Synthesis, separation and characterization of thiacalix[4]arenes diastereomers

Article abstract of DOI:10.1080/10426500701564183

Two different 1, 3-Distal thiacalix[4]arenas were prepared by the reaction of thiacalix[4]arene with phenacyl and/or p-nitro phenacyl bromide in acetone or acetonitrile in the presence of dry CsOH. The prepared 1, 3-distal disubstituted thiacalixarenes afforded two pairs of diastereomers upon brominating in chloroform. The obtained diastereomers were separated by fractional crystallization in a mixture dichloromethane-acetone.

Full text of DOI:10.1080/10426500701564183

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Phosphorus, Sulfur, and Silicon
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Synthesis, Separation
and Characterization
of Thiacalix[4]arenes
Diastereomers
Omran Abdellah Omran a , Kim Larsen b , Reinhard
Wimmer b & Donghong Yu b
a Chemistry Department, Faculty of Science , Sohag
University , Sohag, Egypt
b Department of Biotechnology, Chemistry and
Environmental Engineering , Aalborg University ,
Aalborg, Denmark
Published online: 20 Feb 2008.
To cite this article: Omran Abdellah Omran , Kim Larsen , Reinhard Wimmer &
Donghong Yu (2007) Synthesis, Separation and Characterization of Thiacalix[4]arenes
Diastereomers, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:1,
150-155, DOI: 10.1080/10426500701564183
To link to this article: http://dx.doi.org/10.1080/10426500701564183
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Phosphorus, Sulfur, and Silicon, 183:150–155, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701564183
Synthesis, Separation and Characterization
of Thiacalix[4]arenes Diastereomers
Omran Abdellah Omran,1 Kim Larsen,2
Reinhard Wimmer,2 and Donghong Yu2
1Chemistry Department, Faculty of Science, Sohag University,
Sohag, Egypt
2Department of Biotechnology, Chemistry and Environmental
Engineering, Aalborg University, Aalborg, Denmark
Two different 1, 3-Distal thiacalix[4]arenas were prepared by the reaction of thia-
calix[4]arene with phenacyl and/or p-nitro phenacyl bromide in acetone or acetoni-
trile in the presence of dry CsOH. The prepared 1, 3-distal disubstituted thiacal-
ixarenes afforded two pairs of diastereomers upon brominating in chloroform. The
obtained diastereomers were separated by fractional crystallization in a mixture
dichloromethane-acetone.
Keywords Bromination; diastereomers; separation; thiacalixarene
INTRODUCTION
Calix[n]arenes—three-dimensional structural compounds—are for
many reasons considered one of the most important synthetic construc-
tion units in molecular recognition and supramolecular chemistry.1 Ap-
plications of calixarenes range from highly specific ligands in analyt-
ical chemistry and medical diagnostic systems to the construction of
artificial enzymes and non-linear optics.2 Thiacalixarenes,3 a new cal-
ixarenes family, are easily prepared from the condensation reaction of
p-alkylphenol and elemental sulfur under basic conditions. Because of
the replacement of methylene groups in classical calixarenes by sulfur
atoms in thiacalixarenes, the latter systems have many novel features
and represent very promising building blocks and molecular scaffolds
Received 17 May 2007; accepted 29 June 2007.
This work was supported by the Bibliotheca Alexandrina-Center for special studies
and programs under Grant No. (04041083).
Address correspondence to Omran Abdellah Omran, Chemistry Department, Faculty
of Science, Sohag University, Sohag 82524, Egypt. E-mail: omran2002@mailcity.com
150

Thiacalix[4]arenes Diastereomers
151
for the synthesis of more complicated supramolecular systems. Only a
limited number of methods for the synthesis of chiral thiacalixarenes4
are currently known.
As part of our efforts to generate new chiral thiacalixarenes for enan-
tiomeric discrimination, we here report the synthesis, characterization,
and separation of four thiacalixarenes diastereomers.
RESULTS AND DISCUSSION
1,3-Distal disubstituted thiacalixarene 4 have been isolated as side
products in our previous work5 with a low yield by the reaction of thi-
acalixarenes 1 with phenacyl bromide 2 in acetonitrile in the presence
of Cs2CO3 as a catalyst. The method has been modified to increase the
yield of compound 4 to 80% by changing the base, as well as the molec-
ular ratio of the reactants, where in place of Cs2CO3, CsOH was used
with stoichiometry 1:2:2, respectively.
The same reaction was repeated using p-nitrophenacyl bromide
3 to prepare 1,3-distal disubstituted thiacalixarenes 5 in 75% yield
(Scheme 1).
1
The structures of the obtained compounds were confirmed by H-
NMR, MALDI-TOF-MS spectroscopy. As reported by Iki et al., the use
of Cs metal as a catalyst would lead to products of 1,3-distal substituted
SCHEME 1 Synthesis and separation of two pairs of diastereomers.

152
O. A. Omran et al.
thiacalixarene.6 The 1H-NMR spectra of compounds 4 and 5 were found
to be similar for the t-Bu-H, Ar-H and -OCH2-CO- peaks, and for Ph-H
where 4 shows three different peaks one for o-Ph-H, other for m-Ph-H
and the third for p-Ph-H, on the other hand compound 5 shows two
doublets. Bromination of the two active methylene groups in thiacal-
ixarenes 4,5 (Br2, 2 equiv. in chloroform) produced two pairs of chiral
thiacalixarenes 6a, 6b, 7a, and 7b in 90% (for the mixture of 6a and
6b) and 88% (for the mixture of 7a and 7b) yield respectively. The
separation of the two different diastereomers 6a, 6b and 7a, 7b were
based on the fractional crystallization of the crude 6 and/or 7 from
dichloromethane-acetone mixture. The NMR spectra of 1,3-distal 4,5
showed the Ar-H protons as two singlets where those protons appeared
as four doublets in 6a, 7a, and eight doublets in 6b, 7b, respectively (cf.
Fig. 1).
EXPERIMENTAL
All NMR spectra were recorded on a BRUKER DRX600 NMR spec-
trometer equipped with a triple-gradient TXI (H/C/N) probe operating
at a magnetic field strength of 14.1 T. Mass spectrometric analysis
was carried out on a MALDI-TOF-MS REFLEX III (Bruker-Daltonics,
Germany).
1, 3-Distal Disubstituted Thiacalixarenes 4 and 5—General
Procedure
Thiacalixarene 1 (1.00 g, 1.4 mmol) was suspended in dry acetoni-
trile or acetone-containing melting dried CsOH (0.41 g , 2.8 mmol)
and phenacyl bromide (0.55 g, 2.8 mmol) or p-nitro-phenacyl bromide
(0.68 g, 2.8 mmol). The reaction mixtures were refluxed for 24 h; after
cooling, the reaction mixture was treated in two different ways: in case
of phenacyl bromide the product 4 was separated from the solid layer;
and in case of the p-nitro phenacyl bromide the product 5 was separated
from the filtrate layer.
Compound 4
1H (400 MHz, CDCl3, 25◦C): δ (ppm): 0.81 (s, 18H, 2 But); 1.32(s,
18H, 2 But); 6.17 (s, 4H, 2 OCH2CO ); 6.95 (s, 4H, Ar-H); 7.48 (t, 4H,
m-Ph-H, J= 7.9 );7.59 (t, 2H, p-Ph-H, J=7.9 ); 7.67 (s, 4H, Ar-H); 8.16
(d, 4H, o-Ph-H, J= 7.9); 8.35 (s, 2H, OH)., IR, (KBr, v/cm−1)3395, 3366
cm−1 (OH), 1699 cm−1, (OH); M.P. 241–242◦C m/z 957 (MH+).
Compound 5
1H (400 MHz, CDCl3, 25◦C):δ (ppm): 0.80 (s, 18H, 2 But); 1.35(s, 18H,
2 But); 6.20 (s, 4H, 2 -OCH2CO-); 6.95 (s, 4H, Ar-H); 7.7 (s, 4H, Ar-H);

Thiacalix[4]arenes Diastereomers
153
FIGURE 1 (a) 1H-NMR Spectra of Compound 4; (b) 1H-NMR Spectra of Com-
pound 6a; (c) 1H-NMR Spectra of Compound 6b.

154
O. A. Omran et al.
8.12 (s, 2H, OH). 8.35 (d, 4H, o-Ph-H); 8.40 (d, 4H, m-Ph-H, J = 9.5).
M.P.170◦C; m/z 1047 (MH+).
Bromination of 1,3-Distal Disubstituted Thiacalixarenes
4, 5—General Procedure
A solution of bromine in 5 ml of CHCl3 was added dropwise to a solution
of 0.5 g of compound 4 and/or 5 in 20 ml CHCl3 in 30 min. The bromine
color disappeared during the addition. The reaction mixture was stirred
for further 30 min. The chloroform layer was evaporated in vacuo. The
crude solid was recrystallized from dichloromethane-acetone into 6a
and 6b as first and second fractions from 4; 7a and 7b diastereomers
as first and second fractions from 5.
Compound 6a
1H (400 MHz, CDCl3, 25◦C): δ (ppm): 1.1 (s, 18H, But); 1.30(s,18H,
But); 7.47 (t, 4H, m-Ph H, J = 7.9 ); 7.48 (d, 2H, Ar-H, J = 4 ); 7.53 (d,
2H, Ar-H, J= 4 ) 7.62 (t, 2H, p-Ph-H, J = 7.9); 7.64(d, 2H, Ar-H, J = 4
); 7.66 (d, 2H, Ar-H, J = 4 ); 7.95 (d, 4H, o-Ph-H, J = 7.9 ); 8.22 (s, 2H,
CHBrCO-,); 8.7 (s, 2H, OH). M.P. 200◦C (decomp.).; m/z 1117 (MH+).
Compound 6b
1H (400 MHz, CDCl3, 25◦C): δ (ppm): 1.1 (s, 18H, But); 1.30 (s, 18H,
But); 7.07 (d, 1H, Ar-H, J = 1.5 ); 7.1 (d, 1H, Ar-H, J = 1.5); 7.45(t, 4H,
m = Ph-H, J = 7.9 ); 7.48 (d, 1H, Ar-H, J = 2); 7.51 (d, 1H, Ar-H, J =
2); 7.52 (d, 1H, Ar-H, J = 2); 7.59 (t, 2H, p-Ph-H, J = 7.9 ); 7.61(d, 1H,
Ar-H, J = 2); 7.62 (d, 1H, Ar-H, J = 2);7.64 (d, 1H, Ar-H, J = 2 ); 7.94 (d,
4H, o-Ph-H, J = 7.9 ); 8.20 (s, 2H, CHBrCO- ); 8.71(s, 2H, OH). M.P.
190◦C (decomp.); m/z 1117 (MH+).
Compound 7a
1H (400 MHz, CDCl3, 25◦C): δ (ppm): 1.05 (s, 18H, But); 1.25(s, 18H,
But); 7.33 (s, 2H, CHBrCO-,); 7.38 (d, 2H, Ar-H, J = 2);7.43 (d, 2H,
Ar-H, J = 2) 7.61 (d, 2H, Ar-H, J = 2 ); 7.71 (d, 2H, Ar-H, J = 2); 8.7
(s,2H, OH); 8.37 (d, 4H, m-Ph-H,J = 6.9); 8.39 (d, 4H, o-Ph-H, J = 6.9).
M.P. 190◦C (decomp.).; m/z 1207 (MH+).
Compound 7b
1H (400 MHz, CDCl3, 25◦C): δ (ppm):. 0.70 (s, 18H, But); 1.20(s, 18H,
But); 6.91 (d, 1H, Ar-H, J = 1.9 ); 6.93 (d, 1H, Ar-H, J = 1.9 ); 7.52 (d,
2H, Ar-H, J = 1.9);7.54 (d, 2H, Ar-H, J = 1.9) 7.64 (d, 2H, Ar-H,J = 1.9);
7.65 (s, 2H, CHBrCO ); 7.66 (d, 2H, Ar-H, J = 1.9); 7.69 (d, 2H, Ar-H,
J = 1.9);7.71 (d, 2H, Ar-H, J = 1.9 ); 7.42 (d, 4H, m Ph H, J = 6.9);

Thiacalix[4]arenes Diastereomers
155
8.58 (d, 4H, o-Ph-H, J = 6.9). 8.66 (s, 2H, OH). M.P. 136◦C ; m/z 1207
(MH+).
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