Synthesis, structure and inclusion properties of cone-tris{[(5′- methyl-2,2′-bipyridyl)-5-yl]oxycarbonylmethoxy}hexahomotrioxacalix[3]arene

Article abstract of DOI:10.1007/s10847-011-9936-3

Hexahomotrioxacalix[3]arene having [(5′-methyl-2,2′-bipyridyl)- 5-yl]oxycarbonylmethoxy group with cone conformation was prepared, which shows strong Ag⁺ affinity and acts as a ditopic receptor for Ag⁺ and nBuNH₃ ⁺

Full text of DOI:10.1007/s10847-011-9936-3

J Incl Phenom Macrocycl Chem (2011) 71:231–237
DOI 10.1007/s10847-011-9936-3
ORIGINAL ARTICLE
Synthesis, structure and inclusion properties
of cone-tris{[(50-methyl-2,20-bipyridyl)-5-yl]
oxycarbonylmethoxy}hexahomotrioxacalix[3]arene
•
•
•
Xin-Long Ni Masashi Takimoto Zeng Xi
Takehiko Yamato
Received: 22 December 2010 / Accepted: 15 February 2011 / Published online: 17 March 2011
Ó Springer Science+Business Media B.V. 2011
Abstract Hexahomotrioxacalix[3]arene having [(50-methyl-
2,20-bipyridyl)-5-yl]oxycarbonylmethoxy group with cone
conformation was prepared, which shows strong Ag? affinity
and acts as a ditopic receptor for Ag? and nBuNH3?. A con-
formational change of 2,20-bipyridyl moiety from the original
outward orientation of the ring nitrogen to the inside orientation
toward the thiacalixarene cavity was observed in the process of
Ag? complexation.
detail on the influence of O-substituents on the conforma-
tional isomerism of hexahomotrioxacalix[3]arenes 1 [15–
18]. They have established that interconversion between
conformers, which occurs by oxygen-through-the-annulus
rotation, can be sterically allowed for methyl, ethyl, and
propyl groups whereas it is inhibited for the butyl group
[18]. In their studies on the conformer distribution of
hexahomotrioxacalix[3]arene the partial-cone is sterically
less crowded than the cone and therefore formed predomi-
nantly regardless of the choice of the O-alkylation condi-
tions. On the other hand, the cone results as the single
isomer, when a metal ion template, which strongly interacts
with phenolic oxygens, such as ethoxycarbonylmethyl or
N,N-diethylaminocarbonylmethyl group, is present in the
reaction system [15, 18]. However, the selective introduc-
tion of alkoxycarbonylmethyl group on the phenolic groups
has not yet been accomplished in spite of affording a con-
venient starting material for the O-functionalized hexa-
homotrioxacalix[3]arenes.
Keywords Hexahomotrioxacalix[3]arene ꢀ 2,20-Bipyridyl
group ꢀ Ionophore ꢀ Metal complexation ꢀ Ditopic receptor
Introduction
Calixarene and related macrocycles have received consid-
erable attention for their host–guest chemistry as ionophoric
receptors [1–4] and potential enzyme mimics in biology [5–
8]. Chemical modification of calixarene represents an
effective and versatile way of producing receptors with
highly selective cation binding properties [9–12]. Even
minor changes in the regioselective functionalization [13]
or conformation [14] of the chemical modified calixarene
can be associated with drastic changes in the complexation
properties. On the other hand, Shinkai et al. reported in
On the other hand, Nabeshima et al. reported a novel
calix[4]arene derivative bearing two 2,20-bipyridine moie-
ties and two ester groups at the lower rim in cone con-
formation to construct sophisticated molecular devices and
systems [19]. Bipyridyl containing calixarenes have been
extensively used to complex various metal ions [20–27].
Di- or polytopic receptors are those constructed with two or
more binding subunits within the same macrocyclic struc-
ture [28–30]. It is well known that these kinds of systems
are suitable candidates for the allosteric regulation [20–22]
of host–guest interactions with metal cations which play a
major role in biological systems. In this paper we report on
the synthesis of cone-tris{[(50-methyl-2,20-bipyridyl)-5-yl]-
oxycarbonylmethoxy}hexahomotrioxacalix[3]arene from
condensation of cone-hexahomotrioxacalix[3]arene triace-
tic acid with 5-hydroxymethyl-50-methyl-2,20-bipyridine.
X.-L. Ni ꢀ M. Takimoto ꢀ T. Yamato (&)
Department of Applied Chemistry, Faculty of Science and
Engineering, Saga University, Honjo-machi 1, Saga 840-8502,
Japan
e-mail: yamatot@cc.saga-u.ac.jp
Z. Xi
Key Laboratory of Macrocyclic and Supramolecular Chemistry
of Guizhou Province, Guizhou University, Guiyang 550025,
People’s Republic of China
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1
Conformational studies of cone-tris{[(50-methyl-2,20-bip-
yridyl)-5-yl]oxycarbonyl methoxy}hexahomotrioxacalix[3]
arene in solution and its inclusion properties are also
described.
its H NMR spectrum (CDCl3). In the calix[4]arenes, the
Dd values of the ArCH2Ar protons have been correlated to
the orientation of adjacent aromatic rings, i.e. Dd [ 1 ppm
with cone conformation or syn orientation, Dd of about 0.5
with flattened cone or out orientation, Dd of 0 ppm with
1,3-alternate or anti orientation [33]. The same findings
were observed in hexahomotrioxacalix[3]arenes [15].
Thus, we can deduce that cone-8 prefers a flattened cone
conformation.
Results and discussion
5-Hydroxymethyl-50-methyl-2,20-bipyridine 5 was prepared
by 3 steps from 5,50-dimethyl-2,20-bipyridine 2 as shown in
Scheme 1. Thus, the reaction of 2 with N-bromosuccinimide
in the presence of 2,2’-azobis(2,4-dimethylpentanenitrile
(V65) to afford 3 in 58% yield, from which compound 5 was
obtained by the reaction with silver acetate, followed by
hydrolysis of acetate 4.
Interestingly, the hetero aromatic protons of the bipyri-
dine rings of cone-8 are exposed to the ring current
shielding effect [34–36] operating in the opposing bipyri-
dine ring among the dibenzyl ether linkage, and resonate at
higher fields with respect to those of the reference com-
pound 10. The magnitude of this shielding, computed as the
difference between pertinent 2,20-bipyridine protons of
cone-8 and reference compound 10, increases significantly
for the H4, H6 and H3’ protons. The remarkable shielding
effect experienced by the H4 (-0.14 ppm), H6 (-0.12 ppm)
and H3’ (-0.10 ppm) protons of the 2,20-bipyridine suggest
that these protons are located much closer to the neigh-
boring bipyridine ring than the H3 (?0.11 ppm) protons and
are thus shifted stronger upfield. Thus, one nitrogen atom
(N1) in the 2,20-bipyridine ring might be orientated out-
wards with respect to the hexahomotrioxacalix[3]arene
cavity due to the electron repulsion between nitrogens at the
neighboring positions. In contrary, the other nitrogen (N01)
oriented inwards due to the 2,20-bipyridyl linkage
(Scheme 2 and 3).
cone-Hexahomotrioxacalix[3]arene tricarboxylic acid
cone-7 was prepared by hydrolysis of cone-[(N,N-diethyla-
minocarbonyl)methoxy]hexahomotrioxacalix[3]arene cone-
6 with KOH aq. in a mixture of dioxane and water, which was
prepared by O-alkylation of 1 with N,N-diethylchloroacetoa-
mide in the presence of NaH according to the reported pro-
cedures [18, 31]. cone-Hexahomotrioxacalix[3]arene triester
cone-8 was prepared by condensation reaction of cone-7 with
5-hydroxymethyl-50-methyl-2,20-bipyridine (5) in the pres-
ence of DCC (N,N-dicyclohexylcarbodiimide) and DMAP
(4-dimethylaminopyridine) at room temperature for 35 h in
CH2Cl2.
From the singlet peak of calix benzene protons for cone-
8, the conformation was proven to have remained in the
desired cone-conformation. In order to investigate the
conformation of cone-8 in detail, a reference compound 10
was synthesized from 4-tert-butyl-2,6-dimethylphenoxy-
acetic acid 9 [32] following the similar method in the
preparation of cone-8.
As a concave ionophore, that is, cavity-shaped mole-
cules with an inwardly-directed functionality embedded in
the concave position, compound cone-8 was enabled to
Conformation assignment for the new hexahomotriox-
acalix[3]arene triester cone-8 is firmly established by the
presence of AB quartets for the bridging methylene protons
with a Dd separation between Hax and Heq of 0.39 ppm in
N
C
O
7
O
CH2
O
23
N,N-diethylchloro-
acetoamide/ NaH
27
OH
25
OH
CH2
CH2
O
O
in THF,
reflux for 17 h
O
OH
26
(85%)
N
N
3
NBS
Me
cone-6
Me
Me
CH2Br
15
V
65 in CH2Cl2
N
N
R
reflux for 24 h
(58%)
1
CH2
O
3
2
OH
C
O
C O
N
AgOAc
RCH2OH (5)
CH2
O
CH2
O
Me
CH2OAc
DCC/DMAP
in CH2Cl2
Dioxane/
KOH aq.
in AcOH
at 85–90°C
for 12 h
N
CH2
CH2
CH2
CH2
4
O
O
reflux for 24 h
(85%)
room temp.
for 35 h
(55%)
(42%)
3
3
N
KOH/ EtOH
cone-7
Me
CH2OH
N
at 50°C
for 15 min
cone-8; R=
Me
N
N
5
Scheme 2 Synthesis of cone-hexahomotrioxacalix[3]arene triester
cone-8
Scheme 1 Synthesis of 5-hydroxymethyl-50-methyl-2,20-bipyridine 5
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J Incl Phenom Macrocycl Chem (2011) 71:231–237
233
6
3'
4'
6'
5.85; Dd = -2.45 ppm). These phenomena were also
proven the n-butyl ammonium ion was encapsulated into
the cavity formed by the benzene rings and changed the
conformaton of compound cone-8.
N
Me
CH2
N
OH
C
4
3
O
C
O
O
CH2
O
CH2
O
RCH2OH (5)
As mentioned previously, Dd between Hax and Heq of
the ArCH2Ar methylene protons in calix[4]arene serves as
a measure of the ‘flattening’. Dd increases from d 0.41 ppm
DCC/DMAP
in CH2Cl2
Me
Me
Me
Me
room temp.
for 35 h
?
to d 0.86 ppm in cone-8 upon the binding of n-BuNH3
upon the binding of n-BuNH3?, respectively. These find-
ings imply that cone-8 stands up when the guest is included
9
10
?
Scheme 3 Synthesis of the reference compound 10
because n-BuNH3 enters into the p-cavity formed by
three aromatic rings.
bind with metal cations and primary ammonium ions. The
complexation mode was elucidated quantitatively by the
NMR titration of nuclear magnetic resonance. Interest-
ingly, depending on the ionic size, complexing behavior
was different in the complex of compound cone-8 with
these cations.
Due to the existence of the three potential metal-binding
sites, namely the bipyridine moieties, two ester moieties
and calix benzene rings, there are several possibilities for
metal complexation for compound cone-8 with guest
molecules. Either 1:1 or 1:2 metal complexation might be
possible attributable to the electrostatic interactions as well
as cation-p interactions. The Job plots of compound cone-8
were carried out in the H2O/CH2Cl2 phases. The percent
extractions reach maximum at 0.5 mol fraction when the
cone-8 and silver cation are changed systematically. This
fact clearly indicates that the Ag? cation forms a 1:1
complex with cone-8. This result suggests the major con-
tribution is from the nitrogen of 2,20-bipyridine ring to Ag?
binding, but not a cation–p-interaction with calix benzene
rings or the oxygen on the bridged linkage.
The C3-symmetrical conformation of compound cone-8
makes it possible to bind with primary ammonium ions [16,
18]. The present ammonium ions binding mode can be also
demonstrated more clearly by using 1H NMR spectroscopy.
There are two modes for cone-8 to bind with n-butyl
ammonium ions, i.e. from the lower rim through substitu-
ents moieties or from the upper rim through the p-cavity
formed by three aromatic rings. After adding an equivalent
of n-BuNH3?Pic- to a solution of cone-8 (5 9 10-3 M) in
CDCl3 at 27 °C, peak signals of compound cone-8
appeared both of complex and of free host, respectively.
With increasing the amount of ammonium ion excessively,
the signals of compound cone-8 decreased and finally only
the complex signals were observed. In comparison with the
free host, in the complex, the protons of calix benzene rings
shifted to lower field (from d 6.91 to 7.32 ppm), while the
chemical shift changes of the 2,20-bipyridyl (Bipy) protons
were negligibly small in the cone-8 complexes n-butyl
ammonium ion. These findings suggest the conformational
change in the 2,20-bipyridyl moiety might be small after
complexation with n-butyl ammonium. Furthermore, the
axial protons in the bridge methylene, which was related to
the conformation of calixarene, were shifted to lower
magnetic field (from d 4.85 to 5.20 ppm), while the
equatorial protons shifted to upper field (from d 4.46 to
4.30 ppm). The methylene protons of ArOCH2 were also
shifted to lower field (from d 4.55 to 4.95 ppm). With
excess of n-BuNH3?Pic-, the free guest molecules and the
encapsulated molecules were clearly observed by the pro-
ton 1H NMR spectroscopy, in which the encapsulated
one was shifted to upfield, CH3 (0.95 to 0.26, Dd =
-0.69 ppm), CH3CH2 (1.45 to 0.30, Dd = -1.05 ppm),
CH3CH2CH2 (1.77 to -0.30, Dd = -2.07 ppm) and CH2N
(3.00 to 0.30, Dd = -2.70 ppm). The chemical shift of NH
in n-BuNH3?Pic- was shifted to upper field (d 8.30 to
In order to explore the binding mode of three lower-rim
1
side chains having pyridyl groups, we examined the H
NMR chemical shift differences between those before and
after the addition of an equiv. KSO3CF3 or AgSO3CF3 in
CDCl3–CD3CN, and composition of the ion–ionophore
complex. The addition of an equiv. of KSO3CF3 to cone-8
causes negligible chemical shift. On the other hand, titra-
tion with an equivalent of AgSO3CF3 causes a low field
shift for the 2,20-bipyridyl (Bipy) protons shifted with d
0
?0.24, ?0.34 ppm for H4, H4 protons, and shifted to upper
0
field with -0.17, -0.10, -0.13 ppm for H3, H3 , H6 pro-
tons, respectively (Fig. 1c). These observations might be
attributed to the conformational change of the bipyridyl
moieties in cone-8 upon complexation. Thus, the cone-8
complexes Ag? through the both metal-nitrogen electro-
static interactions of bipyridyl group by tetrahedral Ag?/
heterocycle complex. Interestingly, contrary to the obser-
vation of chemical shift changes of the bipyridyl protons,
the chemical shift changes of the methylene protons of
OCH2Bipy moiety and ArCH2O were negligibly small in
the cone-8 complexes Ag?. These findings suggest the
conformational changes in calix benzene and ester moieties
might be small after complexation with Ag?.
Compound cone-8 was treated with silver cation and n-
1
butyl ammonium ion in a H NMR titration to investigate
the behavior as a ditopicreceptors. At first, with adding an
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J Incl Phenom Macrocycl Chem (2011) 71:231–237
Me
Me
N
N
N
N
N
N
Ag+
N
N
N
N
N
N
Ag+
O
O
O
O
O
O
O
O
H
O
O
O
O
O
H
H
O
O
O
O
O
O
N+
Pic-
O
+
n-Bu
NH3
O
O
O
O
cone-8
Ditopic receptor
CH3CH2CH2CH2–
Fig. 2 Plausible binding mode of cone-8 with Ag? and n-BuNH3Pic
protons which shift to upper field due to the tetrahedral
interaction of N—Ag?. Furthermore, the C3-symmetrical
conformation of cone-8 is still retained after complexation
with both n-butyl ammonium ion and silver ion.
Fig. 1 Partial 1H NMR spectra of cone-8 (CDCl3:CD3CN, 2 9 10-3
M) a) Free cone-8,b) cone-8 , n-BuNH3?Pic- (1:1); c) Ag?.cone-8
(1:1); d) [Ag?.cone-8 , n-BuNH3?Pic-]
equivalent of silver cation, the chemical shift of protons
peaks was changed as described above. The further
investigation was complex Ag?.cone-8 in the presence of
n-butyl ammonium ion. The results were shown in Fig. 1d.
The induced chemical shift to upper field of n-butyl
ammonium protons strongly suggested the complexation of
Ag?.cone-8 with n-butyl ammonium ion. Furthermore,
the conformation of the host was changed too. The
chemical shift difference between the axial proton and
equatorial proton in bridge methylene was increased upper
to d 0.92 ppm under the presence of both n-butyl ammo-
nium ion and silver cation, which was mostly contributed
by the complexation with n-butyl ammonium ion. Fur-
thermore, the chemical shift of protons on pyridine rings
showed small changes (0.04–0.10 ppm) proving that the
complex with silver cation remained intact after the
Ag?.cone-8 complex was treated with the n-butyl
ammonium ion. Thus, compound cone-8 can complex with
n-butyl ammonium ions and silver cation at the same time
to form the heteroditopic complexation. Compound cone-8
shows association constant for n-butylammonium ion
(Ka = 18.25 9 103 M-1 in CDCl3–CD3CN 10:1). The
complex ability decreases in the presence of Ag? ion
(Ka = 7.55 9 103 M-1 in CDCl3–CD3CN 10:1) due to
strong electrostatic repulsion between n-butylammonium
ion and silver ion included in the cavity of cone-8.
Conclusions
For the first time, the relationship between properties of
soft-hard ionophore hosts and alkyl ammonium ion was
taken into account in C3-symmetric conformation. cone-8
can bind n-butyl ammonium ions through the p-cavity
formed by three aryl rings, which can provide functional
moieties in biologic systems with good affinity and high
selectivity. As C3-symmetrical bipyridyl-substituted calix-
arene, ionophore cone-8 can also bind Ag? ion and the
complexation mode was elucidated clearly in this paper.
Thus, ionophore cone-8 acts as a heteroditopic receptor
which can complex with Ag? and n-BuNH3 at the same
?
time. The nitrogen atom in the bipyridine rings turned from
outward from the cavity to inside the cavity to interact with
Ag?. After complexation of cone-8 with Ag?, the original
C3-symmetry has been remained for cone-8. To the best of
our knowledge the present result is the first example of
heterogeneous dinuclear complex in the hexahomotriox-
acalix[3]arene family. These results give some insight into
the molecular design of new synthetic receptors for use in
anion controlled of biomimetic systems.
Experimental
As shown in Fig. 2, the nitrogen atom (N1) in the
bipyridine ring points away from the calix cavity in the free
cone-8 because of the electron repulsion between nitro-
gens. After complexation, the nitrogen turns inwards
toward0s the cavity to complexwith Ag? and thus af0fects
H4, H4 protons which shift to lower field and H3, H3 , H6
All mps (Yanagimoto MP-S1) are uncorrected. NMR
spectra were determined at 300 MHz with a Nippon Denshi
JEOL FT-300 NMR spectrometer with SiMe4 as an internal
reference: J-values are given in Hz. IR spectra were mea-
sured for samples as KBr pellets or a liquid film on NaCl
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J Incl Phenom Macrocycl Chem (2011) 71:231–237
235
0
0
plates in a Nipon Denshi JIR-AQ2OM spectrophotometer.
UV spectra were measured by Shimadzu 240 spectropho-
tometer. Mass spectra were obtained on a Nippon Denshi
JMS-01SA-2 spectrometer at 75 eV using a direct-inlet
system through GLC. Elemental analysis: Yanaco MT-5.
Materials. Hexahomotrioxacalix[3]arene 1 was prepared
according to the literature [15, 16]. cone-Hexahomotriox-
acalix[3]arene triacetic acid cone-7 was prepared according
to the literature [18, 31].
J = 5.7 Hz, Bipy–H4 ), 8.28(1H, d, J 7.8 Hz, Bipy–H3 ),
0
8.36 (1H, d, J 8.4 Hz, Bipy–H3), 8.50 (1H, s, Bipy–H6 )
and 8.65 (1H, s, Bipy–H6). MS m/z 242 (M?). Anal. Calcd
for C14H14N2O2 (242.28): C, 69.41; H, 5.82; N, 11.56.
Found: C, 69.61; H, 5.72; N, 11.48%.
Synthesis of (50-methyl-2,20-bipyridinyl-5-yl)methanol (5)
A solution of 50-methyl-2,20-bipyridinyl-5-yl-methyl ester
(4) (140 mg, 0.58 mmol) aq.KOH (335 mg, 5.97 mmol in
2 mL of H2O) in ethanol (10 mL) was heated and stirred
for 25 min at 50 °C. The reaction mixture then cooled to
room temperature and solvent was evaporated. The residue
extracted with CH2Cl2 (2 9 50 mL) and washed with
water (2 9 50 mL). The organic phase dried over with
MgSO4, and condensed under reduced pressure. The resi-
due was recrystallization from hexane to give pure product
(50-methyl-2,20-bipyridinyl-5-yl)methanol 5 (97 mg, 83%)
as colourless prisms, Mp 110–111 °C. 1H NMR d (CDCl3)
2.40 (3H, s, Bipy–CH3), 4.79 (2H, d, J = 5.4 Hz, Bipy–
Synthesis
Synthesis of 5-monobromomethyl-50-methyl-2,20-
bipyridine (3)
A solution of 5,50-dimethyl-2,20-bipyridine 2 (500 mg, 2.71
mmol), N-bromosuccinimide (NBS) (531 mg, 2.98 mmol)
and 2,20-azobis(2,4-dimethyl-pentanenitrile) (V65) (300 mg,
1.20 mmol) in CH2Cl2 (100 mL) refluxed 12 h under argon
protect. Thereactionmixture was cooled toroom temperature
and then solvent was evaporated. The residue dissolved in hot
hexaneandthesolid part offout. The filtratesolution keep 4 h
at room temperature, dibromomethyl derivatives was pre-
cipitated and separated by filtration. The filtrate part again
reduced one-third volume and put 12 h at room temperature
to afford white solid, which was recrystallization from eth-
ylacetate/hexane(1:1) to give pure product 3 (410 mg, 58%)
as a white powder, Mp 85–87 °C. 1H NMR d (CDCl3) 2.39
(3H, s, bipy–CH3), 4.53 (2H, s, –CH2Br), 7.62 (1H, d,
0
CH2–), 7.82 (1H, d, J 8.4 Hz, Bipy–H4 ), 7.82 (1H, d,
0
J 6.0 Hz, Bipy–H4), 8.27 (1H, d, J 7.8 Hz, Bipy–H3 ), 8.36
0
(1H, d, J = 8.1 Hz, Bipy–H3), 8.50 (1H, s, Bipy–H6 ) and
8.65 (1H, s, Bipy–H6). MS m/z 200 (M?). Anal. Calcd for
C12H12N2O (200.24): C, 71.98; H, 6.04; N, 13.99. Found:
C, 71.73; H, 6.12; N, 13.68%.
Preparation of cone-hexahomotrioxacalix[3]arene
triacetic acid (cone-7)
0
J 7.8 Hz, bipy–H4 ), 7.83(1H, d, J 6.0 Hz, bipy–H4), 8.28
0
(1H, d, J 7 .8 Hz, bipy–H3 ), 8.35 (1H, d, J 8.4 Hz, Bipy–H3),
8.49 (1H, s, Bipy–H6 ) and 8.65 (1H, s, Bipy–H6). 13C NMR
A mixture of cone-6 (1.0 g, 1.14 mmol) in dioxane
(35 ml), was added 1 N KOH aqueous solution (40 mL).
After the mixture was refluxed for 24 h, it was condensed
under reduced pressure, and then acidified by hydrochloric
acid to pH 1–2. The dispersion was extracted with ethyl
acetate (2 9 20 mL). The combined extracts were washed
with water (2 9 20 mL), saturated brine (20 mL), dried
(MgSO4) and condensed under reduce pressure. The resi-
due was washed with small amount of diethyl ether to give
the crude cone-7 as a colorless solid. Recrystallization from
methanol to give cone-7 (730 mg, 85%) as colorless
powder; Mp 227–229 °C (lit. [31] Mp 227–229 °C).
0
(75 MHz) d 156.08, 150.05, 138.32, 134.59, 121.87 and
30.22. MS m/z 264 (M?). Anal. Calcd for C12H11BrN2
(263.14): C, 54.77; H, 4.21; N, 10.65. Found: C, 54.97; H,
4.42; N, 10.88%.
Synthesis of 50-methyl-2,20-bipyridinyl-5-yl-methyl ester (4)
A solution of 5-bromomethyl-50-methyl-2,20-bipyridinyl
(3) (300 mg, 1.14 mmol) and silver acetate (951 mg,
5.7 mmol) in acetic acid(30 mL) was heated at 85–90 °C
for 20 h. The reaction mixture was allowed to cool to room
temperature and acetic acid was evaporated. The residue
extracted with CH2Cl2 (2 9 50 mL), and washed with 10%
Na2CO3 (20 mL) and water (2 9 30 mL), the organic layer
was separated and dried over with MgSO4, then condensed
under reduced pressure. The residue was recrystallization
from hexane to give pure product 50-methyl-2,20-bipyridi-
nyl-5-yl-methyl ester 4 (116 mg, 42%) as colourless
Synthesis of cone-7,15,23-tri-tert-butyl-25,26,27-tris
{[(50-methyl-2,20- bipyridinyl)-5-yl]methoxy}-
2,4,10,12,18,20-hexahomo-3,11,19-trioxacalix[3]arene
(cone-8)
(50-Methyl-2,20-bipyridinyl-5-yl)methanol 5 (85 mg, 0.42
mmol) and 4-dimethylaminopyridine (DMAP) (52 mg,
0.42 mmol) were added to a solution of cone-7 (50 mg,
0.066 mmol) in CH2Cl2 (6 mL). The mixture was stirred at
0 °C while a solution of N,N-dicyclohexylcarbodiimide
1
prisms, Mp 62–63 °C. H NMR d (CDCl3) 2.12 (3H, s,
–COCH3), 2.40 (3H, s, Bipy–CH3), 5.17 (2H, s, Bipy–
0
CH2–), 7.62 (1H, d, J 6.3 Hz, Bipy–H4 ), 7.80 (1H, d,
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J Incl Phenom Macrocycl Chem (2011) 71:231–237
1H NMR complexation experiment
(DCC) (96 mg, 0.46 mmol) in CH2Cl2 (6 mL) was added
drop wise. The solution was stirred 1 h at 0 °C and 35 h at
room temperature. After completion, filtering of the insoluble
solid, CH2Cl2 was removed under reduce pressure. The resi-
due was dissolved in AcOEt and filtrated. The filtrate was
washed sequentially with 10% citric acid (2 9 25 mL), water
(2 9 25 mL), 5% sodium bicarbonate (20 25 mL), and brine
(30 mL). The organic layer was dried (MgSO4), and con-
centrated. The residue was washed several times with hexane,
and recrystalization from methanol to give the product cone-8
(47 mg, 55%) as colourless prisms, Mp 95–97 °C. IR mmax
(KBr)/cm-1 3431, 2955, 2863, 1760, 1610, 1557, 1470, 1362,
1188, 1068, 883, 830, 741 and 651 cm-1. 1H NMR d (CDCl3)
1.07 (27H, s, tBu), 2.35 (9H, s, Bipy–CH3), 4.46 (6H, d,
J 12.9 Hz, ArCH2O–), 4.55 (6H, s, ArOCH2–), 4.85 (6H, d,
J12.9 Hz, ArCH2O–), 5.21(6H,s, Bipy–CH2O–), 6.91(6H, s,
A CDCl3 solution (1.53 9 10-3 M, 400 lL) of cone-8 in
the NMR tube, was added a CD3CN solution (1.53 9
10-2 M, 40 lL) of an equivalent of n-BuNH3?Pic-. The
spectrum was recorded after addition and the temperature
of NMR tube kept constant at 27 °C. The association
constants values were calculated by the integral intensity of
CH2 protons [ArOCH2Bipy] in the complex and free host
molecules according to the literature [37].
Acknowledgements We would like to thank the OTEC at Saga
University for financial support and the International Collaborative
Project Fund of Guizhou province at Guizhou University.
0
Ar–H), 7.54 (3H, d, J 6.0 Hz, Bipy–H4 ), 7.76 (3H, d,
0
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