Unusual cleavage of ethers by thiophenol on the surface of silica gel impregnated with indium(III) chloride under microwave irradiation: Efficient procedure for the synthesis of thioethers through transthioetherification

Article abstract of DOI:10.1055/s-2002-31911

Cyclic and open-chain benzylic ethers undergo cleavage by thiophenol on the surface of silica gel impregnated with indium(III) chloride under microwave irradiation to produce the corresponding di- and monothioethers.

Full text of DOI:10.1055/s-2002-31911

LETTER
987
Unusual Cleavage of Ethers by Thiophenol on the Surface of Silica Gel Im-
pregnated with Indium(III) Chloride under Microwave Irradiation: Efficient
Procedure for the Synthesis of Thioethers through Transthioetherification
U
nusual Cleavage
r
of
E
the
i
rs by
T
n
hiophenol daban C. Ranu,* Sampak Samanta, Alakananda Hajra
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta-700 032, India
Fax +91(33)4732805; E-mail: ocbcr@mahendra.iacs.res.in
Received 7 March 2002
microwave irradiation and presence of catalytic amount
(20–30 mol%) of indium(III) chloride on silica gel surface
is also essential for the reaction to proceed.
Abstract: Cyclic and open-chain benzylic ethers undergo cleavage
by thiophenol on the surface of silica gel impregnated with indi-
um(III) chloride under microwave irradiation to produce the corre-
sponding di- and monothioethers.
Several structurally diverse cyclic and open-chain ethers
Key words: cleavage of ether, thiophenol, indium(III) chloride, underwent cleavages by thiophenol and its derivatives by
thioether, microwave, transthioetherification
this procedure to provide the corresponding di- and mono-
thioethers. The results are presented in Table. It was evi-
dent from the results in Table that although this procedure
works very efficiently for the conversion of open-chain
benzylic ethers to the corresponding thioethers, nonben-
zylic dialkyl ether (entry 18) and phenyl (aryl) alkyl ether
remained inert (entry 10). Presumably, this Lewis acid
(InCl3) catalyzed nucleophilic cleavage of ether by
thiophenol requires a considerable electronic influence on
the carbon atom of the C-O bond to be cleaved and hence
is facilitated in benzylic ethers having such effect (entry
17). Thus, selective cleavage of benzyl alkyl ether in pres-
ence of phenyl methyl one is achieved efficiently (entries
11–14). On the other hand, in the reaction of benzyl p-sub-
stituted benzyl ethers, preferential cleavage at the C-O
bond adjacent to substituted phenyl ring occurs providing
the corresponding thioethers as major products (entries
11, 13–15). It was also found that cleavages of open-chain
ethers are relatively clean furnishing higher yields of
products compared to those of cyclic ethers.
Recently, we have developed an efficient procedure for
the synthesis of quinolines by a one-pot reaction of
anilines with methyl vinyl ketone on the surface of silica
gel impregnated with indium(III) chloride under micro-
wave irradiation.1 Obviously, this process involves
Michael addition of aniline to methyl vinyl ketone fol-
lowed by subsequent cyclization and aromatization under
the reaction conditions. Thus, as a logical manipulation
we then tried same procedure with thiophenol replacing
aniline for access to the corresponding sulfur-heterocycle.
However, to our surprise no expected cyclized product
was obtained and we isolated a dithioether which corre-
sponds to be formed by the cleavage of tetrahydrofuran,
possibly left over in trace amount during impregnating sil-
ica gel with a THF solution of indium(III) chloride, by
thiophenol (Scheme). This hypothesis was established by
the formation of the same compound on treatment of
thiophenol with THF on silica gel surface in presence of
InCl3 under microwave irradiation.
In conclusion, the present procedure provides a very sim-
ple and efficient cleavage of cyclic ethers like tetrahydro-
furan and tetrahydropyran and open-chain benzylic
ethers3 by thiophenol producing the corresponding di- and
monothioethers respectively in good yields. Nevertheless,
this protocol constitutes a novel and new approach for the
protection of thiophenol as thioethers4 through transthio-
etherification of alkyl ethers. Further investigations to
broaden the scope of this reaction are also being pursued.
Scheme
This prompted us to initiate a systematic investigation of
this unusual cleavage of THF by thiophenol. We have dis-
covered that this is a general reaction for the cleavage of
cyclic and open-chain benzylic ethers by thiophenol and
its derivatives producing the corresponding di- and mono-
thioethers respectively.2 It was also observed that no reac-
tion occurred under conventional heating without
Acknowledgement
We are pleased to acknowledge the financial support from CSIR,
New Delhi [Grant No. 01(1739)/02] for this investigation. S. S. and
A. H. are also thankful to CSIR for their fellowships.
Synlett 2002, No. 6, 04 06 2002. Article Identifier:
1437-2096,E;2002,0,06,0987,0989,ftx,en;G06902ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

988
B. C. Ranu et al.
LETTER
Table Transthioetherification of Ethers by Thiophenol
Entry
1
Ether
Thiol
PhSH
Time (min)
10
Product
Yield (%)a
PhS(CH2)4SPh
82
69
2
3
4
4-Cl-C6H4SH
PhSH
10
10
10
PhS(CH2)5SPh
61
53
4-Cl-C6H4SH
5
6
7
8
PhCH2OCH2Ph
PhCH2OCH2Ph
PhCH2OMe
PhSH
10
15
15
11
PhCH2SPh
85
71
69
89
4-Cl-C6H4SH
PhSH
4-Cl-C6H4SCH2Ph
PhCH2SPh
PhSH
9
4-Cl-C6H4SH
12
78
89
10
11
PhOMe
PhSH
PhSH
15
11
No reaction
(84:16)b
(75:25)b
12
13
PhSH
PhSH
12
12
83
86
(75:25)b
(75:25)b
14
15
PhSH
PhSH
12
14
81
68
(65:35)b
16
PhSH
12
87
73
17
18
PhCH2CH2OCH2Ph
CH3(CH2)8CH2OMe
PhSH
PhSH
15
15
PhCH2SPh
No reaction
a Yields refer to those of pure isolated products characterized by spectral data (1H NMR, 13C NMR).
b The ratio was determined by 1H NMR.
Synlett 2002, No. 6, 987–989 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Unusual Cleavage of Ethers by Thiophenol
989
mixture was then eluted with ether and the ether extract was
washed with 10% NaOH solution followed by brine and
dried. Evaporation of solvent and purification of the crude
product by column chromatography over silica gel (hexane–
ether, 9:1) furnished the pure product (225 mg, 82%) as a
colorless solid, mp 79-80 °C, IR: 2947, 1581, 1479, 1436,
731 cm–1; 1H NMR 7.34-7.15 (m, 10 H), 2.96-2.89 (m, 4
H), 1.82-1.76 (m, 4 H); 13C NMR 136.8 (2C), 129.6 (4C),
129.3 (4C), 126.3 (2C), 33.6 (2C), 28.5 (2C); MS: m/e = M+
274(29), 165(95), 135(10), 123(100), 109(44). Anal. Calcd
for C16H18S2: C, 70.07; H, 6.57. Found: C, 70.01; H, 6.53.
(3) Reviews on cleavage of ethers : (a) Ranu, B. C.; Bhar, S.
Org. Prep. Proced. Int. 1996, 28, 371. (b) Tiecco, M.
Synthesis 1988, 749. (c) Maercker, A. Angew. Chem. Int.
Ed. Engl. 1987, 26, 972.
References
(1) Ranu, B. C.; Hajra, A.; Jana, U. Tetrahedron Lett. 2000, 41,
531.
(2) General Experimental Procedure. Representative one
for the cleavage of THF by thiophenol. A mixture of THF
(108 mg, 1.5 mmol) and thiophenol (110 mg, 1 mmol) was
added to the surface of silica gel (1 g) impregnated with
indium(III) chloride (66 mg, 0.3 mmol, 30 mol%) [The
impregnation procedure is as follows: A solution of InCl3 in
a minimum amount of EtOH was added to silica gel HF254
(E. Merck), activated by heating at 150 °C for 3 h under
reduced pressure and the mixture was stirred for 5 minutes at
room temperature. Evaporation of solvent under vacuum
furnished the catalyst ready for use] under stirring for
uniform mixing. The whole mixture in a pyrex round
bottomed flask was then irradiated with microwave in a
domestic microwave oven (manufactured by BPL-Sanyo,
India; 2450 MHz) at 240 W (20% power) for a certain period
of time (with a brief interval after every 5 minutes of
heating) as required to complete the reaction. The reaction
(4) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd Ed.; Wiley: New York, 1999, 454.
(b) Schopfer, U.; Schlapbach, A. Tetrahedron 2001, 57,
3069; and references cited therein.
Synlett 2002, No. 6, 987–989 ISSN 0936-5214 © Thieme Stuttgart · New York