Synthesis of tetrahydropyrimidin-2-one derivatives from N-tert-butylurea

Full text of DOI:10.1134/S1070428008100321

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 10, pp. 1562–1563. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © M.M. Kurbanova, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 10, pp. 1583–1584.
SHORT
COMMUNICATIONS
Synthesis of Tetrahydropyrimidin-2-one Derivatives
from N-tert-Butylurea
M. M. Kurbanova
Baku State University, ul. Z. Khalilova 23, Baku, 1073 Azerbaidjan
e-mail: kurbanova1972@rambler.ru
Received October 6, 2007
DOI: 10.1134/S1070428008100321
It is known that some functionalized oxo deriva-
tives of pyrimidines exhibit a broad spectrum of biol-
ogical and pharmacological activity. Dihydropyrimi-
dine-5-carboxylate moiety is a structural fragment of
many natural marine products, in particular batzella-
dine alkaloids which inhibit HIV gp-120-CD4 [1]. In
addition, 4-aryldihydropyrimidinones are potent calci-
um channel blockers, antihypertensive agents, α1a-ad-
renergic antagonists, and neuropeptide antagonists [2].
The possibility of using pyrimidinone derivatives as
new class of calcium channel blockers has attracted
interest of many researchers.
yl-4-R-3,4-dihydropyrimidin-2(1H)-ones IV–VI in
~80% yield. The IR spectra of the condensation prod-
ucts contained strong absorption bands due to stretch-
ing vibrations of the C5=O carbonyl group at 1675–
1690 cm–1, ester carbonyl group in compounds I–III at
1745–1750 cm–1, and NH bond at 3375 cm–1.
General procedure for the synthesis of com-
pounds I–VI. A mixture of 25 mmol of the corre-
sponding aromatic aldehyde, 38 mmol of ethyl aceto-
acetate or acetylacetone, 5.8 g (0.05 mol) of N-tert-
butylurea, 25 mg of trichloroacetic acid, and 10 ml of
95% ethanol was stirred for 2–4 h at 78°C. The prog-
ress of the reaction was monitored following the dis-
appearance of organic substrate (ethyl acetoacetate or
acetylacetone) by TLC using Silufol UV-254 plates
(eluent ethyl acetate–hexane, 1:1). When the reaction
was complete, the mixture was cooled to room tem-
perature, and the precipitate was filtered off, washed
with ethanol, dried, and recrystallized from aqueous
ethanol.
Taking the above stated into account, one-pot syn-
thesis of some pyrimidinone derivatives in the pres-
ence of trichloroacetic acid was performed [3]. In
continuation of studies in this field, the present com-
munication reports on a new three-component conden-
sation of ethyl acetoacetate with N-tert-butylurea and
aromatic aldehydes, which leads to the formation of
ethyl 3-tert-butyl-6-methyl-2-oxo-4-R-1,2,3,4-tetrahy-
dropyrimidine-5-carboxylates I–III in 70% yield. The
condensation with another CH acid, acetylacetone,
gave analogous products, 5-acetyl-3-tert-butyl-6-meth-
Ethyl 3-tert-butyl-6-methyl-2-oxo-4-phenyl-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (I).
Yield 70%, mp 150–151°C. IR spectrum, ν, cm–1:
1
1255, 1680, 1745, 3350. H NMR spectrum, δ, ppm:
O
O
O
1.31 t (3H, CH3), 1.40 s (9H, t-Bu), 2.50 s (3H, CH3),
4.35 d (2H, CH2O), 4.70 s (1H, CH), 7.68–7.89 m
(5H, Harom), 8.78 s (1H, NH). Found %: C 68.44;
H 7.64; N 8.90. C18H24N2O3. Calculated, %: C 68.35;
H 7.59; N 8.86.
RCHO
+
+
Me
R'
H2N
N
NHBu-t
O
R
Bu-t
R'
Ethyl 3-tert-butyl-4-(2-hydroxyphenyl)-6-meth-
yl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carbox-
ylate (II). Yield 69%, mp 220–222°C. IR spectrum, ν,
Me
N
H
O
1
cm–1: 1250, 1675, 1740, 3330. H NMR spectrum, δ,
I–VI
ppm: 1.30 t (3H, CH3), 1.47 s (9H, t-Bu), 2.55 s (3H,
CH3), 4.30 d (2H, CH2O), 4.85 s (1H, CH), 7.25–
I, IV, R = Ph; II, V, R = 2-HOC6H4; III, VI, R = 2-HO-5-BrC6H3;
I–III, R′ = EtO; IV–VI, R′ = Me.
1562

SYNTHESIS OF TETRAHYDROPYRIMIDIN-2-ONE DERIVATIVES
1563
7.55 m (4H, Harom), 9.40 s (1H, NH), 10.0 s (1H, OH).
Found, %: C 65.09; H 7.17; N 8.50. C18H24N2O4. Cal-
culated, %: C 65.06; H 7.22; N 8.43.
(1H, OH). Found, %: C 67.46; H 7.32; N 9.28.
C17H22N2O3. Calculated, %: C 67.54; H 7.28; N 9.27.
5-Acetyl-4-(5-bromo-2-hydroxyphenyl)-3-tert-
butyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one
(VI). Yield 78%, mp 215–216°C. IR spectrum, ν, cm–1:
1680, 3335, 1245. 1H NMR spectrum, δ, ppm: 1.41 s
(9H, t-Bu), 2.21 s (3H, CH3), 2.57 s (3H, CH3), 4.70 s
(1H, CH), 7.00–7.58 m (3H, Harom), 8.60 s (1H, NH),
10.4 s (1H, OH). Found, %: C 53.46; H 5.42; Br 20.87;
N 7.29. C17H21BrN2O3. Calculated, %: C 53.54;
H 5.51; Br 20.99; N 7.34.
Ethyl 4-(5-bromo-2-hydroxyphenyl)-3-tert-butyl-
6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
boxylate (III). Yield 67%, mp 240–241°C. IR spec-
trum, ν, cm–1: 1250, 1675, 1740, 3330. 1H NMR spec-
trum, δ, ppm: 1.36 t (3H, CH3), 1.41 s (9H, t-Bu),
2.57 s (3H, CH3), 4.25 d (2H, CH2O), 4.70 s (1H, CH),
7.00–7.60 m (3H, Harom), 8.70 s (1H, NH), 10.4 s (1H,
OH). Found, %: C 52.60; H 5.65; Br 19.50; N 6.74.
C18H23BrN2O4. Calculated, %: C 52.55; H 5.59;
Br 19.46; N 6.81.
1
The H NMR spectra were recorded at 25°C on
a Bruker spectrometer (300 MHz) from solutions in
DMSO-d6. The IR spectra were measured in mineral
oil on a Specord 75IR instrument. The progress of re-
actions and the purity of products were monitored by
thin-layer chromatography.
5-Acetyl-3-tert-butyl-6-methyl-4-phenyl-3,4-di-
hydropyrimidin-2(1H)-one (IV). Yield 80%, mp 130–
132°C. IR spectrum, ν, cm–1: 1255, 1675, 3335.
1H NMR spectrum, δ, ppm: 1.40 s (9H, t-Bu), 2.21 s
(3H, CH3), 2.50 s (3H, CH3), 4.70 s (1H, CH), 7.68–
7.89 m (5H, Harom), 8.78 s (1H, NH). Found, %:
C 71.36; H 7.52; N 9.68. C17H22N2O2. Calculated, %:
C 71.32; H 7.69; N 9.79.
REFERENCES
1. Snider, B.B, Chen, J., Patil, A.D., and Freyer, A.,
Tetrahedron Lett., 1996, vol. 37, p. 6977.
2. Rovnyak, G.C., Atwal, K.S., Hedberg, A., Kimball, S.D.,
Moreland, S., Gougoutas, J.Z., Schwartz, J.,
O’Reilly, B.C., and Malley, M.F., J. Med. Chem., 1992,
vol. 35, p. 3254.
3. Magerramov, A.M., Kurbanova, M.M., Abdinbeko-
va, R.T., Rzaeva, I.A., Farzaliev, V.M., and Allakhver-
diev, M.A., Zh. Prikl. Khim., 2006, vol. 79, p. 796.
5-Acetyl-3-tert-butyl-4-(2-hydroxyphenyl)-6-
methyl-3,4-dihydropyrimidin-2(1H)-one (V). Yield
77%, mp 196–197°C. IR spectrum, ν, cm–1: 1680,
3335, 1245. H NMR spectrum, δ, ppm: 1.37 s (9H,
t-Bu), 2.20 s (3H, CH3), 2.55 s (3H, CH3), 4.85 s (1H,
1
CH), 7.25–7.55 m (4H, Harom), 9.40 s (1H, NH), 9.8 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008