Russian Journal of Applied Chemistry, 2009, Vol. 82, No. 10, pp. 1776−1779.
Pleiades Publishing, Ltd., 2009.
Original Russian Text
L.T. Eremenko, D.A. Nesterenko, V.A. Garanin, V.P. Kosilko, 2009, published in Zhurnal Prikladnoi Khimii, 2009, Vol. 82, No. 10,
STUDIES IN THE FIELD OF CHEMISTRY OF NITRO COMPOUNDS
(TO 100TH BIRTHDAY ANNIVERSARY OF S. S. NOVIKOV)
Development of Improved Laboratory Technique
for Nicorandil Synthesis
L. T. Eremenko, D. A. Nesterenko, V. A. Garanin, and V. P. Kosilko
Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow oblast, Russia
Received April 29, 2009
Abstract—Results of a study of a two-stage laboratory technique for nicorandil synthesis from nicotinic acid
ethyl ester are presented. The process for nicorandil synthesis is fundamentally improved.
The research team headed by S.S. Novikov, for the
most part aimed to solve applied problems, has devoted
a considerable attention to synthesis and analysis of
properties of nitrates of organic polyfunctional alcohols.
Historically, nitrates are double-purpose compounds.
For example, manufacture of nitroglycerine is known to
specialists as a basis for development of dynamites and
powders. At the same time, nitroglycerine is a means for
curing heart pains. Nicorandil, a compound containing
a nitrate group, is presently regarded as the most effective
basis of anti-stenocardia medicinal preparations.
According to published evidence, nicorandil was ﬁ rst
obtained in Japan in 1976. Several patents for nicorandil
synthesis were issued in other countries [1–5]. Also
known are later publications about nicorandil synthesis in
China , Poland , Romania , India , and other
countries. Nicorandil is not manufactured in Russia.
The total number of publications devoted to nicorandil
has exceeded a thousand, whereas the chemistry and
synthesis technology of this compound have been
reflected in not more than one-and-a-half tens of
communications. For the most part, these are the already
mentioned patents and published data with a minimum
amount of technological information. At the same time,
analysis of these data reveals a number of shortcomings
in the existing technological processes for nicorandil
We used as the starting product for synthesis the
industrially manufactured ethyl nicotinate (I), which
reacts with 2-amino alcohol to give N-(2-hydroxyethyl)ni
cotinamide (II). Nitration of II yields the target nicorandil
(III) (see the Scheme).
The scheme is not novel. However, the above analysis
of published data suggests several improvements of the
laboratory technique for nicorandil synthesis. The aim of
our study was the following.
(i) To improve the stage in which II is obtained from
I with the excess components regenerated.
(ii) To modify the process of nitration of I to exclude
detonable combinations of the components.