A mild, simple, efficient, and selective protection of hydroxyl groups using silica-supported sodium hydrogen sulfate as a heterogeneous catalyst

Article abstract of DOI:10.1080/10426500802066054

A mild, simple, novel, and highly efficient method for the rapid protection of various primary, secondary, tertiary aliphatic alcohols, aromatic alcohols, and oximes using hexamethyldisilazane (HMDS) in the presence of silica-supported sodium hydrogen sulfate (NaHSO4-SiO2), as an active, inexpensive, nontoxic, heterogeneous, and readily available catalyst under ambient conditions is described. Timethylsilyl ethers were prepared in high to excellent yields, with short reaction times under mild and almost neutral reaction conditions at room temperature. Copyright Taylor & Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon
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A Mild, Simple, Efficient,
and Selective Protection of
Hydroxyl Groups Using Silica-
Supported Sodium Hydrogen
Sulfate as a Heterogeneous
Catalyst
Hamid Reza Shaterian a , Razieh Doostmohammadi a
, Majid Ghashang a & Mashaallah Rahmani a
a Department of Chemistry, Faculty of Sciences,
University of Sistan and Baluchestan, Zahedan, Iran
Published online: 03 Nov 2008.
To cite this article: Hamid Reza Shaterian , Razieh Doostmohammadi , Majid
Ghashang & Mashaallah Rahmani (2008) A Mild, Simple, Efficient, and Selective
Protection of Hydroxyl Groups Using Silica-Supported Sodium Hydrogen Sulfate as a
Heterogeneous Catalyst, Phosphorus, Sulfur, and Silicon and the Related Elements,
183:12, 3127-3135
To link to this article: http://dx.doi.org/10.1080/10426500802066054
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Phosphorus, Sulfur, and Silicon, 183:3127–3135, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802066054
A Mild, Simple, Efficient, and Selective Protection
of Hydroxyl Groups Using Silica-Supported Sodium
Hydrogen Sulfate as a Heterogeneous Catalyst
Hamid Reza Shaterian, Razieh Doostmohammadi,
Majid Ghashang, and Mashaallah Rahmani
Department of Chemistry, Faculty of Sciences, University of Sistan and
Baluchestan, Zahedan, Iran
A mild, simple, novel, and highly efficient method for the rapid protection of various
primary, secondary, tertiary aliphatic alcohols, aromatic alcohols, and oximes using
hexamethyldisilazane (HMDS) in the presence of silica-supported sodium hydrogen
sulfate (NaHSO -SiO ), as an active, inexpensive, nontoxic, heterogeneous, and
4
2
readily available catalyst under ambient conditions is described. Timethylsilyl
ethers were prepared in high to excellent yields, with short reaction times under
mild and almost neutral reaction conditions at room temperature.
Keywords Alcohol; heterogeneous catalyst; hexamethyldisilazane; NaHSO4-SiO2;
oxime; silylation
INTRODUCTION
Organic synthesis involving less environmentally unfriendly processes
and under solvent-free conditions have been investigated worldwide
due to stringent environment and economic regulations.1 Toxic, ho-
mogeneous, corrosive liquid acid catalysts, such as H2SO4, HF, HBr,
HCl, CF3COOH, and complexes of BF3, are frequently used in or-
ganic synthesis.2 However, processes involving solid heterogonous cat-
alysts are inherently associated with problems such as high toxicity,
corrosive and polluting reagents, catalyst waste, difficulty in separa-
tion and recovery.2 Replacement of these conventional acids by solid
heterogeneous catalyst is desirable to achieve effective and catalyst
Received 16 January 2008; accepted 19 March 2008.
We are thankful to the Sistan and Baluchestan University Research Council for the
partial support of this research.
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
3127

3128
H. R. Shaterian et al.
handling, product purification and to decrease waste production. 3 Con-
sidering the facts that most of the organic reagents involved in fine
chemical synthesis are sensitive to harsh conditions, it is desirable
to choose catalysts, which can catalyze organic transformations under
mild conditions.3
The preparation of silyl ethers can be carried out by treatment of
alcohols with silyl chlorides or silyl triflates in the presence of an or-
ganic base.4−13 However, these methods have frequently suffered from
drawbacks such as lack of reactivity or the difficulty in removal of
amine salts.6 1,1,1,3,3,3-Hexamethyldisilazane (HMDS) is a stable,
commercially available, and inexpensive reagent for trimethylsilylation
of hydrogen-labile substrates, giving NH3 as the only by-product.4−6
Even though the handling of this reagent is easy, the low silylation
power of HMDS is the main drawback to its application; therefore,
there are a variety of catalysts for activating of this reagent, such as
(CH3)3SiCl,14 zirconium sulfophenyl phosphonate,15 ZnCl2,16 Envirocat
EPZGO,17 tungstophosphoric acid,18 K-10 Montmorillionite,19 iodine,20
22
lithium perchlorate,21 cupric sulfate pentahydrate,
H–β Zeolite,23
MgBr2,24 lithium perchlorate suported on silica gel,25 Al(HSO4)3,26
Al(OTF)3,27 magnesium triflate,28 copper triflate,29 silica sulfate,30 sil-
ica chloride,31 and SiO2-HClO4.32
However, in most of these cases, a long reaction time, drastic re-
action conditions, accompanied with side reactions, such as etherifi-
cation, oxidation, elimination, problem of corrosives, pollution or te-
dious work-up have been observed. In addition, many of these reagents
are moisture sensitive or expensive. The lack of a facile and effec-
tive synthetic methodology in many of these reports for the silylation
of hydroxyl groups prompted us to develop a convenient and practical
procedure for the protection of hydroxyl groups in the presence of silica-
supported sodium hydrogen sulfate as catalyst at room temperature.
In the present research for functional group transformation, we wish to
describe a new protocol for the mild and rapid trimethylsilylation of a
wide variety of hydroxyl groups using HMDS, and a catalytic amount of
silica-supported sodium hydrogen sulfate at room temperature. Silica-
supported sodium hydrogen sulfate is an active catalyst, inexpensive,
readily available, nontoxic, safe, easy to handle, environmentally be-
nign with fewer disposal problems (Scheme 1).
RESULTS AND DISCUSSION
To optimize the reaction conditions, initially, we converted benzyl alco-
hol (1mmol) to its corresponding benzylsilylether with the amount of

Protection of Hydroxyl Groups Using Sodium Hydrogen Sulfate
3129
SCHEME 1
silica-supported sodium hydrogen sulfate as catalyst and HMDS (0.7
mmol) in the presence of various solvents and also solvent-free condi-
tions at room temperature (Table I).
The results in Table I show that amongst these solvents, acetonitrile
was the solvent of choice in terms of time. Thus, we prepared a range of
silylethers under the optimized reaction conditions: hydroxyl compound
(1 eq), HMDS (0.7 eq), NaHSO4-SiO2 (0.28 eq), and acetonitrile (2 mL)
(Table II).
A wide range of various alcohols and oximes underwent silylation
by this procedure to provide the corresponding TMS ethers in good
to excellent isolated yields (Table II, Entries 1–16). Benzylic alcohols
and primary alcohols generally are protected faster than secondary
and tertiary alcohols. Trimethylsilylation of aldoxime and ketoxime
also produce the corresponding trimethylsilylated compounds at these
conditions (Table II, Entries 17–19), whereas thiophenol, 1,3-propane
ditiol (Table II, Entries 20, 21), aniline and phthalimide (Table II, En-
tries 22, 23) were intact under the reaction conditions. Generally, in
all cases, the reaction of benzyl, primary, secondary, tertiary alcohols,
and oximes were completed within less than 47 min, accompanied by
evolution of NH3 gas from the reaction mixture. Inspection of the data
in Table II clearly shows that different types of hindered secondary and
TABLE I Silylation of Benzyl Alcohols with HMDS in the
Presence of Solid NaHSO4-SiO2 as Catalyst Under Solvent
and Solvent-Free Condition at Room Temperature
Molar ratio
Substrate/HMDS/Catalyst
Time
(min)
GC Yield
(%)
Entry
Solventa
1
2
3
4
5
6
7
Dichloromethane
Chloroform
Ethyl acetate
n-Hexane
Solvent-Free
Diethyl ether
Acetonitrile
1/0.7/0.28
1/0.7/0.28
1/0.7/0.28
1/0.7/0.28
1/0.7/0.28
1/0.7/0.28
1/0.7/0.28
10
7
7
10
45
10
2
100
100
100
100
100
100
100
a The amount of solvent was chosen to 2 mL.

3130
H. R. Shaterian et al.
TABLE II Silylation of Alcohols and Oximes with HMDS in the
Presence of NaHSO4-SiO2 as Catalyst (0.28 mmol, 0.05 g) in
Acetonitrile Under Ambient Conditions
Entry
1
Product
Ratio Substrate/HMDS Time (min) Yield (%)a
1/0.7
1/0.7
1/0.7
2
2
4
93–97b
2
3
97
95
4
5
1/0.7
1/0.7
17
16
96
94
6
7
1/0.7
1/0.7
10
10
85
87
8
1/0.7
43
98
9
1/0.7
1/0.7
45
15
88
91
10
11
1/0.7
45
97
12
13
1/1.3
1/0.7
12
47
87
97
(Continued on next page)

Protection of Hydroxyl Groups Using Sodium Hydrogen Sulfate
3131
TABLE II Silylation of Alcohols and Oximes with HMDS in the
Presence of NaHSO4-SiO2 as Catalyst (0.28 mmol, 0.05 g) in
Acetonitrile Under Ambient Conditions (Continued)
Entry
14
Product
Ratio Substrate/HMDS Time (min) Yield (%)a
1/0.7
1/0.7
10
40
93
15
16
94
97
1/0.7
45
17
18
1/0.7
1/0.7
11
10
92
95
19
1/0.7
10
89
20
21
1/1.3
1/0.7
45
45
—
—
22
23
1/0.7
1/0.7
45
45
—
—
aYields refer to pure isolated products. All known products have been reported
previously in the literature and were characterized by comparison of IR and NMR
spectra with authentic samples.14−32b Yields after three time recovery of catalyst.

3132
H. R. Shaterian et al.
tertiary alcohols were successfully converted to the corresponding silyl
ethers under the same experimental conditions (Table II).
We also investigated selective silylation of different binary mixture
of alcohols (Table III). This method was shown to be highly selective
for primary alcohols such as benzyl alcohols and 1-octanol compare to
secondary and tertiary alcohols (Table III, Entries 1–5). The primary al-
cohols were completely converted to the corresponding silylether, while
the secondary alcohols were converted to the corresponding silylated
product with 1–17% yield. Excellent selectivity was also observed for
the conversion of primary and secondary alcohols in the presence of
tertiary alcohols such as adamantanol (Table III, Entries 4–6).
The proposed mechanism of the silica-supported sodium hydrogen
sulfate catalyzed silylation of hydroxyl groups is shown in Scheme 2.
SCHEME 2
The reusability of the catalysts is one of the most important benefits
and makes them useful for commercial applications. Thus, the recovery
and reusability of NaHSO4-SiO2 was investigated. The recyclability
amount of the catalyst in the reaction of benzyl alcohol and HMDS using
NaHSO4-SiO2 was checked (Table II, Entry 1). After the reaction was
complete, the catalyst was filtered out and can be reused after washing
with ethyl acetate and drying at 100◦C. The recovered catalyst was
obtained in excellent yield and it was used in the mentioned reaction for
three times. It showed the same activity such as fresh catalyst without
any loss of its activity and converted benzyl alcohol to the desired TMS
ether in excellent yields (93–97%).

Protection of Hydroxyl Groups Using Sodium Hydrogen Sulfate
3133
TABLE III Selective Silylation of Different Binary Mixture
of Alcohols
Molar Ratio
Sub 1/Sub 2
/HMDS/Catalyst
GC
Yield
(%)
Substrate→Product
Time
(min)
Entry
1
Binary mixture
100
1/1/0.7/0.28
1/1/0.7/0.28
10
1
100
2
3
10
17
100
1/1/0.7/0.28
10
13
100
4
1/1/0.7/0.28
10
2
100
5
6
1/1/0.7/0.28
1/1/0.7/0.28
10
10
4
100
6

3134
H. R. Shaterian et al.
EXPERIMENTAL
All reagents were purchased from Merck and Aldrich and used with-
out further purification. NaHSO4-SiO2 was prepared according to the
reported procedure.33 All yields refer to isolated products after purifica-
tion. Products were characterized by comparison with authentic sam-
ples and by spectroscopy data (IR,1H NMR spectra). The NMR spectra
were recorded on a Bruker Avance DPX 300 and 500 MHz instrument.
The spectra were measured in CDCl3 relative to TMS (0.00 ppm). GC
analysis was run with Shimadzu GC-14A. IR spectra were recorded
on a JASCO FT-IR 460plus spectrophotometer. TLC was performed on
Silica-gel polygram SIL G/UV 254 plates.
General Procedure for Trimethylsilylation of Hydroxyl
Compounds Using NaHSO4-SiO2 as Catalyst
To a stirred solution of alcohols or oximes (1 mmol), HMDS (0.7 mmol),
and acetonitrile as solvent (2 ml), NaHSO4-SiO2 (0.28 mmol, 0.05 g) was
added at room temperature and the mixture was stirred at appropriate
time (Table II). The reaction was followed by TLC (n-hexane–EtOAc,
9:1). After completion reaction, the catalyst was filtered and separated
catalyst was washing with ethyl acetate and drying at 100◦C. Silica gel
(2 g) was added to the filtrate solution and the solvent was evaporated
at reduced pressure. The resulting solid material was purified by a
short column chromatography using n-hexane (2 × 10 mL) as eluent.
Evaporation of the solvent under reduced pressure gave pure product(s)
in high to excellent yield (Table II).
The desired pure product(s) was characterized by comparison of their
physical data with those of known compounds.14−32
CONCLUSION
In conclusion, an efficient method for the protection of alcohol and
oximes using HMDS under mild and ambient conditions is described.
Simple work-up procedure, including filtering the mixture through a
short pad of silica gel column, followed by evaporation of the solvent
and reusability of catalyst, is another advantage of this method.
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