Synthesis of a bis(1,2,3-phenylene) cryptand and its dual-response binding to paraquat and diquat

Article abstract of DOI:10.1002/ejoc.201001034

A bis(1,2,3-phenylene) cryptand has been synthesized and used to prepare 1:1 complexes with paraquat and diquat, with association constants of 2.2 × 10³ M^-1 and 3.7 × 10³ M ^-1, respectively, in CHCl₃/

Full text of DOI:10.1002/ejoc.201001034

FULL PAPER
DOI: 10.1002/ejoc.201001034
Synthesis of a Bis(1,2,3-phenylene) Cryptand and Its Dual-Response Binding to
Paraquat and Diquat
Mingming Zhang,[a] Bo Zheng,[a] Binyuan Xia,[a] Kelong Zhu,[a] Chuande Wu,[a] and
Feihe Huang*[a]
Keywords: Cryptands / Crown compounds / Host-guest systems / Taco complexes / Controllable assembly
A bis(1,2,3-phenylene) cryptand has been synthesized and
never been found before in cryptand/paraquat complexes.
Furthermore, its binding to paraquat and diquat in solution
can be switched off (and back on) by addition of acid or K+
(and then base or 18-crown-6).
used to prepare 1:1 complexes with paraquat and diquat,
–1
with association constants of 2.2ϫ103
M M ,
–1 and 3.7ϫ103
respectively, in CHCl3/CH3CN (1:1). In the solid state this
cryptand forms a taco complex with paraquat, which has
previously reported cryptands are bis(1,3,5-phenylene) or
bis(1,2,4-phenylene) ones;[6–11] no bis(1,2,3-phenylene) ana-
logues had been reported until now. We became interested
in preparing bis(1,2,3-phenylene) cryptands and studying
their complexation with paraquat in order to investigate
how the differences in the positions of the ether chains on
the two phenyl rings affect the binding of bisphenylene
cryptands to paraquat. Here we report the synthesis of the
bis(1,2,3-phenylene) cryptand 1 (Scheme 1) and its dual-re-
sponsive binding to paraquat 3 and diquat 4.[12]
Introduction
The design and preparation of novel hosts featuring
strong host–guest interactions and controllable binding
properties is a hot topic in supramolecular chemistry, due
to their applications in the fabrication of molecular
switches,[1] molecular machines,[2] drug delivery materials,[3]
supramolecular polymers,[4] and other interesting host–
guest systems.[5] Paraquat (N,NЈ-dimethyl-4,4Ј-bipyridi-
nium) and diquat (1,1Ј-ethylene-2,2Ј-bipyridinium) deriva-
tives are commonly used guests in supramolecular chemis-
try.[2h,6,7] Gibson et al. designed and synthesized crown
ether-based cryptand hosts for paraquat and diquat deriva-
tives for the efficient preparation of mechanically inter-
locked structures and large supramolecular systems from
small molecules with the aid of host–guest recognition mo-
tifs.[6a–6d,7] They showed that these cryptands can complex
paraquat and diquat derivatives much more strongly than
the corresponding simple crown ethers. Later, we demon-
strated that mechanically interlocked structures such as rot-
axanes[8] and catenanes[8c,9] could be constructed in high
yields with the aid of such cryptand/paraquat recognition
motifs and that supramolecular polymers[4d] could be fabri-
cated efficiently. Liu et al. developed an excellent one-pot
[2+3] clipping method to obtain a cryptand and a related
[2]rotaxane through sixfold imine bond formation.[10] Re-
cently, Jiang et al. demonstrated that diacetylene-containing
cryptands could be made with high yields through cop-
per(II)-mediated Eglinton coupling.[11] However, all of the
Results and Discussion
The design of the bis(1,2,3-phenylene) cryptand 1 was
inspired by the crystal structure of a taco complex 2aʛ3
formed
between
the
bis(m-phenylene)-32-crown-10
(BMP32C10) derivative 2a and paraquat 3 (Scheme 1).[6a]
Note from the crystal structure of 2aʛ3 that an F atom
of the PF6 counterion is hydrogen-bonded to the two β-
pyridinium hydrogen atoms of 3. On the basis of this obser-
vation we designed the bis(1,2,3-phenylene) cryptand 1 with
a hydrogen-bond acceptor site – the pyridyl nitrogen atom –
in approximately the right location for interaction with the
two β-pyridinium hydrogen atoms of 3. The cryptand 1 was
synthesized from the commercially available starting mate-
rial propyl gallate in seven steps and in reasonable yields
(Scheme 1). Complexation between the cryptand 1 and
paraquat 3 or diquat 4 was then studied. When equimolar
(8.00 mm) CHCl3/CH3CN (1:1 v:v) solutions of 1 and either
3 or 4 were prepared, a bright yellow color appeared as a
result of charge-transfer interactions between the electron-
rich aromatic rings of 1 and the electron-poor pyridinium
rings of 3 or 4.
[a] Department of Chemistry, Zhejiang University,
Hangzhou 310027, P. R. China
Fax: +86-571-8795-3189
E-mail: fhuang@zju.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001034.
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Dual-Response Binding in a Bis(1,2,3-phenylene) Cryptand
Scheme 1. Synthesis of the bis(1,2,3-phenylene) cryptand 1, together with the chemical structures of the bis(m-phenylene)-32-crown-10
derivatives 2a and 2b, paraquat 3, and diquat 4.
Job plots[13] based on UV/Vis spectroscopic absorbance c, and d) are formed between the hydrogen atoms on the
data for the charge-transfer bands (λ = 403 nm) demon- same side of paraquat 3 with oxygen or nitrogen atoms on
strated that the complexes of 1 with 3 or 4 in solution were the cryptand 1. Most notably, in accordance with our de-
each of 1:1 stoichiometry. It was previously reported that sign, a β-pyridinium hydrogen of the guest 3 is directly hy-
the complex formed in solution between BMP32C10 (2b, drogen-bonded to the pyridine nitrogen atom of the host in
Scheme 1) and 3 was also of 1:1 stoichiometry.[6c] The asso- 1ʛ3. The crystals of the 1ʛ3 complex have a yellow color
ciation constants (Ka) of the complexes 1ʛ3, 1ʛ4, and due to charge-transfer interactions between the electron-
2bʛ3 in CHCl3/CH3CN (1:1 v:v) were determined by ex- rich aromatic rings of 1 and the electron-poor pyridinium
amination of the charge-transfer bands of the complexes rings of 3. Interestingly, an aromatic edge-to-face interac-
by UV/Vis spectroscopy and by a titration method to be tion (e) between a β-pyridinium hydrogen and the pyridine
2.2(Ϯ0.5)ϫ103 m–1, 3.7(Ϯ1.0)ϫ103 m–1, and 917(Ϯ70) moiety on the cryptand 1 is found in the solid structure
m–1, respectively. Therefore, an increase in association con-
stants was observed on going from the crown ether-based
complex 2bʛ3 to the cryptand-based complex 1ʛ3.
The electrospray ionization mass spectra also confirmed
the 1:1 complexation between the cryptand 1 and paraquat
(3) or diquat (4). Peaks were found at m/z 458.8 (100%) and
1062.4 (12.5%) for 1ʛ3 and at m/z 457.7 (100%) and 1059.9
(21.5%) for 1ʛ4, corresponding to [1ʛ3 – 2PF6]2+, [1ʛ3 –
PF6]+, [1ʛ4 – 2PF6]2+, and [1ʛ4 – PF6]+, respectively.
The 1:1 stoichiometry of the cryptand 1 and paraquat 3
was further confirmed by X-ray diffraction analysis of a
yellow single crystal grown by vapor diffusion of diisopro-
pyl ether into a CHCl3/CH3CN (1:1 v:v) solution of 1 and
Figure 1. A ball-and-stick view of the X-ray crystal structure of
1ʛ3. PF6 counterions, solvent molecules, and hydrogens other
than those involved in hydrogen bonding between the cryptand 1
3. The 1ʛ3 complex has a taco complex geometry (Fig-
–
ure 1),[14] never found before in cryptand/paraquat com-
and paraquat 3 are omitted for clarity. Hydrogen bond parameters:
H···O (N) distance [Å], C–H···O (N) angle [°], C···O (N) distance
[Å] a) 2.50, 156, 3.37; b) 2.57, 118, 3.12; c) 2.46, 155, 3.32; d) 2.50,
157, 3.40. The C–H···π edge-to-face interaction e is defined by an
plexes, which have previously all been of the inclusion or
pseudorotaxane types.[6,7a–7c,8–11] The complex is stabilized
by hydrogen bonding, charge transfer, and aromatic edge-
to-face π-stacking interactions in the solid state (Figure 1).
H···pyridine centroid distance [Å] of 2.69 and
a
C–H···
The crystal structure shows that four hydrogen bonds (a, b, centroid angle [°] of 155.
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FULL PAPER
(Figure 1), increasing the host–guest interactions between 1 paraquat 3 returned almost to their uncomplexed value
and 3. (spectra a and c in Figure 2), indicating that the complex-
Further investigation of the complexation between 1 and ation between the cryptand host 1 and paraquat 3 was es-
3 or 4 was carried out by proton NMR spectroscopy (spec- sentially totally quenched; consistently with this, the color
tra a, b, and e in Figure 2 and Figure S21 in the Supporting of the solution changed from yellow to colorless. After ad-
Information). The complexation systems 1ʛ3 and 1ʛ4 are dition of triethylamine (6 drops) to this solution, complex-
fast-exchange on the proton NMR timescale. A significant ation between 1 and 3 was recovered; a large change in the
upfield shift was observed for the H11 β-pyridinium protons chemical shift corresponding to H11 of 3 was again ob-
of paraquat 3, whereas no obvious chemical shift changes served (see spectra b and d of Figure 2).[15] The color of the
were observed after complexation for the H10 α-pyridinium solution changed to yellow again. Additionally, the H8 and
protons or the H12 N-methyl protons of 3 (spectra a and b H9 pyridyl protons and the H7 methylene protons of 1 had
in Figure 2). This is noteworthy because obvious chemical clearly shifted downfield after addition of trifluoroacetic
shift changes after complexation have usually been seen for acid (spectra b and c in Figure 2), indicating that the pyr-
H10 α-pyridinium protons in previously reported cryptand/ idyl nitrogen atom of 1 was protonated.
paraquat complexes.[6,7a–7c,8–11] The H6 aromatic protons,
On the other hand, from crown ether 2a to the cryptand
the H5 benzyl protons, and the H1 α-ethylenoxy protons 1, the introduction of a seven-atom third chain divides the
of 1 moved upfield after complexation (spectra b and e in BMP32C10 cavity into two asymmetric 24-crown-8 cavities
Figure 2). Other protons of the cryptand 1 did not undergo (Scheme 1). When K+ is added, the cryptand 1 should form
obvious chemical shift changes after complexation (spec- a more stable 1:2 complex with K+, which can cause the
tra b and e in Figure 2). Chemical shift changes could also complex between the cryptand 1 and paraquat 3 to disas-
be observed for the complexation system between the cryp- semble. Later, when enough 18-crown-6 (18C6) is added to
tand 1 and diquat 4 (Figure S21 in the Supporting Infor- trap the K+, the complex 1ʛ3 can reform. This was also
mation).
confirmed by proton NMR experiments (Figure 3). When
KPF6 (2 molar equiv.) was added to an equimolar solution
of 1 and 3 (8.00 mm) in CDCl3/CD3CN (1:1), the chemical
shifts of the paraquat 3 protons returned to their uncom-
plexed values (spectra a and c in Figure 3) and correspond-
ingly the yellow color of the solution totally disappeared,
indicating the total dissociation of the 1ʛ3 complex. How-
ever, when 18C6 (2 mol-equiv.) was subsequently added,
chemical shift changes of the protons on 3 were again ob-
served (see spectra b and d of Figure 3) and correspond-
ingly the yellow color of the solution recovered, indicating
the reformation of the 1ʛ3 complex.[15]
1
Figure 2. Partial H NMR spectra (400 MHz, CDCl3/CD3CN 1:1,
295 K) of: a) 3, b) 1 and 3 (8.00 mm), c) a solution of trifluoroacetic
acid (3 drops) and 1 and 3 (8.00 mm, 0.5 mL), d) a solution of tri-
fluoroacetic acid (3 drops), triethylamine (6 drops), and 1 and 3
(8.00 mm, 0.5 mL), and e) 1.
We next turned to the control of the binding between the
cryptand 1 and paraquat 3. From crown ether 2b to cryp-
tand 1, a chain containing seven atoms, a pyridyl nitrogen
atom located in its center, was introduced into the crown
ether 2a to form the cryptand 1. The introduced pyridyl
nitrogen atom can be protonated by addition of acid, which
will cause the complex to disassemble. Later, when enough
base is added to deprotonate the pyridinium moiety com-
pletely, the complex 1ʛ3 can form again.[7a] This was con-
firmed by proton NMR experiments (Figure 2). When tri-
fluoroacetic acid (3 drops) was added to 1 and 3 (each
1
Figure 3. Partial H NMR spectra (400 MHz, CDCl3/CD3CN 1:1,
295 K) of: a) 3, b) 1 and 3 (8.00 mm), c) 1 and 3 (8.00 mm) and
KPF6 (16.0 mm), d) 1 and 3 (8.00 mm), KPF6 (16.0 mm) and 18C6
(16.0 mm), and e) 1.
Similarly, the binding of the cryptand 1 to diquat 4 in
8.00 mm) in CDCl3/CD3CN (1:1, 0.5 mL), the chemical solution also could be switched off (and back on) by ad-
shift corresponding to the H11 β-pyridinium protons of dition of acid or K+ (and then base or 18C6).
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Dual-Response Binding in a Bis(1,2,3-phenylene) Cryptand
50.0 mmol) were placed in a 500 mL round-bottomed flask. The
flask was evacuated and then nitrogen was introduced. After this
process had been carried out three times, CH3CN (250 mL) was
added. The solution was stirred mechanically at reflux for 24 h.
The mixture was then filtered and the filtrate was concentrated to
give 6, which was used in the next step without further purification.
Conclusions
In summary, we have synthesized a novel bis(1,2,3-phen-
ylene) cryptand and studied its dual-response binding to
paraquat and diquat. We found that the cryptand 1 forms
a taco complex with paraquat 3 in the solid state. More
importantly, we demonstrated that the complexation be-
tween the cryptand 1 and paraquat 3 or diquat 4 could be
controlled either by changing the solution pH or by ad-
dition of small molecules such as KPF6 and 18C6. This
dual-responsive host–guest binding property is a unique
feature of the bis(1,2,3-phenylene) cryptand 1 in relation to
previously reported bis(1,3,5-phenylene) and bis(1,2,4-
phenylene) cryptands. The cryptand 1 can be used in ef-
ficient taco-complex-templated syntheses of mechanically
interlocked structures such as rotaxanes and catenanes[8c]
and its dual-response binding to paraquat and diquat could
be employable in the fabrication of advanced functional
supramolecular systems such as molecular switches and
molecular machines.
The unpurified 6 (25.6 g, 39.0 mmol) and p-toluenesulfonyl chlo-
ride (19.1 g, 100 mmol) were dissolved in CH2Cl2 (400 mL). Trieth-
ylamine (14.2 mL, 100 mmol) was added dropwise to the solution.
The whole mixture was stirred mechanically for 3 h at 6 °C and for
another 24 h at room temperature. When the reaction was com-
plete, the mixture was washed with brine (200 mLϫ3). The aque-
ous layer was separated and extracted with CH2Cl2 (200 mLϫ3).
The organic phase was combined, dried with anhydrous Na2SO4,
and concentrated. The residue was purified by flash column
chromatography (ethyl acetate/petroleum ether 2:3) to give 7
(13.2 g, 68.5%) as a yellow oil. 1H NMR (400 MHz, CDCl3,
295 K): δ = 7.77 (d, J = 7.0 Hz, 4 H, Ar-H), 7.48 (d, J = 7.0 Hz, 2
H, Ar-H), 7.26–7.32 (m, 9 H, Ar-H), 5.09 (s, 2 H, benzyl-H), 4.24
(t, J = 7.4 Hz, 2 H, α-CH2), 4.16 (t, J = 4.8 Hz, 4 H, α-OCH2),
4.12 (t, J = 4.8 Hz, 4 H, –CH2OTs), 3.84 (t, J = 5.0 Hz, 4 H, β-
OCH2), 3.68 (t, J = 5.0 Hz, 4 H, –CH2CH2OTs), 3.63 (t, J = 5.0 Hz,
4 H, γ-OCH2), 3.59 (t, J = 5.0 Hz, 4 H, –CH2OCH2CH2OTs), 3.54
(m, 8 H, δ-OCH2), 2.42 (s, 6 H, Ts-H), 1.76 (m, 2 H, β-CH2), 1.00
(t, J = 7.2 Hz, 3 H, γ-CH3) ppm. 13C NMR (100 MHz, CDCl3,
295 K): δ = 166.1, 152.4, 144.7, 141.8, 137.6, 132.8, 129.7, 128.1,
125.5, 108.5, 74.7, 70.6, 69.5, 69.2, 68.6, 66.6, 22.0, 21.6, 10.5 ppm.
LRESI-MS: m/z (%) = 985.3 (100) [7 + Na]+. HRESI-MS: calcd.
for C47H62NaO17S2 [7 + Na]+ 985.3321; found 985.3323, error
0.2 ppm.
Experimental Section
General: All reagents were purchased from commercial suppliers
and used as received. BMP32C10 (2b), BMP32C10 diol (2a),[16] and
(2,6-pyridinediyl)bismethylene ditosylate[17] were synthesized by
published literature procedures. NMR spectra were recorded with
a Bruker Advance DMX 500 spectrophotometer or a Bruker Ad-
vance DMX 400 spectrophotometer with use of the deuterated sol-
vent as the lock and the residual solvent or TMS as the internal
reference. Low-resolution electrospray ionization mass spectra were
recorded with a Bruker Esquire 3000 Plus spectrometer. High-reso-
lution mass spectrometry experiments were performed with a
Bruker Daltonics Apex III spectrometer. The high-resolution elec-
tron impact (HREI) mass spectrum of 5 was obtained with a GCT
Premier CAB170 mass spectrometer. CCDC-773275 (1ʛ3) con-
tains the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Synthesis of the Crown Ether 8: K2CO3 (2.76 g, 20.0 mmol), KPF6
(1.84 g, 10.0 mmol), and CH3CN (350 mL) were placed in a
1000 mL round-bottomed flask. The flask was evacuated and then
nitrogen was introduced. The flask was heated and a CH3CN solu-
tion (50.0 mL) of 7 (1.81 g, 1.88 mmol) and 5 (0.570 g, 1.88 mmol)
was added at a speed of 1.00 mLh–1 when the solution in the flask
began to reflux. After the solution had been completely added, the
mixture was stirred at reflux for a further seven days. The solution
was filtered and concentrated to give a pale yellow crude product,
which was purified by flash column chromatography (ethyl acetate/
petroleum ether 1:1) to give 8 (0.800 g, 52.3%) as a white solid;
Synthesis of 5: KHCO3 (7.50 g, 75.0 mmol) was cooled in an ice
bath under nitrogen.
1
m.p. 79.6–81.1 °C. H NMR (400 MHz, CD3COCD3, 295 K): δ =
A solution of propyl gallate (10.6 g,
7.44 (d, J = 7.0 Hz, 4 H, Ar-H), 7.17–7.21 (m, 8 H, Ar-H), 7.07–
7.11 (m, 2 H, Ar-H), 4.94 (s, 4 H, benzyl-H), 4.16 (t, J = 7.0 Hz, 4
H, α-CH2), 4.05 (t, J = 4.0 Hz, 8 H, α-OCH2), 3.76 (t, J = 4.0 Hz,
8 H, β-OCH2), 3.55–3.58 (m, 8 H, γ-OCH2), 3.50–3.54 (m, 8 H, δ-
OCH2), 1.68–1.73 (m, 4 H, β-CH2), 0.95 (t, J = 7.2 Hz, 6 H, γ-
CH3) ppm. 13C NMR (100 MHz, CD3COCD3, 295 K): δ = 165.3,
152.3, 128.5, 127.7, 125.5, 108.1, 74.4, 70.1, 69.3, 68.6, 66.1, 59.6,
21.8, 19.8, 13.5, 9.8 ppm. LRESI-MS: m/z (%) = 943.7 (100) [8 +
Na]+, 959.2 (18%) [8 + K]+. HRESI-MS: calcd. for C50H64NaO16
[8 + Na]+ 943.4087; found 943.4066, error –2.2 ppm.
50.0 mmol) in CH3CN (75.0 mL) was added dropwise. Benzyl bro-
mide (8.50 g, 50.0 mmol) was then added, and the reaction mixture
was allowed to warm to room temperature. After 16 h, the solvent
was removed in vacuo. The residue was dissolved in ethyl acetate
and water. The aqueous layer was separated and extracted with
ethyl acetate (100 mLϫ3). The organic layers were combined,
washed with brine, dried with anhydrous Na2SO4, and concen-
trated under reduced pressure to afford a dark oil, which was puri-
fied by flash column chromatography (ethyl acetate/petroleum
ether 8:100 followed by ethyl acetate/petroleum ether 15:100) to
give 5 (11.1 g, 73.1%) as a white solid; m.p. 109.3–110.7 °C. 1H
NMR (400 MHz, CDCl3, 295 K): δ = 7.40 (s, 5 H, Ar-H), 7.22 (s,
2 H, Ar-H), 5.51 (s, 2 H, benzyl-H), 5.13 (s, 2 H, –OH), 4.24 (t, J
= 5.4 Hz, 2 H, α-CH2), 1.76 (m, 2 H, β-CH2), 1.02 (t, J = 5.4 Hz,
3 H, γ-CH3) ppm. 13C NMR (100 MHz, CDCl3, 295 K): δ = 166.8,
149.0, 137.2, 136.4, 128.8, 126.0, 109.6, 75.4, 66.9, 21.9, 10.4 ppm.
LRESI-MS: m/z (%) = 303.2 (100) [5 + H]+. HREI-MS: calcd. for
C17H18O5 [5]+ 302.1154; found 302.1143, error –3.6 ppm.
Synthesis of the Crown Ether 9: Pd/C (130 mg) and 8 (540 mg,
0.586 mmol) were placed in a 250 mL round-bottomed flask. The
flask was evacuated and then hydrogen was introduced. After this
process had been carried out three times, CHCl3/CH3OH (1:1 v/v,
170 mL) was added. The system was heated at 60 °C for 24 h. The
solution was filtered and concentrated to give a crude product,
which was purified by flash column chromatography (ethyl acetate/
methanol 10:1) to give 9 (396 mg, 91.2%) as a white solid; m.p.
1
Synthesis of 6 and 7: K2CO3 (13.8 g, 100 mmol), compound 5 89.0–90.7 °C. H NMR (400 MHz, CD3COCD3, 295 K): δ = 7.32
(6.05 g, 20.0 mmol), and tetraethylene glycol monotosylate (17.4 g,
(s, 4 H, Ar-H), 4.16–4.21 (m, 12 H, α-CH2 and α-OCH2), 3.82 (t,
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[2]
a) M. C. Jiménez, C. Dietrich-Buchecker, J.-P. Sauvage, Angew.
Chem. Int. Ed. 2000, 39, 3284–3287; b) V. Balzani, A. Credi,
F. M. Raymo, J. F. Stoddart, Angew. Chem. Int. Ed. 2000, 39,
3348–3391; c) A. Harada, Acc. Chem. Res. 2001, 34, 456–464;
d) K. Kim, Chem. Soc. Rev. 2002, 31, 96–107; e) Y. Liu, A. H.
Flood, J. F. Stoddart, J. Am. Chem. Soc. 2004, 126, 9150–9151;
f) J.-P. Sauvage, Chem. Commun. 2005, 1507–1510; g) S. J.
Loeb, Chem. Commun. 2005, 1511–1518; h) E. R. Kay, D. A.
Leigh, F. Zerbetto, Angew. Chem. Int. Ed. 2007, 46, 72–191; i)
B. Champin, P. Mobian, J.-P. Sauvage, Chem. Soc. Rev. 2007,
36, 358–366; j) H. Zheng, W. Zhou, J. Lv, X. Yin, Y. Li, H.
Liu, Y. Li, Chem. Eur. J. 2009, 15, 13253–13262; k) X. Ma, H.
Tian, Chem. Soc. Rev. 2010, 39, 70–80.
a) J. M. Benito, M. Gómez-García, G. O. Mellet, I. Baussanne,
J. Defaye, J. M. G. Fernández, J. Am. Chem. Soc. 2004, 126,
10355–10363; b) J. Zhang, P. X. Ma, Angew. Chem. Int. Ed.
2009, 48, 964–968.
a) P. L. Vidal, M. Billon, B. Divisia-Blohorn, G. Bidan, J. M.
Kern, J.-P. Sauvage, Chem. Commun. 1998, 629–630; b) W.
Ong, J. Grindstaff, D. Sobransingh, R. Toba, J. M. Quintela,
C. Peinador, A. E. Kaifer, J. Am. Chem. Soc. 2005, 127, 3353–
3361; c) F. Wang, B. Zheng, K. Zhu, Q. Zhou, C. Zhai, S. Li,
N. Li, F. Huang, Chem. Commun. 2009, 4375–4377; d) F.
Wang, J. Zhang, X. Ding, S. Dong, M. Liu, B. Zheng, S. Li,
L. Wu, Y. Yu, H. W. Gibson, F. Huang, Angew. Chem. Int. Ed.
2010, 49, 1090–1094.
a) C. R. Bondy, S. J. Loeb, Coord. Chem. Rev. 2003, 240, 77–
99; b) C. R. Bondy, P. A. Gale, S. J. Loeb, J. Am. Chem. Soc.
2004, 126, 5030–5031; c) Y. Liu, X. Zhang, L. M. Klivansky,
G. Koshkakaryan, Chem. Commun. 2007, 4773–4775; d) Y.
Ling, W. Wang, A. E. Kaifer, Chem. Commun. 2007, 610–612;
e) S. Gadde, E. K. Batchelor, J. P. Weiss, Y. Ling, A. E. Kaifer,
J. Am. Chem. Soc. 2008, 130, 17114–17119; f) S. Liu, A. D.
Shukla, S. Gadde, B. D. Wagner, A. E. Kaifer, L. Isaacs, Angew.
Chem. Int. Ed. 2008, 47, 2657–2660; g) J.-P. Collin, F. Durola,
J. Frey, V. Heitz, J.-P. Sauvage, C. Tock, Y. Trolez, Chem. Com-
mun. 2009, 1706–1708; h) L. K. Knight, V. N. Vukotic, E. Vil-
joen, C. B. Caputo, S. J. Loeb, Chem. Commun. 2009, 5585–
5587; i) V. D. Uzunova, C. Cullinane, K. Brix, W. M. Nau, A. I.
Day, Org. Biomol. Chem. 2010, 8, 2037–2042; j) J. Yin, C. Chi,
J. Wu, Org. Biomol. Chem. 2010, 8, 2594–2599.
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, F. R. Fronczek,
H. W. Gibson, J. Am. Chem. Soc. 2003, 125, 9272–9273; c) F.
Huang, H. W. Gibson, W. S. Bryant, D. S. Nagvekar, F. R.
Fronczek, J. Am. Chem. Soc. 2003, 125, 9367–9371; d) F. Hu-
ang, K. A. Switek, L. N. Zakharov, F. R. Fronczek, C. Slebod-
nick, M. Lam, J. A. Golen, W. S. Bryant, P. E. Mason, A. L.
Rheingold, M. Ashraf-Khorassani, H. W. Gibson, J. Org.
Chem. 2005, 70, 3231–3241; e) S. Li, K. Zhu, B. Zheng, X.
Wen, N. Li, F. Huang, Eur. J. Org. Chem. 2009, 1053–1057; f)
K. Zhu, S. Li, F. Wang, F. Huang, J. Org. Chem. 2009, 74,
1322–1328; g) S. Li, B. Zheng, F. Huang, L. N. Zakharov, C.
Slebodnick, A. L. Rheingold, H. W. Gibson, Sci. China, Ser. B
Chem. 2010, 53, 858–862; h) C. Li, Q. Xu, J. Li, F. Yao, X. Jia,
Org. Biomol. Chem. 2010, 8, 1568–1576; i) M. Zhang, K. Zhu,
F. Huang, Chem. Commun., DOI: 10.1039/c0cc02717k.
J = 4.0 Hz, 8 H, β-OCH2), 3.69 (t, J = 4.0 Hz, 8 H, γ-OCH2), 3.62–
3.64 (m, 8 H, δ-OCH2), 1.72–1.77 (m, 4 H, β-CH2), 1.00 (t, J =
7.2 Hz, 6 H, γ-CH3) ppm. 13C NMR (100 MHz, CDCl3, 295 K): δ
= 162.2, 144.4, 142.6, 120.5, 110.9, 70.7, 70.4, 69.9, 69.3, 66.3, 22.0,
10.4 ppm. LRESI-MS: m/z (%) = 758.4 (35) [9 + NH4]+, 763.3
(100) [9 + Na]+. HRESI-MS: calcd. for C36H52NaO16 [9 + Na]+
763.3148; found 763.3166, error 2.4 ppm.
Synthesis of the Cryptand 10: K2CO3 (552 mg, 4.00 mmol), KPF6
(184 mg, 1.00 mmol), and CH3CN (160 mL) were placed in a
500 mL round-bottomed flask under nitrogen.
A CH3CN
(50.0 mL) solution of 9 (300 mg, 0.400 mmol) and (2,6-pyridine-
diyl)bismethylene ditosylate (180 mg, 0.400 mmol) was added at a
speed of 1.00 mLh–1 at reflux. The mixture was then stirred at re-
flux for a further 5 d. The solution was filtered and concentrated
to give a crude product, which was purified by flash column
chromatography (ethyl acetate) to give 10 (179 mg, 58.1%) as a
white solid; m.p. 159.7–160.5 °C. 1H NMR (400 MHz, CDCl3,
295 K): δ = 7.91 (m, 3 H, pyridine-H), 7.28 (s, 4 H, Ar-H), 5.31 (s,
4 H, benzyl-H), 4.25 (t, J = 7.0 Hz, 4 H, α-CH2), 4.15–4.22 (m, 8
H, α-OCH2), 3.85–3.89 (m, 8 H, β-OCH2), 3.60–3.66 (m, 8 H, γ-
OCH2), 3.52–3.58 (m, 8 H, δ-OCH2), 1.74–1.81 (m, 4 H, β-CH2),
1.01 (t, J = 7.2 Hz, 6 H, γ-CH3) ppm. 13C NMR (125 MHz, CDCl3,
295 K): δ = 166.0, 157.3, 151.9, 141.9, 137.3, 125.4, 119.5, 107.9,
75.2, 70.5, 69.4, 68.6, 66.5, 29.5, 21.9, 10.3 ppm. LRESI-MS: m/z
(%) = 844.3 (30) [10 + H]+, 866.3 (100) [10 + Na]+. HRESI-MS:
calcd. for C43H57NNaO16 [10 + Na]+ 866.3570; found 866.3535,
error –4.0 ppm.
[3]
[4]
[5]
Synthesis of the Cryptand 1: LiAlH4 (230 mg, 6.06 mmol) was
placed in a 150 mL round-bottomed flask. Compound 10 (150 mg,
0.124 mmol) in anhydrous THF (20.0 mL) was added slowly. Water
was then added to quench the remaining LiAlH4. The reaction mix-
ture was filtered under vacuum and the filtrate was concentrated
to give a crude product, which was purified by flash column
chromatography (ethyl acetate/methanol 10:1) to give 1 (78.9 mg,
87.1%) as a white solid; m.p. 130.8–131.6 °C. 1H NMR (400 MHz,
CDCl3, 295 K): δ = 7.92 (m, 3 H, pyridinium-H), 6.47 (s, 4 H, Ar-
H), 5.22 (s, 4 H, benzyl-H), 4.45 (s, 4 H, α-CH2), 4.10 (br., 8 H, α-
OCH2), 3.83 (br., 8 H, β-OCH2), 3.60 (t, J = 4.4 Hz, 8 H, γ-OCH2),
3.50 (t, J = 4.4 Hz, 8 H, δ-OCH2) ppm. 13C NMR (125 MHz,
CDCl3, 295 K): δ = 157.9, 152.5, 137.9, 137.3, 136.4, 120.3, 104.9,
75.2, 70.8, 69.9, 68.8, 65.0 ppm. LRESI-MS: m/z (%) = 629.5 (35)
[1 + H – CH2C5H3NCH2]+, 732.7 (40) [1 + H]+, 754.7 (100) [1 +
Na]+, 770.6 (10) [1 + K]+. HRESI-MS: calcd. for C37H49NNaO14
[1 + Na]+ 754.3045; found 754.3031, error –2.0 ppm.
[6]
Supporting Information (see also the footnote on the first page of
this article): Characterizations, crystal data for 1ʛ3, Job plots, and
UV/Vis data.
Acknowledgments
[7]
[8]
a) F. Huang, K. A. Switek, H. W. Gibson, Chem. Commun.
2005, 3655–3657; b) H. W. Gibson, H. Wang, C. Slebodnick, J.
Merola, W. S. Kassel, A. L. Rheingold, J. Org. Chem. 2007, 72,
3381–3393; c) A. M.-P. Pederson, E. M. Ward, D. V. Schoon-
over, C. Slebodnick, H. W. Gibson, J. Org. Chem. 2008, 73,
9094–9101; d) F. Huang, C. Slebodnick, K. A. Switek, H. W.
Gibson, Chem. Commun. 2006, 1929–1931; e) F. Huang, C. Sle-
bodnick, K. A. Switek, H. W. Gibson, Tetrahedron 2007, 63,
2829–2839.
This work was supported by the National Natural Science Founda-
tion of China (20774086, 20834004, J0830413) and the Fundamen-
tal Research Funds for the Central Universities (2010QNA3008).
[1] a) T.-C. Lin, C.-C. Lai, S.-H. Chiu, Org. Lett. 2009, 11, 613–
616; b) H. Zhang, Q. Wang, M. Liu, X. Ma, H. Tian, Org.
Lett. 2009, 11, 3234–3237; c) J. Cao, H.-Y. Lu, X.-J. You, Q.-
Y. Zheng, C.-F. Chen, Org. Lett. 2009, 11, 4446–4449; d) L.
Du, S. Liao, H. A. Khatib, J. F. Stoddart, J. I. Zink, J. Am.
Chem. Soc. 2009, 131, 15136–15142; e) W.-Y. Wong, K. C.-F.
Leung, J. F. Stoddart, Org. Biomol. Chem. 2010, 8, 2332–2343.
a) S. Li, M. Liu, J. Zhang, B. Zheng, C. Zhang, X. Wen, N.
Li, F. Huang, Org. Biomol. Chem. 2008, 6, 2103–2107; b) S. Li,
M. Liu, J. Zhang, B. Zheng, X. Wen, N. Li, F. Huang, Eur. J.
6808
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6804–6809

Dual-Response Binding in a Bis(1,2,3-phenylene) Cryptand
Org. Chem. 2008, 6128–6133; c) S. Li, M. Liu, B. Zheng, K.
Zhu, F. Wang, N. Li, F. Huang, Org. Lett. 2009, 11, 3350–3353.
[9] a) M. Liu, S. Li, M. Zhang, Q. Zhou, F. Wang, M. Hu, F. R.
Fronczek, N. Li, F. Huang, Org. Biomol. Chem. 2009, 7, 1288–
1291; b) M. Liu, S. Li, M. Hu, F. Wang, F. Huang, Org. Lett.
2010, 12, 760–763.
[15] The chemical shift changes of the protons on the host or guest
after complexation could not be fully recovered. Three possible
reasons are: i. the solution was diluted, ii. the ionic strength of
the solution increased, and iii. different counterions are intro-
duced, influencing ion pairing. These factors could change the
chemical shifts and/or decrease the complexation percentage.
A proton NMR study indicated that the complexation between
the cryptand 1 and Et3NH+·CF3COO– is very weak in CDCl3/
CD3CN, 1:1 at 295 K, so it is appropriate to use triethylamine
as the base here.
[10] L. M. Klivansky, G. Koshkakaryan, D. Cao, Y. Liu, Angew.
Chem. Int. Ed. 2009, 48, 4185–4189.
[11] Z. Xu, X. Huang, J. Liang, S. Zhang, S. Zhou, M. Chen, M.
Tang, L. Jiang, Eur. J. Org. Chem. 2010, 1904–1911.
[12] Selected examples for binding of crown ether derivatives to
paraquat and diquat: a) Q.-S. Zong, C.-F. Chen, Org. Lett.
2006, 8, 211–214; b) T. Han, Q.-S. Zong, C.-F. Chen, J. Org.
Chem. 2007, 72, 3108–3111.
[13] P. Job, Ann. Chim. 1928, 9, 113–203.
[14] Another example of taco complex formation:. Y. Yang, H.-Y.
Hu, C.-F. Chen, Tetrahedron Lett. 2007, 48, 3505–3509.
[16] H. W. Gibson, D. S. Nagvekar, Can. J. Chem. 1997, 75, 1375–
1384.
[17] J. S. Bradshaw, P. Huszthy, C. W. McDaniel, C. Y. Zhu, N. K.
Dalley, R. M. Izatt, S. Lifson, J. Org. Chem. 1990, 55, 3129–
3137.
Received: July 21, 2010
Published Online: October 27, 2010
Eur. J. Org. Chem. 2010, 6804–6809
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6809