A convenient synthesis of novel 1,3,4-triaryl-3,4-dihydropyrimidin-2(1H)- ones by cyclization of aromatic isocyanates with β-arylamino-1- phenylpropan-1-ones

Article abstract of DOI:10.1002/jhet.5570450423

(Chemical Equation Presented) A simple one-step method for preparation of novel 1,3,4-triaryl-3,4-dihydropyrimidin-2(1H)-ones has been developed by reaction of aromatic isocyanates with β-arylamino-1-phenylpropan-1-ones in refluxing toluene in the presence of KHSO₄ and HCl.

Full text of DOI:10.1002/jhet.5570450423

Jul-Aug 2008
1095
A Convenient Synthesis of Novel 1,3,4-Triaryl-3,4-
dihydropyrimidin-2(1H)-ones by Cyclization of Aromatic
Isocyanates with ꢀ-Arylamino-1-phenylpropan-1-ones
Na Xue,1, 2 Xiuyang Lu2 and Yongzhou Hu*, 1
1 ZJU-ENS joint laboratory of medicinal chemistry, College of Pharmaceutical Sciences, Zhejiang University,
Hangzhou, 310058, Zhejiang, P. R. China.
2 Department of Chemical and Biochemical Engineering, College of Material Sciences and Chemical
Engineering, Zhejiang University
huyz@zjuem.zju.edu.cn
Received August 30, 2007
R2
NCO
N
O
R2
N
O
N
H
R1
R1
1
2
3a-3m
A simple one-step method for preparation of novel 1,3,4-triaryl-3,4-dihydropyrimidin-2(1H)-ones has
been developed by reaction of aromatic isocyanates with ꢀ-arylamino-1-phenylpropan-1-ones in refluxing
toluene in the presence of KHSO4 and HCl.
J. Heterocyclic Chem., 45, 1095 (2008).
INTRODUCTION
simultaneously occupying 1,3,4-position of the pyrimidin-
2-one nucleus has seldom been reported. Thus, it is
significative to develop a method to obtain novel triaryl-
3,4-dihydropyrimidin-2(1H)-one derivatives due to the
potential biological profile of such compounds. In
continuation of Mamaev’s work, we developed a simple
and one-step method to prepare a series of new triaryl-
3,4-dihydropyrimidin-2(1H)-one derivatives using easily
available aromatic isocyanates and ꢀ-arylamino-1-
phenylpropan-1-ones.
Dihydropyrimidin-2(1H)-ones (DHPMs) and their
derivatives represent heterocyclic system that have drawn
significant attention due to their diverse therapeutic and
pharmacological properties [1]. They are medicinally
important as antiviral agents, antitumor agents,
antibacterial agents and anti-inflammatory agents [1a,2].
In the last two decades, appropriately functionalized
DHPM analogues have emerged as orally active
antihypertensive agents [3] and alpha-la adrenoceptor-
selective antagonists [4]. In addition, several marine
alkaloids containing the dihydropyrimidinone-5-carboxyl-
ate motifs also show interesting biological activities [5]. A
conventional synthesis of DHPMs first performed by P.
RESULTS AND DISCUSSION
The starting materials, substituted phenyl isocyanates
1, are commercially available and substituted ꢀ-phenyl-
amino-1-phenylpropan-1-ones 2 were easily prepared
according to the reported procedure [12,13]. A mixture of
1.1 equimolar 4-chlorophenyl isocyanate 1a and ꢀ-4-
chlorophenylamino-1-phenylpropan-1-one 2a was
refluxed in toluene in the presence of KHSO4 and HCl for
3 h. To our delight, the reaction proceeded smoothly and
afforded the target compound 1,3-bis(4-chlorophenyl)-4-
phenyl-3,4-dihydropyrimidin-2(1H)-one 3a in 54% yield
(Scheme 1) (Table 1, entry 1).
With the reaction condition described above, various
hitherto unknown triaryl-3,4-dihydropyrimidin-2(1H)-
ones were obtained in moderate yields, as shown in Table
1 (entries 1-13). Aromatic isocyanate with both electron-
withdrawing and electron-releasing substituents readily
provided triaryl-3,4-dihydropyrimidin-2(1H)-ones. The
assigned molecular structures of new compounds 3a-m
Biginelli in 1893 involves
a
three-component
condensation of 1,3-dicarbonyl compounds, aldehydes
and urea under strongly acidic conditions with relatively
low yields [6]. In order to improve the efficiency of the
Biginelli reaction, more efficient conditions have been
found using Lewis acids as catalysts [7]. Additionally, the
use of ionic liquids [8], microwave irradiation [9] and
ultrasonic [10] mediated methods have also been
developed for synthesis of 3,4-dihydropyrimidin-2(1H)-
one derivatives. Besides, Mamaev et al. reported a two-
steps synthesis method to prepare 3,4-dihydropyrimidin-
2(1H)-one derivatives using 3-phenylamino-1-propanones
and substituted isocynanates and giving the intermediates
ꢀ-(N-phenylureido)ketones, but the total yields were very
poor [11]. In addition, to our knowledge, the synthesis of
the 3,4-dihydropyrimidin-2(1H)-ones with triaryl group

1096
N. Xue, X. Lu and Y. Hu
Vol 45
Scheme 1
R2
NCO
N
O
R2
toluene
N
N
O
H
HCl / KHSO4
R1
1
2
R1
3
Table 1.
Synthesis of 3,4-dihydropyrimdin-2(1H)-ones 3 by cyclization reaction of aromatic isocyanates 1 with ꢀ-arylamino-1-phenylpropan-1-ones 2
Entry
Product
R1
R2
Yield (%) [a]
1
2
3
3a
3b
3c
3d
3e
3f
4-Cl
4-CH3
4-OCH3
4-Cl
4-Cl
4-Cl
4-Cl
H
54
48
35
32
43
30
45
37
39
46
40
34
38
4
3,4,5-(OCH3)3
4-Cl
3,4,5-(OCH3)3
5
6
H
7
3g
3h
3i
H
H
H
8
9
4-OCH3
4-CH3
3-Cl
3-Cl
3-Br
3-CH3
4-OCH3
4-Cl
H
10
11
12
13
3j
3k
3l
H
3m
H
[a] Isolated yields of purified products.
Scheme 2
O
R2
N
N
O
R2
O
R1
N
H
N
C
O
H
2
1
R1
4
R2
R2
N
N
HO
-H2O
N
O
N
O
R1
R1
5
3
1
are based on rigorous spectroscopic analysis including H
NMR, MS and elemental analysis.
pyrimidin-2(1H)-one 5. Then, dehydration of 5 under
acidic conditions gives the target compound 3.
Furthermore, the most plausible mechanism for the
formation of 3,4-dihydropyrimidin-2(1H)-ones is presented
in Scheme 2. First, nucleophilic addition reaction of ꢀ-
arylamino-1-phenylpropan-1-one 1 to aromatic isocyanate
2 generate the intermediate 4, which is rapidly cyclized by
intramolecular nucleophilic addition to give tetrahydro-
In summary, a simple and one-step method for
preparation novel 1,3,4-triaryl-3,4-dihydropyrimidin-
2(1H)-ones had been developed by reaction of aromatic
isocyanates with ꢀ-arylamino-1-phenylpropan-1-ones in
the presence of KHSO4 and HCl in refluxing toluene. The
starting materials were easily obtained and the operation

Jul-Aug 2008
A Convenient Synthesis of Novel 1,3,4-Triaryl-3,4-dihydropyrimidin-2(1H)-ones
1097
3.26-3.29 (t, 2H, J = 6.4 Hz, CH2), 3.58-3.61 (t, 2H, J = 6.4 Hz,
CH2), 4.30 (br, 1H, NH), 6.49-6.51 (d, 1H, J = 8.0 Hz, Ar-H),
6.62 (s, 1H, Ar-H), 6.65-6.67 (d, 1H, J = 8.0 Hz, Ar-H), 7.05-
7.08 (t, 1H, J = 8.0 Hz, Ar-H), 7.45-7.49 (t, 2H, J = 8.0 Hz, Ar-
H), 7.56-7.60 (t, 1H, J = 8.0 Hz, Ar-H), 7.94-7.96 (d, 2H, J = 8.0
Hz, Ar-H).
was convenient. Further work is in progress to screen the
biological activities of the series of 1,3,4-triaryl-3,4-
dihydropyrimidin-2(1H)-one derivatives.
EXPERIMENTAL
3-[(3-Bromophenyl)amino]-1-phenyl-1-propanone (2f). 57%
Yield, mp 116-118 °C; 1H NMR (400 MHz, CDCl3) ꢁ: 3.26-3.28
(t, 2H, J = 6.4 Hz, CH2), 3.57-3.60 (t, 2H, J = 6.4 Hz, CH2), 4.25
(br, 1H, NH), 6.53-6.55 (d, 1H, J = 8.0 Hz, Ar-H), 6.77 (s, 1H, Ar-
H), 6.80-6.82 (d, 1H, J = 8.0 Hz, Ar-H), 7.00-7.03 (t, 1H, J = 8.0
Hz, Ar-H), 7.45-7.49 (t, 2H, J = 8.0 Hz, Ar-H), 7.56-7.60 (t, 1H, J
= 8.0 Hz, Ar-H), 7.94-7.96 (d, 2H, J = 8.0 Hz, Ar-H).
3-[(3-Methylphenyl)amino]-1-phenyl-1-propanone (2g).
51% Yield, mp 88-90 °C; 1H NMR (400 MHz, CDCl3) ꢁ: 2.29
(s, 3H, CH3), 3.27-3.30 (t, 2H, J = 6.4 Hz, CH2), 3.61-3.64 (t,
2H, J = 6.4 Hz, CH2), 4.07 (br, 1H, NH), 6.47-6.49 (m, 2H, Ar-
H), 6.54-6.56 (d, 1H, J = 8.0 Hz, Ar-H), 7.06-7.11 (t, 1H, J = 8.0
Hz, Ar-H), 7.45-7.49 (t, 2H, J = 8.0 Hz, Ar-H), 7.56-7.58 (t, 1H,
J = 8.0 Hz, Ar-H), 7.95-7.97 (d, 2H, J = 8.0 Hz, Ar-H).
General Procedure for the Synthesis of 1,3,4-Triaryl-3,4-
dihydropyrimidin-2(1H)-ones (compound 3a as example). To
a solution of 4-chlorophenyl isocyanate 1a (1.1 mmol) and ꢀ-4-
chlorophenylamino-1-phenylpropan-1-one 2a (1 mmol) in 5 mL
toluene, added KHSO4 (0.01 mmol) and HCl saturated toluene
(0.2 mL). The reaction mixture was stirred and refluxed for 3
hrs. After cooling to room temperature, the reaction mixture was
quenched with H2O (10 mL), and extracted with ethyl acetate
(3ꢁ20 mL). The organic layer was dried over anhydrous Na2SO4.
After evaporation of the solvent, the crude product was purified
by chromatography on silica gel using petroleum ether-ethyl
acetate (4:1) as eluent, to offer pure product 3a.
Melting points were measured on a B-540 Bꢀchi melting
point apparatus and are uncorrected. 1H NMR spectra were
recorded on a Brucker Advance DMX 400-MHz spectrometer
with TMS as the internal standard. Chemical shifts are expressed
in parts per million (ppm). Mass Spectra (MS) analyse, ESI
(positive) were performed with an Esquire-LC-00075
spectrometer. Elemental analysis was carried out on an ERBA-
1110 analyzer.
General Procedure for the Synthesis of ꢀ-Arylamino-1-
phenylpropan-1-ones 2. Procedure (i): A suspension of
acetophenone (0.1 mol), dimethyl amine hydrochloride (0.13
mol) and paraformaldehyde (0.13 mol) in a mixture of 18 mL of
ethanol and 0.3 mL of conc. HCl was refluxed for 2 hrs. After
cooling, 100 mL of acetone was added. The white crystals
formed were collected, washed with acetone and dried in vacuo
to yield 16.9 g (79%) of ꢀ-dimethylaminopropiophenone
hydrochloride, mp 152-154 °C (lit. [12], mp 153 °C).
Procedure (ii): Equimolar quantities of ꢀ-dimethylamino-
propiophenone hydrochloride and arylamines (aniline; p-
anisidine; m,p-toluidine; m,p-chloroaniline; and m-bromo-
aniline) were refluxed for 2 hrs on a boiling water-bath using
50% ethyl alcohol as solvent. The solid which separated out on
cooling was filtered and thoroughly washed with water and cold
ethyl alcohol. The resulting ꢀ-arylamino-1-phenylpropan-1-ones
2 were crystallised from EtOH.
3-[(4-Chlorophenyl)amino]-1-phenyl-1-propanone (2a).
92% Yield, mp 134-135 °C (lit. [14], mp 133-134.5 °C); H
1,3-Bis(4-chlorophenyl)-6-phenyl-3,4-dihydropyrimidin-
2(1H)-one (3a). Mp 112-114 °C; 1H NMR (400 MHz, CDCl3) ꢁ:
4.43-4.44 (d, 2H, J = 4.4 Hz, CH2), 5.38-5.40 (t, 1H, J = 4.4 Hz,
=CH-), 7.10-7.13 (m, 2H, Ar-H), 7.34-7.35 (m, 4H, Ar-H), 7.16-
7.18 (m, 7H, Ar-H). ESIMS m/z = 395 (MH+); Anal. Calcd. for
C22H16Cl2N2O: C, 66.85; H, 4.08; N, 7.09. Found: C, 66.89; H,
4.13; N, 7.05.
1
NMR (400 MHz, CDCl3) ꢁ: 3.25-3.28 (t, 2H, J = 6.4 Hz, CH2),
3.56-3.60 (t, 2H, J = 6.4 Hz, CH2), 4.16 (br, 1H, NH), 6.55-6.57
(d, 2H, J = 8.8 Hz, Ar-H), 7.11-7.13 (d, 2H, J = 8.8 Hz, Ar-H),
7.45-7.49 (t, 2H, J = 7.6 Hz, Ar-H), 7.56-7.60 (t, 1H, J = 7.6 Hz,
Ar-H), 7.94-7.96 (d, 2H, J = 7.6 Hz, Ar-H).
3-(Phenylamino)-1-phenyl-1-propanone (2b). 71% Yield,
1
mp 109-111 °C (lit. [14], mp 109-111 °C); H NMR (400 MHz,
1-(4-Methylphenyl)-3-(4-chlorophenyl)-6-phenyl-3,4-dihy-
dropyrimidin-2(1H)-one (3b). Mp 135-137 °C; H NMR (400
1
CDCl3) ꢁ: 3.28-3.31 (t, 2H, J = 6.4 Hz, CH2), 3.61-3.64 (t, 2H, J
= 6.4 Hz, CH2), 4.12 (br, 1H, NH), 6.64-6.66 (d, 2H, J = 8.0 Hz,
Ar-H), 6.69-6.73 (d, 1H, J = 8.0 Hz, Ar-H), 7.16-7.20 (t, 2H, J =
8.0 Hz, Ar-H), 7.45-7.48 (t, 2H, J = 8.0 Hz, Ar-H), 7.56-7.59 (t,
1H, J = 8.0 Hz, Ar-H), 7.94-7.96 (d, 2H, J = 8.0 Hz, Ar-H).
3-[(4-Methoxyphenyl)amino]-1-phenyl-1-propanone (2c).
67% Yield, mp 110-111 °C (lit. [14], mp 111 °C); 1H NMR (400
MHz, CDCl3) ꢁ: 3.25-3.28 (t, 2H, J = 6.4 Hz, CH2), 3.55-3.58 (t,
2H, J = 6.4 Hz, CH2), 3.75 (s, 3H, OCH3), 6.62-6.64 (d, 2H, J =
8.0 Hz, Ar-H), 6.78-6.80 (d, 2H, J = 8.0 Hz, Ar-H), 7.44-7.48 (t,
2H, J = 8.0 Hz, Ar-H), 7.55-7.59 (t, 1H, J = 8.0 Hz, Ar-H), 7.94-
7.96 (d, 2H, J = 8.0 Hz, Ar-H).
3-[(4-Methylphenyl)amino]-1-phenyl-1-propanone (2d).
78% Yield, mp 109-111 °C (lit. [14], mp 109-111 °C); 1H NMR
(400 MHz, CDCl3) ꢁ: 2.24 (s, 3H, CH3), 3.26-3.29 (t, 2H, J = 6.4
Hz, CH2), 3.58-3.62 (t, 2H, J = 6.4 Hz, CH2), 4.12 (br, 1H, NH),
6.58-6.60 (d, 2H, J = 8.0 Hz, Ar-H), 6.99-7.01 (d, 2H, J = 8.0
Hz, Ar-H), 7.44-7.48 (t, 2H, J = 7.6 Hz, Ar-H), 7.55-7.59 (t, 1H,
J = 7.6 Hz, Ar-H), 7.94-7.96 (d, 2H, J = 7.6 Hz, Ar-H).
MHz, CDCl3) ꢁ: 1.67 (s, 3H, CH3), 4.42-4.44 (d, 2H, J = 4.4 Hz,
CH2), 5.32-5.34 (t, 1H, J = 4.4 Hz, =CH-), 6.93-6.95 (d, 2H, J =
8.0 Hz, Ar-H), 7.08-7.10 (d, 2H, J = 8.0 Hz, Ar-H), 7.14-7.18
(m, 5H, Ar-H), 7.33-7.35 (m, 4H, Ar-H). ESIMS m/z = 375
(MH+); Anal. Calcd. for C23H19ClN2O: C, 73.69; H, 5.11; N,
7.47. Found: C, 73.63; H, 5.16; N, 7.42.
1-(4-Methoxyphenyl)-3-(4-chlorophenyl)-6-phenyl-3,4-di-
hydropyrimidin-2(1H)-one (3c). Oil; 1H NMR (400 MHz,
CDCl3) ꢁ: 3.68 (s, 3H, OCH3), 4.43-4.44 (d, 2H, J = 4.4 Hz,
CH2), 5.29-5.31 (t, 1H, J = 4.4 Hz, =CH-), 6.66-6.68 (d, 2H, J =
8.4 Hz, Ar-H), 7.11-7.18 (m, 7H, Ar-H), 7.34-7.38 (m, 4H, Ar-
H). ESIMS m/z = 391 (MH+); Anal. Calcd. for C23H19ClN2O2: C,
70.68; H, 4.90; N, 7.17. Found: C, 70.63; H, 4.95; N, 7.12.
1-(3,4,5-Trimethoxyphenyl)-3-(4-chlorophenyl)-6-phenyl-
3,4-dihydropyrimidin-2(1H)-one (3d). Oil; 1H NMR (400
MHz, CDCl3) ꢁ: 3.68 (s, 6H, OCH3ꢁ2), 3.72 (s, 3H, OCH3),
4.43-4.45 (d, 2H, J = 4.4 Hz, CH2), 5.35-5.37 (t, 1H, J = 4.4 Hz,
=CH-), 6.47 (s, 2H, Ar-H), 7.16-7.19 (m, 5H, Ar-H), 7.35-7.38
(m, 4H, Ar-H). ESIMS m/z = 451 (MH+); Anal. Calcd. for
C25H23ClN2O4: C, 66.59; H, 5.14; N, 6.21. Found: C, 66.63; H,
5.10; N, 6.18.
3-[(3-Chlorophenyl)amino]-1-phenyl-1-propanone (2e).
1
55% Yield, mp 111-113 °C; H NMR (400 MHz, CDCl3) ꢁ:

1098
N. Xue, X. Lu and Y. Hu
Vol 45
1-(4-Chlorophenyl)-3-phenyl-6-phenyl-3,4-dihydropyrim-
1-Phenyl-3-(3-bromophenyl)-6-phenyl-3,4-dihydropyrim-
idin-2(1H)-one (3l). Mp 132-134 °C; 1H NMR (400 MHz,
CDCl3) ꢀ: 4.39-4.40 (d, 2H, J = 4.4 Hz, CH2), 5.42-5.43 (t, 1H, J
= 4.4 Hz, =CH-), 7.29-7.33 (m, 3H, Ar-H), 7.37-7.46 (m, 7H,
Ar-H), 7.58-7.59 (m, 2H, Ar-H), 7.67-7.69 (m, 2H, Ar-H).
ESIMS m/z = 405 (MH+); Anal. Calcd. for C22H17BrN2O: C,
65.20; H, 4.23; N, 6.91. Found: C, 65.16; H, 4.25; N, 6.88.
1-Phenyl-3-(3-methylphenyl)-6-phenyl-3,4-dihydropyrim-
idin-2(1H)-one (3e). Mp 107-109 °C; 1H NMR (400 MHz,
CDCl3) ꢀ: 4.48-4.49 (d, 2H, J = 4.4 Hz, CH2), 5.41-5.43 (t, 1H, J
= 4.4 Hz, =CH-), 7.11-7.15 (m, 2H, Ar-H), 7.20-7.23 (m, 7H,
Ar-H), 7.25-7.28 (m, 1H, Ar-H), 7.41-7.42 (m, 4H, Ar-H).
ESIMS m/z = 361 (MH+); Anal. Calcd. for C22H17ClN2O: C,
72.23; H, 4.75; N, 7.76. Found: C, 72.26; H, 4.79; N, 7.73.
1-(3,4,5-Trimethoxyphenyl)-3-phenyl-6-phenyl-3,4-dihy-
1
1
dropyrimidin-2(1H)-one (3f). Mp 119-121 °C; H NMR (400
idin-2(1H)-one (3m). Mp 110-112 °C; H NMR (400 MHz,
MHz, CDCl3) ꢀ: 3.69 (s, 6H, OCH3ꢀ2), 3.73 (s, 3H, OCH3),
4.48-4.49 (d, 2H, J = 4.4 Hz, CH2), 5.38-5.40 (t, 1H, J = 4.4 Hz,
=CH-), 6.52 (s, 2H, Ar-H), 7.15-7.23 (m, 6H, Ar-H), 7.42-7.43
(m, 4H, Ar-H). ESIMS m/z = 417 (MH+); Anal. Calcd. for
C25H24N2O4: C, 72.10; H, 5.81; N, 6.73. Found: C, 72.07; H,
5.86; N, 6.69.
CDCl3) ꢀ: 2.39 (s, 3H, CH3), 4.38-4.39 (d, 2H, J = 4.4 Hz, CH2),
5.40-5.42 (t, 1H, J = 4.4 Hz, =CH-), 7.09-7.15 (m, 2H, Ar-H),
7.19-7.23 (m, 3H, Ar-H), 7.31-7.35 (m, 3H, Ar-H), 7.39-7.41
(m, 4H, Ar-H), 7.67-7.70 (m, 2H, Ar-H). ESIMS m/z = 341
(MH+); Anal. Calcd. for C23H20N2O: C, 81.15; H, 5.92; N, 8.23.
Found: C, 81.10; H, 5.86; N, 8.33.
1,3,6-Triphenyl-3,4-dihydropyrimidin-2(1H)-one (3g). Oil;
1H NMR (400 MHz, CDCl3) ꢀ: 4.46-4.47 (d, 2H, J = 4.4 Hz,
CH2), 5.35-5.37 (t, 1H, J = 4.4 Hz, =CH-), 6.69-6.74 (m, 2H,
Ar-H), 6.91-6.95 (m, 2H, Ar-H), 7.01-7.05 (m, 1H, Ar-H), 7.21-
7.24 (m, 2H, Ar-H), 7.26-7.29 (m, 4H, Ar-H), 7.43-7.45 (m, 4H,
Ar-H). ESIMS m/z = 327 (MH+); Anal. Calcd. for C22H18N2O: C,
80.96; H, 5.56; N, 8.58. Found: C, 80.94; H, 5.57; N, 8.59.
1-Phenyl-3-(4-methoxyphenyl)-6-phenyl-3,4-dihydropyr-
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1
imidin-2(1H)-one (3h). Mp 132-134 °C; H NMR (400 MHz,
CDCl3) ꢀ: 3.40 (s, 3H, OCH3), 4.12-4.14 (d, 2H, J = 4.4 Hz,
CH2), 5.29-5.30 (t, 1H, J = 4.4 Hz, =CH-), 6.94-6.96 (d, 2H, J =
8.8 Hz, Ar-H), 7.22-7.24 (m, 1H, Ar-H), 7.29-7.33 (m, 5H, Ar-
H), 7.38-7.40 (m, 4H, Ar-H), 7.66-7.69 (m, 2H, Ar-H). ESIMS
m/z = 357 (MH+); Anal. Calcd. for C23H20N2O2: C, 77.51; H,
5.66; N, 7.86. Found: C, 77.55; H, 5.70; N, 7.89.
1-(4-Methoxyphenyl)-3-(4-methylphenyl)-6-phenyl-3,4-
1
dihydropyrimidin-2(1H)-one (3i). Oil; H NMR (400 MHz,
CDCl3) ꢀ: 2.35 (s, 3H, CH3), 3.68 (s, 3H, OCH3), 4.44-4.45 (d,
2H, J = 4.4 Hz, CH2), 5.29-5.31 (t, 1H, J = 4.4 Hz, =CH-), 6.65-
6.67 (d, 2H, J = 8.4Hz, Ar-H), 7.13-7.20 (m, 9H, Ar-H), 7.26-
7.30 (d, 2H, J = 8.4Hz, Ar-H). ESIMS m/z = 371 (MH+); Anal.
Calcd. for C24H22N2O2: C, 77.81; H, 5.99; N, 7.56. Found: C,
77.85; H, 6.01; N, 7.53.
[6a] Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360. (b) Folkers, K.;
Johnson, T. B. J. Am. Chem. Soc. 1933, 55, 3781.
[7a] Kappe, C. O.; Falsone, S. F. Synlett 1998, 718. (b) Hu, E. H.;
Sidler, D. R.; Dolling, U. H. J. Org. Chem. 1998, 63, 3454. (c) Lu, J.;
Ma, H. Synlett 2000, 63. (d) Ma, Y.; Qian, C.; Wang, L.; Yang, M. J.
Org. Chem. 2000, 65, 3864. (e) Ranu, B. C.; Hayra, A.; Jana, U. J. Org.
Chem. 2000, 65, 6270.
[8] Peng, J.; Deng, Y. Tetrahedron Lett. 2001, 42, 5917.
[9] Kappe, C. O.; Kumar, D.; Varma, R. S. Synthesis 1999, 1799.
[10] Zhang, X.; Li, Y.; Liu, C.; Wang, J. J. Mol. Catal. A: Chem.
2006, 253, 207.
[11] Mamaev, V. P.; Nilko’skaya, G. S.; Lyubimova, E. N. Izv.
Sibir. Otd. Akad. Nauk SSSR, Ser. Khim. Nauk (Russian) 1971, 2, 86;
Chem. Abstr. 1972, 76, 14479g.
[12] Abid, M.; Azam, A. Eur. J. Med. Chem. 2005, 9, 935.
[13] Modak, A. S.; Gogte, V. N.; Tilak, B. D. Indian J. Chem.
Sect. B 1984, 10, 907.
1-(4-Chlorophenyl)-3-(3-chlorophenyl)-6-phenyl-3,4-dihydro-
1
pyrimidin-2(1H)-one (3j). Oil; H NMR (400 MHz, CDCl3) ꢀ:
4.47-4.48 (d, 2H, J = 4.4 Hz, CH2), 5.42-5.44 (t, 1H, J = 4.4 Hz,
=CH-), 7.14-7.16 (m, 2H, Ar-H), 7.20-7.24 (m, 6H, Ar-H), 7.29-
7.33 (m, 2H, Ar-H), 7.35-7.38 (m, 2H, Ar-H), 7.45 (s, 1H, Ar-
H). ESIMS m/z = 395 (MH+); Anal. Calcd. for C22H16Cl2N2O: C,
66.85; H, 4.08; N, 7.09. Found: C, 66.81; H, 4.12; N, 7.11.
1-Phenyl-3-(3-chlorophenyl)-6-phenyl-3,4-dihydropyrim-
idin-2(1H)-one (3k). Mp 135-137 °C; 1H NMR (400 MHz,
CDCl3) ꢀ: 4.37-4.38 (d, 2H, J = 4.4 Hz, CH2), 5.42-5.44 (t, 1H, J
= 4.4 Hz, =CH-), 7.14-7.16 (m, 2H, Ar-H), 7.20-7.21 (m, 7H,
Ar-H), 7.29-7.33 (m, 2H, Ar-H), 7.35-7.38 (m, 2H, Ar-H), 7.45
(s, 1H, Ar-H). ESIMS m/z = 361 (MH+); Anal. Calcd. for
C22H17ClN2O: C, 73.23; H, 4.75; N, 7.76. Found: C, 73.19; H,
4.77; N, 7.72.
[14] Xu, X. J.; Chen, G. X. Acta. Chemica. Sinica. (Chinese)
1982, 4, 362; Chem. Abstr. 1982, 96, 162498g.