Silylation of alcohols and phenols with hexamethyldisilazane over highly reusable propyl sulfonic acid functionalized nanostructured SBA-15

Article abstract of DOI:10.1016/S1872-2067(10)60300-2

Various alcohols and phenols were trimethylsilylated in excellent yields using hexamethyldisilazane in the presence of catalytic amounts of environmentally friendly, hydrophobic, highly thermal stable, and completely heterogeneous sulfonic acid functionalized mesostructured SBA-15 in dichloromethane at ambient temperature. Primary, bulky secondary, tertiary, and phenolic hydroxyl functional groups were transformed to the corresponding trimethylsilyl ethers in excellent yields. The simple experimental procedure was accompanied by easy recovery and the catalyst was reusable (at least 18 reaction cycles); these are attractive features of this protocol.

Full text of DOI:10.1016/S1872-2067(10)60300-2

CHINESE JOURNAL OF CATALYSIS
Volume 32, Issue 12, 2011
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2011, 32: 1864–1868.
RESEARCH PAPER
Silylation of Alcohols and Phenols with
Hexamethyldisilazane over Highly Reusable Propyl Sulfonic
Acid Functionalized Nanostructured SBA-15
Daryoush ZAREYEE*, Rezvaneh ASGHARI, Mohammad A. KHALILZADEH
Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
Abstract: Various alcohols and phenols were trimethylsilylated in excellent yields using hexamethyldisilazane in the presence of catalytic
amounts of environmentally friendly, hydrophobic, highly thermal stable, and completely heterogeneous sulfonic acid functionalized
mesostructured SBA-15 in dichloromethane at ambient temperature. Primary, bulky secondary, tertiary, and phenolic hydroxyl functional
groups were transformed to the corresponding trimethylsilyl ethers in excellent yields. The simple experimental procedure was accompa-
nied by easy recovery and the catalyst was reusable (at least 18 reaction cycles); these are attractive features of this protocol.
Key words: reusable heterogeneous catalyst; solid sulfonic acid; SBA-15; protecting group; silylation; hexamethyldisilazane
The protection of the hydroxyl function in alcohols and
phenols is a common and versatile part of many syntheses of
reasonable complexity. Among the routinely employed meth-
odologies for the masking of hydroxyl groups in organic
chemistry, the transformation of alcohols to the corresponding
silyl ethers is a popular procedure [1,2]. The popularity and
extensive use of silyl ethers as protecting groups for alcohols
come from their ease of formation, resistance to oxidation,
good stability toward most non-acidic reagents, and easy de-
protection to provide free alcohols [3]. Although many re-
agents are available for the silylation of hydroxyl groups
[4–13], some of these methods suffered from serious draw-
backs such as the lack of reactivity, low product yields, long
reaction times, expensive reagents and catalysts, and robust
purification steps or difficulty in by-product removal. In con-
trast, 1,1,1,3,3,3-hexamethyldisilazane (HMDS) is a cheap,
easy handling, commercially available and stable reagent, and
it is frequently used for the trimethylsilylation of hydroxyl
groups giving ammonia as the only by-product. However, the
main drawback of HMDS is its poor silylating power as it
needs forceful conditions and long reaction times in many
instances [14]. Therefore, a variety of catalysts have been
developed for the activation of this reagent such as sulfuric acid
[2], (CH3)3SiCl [15], sulfonic acids [16], K-10 montmorillonite
[17,18], iodine [19], tungstophosphoric acid (H3PW12O40) [20],
LiClO4 [21], TBBDA and PBBS [22], [PdCl(Ș3-C3H5)]2-PPh3
[23], HReO4 [24], LaCl3 [25], tribromomelamine [26],
Bi(OTf)3 [27], tribromoisocyanuric acid and DABCO-Br [28].
Although the silylation ability of HMDS has been improved by
these methods, some problems such as the use of a corrosive
catalyst, drastic reaction conditions, tedious workup, and long
reaction times still need to be overcome. Moreover, many of
these reagents are expensive and non-recoverable leading to
the generation of a large amount of toxic waste particularly
when large-scale applications are considered. In other words,
the tightening of legislation with regard to the treatment and
disposal of toxic waste produced during the difficult separation
of the desired products is forcing industry to consider greener
technologies. Therefore, solid acids catalysis is a growing field
of research as the demand for clean and eco-friendly chemical
processes is increasing [29–34]. Accordingly, chemical indus-
try is currently searching for highly active, stable, and recy-
clable solid acids to improve the environmental safety of the
production of chemicals under milder reaction conditions. To
address these issues, Zareyee and Karimi [35] demonstrated
the application of recoverable sulfonic acid functionalized
ordered mesoporous silica (MCM-41-Pr-SO3H) for the effi-
cient silylation of alcohols and phenols. Quite recently, they
Received 6 July 2011. Accepted 3 November 2011.
*Corresponding author. Tel: +98-123-214-5048; Fax: +98-123-214-5050; E-mail: zareyee@gmail.com, zareyee.d@qaemshahriau.ac.ir
Copyright © 2012, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(10)60300-2

Daryoush ZAREYEE et al. / Chinese Journal of Catalysis, 2011, 32: 1864–1868
used a heterogeneous and hydrophobic sulfonic acid nanore-
actor with acidic sites and phenyl groups within the
mesochannel of SBA-15 as an efficient, environmentally be-
nign, and highly recoverable catalyst for the Pechmann [36]
and Strecker [37] reactions. In the course of our ongoing green
organic chemistry program and current interest in the devel-
opment of nanostructured solid acids for different organic
transformations [35–39], we report on a brief preparation and
application of a sulfonic acid nanoreactor (SBA-15-Ph-Pr-
SO3H) for the trimethylsilylation of hydroxyl groups.
R-Si(OEt)3
Toluene, reflux, 48 h
= CH2CH2CH2SH
= C6H5
Oxidation
= CH2CH2CH2SO3H
1 Experimental
1.1 Preparation of SBA-15-Ph-Pr-SO3H
The synthesis of SBA-15-Pr-SH was achieved using the
known procedure described by Stucky et al. [40]. This proce-
dure involved a synthetic strategy based on the co-con- densa-
tion of tetraethoxysilane (TEOS) and 3-mercaptopro- pyl-
trimethoxysilane (MPTMS) in the presence of Pluronic P123
as the structure directing agent. In a typical preparation pro-
cedure, 4 g of Pluronic P123 (Aldrich, average Mw = 5800) was
dissolved in 125 g of 1.9 mol/L HCl solution with stirring at
room temperature. The solution was heated to 40 °C before
adding 6.83 g TEOS. After a 3 h pre-hydrolysis of TEOS, 1.6 g
thiol precursor MPTMS was added. The resultant solution was
stirred for 20 h at 40 °C after which the mixture was aged at
100 °C for 24 h under static conditions. The solid was recov-
ered by filtration and air dried at room temperature overnight.
The template was removed from the as-synthesized material by
washing with ethanol using a Soxhlet apparatus for 24 h.
To a suspension of SBA-15-Pr-SH (3 g) in dry toluene
PhSi(OEt)3 (PTES, 4 mmol) was added. The resulting mixture
was first stirred at room temperature for 1 h and then refluxed
for a further 24 h. The solid material was filtered and succes-
sively washed with toluene, EtOH, and Et2O and dried over-
night at 120 °C to afford the corresponding SBA-15-Ph-Pr-SH.
Conversion of the catalyst's thiol groups to sulfonic acid
moieties was accomplished by hydrogen peroxide. Typically,
0.3 g of solid hydrophobic material was suspended in 10 g of
aqueous 30 wt% H2O2. This suspension was stirred at room
temperature in an Ar atmosphere for 24 h. After the oxidation
treatment, the resulting solution was filtered and washed
separately with water and ethanol. Finally the wet material was
suspended in 1 mol/L H2SO4 solution for 2 h and it was then
washed several times with water and ethanol and dried at 60 °C
under vacuum overnight to give the corresponding
SBA-15-Ph-Pr-SO3H, denoted as catalyst 1 (Fig. 1).
Fig. 1. Schematic representation of the preparation of the sulfonic acid
based catalyst 1.
decreased to 2.19
1.2 General procedure for the trimethylsilylation of
alcohols
To a solution of alcohol (1 mmol) and HMDS (0.6 mmol) in
dichloromethane (3 ml) catalyst 1 (19 mg, 3 mol%) was added.
The mixture was stirred at 35 °C for a period of time (Fig. 2).
Reaction progress was monitored by thin layer chromatogra-
phy (TLC) and gas chromatography (GC). After the comple-
tion of the reaction the product was isolated by filtration.
Evaporation of the solvent under reduced pressure gave the
RꢀOH
+
HMDS
+
CH2Cl2
RꢀOSiMe3
The concentration of sulfonic acid groups in catalyst 1 was
quantitatively estimated by ion-exchange pH analysis. To an
aqueous solution of NaCl (1 mol/L, 25 ml) with a primary pH
of 5.1 the catalyst 1 (100 mg) was added and the resulting
mixture was stirred for 6 h after which the pH of the solution
Fig. 2. Silylation reaction using catalyst 1.

Daryoush ZAREYEE et al. / Chinese Journal of Catalysis, 2011, 32: 1864–1868
corresponding silyl ether.
Table
1
Trimethylsilylation of alcohols and phenols using
SBA-15-Ph-Pr-SO3H in dichloromethane at 35 °C
2 Results and discussion
2.1 Acid amount of SBA-15-Ph-Pr-SO3H
Time Yield*
(min) (%)
Entry
Substrate
OH
OH
Product
OTMS
OTMS
1
2
20
100
The amount of acid in SBA-15-Ph-Pr-SO3H was determined
to be 1.61 mmol/g. CHN and thermal gravimetry (TG) analysis
(Fig. 3) of the catalyst confirms an acid content of 1.61
mmol/g.
30
97
Cl
Cl
OH
OTMS
3
4
40
50
96
99
Cl
Cl
Cl
Cl
2.2 Trimethylsilylation of alcohols and phenols
OH
OH
OTMS
OTMS
Cl
Cl
As
a preliminary study, the catalytic evaluation of
5
6
50
93
80
SBA-15-Ph-Pr-SO3H towards the synthesis of silyl ether from
benzyl alcohol was undertaken.
H3C
O2N
H3C
O2N
OH
OH
OTMS
OTMS
OTMS
150
In an initial attempt, a blank reaction was carried out using 1
equiv. each of benzyl alcohol and HMDS in the presence of 1
mol% (6.3 mg) of SBA-15-Ph-Pr-SO3H. These were stirred at
room temperature in CH2Cl2 and the corresponding benzy-
loxytrimethyl silane was obtained in 50% GC yield after stir-
ring the reaction mixture for 180 min. Increasing the reaction
temperature to 35 °C improved the yield of the related product
to 80% under the same reaction conditions. Subsequently, to
establish the best reaction conditions the same reaction be-
tween benzyl alcohol and HMDS in CH2Cl2 at 35 °C was used
as a model reaction to screen the effect of catalytic amounts of
SBA-15-Ph-Pr-SO3H. The results showed that no appreciable
reaction occurred when benzyl alcohol and HMDS were al-
lowed to react in dichloromethane in the absence of a catalyst
and the reaction yield was only 20% of expected product after 2
h without a catalyst. This indicates that the catalyst is required
for this reaction. Interestingly, 3 mol% of catalyst 1 and 0.6
mmol of HMDS was sufficient to drive the silylation of benzyl
alcohol completely over a short reaction time (100% GC yield
after 20 min.). Based on these findings and to ascertain the
scope and generality of this protocol we screened a range of
alcohols and phenols under optimized reaction conditions. As
shown in Table 1, a wide range of alcohols underwent silylation
by this procedure to provide trimethylsilyl ether in excellent
7
8
90
99
91
OH
120
O
O
9
120
89
OH
OH
OH
OH
OTMS
OTMS
10
11
12
150
150
180
90
96
95
OTMS
OTMS
OH
OTMS
OTMS
13
14
180
120
89
90
OH
OH
OH
OTMS
OTMS
15
16
135
135
91
93
t-Bu
t-Bu
OH
OTMS
17
110
95
OH
OTMS
OTMS
18
19
120
160
94
92
OH
100
95
90
85
80
75
70
Cl
Cl
OH
OTMS
20
21
22
300
150
70
80
NO2
NO2
H3C
OH
H3C
OTMS
CH3
CH3
200
90
40
OH
(Ph)3COH
OTMS
(Ph)3COTMS
0
100 200 300 400 500 600 700 800
Temperature (oC)
23
1440
*GC yield.
Fig. 3. TG diagram for SBA-15-Ph-Pr-SO3H.

Daryoush ZAREYEE et al. / Chinese Journal of Catalysis, 2011, 32: 1864–1868
Table 2 Comparison of the catalytic efficiency of SBA-15-Ph-Pr-SO3H with other reported catalysts for the trimethylsilylation of benzyl alcohol using
HMDS
Entry
Catalyst (amount)
SBA-15-Ph-Pr-SO3H (3 mol%)
H3PW12O40 (1 mol%)
LiClO4 (50 mol%)
Solvent
CH2Cl2
Temperature (oC)
Time (min)
Yield (%)
100
100
99
Ref.
this work
[18]a
1
2
3
4
5
6
7
35
55–60
rt
20
23
solvent free
solvent free
CH2Cl2
25
[19]a
LaCl3 (10 mol%)
rt
180
120
4
91
[23]a,b
[18]a,b
[25]a,b,c
[28]a,d
HY Zeolite (0.1 g)
solvent free
solvent free
CH3CN
55–60
rt
80
Bi(OTf)3 (5 mol%)
99
DABCO-Br (0.1 mol%)
rt
10
100
aNo recovery. bLong reaction time. c1 mmol HMDS was used. d0.8 mmol HMDS was used.
yields. Benzylic, primary, hindered and unhindered secondary,
and unhindered tertiary alcohols were silylated in dichloro-
methane at 35 °C and the reactions were completed over pe-
riods ranging from 20 to 1440 min to provide good to excellent
yields of the silylated products (Table 1). In the case of primary
benzylic and aliphatic alcohols the reactions were complete
within 150 min in CH2Cl2 at 35 °C accompanied by a fast
evolution of NH3 gas from the reaction mixture (Table 1, en-
tries 1–11). Various benzyl alcohols with electron-donating and
electron-withdrawing substituents underwent smooth silylation
with excellent yields (Table 1, entries 1–6). The catalytic sys-
tem is applicable to heterocyclic alcohols such as furfuryl
alcohol (Table 1, entry 9). The reaction of primary aliphatic
alcohols proceeded in short reaction time with excellent yields
(Table 1, entries 10 and 11).
benzyl alcohol with HMDS. After the completion of the first
run, which affords the corresponding benzyloxytrimethyl si-
lane in 100% yield, the products and the solvent were removed
from the reaction mixture using a syringe, and fresh reactants
and solvent were added to the catalyst to run the second sily-
lation reaction. Gratifyingly, SBA-15-Ph-Pr-SO3H was suc-
cessfully reused in eighteen successive runs and exhibited
consistent activity to afford an average yield of 99.5% with
virtually no significant loss of performance, which clearly
demonstrates the practical recyclability of this catalyst. This
reusability demonstrates the high stability and turnover of the
catalyst under the conditions employed.
To compare the catalytic potential of catalyst 1 with some
recently reported catalysts, we studied the silylation of benzyl
alcohol using HMDS in the presence of various catalysts (Table
2). The results show that some protocols took longer, some
used dangerous materials with reduced isolated yields and
some used non-recoverable catalysts, which clearly shows that
SBA-15-Ph-PrSO3H should be considered one of the best
choices.
From Table 1, this method is also shown to be efficient for
the silylation of secondary aliphatic (Table 1, entries 12–16)
and aromatic (Table 1, entry 17) alcohols. Phenol and its de-
rivatives were also silylated in an efficient manner in excellent
yields (Table 1, entries 18–21). These encouraging results
prompted us to test the trimethylsilylation of hindered tertiary
alcohols. Even though 1-adamantanol was converted to the
corresponding silylated product in good yield (Table 1, entry
22), for the less reactive triphenylmethanol longer reaction
time was necessary to afford the desired product. However,
triphenylmethanol gave the related trimethylsilyl ether in 40%
yield after 24 h (Table 1, entry 23). For the hindered secondary
and tertiary alcohols no elimination of by-products were ob-
served.
3 Conclusions
SBA-15-Ph-Pr-SO3H was a highly efficient and recoverable
catalyst for the silylation of alcohols and phenols by HMDS in
dichloromethane at 35 °C. The most striking features of this
method are excellent catalytic capacity, outstanding stability,
exceedingly simple workup, and multiple reuse of
SBA-15-Ph-Pr-SO3H. As a consequence, this system repre-
sents a substantial improvement over previous methods
wherein product separation produces a large amount of waste.
In addition, by this method, primary, bulky secondary, tertiary,
and phenolic hydroxyl functional groups are protected with
excellent yields. Further studies will focus on the exploration
of this solid sulfonic acid for other types of functional group
transformations.
After achieving this favorable result, we compared the re-
sults of the silylation of alcohols with our previously reported
catalyst (MCM-41-Pr-SO3H) to determine the effectiveness of
this catalyst. Our evaluation showed that the higher conversion
of starting materials for catalyst 1 in comparison to MCM-41-
Pr-SO3H was likely due to the larger pore size of SBA-15 and
the beneficial influence of phenyl groups in close proximity to
the sulfonic acid groups. Based on these observations it is clear
that the pore size and the hydrophobic character of catalyst 1 is
crucial for the effectiveness of this sulfonic acid based catalyst
for the catalysis of the silylation reaction.
Acknowledgments
The authors acknowledge the Islamic Azad University of
Qaemshahr Research Councils for supporting this work.
Recycling of the catalyst was explored upon the silylation of

Daryoush ZAREYEE et al. / Chinese Journal of Catalysis, 2011, 32: 1864–1868
19 Karimi B, Golshani B. J Org Chem, 2000, 65: 7228
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