Trimethylsilyl protection of alcohols over phosphorus pentoxide supported on silica gel

Article abstract of DOI:10.1080/10426507.2010.526670

An eco-friendly and mild protocol for trimethylsilyl protection of alcohols over phosphorus pentoxide supported on silica gel using hexamethyldisilazane has been described. Solvent-free and ambient reaction conditions, easy workup, short reaction times, e

Full text of DOI:10.1080/10426507.2010.526670

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Phosphorus, Sulfur, and Silicon and the
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Trimethylsilyl Protection of Alcohols
Over Phosphorus Pentoxide Supported
on Silica Gel
Hamid Reza Shaterian a , Nafiseh Fahimi a & Kobra Azizi a
a Department of Chemistry, Faculty of Sciences , University of Sistan
and Baluchestan , Zahedan , Iran
Published online: 04 Aug 2011.
To cite this article: Hamid Reza Shaterian , Nafiseh Fahimi & Kobra Azizi (2011) Trimethylsilyl
Protection of Alcohols Over Phosphorus Pentoxide Supported on Silica Gel, Phosphorus, Sulfur, and
Silicon and the Related Elements, 186:7, 1604-1611, DOI: 10.1080/10426507.2010.526670
To link to this article: http://dx.doi.org/10.1080/10426507.2010.526670
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Phosphorus, Sulfur, and Silicon, 186:1604–1611, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.526670
TRIMETHYLSILYL PROTECTION OF ALCOHOLS OVER
PHOSPHORUS PENTOXIDE SUPPORTED ON SILICA GEL
Hamid Reza Shaterian, Nafiseh Fahimi, and Kobra Azizi
Department of Chemistry, Faculty of Sciences, University of Sistan and
Baluchestan, Zahedan, Iran
GRAPHICAL ABSTRACT
H
P2O5/SiO2
N
2ROH
+
ROSiMe
3
Me3Si
SiMe3
2
)
(-NH
neat,
r.t,
3
R: Aryl, primary, secondary and tertiary Alkyl
Abstract An eco-friendly and mild protocol for trimethylsilyl protection of alcohols over
phosphorus pentoxide supported on silica gel using hexamethyldisilazane has been described.
Solvent-free and ambient reaction conditions, easy workup, short reaction times, excellent
yields, and reusability of the catalyst are the noticeable features of this methodology.
Keywords Alcohols; hexamethyldisilazane; P2O5/SiO2; trimethylsilylation
INTRODUCTION
Trimethylsilyl protection of alcohols has been recognized as an important part of or-
ganic, inorganic, and analytical chemistry.1 This synthetic methodology was used especially
as a protecting group approach in many multistep syntheses with reasonable complexity
for masking hydroxyl functional groups.2 This transformation enhances solubility in non-
polar solvents, has low viscosity, increases thermal stability, and is resistant to oxidation;
in addition, trimethylsilylation of hydroxyl compounds is used extensively to increase the
volatility of the compounds for gas chromatography and mass spectrometry.3
The preparation of silyl ethers can be carried out by treatment of alcohols with silyl
chlorides in the presence of a stoichiometric amount of an organic base4 or silyl triflates
with R3Si–H activated by dirhodium (II) perfluorooctanoate.5 However, these methods
suffer from drawbacks such as lack of reactivity or the difficulty in removal of amine
salts.4,5 1,1,1,3,3,3-Hexamethyldisilazane (HMDS), an inexpensive and readily available
compound, has been used for the preparation of trimethylsilyl ethers from hydroxyl com-
pounds.6 The only by-product of this reaction is NH3 gas, which is a notable advantage of
Received 11 July 2010; accepted 21 September 2010.
We are thankful to the University of Sistan and Baluchestan Research Council for the partial support of this
work.
Address correspondence to Hamid Reza Shaterian, Department of Chemistry, Faculty of Sciences, University
of Sistan and Baluchestan, P.O. Box 98135-674, Zahedan, Iran. E-mail: hrshaterian@chem.usb.ac.ir
1604

PROTECTION OF ALCOHOLS
1605
the method.6 Even though the handling of this reagent is easy, the low silylation power of
HMDS is the main drawback to its application7; therefore, there are a variety of catalysts to
activate this reagent, such as Envirocat EPZGO,8 tungstophosphoric acid,9 K-10 montmoril-
lonite,10 cupric sulfate pentahydrate,11 lithium perchlorate supported on silica gel,12 sulfonic
acid–functionalized silica,13 magnesium triflate,14 alumina-supported heteropolyoxometa-
lates,15 iron (III) trifluoroacetate,16 silica-supported perchloric acid,17 superparamagnetic
iron oxide,18 barbutric acid,19 and TiCl2(OTf)-SiO2.20 Recently, an uncatalyzed method
for the silylation of alcohols and phenols with HMDS in CH3NO2 was reported.21 Even
though these catalytic systems enhance the ability of HMDS for the silylation, some of the
catalysts require a long reaction time, a high temperature, and an excess amount of reagent.
The lack of a facile and general synthetic methodology under essentially mild reaction
conditions has prompted us to develop an efficient, convenient, and practical procedure for
the silylation of alcohols under solvent-free conditions at room temperature. In the present
research for functional group transformation, we wish to describe a new protocol for the
mild and rapid trimethylsilylation of a wide variety of hydroxyl groups using HMDS and a
catalytic amount of phosphorus pentoxide supported on silica gel (P2O5/SiO2) as a catalyst
at room temperature under solvent-free conditions (Scheme 1).
H
P2O5/SiO2
N
2 ROH
+
2 ROSiMe3
Me3Si
SiMe3
)
(-NH
neat,
r.t,
3
R: Aryl, primary, secondary and tertiary Alkyl
Scheme 1
Phosphorus pentoxide-methanesulfonic acid was used for the first time as a convenient
alternative to polyphosphoric acid by Eaton et al.22 to escape the difficulties encountered
with polyphosphoric acid (PPA). Then, P2O5 supported on SiO2 as an inexpensive, hetero-
geneous, stable, free-flowing, white powder was prepared.23a This compound is safe, easy
to handle, environmentally benign, and presents fewer disposal problems.23 To the best of
our knowledge there has been no report available on trimethylsilyl protections of alcohols
over P2O5/SiO2 as a catalyst in the literature.
RESULTS AND DISCUSSION
To optimize the amount of the catalyst in the mentioned reaction, we carried out
a model study of benzyl alcohols with HMDS in the presence of different amounts of
P2O5/SiO2 (7% w/w)24 as a catalyst under solvent-free conditions at room temperature
(Table 1). It was found that 0.06 g of the catalyst showed a maximum yield (95%) in
minimum a reaction time (3 min). Further increasing the catalyst amount (0.08, 0.1 g)
decreased the yield of the product in 2 min.
Using these optimized reaction conditions, 60 mg of P2O5/SiO2 (7% w/w), the scope
and efficiency of the reaction were explored for the synthesis of a wide range of structurally
diverse and functionalized alcohols, phenols, and naphthols at room temperature (Table 2).
Generally, in all cases of benzylic alcohols, primary, secondary, and tertiary alcohols and
phenols and naphthols were converted to corresponding trimethylsilyl ethers within less

1606
H. R. SHATERIAN ET AL.
Table 1 Optimization amount of the P2O5/SiO2 as a catalyst in the synthesis of benzyl trimethylsilyl ether under
solvent-free and mild conditions
Entry
Amount P2O5/SiO2 (Catalyst) (g)
Time (min)
Yield (%)
1
2
3
4
0.04
0.06
0.08
0.1
8
3
2
2
80
95
90
88
aA molar ratio of benzyl alcohol/HMDS was chosen (1:0.75), and yields refer to isolated pure products.
than 30 min by evolution of NH3 gas from the reaction mixture. There was not much
difference in reactivity with the variation of aliphatic and aromatic compounds containing
hydroxyl functional groups. Only tertiary alcohols (Table 2, entries 16, 17) took a longer
time to complete the reaction, which is due to steric hindrance. Phenols containing an amino
functional group were regioselectively O-silylated (Table 2, entry 19), whereas the amino
group was intact.
To show the merit of the present work in comparison with reported results in the
literature, we compared results of P2O5/SiO2 with Cu(OTf)2,25 Mg(OTf)2,14 cupric sulfate
pentahydrate,11 alumina-supported heteropolyoxometalates,15 and LiClO426 in the synthesis
of trimethyl(phenoxy)silane. As shown in Table 3, P2O5/SiO2 can act as an effective catalyst
with respect to reaction times, amount of the catalyst, and yields of the obtained products.
Thus, the present protocol withP2O5/SiO2 catalyst is convincinglysuperior tosomereported
catalytic methods.
From the context of a green approach, the reusability study of the catalyst was
performed with the O-silyl protection of benzyl alcohol (Table 2, entry 1). After completion
of the reaction (checked by thin-layer chromatography [TLC]), the reaction mixture was
solved using ethylacetate and filtered to separate the catalyst. It was washed well with ethyl
◦
acetate (2 × 5 mL) and then dried at 100 C for 2 h before being further used. It was
observed that on five successive runs with P2O5/SiO2 as the catalyst, the reactivity in all
runs remained almost unchanged (Figure 1).
Figure 1 The reusability study of the P2O5/SiO2 as the catalyst in O-silyl protection of benzyl alcohol.

PROTECTION OF ALCOHOLS
1607
Table 2 Trimethylsilylation of benzylic alcohols; primary, secondary, and tertiary alcohols; and phenols and
naphthols with HMDS in the presence of solid heterogeneous P2O5/SiO2 as a catalyst (0.06 g) under ambient
conditions
Literature
Time
(min)
Yield
(%)a
References for
Entry
1
Substrate
Product
Known Productb
3
4
95
95
16, 17, 27
16, 17
2
3
7
89
16, 17, 27
4
5
8
4
91
97
16, 17, 27
16, 17, 27
6
7
9
85
95
17
27
18
8
9
3
2
92
94
17
17
10
11
4
4
95
88
17
17
12
13
10
15
90
91
17, 27
17, 27
14
15
8
93
95
16, 17, 27
17
15

1608
H. R. SHATERIAN ET AL.
Table 2 Trimethylsilylation of benzylic alcohols; primary, secondary, and tertiary alcohols; and phenols and
naphthols with HMDS in the presence of solid heterogeneous P2O5/SiO2 as catalyst (0.06 g) under ambient
conditions (Continued)
Literature
Time
(min)
Yield
(%)a
References for
Entry
16
Substrate
Product
Known Productb
35
30
89
95
17
17
18
16, 17, 27
3
97
17
19
20
5
3
91
97
17
16, 17, 27
21
22
5
6
91
91
17
16, 17, 27
aA molar ratio of substrate/HMDS was chosen (1:0.75). Yields refer to the pure isolated products.
1
bThe structure of all known products was confirmed by comparison of their spectral data (FTIR and H and
13C-NMR) with those of known samples in the literature.16,17,27
According to our chemical reaction observation and literature survey16–18,21,27 for the
investigated process, the following mechanism can be proposed for this transformation.
According to the evolution of NH3 in the reaction conditions, the interaction between
the acidic nature of P2O5/SiO2 and Lewis base nature of nitrogen (nonbonding electrons)
of HMDS polarizes the N–Si bond to produce the reactive silylating agent (I). A rapid
reaction with alcohol then ensues, leading to the ammonium-silylating species (II) with
concomitant release of the corresponding silyl ether. Irreversible cleavage of (II) with
alcohol leads to ROSiMe3 and formation of (III). The mechanism clearly shows one mole
of HMDS molecule reacting with two moles of alcohols. The P2O5/SiO2-NH3 complex
ends up with the evolution of gaseous ammonia and the recycling of P2O5/SiO2. The
evolution of ammonia was confirmed by its strong, pungent odor and the use of red litmus

PROTECTION OF ALCOHOLS
1609
Table 3 Comparison result of P2O5/SiO2 with Cu(OTf)2,26 Mg(OTf)2,14 cupric sulfate pentahydrate,11 alumina-
supported heteropolyoxometalates,15 and LiClO427 in the silylation of phenol with HMDS
Amount of
Catalyst (g) (min)
Time
Yield
(%)a
Entry
Catalyst
Conditions
1
2
3
4
Cu(OTf)2
Mg(OTf)2
Cupric sulfate pentahydrate
Alumina-supported
heteropolyoxometalates
LiClO4
Solvent (CH3CN), RT
Solvent free, RT
Solvent (CH3CN), RT
Solvent (Toluene), 85 ◦C
0.03
0.03
0.02
0.1
120
60
90
70
70
95
90
100
5
6
Solvent free, RT
Solvent free, RT
0.5
20
3
96
P2O5/SiO2
0.06 (7% w/w)
97 (Present work)
aYields refer to isolated products.
P2O5/SiO2
+
(Me3Si)2NH
(Me3Si)2NH----P2O5/SiO2
ROH
(I)
NH3
ROSiMe3
Me3SiNH2-----P2O5/SiO2
(II)
(III)
H3N-----P2O5/SiO2
ROSiMe3
ROH
Scheme 2
paper. Released P2O5/SiO2 as catalyst from intermediate (III) reenters catalytic cycle
(Scheme 2).
P2O5/SiO2 has improved storage stability in moisture in comparison to P2O5, which
is very sensitive to moisture and showed much more reactivity than unsupported P2O5.23
P2O5/SiO2 can react with ammonia in an acid–base interaction, but gaseous ammonia is
an excellent driving force for easy cleavage of P2O5/SiO2-NH3 and recycling the catalyst
for continuation catalytic cycle in the mechanism. Finally, P2O5/SiO2, a heterogeneous
catalyst, was removed from the organic product by simple filtration.
CONCLUSION
In summary, we have demonstrated that P2O5/SiO2 is a new, efficient, and heteroge-
neous catalyst for trimethylsilylation of a variety of hydroxyl groups using HMDS under
solvent-free, mild, and ambient conditions. The reactions were carried out at room tem-
perature with a short reaction time and produce the corresponding trimethylsilyl ethers in

1610
H. R. SHATERIAN ET AL.
good to excellent yields. The catalyst can be recovered from reaction mixtures by a simple
filtration procedure and reused.
EXPERIMENTAL
All reagents were purchased from Merck and Aldrich and used without further
purification. P2O5/SiO2 was prepared according to the reported procedure.24 All yields
refer to isolated products after purification. Products were characterized by comparison
with authentic samples and by spectroscopy data (Fourier transform infrared [FTIR] and
1H-NMR and 13C-NMR spectra). The nuclear magnetic resonance (NMR) spectra were
recorded on a Bruker Avance DPX 500 MHz instrument. The spectra were measured in
CDCl3 relative to tetramethylsilane (TMS; 0.00 ppm). FTIR spectra were recorded on a
Jasco FTIR 460 plus spectrophotometer. TLC was performed on silica-gel polygram SIL
G/UV 254 plates.
General Procedure for Trimethylsilylation of Alcohols Using HMDS
Catalyzed with P2O5/SiO2
To a stirred solution of alcohols (10 mmol) and HMDS (7.5 mmol) was added
P2O5/SiO2 (0.6 g) and the mixture was stirred at room temperature for the time specified in
Table 2. The reaction was followed by TLC (n-hexane-EtOAc, 9:1). After completion of the
reaction (checked by TLC), the reaction mixture was solved using ethyl acetate and filtered
to separate the catalyst. It was washed well with ethyl acetate (2 × 5 mL) and then dried
at 100 ◦C for 2 h before being further used. Then, the filtered solution was evaporated and
purified by passing through a short pad column of silica gel using n-hexane as eluent (2 ×
20 mL). Evaporation of the solvent under reduced pressure gave pure product(s) (Table 2).
The desired pure product(s) were characterized by comparison of their physical data with
those of known compounds.16,17,27
Selected Spectral Data
1
Trimethyl(benzyloxy) silane (Table 2, entry 1): colorless liquid, H-NMR (CDCl3,
500 MHz): δ = 7.36–7.35 (5H, m), 4.72 (2H, s), 0.18 (9H, s) ppm; 13C-NMR (CDCl3,
125 MHz): δ = 138.32, 128.36, 127.45, 127.35, 67.85, 0.29; IR (CCl4): 2957, 1496, 1454,
1377, 1250, 1207, 1096, 1027, 842, 727, 695 cm−1
.
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