Selenonium ionic liquid as an efficient catalyst for the synthesis of thioacetals under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2008.01.096

Acidic ionic liquid butyl ethyl phenyl selenonium tetrafluoroborate, [BEPSe]BF₄, was successfully employed as a catalyst for the synthesis of several dithioacetals in the absence of a solvent. The method is general and selectively afforded thioacetals derived from aldehydes and ketones in good yields.

Full text of DOI:10.1016/j.tetlet.2008.01.096

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Tetrahedron Letters 49 (2008) 1919–1921
Selenonium ionic liquid as an efficient catalyst for the synthesis
of thioacetals under solvent-free conditions
Eder J. Lenardao *, Elton L. Borges, Samuel R. Mendes, Gelson Perin, Raquel G. Jacob
˜
ˆ
Instituto de Quı´mica e Geociencias, LASOL, Universidade Federal de Pelotas, UFPel, PO Box 354, 96010-900 Pelotas, RS, Brazil
Received 4 December 2007; revised 15 January 2008; accepted 24 January 2008
Available online 30 January 2008
Abstract
Acidic ionic liquid butyl ethyl phenyl selenonium tetrafluoroborate, [BEPSe]BF4, was successfully employed as a catalyst for the
synthesis of several dithioacetals in the absence of a solvent. The method is general and selectively afforded thioacetals derived from
aldehydes and ketones in good yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Thioacetals; Selenonium salts; Solvent-free conditions
The protection of carbonyl compounds as thioacetals
has attracted great interest in organic synthesis,1 especially
due to their versatility, since they can also be used as nucle-
ophilic acylating agents,1c,d masked methylene functions,1e
and in the asymmetric synthesis of homoallylic thioethers.1f
A number of methods for the dithioacetalization of
carbonyl compounds have been described, including the
use protic or Lewis acids in the presence of organic sol-
vents1a and solid-supported Lewis acids under solvent-free
conditions.1b,2 On the other hand, room-temperature ionic
liquids are receiving much attention in organic chemistry as
reaction solvents and catalysts.3 Product isolation or cata-
lyst recycling is very easy in ionic liquids and in some cases,
rate accelerations and/or selectivity improvements are also
observed. Recently, the preparation of dithioacetals start-
ing from aldehydes was described using BMIMBF4 at
room temperature as solvent,4a while molten TBAB
(110 °C) was used as a catalyst in the transthioacetalization
of acetals.4b
development of new cleaner protocols for classical reac-
tions.6,7 In continuation to our studies on the development
of new protocols under solvent-free conditions, we wish to
report here the use of a new Se-based ionic liquid, phenyl
butyl methyl selenonium tetrafluoroborate ([BEPSe]BF4,
3),7 as catalyst in the preparation of dithioacetals from
aldehydes and ketones (Scheme 1, Table 1).8
Accordingly, when benzaldehyde (1a; 1.0 mmol) was
treated with phenylthiol (2a; 2.2 mmol) in presence of
[BEPSe]BF4 (15 mol %) at room temperature, benzalde-
hyde dithiophenylacetal (4a) was obtained in 83% yield
after 2.5 h (Table 1, entry 1).
When the same reaction was performed in the presence
of a smaller amount of [BEPSe]BF4 (5 mol %), an incom-
plete consumption of starting materials, even after stirring
for 24 h was observed. The use of a larger amount of 3
(25 mol %) has not significantly increased the yield of 4a.
+
Our major research goal has been the development
of new methods for the preparation and synthetic
applications of organochalcogenium compounds5 and the
-
C4H9 Se
C2H5
BF4
C6H5
O
R2S
R
SR2
R1
R2SH
(15 mol %)
r.t., without solvent
3
+
R1
R
1
2
4
*
Corresponding author. Tel./fax: +55 53 3275 7354.
Scheme 1.
E-mail address: lenardao@ufpel.edu.br (E. J. Lenardao).
˜
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.096

1920
E. J. Lenarda˜o et al. / Tetrahedron Letters 49 (2008) 1919–1921
Table 1
Conversion of aldehydes and ketones to thioacetals 4
Entry
R
R1
Thiol (2)
Product (4)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
a
C6H5
C6H5
C6H5
C3H7
C4H9
C4H9
H
H
H
H
H
H
H
CH3
CH3
C6H5SH 2a
4a
4b
4c
4d
4e
4f
2.5
2.0
2.5
3.5
3.5
2.5
1.5
4.5
5.0
5.5
4.0
2.5
5.0
24
83
97
75
58
66
78
83
46
44
25
65
80
58
7
p-ClC6H4CH2SH 2b
C6H5CH2SH 2c
C6H5SH 2a
C6H5SH 2a
C6H5CH2SH 2c
C6H5SH 2a
(E/Z)-Me2C@CHCH2CH2C(Me)@CH
CH3
CH3
4g
4h
4i
C6H5CH2SH 2c
p-ClC6H4CH2SH 2b
p-ClC6H4CH2SH 2b
C6H5CH2SH 2c
CH3(CH2)11SH 2d
C6H5CH2SH 2c
C6H5SH 2a
2-Tetralone
2-Tetralone
2-Tetralone
4j
4k
4l
–CH2CH2CH2CH2CH2CH2–
C6H5
C6H5
4m
4n
4o
4p
C6H5
H
HSCH2CH2SH 2eb
HSCH2CH2SH 2eb
3
5
96
88
–CH2CH2CH2CH2CH2CH2–
Yields of pure products isolated by column chromatography (hexanes) and identified by mass spectrometry, 1H and 13C NMR.1,2
1.0 equiv of 1,2-ethanedithiol was used.
b
The experimental procedure is very easy, and a complete
Acknowledgments
conversion of starting materials to products was observed
after stirring for a few hours at room temperature. The effi-
ciency of the method can be clearly visualized by the reac-
tion of benzaldehyde (1a) with 4-chlorobenzylthiol (2b)
affording the respective dithioacetal 4b in almost quantita-
tive yield (Table 1, entry 2). The scope of our methodology
was successfully expanded to other aromatic and aliphatic
aldehydes and thiols (Table 1, entries 3–7). The present
thioacetalization procedure is also applicable to aliphatic
ketones (Table 1, entries 8–14), affording the respective
dithioacetals in reasonable yields, except for the condensa-
tion of benzophenone with phenylthiol (2a, entry 14). On
the other hand, the Se-ionic liquid 3 can also be used in
the selective protection of the a,b-unsaturated aldehyde
citral as the respective dithioacetal 4g, without the forma-
tion of the Michael-adduct (Table 1, entry 7). Besides,
when 1,2-ethanedithiol (2e, 1 equiv) was employed, the
preparation of 1,3-dithiolanes was possible in good yields
(Table 1, entries 15 and 16).
As the preparation of thioacetals from aldehydes is
kinetically favorable, as shown in Table 1, we investigated
the ability to chemoselectively protect an aldehyde in the
presence of a ketone under our best conditions. Thus, when
an equimolar mixture of benzaldehyde and cyclohexanone
was allowed to react with benzenemethanethiol (2c) in the
presence of a catalytic amount of [BEPSe]BF4, the thio-
acetal derived from benzaldehyde (4c) was obtained almost
exclusively (73% yield) with a little amount of the protected
ketone 4m (3% yield) after 5 h.
This project is funded by CNPq and FAPERGS. Profes-
sor C. C. Silveira (UFSM/Brazil) is acknowledged for the
1H and 13C NMR analysis.
References and notes
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1991; (b) Sartori, G.; Ballini, R.;
Bigi, F.; Bosica, G.; Maggi, R.; Righi, P. Chem. Rev. 2004, 104, 199; (c)
Corey, E. J.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1965, 4, 1075;
(d) Corey, E. J.; Seebach, D. J. Org. Chem. 1966, 31, 4097; (e) Bulman
Page, P. C.; van Niel, M. B.; Prodger, J. C. Tetrahedron 1989, 45, 7643;
(f) Liu, P.; Binnun, E. D.; Schaus, J. V.; Valentino, N. M.; Panek, J. S.
J. Org. Chem. 2002, 67, 1705.
2. See, for instance: (a) Firouzabadi, H.; Iranpoor, N.; Karimi, B.
Synthesis 1999, 58; (b) Firouzabadi, H.; Karimi, B.; Eslami, S.
Tetrahedron Lett. 1999, 40, 4055; (c) Zahouily, M.; Mezdar, A.;
Elmakssoudi, A.; Mounir, B.; Rayadh, A.; Sebti, S.; Lazrek, H. B.
Arkivoc 2006, 31.
3. For reviews on preparation, characterization and use of ionic liquids
see, for instance: (a) Paˆrvulescu, V. I.; Hardacre, C. Chem Rev. 2007,
107, 2615; (b) Dupont, J.; Souza, R. F.; Suarez, P. A. Z. Chem. Rev.
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Chem. Soc. 2000, 11, 337; (d) Consorti, C. S.; Souza, R. F.; Dupont, J.;
Suarez, P. A. Z. Quı´m. Nova 2001, 24, 830; (e) Wasserscheid, P.;
Welton, T. Ionic Liquids in Synthesis; Wiley-VCH: New York, 2002; (f)
Welton, T. Chem. Rev. 1999, 99, 2071; (g) Wassercheid, P.; Keim, W.
Angew. Chem., Int. Ed. 2000, 39, 3772; (h) Davis, J. H., Jr.; Fox, P. A.
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672; (b) Ranu, B. C.; Das, A.; Samanta, S. J. Chem. Soc., Perkin Trans.
1 2002, 1520.
In conclusion, we presented here an easy and general
method for the selective conversion of aromatic, aliphatic,
a,b-unsaturated aldehydes and ketones to their corres-
ponding dithioacetals. This method consists in low con-
sumption of solvent, mild reaction conditions, good
yields, and use of catalytic amount of ionic liquid with
non-aqueous work-up.
5. (a) Lenardao, E. J.; Ferreira, P. C.; Jacob, R. G.; Perin, G.; Leite, F. P.
˜
L. Tetrahedron Lett. 2007, 48, 6763; (b) Lenardao, E. J.; Lara, R. G.;
˜
Silva, M. S.; Jacob, R. G.; Perin, G. Tetrahedron Lett. 2007, 48, 7668;
(c) Perin, G.; Jacob, R. G.; Azambuja, F.; Botteselle, G. V.; Siqueira,
G. M.; Freitag, R. A.; Lenardao, E. J. Tetrahedron Lett. 2005, 46,
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1679; (d) Perin, G.; Jacob, R. G.; Botteselle, G. V.; Kublik, E. L.;
Lenardao, E. J.; Cella, R.; Santos, P. C. S. J. Braz. Chem. Soc. 2005,
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16, 857.

E. J. Lenarda˜o et al. / Tetrahedron Letters 49 (2008) 1919–1921
1921
6. (a) Jacob, R. G.; Perin, G.; Loi, L. N.; Pinno, C. S.; Lenardao, E. J.
˜
2.2 mmol), ½BEPSeꢀBF74 (3, 0.049 g, 15 mol %) was added and the
solution stirred at room temperature for 2.5 h. The crude product was
purified by column chromatography over silica gel (SiO2) eluting with
hexanes, yielding product 4a (0.256 g, 83%) as a light yellow oil. 1H
NMR (200 MHz, CDCl3) d (ppm) 7.32–7.40 (m, 6H); 7.20–7.27 (m,
9H); 5.42 (s, 1H); 13C NMR (50 MHz, CDCl3) d (ppm) 133.8, 130.0,
129.5, 128.3, 78.5, 78.4, 78.0, 61.3.1f
Tetrahedron Lett. 2003, 44, 3605; (b) Jacob, R. G.; Perin, G.;
Botteselle, G. V.; Lenardao, E. J. Tetrahedron Lett. 2003, 44, 6809.
˜
7. Lenardao, E. J.; Mendes, S. R.; Ferreira, P. C.; Perin, G.; Silveira, C.
˜
C.; Jacob, R. G. Tetrahedron Lett. 2006, 47, 7439.
8. General procedure for the synthesis of thioacetals: To a mixture of
benzaldehyde (1a, 0.106 g; 1 mmol) and phenylthiol (2a, 0.242 g;