Tungstophosphoric acid (H3PW12O40) as a heterogeneous inorganic catalyst. Activation of hexamethyldisilazane (HMDS) by tungstophosphoric acid for efficient and selective solvent-free O-silylation reactions

Article abstract of DOI:10.1039/b208202k

The role of tungstophosphoric acid (H₃PW₁₂O₄₀) as heterogeneous organic catalysts was discussed. Activation of hexamethyldisilazane by tungstophosphoric acid for efficient and selective solvent-free O-silylation reactions

Full text of DOI:10.1039/b208202k

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Tungstophosphoric acid (H3PW12O40) as a heterogeneous
inorganic catalyst. Activation of hexamethyldisilazane (HMDS)
by tungstophosphoric acid for efficient and selective solvent-free
O-silylation reactions
1
Habib Firouzabadi,* Nasser Iranpoor,* Kamal Amani andFarhad Nowrouzi
Department of Chemistry, Shiraz University, Shiraz 71454, Iran.
E-mail: Firouzabadi@chem.susc.ac.ir, Iranpoor@chem.susc.ac.ir; Fax: Int. 711-2280926;
Tel: Int. 711-2284822
Received (in Cambridge, UK) 21st August 2002, Accepted 28th October 2002
First published as an Advance Article on the web 5th November 2002
Tungstophosphoric acid (H3PW12O40) effectively activates
hexamethyldisilazane for the selective silylation of primary,
secondary, tertiary and phenolic hydroxy groups under
solvent-free conditions at 55–60 ЊC.
acid (H3PW12O40) as a reusable and heterogeneous catalyst for
efficient and selective O-trimethylsilylation of a wide variety
of alcohols and phenols using easily available hexamethyl-
disilazane (HMDS) at 55–60 ЊC under solvent-free conditions
(Scheme 1).
Introduction
Uses of heteropolyacids (HPAs) as catalysts for fine organic
synthetic processes have been developed that are very important
for industries related to fine chemicals, such as flavors, pharm-
aceuticals and food industries.1 Heteropolyacids are more active
catalysts than conventional inorganic and organic acids
for various reactions in solution.2 They are used as industrial
catalysts for several liquid-phase reactions,3–6 such as alcohol
dehydration,7 alkylation,8 and esterification9 reactions. Among
heteropolyacids, polytungstic acids are the most widely used
catalysts owing to their high acid strengths, thermal stabilities,
and low reducibilities. Catalysts based on heteropolyacids
have many advantages over liquid acid catalysts. They are
non-corrosive and environmentally benign, presenting fewer
disposal problems. Their repeated use is possible and their sep-
aration from liquid products is easier than for the homogeneous
catalysts.10
We have recently started studies on the catalytic prop-
erties of heteropolyacids, especially tungstophosphoric acid
(H3PW12O40) which is a cheap, reusable, heterogeneous and
easy available catalyst. We have already used this catalyst for
the oxidation of aromatic amines to nitro compounds with
sodium perborate in micellar media, thioacetalization and
transthioacetalization reactions, its caesium salt for regio-
selective bromination of aromatic compounds and oxidation
of hydroxy groups to their corresponding carbonyl functions
with Fe(NO3)3ؒ9H2O activated by H3PW12O40.11
Protection of the hydroxy functional group is an important
process in multi-step synthesis. One of the popular methods for
this purpose is to transfer hydroxy groups of their correspond-
ing silyl ethers. Hexamethyldisilazane (HMDS) is a cheap and
commercially available compound that can be used for the
preparation of trimethylsilyl ethers from hydroxy compounds.
Even though the handling of this reagent is easy, its main
drawback is its poor silylating power which needs forceful
conditions and long reaction times.12 For the activation of
HMDS, a variety of catalysts have been reported.13 Recently
iodine has also been used as an effective catalyst for the
activation of HMDS in silylation reactions.14
Solvent-free reactions have attracted considerable attention
in chemical processes for different reasons. They are valuable
due to environmental safety, the economic viewpoint, easy
work-up, high yields of the products and (usually) their fast
reaction times.15
Scheme 1
Results and discussion
Primarily as a model reaction, silylation of benzyl alcohol with
HMDS was performed in the presence of several heteropoly-
acids and their salts, and some other acids at 55–60 ЊC under
solvent-free conditions (Table 1). In order to show the strong
catalytic activity of heteropolyacids and their salts in com-
parison with other acids, we studied the catalytic activities of
HY-zeolite, Amberlyst-15, triflic acid and sulfuric acid for this
purpose. The results show that in the presence of most of the
heteropolyacids, silylation reactions proceeded efficiently (Table
1, entries 1–6). The results show that tungstophosphoric acid,
H3PW12O40, a commercially available and cheap crystalline
compound, was the most effective catalyst for this purpose and
it was used in 0.01 molar equivalents for the silylation of other
hydroxy compounds throughout this study (Table 1, entry 2).
The observed catalytic activity of H3PW12O40 with Hammett
acidity function Ho < Ϫ13.16 reflects the stronger acidity
strength of this compound in comparison with, for example,
H2SO4 Ho = Ϫ12.16 Recently an acidity scale for Brønsted
acids including H3PW12O40 was reported in the literature.17 The
reported results show the acidity strength follows the order:
H3PW12O40 > p-CH3C6H4SO3H ≈ H2SO4.
We have found that H3PW12O40 is a reusable catalyst and even
after ten runs for the silylation of benzyl alcohol with HMDS,
the catalytic activity of H3PW12O40 was almost the same as that
of the freshly used catalyst. This method can be applied to
liquid or crystalline alcohols and phenols without any
difficulties.
We have applied similar reaction conditions for the silylation
of primary and secondary benzylic alcohols. Reactions pro-
ceeded efficiently with high isolated yields (Table 2, entries 1–7).
Primary and secondary aliphatic alcohols were also converted
to their corresponding silyl ethers under similar reaction con-
ditions with excellent yields (Table 2, entries 8–10). This method
was found to be useful for the protection of hindered secondary
and tertiary alcohols (Table 2, entries 11–15). Phenol, 4-
ClC6H4OH and 4-MeCOC6H4OH were also silylated easily and
their corresponding silyl ethers were isolated in 95%, 85%, and
87% yields respectively (Table 2, entries 16–18). 4-NO2C6H4OH
with a strongly electron-attracting group remained intact under
In continuation of our work on the catalytic properties of
heteropolyacids, herein we report the use of tungstophosphoric
DOI: 10.1039/b208202k
J. Chem. Soc., Perkin Trans. 1, 2002, 2601–2604
This journal is © The Royal Society of Chemistry 2002
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Table 1 Silylation of benzyl alcohol using HMDS in the presence of various heteropolyacids, their salts and some other acids at 55–60 ЊC under
solvent-free conditions
Entry
Catalyst
Substrate : HMDS : catalyst
Time/min
Yield (%)
1
2
3
4
5
6
7
8
9
H3PW12O40
H3PW12O40
H4SiPW12O40
H4PMo12O40ؒnH2O
Ni3(PW12O40)2
Cu3(PW12O40)2
HY Zeolite
Amberlyst-15Hϩ
CF3SO3H
1 : 0.8 : 0.01
1 : 0.8 : 0.01
1 : 0.8 : 0.0075
1 : 0.8 : 0.0075
1 : 0.8 : 0.01
1 : 0.8 : 0.01
1 : 0.8 : 0.1 g
1 : 0.8 : 0.1 g
1 : 0.8 : 0.03
1 : 0.8 : 0.03
1 : 0.8 : 0.015
210
23
40
26
80
100a
100
98
100
90
90
80
60
90
85
120
120
65
35
40
10
11
TsOH
H2SO4
98
96
a The reaction was carried out at room temperature.
Table 2 Silylation of alcohols and phenols using HMDS in the
presence of H3PW12O40 at 55–60 ЊC under solvent-free conditions
functional group was quantitatively protected in the presence
of an amino group [Table 3, eqn. (4)]. The selectivity of the
method in a single molecule carrying primary and secondary
hydroxy groups has also been demonstrated [Table 3, eqn. (5)].
The percentage of the products in the reaction mixture was
determined by GC analysis. The products were separated by
column chromatography using EtOAc–n-hexane (1 : 9) as an
eluent. The major product (5a) was identified by the mild oxid-
ation of the hydroxy group to 4-(trimethylsilyloxy)butan-2-one
(5c). The spectral data of compound 5c are given in the
Experimental section.
In all reactions in this study, generation of ammonia gas
(NH3) from the reaction mixtures can be detected easily. In the
reaction mixtures, H3PW12O40, as a strong acid, reacts with
HMDS to produce [(Me3Si)2NH2]3PW12O40 salt. This salt in
turn reacts with alcohol molecules to produce the correspond-
ing silyl ethers plus an ammonium salt of tungstophosphoric
acid [(NH4)3PW12O40]. In order to study qualitatively the
probable reaction pathway of these reactions, we prepared
highly thermally stable ammonium dodecatungstophosphate
(NH4)3PW12O40 according to the literature procedure.18 Then
the reaction of HMDS molecules with [(NH4)3PW12O40] was
studied. We observed that HMDS reacts immediately with
[(NH4)3PW12O40] to produce ammonia gas plus a greyish white
solid compound. This solid compound as a reagent can easily
convert alcohols to their corresponding silyl ethers. In experi-
ments, we have also studied the reactions of ammonium salt of
dodecatungstophosphoric acid [(NH4)3PW12O40] as a catalyst
with HMDS in the presence of several alcohols. The reactions
proceeded easily with the evolution of ammonia gas and the
production of the corresponding silyl ethers. With this informa-
tion in mind we propose a catalytic reaction cycle in which the
production of [(Me3Si)2NH2]3PW12O40 and [(NH4)3PW12O40] as
catalysts and production of silyl ethers and ammonia gas as the
products of the reactions are clarified (Scheme 2).
Entry
ROH
Time/min
Yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
PhCH2OH
23
7
6
20
16
15
48
18
7
90
82
95
96
93
95
93b
92
96
93
94
90
92
90
96
95
85
87
0
4-ClC6H4CH2OH
4-MeC6H4CH2OH
4-OMeC6H4CH2OH
PhCH(OH)CH3
PhCH(OH)CH2CH3
PhCH(OH)Ph
PhCH2CH2CH2OH
Octan-1-ol
Octan-2-ol
9
tert-Butyl alcohol
Adamantanol
(Ϫ)-Menthol
Norborneol
Terpeneol
PhOH
4-ClC6H4OH
4-MeCOC6H4OH
4-NO2C6H4OH
2-Naphthol
PhNH2
PhCH2SH
PhCOOH
Geraniol
Cinnamyl alcohol
Oct-3-en-1-ol
Hex-3-yne-2,5-diol
30
135
8
30
120
12
3
30
120
6
120
160
180
60
45
55
80
90
0
0
0
c
–
–
–
c
c
c
–
a Isolated yields. b Reaction proceeded more easily in the presence of
1 ml of n-hexane. c Unidentified polymeric material was isolated.
similar reaction conditions (Table 2, entry 19). 2-Naphthol was
also silylated under similar reaction conditions with 90% yield
within 6 min (Table 2, entry 20). Aniline, benzyl thiol and
benzoic acid remained intact in the reaction mixture even after
prolonged reaction times (Table 2, entries 20–22). We found
that this method was not suitable for the protection of allyl and
propargyl alcohols, polymeric materials being produced in their
reaction mixtures (Table 2, entries 24–27).
Selectivity of a method is important in the multi-step prepar-
ation of organic compounds and provides a broad spectrum
for its uses in functional group transformation reactions.
Therefore, we tried several competitive reactions under similar
conditions in order to show the scope and limitation of this
catalytic system. By this system, a primary benzylic hydroxy
group can be protected in the presence of a secondary aliphatic
alcohol with the ratio of 80 : 20 [Table 3, eqn. (1)]. A secondary
aliphatic alcohol was protected in the presence of a secondary
benzylic alcohol with the ratio of 80 : 20 [Table 3, eqn. (2)]. A
secondary aliphatic alcohol in the presence of a tertiary alcohol
was protected with the ratio of 95 : 5 [Table 3, eqn. (3)].
Reaction of 3-aminophenol was also studied to investigate the
selectivity of the method. It was observed that the phenolic
Scheme 2
In conclusion, in this study we have introduced a new
catalytic application of tungstophosphoric acid H3PW12O40 as
the activator of HMDS for the efficient protection of a variety
of alcohols and phenols under solvent-free conditions.
By this method, bulky secondary and tertiary hydroxy func-
tional groups were protected efficiently with excellent yields.
2602
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Table 3 Competitive silylation reactions of alcohols using HMDS in the presence of H3PW12O40 at 55–60 ЊC under solvent-free conditions
The method shows reasonably high selectivity among different
hydroxy and amine functional groups. The catalyst is a hetero-
geneous, recyclable, non-corrosive and environmentally benign
compound. Isolation of the product from a heterogeneous
reaction mixture is much easier than from a homogeneous
system and by a simple extraction and evaporation of the
solvent, the pure product could be isolated. The catalytic
activity of H3PW12O40 was found to be much higher than that
of HY-zeolite, Amberlyst-15, triflic acid, toluene-p-sulfonic
acid and sulfuric acid.
CH2–OTMS), 0.06 [s, 9H, –OSi(CH3)3]; IR (KBr): 3442 (OH),
1251 (OTMS) cmϪ1.
5c: 1H NMR (250 MHz, CDCl3): δ = 0.06 [s, 9H, OSi(CH3)3],
3.47 (t, 2H, CH2–OTMS), 2.48 (t, 2H, CH2–CO), 2.25 (s, 3H,
CH3–CO); IR (KBr): absence of OH absorption, 1643 (CO),
1251 (OTMS) cmϪ1.
Acknowledgements
The authors are grateful to the generous support of this work
by the Shiraz University Research Council.
Experimental
References
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General procedure for silylation of alcohols using HMDS
catalyzed with tungstophosphoric acid
Alcohol (1 mmol), HMDS (0.8 mmol) and the catalyst
(0.01 mmol, 0.028 g) were mixed and heated at 55–60 ЊC for
the appropriate reaction time (Table 2). After completion of
the reaction (monitored by TLC and GC), n-hexane (5 ml) was
added and the catalyst was recovered by filtration and was
washed with n-hexane (2 × 5 ml). The filtrate was then washed
with water (10 ml) to destroy the extra amounts of
HMDS and the organic layer was dried over anhydrous
Na2SO4. Evaporation of the solvent under reduced pressure
gave the highly pure product without further purification.
1
4a: H NMR (250 MHz, CDCl3): δ = 3.58 [s, 2H (NH2)],
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3478, 1600, N–H, 1253 (O–TMS) cmϪ1.
5a: 1H NMR (250 MHz, CDCl3): δ = 1.09 (d, 3H,
CH3–CHOH), 3.45–3.58 (m, 1H, –CH–OH), 3.8 (s, 1H, –OH),
1.32–1.66 (m, 2H, CH3CH(OH)–CH2–CH2–OTMS), 3.6 (t, 2H,
J. Chem. Soc., Perkin Trans. 1, 2002, 2601–2604
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