Facile synthesis of cone p-tert-butylcalix[4]arene-crown conformers

Article abstract of DOI:10.1016/j.mencom.2007.11.010

The series of p-tert-butylcalix[4]arene-crowns in the cone conformation was synthesised in high yields under conditions producing disubstituted calix[4]arenes in the presence of K₂CO₃ in acetonitrile; the formation of calix-bis(crown)s and doubly(calix)-doubly(crown) in these reactions was established.

Full text of DOI:10.1016/j.mencom.2007.11.010

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 330–331
Facile synthesis of cone p-tert-butylcalix[4]arene-crown conformers
Elena A. Alekseeva,* Stepan S. Basok, Alexander V. Mazepa and Andrei I. Gren
A. V. Bogatsky Physico-Chemical Institute, National Academy of Sciences of Ukraine, 65080 Odessa, Ukraine.
Fax: +38 0482 65 2012; e-mail: Alyeksyeyeva@rambler.ru
DOI: 10.1016/j.mencom.2007.11.010
The series of p-tert-butylcalix[4]arene-crowns in the cone conformation was synthesised in high yields under conditions
producing disubstituted calix[4]arenes in the presence of K2CO3 in acetonitrile; the formation of calix-bis(crown)s and
doubly(calix)-doubly(crown) in these reactions was established.
Although bridging chains are the most important factors in the
complexation of calixcrowns, the presence of lipophilic groups
at the upper rim of a calixarene moiety also plays a relevant
role in determining the selectivity.1–7 The synthesis of cone
conformers of p-tert-butylcalix[4]arene-crowns-5(6,7) with
poly(ethylene glycol) ditosylates in refluxing benzene in the
presence of ButOK was reported previously.8 The yields of
crowned products strongly depend on the lengths of bridging
fragments (15–55%). Moreover, the isolation and purification
of the crude product are difficult to perform. p-tert-Butylcalix-
[4]arene-crown-4 was usually prepared by a two-step reaction
from a calixarene derivative with the residue of triethylene
glycol with the tosyl group at the end of this fragment. For
synthesis of biscrowned p-tert-butylcalix[4]arenes the either
method of protected groups or alkylation of calixarene with
polyethylene glycol ditosylates in the presence of a strong base
(NaH) were used.9–11
Therefore, we studied the introduction of oligo(ethylene
glycol) chains with different numbers of donor centres into the
molecules of p-tert-butylcalix[4]arene 1 and used experimental
conditions similar to the procedure leading to the disubstituted
calix[4]arenes in the cone conformation in the presence of
K2CO3 in acetonitrile.12 At the same time, the systematic study
of the leaving group effect on the reaction was carried out.
The reaction of 1 with 2.2 equiv. of oligo(oxa)alkane
diiodides containing from two to five oxygen atoms in the
presence of 2.3 equiv. of K2CO3 in refluxing acetonitrile
produced 1,3-p-tert-butylcalix[4]crowns-4(5–7) 2–5 in a cone
conformation in 60–85% yields. The unexpected result was
found with the use of 1,8-diiodo-3,6-dioxaoctane when doubly-
(calix[4]arene)-doubly(crown-4) 6 was isolated in > 30% yield.
1
The H NMR spectrum of 2 indicated that the calixarene units
are in a cone conformation and linked by distal glycol chains in
1,3–1,3-positions: one AB system from the methylene protons
of the macrocycles, two singlets from tert-butyl protons and
two singlets from the protons of aromatic rings with 1:1. The
interaction of p-tert-butylcalix[4]arene with 1,11-diiodo-3,6,9-
trioxaundecane leads to a mixture of the desired product and a
small amount of calix[4]arene-crown-5 with the residue of
11-iodo-3,6,9-trioxaundecane.
The change of the iodide ion by the tosyloxy group results
in the formation of crowned compounds in 70–95% yields. In
case of using the ditosylates of triethylene glycol, 1,2-bridged
p-tert-butylcalix[4]arene-bis(crown-4) 7 was formed as a by-
product in 15% yield, instead of interaction with bromides of
3,6-dioxaoctane or 3,6,9-trioxaundecane, when 1,2-calix[4]-
arene-bis(crown-4) and bis(crown-5) 8 were formed in almost
25% yields.
But
But
But
But
But
But
But
But
But
But
But
But
O
O
O
O
Lg
O
O
Lg
n
OH
HO
2.2 equiv.
,
,
OH
O
O
O
K2CO3 (2.3 equiv.)
MeCN
HO
OH
O
HO
O
OH
OH
O
O
OH
But
But
HO
O
But
But
1
Lg = I, Br, TsO, MsO, PhSO2O
2–5
n = 1–4
6 Lg = I (30%)
But
But
But
But
But
But
But
But
,
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
7 Lg = TsO (15%) or Br (25%)
8 Lg = Br (25%)
Scheme 1
– 330 –
© 2007 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2007, 17, 330–331
References
Table 1 Yields of calixcrowns 2–5.
1
C. Alfieri, E. Dradi, A. Pochini, R. Ungaro and G. D. Adreetti, J.
Chem. Soc., Chem. Commun., 1983, 1075.
Yields of calixcrowns (%)
Lg
2
P. J. Dijkstra, J. A. Brunink, K.-E. Bugge, D. N. Reinhoudt, S. Harkema,
R. Ungaro, F. Ugozzoli and E. Ghidini, J. Am. Chem. Soc., 1989, 111,
7567.
V. Lamare, J.-F. Dozol, F. Ugozzoli, A. Casnati and R. Ungaro, Eur. J.
Org. Chem., 1998, 1559.
T. Jin, J. Chem. Soc., Perkin Trans. 2, 2002, 151.
B. Pipoosananakaton, M. Sukwattanasinitt, N. Jaiboon, N. Chaichit and
Th. Tuntulani, Tetrahedron Lett., 2000, 41, 9095.
A. P. Marchand, H.-S. Chong, T. P. Kumar, Z. Huang, S. Alihodzic,
W. H. Watson and K. Ejsmont, Tetrahedron, 2002, 58, 10205.
Z. Asfari, S. Wenger and J. Vicens, Supramol. Sci., 1994, 1, 103.
J. Dozol, H. Rouquette, R. Ungaro and A. Casnati, US Patent, 5926687,
B01D, 1999.
2
3
4
5
I
60
70–75
70
85
90
70
85
90
87
85
95
90
TsO
Br
MsO or PhSO3
3
65–70
3 + 4 + 5: 60–65
4
5
However, the reaction between H-calix[4]arene 9 and di-
iodides of oligo(oxa)alkanes or ditosylates of oligo(ethylene
glycols) yielded only calix[4]arene-crown-4(5,6) ethers 10–12
(65–75%).
Thereupon, the alkylation of calixarene 1 with mesylates and
phenylsulfonates of oligo(ethylene glycols) resulted in only
crowned compounds but with a large amount of unconverted
p-tert-butylcalix[4]arene (about 30–35%) (Scheme 1, Table 1).
All calix[4]arene-crown ethers were isolated by simple re-
crystallization from alcohols without column chromatography
or HPLC.†
6
7
8
9
Y. He, Y. Xiao, L. Meng, Zh. Zeng, Z. Wu and Ch.-T. Wu, Tetrahedron
Lett., 2002, 43, 6249.
10 H. Yamamoto, T. Sakaki and S. Shinkai, Chem. Lett., 1994, 469.
11 A. Arduini, A. Casnati, L. Dodi, A. Pochini and R. Ungaro, J. Chem.
Soc., Chem. Commun., 1990, 1597.
12 K. Iwamoto, K. Araki and S. Shinkai, Tetrahedron, 1991, 47, 4325.
Thus, the method proposed for the preparation of p-tert-butyl-
calix[4]crowns in a cone conformation leads to desired products
in good yields. We found that the formation of calixbis(crown)
and doubly(calix)-doubly(crown) as by-products depends on the
structure of the bridging chain and the nature of the leaving
group in the alkylating agent. In the interaction of calix[4]arene
with diiodides of oligo(oxa)alkanes or ditosylates of oligo-
(ethylene glycols), only the calixarene-crowns were formed.
Received: 2nd April 2007; Com. 07/2901
5: mp 235–236 °C. 1H NMR d: 0.80 (s, 18H, But), 1.21 (s, 18H, But),
3.40 (d, 4H, ArCH2Ar, J 13.5 Hz), 3.70–4.21 (m, 24H, OCH2CH2O),
4.45 (d, 4H, ArCH2Ar, J 13.5 Hz), 6.84 (s, 4H, ArH), 7.10 (s, 4H, ArH),
7.30 (s, 2H, OH). FAB-MS, m/z: 895 (M + H)+. Found (%): C, 75.07;
H, 8.84. Calc. for C56H78O9 (%): C, 75.13; H, 8.78.
6: mp 156 °C. 1H NMR, d: 1.20 (s, 36H, But), 1.23 (s, 36H, But), 3.34
(d, 8H, ArCH2Ar, J 12.3 Hz), 3.93 (s, 8H, OCH2CH2O), 4.14–4.23 (m,
16H, OCH2CH2O), 4.37 (d, 8H, ArCH2Ar, J 12.3 Hz), 7.00 (s, 8H, ArH),
7.09 (s, 8H, ArH), 8.50 (s, 4H, OH). FAB-MS, m/z: 1521 (M + H)+.
Found (%): C, 78.62; H, 8.77. Calc. for C100H132O12 (%): C, 78.70; H, 8.72.
7: mp 184–186 °C. 1H NMR, d: 1.19 (s, 18H, But), 1.20 (s, 18H, But),
3.18 (d, 2H, ArCH2Ar, J 14 Hz), 3.34 (d, 2H, ArCH2Ar, J 14 Hz), 3.98
(s, 8H, OCH2CH2O), 4.16–4.21 (m, 16H, OCH2CH2O), 4.40 (d, 2H,
ArCH2Ar, J 14 Hz), 4.65 (d, 2H, ArCH2Ar, J 14 Hz), 7.00 (s, 4H, ArH),
7.09 (s, 4H, ArH). FAB-MS, m/z: 876 (M + H)+. Found (%): C, 76.60;
H, 8.78. Calc. for C56H76O8 (%): C, 76.68; H, 8.73.
†
1H NMR spectra were recorded on a Varian VXR-300 (300 MHz)
spectrometer using CDCl3 as a solvent and TMS as an internal standard.
Mass spectra were recorded on MX-1321 and VG 70-70EQ spectro-
meters; FAB mass spectra were measured on a VG 70-70EQ mass
spectrometer using m-nitrobenzyl alcohol as a matrix.
General procedure for the calixarene-crowns: a suspension of p-tert-butyl-
calix[4]arene 1 (4 mmol, 2.96 g) or calix[4]arene 9 (4 mmol, 1.69 g) and
K2CO3 (9.2 mmol, 1.27 g) in dry MeCN (80 ml) was stirred for 30 min;
then, the solution of a corresponding alkylation agent (8.8 mmol) in 50 ml
of MeCN was added dropwise for 45 min. After stirring for 12–14 (in
case of the iodide ion), 8–12 (tosyloxy or bromide ion) or 18–20 h (mesyl
or phenylsulfonate), the reaction was stopped; the inorganic precipitate
was filtered off; the solution was vacuum concentrated to leave a residue,
which was dissolved in CHCl3, washed with 10% HCl and water and
then dried over MgSO4. The evaporation of the solvent afforded a white
solid crude product, which was purified by crystallization from alcohols.
The doubly crowned compounds were isolated from the crude mixture
by trituration in hot hexane or heptane and then purified by recrystal-
lization from alcohol–water. Monocrowned calixarenes were purified by
recrystallization from methanol or ethanol.
8: mp 195–197 °C. 1H NMR, d: 1.17 (s, 18H, But), 1.19 (s, 18H, But),
3.20 (d, 2H, ArCH2Ar, J 14.2 Hz), 3.60 (d, 2H, ArCH2Ar, J 14.2 Hz),
3.70–4.30 (m, 32H, OCH2CH2O), 4.50 (d, 2H, ArCH2Ar, J 14.7 Hz),
4.75 (d, 2H, ArCH2Ar, J 14.7 Hz), 6.87 (s, 4H, ArH), 7.00 (s, 4H, ArH).
FAB-MS, m/z: 966 (M + H)+. Found (%): C, 74.58; H, 8.82. Calc. for
C60H84O10 (%): C, 74.65; H, 8.77.
2: mp 262–264 °C. 1H NMR, d: 0.95 (s, 18H, But), 1.29 (s, 18H, But),
3.27 (d, 4H, ArCH2Ar, J 13.53 Hz), 4.00–4.15 (m, 12H, OCH2CH2O),
4.37 (d, 4H, ArCH2Ar, J 13.53 Hz), 6.79 (s, 4H, ArH), 7.05 (s, 4H,
ArH), 7.39 (s, 2H, OH). FAB-MS, m/z: 763 (M + H)+. Found (%): C,
78.78; H, 8.81. Calc. for C50H66O6 (%): C, 78.70; H, 8.72.
3: mp 250–252 °C. 1H NMR, d: 0.94 (s, 18H, But), 1.34 (s, 18H, But),
3.35 (d, 4H, ArCH2Ar, J 13.0 Hz), 3.80–4.15 (m, 16H, OCH2CH2O),
4.43 (d, 4H, ArCH2Ar, J 13.0 Hz), 6.8 (s, 4H, ArH), 7.15 (s, 4H, ArH),
7.20 (s, 2H, OH). FAB-MS, m/z: 807 (M + H)+. Found (%): C, 77.31;
H, 8.80. Calc. for C52H70O7 (%): C, 77.38; H, 8.74.
4: mp 240–242 °C. 1H NMR, d: 0.85 (s, 18H, But), 1.25 (s, 18H, But),
3.20 (d, 4H, ArCH2Ar, J 13.2 Hz), 3.65–4.10 (m, 20H, OCH2CH2O),
4.31 (d, 4H, ArCH2Ar, J 13.2 Hz), 6.75 (s, 4H, ArH), 6.98 (s, 4H, ArH),
7.00 (s, 2H, OH). FAB-MS, m/z: 851 (M + H)+. Found (%): C, 76.12;
H, 8.81. Calc. for C54H74O8 (%): C, 76.20; H, 8.76.
10: mp 381–382 °C. 1H NMR, d: 3.32 (d, 4H, ArCH2Ar, J 12.48 Hz),
3.91 (s, 4H, OCH2CH2O), 4.20–4.28 (m, 8H, OCH2CH2O), 4.40 (d, 4H,
ArCH2Ar, J 12.48 Hz), 6.60 (t, 2H, ArH, J 7.3 Hz), 6.85 (t, 2H, ArH,
J 7.3 Hz), 7.04 (d, 4H, ArH, J 7.5 Hz), 7.08 (d, 4H, ArH, J 7.5 Hz), 8.84
(s, 2H, OH). FAB-MS, m/z: 539 (M + H)+.
11: mp 268 °C. 1H NMR, d: 3.35 (d, 4H, ArCH2Ar, J 13.2 Hz), 3.80–
4.15 (m, 16H, OCH2CH2O), 4.43 (d, 4H, ArCH2Ar, J 13.2 Hz), 6.68
(t, 2H, ArH, J 7.5 Hz), 6.75 (t, 2H, ArH, J 7.5 Hz), 6.95 (d, 4H, ArH,
J 7.5 Hz), 7.04 (d, 4H, ArH, J 7.5 Hz), 7.87 (s, 2H, OH). FAB-MS, m/z:
584 (M + H)+.
1
12: mp 230–232 °C. H NMR, d: 3.38 (d, 4H, ArCH2Ar, J 13.4 Hz),
3.80 (s, 4H, OCH2CH2O), 3.85–3.94 (m, 4H, OCH2CH2O), 4.00–4.10 (m,
12H, OCH2CH2O), 4.43 (d, 4H, ArCH2Ar, J 13.4 Hz), 6.65 (t, 2H, ArH,
J 7.5 Hz), 6.72 (t, 2H, ArH, J 7.5 Hz), 6.88 (d, 4H, ArH, J 7.5 Hz), 7.04
(d, 4H, ArH, J 7.5 Hz), 7.52 (s, 2H, OH). FAB-MS, m/z: 627 (M + H)+.
– 331 –