Vanadium hydrogen sulfate (I): Chemoselective trimethylsilylation of alcohols and deprotection of trimethylsilyl ethers

Article abstract of DOI:10.1002/jccs.200800140

Trimethylsilylation of alcohols with hexamethyldisilazane (HMDS) catalyzed by V(HSO₄)₃ under mild and completely heterogeneous reaction condition is reported. The method is highly chemoselective for the protection of alcohols in the presence of phenols, amines and thiols. Also, the deprotection of trimethylsilyl ethers is performed in the presence of V(HSO ₄)₃ at room temperature in good to high yields.

Full text of DOI:10.1002/jccs.200800140

Journal of the Chinese Chemical Society, 2008, 55, 943-946
943
Communication
Vanadium Hydrogen Sulfate (I): Chemoselective Trimethylsilylation of
Alcohols and Deprotection of Trimethylsilyl Ethers
a,
Farhad Shirini, * Mohammad Ali Zolfigol, Masoumeh Abedini and Ali Reza Sakhaei
b
a
a
a
Department of Chemistry, College of Science, University of Guilan, Rasht, zip 41335, I. R. Iran
b
College of Chemistry, Bu-Ali Sina University, Hamadan, Iran
4 3
Trimethylsilylation of alcohols with hexamethyldisilazane (HMDS) catalyzed by V(HSO ) under
mild and completely heterogeneous reaction condition is reported. The method is highly chemoselective
for the protection of alcohols in the presence of phenols, amines and thiols. Also, the deprotection of tri-
4 3
methylsilyl ethers is performed in the presence of V(HSO ) at room temperature in good to high yields.
Keywords: Trimethylsilylation; Vanadium hydrogen sulfate; Hexamethyldisilazane; Alcohols;
Deprotection.
INTRODUCTION
The hydroxyl group is present in a number of com-
Aldrich. Products were separated and purified by different
chromatographic techniques and were identified by the
comparison of their IR, NMR and refractive index with
those reported for the authentic samples. All yields refer to
the isolated products. The purity determination of the sub-
strate and reaction monitoring were accompanied by TLC
on silica-gel polygram SILG/UV 254 plates.
pounds of biological and synthetic interest. Protection and
deprotection of this functional group during a multi-step
synthesis is an important process which is under the con-
1
siderable attention of many organic chemists. Trimethyl-
silylation is one of the best candidates widely used for this
purpose. The transformation of alcohols to the correspond-
ing trimethylsilyl ethers is a very common way for the pro-
4 3
Preparation of V(HSO )
A 500 mL suction flask was equipped with a constant
pressure dropping funnel. A gas outlet was connected to a
vacuum system through an absorbing solution (water) and
an alkali trap. Anhydrous vanadium trichloride (78.7 g, 0.5
mol) was charged in to the flask and concentrated sulfuric
acid (147.1 g, 1.5 mol) was added dropwise over a period
of 10 min at room temperature. HCl gas was evolved imme-
2
-4
tection of the hydroxyl group.
One of the reported reagents for the silylation is hexa-
methyldisilazane (HMDS), which is a cheap and commer-
5
,6
cially available reagent. Its handling dose not need a spe-
cial precaution and the work-up is not time-consuming, as
the by-product of the reaction is ammonia, which is simple
to remove from the reaction medium.
2 4
diately. After completion of the addition of the H SO , the
However, the low silylating power of HMDS is a
main drawback for its application, which needs forceful
mixture was shaken for 20 min at 50 °C, meanwhile, the re-
sidual HCl was exhausted by suction. An olive drab solid
material was thus obtained (170.9 g).
7
conditions and long reaction times in many instances.
Avariety of catalysts have been used for the activation of
General procedure for trimethylsilylation of alcohols
8
-11
HMDS. Although, these methods are suitable for many
synthetic conditions, usually low selectivity, forceful con-
ditions, long reaction times and use of the expensive re-
agents have been observed in many of these reports.
4 3
To a mixture of the substrate (10 mmol) and V(HSO )
(0.3 mmol) in MeCN (30 mL), HMDS (10 mmol) was
added dropwise within 5 min under stirring at room tem-
perature. After completion of the reaction (TLC), the mix-
ture was filtered through a silica-gel pad and the filter cake
was washed with MeCN (2 ´ 10 mL). Evaporation of the
solvent gave the desired products in good to high yields.
EXPERIMENTAL
Chemicals were purchased from Fluka, Merck and
*
Corresponding author. Fax: +98-131-3220066; E-mail: shirini@guilan.ac.ir

9
44 J. Chin. Chem. Soc., Vol. 55, No. 5, 2008
Shirini et al.
a
Table 1. Trimethylsilylation of alcohols and deprotection of obtained products
Protection
Deprotection
Entry
Substrate
b
b
Time (min)/Yield (%)
Time (min)/Yield (%)
1
2
3
4
5
6
7
8
9
4-ClC H CH OH
2
5/95
5/92
10/90
5/92
6
4
2-ClC H CH OH
6
4
2
4-BrC H CH OH
6
5/90
10/95
10/87
10/90
1/95
4
2
2-BrC H CH OH
4
5/87
6
2
3,4-Cl C H CH OH
2
5/92
6
3
2
2-MeC H CH OH
4
1/92
6
2
4-Me CHC H CH OH
2
5/92
1/90
2
6
4
4-Me CC H CH OH
3
5/95
1/90
6
4
2
2-NO C H CH OH
2
30/90
20/87
10/90
5/92
10/92
1/90
6
4
2
1
0
3-NO C H CH OH
2 6 4 2
11
2-MeOC H CH OH
6
10/85
1/92
4
2
1
1
1
1
1
1
1
2
3
4
5
6
7
8
3-MeOC H CH OH
6 4 2
PhCH(OH)CH3
PhCH(OH)Ph
12/95
5/93
10/90
1/95
4-ClC H CH(OH)Ph
6
10/90
5/90
5/85
4
PhCH CH OH
2
1/90
2
PhCH CH CH OH
2
10/95
15/87
5/92
2
2
PhCH(CH )CH OH
2
10/90
3
CH OH
2
1
2
9
0
15/85
10/90
5/92
6/86
HO
OH
OH
2
2
1
2
20/92
20/90
7/85
10/90
2
2
2
a
3
4
5
4-MeC H NH
2
30/00
30/00
60/00
—
—
—
6
5
4-BrC H SH
6
5
2,4-Cl C H OH
6
2
3
Products were characterized by their physical constants, comparison with authentic samples
and IR and NMR spectroscopy.
b
Yields are based on isolated products.
General procedure for deprotection of trimethylsilyl
ethers
RESULTS AND DISCUSSION
In recent years, we were interested to develop the ap-
1
2-14
A mixture of trimethylsilyl ethers (10 mmol) and
plication of hydrogen sulfate salts in organic chemistry.
In continuation of these studies, here in we wish to report
the preparation of V(HSO , as a new and efficient hydro-
4 3
V(HSO ) (0.3 mmol) in methanol (50 mL) was stirred at
room temperature for the appropriate time (Table 1). After
completion of the reaction (TLC), the solvent was evapo-
4 3
)
gen sulfate salt, and its applicability in the promotion of the
trimethylsilylation of alcohols with HMDS. All reactions
2 2
rated, CH Cl (10 mL) was added and the mixture was fil-
tered through a short silica column. Evaporation of the sol-
vent gave the desired products in 90-95% yields.
were performed in CH
3
CN at room temperature producing
the desired products in excellent yields (Scheme I).

Vanadium Hydrogen Sulfate (I)
J. Chin. Chem. Soc., Vol. 55, No. 5, 2008 945
Table 2. Selective trimethylsilylation of alcohols
Entry
SubstrateO
Product binary mixture
4-ClC H CH OTMS
Time (min) Conversion (%)
100
4
-ClC H CH OH
6
4
2
6
4
2
1
+
,4-Cl C H OH
+
15
+
0
2
2,4-Cl C H OTMS
2 6 3
2
6
3
2
2
-ClC H CH OH
2
2-ClC H CH OTMS
4
100
+
6
4
6
2
2
3
+
-MeC H NH
+
10
4
4-MeC H NHTMS
6 4
6
4
2
0
-ClC H CH OH
2
2-ClC H CH OTMS
4
100
+
6
4
6
2
+
-BrC H SH
+
4-BrC H STMS
2
0
4
0
6
4
6
4
Table 3. Comparison of some of the results obtained by our
Scheme I
method (1), with some of those reported by Al(HSO )
4
3
1
2b
13
V(HSO ) , MeCN, r.t.
4
3
(2), Fe(HSO ) (3) and sulfonic acid-functionalized
4 3
10
ROH + HMDS
ROTMS
silica (4)
Substrate
V(HSO ) , MeOH, r.t.
4
3
Time (min)/Yield (%)
(2) (3)
05/87 090/85 120/60
Entry
(
1)
(4)
—
Yields and reaction times are given in Table 1. Bnzylic
1
2
3
2
-BrC H CH OH
6
4
2
alcohols, including different substituents such as Cl, Br,
2-NO
C
6
H
4
CH
2
OH 30/90 240/78 30/85 360/90
05/93 50/75 60/98
2
NO
methylsilyl ethers in good to high yields (Table 1, entries
-14). This method is also very useful for the silylation of
primary, secondary and tertiary aliphatic alcohols (Table
, entries 15-21). Phenols, amines and thiols are so stable
2
and OMe are converted to their corresponding tri-
PhCH(OH)Ph
—
1
are mild, heterogeneous reaction conditions, short reaction
times, high yields of the products, selectivity and easy
work-up.
1
under the same reaction conditions, that the starting mate-
rial was recovered unchanged after 1 h (Table 1, entries
2
2-24).
The selectivity of a method determines its broad of
ACKNOWLEDGEMENT
We are thankful to the University of Guilan Research
Council for the partial support of this work.
application in organic reactions. Because of this and on the
basis of the obtained results, we investigated the selective
silylation of benzylic and aliphatic alcohols, in the pres-
ence of phenols, amines and thiols. The obtained results are
reported in Table 2.
Received May 7, 2008.
REFERENCES
In order to show the efficiency of this method, Table 3
1
. (a) Reese, C. B. In Protective Groups in Organic Chemistry;
McOmie, J. F.; Ed.; Plenum Press: London, 1973. (b) Fieser,
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& Sons Inc.: New York, 1999.
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1
for relevant reagents in the literature.
0,12,13
Our investigation clarified that the deprotection of
2
3
4
. Aizpurua, J. M.; Palomo, C. Bull. Soc. Chim. Fr. Mem. 1982,
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2
65.
4 3 3
presence of V(HSO ) in CH OH (Table 1). The reaction is
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silylation of alcohols in the presence of phenols, amines
and thiols. The significant advantages of this methodology
1
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