Alumina perchloric acid (Al2O3-HClO4) as an efficient heterogeneous catalyst for modified preparation of trimethylsilyl ethers

Article abstract of DOI:10.1080/10426500802021539

A highly efficient and mild procedure for the trimethylsilylation of a wide variety of alcohols, including primary, benzylic, secondary, hindered secondary, tertiary, phenols, and oximes with hexamethyldisilazane (HMDS) using alumina perchloric acid (Al2O3-HClO4) as recyclable heterogeneous catalyst in excellent yields with short reaction times (3-65 min) under ambient conditions is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500802021539

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Alumina Perchloric Acid (Al
2
O -HClO ) as an Efficient
3
4
Heterogeneous Catalyst
for Modified Preparation of
Trimethylsilyl Ethers
Hamid Reza Shaterian a , Fahimeh Khorami a , Azita
Amirzadeh a & Majid Ghashang a
a Department of Chemistry, Faculty of Sciences ,
University of Sistan and Baluchestan , Zahedan, Iran
Published online: 10 Oct 2008.
To cite this article: Hamid Reza Shaterian , Fahimeh Khorami , Azita Amirzadeh &
Majid Ghashang (2008) Alumina Perchloric Acid (Al
O
-HClO ) as an Efficient
3 4
2
Heterogeneous Catalyst for Modified Preparation of Trimethylsilyl Ethers, Phosphorus,
Sulfur, and Silicon and the Related Elements, 183:11, 2865-2874
To link to this article: http://dx.doi.org/10.1080/10426500802021539
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Phosphorus, Sulfur, and Silicon, 183:2865–2874, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802021539
Alumina Perchloric Acid (Al2O3-HClO4) as an Efficient
Heterogeneous Catalyst for Modified Preparation of
Trimethylsilyl Ethers
Hamid Reza Shaterian, Fahimeh Khorami,
Azita Amirzadeh, and Majid Ghashang
Department of Chemistry, Faculty of Sciences, University of Sistan and
Baluchestan, Zahedan, Iran
A highly efficient and mild procedure for the trimethylsilylation of a wide variety
of alcohols, including primary, benzylic, secondary, hindered secondary, tertiary,
phenols, and oximes with hexamethyldisilazane (HMDS) using alumina perchloric
acid (Al O -HClO ) as recyclable heterogeneous catalyst in excellent yields with
2
3
4
short reaction times (3−65 min) under ambient conditions is described.
Keywords Alumina perchloric acid; heterogeneous catalyst; hexamethyldisilazane; hy-
droxyl groups; trimethylsilylation
INTRODUCTION
Trimethylsilylation of organic compounds having labile hydrogen atoms
is an important organic transformation. It is a frequently used protec-
tion method in multi-step sequence synthesis of natural products due
to the enhanced stability under a variety of conditions, solubility in
non-polar solvents, thermal stability, and the ease of removal which
is simply accomplished by acid or base induced hydrolysis giving only
unreactive siloxane as by-product. It is also used extensively for the hy-
droxyl compounds to increase their volatility for gas chromatography
and mass spectrometry.1,2
Several methods have been reported for this conversion, including
the reaction of an alcohol with trimethylsilylhalides in the presence
of a stoichiometric amount of a tertiary amine,3 with trimethylsilyl
Received 2 February 2008; accepted 29 February 2008.
We are thankful to the Sistan and Baluchestan University Research Council for partial
support of this work.
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
2865

2866
H. R. Shaterian et al.
triflate and trimethylsilylmethallylsulfinates, which are more reactive
than the chloride,4 allylsilanes in the presence of a catalytic amount
of p-toluenesulfonic acid4 iodine,5 trifluoromethanesulfonicacid6 and
Sc(OTf)3.7 Hexamethyldisilazane (HMDS) is frequently used for the
trimethylsilylation of hydroxyl groups. HMDS is an inexpensive and
commercially available reagent. Its handling does not require special
precautions, and the work-up is not time-consuming, because the by-
product of the reaction is ammonia, which is simple to remove from
the reaction medium. The low silylation power of HMDS is the main
drawback to its application. Therefore, there are variety of catalysts for
activating of this reagent, such as (CH3)3SiCl,8 K-10 montmorillionite,9
sulfonic acids,10 zirconium sulfophenyl phosphonate,11 ZnCl2,12 Enviro-
cat EPZGO,13 tungstophosphoric acid,14 iodine,15 lithium perchlorate,16
cupric sulfate pentahydrate,17 H–β Zeolite,18 MgBr2,19 lithium perchlo-
rate supported on silica gel,20 Al(HSO4)3,21 Al(OTF)3,22 magnesium
triflate,23 copper triflate,24 ZrCl4,25 silica-HClO4,26 and silica chloride.27
However, in most cases, a long reaction time, drastic reaction condi-
tions, or tedious work-up is needed. In addition, trimethylsilyl azide
is expensive and toxic. In continuation of our work28 on the applica-
tion of heterogeneous catalysts for the development of useful synthetic
methodologies, we now show that O-trimethylsilylated compounds can
be produced using Al2O3-HClO4 as an efficient, recyclable heteroge-
neous catalyst under ambient conditions (Scheme 1).
SCHEME 1
This catalyst is safe, easy to handle, environmentally benign,
presents fewer disposal problems and stable in reaction media. Al2O3-
HClO4 has been prepared from the reaction of neutral alumina with
perchloric acid.
RESULTS AND DISCUSSION
First, silylation of benzyl alcohols with HMDS in the presence of solid
Al2O3-HClO4 as a catalyst in various solvents and also under solvent-
free conditions at room temperature was investigated. The results were
summarized in Table I. In Table I, we show that acetonitrile as a solvent
is obviously the best choice for these reactions.

Alumina Perchloric Acid as an Efficient Heterogeneous Catalyst
2867
TABLE I Silylation of Benzyl Alcohols with HMDS in the Presence of
Solid Al2O3-HClO4(0.025 g) as Catalyst Under Solvent and
Solvent-Free Conditions at Room Temperature
Substrate/HMDS
Molar Ratio
Entry
Solventa
Time (min) GC Yield (%) Yield (%)b
1
2
3
4
5
6
Dichloromethane
Chloroform
Ethyl acetate
Hexane
Acetonitrile
Solvent-Free
1/0.8
1/0.8
1/0.8
1/0.8
1/0.8
1/0.8
60
30
40
130
9
135
100
100
100
100
100
100
89
91
87
93
93
89
aAmount of solvent = 2 ml; and bisolated yield.
To determine the optimum quantity of Al2O3-HClO4, the reaction of
benzyl alcohol (1 equiv) and HMDS (0.8 equiv) was carried out under
ambient conditions using different quantities of catalyst. The use of 50
mg of catalyst was resulted in the highest yield in 3 min (Table II).
Thus, we prepared a range of O-trimethylsilated compounds under the
optimized reaction conditions (Table III).
A wide range of structurally diverse and functionalized phenols, al-
cohols and oximes underwent silylation by this procedure to provide the
corresponding TMS ethers in good to excellent isolated yields (Table III,
Entries 1−24). Primary alcohols mostly reacted faster than secondary
and tertiary alcohols. Generally, in the all cases of benzyl, primary,
secondary, and tertiary alcohols, the reactions were completed within
less than 65 min in solvent-free conditions, accompanied by evolution
of NH3 gas from the reaction mixture. Inspection of the data in Table
III clearly shows that different types of hindered secondary, tertiary
alcohols and oximes were successfully converted to the corresponding
silyl ethers at ambient conditions (Table III). Amines (Table III, En-
tries 26−28), thiols (Table III, Entry 25) remained unaffected under
the reaction conditions.
TABLE II Optimization of the Amount of Catalyst in
the Synthesis of Benzyl Trimethylsilyl Ether
Entry
Al2O3-HClO4(g)
Time(min)
Yield (%)a
1
2
3
0.05
0.025
0.01
3
9
19
95
93
90
aIsolated yield.

2868
H. R. Shaterian et al.
TABLE III Silylation of Variety Hydroxyl Groups with HMDS in
the Presence of Solid Al2O3-HClO4 as Catalyst (0.05 g) Under
Ambient Conditions
Molar
ratio
substrate/ Time
Entry
1
Substrate
Product
HMDS
(min) Yield (%)a
1/0.8
3
3
(91-95)b
2
1/0.8
94
3
4
1/0.8
1/0.8
8
7
98
91
5
1/0.8
7
93
6
7
1/0.8
1/0.8
9
6
83
85
8
1/0.8
13
92
9
1/0.8
1/0.8
65
7
87
93
10
11
1/0.8
11
97
12
13
1/1.6
1/0.8
5
91
97
17
(Continued on next page)

Alumina Perchloric Acid as an Efficient Heterogeneous Catalyst
2869
TABLE III Silylation of Variety Hydroxyl Groups with HMDS in the
Presence of Solid Al2O3-HClO4 as Catalyst (0.05 g) Under Ambient
Conditions (Continued)
Molar
ratio
substrate/ Time
Entry
14
Substrate
Product
HMDS (min) Yield (%)a
1/0.8
1/0.8
4
9
96
95
15
16
1/0.8
6
96
17
18
1/0.8
1/0.8
4
4
95
96
19
1/0.8
4
93
20
21
1/0.8
1/1.6
3
4
94
96
(Continued on next page)

2870
H. R. Shaterian et al.
TABLE III Silylation of Variety Hydroxyl Groups with HMDS in the
Presence of Solid Al2O3-HClO4 as Catalyst (0.05 g) Under Ambient
Conditions (Continued)
Molar
ratio
substrate/
HMDS
Time
(min)
Entry
22
Substrate
Product
Yield (%)a
93
1/0.8
1/0.8
1/0.8
6
6
5
23
24
88
91
25
26
1/0.8
1/0.8
7
5
—
90
27
28
1/1.6
1/0.8
5
7
90
—
aThe pure isolated product(s) was characterized by comparison of their physical
data with those of known compounds.8−27 b Yields after five times using recovered of
the catalyst.

Alumina Perchloric Acid as an Efficient Heterogeneous Catalyst
2871
The suggested mechanism of the Al2O3-HClO4 catalyzed silylation
of hydroxyl groups is shown in Scheme 2. Al2O3-HClO4 can act as
Brønsted acid and also Lewis acid owing to the empty aluminum p or-
bital. Thus, in this mechanism, however operation process chart (OPC)
of catalyst in this works is unknown nonetheless according to the ob-
servations such as evolution of NH3in the reaction conditions, we have
suggested that an acid-base interaction in Al2O3-HClO4 as catalyst and
nitrogen in HMDS polarizes N-Si bond of HMDS to produce a reactive
silylating agent (I). A rapid reaction with alcohol then ensues, leading
to the ammonium silylating species (II) with concomitant release of the
corresponding silyl ether. Irreversible cleavage of (II) with alcohol led
to the fast evolution of ROTMS and also formation of the unstable com-
plexes of Al2O3-HClO4 with ammonia (III). Cleavage of this complex
with HMDS, led to the fast evolution of NH3. Release of Al2O3-HClO4
as catalyst from intermediate (III), re-enters catalytic cycle (Scheme 2).
SCHEME 2
The reusability of the catalysts is an important benefit and makes
them useful for commercial applications. Thus, the recovery and
reusability of Al2O3-HClO4 was investigated. The recyclability of the
catalyst in the reaction of benzyl alcohol and HMDS in the presence of
Al2O3-HClO4 was checked (Table III, Entry1). The separated catalyst
can be reused after washing with CH2Cl2 and drying at 100oC. The
catalyst was recovered in excellent yields and catalyst was used in the
mentioned reaction for five times; it showed the same activity such as
fresh catalyst without any loss of its activity.

2872
H. R. Shaterian et al.
In conclusion, a reliable, rapid, and environmentally benign method
for the preparation of trimethylsilyl ethers in a high to excellent yield
under ambient conditions has been developed, which involves the use of
recyclable Al2O3-HClO4as an inexpensive and non-hazardous solid acid
catalyst. In addition to the purity of the products, the short reaction
times and ease of work-up make the method advantageous. We are
currently exploring further applications of Al2O3-HClO4 for other types
of functional group transformations in our laboratories.
EXPERIMENTAL
All reagents were purchased from Merck and Aldrich and used without
further purification. 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.
Preparation of Al2O3-HClO4
We prepared Al2O3-HClO4 in a similar manner to that of the SiO2-
HClO4 procedure first reported by Chakraborti and Gulhane.29
HClO4 (1.045 g, 60% HClO4) was added to the suspension of neutral
alumina (Merck, 70−230 mesh, 11.85 g) in diethyl ether (75 mL). The
mixture was concentrated and the residue dried under vacuum at 100oC
for 72 h to afford Al2O3-HClO4 as a free flowing powder.
The amount of H+ in the Al2O3-HClO4 was determined by acid-base
titration according to the following reaction (Equation 1).
Al2O3 HClO4 −→ Al2O3 ClO4 + H3O
(1)
The librated H3O+ was titrated by standard NaOH and the amount of
H+ in Al2O3-HClO4 was calculated (1 g of Al2O3-HClO4 equal to 0.5
mmol H+).
General Procedure for Silylation of Alcohols Using HMDS
Catalyzed with Al2O3-HClO4
To a stirred solution of alcohol (10 mmol), HMDS (8 mmol) and acetoni-
trile (5 ml) as solvent was added Al2O3-HClO4 (0.5 g, 0.25 mmol) and
the mixture was stirred at room temperature for the time specified in

Alumina Perchloric Acid as an Efficient Heterogeneous Catalyst
2873
Table II. The reaction was followed by TLC (n-Hexane-EtOAc, 9:1). Af-
ter completion of the reaction, the heterogeneous catalyst was filtered,
silica-gel (2 g) was added to the solution and the solvent was evaporated
at reduced pressure. The resulting presorbed material was purified by
column chromatography using silica gel. Then, the pad of silica in the
column was washed with n-hexane (2 × 10 mL). Evaporation of the sol-
vent under reduced pressure gave pure product(s) (Table I). The desired
pure product(s) was characterized by comparison of their physical data
with those of known compounds.8–27
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