Russian Journal of Organic Chemistry, Vol. 41, No. 1, 2005, pp. 95 -97. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005,
pp. 97-98.
Original Russian Text Copyright Ó 2005 by Bratenko, Chornous, Vovk.
4-Functionally Substituted 3-Heterylpyrazoles:
XIII.* 3-Aryl(heteryl)-4-(4-pyrazolyl)-1,2,3,4-tetrahydro-
pyrimidin-2-ones(thiones)
M. K. Bratenko1, V. A. Chornous1, and M. V. Vovk2
1 Bukovina State Medical Academy, Teatralnaya pl. 2, Chernovtsy, 58000 Ukraine
2 Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received October 29, 2004
AbstractCyclocondesation of 3-aryl(heteryl)pyrazole-4-carbaldehydes with ethyl acetoacetate and urea
(thiourea) in the presence of FeCl3 ·6H2O afforded 3-aryl(heteryl)-4-(4-pyrazolyl)-1,2,3,4-tetrahydropyrimidin-2-
ones(thiones).
Some 1,2,3,4-tetrahydropyrimidin-2-one derivatives
were found to exhibit pronounced hypotensive activity
and negative inotropic effect [25]. The simplest and most
convenient approach to such compounds is based on the
Biginelli reaction which implies one-step three-component
condensation of aromatic or aliphatic aldehydes, b-keto
esters, and urea under strongly acidic conditions. This
reaction leads to formation of the corresponding alkyl
4-aryl(alkyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
pyrimidine-5-carboxylates [6]. Among heterocyclic
aldehydes, only thiophene-2-carbaldehyde was involved
in such condensations [7, 8].
Scheme 1.
&+ 2
1
2
2
5
0H
2(W
1
3K
,D ,H
+
1
0H
;
;
)H&O ꢀꢀꢁ+ 2
1+
(W22&
5
+ 1
1+
,,Dꢀꢁ,,E
The present communication describes the results of
our studies on the synthesis of new 1,2,3,4-tetra-
hydropyrimidin-2-one derivatives having pyrazolyl
substituents in position 4 of the pyrimidine ring. Our
attempts to isolate condensation products in reactions of
3-aryl(heteryl)pyrazole-4-carbaldehydes IaIe with ethyl
acetoacetate and urea in the presence of a catalytic
amount of concentrated hydrochloric acid were
unsuccessful. On the other hand, pyrazole-4-carb-
aldehydes were used previously to build up bicyclic
ensembles consisting of pyrazole and 1,4-dihydropyridine
[9] or dihydropyrazole rings [10].
1
1
3K
,,,D ,,,J
I, R = Ph (a), 4-ClC6H4 (b), 4-MeC6H4 (c), 4-MeOC6H4 (d),
2-thienyl (e); II, X = O (a), S (b); III, X = O, R = Ph (a),
4-ClC6H4 (b), 4-MeC6H4 (c), 4-MeOC6H4 (d), 2-thienyl (e);
X = S, R = Ph (f), 4-ClC6H4 (g).
urea (IIa) or thiourea (IIb), and FeCl3 · 6 H2O at a ratio
of 1:1:2:0.6 in boiling ethanol for 3 h we obtained ethyl
3-aryl(heteryl)-2-oxo-4-(4-pyrazolyl)-1,2,3,4-tetrahydro-
pyrimidine-5-carboxylates IIIaIIIe and their 2-thioxo
analogs IIIf and IIIg in 5266% yield (Scheme 1).
Taking into account recently reported data [11] on the
use of iron(III) chloride hexahydrate as catalyst in the
Biginelli reaction, we tried to apply an analogous
procedure to the syntheses with aldehydes I. In fact, by
heating a mixture of aldehyde IaIe, ethyl acetoacetate,
Compounds IIIaIIIg (Tables 1, 2) are colorless high-
melting crystalline substances. Their IR spectra contain
strong absorption bands due to stretching vibrations of
the carbonyl groups in the pyrimidine ring (1675
1
* For communication XII, see [1].
1690 cm ) (compounds IIIaIIIe) and ester fragment
1070-4280/05/4101-0095Ó2005 Pleiades Publishing, Inc.