An efficient one-pot synthesis of bisalkylthioarenes

Article abstract of DOI:10.1016/j.tetlet.2003.11.015

Bisalkylthioarenes can be prepared efficiently from reactions between dihydroxyarenes and thiols under acidic conditions.

Full text of DOI:10.1016/j.tetlet.2003.11.015

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 457–459
An efficient one-pot synthesis of bisalkylthioarenesq
Porntip Charoonniyomporn,a Tienthong Thongpanchang,a,* Suteera Witayakran,a
Yodhathai Thebtaranonth,a Karen E. S. Phillipsb and Thomas J. Katzb
aDepartment of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand
bDepartment of Chemistry, Columbia University in the City of New York, New York, NY 10027, USA
Received 26 September 2003; revised 28 October 2003; accepted 7 November 2003
Abstract—Bisalkylthioarenes can be prepared efficiently from reactions between dihydroxyarenes and thiols under acidic condi-
tions.
Ó 2003 Published by Elsevier Ltd.
The procedure most commonly used in a number of
studies1 to synthesize aryl sulfides has been the coupling
of aryl halides and thiols.2 However, there are other
ways to prepare such structures. Particularly useful, if it
could be carried out easily and generally, would be to
replace the hydroxyl groups in phenols with alkylthio
groups.
Scheme 1. The Newman–Karnes alkylthioarene synthesis.
Newman and Karnes developed a procedure3 (shown in
Scheme 1) that works for a variety of phenols. The
process however takes four steps to achieve, and one of
them is a high-temperature rearrangement. Much easier
is the direct displacement of phenolic hydroxyls by thiols
under the influence of strong acid. Such transformations
were first demonstrated in 1960 by Furman et al., who
heated naphthols and thiols to 110–120 °C for a day
with very large amounts of p-toluenesulfonic acid and
little or no solvent.4;5 Subsequently, some examples were
described in which the acid was 12 M HCl, the temper-
ature was 180 °C, and the reaction times were 2–3 days.6
Another was described in which the reaction medium
was pure trifluoromethanesulfonic acid7 with reaction
temperature at 50 °C, and the reaction time was 3 h.
Here we report, with a number of examples employing
dihydroxyarenes, a practical procedure for carrying out
such transformations and some factors that affect the
yields.
1,4-Dihydroxynaphthalene was used for initial studies
following Russig8 and Laatsch,9 who reported that its
derivatives were regioselectively mono O-methylated by
methanol saturated with hydrogen chloride. However,
because it is easier to handle than gaseous hydrogen
chloride, p-toluenesulfonic acid was used.10 It was found
that when 1,4-dihydroxynaphthalene11 was refluxed in
benzene for 1 h with p-toluenesulfonic acid12 with a
variety of thiols, 1,4-bisalkylthionaphthalenes13 were
obtained in the yields summarized in Table 1 (entries 1–
6). These yields are higher when the thiols are primary
(entries 1 and 2) than when they are branched (entries 3
and 4).
The reactions of a variety of dihydroxyarenes and
n-propanethiol were then pursued to determine the
scope of the transformation (entries 7–14, Table 1). It
was found that 1,3-, 2,7-, and 1,6-dihydroxynaphtha-
lenes (entries 7, 9 and 10) and 9,10-dihydroxyanthracene
(entry 11) all gave good yields.14 2,3-Dihydroxynaph-
thalene gave a lower yield (entry 8), and catechol (entry
14) gave none of the expected product. In fact, of the
Keywords: Bisalkylthioarenes; Arylsulfides; Phenols; Thiols; Sulfides;
Displacement.
q Supplementary data associated with this article can be found at
doi:10.1016/j.tetlet.2003.11.015
* Corresponding author. Tel./fax: +66-2201-5139; e-mail: tettp@
mahidol.ac.th
0040-4039/$ - see front matter Ó 2003 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2003.11.015

458
P. Charoonniyomporn et al. / Tetrahedron Letters 45 (2004) 457–459
Table 1. Formation of bisalkylthioarenes by the reactions of diols with
thiolsa
p-TsOH
Ar(OH)2+RSH
Ar(OH)2
OH
Ar(SR)2
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒ!
benzene; reflux1h
Entry
1
R
Yield (%)
–CH2CH2CH3
96
Scheme 2.
OH
2
3
4
5
6
–CH2CH(CH3)2
–CH(CH3)2
–C(CH3)3
84
56
––
51
96
The different reactivities illustrated by the yields in Table
1 can be explained if the reactions require the carbonyl
groups of the carbon-protonated phenols to be conju-
gated with either a benzene ring or a b-alkoxy- (or
alkylthio-) substituted double bond. Accordingly, the
only benzenediols that reacted with thiols, like those
that react with alcohols, are those that have hydroxyl
groups meta to one another.17
–CH2Ph
–CH2CH2SH
OH
7
–CH2CH2CH3
98
OH
OH
OH
It should be possible to apply the procedure reported
here to prepare a variety of bisalkylthioarenes and a
variety of sulfur-containing heterocyclic compounds.
Research towards these goals is currently in progress.
8
9
46
94
HO
OH
OH
Acknowledgements
10
97
HO
Financial support from the Thailand Research Fund
(Grant PDF43) for T.T. and from the Postgraduate
Education and Research Program in Chemistry for P.J.
and S.W. is gratefully acknowledged. Y.T. thanks
BIOTEC for financial support through a Senior
Research Fellowship.
OH
11
12
77
59
OH
OH
HO
References and Notes
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13
14
4
HO
OH
OH
OH
––
a Yields are those of purified materials, but they are not optimized. The
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thiols they give bisthioethers. This could reflect the
greater nucleophilicities of thiols compared to alcohols.16

P. Charoonniyomporn et al. / Tetrahedron Letters 45 (2004) 457–459
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