Fe(HSO4)3 promoted trimethylsilylation of alcohols and phenols in solution and under solvent-free conditions

Article abstract of DOI:10.1007/s00706-007-0695-1

Alcohols and phenols are efficiently converted to their corresponding trimethylsilyl ethers with hexamethyldisilazane (HMDS) in the presence of Fe(HSO₄)₃ in solution and under solvent-free conditions.

Full text of DOI:10.1007/s00706-007-0695-1

Monatshefte fu¨r Chemie 139, 17–20 (2008)
DOI 10.1007/s00706-007-0695-1
Printed in The Netherlands
Fe(HSO4)3 Promoted Trimethylsilylation of Alcohols and Phenols
in Solution and Under Solvent-Free Conditions
Farhad Shirini1;ꢀ, Mohammad A. Zolfigol2, and Abdol-Reza Abri1
1
Department of Chemistry, College of Science, Guilan University, Rasht, I.R. Iran
2
College of Chemistry, Bu-Ali Sina University, Hamadan, I.R. Iran
Received March 29, 2007; accepted April 15, 2007; published online July 23, 2007
# Springer-Verlag 2007
Summary. Alcohols and phenols are efficiently converted to
plexes of metal chlorides [11], K-10 montmorillonite
their corresponding trimethylsilyl ethers with hexamethyldisi-
lazane (HMDS) in the presence of Fe(HSO4)3 in solution and
under solvent-free conditions.
[12], chlorotrimethylsilane [13], LiClO4 [14],
N,N0,N00,N000-tetramethyltetra-2,3-pyridinoporphyrazi-
nato copper(II) [15], and ZrCl4 [16]. Although these
procedures provide an improvement, in most cases
long reaction times, drastic reaction conditions, or
tedious work-up is needed. In addition, some of the
reagents are expensive and toxic or have to be pre-
pared in a time-consuming procedure.
Keywords. Alcohols; Fe(HSO4)3; Phenols; Trimethylsilyla-
tion; Solvent-free conditions.
Introduction
Trimethylsilylation is largely used to protect alco-
hols and phenols especially in the chemistry of ste-
roids, sugars, and natural product synthesis, and a
number of procedures are available for this purpose
[1–6]. The use of some silylating agents is limited
by their unavailability, toxicity, or the laborious pro-
cesses of purifying the products. Hexamethyldisil-
azane (HMDS) [7, 8], a cheap and commercially
available reagent, is one of the most widely used re-
agents for silylation of hydroxyl groups. 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 re-
move from the reaction medium. However, the low
silylating power of HMDS is the main drawback
to its application. Therefore, a variety of reagents
have been reported to improve the silylating power
of HMDS, as e.g., zirconium sulfophenyl phos-
phonate [9], sulfonic acids [10], nitrogen ligand com-
Results and Discussion
In our development of new methods for functional
group transformation, we are interested in the pro-
tection of hydroxyl groups as trimethylsilyl ethers.
Along these lines, we have introduced silica chloride
[17] and Al(HSO4)3 [18] as new reagents for the
promotion of silylation of hydroxyl groups with
HMDS. Even though the activity of HMDS has been
increased drastically in the presence of these re-
agents, this method suffers from limitations. In the
presence of silica chloride, the reaction can not be
performed under solvent-free conditions [19] and the
protection of phenols needs longer reaction times
[17]. On the other hand, HMDS is not able to protect
phenols in the presence of Al(HSO4)3 [20].
In view of this, we decided to overcome these
limitations by conducting the silylation reactions in
the presence of Fe(HSO4)3 [21]. Herein, we report
that Fe(HSO4)3 efficiently catalyzes the silylation of
ꢀ
fshirini@yahoo.com
Corresponding author. E-mail: shirini@guilan.ac.ir or

18
F. Shirini et al.
alcohols and phenols in solution and under solvent-
free conditions (Table 1, Scheme 1).
Trimethylsilylation of different types of alcohols
(including benzylic and primary, secondary, and ter-
Scheme 1
Scheme 2
Table 1. Trimethylsilylation of alcohols and phenols in solution and under solvent-free conditionsa,b
Entry
Substrate
Silylation in CH3CN
Time=h
Yield=%c
Solvent-free silylation
Time=h
Yield=%c
0.21 90
1
2
3
4
5
6
7
8
Benzyl alcohol
2-Bromobenzyl alcohol
2-Chlorobenzyl alcohol
4-Chlorobenzyl alcohol
2-Nitrobenzyl alcohol
3-Nitrobenzyl alcohol
4-Nitrobenzyl alcohol
2-Methylbenzyl alcohol
4-tert-Butylbenzyl alcohol
4-Benzyloxybenzyl alcohol
3,4-Methylenedioxybenzyl alcohold
1-Phenylethanol
1.7
2
1.9
2
70
60
60
55
85
87
85
60
50
60
85
72
75
70
60
60
75
70
80
80
70
0.17
0.2
90
95
90
95
90
90
80
90
85
90
80
85
95
85
80
80
88
90
85
82
0.18
0.25
0.25
0.28
0.25
0.23
0.25
0.22
0.4
0.5
0.5
0.4
2.2
2.7
1.7
0.3
1.3
0.83
2.3
2.1
2.2
0.7
1.2
2.2
0.5
2.5
0.5
0.7
0.25
0.73
1
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Benzhydrold
0.7
3-Phenyl-1-propanol
2-Phenyl-1-propanol
1-Phenyl-2-propanol
Cyclohexanol
0.15
0.18
0.3
0.32
0.7
0.72
0.33
0.5
(ꢁ)-Menthold
2-Adamantanold
Cholesterold
1-Adamantanold
e
e
Cinnamyl alcohol
Phenol
2-Chlorophenol
–
0.3
–
90
90
85
60
80
60
0.17
0.12
0.25
0.42
0.2
95
93
95
95
95
90
2,4-Dichlorophenol
4-Fluorophenol
Hydroquinonef
0.5
2.7
Resorcinolf
0.7
a
Products were identified spectroscopically and also by the conversion of the products to their corresponding starting materials;
Under solvent-free conditions: trimethylsilylation of alcohols and phenols was performed at 90 and 100ꢂC; c Isolated yields;
The reaction was performed using 1.5 mmol of HMDS; e Mixture of products; f Yields are related to the products with two
b
d
protected hydroxyl groups

Fe(HSO4)3 Promoted Trimethylsilylation
19
tiary aliphatic ones) and phenols was investigated in
the absence of solvent by HMDS in the presence of
Fe(HSO4)3 (Table 1). In a simple procedure, a mix-
ture of reactants was stirred in an oil bath (90–
100ꢂC) for the appropriate time (Table 1). Both types
of the above-mentioned compounds reacted effi-
ciently and the corresponding silyl ethers were iso-
lated in good to high yields. No oxidation product
was observed during the course of the reaction.
However, this method is not useful for the silylation
of allylic alcohols (Table 1, entry 22).
In order to compare the obtained results with those
obtained in solution, we studied the silylation in re-
fluxing acetonitrile. As shown in the Table 1, there are
appreciable differences between the results obtained
in solution and those under solvent-free conditions. In
conclusion, by omitting the solvent in addition to ease
of the work-up procedure, the reaction time was re-
duced and the need for solvent is avoided.
Experimental
Chemicals were purchased from Fluka, Merck, and Aldrich
Chemical Companies. All of the trimethylsilyl ethers are
known compounds and were characterized on the basis of
their spectroscopic data (IR and NMR), and by comparison
with those reported in literature [14, 16, 22–25], and also by
regeneration of the corresponding alcohols. All yields refer to
the isolated products. The purity determination of the substrate
and reaction monitoring was executed by TLC on silica-gel
polygram SILG=UV 254 plates.
General Procedure for Silylation of Alcohols and Phenols
in CH3CN
To a mixture of 1 mmol substrate and 0.087g Fe(HSO4)3
(0.25 mmol) in 4 cm3 CH3CN, 0.161 g HMDS (1mmol) was
added dropwise within 5 min with stirring under reflux condi-
tion. After completion of the reaction (TLC or GC), 10cm3
water were added and the organic layer was separated, dried
(MgSO4), and filtered. Evaporation of the solvent gave almost
pure product(s). Further purification proceeded by bulb-to-
bulb distillation under reduced pressure or recrystallization
to afford the pure silyl ether.
Although the actual role of Fe(HSO4)3 is not clear,
on the basis of the previously reported mechanism
for the silylation of alcohols with HMDS in the pres-
ence of Al(HSO4)3 [18] the mechanism that is shown
in Scheme 2 is selected as the most probable one.
To illustrate the efficiency of the proposed meth-
od, Table 2 compares some of our results with some
of those reported for relevant reagents in the litera-
ture [14, 17, 18], which demonstrates its significant
superiority.
In conclusion, the present method demonstrates
that trimethylsilylation of alcohols and phenols with
HMDS is effectively promoted in the presence of
Fe(HSO4)3. The relatively short reaction times, good
to high yields of the products, the simple and clean
work-up, and the mild reaction conditions make this
method a useful addition to the present methodolo-
gies for the silylation of alcohols and phenols.
General Procedure for Silylation of Alcohols and Phenols
under Solvent-Free Conditions
A
mixture of 1 mmol substrate, 0.087 g Fe(HSO4)3
(0.25 mmol) and 0.161g HMDS (1mmol) was shaken in an
oil bath (90–100ꢂC) for the specified time (Table 1). The prog-
ress of the reaction was monitored by TLC. 10cm3 water were
added and the mixture was extracted with 3ꢃ10cm3 diethyl
ether. The organic layer was separated and dried (MgSO4).
Evaporation of the solvent gave almost pure product(s). Fur-
ther purification proceeded by bulb-to-bulb distillation under
reduced pressure or recrystallization to afford pure silyl ether.
Acknowledgement
We are grateful to the Guilan University Research Council for
the partial support of this work.
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