Efficient synthesis of trimethylsilyl pseudohalides catalyzed by PEG400/ZnI2 under ultrasound irradiation

Article abstract of DOI:10.1081/SCC-200054856

Trimethylsilyl pseudohalides Me₃SiX, where X = NCS, NCO, or CN, were readily prepared conveniently in desirable yields by the reaction of Me₃SiCl with NaX or KX catalyzed by PEG400 and zinc iodide under ultrasound irradiation. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200054856

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Efficient Synthesis of
Trimethylsilyl Pseudohalides
Catalyzed by PEG400/ZnI2
under Ultrasound Irradiation
a
a b
b
Wang Sufang
, Wang Shaobing & Xu Yongshen
a
School of Chemical Engineering & Technology,
Tianjin University, Tianjin, China
b
Tianjin Research and Design Institute of Chemical
Industry, Dingzigu Hongqiao District, Tianjin, China
Published online: 16 Aug 2006.
To cite this article: Wang Sufang , Wang Shaobing & Xu Yongshen (2005): Efficient
Synthesis of Trimethylsilyl Pseudohalides Catalyzed by PEG400/ZnI under Ultrasound
2
Irradiation, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:9, 1271-1276
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Synthetic Communications , 35: 1271–1276, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200054856
Efficient Synthesis of Trimethylsilyl
Pseudohalides Catalyzed by PEG400/ZnI2
under Ultrasound Irradiation
Wang Sufang
School of Chemical Engineering & Technology, Tianjin University,
Tianjin, China and Tianjin Research and Design Institute of Chemical
Industry, Dingzigu Hongqiao District, Tianjin, China
Wang Shaobing
Tianjin Research and Design Institute of Chemical Industry, Dingzigu
Hongqiao District, Tianjin, China
Xu Yongshen
School of Chemical Engineering & Technology, Tianjin University,
Tianjin, China
Abstract: Trimethylsilyl pseudohalides Me SiX, where X ¼ NCS, NCO, or CN, were
3
3
readily prepared conveniently in desirable yields by the reaction of Me SiCl with NaX
or KX catalyzed by PEG400 and zinc iodide under ultrasound irradiation.
Keywords: Trimethylsilyl pseudohalides, trimethylsilyl chloride, PEG400, ultrasound
irradiation
Trimethylsilyl pseudohalides play important roles in a variety of synthetic
transformations. For example, trimethylsilyl cyanide is an effective reagent
for the preparation of b-amino alcohols, a-aminonitriles, and a-trimethyl-
[1]
siloxyacrylonitriles from the corresponding ketones, imines, and ketenes.
It can also react rapidly with the carbonyl of aldehydes to give silylated
Received in Japan November 10, 2004
Address correspondence to Xu Yongshen, School of Chemical Engineering &
Technology, Tianjin University, Tianjin, 300072 China. E-mail: chemistry_tjuv@
yahoo.com.cn

1272
W. Sufang, W. Shaobing, and X. Yongshen
cyanohydrins, which have found to be useful as acyl anion equivalents in
[
2]
many synthetic reactions. Trimethylsilyl isothiocyanate has been widely
accepted as an efficient reagent for the C-terminal sequencing of proteins
[
3]
and peptides. Trimethylsilyl isocyanate has been applied to the synthesis
[
4]
of primary amides from Grignard reagent. In summary, trimethylsilyl pseu-
dohalides are a class of important and useful reagents and a great deal of
attention has been devoted to their versatile applications.
This class of compounds cannot be readily prepared by mixing up the tri-
methylsilyl chloride and the pseudohalides salts. The well-established method
for the synthesis of this class of compounds was based on the reaction between
[5]
the alkylsilyl chlorides and their corresponding silver salts. However, the
silver salts are expensive and not commonly available, and a high reaction
temperature was always required. Although the method for preparing trimethyl-
silyl cyanides using potassium salts impregnated on the amberlite XAD resin
[
6]
gave excellent yields, the preprocessing of the impregnation of the salts on
the expensive resin is troublesome. An alternative method reported for the prep-
aration of trimethylsilyl cyanide and isothiocyanate involved the interaction
between bis[trimethylsilyl] sulfate and urea with the expensive N-methylpyrro-
[
7]
lidinone as solvent. As far as those drawbacks concerned, some other cheaper
and more available pseudohalides sources, such as their potassium or sodium
salts, and mild reaction conditions should be more preferable.
Polyethylene glycols (PEGs) can be regarded as the open-chained crown
ether and have been used as solvation promoter or phase transfer catalyst
(PTC) in many organic reactions owing to their stability, low cost, environ-
mental friendliness, and easy availability.
[
8,9]
In many cases, they are good
substitutes for the traditional PTCs, such as the crown ether, which is toxic
and expensive, and quaternary ammonium salts or quaternary phosphonium
compounds, which are predominantly used in the liquid–liquid two-phase
reaction. In contrast with crown ethers, they have a more powerful ability to
solubilize the inorganic salts in nonpolar organic solvent because they have
two terminal polar hydroxyl groups. For example, it has been reported that
1
00 ml of PEG400 could dissolve 10 g of potassium thioacetate at room
[10]
temperature. For the sake of these merits of PEG, we came to study the
synthesis of trialkylsilyl pseudohalides by the phase-transfer catalyst
PEG400. Because water is not permitted to be involved in the reaction
system (because both trialkylsilyl chlorides and the trialkylsilyl pseudohalides
are sensitive to water), we envisage that the catalytic amount of PEG400
should first play the role of water to promote the solvolytic dissociation of
the inorganic salts by attacking its crystal lattice and should second act as
PTC to enhance the reaction rate.
We selected trimethylsilyl chloride and potassium cyanide as the starting
material to synthesize trimethylsilyl cyanide in dichloromethane in presence of
PEG400 under stirring at room temperature to study the general method for the
preparation of this class of compounds. However, only 40% of trimethylsilyl

Synthesis of Trimethylsilyl Pseudohalides
1273
cyanide was obtained after the mixture was stirred for 24 h when 5% mol of
PEG400 was dosed and 10% of potassium cyanide was overdosed based on tri-
methylsilyl chloride. Then, we thought about adding some Lewis acid to
enhance the reaction rate. Several Lewis acids were used and the comparative
experiments showed that zinc iodide exhibited the best catalytic effeciency,
from which we deduced that the participation of the iodine anion might play
a role by enhancing the rate of SN2 (Substitution Nucleophilic Bimolecular)
substitution. Seventy-five percent of trimethylsilyl cyanide was achieved
after the reaction was performed for 20 h with the introduction of 0.5% of
ZnI , which indicated that the introduction of the catalytic amount of ZnI
2
2
could greatly enhance the reaction rate and the product yield (Scheme 1).
However, the reaction time was still much longer than expected. It should
be pointed out that as the reaction proceeded, the trialkylsilyl chlorides
would react with the one or two terminal hydroxyl groups of PEG400 to
give the PEG400-silyated ether. The longer the reaction time, the more
PEG400 was silyated. Although the formed PEG400-silyated ether still
possessed the phase-transfer ability because it is also an analogue of acyclic
ether, its ability of dissociating the inorganic salts to give the negative nucleo-
phile must decrease with the loss of the hydroxyl groups.
It was reported in the previous literature that the ultrasonic irradiation
could play the role of promoting the solvolytic dissociation of the inorganic
[
11]
salts by attacking its crystal lattice. Based on this theory, we also introduce
the ultrasound irradiation into the experiment to promote the dissociation of
the salts of pseudohalides. As a result, the reaction time was greatly
enhanced compared with the experiment under stirring. The other two tri-
methylsilyl pseuodohalides, trimethylsilyl isothiocynate and trimethylsilyl
isocyante, were also prepared in the similar manner. The results are summa-
rized in Table 1.
The readilyavailable and recoverable dichloromethane was used as solvent
and the reaction was performed under ultrasound irradiaton in the presence of
catalytic amounts of PEG400 and zinc iodide. An excess (20%) of dried and
powdered inorganic pseudohalide salts was used for ensuring the complete con-
version of the reactants. The comparative experiments showed that the lower
dosage of PEG400 could not catalyze the reaction effectively, so an appropriate
amount of PEG400 (5% mol) is necessary to ensure better catalytic ability.
It can be shown from Table 1 that the presence of a catalytic amount of
Lewis acid obviously enhanced the reaction rate and improved the overall
yield. This might be explained by the fact that Lewis acid could enhance
Scheme 1.

1274
W. Sufang, W. Shaobing, and X. Yongshen
Table 1. Nucleophilic substitution of trimethylsilyl pseudohalides in CH Cl
2
2
a
catalyzed by PEG400 and Lewis acid under ultrasound irradiation
b
Entry
Salt
Product
(CH SiCN
Catalyst
Time (h)
Yield (%)
1
2
3
4
5
NaCN
NaCN
NaCN
NaCN
NaCN
NaCN
NaOCN
KSCN
3
)
3
none
AlCl3
20
7
15
48
45
46
80
78
85
86
(CH ) SiCN
3
3
3
3
3
3
(CH
(CH
)
)
SiCN
SiCN
ZnCl
ZnBr
ZnI2
2
7
2
6
(CH ) SiCN
3
4
3
c
6
(CH
(CH
(CH ) SiNCS
3
)
3
SiCN
ZnI
ZnI
2
2
16
3.5
5
7
8
3 3
) SiNCO
ZnI2
3
3
a
All the experiments were performed in a hood with good ventilation.
b
Yield of isolated products is calculated according to trialkylsilyl chlorides.
The reaction was performed under stirring for comparison purpose.
c
the break up of the Si–Cl bond and thus make it easier for the nucleophine to
attack the positive polarized Si. However, the catalytic effects of the different
Lewis acid vary under the same condition. Among the three Lewis acids, zinc
iodide showed the best catalytic ability, which might be explained by the fact
that iodide anion always showed excellent catalytic effect in an SN2 reaction.
CH Cl is an ideal solvent for the reaction in that it is miscible with
2
2
PEG400, recyclable, and has a boiling point much lower than that of the
product, which can ensure an effective separation. It is worthy of note that tri-
methylsilyl azide, although belonging to this class of compoud, should not be
prepared by this method because the inorganic azide salts are prone to explode
under ultrasound irradiation.
In a comparative experiment concerning the reaction between trimethyl-
silyl chloride with sodium cyanide, it was found that the reaction under
catalysis of metal iodide and ultrasound irradiation without PEG400 did not
take place. From this, a conclusion can be drawn that both PEG400 and
metal iodide play important roles in the conversion of the reaction; the import-
ance of the former is primary and the utilization of the ultrasound irradiation
could greatly shorten the reaction time.
In conclusion, we have found a convenient method for the preparation of
trimethylsilyl pseudohalides catalyzed by PEG400/ZnI under ultrasound
2
irradiation with the advantages of cheaper and more readily available
reagents, recoverability of the solvent, and the simplicity of the workup.
EXPERIMENTAL
GC: GC-17A with 2 m of column silicon-SE-30. A national ultrasound
cleanser operating at 40 MHz was used. TMSCl was freshly distilled.

Synthesis of Trimethylsilyl Pseudohalides
1275
Potassium cyanide was finely grounded and dried at 1208C under vacuum for
h. PEG400 and zinc iodide are commercially available and used directly
without further disposal.
6
Procedure for the Preparation of TMSNCS
A 100 ml, three-necked, round-bottomed flask equipped with nitrogen inlet
tube was charged successively with 0.5 g of ZnI , 30 ml of CH Cl , 2 g
2
2
2
(
(
0.005 mol) of PEG400, 7.8 g (0.12 mol) of potassium thiocyanide, and 12 g
0.11 mol) of TMSCl. The mixture was partly immersed into the ultrasound
cleanser thermostated at 208C for the period of time designated in Table.1
The process of the reaction was monitored by GC. After the completion of
the reaction, the inorganic solids were filtered off and washed with small
amount of dried CH Cl . After dichloromethane was distilled through a
2
2
[5]
5
-cm Vigreux column, 8.5 g of TMSCN was collected at 142–1448C (lit.
bp 143–1448C). Yield, 86%; purity by GC, 99.5%; IR (KBr, g cm ): 435,
21
6
34, 764, 845, 956, 1257, 1952, 2072, 2964. EI-MS (m/z): 132, 131, 116,
8, 86, 73, 43.
8
TMSNCO was prepared in the same fashion as described for TMSNCS.
[5]
Bp 90–938C (lit. bp 90–928C); yield, 86%; purity by GC, 98.5%; IR (KBr,
g cm ): 525, 620, 645, 761, 850, 1258, 1432, 2281, 2965, 3698. EI-MS
2
1
(
m/z): 115, 100, 72, 70, 43.
TMSCN was prepared in the same fashion as described for TMSNCS. Bp
[5]
1
15–1178C. (lit. bp 114–1178C); yield, 78%; purity by GC, 99.5%; IR
21
(
KBr, g cm ): 640, 770, 855, 1260, 1420, 2190, 2905, 2970. EI-MS (m/z):
9, 84, 73, 54, 43.
9
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