Al(HSO4)3 as an efficient reagent for the selective trimethylsilylation of primary alcohols under solvent-free conditions

Article abstract of DOI:10.1080/104265090920930

Primary alcohols are selectively trimethylsilylated using Hexamethyldisilazane (HMDS) in the presence of a catalytic amount of Al(HSO ₄)₃ under solvent free conditions. Copyright Taylor & Francis Inc.

Full text of DOI:10.1080/104265090920930

Phosphorus, Sulfur, and Silicon, 180:2299–2302, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090920930
Al(HSO4)3 as an Efficient Reagent for the Selective
Trimethylsilylation of Primary Alcohols Under
Solvent-Free Conditions
Farhad Shirini
Department of Chemistry, College of Science, Guilan University,
Rasht, Iran
Mohammad Ali Zolfigol
Department of Chemistry, College of Science, Bu-Ali Sina University,
Hamadan, Iran
Masoumeh Abedini
Department of Chemistry, College of Science, Guilan University,
Rasht, Iran
Primary alcohols are selectively trimethylsilylated using Hexamethyldisilazane
(HMDS) in the presence of a catalytic amount of Al(HSO ) under solvent free
4 3
conditions.
Keywords Alcohols; Al(HSO4)3; hexamethyldisilazane (HMDS); solvent-free conditions;
trimethylsilylation
Trimethylsilylation is one of the important methods that is used for
the protection of the hydroxyl group.1 A large number of reagents and
methods have been reported for this purpose, such as allylsilanes,2,3
chlorotrimethylsilane/lithium disulfate,4 hexamethyldisiloxane,5 and
N-trimethyl-2-oxazolidinone.6
Hexamethyldisilazane (HMDS) is a stable, commercially avail-
able, and cheap reagent for trimethylsilylation of hydrogen-labile
substrates,1 giving ammonia as the only byproduct. On the other hand,
silylation using this reagent is nearly neutral and does not need spe-
cial precautions. However, the low-silylating power of HMDS is a main
drawback for its application, which needs forceful conditions and long
Received October 12, 2004; accepted October 14, 2004.
We are thankful to the Guilan University Research Council for the partial support of
this work.
Address correspondence to Farhad Shirini, Guilan University, Department of Chem-
istry, College of Science, Rasht 41335, Iran. E-mail: shirini@guilan.ac.ir
2299

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F. Shirini et al.
reaction times in many instances. A variety of catalysts such as zir-
conium sulfophenyl phosphonate,7 K-10 montmorilonite,8 Me3SiCl,9
sulfonic acids,10 and nitrogen ligand complexes of methachlorides11
have been reported for the activation of HMDS.
Solvent-free reactions have attracted considerable attention in chem-
ical processes for different reasons. They are valuable due to environ-
mental safety, the economic viewpoint, easy work up, high yields of the
products, and (usually) their fast reactions.12
In continuation of our studies on the applications of Al(HSO4)3,13−16
herein we wish to report a mild and efficient method for the trimethylsi-
lylation of primary alcohols using HMDS in the presence of a catalytic
amount of this reagent (Scheme 1). All reactions were performed at
80◦C under solvent-free conditions in good to high yields.
HMDS,Al(HSO4)3
RCH2OH −−−−−−−−−−−→ RCH2OSiMe3
Solvent free,80◦C
SCHEME 1
As shown in Table I, trimethylsilylation of the secondary and ter-
tiary alcohols using this method is very slow (Table I, entries 12–15).
Therefore, this methodology can be used for the selective silylation be-
tween primary and secondary or tertiary alcohols. This is exemplified
by the competitive reaction between 4-chlorobenzylalcohol and triph-
enylmethanol (Table I, entry 16).
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 II).17,18
The mildness of the reaction conditions, high efficiency, selectivity,
reasonable yields of products, a simple and clean work up, and solvent-
free reaction conditions are among the advantages of this new method.
EXPERIMENTAL
General
Chemicals were purchased from Fluka, Merck, and Aldrich. Products
were separated and purified by different chromatographic techniques
and were identified by the comparison of their m.p., IR, NMR, and re-
fractive index with those reported for the authentic samples. All yields
refer to the isolated products. The purity determination of the sub-
strates and reaction monitoring were accompanied by TLC on silica gel
polygram SILG/UV 254 plates. Column chromatography was carried
out on Merck kisselgel 60H.

Selectively Trimethylsilylated Primary Alcohols
2301
TABLE I Selective Trimethylsilylation of Alcohols Under
Solvent-Free Conditionsa
Entry
Substrate
Product
Time (h)
Yield %b
1
2
3
4
5
6
7
8
9
2-ClC6H4CH2OH
4-ClC6H4CH2OH
2-BrC6H4CH2OH
4-Me3CC6H4CH2OH
2-MeC6H4CH2OH
2-O2NC6H4CH2OH
4-O2NC6H4CH2OH
PhCH2CH2OH
PhCH(Me)CH2OH
PhCH2CH2CH2OH
PhCH=CHCH2OH
Ph2CHOH
2-ClC6H4CH2OTMS
4-ClC6H4CH2OTMS
2-BrC6H4CH2OTMS
4-Me3CC6H4CH2OTMS
2-MeC6H4CH2OTMS
2-O2NC6H4CH2OTMS
4-O2NC6H4CH2OTMS
PhCH2CH2OTMS
PhCH(Me)CH2OTMS
PhCH2CH2CH2OTMS
PhCH=CHCH2OTMS
Ph2CHOTMS
0.42
0.08
0.42
0.33
0.25
0.75
0.33
0.42
1.12
0.33
0.33
4
92
90
90
90
95
92
90
90
80
85
90
50
10
11
12
13
4
50
14
2.5
50
15
16
Ph3COH
4-ClC6H4CH2OH
+
Ph3CHOTMS
4-ClC6H4CH2OTMS
+
4.5
5
85c
+
0.08
Ph3COH
Ph3CHOTMS
0c
aProducts were identified spectroscopically and also by the conversion of the products
to their corresponding alcohols.
bIsolated yield.
cGC yield.
General Procedure for Trimethylsilylation of Primary Alcohols
Under Solvent-Free Conditions
HMDS (0.75 mmol), alcohol (1 mmol) and Al(HSO4)3 (0.06 mmol, 0.02
g) were mixed and heated in an oil bath (80◦C) for the specified time
(Table I). After completion of the reaction (monitored by TLC or GC),
TABLE II Comparison of Some of the Results That Were Obtained
by the Silylation of Alcohols with HMDS in the Presence of
Al(HSO4)3(1), With Some of Those reported by LiClO4 (2),17 and
Silica Chloride (3)18
(min) (Yield %) (Substrate: HMDS: Catalyst)
Entry
Substrate
1
2
3
1
2
3
2-Methylbenzyl alcohol
4-Chlorobenzyl alcohol
Cinnamyl alcohol
(15) (95)
(4.8) (92)
(20) (90)
—
(36) (90)
(30) (92)
(18) (70)
(1.8) (67)
(1) (70)

2302
F. Shirini et al.
n-hexane (5 mL) was added and then filtered. The solid residue was
washed with n-hexane (20 mL). The filtrate was then washed with wa-
ter (10 mL) to destroy the extra amounts of HMDS and the organic
layer was dried over anhydrous MgSO4. Evaporation of the solvent gave
the highly pure product. Further purification proceeded by bulb-to-bulb
distillation under reduced pressure, vacuum distillation, or recrystal-
lization to afford pure silyl ether.
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