Synthesis and properties of bowl-shaped homotriazacalix[3 and 6] arenes and the acyclic analogues

Article abstract of DOI:10.1002/jhet.5570400110

Bowl-shaped chiral homotriazacalixarenes were prepared by the cyclization reactions of chiral triamines with three equimolar amounts of bis(chloromethyl) phenols or bis(chloromethyl) phenol-formaldehyde dimers in moderate yields. The corresponding acyclic

Full text of DOI:10.1002/jhet.5570400110

Jan-Feb 2003
Synthesis and Properties of Bowl-Shaped Homotriazacalix[3 and 6]
arenes and the Acyclic Analogues
77
Kazuaki Ito*, Tomokazu Sato and Yoshihiro Ohba
Department of Chemistry and Chemical Engineering, Faculty of Engineering,
Yamagata University, Yonezawa 992-8510, Japan.
Received June 3, 2002
Bowl-shaped chiral homotriazacalixarenes were prepared by the cyclization reactions of chiral triamines
with three equimolar amounts of bis(chloromethyl) phenols or bis(chloromethyl) phenol-formaldehyde
dimers in moderate yields. The corresponding acyclic phenol-formaldehyde oligomers were also synthe-
sized. The structural analysis of the macrocycles by nmr and circular dichroism spectra imply the existence
of chiral transmission from the point chirality of the cysteine bridge to the cyclophane moiety. Their cyclic
and acyclic compounds have a π-base cavity large enough to include the ammonium ion.
J. Heterocyclic Chem., 40, 77 (2003).
Introduction.
carbonate in 75 % (4a) and 97 % (4b) yields, respectively.
Treatment of 5a with three equimolar amount of
bis(chloromethyl) phenols (6a and 6b) or bis(chloro-
methyl)phenol-formaldehyde dimer 6c afforded macro-
cycles (1a, 1b, and 1c) in 14, 13, and 6 % yields, respec-
tively (Scheme 1). Analogous reactions using 4b with 6a
and 6c also gave the corresponding macrocycles (1d and
1e) in 5 and 15 % yields, respectively. However, the same
reactions of 4 with 6d, 6e, or 6f did not give any product
except polymeric materials. Corresponding acyclic com-
pounds 2 were prepared from the condensation reaction
between 4 and 7 in refluxing benzene, followed by reduc-
tion using sodium borohydride, in moderate yields
(Scheme 2 and 3).
Calixarenes are well known for their unique molecular
architecture, which is extensively used in the supramolec-
ular chemistry to build up more complex synthetic recep-
tors for ion and neutral molecules [1]. Despite such
progress of the calixarene chemistry, little effort has been
directed towards the methylene bridge [2]. This situation
inspired us to exploit the synthesis of calixarene analogs,
which were modified on the methylene moiety to other
unit. Introduction of other unit into the cyclic array easily
affect the entire molecules, thus providing the possibility
for other properties effectively. Therefore, we report syn-
theses of bowl-shaped homoazacalixarenes in which three
methylene bridges (-CH -) were replaced by three diho-
moaza bridges (-CH NRCH -), their structural detail
based on their nmr and circular dichroism spectra, and
their complexation toward ammonium ion. We also pre-
pared the corresponding acyclic compounds to compare
with the properties of the cyclic compounds.
2
The structure of macrocycles 1 and acyclic compounds 2
was determined on the bases of their elemental analysis and
spectral data, especially nmr spectra. The phenolic OH pro-
2
2
1
tons in H nmr spectra were observed at the range of δ 8.73-
11.20 ppm, indicating the existence of intramolecular
hydrogen bonding [3]. The ir spectral absorption band cor-
responding to OH stretching of the phenol unit was
Results and Discussion.
-1
observed at 3100-3300 cm , indicating the formation of
Chiral triamines 5 bearing three cysteine residues were
synthesized by the reactions of 1,3,5-tris(bromomethyl)-
benzenes 4a and 4b with cysteine methyl ester 3 in N,N-
dimethyl formaldehyde at 30 °C in the presence of sodium
strong intramolecular hydrogen bonding (Table 1)[3]. The
1
13
H and C nmr spectra of 1 showed C symmetry signal
3
pattern [4]. The ArCH N and ArCH Ar methylene protons
2
2

78
K. Ito, T. Sato and Y. Ohba
Vol. 40
Scheme 2
Scheme 3
of 1 appeared as two (for 1a, 1b, and 1d) or three (for 1c and
1e) pair of doublets due to the geminal coupling between
ArCH Ar methylene protons of calixarenes is generally ca.
2
0.9±0.2 ppm for syn orientation of the aryl rings and zero for
anti [5]. Applying this rule to 1c and 1e, the ∆δ values (1.00
ppm for 1c and 0.98 ppm for 1e) indicate that the phenol-
formaldehyde dimer moiety adopts a syn orientation. This is
further supported by the chemical shift values of the
H
and H
protons at room temperature (Table 2).
exo
endo
These pairs did not coalesce at 55 °C in deuteriochloroform,
indicating that 1 exists as a rigid structure. Conformational
analysis of the phenol-formaldehyde dimer moiety in 1c and
1e was carried out by using nmr spectroscopy. The
ArCH Ar methylene carbon atoms (δ 30.9 ppm for 1c and δ
2
ArCH Ar methylene region is informative and diagnostic
30.8 ppm for 1e) [6]. Based on these results, the cone-like
form may adopt a preferable conformation in 1.
2
for conformational assignments. The ArCH Ar methylene
2
protons of 1c and 1e were observed as AB systems. It is
The different ∆δ values of the ArCH N methylene pro-
2
known that the ∆δ values between H and H
of the
tons (∆δH H and ∆δH H ) imply that the cyclophane
exo
endo
f
g
n o

Jan-Feb 2003
Synthesis and Properties of Bowl-Shaped Homotriazacalix[3 and 6] arenes
79
the dihedral angle between the methylene protons and the
plane of the adjacent aromatic rings as shown in Figure 1.
Since the smaller ∆δ values are ascribed to the H H meth-
f
g
ylene protons, it is reasonable to assume that the phenol
ring adjacent to the H H methylene moiety adopt a con-
f
g
formation A in Figure 1. The CPK model consideration
also supports the fact that the phenol rings somewhat flat-
ten owing to steric repulsion between the hydroxyl group
of the phenol ring and methyl ester group of the cysteine
moiety. Therefore, it is reasonable to assume that the direc-
tion of the intramolecular hydrogen bonding of 1 is
effected by the point chirality of the cysteine unit. In this
case, the chirality of the L-cysteine bridge cause the
predominate formation of the left-hand isomer in Figure 2.
In other words, the point chirality of the cysteine unit
transfers to the cyclophane moiety. To prove the existence
of the chiral cyclophane moiety, circular dichroism spec-
tral measurement was employed. The circular dichroism
spectral absorptions were observed at ca. 295 nm, which
were corresponding to the phenol unit (Figure 3 and Table
3)[7]. Therefore, circular dichroism spectra supported the
assumption that the cyclophane unit is chiral. In contrast,
circular dichroism spectral absorptions of acyclic com-
pounds 2 were fairly small.
moiety is twisted. The ∆δ values of the methylene protons
of the cyclophane moiety are expected to be sensitive to

80
K. Ito, T. Sato and Y. Ohba
Vol. 40
resonances of 8 moved to a high field due to the ring cur-
rent effect of the π-cavity of 1e during the formation of the
complex 1e-8 (Table 4). The highest induced shifts of
+
methyl protons of N (CH ) of 8 suggest that the cation
3 3
moiety is included in the aromatic π-cavity of 1e. However
chiral selectivity with 1e was not observed [9]. In the same
experiment using 1a, homoazacalix[3]arene, however, the
chemical shift of 8 scarcely changes due to the small
π-cavity of 1a. Interestingly, the methyl signals of
+
N (CH ) of 8 in the presence of the corresponding acyclic
3 3
compounds (2a and 2d) shifted to a high field. Compound
2 may show behavior consistent with the induce-fit model
when encapsulating the ammonium ion 8.
In summary, we prepared the bowl-shaped chiral homo-
triazacalixarenes and the corresponding acyclic com-
pounds in moderate yields. Their nmr and circular
dichloroism spectra of macrocycles imply the existence of
the chiral transmission from the point chirality of the
bridge to the molecule as a whole. Their cyclic and acyclic
compounds contain a π-base cavity large enough to
include ammonium ion.
Figure 3. Circular Dichroism Spectra of 1 in chloroform at 20 °C.
It is known that the cyclophanes form complexes with
ammonium ions [8]. Therefore, we examined the complex-
ation ability of these macrocycles 1 and the corresponding
acyclic oligomers 2 with racemic α -methyl benzyl
1
trimethyl ammonium iodide 8 using H nmr spectroscopy.
In the presence of 1e, homoazacalix[6]arene, all proton

Jan-Feb 2003
Synthesis and Properties of Bowl-Shaped Homotriazacalix[3 and 6] arenes
81
EXPERIMENTAL
General Procedure for the Preparation of Homotriaza-
calixarenes (1).
1D and 2D nmr measurements were performed on Varian
Mercury 200 and INOVA 500 spectrophotometers in solvents as
indicated. Chemical shifts are reported as part per militon (δ) rel-
ative to tetramethylsilane. Melting points were obtained on
Yanagimoto micro melting point apparatus and are uncorrected.
Ir and uv spectra were recorded on Horiba FT-200 and Hitachi
228A spectrophotometers, respectively. Fab-mass spectra were
obtained on a JEOL AX-505 HA spectrometer using m-
nitorobenzyl alcohol as a matrix. Circular dichroism spectra were
collected by Jasco J720WI spectrophotometer. All commercially
available compounds were used without further purification
unless otherwise indicated. Column chromatography was per-
formed on Merck Silica (kieselgel 60, 63-200 mm, 70-230 mesh).
1,3,5-Tris(bromomethyl)benzene (4a) [10] and 1,3,5-tris- (bro-
momethyl)-2,4,6-triethylbenzene (4b) [11], bis(chloromethyl)-p-
substituted phenols (6a, 6b) [12] and bis(chloromethyl)-p-substi-
tuted phenol-formaldehyde oligomers (6c-6f) [13,14], and 2-
hydroxyl-5-methyl benzaldhyde (7a) [15] and 2-hydroxyl-3-(2-
hydroxyl-5-methylphenyl)methyl-5-methylbenzaldehyde (7b)
[15] were prepared according to the literature.
To a suspension of sodium carbonate (318 mg, 2.0 mmol) in
N,N-dimethyl formaldehyde (10 ml) were added a solution of 5
(173 mg, 0.33 mmol) in N,N-dimethyl formaldehyde (30 ml) and
a solution of 6 ( mmol) in N,N-dimethyl formaldehyde (30 ml)
simultaneously at 30 °C over 2 h. After the addition was com-
plete, the mixture was allowed to stir at 30 °C for 5 h. Removal of
N,N-dimethyl formaldehyde under a reduced pressure below 40
°C gave an yellow oily residue, which was subjected to column
chromatography on silica gel using hexane:ethyl acetate 2:3 as an
eluent to give 1 as colorless crystals.
1
Compound 1a was obtained in 14 % yield. Mp 270-273 °C. H
nmr (deuteriochloroform): δ 2.13 (s, 9H, CH x 3), 2.79 (d, 3H,
3
J=10.0 Hz, H x 3), 3.11 (d, 3H, J=12.0 Hz, H x 3), 3.21 (dd, 3H,
c
o
J=10.0, 12.0 Hz, H x 3), 3.47 (d, 3H, J=12.0 Hz, H x 3), 3.55
d
e
(d, 3H, J=15.5 Hz, H x 3), 3.63 (d, 3H, J=14.0 Hz, H x 3), 3.74
g
b
(d, 3H, J=14.0 Hz, H x 3), 3.82 (s, 9H, CO CH x 3), 3.86 (d,
a
2
3
3H, J=15.5 Hz, H x 3), 4.24 (s, 3H, J=13.0 Hz, H x 3), 6.60 (s,
f
n
3H, H x 3), 6.74 (s, 3H, H x 3), 7.16 (s, 3H, Ar-H x 3), 10.60 (s,
h
i
13
3H, OH x 3). C nmr (deuteriochloroform): δ 20.3, 31.5, 37.2,
51.6, 51.8, 53.5, 59.7, 120.1, 122.3, 127.2, 128.3, 129.4, 130.5,
-
138.8, 153.0, 170.3. Ir (chloroform): 3089 (ν ), 1732 (ν ) cm
. Fab-mass 917 (M+H) .
Synthesis of Amine Derivatives (5).
OH
CO
1
+
A mixture of L-cysteine methyl ester monohydrochloride 3
(1.54 g, 9.0 mmol), sodium carbonate (4.4 g, 41 mmol), and N,N-
dimethyl formaldehyde (20 ml) was added to a solution of 4 (2.0
mmol) in N,N-dimethyl formaldehyde (20 ml) over 0.5 h at room
temperature. After the addition was completed, the mixture was
allowed to stir at room temperature for 4 h. Removal of N,N-
dimethyl formaldehyde under a reduced pressure gave yellow
oily residue, which was dissolved with chloroform. The solution
Anal. Calcd. for C H N O S : C, 62.93; H, 6.27; N, 4.59.
48 57
3 9 3
Found C, 63.10; H, 6.10; N, 4.55.
Compound 1b was obtained in 13 % yield. Mp 155-157 °C. H
nmr (deuteriochlorofrom): δ 1.19 (s, 27H, t-Bu x 3), 2.83 (d, 3H,
1
J=8.5 Hz, H x 3), 3.16 (d, 3H, J=13.5 Hz, H x 3), 3.22 (dd, 3H,
c
o
J=8.5, 11.0 Hz, H x 3), 3.52 (d, 3H, J=11.0 Hz, H x 3), 3.61 (d,
d
e
3H, J=15.5 Hz, H x 3), 3.64 (d, 3H, J=14.5 Hz, H x 3), 3.75 (d,
g
b
3H, J=14.5 Hz, H x 3), 3.84 (s, 9H, CO CH x 3), 3.88 (d, 3H,
a
2
3
was washed with water, 5% NaHCO aqueous solution, and
3
J=15.5 Hz, H x 3), 4.28 (d, 3H, J=13.5 Hz, H x 3), 6.79 (s, 3H,
f
n
water again. The organic layer was dried over anhydrous sodium
sulfate. Removal of solvent gave 5 as a colorless oil.
H x 3), 6.91 (s, 3H, H x 3), 7.17 (s 3H, Ar-H x 3), 10.60 (s, 3H,
h
i
13
OH x 3). C nmr (deuteriochlorofrom): δ 31.4, 31.5, 33.8, 37.2,
2-Amino-3-[3,5-bis-(2-amino-2-methoxycarbonylethylsulfanyl-
51.6, 52.2, 53.8, 59.8, 119.7, 121.9, 125.6, 126.8, 128.3, 138.8,
methyl)benzylsulfanyl]propionic Acid Methyl Ester (5a).
140.8, 153.0, 170.5. Ir (chloroform): 3111 (ν ), 1732 (ν
cm . Fab-mass 1043 (M+H) .
)
OH
CO
-1
+
1
The yield was 75 %. Colorless oil. H nmr (deuteriochloro-
Anal. Calcd. for C H N O S : C, 65.68; H, 7.25; N, 4.03.
57 75
3 9 3
form): δ 2.67 (dd, 3H, J=7.2, 13.5 Hz, CH x 3), 2.83 (dd, 3H,
J=4.8, 13.5 Hz, CH x 3), 3.61 (dd, 3H, J=4.8, 7.2 Hz, CH x 3),
Found C, 65.70; H, 7.30; N, 3.89.
Compound 1c was obtained in 6 % yield. Mp 245-248 °C. H
nmr (deuteriochloroform): δ 2.10 (s, 9H, CH x 3), 2.21 (s, 9H,
1
3.72 (s, 6H, CH x 3), 3.74 (s, 9H, CO CH x 3), 7.17 (s, 3H, Ar-
2
2
3
13
H x 3). C nmr (deuteriochloroform): δ 36.4, 36.5, 52.2, 54.0,
128.3, 138.7, 174.3. Ir (oil): 1732 (ν ) cm . Fab-mass 520
3
-1
CH x 3), 2.55 (d, 3H, J=14.0 Hz, H x 3), 2.84 (d, 3H, J=12.0
3
c
CO
+
Hz, H x 3), 3.00 (dd, 3H, J=12.0, 14.0 Hz, H x 3), 3.30 (s, 3H,
(M+H) .
o
d
J=14.0 Hz, H x 3), 3.34 (d, 3H, J=14.5 Hz, H x 3), 3.47 (s, 3H,
Anal. Calcd. for C H N O S : C, 48.53; H, 6.40; N, 8.09.
k
g
21 33
3 6 3
J=12.5 Hz, H x 3), 3.58 (d, 3H, J=12.5 Hz, H x 3), 3.69 (d, 3H,
Found: C, 48.30; H, 6.60; N, 7.98.
a
e
J=13.0 Hz, H x 3), 3.90 (d, 3H, J=14.0 Hz, H x 3), 3.90 (s, 9H,
b
f
Amino-3-[3,5-bis-(2-amino-2-methoxycarbonylethylsulfanyl-
methyl)-2,4,6-triethylbenzylsulfanyl]propionic Acid Methyl
Ester (5b).
CO CH x 3), 4.30 (d, 3H, J=13.5 Hz, H x 3), 4.69 (d, 3H,
2
3
j
J=12.0 Hz, H x 3), 6.61 (s, 3H, H x 3), 6.74 (s, 3H, H x 3),
n
h
m
6.97 (s, 3H, H x 3), 7.01 (s, 3H, H x 3), 7.38 (s, 3H, Ar-H x 3),
i
l
13
1
8.76 (s, 3H, OH x 3), 11.20 (s, 3H, OH x 3). C nmr (deuterio-
chloroform): δ 20.3, 20.5, 25.1, 30.9, 36.1, 51.4, 51.5, 53.4, 63.4,
121.4, 122.9, 127.6, 128.2, 128.3, 128.4, 128.9, 129.4, 129.5,
131.3, 131.9, 139.7, 149.5, 150.9, 170.6. Ir (chloroform): 3288
The yield was 97 %. Colorless oil. H nmr (deuteriochloro-
form): δ 1.29 (t, 9H, J=7.0 Hz, CH CH x 3), 2.89 (q, 6H, J=7.0
2
3
Hz, CH CH x 3), 2.89 (dd, 3H, J=7.0, 13.5 Hz, CH x 3), 3.00
2
3
(dd, 3H, J=5.0, 13.5 Hz, CH x 3), 3.71 (dd, 3H, J=5.0, 7.0 Hz,
-1
+
13
(ν ), 1726 (ν ) cm . Fab-mass 1276 (M+H) .
CH x 3), 3.77 (s, 9H, CO CH x 3), 3.79 (s, 6H, CH x 3).
C
OH
CO
2
3
2
Anal. Calcd. for C H N O S : C, 67.74; H, 6.40; N, 3.29.
nmr (deuteriochloroform): δ 16.2, 22.9, 31.9, 38.7, 52.2, 54.3,
72 81
3 12 3
-1
131.2, 142.6, 174.5. Ir (oil): 1739 (ν ) cm . Fab-mass: 604
C, 67.80; H, 6.30; N, 3.36.
Compound 1d was obtained in 5 % yield. Mp 178-181 °C. H
nmr (deuteriochloroform): δ 1.12 (t, 9H, J=7.5 Hz, CH CH x 3),
CO
+
1
(M+H) .
Anal. Calcd. for C H N O S : C, 53.70; H, 7.51; N, 6.96.
27 45
3 6 3
2
3
Found: 53.50; H, 7.20; N, 6.70.
2.14 (s, 9H, CH x 3), 2.76-2.80 (m, 9H, CH CH x 2 and H x
3
2
3
c

82
K. Ito, T. Sato and Y. Ohba
Vol. 40
3), 3.18 (d, 3H, J=13.0 Hz, H x 3), 3.29 (dd, 3H, J=7.5, 14.5 Hz,
(s, 9H, CO CH x 3), 3.78 (d, 3H, J=14.0 Hz, H x 3), 3.84 (d,
2 3 j
o
H x 3), 3.44-3.53 (m, 9H, H , H , and H ), 3.82 (s, 9H, CO CH
3H, J=14.0 Hz, H x 3), 3.89 (d, 3H, J=14.0 Hz, H x 3), 6.57 (d,
d
g
b
e
2
3
k
g
x 3), 3.86 (d, 3H, J=14.5 Hz, H x 3), 4.19 (d, 3H, J=13.5 Hz, H
3H, J=2.0 Hz, H x 3), 6.74 (d, 3H, J=8.0 Hz, H x 3), 6.85 (dd,
h n
a
f
3H, J=2.0, 8.0 Hz, H x 3), 7.00 (d, 3H, J=2.0 Hz, H x 3), 7.02
x 3), 4.22 (d, 3H, J=12.0 Hz, H x 3), 6.60 (s, 3H, H x 3), 6.75
m
l
n
h
13
13
(d, 3H, J=2.0 Hz, H x 3), 7.17 (s, 3H, Ar-H x 3). C nmr (deu-
(s, 3H, H x 3), 10.5 (s, 3H, OH x 3). C nmr (deuteriochloro-
i
i
teriochloroform): δ 20.4, 20.5, 30.8, 34.0, 36.4, 50.6, 52.5, 59.0,
116.7, 121.3, 127.1, 127.6, 127.8, 128.4, 128.5, 129.3, 129.4,
130.5, 130.9, 138.7, 151.0, 152.0, 172.3. Ir (chloroform): 3319
form): δ 15.3, 20.3, 29.1, 29.8, 51.5, 53.2, 60.1, 120.1, 122.3,
127.0, 129.5, 130.6, 131.1, 142.7, 153.0, 170.6. Ir (chloroform):
-1
+
3107 (ν ), 1732 (ν ) cm . Fab-mass 999 (M+H) .
OH
CO
-1
+
(ν ), 1732 (ν ) cm . Fab-mass 1240 (M+H) .
Anal. Calcd. for C H N O S : C, 64.86; H, 6.91; N, 4.20. C,
OH
CO
54 69
3 9 3
Anal. Calcd. for C H N O S : C, 66.83; H, 6.54; N, 3.39.
64.78; H, 6.80; N, 4.10.
Compound 1e was obtained in 15 % yield. Mp 273-276 °C. H
nmr (deuteriochloroform): δ 1.07 (t, 9H, J=7.5 Hz, -CH CH x
69 81
3 12 3
1
Found C, 66.60; H, 6.60; N, 3.50.
Compound 2c was obtained in 22 % yield. Mp 69-78 °C. H
nmr (deuteriochloroform): δ 1.20-1.27 (m, 9H, CH CH x 3),
1
2
3
3), 2.17 (s, 9H, CH x 3), 2.21 (s, 9H, CH x 3), 2.52 (d, 3H,
3
3
2
3
J=13.5 Hz, H x 3), 2.96 (dd, 3H, J=13.0, 13.5 Hz, H x 3), 3.02
2.23 (s, 9H, CH x 3), 2.81-2.96 (m, 12H, CH CH x 3, H x 3
c
d
3 2 3 c
(d, 3H, J=12.0 Hz, H x 3), 3.08 (m, 3H, -CHHCH x 3), 3.14 (d,
and H x 3), 3.53 (dd, 3H, J=5.5, 6.5 Hz, H x 3), 3.77 (d, 3H,
d e
n
3
3H, J=14.5 Hz, H x 3), 3.27 (d, 3H, J=14.0 Hz, H x 3), 3.33 (d,
J=13.5 Hz, H x 3), 3.78 (s, 9H, CO CH x 3), 4.00 (d, 3H,
a
j
f 2 3
3H, J=14.0 Hz, H x 3), 3.53 (m, 6H, He x 3 and CHHCH x 3),
J=13.5 Hz, H x 3), 6.76 (d, 3H, J=8.0 Hz, H x 3), 6.78 (d, 3H,
g n
f
3
13
3.82 (d, 3H, J=14.5 Hz, H x 3), 3.84 (s, 9H, CO CH x 3), 4.13
J=2.0 Hz, H x 3), 6.97 (dd, 3H, J=2.0, 8.0 Hz, H x 3). C nmr
b
2
3
l
m
(d, 3H, J=14.0 Hz, H x 3), 4.25 (d, 3H, J=14.0 Hz, H x 3), 4.48
(deuteriochloroform): δ 16.2, 20.4, 23.0, 31.9, 36.3, 50.9, 52.4,
g
k
(d, 3H, J=12.0 Hz, H x 3), 6.57 (s, 3H, H x 3), 6.76 (s, 3H, H
59.3, 116.4, 121.7, 128.4, 129.3, 129.5, 131.0, 142.8, 155.3,
o
h
m
-1
x 3), 6.97 (s, 3H, H x 3), 7.00 (s, 3H, H x 3), 8.73 (s, 3H, OH x
172.8. IR (CHCl ): 3313 (ν ), 1732 (ν ) cm . Fab-mass 964.
i
l
3
OH
CO
13
+
3), 11.12 (s, 3H, OH x 3). C nmr (deuteriochloroform): δ 16.4,
20.3, 20.5, 22.2, 25.3, 30.0, 30.8, 50.3, 51.1, 53.4, 62.7, 121.1,
123.1, 127.3, 128.2, 128.3, 128.4, 129.2, 129.4, 131.2, 131.7,
(M+H) .
Anal. Calcd. for C H N O S : C, 63.55; H, 7.17; N, 4.36.
51 69
3 9 3
Found C, 63.60; H, 7.30; N, 4.50.
Compound 2d was obtained in 44 % yield. mp 83-93 °C. H
nmr (deuteriochloroform): δ 1.23-1.26 (m, 9H, CH CH x 3),
1
132.7, 142.2, 149.6, 151.0, 169.8. Ir (chloroform) : 3288 (ν ),
OH
-1
+
1726 (ν ) cm . Fab-mass 1360 (M+H) .
CO
2
3
Anal. Calcd. for C H N O S : C, 68.85; H, 6.89; N, 3.09.
2.20 (s, 9H, CH x 3), 2.24 (s, 9H, CH x 3), 2.80-3.00 (m, 12H,
78 93
3 12 3
3
3
Found C, 69.10; H, 6.80; N, 3.20.
CH CH x 3, H x 3 and H x 3), 3.48 (dd, 3H, J=5.5, 6.0 Hz, H
2
3
c
d
e
x 3), 3.74 (d, 3H, J=13.5 Hz, H x 3), 3.75 (s, 9H, CO CH x 3),
f
2
3
Synthesis of Acyclic Compounds (2).
3.77 (s, 6H, H x 3 and H x 3), 3.79 (d, 3H, J=14.5 Hz, H x 3),
a
b
j
A mixture of 4 (1.3 mmol) and 7 (4.2 mmol) in dry benzene
(50 ml) was refluxed for 6 h. Removal of benzene gave yellow
oily residue, which was dissolved with methanol (70 ml) and
dichloromethane (30 ml). The solution was cooled to 0 °C in an
ice bath, and then sodium borohydride (11 mmol) was added
small portion over 0.5 h. After the addition was completed, the
mixture was allowed to stir at room temperature for 2 h. After
removing the solvent, the residue was dissolved with chloroform.
The solution was washed with water several times. The organic
layer was dried over anhydrous sodium sulfate. Condensation of
the solution gave yellow oily residue, which was subjected to col-
umn chromatography on silica gel using ethyl acetate: hexane 1:1
as an eluent to give 2 as pale yellow crystals.
3.84 (d, 3H, J=14.5 Hz, H x 3), 3.96 (d, 3H, J=13.5 Hz, H x 3),
k
g
6.62 (d, 3H, J=2.0 Hz, H x 3), 6.74 (d, 3H, J=8.0 Hz, H x 3),
h
n
6.87 (dd, 3H, J=2.0, 8.0 Hz, H x 3), 7.01 (d, 3H, J=2.0 Hz, H x
m
l
13
3), 7.03 (d, 3H, J=2.0 Hz, H x 3). C nmr (deuteriochloroform):
i
δ 16.2, 20.5 x 2, 23.0, 30.8, 31.8, 35.8, 50.6, 52.5, 58.9, 116.7,
121.1, 127.1, 127.7, 127.8, 128.4, 129.3, 129.5, 130.5, 130.8,
130.9, 142.9, 151.0, 152.0, 172.4. Ir (chloroform): 3319 (ν ),
OH
-1
+
1739 (ν ) cm . Fab-mass 1324 (M+H) .
CO
Anal Calcd for C H N O S : C, 68.03; H, 7.03; N, 3.17.
75 93
3 12 3
Found C, 67.89; H, 6.88; N, 3.30.
REFERENCES AND NOTES
1
Compound 2a was obtained in 34 % yield. Mp 65-69 °C. H
[1a] C. D. Gutsche Calixarene, Royal Society of Chemistry,
London (1989); [b] J. Vincens, V. Böhmer. Calixarenes: A Versatile
Calss of Macrocyclic Compounds, Kluwer Academic Publishers,
Dordecht (1991); [c] C. D. Gutsche, Calixarenes Revisted, Royal
Society of Chemistry, London (1998).
[2a] I. U. Khan, H. Takemura, M. Suenaga, T. Shinmyozu and
T. Inazu, J. Org. Chem., 58, 3158 (1993); [b] P. D. Hampton, W. Tong,
S. Wu and E. N. Duesler, J. Chem. Soc., Perkin Trans 2, 1127 (1996);
[c] K. Ito, Y. Ohba and T. Sone, Nippon Kagaku Kaishi, 217 (1999).
[3] page 100 in ref. 1a.
nmr (deuteriochloroform): δ 2.22 (s, 9H, CH x 3), 2.67 (dd, 3H,
3
J=7.0, 13.5 Hz, 3H, H x 3), 2.79 (dd, 3H, J=5.0, 13.5 Hz, H x
c
d
3), 3.43 (dd, 3H, J=5.0, 7.0 Hz, H x 3), 3.65 (s, 6H, H x 3 and
e
a
H x 3), 3.66 (d, 3H, J=13.5 Hz, H x 3), 3.75 (s, 9H, CO CH x
b
f
2
3
3), 3.94 (d, 3H, J=13.5 Hz, H x 3), 6.74 (d, 3H, J=1.5 Hz, H x
g
l
3), 6.75 (d, 3H, J=8.5 Hz, H x 3), 6.97 (dd, 3H, J=1.5, 8.0 Hz,
n
13
H
x 3), 7.13 (s, 3H, Ar-H x 3), 9.70 (s, 3H, OH x 3). C nmr
m
(deuteriochloroform): δ 20.4, 34.2, 36.3, 50.9, 52.4, 59.1, 116.3,
121.8, 128.3, 128.4, 129.2, 129.5, 138.6, 155.3, 172.9. Ir (chloro-
-1
+
form): 3313 (ν ), 1739 (ν ) cm . Fab-mass 880 (M+H) .
OH
CO
[4a] M. Takeshita, S. Nishio and S. Shinkai, J. Org. Chem., 59,
Anal. Calcd. for C H N O S : C, 61.43; H, 6.48; N, 4.78.
45 57
3 9 3
4032 (1994); [b]
K. Araki and H. Hayashida, Tetrahedron Lett.,
Found C, 61.54; H, 6.38; N, 4.90.
Compound 2b was obtained in 58 % yield. Mp 70-78 °C. H
41, 1807 (2000).
1
[5] page 110-111 in ref. 1a.
[6] C. Jaime, J. de Mendoza, P. Prados, P. M. Nieto and S.
Sanchez, J. Org. Chem., 56 3372 (1991).
nmr (deuteriochloroform): δ 2.18 (s, 9H, CH x 3), 2.23 (s, 9H,
3
CH x 3), 2.66 (dd, 3H, J=8.0, 14.0 Hz, H x 3), 2.78 (dd, 3H,
3
c
J=4.5, 14.0 Hz, H x 3), 3.36 (dd, 3H, J=4.5, 8.0 Hz, H x 3), 3.60
[7] T. Arimura, H. Kawabata, T. Matsuda, T. Muramatsu, H.
Satoh, K. Fujio, O. Manabe and S. Shinkai, J. Org. Chem., 56, 301
d
e
(d, 3H, J=14.0 Hz, H x 3), 3.64 (s, 6H, H x 3 and H x 3), 3.70
f
a
b

Jan-Feb 2003
Synthesis and Properties of Bowl-Shaped Homotriazacalix[3 and 6] arenes
83
(1991).
Int. Ed. Engl., 36, 862 (1997).
[8] K. Araki, H. Shimizu and S. Shinkai, Chem. Lett., 205
(1993).
[9] It is too small π-cavity of 1 to discriminate the enantiomer
of 8.
[10] W. P. Cochrane, P. L. Pauson and T. S. Stevens, J. Chem.
[12] K. Ito, Y. Ohba and T. Sone, Heterocycles, 51, 2203
(1999).
[13] K. Ito, T. Ohta, Y. Ohba and T. Sone, J. Heterocyclic
Chem., 37, 79 (2000).
[14] K. Ito, T. Nagai, Y. Ohba and T. Sone, J. Heterocyclic
Chem., 37, 1121 (2000).
Soc. (C), 630 (1968).
[11] A. Metzger, V. M. Lynch and E. V. Anslyn, Angew. Chem.
[15] H. Christensen, Synth. Commun., 5, 65 (1975).