Silylation and tetrahydropyranylation of alcohols catalyzed by Al(HSO 4)3

Article abstract of DOI:10.1246/bcsj.78.1982

Trimethylsilylation and tetrahydropyranylation of alcohols are efficiently catalyzed by Al(HSO₄)₃. All reactions were performed under mild and completely heterogeneous conditions in good-to-high yields.

Full text of DOI:10.1246/bcsj.78.1982

1982 Bull. Chem. Soc. Jpn., 78, 1982–1985 (2005)
Ó 2005 The Chemical Society of Japan
Silylation and Tetrahydropyranylation of Alcohols
Catalyzed by Al(HSO4)3
ꢀ
Farhad Shirini, Mohammad Ali Zolfigol,1 and Masoumeh Abedini
Department of Chemistry, College of Science, Guilan University, Rasht 41335, Iran
1Department of Chemistry, College of Science, Bu-Ali Sina University, Hamadan 65174, Iran
Received April 5, 2004; E-mail: shirini@guilan.ac.ir
Trimethylsilylation and tetrahydropyranylation of alcohols are efficiently catalyzed by Al(HSO4)3. All reactions
were performed under mild and completely heterogeneous conditions in good-to-high yields.
The hydroxy group is present in a number of compounds of
biological and synthetic interest. Protection of this functional
Al(HSO4)3
ROH
ROR′
group during a multi-step synthesis is an important process,
which is under considerable attention of organic chemists.1
The conversion hydroxy groups to their corresponding tri-
methylsilyl and tetrahydropyranyl ethers is one of the popular
methods used for this purpose. 1,1,1,3,3,3-Hexamethyldi-
silazane (HMDS) as a cheap and commercially available
material is one of the reagents that is used for the silylation
of alcohols.2,3 It’s handling does not need special precaution,
and work-up of the reaction mixture is not time consuming.
However, the low silylating power of HMDS is a main draw-
back for its application, which needs forceful conditions and
long reaction time in a many instances.4 For the activation
of HMDS, a variety of catalysts, such as Me3SiCl,5 zirconium
sulfophenylphosphonate,6 K-10 montmorillonite,7 and silicon
chloride,8 have been reported.
n-hexane
Scheme 1.
R′= SiMe3, THP
native method, especially using heterogeneous catalysts for the
protection of alcohols as THP ethers.
In recent years, we were interested to develop the applica-
tion of hydrogensulfate salts in organic chemistry.24–26 In con-
tinuation of these studies, herein, we wish to report an efficient
method for the trimethylsilylation and tetrahydropyranyl-
ation of alcohols in the presence of a catalytic amounts of
Al(HSO4)3,27,28 under mild and completely heterogeneous
reaction conditions (Scheme 1).
Different types of benzylic alcohols having both electron-
withdrawing and -donating groups were trimethylsilylated
with HMDS in the presence of a catalytic amounts of
Al(HSO4)3 in n-hexane under reflux conditions in good-to-
high yields (Table 1, Entries 1–7). Primary and secondary ali-
phatic alcohols were also efficiently converted to their corre-
sponding trimethylsilyl ethers under the same reaction condi-
tions (Table 1, Entries 8–10). This method was found to be
useful for the protection of hindered secondary and tertiary
alcohols (Table 1, Entries 11–14). This method is also useful
for the silylation of allylic alcohols (Table 1, Entry 15).
The mechanism of the reaction is not clear, but the fast evo-
lution of NH3 gas from the reaction mixture and the reusability
of the catalyst for three times without any considerable loss of
activity, directed us to accept the mechanism that is shown in
Scheme 2 as a most probable one.
Although, using these reagents causes a considerable en-
hancement in the activity of HMDS, in most cases the reaction
with hindered alcohols do not take place,5 or requires forceful
conditions and prolonged reaction times.4
Because of the remarkable stability of tetrahydropyranyl
ethers towards a variety of conditions, such as strongly basic
media, Grignard reagents and alkyllithiums, reduction with hy-
dride, oxidation, oxidative alkylation, and acylation reactions,9
tetrahydropyranylation has found a wide variety of applica-
tions in protecting the hydroxy group of alcohols. A variety
of reagents have been developed for the tetrahydropyranyla-
tion of hydroxy functions, which include mainly protic acids,10
Lewis acids,11 ion exchange resins (Amberlyst H1512 and
Nafion-H13), I2,14 CuCl2,15 zinc chloride on alumina,16 2,3-
dichloro-5,6-dicyano-p-benzoquinone (DDQ),17 lithium tri-
flate,18 calcium chloride,19 sulfuric acid on silica gel,20 dialkyl-
imidazolium tetrachloroaluminates,21 bis(trimethylsilyl sul-
fate),22 and H-Y zeolite.23 Although these methods are satis-
factory for many molecules, some have limitations, such as
the use of strongly acidic media, expensive reagents, tedious
and time-consuming work-up procedures, refluxing conditions,
high catalyst to substrate ratio, long reaction times, the forma-
tion of polymeric byproducts of the dihydropyran, and isomer-
ization. Thus, there is still a need for a mild and efficient alter-
In order to show the efficiency of this method, we have
compared some of the results with some of those reported in
the literature (Table 2).8,29
The tetrahydropyranylation of alcohols with DHP was per-
formed in the presence of catalytic amounts of Al(HSO4)3 in
n-hexane at room temperature and under completely heteroge-
neous reaction conditions, to produce the desired tetrahydro-
pyranyl ether in good-to-high yields (Table 3). Benzylic, allyl-
ic, primary, and secondary alcohols were protected without the
Published on the web October 31, 2005; DOI 10.1246/bcsj.78.1982

F. Shirini et al.
Bull. Chem. Soc. Jpn., 78, No. 11 (2005) 1983
aÞ
Table 1. Silylation of Alcohols Using HMDS in the Presence of Al(HSO4)3
Entry
Substrate
HMDS:Al(HSO4)3
Time/h
Yield/%bÞ
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
2-Chlorobenzyl alcohol
4-Chlorobenzyl alcohol
2-Bromobenzyl alcohol
2-Methylbenzyl alcohol
2-Nitrobenzyl alcohol
4-tert-Butylbenzyl alcohol
2-Phenylethanol
0.6:0.04
0.6:0.04
0.6:0.04
0.6:0.04
0.75:0.06
0.6:0.04
0.6:0.04
0.75:0.06
0.6:0.04
0.6:0.04
0.75:0.06
0.75:0.06
0.75:0.06
0.75:0.06
0.75:0.06
1
90
92
85
90
78
80
90
91
89
80
95
90
85
80
70
0.67
1.5
0.83
4
0.42
1.5
0.42
0.83
0.5
1
3-Phenyl-1-propanol
2-Phenyl-1-propanol
1-Phenyl-2-propanol
(ꢁ)-Menthol
1-Adamantanol
4
4
4
1.7
2-Adamantanol
Cholesterol
Cinnamyl alcohol
a) Products were identified spectroscopically and also by the conversion of the products to their
corresponding alcohols. b) Isolated yields.
2ROH
2ROSiMe
3
Al(HSO )
-
+
+
-
4 3
[(Me Si) N ]Al(HSO )
(Me Si) NH
H N Al(HSO )
3
2
4 3
3
2
3
4 3
H
NH
(Me Si) NH
3 2
3
Scheme 2.
Table 2. Comparison of Some of the Results Obtained by Silylation of Alcohols with HMDS in the
Presence of Al(HSO4)3 (1), with Some of Those Reported by LiClO4 (2)29 and Silicon Chloride (3)8
Entry
Substrate
(Time/min)(Yield/%)(Substrate:HMDS:Catalyst)
1
2
3
1
2
(ꢁ)-Menthol
(60)(95)(1:0.75:0.06)
(40)(92)(1:0.6:0.04)
(3)(76)(1:0.5:0.1)
(1.8)(67)(1:0.5:0.1)
—
(30)(92)(1:1:0.05)
4-Chlorobenzyl alcohol
formation of any other side products in the presence of 0.035
mol equiv of the catalyst. Tertiary alcohols gave poor yields
under the same reaction conditions (Table 3, Entry 17). We
then investigated the possibility for the selective tetrahydro-
pyranylation of the above-mentioned alcohols in the presence
of the tertiary ones. This is exemplified by the competitive
reaction between benzyl alcohol and 1-adamantanol (Table 3,
Entry 18).
To illustrate the efficiency of the proposed method, Table 4
compares some of our results with some of those reported by
the relevant reagents in the literature.18,30
In conclusion, in this study, we developed a simple, mild,
and efficient procedure for the conversion of alcohols to their
corresponding trimethylsilyl and tetrahydropyranyl ethers. In
addition, the availability of the reagent, short reaction times,
high yields of the products, easy work-up, and heterogeneous
reaction conditions are other advantages of the present method,
which make this procedure a useful and attractive addition to
the currently available methods.
Experimental
Chemicals were purchased from Fluka, Merck, and Aldrich
Chemical Companies. All of the trimethylsilyl and tetrahydro-
pyranyl ethers are known compounds, and were characterized
by spectral analyses, comparisons with authentic samples (IR
and NMR), and also by regeneration of the corresponding alco-
hols. All yields refer to the isolated products. The purity determi-
nation of the substrate and reaction monitoring were accompanied
by TLC on silica-gel polygram SILG/UV 254 plates.
General Procedure for Silylation of Alcohols. To a mixture
of the substrate (10 mmol) and Al(HSO4)3 (0.4–0.6 mmol) in hex-
ane (30 mL), HMDS (6–7.5 mmol) was added dropwise within 5

1984 Bull. Chem. Soc. Jpn., 78, No. 11 (2005)
Protection of Alcohols Catalyzed by Al(HSO4)3
aÞ
Table 3. Tetrahydropyranylation of Alcohols in the Presence of Al(HSO4)3
Entry
Substrate
Product
Time/h
Yield/%bÞ
1
2
3
4
5
6
7
8
9
10
11
12
13
C6H5CH2OH
4-ClC6H4CH2OH
2-ClC6H4CH2OH
C6H5CH2OTHP
4-ClC6H4CH2OTHP
2-ClC6H4CH2OTHP
0.17
0.33
0.27
0.25
0.25
3
0.5
0.92
4
0.33
0.5
0.25
0.5
92
90
95
95
90
70
85
92
65
90
85
95
85
2-BrC6H4CH2OH
2-BrC6H4CH2OTHP
2-MeC6H4CH2OH
4-PhCH2OC6H4CH2OH
4-Me3CC6H4CH2OH
C6H5CH(OH)C6H5
C6H5CH(OH)COC6H5
C6H5CH2CH2OH
C6H5CH2CH2CH2OH
C6H5CH(CH3)CH2OH
C6H5CH2CH(OH)CH3
2-MeC6H4CH2OTHP
4-PhCH2OC6H4CH2OTHP
4-Me3CC6H4CH2OTHP
C6H5CH(OTHP)C6H5
C6H5CH(OTHP)COC6H5
C6H5CH2CH2OTHP
C6H5CH2CH2CH2OTHP
C6H5CH(CH3)CH2OTHP
C6H5CH2CH(OTHP)CH3
OH
OTHP
14
1.5
90
H
H
15
3
90
H
H
H
H
HO
THPO
16
17
PhCH=CHCH2OH
PhCH=CHCH2OTHP
0.33
1
75
10
OH
OTHP
C6H5CH2OH
+
C6H5CH2OTHP
+
100cÞ
+
TracecÞ
18
0.17
OH
OTHP
a) Products were identified spectroscopically and also by the conversion of the products to their
corresponding alcohols. b) Isolated yields. c) GC yield.
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