Rapid and highly efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) catalyzed by reusable zirconyl triflate, [ZrO(OTf)2]

Article abstract of DOI:10.1016/j.jorganchem.2008.03.009

In this paper, rapid and efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane in the presence of catalytic amounts of ZrO(OTf)₂ is reported. Primary, secondary and tertiary alcohols as well as phenols were efficiently converted to their corresponding TMS ethers in short reaction times at room temperature. It is noteworthy that this method can be used for chemoselective silylation of primary alcohols in the presence of secondary and tertiary alcohols and phenols.

Full text of DOI:10.1016/j.jorganchem.2008.03.009

Journal of Organometallic Chemistry 693 (2008) 2041–2046
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Rapid and highly efficient trimethylsilylation of alcohols and phenols with
hexamethyldisilazane (HMDS) catalyzed by reusable zirconyl triflate, [ZrO(OTf)2]
a
a
a
Majid Moghadam a, , Shahram Tangestaninejad , Valiollah Mirkhani , Iraj Mohammadpoor-Baltork ,
*
Shahin Chahardahcheric b, Ziba Tavakoli b
a Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
b Department of Chemistry, Azad University, Gachsaran Branch, Gachsaran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
In this paper, rapid and efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane in
the presence of catalytic amounts of ZrO(OTf)2 is reported. Primary, secondary and tertiary alcohols as
well as phenols were efficiently converted to their corresponding TMS ethers in short reaction times at
room temperature. It is noteworthy that this method can be used for chemoselective silylation of primary
alcohols in the presence of secondary and tertiary alcohols and phenols.
Received 24 January 2008
Received in revised form 1 March 2008
Accepted 5 March 2008
Available online 18 March 2008
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Alcohol
Phenol
Trimethylsilyl ether
Hexamethyldisilazane
Zirconyl triflate
1. Introduction
catalysts have been developed for activation of this reagent, such
as (CH3)3SiCl [8], sulfonic acids [9], ZnCl2 [10], K-10 montmoril-
Conversion of hydroxy functional groups to silyl ether groups
is a frequently used protection method both in synthesis of fine
chemicals and natural products [1,2]. Commonly, silyl ethers are
prepared by treatment of hydroxyl compounds with silyl chlo-
rides or silyl triflates in the presence of bases such as imidazole
[3], 4-(N,N-dimethylamino)pyridine [4], N,N-diisopropylethyl-
amine [5] and Li2S [6]. However, some of these silylation methods
suffer from disadvantages such as the lack of reactivity or the dif-
ficulty in removal of amine salts derived from the reaction of by-
product acids and co-bases during the silylation reaction. An alter-
native method for the preparation of silyl ethers from hydroxyl
compounds is to use 1,1,1,3,3,3-hexamethyldisilazane (HMDS) as
silylating agent, because it is a stable, commercially available,
cheap reagent and gives ammonia as the only by-product. On
the other hand, silylation with HMDS is nearly neutral and does
not need special precautions. However, the main drawback of
HMDS is its poor silylating power which needs forceful conditions
and long reaction times in many cases [7]. Therefore, a variety of
lonite [11], LiClO4 [12], H3PW12O40 [13], iodine [14], InBr3 [15],
nitrogen-ligand complexes of metal chlorides [16], zirconium sulf-
ophenyl phosphonate [17], CuSO4 ꢀ 5H2O [18], sulfonic acid-func-
tionalized nanoporous silica [19], MgBr2 ꢀ OEt2 [20], LaCl3 [21]
and poly(N-bromobenzene-1,3-disulfonamide) and N,N,N0,N0-tet-
rabromobenzene-1,3-disulfonamide [22]. Although these proce-
dures provide an improvement, but many of these catalysts or
activators need long reaction times, drastic reaction conditions
or tedious workups, moisture sensitive or expensive. Hence, intro-
duction of new procedures to circumvent these problems is still in
demand.
In this paper, we report a rapid and efficient method for trim-
ethylsilylation of alcohols and phenols with hexamethyldisilazane
catalyzed by ZrO(OTf)2 at room temperature.
2. Experimental
Chemicals were purchased from Fluka and Merck chemical
companies. 1H NMR spectra were recorded in CDCl3 solvent on a
Bruker AM 80 MHz or a Bruker AC 500 MHz spectrometer using
TMS as an internal standard. Infrared spectra were run on a Philips
PU9716 or Shimadzu IR-435 spectrophotometer. All analyses were
performed on a Shimadzu GC-16A instrument with a flame
* Corresponding author. Tel.: +98 913 310 8960; fax: +98 311 668 9732.
E-mail addresses: moghadamm@chem.ui.ac.ir, majidmoghadamz@yahoo.com
(M. Moghadam).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.03.009

2042
M. Moghadam et al. / Journal of Organometallic Chemistry 693 (2008) 2041–2046
ionization detector using silicon DC-200 or Carbowax 20M col-
umns and n-decane was used as internal standard.
tion was stirred for 10 min. The AgCl precipitate was filtered
through a 0.45 lm filter. The ZrO(OTf)2 crystals were obtained by
evaporation of solvent. The catalyst was characterized by FT-IR
and elemental analysis techniques. The FT-IR spectrum of this
catalyst shows bands at 640 (C–S), 1024 (Zr@O), 1168 and 1248
2.1. Preparation of the catalyst
To a solution of ZrOCl2 ꢀ 8H2O (0.646 g, 0.2 mmol) in deionized
(S–O) cmꢁ1
.
water (25 mL), AgCF3SO3 (1.03 g, 0.4 mmol) was added. The solu-
Elemental analysis data: Calcd. C, 5.92; S, 15.82; Zr, 22.51.
Found: C, 5.45; S, 15.44; Zr, 22.35%.
Table 1
2.2. General procedure for the silylation reaction
Silylation of 4-chlorobenzyl alcohol with HMDS and in the presence of zirconium salts
at room temperaturea
To a mixture of alcohol or phenol (1 mmol) and HMDS (2 mmol)
in CH3CN (1 ml) was added ZrO(OTf)2 (0.5 ml%). The mixture was
stirred at room temperature for a specified time (Table 2). The pro-
gress of the reaction was monitored by GC. After completion of the
reaction, the solvent was evaporated, Et2O (15 ml) was added and
then the catalyst was filtered. The filtrates were washed with brine
and dried over Na2SO4 and concentrated under reduced pressure to
afford the crude product, which was confirmed by 1H NMR and IR
spectral data.
Entry
Yield (%)b
ZrCl4
Time (min)
ZrOCl2
ZrO(OTf)2
100
1
2
3
4
5
10
15
27
39
1
2
3
4
13
22
46
a
Reaction conditions: 4-chlorobenzyl alcohol (1 mmol), HMDS (2 mmol), cata-
lyst (1 mol%), CH3CN (1 ml).
b
GC yield.
Table 2
Trimethylsilylation of alcohols and phenols with HMDS catalyzed by ZrO(OTf)2 at room temperaturea
Entry
1
Hydroxy compound
TMS ether
Time (min)
1
Yield (%)b,c
100 (92)
CH2OH
CH2OSiMe3
CH2CH2OSiMe3
CH2CH2CH2OSiMe3
CH2OSiMe3
2
3
4
5
1
1
1
1
100
CH2CH2OH
100
CH2CH2CH2OH
CH2OH
100 (95)
100
Cl
Cl
CH2OH
CH2OSiMe3
MeO
MeO
MeO
MeO
6
7
8
9
1
1
1
1
100
CH2OSiMe3
CH2OSiMe3
CH2OH
CH2OH
100
t-Bu
Br
t-Bu
Br
100 (95)
100
CH2OSiMe3
CH2OH
CH2OSiMe3
CH2OH
N
N

M. Moghadam et al. / Journal of Organometallic Chemistry 693 (2008) 2041–2046
2043
Table 2 (continued)
Entry
10
Hydroxy compound
TMS ether
Time (min)
1
Yield (%)b,c
100
CH2OH
CH2OSiMe3
11
12
1
1
100
100
OSiMe3
OH
OH
OSiMe3
13
14
1
4
100
100
OSiMe3
OH
CHCH3
OH
CHCH3
OSiMe3
15
16
4
3
100
100
OSiMe3
OH
OH
OSiMe3
17
4
100 (96)
OH
OSiMe3
18
19
1
1
100
100
OSiMe3
OSiMe3
OH
OH
20
21
1
4
100
100
CH3
CH3
C CH3
H3C
H3C
C
CH3
OSiMe3
OH
OH
OSiMe3
(continued on next page)

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M. Moghadam et al. / Journal of Organometallic Chemistry 693 (2008) 2041–2046
Table 2 (continued)
Entry
22
Hydroxy compound
TMS ether
Time (min)
1
Yield (%)b,c
100
OSiMe3
OH
23
24
2
4
100
100
OSiMe3
Cl
Cl
OH
OH
Cl
OSiMe3
Cl
25
4
4
100 (94)
100
Br
OH
Br
OSiMe3
26d
Me3SiO
OSiMe3
HO
OH
27d
4
4
100
100
OSiMe3
OSiMe3
OH
OH
28d
OSiMe3
OH
Me3SiO
HO
29
1
100
OH
CH3
OSiMe3
CH3
30
1
100
OSiMe3
OH
H3C
H3C
H3C
H3C
31
32
1
2
100
100
OSiMe3
OH
OH
OSiMe3

M. Moghadam et al. / Journal of Organometallic Chemistry 693 (2008) 2041–2046
2045
Table 2 (continued)
Entry
33
Hydroxy compound
TMS ether
Time (min)
4
Yield (%)b,c
100 (95)
OSiMe3
OSiMe3
a
Reaction conditions: ROH (1 mmol), HMDS (2 mmol), catalyst (0.5 mol%), CH3CN (1 ml).
GC yield.
Yields in the parentheses are isolated yields.
Reaction was performed with 3 mmole of HMDS.
b
c
d
3. Results and discussion
3.1. Silylation of alcohols and phenols with HMDS catalyzed by
ZrO(OTf)2
HMDS
First, we investigated the ability of different zirconium salts for
the silylation of 4-chlorobenzylalcohol with HMDS in CH3CN as
solvent at room temperature. As shown in Table 1, ZrO(OTf)2 is
superior in terms of reaction time and product yield. Under the
same reaction conditions, a wide variety of alcohols were con-
verted completely to their corresponding silyl ether with 2 mmol
of HMDS in the presence of 0.5 mol% of ZrO(OTf)2 at room temper-
ature. When the reaction of 4-chlorobenzyl alcohol was carried out
with 1.4, 1.6 and 1.8 mmol of HMDS, the yields were 75–90%.
While with 2 mmol of HMDS the reaction was completed. The ob-
tained results for silylation of different primary, secondary (includ-
ing aliphatic and aromatic alcohols) and tertiary alcohols showed
that the reaction was immediately completed for all alcohols at
room temperature and no alcohol was detected by TLC or GC (Table
2). In the absence of catalyst, the reaction was much less efficient
for the conversion of alcohols to silyl ethers. In the case of benzylic
alcohols, the nature of substituents had no significant effect on the
yields of silyl ethers.
H
N
+
Me3Si
SiMe3
_
ZrO(OTf)2
ZrO
1
ROH
NH3
R-O-SiMe3
_
ZrO(OTf)2
+
NH2
[H3N-ZrO(OTf)2]
R-O-SiMe3
Me3Si
ROH
The ability of this catalyst in the silylation of phenols with
HMDS was also investigated. The reaction of phenols with HMDS
Scheme 1.
Table 3
Selective silylation of alcohols and phenols catalyzed by ZrO(OTf)2 in CH3CN
Row
ROH
Silyl ether
Time (min)
1
Yield (%)
100
Cl
CH2OH
CH2OSiMe3
Cl
1
1
1
OH
OSiMe3
1
1
100
0
Cl
CH2OH
Cl
CH2OSiMe3
2
OH
OSiMe3
(continued on next page)

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M. Moghadam et al. / Journal of Organometallic Chemistry 693 (2008) 2041–2046
Table 3 (continued)
Row
ROH
Silyl ether
Time (min)
1
Yield (%)
100
Cl
CH2OH
CH2OSiMe3
OSiMe3
Cl
3
1
1
12
OH
100
Cl
CH2OH
Cl
CH2OSiMe3
4
1
0
OSiMe3
Cl
Cl
OH
in the presence of 0.005 molar equivalent of ZrO(OTf)2 in CH3CN, as
solvent, was carried out and the desired silyl ethers were obtained
in excellent yields at room temperature (Table 2, entries 22–35).
The silylation of dihydroxybenzenes such as hydroquinone, pyro-
catechol and resorcinol, was also achieved. The results showed that
all hydroxyl groups were silylated and the desired bis(trimethyl-
silyl ether) were obtained in excellent yields (Table 2, entries 26–
28).
yields, easy work-up, stability, reusability and relatively non-toxic-
ity of the catalyst are noteworthy advantages of this method which
make this procedure as a useful addition to the existing methodol-
ogies for the protection reactions.
Other applications of this catalyst in organic transformations
are under investigated.
Acknowledgement
A probable mechanism has been shown in Scheme 1. In this
mechanism, it is suggested that the Lewis acid–base interaction
between metal triflate and nitrogen in HMDS polarizes N–Si bond
of HMDS to produce a reactive silylating agent (1), which effec-
tively silylates the hydroxyl compounds. The fast evolution of
ammonia gas is a good indication for the proposed mechanism.
The selectivity of this method was also investigated. As shown
in Table 3, primary alcohols were completely converted to the cor-
responding silyl ether in the presence of a secondary or tertiary
alcohols or phenols (Table 3, entries 1, 2 and 4). Also, in a binary
mixture of 4-chlorobenzyl alcohol and 1-hexanol, the benzylic
alcohol was completely converted to the corresponding silylether,
while only a 12% conversion was observed for the aliphatic alcohol
(Table 3, entry 3).
We are thankful to the Center of Excellence of Chemistry of Uni-
versity of Isfahan (CECUI) for financial support of this work.
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4. Conclusion
In this paper, a rapid, efficient and chemoselective method for
the silylation of alcohols and phenols catalyzed by zirconyl triflate,
ZrO(OTf)2, is reported. In addition, short reaction times, excellent