Solvent-free synthesis of dihydroxy dithiacrown ethers

Article abstract of DOI:10.1016/j.tetlet.2010.12.045

The solvent-free reaction of oligoethylene glycol diglycidyl ethers with dimercaptoethane in the presence of benzyltrimethylammonium hydroxide (Triton B) gave, via regiospecific epoxide opening reactions, dihydroxy dithiacrown ethers in excellent yields and in short reaction times.

Full text of DOI:10.1016/j.tetlet.2010.12.045

Tetrahedron Letters 52 (2011) 881–883
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Solvent-free synthesis of dihydroxy dithiacrown ethers
Houcine Zoghlami a, Moufida Romdhani-Younes a, , Mohamed Moncef Chaabouni a,b, Ahmed Baklouti a
⇑
a Laboratoire de Chimie Organique Structurale, Département de Chimie, Faculté des Sciences de Tunis, Université Tunis El Manar, 2092 Tunis, Tunisia
b Ecole Supérieure des Industries Alimentaires, 58 Avenue Alain Savary, 1003 Tunis, Tunisia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2010
Revised 2 December 2010
Accepted 10 December 2010
Available online 17 December 2010
The solvent-free reaction of oligoethylene glycol diglycidyl ethers with dimercaptoethane in the presence
of benzyltrimethylammonium hydroxide (Triton B) gave, via regiospecific epoxide opening reactions,
dihydroxy dithiacrown ethers in excellent yields and in short reaction times.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Macrocycles
Dimercaptoethane
Thiacrown ethers
Diglycidyl ethers
Triton B
Solvent-free
The synthesis of macrocyclic molecules containing mixed O,S-
donors has been developed substantially over recent years.1 These
macrocycles have been used as selective extractants for soft metal
cations2,3 including silver(I)4 and copper(I).5 On the other hand,
thiacrown ethers having two or more functional groups are partic-
ularly interesting because of their potential application in the syn-
thesis of bicyclic compounds.6 Some work in this area has been
devoted to the synthesis of functionalized thiacrown ethers.7 To
our knowledge, these reactions were carried using an excess of sol-
vent and gave low yields. Solvent-free organic reactions are impor-
tant from the viewpoint of green and sustainable chemistry.8
We present here a simple and solvent-free synthesis of sym-
metrical dihydroxy dithiacrown ethers from diglycidyl ethers and
dimercaptoethane under mild conditions and in short reaction
times.
good yields (Table 1). The yields are given for the products isolated
after chromatography.
In all cases, the bis-epoxides were opened regiospecifically by
intermolecular nucleophilic attack on the terminal carbon atoms
affording symmetrical dihydroxy dithiacrown ethers 2a–d. The
macrocyclization was achieved without solvent under mild condi-
tions at room temperature. We note that the longer the chain of the
diglycidyl ether, the easier and more efficient the reaction. With
compounds 1b–d, the reaction was complete after 30 min at
25 °C. In the case of compound 1a, the reaction was highly exother-
mic and was, therefore, run at 0 °C.
According to the reaction procedure, addition of dimercaptoe-
thane was carried out dropwise over 30 min. Under these condi-
tions, and in spite of the absence of solvent, the bis-epoxide is in
large excess compared to dimercaptoethane (i.e., high dilution con-
ditions). This may prevent polymerization which requires stoichi-
ometric quantities of each monomer.
It should be noted that as the epichlorohydrin used is a racemic
mixture, the bis-epoxides 1a–d and the dihydroxy dithiacrown
ethers 2a–d exist as mixtures of diastereoisomers. However, in
each case, the two stereogenic centers within the molecule are dis-
tant from each other such that diastereoisomers could not be dis-
cerned by NMR spectroscopic techniques. The 1H NMR spectra of
the diastereoisomeric mixtures show the presence of a sharp sin-
glet for the two methylene groups of the dimercaptoethane
moiety.
In a previous Letter,9 we reported the ring-opening reaction of
alkyl oxiranes with dimercaptoethane. In the same context, we
have developed the synthesis of new dihydroxy dithiacrown ethers
1a–d from oligoethylene glycol diglycidyl ethers which are
themselves prepared by reaction of epichlorohydrin with polyoxy-
ethylene under phase-transfer catalysis conditions in basic
medium10 (Scheme 1).
Nucleophilic opening of diglycidyl ethers 1a–d by dimercaptoe-
thane in the presence of Triton B as the phase-transfer catalyst11
(Scheme 2) afforded dihydroxy dithiacrown ethers 2a–d in very
In conclusion, this Letter describes an efficient method for the
synthesis of symmetrical dihydroxy dithiacrown ethers under sol-
vent-free conditions. Bis-epoxides were opened regiospecifically
⇑
Corresponding author. Fax: +216 72590566.
E-mail address: moufida.romdhani@gmail.com (M. Romdhani-Younes).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.12.045

882
H. Zoghlami et al. / Tetrahedron Letters 52 (2011) 881–883
Cl
NaOH
PTC
O
H
O
O
n
O
H
+
n
O
O
O
n = 1-4
n = 1-4
1a-d
Scheme 1.
Triton B
30 min
O
O
O
O
n
O
HO
OH
+
O
n
HS
SH
O
O
n = 1-4
1a-d
n = 1-4
2a-d
Scheme 2.
Table 1
Ring-opening of diglycidyl ethers by dimercaptoethane
Diglycidyl ether
Dihydroxy dithiacrown ether
Yield (%)
O
O
O
O
S
O
S
O
HO
OH
1a
90
2a
O
O
O
2
O
O
O
O
1b
94
S
OH
S
HO
2b
O
O
O
O
3
O
O
1c
O
O
98
S
S
HO
OH
2c
O
O
O
4
O
O
O
O
1d
O
O
96
S
S
OH
HO
2d
Tetrahedron 2007, 63, 5220; (e) Alfimov, M. V.; Fedorov, Y. V.; Fedorova, O. A.;
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S. M.; Sandarooss, R. Chin. Chem. Lett. 2007, 18, 1439.
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the terminal carbon atoms. The reaction products may prove useful
in synthesis, particularly for bicyclic compounds.
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