Synthesis of amidocrownophanes with 27- and 28-membered rings and their molecular recognition toward urea and its derivatives

Article abstract of DOI:10.1002/jhet.5570420416

Novel crownophanes with 27- and 28-membered rings having two hydroxyl groups, two amide groups, and aromatic moieties such as naphthalene, pyridine, and phenyl rings were successfully synthesized by a one-step reaction from the corresponding macrocyclic p

Full text of DOI:10.1002/jhet.5570420416

May-Jun 2005
575
Synthesis of Amidocrownophanes with 27- and 28-Membered Rings
and Their Molecular Recognition toward Urea and its Derivatives
Shamsun Naher, Kazuhisha Hiratani*, Michinori Karikomi, and Kazuo Haga
*Department of Applied Chemistry, Faculty of Engineering,
Utsunomiya University, 7-1-2 Youtou, Utsunomiya 321-8585, Japan.
Fax: +81-(0)28-689-6146; E-mail: hiratani@cc.utsunomiya-u.ac.jp
Received October 21, 2004
Novel crownophanes with 27- and 28-membered rings having two hydroxyl groups, two amide groups,
and aromatic moieties such as naphthalene, pyridine, and phenyl rings were successfully synthesized by a
one-step reaction from the corresponding macrocyclic polyethers via "tandem Claisen rearrengement" in
moderate yields. They can solubilize urea and its derivatives into chloroform solution, while the corre-
sponding macrocyclic polyethers do not solubilize them. According to NMR studies, crownophanes 1 and
2 interact with urea and its derivatives forming 1:1 complexes.
J. Heterocyclic Chem., 42, 575 (2005).
and accepting groups existing within the macrocycles
can form H-bonding with guest molecules. In particular,
introduction of amide groups is expected to result in
strengthening of hydrogen bonding for the specific
guests.
Introduction.
Macrocycles which have rigid aromatic moieties and
flexible oligoethylene glycol parts within the macrocyclic
rings are called "crownophanes" [1]. These structurally-
hybridized macrocycles are expected to exhibit special
functions or properties which are different from those of
basic macrocycles such as crown ethers [2], cyclophanes
[3], calixarenes [4], and spherands [5].
In one of the first papers on crown ether chemistry,
Pedersen showed that urea interacts with simple crown
ethers such as benzo-18-crown-6 [21]. After that,
although there have been reported many macrocycles
which can exhibit molecular recognition with neutral mol-
ecules, there is no report of macrocyclic receptor as shown
in Figure 1. Using our designed and synthesized macro-
cyclic receptor having both proton donating and accepting
groups, we investigated their molecular recognition prop-
erties with some neutral organic guest molecules such as
urea and urea derivatives. As guest species of urea deriva-
tives, we selected thiourea, ethylene urea, propylene urea
and glutarimide for complexation.
Several interesting properties of crownophanes having
one or more phenol moieties have been reported so far [6-
8]. Furthermore, they are extensively studied from the
viewpoints of molecular recognition, artificial catalysts,
supramolecular structures and so on [9]. In order to realize
the molecular recognition, the design of host molecules for
specific guests is one of the most important points.
Although most of the complexation studies with crown
ethers starting from the pioneering work by Pedersen [10]
have concentrated on metal cations [11], organic cations
[12] and anions [13] as the guest species, there is also a
significant interest in the complexation of neutral mole-
cules [14]. In the biological systems, weak interactions
such as H-bonding, van der Waals forces and electrostatic
interactions are mainly responsible for complexation of
receptors with organic substrates. In particular, H-bonding
plays a very important role in the molecular recognition
toward organic molecules. Therefore, precise design of
host molecules exhibiting H-bonding ability is very impor-
tant in these kinds of studies.
Figure 1. Molecular recognition using multi-H bonding interactions.
In our work, we designed and succeeded in synthesiz-
ing crownophane type derivatives 1, 2 and 3 via "tandem
Claisen rearrangement (TCR)"[15-20] which consist of
27- and 28-membered rings containing cyclophane and
oligoethylene glycol units, two hydroxyl groups and two
amide groups. Moreover, pyridine or phenyl group is
introduced into the macrocycles as a part of the ring.
They could be expected to exhibit high affinity and good
selectivity not only for ionic guest species but also for
neutral organic molecules, because both proton donating
Results and Discussion.
Synthesis of Amidocrownophanes.
In this study, we prepared three amidocrownophanes
1~3 in order to compare either the hetero atom effect or
ring size effect, where 1 and 2 have a 28-membered and 3
has a 27-membered ring.

576
S. Naher, K. Hiratani, M. Karikomi, and K. Haga
Vol. 42
Figure 2. Structures of 28-membered and 27-membered ring crownophanes.
The 28-membered macrocyclic polyether 7 was pre-
cyclic polyethers, 7, 11 and 12 at 160 ºC, 3.5 hrs in N-
methyl-2-pyrrolidinone (NMP), the corresponding
crownophanes 1-3 were successfully obtained in moderate
yields, respectively.
pared from diamine 6 and 2,6-pyridinedicarbobonyl
dichloride under high dilution conditions as shown in
Scheme 1. To find out the role of the nitrogen atom of the
pyridyl group, a macrocycle having an m-phenylene group
was introduced for comparison. Macrocyclic polyether 11
was obtained by the reaction between ditosylate 10 and 2-
methylene-1,3 bis(3-hydroxynaphthyl-2-oxy)propane (4)
1
From the H NMR spectra shown in Figures 2, 3 and 4,
it is clear that macrocycles 7, 11 and 12 were successfully
converted into crownophanes 1, 2 and 3 by thermal reac-
tion, relatively. After tandem Claisen rearrangement
(TCR), chemical shifts and line shapes of the proton
signals changed drastically, and new peaks appeared due
to the phenolic OH protons in the NMR spectra. The
peaks based on the isobutenyl unit shifted upfield signifi-
cantly, attributed to the formation of C-isobutenyl bonds
from O-isobutenyl bonds. Products 1, 2 and 3 were con-
using Cs CO and KI in DMF under high dilution condi-
2
3
tions as shown in Scheme 2. Furthermore, in order to find
out the effect of the introduced benzene moiety, macrocy-
cle 12 was prepared in a similar manner by the reaction of
6 with phthalic acid dichloride under high dilution condi-
tions (see Scheme 1). By thermal reaction of the macro-
Scheme 1
Synthetic route of novel crownophanes via macrocyclic polyethers.

May-Jun 2005
Synthesis of Amidocrownophanes with 27- and 28-Membered Rings
577
Scheme 2
Synthetic route of novel crownophanes 2 and 11.
1
firmed by ESI mass, H NMR spectral data, IR spectral
data and elemental analysis. In the elemental analysis it
was observed that products 1-3 contain H O molecules.
2
This is probably because they preferably form H-bonding
with H O for the existence of hydroxyl groups, amide
2
groups and ether oxygen atoms into the crownophanes.
Complexation with Urea and its Derivatives.
We tested the interaction of macrocycles 1~3, 7, 11 and
12 with urea and urea derivatives such as thiourea, propy-
lene urea, ethylene urea and glutarimide using the NMR
1
Figure 3. H NMR spectra of crownophanes 11 (before TCR) and 2 (after
TCR).
technique. In each of the NMR sample tubes, we mixed
up the macrocycles and the guest species in CDCl
3
respectively. After sonification, and keeping the sample
1
tubes overnight, we measured their H NMR and obtained
the following results, which are shown in Tables 1 and 2.
The chemical shifts of amidocrownophanes 1 and 2
clearly changed when adding guest molecules, while
amidocrownphane 3 and crown ether derivatives before
1
Figure 2(Second Fig 2). H NMR spectra of crownophanes 7 (before
TCR) and 1(after TCR).

578
S. Naher, K. Hiratani, M. Karikomi, and K. Haga
Vol. 42
1
Figure 4. H NMR spectra of crownophanes 12 (before TCR) and 3(after TCR).
Table 1
1H NMR Chemical Shift Values Between Free Ligand (1) and Ligand (1) with Guest Molecules
H
H
O
Ligand 1 /
Ligand 1 with guest
molecules.
Ethylene
glycol chain -NH-
Ar-O-CH2-
CH2-O
*2
Chemical
shift of
Guest
H
H
H
H
OH
H
C
H
CH2-
CH2-O
O
N
H
O
Molecules
H
N
C
*2
4.55
(2H, s)
3.69
(4H, s)
7.06
(2H, s)
4.39
(4H, m)
3.64
(12H, m)
8.55
(2H, s)
8.00(1H, t)
8.37(2H, d)
O
O
O
N
H
OH
OH
N
H
N
O
O
O
1
NH2
4.48
4.34
4.48
3.77
3.81
3.76
*1
*1
4.36
3.72
3.68
3.73
3.70
8.95
8.71
9.02
7.98
8.35
6.93 (N-H)
5.91 (N-H)
4.85 (N-H)
O
S
1
+
+
NH2
NH2
4.34
3.79
8.00
8.37
1
NH2
7.18
4.35
7.97
8.32
HN
3.30 (N-CH2)
O
1
+
1.87 (C-CH2-C)
HN
H
N
4.49
4.49
3.76
3.78
*1
4.35
3.70
3.65
8.86
8.88
7.95
8.32
Undetected (N-H)
O
1 +
N
H
7.15
4.36
7.95
8.30
8.53 (N-H)
O
1
+
HN
O
*1 After addition of guest molecules, peak of hydroxyl groups of the ligand 1 was disappeared. This is probably due to the severe
broadening of hydroxyl groups after complexation; *2 Values of the chemical shifts are taken in the center of the peaks.

May-Jun 2005
Synthesis of Amidocrownophanes with 27- and 28-Membered Rings
579
TCR 7, 11, and 12 did not show any change in the NMR
spectrum by adding urea and urea derivatives. This phe-
nomenon shows the lack of strong electron donating com-
ponents such as hydroxyl groups, which are formed after
the "tandem Claisen rearrangement (TCR)". Surprisingly,
3 was the only compound where no change in the NMR
spectra was observed when adding urea and urea deriva-
tives among crownophanes, 1~3. Therefore, it is assumed
that there is some structural effect among them.
cal shifts of –OH groups. NH protons of amide groups
also showed downfield chemical shifts after the incorpo-
ration of guest species. In addition, new peaks were
observed based on the amino protons and the methylene
protons of the guest molecules.
1
H NMR titration experiment of crownophane 2 and
ethylene urea as guest was carried out in CDCl . From the
3
chemical shift data, it was shown that the complexation of
ligand 2 with ethylene urea gives only one species of the
Table 2
1H NMR Chemical Shift Values Between Free Ligand (2) and Ligand (2) with Guest Molecules
H
H
O
Ligand 2 /
Ligand 2 with guest
molecules.
Ethylene
glycol chain
Ar-O-CH2-
CH2-O
Chemical
shift of
Guest
H
H
C
H
H
OH
H
C
O
-NH-CH2-
CH2-O
*2
O
N
H
H
Molecules
H
H
4.41
(2H,s)
3.69
(4H, s)
6.90
(2H, s)
4.37 (m)
3.83 (m)
3.68 (m)
6.89
(2H, t)
8.35 (1H, s)
7.76(2H, d)
7.32 (1H, t)
O
O
O
N
H
OH
OH
H
N
O
O
O
2
NH2
4.40
4.39
4.40
4.39
4.40
3.72
3.70
3.73
3.70
3.71
6.93
7.02
7.20
*1
4.35
3.84
3.68
3.70
7.11
6.98
7.197
7.03
7.16
8.34
7.77
7.31
8.33
7.76
7.30
8.39
7.83
7.35
8.35
7.77
7.38
8.38
7.81
7.34
4.83 (N-H)
6.27 (N-H)
2 + O
NH2
NH2
NH2
4.36
3.85
S
2 +
HN
4.35
3.86
3.71
3.73
5.00 (N-H)
O
2 +
3.23~3.27(N-CH2-)
1.87 (C-CH2-C)
Undetected (N-H)
HN
HN
4.36
3.84
3.70
3.71
2 + O
HN
O
7.07
3.89
8.48 (N-H)
HN
O
2
+
*1 It was not possible to detect the chemical shift of hydroxyl group probably due to the severe broadening after addition of guest molecule; *2
Values of the chemical shifts are taken in the center of the peaks.
In fact, protons of these groups obviously shifted in the
H NMR spectra which are summarized in Tables 1 and 2.
1
The large chemical shift values were observed by the
complexation of the crownophane 1 with urea and propy-
lene urea. Propylene urea is soluble in CDCl , however
3
after complaxation, the chemical shift of amino groups
and methylene groups change to downfield shift {NH : δ:
4.85 ppm (in the case of 1), 5.00 ppm (in the case of 2),
-CH -; δ: 1.87 ppm}. The chemical shift of the amide pro-
2
tons of crownophane 1 drastically changes to downfield
shift (δ: 9.02 ppm) compared to the amide protons of the
free ligand (δ : 8.55 ppm). Similarly, the OH protons of
ligand 1 change from δ: 7.06 to 7.18 ppm probably due to
1
complexation between them. On the other hand, in the H
NMR spectrum of crownophane 2, the OH protons after
1
Figure 5. H NMR spectra of complexation between ligand 1 and
complexation with the guests, showed downfield chemi-
propylene urea

580
S. Naher, K. Hiratani, M. Karikomi, and K. Haga
Vol. 42
does not have that ability at all. The host molecules 1 and
2 with incorporation of the ability for bio-molecules and
their derivatives are expected to be used for molecular sen-
sor and separating reagent.
EXPERIMENTAL
General Procedure.
Commercially available reagents were purchased from Wako,
Aldrich, TCI, and Cica, and used without further purification.
Melting points were taken on Micro melting point apparatus and
1
are not corrected. H NMR spectra were recorded with a Varian
(300MHz) spectrometer in CDCl using TMS as an internal stan-
3
dard. All chemical shifts are given in parts per million relative to
tetramethylsilane (δ, 0.00 ppm). Electrospray ionization mass
spectra (ESI-MS) were performed in the following conditions: a
-1
sample solution was sprayed at a flow rate of 2 µL min at the tip
of needle biased by a voltage of 4.5 KV higher than that of a
counter electrode. IR spectra were obtained on a FT/IR-430 spec-
trometer. Elemental analyses were obtained on a Fisons EA1108
CHNS-O. The silica gel for the column chromatography was
from Cica-silica gel 60 (63-210 µm). The progress of the reac-
1
Figure 6. H NMR spectra of complexation between ligand 2 and ethyl-
ene urea.
tions was followed by TLC using Merck silica gel 60 F
.
254
complex. Figure 7 shows that ligand 2 forms 1:1 complex
with ethylene urea.
Synthesis of Macrocyclic Polyether 7.
In conclusion, we have synthesized novel 28-membered
Solutions (100 ml THF) of diamine 6 (1.83 mmol) and 2,6-
pyridinedicarbobonyl dichloride (1.83 mmol) were simultane-
ously added dropwise to the solution of THF (350 ml) containing
ring size crownophanes 1 and 2 acting as the receptor for
neutral guest molecules such as urea and urea derivatives
based on the rigid disposition of hydrogen bonding groups
Et N (3.65 mmol) as a base at 50 ºC in 5-6 hours. After the addi-
3
tion was complete, the reaction mixture was stirred overnight.
The solvent was removed under reduced pressure. The residue
was dissolved in CHCl , washed with H O and dried over anhy-
3
2
drous Na SO . After evaporation of CHCl , the residue was sub-
2
4
3
jected to column chromatography on silica gel using
AcOEt:CHCl (1:3) as an eluent. Further purification was per-
3
formed using GPC (Gel Permeation Column Chromatography)
with CHCl as an eluent. Macrocycle 7 was obtained as the main
3
1
product. Colorless solid; yield 39%; R =0.28; m.p. 86-87 ºC; H
f
NMR: δ 3.39 (CH -NH, 4H, m), 3.55 (O-CH -CH -NH, 4H, m),
2
2
2
3.73 (O-CH -CH -, 4H, m), 4.19 (Ar-O-CH -CH , 4H, m), 4.90
2
2
2
2
(=C-CH -O, 4H, s), 5.39 (C=CH , 2H, s), 7.09 (Ar-H, 2H, s),
2
2
7.18 (Ar-H, 2H, s), 7.3(Ar-H, 4H, m), 7.6(Ar-H, 4H, m), 7.81(Py-
H, 1H, t, 8Hz), 8.17 (Py-H, 2H, d, 8Hz), 8.73(NH, 2H, broad); IR
-1
(KBr, ν/cm ): 1663, 1509, 1485, 1258, 1115. ESI-Mass: Calcd.
+
+
for C H N O , [M + Na ]: 700.27. Found: [M + Na ]: 700.4.
39 39
3 8
Anal. Calcd. for C H N O •H O: C,68.21; H, 5.87; N, 6.12.
39 39
3
8
2
Found: C, 67.98; H, 6.05; N, 5.94.
1
Synthesis of Macrocyclic Polyether 11.
Figure 7. H NMR titration experiment between ligand 2 as host and
ethylene urea as guest.
Cesium carbonate (5.28 mmol), KI (catalytic amount) were
placed into a round bottomed flask in dry DMF (300 ml). The
flask was placed in the oil bath and was warmed at 70 ºC with
stirring. 2-Methylene-1,3-bis (3-hydroxynapthyl-2-oxy)propane
(4) (2.15 mmol), and compound 10 (2.33 mmol) were dissolved
in dry DMF (100 ml) and were placed into an automatic magnetic
dropping funnel. The solution was added dropwise over a period
of 15 min. Reaction was continued for 3 days maintaining the
temperature at 70 ºC. After removal of the solvent under vac-
in the interior of the macrocyclic scaffold. On the con-
trary, crownophanes 7, 11 and 12 have no complexation
ability due to the absence of hydroxyl groups indicating
that these groups play an important role in the formation of
strong complexes. We also have shown the ability of
crownophanes 1 and 2 to dissolve urea and thiourea into
the less polar solvent chloroform, whereas crownophane 3
uum, the residue was extracted with CHCl , washed with H O
3
2
and dried over anhydrous Na SO . After evaporation of CHCl ,
2
4
3

May-Jun 2005
Synthesis of Amidocrownophanes with 27- and 28-Membered Rings
581
the macrocyclic polyether 11 was isolated by column chromatog-
raphy eluted with AcOEt: CHCl (1:3) followed by GPC eluted
+
+
for C H N O , [M + Na ]: 699.28. Found: [M + Na ]: 699.4.
40 40
2 8
3
Anal. Calcd. for C H N O •H O: C, 69.15; H, 6.09; N, 4.03.
40 40 2 8 2
with CHCl . Pale yellow solid; yield 38%; R = 0.17; m.p. 85-86
3
f
Found: C, 68.80; H, 5.86; N, 4.19.
1
ºC; H NMR: δ 3.43~3.48 (N-CH -, 4H, m), 3.59~3.62 (-O-
2
Synthesis of Crownophane 3.
CH -, 4H, m), 3.87~3.89 (-O-CH -, 4H, m), 4.27~4.29
2
2
(Ar-O-CH -, 4H, m), 4.60 (=C-CH -O-, 4H, s), 5.22
Procedure is the same as that described for crownophane 1.
White solid; yield 45%; Rf = 0.1 ; m.p. 192-193 ºC; H NMR: δ
2
2
1
(C=CH , 2H, s), 7.15 (Ar-H, 4H, s), 7.20 (Ar-H, 1H, t,
2
8Hz), 7.21 (NH, 2H, broad), 7.31~7.35 (Ar-H, 4H, m),
7.57 (Ar-H, 2H, d, 7Hz), 7.66 (Ar-H, 2H, d, 7Hz), 7.85
3.66~3.76 (=C-CH -O, CH -NH & CH -O, 4H, m), 3.84~3.90
2
2
2
(O-CH , 4H, m), 4.26~4.32 (C=CH & Ar-O-CH , 6H, m), 7.09
2
2
2
-1
(Ar-H, 2H, d, 8Hz), 8.15 (Ar-H, 1H, s); IR (KBr, ν/cm ):
(OH, 2H, broad), 7.12~7.16 ( Ar-H, 2H, m), 7.15 (Ar-H, 2H, s),
7.26~7.36 (Ar-H, 4H, m), 7.46~7.50 (Ar-H & NH, 4H, m), 7.65
1648, 1509, 1484, 1256, 1115. ESI-Mass: Calcd. for
+
+
13
C H N O , [M + Na ]: 699.28. Found: [M + Na ]: 699.4.
(Ar-H, 2H, d, 8Hz), 7.76 (Ar-H, 2H, d, 8Hz); C NMR: δ 32.03,
40 40
2 8
Anal. Calcd. for C H N O •H O: C, 68.28; H, 6.13; N, 3.98.
Found: C, 68.38; H, 6.10; N, 3.96.
68.12, 68.62, 69.99, 70.16, 109.28, 110. 40, 118.65, 123.27,
124.43, 127.13, 127.83, 128.66, 128.76, 129.86, 129.90, 130.86,
40 40
2
8
2
-
132.40, 135.10, 144.92, 145.75, 146.70, 167.75; IR (KBr, ν/cm
Synthesis of Macrocyclic Polyether 12.
1
): 2929, 1728, 1645, 1448, 1284, 1118. ESI-Mass: Calcd. for
+
+
Procedure is the same as that described for macrocyclic poly-
C H N O , [M + H ]: 677.28. Found: [M + H ]: 677.0
40 40
2 8
1
ether 7. White solid; yield 14 %, R = 0.19. m.p. 183-184 ºC; H
Anal. Calcd. for C H N O •H O: C, 69.15; H, 6.09; N, 4.03.
f
40 40
2
8
2
NMR: δ 3.44~3.48 (NH-CH -, 4H, m), 3.57~3.62(O-CH -CH -
Found: C, 68.87; H, 5.79; N, 4.14.
2
2
2
N, 4H, m), 3.82~3.88 (-CH -O-CH -, 4H, m), 4.22~4.25 (Ar-O-
2
2
Synthesis of Diamine 6.
CH -CH -O, 4H, m), 4.60 (=C-CH -O, 4H, s), 5.29 (C=CH , 2H,
2
2
2
2
s), 7.00~7.14 (Ar-H & NH, 6H, m), 7.3~7.4 (Ar-H, 6H, m),
Diamine was prepared from the reaction between 2-methyl-
ene-1,3-bis(3-hydroxynaphthyl-2-oxy)propane and 1-iodo-5-
pthalyl-glycol using KOBu-t as base in DMF at 70 ºC for 12
hours. After evaporating the solvent and extracting/washing the
reaction mixture by CHCl /H O, it was subjected to column
-
7.45~7.50 (Ar-H, 2H, m), 7.6~7.7 (Ar-H, 4H, m); IR (KBr, ν/cm
1
): 1651, 1508, 1485, 1257, 1114. ESI-Mass: Calcd. for
+
+
C H N O , [M + H ]:677.28. Found: [M + H ]: 677.0
40 40
2 8
Anal. Calcd. for C H N O •H O: C, 70.06; H, 6.03; N, 4.08.
3
2
40 40
2
8
2
chromatography to separate the intermediate product as diphthal-
imide which was then treated with hydrazine monohydrate and
Found: C, 69.98; H, 6.23; N, 3.92.
Synthesis of Crownophane 1.
EtOH at room temperature overnight to obtain the expected
1
After tandem Claisen rearrangement, macrocycle 7 was con-
verted to target crownophane 1 using NMP as solvent at 160 ºC
for 3.5 hours under Argon atmosphere. The solvent (NMP) was
removed under reduced pressure. The residue was subjected to
diamine with high yield (80%). H NMR: δ 1.71 (NH , 4H, s),
2
2.80~2.84 (O-CH -CH -NH , 4H, m), _3.54~3.59 (O-CH -CH -
2
2
2
2
2
NH , 4H, m), 3.85~3.90 (O-CH -CH -O, 4H, m), 4.2~4.3 (Ar-O-
2
2
2
CH -CH -O, 4H, m), 4.88(__=C-CH -O_ 4H, s),_ 5.51(=C-CH ,
2
2
2
2
2H, s), 7.19 (Ar-H, 4H_, s), 7.30~7.35 (Ar-H, 4H, m), 7.57~7.70
(Ar-H, 4H, m).
column chromatography on silica gel using AcOEt:CHCl (1:1)
3
as an eluent. Compound 1 was obtained as the main product.
1
Colorless crystal; yield 51%, R = 0.17; m.p. 221-222 ºC; H
f
Synthesis of Compound 10.
NMR: δ 3.6~3.7 (CH -CH -O, 12H, m), 3.69 (=C-CH -Ar, 4H,
2
2
2
Isophthaloyl dichloride and 2-(2-aminoethoxy)ethanol 8 were
s), 4.37~4.40 (Ar-O-CH -CH , 4H, m), 4.55 (C=CH , 2H, s),
2
2
2
treated with Et N as base in THF at room temperature for 1-2
7.06 (OH, 2H, s), 7.2~7.3 (Ar-H, 8H, m), 7.55~7.63 (Ar-H, 4H,
m), 8.00 (Py-H, 1H, t, 8Hz), 8.37 (Py-H, 2H, d, 8Hz), 8.55 (NH,
3
hours to obtain compound 9 and it was then converted to com-
1
13
pound 10 after tosylation [22]. H NMR: δ 2.42(Ar-CH , 6H, s),
2H, broad); C NMR: δ 31.58, 68.40, 70.68, 71.42, 110.82,
3
3.60~3.61(CH , 8H, m), 3.68~3.70 (CH , 4H, m), 4.19~4.22
112.28, 118.20, 123.58, 124.79, 125.08, 127.27, 128.77, 130.21,
2
2
-
(CH , 4H, m), 6.91(NH, 2H, s), 7.32 (Ar-H, 4H, d, 8Hz),
138.66, 145.49, 145.63, 146.12, 148.98, 164.32; IR (KBr, ν/cm
2
1
7.54(Ar-H, 1H, t, 8Hz), 7.75 (Ar-H, 4H, d, 8Hz), 8.03 (Ar-H, 2H,
d, 8Hz), 8.15(Ar-H, 1H, s).
): 1665, 1541, 1448, 1266, 1070. ESI-Mass: Calcd. for
+
+
C H N O , [M + Na ]: 700.27. Found: [M + Na ]: 700.4.
39 39
3 8
Anal. Calcd. for C H N O •H O: C,67.34; H, 5.90; N, 6.04.
39 39
3
8
2
Found: C, 67.26; H, 5.63; N, 6.07.
REFERENCES AND NOTES
Synthesis of Crownophane 2.
[1] S. Inokuma, S. Sakai and J. Nishimura, Top. Curr. Chem. 87,
172 (1994), and references cited therin.
Procedure is the same as that described for the preparation of
crownophane 1. Pale yellow crystal; yield 61%; R = 0.08; m.p.
[2a] R. M. Izatt, K. Pawlak and J. S. Bradshaw, Chem. Rev. 91,
1721 (1991); [b] R. M. Izatt. J. S. Bradshaw, K. Pawlak, R. L. Bruening
and B. J. Tarbet: Chem. Rev. 92, 1261 (1992).
[3] F. Diederich, "Cyclophanes", ed. By J.F. Stoddart:
Monographs in Supramolecular Chemistry. 1991, The Royal Society of
Chemistry, Cambridge.
[4a] C. D. Gutsche, "Calixarenes", ed. By J. F. Stoddart:
Monoghaphs in Supramolecular Chemistry. 1989, The Royal Society of
Chemistry, Cambridge; [b] "Calixarenes: a versatile Class of
Macrocyclic Compounds", ed. By J. Vincens, V. Bomer: Topics in
Inclusion Science, ed. By J.E.D. Davides: 1990, Kluwer Academic
Publishers, dordrecht.
f
1
110-111 ºC; H NMR: δ 3.6~3.7 (-O-CH CH -O, 8H, m), 3.69
2
2
(=C-CH -Ar, 4H, s), 3.81~3.84 (Ar-O-CH -CH , 4H, m),
2
2
2
4.36~4.40 (Ar-O-CH -CH , 4H, m), 4.41 (C=CH , 2H, s), 6.89
2
2
2
(NH, 2H, broad), 6.90 (OH, 2H, s), 7.16~7.30 (Ar-H, 4H, m),
7.19 (Ar-H, 2H, s), 7.32 (Ar-H, 1H, t, 6Hz), 7.54 (Ar-H, 2H, d,
8Hz), 7.69 (Ar-H, 2H, d, 8Hz), 7.76 (Ar-H, 2H, d, 6Hz), 8.35
13
(Ar-H, 1H, s); C NMR δ 31.87, 68.74,69.83, 69.94, 109.43,
110.77, 117.93, 123.57, 124.50, 126.53, 127.15, 128.71, 128.91,
129.48, 129.78, 134.79, 144.70, 145.61, 145.96, 167.21; IR (KBr,
-1
ν/cm ): 1647, 1537, 1475, 1449, 1283, 1070. ESI-Mass: Calcd.

582
S. Naher, K. Hiratani, M. Karikomi, and K. Haga
Vol. 42
[5] D. J. Cram: Angew. Chem. Int. Ed. Engl., 25, 1039 (1986).
[14a] F. Voegtle, W. M. Muller and W. H. Watson, Top. Curr. Chem.
125, 131 (1984); [b] J. A. A. de Boer, D. N. Reinhoudt, S. Harkema, G. J.
van Hummel and F. de Jong, J. Am. Chem. Soc., 104, 4073 (1982); [c] C.
J. van Staveren, V. M. L. J. Arts, P. D. J. Grootenhuis, J. van Eerden, S.
Harkema and D. N. Reinhoudt, J. Am. Chem. Soc., 108, 5271 (1986); [d]
P. D. J. Gtootenhuis, J. van Eerden, P. J. Dijkstra, S. Harkema and D. N.
Reinhoudt, J. Am. Chem. Soc. 109, 8044 (1987); [e] S. Harkema, G. J.
van Hummel, K. Daasvatn and D. N. Reinhoudt, J. Chem. Soc. Chem.
Commun., 368 (1981).
[15] K. Hiratani, T. Takahashi, K. Kasuga, H. Sugihara, K.
Fujiwara and K. Ohashi, Tetrahedron Lett., 36, 5567 (1995).
[16] K. Hiratani, K. Kasuga, M. Goto and H. Uzawa, J. Am. Chem.
Soc., 119, 12677 (1997).
[6a] T. Kaneda, S. Umeda, Y. Ishizaki, H. S. Kuo, S. Misumi, N.
Kanehisa ad N. Kasai: J. Am. Chem. Soc. 111, 1881 (1998); [b] T.
Kaneda, K. Hirose and S. Misumi, ibid, 111, 742 (1989).
[7a] K. Koenig, G. M. Lein, P. Stuckler, T. Kaneda and D. J. Cram:
J. Am. Chem. Soc. 101, 3535 (1979); [b] R. C. Helson, T. L. Tarnowski
and D. J. Dram, J. Org. Chem. 44, 2538 (1979); [c] G. M. Lein and D. J.
Cram, J. Am. Chem. Soc. 107, 448 (1985).
[8a] Y. Sun, A. E. Martell and R. Motekaitis, J. Inorg. Chem. 25,
4780 (1986); [b] A.R. van Doorn, M. Bos, S. Harkema, J. Van Eerden, W.
Verbon and D. N. Reinhoudt, J. Org. Chem: 56, 2371 (1991); [c] A. R.
van Dorn, R. Schaafstra, M. Bos, S. Harkema, J. van Eerden, W. Verbom
and D. N. Reinhoudt, ibid, 56, 6083 (1991).
[9] J.-M. Lehn, Supramolecular Chemistry, Concepts and
Perspectives, VHC, Weinheim, 1995.
[17] H. Uzawa, K. Hiratani, N. Minoura and T. Takahashi, Chem.
Lett., 307 (1998).
[10] C. J. Pedersen, J. Am. Chem. Soc. 89, 7017 (1967).
[11] F. de Jong and D. N. Reinhoudt: Adv. Phys. Org. Chem. 17,
279 (1980).
[12a] D. J. Cram and J. M. Cram, Acc. Chem. Res. 11, 8 (1978); [b]
J. M. Lehn, Science (Washington, D.C.) 227, 849 (1985); [c] H. M.
Colquhoun, J. F. Stoddart and D. Williams: J. Angew. Chem.Int. Ed.
Engl., 25, 487 (1986).
[18] K. Hiratani, T. Uzawa, K. Kasuga and H. Kobayashi,
Tetrahedron Lett., 38, 8993 (1997).
[19] H. Houjou, S. K. Lee, Y. Hishikawa, Y. Nagawa and K.
Hiratani, Chem. Commun., 2197 (2000).
[20] S. Tsuzuki, H. Houjou, Y. Nagawa, M. Goto and K. Hiratani,
J. Am. Chem. Soc., 123, 4255 (2001).
[21] C. J. Pedersen J. Org. Chem., 36, 1690 (1971).
[13] D. A. Hamilton and K. -H. Choi, J. Am. Chem. Soc. 123, 2456
(2001).
[22] M. Ouchi, Y. Inoue, Y. Liu, S. Nagamune, S. Nakamura, K.
Wada and K. Hakushi, Bull. Chem. Soc. Jpn., 63, 1260 (1990).