.1.6. 4-[2-[2-[2-(2-Bromo-ethoxy)-ethoxy]-ethoxy]-
ethoxy]-phenyl benzyl ether (17). A mixture of 15
(5.70 g, 28.0 mmol), 16 (45.0 g, 0.14 mol), and potassium
carbonate (7.00 g, 70.0 mmol) in dry acetone (200 mL) was
stirred at room temperature for 1 h and then under reflux for
another 36 h. Upon cooling to room temperature, the solid
was filtered and washed with chloroform. The filtrate was
concentrated under reduced pressure and the resulting
residue was taken up by ether (300 mL). The organic
phase was then washed with dilute sodium carbonate
solution (2 N), water, brine, and dried over sodium sulfate.
After the solvent was removed in vacuo, the crude product
was purified by column chromatography (petroleum ether/
AcOEt 6:1) to afford the desired product as a white solid
4.1.3. 1,2-Bis[2-[2-[2-(2-tosyloxyethoxy)-ethoxy]-
ethoxy]-benzene (11).30 To a stirred solution of compound
10 (9.00 g, 24.0 mmol), tosyl chloride (11.5 g, 60.0 mmol),
and Et3NBnþ Cl2 (0.45 g, 1.90 mmol) in dichloromethane
(200 mL) was added aqueous sodium hydroxide solution
(30%, 36 mL). The mixture was then stirred vigorously at
room temperature for 3 h. The organic phase was separated,
and washed with dilute sodium carbonate, water, brine, and
dried over sodium sulfate. After the solvent was removed
under reduced pressure, the crude product was purified by
column chromatography (CH2Cl2/MeOH 200:1) to obtain
1
(5.00 g, 40%). H NMR (CDCl3): d¼7.45–7.32 (m, 5H),
6.92–6.83 (m, 4H), 5.01 (s, 2H), 4.10–4.07 (m, 2H), 3.85–
3.68 (m, 12H), 3.47 (t, J¼6.0 Hz, 2H). MS (EI): m/z 438
[M]þ. Anal. Calcd for C21H27BrO5: C, 57.41; H, 6.19.
Found: C, 57.64; H, 6.15.
1
compound 11 as an oily solid (13.50 g, 82%). H NMR
(CDCl3, 300 MHz): d 7.90 (d, J¼8.4 Hz, 4H), 7.33 (d,
J¼8.4 Hz, 4H), 6.91(m, 4H), 4.16–4.12 (m, 8H), 3.84–3.80
(m, 4H), 3.70–3.66 (m, 8H), 3.61–3.59 (m, 4H), 2.43 (s,
6H). MS (EI): m/z 683 [MþH]þ.
4.1.7. 4-[2-[2-(2-Propoxy-ethoxy)-ethoxy]-ethoxy]phenol
(18). A suspension of compound 17 (23.0 g, 44.0 mmol) and
Pd–C (10%, 2.00 g) in ethyl acetate (400 mL) was stirred at
room temperature under 1 atom of hydrogen gas for 8 h.
The solid was then removed by filtration through celite. The
filtrate was evaporated under reduced pressure and the
resulting residue purified by column chromatography
(CH2Cl2/AcOEt 30:1) to afford compound 18 as a colorless
4.1.4. Ethyl 6,7,9,10,12,13,20,21,23,24,6,27-dodeca-
hydrodibenzo[b,n][1,4,7,10,13,16,19,22]octaoxacyclo-
tetracosine-2-carboxylate (13). A suspension of 11
(6.14 g, 9.00 mmol) and potassium carbonate (5.04 g,
36.0 mmol) in acetonitrile (450 mL) was stirred at room
temperature for 20 min. Then, a solution of 12 (1.62 g,
9.00 mmol) in acetonitrile (50 mL) was added. The mixture
was heated under reflux for 48 h and the solid then
concentrated under reduced pressure. The resulting residue
was triturated with dichloromethane (200 mL). The organic
phase was washed with dilute hydrochloric acid, water,
brine, and dried over sodium sulfate. Upon removal of the
solvent, the oily residue was purified with column
chromatography (CH2Cl2/MeOH 99:1) to produce gave
compound 13 as an oily solid (2.62 g, 56%). 1H NMR
(CDCl3, 300 MHz): d¼7.65 (d, d, J1¼1.8 Hz, J2¼8.7 Hz,
1H), 7.54 (d, J¼1.8 Hz, 1H), 6.83–6.89 (m, 5H), 4.34 (q,
J¼7.2 Hz, 2H), 4.13–4.24 (m, 8H), 3.90–3.98 (m, 8H),
3.79–3.86 (m, 8H), 1.38 (t, J¼6.9 Hz, 3H). MS (EI): m/z
520 [M]þ. Anal. Calcd for C27H36O10: C, 62.36; H, 6.98.
Found: C, 62.05; H, 6.78.
1
oil (15.0 g, 98%). H NMR (CDCl3, 300 Hz): d¼6.74 (d,
J¼1.2 Hz, 4H), 5.58 (s, 1H), 4.03–4.00 (m, 2H), 3.83–3.77
(m, 4H), 3.75–3.67 (m, 8H), 3.44 (t, J¼6.0 Hz, 2H). MS
(EI): m/z 348 [M]þ. Anal. Calcd for C14H21BrO5: C, 48.15;
H, 6.06. Found: C, 48.02; H, 5.92.
4.1.8. 2-Bromo-4-[2-[2-[2-(2-bromo-ethoxy)-ethoxy]-
ethoxy]-ethoxy]phenol (19). To a solution of compound
18 (10.8 g, 31.0 mmol) in dichloromethane (100 mL),
cooled in an ice bath, was added dropwise a solution of
bromine (1.7 mL, 31.0 mmol) in dichloromethane (50 mL)
within 30 min. The mixture was stirred at 0 8C for 1 h. Then,
aqueous NaHSO3 solution (5%, 100 mL) was added.
Stirring was continued until the mixture became colorless.
The organic phase was washed with water (50 mL£2), brine
(50 mL), and dried over sodium sulfate. Upon removal of
the solvent in vacuo, the crude produce was purified by flash
chromatography (AcOEt/petroleum ether 1:4) to produce
1
compound 19 as a colorless oil (12.5 g, 95%). H NMR
4.1.5. 2,5,8,11,18,21,24,27-Octaoxa-tricyclo[26.4.0.012,17]-
dotriaconta-1(28),12,14,16,29,31-hexaene-14-carboxylic
acid (14). To a solution of 13 (1.00 g, 2.00 mmol) in ethanol
(15 mL) was added aqueous potassium hydroxide solution
(4 N, 3 mL). The solution was then heated under reflux
for 12 h. Upon cooling to room temperature, hydrochloric
acid was added to pH¼4. The solution was concentrated
in vacuo and the resulting residue was washed with water
thoroughly and dried. The resulting white solid was
recrystallyzed from ethanol to give compound 14 (0.85 g,
(CDCl3): d¼7.03 (d, J¼3.0 Hz, 1H), 6.92 (d, J¼9.0 Hz,
1H), 6.92 (d, d, J1¼3.0 Hz, J2¼9.0 Hz, 1H), 5.44 (s, 1H),
4.06–4.03 (m, 2H), 3.84–3.78 (m, 4H), 3.74–3.68 (m, 8H),
3.46 (t, J¼6.0 Hz, 2H). HRMS (EI) Calcd for C14H20Br2O5:
425.9676. Found: 448.9576 [MþNa]þ.
4.1.9. 1,4,7,13,20,23,26,29,32-Decaoxa-15,34-dibromo-
[13,13]paracyclophane (20). A suspension of phenol 19
(0.85 g, 2.00 mmol) and potassium carbonate (1.40 g,
10.0 mmol) in acetonitrile (80 mL) was heated under reflux
for 24 h and then cooled to room temperature. The solid was
filtered off and the filtrate was concentrated under reduced
pressure. The resulting residue was triturated in 100 mL of
1
95%) as a white solid. Mp 184–1868 [182–183 8C31]. H
NMR (CDCl3, 300 MHz): d¼7.72 (d, d, J1¼1.5 Hz,
J2¼8.4 Hz, 1H), 7.56 (d, J¼2.1 Hz, 1H), 6.89–6.86 (m,

D.-J. Feng et al. / Tetrahedron 60 (2004) 6137–6144
6143
dichloromethane and the organic phase was washed with
dilute sodium carbonate solution, water, brine, and dried
over sodium sulfate. Upon removal of the solvent in vacuo,
the crude produce was purified by column chromatography
(CH2Cl2/AcOEt 2:1) to afford compound 20 as a white solid
(0.38 g, 56%). Mp 104–106 8C. 1H NMR (CDCl3): d¼7.08
(d, J¼3.0 Hz, 2H), 6.78 (d, J¼9.0 Hz, 2H), 6.73 (d, d,
J1¼9.0 Hz, J2¼3.0 Hz, 2H), 4.04–4.07 (m, 4H), 3.99–3.96
(m, 4H), 3.88–3.85 (m, 4H), 3.83–3.80 (m, 4H), 3.78–3.75
(m, 4H), 3.70–3.64 (m, 12H). MS (EI): m/z 694 [M]þ. Anal.
Calcd for C28H38Br2O10: C, 48.43; H, 5.52. Found: C,
48.44; H, 5.51.
J¼6.6 Hz), 5.19 (t, J¼7.5 Hz, 2H), 4.74 (s, 3H), 3.62
(t, J¼6.9 Hz, 2H,), 2.86 (m, 2H). MS (ESI): m/z 542
[M22PF26 ]2þ. Anal. Calcd for C14H20F18N3P4: C, 22.48; H,
3.14; N, 6.55. Found: C, 22.39; H, 3.14; N, 6.24.
4.1.14. Compound 4·4PF6. The compound was prepared as
a yellowish solid (60%) from the reaction of 22 and 23
(2.2 equiv.) according to the method described for 3·3PF6.
1
Mp .255 8C (decom.). H NMR (acetone-d6, 300 MHz):
d¼9.36 (d, J¼7.0 Hz, 4H), 8.87 (d, J¼7.0 Hz, 4H), 5.15–
5.10 (t, J¼7.5 Hz, 4H), 3.53–3.54 (m, 4H), 2.80–2.75 (m,
4H). MS (ESI): m/z 417 [M23PF26 ]3þ. Calcd for
C16H26F24N4P4: C, 22.50; H, 3.07; N, 6.56. Found: C,
22.64; H, 3.20; N, 6.51.
4.1.10. 1,4,7,13,20,23,26,29,32-Decaoxa-15,34-di(4-
hydroxy-but-1-ynyl)[13,13]paracyclophane (21). This
compound was prepared as a white solid (81%) from the
reaction of 8 and 19 according to the method described for
9. Mp 72–74 8C. 1H NMR (CDCl3): d¼6.87 (d, J¼3.0 Hz,
2H), 6.66 (d, J¼9.0 Hz, 2H), 6.75 (d, d, J1¼9.0 Hz,
J2¼3.0 Hz, 2H), 4.05–4.02 (m, 4H), 3.96–3.94 (m, 4H),
3.88–3.85 (m, 4H), 3.82–3.70 (m, 12H), 3.69–3.68 (m,
12H), 3.01 (br, 2H), 2.66 (t, J¼6.0 Hz, 4H). MS (EI): m/z
672 [M]þ. Anal. Calcd for C36H48O12: C, 64.28; H, 7.19.
Found: C, 63.96; H, 6.80.
4.2. Binding studies
For UV–vis absorption titration experiments, 2.5 mL of the
mixture solution in acetonitrile with the fixed [1] or [2] and
the changing concentration of the ionic components was
placed in a cuvette and the UV–vis absorption spectra were
sequentially recorded (15–20 samples). The values of the
absorbance at the fixed wavelength were used. Origin 6.0
software was used to fit the data to a 1:1 binding isotherm:
DA¼(DAmax/[H])£{0.5[G]þ0.5([H]þKd)20.5[[G]2þ(2[
G](Kd-[H])þ(Kdþ[H])2)1/2]}, where [G] is the concen-
tration of the changing component (3·3PF6 or 4·4PF6), [H]
is the fixed concentration of the macrocycle (1 or 2), and
4.1.11. Cyclophane 2. This compound was prepared as a
white solid (45%) from the reaction of 14 (2 equiv.) and 21
according to the method described for 1. Mp 92–94 8C. 1H
NMR (acetone-d6, 300 MHz): d¼7.67 (d, d, J1¼2.4 Hz,
J2¼9.0 Hz, 2H), 7.57 (d, J¼2.4 Hz, 2H), 6.91–6.82 (m,
12H), 6.72 (d, J¼2.4 Hz, 4H), 4.45 (t, J¼7.2 Hz, 4H), 4.19–
4.14 (m, 16H), 4.04 (m, 4H), 3.96–3.91 (m, 20H), 3.85–
3.79 (m, 24H), 3.74–3.66 (m, 16H), 2.88 (t, J¼7.5 Hz, 4H).
HRMS (MALDI-tof): Calcd for C86H108O30: 1621.6192.
Found: 1643.6818, [MþNa]þ.
Kd¼(Kassoc
)
21. For the 1H NMR dilution study, the
following equation was used to fit the 1:1 binding isotherm:
Dd¼d2d0¼Ddmax{1þ(0.5/Kassoc[H])2[(0.5/Kassoc[H])2þ
1/Kassoc[H]]1/2}, where d¼chemical shift of the probe signal
in monomer/complex mixture, d0¼chemical shift of the
probe signal in monomer.24 Association constants reported
are the average values of two experiments.
4.1.12. 1-Met0hyl-[4,40]bipyridylium iodide (22·I). A
solution of 4,4 -dipyridyl (1.80 g, 11.0 mmol) and methyl
iodide (0.80 mL, 14.0 mmol) in dichloromethane was
stirred at reflux for 2 h. After the mixture was cooled to
room temperature, the solid was filtered and washed with
ethyl acetate thoroughly, the crude product was recrystal-
lyzed from methanol to give the desired compound as a
yellow solid (2.86g, 95%). Mp .248 8C (244 8C, lit.32). 1H
NMR (DMSO-d6, 300 MHz): d¼9.14 (d, J¼6.6 Hz, 2H),
8.87 (d, J¼6.0 Hz, 2H), 8.62 (d, J¼6.6 Hz, 2H), 8.04 (d,
J¼6.0 Hz, 2H), 4.38 (s, 3H). MS (ESI): m/z 171 [M2I]þ.
Acknowledgements
We thank the Ministry of Science and Technology (No.
G2000078101), the National Natural Science Foundation,
and the State Laboratory of Bio-Organic and Natural
Products Chemistry of China for support of this work.
References and notes
4.1.13. 3-(10-Methyl-4,40-bipyridinium)propylammo-
nium tris(hexafluorophosphate) (3·3PF6). A suspension
of the compound 22·I (1.30 g, 4.80 mmol) and 3-bromo-
propylamine hydro bromide 23 (1.30 g, 5.50 mmol) in DMF
(25 mL) was stirred at 60 8C for 24 h. After the mixture was
cooled to room temperature, the solid was filtered, washed
with methanol and ether thoroughly, and then dissolved in
water (ca. 5 mL). Then, a saturated aqueous ammonium
hexfluorophosphate was added dropwise to the above
solution until no precipitate was generated. The precipitate
was filtered and washed with cold water. After recrystalli-
zation from methanol, the desired product was obtained as a
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