Silica sulfuric acid as a reusable catalyst for efficient and simple silylation of hydroxyl groups using hexamethyldisilazane (HMDS)

Article abstract of DOI:10.1080/10426500701289781

At room temperature, alcohols and phenols are efficiently protected with hexamethyldisilazane (HMDS) in the presence of silica sulfuric acid in good to excellent yields. The catalyst can be recycled for subsequent reactions without any appreciable loss of efficiency. Copyright Taylor and Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon
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Silica Sulfuric Acid as a
Reusable Catalyst for Efficient
and Simple Silylation of
Hydroxyl Groups Using
Hexamethyldisilazane (HMDS)
Hossein Ghafuri a , Bagher Eftekhari-Sis a &
Mohammed M. Hashemi a
a Department of Chemistry, Sharif University of
Technology, Tehran, Iran
Published online: 07 Jun 2007.
To cite this article: Hossein Ghafuri , Bagher Eftekhari-Sis & Mohammed M. Hashemi
(2007) Silica Sulfuric Acid as a Reusable Catalyst for Efficient and Simple Silylation of
Hydroxyl Groups Using Hexamethyldisilazane (HMDS), Phosphorus, Sulfur, and Silicon
and the Related Elements, 182:7, 1645-1651, DOI: 10.1080/10426500701289781
To link to this article: http://dx.doi.org/10.1080/10426500701289781
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Phosphorus, Sulfur, and Silicon, 182:1645–1651, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701289781
Silica Sulfuric Acid as a Reusable Catalyst for Efficient
and Simple Silylation of Hydroxyl Groups Using
Hexamethyldisilazane (HMDS)
Hossein Ghafuri
Bagher Eftekhari-Sis
Mohammed M. Hashemi
Department of Chemistry, Sharif University of Technology, Tehran, Iran
At room temperature, alcohols and phenols are efficiently protected with hexam-
ethyldisilazane (HMDS) in the presence of silica sulfuric acid in good to excellent
yields. The catalyst can be recycled for subsequent reactions without any appreciable
loss of efficiency.
Keywords Hexamethyldisilazane; hydroxyl group; protection; silica sulfuric acid;
silylation
INTRODUCTION
Protection of the hydroxyl functional group is an important process in
multi-step synthesis. One of the popular methods for this purpose is
to convert hydroxyl group to their corresponding silylethers. Several
silylating agents such as chlorotrimethylsilane, hexamethyldisilazane
(HMDS) and N,O-bis (trimethylsilyl) acetamide, and so on. have
been developed and become available on the commercial scale.1,2 For
trimethylsilyl ethers, the most common preparative method is the
chlorotrimethylsilane/pyridine system. However, it is accompanied
by the formation of voluminous pyridine salts as a by-product and
requires a careful filtration of the salt before isolating the silylated
compounds. The product yields are not so high in most cases. HMDS
is a stable, cheap, commercially available compound that can be used
for the preparation of trimethylsilylethers from hydroxyl compounds,
giving ammonia as the only by-product. Even though the handling of
this reagent is easy, its main draw-back is its poor silylating ability;
Received November 20, 2006; accepted December 26, 2006.
Address correspondence to Mohammed M. Hashemi, Department of Chemist-
sry, Sharif University of Technology, P.O. Box 11365-9516, Tehran, Iran. E-mail:
mhashemi@sharif.edu
1645

1646
H. Ghafuri et al.
forceful conditions and long reaction times are required.3 Various
catalysts have been reported for the activation of HMDS in silylation
reactions.4−16 However, in most cases a long reaction time, drastic
reaction conditions, or tedious work-up is needed. In addition, many
of these reagents are moisture sensitive or expensive. The lack of a
facial and general synthetic methodology for the silylation of hydroxyl
groups prompted us to develop an efficient, convenient, and practical
procedure for the protection of hydroxyl groups under solvent-free
conditions and at room temperature.
Recently, silica sulfuric acid has emerged as a powerful solid acidic
catalyst in synthetic methodology.17−24 Silica sulfuric acid could eas-
ily be prepared by the reaction of silica gel and chlorosulfonic acid
(Scheme 1).25
SCHEME 1
As part of our research on chemical transformations,26−31 in this
article we report a simple and environmentally benign methodology for
the silylation of hydroxyl groups under solvent-free conditions and at
room temperature using silica sulfuric acid as the catalyst.
RESULTS AND DISCUSSION
Various alcohols and phenols were subjected to silylation with HMDS
using silica sulfuric acid as catalyst at room temperature under solvent-
free conditions. The overall reaction is shown in Scheme 2.
SCHEME 2
We started to study the trimethylsilylation catalyzed by silica sulfu-
ric acid by examining the conditions required for the reaction involving
2-chlorobenzyl alcohol (3 mmol) and HMDS (2.5 mmol) to give the cor-
responding silylether. The results are summarized in Table I. Entries
1–7 show the effect of various solvents on the time of the reaction and
yield of the product. Although acetonitrile, dichloromethane, acetone,
and solvent-free conditions afforded the product in high yields, we chose
solvent-free conditions for economical and environmental acceptability.

Silica Sulfuric Acid Catalyst for Silylation
1647
TABLE I Reaction of 2-Chlorobenzyl Alcohol (3 mmol) and
HMDS (0.25 mmol) under Different Conditions
Entry
Solvent
Catalyst amount (g)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
THF
CH2Cl2
Acetone
CH3CN
0.25
0.25
0.25
0.25
0.25
0.25
0.20
0.12
0
2
2
2
2
2
5
5
5
80
86
92
90
94
EtOAc
90
Solvent-free
Solvent-free
Solvent-free
Solvent-free
92, 88, 80a
75
60
10
aRecovered catalyst was used for three times.
Entry 6 describes the yields of three consecutive reactions leading to 2-
chlorobenzyl trimethylsilyl ether. In these experiments the product was
isolated by filtration, the solid residues washed with dichloromethane,
and the remaining catalyst reloaded with fresh reagents for further
runs. No significant decrease in the yield was observed demonstrating
that silica sulfuric acid can be reused as a catalyst in trimethylsilylation
of alcohols and phenols. The optimum amount of catalyst (0.25 g) was
determined from experiments corresponding to entries 6–8. Entry 9
shows the effect of silica sulfuric acid in the reaction. The best reaction
conditions require the presence of small amounts of silica sulfuric acid
(0.25 g) and 2.5 mmol of HMDS with respect to the alcohols (3 mmol)
at room temperature under solvent-free conditions (Entry 6).
In order to understand the scope and limitations of this silica sul-
furic acid catalyzed procedure for the protection of hydroxyl groups,
various phenols and alcohols were treated with HMDS under solvent-
free conditions. The results are shown in Table II and Table III. Primary,
secondary, allylic and benzylic, sterically hindered, and acid-sensitive
alcohols, as well as phenols can be converted to the corresponding
trimethylsilyl ethers under these conditions. The reactions are very
fast; even with bulky and acid-sensitive alcohols to give high yields in
few minutes at room temperature.
In conclusion, SiO2 SO3H is found to be an efficient and simple cata-
lyst for the silylation of various hydroxyl substrates with HMDS under
very mild conditions. The present procedure provides a novel, efficient
and general methodology for the preparation of trimethylsilylethers in
high yields. In addition, SiO2-SO3H is cheap, stable, easy to handle and
nontoxic. The work-up process is very simple, consisting of merely fil-
tration and removal of solvent. Furthermore, SiO2 SO3H can be reused

1648
H. Ghafuri et al.
TABLE II Silylation of Various Phenols with HMDS
Entry
1
Phenol
Time (min)
5
Yield (%)a
86
2
3
4
5
5
5
5
5
92
89
90
94
6
7
5
5
90
94
8
5
5
90
93
9
10
100
45b
aAll yields refer to isolated products characterized by spectroscopic
data (IR and NMR); and bWhen the reaction was carried out in
CH2Cl2 the product was obtained in 80% yield within 15 min.
several times. After the reaction is complete, CH2Cl2 or petroleum ether
is added under stirring, and SiO2 SO3H is precipitated and separated
by filtration. This simple work up also allows facile recovery of the re-
action products.

Silica Sulfuric Acid Catalyst for Silylation
1649
TABLE III Silylation of Various Alcohols with HMDS
Entry
1
Alcohol
Time (min)
10
Yield (%)a
76
2
3
15
10
82
85
4
5
15
15
53
89
6
10
75
7
8
5
10
90
93
9
10
11
12
13
5
7
5
5
5
92
85
93
92
90
aAll yields refer to isolated products characterized by spectroscopic
data (IR and NMR).
EXPERIMENTAL
NMR spectra were recorded on a Bruker ACF 500. IR spectra were mea-
sured using a Perkin Elmer 781 spectrometer. Column chromatography
was performed on silica gel, Merck grade 60. CH2Cl2 was distilled be-
fore use. Chemicals were purchased from Fluka or Merck. All of the
products are known and were identified by comparison of their spec-
tral data with those of authentic samples. The progress of reaction was
monitored by thin-layer chromatography (TLC) on silica gel.

1650
H. Ghafuri et al.
General Procedure for the Preparation of Trimethylsilylethers
of Alcohols and Phenols Using HMDS Catalyzed with Silica
Sulfuric Acid
To a mixture of alcohols or phenols (3 mmol) and 0.25 g of SiO2-SO3H,
HMDS (2.5 mmol) was added and stirred at room temperature for
the specified time (Tables II and III). When the reaction was com-
plete as monitored by TLC, CH2Cl2 or petroleum ether were added,
and SiO2-SO3H was removed by filtration. The solvent was evaporated
and silylether was isolated as an almost pure product. Further purifica-
tion was carried out by short-column chromatography on silica gel using
ethyl acetate/petroleum ether as the eluent, if necessary. All compounds
are known and were characterized on the basis of their spectroscopic
data (IR, NMR) and by comparison with those reported in the literature.
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