Organic Preparations and Procedures International, 43:297–301, 2011
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2011.582002
Facile Carbethoxylation and Carbamoylation
of Ketones
Pavel Pazdera and Jan Simbera
Centre for Syntheses at Sustainable Conditions and their Management, Masaryk
University, Faculty of Science, Department of Chemistry, Kotlarska 2, Brno,
Czech Republic
α-Carbalkoxy and α-carboxamido derivatives of ketones are important compounds for the
pharmaceutical and fine chemical fields and have been prepared by the carbalkoxylation
and carbamoylation of enamines or of enolate ions generated by treatment of ketones
with strong base such as LDA, sodium, potassium, lithium hydrides, Grignard reagents
1
–4
5,6
7
etc, followed by alkoxycarbonylation with dialkyl oxalates or carbonates typicaly in
2
,3,8
benzene or tetrahydrofuran at low temperatures and under inert atmosphere.
There is
still a compelling need to develop novel methods which would lead to higher yields of
functional derivatives of 2-oxocarboxylic in shorter times and under milder conditions with
simple work-up procedures.
The sonochemical phase-transfer-catalysis (PTC) under solid-liquid (S-L PTC) and
liquid-liquid conditions (L-L PTC) is a very important and effective method to accomplish
such purpose. Moreover L-L PTC is generally known to be very useful for the deprotona-
9
10
tion of different H-X systems. Synergism between PTC and ultrasound is also known.
Ultrasound irradiation has been shown to be a clean and valuable approach in organic syn-
thesis over the last three decades and more convenient in comparison with the traditional
1
–8
methods.
For these reasons, it was assumed that the generation of enolate anions from ketones
by the synergic effect of ultrasound and S-L PTC should be comparable with the action of
strong bases. A further advantage of S-L PTC over L-L PTC reactions is the fact that the
use of highly concentrated aqueous alkaline hydroxide solutions (ca. 40%) that can lead
also to competitive condensation reactions of the ketones, is avoided.
We performed the acylation of cyclic ketones 1 with variable ring size and on the
acyclic ketones 3 with ethyl chloroformate and the results show that this method may be
used for variety of ketones (Scheme 1). It is also evident that increasing alkylation at the α-
carbon decreases the acidity of remaining α-hydrogen and the tendency toward enolization
Submitted November 15, 2010.
Address correspondence to Pavel Pazdera, Centre for Syntheses at Sustainable Conditions and
their Management, Masaryk University, Faculty of Science, Department of Chemistry, Kotlarska 2,
CZ-61137 Brno, Czech Republic. E-mail: pazdera@chemi.muni.cz
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