Amino-functionalized MCM-41 base-catalyzed one-pot synthesis of 2-amino-5,6-dihydropyrimidin-4(3H)-ones

Article abstract of DOI:10.1007/bf03246225

A simple and efficient one-pot method for the preparation of 2-amino-5,6-dihydropyrimidin-4(3H)-one from the cyclocondensation of Meldrum's acid, aldehydes and guanidinium carbonate using a catalytic amount of amino-functionalized MCM-41 is described. Thi

Full text of DOI:10.1007/bf03246225

J. Iran. Chem. Soc., Vol. 8, No. 1, March 2011, pp. 280-286.
JOUIRrNaAnLiaOnF THE
Chemical Society
Amino-Functionalized MCM-41 Base-Catalyzed One-Pot Synthesis of 2-Amino-5,6-
dihydropyrimidin-4(3H)-ones
M. Mirza-Aghayana,*, T. Baie Lashakia, M. Rahimifarda, R. Boukherroubb and A.A. Tarlania
aChemistry and Chemical Engineering Research Center of Iran (CCERCI), P. O. BOX 14335-186, Tehran, Iran
bInstitut de Recherche Interdisciplinaire (IRI, USR 3078), Parc de la Haute Borne, 50 Avenue de Halley - BP 70478,
59658 Villeneuve d'Ascq and Institut d’Electronique, de Microélectronique et de Nanotechnologie (IEMN, UMR
8520), Cité Scientifique, Avenue Poincaré - B.P 60069, 59652 Villeneuve d’Ascq, France
(Received 10 April 2010, Accepted 14 August 2010)
A simple and efficient one-pot method for the preparation of 2-amino-5,6-dihydropyrimidin-4(3H)-one from the
cyclocondensation of Meldrum's acid, aldehydes and guanidinium carbonate using a catalytic amount of amino-functionalized
MCM-41 is described. This efficient technique has the advantage of giving 2-NH2-DHPM building blocks using a base catalyst in
good to high yields, being completed in short reaction times and offering a simple product isolation procedure.
Keywords: 2-Amino-5,6-dihydropyrimidin-4(3H)-one, Guanidinium carbonate, 2-NH2-DHPM building blocks, Base catalyst,
Amino-functionalized MCM-41
INTRODUCTION
However, three-component condensation of carbonyl
compounds, aldehydes and guanidine with base catalysts
leading to DHPMs has been reported by only few researchers
in few examples in the literature [18-23]. For example,
Milcent et al. [21] synthesized ethyl 2-amino-4-aryl-1,4-
dihydro-6-phenylpyrimidine-5-carboxylates from ethyl 3-aryl-
2-benzoylpropenoates and guanidine in DMF in the presence
of sodium hydrogen carbonate. The reaction required long
times (8 to 48 h) and gave modest yields (40%). Eynde et al.
[22] investigated the synthesis of the same compounds from
condensation of ethyl benzoylacetate, aldehyde and guanidine
in higher yields under similar conditions. On the other hand,
Ostras et al. described the synthesis of 2-NH2-DHPM building
blocks under conventional and microwave conditions from
three-component reaction of Meldrum's acid, aldehyde and
guanidine in moderate yields [23].
Dihydropyrimidines are well-known heterocycles that
display a diverse range of biological activities such as
antibacterial, antiviral, antitumor, anti-inflammatory and
antihypertensive as well as calcium channel blockers, α-1a-
antagonists, and neuropeptide Y (NPY) antagonists [1-3].
Consequently, the Biginelli reaction of carbonyl compounds,
aldehydes and urea or thiourea has been reviewed and several
improved procedures have recently been reported [3-9]. The
use of a number of homogeneous catalysts, such as
polyphosphate esters [10], BF3.OEt2 [11], LaCl3.H2O [12] and
InBr3 [13], and heterogeneous solid catalysts, such as HY [14],
Amberlyst-15 or Nafion-H [15], montmorillonite-KSF [16],
MCM-41-R-SO3H [17] and MCM-41 supported FeCl3 [8] has
been investigated in connection with this reaction.
It is of great practical importance to synthesize 2-NH2-
DHPM building blocks using easily separable and reusable
*Corresponding author. E-mail: m.mirzaaghayan@ccerci.ac.ir

Mirza-Aghayan et al.
solid base catalysts. MCM-41 is a highly porous material with
transform infrared (FTIR) spectra were recorded from KBr
disks using a Bruker Vector 22 FT-IR spectrometer. Elemental
analyses were performed on a ThermoFinigan Flash EA 1112
series elemental analyzer.
KF/Al2O3 (40% by weight) was prepared as follows: KF (3
g) was dissolved in water (20 ml), mixed with neutral TLC
grade chromatographic alumina (4.5 g) in water (20 ml), and
then stirred for 30 min at room temperature. After evaporation
of water under reduced pressure, the alumina was dried at 160
°C for 8 h.
MCM-41 was synthesized according to a previously
reported procedure [37] and functionalized with 3-amino-
propyltriethoxysilane (APTES) [38-39]. In a typical reaction,
1 g of MCM-41 was suspended in 50 ml of toluene and the
mixture was stirred for an hour and then to this mixture 1.5 g
of APTES was added and refluxed overnight. The white solid
was removed from the solvent by filtration and was soxhleted
by toluene and dried overnight under reduced pressure at 70
°C [26].
nano-size channel diameter (1.5-10 nm). It displays acidic
silanol groups and high surface area [24-25]. In earlier studies
by some of us on the chemical functionalization of MCM-41
catalyst with 3-aminopropyltriethoxysilane (APTES), we
observed a change in the surface properties [26]. NH2-
functionalized MCM-41 was prepared by means of chemical
bonding of aminosilane on the inner surface of the
mesoporous material. Elemental analyses (CHN) indicated
that the amine was immobilized on the surface and BET
surface area measurement revealed that the MCM-41 surface
area (1018 m2 g-1) decreased to 638 m2 g-1 after grafting
APTES molecules. Low-angle XRD pattern was slightly
shifted to higher angles, which is in agreement with a decrease
of the pore size [26]. This functionalization process converts
the surface to be basic by incorporation of NH2 terminal
groups and thus offers an opportunity to be used as a base
catalyst [27]. It should be noted that this water-tolerant [28-29]
amino-functionalized MCM-41 catalyst attracts reagents to the
surface quite easily, as compared to the hydrophilic surface of
MCM-41 [30-31].
In continuation of our investigations on the synthesis of
1,4-dihydropyridines (DHPs) [32] and dihydropyrimidines
(DHPMs) [33-35], herein we describe a simple and efficient
method for the preparation of 2-amino-5,6-dihydropyrimidin-
4(3H)-one building blocks using amino-functionalized MCM-
41 catalyst. In this work, we introduce an efficient three-
component reaction of Meldrum's acid, aldehydes and
guanidinium carbonate that provides an easy access to 2-
amino-5,6-dihydropyrimidin-4(3H)-one building blocks using
MCM-41 catalyst functionalized with 3-aminopropyltriethoxy-
silane (MCM-41-NH2) [26]. This efficient method has the
advantage of giving 2-NH2-DHPM building blocks in good to
high yields and being completed in short reaction times using
a base catalyst (MCM-41-NH2).
Typical Procedure for the Synthesis of 2-Amino-5,6-
dihydropyrimidin-4(3H)-one 4a-k Derivatives
To a solution of Meldrum's acid 1 (1 mmol), aldehyde 2a-
k (1 mmol) and guanidinium carbonate 3 (1 mmol) in DMF
(0.5 ml) was added amino-functionalized MCM-41 (10
mol%). The reaction mixture was heated at 120 °C for
appropriate time as indicated in Table 2. After completion of
the reaction, the mixture was poured into crushed ice while
stirring, filtered through a sintered funnel and washed by ethyl
acetate-hexane (1:3).
For further purification, the product was recrystallized
from ethanol. Spectroscopic data for the compounds 4a-k:
2-Amino-6-phenyl-5,6-dihydropyrimidin-4(3H)-one
1
(4a) [23]. m.p.: 257.3 °C; H NMR (DMSO-d6, 400 MHz): δ
2.27 (dd, J = 15.4, 8.3 Hz, 1H, CH2), 2.49 (dd, J = 15.4, 6.0
Hz, 1H, CH2), 4.61 (t, J = 7.5 Hz, 1H, CH), 6.54 (s, 2H, NH2),
7.25-7.35 (m, 5H, 5CH arom.), 7.63 (s, 1H, NH); MS (70 eV):
m/z (%) 189 (70) (M+), 188 (45), 160 (25), 146 (37), 104
(100); IR (KBr): ν 3319, 3221, 3005, 2970, 2899, 2796, 1641,
1597, 1556, 1510, 1487, 1375 cm-1, Anal. Calcd. for
C10H11N3O: C, 63.48; H, 5.86; N, 22.21%. Found: C, 62.43;
H, 5.97; N, 22.88%.
EXPERIMENTAL
Chemicals and Apparatus
Melting points were determined in evacuated capillaries
with a Buchi B-545 apparatus. Mass spectra were obtained on
a FISONS GC 8000/TRIO 1000 under 70 eV. 1H NMR
spectra were recorded on a Bruker 500, 400 or 80 MHz in
DMSO-d6 using tetramethylsilane as internal standard. Fourier
2-Amino-6-(4-chlorophenyl)-5,6-dihydropyrimidin-4
1
(3H)-one (4b). m.p.: 280.3 °C; H NMR (DMSO-d6, 400
281

Amino-Functionalized MCM-41 Base-Catalyzed One-Pot Synthesis
m/z (%) 219 (80) (M+), 218 (54), 204 (10), 190 (30), 176 (50),
134 (100); IR (KBr): ν 3367, 3232, 3012, 2835, 1651, 1589,
1550, 1498 cm-1; Anal. Calcd. for C11H13N3O2: C, 60.26; H,
5.98; N, 19.17%: Found: C, 59.71; H, 6.22; N, 19.25%.
2-Amino-6-(2-methoxyphenyl)-5,6-dihydropyrimidin-
MHz): δ 2.24 (dd, J = 15.4, 8.0 Hz, 1H, CH2), 2.49 (dd, J =
15.4, 6.0 Hz, 1H, CH2), 4.63 (t, J = 6.0 Hz, 1H, CH), 6.55 (s,
2H, NH2), 7.30 (d, J = 8.0 Hz, 2H, 2CH arom.), 7.40 (d, J =
8.0 Hz, 2H, 2CH arom.), 7.65 (s, 1H, NH); MS (70 eV): m/z
(%) 223 (30) (M+), 188 (20), 180 (20), 166 (5), 138 (40),
111(35); IR (KBr): ν 3356, 3008, 2837, 1639, 1591, 1506,
1398 cm-1; Anal. Calcd. for C10H10ClN3O: C, 53.70; H, 4.51;
N, 18.79%. Found: C, 53.31; H, 4.58; N, 18.48%.
1
4(3H)-one (4g) [23]. m.p.: 251.5 °C; H NMR (DMSO-d6, 80
MHz): δ 2.34 (m, 1H, CH2), 2.60 (m, 1H, CH2), 3.79 (s, 3H,
OCH3), 4.85 (t, J = 6.5 Hz, 1H, CH), 6.52 (s, 2H, NH2), 7.00-
7.27 (m, 5H, 4CH arom. and 1NH); MS (70 eV): m/z (%) 219
(100) (M+), 218 (100), 204 (85), 190 (35), 176 (90), 134 (75);
IR (KBr): ν 3336, 3000, 2835, 1664, 1627, 1598, 1570 cm-1;
Anal. Calcd. for C11H13N3O2: C, 60.26; H, 5.98; N, 19.17%.
Found: C, 59.28; H, 6.14; N, 19.24%.
2-Amino-6-(biphenyl-4-yl)-5,6-dihydropyrimidin-4
(3H)-one (4h). m.p.: 314.2 °C; 1H NMR (DMSO-d6, 80
MHz): δ 2.40 (m, 2H, CH2), 4.68 (t, J = 8.0 Hz, 1H, CH), 6.48
(s, 2H, NH2), 7.33-7.70 (m, 10H, 9CH arom., and 1NH); MS
(70 eV): m/z (%) 265 (100) (M+), 236 (35), 222 (27), 180 (75),
152 (65); IR (KBr): ν 3340, 3259, 3026, 1641, 1591, 1546,
1494, 1398 cm-1; Anal. Calcd. for C16H15N3O: C, 72.43; H,
5.70; N, 15.84%. Found: C, 71.39; H, 5.66; N, 15.80%.
2-Amino-6-(naphthalen-1-yl)-5,6-dihydropyrimidin-4
(3H)-one (4i). m.p.: 203.4 °C; 1H NMR (DMSO-d6, 80 MHz):
δ 2.25 (m, 1H, CH2), 2.60 (m, 1H, CH2), 5.50 (t, J = 6.5 Hz,
1H, CH), 6.50 (s, 2H, NH2), 7.42-8.20 (m, 8H, 7CH arom.,
and 1NH); MS (70 eV): m/z (%) 239 (20) (M+), 210 (25), 196
(40), 181 (100), 178 (25), 126 (40); IR (KBr): ν 3410, 3325,
3061, 2968, 2910, 1653, 1602, 1571, 1496, 1357 cm-1; Anal.
Calcd. for C14H13N3O: C, 70.28; H, 5.48; N, 17.56. Found: C,
71.29; H, 5.56; N, 17.01%.
2-Amino-6-(4-bromophenyl)-5,6-dihydropyrimidin-4
1
(3H)-one (4c) [23]. m.p.: 285.2 °C; H NMR (DMSO-d6, 400
MHz): δ 2.24 (dd, J = 15.0, 7.6 Hz, 1H, CH2), 2.47 (dd, J =
15.0, 6.0 Hz, 1H, CH2), 4.61 (t, J = 6.0 Hz, 1H, CH), 6.51 (s,
2H, NH2), 7.23 (d, J = 7.6 Hz, 2H, 2CH arom.), 7.53 (d, J =
7.6 Hz, 2H, 2CH arom.), 7.63 (s, 1H, NH); MS (70 eV): m/z
(%) 269 (15) (M++2), 267 (15) (M+), 240 (8), 224 (10), 196
(4), 188 (25), 182 (20); IR (KBr): ν 3358, 3005, 1901, 1616,
1556, 1487, 1375 cm-1; Anal. Calcd. for C10H10BrN3O: C,
44.80; H, 3.76; N, 15.67%. Found: C, 44.49; H, 3.78; N,
15.13%.
2-Amino-6-(4-methylphenyl)-5,6-dihydropyrimidin-4
(3H)-one (4d). m.p.: 264.1 °C; 1H NMR (DMSO-d6, 80
MHz): δ 2.16 (s, 3H, CH3), 2.36 (m, 2H, CH2), 4.56 (t, J = 7.2
Hz, 1H, CH), 6.59 (s, 2H, NH2), 7.15 (s, 4H, 4CH arom.), 7.60
(s, 1H, NH); MS (70 eV): m/z (%) 203 (70) (M+), 188 (25),
174 (30), 160 (80), 118 (100); IR (KBr): ν 3354, 3022, 2860,
1639, 1589, 1406, 1375 cm-1; Anal. Calcd. for C11H13N3O: C,
65.01; H, 6.45; N, 20.68. Found: C, 64.13; H, 6.36; N,
20.29%.
2-Amino-6-(4-methoxyphenyl)-5,6-dihydropyrimidin-4
1
(3H)-one (4e) [23]. m.p.: 275.8 °C; H NMR (DMSO-d6, 500
MHz): δ 2.25 (dd, J = 15.0, 9.0 Hz, 1H, CH2), 2.40 (dd, J =
15.5, 6.0 Hz, 1H, CH2), 3.70 (s, 3H, OCH3), 4.53 (t, J = 6.5
Hz, 1H, CH), 6.42 (s, 2H, NH2), 6.88 (d, J = 8.2 Hz, 2H, 2CH
arom.), 7.20 (d, J = 8.2 Hz, 2H, 2CH arom.), 7.49 (s, 1H, NH);
MS (70 eV): m/z (%) 219 (75) (M+), 218 (54), 204 (10), 190
(30), 176 (50), 134 (100); IR (KBr): ν 3356, 3032, 2829, 1637,
1560, 1377 cm-1; Anal. Calcd. for C11H13N3O2: C, 60.26; H,
5.98; N, 19.17%. Found: C, 59.65; H, 6.05; N, 18.71%.
2-Amino-6-(3-methoxyphenyl)-5,6-dihydropyrimidin-4
(3H)-one (4f). m.p.: 262.0 °C; 1H NMR (DMSO-d6, 80 MHz):
δ 2.07 (m, 1H, CH2), 2.38 (m, 1H, CH2), 3.71 (s, 3H, OCH3),
4.58 (t, J = 6.5 Hz, 1H, CH), 6.42 (s, 2H, NH2), 6.88 (m, 3H,
3CH arom.), 7.20 (m, 2H, 1CH arom., and 1NH); MS (70 eV):
2-Amino-6-(4-(dimethylamino)phenyl)-5,6-dihydro-
pyrimidin-4(3H)-one (4j) [23]. m.p.: 266.2 °C; 1H NMR
(DMSO-d6, 80 MHz): δ 2.40 (m, 2H, CH2), 2.85 (s, 6H,
2CH3), 4.48 (t, J = 8.0 Hz, 1H, CH), 6.42 (s, 2H, NH2), 6.67
(d, J = 8.8 Hz, 2H, 2CH arom.), 7.11 (d, J = 8.8 Hz, 2H, 2CH
arom.), 7.47 (s, 1H, NH); MS (70 eV): m/z (%) 232 (30) (M+),
203 (15), 189 (20), 147 (100), 131 (35); IR (KBr): ν 3425,
3034, 2968, 2885, 1654, 1620, 1560, 1521, 1402, 1369 cm-1;
Anal. Calcd. for C12H16N4O: C, 62.05; H, 6.94; N, 24.12%.
Found: C, 61.16; H, 6.91; N, 24.17%.
2-Amino-6-heptyl-5,6-dihydropyrimidin-4(3H)-one
1
(4k). m.p.: 249.2 °C; H NMR (DMSO-d6, 500 MHz): δ 0.84
(t, J = 6.8, 3H, CH3), 1.24 (m, 10H, 5CH2), 1.37 (m, 2H, CH2),
282

Mirza-Aghayan et al.
1.96 (dd, J = 15.4, 9.0 Hz, 1H, CH2), 2.26 (dd, J = 15.4, 5.5
corresponding
2-amino-5,6-dihydropyrimidin-4(3H)-one
Hz, 1H, CH2), 3.47 (m, 1H, CH), 6.22 (s, 2H, NH2), 7.23 (s, H,
NH), MS (70 eV): m/z (%) 211 (10) (M+), 182 (5), 168 (10),
154 (5), 140 (5), 126 (20), 112 (100); IR (KBr): ν 3317, 3012,
2920, 2852, 1656, 1500, 1379, 1325, 1215, 1170 cm-1; Anal.
Calcd. for C11H21N3O: C, 62.52; H, 10.02; N, 19.89%. Found:
C, 61.76; H, 9.91; N, 19.96%.
building blocks (Scheme 1).
The use of Meldrum's acid for the synthesis of fused
dihydropyridine-2-ones [36] and 2-NH2-DHPM building
blocks was previously described to take place in moderate
yields [23]. For example, 4e was obtained in 55 and 38% yield
by conventional and microwave protocols, respectively [23].
At earlier stages of our work, we investigated the influence
of solvent and temperature on the reaction yield of an
equimolar quantity of 4-methoxybenzaldehyde 2e, Meldrum's
acid 1 and guanidinium carbonate 3, as indicated in Table 1,
by examining different catalysts. KF/Al2O3, K2CO3 and
RESULTS AND DISCUSSION
A
three-component reaction of Meldrum's acid 1,
aldehydes 2a-k and guanidinium carbonate 3 afforded the
R
O
NH
Amino-functionalized MCM-41
N
O
RCHO
DMF
H2N
NH2
O
O
O
N
H
NH2
1
4a-k
2a-k
3
Scheme 1. Three-component synthesis of 2-amino-5,6-dihydropyrimidin-4(3H)-one.
Table 1. Effects of the Catalyst Type, Solvent and Temperature on the Formation of 2-Amino-6-aryl-5,6-
dihydropyrimidin-4(3H)-one
Entry
Catalyst
Solvent
Temperature
(°C)
78
Product
Time
(h)
7
5
3.5
1
1
1
1
1
Yield
(%)a
55
65
65
72
50
57
72
86
86
86
85
1
2
3
4
5
6
7
8
KF/Al2O3
KF/Al2O3
K2CO3
EtOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
4e
4e
4e
4e
4e
4e
4e
4c
4c
4c
4c
120
120
120
70
100
120
120
120
MCM-41-NH2
MCM-41-NH2
MCM-41-NH2
MCM-41-NH2
MCM-41-NH2
MCM-41-NH2
MCM-41-NH2
MCM-41-NH2
b
b
c
d
9
1
1
1
10
11
120
120
aIsolated yield. Reaction conditions: Meldrum's acid (1 mmol), aldehyde (1 mmol), guanidinium carbonate
(1 mmol), KF/Al2O3 40% by weight (1.2 g, 0.8 mmol) or K2CO3 (1 mmol) or MCM-41-NH2 (10 mol%). b100
mol% of MCM-41-NH2 was used. cSecond run. dThird run.
283

Amino-Functionalized MCM-41 Base-Catalyzed One-Pot Synthesis
MCM-41-NH2 were used to explore the reaction scope. After
(entries 4-6, Table 1). The results clearly indicate that the
yields are better at 120 °C (entry 4, Table 1). Finding the
suitable temperature and solvent, the influence of the catalyst
concentration on the reaction yield was investigated. 2-NH2-
DHPM Building blocks 4c and 4e were obtained in 86 and
72% yield with a catalyst concentration of 100 and 10 mol%,
respectively (entries 4, 7-9 Table 1). Increasing the catalyst
concentration did not show any significant effect on the yield,
indicating that 10 mol% of MCM-41-NH2 is sufficient for this
reaction. This catalyst also showed excellent reusability
(entries 10 and 11, Table 1).
The optimal conditions were reached when the reaction of
an equimolar solution of the Meldrum's acid 1, aldehydes 2a-k
and guanidinium carbonate 3 in the presence of 10 mol% of
the catalyst MCM-41-NH2 took place at 120 °C in 0.5 ml of
DMF as the solvent. Under these conditions, various
aldehydes (2a-k) reacted smoothly to give the corresponding
2-amino-5,6-dihydropyrimidin-4(3H)-one derivatives (4a-k)
after 1 h in 60-90% yield. The results in Table 2 show that the
MCM-41-NH2 base catalyst can be used in the synthesis of 2-
NH2-DHPM building blocks with various aldehydes in high
yields and short reaction times.
the time indicated in Table 1, the crude products were poured
into crushed ice while stirring, filtered through a sintered
funnel and washed by ethylacetate-hexane (1:3). For further
purification, the resulting products were recrystallized from
ethanol. The results are summarized in Table 1.
2-Amino-6-(4-methoxyphenyl)-5,6-dihydropyrimidin-4
(3H)-one 4e was obtained in 55% yield using KF/Al2O3 as a
catalyst in refluxing ethanol for 7 h (entry 1, Table 1). When
ethanol was replaced by DMF (0.5 ml) and the temperature
was raised to 120 °C, the yield increased to 65% and the
reaction time decreased to 5 h (entry 2, Table 1). The obtained
results indicate that 4e can be synthesized in good yields using
KF/Al2O3 or K2CO3 as catalysts in DMF at 120 °C, but the
reaction time was 5 and 3.5 h, respectively (entries 2 and 3,
Table 1). A rise in yield (72%) and a drop in the reaction time
(1 h) was observed when the amino-functionalized MCM-41
was used as catalyst in DMF at 120 °C (entry 4, Table 1). The
results suggest that amino-functionalized MCM-41 in DMF
can be used as an alternative catalyst. In order to find the
optimum temperature for the formation of the product 4e, the
occurrence of the reaction of Meldrum's acid 1, 4-
methoxybenzaldehyde 2e and guanidinium carbonate 3 was
monitored at three different temperatures (70, 100 and 120 °C)
Finally, a reasonable and appropriate mechanism is
suggested for this reaction, as outlined in Scheme 2. The
Table 2. Three-component Synthesis of 2-NH2-DHPM Building Blocks 4a-k from Meldrum's Acid 1, Aldehydes
2 and Guanidinium Carbonate 3 in the Presence of 10 mol% of Amino-functionalized MCM-41 Catalyst
Entry
R
Product
Time
(h)
1
1
1
1
1
1
1
1
1
1
1
Yield
(%)a
72
88
86
80
72
60
74
78
90
65
80
m.p. (°C)
Reported
257 [23]
Found
257.3
280.3
285.2
264.1
275.8
262.0
251.5
314.2
203.4
1
2
3
4
5
6
7
8
C6H5
p-Cl-C6H4
p-Br-C6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
-
275-276 [23]
-
278 [23]
-
206 [23]
-
-
p-CH3-C6H4
p-OCH3-C6H4
m-OCH3-C6H4
o-OCH3-C6H4
p-C6H5-C6H4
1-Naphthyl
p-(CH3)2N-C6H4
C7H15
9
10
11
4j
4k
266.2 261-262 [23]
249.2
-
aIsolated yield.
284

Mirza-Aghayan et al.
NH
NH
R
NH
Pathway A
R
O
H2N
NH2
+
H2
+
H
HO
N
NH2
H
N
NH2
O
-H2O
R
H
H
H
O
O
O
O
NH
O
R
O
O
R
Pathway B
H
O
H2N
NH2
O
N
O
O
+
-H2O
R
H
NH2
O
O
O
O
HN
O
(I)
cyclization
R
R
O
O
N
N
-CH3COCH3
-CO2
O
O
N
H
NH2
O
N
H
NH2
Scheme 2. The proposed reaction mechanism for the synthesis of 2-NH2-DHPM building blocks 4
reaction may proceed through the arylideneguanidinium
intermediate (formed in situ by the reaction of an aldehyde
with guanidine), and the subsequent addition of the enolate to
the arylideneguanidinium to generate the intermediate (I)
(Pathway A, Scheme 2). However, as was previously reported
[23], the reaction can proceed via pathway B to lead to the
formation of arylidene Meldrum's acid, which then undergoes
Michael addition of guanidine molecule to generate the
intermediate (I) (Pathway B, Scheme 2). The cyclization of
the intermediate (I) followed by its ring closure, elimination of
acetone and decarboxylation of the intermediate acid affords
the corresponding 2-NH2-DHPM building blocks (Scheme 2).
In summary, we have developed a convenient and efficient
alternative process for the synthesis of 2-amino-5,6-
dihydropyrimidin-4(3H)-one derivatives through a three-
component coupling of Meldrum's acid, aldehyde and
guanidinium carbonate using amino-functionalized MCM-41
as a basic catalyst. Amino-functionalized MCM-41 is a highly
promising environmentally-friendly base catalyst for the one-
pot synthesis of 2-amino-5,6-dihydropyrimidin-4(3H)-one
derivatives with high yields and short reaction times. The
technique offers simplicity of operation and easy work-up
procedure.
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