Highly efficient and chemoselective method for the thioacetalization of aldehydes and transthioacetalization of acetals and acylals catalyzed by H 2SO4-silica under solvent-free conditions

Article abstract of DOI:10.1007/s00706-011-0664-6

Chemoselective and efficient thioacetalization of a variety of aldehydes was achieved in excellent yields at room temperature using 1,2-ethanedithiol in the presence of catalytic amounts of H₂SO₄-silica. Thioacetals were also prepare

Full text of DOI:10.1007/s00706-011-0664-6

Monatsh Chem (2012) 143:917–923
DOI 10.1007/s00706-011-0664-6
ORIGINAL PAPER
Highly efficient and chemoselective method for the thioacetalization
of aldehydes and transthioacetalization of acetals and acylals
catalyzed by H2SO4-silica under solvent-free conditions
•
Seied Ali Pourmousavi Shaghayegh Sadat Kazemi
Received: 15 March 2011 / Accepted: 25 September 2011 / Published online: 9 November 2011
Ó Springer-Verlag 2011
Abstract Chemoselective and efficient thioacetalization
of a variety of aldehydes was achieved in excellent yields
at room temperature using 1,2-ethanedithiol in the presence
of catalytic amounts of H2SO4-silica. Thioacetals were also
prepared by transthioacetalization of acylals and acetals
under similar conditions.
using a heterogeneous catalyst. On the other hand,
although some of these methods have convenient proto-
cols with good to high yields, the majority of these
methods have certain disadvantages such as long reaction
times, reflux conditions, stoichiometric amount of cata-
lyst, and the use of expensive and toxic catalysts.
Consequently, it is necessary to develop alternative
methods for the chemoselective thioacetalization of
aldehydes.
Keywords Thioacetalization Á Transthioacetalization Á
Aldehydes Á Chemoselectivity Á Solvent free Á Acetal Á
Acylal
Results and discussion
Introduction
In the course of our studies on reactions under solvent-free
conditions [18–20] and noting recent reports on the use of
H2SO4-silica in various organic transformations [21–25],
here we introduce a highly chemoselective, efficient, and
fast method for the preparation of thioacetals in the pres-
ence of silica-supported sulfuric acid (H2SO4-silica). In this
method thioacetalization of aldehydes and transthioacetal-
ization of acylals and acetals have been investigated in the
presence of 1,2-ethanedithiol and a catalytic amount of
H2SO4-silica at ambient temperature under solvent-free
conditions (Scheme 1). To the best of our knowledge,
H2SO4-silica has not been used for thioacetalization or
transthioacetalization.
Protection of carbonyl groups as thioacetals is quite often
a necessary requirement in the synthesis of multiple
functional organic molecules [1, 2]. This is because of
their stability both in acidic and basic conditions. In
general, these compounds are prepared by protic or Lewis
acid catalyzed condensation of carbonyl compounds with
thiols or dithiols [3–12]. Among many of the recently
developed catalysts, solid supported catalysts such as
FeCl3-SiO2 [13], ZrCl4-SiO2 [14], SOCl2-SiO2 [15],
Cu(OTf)2-SiO2 [16], and glycerol [17] are of choice for
this purpose because of easier handling, mildness of the
reaction conditions, and simple workup procedures.
However, literature survey shows that only a few of these
methods are available for the chemoselective protection
of aldehydes in the presence of ketones especially by
To choose the most appropriate medium for the thio-
acetalization reaction, we examined the protection of
benzaldehyde as the model compound with 1,2-ethanedi-
thiol using H2SO4-silica in various solvents and under
solvent-free conditions (Table 1). The solvents examined
were ethyl acetate, dichloromethane, acetonitrile, and
n-hexane. The reactions were carried out by stirring
benzaldehyde with 0.02 g H2SO4-silica and 1.2 equiv. of
1,2-ethanedithiol at room temperature.
S. A. Pourmousavi (&) Á S. S. Kazemi
School of Chemistry, Damghan University,
36715364 Damghan, Iran
e-mail: pourmousavi@du.ac.ir
123

918
S. A. Pourmousavi, S. S. Kazemi
out under similar reaction conditions (Table 2, entries 11,
12, and 13).
X
X
O
H2SO4-silica
S
S
or
R2
R1
R2
This protocol was not effective for ketones as exem-
plified by entry 16 in Table 2. This result prompted us to
explore the chemoselective protection of aldehydes in the
presence of ketones. For example, when an equimolar
mixture of benzaldehyde and acetophenone was allowed to
react with 1,2-ethanedithiol in the presence of a catalytic
amount of H2SO4-silica, only the dithioacetal derivative of
benzaldehyde was obtained. The competition reactions are
shown in Scheme 3.
R1
HSCH2CH2SH
R1 R2
R1, R2 = Alkyl, H, or aryl
X = OAc, -O-CH2C(CH3)2CH2-O-
Scheme 1
Table 1 Thioacetalization of benzaldehyde catalyzed by H2SO4-sil-
ica under various solvent and solvent-free conditions
Dithioacetals are quite stable toward a variety of
reagents, including acidic ones, while acetals are not suit-
able for being handled in an acidic environment. Due to
their stability, transthioacetalization of acetals and acylals
to dithioacetals is a synthetically useful transformation and
is usually carried out under the catalysis of a variety of
Lewis acids such as InCl3 [26], MgBr2 [27], WCl6 [28], ZrCl4
[29], trichloroisocyanuric acid [30], SiO2-SOCl2 [31], and I2
[32]. The results obtained in the case of thioacetalization
prompted us to study the transthioacetalization of acetals and
acylals using H2SO4-silica at room temperature. Accordingly,
acetals and acylals were reacted with 1,2-ethaneditiol in the
presence of 0.05 g H2SO4-silica (Scheme 4), and it was found
that the thioacetals were obtained in high isolated yields
(Table 3).
O
S
S
H
H2SO4-silica (0.02 g)
H
HSCH2CH2SH (1.2 mmol)
Solvent
1 mmol
Entry
Solvent
Time
Yield/%a
1
2
3
4
5
a
Dichloromethane
Acetonitrile
Ethyl acetate
n-Hexane
16 h
20
100
90
14 min
16 h
16 h
10
No solvent
2 min
96
Yields refer to isolated pure product
In conclusion, the present H2SO4-silica catalyzed pro-
cedure provides a highly efficient methodology for the
chemoselective thioacetalization of aldehydes and trans-
thioacetalization of acetals and acylals under solvent-free
conditions. The significant advantages of this procedure
are: (1) solvent-free conditions, (2) high yields, (3) fast
reaction, (4) general applicability to a various aldehydes,
acetals, and acylals, (5) operational simplicity, (6) che-
moselectivity, and (7) H2SO4-silica is an inexpensive,
easily available, and environmentally benign solid support
acid. Thus, it offers a better and more practical alternative
to the existing methodologies.
O
H2SO4-silica (0.02 g)
S
R
S
H
HSCH2CH2SH (1.2 mmol)
Solvent free
R
H
1 mmol
R = Alkyl, aryl
Scheme 2
As shown in Table 1, in comparison to conventional
methods in solution, the yield of the reaction under solvent-
free conditions is higher and the reaction time is shorter. It
should be pointed out that in the absence of H2SO4-silica,
the reaction did not proceed even after prolonged reaction
times. In a typical procedure, the reaction of 1 mmol
benzaldehyde with 1.2 mmol 1,2-ethanedithiol in the
presence of 0.02 g H2SO4-silica at r.t. under solvent-free
conditions afforded the desired dithioacetal in 96% yield.
The versatility of the process has been proved with a wide
range of aldehydes containing electron-withdrawing and
electron-donating substituents (Scheme 2). The results of
the thioacetalization of various aldehydes are shown in
Table 2.
Experimental
Preparation of H2SO4-silica [25], acylals [25], and acetals
[33] was carried out according to previously reported
methods. Yields refer to isolated pure products. All the
products were characterized by their 1H NMR and IR
spectra, and identified by comparison of their physical and
spectral data with the well-known compounds [19, 34, 35].
1
All H NMR spectra were recorded at 500 MHz in CDCl3
relative to TMS (0.00 ppm). IR spectra were recorded on a
Perkin-Elmer Spectrum RX I FT-IR spectrophotometer.
Thin layer chromatography was performed on silica SIL
G/UV 254 plates.
Various aldehydes gave dithioacetal derivatives in
74–98% yields after 2–17 min. The protections of hetero-
aromatic and a,b-unsaturated aldehydes were also carried
123

Highly efficient and chemoselective method
919
Table 2 Thioacetalization of aldehydes in the presence of 0.02 g H2SO4-silica
Entry
1
Substrate
Product
Time/min
3
Yield/%
96
O
S
S
H
H
2
14
74
O
S
S
H
H
O2N
O2N
3
4
5
6
94
94
O
S
S
H
H
OMe
O
OMe
S
S
H
H
Me
Me
5
6
2
5
98
98
O
S
S
Ph
H
Ph
H
O
S
S
MeO
MeO
MeO
MeO
H
H
OMe
OMe
S
7
8
98
O
S
H
H
MeO
MeO
OMe
O
OMe
S
8
10
89
S
H
H
NO2
NO2
123

920
S. A. Pourmousavi, S. S. Kazemi
Table 2 continued
Entry
Substrate
Product
Time/min
Yield/%
97
9
4
O
S
S
H
H
MeO
MeO
10
2
97
O
S
S
H
H
MeO
OMe
MeO
OMe
11
12
17
98
96
H
H
O
O
S
S
O
9
O
S
S
Ph
H
Me
Ph
Ph
H
Me
S
13
14
4
95
76
O
S
Ph
H
H
16
O
S
S
H
H
NO2
NO2
15
16
5
94
O
S
S
H
H
HO
HO
10
5
O
S
S
CH3
CH3
The yields refer to isolated pure products
1
The products were characterized from their spectral data (IR and H NMR) and comparison with authentic samples
123

Highly efficient and chemoselective method
921
O
H
S
S
X
X
S
H
H2SO4-silica (0.05 g)
S
S
R1
R2
HSCH2CH2SH (1.2 mmol)
R1 R2
100%
1 mmol
1 mmol
H2SO4-silica (0.02 g)
HSCH2CH2SH (1.2 mmol)
O
R1, R2 = Alkyl, H, or aryl
S
Solvent free
5 min
CH3
0%
CH3
X = OAc, -O-CH2C(CH3)2CH2-O-
1 mmol
Scheme 4
S
S
H
O
H
silica as a free-flowing powder (2.95 mg = 0.01 mmol of
80%
H2SO4).
O2N
H2SO4-silica (0.02 g)
O2N
1 mmol
O
HSCH2CH2SH (1.2 mmol)
Solvent free
S
General procedure for the thioacetalization
of aldehydes, acetals, and acylals by H2SO4-silica
S
15 min
CH3
CH3
O2N
0%
A mixture of aldehyde or acetal (acylal) (2 mmol), 1,2-
ethanedithiol (2.4 mmol), and 0.02–0.05 g H2SO4-silica in
a mortar was ground with a pestle for the time specified in
Table 2. The progress of the reaction was monitored
by TLC using ethyl acetate/cyclohexane 15:85 as eluent.
After completion of the reaction, the mixture was washed
with CH2Cl2 (4 3 10 cm3) and filtered. Evaporation of
the solvent under reduced pressure gave the almost pure
thioacetal. Further purification was done by preparative
O2N
1 mmol
Scheme 3
Preparation of H2SO4-silica
In a mortar 2 g silica gel (0.063–0.2 mm) and 1 g H2SO4
(98%, 10 mmol) were ground with a pestle, and the residue
was heated at 100 °C for 12 h to furnish 2.95 g H2SO4-
Table 3 Transthioacetalization of acetals and acylals in the presence of 0.05 g H2SO4-silica
Entry
1
Substrate
Product
Time/min
5
Yield/%a
94
S
S
H
O
O
H
MeO
MeO
2
7
92
S
S
H
O
O
H
OMe
OMe
3
5
97
S
S
O
O
H
Ph
H
Ph
123

922
S. A. Pourmousavi, S. S. Kazemi
Table 3 continued
Entry
Substrate
Product
Time/min
15
Yield/%a
80
4
S
S
H
O
O
H
O2N
O2N
5
4
98
S
S
O
O
H
Ph
H
Ph
6
7
9
2
90
96
AcO
OAc
S
S
H
H
AcO
OAc
H
S
S
H
MeO
MeO
OMe
OMe
S
8
9
6
8
91
97
AcO
OAc
S
H
H
OMe
OMe
AcO
OAc
H
S
S
Ph
Ph
H
The yields refer to isolated pure products
a
1
The products were characterized from their spectral data (IR and H NMR) and comparison with authentic samples
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Acknowledgments We are grateful to Damghan University (grant
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