Thiolysis of 1,2-epoxides by thiophenol catalyzed under solvent-free conditions

Article abstract of DOI:10.1016/S0040-4039(03)01704-0

Thiolysis of alkyl- and aryl-1,2-epoxides was investigated under solvent-free conditions in the presence of Lewis and Br?nsted acid and base catalysts (InCl₃, p-TsOH, n-Bu₃P, K₂CO₃). Five mol% of catalyst was su

Full text of DOI:10.1016/S0040-4039(03)01704-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6785–6787
Thiolysis of 1,2-epoxides by thiophenol catalyzed under
solvent-free conditions
Francesco Fringuelli, Ferdinando Pizzo,* Simone Tortoioli and Luigi Vaccaro
Dipartimento di Chimica, Universita` di Perugia, Via Elce di Sotto, 8 I-06123, Perugia, Italy
Received 9 June 2003; revised 12 June 2003; accepted 12 June 2003
Abstract—Thiolysis of alkyl- and aryl-1,2-epoxides was investigated under solvent-free conditions in the presence of Lewis and
Brønsted acid and base catalysts (InCl3, p-TsOH, n-Bu3P, K2CO3). Five mol% of catalyst was sufficient and the best results were
obtained by using InCl3 and K2CO3. b-Hydroxy sulfide was isolated in excellent yields.
© 2003 Elsevier Ltd. All rights reserved.
To minimize the amount of harmful organic solvents
used in chemical processes, much attention has been
devoted to the use of alternative reaction media.1
Besides the use of supercritical fluids, water, and ionic
liquids, the possibility of performing chemical processes
in the absence of solvent (solvent-free conditions) has
been receiving more attention.1b,2 For historical and
cultural reasons, organic reactions have generally been
developed in solution while, a higher chemical efficiency
would be expected if there were no medium interposed
between the reactants. The examples reported demon-
strate that no-solvent reactions are generally faster, give
higher selectivities and yields, and usually require easier
work-up procedures and simpler equipment.2,3
The thiolysis of 1,2-epoxides is a convenient synthetic
tool for preparing b-hydroxy sulfides, which are an
important class of intermediates in organic synthesis.8
To the best of our knowledge there has only been one
report of the thiolysis of 1,2-epoxides performed under
solvent-free conditions; Penso et al. used tetra-
butylammonium fluoride (5 mol%) as a basic catalyst.9
In this letter we report the catalytic efficiency of Lewis
and Brønsted acid and base catalysts in a solventless
thiolysis of alkyl- and aryl-1,2-epoxides. The reactions
were carried out at 30°C in the presence of 5 mol%
catalyst using 1.05 mol equiv. of thiophenol.
InCl3 was chosen as a representative Lewis acid, p-tolu-
ensulfonic acid (p-TsOH) as a Brønsted acid, n-Bu3P as
a Lewis base, and K2CO3 as a Brønsted base. Alkyl-
and arylsubstituted-1,2-epoxides 1–7 were selected as
substrates and the results are reported in Table 1. After
2 weeks (336 h) the reactions performed in the absence
of catalyst only gave a small % of conversion (see Table
1, footnote a).
For many years, we have been interested in using
alternative reaction media to contribute to the develop-
ment of an environmentally-responsible chemistry and
our research has been focused on the use of water as
reaction medium.4 We have found that Lewis acids
catalyze the regio- and stereoselective iodolysis and
azidolysis of a,b-epoxycarboxylic acids in water5 and
we have also shown that InCl3 is an efficient catalyst
for the thiolysis of oxiranes in water at pH 4.0.6 In the
area of solvent-free reactions, we have recently
reported7 the trimethylsilylation of alcohols catalyzed
by tetramethylammonium bromide,7a and the [4+2]
cycloaddition reaction between 3-nitrocoumarins and
vinyl ethers.7b
InCl3 was chosen because it is a very efficient catalyst
for this transformation in water6 and in dichloro-
methane, as recently reported by Yadav et al.10 This
salt was generally more efficient under solvent-free con-
ditions than under solvent conditions; lower catalyst
loadings (5 mol% versus 10 mol%) could be used.
Complete conversions were obtained in all the reactions
in 1 min with the exception of the thiolyses of 4, 6 and
7. With a 5 mol% loading the reaction of 6 stopped at
51% conversion (entry 23) but with 10 mol% of InCl3
the conversion reaction reached 80% (entry 24). In the
case of 1,2-epoxide 7 the reaction was complete in 10
Keywords: 1,2-epoxides; Lewis catalysts; Brønsted catalysts; solvent-
free conditions.
* Corresponding author. Tel.: +39 075 5855546; fax: +39 075
5855560; e-mail: pizzo@unipg.it
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01704-0

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F. Fringuelli et al. / Tetrahedron Letters 44 (2003) 6785–6787
efficiency was shown in the thiolysis of 1; after 48 h the
corresponding b-hydroxy phenylsulfide was obtained in
quantitative yield (entry 2). When the same reaction
was performed in dichloromethane, less than 2% con-
version was obtained after 48 h. In the case of 1,2-epox-
ide 7, the reaction was complete in 48 h (entry 30) but
due to the very high reactivity of benzylic system, the
additional side-product 8 (17% of the mixture) was also
found (see Table 1, footnote g). Under these reaction
conditions we suppose that the thiiranium ion was
formed and reacted with phenylthiol to give 8.
min (entry 28) but the side-product 1,2-bis(phenylthio)-
ethylbenzene (8) (50% of the mixture) was also found
(see Table 1, footnote e). By reducing the amount
of InCl3 from 5 to 1 mol%, the side-product 8 was
reduced to 8% of the reaction mixture (entry 29, foot-
note f).
p-TsOH showed a poor catalytic effect in the reaction
of 1,2-epoxides 2, 3, 5, and 7 (Table 1, entries 6, 11, 19,
and 30) while the effect was completely unsatisfactory
for substrates 4 and 6 (entries 15 and 25). The highest
Table 1. Acid- or base-catalyzed thiolysis of 1,2-epoxides under solvent-free conditions

F. Fringuelli et al. / Tetrahedron Letters 44 (2003) 6785–6787
6787
n-Bu3P was chosen to compare the results with those
recently published by Hou et al. who found that this
catalyst (used in 10 mol% amount) efficiently catalyzed
the ring-opening of 1,2-epoxides and aziridines in water
but was not effective when the reactions were carried
out in acetonitrile.11 To confirm these results we
repeated the reaction of 1 in dichloromethane and we
found that after 200 h ca. 3% conversion was obtained.
Our results showed that in the absence of solvent,
n-Bu3P (5 mol%) has a good catalytic efficiency with all
the substrates except 3 where 10 mol% of catalyst was
used and 5 in which the reaction conversion was only
33% after ca. 500 h (entry 22).
and then 1,2-epoxide (1.0 mmol) was added. After the
times reported, the reaction mixtures with InCl3,
K2CO3 and p-TsOH were treated in diethyl ether, the
organic phase was washed with water to remove the
catalyst and was worked-up as usual. n-Bu3P was
removed directly by re-crystallization in the cases of
solid products, or by filtration through silica gel in the
cases of oily products.
Acknowledgements
The Ministero dell’Istruzione dell’Universita` e della
Ricerca (MIUR) and the Universita` degli studi di Peru-
gia are thanked for financial support.
Finally, K2CO3 was the best base catalyst, showing a
very high catalytic efficiency with complete conversion
after 1–24 h except in the less reactive substrates 2 and
5 where expected longer reaction times were observed
(entries 7 and 20). By increasing the catalyst amount to
10 mol%, the conversions of 2 and 5 were accomplished
after 300 h (entries 8 and 21).
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As expected, the regioselectivity of the process is
strongly dependant on the acidity or basicity of the
reaction conditions and the data obtained under sol-
vent-free conditions are comparable to those obtained
in aqueous or organic solvent conditions.6,10 Acidic
conditions (InCl3 or p-TsOH as catalysts) favored the
nucleophilic attack of thiol at the more-substituted
a-carbon, depending on the substituents on the oxirane-
ring. An almost complete a-regioselectivity was
obtained with 7 (entry 29) while a/b ratios of 55/45 or
69/31 were observed with 2 and 5, respectively (entries
5 and 18). As expected, under basic conditions (n-Bu3P
or K2CO3 as catalysts), the less-substituted b-carbon
was more favored and a good to high b-regioselectivity
was found. In particular in the case of styrene oxide (7)
a 40/60 a/b ratio was obtained (entry 31), while in
aqueous or organic media, an a-attack was largely
predominant.6,10
In conclusion we have reported the thiolysis of alkyl-
and aryl-1,2-epoxides under solvent-free conditions cat-
alyzed by p-TsOH, InCl3, K2CO3 and n-Bu3P (5 mol%)
as representative catalysts. The best results were
obtained using InCl3 and K2CO3. Under solventless
conditions smaller catalyst loadings and reaction times
were observed with respect to those obtained in
aqueous6,11 or organic media.10,11
In our opinion, these results are extremely promising
and work is in progress to improve catalyst efficiency
and to apply the solvent-free thiolysis of 1,2-epoxides to
the synthesis of target molecules.
10. Yadav, J. S.; Reddy, B. V. S.; Baishya, G. Chem. Lett.
2002, 906–907.
11. Fan, R.-H.; Hou, X.-L. J. Org. Chem. 2003, 68, 726–730.
Typical experimental procedure: In an oven-dried screw-
capped vial thiophenol (1.05 mmol, 0.108 mL) was
stirred with the catalyst (5 mol%) for 10 min at 30°C