Chemoselective and catalytic trimethylsilylation of alcohols and phenols by 1,1,1,3,3,3-hexamethyldisilazane and catalytic amounts of PhMe 3N+Br3-

Article abstract of DOI:10.1016/S1872-2067(10)60107-6

An efficient procedure for the trimethylsilylation of alcohols and phenols is presented. The combination of 1,1,1,3,3,3-hexamethyldisilazane and a catalytic amount of phenyltrimethylammonium tribromide (PhMe₃N ⁺Br₃^-) was found to be effective for the trimethylsilylation of alcohols and phenols. The protection reaction is very simple and homogenously performed in dichloromethane at room temperature and mild conditions.

Full text of DOI:10.1016/S1872-2067(10)60107-6

CHINESE JOURNAL OF CATALYSIS
Volume 31, Issue 9, 2010
Online English edition of the Chinese language journal
RESEARCH PAPER
Cite this article as: Chin J Catal, 2010, 31: 1103–1106.
Chemoselective and Catalytic Trimethylsilylation of Alcohols
and Phenols by 1,1,1,3,3,3-Hexamethyldisilazane and
–
Catalytic Amounts of PhMe3N+Br3
Arash GHORBANI-CHOGHAMARANI*, Nasrin CHERAGHI-FATHABAD
Department of Chemistry, Faculty of Science, Ilam University, Ilam 69315516, Iran
Abstract: An efficient procedure for the trimethylsilylation of alcohols and phenols is presented. The combination of
1,1,1,3,3,3-hexamethyldisilazane and a catalytic amount of phenyltrimethylammonium tribromide (PhMe3N+Br3 ) was found to be effective
−
for the trimethylsilylation of alcohols and phenols. The protection reaction is very simple and homogenously performed in dichloromethane
at room temperature and mild conditions.
Key words: phenyltrimethylammonium tribromide; alcohol; phenol; protection; trimethylsilylation; hexamethyldisilazane.
Synthetic methodology, as the building block of organic
synthesis, continuously seeks new reagents, better reaction
conditions, and more efficient and selective methods [1]. When
a chemical reaction is to be carried out selectively at one reac-
tive site in a multifunctional compound, the other reactive sites
should be temporarily blocked [2]. Silyl ethers are the most
popular protecting groups for alcohols and phenols in synthetic
organic chemistry and various types of silyl ethers have been
reported [3−5]. Trimethylsilylation is routinely used to protect
alcohols and phenols, especially in steroids, sugars and natural
product synthesis [6]. The silylation of alcohols is an important
process not only as a method to protect alcohols but also for the
synthesis of functional organosilicon compounds [7]. Gener-
ally, silyl ethers can be synthesized by the reaction of alcohols
and phenols with hexamethyldisilazane [8–13], hydrosilanes
[14], disilanes [15], alkylsilanes [16], allylsilanes [17], and
trimethylsilyl azide [18] in the presence of a suitable catalyst.
However, some of these procedures are not adequate for the
chemoselective protection of the hydroxyl group for several
reasons such as low selectivity, long reaction time, low product
yield, toxicity, delicate purification, and lack of reactivity or
difficulty in removing by-products. 1,1,1,3,3,3-Hexame-
thyldisilazane (HMDS) as a cheap, stable, and commercially
available reagent is one of the most widely used silylating
agents for the trimethylsilylation of alcohols and phenols. Its
handling does not require special precautions and the reaction
workup is not time-consuming because the by-product of the
reaction is ammonia, which is simple to remove from the re-
action media. However, the low silylating power of HMDS is
the main drawback for its application. Therefore, to activate
this reagent an appropriate catalyst is required.
1 Experimental
All the chemicals were purchased from Fluka, Merck, or
Aldrich chemical companies. The oxidation products were
characterized by a comparison of their spectral (IR, 1H NMR,
or 13C NMR) and physical data with authentic samples.
–
Phenyltrimethylammonium tribromide (PhMe3N+Br3 ) is a
commercially available material and was purchased from
Merck.
The trimethylsilylation of 2-hydroxy-1,2-diphenylethanone
−
(1j) with HMDS catalyzed by PhMe3N+Br3 as a typical pro-
cedure is outline below. To a mixture of 1j (0.212 g, 1 mmol)
and hexamethyldisilazane (0.323 g, 2 mmol) in CH2Cl2 (10
−
ml), PhMe3N+Br3 (0.018 g, 0.05 mmol) was added and the
mixture was stirred at room temperature for 91 min (reaction
progress monitored by thin layer chromatography). The reac-
Received date: 26 March 2010.
*Corresponding author. Tel: +98-841-2227022; Fax: +98-841-2227022; E-mail: arashghch58@yahoo.com, a.ghorbani@mail.ilam.ac.ir
Foundation item: Supported by the research faculties of Ilam University, Ilam, Iran.
Copyright © 2010, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(10)60107-6

Arash GHORBANI-CHOGHAMARANI et al. / Chinese Journal of Catalysis, 2010, 31: 1103–1106
tion was then quenched with water (10 ml), and the organic
NMR (200 MHz, CDCl3) δ 6.70–6.84 (m, 3H), 3.87 (s, 3H),
2.36 (s, 3H), 0.34 (s, 9H); 13C NMR (50 MHz, CDCl3) δ 150.6,
142.2, 131.4, 121.1, 120.6, 113.1, 55.5, 21.1, 0.6.
Trimethyl(4-benzylphenoxy)silane (2s). 1H NMR (200
MHz, CDCl3) δ 6.95–7.59 (m, 9H), 4.18 (s, 2H), 0.57 (s, 9H);
13C NMR (50 MHz, CDCl3) δ 153.7, 141.7, 134.3, 130.2,
129.1, 128.8, 126.3, 120.2, 41.3, 0.53.
phase was dried over Na2SO4 (3 g) and filtered after 10 min.
Evaporation of dichloromethane gave 1,2-diphenyl-2-
(trimethylsilyloxy)ethanone (0.276 g, 97%) as a white crystal-
line solid; m.p. 119–122 ºC; 1H NMR (90 MHz, CDCl3) δ 8.00
(m, 2H), 7.36–7.51 (m, 8H), 5.92 (s, 1H), 0.15 (s, 9H); IR
(nujol, cm−1): v 1 687, 1 597, 1 578, 1 458, 1 377, 1 251, 1 109,
979, 888, 844, 698.
Trimethyl(phenethoxy)silane (2d). 1H NMR (90 MHz,
CDCl3) δ 7.29 (s, 5H), 3.85 (t, 2H), 2.90 (t, 2H), 0.14 (s, 9H);
IR (KBr, cm−1): v 3 029, 2 956, 1 605, 1 497, 1 454, 1 251,
1 095, 929, 883, 841, 748, 698.
2 Results and discussion
As a continuation of our previous studies on the application
of new reagents and catalysts in organic functional group
transformations [19–26], we now disclose a new, efficient, and
mild procedure for the trimethylsilyl protection of a wide range
of alcohols and phenols using HMDS in the presence of cata-
1
Trimethyl(cholesteroloxy)silane (2k). H NMR (90 MHz,
CDCl3) δ 5.34 (m, 1H), 3.49 (m, 1H), 0.67–2.17 (m, 43H);13C
NMR (25 MHz, CDCl3) δ 141.4, 121.3, 72.4, 56.9, 56.4, 50.4,
42.8, 42.4, 39.9, 39.6, 37.5, 36.6, 36.3, 35.9, 32.0, 28.3, 28.0,
24.4, 24.0, 22.8, 22.6, 21.2, 19.4, 18.8, 11.9, 0.36; IR (nujol,
cm−1): v 2 853, 1 464, 1 456, 1 378, 1 249, 1 085, 896, 840.
–
lytic amounts of PhMe3N+Br3 under mild and homogenous
conditions at room temperature.
Therefore, in this article, we report the efficient trimethyl-
silylation of different types of hydroxyl groups including pri-
mary, secondary, hindered secondary, and substituted phenols
using HMDS (I) in the presence of a catalytic amount of
1
Trimethyl(2-admantanoxy)silane (2l). H NMR (90 MHz,
CDCl3) δ 3.78 (m, 1H), 1.35–2.25 (m, 14H), 0.08 (s, 9H); IR
(nujol, cm−1): v 2 853, 1 450, 1 354, 1 249, 1 133, 1 093, 880,
839, 752.
–
PhMe3N+Br3 (II) in dichloromethane at room temperature
Trimethyl(4-chlorophenoxy)silane (2o). 1H NMR (200
MHz, CDCl3) δ 6.76–7.20 (dd, 71.5, 8.5, Hz, 4H), 0.02 (s, 9H);
13C NMR (50 MHz, CDCl3) δ 156.7, 129.5, 122.8, 117.3, 2.3.
Trimethyl(2-methoxy-4-methylphenoxy)silane (2r). 1H
with good to excellent yields (Scheme 1 and Table 1).
As is evident from Table 1 a good range of turnover number
(TON) and turnover frequency (TOF) for the catalyst is ob-
served. To investigate the role of PhMe3N+Br3– as the catalyst,
H
N
Me3Si
SiMe3
-
Ar–OH or R–OH
Ar–OTMS or R–OTMS
PhMe3N+Br3
1
2
OH
O2N
CH2OH
CH2OH
Cl
CH2OH
CH2CH2OH
1f
CH2OH
O
1b
1a
Cl
1d
1e
1c
OH
OH O
H
H
OH
H3C
CH3
1g
HO
H
H3C
1i
1j
1h
H
H
HO
1k
OH
OH
OH
Cl
OH
MeO
OH
CH2CCH3
CH3
1n
1p
1o
1l
1m
OH
Me
OH
CH2
OH
1q
1s
OMe
1r
Scheme 1. Trimethylsilylation of different types of hydroxyl groups.

Arash GHORBANI-CHOGHAMARANI et al. / Chinese Journal of Catalysis, 2010, 31: 1103–1106
Table 1 Trimethylsilylation of alcohols and phenols (1) to the corresponding trimethylsilyl alcohols and phenols (2) using HMDS (I) in the presence of a
catalytic amount of PhMe3N+Br3− (II) in CH2Cl2 at room temperature
Substrate/HMDS/Cat. (mmol)
Entry
Substrate
Product
Time (min)
Yielda (%)
TON
TOF (min−1)
I
II
1
2
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
0.05
0.07
0.05
0.05
0.05
0.05
0.05
0.05
30
360
180
5
91
90
18.20
12.86
17.80
18.80
19.80
20.00
17.20
18.60
—
0.61
0.04
0.99
3.76
1.98
0.30
0.16
0.93
—
3
89
4
94
5
10
99
100b
6
66
7
1g
1h
1h
1i
2g
2h
2h
2i
105
20
86
8
93
c
d
9
—
1320
60
—
10
11
12
13
14
15
16
17
18
19
20
0.05
0.05
0.07
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
78
97
90
93
—
88
91
90
86
95
98
15.60
19.40
12.86
18.60
—
0.26
0.21
0.09
0.05
—
1j
2j
91
1k
1l
2k
2l
140
360
1200
17
1m
1n
1o
1p
1q
1r
1s
2m
2n
2o
2p
2q
2r
2s
17.60
18.20
18.00
17.20
19.00
19.60
1.04
0.52
1.50
1.72
0.73
0.75
35
12
10
26
26
Reaction conditions: substrate 1 mmol, CH2Cl2 10 ml, room temperature. aIsolated yield. bConversion. cIn the absence of catalyst. dNo reaction.
OH OTMS
OH
OTMS
CH CCH
HMDS (2 mmol)
-
+
CH CCH
2
+
3
2
3
PhMe N+Br (0.05 mmol)
3
3
CH
3
CH
3
CH Cl , rt, 6 h
2
2
100%
0%
OH
OTMS
HMDS (2 mmol)
-
+
+
CH OH
CH OTMS
2
2
PhMe N+Br (0.05 mmol)
3
3
CH Cl , rt, 30 min
2
2
trace
100%
Scheme 2. Comparasion of reactivity of unhindered alcohols and hindered alcohols.
benzhydrol was subjected to the trimethylsilylation reaction in
the absence of a catalyst. However, no product was observed
after 22 h (Table 1, entry 9).
reactive than hindered alcohols and the selectivity is outlined in
Scheme 2.
A plausible mechanism for trimethylsilylation is shown in
Scheme 3. Phenyltrimethylammonium tribromide brominates
hexamethyldisilazane, which polarizes the Si–N bond. The
polarization of the Si–N bond converts HMDS to an activated
silylating agent. Finally, the hydroxyl group silylates and
ammonia is released as a by-product.
Also, our results show that unhindered alcohols are more
Me3SiNHSiMe3
Br
NH
-
3 Conclusions
PhMe3N+Br3
SiMe3
Me3Si
-
PhMe2N.MeBr.Br
We report in this study on a new catalytic method for the
efficient trimethylsilylation of alcohol and phenol derivatives
under metal-free, mild, and homogeneous conditions. This
method offers shorter reaction time, high selectivity, non-toxic
conditions, cost effective reagents and catalyst, and an easy
workup.
R OH
NH3
+
OSiMe3
R
H2
N Br
R
OSiMe3
Me3Si
OH
R
-
PhMe2N.MeBr.Br
Scheme 3. Possible mechanism for trimethylsilylation of alcohols.

Arash GHORBANI-CHOGHAMARANI et al. / Chinese Journal of Catalysis, 2010, 31: 1103–1106
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