Silica sulfate, an efficient catalyst for the trimethylsilylation of alcohols

Article abstract of DOI:10.1080/00397910600602495

An easy method for the preparation of trimethylsilyl ethers from alcohols and 1,1,1,3,3,3-hexamethyl-disilazane (HMDS) using silica sulfate as a catalyst under mild conditions in excellent yields is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600602495

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Silica Sulfate, an Efficient Catalyst for the
Trimethylsilylation of Alcohols
Tong‐Shou Jin a , Ruo‐Fei Tian a , Li‐Bin Liu a , Ying Zhao a & Tong‐Shuang Li a
a Department of Chemistry, College of Chemistry and Environmental
Science , Hebei University , Baoding, China
Published online: 18 Aug 2006.
To cite this article: Tong‐Shou Jin , Ruo‐Fei Tian , Li‐Bin Liu , Ying Zhao & Tong‐Shuang Li (2006) Silica
Sulfate, an Efficient Catalyst for the Trimethylsilylation of Alcohols, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:13, 1823-1828, DOI:
10.1080/00397910600602495
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Synthetic Communicationsw, 36: 1823–1828, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600602495
Silica Sulfate, an Efficient Catalyst
for the Trimethylsilylation of Alcohols
Tong-Shou Jin, Ruo-Fei Tian, Li-Bin Liu, Ying Zhao,
and Tong-Shuang Li
Department of Chemistry, College of Chemistry and Environmental
Science, Hebei University, Baoding, China
Abstract: An easy method for the preparation of trimethylsilyl ethers from alcohols
and 1,1,1,3,3,3-hexamethyl-disilazane (HMDS) using silica sulfate as a catalyst
under mild conditions in excellent yields is described.
Keywords: Alcohols, hexamethyldisilazane, protection, silica sulfate, trimethylsilyl
ethers
INTRODUCTION
Selective protection and deprotection of hydroxyl groups by the formation of
silyl ethers is of great importance in organic synthesis.[1] Silyl ethers are easy
to prepare, are resistant to oxidation, have good heat stability, have low
viscosity, and allow their parent compounds to be recovered easily.[2]
1,1,1,3,3,3-Hexamethyl-disilazane (HMDS) has been found to be a con-
venient reagent for converting alcohols to their trimethylsilyl derivates.[2–7]
HMDS is a cheap and commercially available reagent, giving ammonia as the
only by-product, and the products are separated from an excess of HMDS by
a simple distillation. The main drawback of this reagent is its poor silylating
power, which needs forceful conditions in many instances and reactions.
The activity of HMDS has been increased drastically by using some
catalysts. Sulfuric acid,[1] chlorotrimethylsilane,[2] montmorillonite K-10,[3]
Received in Japan October 23, 2005
Address correspondence to Tong-Shou Jin, Department of Chemistry, College of
Chemistry and Environmental Science, Hebei University, No. 88 Hezuo Road,
Baoding 071002, China. E-mail: orgsyn@mail.hbu.edu.cn
1823

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T.-S. Jin et al.
zinc chloride,[8] and phosphomolybdic acid[9] as catalysts are employed for the
preparation of trimethylsilyl ethers. These catalysts have their advantages,
but they also have some disadvantages. For example, silylation of alcohols
using a conventional strong acid as catalyst is not suitable, because of usually
accompanying side reaction such as etherification, oxidation, elimination, and
carbonization; tedious workup; problems of corrosivity, pollution, and nonrecov-
erability of catalyst; and long reaction time. Consequently, there is a genuine
need for efficient and heterogeneous catalytic methods for this reaction using
an inexpensive, nonpolluting, and easily handled catalyst.
Silica sulfate, a new type of solid acid, has been studied recently.[10–17] It
has many advantages, such as high reactivity and nontoxicity. Silica sulfate is
superior to the other reported acidic solid supports or acidic resins, such as
polysyrene sulfonic acid and Nafion-H, for running reactions under hetero-
geneous conditions. Therefore, we are interested in using this inorganic
acidic resin as a solid acid. Herein we demonstrated a rapid and efficient
method for silylation of a series of alcohols with HMDS catalyzed by silica
sulfate solid acid at room temperature or at refluxing temperature (Scheme 1).
RESULTS AND DISCUSSION
In the presence of silica sulfate, treatment of a variety of alcohols 1 with
HMDS 2 in dichloromethane or chloroform (except for those in absence of
solvent) at mild temperature gave the corresponding trimethylsilyl ethers 3
in good to excellent yields. The results are shown in Table 1.
The present procedure for preparation of trimethylsilyl ethers is quite
general, as a wide range of hydroxy-containing compounds such as primary
alcohols (1a, 1b, 1f, 1g, 1h, 1i, 1l, and 1m) and secondary alcohols (1c, 1e,
1j, and 1n) were protected in excellent yields.
We found that treatment of Betulin 1o with different equivalents of
HMDS gave different amounts of mono- and disilylated products. For
example, it only afforded 3o in 8% yield and 4o in 36% yield when 1 equiv-
alent of HMDS in chloroform refluxing for 50 min in presence of silica sulfate
was used, whereas by employing 1.5 equivalent of HMDS, it gave 3o in 92%
yield and 4o in 10% yield under the same conditions (Scheme 2).
It is noteworthy that tertiary alcohols showed the lowest activity, although
they were silylated with HMDS in the presence of silica sulfate at higher temp-
erature and longer reaction time, only a little of products 3 was obtained. For
example, triphenylmethanol 1k required a longer reaction time (5 h) and
Scheme 1.

Silica Sulfate
1825
Table 1. Silylation of alcohols by using HMDS in presence of silica sulfate
Reaction
temp
Reaction
time min (h)
Yield
(%)a
Entry
Alcohols
Solvent
1
2
n-Butyl alcohol (1a)
iso-Butyl alcohol (1b)
sec-Butyl alcohol (1c)
tert-Butyl alcohol (1d)
Cyclohexanol (1e)
None
None
None
None
None
None
None
CHCl3
None
CH2Cl2
CHCl3
r.t.
r.t.
10
12
(1)
(3)
25
15
14
15
10
30
(5)
35
30
(1)
50
30
50
96
95
86
80
84
94
95
92
93
86
67
94
92
88
92b
92
84
3
r.t.
4
Reflux
r.t.
r.t.
5
6
n-Decanol (1f)
7
n-Octyl alcohol (1g)
Octadecyl alcohol (1h)
Benzyl alcohol (1i)
Benzhydrol (1j)
r.t.
r.t.
8
9
r.t.
r.t.
10
11
12
13
14
15
16
17
Triphenylmethanol (1k)
Reflux
r.t.
r.t.
Phenoxy ethyl alcohol (1l) None
2-Phenylethanol (1m)
Benzoin (1n)
Betulin (1o)
CH2Cl2
CH2Cl2
CHCl3
CHCl3
CH2Cl2
Reflux
Reflux
Reflux
r.t.
Cholesterol (1p)
b-Sitosterol (1q)
aYields refer to isolated products.
bYield refer to disilylated product.
higher temperature (reflux) and gave product 3k with a little lower yield
(67%). Therefore, primary alcohols could be protected more easily than
secondary alcohols, and secondary alcohols could be protected more easily
than tertiary alcohols.
The catalyst was easily regenerated by washing with ethanol, followed by
drying at room temperature for 4 h. The catalyst could be reused six times for
the synthesis of 3a without significant loss of activity.
We have developed preparative procedures for trimethylsilyl ethers with
the advantages of operational simplicity, high yields, short reaction times, and
recyclable and environmentally friendly catalyst.
Scheme 2.

1826
T.-S. Jin et al.
EXPERIMENTAL
Products were characterized by their melting points, spectral characteristics
1
(IR and H NMR), and comparison with authentic samples. IR spectra were
1
recorded on a Bio-Rad FTS-40 spectrometer (KBr). H NMR spectra were
determined in D-chloroform solution on a FT-NMR Bruker 300 (300 MHz)
and reported in d ppm using tetramethylsilane as the standard.
Preparation of Silica Sulfate[18]
A 500 mL suction flask was used. It was equipped with a constant-pressure
dropping funnel containing chlorosulfonic acid (58.3 g, 0.5 mol) and gas inlet
tube for conducting HCl gas over an absorbing solution. It was charged with
silica gel (100 g) and CH2Cl2 (50 mL). Chlorosulfonic acid was added
dropwise over a period of 30 min under stirring at room temperature. HCl
gas evolved from the reaction vessel immediately. After the addition was
completed, the mixture was shaken for 30 min. Evaporation of the solvent
CH2Cl2 and HCl occurred under reduced pressure. A white solid (silica
sulfate) (120.0 g, ꢀ100%) was obtained and stored in an adesiccator until use.
General Procedure for Silylation of Alcohols by using HMDS
in Presence of Silica Sulfate
A mixture of alcohol (3 mmol) and HMDS (2.0 mmol) in dry dichloromethane
or chloroform (5 mL) (except for those in absence of solvent) was stirred in
the presence of silica sulfate (100 mg) at room or refluxing temperature for
the length of time as indication in Table 1. The reaction was monitored by
TLC. After completion of the reaction, mixture was filtered, and catalyst
was washed with dichloromethane or chloroform (2 ꢀ 5 mL). Removal of
the solvent under reduced pressure afforded the crude product. The crude
product was purified by distillation or column chromatograph on silica gel
with a mixture of petroleum ether and diethyl ether as eluent to give trimethyl-
silyl ethers 3.
Data of Some Compounds
3f. N25 1.4206; IR (KBr): nmax 2960, 2860, 1460, 1380, 1254, 1102, 874, 842,
730 cm 21; 1H NMR (CDCl3): dH 3.55 (2H, t, J ¼ 6.2 Hz, OCH2), 1.28 (16H,
brs, 8CH2), 0.88 (3H, t, J ¼ 6.4 Hz, CH3), 0.10 (9H, s, SiMe3).
3o. Mp 127–1298C (colorless platelets from cyclohexane); IR (KBr): nmax
3066, 2960, 2880, 1640, 1458, 1376, 1260, 1088, 886, 842, 750 cm21
;

Silica Sulfate
1827
1H NMR (CDCl3): dH 4.68 (1H, brs, 29-H), 4.58 (1H, brs, 29-H0), 3.68 (1H, d,
J ¼ 9.8 Hz, 28-H), 3.24 (1H, d, J ¼ 9.8 Hz, 28-H0), 3.16 (1H, m, 3-H), 2.06–
1.02 (complex, CH2, CH), 1.68 (3H, s, 30-Me), 1.02, 0.98, 0.88, 0.86, 0.78
(15H, all s, 5Me), 0.10 (18H, s, 2 ꢀ SiMe3).
3p. Mp 128–1298C (colorless needles from cyclohexane); IR (KBr): nmax
2960, 2876, 1464, 1380, 1258, 1100, 902, 842, 756 cm21
;
1H NMR
(CDCl3): dH 5.34 (1H, d, J ¼ 4.4 Hz, 6-H), 3.50 (1H, m, 3a-H), 1.16 (3H,
s, 19-Me), 0.98 (3H, d, J ¼ 6.2 Hz, 21-Me), 0.88 (6H, d, J ¼ 6.6 Hz, 26, 27-
Me), 0.70 (3H, s, 18-Me), 0.12 (9H, s, SiMe3).
3q. Mp 88–908C (colorless platelets from cyclohexane); IR (KBr): nmax 2960,
1
1460, 1378, 1250, 1100, 900, 750 cm21; H NMR (CDCl3): dH 5.32 (1H, d,
J ¼ 4.2 Hz, 6-H), 3.48 (1H, m, 3a-H), 1.08 (3H, s, 19-Me), 0.68 (3H, s, 18-
Me), 0.12 (9H, s, SiMe3).
4o. Mp 121–1228C (colorless platelets from cyclohexane); IR (KBr): nmax
3358, 3075, 2958, 1640, 1456, 1372, 1252, 1096, 1040, 882, 840,
;
740 cm21 1H NMR (CDCl3): dH 4.67 (1H, brs, 29-H), 4.58 (1H, brs,
29-H0), 3.67 (1H, d, J ¼ 9.7 Hz, 28-H), 3.23 (1H, d, J ¼ 9.7 Hz, 28-H0),
3.17 (1H, m, 3-H), 2.05–1.04 (complex, CH2, CH), 1.69 (3H, s, 30-H), 1.04
(3H, s, Me), 0.98 (3H, s, 2 ꢀ Me), 0.84 (3H, s, Me), 0.76 (3H, s, Me), 0.11
(9H, s, SiMe3).
ACKNOWLEDGMENTS
The project was supported by National Natural Science Foundation of China
(29872011), Educational Ministry of China, Educational Department of Hebei
Province (990104), and Science and Technology Commission of Hebei
Province.
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