Application of BU4N+HSO4- as an ionic liquid and acid catalyst for thioacetalization of aldehydes and ketones

Article abstract of DOI:10.1080/10426500801967757

A variety of carbonyl containing compounds have been successfully reacted with 1,2-ethanedithiol in a thioacetylization reaction using tetrabutylammonium hydrogensulfate as a mild and efficient catalyst. Aldehydes and ketones react with good to excellent

Full text of DOI:10.1080/10426500801967757

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Application of BU4N+HSO4
as an Ionic Liquid and Acid
Catalyst for Thioacetalization
of Aldehydes and Ketones
Abdol R. Hajipour a b , Peyman Hosseini a & Arnold
E. Ruoho b
a Pharmaceutical Research Laboratory, College
of Chemistry , Isfahan University of Technology ,
Isfahan, Iran
b Molecular and Cellular Pharmacology , University
of Wisconsin Medical School , Madison, Wisconsin,
USA
Published online: 27 Sep 2008.
To cite this article: Abdol R. Hajipour , Peyman Hosseini & Arnold E. Ruoho (2008)
Application of BU4N+HSO4 - as an Ionic Liquid and Acid Catalyst for Thioacetalization
of Aldehydes and Ketones, Phosphorus, Sulfur, and Silicon and the Related Elements,
183:10, 2502-2508, DOI: 10.1080/10426500801967757
To link to this article: http://dx.doi.org/10.1080/10426500801967757
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Phosphorus, Sulfur, and Silicon, 183:2502–2508, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801967757
Application of BU4N+HSO− as an Ionic Liquid and Acid
Catalyst for Thioacetalizat4ion of Aldehydes and Ketones
Abdol R. Hajipour,1,2 Peyman Hosseini,1 and
Arnold E. Ruoho2
1Pharmaceutical Research Laboratory, College of Chemistry, Isfahan
University of Technology, Isfahan, Iran
2Molecular and Cellular Pharmacology, University of Wisconsin Medical
School, Madison, Wisconsin, USA
A variety of carbonyl containing compounds have been successfully reacted with
1,2-ethanedithiol in a thioacetylization reaction using tetrabutylammonium hydro-
gensulfate as a mild and efficient catalyst. Aldehydes and ketones react with good
to excellent yields under mild conditions.
Keywords Acid catalyst; carbonyl compound; ionic liquid; thioacetalization
INTRODUCTION
The protection of aldehydes and ketones as thioacetal and thioke-
tals is a widely used method, which is performed in the presence of
acids, generally.1 They are quite stable under basic or mildly acidic
conditions.2 The dithioacetals are also utilized as masked acyl anions3
or masked methylene function groups4 for carbon–carbon bond for-
mation. Generally, these compounds are prepared by condensation of
carbonyl compounds with thiols or dithiols employing acid catalysts in-
cluding HCl,5 PTSA,6 BF3.OEt2,7 AlCl3,8 TiCl4,9 Mg(OTf)3,10 LaCl3,11
SiCl4,12 WCl6,13 (CH3)3SiCl,14 5 M LiClO4,15 SOCl2–SiO2,16 Cu(OTf)2–
SiO127, ZrCl4–SiO2,18 TaCl5–SiO2,19CoBr2–SiO2,20 LiBr,21a LiBF4,22a
InCl3,23 molecular I2,24a NBS,25 and Sc(OTf)3.26
Received 6 November 2007; accepted 12 January 2008.
We gratefully acknowledge the funding support received for this project from the
Isfahan University of Technology (IUT), I.R. Iran (A. R. H.), and Grants GM 033138,
MH 065503, NS 033650 (A. E. R.) from the National Institutes of Health, USA. Further
financial support from Center of Excellency in Chemistry Research (IUT) is gratefully
acknowledged.
Address correspondence to A. R. Hajipour, Pharmaceutical Research Labora-
tory, College of Chemistry, Isfahan University of Technology, Isfahan, Iran. E-mail:
Haji@cc.iut.ac.ir
2502

A. R. Hajipour et al.
2503
Some of these methods suffer from some drawbacks such as te-
dious work-up,9,10 using relatively expensive reagents,10–15 harsh
conditions16 or require an inert atmosphere for the reaction.15,23–25
Therefore, an introduction of new methods and inexpensive reagents
for such functional group transformations is still in demand.
Ionic liquids have attracted extensive research interest in recent
years as environmentally benign solvents due to their favorable prop-
erties like non-flammability, negligible vapor pressure, reusability, and
high thermal stability. They have also been referred to as designer sol-
vents as their physical and chemical properties could be adjusted by a
careful choice of cation and anion. Apart from this, they exhibit acidic
properties. Combining these unique properties of ionic liquids they are
emerging as a ‘green reaction dual-purpose media’ (catalyst + solvent).
The use of ionic liquids as reaction medium may offer a convenient solu-
tion to both the solvent emission and catalytic recycling problem.25−28
RESULTS AND DISCUSSION
In the course of our studies on reactions under solvent-free conditions
and developing new method for transformations of organic functional
groups;29−31 here, we introduce a new and environmentally benign ap-
plication of Bu4N+HSO− as a mild catalyst for protection of carbonyl
functional groups. This 4reagent is a highly chemoselective catalyst for
the conversion of aldehydes in the presence of ketones to the corre-
sponding dithioacetals under solvent-free conditions.
Initially, we tried the protection of aldehydes 1 to the corresponding
dithioacetals 2−by 1,2-ethanedithiol in the presence of catalytic amounts
of Bu4N+HSO4 at room temperature under solvent-free conditions.
This reaction gave dithioacetal derivatives in 73–91% yield after 20–
85 min. The reaction was tried using a wide variety of aldehydes and
ketones containing electron-withdrawing and electron-donating sub-
stituents (Scheme 1, Table I). The reaction proceeds efficiently for car-
bonyl compounds at ambient temperature under mild conditions.
SCHEME 1

2504
Thioacetalization of Aldehydes and Ketones
Moreover, this procedure is highly chemoselective, providing the se-
lective protection of an aldehyde in the presence of a ketone. Treat-
ment of an equimolar mixture of benzaldehyde and acetophenone in
the presence of 1,2-ethanedithiol and catalytic amount of Bu4N+HSO−
(20 mol%) under solvent-free conditions produced only 1,2-dithiolan4e
derivative of benzaldehyde while the acetophenone is completely re-
covered, this competitive reaction illustrating the chemoselectivity of
the present method (Equation (1)). The other competition reactions are
shown in Equations (1–3).

A. R. Hajipour et al.
2505
TABLE I Thioacetalization of Aldehydes and Ketones with
1,2-Ethandithiol Catalyzed by Tetrabutylammonium Hydrogen
Sulfate as an Ionic Liquid
Entry
1
Substrate
C6H5CHO
Product
Time (min)
27
Yield (%)
83
2
3
2-ClC6H5CHO
3-ClC6H5CHO
33
30
79
88
4
5
6
4-ClC6H5CHO
4-O2NC6H5CHO
3-O2NC6H5CHO
26
20
24
90
91
89
7
8
9
4-H3CC6H5CHO
4-MeOC6H5CHO
3-MeOC6H5CHO
29
38
35
82
78
81
(Continued on next page)

2506
Thioacetalization of Aldehydes and Ketones
TABLE I Thioacetalization of Aldehydes and Ketones with
1,2-Ethandithiol Catalyzed by Tetrabutylammonium Hydrogen
Sulfate as an Ionic Liquid (Continued)
Entry
10
Substrate
Product
Time (min) Yield (%)
4-O2NC6H5COCH3
53
84
11
3-O2NC6H5COCH3
51
82
12
13
C6H5COCH3
65
85
76
73
4-MeOC6H5COCH3
14
Cyclobutanone
60
76
aYields refer to pure isolated products and were characterized by comparison of
their physical and spectral data (IR, 1HNMR, m.p., or b.p.) with authentic
samples.31bReactions were carried out in room temperature for aldehydes and at
reflux conditions for ketones.
In summary, we have reported the synthesis of thioacetals and
thioketals using a mild reagent (Bu4N+HSO4−). The reaction of alde-
hydes and ketones having withdrawing groups on their aryl ring to
the corresponding thioacetals and thioketals resulted in corresponding
products in less time and with higher yields.

A. R. Hajipour et al.
2507
EXPERIMENTAL
General
All yields refer to isolated products after purification. All of the products
were characterized by comparison of their spectral (IR, 1H NMR, TLC,
and GC) and physical data (melting or boiling points) with those of
authentic samples.31 All 1H NMR spectra were recorded at 300 MHz in
CDCl3 relative to TMS as an internal standard. All 13C NMR spectra
were recorded at 75 MHz in CDCl3 relative to TMS as an internal
standard. All of the reactions were carried out in a mortar in a hood
with strong ventilation.
Typical Procedure
A solution of benzaldehyde (5 mmol, 0.53 g), 1,2-ethanditiol (7 mmol,
0.65 g), and Bu4N+HSO4− (1 mmol, 0.33 g) in 10 ml dichloromethane
was stirred for 27 min in room temperature, and the reaction was
monitored by TLC. After compilation of the reaction, the solvent was
evaporated via rotary evaporator then 10 ml diethyl ether was added
to the remaining mixture and the solution was washed with NaOH
solution 10% to remove the excess thiol. This solution was dried on
magnesium sulfate and purified via column chromatography.
REFERENCES
[1] (a) H. J. E. Loewenthal, In Protective Groups in Organic Chemistry, J. F. W. McOmie,
Ed. (Plenum Press, New York, 1973), p. 334; (b) T. W. Greene, In Protective Groups
in Organic Synthesis (John Wiley, New York, 1981), pp. 129–133.
[2] (a) E. J. Corey and D. Seebach, J. Org. Chem. 31, 4097 (1966); (b) E. L. Eliel and S.
Morris-Natschke, J. Am. Chem. Soc., 106, 2937 (1984).
[3] (a) D. Seebach, Angew. Chem., Int. Ed. Engl. 8, 639 (1969); (b) B. T. Grobel and D.
Seebach, Synthesis, 357 (1977); (c) P. C. Bulman Page, M. B. Van Niel, and J. C.
Prodger, Tetrahedron, 45, 7643 (1989).
[4] G. R. Pettit and E. E. Van Tamelen, Org. React. 12, 356 (1962).
[5] J. W. Ralls, R. M. Dobson, and B. Reigel, J. Am. Chem. Soc., 71, 3320 (1949).
[6] C. Djerassi and M. Gorman, J. Am. Chem. Soc., 75, 3704 (1953).
[7] (a) L. F. Fieser, J Am. Chem. Soc., 76, 1945 (1954); (b) T. Nakata, S. Nagao, S. Mori,
and T. Oishi, Tetrahedron Lett., 26, 6461 (1985).
[8] B. S. Ong, Tetrahedron Lett., 21, 4225 (1980).
[9] V. Kumar and S. Dev, Tetrahedron Lett., 24, 1289 (1983).
[10] E. J. Corey and K. Shimoji, Tetrahedron Lett., 24, 169 (1983).
[11] L. Garlaschelli and G. Vidari, Tetrahedron Lett., 31, 5815 (1990).
[12] B. Ku and D. Y. Oh, Synth. Commun., 19, 433 (1989).
[13] H. Firouzabadi, N. Iranpoor, and B. Karimi, Synlett, 739 (1998).
[14] B. S.Ong and T. H. Chan, Synth. Commun., 7, 283 (1977).

2508
Thioacetalization of Aldehydes and Ketones
[15] V. G. Saraswathy, V. Geetha, and S. Sankararaman, J. Org. Chem., 52, 4665 (1994).
[16] Y. Kamitori, M. Hojo, R. Masuda, T. Kimura, and T. Yoshida, J. Org. Chem., 52,
1427 (1986).
[17] R. V. Anand, P. Sarvanan, and V. K. Singh, Synlett, 413 (1999).
[18] H. K. Patney and S. Margan, Tetrahedron Lett., 37, 4621 (1996).
[19] S. Chandrasekhar, M. Takhi, Y. R. Reddy, S. Mohapatra, C. R. Rao, and K. V. Reddy,
Tetrahedron, 53, 14997 (1997).
[20] H. K. Patney, Tetrahedron Lett., 35, 5717 (1994).
[21] (a) H. Firouzabadi, N. Iranpoor, and B. Karimi, Synthesis, 58 (1999); (b) M. Tandon
and T. P. Begley, Synth. Commun., 27, 2953 (1997).
[22] (a) J. S. Yadav, B. V. S. Reddy, and S. K. Pandey, Synlett, 238 (2001); (b) B. W. Metcalf,
J. P. Burkhart, and K. Jund, Tetrahedron Lett.,21, 35 (1980).
[23] S. Mathuswamy, S. Arulananda Babu, and C. Gunanathan, Tetrahedron Lett., 42,
359 (2001).
[24] (a) S. Samajdar, M. K. Basu, F. F. Becker, and B. K. Banik, Tetrahedron Lett., 42,
4425 (2001); (b) A. R. Vaino and W. A. Szarek, J. Chem. Soc., Chem. Commun. 2351
(1996).
[25] A. Kamal and G. Chouhan, Synlett, 474 (2002).
[26] A. Kamal and G. Chouhan, Tetrahedron Lett., 43, 1347 (2002).
[27] (a) A. R. Hajipour and N. Mahboubkhah, J. Chem. Research (S), 122 (1998); (b) A.
R. Hajipour and M. Hantehzadeh, J. Org. Chem., 64, 8475 (1999).
[28] (a) I. M. Baltork, A. R. Hajipour and H. Mohammadi, Bull. Chem. Soc. Jpn, 16, 71
(1998); (b) A. R. Hajipour and N. Mahboobkhah, Synth. Commun., 28, 3143 (1998);
(c) A. R. Hajipour and N. Mahboobkhah, J. Chem. Research (S), 122 (1998); (d) A. R.
Hajipour, I. M. Baltork, and G. Kianfar, Bull. Chem. Soc. Jpn, 71, 2655 (1998); (e)
A. R. Hajipour, I. M. Baltork, and G. Kianfar, Indian J. Chem., 37 (B), 607 (1998); (f)
A. R. Hajipour, and N. Mahboobkhah, Org. Prep. Proced. Int., 31, 112 (1999); (g) A.
R. Hajipour, I. M. Baltork, and K. Niknam, Org. Prep. Proced. Int., 31, 335 (1999);
(h) I. M. Baltork, A. R. Hajipour, and R. Haddadi, J. Chem. Research (S), 102 (1999).
[29] A. R. Hajipour and A. E. Ruoho, Org. Prep. Proced. Int., 37, 279 (2005).
[30] A. R. Hajipour, H. Adibi, and A. E. Ruoho, J. Org. Chem., 68, 4553 (2003).
[31] A. R. Hajipour, S. A. Pourmousavi, and A. E. Ruoho, Org. Prep. Proced. Int., 39, 403
(2007).