P2O5/SiO2 as an efficient and mild catalyst for trimethylsilylation of alcohols using hexamethyldisilazane

Article abstract of DOI:10.1080/15533174.2012.682686

The protection of alcohols with hexamethyldisilazane (HMDS) in the presence of P₂O₅/SiO₂ at very mild and ambient condition with short reaction times is accomplished in excellent yields. P ₂O₅/SiO

Full text of DOI:10.1080/15533174.2012.682686

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Synthesis and Reactivity in Inorganic, Metal-Organic,
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P2O5/SiO2 as an Efficient and Mild Catalyst
for Trimethylsilylation of Alcohols Using
Hexamethyldisilazane
Hossein Eshghi a , Mohammad Rahimizadeh a , Zohreh Ghadamyari a & Ali Shiri a
a Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, I.
R. Iran
Accepted author version posted online: 01 Aug 2012.Published online: 05 Oct 2012.
To cite this article: Hossein Eshghi , Mohammad Rahimizadeh , Zohreh Ghadamyari & Ali Shiri (2012) P2O5/SiO2 as an Efficient
and Mild Catalyst for Trimethylsilylation of Alcohols Using Hexamethyldisilazane, Synthesis and Reactivity in Inorganic, Metal-
Organic, and Nano-Metal Chemistry, 42:10, 1435-1439, DOI: 10.1080/15533174.2012.682686
To link to this article: http://dx.doi.org/10.1080/15533174.2012.682686
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 42:1435–1439, 2012
Copyright ꢀ Taylor & Francis Group, LLC
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ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2012.682686
P2O5/SiO2 as an Efficient and Mild Catalyst for
Trimethylsilylation of Alcohols Using Hexamethyldisilazane
Hossein Eshghi, Mohammad Rahimizadeh, Zohreh Ghadamyari, and Ali Shiri
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, I. R. Iran
CuSO4.5H2O,[16] Cu(OTf)2,[17] LiClO4,[18] Mg(OTf)2,[19] sul-
fonic acid-functionalized nanoporous silica,[20] iodine,[21] and
The protection of alcohols with hexamethyldisilazane (HMDS)
in the presence of P2O5/SiO2 at very mild and ambient condi-
tion with short reaction times is accomplished in excellent yields.
P2O5/SiO2 catalyst is an efficient solid acid and heterogeneous cat-
alyst for this transformation and easily recovered and reused for
several times without significant decrease in its activity. Selectiv-
ity studies showed competitive reaction of primary alcohols over
secondary alcohols and phenols.
LaCl3.[22]
Considering these reports and in continuation of our previous
works,[23–30] we decided to study the application of P2O5/SiO2
as an inexpensive and easily prepared solid acid catalyst on the
protection of alcohols by HMDS as silylating agents (Scheme 1).
P2O5 / SiO2
Keywords HMDS, hydroxyl group, protection, trimethylsilylation
+
HMDS
(R)Ar
OH
(R)Ar
OTMS
CH2Cl2 / rt
SCH. 1. P2O5/SiO2 (1.75 mole %).
INTRODUCTION
Trimethysilylation of hydroxyl groups is one of the most
important strategy for the protection of alcohols.[1] Organosilyl
ethers are stable under various conditions, soluble in nonpolar
solvents, have high thermal stability, and can be easily con-
verted to corresponding alcohols under acid or base hydrolytic
conditions.[2] They help to increase the volatility for analysis in
gas-chromatography and mass spectrometry.[3]
On the other hand, the increasing interest in heterogeneous
catalytic systems have made them important in industry and
organic chemistry.[4] These systems have many advantages such
as simple experimental procedures, mild reaction conditions,
and minimum chemical wastes in comparison with liquid-phase
reactions.[5] Solid acid catalysts are easier to handle, holding
more acidity, and their separation from the products is easier.
Although there are some silylating agents for protection of
hydroxyl group,[6–11] the use of hexamethyldisilazane (HMDS)
as a silylating agent removes some of the difficulties that a
researcher may focus with them. HMDS is nearly neutral, sta-
ble, inexpensive, and easy to handle. The only byproduct is
ammonia, which can be easily removed. A variety of cata-
lysts are used to enhance the silylating power of this reagent
such as silica chloride,[12] Al(HSO4)3,[13] Al(OTf)3,[14] ZrCl4,[15]
EXPERIMENTAL
Protection of Benzyl Alcohol (Typical Procedure)
P2O5/SiO2 (5 mg, 1.75 mole% based on benzyl alcohol) was
added to a solution of benzyl alcohol (1 mmol, 0.108 g) and
HMDS (0.7 mmol, 0.113 g) in dry CH2Cl2 (5 ml). The mixture
was stirred for 5 min. at room temperature and then filtered.
The column chromatography of the filtrate on silica gel using n-
hexane: ethyl acetate (7:3) as eluent yielded the silylated alcohol
in 99% yield.
RESULTS AND DISCUSSION
P2O5/SiO2 was prepared according to our previous published
method.[31] During this research, in order to get an insight into
the solvent effect on the yields and the reaction times, we per-
formed a set of preliminary experiments on the silylation of
benzyl alcohol as a model experiment in different solvents such
as THF, CH3CN, CH2Cl2, CHCl3, MeOH, and EtOH. The best
results (99% yield in 5 min reaction time) were achieved when
CH2Cl2 was used as the reaction media (Table 1).
Also, to obtain the best molar ratio of catalyst, the model
reaction performed with different amounts of catalyst. The ob-
tained results showed using 5 mg of catalyst (1.75 mole %) per
1 mmol of substrate obtained the best yield.
Received 12 September 2011; accepted 31 March 2012.
Address correspondence to Hossein Eshghi, Department of Chem-
istry, Faculty of Sciences, Ferdowsi University of Mashhad, 91775-
1436 Mashhad, I. R. Iran. E-mail: heshghi@um.ac.ir
Various substituted alcohols were subjected into the reaction
conditions in the presence of 5 mg of P2O5/SiO2 in CH2Cl2
as solvent to give the desired protected compounds 1–14. All
1435

1436
H. ESHGHI ET Al.
TABLE 1
the substrates depicted in Table 2 were successfully reacted at
room temperature in a relatively short period of time, giving the
excellent yield of product.
The optimization of solvent on time and yield of the typical
reaction of benzyl alcohol and HMDSa
The results showed the efficiency of this method. The sub-
strates that were trimethylsilylated by this method are primary,
secondary, allylic, benzylic, and hindered alcohols. Generally,
in the case of primary alcohols, the reactions were completed
within less than 15 min in CH2Cl2 at room temperature with
excellent yields. This method is also applicable for protecting
of relatively unreactive and steric-hindered alcohols such as
benzhydrol (entry 7). In this method, phenol and its electron-
donating derivatives were converted into their corresponding
trimethylsilylated products in low yield while phenols with
electron-withdrawing substituents failed in this reaction (entries
12–16).
Entry
Solvent
Time (min)
Yieldb (%)
1
2
3
4
5
6
THF
CH3CN
CH2Cl2
CHCl3
MeOH
EtOH
30
40
5
10
60
50
80
85
99
95
75
80
aBenzyl alcohol (1 mmol), HMDS (0.7 mmol), and catalyst (5 mg,
1.75 mole %) in CH2Cl2 (5 mL).
bIsolated yields.
TABLE 2
Trimethylsilylation of various alcohols with P2O5/SiO2
a
Entry/Compound
Numbers
Substrate
Product
OTMS
Time (min)
10
Yield (%)b
99
1
OH
2
5
15
10
98
96
98
OH
OTMS
OTMS
H3CO
H3CO
3
4
OH
O2N
O2N
O2N
O2N
OH
OH
OTMS
5
6
15
20
95
95
OTMS
OH
OH
OTMS
7
30
88
OTMS
(Continued on next page)

TRIMETHYLSILYLATION OF ALCOHOLS USING P2O5/SIO2
1437
TABLE 2
Trimethylsilylation of various alcohols with P2O5/SiO2a (Continued)
Entry/Compound
Numbers
Substrate
Product
OTMS
Time (min)
5
Yield (%)b
8
97
OH
9c
15
90
OH
OTMS
HO
TMSO
H3C
10
11
12
20
20
94
92
30
OH
OTMS
H3C
4
4
5
OH
OTMS
H3C
H3C
5
120
OH
OTMS
13
14
100
120
45
35
OH
OTMS
H3CO
H3C
H3CO
H3C
OH
OTMS
OH
15
16
No reaction
—
—
—
—
Cl
OH
No reaction
O2N
aReaction conditions: substrate (1 mmol), HMDS (0.7 mmol), P2O5/SiO2 (5 mg per 1 mmol of substrate), CH2Cl2 (5 mL).
bIsolated yield.
cReaction performed with 1 mmol of substrate and 2 mmol of HMDS.
To explore the selectivity of this method, we have studied
One of the special features of the P2O5/SiO2 catalyst is its
the competitive reaction for trimethylsilylation with a mixture insolubility in organic solvents, which makes its recovery very
of primary and secondary alcohols. The reaction was performed convenient. Therefore, the reusability of the catalyst was also
with benzyl alcohol, 1-phenyl-1-ethanol, HMDS (1 mmol of examined under the optimized reaction conditions with benzyl
each substrates), and P2O5/SiO2. The result showed benzyl alco- alcohol and HMDS as a model reaction. For each of the repeated
hol as a primary alcohol was protected while 1-phenyl-1-ethanol reactions, the catalyst was recovered and washed with ethyl
as secondary alcohol was intact.
acetate consecutively, and dried before being used for the next

1438
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In summary, this method provides a useful alternative for
preparation of trimethylsilylated alcohols. P2O5/SiO2 is an ef-
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tions, simple procedure, irreversibility, high yield, and stability
of the catalyst. Further investigation on the other aspects of this
heterogeneous catalyst in the synthesis of heterocyclic com-
pounds is in progress in our laboratory.
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