Expedient one-pot three-component catalyst-free access to 5,6-dihydropyrimidin-4(3H)-one derivatives

Article abstract of DOI:10.1007/s13738-014-0574-8

Abstract The synthesis of novel 5,6-dihydropyrimidin-4(3H)-one derivatives was accomplished in good yields via one-pot three-component condensation of Meldrum's acid, aldehydes and benzamidine in EtOH. Short reaction time, mild reaction condition, use of

Full text of DOI:10.1007/s13738-014-0574-8

J IRAN CHEM SOC
DOI 10.1007/s13738-014-0574-8
ORIGINAL PAPER
Expedient one‑pot three‑component catalyst‑free access
to 5,6‑dihydropyrimidin‑4(3H)‑one derivatives
Mehdi Ghandi · Maryam Jahangir Vazifeh
Received: 25 August 2014 / Accepted: 8 December 2014
© Iranian Chemical Society 2014
Abstract The synthesis of novel 5,6-dihydropyrimidin-
4(3H)-one derivatives was accomplished in good yields via
one-pot three-component condensation of Meldrum’s acid,
aldehydes and benzamidine in EtOH. Short reaction time,
mild reaction condition, use of simple experimental proce-
dure and prompt isolation of the products are some advan-
tages of this protocol.
anticonvulsant [28], antinociceptive [29, 30], anti-amoebic
[31] and anti-inflammatory [32] agents.
As an important subclass of pyrimidine, the dihydropy-
rimidine and their derivatives are known as calcium chan-
nel modulators [33], mitotic kinesine inhibitors [34], adr-
energic receptor antagonists [35], antibacterial [36], and
antiviral agents [37].
Pyrimidine or pyrimidinone derivatives have tradition-
ally been synthesized via condensation of a Michael accep-
tor with a uronium-containing molecule such as urea [38],
thiourea [39], amidines [40], guanidines [41] or their deriv-
atives. Due to the rather slow rates, 1 to 2 days are needed
for the reactions to be completed. Therefore, different cata-
lysts including BF3.OEt2 [42], LaCl3.H2O [43], InBr3 [44],
HY [45], amberlyst-15 or Nafion-H [46], montmorillonite-
KSF [47], MCM-41-R-SO3H [48], MCM-41 supported
FeCl3 [49] and amino-functionalized MCM-41 [50] have
been used for these reactions. In addition, microwave radia-
tion has also been used to accelerate reaction rates [40].
In continuation of our own interest in MCRs [51–54],
herein we report an expedient one-pot three-component
access to 5,6-dihydropyrimidin-4(3H)-one derivatives via
condensation of Meldrum’s acid, aldehydes and benzami-
dine in EtOH.
Keywords 5,6-Dihydropyrimidin-4(3H)-one ·
Benzamidine · Meldrum’s acid · Three-component reaction
Introduction
The so-called multicomponent reactions (MCRs) are one-
pot processes in which at least three or more different sim-
ple substrates react for the preparation of target materials
[1–7]. These reactions have gained much attention during
the past years and frequently occur not through a single-
step procedure, but rather by several sequential steps or
multicomponent cascade or domino reactions [8–13]. Sim-
plicity, greater efficiency and atom economy with genera-
tion of molecular complexity and diversity in one-pot trans-
formation are some of the advantages of these reactions.
The six-membered pyrimidines, abundantly widespread
among natural bases [14–16], are an important class of
heterocycles to medicinal chemistry due to their biologi-
cal activities. These compounds have been reported as
antitumor [17–20], interferon inducer [21–23], antivi-
ral [24], anti-hypertensive [25, 26], hypoglycemic [27],
Experimental
General information
All commercially available chemicals and reagents were
purchased from Merck Chemical Company and used
without further purification. Melting points were deter-
mined with an Electrothermal model 9100 apparatus and
are uncorrected. IR spectra were recorded on a Shimadzu
M. Ghandi (*) · M. J. Vazifeh
School of Chemistry, College of Science, University of Tehran,
P.O. Box 14155 6455, Tehran, Iran
e-mail: ghandi@khayam.ut.ac.ir
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J IRAN CHEM SOC
1
4300 spectrophotometer, in cm−1. 1H and 13C NMR spectra
were recorded on a Bruker DRX-500-AVANCE spectrom-
eter at 300 (1H) and 75 MHz (13C) using CDCl3 as solvent
and with the residual solvent signal as internal reference
(CDCl3 7.24 and 77.0 ppm). Mass spectra of the products
were obtained with an HP (Agilent technologies) 5937
Mass Selective Detector. Elemental analyses were carried
out by a CHN-Rapid Heraeus elemental analyzer (Welles-
ley, MA, USA).
(C = O), 1,635 (C = N); H-NMR (300 MHZ, CDCl3):
δH = 2.36 (dd, J = 16.5, 13.6 Hz, 1H, CHCO), 3.01 (dd,
J = 16.6, 5.0 Hz, 1H, CHCO), 5.28 (dd, J = 13.6, 5.0 Hz,
1H, CHN), 7.31 (dd, J = 8.4, 2.0 Hz, 1H, Ar), 7.42 (d,
J = 2.0 Hz, 1H, Ar), 7.47–7.58 (m, 3H, Ar), 7.63 (d,
J = 8.4 Hz, 1H, Ar), 7.87 (m, 2H, Ar), 8.80 (s, 1H, NH);
13C NMR (75 MHz, CDCl3): δC = 35.8, 55.7, 126.5, 127.7,
129.0, 129.2, 131.7, 131.9, 132.9, 133.7, 138.7, 152.1, 170.2
(CO); EI-MS: m/z (%): 322(20, M+, 2[37Cl], 320 (77, M+,
[37Cl], [35Cl]), 318 (84, M+, 2[35Cl]), 291 (12), 283 (56),
267 (12), 226 (9), 173 (22), 104(100), 91(17), 77 (63 %);
Anal. Calcd for C16H12Cl2N2O: C, 60.21; H, 3.79; N, 8.78.
Found: C, 59.93; H, 3.61; N, 8.81.
General procedure for the preparation of 2a–n
A mixture containing benzamidine hydrochloride (0.210 g,
1.2 mmol), triethylamine (0.101 g, 1.0 mmol), aldehydes
1a–n (1.0 mmol) and Meldrum’s acid (0.144 g, 1.0 mmol)
in EtOH (3 mL) was stirred at reflux for 1 h. After comple-
tion as indicated by TLC, the solid was filtered and washed
with EtOH to afford 2a–n.
2,6‑Diphenyl‑5,6‑dihydropyrimidin‑4(3H)‑one
(2d) White solid, mp: 185–187 °C, yield: 0.175 g (70 %).
IR (KBr) (νmax, cm−1): 3,239 (NH), 1,691 (C = O), 1,637
1
(C = N); H-NMR (300 MHZ, CDCl3): δH = 2.61 (dd,
J = 16.5, 12.4 Hz, 1H, CHCO), 2.88 (dd, J = 16.5, 5.4 Hz,
1H, CHCO), 4.98 (dd, J = 12.4, 5.3 Hz, 1H, CHN), 7.29-
7.34 (m, 1H, Ar), 7.39 (t, J = 7.4 Hz, 2H, Ar), 7.46-7.56
(m, 5H, Ar), 7.90 (d, J = 6.8 Hz, 2H, Ar), 9.13 (s, 1H, NH);
13C NMR (75 MHz, CDCl3): δC = 37.5, 58.3, 126.6, 126.7,
127.4, 128.7, 128.8, 131.4, 133.2, 142.1, 151.4, 171.2 (CO);
EI-MS: m/z (%): 250 (100, M+), 221(22), 193 (9), 173 (5),
147 (1.6), 104 (61), 77 (16); Anal. Calcd for C16H14N2O
(250.11): C 76.78, H 5.64, N 11.19 %. Found: C 76.36, H
5.23, N, 11.14 %.
6‑Butyl‑2‑phenyl‑5,6‑dihydropyrimidin‑4(3H)‑one
(2a) White solid, mp: 105–107 °C, yield: 0.168 g (73 %).
IR (KBr) (νmax, cm−1): 3,288 (NH), 1,692 (C = O), 1,642
1
(C = N); H-NMR (300 MHZ, CDCl3): δH = 0.95 (t,
J = 7.0 Hz, 3H, CH3CH2), 1.36–1.86 (m, 6H, CH2CH2CH2),
2.31(dd, J = 16.4, 11.2 Hz, 1H, CHCO), 2.60 (dd, J = 16.4,
5.2 Hz, 1H, CHCO), 3.70–3.80 (m, 1H, CHN), 7.42–7.52
(m, 3H, Ar), 7.79 (d, J = 6.3 Hz, 2H, Ar), 8.67 (s, 1H,
NH); 13C NMR (75 MHz, CDCl3): δC = 14.0, 22.6, 28.1,
35.0, 35.5, 54.7, 126.5, 128.8, 131.1, 133.4, 151.5, 171.7
(C = O); EI-MS: m/z (%): 230 (21, M+), 215 (1.5), 201
(4), 173 (100), 159 (9), 104 (59), 77 (28); Anal. Calcd for
C14H18N2O (230.14): C 73.01, H 7.88, N 12.16 %. Found:
C 72.59, H 8.20, N 11.77 %.
6‑(4‑Bromophenyl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2e) White solid, mp: 210–212 °C, yield:
0.171 g (52 %). IR (KBr) (νmax, cm−1): 3,250 (NH), 1,694
1
(C = O), 1,633 (C = N); H-NMR (300 MHZ, CDCl3):
δH = 2.56 (dd, J = 16.5, 12.8 Hz, 1H, CHCO), 2.86 (dd,
J = 16.5, 5.2 Hz, 1H, CHCO), 4.93 (dd, J = 12.8, 5.2 Hz,
1H, CHN), 7.35 (d, J = 8.4 Hz, 2H, Ar), 7.46–7.57 (m,
5H, Ar), 7.85(d, J = 7.2 Hz, 2H, Ar), 8.47 (s, 1H, NH);
13C NMR (75 MHz, CDCl3): δC = 37.4, 57.8, 121.3, 126.5,
128.3, 128.9, 131.6, 131.8, 133.0, 141.2, 151.5, 170.2 (CO);
EI-MS: m/z (%): 330 (70, M+ [81Br]), 328 (49, M+ [79Br]),
299 (12), 273 (4), 249 (29), 104 (100), 77 (51); Anal. Calcd
for C16H13BrN2O (328.02): C 58.38, H 3.98, N 8.51 %.
Found: C 58.46, H 3.93, N 8.59 %.
6‑Phenethyl‑2‑phenyl‑5,6‑dihydropyrimidin‑4(3H)‑one
(2b) White solid, mp: 144–146 °C, yield: 0.222 g (80 %).
IR (KBr) (νmax, cm−1): 3,253 (NH), 1,692 (C = O), 1,639
1
(C = N); H-NMR (300 MHZ, CDCl3): δH = 1.88–2.00
(m, 1H, CHCHN), 2.04–2.16 (m, 1H, CHCHN), 2.35(dd,
J = 16.4, 11.8 Hz, 1H, CHCO), 2.60 (dd, J = 16.5, 5.1 Hz,
1H, CHCO), 2.85–3.02 (m, 2H, CH2Ph), 3.71-3.81 (m,
1H, CHN), 7.19–7.34 (m, 5H, Ar), 7.44-7.55(m, 3H, Ar),
7.82 (d, J = 6.7 Hz, 2H, Ar), 8.55 (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): δC = 32.2, 35.2, 37.4, 53.8, 125.9, 126.5,
128.4, 128.6, 128.9, 131.3, 133.3, 141.7, 150.5, 171.3 (CO);
EI-MS: m/z (%): 278 (27, M+), 249 (4), 174 (100), 145
(26), 104 (43), 91 (17), 77 (21); Anal. Calcd for C18H18N2O
(278.14): C 77.67, H 6.52, N 10.06 %. Found: C 77.46, H
6.23, N 10.16 %.
6‑(4‑Chlorophenyl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2f) White solid, mp: 195–197 °C, yield:
0.25 g (88 %). IR (KBr) (νmax, cm−1): 3,230 (NH), 1,696
1
(C = O), 1,633 (C = N); H-NMR (300 MHZ, CDCl3):
δH = 2.56 (dd, J = 16.5, 12.8 Hz, 1H, CHCO), 2.86 (dd,
J = 16.5, 5.2 Hz, 1H, CHCO), 4.95 (dd, J = 12.7, 5.2 Hz,
1H, CHN), 7.35-7.43 (m, 4H, Ar), 7.46-7.56 (m, 3H, Ar),
7.85(d, J = 6.8 Hz, 2H, Ar), 8.47 (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): δC = 37.4, 57.8, 126.5, 128.0, 128.8,
6‑(2,4‑Dichlorophenyl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2c) White solid, mp: 218–220 °C, yield:
0.217 g (68 %). IR (KBr) (νmax, cm−1): 3,246 (NH), 1,694
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J IRAN CHEM SOC
128.9, 131.6, 133.0, 133.2, 140.7, 151.5, 170.2 (CO);
EI-MS: m/z (%): 286 (47, M+ [37Cl]), 284 (100, M+ [35Cl]),
255 (22), 227 (7), 138 (21), 104 (80), 77 (34); Anal. Calcd
for C16H13ClN2O (284.07): C 67.49, H 4.60, N 9.84 %.
Found: C 67.48, H 4.49, N 9.94 %.
6‑(3‑Hydroxy‑4‑methoxyphenyl)‑2‑phenyl‑5,6‑dihydropy‑
rimidin‑4(3H)‑one (2j) White solid, mp: 178–180 °C,
yield: 0.186 g (63 %). IR (KBr) (νmax, cm−1): 3,439 (OH),
3,259 (NH), 1,695 (C = O), 1,640 (C = N); 1H-NMR (300
MHZ, CDCl3): δH = 2.59 (dd, J = 16.5, 12.1 Hz, 1H,
CHCO), 2.84 (dd, J = 16.5, 5.4 Hz, 1H, CHCO), 3.89 (s,
3H, Me), 4.90 (dd, J = 12.0, 5.4 Hz, 1H, CHN), 5.72 (s,
1H, OH), 6.84 (d, J = 8.3 Hz, 1H, Ph), 6.91 (dd, J = 8.3,
1.8 Hz, 1H, Ph), 7.03 (d, J = 1.8 Hz, 1H, Ph), 7.44–7.55
(m, 3H, Ph), 7.86 (d, J = 6.8 Hz, 2H, Ph), 8.60 (s, 1H, NH);
13C NMR (75 MHz, CDCl3): δC = 37.5, 56.0, 57.8, 110.8,
113.0, 118.0, 126.6, 128.8, 131.4, 133.1, 135.4, 145.8,
145.9, 151.1, 170.8 (CO); EI-MS: m/z (%): 296 (100, M+),
267 (22), 240 (4) 177 (15), 150 (16), 104 (39), 77 (20);
Anal. Calcd for C17H16N2O3 (296.12): C 68.91, H 5.44, N
9.45 %. Found: C 69.19, H 5.04; N 9.10 %.
2‑Phenyl‑6‑(p‑tolyl)‑5,6‑dihydropyrimidin‑4(3H)‑one
(2g) White solid, mp: 179–18 °C, yield: 0.14 g (53 %).
IR (KBr) (νmax cm−1): 3,255 (NH), 1,692 (CO), 1,642
1
(C = N); H-NMR (300 MHZ, CDCl3): δH = 2.36 (s,
3H, Me), 2.61 (dd, J = 16.5, 12.2 Hz, 1H, CHCO), 2.86
(dd, J = 16.5, 5.4 Hz, 1H, CHCO), 4.96 (dd, J = 12.1,
5.4 Hz, 1H, CHN), 7.19 (d, J = 7.9 Hz, 2H, Ar), 7.34
(d, J = 7.9 Hz, 2H, Ar), 7.45-7.53 (m, 3H, Ar), 7.87(d,
J = 7.5 Hz, 2H, Ar), 8.69 (s, 1H, NH); 13C NMR (75 MHz,
CDCl3): δC = 21.1, 37.5, 58.1, 126.4, 126.6, 128.8, 129.4,
131.4, 133.2, 137.0, 139.1, 151.1, 170.9 (CO); EI-MS: m/z
(%): 264 (100, M+), 235 (27), 173 (4), 145 (16), 119 (27),
104 (35), 77 (20); Anal. Calcd for C17H16N2O (264.13):
C 77.25, H 6.10, N 10.60 %. Found: C 76.81, H 6.04, N
10.60 %.
2‑Phenyl‑6‑(3,4,5‑trimethoxyphenyl)‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2k) Pale yellow solid, mp: 157–158 °C,
yield: 0.16 g (47 %). IR (KBr) (νmax, cm−1): 3,265 (NH),
1
1,690 (C = O), 1,647 (C = N); H-NMR (300 MHZ,
CDCl3): δH = 2.62 (dd, J = 16.4, 13.2 Hz, 1H, CHCO),
2.86 (dd, J = 16.5, 5.1 Hz, 1H, CHCO), 3.85 (s, 3H,
Me), 3.88 (s, 6H, Me), 4.88 (dd, J = 13.1, 5.0 Hz, 1H,
CHN), 6.69 (s, 2H, Ar), 7.46–7.57 (m, 3H, Ar), 7.87 (d,
J = 8.0 Hz, 2H, Ph), 8.69 (s, 1H, NH); 13C NMR (75 MHz,
CDCl3): δC = 37.7, 56.2, 58.6, 60.8, 103.6, 126.6, 128.9,
131.5, 133.1, 137.2, 138.0, 151.3, 153.45, 170.8 (CO);
EI-MS: m/z (%): 340 (100, M+), 325 (41), 311 (14), 297
(9), 221(14), 194 (12), 104 (57), 77 (21); Anal. Calcd for
C19H20N2O4 (340.14): C 67.05, H 5.92, N 8.23 %. Found:
C 66.85, H 5.65, N 8.48 %.
6‑([1,1′‑Biphenyl]‑4‑yl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2h) White solid, mp: 252–254 °C, yield:
0.231 g (71 %). IR (KBr) (νmax, cm−1): 3,257 (NH), 1,690
(C = O), 1,638 (C = N); H-NMR (300 MHZ, CDCl3):
1
δH = 2.67 (dd, J = 16.5, 12.4 Hz, 1H, CHCO), 2.93
(dd, J = 16.5, 5.4 Hz, 1H, CHCO), 5.04 (dd, J = 12.4,
5.3 Hz, 1H, CHN), 7.33-7.38 (m, 1H, Ar), 7.42–7.64 (m,
11H, Ar), 7.88 (dd, J = 6.6, 1.6 Hz, 2H, Ar), 8.41 (s, 1H,
NH); 13C NMR (75 MHz, CDCl3): δC = 37.1, 57.2, 126.3,
126.6, 126.7, 126.8, 126.9, 127.8, 128.4, 130.4, 133.1,
139.1, 140.0, 141.5, 152.2, 170.3 (CO); EI-MS: m/z (%):
326 (35, M+), 297 (16), 180 (43), 165 (15), 152 (78),
104 (100), 77 (80); Anal. Calcd for C22H18N2O (326.14):
C 80.96, H 5.56, N 8.58 %. Found: C 80.92, H 5.30, N
8.64 %.
6‑(2‑Nitrophenyl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2l) Pale yellow solid, mp: 182–184 °C,
yield: 0.163 g (55 %). IR (KBr) (νmax, cm−1): 3,362 (NH),
1,699 (C = O), 1,654 (C = N); 1H-NMR (300 MHZ, CDCl3):
δH = 2.52 (dd, J = 16.2, 14.3 Hz, 1H, CHCO), 3.12 (dd,
J = 16.5, 4.8 Hz, 1H, CHCO), 5.52 (dd, J = 13.9, 4.8 Hz,
1H, CHN), 7.45–7.55 (m, 4H, Ar), 7.67 (t, J = 7.6 Hz, 1H,
Ar), 7.84 (d, J = 7.8 Hz, 1H, Ar), 7.89 (d, J = 7.7 Hz, 2H,
Ar), 7.98 (d, J = 8.1 Hz, 1H, Ar), 9.65 (s, 1H, NH); 13C
NMR (75 MHz, CDCl3): δC = 36.8, 55.3, 124.6, 126.7,
6‑(4‑Methoxyphenyl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2i) White solid, mp: 157–159 °C, yield:
0.205 g (73 %). IR (KBr) (νmax, cm−1): 3,200 (NH), 1,704
1
(C = O), 1,653 (C = N); H-NMR (300 MHZ, CDCl3):
δH = 2.45 (dd, J = 16.5, 12.2 Hz, 1H, CHCO), 2.98 (dd,
J = 16.5, 5.9 Hz, 1H, CHCO), 3.87 (s, 3H, Me), 5.32 (dd,
J = 12.1, 5.4 Hz, 1H, CHN), 6.92 (d, J = 8.2 Hz, 1H, Ar),
7.01 (t, J = 7.6, 1H, Ar), 7.25–7.32 (m, 1H, Ar), 7.45-7.58
(m, 4H, Ar), 7.93 (d, J = 5.7 Hz, 2H, Ar), 9.31 (s, 1H, NH);
13C NMR (75 MHz, CDCl3): δC = 35.9, 53.2, 55.3, 110.3,
126.7, 128.4, 128.8, 130.5, 131.2, 133.4, 151.6, 156.3,
171.9; EI-MS: m/z (%): 280 (100, M+), 265 (34), 251
(24), 173 (12), 134 (19), 104 (75), 77 (40); Anal. Calcd for
C17H16N2O2 (280.12): C 72.84, H 5.75, N 9.99 %. Found: C
73.08, H 5.67, N 10.15 %.
Scheme 1 Preparation of dihydropyrimidin-4(3H)-one derivatives
2a–n
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J IRAN CHEM SOC
Table 1 Isolated yields obtained for 2a–n
Entry
Aldehyde
product
Yield (%)
73
1
1a
2a
2
80
1b
2b
3
40
1c
2c
4
70
1d
2d
5
52
1e
2e
6
7
88
53
1f
2f
1g
2g
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J IRAN CHEM SOC
Table 1 continued
8
71
73
63
1h
2h
9
1i
2i
10
1j
2j
11
47
1k
2k
12
13
14
55
57
54
1l
2l
1m
1n
2m
2n
128.3, 128.9, 129.9, 131.6, 132.8, 133.8, 138.1, 148.2,
152.2, 170.9; EI-MS: m/z (%): 296 (4, M++1), 278 (12),
247 (43), 220 (24), 147 (100), 104 (94), 77 (51);Anal. Calcd
for C16H13N3O3 (295.10): C 65.08, H 4.44, N 14.23 %.
Found: C 64.75, H 4.20, N 14.24 %.
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Scheme 2 Mechanistic rationalization for the formation of compound 2a–n
6‑(3‑Nitrophenyl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2m) Pale yellow solid, mp: 196–198 °C,
yield: 0.170 g (57 %). IR (KBr) (νmax, cm−1): 3,215 (NH),
1,691 (C = O), 1,641 (C = N); 1H-NMR (300 MHZ, CDCl3):
δH = 2.59 (dd, J = 16.2, 13.8 Hz, 1H, CHCO), 2.93 (dd,
J = 16.5, 5.1 Hz, 1H, CHCO), 5.06 (dd, J = 13.8, 5.1 Hz,
1H, CHN), 7.48–7.61 (m, 4H, Ar), 7.83 (d, J = 7.5 Hz, 1H,
Ar), 7.91 (d, J = 7.2 Hz, 2H, Ar), 8.19 (d, J = 8.1 Hz, 1H,
Ar), 8.41 (s, 1H, Ar), 8.98 (s, 1H, NH); 13C NMR (75 MHz,
CDCl3): δC = 37.3, 57.7, 121.9, 122.5, 126.6, 129.0, 129.7,
131.8, 132.7, 132.8, 144.5, 148.6, 152.2, 170.2 (CO);
EI-MS: m/z (%): 296 (76, M++1), 278 (4), 248 (4), 220 (2),
173 (10), 104 (100), 77 (38); Anal. Calcd for C16H13N3O3
(295.10): C 65.08, H 4.44, N 14.23 %. Found: C 64.92, H
4.28, N 14.23 %.
Results and discussion
Reaction of Meldrum’s acid with benzamidine hydrochloride
and benzaldehyde 1a‑n in EtOH in the presence of Et3N at
reflux over 1 h afforded 2a‑n (Scheme 1; Table 1). The struc-
tures of products were deduced by elemental analysis, MS,
IR, 1H NMR, and 13C NMR spectroscopy. For example, the
mass spectra of 2f displayed the molecular ion peak at 284
for M+ ([35Cl]) and 286 for M+ ([37Cl]) consistent with the
molecular structure. The IR spectrum of 2a displayed char-
acteristic absorption bands at 3,220 and 1,696 cm−1 due to
1
N–H and C = O stretching vibrations, respectively. The H
NMR spectrum of 2a showed three doublet of doublets at δ
2.56 (J = 16.5, 12.8 Hz, 1H), 2.86 (J = 16.5, 5.2 Hz, 1H),
4.95 (J = 12.8, 5.2 Hz, 1H) and one singlet at δ 8.47 (1H)
due to the CHC = O, CHC = O, CHN and NH protons,
respectively. Moreover, the 13C NMR spectrum of 2a dis-
played 12 distinct signals including one appearing at δ 170.2
for C = O carbon, consistent with molecular structure.
As illustrated in Table 1, aliphatic or a range of electron-
donating or electron-withdrawing substituted aromatic
aldehydes are tolerated in these one-pot three-component
reactions.
6‑(2‑Chlorophenyl)‑2‑phenyl‑5,6‑dihydropyrimi‑
din‑4(3H)‑one (2n) White solid, mp: 176–178 °C, yield:
0.154 (54 %). IR (KBr) (νmax, cm−1): 3,268 (NH), 1,695
1
(C = O), 1,638 (C = N); H-NMR (300 MHZ, CDCl3):
δH = 2.56 (dd, J = 16.5, 13.1 Hz, 1H, CHCO), 2.85 (dd,
J = 16.5, 5.2 Hz, 1H, CHCO), 4.92 (dd, J = 13.1, 5.2 Hz,
1H, CHN), 7.27–7.34 (m, 3H, Ar), 7.45–7.57 (m, 4H, Ar),
7.90 (d, J = 6.7 Hz, 2H, Ar), 9.27 (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): δC = 37.4, 57.8, 124.8, 126.7, 126.9,
127.6, 128.9, 130.0, 131.6, 132.9, 134.6, 144.3, 151.9,
171.0 (CO); EI-MS: m/z (%): 286 (5, M+ [37Cl]), 284 (100,
M+, [35Cl]), 255 (20), 249 (12), 227 (9), 138 (19), 104 (96),
77 (43); Anal. Calcd for C16H13ClN2O (284.07): C 67.49, H
4.60, N 9.84 %. Found: C 67.37, H 4.30, N 9.85 %.
Although the precise mechanism is not known, a mech-
anistic postulate as shown in Scheme 2 may be invoked
to rationalize the formation of 2a‑n. It is conceivable
that the in situ generated Knoevenagel adducts I1 under-
goes Michael addition by the liberated free benzamidine,
affording the intermediate I2. The β-ketoacid I3 interme-
diate is subsequently generated via attack of the second
1 3

J IRAN CHEM SOC
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Conclusion
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In conclusion, we have described a convenient route to
novel 5,6-dihydropyrimidin-4(3H)-one derivatives from
Meldrum’s acid, aldehydes and benzamidine in EtOH. The
5,6-dihydropyrimidin-4(3H)-ones reported in this work
broaden the scaffolds that are accessible through MCRs
and seem to be of potential interest for drug discovery. The
advantages of the present procedure are short reaction time,
mild reaction condition, use of simple experimental proce-
dure and prompt isolation of the products with generation
of interesting heterocycles in one-pot transformation.
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32. J.V. dos Anjos, F.J.B. Mendonça Jr, J.H. Costa-Silva, I.A. de
Acknowledgments The authors acknowledge the University of
Tehran for financial support of this research.
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1 3