Synthesis, structure and inclusion properties of distal-bis{[(5'-methyl-2, 2,-bipyridyl)-5-yl]methoxy}tetrathiacalix[4]arene with 1,2-alternate conformation

Article abstract of DOI:10.3184/030823409X396436

distal-Tetrathiacalix[4]arene having [(5'-methyl-2,2'-bipyridyl)-5-yl] methoxy group with 1,3-alternate conformation was prepared, which shows strong Ag⁺ affinity and the high Ag⁺ selectivity. The conformational change of 2,2'-bipyri

Full text of DOI:10.3184/030823409X396436

104 RESEARCH PAPER
FEBRUARY, 104–108
JOURNAL OF CHEMICAL RESEARCH 2009
Synthesis, structure and inclusion properties of distal-bis{[(5'-methyl-
2,2'-bipyridyl)-5-yl]methoxy}tetrathiacalix[4]arene with 1,3-alternate
conformation
Tomoe Shimizua, Shofiur Rahmana, Zeng Xib and Takehiko Yamatoa*
aDepartment of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga-shi,
Saga 840-8502, Japan
bKey Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang, Guizhou,
550025, P.R. China
distal-Tetrathiacalix[4]arene having [(5'-methyl-2,2'-bipyridyl)-5-yl]methoxy group with 1,3-alternate conformation
was prepared, which shows strong Ag+ affinity and the high Ag+ selectivity. The conformational change of 2,2'-
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.
Keywords: thiacalix[4]arene, O-alkylation, 2,2'-bipyridyl group, conformation, ionophores, metal complexation
The introduction of larger alkyl groups on the phenolic
oxygens of calix[4]arenes led to a situation where the OR
groups within a cyclophane ring cannot pass each other by
oxygen-through-the-annulus rotation.1–4 There exist four
possible conformational isomers in calix[4]arenes; i.e. cone,
partial-cone, 1,2-alternate and 1,3-alternate.1–4 Similarly,
four conformational isomers are possible in the case of
tetrathiacalix[4]arene.5–7 The inhibition of interconversion
between conformers derived from tetrathiacalix[4]arene by
O-substitution differs from that of the calix[4]arenes. On the
other hand, the regioselective O-alkylation of hydroxy groups
in calixarenes is important for many purposes, in particular
for the construction of multiple binding receptors or larger
molecules starting from several calixarene building units.8,9
In fact, we previously reported10 that 5,11,17,23-tetra-
tert-butyl-25,26,27,28-tetrahydroxytetrathiacalix[4]arene
when treated with 2-(chloromethyl)pyridine in the presence
of Na2CO3ꢀ XQGHUꢀ 7+)ꢀ UHÀX[ꢀ \LHOGHGꢀ QRQHꢀ RIꢀ WKHꢀ SXUHꢀ
regioselective isomers such as 1,2- or 1,3-di-O-substitution.
Only a trace amount of a mixture of partial (2-pyridyl)
methylation products were obtained along with the recovery
of the starting compound. Recently, we have reported that
regioselective synthesis of distal-bis[(2-pyridylmethyl)oxy]
thiacalix[4]arenes is accomplished by a protection-deprotection
method using benzyl groups as a protecting group.11
procedure.11 O-Alkylation of distal-2 with 5-bromomethyl-
5'-methyl-2,2'-bipyridine 3 in the presence of Cs2CO3 as base
LQꢀDFHWRQHꢀXQGHUꢀUHÀX[ꢀIRUꢀꢁꢂꢀKꢀ\LHOGHGꢀWKHꢀGHVLUHGꢀSURGXFW
1,3-alternate-4 in 68% yield. Similarly, O-alkylation of
distal-2 with 5-bromomethyl-5'-methyl-2,2'-bipyridine 3 in
the presence of NaH or K2CO3 afforded 1,3-alternate-4 in 55
and 59% yields, respectively. However, no formation of the
other possible conformational isomers such as partial-cone
or cone isomers was observed. In the case of Na2CO3 only
the recovery of starting compounds resulted in spite of the
conditions of large excess of Na2CO3 and 5-bromomethyl-5'-
methyl-2,2'-bipyridine 3.
The 1H NMR spectrum of 1,3-alternate-4 shows two singlet
peaks for tert-butyl protons, in which both tert-butyl protons
ZHUHꢀREVHUYHGꢀWRꢀKLJKHUꢀ¿HOGꢀDWꢀG 0.78 and 0.86 ppm due to
the ring current effect arising from the two benzyl benzene
rings and the two 2,2'-bipyridine rings introduced.
Interestingly, the hetero aromatic protons of the bipyridine
rings of 1,3-alternate-4 are exposed to the ring current shielding
effect26–28 operating in the opposing bipyridine ring among the
GLDU\OꢀWKLDHWKHUꢀOLQNDJHꢃꢀDQGꢀUHVRQDWHꢀDWꢀKLJKHUꢀ¿HOGVꢀZLWKꢀUHVSHFWꢀ
to those of the reference compound 6, which was prepared by
On the other hand, Nabeshima et al.12 reported a novel
calix[4]arene derivative bearing two 2,2'-bipyridine moieties
and two ester groups at the lower rim in cone conformation
to construct sophisticated molecular devices and systems.
Bipyridyl containing calixarenes have been extensively used
to complex various metal ions.13–22 Di- or polytopic receptors
are those constructed with two or more binding subunits within
the same macrocyclic structure.23–25 It is well known that
these kinds of systems are suitable candidates for the allosteric
regulation13–16 of host-guest interactions with metal cations
which play a major role in biological systems. We now report
on the synthesis of distal-bis{[(5'-methyl-2,2'-bipyridyl)-5-yl]
methoxy}tetrathiacalix[4]arene from O-alkylation of distal-
di-O-alkoxythiacalix[4]arene with 5-bromomethyl-5'-methyl-
2,2'-bipyridine. Conformational studies of distal-bis{[(5'-
methyl-2,2'-bipyridyl)-5-yl]methoxy}tetrathiacalix[4]arene in
solution and its inclusion properties are also described.
S
S
S
S
OH
S
O
OH
OH
OH HO
OH
O
BzlBr, Na2CO3
S
S
acetone
S
reflux for 17 h.
(98%)
distal-2
1
N
Me
N
O
Br
O
3
S
S
Cs2CO3
acetone
S
S
O
O
reflux for 17 h
(68%)
6
5
3
4
N
N
2
N
6'
2'
3'
Results and discussion
N
4'
1,3-distal-Bis(benzyloxy)tetrathiacalix[4]arene, distal-2, was
prepared by O-alkylation of thiacalix[4]arene 1 with benzyl
bromide in the presence of Na2CO3 according to the reported
5'
1,3-alternate-4
* Correspondent. E-mail: yamatot@cc.saga-u.ac.jp
Scheme 1

JOURNAL OF CHEMICAL RESEARCH 2009 105
3'
6
4'
N
N
Me
CH2
O
Me
N
6'
4
3
OH
Br
N
Me
Me
Me
Me
3
NaH
THF-DMF
reflux for 17 h
(63%)
5
6
Scheme 2
O-alkylation of 4-tert-butyl-2,6-dimethylphenol 529 with 5-
bromomethyl-5'-methyl-2,2'-bipyridine 3 in the presence of NaH.
The magnitude of this shielding, computed as the difference
between pertinent 2,2'-bipyridine protons of 1,3-alternate-
4 and reference compound 6ꢃꢀLQFUHDVHVꢀVLJQL¿FDQWO\ꢀIRUꢀWKHꢀ
H4, H6 and H6' protons. The remarkable shielding effect
experienced by the H4 (–0.38 ppm) and H6 (–0.26 ppm)
protons of the 2,2'-bipyridine suggest that these protons are
located much closer to the opposing bipyridine ring than are
the H3 proton and folded into the S-cavity formed by two
WKLDFDOL[ꢀEHQ]HQHꢀULQJVꢀDQGꢀDUHꢀWKXVꢀVKLIWHGꢀVWURQJHUꢀXS¿HOGꢄꢀ
Thus, one nitrogen atom (N1) of the 2,2'-bipyridine ring might
be orientated outwards with respect to the thiacalixarene
cavity due to the electron repulsion between nitrogens at the
distal positions. In contrast, the other nitrogen (N1') is oriented
inwards due to the 2,2'-bipyridyl linkage.
Calixarenecanbeconvertedtoneutralligandsbyintroduction
of ester or amide groups into the OH groups.1 The metal
selectivity is dependent on the ring size and the O-alkylated
VXEVWLWXHQWVꢀSUHVHQWꢄꢀ7KHꢀULQJꢀVL]HꢀDQGꢀWKHꢀULQJꢀÀH[LELOLW\ꢀRIꢀ
thiacalix[4]arene are different from both calix[4]arene and
hexahomotrioxacalix[3]arene.1 Functionalisation of calix[4]
arene by O-alkylation with halomethyl N-heterocyclic
reagents in the presence of the base has been introduced in
order to obtain “universal” ligands for both hard and soft
metal ions, which in principle should exhibit some advantages
over ester and amide structures, because of a high stability
over a wide pH range.30,31 Recently, Pappalardo has reported
the synthesis of calix[4]arenes bearing pendant pyridine
groups at the lower rim as potential ligands for transition
metal cations.32,33 Similar investigation was also carried out
using hexahomotrioxacalix[3]arene and homocalix[3]arene as
the platform.34–37 Therefore, it is interesting to assess the type
of ionophoric cavity provided by the bis{[(5'-methyl-2,2'-
bipyridyl)-5-yl]methoxy} derivative 1,3-alternate-4. Usually,
calixarenes form a 1:1 complex with guest molecules, but
various other types of complexation were observed depending
on the calix ring size and functional groups present. A 1:2
complex of calix[8]arene with ammonium ions was reported
by Shinkai.38-41 The 1,3-alternate conformer of calix[4]arene
derivatives can also form a 1:2 complex with metal cations.42
Due to the existence of the three potential metal-binding
sites, namely the bipyridine moieties, two benzyloxy moieties
and calix benzene rings, there are several possibilities for
metal complexation for compound 1,3-alternate-4 with guest
molecules. Both 1:1 or 1:2 metal complexation might be
possible attributable to the electrostatic interactions as well
as cation–S interactions. The Job plots of compound 1,3-
alternate-4 were carried out in the H2O/CH2Cl2 phases. The
percent extractions reach maximum at 0.5 mole fraction
when the 1,3-alternate-4 and silver cation are changed
systematically. This fact clearly indicates that the Ag+ forms
a 1:1 complex with 1,3-alternate-4. This result suggests the
major contribution is from the nitrogen of 2,2'-bipyridine
ring to Ag+ binding, but not a cation–S-interaction with calix
benzene rings nor the sulfur on the bridged linkage.
Fig. 1 Job plots of the extractions of Ag+ with host 1,3-
alternate-4.
Preliminary studies of the binding ability of 1,3-alternate-
4 are carried out by ion-pair extraction [M+Pic- (M+ = Ag+
or K+)]. The E% value of 98% for 1,3-alternate-4, shows
that 1,3-alternate-4 strongly extract Ag+. In contrast, no
VLJQL¿FDQWꢀ(ꢅꢀLVꢀREVHUYHGꢀIRUꢀ.+ (1.5%) for 1,3-alternate-4.
The association constant Kass for the 1,3-alternate-4ŠAg+ is
K
ass = 3.1 u 103 M-1ꢀFDOFXODWHGꢀE\ꢀQRQꢆOLQHDUꢀ¿WWLQJꢀDQDO\VLVꢀRIꢀ
the observed chemical shift changes of OCH2Bipy protons.43
1H NMR titration experiments in CDCl3–CD3CN and
with KSO3CF3 and AgClO4 are carried out. The addition of
an equiv. of KSO3CF3 to 1,3-alternate-4 causes negligible
chemical shift. On the other hand, titration with an equiv. of
AgClO4ꢀFDXVHVꢀDꢀXS¿HOGꢀVKLIWꢀIRUꢀWKHꢀPHWK\OHQHꢀSURWRQVꢀRIꢀ
OCH2Bipy ('G = –0.20 ppm) while the 2,2'-bipyridyl (Bipy)
SURWRQVꢀVKLIWHGꢀWRꢀORZHUꢀ¿HOGꢀZLWKꢀG + 0.40, + 0.43 ppm for H4,
H4'ꢀSURWRQVꢃꢀDQGꢀVKLIWHGꢀWRꢀXSSHUꢀ¿HOGꢀZLWKꢀ±ꢇꢄꢁꢈꢃꢀ±ꢇꢄꢁꢉꢀSSPꢀ
for H6, H6' protons, respectively (Fig. 2). These observations
might be attributed to the conformational change of the 1,3-
alternate-4 upon complexation. Thus, the 1,3-alternate-4
complexes Ag+ through the both metal-nitrogen electrostatic
interactions of bipyridyl group by tetrahedral Ag+/heterocycle
complex.13–22 Interestingly, contrary to the observation of
GRZQ¿HOGꢀ VKLIWꢀ RIꢀ WKHꢀ PHWK\OHQHꢀ SURWRQVꢀ RIꢀ 2CH2Bipy
('G = –0.20 ppm), the chemical shift changes of the protons
of OCH2Ph moiety were negligibly small in the 1,3-alternate-
4 complexes Ag+ꢄꢀ7KHVHꢀ¿QGLQJVꢀVXJJHVWꢀWKHꢀFRQIRUPDWLRQDOꢀ
change in the opposing OCH2Ph moiety might be small
after complexation with Ag+ different from the reported 1,3-
alternate-thiacalixarene derivatives.11
In order to study the present conformational behaviour
more detail, we have prepared the corresponding N,N-
diethylamide derivative 1,3-alternate-8 by O-alkylation of
distal-2 with N,N-diethylchloroacetamide 7 in the presence
of Cs2CO3 in 68% yield. Similar phenomena were also
observed in the complexation of 1,3-alternate-8 with Ag+.

106 JOURNAL OF CHEMICAL RESEARCH 2009
-0.17
+0.08
-.0.09
-0.26
0.00
-0.01
CH2
CH2
O
+0.18
+0.01
+0.01
O
+0.06
-0.02
S
S
S
S
-0.09
-0.02
-0.25
O
O
+0.06
-0.20
-0.13
2
2
CH2
C
CH2
-0.10
+0.40
-0.02
O
N
N
+0.09
+0.27
+0.02
+0.16
-0.03
N
-0.14
+0.43
1,3-alternate-8
Me
+0.15
1,3-alternate-4
Fig. 2 Chemical shift changes of 1,3-alternate-4 and 1,3-alternate-8 induced in the presence of AgClO4 in CDCl3: CD3CN (10:1);
+ denotes the downfield and – denotes the upfield shift.
O O
O
N
O
O
S
S
O
S
S
Ag+
(7)
ClCH2CONEt2
Cs2CO3
S
S
S
S
S
S
O
O
O
N
O
distal-2
S
S
O
O
acetone
N
reflux for 17 h
(68%)
N
N
Ag+
N
O
C
N
O
C
N
N
N
Me
Me
1,3-alternate-4-Ag+ complex
1,3-alternate-8
1,3-alternate-4
Fig. 3 Complexation mode of 1,3-alternate-4 with Ag+.
Scheme 3
7KHꢀ VPDOOꢀ GRZQꢆ¿HOGꢀ VKLIWVꢀ RIꢀ WKHꢀ PHWK\OHQHꢀ SURWRQVꢀ DQGꢀ
ethyl protons of N,N-diethylamide moieties ('G = + 0.06 ppm
for CH2CONEt2) were observed, which may be attributed to
the smaller conformational change of the amide moieties upon
complexation of 1,3-alternate-8 with Ag+ than that of 1,3-
alternate-4 (Fig. 2). In contrast, the chemical shift changes
of the opposing inverted calix benzene protons and CH2Ph
protons are much larger than those of 1,3-alternate-4. These
¿QGLQJVꢀVXJJHVWꢀWKHꢀFRQIRUPDWLRQDOꢀFKDQJHꢀLQꢀWKHꢀRSSRVLQJꢀ
OCH2Ph moiety after complexation of 1,3-alternate-8 with
Ag+ might be larger than that of 1,3-alternate-4.
As shown in Fig. 3, the nitrogen atom (N1) in the bipyridine
ring points away from the calix cavity in the free 1,3-alternate-
4 because of the electron repulsion between nitrogens. After
complexation, the nitrogen turns inwards towards the cavity
to complex with Ag+ and thus affects H4, H4' protons which
VKLIWꢀWRꢀORZHUꢀ¿HOGꢀDQGꢀ+6, H6' protons which shift to upper
¿HOGꢀGXHꢀWRꢀWKHꢀWHWUDKHGUDOꢀLQWHUDFWLRQꢀRIꢀ1ꢆꢆꢆ$J+. However,
the conformational change in the bipyridyl moieties does
not affect that of the opposing benzyl moieties. Furthermore,
the C2V-symmetrical conformation of 1,3-alternate-4 is still
retained after complexation.
been accomplished by O-alkylation of 25,27-bis(benzyloxy)-
26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-2,8,14,20-
tetrathiacalix[4]arene, distal-2 with 5-bromomethyl-5'-
methyl-2,2'-bipyridine. C2V-Symmetrical bipyridyl-substituted
thicalix[4]arene, 1,3-alternate-4 can bind Ag+ ion and the
complexation mode has been elucidated clearly. The nitrogen
atom in bipyridine ring turned from outward against the cavity
to inside the cavity to interact with Ag+ in 1,3-alternate-4. After
complexation of 1,3-alternate-4 with Ag+, the original C2V-
symmetry has been remained. Further studies on the application
to the synthetic receptors for use in metal controlled biomimetic
systems are now in progress.
Experimental
All melting points are uncorrected. 1H NMR spectra were recorded
at 300 MHz on a Nippon Denshi JEOL FT-300 NMR spectrometer
in deuteriochloroform with Me4Si as an internal reference. IR spectra
were measured as KBr pellets on a Nippon Denshi JIR-AQ2OM
spectrometer. Mass spectra were obtained on a Nippon Denshi
JMS-HX110A Ultrahigh Performance Mass Spectrometer at 75 eV
using a direct-inlet system. Elemental analyses were performed by
Yanaco MT-5.
Materials
distal-25,27-Bis(benzyloxy)-26,28-dihydroxy-5,11,17,23-tetra-
tert-butyl-2,8,14,20-tetrathiacalix[4]arene distal-2 was prepared
according to the reported procedure.7,11
Conclusions
:HꢀKDYHꢀGHPRQVWUDWHGꢀIRUꢀWKHꢀ¿UVWꢀWLPHꢀWKDWꢀWKHꢀVWHUHRVHOHFWLYHꢀ
synthesis of distal-bis{[(5'-methyl-2,2'-bipyridyl)-5-yl]methoxy}
tetrathiacalix[4]arene 4 with 1,3-alternate conformation has
Synthesis of 5-bromomethyl-5'-methyl-2,2'-bipyridine: A solution
of 5,5'-dimethyl-2,2'-bipyridine (500 mg, 2.84 mmol, 1 equiv.),

JOURNAL OF CHEMICAL RESEARCH 2009 107
N-bromosuccinimide (NBS) (556 mg, 3.12 mmol, 1.1 equiv.) and
2,2'-azobis(2,4-dimethylpentanenitrile) (V65) (300 mg, 1.20 mmol,
0.44 equiv.) in CH2Cl2ꢊꢁꢇꢇꢀP/ꢋꢀZDVꢀUHÀX[HGꢀXQGHUꢀDUJRQꢀIRUꢀꢁꢌꢀKꢄꢀ
The reaction mixture was allowed to rise to room temperature and
solvent was evaporated. The residue dissolved in hot hexane and the
VROLGꢀSDUWꢀRIIꢀRXWꢄꢀ7KHꢀ¿OWUDWHꢀSDUWꢀNHHSꢀꢉꢀKꢀDWꢀURRPꢀWHPSHUDWXUHꢀWKHQꢀ
GLEURPRPHWK\OꢀGHULYDWLYHVꢀZDVꢀSUHFLSLWDWHGꢀDQGꢀVHSDUDWHGꢀE\ꢀ¿OWUDWLRQꢄꢀ
7KHꢀ¿OWUDWHꢀSDUWꢀDJDLQꢀUHGXFHVꢀRQHꢆWKLUGꢀYROXPHꢀDQGꢀSXWꢀꢁꢌꢀKꢀDWꢀURRPꢀ
temperature and then white solid appears, which was recrystallisation
from ethyl acetate–hexane(1:1) gave pure product as a white powder
433 mg (58%); m.p. 85–87°C; GH (CDCl3): 2.39 (3H, s, BipyCH3),
4.53 (2H, s, –CH2Br), 7.62 (1H, d, J = 7.8 Hz, BipyH4'), 7.83 (1H,
d, J = 6.0 Hz, bipyH4), 8.28(1H, d, J = 7.8 Hz, BipyH3'), 8.35 (1H, d,
J = 8.4 Hz, BipyH3), 8.49 (1H, s, BipyH6') and 8.65(1H, s, BipyH6);
m/z: 262, 264 (M+) Found: C, 54.97; H, 4.42; N, 10.88. C12H11BrN2
(263.14) requires C, 54.77; H, 4.21; N, 10.65%.
Benzylation of 1 with benzyl bromide in the presence of Na2CO3:
Amixture of 1 (200 mg, 0.276 mmol) and Na2CO3 (293 mg, 2.8 mmol)
LQꢀ DFHWRQHꢀ ꢊꢁꢍꢀ P/ꢋꢀ ZDVꢀ KHDWHGꢀ DWꢀ UHÀX[ꢀ IRUꢀ ꢁꢀ Kꢄꢀ %HQ]\Oꢀ EURPLGHꢀ
ꢊꢇꢄꢈꢉꢀP/ꢃꢀꢌꢄꢎꢀPPROꢋꢀZDVꢀWKHQꢀDGGHGꢀDQGꢀWKHꢀPL[WXUHꢀKHDWHGꢀDWꢀUHÀX[ꢀ
for 17 h. After cooling the reaction mixture to room temperature,
LWꢀ ZDVꢀ ¿OWHUHGꢄꢀ 7KHꢀ ¿OWUDWHꢀ ZDVꢀ FRQFHQWUDWHGꢀ DQGꢀ WKHꢀ UHVLGXHꢀ ZDVꢀ
extracted with CH2Cl2 (100 mL u 2) and washed with water
(50 mL u 2), and dried (Na2SO4ꢋꢄꢀ7KHꢀ¿OWUDWHꢀZDVꢀFRQFHQWUDWHGꢀWRꢀ
give a yellow oil, which was then distilled under reduced pressure
to remove the excess unreacted benzyl bromide using a Kugelrohr
apparatus. The residue was washed with methanol to give the crude
distal-2 (247 mg, 98%) as a colourless solid. Recrystallisation from
MeOH:CHCl3 (3:1) gave 25,27-bis(benzyloxy)-26,28-dihydroxy-
5,11,17,23-tetra-tert-butyl-2,8,14,20-tetrathiacalix[4]arene, distal-2
as colourless prisms; m.p. 250–252°C; Qmax (KBr)/cm-1 3383 (OH),
2962, 2867, 1478, 1448, 1437, 1363, 1260, 1244, 886 and 756; GH
(CDCl3) 0.79 (18H, s, tBu), 1.34 (18H, s, tBu), 5.49 (4H, s, OCH2Ph),
6.96 (4H, s, ArH), 7.24–7.36 (6H, m, PhH), 7.61–7.64 (4H, m, PhH),
7.68 (4H, s, ArH) and 7.98 (2H, s, OH); m/z 901 (M+) Found: C,
72.08; H, 6.86. C54H60O4S4 (901.28) requires C, 71.96; H, 6.71%.
O-Alkylation of distal-2 with 5-bromomethyl-5'-methyl-2,2'-
bipyridine 3 in the presence of Cs2CO3: A mixture of distal-2
(200 mg, 0.22 mmol) and Cs2CO3 (720 mg, 2.22 mmol) in dry
DFHWRQHꢀꢊꢁꢍꢀP/ꢋꢀZDVꢀKHDWHGꢀDWꢀUHÀX[ꢀIRUꢀꢁꢀKꢀXQGHUꢀ12. A solution
of 5-bromomethyl-5'-methyl-2,2'-bipyridine 3 (353 mg, 1.34 mmol)
LQꢀ '0)ꢀ ꢊꢍꢀ P/ꢋꢀ ZDVꢀ WKHQꢀ DGGHGꢀ DQGꢀ WKHꢀ PL[WXUHꢀ KHDWHGꢀ DWꢀ UHÀX[ꢀ
for an additional 20 h. After cooling the reaction mixture to room
WHPSHUDWXUHꢃꢀLWꢀZDVꢀDFLGL¿HGꢀZLWKꢀꢁꢀ0ꢀ+&OꢀꢊꢁꢇꢀP/ꢋꢀDQGꢀH[WUDFWHGꢀ
with CH2Cl2 (100 mL u 2). The combined extracts were washed
with water (50 mL u 2), and dried (Na2SO4) and condensed under
reduced pressure to give a yellow oil. The residue was washed with
methanol to give 1,3-alternate-4 (198 mg, 68%) as a colourless solid.
Recrystallisation from MeOH:CHCl3 (3:1) gave 1,3-alternate-4 as a
colourless prisms.
prisms; m.p. 81–82°C; GH (CDCl3) 1.30 (9H, s, tBu), 2.30 (6H, s,
CH3), 2.40 (3H, s, BipyCH3), 4.87 (2H, s, OCH2), 7.04 (2H, s, ArH),
7.63 (1H, dd, J = 8.1, 1.8 Hz, BipyH4'), 7.91 (1H, dd, J = 8.1, 1.8 Hz,
BipyH4), 8.30 (1H, d, J = 8.1 Hz, BipyH3'), 8.39 (1H, d, J = 8.1 Hz,
BipyH3), 8.51 (1H, d, J = 1.8 Hz, BipyH6') and 8.75 (1H, d,
J = 1.8, BipyH6); m/z: 360 (M+) Found: C, 80.05; H, 7.79; N, 7.68.
C24H28N2O (360.50) requires C, 79.95; H, 7.83; N, 7.77%.
O-Alkylation of distal-2 with N,N-diethylchloroacetamide in the
presence of Cs2CO3: A mixture of distal-2 (680 mg, 0.754 mmol) and
Cs2CO3 (2.46 g, 7.54 mmol) in dry acetone (30 mL) was heated at
UHÀX[ꢀIRUꢀꢁꢀKꢀXQGHUꢀ12. A solution of N,N-diethylchloroacetamide 7
ꢊꢁꢄꢁꢈꢀJꢃꢀꢂꢄꢍꢉꢀPPROꢋꢀZDVꢀWKHQꢀDGGHGꢀDQGꢀWKHꢀPL[WXUHꢀKHDWHGꢀDWꢀUHÀX[ꢀ
for an additional 17 h. After cooling the reaction mixture to room
WHPSHUDWXUHꢃꢀLWꢀZDVꢀDFLGL¿HGꢀZLWKꢀꢁꢀ0ꢀ+&OꢀꢊꢁꢇꢀP/ꢋꢀDQGꢀH[WUDFWHGꢀ
with CH2Cl2 (100 mL u 2). The combined extracts were washed
with water (50 mL u 2), and dried (Na2SO4) and condensed under
reduced pressure to give a yellow oil. The residue was washed with
methanol to give 1,3-alternate-8 (510 mg, 60%) as a colourless solid.
Recrystallisation from MeOH:CHCl3 (3:1) gave 1,3-alternate-8 as a
colourless prisms.
1,3-alternate-25,27-Bis(benzyloxy)-26,28-bis[(N,N-diethylamino-
carbonyl)methoxy]-5,11,17,23-tetra-tert-butyl-2,8,14,20-tetrathiacalix
[4]arene (1,3-alternate-8) was obtained as colourless prisms, m.p.
255–256°C; Qmax (KBr)/cm-1 1664; GH (CDCl3) 0.83 (18H, s, tBu),
0.89–1.00 (6H, m, CH2CH3), 1.10–1.20 (6H, m, CH2CH3), 1.30 (18H,
s, tBu), 3.12–3.19 (4H, m, CONCH2), 3.35–3.42 (4H, m, CONCH2),
4.70 (4H, s, CH2CON), 4.95 (4H, s, CH2Ph), 7.18 (4H, s, ArH), 7.17–
7.23 (10H, m, PhH) and 7.62 (4H, s, ArH); m/z 1127.5 (M+) Found:
C, 70.25; H, 7.28; N, 2.44. C66H82N2O6S4 (1127.74) requires C, 70.3;
H, 7.33; N, 2.48%.
Extraction experiments
Metal picrates (2.5 u 10-4 M) were prepared in situ by dissolving the
metal hydroxide (0.01 mol) in 2.5 u 10-4 M picric acid (100 mL); triply
distilled water was used for all aqueous solutions. Two-phase solvent
extraction was carried out between water (5 mL, [metal picrate]
= 2.5 u 10-4 M) and CH2Cl2 (5 mL, [ionophore] = 2.5 u 10-4 M).
7KHꢀ WZRꢆSKDVHꢀ PL[WXUHꢀ ZDVꢀ VKDNHQꢀ LQꢀ Dꢀ VWRSSHUHGꢀ ÀDVNꢀ IRUꢀ
ꢌꢀ Kꢀ DWꢀ ꢌꢍꢀƒ&ꢄꢀ :Hꢀ FRQ¿UPHGꢀ WKDWꢀ WKLVꢀ SHULRGꢀ LVꢀ VXI¿FLHQWꢀ WRꢀ DWWDLQꢀ
the distribution equilibrium. This was repeated three times, and the
solutions were left standing until phase separation was complete.
The extractability was determined spectrophotochemically from the
decrease in the absorbance of the picrate ion in the aqueous phase as
described by Pedersen.44
Stoichiometry of metal complexation
The method of continuous variation44 was employed to determine the
stoichiometry of 1,3-alternate-4. Two-phase solvent extraction was
carried out between aqueous picrates (5 mL, [silver picrate] = 2 u
10-4 M) and 1,3-alternate-4 (5 mL, [1,3-alternate-4] = 2 u 10-4
M
1,3-alternate-25,27-Bis(benzyloxy)-26,28-bis{[(5'-methyl-2,2'-
bipyridinyl)-5-yl]methoxy}-5,11,17,23-tetra-tert-butyl-2,8,14,20-
tetrathiacalix[4]arene (1,3-alternate-4) was obtained as colourless
prisms, m.p. 253–255°C; Qmax (KBr)/cm-1 3468, 2962, 1653, 1558,
1471, 1375, 1265, 1085, 1015 and 827; GH (CDCl3) 0.78 (18H,
s, tBu), 0.86 (18H, s, tBu), 2.38 (6H, s, BipyCH3), 5.06 (4H, s,
OCH2Ph), 5.36 (4H, s, OCH2Bipy), 6.92 (4H, d, J = 9.0 Hz, PhH),
6.97–7.02 (6H, m, PhH), 7.07 (4H, s, ArH), 7.11 (4H, s, ArH), 7.53
(2H, d, J = 6.0 Hz, BipyH4'), 7.56 (2H, d, J = 6.0 Hz, BipyH4), 8.16
(2H, s, BipyH6'), 8.25 (2H, d, J = 6.0 Hz, BipyH3'), 8.28 (2H, d,
J = 6.0 Hz, BipyH3) and 8.49 (2H, s, BipyH6); m/z 1265.52 (M+)
Found: C, 73.37; H, 6.32; N, 4.23. C78H80N4O4S4 (1265.77) requires
C, 74.01; H, 6.37; N, 4.43%.
in CH2Cl2). The molar ratios of the both 1,3-alternate-4 and metal
picrate were varied from 0 to 1, while the total concentration was
kept at several constant levels. The two-phase mixture in a glass tube
immersed in a thermostated water bath at 25°C was shaken at 300
strokes per min for 1 h and then kept, at the same temperature, for 2 h,
allowing the complete separation of the two phases. The absorbance
of each solution was determined by UV spectroscopy (O = 290 nm).
Job plots were generated by plotting the extracted [Ag+] versus the
mole fraction of metal.
1H NMR complexation experiments
To a CDCl3 solution (4 u 10-3 M) of 1,3-alternate-4 in the NMR tube
was added a CD3CN solution (4 u 10-2 M) of AgClO4 and KSO3CF3.
The spectrum was registered after addition and the temperature of
NMR probe kept constant at 25°C.
Similarly, O-alkylation of distal-2 with 5-bromomethyl-5'-methyl-
2,2'-bipyridine 3 in the presence of NaH or K2CO3 afforded 1,3-
alternate-4 in 55 and 59% yields, respectively.
Preparation
of
4-tert-butyl-2,6-dimethyl{[(5'-methyl-2,2'-
The 1H NMR data of the most representative complexes is given
below.
bipyridinyl)-5-yl]methoxy}benzene 6: A mixture of 4-tert-butyl-
2,6-dimethylphenol 529 (400 mg, 2.25 mmol) and NaH (580 mg,
ꢁꢉꢄꢍꢀPPROꢃꢀꢏꢇꢀZWꢅꢋꢀLQꢀGU\ꢀ7+)ꢀꢊꢌꢇꢀP/ꢋꢀZDVꢀKHDWHGꢀDWꢀUHÀX[ꢀIRUꢀ
1 h under N2. Then a solution of 5-bromomethyl-5'-methyl-2,2'-
bipyridine 3 was added at room temperature and the mixture heated
DWꢀUHÀX[ꢀIRUꢀDQꢀDGGLWLRQDOꢀꢁꢂꢀKꢄꢀ$IWHUꢀFRROLQJꢀWKHꢀUHDFWLRQꢀPL[WXUHꢀ
WRꢀ URRPꢀ WHPSHUDWXUHꢃꢀ LWꢀ ZDVꢀ DFLGL¿HGꢀ ZLWKꢀ ꢁꢀ 0ꢀ +&Oꢀ ꢊꢁꢇꢀ P/ꢋꢀ DQGꢀ
extracted with CH2Cl2 (100 mL u 2). The combined extracts were
washed with water (50 mL u 2), dried (Na2SO4) and condensed under
reduced pressure to give a yellow oil. The residue was treated with
MeOH (5 mL) to give the crude 6 (373 mg, 46%) as a white solid.
Recrystallisation from CHCl3:MeOH (3:1) gave 6 as colourless
1,3-alternate-4ŠAgꢀꢁ (1:1): GH (CDCl3ꢀCD3CN, 10:1) 0.79 (18H,
s, tBu), 0.84 (18H, s, tBu), 2.53 (6H, s, BipyCH3), 5.07 (4H, s,
OCH2Ph), 5.16 (4H, s, OCH2Bipy), 6.98 (4H, s, ArH), 6.92 (4H, d,
J = 9.0 Hz, PhH), 7.05–7.10 (6H, m, PhH), 7.17 (4H, s, ArH), 7.96
(4H, d, J = 6.0, Bipy-H4, H4'), 8.02 (2H, s, BipyH6'), 8.22 (2H, dd,
J = 6.0, BipyH3'), 8.26 (2H, d, J = 6.0 Hz, BipyH3) and 8.36 (2H, s,
BipyH6).
1,3-alternate-8ŠAgꢀꢁ(1:1): GH (CDCl3ꢀCD3CN, 10:1) 0.82 (18H,
s, tBu), 1.18–1.24 (6H, m, CH2CH3), 1.29–1.33 (6H, m, CH2CH3),
1.20 (18H, s, tBu), 3.25–3.35 (4H, m, CONCH2), 3.45–3.55 (4H, m,
CONCH2), 4.76 (4H, s, CH2CON), 5.13 (4H, s, CH2Ph), 6.94 (4H, d,

108 JOURNAL OF CHEMICAL RESEARCH 2009
15 T. Nabeshima, Y. Yoshihira, T. Saiki, S. Akine and E. Horn, J. Am. Chem.
Soc., 2003, 125, 28.
J = 7.0 Hz, PhH2), 7.11 (4H, dd, J = 7.0, 7.0 Hz, PhH3), 7.16 (4H, s,
ArH), 7.21 (2H, t, J = 7.0 Hz, PhH4) and 7.37 (4H, s, ArH).
16 T. Nabeshima, T. Saiki and K. Sumitomo, Org. Lett., 2002, 4, 3207.
17 P.D. Beer, J.P. Martin and M.G.B. Drew, Tetrahedron, 1992, 48, 9917.
18 A. Casnati, C. Fischer, M. Guardigli, A. Isernia, I. Manet, N. Sabbatini
and R. Ungaro, J. Chem. Soc., Perkin Trans. 2, 1995, 395.
19 S. Pellet-Rostaing, V.J.-B. Regnouf, R. Lamartine and B. Fenet, Inorg.
Chem. Commun., 1999, 2, 44.
Determination of association constants
The measurements were performed by 1H NMR titration experiments
in CDCl3:CD3CN 1:1 v/v) at 25°C using a concentration of 4 u 10-3
M and a varying guest concentration of 0.3–30 mM. The association
constants (Kass) for the 1,3-alternate-4 complexes were calculated
by QRQꢆOLQHDUꢀ¿WWLQJꢀDQDO\VLVꢀRIꢀWKHꢀREVHUYHGꢀFKHPLFDOꢀVKLIWꢀRIꢀWKHꢀ
methylene protons of OCH2Bipy for 1,3-alternate-4ŠAg+ complex
and 1,3-alternate-4ŠK+ complex, respectively.43
20 V.J.-B. Regnouf, J.-O. Dalbavie, R. Lamartine and B. Fenet, Tetrahedron
Lett., 2001, 42, 2681.
21 N. Psychogios and V.J.-B. Regnouf, Tetrahedron Lett., 2001, 42, 2799.
22 N. Psychogios and V.J.-B.Regnouf, Tetrahedron Lett., 2002, 43, 77.
23 T. Nabeshima, Coord. Chem. Rev., 1996, 148, 151.
24 B. Linton and A.D. Hamilton, Chem. Rev., 1997, 97, 1669.
25 T. Nabeshima, S. Akine and T. Saiki, Rev. Heteroatom Chem., 2000, 22,
219.
Received 8 October 2008; accepted 25 November 2008
Paper 08/0213 doi: 10.3184/030823409X396436
Published online: 24 February 2009
26 F. Vögtle, Cyclophane Chemistry, John Wiley & Sons Ltd., 1993.
27 M. Tashiro and T. Yamato, J. Org. Chem., 1981, 46, 4556.
28 M. Tashiro and T. Yamato, J. Org. Chem., 1983, 48, 1461.
29 T. Yamato, S. Rahman, Z. Xi, F. Kitajima and J. Tae Gil, Can. J. Chem.,
2006, 84, 58–64.
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