Chemoselective dithioacetalization and oxathioacetalization of carbonyl compounds using alumina sulfuric acid as catalyst

Article abstract of DOI:10.1080/00397910802272022

Carbonyl compounds have been successfully converted into their corresponding dithiolane, dithiane, and oxathiolane derivatives using a catalytic amount of alumina sulfuric acid (Al2O3-SO3H) with excellent yields at room temperature in short reaction times under mild conditions. This simple method is a highly chemoselective procedure for protection of aldehydes in the presence of ketones, and the heterogeneous catalyst can be recovered and reused several times without any loss of its activity. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802272022

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Chemoselective
Dithioacetalization and
Oxathioacetalization of
Carbonyl Compounds Using
Alumina Sulfuric Acid as
Catalyst
Hamid Reza Shaterian a , Asghar Hosseinian a &
Majid Ghashang a
a Department of Chemistry, Faculty of Sciences,
University of Sistan and Baluchestan, Zahedan, Iran
Version of record first published: 31 Oct 2008
To cite this article: Hamid Reza Shaterian, Asghar Hosseinian & Majid Ghashang
(2008): Chemoselective Dithioacetalization and Oxathioacetalization of Carbonyl
Compounds Using Alumina Sulfuric Acid as Catalyst, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:23,
4097-4106
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Synthetic Communications1, 38: 4097–4106, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802272022
Chemoselective Dithioacetalization and
Oxathioacetalization of Carbonyl Compounds
Using Alumina Sulfuric Acid as Catalyst
Hamid Reza Shaterian, Asghar Hosseinian, and Majid Ghashang
Department of Chemistry, Faculty of Sciences, University of Sistan and
Baluchestan, Zahedan, Iran
Abstract: Carbonyl compounds have been successfully converted into their corre-
sponding dithiolane, dithiane, and oxathiolane derivatives using a catalytic
amount of alumina sulfuric acid (Al2O3–SO3H) with excellent yields at room tem-
perature in short reaction times under mild conditions. This simple method is a
highly chemoselective procedure for protection of aldehydes in the presence of
ketones, and the heterogeneous catalyst can be recovered and reused several times
without any loss of its activity.
Keywords: 1,3-dithiane, 1,3-dithiolane, 1,3-oxathiolane, Alumina sulfuric acid,
dithioacetalization, heterogeneous catalyst
INTRODUCTION
Organic synthesis involving heterogeneous and recyclable catalysts has
been investigated worldwide, keeping in mind the stringent environment
and economic regulations.[1] Homogeneous catalysts such as H2SO4, HF,
HBr, HCl, CF3COOH, and complexes of BF3 are frequently used in
organic synthesis.[2] However, processes involving conventional acids
are inherently associated with problems such as high toxicity, catalyst
waste, and corrosive and polluting reagents. In homogeneous reaction
Received April 12, 2008.
Address correspondence to Hamid Reza Shaterian, Department of Chemistry,
Faculty of Sciences, University of Sistan and Baluchestan, P.O. Box 98135-674,
Zahedan, Iran. E-mail: hrshaterian@hamoon.usb.ac.ir
4097

4098
H. R. Shaterian, A. Hosseinian, and M. Ghashang
conditions, the catalyst is difficult to recover, reuse, and separate from
the reaction mixture.[3] Replacement of these conventional acids by a
solid heterogeneous catalyst is desirable to achieve effective catalyst
handling, product purification, and decreased waste production.[3,4] The
protection of carbonyl groups as dithioacetals is a common and popular
practice in organic chemistry[5] as they are quite stable under basic or
acidic conditions.[6] The dithioacetals in the form of 1,3-dithiolanes and
1,3-dithianes are also utilized as masked acyl anion[7–9] or masked methy-
lene functions[10] in carbon–carbon bond-forming reactions and also pro-
tect the carbonyl groups against an attack by various reagents such as
nucleophiles, oxidants, and hydride reducing agents. Dithioacetals are
prepared by condensation of carbonyl compounds with thiols in the pre-
sence of Brønsted and Lewis acid catalysts such as LiBF4,[11] Bi(OTf)3,[12]
SO2,[13] Sc(OTf)3
InCl3,[15] CoCl2,[16] NiCl2,[17] MoO2(acac)2,[18]
[14]
Y(OTf)3,[19] p-toluenesulfonic acid,[20] LiBr,[21] and silica sulfuric acid.[22]
Many of these methods require long reaction times,[11,12] reflux condi-
tions,[12] the use of expensive reagents,[12] and stoichiometric amounts
of catalyst.[13] Although some Lewis acid catalysts have been reported
to show chemoselectivity, these catalysts are destroyed in the workup
procedure and cannot be recovered and reused.[15,20] Some methods failed
to protect deactivated aromatic substrates.[14] Therefore, there is still a
need to develop a simple and efficient method for dithioacetalization of
carbonyl groups and chemoselective protection of aldehydes in the
presence of ketones using catalysts that could be superior to the existing
ones with regards to toxicity, handling, and recyclability.
In continuation of our interest to develop application of heteroge-
neous catalysts in organic chemistry transformations,[23,24] herein we
report an efficient method for the dithioacetalization and oxathioacetali-
zation of carbonyl compounds as well as the chemoselective protection of
various carbonyl compounds by employing Al2O3–SO3H as catalyst
(Scheme 1).
Sulfuric acid supported on alumina as inorganic solid compound was
prepared according to silica sulfuric acid.[25,26] Alumina sulfuric acid as a
Scheme 1. Dithioacetalization and oxathioacetalization of carbonyl compounds
using alumina sulfuric acid as catalyst.

Dithioacetalization and Oxathioacetalization
4099
heterogeneous solid Brønsted acid catalyst is safe, easy to handle,
environmentally benign, and presents fewer disposal problems.
RESULTS AND DISCUSSION
To choose optimal conditions, first we tried to prepare 2-phenyl-1,3-
dithiane in the reaction of 1,3-propanedithiol (1.05 mmol) with benzalde-
hyde (1 mmol) in the presence of a different amount of alumina sulfuric
acid in different solvents (2 mL) (Table 1).
As can be seen from Table 1, the best results were obtained using
50 mg of catalyst. Among these solvents acetonitrile was the solvent
of choice in terms of time and product yield (Table 1). Thus, we prepared
a range of dithiolane, dithiane, and oxathiolane derivatives under
the optimized reaction conditions: aldehydes or ketones (1 eq);
1,3-propandithiol, 1,2-ethanedithiol, or 2-mercaptoethanol (1.05 eq);
and acetonitrile (as solvent, 2 mL) in the presence of alumina sulfuric acid
(50 mg) (Table 2). Interestingly, the experimental procedure for these
reactions is very simple and does not need the use of dry solvents or inert
atmospheres. A catalytic amount of heterogeneous Al2O3–SO3H as cata-
lyst is sufficient to obtain the desired compounds in excellent yields
(Scheme 1).
As shown in Table 2, several different aliphatic or aromatic alde-
hydes with both electron-withdrawing and donating substituents pro-
duced corresponding cyclic dithioacetal without the formation of any
side products, in high to excellent yields and short reaction times at room
Table 1. Conversion of benzaldehyde (1 mmol) to 2-phenyl-1,3-dithiane using 1,3-
propanedithiol (1.05 mmol) in the presence of different amounts of solid alumina
sulfuric acid as catalyst under a variety of solvents (2 mL) at room temperature
Entry
Solvent
Catalyst (mmol)
Time
GC yield (%)
1
2
3
4
5
6
7
8
9
10
Diethyl ether
Dichloromethane
Ethylacetate
Chloroform
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
0.1
0.1
0.1
0.1
0.2
0.1
0.05
0.02
0.01
0
2 h
19.5 h
13.5 h
15.5 h
3.7 min
5 min
6 min
20 min
1 h
100
100
100
100
100
100
100
98
96
—
20 h

4100

4101

4102
H. R. Shaterian, A. Hosseinian, and M. Ghashang
temperature (Table 2, entries 1–14). In addition, this catalyst is able to
protect carbonyl compounds using 2-mercaptoethanol and produce cor-
responding 1,3-oxathiolanes in excellent yields under ambient conditions
(Table 2, entries 21–23).
The reaction of cyclohexanone with 1,3-propanedithiol was com-
pleted after 120 min at room temperature (Table 2, entry 15); to decrease
reaction time, we performed this reaction at 80 ꢀC in an oil bath (Table 2,
entry 15, time ¼ 25 min). In continuation of this work, we performed
dithioacetalization reactions with aromatic and aliphatic ketones under
reflux conditions (Table 2, entries 15–20). Transthioacetalization of ben-
zaldehyde and acetophenone oximes, in the reaction conditions (rt, 0.05 g
catalyst, and acetonitrile as solvent) did not give the desired product
(Table 2, entries 24–27). It is noteworthy that aromatic or acyclic
aliphatic ketones did not undergo the reaction at room temperature. This
result prompted us to explore the chemoselective protection of aldehydes
in the presence of ketones. For instance, when an equimolar mixture of
aldehyde and ketone was allowed to react with dithiol in the presence
of a catalytic amount of Al2O3–SO3H, only the 1,3-dithiane derivative
of the corresponding aldehyde was obtained, whereas ketone was recov-
ered quantitatively (Table 3, entries 1–3). Thus, the catalyst can promote
dithioacetalization and oxathiaoacetalaization in a rapid, mild, and selec-
tive manner.
The reusability of the catalysts is one of the most important benefits.
Thus, the recovery and reusability of Al2O3–SO3H were investigated. In a
typical experiment, after the reaction was completed, in the workup stage,
solution was filtrated and the catalyst was isolated from the reaction
mixture. The purified catalyst was achieved by washing the solid residue
catalyst with dichloromethane and followed by drying in an oven at
100 ꢀC for 30 min. In every experiment, more than 98% of the catalyst
was easily recovered from the reaction mixture. Catalytic activity of the
recovered catalyst was tested at least five times and showed activity the
same as alumina sulfuric acid that was used for the first time (Table 2,
entry 1).
To show the merit of the present work in comparison with reported
results in the literature, we observed that the alumina-supported catalyst
was much more effective than other catalysts derived from transition
metals and related elements.[16–19,22]
CONCLUSION
In conclusion, we demonstrated that alumina sulfuric acid is a new, effi-
cient, mild, and heterogeneous catalyst for dithioacetalization and

Dithioacetalization and Oxathioacetalization
4103
Table 3 Selective dithioacetalization of different aldehydes and ketones
Time
(min)
Yield
(%)a,b
Entry
Aldehyde and ketone
Products
100
1
3
0
100
2
10
0
100
3
6
0
aGC yield using n-octane as internal standard.
bThe molar ratio of substrate 1=substrate 2=1,3-propanedithiol=catalyst was
chosen 1=1=1.05=0.05 (g).
oxathioacetalization of various aldehydes and ketones at room tempera-
ture. This simple and efficient method is a highly chemoselective proce-
dure for protection of aldehydes in the presence of ketones. Alumina
sulfuric acid can be recovered from reaction mixtures and reused at there
reaction conditions.

4104
H. R. Shaterian, A. Hosseinian, and M. Ghashang
EXPERIMENTAL
All reagents were purchased from Merck and Aldrich and used without
further purification. Alumina sulfuric acid was prepared according to the
reported procedure.[25] All yields refer to isolated products after purifica-
tion. The products were characterized by comparison with those of the
authentic samples of the spectroscopy data (IR, 1H NMR, 13C NMR spec-
tra). The NMR spectra were recorded on a Bruker Avance DEX 300-MHz
instrument in CDCl3 relative to TMS (0.00 ppm). IR spectra were recorded
on a Perkin-Elmer 781 spectrophotometer. Thin-layer chromatography
(TLC) was performed on silica-gel polygram SIL G=UV 254 plates.
General Procedure for the Dithioacetalization and Oxathioacetalization
of Carbonyl Compounds
The carbonyl compound (1 mmol), 1,2-ethanedithiol, 1,3-propanedithiol
(1.05 mmol) or 2-mercaptoethanol (1.05 mmol), and Al2O3–SO3H as cata-
lyst (50 mg, 0.15 mmol of Hþ)[26] were combined together in acetonitrile
(2 mL). The reaction mixture was stirred at room temperature. Completion
of the reaction was indicated by TLC or gas chromatography (GC). After
completion of the reaction, acetonitrile was evaporated from the reaction
mixture. The reaction mixture was combined with dichloromethane and
filtered. The catalyst washed with dichloromethane and then dried; the
recovered catalyst can be used again. The organic layer was extracted with
10% sodium hydroxide solution (10 ml) followed by a water (10 ml) and
brine solution (5 ml). The organic layer was dried with anhydrous sodium
sulfate and filtered, the solvent was evaporated under reduced pressure,
and the pure product was obtained. All the desired pure product(s) were
characterized by comparison of their physical data with those of the
known the dithioacetals and oxothioacetals.[11–22] The spectral data of
2-phenyl-1,3-dithiane (Table 2, entry 1) is given here: mp ¼ 68–70ꢀC
(lit.[21] 71–72); 1H NMR (CDCl3, 300 MHz): d ¼ 1.92–1.96 (m, 1H),
2.15–2.17 (m, 1H), 2.88–3.10 (m, 4H), 5.17 (s, 1H), 7.29–7.48 (m, 5H)
ppm; 13C NMR (CDCl3, 75 MHz): d ¼ 24.73, 31.01 (2C), 50.00, 127.49
(2C), 128.22, 128.64 (2C), 139.54 ppm; IR (KBr, cmꢁ1): 3063, 3022,
2929, 2894, 1685, 1598, 1487, 1445, 1429, 1276, 1240, 1158, 1071, 845, 698.
ACKNOWLEDGMENTS
We are thankful to the Sistan and Baluchestan University Research
Council for the partial support of this research.

Dithioacetalization and Oxathioacetalization
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