Aluminum hydrogen sulfate [Al(HSO4)3] as an efficient catalyst for the preparation of thioacetals

Article abstract of DOI:10.1007/s11164-012-0802-8

Aluminum hydrogen sulfate, as a heterogeneous solid acid catalyst, has been used for the mild conversion of carbonyl compounds to their thioacetals using 1,2- and 1,3-dithiol under ambient conditions with short reaction times in high to excellent yield in

Full text of DOI:10.1007/s11164-012-0802-8

Res Chem Intermed (2013) 39:2837–2842
DOI 10.1007/s11164-012-0802-8
Aluminum hydrogen sulfate [Al(HSO4)3] as an efficient
catalyst for the preparation of thioacetals
Majid Ghashang
Received: 25 June 2012 / Accepted: 31 August 2012 / Published online: 18 September 2012
Ó Springer Science+Business Media B.V. 2012
Abstract Aluminum hydrogen sulfate, as a heterogeneous solid acid catalyst, has
been used for the mild conversion of carbonyl compounds to their thioacetals using
1,2- and 1,3-dithiol under ambient conditions with short reaction times in high to
excellent yield in acetonitrile as solvent.
Keywords Aluminum hydrogen sulfate [Al(HSO4)3] Á Thioacetals Á
Thioacetalization Á C–S bond formation Á Carbonyl compounds
Introduction
Protection and de-protection of functional groups play an important role in many
organic synthetic transformations. Thiols are groups of chemical compounds which
used as protecting groups for carbonyl compounds in organic synthesis [1]. In this
content, thioacetals, dithioacetals and oxathioacetals are some of the useful
compounds in organic synthesis introduced from thiols and carbonyl compounds.
These compounds are applicable as building blocks for the synthesis of acyl
carbanions. They behave as blocking groups which are applicable for electrophilic
substitution on the carbonyl compound. Thioacetals are stable under usual acidic or
basic conditions [2–5]. Using this beneficial view of thioacetals, numerous methods
have been reported for the preparation of thioacetals via condensation of carbonyl
compounds with thiols or dithiols including the use of Lewis or Brønsted acid
catalysts either solitarily or supported on solid materials, e.g. silica and alumina and
some silicon reagents [6–32].
M. Ghashang (&)
Department of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University,
P.O. Box 517, Najafabad, Esfaha¯n, Iran
e-mail: ghashangmajid@gmail.com
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M. Ghashang
Although the disadvantages of homogeneous catalysts, such as harsh conditions,
poor selectivity and yields, and also the toxicity and expense of some metal
compounds, have been overcome by the use of heterogeneous catalysts and
supported reagents, developments in this area demand further searches for better
catalysts that could be superior to the existing ones with regard to toxicity, handling,
selectivity, and recyclability. In this respect, we are interested in introducing
aluminum hydrogen sulfate Al(HSO4)3 [33–38] as an efficient catalyst for the
protection of carbonyl compounds and the preparation of thioacetals to overcome
these limitations (Scheme 1).
This protocol reports an atom-economical synthesis of a variety of thioacetals
from the reaction of carbonyl compounds and thiols using Al(HSO4)3 as catalyst and
acetonitrile as solvent.
Results and discussion
First, the synthesis of 2-phenyl-1,3-dithiane was chosen as a model to find an
appropriate solvent. Various common organic solvents such as n-Hexane, CH2Cl2,
Et2O, EtOAc, EtOH, CH3CN and also solvent-free condition were examined. The
results are summarized in Table 1. It can be seen that the reaction using CH3CN as
solvent resulted in excellent yield and the shortest time. Therefore, CH3CN was
chosen as the solvent of this reaction (Table 1, Entry 6).
To optimize the catalyst loading, 0.075, 0.15, 0.3, 0.6, and 0.8 mmol of
Al(HSO4)3 were tested, respectively. The results are summarized in Table 1. A
0.15-mmol loading of the catalyst was sufficient to promote the reaction (Table 1,
Entry 6). No significant improvement in the yields was observed on further
increasing the catalyst loading.
With optimized experimental conditions (Table 1), the generality of this process
has been investigated with a wide range of aromatic, aliphatic and heterocyclic
aldehydes, and also ketones, in the presence of catalytic amounts of Al(HSO4)3;
the results are shown in Table 2. The various types of aromatic aldehydes with
electron-donating and electron-withdrawing groups were converted to the corre-
sponding dithianes and dithiolanes in the presence of 0.15 mmol of Al(HSO4)3
S
S
Ar
H(CH3)
Al(HSO4)3
Ar
O
+ R-SH
CH3CN; r.t.
H(CH3)
H(CH3)
S
Ar
S
SH
SH
R =
SH SH
Scheme 1 Synthesis of dithianes and dithiolanes
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Efficient catalyst for the preparation of thioacetals
2839
Table 1 Optimization of the
reaction conditions in the
synthesis 2-phenyl-1,3-dithiane
Entry
Catalyst
(mmol)
Solvent
(5 ml)
Time
(min)
Yield
(%)a
1
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.075
0.3
n-Hexane
CH2Cl2
Et2O
30
15
45
50
50
4
20b
75
55b
45b
39b
95
2
3
4
EtOAc
EtOH
5
6
CH3CN
–
7
20
1
25
a
8
CH3CN
CH3CN
CH3CN
CH3CN
91
Isolated yields, reaction
condition: room temperature
9
1
90
b
Separated by the using of plate
chromatography due to
incomplete conversions
10
11
0.6
1
91
0.8
1
89
(Table 2, Entries 1–27). Butyraldehyde and ethyl 3-oxobutanoate were effectively
protected in good yields (Table 2, Entries 28–29). The protection of furfural as a
heteroaromatic aldehyde was also carried out under similar reaction conditions
(Table 2, Entry 30).
In general, aldehydes react much faster than ketones with thiols and the reaction
of acetophenone and its derivatives with 1,3-propanedithiol were not completed at
room temperature; thus, we performed these reactions at 80 °C in an oil bath
(Table 2, Entries 31–34).
The chemo-selectivity of this procedure was examined via the reaction of an
equimolar mixture of benzaldehyde and acetophenone with propane-1,3-dithiol
under ambient condition. It is noteworthy that acetophenone did not produce the
corresponding thioacetals under the same reaction conditions (Scheme 2).
The reusability of Al(HSO4)3 was examined in the preparation of 2-phenyl-1,3-
dithiane, as shown in Fig. 1. The catalyst was recovered after each run, washed
three times with CH2Cl2, dried prior to use, and tested for its activity in the
subsequent run; fresh catalyst was not added. The catalyst was tested for 10 runs. It
was seen that the catalyst displayed very good reusability.
In summary, this protocol has a generally applicable, mild, cost-effective,
operational and convenient procedure for the chemo-selective protection of
carbonyl compounds as thioacetals, where the catalyst could be readily recovered
and reused. It was found that a wide range of carbonyl compounds react with excess
thiols to give dithianes and dithiolanes in the presence of Al(HSO4)3 under ambient
conditions using acetonitrile as solvent.
Experimental
All reagents were purchased from Merck and Aldrich and used without further
purification. All yields refer to isolated products after purification. The NMR spectra
123

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M. Ghashang
Table 2 Thioacetalization of carbonyl compounds using Al(HSO4)3 as catalyst under ambient condition
(Scheme 1)
Entry
Aldehyde
Thiol
Time (min)
Yield (%)a
1
Benzaldehyde
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Ethane-1,2-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
Propane-1,3-dithiol
4
3
95
97
94
90
89
94
85
92
96
90
88
87
76
90
94
93
84
89
82
93
84
89
95
93
81
82
74
89
81
81
88b
91b
90b
89b
2
4-Methylbenzaldehyde
2-Methylbenzaldehyde
4-Methoxybenzaldehyde
2-Methoxybenzaldehyde
4-Chlorobenzaldehyde
2-Chlorobenzaldehyde
2,4-Dichlorobenzaldehyde
4-Bromobenzaldehyde
4-Fluorobenzaldehyde
4-Nitrobenzaldehyde
3-Nitrobenzaldehyde
2-Nitrobenzaldehyde
Cinnamaldehyde
3
5
4
3
5
5
6
7
7
11
15
8
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
a
7
30
25
67
7
Benzaldehyde
5
4-Methylbenzaldehyde
2-Methylbenzaldehyde
4-Methoxybenzaldehyde
2-Methoxybenzaldehyde
4-Chlorobenzaldehyde
2-Chlorobenzaldehyde
2,4-Dichlorobenzaldehyde
4-Bromobenzaldehyde
4-Fluorobenzaldehyde
4-Nitrobenzaldehyde
3-Nitrobenzaldehyde
2-Nitrobenzaldehyde
Butyraldehyde
4
9
4
10
9
17
21
9
9
40
37
70
9
Ethyl 3-oxobutanoate
Furfural
10
12
11
10
15
45
Acetophenone
1-(4-Methoxyphenyl)ethanone
1-(4-Chlorophenyl)ethanone
1-(4-Nitrophenyl)ethanone
Isolated yields
b
The reaction was performed at 80 °C under reflux conditions
were recorded on a Bruker Avance DPX 400 MHz instrument. The spectra were
measured in CDCl3 relative to TMS (0.00 ppm). TLC was performed on silica gel
polygram SIL G/UV 254 plates.
123

Efficient catalyst for the preparation of thioacetals
2841
Al(HSO4)3
(0.15 mmol)
Ph
O
+
+
S
S
H
S
S
CH3CN; r.t.
SH SH
H(CH3)
Ph
Ph
CH3
94%
0%
Scheme 2 Chemo-selective preparation of 2-phenyl-1,3-dithiane
Fig. 1 Reusability of Al(HSO4)3
General procedure for the preparation of dithianes and dithiolanes
To a mixture of a carbonyl compound (1 mmol) and 1,3-propanedithiol or 1,2-
ethanedithiol (1.2 mmol) in acetonitrile (2 ml) was added 0.15 mmol of Al(HSO4)3.
The reaction mixture was stirred at room temperature for the time indicated in
Table 2. The progress of the reaction was monitored by TLC or GC. After
completion of the reaction, acetonitrile was evaporated from the reaction mixture.
The reaction mixture was combined with dichloromethane and filtered. The organic
layer was extracted with 10 % NaHCO3 solution (10 ml) followed by water (10 ml)
and brine solution (5 ml). Organic layer dried with anhydrous CaCl2 and filtered,
the solvent was evaporated under reduced pressure, and the pure product was
obtained.
Acknowledgment The authors are indebted to the Islamic Azad University, Najafabad Branch for
financial support of this research.
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