Trimethylsilylation of alcohols and phenols, and direct acetylation of silyl ethers catalyzed by Fe(ClO4)3.6H2O

Article abstract of DOI:10.1080/10426500802336606

In this article, a mild and efficient protocol for the trimethylsilylation of various aliphatic and benzylic alcohols and phenols with trimethylsilyl chloride using a catalytic amount of ferric perchlorate at room temperature and relatively short reaction times in good to excellent yields is reported. Direct acetylation of trimethylsilyl ethers catalyzed with Fe(ClO4)3.6H2O(0.02 mmol)/Fe(ClO4)3SiO2(0.2 g) using acetic anhydride at ambient temperature is also reported.

Full text of DOI:10.1080/10426500802336606

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Trimethylsilylation of Alcohols
and Phenols, and Direct
Acetylation of Silyl Ethers
Catalyzed by Fe(ClO4)3.6H2O
Hossein A. Oskooie a , Majid M. Heravi a , Maryam
H. Tehrani a , Farahnaz K. Behbahani a & Omid M.
Heravi a
a Department of Chemistry, School of Sciences,
Azzahra University, Vanak, Tehran, Iran
Published online: 22 Jun 2009.
To cite this article: Hossein A. Oskooie , Majid M. Heravi , Maryam H. Tehrani ,
Farahnaz K. Behbahani & Omid M. Heravi (2009): Trimethylsilylation of Alcohols
and Phenols, and Direct Acetylation of Silyl Ethers Catalyzed by Fe(ClO4)3.6H2O,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:7, 1729-1737
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Phosphorus, Sulfur, and Silicon, 184:1729–1737, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802336606
Trimethylsilylation of Alcohols and Phenols, and Direct
Acetylation of Silyl Ethers Catalyzed by Fe(ClO4)3.6H2O
Hossein A. Oskooie, Majid M. Heravi, Maryam H. Tehrani,
Farahnaz K. Behbahani, and Omid. M. Heravi
Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
In this article, a mild and efficient protocol for the trimethylsilylation of various
aliphatic and benzylic alcohols and phenols with trimethylsilyl chloride using a
catalytic amount of ferric perchlorate at room temperature and relatively short re-
action times in good to excellent yields is reported. Direct acetylation of trimethylsi-
lyl ethers catalyzed with Fe(ClO ) .6H O(0.02 mmol)/Fe(ClO ) SiO (0.2 g) using
4 3 4 3
2
2
acetic anhydride at ambient temperature is also reported.
Keywords Acetylation; alcohols; Fe(ClO4)3.6H2O; phenols; trimethylsilylation
INTRODUCTION
Lately, several transformations in organic synthesis have been cat-
alyzed using ferric perchlorate, such as protection of alcohols and de-
protection of tetrahydropyranyl ethers,1 acetylation of alcohols and
phenols,2 aromatization of Hantzsch 1,4-dihydropyridines,3 and syn-
thesis of 1,5-bezodiazepine derivatives.4 In addition, ferric perchlorate
has been utilized to catalyze the acetylation of THP ethers5 and the
conversion of oximes to aryl- and alkyl hydrazones.6
On the other hand, the protection of alcohol functions by trimethylsi-
lyl group has been frequently and widely used in organic synthesis7 and
even more often used in analytical chemistry to prepare silyl ethers as
volatile derivatives of alcohols and phenols.8
Several methods have been developed for this conversion, including
trimethylsilyl halides/tertiary amine9 allylsilanes/p-toluenesulfonic
acid,10 iodine,11 trifluoromethanesulfonic acid,12 Sc(OTf)3,13 zinc
Received 11 March 2008; accepted 1 July 2008.
The authors are thankful for partial financial assistance from Azzahra University
Research Council.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of
Sciences, Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
1729

1730
H. A. Oskooie et al.
chloride,14 trimethylsilyl azide,15 tungstophosphoric acid,16 and
lithium perchlorate dispread in silica gel.17
During the multistep synthesis of natural products, the efficiency of
the synthetic protocol employed often depends largely on the protection
and the deprotection of the functional groups involved. To this end,
protecting groups have played a crucial role during the synthesis of
complex natural products. Therefore, protection and deprotection of
alcohols play essential roles in synthetic strategies.18
There are several methods for the deprotection of silyl ethers,
such as HF–MeCN,19 KF–Crown ether,20 BF3·Et2O–CHCl3,21 NBS,22
CF3SO3SiMe3–CH2Cl2,23 NH4F–MeOH,24 SiF4–MeCN,25 aqueous
acid,26 tetrabutylammonium fluoride (TBAF),27 K2CO3,28 Lewis
acids,29 neutral alumina,30 K2S2O8,31 oxidative cleavage of trimethylsi-
lyl ethers to the corresponding carbonyl compounds,32 and the conver-
sion of alcohols into acetates.33 The methods for the direct conversion
of silyl ethers to acetate are limited, and even those suffer from serious
drawbacks. Therefore, the introduction of new and economic methods
using a catalytic amount of reagent for such functional group transfor-
mations is still in demand.
Due to the importance of the protection–deprotection protocol, the
advantages of one-pot reactions, and our continuous interest in cat-
alytic reactions,34 in this article, we wish to report that ferric perchlo-
rate, in a catalytic amount, can protect aliphatic and benzylic alcohols
and phenols to silyl ethers. It also converts silyl ethers directly to the
corresponding acetates in excellent yields in a one-pot reaction using
acetic anhydride at ambient temperature (Schemes 1 and 2).
Fe(ClO4)3
R-OSiMe3
ROH + SiMe3Cl
R=alkyl, aryl
CH2Cl2, r.t.
SCHEME 1 Trimethylsilylation of alcohols and phenols by Fe(ClO4)3.6H2O.
Ac O, r.t.
2
ROSiMe
3
ROAc
Fe(ClO ) Or
4 3
Fe(ClO ) /SiO
4 3
2
R=alkyl, aryl
SCHEME 2 Direct acetylation of silyl ethers by Fe(ClO4)3.6H2O.

Trimethylsilylation of Alcohols and Phenols
1731
RESULTS AND DISCUSSION
Many silylating agents, such as chlorotrimethylsilane, 3,4-hexamethy
ldisiloxane, N,O-bis(trimethylsilyl)acetamide, hexamethyldisilazane
(HMDS), and ethyl(trimethylsilyl) acetate, have been used for the intro-
duction of a trimethylsilyl group onto a variety of alcohols. Trimethylsi-
lyl chloride is a cheap and commercially available compound that can
be used for the preparation of trimethylsilyl ethers from hydroxy com-
pounds. Its handling does not require special precautions, and the
work-up is not time consuming, as the by-product of the reaction is hy-
drochloric acid, which is simple to remove from the reaction medium. At
first, we tried to work with benzyl alcohol as a reagent and trimethylsi-
lyl chloride as a silylating agent without a catalyst under solvent-free
conditions for a long period of time, which gave no product. When we
used 0.02 mmol of Fe(Clo4)3.6H2O as a catalyst under the same reaction
conditions, benzyl trimethylsilyl ether was obtained in 98% yields after
25 min.
To investigate the merit and generality of this procedure, a variety of
primary benzyl alcohols bearing electron-withdrawing groups (chloro,
nitro; Table I, entries 8 and 9) and electron-releasing groups(methoxy,
hydroxyl, methyl; Table I, entries 6 and 7) were used. In all cases, the
formation of substituted benzyl trimethyl silylethers in high yields and
short reaction times using alcohols with electron–releasing groups were
observed, while alcohols with electron-withdrawing groups produced
trimethylsilyl ethers with significantly longer reaction times(Table I,
entry 8) or did not give any product at all (Table I, entry 9). It is likely
that electron-withdrawing groups decrease the nucleophilicity of the
hydroxyl group.
In order to evaluate the steric effect on the formation of the silyl
ether, a reaction with methyl-1-phenyl ethanol was attempted. The re-
action carried out, and silyl ether was obtained without any by-product
such as alkene from the elimination reaction (Table I, entry 10). In ad-
dition, aliphatic aldehydes were used, and the results were obtained as
well as for benzylic alcohols (Table I, entries 1, 2, and 4). Finally, it was
interesting to attempt this procedure with other hydroxyl compounds
such as phenols. Unfortunately, phenols, and particularly phenols bear-
ing electron-withdrawing groups, did not react (Table I, entries 12–16).
Trimethylsilyl ether compounds were then used in direct acetylation
reaction with Fe(ClO4)3.6H2O and Fe(ClO4)3-SiO2. The reactions car-
ried out using trimethylsilyl ethers and acetic anhydride at ambient
temperature obtained products in high yields and short reaction times
(Table II). The results of using both Fe(ClO4)3.6H2O and Fe(ClO4)3-
SiO2 were the same. However it is better to use Fe(ClO4)3-SiO2 instead

1732
H. A. Oskooie et al.
TABLE I Protection of Alcohols and Phenols Catalyzed Using
Fe(ClO4)3 in the Presence of Trimethyl Silyl Chloride
Entry
Substrate
Time(min)
75
Product
Yield%
95
1
2
3
95
30
93
98
4
5
80
25
97
98
6
45
94
7
8
2
96
95
50
9
500
40
—
—
10
98
11
45
97

Trimethylsilylation of Alcohols and Phenols
1733
TABLE I Protection of Alcohols and Phenols Catalyzed Using
Fe(ClO4)3 in the Presence of Trimethyl Silyl Chloride
(Continued)
Entry
Substrate
Time(min)
180
Product
Yield%
12
—
—
60
13
14
200
180
15
60
64
16
17
250
60
-
20
of Fe(ClO4)3.6H2O. Fe(ClO4)3 .6H2O is a hygroscopic compound, and
this property limits its use in reactions and it also needs special pre-
caution. The reaction using Fe(ClO4)3-SiO2 as a catalyst has all the
heterogenous catalysis advantages.
CONCLUSION
In summary, Fe(ClO4)3.6H2O and Fe(ClO4)3–SiO2, are found as a mild,
efficient, and novel catalyst for the silylation of various hydroxy sub-
strates with trimethylsilyl chloride under mild and neutral conditions.
This procedure provides a novel, efficient, and general methodology for
the preparation of trimethylsilyl ether in high yields. It is notewor-
thy to mention that Fe(ClO4)3.6H2O is a high hygroscopic compound,
which is readily prepared by the reaction of ferric hydroxide and can be
stored for a long time in desiccators. It is neither toxic, expensive, nor
explosive, even when heated in solution. In addition, Fe(ClO4)3–SiO2

1734
H. A. Oskooie et al.
TABLE II Fe(ClO4)3.6H2O-Catalyzed Direct Conversion of Silyl
Ethers to Acetate
Time(min)/Yield%
Fe(ClO4)3.6H2O
(0.02 mmol)/Fe
Entry
Substrate
(ClO4)3 /SiO2(0.2 g)
Product
1
40/94//20/94
2
3
55/93//40/93
20/97//13/97
4
5
6
50/95//35/95
15/98//8/98
30/96//15/96
7
10/97//7/97

Trimethylsilylation of Alcohols and Phenols
1735
TABLE II Fe(ClO4)3.6H2O-Catalyzed Direct Conversion of
Silyl Ethers to Acetate (Continued)
Entry
Substrate
Time(min)/Yield%
20/98//10/98
Product
8
9
30/98//15/98
10/97//7/97
10
is cheap, stable, easy to handle, and nontoxic catalyst. When used,
the work-up procedure is very simple, consisting only of filtration and
removal of the solvent.
EXPERIMENTAL
Preparation of Trimethylsilyl Ethers Using Fe(ClO4)3.6H2O:
Typical Procedure
A mixture of benzyl alcohol (0.54 g, 5 mmol), Fe(ClO4)3.6H2O
(0.05 g, 0.1 mmol), trimethylsilyl chloride (0.815 g, 7.5 mmol), and
dichloromethane (5 mL) was stirred at an ambient temperature.
The progress of the reaction was monitored by TLC (eluent, n-
hexane:diethyl ether, 4:1). After the completion of the reaction, water
was added to the mixture to the mixture (15 mL) and extracted with
CH2Cl2 (2 × 20 mL). The organic phase was separated and evaporated
to dryness under reduced pressure to give the product (Table I).
Acetylation of Trimethylsilyl Ethers Using Fe(ClO4)3 as
Catalyst
The trimethyl silyl ethers were prepared according to the above
procedure.

1736
H. A. Oskooie et al.
General Procedure
In a 10 mL flask, trimethyl silyl ether (1 mmol), acetic anhydride (1.5
mmol), and Fe(ClO4)3 (0.02 g, 1 mol%) were added and stirred at room
temperature for the indicated times in Table II. After the completion
of the reaction (monitored by TLC, eluent, n-hexane:diethyl ether, 4:1),
dichloromethane (20 mL) was added and Fe(ClO4)3/SiO2 filtrated. The
filtrate was neutralized with sodium bicarbonate (10%). Then the or-
ganic layer was separated from the aqueous phase by separatory fun-
nel. The organic phase was dried over MgSO4. The solvent was evap-
orated under reduced pressure, and the pure product was obtained in
high yield (Table II).
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