Synthesis of a pillar[5]arene dimer by co-oligomerization and its complexation with n-octyltrimethyl ammonium hexafluorophosphate

Article abstract of DOI:10.1016/j.tetlet.2011.06.065

A pillar[5]arene dimer was successfully prepared by co-oligomerization of 1,4-dimethoxybenzene and 1,6-bis(4-butoxyphenoxy)hexane. It was demonstrated that it forms 1:2 complexes with n-octyltrimethyl ammonium hexafluorophosphate both in chloroform and th

Full text of DOI:10.1016/j.tetlet.2011.06.065

Tetrahedron Letters 52 (2011) 4433–4436
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Synthesis of a pillar[5]arene dimer by co-oligomerization and its
complexation with n-octyltrimethyl ammonium hexafluorophosphate
Binyuan Xia a, Jiuming He b, Zeper Abliz b, Yihua Yu c, Feihe Huang a,
⇑
a Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
b Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical Colleage, Bejing 100050, PR China
c Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai 200062, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A pillar[5]arene dimer was successfully prepared by co-oligomerization of 1,4-dimethoxybenzene and
1,6-bis(4-butoxyphenoxy)hexane. It was demonstrated that it forms 1:2 complexes with n-octyltrimeth-
yl ammonium hexafluorophosphate both in chloroform and the gaseous state. A Scatchard plot indicated
that the complexation between them is statistical with an average association constant of 6.0
( 0.4) Â 102 MÀ1 in chloroform.
Received 13 April 2011
Revised 9 June 2011
Accepted 16 June 2011
Available online 23 June 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Pillararene
Co-oligomerization
Self-assembly
Host–guest system
Supramolecular chemistry
The discovery of novel macrocyclic hosts with fascinating struc-
tures and properties has greatly promoted the development of supra-
molecular chemistry. These macrocycles, such as crown ethers,
cyclodextrins, calixarenes and cucurbiturils, have been investigated
in a variety of areas, including molecular recognition,1 nanotechnol-
ogy,2 fluorescent chemosensors,3 drug delivery systems,4 and
supramolecular polymers5 due to their good host–guest interactions,
controllable assembling properties and other interesting abilities. Pil-
lar[5]arene is a new type of macrocyclic host, which was recently
prepared by Ogoshi et al.6 by the condensation reaction of 1,4-dime-
thoxybenzene and paraformaldehyde, using [BF3ÁO(C2H5)2] as the
catalyst. Later, Cao et al.7 firstly obtained pillar[6]arenes by the con-
densation of 1,4-dialkoxy-2,5-bis(alkoxymethyl)benzene catalyzed
by p-toluenesulfonic acid. Then, Li et al.8 investigated the host–guest
properties of pillar[5]arene with a series of paraquats and bis(pyridi-
nium) derivatives. Recently, our group reported the syntheses of
copillar[5]arenes from co-oligomerization9 of different repeating
units, the first pillar[6]arene crystal structure10 and the formation
In recent years, great efforts have been devoted to the construc-
tion of covalently linked macrocycle dimers, such as cyclodextrin di-
mers12 and calixarene dimers,13 because of their specific
applications in carriers, enzyme mimics and supramolecular poly-
mers. However, up to date, the investigations of pillararenes mainly
focus on pillararene monomers.14 Different from pillararene mono-
mers, every oneof thepillararenedimerspossesses twobindingsites
so that they have great potential applications in the construction of
more sophisticated supramolecular structures, such as [n]rotaxanes
and pillararene dimer based A2B2 supramolecular polymers. In order
to provide a necessary supplement to the pillararene family, here we
designed and successfully synthesized the first pillar[5]arene dimer,
which was composed of two pillar[5]arene units linked by a single
aliphatic chain, and explored its host–guest binding with n-octyl-
trimethyl ammonium hexafluorophosphate (G). Scheme 1 presents
possible complexation geometry between them.
We prepared the pillar[5]arene dimer (PD) by co-oligomeri
zation of 1,4-dimethoxybenzene and 1,6-bis(4-butoxyphenoxy)
hexane. First, 1,6-bis(4-hydroxyphenoxy)hexane (1),15 1-bromobu-
tane and K2CO3 in CH3CN were heated at reflux to obtain 1,6-bis(4-
butoxyphenoxy)hexane (2) in 90% yield. Then, a mixture of 8 equiv
of 1,4-dimethoxybenzene, 1 equiv of 2, 10 equiv of paraformalde-
hyde and 10 equiv of [BF3ÁO(C2H5)2] was stirred in 1,2-dichloroeth-
ane under nitrogen atmosphere at room temperature for 5 h. After
purification by preparative thin layer chromatography, PD was ob-
tained in 8% yield.
of pillararene-based supramolecular polymers driven by C–HÁ Á Á
p
interactions.11 Nowadays, pillararenes have attracted more and more
attention not only because their symmetrical and rigid structures
make them excellent building blocks in the construction of interest-
ing supramolecular structures, but also due to their good binding
abilities and specific binding selectivities for particular organic salts
of interest.
In order to investigate the conformational characteristics of
⇑
Corresponding author.
E-mail address: fhuang@zju.edu.cn (F. Huang).
PD, variable-temperature 1H NMR measurements were done in
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.065

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B. Xia et al. / Tetrahedron Letters 52 (2011) 4433–4436
Scheme 1. The complexation between pillar[5]arene dimer PD and G.
toluene-d8 (Fig. S7). Neither of the two peaks corresponding to H4
and H8 on PD were split even at À40 °C because each pillar[5]arene
monomer possesses eight relatively small methoxy groups, result-
ing in a high conformational freedom of the pillar[5]arene dimer.
Partial 1H NMR spectra of PD, a mixture of PD and G, and G in
chloroform-d at 22 °C are shown in Figure 1. The spectrum of the
mixture (spectrum b of Fig. 1) shows only one set of peaks, indicat-
ing fast-exchange complexation between PD and G on the 1H NMR
time scale at 22 °C. After complexation, phenyl protons H1, methy-
lene protons H4, H5, H6, H8, H9, H10 and methyl protons H3, H7 on
PD shifted downfield. Large chemical shifts were observed for
methyl protons Ha and methylene protons Hb, Hc, Hd, He, and Hf
on G due to the shielding effect of the electron-rich cavities of
PD. Methylene protons Hc, Hd, and He shifted upfield even below
0 ppm. The peaks corresponding to Hg on G exhibited a small up-
field shift, while methyl protons Hi shifted downfield obviously.
From these phenomena, a reasonable conclusion was that the lin-
ear guest G was threaded through the two cyclic host cavities of
PD. Two COSY spectra of a solution of 10.0 mM PD in chloro-
form-d (Fig. S8) and a solution of 16.0 mM PD and 18.0 mM G in
Figure 1. Partial 1H NMR spectra (400 MHz, chloroform-d, 22 °C) of (a) 8.00 mM PD; (b) 8.00 mM PD and 9.00 mM G; (c) 9.00 mM G.

B. Xia et al. / Tetrahedron Letters 52 (2011) 4433–4436
4435
chloroform-d (Fig. S10) were obtained to confirm the peak assign-
ments. The host–guest complexation between PD and G was also
verified by a 2D NOESY study (Fig. S11). A cross-peak was observed
between phenyl protons H1 on PD and methylene protons Hf on G.
NOEs were also found between methyl protons H3 on PD and
methyl protons Ha and methylene protons Hc, Hd, and Hf on G.
These evidences further supported that PD and G can form a
threaded structure in chloroform. A job plot16 based on proton
NMR data demonstrated that the complexation between PD and
G was of 1:2 stoichiometry in chloroform-d at room temperature
(Fig. 2).
Further evidence for the formation of the 1:2 complex between
PD and G was obtained by cold spray ionization mass spectrome-
try. A peak was observed at m/z 992.08 (Fig. 3), corresponding to
Figure 3. CSI-TOF mass spectrum of a mixture of PD and G.
[PDꢀG2 À 2PF6]2+
.
To investigate how the two pillar[5]arene binding sites of PD
influence each other during its complexation with G, proton NMR
characterizations were done on a series of chloroform solutions
for which the initial concentration of PD was kept constant at
1.50 mM while the concentration of G was systematically varied.
On the basis of these data, the extent of complexation, p, of pil-
lar[5]arene units was determined and a Scatchard plot was made
(Fig. 4). The linear nature of this plot demonstrated that the com-
plexation between PD and G was statistical, that is, the two pil-
lar[5]arene binding sites behaved independently. From the
intercept and the slope of the Scatchard plot, the average associa-
tion constant (Kav) was determined to be 6.0 ( 0.4) Â 102 MÀ1 for
PDꢀG2. Since K1/K2 = 4:1 for statistical systems (K1 = [PD ꢀ G]/
{[PD][G]} and K2 = [PD ꢀ G2]/{[PD ꢀ G][G]}), K1 and K2 were calcu-
lated to be 9.6 ( 0.6) Â 102 MÀ1 and 2.4 ( 0.2) Â 102 MÀ1, respec-
tively. The value of Kav is lower than the association constant
(K = 1695 115 MÀ1) for the complexation between 1,4-dimeth-
oxypillar[5]arene (P5) and G (see the Supplementary data). This
is understandable considering that a bigger steric hindrance exists
for the complexation between PD and G.
600
400
Y=638 - 562X
200
R2= 0.997
p
0
0.0
0.2
0.4
0.6
0.8
1.0
p
Figure 4. Scatchard plot for the complexation of host PD with guest
chloroform-d at 22 °C. p = fraction of monopillar[5]arene units bound. Error bars
in p: 0.03 absolute; error bars in p/[G]: 0.06 relative.
G in
In conclusion, we have successfully synthesized a pillar[5]arene
dimer, which is composed of two pillar[5]arene units linked by a sin-
gle aliphatic chain. As a necessary supplement to the pillararene
family, pillar[5]arene dimer showed good host–guest binding prop-
erties with n-octyltrimethyl ammonium hexafluorophosphate.
These investigations open up a way for the studies of pillararene
dimers. Future works will focus on the syntheses of new kinds of pil-
lararene dimers, such as the ones linked by functional groups, and
their applications in the construction of more sophisticated
supramolecular systems such as [n]rotaxanes, the formation of
supramolecular polymers, and even the fabrication of organic nano-
tubes with ion conductance properties.
Acknowledgments
This work was supported by the National Natural Science Foun-
dation of China (20834004 and 91027006), the Fundamental Re-
search Funds for the Central Universities (2010QNA3008), and
Zhejiang Provincial Natural Science Foundation of China
(R4100009).
Supplementary data
1.0
0.8
0.6
0.4
0.2
0.0
Supplementary data (synthetic procedures, characterizations,
and other materials) associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.06.065.
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