Silica gel-supported polyphosphoric acid (PPA/SiO2) as an efficient and reusable catalyst for conversion of carbonyl compounds into oxathioacetals and dithioacetals

Article abstract of DOI:10.1055/s-2004-832812

A simple and efficient method for the conversion of carbonyl compounds to oxathioacetals and dithioacetals by using polyphosphoric acid supported on silica gel (PPA/SiO₂) as an acid catalyst have been developed. PPA/SiO₂ is easily re

Full text of DOI:10.1055/s-2004-832812

LETTER
2307
Silica Gel-Supported Polyphosphoric Acid (PPA/SiO2) as an Efficient
and Reusable Catalyst for Conversion of Carbonyl Compounds into
Oxathioacetals and Dithioacetals
Conversionof
C
a
arbonyl
C
d
ompounds in
a
toOxathioa
s
cetals and
h
D
ithioaceta
i
ls Aoyama,*a Toshio Takido,a Mitsuo Kodomarib
a
Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, Kanda Surugadai, Chiyoda-ku,
Tokyo 101-8308, Japan
b
Department of Applied Chemistry, Shibaura Institute of Technology, Shibaura, Minato-ku, Tokyo 108-8548, Japan
Fax +81(3)32590818; E-mail: aoyama@chem.cst.nihon-u.ac.jp
Received 30 June 2004
catalyst for the synthesis of dithioacetals. However,
dithioacetalyzation using this catalyst requires drastic
conditions, and the preparation of the catalyst is difficult
and takes a lot of time, and it is sensitive to moisture.
Abstract: A simple and efficient method for the conversion of car-
bonyl compounds to oxathioacetals and dithioacetals by using poly-
phosphoric acid supported on silica gel (PPA/SiO2) as an acid
catalyst have been developed. PPA/SiO2 is easily recovered from
the reaction mixture and reused without a decrease in catalytic Polyphosphoric acid (PPA) has been used as a protic acid
activity.
catalyst for organic reactions. Although there are many re-
ports using PPA16 as a catalyst for organic reactions, PPA
Key words: oxathioacetals, dithioacetals, protecting groups,
polyphsphoric acid, silica gel
is difficult to handle because of viscous liquid at room
temperature. The reagent supporting PPA onto silica gel
(PPA/SiO2) has been used for the oligomerization of low-
er olefins17 and for other applications. However, there are
few reports using PPA/SiO2 for organic synthesis. PPA/
SiO2, which is easy to prepare and to handle, is a very use-
ful acid catalyst and could be removed only by filtration
from the reaction mixture and has long working life. In
this report, we wish to introduce a simple and efficient
method for the conversion of carbonyl compounds into
oxathioacetals and dithioacetals using PPA/SiO2.18 Oxa-
thioacetals and dithioacetals were obtained in excellent
yields from the reaction of various aliphatic and aromatic
aldehydes containing electron-donating and withdrawing
groups with mercaptoethanol or 1,2-ethanedithiol in the
presence of PPA/SiO2 under mild conditions. Aliphatic
ketones were also oxathioacetalized and dithioacetalized
in the presence of PPA/SiO2. In these reactions, PPA/SiO2
serves as a water scavenger as well as an acid catalyst
(Scheme 1).
The protection of carbonyl groups plays an important role
in organic, medicinal, carbohydrate and drug design
chemistry, and multi-steps synthesis of many natural
products.1 For example, oxathioacetals were used as acyl
carbanion equivalents2 for carbon-carbon bond forming
reactions, and also serve as valuable starting materials for
the enantioselective synthesis of tertiary a-hydroxyl alde-
hydes, a-hydroxyl acids and glycols. There are many
methods for preparation of oxathioacetals and dithioace-
tals using protic acids or Lewis acids such as p-TsOH,3
Bi(NO3)3,4 BF3·OEt2,5 SO2,6 ZnCl2,7 ZrCl4,8 and TMS-
OTf.9 However, many of these methods require drastic
conditions, expensive reagents and longer reaction times,
and give low yields. Thus, there is continuing need to de-
velop milder and more efficient methods for synthesis of
oxathioacetals and dithioacetals. Recently, polymer or in-
organic solid-supported reagents have been widely used
in organic synthesis. Efficient methods for a conversion of
carbonyl compounds into oxathioacetals and dithioacetals
using silica gel-supported reagents such as SOCl2/SiO2,10
CoBr2/SiO2,11 ZrCl4/SiO2,12 TaCl5/SiO2,13 Cu(OTf)2/
R1
R2
O
S
HO
SH
O
15
SiO214 and AlCl3/SiO2 have been reported. However, it
PPA/SiO2
R1
R2
Dichloroethane
could not say that these methods were not necessarily
good methods in view of environmentally friendly ap-
proaches, e.g. in the preparation of SOCl2/SiO2, large
amounts of HCl and SO2 were released upon mixing thio-
nyl chloride and silica gel. Although the reagents such as
CoBr2/SiO2, ZrCl4/SiO2, TaCl5/SiO2 and Cu(OTf)2/SiO2
were effective reagents, these reagents could not be re-
used for subsequent reactions. AlCl3/SiO2 was a reusable
R1
R2
S
S
HS
SH
Scheme 1
For instance, a mixture of benzaldehyde (2.0 mmol), mer-
captoethanol (2.4 mmol) and PPA/SiO2 (0.5 g) in dichlo-
roethane (5 mL) was stirred at room temperature for 30
minutes, and then the used supported reagent was re-
moved by filtration. 2-Phenyl-1,3-oxathiolane was ob-
tained in 99% yield. As shown in Table 1, when SiO2 was
used instead of PPA/SiO2, the reaction did not proceed
SYNLETT 2004, No. 13, pp 2307–2310
Advanced online publication: 08.09.2004
DOI: 10.1055/s-2004-832812; Art ID: U18804ST
© Georg Thieme Verlag Stuttgart · New York
0
3
.1
1
.2
0
0
4

2308
T. Aoyama et al.
LETTER
under similar conditions. Although the reaction using It is due to low solubility of PPA in dichloroethane that
PPA as a catalyst gave the product in 86% yield, it is im- the reaction using PPA gave lower yield than that in the
possible to recover PPA from the reaction mixture and re- reaction using PPA/SiO2. PPA is not soluble in nonpolar
use it. On the other hand, PPA/SiO2 was easily recovered organic solvents such as toluene and hexane. To exclude
from the reaction mixture by simple filtration and reused the possible leaching of PPA in solution from PPA/SiO2,
for the subsequent reaction without loss of the amount of the model reaction was examined. The slurry of PPA/SiO2
the catalyst (recovery 95%).19 The yield of 2-phenyl-1,3- in dichloroethane was stirred for 1 hour, and a mixture of
oxathiolane in sixth use of the catalyst was almost the benzaldehyde and ethanedithiol was added to the filtrate
same as that in the first use.
after the PPA/SiO2 was filtered off, and was stirred for one
hour. The reaction did not proceed and no dithioacetal was
detected.
Table 1 Comparative Effectiveness of Acid Catalyst, and Re-
cycling of PPA/SiO2 for the Synthesis of 2-Phenyl-1,3-oxathiolane
The reaction of a series of carbonyl compounds with mer-
captoethanol or 1,2-ethanedithiol was carried out in the
presence of PPA/SiO2 at room temperature to afford the
corresponding oxathioacetals or dithioacetals in high
yields. The results obtained were shown in Table 2. Aro-
matic aldehydes were converted to the corresponding ox-
athioacetals and dithioacetals in excellent yields except
for the reactions of aromatic aldehydes having electron-
withdrawing groups with mercaptoethanol. Aldehydes
having electron-withdrawing groups were converted to
desired products in high yields when using two times
amounts of PPA/SiO2 in the reaction of aldehydes having
electron-donating groups (runs 5 and 6).
SH
O
HO
CHO
Catalyst
S
Catalyst
Yield (%)
None
0
0
SiO2
PPA
86
99
99
99
84
89
89
PPA/SiO2
PPA/SiO2 (1)a
PPA/SiO2 (2)a
PPA/SiO2 (3)a
PPA/SiO2 (4)a
PPA/SiO2 (5)a
The reactions of aliphatic aldehydes with 1,2-ethane-
dithiol also gave the expected products in high yields,
whereas the reactions with mercaptoethanol required a
greater amount of PPA/SiO2 to obtain the product in high
yield (run 10–13). Acyclic ketones were less reactive
than cyclic ketones. The reactivity of acyclic ketones de-
creased with increasing its steric hindrance. The reactivity
of 1,2-ethanedithiol against aldehydes was higher than
that of mercaptoethanol. In contrast, 1,2-ethanedithiol
was less reactive than mercaptoethanol against ketones.
a Parenthetic numbers indicate the number of reuses of PPA/SiO2.
Table 2 Preparation of Oxathioacetals and Dithioacetals
Run
1
Aldehydes (ketones)
Benzaldehyde
Alcohols
Molar ratio
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
PPA/SiO2 (g)
Time (h)
0.5
Yield (%)a
99
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
0.5
0.5
0.5
0.5
1.0
1.0
0.5
0.5
0.5
1.0
1.0
1.0
2
p-Methylbenzaldehyde
p-Methoxybenzaldehyde
p-Bromobenzaldehyde
p-Cyanobenzaldehyde
p-Nitrobenzaldehyde
1-Naphthaldehyde
2-Naphthaldehyde
Thiophene-2-aldehyde
Decanal
0.5
100
95
3
0.5
4
0.5
98
5
0.5
80
6
0.5
82
7
0.5
100
100
91
8
0.5
9
0.5
10
11
12
0.5
99
10-Undecenal
0.5
97
Phenylpropionaldehyde
0.5
63
Synlett 2004, No. 13, 2307–2310 © Thieme Stuttgart · New York

LETTER
Conversion of Carbonyl Compounds into Oxathioacetals and Dithioacetals
2309
Table 2 Preparation of Oxathioacetals and Dithioacetals (continued)
Run
13
Aldehydes (ketones)
Cyclohexanal
Alcohols
Molar ratio
1:1.2
PPA/SiO2 (g)
1.0
Time (h)
0.5
Yield (%)a
96
Mercaptoethanol
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
Cinnamaldehyde
Cyclohexanone
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
Mercaptoethanol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1,2-Ethanedithiol
1:1.2
1:1.2
1:1.2
1:1.5
1:1.5
1:1.5
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.5
1:1.5
1:1.5
0.5
0.5
0.5
1.0
1.0
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
1.0
1.0
0.5
0.5
0.5
0.75
2.0
2.0
0.5
0.5
0.5
0.5
0.5
0.5
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2.0
2.0
2.0
100
94
94
79
64
7b
Cyclopentanone
4-Heptanone
Phenylpropylketone
Benzophenone
Benzaldehyde
97
99
99
94
94
100
95
95
86
95
100
97
96
99
87
72
78
45
3b
p-Methylbenzaldehyde
p-Methoxybenzaldehyde
p-Bromobenzaldehyde
p-Cyanobenzaldehyde
p-Nitrobenzaldehyde
1-Naphthaldehyde
2-Naphthaldehyde
Thiophene-2-aldehyde
Decanal
10-Undecenal
Phenylpropionaldehyde
Cyclohexanal
Cinnamaldehyde
Cyclohexanone
Cyclopentanone
4-Heptanone
Phenylpropylketone
Benzophenone
a Isolated yield.
b Yield was determined by GLC.
In conclusion, we introduced a reusable and tractable acid References
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LETTER
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recovered by filtration from the reaction mixture, and then it
was put in the 50 mL round-bottom flask and dried in vacuo
at 100 °C for 2 h.
Synlett 2004, No. 13, 2307–2310 © Thieme Stuttgart · New York