A Convenient Method for Protection and Deprotection of Alcohols and Phenols as Alkylsilyl Ethers Catalyzed by Iodine under Microwave Irradiation

Article abstract of DOI:10.1081/scc-120026335

Irradiation of alcohols or phenols with tert-butyldimethylsilyl chloride (TBDMSCl) or trimethylsilyl chloride (TMSCl) in presence of catalytic amount (20 mol%) of iodine in a microwave oven for 2 min gives the corresponding silyl ethers in excellent yield. Iodine in methanol deprotects the silyl ether into its parent alcohol or phenol under similar reaction conditions.

Full text of DOI:10.1081/scc-120026335

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A Convenient Method for Protection and Deprotection
of Alcohols and Phenols as Alkylsilyl Ethers Catalyzed
by Iodine Under Microwave Irradiation
Ira Saxena a , Nabajyoti Deka a , Jadab C. Sarma a c & Sadao Tsuboi b
a Organic Chemistry Division, Regional Research Laboratory, Jorhat, Assam, India
b Department of Environmental Chemistry and Materials, Okayama University, Okayama,
Japan
c JSPS Fellow in the Department of Environmental Chemistry and Materials, Okayama
University, Tsushima, Okayama 700-8530, Japan, during November 2000 to September 2001
Version of record first published: 16 Aug 2006.
To cite this article: Ira Saxena , Nabajyoti Deka , Jadab C. Sarma & Sadao Tsuboi (2003): A Convenient Method for Protection
and Deprotection of Alcohols and Phenols as Alkylsilyl Ethers Catalyzed by Iodine Under Microwave Irradiation, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:23, 4185-4191
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 23, pp. 4005–4011, 2003
A Convenient Method for Protection and
Deprotection of Alcohols and Phenols as
Alkylsilyl Ethers Catalyzed by Iodine
Under Microwave Irradiation
,#
Ira Saxena,1 Nabajyoti Deka,1 Jadab C. Sarma,1,
*
and Sadao Tsuboi2,
*
1Organic Chemistry Division,
Regional Research Laboratory, Jorhat, Assam, India
2Department of Environmental Chemistry and
Materials, Okayama University, Okayama, Japan
ABSTRACT
Irradiation of alcohols or phenols with tert-butyldimethylsilyl
chloride (TBDMSCl) or trimethylsilyl chloride (TMSCl) in presence
*Correspondence: Jadab C. Sarma, Organic Chemistry Division, Regional
Research Laboratory, Jorhat 785006, Assam, India; Fax: 91-376-2370011;
E-mail: sarmajc@yahoo.co.in. Sadao Tsuboi, Department of Environmental
Chemistry and Materials, Okayama University, Tsushima, Okayama 700-8530,
Japan; Fax: 81-86-2518898; E-mail: stsuboi6@cc.okayama-u.ac.jp.
#JSPS Fellow in the Department of Environmental Chemistry and Materials,
Okayama University, Tsushima, Okayama 700-8530, Japan during November
2000 to September 2001.
4005
DOI: 10.1081/SCC-120026335
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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4006
Saxena et al.
of catalytic amount (20 mol%) of iodine in a microwave oven for
2 min gives the corresponding silyl ethers in excellent yield. Iodine in
methanol deprotects the silyl ether into its parent alcohol or phenol
under similar reaction conditions.
Key Words: O-Silylation; TBDMS ether; TMS ether; Iodine
catalyzed; Microwave irradiation.
O-Silylation of alcohols was mainly a derivatization process to
increase the volatility and stability of polar organic compounds in
gas chromatographic analysis.[1] But after early 70’s, the potential of
silyl group as a hydroxyl group protecting agent was acknowledged
and gradually it became the most widely used alcohol protecting
group.[2] tert-Butyldimethylsilyl (TBDMS) as well as trimethylsilyl
(TMS) protecting groups are seen to have wide application in synthetic
sequences of organic molecules, especially natural products like prosta-
glandin,[3] steroid,[4] carbohydrate etc.[5] In addition to its use as a hydroxyl
protecting group, the silyl group has the ability to control stereoselectivity
in many reactions.[6] The most common method of silylation of alcohol is
the reaction with trialkylsilyl chloride and a suitable base.[2]
Few other important reagents described for the preparation of TMS
ether are HMDS with TMSCl,[7] N,O-bis(trimethylsilyl)acetamide,[8]
1-(trimethylsilyl)imidazole,[9] TMSCl-Li2S,[10] or Mg.[11] Upadhya
et al.[12] had reported natural kaolinite clay as a catalyst for O-trimethyl-
silylation reaction while Karimi and Golshani[13] reported iodine as a
catalyst with HMDS.
R-OH TꢀBꢀDꢀMꢀSꢀCꢀl=ꢀIꢀ2 ꢀorꢀTꢀMꢀSꢀC!l=I2 R-OSiR3
Microwave
Recently Amantini et al.[14] had reported a method of O-trimethyl-
silylation of alcohol and phenol using trimethylsilylazide catalyzed by
tetrabutylammonium bromide under solvent free condition. But there is
no corresponding reagent for tert-butyldimethylsilyl ether formation. For
the preparation of the tert-butyldimethylsilyl ether of alcohol the most
commonly used reagent is the TBDMSCl with imidazole in DMF.[15]
For tertiary and hindered secondary alcohols tert-butyldimethylsilyl
triflate with 2,6-lutidine as base is used.[16] Few other reagents for this
conversion are TBDMSCl with Li2S,[10] TBDMSCl with DMAP and
trimethylamine,[17] allyl-tert-butyldimethylsilane with p-toluenesulfonic
acid[18] etc.
Herein, we wish to report a new commercially available cheap
catalyst for silylation of alcohol and phenol with TBDMSCl or

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Irradiation of Alcohols and Phenols
4007
TMSCl. During the course of our endeavour for development of environ-
ment friendly synthetic methods, utilization of microwave dielectric
heating effect has been studied in few reactions with iodine as a catalyst.
Use of microwave irradiation in organic reactions is advantageous in
many ways because of short reaction time, cleaner reaction products,
and solvent free reaction conditions.[19] Although different hypotheses
have been put forwarded to account for the effect of microwave on
organic reactions/compounds[20] the reason for the dramatic acceleration
effect is thought to be instantaneous super heating of the reaction
medium. Regardless of the exact origin of the microwave effect, it is
found to be extremely efficient and applicable to a very broad range of
practical syntheses including combinatorial one.[21] In this laboratory
also reactions like acetalization,[22] enol-acetylation,[23] DHP ether
formation,[24] etc., were performed under microwave irradiation.[25]
Continuing the same effort when an alcohol in 1,2-dichloroethane was
irradiated with TMSCl in a microwave oven at 90 W power or with
TBDMSCl at 360 W power and catalytic amount (20 mol%) of iodine
for about 2 min the corresponding silyl ether was formed in excellent
yield. Primary, secondary, and tertiary as well as allylic, benzylic, and
phenolic hydroxyl groups were easily transformed into the corresponding
silyl ethers. The results are presented in Table 1.
From the Table 1, it is clear that the reaction is high yielding with
yields ranging from 91 to 96% within a short period of time. Although
the existing methods for TMS ether formation gives similar yields, most
of these methods take several hours for completion at r.t. In case
of TBDMS ether the present method has the advantage of short
reaction time and high yield. The reagent is equally suitable for primary,
secondary, tertiary as well as allylic, benzylic, and phenolic hydroxyl
groups. When 1.5 M equiv. of TBDMSCl is used the yield of the corre-
sponding silyl ether is around 60 to 68% with recovery of the unreacted
starting material during purification. If we consider the yield based on
reacted starting material (BRSM) the actual yield turns out to be more
than 90%. When the molar equivalent of TBDMSCl added is increased
to 2.5 equiv., the yield of the TBDMS ether increased to around 95%.
Most of the time it is observed that a catalyst used for protection of a
functional group can also act as a deprotecting reagent if used alone
under some harsher conditions. In case of trimethylsilyl ether and tert-
butyldimethylsilyl ether, deprotection is generally done with a mild acidic
solution or with a flouride ion.[2] We have also observed like Vaino and
Szarek[28] that iodine acts as a deprotecting reagent for conversion of
TMS ether and TBDMS ether into their parent alcohol under microwave
irradiation in methanol at 360 and 640 W of power respectively. All the

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4008
Saxena et al.
Table 1. Formation of silyl ethers with TMSCl–iodine and TBDMSCl–iodine.a
Yield % at 90 W
with TMSCl
1.3 M equiv.
Yield % at 360 W
with TBDMSCl
1.5 M equiv. (BRSM) equiv. Ref.
Yield %
at 2.5 M
Substrate
[26a]
Hexadecanol
1-Docosanol
2,2,2-Trichloroethanol
Cyclohexanol
Cholesterol
96
92
92
93
94
94
93
90
91
92
95
94
94
94
93
95
94
68 (93)
65 (96)
63 (93)
62 (97)
62 (92)
68 (95)
67 (93)
67
94
95
92
95
93
95
94
92
94
92
94
95
94
95
93
94
94
[26b]
[26c]
[10]
[17]
[12]
[14]
[12]
[26d]
[14]
[10]
[27]
[27]
[12]
[14]
[10]
[26e]
1-Menthol
Borneol
t-Butanol
Terpeneol
Linalool
66
67 (91)
65 (95)
66 (94)
68 (93)
63
Benzyl alcohol
p-Anisyl alcohol
1-Phenylethanol
Allyl alcohol
Cinnamyl alcohol
Phenol
68 (87)
64 (94)
65 (93)
O-Cresol
aThe products were characterized by spectral (IR, NMR, MS) analysis as well as
comparison with authentic materials prepared by known methods.
silyl ethers reported in Table 1 were deprotected by iodine to the
corresponding alcohols in quantitative yield.
EXPERIMENTAL SECTION
General Procedure for Silylation of Hydroxyl Groups
To a solution of 2 mmol of an alcohol or phenol in 1.5 mL of 1,2-
dichloroethane was added 2.6 mmol of TMSCl or 3 mmol of TBDMSCl
(as the case may be) and 52 mg (0.2 mmol) of iodine. The solution was
taken in a 50 mL conical flask and placed in a kitchen type microwave
oven[25] (LG brand, model MS-28MC ‘‘multiwave’’). A small funnel was
placed in the mouth of the flask to reduce possible loss of solvent by
evaporation. The solution was irradiated at 90 W of power for TMS ether
and 360 W of power for TBDMS ether for 120 s (Table 1). The tempera-

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Irradiation of Alcohols and Phenols
4009
ture of the reaction mixture was between 46 to 50ꢁC for TMS ether and
71 to 72ꢁC for TBDMS ether when recorded immediately after irradia-
tion. The solution was diluted with dichloromethane, washed with a
dilute solution of sodium thiosulfate followed by water and dried
over anhydrous sodium sulfate. Evaporation of the solvent at reduced
pressure yielded almost pure product. Purification through a short
column was done when necessary.
General Procedure for Desilylation of Silyl Ethers
To a solution of 2 mmol of silyl ether in 1.5 mL of methanol was
added 0.2 mmol of iodine and the solution was irradiated in a microwave
oven for 130–180 s at a power setting of 360 W for TMS ether and 640 W
for TBDMS ether as described in the previous experimental procedure.
Work up in the similar way afforded a quantitative yield of the corre-
sponding alcohol, which was confirmed by comparison with the authentic
material.
ACKNOWLEDGMENT
Authors are grateful to the Director, RRL Jorhat for providing the
facilities, ND & IS thank CSIR for their Senior Research Fellowships
and JCS thanks JSPS for the invitation Fellowship.
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4010
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Irradiation of Alcohols and Phenols
4011
26. NMR (60 MHz) peaks of the TBDMS ether at ꢀ ppm are (a) 3.40
(t, J ¼ 6 Hz, 2H), 1.14 (m, 28H), 0.82 (s, 9H), 0.78 (t, J ¼ 6 Hz, 3H),
0.20 (s, 6H); (b) 3.38 (t, J ¼ 6 Hz, 2H), 1.13 (m, 40H), 0.80 (s, 9H),
0.76 (t, J ¼ 6 Hz, 3H), 0.20 (s, 6H); (c) 4.00 (br s, 2H), 0.90 (s,
9H), 0.30 (s, 6H); (d) 6.15 (m, 1H), 3.25 (m, 1H), 2.20 (m, 6H),
2.02 (s, 3H), 1.80 (s, 6H), 0.78 (s, 9H), 0.20 (s, 6H); (e) 6.30–7.00
(m, 4H), 1.90 (s, 3H), 0.70 (s, 9H), 0.10 (s, 6H).
27. Piva, O.; Amougay, A.; Pete, J.P. Tetrahedron Lett. 1991, 32, 3993.
28. Vaino, A.R.; Szarek, W.A. Chem. Commun. 1996, 2351.
Received in India June 7, 2003

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