Trimethylsilylation of alcohols and phenols using KBr as an efficient and reusable catalyst

Article abstract of DOI:10.1080/00397910500501227

KBr acts as an efficient and reusable catalyst for the selective and efficient trimethylsilylation of benzylic, primary and secondary aliphatic alcohols and phenols with hexamethyldisilazane. All reactions were performed at room temperature under mild and

Full text of DOI:10.1080/00397910500501227

This article was downloaded by: [University of North Dakota]
On: 26 November 2014, At: 06:40
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Trimethylsilylation of Alcohols and Phenols
using KBr as an Efficient and Reusable
Catalyst
a
a
Farhad Shirini & Esmail Mollarazi
a
Department of Chemistry , College of Science, Guilan University , Rasht,
Iran
Published online: 16 Aug 2006.
To cite this article: Farhad Shirini & Esmail Mollarazi (2006) Trimethylsilylation of Alcohols and Phenols using
KBr as an Efficient and Reusable Catalyst, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:8, 1109-1115, DOI: 10.1080/00397910500501227
To link to this article: http://dx.doi.org/10.1080/00397910500501227
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

w
Synthetic Communications , 36: 1109–1115, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500501227
Trimethylsilylation of Alcohols and
Phenols using KBr as an Efficient and
Reusable Catalyst
Farhad Shirini and Esmail Mollarazi
Department of Chemistry, College of Science, Guilan University,
Rasht, Iran
Abstract: KBr acts as an efficient and reusable catalyst for the selective and efficient
trimethylsilylation of benzylic, primary and secondary aliphatic alcohols and phenols
with hexamethyldisilazane. All reactions were performed at room temperature under
mild and completely heterogeneous conditions in good to high yields.
Keywords: Alcohols, hexamethyldisilazane, KBr, phenols, trimethylsilylation
The hydroxy group is one of the versatile functional groups in organic
molecules, and its controlled manipulation is of great value in multistep
syntheses.
The conversion of hydroxy functional groups to their corresponding
trimethylsilyl ethers is a widely used method for protection of alcohols and
[
1,2]
phenols.
purpose,
Among the several reagents that have been used for this
hexamethyldisilazane (HMDS), as a cheap, stable, and commer-
[
3–5]
cially available reagent, has found a special position. Its handling does not
require special precautions, silylation using this reagent is nearly neutral,
and workup is not tim consuming. However, the low silylating power of
this reagent is the main drawback of its application, which needs forceful con-
[6]
ditions and long reaction times in many instances. To improve the silylating
power of HMDS, a variety of reagents have been reported; of them sulfonic
[7]
[8]
[9]
acid,
zirconium sulfophenyl phosphonate,
K-10 montmorilonite,
Received in the U.K. May 10, 2005
Address correspondence to Farhad Shirini, Department of Chemistry, College of
Science, Guilan University, Rasht 41335-1914, Iran. E-mail: shirini@guilan.ac.ir or
fshirini@yahoo.com
1
109

1
110
F. Shirini and E. Mollarazi
[
10]
[11]
Me SiCl
and silica chloride
provide an improvement, in most cases low selectivity, forceful conditions,
are examples. Although these procedures
3
[6,12]
and long reaction times have been observed.
In continuation of our ongoing effort to develop new methods for the
[13–15]
protection of the hydroxyl group,
herein we report a mild and efficient
method for trimethylsilylation of alcohols and phenols using hexamethyldisi-
lazane in the presence of KBr, as a neutral, reusable, and heterogeneous
catalyst (Scheme 1).
Different types of alcohols were subjected to trimethylsilylation using
this method at room temperature under completely heterogeneous reaction
conditions (Table 1). Trimethylsilylation of benzylic alcohols including acid
sensitive and electron-donating or withdrawing groups proceeded efficiently
with high isolated yields (Table 1, entries 1–14). Primary and secondary
aliphatic alcohols were also successfully converted to their corresponding
silyl ethers in almost quantitative yields at room temperature (Table 1,
entries 18–22). This method was found to be useful for trimethylsilylation
of diols and acyloins (Table 1, entries 15–17). No elimination and rearrange-
ment by-products were observed at all. Phenols also undergo silylation easily
using this method, and their corresponding silyl ethers can be isolated in good
to high yields (Table 1, entries 26–30). As shown in Table 1, tertiary alcohols
are resistant to this reagent system and remained intact in the reaction mixture
(
Table 1, entries 23–25). Therefore, this methodology shows selectivity and
is suitable for the selective trimethylsilylation of benzylic, primary and
secondary aliphatic alcohols and phenols in the presence of tertiary ones.
This is exemplified by the competitive reactions between 4-methoxybenzyl
alcohol and tert-butanol, between cyclohexanol and 1-adamantaol,
and between 4-phenyl phenol and triphenyl methanol (Table 1, entries
3
2–34). This method is not useful for silylation of allylic alcohols (Table 1,
entry 31).
We have found that KBr is a reusable catalyst, and even after five runs for
the silylation of alcohols and phenols with HMDS, the catalytic activity of
KBr was almost the same as that of the fresh catalyst.
The mechanism of the reaction is not clear, but the fast evolution of
NH3 gas from the reaction mixture and the reusability of the catalyst
directed us to accept the mechanism shown in Scheme 2 as a most
probable one. This mechanism shows that the first step of the reaction is
the probable production of the reactive intermediate 1, by the polarization
of the Si-N bond in HMDS by KBr. A rapid reaction with alcohol then
Scheme 1.

Trimethylsilylation of Alcohols and Phenols
1111
Table 1. Trimethysilylation of alcohols and phenols
Time Yield
a,b
(min) (%)
Entry
Substrate
Product
1
1
4
4
98
95
1
2
1
5
85
95
3
5
4
5
6
3
0
95
c
90
4
1
8
95
7
1
7
6
5
0
97
8
9
c
95
1
1
0
95
75
6
11
12
13
1
4
3
75
87
1
7
7
7
3
0
0
5
95
80
95
80
1
1
1
4
5
6
17
18
19
5
5
95
92
(
continued)

1
112
F. Shirini and E. Mollarazi
Table 1. Continued
Time Yield
a,b
(min) (%)
Entry
Substrate
Product
1
3
0
0
95
90
2
0
1
2
2
0
85
2
2
2
3
d
0
6
0
d
6
6
3
0
0
0
0
2
2
4
5
d
0
80
80
85
2
6
7
1
5
2
8
2
8
9
8
0
95
2
e
3
70
3
0
1
f
3
0
5
—
3
g
100
3
3
2
3
þ
g
0
100
g
1
0
þ
g
0
(
continued)

Trimethylsilylation of Alcohols and Phenols
1113
Table 1. Continued
Time Yield
a,b
(min) (%)
Entry
Substrate
Product
g
3
0
90
þ
34
g
0
a
Products were identified spectroscopically and also by the conversion of the silyl
ethers to their corresponding alcohols.
b
Isolated yields.
KBr 0.15 mmol is used.
c
d
Starting material was recovered unchanged.
HMDS 1.4 mmol is used.
Unidentified products.
e
f
g
GC yield.
ensues, leading to the unstable ammonia–KBr complex 2. Irreversible
cleavage of 2 leads to the fast evolution of NH3 and release of KBr,
which reenters to the catalytic cycle.
In conclusion, we have reported a mild and efficient method for the
preparation of silyl ethers using hexamethyldisilazane catalyzed by KBr.
The method offers several advantages including selectivity, short reaction
times, high yields of the products, cleaner reactions, and an inexpensive
reagent, which makes the reaction convenient and more economical.
Scheme 2.

1
114
F. Shirini and E. Mollarazi
EXPERIMENTAL
All of the products were characterized by comparison of their physical and
spectral data with those of known samples. All yields refer to isolated
products.
General Procedure for Trimethylsilylation of Alcohols and Phenols
HMDS (0.7 mmol) was added dropwise to a mixture of the substrate (1 mmol)
and KBr (0.1 mmol, 0.012 g) in CH CN (3 mL) for 2 min with stirring at room
3
temperature. The reaction was monitored by TLC. After completion of the
reaction, the solvent was evaporated under reduced pressure. n-Hexane
(5 mL) was added, and the catalyst was recovered by filtration and washed
with n-hexane (5 mL). The filtrate was washed with water (10 mL), and the
organic layer was dried over MgSO . Evaporation of the solvent under
4
reduced pressure afforded the silylated compounds in high purity. Further
purification proceeded by vacuum distillation or recrystallization to afford
the pure silyl ethers in good to high yields.
ACKNOWLEDGMENT
We are thankful to the Guilan University Research Council for partial support
of this work.
REFERENCES
1
2
3
4
5
6
. Greene, T. W.; Wutz, P. G.M. Protective Groups in Organic Synthesis, 3rd ed.;
Wiley: New York, 1991.
. Kocienski, P. J.; Enders, R.; Noyori, R.; Trost, B. M. ProtectiveGroups; Thieme:
Stuttgart, 1994.
. Morita, T.; Okamoto, Y.; Sakurai, H. Use of allylsilanes as a new type of silylating
agent for alcohols and carboxylic acids. Tetrahedron Lett. 1980, 21, 835.
. Murata, S.; Noyori, R. Silylation with a perfluorinated resinsulfonic acid trimethyl-
silyl ester. Tetrahedron Lett. 1980, 21, 767.
. Sinou, D.; Emziane, M. Trimethylsilylazide: A highly reactive silylating agent for
primary and secondary alcohols. Synthesis 1986, 1045.
. Bruynes, C. A.; Jurriens, T. K. Catalysts for silylations with 1,1,1,3,3,3-hexam-
ethyldisilazane. J. Org. Chem. 1982, 47, 3966.
7
8
. Goldschmidt, A. G.T. German Patent 2 758884.
. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.; Constantino, U. Hetero-
geneous catalysis in trimethylsilylation of alcohols and phenols by sulfophenyl
phophonate. Synth. Commun. 1999, 29, 541.
9
. Zhang, Z. H.; Li, T. S.; Yang, F.; Fu, C. G. Montmorillonite clay catalysis XI:
Protection and deprotection of hydroxyl group by formation and cleavage

Trimethylsilylation of Alcohols and Phenols
1115
of trimethylsilyl ethers catalyzed by motmorillonite K-10. Synth. Commun. 1998,
8, 3105.
0. Gauttret, P.; El-Ghamarti, S.; Legrand, A.; Coutrier, D.; Rigo, B. Synth. Commun.
996, 26, 707.
1. Shirini, F.; Zolfigol, M. A.; Mohammadi, K. A mild and efficient method for
chemoselective silylation of alcohols using hexamethyldisilazane in the presence
of silica chloride. Phosphorous, Sulfur Silicon Relat. Elem. 2003, 178, 1567.
2. Reference 8, Table, entry j.
2
1
1
1
1
1
3. Shirini, F.; Zolfigol, A. R.; Mohammadi, K. Acetyl-tethering silica as a novel
reagent for acetylation of alcohols under mild and heterogeneous conditions.
Bull. Korean Chem. Soc. 2003, 24, 519.
1
1
4. Shirini, F.; Zolfigol, A. R.; Mohammadi, K. Silica sulfuric acid as a mild and
efficient reagent for the acetylation of alcohols in solution and under solvent-
free conditions. Bull. Korean Chem. Soc. 2004, 25, 325.
5. Shirini, F.; Zolfigol, A. R.; Abedini, M. Al(HSO4)3 as a efficient catalyst for the
acetylation of alcohols in solution and under solvent-free conditions. Monatshefte
fur Chemie 2004, 135, 279.