Stereoisomerism and complexation behaviour of functionalized p-tert-calix[6]-1,4-2,5-biscrown-4

Article abstract of DOI:10.1016/j.tetlet.2005.07.019

p-tert-Calix[6]-1,4-2,5-biscrown-4 was subjected to functionalization by benzyl bromide or ethyl bromoacetate. Two pairs of disubstituted calix[6]biscrown stereoisomers were obtained. Their structures had been deduced from ¹H NMR and ESI-MS (el

Full text of DOI:10.1016/j.tetlet.2005.07.019

Tetrahedron
Letters
Tetrahedron Letters46 (2005) 6041–6044
Stereoisomerism and complexation behaviour of functionalized
p-tert-calix[6]-1,4-2,5-biscrown-4
Bing Guan, Shuling Gong, Xiaojun Wu and Yuanyin Chen*
Department of Chemistry, Wuhan University, Wuhan 430072, PR China
Received 21 March 2005; revised 30 June 2005; accepted 5 July 2005
Available online 25 July 2005
Abstract—p-tert-Calix[6]-1,4-2,5-biscrown-4 was subjected to functionalization by benzyl bromide or ethyl bromoacetate. Two pairs
of disubstituted calix[6]biscrown stereoisomers were obtained. Their structures had been deduced from 1H NMR and ESI-MS (elec-
trospray ionization mass spectroscopy). One of the bisethyloxycarbonylmethylated derivatives 3a wasfurther investigated by X-ray
crystallographic analysis. Two-phase extraction experiments indicated that bisethyloxycarbonylmethylated derivatives exhibited
1
high Cs+/Na+ selectivity. By ESI-MS and H NMR experimentsit wasconfirmed that 3a formed 1:1 complex with Cs+.
ꢀ 2005 Published by Elsevier Ltd.
Calixcrowns, which are constructed by incorporating
crown ether segment into calixarene skeleton, play
unique rolesin the calixarene chemitsry due to their
outstanding selectivity towards alkali metal ions.1,2 In
2000, two types of calix[6]biscrowns, namely 1,4-2,5
and 1,3-4,6 double bridged calix[6]biscrowns, had been
reported for the first time.3–6 The 2,5-diallyl derivative
of calix[6]-1,3-4,6-biscrown-4 in the cone conformation
showed a high Cs+/Na+ selectivity and exhibited a cer-
tain extent extraction ability towardsK + ion.3 Recently,
we developed a convenient and simple method for the
synthesis of p-tert-calix[6]-1,4-2,5-biscrown-4.7 It isalso
well documented that the complexation ability of
calixarene towardsmetal ionscould be improved by
incorporating additional ligandssuch asCH 2COOC2H5,
CH2CONMe2, etc. Therefore, the derivatives, which are
based on the p-tert-calix[6]-1,4-2,5-biscrown-4 frame-
work could be a new candidate for ion receptorsbecause
of their more rigid conformation and polytopic binding
sites. Besides, it is possible to give stereoisomers in such
functionalized calixbiscrowns if the rotation of the func-
tionalized phenolic groupsisprohibited. To the best of
our knowledge, little isknown about the functionaliza-
tion of calix[6]biscrowns.8,9
of stereoisomerism as well as the strengthened complex-
ation ability and selectivity towards Cs+ ion of some
derivatives. The functionalization was performed as
shown in Scheme 1.
The reaction of p-tert-calix[6]arene (1) with triethylene
glycol ditosylates in xylene with K2CO3 asa base affor-
ded p-tert-calix-1,4-2,5-biscrown-4 (2) in 52% yield
conveniently.10 Further treatment of p-tert-butylca-
lix[6]-1,4-2,5-crown-4 with 2 equiv benzyl bromide or
ethyl bromoacetate in refluxing acetonitrile in the pres-
ence of 10 equiv K2CO3 for 12 h, gave two pairsof disub-
stituted derivatives, 3a and 3b, 4a and 4b in 65%, 23%,
52% and 34% yield, respectively. The structures of these
compoundswere characterized by ESI-MS spectra, ele-
mental analyses and 1H NMR studies.11 It isinteresting
to note that compounds 3a and 3b, or 4a and 4b both have
the same molecular weight. This indicated that 3a and 3b
should be a pair of stereoisomers. It was the same to 4a
and 4b. From their constructed pattern, the only possibil-
ity wastwo benzyl or ethyloxycarbonylmethyl groups
adopting different orientations(3,6- syn or 3,6-anti) and
they were a pair of stereoisomers as shown in Figure 1.
Asshown in Figure 1, the 3,6-syn-isomer has a C2 sym-
metry axis passing through the centre of calix[6]arene
cavity and the 3,6-anti-isomer has a horizontal C2 sym-
metry axisthrough the plane of the molecule. It wasin
Herein we wish to report our work on functionalizing
p-tert-butylcalix[6]-1,4-2,5-biscrown-4 (2), a new kind
1
agreement with that the H NMR spectra where three
*
singlets in a ratio of 1:1:1 for six tert-butyl groupswere
observed. The signals of tert-butyl of 3a appeared at
Corresponding author. Tel.: +86 27 8721 9184; fax: +86 27 8764
7617; e-mail: yychen@whu.edu.cn
0040-4039/$ - see front matter ꢀ 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.07.019

6042
B. Guan et al. / Tetrahedron Letters 46 (2005) 6041–6044
tBu
tBu
tBu
tBu
tBu
tBu
tBu
O
O
RO
O
O
HO
O
O
O
O
OR
O
O
OH
O
X
O
O
X
O
6
O
O
tBu
tBu
OH
tBu
tBu
tBu
tBu
1
2
3a, 3b
R= CH2COOC2H5
X = CH2CH2
4a 4b
3a + 3b
R= CH2Ar
ii
iii
i
2
1
4a + 4b
Scheme 1. Reagentsand condition:s (i) K 2CO3/xylene, triethylene glycol ditosylates, reflux, 12 h, 52%; (ii) K2CO3/MeCN, ethyl bromoacetate,
reflux, 12 h, 3a, 65%, 3b, 23%; (iii) K2CO3/MeCN, benzyl bromide, reflux, 12 h, 4a, 52%, 4b, 34%.
a =3,6-syn
C2
X
O
O
tBu
tBu
tBu
tBu
O
O
tBu
tBu
OR
O
O
RO
R
R
O
O
x
b=3,6-anti
X
O
C2
OtBu
tBu
RO
tBu
R
O
O
Figure 2. X-ray crystal structure of compound 3a.
tBu
OR tBu
tBu
O
O
R
O
O
The alkali metal binding propertiesof p-tert-butyl-
calix[6]-1,4-2,5-crown-4 derivativeswere invetisgated
using the metal picrate extraction method, in which
aqueous solutions of the picrate salts (2.0 · 10À3 M,
2 mL) were shaken with chloroform solutions of the
hosts (2.0 · 10À3 M, 2 mL) at 25 ꢁC.13 The result of
extraction studies was expressed as association constants
listing in Table 1.
x
X = CH2CH2
R= CH2Ar or CH2OOC2H5
Figure 1. Stereoisomers of disubstituted derivatives.
1.36, 1.22 and 1.16 ppm, and those of 3b appeared at
1.26, 1.23 and 1.18 ppm. It wasremarkable that one of
the signals in 3a appeared at much lower field
(1.36 ppm) ascompared with the other tert-butyl (near-
by 1.20 ppm). Secondly, there are six singlets (ratio of
1:1:1:1:1:1) for aromatic protonsin the 1H NMR spectra
of 3a, and for 3b the aromatic protonsappeared asfour
doubletsand one singlet in a ratio of 1:1:1:1:2. However,
it could not be assigned whether it was 3,6-syn-isomer
It wasworthy to note that the ethoxycarbonylmethyl
derivatives( 3a,b) have higher extraction ability and
selectivity towards Cs+ comparing to the parent calix-
biscrown (2) and the others. Especially, the Cs+/Na+
selectivity of compound 3a (3,6-syn-isomer) is higher
than that of compound 3b (3,6-anti-isomer). It was
proved again that the introduction of appropriate sub-
stituent onto special position could greatly increase the
binding ability of p-tert-calix[6]-1,4-2,5-biscrown-4
towardscertain metal ions.
1
or 3,6-anti-isomer by H NMR data alone. The unam-
biguous proof was obtained by a single crystal X-ray
analysis of 3a, which confirmed 3a with 3,6-syn-configu-
ration (Fig. 2). Detailsare given in the Experimental
section.12
Moreover, the stoichiometry of 3a with Cs+ wasinvesti-
gated. After 24 h precomplexation with 10 equiv of
Cs+PicÀ in chloroform/methanol (3:1), electrospray
mass spectrometry showed that only an intense peak
Based on the above discussion, the structure of 4a and
4b were deduced from similarity of their 1H NMR spec-
tra with 3a and 3b.

B. Guan et al. / Tetrahedron Letters 46 (2005) 6041–6044
6043
Table 1. Association constants (Ka · 10À5) for complexesof alkali
In conclusion, this paper described the synthesis of
disubstituted p-tert-butylcalix[6]-1,4-2,5-crown-4 and
the stereoisomerism of them. One of them (3a) wasfur-
ther investigated by single crystal X-ray analysis. We
found that the ethyloxycarbonylmethylated derivatives,
especially the 3,6-syn-isomer exhibited excellent com-
plexation ability and high selectivity towards Cs+ ions.
metalswith derivativesin CHCl deduced from metal picrate extrac-
3
tion data
2
3a
3b
4a
5.3
11.0
10.2
6.0
4b
Cs+
K+
Na+
Li+
7.8
9.2
12.2
6.5
900.0
130.0
3.8
150.0
24.1
2.6
3.8
5.5
9.4
8.0
5.0
3.0
Acknowledgements
Thank Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, for the single crystal
X-ray analysis.
References and notes
1. (a) Gutsche, C. D. Calixarene Revisited; Royal Society of
Chemistry: Cambridge, 1998; (b) Calixarenes 2001; Asfari,
Z., Bo¨hmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer
Academic: Dordrecht, The Netherlands, 2001.
2. Bohmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713–
745.
Figure 3. Electrospray ionization mass spectra for the complexation of
compound 3a with Cs+.
at m/z 1506.3 (Fig. 3) corresponding to the [3a+Cs+] ion
wasobserved. Thisindicated that only 1:1 complex was
formed even in the presence of an excess of Cs+PicÀ.
3. Blanda, M. T.; Farmer, D. B.; Brodbelt, J. S.; Goolsby, B.
J. J. Am. Chem. Soc. 2000, 122, 1486–1491.
4. Chen, Y. Y.; Yang, F. F.; Lu, X. R. Tetrahedron Lett.
2000, 41, 1571–1574.
5. Chen, Y. K.; Chen, Y. Y. Tetrahedron Lett. 2000, 41,
9079–9082.
6. Chen, Y. K.; Chen, Y. Y. Org. Lett. 2000, 2, 743–745.
7. Guan, B.; Gong, S. L.; Wu, X. J.; Li, Z. H.; Chen, Y. Y.
J. Incl. Phenom., in press.
8. Ko, S. W.; Yang, Y. S.; Mun, J. H.; Park, K. M.; Lee, S.
S.; Nam, K. C. Bull. Korean Chem. Soc. 2002, 23, 1379–
1380.
The result was also confirmed by 1H NMR experiments.
The changesof the chemical shiftsof free ligand 3a upon
addition of Cs+PicÀ were observed. Among them, the
change of one pair of tert-butyl protonswasremarkable
(Fig. 4). Itsdownfield hsift reached maximum by
Dd = 0.17 ppm when the molar ratio of Cs+PicÀ to
ligand 3a wasequal to 1:1, and no further change could
be observed by addition more Cs+PicÀ.
9. Ko, S. W.; Ryu, B. J.; Park, K. M.; No, K. H.; Kim, J. S.;
Nam, K. C. Bull. Korean Chem. Soc. 2004, 25, 957–958.
10. A mixture of 4.89 g (5.0 mmol) 1, 5.02 g (10.0 mmol)
triethylene glycol ditosylate, 2.11 g (15.2 mmol) anhydrous
K2CO3 and 500 mL xylene wastsirred at reflux temper-
ature for 12 h. After removal of solvent under reduced
pressure, the residue was treated with HCl (10%, v/v) and
extracted with CHCl3. The organic layer wasesparated,
dried over MgSO4, filtered and concentrated. After
recrystallization from mixture of chloroform and ethanol
(2:8, v/v), 3.13 g 2 was obtained as colourless crystal in
1
52% yield; 2: H NMR (300 MHz, CDCl3): 1.16 (36H, s,
ArC(CH3)3), 1.33 (18H, s, ArC(CH3)3), 2.86 (4H, t,
J = 9.0 Hz, OCH2 CH2), 3.25 (4H, q, J = 10.5 Hz,
OCH2CH2), 3.34–3.50 (16H, m, OCH2CH2 and
ArCH2Ar), 3.8 (4H, q, J = 10.5 Hz, OCH2CH2), 4.07
(4H, s, ArCH2Ar), 4.39 (4H, d, J = 15 Hz, ArCH2Ar),
6.91 (4H, s, ArH), 7.03 (2H, s, ArOH), 7.04 (4H, s, ArH),
7.11 (4H, s, ArH). FAB-MS: m/z = 1200 (M+, 100%).
Anal. Calcd for C78H104O10: C, 77.96; H, 8.72. Found: C,
78.10; H, 8.60.
11. General: Melting pointswere recorded on a Gallenkamp
melting point apparatusin open capillarieswithout
1
correction. H NMR wasrecorded on a Varian Mercury
VX300 instrument at ambient temperature with TMS as
an internal standard. ESI-MS was recorded on Finnigan
LCQ-Advantage instrument. All chemicals were A. R.
grade and purified by standard procedure. The procedure
for the synthesis of p-tert-butylcalix[6]-1,4-2,5-biscrown-4
derivatives: compound 2 (0.120 g, 0.1 mmol) was dissolved
in CH3CN (100 mL) and K2CO3 (0.139 g, 1.0 mmol)
Figure 4. tert-Butyl region of 1H NMR (300 MHz) spectra (CDCl3/
CD3OD, v/v = 4:1, 298 K) of (A): free ligand 3a; (B): 3a+0.5 equiv of
Cs+PicÀ; (C): 3a+1 equiv of Cs+PicÀ; (D): 3a+4 equiv of Cs+PicÀ.

6044
B. Guan et al. / Tetrahedron Letters 46 (2005) 6041–6044
added under a nitrogen atmosphere. After stirring 1 h,
4a: mp > 270 ꢁC; 1H NMR (300 MHz, CDCl3): 1.15 (s,
18H, C(CH3)3), 1.23 (s, 18H, C(CH3)3), 1.42 (s, 18H,
C(CH3)3), 2.18–2.20 (m, 2H, OCH2CH2), 2.49 (t,
J = 10.5 Hz, 2H, OCH2CH2), 2.60 (t, J = 10.5 Hz, 2H,
OCH2CH2), 2.88–2.97 (m, 4H, OCH2CH2), 3.08–3.21 (m,
4H, –OCH2CH2 and ArCH2Ar), 3.32 (d, J = 15 Hz, 2H,
ArCH2Ar), 3.39–3.49 (m, 4H, OCH2CH2 and ArCH2Ar),
3.49 (s, 2H, OCH2Ar) 3.58 (d, J = 15 Hz, 2H, ArCH2Ar),
3.61 (d, J = 15 Hz, 2H, ArCH2Ar), 3.90–4.08 (m, 6H,
OCH2CH2, ArCH2Ar and OCH2Ar), 4.29 (d, J = 15.6 Hz,
2H, ArCH2Ar), 4.72 (d, J = 15 Hz, 2H, ArCH2Ar), 4.73
(m, 4H, ArCH2Ar and OCH2Ar), 6.70 (s, 2H, ArH), 7.04
(s, 2H, ArH), 7.05 (s, 2H, ArH), 7.08 (s, 2H, ArH), 7.18 (s,
10H, ArH), 7.25 (s, 2H, ArH), 7.28 (s, 2H, ArH). MS
(ESI): m/z = 1381.9 (M+). Anal. Calcd for C92H116O10: C,
79.96; H, 8.46. Found: C, 79.92; H, 8.51; 4b: mp > 270 ꢁC;
1H NMR (300 MHz, CDCl3): 1.18 (s, 18H, C(CH3)3), 1.20
(s, 18H, C(CH3)3), 1.22 (s, 18H, C(CH3)3), 2.37–2.50 (m,
2H, OCH2CH2), 2.57–2.70 (m, 2H, OCH2CH2), 2.70–3.02
(m, 12H, OCH2 CH2), 3.03–3.12 (m, 2H, OCH2CH2), 3.25
(d, J = 13.5Hz, 2H, ArCH2Ar), 3.41–3.48 (m, 4H,
OCH2CH2), 3.52–3.62 (m, 2H, OCH2CH2), 3.73 (s, 2H,
OCH2Ar), 3.91 (d, J = 15.9 Hz, 2H, ArCH2Ar), 3.96 (s,
2H, OCH2Ar), 4.14 (d, J = 15.9 Hz, 2H, ArCH2Ar), 4.39
(d, J = 13.5 Hz, 2H, ArCH2Ar), 4.59 (d, J = 10.8 Hz, 2H,
ArCH2Ar), 4.83 (d, J = 10.8 Hz, 2H, ArCH2Ar), 6.87 (d,
J = 2.4 Hz, 2H, ArH), 6.98 (d, J = 2.4 Hz, 2H, ArH), 7.00
(d, J = 2.4 Hz, 2H, ArH), 7.12 (s, 4H, ArH), 7.22 (s, 10H,
ArH), 7.24 (d, J = 2.4 Hz, 2H, ArH). MS (ESI):
m/z = 1381.9 (M+). Anal. Calcd for C92H116O10: C,
79.96; H, 8.46. Found: C, 80.11; H, 8.55.
ethyl bromoacetate (0.042 g, 0.25 mmol) or benzyl bro-
mide (0.042 g, 0.25 mmol) wasadded and refluxed for
12 h. Then CH3CN wasremoved and the residue extracted
with 50 mL of CHCl3 and 50 mL of 10% HCl. The organic
phase was separated, washed twice with water (100 mL)
and the solvent was distilled off. The crude product was
subjected to recrystallization or chromatography to afford
pure productsasdecsribed below: Compound
3a was
obtained by recrystallization of the crude product from
CH2Cl2/MeOH (2:1. v/v) mixture in 65% (0.089 g) yield.
The mother liquid wasevaporated to drynessand the
residue was subjected to column chromatography on silica
gel using CHCl3 aseluent to afford 3b in 23% (0.032 g)
yield; 3a: mp > 270 ꢁC; 1H NMR (300 MHz, CDCl3): 1.16
(s, 18H, C(CH3)3), 1.22 (s, 18H, C(CH3)3), 1.25 (t,
J = 6.3 Hz, 6H), 1.36 (s, 18H, C(CH3)3), 2.52–2.63 (m,
2H, OCH2CH2), 2.88–3.28 (m, 12H, OCH2CH2), 3.29–
3.46 (m, 10H, OCH2CH2 and ArCH2Ar), 3.59 (d, 2H,
J = 16.5 Hz, ArCH2Ar), 3.63–3.72 (m, 2H, OCH2CH2),
3.91–4.05 (m, 4H, OCH2CH2 and ArCH2Ar), 4.07–4.22
(m, 6H, OCH2CH2, ArCH2Ar and OCH2CH3), 4.39 (s,
4H, OCH2CO), 4.75 (d, J = 14.4 Hz, 2H, ArCH2 AR),
6.74 (s, 2H, ArH), 6.96 (s, 2H, ArH), 7.06 (s, 2H, ArH),
7.12 (s, 2H, ArH), 7.17 (s, 2H, ArH), 7.24 (s, 2H, ArH);
MS (ESI): m/z = 1373.79 (M+). Anal. Calcd for
C86H116O14: C, 75.19; H, 8.51. Found: C, 75.33; H, 8.59;
3b: mp > 270 ꢁC; 1H NMR (300 MHz, CDCl3): 1.18 (s,
18H, C(CH3)3), 1.23 (t, J = 6.3 Hz, 6H), 1.26 (s, 18H,
C(CH3)3), 1.28 (s, 18H, C(CH3)3), 2.38–2.50 (m, 2H,
OCH2CH2), 2.64–2.75 (m, 2H, OCH2CH2), 2.84–2.96 (m,
2H, OCH2CH2), 2.97–3.07 (m, 2H, OCH2CH2), 3.09–3.40
(m, 10H, OCH2CH2 and ArCH2Ar), 3.54–3.79 (m, 6H,
OCH2CH2 and ArCH2Ar), 3.79–3.84 (m, 2H, OCH2CH2),
3.87–4.06 (m, 4H, OCH2CH2 and ArCH2Ar), 4.08–4.32
(m, 10H, OCH2CH2, ArCH2Ar and OCH2CH3), 4.49 (d,
J = 15.6 Hz, 2H, ArCH2Ar), 4.66 (d, J = 13.5 Hz, 2H,
ArCH2Ar), 6.91 (d, J = 2.4 Hz, 2H, ArH), 6.93 (d,
J = 2.4 Hz, 2H, ArH), 7.07 (d, J = 2.4 Hz, 2H, ArH),
7.11 (d, J = 2.4Hz, 2H, ArH), 7.23 (s, 4H, ArH). MS
(ESI): m/z = 1373.79 (M+). Anal. Calcd for C86H116O14:
C, 75.19; H, 8.51. Found: C, 75.41; H, 8.57; Compounds
4a and 4b were obtained by column chromatography of
the crude product on silica gel using CHCl3 aseluent. The
yieldswere 52% (0.071 g) and 34% (0.047 g), respectively.
12. Crystal data of 3a: C86H116O14, M = 1373.79, tetragonal,
space group P4(3)2(1)2, a = 13.1344(6), b = 13.1344(6),
˚
c = 47.415(3) A, a = 90, b = 90, c = 90ꢁ, V = 8179.7(7)
3
A , T = 293 K, Z = 4, l = 0.074 mmÀ1, R1 = 0.0875 for
˚
4404 F0 > 4r(F0) and 0.2712 for all 7628 data. CCDC No.
24420 contains the supplementary crystallographic data.
These data can be obtained free of charge from
www.ccdc.cam.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK. Fax: (internat.) +44
1223/336 033; E-mail: deposit@ccdc.cam.ac.uk].
13. Helgeson, R. C.; Weisman, G. R.; Toner, J. L.; Tarnow-
ski, T. L.; Chao, Y.; Mayer, J. M.; Cram, D. J. J. Am.
Chem. Soc. 1979, 101, 4928–4941.