1,3-Dichloro-5,5-dimethylhydantoin (DCH) and trichloromelamine (TCM) as efficient catalysts for the chemoselective trimethylsilylation of hydroxyl group with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) under mild conditions

Article abstract of DOI:10.1002/jccs.200900037

A highly convenient method for the trimethylsilylation of alcohols and phenols via treatment by hexamethyldisilazane in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCH) and/or trichloromelamine (TCM) as a catalyst has been developed. A wide variety of hydroxyl groups were selectively protected in CH₂Cl₂/CH₃CN under mild conditions.

Full text of DOI:10.1002/jccs.200900037

Journal of the Chinese Chemical Society, 2009, 56, 255-260
255
Communication
1,3-Dichloro-5,5-dimethylhydantoin (DCH) and Trichloromelamine (TCM)
as Efficient Catalysts for the Chemoselective Trimethylsilylation of
Hydroxyl Group with 1,1,1,3,3,3-Hexamethyldisilazane (HMDS) under Mild
Conditions
a
Arash Ghorbani-Choghamarani, * Kamal Amani, Mohammad Ali Zolfigol,
b
c
b
c
Maryam Hajjami and Roia Ayazi-Nasrabadi
Department of Chemistry, Faculty of Science, Ilam University, P.O. Box 69315516, Ilam, Iran
a
b
Department of Chemistry, Faculty of Science, University of Kurdistan, P.O. Box 6617715175,
Sanandaj, Iran
c
Faculty of Chemistry, Bu-Ali Sina University, P.O. Box 6517838683, Hamadan, Iran
A highly convenient method for the trimethylsilylation of alcohols and phenols via treatment by
hexamethyldisilazane in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCH) and/or trichloromel-
amine (TCM) as a catalyst has been developed. A wide variety of hydroxyl groups were selectively pro-
2 2 3
tected in CH Cl /CH CN under mild conditions.
Keywords: 1,3-Dichloro-5,5-dimethylhydantoin (DCH); Trichloromelamine (TCM); Trimethyl-
silylation; Hexamethyldisilazane (HMDS).
Synthetic methodology, as the building block of or-
ganic synthesis, continuously seeks for new reagents,
better reaction conditions, and more efficient and selective
lack of reactivity or the difficulty in removal of by-prod-
ucts. 1,1,1,3,3,3-Hexamethyldisilazane (HMDS) as a cheap,
stable and commercially available reagent is one of the
most widely used reagent for silylation of hydroxyl groups.
Its handling does not require special precautions, and the
workup is not time-consuming, because the by-product of
the reaction is ammonia, which is simple to remove from
the reaction media. However, the low silylating power of
HMDS is the main drawback to its application. Therefore
to activate this reagent an appropriate catalyst should be
used.
1
methods. Silyl ethers are the most popular and useful pro-
tecting groups of the hydroxy function in synthetic organic
chemistry and various types of silyl ethers have been devel-
2
oped. Silylation of alcohols is an important process not
only as a protecting method of alcohols, but also for synthe-
3
sis of functional organosilicon compounds. Trimethyl-
silylation is used extensively for protection and derivatiza-
tion of most functional groups to increase volatility for gas
4
chromatography and mass spectrometry.
In continuation of our ongoing effort to develop new
1
methods in organic functional group transformations, es-
17
pecially for the protection of the hydroxyl groups, herein
6
Generally, the formation of silyl ethers carried out by
6
5
treatment of alcohols with trialkyl silyl halides or triflates
in the presence of a base. Other methods employ hexameth-
we disclose a very effective and mild procedure for the
trimethylsilyl protection of a wide variety of OH-contain-
ing substrates, including primary, secondary, benzylic, hin-
dered secondary, tertiary alcohols and some phenols using
hexamethyldisilazane (HMDS) in the presence of catalytic
amounts of two N-haloreagents entitled “1,3-dichloro-5,5-
dimethylhydantoin (DCH) and trichloromelamine (TCM)”
(Fig. 1), under mild conditions at room temperature.
7
yldisilazane, hydrosilanes, disilanes, alkylsilanes,
8
9
10
13
1
allylsilanes, trimethylsilyl azide, silylphosphines,
1
12
1
4
15
anilinosilane, or methallylsilanes in the presence of a
suitable catalyst. However, some of these methods basi-
cally suffered from serious obstacles such as low selectiv-
ity, long reaction times, low yields of products, toxicity, ex-
pensive reagents and catalysts, delicate purification step,
*
Corresponding author. Tel/Fax: +98-811-8257404; E-mail: arashghch58@yahoo.com

2
56 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Ghorbani-Choghamarani et al.
Table 1. Trimethylsilylation of benzyl alcohol using HMDS/
DCH a or HMDS/TCM b at room temperature in
a
different solvents
b
Time (Min)
Yield (%)
Entry
Solvent
a
b
a
b
1
2
3
4
5
6
Acetonitrile
Chloroform
030
240
120
180
180
015
065
135
045
180
180
100
100
100
100
100
100
Dichloromethane
n-Hexane
Ethyl acetate
Fig. 1.
c
c
--
c
--
c
--
--
d
e
e
Initially, we screened different solvents for the tri-
CH Cl
2
/CH CN
2 3
030 100 (93) 100 (92)
a
methylsilylation of benzyl alcohol with HMDS in the pres-
ence of a catalytic amount of DCH or TCM. As it can be
seen from Table 1, benzyl alcohol was silylated in aceto-
nitril faster than the other solvents. Also, result shown di-
chloromethane is in the second place. Therefore we de-
cided to chose a mixture of dichloromethane and acetonitril
Substrate/HMDS/DCH (1:0.8:0.03 mmol) or Substrate/HMDS/
TCM (1:0.8:0.03 mmol).
GC yield.
b
c
d
e
Trace conversion.
CH Cl :CH CN = 4:1 (ML).
Isolated yield.
2
2
3
(
4:1 mL) because of easy work up of silylated products and
Eventually, we wish to report here selective trimeth-
ylsilylation of different types of hydroxyl groups including
activity of this solvent mixture (Table 1).
Scheme I

Trimethylsilylation of Alcohols and Phenols
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 257
primary, secondary and tertiary alcohols using 1,1,1,3,3,3-
hexamethyldisilazane (HMDS) I in the presence of a cata-
lytic amount of 1,3-dichloro-5,5-dimethylhydantoin (DCH)
II or trichloromelamine (TCM) III in the mixture of di-
chloromethane/acetonitril (4:1 mL) at room temperature
with good to excellent yields (Scheme I and Table 2).
Table 2. Trimethylsilylation of alcohols 1 to the corresponding trimethylsilyl alcohols 2 using
HMDS I in the presence of a catalytic amount of DCH II or TCM III in the mixture
of CH Cl /CH CN (4:1 mL) at room temperature
2
2
3
Substrate/HMDS/Catalysts (mmol)
a
Entry Substrate Product
Time (Min) Yield (%)
I
II
III
1
2
3
4
5
6
7
8
9
1
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
2a
2a
2b
2b
2c
2c
2d
2d
2e
2e
2f
0.8
0.8
0.8
1.3
0.8
1.3
1.6
1.8
0.8
1.4
0.8
1.6
1.2
1.6
0.8
1.2
0.8
1.3
0.8
1.3
0.8
2
0.03
--
--
0.03
--
15
30
20
10
5
93
92
88
90
90
98
98
90
81
80
97
98
0.03
--
0.07
--
0.03
--
0.07
--
5
0.1
--
150
150
85
10
40
7
0.11
--
0.03
--
0
0.08
--
11
0.03
--
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
a
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
1f
2f
0.03
--
b
1g
1g
1h
1h
1i
2g
2g
2h
2h
2i
0.06
--
20
15
10
5
94
98
b
0.1
--
0.03
--
89
87
0.06
--
b
0.04
--
25
25
25
25
10
35
20
10
20
10
15
20
30
60
20
25
20
25
15
10
30
10
6h
80
120
30
91
85
91
b
b
1i
2i
0.08
--
1j
2j
0.04
--
b
1j
2j
0.08
--
100
87
90
96
82
89
94
82
94
98
90
93
98
98
98
100
100
81
96
1k
1k
1l
2k
2k
2l
0.03
--
0.1
--
0.8
1.7
1.1
1.6
0.8
1.4
0.8
1.3
0.8
1.3
0.8
1.5
0.8
1.3
1.1
1.6
4
0.03
--
1l
2l
0.1
--
1m
1m
1n
1n
1o
1o
1p
1p
1q
1q
1r
1r
1s
2m
2m
2n
2n
2o
2o
2p
2p
2q
2q
2r
2r
2s
0.07
-
0.11
--
0.03
--
0.08
--
0.05
--
0.09
--
0.03
--
0.07
--
0.03
--
0.07
--
b
b
0.03
--
0.07
--
0.07
--
1s
2s
0.11
--
b
1t
2t
0.14
--
72
95
89
93
1t
2t
2.6
0.8
1.3
0.18
--
1u
1u
2u
2u
0.05
--
0.09
Isolated yield.
GC yield.
b

2
58 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Ghorbani-Choghamarani et al.
To show the reactivity of described system some hy-
tion with hexamethyldisilazane in the presence of catalytic
amounts of DCH or TCM and found that only phenols were
silylated (Scheme II, Table 3).
drogen-labile substrates in addition to alcohols; such as
phenols, amines and thiols were subject to trimethylsilyla-
Scheme II
Table 3. Trimethylsilylation of phenols, amines and thiols to the corresponding trimethyl-
silylated products using HMDS I in the presence of a catalytic amount of DCH II or
TCM III in the mixture of CH Cl /CH CN (4:1 mL) at room temperature
2
2
3
Substrate/HMDS/Catalysts (mmol)
a
Entry
Substrate
Product
Time (h) Yield (%)
I
II
III
1
2
3
4
5
6
7
8
9
3a
3a
3b
3b
3c
3c
5a
5a
5b
5b
7a
7a
4a
4a
4b
4b
4c
4c
6a
6a
6b
6b
8a
8a
2
0.06
--
--
0.1
--
3.5
5
97
100
86
3
2.5
3
0.06
--
3
0.1
--
4
95
2.5
3
0.06
--
1.5
5
83
0.1
--
99
b
0.8
0.8
0.8
0.8
0.8
0.8
0.03
--
5
--
b
0.03
--
5
--
b
0.03
--
5
--
b
1
0
0.03
--
5
--
b
11
0.03
--
5
--
b
1
2
0.03
5
--
a
GC yield.
b
No reaction.

Trimethylsilylation of Alcohols and Phenols
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 259
A plausible mechanism of this reaction is shown in
7
Scheme III based on reported pathway in literatures,
ACKNOWLEDGMENT
b,7d,18
Financial support for this work by the Center of Ex-
cellence of Development of Chemical Methods (CEDCM)
of Bu-Ali Sina University, Hamadan, Iran is gratefully
acknowledged.
our observations and obtained results. N-Chloro catalysts
+
act as a source of Cl , which polarizes the Si-N bond in
HMDS to produce active silylating agent.
Received November 3, 2008.
Scheme III
Me SiNHSiMe3
3
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