SO3H-functionalized silica for acetalization of carbonyl compounds with methanol and tetrahydropyranylation of alcohols

Article abstract of DOI:10.1016/j.tetlet.2004.04.186

Sulfonic acid group-functionalized amorphous silica acts as a highly effective and reusable catalyst for acetalization of various carbonyl compounds with methanol and tetrahydropyranylation of alcohols.

Full text of DOI:10.1016/j.tetlet.2004.04.186

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5135–5138
SO3H-functionalized silica for acetalization of carbonyl compounds
with methanol and tetrahydropyranylation of alcohols
Ken-ichi Shimizu,a,* Eidai Hayashi,a Tsuyoshi Hatamachi,b Tatsuya Kodamab
and Yoshie Kitayamab
aGraduate School of Science and Technology, Niigata University, Ikarashi-2, Niigata 950-2181, Japan
bDepartment of Chemistry and Chemical Engineering, Faculty of Engineering, Niigata University, Ikarashi-2,
Niigata 950-2181, Japan
Received 7 April 2004; revised 22 April 2004; accepted 26 April 2004
Abstract—Sulfonic acid group-functionalized amorphous silica acts as a highly effective and reusable catalyst for acetalization of
various carbonyl compounds with methanol and tetrahydropyranylation of alcohols.
Ó 2004 Elsevier Ltd. All rights reserved.
Acetalization is one of the most useful protecting
methods for carbonyl compounds. Dimethylacetals are
popular protecting groups and are generally synthesized
using p-toluenesulfonic acid (PTSA), triflic acid, and
pyridinium salts.1 These homogeneous catalysts present
limitations due to the use of toxic and corrosive re-
agents, the tedious work-up procedure, and the necessity
of neutralization of the strong acid media producing
undesired wastes. Various heterogeneous catalysts
(clays,2 sulfonic resins,3 and zeolites4) have been em-
ployed for the dimethylacetal formation with trialkyl
orthoformate. However, very few solid catalysts (Ce-
exchanged clay5 and siliceous mesoporous silica6) can
catalyze the acetalization with methanol. Protection of
alcohols as tetrahydropyranyl (THP) ethers is also use-
ful in organic synthesis, and generally protic and Lewis
acids are used as homogeneous catalysts for this reac-
tion.1a;7 From the environmental and economical
standpoints, various solid catalysts such as clays,8 sul-
fonic resins,9 and zeolites10 were also reported. How-
ever, some of these procedures suffer due to a high
catalyst to substrate ratio, a long reaction time and
formation of side products.
Sulfonic acid-functionalized silica11 can be an alternative
to commercially available sulfonic resin, which suffer
from low surface area and thermal stability. Although
the catalytic applications of the resins for organic syn-
thesis have been well established12 relatively few exam-
ples were reported on the use of sulfonic acid
mesoporous silica for organic reactions.11 As a part of
an ongoing research on heterogeneous catalysis of the
functionalized silica for clean synthesis,13 we present
herein the sulfonic acid-functionalized amorphous silica
(SO3H–SiO2) as a highly effective and reusable catalyst
for acetalization of aldehydes and ketones with metha-
nol and tetrahydropyranylation of alcohols.
Solvents and reagents were obtained from commercial
sources and were used without further purification. SH-
functionalized amorphous silica was prepared by sol–gel
method. To the solution of ethanol (20 mL) with
deionized water (15 mL), 44.8 mmol of tetraethylortho-
silicate (Si(OEt)4) and 3.55 mmol of 3-mercapto-
propyltriethoxysilane were added, and the mixture was
stirred at reflux temperature for 2h. The wet gel was
filtered and washed with ethanol, followed by drying in
vacuo at 25 °C. The SH groups were converted into the
sulfonic acid groups by an oxidation in a mixture of
aqueous H2O2 (31%, 5 mL) and CH3CN (30 mL) for 6 h
at a reflux temperature. After filtration and washing
with water and ethanol, the sample was then acidified in
0.1 M H2SO4 solution for 1 h, followed by washing with
water until neutral pH, and by drying at 100 °C for 6 h.
N2 adsorption experiment confirmed a high surface area
Keywords: Acetalization; Tetrahydropyranylation; Catalysis; Meso-
porous silica; Sulfonic acid.
* Corresponding author at present address: Department of Applied
Chemistry, Graduate School of Engineering, Nagoya University,
Chikusa-ku, Nagoya 464-8603, Japan. Tel.: +81-52-789-3191; fax:
+81-52-789-3193; e-mail: kshimizu@apchem.nagoya-u.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.186

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K. Shimizu et al. / Tetrahedron Letters 45 (2004) 5135–5138
(632m 2/g) of the catalyst. Sulfur content of the sample,
obtained by conventional elemental analysis, was
0.97 mmol gꢀ1 (C/S ¼ 3.78). The number of Hþ site of
SO3H–SiO2 determined by acid-base titration11f was
0.83 0.05 meq gꢀ1. This value corresponds to about
86% of the sulfur content, indicating that most of the
sulfur species on the sample are in the form of the sul-
fonic acid groups. Amorphous silica (Cab-O-Sil,
200 m2 gꢀ1) was used for a comparison.
(0.5 mol %, 13 mg) at room temperature in air for 20 h, a
complete conversion of the aldehyde was attained. The
acetal could be isolated with 79% yield after a simple
filtration and washing of the catalyst with CH2Cl2, fol-
lowed by evaporation of the solvent. No measurable by-
1
products were observed by TLC, GC, and H NMR
analyses. A possible contribution of homogeneous
catalysis was excluded as the following experiment.
When the SO3H–SiO2 was removed at an early stage of
the reaction (t ¼ 30 min, 38% yield), the reaction did not
proceed further, confirming that the heterogeneous
catalysis of SO3H–SiO2. The amorphous silica did not
catalyze the acetalization of hydrocinnamaldehyde after
24 h. As summarized in Table 1, SO3H–SiO2 was
First, we show the acetalization of carbonyl compounds
with methanol. When a solution of hydrocinnamalde-
hyde (2.5 mmol) in methanol (5 mL) is treated in the
presence of
a
catalytic amount of SO3H–SiO2
Table 1. SO3H–SiO2 catalyzed acetalization of carbonyl compounds with methanola
O
MeO OMe
R1 R2
SO3H-SiO2
MeOH(5mL)
R1
R2
2.5 mmol
Entry
Substrate
Time (h)
Product
Conv. (%)b
Yield (%)c
1
6
100
91
(85)
90
O
MeO
OMe
2d
3e
60
6
H
H
92
O
MeO
OMe
H
4
5
10
3
96
97
93 (75)
91 (88)
H
H
H
OMe
OMe
O
H
H
O
MeO
MeO
OMe
H
6
7
20
10
100
99
97 (79)
H
O
O
OMe
H
94
H
OMe
OMe
8
20
3
9292
87
H
H
H
O
MeO
O
OMe
O
9
82
90
H
O
MeO
OMe
H
R = H
R = Cl
10
1
97
H
R
R
R
R
11
12
13
3, 3f , 3g
1
1291
90, 88f , 90g
93
90, 88f , 87g
87
OMe
OMe
R=H
R=Bu
O
t
91
a Substrate (2.5 mmol), methanol (5 mL), catalyst (0.5 mol %) at 25 °C.
b Conversions of carbonyl compounds determined by GC using n-dodecane (0.2mmol) as an internal standard.
c Yields determined by GC using internal standard method. Isolated yields are in parentheses.
d 1-Butanal (50 mmol), methanol (50 mL), catalyst (0.01 mol %) at 25 °C.
e 1-Butanal (50 mmol), methanol (50 mL), catalyst (0.01 mol %) at a reflux temperature.
f Second cycle.
g Third cycle.

K. Shimizu et al. / Tetrahedron Letters 45 (2004) 5135–5138
5137
Table 2. SO3H–SiO2 catalyzed tetrahydropyranylation of alcoholsa
applicable for the acetalization of a wide variety of
aldehydes and some ketones. Using a small amount of
the catalyst under mild and simple reaction conditions
(at room temperature in air), aromatic aldehydes, a
conjugated aldehyde, aliphatic aldehydes, and cyclic
ketones underwent smooth transformation to the cor-
responding acetal in good yield. A linear ketone, 2-oc-
tanone, did not react at all (result not shown). After the
first run for the acetalization of p-chlorobenzaldehyde,
reusability of the SO3H–SiO2 was tested. The catalyst
can be easily separated from the reaction mixture by a
simple centrifugation, followed by washing with CH2Cl2
and by drying in vacuo at 298 K. The recovered SO3H–
SiO2 catalyzed the reaction at least three times keeping
good yields without any reactivation-treatment. An
acid-sensitive 2-furancarboxaldehyde was converted to
the corresponding dimethylacetal with 82% yield. The
double bond in d-citroneral did not undergo isomeri-
zation during acetal formation. These results indicate
that the reaction conditions are mild and not sufficiently
acidic to cause side-reactions. It was reported that linear
aldehydes were less reactive with Ce-exchanged clay5
and siliceous mesoporous silica6 at room temperature,
resulting in low yields (below 34%). In contrast, SO3H–
SiO2 catalyzed the acetalization of aliphatic aldehydes,
including linear aldehydes, with good yields at room
temperature (entries 1,2,4,5,6, and 8). Another advan-
tage of SO3H–SiO2 is its high turnover numbers. Using a
very small amount of the catalyst (0.01 mol %), the
acetal yield for 1-butanal was 90% after 60 h, which
corresponds to turnover numbers of 9000. To the best of
our knowledge, this is the highest turnover numbers for
the heterogeneously catalyzed acetalization of carbonyl
compounds by methanol. At a reflux temperature,
1-butanal was converted to the acetal with 89% yield
after 6 h, corresponding to the turnover frequencies of
SO3H-SiO2
CH Cl
+
ROH
2
2
O
O
OR
2.5 mmol
3.0 mmol
Entry Substrate
Time (h) Yield (%)b
1 1-Hexanol
21-Hexanol
1
1282
1
93 (80)
c
3
2-Octanol
Cyclohexanol
91 (86)
92(88)
92(89)
4
0.5
0.5
1
5
p-Methyl benzyl alcohol
Allyl alcohol
6
95, 94d, 96e, 95f , 99g
7
Propargyl alcohol
d-Citronerol
1
(78)
(87)
(82)
(81)
8
3
9
10
2-Hydroxyethyl acrylate
Benzhydrol
1
6
a Alcohol (2.5 mmol), DHP (3 mmol), CH2Cl2 (5 mL), catalyst
(0.5 mol %) at 25 °C.
b Yields determined by GC using n-dodecane (0.5 mmol) as an internal
standard. Isolated yields are in parentheses.
c 1-Hexanol (125 mmol), DHP (150 mmol), catalyst (0.01 mol %) at
25 °C.
d Second cycle.
e Third cycle.
f Fourth cycle.
g Fifth cycle.
addition, SO3H–SiO2 can catalyze the deprotection of a
THP ether. By stirring a mixture of the THP ether of
1-hexanol (2mmol) in methanol (5 mL) with SO 3H–SiO2
(0.5 mol %) at room temperature for 2h, the THP ether
was completely converted into 1-hexanol with 91% yield.
In conclusion, the present communication demonstrates
that the sulfonic acid group-functionalized silica acts as
a highly effective and reusable catalyst for acetalization
of various carbonyl compounds with methanol and
tetrahydropyranylation of alcohols. These methods do
not require strict anhydrous condition, use of dehy-
drated reagents, nor catalyst pre-treatment. The high
turnover numbers and applicability of the catalyst cou-
pled with its environmentally friendly nature should
make these methods particularly attractive.
1483 hꢀ1
.
SO3H–SiO2 was also shown to be effective for the tetra-
hydropyranylation of various alcohols by 3,4-dihydro-
2H-pyran (DHP) at room temperature (Table 2). For
example, cyclohexanol was completely converted after
0.5 h by SO3H–SiO2 (0.5 mol %), and the THP ether was
isolated with 88% yield after a simple filtration and
washing of the catalyst with CH2Cl2, followed by an
evaporation. Note that the amorphous silica did not
catalyze the reaction. The filtrate after the reaction for
5 min showed no catalytic activity, confirming the het-
erogeneous catalysis of the SO3H–SiO2. As shown in
Table 2, primary, secondary, benzylic, allylic and acet-
ylenic alcohols were converted to the corresponding
THP ethers with good yields. The low acid strength of
the catalyst and mild reaction conditions have not
affected double or triple bonds during the reaction of
allylic and acetylenic alcohols. The double bond in
d-citronerol did not undergo isomerization during the
reaction. For the syntheses of THP ether from allyl
alcohol, SO3H–SiO2 was reused without any reactiva-
tion-treatment at least 4 times. The reaction of 1-hexa-
nol (125 mmol) and 3,4-dihydro-2H-pyran (150 mmol)
proceeded in the presence of only 0.01 mol % of SO3H–
SiO2 in the solvent-free condition, and 82% yield and
turnover numbers of 8200 were attained after 12 h. In
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