Rapid and highly efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) catalysed by in situ generated I2 using Oxone /KI or cerium ammonium nitrate (CAN)/KI systems under mild conditions

Article abstract of DOI:10.1007/s12039-011-0120-5

Structurally diverse alcohols and phenols were trimethylsilylated in clean and efficient reactions with hexamethyldisilazane (HMDS) in the presence of a catalytic amount of I₂ generated in situ from Oxone /KI or CAN/KI systems. The reactions occur rapidly in good to high yields in wet CH₂Cl₂ at room temperature. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0120-5

c
J. Chem. Sci. Vol. 123, No. 5, September 2011, pp. 703–708. ꢀ Indian Academy of Sciences.
Rapid and highly efficient trimethylsilylation of alcohols and phenols
with hexamethyldisilazane (HMDS) catalysed by in situ generated I2
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using Oxoneꢀ/KI or cerium ammonium nitrate (CAN)/KI systems
under mild conditions
ESKANDAR KOLVARIa,∗, ARDESHIR KHAZAEIb,∗, MOHAMMAD ALI ZOLFIGOLb,∗
NADIYA KOUKABIb, MARYAM GILANDOUSTb and NEDA BAKHITb
,
aDepartment of Chemistry, Faculty of Science, Semnan University, Semnan, Iran
bFaculty of Chemistry, Bu-Ali Sina University, Hamedan, Post Box No. 4135, Iran
e-mail: kolvari@semnan.ac.ir; khazaei_1326@yahoo.com; zolfi@basu.ac.ir
MS received 9 February 2010; revised 31 January 2011; accepted 24 June 2011
Abstract. Structurally diverse alcohols and phenols were trimethylsilylated in clean and efficient reactions
with hexamethyldisilazane (HMDS) in the presence of a catalytic amount of I2 generated in situ from
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Oxoneꢀ/KI or CAN/KI systems. The reactions occur rapidly in good to high yields in wet CH2Cl2 at room
temperature.
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Keywords. Alcohols; phenols; hexamethyldisilazane; Oxoneꢀ/KI; CAN/KI; in situ generated I2;
trimethylsilylation.
1. Introduction
anamides;14 sulfamic acid;15 have been reported.
Although these catalysts provide an improvement, usu-
Protection of hydroxy group is a common practice ally low selectivity, forceful conditions, and long reac-
in organic chemistry. Among the protective groups, tion times have been observed in some of these reports.
silyl ethers are extensively utilized in analytical and in
Recently, the highly efficient method for trimethylsi-
preparative organic synthesis.1,2 Several methods are lylation of alcohols (not phenols) using HMDS catal-
available for the silylation of alcohols using a vari- ysed by molecular iodine in CH2Cl2 has been reported.9
ety of silylating agents.2 The use of some silylating Although molecular iodine is a versatile reagent in
agents is limited by their unavailability or the labo- organic synthesis,16 it is highly corrosive, toxic, and
rious processes of purifying the products. 1,1,1,3,3,3- sublimable, making its use somewhat unattractive. In
Hexamethyldisilazane (HMDS) is a stable, inexpensive, order to overcome these disadvantages with molecular
and commercially available reagent that can be used iodine, Bailey et al. reported a convenient method for in
for the preparation of trimethylsilyl ethers (TMS ethers) situ generation of I2 using CuSO4/NaI.17
from hydroxy compounds, giving ammonia as the only
Solid acids have many advantages such as sim-
by-product.3,4 Even though the handling of this reagent plicity in handling, decreased reactor and plant
is easy, its main drawback is its poor silylating abil- corrosion problems, and more environmentally safe
ity. Also forceful conditions and long reaction times disposal.18–20 Among solid acids, ceric ammonium
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are required.5 Therefore, for the activation of HMDS nitrate, Ce(NH4)2(NO3)6, (CAN), and Oxoneꢀ
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a variety of catalysts such as Envirocat EPZGꢀ;6 [2KHSO5 KHSO4 .K2SO4] are two commercially
montmorillonite clay;7 zirconium sulfophenyl phos- available inorganic oxidizing agents. There are sev-
phonate;8 molecular iodine;9 tungstophosphoric acid eral reports in the literature which demonstrate that
.
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(H3PW12O40);10 lithium perchlorate;11 aluminum tri- CAN and Oxoneꢀ are efficient reagents in organic
flate;12 cupric sulfate pentahydrate;13 N-bromo sulfo- reactions.21–23
∗For correspondence
703

704
Eskandar Kolvari et al.
Table 2. Comparison of various types of MX for the
trimethylsilylation of benzyl alcohol.a
2
2
2
Entry Oxidizer acid
MX
Time (h)
Yield (%)b
R
1
2
3
4
5
6
7
8
Oxoneꢀ
KI
KIc
immediateb
100
-
-
58
100
-
R
Oxoneꢀ
1
1
1
R
Oxoneꢀ
KCl
KBrc
KI
Scheme 1.
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Oxoneꢀ
CAN
CAN
CAN
CAN
immediate
KId
1
1
1
2. Experimental
KCl
-
60
KBrc
2.1 General
a
Reaction condition: Benzyl alcohol (1.0 mmol); oxidant
(0.2 mmol); MX (0.2 mmol); 1 mL moistened CH2Cl2. bThe
Chemicals were purchased from Fluka, Merck and
Aldrich chemical companies. Yields refer to isolated completion of the reaction was confirmed by TLC and GC.
cGC yield. d Solvent-free
pure products. The products were characterized by
comparison of their spectral (IR, H-NMR) and physi-
1
cal data with authentic samples.
the mixture was filtered and the solids were washed
with CH2Cl2 (5 mL). Powdered Na2S2O3 (2 g) was
2.2 Typical procedure for trimethylsilylation of
alcohols and phenols
added to the reaction mixture, then the mixture was
stirred for additional 5 min, and the resulting mixture
was filtered. Finally, H2O (10 mL) was added to destroy
the extra amount of HMDS, the organic layer was sep-
arated and the filtrate was dried (Na2SO4). Evaporation
of the solvent under reduced pressure gave almost pure
product.
The alcohol or phenol (1 mmol) was added to a mix-
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ture of CAN or Oxoneꢀ (0.2 mmol) and KI (0.2 mmol)
in CH2Cl2 (1 mL) and 0.05 mL of H2O. Then HMDS
(1 mmol in 1 mL CH2Cl2) was added drop-wise to this
mixture within 5 min. The mixture was stirred vig-
orously at room temperature for the specified time
(tables 4, 5). After completion of the reaction (TLC),
3. Results and discussion
In continuation of our studies using CAN24 and
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Oxoneꢀ 25–27 in organic transformations, we have
Table 1. Comparison between various oxidizing agents/
KI systems for the trimethylsilylation of benzyl alcohol.a
been interested in finding out a catalytic system for
trimethylsilylation of alcohols and phenols. In this
Entry
Oxidant
Time (h)
Yield (%)b
1
2
Na2S2O8
K2S2O8
2
2
-
-
Table 3. Comparison of various solvents for the
trimethylsilylation of benzyl alcohol using I2 generated in
3
4
5
6
7
8
9
10
11
12
Sodium perborate
(NH4)2S2O8
3
1
-
-
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situ from Oxoneꢀ (0.2 mmol) in the presence of a catalytic
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Oxoneꢀ
immediatec
100
100
-
-
-
amount of KI (0.2 mmol).
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Oxoneꢀ
6d
2
2
2
UHPe
Entry
Solvent
The amount of Time (h) Yield (%)a
solvent (ml)
DABCO–DNODPf
PVP–H2O g
2
1
2
3
4
5
6
7
8
CH3CN
CH3CN/H2O
CH2Cl2
CH2Cl2/H2O
CH2Cl2/H2O
THF/H2O
CHCl3/H2O
n-Hexane
2
2
2
2
2
60
75
-
80
100
60
85
-
Sodium percarbonate
CAN
CAN
3
immediatec
1b
-
2/0.05
2
100
100
5/0.05
2/0.05
2/0.05
2/0.05
2
aReaction condition: Benzyl alcohol (1.0 mmol); oxi-
dant (0.2 mmol); KI (0.2 mmol); 1 mL moistened
CH2Cl2; bGC yield; cThe completion of the reaction
was confirmed by TLC and GC; dWithout KI; eUrea
immediateb
2
2
2
f
Hydrogen Peroxide (UHP); 1,4-Diazabicyclo[2.2.2]octane
b
1,4-bis(oxide)-bis(hydrogen peroxide) (DABCO-DNODP);
aGC yield. The completion of the reaction was confirmed
gPolyvinylpyrrolidone- H2O2 (PVP-H2O2)
by TLC and GC

Trimethylsilylation of alcohols and phenols catalysed by in-situ generated I2
705
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Table 4. Trimethylsilylation of alcohols (1 mmol) using HMDS (1 mmol) catalysed with I2 generated in situ from Oxoneꢀ
(I) (0.2 mmol) or CAN (II) (0.2 mmol) in the presence of a catalytic amount of KI (0.2) in dichloromethane and 0.05 mL of
H2O at room temperature.
Entry
Substrate
Time (min)
Producta
Yield (%)b
II
I
II
I
28
28
1
2
PhCH2OH
4-MeO-C6H4CH2OH
immediatec immediatec
PhCH2OTMS
4-MeO-C6H4CH2OTMS
92
94
90
95
immediate
immediate
immediate
immediate
28
28
3
87
90
4
immediate
immediate
83
82
28
29
29
29
30
31
31
5
6
7
8
9
10
11
11
9
93
95
90
92
94
92
90
95
95
93
91
96
93
90
4-Cl-C6H4CH2OH
PhCH(OH)Ph
CH3(CH2)6CH2OH
2,4-(Cl)2C6H4CH2OH
PhCH2CH2OH
immediate
immediate
immediate
immediate
immediate
immediate
immediate
immediate
immediate
immediate
immediate
immediate
4-Cl-C6H4CH2OTMS
PhCH(OTMS)Ph
CH3(CH2)6CH2OTMS
2,4-(Cl)2C6H4CH2OTMS
PhCH2CH2OTMS
PhCH2CH2CH2OH
PhCH2CH2CH2OTMS
31
32
12
13
immediate
immediate
immediate
immediate
95
85
97
87
33
14
20
15
93
93
33
33
15
16
30
25
90
97
92
99
immediate
immediate
H CH3
H3C
H
H CH3
H3C
H
CH3
H
CH3
H
H
H
H
H
34
35
OH
OTMS
17
18
immediate
10
2
97
90
97
92
15

706
Eskandar Kolvari et al.
Table 4. (continued)
Entry
Substrate
Time (min)
Producta
II
Yield (%)b
II
I
I
36
36
19
20
30
40
45
35
83
87
85
90
aAll products were characterized by comparison of their spectral data (1H-NMR; IR) and with those of authentic samples.
bIsolated yield. cThe completion of the reactions were confirmed by TLC and GC
context, we have found that a combination of CAN
To find the best system for in situ generation of I2,
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or Oxoneꢀ and a catalytic amount of KI in the pres- first we studied a number of oxidizing agents in combi-
ence of HMDS generate in situ I2 as an efficient cata- nation of KI for the trimethylsilylation of alcohols and
lyst for the trimethylsilylation of alcohols and phenols phenols. As it can be seen in table 1, the best results are
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(scheme 1).
obtained from CAN/KI and Oxoneꢀ/KI systems.
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Table 5. Trimethylsilylation of phenols (1 mmol) using HMDS (1 mmol) catalysed with I2 generated in situ from Oxoneꢀ
(I) (0.2 mmol) or CAN (II) (0.2 mmol) in the presence of a catalytic amount of KI (0.2) in CH2Cl2 and 0.05 mL of H2O at
room temperature.
Entry
Substrate
Time (min)
Producta
II
Yield (%)b
II
I
I
immediatec
4
immediate
2
95
97
94
98
28
29
1
2
37
38
3
4
immediate
immediate
immediate
immediate
90
93
91
95
2
2
2
5
NR
NR
NR
NR
-
-
-
-
-
-
6
aAll products were characterized by comparison of their spectral data (1H-NMR; IR) with those of authentic samples.
bIsolated yields. cThe completion of the reactions were confirmed by TLC and GC

Trimethylsilylation of alcohols and phenols catalysed by in-situ generated I2
707
Apart from KI, we also used a catalytic amount of 4. Conclusion
KCl and KBr for the described system and the obtained
In summary, a mild method for the in situ generation of
results are depicted in table 2. From these results, it is
clear that KI is more efficient than KCl or KBr. Also
as a model we studied the trimethylsilylation of benzyl
alcohol in different solvents (table 3).
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I2 from inexpensive materials, CAN/KI or Oxoneꢀ /KI,
has been developed. The in situ generated I2 has been
shown to be an effective promoter for trimethylsilyla-
tion of variety alcohols and phenols using HMDS under
mild conditions.
Thus, in this article we wish to report the trimethylsi-
lylation of alcohols and phenols under mild and
homogeneous conditions. A variety of alcohols and
phenols were subjected to silylation reaction with a
Acknowledgements
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combination of CAN or Oxoneꢀ and a catalytic amount
We thank Semnan University Research Council,
Bu-Ali Sina University Research Council, and Center
of Excellence in Development of Chemical Methods
(CEDCM), national foundation of elites (BMN) for
supporting this work. Also, we thank Mr. Mehdi Damali
Amiri for his help in editing the manuscript.
of KI in the presence of HMDS. All protection reactions
were performed under mild and homogeneous condi-
tions, at room temperature with good to high yields.
These reactions were carried out in CH2Cl2 wetted by
0.05 mL of H2O (table 4).
As shown in table 4, in the cases of primary and sec-
ondary alcohols the reactions were completed rapidly.
Interestingly, different types of highly hindered tertiary
alcohols were successfully converted to the correspond-
ing trimethylsilyl ethers in almost quantitative yields at
room temperature (table 4, entries 18–20). Moreover no
side products were observed in these reactions.
The data in table 5 clearly show that different types of
phenols were successfully converted to the correspond-
ing silyl ethers in short reaction times and in almost
quantitative yields. We observed that amines and thiols
were not silylated under these reaction conditions even
after prolonged times (table 5, entries 5, 6).
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