Synthesis of diaryl-substituted 3,4-dimethyl-2-oxo-1,2,3,6- tetrahydropyrimidine-5-carboxamides

Full text of DOI:10.1134/S1070363213040324

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 4, pp. 781–782. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © V.L. Gein, A.Yu. Fedotov, T.M. Zamaraeva, M.I. Vakhrin, 2013, published in Zhurnal Obshchei Khimii, 2013, Vol. 83, No. 4,
pp. 701–702.
LETTERS
TO THE EDITOR
Synthesis of Diaryl-Substituted 3,4-Dimethyl-2-oxo-1,2,3,6-
tetrahydropyrimidine-5-carboxamides
V. L. Gein, A. Yu. Fedotov, T. M. Zamaraeva, and M. I. Vakhrin
Perm State Pharmaceutical Academy, ul. Polevaya 2, Perm, 614990 Russia
e-mail: geinvl48@mail.ru
Received November 28, 2012
DOI: 10.1134/S1070363213040324
The multicomponent reactions, in particular
Biginelli reaction, are commonly used to construct the
heterocyclic systems as the preparation method of a
broad range of compounds containing the pyrimidine
ring [1, 2].
amides I–V. The reaction occurs at 120–150°C in the
solvent-free conditions within 10–15 min.
Compounds I–V are colorless crystalline
substances, which are soluble in DMF, DMSO,
chloroform, and ethanol (under heating), insoluble in
water.
In the 1H NMR spectra of compounds I–V,
alongside the signals of aromatic protons and groups
attached to the aromatic ring, there are two singlets at
3.05–3.10 and 1.91–2.27 ppm belonging to the CH3
groups, the doublets of С6Н proton at 5.22–5.64 ppm,
and of the N1H proton at 7.60–7.96 ppm (J1,6 2.95–
3.33 Hz), the singlet of the amide protons in the range
of 9.02–9.43 ppm. The splitting of signals of the H1,6
protons of the pyrimidine ring indicates that the
Previously we have shown that the N-aryl-
substituted 6-aryl-4-methyl-2-oxo-1,2,3,6-tetrahydro-
pyrimidine-5-carboxamides were formed in the reac-
tion of acetylacetic acid N-arylamides with aromatic
aldehyde and urea [3].
Continuing study in this area, we carried out a
three-component condensation of N-2-methyl(chloro)-
acetoacetanilides with N-methylurea and aromatic
aldehydes to obtain the diaryl-substituted 3,4-di-
methyl-2-oxo-1,2,3,6-tetrahydropyrimidine-5-carbox-
R1
O
CH3
N
H
N
N
H
O
R1
R2
O
O
O
O
H
A
CH3
+
+
H2N
N
N
R1
H
H
R2
O
N
H
NH
N
O
R2
CH3
B
I_V
R1 = Me, R2 = H (I), R1 = Me, R2 = 2-Cl (II), R1 = Cl, R2 = H (III), R1 = Cl, R2 = 3-NO2 (IV), R1 = Cl, R2 = 2-Cl (V).
781

782
GEIN et al.
reaction proceeds regioselectively, and the structure B
is not formed.
197°C. 1Н NMR spectrum, δН, ppm: 2.26 s (3Н, С4Н3),
3.05 s (3Н, С3Н3), 5.22 d (1Н, СН, J1,6 3.20 Hz), 7.43
m (9H, Ar), 7.62 d (1Н, N1H, J1,6 3.20 Hz), 9.04 s (1Н,
NHamide). Found, %: С 63.96, 64.26; Н 5.02, 5.17; N
11.70, 11.91. C19H18ClN3O2. Calculated, %: С 64.14;
Н 5.10; N 11.81.
The mass spectrum of compound IV contains a
molecular ion peak at m/z 400 [М]+ and the peaks of
fragment ions at m/z 274 [M – ClC6H4NH]+ and 153
[M – ClC6H4NH – C6H4NO2]+. In the mass spectrum of
V there are the molecular ion peak at m/z 391 [М]+ and
the peaks of fragment ions at m/z 266 [M –
ClC6H4NHСО – C6H4Сl]+ and 77 [Ph]+ (m/z 77), which
confirm the assumed structure.
3,4-Dimethyl-6-(3-nitrophenyl)-N-2-chloro-
phenyl-2-oxo-1,2,3,6-tetrahydropyrimidine-5-carbox-
amide (IV) was prepared similarly. Yield 3.24 g (81%),
1
mp 184–186°C. Н NMR spectrum, δН, ppm: 2.27 s
(3Н, С4Н3), 3.10 s (3Н, С3Н3), 5.41 d (1Н, СН, J1,6
3.33 Hz), 7.85 m (8H, Ar), 7.96 d (1Н, N1H, J1,6
3.33 Hz), 9.43 s (1Н, NHamide). Found, %: С 56.80,
57.09; Н 4.22, 4.37; N 13.88, 14.07. C19H17ClN4O4.
Calculated, %: С 56.94; Н 4.28; N 13.98.
3,4-Dimethyl-N-(2-methylphenyl)-6-phenyl-2-oxo-
1,2,3,6-tetrahydropyrimidine-5-carboxamide (I). A
mixture of 0.01 mol of 2-methylacetoacetanilide,
0.01 mol of benzaldehyde, and 0.01 mol of N-methylurea
was heated at 120–150°C for 10–15 min until the gas
evolution completed and the reaction mixture
solidified. After cooling, the residue was treated with
ethanol, filtered off, and recrystallized from ethanol.
Yield 2.24 g (67%), mp 210–212°C. 1Н NMR
spectrum, δН, ppm: 1.94 s (3Н, С4Н3), 2.21 s (3Н,
CH3C6H4), 3.05 s (3Н, С3Н3), 5.24 d (1Н, СН, J1,6 2.95
Hz), 7.61 m (9H, Ar), 7.64 d (1Н, N1H, J1,6 2.95 Hz),
9.31 s (1Н, NHamide). Found, %: С 71.73, 71.51; Н
6.23, 6.39; N 12.43, 12.63. C20H21N3O2. Calculated,
%: С 71.62; Н 6.31; N 12.53.
4-(2-Chlorophenyl)-1,6-dimethyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylic acid N-(2-
chlorophenyl)amide (V) was obtained similarly.
1
Yield 2.44 g (69%), mp 203–205°C. Н NMR spec-
trum, δН, ppm: 2.26 s (3Н, С4Н3), 3.08 s (3Н, С3Н3),
5.62 d (1Н, СН, J1,6 3.19 Hz), 7.40 m (8H, Ar), 7.65 d
(1Н, N1H, J1,6 3.19 Hz), 9.40 s (1Н, NHamide). Found,
%: С 58.39, 58.61; Н 4.33, 4.47; N 10.68, 10.89.
C19H17Cl2N3O2. Calculated, %: С 58.48; Н 4.39; N
10.77.
1
The H NMR spectra were recorded on a Bruker
3,4-Dimethyl-N-(2-methylphenyl)-6-(2-chloro-
phenyl)-2-oxo-1,2,3,6-tetrahydropyrimidine-5-carbox-
amide (II) was prepared similarly. Yield 2.66 g (72%),
500 (500.13 MHz) spectrometer in DMSO-d6, internal
reference TMS. The mass spectra were obtained on a
Finnigan MAT INCOS-50 instrument with ionization
energy of 70 eV.
1
mp 192–194°C. Н NMR spectrum, δН, ppm: 1.91 s
(3Н, С4Н3), 2.23 s (3Н, CH3C6H4), 3.09 s (3Н, С3Н3),
5.64 d (1Н, СН, J1,6 2.95 Hz), 7.35 m (8H, Ar), 7.60 d
(1Н, N1H, J1,6 2.95 Hz), 9.02 s (1Н, NHamide). Found,
%: С 64.85, 65.06; Н 5.38, 5.52; N 11.27, 11.48.
C20H20ClN3O2. Calculated, %: С 64.95; Н 5.45; N
11.36.
REFERENCES
1. Vdovina, S.V. and Mamedov, V.A., Usp. Khim., 2008,
vol. 77, no. 12, p. 1091.
2. Kappe, C.O., Multicomponent Reactions, 2005, p. 95.
3,4-Dimethyl-N-2-chlorophenyl-6-phenyl-2-oxo-
1,2,3,6-tetrahydropyrimidine-5-carboxamide (III)
was prepared similarly. Yield 2.77 g (78%), mp 195–
3. Gein, V.L., Zamaraeva, T.M., Kurbatova, A.A., and
Vakhrin, M.I., Khim. Geterotsikl. Soed., 2010, no. 7,
p. 1058.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 4 2013