Novel and highly efficient protection of aliphatic alcohols and phenols with hexamethyldisilazane in the presence of La(NO3) 3·6H2O

Article abstract of DOI:10.1080/10426500802509616

Aliphatic alcohols and phenols are protected with hexamethyldisilazane in the presence of lanthanum nitrate hexahydrate (La(NO₃) ₃·6H₂O) in excellent yields at room temperature. Taylor & Francis Group, LLC.

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Novel and Highly Efficient
Protection of Aliphatic
Alcohols and Phenols with
Hexamethyldisilazane in the
Presence of La(NO ) ·6 H O
3
3
2
a b
Batool Akhlaghinia
a
Department of Chemistry, Faculty of Sciences ,
Ferdowsi University of Mashhad , Mashhad, Iran
b
School of Chemistry , Damghan University of Basic
Sciences , Damghan, Iran
Published online: 21 Sep 2009.
To cite this article: Batool Akhlaghinia (2009) Novel and Highly Efficient Protection
of Aliphatic Alcohols and Phenols with Hexamethyldisilazane in the Presence of
La(NO ) ·6 H O, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:10,
3
3
2
2530-2535, DOI: 10.1080/10426500802509616
To link to this article: http://dx.doi.org/10.1080/10426500802509616
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Phosphorus, Sulfur, and Silicon, 184:2530–2535, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802509616
Novel and Highly Efficient Protection of Aliphatic
Alcohols and Phenols with Hexamethyldisilazane in the
Presence of La(NO ) ·6 H O
3
3
2
Batool Akhlaghinia
Department of Chemistry, Faculty of Sciences, Ferdowsi University
of Mashhad, Mashhad, Iran and School of Chemistry, Damghan
University of Basic Sciences, Damghan, Iran
Aliphatic alcohols and phenols are protected with hexamethyldisilazane in the
presence of lanthanum nitrate hexahydrate (La(NO3)3·6H2O) in excellent yields at
room temperature.
Keywords Alcohol; hexamethyldisilazane (HMDS); lanthanum nitrate hexahydrate;
phenol; trimethylsilyl ether
INTRODUCTION
The role of silyl groups has already been recognized as an impor-
tant part of organic chemistry from both analytical and synthetic
points of view, especially as a protecting group in many syntheses
1
of reasonable complexity. Generally the formation of silyl ethers is
achieved by treatment of the corresponding alcohols with silyl chlo-
2
3
rides or silyl triflates in the presence of a base, Li2S, and sometimes
4
a nonionic super base catalyst. However, some of these methods fre-
quently suffer from drawbacks such as the lack of reactivity or the
difficulty in removing the ammonium salts derived from the reaction
of the by-produced acid and the co-bases during the silylation reac-
tion. 1,1,1,3,3,3-Hexamethyldisilazane (HMDS) is a stable, commer-
cially available, and cheap reagent for trimethylsilylation of hydroxy
compounds, giving ammonia as the only byproduct. On the other hand,
Received 28 August 2008; accepted 24 September 2008.
We gratefully acknowledge the partial support of this study by Damghan University
Research Council.
Address correspondence to Batool Akhlaghinia, Department of Chemistry, Fac-
ulty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. E-mail: akhlagh-
inia@um.ac.ir or Department of Chemistry, Damghan University of Basic Sciences,
Damghan, Iran. E-mail: b akhlaghinia@dubs.ac.ir
2530

Protection of Alcohols with Hexamethyldisilazane
2531
because of easiness in handling and neutrality of this silylating reagent
using HMDS does not need special precautions. However, the low sily-
lating power of 1,1,1,3,3,3-hexamethyldisilazane is a main drawback
for its application, which needs forceful conditions and long reaction
5
times in many instances. A variety of catalysts such as (CH3)3SiCl,
6
7
ZnCl2, complexes of metal chlorides with nitrogen ligands, zirconium
sulfophenyl phosphonate, K-10 montmorillonite, and a special type
of catalyst with the general formula X -NH-X , in which at least one of
the groups X and X is electron-withdrawing such as an ester or amide
group, has also been reported to promote the silylation of a wide range
of functional groups using HMDS.1
8
9
1
2
1
2
0
Here we report the use of an efficient and cheap system for the
trimethylsilylation of aliphatic alcohols and phenols.
RESULTS AND DISCUSSION
Recently we have reported the trimethylsilylation of alcohols and phe-
4
+ 11
nols with HMDS in the presence of Cu(2,3-tmtppa)
, CuSO4· 5 H2O,
and anhydrous FeCl3.12 In continuation of this study we are especially
interested in exploring the potential use of a neutral catalyst. Here
1
3
according to the previous catalytic effect of La(NO3)3· 6 H2O, we
describe a new protocol for the mild and rapid trimethylsilylation of
a wide variety of aliphatic alcohols and phenols using HMDS and a
catalytic amount of La(NO3)3· 6 H2O. First, the protection of benzyl al-
cohol under the catalytic effect of La(NO3)3· 6 H2O was studied. Benzyl
trimethylsilyl ether was produced immediately in quantitative yield.
Employing a 1:1 ratio in acetonitrile at room temperature gave the best
results and produced the respective trimethylsilyl ethers in quantita-
tive yields (Table I). We then applied these conditions for the protection
of structurally different alcohols and phenols (Scheme 1).
As shown in Table I, this method is very suitable for the conversion
of primary, secondary, tertiary, and benzylic alcohols as well as aryl
alcohols to the corresponding trimethylsilyl ethers.
SCHEME 1

2532
B. Akhlaghinia
TABLE I Trimethylsilylation of Aliphatic Alcohols and Phenols Cat-
alyzed by La (NO
3
)
3
· 6H
2
O in Dry CH
3
CN
Substrate
Conversion%a
Isolated yield%
1
1
00
00
98
97
100
97
1
1
00
00
98
95
1
00
00
96
98
1
1
00
00
98
98
1
100
97
1
00
00
98
98
1
1
00
00
96
95
1
100
100
100
95
98
97
(Continued on next page)

Protection of Alcohols with Hexamethyldisilazane
2533
TABLE I Trimethylsilylation of Aliphatic Alcohols and Phenols Cat-
alyzed by La (NO
3
)
3
· 6H
2
O in Dry CH
3
CN (Continued)
Substrate
Conversion%a
Isolated yield%
97
100
85
80
1
00
90
73
8
0
90
85
8
0
5
78
90
9
90
88
85
60
70
80
58
67
50
46
aGC yield using n-octane as internal standard.
To estimate the selectivity of this new method, we studied the re-
action of some binary mixtures of substrates. Excellent selectivity was
observed in the conversion of primary alcohols to the corresponding
trimethylsilyl ethers in the presence of secondary and tertiary alcohols

2534
B. Akhlaghinia
TABLE II Selective Trimethylsilyl Ether Formation
from Different Binary Mixtures
Binary Mixture
Products
Yield (%)a
100
98
100
97
1
1
1
00
00
00
100
1
00
00
1
aGC yield using n-octane as internal standard.
(
Table II). Benzyl alcohol is selectively protected with this reagent in
the presence of phenol (Table II).
In this article, we have introduced La (NO3)3· 6 H2O as a novel,
efficient, and convenient solid acid catalyst for the trimethylsilylation
of hydroxyl groups. The new catalyst is reusable and is easily separated
from the reaction mixture. Workup and isolation of the product by this
protocol are also straight forward.

Protection of Alcohols with Hexamethyldisilazane
2535
EXPERIMENTAL
Chemicals were obtained from Merck and Fluka. FT-IR spectra were
1
recorded with a Perkin Elmer RXI spectrophotometer. H NMR spectra
were recorded with a Bruker Avance DPX 250 MHz instrument. The
products were purified by column chromatography and the purity of the
products was determined by GC on a Shimadzu GC 10-A instrument
using n-octane as internal standard or by thin layer chromatography
using silica gel polygram on SIL G/UV 254 plates.
General Procedure for Protection of Alcohols
To a flask containing La(NO3)3 · 6 H2O (0.004 g, 0.01 mmol) in dry ace-
tonitrile (3–5 mL), HMDS (0.576 g, 1 mmol) was added under stirring
at room temperature. Subsequently, the alcohol (1 mmol) was added.
GC analysis showed that the reaction was completed immediately. The
solvent was evaporated under reduced pressure. Column chromatogra-
phy of the crude product on silica gel using n-hexane as eluent gave the
corresponding trimethylsilyl ether in quantitative yield.
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