Tetrahedron Letters
A convenient one-pot synthesis of ketone cyanohydrin esters
in aqueous media
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Sirawit Wet-osot, Mookda Pattarawarapan, Wong Phakhodee
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient one-pot, two-step procedure for the synthesis of ketone cyanohydrin esters in aqueous
media is reported using N-acylbenzotriazoles as the acylating agents. In saturated aqueous sodium
bicarbonate containing a catalytic amount of tetrabutylammonium bromide, the reaction of ketones with
potassium cyanide and N-acylbenzotriazoles proceeded readily at room temperature to provide the
corresponding O-acyl cyanohydrin derivatives in good to excellent yields.
Received 12 October 2015
Revised 9 November 2015
Accepted 11 November 2015
Available online 12 November 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
N-Acylbenzotriazoles
Cyanohydrin
Ketones
Aqueous
Phase transfer catalyst
Introduction
number of organic transformations.9 Unlike acid chlorides which
are difficult to isolate, relatively unstable, and sensitive to mois-
Cyanohydrin esters are important synthetic building blocks
which exhibit a wide range of applications in fine chemical, phar-
maceutical, and agrochemical industries.1 Based on their synthetic
value, a number of methods have been developed for their prepa-
ration, including acylation of cyanohydrins or O-trimethylsilyl
cyanohydrins with acyl halides (or acid anhydrides),2 cyanoacyla-
tion of carbonyl compounds using cyanating agents such as metal
cyanides,3 trimethylsilyl cyanide,4 or potassium hexacyanoferrate
(II),5 the reaction of aldehydes (or ketones) with acyl cyanides,6
as well as the reductive coupling of acyl cyanides in the presence
of sodium borohydride7 or trimethylphosphine.8 Nevertheless,
many of these methods involve the use of expensive reagents in
excess amounts, harsh conditions, extended reaction times, or
the generation of toxic metallic wastes. In addition, commercially
available cyanohydrins or acyl cyanides are limited in number
and relatively expensive. In fact, most reported examples of O-acyl
cyanohydrins have been restricted to acetate and benzoate deriva-
tives of aldehyde substrates. Thus, it is still desirable to develop a
simple and effective protocol for the preparation of more struc-
turally diverse cyanohydrin esters of ketones using inexpensive
and readily available reagents.
ture, benzotriazole derivatives are stable solids which can be read-
ily prepared and kept at room temperature for long periods of time
without decomposition. Moreover, due to their stability, they can
be used in the presence of water which is well suited for reactions
with water-soluble nucleophiles.10 Although benzotriazole
derivatives have been applied in a variety of N-acylation reactions
such as in the synthesis of amides,10b,11 peptides,10c–e,12 and acyl
azides,10a,13 to the best of our knowledge, their application in the
synthesis of cyanohydrin esters has not been reported.
In
a continuation of our interest on the synthesis and
applications of N-AcBt,14 we report herein a mild and effective pro-
tocol toward O-acyl cyanohydrins proceeding through a one-pot
two-step reaction of ketones with potassium cyanide, followed
by acylation with N-AcBt in aqueous media.
Results and discussion
The preparation of ketone cyanohydrins from ketones and HCN
has been proven to be difficult due to the thermodynamic instabil-
ity of the products.15 As a consequence, these derivatives are
commonly synthesized in their O-protected form as trialkylsilyl-
protected cyanohydrins.16 The formation of ketone cyanohydrin
esters using this synthetic route would require an additional
deprotection step prior to acylation making the method more
complicated and impractical.
N-Acylbenzotriazoles (N-AcBt) are neutral acylating agents
which have been applied as a substitute for acid chlorides in a
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0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.