Thiolysis in sole water was first investigated in our
laboratory.8g,10 Under basic conditions (pH 9.0), the
nucleophilic attack occurs, as expected, almost exclusively
on the less substituted carbon of the oxirane-ring.8g
We found10 that under acidic conditions (pH 4.0), it was
possible to partially modify the regioselectivity of the
reaction allowing the thiophenol attack on the more
substituted R-carbon. The reactions, however, were ex-
tremely slow and led to the formation of undesired side
products. At pH 4.0, InCl3 (10 mol %) was a very efficient
catalyst, which gave the same regioselectivity results but
in very short reaction times. Our previous studies8g,10
would seem to indicate that under neutral conditions (pH
7.0) this reaction should be slow and that a metal catalyst
would therefore be necessary. While many Lewis acids
have proven to be very efficient in sole water under acidic
conditions, the same catalysts are generally not effective
under neutral or basic conditions.11
Zn (II)-Ca ta lyzed Th iolysis of Oxir a n es in
Wa ter u n d er Neu tr a l Con d ition s
Francesco Fringuelli, Ferdinando Pizzo,*
Simone Tortoioli, and Luigi Vaccaro
Universita` di Perugia, Dipartimento di Chimica,
Via Elce di Sotto, 8 I-06100 Perugia, Italy
pizzo@unipg.it
Received J une 13, 2003
Abstr a ct: Thiolysis of a variety of 1,2-epoxides in water at
30 °C and pH 7.0 is strongly accelerated by ZnCl2 (10 mol
%) except when amino- and carboxythiophenol are used. The
aqueous medium and the catalyst were recovered and reused
in various runs without affecting the efficiency of the process.
In tr od u ction
Metal-thiol and metal-thiolate interactions are ex-
tremely important in biochemical processes;12 in fact, in
vivo Nature regulates the catalytic efficiency of biocata-
lysts such as Co(II), Ni(II), Cu(II), and Zn(II) exploiting
their interactions with sulfur-containing functionalities.13
This biological behavior would suggest that these cations
could be efficient catalysts in water even under neutral
conditions. Their pK1,1 hydrolysis constants (9.65, 9.86,
7.97, and 8.96, respectively)14 confirm this hypothesis
because at pH 7.0 (below their pK1,1) their highest
efficiency is expected.11e,f
The â-hydroxysulfide unit is present in compounds of
biological and pharmacological interest1 and is a versatile
moiety for synthesizing allylic alcohols,2 benzoxathi-
epines,3 benzotiazepines,4 R-thioketones,5 R-substituted
R,â-unsaturated enones,6 and â-hydroxysulfoxides used
in the synthesis of naturally occurring compounds.7
The easiest access to â-hydroxysulfides is the thiolysis
of 1,2-epoxides that is usually carried out in organic
solvents (THF, CH2Cl2, MeOH, MeCN, or PhH) by using
thiols under basic conditions8 or in the presence of
promotors and/or catalysts.9
From a chemical perspective, Co(II), Ni(II), Cu(II), and
Zn(II) salts are classic Lewis acids that could offer the
* Corresponding author.
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10.1021/jo0348266 CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/12/2003
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J . Org. Chem. 2003, 68, 8248-8251