An improved synthesis of cyanohydrins in the presence of solid LiClO4 under solvent-free conditions

Article abstract of DOI:10.1016/j.jorganchem.2003.09.014

Several cyanohydrins were synthesized by the reaction of trimethylsilyl cyanide with carbonyl compounds in the presence of solid lithium perchlorate in high yields under solvent-free conditions.

Full text of DOI:10.1016/j.jorganchem.2003.09.014

Journal of Organometallic Chemistry 688 (2003) 283Á285
/
www.elsevier.com/locate/jorganchem
An improved synthesis of cyanohydrins in the presence of solid
LiClO under solvent-free conditions
4
Najmedin Azizi, Mohammad R. Saidi *
Department of Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran
Received 16 July 2003; received in revised form 2 September 2003; accepted 3 September 2003
Abstract
Several cyanohydrins were synthesized by the reaction of trimethylsilyl cyanide with carbonyl compounds in the presence of solid
lithium perchlorate in high yields under solvent-free conditions.
#
2003 Published by Elsevier B.V.
Keywords: Cyanohydrin; Lithium perchlorate; Solvent-free, Trimethylsilyl cyanide
1
. Introduction
procedure and a need for relatively expensive reagents
such as titanium complexes and Schiff bases. All of the
reactions have been carried out in solvents such as
CH Cl , CH CN, THF, etc. On the other hand, due to
The cyanation reaction of carbonyl compounds is one
of the most powerful procedures for the synthesis of
poly-functional molecules [1]. Cyanohydrins or cyano-
hydrin trimethylsilyl ethers, can easily be converted to a-
hydroxycarboxylic acids [2], a-hydroxyaldehydes [3], b-
aminoalcoholes [4], a-amino acid derivatives [5]. In
addition, they also have been used for the synthesis of
insecticides [6], ferroelectrics, and liquid crystals [7,8].
Several useful cyanating reagents have been reported in
the literature [9]. Among them, trimethylsilylcyanide
2
2
3
the current challenges for developing solvent-free and
environmentally benign synthetic systems [15] and in
continuation with our interests on the applications of
lithium perchlorate for various organic transformations
[16], we would like to report a novel method for the
cyanation of carbonyl compounds with TMSCN in the
presence of solid LiClO under solvent-free conditions.
4
When an aldehyde or a ketones was allowed to react
with TMSCN in the presence of catalytic amounts of
solid lithium perchlorate, the cyanation of the carbonyl
compounds proceed effectively to give the correspond-
ing cyanohydrins in good yields, Scheme 1.
The structures of the cyanohydrins are shown in
Tables 1 and 2. Benzaldehyde was chosen to optimize
the reaction conditions, such as temperature, time, and
(
TMSCN) seems to be one of the most effective and safe
cyanating sources for nucleophilic addition to carbonyl
compounds. Generally TMSCN reacts with a carbonyl
compound in the presence of a catalyst. Many different
catalysts have been developed for this reaction [9]. Lewis
acids and some other additives, both in stoichiometric
and catalytic amounts have been used as promoting
agents for cyanating of carbonyl compounds [10]. In
recent years, several optically active catalysts for asym-
metric synthesis of cyanohydrins have also been re-
molar ratio of solid LiClO to substrate. We found that
4
one equivalent of solid LiClO was sufficient to obtain
4
the desired cyanohydrins in excellent yield and after
short reaction times. The reaction with both aldehydes
and ketones afforded the corresponding cyanohydrins in
excellent yields. Tables 1 and 2 clearly show that
aliphatic and aromatic aldehydes with electron-donating
and withdrawing groups gave excellent yields of cyano-
hydrins. The nature of the substituent on the aromatic
ring seems to have no major effect on the reaction rate.
ported in the literature [11Á14].
Unfortunately, many of these procedures often re-
quire drastic reaction conditions with a tedious work up
/
*
Corresponding author. Tel.: ꢀ
983.
E-mail address: saidi@sharif.edu (M.R. Saidi).
/
98-21-600-5718; fax: ꢀ98-21-601-
/
2
0
022-328X/03/$ - see front matter # 2003 Published by Elsevier B.V.

284
N. Azizi, M.R. Saidi / Journal of Organometallic Chemistry 688 (2003) 283Á285
/
Table 2
4
Addition of TMSCN to ketones mediated by LiClO under solvent-
free conditions
Scheme 1.
Table 1
4
Addition of TMSCN to aldehydes mediated by LiClO under solvent-
free conditions
products were characterized by comparison of their
spectral data (GC, IR, NMR) with authentic sample or
with those reported in the literature.
2. Conclusion
In conclusion solid lithium perchlorate is found to be
a mild and efficient Lewis acid for promoting cyanosi-
lylation of carbonyl compounds under neutral condi-
tions. The availability of inexpensive starting materials
together with simplicity of the reaction, and green
methodology provide a convenient method for the
preparation of cyanohydrins in high yields and after
short reaction times.
3. Experimental
3.1. General procedure
A mixture of a carbonyl compound (2 mmol), solid
LiClO (2 mmol) and TMSCN (2.4 mmol) was stirred at
Furthermore, acid sensitive aldehydes such as furfur-
aldehyde and cinnamaldehyde worked well without any
decomposition or polymerization under the reaction
conditions. In the case of aliphatic aldehydes, one also
observes quantitative yield after short reaction times.
Aliphatic and aromatic ketons, such as acetone, acet-
ophenone, cyclohexanone, cyclopentanone and benzo-
phenone, also gave the corresponding cyanohydrins in
good yields, although addition of TMSCN to ketones
are slower in comparison with aldehydes, Table 2. All
4
room temperature (r.t.) for the time indicated in Tables
1
and 2. Then CH Cl was added to the reaction mixture
2 2
and the lithium perchlorate was filtered off. The organic
layer was washed with water, dried over anhydrous
Na SO . Solvent was removed by a rotary evaporator
2
4
and almost pure crude product was obtained. Further
purification was done by flash chromatography (petro-
leum ether, diethyl ether) to afford the pure cyanohy-
drins.

N. Azizi, M.R. Saidi / Journal of Organometallic Chemistry 688 (2003) 283Á
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285
[
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We are grateful to the Sharif University of Technol-
ogy Research Council for financial support of this
research. We also thank ‘Volkswagen-Stiftung, Federal
Republic of Germany’ for financial support towards the
purchase of equipments and chemicals.
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