An Effective Approach for the Silylation of Hydroxyl Compounds in Room Temperature Ionic Liquids

Article abstract of DOI:10.1081/SCC-120026356

The room temperature ionic liquid (RTIL) 1-n-butyl-3-methylimidazolium hexafluorophosphate (BMImPF₆) is used as a "green" recyclable alternative to conventional solvents for the silylation of a series of hydroxyl compounds (alcohols and phenols

Full text of DOI:10.1081/SCC-120026356

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An Effective Approach for the Silylation of Hydroxyl
Compounds in Room Temperature Ionic Liquids
Zhen-Yuan Xu a , Dan-Qian Xu a , Bao-You Liu a & Shu-Ping Luo a
a Catalytic Hydrogenation Research Centre , Zhejiang University of Technology , Hangzhou,
Zhejiang, China
Published online: 16 Aug 2006.
To cite this article: Zhen-Yuan Xu , Dan-Qian Xu , Bao-You Liu & Shu-Ping Luo (2003) An Effective Approach for the Silylation
of Hydroxyl Compounds in Room Temperature Ionic Liquids, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:23, 4143-4149, DOI: 10.1081/SCC-120026356
To link to this article: http://dx.doi.org/10.1081/SCC-120026356
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 23, pp. 4143–4149, 2003
An Effective Approach for the Silylation
of Hydroxyl Compounds in Room
Temperature Ionic Liquids
*
Zhen-Yuan Xu, Dan-Qian Xu, Bao-You Liu,
and Shu-Ping Luo
Catalytic Hydrogenation Research Centre, Zhejiang
University of Technology, Hangzhou, Zhejiang, China
ABSTRACT
The room temperature ionic liquid (RTIL) 1-n-butyl-3-methylimi-
dazolium hexafluorophosphate (BMImPF6) is used as a ‘‘green’’
recyclable alternative to conventional solvents for the silylation of
a series of hydroxyl compounds (alcohols and phenols) with
t-butyldimethylchlorosilane (TBDMCS), which has some advantages
such as simplicity of the synthetic procedure, the potential for
recycling of the ionic liquid and the environmentally benign.
*Correspondence: Zhen-Yuan Xu, Catalytic Hydrogenation Research Centre,
Zhejiang University of Technology, 6 Zone Zhaohui, Hangzhou, Zhejiang,
310014, China; E-mail: chrc@zjut.edu.cn.
4143
DOI: 10.1081/SCC-120026356
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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4144
Xu et al.
Key Words: Room temperature ionic liquid; Silylation; Hydroxyl
compound.
Since it was first reported by Corey and Venkatesxarlu in 1972,[1] the
t-butyldimethylsilyl (TBDMS) group has become one of the most widely
used protecting groups for alcohols and phenols, because TBDMS ethers
are easily formed with a variety of reagents, readily removed and are
quite stable for a number of reactions, such as Wittig reaction,
Grignard reaction, Jones reaction, and Saponefication with aqueous of
alcoholic bases.[2] The more common method for the formation of
TBDMS ethers generally utilizes an excess of t-butyldimethylchlorosilane
(TBDMCS) with hydroxyl compounds in the solvent, such as DMF,
THF, or acetonitrile, containing imidazole. Isolation of the silylated com-
pound is performed by aqueous extraction to remove the solvent and
imidazole, followed by crystallization or distillation of the t-butyldi-
methylsilylated product. For many compounds possessing hydroxyl
groups, the TBDMCS/imidazole/DMF method produces corresponding
TBDMS ethers in high yields, but the time required for each reaction may
vary from 1 h to 2 days, or may require elevated temperatures. More
importantly, because isolation of the silylated product requires aqueous
work-up, the crude product always contains t-butyldimethylsilanol
among other impurities which leads to difficulty to get pure product
and, especially, the organic solvent (DMF) is difficult to recover which
causes environmental pollution.
Our recent interest has been in the area of ‘‘green chemistry’’, so the
green modification of the traditional chemical process has become a part
of our research field. Recently, the versatile applications of room tem-
perature ionic liquids (RTILs) in organic synthesis[3] stimulate us to quest
for new synthetic applications of RTILs. The favorable effect of polar
solvents on the silylation[2] encourages us to find the feasibility to proceed
this kind of silylation in RTILs. In this study, we explored the silylation
of TBDMCS with different kinds of alcohols and phenols in RTILs in the
presence of imidazole. The RTILs used here were 1-n-butyl-3-methylimi-
dazolium tetrafluoroborate (BMImBF4), 1-ethyl-3-methylimidazolium
tetrafluoroborate (EMImBF4), N-n-butylpyridium tetrafluoroborate
(BPyBF4) and 1-n-butyl-3-methylimidazolium hexafluorophosphate
(BMImPF6), which were prepared according to the procedures described
in Lit.[4] respectively.
First, we examined the efficiency of different RTILs in the silylation
of n-butyl alcohol (1a), TBDMCS (2), and imidazole (Sch. 1). The result
is summarized in Table 1. As can be seen from Table 1, all of the RTILs

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Room Temperature Ionic Liquids
4145
RTIL, Im
0.5h
n-C H OH + t-BuMe SiCl
n-C H OSi-t-BuMe
4 9 2
4
9
2
3a
1a
2
Scheme 1.
Table 1. Silylation of n-butyl alcohol with TBDMCS in RTIL.a
Entry
RTIL
Yieldb (%)
Purityc (%)
1
2
3
4
BMImPF6
BMImBF4
EMImBF4
BPyBF4
94
93
95
92
98.0
98.5
98.6
98.2
aAll the reactions were run with n-butyl alcohol (5 mmol), TBDMCS (6 mmol) in
2 g RTIL in the presence of imidazole (12 mmol) for 0.5 h at room temperature.
bIsolated yield for crude product.
cCrude product was analyzed by GC.
tested are effective for the silylation. We considered that BMImPF6 might
be the most favorable choice because of two reasons. On the one hand, a
clear two layer formed quickly after reaction and the product can be
easily separated from the reaction mixture by simple decanting or suction
with a syringe. On the other hand, BMImPF6 is insoluble in water, so a
relative pure RTIL can be recovered by washing with water followed by
vacuum drying.
Then, the silylation of a series of alcohols and phenols (1) with
TBDMCS (2) in BMImPF6 were investigated (Sch. 2). Simple stirring
of a mixture of an alcohol or phenol, TBDMCS, imidazole in
BMImPF6 under a N2 atmosphere at room temperature gave, after
isolation, the desired silylated compound. The results are summarized
1
in Table 2. The products were characterized by IR, H NMR, and MS,
which were consistent with the literature data. For the comparison with
literature reported methods, some compared results are also summarized
in Table 2.
The method was found to be general and applicable to primary and
secondary alcohols (Entries 1–6) even to sterically hindered alcohol, e.g.,
diphenylmethanol (Entry 4) can be silylated smoothly by this method.
But when we select a tert-alcohol, the reaction is so sluggish that we
cannot get a pure product even after a long period of time. As for phe-
nols, although the reaction speed is a little slower than that of alcohols,

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4146
Xu et al.
BMImPF6, Im
0.5-2hours
R(OH)n + n t-BuMe2SiCl
R(OSi-t-BuMe2)n
1
3
2
Scheme 2.
Table 2. Silylation of alcohols and phenols with TBDMCS in BMImPF6.
Time Purity Yield
(%)a (%)b
Yield
in Lit. (%)
Entry
Substrate
n-C4H9OH
Product
(h)
1
2
3a
0.5
0.5
2
98
98
97
99
99
99
94
99
97
98
97
97
97
99
98
96
98
94
96
96
97
96
99
95
90
92
93
97
97
98
94
93
92
99
C6H5CH ¼ CHCH2OH 3b
88[5]c
90,[5] 95[6]d
98[7]e
3
cyclo-C6H11OH
(C6H5)2CHOH
C(CH2OH)4
3c
3d
3e
3f
4
1
5
1
6
C6H5CH2OH
C6H5OH
0.5
2
80[5]93[7]89[8]f
92[7]
7
3g
3h
3i
8
p-NO2C6H4OH
o-ClC6H4OH
p-AcOC6H4OH
p-MeC6H4OH
m-MeC6H4OH
o-MeC6H4OH
p-C6H4(OH)2
m-C6H4(OH)2
2
9
2
10
11
12
13
14
15
16
17
3j
2
3k
3l
2
2
3m
3n
3o
2
2
92[7]
2
4-Me-2,6-Br2C6H2OH 3p
Naphthyl-2-OH 3q
2
1
aPurity was analyzed by GC.
bIsolated yield.
cTBDMCS (10 mmol), alcohol (5 mmol), lithium sulfide (7.5 mmol) in acetonitrile,
5–6 h.
dCyclohexanol with allyl-t-butyldimethylsilane at 70–80ꢀC for 2.5 h.
eTBDMCS (2.22 mmol), DBU (2.40 mmol), C6H6 (4 mL), substrate (2.00 mmol)
at room temperature for 3 h.
fTBDMCS (1.1 equiv.), triethylamine (1.2 equiv.), DMAP (0.04 equiv.) in
CH2Cl2, 25ꢀC.
phenols containing various substituents such as nitro, chloro, acetyl, and
methyl groups were successfully reacted. The compounds possessing
several hydroxyl groups, such as pentaerythritol (Entry 5), hydroquinone
(Entry 14), and resorcinol (Entry 15) can be completely silylated when

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Room Temperature Ionic Liquids
4147
excess of TBDMCS used. Also as can be seen from Table 2 (Entries 2, 3,
4, 6, 7, 14) that in comparison with literature reported methods, present
method gives significant rate acceleration and sound yield.
The BMImPF6 can be readily recovered and reused. Usually, after
isolation of the silylated product by decantation or extraction with ethyl
ether, the left BMImPF6 layer can be recycled without further disposal.
And after several times of recycle, the BMImPF6 was washed with water
and followed by vacuum drying. The recovered solvent can be recycled
with no appreciable decrease in yield.
In summary, we have demonstrated that the room temperature ionic
liquid BMImPF6 is surely an alternative to classical molecular solvents
for the silylation of hydroxyl group with TBDMCS in the presence of
imidazole. It can offer good yields in mild conditions within limited time.
The products can be easily separated from reaction mixture by simple
decanting or extraction. Due to the simplicity of the synthetic procedure,
the potential for recycling of the ionic liquid and the benignity to
environment, present method may be more useful in organic synthesis.
Further investigation is still under way in our lab.
EXPERIMENTAL SECTION
All starting materials were commercially available and without
further purification. The room temperature ionic liquid was dried at
120ꢀC in vacuum for at least 4 h before use. Melting point was detected
1
on a b type melting point detector (uncorrected). Infrared and H NMR
spectra were obtained on Bruker Equinox 55 and Bruker Avance 500
(CDCl3, TMS as internal standard) spectrometers. Mass spectrometry
spectra were recorded on a Varian CP 3800/Saturn 2000 GC/MS spectro-
meter. The purity of the products was detected on a ShangFen GC spec-
trometer (capillary column, column temperature 210ꢀC).
Typical Procedure for Compound 3a
n-Butyl alcohol (0.74 g, 10 mmol) was treated under a N2 atmosphere
with TBDMCS (1.80 g, 12 mmol), imidazole (1.63 g, 24 mmol) and
BMImPF6 (4 g) at room temperature. The stirring was continued till all
the substrate was converted by GC detection. After completion of
reaction, two layers formed and the upper clear layer was separated by
either decanting or sucking with a syringe, washed with (2 ꢁ 10 mL)
distilled water and got the crude product as a colorless liquid (1.79 g,

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4148
Xu et al.
purity 98.0%, yield 94.0%). A more pure sample was obtained by distil-
ling the crude product under reduced pressure. 1H NMR (500 MHz,
CDCl3) ꢀ: 3.6 (t, J ¼ 6.5 Hz, 2H, CH2O), 1.50 (m, 2H, CH2), 1.34 (m,
2H, CH2), 0.91 (t, J ¼ 6.5 Hz, 3H, CH3), 0.89 (s, 9H, Me3C), 0.05 (s, 6H,
Me2Si). IR (film): 2956, 2861, 1256, 1041, 836, 783 cmꢂ1. MS (m/z): 189
(M þ 1, trace), 173 (trace), 131 (100), 89 (25), 75 (67). The left ionic liquid
layer can be recycled without further disposal. And after several times of
recycle, the ionic liquid layer was washed with water (3 ꢁ 10 mL) and then
evaporated to remove the water under reduced pressure, the left ionic
liquid can be reused for another several times without apparent effect on
yield.
Typical Procedure for Compound 3j
Under the protection of nitrogen atmosphere, p-acetylphenol (1.36 g,
10 mmol), TBDMCS (1.80 g, 12 mmol), imidazole (1.63 g, 24 mmol), and
BMImPF6 (4 g) were charged successively into a 20 mL round-bottomed
flask with mechanical stirrer. The reaction process was monitored by thin
layer chromatography (TLC, silica 254, elutent, hexane:ethyl acetate, 2:1)
at regular intervals. After completion of the reaction, the mixture was
extracted with (3 ꢁ 10 mL) ether and then the combined ethereal phase
was washed with (3 ꢁ 10 mL) pure water, dried over anhydrous CaCl2 for
1 h, evaporated to remove the solvent got the desired product (2.33 g,
purity 98.0%, yield 93%). A more pure product can be obtained by
crystallization from minimum amount of ethanol. Melting point:
34–36ꢀC. 1H NMR ꢀ: 7.88 (d, J ¼ 8.7 Hz, 2H, H3H5), 6.87 (d,
J ¼ 8.7Hz, 2H, H2H6), 2.55 (s, 3H, CH3CO), 0.99 (s, 9H, Me3C), 0.23
(s, 6H, (CH3)2Si). IR: 3077, 2936, 2859, 1647, 1597, 1505, 1257, 913,
842 cmꢂ1. MS (m/z): 250 (M þ 1, 48), 235 (5), 193 (100), 179 (7), 151
(49), 133 (11), 91 (5).
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Received in Japan May 7, 2003

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