An alternative approach towards the syntheses of thioethers and thioesters using CsF-Celite in acetonitrile

Article abstract of DOI:10.1016/S0040-4039(02)02028-2

It has been found that syntheses of thioethers and thioesters of aliphatic, aromatic and heterocyclic compounds, bearing thiol groups, can be accomplished with alkyl, acyl, benzyl or benzoyl halides in acetonitrile and cesium fluoride-Celite. In this manner, compounds like ethanethiol, 1-pentanethiol, thiophenol, 4-methoxythiophenol, 4-nitrothiophenol, and 2-mercaptobenzoxazole, 2-mercaptobenzothiazole, and 2-mercapto-2-thiazoline can be successfully alkylated, acylated, benzylated or benzoylated. This procedure is convenient, efficient and practical for the preparation of thioethers and thioesters.

Full text of DOI:10.1016/S0040-4039(02)02028-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8281–8283
An alternative approach towards the syntheses of thioethers and
thioesters using CsF–Celite in acetonitrile†
Syed Tasadaque Ali Shah,a Khalid Mohammed Khan,b Angelica Martinez Heinricha and
Wolfgang Voeltera,*
aAbteilung fu¨r Physikalische Biochemie des Physiologisch-chemischen Instituts der Universita¨t, Tu¨bingen, Hoppe-Seyler Straße 4,
D-72076 Tu¨bingen, Germany
bHEJ Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi-75270,
Pakistan
Received 20 August 2002; accepted 16 September 2002
Abstract—It has been found that syntheses of thioethers and thioesters of aliphatic, aromatic and heterocyclic compounds, bearing
thiol groups, can be accomplished with alkyl, acyl, benzyl or benzoyl halides in acetonitrile and cesium fluoride–Celite. In this
manner, compounds like ethanethiol, 1-pentanethiol, thiophenol, 4-methoxythiophenol, 4-nitrothiophenol, and 2-mercaptobenz-
oxazole, 2-mercaptobenzothiazole, and 2-mercapto-2-thiazoline can be successfully alkylated, acylated, benzylated or benzoylated.
This procedure is convenient, efficient and practical for the preparation of thioethers and thioesters. © 2002 Elsevier Science Ltd.
All rights reserved.
Protection of thiol groups is important in many areas
of organic research, particularly in peptide, protein and
b-lactam synthesis.1,2a A free SH group can be pro-
tected as thioether, thioester or, after oxidation, as
disulfide, from which it can be regenerated by reduc-
tion. Thioethers are, in general, formed by reaction of
thiols or thiophenols under basic conditions with alkyl
or benzyl halides. Thioesters are formed and cleaved in
the same way as oxygen esters; they are more reactive
against nucleophilic substitution2b and used as ‘acti-
vated esters’.
transfer reactions,10 organometallic sulfides,11 montmo-
rillonite clay catalysis12 and trifluoroacetic acid.13
Recently, Yin and Pidgeon14 reported a high yield
method for the preparation of unsymmetrical sulfides
by using very strong basic n-butyllithium.
In continuation of our interest in developing new
organic synthetic methodologies,15 we reported very
recently the N-alkylation16 of amines using CsF–Celite
as a solid base. In extension of our work on the
reactivity of CsF–Celite, we wish to report the utility of
CsF–Celite for the synthesis of thioethers and thioesters
in good yields (Scheme 1).
The conversion of thiols to thioethers is usually
achieved by reaction of thiolate with organic halides.3
The yields and reaction conditions depend on the sol-
vent, the basic catalyst and the acidity of thiol. These
reactions require very long refluxing time and yields
obtained were low.4
The CsF–Celite-assisted coupling of aliphatic and aro-
matic thiols with various alkyl, acyl, benzyl and ben-
zoyl halides resulted in thioethers and thioesters (Tables
1 and 2).
Several other methods were employed for preparing
thioethers which include palladium(0)-mediated alkyla-
tion,5 phase transfer catalysis,6 platinum(II) complex
with bis(diphenylphosphino)methane,7 bis(diphenyl-
stannyl)telluride,8 tin sulfides with aryl halides,9 ligand
In a typical reaction, to a mixture of thiol (1.0 mol) and
CsF–Celite (1.5 mol) in 20 ml of acetonitrile, alkyl,
* Corresponding
author.
Fax:
+497071-293348;
e-mail:
wolfgang.voelter@uni-tuebingen.de
Dedicated to Professor Atta-ur-Rahman on the occasion of his 60th
birthday.
†
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02028-2

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S. T. A. Shah et al. / Tetrahedron Letters 43 (2002) 8281–8283
Table 1. Synthesis of thioethers using CsF–Celite
Table 2. Synthesis of thioesters using CsF–Celite
acyl, benzyl, or benzoyl halides (2.0 mol) were added.
Then, the mixture was stirred at room temperature or
refluxed up to completion of the reaction, indicated by
TLC monitoring. The reaction mixture was filtered and
the solvent evaporated. The product was purified,
whenever necessary, by column chromatography on
silicagel using appropriate solvent systems like
dichloromethane and petroleum ether etc. as eluents, to
afford pure thioether or thioester products. The physi-
cal properties and NMR spectra of compounds agreed
with those reported in the literature17–35 and were fur-
thermore identified by comparing the data with those of
authentic samples. The unknown compounds were
characterized by different spectroscopic techniques and
their elemental analyses.
In conclusion, CsF–Celite-assisted reactions provide an
easy access to thioethers as well as thioesters in good
yields. As this methodology has several advantages, it is
a valuable addition to existing methods. In short this is

S. T. A. Shah et al. / Tetrahedron Letters 43 (2002) 8281–8283
8283
an efficient, convenient, inexpensive, non-corrosive and
practical method for preparing thioethers and
thioesters.
15. (a) Iqbal, F.; Shekhani, M. S.; Malik, A.; Parvez, M.;
Riaz, U.; Ali, Z.; Khan, K. M. Z. Naturforsch. 2000, 55b,
317–320; (b) Saeed, M.; Abbas, M.; Khan, K. M.; Voel-
ter, W. Z. Naturforsch. 2001, 56b, 325–328; (c) Hayat, S.;
Atta-ur-Rahman; Choudhary, M. I.; Khan, K. M.;
Bayer, E. Tetrahedron Lett. 2001, 42, 1647; (d) Khan, K.
M.; Perveen, S.; Shah, S. T. A.; Shekhani, M. S.; Voelter,
W. New J. Chem. 2001, 896–898; (e) Zaidi, J. H.; Naeem,
F.; Iqbal, R.; Choudhary, M. I.; Khan, K. M.; Shah, S.
T. A.; Hayat, S.; Voelter, W. Z. Naturforsch. 2001, 56b,
689–696.
Acknowledgements
We express our gratitude to Deutscher Akademischer
Austauschdienst (DAAD, Bonn, Germany) for a sand-
wich-type scholarship, granted to Syed Tasadaque Ali
Shah and a short term scholarship, granted to Dr.
Khalid Mohammed Khan.
16. Hayat, S.; Atta-ur-Rahman; Choudhary, M. I.; Khan, K.
M.; Schumann, W.; Bayer, E. Tetrahedron 2001, 57,
9951–9957.
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