Syntheses of novel types of calix [6]bis-crowns and related compounds

Article abstract of DOI:10.1039/b007408j

The syntheses of novel types of p-tert-butylcalix[6]bis-crowns and related compounds is described. By reacting p-tert-butylcalix[6]-1,4-crown-4 with ethylene glycol ditosylate or polyethylene glycol ditosylates using NaH as a base in DMF, p-tert-butylcalix[6]-2,3-ethylene-1,4-crown-4, p-tert-butylcalix[6]-1,4-crown-4-2,6-crown-3, monotosyloxyethoxyethyl-p-tert-butylcalix[6]-1,4-crown-4, p-tert-butylcalix[6]-1,4-crown-4-2,5-benzocrown-4 and p-tert-butylcalix[6]-1,4-crown-4-2,6-crown-5 were obtained in reasonable yields under selective conditions.

Full text of DOI:10.1039/b007408j

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Syntheses of novel types of calix[6]bis-crowns and related compounds
Yuanyin Chen* and Haibing Li
Department of Chemistry, W uhan University, W uhan 430072, P. R. China.
E-mail: yychen=whu.edu.cn
Received (in Montpellier, France) 6th September 2000, Accepted 24th October 2000
First published as an Advance Article on the web 21st December 2000
The syntheses of novel types of p-tert-butylcalix[6]bis-crowns and related compounds is described. By reacting
p-tert-butylcalix[6]-1,4-crown-4 with ethylene glycol ditosylate or polyethylene glycol ditosylates using NaH as a
base in DMF, p-tert-butylcalix[6]-2,3-ethylene-1,4-crown-4, p-tert-butylcalix[6]-1,4-crown-4-2,6-crown-3,
monotosyloxyethoxyethyl-p-tert-butylcalix[6]-1,4-crown-4, p-tert-butylcalix[6]-1,4-crown-4-2,5-benzocrown-4 and
p-tert-butylcalix[6]-1,4-crown-4-2,6-crown-5 were obtained in reasonable yields under selective conditions.
Calixcrowns comprise a family of calixarenes in which the
phenolic oxygens are linked intramolecularly via Ñexible
poly(oxyethylene) chains.1 As they possess preorganized struc-
tures and more rigid binding sites in comparison with calix-
arenes and crown ethers, they exhibit superior recognition
ability toward alkali metal ions and other ions by the co-
operative e†ects of calixarene and crown moieties. In particu-
lar, calix[4]arene crown-6 hosts have been investigated for the
sequestration and removal of radioactive 137Cs from aqueous
waste mixtures.2 At present, as calix[4]crown chemistry
systematic investigation on the condensation of p-tert-
butylcalix[6]-1,4-crown-4, 1, with ethylene glycol ditosylate, 6,
diethylene glycol ditosylate, 5, 1,2-bis(tosyloxyethoxy)benzene,
4, and tetraethylene glycol ditosylate, 2. Under selected condi-
tions, a series of positional isomers of calix[6]bis-crowns and
related compounds have been prepared in reasonable yields as
outlined in Scheme 1.
Results and discussion
Syntheses and characterization
approaches
maturity
not
only
many
types
of
calix[4]monocrowns, but also many types of calix[4]bis-
crowns have been synthesized.3h9 Their recognition properties
toward Cs`, K`, etc. have been studied as well.10h14
However, in contrast to the extensive investigations on
calix[4]bis-crowns, very little is known about calix[6]bis-
crowns.
Just recently, Blanda et al. reported the Ðrst examples of
calix[6]bis-crowns: 1,4-diallyloxycalix[6]-2,6-3,5-bis-crown-
4s,15 as shown in Fig. 1. Meanwhile, Chen et al. have also
synthesized p-tert-butylcalix[6]-1,4-2,5-bis-crown-4, 8, and
p-tert-butylcalix[6]-1,4-benzocrown-4-2,5-crown-4, 9, from
p-tert-butylcalix[6]-1,4-crown-4, 1, or p-tert-butylcalix[6]-1,4-
benzocrown-4 by reacting them with triethylene glycol ditosy-
late, 3.16 As an extension of the above work, we report here a
The synthetic route is depicted in Scheme 1. p-tert-
Butylcalix[6]-1,4-crown-4, 1, has been obtained by reacting
p-tert-butylcalix[6]arene with triethylene glycol ditosylate in
K CO ÈCH CN as a mixture of p-tert-butylcalix[6]-1,4-
crown-4 and p-tert-butylcalix[6]-1,3-crown-4 in yields of 20
and 11% respectively.17 However the yield of 1 can be
increased to nearly 40% by using toluene as the solvent
instead of MeCN, and the work-up was simpliÐed in compari-
son with the original method.16
Further treatment of 1 with diethylene glycol ditosylate, 5,
1,2-bis(tosyloxyethoxy) benzene, 4, or tetraethylene glycol
ditosylate, 2, in the presence of NaH as a base in DMF gave
11 plus 10, 9 and 7 in yields of 35, 16, 60 and 32% respec-
tively. No separable product has been obtained from 1 with
2
3
3
Scheme 1 Reagents and conditions: (i) K CO (9.0È10.0 equiv.), toluene, reÑux, 24 h. (ii) NaH, DMF, 60 ¡C, 7È12 h. (iii) NaH, THF-DMF (10 : 1
2
3
v/v), reÑux, 24 h. (iv) NaH, THF, reÑux, 2 days.
340
New J. Chem., 2001, 25, 340È343
DOI: 10.1039/b007408j
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001

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Scheme 2 7* and 10* are the possible conformers of 7 and 10, respectively.
ethylene glycol distosylate, 6, under the above conditions.
After much e†ort, we found Ðnally that by using THFÈDMF
(10 : 1 v/v), instead of DMF alone, the reaction product was
easily separated and the desired product 12 was obtained in
23% yield.
features of 10 are very similar to those of 7. However, as the
(u,d,d,u,d,d) and (u,d,u,u,u,d) conformations will both give
similar NMR data for methylene protons, it is not possible to
assign the conformation, although we believe the former is
more plausible (as shown in Scheme 2).
Compound 9 has been synthesized by a di†erent route from
p-tert-butylcalix[6]-benzocrown-4 before.16 The structures of
7, 10, 11 and 12 (shown in Scheme 2) were conÐrmed by 1H
NMR FAB-MS and elemental analysis. The 1H NMR spec-
trum of 7 shows four singlets (ratio 1 : 2 : 2 : 1) for the tert-
butyl groups, three pairs of doublets (one is mixed with
ethylene protons) for the methylene protons, and one singlet
for the hydroxyl protons. This is in accord with the structure
of p-tert-butylcalix[6]-1,4-crown-4-2,6-crown-5, 7. Compound
10 gives satisfactory elemental analysis results and shows the
expected molecular ion peak in the mass spectrum. The 1H
NMR spectrum of 10 shows four singlets (ratio 1 : 2 : 2 : 1) for
the tert-butyl groups, three pairs of doublets (two are mixed
with ethylene protons) for the methylene protons, and one
singlet for the hydroxyl protons. This is in accord with the
structure of p-tert-butylcalix[6]-1,4-crown-4-2,6-crown-3, 10.
It is worth noting that most of the above mentioned spectral
The 1H NMR spectrum of 11 shows one singlet at d 2.44
and a pair of doublets at d 7.25 and 7.80 for the tosyloxy
group, and six singlets for the tert-butyl groups, obviously
indicating that the structure of 11 is asymmetrical. It is hard
to conÐrm the conformation of 11 at ambient temperature due
to the overlapping signals in the region of d 3.50È4.15.
The fact that compounds 10 and 11 were isolated in the
condensation of 1 and 5 suggests that 11 may be a possible
intermediate for 10. ReÑuxing 11 in THF in the presence of
NaH for two days, a small amount of 10 could be isolated.
This can be considered as indirect evidence for the structure of
11.
The elemental analysis data of 12 are in accordance with
the molecular formula C
H
O . The FAB-MS spectrum
74 96
8
shows the expected molecular ion peak at m/z 1112. The 1H
NMR spectrum of 12 shows three singlets (1 : 1 : 1) for tert-
butyl groups as well as the aromatic protons, one singlet for
New J. Chem., 2001, 25, 340È343
341

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Comment
The syntheses of a series of calix[6]bis-crowns is reported here
and the work may promote the syntheses of new types of
calix[6]bis-crowns and their application in supramolecular
chemistry.
Experimental
Melting points were recorded on a Gallenkamp melting point
apparatus in open capillaries and are uncorrected. 1H NMR
spectra were recorded on a Varian Mercury VX300 instru-
ment at ambient temperature. TMS was used as an internal
standard for NMR. FAB-MS spectra was obtained from a
Kratos MS80RF mass spectrometry service, with m-
nitrobenzyl alcohol as a matrix. Elemental analyses were per-
formed by the Analytical Laboratory of the Department of
Chemistry, Wuhan University. All solvents were puriÐed by
standard produres. Petroleum ether refers to the fraction with
bp 60È90 ¡C. All other chemicals were analytically pure and
used without further puriÐcation.
Syntheses
Fig. 1 1,2,3-Alternate conformation and cone conformation
Improved procedure for the synthesis of 1,4-p-tert-
butylcalix[6]crown-4, 1.16 A mixture of p-tert-butylcalix[6]
arene (5 mmol), triethylene glycol ditosylate (5.5 mmol), and
anhydrous K CO (50 mmol) in toluene (500 ml) was stirred
calix[6]bis-crowns.
2
3
and reÑuxed under N for 24 h. After the solvent was removed
the hydroxyl protons, and four pairs of doublets (ratio
1 : 2 : 2 : 1) for the methylene protons in the calixarene skele-
ton (one of which is perturbed by superposition with the
peaks of the spacers). The data support that 12 is p-tert-
butylcalix[6]-2,3-ethylene-1,4-crown-4 and 12 adopts the (u,u,
u,u,u,u) cone conformation at ambient temperature.
2
under reduced pressure, the residue was treated with HCl
(10%, v/v) and extracted with CHCl . The organic layer was
3
separated, dried by MgSO and Ðltered. The organic phase
4
was evaporated again. The crude product was subjected to
recrystallization from CHCl and petroleum ether (60È90 ¡C)
3
to a†ord 1 in 40% yield. Its spectra are the same as those
reported in ref. 17.
Extraction abilities
Examination of the CPK molecular models reveals that com-
pounds 12, 10, 9, 8 and 7 are well preorganized to extract
cations. p-tert-Butylcalix[6]1,4-crown-4, 1, is used as the refer-
ence compound. The percentage extraction of seven picrate
General procedure for the synthesis of compounds 7, 9, 10
and 11. A solution of p-tert-butylcalix[6]-1,4-crown-4, 1, in
freshly distilled DMF was treated with NaH at room tem-
perature for 30 min. Diethylene glycol ditosylate, 5, tetra-
ethylene glycol ditosylate, 2, or 1,2-bis(tosyloxyethoxy)-
benzene, 4, (1.2 equiv. in each case) was added. The reaction
mixture was then stirred at 60 ¡C for 7È12 h and the excess
NaH was destroyed by addition of a minimal quantity of
methanol (caution!). The mixture was evaporated to dryness
and the residue was treated with a solution of HCl (10% v/v)
and extracted with ethyl acetate. After puriÐcation by column
chromatography, compounds 7, 9, 10 and 11 were isolated as
white solids in yields of 32, 60, 16 and 35%, respectively.
salts by these six hosts from water into CHCl at 25 ^ 1 ¡C
3
was determined; the arithmetic mean of several experiments is
shown in Table 1; the standard deviation on the mean is
p
O 1. Comparing with compound 1, the extraction levels
N~1
of 12, 10, 9, 8 and 7 are higher, especially 12. This can be
attributed to the beneÐcial inÑuence of a second oxyethylene
bridge, which increases the rigidity of the calix[6]arene frame-
work, as compound 12 adopts a cone conformation at room
temperature. It is worthy of note that 10 shows high selectivity
towards Me NH `. To the best of our knowledge, 10 may be
7. Mp: 314È6 ¡C; 1H NMR (300 MHz, CDCl ): d 1.17 [s,
2
2
3
the Ðrst example of an ionophore with high Me NH ` selec-
tivity in calixarene chemistry.
9H, C(CH ) ], 1.24 [s, 18H, C(CH ) ], 1.26 [s, 18H, C(CH ) ],
2
2
3 3
3 3
3 3
1.32 [s, 9H, C(CH ) ], 2.35 (t, 4H, J \ 9.0, OCH CH ), 2.70
3 3
2
2
Table 1 Percentage extraction (%E) of picrate salts from water into CHCl at 25 ¡C.a %E is the arithmetic mean of several experiments. The
3
standard deviation on the mean is p
O 1
N~1
%E
Host
Li`
Na`
K`
NH `
Me NH `
Et NH `
n-PrNH `
4
2
2
2
2
3
7
8
2.4
1.4
0.3
4.3
1.1
15.3
2.6
6.9
5.2
1.2
7.8
3.5
11.0
6.5
5.9
18.9
9.5
7.6
16.2
12.4
2.3
6.3
28.2
4.0
12.8
11.4
6.4
3.6
12.1
12.0
6.5
4.8
24.1
19.3
7.8
31.4
2.9
9
10
11
12
1
5.6
3.6
4.4
10.5
25.5
4.5
15.3
40.7
3.8
14.3
32.3
5.6
a 1.00 ml of a 0.0025 mol dm~3 receptor solution in CHCl was shaken (20 min) with 1.00 ml of 0.005 mol dm~3 picrate salt solution in triply
3
distilled H O and the percentage extraction was measured from the resulting absorbance at 380 nm. Control experiments showed that no picrate
2
extraction occurred in the absence of the calixarene derivative.
342
New J. Chem., 2001, 25, 340È343

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(d, 2H, J \ 10.8, OCH CH ), 2.88 (q, 4H, J \ 10.5,
J \ 10.2, OCH CH ), 3.11 (t, 2H, J \ 9.0, OCH CH ), 3.24È
2
2
2
2
2
2
OCH CH ), 3.16 (q, 4H, J \ 10.5, OCH CH ), 3.31 (t, 4H,
3.55 (m, 9H, OCH CH and ArCH Ar), 3.70 (d, 1H, J \ 10.2,
2
2
2
2
2
2
2
J \ 9.0, OCH CH ), 3.44 (d, 2H, J \ 10.2, ArCH Ar), 3.53È
ArCH Ar), 3.85 (d, 1H, J \ 10.2, ArCH Ar), 4.03 (d, 2H,
2
2
2
2
2
3.64 (m, 12H, OCH CH and ArCH Ar), 3.87 (d, 2H,
J \ 17.1, ArCH Ar), 4.10 (d, 2H, J \ 13.5, ArCH Ar), 4.16 (d,
2
2
2
2
2
J \ 10.2, ArCH Ar), 4.08 (d, 2H, J \ 13.5, ArCH Ar), 4.17 (d,
1H, J \ 12.9, ArCH Ar), 4.34 (d, 2H, J \ 13.5, ArCH Ar),
2
2
2
2
2H, J \ 13.5, ArCH Ar), 4.47 (d, 2H, J \ 17.7, ArCH Ar),
4.43 (d, 2H, J \ 17.1 Hz, ArCH Ar), 6.73 (s, 4H, ArH), 7.05 (s,
2
2
2
6.54 (d, 2H, J \ 2.7, ArH), 6.72 (d, 4H, J \ 2.7, ArH), 6.95 (d,
4H, J \ 2.7, ArH), 7.14 (s, 2H, ArOH), 7.34 (d, 2H, J \ 2.7 Hz,
4H, ArH), 7.26 (s, 4H, ArH), 8.15 (s, 2H, ArOH); MS(FAB)
m/z: 1112 (M`). Anal. calc. for C
found: C, 79.85; H, 8.65%.
H
O : C, 79.82; H, 8.69;
74 96
8
ArH). MS(FAB) m/z: 1244 (M`). Anal calc. for C
H
O
:
80 108 11
C, 77.13; H, 8.74; found: C, 77.15; H, 8.71%.
9. The spectra of 9 are the same as those reported in ref. 16.
Acknowledgement
Financial support from the Natural Science Foundation of
China is gratefully acknowledged.
10. Mp: 276 ¡C (dec.); 1H NMR (300 MHz, CDCl ): d 1.16
3
[s, 9H, C(CH ) ], 1.24 [s, 18H, C(CH ) ], 1.26 [s, 18H,
3 3
3 3
C(CH ) ], 1.34 [s, 9H, C(CH ) ], 2.36 (t, 4H, J \ 8.7,
3 3 3 3
OCH CH ), 2.75 (t, 4H, J \ 9.0, OCH CH ), 3.00 (q, 4H,
2
2
2
2
J \ 10.5, OCH CH ), 3.19È3.58 (m, 12H, OCH CH and
2
2
2
2
ArCH Ar), 3.84 (d, 2H, J \ 10.5, ArCH Ar), 4.04 (d, 2H,
References
2
2
J \ 13.5, ArCH Ar), 4.13 (d, 2H, J \ 13.5, ArCH Ar), 4.42 (d,
2
2
1
2
H. Yamamoto and S. Shinkai, Chem. L ett., 1994, 1115.
Z. Asfari, B. Pulpoka, M. Saadioui, S. Wenger, M. Nierlich, P.
Thuery, N. Reynier, J.-F. Dozol and J. Vicens, J. Mol. Inclusion,
Recognit. Proc. 9th Int. Symp., 1998, 173.
2H, J \ 17.1, ArCH Ar), 6.50, 6.87, 6.93, 7.06, 7.21, 7.35 (d,
2
each 2H, J \ 2.4 Hz, ArH), 7.14 (s, 2H, ArOH); MS(FAB)
m/z: 1157 (MH`). Anal. calc. for C
8.71; found: C, 78.89; H, 8.69%.
H
O : C, 78.86; H,
76 100
9
3
4
5
6
A. Arduini, A. Casnati, L. Dodi, A. Pochini and R. Ungaro, J.
Chem. Soc., Chem. Commun., 1990, 1597.
11. Mp: 212È4 ¡C; 1H NMR (300 MHz, CDCl ): d 1.16,
3
1.21, 1.24, 1.26, 1.31, 1.34 [s, each 9H, C(CH ) ], 2.25 (t, 4H,
3 3
Z. Asfari, R. Abidi, F. Arnaud and J. Vicens, J. Inclusion Phenom.
Mol. Recognit. Chem., 1992, 13, 163.
J \ 9.0 Hz, OCH CH ), 2.44 (s, 3H, ArCH ), 2.71 (d, 2H,
2
2
3
Z. Asfari, S. Wenger and J. Vicens, Pure Appl. Chem., 1995, 67,
J \ 10.2, OCH CH ), 2.84 (q, 4H, J \ 9.0, OCH CH ), 3.20È
2
2
2
2
1037.
3.34 (m, 6H, OCH CH ), 3.42 (br s, 1H, ArCH Ar), 3.50È4.15
A. Arduini, L. Domiano, A. Pochini, R. Ungaro, F. Ugozzoli, O.
Struck, W. Verboom and D. N. Reinhoudt, T etrahedron, 1997,
53, 3767.
2
2
2
(m, 14H, OCH CH and ArCH Ar), 4.41 (d, 1H, J \ 15.3,
2
2
2
ArCH Ar), 6.43, 6.82, 6.85, 7.09, 6.88, 7.18 (s, each, 2H, ArH),
2
7.15 (br s, 2H, ArOH), 7.25 (d, 2H, J \ 8.4, ArH), 7.80 (d, 2H,
7
8
9
G. Ferguson, A. J. Lough, A. Notti and S. Pappalardo, J. Org.
Chem., 1998, 63, 9703.
J \ 8.4 Hz, ArH), 8.04 (br s, 1H, ArOH); MS(FAB) m/z: 1330
Z. Asfari, V. Lamare, J. F. Dozol and J. Vicens, T etrahedron
L ett., 1999, 40, 691.
(MH `). Anal. calc. for C
H
O S: C, 74.97; H, 8.19;
2
83 108 12
found: C, 74.95; H, 8.23%.
L. Nicod, S. PelletÈRostaing, F. Chirtry, M. Lemaire, H. Barnier
and V. Federici, T etrahedron L ett., 1998, 39, 4993.
Synthesis of compound 12. p-tert-Butylcalix[6]-1,4-crown-4,
1, was dissolved in THFÈDMF (10 : 1). To this solution, NaH
was added and the mixture was stirred for 30 min at room
temperature. Ethylene glycol ditosylate, 6 (1.2 equiv.), was
added via a syringe and the reaction mixture was heated to
reÑux for 24 h. The solvent was removed under reduced pres-
10 V. Lamare, J. F. Dozol, S. Fuangswassdi, F. Arnaud-Neu, P.
Thuery, M. Nierlich, Z. Asfari and J. Vicens, J. Chem. Soc.,
Perkin T rans. 2, 1999, 271.
11 Z. Asfari, V. Lamare, J. F. Dozol and J. Vicens, T etrahedron
L ett., 1999, 40, 691.
12 P. Thuery, M. Nierlich, J. C. Bryan, V. Lamare, J. F. Dozol, Z.
Asfari and J. Vicens, J. Chem. Soc., Dalton T rans., 1997, 4191.
13 H. H. Zeng and B. Dureault, T alanta, 1998, 46, 1485.
14 J. S. Kim, W. K. Lee, D. Y. Ra, Y. I. Lee, W. K. Choi, K. W. Lee
and W. Z. Oh, Microchem. J., 1998, 59, 464.
sure; the residue was redissolved in CHCl and washed with 1
3
N HCl and brine. The organic layer was dried over MgSO ,
4
Ðltered, concentrated, and then puriÐed by column chroma-
15 M. T. Blanda, D. B. Farmer, J. S. Brodbelt and B. J. Goolsby, J.
Am. Chem. Soc., 2000, 122, 1486.
tography on silica gel (CH Cl ÈEt O 5 : 3 v/v).
2
2
2
12. Mp: 244È6 ¡C; 1H NMR (300 MHz, CDCl ): d 1.12 [s,
16 Y. Y. Chen, F. F. Yang and X. R. Lu, T etrahedron L ett., 2000, 41,
3
18H, C(CH ) ], 1.18 [s, 18H, C(CH ) ], 1.26 [s, 18H,
C(CH ) ], 2.54 (t, 2H, J \ 9.0, OCH CH ), 2.73 (q, 4H,
3 3
1571.
3 3
3 3
2
17 J. S. Li, Y. Y. Chen and X. R. Lu, T etrahedron, 1999, 55, 10653.
2
New J. Chem., 2001, 25, 340È343
343