Efficient syntheses of novel cryptands based on bis(m-phenylene)-26-crown-8 and their complexation with paraquat

Article abstract of DOI:10.1002/ejoc.200901294

High-yielding syntheses of two novel cryptands based on bis(m-phenylene)-26-crown-8 are reported. One-step [2+2] cyclization of methyl 3,5-dihydroxybenzoate with tri(ethylene glycol) ditosylate under pseudo-high-dilution conditions gave BMP26C8 (1) in 28% yield. Reduction of 1 with LAH, followed by deprotonation (NaH) and alkylation with propargyl bromide, afforded the dialkynated BMP26C8 (3) in high yield (two-step 84%). Unimolecular macrocyclization of 3 through copper(II) -mediated Eglinton coupling generated the diacetylene-containing cryptand 4 in 97 % yield. Pd/Ccatalyzed hydrogenation of 4 yielded the cryptand 5 (93 %). Their structures were confirmed by NMR, ESI-MS, and Xray analysis. The complexation behavior of these new cryptands with paraquat was also studied, and it was found that these cryptands bind paraquat more strongly than the corresponding BMP26C8. The association constants (K ₁ and K₂) in acetone solution were determined to be K ₁ = 914 M^-1, K₂ = 229 M^-1 for complex 4₂-6 and K₁ = 758 M^-1, K₂ = 190 M^-1 for complex 5₂,6. Moreover, the two new [3]pseudorotaxane-like complexes 4₂,6 and 5₂,6 were also obtained in the solid state, as confirmed by X-ray analysis.

Full text of DOI:10.1002/ejoc.200901294

FULL PAPER
DOI: 10.1002/ejoc.200901294
Efficient Syntheses of Novel Cryptands Based on Bis(m-phenylene)-26-crown-8
and Their Complexation with Paraquat
[
a]
[a]
[a]
[a]
[a]
Zhikai Xu, Xinmin Huang, Jidong Liang, Suhui Zhang, Songgen Zhou,
[a]
[a]
[a]
Mujuan Chen, Mingfei Tang, and Lasheng Jiang*
Keywords: Cryptands / Macrocycles / Host–guest systems
High-yielding syntheses of two novel cryptands based on
bis(m-phenylene)-26-crown-8 are reported. One-step [2+2]
cyclization of methyl 3,5-dihydroxybenzoate with tri(ethy-
lene glycol) ditosylate under pseudo-high-dilution conditions
gave BMP26C8 (1) in 28% yield. Reduction of 1 with LAH,
followed by deprotonation (NaH) and alkylation with propar-
gyl bromide, afforded the dialkynated BMP26C8 (3) in high
yield (two-step 84%). Unimolecular macrocyclization of 3
through copper(II)-mediated Eglinton coupling generated
the diacetylene-containing cryptand 4 in 97% yield. Pd/C-
catalyzed hydrogenation of 4 yielded the cryptand 5 (93%).
Their structures were confirmed by NMR, ESI-MS, and X-
ray analysis. The complexation behavior of these new crypt-
ands with paraquat was also studied, and it was found that
these cryptands bind paraquat more strongly than the corre-
sponding BMP26C8. The association constants (K
acetone solution were determined to be K = 914
–1, K
= 190
·6. Moreover, the two new [3]pseudorotaxane-like
complexes 4 ·6 and 5 ·6 were also obtained in the solid state,
1
and K
2
) in
–
1
1
M
, K =
2
–
1
–1
229
M
for complex 4
2
·6 and K
1
= 758
M
2
M
for
complex 5
2
2
2
as confirmed by X-ray analysis.
cryptands.[7,8] However, the preparation of these crown-
Introduction
ether-based cryptands was mostly in yields of only 21–
Mechanically interlocked structures such as rotaxanes
and catenanes have attracted much attention not only be-
cause of the fascinating aspect of their topologies but also
thanks to their applicability in the preparation of nanoscale
[7a–7h]
50%.
One possible reason for this is the difficulties
inherent in the cyclization of a difunctionalized bisphen-
[7b,7i,8b]
ylene crown ether with another small molecule.
Con-
sequently, it is still important to improve the synthetic effi-
ciency and to design novel cryptands capable of binding
different organic guests, which could provide many oppor-
tunities for the development of new specific supramolecular
systems. Here we report a high-yielding synthesis of the
[
1]
[2]
molecular electronic devices. Crown ethers, cucurbit[n]-
[
3]
[4]
[5]
urils,
calixarenes,
cyclodextrins,
and other com-
[
6]
pounds have been widely used as hosts in the preparation
of these interlocked structures because they readily allow
formation of host–guest complexes with ionic and neutral
guest molecules. Recently it has been shown that crown-
ether-based cryptands, including those based on bis(m-
phenylene)-32-crown-10 and on bis(m-phenylene)-26-
crown-8, are powerful hosts that complex with paraquat,
paraquat derivatives, diquats, and secondary ammonium
salts much more strongly than the corresponding simple
novel cryptands 4 and 5, both based on bis(m-phenylene)-
[10]
26-crown-8, by copper(II)-mediated Eglinton coupling
and, in the case of 5, subsequent Pd/C-catalyzed reduction
Scheme 1). Furthermore, the complexation behavior of
(
these new cryptands with paraquat 6 was also investigated
and it was found that they can form [3]pseudorotaxane-like
complexes with paraquat both in solution and in the solid
state.
[
7]
crown ethers. The successful formation of host cryptands
has undoubtedly played key roles in the construction of dif-
ferent kinds of complexes with specific structures and prop-
erties. During the past decade, Gibson, Huang, and co- Results and Discussion
workers have made a significant contribution to the synthe-
ses, complexation, and applications of crown-ether-based
The efficient formation of the crown ether 1 was vital for
successful syntheses of these novel cryptands, as depicted in
Scheme 1. This compound had previously been prepared by
Gibson’s group by a one-step method from methyl 3,5-dihy-
droxybenzoate and tri(ethylene glycol) dichloride in the pres-
[
a] School of Chemistry and Environment, South China Normal
University,
Guangzhou, 510631, P. R. of China
Fax: +86-20-39310187
[9d]
ence of NaH in DMF. The yield, however, was reported to
E-mail: jianglsh@scnu.edu.cn
be only 6%. In this study we modified the one-step strategy,
resulting in a remarkable improvement in the yield. Use of
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901294.
1904
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1904–1911

Novel Cryptands Based on Bis(m-phenylene)-26-crown-8
Scheme 1. Syntheses of two cryptands based on bis(m-phenylene)-26-crown-8.
tri(ethylene glycol) ditosylate in place of the dichloride in a
reaction with methyl 3,5-dihydroxybenzoate in acetonitrile at
reflux and in the presence of K CO under pseudo-high-di-
2
3
lution conditions generated the desired crown ether 1 in 28%
yield, which is much higher than reported.[
7m,9d]
This modi-
fied procedure is practical, easily performed, and high-yield-
ing. The improvement may be accounted for by a number of
factors. Firstly, the more soluble potassium tosylate gener-
ated in this reaction could have templated the cyclization
process. Secondly, the less polar acetonitrile is favorable for
cyclization. Thirdly, pseudo-high-dilution conditions can
prevent polymer or oligomer formation. After reduction with
LAH, followed by deprotonation and alkylation with pro-
pargyl bromide, the dialkyne compound 3 (Figure 1, a) was
obtained in high yield (Scheme 1).
The final step of the synthesis of a crown-ether-based
cryptand usually includes a second cyclization reaction. Al-
though several reactions, such as esterification,[ have been
reported for this purpose, the cyclization yields are often
less than 50%. Here we employed the copper(II)-mediated
Eglinton coupling for the final cyclization. The cryptand 4
was generated in 97% yield by slow addition of the dialkyne
8]
3
over 2 d (i.e., pseudo-high-dilution conditions) to an ace-
tonitrile/dichloromethane (1:4) solution of Cu(OAc) under
2
O at 45–50 °C. From the cryptand 4, the bis(m-phenylene)-
2
26-crown-8-based cryptand 5 was then synthesized in 93%
yield by Pd/C-catalyzed reduction under H . The yields
2
both for cryptand 4 and for cryptand 5 are much higher
than those of analogues reported in the literature pre-
[
7]
viously. We have therefore developed a new and high-
yielding approach for syntheses of crown-ether-based
cryptands.
Figure 1. Ball-and-stick views of the X-ray structures of: a) com-
pound 3, b) cryptand 4, and c) cryptand 5. All hydrogen atoms
have been omitted for clarity.
Eur. J. Org. Chem. 2010, 1904–1911
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1905

L. Jiang et al.
FULL PAPER
The structures of these new cryptands have been fully tons H on 6 and the benzyl methylene protons H and H Ј
γ
3
3
1
characterized by spectroscopic methods, including
H
on 4 and 5 and the α-CH CH O protons H and H Ј on 4
2 2 5 5
1
3
NMR, C NMR, ESI-MS, HRESI-MS, and MALDI- and 5 were also shifted upfield, whereas the alkyne α-pro-
TOF-MS. Fortunately, single crystals both of cryptand 4 tons H , alkane protons H Ј, β-CH CH O protons H and
4
4
2
2
6
and of cryptand 5 were also obtained.
H Ј, and γ-CH CH O protons H and H Ј on 4 and 5 were
6 2 2 7 7
A single crystal of cryptand 4 suitable for X-ray analysis shifted downfield.
was grown by slow evaporation of methanol solution. As
shown by its crystal structure (Figure 1, b), the catechol
rings are not parallel (angle 48.77°) and the centroid–
centroid distance between the catechol rings is 5.869 Å.
A single crystal of cryptand 5 was also obtained by slow
evaporation of a solution of cryptand 5 in acetone at room
temperature. The X-ray structure (Figure 1, c) shows that
the angle between the planes of the aromatic rings is 73.54°;
the distance between the centroids of the aromatic rings is
5.781 Å. The crystal data and the experimental parameters
are summarized in the Supporting Information. The crystal
structures of cryptands 4 and 5 show that both of them are
slightly collapsed, but the cavities are accessible. Further-
more, the cavity of cryptand 4 is slightly more open than
that of cryptand 5 in the solid state (parts b and c in Fig-
ure 1).
With these new cryptands to hand, we turned our atten-
tion to their application in host–guest chemistry. Complex-
ation between either cryptand 4 or cryptand 5 and paraquat
6
(Scheme 2) was studied. Mole ratio plots[11] (Figure 2)
based on proton NMR spectroscopic data demonstrated
that both of these complexes were of 2:1 stoichiometry in
solution. Equimolar solutions of either cryptand 4 or cryp-
tand 5 and paraquat 6 in [D ]acetone were yellow as a result
of charge transfer between the electron-rich aromatic rings
6
Figure 2. Mole ratio plots for a) cryptand 4 and paraquat 6, and
b) cryptand 5 and paraquat 6 in [D ]acetone. [4] or [5] = 8.00 m.
6
0
0
of the cryptands and the electron-poor aromatic ring of
1
paraquat. The H NMR spectra of 6 with either 4 or 5 (1:1)
in [D ]acetone solution at room temperature show that the
To improve understanding of the complexation behavior
6
chemical shifts of the protons of the complex are signifi- of the cryptands 4 or 5 with paraquat 6, proton NMR char-
cantly different from those of their free components. Only acterization was carried out with a series of acetone solu-
one set of peaks was found in each of the proton NMR tions in which the initial concentration of guest 6 was kept
spectra of solutions of 4 or 5 with 6, indicating that ex- constant at 0.5 m while the initial concentrations of hosts
change in these two complexation systems was fast on the 4 or 5 were systematically varied. From these proton NMR
proton NMR timescale. The chemical shift changes of the spectroscopic data, the extent of complexation (ρ) was de-
[
12]
protons of 4 and 5 showed almost the same characteristics termined by the Benesi–Hildebrand method and Scatch-
[
13]
after complexation with 6. Partial proton NMR spectra of ard plots
were made (Figure 4). The linear natures of
4, 5, 6, a mixture of 4 and 6, and a mixture of 5 and 6 are these plots demonstrated that the two N-methylpyridinium
shown in Figure 3. After complexation, the resonances of binding sites in paraquat 6 are independent of each other
the pyridinium protons H and H on 6 and the aromatic during the complexation between 6 and either 4 or 5. From
α
β
protons H , H , H Ј, and H Ј on 4 and 5 are shifted signifi- the slope of the top plot we determined the association con-
1
2
1
2
–1
cantly upfield, which indicates the existence of π-stacking stants K1 and K2 for 4 and 6 to be 914Ϯ13  and
interactions between the π-donors (aromatic rings) and the 229Ϯ3  , respectively (Figure 4, a). From the slope of
–1
[14]
π-acceptor (bipyridinium). Furthermore, the N-methyl pro- the bottom plot (Figure 4, b), the association constants K
1
758Ϯ7 –1 and K = 190Ϯ2  were estimated for 5 and
–1
=
2
6
42
. The average association constants (K ) for the complexes
av
·6 and 5 ·6 are K = 572Ϯ8 –1 and Kav2 = 474Ϯ5  ,
–1
2 av1
respectively. The value of Kav is higher for the complex 4 ·6
2
than for the complex 5 ·6. Both of these average association
2
constants Kav1 and K
are higher than the K value for
av2
a
BMP26C8·6 (390 –1 in [D ]acetone ), indicating that the
[7f]
6
binding affinities of cryptands 4 and 5 for paraquat are
7]
Scheme 2. Structure of paraquat 6.
906
higher than that of the corresponding crown ether.[
1
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1904–1911

Novel Cryptands Based on Bis(m-phenylene)-26-crown-8
Figure 3. Partial proton NMR spectra (400 MHz, [D
d) 5 (5.00 m) with 6 (5.00 m), and e) cryptand 5.
6
]acetone, 22 °C) of a) cryptand 4, b) 4 (5.00 m) with 6 (5.00 m), c) paraquat 6,
mass spectrum of a mixture of 5 and 6 with molar ration
2
:1, the base peak was at m/z 331.14, corresponding to [6 –
+
PF ] . Four peaks for 5 ·6 were observed at m/z 683.69
6
2
2+
2+
(84%) [5 ·6 – 2 PF ] , 505 [5 ·6 – PF + 4 H] , 473.53
2 6 2 6
3+
(42%) [5 ·6 – 2 PF + 3 H O] , and 388.64 (83%) [5 ·6 –
2
6
2
2
4
+
PF + Na + H O + H] . In addition, one peak was ob-
served for 5·6 at m/z 921.27 (53%) [5·6 – PF ] . However,
6
2
+
6
no peaks corresponding to other stoichiometries were
found in complexation of 6 either with 4 or with 5.
Further evidence from X-ray analysis unambiguously
confirmed the complex formation. X-ray analysis was car-
ried out with a yellow crystal of 4 ·6 grown by slow evapo-
2
ration of an acetone solution of 6 with excess 4, which con-
firmed the 2:1 stoichiometry of the complexation between
4
and 6 in solution (Figure 5). The complex 4 ·6, a [3]pseu-
2
[
7f]
dorotaxane-like structure, is stabilized in the solid state
by hydrogen bonding between host and guest and face-to-
face π-stacking interaction between the aromatic rings of 4
and the pyridinium rings of 6. It has recently been reported
that a different bis(m-phenylene)-26-crown-8-based crypt-
and, with a tri(ethylene glycol) third chain, can also form
a 2:1 complex with 6 in the solid state, as confirmed by
Figure 4. Scatchard plots for the complexation of 6 with a) 4, and
b) 5 in [D ]actone at 22 °C; ρ = fraction of cryptand unit bound.
6
[
7e]
single-crystal analysis. As in that complex, the N-methyl
Electrospray ionization mass spectra of solutions of 4 hydrogen atoms of 6 are not involved in hydrogen bonding
and 6 and of 5 and 6 in acetonitrile confirmed the 2:1 stoi- between the host and the guest, and the two cryptand host
chiometries of these complexes. For the mass spectrum of molecules of the complex are also connected by two hydro-
a solution of 4 and 6 with molar ration 2:1, the base peak gen bonds (F in Figure 5). However, there are some dif-
+
was at m/z 331.12, corresponding to [6 – PF ] . Three peaks ferent characteristics because of the different structures of
6
[
7e]
were found for 4 ·6 at m/z 807.20 (24%) [4 ·6 – 2 CH + 3 the two cryptand hosts. In the previous complex, four α-
2
2
3
2
+
2+
H] , 675.45 (42%) [4 ·6 – 2 PF ] , and 384.56 (69%) pyridinium hydrogen atoms of 6 form six hydrogen bonds
4 ·6 – PF + Na + H O + H] . Moreover, one peak was directly with -CH CH O oxygen atoms of the cryptand
found for 4·6 at m/z 913.21 (37%) [4·6 – PF ] . For the host. Here, in the crystal structure of 4 ·6, two α-pyridinium
2
6
4
+
[
2 6 2 2 2
+
6
2
Eur. J. Org. Chem. 2010, 1904–1911
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1907

L. Jiang et al.
FULL PAPER
Figure 5. Ball-and-stick views of the X-ray structure of complex 4
2
·6. The PF
6
counterions, solvent molecules, and hydrogen atoms have
been omitted for clarity, except for those on 6 or involved in hydrogen bonding. Hydrogen bond parameters: H···O distances [Å], C–
H···O angles (degrees), C···O distances [Å] for A) 2.70, 153.42, 3.53; B) 2.71, 142.75, 3.50; C) 2.37, 143.86, 3.17; D) 2.48, 145.25, 3.29;
E) 2.53, 147.68, 3.35; F) 2.58, 160.34, 3.51. Face-to-face π-stacking parameters: centroid–centroid distances [Å] 3.79, 3.77; ring plane/ring
plane inclinations (degrees): 7.72, 8.75.
hydrogen atoms of 6 are directly connected to the host tween the host and the guest, and two α-pyridinium hydro-
through four hydrogen bonds (A and B in Figure 5), and gen atoms of 6 are directly hydrogen-bonded to ethylenoxy
four β-pyridinium hydrogen atoms of 6 are directly hydro- oxygen atoms of 5 through four hydrogen bonds (A and B
gen-bonded to ethylenoxy oxygen atoms of 4, forming six in Figure 4). In addition, no hydrogen-bonding water brid-
hydrogen bonds (C, D, and E in Figure 5), unlike in the ges between cryptand host and paraquat guest are observed
case of the analogous complex connected by four hydrogen in the crystal structure of 5 ·6 either (Figure 6). Interest-
2
bonds with β-pyridinium hydrogen atoms of 6.[ Unlike in ingly, four β-pyridinium hydrogen atoms of 6 are directly
7e]
analogous cryptands reported in the literature,[
7c,7e–7h,7l]
connected to the host through eight hydrogen bonds, unlike
[
7c,7e–7h,7l]
there are no water molecules serving as hydrogen bonding in the complex 4 ·6 and analogous cryptands.
Also
2
bridges in the crystal structure of 4 ·6 (Figure 5).
as in complex 4 ·6 (Figure 5), the distances between each
2
2
The 2:1 stoichiometry of complexation between 5 and 6 pyridinium ring of 6 and the phenylene rings of 5 are mostly
in solution was also confirmed by its solid-state structure equal, presumably in order to maximize face-to-face π-
Figure 6). X-ray quality,[ yellow, single crystals of 5 ·6 stacking interaction between the electron-rich cryptand
15]
(
2
were grown by slow evaporation of an acetone solution of host and the electron-poor pyridinium paraquat guest (Fig-
with excess 5. As in the 2:1 complex between cryptand 4 ure 6). The centroid–centroid distance between the phenyl-
and paraquat 6, the complex 5 ·6, a [3]pseudorotaxane-like ene rings of the cryptand host in 4 ·6 is 6.91 Å, whereas in
6
2
2
structure, is stabilized by hydrogen bonding and face-to- 52·6 this distance is 6.93 Å, indicating slightly weaker
face π-stacking interaction between host and guest in the charge-transfer interactions between cryptand hosts and
solid state. Also as in complex 4 ·6, none of the N-methyl pyridinium binding sites in 5 ·6. This result is consistent
2
2
hydrogen atoms of 6 is involved in hydrogen bonding be- with the weaker average association constant for the com-
Figure 6. Ball-and-stick representations of the X-ray structure of complex 5
atoms have been omitted for clarity, except for those on 6 or involved in hydrogen bonding. Hydrogen-bond parameters: H···O distances
Å], C–H···O angles (degrees), C···O distances [Å] for A) 2.45, 149.41, 3.29; B) 2.47, 145.09, 3.28; C) 2.48, 151.57, 3.33; D) 2.63, 141.70,
.41; E) 2.68, 151.17, 3.52; F) 2.68, 145.54, 3.49; Face-to-face π-stacking parameters: centroid–centroid distances [Å] 3.96, 3.83; ring plane/
ring plane inclinations (degrees): 7.74, 8.30.
2 6
·6. The PF counterions, solvent molecules, and hydrogen
[
3
1908
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1904–1911

Novel Cryptands Based on Bis(m-phenylene)-26-crown-8
plexation between cryptand 5 and paraquat 6 than for cryp- 166.68, 15969, 131.72, 107.83, 107.00, 70.90, 69.46, 67.63,
+
52.13 ppm. MS (ESI): m/z (%) = 582.31 [M + NH
4
] .
tand 4 and paraquat 6.
Synthesis of Compound 2: LiAlH
der N at 0 °C to a suspension of compound 1 (1.13 g, 2 mmol) in
dry THF (50 mL). The mixture was further stirred for 12 h at room
temperature. The excess LiAlH was quenched with ethyl acetate
4
(0.31 g, 8 mmol) was added un-
2
Conclusions
4
We have synthesized two novel crown-ether-based crypt- and the resulting mixture was neutralized with HCl (2 ). The sys-
ands in high yield, by use of a modified one-step [2+2] tem was extracted with ethyl acetate and CHCl , and the organic
, and concentrated to
give compound 2 (0.99 g, 98%) as a white solid; m.p. 139.0–
3
fractions were combined, dried with MgSO
4
cyclization (to crown ether) and a alkyne coupling reaction
for the key steps. It is believed that this methodology might
find more extensive applications in the preparation of new
macrocycles. It has also been demonstrated by means of
NMR techniques, ESI-MS, and X-ray analysis that these
new cryptands can bind paraquat more strongly than the
corresponding crown ether. In view of the easy availabilities
and binding capabilities of these cryptands, this approach
might be expected to be extendable to the construction of
mechanically interlocked structures, such as rotaxanes and
catenanes. Furthermore, one can envisage polymerization
of diacetylene components to generate unique π-conjugated
1
1
40.0 °C. H NMR (400 MHz, CDCl
H), 6.36 (s, 2 H, Ar-H), 4.56 (s, 4 H, –CH
H, α-OCH ), 3.85 (t, J = 4.0 Hz, 8 H, β-OCH
2
3
, 22 °C): δ = 6.50 (s, 4 H, Ar-
OH), 4.05 (d, J = 4.0 Hz,
), 3.73 (s, 8 H, γ-
, 22 °C): δ = 159.97,
43.30, 105.25, 100.89, 70.84, 69.60, 67.37, 65.10 ppm. MS (ESI):
2
8
2
13
2 3
OCH ) ppm. C NMR (100 MHz, CDCl
1
+
m/z (%) = 531.60 [M + Na] .
Synthesis of Compound 3: Sodium hydride (60% in mineral oil,
.19 g, 3.9 mmol) was added under N at 0 °C to a suspension of
0
2
compound 2 (0.76 g, 1.5 mmol) in dry THF (15 mL). The mixture
was stirred for 0.5 h. Propargyl bromide (80% in toluene, 1.1 mL,
–1
1
.06 mmol) was added at 1 mLh . The reaction mixture was
polymer materials and mechanically interlocked polymers stirred for 1 h at 0 °C and for 4 d at room temperature. The excess
with π-conjugated backbones either by direct utilization of NaH was quenched with ice water, and the mixture was extracted
with ethyl acetate and CHCl
concentrated to give a yellow powder. This crude compound was
purified by column chromatography [SiO , ethyl acetate/CH Cl
:1, v/v] and solvent removal to give compound 3 (0.75 g, 86%) as
3 4
, combined, dried with MgSO , and
diacetylene-containing cryptand or after formation of inter-
locked structures. We now intend to explore these possibil-
ities.
2
2
2
1
1
a light yellow powder; m.p. 103.7–104.6 °C. H NMR (400 MHz,
CDCl , 22 °C): δ = 6.51 (s, 4 H, Ar-H), 6.44 (s, 2 H, Ar-H), 4.51
s, 4 H, benzyl-H), 4.13 (s, 4 H, α-CH ), 4.08 (d, J = 4.0 Hz, 8 H,
α-OCH ), 3.86 (d, J = 4.0 Hz, 8 H, β-OCH ), 3.73 (s, 8 H, γ-
OCH ), 2.45 (s, 2 H, –CϵCH) ppm. C NMR (100 MHz, CDCl
2 °C): δ = 159.98, 139.40, 106.50, 101.31, 79.60, 74.61, 71.33,
0.88, 69.57, 67.41, 56.88 ppm. MS (ESI): m/z (%) = 602.25 [M +
3
Experimental Section
(
2
2
2
General: Unless specified otherwise, all reagents were purchased
from commercial suppliers and used as received. THF was distilled
from sodium/acetophenone; CH
reactions were carried out under N
1
3
2
3
,
2
7
3
CN was distilled from CaH
2
. All
2
. Melting points were deter-
+
4 40
NH ] . C32H O10 (584.65): calcd. C 65.74, H 6.90; found C 65.70,
mined with an Electrothermal x-5 melting point apparatus and are
uncorrected. Thin-layer chromatography was performed on Qing-
Dao silica gel. NMR spectra were recorded at ambient temperature
with a Varian NMR system (400 MHz) with use of the deuterated
solvent as the lock and the residual solvent or TMS as the internal
reference. Low-resolution electrospray ionization mass spectra were
recorded with a Thermo Finnigan LCQ Deca XP Max LC/MSn
instrument. High-resolution electrospray ionization mass spectra
were recorded with a Bruker Apex IV FTMS instrument at Peking
University. Elemental analysis were obtained with a FlaskEA 1112
Series CHNS-O analyzer. MALDI-TOF MS were provided by
Nankai University. X-ray crystallographic analyses were performed
with a Bruker SMART APEX II machine.
H 7.10.
Synthesis of Compound 4: A solution of compound 3 (584.7 mg,
1.0 mmol) was slowly added under O at 45–50 °C to a solution of
Cu(OAc) ·H O (199.7 mg, 1.0 mmol) in dry CH CN (10 mL) and
2
2
2
3
CH Cl (40 mL). The solvent was then removed, and the crude
2
2
–
1
bluish solid was dissolved in aq. ammonia (0.5 molmL ) and ex-
tracted with CH Cl . After drying and removal of solvent, the
crude product was purified by column chromatography [SiO , ethyl
acetate/CH Cl 1:1, v/v] and the solvent was removed to give a light
yellow powder, which was recrystallized from CH OH to give com-
2
2
2
2
2
3
pound 4 (565.2 mg, 97%) as a white solid; m.p. 105.6–106.8 °C.
1
HNMR (400 MHz, CDCl , 22 °C): δ = 6.58 (s, 4 H, Ar-H), 6.30
3
(
(
s, 2 H, Ar-H), 4.50 (s, 4 H, benzyl-H), 4.23 (s, 4 H, α-CH
2
), 4.03
), 3.70 (s, 8 H,
, 22 °C): δ = 159.94,
Synthesis of Compound 1: A solution of tri(ethylene glycol) ditosyl-
s, 8 H, α-OCH
2
1
), 3.81 (t, J = 4.0 Hz, 8 H, β-OCH
2
ate (3.21 g, 7 mmol) and methyl 3,5-dihydroxybenzoate (1.18 g,
3
γ-OCH
1
5
2
) ppm. C NMR (100 MHz, CDCl
3
–
1
7
1
CH
mmol) in CH
00 °C to a suspension containing K
CN (75 mL). After the completion of the addition, the solution
3
CN (25 mL) was added at 1 mLh and at 90–
40.00, 106.85, 101.35, 75.78, 72.72, 70.99, 70.88, 69.86, 67.44,
2
CO (4.83 g, 35 mmol) in
3
+
4
8.53 ppm. MS (ESI): m/z (%) = 600.32 [M + NH ] . MALDI-
3
+
TOF-MS: m/z (%) calcd. for [M + Na] , 605.2363; found 605.2441.
was stirred at 90–100 °C for 2 d, allowed to cool, filtered, and con-
centrated to give a pale yellow, viscous oil. This crude compound
Synthesis of Compound 5: Pd/C (10%, 12 mg) was added to a solu-
tion of compound 4 (116.5 mg, 0.2 mmol) in ethyl acetate (10 mL).
The suspension was stirred under H at room temperature. After
2
24 h, TLC showed complete conversion to product. The catalyst
was removed by filtration and the filtrate was concentrated to give
a white oil. This crude compound was purified by column
was purified by column chromatography [SiO
:4, v/v]. After the solvent had been removed, the resulting pale
yellow solid was recrystallized from acetone to give compound 1
2 2 2 2
, CH Cl /Et O
1
[
9d]
(
0.53 g, 28%) as a white powder; m.p. 128.3–129.3 °C (ref.
31.2–133.2 °C). H NMR (400 MHz, CDCl
3
m.p.
, 22 °C): δ = 7.16 (s,
H, Ar-H), 6.68 (s, 2 H, Ar-H), 4.12 (t, J = 4.0 Hz, 8 H, α-OCH ),
.87 (s, 6 H, –COOMe), 3.86 (t, J = 4.0 Hz, 8 H, β-OCH ), 3.74
) ppm. 13C NMR (100 MHz, CDCl
, 22 °C): δ = powder; m.p. 88.2–89.4 °C. H NMR (400 MHz, CDCl
1
1
4
3
2
2 2 2
chromatography [SiO , ethyl acetate/CH Cl 1:1, v/v] and the sol-
2
vent was removed to give compound 5 (109 mg, 93%) as a white
1
(s, 8 H, γ-OCH
2
3
3
, 22 °C): δ
Eur. J. Org. Chem. 2010, 1904–1911
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1909

L. Jiang et al.
FULL PAPER
=
6.42 (s, 4 H, Ar-H), 6.27 (s, 2 H, Ar-H), 4.30 (s, 4 H, benzyl-H),
.95 (s, 8 H, α-OCH ), 3.79 (t, J = 4.0 Hz, 8 H, β-OCH ), 3.70 (s,
H, γ-OCH ), 3.27 (t, J = 8.0 Hz, 4 H, α-CH ), 1.46 (t, J = 4.0 Hz,
H, β-CH
, 22 °C): δ = 159.81, 140.76, 106.73, 100.79, 72.77, 70.96,
9.70, 68.80, 67.25, 29.25, 24.86 ppm. MS (ESI): m/z (%) = 608.44
D. Sobransingh, A. E. Kaifer, Angew. Chem. Int. Ed. 2004, 43,
5496–5499; d) K. Moon, A. E. Kaifer, Org. Lett. 2004, 6, 185–
3
8
4
2
2
188.
2
2
3
) ppm. 1 C NMR (100 MHz,
[4] a) D. Jokic, Z. Asfari, J. Weiss, Org. Lett. 2002, 4, 2129–2132;
b) L. Baldini, P. Ballester, A. Casnati, R. M. Gomila, C. A.
Hunter, F. Sansone, R. Ungaro, J. Am. Chem. Soc. 2003, 125,
2
), 1.13 (s, 4 H, γ-CH
2
CDCl
6
3
1
4181–14189; c) A. Arduini, R. Ferdani, A. Pochini, A. Secchi,
+
+
[M + NH
4
] . HR-MS (ESI): calcd. for [M + H] 591.3169; found
F. Ugozzoli, Angew. Chem. Int. Ed. 2000, 39, 3453–3456; d) A.
Arduini, F. Ciesa, M. Fragassi, A. Pochini, A. Secchi, Angew.
Chem. Int. Ed. 2005, 44, 278–281; e) Q.-Y. Chen, C.-F. Chen,
Eur. J. Org. Chem. 2005, 2468–2472.
+
591.3162; calcd. for [M + Na] 613.2989; found 613.2978.
CCDC-752976 (for 4 ·6), -752977 (for 5 ·6), -752978 (for 3),
752979 (for 4) and -752980 (for 5) contain the supplementary crys-
2
2
-
[
5] a) Y. Liu, Y.-L. Zhao, H.-Y. Zhang, H.-B. Song, Angew. Chem.
Int. Ed. 2003, 42, 3260–3263; b) Y. Liu, L. Li, H.-Y. Zhang,
Y.-L. Zhao, X. Wu, Macromolecules 2002, 35, 9934–9938; c) Y.
Liu, Y.-L. Zhao, H.-Y. Zhang, E.-C. Yang, X.-D. Guan, J. Org.
Chem. 2004, 69, 3383–3390; d) Y. Liu, Y.-L. Zhao, Y. Chen,
D.-S. Guo, Org. Biomol. Chem. 2005, 3, 584–591; e) Y. Liu, S.-
H. Song, Y. Chen, Y.-L. Zhao, Y.-W. Yang, Chem. Commun.
tallographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/conts/retrieving.html or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB21EZ, UK [Fax: (+44)1223-336-033; or E-mail: deposit-
@
ccdc.cam.ac.uk].
Supporting Information (see also the footnote on the first page of
this article): 1H NMR and C NMR spectra of all compounds,
low-resolution electrospray ionization mass spectra of complexes
2
005, 1702–1704.
6] a) X.-Z. Zhu, C.-F. Chen, J. Am. Chem. Soc. 2005, 127, 13158–
3159; b) Y. Liu, C.-C. You, H.-Y. Zhang, S.-Z. Kang, C.-F.
13
[
1
4
2
·6 and 5
2
·6, and crystal data and structure refinement data for
Zhu, C. Wang, Nano Lett. 2001, 1, 613–616; c) K. Zhu, S. Li,
F. Wang, F. Huang, J. Org. Chem. 2009, 74, 1322–1328.
the compounds and complexes.
[
7] a) W. S. Bryant, J. W. Jones, P. E. Mason, I. Guzei, A. L.
Rheingold, F. R. Fronczek, D. S. Nagvekar, H. W. Gibson,
Org. Lett. 1999, 1, 1001–1004; b) F. Huang, L. Zhou, J. W.
Jones, H. W. Gibson, M. Ashraf-Khorassani, Chem. Commun.
Acknowledgments
2
004, 2670–2671; c) F. Huang, C. Slebodnick, K. A. Switek,
We thank the National Natural Science Foundation of China
H. W. Gibson, Chem. Commun. 2006, 1929–1931; d) F. Huang,
K. A. Switek, H. W. Gibson, Chem. Commun. 2005, 3655–
(number 20672038) and Natural Science Foundation of Guang-
dong Province of China (number 8151063101000015) for financial
support.
3
657; e) F. Huang, H. W. Gibson, W. S. Bryant, D. S. Nagvekar,
F. R. Fronczek, J. Am. Chem. Soc. 2003, 125, 9367–9371; f) F.
Huang, F. R. Fronczek, H. W. Gibson, J. Am. Chem. Soc. 2003,
1
25, 9272–9273; g) M. Liu, S. Li, M. Zhang, Q. Zhou, F. Wang,
M. Hu, F. R. Fronczek, N. Li, F. Huang, Org. Biomol. Chem.
009, 7, 1288–1291; h) F. Huang, K. A. Switek, L. N. Zakh-
[
1] J. F. Stoddart, Chem. Soc. Rev. 2009, 38, 1802–1820; M. R.
Francisco, J. F. Stoddart, Chem. Rev. 1999, 99, 1643–1663; J. D.
Crowley, S. M. Goldup, A.-L. Lee, D. A. Leigh, R. T. McBur-
ney, Chem. Soc. Rev. 2009, 38, 1530–1541; C.-F. Lee, D. A.
Leigh, R. G. Pritchard, D. Schultz, S. J. Teat, G. A. Timco,
R. E. P. Winpenny, Nature 2009, 458, 314–318; F. Huang,
H. W. Gibson, Prog. Polym. Sci. 2005, 30, 982–1018; L. Jiang,
J. Okano, A. Orita, J. Otera, Angew. Chem. Int. Ed. 2004, 116,
2
arov, F. R. Fronczek, C. Slebodnick, M. Lam, J. A. Golen,
W. S. Bryant, P. Mason, A. L. Rheingold, M. Ashraf-Khoras-
sani, H. W. Gibson, J. Org. Chem. 2005, 70, 3231–3241; i) F.
Huang, C. Slebodnick, K. A. Switek, H. W. Gibson, Tetrahe-
dron 2007, 63, 2829–2839; j) F. Huang, C. Slebodnick, E. J.
Mahan, H. W. Gibson, Tetrahedron 2007, 63, 2875–2881; k) X.
Zhang, C. Zhai, N. Li, M. Liu, S. Li, K. Zhu, J. Zhang, F.
Huang, H. W. Gibson, Tetrahedron Lett. 2007, 48, 7537–7541;
l) F. Wang, Q. Zhou, K. Zhu, S. Li, C. Wang, M. Liu, N. Li,
F. R. Fronczek, F. Huang, Tetrahedron 2009, 65, 1488–1494; m)
J. G. Maxwell, P. J. Tyrone, R. J. Martin, T. Peter, Z. P. Chen, J.
Chem. Soc. Perkin Trans. 1 1998, 1945–1957.
2173–2176; D. A. Leigh, F. Zerbetto, E. R. Kay, Angew. Chem.
Int. Ed. 2007, 46, 72–191; M. J. Frampton, H. L. Anderson,
Angew. Chem. Int. Ed. 2007, 46, 1028–1064; H. Tian, Q.-C.
Wang, Chem. Soc. Rev. 2007, 36, 361–374; C. D. Meyer, C. S.
Joiner, J. F. Stoddart, Chem. Soc. Rev. 2007, 36, 1705–1723; C.
Zhang, S. Li, J. Zhang, K. Zhu, N. Li, F. Huang, Org. Lett.
2
007, 9, 5553–5556; S.-Y. Hsueh, C.-C. Lai, Y.-H. Liu, S.-M.
[
8] a) H. W. Gibson, H. Wang, C. Slebodnick, J. Merola, W. S.
Kassel, A. L. Rheingold, J. Org. Chem. 2007, 72, 3381–3393;
b) A. M.-P. Pederson, E. M. Ward, D. V. Schoonover, C. Sle-
bodnick, H. W. Gibson, J. Org. Chem. 2008, 73, 9094–9101.
9] a) G. Rogez, B. F. Ribera, A. Credi, R. Ballardini, M. T. Gan-
dolfi, V. Balzani, Y. Liu, B. H. Northrop, J. F. Stoddart, J. Am.
Chem. Soc. 2007, 129, 4633–4642; b) L. Fang, M. Hmadeh, J.
Wu, M. A. Olson, J. M. Spruell, A. Trabolsi, Y.-W. Yang, M.
Elhabiri, A.-M. Albrecht-Gary, J. F. Stoddart, J. Am. Chem.
Soc. 2009, 131, 7126–7134; c) V. Balzani, A. Credi, F. M.
Raymo, J. F. Stoddart, Angew. Chem. Int. Ed. 2000, 39, 3348–
Peng, S.-H. Chiu, Angew. Chem. Int. Ed. 2007, 46, 2013–2017;
J.-M. Zhao, Q.-S. Zong, T. Han, J.-F. Xiang, C.-F. Chen, J.
Org. Chem. 2008, 73, 6800–6806; C.-F. Lin, Y.-H. Liu, C.-C.
Lai, S.-M. Peng, S.-H. Chiu, Chem. Eur. J. 2006, 12, 4594–
[
4
599; A. F. M. Kilbinger, S. J. Cantrill, A. W. Waltman, M. W.
Day, R. H. Grubbs, Angew. Chem. Int. Ed. 2003, 42, 3281–
285; P. R. Ashton, R. Ballardini, V. Balzani, M. Belohradsky,
3
M. T. Gandolfi, D. Philp, L. Prodi, F. M. Raymo, M. V. Redd-
ington, N. Spencer, J. F. Stoddart, M. Venturi, D. J. Williams,
J. Am. Chem. Soc. 1996, 118, 4931–4951.
[2] a) F. Huang, F. R. Fronczekb, H. W. Gibson, Chem. Commun.
3
391; d) Y. Delaviz, J. S. Merola, M. A. G. Berg, H. W. Gibson,
2003, 1480–1481; b) F. Huang, M. Lam, E. J. Mahan, A. L.
J. Org. Chem. 1995, 60, 516–522; e) Y. Delaviz, H. W. Gibson,
Macromolecules 1992, 25, 18–20; f) H. W. Gibson, D. S.
Nagvekar, Can. J. Chem. 1997, 75, 1375–1384.
Rheingold, H. W. Gibson, Chem. Commun. 2005, 3268–3270;
c) F. Huang, H. W. Gibson, Chem. Commun. 2005, 1696–1698;
d) J. D. Badjic, V. Balzani, A. Credi, S. Silvi, J. F. Stoddart,
Science 2004, 303, 1845–1849; e) J. D. Badjic, S. J. Cantrill, J. F.
Stoddart, J. Am. Chem. Soc. 2004, 126, 2288–2289; f) T. Han,
C.-F. Chen, Org. Lett. 2006, 8, 1069–1072.
[
10] a) O. S. Miljanic, W. R. Dichtel, S. I. Khan, S. Mortezaei, J. R.
Heath, J. F. Stoddart, J. Am. Chem. Soc. 2007, 129, 8236–8246;
b) O. S. Miljanic, W. R. Dichtel, S. Mortezaei, J. F. Stoddart,
Org. Lett. 2006, 8, 4835–4838; c) U. Meissner, B. Meissner,
H. A. Staab, Angew. Chem. Int. Ed. Engl. 1973, 12, 916–918.
[
3] a) L. Yuan, R. Wang, D. H. Macartney, J. Org. Chem. 2007,
72, 4539–4542; b) S. Y. Jon, N. Selvapalam, D. H. Oh, J.-K.
Kang, S.-Y. Kim, Y. J. Jeon, J. W. Lee, K. Kim, J. Am. Chem.
Soc. 2003, 125, 10186–10187; c) M. Kwangyul, J. Grindstaff,
[11] G. Weber, Molecular Biophysics (Eds.: B. Pullman, M.
Weissbluth), Academic Press, New York, 1965, pp. 369–397; H.
1910
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1904–1911

Novel Cryptands Based on Bis(m-phenylene)-26-crown-8
Tsukube, H. Furuta, A. Odani, Y. Takeda, Y. Kudo, Y. Inoue,
Y. Liu, H. Sakamoto, K. Kimura, in: Comprehensive Supra-
molecular Chemistry (Eds.: J. L Atwood, J. E. D. Davies, D. D.
MacNicol, F. Vögtle, J.-M. Lehn), Pergamon, New York, 1996,
vol. 8, pp. 436–439.
dently. The value of the slope is –457, which equals the values
of both –2K and 2K – K simultaneously. We calculated the
2
2
1
errors of the association constants on the basis of the error of
the slope; see: a) K. A. Connors, Binding Constants, Wiley,
New York, 1987; b) ref.[
13]
[
12] a) C. Gong, P. B. Balanda, H. W. Gibson, Macromolecules
2
[15] The crystal data for complex 5 ·6 are imperfect. We tried our
13a]
[7f]
1
998, 31, 5278–5289; b) ref.[ ; c) ref.
.
best, including growing crystals in different solvent systems and
performing data collection on different single crystals at low
temperature, but no better data set could be obtained. Al-
though this data set is not good, the framework can be clearly
solved and the crystallographic data strongly support the spec-
troscopic characterization.
[
13] a) F. Huang, P. Gantzel, D. S. Nagvekar, A. L. Rheingold,
H. W. Gibson, Tetrahedron Lett. 2006, 47, 7841–7844; b) P.-N.
Cheng, C.-F. Lin, Y.-H. Liu, C.-C. Lai, S.-M. Peng, S.-H. Chiu,
Org. Lett. 2006, 8, 435–438.
[
14] In a system possessing two identical binding sites for its com-
plementary partner, with association constants K
1
and K
2
,
Received: November 11, 2009
Published Online: February 16, 2010
respectively, K = 4K if the binding sites operate indepen-
1
2
Eur. J. Org. Chem. 2010, 1904–1911
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1911