Synthesis of novel calixarenes having a tweezer-type structure

Article abstract of DOI:10.1016/j.tetlet.2005.02.064

Monobromide was used as the starting material. The [2+2]photocycloaddition of diolefins directly gave all the calix[4]arene regioisomers having chiral and achiral structures in 20-47% yields. They formed a complex with alkali metal ions and extracted large metal picrates rather than small ones.

Full text of DOI:10.1016/j.tetlet.2005.02.064

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3261–3263
Synthesis of novel calixarenes having a tweezer-type structure
Yukihiro Okada,a,* Masashi Yoshidaa and Jun Nishimurab,*
aDepartment of Chemistry, Gunma University, Kiryu 376-8515, Japan
bDepartment of Nano-Material Systems, Gunma University, Kiryu 376-8515, Japan
Received 20 October 2004; revised 3 February 2005; accepted 4 February 2005
Available online 24 March 2005
Abstract—Monobromide was used as the starting material. The [2+2]photocycloaddition of diolefins directly gave all the calix[4]-
arene regioisomers having chiral and achiral structures in 20–47% yields. They formed a complex with alkali metal ions and
extracted large metal picrates rather than small ones.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Intramolecular [2+2]photocycloaddition of styrene
derivatives is a powerful and convenient method for
the construction of a calixarene-like skeleton (e.g., trans-
formation of diolefin 4 into macrocycle 5).1–3 The cyclo-
butane ring maintained the desired conformation of
calix[4]arene analogs to suppress the benzene ring rota-
tion at the opposite 1,3-position.4–6 Accordingly, two
bisphenol units were forced to adopt a face-to-face con-
formation, forming a cage structure such as calix[4]-
arene. Although many calix[n]arenes were reported as
powerful host molecules, the molecular tweezer-type
calixarenes, especially those of chiral structures, are
scarcely known.7–11 Therefore, we were prompted to de-
velop a direct synthesis of three regioisomers of this type
of calixarene by using the same starting material. In this
paper, we report a simple synthesis of tweezer-type ca-
lix[4]arenes by the intramolecular photocycloaddition.
for 18 h. The vinylation of 3 was performed with tributyl
vinyl tin, PdCl2(PPh3)2, and LiCl in dry DMF at 80 ꢁC
for 6 h to give diolefins 4 in 38–45% yields. [2+2]Photo-
cycloaddition of 4 (0.11–1.2 mM) was carried out by
irradiation with a 400 W high-pressure Hg lamp (pyrex
filter) in dry benzene for 23 h. After evaporation, calix-
[4]arenes 5 were isolated in 41–47% yields by column
chromatography (SiO2, benzene/ethyl acetate = 2/1).
Calixarenes 8 having a crown ether (n = 3–5) close to the
cyclobutane ring were obtained as follows: dibromides 6
were obtained in 73–88% yields by etherification with
2b, the corresponding oligoethyleneglycol ditosylate,
and K2CO3 in dry DMF at 100 ꢁC for 18 h. The vinyl-
ation of 6 was performed with tributyl vinyl tin,
PdCl2(PPh3)2, and LiCl in dry DMF at 80 ꢁC for 6 h
to give diolefins 7 in 44–50% yields. [2+2]Photocycload-
dition of 7 was carried out by irradiation with a 400 W
high-pressure Hg lamp (pyrex filter) in dry benzene for
23 h. After evaporation, calix[4]arenes 8 were isolated
in 20–46% yields by column chromatography (SiO2,
benzene/ethyl acetate = 2/1).
The synthesis of all calix[4]arene analogs is shown in
Scheme 1. Monobromide 1 was used as the starting
material. Monoetherification of 1 was performed with
Li2CO3 and CH3I in dry DMF at rt for 12 h to give
monomethylether 2a and b in 68 and 17% yields, respec-
tively. Calixarenes 5 having a crown ether (n = 3–5)
apart from the cyclobutane ring were obtained as fol-
lows: dibromides 3 were obtained in 84–92% yields by
the etherification with 2a, the corresponding oligoethyl-
eneglycol ditosylate, and K2CO3 in dry DMF at 100 ꢁC
Chiral calixarenes 13 were obtained as follows: mono-
bromides 9 were obtained in quantitative yields by
etherification with 2b, the corresponding oligoethylene-
glycol monotosylate, and K2CO3 in dry DMF at 80–
90 ꢁC for 18 h. The tosylation of 9 was performed with
TsCl, triethylamine, 4-(dimethylamino)pyridine in dry
CH2Cl2 for 24 h to give tosylates 10 in quantitative
yields. Dibromides 11 were obtained in 79–83% yields
by etherification with 2a, 10, and K2CO3 in dry DMF
at 80–90 ꢁC for 18 h. The vinylation of 11 was per-
formed with tributyl vinyl tin, PdCl2(PPh3)2, and LiCl
Keywords: Calixarene; Cyclophane; Photocycloaddition; Alkali metal
ion.
*
Corresponding authors. Tel./fax: +81 277 30 1311; e-mail: okada@
chem.gunma-u.ac.jp
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.02.064

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Y. Okada et al. / Tetrahedron Letters 46 (2005) 3261–3263
OH
OH
OCH3 OH
OH
OCH3
Br
Li2CO3
CH3I
DMF, r.t., 12 h
Br
Br
+
1
2b
2a
n-1O
(n-Bu)3SnCH=CH2
PdCl2(PPh3)2
n-1
OCH3 O
O
OCH3
Br
TsO
O
K2CO3
OTs
Br
2a
DMF, LiCl
80 ˚C, 6 h
DMF, 100 ˚C, 18 h
3
O
O
n-1
OCH3
OCH3
OCH3
O
O n-1
O
hν (Pyrex)
dry benzene
23 h
O
OCH3
n=3-5
4
5
n-1
(n-Bu)3SnCH=CH2
OCH3
PdCl2(PPh3)2
n-1
OCH3
O
OTs
O
O
TsO
O
K2CO3
Br Br
2b
DMF, LiCl
80 ˚C, 6 h
DMF, 100 ˚C, 18 h
6
O
O
n-1
OCH3
O n-1
OCH3
OCH3
O
O
hν (Pyrex)
O
OCH3
dry benzene
23 h
n=3-5
7
8
n-1
O
n-1OTs
OCH3
O
OCH3
O
O
n-1OH
TsO
OH
O
K2CO3
Br
TsCl, N(CH2CH3)3
Br
2b
DMF, 80-90 ˚C,
18 h
CH2Cl2,
N
N
9
10
n-1
O
2a
OCH3
O
O
OCH3
(n-Bu)3SnCH=CH2
PdCl2(PPh3)2
Br
Br
K2CO3
DMF, 80-90 ˚C,
18 h
DMF, LiCl
80 ˚C, 6 h
11
O
n-1
CH3O
O
O n-1
O
OCH3
OCH3
O
hν (Pyrex)
dry benzene
23 h
O
OCH3
13
12
n=3-5
Scheme 1.
in dry DMF at 80 ꢁC for 6 h to give diolefins 12 in 43–
52% yields. [2+2]Photocycloaddition of 12 was carried
out by irradiation with a 400 W high-pressure Hg lamp
(pyrex filter) in dry benzene for 23 h. After evaporation,
calix[4]arenes 13 were isolated in 32–45% yields by col-
umn chromatography (SiO2, benzene/ethyl acetate = 2/1).
Each enantiomer of 13 could be separated by chiral
HPLC column (Chiralpak AD, hexane/2-propanol =
23/1 as an eluent).3,11
which is a typical feature of the rotation around the
CH2 axis. Then, we concluded that 5 and 13 took com-
pletely the cone-type (syn) conformation, but 8 took
several conformations like the partial-cone or the
1,2-alternate form.
The cyclobutane methine protons of 5 and 8 locate at d
4.40–4.42 and 4.48–4.58, respectively, and those of 13 lo-
cate in two parts at d 4.24–4.38 and 4.50–4.64 to demon-
strate the typical cis configuration by the molecular
symmetry.1,4 The methoxy groups of 5 and 8 show a sin-
glet at d 3.56–3.60 and 3.70–3.76, respectively, and those
of 13 show two singlets at d 3.61–3.76 and 3.80–3.96 by
the molecular symmetry.1 Thus, the introduction of a
cyclobutane ring can suppress the rotation of the neigh-
boring benzene rings to keep the syn structure.
The structure of 5, 8 and 13 was mainly elucidated by 1H
NMR spectroscopy.12 All protons could be assigned in
the usual way by using several experiments like COSY
and NOESY and considering the molecular symmetry
of achiral structure 5 and 8 and chiral structure 13.
The benzylic methylene protons of 5 and 13 show AB-
type coupling (d 3.76–3.82 and 3.86–4.02 with J = 15–
16 Hz for 5 and d 3.60–3.62 and 4.04–4.41 with
J = 15 Hz for 13),2 which is the same as those ascribed
to the parent calix[4]arene cone-form. On the other
hand, those of 8 show a singlet peak at d 3.84–3.86,
The complexation was examined by the addition of K+
salt in solution of calixarene analogs 5, 8, and 13. Most
of their peaks shifted after the addition of a metal
ion (1 equiv). JobÕs plots clearly demonstrate that

Y. Okada et al. / Tetrahedron Letters 46 (2005) 3261–3263
3263
a
Table 1. Extraction (%) of alkali metal picrates in CH2Cl2
+
Compd
Li+
Na+
K+
Rb+
Cs+
<1
NH4
5a
5b
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
1.5
1.6
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
3.7
13.0
<1
2.8
3.3
<1
<1
<1
<1
1.6
1.4
<1
5c
8a
8b
8c
4.6
9.7
<1
4.3
10.5
<1
1.5
2.2
<1
13a
13b
13c
2.0
2.1
3.9
4.7
<1
<1
a Extraction conditions: 2.5 · 10À4 M of ionophore in CH2Cl2; 2.5 · 10À5 M of picric acid in 0.01 M of MOH at 22 ꢁC. Ionophore solution (5.0 ml)
was shaken (10 min) with picrate solution (5.0 ml) and % extraction was measured by the absorbance of picrate in CH2Cl2. Experimental error was
2%.
7. Calixarenes 50th Anniversary; Vicens, J., Asfari, Z.,
Harrowfield, J. M., Eds.; Kluwer: Dordrecht, 1994.
8. Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713.
9. Okada, Y.; Ishii, F.; Kasai, Y.; Nishimura, J. Tetrahedron
Lett. 1993, 34, 1971.
calixarenes can form 1:1 complex with the alkali metal
ions. Based on this observation, we determined the
extractability of ionophores 5, 8, and 13 with alkali
metal ions from the aqueous phase to an organic
phase.13–17 The extraction experiments were carried
out with 2.5 · 10À4 M of ionophores in CH2Cl2 and
2.5 · 10À5 M of picric acid in 0.01 M of metal hydroxide
at 22 ꢁC. These results are summarized in Table 1. Gen-
erally speaking, they acted as ionophores, although the
extractability is moderate. Ionophores showed the
extractability for larger alkali metal ions like K+, Rb+,
and Cs+ rather than smaller ones like Li+ and Na+.
The best extractability for alkali metal ions among all
ionophores is exhibited by 8. This result suggests that
the crown ether ring of 8 was preorganized to bind the
metal ions by the rigid calixarene moiety attaching the
cyclobutane ring.
10. Okada, Y.; Kasai, Y.; Nishimura, J. Tetrahedron Lett.
1995, 36, 555.
11. Okada, Y.; Mizutani, M.; Ishii, F.; Nishimura, J. Tetra-
hedron Lett. 1997, 38, 9013.
1
12. Compd: H NMR d (intensity, multiplicity, J in Hz). 5a:
2.38 (2H, m), 2.45 (2H, m), 3.56 (6H, s), 3.60 (6H, m), 3.66
(2H, m), 3.76 (2H, d, 16), 3.94 (4H, m), 4.02 (2H, d, 16),
4.40 (2H, m), 6.66–6.80 (8H, m), 6.92–7.05 (4H, m), 7.16
(2H, m). 5b: 2.40 (2H, m), 2.46 (2H, m), 3.58 (6H, s), 3.62
(10H, m), 3.68 (2H, m), 3.81 (2H, d, 16), 3.87 (2H, m), 3.94
(2H, d, 16), 3.99 (2H, m), 4.41 (2H, m), 6.72–6.84 (10H,
m), 7.02–7.11 (4H, m). 5c: 2.40 (2H, m), 2.48 (2H, m),
3.40–3.80 (14H, m), 3.60 (6H, s), 3.82 (2H, d, 15), 3.82–
4.16 (6H, m), 3.86 (2H, d, 15), 4.42 (2H, m), 6.70–6.90
(10H, m), 7.01–7.16 (4H, m). 8a: 2.36 (2H, m), 2.50 (2H,
m), 3.58 (2H, m), 3.62–3.96 (8H, m), 3.76 (6H, s), 3.84
(4H, s), 3.92 (2H, m), 4.58 (2H, m), 6.58–6.92 (10H, m),
7.03–7.16 (4H, m). 8b: 2.38 (2H, m), 2.48 (2H, m), 3.56–
3.80 (14H, m), 3.72 (6H, s), 3.80–3.90 (2H, m), 3.86 (4H,
s), 4.53 (2H, m), 6.62–6.88 (10H, m), 7.04–7.16 (4H, m).
8c: 2.40 (2H, m), 2.50 (2H, m), 3.58–3.80 (18H, m), 3.82–
3.96 (2H, m), 3.70 (6H, s), 3.86 (4H, s), 4.48 (2H, m), 6.62–
6.90 (10H, m), 7.02–7.16 (4H, m). 13a: 2.34 (1H, m), 2.44
(1H, m), 2.61 (1H, m), 3.14 (1H, m), 3.50–3.92 (12H, m),
3.62 (2H, d, 15), 3.76 (3H, s), 3.96 (3H, s), 4.24 (1H, m),
4.41 (2H, d, 15), 4.64 (1H, m), 5.96–6.54 (4H, m), 6.65–
6.98 (5H, m), 7.03–7.22 (5H, m). 13b: 2.36 (3H, m), 2.52
(1H, m), 3.40–3.68 (10H, m), 3.60 (2H, d, 15), 3.61 (3H, s),
3.70–3.86 (4H, m), 3.80 (3H, s), 4.04 (2H, m), 4.10 (2H, d,
15), 4.24 (1H, m), 4.50 (1H, m), 6.37–6.86 (9H, m), 6.94–
7.34 (5H, m). 13c: 2.42 (2H, m), 2.52 (2H, m), 3.56–3.70
(12H, m), 3.60 (2H, d, 15), 3.62 (3H, s), 3.74–3.86 (6H, m),
3.80 (3H, s), 4.04 (2H, d, 15), 4.10 (2H, m), 4.38 (1H, m),
4.50 (1H, m), 6.54–6.82 (8H, m), 6.84–7.22 (6H, m).
13. Okada, Y.; Mizutani, M.; Ishii, F.; Kasai, Y.; Nishimura,
J. Tetrahedron 2001, 57, 1219.
In conclusion, all regioisomers of new calix[4]arene ana-
logs were synthesized in good yields. They formed a
complex with alkali metal ions and extracted larger
metal picrates rather than small ones. Further investiga-
tion is now in progress and will be reported elsewhere.
Acknowledgements
This work was supported by grants from the Ministry of
Education, Culture, Sports, Science, and Technology,
Japan.
References and notes
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