A facile method for synthesis of calix[4]crowns containing nitrogen and sulfur atoms

Article abstract of DOI:10.1039/a808527g

A synthesis of calix[4]crowns containing nitrogen and sulfur atoms and bischloroacetamides is reported.

Full text of DOI:10.1039/a808527g

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212 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
A Facile Method for Synthesis of Calix[4]crowns
1999, 212^213y
Containing Nitrogen and Sulfur Atomsy
Qi-Yu Zheng, Chuan-Feng Chen and Zhi-Tang Huang*
Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100080, China
A synthesis of calix[4]crowns containing nitrogen and sulfur atoms and bischloroacetamides is reported.
Calixarenes are important molecular building blocks for the
synthesis of new receptors for `catching' ions and/or neutral
molecules in supramolecular chemistry. Calixcrowns, con-
presence of K2CO3 and KI in acetone^toluene; the yields
ranged from 27 to 47% (Scheme 2).
1
structed by introducing a polyether chain into the lower
rim of calixarenes, have been shown to be very e¤cient
ionophores for hard ions, such as alkali and alkaline earth
metals, and to possess superior ion selectivity and high a¤n-
ity because of the preorganization e¡ect arising from the
R
R
R
R
R
K2CO3/Kl
2�4
O
O
calixarene ring.
To increase the complexation capability
+ 4a–c
OH OH
NH HN
acetone/toluene
reflux
of the receptor to `soft ions', the incorporation of
heteroatoms, such as nitrogen or sulfur atoms, into
CH2
O
O
OH
5;6
4
macrocycles has proved e¤cient.
However, calixcrowns
S
S
containing heteroatoms have been studied only to a small
extent and calixcrowns containing both nitrogen and sulfur
atoms have, as yet, not been reported. We report herein, a
facile method for the synthesis of calix[4]crowns, containing
both nitrogen and sulfur atoms.
R = But
X
5
6
R = H
7–10
7
8
9
But
10
But
R
X
But
H
Methods for synthesis of calix[4](aza)crowns containing
7� 9
H2C
N
CH2
amide or imine groups (Schi¡ bases) have been reported.
CH2CH2 CH2CH2 CH2CH2CH2
They utilized the condensation of distal diesters or acid
chlorides of calix[4]arenes with diamines to synthesize
calix(aza)crowns containing amide groups in the crown ether
subcycles. However, this method requires several steps
starting from calix[4]arenes. Here, we use a simple method
to synthesize calixcrowns containing both nitrogen and sulfur
atoms. It requires only one step starting from calix[4]arenes
and another easily prepared reactant, a bischloroacetamide.
Bischloroacetamides 4 were synthesized by the reaction of
chloroacetyl chloride with diamines 3, which can be obtained
from 2-aminoethanethiol hydrochloride and dibromides 2
Scheme 2
Products 7^10 were characterized by 1H and 13C NMR
spectroscopy, FAB-MS, IR and elemental analysis. In the
H NMR spectra of calix[4]crowns 7^10, the signal of the
methylene protons between aromatic rings showed a typical
1
1
3
AB pattern ꢀJ ˆ 13:0 Hz), whilst in the C NMR spectra
of 7^10, there was only one corresponding methylene signal
(
Scheme 1).
ꢀ
d ꢁ 31). This demonstrates that these calix[4]crowns exist
in cone conformations and that the molecules are in high
symmetry.
H2NCH2CH2SH • HCl
+
Br–X–Br
1
2a–c
i. NaHCO3 ii. HCl / EtOH
H2NCH2CH2S–X–SCH2CH2NH2 • 2HCl
a–c
Experimental
3
Mps are uncorrected. H and 13C NMR spectra were recorded on a
Varian Unity 200 spectrometer with CDCl3 as solvent and TMS as
internal reference. IR spectra were recorded with a Perkin-Elmer
782 spectrometer. Mass spectra were recorded on a KYKY-ZHT-5
instrument. Elemental analyses were performed by the Analytical Lab-
1
SCH2CH2NH2
SCH2CH2NHCOCH2Cl
Na2CO3
X
• 2HCl + ClCH2COCl
X
SCH2CH2NH2
SCH2CH2NHCOCH2Cl
4a–c
10
oratory of the institute. p-tert-Butylcalix[4]arene 5 and calix[4]arene
11
a
b
c
6
were prepared according to literature procedures.
General Procedure for the Preparation of Bischloroacetamides 4.öA
solution of dibromides 2 (35 mmol) in ethanol (60 ml) was added
dropwise under nitrogen atmosphere to solution of
-aminoethanethiol hydrochloride (70 mmol) and NaHCO3
70 mmol) in water (130 ml). The mixture was stirred at room tem-
H2C
N
CH2
X
CH2CH2
CH2CH2CH2
a
a
2
(
perature for 30 min and re£uxed for 3 h, and then concentrated
in vacuo. The residue was treated with ethanol and hydrochloric acid,
and cooled in an ice bath to obtain a precipitate. After ¢ltering this
o¡ and washing with anhydrous ethanol (40 ml), the product 3
was dissolved in water (20 ml) and the pH of solution was adjusted
to 7 by addition of a saturated aqueous solution of K2CO3. Then
CHCl3 (30 ml) was added and chloroacetyl chloride (70 mmol) in
chloroform (70 ml) and K2CO3 (35 mmol) in water (250 ml) were
added separately through dropping funnels to the above stirred sol-
Scheme 1
Calix[4]crowns 7^10 containing nitrogen and sulfur atoms
were readily synthesized by the reaction of
p-tert-butylcalix[4]arene 5 or calix[4]arene 6 with 4 in the
ꢂ
*
To receive any correspondence.
ution at 0^5 C over 3 h. The mixture was stirred for an additional
yThis is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).
3 h at room temperature. The organic phase was separated and
washed several times with water. After removal of solvent in vacuo,
the product was crystallized from ethanol in an ice bath.

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J. CHEM. RESEARCH (S), 1999 213
1
,8-Bis(chloroacetamido)-3,6-dithiaoctane (4a). Yield 69%; mp
4.53 (s, 4 H, ArOCH2), 6.55 (s, 2 H, OH), 6.74 (s, 4 H, ArH), 7.10 (s,
4 H, ArH), 7.98 (br, 2 H, NH); dC ꢀCDCl3† 29.37, 30.33, 30.81, 30.92,
31.55, 32.09, 33.86, 34.07, 38.95, 74.80, 125.58, 126.16, 127.23, 132.34,
ꢂ
1
16^118 C (ethanol). (CDCl3) 2.73 (t, 4 H, NHCH2CH2S†, 2.77 (s,
H, SCH2CH2S), 3.55 (q, 4 H, NHCH2†, 4.06 (s, 4 H, ClCH2CO),
.07 (br, 2 H, NH).
4
‡
7
143.10, 148.31, 149.04, 149.34, 168.30. FAB-MS: m/z 921ꢀ‰M � 1Š †.
1
,9-Bis(chloroacetamido)-3,7-dithianonane (4b). Yield 30%; mp
Anal. Calc. for C55H74N2O6S2 : C, 71.54, H, 8.08, N, 3.03. Found:
ꢂ
6
(
3^64 C (ethanol). dH (CDCl3) 1.90 (qnt, 2 H, CH2CH2CH2†, 2.66
C, 71.29, H, 8.11, N, 3.01%.
0
t, 4 H, NHCH2CH2S†, 2.73 (t, 4 H, SCH2CH2CH2S†, 3.52 (q, 4 H,
2,6-[4 -(5,11,17,23-tetra-tert-Butyl-25,27-dihydroxycalix[4]arene-
0
NHCH2†, 4.08 (s, 4 H, ClCH2CO), 7.04 (br, 2 H, NH).
26,28-diyl)bis(oxyacetamido-2 -thiabutyl )]pyridine (10). Reaction time
0
0
ꢂ
� 1
2
,6-Bis(4 -chloroacetamido-2 -thiabutyl ) pyridine (4c). Yield 30%;
48 h; yield 27%; mp 150^152 C ꢀCHCl3 ^CH3OH). IR (nmax=cm ):
ꢂ
mp 65^66 C (ethanol). dH ꢀCDCl3, 2.69 (t, 4 H, NHCH2CH2S†, 3.52
3365 (NH), 1680 (CO), 1540, 1485. dH ꢀCDCl † 1.05 [s, 18 H,
3
(
7
q, 4 H, NHCH2†, 3.89 (s, 4 H, SCH2Py†, 4.05 (s, 4 H, ClCH2CO†,
.24 (br, 2 H, NH), 7.31 (d, 2 H, PyH), 7.72 (t, 1H, PyH).
General procedure for the preparation of aza- and thia-
calix[4]crowns 7^10.öTo solution of bischloroacetamides
2.5 mmol) and p-tert-butylcalix[4]arene 5 or calix[4]arene 6 (2 mmol)
CꢀCH3† ] 1.29 [s, 18 H, CꢀCH3† Š, 2.77 (t, 4 H, NHCH2CH2S†, 3.43
3
3
(d, 4 H, JAB 13.0, ArCH2Ar†, 3.48 (s, 4 H, NHCH2), 3.93 (s, 4 H,
SCH2Py†, 4.15 (d, 4 H, JAB 13.0, ArCH2Ar), 4.56 (s, 4 H,
ArOCH2†, 6.90 (s, 4 H, ArH), 7.10 (s, 4 H, ArH), 7.29 (d, 2 H, PyH,
7.71 (t, 1 H, PyH), 7.67 (s, 2 H, OH), 8.87 (br, 2 H, NH);
dC ꢀCDCl3† 29.86, 30.89, 31.54, 32.13, 33.87, 34.04, 37.34, 39.62, 74.78,
121.51, 125.57, 126.17, 127.37, 132.21, 138.19, 143.34, 148.31, 149.22, 149.30,
a
4
(
in acetone (50 ml)^toluene (20 ml) were added K2CO3 (2 mmol) and
KI (4 mmol). After the reaction mixture was stirred under re£ux
for 12^48 h, the solvent was removed in vacuo and the residue
was dissolved in 0.2 M HCl (50 ml) and CHCl3 (50 ml). The organic
layer was washed with water, concentrated and then
chromatographed on a silica gel column using CHCl3 ^petroleum
‡
158.23, 167.82. FAB-MS: m/z 984ꢀ‰M � 1Š †. Anal. Calc. for
C59H75N3O6S2: C, 71.84, H, 7.66, N, 4.26; Found: C, 71.58, H, 7.61,
N, 4.48 %.
ꢂ
ether (bp 60^90 C) (2 :1 v/v) as eluent to a¡ord a white solid which
was recrystallized from CHCl3 ^CH3OH to give pure compounds
This work was supported by the National Natural Science
Foundation of China.
7
^10.
1
,8-[(5,11,17,23-tetra-tert-Butyl-25,27-dihydroxycalix[4]arene-26,28-
diyl )bis(oxyacetamido)]-3,6-dithiaoctane (7). Reaction time 12 h; yield
Received, 3rd November 1998; Accepted, 30th November 1998
Paper E/8/08527G
ꢂ
� 1
3
1
3%; mp 175 C (decomp.) ꢀCHCl3^CH3OH†: IR (n=cm ): 3370 (NH),
670 (CO), 1540, 1495. dH ꢀCDCl3† 0.92 [s, 18 H, CꢀCH3† ], 1.31 [s, 18 H,
3
CꢀCH3† ], 2.84 (s, 4 H, SCH2CH2S†, 2.85 (t, 4 H, NHCH2CH2S†, 3.38
3
(
d, 4 H, JAB 13.0, ArCH2Ar), 3.65 (q, 4 H, NHCH2), 4.20 (d, 4 H,
References
JAB 13.0, ArCH2Ar†, 4.52 (s, 4 H, ArOCH2†, 6.72 (s, 2 H, OH), 6.76
s, 4 H, ArH), 7.10 (s, 4 H, ArH), 8.03 (br, 2 H, NH); dC ꢀCDCl3† 30.82,
0.84, 31.61, 31.72, 32.32, 33.87, 33.89, 39.79, 74.25, 125.35, 125.90, 127.74,
(
1 For recent review, see: A. Ikeda and S. Shinkai, Chem. Rev.,
1997, 97, 1713.
2 H. Yamamoto, T. Sakaki and S. Shinkai, Chem. Lett., 1994,
469.
3 A. Casnati, A. Pochini, R. Ungaro, F. Ugozzoli, F. Arnaud, S.
Fanni, M.-J. Schwing, R. J. M. Egberink, F. de Jong and
D. N. Reinhoudt, J. Am. Chen. Soc., 1995, 117, 2767.
4 A. Casnati, A. Pochini, R. Ungaro, S. Bocchi, F. Ugozzoli, R. J.
M. Egberink, H. Struijk, R. Lugtenberg, F. de Jong and D. N.
Reinhoudt, Chem. Eur. J., 1996, 2, 436.
5 A. T. Yordanov, J. T. Mague and D. M. Roundhill, Inorg.
Chem., 1995, 34, 5084.
6 A. T. Yordanov, J. T. Mague and D. M. Roundhill, Inorg.
Chim. Acta, 1995, 240, 441.
7 V. Boehmer, G. Ferguson, J. F. Gallagher, A. J. Lough, M. A.
McKervey, E. Madigan, M. B. Moran and J. Phillips, J. Chem.
Soc., Perkin Trans. 1, 1993, 1521.
3
1
31.88, 142.65, 147.79, 149.71, 149.76, 169.07. FAB-MS: m/z 907
‡
ꢀ
‰M � 1Š †. Anal. Calc. for C54H72N2O6S2 : C, 71.33, H, 7.98, N, 3.08.
Found: C, 70.81, H, 7.89, N, 3.43%.
1
,8-[(25,27-Dihydroxycalix[4]arene-26,28-diyl)bis(oxyacetamido)]3,6-
ꢂ
dithiaoctane (8). Reaction time 48 h; yield 44%; mp 270 C (decomp.)
�
1
ꢀ
CHCl3^CH3OH†. IR ꢀn=cm †: 3350 (NH), 1665, (CO), 1540, 1465.
dH ꢀCDCl3† 2.84 (t, 4 H, NHCH2CH2S†, 2.85 (s, 4 H, SCH2CH2S†,
.44 (d, 4 H, JAB 13.0, ArCH2Ar†, 3.71 (q, 4 H, NHCH2†, 4.25 (d,
H, JAB 13.0, ArCH2Ar), 4.55 (s, 4 H, ArOCH2†, 6.73 (t, 2 H, ArH),
.78 (t, 2 H, ArH), 6.89 (d, 4 H, ArH), 7.10 (d, 4 H, ArH), 7.53 (s,
H, OH), 7.74 (br, 2 H, NH); dC ꢀCDCl3† 30.75, 31.42, 32.15, 39,75,
3
4
6
2
7
4.35, 119.84, 126.05, 127.71, 128.80, 129.37, 132.62, 151.84, 152.52, 168.51.
‡
FAB -MS : m/z 683 ꢀ‰M � 1Š †. Anal. Calc. for C38H40N2O6S2 : C,
6
6.64, H, 5.89, N, 4.09. Found: C, 65.89, H, 5.82, N, 4.04%.
1
,9-[(5,11,17,23-tetra-tert-Butyl-25,27-dihydroxycalix[4]arene-26,28-
diyl)bis(oxyacetamido)]-3,7-dithianonane (9). Reaction time 48 h;
8 I. Bitter, A. Gru
«
¬
n, G. Toth, B. Balazs and L. Toke,
¨ ¨
ꢂ
� 1
yield 47%; mp 215^216 C ꢀCHCl3 ^CH3OH†. IR ꢀn=cm ): 3370
Tetrahedron, 1997, 53, 9799.
(
NH), 1670 (CO), 1540, 1490. dH ꢀCDCl3† 0.91 [s, 18 H, CꢀCH3† Š,
9 R. Seangprasertkij, Z. Asfari, F. Arnaud and J. Vicens, J. Org.
Chem., 1994, 59, 1741.
10 C. D. Gutsche, Org. Synth., 1989, 68, 234.
11 C. D. Gutsche and L.-G. Lin, Tetrahedron, 1986, 42, 1633.
3
1
.31 [s, 18 H, CꢀCH3† Š, 1.92 (qnt, 2 H, CH2CH2CH2†, 2.73 (t,
3
4
H, NHCH2CH2S†, 2.83 (t, 4 H, SCH2CH2S†, 3.38 (d, 4 H, JAB 13.0,
ArCH2Ar), 3.69 (q, 4 H, NHCH2†, 4.20 (d, 4 H, JAB 13.0, ArCH2Ar†,