Synthesis of derivatives of 5-(4,5-dihydro-1H-3-pyrazolyl)-3,4-dihydro- 2(1H)-pyrimidone

Full text of DOI:10.1007/s10593-009-0343-2

Chemistry of Heterocyclic Compounds, Vol. 45, No. 7, 2009
SYNTHESIS OF DERIVATIVES OF
5-(4,5-DIHYDRO-1H-3-PYRAZOLYL)-
3,4-DIHYDRO-2(1H)-PYRIMIDONE
M. A. Kolosov1* and V. D. Orlov1
Keywords: hydrazines, 4,5-dihydro-3H-pyrazoles, 5-cinnamoyl-3,4-dihydro-2(1H)-pyrimidones,
condensation.
In previous work [1], we showed that hydrazines react with 5-acetyl-1-ethyl-4-phenyl-3,4-dihydro-
2(1H)-pyrimidones at the acetyl group and C-6 in the heterocyclic ring to give derivatives of hexahydro-
[4,5-d]pyrimidin-6-one. The presence of a cinnamoyl group in compound 1a-f complicates the reaction of these
compounds with hydrazines since both cross-conjugated enone fragments can enter the reaction. A priori, such a
reaction could take place either at the 5-cinnamoyl group (a) or at the endocyclic enone group (b).
We have found that compound 1a-f in ethanol react with hydrazines in the presence of HCl upon
heating at reflux as heterocyclic chalcone analogs. The reaction of compound 1d with phenylhydrazine was also
carried out in ethanol in the presence of KOH but the yield of compound 2f in this case is only 25% in contrast
to 43% in acid medium.
Products 2a-h are solid colorless or yellow compounds possessing luminescence in the solid state as
well as in neutral and alkaline ethanolic solutions.
1
The H NMR spectra were taken on a Varian Mercury VX-200 spectrometer at 200 MHz in DMSO-d6
with TMS as the internal standard. The IR spectra were taken on a Specord IR-75 spectrometer for KBr pellets.
The mass spectra were taken on an Agillent 1100 LC-MS.
Ketones 1a-f were obtained according to our previous work [2].
Pyrimidones 2a-h (General Method). A solution of corresponding ketone 1 (0.8 mmol), hydrazine
(8 mmol), and five drops of concentrated hydrochloric acid in 4 ml ethanol was heated at reflux for 3 h. The
product was filtered off and washed thrice with 5 ml portions of 10:20:1 ethanol–water–piperidine.
1-Ethyl-5-[5-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-4-phenyl-3,4-dihydro-
2(1H)-pyrimidone (2a) was obtained in 22% yield; mp 188-190°C (EtOH). IR spectrum, ν, cm-1: 1502, 1608,
1682, 2923, 3063. 1H NMR spectrum, δ, ppm (J, Hz): 7.58 (1H, br. d, J = 2.8, NH); 6.72 (1H, s, H-6); 6.40-7.40
(14H, m, ArH); 5.43 (1H, d, J = 2.8, H-4); 5.07-5.32 (1H, m, CH); 3.68 (3H, s, OCH3); 3.0-3.4 (3H, m,
CH3CH2 + CH); 2.60-2.90 (1H, m, CH); 1.09 (3H, t, J = 7.0, CH3). Found, %: N 12.57. C28H28N4O2. Calculated,
%: N 12.38.
_______
* To whom correspondence should be addressed, e-mail: kolosov@univer.kharkov.ua.
1 V. N. Karazin Kharkiv National University, Kharkiv 61077, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1093-1096, July, 2009. Original
article submitted October 30, 2008.
0009-3122/09/4507-0873©2009 Springer Science+Business Media, Inc.
873

Ph
O
R
HN
O
N
R1
R2
1a–f
+
R3NHNH2
EtOH / H
b)
a)
N
R3
Ph
Ph
N
HN
N
R2
HN
N
N
O
R3
R2
R
O
N
R1
R1
R
2a–h
1 a R = H, b–f R = Me; a, c–f R1 = Et, b R1 = Me; a, b, d R2 = OMe, c R2 = H, e R2= NMe2,
f R = Br; 2 a R = H, b–h R = Me; a, c–h R1 = Et, b R1 = Me, a, b, d–f R2 = OMe, c R2 = H,
g R2 = NMe2, h R2 = Br; a–c, f–h R3 = Ph, d R3 = H, e R3 = Et
5-[5-(4-Methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-1,6-dimethyl-4-phenyl-3,4-dihydro-
2(1H)-pyrimidone (2b) was obtained in 32% yield; mp 243-245°C (EtOH). IR spectrum, ν, cm-1: 1502, 1596,
1
1675, 2916, 3076. H NMR spectrum, δ, ppm (J, Hz): 7.69 (1H, br. d, J = 3.2, NH); 7.15-7.40 (5H, m, ArH);
7.05 (2H, t, J = 7.6, ArH); 6.36-7.00 (7H, m, ArH); 5.37 (1H, d, J = 3.2, H-4); 5.21 (1H, dd, J1 = 11.2, J2 = 4.4,
CH); 3.72 (1H, dd, J1 = 16.8, J2 = 11.2, CH); 3.64 (3H, s, OCH3); 3.05 (3H, s, NCH3); 2.75 (1H, dd, J1 = 16.8,
J2 = 4.4, CH); 2.22 (3H, s, 6-CH3). Found, %: N 12.53. C28H28N4O2. Calculated, %: N 12.38.
1-Ethyl-5-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)-6-methyl-4-phenyl-3,4-dihydro-2(1H)-pyrimi-
done (2c) was obtained in 37% yield; mp 204-206°C (EtOH). IR spectrum, ν, cm-1: 1595, 1662, 3056, 3210,
1
3403. H NMR spectrum, δ, ppm (J, Hz): 7.60 (1H, br. d, J = 2.8, NH); 6.86-7.40 (12H, m, ArH); 6.79 (2H, t,
J = 7.8, ArH); 6.60 (1H, t, J = 7.4, ArH); 5.36 (1H, d, J = 2.8, H-4); 5.17-5.32 (1H, m, CH); 3.30-3.90 (3H, m,
CH3CH2 + CH); 2.80 (1H, dd, J1 = 16.6, J2 = 4.8, CH); 2.24 (3H, s, 6-CH3); 1.04 (3H, t, J = 7.0, CH3CH2).
Found, %: N 13.02. C28H28N4O. Calculated, %: N 12.83.
1-Ethyl-5-[5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-6-methyl-4-phenyl-3,4-dihydro-
2(1H)-pyrimidone (2d) was obtained in 29% yield; mp 157-159°C (EtOH). IR spectrum, ν, cm-1: 1682, 2923,
3230, 3290. 1H NMR spectrum, δ, ppm (J, Hz): 7.47 (1H, br. d, J = 2.8, N(3)H); 6.70-7.50 (6H, m, C6H5 + NH);
7.05 (2H, d, J = 8.6, ArH); 6.74 (2H, d, J = 8.6, ArH); 5.15 (1H, d, J = 2.8, H-4); 4.55 (1H, t, J = 9.4, CH); 3.68
(3H, s, OCH3); 3.60-3.90 (1H, m, CH); 3.00-3.60 (2H, m, CH2); 2.55 (1H, dd, J1 = 15.0, J2 = 9.4, CH); 2.16
(3H, s, 6-CH3); 0.99 (3H, t, J = 7.0, CH3CH2). Found, %: N 14.57. C23H26N4O2. Calculated, %: N 14.35.
1-Ethyl-5-[5-(1-ethyl-4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-6-methyl-4-phenyl-3,4-dihydro-
2(1H)-pyrimidone (2e) was obtained in 21% yield; mp 183-185°C (EtOH). IR spectrum, ν, cm-1: 1662, 2956,
3210. 1H NMR spectrum, δ, ppm (J, Hz): 7.54 (1H. br. d, J = 3.2, N(3)H); 7.10-7.40 (7H, m, ArH); 6.85 (2H, d,
J = 8.6, ArH); 5.14 (1H, d, J = 4.0, H-4); 3.71 (3H, s, OCH3); 3.60-4.20 (2H, m, CH2); 3.00-3.60 (3H, m,
H Alk); 2.40-2.90 (2H, m, H Alk); 2.17 (3H, s, 6-CH3); 1.00 (3H, t, J = 7.0, CH3CH2); 0.97 (3H, t, J = 7.0,
CH3CH2). Found, %: N 13.20. C25H30N4O2. Calculated, %: N 13.39.
1-Ethyl-5-[5-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-6-methyl-4-phenyl-3,4-di-
hydro-2(1H)-pyrimidone (2f) was obtained in 43% yield; mp 194-195°C (EtOH); IR spectrum, ν, cm-1: 1596,
874

1
1669, 3050, 3183. H NMR spectrum, δ, ppm (J, Hz): 7.57 (1H, br. d, J = 2.6, NH); 6.40-7.40 (14H, m, ArH);
5.36 (1H, d, J = 2.6, H-4); 5.21 (1H, dd, J1 = 11.8, J2 = 5.0, CH); 3.66 (3H, s, OCH3); 3.40-4.00 (3H, m,
CH3CH2 + CH); 2.79 (1H, dd, J1 = 17.0, J2 = 5.0, CH); 2.25 (3H, s, 6-CH3); 1.05 (3H, t, J = 7.0, CH3CH2). Mass
spectrum, m/z (Irel, %): 467 [M+1]+ (100). Found, %: N 11.95. C29H30N4O2. Calculated, %: N 12.01.
5-[5-(4-Dimethylaminophenyl)-6-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-1-ethyl-4-phenyl-
3,4-dihydro-2(1H)-pyrimidone (2g) was obtained in 13% yield; mp 225-227°C (EtOH). IR spectrum, ν, cm-1:
1495, 1596, 1675, 2910, 3430. 1H NMR spectrum, δ, ppm (J, Hz): 7.59 (1H, br. d, J = 2.8, NH); 7.15-7.40 (5H,
m, ArH); 7.04 (2H, t, J = 8.0, ArH); 6.82 (2H, d, J = 8.0, ArH); 6.76 (2H, d, J = 8.0, ArH); 6.59 (1H, t, J = 8.0,
ArH); 6.47 (2H, d, J = 8.0, ArH); 5.34 (1H, d, J = 2.8, H-4); 5.12 (1H, dd, J1 = 11.2, J2 = 4.8, CH); 3.40-4.00
(3H, m, CH3CH2 + CH); 2.67-2.85 (1H, m, CH); 2.78 (6H, s, N(CH3)2); 2.23 (3H, s, 6-CH3); 1.03 (3H, t, J = 7.0,
CH3CH2). Found, %: N 14.91. C30H33N5O. Calculated, %: N 14.60.
5-[5-(4-Bromophenyl)-6-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-1-ethyl-4-phenyl-3,4-di-
hydro-2(1H)-pyrimidone (2h) was obtained in 25% yield; mp 233-235°C (EtOH). IR spectrum, ν, cm-1: 1595,
1
1669, 2916, 3063, 3210. H NMR spectrum, δ, ppm (J, Hz): 7.60 (1H, br. d, J = 2.8, NH); 7.20-7.40 (7H, m,
ArH); 7.08 (2H, t, J = 8.0, ArH); 6.87 (2H, d, J = 8.0, ArH); 6.81 (2H, d, J = 8.0, ArH); 6.63 (1H, t, J = 7.4,
ArH); 5.35 (1H, d, J = 2.8, H-4); 5.29 (1H, dd, J1 = 11.6, J2 = 4.6, CH); 3.20-4.00 (3H, m, CH3CH2 + CH); 2.82
(1H, dd, J1 = 16.0, J2 = 4.8, CH); 2.25 (3H, s, 6-CH3); 1.05 (3H, t, J = 7.0, CH3CH2). Found, %: N 10.81.
C28H27BrN4O. Calculated, %: N 10.87.
This work was carried out with the financial support of the GFFI State Basic Research Fund of Ukraine
(Grant No. F25/155-2008).
REFERENCES
1.
2.
M. A. Kolosov and V. D. Orlov, Khim. Geterotsikl. Soedin., 1586 (2007). [Chem. Heterocycl. Comp.,
43, 1349 (2007)].
M. A. Kolosov, V. D. Orlov, V. V. Vashchenko, S. V. Shishkina, and O. V. Shishkin, Collect. Czech.
Chem. Commun., 72, 1219 (2007).
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