Efficient trimethylsilylation of alcohols and phenols with HMDS in the presence of a catalytic amount of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a safe and cheap industrial chemical

Article abstract of DOI:10.1002/jccs.200700068

1,3-Dibromo-5,5-dimethylhydantoin (DBDMH) is found to be an effective catalyst for trimethylsilylation various alcohols and phenols with hexamethyldisilazane (HMDS) in dichloromethane at room temperature.

Full text of DOI:10.1002/jccs.200700068

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Journal of the Chinese Chemical Society, 2007, 54, 483-487
483
Efficient Trimethylsilylation of Alcohols and Phenols with HMDS in the
Presence of a Catalytic Amount of 1,3-Dibromo-5,5-dimethylhydantoin
(DBDMH) as a Safe and Cheap Industrial Chemical
Ardeshir Khazaei,a* Amin Rostamib and Marjan Mahboubifara
aDepartment of Chemistry, Faculty of Science, Bu-Ali Sina University, Hamadan, 6517838683, Iran
bDepartment of Chemistry, Faculty of Science, Kurdistan University, Sanandaj, Iran
1,3-Dibromo-5,5-dimethylhydantoin (DBDMH) is found to be an effective catalyst for trimethyl-
silylation various alcohols and phenols with hexamethyldisilazane (HMDS) in dichloromethane at room
temperature.
Keywords: Alcohols; Phenols; Hexamethyldisilazane; 1,3-Dibromo-5,5-dimethylhydantion;
Trimethylsilyl ether.
INTRODUCTION
Many chemical conversions and multiple synthesis
N-halo compounds in organic synthesis,19 we have found
that 1,3-dibromo-5,5-dimethylhydantion (DBDMH) is an
inexpensive, commercially available reagent, which can be
used as an alternative to bromine or NBS. This safe indus-
trial chemical has never had a real breakthrough in organic
laboratories, and its use in organic chemistry is mostly lim-
ited to bromination and oxidation reactions.20 In this paper
we wish to report the catalytic application of 1,3-dibromo-
5,5-dimethylhydantoin (DBDMH) as a new protocol for
the mild trimetylsilylation of several alcohols and phenols
using HMDS in dichloromethane at room temperature
(Scheme I).
sequences often require protection of hydroxy groups. The
trimethylsilyl group is one of the most widely used pro-
tecting groups in organic synthesis and is often used to pre-
pare silyl ethers as volatile derivatives of alcohols and phe-
nols.1-4 One of the reported reagents for trimethylsilylation
is 1,1,1,3,3,3-hexamethyldisilazane (HMDS)5,6 which is a
cheap and commercially available reagent. Its handling
does not need special precautions; trimethylsilylation using
this reagent is nearly neutral and the work-up of the reac-
tion mixture is not time consuming. However the major dis-
advantage and drawback of this reagent is its poor silyl-
ating power, which needs forceful conditions and long re-
action times in many reactions. Hence, a variety of cata-
lysts have been reported for the activation of HMDS.7-18
However, in most cases drastic reaction conditions and te-
dious workup are needed and reactions using hindered al-
cohols do not occur. In addition, many of these reagents are
moisture sensitive, toxic and expensive. The lack of a facile
and general synthetic methodology for the trimethylsilyla-
tion of hydroxyl groups (alcohols, phenols), under neutral
conditions, prompted us to develop an efficient and conve-
nient procedure for the protection of hydroxyl groups under
mild conditions.
Scheme I
,
DBDMH (0.01-0.1 mmol)
HMDS (0.7-5 mmol)
R
OH
R OSiMe3
,
CH2Cl2
rt
R=Alkyl, Aryl
Br
O
N
O
N
Br
DBDMH
We first examined the effect of different ratios of
ROH/HMDS/catalyst. The 1/2/0.01 and 1/0.7/0.01 ratios
for alcohols and phenols respectively gave the best results
and produced trimethylsilyl ethers in quantitative yields
(Tables 1, 2).
RESULTS AND DISCUSSION
In continuation of our interest in the application of

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484 J. Chin. Chem. Soc., Vol. 54, No. 2, 2007
Khazaei et al.
Table 1. Trimethlysilylation of alcohols using HMDS catalyzed with DBDMH in dichloromethane at
room temperature
Entry
ROH
Subst/HMDS/DBDMH Time (h:min)
Yield (%)a,b
1
2
3
4
5
6
PhCH2OH
1:2:0.01
1:2:0.01
1:2:0.01
1:2:0.01
1:2:0.01
1:2:0.01
1:06
84
95
96
93
99
95
4-CH3-C6H4CH2OH
4-Br-C6H4CH2OH
4-F-C6H4CH2OH
2,4-(Cl)2C6H4CH2OH
4--NO2-C6H4CH2OH
2
1:18
2
1
1
7
1:2:0.01
2
92
CH2CH2OH
8
1:2:0.01
2:06
95
CH2CH2OH
9
CH3(CH2) 6CH2OH
PhCH (OH) Ph
1:2:0.01
1:2:0.01
0:40
4
87
90
10
O
OH
11
12
1:2:0.01
1:2:0.01
8:30
8:18
97
99
CH
C
OH
OH
13
1:0.8:0.01
1:27
80
14
15
16
CH3CH2CHOHCH2CH3
1-adamantanol
1:0.8:0.01
1:5:0.1
3
85
90
87
12
17
CH3C(CH3)(OH)CH2Ph
1:5:0.1
a All products were characterized by comparison of their spectral data (1H-NMR; IR) with those of
authentic samples.
b Yields of isolated products.
Table 2. Trimethylsilylation of phenols using HMDS catalyzed with DMDBH in
dichloromethane at room temperature
Entry
ROH
Subst/HMDS/DBDMH Time (min)
Yield (%)a,b
1
C6H5OH
1:0.7:0.01
1:0.7:0.01
1:0.7:0.01
1:0.7:0.01
1:0.7:0.01
1:0.7:0.01
1:2:0.01
25
95
97
96
96
90
95
70
30c
0
2
4-(CH3)C6H4OH
4-(MeO)C6H4OH
4-(Cl)C6H4OH
2-Naphthol
1
3
1
4
15
5
1
6
1-Naphthol
20
7
Resorcinol
67
180
48h
48h
8
2,6-Diisopropyl phenol
C6H5NH2
1:0.7:0.01
1:2:0.01
9
10
C6H5SH
1:2:0.01
0
a All products were characterized by comparison of their spectral data (1H-NMR; IR) with
those of authentic samples.
b Yields of isolated products.
c Reaction did not complete.

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Trimethylsilylation of Alcohols and Phenols
J. Chin. Chem. Soc., Vol. 54, No. 2, 2007 485
Treatment of several alcohols with HMDS and the
catalyst in dichloromethane at room temperature produced
the corresponding trimethylsilyl ether in excellent yields
(Table 1). Interestingly, tertiary and acid-sensitive tertiary
alcohols were converted to the corresponding silyl ether at
room temperature; their trimethylsilylation required longer
reaction times and greater amount of HMDS and reagents
at room temperature (Table 1, entries 15, 16). Due to the
nearly neutral nature of the reaction medium, there were
not any side products.
The data in Table 2 clearly show that different types
of phenols were successfully converted to the correspond-
ing silyl ethers in a short time and in almost quantitative
yields. We observed that amines and thiols were not con-
verted under this reaction even after prolonged reaction
times. (Table 2, entries 9, 10).
In order to show selectivity of this catalytic system,
we tried several competitive reactions under similar condi-
Table 3. Selective reactions of different binary mixtures with HMDS/DBDMH at room temperature
OSi(CH3)3
OH
(100%)
(0%)
,
DBDMH (0.01 mmol), HMDS (2 mmol)
1
OSi(CH3)3
,
OH
CH2Cl2
0.67h
(100%)
(0%)
OH
DBDMH (0.01 mmol), HMDS (2 mmol)
OSi(CH3)3
OSi(CH3)3
2
OH
,
CH2Cl2
3h
OH
OSi(CH3)2
(100%)
CH3
CH3
DBDMH (0.01 mmol), HMDS (0.7 mmol)
3
,
CH2Cl2
CH(CH3)2
2min
OSi(CH3)3
OH
CH(CH3)2
(H3C)2HC
(H3C)2HC
(0%)
OSi(CH3)3
OH
(100%)
(0%)
DBDMH (0.01 mmol), HMDS (0.7 mmol)
4
NH2
,
NHOSi(CH3)3
CH2Cl2
25min
OSi(CH3)3
SSi(CH3)3
OH
SH
(100%)
(0%)
DBDMH. (0.01 mmol), HMDS (0.7 mmol)
5
,
CH2Cl2
25min

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486 J. Chin. Chem. Soc., Vol. 54, No. 2, 2007
Khazaei et al.
tions. In a binary mixture of n-octanol (as a model for pri-
mary alcohol) and 1-adamantanol (as a model for tertiary
alcohol), the primary alcohol was completely converted to
the corresponding silylether, while 0% conversion was ob-
served for the tertiary alcohol (Table 3, entry 1). Excellent
selectivity was also observed for secondary alcohols in the
presence of a tertiary alcohol (Table 3, entry 2).
trimethylsilylation reactions (as a protic acid). DHDMH
may act as an alternative as a source for the formation of
Br+. However, at this time the precise role of DBDMH is
not clear and the actual role of this reagent should be fur-
ther studied in detail.
In conclusion, our methodology shows that 1,3-di-
bromo-5,5-dimethylhydantoin (DBDMH) is an effective
and practically neutral catalyst for trimethylsilylation of
various hydroxyl groups using HMDS. The main advan-
tages of our protocol are: fast reaction, selectivity, excel-
lent yields, low cost reagent, and easy work-up conditions.
For these reasons our protocol compares favorably to the
existing methodologies in the field of protection of the
hydroxyl group as TMS-ether.
Similarly, we used this procedure for the selective
trimethylsilylation of 4-methyl phenol in the presence of
2,6-diisopropyl phenol (as a model for hindered phenol).
The only observed product was 4-methyl phenyl trimethyl-
silyl ether in 100% conversion (Table 3, entry 3). Also this
method showed excellent selectivity for the conversion of
phenol in the presence of aniline or thiophenol (Table 3, en-
tries 4, 5).
In order to learn the catalytic activity of DBDMH, we
compared our obtained results for the trimethylsilylation of
1-naphtol (as a model for phenols) with the best of the well
known data from the literature (Table 4). The advantages or
the characteristic aspects of the described method in this
communication in comparison with other previously re-
ported catalysts are the following: a variety of phenols14,7
can be trimethylsilylated in good to high yield15,18 at room
temperature.18,16 In addition, the catalyst DBDMH is inex-
pensive, no moisture sensitivity15 and no large amount of
catalyst required.15
EXPERIMENTAL SECTION
General Procedure
To a mixture of HMDS (0.7-2 mmol) and DBDMH
(0.01-0.1 mmol) in CH2Cl2 (7 mL) alcohols or phenols (1
mmol) were added, and the mixture was stirred at room
temperature for the specified time (Tables 1, 2). The prog-
ress was monitored by TLC. After completion of the reac-
tion, water (10 mL) was added to destroy the extra amounts
of HMDS for alcohols and NaOH %5 (10 mL) for phenols,
then the organic layer was separated and dried over anhy-
drous Na2SO4. The solvent was evaporated, and n-hexane
(20 mL) was added to the residual solid. Insoluble catalyst
was removed by filtration. Evaporation of the n-hexane un-
der reduced pressure gave pure product without further pu-
rification.
The actual role of DBDMH is not clear. On the basis
of a previously reported mechanism for applying I2 for the
trimethylsilylation of alcohols using HMDS14 and our ob-
servation during the course of the reaction (evolution of
acid), a hypothesis is that DBDMH may generate small
quantities of HBr, which may be the actual catalyst for the
Table 4. Comparison of the activity of various catalysts in the trimethylsilylation of 1-naphtol with HMDS
OSi(CH3)3
OH
Catalyst
HMDS
Entry
Catalyst
DBDMH
CuSO4.5H2O CH3CN, reflux
Condition
HMDS:Cat
Time
Yield (%)
Ref
1
2
3
5
6
7
CH2Cl2, rt
0.8:0.06
0.7:0.1
30 min
95
50
80
-
This work
38 h
18
15
16
14
7
LiClO4
Solvent-Free, rt
0.7:0.5
20 min
H3PW12O40*
I2
Solvent-Free, 55 °C-60 °C
CH2Cl2, rt
0.8:0.01
-
-
-
0.8:0.01
-
Si(CH3)3Cl
Solvent-Free, 125 °C
0.8:two drops
-
* Reaction with other derivatives of phenols has been reported.