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ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 1, pp. 19–24. © Pleiades Publishing, Ltd., 2019.
Russian Text © A.M. Semenova, R.V. Oganesyan, V.V. Dotsenko, E.A. Chigorina, N.A. Aksenov, I.V. Aksenova, E.E. Netreba, 2019, published in Zhurnal
Obshchei Khimii, 2019, Vol. 89, No. 1, pp. 25–30.
Reaction of 5-Amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile
with Hydroxycyclohexanones
A. M. Semenovaa,b, R. V. Oganesyana, V. V. Dotsenkoa,c*,
E. A. Chigorinad, N. A. Aksenovc, I. V. Aksenovac, and E. E. Netrebae
a Kuban State University, ul. Stavropol’skaya 149, Krasnodar, 350040 Russia
*e-mail: victor_dotsenko_@mail.ru
b North Caucasian State Humanitarian and Technological Academy, Medical Institute, Cherkessk, Russia
c North Caucasus Federal University, Stavropol, Russia
d National Research Center “Kurchatov Institute” – IREA, Moscow, Russia
e Taurida Academy of V.I. Vernadsky Crimean Federal University, Simferopol, Russia
Received July 5, 2018; revised July 5, 2018; accepted July 13, 2018
Abstract—The reaction of 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile with 3-aryl-5-hydroxy-5-
methyl-2,4-di(ethoxycarbonyl)cyclohexanones in acetic acid furnished previously unknown 4,5,6,7,8,9-hexa-
hydropyrazolo[1,5-a]quinazoline derivatives.
Keywords: β-cycloketols, aminopyrazole, cyclocondensation, pyrazolo[1,5-a]quinazoline
DOI: 10.1134/S1070363219010043
Cyclic 1,3-dicarbonyl compounds 2,4-di[RC(O)]-3-
aryl-5-hydroxy-5-methylcyclohexanones 1 (β-cyclo-
ketols), available by the reaction of aromatic aldehydes
with acetoacetic ester, are prospective reagents for fine
organic synthesis. According to reviews [1, 2], β-
cycloketol can serve as a starting point for obtaining
substituted carbocycles, 2-oxabicyclo[2.2.2]octanes,
enaminoketones and -esters, etc. At the same time, it
should be noted that the data on heterocyclization
reactions with β-cycloketol are scarce. Thus, prepara-
tion of isoquinolines 2 [3–7], indazoles 3 [1, 8–10],
benzo[c]isoxazoles 4 [1, 9, 10], [1,2,4]triazolo[3,4-b]-
quinazolines 5 [11] and pyrazolo[3,4-c]isoquinolines 6
[12] via condensation reactions of cycloketols with
various 1,2- and 1,3-binucleophilic agents have been
reported (Scheme 1).
hydropyrazolo[5,1-b]quinazoline-9(5H)-one
7
[15]
(Scheme 1). It is worth noting that the analytical data
presented in [15] (mass spectrometry and IR spectro-
scopy) are obviously not enough to confirm the
structure of the claimed product.
Continuing research in the field of the chemistry of
malononitrile dimer derivatives [16–19] and condensa-
tion reactions based on 3(5)-aminopyrazoles [20, 21],
herein we reported the reaction of 3-aryl-5-hydroxy-5-
methyl-2,4-di(ethoxycarbonyl)cyclohexanones 1a, 1b
with 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbo-
nitrile 7 (Scheme 2). Aminopyrazole 7 is easily formed
by the reaction of malononitrile dimer 8 with
hydrazine hydrate [22] and, due to the presence of a
number of amino and cyano groups, can enter into
condensation reactions with the formation of
functional derivatives [23–25]. β-Ketoesters (and β-
cycloketols in particular) have not previously been
reacted with aminopyrazole 7. Due to the fact that the
probable products of the pyrazoloquinoxaline series
are of interest for pharmacology [26–28], the study of
this interaction seems promising.
The last two transformations are of particular interest,
because, despite the considerable attention paid to the
condensation reactions of aminoazoles with 1,3-
bioelectrophils (see [13, 14]), only some examples of
such reactions involving β-cycloketols were found. So,
we managed to find the only and recent mention of the
reaction of cycloketol with 5-amino-3-hydrazino-
pyrazole, leading to the formation of 6,7,8,8a-tetra-
We found that cycloketols 1a, 1b react with 5-
amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile
7
19