Simple and practical protocol for the silylation of phenol derivatives using reusable NaHSO4 dispread on silica gel under neutral conditions

Article abstract of DOI:10.1080/10426500600892487

A simple and mild procedure for the trimethylsilylation of a wide variety of phenols with hexamethyldisilazane (HMDS) on the surface of silica gel dispersed with NaHSO₄ at r.t. in a few minutes with excellent yields under neutral conditions is

Full text of DOI:10.1080/10426500600892487

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Simple and Practical Protocol
for the Silylation of Phenol
Derivatives Using Reusable
NaHSO4 Dispread on Silica Gel
Under Neutral Conditions
Mahideh S. Khalili a , Hossein Ghafuri a , Samaneh
Mojahedi-Jahromi a & Mohammed M. Hashemi a
a Department of Chemistry , Sharif University of
Technology , Tehran, Iran
Published online: 01 Feb 2007.
To cite this article: Mahideh S. Khalili , Hossein Ghafuri , Samaneh Mojahedi-Jahromi
& Mohammed M. Hashemi (2007) Simple and Practical Protocol for the Silylation
of Phenol Derivatives Using Reusable NaHSO4 Dispread on Silica Gel Under Neutral
Conditions, Phosphorus, Sulfur, and Silicon and the Related Elements, 182:1, 175-179,
DOI: 10.1080/10426500600892487
To link to this article: http://dx.doi.org/10.1080/10426500600892487
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Phosphorus, Sulfur, and Silicon, 182:175–179, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600892487
Simple and Practical Protocol for the Silylation of Phenol
Derivatives Using Reusable NaHSO4 Dispread on Silica
Gel Under Neutral Conditions
Mahideh S. Khalili
Hossein Ghafuri
Samaneh Mojahedi-Jahromi
Mohammed M. Hashemi
Department of Chemistry, Sharif University of Technology, Tehran, Iran
A simple and mild procedure for the trimethylsilylation of a wide variety of phe-
nols with hexamethyldisilazane (HMDS) on the surface of silica gel dispersed with
NaHSO at r.t. in a few minutes with excellent yields under neutral conditions
4
is reported. This procedure also allows an excellent selectivity for the silylation of
phenols in the presence of amine and CO H groups.
2
Keywords Hexamethyldisilazane (HMDS); hydroxy group; NaHSO4/SiO2; recycling;
selective silylation
INTRODUCTION
The trimethylsilylation of organic compounds having mobile hydrogen
atoms is an important organic transformation.1 It is a frequently used
protection method in multistep synthesis of natural products due to the
enhanced stability of the silyl derivatives under a variety of conditions,
the solubility in nonpolar solvents, and the thermal stability and ease
of the removal of silylan groups. Desilylation is simply accomplished by
acid- or base-induced hydrolysis, which gives only unreactive siloxane
as a byproduct. Silylation is also extensively used for the derivatiza-
tion of hydroxy compounds in order to increase their volatility for gas
chromatography and mass spectrometry.2
A
wide variety of methods using silylating agents, such
as chlorotrimethylsilane and a base,3 bis-(trimethylsilyl)trifluoro
acetamide,4 allylsilanes together with an acid,5 and bistrimethylsilyl
ether,6 have been reported. However, these reagents require the ad-
dition of bases, and the difficulty in removing the ammonium salts is
Received March 20, 2006; accepted May 30, 2006.
175

176
M. S. Khalili et al.
frequently encountered. A longer reaction time is an additional disad-
vantage of these reagents.
Hexamethyldisilazane (HMDS) is frequently used for the
trimethylsilylation of hydroxy groups. HMDS is an inexpensive
and commercially available reagent. Its handling does not require
special precautions, and the workup is not time consuming because
the byproduct of the reaction ammonia can be easily removed from
the reaction medium. The low silylation power of HMDS is the main
drawback to its application. There are a variety of catalysts for activat-
ing this reagent, such as I27, (CH3)3SiCl,8 and K-10 montmorillionite.9
Recently, trimethylsilyl azide and LiClO4 were used as an efficient
reagent for the silylation of hydroxy groups in neat conditions.10
Organic reactions under solvent-free conditions are of great current
interest, particularly in relation to green chemistry. On the other hand,
organic reactions using reusable and water-tolerant catalysts also re-
ceived much attention in recent years. Therefore, organic reactions us-
ing simple and efficient catalysts under solvent-free conditions would be
the ideal methodology, provided that the catalysts show a high catalytic
activity.11
RESULTS AND DISCUSSION
As part of our research on the application of solid support in organic
synthesis under solvent-free conditions,12 we describe in this article a
simple method for the protection of phenol derivatives using a catalytic
amount of NaHSO4 dispersed on SiO2 under solvent-free conditions
and in organic solvents (Scheme 1).
By using different reaction conditions for the silylation of phenols
with HMDS, we found out that best results are obtained using NaHSO4
dispersed on SiO2 (chromatography grade, NaHSO4/SiO2 with 1:3 ratio,
0.2 g), HMDS (10 mmol) and ROH (10 mmol) at r.t. with solvent-free
conditions. Interestingly, reactions catalyzed by NaHSO4 or by silica
alone under solvent-free conditions resulted in low yields. In the case
of solid substrates, when the reaction is carried out in the presence
of an organic solvent (such as CH2Cl2,CH3CN, toluene, THF, or diethyl
ether), it is completed after long reaction times in comparison to solvent-
free conditions. NaHSO4 dispersed on SiO2 was used for the silylation
of the hydroxy group for a variety of phenols applying simple and highly
efficient reaction conditions. The results are summarized in Table I. All
1
HMDS ( eq), NaHSO4 / SiO2
ArOSiMe3
ArOH
r.t., neat or CH
2Cl2
SCHEME 1

Protocol for the Silylation of Phenol Derivatives
177
TABLE I The Silylation of Various Phenols with HMDS
ArOH
Time (min)
Yield (%)
OH
5
5
86
92
OH
Cl
Cl
Me
OH
5
5
89
90
Cl
OH
Me
MeO
OH
5
5
94
90
OH
OH
100
5
00
94
90
93
O2N
Cl
OH
OH
5
t-Bu
Br
OH
5

178
M. S. Khalili et al.
4
HMDS ( mmol)
PhOH
+
PhCO2H
2 mmol
PhOSiMe3
90%
+
PhCO2SiMe3
0%
NaHSO /SiO ( 0.4g), r.t., min
5
4
2
2 mmol
4
HMDS ( mmol)
H2N
OH
OSiMe3
H2N
0.4
NaHSO4 /SiO2 (
g), r.t., 5 min
2 mmol
94%
SCHEME 2
phenol derivatives can be converted to corresponding trimethyl silyl
ethers under these conditions. The reactions are fast and proceed with
high yields at r.t. even for less reactive phenols, which usually require
long reaction times (a few days) when silylated by conventional reported
methods.
We also explored the chemoselectivity of the NaHSO4/SiO2 system.
Scheme 2 shows that in the presence of both a COOH and a phenolic
OH group, the phenolic hydroxy group is selectively silylated, and the
corresponding silylated phenol is the only reaction product. Similarly,
in the presence of an amino group, only the hydroxy group reacts with
HMDS to give the corresponding silylated phenol. Although the mech-
anism of this reaction is not clear, silica gel plays an important role,
and its presence was found to be essential for the high efficiency of the
reaction.
In summary, NaHSO4/SiO2 is found to be an efficient and useful
catalyst for the silylation of various phenols with HMDS under mild
and neutral conditions. This procedure provides an efficient and gen-
eral methodology for the preparation of phenol trimethylsilyl ethers
in high yields. In addition, NaHSO4/SiO2 is an inexpensive, stable,
easy-to-handle, and nontoxic reagent, and the workup is very simple.
NaHSO4/SiO2 can be reused several times after activation. Further-
more, HMDS in combination with the NaHSO4/SiO2 system exhibits ex-
cellent selectivity for the silylation of phenols in the presence of amines
and carbonic acids.
EXPERIMENTAL
The Preparation of the NaHSO4/SiO2 Catalyst
To a solution of 4.14 g (0.03 mol) of NaHSO4/SiO2 in 20-mL of wa-
ter in a 100-mL beaker containing a stir bar was added 10 g of SiO2

Protocol for the Silylation of Phenol Derivatives
179
˚
(column chromatographic grade, 60 A, 200–400 mesh). The mixture
was stirred for 15 min and then gently heated on a hotplate with in-
termittent swirling until a free-flowing white solid was obtained. The
catalyst was further dried by placing the beaker in an oven maintained
at 120◦C for at least 48 h prior to use.
The Silylation of Phenols Under Solvent-Free Conditions:
General Procedure
To a stirred solution of phenol (5 mmol) and 0.2 g of NaHSO4/SiO2
in a test tube, HMDS (5 mmol) was added and stirred at r.t. under an
argon atmosphere for the specified time (Table I). When the reaction was
complete (TLC or GC analysis), CH2Cl2 or petroleum ether (5 mL) was
added, and the NaHSO4/SiO2 was removed by filtration. The solvent
was evaporated, and the silylated phenol was isolated as an almost
pure crude product. Further purification if necessary was carried out by
short column chromatography on silica gel eluting with ethyl acetate-
petroleum ether. All silylated phenols prepared are known and were
identified on the basis of their spectroscopic data (IR, NMR).
REFERENCES
[1] (a) T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd
ed., p. 116, (Wiley, New York, 1999); (b) G. Sartori, R. Ballini, F. Bigi, G. Bosica,
R. Maggi, and P. Righi, Chem. Rev., 104, 199 (2004).
[2] B. E. Cooper, Chem. Ind., 794 (1978), and references cited therein.
[3] (a) R. West, J. Am. Chem. Soc., 80, 3246 (1958); (b) H. O. House, L. G. Czuba, M. Gall
and H. D. Olmstead, J. Org. Chem., 34, 2324 (1969); (c) E. J. Corey and B. B. Snider,
J. Am. Chem. Soc., 94, 2549 (1972).
[4] P. Chirakul, P. D. Hampton, and E. N. Duesler, Tetrahedron Lett., 39, 5473 (1998).
[5] T. Morita, Y. Okamoto, and H. Sakurai, Tetrahedron Lett., 21, 835 (1980).
[6] H. W. Pinnick, B. S. Bal, and N. H. Lajis, Tetrahedron Lett., 19, 4261 (1978).
[7] B. Karimi and B. J. Golshani, Org. Chem., 65, 7228 (2000).
[8] (a) S. H. Langer, S. Connell, and I. Wender, J. Org. Chem., 23, 50 (1958); (b) P.
Gauuret, S. El- Ghamarli, A. Legrand, D. Couirier, and B. Rigo, Synth. Commun.,
26, 707 (1996).
[9] Z. H. Zhang, T. S. Li, F. Yang, and C. G. Fu, Synth. Commun., 28, 3105 (1998).
[10] (a) N. Azizi and M. R. Saidi, Organometallics, 23, 1457 (2004); (b) D. Amantini,
F. Fringuelli, F. Pizzo, and L. Vaccaro, J. Org. Chem., 66, 6734 (2001).
[11] (a) K. Tanaka and F. Toda, Chem. Rev., 100, 1025 (2000); (b) J. O. Metzger, Angew.
Chem. Int. Ed., 37, 2975 (1998).
[12] M. M. Hashemi, H. Ghafuri, and Z. Karimi-Jaberi, Monatsh. Chem., 137, 197 (2006)